bluuebunny/crossref_metadata_2025 huggingface dataset:
Policies, plans, practice, and prospects: irrigation in northeastern Syria
Authors: Hole F. , Zaitchik B. F.
Published: December 2006

Over the past half‐century the agricultural landscape of northeastern Syria has been transformed, due in large part to the introduction of significant irrigation to the steppe. At the beginning of this period, irrigation was confined almost entirely to river floodplains and natural depressions. The steppe was dominated by wintertime rain‐fed agriculture and year‐round grazing. The introduction of diesel‐powered wells and, subsequently, state‐operated dam and canal systems, has led to the expansion of both wintertime and summertime irrigation on the steppe away from the floodplain. The sustainability of these irrigation projects has always been suspect. Even as technologies for water extraction have allowed for previously impossible patterns of cultivation, the combination of declining water quality, a deepening water‐table, and degradation‐prone soils have limited crop yields and led to the rapid abandonment of many steppe farms. The actual trajectory of land‐use in the region is determined by social and political forces as well as by hydrology and surficial geology. In this paper we examine recent land‐use history in the watersheds of two tributaries of the Euphrates River, the Balikh and Khabur. A review of historical drivers of development in the region is combined with satellite analyses to provide an overview of the structure and dynamics of land‐use in this water‐limited region. Copyright © 2006 John Wiley & Sons, Ltd.
Tellurium‐Based Polymeric Surfactants as a Novel Seleno‐Enzyme Model with High Activity
Authors: Huang Xin , Dong Zeyuan , Liu Junqiu , Mao Shizhong , Luo Guimin , Shen Jiacong
Published: December 2006

Summary: A tellurium‐based polymeric sufactant as a seleno‐enzyme model has been constructed by employing 11‐acryloyloxyundecyltriethylammonium bromide (AUTEAB, 4) and a tellurium‐containing compound (1). It demonstrates strong substrate binding ability for thiols and high glutathione peroxidase (GPx) activity about 6 orders of magnitude more efficient than the well‐known GPx mimic PhSeSePh in an ArSH assay system. More importantly, a series of tellurium‐based polymeric micelle catalysts with the catalytic tellurium center located at various positions in the micelle have been constructed, and the dramatic difference in activity indicates that the exact match of the catalytic center and binding site plays a key role in enzyme catalytic efficiency.

Schematic representation of the proposed mode of the telluro‐micelle catalysts.

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Schematic representation of the proposed mode of the telluro‐micelle catalysts.
Oxidative Polymerization of Silylthioketene Dimer
Authors: Naka Kensuke , Inagi Shinsuke , Chujo Yoshiki
Published: December 2006

Summary: The first π‐conjugated poly(thioketene dimer) was synthesized via the homopolymerization of a silylthioketene dimer by a chemical oxidation‐reduction process. The polymerization of trimethylsilylthioketene dimer in the presence of FeCl3 (in CHCl3 at 70 °C for 24 h) gave the corresponding doped poly(thioketene dimer). After treatment of the doped polymer with an aqueous solution of ammonia, the neutral poly(thioketene dimer) was obtained with an incidental desilylation. The polymer obtained was soluble in DMF and DMSO. From gel permeation chromatographic analysis (DMF, polystyrene standards), the number‐average molecular weight of the polymer was found to be 7 460. The polymer showed low oxidation potentials derived from the thioketene dimer unit. An effective extension of the π‐conjugation was observed in the polymer.

Synthesis of π‐conjugated poly(thioketene dimer).

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Synthesis of π‐conjugated poly(thioketene dimer).
Synthesis and Characterization of a Novel Thermo‐Sensitive Copolymer of N‐Isopropylacrylamide and Dibenzo‐18‐crown‐6‐diacrylamide
Authors: Ju Xiao‐Jie , Chu Liang‐Yin , Mi Peng , Song Hang , Lee Yong Moo
Published: December 2006

Summary: A series of novel, thermo‐sensitive copolymers with different molar ratios of N‐isopropylacrylamide (NIPAM) and hydrophobic cis‐dibenzo‐18‐crown‐6‐diacrylamide (cis‐DBCAm) were prepared via free‐radical copolymerization. cis‐DBCAm with polymerizable end groups was successfully synthesized by reacting the corresponding amino crown ether with acryloyl chloride. The copolymers were characterized by FT‐IR and elemental analysis, and the thermo‐sensitivities of the copolymers were evaluated by measuring their lower critical solution temperatures (LCSTs) in the absence or presence of various metal ions. The results indicated that incorporation of cis‐DBCAm lowered LCSTs, and that the LCSTs of the copolymers decreased with the increase in cis‐DBCAm content in the copolymers. When the cavities of the crown ether units captured either K+ or Cs+ ions, the LCST of the respective copolymer–metal ion complex was further decreased, whereas the capture of Na+ or Li+ ions did not have a significant influence on the LCSTs of the copolymers.

Incorporation of cis‐DBCAm into PNIPAM resulted in a lower LCST. The LCST was decreased more when the cavities of the crown ether units captured K+ ions.

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Incorporation of cis‐DBCAm into PNIPAM resulted in a lower LCST. The LCST was decreased more when the cavities of the crown ether units captured K+ ions.
Short bouts of stretching increase myo‐D, myostatin and atrogin‐1 in rat soleus muscle
Authors: Peviani Sabrina Messa , Gomes Anna Raquel Silveira , Moreira Roberta Fátima Carreira , Moriscot Anselmo Sigari , Salvini Tania Fátima
Published: December 2006

Stretching is widely used in rehabilitation and sports activities to improve joint range‐of‐motion and flexibility in humans, but the effect of stretching on the gene expression of skeletal muscle is poorly understood. We evaluated the effect of short bouts of passive stretching of rat soleus muscle on myo‐D, myostatin, and atrogin‐1 gene expressions. Six groups of animals were submitted to a single session of stretching (10 stretches of 1 minute with 30 seconds of rest between them, performed manually) and were evaluated immediately (I), and 8, 24, 48, 72, and 168 hours after the session. To evaluate the effect of repetitive sessions of stretching on the soleus muscle over 1 week, three groups of animals received a single session per day of stretching and the muscle was evaluated immediately after 2, 3, and 7 sessions. The mRNA levels of myo‐D, myostatin, and atrogin‐1 were determined by real‐time polymerase chain reaction. A single session of stretching increased the mRNA levels of myo‐D (after 24 h), myostatin (I, and 168 h later), and atrogin‐1 (after 48 h). Repeated daily session of stretching over 1 week increased myostatin (after 7 sessions) and atrogin‐1 expression (after 2, 3, and 7 sessions). Thus, short bouts of passive stretching are able to increase the gene expression of factors associated with muscle growth (myo‐D), negative regulation of muscle mass (myostatin), and atrophy (atrogin‐1), indicating muscle remodeling through different pathways. Muscle Nerve, 2006
New mutation of the MPZ gene in a family with the Dejerine–Sottas disease phenotype
Authors: Floroskufi Paraskewi , Panas Marios , Karadima Georgia , Vassilopoulos Demetris
Published: December 2006

Charcot–Marie–Tooth disease type 1B is associated with mutations in the myelin protein zero gene. In the present study a new myelin protein zero gene mutation (c.89T>C,Ile30Thr) was detected in a family with the Dejerine–Sottas disease phenotype. The results support the hypothesis that severe, early‐onset neuropathy may be related to either an alteration of a conserved amino acid or a disruption of the tertiary structure of myelin protein zero. Muscle Nerve, 2006
Tandem duplication of DMD exon 18 associated with epilepsy, macroglossia, and endocrinologic abnormalities
Authors: Weiss Claudia , Jakubiczka Sibylle , Huebner Angela , Klopocki Eva , Kress Wolfram , Voit Thomas , Hübner Christoph , Schuelke Markus
Published: December 2006

We describe a patient with Duchenne muscular dystrophy (DMD) who additionally suffered from intractable seizures, severe mental retardation, and a marked macroglossia. He also had endocrinologic abnormalities consisting of growth hormone deficiency, delayed puberty, and adrenal hypoplasia. We detected a duplication of DMD exon 18 and flanking introns that caused a frame‐shift and was not removed by corrective splicing. A coincident mutation in the FKRP gene was excluded by direct sequencing. Complex DNA rearrangements, deletions, and duplications >100 kb were excluded through microarray–comparative genomic hybridization (CGH), although we were not able to exclude a second coincident mutation with certainty. In conclusion, we present a case of DMD that conflicts with current understanding of genotype–phenotype relations and discuss putative pathogenetic mechanisms for this uncommon phenotype. Muscle Nerve, 2006
Calculation of denominator functions for nonstandard finite difference schemes for differential equations satisfying a positivity condition
Authors: Mickens Ronald E.
Published: December 2006

An essential feature of nonstandard finite difference schemes for differential equations is the precise manner in which the discretization of derivatives is made. We demonstrate, for differential equations modeling systems where the solutions satisfy a positivity condition, that procedures can be formulated to calculate the so‐called denominator functions that appear in the discrete derivatives. These procedures are applied to a number of both ordinary and partial model differential equations to illustrate their use. © 2006 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 2007
Inverse microemulsion copolymerization of butyl acrylate and acrylamide: kinetics, colloidal parameters and some model applications
Authors: Yildiz Ufuk , Capek Ignác , Berek Dušan , Sarov Yanko , Rangelow Ivo W
Published: December 2006

The inverse microemulsion copolymerization of acrylamide and butyl acrylate initiated by ammonium peroxodisulphate, a water‐soluble initiator, and stabilized by anionic emulsifiers sodium bis‐2‐ethylhexylsulfosuccinate and sodium dodecylsulphate (SDS) has been studied. An increase of SDS concentration was observed to increase both the rate of polymerization and the particle size. The average number of radicals per particle (n̄) is much below 0.5, which indicates desorption of monomeric radicals from polymer particles. The exit (desorption) rate constants k′des (cm2 s−1) and kdes (s−1) were evaluated as a function of SDS concentration (or the particle size) according to the Ugelstad/O'Toole (I), Nomura (II) and Gilbert (III) models. The value of kdes (s−1) decreases with increasing particle size (or SDS concentration) for all three (I, II and III) models. A complex trend appears for k′des (cm2 s−1): the Ugelstad/O'Toole model estimates a decrease, the Nomura model finds no variation and the Gilbert model estimates even a slight increase in k′des with increasing SDS concentration. Copyright © 2006 Society of Chemical Industry
Miscibility and mechanical properties of an amine‐cured epoxy resin blended with poly(ethylene oxide)
Authors: Larrañaga Maider , Mondragon Iñaki , Riccardi Carmen Cristina
Published: December 2006

Blends composed of diaminodiphenylmethane bisphenol‐A epoxy resin and poly(ethylene oxide) (PEO) were prepared via in situ curing reaction of epoxy in the presence of PEO. The miscibility of the blends before and after curing was established by thermal (differential scanning calorimetry, DSC), microstructural (atomic force microscopy) and dynamic mechanical analysis. Fourier transform infrared spectroscopy indicated that the OH groups developed through cure reactions interact by hydrogen bonding with PEO. After crystallinity analysis by DSC, the interaction parameter was determined through the depression of the equilibrium melting temperature. Mechanical properties of the miscible blends do not show any significant change, although improvement of fracture toughness has been observed with respect to the matrix properties. Copyright © 2006 Society of Chemical Industry
Effect of annealing on the microphase separated behavior and properties of PDMS–MDI–PEG multiblock copolymer films
Authors: Fang Hongxia , Feng Libang , You Bo , Wu Limin
Published: December 2006

A model multiblock copolymer based on (Poly dimethylsiloxane) (PDMS),–4, 4′‐diphenylmethanediisocyanate (MDI)–(poly ethylene glycol) (PEG) was synthesized by employing two step growth polymerization technique. The effect of annealing on microphase separation of the copolymer surface and bulk, surface composition, hydrogen‐bonding and some properties was investigated by AFM, SAXS, XPS, FTIR, contact angle measurement, and protein adsorption experiment, respectively. It was found that increasing the annealing temperature availed formation of microphase separation and surface enrichment of PDMS, which was accompanied by increase in average interdomain spacing, long period, and the crystallizing degree in the hard domains. But the best microphase separated structure seemed to occur at the annealing temperature of 140 °C; exorbitant annealing temperature might demolish the ordered structure. The annealing temperature dependence of microphase separation was further confirmed by the changes in urea hydrogen‐bonding and melting points characterized by FTIR and DSC, respectively. Protein adsorption experiments revealed that all annealed copolymer films possessed the low protein adsorption. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 208–217, 2007
Higher order structural analysis of stereocomplex‐type poly(lactic acid) melt‐spun fibers
Authors: Furuhashi Yukiko , Kimura Yoshiharu , Yamane Hideki
Published: December 2006

The higher order structure of stereocomplex‐type poly(lactic acid) melt‐spun fibers of an equimolar blend of poly(L‐lactic acid) and poly(D‐lactic acid) was analyzed with wide‐angle X‐ray diffraction (WAXD) and birefringence measurements. Two different crystalline structures were observed in the fibers: α‐form homocrystals and stereocomplex crystals. The weight fractions of the two crystals were estimated with the WAXD integrated intensity data. The crystalline orientation factors were obtained from the WAXD measurements. Well‐oriented homocrystals formed during a drawing process at the crystallization temperature of the homocrystal. Drawing above this temperature caused the stereocomplex crystal to be formed. The crystalline orientation tended to be lower with increasing drawing temperatures. Through the combination of the intrinsic birefringence and the fractions of the α‐form homocrystals and stereocomplex crystals, the birefringence of the amorphous phase was evaluated. The amorphous birefringence stayed positive and decreased with increasing drawing temperature. © 2006 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 218–228, 2007
A knowledge‐based move set for protein folding
Authors: Chen William W. , Yang Jae Shick , Shakhnovich Eugene I.
Published: December 2006

The free energy landscape of protein folding is rugged, occasionally characterized by compact, intermediate states of low free energy. In computational folding, this landscape leads to trapped, compact states with incorrect secondary structure. We devised a residue‐specific, protein backbone move set for efficient sampling of protein‐like conformations in computational folding simulations. The move set is based on the selection of a small set of backbone dihedral angles, derived from clustering dihedral angles sampled from experimental structures. We show in both simulated annealing and replica exchange Monte Carlo (REMC) simulations that the knowledge‐based move set, when compared with a conventional move set, shows statistically significant improved ability at overcoming kinetic barriers, reaching deeper energy minima, and achieving correspondingly lower RMSDs to native structures. The new move set is also more efficient, being able to reach low energy states considerably faster. Use of this move set in determining the energy minimum state and for calculating thermodynamic quantities is discussed. Proteins 2007. © 2006 Wiley‐Liss, Inc.
Impurity‐related optical properties in rectangular‐transverse section GaAs–Ga1–xAlxAs quantum well wires: Hydrostatic pressure and electric field effects
Authors: González J. W. , López S. Y. , Rodríguez A. H. , Porras‐Montenegro N. , Duque C. A.
Published: December 2006

Using a variational procedure within the effective mass approximation, we have calculated the influence of an applied electric field and hydrostatic pressure on the shallow‐impurity‐related optical properties in a rectangular‐transverse section GaAs–Ga1–x Alx As quantum well wire. The electric field is applied in the plane of the transverse section of the wire and different angular directions have been considered. The results presented are for the impurity binding energy, its corresponding density of impurity states, and impurity‐related transition energy and polarizability. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On the ductile response dependence upon phase transformation in diamond turning of semiconductors
Authors: Jasinevicius R. G. , Pizani P. S.
Published: December 2006

It is well established that during machining, materials with lower hardness presents higher ductility. However, in the machining of semiconductor crystals the brittle to ductile transition may not strictly follow this rule. This paper intends to show that the extent of the ductile response of monocrystalline semiconductors can not be related to its microhardness value, since the plastic behavior of semiconductor crystals is related to a phase transformation induced by pressure/stress. This was investigated by carrying out microindentation and single point diamond turning tests in three different semiconductors, InSb, GaAs and Si[001]‐oriented single crystals. Based upon tests results it is observed that the onset of brittle behavior is brought forward to semiconductors with higher transition pressure value. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
High‐pressure X‐ray diffraction study of ternary and non‐stoichiometric PbTe and PbSe crystals
Authors: Ovsyannikov Sergey V. , Shchennikov Vladimir V. , Manakov Andrey Y. , Likhacheva Anna Y. , Berger Ivan F. , Ancharov Alexey I. , Sheromov Mikhail A.
Published: December 2006

The paper reports the pressure‐induced phase transitions observed in ternary PbTe and PbSe compounds (Pb1–x Snx Te, Pb1–x Mnx Te, Pb1–x Snx Se) and non‐stoichiometric PbTe ones (Pb0.55Te0.45, Pb0.45Te0.55) at room temperature in the range of 0 to14 GPa by means of angle‐dispersive X‐ray diffraction (ADXRD). The structure of the intermediate high‐pressure phase appearing above ∼6 GPa for all PbTe‐based compounds was established to be Pnma (orthorhombic), like in binary PbTe. The patterns of the intermediate high‐pressure phase of Pb1–x Snx Se (x = 0.125) were found to correspond entirely neither to GeS nor to orthorhombic Pnma, but the calculated reflections for GeS type were closer to the experimental ones. A model of the phase transformations is discussed. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Post‐spinel transition and magnetic properties of LiMn2O4
Authors: Yamaura K. , Huang Q. , Zhang L. , Takada K. , Baba Y. , Nagai T. , Matsui Y. , Kosuda K. , Takayama‐Muromachi E.
Published: December 2006

A post spinel transition of LiMn2O4 was recently found at 6 GPa. The high‐pressure form crystallizes into a double chain‐type structure, isostructural with CaFe2O4 (orthorhombic; Pnma). The orthorhombic unit cell parameters were found anisotropically dependent on the heating condition; it varies ∼0.5% while less than ∼0.1% along the chain direction, probably reflecting nature of the anisotropic structure basis. The form is magnetic due to the chain arrangement of the Mn magnetic moments and a magnetically glassy feature was found at ∼10 K being similar with what was found for the spinel‐type LiMn2O4 at ∼25 K. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Random cubic planar graphs
Authors: Bodirsky Manuel , Kang Mihyun , Löffler Mike , McDiarmid Colin
Published: December 2006

We show that the number of labeled cubic planar graphs on n vertices with n even is asymptotically αn−7/2ρ−nn!, where ρ−1 ≐ 3.13259 and α are analytic constants. We show also that the chromatic number of a random cubic planar graph that is chosen uniformly at random among all the labeled cubic planar graphs on n vertices is three with probability tending to e ≐ 0.999568 and four with probability tending to 1 − e as n → ∞ with n even. The proof given combines generating function techniques with probabilistic arguments. © 2006 Wiley Periodicals, Inc. Random Struct. Alg., 2007
A correlated frailty model with long‐term survivors for estimating the heritability of breast cancer
Authors: Locatelli Isabella , Rosina Alessandro , Lichtenstein Paul , Yashin Anatoli I.
Published: December 2006

The aim of this study is to investigate the role of genetics and environment in susceptibility to breast cancer (frailty). An interdisciplinary approach was adopted, combining a correlated frailty‐mixture model with genetic equations, allowing for decomposition of the frailty variance into genetic and environmental components. In addition, the possibility that a fraction of the population under study is ‘immune’ to the disease is evaluated, and changes in heritability estimates introducing a fraction of non‐susceptible individuals are determined. The methodology is applied to breast cancer data from the Swedish Twin Registry, including information about all female monozygotic and dizygotic twin pairs born in Sweden between 1886 and 1967. The inferential problem is solved in a Bayesian framework and the numerical work is carried out using Markov chain Monte Carlo (MCMC) methods. Copyright © 2006 John Wiley & Sons, Ltd.
Type‐A behavior in a multinational organization: a study of two countries
Authors: Jamal Muhammad
Published: December 2006

This study examined the relationship of global Type A and its components (time pressure and hard driving/competitiveness) with job performance, job satisfaction and health problems among employees working in a multinational company in Malaysia (N = 305) and Pakistan (N = 325).

Data were collected by means of a structured questionnaire from employees concerning Type‐A behavior, job satisfactions and health problems. Job performance data were obtained from the company's personnel files. The immediate supervisor provided the job performance rating annually for all employees. Bivariate multiple regressions were used to analyze the data. Global Type A and its two components were not related to job performance in either countries. Global Type A and the components time pressure and hard driving/competitiveness were significantly related to job satisfaction and health problems in both countries. Some support for the differential effects of Type‐A behavior components on health problems was noted in both samples. Implications of findings are discussed for international and cross‐cultural research. Copyright © 2006 John Wiley & Sons, Ltd.
Biosynthesis and biotransformation of ether lipids
Authors: Mangold Helmut K. , Weber Nikolaus
Published: December 2006

Some naturally occurring as well as synthetic ether lipids are biologically active. In certain cases, the effects of these substances are enhanced, in others, they are inhibited by compounds that were isolated from natural sources or prepared by chemical synthesis. The biotrans‐formation of natural or “unnatural” ether lipids in microorganisms, plant or animal tissue also can lead to substances that elicit biological effects. The production of such compounds through various biotechnological techniques is a field wide open for future exploration. In addition to animal cell cultures, plant cell cultures may become useful tools in biomedical studies concerned with ether lipids.
The degradation of platelet‐activating factor and related lipids: Susceptibility to phospholipases C and D
Authors: Wilcox Rebecca W. , Wykle Robert L. , Schmitt Jeffery D. , Daniel Larry W.
Published: December 2006

1‐O‐Octadecyl‐2‐O‐methyl‐rac‐glycero‐3‐phosphocholine (ET‐18‐OCH3) is an ether‐linked lipid that exhibits selective cytotoxicity toward several types of tumor cells and is relatively inactive toward normal cells under the same conditions of treatment. The mechanism of this selective cytotoxicity is unknown. We conducted studies to determine whether this compound is metabolized by phospholipases C and D and, if so, whether sensitive and resistant cells differ in their ability to degrade ET‐18‐OCH3 by these enzymes. We have examined the metabolism of the L‐isomer of ET‐18‐OCH3, 1‐O‐octadecyl‐2‐O‐methyl‐sn‐glycero‐3‐phosphocholine (L‐ET‐18‐OCH3), by lysophospholipase D of rat liver microsomes and by a phospholipase D from the marine bacteriumVibrio damsela. The metabolism of L‐ET‐18‐OCH3 was also examined in cell culture using Madin‐Darby canine kidney cells, human promyelocytic leukemia cells and human myelocytic leukemia cells. In these studies, L‐ET‐18‐OCH3 and related 1‐O‐alkyl‐linked phosphocholine analogs radiolabeled with3H in the 1‐O‐alkyl chain were used.

L‐ET‐18‐OCH3 was not hydrolyzed by lysophospholipase D from rat liver microsomes under conditions where cleavage of 1‐O‐alkyl‐2‐lyso‐sn‐glycero‐3‐phosphocholine was observed. However, phospholipase D from the marine bacteriumV. damsela readily hydrolyzed L‐ET‐18‐OCH3 to 1‐O‐[3H]octadecyl‐2‐O‐methyl‐sn‐glycero‐3‐phosphate, demonstrating that L‐ET‐18‐OCH3 can be degraded by a phospholipase D. Platelet‐activating factor (PAF) and lyso‐PAF were also substrates for the bacterial phospholipase D.

When intact cells were incubated with radiolabeled L‐ET‐18‐OCH3 a product was formed that was identified as 1‐O‐[3H]octadecyl‐2‐O‐methyl‐sn‐glycerol. There are two mechanisms that could account for the appearance of this product. The first involves cleavage of the compound by a phospholipase C, resulting in direct release of the diglyceride. The second possible mechanism involves cleavage by a phospholipase D to form the phosphatidic acid analog with subsequent hydrolysis to the diglyceride by a phosphohydrolase. Preliminary data support the phospholipase C‐type mechanism. Regardless of which mechanism operates in intact cells, the metabolic degradation of L‐ET‐18‐OCH3 does not appear to be a significant factor in the selective cytotoxicity of this antitumor agent.
Increased membrane permeability for an antitumoral alkyl lysophospholipid in sensitive tumor cells
Authors: Storch Joachim , Munder Paul G.
Published: December 2006

We have investigated cellular sensitivity to the antitumoral alkyl lysophospholipid (ALP) 1‐O‐octadecyl‐2‐O‐methyl‐rac‐glycero‐3‐phosphocholine (ET‐18‐OCH3) in vitro. The permeation of this lipid into the cell was not influenced by metabolic inhibitors of ATP biosynthesis. ET‐18‐OCH3 uptake was not saturable within sublytic concentrations, but could be inhibited in part by cytochalasin B (CB) and dipyridamole. The activation energy of the CB‐sensitive uptake process was increased up to threefold compared to CB‐insensitive uptake. ET‐18‐OCH3 influx and equilibrium binding of ET‐18‐OCH3 were decreased in a fibrosarcoma cell variant (MethA) selected for ET‐18‐OCH3 resistance. The resistant MethA cells were also less sensitive to cytolysis by lysophosphatidylcholine and other ALP. After 72 hr, the resistant MethA cells had metabolized only 11.8% more of the absorbed ET‐18‐OCH3 than sensitive MethA cells. However, they tolerated at least a 30‐fold concentration of this ALP. The uptake mechanism, which could be inhibited by CB, was less active in resistant MethA cells and several other ALP‐resistant cell lines. The concentration of CB, required for maximal uptake inhibition, was increased more than four times in the ALP‐sensitive tumor cell lines. CB‐specific ET‐18‐OCH3 uptake was also enhanced after virus transformation of 3T3 fibroblasts by SV 40. Dipyridamole retarded the ET‐18‐OCH3‐mediated cell destruction.
Accumulation of an alkyl lysophospholipid in tumor cell membranes affects membrane fluidity and tumor cell invasion
Authors: van Blitterswijk Wim J. , Hilkmann Henk , Storme Guy A.
Published: December 2006

Tumor cells grown in the presence of 1‐O‐alkyl‐2‐O‐methylglycero‐3‐phosphocholine (AMG‐PC) accumulated this ether lipid in their membranes. Depending on the cell type and the dose of the compound, up to 17% of the total phospholipids of the purified plasma membranes consisted of authentic AMG‐PC. Extensive incorporation of the agent resulted in a decrease in plasma membrane fluidity and inhibition of tumor cell invasiveness in embryonic chick heart fragments. The extent of AMG‐PC incorporation and fluidity change was not strictly correlated with the degree to which tumor cell invasion was inhibited.
Substrate specificity ofO‐alkylglycerol monooxygenase (E.C. 1.14.16.5), solubilized from rat liver microsomes
Authors: Kötting Jochem , Unger Clemens , Eibl Hansjörg
Published: December 2006

Synthetic alkyl lysophospholipids (ALP) show antineoplastic activity. In the present discussion, the cytotoxicity of ALP is attributed to their accumulation in tumor cells. Some neoplastic cell species, in contrast to normal cells, cannot metabolize ALP because of a lack ofO‐alkylglycerol monooxygenase (AGMO) activity. To understand the metabolic fate of ether lipids and etherlinked phospholipids, AGMO substrate specificity studies were undertaken. Thirty‐five different natural and synthetic ether lipids and their metabolites (including a thioether) were tested as substrates for AGMO. The study revealed that the potent cytostatic substance, 1‐O‐octadecyl‐2‐O‐methyl‐rac‐glycero‐3‐phosphocholine is not a substrate for AGMO. Therefore, its selective toxicity to tumor cells cannot be based on the differences in direct detoxification of 1‐O‐octadecyl‐2‐O‐methyl‐rac‐glycero‐3‐phosphocholine by AGMO in normal and malignant cells. However, 1‐O‐octadeyl‐2‐O‐methyl‐rac‐glycerol, which can be formed by phospholipase C hydrolysis, is a good substrate for AGMO.
Ether lipids inhibit the effects of phorbol diester tumor promoters
Authors: Daniel Larry W. , Etkin Lori A. , Morrison Bennett T. , Parker Judy , Morris‐Natschke Susan , Surles Jefferson R. , Plantadosi Claude
Published: December 2006

Recent studies have shown that the tumor promoter 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA) stimulates protein kinase C (PKC), whereas the ether‐linked phospholipid 1‐O‐octadecyl‐2‐O‐methyl‐rac‐glycerol‐3‐phosphocholine (ET‐18‐OCH3) inhibits PKC activity in vitro. Therefore, the antitumor effects of ET‐18‐OCH3 could be due to its inhibition of PKC activity and the effects of tumor promotion. TPA stimulates arachidonic acid release, prostaglandin synthesis, phosphatidylcholine synthesis and the degradation of phosphatidylcholine by phospholipase C in Madin Darby canine kidney (MDCK) cells. Therefore, we have determined the effects of ET‐18‐OCH3 on these consequences of TPA stimulation. Preliminary experiments determined that ET‐18‐OCH3 inhibited PKC partially purified from MDCK cells by ion‐exchange chromatography on DEAE‐cellulose. In addition, ET‐18‐OCH3, inhibited the TPA‐stimulated phosphorylation of a 40,000‐dalton protein in intact MDCK cells. These data indicate that ET‐18‐OCH3 is an effective inhibitor of PKC activity in MDCK cells. In addition, ET‐18‐OCH3 was found to inhibit arachidonic acid release and prostaglandin synthesis. The inhibition of prostaglandin synthesis appears to be secondary to inhibition of arachidonic acid release, since ET‐18‐OCH3 does not inhibit TPA‐stimulated synthesis of prostaglandin H synthase or the activity of the enzyme directly (Parker, J., Daniel, L. W., and Waite, M. [1987]J. Biol. Chem. 262, 5385–5393). ET‐18‐OCH3 also inhibits TPA‐stimulated phosphatidylcholine synthesis and phosphatidylcholine degradation by phospholipase C. These data provide evidence that the antineoplastic ether lipids inhibit the biochemical effects of the tumor promoter TPA in intact cells and indicate that this inhibition may have a role in their biological activities.
Antitumor activity of synthetic alkylphospholipids with or without PAF activity
Authors: Kudo Ichiro , Nojima Shoshichi , Chang Hyeun Wook , Yanoshita Ryohei , Hayashi Hidetoshi , Kondo Eri , Nomura Hiroaki , Inoue Keizo
Published: December 2006

1‐O‐Octadecyl‐2‐O‐methyl‐sn‐glycero‐3‐phosphocholine (ET‐18‐OMe) has been reported to possess definite antitumor activity in vivo. Twenty‐two alkyl lysophospholipid analogs were chemically synthesized, and their antitumor activity against mouse experimental tumors (Sarcoma 180, MM46, P388) was examined. Among them, 1‐O‐octadecyl‐2‐O‐acetoacetyl‐rac‐glycerol‐3‐phosphocholine was found to show antitumor activity similar to ET‐18‐OMe with less acute toxicity.

Intravenous injection of the ET‐18‐OMe withsn‐3 configuration retarded the subcutaneous growth of Sarcoma 180 cells effectively, while the growth inhibition by thesn‐1 isomer was much less effective. This stereospecificity was similar to that observed in their activities as platelet‐activating factor (PAF) agonists. The acetoacetyl compound, another PAF agonist, showed similar stereospecific antitumor action in vivo. These findings suggest that some alkyl lysophospholipids may activate host cells to a cytostatic stage against tumor cells in vivo through binding to a PAF receptor. Our preliminary results indicated that the responsible cells under these conditions might be primarily immature macrophages present in the bone marrow. No appreciable or even adverse stereospecificity was observed in the different sets of experiments where the activity of ET‐18‐OMe against MM46 tumor cells in vivo or the direct cytotoxicity against human promyelocytic leukemia HL‐60 cells in vitro was examined. Under, some conditions, the antitumor activity of ET‐18‐OMe in vivo may be revealed through direct cytotoxicity and/or modulation of the host defense system by “nonspecific” mechanisms. Some alkylphospholipids without PAF activity may also show antitumor activity through similar, “nonspecific” mechanisms.
Neoplastic cell inhibition with new ether lipid analogs
Authors: Noseda Alessandro , Berens Michael E. , Piantadosi Claude , Modest Edward J.
Published: December 2006

Bioactive phospholipid analogs of platelet‐activating factor (PAF) represent a new approach to cancer chemotherapy. Various modifications of the basic structure of PAF lead to different ether lipid (EL) analogs. Data from the evaluation of thioalkyl and amidoalkyl glycerophosphocholine and of glycerophosphoinositol EL analogs against different experimental tumors in vitro (HL60 and K562 human leukemia cells, BG1 and BG3 ovarian adenocarcinomas) are presented. Exclusion of trypan blue after short exposure to the drugs determined cytotoxicity, and a soft agarose clonogenic assay measured the ability of the analogs to inhibit tumor cell proliferation. The thioalkyl EL are very active against the cell lines using both end points, and the amidoalkyl EL showed efficacy against the leukemic cell lines, whereas the phosphoinositol EL are active only at high concentrations. Combined use of EL analogs, which are membrane‐interactive, with classical DNA‐interactive chemotherapeutic drugs revealed that the combinations have additive antiproliferative effects. These results are promising leads in the development of the anticancer potential of ether lipid analogs.
Cytotoxic effects of ether lipids and derivatives in human nonneoplastic bone marrow cells and leukemic cells in vitro
Authors: Schick Hans D. , Berdel Wolfgang E. , Fromm Michael , Fink Ulrich , Jehn Ulrich , Ulm Kurt , Reichert Anneliese , Eibl Hansjörg , Unger Clemens , Rastetter Johann
Published: December 2006

The effects of 2‐lysophosphatidylcholine (2‐LPC), the alkyl lysophospholipid derivatives (ALP) 1‐O‐octadecyl‐2‐O‐methyl‐rac‐glycero‐3‐phosphocholine (ET‐18‐OCH3) and 1‐O‐hexadecyl‐sn‐glycero‐3‐phospho‐trimethyl‐ammonio‐hexanol, the 2‐acetamide analog of platelet‐activating factor (PAF) 1‐O‐octadecyl‐2‐acetamide‐sn‐glycero‐3‐phosphocholine, the thioether lysophospholipid derivative (TLP) BM 41.440 and the ether‐linked lipoidal amine CP‐46,665 on tritiated thymidine uptake and trypan blue dye exclusion were tested in vitro in various freshly explanted cell samples from human nonneoplastic bone marrow and human leukemias. In both assay systems, a dose range of 1–20 μg/ml of the compounds was tested after 24, 48 and 72 hr of coincubation with the cells.

The trypan blue dye exclusion revealed statistically significant preferential cytotoxicity in leukemic cells for three compounds with the order of quantitative selectiveness: ET‐18‐OCH3>BM41.440>2‐acetamide analog of PAF. CP‐46,665 was the most toxic compound, but did not reveal significant differences between nonneoplastic bone marrow and leukemic cells when added in concentrations greater than 1 μg/ml. The trimethyl‐ammoniohexanol compound showed only minor activity in the majority of tests, when added at concentrations <20 μg/ml. 2‐LPC was rather ineffective.

The tritiated thymidine uptake showed only preferential antiproliferative effects towards leukemic cells of ET‐18‐OCH3 and, sometimes, within the dose time frame tested of BM 41.440. All compounds tested except 2‐LPC and the trimethyl‐ammonio‐hexanol compound were active also in this assay (inhibition of uptake>50% of the controls). Based on these results, ET‐18‐OCH3 and BM 41.440 are recommended for experimental bone marrow purging.
Antineoplastic activity of the thioether lysophospholipid derivative BM 41.440 in vitro
Authors: Fromm Michael , Berdel Wolfgang E. , Schick Hans D. , Fink Ulrich , Pahlke Wulf , Bicker Uwe , Reichert Anneliese , Rastetter Johann
Published: December 2006

Thioether lysophospholipid derivatives (TLP) inhibited the in vitro uptake of [3H]thymidine into blasts of eight leukemias and cells of 12 different solid tumors of human origin. This effect correlated with trypan blue dye exclusion, which was used to assess cell damage.

Cytostatic and cytotoxic effects of TLP were dependent on dosage and incubation time. Destruction of leukemic blasts was completed with >5 μg/ml after an incubation of >48 hr, but 10 to 20 μg/ml were necessary in solid tumors. Ester‐linked 2‐lysophosphatidylcholine was ineffective in the same dose range, which points to the requirement of the alkyl moiety insn‐1 and a stablesn‐2 substitution of the molecule for the antineoplastic effect.

To assess putative antileukemic selectivity, the cytotoxicity (trypan blue dye exclusion) of TLP was compared in human cell samples of 19 non‐neoplastic bone marrows and 9 leukemias. Results revealed a significantly higher activity of the TLP BM 41.440 in leukemic blasts.
Synthesis of thioether phosphocholine analogues
Authors: Bosies Elmar , Herrmann Dieter B. J. , Bicker Uwe , Gall Rudi , Pahlke Wulf
Published: December 2006

The synthesis of thioether phospholipids, which represent a new class of antitumor agents, is reported here. In particular, the route of synthesis of 3‐hexadecylmercapto‐2‐methoxymethylpropyl‐2′‐trimethylammonio‐ethyl phosphate (BM 41.440, Ilmofosine), one of the most potent cytostatic/cytotoxic derivatives, is described in detail. Starting with diethylbis‐hydroxymethylmalonate, ethyl 2‐phenyl‐1,3‐dioxane‐5‐carboxylate is formed via diethyl 2‐phenyl‐1,3‐dioxane‐5,5‐dicarboxylate and 5‐ethoxycarbonyl‐2‐phenyl‐1,3‐dioxane‐5‐carboxylic acid. Reduction of ethyl 2‐phenyl‐1,3‐dioxane‐5‐carboxylate with LiAlH4 affords 5‐hydroxymethyl‐2‐phenyl‐1,3‐dioxane. Alkylation with dimethyl sulfate gives 5‐methoxymethyl‐2‐phenyl‐1,3‐dioxane. The ring structure then is opened byN‐bromosuccinimide, resulting in the formation of 3‐bromo‐2‐methoxymethylpropyl benzoate. Reaction of 3‐bromo‐2‐methoxymethylpropyl benzoate with the sodium salt of hexadecanethiol leads to 3‐hexadecylmercapto‐2‐methoxy‐methylpropanol, which is reacted with a cyclic chlorophosphate to give the corresponding phosphorylated 3‐hexadecylmercapto‐2‐methoxymethylpropanol. Treatment with trimethylamine yields BM 41.440. This compound already has been tested in clinical phase I/II trials in West Germany.
Pharmacokinetics of the thioether phospholipid analogue BM 41.440 in rats
Authors: Herrmann Dieter B. J. , Besenfelder Eberhard , Bicker Uwe , Pahlke Wulf , Böhm Erwin
Published: December 2006

BM 41.440 (1‐hexadecylmercapto‐2‐methoxymethyl‐rac‐glycero‐3‐phosphocholine) is a cytotoxic thioether phospholipid analogue that recently has entered phase I trials in cancer patients. The objective of this study was to evaluate the pharmacokinetics of this compound in female rats after administration of a single oral dose (15 mg/kg body weight [bw]). Furthermore, BM 41.440 serum concentrations were determined under a daily oral treatment of up to 13 weeks. Blood samples were obtained via permanent catheters from the femoral arteries before and after drug administration for a total of 120 hr. Urine was collected in 24 hr‐intervals for 120 hr; the volume was measured, and aliquots were stored at −20 C until analytical determination of the thioether derivative. BM 41.440 was assayed in serum and urine by means of a specific, newly developed reverse‐phase high pressure liquid chromatography technique. Mean maximum serum concentrations (1.7 μg/ml, n=4 animals) were attained after seven hr. A terminal half‐life of ca. 27 hr was calculated from the rate constant for the terminal elimination phase (λz ∼ 0.026/hr). The mean serum BM 41.440 concentration‐time‐area‐under‐the‐curve was 52.9 mg × hr/l. The ratio of total body clearance to absorption fraction was 4.7 ml/min × kg bw. Only a small amount of the drug was found in the urine. The quantity excreted in the urine during a 24 hr‐interval never exceeded 1.5% of the administered dose. Under a daily oral schedule (15 mg/kg bw × day) up to 13 weeks, mean BM 41.440 serum concentrations of 3.3±0.5 μg/ml and 5.2±1.2 μg/ml (mean ±S.D., n=10 animals) were found after five and 13 weeks, respectively. Taken together, the data indicate that BM 41.440 was absorbed from the gastrointestinal tract after oral administration and that accumulation of BM 41.440 can occur in rats.
Wide Resection of Traction Induced Radial Nerve Injury with Cable Grafting Leads to Full Recovery
Authors: Henry Mark
Published: December 2006

The specific clinical setting of high-energy open humerus fractures combined with radial nerve transection has typically led to poor final outcomes with respect to recovery of nerve function. Attention has focused on the issue of an expanded zone of nerve injury induced by longitudinal traction. The fundamental principle of nerve grafting is to bypass the zone of injury. If direct repair or short nerve grafts are placed within the zone of injury, limited recovery should be expected, and this is exactly what has been documented. Wide resection of the zone of traction induced injury, particularly from the distal injured nerve trunk and replacement with long cable grafts has the potential for improved outcomes. Complete nerve recovery to 5/5 manual motor power testing and bilaterally equivalent grip strength is reported in two initial cases treated according to the wide resection plan.
Predictors of adolescent health care utilization
Authors: Vingilis Evelyn , Wade Terrance , Seeley Jane
Published: December 2006

This study, using Andersen's health care utilization model, examined how predisposing characteristics, enabling resources, need, personal health practices, and psychological factors influence health care utilization using a nationally representative, longitudinal sample of Canadian adolescents. Second, this study examined whether this process varies across physicians, non‐physicians, and dentists. The results indicate that need and psychological factors were strong determinants of utilization. Predisposing factors were associated with utilization, although there were few enabling resources. Differences were found for utilization of different services. Females, adolescents who were older, from single parent families, with lower self‐rated health, lower health status, higher disability, higher distress and involved in health compromizing practices were more likely to visit physicians and non‐physicians. Higher dentist utilization was related to higher income, single parent status, being younger, having lower health status, and higher disability. Predisposing and enabling factors were not mediators of utilization. The findings suggest that health care providers could be an important source of counselling on psychological, lifestyle issues, and physical concerns.
Keeping the maintenance of daily life in spite of Chronic Heart Failure. A qualitative study
Authors: Falk Solvig , Wahn Anna-Karin , Lidell Evy
Published: December 2006

Background

Patients with CHF (Chronic Heart Failure) is an increasing group in the society. They often experience increasing powerlessness and depression in daily life as well as difficulties adhering to other physical symptoms. Many patients have difficulties to deal with daily demands.

Aims

To describe how persons, living with CHF, perceived the maintenance of their daily life.

Methods

This study was following a phenomenographic method in order to describe variations of perceptions. Data was collected through taped interviews, taken from 17 patients. The sample was selected from patients attending a specialist Chronic Heart Failure day care unit.

Results

Five main categories were identified from 345 statements describing variations in how patients with CHF kept maintenance in their daily life. The categories include: dealing with the realities of life, dealing with thoughts about life's infinity, taking responsibility, dealing with the surrounding world and keeping up with values of life.

Conclusion

The illness symptoms clearly affected daily routines but participants showed remarkable resolve and showed that values in life could be maintained albeit with a few adjustments. No patient expressed a desire to give up. Understanding patients’ perceptions the specialist nurse can transfer these knowledge to other patients in similar situations.
Structural diversity in the six‐fold redundant set of acyl‐CoA carboxyltransferases in Mycobacterium tuberculosis
Authors: Holton Simon J. , King-Scott Stephanie , Eddine Ali Nasser , Kaufmann Stefan H.E. , Wilmanns Matthias
Published: December 2006

Mycobacterium tuberculosis contains multiple versions of the accA and accD genes that encode the α‐ and β‐subunits of at least three distinct multi‐functional acyl‐CoA carboxylase complexes. Because of its proposed involvement in pathogenic M. tuberculosis survival, the high‐resolution crystal structure of the β‐subunit gene accD5 product has been determined and reveals a hexameric 356 kDa complex. Analysis of the active site properties of AccD5 and homology models of the other five M. tuberculosis AccD homologues reveals unexpected differences in their surface composition, providing a molecular rational key for a sorting mechanism governing correct acyl‐CoA carboxylase holo complex assembly in M. tuberculosis.
Solution structure and NMR characterization of the binding to methylated histone tails of the plant homeodomain finger of the tumour suppressor ING4
Authors: Palacios Alicia , Garcia Pascal , Padró Daniel , López-Hernández Eva , Martín Irene , Blanco Francisco J.
Published: December 2006

Plant homeodomain (PHD) fingers are frequently present in proteins involved in chromatin remodelling, and some of them bind to histones. The family of proteins inhibitors of growth (ING) contains a PHD finger that bind to histone‐3 trimethylated at lysine 4, and those of ING1 and ING2 also act as nuclear phosphoinositide receptors. We have determined the structure of ING4 PHD, and characterised its binding to phosphoinositides and histone methylated tails. In contrast to ING2, ING4 is not a phosphoinositide receptor and binds with similar affinity to the different methylation states of histone‐3 at lysine 4.