bluuebunny/crossref_metadata_2025 huggingface dataset:
1,2‐N‐Migration in a Gold‐Catalysed Synthesis of Functionalised Indenes by the 1,1‐Carboalkoxylation of Ynamides
Authors: Adcock Holly V. , Langer Thomas , Davies Paul W.
Published: May 2014

Unique α‐hemiaminal ether gold carbene intermediates were accessed by a gold‐catalysed 1,1‐carboalkoxylation strategy and evolved through a highly selective 1,2‐N‐migration. This skeletal rearrangement gave functionalised indenes, and isotopic labelling confirmed the rare CN bond cleavage of the ynamide moiety. The effect of substituents on the migration has been explored, and a model is proposed to rationalise the observed selectivity.
3‐Aminoazetidin‐2‐one Derivatives as N‐Acylethanolamine Acid Amidase (NAAA) Inhibitors Suitable for Systemic Administration
Authors: Fiasella Annalisa , Nuzzi Andrea , Summa Maria , Armirotti Andrea , Tarozzo Glauco , Tarzia Giorgio , Mor Marco , Bertozzi Fabio , Bandiera Tiziano , Piomelli Daniele
Published: May 2014

N‐Acylethanolamine acid amidase (NAAA) is a cysteine hydrolase that catalyzes the hydrolysis of endogenous lipid mediators such as palmitoylethanolamide (PEA). PEA has been shown to exert anti‐inflammatory and antinociceptive effects in animals by engaging peroxisome proliferator‐activated receptor α (PPAR‐α). Thus, preventing PEA degradation by inhibiting NAAA may provide a novel approach for the treatment of pain and inflammatory states. Recently, 3‐aminooxetan‐2‐one compounds were identified as a class of highly potent NAAA inhibitors. The utility of these compounds is limited, however, by their low chemical and plasma stabilities. In the present study, we synthesized and tested a series of N‐(2‐oxoazetidin‐3‐yl)amides as a novel class of NAAA inhibitors with good potency and improved physicochemical properties, suitable for systemic administration. Moreover, we elucidated the main structural features of 3‐aminoazetidin‐2‐one derivatives that are critical for NAAA inhibition.
Existence of Weak Solutions Up to Collision for Viscous Fluid‐Solid Systems with Slip
Authors: Gérard‐Varet David , Hillairet Matthieu
Published: May 2014

We study in this paper the movement of a rigid solid inside an incompressible Navier‐Stokes flow within a bounded domain. We consider the case where slip is allowed at the fluid/solid interface through a Navier condition. Taking into account slip at the interface is very natural within this model, as classical no‐slip conditions lead to unrealistic collisional behavior between the solid and the domain boundary. We prove for this model existence of weak solutions of Leray type, up to collision, in three dimensions. The key point is that, due to the slip condition, the velocity field is discontinuous across the fluid/solid interface. This prevents obtaining global H1 bounds on the velocity, which makes many aspects of the theory of weak solutions for Dirichlet conditions inappropriate. © 2014 Wiley Periodicals, Inc.
Fabrication of Carbon‐Felt‐Based Multi‐Enzyme Immobilized Anodes to Oxidize Sucrose for Biofuel Cells
Authors: Handa Yutaka , Yamagiwa Kiyofumi , Ikeda Yutaro , Yanagisawa Yuichi , Watanabe Shinya , Yabuuchi Naoaki , Komaba Shinichi
Published: May 2014

A carbon‐felt‐based multi‐enzyme immobilized bioanode for biofuel cells has been successfully developed. The combination of four enzymes, namely, invertase, mutarotase, glucose oxidase, and fructose dehydrogenase, makes it possible to use sucrose—a disaccharide—as fuel for the bioanode. The new electrode exhibits a high oxidation current density of about 12 mA cm−2 (0.25 V vs. Ag/AgCl) in a McIlvaine buffer solution containing sucrose at pH 6.0 in the half‐cell configuration. A sucrose/O2 biofuel cell composed of the bioanode and an opposite biocathode, including bilirubin oxidase as the enzymatic electrocatalyst, was fabricated, and the new device demonstrated a maximum power density of 2.90 mW cm−2 with an open‐circuit voltage of 0.69 V in the McIlvaine buffer solution. The biofuel cell fabricated using our multi‐enzyme anode operates in commercially available beverages that contain only sugar, even without glucose.
Enhanced Wave‐Absorption Properties of Nanocomposites Based on the Synthesized Bi2S3 Nanorods and Polyvinylidene Fluoride
Authors: Luo Xin , Wang Guang‐Sheng , Guo Hao‐Yue , Zhang Xiao‐Juan , Cao Wen‐Qiang , Wei Yun‐Zhao , Guo Lin , Cao Mao‐Sheng
Published: May 2014

In this study, Bi2S3 nanorods were synthesized on a large scale through a simple hydrothermal method at low temperature. To investigate the wave‐absorption properties of Bi2S3 nanorods, the homogeneous nanocomposites consisting of the nanorods and paraffin or polyvinylidene fluoride (PVDF) matrix were fabricated and characterized. The results indicated that the introduction of Bi2S3 nanorods to PVDF significantly enhanced the wave‐absorption properties of the absorber. The loss mechanism of Bi2S3/PVDF nanocomposites with different loadings was discussed and some theories were also employed to explain the mechanism of the enhancement based on the experimental results.
An analytical methodology for assessment of smart monitoring impact on future electric power distribution system reliability
Authors: Ahadi Amir , Ghadimi Noradin , Mirabbasi Davar
Published: May 2014

Smart grid is referred to a modernized power grid which can mitigate fault detection and allow self‐healing of the system without the intervention of operators. This article proposes an innovative analytical formulation using Markov method to evaluate electric power distribution system reliability in smart grids, which incorporates the impact of smart monitoring on the overall system reliability. An accurate reliability model of the main network components and the communication infrastructure have been also considered in the methodology. The proposed approach was applied to a well‐known test bed (Roy Billinton Test System) and various reliability case studies with monitoring provision and monitoring deficiency are analyzed. This article involves the developing possibilities of communication technologies and next‐generation control systems of the entire smart network based on the real‐time monitoring and modern control system to achieve a reliable, economical, safe, and high efficiency of electricity. The implementations indicate that using an appropriate set of the smart grid monitoring devices for power system components can virtually influence all the reliability indices although the amount of improvement varies between techniques. The proposed approach determined that smart monitoring for which components of the electric power distribution systems are tailored and deduce to major economical benefits. The described approach also reveals which reliability indices drastically influenced using monitoring. © 2014 Wiley Periodicals, Inc. Complexity 21: 99–113, 2015
Anti‐Inflammatory Activities of Melatonin Derivatives in Lipopolysaccharide‐Stimulated RAW 264.7 Cells and Antinociceptive Effects in Mice
Authors: Phiphatwatcharaded Chawapon , Topark‐Ngarm Acharawan , Puthongking Ploenthip , Mahakunakorn Pramote
Published: May 2014

Preclinical Research

This study describes the anti‐inflammatory activities of two semisynthesized melatonin (MT) derivatives, benzoyl‐melatonin (BMT) and acetyl‐melatonin (AMT), on the production of pro‐inflammatory mediators in lipopolysaccharide (LPS)‐stimulated macrophage cells (RAW 264.7) and their antinociceptive effects in mice. The MT derivatives inhibited production of nitric oxide NO and prostaglandin E2 in LPS‐stimulated RAW264.7 cells in a dose‐dependent manner with IC50 values lower than those of MT. BMT produced increased tail flick latency time, decreased number of writhes, and reduced nociceptive response in mice when compared with AMT and MT. BMT and AMT had enhanced anti‐inflammatory effects in LPS‐stimulated RAW264.7 compared with MT. However, in mouse studies BMT exhibited the highest potency as an anti‐inflammatory agent and was longer‐acting as an antinociceptive compound compared with AMT or MT, suggesting that BMT has potential as an anti‐inflammatory and analgesic compound.
High‐resolution mass spectrometric metabolite profiling of a novel synthetic designer drug, N‐(adamantan‐1‐yl)‐1‐(5‐fluoropentyl)‐1H‐indole‐3‐carboxamide (STS‐135), using cryopreserved human hepatocytes and assessment of metabolic stability with human liver microsomes
Authors: Gandhi Adarsh S. , Wohlfarth Ariane , Zhu Mingshe , Pang Shaokun , Castaneto Marisol , Scheidweiler Karl B. , Huestis Marilyn A.
Published: May 2014

N‐(Adamantan‐1‐yl)‐1‐(5‐fluoropentyl)‐1H‐indole‐3‐carboxamide (STS‐135) is a new synthetic cannabinoid in herbal incense products discussed on Internet drug user forums and identified in police seizures. To date, there are no STS‐135 clinical or in vitro studies identifying STS‐135 metabolites. However, characterizing STS‐135 metabolism is critical because synthetic cannabinoid metabolites can possess pharmacological activity and parent compounds are rarely detectable in urine.

To characterize the metabolite profile, human hepatocytes were incubated with 10 µmol/L STS‐135 for up to 3 h. High‐resolution mass spectrometry with software‐assisted data mining identified 29 STS‐135 metabolites. Less than 25% of STS‐135 parent compound remained after 3 h incubation. Primary metabolites were generated by mono‐, di‐ or trihydroxylation with and without ketone formation, dealkylation, and oxidative defluorination of N‐fluoropentyl side chain or possible oxidation to carboxylic acid, some of them further glucuronidated. Hydroxylations occurred mainly on the aliphatic adamantane ring and less commonly on the N‐pentyl side chain. At 1 h, phase I metabolites predominated, while at 3 h, phase II metabolites were present in higher amounts. The major metabolites were monohydroxy STS‐135 (M25) and dihydroxy STS‐135 (M21), both hydroxylated on the adamantane system. Moreover, metabolic stability of STS‐135 (1 µmol/L) was assessed in human liver microsomes experiments. The in vitro half‐life of STS‐135 was 3.1 ± 0.2 min and intrinsic clearance (CLint) was 208.8 mL · min−1 · kg−1.

This is the first report characterizing STS‐135 hepatic metabolic pathways. These data provide potential urinary targets to document STS‐135 intake in clinical and forensic settings and potential candidates for pharmacological testing. Copyright © 2014 John Wiley & Sons, Ltd.
Body image dissatisfaction among immigrant children and adolescents in Canada and the United States: A scoping review
Authors: Kimber Melissa , Couturier Jennifer , Georgiades Katholiki , Wahoush Olive , Jack Susan M.
Published: May 2014

Objective

To systematically summarize the literature examining body image dissatisfaction (BID) among immigrant children and adolescents living in Canada and the United States (US).

Method

Sources were identified by entering search terms into six electronic databases and by completing an electronic hand search of research journals focusing on body image. Eligible sources were those published between 1946 and November 2012, conducted within Canada or the US, included immigrant children or adolescents (<18 years), and measured BID through self‐report. Synthesis followed the principles of thematic and content analysis (Vaismoradi et al., Nurs Health Sci, 2013,15,398–405).

Results

A total of 12 sources were included in our synthesis, spanning years 1991 to 2010. These studies indicate that immigrant children and adolescents experience BID. However, the literature is plagued by a disproportionate focus on females, Latino/Hispanic immigrants, and inadequate attention to issues of measurement.

Discussion

There is no evidence about the BID experiences of immigrant children and adolescents in Canada and limited information has stemmed from the US. A more robust evidence‐base should include the use of advanced methods to examine the influence of acculturation and acculturative stress on BID among immigrant male and female children and adolescents. © 2014 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:892–897)
Pain prevalence and its determinants after spinal cord injury: A systematic review
Authors: van Gorp S. , Kessels A.G. , Joosten E.A. , van Kleef M. , Patijn J.
Published: May 2014

Pain prevalence studies are important as they illustrate the magnitude of pain problems in a certain patient population, such as patients living with a spinal cord injury (SCI). Strikingly, reported pain prevalence rates in SCI patients are found to vary greatly, while determinants for the differences between pain prevalence reports remain unclear. We here aim to identify determinants for the differences (heterogeneity) in pain prevalence reports through a systematic review of all SCI pain prevalence reporting studies. Literature search was done using Medline, Cumulative Index to Nursing and Allied Health Literature, ISI Web of Knowledge and Embase. Data abstraction was performed while blinded and was followed by meta‐(regression)‐analyses. We identified 82 studies. Study design‐related determinants of SCI pain prevalence reports were pain definition strictness (mild, moderate or high), primary study goal (pain study or not), data source (retrospective or not), and in a limited number of cases response/attrition rates. While correcting for these items, population characteristics correlating with pain prevalence rates were both proportion of patients with a depression and average time after injury (positive correlations). Between‐study heterogeneity may remain even after the identification/correction of above‐mentioned causes of heterogeneity.Pain after SCI does seem to relate to the duration of the injury and depression, yet major causes of bias in reported pain prevalence are found to be related to the primary study goal (pain study or not), choice of pain definition and the use of retrospective data.
Phototrophic growth of Arthrospira platensis in a respiration activity monitoring system for shake flasks (RAMOS®)
Authors: Socher Maria Lisa , Lenk Felix , Geipel Katja , Schott Carolin , Püschel Joachim , Haas Christiane , Grasse Christiane , Bley Thomas , Steingroewer Juliane
Published: May 2014

Optimizing illumination is essential for optimizing the growth of phototrophic cells and their production of desired metabolites and/or biomass. This requires appropriate modulation of light and other key inputs and continuous online monitoring of their metabolic activities. Powerful noninvasive systems for cultivating heterotrophic organisms include shake flasks in online monitoring units, but they are rarely used for phototrophs because they lack the appropriate illumination design and necessary illuminatory power. This study presents the design and characterization of a photosynthetic shake flask unit, illuminated from below by warm white light‐emitting diodes with variable light intensities up to 2300 μmol m−2 s−1. The photosynthetic unit was successfully used, in combination with online monitoring of oxygen production, to cultivate Arthrospira platensis. In phototrophic growth under continuous light and a 16 h light/8 h dark cycle (light intensity: 180 μmol m−2 s−1), the oxygen transfer rate and biomass‐related oxygen production were −1.5 mmol L−1 h−1 and 0.18 mmol O2 gx−1 h−1, respectively. The maximum specific growth rate was 0.058 h−1, during the exponential growth phase, after which the biomass concentration reached 0.75 g L−1.
A coalitional game scheme for cooperative interference management in cloud radio access networks
Authors: Sun Chengdan , Peng Mugen , Zhang Biling , Sun Yaohua , Li Yuan , Wang Chonggang
Published: May 2014

Cloud radio access networks (C‐RANs) are promising technological paradigms to improve capacity and extend coverage. However, the severe interference resulting from high density deployment of remote radio heads (RRHs) prevents to achieve high spectrum efficiency. How to mitigate the interference is a key challenging work. This paper investigates the cooperative interference management among RRHs in C‐RANs. By forming coalitions and performing non‐coherent joint transmission within a coalition, the intra‐coalition interference among RRHs can be successfully suppressed. Considering that RRHs are selfish and rational, in this paper, the cooperation of RRHs is formulated as a coalition formation game scheme, where the necessary conditions for an RRH to cooperate are derived. To find the solution for the proposed game, an enhanced concept of defection order is proposed, based on which a self‐optimal coalition formation algorithm is proposed. The performances of the proposed algorithm, in terms of convergence, complexity and fairness, are analysed as well. Simulation results show that our proposed algorithm yields significant improvements of system performance compared with both the non‐cooperative scheme and the conventional broadcasting‐based coalitional scheme.Copyright © 2014 John Wiley & Sons, Ltd.
Type‐I interferons suppress microglial production of the lymphoid chemokine, CXCL13
Authors: Esen Nilufer , Rainey‐Barger Emily K. , Huber Amanda K. , Blakely Pennelope K. , Irani David N.
Published: May 2014

Lymphoid chemokines are crucial for the development and maintenance of lymphoid organs, but their ectopic expression in non‐lymphoid tissues is implicated in both local response to infection and chronic organ‐specific autoimmunity. Production of one such chemokine, C‐X‐C motif ligand 13 (CXCL13), within the central nervous system (CNS) has been linked to the pathogenesis of multiple sclerosis (MS), although little is known about factors controlling its expression in different neural cell types and across a range of disease states. We provoked acute neuroinflammation in experimental animals without causing any associated demyelination using neuroadapted Sindbis virus (NSV) to better understand the sources and regulators of this chemokine in the CNS. We found that mice genetically deficient in the transcription factor, interferon (IFN) regulatory factor‐7 (IRF7), made significantly higher CXCL13 protein levels in the CNS compared with wild‐type (WT) controls. Microglia proved to be the main producer of CXCL13 in the brain during infection of both WT and IRF7−/− mice, and primary microglia cultured in vitro generated CXCL13 following stimulation with either virus particles or synthetic Toll‐like receptor (TLR) ligands. Microglia cultured from IRF7−/− mice selectively overproduced CXCL13, and manipulation of extracellular type‐I IFN levels demonstrated the existence of a negative feedback loop whereby type‐I IFN receptor signaling specifically suppressed microglial CXCL13 release. Since IFN‐β is used to treat patients with relapsing‐remitting MS and yet acts through unknown mechanisms, we speculate that suppressed lymphoid chemokine production by microglia could contribute to its therapeutic effects. GLIA 2014;62:1452–1462
Look at those two!: The precuneus role in unattended third‐person perspective of social interactions
Authors: Petrini Karin , Piwek Lukasz , Crabbe Frances , Pollick Frank E , Garrod Simon
Published: May 2014

Human beings often observe other people's social interactions without being a part of them. Whereas the implications of some brain regions (e.g. amygdala) have been extensively examined, the implication of the precuneus remains yet to be determined. Here we examined the implication of the precuneus in third‐person perspective of social interaction using functional magnetic resonance imaging (fMRI). Participants performed a socially irrelevant task while watching the biological motion of two agents acting in either typical (congruent to social conventions) or atypical (incongruent to social conventions) ways. When compared to typical displays, the atypical displays elicited greater activation in the central and posterior bilateral precuneus, and in frontoparietal and occipital regions. Whereas the right precuneus responded with greater activation also to upside down than upright displays, the left precuneus did not. Correlations and effective connectivity analysis added consistent evidence of an interhemispheric asymmetry between the right and left precuneus. These findings suggest that the precuneus reacts to violations of social expectations, and plays a crucial role in third‐person perspective of others' interaction even when the social context is unattended. Hum Brain Mapp 35:5190–5203, 2014. © 2014 Wiley Periodicals, Inc.
MicroRNA-331–3p promotes proliferation and metastasis of hepatocellular carcinoma by targeting PH domain and leucine-rich repeat protein phosphatase
Authors: Chang Rui-Min , Yang Hao , Fang Feng , Xu Jiang-Feng , Yang Lian-Yue
Published: May 2014

Hepatocellular carcinoma (HCC) is a highly invasive tumor with frequent intrahepatic or pulmonary metastasis, which is the main reason for high recurrence and poor survival of HCC after liver resection. However, the mechanisms for metastasis remain incompletely clear. Given that microRNAs (miRNAs) are implicated in HCC progression, we explored a potential role of miRNAs in metastasis by performing miRNA expression profiling in three subtypes of HCC with different metastatic potentials. We discovered miR-331–3p as one of most significantly overexpressed miRNAs and highly associated with metastasis of HCC. Increased expression of miR-331–3p was correlated with poor long-term survival of HCC. We provided both in vivo and in vitro evidence demonstrating that miR-331–3p promoted proliferation and metastasis of HCC cells. Using an integrated approach, we uncovered that PH domain and leucine-rich repeat protein phosphatase (PHLPP) was a novel target of miR-331–3p. Indeed, the miR-331–3p-mediated effects were antagonized by reexpression of PHLPP or mimicked by silencing of PHLPP. We further showed that miR-331–3p-mediated inhibition of PHLPP resulted in stimulation of protein kinase B (AKT) and subsequent epithelial mesenchymal transition (EMT). Finally, inhibition of miR-331–3p through a jetPEI-mediated delivery of anti-miR-331–3p vector resulted in marked inhibition of proliferation and metastasis of HCC in xenograft mice. Conclusion: miR-331–3p promotes proliferation and EMT-mediated metastasis of HCC through suppression of PHLPP-mediated dephosphorylation of AKT. Our work implicates miR-331–3p as a potential prognostic biomarker and a novel therapeutic target. (Hepatology 2014;60:1251–1263)
Synthesis of Dihydropyrans and Dihydrofurans via Radical Cyclization of Unsaturated Alcohols and 1,3‐Dicarbonyl Compounds
Authors: Aslan Hakan , Akpınar Deniz E. , Öktemer Atilla , Yakut Mehtap , Alagöz Oğuzhan
Published: May 2014

The oxidative cyclization reactions of 1,3‐dicarbonyl compounds 1a–1c and α,β‐unsaturated alcohols 2a–2f with Mn(OAc)3 were performed, leading to dihydrofurans. Treatment of 1a and 1b with 2‐methylbut‐3‐en‐2‐ol (2a) gave dihydrofurans 3aa and 3ba, and dihydropyrans 4aa and 4ba, as unexpected products. While the reaction of 2‐methylbut‐3‐yn‐2‐ol (2b) with acetylacetone (1b) yielded a bifuran, ethyl acetoacetate (1a) led to a mixture of furan, bifuran, and salicylate derivatives. Besides, surprisingly, styryl‐substituted dihydrofurans were obtained from the reactions of 1,3‐dicarbonyl compounds and (3E)‐2,4‐diphenylbut‐3‐en‐2‐ol. The reaction mechanisms were proposed for the formation of the different products, considering intermediates in these reaction mixtures.
Formal Total Synthesis of Stevastelins B and B3
Authors: Singh Yadav Jhillu , Sekhar Mandal Satadru , Srihari Pabbaraja
Published: May 2014

The formal total synthesis of stevastelins B and B3 (2 and 4, resp.) have been accomplished employing a highly enantiomerically controlled Lewis acid catalyzed non‐aldol approach to obtain the syn aldol product and temperature controlled hydroboration oxidation reaction to construct four consecutive stereogenic centers. The other key reactions include Sharpless asymmetric epoxidation, macrolactonization, and macrolactamization towards building the core skeleton 2 and 4.
New Alkaloids from Aconitum vaginatum
Authors: Li Juan , Chang Hang , Zhao Wenyu , Pi Huifang , Ruan Hanli , Zhang Peng
Published: May 2014

Two new amide alkaloids, vaginatunine A and B (1 and 2, resp.), and a new C18‐diterpenoid alkaloid vaginatunine C (3), together with four known alkaloids, were isolated from the tubers of Aconitum vaginatum. Their structures were determined by means of spectroscopic analyses and comparison of the data with those reported previously.
Highly Convergent One‐Pot Four‐Component Regioselective Synthesis of Spiro‐pyranopyrazoles and Oxa‐aza‐[3.3.3]propellanes
Authors: Alizadeh Abdolali , Bayat Fahimeh
Published: May 2014

A concise and efficient route for the synthesis of spiro‐pyranopyrazoles and oxa‐aza‐[3.3.3]propellanes by simple regioselective multicomponent reaction of ninhydrin, malononitrile, hydrazine derivatives, and β‐keto esters or dimethyl acetylenedicarboxylate was developed. This protocol provides an alternative method for combinatorial and parallel syntheses in drug discovery. The value of this method lies in its simplicity, regioselectivity, and good yields. The structures of 3 and 4 were corroborated spectroscopically (IR, 1H‐ and 13C‐NMR, and EI‐MS). A plausible mechanism for this type of reaction is proposed (Schemes 2 and 3).
Two New Iridoids from the Root and Rhizome of Valeriana jatamansiJones
Authors: Wang Su‐Juan , Qiu Xiao‐Qian , Zhu Jian‐Yong , Ma Xue‐Qing , Lin Bing , Zheng Cheng‐Jian , Qin Lu‐Ping
Published: May 2014

Two new iridoids, jatamanvaltrates P and Q (1 and 2, resp.), together with three known iridoids, rupesin B (3), chlorovaltrate (4), and valtrate (5), were isolated from the root and rhizome of Valeriana jatamansi Jones. The structures of the new compounds were elucidated by spectroscopic analyses, including 2D‐NMR techniques.
Synthesis and Anti‐HIV Activity of Triazolo‐Fused, Medium‐Sized Cyclic Nucleoside Analogs Prepared by an Intramolecular Huisgen 1,3‐Dipolar Cycloaddition
Authors: Sun Jingbo , Liu Rongwang , Fu Qiang , Zang Jian , Tao Qiangqiang , Wu Jinchang , Zhu Hui
Published: May 2014

Medium‐sized cyclic nucleosides containing a fused triazole ring were synthesized via intramolecular Huisgen 1,3‐dipolar cycloadditon reaction. 2′,3′‐seco‐Uridine was employed as the key intermediate for the introduction of azido and alkynyl moieties in the defined positions of the reaction precursors. The cycloaddition reactions were achieved in high yields by heating the precursor in refluxing toluene. The uracil base in these target compounds was successfully transformed to the corresponding cytosine. The synthesized compounds were evaluated in a MAGI assay for their anti‐HIV activities, and in a H9 T lymphocytes assay for their cell toxicities.
Slipping up: Partial substrate degradation by ATP‐dependent proteases
Authors: Nassif Nicholas D. , Cambray Samantha E. , Kraut Daniel A.
Published: May 2014

ATP‐dependent proteases are present in all organisms, where they are responsible for much of intracellular protein degradation. Most proteins are processively unfolded and degraded into small peptides; however, in a few so‐called slippery substrates, the protease stalls at a folded domain and releases a large protein fragment. In this review, we describe the properties of physiological slippery substrates that are processed in this manner by ATP‐dependent proteases and the recent advances that have been made in understanding the mechanism underlying their partial degradation. © 2014 IUBMB Life, 66(5):309–317, 2014
Teaching braille line tracking using stimulus fading
Authors: Scheithauer Mindy C. , Tiger Jeffrey H.
Published: May 2014

Line tracking is a prerequisite skill for braille literacy that involves moving one's finger horizontally across a line of braille text and identifying when a line ends so the reader may reset his or her finger on the subsequent line. Current procedures for teaching line tracking are incomplete, because they focus on tracking lines with only small gaps between characters. The current study extended previous line‐tracking instruction using stimulus fading to teach tracking across larger gaps. After instruction, all participants showed improvement in line tracking, and 2 of 3 participants met mastery criteria for tracking across extended spaces.
Extracorporeal photopheresis: Technique, established and novel indications
Authors: Marques Marisa B. , Adamski Jill
Published: May 2014

Extracorporeal photopheresis (ECP) has had a major impact in the treatment of various conditions in the past 25 years. Although it was initially developed for the treatment of patients with resistant cutaneous T cell lymphoma (CTCL), this therapy was later used to treat recipients of solid organs and stem cell transplants with rejection or graft‐versus‐host disease (GVHD), respectively. A significant number of patients with CTCL can achieve long term remission with ECP therapy. Those patients with heart or lung transplants may experience fewer or shorter rejection episodes following ECP. Furthermore, patients that respond to ECP can generally reduce the dose of immunosuppression medication, thus minimizing the morbidity caused by drugs such as corticosteroids and calcineurin inhibitors. While the exact mechanism of action of ECP is not well‐understood, evidence suggests that reinfusion of the patient's apoptotic white blood cells, the ultimate product of ECP, promotes immunomodulatory events that are beneficial in patients with CTCL, transplant rejection, GVHD, and possibly other inflammatory conditions. J. Clin. Apheresis 29:228–234, 2014. © 2014 Wiley Periodicals, Inc.
A NEW MEASURE FOR ASSESSING YOUTH PROGRAM PARTICIPATION
Authors: Tiffany Jennifer Sarah , Exner‐Cortens Deinera , Eckenrode John
Published: May 2014

Participation in after‐school programs is an important lever to improve adolescents’ health and well‐being; however, well‐defined measurement of the quality of participation in these programs is limited. The present study validated a newly designed measure of participation in a sample of urban youth enrolled in community‐based after‐school programs. Exploratory and confirmatory factor analyses were used to test the structure of the 20‐item Tiffany‐Eckenrode Program Participation Scale (TEPPS). Results suggest that the scale comprises four subscales (Personal Development, Voice/Influence, Safety/Support and Community Engagement). The TEPPS was also correlated with several commonly used measures of program participation. Findings from this article provide support for the use of the newly designed scale as a valid and reliable measure of quality program participation by youth.
Optimization of photocatalytic decolorization of C.I. Basic Blue 41 in semi‐pilot scale prototype solar photoreactor
Authors: Bouchareb Mohammed Kheir‐eddine , Bouhelassa Mohamed , Berkani Mohammed
Published: May 2014

BACKGROUND

The photocatalytic decolorization of C.I. Basic blue (BB41) in aqueous catalyst suspensions of titanium dioxide (TiO2), Degussa P25, was carried out in a semi‐pilot scale prototype solar photoreactor equipped with compound parabolic collectors (CPCs). The experiments on the solar reactor were performed with and without collectors. Response surface methodology (RSM) was applied to assess individual and interactive effects of the four main independent parameters (initial dye concentration, TiO2concentration, flow rate and initial pH) on the decolorization efficiency, the central composite design (CCD) was used for optimization of UV/TiO2 process.

RESULTS

The presence of the collectors has increased the rate of decolorization of 50% for an initial dye concentration of 40 mg L−1 and after 80 kJ L−1 of visible energy accumulated. Predicted values of decolorization efficiency according to RSM were in close agreement with the experimental values (R2 = 0.9626, Adj‐R2 = 0.9252). Optimization results showed that maximum decolorization efficiency was achieved at the optimum conditions catalyst concentration 0.577 g L−1, initial dye concentration 17.933 mg L−1, flow rate 1446.8 L h−1 and initial pH 4.6 for 60 kJ L−1 of VIS energy accumulated.

CONCLUSION

The photocatalytic decolorization of a textile dye, C.I. Basic Blue 41, in a tubular solar prototype photoreactor was optimized. Response surface methodology based on the central composite design has been shown to be a powerful tool in the development of any photocatalytic process due to its impact on the economy and practicability of the process. © 2014 Society of Chemical Industry
Comparison of inflammation‐based prognostic scores as predictors of tumor recurrence in patients with hepatocellular carcinoma after curative resection
Authors: Yamamura Kazuo , Sugimoto Hiroyuki , Kanda Mitsuro , Yamada Suguru , Nomoto Shuji , Nakayama Goro , Fujii Tsutomu , Koike Masahiko , Fujiwara Michitaka , Kodera Yasuhiro
Published: May 2014

Background

Various inflammation‐based prognostic scores, including the Glasgow prognostic score (GPS), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), prognostic index (PI), and prognostic nutritional index (PNI), have been associated with survival in patients with several types of cancer. This study compared the ability of these scores to predict recurrence‐free survival (RFS) in patients with hepatocellular carcinoma (HCC) after curative hepatectomy.

Methods

Data were collected prospectively from 113 patients who underwent curative resection for HCC from January 2003 to December 2012. Clinicopathological variables including preoperative inflammation‐based prognostic scores were analyzed. Univariate and multivariate analyses were performed to identify factors predictive of RFS.

Results

Univariate analysis showed that NLR (P < 0.0001) and PI (P = 0.0194) were significantly associated with RFS. Multivariate analysis showed that NLR (hazard ratio [HR]; 2.58, P = 0.0020), tumor differentiation (HR; 9.55, P < 0.0001), serosal invasion (HR; 2.24, P = 0.0112), and vascular invasion (HR; 2.18, P = 0.0106) were independently correlated with RFS.

Conclusions

Preoperative NLR is an independent predictor of RFS in patients with HCC after curative hepatectomy, and is superior to the other inflammation‐based prognostic scores.
Role of vasopressin and its antagonism in stroke related edema
Authors: Ameli Pouya A. , Ameli Neema J. , Gubernick David M. , Ansari Saeed , Mohan Shekher , Satriotomo Irawan , Buckley Alexis K. , Maxwell Christopher W. , Nayak Vignesh H. , Shushrutha Hedna Vishnumurthy
Published: May 2014

Although many approaches have been tried in the attempt to reduce the devastating impact of stroke, tissue plasminogen activator for thromboembolic stroke is the only proved, effective acute stroke treatment to date. Vasopressin, an acute‐phase reactant, is released after brain injury and is partially responsible for the subsequent inflammatory response via activation of divergent pathways. Recently there has been increasing interest in vasopressin because it is implicated in inflammation, cerebral edema, increased intracerebral pressure, and cerebral ion and neurotransmitter dysfunctions after cerebral ischemia. Additionally, copeptin, a byproduct of vasopressin production, may serve as a promising independent marker of tissue damage and prognosis after stroke, thereby corroborating the role of vasopressin in acute brain injury. Thus, vasopressin antagonists have a potential role in early stroke intervention, an effect thought to be mediated via interactions with aquaporin receptors, specifically aquaporin‐4. Despite some ambiguity, vasopressin V1a receptor antagonism has been consistently associated with attenuated secondary brain injury and edema in experimental stroke models. The role of the vasopressin V2 receptor remains unclear, but perhaps it is involved in a positive feedback loop for vasopressin expression. Despite the encouraging initial findings we report here, future research is required to characterize further the utility of vasopressin antagonists in treatment of stroke. © 2014 Wiley Periodicals, Inc.
Cortical ablation induces time‐dependent changes in rat pituitary somatotrophs and upregulates growth hormone receptor expression in the injured cortex
Authors: Lavrnja Irena , Ajdzanovic Vladimir , Trifunovic Svetlana , Savic Danijela , Milosevic Verica , Stojiljkovic Mirjana , Pekovic Sanja
Published: May 2014

The pituitary appears to be vulnerable to brain trauma, and its dysfunction is a common feature after traumatic brain injury. The role of pituitary growth hormone (GH) in brain repair after injury has been envisaged, but more studies must be performed to understand completely the importance of GH in these processes. Because some of the neuroprotective effects of GH are mediated directly through the GH receptor (GHR), we examined GHR expression in the rat cerebral cortex after sensorimotor cortex ablation. RT‐PCR, immunohistochemistry, and double immunofluorescence had been performed to analyze the correlation between GHR expression in the injured cortex and activity of GH cells in the pituitary. Our results showed that the volume of GH‐immunopositive cells was reduced at days 2 and 7 postsurgery (dps), and volume density of GH cells was significantly decreased at 14 dps, all compared with appropriate sham controls. At 30 dps all investigated parameters had returned to control level. In the injured cortex, GHR expression was transiently upregulated. Increased GHR immunoreactivity was observed in reactive astrocytes at 7 and particularly at 14 dps. In neuronal cells, an increase of GHR immunoreactivity was seen in neuronal cell bodies and well‐defined primary dendrites at 14 and especially at 30 dps. The results presented here suggest that, during recovery from brain injury, changes in activity of pituitary GH cells result in upregulation of GHR that may have a role in neuronal arborization and glial proliferation in the injured cortex. © 2014 Wiley Periodicals, Inc.
Cocoa content influences chocolate molecular profile investigated by MALDI‐TOF mass spectrometry
Authors: Bonatto Cínthia C , Silva Luciano P
Published: May 2014

BACKGROUND

Chocolate authentication is a key aspect of quality control and safety. Matrix‐assisted laser desorption ionization time‐of flight (MALDI‐TOF) mass spectrometry (MS) has been demonstrated to be useful for molecular profiling of cells, tissues, and even food. The present study evaluated if MALDI‐TOF MS analysis on low molecular mass profile may classify chocolate samples according to the cocoa content.

RESULTS

The molecular profiles of seven processed commercial chocolate samples were compared by using MALDI‐TOF MS. Some ions detected exclusively in chocolate samples corresponded to the metabolites of cocoa or other constituents. This method showed the presence of three distinct clusters according to confectionery and sensorial features of the chocolates and was used to establish a mass spectra database. Also, novel chocolate samples were evaluated in order to check the validity of the method and to challenge the database created with the mass spectra of the primary samples. Thus, the method was shown to be reliable for clustering unknown samples into the main chocolate categories.

CONCLUSION

Simple sample preparation of the MALDI‐TOF MS approach described will allow the surveillance and monitoring of constituents during the molecular profiling of chocolates. © 2014 Society of Chemical Industry
Y‐ and H‐Shaped Amphiphilic PEG–PCL Block Copolymers Synthesized Combining Ring‐Opening Polymerization and Click Chemistry: Characterization and Self‐Assembly Behavior
Authors: Tirino Pasquale , Conte Claudia , Ordegno Monica , Palumbo Rosario , Ungaro Francesca , Quaglia Fabiana , Maglio Giovanni
Published: May 2014

The aim of this work is to obtain poly(ethylene glycol) (PEG) (hydrophilic)–poly(ε‐caprolactone) (PCL) (hydrophobic) block copolymers with different architectures to point out the influence of this parameter on the water self‐assembly behavior. The key role in the copolymer synthesis is played by a click chemistry strategy based on Huisgen cycloaddition, between the alkyne and azide terminal groups of different polymeric segments. The obtained copolymers are characterized by NMR, Fourier transform IR (FTIR) spectroscopy, differential scanning calorimetry (DSC), wide‐angle X‐ray diffraction (WAXD), and size‐exclusion chromatography (SEC) techniques. In an aqueous environment, the hydrophilic and hydrophobic blocks of the amphiphilic copolymers form the corona and the core of the nanoaggregates, respectively, giving different morphologies as a function of the copolymer architecture. Furthermore, dynamic light scattering (DLS), transmission electron microscopy (TEM), and zeta potential measurements reveal promising features as nanocarriers of lipophilic molecules.

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Recent Progress on C‐4‐Modified Podophyllotoxin Analogs as Potent Antitumor Agents
Authors: Liu Ying‐Qian , Tian Jing , Qian Keduo , Zhao Xiao‐Bo , Morris‐Natschke Susan L. , Yang Liu , Nan Xiang , Tian Xuan , Lee Kuo‐Hsiung
Published: May 2014

Podophyllotoxin (PPT), as well as its congeners and derivatives, exhibits pronounced biological activities, especially antineoplastic effects. Its strong inhibitory effect on tumor cell growth led to the development of three of the most highly prescribed anticancer drugs in the world, etoposide, teniposide, and the water‐soluble prodrug etoposide phosphate. Their clinical success as well as intriguing mechanism of action stimulated great interest in further modification of PPT for better antitumor activity. The C‐4 position has been a major target for structural derivatization aimed at either producing more potent compounds or overcoming drug resistance. Accordingly, numerous PPT derivatives have been prepared via hemisynthesis and important structure–activity relationship (SAR) correlations have been identified. Several resulting compounds, including GL‐331, TOP‐53, and NK611, reached clinical trials. Some excellent reviews on the distribution, sources, applications, synthesis, and SAR of PPT have been published. This review focuses on a second generation of new etoposide‐related drugs and provides detailed coverage of the current status and recent development of C‐4‐modified PPT analogs as anticancer clinical trial candidates.
Quantifying iron‐oxide nanoparticles at high concentration based on longitudinal relaxation using a three‐dimensional SWIFT look‐locker sequence
Authors: Zhang Jinjin , Chamberlain Ryan , Etheridge Michael , Idiyatullin Djaudat , Corum Curtis , Bischof John , Garwood Michael
Published: May 2014

Purpose

Iron‐oxide nanoparticles (IONPs) have proven utility as contrast agents in many MRI applications. Previous quantitative IONP mapping has been performed using mainly T2* mapping methods. However, in applications requiring high IONP concentrations, such as magnetic nanoparticles based thermal therapies, conventional pulse sequences are unable to map T2* because the signal decays too rapidly. In this article, sweep imaging with Fourier transformation (SWIFT) sequence is combined with the Look‐Locker method to map T1 of IONPs in high concentrations.

Methods

T1 values of agar containing IONPs in different concentrations were measured with the SWIFT Look‐Locker method and with inversion recovery spectroscopy. Precisions of Look‐Locker and variable flip angle (VFA) methods were compared in simulations.

Results

The measured R1 (=1/T1) has a linear relationship with IONP concentration up to 53.6 mM of Fe. This concentration exceeds concentrations measured in previous work by almost an order of magnitude. Simulations show SWIFT Look‐Locker method is also much less sensitive to B1 inhomogeneity than the VFA method.

Conclusion

SWIFT Look‐Locker can accurately measure T1 of IONP concentrations ≤53.6 mM. By mapping T1 as a function of IONP concentration, IONP distribution maps might be used in the future to plan effective magnetic nanoparticle hyperthermia therapy. Magn Reson Med 71:1982–1988, 2014. © 2014 Wiley Periodicals, Inc.
Structure‐energy‐based predictions and network modelling of RASopathy and cancer missense mutations
Authors: Kiel Christina , Serrano Luis
Published: May 2014

The Ras/MAPK syndromes (‘RASopathies’) are a class of developmental disorders caused by germline mutations in 15 genes encoding proteins of the Ras/mitogen‐activated protein kinase (MAPK) pathway frequently involved in cancer. Little is known about the molecular mechanisms underlying the differences in mutations of the same protein causing either cancer or RASopathies. Here, we shed light on 956 RASopathy and cancer missense mutations by combining protein network data with mutational analyses based on 3D structures. Using the protein design algorithm FoldX, we predict that most of the missense mutations with destabilising energies are in structural regions that control the activation of proteins, and only a few are predicted to compromise protein folding. We find a trend that energy changes are higher for cancer compared to RASopathy mutations. Through network modelling, we show that partly compensatory mutations in RASopathies result in only minor downstream pathway deregulation. In summary, we suggest that quantitative rather than qualitative network differences determine the phenotypic outcome of RASopathy compared to cancer mutations.
Prebiotic metabolic networks?
Authors: Luisi Pier Luigi
Published: May 2014

A prebiotic origin of metabolism has been proposed as one of several scenarios for the origin of life. In their recent work, Ralser and colleagues (Keller et al, ) observe an enzyme‐free, metabolism‐like reaction network under conditions reproducing a possible prebiotic environment.
What patients are reading about noninvasive prenatal testing: an evaluation of Internet content and implications for patient‐centered care
Authors: Mercer M. B. , Agatisa P. K. , Farrell R. M.
Published: May 2014

Objective

Patients' use of the Internet as a source of health information is increasing. The objective of this study was to describe and evaluate Internet‐based information about noninvasive prenatal testing (NIPT), an important new genetic test currently available to high‐risk women in early pregnancy.

Methods

Websites were sampled using leading search engines to mirror Internet‐based search patterns of individuals seeking information about NIPT. Content analysis was conducted to assess website reading level, quality, and content.

Results

Basic information about NIPT use as a screening test was accurately described. Overall, sampled websites lacked balance and comprehensive information about NIPT and the complexity of decision making involved in electing for its use. All websites were written at reading levels higher than currently recommended levels for public health information.

Conclusion

While online resources should be used with reservation, they can be an important tool to support effective communication and patient‐centered care. Online information can help both health care providers and pregnant patients who face a growing number of fetal genetic testing options. © 2014 John Wiley & Sons, Ltd.
Absolute quantification of the Kdp subunits of Escherichia coli by multiple reaction monitoring
Authors: Surmann Kristin , Laermann Vera , Zimmann Petra , Altendorf Karlheinz , Hammer Elke
Published: May 2014

The sensor kinase/response regulator system KdpD/KdpE of Escherichia coli regulates the expression of the kdpFABC operon, encoding the high‐affinity KdpFABC potassium (K+)‐transport complex. Additionally, it has been suggested that the kdpDE operon itself is subjected to autoregulation by its gene products KdpD and KdpE. However, since kdpFABC and kdpDE expression has mainly been studied on the transcriptional level, accurate information on absolute amounts and the stoichiometric subunit composition of KdpFABC and KdpD/KdpE under K+‐limiting and K+‐nonlimiting growth conditions are lacking. In this study, we used highly sensitive mass spectrometric methods to quantify the amount of subunits of the Kdp(F)ABC complex and KdpD/KdpE. Data‐dependent shotgun MS was used to assess protein coverage and accessible peptides. Absolute amounts of Kdp(F)ABC and KdpD/KdpE were quantified by targeted MRM analysis in the presence of corresponding heavy labeled standard peptides. Baseline synthesis of Kdp(F)ABC and KdpD/KdpE was found to be in the attomolar range under K+‐nonlimiting conditions. Under K+‐limitation, synthesis of Kdp(F)ABC (KdpA:KdpB:KdpC ratio of 1:1:1) was amplified more than 100‐fold, whereas only a tenfold amplification of KdpD/KdpE (KdpD:KdpE ratio of 1:4) was observed. The results obtained provide a solid basis for follow‐up studies on the dynamic regulation of the Kdp system.