- Covalent inhibition of bacterial quorum sensing
-
Chemical coordination of gene expression among bacteria as a function of population density is regulated by a mechanism known as 'quorum sensing' (QS). QS in Pseudomonas aeruginosa, an opportunistic pathogen that causes disease in immunocompromised patients, is mediated by binding of the transcriptional activator, LasR, to its ligand, 3-oxo-C12-HSL, leading to population-wide secretion of virulence factors and biofilm formation. We have targeted QS in P. aeruginosa with a set of electrophilic probes designed to covalently bind Cys79 in the LasR binding pocket, leading to specific inhibition of QS-regulated gene expression and concomitant reduction of virulence factor secretion and biofilm formation. This first example of covalent modification of a QS receptor provides a new tool to study molecular mechanisms of bacterial group behavior and could lead to new strategies for targeting bacterial virulence.
- Amara, Neri,Mashiach, Roi,Amar, Dotan,Krief, Pnina,Spieser, Stephane A. H.,Bottomley, Matthew J.,Aharoni, Amir,Meijler, Michael M.
-
-
Read Online
- Reversible photo-responsive vesicle based on the complexation between an azobenzene containing molecule and α-cyclodextrin
-
An amphiphilic molecule (Azo-Cl) was successfully synthesized and found to be able to construct reversible spherical vesicles in water. The assembled vesicles disappeared on the addition of equimolar α-cyclodextrin (α-CD) and reformed with UV irradiation
- Liu, Jianjia,Yan, Liang,Wang, Jie,Li, Tao,Zhao, Hanqing,Li, Li,Lincoln, Stephen F.,Prud'homme, Robert K.,Guo, Xuhong
-
-
Read Online
- Polyanion inhibitors of human immunodeficiency virus and other viruses. 5. Telomerized anionic surfactants derived from amino acids
-
ω-Acryloyl anionic surfactants, whose polar heads are derived from amino acids, have been telomerized to prepare polyanions of a predetermined molecular weight. The main goal of this study was to verify whether the antiviral activity is influenced by the degree of polymerization of the polyanions. The oligomeric polyanions were evaluated for their activity against human immunodeficiency virus (HIV-1 or HIV-2) and various other RNA and DNA viruses. With regard to their anti-HIV activity, a minimum number of anionic groups was necessary to achieve an inhibitory effect. Moreover, to be active the overall conformation of the polyanion must be such that the anionic groups are located on the external site of the molecule. With some of the polyanions, a 50% inhibition concentration (IC50) as low as 1 μg/mL, or even 0.1 μg/mL, was noted against HIV-1 in CEM-4 and MT-4 cells, respectively. The most potent polyanions also proved active against human cytomegalovirus and herpex simplex virus at concentrations of 5-10 and 20-40 μg/mL, respectively. No activity was observed against any of the other viruses tested (i.e., vesicular stomatitis, Sindbis, Semliki forest, parainfluenza, Junin, Tacaribe, Coxsackie, polio, reo, and vaccinia). No toxicity for the host cells was observed at concentrations up to 200 μg/mL.
- Leydet, Alain,Barragan, Véronique,Boyer, Bernard,Montéro, Jean Louis,Roque, Jean Pierre,Witvrouw, Myriam,Este, José,Snoeck, Robert,Andrei, Graciela,De Clercq, Erick
-
-
Read Online
- The Synthesis of a Glucosyldiglyceride for Constructing pH-Sensitive Liposomes
-
A glucosyldiglyceride containing residues of 11-aminoundecanoic acid was synthesized for constructing pH-sensitive liposomes.
- Alshoaibi,Andryushina,Morozova,Serebrennikova
-
-
Read Online
- A Lewis acid-mediated protocol for the protection of aryl amines as their Boc-derivatives
-
A new protocol of protection of poorly reactive aryl amines and functionalized amines with Boc2O in the presence of Zn(ClO 4)2·6H2O as the catalyst is reported. The catalytic action of Zn(ClO4)2·6H2O is specific for the activation of the pyrocarbonates, thus acid sensitive functionalities and stereochemical configurations of the starting materials remain unaltered in the protection process.
- Bartoli, Giuseppe,Bosco, Marcella,Locatelli, Manuela,Marcantoni, Enrico,Massaccesi, Massimo,Melchiorre, Paolo,Sambri, Letizia
-
-
Read Online
- Helicity- and Molecular-Weight-Driven Self-Sorting and Assembly of Helical Polymers towards Two-Dimensional Smectic Architectures and Selectively Adhesive Gels
-
Self-sorting plays a crucial role in living systems such as the selective assembly of DNA and specific folding of proteins. However, the self-sorting of artificial helical polymers such as biomacromolecules has rarely been achieved. In this work, single-h
- Li, Yan-Xiang,Xu, Lei,Kang, Shu-Ming,Zhou, Li,Liu, Na,Wu, Zong-Quan
-
-
Read Online
- Discovery, synthesis of novel fusidic acid derivatives possessed amino-terminal groups at the 3-hydroxyl position with anticancer activity
-
A series of novel fusidic acid (FA) derivatives were synthesized and screened for their in vitro cytotoxicity against the Hela, U87, KBV and MKN45 cancer cell lines. Selected FA derivatives with anti-tumor activity were firstly identified including compound 4, which exhibited good anti-proliferative activity with IC50 values in the range of 1.26–3.57 μM. Further research revealed that compound 4 induced Hela cells to undergo apoptosis by increasing the ratio of the cells in the Sub-G0/G1 phase via decreasing the neo-synthesized proteins in a dose-dependent manner from 1 to 10 μM. Compound 4 also showed good in vivo anti-tumor activity against the xenograft tumor of Hela cells and had no apparent toxicity. This study highlights the advantage of introducing the medium-length amino-terminal groups at the 3-OH position of FA to enhance its anti-tumor activity and suggests that compound 4 provides a starting point for designing more potent derivatives in the future.
- Ni, Jingxuan,Guo, Mengqi,Cao, Yucheng,Lei, Lei,Liu, Kangli,Wang, Binghua,Lu, Fangfang,Zhai, Rong,Gao, Xiangwei,Yan, Chunhong,Wang, Hongbo,Bi, Yi
-
-
Read Online
- Synthesis and antibacterial evaluation of novel 3-substituted ocotillol-type derivatives as leads
-
Due to the rapidly growing bacterial antibiotic-resistance and the scarcity of novel agents in development, bacterial infection is still a global problem. Therefore, new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, are urgently needed. In this paper, a series of antibacterial ocotillol-type C-24 epimers modified from natural 20(S)-protopanaxadiol were synthesized and evaluated for their antibacterial activity. According to the screening results of Gram-positive bacteria (B. subtilis 168 and MRSA USA300) and Gram-negative bacteria (P. aer PAO1 and A. baum ATCC19606) in vitro, the derivatives exhibited good antibacterial activity, particularly against Gram-positive bacteria with an minimum inhibitory concentrations (MIC) value of 2-16 μg/mL. The subsequent synergistic antibacterial assay showed that derivatives 5c and 6c enhanced the susceptibility of B. subtilis 168 and MRSA USA300 to chloramphenicol (CHL) and kanamycin (KAN) (FICI 0.5). Our data showed that ocotillol-type derivatives with long-chain amino acid substituents at C-3 were good leads against antibiotic-resistant pathogens MRSA USA300, which could improve the ability of KAN and CHL to exhibit antibacterial activity at much lower concentrations with reduced toxicity.
- Bi, Yi,Liu, Xian-Xuan,Zhang, Heng-Yuan,Yang, Xiao,Liu, Ze-Yun,Lu, Jing,Lewis, Peter John,Wang, Chong-Zhi,Xu, Jin-Yi,Meng, Qing-Guo,Ma, Cong,Yuan, Chun-Su
-
-
Read Online
- Lipase sensing by naphthalene diimide based fluorescent organic nanoparticles: a solvent induced manifestation of self-assembly
-
The precise control of supramolecular self-assembly is gaining utmost interest for the demanding applications of manifested nano-architecture across the scientific domain. This study delineates the morphological transformation of naphthalene diimide (NDI) derived amphiphiles with varying water content in dimethyl sulfoxide (DMSO) and the selective sensing of lipase using its aggregation-induced emission (AIE) properties. To this end, NDI-based, benzyl alcohol protected alkyl chain (C1, C5, and C10) linked amphiphilic molecules (NDI-1,2,3) were synthesized. Among the synthesized amphiphiles, benzyl ester linked C5 tailored naphthalene diimide (NDI-2) exhibited AIE with an emission maximum at 490 nm in a DMSO-water binary solvent system fromfw= 30% and above water content. The fibrous morphology ofNDI-2atfw= 30% got gradually transformed to spherical aggregated particles along with steady increment in the emission intensity upon increasing the amount of water in DMSO. Atfw= 99% water in DMSO, complete transformation to fluorescent organic nanoparticles (FONPs) was observed. Microscopic and spectroscopic techniques demonstrated the solvent driven morphological transformation and the AIE property ofNDI-2. Moreover, this AIE ofNDI-2FONPs was employed in the selective turn-off sensing of lipase against many other enzymes including esterase, through hydrolysis of a benzyl ester linkage with a limit of detection 10.0 ± 0.8 μg L?1. TheNDI-2FONP also exhibited its lipase sensing efficiencyin vitrousing a human serum sample.
- Chakraborty, Debayan,Sarkar, Deblina,Ghosh, Anup Kumar,Das, Prasanta Kumar
-
p. 2170 - 2180
(2021/03/14)
-
- ORGANIC COMPOSITIONS TO TREAT APOC3-RELATED DISEASES
-
The present disclosure relates to compositions and methods for treating APOC3-related diseases such as: hypertriglyceridemia (e.g., Type V Hypertriglyceridemia), abnormal lipid metabolism, abnormal cholesterol metabolism, atherosclerosis, hyperlipidemia, diabetes, including Type 2 diabetes, obesity, cardiovascular disease, and coronary artery disease, among other disorders relating to abnormal metabolism or otherwise, using a therapeutically effective amount of a RNAi agent to APOC3.
- -
-
Paragraph 00708
(2016/02/26)
-
- FATTY ACIDS AND THEIR USE IN CONJUGATION TO BIOMOLECULES
-
The invention provides a conjugate comprising a biomolecule linked to a fatty acid via a linker wherein the fatty acid has the following Formulae A1, A2 or A3: wherein R1, R2, R3, R4, Ak, n, m and p are defined herein. The invention also relates to a method for manufacturing the conjugate of the invention such as GDF15 conjugate, and its therapeutic uses such as treatment or prevention of metabolic disorders or diseases, type 2 diabetes mellitus, obesity, pancreatitis, dyslipidemia, alcoholic and nonalcoholic fatty liver disease/steatohepatitis and other progressive liver diseases, insulin resistance, hyperinsulinemia, glucose intolerance, hyperglycemia, metabolic syndrome, hypertension, cardiovascular disease, atherosclerosis, peripheral arterial disease, stroke, heart failure, coronary heart disease, diabetic complications (including but not limited to chronic kidney disease), neuropathy, gastroparesis and other metabolic disorders. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.
- -
-
Page/Page column 225; 226
(2016/01/25)
-
- Using N-nitrosodichloroacetamides to conveniently convert linear primary amines into alcohols
-
The reported rearrangement of N-nitrosodichloroacetamides provides a practicalmethod for converting primary amines into primary alcohols. The reaction sequence is operationally simple, requires only a single purification, and is compatible with a number of common functional groups. Mechanistic studies of the nitrosylation and rearrangement reactions illustrate the increased utility of dichloroacetamides compared to various other amides for this transformation.
- Macarthur, Nicholas S.,Wang, Linshu,Mccarthy, Blaine G.,Jakobsche, Charles E.
-
supporting information
p. 2014 - 2021
(2015/08/18)
-
- Peptidomimetic inhibitors of N-myristoyltransferase from human malaria and leishmaniasis parasites
-
N-Myristoyltransferase (NMT) has been shown to be essential in Leishmania and subsequently validated as a drug target in Plasmodium. Herein, we discuss the use of antifungal NMT inhibitors as a basis for inhibitor development resulting in the first sub-micromolar peptidomimetic inhibitors of Plasmodium and Leishmania NMTs. High-resolution structures of these inhibitors with Plasmodium and Leishmania NMTs permit a comparative analysis of binding modes, and provide the first crystal structure evidence for a ternary NMT-Coenzyme A/myristoylated peptide product complex. This journal is
- Olaleye, Tayo O.,Brannigan, James A.,Roberts, Shirley M.,Leatherbarrow, Robin J.,Wilkinson, Anthony J.,Tate, Edward W.
-
supporting information
p. 8132 - 8137
(2015/01/08)
-
- Assembly of naphthalenediimide conjugated peptides: Aggregation induced changes in fluorescence
-
Naphthalenediimide appended peptide based self-assembly was studied. Interestingly, an aggregation induced drastic change in the fluorescence property and gel formation were observed depending on the solvent composition (chloroform:methylcyclohexane) at a fixed concentration of 1.6 mM at room temperature.
- Basak, Shibaji,Nanda, Jayanta,Banerjee, Arindam
-
supporting information
p. 6891 - 6893
(2013/07/26)
-
- Design, synthesis, and pharmacological evaluation of fluorescent and biotinylated antagonists of ρ1 GABAC receptors
-
The ρ1 GABAC receptor is a ligand-gated chloride ion channel that shows promise as a therapeutic target for myopia, sleep disorders, memory and learning facilitation, and anxiety-related disorders. As such, there is a need for molecular probes to understand the role GABA C receptors play in physiological and pathological processes. To date, no labeled (either radioactive or fluorescent) GABAC selective ligand has been developed that can act as a marker for GABAC receptor visualization and localization studies. Herein, we report a series of fluorescent ligands containing different-sized linkers and fluorophores based around (S)-4-ACPBPA [(4-aminocyclopenten-1-yl)-butylphosphinic acid], a selective GABAC antagonist. One of these conjugates, (S)-4-ACPBPA-C5-BODIPY (13), displayed moderate potency (IC50 = 58.61 μM) and selectivity (>100 times) for ρ1 over α1β2γ2L GABAA receptors. These conjugates are novel lead agents for the development of more potent and selective fluorescent probes for studying the localization and function of GABAC receptors in living cells.
- Gavande, Navnath,Kim, Hye-Lim,Doddareddy, Munikumar R.,Johnston, Graham A. R.,Chebib, Mary,Hanrahan, Jane R.
-
supporting information
p. 402 - 407
(2013/06/05)
-
- Design of novel tyrosine-nitrogen mustard hybrid molecules active against uterine, ovarian and breast cancer cell lines
-
L-para-Tyrosine was linked to ortho-hydroxyaniline, meta-hydroxyaniline and para-hydroxyaniline giving three distinct tyrosinamide molecules. The new extended amino acid derivatives were constructed to imitate, in part, the estradiol (E2, the natural female sex hormone) nucleus. The resulting tyrosinamides were then linked to chlorambucil either directly, or via a 5 and 10 carbon atoms spacer chain. This was done in an attempt to target cancerous cells expressing the estrogen receptor alpha (ERα) and to obtain a more specific chemotherapeutic agent. The tyrosinamide-chlorambucil molecules were designed and synthesized in good yields, according to two different approaches. The novel compounds were evaluated for their anticancer efficacy in hormone-dependent and hormone-independent (ER+; MCF-7 and ER-; MDA-MB-231) breast cancer cell lines. Interestingly, the meta-hydroxyphenyl-tyrosinamide- chlorambucil derivatives were more active than the ortho- and para- analogs. The molecules bearing a 5 carbon atoms spacer were selected for additional biological study using a panel of female cancerous cells; breast (ZR-75-1, MDA-MB-436, MDA-MB-468), ovarian (OVCAR-3, A2780) and uterine (Ishikawa, HEC-1A). It was discovered that for breast cancer cells, the new compounds were up to 4.2 times more active than chlorambucil itself.
- Desc?teaux, Caroline,Brasseur, Kevin,Leblanc, Valérie,Parent, Sophie,Asselin, éric,Bérubé, Gervais
-
experimental part
p. 403 - 412
(2012/05/19)
-
- Development and characterization of improved β-lactone-based anti-virulence drugs targeting ClpP
-
Here, we report the synthesis and in depth characterization of a second generation β-lactone derived virulence inhibitors. Based on initial results that emphasized the intriguing possibility to disarm bacteria in their virulence the present study develops
- Zeiler, Evelyn,Korotkov, Vadim S.,Lorenz-Baath, Katrin,B?ttcher, Thomas,Sieber, Stephan A.
-
experimental part
p. 583 - 591
(2012/03/26)
-
- COVALENT INHIBITION OF BACTERIAL QUORUM SENSING
-
Inhibitors of bacterial communication, such as quorum sensing, and method of use and manufacture thereof.
- -
-
Page/Page column 20
(2011/02/24)
-
- ANTICANCER AGENTS BASED ON AMINO ACID DERIVATIVES
-
The present invention provides compounds of formula (I): in which T is L or -A-NH-C(O)-L-; L is -(CH2)n- or -(CH2)p-Z-; A is -(CH2)m- or an alkyl component of a naturally occurring amino acid; R is -CO2R1, -CH2OH, -C(O)NH(hydroxyphenyl) or C(S)NH(hydroxyphenyl); R1 is H or is C1-C12 alkyl; X is -OH, OSO2R2, -Cl, -Br, or -I; R2 is C1-C12 alkyl or -CF3; Z is phenyl or naphthyl; m is an integer having a value of 1 to 20; n is an integer having a value of 1 to 20; and p is an integer having a value of 1 to 20 or an enantiomer, diastereoisomer, racemic mixture, pharmaceutically acceptable salt, solvate or prodrug thereof. These compounds can be useful as anticancer agents.
- -
-
Page/Page column 33
(2011/02/24)
-
- Synthesis of D- and L-tyrosine-chlorambucil analogs active against breast cancer cell lines
-
A series of d- and l-tyrosine-chlorambucil analogs was synthesized as anticancer drugs for chemotherapy of breast cancer. The novel compounds were synthesized in good yields through efficient modifications of d- and l-tyrosine. The newly synthesized compounds were evaluated for their anticancer efficacy in different hormone-dependent and hormone-independent (ER+ and ER-) breast cancer cell lines. The novel analogs showed significant in vitro anticancer activity when compared to chlorambucil. Structure-activity relationship (SAR) reveals both, the influence of the length of the spacer chain and the stereochemistry of the tyrosine moiety. Interestingly, the d- and l-tyrosinol-chlorambucil derivatives with 10 carbon atoms spacer are selective towards MCF-7 (ER+) breast cancer cell line.
- Desc?teaux, Caroline,Leblanc, Valérie,Brasseur, Kevin,Gupta, Atul,Asselin, éric,Bérubé, Gervais
-
scheme or table
p. 7388 - 7392
(2011/02/25)
-
- Enantioselective linchpin catalysis by SOMO catalysis: An approach to the asymmetric a-chlorination of aldehydes and terminal epoxide formation
-
Time for SOme MOre: For the first time SOMO (singly occupied molecular orbital) activation has been exploited to allow a new approach to the α-chlorination of aldehydes. This transformation can be readily implemented as part of a linchpin catalysis approach to the enantioselective production of terminal epoxides.
- Amatore, Muriel,Beeson, Teresa D.,Brown, Sean P.,MacMillan, David W. C.
-
supporting information; experimental part
p. 5121 - 5124
(2009/12/07)
-
- Benzyl and tert-butyl carbamate derivatives of 1,ω-amino acids as simple yet efficient gelators
-
We report the synthesis and a study of the gelation properties of a series of N-protected long-chain amino acids. Especially, benzyl and tert-butyl carbamate derivatives of 11-aminoundecanoic acid in their deprotonated form can gelate polar organic solvents and water at very low concentration (less than 5 mM). This is explained by the contribution of multiple forces-H-bond, van der Waals and ionic interactions-in the gel aggregate formation and stabilization, which is confirmed by the experimental data. Among the series of compounds investigated, only a dimer of 11-aminoundecanoic acid is capable of gelating toluene, which stems from the increased number of hydrogen bonding sites in the main aliphatic chain.
- D'Ale?o, Anthony,Pozzo, Jean-Luc,Heuzé, Karine,V?gtle, Fritz,Fages, Frédéric
-
p. 7482 - 7488
(2008/02/05)
-
- ALIPHATIC AMIDE and ESTER PYRAZINOYLGUANIDINE SODIUM CHANNEL BLOCKERS
-
The present invention relates to sodium channel blockers. The present invention also includes a variety of methods of treatment using these inventive sodium channel blockers.
- -
-
Page/Page column 44
(2008/06/13)
-
- Anti-HIV agents with dual sites of action
-
The present invention provides compounds of the general structure: which are substituted at the 3 and 28 positions, along with pharmaceutical formulations containing the same and methods of treating viral infections employing the same.
- -
-
Page/Page column 6; 15
(2008/06/13)
-
- Chiroptical Switching in a Bistable Molecular Shuttle
-
Although various methods for switching the positions of macrocycles in bistable rotaxane-based molecular shuttles have been developed, exploiting such movements to trigger property changes has thus far received little attention. Here we describe one of th
- Bottari, Giovanni,Leigh, David A.,Perez, Emilio M.
-
p. 13360 - 13361
(2007/10/03)
-
- Amphipatic polycarboxylic chelates and complexes with paramagnetic metals as MRI contrast agents
-
Substituted polycarboxylic ligand molecules and corresponding metal complexes of said ligands, preferably paramagnetic metals complexes for generating responses in the field of magnetic resonance imaging (MRI). The paramagnetic complexes of the polycarboxylic ligands possess advantageous tensioactive properties and are useful as MRI contrast media in formulations for investigating the blood pool.
- -
-
Page column 33-34
(2010/11/29)
-
- Design, synthesis, and pharmacological evaluation of thapsigargin analogues for targeting apoptosis to prostatic cancer cells
-
A series of thapsigargin (TG) analogues, containing an amino acid applicable for conjugation to a peptide specifically cleaved by prostate-specific antigen (PSA), has been prepared to develop the drug-moiety of prodrugs for treatment of prostatic cancer. The analogues were synthesized by converting TG into O-8-debutanoylthapsigargin (DBTG) and esterifying O-8 of DBTG with various amino acid linkers. The compounds were evaluated for their ability to elevate the cytosolic Ca2+ concentration ([Ca2+]i) in TSU-Pr1 cells, their ability to inhibit the rabbit skeletal muscle SERCA pump, and their ability to induce apoptosis in TSU-Pr1 human prostatic cancer cells. The activity of analogues, in which DBTG were esterified with ω-amino acids [HOOC(CH2)nNH2, n = 5-7, 10, 11], increased with the linker length. Analogues with 3-[4-(L-leucinoylamino)phenyl]propanoyl, 6-(L-leucinoylamino)hexanoyl, and 12-(L -serinoylamino)dodecanoyl were considerably less active than TG, and analogues with 12-(L-alaninoylamino)dodecanoyl and 12-(L-phenylalaninoylamino)dodecanoyl were almost as active as TG. The 12-(L-leucinoylamino)dodecanoyl gave an analogue equipotent with TG, making this compound promising as the drug-moiety of a PSA sensitive prodrug of TG.
- Jakobsen,Denmeade,Isaacs,Gady,Olsen,Christensen
-
p. 4696 - 4703
(2007/10/03)
-
- 4,9-ETHANO-BENZO(F)ISOINDOLE DERIVATIVES AS FARNESYL TRANSFERASE INHIBITORS
-
Novel products of formula (I): STR1 preparation thereof and pharmaceutical compositions containing said products are disclosed. In formula (I), R is a group of formula (CH 2) m X 1 (CH 2) n Z, where X 1 is a simple bond or O or S, n is 0 or 1 and n is 0,
- -
-
-
- Lipophilic drug derivatives for use in liposomes
-
The present invention provides novel lipophilic drug derivatives which are capable of being formulated in liposomes or micelles. These drug derivatives are known therapeutic agents which are covalently attached to a fatty acid chain of a phospholipid, glyceride, ceramide or 1,2-diacyloxypropane-3-amine. The linkage between the therapeutic agent and the lipid is one which can be cleaved in vivo, allowing the therapeutic agent to be separated from the micellar or liposomal formulation.
- -
-
-
- Synthesis and Immunoadjuvant Activity of the Conjugates of 1-Thio-N-acetyl-muramoyl Dipeptide with Lipid A Subunit Analogs
-
A variety of immunomodulators were synthesized by combining biologically active derivatives of 1-thio-muramoyl dipeptide with 4-O-phosphono-D-glucosamine derivatives related to bacterial lipid A, and using the (succinoylamino)undecanoyl group.Their immunoadjuvant activities in guinea-pigs were examined.
- Ogawa, Yuji,Kitagawa, Masayuki,Fujishima, Yushun,Kiso, Makoto,Hasegawa, Akira,et al.
-
p. 1025 - 1036
(2007/10/02)
-
