bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of systemic morpholino exon‐skipping in duchenne dystrophy dogs
Authors: Yokota Toshifumi , Lu Qi‐long , Partridge Terence , Kobayashi Masanori , Nakamura Akinori , Takeda Shińichi , Hoffman Eric 
Published: March 2009

AbstractObjectiveDuchenne muscular dystrophy (DMD) is caused by the inability to produce dystrophin protein at the myofiber membrane. A method to rescue dystrophin production by antisense oligonucleotides, termed exon‐skipping, has been reported for the mdx mouse and in four DMD patients by local intramuscular injection. We sought to test efficacy and toxicity of intravenous oligonucleotide (morpholino)‐induced exon skipping in the DMD dog model.MethodsWe tested a series of antisense drugs singly and as cocktails, both in primary cell culture, and two in vivo delivery methods (intramuscular injection and systemic intravenous injection). The efficiency and efficacy of multiexon skipping (exons 6–9) were tested at the messenger RNA, protein, histological, and clinical levels.ResultsWeekly or biweekly systemic intravenous injections with a three‐morpholino cocktail over the course of 5 to 22 weeks induced therapeutic levels of dystrophin expression throughout the body, with an average of about 26% normal levels. This was accompanied by reduced inflammatory signals examined by magnetic resonance imaging and histology, improved or stabilized timed running tests, and clinical symptoms. Blood tests indicated no evidence of toxicity.InterpretationThis is the first report of widespread rescue of dystrophin expression to therapeutic levels in the dog model of DMD. This study also provides a proof of concept for systemic multiexon‐skipping therapy. Use of cocktails of morpholino, as shown here, allows broader application of this approach to a greater proportion of DMD patients (90%) and also offers the prospect of selecting deletions that optimize the functionality of the dystrophin protein. Ann Neurol 2009
Supramolecular ABC Triblock Copolymers
Authors: Ambade Ashootosh V. , Yang Si Kyung , Weck Marcus 
Published: March 2009

AbstractNur rein damit! Rutheniuminitiatoren mit Bindungsstellen für Wasserstoffbrücken lösen eine Ringöffnungsmetathesepolymerisation aus, die in einer Stufe heterotelechele Polymere mit Wasserstoffbrücken‐ und Metallkoordinationsstellen ergibt. Supramolekulare ABC‐Triblockcopolymere wurden anschließend direkt durch Zugabe komplementärer telecheler Polymere zu Lösungen der heterotelechelen Polymere erhalten (siehe Bild).magnified image
Incorporation of Fe3O4 Nanoparticles into Organometallic Coordination Polymers by Nanoparticle Surface Modification
Authors: Kim Sang Bok , Cai Chen , Sun Shouheng , Sweigart Dwight A. 
Published: March 2009

AbstractOberflächenmodifizierte Fe3O4‐Nanopartikel (NPs) werden durch den Austausch von Oleylamin‐Schutzgruppen gegen [(η5‐Semichinon)Mn(CO)3]‐Einheiten erhalten. Sie können als Keim oder Templat bei der Bildung kristalliner Koordinationspolymere wirken, die die superparamagnetischen Fe3O4‐NPs dann einschließen. Hybride magnetische Eigenschaften resultieren, wenn paramagnetische Metallzentren wie Mn2+ in die Polymere eingeführt werden (siehe Bild).magnified image
Peptides Recognize Photoresponsive Targets
Authors: Chen Jing , Serizawa Takeshi , Komiyama Makoto 
Published: March 2009

AbstractNie auf dem falschen Film: 7‐mer‐Peptide, die an Azobenzol‐haltige Polymerfilme binden, wurden unter Einstrahlung von sichtbarem Licht aus einer Phagenbibliothek selektiert. Isolierte Klone hatten unter UV‐Bestrahlung höhere Affinitäten für die Filme als unter sichtbarem Licht. Die Bindung der Peptide reagiert auch auf die lichtinduzierte Isomerisierung der Azobenzoleinheiten.magnified image
Exploring the Limits of Förster Theory for Energy Transfer at a Separation of 20 Å
Authors: Ziessel Raymond , Alamiry Mohammed A. H. , Elliott Kristopher J. , Harriman Anthony 
Published: March 2009

AbstractFür Donor‐Spacer‐Akzeptor‐Systeme, die Bordipyrromethaneinheiten als Donor‐ und Akzeptorkomponente in verschiedenen Protonierungsstufen enthalten, wurde eine ausgezeichnete Übereinstimmung zwischen den experimentellen und berechneten Matrixelementen der Coulomb‐Kopplung erhalten. Das Vorliegen dieser Korrelation ist bemerkenswert, weil für intramolekulare Elektronentransfers über kurze Entfernungen (hier 20 Å) die Förster‐Theorie nur mit Einschränkungen gültig ist (siehe Bild).magnified image
Direct Alkenylation of Indoles with α‐Oxo Ketene Dithioacetals: Efficient Synthesis of Indole Alkaloids Meridianin Derivatives
Authors: Yu Haifeng , Yu Zhengkun 
Published: March 2009

AbstractDurch säurevermittelte Substitution von α‐Oxoketendithioacetalen mit Indolen in Trifluoressigsäure(TFA)/Dichlormethan gelingt die metallfreie direkte Alkenylierung von Indolen; man erhält selektiv α,β‐ungesättigte Carbonylverbindungen mit einem oder zwei Indolylsubstituenten in β‐Stellung (siehe Schema). Die Kondensation der Indolyl/Keten‐Monothioacetale mit Guanidiniumnitrat liefert effizient Meridianinderivate.magnified image
Meniscus deformation and dynamics of moving contact line between poly(ethylene terephthalate) surface and glycerol–water mixtures
Authors: Karakashev Stoyan I. , Nguyen Anh V. 
Published: March 2009

AbstractThe microscopic hydrodynamic (HD) and macroscopic theories for describing the meniscus deformation and dynamics of a moving contact line have been analyzed and compared by using the extrapolated dynamic contact angles between a poly(ethylene terephthalate) (PET) surface and glycerol–water mixtures. The analysis showed that the microscopic theory is confined by the microscopic length scale and small capillary number. The macroscopic theory is not subjected to any restrictions. Three (inner, intermediate and outer) regions of the dynamic meniscus have been combined by using the contact molecular kinetics and hydrodynamics. The combined molecular‐HD theory has been validated using the experimental data for the extrapolated dynamic contact angles between a PET surface and glycerol–water mixtures. The analysis showed that the combined theory describes the phenomenon of wetting qualitatively. It was found that the contradiction within the theoretical framework of the molecular kinetics and hydrodynamics hinders the exact description of the wetting phenomenon. Copyright © 2009 Curtin University of Technology and John Wiley & Sons, Ltd.
Faster clearance of omeprazole in mutant Nagase analbuminemic rats: possible roles of increased protein expression of hepatic CYP1A2 and lower plasma protein binding
Authors: Lee Dae Y. , Jung Young S. , Kim Young C. , Kim Sung Y. , Lee Myung G. 
Published: March 2009

AbstractIt is well known that there are various changes in the expression of hepatic and intestinal CYPs in mutant Nagase analbuminemic rats (NARs). It has been reported that the protein expression of hepatic CYP1A2 was increased, whereas that of hepatic CYP3A1 was not altered, and it was also found that the protein expression of the intestinal CYP1A subfamily significantly increased in NARs from our other study. In addition, in this study additional information about CYP changes in NARs was obtained; the protein expression of the hepatic CYP2D subfamily was not altered, but that of the intestinal CYP3A subfamily increased in NARs. Because omeprazole is metabolized via hepatic CYP1A1/2, 2D1, 3A1/2 in rats, it could be expected that the pharmacokinetics of omeprazole would be altered in NARs. After intravenous administration of omeprazole to NARs, theClnrwas significantly faster than in the controls (110 versus 46.6 ml/min/kg), and this could be due to an increase in hepatic metabolism caused by a greater hepatic CYP1A2 level in addition to greater free fractions of the drug in NARs. After oral administration of omeprazole to NARs, the AUC was also significantly smaller (80.1% decrease) andFwas decreased in NARs. This could be primarily due to increased hepatic and intestinal metabolism caused by greater hepatic CYP1A2 and intestinal CYP1A and 3A levels. In particular, the smallerFcould mainly result from greater hepatic and intestinal first‐pass effect in NARs than in the controls. Copyright © 2009 John Wiley & Sons, Ltd.
An electronic device for accelerating bone formation in tissues surrounding a dental implant
Authors: Song Jong K. , Cho Tae H. , Pan Hui , Song Yoon M. , Kim In S. , Lee Tae H. , Hwang Soon J. , Kim Sung J. 
Published: March 2009

AbstractA dental implant is a unique structure which can be used with a noninvasive method because it is inserted into the bone in part and extended extracorporally. This study presents an electronic device that is temporarily connected with the dental implant, and reports its effect on accelerating bone formation in the surrounding tissues in a canine mandibular model. A small sized and low power consumption biphasic electrical current (BEC) stimulator ASIC was developed and the surrounding tissue was exposed to continuous BEC stimulation for 7 days with the parameters of 20 µA/cm2, 125 µs duration, and 100 pulses/s. After 2 (n = 5) and 5 weeks (n = 5), animals were sacrificed and the specimens were histomorphometrically evaluated. The newly formed bone area (BA) was 1.30 times (3 weeks, P < 0.05) and 1.35 times (5 weeks, P < 0.05) higher in the experimental group compared to the control group, respectively. Bone‐implant contact (BIC) in 3‐week specimens was 1.62 times (P < 0.05) greater in the experimental group, while there was no statistically significant difference in 5‐week specimens. Based on these results showing accelerated bone formation on and around the dental implant, it could be suggested that the latent time for osseointegration in dental implants can be reduced, and the success rate of implants in poor quality bone can be increased by using our device with BEC. Bioelectromagnetics 30:374–384, 2009. © 2009 Wiley‐Liss, Inc.
Separation of product associating E. coli host cell proteins OppA and DppA from recombinant apolipoprotein A‐IMilano in an industrial HIC unit operation
Authors: Hunter Alan K. , Wang Xing , Suda Eric J. , Herberg John T. , Shell Robert E. , Thomas Kristin E. , Dufield Robert L. , Gustafson Mark E. , Mozier Ned M. , Ho Sa. V. 
Published: March 2009

AbstractWe have shown how product associating E. coli host cell proteins (HCPs) OppA and DppA can be substantially separated from apolipoprotein A‐IMilano (apo A‐IM) using Butyl Sepharose hydrophobic interaction chromatography (HIC). This work illustrates the complex problems that frequently arise during development and scale‐up of biopharmaceutical manufacturing processes. Product association of the HCPs is confirmed using co‐immunoprecipitation and Western blotting techniques. Two‐dimensional gel electrophoresis and mass spectrometry techniques are used to confirm the identity of OppA and DppA. In this example, clearance of these difficult to separate HCPs decreased significantly when the process was scaled to a 1.4 m diameter column. Laboratory‐scale experimentation and trouble shooting identified several key parameters that could be further optimized to improve HCP clearance. The key parameters included resin loading, peak cut point on the ascending side, wash volume, and wash salt concentration. By implementing all of the process improvements that were identified, it was possible to obtain adequate HCP clearance so as to meet the final specification. Although it remains speculative, it is believed that viscosity effects may have contributed to the lower HCP clearance observed early in the manufacturing campaign. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
A Tin–Tungsten Mixed Oxide as an Efficient Heterogeneous Catalyst for CC Bond‐Forming Reactions
Authors: Ogasawara Yoshiyuki , Uchida Sayaka , Yamaguchi Kazuya , Mizuno Noritaka 
Published: March 2009

AbstractMix and calcinate: The tin–tungsten mixed oxide (Sn–W oxide) prepared by calcination of the Sn–W hydroxide at 800 °C acts as an effective and reusable solid catalyst for CC bond‐forming reactions, such as the cyclization of citronellal, the Diels–Alder reaction, and the cyanosilylation of carbonyl compounds with trimethylsilyl cyanide (see scheme). The observed catalysis was truly heterogeneous, and the recovered catalyst could be reused without loss of its high catalytic performance.magnified imageThe tin–tungsten mixed oxide prepared by the calcination of the tin–tungsten hydroxide precursor with a Sn/W molar ratio of 2 at 800 °C (SnW2–800) acts as an effective and reusable solid catalyst for CC bond‐forming reactions, such as the cyclization of citronellal, the Diels–Alder reaction, and the cyanosilylation of carbonyl compounds with trimethylsilyl cyanide (TMSCN). Various kinds of structurally diverse aliphatic, aromatic, and unsaturated, heteroatom‐containing substrates could be converted into the desired products in high to excellent yields. The observed catalyses for these reactions were truly heterogeneous and the recovered catalyst could be reused several times without an appreciable loss of its high catalytic performance. The Brønsted acid sites generated on the aggregated polytungstate species on SnW2–800 likely play an important role in the CC bond‐forming reactions.
Non‐UV‐Induced Radical Reactions at the Surface of TiO2Nanoparticles That May Trigger Toxic Responses
Authors: Fenoglio Ivana , Greco Giovanna , Livraghi Stefano , Fubini Bice 
Published: March 2009

AbstractKept in the dark: The non‐photocatalytic generation of free radicals from fine and ultrafine TiO2particles has been studied by means of a spin‐trapping/ESR spectroscopy technique (see figure). The amount and kind of free radicals generated depends on the crystalline structure, but not on the particle dimensions.magnified imageTitania is generally considered to be an inert and safe material. Several studies, however, have reported that nanosized TiO2may elicit toxic effects. In some cases the observed adverse effects have been related to free radicals. Although new studies mainly concern irradiated titania, the role and the mechanisms of the generation of free radicals by TiO2in the absence of UV irradiation are not well known. The purpose of the present study is to investigate the free‐radical‐generation mechanisms by nano‐ and micronsized anatase or rutile powders under normal laboratory illumination or in the dark by means of a spin‐trapping/ESR spectroscopy technique. This technique is used to identify the nature and the amount of free radicals released in solution, and in the solid‐state to characterise the paramagnetic centres at the surface of particles that may participate in the reactions. The following radical‐generating mechanisms have been considered: 1) the generation of oxygenated free radicals (HO2., O2.−, HO.) following the reaction of TiO2with oxygen, water or H2O2and 2) the generation of carbon‐centred radicals following the cleavage of the CH bond in a model molecule. Although no free radicals were detected in a simply buffered solution, anatase and rutile generated O2.−and HO., respectively, in the presence of H2O2. Both polymorphs were also active in the cleavage of the CH bond. Although the formation of O2.−appears to be related to exposure to sunlight, the generation of HO.and carbon‐centred free radicals also occurs in the dark. When samples of equal surface area were tested, micron‐ and nanosized anatase was found to react in the same way indicating that a reduction in diameter does not generate new kinds of reactive sites. The data presented herein may have implications in the assessment of the health risk associated with the exposure to TiO2nanoparticles and in the ecotoxicological impact following their possible leakage into the environment.
Methane Activation by Metal‐Free Radical Cations: Experimental Insight into the Reaction Intermediate
Authors: de Petris Giulia , Troiani Anna , Rosi Marzio , Angelini Giancarlo , Ursini Ornella 
Published: March 2009

AbstractA precise jab to methane: The SO2.+ radical cation (see figure) effectively activates CH4 at room temperature through a [H3C.⋅⋅⋅HOSO+] methyl intermediate isolated in the gas phase by mass spectrometry. Methanol and ionized methyl hydrogen sulfoxylate, CH3OSOH.+, are formed by selective, direct attack of the incipient methyl radical at the O atom of the intermediate. The reaction shows radical and charge effects in the activation of methane by metal‐free radical cations.magnified image
Synthesis of Pyrimidines and Triazines in Ice: Implications for the Prebiotic Chemistry of Nucleobases
Authors: Menor‐Salván César , Ruiz‐Bermejo Dra. Marta , Guzmán Marcelo I. , Osuna‐Esteban Susana , Veintemillas‐Verdaguer Sabino 
Published: March 2009

AbstractFrom urea to nucleobases: Freeze–thaw cycles in urea (1) solutions under methane/nitrogen atmospheres lead, with application of an energy source, to the synthesis of pyrimidines (mainly cytosine (2) and uracil (3)), triazines (such as cyanuric acid (4)), and adenine. This synthesis appears to be dependent on the atmosphere and the freezing conditions. At room temperature, hydantoin (5) is obtained. However, a freezing urea/water system subjected to an energy source under an inert atmosphere generates s‐triazines.magnified imageHerein, we report the efficient synthesis of RNA bases and functionalized s‐triazines from 0.1 M urea solutions in water after subjection to freeze–thaw cycles for three weeks. The icy solution was under a reductive, methane‐based atmosphere, which was subjected to spark discharges as an energy source for the first 72 h of the experiment. Analysis of the products indicates the synthesis of the s‐triazines cyanuric acid, ammeline, ammelide, and melamine, the pyrimidines cytosine, uracil, and 2,4‐diaminopyrimidine, and the purine adenine. An experiment performed as a control at room temperature, with the urea solution in the liquid phase and with the same atmosphere and energy source, led to the synthesis of hydantoins and insoluble tholin, but there was no evidence of the synthesis of pyrimidines or triazines. The synthesis of pyrimidines from urea is possible under a methane/nitrogen atmosphere only at low temperature, in the solid phase. The generation of both pyrimidines and triazines in comparable yields from urea, together with a possible role for triazines as alternative nucleobases, opens new perspectives on the prebiotic chemistry of informational polymers.
Density Functional Theory Investigation of the Alkyl–Alkyl Negishi Cross‐Coupling Reaction Catalyzed by N‐Heterocyclic Carbene (NHC)–Pd Complexes
Authors: Chass Gregory A. , O'Brien Christopher J. , Hadei Niloufar , Kantchev Eric Assen B. , Mu Wei‐Hua , Fang De‐Cai , Hopkinson Alan C. , Csizmadia Imre G. , Organ Michael G. 
Published: March 2009

AbstractWhy bigger is better: A “steric wall” created by theN‐(2,6‐diisopropylphenyl) substituent on the bulky NHC ligand IPr (1,3‐bis(2,6‐diisopropylphenyl)imidazol‐2‐ylidene) guides the reactants to and from the Pd center through weak, fleeting (IPr)H–Pd interactions that help the oxidative addition intermediate escape “the anti‐trap”. The alternative “side” approach leads to transmetalation (the rate‐limiting step) for which a novel Pd–Zn interaction was identified.magnified imageA novel mechanism is proposed for the Pd–1,3‐(2,6‐diisopropylphenyl)imidazolyl‐2‐ylidene (1) catalyzed Negishi reaction. DFT computations supported by atoms‐in‐molecules (AIM) analyses of non‐truncated models show that a “steric wall” created by theN‐substituent on the ligand guides reactants to and from the Pd center. Notably, transmetalation and not oxidative addition is found to be rate‐limiting. Additionally, a key Pd–Zn interaction (≈2.4 Å,ρb≈0.0600 au) is identified in the mechanism. This interaction persists beyond reductive elimination and, in combination with the ligand, facilitates reductive elimination by creating a highly sterically crowded environment in the coordination sphere of the Pd center.
A Very Efficient Cerium(IV) Ammonium Nitrate Catalyzed, Four‐Component Synthesis of Tetrahydropyridines and Its Application in the Concise Generation of Functionalized Homoquinolizine Frameworks
Authors: Sridharan Vellaisamy , Maiti Swarupananda , Menéndez J. Carlos 
Published: March 2009

AbstractMolecular diversity: A cerium(IV) ammonium nitrate (CAN) catalyzed, four‐component reaction from very simple acyclic starting materials afforded densely substituted tetrahydropyridines, which were transformed into homoquinolizines by using a γ‐alkylation–ring‐closing metathesis (RCM) sequence (see scheme).magnified imageThe cerium(IV) ammonium nitrate (CAN) catalyzed, four‐component reaction between primary aliphatic amines, β‐ketoesters or β‐ketothioesters, α,β‐unsaturated aldehydes, and alcohols provided a very efficient and atom‐economical access to substituted 6‐alkoxy‐2‐methyl‐1,4,5,6‐tetrahydropyridines. These materials were then transformed into homoquinolizine derivatives in excellent yields by using a two‐step sequence comprised of regioselective γ‐deprotonation–allylation and ring‐closing metathesis reactions. The possibility of displacing the alkoxy group by allylsilane nucleophiles, presumably through a vinylogous acyliminium intermediate species, was also demonstrated.
Structure‐Based Optimization of Benzoic Acids as Inhibitors of Protein Tyrosine Phosphatase 1B and Low Molecular Weight Protein Tyrosine Phosphatase
Authors: Maccari Rosanna , Ottanà Rosaria , Ciurleo Rosella , Paoli Paolo , Manao Giampaolo , Camici Guido , Laggner Christian , Langer Thierry 
Published: March 2009

AbstractWe have optimized previously discovered benzoic acids 1, which are active as inhibitors of PTP1B and LMW‐PTP, two protein tyrosine phosphatases that have emerged as attractive targets for the development of novel therapeutic agents for the treatment of diabetes, obesity, and cancer. Our efforts led to the identification of new and more potent analogues with appreciable selectivity toward human PTP1B and the IF1 isoform of human LMW‐PTP.magnified image
The Ever‐Elusive Tetra‐tert‐butylethene (TTBE, 3,4‐Di‐tert‐butyl‐ 2,2,5,5‐tetramethylhex‐3‐ene): Further Insight on Its Preparation
Authors: Klein Oliver , Hopf Henning , Grunenberg Jörg 
Published: March 2009

AbstractDiketone 4 was prepared by hydrolysis of hexendiyne 5, the latter being available through McMurry coupling of acetylenic ketone 26. Upon treatment with dimethyltitanium dichloride, 4 cyclizes into fully alkylated furan derivative 30; the still unknown tetra‐tert‐butylethene (1, TTBE, 3,4‐di‐tert‐butyl‐2,2,5,5‐tetramethylhex‐3‐ene) was not produced. The structural properties of 4 and the mechanism of its cyclization into 30 are discussed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)