bluuebunny/crossref_metadata_2025 huggingface dataset:
Bimatoprost, a novel efficacious ocular hypotensive drug now recognized as a member of a new class of agents called prostamides
Authors: Burk Robert M. , Woodward David F.
Published: October 2007

Pursuit of a new FP‐agonist prodrug led to the identification of an interesting series of neutral C1‐substituted prostaglandin F2α analogues. Although these initial analogues were devoid of any inherent pharmacological activity at the FP‐receptor, two compounds AGN‐190910 and AGN‐191129, were found to have pronounced effects in lowering intraocular pressure (IOP) in normotensive dogs and monkeys. The cat iris sphincter assay was quickly developed as a primary screen for these analogues, leading to rapid identification of AGN‐192024 (17‐phenyl PGF2α ethyl amide, bimatoprost). While bimatoprost is structurally similar to naturally occurring mammalian hormones of the prostanoid family, surprisingly it demonstrates no significant activity at any of the known prostanoid receptors. Furthermore, results of considerable additional pharmacological studies provide evidence that it may indeed act through a unique receptor yet to be identified. The effect of Bimatoprost on lowering IOP has also been found to be unique in comparison to prostanoids. Bimatoprost reduces human IOP by increasing aqueous humor outflow through a dual mechanism of action where it improves both pressure‐dependent and pressure‐independent outflow pathways. First introduced to the market in 2002, bimatoprost is currently the most potent single therapy available for control of ocular hypertension. Drug Dev Res 68:147–155, 2007. ©2007 Wiley‐Liss, Inc.
Platforms and networks in triterpenoid pharmacology
Authors: Sporn Michael B. , Liby Karen , Yore Mark M. , Suh Nanjoo , Albini Adriana , Honda Tadashi , Sundararajan Chitra , Gribble Gordon W.
Published: October 2007

Using the pentacyclic, naturally occurring triterpenoids, oleanolic, ursolic, and betulinic acids, as starting materials, we have developed a new series of multifunctional drugs for potential clinical use. These agents have anti‐inflammatory, anti‐oxidative, anti‐proliferative, pro‐apoptotic, and differentiating activities. Two synthetic oleanane triterpenoids, 2‐cyano‐3,12‐dioxooleana‐1,9(11)‐dien‐28‐oic acid (CDDO) and its C‐28 methyl ester (CDDO‐Me), are presently in Phase I clinical trials in cancer patients. Three themes are emphasized in this review: (1) The importance of the unique structures of the triterpenoid platforms that have been used as a start for new synthesis; (2) The concept that these new drugs interact with entire physiological networks, rather than solely with single molecular targets; and (3) The coupling in real time between the triterpenoid platforms and the physiological networks with which they interact, as seen in the reversibility of the Michael reactions, which mediate their activity. We suggest that further development of such new, multifunctional drugs will most likely occur in the more flexible environment of small biotech or pharmaceutical companies. Drug Dev Res 68:174–182, 2007. © 2007 Wiley‐Liss, Inc.
A circuitous pharmaceutical journey to Liliput
Authors: Bridges Alex
Published: October 2007

The author describes some of his meandering through 35 years of organic and medicinal chemistry, with emphasis on nearly a quarter of a century in the pharmaceutical industry. Special attention is paid to the not exactly voluntary transition from being an allegedly important cog at a pharmaceutical leviathan, to a possibly useful cog at a pharmaceutical minnow. This is a transition that many in the industry have already made, and many more will be making in the future, whether they wish to do so or not. The author's view of said process is the main content of this article. The habitual sense of loss that accompanies such a change is described, along with the realization that although much good disappears when a well‐running team is scattered to the four winds, most of the remaining loss is bells and whistles, pomp and circumstance, and what may be given back is the primacy of science, and the possibility of listening and responding again to “the still sad music of humanity,” as opposed to third‐rate business school gibberish. Recommended reading: Tennyson's “Ulysses.”. Drug Dev Res 68:197–204, 2007. © 2007 Wiley‐Liss, Inc.
Derailed regulates development of the Drosophila neuromuscular junction
Authors: Liebl Faith L.W. , Wu Yuping , Featherstone David E. , Noordermeer Jasprina N. , Fradkin Lee , Hing Huey
Published: October 2007

Neural function is dependent upon the proper formation and development of synapses. We show here that Wnt5 regulates the growth of the Drosophila neuromuscular junction (NMJ) by signaling through the Derailed receptor. Mutations in both wnt5 and drl result in a significant reduction in the number of synaptic boutons. Cell‐type specific rescue experiments show that wnt5 functions in the presynaptic motor neuron while drl likely functions in the postsynaptic muscle cell. Epistatic analyses indicate that drl acts downstream of wnt5 to promote synaptic growth. Structure–function analyses of the Drl protein indicate that normal synaptic growth requires the extracellular Wnt inhibitory factor domain and the intracellular domain, which includes an atypical kinase. Our findings reveal a novel signaling mechanism that regulates morphology of the Drosophila NMJ. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2008
Nickel Complexes with N2O Donor Ligands: Syntheses, Structures, Catalysis and Magnetic Studies (Eur. J. Inorg. Chem. 32/2007)
Authors: Chakraborty Jishnunil , Nandi Mahasweta , Mayer‐Figge Heike , Sheldrick William S. , Sorace Lorenzo , Bhaumik Asim , Banerjee Pradyot
Published: October 2007

The cover picture shows how a novel tetranuclear NiII complex [Ni4L41(μ‐tp‐κ4‐O)(H2O)2(μ‐tp‐κ2‐O)]·2C2H5OH·CH3OH·3H2O [L1 = N‐(3‐aminopropyl)‐5‐bromosalicylaldimine] acts as an active catalyst for the partial oxidation of cyclohexene into its epoxide product when it is immobilized over a network of hexagonal mesoporous silica. Herein the catalytic sites allow the formation of epoxide over their surfaces. tert‐Butyl hydroperoxide acts as an oxidant for the partial oxidation process. A dinuclear unit is formed, in which the NiII is bridged by a phenolato group, and two such units are connected through a terephthalate moiety to form a tetranuclear nickel(II) complex. The tetranuclear units are connected to each other by another terephthalate moiety in its bis(monodentate) mode to form one‐dimensional networks. Details are described in the article by P. Banerjee et al. on p. 5033 ff. The artwork was designed by Mr. Jishnunil Chakraborty and Mr. Gopal Das.
Determining the global DNA methylation status of rat according to the identifier repetitive elements
Authors: Kim Hwan‐Hee , Park Jung‐Hoon , Jeong Kyoung‐Sin , Lee Suman
Published: October 2007

A large portion of the genome represents repetitive elements. Identifier (ID) elements, the major elements of short interspersed repetitive elements, are widespread with about 150 000 copies in the rat genome. Each ID element contains six CpG dinucleotides, which might account for the global methylation status of rat. We validated the CpG methylation of the ID elements by various methods. The methylation of one CpG site (CpG‐3) of the ID element was investigated by performing pyrosequencing. The methylation percentage of the CpG‐3 site was 53.6% (SD = 2.2) on average from six rat tissues with blood, but 24.6% (SD = 1.0) in rat pheochromocytoma, PC‐12, cell line. This CpG‐3 methylation was further verified by whole genome amplification (WGA), 5‐azacytidine treatment, and proportional mixing of rat WGA genomic DNA (gDNA) with liver gDNA. Methylation‐sensitive restriction enzyme PCR method showed that three other CpG sites (CpG‐1, CpG‐4, and CpG‐5) within the ID element were also methylated (about 60%) in rat gDNA, but not in WGA gDNA. The ID elements may be good candidates for routine analysis of the global DNA methylation changes of rat for pharmaceutical treatment and their use can make basic epigenetic research possible with high accuracy.
“Paterniplex”, a highly discriminative decaplex STR multiplex tailored for investigating special problems in paternity testing
Authors: Betz Thomas , Immel Uta‐Dorothee , Kleiber Manfred , Klintschar Michael
Published: October 2007

The goal of the study was to develop a STR multiplex (“Paterniplex”) that is – as supplement to commercially available multiplex kits like the Identifiler® kit (Applied Biosystems, Foster City, CA) – suitable for solving complex paternity cases such as deficiency cases or cases with mutations. The Paterniplex comprises the nine highly polymorphic STRs D8S1132, D7S1517, D10S2325, D12S391, Se33, D17S976, Penta E, Penta D and FGA in addition to Amelogenin as sex determination marker. The loci were selected because of their high degree of polymorphism (higher than that of the widely used TH01 marker). Only one locus, FGA, is shared with the Identifiler kit to avoid sample mix up. The study further gives details on the population genetics of the loci in a German Caucasian population (allelic distribution, Hardy–Weinberg Equilibrium and forensic efficiency markers such as the Discriminating Power) and three examples for cases that could not be solved using commercially available kits alone, but using the Paterniplex in addition to a commercial kit.
CE methods for the determination of non‐protein amino acids in foods
Authors: Castro‐Puyana María , Crego Antonio Luis , Marina María Luisa , García‐Ruiz Carmen
Published: October 2007

In addition to the 20 amino acids universally distributed as protein constituents in living organisms, there are other amino acids of non‐protein origin that can be found in foods. The determination of these non‐protein amino acids is interesting since they can be indicative of the quality and safety of foods. This work presents for the first time an updated and comprehensive review devoted to show the possibilities of capillary electrophoresis for the determination of non‐protein amino acids in food samples. The results reported have been classified according to the chemical structure of the non‐protein amino acid studied. Separation conditions as well as detection systems used have been detailed since most of these amino acidic compounds do not posses chromophore groups detectable by conventional UV‐Vis detection, being in this case necessary a previous derivatization step. Finally, the application of microchip electrophoresis to the determination of non‐protein amino acids in foodstuffs is also included in this review.
A practical and cost‐effective mutation scanning‐based approach for investigating genetic variation in Cryptosporidium
Authors: Jex Aaron R. , Whipp Margaret , Campbell Bronwyn E. , Cacciò Simone M. , Stevens Melita , Hogg Geoff , Gasser Robin B.
Published: October 2007

In the present study, we used a mutation scanning‐targeted sequencing approach to assess variation in part (pgp60) of the 60 kDa glycoprotein (gp60) gene among Cryptosporidium samples from humans in Victoria, Australia. Two nuclear ribosomal loci (the small subunit rRNA gene and the second internal transcribed spacer) were used to identify the samples as Cryptosporidium hominis (n = 74), Cryptosporidium parvum (n = 23) or Cryptosporidium meleagridis (n = 1). In total, nine distinct pgp60 sequences were identified (three C. hominis, five C. parvum and one C. meleagridis). Phylogenetic analyses of the pgp60 sequence data, employing well‐defined reference sequences for comparison, allowed the genotypic and subgenotypic classification of samples. The C. hominis samples were classified as Ib A10G2R2, Id A15G1R2, and a new genotype, designated Ib2, was identified subgenotypically as A18G1R4. The C. parvum samples were classified as IIa A18G3R1, IIa A20G3R1, IIa A22G3R1, IIa A23G3R1 and IIc A5G3R2. These findings suggested that the C. hominis metapopulation is largely homogeneous, consisting of a single dominant genotype, Ib A10G2R2, whereas the C. parvum metapopulation is considerably more heterogeneous, with no single dominant genotype. The greater level of genetic heterogeneity found among the C. parvum samples, despite the smaller sample size, may relate to the zoonotic infection pattern of this species, which would be reflective of a greater number of possible infection sources. The present mutation scanning approach, coupled with targeted sequencing of genetically distinct representatives, is a practical, cost‐effective tool for large‐scale population genetic and epidemiological studies of Cryptosporidium and other eukaryotic organisms.

Nucleotide sequence data reported in this paper are available in GenBank accession nos. EU164805–EU164813
Large‐volume sample stacking for the analysis of seven β‐lactam antibiotics in milk samples of different origins by CZE
Authors: Bailón‐Pérez M. Isabel , García‐Campaña Ana M. , Cruces‐Blanco Carmen , del Olmo Iruela Monsalud
Published: October 2007

A method for the simultaneous determination of eight β‐lactam antibiotics (nafcillin, cloxacillin, oxacillin, dicloxacillin, ampicillin, amoxicillin, and penicillin G) in fortified milk samples of different origins has been proposed by using CZE with diode‐array detection (CZE‐DAD). Optimum separation was obtained on a 64.5 cm×75 μm bubble cell capillary using 175 mM Tris buffer with 20% ethanol at pH 8.0. Methylparaben has been used as an internal standard (IS). Taking into account the lack of sensitivity of the UV–Vis detection, a solvent extraction/SPE method was applied for off‐line preconcentration and sample cleanup, and also an on‐line preconcentration methodology, such as large‐volume sample stacking (LVSS) with polarity switching, was developed, providing LODs ranging from 2 to 10 μg/L. The method permits the quantification of these residues below the levels established in milk by the EU Regulation. Satisfactory recoveries ranging from 86 to 93% were also obtained in milk samples of different origins.
CE‐MS of zein proteins from conventional and transgenic maize
Authors: Erny Guillaume L. , Marina Maria Luisa , Cifuentes Alejandro
Published: October 2007

In this work, an original CE‐MS method has been developed to analyze the complex zein protein fractions from maize. A thorough optimization of: (i) zein protein extraction, (ii) CE separation, and (iii) electrospray‐MS (ESI‐MS) detection is carried out in order to obtain highly informative CE‐MS profiles of this fraction. The developed CE‐MS method provides good separation of multiple zein proteins based on their electrophoretic mobilities as well as adequate characterization of these proteins based on their Mr. Zein proteins with small Mr differences (below 100 Da) were easily separated and successfully analyzed by CE‐MS. Thus, apart of the so‐called 15‐kDa‐β‐zein and 16‐kDa‐γ‐zein, which are demonstrated to be formed by a heterogeneous group of proteins, numerous α‐zeins belonging to the 19‐ and 22‐kDa fraction were also identified for the first time in this work. The usefulness of this CE‐MS method was corroborated by comparing the zein‐protein fingerprints of various maize lines including transgenic and their corresponding nontransgenic isogenic lines cultivated under the same conditions.
Analysis of opioid peptides by on‐line SPE‐CE‐ESI‐MS
Authors: Hernández Elena , Benavente Fernando , Sanz‐Nebot Victoria , Barbosa José
Published: October 2007

In this study, SPE‐CE‐ESI‐MS is explored for the preconcentration and separation of dilute solutions of six opioid peptides. First, a CE‐ESI‐MS methodology was developed and validated. LODs of around 1 μg/mL were obtained for all the studied peptides. For SPE‐CE‐ESI‐MS experiments, a home‐made SPE microcartridge containing a C18 sorbent was constructed near the inlet of the separation capillary. After optimizing the on‐line preconcentration methodology, LODs between 10 and 0.1 ng/mL were achieved. Repeatability, reproducibility, durability of the microcartridges and linearity of the SPE‐CE‐ESI‐MS methodology were also investigated and compared to the values obtained by CE‐ESI‐MS. Finally, human plasma samples fortified with opioid peptides were analyzed by SPE‐CE‐ESI‐MS in order to show the potential of the methodology for the analysis of biological fluids.
Gene profile analysis implicates Klotho as an important contributor to aging changes in brain white matter of the rhesus monkey
Authors: Duce James A. , Podvin Sonia , Hollander William , Kipling David , Rosene Douglas L. , Abraham Carmela R.
Published: October 2007

Conventional studies of brain changes in normal aging have concentrated on gray matter as the locus for cognitive dysfunction. However, there is accumulating evidence from studies of normal aging in the rhesus monkey that changes in white matter may be a more critical factor in cognitive decline. Such changes include ultrastructural and biochemical evidence of myelin breakdown with age, as well as more recent magnetic resonance imaging of global loss of forebrain white matter volume and magnetic resonance diffusion tension imaging evidence of increased diffusivity in white matter. Moreover, many of these white matter changes correlate with age‐related cognitive dysfunction. Based on these diverse white matter findings, the present work utilized high‐density oligonucleotide microarrays to assess gene profile changes associated with age in the white matter of the corpus callosum. This approach identified several classes of genes that were differentially expressed in aging. Broadly characterized, these genes were predominantly related to an increase in stress factors and a decrease in cell function. The cell function changes included increased cell cycle inhibition and proteolysis, as well as decreased mitochondrial function, signal transduction, and protein translation. While most of these categories have previously been reported in functional brain aging, this is the first time they have been associated directly with white matter. Microarray analysis has also enabled the identification of neuroprotective response pathways activated by age in white matter, as well as several genes implicated in lifespan. Of particular interest was the identification of Klotho, a multifunctional protein that regulates phosphate and calcium metabolism, as well as insulin resistance, and is known to defend against oxidative stress and apoptosis. Combining the findings from the microarray study enabled us to formulate a model of white matter aging where specific genes are suggested as primary factors in disrupting white matter function. In conclusion, the overall changes described in this study could provide an explanation for aging changes in white matter that might be initiated or enhanced by an altered expression of life span associated genes such as Klotho. © 2007 Wiley‐Liss, Inc.
Age‐dependent accumulation of ubiquitinated 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase in myelin lipid rafts
Authors: Hinman Jason D. , Chen Ci‐Di , Oh Sun‐Young , Hollander William , Abraham Carmela R.
Published: October 2007

Changes in brain white matter are prominent features of the aging brain and include glial cell activation, disruption of myelin membranes with resultant reorganization of the molecular components of the node of Ranvier, and loss of myelinated fibers associated with inflammation and oxidative stress. In previous studies, overexpression of CNP, a key myelin protein, was implicated in age‐related changes in myelin and axons. Here we examine the extent of CNP accumulation in brain white matter and isolated myelin of aged rhesus monkeys and its relationship to CNP degradation and partitioning in myelin. With age, excess CNP is found in myelin and throughout brain white matter accompanied by proteolytic fragments of CNP. These increases occur in the absence of changes in CNP mRNA levels. Using a combination of 2D electrophoresis, immunoprecipitation, and mass spectrometry analysis, ubiquitinated CNP was demonstrable in the Triton X‐100 insoluble lipid raft associated fractions of myelin isolated from rhesus monkeys. Further, using ubiquitin‐mediated fluorescence complementation (UbFC), ubiquitinated CNP was visualized by microscopy in both COS‐7 and MO3.13 cells and by immunoblot in MO3.13 cells and appears to at least partially localize within lipid rafts. The findings suggest that incomplete degradation of CNP due to failure of the proteasomal system and aberrant degradation by calpain‐1 leads to age‐related CNP accumulation and proteolysis. In sum, we suspect these phenomena result in age‐related dysfunction of CNP in the lipid raft, which may lead to myelin and axonal pathology. © 2007 Wiley‐Liss, Inc.
Protective effects of cysteine, methionine and vitamin C on the stomach in chronically alcohol treated rats
Authors: Amanvermez Ramazan , Tunçel Özgür K. , Demir Şerif , Kefeli Mehmet , Bek Yüksel , Çelik Cemil
Published: October 2007

A chronic intake of high dose alcohol may cause oxidative stress and inflammation in the stomach. It is hypothesized that cysteine‐methionine and vitamin C may neutralize harmful compounds while potentiating the antioxidant capacity of the cell or tissue. The experimental animals were fed regular diets and were maintained for 90 days in the control group, the alcoholic group, which was given 2.5 g of 50% ethanol kg−1body wt. administered intragastrically every other day, or the alcoholic with antioxidant supplement group, to whom 2.5 g of 50% ethanol kg−1body wt. + a solution that contained 200 mg vitamin C, 100 mg cysteine and 100 mg methionine was administered intragastrically every other day. After the treatments, the stomach was taken for pathological and biochemical analysis. The stomach of the alcoholic group rats had higher scores of pathological findings compared with the control group, whereas the scores of the antioxidant‐supplemented group were lower than the alcoholic group. In addition, the oxidized protein and lipid content in the stomachs of the alcoholic group were significantly higher than the control, but antioxidant supplementation lowered the amount of oxidation in the antioxidant supplemented group. The amount of stomach glutathione in the alcoholic group was higher than that of the control and antioxidant‐supplemented groups. Interestingly, the level of total thiol in the stomach tissue of rats with antioxidant supplement was statistically higher than that of the control and alcoholic groups. In conclusion, the scores of the pathological findings in the stomach of rats with the antioxidant supplement were lower than the chronic alcohol‐treated rats, albeit the amount of total thiol was increased in this group. Moreover, chronic alcohol treatment led to an increase in the level of lipid and protein oxidation in the stomach tissue of rats. A simultaneous intake of ascorbate/l‐cys/l‐met along with ethanol attenuated the amount of oxidation which suggested that cysteine‐methionine and vitamin C could play a protective role in the stomach against oxidative damage resulting from chronic alcohol ingestion. Copyright © 2007 John Wiley & Sons, Ltd.
Inhibition of jet fuel aliphatic hydrocarbon induced toxicity in human epidermal keratinocytes
Authors: Inman A. O. , Monteiro‐Riviere N. A. , Riviere J. E.
Published: October 2007

Jet propellant (JP)‐8, the primary jet fuel used by the U.S. military, consists of hydrocarbon‐rich kerosene base commercial jet fuel (Jet‐A) plus additives DC1‐4A, Stadis 450 and diethylene glycol monomethyl ether. Human epidermal keratinocytes (HEK) were exposed to JP‐8, aliphatic hydrocarbon (HC) fuel S‐8 and aliphatic HC pentadecane (penta), tetradecane (tetra), tridecane (tri) and undecane (un) for 5 min. Additional studies were conducted with signal transduction pathway blockers parthenolide (P; 3.0 µm), isohelenin (I; 3.0 µm), SB 203580 (SB; 13.3 µm), substance P (SP; 3.0 µm) and recombinant human IL‐10 (rHIL‐10; 10 ng ml−1). In the absence of inhibitors, JP‐8 and to a lesser extent un and S‐8, had the greatest toxic effect on cell viability and inflammation suggesting, as least in vitro, that synthetic S‐8 fuel is less irritating than the currently used JP‐8. Each inhibitor significantly (P < 0.05) decreased HEK viability. DMSO, the vehicle for P, I and SB, had a minimal effect on viability. Overall, IL‐8 production was suppressed at least 30% after treatment with each inhibitor. Normalizing data relative to control indicate which inhibitors suppress HC‐mediated IL‐8 to control levels. P was the most effective inhibitor of IL‐8 release; IL‐8 was significantly decreased after exposure to un, tri, tetra and penta but significantly increased after JP‐8 exposure compared with controls. Inhibitors were not effective in suppressing IL‐8 release in JP‐8 exposures to control levels. This study shows that inhibiting NF‐κB, which appears to play a role in cytokine production in HC‐exposed HEK in vitro, may reduce the inflammatory effect of HC in vivo. Copyright © 2007 John Wiley & Sons, Ltd.
Beneficial drugs for liver diseases
Authors: Muriel Pablo , Rivera‐Espinoza Yadira
Published: October 2007

Liver diseases are a major problem of worldwide proportions. However, the number of drugs actually used successfully in humans is very small. In this review some of the most promising/studied drugs utilized for liver diseases were chosen and analysed critically from the basic to the clinical point of view. Antiviral agents are not discussed because excellent reviews have appeared on this topic. The compounds/preparations described herein are, alphabetically: colchicine, corticosteroids, curcumin, glycyrrhizin, interferons (for their antifibrotic properties), Liv 52, nitric oxide, resveratrol, silymarin, sulfoadenosylmethionine, and thalidomide. Colchicine and corticosteroids have been studied extensively in animals and humans; most clinical studies suggest that these compounds are not useful in the treatment of liver diseases. Glycyrrhizin is an herbal medicine with several components that has interesting hepatoprotective properties in patients with subacute liver failure but deserves more prospective controlled trials. Interferon has shown interesting antifibrotic properties in animals and humans; prospective studies on their antifibrotic/fibrolytic activity are required. Curcumin, resveratrol and thalidomide are very attractive newly discovered protective and curative compounds on experimental hepatic diseases. Their mechanism of action is associated with the ability to down‐regulate NF‐κB and to decrease pronecrotic and profibrotic cytokines. Unfortunately, clinical studies are lacking. Sulfoadenosylmethionine and silymarin are also promising drugs utilized mainly in cholestasis but the benefits can be expanded if more controlled trials are performed. The future is to carry out controlled prospective double‐blind multicenter studies with the newly discovered drugs with proven beneficial effects on animals. Fundamental hepatobiology should also be encouraged. Copyright © 2007 John Wiley & Sons, Ltd.
Photochemistry studied with ab initio orbital‐correlation and state‐correlation plots: Classic cyclobutene ring opening, and the reaction of N2 with photoexcited O2
Authors: Shi Huancong , Roettger David C. , East Allan L. L.
Published: October 2007

Pericyclic reaction theory arose from ideas presented in 1965, based on orbital‐energy correlation diagrams (Woodward and Hoffmann) and state‐energy correlation diagrams (Longuet‐Higgins and Abrahamson). Here we have used ab initio complete‐active‐space self‐consistent field (CASSCF) calculations to generate such diagrams. First we present diagrams for the classic case of cyclobutene ring opening, to demonstrate agreement between the CASSCF results and the classic diagrams of both Woodward/Hoffmann and Longuet‐Higgins/Abrahamson. Then we present diagrams for the more difficult cases of N2 + photoexcited O2, to produce either 2 NO or NNO + O. These N2 + O2 cases feature significant electron reorganization, for which elementary pencil‐and‐paper diagrams are less accurate. Finally, the benefits and limitations of such diagrams for predicting photochemistry are briefly discussed. © 2007 Wiley Periodicals, Inc. J Comput Chem 2008
Combination of molecular dynamics method and 3D‐RISM theory for conformational sampling of large flexible molecules in solution
Authors: Miyata Tatsuhiko , Hirata Fumio
Published: October 2007

We have developed an algorithm for sampling the conformational space of large flexible molecules in solution, which combines the molecular dynamics (MD) method and the three‐dimensional reference interaction site model (3D‐RISM) theory. The solvent‐induced force acting on solute atoms was evaluated as the gradient of the solvation free energy with respect to the solute‐atom coordinates. To enhance the computation speed, we have applied a multiple timestep algorithm based on the RESPA (Reversible System Propagator Algorithm) to the combined MD/3D‐RISM method. By virtue of the algorithm, one can choose a longer timestep for renewing the solvent‐induced force compared with that of the conformational update. To illustrate the present MD/3D‐RISM simulation, we applied the method to a model of acetylacetone in aqueous solution. The multiple timestep algorithm succeeded in enhancing the computation speed by 3.4 times for this model case. Acetylacetone possesses an intramolecular hydrogen‐bonding capability between the hydroxyl group and the carbonyl oxygen atom, and the molecule is significantly stabilized due to this hydrogen bond, especially in gas phase. The intramolecular hydrogen bond was kept intact during almost entire course of the MD simulation in gas phase, while in the aqueous solutions the bond is disrupted in a significant number of conformations. This result qualitatively agrees with the behavior on a free energy barrier lying upon the process for rotating a torsional degree of freedom of the hydroxyl group, where it is significantly reduced in aqueous solution by a cancellation between the electrostatic interaction and the solvation free energy. © 2007 Wiley Periodicals, Inc. J Comput Chem 2008
Determination of spin‐orbit coupling contributions in the framework of density functional theory
Authors: Chiodo Sandro , Russo Nino
Published: October 2007

We present a noniterative method to calculate spin‐orbit coupling by means of a theoretical approach that provides the use of the full Breit–Pauli operator. This method was applied to compute one and two‐electron spin‐orbit coupling contributions between singlet and triplet, and doublet and doublet states, respectively. These states have been represented by monodeterminantal wave functions and optimized using the PW91 gradient‐corrected exchange‐correlation functional and the hybrid B3LYP one. They have been supplied by the conventional density functional theory packages, and thus coupled by our spin‐orbit coupling code. Different size basis sets have been employed and the obtained results have been compared with the corresponding ones provided by some of the already existing methods and with the experimental data. They have been found to be in good quantitative agreement. © 2007 Wiley Periodicals, Inc. J Comput Chem 2008
Improved efficiency of focal point conformational analysis with truncated correlation consistent basis sets
Authors: Kahn Kalju , Kahn Iiris
Published: October 2007

It has been suggested that the computational cost of correlated ab initio calculations could be reduced efficiently by using truncated basis sets on hydrogen atoms (Mintz et al., J Chem Phys 2004, 121, 5629). We now explore this proposal in the context of conformational analysis of small molecules, such as hydrogen peroxide, dimethyl ether, ethyl methyl ether, formic acid, methyl formate, and several small alcohols. It is found that truncated correlation consistent basis sets that lack certain higher angular momentum functions on hydrogen atoms offer accuracy similar to traditional Dunning's basis sets for conformational analysis. Combination of such basis sets with the basis set extrapolation technique to estimate Hartree–Fock and Møller–Plesset second order energies provides composite extrapolation model chemistries that are significantly more accurate and faster than analogous single point calculations with traditional correlation consistent basis sets. Root mean square errors of best composite extrapolation model chemistries on the used set of molecules are within 0.03 kcal/mol of traditional focal point conformational energies. The applicability of composite extrapolation methods is illustrated by performing conformational analysis of tert‐butanol and cyclohexanol. For comparison, conformational energies calculated with popular molecular mechanics force fields are also given. © 2007 Wiley Periodicals, Inc. J Comput Chem 2008
A new method for determining the interfacial molecules and characterizing the surface roughness in computer simulations. Application to the liquid–vapor interface of water
Authors: Pártay Lívia B. , Hantal György , Jedlovszky Pál , Vincze Árpád , Horvai George
Published: October 2007

A new method is presented to identify the truly interfacial molecules at fluid/fluid interfaces seen at molecular resolution, a situation that regularly occurs in computer simulations. In the new method, the surface is scanned by moving a probe sphere of a given radius along a large set of test lines that are perpendicular to the plane of the interface. The molecules that are hit by the probe spheres are regarded as interfacial ones, and the position of the test spheres when they are in contact with the interfacial molecules give an estimate of the surface. The dependence of the method on various parameters, in particular, on the size of the probe sphere is discussed in detail. Based on the list of molecules identified as truly interfacial ones, two measures of the molecular scale roughness of the surface are proposed. The bivariate distribution of the lateral and normal distances of two points of the interface provides a full description of the molecular scale morphology of the surface in a statistical sense. For practical purposes two parameters related to the dependence of the average normal distance of two surface points on their lateral distance can be used. These two parameters correspond to the frequency and amplitude of the surface roughness, respectively. The new method is applied for the analysis of the molecular level structure of the liquid–vapor interface of water. As an immediate result of the application of the new method it is shown that the orientational preferences of the interfacial water molecules depend only on the local curvature of the interface, and hence the molecules located at wells of concave curvature of the rippled surface prefer the same orientations as waters located at the surface of small apolar solutes. The vast majority of the truly interfacial molecules are found to form a strongly percolating two‐dimensional hydrogen bonded network at the surface, whereas no percolation is observed within the second molecular layer beyond the surface. © 2007 Wiley Periodicals, Inc. J Comput Chem 2008
Chemoenzymatic synthesis of chiral carboxylic acids via nitriles
Authors: Benz Peter , Muntwyler Rene , Wohlgemuth Roland
Published: October 2007

BACKGROUND: Enantiomerically pure 1,4‐benzodioxane‐2‐carboxylic acid derivatives are useful building blocks for the synthesis of pharmaceuticals and biologically active compounds whose interaction with their biological target (enzyme, receptor) depends very much on the absolute configuration of the chiral carbon at the 2‐position.

The aim of the present work is to investigate the route to racemic nitriles and the subsequent selective enzymatic hydrolysis by nitrilase to optically active 1,4‐benzodioxane‐2‐carboxylic acid and 6‐formyl‐1,4‐benzodioxane‐2‐carboxylic acid.

RESULTS: A range of microbial nitrilases from Rhodococcus, Alcaligenes and Pseudomonas strains have been prepared and screened for the desired biotransformations using a chiral high performance liquid chromatography (HPLC) analytical method. The nitrilase from Alcaligenes faecalis ATCC 8750 showed the highest and the nitrilase from Rhodococcus rhodochrous NCIMB 11216 the lowest activity towards 2‐cyano‐6‐formyl‐1,4‐benzodioxane. Lyophilised cells of Rhodococcus R 312 gave the (R)‐1,4‐benzodioxane‐2‐carboxylic acid with high enantioselectivity after 25% conversion. Excellent enantioselectivities for the hydrolysis of both 2‐cyano‐1,4‐benzodioxane as well as 2‐cyano‐6‐formyl‐1,4‐benzodioxane have been achieved and the absolute configuration of 1,4‐benzodioxane‐2‐carboxylic acid was determined to be R by comparison with the specific rotation of commercially available (R)‐1,4‐benzodioxane‐2‐carboxylic acid.

CONCLUSIONS: This new nitrilase‐catalysed kinetic resolution of 2‐cyano‐ and 2‐cyano‐6‐formyl‐1,4‐benzodioxane opens a mild route to optically active 1,4‐benzodioxane‐2‐carboxylic acids. As the formyl functional group would be damaged in chemical nitrile hydrolysis, nitrilase‐catalysed hydrolysis solves this synthetic bottleneck and advances nitrilase biocatalytic tools for the preparation of more complex 1,4‐benzodioxane‐2‐carboxylic acids. Copyright © 2007 Society of Chemical Industry
Changes in tissue free amino acid contents, branchial Na+/K+‐ATPase activity and bimodal breathing pattern in the freshwater climbing perch, Anabas testudineus (Bloch), during seawater acclimation
Authors: Chang Esther Wei Yin , Loong Ai May , Wong Wai Peng , Chew Shit Fun , Wilson Jonathan M. , Ip Yuen Kwong
Published: October 2007

This study aimed to examine effects of short‐ or long‐term acclimation to brackish water or seawater on the climbing perch, Anabas testudineus, which is an aquatic air‐breathing teleost living typically in freshwater. A. testudineus exhibits hypoosmotic and hypoinoic osmoregulation; the plasma osmolality, [Na+] and [Cl−] of fish acclimated to seawater were consistently lower than those of the external medium. However, during short‐term (1 day) exposure to brackish water (15‰) or seawater (30‰), these three parameters increased significantly. There were also significant increases in tissue ammonia and urea contents, contents of certain free amino acids (FAAs) in the muscle, and rates of ammonia and urea excretion in the experimental fish. The accumulated FAAs might have a transient role in cell volume regulation. In addition, these results indicate that increases in protein degradation and amino acid catabolism had occurred, possibly providing energy for the osmoregulatory acclimation of the gills in fish exposed to salinity stress. Indeed, there was a significant increase in the branchial Na+/K+‐ATPase activity in fish exposed to seawater for a prolonged period (7 days), and the plasma osmolality, [Na+] and [Cl−] and the tissue FAA contents of these fish returned to control levels. More importantly, there was a significant increase in the dependence on water‐breathing in fish acclimated to seawater for 7 days. This suggests for the first time that A. testudineus could alter its bimodal breathing pattern to facilitate the functioning of branchial Na+/K+‐ATPase for osmoregulatory purposes. J. Exp. Zool. 307A:708–723, 2007. © 2007 Wiley‐Liss, Inc.
Enhanced transduction of dendritic cells by FcγRI‐targeted adenovirus vectors
Authors: Sapinoro Ramil , Maguire Casey A. , Burgess Angela , Dewhurst Stephen
Published: October 2007

Background

The high affinity Fcγ receptor I (FcγRI; aka CD64) is expressed by dendritic cells (DC) and antigens targeted to this receptor elicit enhanced immune responses. This study was designed to test the hypothesis that targeting an adenoviral (Ad) vector to FcγRI would lead to enhanced transduction of DC and an improved immune response to vector‐encoded antigens.

Methods

A bispecific adaptor molecule consisting of a trimeric adenovirus fiber‐binding moiety fused to a single‐chain antibody specific for human FcγRI was generated. Transduction of cultured cells, including human DC, by the FcγRI‐targeted Ad was then evaluated using reporter genes (GFP, luciferase). Immunophenotypic and functional characteristics of vector‐transduced DC were also measured by flow cytometry, cytokine ELISA and mixed lymphocyte reaction (MLR); antigen‐specific stimulation of autologous CD8+ T cells was evaluated using vectors encoding cytomegalovirus (CMV) pp65.

Results

FcγRI‐targeted Ad transduced primary DC with 10–15‐fold greater efficiency than unmodified Ad or Ad vectors complexed to an adaptor protein that targeted an irrelevant receptor. However, FcγRI‐targeting had no effect of Ad‐induced activation of DC, as measured by cytokine release or expression of cell surface activation markers. Finally, FcγRI‐targeting of vectors encoding CMV pp65 resulted in an increase in the activation of antigen‐specific autologous human CD8+ T cells.

Conclusions

FcγRI‐targeting significantly enhances the efficiency of Ad vector‐mediated gene transfer in primary human DC, and results in an improved immune response to a vector‐encoded antigen. Copyright © 2007 John Wiley & Sons, Ltd.
Multiscalet basis in Galerkin's method for solving three‐dimensional electromagnetic integral equations
Authors: Tong M. S.
Published: October 2007

Multiscalets in the multiwavelet family are used as the basis and testing functions in Galerkin's method. Since the multiscalets are orthogonal to their translations under the Sobolev inner product, the resulting Galerkin's method behaves like a collocation method but possesses the ability of derivative tracking for unknown functions in solving integral equations. The former makes the method simple in implementation and the latter allows to use coarse meshes in discretization. These robust features have been demonstrated in solving two‐dimensional (2D) electromagnetic (EM) problems, but have not been exploited in three‐dimensional (3D) scenarios. For 3D problems, the unknown functions in the integral equations are dependent on two coordinate variables. In order to preserve the use of coarse meshes for 3D cases, we realize the omnidirectional derivative tracking by tracking the directional derivatives along two orthogonal directions, or equivalently tracking the gradient. This process yields a nonsquare matrix equation and we use the least‐squares method (LSM) to solve it. Numerical examples show that the multiscalet‐based Galerkin's method is also robust in solving for 3D EM integral equations with a minor cost increase from LSM. Copyright © 2007 John Wiley & Sons, Ltd.
Leadership styles and group organizational citizenship behavior across cultures
Authors: Euwema Martin C. , Wendt Hein , van Emmerik Hetty
Published: October 2007

This study investigates (a) the effects of societal culture on group organizational citizenship behavior (GOCB), and (b) the moderating role of culture on the relationship between directive and supportive leadership and GOCB. Data were collected from 20 336 managers and 95 893 corresponding team members in 33 countries. Multi‐level analysis was used to test the hypotheses, and culture was operationalized using two dimensions of Hofstede (2001) and GLOBE (2004): Individualism (IDV) and power distance (PD). There was no direct relationship between these cultural dimensions and GOCB. Directive leadership had a negative relation, and supportive leadership a positive relation with GOCB. Culture moderated this relationship: Directive leadership was more negatively, and supportive behavior less positively, related to GOCB in individualistic compared to collectivistic societies. The moderating effects of societal PD were explained by societal IDV. Copyright © 2007 John Wiley & Sons, Ltd.
Comparative study of general purpose synthetic aviation lubricants in regard to wear performance, corrosion prevention and salt water resistance
Authors: Akin Kevin D. , Gschwender Lois , Snyder Carl E. , Franco George
Published: October 2007

MIL‐PRF‐81322 has been used for many years as a wide‐temperature (−54 to 177 °C) aviation lubricant. Recently, MIL‐PRF‐32014 has shown improvement with enhanced wear and corrosion resistance. Various military aircraft component testing will be discussed, both bench and field. A lubricant comparison will be presented, focusing on wear and corrosion testing.

As an additional (and novel) test approach, ASTM D1264, known as water washout, was modified to include synthetic sea water. While there are various lubricant bearing tests for corrosion, none measures a lubricant's resistance to sea water. It is expected to combine corrosion and washout measurements in this test. For many military applications, this property may be helpful in determining the life of the component, as the ability of the grease to remain in place will insure sufficient lubrication as well as corrosion protection. Copyright © 2007 John Wiley & Sons, Ltd.
Analysis of microcystins by capillary high performance liquid chromatography using a polymethacrylate‐based monolithic column
Authors: Gu Congying , Lin Li , Chen Xiaodong , Jia Jinping , Wu Dan , Fang Nenghu
Published: October 2007

A polymethacrylate‐based monolithic column was prepared and its application to the separation of three kinds of similar microcystins (MCs) in capillary high performance liquid chromatography (capillary‐HPLC) with ultraviolet detection was studied. The monolithic matrix contains both hydrophobic and cation‐exchange interaction sites. Factors influencing the separation performance have been investigated. A baseline separation could be achieved by means of Tris(hydroxymethyl)aminomethane buffer of mildly alkaline pH and acetonitrile as the mobile phases in less than 5 min. The calibration curves were linear with a correlation coefficient r >0.9990 over a range of 0.25–18.00 mg/L. This method was successfully applied to the separation of microcystins from other compounds in spiked uncontaminated lake water after performing solid‐phase extraction. The whole procedure provided low LODs, e. g. the LODs for MC‐LR, MC‐YR, and MC‐RR were found to be 0.49, 0.67, 0.30 μg/L, respectively. The LODs, precision, efficiency, and the results obtained for the real samples demonstrate the potential of polymethacrylate‐based monolithic columns as fast separation tools for routine use in the monitoring of microcystins in real water samples.
On‐line solid‐phase extraction with a monolithic weak cation‐exchange column and simultaneous screening of α1‐adrenergic receptor antagonists in human plasma
Authors: Wei Xiaoyi , Yin Junfa , Yang Gengliang , He Chunxia , Chen Yi
Published: October 2007

An on‐line SPE–HPLC method, using a monolithic poly(glycidyl methacrylate‐co‐ethylene glycol dimethacrylate) (poly(GMA‐EDMA)) based weak cation‐exchange (WCX) column, was developed for simultaneous determination of α1‐adrenergic receptor antagonists in human plasma. The monolithic WCX column was prepared by an in‐situ polymerization protocol and modified stepwise with ethylenediamine and chloroacetic acid. On connecting this column to an injection valve, an on‐line SPE protocol could be established for removal of matrices (mainly proteins and lipids) and preconcentration of four α1‐adrenergic receptor antagonists in human plasma. This method was validated and then used for determination of terazosin, alfuzosin, prazosin, and doxazosin in clinical plasma samples. For all analytes, each calibration curve was found to be linear over a range of 0.005–5 μg/mL (R >0.997), and the limit of detection for each analyte was 0.5 ng/mL. Recovery (> 80%) and precision (RSD <15%) for inter‐ and intra‐day assay were tested at three concentration levels of each analyte and showed acceptable results for quantitative assay. Real samples from hypertensive patients were monitored and results were in agreement with those of the conventional liquid–liquid extraction‐HPLC method. Furthermore, due to its good permeability and biocompatibility, the monolithic WCX sorbent could be reused more than 300 times. The proposed method was especially appropriate for multi‐analyte monitoring in plasma samples.