bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular Modeling, Synthesis, and Biological Evaluation of Macrocyclic Calpain Inhibitors
Authors: Abell Andrew D. , Jones Matthew A. , Coxon James M. , Morton James D. , Aitken Steven G. , McNabb Stephen B. , Lee Hannah Y.‐Y. , Mehrtens Janna M. , Alexander Nathan A. , Stuart Blair G. , Neffe Axel T. , Bickerstaffe Roy 
Published: January 2009

AbstractEntwurf und Synthese einer Reihe von makrocyclischen Gerüsten, die eine β‐Strang‐ähnliche Peptidrückgrat‐Konformation bevorzugen, führten zu wirksamen und selektiven Inhibitoren von Calpain 2. Der Makrocyclus 1 verzögerte die calciuminduzierte Eintrübung von Schafslinsen in Kultur und dient als Leitstruktur für die Entwicklung eines Wirkstoffs zur Behandlung von grauem Star. Cbz=Carbobenzyloxy.magnified image
Selektive Fluoreszenzmarkierung von Lipiden in lebenden Zellen
Authors: Neef Anne B. , Schultz Carsten 
Published: January 2009

AbstractKlick‐Chemie für die Visualisierung von Lipiden in vivo: Drei Phosphatidsäurederivate mit Dreifachbindungen in den Fettsäureseitenketten wurden synthetisiert und in Säugerzellmembranen eingebaut. Für ihre Visualisierung wurden Kupfer(I)‐katalysierte sowie ringspannungsinduzierte Azid‐Alkin‐Cycloadditionen verwendet.magnified image
Tandem Double‐Michael‐Addition/Cyclization/Acyl Migration of 1,4‐Dien‐3‐ones and Ethyl Isocyanoacetate: Stereoselective Synthesis of Pyrrolizidines
Authors: Tan Jing , Xu Xianxiu , Zhang Lingjuan , Li Yifei , Liu Qun 
Published: January 2009

AbstractBis zu vier benachbarte Stereozentren können stereoselektiv beim Aufbau eines Pyrrolizidinsystems eingeführt werden, indem man Dienone in einer neuartigen DBU‐katalysierten organokatalytischen Reaktion mit Ethylisocyanacetat umsetzt (siehe Schema; DBU=1,8‐Diazabicyclo[5.4.0]undec‐7‐en). Ein Mechanismus für dieses atomökonomische Eintopfverfahren wird vorgeschlagen.magnified image
Formate as a Surface Probe for Ruthenium Nanoparticles in Solution 13C NMR Spectroscopy
Authors: Tedsree Karaked , Kong Adam T. S. , Tsang Shik Chi 
Published: January 2009

AbstractFormic acid adsorption on ruthenium nanoparticles of different sizes allows differentiation of differently bound formate species by solution 13C NMR spectroscopy (see picture). The chemical shifts are comparable to those of organometallic analogues, thus indicating that formate can act as a probe to distinguish surface features of metallic nanoparticles in solution with good quantification and resolution.magnified image
The Norbornene Shuttle: Multicomponent Domino Synthesis of Tetrasubstituted Helical Alkenes through Multiple CH Functionalization
Authors: Gericke Kersten M. , Chai David I. , Bieler Nikolas , Lautens Mark 
Published: January 2009

AbstractShall we dance? Within the proposed mechanism for the palladium‐catalyzed title reaction, the strained alkene norbornene (or norbornadiene) enters and exits the catalytic cycle in a catalytic “square dance”, acting as both a promoter and a coupling partner in the formation of four carbon–carbon bonds, two of them by challenging CH activation processes.magnified image
Perfluoropentaphenylborole
Authors: Fan Cheng , Piers Warren E. , Parvez Masood 
Published: January 2009

AbstractPerfluorination: The fully fluorinated analogue of pentaphenylborole (see structure; B gray, C black, F green) has been prepared using successive transmetallation reactions involving Zr and Sn heterocycles. The highly moisture‐sensitive borole is a new member of the perfluoroaryl borane family, a class of antiaromatic compounds of fundamental significance to concepts of aromaticity.magnified image
Increasing the Antigenicity of Synthetic Tumor‐Associated Carbohydrate Antigens by Targeting Toll‐Like Receptors
Authors: Ingale Sampat , Wolfert Margreet A. , Buskas Therese , Boons Geert‐Jan 
Published: January 2009

AbstractSynthetic cancer vaccines: A number of fully synthetic vaccine candidates have been designed, chemically synthesized, and immunologically evaluated to establish a strategy to overcome the poor immunogenicity of tumor‐associated carbohydrates and glycopeptides and to determine the importance of Toll‐like receptor (TLR) engagement for antigenic responses against these compounds.magnified imageEpithelial cancer cells often overexpress mucins that are aberrantly glycosylated. Although it has been realized that these compounds offer exciting opportunities for the development of immunotherapy for cancer, their use is hampered by the low antigenicity of classical immunogens composed of a glycopeptide derived from a mucin conjugated to a foreign carrier protein. We have designed, chemically synthesized, and immunologically evaluated a number of fully synthetic vaccine candidates to establish a strategy to overcome the poor immunogenicity of tumor‐associated carbohydrates and glycopeptides. The compounds were also designed to allow study of the importance of Toll‐like receptor (TLR) engagement for these antigenic responses in detail. We have found that covalent attachment of a TLR2 agonist, a promiscuous peptide T‐helper epitope, and a tumor‐associated glycopeptide gives a compound (1) that elicits in mice exceptionally high titers of IgG antibodies that recognize MCF7 cancer cells expressing the tumor‐associated carbohydrate. Immunizations with glycolipopeptide 2, which contains lipidated amino acids instead of a TLR2 ligand, gave significantly lower titers of IgG antibodies; this demonstrates that TLR engagement is critical for optimum antigenic responses. Although mixtures of compound 2 with Pam3CysSK4 (3) or monophosphoryl lipid A (4) elicited titers of IgG antibodies similar to those seen with 1, the resulting antisera had impaired ability to recognize cancer cells. It was also found that covalent linkage of the helper T‐epitope to the B‐epitope is essential, probably because internalization of the helper T‐epitope by B‐cells requires assistance of the B‐epitope. The results presented here show that synthetic vaccine development is amenable to structure–activity relationship studies for successful optimization of carbohydrate‐based cancer vaccines.
1H{19F} NOE NMR Structural Signatures of the Insulin R6Hexamer: Evidence of a Capped HisB10 Site in Aryl‐ and Arylacryloyl‐carboxylate Complexes
Authors: Keidel Donald , Bonaccio Maria , Ghaderi Nima , Niks Dimitri , Borchardt Dan , Dunn Michael F. 
Published: January 2009

AbstractNew and improved insulin:1H{19F} NOE NMR difference spectra for CF3‐substituted aromatic carboxylates bound at the HisB10 sites of the R6human insulin (HI) hexamer show strong NOEs between the CF3groups and the LeuB6, AsnB3, and PheB1 sidechains. The NOEs and structural modeling establish that these carboxylates form closed complexes with the HisB10 site capped by the PheB1 rings.magnified image
Design, Synthesis, and Biological Evaluation of Enantiomeric β‐N‐Acetylhexosaminidase Inhibitors LABNAc and DABNAc as Potential Agents against Tay‐Sachs and Sandhoff Disease
Authors: Rountree J. S. Shane , Butters Terry D. , Wormald Mark R. , Boomkamp Stephanie D. , Dwek Raymond A. , Asano Naoki , Ikeda Kyoko , Evinson Emma L. , Nash Robert J. , Fleet George W. J. 
Published: January 2009

AbstractCombating glycolipid storage disorders: LABNAc was prepared in an efficient 11‐step procedure from D‐lyxonolactone. The enantiomer DABNAc was also prepared from L‐lyxonolactone. Preliminary cellular studies indicate that these compounds may find utility as chemical chaperones for the treatment of Tay‐Sachs and Sandhoff diseases.magnified imageN‐Acetylhexosaminidases are of considerable importance in mammals and are involved in various significant biological processes. In humans, deficiencies of these enzymes in the lysosome, resulting from inherited genetic defects, cause the glycolipid storage disorders Tay‐Sachs and Sandhoff diseases. One promising therapy for these diseases involves the use of β‐N‐acetylhexosaminidase inhibitors as chemical chaperones to enhance the enzyme activity above sub‐critical levels. Herein we describe the synthesis and biological evaluation of a potent inhibitor, 2‐acetamido‐1,4‐imino‐1,2,4‐trideoxy‐L‐arabinitol (LABNAc), in a high‐yielding 11‐step procedure from D‐lyxonolactone. The N‐benzyl and N‐butyl analogues were also prepared and found to be potent inhibitors. The enantiomers DABNAc and NBn‐DABNAc were synthesised from L‐lyxonolactone, and were also evaluated. The L‐iminosugar LABNAc and its derivatives were found to be potent noncompetitive inhibitors of some β‐N‐acetylhexosaminidases, while the D‐iminosugar DABNAc and its derivatives were found to be weaker competitive inhibitors. These results support previous work postulating that D‐iminosugar mimics inhibit D‐glycohydrolases competitively, and that their corresponding L‐enantiomers show noncompetitive inhibition of these enzymes. Molecular modelling studies confirm that the spatial organisation in enantiomeric inhibitors leads to a different overlay with the monosaccharide substrate. Initial cell‐based studies suggest that NBn‐LABNAc can act as a chemical chaperone to enhance the deficient enzyme's activity to levels that may cause a positive pharmacological effect. LABNAc, NBn‐LABNAc, and NBu‐LABNAc are potent and selective inhibitors of β‐N‐acetylhexosaminidase and may be useful as therapeutic agents for treating adult Tay‐Sachs and Sandhoff diseases.
Early lead exposure effects on an auditory threshold task in the rhesus monkey (Macaca mulatta)
Authors: Laughlin Nellie K. , Luck Melissa L. , Lasky Robert E. 
Published: January 2009

AbstractBehavioral thresholds to pure tones were obtained from adult rhesus monkeys that had been exposed to lead during early development and unexposed cohort controls. Thresholds were elevated (by 2–9 dB) for the previously lead exposed monkeys at all frequencies tested (125–8,000 Hz in octave steps). Although the magnitude and direction of the differences were similar to significant effects reported for children, the more difficult task and much smaller sample sizes in this study of monkeys may have precluded obtaining significant differences at the same magnitude of effects observed in children. Thresholds for one lead‐exposed monkey were significantly elevated at midrange frequencies in agreement with electrophysiological results obtained in another study [Lasky, Maier, Snodgrass, Hecox, and Laughlin [1995] Neurotoxicology and Teratology, 17, 633–644]. Behavioral measurements during the threshold task indicated less engagement for lead exposed monkeys than for controls. In addition, the lead exposed monkeys completed testing at significantly fewer frequencies and were significantly more difficult to test than control monkeys by tester ratings. These results are consistent with reports concerning the behavior of lead exposed children. © 2009 Wiley Periodicals, Inc. Dev Psychobiol 51: 289–300, 2009
Insulin analogues display IGF‐I‐like mitogenic and anti‐apoptotic activities in cultured cancer cells
Authors: Weinstein Doron , Simon Meital , Yehezkel Einat , Laron Zvi , Werner Haim 
Published: January 2009

AbstractBackgroundInsulin analogues are widely used in the treatment of diabetes mellitus. Some insulin analogues were reported to display atypical activities in vitro that resemble those of insulin‐like growth factor‐I (IGF‐I). The aim of this study was to investigate whether two long‐acting insulin analogues [glargine (Lantus, Sanofi Aventis, Germany) and detemir (Levemir, Novo Nordisk, Denmark)] and two short‐acting analogues [lispro (Humalog, Eli Lilly, Indianapolis, USA) and aspart (Novolog, Novo Nordisk, Denmark)] exhibit IGF‐I‐like activities on cultured cancer cells in comparison with IGF‐I and regular human insulin.MethodsHCT‐116 (colorectal cancer), PC‐3 (prostate cancer) and MCF‐7 (breast adenocarcinoma) cell lines were treated with insulin, IGF‐I or insulin analogues, and proliferation and protection from apoptosis were measured by cell counting and fluorescent‐activated cell sorter (FACS) analysis, respectively. In addition, Western blots were used to identify signalling molecules activated by the analogues.ResultsGlargine, detemir and lispro had proliferative effects that resemble IGF‐I action. Insulin, however, did not stimulate cellular proliferation. In addition, glargine and detemir displayed an IGF‐I‐like anti‐apoptotic activity. Glargine, like insulin and IGF‐I, induced phosphorylation of both ERK and AKT, suggesting that the analogue is able to stimulate both the ras‐raf‐mitogen‐activated protein kinase (MAPK) and PI3K‐AKT pathways. Furthermore, glargine induced both insulin receptor (IR) and IGF‐IR phosphorylation.ConclusionsGlargine, detemir and lispro, unlike regular insulin, exhibit in vitro proliferative and anti‐apoptotic activities in a number of cancer cell lines. These actions resemble some of the effects of IGF‐I, a growth factor involved in cancer initiation and progression. Insulin had no increased IGF‐I activity. The specific receptor/s involved in mediating analogues actions remains to be identified. Copyright © 2009 John Wiley & Sons, Ltd.
Harmonic characteristics of SC coil configuration for EDS maglev to reduce leakage flux
Authors: Murai Toshiaki , Sakamoto Yasuaki , Fujiwara Shunsuke , Yoshioka Hiroshi 
Published: January 2009

AbstractAn improved configuration of SC coils, whose end coils are small, is studied to reduce their leakage flux. This paper examines the harmonic characteristics when the improved configuration of SC coils is applied to the 120‐degree coil pitch ground coil. An adequate combination of length and mmf in the end coils can provide proper performance of harmonics and basis. © 2009 Wiley Periodicals, Inc. Electron Comm Jpn, 91(10): 20– 27, 2008; Published online in Wiley InterScience (www.interscience. wiley.com). DOI 10.1002/ecj.10163
A study of lightning phenomena on distribution lines based on a lightning‐surge analysis model for direct lightning strokes
Authors: Miyazaki Teru , Okabe Shigemitsu , Aiba Kiyoshi , Hirai Takao , Yoshinaga Jun 
Published: January 2009

AbstractIn order to rationalize the lightning protection design of distribution lines, lightning phenomena on TEPCO's distribution lines were continuously observed. The observations were carried out with still cameras and lightning surge monitoring sensors. The results elucidate the lightning performance of distribution lines. For example, direct lightning strokes are the major cause of the present distribution line faults. This fact suggests that it is important to investigate observation data on direct lightning strokes. The observation data were analyzed by means of a direct lightning analysis model. The calculated waveforms were compared with the measured waveforms on distribution lines. The probability distributions of the surge currents and voltages were calculated by the Monte Carlo method. These results provide new data on lightning performance. © 2009 Wiley Periodicals, Inc. Electron Comm Jpn, 91(10): 28– 37, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecj.10164
Heterometallic Ferrocene‐Rhenium Complexes Linked by an Aminoethylglycine Scaffold
Authors: Levine Lauren A. , Kirin Srećko I. , Myers Carl P. , Showalter Scott A. , Williams Mary Elizabeth 
Published: January 2009

AbstractUsing mono‐ and 1,n′‐disubstituted ferrocenecarboxylic acid, the aminoethylglycine (aeg) derivatives Fe[C5H4‐CO‐aeg‐OtBu][C5H5] (1) and Fe[C5H4‐CO‐aeg‐OtBu]2 (2) have been synthesized. Complexes 1 and 2 are further reacted to substitute the aeg with the nitrogen‐containing ligands dpa‐ph‐CO2H or py‐AcOH to yield complexes 3–6. Each of these is treated with Re(CO)5Cl to assemble heterometallic structures 3Re–6Re. These are subsequently isolated and characterized by NMR and mass spectrometry, FTIR, UV/Vis absorbance, and fluorescence emission spectroscopy, and separately by electrochemistry. All of the compounds exhibit the characteristic redox properties of the ferrocene moiety; in the heterometallic compounds, an irreversible oxidative wave is attributed to the Re. The electrochemically determined diffusion coefficients of the compounds confirm that the as‐prepared structures are discrete assemblies and not coordination polymers.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Ammonia‐Assisted Fabrication of Flowery Nanostructures of Metallic Nickel Assembled from Hexagonal Platelets
Authors: Ni Xiaomin , Zheng Huagui , Yang Qing , Tang Kaibin , Liao Guangxuan 
Published: January 2009

AbstractA simple one‐pot solution method was reported for the synthesis of metallic nickel nanostructures assembled from hexagonal nanoplatelets. The process involved the reduction of nickelous salt with hydrazine in ammonia solution, and the reaction proceeded without the use of surfactants or external magnetic forces. By properly adjusting the experimental parameters, we realized the anisotropic growth of face‐centered‐cubic (fcc) nickel into hexagonal nanoplatelets and their simultaneous assembly into flowery architectures. The cooperative effects of the ammonia complexing agent, a proper reaction rate, inherent magnetic interactions, and assembly entropy were considered the key factors driving the formation of the special assembly nanostructures on the basis of a series of contrast experiments. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Synthesis of Analogues of Acyclic Nucleoside Diphosphates Containing a (Phosphonomethyl)phosphanyl Moiety and Studies of Their Phosphorylation
Authors: Doláková Petra , Dračínský Martin , Fanfrlík Jindřich , Holý Antonín 
Published: January 2009

AbstractAcyclic nucleoside diphosphonate derivatives of purines and pyrimidines were prepared by Mitsunobu reaction of suitably protected heterocyclic bases with alcohols containing the (phosphonomethyl)phosphanyl moiety. Furthermore, nonhydrolyzable acyclic analogues of dUDP were prepared as potential inhibitors of dUTPase. Their phosphorylation to analogues of dUTP, however, gave mixtures of linear and branched phosphates. The courses of the phosphorylation reactions were followed by 31P NMR spectroscopy, and we discovered that both phosphonate and phosphinate moieties react with 1,1′‐carbonyldiimidazole and tri‐n‐butylammonium phosphate. The pKa values of the (phosphonomethyl)phosphanyl system were also determined by 31P NMR spectroscopy (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
A Bis(m‐phenylene)‐32‐crown‐10/Paraquat [2]Rotaxane
Authors: Li Shijun , Zhu Kelong , Zheng Bo , Wen Xianhong , Li Ning , Huang Feihe 
Published: January 2009

AbstractThe successful preparation of the first bis(m‐phenylene)‐32‐crown‐10/paraquat [2]rotaxane showed unambiguously that psuedorotaxane‐type complexation, rather than the taco‐complex‐type complexation previously observed in the solid state and in solution, exists – in solution – for complexation between bis(m‐phenylene)‐32‐crown‐10 derivatives and paraquat derivatives.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Relationship between Hpt polymorphisms and serum protein electropherogram
Authors: Guerranti Roberto , Bertocci Erica , Muzzi Chiara , Leoncini Roberto , Rossi Stefania , Scapellato Carlo , Pagani Roberto 
Published: January 2009

AbstractSerum protein electrophoresis is routinely used to identify pathologies involving dysproteinemia. The electropherogram mainly represents the most abundant serum proteins, one of which is the polymorphic haptoglobin (Hpt), characterized by a molecular heterogeneity with three major phenotypes (Hpt 1–1, 2–1, and 2–2). To improve the interpretation of electropherogram and possibly to extend its applicability, we aimed to explore the relationship between Hpt phenotypes (determined by immunoblotting) and protein profiles. Serum samples were separated by CZE with PROTEIN 6 and high‐resolution methods. The PROTEIN 6 analysis showed significant associations between α2 zone profiles and Hpt phenotypes (chi‐square=154.06, p<0.0001). The high‐resolution method indicated significant differences between Hpt 2–2 and Hpt 1–1 peak mobilities, evidenced by receiver operating characteristic analysis, (area under the receiver operating characteristic curve=0.98, p<0.0001, standard error=0.01346, likelihood ratios=21.39), with 98.7% sensitivity, and 95.4% specificity. However, the structural heterogeneity of Hpt 2–1 made it difficult to relate with a particular profile. Thus, we developed an alternative approach that excluded the Hpt 1–1 or Hpt 2–2 phenotypes. This may prove to be a useful technique in clinical applications considering the involvement of Hpt 2–2 or Hpt 1–1 in various pathologies.
Predictors of rapid cognitive decline among demented subjects aged 75 or more: (‘Sujet Agé Fragile—Evaluation et Suivi’ Cohort—SAFES)
Authors: Viatonou Saturnin , Dramé Moustapha , Jolly Damien , Morrone Isabella , Lang Pierre‐Olivier , Voisin Thierry , Boyer François Constant , Schwebel Gautier , Somme Dominique , Blanchard François , Novella Jean‐Luc 
Published: January 2009

AbstractObjectiveTo identify factors predictive of rapid cognitive decline (RCD) among elderly subjects aged 75 or over suffering from dementia.MethodsThe analysis concerned 250 patients drawn from the ‘Sujet Agé Fragile – Evaluation et Suivi’ (SAFES) cohort, presenting a dementia syndrome at inclusion and followed‐up for at least 1 year. RCD was defined as the loss of at least 3 points on the Mini‐Mental State Examination (MMSE) in the follow‐up period of 12 months. All patients underwent a standardised geriatric evaluation. Logistic regression was used to identify factors predictive of RCD.ResultsIn the study sample, 84 patients (33.6%) presented RCD. The factors identified in multivariate analysis as predictive of RCD were: high level of education (OR = 7.8, 95% CI = [1.9–31.2], p = 0.004), risk of depression (OR = 1.8, 95% CI = [1.02–3.18], p = 0.048, and the initial MMSE score (OR = 1.1, 95% CI = [1.0–1.2], p = 0.002). Among subjects with a main caregiver (n = 177), the predictive factors were malnutrition or risk thereof (OR = 4.2, 95% CI = [1.3–14.1], p = 0.02), risk of a fall (OR = 2.6, 95% CI = [1.1–6.1], p = 0.03, caregiver burden (OR = 2.6, 95% CI = [1.1–6.4], p = 0.04) and initial MMSE score (OR = 1.1, 95% CI = [1.0–1.3], p = 0.004).ConclusionsAs soon as dementia is diagnosed in elderly subjects, information should be collected about the subject's socioeconomic status, nutritional status, risk of falling, mood state, and caregiver burden. This would enable the provision of appropriate therapeutic care, and make it possible to adapt follow‐up in case of a risk of accelerated cognitive deterioration. Copyright © 2009 John Wiley & Sons, Ltd.