bluuebunny/crossref_metadata_2025 huggingface dataset:
Spelling and script debates in interwar Greece
Authors: Bernal Josep M.
Published: August 2007

The aim of this article is to explore the debates about the phonetic simplification of Greek orthography and the adoption of the Latin script that took place in Greece during the interwar period. An attempt will be made to examine the ideological background of these debates by placing them in their social and political context. First, the linguistic situation of Greece in the interwar years will be outlined. Then it will be argued that spelling and script issues were used as a battleground for the political and educational controversies of this period.
Nikos Gatsos’ Amorgos, topography and the poetics of modernism
Authors: Rentzou Effie
Published: August 2007

Nikos Gatsos’ Amorgos is approached here as a polyphonic poem that synthesizes elements of the Greek literary tradition into an intertextual palimpsest of fragments, in the vein of the modernist ‘long poem’. The surrealist poet maintains a fine balance between tradition and radical innovation, shaping Amorgos as a place where poetry is created as an interaction of opposing tendencies. The topical character of the poem is underscored by its title: the sea-and-land imagery evokes the island as a literary topos of seclusion and self-sufficiency that lends its characteristics to the composition itself: a ‘compendium’ of poetic writing and avant-garde aesthetics.
‘Poverty, prostitution, filthy tavernas’: cinephilia and popular Greek film of the fifties
Authors: Potamitis N. Y.
Published: August 2007

The diametrically opposed critical and commercial reception of two Greek films from the early 1950s exposes the contradictions inherent in the project of national cinema formation articulated by Greece’s cinephile press. Critics such as Eleni Vlachou and Marios Ploritis sought to locate Greek film within the context of a realist–humanist European art cinema, and denigrated the commercial cinema for its over-reliance on foreign models and popular genres. This cinephile discourse reveals, however, keenly felt anxieties of cultural authority and status, anxieties manifest in the constant shifting between the twin semantic poles of cultural indigeneity and foreign cinematic influence.
Down-regulation of the TGF-beta target gene, PTPRK, by the Epstein-Barr virus–encoded EBNA1 contributes to the growth and survival of Hodgkin lymphoma cells
Authors: Flavell Joanne R. , Baumforth Karl R. N. , Wood Victoria H. J. , Davies Gillian L. , Wei Wenbin , Reynolds Gary M. , Morgan Susan , Boyce Andrew , Kelly Gemma L. , Young Lawrence S. , Murray Paul G.
Published: August 2007

The Epstein-Barr virus (EBV) contributes to the growth and survival of Hodgkin lymphoma (HL) cells. Here we report that down-regulation of the transforming growth factor-beta (TGF-beta) target gene, protein tyrosine phosphatase receptor kappa (PTPRK), followed EBV infection of HL cells and was also more frequently observed in the Hodgkin and Reed-Sternberg (HRS) cells of EBV-positive compared with EBV-negative primary HL. The viability and proliferation of EBV-positive HL cells was decreased by overexpression of PTPRK, but increased following the knockdown of PTPRK expression in EBV-negative HL cells, demonstrating that PTPRK is a functional tumor suppressor in HL. EBV suppressed the TGF-beta–mediated activation of PTPRK expression, suggesting disruption of TGF-beta signaling upstream of PTPRK. This was confirmed when we showed that the Epstein-Barr nuclear antigen-1 (EBNA1) decreased Smad2 protein levels and that this was responsible for PTPRK down-regulation. EBNA1 decreased the half-life of Smad2 but did not interact with Smad2. By down-regulating Smad2 protein expression, EBNA1 apparently disables TGF-beta signaling, which subsequently decreases transcription of the PTPRK tumor suppressor. We speculate that loss of the phosphatase function of PTPRK may activate as-yet-unidentified growth-promoting protein tyrosine kinases, which in turn contribute to the pathogenesis of EBV-positive HL.
Submicroscopic bone marrow involvement in isolated extramedullary relapses in childhood acute lymphoblastic leukemia: a more precise definition of “isolated” and its possible clinical implications, a collaborative study of the Resistant Disease Committee of the International BFM study group
Authors: Hagedorn Nikola , Acquaviva Cécile , Fronkova Eva , von Stackelberg Arend , Barth Andrea , zur Stadt Udo , Schrauder André , Trka Jan , Gaspar Nathalie , Seeger Karl , Henze Günter , Cavé Hélène , Eckert Cornelia
Published: August 2007

This study investigates the extent of bone marrow (BM) involvement at diagnosis of apparent isolated extramedullary (AIEM) relapses of childhood acute lymphoblastic leukemia (ALL) and its relation to prognosis. Sixty-four children with first AIEM relapse treated in Germany, Czech Republic, or France were included. Real-time quantitative polymerase chain reaction using T-cell receptor and immunoglobulin gene rearrangements provided a sensitive measure of submicroscopic BM involvement, which was detectable at a level of 10−4 or higher in 46 patients and less than 10−4 in 11 patients, and was nondetectable (sensitivity: 10−4) in 7 patients. In the total cohort, the probability of event-free survival (pEFS) for children with BM involvement of 10−4 or higher was 0.30 (0.09 ± SE) versus 0.60 (± 0.12) for those with less than 10−4 (P = .13). The cumulative incidence of subsequent relapse was 0.24 (± 0.01) for patients with BM involvement less than 10−4 and 0.65 (± 0.01) for those with 10−4 or higher (P = .012). Restricted to central nervous system (CNS) relapses, pEFS was 0.11 (± 0.09) for patients with BM involvement 10−4 or higher and 0.63 (± 0.17) for those with less than 10−4 (P = .053). CNS relapses were associated with a higher (≥ 10−4: 80%) submicroscopic BM involvement than testicular relapses (≥ 10−4: 57%, P = .08). In summary, we show marked heterogeneity of submicroscopic BM involvement at first AIEM relapse diagnosis in children with ALL, and demonstrate its possible prognostic relevance.
Proapoptotic BH3-only protein Bim is essential for developmentally programmed death of germinal center-derived memory B cells and antibody-forming cells
Authors: Fischer Silke F. , Bouillet Philippe , O'Donnell Kristy , Light Amanda , Tarlinton David M. , Strasser Andreas
Published: August 2007

T cell–dependent B-cell immune responses induce germinal centers that are sites for expansion, diversification, and selection of antigen-specific B cells. During the immune response, antigen-specific B cells are removed in a process that favors the retention of cells with improved affinity for antigen, a cell death process inhibited by excess Bcl-2. In this study, we examined the role of the BH3-only protein Bim, an initiator of apoptosis in the Bcl-2–regulated pathway, in the programmed cell death accompanying an immune response. After immunization, Bim-deficient mice showed persistence of both memory B cells lacking affinity-enhancing mutations in their immunoglobulin genes and antibody-forming cells secreting low-affinity antibodies. This was accompanied by enhanced survival of both cell types in culture. We have identified for the first time the physiologic mechanisms for killing low-affinity antibody-expressing B cells in an immune response and have shown this to be dependent on the BH3-only protein Bim.
Chemical proteomic profiles of the BCR-ABL inhibitors imatinib, nilotinib, and dasatinib reveal novel kinase and nonkinase targets
Authors: Rix Uwe , Hantschel Oliver , Dürnberger Gerhard , Remsing Rix Lily L. , Planyavsky Melanie , Fernbach Nora V. , Kaupe Ines , Bennett Keiryn L. , Valent Peter , Colinge Jacques , Köcher Thomas , Superti-Furga Giulio
Published: August 2007

The BCR-ABL tyrosine kinase inhibitor imatinib represents the current frontline therapy in chronic myeloid leukemia. Because many patients develop imatinib resistance, 2 second-generation drugs, nilotinib and dasatinib, displaying increased potency against BCR-ABL were developed. To predict potential side effects and novel medical uses, we generated comprehensive drug-protein interaction profiles by chemical proteomics for all 3 drugs. Our studies yielded 4 major findings: (1) The interaction profiles of the 3 drugs displayed strong differences and only a small overlap covering the ABL kinases. (2) Dasatinib bound in excess of 30 Tyr and Ser/Thr kinases, including major regulators of the immune system, suggesting that dasatinib might have a particular impact on immune function. (3) Despite the high specificity of nilotinib, the receptor tyrosine kinase DDR1 was identified and validated as an additional major target. (4) The oxidoreductase NQO2 was bound and inhibited by imatinib and nilotinib at physiologically relevant drug concentrations, representing the first nonkinase target of these drugs.
Protective role of vascular endothelial growth factor in endotoxin-induced acute lung injury in mice
Authors: Koh Hidefumi , Tasaka Sadatomo , Hasegawa Naoki , Yamada Wakako , Shimizu Mie , Nakamura Morio , Yonemaru Makoto , Ikeda Eiji , Adachi Yoshiyuki , Fujishima Seitaro , Yamaguchi Kazuhiro , Ishizaka Akitoshi
Published: August 2007

Background

Vascular endothelial growth factor (VEGF), a substance that stimulates new blood vessel formation, is an important survival factor for endothelial cells. Although overexpressed VEGF in the lung induces pulmonary edema with increased lung vascular permeability, the role of VEGF in the development of acute lung injury remains to be determined.

Methods

To evaluate the role of VEGF in the pathogenesis of acute lung injury, we first evaluated the effects of exogenous VEGF and VEGF blockade using monoclonal antibody on LPS-induced lung injury in mice. Using the lung specimens, we performed TUNEL staining to detect apoptotic cells and immunostaining to evaluate the expression of apoptosis-associated molecules, including caspase-3, Bax, apoptosis inducing factor (AIF), and cytochrome C. As a parameter of endothelial permeability, we measured the albumin transferred across human pulmonary artery endothelial cell (HPAEC) monolayers cultured on porous filters with various concentrations of VEGF. The effect of VEGF on apoptosis HPAECs was also examined by TUNEL staining and active caspase-3 immunoassay.

Results

Exogenous VEGF significantly decreased LPS-induced extravascular albumin leakage and edema formation. Treatment with anti-VEGF antibody significantly enhanced lung edema formation and neutrophil emigration after intratracheal LPS administration, whereas extravascular albumin leakage was not significantly changed by VEGF blockade. In lung pathology, pretreatment with VEGF significantly decreased the numbers of TUNEL positive cells and those with positive immunostaining of the pro-apoptotic molecules examined. VEGF attenuated the increases in the permeability of the HPAEC monolayer and the apoptosis of HPAECs induced by TNF-α and LPS. In addition, VEGF significantly reduced the levels of TNF-α- and LPS-induced active caspase-3 in HPAEC lysates.

Conclusion

These results suggest that VEGF suppresses the apoptosis induced by inflammatory stimuli and functions as a protective factor against acute lung injury.
Setting up a large set of protein-ligand PDB complexes for the development and validation of knowledge-based docking algorithms
Authors: Diago Luis A , Morell Persy , Aguilera Longendri , Moreno Ernesto
Published: August 2007

Background

The number of algorithms available to predict ligand-protein interactions is large and ever-increasing. The number of test cases used to validate these methods is usually small and problem dependent. Recently, several databases have been released for further understanding of protein-ligand interactions, having the Protein Data Bank as backend support. Nevertheless, it appears to be difficult to test docking methods on a large variety of complexes. In this paper we report the development of a new database of protein-ligand complexes tailored for testing of docking algorithms.

Methods

Using a new definition of molecular contact, small ligands contained in the 2005 PDB edition were identified and processed. The database was enriched in molecular properties. In particular, an automated typing of ligand atoms was performed. A filtering procedure was applied to select a non-redundant dataset of complexes. Data mining was performed to obtain information on the frequencies of different types of atomic contacts. Docking simulations were run with the program DOCK.

Results

We compiled a large database of small ligand-protein complexes, enriched with different calculated properties, that currently contains more than 6000 non-redundant structures. As an example to demonstrate the value of the new database, we derived a new set of chemical matching rules to be used in the context of the program DOCK, based on contact frequencies between ligand atoms and points representing the protein surface, and proved their enhanced efficiency with respect to the default set of rules included in that program.

Conclusion

The new database constitutes a valuable resource for the development of knowledge-based docking algorithms and for testing docking programs on large sets of protein-ligand complexes. The new chemical matching rules proposed in this work significantly increase the success rate in DOCKing simulations. The database developed in this work is available at http://cimlcsext.cim.sld.cu:8080/screeningbrowser/.
The quality of communication about older patients between hospital physicians and general practitioners: a panel study assessment
Authors: Garåsen Helge , Johnsen Roar
Published: August 2007

Background

Optimal care of patients is dependent on good professional interaction between general practitioners and general hospital physicians. In Norway this is mainly based upon referral and discharge letters. The main objectives of this study were to assess the quality of the written communication between physicians and to estimate the number of patients that could have been treated at primary care level instead of at a general hospital.

Methods

This study comprised referral and discharge letters for 100 patients above 75 years of age admitted to orthopaedic, pulmonary and cardiological departments at the city general hospital in Trondheim, Norway. The assessments were done using a Delphi technique with two expert panels, each with one general hospital specialist, one general practitioner and one public health nurse using a standardised evaluation protocol with a visual analogue scale (VAS). The panels assessed the quality of the description of the patient's actual medical condition, former medical history, signs, medication, Activity of Daily Living (ADL), social network, need of home care and the benefit of general hospital care.

Results

While information in the referral letters on actual medical situation, medical history, symptoms, signs and medications was assessed to be of high quality in 84%, 39%, 56%, 56% and 39%, respectively, the corresponding information assessed to be of high quality in discharge letters was for actual medical situation 96%, medical history 92%, symptoms 60%, signs 55% and medications 82%. Only half of the discharge letters had satisfactory information on ADL. Some two-thirds of the patients were assessed to have had large health benefits from the general hospital care in question. One of six patients could have been treated without a general hospital admission. The specialists assessed that 77% of the patients had had a large benefit from the general hospital care; however, the general practitioners assessment was only 59%. One of four of the discharge letters did not describe who was responsible for follow-up care.

Conclusion

In this study from one general hospital both referral and discharge letters were missing vital medical information, and referral letters to such an extent that it might represent a health hazard for older patients. There was also low consensus between health professionals at primary and secondary level of what was high benefit of care for older patients at a general hospital.
Comparison of cooling methods to induce and maintain normo- and hypothermia in intensive care unit patients: a prospective intervention study
Authors: Hoedemaekers Cornelia W , Ezzahti Mustapha , Gerritsen Aico , van der Hoeven Johannes G
Published: August 2007

Background

Temperature management is used with increased frequency as a tool to mitigate neurological injury. Although frequently used, little is known about the optimal cooling methods for inducing and maintaining controlled normo- and hypothermia in the intensive care unit (ICU). In this study we compared the efficacy of several commercially available cooling devices for temperature management in ICU patients with various types of neurological injury.

Methods

Fifty adult ICU patients with an indication for controlled mild hypothermia or strict normothermia were prospectively enrolled. Ten patients in each group were assigned in consecutive order to conventional cooling (that is, rapid infusion of 30 ml/kg cold fluids, ice and/or coldpacks), cooling with water circulating blankets, air circulating blankets, water circulating gel-coated pads and an intravascular heat exchange system. In all patients the speed of cooling (expressed as°C/h) was measured. After the target temperature was reached, we measured the percentage of time the patient's temperature was 0.2°C below or above the target range. Rates of temperature decline over time were analyzed with one-way analysis of variance. Differences between groups were analyzed with one-way analysis of variance, with Bonferroni correction for multiple comparisons. A p < 0.05 was considered statistically significant.

Results

Temperature decline was significantly higher with the water-circulating blankets (1.33 ± 0.63°C/h), gel-pads (1.04 ± 0.14°C/h) and intravascular cooling (1.46 ± 0.42°C/h) compared to conventional cooling (0.31 ± 0.23°C/h) and the air-circulating blankets (0.18 ± 0.2°C/h) (p < 0.01). After the target temperature was reached, the intravascular cooling device was 11.2 ± 18.7% of the time out of range, which was significantly less compared to all other methods.

Conclusion

Cooling with water-circulating blankets, gel-pads and intravascular cooling is more efficient compared to conventional cooling and air-circulating blankets. The intravascular cooling system is most reliable to maintain a stable temperature.
Usefulness of C-reactive protein in monitoring the severe community-acquired pneumonia clinical course
Authors: Coelho Luís , Póvoa Pedro , Almeida Eduardo , Fernandes Antero , Mealha Rui , Moreira Pedro , Sabino Henrique
Published: August 2007

Background

The aim of the present study was to evaluate the C-reactive protein level, the body temperature and the white cell count in patients after prescription of antibiotics in order to describe the clinical resolution of severe community-acquired pneumonia.

Methods

A cohort of 53 consecutive patients with severe community-acquired pneumonia was studied. The C-reactive protein levels, body temperature and white cell count were monitored daily.

Results

By day 3 a C-reactive protein level 0.5 times the initial level was a marker of poor outcome (sensitivity, 0.91; specificity, 0.59). Patients were divided according to their C-reactive protein patterns of response to antibiotics, into fast response, slow response, nonresponse, and biphasic response. About 96% of patients with a C-reactive protein pattern of fast response and 74% of patients with a slow response pattern survived, whereas those patients with the patterns of nonresponse and of biphasic response had a mortality rate of 100% and 33%, respectively (P < 0.001). On day 3 of antibiotic therapy, a decrease in C-reactive protein levels by 0.31 or more from the previous day's level was a marker of good prognosis (sensitivity, 0.75; specificity, 0.85).

Conclusion

Daily C-reactive protein measurement after antibiotic prescription is useful in identification, as early as day 3, of severe community-acquired pneumonia patients with poor outcome. The identification of the C-reactive protein pattern of response to antibiotic therapy was useful in the recognition of the individual clinical course, either improving or worsening, as well as the rate of improvement, in patients with severe community-acquired pneumonia.
A New Approach to Estimate a Mixed Model–Based Ground Motion Prediction Equation
Authors: Tavakoli Behrooz , Pezeshk Shahram
Published: August 2007

A derivative-free approach based on a hybrid genetic algorithm (HGA) is proposed to estimate a mixed model–based ground motion prediction equation (attenuation relationship) with several variance components. First, a simplex search algorithm (SSA) is used to reduce the search domain to improve the convergence speed. Then, a genetic algorithm (GA) is employed to obtain the regression coefficients and the uncertainties of a predictive equation in a unified framework using one-stage maximum-likelihood estimation. The proposed HGA results in a predictive equation that best fits a given ground motion data set. The proposed HGA is able to handle changes in the functional form of the equation. To demonstrate the solution quality of the proposed HGA, the regression coefficients and the uncertainties of a test function based on a simulated ground motion data set are obtained. Then, the proposed HGA is applied to fit two functional attenuation forms to an actual data set of ground motion. For illustration, the results of the HGA are compared with those used by previous conventional methods. The results indicate that the HGA is an appropriate algorithm to overcome the shortcomings of the previous methods and to provide reliable and stable solutions.
Entropy generation in laminar natural convection from a constant temperature vertical plate in an infinite fluid
Authors: Ozkol I , Komurgoz G , Arikoglu A
Published: August 2007

In the work presented here, the entropy generation due to heat transfer and fluid flow has been carried out for laminar natural convection from a constant temperature vertical plate in an infinite fluid. Fluid flow and heat transfer characteristics on a constant temperature vertical plate are some of the fundamental problems in engineering.

The problem is discussed by considering the entropy generation profiles and the heat transfer irreversibility characteristics. An analytical expression, in terms of entropy generation number ( NG) and Bejan number ( Be) are derived in dimensionless form using velocity and temperature profiles. In addition, temperature profiles, entropy generation profiles and flow profiles characteristics, and relations between them are figured out. Obviously the maximum temperature line along the vertical plate corresponds to the maximum entropy generation line. The mechanism responsible for that is the enhancement in heat transfer rates and fluid friction in this region. Also, another important issue noticed during the analysis is the wall itself which emerges as a source of irreversibility or powerful entropy generator.
Magnetic fluid lubrication of porous-pivoted slider bearings with slip velocity
Authors: Ahmad N , Singh J. P.
Published: August 2007

A theoretical model of a magnetic fluid lubrication of porous-pivoted slider bearing with slip velocity has been considered to see the effect of various parameters. The expression of load capacity and centre of pressure has been obtained in terms of slip and permeability parameters. The dependence of load and centre of pressure on magnetic parameter, permeability parameter, and slip parameter has been studied graphically. Minimization of the slip parameter and permeability parameter has been discussed for the possible increase in the load capacity.
Asymmetric Catalytic Redox System: Tethered Bis(8-quinolinolato) (TBOx) Chromium(III/II) Complexes
Authors: Yamamoto Hisashi , Xia Guoyao
Published: August 2007

The TBOxCrIIICl/TBOxCrII system is ideal for catalytic asymmetric redox process. Because of the electron density of the TBOxH ligand high turnover numbers are expected, hence allowing decrease in the chromium catalyst loadings and acceleration of the reaction rate. High reactivity and high diastereo-/enantioselectivity are shown in asymmetric pinacol coupling reactions of aldehydes, asymmetric NH allylation reaction of aldehydes, asymmetric allenylation reactions of aldehydes, and some other reactions. These proceed exceedingly efficiently catalyzed by the TBOxCrIIICl redox system due to the well-designed chiral environment of the ligands and the cis-β configuration of the center Cr metal.
Different Magnetic Properties for Diastereomers of Alkoxide-bridged (β-Diketonato)ruthenium(III) Binuclear Complexes
Authors: Hashimoto Takeshi , Kawamoto Yuji , Ishitobi Yousuke , Sasaki Tatsuya , Fukuda Yutaka , Yamagishi Akihiko , Sato Hisako , Shimizu Kunio , Hayashita Takashi
Published: August 2007

Symmetric alkoxide-bridged diruthenium complexes [{Ru(acac)2}2(μ-OMe)2], which are obtained when [Ru(acac)2(CH3CN)2] reacts in methanol, can be separated into two diastereomers by column chromatography, and these diastereomers are found to exhibit different magnetic properties despite their structural similarities.
Modulation of individual steps in group I intron catalysis by a peripheral metal ion
Authors: Forconi Marcello , Piccirilli Joseph A. , Herschlag Daniel
Published: August 2007

Enzymes are complex macromolecules that catalyze chemical reactions at their active sites. Important information about catalytic interactions is commonly gathered by perturbation or mutation of active site residues that directly contact substrates. However, active sites are engaged in intricate networks of interactions within the overall structure of the macromolecule, and there is a growing body of evidence about the importance of peripheral interactions in the precise structural organization of the active site. Here, we use functional studies, in conjunction with published structural information, to determine the effect of perturbation of a peripheral metal ion binding site on catalysis in a well-characterized catalytic RNA, the Tetrahymena thermophila group I ribozyme. We perturbed the metal ion binding site by site-specifically introducing a phosphorothioate substitution in the ribozyme's backbone, replacing the native ligands (the pro-RP oxygen atoms at positions 307 and 308) with sulfur atoms. Our data reveal that these perturbations affect several reaction steps, including the chemical step, despite the absence of direct contacts of this metal ion with the atoms involved in the chemical transformation. As structural probing with hydroxyl radicals did not reveal significant change in the three-dimensional structure upon phosphorothioate substitution, the effects are likely transmitted through local, rather subtle conformational rearrangements. Addition of Cd2+, a thiophilic metal ion, rescues some reaction steps but has deleterious effects on other steps. These results suggest that native interactions in the active site may have been aligned by the naturally occurring peripheral residues and interactions to optimize the overall catalytic cycle.
A novel monoclonal antibody against human Argonaute proteins reveals unexpected characteristics of miRNAs in human blood cells
Authors: Nelson Peter T. , De Planell-Saguer Mariangels , Lamprinaki Stella , Kiriakidou Marianthi , Zhang Paul , O'Doherty Una , Mourelatos Zissimos
Published: August 2007

Argonaute (Ago) proteins bind to microRNA (miRNAs) and short interfering RNAs (siRNAs) and form the core components of effector complexes that mediate miRNA and siRNA function. Currently, there is a paucity of reliable antibodies against mammalian Ago proteins, thus precluding studies of endogenous Ago proteins from tissues. Here we report the development of 2A8, a novel anti-Ago monoclonal antibody that recognizes human and mouse Ago proteins and efficiently immunoprecipitates miRNAs. We report the characterization of 2A8 and its use to clone miRNAs from human brain and from preparations of human polymorphonuclear leukocytes (neutrophils), which revealed a prevalent miRNA with unusual features.
Phosphorothioate cap analogs stabilize mRNA and increase translational efficiency in mammalian cells
Authors: Grudzien-Nogalska Ewa , Jemielity Jacek , Kowalska Joanna , Darzynkiewicz Edward , Rhoads Robert E.
Published: August 2007

Capped RNAs synthesized by in vitro transcription have found wide utility for studying mRNA function and metabolism and for producing proteins of interest. We characterize here a recently synthesized series of cap analogs with improved properties that contain a sulfur substitution for a nonbridging oxygen in either the α-, β-, or γ-phosphate moieties, m27,2′-OGpppSG, m27,2′-OGppSpG, and m27,2′-OGpSppG, respectively. The new compounds were also modified at the 2′-O position of the m7Guo to make them anti-reverse cap analogs (ARCAs), i.e., they are incorporated exclusively in the correct orientation during in vitro transcription. Each of the S-ARCAs exists in two diastereoisomeric forms (D1 and D2) that can be resolved by reverse-phase HPLC. A major in vivo pathway for mRNA degradation is initiated by removal of the cap by the pyrophosphatase Dcp1/Dcp2, which cleaves between the α- and β-phosphates. Oligonucleotides capped with m27,2′-OGppSpG (D2) were completely resistant to hydrolysis by recombinant human Dcp2 in vitro, whereas those capped with m27,2′-OGppSpG (D1) and both isomers of m27,2′-OGpppSG were partially resistant. Luciferase mRNA capped with m27,2′-OGppSpG (D2) had a t1/2 of 257 min in cultured HC11 mammary epithelial cells compared with 86 min for m7Gp3G-capped mRNA. Luciferase mRNAs capped with m27,2′-OGppSpG (D1) and m27,2′-OGppSpG (D2) were translated 2.8-fold and 5.1-fold, respectively, more efficiently in HC11 cells than those capped with m7Gp3G. The greater yield of protein due to combining higher translational efficiency with longer t1/2 of mRNA should benefit applications that utilize RNA transfection such as protein production, anti-cancer immunization, and gene therapy.
Synthesis of polymers containing chiral 1,2-diamine derivatives and their application to asymmetric reactions
Authors: Itsuno Shinichi , Takahashi Miyuki , Arakawa Yukihiro , Haraguchi Naoki
Published: August 2007

Polymer-supported chiral 1,2-diamine derivatives have been prepared. The polymers containing free 1,2-diamine moiety were applied to enantioselective hydrogenation catalyst by combination with RuCl2-BINAP complex. Asymmetric hydrogenation of aromatic ketones was performed by means of the polymeric catalyst derived from these polymers to give the chiral secondary alcohols with high ee in quantitative conversion. The polymers containing 1,2-diamine monosulfonamide were applied to enantioselective transfer hydrogenation catalyst by combination with RuCl2-p-cymene complex. Asymmetric transfer hydrogenation of aromatic ketones was performed by means of the polymeric catalyst to afford the chiral secondary alcohols. A high level of enantioselectivities up to 99 % ee was attained in neat water by using the polymeric catalyst prepared from quaternary ammonium salt-type polymer support.
Asymmetric allylic substitution of cycloalkenyl esters in water with an amphiphilic resin-supported chiral palladium complex
Authors: Uozumi Yasuhiro
Published: August 2007

A novel homochiral phosphine ligand, (3R,9aS)[2-aryl-3-(2-diphenylphosphino)phenyl]tetrahydro-1H-imidazo[1,5-a]indole-1-one, was designed, prepared, and anchored onto an amphiphilic polystyrene-poly(ethylene glycol) copolymer (PS-PEG) resin. Catalytic asymmetric substitution of a racemic mixture of cycloalkenyl esters with carbon, nitrogen, and oxygen nucleophiles was achieved in water as the single reaction medium under heterogeneous conditions by using the PS-PEG resin-supported palladium-imidazoindole phosphine complex to give optically active substituted cycloalkenes with up to 99 % ee.
Using macroporous N-chlorosulfonamide S/DVB copolymer as an aid to iron removal from water
Authors: Bogoczek Romuald , Kociołek-Balawejder Elżbieta , Stanisławska Ewa , Żabska Agnieszka
Published: August 2007

The de-ironing of water is a basic stage in water-treating technology. Consequently, the oxidation of easily soluble Fe(II) to poorly soluble Fe(III) compounds is indispensible. In order to oxidize Fe(II) ions to Fe(III), a macromolecular and macroporous product in bead form was used: polystyrene cross-linked by divinylbenzene, which contains pendant N-chlorosulfonamide groups in both the sodium and hydrogen forms. To assist the process of removing residual iron from water, this polymer - a macromolecular analog of Chloramine T, containing more than 4.0 mequiv of active chlorine/g - was prepared, starting from the sulfonate cation exchanger Amberlyst 15 by a three-step transformation of its functional groups. The investigations were carried out using both the batchwise and column methods, and 0.0025 M as well as 0.02 M FeSO4 solutions with different acidity were used. We found that the oxidation of ferrous ions to ferric by N-chlorosulfonamide copolymer was effective and was favored by a low pH. The oxidative ability of the copolymer was 225 mg Fe(II)/g. We established that the oxidation reaction could be operated in two directions. In acidic media (pH < 2.5), Fe(III) ions remained in the solution as products of the reaction. The higher the pH, the more the poorly soluble ferric compounds sedimented in the inner structure of the copolymer beads. In this way, new hybrid materials were obtained, i.e., by ferrous/ferric oxides and hydroxides, by nanoparticles, modified materials which can serve as specific reacting sorbents and catalysts.
Synthesis and characterization of micrometer-sized molecularly imprinted spherical polymer particulates prepared via precipitation polymerization
Authors: Wang Jinfang , Cormack Peter A. G. , Sherrington David C. , Khoshdel Ezat
Published: August 2007

In this paper, the synthesis and characterization of molecularly imprinted spherical polymer particulates prepared via precipitation polymerization is described. The effects of the monomer and initiator concentrations and the solvent on the polymerizations were investigated systematically. Polymer microspheres with narrow size distributions and average diameters up to ca. 10 μm were prepared under optimized polymerization conditions. The morphologies of the microspheres were characterized by nitrogen sorption porosimetry and the molecular recognition properties of representative products evaluated in high-performance liquid chromatography (HPLC) mode. Imprinting effects were confirmed by analyzing the relative retentions of the analytes on imprinted and non-imprinted packed HPLC columns. Finally, two different agitation/mixing methods for precipitation polymerizations were compared. It was found that the use of a low-profile roller housed inside a temperature-controlled incubator had advantages over a rotavapor-based system. Overall, this study has served to highlight the attractiveness of precipitation polymerization for the routine production of molecularly imprinted polymers in a well-defined spherical particulate form via an efficient one-step synthetic process.
Biologically active polymeric sequestrants: Design, synthesis, and therapeutic applications
Authors: Dhal Pradeep K. , Huval Chad C. , Holmes-Farley S. Randall
Published: August 2007

In recent years, functional polymers exhibiting inherently biological activities have been receiving increasing attention as polymer-based human therapeutic agents. These polymeric drugs exhibit unique pharmaceutical properties that are fundamentally different from their traditional small-molecule counterparts. However, unlike polymeric drug delivery systems, examples of polymers possessing intrinsically therapeutic properties are relatively scarce. By virtue of their high-molecular-weight characteristics, these polymeric drugs can be confined to the gastrointestinal (GI) tract, where they can selectively recognize, bind, and remove target disease-causing substances from the body. Being confined to the GI tract and non-biodegradable, these polymeric drugs are free from toxic effects that are associated with traditional systemic drugs. This report highlights recent developments in the rational design and synthesis of appropriate functional polymers that have resulted in a number of promising polymer-based therapeutic agents, including some marketed products.
Self-supported chiral catalysts for heterogeneous enantioselective reactions
Authors: Ding Kuiling , Wang Zheng , Shi Lei
Published: August 2007

The development of a new strategy to immobilize the homogeneous chiral catalysts for enantioselective reactions is highly desirable in order to overcome some drawbacks of conventional approaches. In this lecture, a conceptually new strategy for heterogenization of homogeneous chiral catalysts (i.e., "self-supporting" approach) is presented. The concept focuses on the use of homochiral metal-organic coordination polymers generated by self-assembly of chiral multitopic ligands with metal ions as the heterogeneous catalysts, and thus obviating the need of any exogenous support. The application of this "self-supporting" strategy has been exemplified in heterogeneous catalysis of asymmetric carbonyl-ene, sulfoxidation, and epoxidation, as well as asymmetric hydrogenation reactions.
Future directions for the research and development of polyesters: From high-performance to environmentally friendly
Authors: Yamanaka Toru , Ohme Hiroyuki , Inoue Toshihide
Published: August 2007

We discuss the future directions for the research and development of polyester-based materials. In the discussion of polyesters as industrial materials, one direction is the development of high-performance materials. Poly(ethylene terephthalate) (PET), known as one of the most important polyesters, was developed early in the 1940s. We discuss two approaches to the development of high-performance materials suitable for injection-molding applications using PET units. The first approach is development of high-performance materials by copolymerization with bibenzoic acid (BB), which has a rigid structure, and the second approach is development of liquid-crystal polyesters (LCPs) with superior thermal resistance and excellent flowability using PET units. The other future direction for research and development is the targeting of environmentally friendly materials. Poly(lactic acid) (PLA), derived from bio-based materials, is a very important material because it can realize the carbon neutral cycles. Nevertheless, the practical properties of PLA itself are unsatisfactory compared to other plastics derived from fossil resources. We have developed PLA-based polymer alloys with various practical properties by utilizing a newly developed nanoalloy technology.
Highly active organosilane-based N-heterocyclic carbene-palladium complex immobilized on silica particles for the Suzuki reaction
Authors: Lee Sang-Myung , Yoon Hyo-Jin , Kim Jong-Ho , Chung Woo-Jae , Lee Yoon-Sik
Published: August 2007

1-Methyl-3-(3-trimethoxysilylpropyl)imidazolium chloride, [TMSPIM][Cl-], was synthesized as a precursor of N-heterocyclic carbene (NHC), which can be coordinated with palladium to give an organosilane-based bidentic NHC-Pd complex. The organosilane-based NHC-Pd complex was immobilized covalently on silica particles (NHC-Pd/silica) and then characterized by field emission/scanning electron microscopy (FE/SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIRS), and inductively coupled plasma/atomic emission spectroscopy (ICP/AES). The Suzuki reaction was performed as a model reaction to examine the catalytic activity of NHC-Pd/silica. NHC-Pd/silica exhibited excellent performance in the Suzuki reaction of various aryl halide derivatives (except for aryl chloride derivatives) with phenylboronic acid under mild conditions (room temperature and short reaction time). Moreover, the catalyst was recycled several times without any significant loss of catalytic activity in the Suzuki reaction.
Polysaccharide derivatives as useful chiral stationary phases in high-performance liquid chromatography
Authors: Chen Xiaoming , Yamamoto Chiyo , Okamoto Yoshio
Published: August 2007

The chromatographic separation of enantiomers using chiral stationary phases (CSPs) has significantly advanced. The esters and carbamates of polysaccharides coated on silica gel have been extensively studied and widely used as CSPs for high-performance liquid chromatography (HPLC). In order to overcome the strict solvent limitation on these coated CSPs, the preparation of a new generation of CSPs consisting of immobilized polysaccharide derivatives has become increasingly important. The universal solvent compatibility of the new CSPs provides flexibility in both analytical and preparative chromatographies.
Aggregation of biotinylated polymeric microspheres induced by interaction with avidin
Authors: Meng Qingbin , Li Zhanyong , Li Gang , Zhang Xu , An Yingli , Zhu X. X.
Published: August 2007

Monodisperse biotinylated poly(styrene-co-N-acryloxysuccinimide) microspheres were synthesized in aqueous solutions with a two-step method. Upon the addition of avidin solutions of different concentrations in phosphate buffer into the dispersed biotinylated microspheres, the microspheres aggregated rapidly due to the high binding affinity between biotin and avidin. The hydrodynamic diameter of the aggregates and the aggregation rate observed at given time intervals increased with increasing concentration of avidin. The composition of the microspheres and the incorporation of biotin were evidenced by Fourier transform infrared spectroscopy. The morphology, size distribution, and aggregation of the microspheres were studied by techniques such as scanning electron microscopy and dynamic light scattering.
Explanatory dictionary of key terms in toxicology (IUPAC Recommendations 2007)
Authors: Nordberg Monica , Duffus John H. , Templeton Douglas M.
Published: August 2007

The objective of the "Explanatory Dictionary of Key Terms in Toxicology" is to give full explanations of the meaning of toxicological terms chosen for their importance and complexity from the point of merging chemistry and toxicology. This requires a full description of the underlying concepts, going beyond a normal dictionary definition. Often linguistic barriers lead to problems in obtaining a common understanding of terminology at the international level and between disciplines. The explanatory comments should help to break down such barriers. The dictionary consists of about 68 terms chosen from the IUPAC "Glossary of Terms Used in Toxicokinetics" organized under 22 main headings. The authors hope that among the groups which will find this explanatory dictionary helpful are chemists, pharmacologists, toxicologists, risk assessors, regulators, medical practitioners, regulatory authorities, and everyone with an interest in the relationship of chemistry to toxicology. It should also facilitate the use of chemistry in relation to risk assessment.
Notes on Phase Extension
Authors: Frank Robert
Published: August 2007

1. The ingredients of locality

Since the early 1960s, one of the major goals of work in generative syntax has been to explain the locality properties of syntactic dependencies. Current accounts in the Minimalist framework derive locality from two basic notions. First, the syntactic relations that give rise to agreement and displacement are subjected to the Minimal Link Condition, which stipulates that such relations can obtain only in the absence of relevant intevening elements.
A ONECUT Homeodomain Protein Communicates X Chromosome Dose to SpecifyCaenorhabditis elegansSexual Fate by Repressing a Sex Switch Gene
Authors: Gladden John M , Meyer Barbara J
Published: August 2007

Sex is determined in Caenorhabditis elegans through a dose-dependent signal that communicates the number of X chromosomes relative to the ploidy, the number of sets of autosomes. The sex switch gene xol-1 is the direct molecular target of this X:A signal and integrates both X and autosomal components to determine sexual fate. X chromosome number is relayed by X signal elements (XSEs) that act cumulatively to repress xol-1 in XX animals, thereby inducing hermaphrodite fate. Ploidy is relayed by autosomal signal elements (ASEs), which counteract the single dose of XSEs in XO animals to activate xol-1 and induce the male fate. Our goal was to identify and characterize new XSEs and further analyze known XSEs to understand the principles by which a small difference in the concentration of an intracellular signal is amplified to induce dramatically different developmental fates. We identified a new XSE, the ONECUT homeodomain protein CEH-39, and showed that it acts as a dose-dependent repressor of xol-1 transcript levels. Unexpectedly, most other XSEs also repress xol-1 predominantly, but not exclusively, at the transcript level. The twofold difference in X dose between XO and XX animals is translated into the male vs. hermaphrodite fate by the synergistic action of multiple, independent XSEs that render xol-1 active or inactive, primarily through transcriptional regulation.
Patterns of Sequence Variability and Divergence at the diminutive Gene Region of Drosophila melanogaster: Complex Patterns Suggest an Ancestral Selective Sweep
Authors: Jensen Jeffrey D , Bauer DuMont Vanessa L , Ashmore Adeline B , Gutierrez Angela , Aquadro Charles F
Published: August 2007

To identify putatively swept regions of the Drosophila melanogaster genome, we performed a microsatellite screen spanning a 260-kb region of the X chromosome in populations from Zimbabwe, Ecuador, the United States, and China. Among the regions identified by this screen as showing a complex pattern of reduced heterozygosity and a skewed frequency spectrum was the gene diminutive (dm). To investigate the microsatellite findings, nucleotide sequence polymorphism data were generated in populations from both China and Zimbabwe spanning a 25-kb region and encompassing dm. Analysis of the sequence data reveals strongly reduced nucleotide variation across the entire gene region in both the non-African and the African populations, an extended haplotype pattern, and structured linkage disequilibrium, as well as a rejection of neutrality in favor of selection using a composite likelihood-ratio test. Additionally, unusual patterns of synonymous site evolution were observed at the second exon of this locus. On the basis of simulation studies as well as recently proposed methods for distinguishing between selection and nonequilibrium demography, we find that this “footprint” is best explained by a selective sweep in the ancestral population, the signal of which has been somewhat blurred via founder effects in the non-African samples.
Modulation ofCaenorhabditis elegansTranscription Factor Activity by HIM-8 and the Related Zinc-Finger ZIM Proteins
Authors: Sun Hongliu , Nelms Brian L , Sleiman Sama F , Chamberlin Helen M , Hanna-Rose Wendy
Published: August 2007

The previously reported negative regulatory activity of HIM-8 on the Sox protein EGL-13 is shared by the HIM-8-related ZIM proteins. Furthermore, mutation of HIM-8 can modulate the effects of substitution mutations in the DNA-binding domains of at least four other transcription factors, suggesting broad regulatory activity by HIM-8.