bluuebunny/crossref_metadata_2025 huggingface dataset:
Flavoenzymes: Covalent versus Noncovalent
Authors: Starbird Chrystal A , Maklashina Elena , Cecchini Gary , Iverson TM
Published: September 2015

The use of nonprotein cofactors by enzymes expands the range of biological chemistries supported in nature. Flavins, which are derivatives of vitamin B2, are highly conjugated rings that are particularly useful for oxidoreduction and group transfer reactions. Most flavins are noncovalently associated with their enzymes, but around 10% of flavoproteins have the flavin covalently attachedin vivo. Extensive research has investigated how the presence of the covalent bond between enzyme and flavin cofactor influences enzymatic catalysis. This work identified that the primary roles of the covalent flavin are to allow catalysis of more thermodynamically challenging reactions and to prevent the cofactor from disassociating from the enzyme. Major questions in the field now include the mechanism of covalent flavinylation. The earliest studies on a subset of covalent flavoproteins suggested that cofactor attachment could be an autocatalytic posttranslational process. However, the recent identification of assembly factors that promote covalent flavinylation identifies that ancillary proteins may be important for covalent flavinylationin vivo.

Key Concepts

Covalent flavin attachment increases stability of the holoenzyme and increases the enzyme's redox potential.

Covalent flavinylation may occur either through an entirely autocatalytic mechanism, or be assisted by assembly factors.

Enzyme‐associated flavin can promote a variety of chemistries.

Flavoenzymes can have covalent or noncovalent flavin.

Covalent flavinylation can occur on multiple sites of the protein and flavin molecule.
M
Cells
Authors: Mabbott Neil A , Sehgal Anuj , Donaldson David S
Published: September 2015

The mucosal immune system in the gastrointestinal tract helps protect against orally acquired pathogens. To efficiently do this, the mucosal immune system must be able to sample the gut lumenal contents to enable it to generate protective immune responses against pathogens. The transport of luminal antigens across mucosal epithelia is a key initial step in the induction of an efficient mucosal immune response. Here, we discuss how a unique population of epithelial cells termed M cells (or ‘microfold’ cells) enables the mucosal immune system to efficiently sample the intestinal contents. We describe the characteristic features of M cells; describe the molecular and cellular factors that influence their differentiation and functional maturation; discuss how lumenal antigens are sampled by M cells and also how the specific targeting of antigens to M cells may represent a novel method to induce antigen‐specific mucosal immunity.

Key Concepts

The mucosal immune system in the gastrointestinal and respiratory tracts acts to protect against pathogens acquired by ingestion and inhalation, respectively.

The transport of luminal antigens across mucosal epithelia is a key initial step in the induction of an efficient mucosal immune response.

M cells are a unique population of epithelial cells which are specialised for the transcytosis of a broad range of materials such as particulate antigens, soluble macromolecules, pathogens and secretory IgA across the gut epithelium into the gut‐associated lymphoid tissues.

The efficient transcytosis of antigens by M cells is an important first step in the induction of efficient mucosal immune responses to certain pathogenic microorganisms.

M cells derive from Lgr5
+
stem cells in the intestinal crypts.

Stimulation via the cytokine RANKL and the subsequent intrinsic expression of distinct transcription factors specifically trigger the differentiation of the Lgr5
+
stem‐cell‐derived proliferative daughter cells into mature, functional M cells.

The sampling of lumenal antigens by M cells may occur in a nonselective manner (e.g. via constitutive micropinocytosis). However, M cells also appear to express a range of ‘immunosurveillance’ receptors suggesting that some antigens are acquired specifically via receptor‐mediated endocytosis.

The specific targeting of vaccine antigens may represent novel strategies to develop mucosal vaccines and induce mucosal immunity.

Aging has a dramatic influence on the functional maturation of M cells.
Psychopharmacology
Authors: Miles Samuel I.
Published: September 2015

This article is an outline of basic principles of psychopharmacology, and an overview of psychotherapeutic agents, along with some clinical and medical‐legal issues related to them.
Genomics and Behavioral Evidence
Authors: Bernet William
Published: September 2015

This article summarizes the history and current status of testimony regarding behavioral genetics and genomics. Depending on the case specifics, testimony regarding a person's genetic make‐up may constitute evidence of a particular psychiatric diagnosis, may simply support the diagnosis in a general way, or may help explain the person's behavior. In criminal trials, testimony regarding behavioral genomics—including gene and environment interactions—is most likely to be relevant as mitigation in sentencing hearings. Ordinarily, genotyping a defendant is only one part of a comprehensive psychiatric and psychological forensic evaluation.
Psychopharmacology: Child and Adolescent
Authors: Shapiro Desiree N. , Stahl Stephen M.
Published: September 2015

This article reviews the role and use of psychiatric medications in children and adolescents suffering from mental illness. Issues regarding treatment approaches, treatment planning, legal concerns, and decision making are addressed. Commonly used medications are reviewed.
Synthesis of Pyridoisoindoles through Diazotization Followed by Intramolecular Cyclization from Pyridinylarylacetates in One Pot
Authors: Kim Cheol‐Eui , Baek Yonghyeon , Kim Sung Hong , Lee Phil Ho
Published: September 2015

A robust synthetic method for a variety of pyridoisoindoles from pyridinylarylacetates has been developed through diazotization using 4‐methylbenzenesulfonyl azide and 1,8‐diazabicyclo[5.4.0]undec‐7‐ene followed by intramolecular cyclization via elimination of a nitrogen molecule under copper(II) trifluoromethanesulfonate‐catalyzed conditions in a one‐pot process. The intramolecular cyclization also took place efficiently with diazo substrates to produce pyridoisoindoles in good to excellent yields under metal‐free conditions or catalytic conditions [1.0 mol% copper(II) trifluoromethanesulfonate, 25 °C].

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Analysis of Thermal Diodes Enabled by Junctions of Phase Change Materials
Authors: Cottrill Anton L. , Strano Michael S.
Published: September 2015

Materials designed to undergo a phase transition at a prescribed temperature have been advanced as elements for controlling thermal flux. Such phase change materials can be used as components of reversible thermal diodes, or materials that favor heat flux in a preferred direction; however, a thorough mathematical analysis of such diodes is thus far absent from the literature. Herein, it is shown mathematically that the interface of a phase change material with a phase invariant one can function as a simple thermal diode. Design equations are derived for such phase change diodes, solving for the limits where the transition temperature falls within or outside of the temperature gradient across the device. Criteria are derived analytically for the choice of thermal conductivity of the invariant phase to maximize the rectification ratio. Finally, the model is applied to several experimental systems in the literature, providing bounds on observed performance. This model should aid in the development of materials capable of controlling heat flux.
A panel data analysis of the probability of childbirth in aJapanese sample: New evidence of the two‐child norm
Authors: Morita Masahito , Ohtsuki Hisashi , Hiraiwa‐Hasegawa Mariko
Published: September 2015

Objectives

To reveal the conditions that could facilitate childbirth in modern humans, it is necessary to analyze not only cross‐sectional surveys but also panel data that track the same person for a long period. In this study, we analyzed factors that would influence the probability of childbirth.

Methods

We analyzed Japanese panel data with a Cox proportional hazard model. Subjects of our analysis were married women and their childbirth records from 2004 to 2009.

Results

Contrary to the predictions based on the theory of behavioral ecology, we found no positive relationship between good parental conditions for childcare, such as high income, increase in income, or coresidence with parents (i.e., grandparents of children), and the occurrence of childbirth. We found that the number of existing children had a significant impact on the probability of childbirth. The likelihood of further childbirth by couples with one child was nearly equal to that of childless ones. However, the corresponding likelihood of couples with two children was about five times lower than that of childless ones.

Conclusions

The total fertility rates in modern developed societies are quite low and couples prefer having two children. This trend is known as the two‐child norm, but it is a paradoxical phenomenon in terms of fitness maximization. Our result provided new quantitative evidence of this norm. This study revealed that the number of existing children being less than two was one of the factors associated with further childbearing in our Japanese sample. Am. J. Hum. Biol. 28:220–225, 2016. © 2015 Wiley Periodicals, Inc.
Rapid Access to New Thiazepinyl and Oxazepinyl Phosphonates through a Green Pudovik Reaction
Authors: Saha Debasmita , Kaur Tanpreet , Singh Neetu , Singh Udai P. , Sharma Anuj
Published: September 2015

A simple, facile, and efficient microwave‐assisted synthetic protocol for the preparation of novel dibenzothiazepinyl and dibenzoxazepinyl phosphonates has been reported. The present Pudovik approach works without a catalyst or solvent to furnish cyclic α‐amino phosphonates by using dibenzothia‐ and dibenzoxazepines as imine substrates. This method has a greener edge and is amenable to large‐scale production.
Quantitative assessment of skin, hair, and iris variation in a diverse sample of individuals and associated genetic variation
Authors: Norton Heather L. , Edwards Melissa , Krithika S. , Johnson Monique , Werren Elizabeth A. , Parra Esteban J.
Published: September 2015

Objectives

The main goals of this study are to 1) quantitatively measure skin, hair, and iris pigmentation in a diverse sample of individuals, 2) describe variation within and between these samples, and 3) demonstrate how quantitative measures can facilitate genotype‐phenotype association tests.

Materials and Methods

We quantitatively characterize skin, hair, and iris pigmentation using the Melanin (M) Index (skin) and CIELab values (hair) in 1,450 individuals who self‐identify as African American, East Asian, European, Hispanic, or South Asian. We also quantify iris pigmentation in a subset of these individuals using CIELab values from high‐resolution iris photographs. We compare mean skin M index and hair and iris CIELab values among populations using ANOVA and MANOVA respectively and test for genotype‐phenotype associations in the European sample.

Results

All five populations are significantly different for skin (P <2 × 10−16) and hair color (P <2 × 10−16). Our quantitative analysis of iris and hair pigmentation reinforces the continuous, rather than discrete, nature of these traits. We confirm the association of three loci (rs16891982, rs12203592, and rs12913832) with skin pigmentation and four loci (rs12913832, rs12203592, rs12896399, and rs16891982) with hair pigmentation. Interestingly, the derived rs12203592 T allele located within the IRF4 gene is associated with lighter skin but darker hair color.

Discussion

The quantitative methods used here provide a fine‐scale assessment of pigmentation phenotype and facilitate genotype‐phenotype associations, even with relatively small sample sizes. This represents an important expansion of current investigations into pigmentation phenotype and associated genetic variation by including non‐European and admixed populations. Am J Phys Anthropol 160:570–581, 2016. © 2015 Wiley Periodicals, Inc.
Hadza hunter‐gatherer men do not have more masculine digit ratios (2D:4D)
Authors: Apicella Coren L. , Tobolsky Victoria A. , Marlowe Frank W. , Miller Kathleen W.
Published: September 2015

Objectives

The ratio between the length of the second and the length of the fourth digit (2D:4D) is sexually dimorphic such that males of many species possess a lower ratio than females, particularly in the right hand. Still, men and women often exhibit overlapping 2D:4D ranges and the ratio is highly variable between populations. In order to further explore populational variability, we chose to analyze 2D:4D in the Hadza, a population of hunter‐gatherers living in Tanzania.

Materials and Methods

Data were collected separately by two researchers over the course of three years (1998, 2001, 2006) from 152 adult participants (male: n = 76, female: n = 76). Independent samples t‐tests were used to explore sex differences, paired samples t‐tests were used to explore directional effects within each sex, and linear regression and one‐way ANOVA were used to test possible age effects.

Results

In none of the years, or pooled (n = 152), did we find evidence that adult men have a lower 2D:4D than adult women. If anything, the data suggest that women in this population have a significantly lower right hand 2D:4D than men (P < 0.001, d = 0.57). In contrast, left hand 2D:4D did not exhibit a sex difference (P = 0.862, d = 0.03).

Discussion

These findings challenge the current view that lower 2D:4D in men is a uniform characteristic of our species. Cross‐populational variance in 2D:4D may be related to known patterns of hormonal variation resulting from both genetic and environmental mechanisms, though this relationship merits further investigation. Am J Phys Anthropol 159:223–232, 2016. © 2015 Wiley Periodicals, Inc.
Poly (glycerol‐sebacate) bioelastomers: 2. Synthesis using Brabender Plasticoder® as a batch reactor
Authors: Maliger Raju B. , Halley Peter J. , Cooper‐White Justin J.
Published: September 2015

Poly (glycerol‐sebacate) polymers are seen as useful materials for biomedical applications. In this article, poly (glycerol‐sebacate) oligomers were synthesized by modifying a Brabender Plasticorder® as a batch reactor. The samples collected over a reaction period of 5 h were characterized using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The number‐average molecular weight (Mn) and weight‐average molecular weight (Mw) of the oligoesters were determined using matrix‐assisted laser desorption/ionization time‐of‐flight spectroscopy (MALDI‐TOF). The polydispersity indices of these oligoesters produced were within bounds of current commercial polymers. The gel‐point of the reaction was determined from the crossover point of the storage and loss moduli, and the reaction rate constant was calculated using the torque data of the rheometer. The kinetic rate constant and the extent of the reaction in the Brabender were higher than the corresponding values obtained from the conventional laboratory reaction process. The challenges and possibilities in scaling up a batch process to a continuous process (e.g., reactive extrusion) are discussed. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 132, 42852.
Is there value in chemical modification of fish scale surfaces?
Authors: Xiang Xu , Long Fei , Narkar Ameya , Kinnunen Ronald E. , Shahbazian‐Yassar Reza , Lee Bruce P. , Heiden Patricia A.
Published: September 2015

Fish scales are an abundant biowaste apparently unused, except for isolating major components as feedstocks, sacrificing the useful properties inherent to scales. We modified scale surfaces using hydrophilic and hydrophobic (meth)acrylates and tetraethylorthosilicate with in situ polymerization, and partial degradation of the biomineral or collagen layer. Chemical changes were assessed qualitatively by Fourier‐transform infrared spectroscopy and quantitatively by nanomechanical analysis. No modification was selective but they were “preferential”. Hydrophobic modifications were inefficient and reduced scale modulus. Inorganic and hydrophilic modifications were efficient and increased modulus. On adding sodium‐citrate‐modified scales to a weak alginate hydrogel, rheology showed an order of magnitude increase in storage modulus compared to alginate with no or unmodified scale reinforcement. Fish scales can be a useful new reinforcement. This work highlights simple pathways to manipulate surface composition and modulus of waste fish scale to enhance composite properties. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 42868.
Chinese Overseas Hydropower Dams and Social Sustainability: The Bui Dam in Ghana and the Kamchay Dam in Cambodia
Authors: Urban Frauke , Nordensvard Johan , Siciliano Giuseppina , Li Bingqin
Published: September 2015

There is a shortage of empirical studies on the relationship between Chinese hydropower dams and social sustainability. Comparative research on Chinese‐funded and Chinese‐built hydropower projects is rare. This article aims to fill parts of this gap by discussing these issues in relation to Chinese overseas hydropower dams in Ghana (Bui Dam) and Cambodia (Kamchay Dam). Both projects are built by Sinohydro and financed by ExIm Bank. This article draws on in‐depths interviews and focus group discussions with local communities affected by the dams, institutional actors in Ghana and Cambodia, Chinese actors, and dam builders. The article uses an environmental justice perspective as an analytical framework. The article concludes that the dam projects could improve their social sustainability framework in practice and theory; social benchmarking should be introduced and social policies need to be improved to be in line with international social standards on hydropower projects.
Age of Choice: How Partner Countries Are Managing the New Development Assistance Landscape—The Cases ofFiji,PapuaNewGuinea,Timor‐Leste andVanuatu
Authors: Schmaljohann Maya , Prizzon Annalisa
Published: September 2015

Based on a comparative case study approach, the article reviews trends in volumes and modalities of non‐traditional development assistance flows since 2003 (from emerging countries, philanthropic organisations and the private sector) for the governments ofFiji,PapuaNewGuinea,Timor‐Leste andVanuatu, and elaborates on the governments' priorities regarding the terms and conditions of development assistance flows and the impact on aid coordination of new providers. We found that the amount of non‐traditional development assistance has strongly increased inFiji but less so inPapuaNewGuinea,Timor‐Leste andVanuatu. Capacity building for government officials—both in the negotiation and management of these flows—is a priority aspect for development assistance for all of the four analysed governments, even forPapuaNewGuinea where the government introduced a target to reduce technical assistance, aiming to a more efficient use of this modality and improved knowledge transfer to government officials.
How Income Segmentation Affects Income Mobility: Evidence from Panel Data in the Philippines
Authors: Martinez Arturo , Western Mark , Haynes Michele , Tomaszewski Wojtek
Published: September 2015

Despite vibrant economic growth, the Philippines confronts persistently high income inequality. Using household‐level panel data collected for the years 2003, 2006 and 2009, we investigate how income segmentation affects Filipinos' income mobility prospects. The results of the multinomial logistic models suggest that if households are grouped according to initial income (in 2003), richer households had the lowest propensity to experience slow to moderate income changes and were most likely to experience consistently downward mobility from 2003 to 2009, while initially poorer households had the highest propensity to experience consistently upward mobility. On the other hand, if households are grouped according to permanent income, we still find that lower income households experienced (slightly) better income mobility outcomes; however, their edge over higher income households was much smaller than when initial income was used. This result could indicate that convergence on the basis of initial income may be in part random variation. The findings are robust to heuristic and model‐based methods of grouping households into different income segments.
Gold/Palladium Alloy for Carbon–Halogen Bond Activation: An Unprecedented Halide Dependence
Authors: Dhital Raghu Nath , Bobuatong Karan , Ehara Masahiro , Sakurai Hidehiro
Published: September 2015

New catalytic activity of gold/palladium alloy nanoclusters (NCs) for carbon–halogen bond activation is demonstrated. In the case of an aryl chloride, the inclusion of gold in a bimetallic catalyst is indispensable to achieve the coupling reactions. Gold has the unique effect of stabilizing palladium, such that Pd2+ leached from clusters by means of spillover of chloride during oxidative addition. The thus‐formed spillover intermediate further reacts heterogeneously in both Ullmann and Suzuki‐type coupling reactions through a new type of mechanism. In the case of an aryl bromide, Ullmann coupling occurs through the spillover of bromide, similar to that of aryl chloride. However, a significant fraction of palladium also leached, which diminished the Ullmann coupling activity of the aryl bromide and, as a result, the order of reactivity was ArCl>ArBr. With regard to the activation of the C−Br bond towards a Suzuki‐type reaction, the inclusion of a higher gold content in gold/palladium clusters stabilized palladium to prevent the leaching of Pd2+ from the clusters by means of spillover of bromide. The spillover intermediate reacts heterogeneously with PhB(OH)2, palladium‐rich gold/palladium, or pure palladium clusters; the oxidative addition of ArBr favors the extraction of palladium from the clusters, yielding Pd2+ intermediates. The extracted intermediates react homogenously (Pd2+/Pd0 catalysis) with PhB(OH)2, which results in the higher selectivity of the cross‐coupling product. An initial step to observe such unprecedented halide dependency, together with the dynamic behavior of palladium on the surface of gold is the oxidative addition of Ar−X. A detailed insight into the first oxidative addition process was also examined by quantum chemical calculations.
Retrograde approach to an ostial left anterior descending chronic total occlusion through a left internal mammary artery graft
Authors: Hari Pawan , Kirtane Ajay J. , Bangalore Sripal
Published: September 2015

Retrograde approach to chronic total occlusions (CTO) has been described via saphenous vein grafts, septal and epicardial collaterals. We report for the first time a successful retrograde approach to an ostial left anterior descending (LAD) artery CTO through a failed left internal mammary artery (LIMA) to LAD anastamosis. This case demonstrates the technical aspects of using a LIMA conduit as a retrograde approach to CTO. © 2015 Wiley Periodicals, Inc.
Sheathless guide catheter in transradial percutaneous coronary intervention for ST‐segment elevation myocardial infarction
Authors: Miyasaka Masaki , Tada Norio , Kato Shigeaki , Kami Masahiro , Horie Kazunori , Honda Taku , Takizawa Kaname , Otomo Tatsushi , Inoue Naoto
Published: September 2015

Objectives

The aim of this study was to assess the safety and efficacy of sheathless guide catheters in transradial percutaneous coronary intervention (PCI) for ST‐segment elevation myocardial infarction (STEMI).

Background

Transradial PCI for STEMI offers significant clinical benefits, including a reduced incidence of vascular complications. As the size of the radial artery is small, the radial artery is frequently damaged in this procedure using large‐bore catheters. A sheathless guide catheter offers a solution to this problem as it does not require an introducer sheath. However, the efficacy and safety of sheathless guide catheters remain to be fully determined in emergent transradial PCI for STEMI.

Methods

Data on consecutive STEMI patients undergoing primary PCI at the Sendai Kousei Hospital between September 2010 and May 2013 were analyzed. The primary endpoint was the rate of acute procedural success without access site crossover. Secondary endpoints included door‐to‐balloon time, fluoroscopy time, volume of contrast, and radial artery stenosis or occlusion rate.

Results

We conducted transradial PCI for 478 patients with STEMI using a sheathless guide catheter. Acute procedural success was achieved in 466 patients (97.5%). The median door‐to‐balloon time was 45 min (range, 15–317 min). The median fluoroscopy time was 16.4 min (range, 10–90 min). The median volume of contrast was 134 mL (range, 31–431 mL). Radial stenosis or occlusion developed in 14 (3.8%) of the 370 evaluable patients.

Conclusions

This study showed that use of a sheathless guide catheter taking a transradial approach was effective and safe in primary PCI for STEMI. © 2015 Wiley Periodicals, Inc.
Evaluation of the efficacy and safety of dual antiplatelet therapy with or without warfarin in patients with a clinical indication for DAPT and chronic anticoagulation: A meta‐analysis of observational studies
Authors: Bavishi Chirag , Koulova Anna , Bangalore Sripal , Sawant Ashwin , Chatterjee Saurav , Ather Sameer , Valencia Jose , Sarafoff Nikolaus , Rubboli Andrea , Airaksinen Juhani K. , Lip Gregory Y. H. , Tamis‐Holland Jacqueline E.
Published: September 2015

Objective

To compare the efficacy and safety of dual antiplatelet therapy (DAPT) and triple therapy (TT, dual antiplatelet plus warfarin) in patients with myocardial infarction (MI) or PCI with stenting (PCI‐S) who also require chronic oral anticoagulation. Background: Recommendations for the optimal antiplatelet/anticoagulant treatment regimen for patients undergoing PCI‐S or MI who also require oral anticoagulation are largely based on evidence from observational studies and expert opinions. Methods: A systematic search was performed for studies comparing TT vs. DAPT in patients post PCI‐S or MI and requiring chronic anticoagulation. Primary outcome was all‐cause mortality. Secondary outcomes were ischemic stroke, major bleeding, MI, and stent thrombosis. Pooled relative risks (RR) were calculated using random effects model. Results: A total of 17 studies were included, with 14,921 patients [TT: 5,819(39%) and DAPT: 9,102(61%)] and a mean follow‐up of 1.6 years. The majority of patients required oral anticoagulation for atrial fibrillation. Compared to DAPT, patients treated with TT had no significant difference in all‐cause mortality [RR: 0.81, 95% confidence interval (CI): 0.61–1.08, P = 0.15], MI [RR 0.74, 95% CI: 0.51–1.06, P = 0.10], and stent thrombosis [RR 0.67, 95% CI: 0.35–1.30, P = 0.24]. Patients treated with TT had significantly increased risk of major bleeding [RR 1.20, 95% CI: 1.03–1.39, P = 0.02], whereas the risk for ischemic stroke was significantly lower [RR 0.59, 95% CI: 0.38‐0.92, P = 0.02]. Conclusions: All‐cause mortality appears similar in patients treated with TT or DAPT although TT was associated with higher rates of major bleeding and a lower risk for ischemic stroke. © 2015 Wiley Periodicals, Inc.
Left atrial appendage closure: First in man with the 4th generation watchman device
Authors: Ledwoch Jakob , Franke Jennifer , Gonzaga Maik , Bertog Stefan , Braut Annkathrin , Hofmann Ilona , Vaskelyte Laura , Gafoor Sameer , Reddy Vivek , Sievert Horst
Published: September 2015

Objectives

To evaluate the feasibility and safety of the fourth generation WATCHMAN device.

Background

The WATCHMAN left atrial appendage (LAA) closure device has been shown to be non‐inferior to conventional oral anticoagulation with warfarin for stroke prevention in patients with non‐valvular atrial fibrillation. A new (fourth) generation of the WATCHMAN device was designed to facilitate easier delivery and improve safety.

Methods

We conducted a prospective, non‐randomized study of LAA closure with use of the 4th generation WATCHMAN device in 36 patients with non‐valvular atrial fibrillation. Follow‐up was performed at 45 days, 6 months and 12 months following implantation.

Results

The mean age of the population was 73 ± 6 years and 67% were male. The mean CHADS2 and CHA2DS2‐VASc Score were 2.5 and 4.5, respectively. The device was implanted successfully in 34/36 (94%). No serious hospital complications related to the device or procedure occurred. During 12 month follow‐up, three ischemic strokes (8%), one hemorrhagic stroke (3%), one TIA (3%) and three deaths (9%) occurred. Device‐associated thrombus formation was detected in one patient (3%) during six‐month follow‐up and was treated successfully with low molecular weight heparin.

Conclusions

LAA closure with the 4th generation WATCHMAN device is feasible and safe. New technical features may contribute to a better performance of the occluder, particularly regarding the risk of pericardial effusions. © 2015 Wiley Periodicals, Inc.
Electrogenerated Chemiluminescence Reporting on Closed Bipolar Microelectrodes and the Influence of Electrode Size
Authors: Oja Stephen M. , Zhang Bo
Published: September 2015

We report a fundamental study on the use of Ru(bpy)32+‐based electrogenerated chemiluminescence (ECL) as an optical reporting system for the detection of redox‐active analytes on closed bipolar microelectrodes, focused on gaining an in‐depth understanding of the correlation between the ECL emission intensity and the electrochemical current. We demonstrate the significant effect that the size of the anodic and cathodic poles has on the resulting ECL signal and show how this influences the quantitative detection of an analyte on a closed bipolar electrode. By carefully designing the geometry of the bipolar electrode, the detection performance of the system can be tuned to different analyte concentration ranges. We show that, through a simple voltammetric study of the individual reactions, one can understand the coupled bipolar behavior and accurately predict the ECL signal response to a range of analyte concentrations, enabling the accurate prediction of calibration curves.
ChemInform Abstract: Regioselective Hetero‐Michael Addition of Oxygen, Sulfur, and Nitrogen Nucleophiles to Maleimides Catalyzed by BF3·OEt2.
Authors: An Yu‐Long , Deng Yun‐Xia , Zhang Wei , Zhao Sheng‐Yin
Published: September 2015

The addition of oxygen, nitrogen, and sulfur nucleophiles to maleimides catalyzed by boron trifluoride etherate is studied.
Abundance of phosphorylated Apis mellifera CREB in the honeybee's mushroom body inner compact cells varies with age
Authors: Gehring Katrin B. , Heufelder Karin , Kersting Isabella , Eisenhardt Dorothea
Published: September 2015

Hymenopteran eusociality has been proposed to be associated with the activity of the transcription factor CREB (cAMP‐response element binding protein). The honeybee (Apis mellifera) is a eusocial insect displaying a pronounced age‐dependent division of labor. In honeybee brains, CREB‐dependent genes are regulated in an age‐dependent manner, indicating that there might be a role for neuronal honeybee CREB (Apis mellifera CREB, or AmCREB) in the bee's division of labor. In this study, we further explore this hypothesis by asking where in the honeybee brain AmCREB‐dependent processes might take place and whether they vary with age in these brain regions. CREB is activated following phosphorylation at a conserved serine residue. An increase of phosphorylated CREB is therefore regarded as an indicator of CREB‐dependent transcriptional activation. Thus, we here examine the localization of phosphorylated AmCREB (pAmCREB) in the brain and its age‐dependent variability. We report prominent pAmCREB staining in a subpopulation of intrinsic neurons of the mushroom bodies. In these neurons, the inner compact cells (IC), pAmCREB is located in the nuclei, axons, and dendrites. In the central bee brain, the IC somata and their dendritic region, we observed an age‐dependent increase of pAmCREB.

Our results demonstrate the IC to be candidate neurons involved in age‐dependent division of labor. We hypothesize that the IC display a high level of CREB‐dependent transcription that might be related to neuronal and behavioral plasticity underlying a bee's foraging behavior. J. Comp. Neurol. 524:1165–1180, 2016. © 2015 Wiley Periodicals, Inc.
Repeated game theory as a framework for algorithm development in communication networks
Authors: Coimbra J. , Correia N.
Published: September 2015

This article presents a tutorial on how to use repeated game theory as a framework for algorithm development in communication networks. The article starts by introducing the basis of one‐stage games and how the outcome of such games can be predicted, through iterative elimination and Nash equilibrium. In communication networks, however, not all problems can be modeled using one‐stage games. Some problems can be better modeled through multi‐stage games, as many problems in communication networks consist of several iterations or decisions that need to be made over time. Of all the multi‐stage games, the infinite‐horizon repeated games were chosen to be the focus in this tutorial, because optimal equilibrium settings can be achieved, contrarily to the suboptimal equilibria achieved in other types of game. With the theoretical concepts introduced, it is then shown how the developed game theoretical model, and devised equilibrium, can be used as a basis for the behavior of an algorithm, which is supposed to solve a particular problem and will be running at specific network devices. Copyright © 2015 John Wiley & Sons, Ltd.
Joint channel and sink assignment for data collection in cognitive wireless sensor networks
Authors: Wang Xinglong , Huang Liusheng , Leng Bing , Xu Hongli , Yang Chenkai
Published: September 2015

Data collection is a fundamental operation in cognitive wireless sensor networks (CWSNs). However, previous works on data collection assume that a node can transmit data to any node within its transmission range, which is not reasonable in CWSNs. To ensure that the previous works can be applied in CWSNs, this paper focuses on the joint channel and sink assignment problem, which is a critical preparatory work for data collection in CWSNs. Because the capacity performance of a CWSN is usually considered as a key problem in fundamental understanding, we are interested in finding a joint channel and sink assignment for each sensor node, such that the minimum capacity of all sensor nodes is maximized. We formulate our problem as a mixed integer linear program by some elaborate mathematical skills. Then, two algorithms based on greedy strategy and linear relaxation technique are proposed. Extensive simulations results show that our algorithms are efficient and able to achieve near‐optimal performance. Copyright © 2015 John Wiley & Sons, Ltd.
Indirect photochemical transformations of acyclovir and penciclovir in aquatic environments increase ecological risk
Authors: An Jibin , Li Guiying , An Taicheng , Nie Xiangping
Published: September 2015

Acyclovir and penciclovir, 2 antiviral drugs, are increasingly detected in aquatic environments. The present study explores the natural photochemical transformation mechanisms and fate of these drugs, examining direct and indirect photochemical transformation under simulated sunlight irradiation. The 2 antiviral drugs are photostable under certain conditions but significantly degrade in the presence of chromophoric dissolved organic matter (DOM). The degradation rate associated with the drugs' indirect photochemical transformation scaled with chromophoric DOM concentration. Quenchers and sensitizers were used to identify indirect photochemical transformation mechanism. Results suggested that both pharmaceuticals could be transformed by reacting with 1O2, •OH, and excited chromophoric DOM. The 1O2 played an important role in indirect photochemical transformation. Furthermore, the reaction kinetics between their substructural molecules, guanine, isocytosine, and imidazole, with different reactive oxygen species were evaluated to determine which substrate functionalities were most susceptible to singlet oxygenation. Imidazole was identified as the reaction site for 1O2, and preliminary 1O2 oxidation mechanisms were further evaluated based on liquid chromatographic–tandem mass spectrometric results. Finally, aquatic ecotoxicity assessment of phototransformed solutions revealed that the degradation of acyclovir and penciclovir may not ultimately diminish environmental risk because of either formation of more toxic intermediates than parent pharmaceuticals or some synergistic effects existing between the intermediates. Environ Toxicol Chem 2016;35:584–592. © 2015 SETAC
Fusion of PDGFRB to MPRIP, CPSF6, and GOLGB1 in three patients with eosinophilia‐associated myeloproliferative neoplasms
Authors: Naumann Nicole , Schwaab Juliana , Metzgeroth Georgia , Jawhar Mohamad , Haferlach Claudia , Göhring Gudrun , Schlegelberger Brigitte , Dietz Christian T. , Schnittger Susanne , Lotfi Sina , Gärtner Michael , Dang Tu‐Anh , Hofmann Wolf‐Karsten , Cross Nicholas C. P. , Reiter Andreas , Fabarius Alice
Published: September 2015

In eosinophilia‐associated myeloproliferative neoplasms (MPN‐eo), constitutive activation of protein tyrosine kinases (TK) as consequence of translocations, inversions, or insertions and creation of TK fusion genes is recurrently observed. The most commonly involved TK and their potential TK inhibitors include PDGFRA at 4q12 or PDGFRB at 5q33 (imatinib), FGFR1 at 8p11 (ponatinib), and JAK2 at 9p24 (ruxolitinib). We here report the identification of three new PDGFRB fusion genes in three male MPN‐eo patients: MPRIP‐PDGFRB in a case with t(5;17)(q33;p11), CPSF6‐PDGFRB in a case with t(5;12)(q33;q15), and GOLGB1‐PDGFRB in a case with t(3;5)(q13;q33). The fusion proteins identified by 5′‐rapid amplification of cDNA ends polymerase chain reaction (PCR) or DNA‐based long distance inverse PCR are predicted to contain the TK domain of PDGFRB. The partner genes contain domains like coiled‐coil structures, which are likely to cause dimerization and activation of the TK. In all patients, imatinib induced rapid and durable complete remissions. © 2015 Wiley Periodicals, Inc.
Coamplification of Myc/Pvt1 and homozygous deletion of Nlrp1 locus are frequent genetics changes in mouse osteosarcoma
Authors: Rao Pulivarthi H. , Zhao Shuying , Zhao Yi‐Jue , Yu Alexander , Rainusso Nino , Trucco Matteo , Allen‐Rhoades Wendy , Satterfield Laura , Fuja Daniel , Borra Vishnupriya J. , Man Tsz‐Kwong , Donehower Lawrence A. , Yustein Jason T.
Published: September 2015

Osteosarcomas (OSs) are characterized by high levels of genomic instability (GI). To gain insights into the GI and its contribution toward understanding the genetic basis of OS, we characterized 19 primary and 13 metastatic mouse tumors in a genetically engineered novel mouse model of OS by a combination of genomic techniques. Through the bone‐specific deletion of the wild‐type Trp53 locus or activation of a metastatic‐promoting missense R172Hp53 allele, C57BL/6 mice developed either localized or metastatic OS. Subsequent tumors were isolated and primary cultures created from primary bone and/or distal metastatic lesions, for example, lung and liver. These tumors exhibited high levels of GI with complex chromosomal rearrangements, amplifications, and deletions comparable to human OS. The combined genomic approaches identified frequent amplification of chromosome 15D1 and loss of 11B4 by CGH and/or SKY. Both 15D1 and 11B4 have homology with frequently altered chromosomal bands 8q24 and 17p13 in human OS, respectively. Subsequent array CGH, FISH, and qRT‐PCR analysis identified coamplification and overexpression of Myc/Pvt1 transcripts from the 15D1 amplicon and loss and decreased expression of the Nlrp1b from 11B4. The Nlrp1 gene is the key mediator of apoptosis and interacts strongly with caspase 2. © 2015 Wiley Periodicals, Inc.
Frequency of del(12p) is commonly underestimated in myelodysplastic syndromes: Results from a German diagnostic study in comparison with an international control group
Authors: Braulke Friederike , Müller‐Thomas Catharina , Götze Katharina , Platzbecker Uwe , Germing Ulrich , Hofmann Wolf‐Karsten , Giagounidis Aristoteles A. N. , Lübbert Michael , Greenberg Peter L. , Bennett John M. , Solé Francesc , Slovak Marilyn L. , Ohyashiki Kazuma , Le Beau Michelle M. , Tüchler Heinz , Pfeilstöcker Michael , Hildebrandt Barbara , Aul Carlo , Stauder Reinhard , Valent Peter , Fonatsch Christa , Bacher Ulrike , Trümper Lorenz , Haase Detlef , Schanz Julie
Published: September 2015

In myelodysplastic syndromes (MDS), deletion of the short arm of chromosome 12 (del(12p)) is usually a small abnormality, rarely detected as a single aberration by chromosome banding analysis (CBA) of bone marrow metaphases. Del(12p) has been described in 0.6 to 5% of MDS patients at initial diagnosis and is associated with a good to intermediate prognosis as a sole anomaly according to current scoring systems. Here, we present the results of a systematic del(12p) testing in a German prospective diagnostic study (clinicaltrials.gov: NCT01355913) on 367 MDS patients in whom CD34+ peripheral blood cells were analysed for the presence of del(12p) by sequential fluorescence in situ hybridization (FISH) analyses. A cohort of 2,902 previously published MDS patients diagnosed by CBA served as control. We demonstrate that, using a sensitive FISH technique, 12p deletion occurs significantly more frequently in MDS than previously described (7.6% by CD34+ PB‐FISH vs. 1.6% by CBA, P < 0.001) and is often associated with other aberrations (93% by CD34+ PB‐FISH vs. 60% by CBA). Additionally, the detection rate can be increased by repeated analyses in a patient over time which is important for the patient´s prognosis to distinguish a sole anomaly from double or complex aberrations. To our knowledge, this is the first study to screen for 12p deletions with a suitable probe for ETV6/TEL in 12p13. Our data suggest that the supplement of a probe for the detection of a 12p deletion to common FISH probe panels helps to avoid missing a del(12p), especially as part of more complex aberrations. © 2015 Wiley Periodicals, Inc.
Potential resource and toxicity impacts from metals in waste electronic devices
Authors: Woo Seung H , Lee Dae Sung , Lim Seong-Rin
Published: September 2015

As a result of the continuous release of new electronic devices, existing electronic devices are quickly made obsolete and rapidly become electronic waste (e-waste). Because e-waste contains a variety of metals, information about those metals with the potential for substantial environmental impact should be provided to manufacturers, recyclers, and disposers to proactively reduce this impact. This study assesses the resource and toxicity (i.e., cancer, noncancer, and ecotoxicity) potentials of various heavy metals commonly found in e-waste from laptop computers, liquid-crystal display (LCD) monitors, LCD TVs, plasma TVs, color cathode ray tube (CRT) TVs, and cell phones and then evaluates such potentials using life cycle impact–based methods. Resource potentials derive primarily from Cu, Sb, Ag, and Pb. Toxicity potentials derive primarily from Pb, Ni, and Hg for cancer toxicity; from Pb, Hg, Zn, and As for noncancer toxicity; and from Cu, Pb, Hg, and Zn for ecotoxicity. Therefore, managing these heavy metals should be a high priority in the design, recycling, and disposal stages of electronic devices. Integr Environ Assess Manag 2016;12:364–370. © 2015 SETAC

Key Points

This study provides comprehensive information related with resource and toxicity potentials from heavy metals in waste consumer electronic devices. We have identified principal heavy metals that have significant economic and environmental impact potentials. This study can contribute to developing the sustainable design of consumer electronic devices to reduce potential environmental impacts from electronic waste.
Adult weight gain and risk of prostate cancer: A dose–response meta‐analysis of observational studies
Authors: Chen Qi , Chen Tao , Shi Wentao , Zhang Tianyi , Zhang Wei , Jin Zhichao , Wei Xin , Liu Yuzhou , He Jia
Published: September 2015

The association between adult weight gain and risk of prostate cancer has not been widely studied and the findings are inconsistent. Therefore, our study aimed to investigate the association between adult weight gain and risk of prostate cancer. PubMed, Embase and Web of Science databases were searched for relevant studies published before September 2014 using terms related to weight gain and prostate cancer. Summary estimates were obtained using the random‐effects model. Dose–response meta‐analysis, sensitivity analysis and publication bias tests were performed. Nine studies involving 497,634 participants and 22,338 cancer cases were included. For total prostate cancer, a positive relationship with adult weight gain was observed until weight gain increased to >30 kg. For low‐intermediate‐risk prostate cancer, a positive relationship with adult weight gain was observed until weight gain increased to >15 kg. For high‐risk prostate cancer, we observed a positive linear relationship with adult weight gain with a relative risk (RR) of 1.02 [95% confidence interval (CI) 1.00–1.04] for every 5‐kg increase. For fatal prostate cancer, we observed a positive linear relationship with adult weight gain with an RR of 1.12 (95% CI: 1.05–1.19) for every 5‐kg increase. There is evidence that adult weight gain is associated with an increased risk of high‐risk and fatal prostate cancer, but only low weight gain is positively associated with low‐intermediate‐risk prostate cancer.
Protective effects of sustained transscleral unoprostone delivery against retinal degeneration in S334ter rhodopsin mutant rats
Authors: Nagai Nobuhiro , Iwata Satoru , Kaji Hirokazu , Sampei Kaori , Katsukura Yuki , Onami Hideyuki , Nishizawa Matsuhiko , Nakazawa Toru , Mashima Yukihiko , Abe Toshiaki
Published: September 2015

It has been suggested that unoprostone isopropyl (UNO) has potent neuroprotective activity in the retina. The effect of sustained transscleral UNO delivery to the posterior segment of the eye on photoreceptor degeneration was evaluated. UNO was loaded into a device made of poly(ethyleneglycol) dimethacrylate by polydimethylsiloxane mold‐based UV‐curing. The amount of UNO diffusing from these devices was measured using high‐performance liquid chromatography. The polymeric devices that released UNO at 1.8 μg/day were implanted on the sclerae of S334ter rats at postnatal 21 days, and electroretinograms (ERGs) were compared with those of topical application and placebo devices. Retinal thickness was evaluated by histological examination. Western blots of specimens 4 weeks after implantation were performed. ERGs showed that the UNO‐loaded device prevented the reduction of ERG amplitudes 2 and 4 weeks after implantation, compared with results using a placebo device or topical application. Histological examination showed that the UNO‐loaded device prevented the reduction of retinal thickness, and Western blots of specimens indicated that the UNO‐loaded device decreased expression of ERK1/2, phosphorylated ERK1/2, and caspase‐3. A device that provided sustained UNO administration protected against retinal degeneration in rhodopsin mutant rats, and thus, may have translational potential as a sustainable method to administer drugs to treat retinitis pigmentosa. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1730–1737, 2016.