bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and properties of new water‐soluble copolymers based on methyl acrylic acid sucrose ester and methyl acrylic acid
Authors: Chen Yan , Liu Jin , Li Zhen
Published: April 2016

The new series of copolymers were obtained based on free radical solution copolymerization by mixing self‐made methyl acrylic acid sucrose ester (MASE) and methyl acrylic acid (MAA) with different ratios. Copolymerization behavior and properties of the new copolymers was investigated with the reaction time, temperature, monomer ratios and characterized by Fourier transform infrared spectra (FT‐IR), carbon nuclear magnetic resonance (13C NMR), and intrinsic viscosity. The results indicated that sucrose was successfully grafted onto poly (methyl acrylic acid). Further, it was demonstrated that low temperature benefited the esterification of MASE. Importantly, the copolymers were founded to have good compatibility with polymethyl methacrylate (PMMA), polytetrafluoroethylene (PTFE), and polyethylene (PE). © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci.2016,133, 43627.
INHIBITION OF FATTY ACID DESATURASES IN Drosophila melanogaster LARVAE BLOCKS FEEDING AND DEVELOPMENTAL PROGRESSION
Authors: Wang Yiwen , da Cruz Tina Correia , Pulfemuller Alicia , Grégoire Stéphane , Ferveur Jean‐François , Moussian Bernard
Published: April 2016

Fatty acid desaturases are metabolic setscrews. To study their systemic impact on growth in Drosophila melanogaster, we inhibited fatty acid desaturases using the inhibitor CAY10566. As expected, the amount of desaturated lipids is reduced in larvae fed with CAY10566. These animals cease feeding soon after hatching, and their growth is strongly attenuated. A starvation program is not launched, but the expression of distinct metabolic genes is activated, possibly to mobilize storage material. Without attaining the normal size, inhibitor‐fed larvae molt to the next stage indicating that the steroid hormone ecdysone triggers molting correctly. Nevertheless, after molting, expression of ecdysone‐dependent regulators is not induced. While control larvae molt a second time, these larvae fail to do so and die after few days of straying. These effects are similar to those observed in experiments using larvae deficient for the fatty acid desaturase1 gene. Based on these data, we propose that the ratio of saturated to unsaturated fatty acids adjusts a sensor system that directs feeding behavior. We also hypothesize that loss of fatty acid desaturase activity leads to a block of the genetic program of development progression indirectly by switching on a metabolic compensation program.
Dissecting the voice: Health professions students' perceptions of instructor age and gender in an online environment and the impact on evaluations for faculty
Authors: Doubleday Alison F. , Lee Lisa M.J.
Published: April 2016

Gender and age bias is well‐documented in academia with many studies demonstrating bias in students' evaluations of instructors. Failure of an instructor to meet gender or age‐based expectations can translate to lower scores or negative comments on evaluations. While there is some evidence of bias in students' evaluations of online instructors, current studies have not fully examined the relationship between bias and instructor vocal characteristics. First‐year dental students at two institutions were randomly assigned one of four videos on spinal cord anatomy to view. Videos contained identical content but were narrated by individuals of different gender and age (younger man, younger woman, older man, older woman). Students completed a content‐based prequiz, watched the video, completed a postquiz, and answered a questionnaire evaluating the video and instructor. Students at Institution A rated the younger man and younger woman highest for nearly every evaluation category. At Institution B students rated the older man and younger woman highest. Results reveal that the older woman's voice received the lowest rankings for nearly every question in both samples. This report confirms the presence of gender and age bias in student evaluations of instructors in an online environment and demonstrates that bias may surface in response to vocal characteristics. Bias may impact older women more significantly than other groups. Differences in results from Institution A and Institution B suggest that factors affecting student perceptions of instructors, and the roles that gender and age bias may play in student evaluations, are complex and may be contextual. Anat Sci Educ 9: 537–544. © 2016 American Association of Anatomists.
Effect of Spacer Connecting the Secondary Electron Donor Phenothiazine in Subphthalocyanine–Fullerene Conjugates in Promoting Electron Transfer Followed by Hole Shift Process
Authors: KC Chandra B. , Lim Gary N. , D'Souza Francis
Published: April 2016

Sequential electron/hole transfer between energetically well‐positioned entities of photosynthetic reaction center models is one of the commonly employed mechanisms to generate long‐lived charge‐separated states. A wealth of information, applicable towards light energy harvesting and building optoelectronic devices, has been acquired from such studies. In the present study, we report on the effect of spacer (direct or via phenoxy linkage) connecting the hole shifting agent, phenothiazine (PTZ), on photoinduced charge stabilization in subphthalocyanine–fullerene donor–acceptor conjugates. In these conjugates, the subphthalocyanine (SubPc) and fullerene (C60) served as primary electron donor and acceptor, respectively, while the phenothiazine entities act as hole shifting agents. The newly synthesized compounds were characterized by optical absorption and emission, computational, and electrochemical methods. The redox potentials measured using differential pulse voltammetry were used to estimate free‐energy changes for charge separation, hole migration, and charge recombination processes. Using femto‐ and nanosecond transient absorption techniques, evidence for charge separation, and kinetics of charge separation and recombination were obtained in polar benzonitrile and nonpolar toluene solvents. In the conjugate where the phenothiazine entities are directly linked to SubPc, evidence for sequential electron transfer followed by hole shift leading to long‐lived charge separated state was weak, primarily due to the delocalization of HOMO on both SubPc and PTZ entities. However, in case of the conjugate where the PTZ and SubPc are linked via phenoxy spacers, sequential electron transfer/hole shift was observed leading to the formation of long‐lived charge‐separated states. The present study brings out the importance of the spacer group connecting the hole shifting agent in model donor–acceptor conjugates to generate long‐lived charge‐separated states.
Ligand‐Free, Cu‐ and Fe‐Catalyzed Selective Ring‐Opening Arylations of Benzoxazoles with Aryl Iodides
Authors: He Yue , Mao Jincheng , Rong Guangwei , Yan Hong , Zhang Guoqi
Published: April 2016

Cu‐ or Fe‐based catalyst systems have been reported to selectively catalyze the N,N‐diarylation or N‐monoarylation of benzoxazoles ring‐opening with aryl iodides in the absence of additional added ligand in polyethylene glycol under an inert atmosphere. Two types of coupling products (triphenylamines and diphenylamines) have been examined and the reaction routes can be simply controlled by changing the metal salts (Cu or Fe) as catalyst. A range of substrates have been investigated for the diverse reactions, and the corresponding arylation products were achieved in good to high yields. This selective, low‐cost, and environmentally friendly protocol displays great potential for replacing existing methodologies as well as extending the synthetic applications of benzoxazoles.
Trajectory Tracking Control of an Underactuated Underwater Vehicle Redundant Manipulator System
Authors: Korkmaz Ozan , Ider S. Kemal , Ozgoren M. Kemal
Published: April 2016

The purpose of this study is to control the position of an underactuated underwater vehicle manipulator system (U‐UVMS). It is possible to control the end‐effector using a regular 6‐DOF manipulator despite the undesired displacements of the underactuated vehicle within a certain range. However, in this study an 8‐DOF redundant manipulator is used in order to increase the positioning accuracy of the end‐effector. The redundancy is resolved according to the criterion of minimal vehicle and joint motions. The underactuated underwater vehicle redundant manipulator system is modeled including the hydrodynamic forces for the manipulator in addition to those for the autonomous underwater vehicle (AUV). The shadowing effects of the bodies on each other are also taken into account when computing the hydrodynamic forces. The Newton‐Euler formulation is used to derive the system equations of motion including the thruster dynamics. In order to establish the end‐effector trajectory tracking control of the system, an inverse dynamics control law is formulated. The effectiveness of the control law even in the presence of parameter uncertainties and disturbing ocean currents is illustrated by simulations.
Embedded MPC Controller Based on Interior‐Point Method with Convergence Depth Control
Authors: Ding Yi , Xu Zuhua , Zhao Jun , Wang Kexin , Shao Zhijiang
Published: April 2016

To allow the implementation of model predictive control on the chip, we first propose a primal–dual interior point method with convergence depth control to solve the quadratic programming problem of model predictive control. Compared with algorithms based on traditional termination criterion, the proposed method can significantly reduce the computation cost while obtaining an approximate solution of the quadratic programming problem with acceptable optimality and precision. Thereafter, an embedded model predictive controller based on the quadratic programming solver is designed and implemented on a digital signal processor chip and a prototype system is built on a TMDSEVM6678LE digital signal processor chip. The controller is verified on two models by using the hardware in loop frame to mimic real applications. The comparison shows that the whole design is competitive in real‐time applications. The typical computation time for quadratic programming problems with 5 decision variables and 110 constraints can be reduced to less than 2 ms on an embedded platform.
Hierarchical Control of Linear Systems from the Abstraction Feedback Gain
Authors: Kaihong Yang , Haibo Ji
Published: April 2016

In this paper, the problem of hierarchical control for a class of linear systems is addressed. Given a large‐scale linear system, we obtain a stabilizing feedback gain for it from that of an abstract system. And then, we employ this feedback gain to design a new interface between the original system and the abstraction. Furthermore, the synthesis of the new interface can be allowed by a new simulation function characterized by a low‐order matrix associated to the abstraction. Finally, an example is given to illustrate the proposed approach.
Identifying children with autism spectrum disorder based on their face processing abnormality: A machine learning framework
Authors: Liu Wenbo , Li Ming , Yi Li
Published: April 2016

The atypical face scanning patterns in individuals with Autism Spectrum Disorder (ASD) has been repeatedly discovered by previous research. The present study examined whether their face scanning patterns could be potentially useful to identify children with ASD by adopting the machine learning algorithm for the classification purpose. Particularly, we applied the machine learning method to analyze an eye movement dataset from a face recognition task [Yi et al., 2016], to classify children with and without ASD. We evaluated the performance of our model in terms of its accuracy, sensitivity, and specificity of classifying ASD. Results indicated promising evidence for applying the machine learning algorithm based on the face scanning patterns to identify children with ASD, with a maximum classification accuracy of 88.51%. Nevertheless, our study is still preliminary with some constraints that may apply in the clinical practice. Future research should shed light on further valuation of our method and contribute to the development of a multitask and multimodel approach to aid the process of early detection and diagnosis of ASD. Autism Res 2016, 9: 888–898. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Targeted DNA delivery to cancer cells using a biotinylated chitosan carrier
Authors: Darvishi Mohammad H. , Nomani Alireza , Hashemzadeh Hadi , Amini Mohsen , Shokrgozar Mohammad A. , Dinarvand Rassoul
Published: April 2016

A novel biotinylated chitosan‐graft‐polyethyleneimine (Bio‐Chi‐g‐PEI) copolymer was synthesized and evaluated as a nonviral gene delivery carrier for improvement of the transfection efficiency, endosomal escape, and targeted gene delivery of a plasmid encoding green fluorescent protein N1 (pEGFP‐N1) into two different biotin‐overexpressing cell lines including HeLa and OVCAR‐3 cells. The structure of the obtained copolymers was confirmed by 1H nuclear magnetic resonance (1H NMR) and Fourier transform infrared spectroscopy. Physicochemical properties of the Bio‐Chi‐g‐PEI/plasmid DNA (pDNA) complexes such as complex stability, size, zeta potential, and their morphology were investigated at various weight ratios of copolymer to pDNA. Bio‐Chi‐g‐PEI copolymers could effectively condense pDNA into small particles with average diameters less than 164 nm and the zeta potential of +34.8 mV at the N/P ratio of 40/1. As revealed by flow cytometry, Bio‐Chi‐g‐PEI/pDNA complexes had lower cytotoxicity than that of PEI 25 kDa/pDNA complexes in both cell lines. In vitro experiments revealed that the Bio‐Chi‐gPEI/pDNA complexes not only had much lower cytotoxicity, but also displayed higher transfection efficiency than that of PEI 25kDa/pDNA complexes. High percentage of cancer cells was successfully transfected by Bio‐Chi‐g‐PEI/pDNA and properly expressed GFP protein. This study indicates that this copolymer complex can be a promising gene delivery carrier.
An Expectancy Theory Approach to Group Coordination: Expertise, Task Features, and Member Behavior
Authors: Baumann Michael R. , Bonner Bryan L.
Published: April 2016

Working in a group requires coordination. The current paper examines coordination in terms of member‐level behavioral choices. Extending expectancy theory to a collaborative group setting, we interpret past findings on expertise and hypothesize that component features (specifically their difficulty and worth relative to each other) impact member behavior and hence coordination both directly and by moderating the role of expertise. Findings were largely as predicted, suggesting that an expectancy theory perspective may be a useful tool for the study and understanding of coordination. An exploratory examination of recordings of group interaction suggested that although most of our groups discussed coordination strategies, the strategies discussed did not generally map to the behavioral choices observed. Implications for coordination in general and transactive memory specifically are discussed. Copyright © 2016 John Wiley & Sons, Ltd.
The Selection of Freebies and the Preference for Freebie Promotions—A Perspective on Item Characteristics
Authors: Liu Hsin‐Hsien , Chou Hsuan‐Yi
Published: April 2016

Research on consumer decision making has mainly focused on individual products; however, many products are purchased with other items as part of a promotional package. This paper explores how the characteristics (hedonic versus utilitarian) of the items in freebie promotional packages (e.g., buy one item and get a different item for free) influence consumers' preference for the promotional package. Additionally, the authors examine how the characteristics of the focal item influence consumers' choice of either a hedonic or a utilitarian freebie item. Five experiments, rooted in the concepts of consumer avoidance of overloading negative emotions and motivation to seek hedonic pleasure, show that a package with one utilitarian and one hedonic item generates higher purchase intentions and willingness to pay than a package with either two hedonic or two utilitarian items. Furthermore, consumers who purchase a hedonic (utilitarian) focal item are more likely to choose a utilitarian (hedonic) freebie. These effects exist not only in hypothetical scenarios but also in an incentive‐compatible design. Moreover, the impact of the focal item characteristics on consumer choice of freebie is moderated by acquisition format and time separation. The authors also explore the internal mechanism influencing consumers' freebie choices. The findings have significant implications for both theory and practice. Copyright © 2016 John Wiley & Sons, Ltd.
A Probability Analysis of Historical Pregnancy and Fetal Data from Dutch Belted and New Zealand White Rabbit Strains from Embryo–Fetal Development Studies
Authors: Posobiec Lorraine M. , Cox Estella M. , Solomon Howard M. , Lewis Elise M. , Wang Kai‐fen , Stanislaus Dinesh
Published: April 2016

Embryo‐fetal development (EFD) studies, typically in pregnant rats and rabbits, are conducted prior to enrolling females of reproductive age in clinical trials. Common rabbit strains used are the New Zealand White (NZW) and Dutch Belted (DB). As fetal abnormalities can occur in all groups, including controls, Historical Control Data (HCD) is compiled using data from control groups of EFD studies, and is used along with each study's concurrent control group to help determine whether fetal abnormalities are caused by the test article or are part of background incidences. A probability analysis was conducted on 2014 HCD collected at Charles River Inc., Horsham PA on Covance NZW, Covance DB, and Charles River (CR) NZW rabbits. The analysis was designed to determine the probability of 2 or 3 out of a group of 22 does aborting their litter or of having a fetal abnormality by chance. Results demonstrate that pregnancy parameters and fetal observations differ not only between strains, but between sources of rabbits of the same strain. As a result the probability of these observations occurring by chance in two or three litters was drastically different. Although no one single strain is perfect, this analysis highlights the need to appreciate the inherent differences in pregnancy and fetal abnormalities between strains, and points out that an apparent isolated increased incidence of an observation in one strain will not necessarily be test‐article related in another strain. A robust HCD is critical for interpretation of EFD rabbit studies, regardless of the rabbit strain used
Invited review: Architectures and mechanisms of ATP binding cassette proteins
Authors: Hopfner Karl‐Peter
Published: April 2016

ATP binding cassette (ABC) ATPases form chemo‐mechanical engines and switches that function in a broad range of biological processes. Most prominently, a very large family of integral membrane NTPases—ABC transporters—catalyzes the import or export of a diverse molecules across membranes. ABC proteins are also important components of the chromosome segregation, recombination, and DNA repair machineries and regulate or catalyze critical steps of ribosomal protein synthesis. Recent structural and mechanistic studies draw interesting architectural and mechanistic parallels between diverse ABC proteins. Here, I review this state of our understanding how NTP‐dependent conformational changes of ABC proteins drive diverse biological processes. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 492–504, 2016.
Identification of non‐random sequence properties in groups of signature peptides obtained in random sequence peptide microarray experiments
Authors: Kuznetsov Igor B.
Published: April 2016

Immunosignaturing is an emerging experimental technique that uses random sequence peptide microarrays to detect antibodies produced by the immune system in response to a particular disease. Two important questions regarding immunosignaturing are “Do microarray peptides that exhibit a strong affinity to a given type of antibodies share common sequence properties?” and “If so, what are those properties?” In this work, three statistical tests designed to detect non‐random patterns in the amino acid makeup of a group of microarray peptides are presented. One test detects patterns of significantly biased amino acid usage, whereas the other two detect patterns of significant bias in the biochemical properties. These tests do not require a large number of peptides per group. The tests were applied to analyze 19 groups of peptides identified in immunosignaturing experiments as being specific for antibodies produced in response to various types of cancer and other diseases. The positional distribution of the biochemical properties of the amino acids in these 19 peptide groups was also studied. Remarkably, despite the random nature of the sequence libraries used to design the microarrays, a unique group‐specific non‐random pattern was identified in the majority of the peptide groups studied. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 318–329, 2016.
Redoubling the ring size of an endomorphin‐2 analog transforms a centrally acting mu‐opioid receptor agonist into a pure peripheral analgesic
Authors: Piekielna Justyna , De Marco Rossella , Gentilucci Luca , Cerlesi Maria Camilla , Calo' Girolamo , Tömböly Csaba , Artali Roberto , Janecka Anna
Published: April 2016

The study reports the synthesis and biological evaluation of two opioid analogs, a monomer and a dimer, obtained as products of the solid‐phase, side‐chain to side‐chain cyclization of the pentapeptide Tyr‐d‐Lys‐Phe‐Phe‐AspNH2. The binding affinities to the mu, delta, and kappa opioid receptors, as well as results obtained in a calcium mobilization functional assay are reported. Tyr‐[d‐Lys‐Phe‐Phe‐Asp]2‐NH2 1 was a potent and selective full agonist of mu with sub‐nanomolar affinity, while the dimer (Tyr‐[d‐Lys‐Phe‐Phe‐Asp]2‐NH2)2 2 showed a significant mixed mu/kappa affinity, acting as an agonist at the mu. Molecular docking computations were utilized to explain the ability of the dimeric cyclopeptide 2 to interact with the receptor. Interestingly, in spite of the increased ring size, the higher flexibility allowed 2 to fold and fit into the mu receptor binding pocket. Both cyclopeptides were shown to elicit strong antinociceptive activity after intraventricular injection but only cyclomonomer 1 was able to cross the blood–brain barrier. However, the cyclodimer 2 displayed a potent peripheral antinociceptive activity in a mouse model of visceral inflammatory pain. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 309–317, 2016.
Conformational flexibility of aspartame
Authors: Toniolo Claudio , Temussi Pierandrea
Published: April 2016

L‐Aspartyl‐L‐phenylalanine methyl ester, better known as aspartame, is not only one of the most used artificial sweeteners, but also a very interesting molecule with respect to the correlation between molecular structure and taste. The extreme conformational flexibility of this dipeptide posed a huge difficulty when researchers tried to use it as a lead compound to design new sweeteners. In particular, it was difficult to take advantage of its molecular model as a mold to infer the shape of the, then unknown, active site of the sweet taste receptor. Here, we follow the story of the 3D structural aspects of aspartame from early conformational studies to recent docking into homology models of the receptor. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 376–384, 2016.
Effects of linker sequence modifications on the structure, stability, and biological activity of a cyclic α‐conotoxin
Authors: Carstens Bodil B. , Swedberg Joakim , Berecki Géza , Adams David J. , Craik David J. , Clark Richard J.
Published: April 2016

The cyclic conotoxin analogue cVc1.1 is a promising lead molecule for the development of new treatments for neuropathic and chronic pain. The design of this peptide includes a linker sequence that joins the N and C termini together, improving peptide stability while maintaining the structure and activity of the original linear Vc1.1. The effect of linker length on the structure, activity and stability of cyclised conotoxins has been studied previously but the effect of altering the composition of the linker sequence has not been investigated. In this study, we designed three analogues of cVc1.1 with linker sequences that varied in charge, hydrophobicity and hydrogen bonding capacity and examined the effect on structure, stability, membrane permeability and biological activity. The three designed peptides were successfully synthesized using solid phase peptide synthesis approaches and had similar structures and stability compared with cVc1.1. Despite modifications in charge, hydrophobicity and hydrogen bonding potential, which are all factors that can affect membrane permeability, no changes in the ability of the peptides to pass through membranes in either PAMPA or Caco‐2 cell assay were observed. Surprisingly, modification of the linker sequence was deleterious to biological activity. These results suggest the linker sequence might be a useful part of the molecule for optimization of bioactivity and not just the physiochemical properties of cVc1.1. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 864–875, 2016.
Bioanalysis of antihistamines for clinical or forensic purposes
Authors: Katselou Maria , Papoutsis Ioannis , Nikolaou Panagiota , Spiliopoulou Chara , Athanaselis Sotiris
Published: April 2016

Antihistamines are a class of drugs that inhibit the action of histamine and are used to alleviate symptoms associated with allergic reactions, but some of them can cause side effects, the most unpleasant and dangerous of which are the sedative effects that may hinder important psychological functions and impair skilled performance. These side effects could decrease safety in certain common and critical tasks, such as driving or operating machinery, leading to accidents. Antihistamines can also cause intoxications, sometimes lethal, especially when co‐administered with alcohol or other sedative drugs. Thus, the development of analytical methods for their determination in biological fluids is considered to be useful for the investigation of clinical and forensic cases. These methodologies could also be used for pharmacokinetic studies. Several liquid and a few gas chromatographic methods have been developed for the determination of antihistamines in biological matrices after proper pretreatment procedures. This article reviews the published analytical methodologies that were gathered through the search in PubMed database and the recent developments on isolation or determination of antihistamines in biological materials. Current trends and future perspectives on bioanalysis of antihistamines are also discussed. Copyright © 2016 John Wiley & Sons, Ltd.
Compatible stability study of panax notoginseng saponin injection (xueshuantong®) in combination with 47 different injectables
Authors: Wang Meng , Zhang Huijie , Dong Ranran , Tan Lejun , Liu Zhidong , Zhu Yan , Gao Xiumei , Ren Xiaoliang
Published: April 2016

Panax Notoginseng Saponin (PNS) injection (Xueshuantong®, XST) plays an important role in acute and chronic treatment of cardiovascular disease in China. XST, a freeze‐dried powder injection of PNS, contains ginsenosides, Rg1, Rb1, Re, Rd. and notoginsenoside, R1. Study of the stability of herbal medicine injections is limited. The degradation products may contribute to adverse drug reactions (ADRs). The stability kinetics and degradation mechanisms of the five ingredients of PNS in XST injection were systematically explored in aqueous solution. The compatible stability of XST injection in combination with 47 injectables was evaluated using biophysical analysis. A principal components analysis model provided a good clustering result after compatibility. The degradation of the five ingredients in aqueous solution was found to be acid, temperature, oxidation and trivalent ion‐dependent. All ingredients were much more stable in XST injection than in aqueous solutions. Nine degradation products were identified by adopting LC‐Q‐TOF/MS. Standards exceeding the osmotic pressure and/or particle size were found to be the probable causes of the ADR, which were related to drug combination. To minimize the risk of ADRs, drug combinations should be avoided until the complicated chemical matrices of the Chinese medicine injections are more clearly understood. Copyright © 2016 John Wiley & Sons, Ltd.
Quantitative determination of regorafenib and its two major metabolites in human plasma with high‐performance liquid chromatography and ultraviolet detection
Authors: Fujita Kazuma , Miura Masatomo , Shibata Hiroyuki
Published: April 2016

A simple, highly sensitive and specific high‐performance liquid chromatography (HPLC) method was developed for the simultaneous quantitation of regorafenib, N‐oxidemetabolite (M‐2) and the desmethyl N‐oxide metabolite (M‐5) in human plasma. Regorafenib, M‐2, M‐5 and the internal standard sorafenib were separated using a mobile phase of 0.5% KH2PO4 (pH 3.5)–acetonitrile (30:70, v/v), on a Capcell PAK MG II column at a flow rate of 0.5 mL/min and measurement at UV 260 nm. The lower limits of quantification for regorafenib, M‐2 and M‐5 were 10 ng/mL for each analyte. A procedure using solid‐phase extraction required only a small amount of plasma (100 μL) for one analysis while providing high extraction recovery (>81% for all compounds) and good selectivity. Coefficients of variation for intra‐ and inter‐day assays were <12.2% for regorafenib, <12.3% for M‐2 and <15.1% for M‐5. Accuracies for intra‐ and inter‐day assays were <9.4% for regorafenib, <8.0% for M‐2 and <12.8% for M‐5 over a linear range from 10 to 10,000 ng/mL. This HPLC assay is suitable for clinical pharmacokinetic studies of regorafenib. The present HPLC method is currently in use for our observational studies of patients under treatment. Copyright © 2016 John Wiley & Sons, Ltd.
Predicting human intestinal absorption in the presence of bile salt with micellar liquid chromatography
Authors: Waters Laura J. , Shokry Dina S. , Parkes Gareth M.B.
Published: April 2016

Understanding intestinal absorption for pharmaceutical compounds is vital to estimate the bioavailability and therefore the in vivo potential of a drug. This study considers the application of micellar liquid chromatography (MLC) to predict passive intestinal absorption with a selection of model compounds. MLC is already known to aid prediction of absorption using simple surfactant systems; however, with this study the focus was on the presence of a more complex, bile salt surfactant, as would be encountered in the in vivo environment. As a result, MLC using a specific bile salt has been confirmed as an ideal in vitro system to predict the intestinal permeability for a wide range of drugs, through the development of a quantitative partition–absorption relationship. MLC offers many benefits including environmental, economic, time‐saving and ethical advantages compared with the traditional techniques employed to obtain passive intestinal absorption values. Copyright © 2016 John Wiley & Sons, Ltd.
The mystery of the thymus gland
Authors: Liu Daniel , Ellis Harold
Published: April 2016

The thymus is the last organ in the human body to have its mechanisms fully understood, having had its function fully delineated more than 50 years ago (Miller , Tissue Antigens 63:509–517). Prior to this, the thymus gland has had an interesting history with theories having included a role in fetal growth and development before becoming more sinisterly, a cause of sudden infant death in the late 19th century known as status lymphaticus (Paltauf , Wien Klin Wochenschr 2:877–881). Until Miller (, Lancet 278:748–749) eventually proved its primarily immunological role, the history of this mysterious gland has closely mirrored the history of medicine itself, troubling the minds of pathologists such as Virchow (, Ueber die Chlorose und die damit zusammenhängenden Anomalien im Gefässapparate, insbesondere über “Endocarditis puerperalis,” vorgetragen in der Sitzung der Berliner Geburtshülflichen Gesellschaft vom 12) and Grawitz (, Deut Med Wochenschr 22:429–431), surgeons such as Astley Cooper (, The Anatomy of the Thymus Gland) and Keynes (1953, Ann R Coll Surg 12:88), and eminent medical epidemiologists such as Greenwood and Woods [, J Hyg (Lond) 26:305–326]. This article will hopefully be of interest therefore to both clinician and historian alike. Clin. Anat. 29:679–684, 2016. © 2016 Wiley Periodicals, Inc.
Using Facebook to enhance learning experiences of students in computer programming at Introduction to Programming and Algorithm course
Authors: Özyurt Özcan , Özyurt Hacer
Published: April 2016

The purpose of this study is to evaluate the effect of using Facebook on enriching the learning experiences of students in programming learning. In another word, the aim of the study is to detect the reflections from the environment of programming learning where Facebook is used. The study was carried out within the scope of the Introduction to Programming and Algorithm course taught in the software engineering department of the technology faculty of a university in Turkey. Initially, a Facebook group was created to enrich classroom teaching. Sixty‐three freshman engineering students taking the course and the faculty members of the department joined the group. The study was conducted for one semester in the fall semester of the 2014–2015 academic year. The Educational Usage of Facebook Scale (EUFS) and semi‐structured interview form were used as data collection tools in the study. Quantitative data were descriptively analyzed while qualitative data were subjected to content analysis. The results obtained in this study show that Facebook has positive effects such as providing a rich content in programming learning, increasing extracurricular communication, offering a cooperative and collaborative learning environment, increasing motivation, and bringing different perspectives as well as negative effects such as causing distraction, decreasing face‐to‐face communication, and bringing about problems about expressing oneself. As a result, it is possible to assert that Facebook can be efficiently used to support classroom teaching strategies and enrich learning experiences in programming learning. © 2016 Wiley Periodicals, Inc. Comput Appl Eng Educ 24:546–554, 2016; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.21730
AGK‐BRAF gene fusion is a recurrent event in sporadic pediatric thyroid carcinoma
Authors: Cordioli Maria Isabel C. V. , Moraes Lais , Carvalheira Gianna , Sisdelli Luiza , Alves Maria Teresa S. , Delcelo Rosana , Monte Osmar , Longui Carlos A. , Cury Adriano N. , Cerutti Janete M.
Published: April 2016

Thyroid cancer is the fastest increasing cancer worldwide in all age groups. Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer in both adults and children. PTC genomic landscape has been extensively studied in adults, but information regarding sporadic pediatric patients is lacking. Although BRAF V600E mutation is highly prevalent in adults, this mutation is uncommon in pediatric cases. As adult and pediatric PTC is a mitogen‐activated protein kinase‐driven cancer, this altered pathway might be activated by different genetic events. The aim of this study was to investigate the occurrence of AGK‐BRAF fusion gene, recently described in radiation‐exposed pediatric PTC, in a cohort of exclusively sporadic pediatric PTC. The series consisted of 30 pediatric PTC younger than 18 years of age at the time of diagnosis and 15 matched lymph node metastases (LNM). Primary tumors and matched LNM were screened for the presence of the AGK‐BRAF fusion transcript by RT‐PCR. To confirm the identity of the amplified products, randomly selected samples positive for the presence of the fusion transcripts were sequenced. Moreover, BRAF dual‐color, break‐apart probes confirmed BRAF rearrangement. Overall, the AGK‐BRAF fusion gene was detected in 10% (3/30) of primary tumors. For one of these cases, paired LNM was also available, which also shows the presence of AGK‐BRAF fusion gene. This study described, for the first time, the presence of AGK‐BRAF in sporadic pediatric PTC. Understanding the molecular events underlying pediatric PTC may improve preoperative diagnosis, allow molecular prognostication and define a therapeutic approach toward sporadic PTC patients.
The real role of pseudokinase: linking diabetes to cancers
Authors: Li Ke , Hu Zhuowei
Published: April 2016

A recent paper in Nature Communications shows that pseudokinase TRIB3 has a critical role in the development of diabetes‐related cancers via interacting with SQSTM1, a selective autophagy receptor. Interrupting the TRIB3‐SQSTM1 interaction using an α‐helix peptide shows a significant antitumor effect both in normal and diabetic mice. This work provides a potential strategy against cancers in patients with diabetes.
Chemical Diversity and Antimicrobial Activity of Salvia multicaulis Vahl Essential Oils
Authors: Fahed Layal , Stien Didier , Ouaini Naïm , Eparvier Véronique , El Beyrouthy Marc
Published: April 2016

The chemical compositions and antimicrobial activities of the essential oils (EOs) of aerial parts of Salvia multicaulis Vahl, collected during the same week from two different Lebanese regions, were investigated. The EOs were obtained by hydrodistillation using a Clevenger‐type apparatus and characterized by GC and GC/MS analyses. The minimum inhibitory concentrations of these EOs were determined against one Gram‐negative and two Gram‐positive bacteria, one yeast, and five dermatophytes using the broth microdilution technique. One EO was notably active against Staphylococcus aureus, methicillin‐resistant S. aureus, and all of the Trichophyton species tested. Nerolidol was found to be the major compound in the active oil; nerolidol was also absent from the inactive oil. This study demonstrated that nerolidol shows antimicrobial activity and therefore significantly contributes to the antimicrobial potential of the oil. The chemical diversity of worldwide S. multicaulis EOs was analyzed, revealing that the EOs of this study belong to two different chemotypes found in the literature. The nerolidol chemotype appears to be restricted to Lebanon, and it can be used as antimicrobial agent against external bacterial and fungal infections.
Multiplexed Imaging of Protein Phosphorylation on Membranes Based on TiIV Functionalized Nanopolymers
Authors: Iliuk Anton , Li Li , Melesse Michael , Hall Mark C. , Tao W. Andy
Published: April 2016

Accurate protein phosphorylation analysis reveals dynamic cellular signaling events not evident from protein expression levels. The most dominant biochemical assay, western blotting, suffers from the inadequate availability and poor quality of phospho‐specific antibodies for phosphorylated proteins. Furthermore, multiplexed assays based on antibodies are limited by steric interference between the antibodies. Here we introduce a multifunctionalized nanopolymer for the universal detection of phosphoproteins that, in combination with regular antibodies, allows multiplexed imaging and accurate determination of protein phosphorylation on membranes.
Unexpected Photo‐instability of 2,6‐Sulfonamide‐Substituted BODIPYs and Its Application to Caged GABA
Authors: Takeda Aoi , Komatsu Toru , Nomura Hiroshi , Naka Masamitsu , Matsuki Norio , Ikegaya Yuji , Terai Takuya , Ueno Tasuku , Hanaoka Kenjiro , Nagano Tetsuo , Urano Yasuteru
Published: April 2016

Investigation of the unexpected photo‐instability of 2,6‐sulfonamide‐substituted derivatives of the boron dipyrromethene (BODIPY) fluorophore led to the discovery of a photoreaction accompanied by multiple bond scissions. We characterized the photoproducts and utilized the photoreaction to design a caged γ‐aminobutyric acid (GABA) derivative that can release GABA upon irradiation in the visible range (>450 nm). This allowed us to stimulate neural cells in mouse brain slices.
Adaptation and Diversification of an RNA Replication System under Initiation‐ or Termination‐Impaired Translational Conditions
Authors: Mizuuchi Ryo , Ichihashi Norikazu , Yomo Tetsuya
Published: April 2016

Adaptation to various environments is a remarkable characteristic of life. Is this limited to extant complex living organisms, or is it also possible for a simpler self‐replication system to adapt? In this study, we addressed this question by using a translation‐coupled RNA replication system that comprised a reconstituted translation system and an RNA “genome” that encoded a replicase gene. We performed RNA replication reactions under four conditions, under which different components of translation were partly inhibited. We found that replication efficiency increased with the number of rounds of replication under all the tested conditions. The types of dominant mutations differed depending on the condition, thus indicating that this simple system adapted to different environments in different ways. This suggests that even a primitive self‐replication system composed of a small number of genes on the early earth could have had the ability to adapt to various environments.
The impact of US Government assistance on recidivism
Authors: Costopoulos Julie S. , Plewinski Amy M. , Monaghan Patricia L. , Edkins Vanessa A.
Published: April 2016

Background

Community re‐entry from custody programmes facilitate access to community resources, such as cash assistance and food stamps, with the aim of reducing criminal recidivism. Evidence that these programmes achieve is mainly from longer‐term prisoners rather than short‐term jail inmates.

Aim

The aim of the study is to test the hypothesis that facilitating access to community resources while still in jail would reduce re‐arrest rates among former jail inmates in the USA.

Methods

Community resources offered to the jail inmates participating in this study included Medicaid, food stamps and cash assistance. Participants who opted to sign up for these social services were matched with non‐applicants based on date of release (n = 101). Each participant's criminal history was coded prior to release from the jail and at three months, six months and one year after release.

Results

Contrary to our original hypotheses, recidivism was not significantly reduced in the applicant group. People released after facilitated access to community assistance had an increase in drug offence severity at six months after release. Recidivism also differed by age and race.

Conclusion

The substance offences in the applicant group suggested that cash benefits provided the released offender with the means to sustain their substance misuse. Treatment for substance misuse should be incorporated with other resources in order to reduce recidivism effectively. Copyright © 2016 John Wiley & Sons, Ltd.
Aortic annulus to left coronary distance as a predictor for persistent left bundle branch block after TAVI
Authors: Hein‐Rothweiler Ralph , Jochheim David , Rizas Konstantinos , Egger Alexander , Theiss Hans , Bauer Axel , Massberg Steffen , Mehilli Julinda
Published: April 2016

Objectives

To identify potential predictors for ventricular conduction delay and to evaluate the impact of interventricular dyssynchrony on mortality after implantation of a balloon‐expandable aortic valve (BEV).

Methods and results

Clinical, computertomographical (CT), and electrocardiographical (ECG) data from 225 transcatheter aortic valve implantation (TAVI) patients were analyzed. Procedures were performed between May 2010 and September 2013 via transfemoral access using a BEV. Incidence of new‐onset left bundle branch block (NOP‐LBBB) at discharge was 23.1% (n = 52). Predictive factors for NOP‐LBBB were first degree atrioventricular (AV) block (odds ratio (OR): 3.91, 95% confidence interval (CI): 1.58 to 9.64), area cover index (OR: 1.83, 95% CI: 1.26 to 2.67), annulus calcification > first degree (OR: 3.01, 95% CI: 1.36 to 6.66), and annulus to left coronary distance (OR: 0.65, 95% CI: 0.44 to 0.96). At 1‐year follow‐up, no significant difference was observed concerning all‐cause mortality (15.6% among non NOP‐LBBB and 9.6% among NOP‐LBBB patients, P = 0.278) and cardiovascular mortality (4.6% among non NOP‐LBBB and 5.8% among NOP‐LBBB patients, P = 0.737).

Conclusion

In addition to previous predictors, annulus to left coronary distance and area cover index have been identified as new predictors for NOP‐LBBB. NOP‐LBBB showed no relevant impact on mortality after one year. Further investigation including larger populations and longer follow‐up is required to confirm these findings and develop an algorithm for identification of patients at risk for NOP‐LBBB associated adverse events. © 2016 Wiley Periodicals, Inc.
Comparison of transradial coronary procedures via right radial versus left radial artery approach: A meta‐analysis
Authors: Shah Rachit M. , Patel Dhavalkumar , Abbate Antonio , Cowley Michael J. , Jovin Ion S.
Published: April 2016

Introduction

Coronary angiography and angioplasty via transradial approach is shown to be associated with significant reduction in access site complications. Due to a lack of sufficient data, the use of the right or left radial approach is still operator‐dependent. We performed a meta‐analysis of prospective randomized studies to compare right versus left radial artery approach for coronary procedures.

Methods

We found 12 randomized studies meeting the predetermined inclusion criteria. A total of 6,450 patients were included in the meta‐analysis of which 3,217 patients underwent coronary procedures via right radial approach and 3,233 patients via left radial approach. The primary endpoint was the comparison of fluoroscopy time, procedure time, contrast use and cross‐over rates between two radial approaches.

Results

Pooled analysis of the included studies showed a similar rate of cross‐over events (4.2% for right radial approach vs. 4.1% for left radial approach, odds ratio (OR)=1.08, P = 0.68), and similar total procedure times (18.8 ± 10.3 min vs. 18.1 ± 10.0 min, standard difference (SD) of the mean = 0.09, P = 0.162) between the two radial approaches. However, the right radial approach was found to be associated with minimally longer fluoroscopy times (5.8 ± 4.4 min vs. 5.3 ± 4.2 min, SD of the mean = 0.157, P < 0.001) and greater contrast use (84 ± 35 mL vs. 82 ± 34 mL, SD of the mean = 0.082, P = 0.003). Access site complications and the incidence of stroke were similar between two radial approaches.

Conclusion

Our meta‐analysis suggests a small but statistically significant difference in terms of contrast use and fluoroscopy time in favor of coronary procedures performed via left radial approach in comparison to right radial approach without any significant difference in access site or other procedural complications between the two radial approaches. © 2016 Wiley Periodicals, Inc.