bluuebunny/crossref_metadata_2025 huggingface dataset:
New approaches to the treatment of human herpesvirus 8‐associated disease
Authors: Casper Corey
Published: July 2008

Human herpesvirus 8 (HHV‐8, also known as Kaposi sarcoma‐associated herpesvirus or KSHV) is the etiologic agent of Kaposi sarcoma (KS) and primary effusion lymphoma (PEL), as well as many cases of Castleman disease. Despite significant advances in understanding the biology and natural history of these diseases, current treatment options have important limitations, and strategies to prevent their development in high‐risk individuals are lacking. This article reviews the scope of HHV‐8‐associated disease, as well as the efficacy of current treatment options. Finally, novel approaches to treatment and prevention are described, including antiviral agents, targeted molecular therapy and a combination of these modalities. Copyright © 2008 John Wiley & Sons, Ltd.
The enigma of yellow fever in East Africa
Authors: Ellis Brett R. , Barrett Alan D. T.
Published: July 2008

Despite a safe and effective vaccine, there are approximately 200 000 cases, including 30 000 deaths, due to yellow fever virus (YFV) each year, of which 90% are in Africa. The natural history of YFV has been well described, especially in West Africa, but in East Africa yellow fever (YF) remains characterised by unpredictable focal periodicity and a precarious potential for large epidemics. Recent outbreaks of YF in Kenya (1992–1993) and Sudan (2003 and 2005) are important because each of these outbreaks have involved the re‐emergence of a YFV genotype (East Africa) that remained undetected for nearly 40 years and was previously unconfirmed in a clinically apparent outbreak. In addition, unlike West Africa and South America, YF has yet to emerge in urban areas of East Africa and be vectored by Aedes (Stegomyia) aegypti. This is a significant public health concern in a region where the majority of the population remains unvaccinated. This review describes historical findings, highlights a number of disease indicators, and provides clarification regarding the natural history, recent emergence and future risk of YF in East Africa. Copyright © 2008 John Wiley & Sons, Ltd.
Personalized satellite‐based audio and multimedia services for vehicular terminals
Authors: Berioli Matteo , Scalise Sandro , Klinkenberg Frank , Midthassel Rolv , Loeillet Christophe
Published: July 2008

This paper presents the personalized satellite radio, a novel satellite‐based radio concept, capable of providing radio services to vehicular terminals. This paper describes the technical solution proposed, which overcomes the classical streaming approach used for traditional radio. The main concept behind it is that individual audio and multimedia files are broadcast to the mobile users instead of transmitting a number of continuous streams. The received files are stored in a large cache located in the receiver of each mobile terminal and are sequentially played to generate a service similar to traditional radio/entertainment programmes. The resulting file‐based radio approach makes, in particular, use of higher‐layer coding at the transport layer and smart techniques to build up an audible programme with no interruptions and full audio quality based on the available files. This paper also presents the results of extensive trials that were conducted with a system prototype developed in the framework of an European Space Agency funded project. Copyright © 2008 John Wiley & Sons, Ltd.
Bayesian Markov switching models for the early detection of influenza epidemics
Authors: Martínez‐Beneito Miguel A. , Conesa David , López‐Quílez Antonio , López‐Maside Aurora
Published: July 2008

The early detection of outbreaks of diseases is one of the most challenging objectives of epidemiological surveillance systems. In this paper, a Markov switching model is introduced to determine the epidemic and non‐epidemic periods from influenza surveillance data: the process of differenced incidence rates is modelled either with a first‐order autoregressive process or with a Gaussian white‐noise process depending on whether the system is in an epidemic or in a non‐epidemic phase. The transition between phases of the disease is modelled as a Markovian process. Bayesian inference is carried out on the former model to detect influenza epidemics at the very moment of their onset. Moreover, the proposal provides the probability of being in an epidemic state at any given moment. In order to validate the methodology, a comparison of its performance with other alternatives has been made using influenza illness data obtained from the Sanitary Sentinel Network of the Comunitat Valenciana, one of the 17 autonomous regions in Spain. Copyright © 2008 John Wiley & Sons, Ltd.
Analysis of familial aggregation studies with complex ascertainment schemes
Authors: Matthews Abigail G. , Finkelstein Dianne M. , Betensky Rebecca A.
Published: July 2008

Familial aggregation studies are a common first step in the identification of genetic determinants of disease. If aggregation is found, more refined genetic studies may be undertaken. Complex ascertainment schemes are frequently employed to ensure that the sample contains a sufficient number of families with multiple affected members, as required to detect aggregation. For example, an eligibility criterion for a family might be that both the mother and daughter have disease. Adjustments must be made for ascertainment to avoid bias. We propose adjusting for complex ascertainment schemes through a joint model for the outcomes of disease and ascertainment. This approach improves upon previous simplifying assumptions regarding the ascertainment process. Copyright © 2008 John Wiley & Sons, Ltd.
Variance identification and efficiency analysis in randomized experiments under the matched‐pair design
Authors: Imai Kosuke
Published: July 2008

In his 1923 landmark article, Neyman introduced randomization‐based inference to estimate average treatment effects from experiments under the completely randomized design. Under this framework, Neyman considered the statistical estimation of the sample average treatment effect and derived the variance of the standard estimator using the treatment assignment mechanism as the sole basis of inference. In this paper, I extend Neyman's analysis to randomized experiments under the matched‐pair design where experimental units are paired based on their pre‐treatment characteristics and the randomization of treatment is subsequently conducted within each matched pair. I study the variance identification for the standard estimator of average treatment effects and analyze the relative efficiency of the matched‐pair design over the completely randomized design. I also show how to empirically evaluate the relative efficiency of the two designs using experimental data obtained under the matched‐pair design. My randomization‐based analysis differs from previous studies in that it avoids modeling and other assumptions as much as possible. Finally, the analytical results are illustrated with numerical and empirical examples. Copyright © 2008 John Wiley & Sons, Ltd.
Compatible simultaneous lower confidence bounds for the Holm procedure and other Bonferroni‐based closed tests
Authors: Strassburger Klaus , Bretz Frank
Published: July 2008

We consider the problem of simultaneously testing multiple one‐sided null hypotheses. Single‐step procedures, such as the Bonferroni test, are characterized by the fact that the rejection or non‐rejection of a null hypothesis does not take the decision for any other hypothesis into account. For stepwise test procedures, such as the Holm procedure, the rejection or non‐rejection of a null hypothesis may depend on the decision of other hypotheses. It is well known that stepwise test procedures are by construction more powerful than their single‐step counterparts. This power advantage, however, comes only at the cost of increased difficulties in constructing compatible simultaneous confidence intervals for the parameters of interest. For example, such simultaneous confidence intervals are easily obtained for the Bonferroni method, but surprisingly hard to derive for the Holm procedure. In this paper, we discuss the inherent problems and show that ad hoc solutions used in practice typically do not control the pre‐specified simultaneous confidence level. Instead, we derive simultaneous confidence intervals that are compatible with a certain class of closed test procedures using weighted Bonferroni tests for each intersection hypothesis. The class of multiple test procedures covered in this paper includes gatekeeping procedures based on Bonferroni adjustments, fixed sequence procedures, the simple weighted or unweighted Bonferroni procedure by Holm and the fallback procedure. We illustrate the results with a numerical example. Copyright © 2008 John Wiley & Sons, Ltd.
Analysis of longitudinal data to evaluate a policy change
Authors: French Benjamin , Heagerty Patrick J.
Published: July 2008

Longitudinal data analysis methods are powerful tools for exploring scientific questions regarding change and are well suited to evaluate the impact of a new policy. However, there are challenging aspects of policy change data that require consideration, such as defining comparison groups, separating the effect of time from that of the policy, and accounting for heterogeneity in the policy effect. We compare currently available methods to evaluate a policy change and illustrate issues specific to a policy change analysis via a case study of laws that eliminate gun‐use restrictions (shall‐issue laws) and firearm‐related homicide. We obtain homicide rate ratios estimating the effect of enacting a shall‐issue law, which vary between 0.903 and 1.101. We conclude that in a policy change analysis it is essential to select a mean model that most accurately characterizes the anticipated effect of the policy intervention, thoroughly model temporal trends, and select methods that accommodate unit‐specific policy effects. We also conclude that several longitudinal data analysis methods are useful to evaluate a policy change, but not all may be appropriate in certain contexts. Analysts must carefully decide which methods are appropriate for their application and must be aware of the differences between methods to select a procedure that generates valid inference. Copyright © 2008 John Wiley & Sons, Ltd.
Multi‐state analysis of cognitive ability data: A piecewise‐constant model and a Weibull model
Authors: van den Hout Ardo , Matthews Fiona E.
Published: July 2008

Longitudinal data can be used to estimate transition intensities between healthy and unhealthy states prior to death. When health is defined with respect to cognitive ability during old age, the trajectory of performance is either static or downward. An illness–death model is presented where the intensity of a transition is allowed to change over time by using a piecewise‐constant model or by using a Weibull model. Observed improvement of cognitive ability is modelled as misclassification. The methodology is extended to estimate life expectancy with and without cognitive impairment. The measurement of cognitive ability is important as it is an important predictor of future need for care. The models can help to understand how cognitive decline develops over time and which factors play a role. The methods are illustrated using data from the Medical Research Council Cognitive Function and Ageing Study in the U.K. (1991–2005). Copyright © 2008 John Wiley & Sons, Ltd.
Comparisons between ITT and treatment emergent adverse event analyses
Authors: Quan Hui , Sun Qiankun , Zhang Ji , Shih Weichung J.
Published: July 2008

Different from the use of intention‐to‐treat (ITT) analysis for efficacy evaluation, many pharmaceutical companies currently use treatment emergent (TE) analysis for adverse event (AE) safety analysis. In the TE analysis, study period and AEs occurring after a pre‐specified post‐treatment window will not be included. One consideration for using the TE AE analysis is that including substantial off‐drug period and events in the analysis may dilute the power for detecting safety signals especially if after discontinuation residual treatment effect diminishes quickly. We perform quantitative analyses to compare the unbiasedness and power of the ITT and TE AE analyses under several different settings and metrics (difference in rates and relative risk). Results show that unbiasedness and power are not always in the same direction. The choice of an approach for a particular trial should depend on the focus of the analysis. A data example is used to illustrate these points. Copyright © 2008 John Wiley & Sons, Ltd.
Bayesian transformation cure frailty models with multivariate failure time data
Authors: Yin Guosheng
Published: July 2008

We propose a class of transformation cure frailty models to accommodate a survival fraction in multivariate failure time data. Established through a general power transformation, this family of cure frailty models includes the proportional hazards and the proportional odds modeling structures as two special cases. Within the Bayesian paradigm, we obtain the joint posterior distribution and the corresponding full conditional distributions of the model parameters for the implementation of Gibbs sampling. Model selection is based on the conditional predictive ordinate statistic and deviance information criterion. As an illustration, we apply the proposed method to a real data set from dentistry. Copyright © 2008 John Wiley & Sons, Ltd.
Performance implications of delayed competitive responses: evidence from the U.S. retail industry
Authors: Boyd Jens L. , Bresser Rudi K. F.
Published: July 2008

The timing of competitive actions and responses is a key management concern that has important performance consequences. This study focuses on the timing and consequences of competitive responses. Theory predicts a negative linear relationship between response delay and responder performance mirrored by an opposing positive linear relationship between response delay and first mover performance. In contrast, our study suggests that response delay has a curvilinear relationship with responder performance, and a linear relationship with first mover performance. We test our propositions using retail industry data and discuss the implications. Copyright © 2008 John Wiley & Sons, Ltd.
Extended firewall for regression testing: an experience report
Authors: White Lee , Jaber Khaled , Robinson Brian , Rajlich Václav
Published: July 2008

Testing firewalls have proven to be a useful approach for regression testing in both functional and object‐oriented software. They involve only the modules that are closely related to the changed modules. They lead to substantially reduced regression tests but still are very effective in detecting regression faults. This paper investigates situations when data‐flow paths are longer, and the testing of modules and components only one level away from the changed elements may not detect certain regression faults; an extended firewall considers these longer data paths. We report empirical studies that show the degree to which an extended firewall detected more faults, and how much more testing was required to achieve this increased detection. Copyright © 2008 John Wiley & Sons, Ltd.
Die zweite Geo‐Geum‐Brücke in Südkorea – Schrägkabelbrücke und Vorlandbrücke für Straßenverkehr mit Verbundfachwerkträger
Authors: Hopf Siegfried , Patsch Armin
Published: July 2008

Die zweite Geo Geum Grand Bridge wird Teil der festen Verbindung zwischen Geo Geum Island und der Koreanischen Halbinsel sein (Bild 1). Diese Hochbrücke setzt sich zusammen aus einer 912 m langen Vorlandbrücke und einer 1116 m langen Schrägseilbrücke mit einer Hauptspannweite von 480 m. Die Vorlandbrücke ist ein Durchlaufträger mit typischen Spannweiten von 120 m. Der Überbau beider Brücken ist ein Verbundfachwerkträger mit Betonfahrbahnplatte im Obergurt für 2‐spurigen Straßenverkehr und einem unten liegenden Fußgänger‐ und Radweg. Die Entwurfsgrundlagen für diese Brücke waren: Funktionalität als Straßenbrücke, ein innovativer Entwurf und gute Einbindung in die Umgebung. Die gebündelte Fächerform der in der Mittelebene angeordneten Schrägkabel gibt dieser Brücke ein besonderes und einzigartiges Aussehen.
Versuche an genieteten Brückenlängsträgern – Statisches Verhalten, Ermüdungsfestigkeit und Rissausbreitung
Authors: Taras Andreas , Greiner Richard
Published: July 2008

Die Bewertung der Tragfähigkeit und Restlebensdauer bestehender Eisenbahn‐ und Straßenbrücken gewinnt in den letzten Jahren immer mehr an Bedeutung. Bei der Ausarbeitung der Richtlinie ONR 24008 stellte sich daher erneut die Frage nach der Festigkeit genieteter Bauteile älterer Stahlbrücken. Im Laufe dieses Forschungsvorhabens wurden am Labor für Konstruktiven Ingenieurbau (LKI) in Zusammenarbeit mit dem Institut für Stahlbau und Flächentragwerke der Technischen Universität Graz statische Versuche und Ermüdungsversuche an genieteten Bauteilen aus einem abgetragenen Brückentragwerk desÖBB‐Netzes durchgeführt. Die Auswertung dieser Versuche gab zusätzlichen Einblick in das Tragverhalten zusammengesetzter genieteter Bauteile, besonders in das Rissfortschrittsverhalten bei Ermüdung.
Durchknöpftragfähigkeit der Verbindungen von Aluminiumtrapezprofilen und Aluminiumwellprofilen bei Befestigung im anliegenden Gurt
Authors: Misiek Thomas , Saal Helmut
Published: July 2008

Das Durchknöpfversagen von Verbindungen bei Aluminiumtrapezprofilen und Aluminiumwellprofilen unterscheidet sich vom Durchknöpfversagen vergleichbarer Verbindungen bei Stahlprofilen. Die Gründe für diese Unterschiede und die sich daraus ergebenden Konsequenzen werden hier erläutert. Auf Grundlage der beobachteten Versagensmodi und einiger grundsätzlicher Aspekte wird ein neuer Ansatz zur rechnerischen Ermittlung der Durchknöpftragfähigkeit von Verbindungen entwickelt, der gegenüber DIN 18807‐6 ohne einen Verlust an Sicherheit die Genauigkeit der Vorhersage der Tragfähigkeit signifikant verbessert.
Auswirkung von monotoner und zyklischer Belastung auf die Undichtheit eines Tankbodenecks
Authors: Wasicek Manfred , Fischer Franz Dieter , Kolednik Otmar
Published: July 2008

Das geschweißte Tankbodeneck eines vertikalen Lagertanks ist eine der gefährdetsten Stellen des Tanks. Füllen und Entleeren oder Erdbeben führen durch das Abheben des Tankbodenecks zu hohen plastischen Dehnungen im Schweißnahtbereich des Tankbodenecks. Einbrandkerben am Übergang von der Kehlnaht zum Grundmaterial verursachen Risse im Kerbgrund, die wachstumsfähig sind und die Undichtheit des Tanks zur Folge haben. Ein geo‐metrisch und materiell nichtlineares Finite‐Elemente‐Modell für zwei typische Tankgeometrien (hoher und breiter Tank) wird vorgestellt und mit der Ermittlung der Risstriebkraft (J‐Integral) für Risse im Grund von gegebenen Kerben kombiniert. Bei monotoner Belastung werden die berechneten J‐Integrale mit experimentell ermittelten J‐Integral‐Rissverlängerungswerten verglichen und kritische Kerb‐ und Risstiefen festgestellt. Bei zyklischer Belastung wird ein Low‐Cycle‐Fatigue‐Konzept für einen wachstumsfähigen Riss im Kerbgrund vorgestellt. Zusätzlich wird ein Schädigungsindikator aktiviert. Die Ergebnisse werden zu einer Aussage über die mögliche Undichtheit infolge intensiver plastischer Verformung in Verbindung mit Risswachstum zusammengefasst.
Systems engineering leading indicators for assessing program and technical effectiveness
Authors: Rhodes Donna H. , Valerdi Ricardo , Roedler Garry J.
Published: July 2008

This paper discusses a 3‐year initiative to transform classical systems engineering (SE) measures into leading indicators, including the resulting guidance information that has been developed and future research directions. Systems engineering leading indicators are measures for evaluating the effectiveness of the systems engineering activities on a program in a manner that provides information about impacts that are likely to affect the system or program performance objectives. A leading indicator may be an individual measure, or collection of measures, that is predictive of future system performance before the performance is realized. Contrary to simple status oriented measures typically used on most projects, leading indicators are intended to provide insight into the probable future state, allowing projects to improve the management and performance of complex programs before problems arise. This paper discusses the motivations and collaborative development of the SE leading indicators. It defines the leading indicator construct, introduces the initial set of 13 indicators, and provides guidance for implementation, analysis, and interpretation of these indicators. The initial set of indicators, developed through a collaboration of industry, government, and academia, has recently undergone validation through pilot studies and surveys. This work serves as a foundation for industry implementation and for further research to improve and expand the set of indicators, including development of a better understanding of how to best implement and use the leading indicators in a given program context. © 2008 Wiley Periodicals, Inc. Syst Eng
Umbilical venous blood flow measurement: accuracy and reproducibility
Authors: Figueras F. , Fernández S. , Hernández‐Andrade E. , Gratacós E.
Published: July 2008

Umbilical venous blood flow could be considered a direct and physiological measurement of vascular placental function, representing the quantity of oxygen and nutrients reaching the fetus. The advent of high‐technology ultrasound and pulsed Doppler has overcome some of the limitations of early studies. Indeed, Doppler measurement of umbilical venous blood flow has been found to be accurate when compared with several gold standards for in‐vivo flow calculation. Nevertheless, small errors in volume flow components, the vessel area and the mean velocity, result in large errors in the calculation of volume flow. Therefore, technique standardization is of paramount importance. Validation studies in animal models have demonstrated accurate venous blood flow measurements by estimating the vessel's cross‐sectional area from perpendicular views of longitudinal sections of free‐floating portions of the cord. On the other hand, estimation of the mean velocity from the maximum velocity, rather than using the intensity‐weighted mean velocity, is less software‐dependent and more clearly defined, yielding estimates with more predictable and systematic errors. By adhering to stringent methodological recommendations, umbilical venous blood flow calculation has moderate to good intra‐ and interobserver reproducibility. Having been found to be accurate and reproducible, further studies are required to establish the clinical value of umbilical vein flow measurement. Copyright © 2008 ISUOG. Published by John Wiley & Sons, Ltd.
Performance evaluation of the MAC protocol in IEEE 802.16 systems with data and VoiP traffic scheduling
Authors: Fantacci Romano , Tarchi Daniele , Bardazzi Marco
Published: July 2008

In the last few years, the metropolitan area networks (MAN) have increased their popularity and attracted the interest of the most important research groups all over the world. Among several standards, IEEE 802.16 has taken a relevant role providing high data rate in a big covering range with low implementation costs and multi‐traffic communications. The IEEE 802.16 networks can have a pre‐defined structure, with a central base station (BS) covering a cell in which a variable number of subscriber stations (SSs) can work. This paper deals with the proposal of a quality of service (QoS) driven scheduling algorithm to be used in an IEEE 802.16 network where different traffic types coexist. In particular, the paper mainly focuses on best effort data and VoIP communications, by proposing a scheduling technique that allows an efficient resource management of both traffic types by considering their specific QoS flavor. The performance evaluation has been carried out by considering both the phases of contention and packet scheduling, by means of a theoretical approach and computer simulations. Numerical results show the performance of the proposed algorithm by focusing on a scenario where the BS schedules the best effort and VoIP traffics of several SSs. Copyright © 2008 John Wiley & Sons, Ltd.
Target localization and tracking in noisy binary sensor networks with known spatial topology
Authors: Xiangqian Liu , Gang Zhao , Xiaoli Ma
Published: July 2008

Target localization and tracking are two of the critical tasks of sensor networks in many applications. Conventional localization and tracking techniques developed for wireless systems that rely on direction‐of‐arrival (DOA) or time‐of‐arrival (TOA) information are not suitable for low‐power sensors with limited computation and communication capabilities. In this paper, we propose a low‐complexity and energy‐efficient method for target localization and tracking in noisy binary sensor networks, where the sensors can only perform binary detection, and the physical links are characterized by additive white Gaussian noise (AWGN) channels. The proposed method is based on known spatial topology. An efficient wake‐up strategy is used to activate a particular group of sensors for cooperative localization and tracking. We analyze the localization error probability and tracking miss probability in the presence of prediction errors. Simulation results validate the theoretic analysis and demonstrate the effectiveness of the proposed approach. Copyright © 2008 John Wiley & Sons, Ltd.
Coverage and connectivity in three‐dimensional underwater sensor networks
Authors: Alam S. M. Nazrul , Haas Zygmunt J.
Published: July 2008

Unlike a terrestrial network, an underwater sensor network can have significant height which makes it a three‐dimensional network. There are many important sensor network design problems where the physical dimensionality of the network plays a significant role. One such problem is determining how to deploy minimum number of sensor nodes so that all points inside the network is within the sensing range of at least one sensor and all sensor nodes can communicate with each other, possibly over a multi‐hop path. The solution to this problem depends on the ratio of the communication range and the sensing range of each sensor. Under sphere‐based communication and sensing model, placing a node at the center of each virtual cell created by truncated octahedron‐based tessellation solves this problem when this ratio is greater than 1.7889. However, for smaller values of this ratio, the solution depends on how much communication redundancy the network needs. We provide solutions for both limited and full communication redundancy requirements. Copyright © 2008 John Wiley & Sons, Ltd.
Mitochondrial inheritance and fermentative : oxidative balance in hybrids between Saccharomyces cerevisiae and Saccharomyces uvarum
Authors: Solieri Lisa , Antúnez Oreto , Pérez‐Ortín Josè Enrique , Barrio Eladio , Giudici Paolo
Published: July 2008

Breeding between Saccharomyces species is a useful tool for obtaining improved wine yeast strains, combining fermentative features of parental species. In this work, 25 artificial Saccharomyces cerevisiae × Saccharomyces uvarum hybrids were constructed by spore conjugation. A multi‐locus PCR–restriction fragment length polymorphism (PCR–RFLP) analysis, targeting six nuclear gene markers and the ribosomal region including the 5.8S rRNA gene and the two internal transcribed spacers, showed that the hybrid genome is the result of two chromosome sets, one coming from S. cerevisiae and the other from S. uvarum. Mitochondrial DNA (mtDNA) typing showed uniparental inheritance in all hybrids. Furthermore, sibling hybrids, obtained by repeated crosses between the same parental strains, showed the same mtDNA, suggesting that the mitochondrial transmission is not stochastic or species‐specific, but dependent on the parental strains. Finally four hybrids, two of which with S. cerevisiae mtDNA and two with S. uvarum mtDNA, were subjected to transcriptome analysis. Our results showed that the hybrids bearing S. cerevisiae mtDNA exhibited less expression of genes involved in glycolysis/fermentation pathways and in hexose transport compared to hybrids with S. uvarum mtDNA. Respiration assay confirmed the increased respiratory activity of hybrids with the S. cerevisiae mtDNA genome. These findings suggest that mtDNA type and fermentative : respiratory performances are correlated in S. cerevisiae × S. uvarum hybrids and the mtDNA type is an important trait for constructing new improved hybrids for winemaking. Copyright © 2008 John Wiley & Sons, Ltd.
Relatedness of medically important strains of Saccharomyces cerevisiae as revealed by phylogenetics and metabolomics
Authors: MacKenzie Donald A. , Defernez Marianne , Dunn Warwick B. , Brown Marie , Fuller Linda J. , de Herrera Santiago R. M. Seco , Günther Andreas , James Steve A. , Eagles John , Philo Mark , Goodacre Royston , Roberts Ian N.
Published: July 2008

Ten medically important Saccharomyces strains, comprising six clinical isolates of Saccharomyces cerevisiae and four probiotic strains of Saccharomyces boulardii, were characterized at the genetic and metabolic level and compared with non‐medical, commercial yeast strains used in baking and wine‐making. Strains were compared by genetic fingerprinting using amplified fragment length polymorphism (AFLP) analysis, by ribosomal DNA ITS1 sequencing and by metabolic footprinting using both direct injection mass spectrometry (DIMS) and gas chromatography–time of flight–mass spectrometry (GC–ToF–MS). Overall, the clinical isolates fell into different groupings when compared with the non‐medical strains, with good but not perfect correlation amongst strains at both the genetic and metabolic levels. Probiotic strains of S. boulardii that are used therapeutically to treat human gastro‐intestinal tract disorders showed tight clustering both genetically and metabolically. Metabolomics was found to be of value both as a taxonomic tool and as a means to investigate anomalous links between genotype and phenotype. Key discriminatory metabolites were identified when comparing the three main groups of clinical, probiotic and non‐medical strains and included molecules such as trehalose, myo‐inositol, lactic acid, fumaric acid and glycerol 3‐phosphate. This study confirmed the link between a subset of clinical isolates and baking or probiotic strains but also highlighted that in general the clinical strains were more diverse at both the genomic and metabolic levels. Copyright © 2008 John Wiley & Sons, Ltd.
A concise analytical treatment of elastic‐plastic bending of a strain hardening curved beam
Authors: Eraslan A.N. , Arslan E.
Published: July 2008

Plane stress and plane strain analytical solutions to partially plastic deformation of a curved beam are presented. The beam has a narrow rectangular cross section and it is subjected to couples at its end sections prevailing pure bending conditions. The analysis is based on Tresca's yield criterion, its associated flow rule and linear strain hardening material behavior. The solutions are verified in comparison to the ones available in the literature. It is shown that plane stress and plane strain solutions agree well in the elastic and in the elastic‐plastic deformation stages. It is also observed that the changes in the dimensions of the beam as it deforms are negligibly small.
Asymptotic expansions and attractive invariant manifolds of strongly damped mechanical systems
Authors: Stumpp Th.
Published: July 2008

We study analytical properties of strongly damped mechanical systems, for which the equations of motion form a singular singularly perturbed system. We show that slow solutions can be represented by an asymptotic expansion in powers of the reciprocal of the damping parameter. Further it is shown that the strong damping forces the motion to run into an invariant manifold at an exponential rate.
Remnant population dynamics in the facultative biennial Carum carvi in fragmented semi‐natural grasslands
Authors: Kiviniemi Katariina
Published: July 2008

Transition matrix models were used to examine the population dynamics in the facultative biennial Carum carvi L. in semi‐natural grasslands, specifically to assess what life cycle stages are important for population development and to evaluate the effects of environmental stochasticity on population persistence and, hence, the ability to develop remnant populations. The demographic studies were conducted over a 4‐year period in three moderately grazed grasslands that differed in onset and duration of grazing. Experimental seed‐sowing was also conducted in disturbed and undisturbed plots in the populations. Deterministic and stochastic models yielded overall negative population growth (λ < 1) for the populations. λ was sensitive to transitions in the most frequent vegetative stage classes. Elasticity analysis indicated that a large proportion of population growth could be ascribed to the stasis of individuals in the largest vegetative stage class. Life‐table response experiment (LTRE) analyses showed also that progression to larger stage classes was important in explaining the between‐population variation in λ. The expected time to extinction was on the order of several decades for the study populations. Seed‐sowing indicated that seedling establishment was limited by both seed and micro‐site availability. The populations of C. carvi seem to be able to persist for a rather long time in moderately grazed semi‐natural grasslands, even in cases where populations are destined to become extinct. The results, thus, indicate that “biennials” are able to maintain remnant populations in managed semi‐natural grasslands.
Cause of egg mortality in azuki bean weevils (Callosobruchus chinensis): physical or chemical?
Authors: Fujii Koichi
Published: July 2008

The cause of high egg mortality at high adult density in azuki bean weevil is still controversial. It may be physical, as a result of adult trampling, or chemical, as a result of substance(s) secreted by adults and coated on the bean surface. In this study, I first constructed simple mathematical models based on each mechanism, which could predict the change of egg hatchability oviposited on different dates at different adult densities. I then devised an experimental method that could identify the fate of eggs oviposited on different dates. The experimental results showed that egg mortality was most likely caused by adult trampling.
Factors affecting large‐scale distribution of the Bonelli's eagleAquila fasciatain Spain
Authors: Carrascal Luis M. , Seoane Javier
Published: July 2008

We analyzed the environmental determinants of the regional distribution of Bonelli's eagle (Aquila fasciata) in Spain (ca. 500,000 km2), taking into account its frequency of occurrence on UTM blocks of 50 × 50 km. We found that the distribution pattern of Bonelli's eagle was a highly predictable phenomenon based on climate, vegetation and interspecific relationships. The proportion of sunny, anticyclonic days, per year (i.e., high levels of solar radiation) was the main environmental predictor explaining the distribution and abundance pattern of the Bonelli's eagle. Sparse plant formations (mainly shrublands) had also a positive effect, while altitude, agricultural land and deciduous forests had a negative influence. The relative abundance of one of its main preys, the Red Partridge (Alectoris rufa), favored the probability of occurrence of Bonelli's eagle, but only in the less sunny areas located in the north of Spain. The relative abundance of its main competitor, the Golden eagle (Aquila chrysaetos), was slightly but positively correlated with both the distribution and the abundance of the Bonelli's eagle in the Spanish portion of the Iberian Peninsula, probably due to similarities in their habitat preferences. Finally, we did not find further regional effects of the variables describing the degree of human pressure (density of roads, urban cover, and length of power lines).
Synthesis and Properties of Novel Antifungal Gemini Compounds Derived from N‐Acetyl Diethanolamines
Authors: Murguía Marcelo C. , Machuca Laura M. , Lurá María C. , Cabrera María I. , Grau Ricardo J.
Published: July 2008

A series of new N‐acetylated non‐ionic and cationic gemini surfactants (3a–f) having dimeric structures derived from primary and tertiary amines with variably long tails (C8–C12–C18) were synthesized. In addition, N‐acetylated monomeric analogues 6a and 6b were prepared and their antifungal potency and surface properties were also determined. Critical micelle concentration (CMC), effectiveness of surface tension reduction (γCMC), surface excess concentration (Γ), and area per molecule at the interface (A) were also determined and the resulting values indicate that the cationic series is characterized by good surface‐active and self‐aggregation properties. For the first time, all surfactants were tested to evaluate their antifungal properties using the method for the broth macrodilution test (M27‐A2, NCCLS). Four microbial strains were used to perform the study: Candida parapsilosis (ATCC 22019), C. albicans (ATCC 64548), and a wild‐type strain of C. parasilosis and Saccharomyces cerevisiae (ATCC 9763). The antimicrobial activity was measured by yeast growth inhibition expressed as minimum inhibitory concentration (MIC) values. Results were compared to those obtained for their monomeric analogues and for a commercially available reference compound (Fluconazole). Gemini 3b, 3e and 3f were found to be the most potent compounds. The results show S. cerevisiae as the most sensitive strain. In contrast, the wild strain of C. parapsilosis was resistant.
Microencapsulation of a Low‐trans Fat in Trehalose as Affected by Emulsifier Type
Authors: Álvarez Cerimedo María S. , Cerdeira Marina , Candal Roberto J. , Herrera María L.
Published: July 2008

A low‐trans fat blend formulated with high linoleic sunflower seed oil (SFO) and a high melting fraction (HMF) of milk fat was encapsulated by freeze‐drying emulsions. The selected emulsifiers were a mixed of the palmitic sucrose esters (SE) P‐170 and P‐1670, sodium caseinate (NaCas) or a blend of SE and NaCas. The ability to retain the core material with time was studied by storing the powders at different water activities (aw). Efficiency of encapsulation was strongly dependent on emulsifier type. NaCas formulation was more efficient retaining core material during storage. The formulation with a protein and a small surfactant had the lowest performance. The stabilizer also influenced droplet size distribution and matrix crystallinity. For NaCas‐stabilized powder volume weighted mean diameter (D4,3) remained small for up to 2 months of storage (0.56 ± 0.5 μm) and then grew notably in agreement with matrix collapse. There were no significant differences in D4,3 with water content. For NaCas/SE‐stabilized powder, however, D4,3 was high at the beginning (100 ± 0.5 μm) and then decreased most likely due to particle break‐up. Although particle size distribution showed the same behavior for all aw, retention was strongly dependent on water content. Retention with time was determined by the counteracting effects of these factors.
Abrogation of G2/M arrest sensitizes curcumin‐resistant hepatoma cells to apoptosis
Authors: Wang Wei-Zhang , Cheng Jiasen , Luo Jing , Zhuang Shi-Mei
Published: July 2008

In this study, we showed that curcumin treatment resulted in activation of Chk1‐mediated G2 checkpoint, which was associated with the induction of G2/M arrest and the resistance of cancer cells to curcumin‐induced apoptosis. Further investigation revealed that inhibition of Chk1 significantly abrogated G2/M arrest and sensitized curcumin‐resistant cells to apoptosis via upregulation of Bad and in turn the loss of mitochondrial membrane potential. These results indicate that Chk1‐mediated G2/M arrest may serve as a mechanism for curcumin resistance and Chk1 represents a potential target for the reversal of this resistance. Our findings should be helpful for clinical application of curcumin.
Identification of a rare subset of adipose tissue‐resident progenitor cells, which express CD133 and TRPC3 as a VEGF‐regulated Ca2+ entry channel
Authors: Poteser Michael , Graziani Annarita , Eder Petra , Yates Ameli , Mächler Heinrich , Romanin Christoph , Groschner Klaus
Published: July 2008

VEGF‐induced Ca2+ signalling was investigated in CD133+/VEGFR‐2+ progenitor cells isolated from human adipose stroma. Colonies derived from CD133+ immunoselected cells displayed inhomogenous Ca2+ signals, with variable magnitude of VEGF‐induced Ca2+ entry, which positively correlated with expression of the Ca2+ channel protein TRPC3. High levels of VEGF‐induced Ca2+ entry and TRPC3 expression were preferentially detected in rim areas of expanding colonies. Dominant negative suppression of TRPC3 inhibited VEGF‐induced Ca2+entry into CD133+ cells. Our results identify TRPC3 as a key Ca2+ entry channel in a subset of CD133+ stem cells. We suggest TRPC3 as an essential determinant of cell fate in CD133+ progenitor‐derived colonies.
Dependence of trans‐ADP‐ribosylation and nuclear glycolysis on the Arg 34–ATP complex of Zn2+ finger I of poly‐ADP‐ribose polymerase‐1
Authors: Kun Ernest , Kirsten Eva , Hakam Alaeddin , Bauer Pal I. , Mendeleyev Jerome
Published: July 2008

The supernatant of non‐malignant cells was replaced by glycolytic enzymes as ADP‐ribose acceptor. The hexokinase activity of the supernatant increased when OXPHOS of intact cells was uncoupled by carbonyl cyanide 4‐(trifluoro methoxy) phenylhydrazone. trans‐ADP‐ribosylation was demonstrated by polyacrylamide gel electrophoresis.
Surface Plasmons of Metal Nanostructure Arrays: From Nanoengineering to Active Plasmonics
Authors: Zheng Yue Bing , Huang Tony Jun
Published: July 2008

We developed cost-effective and high-throughput techniques to fabricate metal nanostructure arrays of various geometries on solid substrates. Surface plasmons of these nanostructure arrays were investigated both experimentally and theoretically. We systematically studied the effects of different parameters on the localized surface plasmon resonance of the nanostructure arrays. We further developed a few approaches to tailor surface plasmons for different applications. As an example of the applications of these nanostructure arrays, we demonstrated all-optical plasmonic switches/modulators based on long-range ordered Au nanodisk arrays and photoresponsive liquid crystals. The advantages of such arrays include low-cost, high-throughput, and tailorable plasmonic properties. These arrays can serve as a platform that will stimulate further progress in both fundamental research and engineering applications of plasmonics.
Development of a Molecular Assay for Rapid Screening of Chemopreventive Compounds Targeting Nrf2
Authors: Wang Zhaohui , Gidwani Vinay , Sun Zheng , Zhang Donna D. , Wong Pak Kin
Published: July 2008

Emerging molecular studies have shown that the transcription factor NF-E2-related factor (Nrf2) plays an essential role in cancer chemoprevention. Here, we report the development of a molecular biosensor for rapid detection of antioxidant-responsive element (ARE)-bound Nrf2 protein. The development will provide a molecular assay for high-throughput screening of chemopreventive compounds. Specifically, a double-stranded DNA probe is designed based on the ARE sequence. One of the DNA strands is labeled with a fluorophore on the 5′ end and the complementary strand is labeled with a quencher on the 3′ end. A single-stranded DNA competitor is also designed. The existence of the Nrf2 stabilizes the fluorescent probes and delays the competitor from separating the fluorophore-quencher complex. Therefore, the concentration of the Nrf2 proteins can be measured quantitatively based on the fluorescence intensity. The molecular binding scheme was demonstrated using purified p50 and the detection of endogenous Nrf2 was demonstrated using whole-cell lysates treated with sulforaphane. The assay can easily be incorporated into an automated platform for high-throughput screening of chemopreventive compounds targeting Nrf2.
A Novel In-Plane Microfluidic Mixer Using Vortex Pumps for Fluidic Discretization
Authors: Lei Kin Fong , Li Wen J.
Published: July 2008

Anovel in-plane microfluidic mixer based on fluidic discretization using vortex micropumps integrated in an optically transparent microfluidic substrate is presented in this article. The design, fabrication, simulation, and experimental results are described of this integrated micromixer. The basic working principle of the discretized fluidic mixer is to manipulate fluids as discretized volumes and inject them to an expansion chamber. Due to increase interfacial surface area of the discretized fluid “chunks,” the diffusion between these fluids can be completed in a shorter time, and the fluids can be mixed instantly without additional external energy. A numerical simulation was performed to emulate the flow field and mixing phenomenon to understand the results obtained by various flow experiments. Experimental results of discretized mixing have been successfully shown to have almost an ideal mixing performance and shown reasonably good match with the simulation results. Moreover, a dimensionless governing parameter (mixing index) was used to estimate the mixing performance in our system. This parameter is shown to be useful for the design and analyses of discretized mixing systems. Because this discretized mixing system requires simple mechanical structures, it provides flexibility for integrate with other microfluidic components. Also, optically transparent and biocompatible material was used to fabricate the microfluidic system, hence this micromixing system could be used to develop future fully automated biomedical and chemical “lab-on-chip” systems.
Patterning Functional Proteins with High Selectivity for Biosensor Applications
Authors: Li Nan , Ho Chih-Ming
Published: July 2008

In this article, two-dimensional hexamethyldisilazane (HMDS) micropatterns were generated on glass substrates using photolithographic techniques for the assembly of functional proteins. The non-HMDS patterned areas were backfilled with poly(ethylene glycol) (PEG) silane to reduce the nonspecific protein adsorption. The hydrophobic methyl-terminated HMDS monolayer was verified to be favorable for physical protein adsorption with bovine serum albumin (BSA). The PEG-silane derivatized surface significantly reduced the BSA nonspecific binding by 97% compared to the pristine glass substrate so that high patterning selectivity was achieved. A universal streptavidin template was generated using preadsorbed biotinylated BSA on HMDS surface to sequentially bind additional biotinylated antibodies. Using this patterning strategy, the biotinylated goat anti-mouse (biotin-GAM) antibodies can be specifically recognized by the fluorescently labeled mouse immunoglobulin G, which indicated that the immobilized biotin-GAM was still bioactive. Also, the immobilized alkaline phosphatase was demonstrated to retain its enzymatic functionality by the ability to convert its fluorogenic substrate fluorescein diphosphate into fluorescent products. This simple and effective protein patterning technique can also be extended to create nanoscale protein arrays. Additionally, its adaptability for the assembly of arbitrary proteins and antibodies provides great potentials for biosensor and biomicroelectromechanical systems (MEMS) applications.