bluuebunny/crossref_metadata_2025 huggingface dataset:
Two common nonsynonymous paraoxonase 1 (PON1) gene polymorphisms and brain astrocytoma and meningioma
Authors: Martínez Carmen , Molina José A , Alonso-Navarro Hortensia , Jiménez-Jiménez Félix J , Agúndez José AG , García-Martín Elena
Published: August 2010

Background

Human serum paraoxonase 1 (PON1) plays a major role in the metabolism of several organophosphorus compounds. The enzyme is encoded by the polymorphic gene PON1, located on chromosome 7q21.3. Aiming to identify genetic variations related to the risk of developing brain tumors, we investigated the putative association between common nonsynonymous PON1 polymorphisms and the risk of developing astrocytoma and meningioma.

Methods

Seventy one consecutive patients with brain tumors (43 with astrocytoma grade II/III and 28 with meningioma) with ages ranging 21 to 76 years, and 220 healthy controls subjects were analyzed for the frequency of the nonsynonymous PON1 genotypes L55M rs854560 and Q192R rs662. All participants were adult Caucasian individuals recruited in the central area of Spain.

Results

The frequencies of the PON1 genotypes and allelic variants of the polymorphisms PON1 L55M and PON1 Q192R did not differ significantly between patients with astrocytoma and meningioma and controls. The minor allele frequencies were as follows: PON1 55L, 0.398, 0.328 and 0.286 for patients with astrocytoma, meningioma and control individuals, respectively; PON1 192R, 0.341, 0.362 and 0.302 for patients with astrocytoma, meningioma and control individuals, respectively. Correction for age, gender, or education, made no difference in odds ratios and the p values remained non-significant. Haplotype association analyses did not identify any significant association with the risk of developing astrocytoma or meningioma.

Conclusions

Common nonsynonymous PON1 polymorphisms are not related with the risk of developing astrocytoma and meningioma.
Genotypes and haplotypes of the VEGF gene and survival in locally advanced non-small cell lung cancer patients treated with chemoradiotherapy
Authors: Guan Xiaoxiang , Yin Ming , Wei Qingyi , Zhao Hui , Liu Zhensheng , Wang Li-E , Yuan Xianglin , O'Reilly Michael S , Komaki Ritsuko , Liao Zhongxing
Published: August 2010

Background

Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving in carcinogenesis, including lung cancer. We hypothesized that VEGF polymorphisms may affect survival outcomes among locally advanced non-small cell lung cancer (LA-NSCLC) patients.

Methods

We genotyped three potentially functional VEGF variants [-460 T > C (rs833061), -634 G > C (rs2010963), and +936 C > T (rs3025039)] and estimated haplotypes in 124 Caucasian patients with LA-NSCLC treated with definitive radiotherapy. We used Kaplan-Meier log-rank tests, and Cox proportional hazard models to evaluate the association between VEGF variants and overall survival (OS).

Results

Gender, Karnofsky's performance scores (KPS) and clinical stage seemed to influence the OS. The variant C genotypes were independently associated with significantly improved OS (CT+CC vs. TT: adjusted hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.37-0.92, P = 0.022), compared with the VEGF -460 TT genotype.

Conclusions

Our study suggests that VEGF -460 C genotypes may be associated with a better survival of LA-NSCLC patients after chemoradiotherapy. Large studies are needed to confirm our findings.
Human mammary fibroblasts stimulate invasion of breast cancer cells in a three-dimensional culture and increase stroma development in mouse xenografts
Authors: Olsen Charlotta J , Moreira José , Lukanidin Eugene M , Ambartsumian Noona S
Published: August 2010

Introduction

Tumour phenotype is regulated in a complex fashion as a result of interactions between malignant cells and the tumour stroma. Fibroblasts are the most abundant and perhaps most active part of the tumour stroma. A better understanding of the changes that occur in fibroblasts in response to the presence of malignant cells may lead to the development of new strategies for cancer treatment. We explored the effects of fibroblasts on the growth and invasion of mammary carcinoma tumour cells in vitro and in vivo.

Methods

In order to analyse secreted factors that affect invasive abilities of breast cancer cells we co-cultured human mammary fibroblasts (HMF3s) and cancer cells (MCF7S1) in three-dimensional (3D) growth conditions devoid of heterogeneous cell-cell contact. To study the possible influence of fibroblasts on MCF7S1 cancer cell growth in vivo we co-injected HMF3s and MCF7S1 cells in Balb/c nu/nu mice.

Results

In 3D co-culture both HMF3s and MCF7S1 cells demonstrated enhanced invasion into a Matrigel matrix. This was correlated with enhanced expression of the metastasis promoting S100A4 protein in fibroblasts, stimulation of the matrix metalloproteinase (MMP)-2 activity, and enhanced secretion of a range of different cytokines. Orthotopic injection of oestrogen-dependent MCF7S1 cancer cells together with fibroblasts showed stimulation of tumour growth in mice without an external oestrogen supply. The resulting tumours were characterized by increased development of extracellular matrix, as well as an increase of murine S100A4 concentration and activity of MMP-2 in the tumour interstitial fluid.

Conclusion

Stimulation of the invasive phenotype of tumour cells in 3D co-cultures with fibroblasts could be correlated with increased production of S100A4 and MMP-2. We propose that enhanced development of mouse host-derived tumour stroma in a MCF7S1 co-injection xenograft model leads to oestrogen independency and is triggered by the initial presence of human fibroblasts.
Antiproliferative effect of D-glucuronyl C5-epimerase in human breast cancer cells
Authors: Prudnikova Tatiana Y , Mostovich Liudmila A , Domanitskaya Natalia V , Pavlova Tatiana V , Kashuba Vladimir I , Zabarovsky Eugene R , Grigorieva Elvira V
Published: August 2010

Background

D-glucuronyl C5-epimerase (GLCE) is one of the key enzymes in the biosynthesis of heparansulfate proteoglycans. Down-regulation of GLCE expression in human breast tumours suggests a possible involvement of the gene in carcinogenesis. In this study, an effect of GLCE ectopic expression on cell proliferation and viability of breast carcinoma cells MCF7 in vitro and its potential molecular mechanisms were investigated.

Results

D-glucuronyl C5-epimerase expression was significantly decreased in MCF7 cells compared to normal human breast tissue. Re-expression of GLCE inhibited proliferative activity of MCF7 cells according to CyQUANT NF Cell Proliferation Assay, while it did not affect their viability in Colony Formation Test. According to Cancer PathFinder RT Profiler PCR Array, antiproliferative effect of GLCE in vitro could be related to the enhanced expression of tumour suppressor genes р53 (+3.3 fold), E2F1 (+3.00 fold), BRCA1 (+3.5 fold), SYK (+8.1 fold) and apoptosis-related genes BCL2 (+4.2 fold) and NFKB1 (+2.6 fold). Also, GLCE re-expression in MCF7 cells considerably changed the expression of some genes involved in angiogenesis (IL8, +4.6 fold; IFNB1, +3.9 fold; TNF, +4.6 fold and TGFB1, -5.7 fold) and invasion/metastasis (SYK, +8.1 fold; NME1, +3.96 fold; S100A4, -4.6 fold).

Conclusions

The ability of D-glucuronyl С5-epimerase to suppress proliferation of breast cancer cells MCF7 through the attenuated expression of different key genes involved in cell cycle regulation, angiogenesis and metastasis molecular pathways supports the idea on the involvement of the gene in regulation of breast cancer cell proliferation.
Cardiac and vascular changes in elderly atherosclerotic mice: the influence of gender
Authors: Pereira Thiago M. C. , Nogueira Breno V. , Lima Leandro C. F. , Porto Marcella L. , Arruda Jose A. , Vasquez Elisardo C. , Meyrelles Silvana S.
Published: August 2010

Background

Although advanced age is considered a risk factor for several diseases, the impact of gender on age-associated cardiovascular diseases, such as atherosclerotic processes and valvular diseases, remains not completely clarified. The present study was designed to assess aortic valve morphology and function and vascular damage in elderly using the apolipoprotein E knockout (ApoE KO) mouse. Our hypothesis was that advanced age-related cardiovascular changes are aggravated in atherosclerotic male mice.

Methods

The grade (0 to 4) of aortic regurgitation was evaluated through angiography. In addition, vascular lipid deposition and senescence were evaluated through histochemical analyses in aged male and female ApoE KO mice, and the results were compared to wild-type C57BL/6J (C57) mice.

Results

Aortic regurgitation was observed in 92% of the male ApoE KO mice and 100% of the male C57 mice. Comparatively, in age-matched female ApoE KO and C57 mice, aortic regurgitation was observed in a proportion of 58% and 53%, respectively. Histological analysis of the aorta showed an outward (positive) remodeling in ApoE KO mice (female: 1.86 ± 0.15; male: 1.89 ± 0.68) using C57 groups as reference values. Histochemical evaluation of the aorta showed lipid deposition and vascular senescence only in the ApoE KO group, which were more pronounced in male mice.

Conclusion

The data show that male gender contributes to the progression of aortic regurgitation and that hypercholesterolemia and male gender additively contribute to the occurrence of lipid deposition and vascular senescence in elderly mice.
Interleukin-27 acts on hepatic stellate cells and induces signal transducer and activator of transcription 1-dependent responses
Authors: Schoenherr Caroline , Weiskirchen Ralf , Haan Serge
Published: August 2010

Background

Interleukin (IL)-27 is a cytokine belonging to the IL-6/IL-12 cytokine family that is secreted by activated macrophages and dendritic cells and which strongly acts on T-cells and cells of the innate immune system. Not much is known about possible effects of IL-27 on other cell types. It signals via the common IL-6-type-cytokine receptor chain gp130 and the IL-27-specific chain WSX-1. We previously described that IL-27 also stimulates hepatoma cells and primary hepatocytes. The aim of this study was to investigate whether IL-27 would also act on hepatic stellate cells (HSC), the second most abundant hepatic cell type, which would demonstrate a more general role of this cytokine in the liver.

Results

Using a human HSC line and primary rat HSC we investigated the signalling characteristics of IL-27 in these cells. We show that IL-27 activates signal transducer and activator of transcription (STAT) 1 and to a minor extent STAT3 in a human HSC cell line and that it leads to the induction of STAT1 target genes such as interferon response factor-1, myxovirus resistance A and STAT1 itself. Similarly we find that IL-27 also elicits STAT1-dependent responses in primary rat HSC.

Conclusions

We provide the first evidence for a function of IL-27 in HSC and show that its responses resemble Interferon-γ-like functions in these cells. Our data suggests that IL-27 may play an important role in the context of liver inflammation by acting on the different liver cell types.
Detection of hepatitis B virus DNA among accepted blood donors in Nanjing, China
Authors: Liu Yong , Li Ping , Li Cuiping , Zhou Jinyong , Wu Chao , Zhou Yi-Hua
Published: August 2010

Background

Posttransfusion hepatitis B virus (HBV) infection still occurs although its incidence has been substantially reduced since the introduction of screening of hepatitis B surface antigen (HBsAg) in blood donors. This study aimed to investigate the occult HBV infection in accepted blood donors in Nanjing, China.

Results

The lower detection limit of the nested PCR in this study was estimated to be 20 copies/ml HBV DNA. The positive rate of occult HBV infection was 0.13% (5 of 2972) in the accepted blood donors. Sequencing data showed that the amplified HBV sequences were not identical each other and to the known sequences cloned in our laboratory, excluding the false-positive caused by cross-contamination. Phylogenetic analysis showed that the HBV in all five donors was genotype B; a single base deletion was detected in the S region of HBV DNA from one donor, and no mutation was observed in the "a" determinant of HBsAg from four other donors. All five donors were negative for anti-HBs and one was positive for anti-HBc.

Conclusions

The prevalence of occult HBV infection in the accepted blood donors in Nanjing, China is relatively high. The data would be meaningful in adapting strategy to eliminate posttransfusion HBV infection in China.
Fertility disorders and pregnancy complications in hairdressers - a systematic review
Authors: Peters Claudia , Harling Melanie , Dulon Madeleine , Schablon Anja , Torres Costa José , Nienhaus Albert
Published: August 2010

Background

Hairdressers often come into contact with various chemical substances which can be found in hair care products for washing, dyeing, bleaching, styling, spraying and perming. This exposure can impair health and may be present as skin and respiratory diseases. Effects on reproduction have long been discussed in the literature.

Method

A systematic review has been prepared in which publications from 1990 to 2010 were considered in order to specifically investigate the effects on fertility and pregnancy. The results of the studies were summarised separately in accordance with the type of study and the examined events.

Results

A total of 2 reviews and 26 original studies on fertility disorders and pregnancy complications in hairdressers were found in the relevant databases, as well as through hand searches of reference lists. Nineteen different outcomes concerning fertility and pregnancy are analysed in the 26 original studies. Most studies looked into malformation (n = 7), particularly orofacial cleft. Two of them found statistically significant increased risks compared to five that did not. Small for gestational age (SGA), low birth weight (LBW) and spontaneous abortions were frequently investigated but found different results. Taken together the studies are inconsistent, so that no clear statements on an association between the exposure as a hairdresser and the effect on reproduction are possible. The different authors describe increased risks of infertility, congenital malformations, SGA, LBW, cancer in childhood, as well as effects from single substances.

Conclusion

On the basis of the identified epidemiological studies, fertility disorders and pregnancy complications in hairdressers cannot be excluded. Although the evidence for these risks is low, further studies on reproductive risks in hairdressers should be performed as there is a high public health interest.
Acute left main coronary artery thrombosis due to cocaine use
Authors: Apostolakis Efstratios , Tsigkas Grigorios , Baikoussis Nikolaos G , Koniari Ioanna , Alexopoulos Dimitrios
Published: August 2010

It is common knowledge that cocaine has been linked to the development of various acute and chronic cardiovascular complications including acute coronary syndromes. We present a young, male patient, drug abuser who underwent CABG due to anterolateral myocardial infarction. Our presentation is one of the very rare cases reported in literature regarding acute thrombosis of left main coronary artery related to cocaine use, in a patient with normal coronary arteries, successfully operated. Drug-abusers seem to have increased mortality and morbidity after surgery and high possibility for stent thrombosis after percoutaneous coronary interventions, because of their usually terrible medical compliance and coexistent several problems of general health. There are no specific guidelines about treatment of thrombus formation in coronary arteries, as a consequence of cocaine use. So, any decision making concerning the final treatment of these patient is a unique and individualized approach. We strongly recommend that all these patients should be treated surgically, especially patients with thrombus into the left main artery.
Role of positron emission tomography-computed tomography in bronchial mucoepidermoid carcinomas: a case series and review of the literature
Authors: Jindal Tarun , Kumar Arvind , Kumar Rakesh , Dutta Roman , Meena Monika
Published: August 2010

Introduction

Mucoepidermoid carcinoma of the tracheobronchial tree is rare. Such tumors usually present with signs and symptoms of bronchial obstruction. Histologically, they can be classified as high-grade or low-grade tumors. Experience of imaging these tumors with 18fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) is limited. We present three cases of this rare tumor, describe the functional imaging results, and review the available literature.

Case presentation

Three Caucasian patients, two men (21 and 24 years of age) and one woman (14 years of age), with bronchial masses were evaluated by us. All three patients were symptomatic, and underwent a thorough clinical examination, bronchoscopy and biopsy, plain computed tomography, 18F-FDG PET-CT and 68Gallium 1,4,7,10-Tetraazacyclododecane-NI,NII,NIII,NIIII,- tetra acetic acid (D) - Phel1-Tyr3-octreotide positron emission tomography-computed tomography (68Ga-DOTATOC PET-CT). 18F-FDG PET-CT revealed mild uptake in all three patients, whereas 68Ga-DOTATOC PET-CT revealed no significant uptake in any patient, making carcinoid tumor unlikely. Results of histopathological examination were consistent with low-grade mucoepidermoid carcinoma in all patients.

Conclusion

Our study reveals that functional imaging may be helpful in the initial investigation of patients with mucoepidermoid carcinoma. 18F-FDG PET-CT may have a prognostic relevance by predicting the histopathologic differentiation of the tumor.
Gene-knockdown in the honey bee mite Varroa destructor by a non-invasive approach: studies on a glutathione S-transferase
Authors: Campbell Ewan M , Budge Giles E , Bowman Alan S
Published: August 2010

Background

The parasitic mite Varroa destructor is considered the major pest of the European honey bee (Apis mellifera) and responsible for declines in honey bee populations worldwide. Exploiting the full potential of gene sequences becoming available for V. destructor requires adaptation of modern molecular biology approaches to this non-model organism. Using a mu-class glutathione S-transferase (Vd GST-mu1) as a candidate gene we investigated the feasibility of gene knockdown in V. destructor by double-stranded RNA-interference (dsRNAi).

Results

Intra-haemocoelic injection of dsRNA-Vd GST-mu1 resulted in 97% reduction in Vd GST-mu1 transcript levels 48 h post-injection compared to mites injected with a bolus of irrelevant dsRNA (LacZ). This gene suppression was maintained to, at least, 72 h. Total GST catalytic activity was reduced by 54% in Vd GST-mu1 gene knockdown mites demonstrating the knockdown was effective at the translation step as well as the transcription steps. Although near total gene knockdown was achieved by intra-haemocoelic injection, only half of such treated mites survived this traumatic method of dsRNA administration and less invasive methods were assessed. V. destructor immersed overnight in 0.9% NaCl solution containing dsRNA exhibited excellent reduction in Vd GST-mu1 transcript levels (87% compared to mites immersed in dsRNA-LacZ). Importantly, mites undergoing the immersion approach had greatly improved survival (75-80%) over 72 h, approaching that of mites not undergoing any treatment.

Conclusions

Our findings on V. destructor are the first report of gene knockdown in any mite species and demonstrate that the small size of such organisms is not a major impediment to applying gene knockdown approaches to the study of such parasitic pests. The immersion in dsRNA solution method provides an easy, inexpensive, relatively high throughput method of gene silencing suitable for studies in V. destructor, other small mites and immature stages of ticks.
Oncogenic role of the chromobox protein CBX7 in gastric cancer
Authors: Zhang Xiao-Wei , Zhang Li , Qin Wei , Yao Xiao-Hong , Zheng Lei-Zhen , Liu Xin , Li Jin , Guo Wei-Jian
Published: August 2010

Background

Chromobox 7 (CBX7) is a Polycomb family protein that extends the lifespan of normal human cells via downregulating the expression of INK4a/ARF tumor suppressor locus. It was found that CBX7 expression was upregulated in lymphoma, but downregulated in some other human malignancies. The role of CBX7 in most types of cancer is still not clear. The purpose of this study is to investigate the role of CBX7 in gastric cancer.

Methods

The expression of CBX7 and its potential target protein p16(INK4a) in gastric cancer cell lines and gastric tumors was assayed by Western blot analysis and immunohistochemistry(IHC). The correlations between CBX7 expression and p16(INK4a), clinicopathological characteristics, and prognosis were analyzed. Gastric cancer cell line SGC-7901 was transfected with CBX7 siRNA expressing plasmids, and the expression of various proteins was analyzed by Western blot analysis. Cellular senescence, anchorage independent growth, and cell migration assays were performed to determine the functional role of CBX7 in gastric cancer cells.

Results

CBX7 was found to be overexpressed in gastric cancer cell lines and gastric tumors. Overexpression of CBX7 in gastric cancer tissues correlated with patients' age, clinical stage and lymph node metastasis. Knockdown of CBX7 expression in gastric cancer cells led to increased cellular senescence, decreased cellular proliferation and migration ability, accompanied by upregulation of p16(INK4a).

Conclusions

CBX7 acts as an oncogene in the carcinogenesis and progression of gastric cancer, and it may regulate tumorigenesis, cell migration and cancer metastasis partially via p16(INK4a) regulatory pathway.
Molecular apocrine differentiation is a common feature of breast cancer in patients with germline PTEN mutations
Authors: Banneau Guillaume , Guedj Mickaël , MacGrogan Gaëtan , de Mascarel Isabelle , Velasco Valerie , Schiappa Renaud , Bonadona Valerie , David Albert , Dugast Catherine , Gilbert-Dussardier Brigitte , Ingster Olivier , Vabres Pierre , Caux Frederic , de Reynies Aurelien , Iggo Richard , Sevenet Nicolas , Bonnet Françoise , Longy Michel
Published: August 2010

Introduction

Breast carcinoma is the main malignant tumor occurring in patients with Cowden disease, a cancer-prone syndrome caused by germline mutation of the tumor suppressor gene PTEN characterized by the occurrence throughout life of hyperplastic, hamartomatous and malignant growths affecting various organs. The absence of known histological features for breast cancer arising in a PTEN-mutant background prompted us to explore them for potential new markers.

Methods

We first performed a microarray study of three tumors from patients with Cowden disease in the context of a transcriptomic study of 74 familial breast cancers. A subsequent histological and immunohistochemical study including 12 additional cases of Cowden disease breast carcinomas was performed to confirm the microarray data.

Results

Unsupervised clustering of the 74 familial tumors followed the intrinsic gene classification of breast cancer except for a group of five tumors that included the three Cowden tumors. The gene expression profile of the Cowden tumors shows considerable overlap with that of a breast cancer subgroup known as molecular apocrine breast carcinoma, which is suspected to have increased androgenic signaling and shows frequent ERBB2 amplification in sporadic tumors. The histological and immunohistochemical study showed that several cases had apocrine histological features and expressed GGT1, which is a potential new marker for apocrine breast carcinoma.

Conclusions

These data suggest that activation of the ERBB2-PI3K-AKT pathway by loss of PTEN at early stages of tumorigenesis promotes the formation of breast tumors with apocrine features.
Human protein C concentrate in the treatment of purpura fulminans: a retrospective analysis of safety and outcome in 94 pediatric patients
Authors: Veldman Alex , Fischer Doris , Wong Flora Y , Kreuz Wolfhart , Sasse Michael , Eberspächer Bruno , Mansmann Ulrich , Schosser Rudolf
Published: August 2010

Introduction

Purpura fulminans (PF) is a devastating complication of uncontrolled systemic inflammation, associated with high incidence of amputations, skin grafts and death. In this study, we aimed to clarify the clinical profile of pediatric patients with PF who improved with protein C (PC) treatment, explore treatment effects and safety, and to refine the prognostic significance of protein C plasma levels.

Methods

In Germany, patients receiving protein C concentrate (Ceprotin®, Baxter AG, Vienna, Austria) are registered. The database was used to locate all pediatric patients with PF treated with PC from 2002 to 2005 for this national, retrospective, multi-centered study.

Results

Complete datasets were acquired in 94 patients, treated in 46 centers with human, non-activated protein C concentrate for purpura fulminans. PC was given for 2 days (median, range 1-24 days) with a median daily dose of 100 IU/kg. Plasma protein C levels increased from a median of 27% to a median of 71% under treatment. 22.3% of patients died, 77.7% survived to discharge. Skin grafts were required in 9.6%, amputations in 5.3%. PF recovered or improved in 79.8%, remained unchanged in 13.8% and deteriorated in 6.4%. Four adverse events occurred in 3 patients, none classified as severe. Non-survivors had lower protein C plasma levels (P < 0.05) and higher prevalence of coagulopathy at admission (P < 0.01). Time between admission and start of PC substitution was longer in patients who died compared to survivors (P = 0.03).

Conclusions

This retrospective dataset shows that, compared to historic controls, only few pediatric patients with PF under PC substitution needed dermatoplasty and/or amputations. Apart from epistaxis, no bleeding was observed. Although the data comes from a retrospective study, the evidence we present suggests that PC had a beneficial impact on the need for dermatoplasty and amputations, pointing to the potential value of carrying out a prospective randomised controlled trial.
SHIP negatively regulates Flt3L-derived dendritic cell generation and positively regulates MyD88-independent TLR-induced maturation
Authors: Antignano Frann , Ibaraki Mariko , Ruschmann Jens , Jagdeo Julienne , Krystal Gerald
Published: August 2010

SHIP plays an important role in the maturation and DC-induced Ag-specific T cell proliferation downstream of MyD88-independent signaling pathways in Flt3L-DCs.

We demonstrate herein that SHIP negatively regulates the proliferation, differentiation, and survival of FL-DCs from BM precursors, as shown by a more rapid appearance and higher numbers of CD11c+ DCs from SHIP−/− cultures as well as increased survival of mature FL-DCs in the absence of Flt3L. This increased survival, which is lost with low levels of the PI3K inhibitor, LY, correlates with an enhanced constitutive activation of the Akt pathway. Interestingly, however, these SHIP−/− FL-DCs display a less-mature phenotype after TLR ligand stimulation, as far as MHCII, CD40, and CD86 are concerned. Unexpectedly, SHIP−/− FL-DCs activated with TLR ligands, which use MyD88-independent pathways, are markedly impaired in their ability to stimulate Ag-specific T cell proliferation, and SHIP−/− FL-DCs activated by TLRs, which exclusively use the MyD88-dependent pathway, are as capable as WT FL-DCs. There is also a more pronounced TH1 skewing by the SHIP−/− FL-DCs than by WT FL-DCs, which is consistent with our finding that SHIP−/− FL-DCs secrete higher levels of IL-12 and TNF-α in response to LPS or dsRNA than their WT counterparts. These results suggest that SHIP negatively regulates FL-DC generation but positively regulates the maturation and function of FL-DCs induced by TLRs, which operate via MyD88-independent pathways.
Type 3 Deiodinase Deficiency Causes Spatial and Temporal Alterations in Brain T3 Signaling that Are Dissociated from Serum Thyroid Hormone Levels
Authors: Hernandez Arturo , Quignodon Laure , Martinez M. Elena , Flamant Frederic , St. Germain Donald L.
Published: August 2010

The type 3 deiodinase (D3) is an enzyme that inactivates thyroid hormones (TH) and is highly expressed during development and in the central nervous system. D3-deficient (D3KO) mice develop markedly elevated serum T3 level in the perinatal period. In adulthood, circulating T4 and T3 levels are reduced due to functional deficits in the thyroid axis and peripheral tissues (i.e. liver) show evidence of decreased TH action. Given the importance of TH for brain development, we aimed to assess TH action in the brain of D3KO mice at different developmental stages and determine to what extent it correlates with serum TH parameters. We used a transgenic mouse model (FINDT3) that expresses the reporter gene β-galactosidase (β-gal) in the central nervous system as a readout of local TH availability. Together with experiments determining expression levels of TH-regulated genes, our results show that after a state of thyrotoxicosis in early development, most regions of the D3KO brain show evidence of decreased TH action at weaning age. However, later in adulthood and in old age, the brain again manifests a thyrotoxic state, despite reduced serum TH levels. These region-specific changes in brain TH status during the life span of the animal provide novel insight into the important role of the D3 in the developing and adult brain. Our results suggest that, even if serum concentrations of TH are normal or low, impaired D3 activity may result in excessive TH action in multiple brain regions, with potential consequences of altered neural function that may be of clinical relevance to neurological and neuroendocrine disorders.
Association between Change in Body Composition and Change in Inflammatory Markers: An 11-Year Follow-Up in the Whitehall II Study
Authors: Fransson Eleonor I. , Batty G. David , Tabák Adam G. , Brunner Eric J. , Kumari Meena , Shipley Martin J. , Singh-Manoux Archana , Kivimäki Mika
Published: August 2010

Context: Obesity is associated with low-grade inflammation, but the long-term effects of weight change on inflammation are unknown.

Objective: The aim was to examine the association of change in weight, body mass index (BMI), and waist circumference with change in C-reactive protein (CRP) and IL-6 and to assess whether this association is modified by baseline obesity status.

Design and Setting: The design was a prospective cohort study among civil servants (the Whitehall II Study, UK). We used data from two clinical screenings carried out in 1991–1993 and 2002–2004 (mean follow-up, 11.3 yr).

Participants: We studied 2496 men and 1026 women [mean age, 49.4 (sd = 6.0) yr at baseline] with measurements on inflammatory markers and anthropometry at both baseline and follow-up.

Main Outcome Measures: We measured change in serum CRP and IL-6 during follow-up.

Results: The mean increases in CRP and IL-6 were 0.08 [95% confidence interval (CI), 0.07–0.09] mg/liter and 0.04 (95% CI, 0.03–0.05) pg/ml per 1-kg increase in body weight during follow-up. Study members with a BMI less than 25 kg/m2 at baseline had an average increase in CRP of 0.06 (95% CI, 0.05–0.08) mg/liter per 1-kg increase in body weight, whereas the increase in those who were overweight (25 ≤ BMI < 30 kg/m2) and obese (BMI ≥30 kg/m2) was greater: 0.08 (95% CI, 0.06–0.09) mg/liter and 0.11 (95% CI, 0.07–0.14) mg/liter, respectively (P value for interaction = 0.002). Similar patterns were observed for changes in BMI and waist circumference.

Conclusions: Those who were overweight or obese at baseline had a greater absolute increase in CRP per unit increase in weight, BMI, and waist circumference than people who were normal weight.
A Nested Case-Control Study of Midgestation Vitamin D Deficiency and Risk of Severe Preeclampsia
Authors: Baker Arthur M. , Haeri Sina , Camargo Carlos A. , Espinola Janice A. , Stuebe Alison M.
Published: August 2010

Context: Vitamin D may be important in the pathogenesis of severe preeclampsia. Given the few effective preventive strategies for severe preeclampsia, studies establishing this link are needed so that effective interventions can be developed.

Objective: Our objective was to assess whether midgestation vitamin D deficiency is associated with development of severe preeclampsia.

Design and Setting: We conducted a nested case-control study of pregnant women who had previously given blood for routine genetic multiple marker screening and subsequently delivered at a tertiary hospital between January 2004 and November 2008.

Patients: Participants included women with singleton pregnancies in the absence of any chronic medical illnesses. From an overall cohort of 3992 women, 51 cases of severe preeclampsia were matched by race/ethnicity with 204 women delivering at term with uncomplicated pregnancies. Banked maternal serum was used to measure maternal 25-hydroxyvitamin D [25(OH)D].

Main Outcome Measure: The main outcome was severe preeclampsia.

Results: Midgestation maternal 25(OH)D concentration was lower in women who subsequently developed severe preeclampsia compared with controls [median (interquartile range), 75 (47–107) nmol/liter vs. 98 (68–113) nmol/liter; P = 0.01]. Midgestation maternal 25(OH)D of less than 50 nmol/liter was associated with an almost 4-fold odds of severe preeclampsia (unadjusted odds ratio, 3.63; 95% confidence interval, 1.52–8.65) compared with midgestation levels of at least 75 nmol/liter. Adjustment for known confounders strengthened the observed association (adjusted odds ratio, 5.41; 95% confidence interval, 2.02–14.52).

Conclusion: Maternal midgestation vitamin D deficiency was associated with increased risk of severe preeclampsia. Vitamin D deficiency may be a modifiable risk factor for severe preeclampsia.
Dynamic characterization of a mechanical coupling for a rotating shaft
Authors: Tadeo A T , Cavalca K L , Brennan M J
Published: August 2010

This article concerns the dynamic characterization of a flexible coupling that connects two co-axial shafts. Four different lumped parameter coupling models from the literature are investigated to see which model could best predict the dynamic behaviour of the coupling. The finite-element method was used to model the rotor dynamic system incorporating the coupling. Frequency response functions from this model were compared with measured frequency response functions from the rotor test rig with the shaft and coupling rotating at a specific speed. Parameters from the model were adjusted to minimize an objective function involving the measured and predicted frequency response functions. It was found that the simplest model of the coupling that could reasonably represent the coupling involves rotational (bending) stiffness and damping.
Sequential linearization in analytical target cascading for optimization of complex multilevel systems
Authors: Chan K-Y
Published: August 2010

Large-scale design problems are high dimensional and deeply coupled in nature. The complexity of such large-scale systems prevents designers from solving them as a whole. Analytical target cascading (ATC) provides a systematic approach in solving decomposed large-scale systems that has solvable subsystems. By coordinating between subsystems, ATC can obtain the same optima as they were undecomposed. However, a convergent coordination requires series of ATC iterations that may hinder the efficiency of ATC. In this research, a sequential linearization technique is proposed to improve the efficiency of ATC. The proposed linearization technique is applied to each ATC iteration, and therefore each iteration has all linear subsystems that can be solved with high efficiency. The global convergence of this approach is ensured by a filter to determine the acceptance of the optima at each iteration and the corresponding trust region. One further motivation of the proposed strategy is its perceived potential in handling multilevel problems with random design variables. As previously studied, the sequential linear programming (SLP) algorithm provides a good balance between efficiency, accuracy, and convergence for single-level design optimization under random design variables. The proposed linearization technique can integrate with the SLP algorithm for multilevel systems. In this work, a geometric programming example is used to demonstrate the efficiency of the proposed method over standard ATC solution process without loss of accuracy.
A preliminary study of the load bearing capacity of a new foil thrust gas bearing
Authors: Chen R G , Zhou Q , Liu Y , Hou Y
Published: August 2010

With the rapid development of high-speed, oil-free turbomachinery, more and more attention is concentrated on compliant aerodynamic foil bearings. However, the common corrugated bump foil forming the compliant structure is so complicated that manufacturing it is time-consuming and troublesome. In this article, a simple type of aerodynamic foil thrust gas bearing with an elastic hemispherical convex dot support configuration is first proposed. Then experimental investigations on stability and its load capacity characteristic for this foil thrust bearing were conducted on a multi-functional thrust bearing test rig. The preliminary measurement and analysis are presented through the wave and spectrum of axial displacement response in the time and frequency domain. It is demonstrated that the proposed bearing can operate well and has good stability in tests, and experimental results show that the axial load can reach 25 N when the rotational speed is about 114 200 r/min.
Determination of Rail Vertical Profile through Inertial Methods
Authors: Real J , Salvador P , Montalbán L , Bueno M
Published: August 2010

Undergrounds and other metropolitan railway systems are characterized by their intense traffic, lasting up to 20 h per day, and so they need their maintenance work programmes to be optimized, implying an optimization of the monitoring processes. This article proposes an alternative to the traditional optical methods for monitoring rail profiles which can only be carried out by special vehicles. This is a new procedure that obtains the rail profile by means of inertial methods. The model this work is based on takes its input from the vertical accelerations produced in railway axles measured in trains running on regular services and calculates the rail irregularities that have originated them. The model uses the Fourier transform in order to solve the equations and find the transfer function that relates the input function and the output function in the frequency domain. The solution is then reverted into the time domain by applying the inverse Fourier transform. Data input comes from real measurements taken on line 9 of the Madrid underground, and the model's effectiveness was then analysed by comparing the output data with the rail profile taken using optical methods.
Investigation of the behaviour of selected ultrasonic guided wave modes to inspect rails for long-range testing and monitoring
Authors: Gharaibeh Y , Sanderson R , Mudge P , Ennaceur C , Balachandran W
Published: August 2010

Long-range ultrasonic testing (LRUT) uses guided waves in the kilohertz range to inspect many metres of an elongated component from a single point of access. This has considerable advantages for the rapid testing of long lengths for the detection of potentially harmful defects. This technique is well developed for structures that have a simple geometry, such as plates, rods, and pipes. However, this is a relatively new technology and there is still much to learn about the behaviour of guided waves and their application in complex structures, such as railway rails. The aim of this work was to identify suitable ultrasonic-guided wave modes that can detect common types of defects in each part of a rail (i.e. the head, web, and foot). The investigation was carried out using finite-element analysis and was validated experimentally. The findings of this research demonstrated the ability to detect transverse defects as small as 2 mm and 5 mm in the head and foot, respectively.
Comprehension and production of body part labels in 2‐ to 3‐year‐old children
Authors: Camões‐Costa Vera , Erjavec Mihela , Horne Pauline J.
Published: August 2010

This study examined which body part labels children could (i) produce when the experimenter touched different locations on her own body, asking each time ‘What's this?’ and (ii) comprehend by touching the correct locations on their own bodies in response to the experimenter asking ‘Where's the [body‐part label]?’. Seventeen children aged between 26 and 41 months, tested in a repeated measures procedure, were presented with 50 different body part stimuli in 200 test trials per child. Overall, the children produced fewer body part labels than they could comprehend. The accuracy of children's responses depended on (i) the location or extent of each body part (facial and broad body features were better known; joints and features in or attached to broad body parts the least well known); (ii) the amount of sensory (but not motor) representation each body part has in the human cortex; and (iii) whether a body part was commonly named by caregivers. These results present a precise mapping of the body parts that young children are able to name and locate on their own bodies in response to body part names; they suggest several possible determinants of lexical‐semantic body knowledge and add to the understanding of how it develops in childhood.
The devil is in the details: Judgments of responsibility and absenteeism from work
Authors: Patton Eric
Published: August 2010

This paper presents and tests a model suggesting that individual episodes of absenteeism, and the circumstances surrounding these events, are an important avenue for research and can help us understand the outcomes related to this behaviour. Through an experimental design using vignettes describing the absence of a co‐worker, this paper tests how reason for absence and context (i.e., work demands related to deadlines) surrounding an episode influences judgments of responsibility, emotional reactions, and behavioural intentions. The findings indicate that reasons for absence and context are important determinants of the reactions of others following an absence episode.
Design and synthesis of fluorescence-based siderophore sensor molecules for FeIII ion determination
Authors: Su Bao-Lian , Moniotte Nicolas , Nivarlet Noan , Tian Ge , Desmet Jonathan
Published: August 2010

The design principles of fluorescence-based siderophore sensor molecules for detection of heavy transition-metal (HTM) ions are first reviewed. As an example, fluorescein-desferrioxamine (FlDFO), a highly efficient fluorophore molecule combining a specific Fe ion receptor and a fluorescence-sensitive signalling site has been designed, synthesized, and used for dosing with Fe ions. Its response test shows its high selectivity and sensitivity to FeIII ions and its potential for nanobiosensor design. This work clearly identified that among two FlDFO positional isomers differing by the attachment of DFO at the 5- or 6-position of the bottom benzene ring of Fl, the fluorescence of 6-FlDFO is insensitive to the complexation with Fe ions. This is independent of the linkage used between Fl and DFO. Only 5-FlDFO could be a highly potential sensor molecule since it has been revealed that in a free state without complexation with Fe ions, this fluoroionophore sensor molecule gave a maximum fluorescent signal. With successive Fe ion complexing, the fluorescence of 5-FlDFO decreased very sensitively and proportionally with ion concentration. The response speed has been evaluated as a function of Fe ion concentration. Responses to other metal ions present in the solution, such as Cu2+, Ca2+, Ni2+, and Al3+, and the effect of pH value on the efficiency of the sensor molecules have also been investigated.
To sleep perchance to sing: the suspension of disbelief in the prologue to Francesco Cavalli's Gli Amori d'Apollo e di Dafne (1640)
Authors: Wissner Reba
Published: August 2010

In the newly popularized genre of opera during the seventeenth century, the allegorical prologue was commonly used as a preface from about 1600 to 1670, with no fewer than 98 opera prologues composed throughout Venice during this period. These prologues, often sung by allegories and/or characters from myth, set the stage for the proceeding drama. In the prologue to Francesco Cavalli's 1640 operaGli Amori d'Apollo e di Dafne, its characters, the gods of sleep and dreams, set the stage for an opera that revolves around a dream. This article explores the act of wishing the audience peaceful and pleasant dreams by using oratory as a method that the allegorical figures use to sing the audience a lullaby. The purpose of this lullaby is to instigate the suspension of disbelief required to allow the story to gain the audience's credibility. This article will show how Cavalli's opera does so uniquely by spatially extending its effects outwards onto the audience rather than only onto the characters onstage.
Jazz musicality in postdramatic theatre and the opacity of auditory signs
Authors: Bouko Catherine
Published: August 2010

Lehmann's paradigm of postdramatic theatre has mainly been criticized on two levels: its flexibility and its alleged putting to death of drama. I wish to highlight to what extent flexible paradigms like the postdramatic one are necessary to study the numerous performances that are characterized by their in-between-ness between dramatic and postdramatic codes. The study of postdramatic jazz musicality that we observe in Jaz by Koffi Kwahul or inIsabella's Roomby Jan Lauwers demonstrates the need for such flexibility.

Lehmann's notion of independent auditory semiotics could be a relevant tool to study the exploitation of text as music (and not only in music). As Lehmann does not develop this concept but only mentions it in his general postdramatic theory, I wish to propose an introductory model of postdramatic auditory semiotics, based on the opacity of the theatrical sign and on the Peircian notion oficonic thought. The latter makes it possible to study performativity per se via semiotic theories. Consequently, in contrast to the opinion of many researchers, among whom is the semiotician Erika Fischer-Lichte, theatrical semiotics does not only provide tools to study what the signs of the performancemean. It can also deal with autonomous performativity, which is particularly necessary with regard to postdramatic theatre.
Eight Tips for Implementing New Technologies in Health Care
Authors: Wilson Katherine A. , Pavlas Davin , Sharit Joseph , Salas Eduardo
Published: August 2010

FEATURE AT A GLANCE: The use of new technologies to improve patient care is becoming increasingly common for the health care professional. However, these initiatives often fail be cause health care organizations lack sufficient guidance as to their implementation. New technologies often are deployed without careful consideration, and users are faced with the dilemma of relying on “band-aid” solutions for defective systems. The purpose of this article is to provide an initial, comprehensive resource intended to assist HF/E practitioners and other health care professionals in the selection and implementation of a new technology system in their organizations. We provide eight critical success factors to help guide the health care industry in such endeavors.