bluuebunny/crossref_metadata_2025 huggingface dataset:
Potassium N‐Iodo p‐Toluenesulfonamide (TsNIK, Iodamine‐T): A New Reagent for the Oxidation of Hydrazones to Diazo Compounds
Authors: Nicolle Simon M. , Moody Christopher J.
Published: March 2014

A new reagent for the oxidation of hydrazones to diazo compounds is described. N‐Iodo p‐toluenesulfonamide (TsNIK, iodamine‐T) allows the preparation of α‐diazoesters, α‐diazoamides, α‐diazoketones and α‐diazophosphonates in good yield and in high purity after a simple extractive work‐up. α‐Diazoesters were also obtained in high yield from the corresponding ketones through a one‐pot process of hydrazone formation/oxidation.
Palladium‐Catalyzed Alkoxycarbonylation of Terminal Alkenes To Produce α,β‐Unsaturated Esters: The Key Role of Acetonitrile as a Ligand
Authors: Malkov Andrei V. , Derrien Nolwenn , Barłóg Maciej , Kočovský Pavel
Published: March 2014

A mild protocol has been developed for the PdII‐catalyzed alkoxycarbonylation of terminal olefins to produce α,β‐unsaturated esters with a wide range of substrates. Key features are the use of MeCN as solvent (and/or ligand) to control the reactivity of the intermediate Pd complexes and the combination of CO with O2, which facilitates the CuII‐mediated reoxidation of the Pd0 complex to PdII and prevents double carbonylation.
Biosorption of Chromium(VI) Ions by Deposits Produced from Chicken Feathers after Soluble Keratin Extraction
Authors: Gao Pin , Liu Zhenhong , Wu Xiaoqian , Cao Zhangjun , Zhuang Yuan , Sun Weimin , Xue Gang , Zhou Meihua
Published: March 2014

Keratin biosorbents were prepared by reprocessing the deposits produced from chicken feathers after soluble keratin extraction. Biosorption of Cr(VI) ions onto the obtained biosorbents from aqueous solution was studied. Experimental factors affecting biosorption process such as pH and initial concentration of Cr(VI) ions were investigated. Langmuir, Freundlich and Dubinin–Radushkevich (D–R) isotherm models were used to describe the biosorption process for Cr(VI) ions. The results showed that Langmuir model better fit the experimental data than the Freundlich and D–R models, and the maximum monolayer biosorption capacity for Cr(VI) ions was found to be 21.35 mg/g at pH 6, 200 mg/L initial concentration of Cr(VI) ions and 30°C. The free energy was calculated as 11.35 kJ/mol from the D–R model, indicating that the biosorption of Cr(VI) occurred chemically. This result was also confirmed by scanning electron microscopy and Fourier transform infrared regarding the changes in morphology and surface structure of the biosorbents before and after Cr(VI) biosorption. Overall, the deposits generated from chicken feathers after soluble keratin extraction, which currently treated as wastes, should be regarded as a favorable alternative for the removal of Cr(VI) ions from aqueous solution.
Time‐Dependent Diaryl Ether Inhibitors of InhA: Structure–Activity Relationship Studies of Enzyme Inhibition, Antibacterial Activity, and in vivo Efficacy
Authors: Pan Pan , Knudson Susan E. , Bommineni Gopal R. , Li Huei‐Jiun , Lai Cheng‐Tsung , Liu Nina , Garcia‐Diaz Miguel , Simmerling Carlos , Patil Sachindra S. , Slayden Richard A. , Tonge Peter J.
Published: March 2014

The diaryl ethers are a novel class of antituberculosis drug candidates that inhibit InhA, the enoyl‐ACP reductase involved in the fatty acid biosynthesis (FASII) pathway, and have antibacterial activity against both drug‐sensitive and drug‐resistant strains of Mycobacterium tuberculosis. In the present work, we demonstrate that two time‐dependent B‐ring modified diaryl ether InhA inhibitors have antibacterial activity in a mouse model of TB infection when delivered by intraperitoneal injection. We propose that the efficacy of these compounds is related to their residence time on the enzyme, and to identify structural features that modulate drug–target residence time in this system, we have explored the inhibition of InhA by a series of B‐ring modified analogues. Seven ortho‐substituted compounds were found to be time‐dependent inhibitors of InhA, where the slow step leading to the final enzyme–inhibitor complex (EI*) is thought to correlate with closure and ordering of the InhA substrate binding loop. A detailed mechanistic understanding of the molecular basis for residence time in this system will facilitate the development of InhA inhibitors with improved in vivo activity.
PRTX‐100 and methotrexate in patients with active rheumatoid arthritis: A Phase Ib randomized, double‐blind, placebo‐controlled, dose‐escalation study
Authors: Bernton Edward , Gannon William , Kramer William , Kranz Eduard
Published: March 2014

PRTX‐100 is a highly‐purified preparation of staphylococcal protein A (SpA), with immunologic activity in vitro and in animal models of immune‐mediated inflammation. Following single‐dose healthy volunteer studies of safety and pharmacokinetics (PK), a multicenter, double‐blind, placebo‐controlled, sequential dose‐escalation, repeated‐dose phase I trial was conducted in patients with active rheumatoid arthritis (RA) on methotrexate therapy. Patients were randomized to receive either weekly intravenous PRTX‐100 (0.15, 0.45, 0.90, or 1.50 µg/kg) or placebo for 4 weeks. Safety and disease activity were assessed over 16 weeks. Pharmacokinetic profiles were obtained after the first and fourth doses. The most common treatment‐related adverse events were nausea, muscle spasms, dizziness, flushing, fatigue, RA flare, and headache. No serious adverse events were considered related to PRTX‐100, and none occurred in the highest dose group. Geometric mean values for plasma Cmax (ng/mL) were 4.1, 15.7, 26.5, and 51.2 for doses of 0.15, 0.45, 0.90, and 1.5 µg/kg, respectively. Anti‐drug antibodies (ADAs) developed in most PRTX‐100 patients, but incidence and titer were not dose‐dependent. At the two highest doses, data suggest PRTX‐100 may have an effect on RA disease activity, even in patients with ADAs.
Theoretical Design of Multi‐Nitroxyl Organocatalysts with Enhanced Reactivity for Aerobic Oxidation
Authors: Chen Kexian , Jia Lu , Wang Congmin , Yao Jia , Chen Zhirong , Li Haoran
Published: March 2014

Higher catalytic performances of N,N′,N′′‐trihydroxyisocyanuric acid (THICA), N,N‐dihydroxypyromellitimide (NDHPI), and N‐hydroxynaphthalimide (NHNI) than that of N‐hydroxyphthalimide (NHPI) have been demonstrated recently in aerobic oxidation. Herein, the rational design of reactive multi‐nitroxyl organocatalysts has been addressed theoretically by using systematic analysis of some important properties and catalytic activities of yet‐to‐be‐synthesized catalysts. Our results show that 1) NHNI and its analogue, similar to THICA, unlike NHPI and others, are unsuitable for solvent‐ or mediator‐free catalysis due to their strong intramolecular hydrogen‐bonding interactions; 2) increasing the reactive hydroxyimide groups on the same aromatic ring, or doped N atoms or ionic‐pair groups onto the aromatic ring, can improve catalytic reactivity, whereas appropriate enlargement of conjugated aromatic systems results in unchanged activity; 3) the newly designed catalysts are more active than NHPI and NHNI and have catalytic activities comparable to NDHPI and THICA; 4) the ionic‐pair supported case is suggested to be a very active catalyst, even towards inert propane, and can be used as a novel model catalyst for further improvements. The present work will be helpful in designing reactive hydroxyimide organocatalysts.
Visualization of the Heterogeneity of Cerium Oxidation States in Single Pt/Ce2Zr2Ox Catalyst Particles by Nano‐XAFS
Authors: Ishiguro Nozomu , Uruga Tomoya , Sekizawa Oki , Tsuji Takuya , Suzuki Motohiro , Kawamura Naomi , Mizumaki Masaichiro , Nitta Kiyofumi , Yokoyama Toshihiko , Tada Mizuki
Published: March 2014

The cerium oxidation states in single catalyst particles of Pt/Ce2Zr2Ox (x=7 to 8) were investigated by spatially resolved nano X‐ray absorption fine structure (nano‐XAFS) using an X‐ray nanobeam. Differences in the distribution of the Ce oxidation states between Pt/Ce2Zr2Ox single particles of different oxygen compositions x were visualized in the obtained two‐dimensional X‐ray fluorescent (XRF) mapping images and the Ce LIII‐edge nano X‐ray absorption near‐edge structure (nano‐XANES) spectra.
Understanding the Photochemical Pathway of In Vitro Target Delivery of Aluminium Phthalocyanine: A Mechanistic Approach Using Radical Reaction Chemistry
Authors: Akpe Victor , Vernet Erik , Madu Christian , Obirai Joseph C. , Brismar Hjalmar
Published: March 2014

A classical dye, aluminium phthalocyanine (AlPc), is used to study the photochemical processes involved in the chromophore‐assisted laser inactivation technique. Both cell‐free and cell‐based systems are investigated by novel methods and radical reaction chemistry. Findings on the photochemical pathways in two models representing cell‐free and a cell‐based systems are reported. In the cell‐free system, the unsubstituted, free, fluorescence‐active photosensitiser AlPc recovers its fluorescence signal by means of phosphorescence through a reversible photobleaching process. In the cell‐based system, photoactivation of substituted AlPc conjugated to an antibody results in the loss of fluorescence signal at the area examined. Reinjection of the AlPc‐conjugated antibodies restores the fluorescence signal.
Direct Synthesis of Phenol from Benzene by PdVOx Nanoparticles Using Molecular Oxygen
Authors: Shang Sensen , Yang Hua , Li Jun , Chen Bo , Lv Ying , Gao Shuang
Published: March 2014

Novel PdVOx nanoparticles (NPs) prepared by a one‐pot hydrogenation method are reported. X‐ray diffraction, X‐ray photoelectron spectroscopy, transmission electron microscopy, and UV/Vis spectroscopy were performed to characterize the PdVOx NPs. The NPs catalyzed benzene directly to phenol in 5.2 % yield with more than 99 % selectivity using O2 as the sole oxidant.
Synthesis and Application of Carbonated Fatty Acid Esters from Carbon Dioxide Including a Life Cycle Analysis
Authors: Schäffner Benjamin , Blug Matthias , Kruse Daniela , Polyakov Mykola , Köckritz Angela , Martin Andreas , Rajagopalan Prasanna , Bentrup Ursula , Brückner Angelika , Jung Sebastian , Agar David , Rüngeler Bettina , Pfennig Andreas , Müller Karsten , Arlt Wolfgang , Woldt Benjamin , Graß Michael , Buchholz Stefan
Published: March 2014

Carbon dioxide can be used in various ways as a cheap C1 source. However, the utilization of CO2 requires energy or energy‐rich reagents, which leads to further emissions, and therefore, diminishes the CO2‐saving potential. Therefore, life cycle assessment (LCA) is required for each process that uses CO2 to provide valid data for CO2 savings. Carbon dioxide can be incorporated into epoxidized fatty acid esters to provide the corresponding carbonates. A robust catalytic process was developed based on simple halide salts in combination with a phase‐transfer catalyst. The CO2‐saving potential was determined by comparing the carbonates as a plasticizer with an established phthalate‐based plasticizer. Although CO2 savings of up to 80 % were achieved, most of the savings arose from indirect effects and not from CO2 utilization. Furthermore, other categories have been analyzed in the LCA. The use of biobased material has a variety of impacts on categories such as eutrophication and marine toxicity. Therefore, the benefits of biobased materials have to be evaluated carefully for each case. Finally, interesting properties as plasticizers were obtained with the carbonates. The volatility and water extraction could be improved relative to the epoxidized system.
Amphiphilic and Phase‐Separable Ionic Liquids for Biomass Processing
Authors: Holding Ashley J. , Heikkilä Mikko , Kilpeläinen Ilkka , King Alistair W. T.
Published: March 2014

One main limiting factor for the technoeconomics of future bioprocesses that use ionic liquids (ILs) is the recovery of the expensive and potentially toxic IL. We have demonstrated a new series of phase‐separable ionic liquids, based on the hydrophobic tetraalkylphosphonium cation ([PRRRR]+), that can dissolve lignin in the neat state but also hemicellulose and high‐purity cellulose in the form of their electrolyte solutions with dipolar aprotic solvents. For example, the IL trioctylmethylphosphonium acetate ([P8881][OAc]) was demonstrated to dissolve up to 19 wt % of microcrystalline cellulose (MCC) at 60 °C with the addition of 40 wt % of DMSO. It was found that the MCC saturation point is dependent on the molar ratio of DMSO and IL in solution. At the optimum saturation, a ∼1:1 molar ratio of [P8881][OAc] to anhydroglucose units is observed, which demonstrates highly efficient solvation. This is attributed to the positive contribution that these more amphiphilic cation–anion pairs provide, in the context of the Lindman hypothesis. This effective dissolution is further illustrated by solution‐state HSQC NMR spectroscopy on MCC. Finally, it is also demonstrated that these electrolytes are phase separable by the addition of aqueous solutions. The addition of 10 % NaOAc solution allows a near quantitative recovery of high‐purity [P8881][OAc]. However, increased volumes of aqueous solution reduced the recovery. The regenerated material was found to partially convert into the cellulose II crystalline polymorph.
Influence of Structural Variations in Push–Pull Zinc Porphyrins on Photovoltaic Performance of Dye‐Sensitized Solar Cells
Authors: Yi Chenyi , Giordano Fabrizio , Cevey‐Ha Ngoc‐Le , Tsao Hoi Nok , Zakeeruddin Shaik M. , Grätzel Michael
Published: March 2014

We designed and synthesized two new zinc porphyrin dyes for dye‐sensitized solar cells (DSCs). Subtle molecular structural variation in the dyes significantly influenced the performance of the DSC devices. By utilizing these dyes in combination with a cobalt‐based redox electrolyte using a photoanode made of mesoporous TiO2, we achieved a power conversion efficiency (PCE) of up to 12.0 % under AM 1.5 G (100 mW cm−2) simulated solar light. Moreover, we obtained a high PCE of 6.4 % for solid‐state dye‐sensitized solar cells by using 2,2′,7,7′‐tetrakis‐(N,N‐di‐p‐methoxyphenylamine)‐9,9′‐spirobifluorene as a hole‐transporting material.
Uncovering Cryptic Glycan Markers in Multiple Sclerosis (MS) and Experimental Autoimmune Encephalomyelitis (EAE)
Authors: Wang Denong , Bhat Roopa , Sobel Raymond A. , Huang Wei , Wang Lai‐Xi , Olsson Tomas , Steinman Lawrence
Published: March 2014

Preclinical Research

Using an integrated antigen microarray approach, we observed epitope‐spreading of autoantibody responses to a variety of antigenic structures in the cerebrospinal fluid (CSF) of patients with multiple sclerosis (MS) and in the serum of mice with experimental autoimmune encephalomyelitis (EAE). These included previously described protein‐ and lipid‐based antigenic targets and newly discovered autoimmunogenic sugar moieties, notably, autoantibodies specific for the oligomannoses in both MS patient CSF and the sera of mice with EAE. These glycans are often masked by other sugar moieties and belong to a class of cryptic autoantigens. We further determined that these targets are highly expressed on multiple cell types in MS and EAE lesions. Co‐immunization of SJL/J mice with a Man9‐KLH conjugate at the time of EAE induction elicited highly significant levels of anti‐Man9‐cluster autoantibodies. Nevertheless, this anti‐glycan autoantibody response was associated with a significantly reduced clinical severity of EAE. The potential of these cryptic glycan markers and targeting antibodies for diagnostic and therapeutic interventions of neurological disorders has yet to be explored.
Vertical transmission of fungal endophytes is widespread in forbs
Authors: Hodgson Susan , de Cates Catherine , Hodgson Joshua , Morley Neil J. , Sutton Brian C. , Gange Alan C.
Published: March 2014

To date, it has been thought that endophytic fungi in forbs infect the leaves of their hosts most commonly by air‐borne spores (termed “horizontal transmission”). Here, we show that vertical transmission from mother plant to offspring, via seeds, occurs in six forb species (Centaurea cyanus, C. nigra, Papaver rhoeas, Plantago lanceolata, Rumex acetosa, and Senecio vulgaris), suggesting that this may be a widespread phenomenon. Mature seeds were collected from field‐grown plants and endophytes isolated from these, and from subsequent cotyledons and true leaves of seedlings, grown in sterile conditions. Most seeds contain one species of fungus, although the identity of the endophyte differs between plant species. Strong evidence for vertical transmission was found for two endophyte species, Alternaria alternata and Cladosporium sphaerospermum. These fungi were recovered from within seeds, cotyledons, and true leaves, although the plant species they were associated with differed. Vertical transmission appears to be an imperfect process, and germination seems to present a bottleneck for fungal growth. We also found that A. alternata and C. sphaerospermum occur on, and within pollen grains, showing that endophyte transmission can be both within and between plant generations. Fungal growth with the pollen tube is likely to be the way in which endophytes enter the developing seed. The fact that true vertical transmission seems common suggests a more mutualistic association between these fungi and their hosts than has previously been thought, and possession of endophytes by seedling plants could have far‐reaching ecological consequences. Seedlings may have different growth rates and be better protected against herbivores and pathogens, dependent on the fungi that were present in the mother plant. This would represent a novel case of trans‐generational resistance in plants.
Immobilization of 1,5,7‐Triazabicyclo[4.4.0]dec‐5‐ene on Magnetic γ‐Fe2O3 Nanoparticles: A Highly Recyclable and Efficient Nanocatalyst for the Synthesis of Organic Carbonates
Authors: Wu Liqiang , Tian Shuanbao
Published: March 2014

1,5,7‐Triazabicyclo[4.4.0]dec‐5‐ene was immobilized on magnetic γ‐Fe2O3 nanoparticles as a magnetic nanocatalyst. The nanoparticle reagent was obtained with good loading levels and has been successfully used for the efficient and selective synthesis of organic carbonates by the direct condensation of alcohols and diethyl carbonate. The catalyst is quantitatively recovered by an external magnet and can be reused for six cycles with almost consistent activity.
{Cu2+–Co3+–Cu2+} and {Cu2+–Fe3+–Cu2+} Heterobimetallic Complexes and Their Catalytic Properties
Authors: Srivastava Sumit , Ali Afsar , Tyagi Adish , Gupta Rajeev
Published: March 2014

We report on the heterobimetallic complexes {Cu+–Co3+–Cu+} (3), {Cu+–Fe3+–Cu+} (4), {Cu2+–Co3+–Cu2+} (5), and {Cu2+–Fe3+–Cu2+} (6) and show their catalytic applications in the oxidation of hindered phenols and the oxidative coupling of terminal alkynes. The former reaction produces C–C‐coupled and dealkylated products, whereas the latter leads to the homo‐ and heterocoupling of terminal alkynes. The facile redox interconversion between Cu+ and Cu2+ for the secondary metal ions in these heterobimetallic complexes appears to be essential for the observed catalysis, and an important design aspect is better substrate accessibility and the use of molecular oxygen as the sole oxidant.
Electrochemical Biosensors for the Determination of Cardiovascular Markers: a Review
Authors: Pedrero María , Campuzano Susana , Pingarrón José M.
Published: March 2014

Nowadays there is a growing interest in the development of devices for the fast and reliable detection and quantification of biomarkers associated with cardiovascular diseases (CVDs). The main objective is not only an early diagnosis of these diseases but also predicting the risk that an individual can suffer CVD. Electrochemical biosensors can play a key role in the development of low cost, portable and rapid sensing platforms for this purpose. This review discusses critically the state of the art in the development, applications and potential suitability of electrochemical biosensors for the determination of cardiovascular biomarkers as well as the required characteristics that these sensors should fulfill to be finally accepted in the clinical community.
Application of surface complexation models to anion adsorption by natural materials
Authors: Goldberg Sabine
Published: March 2014

Various chemical models of ion adsorption are presented and discussed. Chemical models, such as surface complexation models, provide a molecular description of anion adsorption reactions using an equilibrium approach. Two such models, the constant capacitance model and the triple layer model, are described in the present study. Characteristics common to all the surface complexation models are equilibrium constant expressions, mass and charge balances, and surface activity coefficient electrostatic potential terms. Methods for determining parameter values for surface site density, capacitances, and surface complexation constants also are discussed. Spectroscopic experimental methods of establishing ion adsorption mechanisms include vibrational spectroscopy, nuclear magnetic resonance spectroscopy, electron spin resonance spectroscopy, X-ray absorption spectroscopy, and X-ray reflectivity. Experimental determinations of point of zero charge shifts and ionic strength dependence of adsorption results and molecular modeling calculations also can be used to deduce adsorption mechanisms. Applications of the surface complexation models to heterogeneous natural materials, such as soils, using the component additivity and the generalized composite approaches are described. Emphasis is on the generalized composite approach for predicting anion adsorption by soils. Continuing research is needed to develop consistent and realistic protocols for describing ion adsorption reactions on soil minerals and soils. The availability of standardized model parameter databases for use in chemical speciation–transport models is critical. Environ Toxicol Chem 2014;33:2172–2180. Published 2014 Wiley Periodicals Inc. on behalf of SETAC. This article is a US Government work and as such, is in the public domain in the United States.
Design and analysis of an angular‐segmented full‐mobility visible light communications receiver
Authors: Burton Andrew , Ghassemlooy Zabih , Rajbhandari Sujan , Liaw Shien‐Kuei
Published: March 2014

This paper presents the concept, design and analysis for a visible light communications receiver utilising the angular and spatial diversity in order to achieve full mobility and protection from signal blocking in a typical home/office environment. The proposed receiver uses seven sub‐receivers, each dedicated to an independent viewing angle and direction. Employing selection combining, the receiver with the strongest signal is used for the communications channel. Full performance evaluation and numerical analysis of the proposed system have been performed in MATLAB and compared to that of a single receiver. The received power, impulse response, corresponding signal‐to‐noise ratios and root‐mean‐square delay spread are also investigated. Copyright © 2014 John Wiley & Sons, Ltd.
Atypical presentation of Eagle syndrome with hypoglossal nerve palsy and Horner syndrome
Authors: Bensoussan Yael , Letourneau–Guillon Laurent , Ayad Tareck
Published: March 2014

Background

Many nerve injuries have been associated with Eagle syndrome. The cranial nerves V, VII, IX, and X have been reported to be injured by the elongated styloid process in this syndrome.

Methods

We describe a case of Eagle syndrome with atypical symptoms of hypoglossal nerve palsy and Horner syndrome.

Results

A 56‐year‐old woman presented with right hypoglossal nerve palsy, right Horner syndrome, right neck pain, and symptoms mimicking transient cerebral ischemia. An angioscan showed elongated styloid process bilaterally with the right process compressing the right carotid artery causing a 75% stenosis. After an en bloc resection of the right styloid process, there were no further episodes of paresthesias. The neck pain completely disappeared, as well as the Horner syndrome. As for the hemitongue, the fasciculations disappeared but the atrophy remained.

Conclusion

This is the first Eagle syndrome case report describing a motor paralysis of a cranial nerve. © 2014 Wiley Periodicals, Inc. Head Neck 36: E136–E138, 2014
Acute prediction of laryngeal outcome during thyroid surgery by electromyographic laryngeal monitoring
Authors: Pavier Yoann , Saroul Nicolas , Pereira Bruno , Tauveron Igor , Gilain Laurent , Mom Thierry
Published: March 2014

Background

The purpose of this study was to evaluate the contribution of laryngeal intraoperative nerve monitoring (IONM) during thyroidectomy in predicting postoperative laryngeal mobility.

Methods

Between 2009 and 2012, 127 patients underwent thyroidectomy, during which 216 recurrent laryngeal nerves were stimulated with suprathreshold stimulations. Laryngeal mobility was examined through direct laryngoscopy. Statistical analysis was performed to determine specificity, sensitivity, negative predictive value (NPV), positive predictive value (PPV), and a threshold value in order to define a intraoperative diagnostic test.

Results

Nine patients had a unilateral laryngeal palsy. No bilateral laryngeal palsy was observed. The threshold value to assure the postoperative laryngeal mobility is 280 μV. For this value, specificity was 94.06%, sensitivity 100%, NPV 100%, and PPV 47.83%.

Conclusion

Laryngeal IONM can predict a favorable outcome of laryngeal mobility in cases in which the response exceeds 280 μV. Under this value, the risk of palsy is about 50% suggesting a staged surgery. © 2014 Wiley Periodicals, Inc. Head Neck 37: 835–839, 2015
Angiotensin-II Type 1 Receptor-Mediated Janus Kinase 2 Activation Induces Liver Fibrosis
Authors: Granzow Michaela , Schierwagen Robert , Klein Sabine , Kowallick Benita , Huss Sebastian , Linhart Markus , Mazar Irela G. Reza , Görtzen Jan , Vogt Annabelle , Schildberg Frank A. , Gonzalez-Carmona Maria A. , Wojtalla Alexandra , Krämer Benjamin , Nattermann Jacob , Siegmund Sören V. , Werner Nikos , Fürst Dieter O. , Laleman Wim , Knolle Percy , Shah Vijay H. , Sauerbruch Tilman , Trebicka Jonel
Published: March 2014

Activation of the renin angiotensin system resulting in stimulation of angiotensin-II (AngII) type I receptor (AT1R) is an important factor in the development of liver fibrosis. Here, we investigated the role of Janus kinase 2 (JAK2) as a newly described intracellular effector of AT1R in mediating liver fibrosis. Fibrotic liver samples from rodents and humans were compared to respective controls. Transcription, protein expression, activation, and localization of JAK2 and downstream effectors were analyzed by real-time polymerase chain reaction, western blotting, immunohistochemistry, and confocal microscopy. Experimental fibrosis was induced by bile duct ligation (BDL), CCl4 intoxication, thioacetamide intoxication or continuous AngII infusion. JAK2 was inhibited by AG490.

In vitro

experiments were performed with primary rodent hepatic stellate cells (HSCs), Kupffer cells (KCs), and hepatocytes as well as primary human and human-derived LX2 cells. JAK2 expression and activity were increased in experimental rodent and human liver fibrosis, specifically in myofibroblastic HSCs. AT1R stimulation in wild-type animals led to activation of HSCs and fibrosis

in vivo

through phosphorylation of JAK2 and subsequent RhoA/Rho-kinase activation. These effects were prevented in AT1R−/− mice. Pharmacological inhibition of JAK2 attenuated liver fibrosis in rodent fibrosis models.

In vitro

, JAK2 and downstream effectors showed increased expression and activation in activated HSCs, when compared to quiescent HSCs, KCs, and hepatocytes isolated from rodents. In primary human and LX2 cells, AG490 blocked AngII-induced profibrotic gene expression. Overexpression of JAK2 led to increased profibrotic gene expression in LX2 cells, which was blocked by AG490.

Conclusion :

Our study substantiates the important cell-intrinsic role of JAK2 in HSCs for development of liver fibrosis. Inhibition of JAK2 might therefore offer a promising therapy for liver fibrosis. (Hepatology 2014;60:334–348)
Cardiovascular pharmacodynamics of donepezil hydrochloride on the PR and QT intervals in patients with dementia
Authors: Igeta Hirofumi , Suzuki Yutaro , Tajiri Misuzu , Someya Toshiyuki
Published: March 2014

Objective

Although several case reports suggested that donepezil hydrochloride can induce bradycardia or atrioventricular block, the details remain unclear. We implemented a study of the impact of donepezil hydrochloride administration on PR, RR, and QT intervals.

Methods

The subjects were 18 patients who were diagnosed with either dementia or cognitive disorder (DSM‐IV‐TR) and were hospitalized between January 2011 and December 2012. After hospitalization, they were treated with donepezil hydrochloride. Clinical parameters and electrocardiograms before and after the administration of donepezil hydrochloride were retrieved from the patients' medical records.

Results

After the administration of donepezil hydrochloride, the mean PR interval significantly increased from 177.3 ± 30.9 to 186.8 ± 38.4 ms (p < 0.001). And the mean RR interval also significantly increased from 850.3 ± 112.5 to 886.7 ± 136.4 ms (p = 0.014). The mean difference in the PR interval before and after the administration of donepezil hydrochloride was 9.5 ± 17.1 (range = −21.0–44.0) ms. The QT intervals were unaffected by the administration of donepezil hydrochloride.

Conclusions

Care should be taken when administering donepezil to patients with atrioventricular block, or patients taking other drugs that can prolong the PR interval. Copyright © 2014 John Wiley & Sons, Ltd.
An Overview of Interfacial Radiation Chemistry in Nuclear Technology
Authors: Jonsson Mats
Published: March 2014

Interfacial radiation chemistry is of key importance in nuclear technology because most materials in the vicinity of radioactive materials in nuclear power plants, reprocessing plants, and repositories for nuclear waste are exposed to ionizing radiation. Corrosion is a crucial issue for the long‐term performance and safety of these installations. Nevertheless, this field is still fairly undeveloped. In this paper, the current state of the art with particular focus on reactions between aqueous radiolysis products and metal or metal oxide surfaces is discussed. The general reactivity of hydrogen peroxide and the hydroxyl radical towards oxide surfaces is discussed on the basis of recent experimental results and DFT calculations. More specific discussions on radiation‐induced surface processes in a future geological repository for spent nuclear fuel are given as relevant examples. This includes radiation‐induced dissolution of spent nuclear fuel in contact with groundwater, radiation‐induced corrosion of copper, and radiation‐induced alterations of bentonite clay. Current knowledge gaps in these areas are highlighted.
Regression Discontinuity Applications with Rounding Errors in the Running Variable
Authors: Dong Yingying
Published: March 2014

Many empirical applications of regression discontinuity (RD) models use a running variable that is rounded and hence discrete, e.g. age in years, or birth weight in ounces. This paper shows that standard RD estimation using a rounded discrete running variable leads to inconsistent estimates of treatment effects, even when the true functional form relating the outcome and the running variable is known and is correctly specified. This paper provides simple formulas to correct for this discretization bias. The proposed approach does not require instrumental variables, but instead uses information regarding the distribution of rounding errors, which is easily obtained and often close to uniform. Bounds can be obtained without knowing the distribution of the rounding error. The proposed approach is applied to estimate the effect of Medicare on insurance coverage in the USA, and to investigate the retirement‐consumption puzzle in China, utilizing the Chinese mandatory retirement policy. Copyright © 2014 John Wiley & Sons, Ltd.
TWIST1 Expression in Breast Cancer Cells Facilitates Bone Metastasis Formation
Authors: Croset Martine , Goehrig Delphine , Frackowiak Agnieszka , Bonnelye Edith , Ansieau Stéphane , Puisieux Alain , Clézardin Philippe
Published: March 2014

The transcription factor TWIST1 induces epithelial-mesenchymal transition and/or escape to the oncogenic-induced failsafe program, facilitating the intravasation of breast cancer cells in the systemic circulation and their dissemination to the lungs. Its involvement in breast cancer bone metastasis is unknown. To address this question, human osteotropic MDA-MB-231/B02 breast cancer cells were stably transfected with a Tet-inducible vector encoding for TWIST1, whose expression was specifically repressed in the presence of doxycycline (dox). The intra-arterial inoculation of transfectants expressing TWIST1 in immunodeficient mice substantially increased the extent of osteolytic lesions in these animals, being 50% larger than that of animals bearing mock-transfected tumors, as determined by radiography. This difference was accompanied by a sharp reduction of the bone volume (indicating a higher bone destruction) and a twofold increase in the tumor volume compared with mice bearing mock-transfected tumors, as determined by histomorphometry. Importantly, the suppression of TWIST1 expression in MDA-MB-231/B02 cells in the presence of dox abolished the stimulatory effect of TWIST1 on bone metastasis formation in vivo. Additionally, examination of the bone marrow from untreated and dox-treated animals on day 7 after tumor cell inoculation, at which time there was no evidence of radiographic osteolytic lesions, revealed that the number of tumor cell colonies that were recovered from the bone marrow of untreated mice was dramatically increased compared with that of dox-fed animals. In vitro, TWIST1 expression promoted tumor cell invasion and enhanced microRNA 10b (miR-10b) expression, a proinvasive factor, but was dispensable for growth of tumor cells. In vivo, the repression of miR-10b substantially decreased the presence of TWIST1-expressing breast cancer cells in the bone marrow. Overall, these results establish that TWIST1 facilitates breast cancer bone metastasis formation through a mechanism dependent of miR-10b, which leads to increase tumor burden and bone destruction. © 2014 American Society for Bone and Mineral Research.
Overlapping and Continued Alendronate or Raloxifene Administration in Patients on Teriparatide: Effects on Areal and Volumetric Bone Mineral Density—The CONFORS Study
Authors: Muschitz Christian , Kocijan Roland , Fahrleitner-Pammer Astrid , Pavo Imre , Haschka Judith , Schima Wolfgang , Kapiotis Stylianos , Resch Heinrich
Published: March 2014

Nine month teriparatide (TPTD) monotherapy followed by co-administration of raloxifene (RAL) or alendronate (ALN) for another nine 9 months resulted in incremental bone mineral density (BMD) increase. The aim of this study was to investigate the effects of continued antiresorptive treatments for 12 months in the extension phase. Postmenopausal women (n = 125) with severe osteoporosis on ongoing TPTD treatment for 9 months were randomized into three open-label groups for another 9 months: ALN (70 mg/week, n = 41), RAL (60 mg/d, n = 37) in addition to TPTD or no additional medication (n = 47) except Ca and vitamin D. After discontinuation of TPTD the respective antiresorptives were continued for a further 12 months, while patients in the TPTD monotherapy group received Ca and vitamin D. Amino-terminal propeptide of type I procollagen (P1NP) and cross-linked C-telopeptide (CTX), areal and volumetric BMD at the lumbar spine (LS) and hip were assessed. ALN resulted in continued BMD increase in LS (4.3 ± 1.5%; mean ± SD), femoral neck (4.2 ± 1.6%) and total hip (4 ± 1.6%; p < 0.001 for all), while RAL was only effective at the LS (2.4 ± 1.7%, p < 0.001) but no changes at the femoral neck (0.4 ± 1.4%) or total hip (−0.8 ± 1.5%) were observed. Cortical bone only increased in the ALN group (femoral neck 6.7 ± 2.7% and −1.3 ± 2.5%; total hip 13.8 ± 2.9% and −2.3 ± 2.5% for ALN and RAL, p < 0.001 for all; respectively). Analyzing the entire 30 months of therapy, the ALN group revealed the largest BMD increase in all regions. Our results suggest that the addition of ALN to ongoing TPTD and continuing ALN after TPTD was stopped may be beneficial for patients in terms of areal and volumetric BMD increase. Further research is warranted to determine the optimal timing of the initiation of the combination treatment, the respective antiresorptive medication and the potential benefit of this BMD increase regarding fracture prevention. © 2014 American Society for Bone and Mineral Research
Ankylosing Spondylitis Is Associated With an Increased Risk of Vertebral and Nonvertebral Clinical Fractures: A Population-Based Cohort Study
Authors: Muñoz-Ortego Juan , Vestergaard Peter , Rubio Josep Blanch , Wordsworth Paul , Judge Andrew , Javaid M Kassim , Arden Nigel K , Cooper Cyrus , Díez-Pérez Adolfo , Prieto-Alhambra Daniel
Published: March 2014

The objective of this work was to study the associations between ankylosing spondylitis (AS) and clinical vertebral and nonvertebral fractures. Data from a large population-based public health database in Spain, Sistema d'Informació per al Desenvolupament de l'Investigació en Atenció Primària (SIDIAP), were used in this parallel cohort study. All participants registered in SIDIAP on January 1, 2006, were screened to identify those with a diagnosis of AS. Five age-matched, gender-matched, and general practice surgery–matched controls were selected for each patient with AS. All participants were followed until December 31, 2011, transfer out date, or death date. Fractures during this time were classified as vertebral or nonvertebral. Adjustment was made for potential confounders (tobacco smoking, alcohol consumption, body mass index, and use of oral steroids). Of 4,920,353 eligible patients in SIDIAP, 6474 AS patients with matched controls (n = 32,346) were available. A higher proportion of patients with AS versus controls had clinical vertebral (0.86% versus 0.41%) and nonvertebral (3.4% versus 2.7%) fractures. Adjusted Cox regression models showed an increased risk of clinical vertebral (hazard ratio [HR] 1.93; 95% confidence interval [CI], 1.39 to 2.68; p < 0.001) and nonvertebral (HR 1.19; 95% CI, 1.02 to 1.39; p = 0.03) fractures among patients with AS. However, the observed increased risks were apparent only in those not on regular nonsteroidal anti-inflammatory drugs (NSAIDs). There were no interactions with inflammatory bowel disease, psoriasis, or previous back pain. Patients with AS are at increased risk of vertebral and nonvertebral clinical fractures, independently of various risk factors. Regular use of NSAIDs appears to eliminate the excess fracture risk related to AS, but the mechanisms involved are unknown. © 2014 American Society for Bone and Mineral Research
Determination of Herbicide Difenzoquat Methyl Sulfate in Citruses and Baby Juices by Kinetic‐Spectrophotometric Method and HPLC Method
Authors: Pecev‐Marinković Emilija T. , Grahovac Zora M. , Mitić Snežana S. , Pavlović Aleksandra N. , Rašić Mišić Ivana D. , Mitić Milan N.
Published: March 2014

The purpose of this paper is to present a new kinetic‐spectrophotometric method which involve inexpensive equipment and which can be applied by all analyst who have to determine difenzoquate methyl sulfate (DFQ) residues in citruses and baby juices. The method is based on the inhibited effect of DFQ on the oxidation of sulfanile acid (SA) by hydrogen peroxide in phosphate buffer in presence Cu(II) ion. The reaction was monitored spectrophotometrically by measuring the increase in absorbance of the reaction product at 370 nm. The proposed inhibited method permits determination of DFQ over the range 0.36 to 1.80 μg/mL and 1.80 to 7.20 μg/mL, with quantification limit of 0.184 μg/mL. The relative standard deviations are 0.73‐2.90% for the concentration interval of DFQ 1.80‐0.36 μg/mL. The method was successfully applied to determination of DFQ residues in citruses and baby juices. The HPLC method is used to verify the results. The results obtained for the same samples by the two methods are quite comparable.
Controlling pH in biological depuration of industrial wastewater to enable micropollutant removal using a further advanced oxidation process
Authors: Rivas Ibáñez Gracia , Casas López José Luis , Esteban García Belén , Sánchez Pérez José Antonio
Published: March 2014

BACKGROUND

The accumulation of bicarbonates during the biological treatment of high organic strength wastewater has a negative impact on the remaining micropollutant removal through chemical oxidation due to its scavenging effect on hydroxyl radicals. In this study, a lab‐scale sequencing batch reactor (SBR) was operated at circumneutral pH to avoid inorganic carbon accumulation, followed by Fenton and photo‐Fenton processes to treat an agro‐food industrial effluent with acetamiprid as a model pollutant at 100 µg L−1. A cost analysis of the operation strategy was performed.

RESULTS

The pH control did not affect SBR efficiency (98% organic carbon biodegradation) but gave rise to different inorganic carbon concentrations in the effluents: 75.32, 10.81 and 5.7 mg L−1 at pH 8.0, 7.0 and 6.5, respectively. Both Fenton and photo‐Fenton resulted in complete acetamiprid removal at pH 6.5 and 7.0 with high iron dosage (up to 80 mg L−1) but only photo‐Fenton achieved this at acidic pH with 20 mg Fe L−1.

CONCLUSION

To remove micropollutant from biotreated wastewater by Fenton processes it is highly recommended to control pH at circumneutral values during the biotreatment. The reactant cost analysis showed a reduction of ∼80% to remove the micropollutant, even with photo‐Fenton being carried out at pH 2.8. © 2014 Society of Chemical Industry
N‐doped TiO2/s‐PS aerogels for photocatalytic degradation of organic dyes in wastewater under visible light irradiation
Authors: Vaiano Vincenzo , Sacco Olga , Sannino Diana , Ciambelli Paolo , Longo Simona , Venditto Vincenzo , Guerra Gaetano
Published: March 2014

BACKGROUND

Heterogeneous photocatalysis for the degradation of non‐biodegradable organic contaminants in wastewater is an alternative to traditional treatment techniques. Since the applications developed employ photocatalysts in powder form, a main disadvantage remains related to the recovery of photocatalysts from the treated wastewater, resulting in damage and shorter lifetime for the recirculation pumps. Structured photocatalysts offer a valid solution to simplify the process; however, they have to guarantee light transmission, long‐term stability under different operating conditions and under mechanical stress.

RESULTS

The photocatalytic performances of N‐doped TiO2 nanocomposite syndiotactic polystyrene aerogels (Nt‐sPS) were analyzed in the presence of visible light. A widely used model pollutant, methylene blue (MB), was chosen to verify the photocatalytic performance. After about 180 min of irradiation, on Nt‐sPS, the conversion of MB reached 30%, higher than that obtained (16%) when the photocatalyst is suspended as powder in the liquid reaction medium.

CONCLUSION

N‐doped TiO2, obtained by direct nitration during the hydrolysis of titanium tetraisopropoxide with ammonia solutions, was immobilized in s‐PS aerogels, yielding high activity in the removal of methylene blue under visible light irradiation, in comparison with N‐doped TiO2 dispersed as powder in solution. © 2014 Society of Chemical Industry
Clinical trial registries are of minimal use for identifying selective outcome and analysis reporting
Authors: Norris Susan L. , Holmer Haley K. , Fu Rongwei , Ogden Lauren A. , Viswanathan Meera S. , Abou‐Setta Ahmed M.
Published: March 2014

Objective

This study aimed to examine selective outcome reporting (SOR) and selective analysis reporting (SAR) in randomized controlled trials (RCTs) and to explore the usefulness of trial registries for identifying SOR and SAR.

Study Design and Setting

We selected one “index outcome” for each of three comparative effectiveness reviews (CERs) of pharmacotherapy and extracted data on this outcome from trial registries and from study publications.

Results

Among 50 RCTs published since 2005 and reporting the index outcome, only 50% were listed in registries; 90% of RCTs were assessed as having SOR or SAR. The index outcome in the registry was different from that in the publication in 75% of trials in two CERs, and not specified at all in the third. Reported outcomes and analyses were not consistent between the publication's methods section and the results section in 33% and 46% of the two CERs where the index outcome was a benefit. There were no statistically significant predictors of SOR and SAR in our small sample where some predictors lacked variability.

Conclusion

The SOR and SAR were frequent in this pilot study, and the most common type of SOR was the publication of outcomes that were not pre‐specified. Trial registries were of little use in identifying SOR and of no use in identifying SAR. Copyright © 2014 John Wiley & Sons, Ltd.
Evaluation of toxicological impacts on Sprague–Dawley rat by successively low dose of aflatoxin B1
Authors: Wei Wei , Li Rui , He Liang , Wang Xu , Ji Xiaofeng , Zhou Yu
Published: March 2014

BACKGROUND

Aflatoxins (AFs) are a group of potent mycotoxins that frequently pollute agro‐products and animal feeds. For complex reasons, the regulatory limits of AFs differ from nation to nation. In this study, feedstuffs contaminated with various concentrations of aflatoxin B1 (AFB1) corresponding to AF regulatory limits of major agro‐product importing and exporting nations were tested in Sprague–Dawley rats, and the toxicological results were evaluated.

RESULTS

During the trial period, no poisoning behavior was observed and no animals died. No significant differences in body weight were observed between AFB1‐contaminated and control rats. However, various negative impacts on liver and kidney functions were observed in AFB1‐contaminated groups, and these negative impacts were positively correlated with AFB1 concentrations. At concentrations of 4–50 µg kg−1, AFB1 tolerance was observed for the liver after 15 days of testing, but this tolerance was not observed for the kidney.

CONCLUSION

Low concentrations of AFB1 still induced obvious toxicological impacts on Sprague–Dawley rats, and the negative effects were aggravated by increasing the AFB1 dose and feeding time. Therefore strict AF regulatory limits are suggested for food safety administration, especially for the low‐income nations with higher hepatitis B virus prevalence. © 2014 Society of Chemical Industry
Effects of the dietary incorporation of olive leaves on growth performance, digestibility, blood parameters and meat quality of growing pigs
Authors: Paiva‐Martins Fátima , Ribeirinha Teresa , Silva Aníbal , Gonçalves Rita , Pinheiro Victor , Mourão José L , Outor‐Monteiro Divanildo
Published: March 2014

BACKGROUND

In a preliminary study the oxidative stability and tocopherol content of pork meat were shown to be improved by olive leaf (OL) feed supplementation at 50 and 100 g kg−1. However, growth performance was affected negatively. Therefore the objective of the present study was to assess the influence of OL supplementation at a lower level on feed digestibility, growth performance and meat quality.

RESULTS

Pigs were fed a basal diet (control), a basal diet with 25 g OL kg−1 (OL2.5) or a basal diet with 50 g OL kg−1 (OL5). The incorporation of OL significantly decreased growth rates (P = 0.010) and backfat thickness (P = 0.035) and increased feed/gain ratio (P = 0.032) in the OL5 group. Feed/gain ratio increased more for females (P = 0.001). The incorporation of OL decreased the crude fat (P = 0.006) and protein (P = 0.037) digestibility of both OL diets. Nevertheless, OL was effective in increasing the tocopherol content of meat (P = 0.009). However, meat from pigs fed the OL diets showed similar conjugated diene content, pH and colour parameters to that from pigs fed the control diet, even after 6 days of storage at 4 °C.

CONCLUSION

The data indicate that olive leaves may be included in pig diets at 25 g kg−1 in order to improve the tocopherol content of meat without excessively compromising growth performance. © 2014 Society of Chemical Industry