bluuebunny/crossref_metadata_2025 huggingface dataset:
Lanthanide amides [(Me3Si)2N]3Ln(µ‐Cl)Li(THF)3‐catalyzed phospho‐aldol‐brook rearrangement reaction of dialkyl phosphites with isatins
Authors: Wang Lu , Yao Zhigang , Xu Fan , Shen Qi
Published: August 2012

The tetracoordinated lanthanide amides [(Me3Si)2N]3Ln(µ‐Cl)Li(THF)3 were found to serve as highly active catalysts for the phospho‐Aldol‐Brook rearrangement reaction of various dialkyl phosphites and isatins. The reactions produced dialkyl 2‐oxoindolin‐3‐yl phosphates in good to excellent yields in the presence of 1 mol% [(Me3Si)2N]3La(µ‐Cl)Li(THF)3 at room temperature within 5 min. A mechanism for this highly efficient process was proposed. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:449–456, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.21036
Palladium(II) complexes with aminomethylphosphine ligands as catalysts for the heck reaction
Authors: Keleş Mustafa , Yılmaz Mustafa Kemal
Published: August 2012

New, aminomethyldiphosphine (PCN) ligands, ((C6H5)2PCH2)2NR (R = C6H3 (CH3)(OH) (1a), C6H4OC6H5(1b), C6H4SC6H5) (1c)) and their Pd(II) complexes have been synthesized and characterized. These complexes were found to be efficient catalysts in the Heck reaction of activated and deactivated aryl halide with a variety of olefins. © 2012 Wiley Periodicals, Inc. Heteroatom Chem 23:466–471, 2012; View this article online at wileyonlinelibrary.com. DOI 10.1002/hc.21038
Intravenous N-acetylcysteine in pediatric patients with nonacetaminophen acute liver failure: A placebo-controlled clinical trial
Authors: Squires Robert H. , Dhawan Anil , Alonso Estella , Narkewicz Michael R. , Shneider Benjamin L. , Rodriguez-Baez Norberto , Olio Dominic Dell , Karpen Saul , Bucuvalas John , Lobritto Steven , Rand Elizabeth , Rosenthal Philip , Horslen Simon , Ng Vicky , Subbarao Girish , Kerkar Nanda , Rudnick David , Lopez James M. , Schwarz Kathleen , Romero Rene , Elisofon Scott , Doo Edward , Robuck Patricia R. , Lawlor Sharon , Belle Steven H.
Published: August 2012

N-acetylcysteine (NAC) was found to improve transplantation-free survival in only those adults with nonacetaminophen (non-APAP) acute liver failure (ALF) and grade 1-2 hepatic encephalopathy (HE). Because non-APAP ALF differs significantly between children and adults, the Pediatric Acute Liver Failure (PALF) Study Group evaluated NAC in non-APAP PALF. Children from birth through age 17 years with non-APAP ALF enrolled in the PALF registry were eligible to enter an adaptively allocated, doubly masked, placebo-controlled trial using a continuous intravenous infusion of NAC (150 mg/kg/day in 5% dextrose in water [D5W]) or placebo (D5W) for up to 7 days. The primary outcome was 1-year survival. Secondary outcomes included liver transplantation-free survival, liver transplantation (LTx), length of intensive care unit (ICU) and hospital stays, organ system failure, and maximum HE score. A total of 184 participants were enrolled in the trial with 92 in each arm. The 1-year survival did not differ significantly (

P

= 0.19) between the NAC (73%) and placebo (82%) treatment groups. The 1-year LTx-free survival was significantly lower (

P

= 0.03) in those who received NAC (35%) than those who received placebo (53%), particularly, but not significantly so, among those less than 2 years old with HE grade 0-1 (NAC 25%; placebo 60%;

P

= 0.0493). There were no significant differences between treatment arms for hospital or ICU length of stay, organ systems failing, or highest recorded grade of HE.

Conclusion

: NAC did not improve 1-year survival in non-APAP PALF. One-year LTx-free survival was significantly lower with NAC, particularly among those <2 years old. These results do not support broad use of NAC in non-APAP PALF and emphasizes the importance of conducting controlled pediatric drug trials, regardless of results in adults.
Accumulated state assessment of the Peace-Athabasca-Slave River system
Authors: Dubé Monique G , Wilson Julie E
Published: August 2012

Effects-based analysis is a fundamental component of watershed cumulative effects assessment. This study conducted an effects-based analysis for the Peace-Athabasca-Slave River System, part of the massive Mackenzie River Basin, encompassing 20% of Canada's total land mass and influenced by cumulative contributions of the W.A.C. Bennett Dam (Peace River) and industrial activities including oil sands mining (Athabasca River). This study assessed seasonal changes in 1) Peace River water quality and quantity before and after dam development, 2) Athabasca River water quality and quantity before and after oil sands developments, 3) tributary inputs from the Peace and Athabasca Rivers to the Slave River, and 4) upstream to downstream differences in water quality in the Slave River. In addition, seasonal benchmarks were calculated for each river based on pre-perturbation post-perturbation data for future cumulative effects assessments. Winter discharge (January–March) from the Peace and Slave Rivers was significantly higher than before dam construction (pre-1967) (p < 0.05), whereas summer peak flows (May–July) were significantly lower than before the dam showing that regulation has significantly altered seasonal flow regimes. During spring freshet and summer high flows, the Peace River strongly influenced the quality of the Slave River, as there were no significant differences in loadings of dissolved N, total P (TP), total organic C (TOC), total As, total Mn, total V, and turbidity and specific conductance between these rivers. In the Athabasca River, TP and specific conductance concentrations increased significantly since before oil sands developments (1967–2010), whereas dissolved N and sulfate have increased after the oil sands developments (1977–2010). Recently, the Athabasca River had significantly higher concentrations of dissolved N, TP, TOC, dissolved sulfate, specific conductance, and total Mn than either the Slave or the Peace Rivers during the winter months. The transboundary nature of the Peace, Athabasca, and Slave River basins has resulted in fragmented monitoring and reporting of the state of these rivers, and a more consistent monitoring framework is recommended.

Integr Environ Assess Manag 2013;9:405–425. © 2012 SETAC
Can natural variability trigger effects on fish and fish habitat as defined in Environment Canada's metal mining environmental effects monitoring program?
Authors: Mackey Robin , Rees Cassandra , Wells Kelly , Pham Samantha , England Kent
Published: August 2012

The Metal Mining Effluent Regulations (MMER) took effect in 2002 and require most metal mining operations in Canada to complete environmental effects monitoring (EEM) programs. An “effect” under the MMER EEM program is considered any positive or negative statistically significant difference in fish population, fish usability, or benthic invertebrate community EEM-defined endpoints. Two consecutive studies with the same statistically significant differences trigger more intensive monitoring, including the characterization of extent and magnitude and investigation of cause. Standard EEM study designs do not require multiple reference areas or preexposure sampling, thus results and conclusions about mine effects are highly contingent on the selection of a near perfect reference area and are at risk of falsely labeling natural variation as mine related “effects.” A case study was completed to characterize the natural variability in EEM-defined endpoints during preexposure or baseline conditions. This involved completing a typical EEM study in future reference and exposure lakes surrounding a proposed uranium (U) mine in northern Saskatchewan, Canada. Moon Lake was sampled as the future exposure area as it is currently proposed to receive effluent from the U mine. Two reference areas were used: Slush Lake for both the fish population and benthic invertebrate community surveys and Lake C as a second reference area for the benthic invertebrate community survey. Moon Lake, Slush Lake, and Lake C are located in the same drainage basin in close proximity to one another. All 3 lakes contained similar water quality, fish communities, aquatic habitat, and a sediment composition largely comprised of fine-textured particles. The fish population survey consisted of a nonlethal northern pike (Esox lucius) and a lethal yellow perch (Perca flavescens) survey. A comparison of the 5 benthic invertebrate community effect endpoints, 4 nonlethal northern pike population effect endpoints, and 10 lethal yellow perch effect endpoints resulted in the observation of several statistically significant differences at the future exposure area relative to the reference area and/or areas. When the data from 2 reference areas assessed for the benthic invertebrate community survey were pooled, no significant differences in effect endpoints were observed. These results demonstrate weaknesses in the definition of an “effect” used by the MMER EEM program and in the use of a single reference area. Determination of the ecological significance of statistical differences identified as part of EEM programs conducted during the operational period should consider preexisting (background) natural variability between reference and exposure areas. Integr Environ Assess Manag 2013; 9: 155–163. © 2012 SETAC
Differential entropy in wavelet sub‐band for assessment of glaucoma
Authors: Nath Malaya Kumar , Dandapat Samarendra
Published: August 2012

Glaucoma is an eye disease that causes progressive optic neuropathy and vision loss due to degeneration of the optic nerves. Cup to disc ratio (CDR) is the standard measure for evaluation of glaucoma. It is difficult to estimate the value of CDR if the boundaries of cup and disc are not well defined. In this work, we propose a novel method based on differential entropy (DE) for evaluation of glaucoma. DE can be used as a measure of glaucoma as it is proportional to the probability of number of glaucoma pixels in wavelet sub‐bands. It has been shown that DE or negentropy value of 0.25 as an optimum threshold for glaucoma detection. This method is evaluated and its performance is compared with three existing methods using 54 retinal images. The proposed method shows the best result with an accuracy value of 92.59%. © 2012 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 22, 161–165, 2012
A method for the visual analysis of early‐stage Parkinson's disease based on virtual MRI‐derived SPECT images
Authors: Chauvie Stephane , Obertino Margherita , Papaleo Alberto , Ruspa Marta , Solano Ada , Gozzoli Luigi , Gagliano Attilio , Biggi Alberto
Published: August 2012

Objective: Nuclear medicine imaging of dopamine transporter (DAT) binding is used in the differential diagnosis of neurodegenerative Parkinsonism but DAT receptor density in the posterior part of the putamens is of difficult evaluation because it is strongly affected by the partial‐volume effect. Since its quantitative correction is often difficult, we propose here a qualitative method to compare the real study to virtual images of the patient, obtained as if he/she was healthy. Method: The virtual images are obtained coregistering the magnetic resonance images to SPECT's; segmenting magnetic resonance images to obtain the real shape and position of caudates and putamens; digitally filling these volumes with an activity concentration close to normal condition; blurring and convolving images with the measured point‐spread function of the SPECT system. Result: The method was applied to phantom and, retrospectively, to a small cohort of 20 patients, that underwent SPECT examination more than 3 years ago, to prove the feasibility of the method in a clinical environment. Conclusions: This method enhances the accuracy of the nuclear medicine interpretation by the inclusion of the proper morphological information of each patient, helping the physician to differentiate between partial‐volume effects and real hypofixation of the tracer. The method proved to be feasible but is applicability is fostered by the need of a concomitant MR. © 2012 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 22, 172–176, 2012
Unraveling toxicological mechanisms and predicting toxicity classes with gene dysregulation networks
Authors: Pronk Tessa E. , van Someren Eugene P. , Stierum Rob H. , Ezendam Janine , Pennings Jeroen L.A.
Published: August 2012

The use of genes for distinguishing classes of toxicity has become well established. In this paper we combine the reconstruction of a gene dysregulation network (GDN) with a classifier to assign unseen compounds to their appropriate class. Gene pairs in the GDN are dysregulated in the sense that they are linked by a common expression pattern in one class and differ in this pattern in another class. The classifier gives a quantitative measure on this difference by its prediction accuracy. As an in‐depth example, gene pairs were selected that were dysregulated between skin cells treated with either sensitizers or irritants. Pairs with known and novel markers were found such as HMOX1 and ZFAND2A, ATF3 and PPP1R15A, OXSR1 and HSPA1B, ZFP36 and MAFF. The resulting GDN proved biologically valid as it was well‐connected and enriched in known interactions, processes and common regulatory motifs for pairs. Classification accuracy was improved when compared with conventional classifiers. As the dysregulated patterns for heat shock responding genes proved to be distinct from those of other stress genes, we were able to formulate the hypothesis that heat shock genes play a specific role in sensitization, apart from other stress genes. In conclusion, our combined approach creates added value for classification‐based toxicogenomics by obtaining novel, well‐distinguishing and biologically interesting measures, suitable for the formulation of hypotheses on functional relationships between genes and their relevance for toxicity class differences. Copyright © 2012 John Wiley & Sons, Ltd.
Ghrelin and toxicity: recent findings and future challenges
Authors: Vasileiou Ioanna , Patsouras Demetrios , Patsouris Efstratios , Theocharis Stamatios
Published: August 2012

Ghrelin is a novel brain–gut peptide that plays various roles in mammals, including control of food intake and growth hormone release, as well as gastric motility and acid secretion in the gastrointestinal tract. It is mainly secreted by the gastric mucosa, but is also expressed in various other tissues. Different studies confirm the multiple biological roles of and possible protective effects of ghrelin. Multiple in vitro and in vivo studies support the powerful protective action of ghrelin against heart, gastric and liver injury. Moreover, ghrelin has been reported to be beneficial in renal tissue injury and excretory function after ischemia–reperfusion and to exert neuroprotective effects in cerebral ischemic regions. The aim of this review is to summarize and evaluate all the currently available in vivo and in vitro studies regarding the effects of ghrelin on tissue injury induced in different organs and tissues. Copyright © 2012 John Wiley & Sons, Ltd.
Chemoinformatics and chemical genomics: potential utility of in silico methods
Authors: Valerio Luis G. , Choudhuri Supratim
Published: August 2012

Computational life sciences and informatics are inseparably intertwined and they lie at the heart of modern biology, predictive quantitative modeling and high‐performance computing. Two of the applied biological disciplines that are poised to benefit from such progress are pharmacology and toxicology. This review will describe in silico chemoinformatics methods such as (quantitative) structure–activity relationship modeling and will overview how chemoinformatic technologies are considered in applied regulatory research. Given the post‐genomics era and large‐scale repositories of omics data that are available, this review will also address potential applications of in silico techniques in chemical genomics. Chemical genomics utilizes small molecules to explore the complex biological phenomena that may not be not amenable to straightforward genetic approach. The reader will gain the understanding that chemoinformatics stands at the interface of chemistry and biology with enabling systems for mapping, statistical modeling, pattern recognition, imaging and database tools. The great potential of these technologies to help address complex issues in the toxicological sciences is appreciated with the applied goal of the protection of public health. Published 2012. This article is a US Government work and is in the public domain in the USA.
Facile graft of poly(2‐methacryloyloxyethyl phosphorylcholine) onto Fe3O4 nanoparticles by ATRP: Synthesis, properties, and biocompatibility
Authors: Sun Xiao‐Yan , Yu Shou‐Shan , Wan Jia‐Qi , Chen Ke‐Zheng
Published: August 2012

Magnetite (Fe3O4) nanoparticles with the surface hydroxyl groups were achieved by a polyol process. Using 2‐(4‐chlorosulfonylphenyl) ethyltrichlorosilane (CTCS) as initiator, 2‐(methacryloyloxy)ethyl phosphorylcholine (MPC) as monomer, poly(2‐(methacryloyloxy)ethyl phosphorylcholine) (PMPC)‐grafted Fe3O4 nanoparticles (MNP) were successfully prepared via the atom transfer radical polymerization (ATRP) method. The successful grafting of PMPC on the Fe3O4 nanoparticles surface was ascertained from the FTIR analysis. The modified nanoparticles (MNP‐CTCS‐PMPC) showed a good biocompatibility in the cytotoxicity test in vitro. Performance testing of MNP‐CTCS‐PMPC was performed through magnetic resonance analysis (MR), and its r2/r1 value was 24.1. These results indicated that the modified Fe3O4 nanoparticles would be a potential MRI contrast reagent. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2013.
Characterization of leukemic cell behaviors in a soft marrow mimetic alginate hydrogel
Authors: Vu Thao Thi Thu , Lim Carine , Lim Mayasari
Published: August 2012

Alginate hydrogels possess tunable mechanical properties that can mimic soft marrow tissue and present three‐dimensional (3D) cues. This study evaluates its utility for supporting leukemic cell growth in vitro and its impact on cell survival, growth, and differentiation. Our results showed that the standard viscosity alginates had compromised leukemia cell viability but lower viscosity alginates recovered cell viability and improved 3D cell proliferation (27 fold) compared to 2D cultures (18 fold). Conjugation with RGD peptides promoted further cell growth (43 folds). In general, 3D hydrogels supported high‐density cultures better than 2D cultures. Leukemic cells formed densely packed cell clusters in alginate hydrogels and spontaneously differentiated into a more diverse myeloid population. The cell cycle data suggested that more cells go into active cycling with a G2/M arrest in alginate hydrogels and the presence of multiploidy confirmed maturation toward megakaryocytes. In summary, superior culture of leukemia cells in 3D hydrogels is demonstrated in this study accompanied by a potential role of physical cues influencing cell fate decision. Manipulation of biophysical and biochemical properties of alginate hydrogels permits the study of specific interactions and serves to provide a robust 3D platform for studying extrinsic contributions inside the bone marrow. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2012.
Cancerous ovarian stem cells: Obscure targets for therapy but relevant to chemoresistance
Authors: Ahmed Nuzhat , Abubaker Khalid , Findlay Jock , Quinn Michael
Published: August 2012

Chemotherapy with platinum and taxanes is the first line of treatment for all epithelial ovarian cancer (EOC) patients after debulking surgery. Even though the treatment is initially effective in 80% of patients, recurrent cancer is inevitable in the vast majority of cases. Emerging evidence suggests that some tumor cells can survive chemotherapy by activating the self‐renewal pathways resulting in tumor progression and clinical recurrence. These defined population of cells commonly termed as “cancer stem cells” (CSC) may generate the bulk of the tumor by using differentiating pathways. These cells have been shown to be resistant to chemotherapy and, to have enhanced tumor initiating abilities, suggesting CSCs as potential targets for treatment. Recent studies have introduced a new paradigm in ovarian carcinogenesis which proposes in situ carcinoma at the fimbrial end of the fallopian tube to generate high‐grade serous ovarian carcinomas, in contrast to ovarian cortical inclusion cysts (CIC) which produce borderline and low grade serous, mucinous, endometrioid, and clear cell carcinomas. This review summarizes recent advances in our understanding of the cellular origin of EOC and the molecular mechanisms defining the basis of CSC in EOC progression and chemoresistance. Using a model ovarian cancer cell line, we highlight the role of CSC in response to chemotherapy, and relate how CSCs may impact on chemoresistance and ultimately recurrence. We also propose the molecular targeting of CSCs and suggest ways that may improve the efficacy of current chemotherapeutic regimens needed for the management of this disease. J. Cell. Biochem. 114: 21–34, 2012. © 2012 Wiley Periodicals, Inc.
SIMONA 1.0: An efficient and versatile framework for stochastic simulations of molecular and nanoscale systems
Authors: Strunk T. , Wolf M. , Brieg M. , Klenin K. , Biewer A. , Tristram F. , Ernst M. , Kleine P. J. , Heilmann N. , Kondov I. , Wenzel W.
Published: August 2012

Molecular simulation methods have increasingly contributed to our understanding of molecular and nanoscale systems. However, the family of Monte Carlo techniques has taken a backseat to molecular dynamics based methods, which is also reflected in the number of available simulation packages. Here, we report the development of a generic, versatile simulation package for stochastic simulations and demonstrate its application to protein conformational change, protein–protein association, small‐molecule protein docking, and simulation of the growth of nanoscale clusters of organic molecules. Simulation of molecular and nanoscale systems (SIMONA) is easy to use for standard simulations via a graphical user interface and highly parallel both via MPI and the use of graphical processors. It is also extendable to many additional simulations types. Being freely available to academic users, we hope it will enable a large community of researchers in the life‐ and materials‐sciences to use and extend SIMONA in the future. SIMONA is available for download under http://int.kit.edu/nanosim/simona. © 2012 Wiley Periodicals, Inc.
Leader Positivity and Follower Creativity: An Experimental Analysis
Authors: Avey James B. , Lynn Richmond F. , Nixon Don R.
Published: August 2012

Using an experimental research design, 191 working adults were randomly assigned to two experimental conditions in order to test a theoretical model linking leader and follower positive psychological capital (PsyCap). Multiple methods were used to gather information from the participants. We found when leader PsyCap was manipulated experimentally, it was positively related to follower PsyCap. Subsequently, follower PsyCap was significantly related to employee's originality of ideas; one important component of creativity in the workplace. We discuss the theoretical contributions of linking leader and follower PsyCap in what emerges as a directional contagion effect, and the mediating role of follower PsyCap in enhancing follower creative task performance. Further, employee selection and development as well as leadership development practical implications are discussed. We conclude with a discussion of limitations and future research directions.
Measuring Functional Creativity: Non‐Expert Raters and the Creative Solution Diagnosis Scale
Authors: Cropley David H. , Kaufman James C.
Published: August 2012

The Creative Solution Diagnosis Scale (CSDS) is a 30‐item scale based on a core of four criteria: Relevance & Effectiveness, Novelty, Elegance, and Genesis. The CSDS offers potential for the consensual assessment of functional product creativity. This article describes an empirical study in which non‐expert judges rated a series of mousetrap designs using the 30‐item CSDS. A confirmatory factor analysis revealed a simple structure that corresponded closely to the a priori theoretical model of functional creativity, resulting in a revised 24‐item CSDS. Non‐expert judges were able to use the scale with a high degree of reliability and internal consistency. The revised CSDS paves the way for further research into the use of non‐expert judges as a possible replacement for more costly, harder‐to‐obtain experts when measuring product creativity using the Consensual Assessment Technique (CAT).
Interferon gamma and T cells inhibit osteogenesis induced by allogeneic mesenchymal stromal cells
Authors: Dighe Abhijit S. , Yang Scott , Madhu Vedavathi , Balian Gary , Cui Quanjun
Published: August 2012

The mesenchymal stromal cells (MSCs) are reported to be immunoprivileged and osteogenic. We hypothesized that the use of allogeneic MSCs for bone repair was possible if they displayed an ability to induce similar osteogenesis in syngeneic as well as in allogeneic hosts. To test this hypothesis we used a cloned bone marrow derived cell, termed D1, isolated from Balb/c mice. The D1 cells were subcutaneously injected in syngeneic Balb/c, allogeneic immunocompetent B6, allogeneic T‐cell deficient NCr nude, and allogeneic B6 Pfp−/− Rag2−/− mice that lack matured T and B cells as well as NK‐cell cytolytic functions. D1 cells formed ectopic bones only in syngeneic or allogeneic immunocompromised hosts but not in allogeneic B6 hosts. The lack of T cells alone in allogeneic NCr mice was sufficient to promote osteogenesis in allogeneic environment. We observed a significantly higher number of T cells, B cells, macrophages and significantly higher expression of interferon gamma (IFN‐γ) in B6 allogeneic implants as compared to the syngeneic implants. These factors correlated with severe inhibition of expression of alkaline phosphatase, osteocalcin, and runx2 genes in the implants from B6 mice. Our data suggest that strategies to inhibit T cells and IFN‐γ functions will be useful for bone repair mediated by allogeneic MSCs. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 227–234, 2013
Inhibition of MEK pathway in vestibular schwannoma cell culture
Authors: Neff Brian A. , Voss Stephen G. , Schmitt William R. , Driscoll Colin L. W. , Link Michael J. , Beatty Charles W. , Kita Hirohito
Published: August 2012

Objectives/Hypothesis:

The purpose of this study was to evaluate the Ras GTPase (Ras) to extracellular signal‐regulated kinase (ERK) pathway in vestibular schwannoma (VS) cell cultures and patient excised schwannoma tumors. Mitogen‐activated protein kinase kinase (MEK) inhibitor CI‐1040 (PD184352) was utilized to evaluate the effect of specific MEK inhibition on benign schwannoma cell culture proliferation and apoptosis.

Study Design:

Prospective evaluation of human schwannoma cell lines and tumors.

Methods:

Western blotting was completed with phospho‐antibodies for proteins in the Ras‐ERK pathway. Increasing concentrations of CI‐1040 were utilized in schwannoma cell cultures to evaluate cell proliferation and apoptosis. Proliferation was measured with the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyl tetrazolium bromide proliferation assay, and apoptosis was monitored with flow cytometry of annexin V/propidium iodide‐stained cells.

Results:

The most consistent Ras‐ERK pathway alterations were found in phospho‐MEK and ERK. Phospho‐MEK was not overexpressed in the schwannoma cell lines, but six out of 10 VS showed significant increases compared to benign Schwann cell controls. Similarly, nine of 10 VS tumors showed increased phospho‐ERK expression. CI‐1040 showed significantly reduced schwannoma cell proliferation at the 50 and 100 μM (IC50 20 μM and 30 μM) concentrations when compared to carrier only controls in two out three schwannoma cell lines. The remaining schwannoma cell line was relatively refractory to the antiproliferative effects of CI‐1040 at doses up to 100 μM (IC50 58 μM). Cumulative data of four separate schwannoma cell lines demonstrated that apoptosis was increased in treated schwannoma cells at CI‐1040 concentrations of 50 and 100 μM at 72 hours.

Conclusions:

There is overexpression of phosphorylated (activated) proteins in the Ras‐ERK pathway in schwannoma cultures and tumors as compared to benign human Schwann cell culture controls. MEK inhibitor, CI‐1040, created significantly decreased schwannoma cell proliferation and increased apoptosis in cell culture. These data justify the use of MEK inhibitors in animal treatment studies of VS.
Tinnitus in children: Association with stress and trait anxiety
Authors: Kim Young Ho , Jung Hahn Jin , Kang Seong Il , Park Kyung Tae , Choi Jung‐Seok , Oh Seung‐Ha , Chang Sun O
Published: August 2012

Objectives/Hypothesis:

The aim of this study was to investigate associations between tinnitus and stress factors including anxiety in elementary school students.

Study Design:

Cross‐sectional study.

Methods:

We conducted a cross‐sectional questionnaire survey in 940 students aged from 10 to 12 years. Data on 928 students were collected. The questionnaire comprised 96 questions that were classified into six categories: subjects' symptoms, stress factors, State Anxiety (transitory emotional condition characterized by feeling of tension and apprehension) Inventory for Children (SAIC), Trait Anxiety (general tendency to respond with anxiety to environmental threat) Inventory for Children (TAIC), visual analog scale of tinnitus, and Tinnitus Handicap Inventory (THI).

Results:

Four hundred thirty‐five students (46.9%) had experienced tinnitus more than once, and 41 (4.4%) suffered from it continuously. Self‐perception of hearing loss, dizziness, headache, and concerns about obesity had significant differences between tinnitus and nontinnitus groups, whereas other stress factors did not show any difference. TAIC scores showed statistically significant differences according to the frequency of tinnitus in children experiencing tinnitus, whereas SAIC scores did not. Annoyance, influence on daily life, disturbance of sleep, and study by tinnitus and THI scores showed significant differences according to the frequency of tinnitus.

Conclusions:

The present study confirms that many children are aware of tinnitus and that they may be susceptible to stressful environments. In particular, trait anxiety may be associated with tinnitus. Because both tinnitus and anxiety can affect the daily lives and health of children—as with adults—a detailed strategy for the management of tinnitus in children should be established.
Phytosterols and steryl esters in diverse Cucurbita, Cucumis and Citrullus seed oils
Authors: Oelschlägel Stefanie , Menzel Carolin , Speer Karl
Published: August 2012

Δ7‐Phytosterols present in pumpkin seed oil are significant for the prevention of prostate disorders. Herbal medicines are increasingly offered as dried kernels or concentrated ethanolic extracts of Cucurbita pepo seeds. Until now, the pumpkin seeds of C. pepo have almost exclusively been used for this purpose. Only a few data concerning the sterol content of other Cucurbitoideae seeds are available. Therefore, we isolated, identified, and quantified the free and esterified phytosterols of 12 Cucurbita, 3 Cucumis, and 3 Citrullus seed oils. The total sterol content of these seeds ranged from 297 mg per 100 g oil in Cucurbita maxima ‘Turk's Turban’ to 814 mg per 100 g oil in Citrullus lanatus ‘Sugar Baby Watermelon’, equivalent to 64 to 193 mg per 100 g seeds respectively. These were mainly Δ7‐sterols (˜82%) with the steryl esters acounting for ˜32% of the total sterol content.
Understanding the switchbacks: The impact of direct antivirals on the minimization of hepatitis C virus recurrence after transplantation
Authors: Mutimer David
Published: August 2012

Key Points

1. Interferon (IFN) and ribavirin can be used in select patients before or after liver transplantation, and they can reduce the risk of recurrence or effect a cure in these settings.

2. Currently licensed direct-acting antiviral drugs are used with IFN and ribavirin, so the safety and tolerability of triple therapy will be worse than those of double therapy in pretransplant and posttransplant settings.

3. Drug-drug interactions [exemplified by the interactions of protease inhibitors (PIs) with tacrolimus and cyclosporine] and the need for dose modifications (exemplified by the need to modify ribavirin doses in patients with renal dysfunction) challenge the safe use of antiviral drugs after transplantation.

4. Experience with the use of human immunodeficiency virus PIs and emerging data about hepatitis C virus (HCV) PIs show that this class of drugs can be used with care after transplantation.

5. Attempts to prevent HCV graft infections through the use of HCV immunoglobulin immediately after transplantation have been largely unsuccessful.

6. The blockade of cell surface HCV receptors with antibodies or small molecules appears to limit HCV cell entry in vivo and in a mouse model, and this may suggest a novel approach to limiting HCV recurrence at the time of transplantation. Liver Transpl, 2012. © 2012 AASLD.
Progressive graft fibrosis and donor-specific human leukocyte antigen antibodies in pediatric late liver allografts
Authors: Miyagawa-Hayashino Aya , Yoshizawa Atushi , Uchida Yoichiro , Egawa Hiroto , Yurugi Kimiko , Masuda Satohiro , Minamiguchi Sachiko , Maekawa Taira , Uemoto Shinji , Haga Hironori
Published: August 2012

The role of donor-specific anti-human leukocyte antigen antibodies (DSAs) that develop late after living donor liver transplantation is unknown. Seventy-nine pediatric recipients who had good graft function and underwent protocol liver biopsy more than 5 years after transplantation (median = 11 years, range = 5-20 years) were reviewed. DSAs were determined with the Luminex single-antigen bead assay at the time of the last biopsy, and complement component 4d (C4d) immunostaining was assessed at the times of the last biopsy and the previous biopsy. The donor specificity of antibodies could be identified in 67 patients: DSAs were detected in 32 patients (48%), and they were usually against human leukocyte antigen class II (30 cases) but were rarely against class I (2 cases). These patients had a higher frequency of bridging fibrosis or cirrhosis (28/32 or 88%) than DSA-negative patients (6/35 or 17%, P < 0.001). Fibrosis was likely to be centrilobular-based. DSA-positive patients, in comparison with DSA-negative patients, had higher frequencies of diffuse/focal endothelial C4d staining (P < 0.001) and mild/indeterminate acute rejection [15/32 (47%) versus 5/35 (14%), P = 0.004]. Four DSA-negative patients were off immunosuppression, whereas no patients in the DSA-positive group were (P = 0.048). In conclusion, the high prevalence of graft fibrosis and anti–class II DSAs in late protocol biopsy samples suggests that humoral alloreactivity may contribute to the process of unexplained graft fibrosis late after liver transplantation. Liver Transpl 18:1333–1342, 2012. © 2012 AASLD.
Lagrangian for the convection–diffusion equation
Authors: Cresson Jacky , Greff Isabelle , Inizan Pierre
Published: August 2012

Using the asymmetric fractional calculus of variations, we derive a fractional Lagrangian variational formulation of the convection–diffusion equation in the special case of constant coefficients. Copyright © 2012 John Wiley & Sons, Ltd.
Classification of single‐voxel 1H spectra of childhood cerebellar tumors using lcmodel and whole tissue representations
Authors: Raschke Felix , Davies Nigel P. , Wilson Martin , Peet Andrew C. , Howe Franklyn A.
Published: August 2012

In this study, mean tumor spectra are used as the basis functions in LCModel to create a direct classification tool for short echo time 1H magnetic resonance spectroscopy of pediatric brain tumors. LCModel is a widely used analysis tool designed to fit a linear combination of individual metabolite spectra to in vivo spectra. Here, we have used LCModel to fit mean spectra and corresponding variability components of childhood cerebellar tumors, as calculated using principal component analysis, and assessed for classification accuracy. Classification was performed according to the highest estimated tumor proportion. This method was tested in a leave‐one‐out analysis discriminating between pediatric brain tumor spectra of medulloblastoma vs. pilocytic astrocytoma and medulloblastoma vs. pilocytic astrocytoma vs. ependymoma. Additionally, the effect of accepting different Cramér‐Rao Lower Bound cut‐off criteria on classification accuracy and estimated tissue proportions was investigated. The best classification results differentiating medulloblastoma vs. pilocytic astrocytoma and medulloblastoma vs. pilocytic astrocytoma vs. ependymoma were 100 and 87.7%, respectively. These results are comparable to a specialized pattern recognition analysis of this data set and give easy to interpret results in the form of estimated tissue proportions. The method requires minimal user input and is easily transferable across sites and to other magnetic resonance spectroscopy classification problems. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
Nerve ultrasound in a case of chronic inflammatory demyelinating neuropathy
Authors: Kerasnoudis Antonios
Published: August 2012

Introduction: Chronic inflammatory demyelinating polyneuropathy (CIDP) is the most common acquired immune‐mediated inflammatory disorder of the peripheral nervous system. The diagnosis is based mainly on the clinical presentation and electrophysiological detection of demyelination. Methods: Several MRI studies have demonstrated hypertrophy and abnormal enhancement of spinal nerve roots or brachial plexus in CIDP, but there have been only anecdotal reports of similar sonographic findings. Results: This article reports the sonographic findings of a CIDP case and includes a review of the literature and previously reported cases. Conclusions: This case report highlights the importance of sonography in the localization and recognition of focal nerve enlargements in patients with CIDP. This method could be a helpful tool in the diagnosis of conduction block in CIDP, especially in cases where a nerve segment cannot be explored easily with the inching technique. Systematic data are needed to confirm this observation. Muscle Nerve 47:443‐446, 2013
A throughput‐optimized array system for multiple‐mouse MRI
Authors: Ramirez Marc S. , Lai Stephen Y. , Bankson James A.
Published: August 2012

MRI is a versatile tool for the systematic assessment of anatomical and functional changes in small‐animal models of human disease. Its noninvasive nature makes it an ideal candidate for longitudinal evaluations of disease progression, but relatively long scan times limit the number of observations that can be made in a given interval of time, imposing restrictions on experimental design and potentially compromising statistical power. Methods that reduce the overall time required to scan multiple cohorts of animals in distinct experimental groups are therefore highly desirable. Multiple‐mouse MRI, in which several animals are simultaneously scanned in a common MRI system, has been successfully used to improve study throughput. However, to best utilize the next generation of small‐animal MRI systems that will be equipped with an increased number of receive channels, a paradigm shift from the simultaneous scanning of as many animals as possible to the scanning of a more manageable number, at a faster rate, must be considered. This work explores the tradeoffs between the number of animals to scan at once and the number of array elements dedicated to each animal, to maximize throughput in systems with 16 receive channels. An array system consisting of 15 receive and five transmit coils allows acceleration by a combination of multi‐animal and parallel imaging techniques. The array system was designed and fabricated for use on a 7.0‐T/30‐cm Bruker Biospec MRI system, and tested for high‐throughput imaging performance in phantoms and live mice. Results indicate that up to a nine‐fold throughput improvement of a single sequence is possible compared with an unaccelerated single‐animal acquisition. True data throughput of a contrast‐enhanced anatomical study is estimated to be improved by just over six‐fold. Copyright © 2012 John Wiley & Sons, Ltd.
Proton pump inhibitors and traditional nonsteroidal anti‐inflammatory drugs and the risk of acute interstitial nephritis and acute kidney injury
Authors: Leonard Charles E. , Freeman Cristin P. , Newcomb Craig W. , Reese Peter P. , Herlim Maximilian , Bilker Warren B. , Hennessy Sean , Strom Brian L.
Published: August 2012

Purpose

This study aims to examine the associations between proton pump inhibitors (PPIs), traditional nonsteroidal anti‐inflammatory drugs (tNSAIDs), PPI + tNSAID co‐exposure, and the development of the following: (i) acute interstitial nephritis (AIN), a specific kidney injury often attributed to these drugs, and (ii) acute kidney injury (AKI), a general kidney injury encompassing AIN.

Methods

Two retrospective case–control studies were conducted, one for each outcome, within the General Practice Research Database. Cases were diagnostic‐coded AIN (primary outcome) or AKI (secondary outcome) events. Controls were matched on age, sex, and general practitioner practice. Exposures were defined by the presence/absence of the following mutually exclusive therapies on the index date: (i) PPI alone; (ii) tNSAID alone; (iii) PPI + tNSAID; or (iv) neither PPI nor tNSAID (referent).

Results

Sixty‐eight AIN cases and 3347 controls were identified. The adjusted odds ratios (ORs) for PPI and tNSAID exposures alone were 3.20 (0.80–12.79) and 1.90 (0.65–5.51), respectively. Numerous sensitivity analyses produced adjusted ORs for AIN between 3.0 and 7.7, and 1.6 and 1.9, respectively. We identified 27 982 AKI cases and 1 323 850 controls. The adjusted ORs for PPI alone, tNSAID alone, and PPI + tNSAID exposures were 1.05 (0.97–1.14), 1.31 (1.25–1.37), and 1.33 (1.07–1.64), respectively. Numerous sensitivity analyses produced adjusted ORs for AKI between 1.0 and 1.1, 1.1 and 1.3, and 1.3 and 1.4, respectively.

Conclusions

Proton pump inhibitor exposure may increase the odds of AIN, but this result was not definitive and should be confirmed in a dataset with more AIN cases to allow for increased statistical precision. tNSAIDs, yet not PPIs, were associated with a significantly increased odds of AKI. Copyright © 2012 John Wiley & Sons, Ltd.
Synthesis and properties of novel high oil‐absorbing resin based on poly(ethylene‐propylene‐diene/ α‐methylstyrene/itaconic acid)
Authors: Zhou Xiao‐Ming , Chuai Cheng‐Zhi
Published: August 2012

A novel high oil‐absorbing resin, P(EPDM/α‐MSt/ITA), was synthesized by suspension copolymerization with ethylene‐propylene‐diene (EPDM), α‐methylstyrene (α‐MSt), and itaconic acid (ITA) as monomers, benzoyl peroxide as initiator, and divinylbenzene as crosslink agent in this study. By using methods such as infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy, we studied the oil‐absorbing resin structure, oil‐absorption rate, oil‐absorption saturation time, and submicroscopic structure of oil‐absorption resin after oil absorption. The experiment results show that the highest oil absorptivity of the resin was about 21.9 g/g in diesel oil, obviously increasing the oil absorptive properties by the addition of itaconic acid as reaction monomer. We can draw a conclusion from scanning electron microscopy observation of sample after oil absorption that the oil‐absorption resin was filled with diesel oil, and a kind of morphology structure similar with embossment can be produced during the oil‐absorbing process. The oil‐absorbing resin was used repeatedly through the extraction by ethanol. Experiment result proved to have little effect on oil‐absorption properties. Otherwise, the oil‐absorption rate constant K of novel high oil‐absorbing resin was evaluated for diesel oil, and the oil‐absorbing process obeyed the first‐order kinetics equation. POLYM. ENG. SCI. 2013. © 2012 Society of Plastics Engineers
Structure and performance of temperature‐sensitive poly(vinylidene fluoride) hollow fiber membrane fabricated at different take‐up speeds
Authors: Shen Xiang , Zhao Yiping , Chen Li , Feng Xia , Yang Duo , Zhang Qiang , Su Dan
Published: August 2012

Graft copolymer (PVDF‐g‐PNIPAAm) having poly(vinylidene fluoride) (PVDF) backbones and poly(N‐isopropylacrylamide) (PNIPAAm) side chains was synthesized via radical copolymerization and its hollow fiber membrane was fabricated from dry–wet spinning technique with N, N‐dimethylformamide as the solvent and poly(ethylene glycol) (10,000) as the additive. The effects of spinning condition (take‐up speeds) on the structures and performances of resulting fiber membranes were systematically considered. The structures and performances of fiber membranes were characterized by element analysis, X‐ray photoelectron spectroscopy, water contact angle measurement, scanning electron microscope, atom force microscope, and filtration experiments. The results indicate that PNIPAAm side chains tended to enrich on the membrane surface and pore surface and especially tended to aggregate on the inner surface due to the effect of bore fluid. The hollow fiber membrane exhibits an obvious temperature‐sensitive property. The pure water flux increases remarkably around 32°C, while the retention of albumin egg decreases accordingly, when the permeation temperature rises from 20 to 45°C. As the take‐up speed increases, both the inner and outer diameters of fiber membranes decrease. A higher take‐up speed favors higher pure water permeation flux, which allows larger molecules to permeate through the fiber membrane. POLYM. ENG. SCI. 2013. © 2012 Society of Plastics Engineers
The preparation and adsorption properties of electrospun aramid nanofibers
Authors: Wei Zhimei , Zhang Quanchao , Wang Lihua , Peng Minle , Wang Xiaojun , long Shengru , Yang Jie
Published: August 2012

The focus of this work is the preparation of aramid nanofibers via electrospinning technology and the study of their adsorption properties. In this article, aramid nanofibers were prepared by electrospinning aramid fibers solution with the addition of lithium chloride (LiCl). It showed a good adsorption capacity when methylene blue (MB) was used as the model target. There were much larger adsorption amounts and faster kinetics of uptaking target species of electrospun aramid nanofibers to MB than that of electrospun polyethersulfone (PES) nanofibers. Compared with activated carbon, aramid nanofibers also have a much faster adsorption rate to MB. Aramid nanofibers were subsequently used to effectively remove endocrine disruptors such as bisphenol A (BPA), phenol (Phe), and p‐hydroquinone (BPhe) from their aqueous solutions. Additionally, molecule imprinted technology enhances aramid nanofibers with much higher adsorption amounts and special adsorption property for endocrine disruptors. These results showed that aramid nanofibers have the potential to be used in environmental applications. © 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012