bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbon Nanotube‐Encapsulated Noble Metal Nanoparticle Hybrid as a Cathode Material for Li‐Oxygen Batteries
Authors: Huang Xin , Yu Hong , Tan Huiteng , Zhu Jixin , Zhang Wenyu , Wang Chengyuan , Zhang Jun , Wang Yuxi , Lv Yunbo , Zeng Zhi , Liu Dayong , Ding Jun , Zhang Qichun , Srinivasan Madhavi , Ajayan Pulickel M. , Hng Huey Hoon , Yan Qingyu
Published: August 2014

Although Li‐oxygen batteries offer extremely high theoretical specific energy, their practical application still faces critical challenges. One of the main obstacles is the high charge overpotential caused by sluggish kinetics of charge transfer that is closely related to the morphology of discharge products and their distribution on the cathode. Here, a series of noble metal nanoparticles (Pd, Pt, Ru and Au) are encapsulated inside end‐opened carbon nanotubes (CNTs) by wet impregnation followed by thermal annealing. The resultant cathode materials exhibit a dramatic reduction of charge overpotentials compared to their counterparts with nanoparticles supported on CNT surface. Notably, the charge overpotential can be as low as 0.3 V when CNT‐encapsulated Pd nanoparticles are used on the cathode. The cathode also shows good stability during discharge–charge cycling. Density functional theory (DFT) calculations reveal that encapsulation of “guest” noble metal nanoparticles in “host” CNTs is able to strengthen the electron density on CNT surfaces, and to avoid the regional enrichment of electron density caused by the direct exposure of nanoparticles on CNT surface. These unique properties ensure the uniform coverage of Li2O2 nanocrystals on CNT surfaces instead of localized distribution of Li2O2 aggregation, thus providing efficient charge transfer for the decomposition of Li2O2.
Inkjet Printing of MoS2
Authors: Li Jiantong , Naiini Maziar M. , Vaziri Sam , Lemme Max C. , Östling Mikael
Published: August 2014

A simple and efficient inkjet printing technology is developed for molybdenum disulfide (MoS2), one of the most attractive two‐dimensional layered materials. The technology effectively addresses critical issues associated with normal MoS2 liquid dispersions (such as incompatible rheology, low concentration, and solvent toxicity), and hence can directly and reliably write uniform patterns of high‐quality (5–7 nm thick) MoS2 nanosheets at a resolution of tens of micrometers. The technology efficiency facilitates the integration of printed MoS2 patterns with other components (such as electrodes), and hence allows fabricating various functional devices, including thin film transistors, photoluminescence patterns, and photodetectors, in a simple, massive and cost‐effective manner while retains the unique properties of MoS2. The technology has great potential in a variety of applications, such as photonics, optoelectronics, sensors, and energy storage.
Gradual Controlling the Work Function of Metal Electrodes by Solution‐Processed Mixed Interlayers for Ambipolar Polymer Field‐Effect Transistors and Circuits
Authors: Long Dang Xuan , Baeg Kang‐Jun , Xu Yong , Kang Seok‐Ju , Kim Myung‐Gil , Lee Geon‐Woong , Noh Yong‐Young
Published: August 2014

In this paper, a technique using mixed transition‐metal oxides as contact interlayers to modulate both the electron‐ and hole‐injections in ambipolar organic field‐effect transistors (OFETs) is presented. The cesium carbonate (Cs2CO3) and vanadium pentoixide (V2O5) are found to greatly and independently improve the charge injection properties for electrons and holes in the ambipolar OFETs using organic semiconductor of diketopyrrolopyrrolethieno[3,2‐b]thiophene copolymer (DPPT‐TT) and contact electrodes of molybdenum (Mo). When Cs2CO3 and V2O5 are blended at various mixing ratios, they are observed to very finely and constantly regulate the Mo's work function from −4.2 eV to −4.8 eV, leading to high electron‐ and hole‐mobilities as high as 2.6 and 2.98 cm2 V−1 s−1, respectively. The most remarkable finding is that the device characteristics and device performance can be gradually controlled by adjusting the composition of mixed‐oxide interlayers, which is highly desired for such applications as complementary circuitry that requires well matched n‐channel and p‐channel device operations. Therefore, such simple interface engineering in conjunction with utilization of ambipolar semiconductors can truly enable the promising low‐cost and soft organic electronics for extensive applications.
Single Crystal Gallium Nitride Nanomembrane Photoconductor and Field Effect Transistor
Authors: Xiong Kanglin , Park Sung Hyun , Song Jie , Yuan Ge , Chen Danti , Leung Benjamin , Han Jung
Published: August 2014

Large‐area, free‐standing and single‐crystalline GaN nanomembranes are prepared by electrochemical etching from epitaxial layers. As‐prepared nanomembranes are highly resistive but can become electronically active upon optical excitation, with an excellent electron mobility. The interaction of excited carriers with surface states is investigated by intensity‐dependent photoconductivity gain and temperature‐dependent photocurrent decay. Normally off enhancement‐type GaN nanomembrane MOS transistors are demonstrated, suggesting that GaN could be used in flexible electronics for high power and high frequency applications.
High‐Performance Electrofluorochromic Devices Based on Electrochromism and Photoluminescence‐Active Novel Poly(4‐Cyanotriphenylamine)
Authors: Wu Jia‐Hao , Liou Guey‐Sheng
Published: August 2014

A novel electrochromism (EC) and photoluminescence (PL)‐active poly(4‐cyanotriphenylamine) (CN‐PTPA) is prepared by oxidative coupling polymerization from 4‐cyanotriphenylamine (CN‐TPA) using FeCl3 as an oxidant. The high‐performance electrofluorochromic (EFC) devices using CN‐PTPA thin film with photoluminescent quantum yield of 21.9% as active layer are readily fabricated and reveal the highest fluorescent contrast ratio (I
off/I
on) of 242 between the fluorescent (neutral) state and the non‐fluorescent (oxidized) state, rapid response time shorter than 0.4 s, and excellent EFC stability longer than 9000 s. Furthermore, by introducing viologen into electrolyte as a counter EC layer for charge balance, the resulting EFC device exhibits notable improvement in reducing oxidation potential (from 2.30 V to 1.55 V) and switching recovery time (from 78 to 38 s) with enhanced fluorescent contrast ratio during pulse on/off multi‐cyclic scanning. These results demonstrate that incorporation of the EC and PL‐active CN‐PTPA is a facile and feasible approach to prepare highly efficient EFC devices.
Monocyte‐Targeting Supramolecular Micellar Assemblies: A Molecular Diagnostic Tool for Atherosclerosis
Authors: Chung Eun Ji , Mlinar Laurie B. , Nord Kathryn , Sugimoto Matthew J. , Wonder Emily , Alenghat Francis J. , Fang Yun , Tirrell Matthew
Published: August 2014

Atherosclerosis is a multifactorial inflammatory disease that can progress silently for decades and result in myocardial infarction, stroke, and death. Diagnostic imaging technologies have made great strides to define the degree of atherosclerotic plaque burden through the severity of arterial stenosis. However, current technologies cannot differentiate more lethal “vulnerable plaques,” and are not sensitive enough for preventive medicine. Imaging early molecular markers and quantifying the extent of disease progression continues to be a major challenge in the field. To this end, monocyte‐targeting, peptide amphiphile micelles (PAMs) are engineered through the incorporation of the chemokine receptor CCR2‐binding motif of monocyte chemoattractant protein‐1 (MCP‐1) and MCP‐1 PAMs are evaluated preclinically as diagnostic tools for atherosclerosis. Monocyte‐targeting is desirable as the influx of monocytes is a marker of early lesions, accumulation of monocytes is linked to atherosclerosis progression, and rupture‐prone plaques have higher numbers of monocytes. MCP‐1 PAMs bind to monocytes in vitro, and MCP‐1 PAMs detect and discriminate between early‐ and late‐stage atherosclerotic aortas. Moreover, MCP‐1 PAMs are found to be eliminated via renal clearance and the mononuclear phagocyte system (MPS) without adverse side effects. Thus, MCP‐1 PAMs are a promising new class of diagnostic agents capable of monitoring the progression of atherosclerosis.
Nanoparticles Containing a Liver X Receptor Agonist Inhibit Inflammation and Atherosclerosis
Authors: Zhang Xue‐Qing , Even‐Or Orli , Xu Xiaoyang , van Rosmalen Mariska , Lim Lucas , Gadde Suresh , Farokhzad Omid C. , Fisher Edward A.
Published: August 2014

Liver X receptor (LXR) signaling pathways regulate lipid metabolism and inflammation, which has generated widespread interest in developing synthetic LXR agonists as potential therapeutics for the management of atherosclerosis. In this study, it is demonstrated that nanoparticles (NPs) containing the synthetic LXR agonist GW3965 (NP‐LXR) exert anti‐inflammatory effects and inhibit the development of atherosclerosis without causing hepatic steatosis. These NPs are engineered through self‐assembly of a biodegradable diblock poly(lactide‐co‐glycolide)‐b‐poly(ethylene glycol) (PLGA‐b‐PEG) copolymer. NP–LXR is significantly more effective than free GW3965 at inducing LXR‐target gene expression and suppressing inflammatory factors in macrophages in vitro and in vivo. Additionally, the NPs elicit negligible lipogenic gene stimulation in the liver. Using the Ldlr
−/− mouse model of atherosclerosis, abundant colocalization of fluorescently labeled NPs within plaque macrophages following systemic administration is seen. Notably, six intravenous injections of NP–LXR over 2 weeks markedly reduce the CD68‐positive cell (macrophage) content of plaques (by 50%) without increasing total cholesterol or triglycerides in the liver and plasma. Together, these findings identify GW3965‐encapsulated PLGA‐b‐PEG NPs as a promising nanotherapeutic approach to combat atherosclerosis, providing the benefits of LXR agonists without their adverse effects on hepatic and plasma lipid metabolism.
Dimethyl Sulfoxide Participating in Copper(I) Iodide‐Catalyzed Cascade Oxidation/Formylation Reactions: The Synthesis of α‐Formylpyrroles from 2,3‐Dihydro‐1H‐pyrroles
Authors: Qian Jingjing , Zhang Zhiguo , Liu Qingfeng , Liu Tongxin , Zhang Guisheng
Published: August 2014

An efficient copper‐catalyzed tandem oxidation/α‐formylation reaction of 2,3‐dihydro‐1H‐pyrroles in an oxygen atmosphere has been developed. The new reaction is conducted in dimethyl sulfoxide (DMSO), which serves as both the carbonyl carbon source and solvent, in the presence of trifluoroacetic acid to directly generate structurally diverse α‐formylpyrrole derivatives in one pot in moderate to good yields. Sensitive aldehyde groups remain intact in the presence of an oxidant, trifluoroacetic acid and a transition metal salt. A possible mechanism is presented.

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Cobalt‐Catalyzed Cross‐Coupling of Organozinc Halides with Bromoalkynes
Authors: Corpet Martin , Bai Xian‐Zhou , Gosmini Corinne
Published: August 2014

The cobalt‐catalyzed cross‐coupling of organozinc bromides is described. In the case of arylzinc reagents, the same cobalt catalyst, CoBr2(phen), can be used for both the synthesis of the organozinc species and the cross‐coupling reaction. In the case of alkylzinc halides, which allow access to dialkylalkynes, the method used for the preparation of the organozinc species has a significant impact on the yields.

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Silver‐Catalyzed Transformation of Propargylic Amine N‐Oxides to Enones and Acyloxy Ketones via Isoxazolinium Intermediates
Authors: Cui Jian‐Fang , Kung Karen Ka‐Yan , Ko Hok‐Ming , Hui Tsz‐Wai , Wong Man‐Kin
Published: August 2014

A novel silver‐catalyzed transformation of propargylic amine N‐oxides with switchable product profiles has been developed. A diversity of enones with excellent E/Z ratios (up to >20:1) were obtained when the reactions were conducted in aprotic solvents. In contrast, 3‐chlorobenzoxymethyl ketones and α‐(3‐chloro)‐benzoxy enones were obtained by using protic solvents. Mechanistic studies suggested that in situ generated isoxazolinium ions are the key intermediates involved in these novel silver‐catalyzed reaction pathways. Applications on the chemoselective modification of cysteine‐containing peptides in aqueous medium have also been achieved.

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Salivary cortisol and α‐amylase responses to repeated bouts of downhill running
Authors: Mckune Andrew J. , Bach Christopher W. , Semple Stuart J. , Dyer Barry J.
Published: August 2014

Objectives

To determine the hypothalamic‐pituitary‐adrenal (HPA) axis and sympathoadrenal (SA) system response to repeated bouts of downhill running.

Methods

Eleven active but untrained males (age: 19.7 ± 0.4 y; VO2peak 47.8 ± 3.6 ml/kg/min) performed two 60 min bouts of downhill running (−13.5% gradient), separated by 14 days, at a speed eliciting 75% of their VO2peak on a level grade. Saliva samples were collected before (baseline), after, and every hour for 12 h and every 24 h for 6 days after each run. Salivary cortisol and α‐amylase levels were measured as markers of the HPA axis and SA response, respectively. Results were analyzed using repeated measures ANOVA (12 h period: 2 × 14; 24 h intervals 2 × 7, P ≤ 0.05) with Tukey post‐hoc tests where appropriate. Paired samples t‐tests were used to compare collapsed data vs. baseline measurements.

Results

There were no significant group × time interactions for cortisol or α‐amylase for the hourly samples up to 12 h after each run, nor for the 24 h samples up to 6 days later. The 24 h samples for α‐amylase showed a significant group effect between runs (Run 1: 69.77 ± 7.68 vs. Run 2: 92.19 ± 7.67 U/ml; P = 0.04). Significant time effects were measured for both cortisol (decreased 2 h to 12 h post‐run) and α‐amylase (elevated immediately after, 1 h and 2 h post‐run) (P < 0.001).

Conclusion

The 24 h period group effect for salivary α‐amylase suggested an adaptation in the sympathoadrenal system that may alter the systemic inflammatory response to exercise‐induced muscle damage but may also reflect enhanced mucosal immunity. Am. J. Hum. Biol. 26:850–855, 2014. © 2014 Wiley Periodicals, Inc.
Synthese und Reaktion der ersten 1,2‐Oxaphosphetankomplexe
Authors: Kyri Andreas Wolfgang , Nesterov Vitaly , Schnakenburg Gregor , Streubel Rainer
Published: August 2014

Während PV‐1,2‐Oxaphosphetane von der Wittig‐Reaktion her geläufig sind, waren die PIII‐Analoga bisher unbekannt. Wir präsentieren hier die Synthese und Reaktionen der ersten 1,2‐Oxaphosphetankomplexe, die durch Reaktion des Phosphinidenoidkomplexes [Li(12‐Krone‐4)(Lsgm)][(OC)5W{(Me3Si)2HC‐PCl}] mit unterschiedlichen Epoxiden erhalten wurden. Die Titelverbindungen sind in Toluol bis ca. 100 °C stabil, bevor eine unselektive Zersetzung eintritt. Die säureinduzierte Ringerweiterung mit Benzonitril führt zur selektiven Bildung des ersten Komplexes mit einem 1,3,4‐Oxazaphosphacyclohex‐2‐en‐Liganden.
Cell‐Mediated Assembly of Phototherapeutics
Authors: Smith Weston J. , Oien Nathan P. , Hughes Robert M. , Marvin Christina M. , Rodgers Zachary L. , Lee Junghyun , Lawrence David S.
Published: August 2014

Light‐activatable drugs offer the promise of controlled release with exquisite temporal and spatial resolution. However, light‐sensitive prodrugs are typically converted to their active forms using short‐wavelength irradiation, which displays poor tissue penetrance. We report herein erythrocyte‐mediated assembly of long‐wavelength‐sensitive phototherapeutics. The activating wavelength of the constructs is readily preassigned by using fluorophores with the desired excitation wavelength λex. Drug release from the erythrocyte carrier was confirmed by standard analytical tools and by the expected biological consequences of the liberated drugs in cell culture: methotrexate, binding to intracellular dihydrofolate reductase; colchicine, inhibition of microtubule polymerization; dexamethasone, induced nuclear migration of the glucocorticoid receptor.
Incorporation of high oil content in polyvinyl acetate nanoparticles produced by batch miniemulsion polymerization stabilized with a polymeric stabilizer
Authors: Steinmacher Fernanda Regina , Araújo Pedro Henrique Hermes , Sayer Claudia
Published: August 2014

Nanoparticles (NPs) have been widely applied in the biomedical area. In order to satisfy the requirements for biomedical applications, sodium lauril sulfate (SLS) and hexadecane, widely used as anionic surfactant and co‐stabilizer, were successfully replaced by biocompatible compounds, in order to obtain poly(vinyl acetate) (PVAc) NPs via miniemulsion polymerization. The incorporation of high oil content in PVAc NPs was investigated, using different poly(vinyl alcohol) (PVOH) concentrations as polymeric surfactant. Besides the polymeric surfactant, lecithin and Miglyol 812, a triacylglycerol of saturated fatty acids obtained from coconut oil, were used as surfactant and co‐stabilizer, respectively. A high Miglyol 812 content was incorporated in the PVAc NPs and the morphology was investigated by TEM. The influence of PVOH concentration on the droplet nucleation mechanism and final morphology of PVAc NPs was evaluated. High PVOH concentration favored micellar particle nucleation. According to the TEM images, hemispheres nanoparticles were obtained. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 41365.
Association of FCGR3A and FCGR3B Copy Number Variations With Systemic Lupus Erythematosus and Rheumatoid Arthritis in Taiwanese Patients
Authors: Chen Ji‐Yih , Wang Chin‐Man , Chang Su‐Wei , Cheng Ching‐Hui , Wu Yeong‐Jian Jan , Lin Jing‐Chi , Yang Bing , Ho Huei‐Huang , Wu Jianming
Published: August 2014

Objective

To determine whether copy number variations (CNVs) in FCGR3A and FCGR3B are associated with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) in Taiwanese individuals.

Methods

FCGR3A and FCGR3B CNV genotypes were determined in 846 patients with SLE, 948 patients with RA, and 1,420 healthy control subjects, using custom TaqMan CNV assays. The FCGR3A and FCGR3B CNV genotypes were compared between healthy control subjects and patients and among patients stratified according to clinical characteristics.

Results

A low (<2) FCGR3A copy number was significantly associated with SLE (for <2 copies versus 2 copies, P = 5.06 × 10−4, false discovery rate–corrected P [PFDR] = 0.001, odds ratio [OR] 3.26, 95% confidence interval [95% CI] 1.68−6.35) and RA (for <2 copies versus 2 copies, P = 5.83 × 10−4, PFDR = 0.0012, OR 2.82, 95% CI 1.56−5.1). A low FCGR3B copy number was also significantly associated with SLE (for <2 copies versus 2 copies, P = 0.0032, PFDR = 0.0032, OR 1.59, 95% CI 1.17−2.18). Notably, a high (>2) FCGR3A copy number was also associated with SLE (for >2 copies versus 2 copies, P = 0.003, PFDR = 0.0061, OR 1.6, 95% CI 1.17−2.18). Additionally, the FCGR3A low copy number genotype was significantly enriched in subsets of patients with SLE (those with ulcer, arthritis, rash, discoid rash, photosensitivity, nephritis, leukopenia, thrombocytopenia, depressed complement levels, and autoantibody positivity) and patients with RA (those positive for rheumatoid factor) compared with healthy control subjects. The FCGR3B low copy number genotype was also significantly enriched in SLE patients with ulcer, rash, discoid rash, photosensitivity, ascites, nephritis, complement level depression, and anti–double‐stranded DNA antibody positivity compared with control subjects. However, FCGR3B CNVs were not associated with RA susceptibility (for <2 copy numbers versus 2 copy numbers, P = 0.3584, OR 1.15, 95% CI 0.85–1.55) and clinical characteristics.

Conclusion

In Taiwanese individuals, a low FCGR3A copy number is a common risk factor for SLE and RA, while a low FCGR3B copy number confers a risk of SLE but not RA.
Redox‐Mediated Angiogenesis in the Hypoxic Joint of Inflammatory Arthritis
Authors: Biniecka Monika , Connolly Mary , Gao Wei , Ng Chin T. , Balogh Emese , Gogarty Martina , Santos Lelani , Murphy Evelyn , Brayden David , Veale Douglas J. , Fearon Ursula
Published: August 2014

Objective

Inflammatory arthritis is associated with joint inflammation, synovial tissue proliferation, and degradation of articular cartilage and bone. Angiogenesis is an early and fundamental component of synovial inflammation. Oxygen metabolism is recognized as an important mediator of joint vascular remodeling. The aim of this study was to determine whether in vivo synovial hypoxia (tissue PO2 [tPO2]) and tumor necrosis factor (TNF) blocking therapy alter synovial vascular expression of NADPH oxidase (NOX) and how this action regulates angiogenic mechanisms.

Methods

NOX‐2 protein and messenger RNA expression was examined in patients with inflammatory arthritis before and after receiving TNF inhibitor (TNFi) therapy and in mice with collagen‐induced arthritis (CIA). Proangiogenic processes were assessed in human microvascular endothelial cells (HMVECs) following culture with NOX‐2 activators (TNFα and 4‐hydroxynonenal), small interfering RNA (siRNA) for NOX, and the inhibitor diphenyleneiodonium (DPI) under conditions of normoxia or 3% hypoxia.

Results

We demonstrated significantly increased NOX‐2 expression in the joints of patients with inflammatory arthritis and the joints of mice with CIA as compared to controls. NOX‐2 expression was higher in patients with synovial tPO2 levels <3% than in those with tPO2 levels >3% (P < 0.05), and correlated with in vivo macroscopic/microscopic measures of angiogenesis, such as vascularity and levels of vascular endothelial growth factor, angiopoietin 2, factor VIII, neural cell adhesion molecule, and α‐smooth muscle actin (P < 0.05 for all). A decrease in NOX‐2 expression was paralleled by an increase in in vivo tPO2levels only in those patients who were defined as TNFi responders. In vitro NOX‐2 activators and 3% hypoxia significantly promoted HMVEC migration, angiogenic tube formation, and secretion of proangiogenic mediators, effects that were blocked by siRNA for NOX‐2 or the NOX‐2 inhibitor DPI.

Conclusion

We demonstrated that hypoxia activates NOX‐2 protein expression, and NOX‐2–induced oxidative stress may be an initiating factor in driving angiogenesis.
Transcriptome‐Wide Analysis of Messenger RNA Decay in Normal and Osteoarthritic Human Articular Chondrocytes
Authors: Tew Simon R. , McDermott Benjamin T. , Fentem Rory B. , Peffers Mandy J. , Clegg Peter D.
Published: August 2014

Objective

Messenger RNA (mRNA) decay rates control not only gene expression levels, but also responsiveness to altered transcriptional input. We undertook this study to examine transcriptome‐wide posttranscriptional regulation in both normal and osteoarthritic (OA) human articular chondrocytes.

Methods

Human articular chondrocytes were isolated from normal or OA tissue. Equine articular chondrocytes were isolated from young or old horses at a commercial abattoir. RNA decay was measured across the transcriptome in human cells by microarray analysis following an actinomycin D chase. Messenger RNA levels in samples were confirmed using quantitative reverse transcription–polymerase chain reaction.

Results

Examination of total mRNA expression levels demonstrated significant differences in the expression of transcripts between normal and OA chondrocytes. Interestingly, almost no difference was observed in total mRNA expression between chondrocytes from intact OA cartilage and those from fibrillated OA cartilage. Decay analysis revealed a set of rapidly turned over transcripts associated with transcriptional control and programmed cell death that were common to all chondrocytes and contained binding sites for abundant cartilage microRNAs. Many transcripts exhibited altered mRNA half‐lives in human OA chondrocytes compared to normal cells. Specific transcripts whose decay rates were altered were generally less stable in these pathologic cells. Examination of selected genes in chondrocytes from young and old healthy horses did not identify any change in mRNA turnover.

Conclusion

This is the first investigation into the “posttranscriptome” of the chondrocyte. It identifies a set of short‐lived chondrocyte mRNAs likely to be highly responsive to altered transcriptional input as well as mRNAs whose decay rates are affected in OA chondrocytes.
Comparison of Outcomes in Adults With Pediatric‐Onset Morphea and Those With Adult‐Onset Morphea: A Cross‐Sectional Study From the Morphea in Adults and Children Cohort
Authors: Condie Daniel , Grabell Daniel , Jacobe Heidi
Published: August 2014

Objective

Few studies have examined outcomes in adults with pediatric‐onset morphea. The objective of the present study was to compare clinical outcomes and health‐related quality of life (HRQOL) in adults with onset of morphea in childhood to those in patients with adult onset of morphea.

Methods

Participants in the study were drawn from the Morphea in Adults and Children cohort and included 68 adults with pediatric‐onset morphea and 234 patients with adult‐onset morphea. Outcome measures included the Localized Scleroderma Cutaneous Assessment Tool (LoSCAT), physical examination findings, and HRQOL questionnaires.

Results

Adults with pediatric‐onset morphea were younger, had longer disease duration, and were more likely to have the linear subtype of morphea. Patients with pediatric‐onset disease were less likely to have active disease. Among patients with active disease, those with pediatric‐onset morphea had less disease activity as measured by the LoSCAT. Patients with pediatric‐onset disease had higher severity of disease damage when measured by the physician's global assessment of damage, but had similar levels of disease damage when measured by the Localized Scleroderma Skin Damage Index. Patients with pediatric‐onset disease had more favorable HRQOL scores for all measures, all of which were statistically significantly different from those in patients with adult‐onset morphea.

Conclusion

Adults with pediatric‐onset morphea differ from patients with adult‐onset disease with respect to disease subtype, severity of disease activity and damage, and levels of HRQOL.
Increased Frequency of a Unique Spleen Tyrosine Kinase Bright Memory B Cell Population in Systemic Lupus Erythematosus
Authors: Fleischer Sarah J. , Giesecke Claudia , Mei Henrik E. , Lipsky Peter E. , Daridon Capucine , Dörner Thomas
Published: August 2014

Objective

Systemic lupus erythematosus (SLE) is characterized by B cell hyperactivity and autoantibody production. As spleen tyrosine kinase (Syk) is pivotal in B cell activation, these experiments aimed to examine the extent to which Syk was abnormally expressed in SLE B cells and the nature of the B cell subset that differently expressed Syk.

Methods

B cells from healthy donors and SLE patients were analyzed by flow cytometry to assess basal expression of Syk and phosphorylated Syk. B cell subsets expressing higher levels of Syk were found, and their detailed phenotype, in vitro differentiation into plasmablasts/plasma cells, and Syk induction by cytokines were determined.

Results

Syk expression was higher in CD27+ memory B cells than in naive B cells from SLE patients. However, a significantly increased frequency of CD27− B cells with bright expression of Syk (Syk++) was found in SLE patients. CD27−Syk++ B cells showed enhanced basal expression of p‐Syk and stronger Syk phosphorylation upon B cell receptor (BCR) engagement as compared to CD27−Syk+ B cells. CD27−Syk++ B cells were CD38− as well as CD19++, CD20++, and mainly CD21−, with decreased ABCB1 transporter activity. In contrast to CD27−Syk+ B cells, CD27−Syk++ B cells exhibited enhanced differentiation into CD27++ IgG‐secreting cells and expressed somatically mutated BCR gene rearrangements. Syk++ B cells were inducible in vitro by stimulation with interferon‐γ, lipopolysaccharide, or tumor necrosis factor α.

Conclusion

SLE patients exhibit an increased frequency of hitherto unknown CD27−Syk++ memory‐like B cells, indicating that intracellular Syk density could distinguish CD27− memory B cells from truly naive B cell subsets. Furthermore, the CD27−Syk++ subset is a candidate for a source of increased plasma cells in SLE.
Necessary and Sufficient Near‐Optimal Conditions for Mean‐Field Singular Stochastic Controls
Authors: Li Ruijing , Liu Bin
Published: August 2014

We consider the near‐optimal control problems for mean‐field singular stochastic systems, where the control domain is non‐convex. By virtue of Ekeland's principle and some estimates on the state and adjoint processes, necessary and sufficient conditions for near‐optimality are established in the mean‐field framework. As an application, an example is presented to demonstrate the results.
Blocking endocytotic mechanisms to improve heterologous protein titers in Saccharomyces cerevisiae
Authors: Rodríguez‐Limas William A. , Tannenbaum Victoria , Tyo Keith E. J.
Published: August 2014

Saccharomyces cerevisiae is a useful platform for protein production of biopharmaceuticals and industrial enzymes. To date, substantial effort has focused on alleviating several bottlenecks in expression and the secretory pathway. Recently, it has been shown that highly active endocytosis could decrease the overall protein titer in the supernatant. In this study, we block endocytosis and trafficking to the vacuole using a modified TEV Protease‐Mediated Induction of Protein Instability (mTIPI) system to disrupt the endocytotic and vacuolar complexes. We report that conditional knock‐down of endocytosis gene Rvs161 improved the concentration of α‐amylase in supernatant of S. cerevisiae cultures by 63.7% compared to controls. By adaptive evolution, we obtained knock‐down mutants in Rvs161 and End3 genes with 2‐fold and 3‐fold α‐amylase concentrations compared to controls that were not evolved. Our study demonstrates that genetic blocking of endocytotic mechanisms can improve heterologous protein production in S. cerevisiae. This result is likely generalizable to other eukaryotic secretion hosts. Biotechnol. Bioeng. 2015;112: 376–385. © 2014 Wiley Periodicals, Inc.
Essential‐Oil Diversity of Salvia tomentosaMill. in Greece
Authors: Hanlidou Effie , Karousou Regina , Lazari Diamanto
Published: August 2014

Salvia tomentosa essential oils from Greece were studied for the first time here. The oils from five populations growing in Mediterranean pine forests on the island of Thassos (northern Aegean Sea) and from 14 populations situated in deciduous forests in Thrace (northeastern Greek mainland) were investigated. Their essential‐oil contents ranged from 1.1 to 3.3% (v/w, based on the dry weight of the plant material). The populations from Thassos had high contents of α‐pinene (18.0±2.9%), 1,8‐cineole (14.7±3.0%), cis‐thujone (14.0±6.9%), and borneol (12.8±2.2%) and smaller amounts of camphene, camphor, and β‐pinene, whereas the populations from Thrace showed high α‐pinene (16.7±4.0%), β‐pinene (22.8±4.5%), camphor (18.3±4.3%), and camphene (10.3±2.4%) contents, much lower 1,8‐cineole and borneol amounts, while cis‐thujone was completely lacking. The comparison of the present results with published data showed that oils having cis‐thujone as one of the main compounds were reported for the first time here. Multivariate statistical analyses indicate that the observed essential‐oil variation was related to geographical and environmental factors.
Cytotoxic and Nitric Oxide Production‐Inhibitory Activities of Limonoids and Other Compounds from the Leaves and Bark of Melia azedarach
Authors: Pan Xin , Matsumoto Masahiro , Nishimoto Yuki , Ogihara Eri , Zhang Jie , Ukiya Motohiko , Tokuda Harukuni , Koike Kazuo , Akihisa Momoko , Akihisa Toshihiro
Published: August 2014

Nine limonoids, 1–9, one apocarotenoid, 11, one alkaloid, 12, and one steroid, 13, from the leaf extract; and one triterpenoid, 10, five steroids, 14–18, and two flavonoids, 19 and 20, from the bark extract of Melia azedarach L. (Chinaberry tree; Meliaceae) were isolated. Among these compounds, three compounds, 4–6, were new, and their structures were established as 3‐deacetyl‐28‐oxosalannolactone, 3‐deacetyl‐28‐oxosalanninolide, and 3‐deacetyl‐17‐defurano‐17,28‐dioxosalannin, respectively, on the basis of extensive spectroscopic analyses and comparison with literature data. All of the isolated compounds were evaluated for their cytotoxic activities against leukemia (HL60), lung (A549), stomach (AZ521), and breast (SK‐BR‐3) cancer cell lines. 3‐Deacetyl‐4′‐demethyl‐28‐oxosalannin (3) against HL60 and AZ521 cells, and methyl kulonate (10) against HL60 cells exhibited potent cytotoxicities with IC50 values in the range of 2.8–5.8 μM. In addition, upon evaluation of compounds 1–13 against production of nitric oxide (NO) in mouse macrophage RAW 264.7 cells induced by lipopolysaccharide (LPS), seven, i.e., trichilinin B (1), 4, ohchinin (7), 23‐hydroxyohchininolide (8), 21‐hydroxyisoohchininolide (9), 10, and methyl indole 3‐carboxylate (12), inhibited production of NO with IC50 values in the range of 4.6–87.3 μM with no, or almost no, toxicity to the cells (IC50 93.2–100 μM). Western blot analysis revealed that compound 7 reduced the expression levels of the inducible NO synthase (iNOS) and COX‐2 proteins in a concentration‐dependent manner. Furthermore, compounds 5, 6, 13, and 18–20 exhibited potent inhibitory effects (IC50 299–381 molar ratio/32 pmol TPA) against EpsteinBarr virus early antigen (EBV‐EA) activation induced by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) in Raji cell line.
Synthesis of Cholesterol Analogues Bearing BODIPY Fluorophores by Suzuki or Liebeskind–Srogl Cross‐Coupling and Evaluation of Their Potential for Visualization of Cholesterol Pools
Authors: Liu Zheng , Thacker Seth G , Fernandez‐Castillejo Sara , Neufeld Edward B. , Remaley Alan T. , Bittman Robert
Published: August 2014

We report a synthetic route to BODIPY–cholesterol conjugates in which the key steps were Suzuki or Liebeskind–Srogl cross‐coupling of cholesterol phenyl moieties with structurally diverse BODIPY scaffolds. All conjugates feature single‐bonded and hydrophobic linkages between the fluorophore and sterol that are devoid of heteroatoms. Using HeLa cells, we show that these BODIPY–cholesterol analogues can be used simultaneously with the parent BODIPY–cholesterol for cell imaging and flow cytometry. The BODIPY–cholesterol analogues exhibit similar cellular localization in HeLa cells and show similar cholesterol efflux properties from THP‐1 cells to HDL acceptors. These results demonstrate that the red‐shifted BODIPY–cholesterol analogues behave in a manner similar to unlabeled cholesterol and are useful probes for simultaneous visualization of intracellular cholesterol pools and for monitoring cholesterol efflux from cells to extracellular acceptors.
Traceless Semisynthesis of a Set of Histone 3 Species Bearing Specific Lysine Methylation Marks
Authors: Chen Zhonglei , Grzybowski Adrian T. , Ruthenburg Alexander J.
Published: August 2014

Considerable mechanistic insight into the function of histone post‐translational modifications and the enzymes that install and remove them derives from in vitro experiments with modified histones, often embedded in nucleosomes. We report the first semisyntheses of native‐like histone 3 (H3) bearing tri‐ and dimethyllysines at position 79 and trimethyllysine at position 36, as well as more facile and traceless semisyntheses of K9 and K27 trimethylated species. These semisyntheses are practical on a multi‐milligram scale and can also generate H3 with combinations of marks. Each of these modifications has distinct functional consequences, although the pathways by which H3K36me3 and H3K79me2/3 act have not been entirely mapped. To this end, we demonstrated that our semisynthetic histones, when reconstituted into nucleosomes, are valuable affinity reagents for unbiased binding partner discovery and compare them to their methyllysine analogue (MLA) counterparts at the nucleosome level.
Synthesis and Characterization of Supported Cobalt–Manganese Nanoparticles as Model Catalysts for Fischer–Tropsch Synthesis
Authors: Werner Sebastian , Johnson Gregory R. , Bell Alexis T.
Published: August 2014

Supported Co is an effective catalyst for the Fischer–Tropsch synthesis of various hydrocarbon products that can be converted to diesel. Recent studies have shown that the formation of methane can be suppressed and the formation of C5+ products enhanced by promoting Co with Mn. Because the activity and product selectivity of Co‐based catalysts are dependent on the size of Co nanoparticles and the extent of Co promotion by Mn, it is desirable to understand these effects by investigating the performance of Co nanoparticles with well‐defined size and elemental composition. The present study was undertaken with the aim of producing well‐defined nanoparticles of Co and Co–Mn and then supporting them on silica. Co and Co–Mn particles were synthesized through the polyol reduction of Co and Mn acetylacetonates. By controlling synthesis conditions, Co particles with diameters of 7–10 nm and similarly sized Co–Mn (Mn/Co=0.1) particles were prepared. XRD and elemental mapping with scanning TEM‐energy‐dispersive X‐ray spectroscopy and scanning TEM‐electron energy loss spectroscopy studies suggested that most of the Mn species was associated with the Co particles. Ex situ prepared Co and Co–Mn nanoparticles were first supported on silica and then investigated for the catalytic activity for the Fischer–Tropsch synthesis. The turnover frequencies and product distributions obtained with silica‐supported Co and Co–Mn nanoparticles were similar to those obtained with catalysts prepared by using the conventional incipient wetness impregnation method. However, the rate of CO consumption per mass of Co was much lower for the catalysts produced by supporting ex situ prepared nanoparticles. This effect was attributed to the sintering of the nanoparticles during their calcination and reduction. Magnetic interactions among nanoparticles during their immobilization and thermal pretreatment were identified as the primary cause of sintering.
Stereoselective CH Borylations of Cyclopropanes and Cyclobutanes with Silica‐Supported Monophosphane–Ir Catalysts
Authors: Murakami Ryo , Tsunoda Kiyoshi , Iwai Tomohiro , Sawamura Masaya
Published: August 2014

Heteroatom‐directed CH borylation of cyclopropanes and cyclobutanes was achieved with silica‐supported monophosphane–Ir catalysts. Borylation occurred at the CH bonds located γ to the directing N or O atoms with exceptional cis stereoselectivity relative to the directing groups. This protocol was applied to the borylation of a tertiary CH bond of a ring‐fused cyclopropane.
Randomized phase 2 study of bone‐targeted therapy containing strontium‐89 in advanced castrate‐sensitive prostate cancer
Authors: Bilen Mehmet Asim , Johnson Marcella M. , Mathew Paul , Pagliaro Lance C. , Araujo John C. , Aparicio Ana , Corn Paul G. , Tannir Nizar M. , Wong Franklin C. , Fisch Michael J. , Logothetis Christopher J. , Tu Shi‐Ming
Published: August 2014

BACKGROUND

Radiopharmaceutical use may improve the survival time of patients with castrate‐resistant prostate cancer and bone metastases. Whether androgen‐deprivation therapy (ADT) combined with bone‐targeted therapy provides a clinical benefit to patients with advanced castrate‐sensitive prostate cancer has not been investigated.

METHODS

Eighty male patients were enrolled, and 79 were randomized: 40 to the control arm and 39 to the strontium‐89 (Sr‐89) arm. After randomization, patients in both study arms received ADT, doxorubicin, and zoledronic acid. Kaplan‐Meier methodology was used to evaluate the progression‐free survival (PFS) time. Multivariate Cox proportional hazards regression was used to evaluate the effects of Sr‐89 after controlling for the number of bone metastases.

RESULTS

The median follow‐up time for the 29 patients alive at the last follow‐up was 76.9 months (range, 0.07‐103.4 months). The median PFS time was 18.5 months (95% confidence interval, 9.7‐49.4 months) for the control arm and 12.9 months (95% confidence interval, 8.9‐72.5 months) for the Sr‐89 arm (P = .86). No patient developed myelodysplastic syndrome or a hematologic malignancy. An unplanned subgroup analysis suggested increased efficacy of bone‐targeted therapy with a greater extent of bone involvement (ie, >6 bone metastases vs ≤6 bone metastases on the bone scan).

CONCLUSIONS

The data showed that bone‐targeted therapy using 1 dose of Sr‐89 combined with chemohormonal ablation therapy did not favorably affect the PFS of patients with castrate‐sensitive prostate cancer. The combined therapy was feasible and safe. Whether such bone‐targeted therapy provides a favorable outcome for those patients with a greater tumor burden in the bone warrants further investigation. Cancer 2015;121:69–76. © 2014 American Cancer Society.
No evidence for induction or selection of mutant sodium channel expression in the copepod Acartia husdsonica challenged with the toxic dinoflagellate Alexandrium fundyense
Authors: Finiguerra Michael , Avery David E. , Dam Hans G.
Published: August 2014

Some species in the dinoflagellate genus Alexandrium spp. produce a suite of neurotoxins that block sodium channels, known as paralytic shellfish toxins (PST), which have deleterious effects on grazers. Populations of the ubiquitous copepod grazer Acartia hudsonica that have co‐occurred with toxic Alexandrium spp. are better adapted than naïve populations. The mechanism of adaptation is currently unknown. We hypothesized that a mutation in the sodium channel could account for the grazer adaptation. We tested two hypotheses: (1) Expression of the mutant sodium channel could be induced by exposure to toxic Alexandrium fundyense; (2) in the absence of induction, selection exerted by toxic A. fundyense would favor copepods that predominantly express the mutant isoform. In the copepod A. hudsonica, both isoforms are expressed in all individuals in varying proportions. Thus, in addition to comparing expression ratios of wild‐type to mutant isoforms for individual copepods, we also partitioned copepods into three groups: those that predominantly express the mutant (PMI) isoform, the wild‐type (PWI) isoform, or both isoforms approximately equally (EI). There were no differences in isoform expression between individuals that were fed toxic and nontoxic food after three and 6 days; induction of mutant isoform expression did not occur. Furthermore, the hypothesis that mutant isoform expression responds to toxic food was also rejected. That is, no consistent evidence showed that the wild‐type to mutant isoform ratios decreased, or that the relative proportion of PMI individuals increased, due to the consumption of toxic food over four generations. However, in the selected line that was continuously exposed to toxic food sources, egg production rate increased, which suggested that adaptation occurred but was unrelated to sodium channel isoform expression.
Analysis of rat testicular proteome following 30‐day exposure to 900 MHz electromagnetic field radiation
Authors: Sepehrimanesh Masood , Kazemipour Nasrin , Saeb Mehdi , Nazifi Saeed
Published: August 2014

The use of electromagnetic field (EMF) generating apparatuses such as cell phones is increasing, and has caused an interest in the investigations of its effects on human health. We analyzed proteome in preparations from the whole testis in adult male Sprague‐Dawley rats that were exposed to 900 MHz EMF radiation for 1, 2, or 4 h/day for 30 consecutive days, simulating a range of possible human cell phone use. Subjects were sacrificed immediately after the end of the experiment and testes fractions were solubilized and separated via high‐resolution 2D electrophoresis, and gel patterns were scanned, digitized, and processed. Thirteen proteins, which were found only in sham or in exposure groups, were identified by MALDI‐TOF/TOF‐MS. Among them, heat shock proteins, superoxide dismutase, peroxiredoxin‐1, and other proteins related to misfolding of proteins and/or stress were identified. These results demonstrate significant effects of radio frequency modulated EMFs exposure on proteome, particularly in protein species in the rodent testis, and suggest that a 30‐day exposure to EMF radiation induces nonthermal stress in testicular tissue. The functional implication of the identified proteins was discussed.
Assessment of cell viability after manipulation with insulator‐based dielectrophoresis
Authors: LaLonde Alexandra , Romero‐Creel Maria F. , Lapizco‐Encinas Blanca H.
Published: August 2014

The effects of insulator‐based DEP (iDEP) manipulation on cell viability were investigated by varying operating conditions and the shape of the insulating structures. Experiments were conducted with Escherichia coli, Bacillus subtilis, and Saccharomyces cerevisiae cells by varying the applied potential (300–1000 V), exposure time (1–4 min), and composition of the suspending medium (0–10% glucose); using devices made from polydimethylsiloxane. Cell viability was quantified employing Trypan blue staining protocols. The results illustrated a strong decrease in cell survival at higher applied electric potentials and exposure times; and an increase in cell viability obtained by increasing suspending medium osmolality. The composition and structure of the cell wall also played a major role on cell survival, where prokaryotic Gram‐positive B. subtilis was the most resilient cell strain, while eukaryotic S. cerevisiae had the lowest survival rate. Due to the popularity of iDEP in applications with biological cells, characterizing how iDEP operating conditions affect cell viability is essential.
International Legal: Detecting Foreign Corrupt Practices Crucial to Due Diligence in Acquisitions
Authors: Leibe Brandt
Published: August 2014

Due diligence in corporate transactions can be a major project undertaken with significant time constraints. Acquiring companies will ordinarily conduct detailed reviews of target companies' finances and contracts. Depending on the size and significance of the acquisition, there may be dozens of other issues delved into during the due diligence process. As part of this process, acquiring companies must not overlook an assessment of whether the target company has knowingly made corrupt payments to foreign officials to obtain or retain business that would constitute violations of the Foreign Corrupt Practices Act (FCPA).
Litigation—Environment: EPA Reinforces Standards to Use “Representative Data” After Sierra Club
Authors: Sanderson James W. , Lofland Samuel Lee
Published: August 2014

On January 22, 2013, in Sierra Club v. EPA, the US Court of Appeals for the District of Columbia issued an opinion that addressed some Prevention of Significant Deterioration (PSD) permitting program issues. Following this case, on March 4, 2013, the EPA issued guidance entitled “Draft Guidance for PM2.5 Permit Modeling,” and on May 20, 2014, issued its final “Guidance for PM2.5 Permit Modeling.” Sierra Club held that the Environmental Protection Agency lacked the legal authority to create an exemption to the PSD preconstruction data‐gathering requirement through the use of Significant Monitoring Concentrations (SMCs).
Natural Gas Matters: Gas‐Fired Generation and EPA's 111(d) Rules—Up to the Task?
Authors: Smead Richard G.
Published: August 2014

The Environmental Protection Agency's proposals to regulate carbon from existing power plants under Section 111(d) of the Clean Air Act are in the middle of their comment process, after being issued in June.
NERC and Enforcement Issues: NERC Provides New Definition of Bulk Electric System
Authors: Carpentier Deborah
Published: August 2014

Section 215 of the Federal Power Act (FPA) broadly defines the Bulk‐Power System (BPS) as “(A) facilities and control systems necessary for operating an interconnected electric energy transmission network (or any portion thereof); and (B) electric energy from generating facilities needed to maintain transmission system reliability.” Defining the extent of the BPS is important because the Federal Energy Regulatory Commission (FERC) requires each user, owner, and operator of the BPS to register with the North American Electric Reliability Corporation (NERC), and it is this registration that dictates the reliability standards with which the entity must comply.