bluuebunny/crossref_metadata_2025 huggingface dataset:
Albert Einstein: Revolutionär oder “Bewahrer des Alten”?
Authors: Jung Tobias
Published: July 2008

Albert Einstein: Revolutionary or “Preserver of the Old”? Usually, Albert Einstein and his contributions to the special and general theory of relativity, to cosmology and to quantum physics are considered as “revolutionary”. However, Einstein himself named only one of the papers published in his annus mirabilis 1905 as “very revolutionary”, namely the paper about the light quantum hypothesis. He neither considered his papers about atomic theory nor the papers about the “Electrodynamics of Moving Bodies” as “revolutionary”. In the special and general theory of relativity Einstein did not see the redemption of Newtonian physics but rather its completion. In cosmology which was started off by Einstein's “Cosmological Considerations” in 1917 he adhered to the assumptions of a static and spherically closed universe which originally were introduced by him. His influence on the quantum theory can hardly be overestimated as he was the first to take Planck's light quantum hypothesis as serious physics. Moreover he introduced the concepts of probability and chance into quantum theory. Nonetheless he remained sceptical about quantum physics since he considered it as an incomplete and preliminary description of physical reality. Taking this into consideration one has to state that Einstein saw himself rather as a “preserver of classical physics” than as a revolutionary.
A Macrophage Cell Model for Selective Metalloproteinase Inhibitor Design
Authors: Jacobsen Faith E. , Buczynski Matthew W. , Dennis Edward A. , Cohen Seth M.
Published: July 2008

The desire to inhibit zinc‐dependent matrix metalloproteinases (MMPs) has, over the course of the last 30 years, led to the development of a plethora of MMP inhibitors that bind directly to the active‐site metal. With one exception, all of these drugs have failed in clinical trials, due to many factors, including an apparent lack of specificity for MMPs. To address the question of whether these inhibitors are selective for MMPs in a biological setting, a cell‐based screening method is presented to compare the relative activities of zinc, heme iron, and non‐heme iron enzymes in the presence of these compounds using the RAW264.7 macrophage cell line. We screened nine different zinc‐binding groups (ZBGs), four established MMP inhibitors (MMPis), and two novel MMP inhibitors developed in our laboratory to determine their selectivities against five different metalloenzymes. Using this model, we identified two nitrogen donor compounds—2,2′‐dipyridylamine (DPA) and triazacyclononane (TACN)—as the most selective ZBGs for zinc metalloenzyme inhibitor development. We also demonstrated that the model could predict known nonspecific interactions of some of the most commonly used MMPis, and could also give cross‐reactivity information for newly developed MMPis. This work demonstrates the utility of cell‐based assays in both the design and the screening of novel metalloenzyme inhibitors.
Modeling of Flow Burst, Flow Timing in Lab‐on‐a‐CD Systems and Its Application in Digital Chemical Analysis
Authors: Liu M. , Zhang J. , Liu Y. , Lau W. M. , Yang J.
Published: July 2008

A theoretical model is developed to predict the time‐dependent behaviors of “flow burst” and centrifugal capillary flow in Lab‐on‐a‐CD systems. Enabling the calculation of flow field, flow burst, and flow timing as a function of fluid properties and system specifications, the model is a useful design tool for understanding and controlling flow behaviors in Lab‐on‐a‐CD devices. More importantly, the model shows great promise in the development of a new method for digital chemical analysis.
Classification of GC‐MS measurements of wines by combining data dimension reduction and variable selection techniques
Authors: Ballabio Davide , Skov Thomas , Leardi Riccardo , Bro Rasmus
Published: July 2008

Different classification methods (Partial Least Squares Discriminant Analysis, Extended Canonical Variates Analysis and Linear Discriminant Analysis), in combination with variable selection approaches (Forward Selection and Genetic Algorithms), were compared, evaluating their capabilities in the geographical discrimination of wine samples. Sixty‐two samples were analysed by means of dynamic headspace gas chromatography mass spectrometry (HS‐GC‐MS) and the entire chromatographic profile was considered to build the dataset. Since variable selection techniques pose a risk of overfitting when a large number of variables is used, a method for coupling data dimension reduction and variable selection was proposed. This approach compresses windows of the original data by retaining only significant components of local Principal Component Analysis models. The subsequent variable selection is then performed on these locally derived score variables. The results confirmed that the classification models achieved on the reduced data were better than those obtained on the entire chromatographic profile, with the exception of Extended Canonical Variates Analysis, which gave acceptable models in both cases. Copyright © 2008 John Wiley & Sons, Ltd.
Skew‐normal linear calibration: a Bayesian perspective
Authors: Figueiredo Cléber da Costa , Sandoval Mônica Carneiro , Bolfarine Heleno , Lima Claudia Regina O.P.
Published: July 2008

In this paper, we present a Bayesian approach for estimation in the skew‐normal calibration model, as well as the conditional posterior distributions which are useful for implementing the Gibbs sampler. Data transformation is thus avoided by using the methodology proposed. Model fitting is implemented by proposing the asymmetric deviance information criterion, ADIC, a modification of the ordinary DIC. We also report an application of the model studied by using a real data set, related to the relationship between the resistance and the elasticity of a sample of concrete beams. Copyright © 2008 John Wiley & Sons, Ltd.
A Closer Look: Magnetic Behavior of a Three‐Dimensional Cyanometalate Coordination Polymer Dominated by a Trace Amount of Nanoparticle Impurity
Authors: Lefebvre Julie , Trudel Simon , Hill Ross H. , Leznoff Daniel B.
Published: July 2008

The structure and properties of the K{Ni[Au(CN)2]3} coordination polymer, prepared as a powder at room temperature and recrystallized hydrothermally, are reported. The structure of K{Ni[Au(CN)2]3} contains triply‐interpenetrated Prussian Blue type pseudo‐cubic arrays assembled from the alternation of octahedral NiII centers and [Au(CN)2]− bridging units. SQUID magnetometry studies have shown that K{Ni[Au(CN)2]3} displays typical paramagnetic behavior for isolated NiII centers down to 1.8 K. However, the magnetic behavior of the samples prepared under hydrothermal conditions suggests a superparamagnetic signature superimposed onto a paramagnetic background. After investigating the samples by transmission electron microscopy, it was determined that, in addition to K{Ni[Au(CN)2]3}, the high‐temperature (125, 135, and 165 °C) aqueous reaction of Ni(NO3)2⋅6 H2O with KAu(CN)2 also led to the formation of nanoparticles of NiO and Au as minor side products, and that these dominated the magnetic behavior. Nanoparticles of various sizes and shapes were observed, depending on the reaction conditions. Samples containing nanoparticles were found to be superparamagnetic, exhibiting blocking temperatures of ≈17–22 K, consistent with the behavior expected for NiO nanoparticles. These results illustrate the extreme care that must be taken when examining the physical properties of apparently analytically pure materials prepared by hydrothermal methods.
Reactivity and Antiproliferative Activity of Ferrocenyl–Tamoxifen Adducts with Cyclodextrins against Hormone‐Independent Breast‐Cancer Cell Lines
Authors: Buriez Olivier , Heldt Jan Martin , Labbé Eric , Vessières Anne , Jaouen Gerard , Amatore Christian
Published: July 2008

Hydroxyferrocifen compounds are a new and promising class of ferrocifen‐type breast‐cancer drug candidates. They possess both endocrine‐modulating properties and cytotoxic activity, which come from the tamoxifen skeleton and the presence of a ferrocene moiety, respectively. However, they suffer from reduced solubility in water, which presents a problem for their eventual therapeutic use. Herein, we examined the interactions of hydroxyferrocifen compounds with cyclodextrins (CDs) to evaluate whether or not their electron‐transfer oxidation pathways were affected by their inclusion. It has been demonstrated that these inclusion complexes are soluble in pure water, which shows that CDs can be used to deliver these biologically active molecules. Therefore, a series of these compounds has been investigated by cyclic voltametry in various media in the presence of CDs (β‐CD and Me‐β‐CD). In methanol, the hydroxyferrocifen compounds exhibited a weak interaction with the CD cavity. These interactions became stronger as the amount of added water increased. The complexation effect between the hydroxyferrocifen compounds and β‐CD was found to be stronger if the CD was partially methylated, which is probably due to hydrophobic effects between the cyclopentadienyl ring and/or the aromatic rings and the methoxy groups. Moreover, it appears that the structure of the hydroxyferrocifen compounds affects both their solubility and their complexation dynamics. Investigations in the presence of pyridine show that the base kinetically favors the dissociation of the ferrocifen–CD complex during the electron transfer step, but does not affect the follow‐up reactivity of the electrogenerated ferrocenium cation, which leads eventually to the corresponding quinone methide, as reported in the absence of CD. Accordingly, the cytotoxicity of these β‐CD‐encapsulated organometallic complexes in hormone‐independent breast‐cancer cells (MDA‐MB231) were confirmed to be similar to those obtained in the absence of cyclodextrin.
Optical Properties of Hybrid Dendritic–Mesoporous Titania Nanocomposite Films
Authors: Martínez‐Ferrero Eugenia , Franc Grégory , Mazères Serge , Turrin Cédric‐Olivier , Boissière Cédric , Caminade Anne‐Marie , Majoral Jean‐Pierre , Sanchez Clément
Published: July 2008

New hybrid optical sensors have been prepared by grafting specifically designed fluorescent, functionalised, phosphorus‐containing dendrimers onto a nanocrystalline mesoporous titania thin film formed by evaporation‐induced self‐assembly. The structural characterisation and optical behaviour of these new fluorescent probes have been studied both in solution and after being grafted onto an inorganic network, which resulted in the discovery of improved probing selectivity in the solid state. This new hybrid sensor exhibits high sensitivity to phenolic OH moieties (especially those from resorcinol and 2‐nitroresorcinol), which induce the quenching of fluorescence more efficiently in the solid state than in solution. This effect is a result of the increased spatial proximity of the fluorescent molecules, which is induced by pore confinement that makes the formation of hydrogen bonds between the hydroxyl moieties of the quenchers and the carbonyl groups of the dendrimer easier.
A Mesoporous 3D Hybrid Material with Dual Functionality for Hg2+ Detection and Adsorption
Authors: Ros‐Lis José V. , Casasús Rosa , Comes María , Coll Carmen , Marcos M. Dolores , Martínez‐Máñez Ramón , Sancenón Félix , Soto Juan , Amorós Pedro , Haskouri Jamal El , Garró Nuria , Rurack Knut
Published: July 2008

Dual‐function hybrid material U 1 was designed for simultaneous chromofluorogenic detection and removal of Hg2+ in an aqueous environment. Mesoporous material UVM‐7 (MCM41 type) with homogeneously distributed pores of about 2–3 nm in size, a large specific surface area exceeding 1000 m2 g−1, and nanoscale particles was used as an inorganic support. The mesoporous solid is decorated with thiol groups that were treated with squaraine dye III to give a 2,4‐bis(4‐dialkylaminophenyl)‐3‐hydroxy‐4‐alkylsulfanylcyclobut‐2‐enone (APC) derivative that is covalently anchored to the inorganic silica matrix. The solid was characterised by various techniques including X‐ray diffraction, transmission electron microscopy, Raman spectroscopy, and nitrogen adsorption. This hybrid solid is the chemodosimeter for Hg2+ detection. Hg2+ reacts with the APC fragment in U 1 with release of the squaraine dye into the solution, which turns deep blue and fluoresces strongly. Naked‐eye Hg2+ detection is thus accomplished in an easy‐to‐use procedure. In contrast, U 1 remains silent in the presence of other thiophilic transition metal ions, alkali and alkaline earth metal ions, or anions ubiquitously present in water such as chloride, carbonate, sulfate, and phosphate. Material U 1 acts not only as chemodosimeter that signals the presence of Hg2+ down to parts‐per‐billion concentrations, but at the same time is also an excellent adsorbent for the removal of mercury cations from aqueous solutions. The amount of adsorbed mercury ranges from 0.7 to 1.7 mmol g−1, depending on the degree of functionalisation. In addition, hybrid material U 1 can be regenerated for both sensing and removal purposes. As far as we know, U 1 is the first example of a promising new class of polyfunctional hybrid supports that can be used as both remediation and alarm systems by selective signalling and removal of target species of environmental importance. Model compounds based on silica gel (G 1), fumed silica (F 1), and micrometre‐sized MCM‐41 scaffolds (M 1) were also prepared and studied for comparative purposes.
Organometallic–Polypeptide Block Copolymers: Synthesis and Self‐Assembly of Poly(ferrocenyldimethylsilane)‐b‐Poly(ε‐benzyloxycarbonyl‐L‐Lysine)
Authors: Wang Yishan , Zou Shan , Kim Kyoung Taek , Manners Ian , Winnik Mitchell A.
Published: July 2008

A new type of metallopolymer‐polypeptide block copolymer poly(ferrocenyldimethylsilane)‐b‐poly (ε‐benzyloxycarbonyl‐l‐lysine) was synthesized by ring‐opening polymerization of ε‐benzyloxycarbonyl‐l‐lysine N‐carboxyanhydride initiated by using a primary amino‐terminated poly(ferrocenyldimethylsilane). Studies on the self‐organization behavior of this polypeptide block copolymer in both the bulk state and in solution were performed. In the bulk state, a cylindrical‐in‐lamellar structure was observed in a compositionally asymmetric sample. Rod‐like micelles with a polyferrocenylsilane core formed in a polypeptide‐selective solvent alone or in the presence of a common solvent. Significantly, an additional small quantity of the common solvent assisted the formation of longer micelles and micelles with better shape‐regularity. This is attributed to a decrease in the number of nucleation events and PFS core reorganization effects.
Polyviologen Dendrimers as Hosts and Charge‐Storing Devices
Authors: Ronconi Célia M. , Stoddart J. Fraser , Balzani Vincenzo , Baroncini Massimo , Ceroni Paola , Giansante Carlo , Venturi Margherita
Published: July 2008

Two dendrimers were designed and synthesized that contain a 1,3,5‐trisubstituted benzenoid core and incorporate 9 and 21 viologen (4,4′‐bipyridinium) units in their branches in addition to hydrophilic (aryloxy) terminal groups. For comparison purposes, model compounds containing one and two viologen units were also studied. These polycationic dendrimers form strong host–guest complexes with the dianionic form of the red dye eosin in dilute CH2Cl2 solutions. Titration experiments, based on fluorescence measurements, showed that each viologen unit in the dendritic structures becomes associated with an eosin dianion. Electrochemical (in MeCN) and photosensitization (in CH2Cl2) experiments revealed that only a fraction of the viologen units present in the dendritic structures can be reduced. This fraction corresponds to the number of viologen units present in the outer shells of the dendrimers. The reasons for incomplete charge pooling are discussed. Comparison with the behavior of polyviologen dendrimers that are terminated with bulky tetraarylmethane groups and were studied previously enabled the role played by the terminal groups in the redox and hosting properties to be elucidated.
Two‐Dimensionally Extended Porphyrin Tapes: Synthesis and Shape‐Dependent Two‐Photon Absorption Properties
Authors: Nakamura Yasuyuki , Jang So Young , Tanaka Takayuki , Aratani Naoki , Lim Jong Min , Kim Kil Suk , Kim Dongho , Osuka Atsuhiro
Published: July 2008

We report the synthesis and characterization of L‐ and T‐shaped porphyrin tapes as extensible structural motifs of two‐dimensionally extended porphyrin tapes. The two‐photon absorption (TPA) cross‐section values (σ(2)) for L‐ and T‐shaped porphyrin tapes as well as those for linear trimeric and tetrameric porphyrin tapes were measured by an open‐aperture Z‐scan method at 2300 nm, a wavelength at which the one‐photon absorption contribution is either zero or almost negligible. Under these conditions, the σ(2) values for the linear porphyrin tape trimer and tetramer were determined to be 18 500 and 41 200 GM, respectively. The σ(2) value for the L‐shaped trimer was determined to be 8700 GM, which is only half that of the linear trimer, whereas the σ(2) value for the T‐shaped tetramer was measured to be 35 700 GM. These results clearly indicate the dependence of the TPA cross‐section on the molecular shape, which underscores the importance of directionality in the π‐conjugation pathway for the enhancement of TPA cross‐ section.
A Flexible Method for the Conjugation of Aminooxy Ligands to Preformed Complexes of Nucleic Acids and Lipids
Authors: Hecker James G. , Berger Gideon O. , Scarfo Keith A. , Zou Shaomin , Nantz Michael H.
Published: July 2008

Attachment of targeted ligands to nonviral DNA or RNA delivery systems is a promising strategy that seeks to overcome the poor target selectivity generally observed in systemic delivery applications. Several methods have been developed for the conjugation of ligands to lipids or polymers, however, direct conjugation of ligands onto lipid– or polymer–nucleic acid complexes is not as straightforward. Here, we examine an oximation approach to directly label a lipoplex formulation. Specifically, we report the synthesis of a cationic diketo lipid DMDK, and its use as a convenient ligation tool for attachment of aminooxy‐functionalized reagents after its complexation with DNA. We demonstrate the feasibility of direct lipoplex labeling by attaching an aminooxy‐functionalized fluorescent probe onto pre‐formed plasmid DNA–DMDK lipoplexes (luciferase, GFP). The results reveal that DMDK protects DNA from degradation on exposure to either DNase or human cerebral spinal fluid, and that simple mixing of DMDK lipoplexes with the aminooxy probe labels the complexes without sacrificing transfection efficiency. The biocompatibility and selectivity of this method, as well as the ease of bioconjugation, make this labeling approach ideal for biological applications.
Syntaxin 3b is a t‐SNARE specific for ribbon synapses of the retina
Authors: Curtis Leigh B. , Doneske Blair , Liu Xiaoqin , Thaller Christina , McNew James A. , Janz Roger
Published: August 2008

Previous studies have demonstrated that ribbon synapses in the retina do not contain the t‐SNARE (target‐soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor) syntaxin 1A that is found in conventional synapses of the nervous system. In contrast, ribbon synapses of the retina contain the related isoform syntaxin 3. In addition to its localization in ribbon synapses, syntaxin 3 is also found in nonneuronal cells, where it has been implicated in the trafficking of transport vesicles to the apical plasma membrane of polarized cells. The syntaxin 3 gene codes for four different splice forms, syntaxins 3A, 3B, 3C, and 3D. We demonstrate here by using analysis of EST databases, RT‐PCR, in situ hybridization, and Northern blot analysis that cells in the mouse retina express only syntaxin 3B. In contrast, nonneuronal tissues, such as kidney, express only syntaxin 3A. The two major syntaxin isoforms (3A and 3B) have an identical N‐terminal domain but differ in the C‐terminal half of the SNARE domain and the C‐terminal transmembrane domain. These two domains are thought to be directly involved in synaptic vesicle fusion. The interaction of syntaxin 1A and syntaxin 3B with other synaptic proteins was examined. We found that both proteins bind Munc18/N‐sec1 with similar affinity. In contrast, syntaxin 3B had a much lower binding affinity for the t‐SNARE SNAP25 compared with syntaxin 1A. By using an in vitro fusion assay, we could demonstrate that vesicles containing syntaxin 3B and SNAP25 could fuse with vesicles containing synaptobrevin2/VAMP2, demonstrating that syntaxin 3B can function as a t‐SNARE. J. Comp. Neurol. 510:550–559, 2008. © 2008 Wiley‐Liss, Inc.
Photothermal Detection of Individual Gold Nanoparticles: Perspectives for High‐Throughput Screening
Authors: Kulzer Florian , Laurens Niels , Besser Jaya , Schmidt Thomas , Orrit Michel , Spaink Herman P.
Published: July 2008

We use photothermal microscopy to detect and image individual gold nanoparticles that are either embedded in a polymer film or immobilized in an aqueous environment. Reducing the numerical aperture of the detection optics allows us to achieve a 200‐fold‐enlarged detection volume while still retaining sufficient detectivity. We characterize the capabilities of this approach for the detection of gold colloids with a diameter of 20 nm, with emphasis on practical aspects that are important for high‐throughput‐screening applications. The extended detection volume in combination with the stability of the photothermal signal are major advantages compared to fluorescence‐based approaches, which are limited by photoblinking and photobleaching. Careful consideration is given to the trade‐off between the maximum increase in local temperature that can be tolerated by a biological specimen and the minimum integration time needed to reliably determine whether a given volume contains a target species. We find that our approach has the potential to increase the detection‐limited flow rate (i.e. the limit given by the detection volume divided by the minimum detection time) by two to three orders of magnitude.
Adsorption of 1,3‐Benzenedithiol and 1,3‐Benzenedimethanethiol on Gold Surfaces
Authors: Lim Jong Kuk , Kim Youngmin , Kwon Ohyun , Joo Sang‐Woo
Published: July 2008

The adsorption characteristics of 1,3‐benzenedithiol (1,3‐BDT) and 1,3‐benzenedimethanethiol (1,3‐BDMT) on Au surfaces are investigated by means of surface‐enhanced Raman scattering, UV/Vis absorption spectroscopy, and cyclic voltammetry (CV). 1,3‐BDMT is found to adsorb via two S–Au linkages at concentrations below monolayer coverage, but to have an upright geometry as the concentration increases on Au nanoparticles. On the other hand, 1,3‐BDT is found to adsorb by forming two S–Au linkages, regardless of concentration, based on the disappearance of the ν(SH)free stretching band. Because of the absence of the methylene unit, 1,3‐BDT appeares not to self‐assemble efficiently on Au surfaces. The UV/Vis absorption spectroscopy and CV techniques are also applied to check the formation of self‐assembled monolayers of 1,3‐BDT and 1,3‐BDMT on Au. Density functional theory calculations based on a simple adsorption model using an Au8 cluster are performed to better understand the nature of the adsorption characteristics of 1,3‐BDT and 1,3‐BDMT on Au surfaces.
Associative Versus Dissociative Mechanisms of Phosphate Monoester Hydrolysis: On the Interpretation of Activation Entropies
Authors: Kamerlin Shina C. L. , Florián Jan , Warshel Arieh
Published: July 2008

Phosphate monoester and anhydride hydrolysis is ubiquitous in biology, being involved in, amongst other things, signal transduction, energy production, and the regulation of protein function. Therefore, this reaction has understandably been the focus of intensive research. Nevertheless, the precise mechanism by which phosphate monoester hydrolysis proceeds remains controversial. Traditionally, it has been assumed and frequently implied that a near‐zero activation entropy is indicative of a dissociative pathway. Herein, we examine free‐energy surfaces for the hydrolysis of the methyl phosphate dianion and the methyl pyrophosphate trianion in aqueous solution. In both cases, the reaction can proceed through either compact or expansive concerted (ANDN) transition states, with fairly similar barriers. We have evaluated the activation entropies for each transition state and demonstrate that both associative and dissociative transition states have near‐zero entropies of activation that are in good agreement with experimental values. Therefore, we believe that the activation entropy alone is not a useful diagnostic tool, as it depends not only on bond orders at the transition state, but also on other issues that include (but are not limited to) steric factors determining the configurational volumes available to reactants during the reaction, solvation and desolvation effects that may be associated with charge redistribution upon approaching the transition state and entropy changes associated with intramolecular degrees of freedom as the transition state is approached.
Significance of intercellular spaces (windows) in effusion fluid cytology: A study of 46 samples
Authors: Murugan Paari , Siddaraju Neelaiah , Habeebullah Syed , Basu Debdatta
Published: August 2008

The presence and nature of intercellular windows were studied on 46 body cavity fluid samples chosen on the basis of an unequivocal diagnosis on May‐Grünwald‐Giemsa (MGG)/Papanicolaou‐stained smears and cell blocks. Of these, 24 cases had adenocarcinoma (AC) and seven had reactive mesothelium (RM) with 15 having distinct populations of both. Mucicarmine and PAS stains were used wherever indicated. The specificity of windows for predicting reactive mesothelium was evaluated. Intercellular windows were found in all cases of reactive mesothelium coinciding with the presence of the fuzzy peripheral microvillous borders. Surprisingly, as many as 17/39 (44%) of the adenocarcinomas also exhibited this feature, of which 13 had a distinctly visible evenly distributed ciliated cell membrane. In addition, 30/39 (77%) cases of AC exhibited a “window‐like” appearance caused by cytoplasmic vacuolation. None of the adenocarcinoma clusters with true window formation showed positivity for the mucin stains, whereas all the clusters with pseudowindows caused by vacuolation were stained. Thus the specificity of intercellular windows for RM was merely 56%, though the sensitivity was 100%. On the other hand, the absence of windows was 100% specific for adenocarcinoma. Intercellular windows, though a feature of reactive mesothelial cell populations, can also be found in cases of ciliated adenocarcinomas and may not have a significant predictive value. Diagn. Cytopathol. 2008;36:628–632. © 2008 Wiley‐Liss, Inc.
Potential use of insulin as an anti‐inflammatory drug
Authors: Dandona Paresh , Chaudhuri Ajay , Ghanim Husam , Mohanty Priya
Published: July 2008

Acute hyperglycemia worsens morbidity and mortality in critically ill patients. The control of hyperglycemia with insulin improves clinical outcomes in patients with a stay of more than 3–5 days in the intensive care unit (ICU) and in coronary artery bypass graft (CABG) patients. However, clinical benefits of insulin infusion have not been seen consistently in patients with acute coronary syndromes. Since all previous studies in the ICU have centered on the normalization of glycemia, we still do not know whether insulin exerts beneficial effects over and above those observed with reduction of blood glucose concentrations. The regimens used in acute coronary syndromes infuse fixed doses of insulin with high rates of glucose and are usually associated with hyperglycemia; this may neutralize the beneficial effects of insulin. In this article, we discuss data demonstrating an anti‐inflammatory effect of insulin and a pro‐inflammatory effect of glucose. We provide a mechanistic justification for the benefits of maintaining euglycemia with insulin infusions in the hospitalized patients. To investigate the clinical benefits of the anti‐inflammatory effects of insulin, we also suggest further investigations directed toward optimization of insulin infusion regimens to determine whether restoration of glucose levels toward normal with higher infusion rates and concentrations of insulin will lead to further improvement in outcomes in the critical care and acute coronary syndromes. Drug Dev Res 69:101–110, 2008 © 2008 Wiley‐Liss, Inc.
Insulin treatment in pregnancy
Authors: Trujillo Angelina
Published: July 2008

Due to the teratogenic potential of many oral hypoglycemic agents, insulin injections are the primary treatment for diabetes in pregnant women. There has been insufficient study of insulin glargine in pregnancy. Therefore, NPH insulin continues to be the primary basal insulin used in pregnancies. The insulin requirement rises substantially in the second and third trimesters. NPH insulin and rapid‐acting insulin are mixed typically in a 1:1 ratio and administered at each main meal. The insulin pump is a viable alternative to multiple injections. During labor, insulin requirements decrease sharply, and in the post‐partum period return to the levels of the non‐pregnant state. Drug Dev Res 69:119–123, 2008.© 2008 Wiley‐Liss, Inc.
The science behind Exubera®
Authors: Schachner Holly
Published: July 2008

Fear of needles constitutes a significant barrier to the use of insulin. Lung tissue offers a large permeable surface for rapid and predictable absorption of insulin into the bloodstream. Exubera insulin was the first inhaled insulin to be approved and marketed for clinical use. The present review is intended to summarize the data to present with Exubera insulin. The pharmacodynamic effect of this inhaled insulin is similar to that of injected regular human insulin. There are small changes in lung function that parallel age‐related changes in patients who are not taking inhaled insulin. Cough occurs frequently but does not affect the overall insulin effect. Patients who start using insulin gain weight, but there is less weight gain with Exubera use than with comparable doses of injected insulin. In multiple studies, the incidence of hypoglycemia with Exubera is similar to that with regular insulin. There is concern that insulin may act as a growth factor on the lung epithelium. Recently, analysis of existing data showed that six patients on Exubera developed lung cancer compared to only one on comparator injectable insulin, all cases occurred in former smokers. However, studies were not powered for this safety issue and numbers were too small to conclude a causal relationship between Exubera exposure and occurrence of lung cancer. Pfizer decided to discontinue marketing Exubera on October 18, 2007. The decision was based upon failure to meet financial landmarks rather than due to concern about possible safety issues. Drug Dev Res 69:130–137, 2008. © 2008 Wiley‐Liss, Inc.
Preserving β Cells in Type 1 Diabetes mellitus: the role of immunological tolerance
Authors: Pillemer Stanley R.
Published: July 2008

Type 1 diabetes mellitus (T1DM) is characterized by an autoimmune attack on beta cells of the islets of Langerhans. This immunological attack is mediated by effector T‐lymphocytes and results in the destruction of the β cells. One approach to abrogating the immunological attack is to use immunosuppressive treatments. Such treatments tend to broadly suppress the immune system. A better approach is to develop treatments that induce tolerance. Autoimmune diseases are associated with the presence of inadequate numbers of functionally active regulatory T cells (Tregs). Tregs can induce a state of immunological tolerance and suppress the inflammation and destruction of target tissues. Teplizumab, also known as hOKT3γ1 (Ala‐Ala), is a humanized monoclonal antibody that induces Tregs. In clinical trials, treatment with this antibody preserved insulin production and improved metabolic control during the first year of T1DM. A pivotal multinational trial is in progress to determine the efficacy and safety of teplizumab in the treatment of new onset T1DM. Drug Dev Res 69:153–157, 2008. ©2008 Wiley‐Liss, Inc.
Vanadium(I) Chloride and Lithium Vanadium(I) Dihydride as Selective Epimetallating Reagents for π‐ and σ‐Bonded Organic Substrates
Authors: Eisch John J. , Fregene Paul O.
Published: July 2008

Subvalent vanadium(I) salts, of empirical formulas, VCl, vanadium(I) chloride and LiVH2, lithium vanadium(I) dihydride, whose efficient preparation, structural constitution and mode of reaction toward certain organic substrates have been described in a preceding article, are here evaluated in their reactions toward a wide variety of π‐ and σ‐bonded organic substrates, namely carbonyl, imine, azo, alkene, 1,3‐diene, nitrile π‐bonds and C–X, C–O, C–N and N–N σ‐bonds. Compared with the high reactivity of CrCl and LiCrH2 reagents in attacking both types of bonds, the VCl and LiVH2 reagents were much milder and selective in epimetallating π‐bonds, often forming the 1:1 adduct of LiVH2 and π‐bonded substrate as the major product. Finally, the vanadium reagents showed little tendency to cleave C–O, C–S and C–N bonds and a smaller scope in cleaving C–X bonds than their chromium counterparts. Because of their selectivity these vanadium reagents offer the following preparative promise: 1) smooth McMurry carbonyl coupling to their reductive dimers; 2) deoxygenation of epoxides; 3) selective aromatic C–X reduction; 4) high yields of epimetallated carbonyls or imines as intermediates to ‐hydroxy and ‐amino acids; 5) 1,4‐reductions of 1,3‐alkadienes; 6) reductive dimerization of nitriles to ketones; 7) 1,4 or 1,n‐epimetallations leading to acyloins or indoles; and 8) reductive dimerizations of azines to produce unusual imidazole derivatives. In explaining the greater kinetic stability of the 1:1 LiVH2 adduct with carbonyl or imine substrates it is pointed out that such epimetallated adducts from LiVH2 would likely be diamagnetic, whereas such adducts from LiCrH2 have an unpaired electron on the Cr center and hence would rupture, so that the electron would be on the C center.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
Correlations between pyrolysis combustion flow calorimetry and conventional flammability tests with halogen‐free flame retardant polyolefin compounds
Authors: Cogen Jeffrey M. , Lin Thomas S. , Lyon Richard E.
Published: July 2008

Seven halogen‐free flame retardant (FR) compounds were evaluated using pyrolysis combustion flow calorimetry (PCFC) and cone calorimetry. Performance of wires coated with the compounds was evaluated using industry standard flame tests. The results suggest that time to peak heat release rate (PHRR) and total heat released (THR) in cone calorimetry (and THR and temperature at PHRR in PCFC) be given more attention in FR compound evaluation. Results were analyzed using flame spread theory. As predicted, the lateral flame spread velocity was independent of PHRR and heat release capacity. However, no angular dependence of flame spread velocity was observed. Thus, the thermal theory of ignition and flame spread, which assumes that ignition at the flame front occurs at a particular flame and ignition temperature, provides little insight into the performance of the compounds. However, results are consistent with a heat release rate greater than about 66kW/m2 during flame propagation for sustained ignition of insulated wires containing mineral fillers, in agreement with a critical heat release rate criterion for burning. Mineral fillers can reduce heat release rate below the threshold value by lowering the flaming combustion efficiency and fuel content. A rapid screening procedure using PCFC is suggested by logistic regression of the binary (burn/no‐burn) results. Copyright © 2008 John Wiley & Sons, Ltd.
A computational study of gas flow in a De‐Laval micronozzle at different throat diameters
Authors: Lin C. X. , Gadepalli V. V. V.
Published: July 2008

A numerical study has been carried out to investigate the gas flows in a micronozzle using a continuum model under both slip and no‐slip boundary conditions. The governing equations were solved with a finite volume method. The numerical model was validated with available experimental data. Numerical results of exit thrust showed good agreement with experimental data except at very low Reynolds numbers. For parametric studies on the effect of geometric scaling, the nozzle throat diameter was varied from 10 to 0.1 mm, whereas throat Reynolds number was varied from 5 to 2000. A correlation has also been developed to calculate the specific impulse at specified throat diameter and Reynolds number. The effect of different gases on the specific impulse of the nozzle, such as helium, nitrogen, argon and carbon dioxide, was also examined. Copyright © 2008 John Wiley & Sons, Ltd.
Evaluation of GdBaCo2O5 + δ as Cathode Material for Doped Lanthanum Gallate Electrolyte IT‐SOFCs
Authors: Peña‐Martínez J. , Tarancón A. , Marrero‐López D. , Ruiz‐Morales J. C. , Núñez and P.
Published: July 2008

The layered perovskite GdBaCo2O5 + δ (GBCO), recently proposed for intermediate temperature solid oxide fuel cell applications, was investigated and compared with Ba0.5Sr0.5Co0.8Fe0.2O3 – δ (BSCF) cathode material using La0.9A0.1Ga0.8Mg0.2O2.85 (A=Sr,Ba) as electrolytes. Area‐specific resistance was measured by impendance spectroscopy in symmetrical cells. The cobaltites were prepared by a modified citrate sol–gel route and tested as cathode materials for doped lanthanum gallate‐based cells using dry H2 as fuel and air as oxidant, rendering power density values of 180 and 240 mW cm–2 at 1,073 K (1 mm thick pellets) for GBCO and BSCF fuel cells, respectively.
What makes responses prepotent for young children? Insights from the grass–snow task
Authors: Simpson Andrew , Riggs Kevin J.
Published: July 2008

Understanding how responses become prepotent is essential for understanding when inhibitory control is needed in everyday behaviour. We investigated prepotency in the grass–snow task—in which a child points to a green card when the experimenter says ‘snow’ and a white card when the experimenter says ‘grass’. Experiment 1 (n=48, mean age=3.5 years) investigated the response method effect—whether pointing is prepotent because it is habitual. Experiment 2 (n=60, mean age=3.5 years) investigated the response set effect—whether responses are prepotent because the child plans to make them in the task. Experiment 2 also provided evidence that children could remember the rules in the task. Experiment 3 (n=30, mean age=3.4 years) produced further evidence that children could remember these rules. We found no evidence for the response method and response set effects, suggesting that prepotency in the grass–snow task is more ‘stimulus‐driven’ than in tasks previously studied. The implications of our findings are discussed in relation to other developmental inhibitory tasks and to children's reliance on inhibitory control to regulate their everyday behaviour. Copyright © 2008 John Wiley & Sons, Ltd.
Maidum's challenge, legal and governance issues in dealing with cross‐border business enterprise group insolvencies
Authors: Sarra Janis
Published: July 2008

Maidum was an early Egyptian pyramid, the first attempt to build a true pyramid; but it suffered a spectacular collapse. In many jurisdictions, corporate structures are pyramidal in shape, with related enterprises conducting business in multiple jurisdictions. Where such structures financially collapse, creditors of different entities within a business enterprise group compete for limited assets that may or may not be located in the entity in which they have advanced credit and thus have claims. This article discusses the challenges posed by cross‐border business enterprise group insolvency and the range of procedural mechanisms that may be available to protect creditors' claims, articulating broad principles that should be considered in such cases. The choice of cooperation and coordination mechanism is driven in part by whether the particular jurisdiction emphasizes liquidation or restructuring as the objective of the insolvency proceeding. Copyright © 2008 John Wiley & Sons, Ltd.
Comparing empirical results of transaction avoidance rules studies
Authors: van Dijck Gijs
Published: July 2008

Empirical legal research in the United Kingdom (UK) and in The Netherlands (NL) has provided data on the extent to which the transaction avoidance rules (avoidance powers, actio Pauliana) generate practical problems. This paper's goal is to explore the similarities and differences of the data. To achieve this, existing empirical data found in Dutch and UK research are compared. From the comparison, it follows that the UK and NL share similar problems, that is there are no proceeds in a substantial number of cases in which the office‐holder (or liquidator) encounters a suspect transaction, the majority of the disputes are conducted in the shadow of the law, proceeds are obtained more often from settlements than from proceedings, insufficient funds and evidence problems are experienced as major obstacles for successfully invoking the transaction avoidance rules, and a presumption or shift of burden of proof influences the outcome significantly. Copyright © 2008 John Wiley & Sons, Ltd.
Requirement of a functional spindle checkpoint for arsenite‐induced apoptosis
Authors: Wu Yi‐Chen , Yen Wen‐Yen , Yih Ling‐Huei
Published: July 2008

To understand the potential influence of spindle checkpoint function in response to arsenic trioxide (ATO)‐induced apoptosis observed in cancer cell lines, we examined the correlation between activation of the spindle checkpoint and susceptibility to ATO‐induced apoptosis in 10 cancer cell lines lacking functional p53. The ability to functionally activate the spindle checkpoint in each cancer cell line was assessed by the induction of mitotic arrest after Taxol treatment. Bromodeoxyuridine (BrdU) pulse‐chase analysis of Taxol‐treated cell lines with low mitotic arrest showed that they were not arrested at mitosis but divided abnormally, confirming that spindle checkpoint activation was impaired in these cell lines. Our results demonstrate that apoptosis was significantly induced by ATO in cancer cell lines with functional activation of the spindle checkpoint and substantial induction of mitotic arrest. Cell lines with negligible mitotic arrest exhibited little ATO‐induced apoptosis. However, no such correlation was observed following treatment of cells with camptothecin, a topoisomerase I inhibitor. Furthermore, attenuation of the spindle checkpoint function by small interfering RNA‐mediated silencing of BubR1 and Mad2 in cancer cells that were susceptible to ATO‐induced mitotic arrest and apoptosis greatly reduced the induction of mitotic arrest and apoptosis by ATO and increased the formation of micronuclei or multinuclei in survived cells. The marked correlation between ATO‐induced mitotic arrest and apoptosis indicates that the induction of apoptosis by ATO was highly dependent on the functional activation of the spindle checkpoint in cancer cells lacking normal p53 function. J. Cell. Biochem. 105: 678–687, 2008. © 2008 Wiley‐Liss, Inc.
PK 11195 differentially affects cell survival in human wild‐type and 18 kDa translocator protein‐silenced ADF astrocytoma cells
Authors: Chelli Beatrice , Salvetti Alessandra , Da Pozzo Eleonora , Rechichi Mariarosa , Spinetti Francesca , Rossi Leonardo , Costa Barbara , Lena Annalisa , Rainaldi Giuseppe , Scatena Fabrizio , Vanacore Renato , Gremigni Vittorio , Martini Claudia
Published: July 2008

Gliomas are the most common brain tumours with a poor prognosis due to their aggressiveness and propensity for recurrence. The 18 kDa translocator protein (TSPO) has been demonstrated to be greatly expressed in glioma cells and its over‐expression has been correlated with glioma malignance grades. Due to both its high density in tumours and the pro‐apoptotic activity of its ligands, TSPO has been suggested as a promising target in gliomas. With the aim to evidence if the TSPO expression level alters glioma cell susceptibility to undergo to cell death, we analysed the effects of the specific TSPO ligand, PK 11195, in human astrocytoma wild‐type and TSPO‐silenced cell lines. As first step, TSPO was characterised in human astrocytoma cell line (ADF). Our data demonstrated the presence of a single class of TSPO binding sites highly expressed in mitochondria. PK 11195 cell treatment activated an autophagic pathway followed by apoptosis mediated by the modulation of the mitochondrial permeability transition. In TSPO‐silenced cells, produced by siRNA technique, a reduced cell proliferation rate and a decreased cell susceptibility to the PK 11195‐induced anti‐proliferative effect and mitochondrial potential dissipation were demonstrated respect to control cells. In conclusion, for the first time, PK 11195 was demonstrated to differentially affect glioma cell survival in relation to TSPO expression levels. These results encourage the development of specific‐cell strategies for the treatment of gliomas, in which TSPO is highly expressed respect to normal cells. J. Cell. Biochem. 105: 712–723, 2008. © 2008 Wiley‐Liss, Inc.
From fibroblasts to iPS cells: Induced pluripotency by defined factors
Authors: Zhao Rui , Daley George Q.
Published: July 2008

Patient‐specific pluripotent cells may serve as a limitless source of transplantable tissue to treat a number of human blood and degenerative diseases without causing immune rejection. Recently, isolation of patient‐specific induced pluripotent stem (iPS) cells was achieved by transducing fibroblasts with four transcription factors, Oct4, Sox2, Klf4, and c‐Myc. However, the use of oncogenes and retrovirus in the current iPS cell establishment protocol raises safety concerns. To generate clinical quality iPS cells, the development of novel reprogramming methods that avoid permanent genetic modification is highly desired. The molecular mechanisms that mediate reprogramming are essentially unknown. We argue that establishment of a stable and self‐sustainable ES‐specific transcriptional regulatory network is essential for reprogramming. Such a system should include expression of Oct4, Sox2, Nanog and probably other pluripotenty‐promoting factors from endogenous loci and establishment of a permissive epigenetic state to maintain such expression. In addition, though not yet proven experimentally, overcoming cellular senescence of fibroblasts by inactivating Rb and p53 pathways and up‐regulating telomerase activity may also be required. J. Cell. Biochem. 105: 949–955, 2008. © 2008 Wiley‐Liss, Inc.
Is regulation of aromatase expression in reptiles the key to understanding temperature‐dependent sex determination?
Authors: Lance Valentine A.
Published: July 2008

A brief review of our current understanding (or lack of understanding) of the molecular basis of temperature‐dependent sex determination (TSD) in reptiles is presented. Current theories are discussed: yolk steroids as sex determinants, the brain as the driver for TSD and the enzyme aromatase and estrogen production as the possible determinants of sex. There is little evidence to support the first two theories, but enough evidence to keep the third theory in play. As yet, however, we have no molecular understanding of how a two‐degree difference in temperature during the temperature‐sensitive phase of egg incubation can initiate the molecular cascade that determines whether the indifferent gonad develops as an ovary or a testis. J. Exp. Zool. 311A:314–322, 2009. © 2008 Wiley‐Liss, Inc.