bluuebunny/crossref_metadata_2025 huggingface dataset:
Severity of urban transit bus crashes in Bangladesh
Authors: Barua Upal , Tay Richard
Published: March 2010

Unlike in developed countries where buses are a relatively safe mode of transport, there is a significant safety concern in many developing countries like Bangladesh regarding transit buses. Nevertheless, few studies have examined the factors contributing to the number or severity of bus crashes. Using the ordered probit model on bus crash data from 1998 to 2005 in Dhaka, Bangladesh, our study shows that there is a general increase in the severity of transit bus crashes over this period. Also, crash severity tends to increase when the collision occurs on weekends, off‐peak periods, and two‐way streets or involves only one vehicle, a pedestrian, and other vulnerable road users. On the other hand, the severity of a crash tends to be lower at locations with some form of police control or road medians, as well as for crashes involving hit object, parked vehicles, or sideswipes. Copyright © 2010 John Wiley & Sons, Ltd.
Anatomy of Long‐Lasting Love Affairs with Lithium Carbenoids: Past and Present Status and Future Prospects
Authors: Capriati Vito , Florio Saverio
Published: March 2010

After a long adolescence, the chemistry of lithium carbenoids has currently been entering its maturity bringing a dowry of a more in‐depth and less empirical knowledge of the structure and configurational stability of such double‐faced intermediates; this, thanks in particular to the synergistic and harmonic cooperation between calculations and the most modern NMR techniques now at our disposal. Such knowledge has stimulated the development of fruitful stereoselective applications in the field of organic synthesis, providing in addition a rationale to observed selectivities. Such aspects together with the role played by aggregation and solvation on the structure–reactivity relationship are highlighted throughout this Minireview with selected examples extracted from recent literature.
General Method for the 11C‐Labeling of 2‐Arylpropionic Acids and Their Esters: Construction of a PET Tracer Library for a Study of Biological Events Involved in COXs Expression
Authors: Takashima‐Hirano Misato , Shukuri Miho , Takashima Tadayuki , Goto Miki , Wada Yasuhiro , Watanabe Yasuyoshi , Onoe Hirotaka , Doi Hisashi , Suzuki Masaaki
Published: March 2010

Cyclooxygenase (COX) is a critical enzyme in prostaglandin biosynthesis that modulates a wide range of biological functions, such as pain, fever, and so on. To perform in vivo COX imaging by positron emission tomography (PET), we developed a method to incorporate 11C radionuclide into various 2‐arylpropionic acids that have a common methylated structure, particularly among nonsteroidal anti‐inflammatory drugs (NSAIDs). Thus, we developed a novel 11C‐radiolabeling methodology based on rapid C‐[11C]methylation by the reaction of [11C]CH3I with enolate intermediates generated from the corresponding esters under basic conditions. One‐pot hydrolysis of the above [11C]methylation products also allows the synthesis of desired 11C‐incorporated acids. We demonstrated the utility of this method in the syntheses of six PET tracers, [11C]Ibuprofen, [11C]Naproxen, [11C]Flurbiprofen, [11C]Fenoprofen, [11C]Ketoprofen, and [11C]Loxoprofen. Notably, we found that their methyl esters were particularly useful as proradiotracers for a study of neuroinflammation. The microPET studies of rats with lipopolysaccharide (LPS)‐induced brain inflammation clearly showed that the radioactivity of PET tracers accumulated in the inflamed region. Among these PET tracers, the specificity of [11C]Ketoprofen methyl ester was demonstrated by a blocking study. Metabolite analysis in the rat brain revealed that the methyl esters were initially taken up in the brain and then underwent hydrolysis to form pharmacologically active forms of the corresponding acids. Thus, we succeeded in general 11C‐labeling of 2‐arylpropionic acids and their methyl esters as PET tracers of NSAIDs to construct a potentially useful PET tracer library for in vivo imaging of inflammation involved in COXs expression.
Total Synthesis and Configurational Assignment of Chondramide A
Authors: Schmauder Anke , Sibley L. David , Maier Martin E.
Published: March 2010

The first total synthesis of the cyclodepsipeptide chondramide A (2 b) is described. This depsipeptide is composed of four subunits, namelyL‐alanine,N‐Me‐D‐tryptophan, 3‐amino‐2‐methoxy‐propionic acid (β‐tyrosine derivative), and a 7‐hydroxy‐alkenoic acid. While the configuration of the stereogenic centers in the 7‐hydroxy‐alkenoic acid were known, the configuration of the tyrosine derivative required clarification and turned out to be (2S,3R) or (2L,3L), respectively. The synthesis of the 3‐amino‐2‐methoxy‐3‐arylpropanoic ester20 brelied on an asymmetric dihydroxylation yielding diolent‐15 afollowed by a regioselective Mitsunobu substitution leading to 3‐azido‐2‐hydroxypropanoate18 b. We could also show that the ester bond in the seco compound26 bcan be fashioned by a Mitsunobu esterification by using hydroxy ester (7S)‐7and the tripeptide acid25 b. This synthesis should allow for the preparation of various analogues.
3,3′‐diaryl‐BINOL phosphoric acids as enantioselective extractants of benzylic primary amines
Authors: Verkuijl Bastiaan J.V. , de Vries Johannes G. , Feringa Ben L.
Published: March 2010

We report that 3,3′‐diaryl‐BINOL phosphoric acids are effective enantioselective extractants in chiral separation methods based on reactive liquid–liquid extraction. These new extractants are capable of separating racemic benzylic primary amine substrates. The effect of the nature of the substituents at the 3,3′‐positions of the host were examined as well as the structure of the substrate, together with important parameters such as the organic solvent, the pH of the aqueous phase, and the host stoichiometry. Titration of the substrate with the host was monitored by FTIR, NMR, UV–Vis, and CD spectroscopy, which provided insight into the structure of the host–guest complex involved in extraction. Chirality 2011. © 2010 Wiley‐Liss, Inc.
Contaminated normal modeling with application to microarray data analysis
Authors: Dai Hongying , Charnigo Richard
Published: March 2010

A contaminated beta model$(1-\gamma) B(1,1) + \gamma B(\alpha,\beta)$is often used to describe the distribution of$P$‐values arising from a microarray experiment. The authors propose and examine a different approach: namely, using a contaminated normal model$(1-\gamma) N(0,\sigma^2) + \gamma N(\mu,\sigma^2)$to describe the distribution of$Z$statistics or suitably transformed$T$statistics. The authors then address whether a researcher who has$Z$statistics should analyze them using the contaminated normal model or whether the$Z$statistics should be converted to$P$‐values to be analyzed using the contaminated beta model. The authors also provide a decision‐theoretic perspective on the analysis of$Z$statistics.The Canadian Journal of Statistics38: 315–332; 2010 © 2010 Statistical Society of Canada
Divergent cancer pathways for early onset and late onset cutaneous malignant melanoma
Authors: Pérez‐Gomez Beatriz , Aragonés Nuria , Pollan Marina
Published: March 2010

Men and women with trunk melanoma have different age distributions. Age‐specific rates in women suggest a possible role of female hormones in this location.
Intensity‐modulated radiotherapy outcomes for oropharyngeal squamous cell carcinoma patients stratified by p16 status
Authors: Shoushtari Asal , Meeneghan Mathew , Sheng Ke , Moskaluk Christopher A. , Thomas Christopher Y. , Reibel James F. , Levine Paul A. , Jameson Mark J. , Keene Kimberly , Read Paul W.
Published: March 2010

BACKGROUND:

Patients with oropharyngeal squamous cell carcinoma (OPSCC) treated with intensity‐modulated radiotherapy (IMRT) were stratified by p16 status, neck dissection, and chemotherapy to correlate these factors with outcomes.

METHODS:

A total of 112 patients with OPSCC treated with IMRT from 2002 to 2008 were retrospectively analyzed. All patients received RT to 66‐70 Gray. Forty‐five of the tumors were p16 positive (p16+), 27 were p16 negative (p16−), and 41 had unknown p16 status. Sixty‐two patients had postradiation neck dissections. Nine patients with p16− tumors and 28 patients with p16+ tumors received chemotherapy. The distribution of T, N, and stage grouping among the p16+ and p16− patients was not significantly different, and 87.5% patients had stage III/IV disease.

RESULTS:

The median follow‐up was 26.3 months. For patients with p16+ tumors, p16− tumors, and the overall cohort, the actuarial 3‐year locoregional progression‐free survival rate was 97.8%,73.5%, and 90.5% respectively (P = .006) and the disease‐free survival rate was 88.2%, 61.4%, and 81.7%, respectively (P = .004). Patients with p16+ tumors had an 89.5% and 87.5% pathologic complete response (CR) on neck dissection with and without chemotherapy, respectively. In contrast, patients with p16− tumors had a 66.7% and 25.0% pathologic CR on neck dissection with and without chemotherapy, respectively.

CONCLUSIONS:

In this series, p16 status was found to be a significant predictive biomarker and patients with p16+ tumors had much better outcomes than patients with p16− tumors. Further investigation is warranted to determine whether less intense therapy is appropriate for selected patients with p16+ OPSCC, whereas more aggressive strategies are needed to improve outcomes in patients with p16− disease. Cancer 2010. © 2010 American Cancer Society.
A phase 2 study of a fixed combination of uracil and ftorafur and leucovorin given orally in a twice‐daily regimen to treat patients with recurrent metastatic breast cancer
Authors: Hortobagyi Gabriel N. , Young Robyn R. , Karwal Mark , Ibrahim Nuhad K. , Hermann Robert , Murray James L. , Watkins Stanley P. , Gore Ira
Published: March 2010

BACKGROUND:

UFT, a combination of uracil and ftorafur, was developed to combine the cytotoxic effects of 5‐fluorouracil (5‐FU) with convenient oral dosing. Leucovorin is combined with UFT to further potentiate the effect of 5‐FU on tumor cells. Orally administered UFT and leucovorin provide higher peak plasma concentrations of 5‐FU and prolonged therapeutic 5‐FU concentrations compared with continuous infusion of 5‐FU.

METHODS:

Ninety‐four patients with metastatic breast cancer who had been previously treated with anthracyclines and/or taxanes were treated with UFT and leucovorin, given orally, for the first 28 days of a 35‐day cycle. The total daily dose of UFT was 300 mg/m2, which was given in 2 divided doses every 12 hours. The primary endpoint was time to disease progression (TTP). Secondary objectives included overall tumor response rate (OR = complete response [CR] + partial response [PR]) and overall survival (OS).

RESULTS:

Of the 94 patients enrolled, 68 were evaluable for efficacy. Although no CRs were observed, 9 patients achieved PRs, for an OR of 13.2% in the evaluable population. The median TTP for the evaluable population was 10.3 weeks, and the proportion of patients free of disease progression at 6 months was 17%. The median OS was 61.6 weeks for all patients enrolled. The most common drug‐related ≥ grade 3 adverse events (graded using the National Cancer Institute Common Toxicity Criteria version 2) were diarrhea, asthenia, nausea, and dehydration.

CONCLUSIONS:

The combination of UFT and leucovorin administered orally in a twice‐daily regimen was found to have modest activity. Grade 3 toxicities were manageable with appropriate dose adjustments in patients with metastatic breast cancer previously treated with anthracyclines and/or taxanes. Cancer 2010. © 2010 American Cancer Society.
Varying recurrence rates and risk factors associated with different definitions of local recurrence in patients with surgically resected, stage I nonsmall cell lung cancer
Authors: Varlotto John M. , Recht Abram , Flickinger John C. , Medford‐Davis Laura N. , Dyer Anne‐Marie , DeCamp Malcolm M.
Published: March 2010

BACKGROUND:

The objective of this study was to examine the effects of different definitions of local recurrence on the reported patterns of failure and associated risk factors in patients who undergo potentially curative resection for stage I nonsmall cell lung cancer (NSCLC).

METHODS:

The study included 306 consecutive patients who were treated from 2000 to 2005 without radiotherapy. Local recurrence was defined either as “radiation” (r‐LR) (according to previously defined postoperative radiotherapy fields), including the bronchial stump, staple line, ipsilateral hilum, and ipsilateral mediastinum; or as “comprehensive” (c‐LR), including the same sites plus the ipsilateral lung and contralateral mediastinal and hilar lymph nodes. All recurrences that were not classified as “local” were considered to be distal.

RESULTS:

The median follow‐up was 33 months. The proportions of c‐LR and r‐LR at 2 years, 3 years, and 5 years were 14%, 21%, and 29%, respectively, and 7%, 12%, and 16%, respectively. Significant risk factors for c‐LR on multivariate analysis were diabetes, lymphatic vascular invasion, and tumor size; and significant factors for r‐LR were resection of less than a lobe and lymphatic vascular invasion. The proportions of distant (nonlocal) recurrence using these definitions at 2 years, 3 years, and 5 years were 10%, 12%, and 18%, respectively, and 14%, 19%, and 29%, respectively. Significant risk factors for distant failure were histology when using the c‐LR definition and tumor size when using the r‐LR definition.

CONCLUSIONS:

Local recurrence increased nearly 2‐fold when a broad definition was used instead of a narrow definition. The definition also affected which factors were associated significantly with both local and distant failure on multivariate analysis. Comparable definitions must be used when analyzing different series. Cancer 2010. © 2010 American Cancer Society.
A finite‐volume method for solids with a rotational degrees of freedom based on the 6‐node triangle
Authors: Pan Wenke , Wheel Marcus
Published: March 2010

A novel vertex‐centred finite‐volume (FV) method is presented for determining the displacement field in loaded 2D structures. The solid is discretized into 6‐node finite elements (FE) and the standard 6‐node FE shape function is employed to describe the displacement variation in each element. However, the displacements of the midside nodes are replaced with the displacements and the rotations of the two neighbouring edge nodes. Thus, only the control volumes centred around each vertex node of the triangular element are required. These control volumes are constructed by joining lines between the centre of the element and the midside nodes. The force equilibrium in two perpendicular directions and one in‐plane moment equilibrium equation is derived for each control volume. By solving the system of equations, the displacements and the rotations of the vertex nodes can be obtained and then the displacements of the midside nodes can be calculated. Following this, the strain and the stress can be determined through the relationship between strain and displacement, and stress and strain, respectively. The results of simulation show that this novel FV method is not only better than the previously derived 3‐node triangle FV method with rotational degrees of freedom, but also better than the 3‐node FE method with rotations, and can also compete with the 6‐node triangle FE method. In addition, no locking problem was encountered as the value of Poisson's ratio of the elastic material approached 0.5. Copyright © 2010 John Wiley & Sons, Ltd.
Surgical correction of scoliosis: Numerical analysis and optimization of the procedure
Authors: Aguilar Madeira J. F. , Pina H. L. , Pires E. B. , Monteiro J.
Published: March 2010

A previously developed model is used to numerically simulate real clinical cases of the surgical correction of scoliosis. This model consists of one‐dimensional finite elements with spatial deformation in which (i) the column is represented by its axis; (ii) the vertebrae are assumed to be rigid; and (iii) the deformability of the column is concentrated in springs that connect the successive rigid elements. The metallic rods used for the surgical correction are modeled by beam elements with linear elastic behavior. To obtain the forces at the connections between the metallic rods and the vertebrae geometrically, non‐linear finite element analyses are performed. The tightening sequence determines the magnitude of the forces applied to the patient column, and it is desirable to keep those forces as small as possible. In this study, a Genetic Algorithm optimization is applied to this model in order to determine the sequence that minimizes the corrective forces applied during the surgery. This amounts to find the optimal permutation of integers 1, …,n,nbeing the number of vertebrae involved. As such, we are faced with a combinatorial optimization problem isomorph to the Traveling Salesman Problem. The fitness evaluation requires one computing intensive Finite Element Analysis per candidate solution and, thus, a parallel implementation of the Genetic Algorithm is developed. Copyright © 2010 John Wiley & Sons, Ltd.
A numerical model of neonatal pulmonary atresia with intact ventricular septum and RV‐dependent coronary flow
Authors: Mynard J. P. , Davidson M. R. , Penny D. J. , Smolich J. J.
Published: March 2010

We developed a numerical model of the neonatal arterial and coronary circulations in the context of pulmonary atresia with intact ventricular septum (PAIVS). PAIVS is a congenital heart defect characterized by a blocked pulmonary valve orifice and elevated right ventricular (RV) pressure, and is often associated with an abnormal connection (fistula) between the RV cavity and a coronary artery (e.g. the left anterior descending artery, LAD). A proximal coronary stenosis is also common and can result in RV‐dependent coronary flow, where decompression of the RV by surgical repair of the atresia leads to compromised coronary flow (ischaemia). Using a combined one‐dimensional and lumped parameter model, we simulated PAIVS to investigate the effects of an RV‐LAD fistula, LAD stenosis and RV decompression on coronary haemodynamics. We also simulated coronary collaterals, which develop in response to inadequate blood flow, and found that these may provide little protection against ischaemia in the setting of PAIVS with RV‐LAD fistula and LAD stenosis if collateral flow is preferentially directed to the low‐resistance fistula. While the focus of this study was PAIVS, the techniques presented may be applied to a variety of complex congenital heart defects that include abnormal vascular connections and unusual coronary anatomy. Copyright © 2010 John Wiley & Sons, Ltd.
A linguistic interpretation of Welford's hijack hypothesis
Authors: Brown Mark
Published: March 2010

This paper makes a linguistic reinterpretation of Welford's 1997 hijack hypothesis, arguing that the hijack of the discourse of the radical environment is simply a process of appropriation, i.e., the adoption of particular words in order to make use of them within the green corporations' own frames of experience. Results are presented from an empirical study using two large ‘databases’ of language. These are electronic collections of texts taken from British environmental organizations – the radical non‐governmental organizations (NGOs), and UK corporations that wish to be environmentally friendly – green business. The results show that there are very marked differences in the physical contextualization of a selection of words which are used by both the radical NGOs and green business. The paper concludes by noting the need to take the analysis a stage further by comparing the usage of particular words by the two discourse communities. Copyright © 2010 John Wiley & Sons, Ltd and ERP Environment.
A reinterpretation of the principles of CSR: a pragmatic approach
Authors: Blindheim* Bjørn‐Tore , Langhelle Oluf
Published: March 2010

Theories of Corporate Social Performance (CSP) have been criticized for lacking a clear normative theory of business in society capable of prescribing how management practice can reasonable move from ‘what is’ to ‘what should be’. This paper argues for a pragmatic approach to the role and responsibility of business in society in which the normative deficiencies of CPS theory can be strengthened through democratic iterations over some or the other ethical treatise, and thus come to constitute a justified foundation for companies' efforts in the societal arena. We illustrate our approach to a normative theory of business in society by reinterpreting the principles of corporate social responsibility (CSR) – constituting the normative foundation of CSP theory – from the vantage point of sustainable development. Copyright © 2010 John Wiley & Sons, Ltd and ERP Environment.
Culture and sustainability
Authors: Packalén Sture
Published: March 2010

Sustainability is only attainable if we regard it as a culture‐transforming, creative project for the entire society. It is therefore important to discuss the potential of art and culture for shaping a desirable future. A vital culture and sustainable development go hand in hand. Sustainability can be seen as a constant, ongoing process of searching and self‐reflection about our present and our future. The search must consist of a constant review of social norms, values, and practical approaches. The search and reflection need culture as a medium to give shape to the communication that is necessary in order for sustainable development to come about in the economic, ecological and social spheres. Copyright © 2010 John Wiley & Sons, Ltd and ERP Environment.
Heterokaryotic nuclear conditions and a heterogeneous nuclear population are observed by flow cytometry in Phytophthora infestans
Authors: Catal Mursel , King Louis , Tumbalam Pavani , Wiriyajitsomboon Prissana , Kirk William W. , Adams Gerard C.
Published: March 2010

A simple and reliable method for preparation of whole nuclei of a common oomycete, Phytophthora infestans, is described for laser flow cytometry. The ease of preparation, the absence of detectable debris and aggregates, and the precision in determinations of DNA content per nucleus improve interpretation and understanding of the genetics of the organism. Phytophthora infestans is the pathogen that causes potato and tomato late blight. The genetic flexibility of P. infestans and other oomycete pathogens has complicated understanding of the mechanisms of variation contributing to shifts in race structure and virulence profiles on important agricultural crops. Significant phenotypic and genotypic changes are being reported in the apparent absence of sexual recombination in the field. Laser flow cytometry with propidium iodide is useful in investigating the nuclear condition of the somatic colony of field strains of P. infestans. The majority of the studied strains contain a single population of nuclei in nonreplicated diplophase. However, mean DNA content per nucleus varies considerably among isolates confirming the heterogeneity of the nuclear population in regard to C‐value, for field isolates. Nuclear DNA content varies from 1.75× to 0.75× that of nuclei in a standard strain from central Mexico. Some strains contain two to three populations of nuclei with differing DNA contents in the mycelium and are heterokaryons. Such a range in DNA content suggests DNA‐aneuploidy, but direct confirmation of aneuploidy will require microscopy of chromosomes. Heterokaryosis and populations of nuclei of differing DNA content necessarily confound standardized assays used worldwide in crop breeding programs for determination of race profiles and virulence phenotypes of this important pathogen. © 2010 International Society for Advancement of Cytometry
Flow cytometric profiles, biomolecular and morphological aspects of transfixed leukocytes and red cells
Authors: Canonico Barbara , Betti Michele , Luchetti Francesca , Battistelli Michela , Falcieri Elisabetta , Ferri Paola , Zamai Loris , Barnett David , Papa Stefano
Published: March 2010

Background:

We evaluated the effects of the TransFixTM short‐term stabilization technique on leukocyte subpopulations in both optimal and adverse storage temperatures and on different cellular concentrations. Particularly, we analyzed DNA cell content and membrane structure also for erythrocytes using a multiparametric approach.

Methods:

We studied biomolecular and morphological aspects of transfixed cells, by means of SEM, TEM, Western blotting, and by flow cytometry (FC). Furthermore, FC, Tunel, and electrophoresis were applied to evaluate DNA behavior.

Results:

We confirm preservation of scatter characteristics and immunophenotyping, extending such evaluations to cells stored in suboptimal conditions (25°C and 37°C) and in high density. Data demonstrate for lymphomonocytic cells an optimal conservation, slightly decreasing at higher temperatures for both 1/5 and 1/10 ratio (TransFix™/sample), with enhanced autofluorescence. Eosinophils, basophils, and neutrophils are shown to preserve differently over time. The three different cellular concentrations evaluated (30,000–120,000 cell/μl) demonstrate substantial stability in FI values. Furthermore DNA content analysis attests the absence of any apoptotic pattern. Transfixed red cell protein profile as well as their morphological features appears almost unaltered.

Conclusions:

Cytometric performance is suboptimal in aged unfixed specimens because of apoptosis that affects light scatter properties. Our findings highlight that lymphomonocytic cells are well stabilized even at suboptimal temperature and cell density. TransFix™ is able to abolish any apoptotic features and acts as an optimal blood preservative for appropriate preanalytical stabilization. © 2010 Clinical Cytometry Society
The storm and stress of adolescence: Insights from human imaging and mouse genetics
Authors: Casey B.J. , Jones Rebecca M. , Levita Liat , Libby Victoria , Pattwell Siobhan S. , Ruberry Erika J. , Soliman Fatima , Somerville Leah H.
Published: March 2010

The characterization of adolescence as a time of “storm and stress” remains an open debate. Intense and frequent negative affect during this period has been hypothesized to explain the increased rates of affective disorders, suicide, and accidental death during this time of life. Yet some teens emerge from adolescence with minimal turmoil. We provide a neurobiological model of adolescence that proposes an imbalance in the development of subcortical limbic (e.g., amygdala) relative to prefrontal cortical regions as a potential mechanism for heightened emotionality during this period. Empirical support for this model is provided from recent behavioral and human imaging studies on the development of emotion regulation. We then provide examples of environmental factors that may exacerbate imbalances in amygdala‐ventrofrontal function increasing risk for anxiety related behaviors. Finally we present data from human and mouse studies to illustrate how genetic factors may enhance or diminish this risk. Together, these studies provide a converging methods approach for understanding the highly variable stress and turmoil experienced in adolescence. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 225–235, 2010
Proinsulin C‐peptide prevents type‐1 diabetes‐induced decrease of renal Na+‐K+‐ATPase α1‐subunit in rats
Authors: Nordquist Lina , Shimada Kohei , Ishii Tatsuya , Furuya Daniela Tomie , Kamikawa Akihiro , Kimura Kazuhiro
Published: March 2010

Aims/Hypothesis

C‐peptide reduces renal damage in diabetic patients and experimental animal models. In vitro studies suggest that the renal effects of C‐peptide may, in part, be explained by stimulation of Na+/K+‐ATPase activity. However, the responses of Na+/K+‐ATPase expression in the kidney of diabetic animals to C‐peptide administration remain unclear. The aim of this study was to clarify the responses.

Methods

Type 1 diabetic rats were produced by injecting streptozotocin (STZ), and some of the rats were treated with either C‐peptide or insulin by the aid of an osmotic pump for 1 week. The mRNA expression and immunohistochemical localization of Na+/K+‐ATPase α1‐, α2‐ and β3‐subunits were investigated in the kidney of these rats.

Results

Na+/K+‐ATPase α1‐subunit was abundantly expressed in the medullary collecting ducts of control animals, but the expression was markedly decreased in the diabetic state with concomitant decrease in its mRNA expression. Similar decreases were observed in the insulin‐treated diabetic rats, whereas in the C‐peptide‐treated diabetic rats, there was no reduction in the α1‐expression. The β3‐subunit was expressed in podocytes and parietal cells in the glomeruli, vascular endothelial cells, and cortical collecting ducts, but lesser signals were observed in the proximal and distal tubules. However, the β3‐subunit did not appear to be affected by the diabetic state.

Conclusions

Diabetes selectively reduced Na+/K+‐ATPase α1‐subunit expression and abundance. Chronic administration of C‐peptide prevented this decrease. This implies a role for C‐peptide in the long‐term regulation of Na+/K+‐ATPase function. Copyright © 2010 John Wiley & Sons, Ltd.
Analysis of Free and Total Glycerol in Biodiesel Using an Electrochemical Assay Based on a Two‐Enzyme Oxygen‐Electrode System
Authors: Luetkmeyer Tacia , dos Santos Rosana Monteiro , da Silva Adriana Barbosa , Amado Roberto Salgado , de Castro Vieira Eduardo , D'Elia Eliane
Published: March 2010

In this work, an electroenzymatic methodology based on two coupled enzymatic activities (glycerokinase and glycerol‐3‐phosphate oxidase) was developed using an oxygen Clark‐type electrode for the determination of free and total glycerol in biodiesel samples. The enzymatic conversion of glycerol consumes oxygen, which is measured amperometrically in a Clark‐type electrode and correlated with the concentration of glycerol in the sample. The electroenzymatic method proposed showed a good linear correlation coefficient (R=0.9990) with a linear response in the concentration range of 6.25×10−5 to 6.25×10−4% (w/v) and limits of detection and quantification at 1.0×10−5% and 3.0×10−5% (w/v), respectively. Good correlations were found between the results obtained in this work and those by the gas chromatography technique (R=0.9994). The proposed method was shown to be promising for the analysis of glycerol in biodiesel samples, with a simple and inexpensive methodology compared with the gas chromatography technique.
Methylated Azopyridine as a New Electron Transfer Mediator for the Electrocatalytic Oxidation of NADH
Authors: Safavi Afsaneh , Moradlou Omran , Saadatifar Mostafa
Published: March 2010

Carbon ionic liquid electrode (CILE) has been modified with a new synthesized mediator i.e. N,N′‐dimethyl‐4,4′‐azopyridinium hexafluorophosphate (MAZPHP) via sol process and the electron transfer mediating characteristics of this mediator has been evaluated. 4,4′‐Azopyridine (AZP) did not show any electrocatalytic activity toward the selected probe, NADH, while its synthesized methylated derivative, MAZPHP, is a very efficient mediator for the electrocatalytic NADH oxidation. Cyclic voltammetry of MAZPHP/Sol/CILE exhibited a pair of reversible peaks corresponding to incorporated mediator with a formal potential of about 221 mV vs. Ag/AgCl. MAZPHP/Sol/CILE is free from fouling effects by the oxidation products of NADH which generally give hindrance to amperometric detection of NADH. Using amperometric technique, NADH can be determined in the range of 1.0×10−5 M to 1.4×10−3 M with a detection limit of 2.0×10−6 M.
Electrocatalytic Reduction and Determination of Iodate and Periodate at Silicomolybdate‐Incorporated‐Glutaraldehyde‐ Cross‐Linked Poly‐L‐lysine Film Electrodes
Authors: Pan Yu‐Ching , Thangamuthu R. , Chen Shen‐Ming
Published: March 2010

The present work describes reduction of iodate (IO3−), and periodate (IO4−) at silicomolybdate‐doped‐glutaraldehyde‐cross‐linked poly‐L‐lysine (PLL‐GA‐SiMo) film coated glassy carbon electrode in 0.1 M H2SO4. In our previous study, we were able to prepare the PLL‐GA‐SiMo film modified electrode by means of electrostatically trapping SiMo12O404− mediator in the cationic film of PLL‐GA, and the voltammetric investigation in pure supporting indicated that the charge transport through the film was fast. Here, the electrocatalytic activity of PLL‐GA‐SiMo film electrode towards iodate and periodate was tested and subsequently used for analytical determination of these analytes by amperometry. The two electron reduced species of SiMo12O404− anion was responsible for the electrocatalytic reduction of IO3− at PLL‐GA‐SiMo film electrode while two and six electron reduced species were showed electrocatalytic activity towards IO4− reduction. Under optimized experimental conditions of amperometry, the linear concentration range and sensitivity are 2.5×10−6 to 1.1×10−2 M and 18.47 μA mM−1 for iodate, and 5×10−6 to 1.43×10−4 M and 1014.7 μA mM−1 for periodate, respectively.
Electrochemical Oxidation of Epinephrine and Uric Acid at a Layered Double Hydroxide Film Modified Glassy Carbon Electrode and Its Application
Authors: Ni Fang , Wang Yinling , Zhang Dandan , Gao Feng , Li Maoguo
Published: March 2010

Increasing attention has been paid to layered double hydroxide (LDH) film modified electrode attributing to its desirable properties for fabrication of electrochemical sensor. In this paper, the Zn‐Al LDH film modified glassy carbon electrode was characterized by electrochemical methods. The enhanced electrocatalytic currents and well‐separated potentials for epinephrine (EP) and uric acid (UA) were observed at the as‐prepared electrode. Under selected condition, the differential pulse voltammetry response of the modified electrode to EP (or UA) shows a linear concentration range of 0.5 μM to 0.3 mM (or 2 μM to 0.4 mM) in the presence of 10.0 μM UA (or 20.0 μM EP). At a signal‐to‐noise ratio of 3, the calculated limits of detection are 0.13 μM and 0.66 μM, respectively. The proposed method has been performed to successfully detect EP and UA in analysis of real samples, such as in EP injection solution and human urine samples.
Determination of Fe2+ and Fe3+ in Aqueous Solutions Containing Food Chelators by Differential Pulse Anodic Stripping Voltammetry
Authors: Scheers Nathalie , Andlid Thomas , Alminger Marie , Sandberg Ann‐Sofie
Published: March 2010

The objective was to investigate interactions between iron and food chelators in an aqueous environment. The net complexation were investigated by DPASV in a NaClO4 electrolyte using a platinum electrode. The experimental conditions were simulating the environment of the human duodenum. The results indicated a net coordination affinity between Fe2+ and the organic acids in the following order; ascorbic acid≈phytate>pyruvate>lactate>acetate. For Fe3+ net complexation, the stability was in the order of lactate>phytate>pyruvate>acetate>citrate. In conclusion, DPASV in conjunction with a platinum electrode is suitable for studies in aqueous systems where the net complexation of metal is important.
Epigenetic alterations of the SERPINE1 gene in oral squamous cell carcinomas and normal oral mucosa
Authors: Gao Shan , Nielsen Boye Schnack , Krogdahl Annelise , Sørensen Jens Ahm , Tagesen Jan , Dabelsteen Sally , Dabelsteen Erik , Andreasen Peter A.
Published: March 2010

A high level of plasminogen activator inhibitor‐1 (PAI‐1 or SERPINE1) in tumor extracts is a marker of a poor prognosis in human cancers, including oral carcinomas. However, the mechanisms responsible for the upregulation of PAI‐1 in cancers remain unclear. Investigating specific PAI‐1 expressing cells in oral carcinomas by immunohistochemistry, we found that PAI‐1 was expressed in 18 of the 20 patients, mainly by cancer cells. Two showed PAI‐1 positive stromal cells surrounding the tumor areas and five showed PAI‐1 positive cells in tumor‐adjacent normal epithelium. By real‐time RT‐PCR analysis, 17 of 20 patients with oral carcinoma were found to have between 2.5‐ and 50‐fold increased tumor PAI‐1 mRNA level, as compared with the matched tumor‐adjacent normal tissues. The PAI‐1 mRNA level in connective tissues from 15 healthy volunteers was similar to the level in tumor‐adjacent normal tissues, but the level in epithelium was 5‐ to 10‐fold lower. Analyzing DNA methylation of 25 CpG sites within 960 bp around the transcription initiation site of the SERPINE1 gene by bisulfite sequencing, we did the surprising observation that both tumors and tumor‐adjacent normal tissue had a significant level of methylation, whereas there was very little methylation in tissue from healthy volunteers, suggesting that tumor‐adjacent normal tissue already contains transformation‐associated epigenetic changes. However, there was no general inverse correlation between PAI‐1 mRNA levels and SERPINE1 gene methylation in all tissues, showing that CpG methylation is not the main determinant of the PAI‐1 expression level in oral tissue. © 2010 Wiley‐Liss, Inc.
Comprehensive genetic analysis of seven large families with mismatch repair proficient colorectal cancer
Authors: Middeldorp Anneke , Jagmohan‐Changur Shantie C. , van der Klift Heleen M. , van Puijenbroek Marjo , Houwing‐Duistermaat Jeanine J. , Webb Emily , Houlston Richard , Tops Carli , Vasen Hans F. A. , Devilee Peter , Morreau Hans , van Wezel Tom , Wijnen Juul
Published: March 2010

Approximately 40% of colorectal cancer (CRC) families with a diagnosis of hereditary nonpolyposis CRC on the basis of clinical criteria are not a consequence of mismatch repair (MMR) deficiency. Such families provide supporting evidence for the existence of a hitherto unidentified highly penetrant gene mutation. To gain further understanding of MMR‐competent familial colorectal cancer (FCC), we studied seven large families with an unexplained predisposition for CRC to identify genetic regions that could harbor CRC risk factors. First, we conducted a genome‐wide linkage scan using 10K single‐nucleotide polymorphism (SNP) arrays to search for disease loci. Second, we studied the genomic profiles of the tumors of affected family members to identify commonly altered genomic regions likely to harbor tumor suppressor genes. Finally, we studied the possible role of recently identified low‐risk variants in the familial aggregation of CRC in these families. Linkage analysis did not reveal clear regions of linkage to CRC. However, our results provide support linkage to 3q, a region that has previously been linked to CRC susceptibility. Tumor profiling did not reveal any genomic regions commonly targeted in the tumors studied here. Overall, the genomic profiles of the tumors show some resemblance to sporadic CRC, but additional aberrations were also present. Furthermore, the FCC families did not appear to have an enrichment of low‐risk CRC susceptibility loci. These data suggest that factors other than a highly penetrant risk factor, such as low or moderate‐penetrance risk factors, may explain the increased cancer risk in a subset of familial CRCs. © 2010 Wiley‐Liss, Inc.
Predicting and memorizing observed action: Differential premotor cortex involvement
Authors: Stadler Waltraud , Schubotz Ricarda I. , von Cramon D. Yves , Springer Anne , Graf Markus , Prinz Wolfgang
Published: March 2010

Many studies have shown the involvement of the premotor cortex in action observation, recognizing this region as the neural marker of action simulation (i.e., internal modeling on the basis of the observer's own motor repertoire). So far, however, we have remained unaware of how action simulation differs from more general action representation in terms of premotor activation. The present fMRI experiment is the first to demonstrate how premotor structures contribute to action simulation as opposed to other action‐related cognitive tasks, such as maintaining action representations. Using similar stimuli, a prediction condition requiring internal simulation of transiently occluded actions was compared to three different action‐related control tasks differing solely in task instructions. Results showed right pre‐SMA activation as a correlate of maintaining action representations in general. Moreover, the prediction condition was most efficient in activating the left pre‐SMA and left PMd. These results suggest that the conjoint activation of the pre‐SMA and PMd reflects a core neural driver of action simulation. Hum Brain Mapp, 2011. © 2010 Wiley‐Liss, Inc.
Differential effects between cyclooxygenase‐2 inhibitors and siRNA on vascular endothelial growth factor production in head and neck squamous cell carcinoma cell lines
Authors: Park Seok‐Woo , Kim Hyo‐Sun , Hah Jeong‐Hun , Kim Kwang‐Hyun , Heo Dae‐Seog , Sung Myung‐Whun
Published: March 2010

Background:

Several researchers have observed that cyclooxygenase‐2 (COX‐2) inhibitors display anticancer effects only at higher concentrations than doses that block COX‐2 activity in head and neck squamous cell carcinoma (HNSCC) cells.

Methods:

To better understand the exact anticancer mechanism of COX‐2‐inhibitors, we compared the effects of pharmacologic inhibitors to those of small‐interfering RNA against COX‐2 on cell‐growth, vascular endothelial growth factor (VEGF) production, and intracellular signaling in HNSCC cell lines.

Results:

We observed in HNSCC cells, that COX‐2‐siRNA induced an inhibitory effect on intracellular signaling, but unlike the pharmacologic inhibitors, did not affect cell proliferation. Whereas the chemical inhibitors increased VEGF synthesis even at low doses, COX‐2‐siRNA showed differential inhibition of VEGF production according to expression patterns of COX‐1 and COX‐2 in tested cells.

Conclusion:

The majority of the anticancer effects of COX‐2‐inhibitors in HNSCC cells seem to result from COX‐2‐independent action, suggesting that COX‐1 and COX‐2 may contribute to VEGF synthesis in cancer cells through a prostaglandin‐dependent mechanism. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Head and neck cancer: Response to p53‐based therapeutics
Authors: Nemunaitis Jackie , Nemunaitis John
Published: March 2010

Limited options are available for patients with advanced stage head and neck cancer. The p53 gene is known as the “guardian of the genome.” Mutations of the p53 gene predispose to carcinogenesis. The p53 mutations are common in head and neck cancer. Replacement of p53 gene function in preclinical models demonstrates cancer regression and improved survival. Clinical data with an adenoviral based p53 gene delivery product (Advexin) supports safety and clinical response after direct intratumoral injection. We summarize p53‐related therapeutics in this review. © 2010 Wiley Periodicals, Inc. Head Neck, 2011
Pharmacodynamic evaluation of temsirolimus in patients with newly diagnosed advanced‐stage head and neck squamous cell carcinoma
Authors: Ekshyyan Oleksandr , Mills Glenn M. , Lian Timothy , Amirghahari Nazanin , Rong Xiaohua , Lowery‐Nordberg Mary , Abreo Fleurette , Veillon Diana M. , Caldito Gloria , Speicher Lisa , Glass Jonathan , Nathan Cherie‐Ann O.
Published: March 2010

Background:

Activation of the mammalian target of rapamycin (mTOR) pathway in surgical margins of head and neck squamous cell carcinoma (HNSCC) is a predictor of recurrence and patients with minimal residual disease may benefit from adjuvant therapy with temsirolimus, an mTOR inhibitor.

Methods:

The effects of 3 weekly doses of 25 mg of temsirolimus on Akt/mTOR pathway biomarkers were evaluated in tumor and peripheral blood mononuclear cells (PBMCs) of patients with HNSCC. Adverse events were assessed.

Results:

Temsirolimus significantly decreased pS6 and p4E‐BP1 in tumors, and pS6 and pAkt in PBMCs (p < .05). There was no significant upregulation of pAkt(Ser473) in tumor tissue. Side effects were minimal and reversible.

Conclusion:

Significant inhibition of the mTOR pathway was noted in both tumors and PBMCs of HNSCC with minimal side effects. The mTOR inhibitors can potentially be used as adjuvant therapy for patients with minimal residual disease and PBMCs are potential surrogate markers in this setting. © 2010 Wiley Periodicals, Inc. Head Neck, 2010
Three New Diterpenoids from Rabdosia lophanthoides var. gerardiana
Authors: Li Chen‐Yang , Gao Hao , Jiao Wei‐Hua , Zhang Long , Zhou Guang‐Xiong , Yao Xin‐Sheng
Published: March 2010

Three new diterpenoids, together with three known ones, were isolated from the air‐dried whole herbs of Rabdosia lophanthoides var. gerardiana. The structures of the new diterpenoids were established as 3,4‐dihydro‐11‐hydroxy‐10‐(1‐hydroxy‐1‐methylethyl)‐2,2,6‐trimethylnaphtho[1,8‐bc]oxocin‐5(2H)‐one (1), 11,12,15‐trihydroxyabieta‐5,8,11,13‐tetraen‐7‐one (2), (2R,3S,4S,4aR,8S,9aS,13aS,16aS)‐3,4,4a,8,9,9a,10,11,12,13,14,16a‐dodecahydro‐2‐(hydroxymethyl)‐6,6,10,10‐tetramethyl‐2H‐benzo[4,5]cyclohepta[1,2‐h]pyrano[2,3‐b][1,4]benzodioxepine‐3,4,8,13a,15(6H)‐pentol (3) by spectroscopic methods, including extensive 1D‐ and 2D‐NMR analyses. The structures of the known compounds were identified by comparison of their physical and spectroscopic data with those reported in the literature.
Synthesis of Novel Spiropyrimidinones
Authors: Amutha Parasuraman , Nagarajan Samuthirapandian
Published: March 2010

An efficient one‐pot synthesis of new spirocyclic 2‐aminopyrimidinones via the three‐component reaction of a cyclic ketone, alkyl cyanoacetate, and guanidinium carbonate was developed via a domino reaction.
One‐Pot, Three‐Component Synthesis of 1‐(2‐Hydroxyethyl)‐1H‐1,2,3‐triazole Derivatives by Copper‐Catalyzed 1,3‐Dipolar Cycloaddition of 2‐Azido Alcohols and Terminal Alkynes under Mild Conditions in Water
Authors: Sharghi Hashem , Hosseini‐Sarvari Mona , Moeini Fatemeh , Khalifeh Reza , Beni Alireza Salimi
Published: March 2010

A safe, efficient, and improved procedure for the regioselective synthesis of 1‐(2‐hydroxyethyl)‐1H‐1,2,3‐triazole derivatives under ambient conditions is described. Terminal alkynes reacted with oxiranes and NaN3 in the presence of a copper(I) catalyst, which is prepared by in situ reduction of the copper(II) complex 4 with ascorbic acid, in H2O. The regioselective reactions exclusively gave the corresponding 1,4‐disubstituted 1H‐1,2,3‐triazoles in good to excellent yields. This procedure avoids the handling of organic azides as they are generated in situ, making this already powerful click process even more user‐friendly and safe. The remarkable features of this protocol are high yields, very short reaction times, a cleaner reaction profile in an environmentally benign solvent (H2O), its straightforwardness, and the use of nontoxic catalysts. Furthermore, the catalyst could be recovered and recycled by simple filtration of the reaction mixture and reused for ten consecutive trials without significant loss of catalytic activity. No metal‐complex leaching was observed after the consecutive catalytic reactions.