bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrotreating of light gas oil using carbon nanotube supported NiMoS catalysts: Kinetic modelling
Authors: Sigurdson S. , Dalai A. K. , Adjaye J.
Published: December 2010

Multi‐walled carbon nanotubes (MWCNTs) were applied as supports for NiMo hydroprocessing catalysts. Rate expressions were developed for an optimum NiMo/MWCNT catalyst to help predict its hydrodesulfurisation (HDS) and hydrodenitrogenation (HDN) activities while varying the operation parameters for coker light gas oil treatment. Power law models were best fit with reaction orders of 2.6 and 1.2, and activation energies of 161 and 82.3 kJ/mol, for the HDS and HDN reactions, respectively. Generalised Langmuir–Hinshelwood models were found to have reaction orders of 3.0 and 1.5, and activation energies of 155 and 42.3 kJ/mol, for the HDS and HDN reactions, respectively.

Étude des nanotubes de carbone multiparois (MWCNT) lorsqu'ils servent de supports aux catalyseurs d'hydrotraitement NiMo. Des expressions de vitesse ont été développées pour un catalyseur NiMo/MWCNT optimal pour prédire ses activités d'hydrodésulfurisation (HDS) et d'hydrodénitrogénation (HDN) tout en faisant varier les paramètres d'exploitation pour le traitement du gas‐oil léger de cokéfaction. Les modèles de loi de puissance sont les mieux adaptés avec des ordres de réaction de 2,6 et 1,2 et des énergies d'activation de 161 kJ/mol et 82,3 kJ/mol pour les réactions d'HDS et d'HDN respectivement. Les modèles généralisés de Langmuir–Hinshelwood ont des ordres de réaction de 3,0 et 1,5 et des énergies d'activation de 155 kJ/mol et 42,3 kJ/mol pour les réactions d'HDS et d'HDN respectivement. © 2010 Canadian Society for Chemical Engineering
Accelerating cardiac excitation spread simulations using graphics processing units
Authors: Rocha B. M. , Campos F. O. , Amorim R. M. , Plank G. , Santos R. W. dos , Liebmann M. , Haase G.
Published: December 2010

The modeling of the electrical activity of the heart is of great medical and scientific interest, because it provides a way to get a better understanding of the related biophysical phenomena, allows the development of new techniques for diagnoses and serves as a platform for drug tests. The cardiac electrophysiology may be simulated by solving a partial differential equation coupled to a system of ordinary differential equations describing the electrical behavior of the cell membrane. The numerical solution is, however, computationally demanding because of the fine temporal and spatial sampling required. The demand for real‐time high definition 3D graphics made the new graphic processing units (GPUs) a highly parallel, multithreaded, many‐core processor with tremendous computational horsepower. It makes the use of GPUs a promising alternative to simulate the electrical activity in the heart. The aim of this work is to study the performance of GPUs for solving the equations underlying the electrical activity in a simple cardiac tissue. In tests on 2D cardiac tissues with different cell models it is shown that the GPU implementation runs 20 times faster than a parallel CPU implementation running with 4 threads on a quad–core machine, parts of the code are even accelerated by a factor of 180. Copyright © 2010 John Wiley & Sons, Ltd.
Contextual environment and stakeholder perception of corporate social responsibility practices in uganda
Authors: Bagire Vincent Amooti , Tusiime Immaculate , Nalweyiso Grace , Kakooza John Bosco
Published: December 2010

The debate on dimensions of corporate social responsibility (CSR) is ongoing. This study was conducted to examine perceptions of stakeholders towards CSR activities in Uganda. The research was prompted by many questions from students undertaking a Business Administration course on the distinction between marketing activities and CSR. While many materials were locally available, none was explicit on stakeholder perceptions. The study used a cross‐sectional qualitative research design. Data was obtained from 119 questionnaires and 88 interviews. The results show that many companies are involved in various CSR activities. Key players were multinationals. The public awareness of CSR is high, but there is confusion as to what it is about. The process of CSR and the influence of contextual environment factors are puzzling. The flagship of CSR through advertisements has resulted in the public perceiving it more as marketing than philanthropy or ethical action. The study provided insights for further research in other contexts. Copyright © 2010 John Wiley & Sons, Ltd and ERP Environment.
ADAM‐8, a metalloproteinase, drives acute allergen‐induced airway inflammation
Authors: Paulissen Geneviève , Rocks Natacha , Guéders Maud M. , Bedoret Denis , Crahay Céline , Quesada‐Calvo Florence , Hacha Jonathan , Bekaert Sandrine , Desmet Christophe , Foidart Jean‐Michel , Bureau Fabrice , Noel Agnès , Cataldo Didier D.
Published: December 2010

Asthma is a complex disease linked to various pathophysiological events including the activity of proteinases. The multifunctional A disintegrin and metalloproteinases (ADAMs) displaying the ability to cleave membrane‐bound mediators or cytokines appear to be key mediators in various inflammatory processes. In the present study, we investigated ADAM‐8 expression and production in a mouse model of allergen‐induced airway inflammation. In allergen‐exposed animals, increased expression of ADAM‐8 was found in the lung parenchyma and in DC purified from the lungs. The potential role of ADAM‐8 in the development of allergen‐induced airway inflammation was further investigated by the use of an anti‐ADAM‐8 antibody and ADAM‐8 knockout animals. We observed a decrease in allergen‐induced acute inflammation both in BALF and the peribronchial area in anti‐ADAM‐8 antibody‐treated mice and in ADAM‐8‐deficient mice (ADAM‐8−/−) after allergen exposure. ADAM‐8 depletion led to a significant decrease of the CD11c+ lung DC. We also report lower levels of CCL11 and CCL22 production in antibody‐treated mice and ADAM‐8‐ deficient mice that might be explained by decreased eosinophilic inflammation and lower numbers of DC, respectively. In conclusion, ADAM‐8 appears to favour allergen‐induced acute airway inflammation by promoting DC recruitment and CCL11 and CCL22 production.
Hoxb8 conditionally immortalised macrophage lines model inflammatory monocytic cells with important similarity to dendritic cells
Authors: Rosas Marcela , Osorio Fabiola , Robinson Matthew J. , Davies Luke C. , Dierkes Nicola , Jones Simon A. , Reis e Sousa Caetano , Taylor Philip R.
Published: December 2010

We have examined the potential to generate bona fide macrophages (MØ) from conditionally immortalised murine bone marrow precursors. MØ can be derived from Hoxb8 conditionally immortalised macrophage precursor cell lines (MØP) using either M‐CSF or GM‐CSF. When differentiated in GM‐CSF (GM‐MØP) the resultant cells resemble GM‐CSF bone marrow‐derived dendritic cells (BMDC) in morphological phenotype, antigen phenotype and functional responses to microbial stimuli. In spite of this high similarity between the two cell types and the ability of GM‐MØP to effectively present antigen to a T‐cell hybridoma, these cells are comparatively poor at priming the expansion of IFN‐γ responses from naïve CD4+ T cells. The generation of MØP from transgenic or genetically aberrant mice provides an excellent opportunity to study the inflammatory role of GM‐MØP, and reduces the need for mouse colonies in many studies. Hence differentiation of conditionally immortalised MØPs in GM‐CSF represents a unique in vitro model of inflammatory monocyte‐like cells, with important differences from bone marrow‐derived dendritic cells, which will facilitate functional studies relating to the many ‘sub‐phenotypes’ of inflammatory monocytes.
γδ T cells develop, respond and survive – with a little help from CD27
Authors: Born Willi K. , O'Brien Rebecca L.
Published: December 2010

Although the TNF receptor family member CD27 has been known for some time, its functional role as a coreceptor on T and B cells remains poorly understood. Recent reports have shown that CD27 and its ligand CD70 play a critical role in the development and function of γδ T cells in mice. In this issue of the European Journal of Immunology, a study now extends these findings to the Vγ9Vδ2+ subset of human γδ T cells. This subset, whose responses are readily elicited by phosphoantigens, plays an important role in anti‐tumor immune responses. This study shows that most Vγ9Vδ2+ cells express CD27, and signaling via the CD27‐CD70 axis is needed for their survival, proliferation and cytokine secretion. Moreover, CD27 functions as a coreceptor, which promotes, in conjunction with TCR‐mediated signals, expansion of Th1‐biased Vγ9Vδ2+ cells. This new information underscores the significance of CD27 in γδ T‐cell functional differentiation, and is likely to facilitate the development of γδ T‐cell‐based clinical immunotherapy.
Conversion of Dibenzoxaphosphinines into 2‐Hydroxybiphenyl‐2′‐ylphosphane Ligands and Their BH3 Adducts: The O–Hδ+···Hδ––B Hydrogen–Hydrogen Bond
Authors: Wawrzyniak Piotr , Kindermann Markus K. , Heinicke Joachim W. , Jones Peter G.
Published: December 2010

Chlorodibenz[c,e][1,2]oxaphosphinine 1Cl reacted with bulky organolithium compounds R1Li (R1 = tBu, mesityl) under mild conditions to yield organodibenz[c,e][1,2]oxaphosphinines 1R1, which underwent ring‐opening metathesis with less bulky organolithium compounds R2Li. After O‐trimethylsilylation, 2‐(trimethylsilyloxy)biphenylylphosphanes 2 were isolated. Reaction of 1Cl with R2Li followed by silylation provided symmetrically P‐substituted compounds 2. The formation of compounds 3 and 4 demonstrated the facile hydrolysis and oxidation of 1R1, the formation of compound 5cox indicated the sensitivity of 2 to hydrolysis and air oxidation. Methanolysis of 2 provided the free hydroxybiphenylylphosphanes 5 (for further modification by O‐acylation), which were converted into air‐stable borane adducts 6. The latter were unable to undergo O‐acylation. Acylation of 5 followed by borane protection afforded O‐acyloxybiphenylylphosphane–borane adducts, as demonstrated by the formation of compounds 7a and 8a. X‐ray crystal structure analysesrevealed intermolecular O–H···H–B hydrogen–hydrogen bonds; for compound 6b the average H···H distance is 1.90 Å, whereas for 6e a three‐centre O–H···H2B interaction (av. H···H 2.25 Å) was observed, which is still shorter than twice the van der Waals radius for hydrogen (2.4 Å). To the best of our knowledge this is the first report on hydrogen–hydrogen bonds in functionally substituted phosphane–boranes and may explain the low reactivity at the OH group. Only on stronger heating was hydrogen evolved.
Application of Carbon Nanotube‐Modified Electrodes as Electrochemical Sensors for the Continuous Monitoring of 2,4‐Dichlorophenol
Authors: Arribas A. Sánchez , Moreno M. , Bermejo E. , Pérez J. A. , Román V. , Zapardiel A. , Chicharro M.
Published: December 2010

The use of glassy carbon electrodes (GCEs) modified with multiwalled carbon nanotube (CNT) films for the continuous monitoring of 2,4‐dichlorophenol (2,4DCP) in flow systems has been examined. The performance of these modified electrodes was evaluated and compared to bare GCE by cyclic voltammetry experiments and by flow injection analysis (FIA) with amperometric detection monitoring the response of 2,4DCP and 1,4‐benzoquinone in 0.050 M phosphate buffer pH 7.0. The CNT‐modified electrodes provided lower overpotentials, higher sensitivity and much higher signal stability under a dynamic regime than bare GCEs. The application of GCEs modified with a layer of CNT dispersed in Nafion for controlling 2,4DCP impurity in 2,4‐dichlorophenoxyacetic acid illustrates the possibilities of such electrodes for the stable long‐term measurements demanded by industrial activities.
Electrochemical Ochratoxin A Immunosensor System Developed on Sulfonated Polyaniline
Authors: Muchindu Munkombwe , Iwuoha Emmanuel , Pool Edmund , West Natasha , Jahed Nazeem , Baker Priscilla , Waryo Tesfaye , Williams Avril
Published: December 2010

An impedimetric immunosensor for ochratoxin A (OTA) composed of polyaniline‐polyvinyl sulfonate and anti‐OTA antibody on Pt disk electrode was produced, characterised and calibrated with its responses to standard OTA solutions at pH 7.2. The limit of detection and sensitivity of the OTA immunosensor were calculated to be 10 pg/kg and 563 kΩ L/ng, respectively. The European Commission limit for OTA in roasted coffee and cereals is 5 µg/kg. Application of the immunosensor to certified reference materials of roasted coffee, wheat and corn gave OTA concentrations of 2.5, 8.6 and 21.1 µg/kg, respectively. The result for corn compared favourably with ELISA results and vendor specifications.
Pitch control system design to improve frequency response capability of fixed‐speed wind turbine systems
Authors: Valsera‐Naranjo Eduardo , Sumper Andreas , Gomis‐Bellmunt Oriol , Junyent‐Ferré Adrià , Martínez‐Rojas Marcela
Published: December 2010

This paper describes a pitch control design method to deal with grid frequency deviations. The method is based on reserving a percentage of power extracted from the wind turbine. In order to validate the control method, simulations in a full power system have been carried out. The results show that the proposed pitch control can contribute to power stabilization. Copyright © 2010 John Wiley & Sons, Ltd.
A novel frequency offset estimation technique for Mobile WiMAX
Authors: Khairy Mohamed M.
Published: December 2010

In this paper, a novel frequency offset estimation technique for the OFDMA based WiMAX system is proposed. It is perceived that Mobile WiMAX based on the IEEE802.16e standard has an aperiodic preamble, hindering the most efficient frequency offset estimation techniques which are based on utilising the preamble's periodicity. In this paper, a novel technique for creating periodicity in the preamble by exploiting its design is proposed and evaluated. The results show that the proposed scheme has a significantly better performance than the currently used techniques. Copyright © 2010 John Wiley & Sons, Ltd.
Radial compression function for vector quantizer of Laplacian source with high dynamic variance range
Authors: Perić Zoran H. , Jovanović Aleksandra Ž.
Published: December 2010

In this paper, our aim is to define a high dynamic range vector quantization model for an i.i.d. Laplacian source. In order to do this we use a geometric approach and lattice quantization. As a result, we achieve symmetry in distribution of code vectors and introduce the radial scalar compression function for lattice cell side determination. This enables derivation of a sophisticated creation for a condition which the radial compression function should satisfy in order to make the SQNR non‐dependent on variance. It is interesting that the obtained solution represents the generalisation of solution in the case of high dynamic range scalar quantization. Because of that, in the second part of the paper, the well‐known semilogarithmicA‐law compression characteristic is utilized as radial scalar compression function of geometric vector quantizer. It is shown that such a model has very good performances over a very wide variance range. The proper choice of compression parameterAand dimensionnenables the constant SQNR to sustain over much wider variance range than in case of log‐scalar quantization. Particularly, the high dimension makes it possible to broaden the variance range over which SQNR remains constant by increasing theAvalue simultaneously holding the SQNR level unchanged. In comparison with the widely used log‐scalar quantization, the presented solution for dimensions from 10 to 140 gives a quality improvement of 7–9 dB, while comparison of maximal SQNR value to that of optimal scalar quantization shows the SQNR growth of 3–5 dB. Furthermore, for dimension 40 the SQNR maximum is only for 0.5 dB lower than that of optimal vector quantization, while dynamic range characteristic broadening is considerable. The cited benefits of high dynamic range vector quantization make it possible to realize a high quality signal compression. Besides, in comparison with the adaptive quantization, our proposal has a smaller implementation complexity. Copyright © 2010 John Wiley & Sons, Ltd.
Facile Preparation of an Excellent Pt/RuO2‐MnO2/CNTs Nanocatalyst for Anodes of Direct Methanol Fuel Cells
Authors: Zhou C. , Peng F. , Wang H. , Yu H. , Yang J. , Fu X.
Published: December 2010

RuO2‐MnO2 complex supported by multi‐wall carbon nanotubes (CNTs) was firstly synthesised by the oxidation–reduction precipitation of RuCl3 and KMnO4 in one step. Then Pt was loaded onto the obtained RuO2‐MnO2/CNTs to fabricate a novel anodic catalyst Pt/RuO2‐MnO2/CNTs for direct methanol fuel cells (DMFCs). The catalyst was characterised by transmission electron microscopy (TEM), X‐ray diffraction (XRD), temperature programmed reduction (TPR), X‐ray photoelectron spectroscopy (XPS) and BET specific surface areas (BET). Pt nanoparticles were found uniformly dispersed on the surface of CNTs, with the average diameter of about 2.0 nm. The activities of methanol and CO electrocatalytic oxidation were analysed, and the reaction mechanism of methanol electro‐oxidation on Pt/RuO2‐MnO2/CNTs catalyst was discussed. The MnO2 in the catalysts improves the proton conductivity and electrochemical active surface area (EAS) for the catalysts. RuO2 improves the CO oxidation activity and Pt dispersion. CNTs provide effectively electron channels. Thus, the Pt/RuO2‐MnO2/CNTs catalyst has high utilisation of the noble metal Pt, high CO oxidation ability and excellent methanol electro‐oxidation activity, being an outstanding anode catalyst for DMFC.
Management of the clinically negative neck in early‐stage head and neck cancers after transoral resection
Authors: Rodrigo Juan P. , Shah Jatin P. , Silver Carl E. , Medina Jesus E. , Takes Robert P. , Robbins K. Thomas , Rinaldo Alessandra , Werner Jochen A. , Ferlito Alfio
Published: December 2010

The decision regarding treatment of the clinically negative neck has been debated extensively. This is particularly true with early‐stage tumors for which surgery is the treatment of choice, and the tumor has been resected transorally without a cervical incision. Elective neck dissection in this situation is an additional procedure with potential associated morbidity. The alternative strategy for the clinically negative neck is to “wait and watch.” Both an elective neck dissection policy and a “watchful waiting” policy have their proponents. The purpose of this article was for us to review the literature about this subject to try to answer the following question: if the tumor has been resected transorally, should an elective treatment of the neck be performed or is a “watchful waiting” policy safe and adequate? We conclude that, currently, the best available evidence suggests that elective neck dissection does not seem to be superior to the policy of observation without neck surgery, with regard to survival and control of neck disease. This review highlights the need for further well‐designed prospective studies that will provide more reliable answers to the debatable issue of the management of the clinically negative neck in such cases. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
BMI1'S maintenance of the proliferative capacity of laryngeal cancer stem cells
Authors: Chen Hui , Zhou Liang , Dou Tonghai , Wan Guanglun , Tang Huiqing , Tian Jie
Published: December 2010

Background

In laryngeal squamous cell carcinoma (SCC), CD133+ cells were found to display cancer stem cell (CSC) characteristics. BMI1 is an oncogene that plays key roles in proliferation in CSCs. However, no published reports have examined the role of BMI1 in laryngeal CSCs.

Methods

Immunofluorescence staining confirmed the coexpression of BMI1 and CD133. After sorting, real‐time polymerase chain reaction (PCR) revealed BMI1 was differentially expressed in CD133+ cells. BMI1 was knocked down and proliferation, colony formation, and apoptosis assays were performed. The influence on CD133+ cells was determined by flow cytometry, sphere‐formation assay, and quantitative PCR. Tumorigenicity assays were performed, and the impact on related genes was evaluated.

Results

BMI1 was highly enriched in CD133+ cells. BMI1 maintained CD133+ cell proliferation and prevented apoptosis. Gene expression analysis suggested BMI1 regulated alternate cellular pathways.

Conclusion

BMI1 was required to maintain the proliferative capacity of laryngeal CSCs, which may be a molecular target to cure patients with laryngeal SCC. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Gender-Specific Differences in Adipose Distribution and Adipocytokines Influence Adolescent Nonalcoholic Fatty Liver Disease Δ
Authors: Ayonrinde Oyekoya T. , Olynyk John K. , Beilin Lawrence J. , Mori Trevor A. , Pennell Craig E. , de Klerk Nicholas , Oddy Wendy H. , Shipman Peter , Adams Leon A.
Published: December 2010

Nonalcoholic fatty liver disease (NAFLD) is a predominantly adult-diagnosed disorder. Knowledge regarding the epidemiology, phenotype, and metabolic risk factors, during adolescence is limited. We sought to determine the prevalence, phenotype, and predictors of NAFLD in 1170 community-based adolescents in the Western Australian Pregnancy Cohort (Raine) Study (the Raine Cohort) who underwent a cross-sectional assessment that included questionnaires, anthropometry, cardiovascular examinations, blood tests, and abdominal ultrasound examinations. Among the 1170 adolescents assessed, the prevalence of NAFLD was 12.8%. Females compared with males had a significantly higher prevalence of NAFLD (16.3% versus 10.1%,

P

= 0.004) and central obesity (33.2% versus 9.9%,

P

< 0.05). The severity of hepatic steatosis was associated with the body mass index, waist circumference, subcutaneous adipose tissue thickness (SAT), serum leptin level, homeostasis model assessment for insulin resistance score (

P

< 0.001 for all), and serum alanine aminotransferase level (

P

< 0.005) in both genders, but it was associated with increasing visceral adipose tissue thickness (VAT;

P

< 0.001) and decreasing serum adiponectin levels (

P

< 0.05) in males alone. Males and females with NAFLD had similar amounts of SAT (

P

> 0.05); however, in comparison with females with NAFLD, males with NAFLD had greater VAT, a more severe metabolic phenotype with higher glucose levels and systolic blood pressure and lower adiponectin and high-density lipoprotein cholesterol levels (

P

< 0.001 for all), and greater measures of liver injury (alanine aminotransferase and aspartate aminotransferase,

P

< 0.001 for all). Similarly, metabolic syndrome was more common in males than females with NAFLD (24% versus 8%,'

P

= 0.01). Suprailiac skinfold thickness predicted NAFLD independently of the body mass index, insulin resistance, and VAT.

Conclusion:

Gender differences in adolescent NAFLD are related to differences in adipose distribution and adipocytokines. The male phenotype of NAFLD is associated with more adverse metabolic features and greater visceral adiposity than the female phenotype despite the lower prevalence of NAFLD. (Hepatology 2011;)
Seeing old friends from a different angle: Novel properties of hematopoietic growth factors in the healthy and diseased brain
Authors: Diederich Kai , Schäbitz Wolf‐Rüdiger , Minnerup Jens
Published: December 2010

Hematopoietic growth factors are known for their bolstering effects on the growth, survival, and differentiation of blood progenitor cells. Several of these cytokines also influence the proliferation of neural stem/progenitor cells, paralleling cellular mechanisms in analogy to their function in the hematopoietic system. Erythropoietin (EPO), granulocyte‐colony stimulating factor (G‐CSF), thrombopoietin (TPO), and their respective receptors are all expressed in the hippocampus of the mammalian brain. Recent studies have confirmed EPO and G‐CSF as vital neurotrophic and neuroprotective factors, and ascertained their role in neuroprotection and neuroregeneration as pertaining to the most prominent neurodegenerative diseases. The aims of this review are to discuss newly discovered properties of G‐CSF, EPO, and TPO beyond their known functions in the hematopoietic system, to create an overview of the accumulating data on the role of these factors in hippocampal function, and to highlight any potential clinical implications. © 2010 Wiley Periodicals, Inc.
Calpain‐1 expression is associated with relapse‐free survival in breast cancer patients treated with trastuzumab following adjuvant chemotherapy
Authors: Storr Sarah J. , Woolston Caroline M. , Barros Fabricio F.T. , Green Andrew R. , Shehata Mohamed , Chan Stephen Y. , Ellis Ian O. , Martin Stewart G.
Published: December 2010

The calpain family, and their endogenous inhibitor calpastatin, has been implicated in cancer progression, and recent in vitro data have indicated a role in trastuzumab resistance. The aims of our study were to examine expression levels of calpastatin, calpain‐1 and calpain‐2 in breast tumours from patients treated with trastuzumab following adjuvant chemotherapy to determine their potential as biomarkers to predict therapeutic response. The expression of calpastatin, calpain‐1 and calpain‐2 was determined, using immunohistochemistry (IHC), in tumours from a series of 93 patients with primary breast cancer treated with surgery and adjuvant chemotherapy with or without trastuzumab followed by trastuzumab to complete 1 year of therapy. IHC was performed using tissue microarrays constructed from cores taken from intratumour and peripheral tumour areas. Expression was correlated with clinicopathologic variables and patient outcome. Calpastatin expression was correlated with Nottingham prognostic index (p = 0.003) and lymph node status (p = 0.007). Trastuzumab resistance was defined as disease relapse during therapy. Calpain‐1 expression is associated with relapse‐free survival (p = 0.001) and remained significant in multivariate analysis accounting for confounding pathological and treatment variables (hazard ratio 4.60, 95% confidence interval 1.05–20.25; p = 0.043). Calpain‐1 may be a useful biomarker to predict relapse‐free survival in breast cancer patients treated with adjuvant trastuzumab and chemotherapy. A larger verification study is warranted.
Sequential Processes in Palladium‐Catalyzed Silicon‐Based Cross‐Coupling
Authors: Denmark Scott E. , Liu Jack Hung‐Chang
Published: December 2010

Although developed somewhat later, silicon‐based cross‐coupling has become a viable alternative to the more conventional Suzuki–Miyaura, Stille–Kosugi–Migita, and Negishi cross‐coupling reactions because of its broad substrate scope, high stability of silicon‐containing reagents, and low toxicity of waste streams. An empowering and yet underappreciated feature unique to silicon‐based cross‐coupling is the wide range of sequential processes available. In these processes, simple precursors are first converted to complex silicon‐containing cross‐coupling substrates, and the subsequent silicon‐based cross‐coupling reaction affords an even more highly functionalized product in a stereoselective fashion. In so doing, structurally simple and inexpensive starting materials are quickly transformed into value‐added and densely substituted products. Therefore, sequential processes are often useful in constructing the carbon backbones of natural products. In this review, studies of sequential processes involving silicon‐based cross‐coupling are discussed. Additionally, the total syntheses that utilize these sequential processes are also presented.
Determination of fentanyl, metabolite and analogs in urine by GC/MS
Authors: Strano‐Rossi Sabina , Álvarez Iván , Tabernero María Jesús , Cabarcos Pamela , Fernández Purificación , Bermejo Ana María
Published: December 2010

A rapid and sensitive method for the simultaneous determination of alfentanyl, sufentanyl and fentanyl (and its major metabolite norfentanyl) in urine was developed and validated. The method involved a liquid–liquid extraction in alkaline conditions, derivatization with pentafluoropropionic anhydride to improve the sensitivity for norfentanyl and subsequent analysis in GC/MS. The LODs are 0.08 ng ml−1 for all substances (0.04 ng ml−1 for alfentanyl). Intra‐ and inter‐day precision coefficient of variation was always below 15%; mean relative error (accuracy) was always below 15%. The method was linear for all analytes, with quadratic regression of calibration curves always higher than 0.99. The method was applied to real samples of subjects who had received therapeutic doses of fentanyl, showing its suitability for the determination of low levels of these substances. The method was also applied to a subject whose death was attributed to fentanyl overdose. Copyright © 2010 John Wiley & Sons, Ltd.
Genotoxic effects of (−)‐cubebin in somatic cells of mice
Authors: Maistro Edson Luis , Marcondes Natel André Vinicius , de Souza Gustavo Henrique Bianco , Perazzo Fábio Ferreira
Published: December 2010

(−)‐Cubebin belongs to the dibenzylbutyrolactone lignan group, which is widely distributed in the plant kingdom. Because this compound shows interesting biological activities, it is extremely important to evaluate its possible genotoxic activity to allow its safe use in humans. Thus, the present study was performed to investigate the genotoxicity potential activity of (−)‐cubebin assessed by two assays: micronucleus in bone marrow cells and comet test in peripheral blood leukocytes of Swiss mice. In the (−)‐cubebin dose range‐finding assays, the maximum tolerated dose was greater than 2000 mg kg−1. The compound was administered by an oral route at single doses of 250, 500 and 2000 mg kg−1 body weight. Cytotoxicity was assessed by scoring 200 consecutive total polychromatic (PCE) and normochromatic (NCE) erythrocytes (PCE/NCE ratio). Under our experimental conditions, micronucleus and comet assays, respectively, showed that (−)‐cubebin caused dose‐related clastogenic and genotoxic effects in the somatic cells investigated. PCE/NCE ratio showed no cytotoxicity for the three doses of the compound. The data suggest caution in the ingestion of (−)‐cubebin by humans, especially at high doses. Copyright © 2010 John Wiley & Sons, Ltd.
Adenylate cyclase and calmodulin-dependent kinase have opposite effects on osteoclastogenesis by regulating the PKA-NFATc1 pathway
Authors: Yoon Soo-Hyun , Ryu Ji yoon , Lee Youngkyun , Lee Zang Hee , Kim Hong-Hee
Published: December 2010

Nuclear factor of activated T cells c1 (NFATc1) is a transcription factor crucial for the differentiation of osteoclasts. In this study we discovered new signaling pathways involving cAMP regulators that modulate NFATc1 during osteoclastogenesis. The osteoclast differentiation factor receptor activator of NF-κB ligand (RANKL) increased the expression of adenylate cyclase 3 (AC3), accompanied by a rise in the intracellular cAMP level in osteoclasts. The knockdown of AC3 enhanced in vitro osteoclastogenesis and in vivo bone resorption, whereas cAMP-elevating agents showed opposite effects. The antiosteoclastogenic effect of the AC3-cAMP pathway was mediated by the inhibition of NFATc1 nuclear translocation and its autoamplification via a protein kinase A (PKA)–dependent mechanism. RANKL has been shown to activate Ca2+/calmodulin-dependent protein kinases (CaMKs). Knockdown or catalytic inhibition of CaMKs elevated intracellular cAMP levels in RANKL-treated osteoclast precursors and suppressed the activation of NFATc1. Taken together, our results demonstrate a pivotal role for the cAMP-PKA-NFATc1 signaling pathway during osteoclast differentiation, suggesting a mechanism by which osteoclastogenesis is fine-tuned by a balance between AC3 and CaMKs activities. © 2011 American Society for Bone and Mineral Research.
Control of RUNX3 by histone methyltransferases
Authors: Lee You Mie
Published: December 2010

Runt‐related (RUNX) family proteins function as context‐dependent transcription factors during developmental processes such as hematopoiesis, neurogenesis, and osteogenesis. RUNX3 is involved in a variety of physiological processes including neurogenesis, thymopoiesis, and dendritic cell maturation. A large amount of information indicates that RUNX3 may be a tumor suppressor. Recent data suggest that the molecular mechanism responsible for RUNX3 deficiency in numerous cancers is a primarily epigenetic silencing. The present review focuses on the regulation of RUNX3 gene expression by histone modification, emphasizing histone methylation at the RUNX3 promoter and inactivation of protein itself. Inactivation of the promoter and protein can be the results of various chemical modifications, including methylation by histone methyltransferase. Inactivation of RUNX3 may contribute to the tumor initiation, progression and pathogenesis in specific microenvironmental contexts. Finally, this review describes the reactivation of RUNX3 by epigenetic regulatory agents. J. Cell. Biochem. 112: 394–400, 2011. © 2010 Wiley‐Liss, Inc.
Associations of saposin C, Src, and androgen receptor upregulate the expression and function of androgen receptor in human prostate cancer cells
Authors: Ding Yan , Wang Xiaoling , Xu Aihui , Xu Xia , Tian Keli , Young Charles Y.F. , Yuan Huiqing
Published: December 2010

We previously demonstrated that ectopic expression of neurotrophic peptide (NP) derived from saposin C promotes androgen receptor (AR) expression and transactivation in human prostate cancer cells. This prompted us to investigate how NP or saposin C can function in cells. We constructed plasmids expressing saposin C or a chimeric peptide of a viral TAT transduction domain and saposin C (TAT‐saposin C) with His‐tag. Intracellular localization of saposin C and NP was predominantly shown in transfected cells, while TAT‐saposin C was detected around membrane and in cytosol by immunofluorescence staining. Furthermore, induction of the AR expression and activation of the AR transcriptional function were observed in cells transfected with saposin C or TAT‐saposin C, compared to control cells transfected with an empty plasmid. The effects of saposin C and TAT‐saposin C on AR activity were examined in the presence of inhibitors of GPCR, MAPK1/2, and PI3K/Akt. Interestingly, we found that these inhibitors only affect AR activities in cells with TAT‐saposin C expression but not with saposin C expression. Immunostaining images showed that co‐localization of saposin C, Src, and the AR occurred in transfected cells. Physical interactions of saposin C/NP, Src, and the AR were then demonstrated by co‐immunoprecipitation assays. Blockage of Src activity by specific inhibitor led to a decrease in the saposin C‐mediated enhancement of AR transactivity, suggesting that intracellular expression of saposin C caused stimulation of AR expression and activity by associations with Src in LNCaP cells. This effect may not be mediated by GPCR. J. Cell. Biochem. 112: 818–828, 2011. © 2010 Wiley‐Liss, Inc.
Coping Style
Authors: Beutler Larry E. , Harwood T. Mark , Kimpara Satoko , Verdirame David , Blau Kathy
Published: December 2010

The fit of patient coping style and psychotherapy focus has been suggested as improving treatment outcome. This article reviews the definitions, measures, and previous research surrounding this hypothesis. An original meta‐analysis of 12 carefully selected studies (N = 1,291 patients) resulted in a weighted, mean effect size (d) of .55 in favor of a fit between externalizing patients and symptom‐focused treatment or, alternatively, internalizing patients and insight‐focused treatment. This medium‐size effect indicates that nondiagnostic patient factors, like coping style, are important considerations in the selection of effective therapies. Clinical examples and clinical recommendations are provided. © 2010 Wiley Periodicals, Inc. J Clin Psychol: In Session 67:176–183, 2011.
An approximation to the temporal order in endogenous circadian rhythms of genes implicated in human adipose tissue metabolism
Authors: Garaulet Marta , Ordovás José M. , Gómez‐Abellán Purificación , Martínez Jose A. , Madrid Juan A.
Published: December 2010

Although it is well established that human adipose tissue (AT) shows circadian rhythmicity, published studies have been discussed as if tissues or systems showed only one or few circadian rhythms at a time. To provide an overall view of the internal temporal order of circadian rhythms in human AT including genes implicated in metabolic processes such as energy intake and expenditure, insulin resistance, adipocyte differentiation, dyslipidemia, and body fat distribution. Visceral and subcutaneous abdominal AT biopsies (n = 6) were obtained from morbid obese women (BMI ≥ 40 kg/m2). To investigate rhythmic expression pattern, AT explants were cultured during 24‐h and gene expression was analyzed at the following times: 08:00, 14:00, 20:00, 02:00 h using quantitative real‐time PCR. Clock genes, glucocorticoid metabolism‐related genes, leptin, adiponectin and their receptors were studied. Significant differences were found both in achrophases and relative‐amplitude among genes (P < 0.05). Amplitude of most genes rhythms was high (>30%). When interpreting the phase map of gene expression in both depots, data indicated that circadian rhythmicity of the genes studied followed a predictable physiological pattern, particularly for subcutaneous AT. Interesting are the relationships between adiponectin, leptin, and glucocorticoid metabolism‐related genes circadian profiles. Their metabolic significance is discussed. Visceral AT behaved in a different way than subcutaneous for most of the genes studied. For every gene, protein mRNA levels fluctuated during the day in synchrony with its receptors. We have provided an overall view of the internal temporal order of circadian rhythms in human adipose tissue. J. Cell. Physiol. 226: 2075–2080, 2011. © 2010 Wiley‐Liss, Inc.
BRG1 mutations found in human cancer cell lines inactivate Rb‐mediated cell‐cycle arrest
Authors: Bartlett Christopher , Orvis Tess J. , Rosson Gary S. , Weissman Bernard E.
Published: December 2010

Eukaryotic organisms package DNA into chromatin for compact storage in the cell nucleus. However, this process promotes transcriptional repression of genes. To overcome the transcriptional repression, chromatin remodeling complexes have evolved that alter the configuration of chromatin packaging of DNA into nucleosomes by histones. The SWI/SNF chromatin remodeling complex uses energy from ATP hydrolysis to reposition nucleosomes and make DNA accessible to transcription factors. Recent studies showing mutations of BRG1, one of two mutually exclusive ATPase subunits, in human tumor cell lines and primary tissue samples have implicated a role for its loss in cancer development. While most of the mutations lead to complete loss of BRG1 protein expression, others result in single amino acid substitutions. To better understand the role of these BRG1 point mutations in cancer development, we characterized SWI/SNF function in human tumor cell lines with these mutations in the absence of BRM expression, the other ATPase component. We found that the mutant BRG1 proteins still interacted with the core complex members and appeared at the promoters of target genes. However, while these mutations did not affect CD44 and CDH1 expression, known targets of the SWI/SNF complex, they did abrogate Rb‐mediated cell‐cycle arrest. Therefore, our results implicate that these mutations disrupt the de novo chromatin remodeling activity of the complex without affecting the status of existing nucleosome positioning. J. Cell. Physiol. 226: 1989–1997, 2011. © 2010 Wiley‐Liss, Inc.
In vivo biodistribution of stem cells using molecular nuclear medicine imaging
Authors: Welling Mick M. , Duijvestein Marjolijn , Signore Alberto , van der Weerd Louise
Published: December 2010

Studies on stem cell are rapidly developing since these cells have great therapeutic potential for numerous diseases and has generated much promise as well as confusion due to contradictory results. Major questions in this research field have been raised as to how and in which numbers stem cells home to target tissues after administration, whether the cells engraft and differentiate, and what their long‐term fate is. To answer these questions, reliable in vivo tracking techniques are essential. In vivo molecular imaging techniques using magnetic resonance imaging, bioluminescence, and scintigraphy have been applied for this purpose in experimental studies. The aim of this review is to discuss various radiolabeling techniques for early stem cell tracking, the need for validation of viability and performance of the cells after labeling, and the routes of administration in experimental animal models. In addition, we evaluate current problems and directions related to stem cell tracking using radiolabels, including a possible role for their clinical implementation. J. Cell. Physiol. 226: 1444–1452, 2011. © 2010 Wiley‐Liss, Inc.
Modulation of intracellular glutathione affects adipogenesis in 3T3‐L1 cells
Authors: Vigilanza Paola , Aquilano Katia , Baldelli Sara , Rotilio Giuseppe , Ciriolo Maria Rosa
Published: December 2010

Impairment of redox homeostasis has been extensively associated with obesity, as a consequence of the chronic inflammatory state present in overweight subjects. Deregulation of glutathione (GSH), the most important non‐enzymatic intracellular anti‐oxidant, induces insulin resistance in mature adipocytes, but data are lacking about its effects on adipogenesis. In this report we demonstrate that during adipogenesis of 3T3‐L1 cells the GSH/GSSG ratio decreases, shifting redox status towards oxidizing conditions. Moreover, we demonstrate that inhibition of GSH synthesis, obtained by treatment with L‐buthionine‐sulfoximine (BSO), enhances C/EBPβ LAP/LIP ratio and PPARγ expression during mitotic clonal expansion (MCE) stimulating adipogenesis. On the contrary, GSH ethyl ester (GSHest) supplementation completely abrogates this process also in the presence of BSO. GSH decrement during the first 24 h of adipogenesis is sufficient to induce higher triglyceride accumulation in differentiated adipocytes with respect to control, whereas GSHest treatment inhibits lipid droplets formation. We further demonstrate that Resveratrol (RV) could exert anti‐adipogenic properties also by increasing GSH content through γ‐glutamyl‐cysteine ligase (GCL) induction. Overall data indicate that in pre‐adipocytes the decrease of GSH accelerates adipogenesis, suggesting that the use of agents able to maintain GSH redox status in adipose tissue, such as RV, could be promising in stopping the lipogenic loop of obesity. J. Cell. Physiol. 226: 2016–2024, 2011. © 2010 Wiley‐Liss, Inc.
Association between adherens junctions and tight junctions via rap1 promotes barrier protective effects of oxidized phospholipids
Authors: Birukova Anna A. , Zebda Noureddine , Fu Panfeng , Poroyko Valery , Cokic Ivan , Birukov Konstantin G.
Published: December 2010

Previous studies showed that cyclopenthenone‐containing products resulting from oxidation of a natural phospholipid, 1‐palmitoyl‐2‐arachidonoyl‐sn‐glycero‐3‐phosphorylcholine (OxPAPC) exhibit potent barrier‐protective effects in the in vitro and in vivo models of lung endothelial cell (EC) barrier dysfunction, and these effects are associated with enhancement of peripheral actin cytoskeleton, cell–cell and cell–substrate contacts driven by activation of Rac and Cdc42 GTPases. Rap1 GTPase is another member of small GTPase family involved in control of cell–cell interactions; however, its involvement in EC barrier‐protective effects by OxPAPC remains unknown. This study examined a role of Rap1 in regulation of OxPAPC‐induced interactions in adherens junctions (AJ) and tight junctions (TJ) as a novel mechanism of EC barrier preservation in vitro and in vivo. Immunofluorescence analysis, subcellular fractionation, and co‐immunoprecipitation assays indicate that OxPAPC promoted accumulation of AJ proteins: VE‐cadherin, p120‐catenin, and β‐catenin; and TJ proteins: ZO‐1, occludin, and JAM‐A in the cell membrane, and induced novel cross‐interactions between AJ and TJ protein complexes, that were dependent on OxPAPC‐induced Rap1 activation. Inhibition of Rap1 function suppressed OxPAPC‐mediated pulmonary EC barrier enhancement and AJ and TJ interactions in vitro, as well as inhibited protective effects of OxPAPC against ventilator‐induced lung injury in vivo. These results show for the first time a role of Rap1‐mediated association between adherens junctions and tight junction complexes in the OxPAPC‐induced pulmonary vascular EC barrier protection. J. Cell. Physiol. 226: 2052–2062, 2011. © 2010 Wiley‐Liss, Inc.
Continuous cyclic mechanical tension inhibited Runx2 expression in mesenchymal stem cells through RhoA‐ERK1/2 pathway
Authors: Shi Yu , Li Huiwu , Zhang Xiaoling , Fu Yujie , Huang Yan , Lui Pauline Po Yee , Tang Tingting , Dai Kerong
Published: December 2010

Tensile load is known to regulate the osteogenesis of mesenchymal stem cells (MSCs) and osteogenic progenitors; therefore it is widely used in clinical treatment and tissue engineering. Meanwhile, in vitro, both published studies and our lab data demonstrate that the application of intermittent tensile loading which stimulates cells several minutes or hours each day for several days has promoted the osteogenic differentiation of MSCs. Whereas, for clinic trails, it is important to know accurately how and how long mechanical tension should be applied. Hence, it is necessary to investigate different kinds of mechanical tension on osteogenesis of MSCs. Until now, during the osteogenesis, there has been no research on the effect of continuous cyclic mechanical tension (CCMT) which provides continuous stimulation throughout the study period. We firstly figure out CCMT inhibiting the expression of osteogenic genes such as key transcription factor Runx2. It is known that RhoA regulates cell differentiation in response to mechanical stimuli. MAPK signaling acts as a downstream effector of RhoA. So, we ask in MSCs, if CCMT regulates the osteogenic master gene Runx2 through RhoA‐ERK1/2 pathway. And then, we find out there is a decrease in RhoA activity after CCMT stimulation. Pre‐treatment of CCMT‐loaded MSCs with LPA, a RhoA activator, restores ALP activity and significantly rescues Runx2 expression, while pre‐treatment with C3 toxin, a RhoA inhibitor, further decreases the activity of ALP and down‐regulates the expression of Runx2. Following results indicate that the inhibition of Runx2 expression after CCMT stimulation is mediated by RhoA‐ERK1/2 pathway. J. Cell. Physiol. 226: 2159–2169, 2011. © 2010 Wiley‐Liss, Inc.
TRB3 mediates homocysteine‐induced inhibition of endothelial cell proliferation
Authors: Zou Tong , Liu Wen‐Jing , Li Shu‐De , Zhou Wei , Yang Jie‐Fu , Zou Cheng‐Gang
Published: December 2010

Hyperhomocysteinemia (HHcy) has been shown to induce endothelial dysfunction, an early event in the progression of atherosclerosis. However, the underlying mechanism of endothelial cell injury in HHcy has not been clearly elucidated. In this study, we examined the effect of homocysteine on tribbles‐related protein 3 (TRB3)‐mediated cell‐cycle arrest in human umbilical vein endothelial cells (HUVECs). Treatment of HUVECs with homocysteine (0–250 µmol/L) resulted in inhibition of cell proliferation assessed by [3H]‐thymidine incorporation into DNA. Homocysteine induced cell‐cycle arrest in the G1 phase by up‐regulating the protein levels of p27kip1. Under these conditions, homocysteine did not induce endoplasmic reticulum stress. However, homocysteine up‐regulated the expression of TRB3, thus leading to the dephosphorylation of Akt (Thr308). Knock‐down of endogenous TRB3 using siRNA significantly suppressed the inhibitory effect of homocysteine on the proliferation of HUVECs. Homocysteine‐induced TRB3 expression was mediated by the cAMP/cAMP response element‐binding protein (CREB) pathway. These results demonstrate that TRB3 is a critical molecule in the homocysteine‐mediated cell‐cycle arrest in endothelial cells. J. Cell. Physiol. 226: 2782–2789, 2011. © 2011 Wiley‐Liss, Inc.