bluuebunny/crossref_metadata_2025 huggingface dataset:
An Erythropoietin Autocrine/Paracrine Axis Modulates the Growth and Survival of Human Prostate Cancer Cells
Authors: Jeong Jee-Yeong , Hoxhaj Gerta , Socha Amanda L. , Sytkowski Arthur J. , Feldman Laurie
Published: July 2009

Erythropoietin receptors have been identified on a variety of cancer-derived cell lines and primary cancer cells, including those of prostate cancer. The functional status of these extrahematopoietic erythropoietin receptors remains a matter of some dispute. The publication of several important clinical trials suggesting a direct effect of erythropoietin on the growth and survival of primary tumors adds further importance to the question of whether erythropoietin receptors on cancer cells are functional. We have reported previously that human prostate cancer cell lines and primary prostate cancer cells express functional erythropoietin receptors that respond to exogenous erythropoietin by increased cell proliferation and STAT5 phosphorylation. We now show that prostate cancer cell lines express both the EPO gene and the biologically active erythropoietin. The coexpression of functional receptor and biologically active ligand in the cells has led us to hypothesize an autocrine/paracrine mechanism, driven by endogenous erythropoietin, which may modulate the growth and progression of prostate cancer. To test our hypothesis, we have knocked down, independently, erythropoietin receptor and erythropoietin on prostate cancer cells by transfection with short hairpin RNAs. Erythropoietin receptor knockdown cells grow significantly more slowly than their erythropoietin receptor-bearing counterparts in monolayer culture, produce fewer, smaller colonies in soft agar, and do not exhibit erythropoietin-induced signaling. Erythropoietin knockdown cells exhibit dramatically slower rates of growth, which could be restored by transfecting the cells with a murine erythropoietin gene. Taken together, our data suggest that the coordinated regulation of a functional erythropoietin/erythropoietin receptor axis in prostate cancer cells may be integral to the growth and progression of prostate cancer. (Mol Cancer Res 2009;7(7):OF1–8) (Mol Cancer Res 2009;7(7):1150–7)
Vascular Caveolin Deficiency Supports the Angiogenic Effects of Nitrite, a Major End Product of Nitric Oxide Metabolism in Tumors
Authors: Frérart Françoise , Lobysheva Irina , Gallez Bernard , Dessy Chantal , Feron Olivier
Published: July 2009

The biological status of nitrite recently evolved from an inactive end product of nitric oxide (NO) metabolism to a major intravascular and tissue storage of NO. Several enzymes and proteins may indeed work as nitrite reductases. The endothelial NO synthase (eNOS) is proposed to be one of them, particularly when oxygen is lacking. Here, we examined whether the lack of caveolin, a scaffold protein known to limit eNOS activity under basal conditions and to be down-regulated in tumor vessels, could favor the reconversion of nitrite into NO and thereby promote angiogenesis. We found that nitrite-rich serum from caveolin-deficient mice and exogenous nitrite exert proangiogenic effects on aortic explants cultured in a three-dimensional collagen matrix. We identified a higher intrinsic capacity of caveolin-deficient vessels and endothelial cells to convert nitrite into bioactive NO. These effects did occur under moderate hypoxia and were abolished on exposure to a NO scavenger. Evidence for eNOS acting as a nitrite reductase derived from the failure to reproduce the proangiogenic effects of nitrite on eNOS-deficient aorta rings and endothelial cells. Finally, in a mouse tumor model, we documented the higher nitrite content in hypoxic tumors and identified inducible NO synthase as the major source of nitrite. Altogether, these data identify the lack of caveolin observed in the tumor vasculature as a favorable ground for nitrite-driven formation of endothelial tubes in the hypoxic tumor microenvironment. This work also strengthens the therapeutic value of the modulation of caveolin expression to interfere with tumor angiogenesis. (Mol Cancer Res 2009;7(7):1056–63)
Usefulness of the SYNTAX Score for Predicting Clinical Outcome After Percutaneous Coronary Intervention of Unprotected Left Main Coronary Artery Disease
Authors: Capodanno Davide , Di Salvo Maria Elena , Cincotta Glauco , Miano Marco , Tamburino Claudia , Tamburino Corrado
Published: July 2009

Background—

The SYNTAX score (SXscore) has been proposed recently as a valuable tool to characterize the coronary vasculature prospectively with respect to the number of lesions and their functional impact, location, and complexity. However, the prognostic value of SXscores in patients undergoing percutaneous coronary intervention of the left main artery has not been validated.

Methods and Results—

We applied the SXscore in 255 consecutive patients who underwent percutaneous coronary intervention for left main disease and explored its performance with respect to their clinical outcome. Univariate and multivariate Cox proportional hazard regression analyses were performed to evaluate the relation between the SXscore and the incidence of cardiac mortality, the primary end point of the study, and major adverse cardiac events (MACE). At 1 year, the SXscore significantly predicted the risk of cardiac death (hazard ratio, 1.12/unit increase; 95% CI, 1.06 to 1.18;
P
<0.001) and MACE (hazard ratio, 1.59/unit increase; 95% CI, 1.02 to 2.48;
P
=0.043). After adjustment for potential confounders, a higher SXscore remained significantly associated with cardiac mortality (adjusted hazard ratio, 1.15; 95% CI, 1.05 to 1.26;
P
=0.003) and MACE (adjusted hazard ratio, 1.06; 95% CI, 1.02 to 1.10;
P
=0.005). C-indexes for SXscores in terms of cardiac death and MACE were 0.83 and 0.64, respectively. Using classification tree analysis, discrimination levels of 34 and 37 were identified as the optimal cutoff to distinguish between patients at low and high risk of cardiac death and MACE, respectively.

Conclusions—

The SXscore is a useful tool to predict cardiac mortality and MACE in patients undergoing percutaneous revascularization of the left main coronary artery.
Effect of Temperature on Foaming Behaviors of Homo- and Co-polymer Polypropylene/Polydimethylsiloxane Blends with CO2
Authors: Qingfeng Wu  , Park Chul B. , Nanqiao Zhou  , Wenli Zhu
Published: July 2009

Poly(dimethylsiloxane) (PDMS) was blended with two different types of polypropylene (PP). The blends were subsequently batch-foamed with supercritical CO2 at a series of temperatures that varied by a narrow increment of 2°C to investigate the effect of the foaming temperature on foaming. In the case of the random copolymer PP, it was found that the cell density of the blends containing PDMS increased significantly and good cell structures could be obtained across a wide temperature spectrum. PDMS typically generated high CO2 concentration and low surface tension, which positively impacted the cell nucleation. In the case of linear homopolymer PP, the addition of PDMS did not result in any pronounced improvement to cell morphology; however, at very low temperatures, much lower than the melting point, a few very small cells appeared. In both experiments, the addition of maleic anhydride grafted PP (PP-g-MAH) as a compatibilizer promoted the dispersion of PDMS and yielded a better cell morphology within a specific temperature range. Moreover, the presence of a compatibilizer enhanced the melt strength, which in turn served to broaden the processing window.
Creating Open-celled Solid-state Foams Using Ultrasound
Authors: Xiaoxi Wang  , Wei Li  , Kumar Vipin
Published: July 2009

Open-celled solid-state foams are expected to have many applications, such as filtration, biochemical sensing, and tissue engineering scaffolding. For bio-related applications, the solid-state foaming process has a unique advantage, i.e., the process does not involve any organic solvent that could leave residues harmful to biological cells. The disadvantage, however, is that solid-state foams are mostly close-celled and do not allow biological cells or fluids to permeate through. This article presents a parametric study on a novel fabrication method to create open-celled solid-state foams using ultrasound. Biodegradable polymer was foamed in a solid-state foaming process. Ultrasound was then applied to break the pore walls. The parameters examined in this study included the pore size, ultrasound power, ultrasound frequency, and water temperature. The inter-pore connectivity was verified using permeability measurements, dye diffusion, and a degradability test. The permeability values were further used to analyze the effects of the experimental parameters. In the analysis a logistic regression model was first used to ensure sample integrity after the ultrasound treatment. A linear regression was then conducted to determine the significance of process variables. It was found that the pore size was the most significant factor affecting the ultrasound effectiveness. The bigger the pores are, the higher the permeability could be obtained with ultrasound. In order to increase the permeability of the ultrasound treated samples, high ultrasound power, high water temperature, and low ultrasound frequency should be used.
Allocation to Offending Behavior Programs in the English and Welsh Probation Service
Authors: Palmer Emma J. , Mcguire James , Hatcher Ruth M. , Hounsome Juliet C. , Bilby Charlotte A.L. , Hollin Clive R.
Published: July 2009

The Probation Service of England and Wales delivers three offending behavior programs designed for offenders who have committed any offense. One of the selection criteria for these programs states that offenders should have a medium-high risk of reoffending rather than low or very high risk. This article examines the appropriateness of offender allocation by risk level to these three programs in the Probation Service. There was significant variation in allocation performance by Probation Area and program. Appropriateness of allocation was associated with program completion. Very high—risk offenders were more likely to not start a program that they had been allocated to and more likely to not complete a program once they had started. Appropriateness of allocation also affected reconviction independently of program completion status.
Posterior Predictive Model Checking for Multidimensionality in Item Response Theory
Authors: Levy Roy , Mislevy Robert J. , Sinharay Sandip
Published: July 2009

If data exhibit multidimensionality, key conditional independence assumptions of unidimensional models do not hold. The current work pursues posterior predictive model checking, a flexible family of model-checking procedures, as a tool for criticizing models due to unaccounted for dimensions in the context of item response theory. Factors hypothesized to influence dimensionality and dimensionality assessment are couched in conditional covariance theory and conveyed via geometric representations of multidimensionality. A simulation study investigates the performance of the model-checking tools for dichotomous observables. Key findings include support for the hypothesized effects of the manipulated factors with regard to their influence on dimensionality assessment and the superiority of certain discrepancy measures for conducting posterior predictive model checking for dimensionality assessment.
Just Doing What They Gotta Do
Authors: Coles Roberta L.
Published: July 2009

For single African American custodial fathers, parenting stress is exacerbated by the cultural expectation that Black fathers are “normally” absent and by the clustering of stresses that Black men are more likely to encounter. This sample of African American fathers have used a repertoire of problem-focused and cognitive coping strategies, including some that are frequently considered “culturally specific.” Twenty Black single custodial fathers are interviewed and their narratives are analyzed for concepts and thematic categories related to stress and coping. Their narratives indicate that certain strategies are avoided because (a) these strategies are not available to them and (b) they desire to present themselves as independent and competent, thus resisting stereotypes and building a sense of efficacy.
An Exploratory Study of the Nature of Family Resilience in Families Affected by Parental Alcohol Abuse
Authors: Coyle James P. , Nochajski Thomas , Maguin Eugene , Safyer Andrew , DeWit David , Macdonald Scott
Published: July 2009

Resilient families are able to adapt to adversities, but the nature of family resilience is not well understood. This study examines patterns of family functioning that may protect families from the negative impact of alcohol abuse. Naturally occurring patterns of family functioning are identified and associations between these patterns and parenting, current parental alcohol use, recent family stressful events, supportive relationships outside the family, and demographic characteristics are assessed. Cross-sectional data are analyzed from racially diverse American and Canadian families ( N = 674) who have at least one parent with an alcohol abuse problem and a child between ages 9 and 12 years. Cluster analyses derived from family functioning indicators are used to identify naturally occurring family patterns. Multivariate assessments evaluated relationships between family functioning clusters and potentially influencing factors. The study results reveal a continuum of family functioning associated with parenting, child’s perception of teacher caring, and race.
Comparative Verification Exercises on a Probabilistic Network Model for Building Evacuation
Authors: Spearpoint M.J.
Published: July 2009

Functional testing of any model is a vital step in demonstrating that its predictive capabilities are working appropriately; correspond as expected to the circumstances being modeled and where further work should be directed. This article presents a series of exercises used to substantiate the movement prediction capability of a probabilistic network-based evacuation model that is currently under development. Two simple component configurations and two previously available worked examples are used to demonstrate that the model performs adequately. Movement times from model predictions, hand calculations, alternative empirical methods, and other computer models were compared for a range of typical occupant densities.
Perspectives on: Supercritical Fluid Technology for 3D Tissue Engineering Scaffold Applications
Authors: Duarte Ana Rita C. , Mano João F. , Reis Rui L.
Published: July 2009

Supercritical fluid technology has proven to be useful for many pharmaceutical applications and is now emerging as an alternative to conventional processes for the preparation of 3D structures and injectable particles suitable to be used in regenerative medicine. A current overview of the basic principles underlying supercritical fluid technology, the state of the art and future potential of this technology are presented.
The Genesis of Islam in the Light of History
Authors: Al-Azmeh Aziz
Published: July 2009

Faced with the choice between two themes that I suggested I might address this evening, the organisers of this event preferred me to speak as an historians' historian, rather than to opt for a topic of more general or current interest, and I have agreed to do so. Yet I should nevertheless be dissatisfied if those among you who do not particularly wish to be lectured to by historians were to be irked by an academic disquisition on some arcane matter. I shall therefore do my very best to ensure that those of you who are not historians, or who are not engaged professionally in the academic trade, shall leave this hall with somewhat more than the fleeting impression of an event. And I shall do so not least by suggesting that genesis, even the genesis of Islam, has more to do with Charles Darwin than with the Bible or the glorious associations of the Greek language, and that the reference to light in the title of my talk has more to do with reflective de-liberation than with exquisite colouration.
The Invention of Dancing Mania
Authors: Rohmann Gregor
Published: July 2009

Medieval ‘dancing mania’ has until recently remained an enigma in medical and religious history. This is because scholars tend to view it as an invariable medical syndrome instead of examining it as an example of the historicity of illness as semantic network. Taking the latter approach allows for grasping the phenomenon as a form of insanity specific to the Rhine basin of the sixteenth and seventeenth centuries, though one whose roots can be traced to the early medieval reception of platonic cosmology and ‘theurgy’. This paper examines the legend of the Kölbigk dancers in the above perspective and establishes that its chief motif goes back to Sulpicius Severus’ reception of ‘Iamblichus’ ‘de mysteriis’. Thus, dancing mania appears to have been a form of insanity, indeed, but one constructed through religious narratives.
Revisioning the Conquest of Mexico
Authors: Bröchler Anja
Published: July 2009

When the Franciscan friar Bernardino de Sahagún (1499–1590) compiled the famous encyclopaedic history of Nahua culture generally known as the Florentine Codex (1578/79–80), he relied heavily on Nahua aides. Educated in the western humanist tradition and knowledgeable about their own world, these native collaborators were crucial to Sahagún's project. This article focuses in particular on the drawings of the Florentine Codex, analysing the close relationship between text and image in Book Twelve, which tells the story of the conquest of Mexico (1519–21). The drawings have received little scholarly attention as they lack the artistic features of what was regarded as ‘classic’ indigenous pictographic writing. This article argues that the tlacuiloque, the writers/painters of Book Twelve, did not merely sprinkle some elements of indigenous pictographic writing in more European style pictures, but created a new idiom to transmit their own way of visualising intertwined histories of conquest.
Visualising the Incarnation in Medieval Christianity
Authors: Khan Sarah
Published: July 2009

Within Christian iconography and in medieval Christian cult practices, floral depictions play a major role. The genesis of such floral pictorial signs has not been addressed in art historical writing. This article attempts to trace the origins of the Christian floral iconography, investigates the perceptions and usages of such motifs in cult practices and proceeds to demonstrate the extent to which Christian sources shared a common under-standing with world religions such as Buddhism. Buddhist and Christian sources appear to have taken recourse to similar iconographic formulae in order to make abstract, invisible deities perceptible to the believer. Floral iconography in Christian cult practices was an effective medium to communicate Christ's birth through the Virgin Mary and the story of his unique Passion. By transcending common allusions to Incarnations, it is even able to transport meanings which help the believer to find consolation in his quest of the Christian afterlife.
Using a Curriculum-Based Measurement Graphic Organizer to Facilitate Collaboration in Reading
Authors: McArthur Capizzi Andrea , Barton-Arwood Sally M.
Published: July 2009

Curriculum-based measurement (CBM) is a useful tool for both general and special educators to evaluate and improve student achievement. Although it is backed by more than 30 years of research and validation, particularly in reading, many teachers still do not use CBM in their classrooms. Historically, the use of CBM to guide instructional changes is more familiar to special education teachers than to general education teachers. The purpose of this article is to provide an overview of CBM, along with a graphic organizer worksheet, to help teachers get started with using CBM in reading. First, CBM and its relationship to response to intervention (RTI) are discussed. Second, challenges to the use of CBM are addressed, and instructions for using the graphic organizer worksheet are provided. Finally, strategies are suggested to facilitate the use of CBM to enhance collaboration among general and special education teachers.
Development of a Mechanical Technology for Joining Sandwich Elements
Authors: Feldhusen Jörg , Warkotsch Christoph , Kempf Alexander
Published: July 2009

Wide spread use of sandwich structures is still inhibited by the lack of a consistent joining technology one which is easy to work with, quantifiable and not dependent on special knowledge about manufacturing processes. A mechanical technology for joining sandwiches as developed in this article shall achieve these goals. The developing process follows the design methodology according to Pahl et al. [1]. The resulting systematic approach to the problem facilitated the generation of a complete solution field. This approach led to 18 promising concepts of 783 possible original solutions. Prototypes of those concepts showed that a reliable mechanical technology for joining sandwich elements is feasible.
Fabrication and Mechanical Testing of a New Sandwich Structure with Carbon Fiber Network Core
Authors: Shahdin Amir , Morlier Joseph , Gourinat Yves , Mezeix Laurent , Bouvet Christophe
Published: July 2009

The aim is the fabrication and mechanical testing of sandwich structures including a new core material known as fiber network sandwich materials. As fabrication norms for such a material do not exist as such, the primary goal is to reproduce successfully fiber network sandwich specimens. Enhanced vibration testing diagnoses the quality of the fabrication process. These sandwich materials possess low structural strength as proved by the static tests (compression, bending), but the vibration test results give high damping values, making the material suitable for vibro-acoustic applications where structural strength is of secondary importance e.g., internal paneling of a helicopter.
Muscarinic effects and foetal cardiovascular and hormonal responses in utero
Authors: Jianli Zheng  , Weili Yang  , Li Cao  , Shigang Li  , Yuying Zhang  , Zhen Wan  , Caiping Mao
Published: July 2009

Introduction. Cholinergic mechanisms play an important role in the control of hormonal and vascular regulation. However, in utero development of cholinergic regulation in the foetal hormonal systems is not clearly understood.This study investigated foetal hormonal and cardiovascular responses following application of the muscarinic antagonist atropine.

Materials and methods. Chronically prepared near-term ovine foetuses (control and experimental: n=5, each group) were used.After 4—5 days’ surgical recovery, conscious ewes and their foetuses were tested in vivo.

Results. In response to intravenous atropine, foetal systolic, diastolic, and mean arterial pressure, as well as heart rate, increased immediately. Inhibition of muscarinic systems in the circulation caused a reduction of plasma angiotensin II levels, while angiotensin I in the circulation remained unchanged in the foetus. In addition, foetal plasma aldosterone levels were significantly increased following blockade of the cholinergic receptor, while other hormones, including arginine vasopressin, adrenocorticotrophic hormone, and atrial natriuretic peptide, were not changed in foetal blood under the same condition.

Conclusions. The results suggest that foetal automatic systems, not those hormonal factors tested, play a major role in cholinergic mechanisms mediating cardiovascular control. Furthermore, the data provide new information on how muscarinic inhibition affects renin-angiotensin system and adrenal cortex functions. Key words: aldosterone, angiotensin-converting enzyme, autonomic regulation, foetus
Potential and Limitations of a Deconvolution Approach for Guided Wave Structural Health Monitoring
Authors: Cicero T. , Cawley P. , Simonetti F. , Rokhlin S.I.
Published: July 2009

Ultrasonic guided waves offer the possibility of inspecting large areas of structures from a small number of sensor positions. However, inspection of complex structures is difficult as the reflections from different features overlap. Estimating the number and amplitude of the wave packets in ultrasonic time traces is crucial for the development of a guided wave inspection system, in order to detect and locate damage. Deconvolution has been extensively used in geophysical applications to resolve overlapping echoes in the recorded signals. The main objective of this work was to evaluate the applicability of the deconvolution approach for enhancing the resolution of ultrasonic time traces in structural health monitoring (SHM). Numerical simulations on strongly overlapping signals were carried out to evaluate the performance of the two techniques that have been considered: (i) Wiener filter, (ii) single most likely replacement. It was shown that the relatively narrow bandwidth of the input signals and phase shifts between different reflections limit the benefits obtained from deconvolution and it was concluded that deconvolution is unlikely to be useful for guided wave SHM applications.
Passive Impact Location Estimation Using Piezoelectric Sensors
Authors: Guyomar Daniel , Lallart Mickaël , Monnier Thomas , Xingjun Wang  , Petit Lionel
Published: July 2009

As part of Structural Health Monitoring (SHM), the history of a structure has become a crucial element to take into account. This has been shown, for example, by the spectacular accident of the flight Aloha 243 near Hawaï, when a whole part of the fuselage of a Boeing 737 had been torn off. Thus, monitoring impacts has become particularly interesting to give a comprehensive view of the occurrence of structural damage. Typical impact location estimation techniques use structural frequency drifts of a structure. Thus, such methods need an external excitation of the structure, which is unrealistic in most of the cases. As well, huge and possibly long computations, as genetic algorithms or artificial neural networks, are required for such techniques in order to retrieve the impact location. The scope of the this article was to present a passive impact location estimation using piezoelectric elements for a 1D infinite beam. The principles of the proposed technique was the comparison of the vibrational energy extracted by each sensor. From this comparison, the impact location was cost-efficiently estimated. Theoretical development and experimental results showed that this extraction-based force location estimation method performed well, while being very simple.
Time Domain Reflectometry Automatic Bridge Scour Measurement System: Principles and Potentials
Authors: Yu Xinbao , Yu Xiong
Published: July 2009

Bridge scour is a major factor contributing to the failures of highway bridges constructed over waterways. During flood events, sediments can be washed away and bridge substructures (piers and abutments) are left inadequately supported. Field monitoring of bridge sour process is necessary to study the scour mechanism, to develop scour-resistant design of bridge piers and abutments, to implement effective scour countermeasures, and to deploy safety warning systems. The current instruments are not completely satisfactory in providing real-time monitoring data during critical flood events. This study introduces the development of an automatic scour monitoring system using time domain reflectometry (TDR) principle. It presents the principles and system design of the TDR sediment scour monitoring system. An analyses algorithm for scour signals has been developed. It was found to be robust and can be implemented to automate scour signal interpretation. Simulated experiments were conducted to validate the performance of the scour monitoring system prototype. The results showed that this TDR technology can accurately measure the scour depth. Besides, the properties of the sediments, such as the porosity and density can be estimated with reasonable accuracy. At the end of the paper, a few important issues associated with field deployments of TDR scour monitoring system are discussed.
Development of a Real-time Remote Structural Monitoring Scheme for Civil Infrastructural Systems
Authors: Sridhar S. , Ravisankar K. , Sreeshylam P. , Parivallal S. , Kesavan K. , Murthy S.G.N.
Published: July 2009

Long-term structural monitoring has become an important requisite to ensure structural and operational safety for critical civil infrastructures. Long-term structural monitoring by acquiring data continuously or at small intervals may be difficult to achieve by employing conventional on-site monitoring methods. In order to overcome these difficulties remote structural monitoring (RSM), an advanced structural monitoring technique, can be used to acquire continuous data from the remotely instrumented structure. RSM methodology requires an interdisciplinary approach integrating areas such as structural engineering, sensor technology, communication technology, statistical mechanics, information technology for online data transmission (over larger distances) and damage detection/ health assessment of the structure. RSM has many advantages like, continuous monitoring, early alarm of any incipient damage, and data acquisition even in adverse climatic/environmental conditions. This article describes the development of an RSM scheme, developed at SERC, Chennai. The article outlines the laboratory and field investigations carried out to validate the developed scheme. Brief information about the observations and modifications made during these trials are also presented. A part of the work carried out for synthesizing online data using Auto Regressive Moving Average model is also presented.
Monitoring the Mechanical Behavior of the Weathervane Sculpture Mounted Atop Seville Cathedral’s Giralda Tower
Authors: Solís M. , Romero A. , Galvín P.
Published: July 2009

This article presents the application of monitoring and detection of structural damage techniques to a historic monument. Seville cathedral’s famous bell tower ‘La Giralda’ is 96 m tall and is crowned with a large 16th century sculpture known as ‘Giraldillo’. The sculpture is supported with an internal bar structure, which is fitted over the axis about which it rotates according to the wind direction, allowing it to function as a weathervane. Between 1999 and 2005 the Giraldillo was demounted and underwent an intensive restoration process, which included mechanical and structural repair work. As the sculpture is only accessible by means of complex and costly scaffolding systems, an instrumentation system consisting of different types of sensors was installed to study the assembly’s mechanical response, its functioning as a weathervane and its state of conservation while it was being remounted atop the Giralda Tower. Different damage detection techniques aimed at detecting possible deterioration in the Giraldillo’s support structure were employed as well. This article presents results obtained in 2 years of system operation, showing how structural heath monitoring techniques can be applied to historical monuments.
Structural Health Monitoring of a Metallic Sandwich Panel by the Method of Virtual Forces
Authors: White Jonathan R. , Adams Douglas E. , Jata Kumar
Published: July 2009

A structural health monitoring system for assessing thermal damage in a metallic sandwich panel was developed in this article. The method of virtual forces was utilized to detect, locate, and quantify damage. The method assumes that a damaged structural response is a summation of the undamaged response and the response from an effective forcing function, which represents the effects of the material damage. The effective forcing function, or virtual force, is an estimate of the forces that the damage mechanism exerts on the undamaged structure. Virtual forces were shown to detect changes in the mass, stiffness, and damping matrices in a lumped parameter dynamic model. A finite element model of a mechanically attached sandwich metallic panel was used to detect a stiffness loss at different locations between two sensor locations. These results were then compared with experimental results involving thermal debond between the face sheet and core of an Al—Al honeycomb panel. Virtual forces indicated there was damage associated with magnitude and frequency shifts in the frequency response function measurements made on the damaged panel. Damage was located relative to the sensor/actuator measurement locations. Damage that was not adjacent to measurement locations was less accurately located and quantified. Variability in producing localized thermal debond using an acetylene torch was also apparent in the virtual force estimates. The virtual force estimates also indicated that damage was spread over several measurement locations because highly localized thermal debond was difficult to produce.
Efficient Calculation of Statistical Moments for Structural Health Monitoring
Authors: Choi Myoungkeun , Sweetman Bert
Published: July 2009

Wireless networks of smart sensors with computations distributed over multiple sensor packages have shown considerable promise in providing low-cost structural health monitoring. In these networks, microprocessors are typically embedded in individual smart sensor packages. The efficiency of embedded computational algorithms is of critical importance because the size, cost, and power requirements of the sensor arrays are central concerns. Here, very efficient methodologies are presented to compute statistical moments of a measured response time-history. These moments: the mean, standard deviation, skewness, and kurtosis are often used to characterize a measured irregular response. Two alternative approaches are presented, each of which can save substantial computer memory requirements and CPU time in certain applications. The first approach reconsiders the computational benefits of computing statistical moments by separating the data into bins and then computing the moments from the geometry of the resulting histogram, which effectively becomes a one-pass algorithm for higher moments. One benefit is that the statistical moment calculations can be carried out to arbitrary accuracy such that the computations can be tuned to the precision of the sensor hardware. The second approach is a new analytical methodology to combine statistical moments from individual segments of a time-history such that the resulting overall moments are those of the complete time-history. This methodology could be used to allow for parallel computation of statistical moments with subsequent combination of those moments, or for combination of statistical moments computed at sequential times.

A worked example is presented comparing two implementations of the new methodologies with conventional calculations in monitoring the global performance of an offshore tension leg platform. Accuracy, efficiency, and storage requirements of the calculation methods are compared with those of conventional methods. The results show that substantial CPU and memory savings can be attained with no loss in accuracy and that more dramatic savings can be attained if a slight reduction in accuracy is acceptable.
Modulation of expression of innate immunity markers CXCL5/ENA-78 and CCL20/MIP3α by protease-activated receptors (PARs) in human gingival epithelial cells
Authors: Rohani Maryam G. , Beyer Richard P. , Hacker Beth M. , Dommisch Henrik , Dale Beverly A. , Chung Whasun O.
Published: July 2009

Protease-activated receptors (PARs) are G-protein-coupled receptors with an active role in host defense. The two most highly expressed members of the PAR family in gingival epithelial cells (GECs) are PAR1 and PAR2. The major virulence factors of periodontal pathogen Porphyromonas gingivalis are its proteases which can activate PAR2. However, little is known about the function of PARs in GECs when they are activated by their endogenous agonist enzymes. The purpose of this study was to characterize how the expression of innate immune markers is modulated when PAR1 and PAR2 are activated by their agonist enzymes, thrombin and trypsin, respectively. Here, we report that activation of PAR1 and PAR2 induces cell proliferation at low concentration. Activation of PAR via proteolytic activity of thrombin and trypsin induces expression of CXCL5/ENA-78 and CCL20/MIP3α in a concentration-dependent manner. Induction of CXCL5 via PAR1 was inhibited in the presence of PAR1 cleavage blocking antibodies and by PAR1 siRNA. The induction of CXCL5 and CCL20 via PAR2 was inhibited by PAR2 siRNA. These findings indicate an active role in innate immune responses by PAR1 and PAR2 in GECs. Modulation of innate immunity by PARs may contribute to co-ordinated and balanced immunosurveillance in GECs.
Gata1 expression driven by the alternative HS2 enhancer in the spleen rescues the hematopoietic failure induced by the hypomorphic Gata1low mutation
Authors: Migliaccio Anna Rita , Martelli Fabrizio , Verrucci Maria , Sanchez Massimo , Valeri Mauro , Migliaccio Giovanni , Vannucchi Alessandro Maria , Zingariello Maria , Di Baldassarre Angela , Ghinassi Barbara , Rana Rosa Alba , van Hensbergen Yvette , Fibbe Willem E.
Published: July 2009

Rigorously defined reconstitution assays developed in recent years have allowed recognition of the delicate relationship that exists between hematopoietic stem cells and their niches. This balance ensures that hematopoiesis occurs in the marrow under steady-state conditions. However, during development, recovery from hematopoietic stress and in myeloproliferative disorders, hematopoiesis occurs in extramedullary sites whose microenvironments are still poorly defined. The hypomorphic Gata1low mutation deletes the regulatory sequences of the gene necessary for its expression in hematopoietic cells generated in the marrow. By analyzing the mechanism that rescues hematopoiesis in mice carrying this mutation, we provide evidence that extramedullary microenvironments sustain maturation of stem cells that would be otherwise incapable of maturing in the marrow.
A lower risk of recurrent venous thrombosis in women compared with men is explained by sex-specific risk factors at time of first venous thrombosis in thrombophilic families
Authors: Lijfering Willem M. , Veeger Nic J. G. M. , Middeldorp Saskia , Hamulyák Karly , Prins Martin H. , Büller Harry R. , van der Meer Jan
Published: July 2009

Why men appear to have an increased risk of recurrent venous thrombosis compared with women is unknown. In a cohort study of families with thrombophilia, lifetime risk of recurrent venous thrombosis was assessed in men and women (n = 816). Adjusted relative risk of recurrence was 1.6 (95% CI, 1.3-2.0) in men compared with women. Women were younger at time of their first event (mean, 34 years vs 44 years; P < .001) and at time of recurrence (40 years vs 48 years, P < .001). After excluding provoked first and recurrent venous thrombosis, adjusted relative risk was 1.2 (95% CI, 0.8-1.7), although mean age at recurrence was comparable in men and women (50 years vs 49 years, P = .595). In women with a hormonal first event, median interval between first event and recurrence was 10.4 years versus 2.7 years in men (P < .001). This difference was not observed when only unprovoked events were considered (P = .938). The difference in lifetime risk of recurrent venous thrombosis between men and women in thrombophilic families can be explained by a younger age of women at time of first venous thrombosis due to hormonal risk factors, and a longer interval between a provoked first episode of venous thrombosis and recurrence in women.
Epigenetic regulation of the alternatively activated macrophage phenotype
Authors: Ishii Makoto , Wen Haitao , Corsa Callie A. S. , Liu Tianju , Coelho Ana L. , Allen Ronald M. , Carson William F. , Cavassani Karen A. , Li Xiangzhi , Lukacs Nicholas W. , Hogaboam Cory M. , Dou Yali , Kunkel Steven L.
Published: July 2009

Alternatively activated (M2) macrophages play critical roles in diverse chronic diseases, including parasite infections, cancer, and allergic responses. However, little is known about the acquisition and maintenance of their phenotype. We report that M2-macrophage marker genes are epigenetically regulated by reciprocal changes in histone H3 lysine-4 (H3K4) and histone H3 lysine-27 (H3K27) methylation; and the latter methylation marks are removed by the H3K27 demethylase Jumonji domain containing 3 (Jmjd3). We found that continuous interleukin-4 (IL-4) treatment leads to decreased H3K27 methylation, at the promoter of M2 marker genes, and a concomitant increase in Jmjd3 expression. Furthermore, we demonstrate that IL-4–dependent Jmjd3 expression is mediated by STAT6, a major transcription factor of IL-4–mediated signaling. After IL-4 stimulation, activated STAT6 is increased and binds to consensus sites at the Jmjd3 promoter. Increased Jmjd3 contributes to the decrease of H3K27 dimethylation and trimethylation (H3K27me2/3) marks as well as the transcriptional activation of specific M2 marker genes. The decrease in H3K27me2/3 and increase in Jmjd3 recruitment were confirmed by in vivo studies using a Schistosoma mansoni egg–challenged mouse model, a well-studied system known to support an M2 phenotype. Collectively, these data indicate that chromatin remodeling is mechanistically important in the acquisition of the M2-macrophage phenotype.
Prognostic relevance of Wnt-inhibitory factor-1 (WIF1) and Dickkopf-3 (DKK3) promoter methylation in human breast cancer
Authors: Veeck Jürgen , Wild Peter J , Fuchs Thomas , Schüffler Peter J , Hartmann Arndt , Knüchel Ruth , Dahl Edgar
Published: July 2009

Background

Secreted Wnt signaling antagonists have recently been described as frequent targets of epigenetic inactivation in human tumor entities. Since gene silencing of certain Wnt antagonists was found to be correlated with adverse patient survival in cancer, we aimed at investigating a potential prognostic impact of the two Wnt antagonizing molecules WIF1 and DKK3 in breast cancer, which are frequently silenced by promoter methylation in this disease.

Methods

WIF1 and DKK3 promoter methylation were assessed by methylation-specific PCR with bisulfite-converted DNA from 19 normal breast tissues and 150 primary breast carcinomas. Promoter methylation was interpreted in a qualitative, binary fashion. Statistical evaluations included two-sided Fisher's exact tests, univariate log-rank tests of Kaplan-Meier curves as well as multivariate Cox regression analyses.

Results

WIF1 and DKK3 promoter methylation were detected in 63.3% (95/150) and 61.3% (92/150) of breast carcinoma samples, respectively. In normal breast tissues, WIF1 methylation was present in 0% (0/19) and DKK3 methylation in 5.3% (1/19) of samples. In breast carcinomas, WIF1 methylation was significantly associated with methylation of DKK3 (p = 0.009). Methylation of either gene was not associated with clinicopathological parameters, except for DKK3 methylation being associated with patient age (p = 0.007). In univariate analysis, WIF1 methylation was not associated with clinical patient outcome. In contrast, DKK3 methylation was a prognostic factor in patient overall survival (OS) and disease-free survival (DFS). Estimated OS rates after 10 years were 54% for patients with DKK3-methylated tumors, in contrast to patients without DKK3 methylation in the tumor, who had a favorable 97% OS after 10 years (p < 0.001). Likewise, DFS at 10 years for patients harboring DKK3 methylation in the tumor was 58%, compared with 78% for patients with unmethylated DKK3 (p = 0.037). Multivariate analyses revealed that DKK3 methylation was an independent prognostic factor predicting poor OS (hazard ratio (HR): 14.4; 95% confidence interval (CI): 1.9–111.6; p = 0.011), and short DFS (HR: 2.5; 95% CI: 1.0–6.0; p = 0.047) in breast cancer.

Conclusion

Although the Wnt antagonist genes WIF1 and DKK3 show a very similar frequency of promoter methylation in human breast cancer, only DKK3 methylation proves as a novel prognostic marker potentially useful in the clinical management of this disease.
Developing a scalable model of recombinant protein yield from Pichia pastoris: the influence of culture conditions, biomass and induction regime
Authors: Holmes William J , Darby Richard AJ , Wilks Martin DB , Smith Rodney , Bill Roslyn M
Published: July 2009

Background

The optimisation and scale-up of process conditions leading to high yields of recombinant proteins is an enduring bottleneck in the post-genomic sciences. Typical experiments rely on varying selected parameters through repeated rounds of trial-and-error optimisation. To rationalise this, several groups have recently adopted the 'design of experiments' (DoE) approach frequently used in industry. Studies have focused on parameters such as medium composition, nutrient feed rates and induction of expression in shake flasks or bioreactors, as well as oxygen transfer rates in micro-well plates. In this study we wanted to generate a predictive model that described small-scale screens and to test its scalability to bioreactors.

Results

Here we demonstrate how the use of a DoE approach in a multi-well mini-bioreactor permitted the rapid establishment of high yielding production phase conditions that could be transferred to a 7 L bioreactor. Using green fluorescent protein secreted from Pichia pastoris, we derived a predictive model of protein yield as a function of the three most commonly-varied process parameters: temperature, pH and the percentage of dissolved oxygen in the culture medium. Importantly, when yield was normalised to culture volume and density, the model was scalable from mL to L working volumes. By increasing pre-induction biomass accumulation, model-predicted yields were further improved. Yield improvement was most significant, however, on varying the fed-batch induction regime to minimise methanol accumulation so that the productivity of the culture increased throughout the whole induction period. These findings suggest the importance of matching the rate of protein production with the host metabolism.

Conclusion

We demonstrate how a rational, stepwise approach to recombinant protein production screens can reduce process development time.
The novel RASSF6 and RASSF10 candidate tumour suppressor genes are frequently epigenetically inactivated in childhood leukaemias
Authors: Hesson Luke B , Dunwell Thomas L , Cooper Wendy N , Catchpoole Daniel , Brini Anna T , Chiaramonte Raffaella , Griffiths Mike , Chalmers Andrew D , Maher Eamonn R , Latif Farida
Published: July 2009

Background

The Ras-assocation family (RASSF) of tumour suppressor genes (TSGs) contains 10 members that encode proteins containing Ras-assocation (RA) domains. Several members of the RASSF family are frequently epigenetically inactivated in cancer, however, their role in leukaemia has remained largely uninvestigated. Also, RASSF10 is a predicted gene yet to be experimentally verified. Here we cloned, characterised and demonstrated expression of RASSF10 in normal human bone marrow. We also determined the methylation status of CpG islands associated with RASSF1–10 in a series of childhood acute lymphocytic leukaemias (ALL) and normal blood and bone marrow samples.

Results

COBRA and bisulphite sequencing revealed RASSF6 and RASSF10 were the only RASSF members with a high frequency of leukaemia-specific methylation. RASSF6 was methylated in 94% (48/51) B-ALL and 41% (12/29) T-ALL, whilst RASSF10 was methylated in 16% (8/51) B-ALL and 88% (23/26) T-ALL. RASSF6 and RASSF10 expression inversely correlated with methylation which was restored by treatment with 5-aza-2'deoxycytidine (5azaDC).

Conclusion

This study shows the hypermethylation profile of RASSF genes in leukaemias is distinct from that of solid tumours and represents the first report of inactivation of RASSF6 or RASSF10 in cancer. These data show epigenetic inactivation of the candidate TSGs RASSF6 and RASSF10 is an extremely frequent event in the pathogenesis of childhood leukaemia. This study also warrants further investigation of the newly identified RASSF member RASSF10 and its potential role in leukaemia.