bluuebunny/crossref_metadata_2025 huggingface dataset:
Lateral Lithiation Reactions Promoted by Heteroatomic Substituents
Authors: Clark Robin D. , Jahangir Alam
Published: November 2004

Heteroatom‐facilitated lithiation reactions have assumed an increasingly important role in the elaboration of carbocyclic aromatic and heteroaromatic systems in the 40 years subsequent to the seminal review on metalation with organolithium reagents by Gilman and Morton. Of particular note has been the development of methodology for the lateral lithiation of alkyl‐substituted aromatic systems promoted by an extensive array of heteroatomic substituents. These lithiations involve deprotonation at a benzylic (side chain) position that is lateral to, or flanked by, a heteroatom‐containing substituent (G); this substituent facilitates lithiation relative to the parent system in which G is not present. The derived lithiated species have great synthetic utility for functionalization of benzylic sites, for chain extensions, and for the synthesis of fused carbocyclic and heterocyclic systems via annelation processes. This chapter summarizes the significant amount of work reported on heteroatom‐facilitated lateral lithiations and the synthetic applications thereof. The survey covers the substituents that promote these reactions, and the methods of formation, stability, reactivity, and synthetic utility of the lithiated species.

Coverage is limited to examples in which the R
1
group in the representative equation is hydrogen (toluene derivatives), alkyl, or aryl. Examples that would be better classified as
alpha
‐lithiations are not covered, for example, where R
1
is an anion‐stabilizing group such as cyano, carboxy, and so on. Rare examples of lithiations of alkyl groups that are
meta
or
para
to the facilitating group G are included in the chapter, although these are not, strictly speaking, lateral lithiations. Also included are a limited number of older lateral metalations that were originally effected with sodium or potassium bases but would now be more conveniently carried out with lithium dialkylamide bases.

The aromatic nucleus may be carbocyclic or heterocyclic, but lateral lithiations of heterocycles lacking the heteroatomic substituent are not covered. For example, lithiation of nicotinamides (Eq. 2) are included; however, lithiations of picolines, and other heterocyclic systems, are considered beyond the scope of this chapter.

The relationship of lateral lithiation reactions to heteroatom‐facilitated
ortho
lithiations is obvious and the two fields have developed, for the most part, in concert. With several notable exceptions, the same heteroatomic substituents (G) promote both types of lithiations. A number of reviews cover various aspects of
ortho
lithiation reactions, including the comprehensive chapter in
Organic Reactions
by Gschwend and Rodriguez that surveyed the literature to 1979. In the present chapter, the relationship of lateral lithiation and
ortho
lithiation reactions is discussed within the contexts of mechanism, reactivity, and synthetic utility. In addition, the sequential use of these two lithiation processes for the synthesis of complex aromatic and heteroaromatic systems is covered.
Glycosylation with Sulfoxides and Sulfinates as Donors or Promoters
Authors: Crich David , Lim Linda B. L.
Published: November 2004

The efficient, stereocontrolled formation of glycosidic bonds is arguably the most fundamental reaction in glycoscience. This chapter surveys four recent distinct glycosylation methods united by the common theme of employing sulfoxides, or closely related sulfinates, either in the glycosyl donor itself or as an integral part of the promoter. In the first method (the sulfoxide method), a glycosyl sulfoxide, the donor, is coupled to an acceptor alcohol by means of an activating agent to give the glycosidic bond. The activating agent is typically triflic anhydride, but other compounds have been used.

In the second method (the thiogylcoside method) the donor is thioglycoside. It is activated by means of a promoter derived from the reaction of trifluoromethanesulfonic anhydride and thiosulfinate, a sulfinaminde, or diphenylsulfoxide before coupling to an acceptor alcohol. The third method is dehydrative coupling. This chapter is concerned only with the recent variations in which dehydration is achieved by means of a combination of diaryl sulfoxides and trifluoromethanesulfonic acid. The last method (the oxidative method), involves the direct oxidative glycosylation of glycals. This method differs significantly from the other methods since it does not employ a traditional anomeric derivative as glycosly donor, but derives one from the formal oxidation of glycal.

At some time in the activation process, all four methods typically involve the reaction of a sulfoxide, or sulfinate with trifluoromethanesulfonic anhydride. All four methods possess the distinct advantage of using readily prepared, stable gylcosyl donors. Three of them are metal‐free and two of them are capable of coupling to enable the most hindered unreactive alcohols in a matter of minutes at low temperature. These methods are some of the most powerful available for the formation of glycosidic linkages.
Silica Particles: A Novel Drug‐Delivery System
Authors: Barbé C. , Bartlett J. , Kong L. , Finnie K. , Lin H. Q. , Larkin M. , Calleja S. , Bush A. , Calleja G.
Published: November 2004

In recent decades, significant advances in drug‐delivery systems have enabled more effective drug administration. To deliver drugs to specific organs, a range of organic systems (e.g., micelles, liposomes, and polymeric nanoparticles) have been designed. They suffer from limitations, including poor thermal and chemical stability, and rapid elimination by the immune system. In contrast, silica particles offer a biocompatible, stable, and “stealthy” alternative. Bioactive molecules can be easily encapsulated within silica particles by combining sol–gel polymerization with either spray‐drying or emulsion chemistry. Spray‐drying faces challenges, including low yield, surface segregation, and size limitations. In contrast, sol–gel emulsions enable the production of nanoparticles with homogeneous drug distribution, and permit ambient temperature processing, necessary for handling biologicals. Independent control of the size and release rate can be readily achieved. Preliminary in‐vivo experiments reveal enhanced blood stability of the nanoparticles, which, coupled with sustained release of anti‐tumor agents, show good potential for cancer treatment.
Materials Science at the Small Scale
Authors: Levy E.
Published: November 2004

Science at the nanometer scale is currently receiving great attention from the materials science community and represents a significant proportion of the manuscripts both received and published by Advanced Materials. The Editor of Advanced Materials discusses the impact of this development, and explains how the new journal from Wiley‐VCH, Small, will help to meet the challenge of serving this community's needs.
Comparison of Pulsed Electrochemical Detection Modes Coupled with Microchip Capillary Electrophoresis
Authors: García Carlos D. , Henry Charles S.
Published: November 2004

There is a need to develop analytical methods that are capable of rapidly measuring small biological markers in the field of metabolomics. Among others, carbohydrates play an important role biologically yet are traditionally hard to detect since they have no chromophore or fluorophore. In the present report, the first application of integrated pulsed amperometric detection (iPAD) coupled with microchip electrophoresis to the analysis of glucose, mannose, sucrose, maltose, glucosamine, lactose, maltotriose and galactose is demonstrated. iPAD is an electrochemical detection mode that can be used for direct detection of carbohydrates, amines and sulfur containing compounds. The effect of different solution parameters, including the buffer concentration, pH and the concentration of SDS on both separation and detection response was analyzed. In addition, a comparison study between PAD and iPAD was performed using glucose, glucosamine, sucrose and maltose as model carbohydrates.
Resistance to Surfactant and Protein Fouling Effects at Conducting Diamond Electrodes
Authors: Shin Dongchan , Tryk Donald A. , Fujishima Akira , Merkoçi Arben , Wang Joseph
Published: November 2004

Boron‐doped diamond thin‐film electrodes display negligible fouling effects in the presence of high levels of surface‐active materials, including proteins. Dramatic improvements in the stability of the analyte response (compared to common glassy carbon and carbon paste electrodes) are illustrated using bovine serum albumin (BSA), gelatin, and Triton X‐100 in connection with repetitive square‐wave voltammetric (SWV) measurements. The voltammetric response of ascorbic acid at the diamond electrode exhibits negligible shifts in peak potentials and minimal depressions of current signals over a wide range of surfactant concentrations (0–750 ppm). For example, the diamond electrode exhibited 70, 50 and 60 mV potential shifts for 10 repetitive voltammetric scans in the presence of 100 ppm BSA, gelatin and Triton X‐100, respectively, compared to 120, 190, and 280 mV shifts observed at the glassy carbon electrode. Furthermore, only 4.3 and 6.2% of the initial current decays were observed in the presence of 100 ppm Triton X‐100 and gelatin, respectively (compared to 45.2 and 34.4% diminutions at the glassy carbon electrode). Such improved performance was also confirmed from the SWV measurements of uric acid, dihydroxyphenylacetic acid, and catechol. The greatly improved resistance to surfactant interference reflects the fact that the as‐grown diamond thin film, composed of oxide‐free and hydrogen‐terminated surface, has a relatively lower surface energy and minimal electrostatic attributes, either specific or general, so that little adsorption of surface‐active agents occurs. The topographic AFM images of the diamond electrode surface confirm a negligible BSA fouling effect after repetitive SWV measurements. Such enhanced antifouling features make diamond electrodes very attractive for numerous real‐life electroanalytical applications.
Aroma compounds in Oregon Pinot Noir wine determined by aroma extract dilution analysis (AEDA)
Authors: Fang Yu , Qian Michael
Published: November 2004

The aroma proﬁles of Oregon Pinot Noir wines were investigated with aroma extract dilution analysis (AEDA). The wines were extracted with pentane‐diethyl ether, the aromas were distilled using solvent‐assisted ﬂavour evaporation (SAFE) and separated into acidic/water‐soluble and neutral/basic fractions. In the acidic/water‐soluble fraction, 2‐phenylethanol and 3‐methyl‐1‐butanol showed the highest AEDA values, followed by 2‐methylpropanoic acid, butanoic acid, 2‐methylbutanoic acid, 3‐methylbutanoic acid, 2‐methylpropanol, hexanol, trans‐3‐hexenol, cis‐3‐hexenol, benzyl alcohol, 3‐methylthio‐1‐propanol, 3‐ethylthio‐1‐propanol, linalool and geraniol (all with FD ≥ 64). In the neutral/basic fraction, ethyl 2‐methylpropanoate, ethyl butanoate, 3‐methylbutyl acetate, ethyl hexanoate, and benzaldehyde had very high AEDA values (all with FD ≥ 64), followed by ethyl 3‐methylbutanoate, 3‐methylbutyl 2‐methylpropanoate, ethyl octanoate, ethyl decanoate, benzyl acetate, phenylethyl formate, phenylethyl acetate, ethyl dihydrocinnamate, ethyl anthranilate, 3‐methylthio‐1‐propanal, citronellal, whisky lactone and γ‐nonalactone (all with FD ≥ 16). Overall, the results indicated that there is no single compound that characterizes the aroma of Pinot Noir, and that the characteristic aroma comes from a blend of numerous compounds. Copyright © 2004 John Wiley & Sons, Ltd.
Bradykinin‐induced p42/p44 MAPK phosphorylation and cell proliferation via Src, EGF receptors, and PI3‐K/Akt in vascular smooth muscle cells
Authors: Yang Chuen‐Mao , Lin Meng‐I , Hsieh Hsi‐Lung , Sun Chi‐Chin , Ma Yunn‐Hwa , Hsiao Li‐Der
Published: November 2004

In our previous study, bradykinin (BK) exerts its mitogenic effect through Ras/Raf/MEK/MAPK pathway in vascular smooth muscle cells (VSMCs). In addition to this pathway, the non‐receptor tyrosine kinases (Src), EGF receptor (EGFR), and phosphatidylinositol 3‐kinase (PI3‐K) have been implicated in linking a variety of G‐protein coupled receptors to MAPK cascades. Here, we investigated whether these different mechanisms participating in BK‐induced activation of p42/p44 MAPK and cell proliferation in VSMCs. We initially observed that BK‐ and EGF‐dependent activation of Src, EGFR, Akt, and p42/p44 MAPK and [3H]thymidine incorporation were mediated by Src and EGFR, because the Src inhibitor PP1 and EGFR kinase inhibitor AG1478 abrogated BK‐ and EGF‐dependent effects. Inhibition of PI3‐K by LY294002 attenuated BK‐induced Akt and p42/p44 MAPK phosphorylation and [3H]thymidine incorporation, but had no effect on EGFR phosphorylation, suggesting that EGFR may be an upstream component of PI3‐K/Akt and MAPK in these responses. This hypothesis was supported by the tranfection with dominant negative plasmids of p85 and Akt which significantly attenuated BK‐induced Akt and p42/p44 MAPK phosphorylation. Pretreatment with U0126 (a MEK1/2 inhibitor) attenuated the p42/p44 MAPK phosphorylation and [3H]thymidine incorporation stimulated by BK, but had no effect on Akt activation. Moreover, BK‐induced transactivation of EGFR and cell proliferation was blocked by matrix metalloproteinase inhibitor GM6001. These results suggest that, in VSMCs, the mechanism of BK‐stimulated activation of p42/p44 MAPK and cell proliferation was mediated, at least in part, through activation of Src family kinases, EGFR transactivation, and PI3‐K/Akt. Copyright © 2004 Wiley‐Liss, Inc.
HIV‐1 Tat protein concomitantly down‐regulates apical caspase‐10 and up‐regulates c‐FLIP in lymphoid T cells: A potential molecular mechanism to escape TRAIL cytotoxicity
Authors: Gibellini Davide , Carla Re Maria , Ponti Cristina , Vitone Francesca , Bon Isabella , Fabbri Greta , Grazia Di Iasio Maria , Zauli Giorgio
Published: November 2004

In this study, we showed the existence of a positive correlation between the amount of human immunodeficiency virus‐type 1 (HIV‐1) RNA in HIV‐1 seropositive subjects and the plasma levels of TRAIL. Since it has been previously demonstrated that HIV‐1 Tat protein up‐regulates the expression of TRAIL in monocytic cells whereas tat‐expressing lymphoid cells are more resistant to TRAIL cytotoxicity, we next investigated the effect of Tat on the expression/activity of both apical caspase‐8 and ‐10, which play a key role in mediating the initial phases of apoptosis by TRAIL, and c‐FLIP. Jurkat lymphoblastoid human T cell lines stably transfected with a plasmid expressing wild‐type (HIV‐1) tat gene showed normal levels of caspase‐8 but significantly decreased levels of caspase‐10 at both mRNA and protein levels with respect to Jurkat transfected with the control plasmid or with a mutated (cys22) non‐functional tat cDNA. A significant decrease of caspase‐10 expression/activity was also observed in transient transfection experiments with plasmid carrying tat cDNA. Moreover, c‐FLIPL and c‐FLIPS isoforms were up‐regulated in tat‐expressing cells at both mRNA and protein level in comparison with control cells. Taken together, these results provide a molecular basis to explain the resistance of tat‐expressing Jurkat cells to apoptosis induced by TRAIL and, possibly, to other death‐inducing ligands. © 2004 Wiley‐Liss, Inc.
Urokinase plasminogen activator receptor promotes macrophage infiltration into the vascular wall of ApoE deficient mice
Authors: Gu Jian‐Ming , Johns Anthony , Morser John , Dole William P. , Greaves David R. , Deng Gary G.
Published: November 2004

The urokinase plasminogen activator receptor (uPAR) regulates macrophage adhesion and migration by binding directly to matrix proteins and signaling through integrin complexes. In this study, we examined the role of uPAR on macrophage infiltration into the vascular wall. Stable murine macrophage (Raw264.7) cell lines expressing high levels of human uPAR, human urokinase plasminogen activator (uPA), or both were established using expression vectors driven by the human CD68 promoter. Stimulation with human uPA specifically induced phosphorylation of early response regulated kinase (ERK) in cells expressing human uPAR but not in sham transfected cells. The human uPAR expressing Raw264.7 cells showed increased adhesion to both human uPA and vitronectin (Vn). Raw264.7 cells expressing human uPAR or both human uPAR and uPA, but not uPA alone, were detected in the aortic wall of ApoE−/− mice, and no cells were detected in that of age‐matched C57BL/6J mice after intravenous infusion of the cells. Blocking of Mac‐1/ICAM‐1 interaction by anti‐αM antibody (M1/70) significantly reduced the infiltration of huPAR‐expressing Raw264.1 cells into aorta of ApoE−/− mice. Treatment of C57BL/6J mice with angiotensin II resulted in infiltration of Raw264.7 cells expressing human uPAR. These data demonstrate that uPAR plays a key role in promoting macrophage infiltration into the arterial wall of ApoE−/− mice. © 2004 Wiley‐Liss, Inc.
The synthesis of a benzamidine‐containing NR2B‐selective NMDA receptor ligand labelled with tritium or fluorine‐18
Authors: Hamill Terence G. , McCauley John A. , Burns H. Donald
Published: November 2004

A novel tritium or flourine‐18‐labelled benzamidine‐containing NR2B‐selective NMDA receptor ligand has been synthesized. This compound was designed to contain the fluoromethoxy group to allow for the synthesis of a high specific activity, fluorine‐18‐labelled PET tracer for imaging studies of the NR2B receptor. In addition to the fluorine‐18‐labelled compound, this compound was also tritium labelled. The tritiated ligand (11 Ci/mmol) was synthesized by a gas tritiation reaction of an aryl bromide precursor. The fluorine‐18 ligand (2916 Ci/mmol), which was deuterated in the fluoromethoxy group to aid in metabolic stability, was synthesized by alkylating a phenolic precursor with [18F]fluoromethylbromide‐d2. Copyright © 2004 John Wiley & Sons, Ltd.
N‐Arylation of indoles with 4‐[18F]fluoroiodobenzene: synthesis of 18F‐labelled σ2 receptor ligands for positron emission tomography (PET)
Authors: Wüst Frank R. , Kniess Torsten
Published: November 2004

The palladium‐mediated N‐arylation of indoles with 4‐[18F]fluoroiodobenzene as a novel radiolabelling method has been developed. Optimized reaction conditions were elaborated by variation of different catalyst systems (CuI/1,2‐diamines and Pd2(dba)3/phosphine ligands), bases and solvents in the reaction of indole with 4‐[18F]fluoroiodobenzene. Optimized reaction conditions (Pd2(dba)3/(2‐(dicyclohexyl‐phosphino)‐2′‐(N,N‐dimethylamino)‐biphenyl, NaOBut, toluene, 100°C for 20 min) were applied for the synthesis of 18F‐labelled σ2 receptor ligands [18F]‐11 and [18F]‐13 which were obtained in 91 and 84% radiochemical yields, respectively. Copyright © 2004 John Wiley & Sons, Ltd.
Synthesis and biological characterization of 99mTc(I) tricarbonyl cysteine complex, a potential diagnostic for assessment of renal function
Authors: Park Sang Hyun , Jang Beom Su , Park Kyung Bae
Published: November 2004

Cysteine containing three functional groups, i.e. a carboxyl, sulfhydryl, and amino group, has been labelled with 99mTc(I) tricarbonyl precursor (2) in order to study the renal characteristics of the resulting 99mTc(I) tricarbonyl cysteine (3) versus the reference 99mTc‐MAG3 (1). The 99mTc(I) tricarbonyl cysteine (3) was prepared in good yields and characterized by HPLC, eletrophoresis, and eletrospray mass spectrometry. The plasma protein binding rate of 99mTc(I) tricarbonyl cysteine (3) was about 70 to 80%, and similar to that of 131I‐OIH (70%) but lower than that of 99mTc‐MAG3 (90%). The T1/2 of 99mTc(I) tricarbonyl cysteine (4.30±0.79 min) in the kidney was higher than the one of 99mTc‐MAG3 (2.43±0.70 min). The static image of 99mTc(I) tricarbonyl cysteine at 5 min post injection showed high concentrated activity in the kidney. And in the 15, 30 min post injection images, most activity appeared in the bladder without a residue in other organs. The 99mTc(I) tricarbonyl cysteine exhibited biological behavior comparable to 99mTc‐MAG3 and it is expected to have diagnostic potential for imaging renal function in nuclear medicine. Copyright © 2004 John Wiley & Sons, Ltd.
Differential response of glutamine in cultured neurons and astrocytes
Authors: Rama Rao K.V. , Jayakumar A.R. , Norenberg M.D.
Published: November 2004

Glutamine, a byproduct of ammonia detoxification, is found elevated in brain in hepatic encephalopathy (HE) and other hyperammonemic disorders. Such elevation has been implicated in some of the deleterious effects of ammonia on the central nervous system (CNS). Recent studies have shown that glutamine results in the induction of the mitochondrial permeability transition (MPT) in cultured astrocytes. We examined whether glutamine shows similar effects in cultured neurons. Both cultured astrocytes and neurons were exposed to glutamine (6.5 mM) for 24 hr and the MPT was assessed by changes in cyclosporin A (CsA)‐sensitive inner mitochondrial membrane potential (ΔΨm) using the potentiometric dye tetramethylrhodamine ethyl ester (TMRE). Glutamine significantly dissipated the ΔΨm in astrocytes as demonstrated by a decrease in mitochondrial TMRE fluorescence, a process that was blocked by CsA. On the other hand, treatment of cultured neurons with glutamine had no effect on the ΔΨm. Dissipation of the ΔΨm in astrocytes by glutamine was blocked by treatment with 6‐diazo‐5‐oxo‐L‐norleucine (DON; 100 μM), suggesting that glutamine hydrolysis and the subsequent generation of ammonia, which has been shown previously to induce the MPT, might be involved in MPT induction by glutamine. These data indicate that astrocytes but not neurons are vulnerable to the toxic effects of glutamine. The selective induction of oxidative stress and the MPT by glutamine in astrocytes may partially explain the deleterious affects of glutamine on the CNS in the setting of hyperammonemia, as well as account for the predominant involvement of astrocytes in the pathogenesis of HE and other hyperammonemic conditions. © 2004 Wiley‐Liss, Inc.
Cellular and subcellular distribution of monocarboxylate transporters in cultured brain cells and in the adult brain
Authors: Pellerin Luc , Halestrap Andrew P. , Pierre Karin
Published: November 2004

Monocarboxylate transporters (MCTs) are involved in the uptake and release of lactate, pyruvate, and ketone bodies. Studies of their distribution at both the mRNA and protein levels have highlighted the specific expression of MCT1, MCT2, and more recently MCT4 in the central nervous system. MCT1 was found strongly expressed by cortical astrocytes both in vitro and in vivo. It was also found at high levels on blood vessels, ependymocytes, and glia limitans. A subset of neurons in vitro exhibited a weak but significant MCT1 expression. In contrast, it was determined that MCT2 represents the predominant neuronal MCT on cultured neurons as well as on neurons throughout the brain parenchyma. At the subcellular level, part of MCT2 is located in postsynaptic densities. Specific populations of astrocytes in the white matter also exhibited MCT2 expression in the rat, but not in the mouse brain. MCT4 was found exclusively in astrocytes in several areas including the cortex, the hippocampus, and the cerebellum. MCT2 expression increased in cultured neurons with days in vitro commensurate with increased synapse formation. Moreover, a significant increase in MCT2 expression was observed in cultured neurons exposed to noradrenaline, an effect involving a regulation at the translational level. The description of MCTs on different cell types in the central nervous system together with clear evidence for regulation of their expression further emphasize the important role that monocarboxylates, and particularly lactate, might play in brain energy metabolism not only during development but also in the adult. © 2004 Wiley‐Liss, Inc.
Lactate utilization by brain cells and its role in CNS development
Authors: Medina José M. , Tabernero Arantxa
Published: November 2004

We studied the role played by lactate as an important substrate for the brain during the perinatal period. Under these circumstances, lactate is the main substrate for brain development and is used as a source of energy and carbon skeletons. In fact, lactate is used actively by brain cells in culture. Neurons, astrocytes, and oligodendrocytes use lactate as a preferential substrate for both energy purposes and as precursor of lipids. Astrocytes use lactate and other metabolic substrates for the synthesis of oleic acid, a new neurotrophic factor. Oligodendrocytes mainly use lactate as precursor of lipids, presumably those used to synthesize myelin. Neurons use lactate as a source of energy and as precursor of lipids. During the perinatal period, neurons may use blood lactate directly to meet the need for the energy and carbon skeletons required for proliferation and differentiation. During adult life, however, the lactate used by neurons may come from astrocytes, in which lactate is the final product of glycogen breakdown. It may be concluded that lactate plays an important role in brain development. © 2004 Wiley‐Liss, Inc.
Rasagiline: Neurodegeneration, neuroprotection, and mitochondrial permeability transition
Authors: Youdim Moussa B.H. , Bar Am Orit , Yogev‐Falach Merav , Weinreb Orly , Maruyama Wakako , Naoi Makato , Amit Tamar
Published: November 2004

Mitochondria are involved directly in cell survival and death. The assumption has been made that drugs that protect mitochondrial viability and prevent apoptotic cascade‐induced mitochondrial permeability transition pore (MPTp) opening will be cytoprotective. Rasagiline (N‐propargyl‐1R‐aminoindan) is a novel, highly potent irreversible monoamine oxidase (MAO) B inhibitor anti‐Parkinson drug. Unlike selegiline, it is not derived from amphetamine, and is not metabolized to neurotoxic L‐methamphetamine derivative. In addition, it does not have sympathomimetic activity. Rasagiline is effective as monotherapy or adjunct to levodopa for patients with early and late Parkinson's disease (PD) and adverse events do not occur with greater frequency in subjects receiving rasagiline than in those on placebo. Phase III controlled studies indicate that it might have a disease‐modifying effect in PD that may be related to its neuroprotective activity. Its S isomer, TVP1022, is more than 1,000 times less potent as an MAO inhibitor. Both drugs, however, have neuroprotective activity in neuronal cell cultures in response to various neurotoxins, and in vivo in response to global ischemia, neurotrauma, head injury, anoxia, etc., indicating that MAO inhibition is not a prerequisite for neuroprotection. Their neuroprotective effect has been demonstrated to be associated directly with the propargylamine moiety, which protects mitochondrial viability and MTPp by activating Bcl‐2 and protein kinase C (PKC) and by downregulating the proapoptotic FAS and Bax protein families. Rasagiline and its derivatives also process amyloid precursor protein (APP) to the neuroprotective, neurotrophic, soluble APP α (sAPPα) by PKC‐ and MAP kinase‐dependent activation of α‐secretase. The identification of the propargylamine moiety as the neuroprotective component of rasagiline has led us to development of novel bifunctional anti‐Alzheimer drugs (ladostigil) possessing cholinesterase and brain‐selective MAO inhibitory activity and a similar neuroprotective mechanism of action. © 2004 Wiley‐Liss, Inc.
Impacts and risks associated with developing, but unsupervised, stingray tourism at Hamelin Bay, Western Australia
Authors: Newsome David , Lewis Anna , Moncrieff Daryl
Published: November 2004

Interacting with stingrays at Hamelin Bay, in the south‐west of Western Australia, appears to be substantially growing in popularity. Promotion of the rays is increasing through websites and brochures and larger tourism productions, such as the ‘Getaway’ television programme, have shown interest in the Hamelin Bay site. Yet there is still very little known about the impacts on rays (both behavioural and physical), risks to humans, or indeed the issues that provisioning stingrays can present. Although Shackley (1998) conducted an impact study of stingray provisioning in the Cayman Islands, provisioning activities at Hamelin Bay, and other areas in the southwest are unique because they are shore‐based. As part of developing a profile of conditions at the Hamelin Bay provisioning site we investigated stingray numbers and their distribution in the area. We also collected data on the type and amount of provisioned food, investigated stingray behaviour and observed how tourists interacted with stingrays. It was shown through site profile data that rays are attracted to the site principally by food provisioning and secondarily by boats due to learned association with food. They are most common at the provisioning site in the middle of the day, as are peak visitor numbers.

Behavioural impacts on rays were found to be attraction to humans, resulting in aggression and hierarchy towards one another. Attraction to humans at the provisioning site reflected that the rays may be partially habituated. However, rays were also seen foraging naturally for food, indicating that they are not yet dependent on humans. Other potential impacts to rays include boat damage from pleasure craft, overfeeding, being fed the wrong food, damage from fishing hooks and risk of disease from foul water. Lesions on skin and permanent shoaling behaviour, as witnessed at other stingray provisioning sites, were not observed at Hamelin Bay. Management actions are recommended to reduce impacts on the rays, eliminate risks to visitors and increase visitor satisfaction. Copyright © 2004 John Wiley & Sons, Ltd.
‘When buying into the business, we knew it was seasonal’: perceptions of seasonality in Central Otago, New Zealand
Authors: Duval David Timothy
Published: November 2004

Although the majority of the academic literature makes a convincing economic case when suggesting that seasonality is problematic, it is, arguably, equally important to consider whether businesses themselves perceive seasonality as a distinct problem. This paper considers the extent to which businesses and operations, variably involved in tourism, perceive seasonality. A case study of the Central Otago region of New Zealand is offered. The results suggest that although seasonality is perceived as a salient issue for the sector itself, it is not universally perceived to be inherently problematic from the perspective of the individual business/operator. Copyright © 2004 John Wiley & Sons, Ltd.
A classification framework and management approach for the sustainable use of natural assets used for tourism
Authors: Hughey Kenneth F.D. , Ward Jonet C. , Crawford Kirsten A. , McConnell Lesley , Phillips Jeremy G. , Washbourne Robyn
Published: November 2004

There is growing concern internationally about how best to sustainably manage natural assets used by tourists. Existing approaches lack a coherent framework around which like‐assets can be clustered and managed consistently. In this paper we propose an integrated framework which provides for a simple‐to‐use asset classification system, management guidelines based on the relationship between importance and fragility of the asset, and a set of indicators based on the pressure–state–response model for monitoring management progress. Copyright © 2004 John Wiley & Sons, Ltd.
New Vistas in Frontal Polymerization
Authors: Mariani Alberto , Bidali Simone , Fiori Stefano , Malucelli Giulio , Ricco Laura
Published: November 2004

Frontal Polymerization is a technique for the synthesis of polymers that, by exploiting the heat liberated by the self‐same reaction, generates a hot front that can sustain and propagate itself from one end of the reactor to the other converting monomer into polymer. After the activation and following formation of the front, it is not necessary to provide any other form of energy in order to carry out polymerization. In this article we will summarize some of the recent results we have obtained in the application of Frontal Polymerization to the preparation of polyurethanes, unsaturated polyester resins, and polyacrylates.
Process Design of Fluorinated Polyurethane‐Urea Anionomer Aqueous Dispersions
Authors: Turri Stefano , Levi Marinella , Trombetta Tania
Published: November 2004

A series of anionomeric polyurethane‐ureas containing perfluoropolyether (PFPE) segments was obtained with a process consisting of a prepolymerisation step, followed by dispersion in water and chain extension. The anionomeric prepolymer can be dispersed in water according to the “prepolymer mixing method” (prepolymer added to water under stirring, or viceversa), then the diamine chain extender is added to form urea linkages. Some compositive parameters (amount of COOH groups in the polymer, diamine content) were optimised in order to obtain fine (diameter 60‐90 nm), stable and narrow distribution polymer particles even with a limited amount of ionomer content (COOH = 0.20‐0.25 eq/Kg). The fluid dynamics and process engineering of the dispersion step were finally discussed, defining optimal mixing conditions for obtaining controlled and highly reproducible results.
Synthesis and Characterization of Star‐Branched Nylon 12
Authors: Farina Hermes , Yuan Cui Ming , Ortenzi Marco , Di Silvestro Giuseppe
Published: November 2004

Linear and star‐branched polyamide 12 were prepared in the presence of mono‐ and multifunctional acid agents. Molecular masses and molecular mass distributions are discussed according to our model recently presented and are compared with the data obtained by Flory's model. End group titration and SEC data are discussed. Oligomerisation data confirm the general validity of our model.
The Effects of Cold Plasma Treatments on LDPE Wettability and Curing Kinetic of a Polyurethane Adhesive
Authors: Bronco Simona , Bertoldo Monica , Taburoni Elisa , Cepek Cinzia , Sancrotti Massimo
Published: November 2004

A cold plasma feed with either oxygen or nitrogen was used to modify thin Low Density Polyethylene films. The treatment improved both the surface wettability and the curing kinetic of a polyurethane based adhesive spread on the surface. The chemical functionalities responsible of the observed behaviours were investigated and monitored over time by high resolution x‐ray photoelectron spectroscopy. Atomic force microscopy were used to compare the effects of the two feeding gases on the surface morphology of films exposed (to the plasma) for equal times. The effect on the treated films of the atmosphere exposure and of the aging time were also considered.
Thermo‐Mechanical and Morphological Characterization of Plasticized Poly[(R)‐3‐hydroxybutyric acid]
Authors: Grillo Fernandes E. , Pietrini M. , Chiellini E.
Published: November 2004

Blends of poly[(R)3‐hydroxybutyryric acid) (PHB) with different plasticizers were investigated by TGA, DSC, OM and mechanical testing. Markedly hydrophilic plasticizers promote PHB thermal‐degradation through a light alcoholysis reaction. All the used plasticizers were compatible with PHB up to a maximum load of 5 wt‐%. Higher loads were recorded with increasing of plasticizer molecular weight.
Methacrylic Polymers Bearing in the Side‐Chain an Optically Active Moiety Linked to the trans‐4‐Azobenzene Chromophore: Chiroptical Properties of Poly[(S)‐(+)‐N‐methyl‐(2‐methacryloyloxypropanoyl)‐4‐aminoazobenzene]
Authors: Angiolini Luigi , Giorgini Loris , Salatelli Elisabetta
Published: November 2004

The synthesis by radical homopolymerization of a novel optically active methacrylic polymer containing a side‐chain chiral moiety linked to a photochromic chromophore has been carried out starting from the related monomer trans‐(S)‐(+)‐N‐methyl‐(2‐methacryloyloxypropanoyl)‐4‐aminoazobenzene. The chiroptical properties in solution of the polymer have been investigated by circular dichroism and compared with those of the corresponding low molecular weight model compound, trans‐(S)‐(+)‐N‐methyl‐(2‐pivaloyloxypropanoyl)‐4‐aminoazobenzene. The optical activity displayed by the polymer is discussed in terms of extent of chiral conformations assumed by the macromolecules as a consequence of dipole‐dipole interactions between the azoaromatic chromophores.
Chitosan and Poly(vinyl pyrrolidone): Compatibility and Miscibility of Blends
Authors: Marsano Enrico , Vicini Silvia , Skopiǹska Joanna , Wisniewski Marcin , Sionkowska Alina
Published: November 2004

The miscibility of chitosan and poly(vinyl pyrrolidone) −PVP‐ has been studied by viscosity measurements, differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). For chitosan/PVP blends in solid state (thin films) interaction were found by FTIR and DSC methods. After blending PVP with chitosan the glass transition temperature Tg was altered, this may be a result of hydrogen bonds between the synthetic and biological component. It was found that solution of chitosan and PVP are immiscible, viscosimetry methods showed that interactions between chitosan and PVP are to small for the predictions of miscibility, due to the high affinity of the two polymers for the solvent. The study of blends with bespoke structural and properties will be essential for the development of a new generation of biocompatible stimuli‐sensitive hydrogels.
Effect of SBS on Rheological Properties of Different Base Asphalts
Authors: Polacco Giovanni , Biondi Dario , Stastna Jiri , Vlachovicova Zora , Zanzotto Ludovit
Published: November 2004

In this note rheological properties of two different polymer modified asphalts (PMA) are compared. PMAs were prepared from two different base asphalts, a soft one (200/300 Pen grade) and a hard one (70/100 Pen grade), by addition of 4% by weight of radial SBS as modifier. Dynamic mechanical properties were determined in a wide temperature range for bases and modified asphalts both before and after artificial aging. As expected, the moduli of the soft base are more sensitive to polymer addition and the two PMAs attain similar maximum values after aging. However a significant difference in the frequency at which the maxima of the loss modulus are reached is maintained within the two materials irrespectively of aging or polymer addition.
Global existence of the radially symmetric solutions of the Navier–Stokes equations for the isentropic compressible fluids
Authors: Choe Hi Jun , Kim Hyunseok
Published: November 2004

We study the isentropic compressible Navier–Stokes equations with radially symmetric data in an annular domain. We first prove the global existence and regularity results on the radially symmetric weak solutions with non‐negative bounded densities. Then we prove the global existence of radially symmetric strong solutions when the initial data ρ0, u0 satisfy the compatibility condition

for some radially symmetric g ∈ L2. The initial density ρ0 needs not be positive. We also prove some uniqueness results on the strong solutions. Copyright © 2004 John Wiley & Sons, Ltd.
Is the histomorphological concept of the female pelvic floor and its changes due to age and vaginal delivery correct?
Authors: Jundt Katharina , Kiening Marion , Fischer Petra , Bergauer Florian , Rauch Elisabeth , Janni Wolfgang , Peschers Ursula , Dimpfl Thomas
Published: November 2004

Aims

To compare the histomorphology of pelvic floor specimens of 94 female cadavers, ten male cadavers, and 24 female symptomatic patients who underwent pelvic floor surgery, and to evaluate the association of age, parity, and sex to myogenic and/or neurogenic changes to the levator ani muscle (LAM).

Methods

The pelvic floor was biopsied at the pubococcygeus, the iliococcygeus and the coccygeus muscle. After staining, signs for myogenic/neurogenic changes to the muscle were evaluated (fibrosis, variation in fiber diameter, centralization of nuclei, small angulated fibers, and type grouping). To identify the intact neuromuscular junction stainings with NCAM (neuronal cell adhesion molecule) and acetylcholinesterase (ACE) were used.

Results

A significant influence of age and parity on the histomorphological criteria of myogenic cell‐damage was shown in this study. Although these criteria were found even in young nulliparous women, there was a significant increase in older or parous women with at least one vaginal delivery. We failed to demonstrate significant changes between the nulliparous LAM, the male LAM, and the LAM from women with prolapse and incontinence. None of the specimen showed any obvious evidence of neuropathy.

Conclusions

We have evaluated histological criteria adapted from the examination of limb muscles in the LAM of nulliparous young women. “Myogenic changes” seem to be a normal finding in the LAM. The increase of these changes with aging and parity points to mechanical stress to the LAM as the most plausible causative factor. We propose that further studies using histomorphological techniques of the pelvic floor muscle in nulliparous and parous women should clarify the potential role of our histological findings. © 2004 Wiley‐Liss, Inc.
A review on thermal decomposition and combustion of thermoplastic polyesters
Authors: Levchik Sergei V. , Weil Edward D.
Published: November 2004

An overview is presented of the literature on the thermal decomposition and combustion of thermoplastic polyesters, especially commercially important poly(ethylene terephthalate) (PET) and poly(1,4‐butylene terephthalate) (PBT). Although the literature is not clear as to whether heterolytic or homolytic scission of aliphatic fragments is the first step in the thermal decomposition of polyesters, in any case volatilization of light aliphatic fragments make polyesters easily ignitable polymers. Despite the presence of benzene groups in the main polymer chain, thermoplastic polyesters show very limited tendency to char, but instead, aromatic‐containing polymer fragments volatilize and feed the flame. Fire retardant additives, although they usually facilitate decomposition of the polyesters at lower temperature, also usually promote charring and therefore suppress combustion. Copyright © 2004 John Wiley & Sons, Ltd.
Syngenetic permafrost growth: cryostratigraphic observations from the CRREL tunnel near Fairbanks, Alaska
Authors: Shur Y. , French H. M. , Bray M. T. , Anderson D. A.
Published: November 2004

Syngenetic permafrost forms when alluvial, aeolian and/or colluvial sediment accumulates under cold‐climate conditions. Observations from within the CRREL permafrost tunnel near Fairbanks, Alaska, indicate that layered, lenticular‐layered and micro‐lenticular cryogenic structures are characteristic of this type of permafrost. In contrast, reticulate cryogenic structures indicate local thaw modification. During the growth of syngenetic permafrost, episodes of thermokarst erosion may operate preferentially along ice wedges leading to the development of gullies and tunnels in the near‐surface sediments. The local thaw unconformities that result are inferred by the recognition of thermokarst‐cave ice (‘pool’ ice), and various soil and ice pseudomorphs. These may be regarded as further characteristics of syngenetic permafrost growth. Copyright © 2004 John Wiley & Sons, Ltd.
Moisture content measurements of moss (Sphagnum spp.) using commercial sensors
Authors: Yoshikawa Kenji , Overduin Pier Paul , Harden Jennifer W.
Published: November 2004

Sphagnum (spp.) is widely distributed in permafrost regions around the arctic and subarctic. The moisture content of the moss layer affects the thermal insulative capacity and preservation of permafrost. It also controls the growth and collapse history of palsas and other peat mounds, and is relevant, in general terms, to permafrost thaw (thermokarst). In this study, we test and calibrate seven different soil moisture sensors for measuring the moisture content of Sphagnum moss under laboratory conditions. The soil volume to which each probe is sensitive is one of the important parameters influencing moisture measurement, particularly in a heterogeneous medium such as moss.

Each sensor has a unique response to changing moisture content levels, solution salinity, moss bulk density and to the orientation (structure) of the Sphagnum relative to the sensor. All of the probes examined here require unique polynomial calibration equations to obtain moisture content from probe output. We provide polynomial equations for dead and live Sphagnum moss (R2>0.99). Copyright © 2004 John Wiley & Sons, Ltd.
Development of transverse ridges on rock glaciers: field measurements and laboratory experiments
Authors: Kääb A. , Weber M.
Published: November 2004

Very high‐resolution photogrammetric and geodetic measurements about the deformation of transverse ridges on Murtèl, Muragl and Suvretta rock glaciers in the Swiss Alps are discussed. The ridges are advected downstreams with a speed that equals the overall speed of the creeping permafrost within the significance level of the applied techniques. Any process of ridge formation is, thus, overlain on the mass creep. In fact, measurements yield local speed maxima on top of the ridges that can be explained by differential movement due to ridge growth through bulging under compressive flow. This hypothesis is consistent with results from laboratory experiments that were performed on a model ramp employing mixtures of Xanthan Gum, sand and gravel. Indications were also found that overthrusting is involved in the development of transverse ridges on rock glaciers. Copyright © 2004 John Wiley & Sons, Ltd.
Ice segregation and gas distribution in permafrost using tomodensitometric analysis
Authors: Calmels Fabrice , Allard Michel
Published: November 2004

Ice lenses, soil layers, faults, sedimentary structures and gas bubbles in permafrost cores were imaged using a computed tomography scanner. Two kinds of images were produced: two‐dimensional sections which allow ice, gases and soil volumetric contents to be measured, and virtual three‐dimensional reconstructions of the entire core. Volumetric ice and gas contents were measured at 60% and 2% respectively. Ice and gas contents appear to be independent of each other along the stratigraphic profile. The shape and spatial distribution of gaseous inclusions in the permafrost provide some clues on gas source and on the thermo‐mechanics of ice segregation during permafrost aggradation. Copyright © 2004 John Wiley & Sons, Ltd.
Beyond chloride transport: CFTR in the 21st century—introductory remarks to a new state of the art series
Authors: Mehta Anil , Bush Andrew
Published: November 2004

This new series of articles on cystic fibrosis provides an overview of the confusing plethora of problems that arise from the loss of function in a low abundance protein, the cystic fibrosis membrane conductance regulator CFTR. The references are designed to take the clinical reader into areas and journals that they might not normally read. In particular we have concentrated on recent advances that suggest CFTR has functions that do not relate to chloride transport alone. In forthcoming issues of the journal the topics covered range from prospects and difficulties in the translation of new therapies into clinical practice, the regulation of the defective gene (promoters, enhancers, silencers, etc.), regulation and interaction of the CFTR protein product with other proteins in the cell, to functional approaches using developmental and secretory paradigms. These themes have been chosen to bring controversies at the cutting edge of cystic fibrosis research to the practicing pulmonologist in order to stimulate lateral thinking, which we hope will ultimately benefit our patients. Pediatr Pulmonol. 2005; 39:289–291. © 2004 Wiley‐Liss, Inc.