bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneous Catalysis in Supercritical Media: 2. Near‐Critical and Supercritical Water
Authors: Kruse A. , Vogel H.
Published: July 2008

It was demonstrated in part I, also published in this journal, that supercritical carbon dioxide may be advantageous for the use as a reaction medium in heterogeneously catalyzed reactions. Due to its miscibility with hydrogen, hydrogenations of increased selectivity can be carried out or carbonization of catalysts can be reduced by the dissolution and removal of coke precursors. The drawback of supercritical H2O (Tcrit = 374 °C) as compared to supercritical CO2 (Tcrit = 31 °C) is its relatively high critical point. At these temperatures, organic substances decompose within minutes. Consequently, many reactions are carried out below this critical point, in the so‐called “near‐critical water” or “hot compressed water.” Reaction conditions in near‐critical and supercritical water are also referred to as “hydrothermal.” In spite of the relatively high pressures and temperatures required and the associated high experimental expenditure, many types of reactions have already been studied, as the strong dependence of physical and chemical properties on pressure and temperature makes near‐critical and supercritical water a unique and extraordinary solvent.
The geometry of ASCA
Authors: Smilde Age K. , Hoefsloot Huub. C.J. , Westerhuis Johan. A.
Published: July 2008

For analyzing designed high‐dimensional data, no standard methods are currently available. A method that is becoming more and more popular for analyzing such data is ASCA. The mathematics of ASCA are already described elsewhere but a geometrical interpretation is still lacking. The geometry can help practitioners to understand what ASCA does and the more advanced user can get insight into the properties of the method. This paper shows the geometry of ASCA in both the row‐ and column‐space of the matrices involved. Copyright © 2008 John Wiley & Sons, Ltd.
A New Aptameric Biosensor for Cocaine Based on Surface‐Enhanced Raman Scattering Spectroscopy
Authors: Chen Jiwei , Jiang Jianhui , Gao Xing , Liu Guokun , Shen Guoli , Yu Ruqin
Published: July 2008

The present study reports the proof of principle of a reagentless aptameric sensor based on surface‐enhanced Raman scattering (SERS) spectroscopy with “signal‐on” architecture using a model target of cocaine. This new aptameric sensor is based on the conformational change of the surface‐tethered aptamer on a binding target that draws a certain Raman reporter in close proximity to the SERS substrate, thereby increasing the Raman scattering signal due to the local enhancement effect of SERS. To improve the response performance, the sensor is fabricated from a cocaine‐templated mixed self‐assembly of a 3′‐terminal tetramethylrhodamine (TMR)‐labeled DNA aptamer on a silver colloid film by means of an alkanethiol moiety at the 5′ end. This immobilization strategy optimizes the orientation of the aptamer on the surface and facilitates the folding on the binding target. Under optimized assay conditions, one can determine cocaine at a concentration of 1 μM, which compares favorably with analogous aptameric sensors based on electrochemical and fluorescence techniques. The sensor can be readily regenerated by being washed with a buffer. These results suggest that the SERS‐based transducer might create a new dimension for future development of aptameric sensors for sensitive determination in biochemical and biomedical studies.
Uniform Metal (Hydr)Oxide Particles from Water/Ionic Liquid Precursor (ILP) Mixtures
Authors: Li Zhonghao , Rabu Pierre , Strauch Peter , Mantion Alexandre , Taubert Andreas
Published: July 2008

We have recently shown that the hydrated ionic liquid tetrabutylammonium hydroxide (TBAH) is an efficient ionic liquid precursor (ILP) for the fabrication of ZnO/carbohydrate materials (D. Mumalo‐Djokic, W. B. Stern, A. Taubert, Cryst. Growth Des. 2008, 8, 330). The current paper shows that ZnO is just one example out of the large group of technologically important metal (hydr)oxides that can be made using TBAH. Simply by using different metal acetates as precursors in TBAH, it is possible to make a wide variety of metal (hydr)oxides with well‐defined size, morphology, and chemical composition. It is also possible to dope metal oxide particles or to synthesize mixed metal oxide particles, and therefore to control properties like magnetism.
Magnetic Endohedral Transition‐Metal‐Doped Semiconduncting‐Nanoclusters
Authors: Matxain Jon M. , Formoso Elena , Mercero Jose M. , Piris Mario , Lopez Xabier , Ugalde Jesus M.
Published: July 2008

Endohedral first‐row transition‐metal‐doped TM@ZniSi nanoclusters, in which TM stands for the first‐row transition‐metals from Sc to Zn, and i=12, 16, have been characterized. In these structures the dopant metals are trapped inside spheroidal hollow semiconducting nanoclusters. It is observed that some of the transition metals are trapped in the center of mass of the cluster, whereas others are found to be displaced from that center, leading to structures in which the transition metals display a complex dynamical behavior upon encapsulation. This fact was confirmed by quantum molecular dynamics calculations, which further confirmed the thermal stability of endohedral compounds. In the endohedrally‐doped nanoclusters in which the transition‐metal atom sits on the center of mass, the host hollow cluster structure remains undistorted after dopant encapsulation. Conversely, if the encapsulated transition‐metal atom is displaced from the center of mass, the host hollow cluster structure suffers a very tiny distortion. Additionally, it is found that there is negligible charge transfer between the dopant transition‐metal atom and its hollow cluster host and, after encapsulation, the spin densities remain localized on the transition‐metal atom. This allows for the atomic‐like behavior of the trapped transition‐metal atom, which gives rise to their atomic‐like magnetic properties. The encapsulation free energies are negative, suggesting that these compounds are thermodynamically stable.
Functionalized Supramolecular Nanoporous Arrays for Surface Templating
Authors: Perdigão Luís M. A. , Saywell Alex , Fontes Giselle N. , Staniec Paul A. , Goretzki Gudrun , Phillips Anna G. , Champness Neil R. , Beton Peter H.
Published: July 2008

Controlled self‐assembly and chemical tailoring of bimolecular networks on surfaces is demonstrated using structural derivatives of 3,4:9,10‐perylenetetracarboxylic diimide (PTCDI) combined with melamine (1,3,5‐triazine‐2,4,6‐triamine). Two functionalised PTCDI derivatives have been synthesised, Br2–PTCDI and di(propylthio)–PTCDI, through attachment of chemical side groups to the perylene core. Self‐assembled structures formed by these molecules on a Ag–Si(111)${\sqrt{3}}$×${\sqrt{3}}$R30° surface were studied with a room‐temperature scanning tunneling microscope under ultrahigh vacuum conditions. It is shown that the introduction of side groups can have a significant effect upon both the structures formed, notably in the case of di(propylthio)–PTCDI which forms a previously unreported unimolecular hexagonal arrangement, and their entrapment behaviour. These results demonstrate a new route of functionalisation for network pores, opening up the possibility of designing nanostructured surface structures with chemical selectivity and applications in nanostructure templating.
Combining G‐Quadruplex Targeting Motifs on a Single Peptide Nucleic Acid Scaffold: A Hybrid (3+1) PNA–DNA Bimolecular Quadruplex
Authors: Paul Alexis , Sengupta Poulami , Krishnan Yamuna , Ladame Sylvain
Published: July 2008

We describe the first G‐quadruplex targeting approach that combines intercalation and hybridization strategies by investigating the interaction of a G‐rich petide nucleic acid (PNA) acridone conjugate 1 with a three‐repeat fragment of the human telomere G 3 to form a hybrid PNA–DNA quadruplex that mimicks the biologically relevant (3+1) pure DNA dimeric telomeric quadruplex. Using a combination of UV and fluorescence spectroscopy, circular dichroism (CD), and mass‐spectrometry, we show that PNA 1 can induce the formation of a bimolecular hybrid quadruplex even at low salt concentration upon interaction with a single‐stranded three‐repeat fragment of telomeric DNA. However, PNA 1 cannot invade a short fragment of B‐DNA even if the latter contains a CCC motif complementary to the PNA sequence. These studies could open up new possibilities for the design of a novel generation of quadruplex ligands that target not only the external features of the quadruplex but also its central core constituted by the tetrads themselves.
Intermolecular Alkene and Alkyne Hydroacylation with β‐S‐Substituted Aldehydes: Mechanistic Insight into the Role of a Hemilabile P–O–P Ligand
Authors: Moxham Gemma L. , Randell‐Sly Helen , Brayshaw Simon K. , Weller Andrew S. , Willis Michael C.
Published: July 2008

A straightforward to assemble catalytic system for the intermolecular hydroacylation reaction of β‐S‐substituted aldehydes with activated and unactivated alkenes and alkynes is reported. These catalysts promote the hydroacylation reaction between β‐S‐substituted aldehydes and challenging substrates, such as internal alkynes and 1‐octene. The catalysts are based upon [Rh(cod)(DPEphos)][ClO4] (DPEphos=bis(2‐diphenylphosphinophenyl)ether, cod=cyclooctadiene) and were designed to make use of the hemilabile capabilities of the DPEphos ligand to stabilise key acyl–hydrido intermediates against reductive decarbonylation, which results in catalyst death. Studies on the stoichiometric addition of aldehyde (either ortho‐HCOCH2CH2SMe or ortho‐HCOC6H4SMe) and methylacrylate to precursor acetone complexes [Rh(acetone)2(DPEphos)][X] [X=closo‐CB11H6Cl6 or [BArF4] (ArF = 3,5‐(CF3)2C6H3)] reveal the role of the hemilabile DPEphos ligand. The crystal structure of [Rh(acetone)2(DPEphos)][X] shows a cis‐coordinated diphosphine ligand with the oxygen atom of the DPEphos distal from the rhodium. Addition of aldehyde forms the acyl hydride complexes [Rh(DPEphos)(COCH2CH2SMe)H][X] or [Rh(DPEphos)(COC6H4SMe)H][X], which have a trans‐spanning DPEphos ligand and a coordinated ether group. Compared to analogous complexes prepared with dppe (dppe=1,2‐bis(diphenylphosphino)ethane), these DPEphos complexes show significantly increased resistance towards reductive decarbonylation. The crystal structure of the reductive decarbonylation product [Rh(CO)(DPEphos)(EtSMe)][closo‐CB11H6I6] is reported. Addition of alkene (methylacrylate) to the acyl–hydrido complexes forms the final complexes [Rh(DPEphos)(η1‐MeSC2H4‐η1‐COC2H4CO2Me)][X] and [Rh(DPEphos)(η1‐MeSC6H4‐η1‐COC2H4CO2Me)][X], which have been identified spectroscopically and by ESIMS/MS. Intermediate species in this transformation have been observed and tentatively characterised as the alkyl–acyl complexes [Rh(CH2CH2CO2Me)(COC2H4SMe)(DPEphos)][X] and [Rh(CH2CH2CO2Me)(COC6H4SMe)(DPEphos)][X]. In these complexes, the DPEphos ligand is now cis chelating. A model for the (unobserved) transient alkene complex that would result from addition of alkene to the acyl–hydrido complexes comes from formation of the MeCN adducts [Rh(DPEphos)(MeSC2H4CO)H(MeCN)][X] and [Rh(DPEphos)(MeSC6H4CO)H(MeCN)][X]. Changing the ligand from DPEphos to one with a CH2 linkage, [Ph2P(C6H4)]2CH2, gave only decomposition on addition of aldehyde to the acetone precursor, which demonstrated the importance of the hemiabile ether group in DPEphos. With [Ph2P(C6H4)]2S, the sulfur atom has the opposite effect and binds too strongly to the metal centre to allow access to productive acetone intermediates.
Textural Manipulation of Mesoporous Materials for Hosting of Metallic Nanocatalysts
Authors: Sun Junming , Bao Xinhe
Published: July 2008

The preparation and stabilization of nanoparticles are becoming very crucial issues in the field of so‐called “nanocatalysis”. Recent developments in supramolecular self‐assembled porous materials have opened a new way to get nanoparticles hosted in the channels of such materials. In this paper, a new approach towards monodisperse and thermally stable metal nanoparticles by confining them in ordered mesoporous materials is presented, and three aspects are illustrated. Firstly, the recent progress in the functional control of mesoporous materials will be briefly introduced, and the rational tuning of the textures, pore size, and pore length is demonstrated by controlling supramolecular self‐assembly behavior. A novel synthesis of short‐pore mesoporous materials is emphasized for their easy mass transfer in both biomolecule absorption and the facile assembly of metal nanocomposites within their pore channels. In the second part, the different routes for encapsulating monodisperse nanoparticles inside channels of porous materials are discussed, which mainly includes the ion‐exchange/conventional incipient wetness impregnation, in situ encapsulation routes, organometallic methodologies, and surface functionalization schemes. A facile in situ autoreduction route is highlighted to get monodisperse metal nanoparticles with tunable sizes inside the channels of mesoporous silica. Finally, confinement of mesoporous materials is demonstrated to improve the thermal stability of monodisperse metal nanoparticles catalysts and a special emphasis will be focused on the stabilization of the metal nanoparticles with a low Tammann temperature. Several catalytic reactions concerning the catalysis of nanoparticles will be presented. These uniform nanochannels, which confine monodisperse and stable metal nanoparticles catalysts, are of great importance in the exploration of size‐dependent catalytic chemistry and further understanding the nature of catalytic reactions.
Folate‐Equipped Pegylated Archaeal Lipid Derivatives: Synthesis and Transfection Properties
Authors: Lainé Céline , Mornet Emmanuel , Lemiègre Loïc , Montier Tristan , Cammas‐Marion Sandrine , Neveu Cécile , Carmoy Nathalie , Lehn Pierre , Benvegnu Thierry
Published: July 2008

We have previously shown that synthetic archaeal lipid analogues are useful vectors for drug/gene delivery. We report herein the synthesis and gene transfer properties of a series of novel di‐ and tetraether‐type archaeal derivatives with a poly(ethylene glycol) (PEG) chain and further equipped with a folic acid (FA) group. The synthetic strategy and the purification by dialysis ensured complete removal of free FA. The lipids were mixed with a conventional glycine betaine‐based cationic lipid and the resulting formulations were tested in transfection assays after complexation with plasmid DNA. All four novel co‐lipids afforded efficient in vitro gene transfection. Moreover, the FA‐equipped derivatives permitted ligand/receptor‐based targeted transfection; their activity was inhibited when free FA was added to the transfection medium. These novel archaeal derivatives equipped with FA‐PEG moieties may thus be of great interest for targeted in vivo transfection.
A Simple and Efficient Strategy To Enhance the Antioxidant Activities of Amino‐Substituted Glutathione Peroxidase Mimics
Authors: Bhabak Krishna P. , Mugesh Govindasamy
Published: July 2008

The glutathione peroxidase (GPx) activities of some diaryl diselenides incorporating tertiary amino groups were studied with H2O2, Cum‐OOH, and tBuOOH as substrates and with PhSH as thiol co‐substrate. Simple replacement of a hydrogen atom with a methoxy group dramatically enhances the GPx activity. The introduction of methoxy substituents ortho to selenium in N,N‐dialkylbenzylamine‐based compounds makes the basicity of the amino groups perfect for the catalysis. The presence of 6‐OMe groups prevents possible Se⋅⋅⋅N interactions in the selenols, increasing their zwitterionic characters. The methoxy substituents also protect the selenium in the selenenic acid intermediates from overoxidation to seleninic acids or irreversible inactivation to selenonic acid derivatives. The additional substituents also play a crucial role in the selenenyl sulfide intermediates, by preventing thiol exchange reactions—which would normally lead to an inactivation pathway—at the selenium centers. The strengths of Se⋅⋅⋅N interactions in the selenenyl sulfide intermediates are dramatically reduced upon introduction of the methoxy substituents, which not only reduce the thiol exchange reactions at selenium but also enhance the nucleophilic attack of the incoming thiols at sulfur. The facile attack of thiols at sulfur in the selenenyl sulfides also prevents the reactions between the selenenyl sulfides and H2O2 that can regenerate the selenenic acids (reverse‐GPx cycle). These studies reveal that the simple 6‐OMe groups play multiple roles in each of the catalytically active intermediates by introducing steric and electronic effects that are required for efficient catalysis.
TEMPO Supported on Magnetic C/Co‐Nanoparticles: A Highly Active and Recyclable Organocatalyst
Authors: Schätz Alexander , Grass Robert N. , Stark Wendelin J. , Reiser Oliver
Published: July 2008

TEMPO was grafted on graphene‐coated nanobeads with a magnetic cobalt core by using a general applicable “click”‐chemistry protocol. The new heterogeneous CoNP–TEMPO emerged as a highly active catalyst for the chemoselective oxidation of primary and secondary alcohols using bleach as terminal oxidant. The outstanding stability of the C/Co nanoparticles enables the nanopowder to tolerate several TEMPO‐mediated iterative oxidation reactions without any significant loss in catalyst activity. Furthermore, the excellent magnetic properties enable the rapid separation and quantitative recycling of CoNP–TEMPO out of the reaction mixture by simple magnetic decantation. The recovered nanoparticles can be subsequently reused without any further purification.
Pt@MOF‐177: Synthesis, Room‐Temperature Hydrogen Storage and Oxidation Catalysis
Authors: Proch Sebastian , Herrmannsdörfer Justus , Kempe Rhett , Kern Christoph , Jess Andreas , Seyfarth Lena , Senker Jürgen
Published: July 2008

The gas‐phase loading of [Zn4O(btb)2]8 (MOF‐177; H3btb=1,3,5‐benzenetribenzoic acid) with the volatile platinum precursor [Me3PtCp′] (Cp′=methylcyclopentadienyl) was confirmed by solid state 13C magic angle spinning (MAS)‐NMR spectroscopy. Subsequent reduction of the inclusion compound [Me3PtCp′]4@MOF‐177 by hydrogen at 100 bar and 100 °C for 24 h was carried out and gave rise to the formation of platinum nanoparticles in a size regime of 2–5 nm embedded in the unchanged MOF‐177 host lattice as confirmed by transmission electron microscopy (TEM) micrographs and powder X‐ray diffraction (PXRD). The room‐temperature hydrogen adsorption of Pt@MOF‐177 has been followed in a gravimetric fashion (magnetic suspension balance) and shows almost 2.5 wt % in the first cycle, but is decreased down to 0.5 wt % in consecutive cycles. The catalytic activity of Pt@MOF‐177 towards the solvent‐ and base‐free room temperature oxidation of alcohols in air has been tested and shows Pt@MOF‐177 to be an efficient catalyst in the oxidation of alcohols.
Assessing Synthetic Strategies: Total Syntheses of (±)‐Neodolabellane‐Type Diterpenoids
Authors: Valente Cory , Organ Michael G.
Published: July 2008

Two strategies, namely a cross‐metathesis/ring‐closing metathesis and Pd‐catalyzed Stille allylation/Nozaki–Hiyama–Kishi coupling, are examined for the preparation of neodolabellane‐type diterpenoids 1 and 2. Whereas the first approach possessed synthetic limitations, the latter was successfully employed to provide compounds 1 and 2 in 8.8 % (14 steps) and 8 % (15 steps) overall yields, respectively.
Structure–Activity Relationships of Phenylalkylamines as Agonist Ligands for 5‐HT2AReceptors
Authors: Blaazer Antoni R. , Smid Pieter , Kruse Chris G.
Published: July 2008

Agonist activation of central 5‐HT2Areceptors results in diverse effects, such as hallucinations and changes of consciousness. Recent findings indicate that activation of the 5‐HT2Areceptor also leads to interesting physiological responses, possibly holding therapeutic value. Selective agonists are needed to study the full therapeutic potential of this receptor. 5‐HT2Aligands with agonist profiles are primarily derived from phenylalkylamines, indolealkylamines, and certain piperazines. Of these, phenylalkylamines, most notably substituted phenylisopropylamines, are considered the most selective agonists for 5‐HT2receptors. This review summarizes the structure–activity relationships (SAR) of phenylalkylamines as agonist ligands for 5‐HT2Areceptors. Selectivity is a central theme, as is selectivity for the 5‐HT2Areceptor and for its specific signaling pathways. SAR data from receptor affinity studies, functional assays, behavioral drug discrimination as well as human studies are discussed.
Distribution of voltage‐gated potassium and hyperpolarization‐activated channels in sensory afferent fibers in the rat carotid body
Authors: Buniel Maria , Glazebrook Patricia A. , Ramirez‐Navarro Angelina , Kunze Diana L.
Published: July 2008

The chemosensory glomus cells of the carotid body (CB) detect changes in O2 tension. Carotid sinus nerve fibers, which originate from peripheral sensory neurons located within the petrosal ganglion, innervate the CB. Release of transmitter from glomus cells activates the sensory afferent fibers to transmit information to the nucleus of the solitary tract in the brainstem. The ion channels expressed within the sensory nerve terminals play an essential role in the ability of the terminal to initiate action potentials in response to transmitter‐evoked depolarization. However, with a few exceptions, the identity of ion channels expressed in these peripheral nerve fibers is unknown. This study addresses the expression of voltage‐gated channels in the sensory fibers with a focus on channels that set the resting membrane potential and regulate discharge patterns. By using immunohistochemistry and fluorescence confocal microscopy, potassium channel subunits and HCN (hyperpolarization‐activated) family members were localized both in petrosal neurons that expressed tyrosine hydroxylase and in the CSN axons within the carotid body. Channels contributing to resting membrane potential, including HCN2 responsible in part for Ih current and the KCNQ2 and KCNQ5 subunits thought to underlie the neuronal “M current,” were identified in the sensory neurons and their axons innervating the carotid body. In addition, the results presented here demonstrate expression of several potassium channels that shape the action potential and the frequency of discharge, including Kv1.4, Kv1.5, Kv4.3, and KCa (BK). The role of these channels should be considered in interpretation of the fiber discharge in response to perturbation of the carotid body environment. J. Comp. Neurol. 510:367–377, 2008. © 2008 Wiley‐Liss, Inc.
Solvent as a Probe of Active Site Motion and Chemistry during the Hydrogen Tunnelling Reaction in Morphinone Reductase
Authors: Hay Sam , Pudney Christopher R. , Sutcliffe Michael J. , Scrutton Nigel S.
Published: July 2008

The reductive half‐reaction of morphinone reductase involves a hydride transfer from enzyme‐bound β‐nicotinamide adenine dinucleotide (NADH) to a flavin mononucleotide (FMN). We have previously demonstrated that this step proceeds via a quantum mechanical tunnelling mechanism. Herein, we probe the effect of the solvent on the active site chemistry. The pKa of the reduced FMN N1 is 7.4±0.7, based on the pH‐dependence of the FMN midpoint potential. We rule out that protonation of the reduced FMN N1 is coupled to the preceding H‐transfer as both the rate and temperature‐dependence of the reaction are insensitive to changes in solution pH above and below this pKa. Further, the solvent kinetic isotope effect is ∼1.0 and both the 1° and 2° KIEs are insensitive to solution pH. The effect of the solvent’s dielectric constant is investigated and the rate of H‐transfer is found to be unaffected by changes in the dielectric constant between ∼60 and 80. We suggest that, while there is crystallographic evidence for some water in the active site, the putative promoting motion involved in the H‐tunnelling reaction is insensitive to such changes.
A linearly adaptive gate drive technique for light‐load efficiency improvement of DC–DC converters
Authors: Liu Pang‐Jung , Chen Yi‐Jan Emery
Published: July 2008

This paper presents a linearly adaptive gate drive technique to improve the light‐load efficiency of DC–DC converters. The optimal‐driving voltages of the power MOSFETs for reducing gate‐driving loss can be well modeled by a linear function of the load current. By scaling the gate drive voltage dynamically with respect to load current, the light‐load efficiency can be enhanced. The experimental result shows that the proposed gate drive technique can attain about 9% incremental light‐load efficiency enhancement. Copyright © 2008 John Wiley & Sons, Ltd.
Insulin: moments in history
Authors: Rendell Marc
Published: July 2008

The isolation of insulin by Banting and Best in 1922 was a historic event of life‐saving importance. Thousands of individuals doomed to die of type I diabetes were saved. The inspiring story of insulin continued to grow and evolve with the development of PZI, NPH, and lente insulins. The advent of production of human insulin from recombinant DNA brought an end to the extraction of insulin from animal pancreas. Modification of the amino acid sequences of insulin led to new forms of fast‐acting insulin, such as lispro, aspart, and glulisine, and to long‐acting insulins like glargine and detemir. The technology of insulin pumps advanced from large, cumbersome equipment to present‐day devices no bigger than a hand calculator. The accuracy of implantable glucose sensors improved progressively, culminating in the approval of devices that will soon exert reliable feedback control of insulin pumps. Transplantation of the pancreas offers a cure for type I diabetes, and the development of islet cell transplantation continues. It is now appreciated that islet cells regenerate in the normal pancreas, and islet cell neogenesis agents have been identified and may eventually contribute to the reversal of diabetes. Drug Dev Res 69:95–100, 2008. ©2008 Wiley‐Liss, Inc.
Mechanisms of β cell failure in the pathogenesis of Type 2 diabetes
Authors: Accili Domenico
Published: July 2008

β cell failure plays a key role in the pathogenesis of type 2 diabetes. It consists of impaired insulin secretion and decreased β cell mass. Recent insight into the pathogenesis of diabetes‐associated β cell failure has shown that (1) β cell compensation to insulin resistance occurs primarily via increased β cell replication; (2) commonly employed diabetes treatments are associated with a seemingly irreversible loss of β cell function; and (3) most diabetes‐associated genes identified in recent genome‐wide association studies appear to regulate β cell mass and/or function, as opposed to insulin action. Experimental studies in animal models have contributed to establishing the idea that pancreatic β cells are an “insulin target tissue,” in which insulin signaling links insulin secretion with cellular proliferation and survival. It is possible that β cell failure represents but another aspect of insulin resistance. Prevention of β cell dysfunction is a critical goal of diabetes therapy, and it will require the identification of “druggable” cellular pathways that can be enlisted in the clinic to achieve durability of treatment. Drug Dev Res 69:111–115, 2008 © 2008 Wiley‐Liss, Inc.
Initiating insulin in type 2 diabetes
Authors: Dailey George
Published: July 2008

There are a variety of oral hypoglycemic agents available for use in type 2 diabetes. Despite the increasing choices of oral agents, insulin therapy remains the most effective means to lower blood glucose and often must be used. There is some controversy as to the best approach to the initiation of insulin treatment in type 2 diabetes. The approach we favor begins with basal insulin with later addition of premeal rapid‐acting insulin. Drug Dev Res 69:116–118, 2008. © 2008 Wiley‐Liss, Inc.
Insulin treatment of post‐prandial hyperglycemia
Authors: Rendell Marc S.
Published: July 2008

With evidence that elevated post‐prandial glucose (PPG) is a major risk factor for cardiovascular disease, there is increasing emphasis on primary treatment of PPG in diabetes. The carbohydrate content of a meal is the principal contribution to PPG, so efforts to reduce carbohydrate ingestion are an important dietary approach to management. Although all oral hypoglycemics reduce PPG, newer agents including disaccharidase inhibitors and meglitinides act more selectively to lower PPG. GLP‐1 agonists and pramlintide act primarily on post‐meal glucose. DPP‐IV inhibitors are oral agents that raise GLP‐1 levels. Unquestionably, exogenous insulin is the most potent agent to lower PPG levels. Long‐acting basal insulin has much less effect on PPG than rapid‐acting insulin taken at the time of a meal. Inhaled insulin is no more effective than injectable insulin but is much more acceptable to most patients and may thus lead to administration of insulin earlier in the course of type II diabetes. Drug Dev Res 69:124–129, 2008. © 2008 Wiley‐Liss, Inc.
Prandial insulin: is inhaled enough?
Authors: Boss Anders H. , Yu Wen , Ellerman Karen
Published: July 2008

The low proportion of patients achieving glycemic targets is well documented for both type 1 and type 2 diabetes. Postprandial glucose levels are often not monitored but contribute significantly to total glycemic burden. Prandial rapid‐acting insulin analogues were introduced to address some of these problems but still do not provide a physiologic insulin replacement. Inhaled prandial insulins have been developed to free patients from multiple mealtime injections and make intensive insulin regimens more acceptable. Several inhaled formulations of prandial insulin are in development but differ significantly with respect to inhaler characteristics and pharmacokinetic profiles. This brief review summarizes the properties of the new prandial inhaled insulins and discusses how postprandial glycemic control is dependent not only on the insulin dose, but also on the pharmacokinetic characteristics of insulin delivery. There is no antihyperglycemic agent with a glucose‐lowering effect superior to that of insulin; new prandial products that improve coordination between insulin availability and meal absorption and are more acceptable to patients may increase the proportion of diabetic patients achieving and maintaining glycemic targets. Drug Dev Res 69:138–142, 2008. © 2008 Wiley‐Liss, Inc.
Treatment of type 1 diabetes in children and adolescents
Authors: Desmangles Jean‐Claude
Published: July 2008

Despite the recent advances in treatment and technology, intensive insulin therapy for treatment of type 1 diabetes remains a challenge in children due to developmental issues, wide glycemic fluctuations and unpredictable eating and activity patterns. Many children with diabetes nowadays use a basal‐bolus regimen by means of either multiple daily injections or CSII in an attempt to mimic closely the physiological insulin and serum glucose profiles in order to achieve optimal glycemic control. This article reviews the different regimens employed to treat type 1 diabetes in children, using short‐ and intermediate‐acting insulins, newer insulin analogues, as well as continuous subcutaneous insulin infusion (CSII). With the ongoing development of new technologies allowing better monitoring of blood glucose and insulin delivery, it is hoped that in the near future a “closed loop system” will help in achieving normal glycemic control while minimizing side effects related to administration of exogenous insulin. Drug Dev Res 69:158–164, 2008. © 2008 Wiley‐Liss, Inc.
Transplantation and beyond
Authors: Taylor‐Fishwick David A. , Pittenger Gary L. , Vinik Aaron I.
Published: July 2008

The pathophysiology of diabetes, either type 1 or type 2, involves the loss of β cell mass to a point where there is insufficient insulin secretion to meet the body's needs. The overall loss of β cells results from β cell destruction in conjunction with a failure of physiological regulators to restore or regenerate the β cell population. Historically, therapy for diabetes has been limited to efforts to control hyperglycemia and to prevent and/or ameliorate the complications associated with diabetes. Multiple approaches to repopulate the diabetic pancreas with functional islets have been proposed, including whole pancreas transplantation with or without a kidney, direct islet transplantation from cadaveric donors, generation of artificial islets, and development of new islets from stem cells. Ex vivo differentiation of embryonic stem cells offers great attraction as an alternative islet source but, to date, fully functional islets have not been developed. An alternative approach is to target stem cells present in the adult pancreas. Stimulation of these cells with various factors offers the hope of promoting differentiation to functional islets. Islet neogenesis‐associated peptide (INGAP) is one such factor. INGAP treatment has reversed insulin‐dependent diabetes in a mouse model. INGAP treatment has elicited production of C‐peptide in insulin‐dependent diabetic patients. Future approaches may combine INGAP with immunosuppression in an attempt to reverse type 1 diabetes. Drug Dev Res 69:165–176, 2008 © 2008 Wiley‐Liss, Inc.
Intranasal insulin: PK profile designed specifically for prandial treatment of Type 2 Diabetes
Authors: Mitchell Richard L. , Costantino Henry R. , Sileno Anthony , Duffy Timothy , Brandt Gordon , Quay Steven C.
Published: July 2008

Insulin is the most effective therapy for lowering glycosylated hemoglobin (A1c) levels in Type 2 diabetics, and yet it is typically the last therapeutic option employed. Currently, the vast majority of marketed prandial insulin products require frequent injections, which may be a barrier among patients and physicians to initiating this medically important therapy. Beyond the inconvenience, concerns about potential weight gain and hypoglycemia may also limit the early use of insulin therapy. None of the approved insulin formulations (including rapid‐acting products) provide a PK response fast enough to mimic the endogenous first‐phase insulin release that is seen following bolus intravenous glucose infusion and that is associated with downregulation of gluconeogenesis. Delayed absorption of insulin from subcutaneous injection results in a relatively broad plasma insulin peak and a prolonged duration of action, potentially increasing the risk of hypoglycemia. We are developing an intranasal insulin formulation that provides a well‐tolerated and efficient means of delivering prandial insulin more rapidly than fast‐acting injectable insulin. With its fast onset and short duration of action, Nastech's intranasal insulin exhibits pharmacokinetic and pharmacodynamic properties that take advantage of the known benefits of delivering a rapid and transient burst of insulin at mealtime. This review discusses the current development of intranasal formulations and compares the characteristics of intranasal insulin to other non‐invasive insulin delivery efforts, including pulmonary, oral, and transdermal formulations. Drug Dev Res 69:143–152, 2008. © 2008 Wiley‐Liss, Inc.
Beyond the Icosahedron: A Density Functional Theory Study of 14‐Atom Germanium Clusters
Authors: King R. Bruce , Silaghi‐Dumitrescu Ioan , Uţă Matei M.
Published: July 2008

Density functional theory (DFT) at the hybrid B3LYP level has been applied to the germanium clusters Ge14z (z = –8, –6, –4, –2, 0, +2, +4) starting from seven different initial configurations. An Oh omnicapped cube structure is the most stable for Ge142– followed by a hexagonal antiprism structure with a relative energy of 42.7 kcal/mol. The lowest‐energy structure for neutral Ge14 is a triplet omnicapped cube with full Oh symmetry followed by a singlet omnicapped cube compressed to D4h symmetry through Jahn–Teller distortion. The lowest energy Ge142+ structure is also an Oh structure derived from the omnicapped cube through elongation of the 12 edges of the underlying cube to give a rhomboidal dodecahedron with 12 rhombus faces. The lowest‐energy Ge124+ structure is a bicapped icosahedron. Some D6h hexagonal wheel structures at higher energies are also found for the hypoelectronic systems Ge14, Ge142+, and Ge144+. The lowest‐energy structures for the hyperelectronic Ge144–, Ge146–, and Ge148– are relatively unsymmetrical not readily recognizable open structures typically with some pentagonal or hexagonal faces. The D6d bicapped hexagonal antiprism found in 14‐vertex C2B12 carborane and M2C2B10 dimetallacarborane structures is not the lowest‐energy structure for any of the Ge14z clusters.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Mixed Heterotri‐ to Heteropentametallic Transition‐Metal Complexes: Synthesis, Characterization and Electrochemical Behavior
Authors: Packheiser Rico , Ecorchard Petra , Rüffer Tobias , Walfort Bernhard , Lang Heinrich
Published: July 2008

The synthesis and reaction chemistry of heteromultimetallic transition‐metal complexes are discussed. Complex [(η2‐dppf)(η5‐C5H5)Ru‐C≡C‐C6H4‐4‐PPh2] (3) [dppf = 1,1′‐bis(diphenylphosphanyl)ferrocene], accessible by treating [(η2‐dppf)(η5‐C5H5)RuCl] (1) with equimolar amounts of HC≡C‐C6H4‐4‐PPh2 (2), gives on treatment with [(cod)RhCl]2 (4), [(η5‐C5Me5)RhCl2]2 (6), and [(tht)AuCl] (8) heterotrimetallic [(η2‐dppf)(η5‐C5H5)Ru‐C≡C‐C6H4‐4‐PPh2‐{Rh}] [5, {Rh} = (cod)RhCl; 7, {Rh} = (η5‐C5Me5)RhCl2] and [(η2‐dppf)(η5‐C5H5)Ru‐C≡C‐C6H4‐4‐PPh2‐AuCl] (9), respectively. Tetra‐ and even pentametallic heteronuclear complexes can be prepared by following consecutive reaction sequences: Treatment of 9 with HC≡CR {10a, R = C5H4N‐4; 10b, R = C6H4‐4‐C≡N; 10c, R = bpy (= 2,2′‐bipyridyl‐5‐yl); 12a, R = bpy[Re(CO)3Cl]} in the presence of HNEt2 and [CuI] gave [(η2‐dppf)(η5‐C5H5)Ru‐C≡C‐C6H4‐4‐PPh2‐Au‐C≡CR] {11a, R = C5H4N‐4; 11b, R = C6H4‐4‐C≡N; 11c, R = bpy; 13, R = bpy[Re(CO)3Cl]}. Compound 11c is the key starting material for complexes of higher nuclearity. Treatment of 11c with [(nbd)Mo(CO)4] (14) afforded heterotetrametallic {(η2‐dppf)(η5‐C5H5)Ru‐C≡C‐C6H4‐4‐PPh2‐Au‐C≡C‐bpy[Mo(CO)4]} (15), whereas with [{[Ti](μ‐σ,π‐C≡CSiMe3)2}M]X [16a, MX = Cu(N≡CMe)PF6; 16b, MX = AgOClO3] novel heteropentametallic [(η2‐dppf)(η5‐C5H5)Ru‐C≡C‐C6H4‐4‐PPh2‐Au‐C≡C‐bpy({[Ti](μ‐σ,π‐C≡CSiMe3)2}M)]X (17a, M = Cu, X = PF6; 17b, M = Ag, X = ClO4) is formed. The reaction of 11a with [{[Ti](μ‐σ,π‐C≡CSiMe3)2}Cu]OTf (16c) produced [(η2‐dppf)(η5‐C5H5)Ru‐C≡C‐C6H4‐4‐PPh2‐Au‐C≡C‐4‐C5H4N({[Ti](μ‐σ,π‐C≡CSiMe3)2}Cu)]OTf (18). The structures of 9, 11b, 11c, and 12 in the solid state and the electrochemical behavior of selected complexes are also reported.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Archaeal Lipids: Innovative Materials for Biotechnological Applications
Authors: Benvegnu Thierry , Lemiègre Loïc , Cammas‐Marion Sandrine
Published: July 2008

This microreview focuses on the development of diether‐type and tetraether‐type archaeal lipids as innovative materials for biotechnological applications, with special attention to synthetic analogues as well as to recent natural lipid structures. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Forced Complexation of Nitrogen Leading to a Weakening of Amide Bonds: Application to a New Linker for Solid‐Phase Chemistry
Authors: Bröhmer Manuel C. , Bannwarth Willi
Published: July 2008

Cu2+ complexation of a bispicolylamide entity leads to a weakening of the N–C‐amide bond, which subsequently can be cleaved under very mild conditions by methanolysis. On the basis of this principle we developed a versatile and robust linker for solid‐phase chemistry. The stability of the linker was demonstrated under acidic and basic conditions, and it was evaluated for its utility in peptide synthesis as well as for reductive amination, Pd‐mediated C–C‐coupling, and metathesis reactions.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Application of artificial neural networks to estimate wastewater treatment plant inlet biochemical oxygen demand
Authors: Dogan Emrah , Ates Asude , Yilmaz Ece Ceren , Eren Beytullah
Published: July 2008

Biochemical oxygen demand (BOD) has been shown to be an important variable in water quality management and planning. However, BOD is difficult to measure and needs longer time periods (5 days) to get results. Artificial neural networks (ANNs) are being used increasingly to predict and forecast water resource variables. The objective of this research was to develop an ANNs model to estimate daily BOD in the inlet of wastewater biochemical treatment plants. The plantscale data set (364 daily records of the year 2005) was obtained from a local wastewater treatment plant. Various combinations of daily water quality data, namely chemical oxygen demand (COD), water discharge (Qw), suspended solid (SS), total nitrogen (N), and total phosphorus (P) are used as inputs into the ANN so as to evaluate the degree of effect of each of these variables on the daily inlet BOD. The results of the ANN model are compared with the multiple linear regression model (MLR). Mean square error, average absolute relative error, and coefficient of determination statistics are used as comparison criteria for the evaluation of the model performance. The ANN technique whose inputs are COD, Qw, SS, N, and P gave mean square errors of 708.01, average absolute relative errors of 10.03%, and a coefficient of determination 0.919, respectively. On the basis of the comparisons, it was found that the ANN model could be employed successfully in estimating the daily BOD in the inlet of wastewater biochemical treatment plants. © 2008 American Institute of Chemical Engineers Environ Prog, 2008
Many roads lead to Rome: Why does cognitive behavioural therapy remain unsuccessful for many eating disorder patients?
Authors: Vanderlinden Johan
Published: July 2008

This paper makes the case that the widely used evidence‐based ‘CBT’ approaches remain unsuccessful in many eating disorder patients. Six critical ‘personal reflections’ are formulated on why many patients remain totally resistant toward our therapeutic endeavours. My reflections suggest that probably many roads may lead to Rome. Copyright © 2008 John Wiley & Sons, Ltd and Eating Disorders Association.
An implementation of the Spalart–Allmaras DES model in an implicit unstructured hybrid finite volume/element solver for incompressible turbulent flow
Authors: Tu Shuangzhang , Aliabadi Shahrouz , Patel Reena , Watts Marvin
Published: July 2008

In this paper, we describe an implicit hybrid finite volume (FV)/element (FE) incompressible Navier–Stokes solver for turbulent flows based on the Spalart–Allmaras detached eddy simulation (SA‐DES). The hybrid FV/FE solver is based on the segregated pressure correction or projection method. The intermediate velocity field is first obtained by solving the original momentum equations with the matrix‐free implicit cell‐centered FV method. The pressure Poisson equation is solved by the node‐based Galerkin FE method for an auxiliary variable. The auxiliary variable is closely related to the real pressure and is used to update the velocity field and the pressure field. We store the velocity components at cell centers and the auxiliary variable at vertices, making the current solver a staggered‐mesh scheme. The SA‐DES turbulence equation is solved after the velocity and the pressure fields have been updated at the end of each time step. The same matrix‐free FV method as the one used for momentum equations is used to solve the turbulence equation. The turbulence equation provides the eddy viscosity, which is added to the molecular viscosity when solving the momentum equation. In our implementation, we focus on the accuracy, efficiency and robustness of the SA‐DES model in a hybrid flow solver. This paper will address important implementation issues for high‐Reynolds number flows where highly stretched elements are typically used. In addition, some aspects of implementing the SA‐DES model will be described to ensure the robustness of the turbulence model. Several numerical examples including a turbulent flow past a flat plate and a high‐Reynolds number flow around a high angle‐of‐attack NACA0015 airfoil will be presented to demonstrate the accuracy and efficiency of our current implementation. Copyright © 2008 John Wiley & Sons, Ltd.
Mafic plutonic rocks in a continental‐arc setting: geochemistry of 1.87–1.78 Ga rocks from south‐central Sweden and models of their palaeotectonic setting
Authors: Rutanen Henrikki , Andersson Ulf B.
Published: July 2008

Mafic intrusive rocks (1.79–1.78 Ga) of the Transscandinavian Igneous Belt (TIB) and the c. 1.87 Ga Hedesunda Igneous Complex in the Fennoscandian Shield of south‐central Sweden were studied using whole‐rock and isotope geochemistry.

Rock types vary from gabbros/norites (and leucogabbros) to quartz diorites, with Mg# between 76 and 49, and wt% SiO2 between 43.6 and 59.7, indicating some variation in evolutionary levels and variable cumulus components. Geochemical signatures are calc‐alkaline to shoshonitic, large ion lithophile elements and light rare earth elements enriched and high‐field strength elements depleted of continental‐arc type.

εNd(t) ranges between +1.0 and +2.7, and 87Sr/86Sr(t) between 0.7020 and 0.7038. There is no systematic correlation between chemical parameters and isotope ratios. These isotopic data overlap with other mafic plutonic TIB rocks; samples from the Dala Province (DP) tend to overlap with the c. 1.7 Ga basic Dala lavas of TIB at slightly elevated relative Sr/Nd ratios.

With two exceptions, the εNd(t) of +1 to +2 conform to an isotopically ‘mildly depleted’ source, typical for mafic TIB rocks and many Svecofennian rocks in the region. Reported values above εNd(t) +2.0 are scarce in the TIB. Mantle sources represent depleted mantle wedge material that was enriched by fluids/melts not long before (TDM c. 2.0 Ga), that is during subduction in the preceding Svecofennian (2.0–1.87 Ga) and/or during the TIB‐0&1 event (1.85–1.78 Ga). The palaeotectonic settings inferred are active continental margins; N–S‐directed convergence at 1.87 Ga and E–W‐directed at 1.79–1.78 Ga. Copyright © 2008 John Wiley & Sons, Ltd.
Substitute consent for nursing home residents prescribed psychotropic medication
Authors: Rendina Nicola , Brodaty Henry , Draper Brian , Peisah Carmelle , Brugue Esteve
Published: July 2008

Background

Prescribing psychotropic medications for persons with dementia who lack capacity to give informed consent requires proxy consent under NSW Guardianship legislation.

Objective

To survey current practice in complying with legislation and regulations in prescribing psychotropic medications for nursing home residents.

Method

In three Sydney nursing homes, the files of 77 residents identified as having dementia, being on a psychotropic medication and not having capacity to give informed consent, were audited.

Results

In only 6.5% of cases were all regulations adhered to; a further 6.5% attempted and partially completed substitute consent requirements. The problem and the nature of the treatment were documented in 70.1% of cases. In 16.9% of files the only documentation of the prescribed medication was in the medication chart. Doses of medications prescribed were within accepted guidelines.

Conclusion

Current regulations and legislation are not being observed. Recommendations are made as to how to make them more practicable. Copyright © 2008 John Wiley & Sons, Ltd.