bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of human kallikreins 5 and 7 by the serine protease inhibitor lympho-epithelial Kazal-type inhibitor (LEKTI)
Authors: Schechter Norman M. , Choi Eun-Jung , Wang Zhe-Mei , Hanakawa Yasushi , Stanley John R. , Kang Ya'an , Clayman Gary L. , Jayakumar Arumugam
Published: November 2005

LEKTI is a 120-kDa protein that plays an important role in skin development, as mutations affecting LEKTI synthesis underlie Netherton syndrome, an inherited skin disorder producing severe scaling. Its primary sequence indicates that the protein consists of 15 domains, all resembling a Kazal-type serine protease inhibitor. LEKTI and two serine proteases belonging to the human tissue kallikrein (hK) family (hK5 and hK7) are expressed in the granular layer of skin. In this study, we characterize the interaction of two recombinant LEKTI fragments containing three or four intact Kazal domains (domains 6–8 and 9–12) with recombinant rhK5, a trypsin-like protease, and recombinant rhK7, a chymotrypsin-like protease. Both fragments inhibited rhK5 similarly in binding and kinetic studies performed at pH 8.0, as well as pH 5.0, the pH of the stratum corneum where both LEKTI and proteases may function. Inhibition equilibrium constants (Ki) measured either directly in concentration-dependent studies or calculated from measured association (kass) and dissociation (kdis) rate constants were 1.2–5.5 nM at pH 8.0 and 10–20 nM at pH 5.0. At pH 8.0,kassandkdisvalues were 4.7×105 M−1s−1and 5.5×10−4 s−1, and at pH 5.0 they were 4.0×104 M−1 s−1and 4.3×10−4 s−1, respectively. The lowKiandkdisvalues (t1/2of 20–25 min) indicate tight and specific association. Only fragment 6–9′ was a good inhibitor of rhK7, demonstrating aKiof 11 nM at pH 8.0 in a reaction that was rapidly reversible. These results show that LEKTI, at least in fragment form, is a potent inhibitor of rhK5 and that this protease may be a target of LEKTI in human skin.
Truncated Stop Loss as Optimal Reinsurance Agreement in One-period Models
Authors: Kaluszka Marek
Published: November 2005

We consider several one-period reinsurance models and derive a rule which minimizes the ruin probability of the cedent for a fixed reinsurance risk premium. The premium is calculated according to the economic principle, generalized zero-utility principle, Esscher principle or mean-variance principles. It turns out that a truncated stop loss is an optimal treaty in the class ofallreinsurance contracts. The result is also valid for models not involving ruin probability. An example is the Arrow model with the Kahneman-Tversky value function.
Pareto-optimal Contracts in an Insurance Market
Authors: Golubin A.Y.
Published: November 2005

In distinction to the Borch’s model of a reinsurance market, this paper treats the problem of optimal risk exchange in an insurance market where treaties are allowed between the insurer and each insured only, not among insureds themselves. A characterization of the Pareto-optimal contract is found. It is shown that the indemnity function in the contract is of a coinsurance kind. We also present a way of finding Pareto-optimal contracts under individual rationality constraints. The obtained results are compared with those of the known model of risk exchange in a reinsurance market.
Multivariate Counting Processes: Copulas and Beyond
Authors: Bäuerle Nicole , Grübel Rudolf
Published: November 2005

Multivariate stochastic processes with Poisson marginals are of interest in insurance and finance; they can be used to model the joint behaviour of several claim arrival processes, for example. We discuss various methods for the construction of such models, with particular emphasis on the use of copulas. An important class of multivariate counting processes with Poisson marginals arises if the events of a background Poisson process with constant intensity are moved forward in time by a random amount and possibly deleted; here we think of the events of the background process as triggering later claims in different categories. We discuss structural aspects of these models, their dependence properties together with stochastic order aspects, and also some related computational issues. Various actuarial applications are indicated.
Applying the Proportional Hazard Premium Calculation Principle
Authors: Maria de Lourdes Centeno , João Andrade e Silva
Published: November 2005

In this paper we discuss the application of the proportional hazard premium calculation principle.

In Section 2 we propose a method to calculate the proportional hazard premium of a compound risk when the severity distribution is subexponential.

In Section 3 we use the empirical distribution to calculate the premium when the proportional hazard principle is applied, which leads to a systematic underestimation of the premium. After studying the bias of the premium calculated using this non-parametric approach we take advantage of the bootstrap technique with subsampling to reduce it.
Calculation of LTC Premiums Based on Direct Estimates of Transition Probabilities
Authors: Helms Florian , Czado Claudia , Gschlößl Susanne
Published: November 2005

In this paper we model the life-history of LTC-patients using a Markovian multi-state model in order to calculate premiums for a given LTC-plan. Instead of estimating the transition intensities in this model we use the approach suggested by Andersen et al. (2003) for a direct estimation of the transition probabilities. Based on the Aalen-Johansen estimator, an almost unbiased estimator for the transition matrix of a Markovian multi-state model, we calculate so-called pseudo-values, known from Jackknife methods. Further, we assume that the relationship between these pseudo-values and the covariates of our data are given by a GLM with the logit as link-function. Since the GLMs do not allow for correlation between successive observations we use instead the “Generalized Estimating Equations” (GEEs) to estimate the parameters of our regression model. The approach is illustrated using a representative sample from a German LTC portfolio.
Insurance Capital as a Shared Asset
Authors: Mango Donald
Published: November 2005

Merton and Perold (1993) offered a framework for determining risk capital in a financial firm based on the cost of the implicit guarantee the firm provides to its subsidiaries to make up any operating shortfall. Merton and Perold assume the price of such guarantees is observable from the market at large. For an insurer, this may not be a realistic assumption. This paper proposes an insurance-specific framework for determining the cost of those parental guarantees, and utilizing that cost in pricing and portfolio mix evaluation. An insurer’s capital is treated as a shared asset, with the insurance contracts in the portfolio having simultaneous rights to access potentially all that shared capital. By granting underwriting capacity, an insurer’s management team is implicitly issuing a set of options to draw upon the common capital pool — similar in structure to letters of credit (LOC), except they are not loans but grants. The paper will (i) discuss the valuation of parental guarantees, beginning with Merton and Perold; (ii) treat insurer capital as a shared asset and explore the dual nature of insurer capital usage; (iii) offer a method for determining insurer capital usage cost; and (iv) demonstrate how this method could be used for product pricing and portfolio mix evaluation using economic value added concepts.
Retraction Notice: Emerging Targets for COPD Therapy
Authors: Barnes Peter J.
Published: November 2005

THIS ARTICLE HAS BEEN RETRACTED
Controlled Electrodissolution of Polyelectrolyte Multilayers: A Platform Technology Towards the Surface‐Initiated Delivery of Drugs
Authors: Boulmedais F. , Tang C. S. , Keller B. , Vörös J.
Published: November 2005

A novel method for the electrochemical dissolution of polyelectrolyte multilayers from the surface of an electrode for applications in controlled drug delivery is reported. Biodegradable and biocompatible multilayer films based on poly(L‐lysine) and heparin have been selected as a model system, and have been built on an indium tin oxide semiconductor substrate. The build‐up and dissolution processes of the multilayers is followed by electrochemical optical waveguide light mode spectroscopy. The formation and stability of the polyelectrolyte multilayers have been found to depend on the applied potential and the ionic strength of the buffer. The application of potentials above a threshold of 1.8 V induces dissolution, which follows single‐exponential kinetics, of the polyelectrolyte multilayer film. The rate of this process can be varied by an on–off profile of the potential, leading to the controlled release of heparin into the bulk. Atomic force microscopy investigations show that the electrodissolution of the polyelectrolyte multilayers is a local phenomenon that leads to the formation of nanoporous films.
Metal/Semiconductor Core/Shell Nanodisks and Nanotubes
Authors: Gao P. X. , Lao C. S. , Ding Y. , Wang Z. L.
Published: November 2005

The low melting point of Zn and the high melting point of ZnO, as well as their hexagonal crystal structures, present great advantages for designing and fabricating various metal/semiconductor core/shell nanostructures. By controlling the kinetics in the Zn and ZnO system, the lower‐energy facets, and the oxidation rates of different surfaces, we can control the fabrication of Zn/ZnO core/shell single‐crystal, polycrystalline, and mesoporous nanodisks, as well as a variety of ZnO nanotubes. The oxidation of a Zn nano‐object leads to the formation of Zn/ZnO core/shell nanodisks. A lower oxidation temperature results in the formation of a single‐crystal‐like Zn/ZnO core/shell structure, while a higher oxidation temperature leads to the formation of textured and even polycrystalline nanostructures. A re‐sublimation process of Zn in the core leaves a ZnO shell structure. This is an approach for synthesizing metal/semiconductor core/shell or composite nanostructures. This article offers a detailed description of the kinetics controlling the procedures, the nanostructures obtained, their morphological and crystal structures, and their formation mechanisms.
Superparamagnetic Polymer Nanocomposites with Uniform Fe3O4 Nanoparticle Dispersions
Authors: Gass J. , Poddar P. , Almand J. , Srinath S. , Srikanth H.
Published: November 2005

Magnetic nanoparticles embedded in polymer matrices are good examples of functional nanostructures with excellent potential for applications such as electromagnetic interference shielding, magneto‐optical storage, biomedical sensing, flexible electronics, etc. Control over the dispersion of the nanoparticle phase embedded in a polymer matrix is critical and often challenging. To achieve excellent dispersion, competition between polymer–polymer and polymer–particle interactions have to be balanced to avoid clustering of particles in polymer nanocomposites. We report the first deposition of magnetic nanocomposite poly(methyl methacrylate)/polypyrrole bilayers from solution using spin‐coating. Fe3O4 nanoparticles have been synthesized using a chemical co‐precipitation route. Using a combination of dissolving the polymer and mixing fatty acid surfactant coated Fe3O4 nanoparticles, we have demonstrated the formation of nanocomposites with uniform nanoparticle dispersion. Cross‐sectional scanning electron microscopy, transmission electron microscopy, and magnetic measurements confirm the excellent dispersion and superparamagnetic response. Low‐frequency impedance measurements on these bilayers are also presented and analyzed.
Some New Developments in the Synthesis, Functionalization, and Utilization of Monodisperse Colloidal Spheres
Authors: Jeong U. , Wang Y. , Ibisate M. , Xia Y.
Published: November 2005

This article provides an overview of some recent developments related to the synthesis and functionalization of monodisperse colloidal spheres, a class of colloidal materials that has found widespread use in applications such as the fabrication of photonic crystals, optical sensing, and drug delivery. Traditionally, the choice of materials has been limited to polystyrene and silica. We and other groups have recently expanded the scope of materials by developing a number of methods for producing monodisperse colloidal spheres from various semiconductors and metals. This article is confined to our own work; it covers three different synthetic strategies: the bottom–up approach, the top–down approach, and template‐directed synthesis. The colloidal spheres may have a solid, hollow, or core–shell structure, and the chemical compositions can include Se, Bi, Pb, In, Sn, Cd, Pt, Ag2Se, CdSe, PbS, or TiO2. As an example to illustrate the attractive features of these colloidal spheres, we demonstrate the fabrication of Ag2Se‐based photonic crystals whose stop bands can be thermally switched between two spectral positions.
Role of mathematical modeling on the optimal control of HIV‐1 pathogenesis
Authors: Joly Marcel , Pinto Jose M.
Published: November 2005

Mathematical modeling of HIV‐1 infection has proven to be instrumental for the modern understanding basis of the AIDS pathogenesis, since it offers the unique means to adequately pose hypotheses concerning AIDS dynamics and treatment protocols. Focusing on the HIV‐1 subtype‐B epidemic, a comprehensive review and discussion of the state‐of‐the‐art in the area is presented. Based on recent results, this multidisciplinary study is then extended to a more in‐depth view at the cellular and molecular biology levels that address key issues concerned with the natural history of AIDS, as the basic human anatomic model, the host cell entry of HIV‐1, the quantification the HIV‐1 infectivity in terms of viral coreceptor specificity, as well as regulation and expression of CCR5 and CXCR4 molecules on the target cell, the T‐lymphocyte generation and infection models, and the immune response model. In the sequence, modeling techniques for AIDS pathogenesis are revised and models concerned with either the general HIV‐1 dynamics or specifically related to the HIV‐1 primary infection are discussed. Ultimately, a general framework for the real‐world problem of optimizing the highly active antiretroviral therapy (HAART) benefits is proposed regarding the important questions associated with the drug chemotherapy resistance, side effects and costs. © 2005 American Institute of Chemical Engineers AIChE J, 2006
Atmosphärische Aerosole: Zusammensetzung, Transformation, Klima‐ und Gesundheitseffekte
Authors: Pöschl Ulrich
Published: November 2005

Aerosole sind von zentraler Bedeutung für Chemie und Physik der Atmosphäre sowie für Biosphäre, Klima und Gesundheit. Die luftgetragenen festen und flüssigen Partikel mit Größen im Nanometer‐ und Mikrometerbereich beeinflussen die Energiebilanz der Erde, den Wasserkreislauf und die atmosphärische Zirkulation, aber auch das Vorkommen von Treibhausgasen und reaktiven Spurengasen. Zudem spielen sie wichtige Rollen bei der Fortpflanzung biologischer Organismen und können Erkrankungen auslösen oder verstärken. Die grundlegenden Parameter, die die Umwelt‐ und Gesundheitseffekte von Aerosolpartikeln bestimmen, sind ihre Konzentration, Größe, Struktur und chemische Zusammensetzung. Diese Parameter sind jedoch örtlich und zeitlich hoch variabel. Insbesondere für biologische Partikel und kohlenstoffhaltige Feinstaubkomponenten ist nicht nur die Quantifizierung, sondern auch die Identifizierung eine anspruchsvolle analytische Aufgabe. Dieser Aufsatz umreißt den aktuellen Wissensstand und diskutiert offene Fragen und Forschungsperspektiven zu den Eigenschaften und Wechselwirkungen atmosphärischer Aerosole sowie zu ihren Auswirkungen auf das Klima und die menschliche Gesundheit.
Titelbild: A Phthalocyanine Clathrate of Cubic Symmetry Containing Interconnected Solvent‐Filled Voids of Nanometer Dimensions (Angew. Chem. 46/2005)
Authors: McKeown Neil B. , Makhseed Saad , Msayib Kadhum J. , Ooi Li‐Ling , Helliwell Madeleine , Warren John E.
Published: November 2005

Ein Clathrat aus einem Zinkphthalocyanin hat eine ungewöhnliche Kristallstruktur mit großen solvensgefüllten Hohlräumen (>8 nm3). Der aufgefaltete Würfel auf dem Titelbild zeigt, wie sechs Phthalocyaninmoleküle einen Nanohohlraum aufbauen. Solvensmoleküle, auch Wasser, werden zwischen den Hohlräumen ausgetauscht, und die auf den Flächen befindlichen Metallzentren lassen katalytische Wirkungen erhoffen. Einzelheiten finden sich in der Zuschrift von N. B. McKeown et al. auf S. 7718 ff.
Atmospheric Aerosols: Composition, Transformation, Climate and Health Effects
Authors: Pöschl Ulrich
Published: November 2005

Aerosols are of central importance for atmospheric chemistry and physics, the biosphere, climate, and public health. The airborne solid and liquid particles in the nanometer to micrometer size range influence the energy balance of the Earth, the hydrological cycle, atmospheric circulation, and the abundance of greenhouse and reactive trace gases. Moreover, they play important roles in the reproduction of biological organisms and can cause or enhance diseases. The primary parameters that determine the environmental and health effects of aerosol particles are their concentration, size, structure, and chemical composition. These parameters, however, are spatially and temporally highly variable. The quantification and identification of biological particles and carbonaceous components of fine particulate matter in the air (organic compounds and black or elemental carbon, respectively) represent demanding analytical challenges. This Review outlines the current state of knowledge, major open questions, and research perspectives on the properties and interactions of atmospheric aerosols and their effects on climate and human health.
Reactions of [Ru(CO)3Cl2]2with aromatic nitrogen donor ligands in alcoholic media
Authors: Moreno M. Andreina , Haukka Matti , Kallinen Mirja , Pakkanen Tapani A.
Published: November 2005

The reactions of mono‐ and bidentate aromatic nitrogen‐containing ligands with [Ru(CO)3Cl2]2in alcohols have been studied. In alcoholic media the nitrogen ligands act as bases promoting acidic behaviour of alcohols and the formation of alkoxy carbonyls [Ru(N–N)(CO)2Cl(COOR)] and [Ru(N)2(CO)2Cl(COOR)]. Other products are monomers of type [Ru(N)(CO)3Cl2], bridged complexes such as [Ru(CO)3Cl2]2(N), and ion pairs of the type [Ru(CO)3Cl3]−[Ru(N–N)(CO)3Cl]+(N–N = chelating aromatic nitrogen ligand, N = non‐chelating or bridging ligand). The reaction and the product distribution can be controlled by adjusting the reaction stoichiometry. The reactivity of the new ruthenium complexes was tested in 1‐hexene hydroformylation. The activity can be associated with the degree of stability of the complexes and the ruthenium–ligand interaction. Chelating or bridging nitrogen ligands suppresses the activity strongly compared with the bare ruthenium carbonyl chloride, while the decrease in activity is less pronounced with monodentate ligands. A plausible catalytic cycle is proposed and discussed in terms of ligand–ruthenium interactions. The reactivity of the ligands as well as the catalytic cycle was studied in detail using the computational DFT methods. Copyright © 2005 John Wiley & Sons, Ltd.
Synthesis of Fe‐loaded MFI zeolite using silatrane as precursor and its CO activity
Authors: Kritchayanon N. , Thanabodeekij N. , Jitkarnka S. , Jamieson A. M. , Wongkasemjit S.
Published: November 2005

Fe‐MFI zeolite was successfully synthesized using silatrane as precursor and tetrapropyl ammonium bromide as template via the sol–gel process and microwave heating technique. The effects of ageing time, heating temperature, heating time and iron concentration were investigated, and it was found that Fe‐MFI synthesis favors higher heating temperatures, but is limited by the degradation of the incorporation of a template molecule. Moreover, longer ageing and heating times promote the incorporation of higher amounts of iron atom in the MFI structure. However, too long an ageing time decreases the incorporation of iron. The lower the percentage Fe loading, the greater the percentage of Fe3+ ions incorporated into the MFI framework. The catalytic activity of Fe‐MFI catalyst for the oxidation of CO was studied and it was found that these synthesized catalysts catalyzed the oxidation of CO very well. Copyright © 2005 John Wiley & Sons, Ltd.
Preparation, characterization and biological studies of some novel ferrocenyl compounds
Authors: Abd‐Elzaher Mokhles M. , Ali Ibrahim A. I.
Published: November 2005

Reaction of ferrocene with trichloroacetimidates in the presence of TMSOTf as a catalyst gave a series of novel ferrocenyl compounds, 1–7, in good yield and by a simple method using the Friedel–Crafts reaction. Only monosubstituted ferrocenyl compounds were obtained by flash chromatography at room temperature. Attempts to separate the disubstituted ferrocenyl compounds were unsuccessful, even in the presence of excess (2:1, 3:1 or 4:1) of trichloroacetimidates. The prepared compounds have been characterized by 1H NMR, 13C NMR, IR, UV–vis and mass spectra as well as elemental analysis. The prepared compounds showed medium to good antimicrobial activity against Bacillus subtilis (+ve), Staphylococcus aureus (+ve), Candida albicans (yeast), Escherichia coli (−ve), Salmonella typhi (−ve), Aspergillus niger (fungi) and Fusarium solani (fungi). Copyright © 2005 John Wiley & Sons, Ltd.
1‐Silacyclopent‐2‐enes and 1‐silacyclohex‐2‐enes bearing functionally substituted silyl groups in 2‐positions. Novel electron‐deficient SiHB bridges
Authors: Wrackmeyer Bernd , Tok Oleg L. , Milius Wolfgang , Khan Azim , Badshah Amin
Published: November 2005

The reactions of alkyn‐1‐yl(vinyl)silanes R2Si[CC‐Si(H)Me2]CHCH2 [R = Me (1a), Ph (1b)], Me2Si[CC‐Si(Br)Me2]CHCH2 (2a), and of alkyn‐1‐yl(allyl)silanes R2Si[CC‐Si(H)Me2]CH2CHCH2 (R = Me (3a), R = Ph (3b)] with 9‐borabicyclo[3.3.1]nonane in a 1:1 ratio afford in high yield the 1‐silacyclopent‐2‐ene derivatives 4a, b and 5a, and the 1‐silacyclohex‐2‐ene derivatives 6a, b, respectively, all of which bear a functionally substituted silyl group in 2‐position and the boryl group in 3‐position. This is the result of selective intermolecular 1,2‐hydroboration of the vinyl or allyl group, followed by intramolecular 1,1‐organoboration of the alkynyl group. In the cases of 4a, b, potential electron‐deficient SiHB bridges are absent or extremely weak, whereas in 6a,b the existence of SiHB bridges is evident from the NMR spectroscopic data (1H, 11B, 13C and 29Si NMR). The molecular structure of 4b was determined by X‐ray analysis. Copyright © 2005 John Wiley & Sons, Ltd.
Some principles of regeneration in mammalian systems
Authors: Carlson Bruce M.
Published: November 2005

This article presents some general principles underlying regenerative phenomena in vertebrates, starting with the epimorphic regeneration of the amphibian limb and continuing with tissue and organ regeneration in mammals. Epimorphic regeneration following limb amputation involves wound healing, followed shortly by a phase of dedifferentiation that leads to the formation of a regeneration blastema. Up to the point of blastema formation, dedifferentiation is guided by unique regenerative pathways, but the overall developmental controls underlying limb formation from the blastema generally recapitulate those of embryonic limb development. Damaged mammalian tissues do not form a blastema. At the cellular level, differentiation follows a pattern close to that seen in the embryo, but at the level of the tissue and organ, regeneration is strongly influenced by conditions inherent in the local environment. In some mammalian systems, such as the liver, parenchymal cells contribute progeny to the regenerate. In others, e.g., skeletal muscle and bone, tissue‐specific progenitor cells constitute the main source of regenerating cells. The substrate on which regeneration occurs plays a very important role in determining the course of regeneration. Epimorphic regeneration usually produces an exact replica of the structure that was lost, but in mammalian tissue regeneration the form of the regenerate is largely determined by the mechanical environment acting on the regenerating tissue, and it is normally an imperfect replica of the original. In organ hypertophy, such as that occurring after hepatic resection, the remaining liver mass enlarges, but there is no attempt to restore the original form. Anat Rec (Part B: New Anat) 287B:4–13, 2005. © 2005 Wiley‐Liss, Inc.
Cellular plasticity in vertebrate regeneration
Authors: Odelberg Shannon J.
Published: November 2005

Within the animal kingdom, there are several examples of organisms with remarkable regenerative abilities. Among vertebrates, newts appear to be the most adept at replacing lost structures and injured organs and can regenerate their limbs, tails, spinal cords, jaws, retinas, lenses, optic nerves, intestines, and heart ventricles. This regenerative ability is dependent on the induction of an unusual degree of cellular plasticity near the site of injury. Mature cells lose their differentiated characteristics and revert to proliferating progenitor cells that will later redifferentiate to replace the lost or injured tissues. This degree of cellular plasticity appears to be restricted to those vertebrates with the most remarkable regenerative abilities and is not observed in mammals. However, in the last several years, there have been a few studies suggesting that certain factors present in newt tissues can induce a dedifferentiation response in mammalian cells. These results suggest that the knowledge gained from studying the molecular basis of cellular plasticity in newts and other regeneration‐competent model organisms might one day be used to enhance the regenerative potential in mammals. Anat Rec (Part B: New Anat) 287B:25–35, 2005. © 2005 Wiley‐Liss, Inc.
Peptidyl‐prolyl isomerase inhibitors
Authors: Wang Xiaodong J. , Etzkorn Felicia A.
Published: November 2005

Designed peptidyl‐prolyl isomerase (PPIase) inhibitors of Pin1, cyclophilin (CyP), and FK506 binding protein (FKBP) are reviewed. Emphasis is placed on the design, structure, and biological activity of the inhibitors. While CyP and FKBP inhibitors have been explored fairly thoroughly, inhibitors of the relatively new Pin1 cell cycle regulator are in their infancy. Ligands designed for Pin1 and CyP have primarily been ground state analogues: alkenes and bicyclic compounds. For FKBP, more of the focus has been on analogues of bonds at the reactive center, the prolyl amide, because of the idea that the α‐ketoamide of FK506 is an analogue of the twisted amide in the transition state. © 2005 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 84: 125–146, 2006
An integrated instrumental setup for the combination of atomic force microscopy with optical spectroscopy
Authors: Owen R. J. , Heyes C. D. , Knebel D. , Röcker C. , Nienhaus G. U.
Published: November 2005

In recent years, the study of single biomolecules using fluorescence microscopy and atomic force microscopy (AFM) techniques has resulted in a plethora of new information regarding the physics underlying these complex biological systems. It is especially advantageous to be able to measure the optical, topographical, and mechanical properties of single molecules simultaneously. Here an AFM is used that is especially designed for integration with an inverted optical microscope and that has a near‐infrared light source (850 nm) to eliminate interference between the optical experiment and the AFM operation. The Tip Assisted Optics (TAO) system consists of an additional 100 × 100‐μm2 X–Y scanner for the sample, which can be independently and simultaneously used with the AFM scanner. This allows the offset to be removed between the confocal optical image obtained with the sample scanner and the simultaneously acquired AFM topography image. The tip can be positioned exactly into the optical focus while the user can still navigate within the AFM image for imaging or manipulation of the sample. Thus the tip‐enhancement effect can be maximized and it becomes possible to perform single molecule manipulation experiments within the focus of a confocal optical image. Here this is applied to simultaneous measurement of single quantum dot fluorescence and topography with high spatial resolution. © 2005 Wiley Periodicals, Inc. Biopolymers 82: 410–414, 2006

This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Biologie fluoreszierender Proteine: Ein Regenbogen aus dem Ozean
Authors: Veith Daniel , Veith Martina
Published: November 2005

GFP ist ein fluoreszierendes Quallenprotein, das nach Anregung mit Blaulicht grünes Licht abstrahlt. Für die korrekte Faltung werden weder Substrate noch Cofaktoren benötigt. GFP ist nicht cytotoxisch, sogar ganze Tiere können damit angefärbt werden. Das Anwendungsgebiet von GFP ist sehr groß, weil es in verschiedenen Organismen exprimiert werden kann. Mittlerweile gibt es viele verschiedene GFP‐Varianten, bei denen die für die Fluoreszenz verantwortlichen Aminosäuren mutiert und somit auf unterschiedliche Aspekte hin optimiert wurden. Mit Hilfe der Fluoreszenz können faszinierende Untersuchungen durchgeführt werden. So können die Lokalisation und Dynamik von Proteinen in der lebenden Zelle beispielsweise mit Fusionsproteinen beobachtet werden. Fluoreszierende Proteine finden sich besonders häufig in Nesseltieren, jedoch gibt es nicht‐fluoreszierende Varianten offenbar in allen Tieren. Trotz eines großen natürlichen Farbspektrums stellt Grün eine Art Grundeinstellung dar.
Experimente rund um die Milch: Biotechnologie in der Schule
Authors: Scherr Dietmar , Werel Rainer
Published: November 2005

Milch und Milchprodukte sind ein unerschöpfliches Thema. Will man den Stoffwechsel und seine biotechnologischen Anwendungen in einen Kontext stellen, den die Schülerinnen und Schüler auch von ihrer Umgebung her kennen, dann ergeben sich eine Fülle von interessanten Experimenten und fächerübergreifenden Fragen. Einige wenige, die hauptsächlich den mikrobiologischen Hintergrund beleuchten, wie die Lebendkeimzahlbestimmung und die Fermentation von Milch zu Joghurt und Käse, werden hier aufgezeigt.
Knochenbrecher auf dem Meeresgrund
Authors: Wendler Silke
Published: November 2005

Meeresbiologen haben in der Monterey Bay vor Kalifornien eine neue Symbiose von Polychaeten und Bakterien entdeckt. In 2891 Meter Tiefe haben sie den Kadaver eines jungen Grauwales gefunden, dessen Knochen über und über mit circa ein bis sechs Zentimeter langen Würmern bedeckt waren. Diese Würmer zersetzen anscheinend mit Hilfe von Bakterien das Skelett des verendeten Tieres.
The role of cardiopulmonary fitness and its genetic influences on surgical outcomes
Authors: Lee J T , Chaloner E J , Hollingsworth S J
Published: November 2005

Background

Outcome after major surgery remains poor in some patients. There is an increasing need to identify this cohort and develop strategies to reduce postsurgical morbidity and mortality. Central to outcome is the ability to mount cardiovascular output in response to the increased oxygen demand associated with major surgery.

Methods

A medline search was performed using keywords to identify factors that affect, and genetic influences in, disease and outcome from surgery, and all relevant English language articles published between 1980 and 2005 were retrieved. Secondary references were obtained from key articles.

Results

Preoperative cardiopulmonary exercise testing assesses patient fitness, highlights those at particular risk and, combined with triage to critical care, facilitates significant improvement in surgical outcome. However, genetic factors also influence responses to increased oxygen demand, and some patients are genetically predisposed to mounting increased inflammatory responses, which raise oxygen demand further. Polymorphisms in genes influencing fitness (angiotensin converting enzyme) and immune and inflammatory responses (such as interleukin 6) may associate with surgical outcome.

Conclusions

Development of preoperative screening methods like cardiopulmonary exercise testing and genotype analysis to identify index factors may permit better patient stratification, provide targets for future tailored treatments and so improve surgical outcome.
Local recurrence after curative resection for rectal cancer is associated with anterior position of the tumour
Authors: Chan C L H , Bokey E L , Chapuis P H , Renwick A A , Dent O F
Published: November 2005

Background

Mobilization of rectal cancer can be difficult if the tumour is located anteriorly and may result in a higher incidence of local recurrence. The aim of this study was to determine whether local recurrence and survival following curative resection of rectal cancer were associated with the position of the tumour.

Methods

Data were drawn from a comprehensive, prospective hospital registry of all resections for rectal cancer from January 1990 to December 1998, with follow-up to December 2003.

Results

The 5-year local recurrence rate was 15·9 (95 per cent confidence interval (c.i.) 11·0 to 22·8) per cent in 176 patients with tumours that had an anterior component compared with 5·8 (95 per cent c.i. 2·8 to 11·9) per cent in 132 patients with tumours without an anterior component (P = 0·009). This association persisted after adjustment for other factors linked to local recurrence (hazard ratio (HR) 2·4 (95 per cent c.i. 1·1 to 5·4)). Similarly, anterior position had a significant negative independent association with survival (HR 1·4 (95 per cent c.i. 1·0 to 2·00)).

Conclusion

Anterior position is an independent negative prognostic factor for both local recurrence and survival after curative resection of rectal cancer.
Letter: Systematic review of dressings and topical agents for surgical wounds healing by secondary intention (Br J Surg 2005; 92: 665-672)
Authors: Loefler I
Published: November 2005

The Editors welcome topical correspondence from readers relating to articles published in the Journal. Responses can be sent electronically via the BJS website (http://www.bjs.co.uk) or by post. All letters will be reviewed and, if approved, appear on the website. A selection of these will be edited and published in the Journal. Letters must be no more than 250 words in length. Letters submitted by post should be typed on A4-sized paper in double spacing and should be accompanied by a disk.
Medical student participation in surface anatomy classes
Authors: Aggarwal R. , Brough H. , Ellis H.
Published: November 2005

Surface anatomy is an integral part of medical education and enables medical students to learn skills for future medical practice. In the past decade, there has been a decline in the teaching of anatomy in the medical curriculum, and this study seeks to assess the attitudes of medical students to participation in surface anatomy classes. Consequently, all first year medical students at the Guy's, King's and St Thomas's Medical School, London, were asked to fill in an anonymous questionnaire at the end of their last surface anatomy session of the year. A total of 290 medical students completed the questionnaires, resulting in an 81.6% response rate. The students had a mean age of 19.6 years (range 18–32) and 104 (35.9%) of them were male. Seventy‐six students (26.2%) were subjects in surface anatomy tutorials (60.5% male). Students generally volunteered because no one else did. Of the volunteers, 38.2% would rather not have been subjects, because of embarrassment, inability to make notes, or to see clearly the material being taught. Female medical students from ethnic minority groups were especially reluctant to volunteer to be subjects. Single‐sex classes improved the volunteer rate to some extent, but not dramatically. Students appreciate the importance of surface anatomy to cadaveric study and to future clinical practice. Computer models, lectures, and videos are complementary but cannot be a substitute for peer group models, artists' models being the only alternative. Clin. Anat. 19:627–631, 2006. © 2005 Wiley‐Liss, Inc.
Branching patterns of the common and superficial fibular nerves in fetus
Authors: Kurtoglu Zeliha , Aktekin Mustafa , Uluutku Mehmet Haluk
Published: November 2005

In this study, we focused on finding out whether branching patterns of the common fibular (CFN) and superficial fibular (SFN) nerves change throughout the early period of life. The popliteal fossa and legs on both sides of 20 fetuses (13 females and 7 males) were dissected. The ages of the fetuses varied between 20 and 36 weeks. The levels where the CFN diverged from the sciatic nerve, the CFN diverged to its terminal branches, and the cutaneous branches of the SFN became superficial and diverged were evaluated, together with the similarity of the patterns of these nerves on both sides. We observed that, comparing with the results of previous studies on adults, both the sciatic and the CFNs in the fetuses were diverging into their terminal branches more distally. Additionally, the SFN appeared to become superficial more proximally in the fetus than in the adult. SFN was piercing the crural fascia before diverging into its terminal branches in 29 legs. Only in 8 of them, it was becoming superficial within the middle one‐third of the leg, which was observed more frequently in males (42.9% of 14 legs) than in females (13.3% of 15 legs). But there was no statistically significant gender difference (P = 0.07). The medial dorsal cutaneous (MDCN) and intermediate dorsal cutaneous (IDCN) nerves which were piercing the crural fascia separately were observed in 27.5% of the subjects, all females. In these, MDCN was piercing the fascia superior to the level where the SPN becomes superficial, whereas the IDCN was piercing it to a level lower to this and always in the inferior one‐third of the leg. We suggest that the detailed information about the branching patterns of the CPN and SPN in early ages will be beneficial, particularly in tumor and deformity surgery. The reason for different patterns and piercing levels of the nerves may be the effect of the elongating extremity during aging that enforces the fascia and modifies its position with a more stable structure, the nerve. Clin. Anat. 19:621–626, 2006. © 2005 Wiley‐Liss, Inc.
Applications of the Colorado Visible Human Project in gastroenterology
Authors: Deutsch John C.
Published: November 2005

Several applications of the University of Colorado Visible Human project have recently been developed in clinical gastroenterology, including a textbook of endoscopic ultrasound anatomy, an internet‐based journal, articles on internet web‐sites, and simulators. Details surrounding some of these projects are described. Clin. Anat. 19:254–257, 2006. © 2005 Wiley‐Liss, Inc.
Split spinal cord malformation
Authors: Tubbs R. Shane , Salter E. George , Oakes W. Jerry
Published: November 2005

The split spinal cord is a rare congenital malformation. We report the rare finding of a split cord malformation in a young girl. Further evaluation of this anomaly revealed a Type I split cord malformation (midline bony septation), with no other concomitant pathological entities. Various hypotheses have been made regarding the embryology of this unusual form of spinal dysraphism, and these are reviewed along with the common clinical manifestations of this intriguing pathological entity. Clin. Anat 20:15–18, 2007. © 2005 Wiley‐Liss, Inc.
Magnetic resonance imaging study of cross‐sectional area of the cervical extensor musculature in an asymptomatic cohort
Authors: Elliott J.M. , Jull G.A. , Noteboom J.T. , Durbridge G.L. , Gibbon W.W.
Published: November 2005

Magnetic Resonance Imaging (MRI) can be regarded as the gold standard for muscle imaging; however there is little knowledge about in vivo morphometric features of neck extensor muscles in healthy subjects and how muscle size alters across vertebral segments. It is not known how body size and activity levels may influence neck muscle cross‐sectional area (CSA) or if the muscles differ from left and right. The purpose of this study was to establish relative CSA (rCSA) data for the cervical extensor musculature with a reliable MRI measure in asymptomatic females within a defined age range and to determine if side–side and vertebral level differences exist. MRI of the cervical spine was performed on 42 asymptomatic female subjects within the age range of 18–45. The rCSA values for the cervical extensor muscles were measured from axial T1‐weighted images. We found significant side–side rCSA differences for the rectus capitis posterior minor, major (P < 0.001), multifidus (P = 0.002), and the semispinalis cervicis/capitis (P = 0.001, P < 0.001). There were significant vertebral level differences in rCSA of the semispinalis cervicis/capitis, multifidus, splenius capitis, and upper trapezius (P < 0.001). Activity levels were shown to impact on the size of semispinalis cervicis (P = 0.027), semispinalis capitis (P = 0.003), and the splenius capitis (P = 0.004). In conclusion, measuring differences in neck extensor muscle rCSA with MRI in an asymptomatic population provides the basis for future study investigating relationships between muscular atrophy and symptoms in patients suffering from persistent neck pain. Clin. Anat. 20:35–40, 2007. © 2005 Wiley‐Liss, Inc.
Right‐sided vagus nerve stimulation inhibits induced spinal cord seizures
Authors: Tubbs R. Shane , Salter E. George , Killingsworth Cheryl , Rollins Dennis L. , Smith William M. , Ideker Raymond E. , Wellons John C. , Blount Jeffrey P. , Oakes W. Jerry
Published: November 2005

We have previously shown that left‐sided vagus nerve stimulation results in cessation of induced spinal cord seizures. To test our hypothesis that right‐sided vagus nerve stimulation will also abort seizure activity, we have initiated seizures in the spinal cord and then performed right‐sided vagus nerve stimulation in an animal model. Four pigs were anesthetized and placed in the lateral position and a small laminectomy performed in the lumbar region. Topical penicillin, a known epileptogenic drug to the cerebral cortex and spinal cord, was next applied to the dorsal surface of the exposed cord. With the exception of the control animal, once seizure activity was discernible via motor convulsion or increased electrical activity, the right vagus nerve previously isolated in the neck was stimulated. Following multiple stimulations of the vagus nerve and with seizure activity confirmed, the cord was transected in the midthoracic region and vagus nerve stimulation performed. Right‐sided vagus nerve stimulation resulted in cessation of spinal cord seizure activity in all animals. Transection of the spinal cord superior to the site of seizure induction resulted in the ineffectiveness of vagus nerve stimulation in causing cessation of seizure activity in all study animals. As with left‐sided vagus nerve stimulation, right‐sided vagus nerve stimulation results in cessation of induced spinal cord seizures. Additionally, the effects of right‐sided vagus nerve stimulation on induced spinal cord seizures involve descending spinal pathways. These data may aid in the development of alternative mechanisms for electrical stimulation for patients with medically intractable seizures and add to our knowledge regarding the mechanism for seizure cessation following peripheral nerve stimulation. Clin. Anat. 20:23–26, 2007. © 2005 Wiley‐Liss, Inc.
Partially Reversible Adsorption of Annexin A1 on POPC/POPS Bilayers Investigated by QCM Measurements, SFM, and DMC Simulations
Authors: Kastl Katja , Menke Manuela , Lüthgens Eike , Faiß Simon , Gerke Volker , Janshoff Andreas , Steinem Claudia
Published: November 2005

The kinetics of annexin A1 binding to solid‐supported lipid bilayers consisting of 1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine (POPC)/1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphoserine (POPS; 4:1) has been investigated as a function of the calcium ion concentration in the bulk phase. Quartz crystal microbalance measurements in conjunction with scanning force microscopy, fluorescence microscopy, and computer simulations indicate that at a given Ca2+ concentration annexin A1 adsorbs irreversibly on membrane domains enriched in POPS. By contrast, annexin A1 adsorbs reversibly on the POPC‐enriched phase, which is composed of single POPS molecules embedded within a POPC matrix. The overall area occupied by the POPS‐enriched phase is controlled by the CaCl2 concentration. Monte Carlo simulations suggest that the area of the POPS‐enriched phase increases by a factor of 7 when the Ca2+ concentration is changed from 0.01 to 1 mM.
Assuring the ethical conduct of clinical cancer trials in the developing world
Authors: Markman Maurie
Published: November 2005

It is important that clinical cancer investigators in the “developed” world assist in assuring that cancer trials conducted in the “developing” world satisfy mandatory ethical standards.
FDG‐PET in carcinoma of the uterine cervix with endometrial extension
Authors: Hope Andrew J. , Saha Paban , Grigsby Perry W.
Published: November 2005

BACKGROUND

The authors wished to determine whether pretreatment pathologic evidence of endometrial invasion correlated with fluorine‐18 fluorodeoxyglucose positron emission tomography (FDG‐PET) findings and outcomes in patients with carcinoma of the uterine cervix.

METHODS

Pretreatment whole body FDG‐PET was performed in 58 patients with cervical carcinoma who also underwent pathologic evaluation of the endometrium by biopsy or dilation and curettage. FDG‐PET lymph node status, disease free survival, and overall survival were evaluated.

RESULTS

Thirty seven (64%) patients had pathologic evidence of endometrial invasion. Pelvic lymph node metastases were three times more frequent in patients with evidence of endometrial invasion compared with those without endometrial invasion (70% vs. 23%,P< 0.001). Patients with endometrial invasion also had a significantly increased risk of paraaortic and supraclavicular lymph node metastases at presentation (30% vs. 0%P= 0.006). Endometrial invasion was associated with a decreased 2‐year disease‐free survival (78% vs. 58%,P= 0.046) and overall survival (92% vs. 65%,P=0.047).

CONCLUSIONS

Endometrial extension in cervical cancer correlated strongly with risk of FDG‐PET detected lymph node metastases in this study's population and was associated with a poor prognosis. Cancer 2006. © 2005 American Cancer Society.
Core‐stateless fair rate estimation fair queuing
Authors: Li Jung‐Shian , Lin Yi‐Ting , Yang Ching‐Fang
Published: November 2005

Core‐stateless mechanisms, such as core‐stateless fair queuing (CSFQ), reduce the complexity of fair queuing, which usually need to maintain states, manage buffers, and perform flow scheduling on a per‐flow basis. However, they require executing label rewriting and dropping decision on a per‐packet basis, thus preventing them from being widely deployed. In this paper, we propose a novel architecture based on CSFQ without per‐packet labelling. Similarly, we distinguish between edge routers and core routers. Edge routers maintain the per‐flow state by employing a fair queuing mechanism to allocate each flow a fair bandwidth share locally and a token bucket mechanism to regulate those flows with feedback packets sent from egress edge routers. Core routers do not maintain per‐flow state; they use FIFO packet scheduling extended by a fare rate alarm mechanism by estimating the arrival rate and the number of flows using a matching–mismatching algorithm. The novel scheme is called core‐stateless fair rate estimation fair queuing (CSFREFQ). CSFREFQ is proven to be capable of achieving max–min fairness. Furthermore, we present and discuss simulations and experiments on the performance under different traffic scenarios. Copyright © 2005 John Wiley & Sons, Ltd.