bluuebunny/crossref_metadata_2025 huggingface dataset:
Liposome‐Loaded Cell Backpacks
Authors: Polak Roberta , Lim Rosanna M. , Beppu Marisa M. , Pitombo Ronaldo N. M. , Cohen Robert E. , Rubner Michael F.
Published: November 2015

Cell backpacks, or micron‐scale patches of a few hundred nanometers in thickness fabricated by layer‐by‐layer (LbL) assembly, are potentially useful vehicles for targeted drug delivery on the cellular level. In this work, echogenic liposomes (ELIPs) containing the anticancer drug doxorubicin (DOX) are embedded into backpacks through electrostatic interactions and LbL assembly. Poly(allylamine hydrochloride)/poly(acrylic acid) (PAH/PAA)n, and poly(diallyldimethylammonium chloride)/poly(styrene sulfonate) (PDAC/SPS)n film systems show the greatest ELIP incorporation of the films studied while maintaining the structural integrity of the vesicles. The use of ELIPs for drug encapsulation into backpacks facilitates up to three times greater DOX loading compared to backpacks without ELIPs. Cytotoxicity studies reveal that monocyte backpack conjugates remain viable even after 72 h, demonstrating promise as drug delivery vehicles. Because artificial vesicles can load many different types of drugs, ELIP containing backpacks offer a unique versatility for broadening the range of possible applications for cell backpacks.
Highly Ordered Dual Porosity Mesoporous Cobalt Oxide for Sodium‐Ion Batteries
Authors: Yang Jianping , Zhou Tengfei , Zhu Rui , Chen Xinqi , Guo Zaiping , Fan Jianwei , Liu Hua Kun , Zhang Wei‐Xian
Published: November 2015

Highly ordered mesoporous cobalt oxide (m‐Co3O4) has been synthesized and applied as an electroactive material in sodium‐ion battery anodes. Mesoporous silica was used as the template for the generation of dual porosity cobalt oxide with spherical mesopores and porous nanochannels. The most notable feature of our dual porosity mesoporous Co3O4 is that the highly ordered structure can provide much better transport pathways than the reference bulk Co3O4 derived nanostructure, because it can facilitate the mass transport of electrolyte in the larger pores and sodium ion diffusion in the smaller pores, and also provide a large electrode–electrolyte interface for electrolyte adsorption due to the surface disorder of the Co3O4. The outstanding dual porosity mesopores in the cobalt oxide allow better transport pathways and thus lead to an initial capacity of 707 mA h g−1 at a current density of 90 mA g−1, retaining a capacity of 416 mA h g−1 after 100 cycles. The sodium uptake/extraction is confirmed to take place through a reversible conversion reaction, based on ex situ characterization techniques, which identify dual porosity mesoporous Co3O4 as a high‐performance sodium‐ion battery anode material.
Long‐Lived Foams Stabilized by a Hydrophobic Dipeptide Hydrogel
Authors: Li Tao , Nudelman Fabio , Tavacoli Joe W. , Vass Hugh , Adams Dave J. , Lips Alex , Clegg Paul S.
Published: November 2015

A hydrogel of hydrophobic dipeptides can be used to create a wet foam with long‐term stability. The dipeptide molecules self‐assemble into fiber‐like networks (due to the presence of metal ions) both at air–water interfaces and in the continuous phase. The former creates an interfacial film stabilizing the air bubbles while the latter forms a bulk gel, which prevents bubble movement and retards growth. If the storage modulus (G′) of the bulk hydrogel is sufficiently high it can stop the coarsening of the air bubbles and thus dramatically improve the stability of the foam. Cryogenic scanning electron microscopy and Raman spectra reveals the width of the fibers (200 nm) and that they are held together by hydrogen bonds. In the absence of bubbles, phase separation is observed between a hydrogel and a water‐rich phase; in the foam this can be suppressed provided that the concentration of dipeptides and metal ions are sufficiently high. It is speculated that the resistance of the bubble arrangement to compaction and hence further drainage arrests the process of phase separation. This foam system has the advantages of long stability, low cost, as well as easy preparation; therefore, it has potential applications in food manufacturing, drug delivery, and personal care industries.
Understanding Open‐Circuit Voltage Loss through the Density of States in Organic Bulk Heterojunction Solar Cells
Authors: Collins Samuel D. , Proctor Christopher M. , Ran Niva A. , Nguyen Thuc‐Quyen
Published: November 2015

The field of organic photovoltaics has recently produced highly efficient single‐junction cells with power conversion efficiency >10%, yet the open‐circuit voltage (VOC) remains relatively low in many high performing systems. An accurate picture of the density of states (DOS) in working solar cells is crucial to understanding the sources of voltage loss, but remains difficult to obtain experimentally. Here, the tail of the DOS is characterized in a number of small molecule bulk heterojunction solar cells from the charge density dependence of VOC, and is directly compared to the disorder present within donor and acceptor components as measured by Kelvin probe. Using these DOS distributions, the total energy loss relative to the charge transfer state energy (ECT)—ranging from ≈0.5 to 0.7 eV—is divided into contributions from energetic disorder and from charge recombination, and the extent to which these factors limit the VOC is assessed.
Disrupted lymphocyte homeostasis in hepatitis‐associated acquired aplastic anemia is associated with short telomeres
Authors: Babushok Daria V. , Grignon Anne‐Laure , Li Yimei , Atienza Jamie , Xie Hongbo M. , Lam Ho‐Sun , Hartung Helge , Bessler Monica , Olson Timothy S.
Published: November 2015

Hepatitis‐associated aplastic anemia (HAA) is a variant of acquired aplastic anemia (AA) in which immune‐mediated bone marrow failure (BMF) develops following an acute episode of seronegative hepatitis. Dyskeratosis congenita (DC) is an inherited BMF syndrome characterized by the presence of short telomeres, mucocutaneous abnormalities, and cancer predisposition. While both conditions may cause BMF and hepatic impairment, therapeutic approaches are distinct, making it imperative to establish the correct diagnosis. In clinical practice, lymphocyte telomere lengths (TL) are used as a first‐line screen to rule out inherited telomeropathies before initiating treatment for AA. To evaluate the reliability of TL in the HAA population, we performed a retrospective analysis of TL in 10 consecutively enrolled HAA patients compared to 19 patients with idiopathic AA (IAA). HAA patients had significantly shorter telomeres than IAA patients (P = 0.009), including four patients with TL at or below the 1st percentile for age‐matched controls. HAA patients had no clinical features of DC and did not carry disease‐causing mutations in known genes associated with inherited telomere disorders. Instead, short TLs were significantly correlated with severe lymphopenia and skewed lymphocyte subsets, features characteristic of HAA. Our results indicate the importance of caution in the interpretation of TL measurements in HAA, because, in this patient population, short telomeres have limited specificity. Am. J. Hematol. 91:243–247, 2016. © 2015 The Authors. American Journal of Hematology Published by Wiley Periodicals, Inc.
Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: 10‐Color flow cytometry diagnosis and HyperCVAD therapy
Authors: Deotare Uday , Yee Karen W.L. , Le Lisa W. , Porwit Anna , Tierens Anne , Musani Rumina , Barth David , Torlakovic Emina , Schimmer Aaron , Schuh Andre C. , Seftel Matthew , Minden Mark D. , Gupta Vikas , Hyjek Elizabeth
Published: November 2015

Few studies describe the comprehensive immunophenotypic pattern of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in the bone marrow and its treatment. This retrospective analysis evaluates the diagnostic flow cytometry (FCM) pattern and outcome of nine patients diagnosed with BPDCN. A four‐tube 10‐color FCM panel used for diagnosis of acute leukemia (AL), showed cells in the blast gate (CD45dim/low SSC) and were positive for CD4(bright), CD33(dim), CD56(heterogenous), CD123(bright), CD36, CD38, HLA‐DR, CD71. Seven patients received front‐line induction therapy with HyperCVAD with an overall response rate of 86%. Five of six responders underwent planned allogeneic hematopoietic cell transplantation (allo‐HCT). For a median follow up of 13.3 months, the 1‐year disease free survival and overall survival were 56 and 67%, respectively. An accurate diagnosis of BPDCN can be made by 10‐color FCM using a four‐tube AL panel demonstrating a characteristic pattern of antigen expression. Front‐line induction chemotherapy with HyperCVAD can yield high remission rates, but allo‐HCT is required for long‐term durable remissions. Am. J. Hematol. 91:283–286, 2016. © 2015 Wiley Periodicals, Inc.
The Voyage of Discovery of the Higgs Boson at the LHC
Authors: Virdee Tejinder S.
Published: November 2015

The journey in search for the Higgs boson started in earnest with the discovery of the W and Z bosons. The LHC accelerator, the ATLAS and CMS experiments were conceived in the late 1980s and early 1990s, and it took two decades to turn the concepts to reality. Novel and innovative technologies needed to be developed and turned into superbly functioning engines for providing proton‐proton collisions in the case of the LHC and physics results in the case of the experiments. The most significant discovery so far to emerge from the LHC project is that of a heavy scalar boson, announced on 4th July 2012. The data collected so far point strongly to its properties as those expected for the Higgs boson associated with the Brout‐Englert‐Higgs mechanism.
Conferring Phosphorogenic Properties on Iridium(III)‐Based Bioorthogonal Probes through Modification with a Nitrone Unit
Authors: Lee Lawrence Cho‐Cheung , Lau Jonathan Chun‐Wai , Liu Hua‐Wei , Lo Kenneth Kam‐Wing
Published: November 2015

The use of bioorthogonal probes that display fluorogenic or phosphorogenic properties is advantageous to the labeling and imaging of biomolecules in live cells and organisms. Herein we present the design of three iridium(III) complexes containing a nitrone moiety as novel phosphorogenic bioorthogonal probes. These probes were non‐emissive owing to isomerization of the C=N group but showed significant emission enhancement upon cycloaddition reaction with strained cyclooctynes. Interestingly, the connection of the nitrone ligand to the cationic iridium(III) center led to accelerated reaction kinetics. These nitrone complexes were also identified as phosphorogenic bioorthogonal labels and imaging reagents for cyclooctyne‐modified proteins. These findings contribute to the development of phosphorogenic bioorthogonal probes and imaging reagents.
Enhancing Energetic Properties and Sensitivity by Incorporating Amino and Nitramino Groups into a 1,2,4‐Oxadiazole Building Block
Authors: Tang Yongxing , Gao Haixiang , Mitchell Lauren A. , Parrish Damon A. , Shreeve Jean'ne M.
Published: November 2015

A single nitrogen‐rich heterocyclic ring with many energetic groups is expected to exhibit excellent detonation performance. We report an effective approach for the synthesis of 3‐amino‐5‐nitramino‐1,2,4‐oxadiazole, which has nitramino and amino groups in the same building block. The single‐crystal X‐ray structure shows layered hydrogen‐bonding pairs as well as the presence of a water molecule which ensure insensitivity. Through incorporation of a cation, the hydrazinium or hydroxylammonium salts exhibit good energetic performance and acceptable sensitivities.
Synthesis, characterization and, swelling behavior of semi‐IPN nanocomposite hydrogels of alginate with poly(N‐isopropylacrylamide) crosslinked by nanoclay
Authors: Calik Meltem Kasapoglu , Ozdemir Murat
Published: November 2015

pH and temperature responsive nanocomposite hydrogels were synthesized with sodium alginate (NaAlg), N‐isopropylacrylamide (NIPA), and nanoclay. The structure, morphology, thermal behavior, and swelling and deswelling behaviors of the hydrogels were studied. The NaAlgm/PNIPA/Clayn hydrogels revealed a highly porous structure in which the pore sizes decreased and the amount of pores increased with increasing the nanoclay content in the hydrogels. PNIPA retained its own characteristics regardless of the amount of NaAlg and nanoclay. The effect of pH and nanoclay content on the swelling and effect of temperature on the deswelling behavior were investigated. The equilibrium swelling ratios of the nanocomposite hydrogels increased with increasing the pH from 2 to 6. The maximum swelling was attained at pH 6. Deswelling increased with increasing the nanoclay content in the hydrogels. The hydrogels were found to be pH and temperature responsive. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016, 133, 43222.
Structural Modifications of Benzimidazoles via Multi‐Step Synthesis and Their Impact on Sirtuin‐Inhibitory Activity
Authors: Yoon Yeong Keng , Choon Tan Soo
Published: November 2015

Benzimidazole derivatives have been shown to possess sirtuin‐inhibitory activity. In the continuous search for potent sirtuin inhibitors, systematic changes on the terminal benzene ring were performed on previously identified benzimidazole‐based sirtuin inhibitors, to further investigate their structure–activity relationships. It was demonstrated that the sirtuin activities of these novel compounds followed the trend where meta‐substituted compounds possessed markedly weaker potency than ortho‐ and para‐substituted compounds, with the exception of halogenated substituents. Molecular docking studies were carried out to rationalize these observations. Apart from this, the methods used to synthesize the interesting compounds are also discussed.
Influences of the Pacific Decadal Oscillation on the East Asian Summer Monsoon in non‐ENSO years
Authors: Dong Xiao
Published: November 2015

The impact of different phases of the Pacific Decadal Oscillation (PDO) on East Asia summer monsoon and related precipitation in non‐ENSO (El Niño‐Southern Oscillation) years is examined in this article. Associated with the large‐scale sea surface temperature and circulation change, anomalous summer (JJA mean) precipitation in East China shows tripolar pattern, with increased (decreased) precipitation in the Yangtze‐River Valley (North and South China) in positive PDO phase without ENSO. Besides, the western Pacific subtropical high exhibits expansion and westward shift in positive PDO phase along with significantly different sub‐seasonal variation.
Depletion interactions and modulation of DNA‐intercalators binding: Opposite behavior of the “neutral” polymer poly(ethylene‐glycol)
Authors: Crisafuli F. A. P. , da Silva L. H. M. , Ferreira G. M. D. , Ramos E. B. , Rocha M. S.
Published: November 2015

In this work we have investigated the role of high molecular weight poly(ethylene‐glycol) 8000 (PEG 8000) in modulating the interactions of the DNA molecule with two hydrophobic compounds: Ethidium Bromide (EtBr) and GelRed (GR). Both compounds are DNA intercalators and are used here to mimic the behavior of more complex DNA ligands such as chemotherapeutic drugs and proteins whose domains intercalate DNA. By means of single‐molecule stretching experiments, we have been able to show that PEG 8000 strongly shifts the binding equilibrium between the intercalators and the DNA even at very low concentrations (1% in mass). Additionally, microcalorimetry experiments were performed to estimate the strength of the interaction between PEG and the DNA ligands. Our results suggest that PEG, depending on the system under study, may act as an “inert polymer” with no enthalpic contribution in some processes but, on the other hand, it may as well be an active (non‐neutral) osmolyte in the context of modulating the activity of the reactants and products involved in DNA‐ligand interactions. © 2015 Wiley Periodicals, Inc. Biopolymers 105: 227–233, 2016.
Development and validation of a new dynamic computer‐controlled model of the human stomach and small intestine
Authors: Guerra Aurélie , Denis Sylvain , le Goff Olivier , Sicardi Vincent , François Olivier , Yao Anne‐Françoise , Garrait Ghislain , Manzi Aimé Pacifique , Beyssac Eric , Alric Monique , Blanquet‐Diot Stéphanie
Published: November 2015

For ethical, regulatory, and economic reasons, in vitro human digestion models are increasingly used as an alternative to in vivo assays. This study aims to present the new Engineered Stomach and small INtestine (ESIN) model and its validation for pharmaceutical applications. This dynamic computer‐controlled system reproduces, according to in vivo data, the complex physiology of the human stomach and small intestine, including pH, transit times, chyme mixing, digestive secretions, and passive absorption of digestion products. Its innovative design allows a progressive meal intake and the differential gastric emptying of solids and liquids. The pharmaceutical behavior of two model drugs (paracetamol immediate release form and theophylline sustained release tablet) was studied in ESIN during liquid digestion. The results were compared to those found with a classical compendial method (paddle apparatus) and in human volunteers. Paracetamol and theophylline tablets showed similar absorption profiles in ESIN and in healthy subjects. For theophylline, a level A in vitro–in vivo correlation could be established between the results obtained in ESIN and in humans. Interestingly, using a pharmaceutical basket, the swelling and erosion of the theophylline sustained release form was followed during transit throughout ESIN. ESIN emerges as a relevant tool for pharmaceutical studies but once further validated may find many other applications in nutritional, toxicological, and microbiological fields. Biotechnol. Bioeng. 2016;113: 1325–1335. © 2015 Wiley Periodicals, Inc.
A conceptual framework for navigating the superficial territories of the face: Relevant anatomic points for the dermatologic surgeon
Authors: Christensen Kevin N. , Macfarlane Deborah F. , Pawlina Wojciech , King Michael , Lachman Nirusha
Published: November 2015

Recent publications in the dermatologic surgery literature have sparked a re‐emergence of interest in anatomy relevant for the Mohs surgeon necessitating a re‐visit of under‐appreciated concepts, regarding the topography of the face and its visceral contents from a surgically relevant perspective. This paper presents a pre‐operative review and a conceptual framework for intra‐operative planning for Mohs micrographic surgery and reconstruction. The key concepts presented are based on a series of (1) reviews regarding clinically significant points aimed at improving outcomes for reconstructive surgery, (2) anatomical dissections of fresh frozen cadavers, and (3) surgical experience of the authors. Basic anatomical concepts have been assimilated, surgically evaluated and re‐directed toward the dermatologic surgeon in the hope that improved anatomic competence will reduce surgical hesitance. Clin. Anat. 29:237–246, 2016. © 2015 Wiley Periodicals, Inc.
Erythropoietin‐enhanced endothelial progenitor cell recruitment in peripheral blood and renal vessels during experimental acute kidney injury in rats
Authors: Cakiroglu Figen , Enders‐Comberg Sora Maria , Pagel Horst , Rohwedel Jürgen , Lehnert Hendrik , Kramer Jan
Published: November 2015

Beneficial effects of erythropoietin (EPO) have been reported in acute kidney injury (AKI) when administered prior to induction of AKI. We studied the effects of EPO administration on renal function shortly after ischemic AKI. For this purpose, rats were subjected to renal ischemia for 30 min and EPO was administered at a concentration of 500 U/kg either i.v. as a single shot directly after ischemia or with an additional i.p. dose until 3 days after surgery. The results were compared with AKI rats without EPO application and a sham‐operated group. Renal function was assessed by measurement of serum biochemical markers, histological grading, and using an isolated perfused kidney (IPK) model. Furthermore, we performed flow cytometry to analyze the concentration of endothelial progenitor cells (EPCs) in the peripheral blood and renal vessels. Following EPO application, there was only a statistically non‐significant tendency of serum creatinine and urea to improve, particularly after daily EPO application. Renal vascular resistance and the renal perfusion rate were not significantly altered. In the histological analysis, acute tubular necrosis was only marginally ameliorated following EPO administration. In summary, we could not demonstrate a significant improvement in renal function when EPO was applied after AKI. Interestingly, however, EPO treatment resulted in a highly significant increase in CD133‐ and CD34‐positive EPC both in the peripheral blood and renal vessels.
A High‐Gradient Magnetic Separator for Highly Viscous Process Liquors in Industrial Biotechnology
Authors: Roth Hans‐Christian , Prams Andreas , Lutz Michael , Ritscher Jonathan , Raab Moritz , Berensmeier Sonja
Published: November 2015

Following the demand for highly efficient processes in biotechnology, an innovative and cost‐effective permanent magnet‐based high‐gradient magnetic separator with static magnetic filters (SMF) is presented. The laboratory‐scale prototype has a high particle capacity and is characterized by an outstanding separation performance. Low‐cost magnetic nanoparticles (MNPs, hydrodynamic diameter 100 – 200 nm) were separated from highly viscous sucrose solutions. Losses of MNPs with filtrate remained very low. The in situ implementation of ultrasound technology during MNP‐backwashing yielded excellent MNP recovery efficiencies. By applying a non‐stick coating onto the SMF surface, the MNP recovery efficiency could be enhanced significantly compared to conventional SMFs.
Silicon‐ and Tin‐Containing Open‐Chain and Eight‐Membered‐Ring Compounds as Bicentric Lewis Acids toward Anions
Authors: Wendji Anicet Siakam , Dietz Christina , Kühn Silke , Lutter Michael , Schollmeyer Dieter , Hiller Wolf , Jurkschat Klaus
Published: November 2015

Herein, we report the syntheses of silicon‐ and tin‐containing open‐chain and eight‐membered‐ring compounds Me2Si(CH2SnMe2X)2 (2, X=Me; 3, X=Cl; 4, X=F), CH2(SnMe2CH2I)2 (7), CH2(SnMe2CH2Cl)2 (8), cyclo‐Me2Sn(CH2SnMe2CH2)2SiMe2 (6), cyclo‐(Me2SnCH2)4 (9), cyclo‐Me(2−n)XnSn(CH2SiMe2CH2)2SnXnMe(2−n) (5, n=0; 10, n=1, X=Cl; 11, n=1, X=F; 12, n=2, X=Cl), and the chloride and fluoride complexes NEt4[cyclo‐ Me(Cl)Sn(CH2SiMe2CH2)2Sn(Cl)Me⋅F] (13), PPh4[cyclo‐Me(Cl)Sn(CH2SiMe2CH2)2Sn(Cl)Me⋅Cl] (14), NEt4[cyclo‐Me(F)Sn(CH2SiMe2CH2)2Sn(F)Me⋅F] (15), [NEt4]2[cyclo‐Cl2Sn(CH2SiMe2CH2)2SnCl2⋅2 Cl] (16), M[Me2Si(CH2Sn(Cl)Me2)2⋅Cl] (17 a, M=PPh4; 17 b, M=NEt4), NEt4[Me2Si(CH2Sn(Cl)Me2)2⋅F] (18), NEt4[Me2Si(CH2Sn(F)Me2)2⋅F] (19), and PPh4[Me2Si(CH2Sn(Cl)Me2)2⋅Br] (20). The compounds were characterised by electrospray mass‐spectrometric, IR and 1H, 13C, 19F, 29Si, and 119Sn NMR spectroscopic analysis, and, except for 15 and 18, single‐crystal X‐ray diffraction studies.
Asymmetric Total Synthesis of (+)‐Ryanodol and (+)‐Ryanodine
Authors: Masuda Kengo , Koshimizu Masaki , Nagatomo Masanori , Inoue Masayuki
Published: November 2015

(+)‐Ryanodine (1) is the ester derivative of 1H‐pyrrole‐2‐carboxylic acid and the complex terpenoid (+)‐ryanodol (2), which possesses eleven contiguous stereogenic centers on the ABCDE‐ring system. Compound 1 is known to be a potent modulator of intracellular calcium release channels, whereas the activity of 2 is significantly weaker. To chemically construct 1, the multiple oxygen functional groups must be installed on the fused pentacycle in stereoselective fashions and the extremely hindered C3‐hydroxy group must be acylated in a site‐selective manner. First, the total synthesis of 2 was accomplished by introducing the five stereocenters from the previously prepared enantiopure ABDE‐ring 7. Stereoselective construction of the C3‐secondary, C2‐ and C6‐tertiary alcohols was achieved by three nucleophilic reactions. The C9‐ and C10‐trisubstituted carbon centers were regio‐ and stereoselectively introduced by hydroboration/oxidation of the six‐membered C‐ring, which was formed by the ring‐closing metathesis reaction. Direct esterification of the C3‐alcohol with pyrrole‐2‐carboxylic acid proved unsuccessful; therefore, we developed a new, two‐step protocol for attachment of the pyrrole moiety. The C3‐hydroxy group was first converted into the less sterically cumbersome glycine ester, which was then transformed into the pyrrole ring through condensation with 1,3‐bis(dimethylamino)allylium tetrafluoroborate. This procedure resulted in the first total synthesis of 1.
Incremental Tuning Up of Fluorous Phenazine Acceptors
Authors: Castro Karlee P. , Clikeman Tyler T. , DeWeerd Nicholas J. , Bukovsky Eric V. , Rippy Kerry C. , Kuvychko Igor V. , Hou Gao‐Lei , Chen Yu‐Sheng , Wang Xue‐Bin , Strauss Steven H. , Boltalina Olga V.
Published: November 2015

In a simple, one‐step direct trifluoromethylation of phenazine with CF3I we prepared and characterized nine (poly)trifluoromethyl derivatives with up to six CF3 groups. The electrochemical reduction potentials and gas‐phase electron affinities show a direct, strict linear relation to the number of CF3 groups, with phenazine(CF3)6 reaching a record‐high electron affinity of 3.24 eV among perfluoroalkylated polyaromatics.
Synthesis of Three‐Dimensional Butterfly Slit‐Cyclobisazaanthracenes and Hydrazinobisanthenes through One‐Step Cyclodimerization and Their Properties
Authors: Yamamoto Koji , Higashibayashi Shuhei
Published: November 2015

New three‐dimensional (3D) π‐conjugated molecules, butterfly‐shaped slit‐cyclobisazaanthracenes, were synthesized in high yields by Ni‐mediated one‐step cyclodimerization of dibromoazaanthracenes with a dimethylacridine, phenothiazine, or acridone skeleton. The 3D slit butterfly shape was formed by folded azaanthracene skeletons. Closure of the slit via NN bond formation afforded hydrazinobisanthenes with an embedded hydrazine structure in a bisanthene skeleton, which exhibited a 3D butterfly or a 2D plane structure depending on the type of heterocycle used. Extensive study of the stereoselective chemical reactivity of the butterfly shape, X‐ray analysis, DFT calculations, electrochemical/chemical oxidations, and photophysical measurements revealed that the properties of these materials included stereoselective oxidation, a rigid or flexible butterfly shape, dynamic conformational behavior, unique crystal‐packing structures, excellent electron donation with low oxidation potential, a radical cation, a long absorption wavelength, and fluorescence property.
Bifunctional Furfuryl Cations Strategy: Three‐Component Synthesis of Enamidyl Triazoles
Authors: Yang Hengtuo , Gou Jing , Guo Jiawei , Duan Dongyu , Zhao Yu‐Ming , Yu Binxun , Gao Ziwei
Published: November 2015

A new multicomponent synthesis of functionalized enamidyl triazoles starting from simple and readily available starting materials is described. A simple treatment of a dichloromethane solution of an azide, amine, and 5‐bromo‐2‐furylcarbinol with a Lewis acid provides the enamidyl triazole in good to high yield. A triple domino sequence, formal [3+2] cycloaddition/ring‐opening/amidation, is involved in this new skeleton‐generating reaction.
Structural basis of the Inv compartment and ciliary abnormalities inInv/nphp2mutant mice
Authors: Tsuji Takuma , Matsuo Kazuhiko , Nakahari Takashi , Marunaka Yoshinori , Yokoyama Takahiko
Published: November 2015

The primary cilium is a hair like structure protruding from most mammalian cells. The basic design of the primary cilium consists of a nine microtubule doublet structure (the axoneme). The Inv compartment, a distinct proximal segment of the ciliary body, is defined as the region in which the Inv protein is localized. Inv gene is a responsible gene for human nephronophthisis type2 (NPHP2). Here, we show that renal cilia have a short proximal microtubule doublet region and a long distal microtubule singlet region. The length of the Inv compartment was similar to that of the microtubule doublet region, suggesting a possibility that the doublet region is the structural basis of the Inv compartment. Respiratory cilia ofinvmouse mutants had ciliary rootlet malformation and showed reduced ciliary beating frequency and ciliary beating angle, which may explain recurrent bronchitis in NPHP2 patients. In multiciliated tracheal cells, most Inv proteins were retained in the basal body and did not accumulate in the Inv compartment. These results suggest that the machinery to transport and retain Inv in cilia is different between renal and tracheal cilia and that Inv may function in the basal body of tracheal cells. © 2015 Wiley Periodicals, Inc.
Serpin A1 C‐Terminal Peptides as Collagen Turnover Modulators
Authors: Pascarella Simona , Tiberi Caterina , Sabatino Giuseppina , Nuti Francesca , Papini Anna Maria , Giovannelli Lisa , Rovero Paolo
Published: November 2015

The modulation of collagen turnover can be a relevant pharmacological target in the context of treating either pathological or pathophysiological conditions, such as collagen‐related diseases and skin aging. Our recent work has focused on the search for short‐chain peptides as lead compounds for further development of compounds that enhance the production of type I collagen. In this study we selected and synthesized overlapping peptides of the C‐terminal portion of serpin A1 (residues 393–418), the impact of which on collagen production has been reported previously, in order to identify shorter and still active fragments and to provide insight on the mechanisms involved. The biological activity of each fragment was evaluated with cultured normal human dermal fibroblasts, and changes in the amounts of collagen were monitored in collected culture media by a sandwich ELISA technique developed in house. Interestingly, we identified a decapeptide, termed SA1‐III (Ac‐MGKVVNPTQK‐NH2), as a promising candidate for our purposes; it is able to induce a significant increase in type I collagen levels in the culture medium of treated cells at micromolar concentrations.
Identification of Small‐Molecule Inhibitors of the Antiapoptotic Protein Myeloid Cell Leukaemia‐1 (Mcl‐1)
Authors: Beekman Andrew M. , O'Connell Maria A. , Howell Lesley A.
Published: November 2015

Protein–protein interactions (PPIs) control many cellular processes in cancer and tumour growth. Of significant interest is the role PPIs play in regulating apoptosis. The overexpression of the antiapoptosis regulating Bcl‐2 family of proteins is commonly observed in several cancers, leading to resistance towards both radiation and chemotherapies. From this family, myeloid cell leukemia‐1 (Mcl‐1) has proven the most difficult to target, and one of the leading causes of treatment resistance. Exploiting the selective PPI between the apoptosis‐regulating protein Noxa and Mcl‐1, utilising a fluorescence polarization assay, we have identified four small molecules with the ability to modulate Mcl‐1. The identified compounds were computationally modelled and docked against the Mcl‐1 binding interface to obtain structural information about their binding sites allowing for future analogue design. When examined for their activity towards pancreatic cell lines that overexpress Mcl‐1 (MiaPaCa‐2 and BxPC‐3), the identified compounds demonstrated growth inhibition, suggesting effective Mcl‐1 modulation.
Using computer‐extracted image phenotypes from tumors on breast magnetic resonance imaging to predict breast cancer pathologic stage
Authors: Burnside Elizabeth S. , Drukker Karen , Li Hui , Bonaccio Ermelinda , Zuley Margarita , Ganott Marie , Net Jose M. , Sutton Elizabeth J. , Brandt Kathleen R. , Whitman Gary J. , Conzen Suzanne D. , Lan Li , Ji Yuan , Zhu Yitan , Jaffe Carl C. , Huang Erich P. , Freymann John B. , Kirby Justin S. , Morris Elizabeth A. , Giger Maryellen L.
Published: November 2015

BACKGROUND

The objective of this study was to demonstrate that computer‐extracted image phenotypes (CEIPs) of biopsy‐proven breast cancer on magnetic resonance imaging (MRI) can accurately predict pathologic stage.

METHODS

The authors used a data set of deidentified breast MRIs organized by the National Cancer Institute in The Cancer Imaging Archive. In total, 91 biopsy‐proven breast cancers were analyzed from patients who had information available on pathologic stage (stage I, n = 22; stage II, n = 58; stage III, n = 11) and surgically verified lymph node status (negative lymph nodes, n = 46; ≥ 1 positive lymph node, n = 44; no lymph nodes examined, n = 1). Tumors were characterized according to 1) radiologist‐measured size and 2) CEIP. Then, models were built that combined 2 CEIPs to predict tumor pathologic stage and lymph node involvement, and the models were evaluated in a leave‐1‐out, cross‐validation analysis with the area under the receiver operating characteristic curve (AUC) as the value of interest.

RESULTS

Tumor size was the most powerful predictor of pathologic stage, but CEIPs that captured biologic behavior also emerged as predictive (eg, stage I and II vs stage III demonstrated an AUC of 0.83). No size measure was successful in the prediction of positive lymph nodes, but adding a CEIP that described tumor “homogeneity” significantly improved discrimination (AUC = 0.62; P = .003) compared with chance.

CONCLUSIONS

The current results indicate that MRI phenotypes have promise for predicting breast cancer pathologic stage and lymph node status. Cancer 2016;122:748–757. © 2015 American Cancer Society.
Cytologic categorization of pancreatic neoplastic mucinous cysts with an assessment of the risk of malignancy: A retrospective study based on the Papanicolaou Society of Cytopathology guidelines
Authors: Smith Amber L. , Abdul‐Karim Fadi W. , Goyal Abha
Published: November 2015

BACKGROUND

Cytology plays a pivotal role in the preoperative diagnosis of pancreatic cysts. Here the Papanicolaou Society of Cytopathology (Pap Society) guidelines were used to reclassify and assess the malignancy risk of cytology diagnoses of histologically proven pancreatic neoplastic mucinous cysts.

METHODS

A database search (January 2000 to June 2014) was performed for pancreatic neoplastic mucinous cyst resections with endoscopic ultrasound–guided fine‐needle aspiration within the preceding year. Histologic diagnoses were reclassified according to the 2010 Word Health Organization criteria. For atypical/suspicious/positive cytology diagnoses, the cytology slides were reviewed, blinded to the histologic diagnoses. The cysts were reclassified according to the Pap Society guidelines, and the findings were correlated with the histology.

RESULTS

One hundred thirty‐eight cases of pancreatic neoplastic mucinous cysts were retrieved. Eleven cases with atypical/suspicious cytology diagnoses with unavailable slides were excluded. The remaining 127 cases included 81 intraductal papillary mucinous neoplasms and 46 mucinous cystic neoplasms. The sensitivity of cytology for the diagnosis of neoplastic mucinous cysts was 76.4%. The sensitivity, specificity, and accuracy of cytology for the diagnosis of malignancy (high‐grade dysplasia or worse) were 48.3%, 94.9%, and 84.3%, respectively. The risk of malignancy was 17.4% for the nondiagnostic category, 0% for the negative category, 13% for the neoplastic category, 63.6% for the atypical category, 80% for the suspicious category, and 100% for a positive diagnosis.

CONCLUSIONS

This study reveals that the Pap Society guidelines allow the accurate categorization of pancreatic neoplastic mucinous cysts with cytology. The diagnostic categories (from negative to positive) are associated with an increasing risk of malignancy, and this can further aid in patient management and risk stratification. Cancer Cytopathol 2016;124:285–93. © 2015 American Cancer Society.
Selective Killing of Breast Cancer Cells by Doxorubicin‐Loaded Fluorescent Gold Nanoclusters: Confocal Microscopy and FRET
Authors: Chattoraj Shyamtanu , Amin Asif , Jana Batakrishna , Mohapatra Saswat , Ghosh Surajit , Bhattacharyya Kankan
Published: November 2015

Fluorescent gold nanoclusters (AuNCs) capped with lysozymes are used to deliver the anticancer drug doxorubicin to cancer and noncancer cells. Doxorubicin‐loaded AuNCs cause the highly selective and efficient killing (90 %) of breast cancer cells (MCF7) (IC50=155 nm). In contrast, the killing of the noncancer breast cells (MCF10A) by doxorubicin‐loaded AuNCs is only 40 % (IC50=4500 nm). By using a confocal microscope, the fluorescence spectrum and decay of the AuNCs were recorded inside the cell. The fluorescence maxima (at ≈490–515 nm) and lifetime (≈2 ns), of the AuNCs inside the cells correspond to Au10–13. The intracellular release of doxorubicin from AuNCs is monitored by Förster resonance energy transfer (FRET) imaging.
Assessing free lattice and structure parameters from the atomic level
Authors: Paufler Peter
Published: November 2015

Data mining of lattice and structure parameters with the aid of the Inorganic Crystal Structure Database revealed a correlation between the abundance of parameter values observed and geometric features of interatomic distances. Working out this finding enabled distinguished lattice and structure parameters to be attributed to special bonds. The method is illustrated dealing with two examples of a hexagonal and a cubic structure type.
Catalytic Activity and Impedance Behavior of Screen‐Printed Nickel Oxide as Efficient Water Oxidation Catalysts
Authors: Singh Archana , Fekete Monika , Gengenbach Thomas , Simonov Alexandr N. , Hocking Rosalie K. , Chang Shery L. Y. , Rothmann Mathias , Powar Satvasheel , Fu Dongchuan , Hu Zheng , Wu Qiang , Cheng Yi‐Bing , Bach Udo , Spiccia Leone
Published: November 2015

We report that films screen printed from nickel oxide (NiO) nanoparticles and microballs are efficient electrocatalysts for water oxidation under near‐neutral and alkaline conditions. Investigations of the composition and structure of the screen‐printed films by X‐ray diffraction, X‐ray absorption spectroscopy, and scanning electron microscopy confirmed that the material was present as the cubic NiO phase. Comparison of the catalytic activity of the microball films to that of films fabricated by using NiO nanoparticles, under similar experimental conditions, revealed that the microball films outperform nanoparticle films of similar thickness owing to a more porous structure and higher surface area. A thinner, less‐resistive NiO nanoparticle film, however, was found to have higher activity per Ni atom. Anodization in borate buffer significantly improved the activity of all three films. X‐ray photoelectron spectroscopy showed that during anodization, a mixed nickel oxyhydroxide phase formed on the surface of all films, which could account for the improved activity. Impedance spectroscopy revealed that surface traps contribute significantly to the resistance of the NiO films. On anodization, the trap state resistance of all films was reduced, which led to significant improvements in activity. In 1.00 m NaOH, both the microball and nanoparticle films exhibit high long‐term stability and produce a stable current density of approximately 30 mA cm−2 at 600 mV overpotential.
It is time to beelieve the CD1a hype!
Authors: Krovi Sai Harsha , Gapin Laurent
Published: November 2015

Conventional T cells have historically been linked to exacerbating allergy. By efficiently generating primarily TH2 cells, allergens skew the immune response to produce IL‐4, IL‐13, and IgE. Previously, CD1a‐responsive T cells were shown to functionally respond to bee and wasp venom allergens. In this issue of the European Journal of Immunology, Subramaniam et al. [Eur. J. Immunol. 2016. 46: 242–252] show that more functionally active CD1a‐restricted cells are present in bee venom‐allergic patients than in healthy patients. Additionally, the authors show that these cells are not as frequently found in individuals receiving venom immunotherapy. Consequently, this study implicates CD1a‐reactive cells as the primary responders to venom allergy, which considerably regulate the downstream immune response.
Formation of Mono‐, Di‐ and Trinuclear Species in the Self‐Assembly of Bis(pyraz­olyl)(pyridin‐3‐yl)methane Ligands and ­Metals with Different Coordination Geometries
Authors: Durá Gema , Carrión M. Carmen , Jalón Félix A. , Manzano Blanca R. , Rodríguez Ana M.
Published: November 2015

The self‐assembly of ligands bis(pyrazol‐1‐yl)(pyridin‐3‐yl)methane (bpzm3py, L1) and bis(3,5‐dimethylpyrazol‐1‐yl)(pyridin‐3‐yl)methane (bpz*m3py, L2), with metals of different geometries has been investigated. The use of [PdCl2(PhCN)2] led to the formation of trinuclear species of the type [PdCl2(μ‐L)PdCl2(μ‐L)PdCl2] with two types of palladium centre. The use of Ni(NO3)2 led to the formation of cyclic dimers [Ni(μ‐L)(NO3)2]2, in which the ligands L adopt a head‐to‐tail disposition, whereas the reaction with CoCl2 led to mononuclear species [CoCl2(L)] with an uncoordinated pyridine ring. The reaction with silver salts gave, in all cases, cyclic dimers with tetracoordinate metal ions. In the cases of AgClO4 and AgCF3SO3, the products were [Ag(μ‐L)(X)]2 with the anions coordinated to the metal ions. In the case of AgBF4, the anion remained uncoordinated and the resulting species, [Ag(μ‐L)(S)2]2(BF4)2, contained coordinated crystallisation solvents (S = MeOH, acetone). The asymmetry in the ligands created by the 3‐substituent in the pyridine ring led to the generation of chirality in the case of the nickel and silver cyclic dimers. The supramolecular structures were analysed and a comparison was made with the structures of complexes that contain the related ligands bis(pyrazol‐1‐yl)(pyridin‐4‐yl)methane and bis(3,5‐dimethylpyrazol‐1‐yl)(pyridin‐4‐yl)methane. A “pyrazolyl embrace” was observed in a silver complex with the non‐methylated ligand L1.
Functional Molecules for Grafting onto Ionic Surfaces
Authors: Pujol Adeline R. , Bataillé Sonia , Gourdon André
Published: November 2015

The 2D adsorption of molecules onto insulating surfaces is of increasing interest for future devices in emerging technologies such as molecular electronics, sensors, single‐molecule optics, and on‐surface synthesis. However, most attempts to stabilize molecular structures on these substrates have been hampered by weak molecule–surface interactions and so there is a need to develop organic molecules bearing suitable grafting groups. We report herein the synthesis of a series of molecules designed to be physisorbed onto alkali halide crystalline surfaces. They comprise a rigid central benzene or triphenylene core bearing, respectively, two or six alkyl ether chains terminated by cyano, carboxylic, α‐amino acids, or 1,2,3‐triazoles as anchoring groups.
Commentary: Challenging Views and Creative Insights from a Social Cultural Perspective
Authors: Hui Anna N. N.
Published: November 2015

This commentary focuses on the challenging views and creative insights inspired by the four articles in this special issue of the journal. The studies have integrated creativity research with social psychological and cultural perspectives. I have highlighted the unique contribution of how Karwowski, Tanggaard, Glăveanu, and Hennessey have each advanced theory formation with empirical evidence indicating strong convergent and concurrent validity.
Commentary: Toward Convergence in Creativity Inquiry
Authors: Tan Ai‐Girl , Wong Meng‐Ee
Published: November 2015

This commentary is about reflection in the new language of creativity and the meanings of inquiry into creative life. The authors of the commentary adopt the cultural paradigm of psychology of creativity. They praise effortful creativity of the authors who submitted the articles to this special issue. Their studies employed diverse methods of inquiry into how creativity unfolds in flourishing environments. The authors of this commentary share their experiences in nurturing creativity in the context of educating people with special needs. They conclude preliminary that inclusive education shall focus on resolving incongruence in cultural development and on accepting different creativity developmental styles.
Effect of Immobilized Thiolated Glycosaminoglycans on Fibronectin Adsorption and Behavior of Fibroblasts
Authors: Köwitsch Alexander , Niepel Marcus S. , Michanetzis Georgios P. A. , Missirlis Yannis F. , Groth Thomas
Published: November 2015

Glycosaminoglycans (GAGs) chondroitin sulfate, heparin, hyaluronan, and sulfated hyaluronan are lower and higher thiolated to enable a one‑step covalent modification of gold or vinyl‑terminated surfaces. Measurements of water contact angle and zeta potentials reveal that sulfated GAG‑modified surfaces are more wettable and possess a negative surface potential. Additionally, higher thiolated GAGs (tGAGs) exhibit increased wettability and higher surface roughness. Fibronectin (FN) adsorption increases with sulfation degree of tGAGs. The tGAG‑functionalized surfaces with higher degree of sulfation promote fibroblast adhesion most under serum‐free conditions. The preadsorption of FN allows for more cell adhesion on tGAG surfaces. Metabolic activity measurements show that cell growth is enhanced for tGAGs up to a certain thiolation degree. Overall, thiolation of GAGs does not hamper their bioactivity toward proteins and cells, which make them highly interesting for biomimetic surface modification of implants and tissue engineering scaffolds.
Graphene Oxide–Poly(ethylene glycol) methyl ether methacrylate Nanocomposite Hydrogels
Authors: Mangadlao Joey Dacula , Huang Rongzhi , Foster Edward Lee , Pangilinan Katrina D. , Danda Chaitanya , Advincula Abigail , Maia João M. , Advincula Rigoberto C.
Published: November 2015

In this paper, covalently linked graphene oxide–poly(ethylene glycol) methyl ether methacrylate–reversible addition‐fragmentation chain transfer (GO–PEGMEMA–RAFT) and physically mixed GO–PEGMEMA hydrogel nanocomposites are synthesized. Spectroscopic and imaging techniques such as UV–vis, Fourier transform infrared, Raman spectroscopy, and transmission electron microscopy show that the PEGMEMA is successfully grafted on GO sheets. The rheology of the nanocomposites is studied by small angle oscillatory shear, which shows a competition between reinforcement and lubrication behavior of GO. In the case where lubrication effect dominates reinforcement, the covalently linked GO–PEGMEMA–RAFT has higher G′ compared to the physically mixed GO‐PEGMEMA. Hence, in the covalently linked system, the grafted polymer chains appear to minimize the lubrication effect.

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Spermatozoa in the Peak District
Authors: Wolfner Mariana F. , Montgomerie Robert
Published: November 2015

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Mol. Reprod. Dev. 83: 8–11, 2016. © 2015 Wiley Periodicals, Inc.
Increased collagen cross‐linking is a signature of dystrophin‐deficient muscle
Authors: Smith Lucas R. , Hammers David W. , Sweeney H. Lee , Barton Elisabeth R.
Published: November 2015

Introduction

Collagen cross‐linking is a key parameter in extracellular matrix (ECM) maturation, turnover, and stiffness. We examined aspects of collagen cross‐linking in dystrophin‐deficient murine, canine, and human skeletal muscle.

Methods

DMD patient biopsies and samples from mdx mice and golden retriever muscular dystrophy dog samples (with appropriate controls) were analyzed. Collagen cross‐linking was evaluated using solubility and hydroxyproline assays. Expression of the cross‐linking enzyme lysyl oxidase (LOX) was determined by real‐time polymerase chain reaction, immunoblotting, and immunofluorescence.

Results

LOX protein levels are increased in dystrophic muscle from all species evaluated. Dystrophic mice and dogs had significantly higher cross‐linked collagen than controls, especially in the diaphragm. Distribution of intramuscular LOX was heterogeneous in all samples, but it increased in frequency and intensity in dystrophic muscle.

Conclusion

These findings implicate elevated collagen cross‐linking as an important component of the disrupted ECM in dystrophic muscles, and heightened cross‐linking is evident in mouse, dog, and man. Muscle Nerve 54: 71–78, 2016