bluuebunny/crossref_metadata_2025 huggingface dataset:
Polyols and polyurethane foams from acid‐catalyzed biomass liquefaction by crude glycerol: Effects of crude glycerol impurities
Authors: Hu Shengjun , Li Yebo
Published: April 2014

The effects of crude glycerol impurities on acid‐catalyzed biomass liquefaction by crude glycerol were investigated. Salts (i.e., NaCl and Na2SO4) decreased biomass conversion ratios and negatively affected the properties of polyols produced. Regression models were developed and validated as appropriate for describing the relationships between organic impurities and biomass conversion ratios and between organic impurities and the hydroxyl number of polyols. Polyols produced from crude glycerol containing 0–45% organic impurities showed the hydroxyl number varying from 1301 to 700 mg KOH/g, acid number from 19 to 28 mg KOH/g, viscosity from 2.4 to 29.2 Pa s, and molecular weight (Mw) from 244 to 550 g/mol. Crude glycerol containing 40–50 wt % of organic impurities was suitable to produce polyols with suitable properties for rigid and/or semi‐rigid polyurethane (PU) foam applications. The produced PU foams showed density and compressive strength comparable to those derived from petrochemical solvent‐based liquefaction processes. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40739.
Friction and wear properties of dumbbell‐shaped jute fiber‐reinforced friction materials
Authors: Ma Yunhai , Liu Yucheng , Ma Shengsheng , Wang Hubiao , Gao Zhihui , Sun Junjie , Tong Jin , Guo Li
Published: April 2014

The surfaces of jute fibers (Corchorus capsularis L.) were processed to have different dumbbell‐shaped spacing (5 mm, 10 mm, 15 mm, and 20 mm), and the physical properties of the modified surfaces of the jute fibers were evaluated in this study. The dumbbell‐shaped jute fiber (DJF)‐reinforced friction materials were prepared through compression mold. The friction and wear performance of the DJF were tested using a friction material tester at constant speed. The results showed that the dumbbell‐shaped spacing has less influence on the friction coefficients of friction materials. The friction coefficients of DJF have bigger fluctuation compared with that of straight fiber during the temperature‐increasing procedure. The wear rate of DJF with dumbbell‐shaped spacing of 15 mm was the lowest, except for that when the temperatures were about 200–250°C. Morphologies of wear surfaces of DJF were observed using scanning electron microscopy and the friction characteristics were analyzed. The results showed that reinforced with DJFs in the friction materials can reduce the specific wear rate and the variation in friction coefficient compared with that of straight jute fibers. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40748.
Facile Synthesis of Ultrathin Lepidocrocite Nanosheets from Layered Precursors
Authors: Yang Yijun , Zhong Yeteng , Wang Xi , Ma Ying , Yao Jiannian
Published: April 2014

Ultrathin two‐dimensional nanosheets have been widely studied because of their peculiar properties and promising applications. As a typical layered material, successful exfoliation of freestanding ultrathin lepidocrocite (γ‐FeOOH) nanosheets from the bulk material has not been reported to date. Herein, we report a facile synthetic route to prepare ultrathin lepidocrocite nanosheets with a thickness of approximately 2–3 nm from FeOx–propanediol layered precursors through weakening of the hydrogen bonds during the crystallization process. The ultrathin morphology and single‐crystal structure of the nanosheets were confirmed by transmission electron microscopy, X‐ray diffraction, and atomic force microscopy. The formation process of these nanosheets demonstrated simultaneous exfoliation and crystallization of lepidocrocite in basic aqueous solution. The obtained ultrathin nanosheets exhibited a much lower Néel temperature (18.3 K) than bulk lepidocrocite and weak ferromagnetic behavior below this temperature.
Fibroblast growth factor signaling and inhibition in non‐small cell lung cancer and their role in squamous cell tumors
Authors: Salgia Ravi
Published: April 2014

With the introduction of targeted agents primarily applicable to non‐small cell lung cancer (NSCLC) of adenocarcinoma histology, there is a heightened unmet need in the squamous cell carcinoma population. Targeting the angiogenic fibroblast growth factor (FGF)/FGF receptor (FGFR) signaling pathway is among the strategies being explored in squamous NSCLC; these efforts are supported by growth‐promoting effects of FGF signaling in preclinical studies (including interactions with other pathways) and observations suggesting that FGF/FGFR‐related aberrations may be more common in squamous versus adenocarcinoma and other histologies. A number of different anti‐FGF/FGFR approaches have shown promise in preclinical studies. Clinical trials of two multitargeted tyrosine kinase inhibitors are restricting enrollment to patients with squamous NSCLC: a phase I/II trial of nintedanib added to first‐line gemcitabine/cisplatin and a phase II trial of ponatinib for previously treated advanced disease, with the latter requiring not only squamous disease but also a confirmed FGFR kinase amplification or mutation. There are several ongoing clinical trials of multitargeted agents in general NSCLC populations, including but not limited to patients with squamous disease. Other FGF/FGFR‐targeted agents are in earlier clinical development. While results are awaited from these clinical investigations in squamous NSCLC and other disease settings, additional research is needed to elucidate the role of FGF/FGFR signaling in the biology of NSCLC of different histologies.
Interesse von Jugendlichen an Naturwissenschaften
Authors: Dierks Pay Ove , Höffler Tim , Parchmann Ilka
Published: April 2014

Interesse ist von großer Bedeutung für die Lernmotivation und die spätere Studien‐ oder Berufswahl. In diesem Beitrag wird der aktuelle Stand der Forschung zum Interesse allgemein und spezifisch an den Naturwissenschaften dargelegt. Ergänzend wird eine Adaption des „RIASEC‐Modells“ nach John L. Holland zur Charakterisierung von Interessen in den Naturwissenschaften vorgestellt. Darauf aufbauend gibt dieser Beitrag einen zusammenfassenden Überblick über Ansätze schulischer und außerschulischer Förderangebote.
Stereoselective Reduction of 1‐O‐Isopropyloxygenipin Enhances Its Neuroprotective Activity in Neuronal Cells from Apoptosis Induced by Sodium Nitroprusside
Authors: Wang Rikang , Yang Jian , Liao Sufen , Xiao Gaokeng , Luo Jun , Zhang Lang , Little Peter J. , Chen Heru , Zheng Wenhua
Published: April 2014

Genipin is a Chinese herbal medicine with both neuroprotective and neuritogenic activity. Because of its unstable nature, efforts have been to develop more stable genipin derivatives with improved biological activities. Among the new compounds reported in the literature, (1R)‐isopropyloxygenipin (IPRG001) is a more stable but less active compound compared with the parent, genipin. Here, two new IPRG001 derivatives generated by stereoselective reduction of the C6=C7 double bond were synthesized. The 1R and 1S isomers of (4aS,7S,7aS)‐methyl‐7‐(hydroxymethyl)‐1‐isopropoxy‐1,4a,5,6,7,7a‐hexahydrocyclopenta[c]pyran‐4‐carboxylate (CHR20 and CHR21) were shown to be very stable both in high‐glucose cell culture medium and in mice serum at 37 °C. Evaluation using an MTT assay and Hoechst staining showed that CHR20 and CHR21 promote the survival of rat adrenal pheochromocytoma (PC12) and retinal neuronal (RGC‐5) cells from injury induced by sodium nitroprusside (SNP). The neuroprotective effects of CHR20 and CHR21 were greater than both isomers of IPRG001, the parent compounds. These results indicate that reduction of 1‐O‐isopropyloxygenipin enhances its neuroprotective activity without affecting its stability.
Synthesis and Biological Evaluation of Imidazo[2,1‐b][1,3,4]thiadiazole‐Linked Oxindoles as Potent Tubulin Polymerization Inhibitors
Authors: Kamal Ahmed , Rao M. P. Narasimha , Das Pompi , Swapna P. , Polepalli Sowjanya , Nimbarte Vijaykumar D. , Mullagiri Kishore , Kovvuri Jeshma , Jain Nishant
Published: April 2014

A series of imidazo[2,1‐b][1,3,4]thiadiazole‐linked oxindoles composed of an A, B, C and D ring system were synthesized and investigated for anti‐proliferative activity in various human cancer cell lines; test compounds were variously substituted at rings C and D. Among them, compounds 7 ((E)‐5‐fluoro‐3‐((6‐p‐tolyl‐2‐(3,4,5‐trimethoxyphenyl)‐imidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl)methylene)indolin‐2‐one), 11 ((E)‐3‐((6‐p‐tolyl‐2‐(3,4,5‐trimethoxyphenyl)imidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl)methylene)indolin‐2‐one), and 15 ((E)‐6‐chloro‐3‐((6‐phenyl‐2‐(3,4,5‐trimethoxyphenyl)imidazo[2,1‐b][1,3,4]thiadiazol‐5‐yl)methylene)indolin‐2‐one) exhibited potent anti‐proliferative activity. Treatment with these three compounds resulted in accumulation of cells in G2/M phase, inhibition of tubulin assembly, and increased cyclin‐B1 protein levels. Compound 7 displayed potent cytotoxicity, with an IC50 range of 1.1–1.6 μM, and inhibited tubulin polymerization with an IC50 value (0.15 μM) lower than that of combretastatin A‐4 (1.16 μM). Docking studies reveal that compounds 7 and 11 bind with αAsn101, βThr179, and βCys241 in the colchicine binding site of tubulin.
The Integrin Ligand c(RGDf(NMe)Nal) Reduces Neointimal Hyperplasia in a Polymer‐Free Drug‐Eluting Stent System
Authors: Rechenmacher Florian , Steigerwald Kristin , Laufer Burkhardt , Neubauer Stefanie , Kapp Tobias G. , Li Liang , Mas‐Moruno Carlos , Joner Michael , Kessler Horst
Published: April 2014

The use of highly active and selective integrin ligands in combination with stent implantation is emerging as a promising alternative to the release of classical immunosuppressive drugs by current drug‐eluting stents (DES), which has been associated with delayed vascular healing and late stent thrombosis. Herein we present the development and biological evaluation of the integrin ligand c(RGDf(NMe)Nal) as a potent anti‐proliferative molecule that targets coronary artery smooth muscle cells (CASMCs). This peptide showed an antagonistic activity for αvβ3 and αvβ5 in the low‐nanomolar range, and selectivity against the platelet receptor αIIbβ3. In vitro, it efficiently inhibited the proliferation of CASMCs, displaying higher potency than the anti‐tumor drug candidate cilengitide. This peptide was then loaded into a polymer‐free bare metal stent (BMS), and its release studied at different time points. Up to seven days of elution, the peptide‐coated stents retained high anti‐proliferative activity toward CASMCs. Finally, the peptide was examined in vivo in a polymer‐free DES system in a rabbit iliac artery model. After 28 days of implantation, histopathological analysis revealed that the peptide clearly decreased neointimal growth and improved vessel healing and re‐endothelialization compared with the FDA‐approved Cypher DES. Our study shows that this type of lipophilic integrin ligand, when eluted from a polymer‐free stent system, has the potential to successfully decrease in‐stent restenosis in the absence of delayed vascular healing.
A negotiation‐based method for task allocation with time constraints in open grid environments
Authors: Kong Yan , Zhang Minjie , Ye Dayong
Published: April 2014

This paper addresses the task allocation problem in an open, dynamic grid environments and service‐oriented environments. In such environments, both grid/service providers and consumers can be modelled as intelligent agents. These agents can leave and enter the environment freely at any time. Task allocation under time constraints becomes a challenging issue in such environments because it is difficult to apply a central controller during the allocation process due to the openness and dynamism of the environments. This paper proposes a negotiation‐based method for task allocation under time constraints in an open, dynamic grid environment, where both consumer and provider agents can freely enter or leave the environment. In this method, there is no central controller available, and agents negotiate with each other for task allocation based only on local views. The experimental results show that the proposed method can outperform the current methods in terms of the success rate of task allocation and the total profit obtained from the allocated tasks by agents under different time constraints. Copyright © 2014 John Wiley & Sons, Ltd.
Diagnosis of the Redox Levels of TCNQF4 Compounds Using Vibrational Spectroscopy
Authors: Haworth Naomi L. , Lu Jinzhen , Vo Nguyen , Le Thanh Hai , Thompson Christopher D. , Bond Alan M. , Martin Lisandra L.
Published: April 2014

The vibrational spectroscopy of TCNQF40, TCNQF41− and TCNQF42− has been investigated by means of density functional theory. Band assignments in infrared and Raman spectra have been clarified and a series of diagnostics developed for redox level characterisation of TCNQF4 compounds. In the CC stretching region (1460–1600 cm−1), TCNQF40 and TCNQF41− show two bands, with the more energetic being at 1600 cm−1 in TCNQF40 and at approximately 1535 cm−1 in TCNQF41−; in TCNQF42− both modes absorb below 1500 cm−1, often merging to give a single band. In the CF and endocyclic CC stretching region (1290 and 1360 cm−1), TCNQF40 and TCNQF41− show strong bands, whereas TCNQF42− absorbs weakly or not at all. (Additional bands, e.g. from co‐crystallised solvent molecules, may complicate this region.) In the nitrile stretching region (2000–2250 cm−1), modes are highly sensitive to nitrile coordination by metal cations. All three redox levels can produce bands above 2200 cm−1, however bands below 2150 cm−1 are usually due to TCNQF42−. This sensitivity to coordination is likely to affect the spectra of many organic molecular ions.
Silver Coordination Polymers Based on p‐Cyanophenylsilanes as Ligands
Authors: Blankschein Bianca , Schulz Axel , Villinger Alexander , Wustrack Ronald
Published: April 2014

Differently substituted p‐cyanophenylsilanes, Me4−nSi(C6H4CN)n, (n=2, 3, 4), PhSi(C6H4CN)3, cycHexSi(C6H4CN)3 (cycHex=cyclohexyl), and MePhSi(C6H4CN)2, were prepared and fully characterized. Their coordination behavior was studied by utilizing silver salts of the type AgX (X=O3SCF3−, CO2CF3−), which led to coordination polymers. One‐dimensional chains were observed for the bidentate p‐cyanophenylsilane ligands, whereas two‐ and three‐dimensional networks, including macrometalacycles, were found for the tridentate ligand. Treatment of AgO2CCF3 with the tetradentate ligand Si(C6H4CN)4 led to the formation of a diamond‐like three‐dimensional network with two interpenetrating nets linked by bridging Ag2(CF3CO2)2 dimers. X‐ray structures show a wide range of close Ag⋅⋅⋅Ag distances in the polymers, which are dependent on the ligand and the anion utilized.
Fe3O4/Carbon Hybrid Nanoparticle Electrodes for High‐Capacity Electrochemical Capacitors
Authors: Lee Jun Seop , Shin Dong Hoon , Jun Jaemoon , Lee Choonghyeon , Jang Jyongsik
Published: April 2014

Fe3O4/carbon hybrid nanoparticles (FeCHNPs) were fabricated using dual‐nozzle electrospraying, vapor deposition polymerization (VDP), and carbonization. FeOOH nanoneedles decorated with polypyrrole (PPy) nanoparticles (FePNPs) were fabricated by electrospraying pristine PPy mixed with FeCl3 solution, followed by heating stirring reaction. A PPy coating was then formed on the FeOOH nanoneedles through a VDP process. FeCHNPs were produced through carbonization of PPy and FeOOH phase transitions. These hybrid carbon nanoparticles (NPs) were used to build electrodes of electrochemical capacitors. The specific capacitance of the FeCHNPs was 455 F g−1, which is larger than that of pristine PPy NPs (105 F g−1) or other hybrid PPy NPs. Furthermore, the FeCHNP‐based capacitors exhibited better cycle stability during charge–discharge cycling than other hybrid NP capacitors. This is because the carbon layer on the Fe3O4 surface formed a protective coating, preventing damage to the electrode materials during the charge–discharge processes. This fabrication technique is an effective approach for forming stable carbon/metal oxide nanostructures for energy storage applications.
Rapid Trifluoromethylation and Perfluoroalkylation of Five‐Membered Heterocycles by Photoredox Catalysis in Continuous Flow
Authors: Straathof Natan J. W. , Gemoets Hannes P. L. , Wang Xiao , Schouten Jaap C. , Hessel Volker , Noël Timothy
Published: April 2014

Trifluoromethylated and perfluoroalkylated heterocycles are important building blocks for the synthesis of numerous pharmaceutical products, agrochemicals and are widely applied in material sciences. To date, trifluoromethylated and perfluoroalkylated hetero‐aromatic systems can be prepared utilizing visible light photoredox catalysis methodologies in batch. While several limitations are associated with these batch protocols, the application of microflow technology could greatly enhance and intensify these reactions. A simple and straightforward photocatalytic trifluoromethylation and perfluoroalkylation method has been developed in continuous microflow, using commercially available photocatalysts and microflow components. A selection of five‐membered hetero‐aromatics were successfully trifluoromethylated (12 examples) and perfluoroalkylated (5 examples) within several minutes (8–20 min).
Thermochromic and Piezochromic Effects of CoII–Imidazole‐Based Supramolecular Gels as Logic Gates
Authors: Jung Sung Ho , Moon Jong Hun , Lee Jin Yong , Jung Jong Hwa
Published: April 2014

We demonstrate that the imidazole‐based ligand 1 efficiently produces a coordination polymer gel by simple mixing with Co2+ ion. When the molar ratio of CoCl2 to ligand 1 was less < 1, a red sol was obtained, indicating the formation of an octahedral (Oh) complex species as occurs with Co(NO3)2. In contrast to G1, when the amount of CoCl2 employed was more than 1 equiv., the color of the gel changed from red to blue (G2), indicating the formation of mainly a tetrahedral (Td) complex species. The ionochromic and the piezochromic effects of imidazole‐based suprmolecular gel with Co2+ were investigated. These effects of supramolecular gel were controlled by various anions of cobalt, which are due to coordination geometric change of gels. Interestingly, the ionochromic and piezochromic effects of G1 act as AND and OR logic gates in the solid and the gel state.
Sulfur–Carbon Bond Formation through Ring‐Opening of Triazolothiadiazole with Organometallics
Authors: Othman Raja Ben , Massip Stéphane , Marchivie Mathieu , Jarry Christian , Vercouillie Johnny , Chalon Sylvie , Guillaumet Gérald , Suzenet Franck , Routier Sylvain
Published: April 2014

An efficient and convenient method was developed for the formation of S‐substituted thiotriazoles through an unprecedented organometallic addition and subsequent ring‐opening sequence of 3‐substituted [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazole. The method is applicable to a wide range of substrates containing different functional groups and furnishes excellent yields of the corresponding N‐unsubstituted 3‐ or 5‐alkyl, aryl, alkynyl and alkenyl sulfanyl‐1,2,4‐triazole products.
Toward Feedback Controlled Anesthesia: Automated Flow Analytical System for Electrochemical Monitoring of Propofol in Serum Solutions
Authors: Rainey Felynncia , Kivlehan Francine , Chaum Edward , Lindner Ernő
Published: April 2014

For monitoring of the popular anesthetic drug propofol an automatic flow analytical system (AFAS) has been built that allows the quantitative measurement of electrochemically active compounds in continuous flow, stopped flow and flow injection analysis (FIA) modes. The performance characteristics of the AFAS is demonstrated using a microfabricated planar electrochemical cells in combination with a ∼15 µL volume flow cell. To perform continuous monitoring experiments and the analysis of individual propofol samples an organic membrane‐coated voltammetric sensor has been implemented into the AFAS. The membrane coating prevents electrode fouling, provides outstanding detection limit and selectivity for the voltammetric working electrode.
The unfolded protein response affects readthrough of premature termination codons
Authors: Oren Yifat S , McClure Michelle L , Rowe Steven M , Sorscher Eric J , Bester Assaf C , Manor Miriam , Kerem Eitan , Rivlin Joseph , Zahdeh Fouad , Mann Matthias , Geiger Tamar , Kerem Batsheva
Published: April 2014

One‐third of monogenic inherited diseases result from premature termination codons (PTCs). Readthrough of in‐frame PTCs enables synthesis of full‐length functional proteins. However, extended variability in the response to readthrough treatment is found among patients, which correlates with the level of nonsense transcripts. Here, we aimed to reveal cellular pathways affecting this inter‐patient variability. We show that activation of the unfolded protein response (UPR) governs the response to readthrough treatment by regulating the levels of transcripts carrying PTCs. Quantitative proteomic analyses showed substantial differences in UPR activation between patients carrying PTCs, correlating with their response. We further found a significant inverse correlation between the UPR and nonsense‐mediated mRNA decay (NMD), suggesting a feedback loop between these homeostatic pathways. We uncovered and characterized the mechanism underlying this NMD‐UPR feedback loop, which augments both UPR activation and NMD attenuation. Importantly, this feedback loop enhances the response to readthrough treatment, highlighting its clinical importance. Altogether, our study demonstrates the importance of the UPR and its regulatory network for genetic diseases caused by PTCs and for cell homeostasis under normal conditions.
Diffusion MRI: what water tells us about the brain
Authors: Le Bihan Denis
Published: April 2014

Diffusion MRI has been used worldwide to produce images of brain tissue structure and connectivity, in the normal and diseased brain. Diffusion MRI has revolutionized the management of acute brain ischemia (stroke), saving life of many patients and sparing them significant disabilities. In addition to stroke, diffusion MRI is now widely used for the detection of cancers and metastases (breast, prostate, liver). Another major field of application of diffusion MRI regards the wiring of the brain. Diffusion MRI is now used to map the circuitry of the human brain with incredible accuracy, opening up new lines of inquiry for human neuroscience and for the understanding of brain illnesses or mental disorders. Here, as a pioneer of the field, I provide a personal account on the historical development of these concepts over the last 30 years.
A residual‐based Allen–Cahn phase field model for the mixture of incompressible fluid flows
Authors: Vasconcelos D. F. M. , Rossa A. L. , Coutinho A. L. G. A.
Published: April 2014

The hydrodynamics of fluid mixtures is receiving more and more attention in many science and engineering applications. Within the techniques for dealing with front displacements and moving boundaries between different density and/or viscosity fluids, phase fields are a class of models in which a diffusive transition region is taken into account instead of a steep interface. Although these models have a physical motivation, they require the definition of extra parameters. In order to make it less parameter dependent, the classic Allen–Cahn phase field model is modified, exploring its similarities with residual‐based discontinuity‐capturing schemes, making the phase field equation dependent on its own residual. We solve the coupling between incompressible viscous fluid flow and the phase field advective–diffusive–reactive transport to simulate the main processes in interface tension and/or buoyancy driven problems. For the solution of the Navier–Stokes and transport equations, we use a stabilized finite element formulation. The implementation has been performed using the libMesh finite element library, written in C++ , which provides support for adaptive mesh refinement and coarsening. A chemical convection benchmark problem is used to validate the proposed model, and then we solve two bubble interaction problems. Copyright © 2014 John Wiley & Sons, Ltd.
Going Formal or Informal, Who Cares? The Influence of Public Long‐Term Care Insurance
Authors: Bakx Pieter , de Meijer Claudine , Schut Frederik , van Doorslaer Eddy
Published: April 2014

International differences in long‐term care (LTC) use are well documented, but not well understood. Using comparable data from two countries with universal public LTC insurance, the Netherlands and Germany, we examine how institutional differences relate to differences in the choice for informal and formal LTC. Although the overall LTC utilization rate is similar in both countries, use of formal care is more prevalent in the Netherlands and informal care use in Germany. Decomposition of the between‐country differences in formal and informal LTC use reveals that these differences are not chiefly the result of differences in population characteristics but mainly derive from differences in the effects of these characteristics that are associated with between‐country institutional differences. These findings demonstrate that system features such as eligibility rules and coverage generosity and, indirectly, social preferences can influence the choice between formal and informal care. Less comprehensive coverage also has equity implications: for the poor, access to formal LTC is more difficult in Germany than in the Netherlands. Copyright © 2014 John Wiley & Sons, Ltd.
Binding of hepatitis B virus to its cellular receptor alters the expression profile of genes of bile acid metabolism
Authors: Oehler Nicola , Volz Tassilo , Bhadra Oliver D. , Kah Janine , Allweiss Lena , Giersch Katja , Bierwolf Jeanette , Riecken Kristoffer , Pollok Jörg M. , Lohse Ansgar W. , Fehse Boris , Petersen Joerg , Urban Stephan , Lütgehetmann Marc , Heeren Joerg , Dandri Maura
Published: April 2014

Chronic hepatitis B virus (HBV) infection has been associated with alterations in lipid metabolism. Moreover, the Na+-taurocholate cotransporting polypeptide (NTCP), responsible for bile acid (BA) uptake into hepatocytes, was identified as the functional cellular receptor mediating HBV entry. The aim of the study was to determine whether HBV alters the liver metabolic profile by employing HBV-infected and uninfected human liver chimeric mice. Humanized urokinase plasminogen activator/severe combined immunodeficiency mice were used to establish chronic HBV infection. Gene expression profiles were determined by real-time polymerase chain reaction using primers specifically recognizing transcripts of either human or murine origin. Liver biopsy samples obtained from HBV-chronic individuals were used to validate changes determined in mice. Besides modest changes in lipid metabolism, HBV-infected mice displayed a significant enhancement of human cholesterol 7α-hydroxylase (human [h]

CYP7A1

; median 12-fold induction;

P

< 0.0001), the rate-limiting enzyme promoting the conversion of cholesterol to BAs, and of genes involved in transcriptional regulation, biosynthesis, and uptake of cholesterol (human sterol-regulatory element-binding protein 2, human 3-hydroxy-3-methylglutaryl-coenzyme A reductase, and human low-density lipoprotein receptor), compared to uninfected controls. Significant h

CYP7A1

induction and reduction of human small heterodimer partner, the corepressor of hCYP7A1 transcription, was also confirmed in liver biopsies from HBV-infected patients. Notably, administration of Myrcludex-B, an entry inhibitor derived from the pre-S1 domain of the HBV envelope, provoked a comparable murine

CYP7A1

induction in uninfected mice, thus designating the pre-S1 domain as the viral component triggering such metabolic alterations.

Conclusion

: Binding of HBV to NTCP limits its function, thus promoting compensatory BA synthesis and cholesterol provision. The intimate link determined between HBV and liver metabolism underlines the importance to exploit further metabolic pathways, as well as possible NTCP-related viral-drug interactions. (Hepatology 2014;60:1483–1493)
Caveolin-1 is essential for protecting against binge drinking-induced liver damage through inhibiting reactive nitrogen species
Authors: Gao Lei , Zhou Yingchun , Zhong Weichao , Zhao Xiaohua , Chen Chun , Chen Xingmiao , Gu Yong , Chen Jianping , Lv Zhiping , Shen Jiangang
Published: April 2014

Caveolin-1 (Cav-1) is known to participate in many diseases, but its roles in alcoholic liver injury remain unknown. In the present study, we aimed to explore the roles of Cav-1 in protecting hepatocytes from ethanol-mediated nitrosative injury. We hypothesized that Cav-1 could attenuate ethanol-mediated nitrosative stress and liver damage through regulating epidermal growth factor receptor/signal transducer and activator of transcription 3/inducible nitric oxide synthase (EGFR/STAT3/iNOS)-signaling cascades. Ethanol-fed mice had time- and dose-dependent increases of Cav-1 in serum and liver with peak increase at 12 hours. Compared to wild-type mice, Cav-1 deficiency mice revealed higher expression of iNOS, higher levels of nitrate/nitrite and peroxynitrite, and had more serious liver damage, accompanied with higher levels of cleaved caspase-3 and apoptotic cell death in liver, and higher levels of alanine aminotransferase and aspartate aminotransferase in serum. Furthermore, the results revealed that the ethanol-mediated Cav-1 increase was in an extracellular signal-regulated kinase–dependent manner, and Cav-1 protected hepatocytes from ethanol-mediated apoptosis by inhibiting iNOS activity and regulating EGFR- and STAT3-signaling cascades. In agreement with these findings, clinical trials in human subjects revealed that serum Cav-1 level was time dependently elevated and peak concentration was observed 12 hours after binge drinking. Alcohol-induced liver lesions were negatively correlated with Cav-1 level, but positively correlated with nitrate/nitrite level, in serum of binge drinkers. Conclusions: Cav-1 could be a cellular defense protein against alcoholic hepatic injury through inhibiting reactive nitrogen species and regulating EGFR/STAT3/iNOS-signaling cascades. (Hepatology 2014;60:687–699)
Donor‐Acceptor Hybrids for Organic Electronics
Authors: Espíldora Eva , Delgado Juan Luis , Martín Nazario
Published: April 2014

This review deals with functional molecules able to transfer one electron from the donor to the acceptor moiety upon light irradiation. Donor‐bridge‐acceptor molecular systems are of interest for a wide variety of applications, namely artificial photosynthetic architectures and materials for organic photovoltaic devices. In the respective sections, we have addressed some of the most recent and remarkable examples to explain the construction of artificial photosynthetic systems by means of a variety of remarkable photo‐ and electro‐active electron donor molecules covalently or supramolecularly connected to a fullerene unit as the electron acceptor unit. We have also systematically reviewed the most efficient fullerene derivatives used for photovoltaic applications by blending with different semiconducting organic polymers or small molecules, affording all‐organic solar cells.
Heparin surfaces: Impact of immobilization chemistry on hemocompatibility and protein adsorption
Authors: Gore Savannah , Andersson Jonas , Biran Roy , Underwood Clayton , Riesenfeld Johan
Published: April 2014

Immobilization of heparin to surfaces has been used for decades to reduce the thrombogenicity of blood contacting devices. This study evaluates how the mode of covalent heparin bonding affects the hemocompatibility and uptake of antithrombin on surfaces in whole blood. End‐point attached (EPA) heparin, using the proprietary Carmeda® Bioactive Surface (CBAS® Surface), was compared with other methods of covalent heparin bonding that typically yield multiple covalent linkages (using reductive amination of periodate oxidized native heparin or EDC coupling of native heparin). All heparin surfaces were immobilized on flexible polyvinyl chloride tubing and exposed to fresh non‐anticoagulated blood in an in vitro recirculating Chandler loop blood model. After exposure, biomarkers for coagulation and platelet activation were analyzed in the solution phase, and adsorbed plasma proteins were eluted from the heparin surfaces and measured for surface concentration of antithrombin and total adsorbed protein. Only the EPA‐heparin surface conferred thromboresistance, as observed by the absence of clotting. Attachment and activation of platelets as well as activation of the clotting cascade was significantly lower on the EPA‐heparin surface when compared with the other heparin surfaces. In addition, antithrombin constituted ∼40% of the total adsorbed plasma protein concentration on the EPA‐heparin surfaces. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1817–1824, 2014.
Spontaneous scaling down of femtosecond laser‐induced apertures towards the 10‐nanometer level: the excitation of quasistatic surface plasmons
Authors: Huang Min , Xu Zhizhan
Published: April 2014

During ultrafast laser ablation on ZnO, the feature sizes of laser‐induced apertures always decrease spontaneously with the pulse increasing and the crater extending, and may eventually approach an astonishing 10‐nm scale, an ultradeep‐subwavelength laser–solid interaction regime relating new physics in laser‐induced damage. Based on the fundamental theories of plasmonics, it is proposed that the spontaneous scaling‐down originates in the conversion of physical regimes of plasmonic interaction from the optical regime to the electrostatic regime, which arouses quasistatic SPs with interaction scales far beyond the diffraction limit and results in ultrafast, nonthermal ablation for extraordinary electrostatic field enhancement. Basically, “nanoscale” eliminates electromagnetic retardation effects greatly, brings an instantaneous respond to the incident field, and arouses electrostatic interactions with giant local‐field enhancement, which may exert tremendous electrostatic forces on superficial electrons and ions and eventually lead to an “ultrafast” electrostatic nanoexplosion. Thus, the characteristics of simultaneous “nanoscale” and “ultrafast” arise spontaneously in femtosecond laser ablation.
Role of Organoclay in Controlling the Morphology and Crystal‐Growth Behavior of Biodegradable Polymer‐Blend Thin Films Studied Using Atomic Force Microscopy
Authors: Malwela Thomas , Ray Suprakas Sinha
Published: April 2014

This study reports the effect of organically modified nanoclay on the morphology and crystal‐growth behavior of biodegradable polylactide/poly[(butylene succinate)‐co‐adipate] (PLA/PBSA) blend thin films with the average thickness of 280 nm. The neat and organically modified blended thin films were cast on silicon (001) substrate using a spin coater. Blended composite thin films with three different types of organically modified clays were prepared, and the impact of the nature of the pristine clays, their organic modifications and their initial d001‐spacing on the morphology and crystal‐growth behavior of the PLA/PBSA blend were studied. An atomic force microscopy equipped with a hot‐stage scanner was used to examine the crystalline morphology of the thin films. The morphology and crystal‐growth behavior of the films were investigated during in situ annealing and cooling from melt. The results indicated that the initial d001‐spacing of the organoclay plays a pivotal role in controlling the morphology of the dispersed phase and hence the crystal‐growth behavior.
Soft Polydimethylsiloxane Thin Elastomeric Films by In Situ Polymerization to be Used as Dielectricum in Actuators
Authors: Circu Monica V. , Ko Yee Song , Gerecke Andreas C. , Opris Dorina M.
Published: April 2014

A low‐viscosity, solvent‐free process for the fabrication of thin silicone films for dielectric elastomer actuators is presented. Octamethylcyclotetrasiloxane and specially designed co‐monomers that function as cross‐linkers are pre‐polymerized to a liquid of low viscosity. This liquid is used to prepare thin films, which are then fully polymerized to a highly transparent, cross‐linked elastomer. The mechanical and electromechanical properties of the films are easily tuned by altering the amount of cross‐linker co‐monomer used.
Viscoelastic Properties of Magnetorheological Elastomers for Damping Applications
Authors: Molchanov Vyacheslav S. , Stepanov Gennady V. , Vasiliev Viktor G. , Kramarenko Elena Yu. , Khokhlov Alexei R. , Xu Zhao‐Dong , Guo Ying‐Qing
Published: April 2014

Magnetorheological elastomers (MRE) have been synthesized on the basis of a silicon compound and a mixture of carbonyl iron particles of sizes 3–5 and 40–80 μm. Their viscoelastic properties have been studied by dynamic shear oscillations of various amplitudes on a stress controlled rheometer. The magnetic response of the obtained materials has been examined in a magnetic field applied perpendicular to the shear plane. It has been shown that under applied magnetic field both the storage G′ and loss G″ moduli became strain‐dependent. The values of G′ and G″ decrease with strain, while their ratio (the loss factor), G″/G′, growths with strain. The higher magnetic field is the more pronounced the strain dependence is. At small strain (up to 1%) MRE demonstrate a giant (more than 10 times) increase of the moduli. Some features of hysteretic behavior of MRE under simultaneously applied magnetic field and external mechanical force have been elucidated. Temperature has a negligible effect on viscoelastic properties and stability of the developed MRE. A damper on the basis of MRE has been designed and its properties have been examined.
Responsive Linear‐Dendritic Block Copolymers
Authors: Blasco Eva , Piñol Milagros , Oriol Luis
Published: April 2014

The combination of dendritic and linear polymeric structures in the same macromolecule opens up new possibilities for the design of block copolymers and for applications of functional polymers that have self‐assembly properties. There are three main strategies for the synthesis of linear‐dendritic block copolymers (LDBCs) and, in particular, the emergence of click chemistry has made the coupling of preformed blocks one of the most efficient ways of obtaining libraries of LDBCs. In these materials, the periphery of the dendron can be precisely functionalised to obtain functional LDBCs with self‐assembly properties of interest in different technological areas. The incorporation of stimuli‐responsive moieties gives rise to smart materials that are generally processed as self‐assemblies of amphiphilic LDBCs with a morphology that can be controlled by an external stimulus. Particular emphasis is placed on light‐responsive LDBCs. Furthermore, a brief review of the biomedical or materials science applications of LDBCs is presented.

image
Fine‐Tuning of Charge‐Conversion Polymer Structure for Efficient Endosomal Escape of siRNA‐Loaded Calcium Phosphate Hybrid Micelles
Authors: Maeda Yoshinori , Pittella Frederico , Nomoto Takahiro , Takemoto Hiroyasu , Nishiyama Nobuhiro , Miyata Kanjiro , Kataoka Kazunori
Published: April 2014

For efficient delivery of siRNA into the cytoplasm, a smart block copolymer of poly(ethylene glycol) and charge‐conversion polymer (PEG‐CCP) is developed by introducing 2‐propionic‐3‐methylmaleic (PMM) amide as an anionic protective group into side chains of an endosome‐disrupting cationic polyaspartamide derivative. The PMM amide moiety is highly susceptible to acid hydrolysis, generating the parent cationic polyaspartamide derivative at endosomal acidic pH 5.5 more rapidly than a previously synthesized cis‐aconitic (ACO) amide control. The PMM‐based polymer is successfully integrated into a calcium phosphate (CaP) nanoparticle with siRNA, constructing PEGylated hybrid micelles (PMM micelles) having a sub‐100 nm size at extracellular neutral pH 7.4. Ultimately, PMM micelles achieve the significantly higher gene silencing efficiency in cultured cancer cells, compared to ACO control micelles, probably due to the efficient endosomal escape of the PMM micelles. Thus, it is demonstrated that fine‐tuning of acid‐labile structures in CCP improves the delivery performance of siRNA‐loaded nanocarriers.

image
Recommended implementation of arterial spin‐labeled perfusion MRI for clinical applications: A consensus of the ISMRM perfusion study group and the European consortium for ASL in dementia
Authors: Alsop David C. , Detre John A. , Golay Xavier , Günther Matthias , Hendrikse Jeroen , Hernandez‐Garcia Luis , Lu Hanzhang , MacIntosh Bradley J. , Parkes Laura M. , Smits Marion , van Osch Matthias J. P. , Wang Danny J. J. , Wong Eric C. , Zaharchuk Greg
Published: April 2014

This review provides a summary statement of recommended implementations of arterial spin labeling (ASL) for clinical applications. It is a consensus of the ISMRM Perfusion Study Group and the European ASL in Dementia consortium, both of whom met to reach this consensus in October 2012 in Amsterdam. Although ASL continues to undergo rapid technical development, we believe that current ASL methods are robust and ready to provide useful clinical information, and that a consensus statement on recommended implementations will help the clinical community to adopt a standardized approach. In this review, we describe the major considerations and trade‐offs in implementing an ASL protocol and provide specific recommendations for a standard approach. Our conclusion is that as an optimal default implementation, we recommend pseudo‐continuous labeling, background suppression, a segmented three‐dimensional readout without vascular crushing gradients, and calculation and presentation of both label/control difference images and cerebral blood flow in absolute units using a simplified model. Magn Reson Med 73:102–116, 2015. © 2014 Wiley Periodicals, Inc.
From social management to social governance: social conflict mediation in China
Authors: Liu Jinfa
Published: April 2014

China currently faces increasingly serious social conflicts. In the past, China's approach to resolving social conflicts was ‘social management’. Now, however, it is turning to the development of ‘social governance’. This change reflects the inability of government acting alone to recognise and to address comprehensively the type of social problems that require co‐ordination of social forces. Our research identifies three dimensions of governance and provides a comparative framework allowing us to illuminate how social governance as conceived in China differs from that in Western countries. Under China's current conditions, the strengthening and development of social governance is a holistic process. Neither market‐centrism nor state‐centrism is pursued, and pure social‐centrism is not the favoured direction of development; the path chosen is rather a state‐led social pluralism. The implications we see for the Government are that it should first transform its own functions to achieve a substantially higher quality of public service. This would put it in a position to empower (civil) society to mobilise multiple and varied social forces to participate so that social conflict can be optimally addressed. Copyright © 2014 John Wiley & Sons, Ltd.
A smart methodology to fabricate electrospun chitosan nanofiber matrices for regenerative engineering applications
Authors: Nada Ahmed A. , James Roshan , Shelke Namdev B. , Harmon Matthew D. , Awad Hassan M. , Nagarale Rajaram K. , Kumbar Sangamesh G.
Published: April 2014

The electrospinning of chitosan remains challenging due to its rigid crystalline structure, insufficient viscosity, and limited solubility in common organic solvents. This work presents a “smart” chitosan modification that allows electrospinning irrespective of molecular weight or deacetylation value and without blending with synthetic polymers. A novel derivative, namely 2‐nitrobenzyl‐chitosan (NB), at various molar compositions of chitosan:2‐nitrobenzaldehyde (1:1 (NB‐1), 1:0.5 (NB‐2), 1:0.25 (NB‐3)) was synthesized by the reaction between amino groups of chitosan and aldehyde groups of 2‐nitrobenzaldehyde. In this Schiff base, 2‐nitrobenzaldehyde protects the amine functionalities of chitosan and improves its solubility in trifluoroacetic acid. 2‐nitrobenzaldehyde is a photoactivatable‐caged compound that cleaves off from iminochitosan on ultraviolet exposure yielding neat chitosan. Derivatives showed improved solubility in trifluoroacetic acid and dynamic viscosities in the range of 1.34 ± 0.7 to 12 ± 0.5 Pa·s based on the degree of substitution and concentration. Electrospinning conditions were optimized to produce bead free nanofibers in the range of 100–600 nm, and concentrations beyond 12% (wt/v) for NB‐1 and NB‐2, and 15% (wt/v) for NB‐3 were suitable. Photolysis did not alter fiber morphology; however, regenerated chitosan matrices were soluble in culture media presumably due to the presence of 2‐nitrosobenzoic acid in trace amounts. Human skin fibroblasts exhibited excellent (>90%) cytocompatibility on treatment with polymer extractions from cross‐linked regenerated chitosan matrices prepared to the ISO standard. Newly synthesized iminochitosan derivatives were very effective against microorganisms including bacteria (Gram‐positive and Gram‐negative), fungi, and yeast. These fiber matrices may serve as scaffolds for a variety of tissue healing and factor delivery applications. Copyright © 2014 John Wiley & Sons, Ltd.
Ultrasound‐mediated transgene expression in endogenous stem cells recruited to bone injury sites
Authors: Shapiro Galina , Kallai Ilan , Sheyn Dmitriy , Tawackoli Wafa , Koh Young Do , Bae Hyun , Trietel Tamar , Goldbart Riki , Kost Joseph , Gazit Zulma , Gazit Dan , Pelled Gadi
Published: April 2014

When fractured, bone can spontaneously heal to a certain extent. In critical‐size defects, in which bone loss is severe, a bone graft is required. Faced with the shortcomings of grafts currently in use—autografts, allografts, and mineral‐based bone substitutes—efforts are being made to establish new methods of bone regeneration. One promising approach involves the use of exogenous gene‐modified mesenchymal stem cells (MSCs), which can rapidly repair large bone defects in animal models. Unfortunately, ex vivo culture of MSCs may add certain complexity to the advancement of this cell therapy to the clinic. Previously, we demonstrated efficient bone regeneration following direct gene delivery to endogenous MSCs that had been attracted to a fracture site. In that study, electroporation was used, but it is an invasive method of gene transfection that may result in tissue damage. Unlike electroporation, sonoporation—the use of ultrasound for gene delivery—is noninvasive, considered safer, and relevant to the clinical setting. In this study, we evaluated the feasibility of ultrasound‐based gene delivery to resident MSCs that had been recruited to a fracture site in different animal models. Our results show transient (up to 21 days) expression of a reporter gene in radial, vertebral, and tibial bone defects in mice, rats, and a minipig. These results could prove beneficial for the next phase of experiments, in which osteogenic genes such as the bone morphogentic proteins (BMPs) could be utilized to achieve bone regeneration in similar challenging conditions of bone tissue loss. Copyright © 2014 John Wiley & Sons, Ltd.
Major influence of the alkyl chain length of poly(2,4‐dialkyl‐3,4‐propylenedioxythiophene) on the surface fibrous structures and hydrophobicity
Authors: Mortier Claudio , Darmanin Thierry , Guittard Frederic
Published: April 2014

We report the synthesis of 2,4‐dialkyl‐3,4‐propylenedioxythiophene monomers with various alkyl chain length (n = 1, 2, 3, 4, 5) and their use for the surface modification by electropolymerization. Surprisingly, there is a drastic decrease in surface hydrophobicity as the alkyl chain length between n = 2 and 3 increases. The decrease is due to a change in the surface morphology from nanofibers to relatively smooth. Indeed, the increase in the alkyl chain length in the 2‐ and 4‐positions induces very high steric hindrances during the polymerization. As a consequence, the oligomers formed in the first instances are smaller and as a consequence more soluble in solution, leading to smoother films. This work opens new strategies for the elaboration of highly hydrophobic poly(3,4‐propylenedioxythiophene) nanofibers for potential biological applications. Copyright © 2014 John Wiley & Sons, Ltd.