bluuebunny/crossref_metadata_2025 huggingface dataset:
Lead Evaluation of Tetrahydroquinolines as Nonsteroidal Selective Androgen Receptor Modulators for the Treatment of Osteoporosis
Authors: Nagata Naoya , Furuya Kazuyuki , Oguro Nao , Nishiyama Daisuke , Kawai Kentaro , Yamamoto Noriko , Ohyabu Yuki , Satsukawa Masahiro , Miyakawa Motonori
Published: November 2013

Tetrahydroquinoline (THQ) was deemed to be a suitable scaffold for our nonsteroidal selective androgen receptor modulator (SARM) concept. We adapted the strategy of switching the antagonist function of cyano‐group‐containing THQ (CN‐THQ) to the agonist function and optimized CN‐THQ as an orally available drug candidate with suitable pharmacological and ADME profiles. Based on binding mode analyses and synthetic accessibility, we designed and synthesized a compound that possesses a para‐substituted aromatic ring attached through an amide linker. The long‐tail THQ derivative 6‐acetamido‐N‐(2‐(8‐cyano‐3a,4,5,9b‐tetrahydro‐3H‐cyclopenta[c]quinolin‐4‐yl)‐2‐methylpropyl)nicotinamide (1 d), which bears a para‐acetamide‐substituted aromatic group, showed an appropriate in vitro biological profile, as expected. We considered that the large conformational change at Trp741 of the androgen receptor (AR) and the hydrogen bond between 1 d and helix 12 of the AR could maintain the structure of the AR in its agonist form; indeed, 1 d displays strong AR agonistic activity. Furthermore, 1 d showed an appropriate in vivo profile for use as an orally available SARM, displaying clear tissue selectivity, with a separation between its desirable osteoanabolic effect on femoral bone mineral density and its undesirable virilizing effects on the uterus and clitoral gland in a female osteoporosis model.
Palladium Supported on Magnetic Core–Shell Nanoparticles: An Efficient and Reusable Catalyst for the Oxidation of Alcohols into Aldehydes and Ketones by Molecular Oxygen
Authors: Zhang Lei , Li Pinhua , Yang Jin , Wang Min , Wang Lei
Published: November 2013

In continuing our efforts to develop economical and ecofriendly synthetic protocols, we present a proline–palladium catalyst supported on magnetic nanoparticles (0.5 mol %) for oxidation by molecular oxygen. The supported Pd catalyst shows high activity in the oxidation of alcohols into the corresponding carbonyl compounds where easy catalyst recovery and excellent recycling efficiency are observed. It is possible to recover and reuse the grafted palladium catalysts at least eight times without significant loss of its catalytic activity.
Infrared power generation in an insulated compartment
Authors: Schwab Yosyp , Mann Harkirat S. , Lang Brian N. , Lancaster Jarrett L. , Parise Ronald J. , Vincent‐Johnson Anita J. , Scarel Giovanna
Published: November 2013

The mechanism that activates a bi‐junction power generator under the effects of heat is the Seebeck effect, that is, the production of voltage difference ΔV(t) is directly proportional to the temperature difference ΔT(t) between the “hot” and “cold” junctions of the device. This phenomenon is well established and is known as thermoelectric power generation. Here, it is shown that, instead, the causal and linear relationship between ΔV(t) and ΔT(t) is lost when continuous broadband infrared (CB‐IR) radiation illuminates a bi‐junction power generator in an insulated compartment. The observed phenomenon is IR power generation. Heat transfer calculations fail in explaining the experimental trends. The interaction between CB‐IR radiation and the charge carriers in the bi‐junction power generator might play a role in the ΔV(t) production, depending upon the geometry of the experimental setup. The longitudinal propagation of collective oscillations, for example, polaritons, in the plates protecting the “hot” and “cold” junctions of the bi‐junction power generator could explain the ΔV(t) production and the characteristic time constants. The findings should be considered in the design, fabrication, and improvement of thermopiles, power meters, and IR energy‐harvesting devices. © 2013 Wiley Periodicals, Inc. Complexity 19: 44–55, 2014
Distributed method for cracking WPA/WPA2‐PSK on multi‐core CPU and GPU architecture
Authors: Yong‐lei Liu , Zhi‐gang Jin
Published: November 2013

To overcome the limitations of the existing brute force cracking method of Wi‐Fi Protected Access/Wi‐Fi Protected Access II (WPA/WPA2)‐pre‐shared key (PSK) based on single core CPU or one core of a multi‐core CPU, a new distributed multi‐core CPU and GPU parallel cracking method (DMCG) was first proposed. Colored Petri nets was used to validate the four‐way handshake protocol and proved that DMCG could successfully crack WPA/WPA2‐PSK. In DMCG, the PSK list was distributed to each PC reasonably using distributed technology. Multiple computing cores were made up of multi‐core CPU and GPU on single PC to crack in parallel. GPU contributed to the cracking speed improvement due to the strong computing power for intensive parallel tasks. Experimental results showed that DMCG improved the cracking speed by two orders of magnitude and would exhibit more notable advantages with high‐performance distributed system as the cracking speed improved by three or four orders of magnitude, compared with the computing power of one CPU core. An improved Amdahl's law was first proposed, by which the upper bound of the cracking speedup was analyzed. Aiming to the DMCG expansion of cloud computing based on GPU, a lightweight framework called Dandelion computing model was first proposed. Moreover, the analysis of the influences of the graphics card parameters on the cracking speed was processed, and accordingly, the decision support for choosing graphics card in DMCG based on analytic hierarchy process was provided. Finally, the performance optimization of DMCG was processed. Copyright © 2013 John Wiley & Sons, Ltd.
Three‐dimensional cell groups with disordered nuclei and cellular discohesion (3DDD) are associated with high sensitivity and specificity for cystoscopic urine cytopathological diagnosis of low‐grade urothelial neoplasia
Authors: Mai Kien T , Ball Christopher G. , Kos Zuzana , Belanger Eric C , Islam Shahidul , Sekhon Harman
Published: November 2013

Cystoscopic urine obtained before the resection of low‐grade urothelial carcinoma (LGUC), with adequate cytological sampling of the tumor, frequently revealed the presence of three‐dimensional cell groups with disordered nuclei and cellular discohesion (3DDD). 936 cystoscopic urine specimens were categorized into five groups: Group 1 (80 specimens) with biopsy‐proven LGUC within 6 months of cytologic examination, Group 2 (23 specimens) with biopsy proven LGUC within 6 to 36 months of cytologic examination, Group 3 (527 specimens) with a history of LGUC but no tumor for a period of greater than 3 years, Group 4 (300 specimens) with no association with LGUC, and Group 5 (6 specimens) with urinary lithiasis. Specimens with scant cellularity accounted for 20% of those in Group 1. For 3DDD in detecting LGUC in adequate cystoscopic urine, the sensitivity was 70%, specificity was 94%. Two‐ or three‐dimensional cell groups with ordered nuclei and/or cellular non‐discohesion were often seen in specimens from Groups 4 or 5. The 3DDD was present in a significant number of cases with concurrent negative cystoscopic findings but also positive LGUC in ensuing follow‐up. In these cases, 3DDD with or without tumor identified at concurrent cystoscopy were found to be morphologically similar. Furthermore, the presence of 3DDD in 8% of Group 3 likely represents urothelial dysplasia that is not cystoscopically detectable. The high specificity and sensitivity of 3DDD is demonstrated. These findings are consistent with the decreased cell adhesion and disordered nuclear arrangement of low grade urothelial neoplasia. Diagn. Cytopathol. 2014;42:555–563. © 2013 Wiley Periodicals, Inc.
Myosin Va associates with mRNA in ribonucleoprotein particles present in myelinated peripheral axons and in the central nervous system
Authors: Calliari Aldo , Farías Joaquina , Puppo Agostina , Canclini Lucía , Mercer John A. , Munroe David , Sotelo José R. , Sotelo‐Silveira José R.
Published: November 2013

Sorting of specific mRNAs to particular cellular locations and regulation of their translation is an essential mechanism underlying cell polarization. The transport of RNAs by kinesins and dyneins has been clearly established in several cell models, including neurons in culture. A similar role appears to exist in higher eukaryotes for the myosins. Myosin Va (Myo5a) has been described as a component of ribonucleoprotein particles (RNPs) in the adult rat nervous system and associated to ZBP1 and ribosomes in ribosomal periaxoplasmic plaques (PARPs), making it a likely candidate for mediating some aspects of RNA transport in neurons. To test this hypothesis, we have characterized RNPs containing Myo5a in adult brains of rats and mice. Microarray analysis of RNAs co‐immunoprecipitated with Myo5a indicates that this motor may associate with a specific subpopulation of neuronal mRNAs. We found mRNAs encoding α‐synuclein and several proteins with functions in translation in these RNPs. Immunofluorescence analyses of RNPs showed apparent co‐localization of Myo5a with ribosomes, mRNA and RNA‐binding proteins in discrete structures present both in axons of neurons in culture and in myelinated fibers of medullary roots. Our data suggest that PARPs include RNPs bearing the mRNA coding for Myo5a and are equipped with kinesin and Myo5a molecular motors. In conclusion, we suggest that Myo5a is involved in mRNA trafficking both in the central and peripheral nervous systems. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 74: 382–396, 2014
Small leucine‐rich proteoglycans exhibit unique spatiotemporal expression profiles during cardiac valve development
Authors: Dupuis Loren E. , Kern Christine B.
Published: November 2013

Background: Small Leucine Rich Proteoglycans (SLRPs) play a role in collagen fiber formation and also function as signaling molecules. Given the importance of collagen synthesis to the cardiovascular extracellular matrix (ECM), we examined the spatiotemporal expression of SLRPs, not previously investigated in the murine heart. Results: Cardiac expression using antibodies specific for biglycan (BGN), decorin (DCN), fibromodulin (FMOD), and lumican (LUM) revealed distinct patterns among the SLRPs in mesenchymal‐derived tissues. DCN showed the most intense localization within the developing valve cusps, while LUM was evident primarily in the hinge region of postnatal cardiac valves. BGN, DCN, and FMOD were immunolocalized to regions where cardiac valves anchor into adjacent tissues. Medial (BGN) and adventitial (BGN, DCN, FMOD and LUM) layers of the pulmonary and aortic arteries also showed intense staining of SLRPs but this spatiotemporal expression varied with developmental age. Conclusions: The unique expression patterns of SLRPs suggest they have adapted to specialized roles in the cardiovascular ECM. SLRP expression patterns overlap with areas where TGFβ signaling is critical to the developing heart. Therefore, we speculate that SLRPs may not only be required to facilitate collagen fiber formation but may also regulate TGFβ signaling in the murine heart. Developmental Dynamics 243:601–611, 2014. © 2013 Wiley Periodicals, Inc.
Assessment of fat taste in individuals with and without anorexia nervosa
Authors: Schebendach Janet E. , Klein Diane A. , Mayer Laurel E.S. , Devlin Michael J. , Attia Evelyn , Walsh B. Timothy
Published: November 2013

Objective

Avoidance of dietary fat is a highly characteristic eating behavior of individuals with anorexia nervosa (AN). To date, no study has determined whether these individuals are better able to perceive the fat content of foods than individuals without AN. The goal of this study was to compare blinded taste ratings of fat‐free, low fat, and regular cream cheese in patients with AN and in normal controls (NC).

Method

AN (n = 25) and control (NC; n = 25) participants were presented with a series of nine cream cheese samples of three differing fat contents and asked to taste and rate each sample from very low to very high fat.

Results

Repeated measures ANOVA found no significant main effect of fat content and no interaction between fat content and diagnosis; however, a significant three‐way interaction between fat content, diagnosis, and trial was observed. Post hoc analysis revealed a significant fat content by trial interaction within the AN group, suggesting a significant trial effect for the fat‐free samples only with improving ability to detect fat‐free samples over repeated trials.

Discussion

The current study suggests that individuals with AN do not have a markedly greater ability to taste fat than NC, and that; therefore, fat avoidance is likely primarily based on cognitive factors. © 2013 Wiley Periodicals, Inc. (Int J Eat Disord 2014; 47:215–218)
Salivary gland resident APCs are Flt3L‐ and CCR2‐independent macrophage‐like cells incapable of cross‐presentation
Authors: Thom Jenny T. , Walton Senta M. , Torti Nicole , Oxenius Annette
Published: November 2013

Cytomegaloviruses (CMVs) disseminate within the human population via mucosal excretions, for example, from the salivary glands (SGs), which represent a privileged site of viral immune evasion and persistence. The murine CMV (MCMV) model has served to identify factors that maintain a unique virus–host relationship in this organ. In contrast to all other organs, the SG is resistant to CD8+ T‐cell mediated control of MCMV replication due to virally induced MHC class I downregulation, which is exceptionally efficient in acinar glandular epithelial cells. Uniquely to the SG, IFN‐γ producing CD4+ T cells are required for virus control. While T‐cell responses have been extensively characterized in the SG, the ontogeny and function of APCs in this organ remain to be assessed. Here, we show that macrophage‐like cells constitute the population of SG‐resident APCs in steady state and during MCMV‐induced inflammation in mice. Inflammatory monocytes, monocyte‐derived DCs as well as conventional, Flt3L‐dependent DCs do not contribute to this population. Despite supporting contact formation to CD4+ and CD8+ T cells in principle, SG‐resident APCs fail to activate the latter due to their inability to cross‐present MCMV‐derived antigen.
Quaterphenylterpyridine: Synthesis and Metal‐Ion Complexation
Authors: Lee Young Hoon , Fuyuhiro Akira , Harrowfield Jack M. , Kim Yang , Sobolev Alexandre N. , Hayami Shinya
Published: November 2013

A quaterphenylterpyridine ligand (qptpy) with the rodlike quaterphenyl unit attached in the 4′‐position has been synthesised by a Pd‐catalysed Suzuki cross‐coupling reaction. A crystal structure determination on the complex [Zn(qptpy)Cl2]·dmf (dmf = dimethylformamide) has shown the ligand to be bound in the expected N3‐tridentate manner to the essentially trigonal‐bipyramidal dichloro metal ion, with the quaterphenyl substituents involving a twisted array of the separate phenyl groups and the shortest contacts between aromatic groups involving just the polar terpyridine head groups to give an infinite, offset face‐to‐face (OFF) π‐stacking array. A comparison is made with the structures of the bis(ligand) complexes of Zn(ClO4)2 and Cd(ClO4)2 with the bromobiphenylterpyridine ligand (Brbptpy) synthesised as an intermediate for the formation of qptpy. A study of the absorption and emission spectra of qptpy and a range of its metal‐ion complexes has shown that the ligand provides a ratiometric fluorescence response for both ZnII and CdII.
Bi38 Oxocarboxylate Cages are Keplerates – Synthesis and Structural Characterization of Two Bi38 Oxocarboxylate Cages
Authors: Chandrasekhar Vadapalli , Metre Ramesh K. , Sahoo Dipankar
Published: November 2013

The reaction of 3,5‐dinitrobenzenecarboxylic acid with triphenylbismuth in a 1:1 stoichiometric ratio in toluene under reflux afforded two new Bi38 oxocarboxylate cages [Bi38(μ3‐O)22(μ4‐O)22(μ6‐O){3,5‐(NO2)2C6H3COO}20(OH)4(DMSO)16]·4DMSO·11H2O (1, DMSO = dimethyl sulfoxide) and [Bi38(μ3‐O)22(μ4‐O)22(μ6‐O){3,5‐(NO2)2C6H3COO}20(CH3COO)2(OH)2(DMF)10]·15DMF·20H2O (2, DMF = N,N‐dimethylformamide), which were obtained under different crystallization conditions. Compounds 1 and 2 are built from the coordination action of carboxylato, hydroxido, and oxido ligands and neutral solvent molecules. A detailed structural analysis of 1 reveals that the center of the core contains a {Bi6} octahedron, a Platonic polyhedron, which is encapsulated by another Platonic solid, viz., a {Bi8} cube. This entire assembly is further encapsulated by a truncated octahedral {Bi24} cage; the latter is an Archimedean solid. This structural arrangement of 1 classifies it along with Bi38 oxo cages as Keplerates, a structural family to which very few main‐group‐element‐containing compounds belong.
Disulfates from Low Temperature Synthesis in Ionic Liquids: (C5H6N)3Sm(S2O7)3 and (C5H6N)Bi(S2O7)2
Authors: Weiz Alexander , Bruns Jörn , Wickleder Mathias S.
Published: November 2013

The reactions of Bi(NO3)3·5H2O or Sm(NO3)3·6H2O with oleum (65 % SO3 in conc. H2SO4) and the pyridine (Py) complex Py·SO3 in the ionic liquid 1‐butyl‐3‐methylimidazolium hydrogen sulfate, [bmim][HSO4], yielded single crystals of (C5H6N)Bi(S2O7)2 and (C5H6N)3Sm(S2O7)3, respectively. In (C5H6N)3Sm(S2O7)3 the Sm3+ cations are ninefold coordinated by oxygen atoms in the form of a tricapped trigonal prism. The oxygen atoms belong to six chelating and six monodentate disulfate units. The anions connect the Sm3+ ions to chains according to 1∞[Sm(S2O7)6/2]3– along the crystallographic c‐axis. In (C5H6N)Bi(S2O7)2 the two crystallographic independent Bi3+ cations are in a distorted square‐prismatic oxygen coordination of eight oxygen atoms belonging to four chelating disulfate units. The connection of the Bi3+ ions leads to a corrugate layer according to 2∞[Bi(S2O7)4/2]–. In both compounds charge compensation is achieved by pyridinium cations (C5H6N)+, which are tilted towards each other and packed in a layered arrangement between the anionic units. Thermoanalytical investigations reveal the sesquioxide Sm2O3 as a residual product for the decomposition of (C5H6N)3Sm(S2O7)3.
Facile Solution‐Phase Synthesis of CuInSe2 Nanocrystals with Controlled Morphologies
Authors: Bai Tianyu , Li Feifei , Huang He , Wang Zhaorui , Shi Zhan , Li Chunguang , Wang Ge , Feng Shouhua
Published: November 2013

The morphology of CuInSe2 nanocrystals plays a key role in their functional properties. Achieving controllable morphology is significant for studying their structures and novel properties. Here, CuInSe2 nanocrystals with a trigonal‐pyramidal shape have successfully been synthesized by a facile solution‐phase method. The nanocrystals were characterized by X‐ray diffraction (XRD), transmission electron microscopy (TEM), and X‐ray photoelectron spectroscopy (XPS), etc. The morphological evolution of the CuInSe2 nanocrystals was illustrated by tuning the injection temperature of oleylamine‐selenium (OAm‐Se). In addition, CuInSe2 nanocrystals with spherical and ellipsoidal shapes were also obtained when copper stearate was used as the copper precursor.
Effect of Ligand Polarization on Asymmetric Structural Formation for Strongly Luminescent Lanthanide Complexes
Authors: Hasegawa Yasuchika , Ohkubo Tomoki , Nakanishi Takayuki , Kobayashi Atsushi , Kato Masako , Seki Tomohiro , Ito Hajime , Fushimi Koji
Published: November 2013

The effect of ligand polarization on the formation of strongly luminescent lanthanide complexes with asymmetric structures is described for the first time. The lanthanide complexes are composed of EuIII ions, three hexafluoroacetylacetonate (hfa) ligands, and two monodentate phosphine oxide ligands, namely, triphenylphosphine oxide (TPPO), p‐tolyldiphenylphosphine oxide (TPPO‐Me), tri‐p‐tolylphosphine oxide (TPPO‐3Me) or o‐phenoxyphenyldiphenylphosphine oxide (TPPO‐OPh). The luminescence properties of the EuIII complexes are characterized by their emission quantum yields, emission lifetimes, and their radiative (kr) and nonradiative (knr) rate constants. The EuIII complex with TPPO‐OPh ligands offers a markedly high emission quantum yield (72 % in [D6]acetone, 85 % in the solid state) owing to enhancement of the electric dipole transition and suppression of vibrational relaxation, which are directly related to kr and knr. The coordination geometries of the EuIII complexes are categorized by shape‐measure calculations. The EuIII complexes exhibit characteristic square‐antiprismatic or trigonal‐dodecahedral structures, depending on the ligand polarization. Strongly luminescent Eu(hfa)3(TPPO‐OPh)2 has an asymmetric dodecahedron structure. The formation of distorted dodecahedral structures with low vibrational frequencies for the enhancement of luminescence is elucidated in terms of the ligand polarization of the monodentate phosphine oxide ligands in the EuIII complexes.
Linear, Edge‐Sharing Heterometallic Trinuclear [CoII–LnIII–CoII] (LnIII = GdIII, DyIII, TbIII, and HoIII) Complexes: Slow Relaxation of Magnetization in the DyIII Derivative
Authors: Chandrasekhar Vadapalli , Das Sourav , Dey Atanu , Hossain Sakiat , Kundu Subrata , Colacio Enrique
Published: November 2013

The sequential reaction of a multisite coordination ligand (LH4) with lanthanide (III) nitrates followed by the addition of Co(NO3)2·6H2O in a 4:1:2 ratio in the presence of triethylamine afforded a series of heterometallic, linear trinuclear complexes [Co2Ln(LH3)4]·3NO3 [Ln = DyIII (1), GdIII (2), TbIII (3), and HoIII (4)]. These tricationic complexes contain nitrate counteranions. The cationic portion of these complexes consists of three metal ions that are arranged in a linear fashion; a central LnIII is present between the two terminal CoII ions and is attached to the latter through two phenoxide bridging groups. This arrangement generates two contiguous four‐membered CoLnO2 rings. The CoII ions are six‐coordinate (2N, 4O) in a distorted octahedral geometry, whereas the central lanthanide ion is eight‐coordinate (8O) in a distorted square‐antiprismatic geometry. Magnetic studies of these complexes have been performed and indicate a slow relaxation of the magnetization for the DyIII derivative 1.
Extending the Family of N‐Heterocyclic Heavy Carbene Analogues: Synthesis and Crystal and Molecular Structures of MeN[CH2C(O)N(R)]2Sn (R = Me2NCH2CH2, PhCH2, Me3CCH2)
Authors: Iovkova‐Berends Ljuba , Seiger Miriam , Westfeld Thomas , Hoffmann Alexander , Herres‐Pawlis Sonja , Jurkschat Klaus
Published: November 2013

Invited for the cover of this issue is the group of Klaus Jurkschat at Technische Universität Dortmund. The cover image shows cyclic diazastannylenes reported by Hahn et al., Russel et al., Zaitsev et al., and Jurkschat et al., which have intramolecular donor→Sn coordination in common.
Synthesis and Comparative Study of Homoisofagomines and Analogues as Glycosidase Inhibitors
Authors: Basak Ranjan Kumar , Vankar Yashwant D.
Published: November 2013

The synthesis of polyhydroxyazepanes and their corresponding lactams has been carried out by use of Grubbs cyclisation, to yield the azepane scaffolds, as a key step. A comparative study of glycosidase inhibition by the azepanes and the corresponding lactams with varying stereochemical dispositions, number of hydroxy groups, and side chain structures was carried out.
Chemoenzymatic Synthesis of Enantiomerically Pure syn‐Configured 1‐Aryl‐3‐methylisochroman Derivatives
Authors: Simon Robert C. , Busto Eduardo , Richter Nina , Belaj Ferdinand , Kroutil Wolfgang
Published: November 2013

A two‐step synthesis of various enantiomerically pure 1‐aryl‐3‐methylisochroman derivatives was accomplished through asymmetric biocatalytic ketone reduction followed by an oxa‐Pictet–Spengler reaction. The compounds were obtained in good to excellent yield (47–92 %) in favor of the syn diastereomers [dr (syn/anti) up to 99:1]. Enantiopure arylpropanols serving as pronucleophiles for the C–C bond‐formation step were obtained by biocatalytic reduction by employing enantiocomplementary alcohol dehydrogenases, which gave access to the (S) and (R) enantiomer with up to >99 % conversion and up to >99 % ee.
Simple Electrodeposition of Dendritic Pd Without Supporting Electrolyte and Its Electrocatalytic Activity Toward Oxygen Reduction and H2O2 Sensing
Authors: Kang Minkyung , Yang Yejin , Shim Jun Ho , Lee Sang Cheol , Lee Youngmi , Lee Chongmok
Published: November 2013

Metallic palladium (Pd) electrocatalysts for oxygen reduction and hydrogen peroxide (H2O2) oxidation/reduction are prepared via electroplating on a gold metal substrate from dilute (5 to 50 mM) aqueous K2PdCl4 solution. The best Pd catalyst layer possessing dendritic nanostructures is formed on the Au substrate surface from 50 mM Pd precursor solution (denoted as Pd‐50) without any additional salt, acid or Pd templating chemical species. The Pd‐50 consisted of nanostructured dendrites of polycrystalline Pd metal and micropores within the dendrites which provide high catalyst surface area and further facilitate reactant mass transport to the catalyst surface. The electrocatalytic activity of Pd‐50 proved to be better than that of a commercial Pt (Pt/C) in terms of lower overpotential for the onset and half‐wave potentials and a greater number of electrons (n) transferred. Furthermore, amperometric i–t curves of Pd‐50 for H2O2 electrochemical reaction show high sensitivities (822.2 and −851.9 µA mM−1 cm−2) and low detection limits (1.1 and 7.91 µM) based on H2O2 oxidation H2O2 reduction, respectively, along with a fast response (<1 s).
Speciation analysis of lead in marine animals by using capillary electrophoresis couple online with inductively coupled plasma mass spectrometry
Authors: Chen Yiquan , Huang Limei , Wu Weihua , Ruan Yajuan , Wu Zujian , Xue Zhimin , Fu FengFu
Published: November 2013

We herein reported a environment‐friendly microwave‐assisted extraction used to extract trace lead compounds from marine animals and a ultrasensitive method for the analysis of Pb2+, trimethyl lead chloride (TML) and triethyl lead chloride (TEL) by using CE‐ICP‐MS. The extraction method is simple and has a high extracting efficiency. It can be used to completely extract both inorganic lead and organolead in marine animal samples without altering its species. The analytical method has a detection limit as low as 0.012–0.084 ng Pb/mL for Pb2+, TML, and TEL, and can be used to determine ultratrace Pb2+, TML, and TEL in marine animals directly without any preconcentration. With the help of above methods, we have successfully determined Pb2+, TML, and TEL in clam and oyster tissue within 20 min with a RSD (n = 6) < 5% and a recovery of 91–104%. Our results showed that Pb2+ was the main species of lead in clam and oyster, and organolead (TML) was only found in oyster. The proposed method provides a realistic approach for the accurate evaluation of lead pollution in seafood.
Rapid LC‐MS method for the detection of common fragrances in personal care products without sample preparation
Authors: Famiglini Giorgio , Termopoli Veronica , Palma Pierangela , Capriotti Fabiana , Cappiello Achille
Published: November 2013

An LC‐MS method for the analysis of personal care and household products without sample preparation is presented. The method takes advantage of the Direct‐electron ionization (EI) LC‐MS interface for the quantitation of principal components, as well as for the identification of unknown or undeclared ingredients. The technique has proven its inertness toward matrix effects and the electron ionization allows quantitation and library identification. Commercially available products (shower gel, perfume, and hand cream) were diluted with methanol and injected directly into a nano‐LC column. Limonene, linalool, and citral were selected as target compounds because of their use as fragrances in toiletry and detergent products. These and all other fragrances are commonly determined with GC‐MS analysis, prior to sample cleanup, a procedure that can lead to analytes loss. The selected compounds are not detected with ESI because of their poor or very low response. Figures of merit and validation studies were executed and special attention was devoted to matrix‐effects evaluation, because a sample preparation procedure is not involved. No matrix effects were observed, and the repeatability was excellent even after several weeks of operation. Products composition was investigated in full scan mode to determine the presence of unknown or not listed ingredients.
Quantitative assessment of the dose–response of alkylating agents in DNA repair proficient and deficient ames tester strains
Authors: Tang Leilei , Guérard Melanie , Zeller Andreas
Published: November 2013

Mutagenic and clastogenic effects of some DNA damaging agents such as methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) have been demonstrated to exhibit a nonlinear or even “thresholded” dose–response in vitro and in vivo. DNA repair seems to be mainly responsible for these thresholds. To this end, we assessed several mutagenic alkylators in the Ames test with four different strains of Salmonella typhimurium: the alkyl transferases proficient strain TA1535 (Ogt+/Ada+), as well as the alkyl transferases deficient strains YG7100 (Ogt+/Ada−), YG7104 (Ogt−/Ada+) and YG7108 (Ogt−/Ada−). The known genotoxins EMS, MMS, temozolomide (TMZ), ethylnitrosourea (ENU) and methylnitrosourea (MNU) were tested in as many as 22 concentration levels. Dose–response curves were statistically fitted by the PROAST benchmark dose model and the Lutz‐Lutz “hockeystick” model. These dose–response curves suggest efficient DNA‐repair for lesions inflicted by all agents in strain TA1535. In the absence of Ogt, Ada is predominantly repairing methylations but not ethylations. It is concluded that the capacity of alkyl‐transferases to successfully repair DNA lesions up to certain dose levels contributes to genotoxicity thresholds. Environ. Mol. Mutagen. 55:15–23, 2014. © 2013 Wiley Periodicals, Inc.
Exceptionally strong sorption of infochemicals to activated carbon reduces their bioavailability to fish
Authors: Jonker Michiel T.O. , van Mourik Louise
Published: November 2013

The addition of activated carbon (AC) to sediments is a relatively new approach to remediate contaminated sites. Activated carbon strongly sorbs hydrophobic organic contaminants, thereby reducing their bioavailability and uptake in organisms. Because of its high sorption capacity, AC might, however, also sorb other chemicals that are not contaminants but instead have ecological functions. Examples of such compounds are infochemicals or pheromones (i.e., compounds serving as chemical inter- and intraspecies information vectors). The present study investigated the sorption of 2 known infochemicals, hypoxanthine-3-N-oxide (H3NO) and pyridine-N-oxide (PNO), to 5 different powdered ACs. Sorption isotherms of these low-molecular-weight, polar fish kairomone substances appeared highly nonlinear, with logarithmic Freundlich sorption coefficients of up to 7.6. At physiologically relevant concentrations, sorption was up to 7 to 9 orders of magnitude stronger than expected on the basis of hydrophobic forces only (i.e., the compounds' log octanol–water partition coefficient, being approximately –1), indicating exceptionally strong binding to specific sites. This binding effectively reduced the bioavailability of H3NO to Sarasa goldfish, as was shown in a behavioral assay. The present study demonstrates the previously unrecognized potential of AC to sorb ecologically relevant chemicals. Whether this potential may lead to subtle, unwanted ecological effects in the field will have to be investigated in more detail during future research. Environ Toxicol Chem 2014;33:493–499. © 2013 SETAC
Biological responses of marine flatfish exposed to municipal wastewater effluent
Authors: Vidal-Dorsch Doris E. , Bay Steven M. , Greenstein Darrin J. , Baker Michael E. , Hardiman Gary , Reyes Jesus A. , Kelley Kevin M. , Schlenk Daniel
Published: November 2013

There is increasing concern over the presence of pharmaceutical compounds, personal care products, and other chemicals collectively known as contaminants of emerging concern (CECs) in municipal effluents, yet knowledge of potential environmental impacts related to these compounds is still limited. The present study used laboratory exposures to examine estrogenic, androgenic, and thyroid-related endocrine responses in marine hornyhead turbot (Pleuronichthys verticalis) exposed to CECs from municipal effluents with 2 degrees of treatment. Fish were exposed for 14 d to environmentally realistic concentrations of effluent (0.5%) and to a higher concentration (5%) to investigate dose responses. Plasma concentrations of estradiol (E2), vitellogenin (VTG), 11-keto testosterone, and thyroxine were measured to assess endocrine responses. Contaminants of emerging concern were analyzed to characterize the effluents. Diverse types of effluent CECs were detected. Statistically significant responses were not observed in fish exposed to environmentally realistic concentrations of effluent. Elevated plasma E2 concentrations were observed in males exposed to ammonia concentrations similar to those found in effluents. However, exposure to ammonia did not induce VTG production in male fish. The results of the present study highlight the importance of conducting research with sentinel organisms in laboratory studies to understand the environmental significance of the presence of CECs in aquatic systems. Environ Toxicol Chem 2014;33:583–591. © 2013 SETAC
The vas::egfp transgenic zebrafish: A practical model for studies on the molecular mechanisms by which environmental estrogens affect gonadal sex differentiation
Authors: Filby Amy L. , Ortiz-Zarragoitia Maren , Tyler Charles R.
Published: November 2013

The vas::egfp transgenic zebrafish (Danio rerio) could significantly enhance studies on the mechanisms by which environmental estrogens disrupt sexual differentiation, because the developing gonad can be visualized during early life via fluorescence detection. There are methodological challenges regarding dissecting out the gonads in early-life-stage fish, however, and transgene responses to estrogen exposure have not been tested. The authors exposed vas::egfp transgenic zebrafish and their wild-type siblings to the model estrogen 17α-ethinylestradiol (EE2; 0.62 ng/L and 3.33 ng/L measured concentrations) during sexual development (20−60 d posthatch) and used enhanced green fluorescent protein (egfp) fluorescence to identify and dissect single gonads (at 40 d posthatch) to provide sufficient RNA for individual gene expression analyses, retaining the remaining gonad in the body cavity for histological analyses of sex and stage of development. Genotyping confirmed that all transgenic control fish were phenotypically egfp positive (showed green fluorescence). Interestingly, however, in a few transgenic fish exposed to EE2, no phenotypic egfp signal was seen, most notably for the 3.33 ng/L EE2 exposure. It was subsequently found that gonadal vasa expression was reduced by this concentration of EE2. Hepatic vitellogenin expression demonstrated that the vas::egfp and wild-type lines responded to estrogen with an equivalent sensitivity. The authors conclude that the vas::egfp zebrafish provides an enhanced and practical system for mechanistic studies on the effects of environmentally relevant concentrations of estrogens on gonad development. Environ Toxicol Chem 2014;33:602–605. © 2013 SETAC
Electrochemical Test Procedures for Accelerated Evaluation of Fuel Cell Cathode Catalyst Degradation
Authors: Marcu A. , Toth G. , Behm R. J.
Published: November 2013

The paper introduces an accelerated test procedure that was developed to evaluate the cathode catalyst stability. It is based on systematic analysis of square wave cycles (SWC) in comparison to triangular wave cycles (TWC). Two voltage windows were used: (i) 0.6–0.9 V to simulate the fuel cell drive cycles and (ii) 0.6–1.2 V to accelerate the test. When simulating the drive cycles over 6,000 h, an estimated loss of 40% in electrochemical surface area (ECSA) is found. Increasing the potential window, the testing time could be reduced to 20 h for TWC and for SWC to 4 h.
Hybrid Network Sulfonated Polynorbornene/Silica Membranes with Enhanced Proton Conductivity by Doped Phosphotungstic Acid
Authors: He X.‐H. , Zheng Y. , Yao H.‐L. , Chen Y.‐W. , Chen D.‐F.
Published: November 2013

A series of novel hybrid sulfonated polynorbornene‐silica (PBN–SiO2) proton conducting membranes doped with different weight ratio of phosphotungstic acid (PWA) were prepared by the casting procedure. The proton conductivity of the composite membranes containing 40 wt.% PWA reached the maximum of 6.1 × 10–2 S cm–1 and increased gradually with PWA content and temperature elevating, while the methanol permeabilities (3.52–9.39 × 10–7 cm2 s–1) of these membranes were much lower than that of Nafion 117 (2.36 × 10–6 cm2 s–1). The membranes also exhibited excellent thermally stable and mechanical properties, which imply that the PBN–SiO2–PWA membranes are promising materials in the direct methanol fuel cells (DMFC) applications.
Detecting Rare Haplotype‐Environment Interaction With Logistic Bayesian LASSO
Authors: Biswas Swati , Xia Shuang , Lin Shili
Published: November 2013

Two important contributors to missing heritability are believed to be rare variants and gene‐environment interaction (GXE). Thus, detecting GXE where G is a rare haplotype variant (rHTV) is a pressing problem. Haplotype analysis is usually the natural second step to follow up on a genomic region that is implicated to be associated through single nucleotide variants (SNV) analysis. Further, rHTV can tag associated rare SNV and provide greater power to detect them than popular collapsing methods. Recently we proposed Logistic Bayesian LASSO (LBL) for detecting rHTV association with case–control data. LBL shrinks the unassociated (especially common) haplotypes toward zero so that an associated rHTV can be identified with greater power. Here, we incorporate environmental factors and their interactions with haplotypes in LBL. As LBL is based on retrospective likelihood, this extension is not trivial. We model the joint distribution of haplotypes and covariates given the case–control status. We apply the approach (LBL‐GXE) to the Michigan, Mayo, AREDS, Pennsylvania Cohort Study on Age‐related Macular Degeneration (AMD). LBL‐GXE detects interaction of a specific rHTV in CFH gene with smoking. To the best of our knowledge, this is the first time in the AMD literature that an interaction of smoking with a specific (rather than pooled) rHTV has been implicated. We also carry out simulations and find that LBL‐GXE has reasonably good powers for detecting interactions with rHTV while keeping the type I error rates well controlled. Thus, we conclude that LBL‐GXE is a useful tool for uncovering missing heritability.
FAM3A Activates PI3K p110α/Akt Signaling to Ameliorate Hepatic Gluconeogenesis and Lipogenesis
Authors: Wang Chunjiong , Chi Yujing , Li Jing , Miao Yifei , Li Sha , Su Wen , Jia Shi , Chen Zhenzhen , Du Shengnan , Zhang Xiaoyan , Zhou Yunfeng , Wu Wenhan , Zhu Mingyan , Wang Zhiwei , Yang Huaqian , Xu Guoheng , Wang Shiqiang , Yang Jichun , Guan Youfei
Published: November 2013

FAM3A belongs to a novel cytokine-like gene family, and its physiological role remains largely unknown. In our study, we found a marked reduction of FAM3A expression in the livers of db/db and high-fat diet (HFD)-induced diabetic mice. Hepatic overexpression of FAM3A markedly attenuated hyperglycemia, insulin resistance, and fatty liver with increased Akt (pAkt) signaling and repressed gluconeogenesis and lipogenesis in the livers of those mice. In contrast, small interfering RNA (siRNA)-mediated knockdown of hepatic FAM3A resulted in hyperglycemia with reduced pAkt levels and increased gluconeogenesis and lipogenesis in the livers of C57BL/6 mice.

In vitro

study revealed that FAM3A was mainly localized in the mitochondria, where it increases adenosine triphosphate (ATP) production and secretion in cultured hepatocytes. FAM3A activated Akt through the p110α catalytic subunit of PI3K in an insulin-independent manner. Blockade of P2 ATP receptors or downstream phospholipase C (PLC) and IP3R and removal of medium calcium all significantly reduced FAM3A-induced increase in cytosolic free Ca2+ levels and attenuated FAM3A-mediated PI3K/Akt activation. Moreover, FAM3A-induced Akt activation was completely abolished by the inhibition of calmodulin (CaM).

Conclusion :

FAM3A plays crucial roles in the regulation of glucose and lipid metabolism in the liver, where it activates the PI3K-Akt signaling pathway by way of a Ca2+/CaM-dependent mechanism. Up-regulating hepatic FAM3A expression may represent an attractive means for the treatment of insulin resistance, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD). (Hepatology 2014;59:1779–1790)
The circadian rest‐activity rhythm, a potential safety pharmacology endpoint of cancer chemotherapy
Authors: Ortiz‐Tudela Elisabet , Iurisci Ida , Beau Jacques , Karaboue Abdoulaye , Moreau Thierry , Rol Maria Angeles , Madrid Juan Antonio , Lévi Francis , Innominato Pasquale F.
Published: November 2013

The robustness of the circadian timing system (CTS) was correlated to quality of life and predicted for improved survival in cancer patients. However, chemotherapy disrupted the CTS according to dose and circadian timing in mice. A continuous and repeated measures longitudinal design was implemented here to characterize CTS dynamics in patients receiving a fixed circadian‐based chemotherapy protocol. The rest‐activity rhythm of 49 patients with advanced cancer was monitored using a wrist actigraph for 13 days split into four consecutive spans of 3–4 days each, i.e., before, during, right after and late after a fixed chronotherapy course. The relative amount of activity in bed vs. out of bed (I<O, main endpoint), the autocorrelation coefficient r24, the relative 24‐hr amplitude (Amp), interdaily stability (IS) and intradaily variability (IV) were compared according to study span. Circadian disruption (I<O ≤ 97.5%) resulted from the administration of the fixed chronotherapy protocols, with all five rest‐activity rhythm parameters being worsened in the whole group of patients (p < 0.05). Mean parameter values subsequently recovered to near baseline values. The occurrence of circadian disruption on chemotherapy was associated with a higher risk of clinically relevant fatigue (p = 0.028) or body weight loss (p = 0.05). Four CTS dynamic patterns characterized treatment response including no change (9.5% of the patients); improvement (14.3%); alteration and complete recovery (31%) or sustained deterioration (45%), possibly due to inadequate chronotherapy dosing and/or timing. Improved clinical tolerability could result from the minimization of circadian disruption through the personalization of chronotherapy delivery.
Yin and yang of tumor inflammation: How innate immune suppressors shape the tumor microenvironments
Authors: Jinushi Masahisa
Published: November 2013

Pattern recognition‐mediated sensing systems direct host immunity towards either antitumor immunosurveillance or protumorigenic inflammation. These activities imply dual and conflicting roles in the regulation of tumor‐associated inflammation. On the one hand, recent evidence has revealed that several signaling components and cell‐surface receptors suppress innate immune signals and constitute a negative feedback machinery preventing excess and continuous inflammation within tumor microenvironments. On the other hand, these same components also negatively regulate intrinsic tumorigenic activities by targeting nuclear factor‐kappaB (NF‐κB)‐mediated antiapoptotic and inflammatory signals. Furthermore, the activation status of innate immune suppressors may reflect the functional plasticity of interactions between tumor cells and innate immune cells and determine whether tumor inflammation supports anti‐ or pro‐tumorigenic responses. Thus, innate immune suppressors may provide valuable information about the immunogenic or tumorigenic status of tumor‐associated inflammation thereby serving as potential biomarkers that predict tumor progression. Comprehensive analysis for identifying general and unique features of each innate immune suppressor in the regulation of tumor inflammation should explore the development of new biomarkers for improving future therapeutic strategies.
Tissue-Level Mechanisms Responsible for the Increase in Bone Formation and Bone Volume by Sclerostin Antibody
Authors: Ominsky Michael S , Niu Qing-Tian , Li Chaoyang , Li Xiaodong , Ke Hua Zhu
Published: November 2013

Bone formation can be remodeling-based (RBF) or modeling-based (MBF), the former coupled to bone resorption and the latter occurring directly on quiescent surfaces. Unlike osteoanabolic therapies such as parathyroid hormone (PTH) 1-34 that increase bone remodeling and thus both formation and resorption, sclerostin antibody (Scl-Ab) increases bone formation while decreasing bone resorption. With this unique profile, we tested our hypothesis that Scl-Ab primarily elicited MBF by examining bones from Scl-Ab–treated ovariectomized (OVX) rats and male cynomolgus monkeys (cynos). Histomorphometry was performed to quantify and characterize bone surfaces in OVX rats administered vehicle or Scl-Ab (25 mg/kg) subcutaneously (sc) twice/week for 5 weeks and in adolescent cynos administered vehicle or Scl-Ab (30 mg/kg) sc every 2 weeks for 10 weeks. Fluorochrome-labeled surfaces in L2 vertebra and femur endocortex (cynos only) were considered to be MBF or RBF based on characteristics of their associated cement lines. In OVX rats, Scl-Ab increased MBF by eightfold (from 7% to 63% of bone surface, compared to vehicle). In cynos, Scl-Ab markedly increased MBF on trabecular (from 0.6% to 34%) and endocortical surfaces (from 7% to 77%) relative to vehicle. Scl-Ab did not significantly affect RBF in rats or cynos despite decreased resorption surface in both species. In cynos, Scl-Ab resulted in a greater proportion of RBF and MBF containing sequential labels from week 2, indicating an increase in the lifespan of the formative site. This extended formation period was associated with robust increases in the percent of new bone volume formed. These results demonstrate that Scl-Ab increased bone volume by increasing MBF and prolonged the formation period at both modeling and remodeling sites while reducing bone resorption. Through these unique effects on bone formation and resorption, Scl-Ab may prove to be an effective therapeutic to rapidly increase bone mass in diseases such as osteoporosis. © 2014 American Society for Bone and Mineral Research.
Algorithms for computer detection of symmetry elements in molecular systems
Authors: Beruski Otávio , Vidal Luciano N.
Published: November 2013

Simple procedures for the location of proper and improper rotations and reflexion planes are presented. The search is performed with a molecule divided into subsets of symmetrically equivalent atoms (SEA) which are analyzed separately as if they were a single molecule. This approach is advantageous in many aspects. For instance, in those molecules that are symmetric rotors, the number of atoms and the inertia tensor of the SEA provide one straight way to find proper rotations of any order. The algorithms are invariant to the molecular orientation and their computational cost is low, because the main information required to find symmetry elements is interatomic distances and the principal moments of the SEA. For example, our Fortran implementation, running on a single processor, took only a few seconds to locate all 120 symmetry operations of the large and highly symmetrical fullerene
, belonging to the Ih point group. Finally, we show how the interatomic distances matrix of a slightly unsymmetrical molecule is used to symmetrize its geometry. © 2013 Wiley Periodicals, Inc.