bluuebunny/crossref_metadata_2025 huggingface dataset:
Gradual morphogenesis of retinal neurons in the peripheral retinal margin of adult monkeys and humans
Authors: Martínez‐Navarrete Gema C. , Angulo Antonia , Martín‐Nieto José , Cuenca Nicolás
Published: October 2008

The adult mammalian retina has for long been considered to lack a neurogenerative capacity. However, retinal stem/progenitor cells, which can originate retinal neurons in vitro, have been recently reported in the ciliary body of adult mammals. Here we explored the possibility of retinal neurogenesis occurring in vivo in adult monkeys and humans. We found the presence of cells expressing molecular markers of neural and retinal progenitors in the nonlaminated retinal margin and ciliary body pars plana of mature primates. By means of immunohistochemistry and electron microscopy we also observed photoreceptors and other retinal cell types in different stages of morphological differentiation along the peripheral retinal margin. These findings allow us to extend to primates the idea of neurogenesis aimed at retinal cell turnover throughout life. J. Comp. Neurol. 511:557–580, 2008. © 2008 Wiley‐Liss, Inc.
Dynamic allocation in a self‐scaling cluster database
Authors: Rabl T. , Pfeffer M. , Kosch H.
Published: October 2008

Database systems have been vital for all forms of data processing for a long time. In recent years, the amount of processed data has been growing dramatically, even in small projects. Nevertheless, database management systems tend to be static in terms of size and performance, which makes scaling a difficult and an expensive task. This is especially an acute problem in dynamic environments such as grid systems.

On the basis of the C‐JDBC project, we developed a cluster database that supports automatic scaling in the number of nodes used. To ensure good load balancing, we distribute the tablespace according to a statistical analysis of the query history. In this paper, we will focus on the allocation algorithm. Copyright © 2008 John Wiley & Sons, Ltd.
Improving Purity and Size Control of Iron‐ and Molybdenum‐Supported Nanoparticles Prepared by OMCVD from their Carbonyl Precursors
Authors: Lamouroux Emmanuel , Corrias Massimiliano , Ressier Laurence , Kihn Yolande , Serp Philippe , Kalck Philippe
Published: October 2008

Communication: OMCVD using zero‐valent metal carbonyl and water vapor is employed to grow Fe and Mo nanoparticles. The introduction of water vapor during deposition enables to limit carbon contamination via surface reactions. The influence of the concentration of hydroxyl groups on the substrate and of the precursor partial pressure on the size of deposited nanoparticles is demonstrated.
PECVD Siloxane and Fluorine‐Based Copolymer Thin Films
Authors: Jiang Hao , Eyink Kurt , Grant John T. , Enlow Jesse , Tullis Scott , Bunning Timothy J.
Published: October 2008

Plasma copolymerization is utilized to fabricate thin photonic films based on hexamethyldisiloxane (HMDSO, C6H18Si2O) and octafluorocyclobutane (OFCB, C4F8). The structure of the plasma copolymerized films is examined by X‐ray photoelectron spectroscopy (XPS) and Fourier transform infrared spectroscopy (FTIR), and the optical properties including refractive index, n, and extinction coefficient, k, are determined by spectroscopic ellipsometry. The refractive indices, which range from 1.38 to 1.54, can be manipulated by adjusting the volume ratio of the two monomers, HMDSO and OFCB, during the polymerization. A nonlinear relationship between the refractive index and extinction coefficient with comonomer feed ratio is observed. A strong initial increase in both n and k as the amount of HMDSO is increased is attributed to significant defluorination of the resultant polymer films coupled with the formation of a C‐C rich crosslinked network. Once the network incorporates substantial amounts of Si‐C and Si‐O bonds, the refractive index starts to decrease slowly due to a lowering of the density. XPS and FTIR results confirm the changes in internal structure consistent with this mechanism.
Tribenzyltin(IV)chloride Thiosemicarbazones: Novel Single Source Precursors for Growth of SnS Thin Films
Authors: Bade Balasaheb P. , Garje Shivram S. , Niwate Yogesh S. , Afzaal Mohammad , O'Brien Paul
Published: October 2008

Tin sulfide (SnS) thin films are deposited using simple tin thiosemicarbazone complexes of the type Bz3SnCl(L) (L = thiosemicarbazones of salicylaldehye and 4‐chlorobenzaldehyde). Thin films are deposited using aerosol‐assisted (AA) CVD in the range 375–475 °C. X‐ray diffraction (XRD) shows the formation of SnS regardless of growth temperature and precursor type. Scanning electron microscope (SEM) images show that the films have wafer‐like morphology, and the growth temperatures do not have a profound effect on morphology.
An Analysis of the Deposition Mechanisms involved during Self‐Limiting Growth of Aluminum Oxide by Pulsed PECVD
Authors: Seman Michael T. , Richards David N. , Rowlette Pieter , Wolden Colin A.
Published: October 2008

Self‐limiting growth of Al2O3 is accomplished using both pulsed plasma‐enhanced (PE) CVD and plasma‐enhanced atomic layer deposition (PEALD). In pulsed PECVD the two reactants (Al(CH3)3/TMA and O2) are supplied continuously, while in PEALD the TMA is delivered in pulses separated by purge steps. For both processes the rate per cycle saturates with ∼200 L of TMA exposure. At 165 °C a rate of 1.37 Å per cycle is obtained using PEALD. For pulsed PECVD the rate scales linearly with the TMA partial pressure, and its extrapolation is in good agreement with PEALD. The results suggest that deposition in pulsed PECVD involves an ALD component which is supplemented by PECVD growth, and that the contribution of the latter may be tuned using the TMA partial pressure. Experiments using patterned wafers support this hypothesis. Conformal coatings are observed within 10:1 aspect ratio trenches using pulsed PECVD; however the deposition rate on the surface of these substrates is greater than within the trench. The ratio between the two corresponds well to the ratio of rates obtained from pulsed PECVD and PEALD on planar substrates. With cycle times <1 s, net rates up to 20 nm min−1 are obtained by pulsed PECVD while retaining high quality and digital control.
An Investigation of Titanium‐Vanadium Nitride Phase Space, Conducted Using Combinatorial Atmospheric Pressure CVD
Authors: Hyett Geoffrey , Green Mark A. , Parkin Ivan P.
Published: October 2008

The technique of combinatorial atmospheric pressure (AP)CVD, a recent addition to the growing number of combinatorial materials methods, is used to form twelve members of the TixV1‐xN alloy series with 0.29 < x < 0.94. This series of compounds has a rock‐salt structure with TiN and VN as the end members. The twelve phases, which have potential use as heat mirror coatings, are all synthesized in a single experiment. The structure and properties of the materials are investigated using powder X‐ray diffraction (XRD) and electron probe microanalysis (EPMA). The optical properties are considered using visible‐IR spectroscopy (IRS), which allows the suitability of the films as solar control coatings to be investigated and optimized as a function of composition.
Thin Polymer Films with High Step Coverage in Microtrenches by Initiated CVD
Authors: Baxamusa Salmaan H. , Gleason Karen K.
Published: October 2008

Initiated (i)CVD is used to deposit thin films of poly(cyclohexylmethacrylate) (pCHMA) in microtrenches of depth 7 µm and widths 1‐5 µm. By changing the fractional saturation of the monomer vapor, step coverage of 0.85 is achieved for the highest aspect ratio trench studied while maintaining a deposition rate of 15 nm min−1. An analytical model for determining the sticking probability of the initiating radical (CH3)3CO· is developed, and is experimentally shown to be a function of the fractional saturation of the monomer vapor. For the conditions studied, the sticking probability is in the range 1.1 × 10−2–5.0 × 10−2. These results suggest that iCVD proceeds via the reaction of a vapor‐phase initiating radical with a surface‐adsorbed monomer.
Parameters influencing derivation of embryonic stem cells from murine embryos
Authors: Batlle‐Morera Laura , Smith Austin , Nichols Jennifer
Published: October 2008

The derivation of ES cells is poorly understood and varies in efficiency between different strains of mice. We have investigated potential differences between embryos of permissive and recalcitrant strains during diapause and ES cell derivation. We found that in diapause embryos of the recalcitrant C57BL/6 and CBA strains, the epiblast failed to expand during the primary explant phase of ES cell derivation, whereas in the permissive 129 strain, it expanded dramatically. Epiblasts from the recalcitrant strains could be expanded by reducing Erk activation. Isolation of 129 epiblasts facilitated very efficient derivation of ES cell lines in serum‐ and feeder‐free conditions, but reduction of Erk activity was required for derivation of ES cells from isolated C57BL/6 or CBA epiblasts. The results suggest that the discrepancy in ES cell derivation efficiency is not attributable merely to variable prodifferentiative effects of the extra‐embryonic lineages but also to an intrinsic variability within the epiblast to maintain pluripotency. genesis 46:758–767, 2008. © 2008 Wiley‐Liss, Inc.
A new Bayesian formulation for Holt's exponential smoothing
Authors: Andrawis Robert R. , Atiya Amir F.
Published: October 2008

In this paper we propose a Bayesian forecasting approach for Holt's additive exponential smoothing method. Starting from the state space formulation, a formula for the forecast is derived and reduced to a two‐dimensional integration that can be computed numerically in a straightforward way. In contrast to much of the work for exponential smoothing, this method produces the forecast density and, in addition, it considers the initial level and initial trend as part of the parameters to be evaluated. Another contribution of this paper is that we have derived a way to reduce the computation of the maximum likelihood parameter estimation procedure to that of evaluating a two‐dimensional grid, rather than applying a five‐variable optimization procedure. Simulation experiments confirm that both proposed methods give favorable performance compared to other approaches. Copyright © 2008 John Wiley & Sons, Ltd.
Simultaneous prediction intervals for ARMA processes with stable innovations
Authors: Nolan John P. , Ravishanker Nalini
Published: October 2008

We describe a method for calculating simultaneous prediction intervals for ARMA times series with heavy‐tailed stable innovations. The spectral measure of the vector of prediction errors is shown to be discrete. Direct computation of high‐dimensional stable probabilities is not feasible, but we show that Monte Carlo estimates of the interval width is practical. Copyright © 2008 John Wiley & Sons, Ltd.
Development of New Models for Geomechanical Characterisation Using Data Mining Techniques
Authors: Miranda Tiago , Correia António Gomes , Ribeiro e Sousa Luís
Published: October 2008

The evaluation of geomechanical parameters for rock masses is one of the issues with largest uncertainty degree. This is mostly true in the preliminary stages of design and in small works where geotechnical information is normally scarce. In these cases, geotechnical data from past projects could help in the definition of design values for the parameters. Data Mining techniques have been successfully used in many fields. They are advanced techniques which allow to analyse large and complex databases like the ones it would be possible to build with geotechnical information. In this context, it was intended to gather a large database of geotechnical data and use these innovative tools to analyse and induce new and useful knowledge. The main goal was to develop new and reliable models to predict geomechanical parameters values mainly when only limited data is available.
The Role of Advanced Constitutive Models in Geotechnical Engineering
Authors: Schweiger Helmut F.
Published: October 2008

Numerical calculations have a long tradition in tunnelling but in recent years numerical methods have become a standard tool for analysing a wide variety of geotechnical problems. This has become feasible because advanced constitutive models are available in commercial software packages and sufficient computer power for performing 3D nonlinear analysis is readily available. In this paper a short history of the development of constitutive models for soils will be given, starting from (non)linear elasticity to strain hardening formulations. Emphasis is put on consequences the use of different models has on the results of boundary value problems rather than on the mathematical description. The significant advances made within the last decade will be obvious. It is pointed out that this overview is directed towards practical applications and does not include models which are predominantly used in research. The merits of using advanced models in practice are discussed.
Ankerung im Untertagebau – Entwicklungen in Theorie und Praxis
Authors: Kainrath‐Reumayer Stefan , Neugebauer Erich , Charette Francois , Plouffe Michel , Galler Robert
Published: October 2008

Die systematische Ankerung des Gebirges stellt ein wesentliches Verfahren zur Stabilisierung unterirdischer Hohlraumbauten dar. Die geschichtliche Entwicklung verschiedener Ankersysteme wird kurz vorgestellt und Unterteilungsmöglichkeiten werden aufgezeigt. Unterschiedliche Ansätze der Systemankerungen in analytischen und numerischen Berechnungen werden mit der diskreten Modellierung des Gesamtssystems in numerischen Berechnungen mit FLAC3D verglichen. Der Einfluss von Systemankerungen auf das Systemverhalten ist von einer Reihe von Randbedingungen abhängig, der Erfolg der Anwendung oftmals von den verwendeten Ankersystemen.

Extreme Spannungszustände im Gebirge stellen hohe Anforderungen an die Methodik der Gebirgsankerung in Untertagebauwerken, die mit den herkömmlichen Ankerungssystemen nur eher unzufriedenstellend zu bewältigen sind. In Abhängigkeit von den Eigenschaften des Gebirges ist unter solch hohen, die Festigkeit des intakten Gebirges meist bereits überschreitenden Spannungszuständen mit großen Verschiebungen, Stabilitätsproblemen sowie Bergschlagphänomenen zu rechnen. Um diesen Anforderungen bestmöglich gerecht zu werden, wird ein neuartiger, energieabsorbierender Ankertyp “Roofex” vorgestellt, der sowohl unter langsam kriechenden, statischen, wie auch abrupten, dynamischen Beanspruchungen einen kontrollierbaren und konstanten Widerstand entlang eines definierten Gleitwegs aufweist.
The Development of the Observational Method
Authors: Schubert Wulf
Published: October 2008

A continuous observation during construction always has been an important element of geotechnical engineering for minimizing risks. The reasons are the uncertainties in the geological and geotechnical models, as well as the limited capability to sufficiently accurately describe the complex ground behaviour. In the early days design of geotechnical structures thus was mainly based on experience. As usual, experience was used to develop mathematical solutions to the problem. To account for the inherent scatter of parameters and uncertainties in the models, the assumptions made during design had and have to be verified or falsified during construction by observations. For safe and economical construction, the design has to be adjusted during construction to the actual conditions. The term “observational method” was first formally introduced by Peck and Terzaghi. The original ideas behind the method have not always been understood or followed. After a brief historical review of the observational method the current status of the method is critically reviewed, and further developments discussed.
BEG Tunnel Fritzens – Druckluftvortrieb mit Unterstützung zweireihiger horizontaler DSV‐Schirme
Authors: Hornich Wolfgang , Geisler Hansjörg
Published: October 2008

Die Unterquerung des Bahnhofes Fritzens in bergmännischer Sonderbauweise unter Druckluftbedingungen im Schutz einer horizontalen DSV‐Sicherung ist einer der schwierigsten und technisch anspruchsvollsten Abschnitte auf der gesamten Neubaustrecke der Unterinntaltrasse. Die besonderen Herausforderungen bei der Ausführung dieser weltweit erstmalig eingesetzten Kombination aus horizontaler DSV‐Vortriebssicherung und Druckluftvortrieb sowie die dabei gesammelten Erfahrungen sind Gegenstand dieses Beitrags.
Baupraktische Erfahrungen eines Vortriebs im Schutz eines umhüllenden Frostkörpers am Beispiel des U‐Bahnhofs Brandenburger Tor, Berlin
Authors: Müller Benno , Bayer Franz
Published: October 2008

In unmittelbarer Nähe zum Brandenburger Tor in Berlin‐Mitte wurde im Kreuzungsbereich Unter den Linden/Wilhelmstraße der U‐Bahnhof Brandenburger Tor überwiegend in bergmännischer Bauweise im Schutz einer Bodenvereisung erbaut. Die Arbeitsgemeinschaft, bestehend aus Hochtief Construction AG, Berlin, und Max Bögl GmbH & Co. KG, München, erhielt hierzu im Jahr 2005 den Auftrag von den Berliner Verkehrsbetrieben. In einem Alternativkonzept zur Ausschreibung wurden erstmals mit Eis gefüllte Mikrotunnel in das thermische und statische System des Frostkörpers eingebunden. Die Rohbauarbeiten wurden im Sommer 2008 abgeschlossen.
Advanced Ground Freezing at the Hallandsås Project, Sweden
Authors: Sturk Robert , Stille Björn
Published: October 2008

An extensive fault zone within the Hallandsås Project Sweden, a railway tunnel project in southwest of Sweden, is subject of an advanced ground freezing operation in order to facilitate TBM excavation through this section. The rock mass within the fault zone consists of a completely decomposed gneiss and amphibolite in combination with 10 to 12 bar ground water pressure. Ground freezing was carried out in 16 horizontally drilled freeze holes with a length of 100 m. Within the 10.6 m diameter final tunnel section a small 5 m diameter pilot tunnel was excavated through the frozen area. The design and execution of the freezing and excavation operations have followed the observational method. This included prediction, monitoring and follow up of all parameters associated with design of frozen ground, such as strength and creep properties, as well as design aspects on the final segmental lining installed by the TBM. By thorough project management and active design it is possible to control the involved processes and achieve a transparent methodology in predicting and executing tunnelling using the freezing method.
Das hochdruckseitige Wasserschloss des Kopswerks II – bauliche Planung, Konzeption und technische Ausführung
Authors: Wegeler Gerd , Gerstner Reinhold
Published: October 2008

Das Pumpspeicherkraftwerk Kops II der Vorarlberger Illwerke AG (Österreich), als Parallelwerk zum bestehenden Kopswerk I, nutzt den vorhandenen Speichersee Kops als Oberwasser‐ und das Ausgleichsbecken Rifa im hinteren Montafon als Unterwasserreservoir. Durch die sehr kurzen Regelzeiten der drei Maschinensätze wird der hochdruckseitige Triebwasserweg, bestehend aus Druckschacht, Wasserschloss und Druckstollen, dynamisch stark beansprucht. Das Zweikammerdifferentialwasserschloss liegt in mehreren durch Glimmerschieferbänder getrennten Bergwasserstockwerken. Aufgrund der geologischen Verhältnisse, der Wasserschlossgeometrie und der stark schwankenden Innendruckverhältnisse wurden unterschiedliche Auskleidungsarten verwendet. In der Oberen Kammer konnte aufgrund des geringen Innendrucks eine mit Kontaktinjektionen gebettete Betonschale eingebaut werden, im Wasserschlosssteigschacht wurde eine vorgespannte, größtenteils unbewehrte Betonauskleidung verwendet. In der Unteren Kammer wurden aus verschiedenen bautechnischen Gründen sowohl Panzerungsbereiche als auch durchgehend bewehrte, mit Injektionen vorgespannte Betonauskleidungsstrecken geplant und ausgeführt.
Kopswerk II – Geologie und Felsmechanik bei Erkundung, Planung und Bauausführung der Maschinenkaverne
Authors: Netzer Elmar , Gerstner Reinhold
Published: October 2008

Die Maschinenkaverne des Kopswerks II zählt zu den weltweit größten vergleichbaren Kavernen. Die Vorerkundungen, die geologischen Voraussetzungen und die in baugeologischer und felsmechanischer Hinsicht wesentlichen Aspekte des Kavernenausbruchs werden beschrieben. Die Erfassung der Gebirgseigenschaften, insbesondere des Trennflächengefüges, und deren richtige Vereinfachung für die felsmechanischen Berechnungen waren Voraussetzung für die Entwicklung des Ausbruchs‐ und Sicherungskonzepts. Die zutreffende Prognose der Verformungen war Bedingung für den rechtzeitigen Einbau der Maschinensätze.
BEAM – Geoelectrical Ahead Monitoring for TBM‐Drives
Authors: Kaus Arnim , Boening Wolf
Published: October 2008

BEAM is a non‐intrusive focused‐electrical induced polarisation ground prediction technique, permanently operating while TBM tunnelling. Main components of the survey system are the measuring unit placed in the TBM operator cabin and special adapted excavation tools which are used as electrodes. The unit is connected to the guidance system and receives the boring signal which allows fully automatic data acquisition and visualisation in real‐time on an integrated monitor. Communication facilities transfer the forecast results to every accredited computer world wide simultaneously. Based on the measuring data the percentage frequency effect PFE and the resistivity R, an advanced evaluation software is established for geoelectrical‐geological/hydrogeological classification and interpretation. Selected case studies from international TBM projects are outlined with prediction results of different kinds of exploration targets and geological situations. Since 2000 the geophysical probing system is fulfilling the practical demands under the rough and various conditions of TBM tunnelling work by indicating reliable results in hard rock as well as in soft ground.
Advanced Observation Techniques for Sophisticated Shallow Tunnel Projects – Experience Gained Using Innovative Monitoring Methods at the Lainzer Tunnel LT31
Authors: Moritz Bernd , Matt Robert , Graf Franz , Brandtner Markus
Published: October 2008

The article presents experiences gained during construction of the approximately 3 km long urban Lainzer Tunnel (LT31), driven with side‐wall galleries under shallow overburden. The structure's safety is assessed mainly on the basis of 3D deformation analyses, comparison of predicted and observed system behaviour, evaluation of shotcrete stress, and online monitoring of surface settlements. Displacements of the tunnel face, correlating with pre‐face surface settlements, are monitored by an innovative, fully automatic face monitoring system (OBM). A correlation between volume loss (surface) and volume increase (face) could be established. A test field comparing fibreglass anchors (GRP) with IBO face bolts revealed – contrary to expectations – no appreciable reduction of surface settlement due to GRP anchors. However, temporary inverts constructed in the side wall galleries in combination with IBO face bolts support turned out to be effective in reducing horizontal convergence and resulting settlements of the ground surface in a sensitive residential area.
Analysis of Tunnel Displacements for the Geotechnical Short Term Prediction
Authors: Großauer Karl , Schubert Wulf
Published: October 2008

Measurement of displacements in tunnels is primarily used for the assessment of the stabilization process and the verification of the system behaviour. In addition the displacement data can be used for the prediction of changing ground conditions ahead of the face. For this purpose, the evaluation of displacement vector orientation turned out to be the most appropriate method. Several authors showed the influence of the excavation on the stress and displacement field when tunnelling through zones of different stiffness. One of the main findings was that the displacement vector orientation significantly changes when the excavation approaches ground with different deformability. Hence, it was concluded that the development of the spatial orientation of the displacement vector can be used for the prediction of the ground conditions ahead of the face. The main results of the investigations performed are summarized in this paper. The evaluation of data from three different case histories is shown in order to encourage the use of advanced displacement data evaluation.
HPP Glendoe – Rock Mechanical Aspects for Large Span Underground Powerhouse
Authors: Fellner Dieter , Hobson David
Published: October 2008

The Glendoe scheme, presently under construction near Fort Augustus, near Inverness, by Scottish and Southern Energy (SSE), will be the first major conventional hydropower scheme to be constructed in the U.K. for the last fifty years and will generate up to 100 MW of electricity. The project will be the most efficient in the U.K. in terms of water to power production. The net head is 605 m, which is the highest head of any UK hydro scheme. The contractor executing the construction works, including the tunnels, underground powerhouse and dam, is the Hochtief Glendoe JV – led by Hochtief. Poyry Energy Ltd is the contractor's designer. Jacobs is advising the client.

After a short general description of the project, this contribution focuses on various rock mechanical design issues for the cavern powerhouse (PH). Located around 250 m below ground level it will incorporate a single 100 MW Pelton turbine. The size of the cavern excavated is (L x W x H) 47 m x 20 m x 33 m. Powerhouse and transformer caverns are designed as intersecting. Layout, shape and rock support were designed to optimize overall costs. Powerhouse detailed design commenced in June 2006, excavation commenced in January and finished in April 2007 ahead of schedule.
Improved Design Method for Pre‐stressed Water Tunnels
Authors: Radončić Nedim , Großauer Karl , Schubert Wulf , Gober Hans‐Jörg , Heigerth Günther
Published: October 2008

The final design of the pumped‐storage project Feldsee features a complex lining and pre‐stress grouting concept, rendering the method presented by Seeber insufficient for an accurate determination of the system behaviour in all stages of construction and operation. A calculation procedure based on the matrix stiffness method has been implemented, allowing incorporation of multistage pre‐stressing injections at different locations of a lining being composed of several layers with different mechanical properties. Based on the design obtained by applying the above method, another question of maximum allowable non‐symmetric displacement of the pre‐cast concrete segment arose. A parametric study has been used to determine the boundaries of asymmetric displacements throughout the pre‐stressing procedure, allowing establishment of threshold values for the monitoring conducted during the pre‐stressing injections.
A multiple splitting approach to linkage analysis in large pedigrees identifies a linkage to asthma on chromosome 12
Authors: Bellenguez Céline , Ober Carole , Bourgain Catherine
Published: October 2008

Large genealogies are potentially very informative for linkage analysis. However, the software available for exact non‐parametric multipoint linkage analysis is limited with respect to the complexity of the families it can handle. A solution is to split the large pedigrees into sub‐families meeting complexity constraints. Different methods have been proposed to “best” split large genealogies. Here, we propose a new procedure in which linkage is performed on several carefully chosen sub‐pedigree sets from the genealogy instead of using just a single sub‐pedigree set. Our multiple splitting procedure capitalizes on the sensitivity of linkage results to family structure and has been designed to control computational feasibility and global type I error. We describe and apply this procedure to the extreme case of the highly complex Hutterite pedigree and use it to perform a genome‐wide linkage analysis on asthma. The detection of a genome‐wide significant linkage for asthma on chromosome 12q21 illustrates the potential of this multiple splitting approach. Genet. Epidemiol. 2009. © 2008 Wiley‐Liss, Inc.
More powerful haplotype sharing by accounting for the mode of inheritance
Authors: Ziegler Andreas , Ewhida Adel , Brendel Michael , Kleensang André
Published: October 2008

The concept of haplotype sharing (HS) has received considerable attention recently, and several haplotype association methods have been proposed. Here, we extend the work of Beckmann and colleagues [2005 Hum. Hered. 59:67–78] who derived an HS statistic (BHS) as special case of Mantel's space‐time clustering approach. The Mantel‐type HS statistic correlates genetic similarity with phenotypic similarity across pairs of individuals. While phenotypic similarity is measured as the mean‐corrected cross product of phenotypes, we propose to incorporate information of the underlying genetic model in the measurement of the genetic similarity. Specifically, for the recessive and dominant modes of inheritance we suggest the use of the minimum and maximum of shared length of haplotypes around a marker locus for pairs of individuals. If the underlying genetic model is unknown, we propose a model‐free HS Mantel statistic using the max‐test approach. We compare our novel HS statistics to BHS using simulated case‐control data and illustrate its use by re‐analyzing data from a candidate region of chromosome 18q from the Rheumatoid Arthritis (RA) Consortium. We demonstrate that our approach is point‐wise valid and superior to BHS. In the re‐analysis of the RA data, we identified three regions with point‐wise P‐values<0.005 containing six known genes (PMIP1, MC4R, PIGN, KIAA1468, TNFRSF11A and ZCCHC2) which might be worth follow‐up. Genet. Epidemiol. 2009. © 2008 Wiley‐Liss, Inc.
What cognitive functions are associated with passive suicidal ideation? Findings from a national sample of community dwelling Israelis
Authors: Ayalon Liat , Litwin Howard
Published: October 2008

Purpose

To identify the specific cognitive domains associated with passive suicidal ideation (e.g. thoughts of being better off dead).

Methods

A cross sectional, national based study of 1,712 individuals over the age of 50. Outcome measure, passive suicidal ideation, was evaluated by the question, ‘in the past month, have you felt that you would rather be dead?’, taken from the Euro‐D. Cognitive domains assessed were time orientation, verbal learning, verbal recall, word fluency, and arithmetic.

Results

After adjusting for demographic and clinical information, those reporting passive suicidal ideation were significantly more likely to have impaired performance on the time orientation task. None of the other cognitive domains were associated with passive suicidal ideation.

Conclusions

Clinicians working with older adults need to be aware not only of demographic and clinical information, but also of cognitive functioning and more specifically, time orientation, as a potential determinant of passive suicidal ideation. Possibly, cognitive domains that are less affected by education and prior learning (e.g. time orientation) have a unique association with passive suicidal ideation. Copyright © 2008 John Wiley & Sons, Ltd.
Investigation of the colorectal cancer susceptibility region on chromosome 8q24.21 in a large German case‐control sample
Authors: Schafmayer Clemens , Buch Stephan , Völzke Henry , von Schönfels Witigo , Egberts Jan Hendrik , Schniewind Bodo , Brosch Mario , Ruether Andreas , Franke Andre , Mathiak Micaela , Sipos Bence , Henopp Tobias , Catalcali Jasmin , Hellmig Stephan , ElSharawy Abdou , Katalinic Alexander , Lerch Markus M. , John Ulrich , Fölsch Ulrich R. , Fändrich Fred , Kalthoff Holger , Schreiber Stefan , Krawczak Michael , Tepel Jürgen , Hampe Jochen
Published: October 2008

Human chromosome 8q24.21 has been implicated as a susceptibility region for colorectal cancer (CRC) as a result of genome‐wide association and candidate gene studies. To assess the impact of molecular variants at 8q24.21 upon the CRC risk of German individuals and to refine the disease‐associated region, a total of 2,713 patients with operated CRC (median age at diagnosis: 63 years) were compared with 2,718 sex‐matched control individuals (median age at inclusion: 65 years). Information on microsatellite instability in tumors was available for 901 patients. Association analysis of SNPs rs10505477 and rs6983267 yielded allelic p‐values of 1.42 × 10−7 and 2.57 × 10−7, respectively. For both polymorphisms, the odds ratio was estimated to be 1.50 (95% CI: 1.29–1.75) under a recessive disease model. The strongest candidate interval, outside of which significance dropped by more than 4 orders of magnitude, was delineated by SNPs rs10505477 and rs7014346 and comprised 17 kb. In a subgroup analysis, the disease association was found to be more pronounced in MSI‐stable tumors (odds ratio: 1.71). Our study confirms the role of genetic variation at 8q24.21 as a risk factor for CRC and localizes the corresponding susceptibility gene to a 17 kb candidate region. © 2008 Wiley‐Liss, Inc.
Chemotherapy enhances vaccine‐induced antitumor immunity in melanoma patients
Authors: Nisticò Paola , Capone Imerio , Palermo Belinda , Del Bello Duilia , Ferraresi Virginia , Moschella Federica , Aricò Eleonora , Valentini Mara , Bracci Laura , Cognetti Francesco , Ciccarese Mariangela , Vercillo Giuseppe , Roselli Mario , Fossile Emanuela , Tosti Maria Elena , Wang Ena , Marincola Francesco , Imberti Luisa , Catricalà Caterina , Natali Pier Giorgio , Belardelli Filippo , Proietti Enrico
Published: October 2008

Combination of chemotherapy with cancer vaccines is currently regarded as a potentially valuable therapeutic approach for the treatment of some metastatic tumors, but optimal modalities remain unknown. We designed a phase I/II pilot study for evaluating the effects of dacarbazine (DTIC) on the immune response in HLA‐A2+ disease‐free melanoma patients who received anticancer vaccination 1 day following chemotherapy (800 mg/mq i.v.). The vaccine, consisting of a combination of HLA‐A2 restricted melanoma antigen A (Melan‐A/MART‐1) and gp100 analog peptides (250 μg each, i.d.), was administered in combination or not with DTIC to 2 patient groups. The combined treatment is nontoxic. The comparative immune monitoring demonstrates that patients receiving DTIC 1 day before the vaccination have a significantly improved long‐lasting memory CD8+ T cell response. Of relevance, these CD8+ T cells recognize and lyse HLA‐A2+/Melan‐A+ tumor cell lines. Global transcriptional analysis of peripheral blood mononuclear cells (PBMC) revealed a DTIC‐induced activation of genes involved in cytokine production, leukocyte activation, immune response and cell motility that can favorably condition tumor antigen‐specific CD8+ T cell responses. This study represents a proof in humans of a chemotherapy‐induced enhancement of CD8+ memory T cell response to cancer vaccines, which opens new opportunities to design novel effective combined therapies improving cancer vaccination effectiveness. © 2008 Wiley‐Liss, Inc.
Plasma 25‐hydroxyvitamin D and premenopausal breast cancer risk in a German case‐control study
Authors: Abbas Sascha , Chang‐Claude Jenny , Linseisen Jakob
Published: October 2008

Laboratory and epidemiological data have linked vitamin D to breast cancer prevention. Beside dietary intake, endogenous production of vitamin D substantially contributes to a subject's vitamin D status. Most studies, however, have assessed dietary intake only. Although differential effects of vitamin D on premenopausal and postmenopausal breast cancer have been discussed, this is the first study to investigate the association of plasma 25‐hydroxyvitamin D [25(OH)D], as indicator of the overall vitamin D status, with breast cancer risk with restriction to premenopausal women only. We used data of a population‐based case‐control study comprising 289 cases and 595 matched controls. Information on sociodemographic and breast cancer risk factors was collected by questionnaire and plasma 25(OH)D was measured by enzyme immunoassay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. We observed a significant inverse association between breast cancer risk and plasma 25(OH)D concentrations. Compared with the lowest category (<30 nmol/L), the ORs (95% CI) for the upper categories (30–45, 45–60, ≥60 nmol/L) were 0.68 (0.43–1.07), 0.59 (0.37–0.94) and 0.45 (0.29–0.70), respectively (ptrend = 0.0006). The association was shown to be nonlinear (pnonlinearity = 0.06) in fractional polynomial analysis with a stronger effect in women at low plasma 25(OH)D levels, providing some evidence of a threshold effect (at circa 50 nmol/L). The association was stronger in progesterone receptor negative tumors, with suggestive evidence of effect heterogeneity (pheterogeneity = 0.05, case‐only model). Our findings support a protective effect of vitamin D for premenopausal breast cancer. © 2008 Wiley‐Liss, Inc.
Intramuscular lipid metabolism, insulin action, and obesity
Authors: Consitt Leslie A. , Bell Jill A. , Houmard Joseph A.
Published: October 2008

With the increasing prevalence of obesity, research has focused on the molecular mechanism(s) linking obesity and skeletal muscle insulin resistance. Metabolic alterations within muscle, such as changes in the cellular location of fatty acid transporter proteins, decreased mitochondrial enzyme activity, and defects in mitochondrial morphology, likely contribute to obesity and insulin resistance. These defects are thought to play a role in the reduced skeletal muscle fatty acid oxidation and increased intramuscular lipid (IMCL) accumulation that is apparent with obesity and other insulin‐resistant states such as type 2 diabetes. Intramuscular triacylglycerol does not appear to be a ubiquitous marker of insulin resistance, although specific IMCL intermediates such as long‐chain fatty acyl‐CoAs, ceramide, and diacylglycerol may inhibit insulin signal transduction. In this review, we will briefly summarize the defects in skeletal muscle lipid metabolism associated with obesity, and discuss the proposed mechanisms by which these defects may contribute to insulin resistance. © 2008 IUBMB IUBMB Life, 61(1): 47–55, 2009
Fluorocarbon chain end‐capped poly(carbonate urethane)s as biomaterials: Blood compatibility and chemical stability assessments
Authors: Xie Xingyi , Wang Ruifang , Li Jiehua , Luo Liang , Wen Da , Zhong Yinping , Zhao Changsheng
Published: October 2008

Previous work has shown the synthesis of fluorocarbon chain (CF3(CF2)6CH2O‐) end‐capped poly(carbonate urethane)s (FPCUs) and confirmed the presence of a novel bilayered surface structure in FPCUs, that is, the top fluorocarbon and subsurface hard segment layers (Xie et al., J Biomed Mater Res Part A 2008; 84:30–43). In this work, the effects of such surface structure on blood compatibility were investigated using hemolytic test and platelet adhesion analysis. The chemical stability of the polymers was also determined by Zhao's glass wool‐H2O2/CoCl2 test and phosphate‐buffered saline (PBS, pH = 3.1–3.3) treatment. One of the FPCUs, FPCU‐A, and two control materials, a poly(ether urethane) (PEU) and a poly(carbonate urethane) (PCU), were investigated. No significant difference in hemolytic indices was observed among the three materials, whereas the adherent density and deformation of platelets were much lower on FPCU‐A compared with on PCU and PEU. Severe surface cracking and surface buckling developed in prestressed PEU and PCU films after H2O2/CoCl2 treatment, respectively, whereas smooth surface was observed for the FPCU‐A. PBS incubation resulted in parallel ridge‐like morphology in PCU whereas PEU and FPCU‐A retained their smooth surfaces. Under relatively high stress conditions, all the materials developed well‐oriented strip‐like surface patterns. Results from ATR‐FTIR spectra revealed a surface oxidation mechanism as described in literature. However, observations of universal decrease of molecular weights under stress conditions further suggested the presence of another bulk stress oxidation mechanism. Regardless the degradation mechanisms involved, the unique bilayered surface structure really improved the blood compatibility and chemical stability of FPCU‐A, indicating that further in vivo investigations are worthwhile. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Finite element analysis of the influence of the offset placement of an implant‐supported prosthesis on bone stress distribution
Authors: Anitua E. , Orive G.
Published: October 2008

The aim of this study was to evaluate the influence of the straight alignment versus distal offset placement of an implant‐supported prosthesis (using implants with different diameters: 4 mm, 4.5 mm, and 5 mm) on bone stress distribution. 3D finite element models of a straight configuration and different offset configurations of the implant‐supported prosthesis (until 2.4 mm distal offset) were evaluated for the three implant diameters. A mesial load of 200 N and a distal load of 230 N were applied to the prosthesis. Results showed that implant offset provokes an opposite effect in bone stress depending on the exposed mesial or distal force. The former increases stress whereas the latter induces a dissipation of bone stress proportional to the offset. From these two forces, an optimal offset is created in which maximum bone stress is reduced in the range of 7–8% compared with the straight configuration. Increasing implant diameter from 4 to 5 mm decreased bone stress in 30% for all configurations. These data suggests that offset implant placement apart from enabling an optimal aesthetic restoration, reduces bone stress compared with the straight configuration. The use of wider implants permitted the reduction of the maximum bone stress in all the simulated configurations © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Studies on the condensation of depolymerized chitosans with DNA for preparing chitosan‐DNA nanoparticles for gene delivery applications
Authors: Morris Viola B. , Neethu S. , Abraham T. E. , Pillai C. K. S. , Sharma Chandra P.
Published: October 2008

High molecular weight chitosan (CS) was depolymerized by oxidative degradation with NaNO2 at room temperature to get 11 samples of CS derivatives of varying molecular weights with a view to assessing their effective molecular weight range for gene delivery applications. Viscosity studies indicated that the molecular weight of the depolymerized CS was proportional to the CS/NaNO2 ratio. The condensation behavior of DNA/CS complexes at various charge ratios was studied using UV spectroscopy, FTIR, CD, SEM, and AFM. The results indicated that CSs having very low molecular weights and high charge density exhibited strong binding affinity to DNA compared to high molecular weight CSs. However, the very low molecular weight (1.9–7.7 kDa) CSs were found to form aggregates easily even at very low charge ratios. On the other hand, CSs having medium molecular weight (49–51 kDa) and high degree of deacetylation (DD) gave stable uniform‐sized nanoparticles. Biological studies carried out with the spherical nano‐sized polyplexes formed between CS of 50 kDa (DD of 94%) and pEGFP plasmid DNA at N/P ratio of 5.0 showed excellent gene transfection efficiency at pH 6.5 in HeLa cells without cytotoxicity indicating their potential as genedelivery carriers. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Selective Laser Melting: A regular unit cell approach for the manufacture of porous, titanium, bone in‐growth constructs, suitable for orthopedic applications
Authors: Mullen Lewis , Stamp Robin C. , Brooks Wesley K. , Jones Eric , Sutcliffe Christopher J.
Published: October 2008

In this study, a novel porous titanium structure for the purpose of bone in‐growth has been designed, manufactured and evaluated. The structure was produced by Selective Laser Melting (SLM); a rapid manufacturing process capable of producing highly intricate, functionally graded parts. The technique described utilizes an approach based on a defined regular unit cell to design and produce structures with a large range of both physical and mechanical properties. These properties can be tailored to suit specific requirements; in particular, functionally graded structures with bone in‐growth surfaces exhibiting properties comparable to those of human bone have been manufactured. The structures were manufactured and characterized by unit cell size, strand diameter, porosity, and compression strength. They exhibited a porosity (10–95%) dependant compression strength (0.5–350 Mpa) comparable to the typical naturally occurring range. It is also demonstrated that optimized structures have been produced that possesses ideal qualities for bone in‐growth applications and that these structures can be applied in the production of orthopedic devices. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Micro/nanostructural porous surface on titanium and bioactivity
Authors: Gao Ling , Feng Bo , Wang Jianxin , Lu Xiong , Liu Dali , Qu Shuxin , Weng Jie
Published: October 2008

Porous surfaces can improve both early fixation and long‐term stabilization of implants by contrast with smooth surfaces. In this study, a microporous surface on titanium was prepared by acid etching and the size of micropores ranged from 1 to 60 μm. The micro/nanostructural porous layer on this microporous surface was obtained by acid etching and anodization. In this micro/nanostructural porous layer, the diameter of nanotubes was about 100 nm. After heat treatment at 450°C for 6 h, the oxides on micro/nanostructural surface transformed into anatase crystals and the grain size of anatase was about 20 nm. The bioactivity of samples was investigated respectively in simulated body fluid and a bovine serum albumin (BSA) solution. The information of specimen surfaces was detected using scanning electron microscope, X‐ray diffractometer, and attenuated total reflection Fourier transform infrared spectroscope. The results showed that the sample with micro/nanostructural porous surface and anatase had excellent bioactivity under nonpretreatment. It had more hydroxyapatite (HA) formation and faster BSA adsorption than other samples under the same conditions. Besides, the HA coating on the micro/nanostructure surface had larger range thickness, no microcrack, and no separated interface from substrate. Therefore, this micro/nanostructural porous surface may be an ideal modification layer for preparing bioactive implants. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009
Sputtered iridium oxide films for neural stimulation electrodes
Authors: Cogan Stuart F. , Ehrlich Julia , Plante Timothy D. , Smirnov Anton , Shire Douglas B. , Gingerich Marcus , Rizzo Joseph F.
Published: October 2008

Sputtered iridium oxide films (SIROFs) deposited by DC reactive sputtering from an iridium metal target have been characterized in vitro for their potential as neural recording and stimulation electrodes. SIROFs were deposited over gold metallization on flexible multielectrode arrays fabricated on thin (15 μm) polyimide substrates. SIROF thickness and electrode areas of 200–1300 nm and 1960–125,600 μm2, respectively, were investigated. The charge‐injection capacities of the SIROFs were evaluated in an inorganic interstitial fluid model in response to charge‐balanced, cathodal‐first current pulses. Charge injection capacities were measured as a function of cathodal pulse width (0.2–1 ms) and potential bias in the interpulse period (0.0 to 0.7 V vs. Ag|AgCl). Depending on the pulse parameters and electrode area, charge‐injection capacities ranged from 1–9 mC/cm2, comparable with activated iridium oxide films (AIROFs) pulsed under similar conditions. Other parameters relevant to the use of SIROF on nerve electrodes, including the thickness dependence of impedance (0.05–105 Hz) and the current necessary to maintain a bias in the interpulse region were also determined. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009