bluuebunny/crossref_metadata_2025 huggingface dataset:
Diagnostic and Therapeutic Challenges of Intrahepatic Biliary Cystadenoma and Cystadenocarcinoma: A Report of 10 Cases and Review of the Literature
Authors: Fragulidis Georgios P. , Vezakis Antonios I. , Konstantinidis Christos G. , Chondrogiannis Konstantinos K. , Primetis Elias S. , Kondi-Pafiti Agathi , Polydorou Andreas A.
Published: November 2015

The objective of this study was to present our experience with intrahepatic biliary cystadenomas and cystadenocarcinomas in 10 patients surgically managed in our department. Intrahepatic biliary cystadenomas and cystadenocarcinomas are rare cystic tumors that are often misdiagnosed preoperatively as simple cysts or hydatid cysts. They recur after incomplete resection and entail a risk of malignant transformation to cystadenocarcinoma. A retrospective review was conducted of patients with histologically confirmed intrahepatic biliary cystadenomas and cystadenocarcinomas between August 2004 and February 2013 who were surgically managed in our department. A total of 10 patients, 9 female and 1 male (mean age, 50 years), with cystic liver were reviewed. The size of the cysts ranged between 3.5 and 16 cm (mean, 10.6). Five patients had undergone previous interventions elsewhere and presented with recurrences. Liver resections included 6 hepatectomies, 2 bisegmentectomies, 1 extended right hepatectomy, and 1 enucleation due to the central position and the large size of the lesion. Pathology reports confirmed R0 resections in all cases. All patients were alive after a median follow-up of 6 years (range, 1–10 years), and no recurrence was detected. Intrahepatic biliary cystadenoma and cystadenocarcinoma should be considered in differential diagnosis in patients with liver cystic tumors. Because of the high recurrence rate and difficult accurate preoperative diagnosis, formal liver resection is mandatory. Enucleation with free margins is an option and is indicated where resection is impossible.
Giant Splenic Artery Pseudoaneurysm: A Case Report and Literature Review
Authors: Yagmur Yusuf , Akbulut Sami , Gumus Serdar , Demircan Firat
Published: November 2015

Splenic artery aneurysms (SAAs) are the third most frequent intra-abdominal aneurysm, following abdominal aorta and iliac artery aneurysms. SAAs are classified according to their involvement of arterial wall layers: true aneurysms involve all 3 layers (intima, media, and adventitia), and pseudoaneurysms involve only one or two. Herein we present a new case of giant pseudo SAA. A 65-year-old female patient with a pancreatic mass and iron deficiency was referred to our clinic for further investigation. Abdominal ultrasonography, contrast-enhanced CT and magnetic resonance imaging showed a lesion resembling a subcapsular hemangioma in the spleen, and aneurysmatic dilation of the splenic artery with a diameter of >5 cm. The large size of the aneurysm and the clinical findings were indications for surgical treatment. The patient underwent en bloc resection of the spleen, distal pancreas, and aneurysmatic segment of the splenic artery. The patient remains complication-free 2 months after the operation. Spontaneous rupture is the most important life-threatening complications of giant SAAs. Therefore, all symptomatic patients with SAA should be treated, as well as asymptomatic patients with lesions ≥2 cm, who are pregnant or fertile, have portal hypertension, or are candidates for liver transplantation. Despite advances in endovascular techniques, conventional abdominal surgery remains the gold standard for treatment.
Are 3‐D coronal mass ejection parameters from single‐view observations consistent with multiview ones?
Authors: Lee Harim , Moon Y.‐J. , Na Hyeonock , Jang Soojeong , Lee Jae‐Ok
Published: November 2015

To prepare for when only single‐view observations are available, we have made a test whether the 3‐D parameters (radial velocity, angular width, and source location) of halo coronal mass ejections (HCMEs) from single‐view observations are consistent with those from multiview observations. For this test, we select 44 HCMEs from December 2010 to June 2011 with the following conditions: partial and full HCMEs by SOHO and limb CMEs by twin STEREO spacecraft when they were approximately in quadrature. In this study, we compare the 3‐D parameters of the HCMEs from three different methods: (1) a geometrical triangulation method, the STEREO CAT tool developed by NASA/CCMC, for multiview observations using STEREO/SECCHI and SOHO/LASCO data, (2) the graduated cylindrical shell (GCS) flux rope model for multiview observations using STEREO/SECCHI data, and (3) an ice cream cone model for single‐view observations using SOHO/LASCO data. We find that the radial velocities and the source locations of the HCMEs from three methods are well consistent with one another with high correlation coefficients (≥0.9). However, the angular widths by the ice cream cone model are noticeably underestimated for broad CMEs larger than 100° and several partial HCMEs. A comparison between the 3‐D CME parameters directly measured from twin STEREO spacecraft and the above 3‐D parameters shows that the parameters from multiview are more consistent with the STEREO measurements than those from single view.
Gold Nanobipyramid‐Supported Silver Nanostructures with Narrow Plasmon Linewidths and Improved Chemical Stability
Authors: Zhu Xingzhong , Zhuo Xiaolu , Li Qian , Yang Zhi , Wang Jianfang
Published: November 2015

Silver nanostructures with narrow plasmon linewidths and good chemical stability are strongly desired for plasmonic applications. Herein, a facile method is discussed for the preparation of Ag nanostructures with narrow plasmon linewidths and improved chemical stability through Ag overgrowth on monodispersed Au nanobipyramids. Structural evolution from bipyramid through rice to rod is observed, indicating that Ag atoms are preferentially deposited on the side surfaces of Au nanobipyramids. The resultant (Au nanobipyramid)@Ag nanostructures possess high size and shape uniformities, and much narrower plasmon linewidths than other Ag nanostructures. The spectral evolution of the supported Ag nanostructures is ascertained by both ensemble and single‐particle characterizations, together with electrodynamic simulations. Systematic measurements of the refractive index sensing characteristics indicate that Ag nanostructures in this study possess high index sensitivities and figure of merit (sensitivity divided by linewidth) values. Moreover, Ag nanostructures in this study exhibit greatly improved chemical stability. The superior sensing capability of Ag nanostructures in this study is further demonstrated by the detection of sulfide ions at a relatively low detection limit. Taken together, results of this study show that the Au‐nano­bipyramid‐supported Ag nanostructures will be an outstanding candidate for the design of ultrasensitive plasmonic sensing devices as well as for the development of other plasmon‐enabled technological applications.
α‐Arylation/Heteroarylation of Chiral α‐Aminomethyltrifluoroborates by Synergistic Iridium Photoredox/Nickel Cross‐Coupling Catalysis
Authors: El Khatib Mirna , Serafim Ricardo Augusto Massarico , Molander Gary A.
Published: November 2015

Direct access to complex, enantiopure benzylamine architectures using a synergistic iridium photoredox/nickel cross‐coupling dual catalysis strategy has been developed. New C(sp3)C(sp2) bonds are forged starting from abundant and inexpensive natural amino acids.
Iron‐Catalyzed Direct Diazidation for a Broad Range of Olefins
Authors: Yuan Yong‐An , Lu Deng‐Fu , Chen Yun‐Rong , Xu Hao
Published: November 2015

Reported herein is a new iron‐catalyzed diastereoselective olefin diazidation reaction which occurs at room temperature (1–5 mol % of catalysts and d.r. values of up to >20:1). This method tolerates a broad range of both unfunctionalized and highly functionalized olefins, including those that are incompatible with existing methods. It also provides a convenient approach to vicinal primary diamines as well as other synthetically valuable nitrogen‐containing building blocks which are difficult to obtain with alternative methods. Preliminary mechanistic studies suggest that the reaction may proceed through a new mechanistic pathway in which both Lewis acid activation and iron‐enabled redox‐catalysis are crucial for selective azido‐group transfer.
Probing the Lipid Annular Belt by Gas‐Phase Dissociation of Membrane Proteins in Nanodiscs
Authors: Marty Michael T. , Hoi Kin Kuan , Gault Joseph , Robinson Carol V.
Published: November 2015

Interactions between membrane proteins and lipids are often crucial for structure and function yet difficult to define because of their dynamic and heterogeneous nature. Here, we use mass spectrometry to demonstrate that membrane protein oligomers ejected from nanodiscs in the gas phase retain large numbers of lipid interactions. The complex mass spectra that result from gas‐phase dissociation were assigned using a Bayesian deconvolution algorithm together with mass defect analysis, allowing us to count individual lipid molecules bound to membrane proteins. Comparison of the lipid distributions measured by mass spectrometry with molecular dynamics simulations reveals that the distributions correspond to distinct lipid shells that vary according to the type of protein–lipid interactions. Our results demonstrate that nanodiscs offer the potential for native mass spectrometry to probe interactions between membrane proteins and the wider lipid environment.
Layered Electron Acceptors by Dimerization of Acenes End‐ Capped with 1,2,5‐Thiadiazoles
Authors: Xia Debin , Guo Xin , Chen Long , Baumgarten Martin , Keerthi Ashok , Müllen Klaus
Published: November 2015

Layered electron acceptors D1–4 equipped with terminal 1,2,5‐thiadiazole groups have been constructed using a one‐pot protocol of acene dimerization. Their molecular structures are determined using single‐crystal X‐ray diffraction analysis. Photophysical and electrochemical properties of these molecules present a marked dependence on conjugation length and molecular geometry. An aggregation‐induced emission peak and an intramolecular excimer emission (IEE) band were observed for D2 and D4, respectively. This work paves the way for the efficient synthesis of layered heteroacenes.
Visible‐Light Photoredox‐Catalyzed C−H Difluoroalkylation of Hydrazones through an Aminyl Radical/Polar Mechanism
Authors: Xu Pan , Wang Guoqiang , Zhu Yuchen , Li Weipeng , Cheng Yixiang , Li Shuhua , Zhu Chengjian
Published: November 2015

An unprecedented visible‐light‐induced direct C−H bond difluoroalkylation of aldehyde‐derived hydrazones was developed. This reaction represents a new way to synthesize substituted hydrazones. The salient features of this reaction include difluorinated hydrazone synthesis rather than classical amine synthesis, extremely mild reaction conditions, high efficiency, wide substrate scope, ease in further transformations of the products, and one‐pot syntheses. Mechanistic analyses and theoretical calculations indicate that this reaction is enabled by a novel aminyl radical/polar crossover mechanism, with the aminyl radical being oxidized into the corresponding aminyl cation through a single electron transfer (SET) process.
Plasmonic Surfaces for Cell Growth and Retrieval Triggered by Near‐Infrared Light
Authors: Giner‐Casares Juan J. , Henriksen‐Lacey Malou , García Isabel , Liz‐Marzán Luis M.
Published: November 2015

Methods for efficient detachment of cells avoiding damage are required in tissue engineering and regenerative medicine. We introduce a bottom–up approach to build plasmonic substrates using micellar block copolymer nanolithography to generate a 2D array of Au seeds, followed by chemical growth leading to anisotropic nanoparticles. The resulting plasmonic substrates show a broad plasmon band covering a wide part of the visible and near‐infrared (NIR) spectral ranges. Both human and murine cells were successfully grown on the substrates. A simple functionalization step of the plasmonic substrates with the cyclic arginylglycylaspartic acid (c‐RGD) peptide allowed us to tune the morphology of integrin‐rich human umbilical vein endothelial cells (HUVEC). Subsequent irradiation with a NIR laser led to highly efficient detachment of the cells with cell viability confirmed using the MTT assay. We thus propose the use of such plasmonic substrates for cell growth and controlled detachment using remote near‐IR irradiation, as a general method for cell culture in biomedical applications.
A Self‐Assembled Respiratory Chain that Catalyzes NADH Oxidation by Ubiquinone‐10 Cycling between Complex I and the Alternative Oxidase
Authors: Jones Andrew J. Y. , Blaza James N. , Bridges Hannah R. , May Benjamin , Moore Anthony L. , Hirst Judy
Published: November 2015

Complex I is a crucial respiratory enzyme that conserves the energy from NADH oxidation by ubiquinone‐10 (Q10) in proton transport across a membrane. Studies of its energy transduction mechanism are hindered by the extreme hydrophobicity of Q10, and they have so far relied on native membranes with many components or on hydrophilic Q10 analogues that partition into membranes and undergo side reactions. Herein, we present a self‐assembled system without these limitations: proteoliposomes containing mammalian complex I, Q10, and a quinol oxidase (the alternative oxidase, AOX) to recycle Q10H2 to Q10. AOX is present in excess, so complex I is completely rate determining and the Q10 pool is kept oxidized under steady‐state catalysis. The system was used to measure a fully‐defined KM value for Q10. The strategy is suitable for any enzyme with a hydrophobic quinone/quinol substrate, and could be used to characterize hydrophobic inhibitors with potential applications as pharmaceuticals, pesticides, or fungicides.
Practical Organocatalytic Synthesis of Functionalized Non‐C2‐Symmetrical Atropisomeric Biaryls
Authors: Gao Hongyin , Xu Qing‐Long , Keene Craig , Yousufuddin Muhammed , Ess Daniel H. , Kürti László
Published: November 2015

An organic acid catalyzed direct arylation of aromatic C(sp2)H bonds in phenols and naphthols for the preparation of 1,1′‐linked functionalized biaryls was developed. The products are non‐C2‐symmetrical, atropoisomeric, and represent previously untapped chemical space. Overall this transformation is operationally simple, does not require an external oxidant, is readily scaled up (up to 98 mmol), and the structurally diverse 2,2′‐dihydroxy biaryl (i.e., BINOL‐type), as well as 2‐amino‐2′‐hydroxy products (i.e., NOBIN‐type) are formed with complete regioselectivity. Density‐functional calculations suggest that the quinone and imino‐quinone monoacetal coupling partners are exclusively arylated at their α‐position by an asynchronous [3,3]‐sigmatropic rearrangement of a mixed acetal species which is formed in situ under the reaction conditions.
Three‐dimensional Carbon Nitride/Graphene Framework as a High‐Performance Cathode for Lithium‐Ion Batteries
Authors: Huang Yanshan , Tang Yanping , Mai Yiyong , Wang Xinjing , Wang Chi , Han Sheng , Zhang Fan , Wu Dongqing , Feng Xinliang
Published: November 2015

A three‐dimensional polymeric carbon nitride/graphene framework (CN/GF) was fabricated by the ionic self‐assembly of graphene oxide and protonated polymeric carbon nitride nanosheets. As the cathode material in lithium‐ion batteries, CN/GF showed an excellent reversible capacity of 184 mA h g−1 at 0.05 A g−1 for 150 cycles and maintained the capacity of 60 mA h g−1 at 5 A g−1.
De Novo Design of Xeno‐Metallo Coiled Coils
Authors: Slope Louise N. , Peacock Anna F. A.
Published: November 2015

Bioinorganic chemists aspire to achieve the same exquisite and highly controlled inorganic chemistry featured in biology. An exciting mimetic approach involves the use of miniature artificial protein scaffolds designed de novo (often based on the coiled coil (CC) scaffold), for reproducing native metal ion sites and their function. Recently, there is increased interest, instead, in the design of xeno‐metal sites within CC assemblies. This involves incorporating either non‐biological metal ions, cofactors or non‐proteinogenic amino acid ligands for metal ion coordination, whilst retaining a minimal CC protein scaffold. Using this approach, one should be able to create functional designs with unique and unusual properties, which combine the advantages of both biology and ‘traditional’ non‐biological inorganic chemistry. It is the recent progress with respect to the design of xeno‐metallo CCs which will be discussed in this Focus Review.
Expression, purification, and characterization of mouse nesfatin‐1 in Escherichia coli
Authors: Xiao Chunlan , Liu Junyi , Tang Yanchun , Chen Junyong , Wu Xiaopeng , Bi Feng , Zhang Jing
Published: November 2015

Nesfatin‐1 is a newly discovered satiety molecule expressed mainly in the hypothalamic nuclei. It suppresses both short‐term and long‐term appetite. Six synthetic deoxyoligonucleotides overlapped by PCR encoding nesfatin‐1 were cloned into a pET28a vector after the hexa‐histidine‐tagged multiple cloning sites sequence with an enterokinase recognition site incorporated in‐between. The recombinant plasmid was transformed into Escherichia coli strain Rosetta to express the fusion protein, which constituted 27% of the total cell proteins. After purified by Ni‐sepharose affinity chromatography, the fusion protein was treated with enterokinase to release nesfatin‐1. The nesfatin‐1 sample was further purified with reverse‐phase high performance liquid chromatography (HPLC), and its molecular weight was determined by mass spectrometry. The biological activities of recombinant nesfatin‐1 were also assessed using in vivo animal models. The method described here promises to produce about 8 mg biologically active nesfatin‐1 with homogeneity over 98% from 1‐L shaking flask culture of E. coli, which can be considered as an easy and cost‐effective way to synthesize nesfatin‐1.
Optimization of thermophilic trans‐isoprenyl diphosphate synthase expression in Escherichia coli by response surface methodology
Authors: Piccolomini Angelica A. , Fiabon Alex , Borrotti Matteo , De Lucrezia Davide
Published: November 2015

We optimized the heterologous expression of trans‐isoprenyl diphosphate synthase (IDS), the key enzyme involved in the biosynthesis of trans‐polyisoprene. trans‐Polyisoprene is a particularly valuable compound due to its superior stiffness, excellent insulation, and low thermal expansion coefficient. Currently, trans‐polyisoprene is mainly produced through chemical synthesis and no biotechnological processes have been established so far for its large‐scale production. In this work, we employed D‐optimal design and response surface methodology to optimize the expression of thermophilic enzymes IDS from Thermococcus kodakaraensis. The design of experiment took into account of six factors (preinduction cell density, inducer concentration, postinduction temperature, salt concentration, alternative carbon source, and protein inhibitor) and seven culture media (LB, NZCYM, TB, M9, Ec, Ac, and EDAVIS) at five different pH points. By screening only 109 experimental points, we were able to improve IDS production by 48% in close‐batch fermentation.
Reactivity Controlling Factors for an Aromatic Carbon‐Centered σ,σ,σ‐Triradical: The 4,5,8‐Tridehydroisoquinolinium Ion
Authors: Vinueza Nelson R. , Jankiewicz Bartłomiej J. , Gallardo Vanessa A. , LaFavers Gregory Z. , DeSutter Dane , Nash John J. , Kenttämaa Hilkka I.
Published: November 2015

The chemical properties of the 4,5,8‐tridehydroisoquinolinium ion (doublet ground state) and related mono‐ and biradicals were examined in the gas phase in a dual‐cell Fourier‐transform ion cyclotron resonance (FT‐ICR) mass spectrometer. The triradical abstracted three hydrogen atoms in a consecutive manner from tetrahydrofuran (THF) and cyclohexane molecules; this demonstrates the presence of three reactive radical sites in this molecule. The high (calculated) electron affinity (EA=6.06 eV) at the radical sites makes the triradical more reactive than two related monoradicals, the 5‐ and 8‐dehydroisoquinolinium ions (EA=4.87 and 5.06 eV, respectively), the reactivity of which is controlled predominantly by polar effects. Calculated triradical stabilization energies predict that the most reactive radical site in the triradical is not position C4, as expected based on the high EA of this radical site, but instead position C5. The latter radical site actually destabilizes the 4,8‐biradical moiety, which is singlet coupled. Indeed, experimental reactivity studies show that the radical site at C5 reacts first. This explains why the triradical is not more reactive than the 4‐dehydroisoquinolinium ion because the C5 site is the intrinsically least reactive of the three radical sites due to its low EA. Although both EA and spin–spin coupling play major roles in controlling the overall reactivity of the triradical, spin–spin coupling determines the relative reactivity of the three radical sites.
Gold‐ or Silver‐Catalyzed Syntheses of Pyrones and Pyridine Derivatives: Mechanistic and Synthetic Aspects
Authors: Preindl Johannes , Jouvin Kévin , Laurich Daniel , Seidel Günter , Fürstner Alois
Published: November 2015

3‐Oxo‐5‐alkynoic acid esters, on treatment with a carbophilic catalyst, undergo 6‐endo‐dig cyclization reactions to furnish either 2‐pyrones or 4‐pyrones in high yields. The regiochemical course can be dialed in by the proper choice of the alcohol part of the ester and the π‐acid. This transformation is compatible with a variety of acid‐sensitive groups as witnessed by a number of exigent applications to the total synthesis of natural products, including pseudopyronine A, hispidine, phellinin A, the radininol family, neurymenolide, violapyrone, wailupemycin and an unnamed brominated 4‐pyrone of marine origin. Although the reaction proceeds well in neutral medium, the rate is largely increased when HOAc is used as solvent or co‐solvent, which is thought to favor the protodeauration of the reactive alkenyl‐gold intermediates as the likely rate‐determining step of the catalytic cycle. Such intermediates are prone to undergo diauration as an off‐cycle event that sequesters the catalyst; this notion is consistent with literature data and supported by the isolation of the gem‐diaurated complexes 12 and 15. Furthermore, silver catalysis allowed access to be gained to 2‐alkoxypyridine and 2‐alkoxyisoquinoline derivatives starting from readily available imidate precursors.
Dual Lewis Acid/Lewis Base Catalyzed Acylcyanation of Aldehydes: A Mechanistic Study
Authors: Laurell Nash Anna , Hertzberg Robin , Wen Ye‐Qian , Dahlgren Björn , Brinck Tore , Moberg Christina
Published: November 2015

A mechanistic investigation, which included a Hammett correlation analysis, evaluation of the effect of variation of catalyst composition, and low‐temperature NMR spectroscopy studies, of the Lewis acid–Lewis base catalyzed addition of acetyl cyanide to prochiral aldehydes provides support for a reaction route that involves Lewis base activation of the acyl cyanide with formation of a potent acylating agent and cyanide ion. The cyanide ion adds to the carbonyl group of the Lewis acid activated aldehyde. O‐Acylation by the acylated Lewis base to form the final cyanohydrin ester occurs prior to decomplexation from titanium. For less reactive aldehydes, the addition of cyanide is the rate‐determining step, whereas, for more reactive, electron‐deficient aldehydes, cyanide addition is rapid and reversible and is followed by rate‐limiting acylation. The resting state of the catalyst lies outside the catalytic cycle and is believed to be a monomeric titanium complex with two alcoholate ligands, which only slowly converts into the product.
From an Isolable Acyclic Phosphinosilylene Adduct to Donor‐Stabilized SiE Compounds (E=O, S, Se)
Authors: Hansen Kerstin , Szilvási Tibor , Blom Burgert , Irran Elisabeth , Driess Matthias
Published: November 2015

Reaction of the arylchlorosilylene‐NHC adduct ArSi(NHC)Cl [Ar=2,6‐Trip2C6H3; NHC=(MeC)2(NMe)2C:] 1 with one molar equiv of lithium diphenylphosphanide affords the first stable NHC‐stabilized acyclic phosphinosilylene adduct 2 (ArSi(NHC)PPh2), which could be structurally characterized. Compound 2, when reacted with one molar equiv selenium and sulfur, affords the silanechalcogenones 4 a and 4 b (ArSi(NHC)(E)PPh2, 4 a: E=Se, 4 b: E=S), respectively. Conversion of 2 with an excess of Se and S, through additional insertion of one chalcogen atom into the SiP bond, leads to 3 a and 3 b (ArSi(NHC)(E)‐E‐P(E)Ph2, 3 a: E=Se, 3 b: E=S), respectively. Additionally, the exposure of 2 to N2O or CO2 yielded the isolable NHC‐stabilized silanone 4 c, Ar(NHC)(Ph2P)SiO.
Fluid dynamics study of the flow and pressure drop analysis of a non‐Newtonian fluid through annular ducts with unusual cross‐sections
Authors: Bicalho Isabele Cristina , Mognon José Lucas , Ataíde Carlos Henrique , Duarte Claudio Roberto
Published: November 2015

This paper concerns an experimental and computational study of the laminar flow developed by a pseudoplastic fluid through a partially‐obstructed annulus, considering the effects of eccentricity and inner cylinder rotation. For the eccentric cases the eccentric rotation of the inner tube is applied, which is a novelty in the literature. Pressure drop experimental data are reported for flows of 3 and 9 m3/h of a 1 mg/g xanthan gum aqueous solution through a concentric and a 46 % eccentric annulus with partial obstruction of 6 mm, for cases with and without rotation of the inner cylinder (0 and 400 rpm). Numerical simulations were performed using computational fluid dynamics (CFD) techniques which allowed for reporting of axial velocity profiles, apparent viscosity distribution, and pressure drops for a range of eccentricity values (0, 23, and 46 %) and obstruction heights (0, 6, and 12 mm), which were systematically compared for cases with and without rotation of the inner tube (0 and 400 rpm). Comparisons between numerical calculations and the flow data indicated, in general, very close agreement. Eccentric rotation of the inner cylinder presented a distortion effect on the axial velocity and apparent viscosity profiles for the high eccentricity case (46 %) with high obstruction (12 mm), where two maxima regions were observed, one of them near the inner cylinder.
The Molecular Basis for Dual Fatty Acid Amide Hydrolase (FAAH)/Cyclooxygenase (COX) Inhibition
Authors: Palermo Giulia , Favia Angelo D. , Convertino Marino , De Vivo Marco
Published: November 2015

The design of multitarget‐directed ligands is a promising strategy for discovering innovative drugs. Here, we report a mechanistic study that clarifies key aspects of the dual inhibition of the fatty acid amide hydrolase (FAAH) and the cyclooxygenase (COX) enzymes by a new multitarget‐directed ligand named ARN2508 (2‐[3‐fluoro‐4‐[3‐(hexylcarbamoyloxy)phenyl]phenyl]propanoic acid). This potent dual inhibitor combines, in a single scaffold, the pharmacophoric elements often needed to block FAAH and COX, that is, a carbamate moiety and the 2‐arylpropionic acid functionality, respectively. Molecular modeling and molecular dynamics simulations suggest that ARN2508 uses a noncovalent mechanism of inhibition to block COXs, while inhibiting FAAH via the acetylation of the catalytic Ser241, in line with previous experimental evidence for covalent FAAH inhibition. This study proposes the molecular basis for the dual FAAH/COX inhibition by this novel hybrid scaffold, stimulating further experimental studies and offering new insights for the rational design of novel anti‐inflammatory agents that simultaneously act on FAAH and COX.
Reversible Photoisomerization of Spiropyran on the Surfaces of Au25 Nanoclusters
Authors: Udayabhaskararao T. , Kundu Pintu K. , Ahrens Johannes , Klajn Rafal
Published: November 2015

Au25 nanoclusters functionalized with a spiropyran molecular switch are synthesized via a ligand‐exchange reaction at low temperature. The resulting nanoclusters are characterized by optical and NMR spectroscopies as well as by mass spectrometry. Spiropyran bound to nanoclusters isomerizes in a reversible fashion when exposed to UV and visible light, and its properties are similar to those of free spiropyran molecules in solution. The reversible photoisomerization entails the modulation of fluorescence as well as the light‐controlled self‐assembly of nanoclusters.
Phase‐selective Route to V‐O Film Formation: A Systematic MOCVD Study Into the Effects of Deposition Temperature on Structure and Morphology
Authors: Spanò Simon F. , Toro Roberta G. , Condorelli Guglielmo G. , Messina Grazia M. L. , Marletta Giovanni , Malandrino Graziella
Published: November 2015

A systematic study into the MOCVD of V‐O films using the vanadyl‐acetylacetonate [VO(acac)2] precursor is carried out. The films are prepared via low pressure MOCVD on Si(001) substrates. The nature and quality of films are examined by varying operational parameters, e.g., deposition temperature, precursor vaporization rate, and flow of oxygen reacting gas. X‐ray diffraction data point to the formation of crystalline films in the range 200−550 °C. Outside of this temperature ranges amorphous phases were obtained. Field‐emission scanning electron microscope (FESEM) images indicate very homogeneous surfaces with grain shape and dimensions depending on operational conditions. Energy dispersive X‐ray (EDX) and X‐ray photoelectron spectroscopy (XPS) analyses point to the absence of any C contamination.
The history of efforts to regulate dietary supplements in the USA
Authors: Swann John P.
Published: November 2015

This review examines the emergence of dietary supplements and how the Food and Drug Administration (FDA) attempted to regulate these, beginning with the arrival of vitamins and how these were managed under the 1906 Food and Drugs Act, and ending with the seismic influence of the 1994 Dietary Supplement Health and Education Act (DSHEA). Included are the impact of major laws, key court decisions, and the construction of the FDA's supplement actions and rules from the 1920s to the 1990s for products that were neither drugs nor typical foods. Stiff resistance to the regulations by supplement manufacturers, trade associations, politicians, and especially the public at large is an important part of this story. The paper closes with the passage of DSHEA and how it literally changed the definition and parameters of control of dietary supplements. Copyright © 2015 John Wiley & Sons, Ltd.
Should states and local governments regulate dietary supplements?
Authors: Starr Ranjani
Published: November 2015

Federal regulation of dietary supplements in the United States is governed by the Dietary Supplement Health and Education Act of 1994. The law has been criticized as weak and ineffective. Alarming research has emerged demonstrating that supplements may be mislabelled, contaminated, adulterated with dangerous or unknown compounds, or sold at toxic doses. As a result, the health community has raised concerns about the safety and quality of dietary supplements. Increased federal oversight is an important avenue for improving supplement safety; however, states and local governments may also pursue strategies to strengthen the overall regulatory control of dietary supplements. States and local governments have substantial experience in regulating other products that pose a risk to public health, such as tobacco. Additionally, much has been learned about the tactics the tobacco industry has employed to protect its interests. Lessons learned may be applied to new regulatory efforts aimed at improving the safety of dietary supplements at the state and local levels. Copyright © 2015 John Wiley & Sons, Ltd.
Functionalization of Highly Substituted 2,2′:6′,2″‐Terpyridine Derivatives
Authors: Hommes Paul , Reissig Hans‐Ulrich
Published: November 2015

On the basis of an easy access to 2,2′:6′,2″‐terpyridine derivatives bearing 6‐ and 6″‐methyl groups, the functionalization of these substituents was investigated. The direct oxidation or bromination of the methyl groups was not feasible on larger scale; however, a two‐step process employing oxidation to the pyridine N‐oxides followed by acetic anhydride promoted rearrangement (Boekelheide reaction) furnished the corresponding terpyridine derivatives with 6‐ and 6″‐acetoxymethyl groups in reasonable overall yields. These are excellent precursors for the synthesis of tetra‐ and pentadentate ligands, as demonstrated by several examples. This approach allowed access to a library of new functionalized 2,2′:6′,2″‐terpyridine derivatives.
Biotechnological production of ethanol: Biochemistry, processes and technologies
Authors: Sarris Dimitris , Papanikolaou Seraphim
Published: November 2015

The majority of environmental problems arise from the use of conventional energy sources. The liability of such problems along with the reduction of fossil energy resources has led to the global need for alternative renewable energy sources. Using renewable biofuels as energy sources is of remarkable and continuously growing importance. Producing bioethanol through conversion of waste and residual biomass can be a viable and important perspective. In the first part of this review, general concepts, approaches and considerations concerning the utilization of the most important liquid biofuels, namely biodiesel and bioethanol, are presented. Unlike biodiesel (specifically first generation biodiesel), the production of bioethanol is exclusively based on the utilization of microbial technology and fermentation engineering. In the second part of this review, the biochemistry of ethanol production, with regards to the use of hexoses, pentoses or glycerol as carbon sources, is presented and critically discussed. Differences in the glycolytic pathways between the major ethanol‐producing strains (Saccharomyces cerevisiae and Zymomonas mobilis) are presented. Regulation between respiration and fermentation in ethanol‐producing yeasts, viz. effects “Pasteur”, “Crabtree”, “Kluyver” and “Custers”, is discussed. Xylose and glycerol catabolism related with bioethanol production is also depicted and commented. The technology of the fermentation is presented along with a detailed illustration of the substrates used in the process and in pretreatment of lignocellulosic biomass, and the various fermentation configurations employed (separate hydrolysis and fermentation, simultaneous saccharification and fermentation, simultaneous saccharification and co‐fermentation and consolidated bioprocessing). Finally, the production of bioethanol under non‐aseptic conditions is presented and discussed.
On Forecasting Conflict in the Sudan: 2009–2012
Authors: Bessler David A. , Kibriya Shahriar , Chen Junyi , Price Edwin
Published: November 2015

This paper considers univariate and multivariate models to forecast monthly conflict events in the Sudan over the out‐of‐sample period 2009–2012. The models used to generate these forecasts were based on a specification from a machine learning algorithm fit to 2000–2008 monthly data. The model that includes previous month's wheat price performs better than a similar model which does not include past wheat prices (the univariate model). Both models did not perform well in forecasting conflict in a neighborhood of the 2012 ‘Heglig crisis’. Copyright © 2015 John Wiley & Sons, Ltd.
Procedure of brewing alcohol as a staple food: case study of the fermented cereal liquor “Parshot” as a staple food in Dirashe special woreda, southern Ethiopia
Authors: Sunano Yui
Published: November 2015

For most brews, alcohol fermentation and lactic fermentation take place simultaneously during the brewing process, and alcohol fermentation can progress smoothly because the propagation of various microorganisms is prevented by lactic fermentation. It is not necessary to cause lactic fermentation with a thing generated naturally and intentionally. The people living in the Dirashe area in southern Ethiopia drink three types of alcoholic beverages that are prepared from cereals. From these alcoholic beverages, parshot is prepared by the addition of plant leaves for lactic fermentation and nech chaka by adding cereal powder for lactic fermentation before alcohol fermentation. People living in the Dirashe area partake of parshot as part of their staple diet. The brewing process used for parshot and a food culture with alcoholic beverages as parts of the staple diet are rare worldwide. This article discusses the significance of using lactic fermentation before alcoholic fermentation and focuses on lactic fermentation in the brewing methods used for the three kinds of alcoholic beverages consumed in the Dirashe area. We initially observed the brewing process and obtained information about the process from the people in that area. Next, we determined the pH and analyzed the lactic acid (g/100 g) and ethanol (g/100 g) content during lactic fermentation of parshot and nech chaka; the ethyl acetate (mg/100 g) and volatile base nitrogen (mg/100 g) content during this period was also analyzed. In addition, we compared the ethanol (g/100 g) content of all three kinds of alcoholic beverages after completion of brewing. The results showed that it was possible to consume large quantities of these alcoholic beverages because of the use of lactic fermentation before alcoholic fermentation, which improved the safety and preservation characteristics of the beverages by preventing the propagation of various microorganisms, improving flavor, and controlling the alcohol level.
The development of brain network architecture
Authors: Wierenga Lara M. , van den Heuvel Martijn P. , van Dijk Sarai , Rijks Yvonne , de Reus Marcel A. , Durston Sarah
Published: November 2015

Brain connectivity shows protracted development throughout childhood and adolescence, and, as such, the topology of brain networks changes during this period. The complexity of these changes with development is reflected by regional differences in maturation. This study explored age‐related changes in network topology and regional developmental patterns during childhood and adolescence. We acquired two sets of Diffusion Weighted Imaging‐scans and anatomical T1‐weighted scans. The first dataset included 85 typically developing individuals (53 males; 32 females), aged between 7 and 23 years and was acquired on a Philips Achieva 1.5 Tesla scanner. A second dataset (N = 38) was acquired on a different (but identical) 1.5 T scanner and was used for independent replication of our results. We reconstructed whole brain networks using tractography. We operationalized fiber tract development as changes in mean diffusivity and radial diffusivity with age. Most fibers showed maturational changes in mean and radial diffusivity values throughout childhood and adolescence, likely reflecting increasing white matter integrity. The largest age‐related changes were observed in association fibers within and between the frontal and parietal lobes. Furthermore, there was a simultaneous age‐related decrease in average path length (P < 0.0001), increase in node strength (P < 0.0001) as well as network clustering (P = 0.001), which may reflect fine‐tuning of topological organization. These results suggest a sequential maturational model where connections between unimodal regions strengthen in childhood, followed by connections from these unimodal regions to association regions, while adolescence is characterized by the strengthening of connections between association regions within the frontal and parietal cortex. Hum Brain Mapp 37:717–729, 2016. © 2015 Wiley Periodicals, Inc.
Time scale effect and uncertainty in reconstruction of paleo‐hydrology
Authors: Razavi Saman , Elshorbagy Amin , Wheater Howard , Sauchyn David
Published: November 2015

Tree‐ring‐based reconstructions of paleo‐hydrology have proved useful for better understanding the irregularities and extent of past climate changes, and therefore, for more effective water resources management. Despite considerable advances in the field, there still exist challenges that introduce significant uncertainties into paleo‐reconstructions. This study outlines these challenges and address them by developing two themes: (1) the effect of temporal scaling on the strength of the relationship between the hydrologic variables, streamflow in this study, and tree growth rates and (2) the reconstruction uncertainty of streamflow due to the dissimilarity or inconsistency in the pool of tree‐ring chronologies (predictors in reconstruction) in a basin. Based on the insight gained, a methodology is developed to move beyond only relying on the annual hydrology‐growth correlations, and to utilize additional information embedded in the annual time series at longer time scales (e.g. multi‐year to decadal time scales). This methodology also generates an ensemble of streamflow reconstructions to formally account for uncertainty in the pool of chronology sites. The major headwater tributaries of the Saskatchewan River Basin, the main source of surface water in the Canadian Prairie Provinces, are used as the case study. It is shown that the developed methodology explains the variance of streamflows to a larger extent than the conventional approach and better preserves the persistence and variability of streamflows across time scales (Hurst‐type behaviour). The resulting ensemble of paleo‐hydrologic time series is able to more credibly pinpoint the timing and extent of past dry and wet periods and provides a dynamic range of uncertainty in reconstruction. This range varies with time over the course of the reconstruction period, indicating that the utility of tree‐ring chronologies for paleo‐reconstruction differs for different time periods over the past several centuries in the history of the region. The proposed ensemble approach provides a credible range of multiple‐century‐long water availability scenarios that can be used for vulnerability assessment of the existing water infrastructure and improving water resources management. Copyright © 2015 John Wiley & Sons, Ltd.
Extrapolation of acute toxicity across bee species
Authors: Thompson Helen
Published: November 2015

In applying cross-species extrapolation safety factors from honeybees to other bee species, some basic principles of toxicity have not been included, for example, the importance of body mass in determining a toxic dose. The present study re-analyzed published toxicity data, taking into account the reported mass of the individuals in the identified species. The analysis demonstrated a shift to the left in the distribution of sensitivity of honeybees relative to 20 other bee species when body size is taken into account, with the 95th percentile for contact and oral toxicity reducing from 10.7 (based on μg/individual bee) to 5.0 (based on μg/g bodyweight). Such an approach results in the real drivers of species differences in sensitivity—such as variability in absorption, distribution, metabolism, and excretion in and target–receptor binding—being more realistically reflected in the revised safety factor. Body mass can also be used to underpin the other parameter of first-tier risk assessment, that is, exposure. However, the key exposure factors that cannot be predicted from bodyweight are the effects of ecology and behavior of the different species on exposure to a treated crop. Further data are required to understand the biology of species associated with agricultural crops and the potential consequences of effects on individuals at the levels of the colony or bee populations. This information will allow the development of appropriate higher-tier refinement of risk assessments and testing strategies rather than extensive additional toxicity testing at Tier 1. Integr Environ Assess Manag 2016;12:622–626. © 2015 SETAC
Serum folate receptor alpha as a biomarker for ovarian cancer: Implications for diagnosis, prognosis and predicting its local tumor expression
Authors: Kurosaki Akira , Hasegawa Kosei , Kato Tomomi , Abe Kenji , Hanaoka Tatsuya , Miyara Akiko , O'Shannessy Daniel J. , Somers Elizabeth B. , Yasuda Masanori , Sekino Tetsuo , Fujiwara Keiichi
Published: November 2015

Folate receptor alpha (FRA) is a GPI‐anchored glycoprotein and encoded by the FOLR1 gene. High expression of FRA is observed in specific malignant tumors of epithelial origin, including ovarian cancer, but exhibits very limited normal tissue expression, making it as an attractive target for the ovarian cancer therapy. FRA is known to shed from the cell surface into the circulation which allows for its measurement in the serum of patients. Recently, methods to detect the soluble form of FRA have been developed and serum FRA (sFRA) is considered a highly promising biomarker for ovarian cancer. We prospectively investigated the levels of sFRA in patients clinically suspected of having malignant ovarian tumors. A total of 231 patients were enrolled in this study and analyzed for sFRA as well as tumor expression of FRA by immunohistochemistry. High sFRA was predominantly observed in epithelial ovarian cancer patients, but not in patients with benign or borderline gynecological disease or metastatic ovarian tumors from advanced colorectal cancers. Levels of sFRA were highly correlated to clinical stage, tumor grade and histological type and demonstrated superior accuracy for the detection of ovarian cancer than did serum CA125. High sFRA was significantly associated with shorter progression‐free survival in both early and advanced ovarian cancer patients. Finally, tumor FRA expression status was strongly correlated with sFRA levels. Taken together, these data suggest that sFRA might be a useful noninvasive serum biomarkers for future clinical trials assessing FRA‐targeted therapy.
CD90+ stromal cells are the major source of IL‐6, which supports cancer stem‐like cells and inflammation in colorectal cancer
Authors: Huynh Phuong T. , Beswick Ellen J. , Coronado Yun A. , Johnson Paul , O'Connell Malaney R. , Watts Tammara , Singh Pomila , Qiu Suimin , Morris Katherine , Powell Don W. , Pinchuk Irina V.
Published: November 2015

IL‐6 is a pleiotropic cytokine increased in CRC and known to directly promote tumor growth. Colonic myofibroblasts/fibroblasts (CMFs or stromal cells) are CD90+ innate immune cells representing up to 30% of normal colonic mucosal lamina propria cells. They are expanded in CRC tumor stroma, where they also known as a cancer associated fibroblasts (CAFs). Cells of mesenchymal origin, such as normal myofibroblasts/fibroblasts, are known to secrete IL‐6; however, their contribution to the increase in IL‐6 in CRC and to tumor‐promoting inflammation is not well defined. Using in situ, ex vivo and coculture analyses we have demonstrated that the number of IL‐6 producing CMFs is increased in CRC (C‐CMFs) and they represent the major source of IL‐6 in T2‐T3 CRC tumors. Activity/expression of stem cell markers‐aldehyde dehydrogenase and LGR5‐ was significantly up‐regulated in colon cancer cells (SW480, Caco‐2 or HT29) cultured in the presence of conditioned medium from tumor isolated C‐CMFs in an IL‐6 dependent manner. C‐CMF and its derived condition medium, but not normal CMF isolated from syngeneic normal colons, induced differentiation of tumor promoting inflammatory T helper 17 cells (Th17) cell responses in an IL‐6 dependent manner. Our study suggests that CD90+ fibroblasts/myofibroblasts may be the major source of IL‐6 in T2‐T3 CRC tumors, which supports the stemness of tumor cells and induces an immune adaptive inflammatory response (a.k.a. Th17) favoring tumor growth. Taken together our data supports the notion that IL‐6 producing CAFs (a.k.a. C‐CMFs) may provide a useful target for treating or preventing CRCs.