bluuebunny/crossref_metadata_2025 huggingface dataset:
Functionally Distinct LAG-3 and PD-1 Subsets on Activated and Chronically Stimulated CD8 T Cells
Authors: Grosso Joseph F. , Goldberg Monica V. , Getnet Derese , Bruno Tullia C. , Yen Hung-Rong , Pyle Kristin J. , Hipkiss Edward , Vignali Dario A. A. , Pardoll Drew M. , Drake Charles G.
Published: May 2009

Lymphocyte Activation Gene-3 (LAG-3) is a transmembrane protein that binds MHC class II, enhances regulatory T cell activity, and negatively regulates cellular proliferation, activation, and homeostasis of T cells. Programmed Death 1 (PD-1) also negatively regulates T cell function. LAG-3 and PD-1 are both transiently expressed on CD8 T cells that have been stimulated during acute activation. However, both LAG-3 and PD-1 remain on CD8 T cells at high levels after stimulation within tolerizing environments. Our previous data demonstrated that blockade of either LAG-3 or PD-1 using mAb therapy in combination with vaccination restores the function of tolerized Ag-specific CD8 T cells in models of self and tumor tolerance. It is unclear whether tolerized CD8 T cells coexpress PD-1 and LAG-3 or whether PD-1 and LAG-3 mark functionally distinct populations of CD8 T cells. In this study, we describe three populations of CD8 T cells activated under tolerizing conditions based on LAG-3 and PD-1 staining, each with distinct phenotypic and functional characteristics. From a mechanistic perspective, both Ag concentration and proinflammatory signals control the expression of LAG-3 and PD-1 phenotypes on CD8 T cells under activating and tolerizing conditions. These results imply that signaling through the PD-1 and LAG-3 pathways have distinct functional consequences to CD8 T cells under tolerizing conditions and manipulation of both Ag and cytokine signaling can influence CD8 tolerance through LAG-3 and PD-1.
Antiviral Antibodies Target Adenovirus to Phagolysosomes and Amplify the Innate Immune Response
Authors: Zaiss Anne K. , Vilaysane Akosua , Cotter Matthew J. , Clark Sharon A. , Meijndert H. Christopher , Colarusso Pina , Yates Robin M. , Petrilli Virginie , Tschopp Jurg , Muruve Daniel A.
Published: May 2009

Adenovirus is a nonenveloped dsDNA virus that activates intracellular innate immune pathways. In vivo, adenovirus-immunized mice displayed an enhanced innate immune response and diminished virus-mediated gene delivery following challenge with the adenovirus vector AdLacZ suggesting that antiviral Abs modulate viral interactions with innate immune cells. Under naive serum conditions in vitro, adenovirus binding and internalization in macrophages and the subsequent activation of innate immune mechanisms were inefficient. In contrast to the neutralizing effect observed in nonhematopoietic cells, adenovirus infection in the presence of antiviral Abs significantly increased FcR-dependent viral internalization in macrophages. In direct correlation with the increased viral internalization, antiviral Abs amplified the innate immune response to adenovirus as determined by the expression of NF-κB-dependent genes, type I IFNs, and caspase-dependent IL-1β maturation. Immune serum amplified TLR9-independent type I IFN expression and enhanced NLRP3-dependent IL-1β maturation in response to adenovirus, confirming that antiviral Abs specifically amplify intracellular innate pathways. In the presence of Abs, confocal microscopy demonstrated increased targeting of adenovirus to LAMP1-positive phagolysosomes in macrophages but not epithelial cells. These data show that antiviral Abs subvert natural viral tropism and target the adenovirus to phagolysosomes and the intracellular innate immune system in macrophages. Furthermore, these results illustrate a cross-talk where the adaptive immune system positively regulates the innate immune system and the antiviral state.
Lipoproteins in Staphylococcus aureus Mediate Inflammation by TLR2 and Iron-Dependent Growth In Vivo
Authors: Schmaler Mathias , Jann Naja J. , Ferracin Fabrizia , Landolt Lea Z. , Biswas Lalitha , Götz Friedrich , Landmann Regine
Published: May 2009

Lipoproteins (Lpp) are ligands of TLR2 and signal by the adaptor MyD88. As part of the bacterial cell envelope, Lpp are mainly involved in nutrient acquisition for Staphylococcus aureus. The impact of Lpp on TLR2-MyD88 activation for S. aureus in systemic infection is unknown. S. aureus strain SA113 deficient in the enzyme encoded by the prolipoprotein diacylglyceryl transferase gene (Δlgt), which attaches the lipid anchor to pro-Lpp, was used to study benefits and costs of Lpp maturation. Lpp in S. aureus induced early and strong cytokines by TLR2-MyD88 signaling in murine peritoneal macrophages. Lpp contributed via TLR2 to pathogenesis of sepsis in C57BL/6 mice with IL-1β, chemokine-mediated inflammation, and high bacterial numbers. In the absence of MyD88-mediated inflammation, Lpp allowed bacterial clearing from liver devoid of infiltrating cells, but still conferred a strong growth advantage in mice, which was shown to rely on iron uptake and storage in vitro and in vivo. With iron-restricted bacteria, the Lpp-related growth advantage was evident in infection of MyD88−/−, but not of C57BL/6, mice. On the other hand, iron overload of the host restored the growth deficit of Δlgt in MyD88−/−, but not in immunocompetent C57BL/6 mice. These results indicate that iron acquisition is improved by Lpp of S. aureus but is counteracted by inflammation. Thus, lipid anchoring is an evolutionary advantage for S. aureus to retain essential proteins for better survival in infection.
CD27 Expression on CD4+ T Cells Differentiates Effector from Regulatory T Cell Subsets in the Lung
Authors: Mack Douglas G. , Lanham Allison M. , Palmer Brent E. , Maier Lisa A. , Fontenot Andrew P.
Published: May 2009

Beryllium exposure in the workplace can result in chronic beryllium disease, a granulomatous lung disorder characterized by CD4+ T cell alveolitis and progressive lung fibrosis. A large number of the CD4+ T cells recruited to the lung in chronic beryllium disease recognize beryllium in an Ag-specific manner and express Th1-type cytokines following T cell activation. Beryllium-responsive CD4+ T cells in the bronchoalveolar lavage (BAL) express an effector memory T cell phenotype and recognize beryllium in a CD28-independent manner. In this study, we show that the majority of beryllium-responsive CD4+ T cells in BAL have lost CD27 expression, whereas a subset of beryllium-responsive cells in blood retains expression of this costimulatory molecule. In addition, loss of CD27 on BAL CD4+ T cells inversely correlates with markers of lung inflammation. A small population of BAL CD4+ T cells retains CD27 expression, and these CD4+CD27+ T cells contain the FoxP3-expressing, naturally occurring regulatory T (Treg) cell subset. Coexpression of CD27 and CD25 identifies the majority of FoxP3-expressing Treg cells in blood and BAL, and these cells express potent suppressor function. Taken together, these findings suggest that CD27 is differentially expressed between effector T cells from the inflamed lung and can be used in conjunction with CD25 to isolate Treg cells and assess their functional capacity in an ongoing adaptive immune response in a target organ.
Inhibition and Genetic Deficiency of p38 MAPK Up-Regulates Heme Oxygenase-1 Gene Expression via Nrf2
Authors: Naidu Srivatsava , Vijayan Vijith , Santoso Sentot , Kietzmann Thomas , Immenschuh Stephan
Published: May 2009

Heme oxygenase (HO)-1 is the inducible isoform of the first and rate-limiting enzyme of heme degradation. The HO products carbon monoxide and bilirubin not only provide antioxidant cytoprotection, but also have potent anti-inflammatory and immunomodulatory functions. Although HO-1 has previously been shown to be induced by various stimuli via activation of the p38 MAPK signaling pathway, the role of this protein kinase for HO-1 gene regulation is largely unknown. In the present study, it is demonstrated that pharmacological inhibitors of p38 induced HO-1 expression in monocytic cells. Moreover, basal HO-1 gene expression levels were markedly higher in untreated murine embryonic fibroblasts (MEF) from p38α−/− mice compared with those from wild-type mice. Transfection studies with luciferase reporter gene constructs indicate that increased HO-1 gene expression via inhibition of p38 was mediated by the transcription factor Nrf2, which is a central regulator of the cellular oxidative stress response. Accordingly, inhibitors of p38 induced binding of nuclear proteins to a Nrf2 target sequence of the HO-1 promoter, but did not affect HO-1 protein expression and promoter activity in Nrf2−/− MEF. Genetic deficiency of p38 led to enhanced phosphorylation of ERK and increased cellular accumulation of reactive oxygen species. In addition, pharmacological blockage of ERK and scavenging of reactive oxygen species with N-acetylcysteine reduced HO-1 gene expression in p38−/− MEF, respectively. Taken together, it is demonstrated that pharmacological inhibition and genetic deficiency of p38 induce HO-1 gene expression via a Nrf2-dependent mechanism in monocytic cells and MEF.
Osteopontin Enhances Phagocytosis through a Novel Osteopontin Receptor, the αXβ2 Integrin
Authors: Schack Lotte , Stapulionis Romualdas , Christensen Brian , Kofod-Olsen Emil , Skov Sørensen Uffe B. , Vorup-Jensen Thomas , Sørensen Esben S. , Höllsberg Per
Published: May 2009

Osteopontin (OPN) is a cytokine with multiple functions, including immune defense mechanisms against invading microorganisms. OPN-deficient mice are impaired in clearing intracellular pathogens, suggesting an important role of OPN during phagocytosis, but it remains to be defined how OPN may enhance this innate immune process. Here, we demonstrate that OPN binds to monocytes, but not resting T cells, NK cells, or B cells, and mediates chemoattraction of IL-1-activated human monocytes. Moreover, OPN binds in a specific manner to all known serotypes of the two bacterial species Streptococcus agalactiae and Staphylococcus aureus and opsonizes these bacteria for phagocytosis. We identify the integrin αXβ2 (CD11c/CD18), which is highly expressed on the cell surface of monocytes, as a novel OPN receptor. To eliminate the contribution from other molecular interactions between the bacteria and the phagocyte, we show that OPN-coated synthetic beads are phagocytosed in an αXβ2 integrin-dependent manner. The ligand recognition does not involve the RGD motif previously reported to support binding of OPN to integrins. Taken together, these data identify the αXβ2 integrin as a novel OPN receptor that is required for OPN-mediated phagocytosis, thereby elucidating an important mechanism of an innate immune function of OPN.
Ig Synthesis and Class Switching Do Not Require the Presence of the hs4 Enhancer in the 3′ IgH Regulatory Region
Authors: Vincent-Fabert Christelle , Truffinet Véronique , Fiancette Remi , Cogné Nadine , Cogné Michel , Denizot Yves
Published: May 2009

Several studies have reported that regulatory elements located 3′ of the IgH locus (namely hs3a, hs1,2, hs3b, and hs4) might play a role during class switch recombination (CSR) and Ig synthesis. While individual deletion of hs3a or hs1,2 had no effect, pairwise deletion of hs3b (an inverted copy of hs3a) and hs4 markedly affected CSR and Ig expression. Among these two elements, hs4 was tentatively presented with the master role due to its unique status within the 3′ regulatory region: distal position outside repeated regions, early activation in pre-B cells, strong activity throughout B cell ontogeny. To clarify its role, we generated mice with a clean deletion of the hs4 after replacement with a floxed neoR cassette. Surprisingly, and as for previous deletion of hs3a or hs1,2, deletion of hs4 did not affect either in vivo CSR or the secretion level of any Ig isotype. In vitro CSR and Ig secretion in response to LPS and cytokines was not affected either. The only noticeable effects of the hs4 deletion were a decrease in the number of B splenocytes and a decreased membrane IgM expression. In conclusion, while dispensable for CSR and Ig transcription in plasma cells, hs4 mostly appears to contribute to Ig transcription in resting B lymphocytes.
Control of Thymic T Cell Maturation, Deletion and Egress by the RNA-Binding Protein HuR
Authors: Papadaki Olympia , Milatos Stavros , Grammenoudi Sofia , Mukherjee Neelanjan , Keene Jack D. , Kontoyiannis Dimitris L.
Published: May 2009

HuR emerged as a posttranscriptional regulator of mRNAs involved in cellular control, stress, and immunity but its role in governing such responses remains elusive. In this study, we assessed HuR’s role in the staged progression of thymic T cell differentiation by means of its genetic ablation. Mice with an early deletion of HuR in thymocytes possess enlarged thymi but display a substantial loss of peripheral T cells. We show that this discordant phenotype related to specific defects in thymic cellular processes, which demonstrated HuR’s involvement in: 1) intrinsic checkpoint signals suppressing the cell cycle of immature thymocyte progenitors, 2) TCR and antigenic signals promoting the activation and positive selection of mature thymocytes, 3) antigenic and death-receptor signals promoting thymocyte deletion, and 4) chemokine signals driving the egress of postselection thymocytes to the periphery. The cellular consequences of HuR’s dysfunction were underlined by the aberrant expression of selective cell cycle regulators, TCR, and death-receptor signaling components. Our studies reveal the signal-dependent context of HuR’s cellular activities in thymocytes and its importance in the generation of a physiological T cell pool.
Psychological testing: An introduction (2nd edition)
Authors: Pillay Shanya
Published: May 2009

The book under review provides a comprehensive introduction to psychological testing. It is divided into five parts, each dealing with a different aspect of testing. Part 1 looks at basic issues surrounding psychological testing. It addresses issues such as the nature of tests, test administration and reliability and validity issues. Generally, the information provided in Part 1 is clear - however, given that these sections essentially introduce the reader to the subject area of psychological testing, it could have been more thorough.
Lithiumdotierung eines hydroxymodifizierten MIL‐53‐Strukturanalogons zur Verbesserung der Wasserstoffadsorption
Authors: Himsl Dieter , Wallacher Dirk , Hartmann Martin
Published: May 2009

Eine einfache Strategie für die Herstellung eines lithiumdotierten, porösen, metall‐organischen Gerüsts (MOF; siehe Struktur; schwarz C, rot O, blau AlO6‐Oktaeder) wurde entwickelt, die den Weg zur Synthese weiterer Mitglieder dieser Stoffklasse ebnet. In Übereinstimmung mit Vorhersagen adsorbierte das untersuchte dotierte MOF Wasserstoff deutlich besser als sein undotiertes Gegenstück.

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Interaction and Reaction of the Phenyl Radical with Water: A Source of OH Radicals
Authors: Mardyukov Artur , Sanchez‐Garcia Elsa , Crespo‐Otero Rachel , Sander Wolfram
Published: May 2009

Das ist radikal! Bei einer photochemischen Reaktion zwischen Phenylradikal und Wasser wird ein Wasserstoffatom aus Wasser abstrahiert und ein Hydroxylradikal gebildet. Das Hydroxylradikal geht mit Benzol eine OH⋅⋅⋅π‐Wasserstoffbrücke ein (siehe Bild) und reagiert mit Benzol unter Matrixisolationsbedingungen nicht thermisch.

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Kooperative Molekülbewegungen innerhalb eines selbstorganisierten flüssigkristallinen molekularen Drahtes am Beispiel eines TEG‐ substituierten Perylendiimids
Authors: Hansen Michael Ryan , Schnitzler Tobias , Pisula Wojciech , Graf Robert , Müllen Klaus , Spiess Hans Wolfgang
Published: May 2009

Immer in Bewegung bleiben! Die Moleküldynamik von Perylengrundkörpern in kolumnaren Strukturen beeinflusst die Prozessierbarkeit und die Selbstheilung solcher Systeme. Eine Kombination von Röntgenstreuung und Festkörper‐NMR‐Spektroskopie zeigte, dass selbst im eingefrorenen Zustand lokal beschränkte Fluktuationen der Kerne möglich sind und in der flüssigkristallinen Phase hoch kooperative, spiralartige Bewegungen stattfinden (siehe Bild).

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Miniemulsionspolymerisation und Struktur von Polymer‐ und Hybridnanopartikeln
Authors: Landfester Katharina
Published: May 2009

Maximaler Erfolg dank Miniemulsion: Der Miniemulsionsprozess ermöglicht die Bildung komplexer Polymernanopartikel und die Verkapselung unterschiedlichster Materialien in einer Polyschale (siehe Beispiele). Eine Funktionalisierung der Nanopartikel gelingt einfach. Polymerisationen zur Erzeugung von Polymernanopartikeln gelingen in umweltfreundlichen Lösungsmitteln wie H2O.

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Der Miniemulsionsprozess ermöglicht die Bildung von komplexen polymeren Nanopartikeln und die Verkapselung eines festen oder flüssigen, eines anorganischen oder organischen, eines hydrophoben oder hydrophilen Materials in einer Polyschale. Dabei lassen sich verschiedenste Materialien von organischen und anorganischen Pigmenten, Magnetit oder anderen festen Nanopartikeln bis hin zu hydrophilen oder hydrophoben Flüssigkeiten wie Duftstoffen, Medikamenten oder Photoinitiatoren verkapseln. Eine Funktionalisierung der Nanopartikel kann einfach erzielt werden. Ein Vorteil gegenüber Polymerisationsprozessen in organischen Lösungsmitteln ist die Tatsache, dass Polymerisationen zum Erhalt polymerer Nanopartikel in umweltfreundlichen Lösungsmitteln, meistens Wasser, durchgeführt werden können.
Practical Synthesis of the Dendralene Family Reveals Alternation in Behavior
Authors: Payne Alan D. , Bojase Gomotsang , Paddon‐Row Michael N. , Sherburn Michael S.
Published: May 2009

Nicht länger obskur: Eine brauchbare Synthese der ersten sechs Mitglieder der fundamentalen Klasse der acyclischen verzweigten Oligoalkene ist gelungen. Auf diesem Weg sind die Zielverbindungen in guten Ausbeuten im Multigramm‐Maßstab zugänglich. Verbindungen mit einer geraden Zahl an Doppelbindungen sind deutlich stabiler als die mit einer ungeraden Zahl (siehe Bild), und sie unterscheiden sich im Reaktionsverhalten bei Diels‐Alder‐Reaktionen.

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Innentitelbild: Matrix‐Free Formation of Gas‐Phase Biomolecular Ions by Soft Cluster‐Induced Desorption (Angew. Chem. 23/2009)
Authors: Gebhardt Christoph. R. , Tomsic Anna , Schröder Hartmut , Dürr Michael , Kompa Karl L.
Published: May 2009

Die Massenspektrometrie von Biomolekülen hat sich zu einer Schlüsseltechnik in der Bioanalytik entwickelt. Wie C. R. Gebhardt, M. Dürr und Mitarbeiter in ihrer Zuschrift auf S. 4226 ff. beschreiben, kann das Aufprallen neutraler molekularer Cluster auf einer Oberfläche zur „sanften“ Bildung von Biomolekül‐Ionen genutzt werden. Durch den Aufprall auf die Oberfläche liefern die Cluster die Energie, die für die Desorption der adsorbierten Biomoleküle benötigt wird, und sie dienen zugleich als transiente Matrix. Nachfolgende Verdunstungskühlung verhindert die Fragmentierung und führt schließlich zu einem isolierten Biomolekül‐Ion in der Gasphase.

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Improving the Hydrogen‐Adsorption Properties of a Hydroxy‐Modified MIL‐53(Al) Structural Analogue by Lithium Doping
Authors: Himsl Dieter , Wallacher Dirk , Hartmann Martin
Published: May 2009

Lithium makes the difference: A simple strategy for the synthesis of lithium‐doped porous metal–organic frameworks (MOFs) is developed (see structure; C black, O red, AlO6 blue octahedra), thus paving the way for the facile preparation of lithium‐doped MOFs. Moreover, the significant increase in hydrogen adsorption predicted by theoretical calculations is observed.

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Miniemulsion Polymerization and the Structure of Polymer and Hybrid Nanoparticles
Authors: Landfester Katharina
Published: May 2009

The miniemulsion process allows the formation of complex polymer nanoparticles and the encapsulation of widely varying materials into a polymer shell (see examples). Functionalization of the nanoparticles can be easily carried out, and polymerization to form polymer nanoparticles can be performed in environmentally friendly solvents, such as water.

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The miniemulsion process allows the formation of complex structured polymeric nanoparticles and the encapsulation of a solid or liquid, an inorganic or organic, or a hydrophobic or hydrophilic material into a polymer shell. Many different materials, ranging from organic and inorganic pigments, magnetite, or other solid nanoparticles, to hydrophobic and hydrophilic liquids, such as fragrances, drugs, or photoinitators, can be encapsulated. Functionalization of the nanoparticles can also be easily obtained. Compared to polymerization processes in organic solvents, polymerization to obtain polymeric nanoparticles can be performed in environmentally friendly solvents, usually water.
Tin Chemistry.Fundamentals, Frontiers, and Applications. Edited by Alwyn G. Davies, Marcel Gielen, Keith H. Pannell and Edward R. T. Tiekink.
Authors: Dehnen Stefanie
Published: May 2009

John Wiley & Sons, Chichester 2008. 752 pp., hardcover € 199.00.—ISBN 978‐0470517710

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Indirect Optical Analysis of a Dynamic Chemical System
Authors: Gasparini Giulio , Bettin Federico , Scrimin Paolo , Prins Leonard J.
Published: May 2009

Hide and seek: The composition of a dynamic covalent equilibrium reaction is determined by measuring the ‘left‐over’ concentration of a reference compound (blue object, see picture). Reaction of the reference compound with a scavenger generates a characteristic UV/Vis signal that is independent of the molecular structure of the target.

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9,10‐Dihydro‐9,10‐diboraanthracene: Supramolecular Structure and Use as a Building Block for Luminescent Conjugated Polymers
Authors: Lorbach Andreas , Bolte Michael , Li Haiyan , Lerner Hans‐Wolfram , Holthausen Max C. , Jäkle Frieder , Wagner Matthias
Published: May 2009

Building bridges: The title compound forms an unprecedented polymeric structure with bridging B–H–B three‐center two‐electron bonds in the solid state. This organoborane serves as an efficient precursor for the preparation of boron‐doped π‐conjugated polymers by hydroboration polymerization with a functionalized 1,4‐diethynylbenzene (see picture). These polymers form thin films that show intense green luminescence.

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A study of the Coriolis effect on the fluid flow profile in a centrifugal bioreactor
Authors: Detzel Christopher J. , Thorson Michael R. , Van Wie Bernard J. , Ivory Cornelius F.
Published: May 2009

Increasing demand for tissues, proteins, and antibodies derived from cell culture is necessitating the development and implementation of high cell density bioreactors. A system for studying high density culture is the centrifugal bioreactor (CCBR), which retains cells by increasing settling velocities through system rotation, thereby eliminating diffusional limitations associated with mechanical cell retention devices. This article focuses on the fluid mechanics of the CCBR system by considering Coriolis effects. Such considerations for centrifugal bioprocessing have heretofore been ignored; therefore, a simpler analysis of an empty chamber will be performed. Comparisons are made between numerical simulations and bromophenol blue dye injection experiments. For the non‐rotating bioreactor with an inlet velocity of 4.3 cm/s, both the numerical and experimental results show the formation of a teardrop shaped plume of dye following streamlines through the reactor. However, as the reactor is rotated, the simulation predicts the development of vortices and a flow profile dominated by Coriolis forces resulting in the majority of flow up the leading wall of the reactor as dye initially enters the chamber, results are confirmed by experimental observations. As the reactor continues to fill with dye, the simulation predicts dye movement up both walls while experimental observations show the reactor fills with dye from the exit to the inlet. Differences between the simulation and experimental observations can be explained by excessive diffusion required for simulation convergence, and a slight density difference between dyed and un‐dyed solutions. Implications of the results on practical bioreactor use are also discussed. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
Controllable microfluidic synthesis of multiphase drug‐carrying lipospheres for site‐targeted therapy
Authors: Hettiarachchi Kanaka , Zhang Shirley , Feingold Steven , Lee Abraham P. , Dayton Paul A.
Published: May 2009

We report the production of micrometer‐sized gas‐filled lipospheres using digital (droplet‐based) microfluidics technology for chemotherapeutic drug delivery. Advantages of on‐chip synthesis include a monodisperse size distribution (polydispersity index (σ) values of <5%) with consistent stability and uniform drug loading. Photolithography techniques are applied to fabricate novel PDMS‐based microfluidic devices that feature a combined dual hydrodynamic flow‐focusing region and expanding nozzle geometry with a narrow orifice. Spherical vehicles are formed through flow‐focusing by the self‐assembly of phospholipids to a lipid layer around the gas core, followed by a shear‐induced break off at the orifice. The encapsulation of an extra oil layer between the outer lipid shell and inner bubble gaseous core allows the transport of highly hydrophobic and toxic drugs at high concentrations. Doxorubicin (Dox) entrapment is estimated at 15 mg mL−1 of particles packed in a single ordered layer. In addition, the attachment of targeting ligands to the lipid shell allows for direct vehicle binding to cancer cells. Preliminary acoustic studies of these monodisperse gas lipospheres reveal a highly uniform echo correlation of greater than 95%. The potential exists for localized drug concentration and release with ultrasound energy. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009
A first‐in‐man study of the reitan catheter pump for circulatory support in patients undergoing high‐risk percutaneous coronary intervention
Authors: Smith Elliot J. , Reitan Oyvind , Keeble Thomas , Dixon Kerry , Rothman Martin T.
Published: May 2009

Objectives: To investigate the safety of a novel percutaneous circulatory support device during high‐risk percutaneous coronary intervention (PCI). Background: The Reitan catheter pump (RCP) consists of a catheter‐mounted pump‐head with a foldable propeller and surrounding cage. Positioned in the descending aorta the pump creates a pressure gradient, reducing afterload and enhancing organ perfusion. Methods: Ten consecutive patients requiring circulatory support underwent PCI; mean age 71 ± 9; LVEF 34% ± 11%; jeopardy score 8 ± 2.3. The RCP was inserted via the femoral artery. Hemostasis was achieved using Perclose™ sutures. PCI was performed via the radial artery. Outcomes included in‐hospital death, MI, stroke, and vascular injury. Hemoglobin (Hb), free plasma Hb (fHb), platelets, and creatinine (cre) were measured pre PCI and post RCP removal. Results: The pump was inserted and operated successfully in 9/10 cases (median 79 min). Propeller rotation at 10,444 ± 1,424 rpm maintained an aortic gradient of 9.8 ± 2 mm Hg. Although fHb increased, there was no significant hemolysis (4.7 ± 2.4 mg/dl pre vs. 11.9 ± 10.5 post, P = 0.04, reference 20 mg/dl). Platelets were unchanged (pre 257 ± 74 × 109 vs. 245 ± 63, P = NS). Renal function improved (cre pre 110 ± 27 μmol/l vs. 99 ± 28, P = 0.004). The RCP was not used in one patient following femoral introducer sheath related aortic dissection. All PCI procedures were successful with no deaths or strokes, one MI, and no vascular complications following pump removal. Conclusions: The RCP can be used safely in high‐risk PCI patients. This device may be an alternative to other percutaneous systems when substantial cardiac support is needed. © 2009 Wiley‐Liss, Inc.
The argument for aggressive coiling of aortopulmonary collaterals in single ventricle patients
Authors: Stern Herbert J.
Published: May 2009

Aortopulmonary collaterals are present in up to 80% of single ventricle anatomy patients undergoing pre‐Fontan catheterization. There is generally no consensus as to their impact in the mid‐long term course of these patients. We present arguments that aggressive coiling of these vessels is warranted to prevent deterioration of ventricular function long‐term. Non‐invasive modalities for measuring APC are needed. Multi‐institutional, prospective, randomized, double blind studies are also needed to confirm our hypotheses. © 2009 Wiley‐Liss, Inc.
Crossing CTOs—The tips, tricks, and specialist Kit that can mean the difference between success and failure
Authors: Godino Cosmo , Sharp Andrew S.P. , Carlino Mauro , Colombo Antonio
Published: May 2009

Percutaneous coronary intervention (PCI) for chronic total occlusions (CTO) remains one of the major challenges in interventional cardiology. The appropriate use of the rapidly increasing range of tools available to interventional cardiologists is bringing more and more CTOs into the ‘treatable’ category. The bar has now been raised to 80% success rates by some expert operators around the world, which, in our view, cannot be achieved without a thorough understanding of technique and technical know‐how. CTO procedures are increasingly becoming a sub‐specialist field within interventional cardiology and we would encourage centers to consider appointing ‘super‐specialists’ who are able to concentrate experience and expertise in this area. In this paper we detail the principal characteristics of the over the wire balloons, microcatheters and guidewires at present available, the most popular and recent of which are listed in Table 1 and 2. The knowledge and the specific choice of these materials and the criteria for selection of your guidewire or microcatheter can mean the difference between success and failure. Moreover, we discuss on the most important and groundbreaking techniques to approach a CTO. Finally, considering the greater risk of coronary perforation related to a CTO procedure compared to routine PCI, we describe which are best strategy and devices for treating coronary perforations and other major complications. © 2009 Wiley‐Liss, Inc.
Immobilization and chiral recognition of 3,5‐dimethylphenylcarbamates of cellulose and amylose bearing 4‐(trimethoxysilyl)phenylcarbamate groups
Authors: Tang Shouwan , Ikai Tomoyuki , Tsuji Masashi , Okamoto Yoshio
Published: May 2009

A small amount of 4‐(trimethoxysilyl)phenyl groups was randomly introduced onto the 3,5‐dimethylphenylcarbamates of cellulose and amylose by a one‐pot method. The obtained derivatives were then effectively immobilized onto silica gel as chiral packing materials (CPMs) for high‐performance liquid chromatography through intermolecular polycondensation of the trimethoxysilyl groups. The effects of the amount of 4‐(trimethoxysilyl)phenyl groups on immobilization and enantioseparation were investigated. Also, the solvent durability of the immobilized‐type CPMs was examined with the eluents containing chloroform and tetrahydrofuran. When these eluents were used, the chiral recognition abilities of the CPMs for most of the tested racemates were improved to some extent depending on the compounds. Chirality 2010. © 2009 Wiley‐Liss, Inc.
On the incidence–prevalence relation and length‐biased sampling
Authors: Addona Vittorio , Asgharian Masoud , Wolfson David B.
Published: May 2009

For many diseases, logistic constraints render large incidence studies difficult to carry out. This becomes a drawback, particularly when a new study is needed each time the incidence rate is investigated in a new population. By carrying out a prevalent cohort study with follow‐up it is possible to estimate the incidence rate if it is constant. The authors derive the maximum likelihood estimator (MLE) of the overall incidence rate, λ, as well as age‐specific incidence rates, by exploiting the epidemiologic relationship, (prevalence odds) = (incidence rate) × (mean duration) (P/[1 − P] = λ × µ). The authors establish the asymptotic distributions of the MLEs and provide approximate confidence intervals for the parameters. Moreover, the MLE of λ is asymptotically most efficient and is the natural estimator obtained by substituting the marginal maximum likelihood estimators for P and µ into P/[1 − P] = λ × µ. Following‐up the subjects allows the authors to develop these widely applicable procedures. The authors apply their methods to data collected as part of the Canadian Study of Health and Ageing to estimate the incidence rate of dementia amongst elderly Canadians. The Canadian Journal of Statistics © 2009 Statistical Society of Canada
A practical method for analysing heavy tailed data
Authors: Peng Liang
Published: May 2009

An important practical issue of applying heavy tailed distributions is how to choose the sample fraction or threshold, since only a fraction of upper order statistics can be employed in the inference. Recently, Guillou & Hall (2001; Journal of Royal Statistical Society B, 63, 293–305) proposed a simple way to choose the threshold in estimating a tail index. In this article, the author first gives an intuitive explanation of the approach in Guillou & Hall (2001; it Journal of Royal Statistical Society B, 63, 293–305) and then proposes an alternative method, which can be extended to other settings like extreme value index estimation and tail dependence function estimation. Further the author proposes to combine this method for selecting a threshold with a bias reduction estimator to improve the performance of the tail index estimation, interval estimation of a tail index, and high quantile estimation. Simulation studies on both point estimation and interval estimation for a tail index show that both selection procedures are comparable and bias reduction estimation with the threshold selected by either method is preferred. The Canadian Journal of Statistics © 2009 Statistical Society of Canada
Cardiac Amyloidosis Treated with an Implantable Cardioverter Defibrillator and Subcutaneous Array Lead System: Report of a Case and Literature Review
Authors: Dhoble Abhijeet , Khasnis Atul , Olomu Adesuwa , Thakur Ranjan
Published: May 2009

Background

Preventing ventricular arrhythmias in patients with cardiac amyloidosis is challenging since the amyloid protein deposition in the myocardium may interfere with the normal cardiac electric excitation. Most of these patients succumb to either progressive congestive heart failure, or sudden cardiac death (SCD). Implantable Cardioverter Defibrillator (ICD) offers a near sure means of preventing SCD.

Hypothesis

Myocardial infiltration with amyloid results in elevated defibrillation threshold (DFT). Intra‐operative strategies may fail to lower DFT during implantation.

Methods

We present a case of a 64‐year‐old female who had cardiac amyloidosis, and was successfully treated with an ICD and a subcutaneous array lead system.

Conclusion

A subcutaneous array lead system is useful in reducing the DFT, and can terminate ventricular tachycardia or fibrillation by allowing more energy delivery and efficient defibrillation. Copyright © 2009 Wiley Periodicals, Inc.
Ascending Aortic Aneurysm by Cardiac CT Angiography
Authors: Pal Raveen , Gopal Ambarish , Budoff Matthew J.
Published: May 2009

Thoracic aortic aneurysm (TAA) is an increasingly frequent and potentially life‐threatening medical diagnosis. TAA is defined as a localized dilatation of the aorta to more than 50% of baseline. Patients are most commonly asymptomatic at the time of diagnosis. Diagnosis is made incidentally on chest radiography or echocardiography. Diagnosis is then confirmed by echocardiography, left ventricular angiography, cardiac computed tomography or cardiac magnetic resonance. Cardiac computed tomography angiography (CTA) is an excellent imaging modality for this purpose as it allows simultaneous analysis of the coronary artery tree, which is useful in determining the most suitable procedure for each patient. Copyright © 2009 Wiley Periodicals, Inc.
A Case of Primary Cardiac Lymphoma Mimicking Acute Myocardial Infarction
Authors: Sankaranarayanan Rajiv , Prasanna MD Krishna
Published: May 2009

We present a case of primary cardiac lymphoma (PCL) that masqueraded as acute myocardial infarction with typical symptoms, electrocardiogram (ECG) changes, and raised troponin T levels. This case throws light on a rare cardiac tumor with varied presentation, underlining the need for a high index of suspicion. Copyright © 2009 Wiley Periodicals, Inc.
Plaque Characteristics of the Coronary Segment Proximal to the Culprit Lesion in Stable and Unstable Patients
Authors: Nakamura Tomohiro , Kubo Norifumi , Funayama Hiroshi , Sugawara Yoshitaka , Ako Junya , Momomura Shin‐ichi
Published: May 2009

Background

Identifying vulnerable plaque is important for preventing an acute coronary event. The present study examined the relationship between the clinical presentation of coronary artery disease and the plaque characteristics of nonculprit segment assessed by virtual histology intravascular ultrasound (VH‐IVUS).

Method

We performed VH‐IVUS analysis on nonculprit segments with < 50% diameter stenosis in 91 patients (48 acute coronary syndrome [ACS] patients, 43 stable angina [SA] patients).

Results

ACS patients showed significantly higher ratio of dense calcium (7.9% ± 1.0% versus 5.0% ± 0.9%, p = 0.03) and necrotic core plaque (13.7% ± 1.1% versus 8.6% ± 1.1%, p = 0.001) compared with SA patients. VH‐IVUS‐derived thin‐cap fibroatheroma (VH‐TCFA) was more frequently observed in ACS patients compared with SA patients (64.6% versus 35.7%, p = 0.006). Among ACS patients, plasma high sensitivity C‐reactive protein (hs‐CRP) levels were significantly higher in patients with VH‐TCFA than in patients without VH‐TCFA (7.9 ± 2.6 mg/l versus 1.6 ± 0.3 mg/l, p = 0.004).

Conclusion

ACS patients presented higher prevalence of VH‐TCFA in nonculprit segment. Presence of VH‐TCFA was associated with an increased level of plasma hs‐CRP in ACS patients. Copyright © 2009 Wiley Periodicals, Inc.
The communication model for real‐time web service in telecom domain
Authors: Bo Cheng , Jie Guo , Junliang Chen , Xiangwu Meng
Published: May 2009

Development of services that span over the Internet and Telecom networks is driving significant efforts towards the integration of services offered by Telecom operators. The telecommunications R&D community also starts adapting and developing similar service delivery platforms to offer a wide range of new value‐added services faster and more cost efficiently inspired by the success of Web service technologies for the development and deployment of IT services. In this paper, we have an analysis for Telecom Web services communication requirements and also propose Telecom Web services communication model considering the specific characteristics as state, asynchronous, event‐driven communications in Telecom domain. We focus on the design and implementation details for real‐time Web service communication model in Telecom domain, and as the framework of communication model for Telecom Web services, the enhanced state machine design and implementation, and the messages dispatching design and implementation for Telecom Web services communication model, and also illustrate the third party end call control scenarios. Finally, we give the conclusion and future essential work. Copyright © 2009 John Wiley & Sons, Ltd.
Characterisation of BaZr0.9Y0.1O3‐δ Prepared by Three Different Synthesis Methods: Study of the Sinterability and the Conductivity
Authors: Duval S. B. C. , Holtappels P. , Vogt U. F. , Stimming U. , Graule T.
Published: May 2009

BaZr0.9Y0.1O3‐δ has been synthesised by three different methods: the solid‐state reaction, the spray pyrolysis and the spray drying. Significantly different apparent lattice parameters (between 0.4192 nm for the sample prepared by the solid‐state reaction method and sintered at 1,500 °C and 0.4206 nm for the sample prepared by the solid‐state reaction method and sintered at 1,720 °C) are observed after calcination and sintering, depending on the synthesis method and the sintering temperature. The bulk conductivity values also vary over several orders of magnitude (–7.2< log σb <–3.6 at 300 °C) depending on the synthesis method and the sintering temperature. These variations of the bulk conductivity and also the activation energy are correlated with variations of the apparent lattice parameter. The influence of the preparation method on the electrical properties is discussed. The grain boundaries are more resistive than the bulk. The variation of the grain boundary conductivity could be correlated to the microstructure in terms of the grain size.
On the Approximation of Transport Phenomena – a Dynamical Systems Approach
Authors: Dellnitz Michael , Froyland Gary , Horenkamp Christian , Padberg Kathrin
Published: May 2009

Transport phenomena are studied in a large variety of dynamical systems with applications ranging from the analysis of fluid flow in the ocean and the predator‐prey interaction in jelly‐fish to the investigation of blood flow in the cardiovascular system. Our approach to analyze transport is based on the methodology of so‐called transfer operators associated with a dynamical system since this is particularly suitable. We describe the approach and illustrate it by two real world applications: the computation of transport for asteroids in the solar system and the approximation of macroscopic structures in the Southern Ocean (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
On the generation of conjugate flanks for arbitrary gear geometries
Authors: Johann A. , Scheurle J.
Published: May 2009

In this paper, we present a novel approach to three‐dimensional mathematical gearing theory. We start from a general formulation of the so called basic law of gear kinematics. Based on that we derive an analytic closed form solution for the generation of conjugate tooth flanks, given a (local) parametric representation for any prescribed flank profile. Also, we study the problem of constructing pairs of tooth flanks that give rise to a prescribed surface of action. Surfaces of action will be represented in an implicit global rather than in a parametric way. To illustrate the general theory, we consider a number of specific examples including the standard involute profile for spur gears as well as a more sophisticated three‐dimensional generalization of that (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Modelling disturbances in early sensory processing in schizophrenia
Authors: Popovych S. , Küpper T. , Müller R. , Brockhaus‐Dumke A.
Published: May 2009

Recent results suggest that disturbances of information processing within the thalamo‐cortical circuit are central in the pathophysiology of schizophrenia. We derive a mathematical model based on phase oscillators to describe the neural activity within the thalamo‐cortical loop and show that the results derived from the corresponding equations coincide with experimental data obtained by EEG measurements. It is an important advantage of the mathematically based approach that information concerning activities in deeply localized brain areas which are not directly accessible to measurements becomes available. The mathematical model describes differences between healthy subjects and patients with schizophrenia by various states of phase locking between different brain areas involved (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Breaks invisible to the DNA damage response machinery accumulate in ATM‐deficient cells
Authors: Martín Marta , Terradas Mariona , Iliakis George , Tusell Laura , Genescà Anna
Published: May 2009

After irradiation, ATM defective cells accumulate unrepaired double strand breaks (DSBs) for several cell divisions. At the chromosome level, unresolved DSBs appear as chromosome breaks that can be efficiently scored by using telomeric and mFISH probes. H2AX is immediately activated by ATM in response to DNA damage and its phosphorylated form, γH2AX, flanks the DSB through several megabases. The γH2AX‐labeling status of broken chromosome ends was analyzed in AT cells to check whether the DNA damage response was accurately taking place in these persistent DSBs. The results show that one quarter of the scored breaks are devoid of γH2AX foci in metaphase spreads from ATM‐deficient cells, and this fraction is significantly higher than in normal cells (χ2 < 0.05). Accumulation of sensor and repair proteins at damaged sites is a key event in the cellular response to DSBs, so MRE11 labeling at broken ends was also analyzed. While all γH2AX foci scored at visible broken ends colocalize with MRE11 foci, all γH2AX‐unlabeled breaks are also devoid of MRE11‐labeling. The present results suggest that a significant subset of the AT long‐lived DSBs may persist as “invisible” DSBs due to deficient detection by the DNA damage repair machinery. Eventually the properly signaled DSBs will be repaired while invisible breaks may indefinitely accumulate; most probably contributing to the AT cells' well known genomic instability. © 2009 Wiley‐Liss, Inc.
Parametric model‐based statistics for possible genotyping errors and sample stratification in sibling‐pair SNP data
Authors: Korostishevsky Michael , Malkin Ida , Spector Tim , Livshits Gregory
Published: May 2009

The detection of genotyping errors, based on apparent Mendelian incompatibilities in a sample of sib‐pairs, is a complicated problem. In the case of a single marker and unknown parental genotypes, all combinations of sib‐pair genotypes are self‐consistent. Moreover, the observed deviation from equilibrium genotype frequencies may result from genotyping errors as well as from the sample's stratification. This in turn, may profoundly affect the results of association and linkage analyses, and therefore an estimation of these factors should be done beforehand. Here we present several parametric models, and using likelihood ratio statistics, we suggest a method of combined analysis of genotyping errors and a sample stratification for randomly ascertained sib‐pair single nucleotide polymorphism (SNP) data. Specifically, we implemented two models of genotyping errors in either heterozygotes or homozygotes, and two models of sample stratification resulting from either the presence of families of different ethnic origin (e.g., a population admixture) or from a different ethnic origin of the parents in the family (e.g., intermarriage). The power of this method was established by Monte Carlo data simulation. The results clearly suggest that the proposed method is most efficient for detecting genotyping errors in heterozygotes, a common error caused by incorrect SNP data interpretation. We also provide an example of its application to real data. Genet. Epidemiol. 34:26–33, 2010. © 2009 Wiley‐Liss, Inc.
Discovering genetic ancestry using spectral graph theory
Authors: Lee Ann B. , Luca Diana , Klei Lambertus , Devlin Bernie , Roeder Kathryn
Published: May 2009

As one approach to uncovering the genetic underpinnings of complex disease, individuals are measured at a large number of genetic variants (usually SNPs) across the genome and these SNP genotypes are assessed for association with disease status. We propose a new statistical method called Spectral‐GEM for the analysis of genome‐wide association studies; the goal of Spectral‐GEM is to quantify the ancestry of the sample from such genotypic data. Ignoring structure due to differential ancestry can lead to an excess of spurious findings and reduce power. Ancestry is commonly estimated using the eigenvectors derived from principal component analysis (PCA). To develop an alternative to PCA we draw on connections between multidimensional scaling and spectral graph theory. Our approach, based on a spectral embedding derived from the normalized Laplacian of a graph, can produce more meaningful delineation of ancestry than by using PCA. Often the results from Spectral‐GEM are straightforward to interpret and therefore useful in association analysis. We illustrate the new algorithm with an analysis of the POPRES data [Nelson et al., 2008]. Genet. Epidemiol. 34:51–59, 2010. © 2009 Wiley‐Liss, Inc.