bluuebunny/crossref_metadata_2025_split huggingface dataset:
α,β‐Unsaturated Acyl Cyanides as New Bis‐Electrophiles for Enantioselective Organocatalyzed Formal [3+3]Spiroannulation
Authors: Goudedranche Sébastien , Bugaut Xavier , Constantieux Thierry , Bonne Damien , Rodriguez Jean 
Published: December 2013

Abstractα,β‐Unsaturated acyl cyanides are key bis‐electrophile substrates for successful domino enantioselective organocatalyzed Michael‐intramolecular acylation domino sequences. This new reactivity has been applied to the synthesis of enantioenriched azaspiro[4,5]decanone ring systems by a formal [3+3]spiroannulation, constituting a rare example of synthesis of glutarimides in an optically active form.
Physiological Stratification in Electricity‐Producing Biofilms of Geobacter sulfurreducens
Authors: Schrott Germán David , Ordoñez María Victoria , Robuschi Luciana , Busalmen Juan Pablo 
Published: December 2013

AbstractThe elucidation of mechanisms and limitations in electrode respiration by electroactive biofilms is significant for the development of rapidly emerging clean energy production and wastewater treatment technologies. In Geobacter sulfurreducens biofilms, the controlling steps in current production are thought to be the metabolic activity of cells, but still remain to be determined. By quantifying the DNA, RNA, and protein content during the long‐term growth of biofilms on polarized graphite electrodes, we show in this work that current production becomes independent of DNA accumulation immediately after a maximal current is achieved. Indeed, the mean respiratory rate of biofilms rapidly decreases after this point, which indicates the progressive accumulation of cells that do not contribute to current production or contribute to a negligible extent. These results support the occurrence of physiological stratification within biofilms as a consequence of respiratory limitations imposed by limited biofilm conductivity.
Electron‐Ion Relaxation, Phase Transitions, and Surface Nano‐Structuring Produced by Ultrashort Laser Pulses in Metals
Authors: Inogamov N. A. , Zhakhovsky V. V. , Petrov Yu. V. , Khokhlov V.A. , Ashitkov S. I. , Khishchenko K. V. , Migdal K. P. , Ilnitsky D. K. , Emirov Yu. N. , Komarov P. S. , Shepelev V. V. , Miller C.W. , Oleynik I.I. , Agranat M.B. , Andriyash A.V. , Anisimov S.I. , Fortov V.E. 
Published: December 2013

AbstractFundamental physical phenomena in metals irradiated by ultrashort laser pulses with absorbed fluences higher than few tens of mJ/cm2 are investigated. For those fluences, laser‐produced electron distribution function relaxes to equilibrium Fermi distribution with electron temperature Te within a short time of 10‐100 fs. Because the electron subsystem has Te highly exceeding much the ion subsystem temperature Ti the well‐known twotemperature hydrodynamic model (2T‐HD) is used to evaluate heat propagation associated with hot conductive electron diffusion and electron‐ion energy exchange. The model coefficients of electron heat conductivity κ (ϱ, Te, Ti) and electron‐ion coupling parameter α (ϱ, Te) together with 2T equation of state E (ϱ, Te, Ti) and P (ϱ, Te, Ti) are calculated.Modeling with 2T‐HD code shows transition of electron heat wave from supersonic to subsonic regime of prop‐agation. At the moment of transition the heat wave emits a compression wave moving into the bulk of met al. Nonlinear evolution of the compression wave after its separation from the subsonic heat wave till spallation of rear‐side layer of a film is traced in both 2T‐HD modeling and molecular dynamics (MD) simulation.For fluences above some threshold the nucleation of voids in frontal surface layer is initiated by strong tensile wave following the compression wave. If the absorbed fluence is ∼30 % above the ablation threshold than void nucleation develops quickly to heavily foam the molten met al. Long‐term evolution of the metal foam including foam breaking and freezing is simulated. It is shown that surface nano‐structures observed in experiments are produced by very fast cooling of surface molten layer followed by recrystallization of supercooled liquid in disintegrating foam having complex geometry. Characteristic lengths of such surface nanostructures, including frozen pikes and bubbles, are of the order of thickness of molten layer formed right after laser irradiation. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Electrons in the Field of Interfering Laser Pulses with Tilted Fronts: Formation of Compressed Bunches and Their Application for the Generation of Coherent γ – Rays
Authors: Korobkin V.V. , Romanovskiy M.Yu. , Shiryaev O.B. , Trofimov V.A. 
Published: December 2013

AbstractSimulations show that optical traps for charged particles can be formed in the fields of intense ultrashort laser pulses with tilted amplitude fronts. The traps travel in space with the velocities close to the speed of light and can be used for the creation of electron bunches which, at the laser intensities which are currently attainable, are compressed to proportions far below the laser wavelength and have energies reaching hundreds of GeV per particle. If an additional ultrashort laser pulse is propagated in the direction opposite to that of the bunch motion and interacts with the electrons, inverse Compton scattering occurs, with most of the electron energy being transferred to the resulting gamma‐quanta. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The safety of dipeptidyl peptidase‐4 (DPP‐4) inhibitors or sodium‐glucose cotransporter 2 (SGLT‐2) inhibitors added to metformin background therapy in patients with type 2 diabetes mellitus: a systematic review and meta‐analysis
Authors: Kawalec Paweł , Mikrut Alicja , Łopuch Sylwia 
Published: December 2013

SummaryThe aim of the present meta‐analysis was to assess the safety profile of dipeptidyl peptidase‐4 (DPP‐4) inhibitors and sodium‐glucose cotransporter 2 (SGLT‐2) inhibitors in comparison with placebo as add‐on to metformin therapy in patients with type 2 diabetes. Randomized controlled trials and controlled clinical trials were identified by searching Pubmed, Embase and the Cochrane Central Register of Controlled Trials database until 15 July 2013. All included studies were critically appraised and analysed with the use of Review Manager 5.1.0 software according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement protocol. Twenty randomized and double‐blinded studies published in 22 articles fulfilled the inclusion criteria for meta‐analysis. The overall results demonstrated that the use of oral antidiabetic agents (analysed separately and together) was not associated with any significantly increased risk of any serious adverse events including hypoglycaemia and gastrointestinal disorders. Moreover, the use of DPP‐4 or SGLT‐2 inhibitors significantly decreased risk of diarrhoea compared with placebo, when given concomitantly with metformin. However, we found that the SGLT‐2 inhibitors were more likely to cause a genital infection. Despite some limitations, the findings of this meta‐analysis indicate that DPP‐4 or SGLT‐2 inhibitors have favourable safety profile, and such therapy, when combined with metformin is well tolerated. Copyright © 2013 John Wiley & Sons, Ltd.
Incretins: Their physiology and application in the treatment of diabetes mellitus
Authors: Tasyurek Hale M. , Altunbas Hasan Ali , Balci Mustafa Kemal , Sanlioglu Salih 
Published: December 2013

SummaryTherapies targeting the action of incretin hormones have been under close scrutiny in recent years. The incretin effect has been defined as postprandial enhancement of insulin secretion by gut‐derived factors. Likewise, incretin mimetics and incretin effect amplifiers are the two different incretin‐based treatment strategies developed for the treatment of diabetes. Although, incretin mimetics produce effects very similar to those of natural incretin hormones, incretin effect amplifiers act by inhibiting dipeptidyl peptidase‐4 (DPP‐4) enzyme to increase plasma concentration of incretins and their biologic effects. Because glucagon‐like peptide‐1 (GLP‐1) is an incretin hormone with various anti‐diabetic actions including stimulation of glucose‐induced insulin secretion, inhibition of glucagon secretion, hepatic glucose production and gastric emptying, it has been evaluated as a novel therapeutic agent for the treatment of type 2 diabetes mellitus (T2DM). GLP‐1 also manifests trophic effects on pancreas such as pancreatic beta cell growth and differentiation. Because DPP‐4 is the enzyme responsible for the inactivation of GLP‐1, DPP‐4 inhibition represents another potential strategy to increase plasma concentration of GLP‐1 to enhance the incretin effect. Thus, anti‐diabetic properties of these two classes of drugs have stimulated substantial clinical interest in the potential of incretin‐based therapeutic agents as a means to control glucose homeostasis in T2DM patients. Despite this fact, clinical use of GLP‐1 mimetics and DPP‐4 inhibitors have raised substantial concerns owing to possible side effects of the treatments involving increased risk for pancreatitis, and C‐cell adenoma/carcinoma. Thus, controversial issues in incretin‐based therapies under development are reviewed and discussed in this manuscript. Copyright © 2013 John Wiley & Sons, Ltd.
Sesquiterpenes from Artemisia argyi: Absolute Configurations and Biological Activities
Authors: Wang Shu , Sun Jian , Zeng Kewu , Chen Xiaoguang , Zhou Wanqi , Zhang Chen , Jin Hongwei , Jiang Yong , Tu Pengfei 
Published: December 2013

AbstractNine guaiane‐type sesquiterpenes and one eudesmane‐type one – namely argyinolides A–J (1–10) – as well as nine known analogues were isolated from the leaves of Artemisia argyi Levl. et Vant. Their structures were determined by interpretation of spectroscopic data (MS, 1D and 2D NMR). A combination of X‐ray crystal diffraction, specific optical rotations, CD spectroscopy, ECD calculation, and Mosher ester methods was employed to resolve the absolute configurations of the isolated compounds. Biological investigations into their cytotoxicities and anti‐inflammatory effects showed that 1, 13, 16, and 18 were remarkably cytotoxic against Bel‐742 and/or A549 cells, with IC50 values of 3.3–6.0 μM, whereas 7, 11–13, 16, and 18 exhibited sound inhibitory activity on LPS‐stimulated NO production in BV‐2 microglial cells, with IC50 values ranging from 3.2 to 8.6 μM. In addition, a brief discussion on the applicability of Geissman's rule for the sesquiterpene lactones, the probable reason for the presence of chlorine‐containing sesquiterpenes, and preliminary structure–activity relationships (SARs) are included.
Synthesis of Pladienolide B and Its 7‐Epimer with Insights into the Role of the Allylic Acetate
Authors: Müller Sarah , Sasse Florenz , Maier Martin E. 
Published: December 2013

AbstractDiastereomeric macrolactones 41 and 48, which are epimeric at C‐7, were both prepared by a synthesis based on our previously developed route to the macrolactone core of pladienolide B. Both compounds contain all the functionality of the macrolactone core plus the vinyl iodide unit in the side chain. The key step to construct the seco acid for the macrolactonization was a Horner–Wadsworth–Emmons (HWE) reaction to produce acyclic enone 17. The required keto phosphonate for the HWE reaction was originally obtained from (R)‐(–)‐linalool. The derived macrolactone underwent a reduction of the enone function to give 7‐epi‐alcohol 20, and its acetylation, either under Mitsunobu or classical acylation conditions, produced allylic acetate 40. This represents a rare case in which a Mitsunobu reaction occurred with retention of configuration. The complete side chain that contains all the functionality was attached by a Stille cross‐coupling reaction to lead to 7‐epi‐pladienolide B (42). To obtain pladienolide B (1), the reduction of acyclic enone 17 under chelation‐controlled conditions [Zn(BH4)2, Et2O] gave allylic alcohol 43 with the correct configuration at C‐7 with regard to the natural product. Conversion of this allylic alcohol to seco acid 46 followed by a Shiina macrolactonization afforded vinyl iodide 48. Its Stille coupling with vinylstannane 39 provided pladienolide B (1). Preliminary testing for cytotoxicity against the L929 cell line showed 7‐epi‐pladienolide B (42) to be completely inactive, which is in contrast to pladienolide B (1) that displayed an IC50 (half maximal inhibitory concentration) value of 7.5 nM. These results point to the importance of the correct configuration of the OAc functional group at C‐7 of pladienolide B.
Toward improved drought tolerance in bioenergy crops: QTL for carbon isotope composition and stomatal conductance in Populus
Authors: Viger Maud , Rodriguez‐Acosta Maricela , Rae Anne M. , Morison James I. L. , Taylor Gail 
Published: December 2013

AbstractDedicated non‐food bioenergy crops like poplar are needed as sustainable, low‐input feedstocks for renewable energy in a future drier climate, where they can be grown on marginal soils. Such plants should have a low water, carbon, and chemical footprint. Capturing natural variation in traits associated with water use efficiency (WUE) is the first step to developing trees that require less water and may be adapted to drier environments. We have assessed stomatal conductance (gs) and leaf carbon isotope composition (δ13C, an indirect indicator of leaf WUE) in two Populus species, P. deltoides and P. trichocarpa and their F2 progeny, grown in the United Kingdom and in Italy. Populus deltoides leaves showed lower δ13C than P. trichocarpa, suggesting a higher WUE in P. trichocarpa, although without drought preconditioning, gs of P. trichocarpa was less responsive to dehydration and abscisic acid treatment than P. deltoides, suggesting that leaf anatomy may also contribute to δ13C in Populus. Quantitative trait loci (QTL) were identified for δ13C on eight linkage groups (LG) and two QTL for gs. From these. QTL and differential gene expression in response to drought from microarray data, we focused on three hotspots and identified 23 novel candidate genes on LG VI, X, and XVI. We have begun to unravel the genetic basis of WUE in bioenergy Populus revealing important underpinning data for breeding and improvement in poplar genotypes for a future drier climate.
Preparation and evaluation of PEO‐coated materials for a microchannel hemodialyzer
Authors: Heintz Keely , Schilke Karl F. , Snider Joshua , Lee Woo‐Kul , Truong Mitchell , Coblyn Matthew , Jovanovic Goran , McGuire Joseph 
Published: December 2013

AbstractThe marked increase in surface‐to‐volume ratio associated with microscale devices for hemodialysis leads to problems with hemocompatibility and blood flow distribution that are more challenging to manage than those encountered at the conventional scale. In this work stable surface modifications with pendant polyethylene oxide (PEO) chains were produced on polydimethylsiloxane (PDMS), polycarbonate microchannel, and polyacrylonitrile membrane materials used in construction of microchannel hemodialyzer test articles. PEO layers were prepared by radiolytic grafting of PEO‐polybutadiene‐PEO (PEO‐PB‐PEO) triblock polymers to the material surfaces. Protein repulsion was evaluated by measurement of surface‐bound enzyme activity following contact of uncoated and PEO‐coated surfaces with β‐galactosidase. Protein adsorption was decreased on PEO‐coated polycarbonate and PDMS materials to about 20% of the level recorded on the uncoated materials. Neither the triblocks nor the irradiation process was observed to have any effect on protein interaction with the polyacrylonitrile membrane, or its permeability to urea. This approach holds promise as a means for in situ application of safe, efficacious coatings to microfluidic devices for blood processing that will ensure good hemocompatibility and blood flow distribution, with no adverse effects on mass transfer. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 1014–1020, 2014.
Down‐Regulation of miR‐96 by Bone Morphogenetic Protein Signaling is Critical for Vascular Smooth Muscle Cell Phenotype Modulation
Authors: Kim Sunghwan , Hata Akiko , Kang Hara 
Published: December 2013

ABSTRACTThe bone morphogenetic protein (BMP) signaling pathway is critical for the induction and maintenance of contractile phenotype in vascular smooth muscle cells (VSMCs). Inactivation of BMP signaling is common in abnormalities in vascular development and in vascular proliferative conditions, such as pulmonary artery hypertension. Herein, we identify microRNA‐96 (miR‐96) as a modulator of the VSMC phenotype in response to BMP4 signaling. We show that miR‐96 is down‐regulated by BMP4 treatment, which results in the derepression of a novel target, Tribbles‐like protein 3 (Trb3). miR‐96 targets a partially complementary sequence localized in the 3′ UTR of Trb3. Trb3 is an essential positive regulator of the BMP signaling pathway and promotes contractile phenotype in VSMCs. In conclusion, our study demonstrates a novel mechanism of regulation of SMC‐specific gene expression and induction of a VSMC contractile phenotype by the BMP4 signaling pathway via suppression of the miR‐96‐Trb3 axis. J. Cell. Biochem. 115: 889–895, 2014. © 2013 Wiley Periodicals, Inc.
Heavy metals in agricultural landscapes as hazards to human and ecosystem health: a case study on zinc and cadmium in drainage channel sediments
Authors: Savic Radovan , Ondrasek Gabrijel , Josimov‐Dundjerski Jasmina 
Published: December 2013

AbstractBACKGROUNDIn agricultural systems, heavy metals pose severe risks to the health of soil–plant–animal–human continuum. Drainage channels, as integral components of agricultural landscapes, contain sediment material that can be both a source and a sink of metals and other toxic/persistent elements due to its highly reactive interfaces and strong binding affinity. The drainage channel network in a case study area of Vojvodina (Serbia) is not appropriately protected from contamination, nor is it maintained regularly (e.g. by desilting), thus endangering and potentially decreasing the ecological value of surrounding water and agricultural land resources, i.e. exposing food production to potential contaminants. In this study (2004–2012), Cd and Zn concentrations were analysed in 100 samples from 46 drainage channels sediments spread along the areas of the most intensive agricultural land use in Vojvodina.RESULTSAmong the samples measured, 5% had Cd and 14% had Zn concentrations above the maximally permitted levels, indicating that some drainage channel sections have been exposed to different point and non‐point source pollutants. The maximum detected concentrations of the analysed elements were >50% (Zn) and were as much as 11‐fold (Cd) higher than their remediation values.CONCLUSIONThere is a strong need for the establishment of qualitative monitoring of channel sediment media in agro‐ecosystems closely linked with complex pollution sources (intensive agriculture, industry, urban zones). © 2013 Society of Chemical Industry
Versatile and enhanced tumour modelling in mice via somatic cell transduction
Authors: Rodriguez Esther , Mannion Liz , D'Santos Paula , Griffiths Meryl , Arends Mark J , Brindle Kevin M , Lyons Scott K 
Published: December 2013

AbstractGenetically engineered mouse (GEM) models of cancer currently comprise the most accurate way to experimentally recapitulate the human disease in the laboratory. Given recent advances in genomics and genetic screens, however, as well as an increasing urgency for the translation of effective preclinical treatments into the clinic, there is a pressing need to make these models easier and more efficient to work with. Accordingly, we have developed a versatile lentivirus‐based approach to induce tumours from somatic cells of GEMs, add or subtract gene expression and render the tumours imageable from a simple breeding stock. The vectors deliver a tamoxifen‐inducible and self‐inactivating Cre recombinase, conditional bioluminescent and fluorescent proteins and an shRNA component. Following the transduction of somatic cells, tumours are initiated by Cre‐mediated recombination of the inherited floxed alleles. Self‐inactivation of Cre expression switches on the expression of luciferase, thereby rendering the recombined cells and resulting tumours bioluminescent. We demonstrate proof of concept of this approach by inducing bioluminescent lung tumours in conditional Kras and p53 mice. We also show that a variant vector expressing shRNA alters tumour growth dynamics and the histological grade associated with the inherited genotype. This approach comprises a versatile means to induce imageable and spontaneous tumour burden in mice. The vectors can be readily customized at the bench to modify reporter readout or tumour phenotype without additional transgenic strain development or breeding. They should also be useful for inducing imageable tumours in organs other than the lung, provided that the inherited conditional genotype is sufficiently penetrant. © 2013 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
The small heat‐shock protein αB‐crystallin is essential for the nuclear localization of Smad4: impact on pulmonary fibrosis
Authors: Bellaye Pierre‐Simon , Wettstein Guillaume , Burgy Olivier , Besnard Valérie , Joannes Audrey , Colas Julien , Causse Sébastien , Marchal‐Somme Joëlle , Fabre Aurélie , Crestani Bruno , Kolb Martin , Gauldie Jack , Camus Philippe , Garrido Carmen , Bonniaud Philippe 
Published: December 2013

AbstractIdiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by the proliferation of myofibroblasts and the accumulation of extracellular matrix (ECM) in the lungs. TGF‐β1 is the major profibrotic cytokine involved in IPF and is responsible for myofibroblast proliferation and differentiation and ECM synthesis. αB‐crystallin is constitutively expressed in the lungs and is inducible by stress, acts as a chaperone and is known to play a role in cell cytoskeleton architecture homeostasis. The role of αB‐crystallin in fibrogenesis remains unknown. The principal signalling pathway involved in this process is the Smad‐dependent pathway. We demonstrate here that αB‐crystallin is strongly expressed in fibrotic lung tissue from IPF patients and in vivo rodent models of pulmonary fibrosis. We also show that αB‐crystallin‐deficient mice are protected from bleomycin‐induced fibrosis. Similar protection from fibrosis was observed in αB‐crystallin KO mice after transient adenoviral‐mediated over‐expression of IL‐1β or TGF‐β1. We show in vitro in primary epithelial cells and fibroblasts that αB‐crystallin increases the nuclear localization of Smad4, thereby enhancing the TGF‐β1–Smad pathway and the consequent activation of TGF‐β1 downstream genes. αB‐crystallin over‐expression disrupts Smad4 mono‐ubiquitination by interacting with its E3–ubiquitin ligase, TIF1γ, thus limiting its nuclear export. Conversely, in the absence of αB‐crystallin, TIF1γ can freely interact with Smad4. Consequently, Smad4 mono‐ubiquitination and nuclear export are favoured and thus TGF‐β1–Smad4 pro‐fibrotic activity is inhibited. This study demonstrates that αB‐crystallin may be a key target for the development of specific drugs in the treatment of IPF or other fibrotic diseases. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.