bluuebunny/crossref_metadata_2025_split huggingface dataset:
Geo‐effectiveness and radial dependence of magnetic cloud erosion by magnetic reconnection
Authors: Lavraud Benoit , Ruffenach Alexis , Rouillard Alexis P. , Kajdic Primoz , Manchester Ward B. , Lugaz Noé 
Published: December 2013

Key PointsMC erosion has a significant impact on geo‐effectivenessCombined importance of erosion and compression on geo‐effectivenessMeasured reconnection rates are consistent with observed erosion
Formation and evolution of biogenic secondary organic aerosol over a forest site in Japan
Authors: Han Yuemei , Iwamoto Yoko , Nakayama Tomoki , Kawamura Kimitaka , Mochida Michihiro 
Published: December 2013

AbstractChemical composition of atmospheric aerosol particles was characterized using an Aerodyne high‐resolution time‐of‐flight aerosol mass spectrometer at a forest site in Japan during 20–30 August 2010. A major fraction of nonrefractory submicron aerosol particles consisted of organics (accounting for, on average, 46% of total mass), sulfate (41%), and ammonium (12%). Positive matrix factorization of high‐resolution organic aerosol mass spectra identified two oxygenated organic aerosol (OOA) components: a highly oxidized, low‐volatility OOA and a less oxidized, semivolatile OOA (SV‐OOA), interpreted mainly as aged regional organic aerosol (OA) and as locally formed biogenic secondary OA (BSOA), respectively. The mass concentrations of SV‐OOA increased prominently during the daytime, suggesting a strong photochemical production of BSOA on both nonevent and new particle formation event days. Increases of f44 (fraction of m/z 44 in OA mass spectrum), the fraction of CxOy+ fragment, and the O/C ratio after midday (around 13:00 local time) suggest that OA became increasingly oxygenated, which can be explained by the aging of freshly formed BSOA. Aqueous phase oxidation reactions under conditions of high relative humidity may have played a vital role in the aging of BSOA in this forest atmosphere. A substantial increase of the mass concentration of organics in the small size range (below 300 nm in vacuum aerodynamic diameter), without an increase in that of sulfate, suggests that the formation of BSOA made a dominant contribution to the presence of particles of cloud condensation nuclei size around the studied area.
Nickel‐ or Palladium‐Catalyzed Stereoselective Synthesis of Tetrasubstituted Olefinic Indolines‐Fused Triazoles: Extension to the Spiroindoline Core
Authors: Senadi Gopal Chandru , Hu Wan‐Ping , Boominathan Siva Senthil Kumar , Wang Jeh‐Jeng 
Published: December 2013

AbstractA nickel‐ or palladium‐catalyzed cascade approach to afford indolines‐fused triazoles with tetrasubstituted olefins in good yields with excellent control of regio‐ and stereoselectivity is described. We have also discussed the synthesis of unsaturated carbonyl species when the alkyne was appended to an alkyl chain. The synthetic methodology has been extended to construct the biologically active spiroindoline core via a vinylcylopropane (VCP) intermediate. The synthesized tetrasubstituted scaffolds were investigated for their photophysical properties and all of the them exhibited good absorption and fluorescence emission in the UV‐visible region.magnified image
Synthesis and properties of fluorescent light‐emitting polyamide hybrids with reactive nanosilica by epoxide functionalization
Authors: Alizadeh Raouf , Ghaemy Mousa , Bazzar Maasoomeh , Hashemi Nasr Farzaneh 
Published: December 2013

AbstractA series of poly(carbazole‐quinoxaline‐amide)s (PCQAs) containing phenyl and long alkyl chain as pendants was synthesized from polycondensation between a new diamine with a synthesized and several commercial dicarboxylic acids using Yamazaki's method. PCQAs had inherent viscosities and weight average molecular weights (
) in the range of 0.48–0.62 dL g−1 and 51,600–58,500 g mol−1, respectively. These luminescent polymers are readily soluble in a variety of organic solvents and formed low‐colored and tough thin films. In this study, silane modified SiO2 (mSiO2) nanoparticles were prepared, characterized and used with PCQAs in preparation of nanocomposites via solution blending method. The interfacial interaction strength between mSiO2 and the polymer–matrix enhanced thermal stability (T10%, from 463°C to 500°C) and mechanical strength (from 100 MPa to 150 MPa) for composite containing 30 wt % mSiO2 in comparison with the pure polyamide. These materials showed good ability for extraction–elimination of metal ions such as Cr6+, Cr3+, Co2+, Zn2+, Pb2+, Cd2+, and Hg2+ from aqueous solutions either individually or in the mixture at various pH. © 2013 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2014, 131, 40219.
Dynamic transcriptional response of Escherichia coli to inclusion body formation
Authors: Baig Faraz , Fernando Lawrence P. , Salazar Mary Alice , Powell Rhonda R. , Bruce Terri F. , Harcum Sarah W. 
Published: December 2013

ABSTRACTEscherichia coli is used intensively for recombinant protein production, but one key challenge with recombinant E. coli is the tendency of recombinant proteins to misfold and aggregate into insoluble inclusion bodies (IBs). IBs contain high concentrations of inactive recombinant protein that require recovery steps to salvage a functional recombinant protein. Currently, no universally effective method exists to prevent IB formation in recombinant E. coli. In this study, DNA microarrays were used to compare the E. coli gene expression response dynamics to soluble and insoluble recombinant protein production. As expected and previously reported, the classical heat‐shock genes had increased expression due to IB formation, including protein folding chaperones and proteases. Gene expression levels for protein synthesis‐related and energy‐synthesis pathways were also increased. Many transmembrane transporter and corresponding catabolic pathways genes had decreased expression for substrates not present in the culture medium. Additionally, putative genes represented over one‐third of the genes identified to have significant expression changes due to IB formation, indicating many important cellular responses to IB formation still need to be characterized. Interestingly, cells grown in 3% ethanol had significantly reduced gene expression responses due to IB formation. Taken together, these results indicate that IB formation is complex, stimulates the heat‐shock response, increases protein and energy synthesis needs, and streamlines transport and catabolic processes, while ethanol diminished all of these responses. Biotechnol. Biotechnol. Bioeng. 2014;111: 980–999. © 2014 Wiley Periodicals, Inc.
Microbially synthesized modular virus‐like particles and capsomeres displaying group A streptococcus hypervariable antigenic determinants
Authors: Chuan Yap P. , Wibowo Nani , Connors Natalie K. , Wu Yang , Hughes Fiona K. , Batzloff Michael R. , Lua Linda H.L. , Middelberg Anton P.J. 
Published: December 2013

ABSTRACTEffective and low‐cost vaccines are essential to control severe group A streptococcus (GAS) infections prevalent in low‐income nations and the Australian aboriginal communities. Highly diverse and endemic circulating GAS strains mandate broad‐coverage and customized vaccines. This study describes an approach to deliver cross‐reactive antigens from endemic GAS strains using modular virus‐like particle (VLP) and capsomere systems. The antigens studied were three heterologous N‐terminal peptides (GAS1, GAS2, and GAS3) from the GAS surface M‐protein that are specific to endemic strains in Australia Northern Territory Aboriginal communities. In vivo data presented here demonstrated salient characteristics of the modular delivery systems in the context of GAS vaccine design. First, the antigenic peptides, when delivered by unadjuvanted modular VLPs or adjuvanted capsomeres, induced high titers of peptide‐specific IgG antibodies (over 1 × 104). Second, delivery by capsomere was superior to VLP for one of the peptides investigated (GAS3), demonstrating that the delivery system relative effectiveness was antigen‐dependant. Third, significant cross‐reactivity of GAS2‐induced IgG with GAS1 was observed using either VLP or capsomere, showing the possibility of broad‐coverage vaccine design using these delivery systems and cross‐reactive antigens. Fourth, a formulation containing three pre‐mixed modular VLPs, each at a low dose of 5 μg (corresponding to <600 ng of each GAS peptide), induced significant titers of IgGs specific to each peptide, demonstrating that a multivalent, broad‐coverage VLP vaccine formulation was possible. In summary, the modular VLPs and capsomeres reported here demonstrate, with promising preliminary data, innovative ways to design GAS vaccines using VLP and capsomere delivery systems amenable to microbial synthesis, potentially adoptable by developing countries. Biotechnol. Bioeng. 2014;111: 1062–1070. © 2013 Wiley Periodicals, Inc.
A novel platform for antibody library selection in mammalian cells based on a growth signalobody
Authors: Yoshida Rie , Kawahara Masahiro , Nagamune Teruyuki 
Published: December 2013

AbstractWhile many antibody‐screening methods in vitro have been developed, these methods need repeated cycles of panning or sorting procedures to isolate antigen‐specific antibodies. Here we developed a new antibody selection system based on antigen‐dependent growth of mammalian cells. In this system, a growth signalobody library, which is a naïve single‐chain Fv (scFv) library/cytokine receptor chimera that can transduce a growth signal in response to a specific antigen, is expressed in murine interleukin‐3‐dependent Ba/F3 cells. Simple culture of the cells in an antigen‐containing medium results in growing cells with a high‐affinity scFv gene, leading to selection of the scFv specific to the target antigen without panning/sorting procedures. To demonstrate this system, we used the SD1D2g signalobody having the signaling domain of gp130 and fluorescein‐conjugated BSA as a target antigen, and investigated whether a fluorescein‐specific scFv could be selected from a naïve scFv library. As a result, we successfully obtained fluorescein‐binding scFv clones, and the scFv clone with the highest affinity was most abundantly selected, having the same sequence as the clone, which had been obtained through phage display. These results demonstrate the utility of our system as an affinity‐based scFv selection method based on growth advantage of mammalian cells. Biotechnol. Bioeng. 2014;111: 1170–1179. © 2013 Wiley Periodicals, Inc.
Comparative pharmacokinetics study of a kaurane diterpenoid after oral administration of monomer and Siegesbeckiae pubescens Makino extract to rats
Authors: Lei Ming , Jiang Zhen , Liu Hongjiao , Cui Yan , Ye Xiaoxia , Ji Bin , Guo Xingjie 
Published: December 2013

ABSTRACTIn this paper, a sensitive, rapid and reproducible high‐performance liquid chromatography–tandem mass spectrometry method was developed to analyze 16α‐hydro‐ent‐kauran‐17,19‐dioic acid in rat plasma. First, this study compared the pharmacokinetics of 16α‐hydro‐ent‐kauran‐17,19‐dioic acid after oral administration of monomer and Siegesbeckiae pubescens Makino extract in rat plasma with approximately the same dosage of 6.0 mg/kg. Second, chromatographic separation was performed on a Waters Symmetry C18 column (2.1 × 100 mm, 3.5 µm) with isocratic elution using methanol–water containing 5 mmol/L ammonium acetate (70:30, v/v) as mobile phase at a flow rate of 0.2 mL/min. The calibration curves were linear over the range of 30–12000 ng/mL for monomer. At different time points (0, 0.083, 0.25, 0.75, 1, 2, 4, 6, 8, 12, 18, 24, 36, 48, 60 and 72 h) after administration, the concentrations of monomer in rat plasma were determined and main pharmacokinetic parameters were estimated. The double absorption presented in this study indicates that the pharmacokinetics of monomer in rat plasma have significant differences between different groups. Copyright © 2013 John Wiley & Sons, Ltd.
Aptamers Act as Activators for the Thrombin Mediated‐Hydrolysis of Peptide Substrates
Authors: Tan Xiaohong , Dey Sourav Kumar , Telmer Cheryl , Zhang Xiaoliang , Armitage Bruce A. , Bruchez Marcel P. 
Published: December 2013

AbstractThrombin is the typical target in anticlotting therapy for many serious diseases such as heart attack and stroke. DNA aptamers are well‐known thrombin inhibitors that prevent fibrinogen hydrolysis. We have discovered that exosite‐targeting antithrombin aptamers enhance the activity of thrombin toward a small peptide substrate, Sar(N‐methylglycine)‐Pro‐Arg‐paranitroanilide, and that the activation of the enzyme by these aptamers is strongly inhibited by their complementary DNAs. Our study reveals that treatment with mixed aptamers or with a dual‐aptamer construct led to an 8.6‐ or 7.8‐fold enhancement in peptide hydrolysis relative to thrombin alone, a synergistic effect much higher than the activation observed with a monofunctional aptamer (1.5‐fold for Apt27 or 2.7‐fold for Apt15). In addition, we discovered that Apt27 is a biofunctional molecule for thrombin because of its activation effect. An enzyme kinetic study indicates that the binding of aptamers to exosites I and II significantly activates thrombin towards the peptide substrate, thus illustrating that binding of aptamers to exosites can allosterically regulate the active site of thrombin. Our study suggests the necessity of considering possible side effects when DNA aptamers are used for clinical applications involving the inhibition of thrombin‐mediated clotting.
Localisation of bovine colostral odorant‐binding protein (bcOBP) mRNAs in several tissues of bovine body
Authors: Katayama Shota , Japaridze Tamar 
Published: December 2013

AbstractBovine colostral odorant‐binding protein (bcOBP) is a novel protein found in bovine colostrum and belonging to the lipocalin superfamily. Most of them are secretory proteins. We have examined the localisation of bcOBP messenger RNA in several tissues. The expression of bcOBP messenger RNAs was followed in bovine principal organs and female reproductive tracts with in situ hybridisation, but the localisation of it was not detected. The expression levels of bcOBP mRNAs were also extremely low in those tissues. On the other hand, the expression of bcOBP messenger RNAs has not been found in the airway epithelia and the gallbladder. These results suggest that bcOBP messenger RNAs are expressed in bovine several tissues without its localisation. In conclusion, the localisation of bcOBP messenger RNAs in bovine several tissues was not found.
Cyanobuta‐1,3‐dienes as Novel Electron Acceptors for Photoactive Multicomponent Systems
Authors: Tancini Francesca , Monti Filippo , Howes Kara , Belbakra Abdelhalim , Listorti Andrea , Schweizer W. Bernd , Reutenauer Philippe , Alonso‐Gómez José‐Lorenzo , Chiorboli Claudio , Urner Lorenz M. , Gisselbrecht Jean‐Paul , Boudon Corinne , Armaroli Nicola , Diederich François 
Published: December 2013

AbstractThe synthesis, electrochemical, and photophysical properties of five multicomponent systems featuring a ZnII porphyrin (ZnP) linked to one or two anilino donor‐substituted pentacyano‐ (PCBD) or tetracyanobuta‐1,3‐dienes (TCBD), with and without an interchromophoric bridging spacer (S), are reported: ZnP‐S‐PCBD (1), ZnP‐S‐TCBD (2), ZnP‐TCBD (3), ZnP‐(S‐PCBD)2 (4), and ZnP‐(S‐TCBD)2 (5). By means of steady‐state and time‐resolved absorption and luminescence spectroscopy (RT and 77 K), photoinduced intramolecular energy and electron transfer processes are evidenced, upon excitation of the porphyrin unit. In systems equipped with the strongest acceptor PCBD and the spacer (1, 4), no evidence of electron transfer is found in toluene, suggesting ZnP→PCBD energy transfer, followed by ultrafast (<10 ps) intrinsic deactivation of the PCBD moiety. In the analogous systems with the weaker acceptor TCBD (2, 5), photoinduced electron transfer occurs in benzonitrile, generating a charge‐separated (CS) state lasting 2.3 μs. Such a long lifetime, in light of the high Gibbs free energy for charge recombination (ΔGCR=−1.39 eV), suggests a back‐electron transfer process occurring in the so‐called Marcus inverted region. Notably, in system 3 lacking the interchromophoric spacer, photoinduced charge separation followed by charge recombination occur within 20 ps. This is a consequence of the close vicinity of the donor–acceptor partners and of a virtually activationless electron transfer process. These results indicate that the strongly electron‐accepting cyanobuta‐1,3‐dienes might become promising alternatives to quinone‐, perylenediimide‐, and fullerene‐derived acceptors in multicomponent modules featuring photoinduced electron transfer.
ChemInform Abstract: Size‐Controlled Chevrel Mo6S8 as Cathode Material for Mg Rechargeable Battery.
Authors: Ryu Anna , Park Min‐Sik , Cho Woosuk , Kim Jeom‐Soo , Kim Young‐Jun 
Published: December 2013

AbstractCuMo3S4 powders are prepared by the molten salt method from mixtures of CuS, Mo, MoS2, and different amounts of KCl (alumina crucible, 850 °C, 60 h).
ChemInform Abstract: Crystal Growth of New Hexahydroxometallates Using a Hydroflux.
Authors: Chance W. Michael , Bugaris Daniel E. , Sefat Athena S. , zur Loye Hans‐Conrad 
Published: December 2013

AbstractSingle crystals of the new compounds Sr2Mn(OH)6, Ba2Mn(OH)6, Sr2Co(OH)6, Ba2Co(OH)6, Sr2Ni(OH)6, Ba2Ni(OH)6, and Ba2Cu(OH)6 are prepared from M(OH)2 (M: Sr, Ba) and MnCl2, CoCl2, Ni(NO3)2, or CuO using a combination of water with NaOH, KOH, or a NaOH/KOH mixture as hydroflux (180—230 °C, 12—36 h).
ChemInform Abstract: Thallium Mercury Chalcobromides, TlHg6Q4Br5 (Q: S, Se).
Authors: Wibowo Arief C. , Malliakas Christos D. , Chung Duck Young , Im Jino , Freeman Arthur J. , Kanatzidis Mercouri G. 
Published: December 2013

AbstractThe new compounds TlHg6S4Br5 and TlHg6Se4Br5 are synthesized from mixtures of HgQ (Q: S, Se), HgBr2, and TlBr (sealed silica tubes, 200 °C, 12 resp.
ChemInform Abstract: Heterodinuclear Lanthanoid‐Containing Polyoxometalates: Stepwise Synthesis and Single‐Molecule Magnet Behavior.
Authors: Sato Rinta , Suzuki Kosuke , Sugawa Midori , Mizuno Noritaka 
Published: December 2013

AbstractHeterodinuclear lanthanoid cores are synthesized through stepwise incorporation of two types of lanthanoid cations into the vacant sites of lacunary [γ‐SiW10O36]8‐ units without the use of templating cations.
ChemInform Abstract: A Novel Chain Structure Constructed from Copper Complexes and Dimers Based on Bi‐Capped Keggin Clusters.
Authors: Cui Xiao‐Bing , et al. et al. 
Published: December 2013

AbstractThe new compound [Cu(en)2][Cu(en)2(H2O)]2 [SiMo8V6O42] [Cu(en)2]·1.5H2O is hydrothermally synthesized from a mixture of Na2MoO4, V2O5, Na2SiO3, CuCl2, H2C2O4, en, and H2O (autoclave, pH 7, 180 °C, 3 d; 73% yield).
ChemInform Abstract: ChenPhos: Highly Modular P‐Stereogenic C1‐Symmetric Diphosphine Ligands for the Efficient Asymmetric Hydrogenation of α‐Substituted Cinnamic Acids.
Authors: Chen Weiping , Spindler Felix , Pugin Benoit , Nettekoven Ulrike 
Published: December 2013

AbstractSeveral chiral Chenphos‐ligands are synthesized and tested in a model reaction.
ChemInform Abstract: Selective Deprotection of TBDMS Alkyl Ethers in the Presence of TIPS or TBDPS Phenyl Ethers by Catalytic CuSO4·5H2O in Methanol.
Authors: Gonzalez‐Calderon Davir , Benitez‐Puebla Luis J. , Gonzalez‐Gonzalez Carlos A. , Assad‐Hernandez Salomon , Fuentes‐Benitez Aydee , Cuevas‐Yanez Erick , Corona‐Becerril David , Gonzalez‐Romero Carlos 
Published: December 2013

AbstractThe cleavage of Tbs‐ethers is efficiently achieved in methanol with CuSO4 as the catalyst.
ChemInform Abstract: Widely Applicable Synthesis of Enantiomerically Pure Tertiary Alkyl‐Containing 1‐Alkanols by Zirconium‐Catalyzed Asymmetric Carboalumination of Alkenes and Palladium‐ or Copper‐Catalyzed Cross‐Coupling.
Authors: Xu Shiqing , Lee Ching‐Tien , Wang Guangwei , Negishi Ei‐ichi 
Published: December 2013

AbstractEither enantiomer of the desired alcohols can be readily obtained with very high optical purity.
ChemInform Abstract: Asymmetric Synthesis of Unnatural Amino Acids and Tamsulosin Chiral Intermediate.
Authors: Arava Veera Reddy , Amasa Srinivasulu Reddy , Bhatthula Bharat Kumar Goud , Kompella Laxmi Srinivas , Matta Venkata Prasad , Subha M. C. S. 
Published: December 2013

AbstractAn efficient, enantioselective hydrogenation of N‐acetylamino acrylic acids (I) is developed and successfully applied to the synthesis of the chiral key intermediate (III) of the antihypertensive drug tamsulosin.
ChemInform Abstract: Enantioselective Catalytic Transannular Ketone—Ene Reactions.
Authors: Rajapaksa Naomi S. , Jacobsen Eric N. 
Published: December 2013

AbstractA novel chromium(III) triflate tridentate Schiff base complex is efficiently utilized for a highly enantio‐ and diastereoselective transannular ketone‐ene reaction of electronically unactivated keto‐olefins (I) and (III) to afford enantioenriched bicyclic alcohols.
ChemInform Abstract: Organocatalytic Asymmetric Direct Aldol Reaction of Pyruvic Aldehyde Dimethyl Acetal with Isatin Derivatives.
Authors: Kumar Akshay , Chimni Swapandeep Singh 
Published: December 2013

AbstractA highly enantioselective approach for the synthesis of the compounds (III) and (V) by the title reaction is developed.
ChemInform Abstract: Phoshine‐Free Thiopseudourea‐Pd(II) Complex Catalyzed Larock Heteroannulation of 2‐Haloamines with Internal Alkynes.
Authors: Srinivas Keesara , Saiprathima Parvathaneni , Balaswamy Kodicherla , Rao Mandapati Mohan 
Published: December 2013

AbstractLow loadings of the title catalyst are sufficient to give access to different substituted indole derivatives.
ChemInform Abstract: Bifunctional Squaramide‐Catalyzed One‐Pot Sequential Michael Addition/Dearomative Bromination: Convenient Access to Optically Active Brominated Pyrazol‐5(4H)‐ones with Adjacent Quaternary and Tertiary Stereocenters.
Authors: Wang Huanxia , Wang Youming , Song Haibin , Zhou Zhenghong , Tang Chuchi 
Published: December 2013

AbstractAn organocatalytic asymmetric simple process affords a wide variety of the title compounds in high yields with good to excellent diastereoselectivity and uniformly high levels of enantioselectivity from readily available starting materials.
ChemInform Abstract: Catalytic Enantioselective Iodoetherification of Oximes.
Authors: Tripathi Chandra Bhushan , Mukherjee Santanu 
Published: December 2013

AbstractThis is the first catalytic asymmetric iodoetherification of oximes yielding isoxazolines containing quarternary stereocenters in high yields with good enantioselectivities.
ChemInform Abstract: Pd‐Catalyzed Heteroarylations of 3‐Bromochromen‐4‐one via C—H Bond Activation of Heteroarenes.
Authors: Belkessam Fatma , Derridj Fazia , Zhao Liqin , Elias Abdelhamid , Aidene Mohand , Djebbar Saffia , Doucet Henri 
Published: December 2013

AbstractThe title method is applicable to a wide variety of heteroaromatics and tolerates a range of functional groups.
ChemInform Abstract: Synthesis of Novel 2H,8H‐Pyrano[2,3‐f]chromene‐2,8‐diones from 8‐Formyl‐7‐hydroxy‐4‐methylcoumarin.
Authors: Al‐Kawkabani Ahmed , Boutemeur‐Kheddis Baya , Makhloufi‐Chebli Malika , Hamdi Maamar , Talhi Oualid , Silva Artur M. S. 
Published: December 2013

AbstractThe synthesis of 8‐formyl‐7‐hydroxy‐4‐methylcoumarin (III) is developed and the condensation with various activated methylene compounds is demonstrated.
ChemInform Abstract: Rhodium‐Catalyzed Synthesis of Amides from Aldehydes and Azides by Chelation‐Assisted C—H Bond Activation.
Authors: Zhou Bing , Yang Yaxi , Shi Jingjing , Feng Huijin , Li Yuanchao 
Published: December 2013

AbstractThe first Rh(III)‐catalyzed direct amidation of aldehydes with sulfonyl, aryl, and alkyl azides under free conditions without the use of any additive is presented.
ChemInform Abstract: Povarov‐Reductive Amination Cascade to Access 6‐Aminoquinolines and Anthrazolines.
Authors: Pericherla Kasiviswanadharaju , Kumar Anil , Jha Amitabh 
Published: December 2013

AbstractA new strategy is reported to synthesize the title compounds via a tandem Povarov reaction, dihydroquinoline oxidation, and imine reduction.