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Intensive Research (intensive + research)
Selected AbstractsFunctional and molecular MR imaging of angiogenesis: Seeing the target, seeing it workJOURNAL OF CELLULAR BIOCHEMISTRY, Issue S39 2002Michal NeemanArticle first published online: 16 JAN 200 Abstract Intensive research over the last years led to the discovery of multiple molecular pathways and intricate regulatory network controlling the growth and regression of blood vessels in general and angiogenesis in particular. The difficulties in elucidation of the regulation of angiogenesis, stems from the inherent complexity due to participation of many cell types, under a dominant impact of physiological and environmental effects of flow, perfusion, and oxygenation. Major advances were achieved with the use of sophisticated transgenic mice models engineered so as to provide spatially and temporally controlled expression of specific factors alone or in combination. In vivo analysis of these models frequently requires the use of non-invasive imaging modalities for measurement of functional parameters of the vasculature along with dynamic molecular information. Optical methods are extensively applied for the study of angiogenesis [Brown et al., 2001] but provide very limited tissue penetration. MRI offers the advantage of being non-invasive with uniform and relatively high spatial resolution for deep tissues. Multiple MRI approaches for monitoring angiogenesis were developed over the last years, each looking at a particular step in the process. The aim of this paper is to analyze the clinical, pharmaceutical, and biological needs for imaging of angiogenesis, and to critically evaluate the strengths and weaknesses of functional and molecular imaging for monitoring angiogenesis. The inherent problem of validation of different measures of angiogenesis, and the advantages and limitations associated with application of MRI based methods, as surrogates for other measurements of angiogenesis will be discussed. The terms molecular imaging and functional imaging are frequently loosely defined with a significant overlap between the two. For the sake of this paper we will apply a narrower definition of both terms, where molecular imaging will apply to methods directed towards detection of specific biological molecules that participate directly in (regulation of) a physiological process; while functional imaging will be used to describe those methods that aim to detect the physiological response to a defined (molecular) stimulus. J. Cell. Biochem. Suppl. 39: 11,17, 2002. © 2002 Wiley-Liss, Inc. [source] New Pharmacological Strategies for the Treatment of Atrial FibrillationANNALS OF NONINVASIVE ELECTROCARDIOLOGY, Issue 3 2009Alexander Burashnikov Ph.D. Atrial fibrillation (AF) is a growing clinical problem, increasing in prevalence as the population of the United States and countries around the world ages. Intensive research aimed at improving prevention, diagnosis, and treatment of AF is ongoing. Although the use and efficacy of catheter ablation-based approaches in AF treatment have increased significantly in the last decade, pharmacological agents remain the first-line therapy for rhythm management of AF. Currently available anti-AF agents are generally only moderately effective and associated with extracardiac toxicity and/or a risk for development of life-threatening ventricular arrhythmias. Included among current investigational strategies for improving the effectiveness and safety of anti-AF drugs is the development of (1) Agents that produce atrial-specific or predominant inhibition of IKur, IK-ACh, or INa; (2) "Upstream therapies" that effect nonion channel targets that reduce atrial structural remodeling, hypertrophy, dilatation, inflammation, oxidative injury, etc; (3) Derivatives of "old" anti-AF drugs with an improved safety pharmacological profile; and (4) Gap junction therapy aimed at improving conduction without affecting sodium channels. This review focuses on new pharmacological approaches under investigation for the treatment of AF. [source] Research into the glomerular podocyte,is it relevant to diabetic nephropathy?DIABETIC MEDICINE, Issue 7 2006K. E. White Abstract The cause of proteinuria in renal disease is the subject of intensive research and, latterly, the podocyte, a specialized epithelial cell of the kidney glomerulus, has been the focus of much of this endeavour. It is a complex cell with functions and structural features that have an important role in the development of proteinuria. This review explores some of the characteristics of the podocyte and how abnormalities of its structure and function may have particular relevance to the development and progression of clinical diabetic nephropathy. [source] Trade Balance and Exchange Rate: Unit Roots, Co-integration and Long Memory in the US and the UKECONOMIC NOTES, Issue 1 2008Luis A. Gil-Alana This paper deals with the relationship between the balance of trade and the exchange rate in the US/UK case. Many authors have studied this issue for many countries, but despite the intensive research, there is still no agreement about the effectiveness of currency devaluation to increase a country's balance of trade. We first analyse the relationship between the two variables using unit roots and co-integration methods, and the results are ambiguous. We try a new approach based on fractional integration. The unit root hypothesis is rejected in case of the trade balance in favour of smaller orders of integration, while this hypothesis is not rejected for the exchange rate. Thus, the two series do not possess the same order of integration. We sort this problem out by taking the exchange rate as an exogenous variable, and including it in a regression model where the residuals might follow a fractionally integrated model. [source] Whole body extract of Mediterranean fruit fly males elicits high attraction in virgin femalesENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 1 2008Vassilis G. Mavraganis Abstract The search for effective female attractants emanating from the host or body of fruit flies has been an area of intensive research for over three decades. In the present study, bodies of male Mediterranean fruit flies, Ceratitis capitata (Wiedemann) (Diptera: Tephritidae), were extracted with diethyl ether or methanol and subjected to gas chromatography,mass spectrometry. Analysis revealed substantial qualitative and quantitative differences between males from a laboratory culture and wild males captured alive in an orchard. Most notably, the hydrocarbon sesquiterpene (±)-,-copaene, which is known to be involved in the sexual behaviour of the species, was found in substantial amounts in wild males, but was not detected in laboratory males. In laboratory tests, 15 laboratory or wild male equivalents of diethyl ether extracts or combined diethyl ether and methanol extracts, or, to a lesser extent, methanol extracts alone, were found to attract virgin females. In a citrus orchard, traps baited with combined diethyl ether and methanol extracts of wild males attracted significantly more virgin females than traps baited with various doses of pyranone or blends of other compounds identified in the extracts or reported in the literature, such as ethyl acetate, ethyl-(E)-3-octenoate, and 1-pyrroline. Traps baited with blends of compounds, however, displayed substantial attractiveness compared to control (non-baited) traps. These results are important for better understanding the mating system of C. capitata as well as for further improving existing monitoring and control systems. [source] Development of heterodont dentition in house shrew (Suncus murinus)EUROPEAN JOURNAL OF ORAL SCIENCES, Issue 6 2007Atsushi Yamanaka Mammalian heterodont dentition comprises incisors, canines, premolars, and molars. Although there has been intensive research, the patterning of these specific tooth types has not yet been elucidated. In order for the gene expression data to be linked with tooth type determination, it is first necessary to determine precisely the incisor-, canine-, premolar-, and molar-forming regions in the jaw primordia. To accomplish this, we studied dentition development in the house shrew (Suncus murinus), which has retained all the tooth types, using three-dimensional reconstructions from serial histological sections and the Sonic hedgehog (Shh) expression patterns. Before the appearance of morphological signs of odontogenesis, Shh expression localized to the presumptive tooth-forming regions, in which the mesial and distal expression domains corresponded to the incisor- and premolar-forming regions, respectively. The upper incisor region was found to extend across the boundary between the frontonasal and the maxillary processes. The canine-forming regions later appeared in the intermediate portions of the maxillary and the mandibular processes. The molar-forming regions later appeared distal to the initially demarcated tooth-forming regions by secondary extension of the distal ends. The demarcation visualized by the Shh expression pattern in the jaw primordia of the house shrew probably represents the basic developmental pattern of mammalian heterodont dentition. [source] Boundary characteristics in Heavily Deformed Metals,ADVANCED ENGINEERING MATERIALS, Issue 5 2003G. Winther Abstract The potential of creating nanostructured metals by plastic deformation to very high strains is currently the subject of intensive research. An important part of this research concerns evolution of the characteristics of deformation induced boundaries, in particular boundary spacing and boundary misorientation. The aim of this paper is to give an overview of the present understanding of the relations between these characteristics, the microscopic deformation mechanisms and the macroscopic deformation mode. [source] Virtual Servants: Stereotyping Female Front-Office Employees on the InternetGENDER, WORK & ORGANISATION, Issue 5 2005Eva Gustavsson This article focuses on the service providers of the future: virtual assistants on the Internet. Recent technological developments, supported by intensive research on artificial intelligence, have enabled corporations to construct ,virtual employees' who can interact with their online customers. The number of virtual assistants on the Internet continues to grow and most of these new service providers are human-like and female. In this article I profile virtual employees on the Internet , who they are, what they do and how they present themselves. I demonstrate that the Internet suffers from the same gender stereotyping characteristic of customer services in general and that the unreflective choice of female images is, at the minimum, a symbolic reinforcement of the real circumstances of gender divisions in customer service. [source] Does compression affect image retrieval performance?INTERNATIONAL JOURNAL OF IMAGING SYSTEMS AND TECHNOLOGY, Issue 2-3 2008Gerald Schaefer Abstract Image retrieval and image compression are both fields of intensive research. As lossy image compression degrades the visual quality of images and hence changes the actual pixel values of an image, low level image retrieval descriptors which are based on statistical properties of pixel values will change, too. In this article we investigate how image compression affects the performance of low-level colour descriptors. Several image retrieval algorithms are evaluated on a speciated image database compressed at different image quality levels. Extensive experiments reveal that while distribution-based colour descriptors are fairly stable with respect to image compression a drop in retrieval performance can nevertheless be observed for JPEG compressed images. On the other hand, after application of JPEG2000 compression only a negligible performance drop is observed even at high compression ratios. © 2008 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 18, 101,112, 2008 [source] Evaluation of Drought-Related Traits and Screening Methods at Different Developmental Stages in Spring BarleyJOURNAL OF AGRONOMY AND CROP SCIENCE, Issue 5 2008F. Szira Abstract Despite intensive research and breeding efforts, the physiological and quantitative genetic bases of drought tolerance are still poorly understood. The comparison of results obtained from different sources is also complex, because different testing methods may lead to controversial conclusions. This report discusses various drought stress experiments (hydroponics and in soil) in which the plant tolerance was studied at different developmental stages. Tests were performed in the germination, seedling and adult plant stages on the parental lines of five well-known barley-mapping populations. The results suggest that drought tolerance is a stage-specific trait and changes during the life cycle. The effect of drought stress depended not only on the duration and intensity of water deficiency, but also on the developmental phase in which it began. To induce the same type of stress and to obtain comparable tolerance information from the replications, it is recommended that drought stress should be induced at the same growth stage. Correlations between the traits, commonly associated with improved drought resistance (high relative water content under stress, proline accumulation, osmoregulation) with stress tolerance indexes, are also presented, while the advantages and disadvantages of the most frequently used screening methods are discussed. [source] Long-term RNA interference and its application to hepatitis B virusJOURNAL OF DIGESTIVE DISEASES, Issue 3 2009Jin Shui PAN RNA interference (RNAi) is an ancient defensive mechanism in eukaryotes to control gene expressing and defend their genomes from foreign invaders. It refers to the phenomenon that double-stranded RNA results in the sequence-specific silencing of target gene expression. Although it was documented in a relatively short time ago, intensive research has facilitated making its mechanism clear. Researchers have found that it was a powerful tool for analyzing the functions of genes and treating tumors, infectious diseases and genetic abnormalities that are associated with a dominant gene defect. However, delivery in vivo, low blood stability and poor intracellular uptake present significant challenges for the development of RNAi reagents in clinical use. Thus, long-term inducible RNAi was designed. There are hundreds of millions of hepatitis B virus (HBV) carriers in the world at present, a portion of whom will lose their lives after several years due to chronic complications such as cirrhosis, hepatocellular carcinomas or both. Although a preventive vaccine is now available, the present therapeutic options for chronically infected patients are limited and of low efficiency. Admittedly, to date most RNAi experiments have been done in vitro, but it is hoped that they may be developed into a therapeutic strategy for HBV in the near future. In this article the principles and construction of long-term RNA are discussed. Its therapeutic potentiality and attention to the potential hazards will also outlined. We conclude that this ancient defensive mechanism can be recruited as a powerful weapon in the fight against HBV. [source] Grasping determination experiments within the UJI robotics telelabJOURNAL OF FIELD ROBOTICS (FORMERLY JOURNAL OF ROBOTIC SYSTEMS), Issue 4 2005Raul Marín As a result of new technology becoming available it is increasingly possible to develop more natural human-robot interfaces. In particular, interaction channels based on both voice and synthesis recognition, and combined with other sensors, mainly computer vision, are now implemented in current robots. These capabilities enable a more natural face-to-face dialogue in the human-robot interaction. Currently, they are demonstrating their potential in many service robot applications, such as museums, hospitals, and so on. One area where these new forms of interaction have been extensively tested recently is within the educational robotics context. This article addresses a novel user-interface implemented in such a system developed in our lab, namely "The UJI Robotics Telelab", where the word UJI is the acronym for the name of our University. In order to develop this kind of complex system, several years of intensive research have been necessary in both multimedia tutoring systems and robotics. The principal motive for the project was the experimentation and validation of a complete telelaboratory, including an Internet-based robot system, with off-line and on-line control possibilities, and other different facilities (e.g., multimedia tutorial, chat channel, etc.) aimed at teaching undergraduate students in the robotics subject in our university campus. Finally, taking into account experience gained from using this system for regular undergraduate courses in robotics, new facilities have been implemented, and results showing the user performance, usability, and reliability of this novel contribution are discussed, including its advantages and limitations. © 2005 Wiley Periodicals, Inc. [source] Schmeissneria: An angiosperm from the Early JurassicJOURNAL OF SYSTEMATICS EVOLUTION, Issue 5 2010Xin WANG Abstract, The origin of angiosperms has been a focus of intensive research for a long time. The so-called pre-Cretaceous angiosperms, including Schmeissneria, are usually clouded with doubt. To expel the cloud around the enigmatic Schmeissneria, the syntype and new materials of Schmeissneria collected previously in Germany and recently in China are studied. These materials include female inflorescences and infructescences. The latter are old materials but were under-studied previously. Light microscopy and scanning electron microscope observations indicate that the fruits in these infructescences have in situ seeds enclosed, and that the ovaries are closed before pollination. Thus the plants meet two strict criteria for angiosperms: angiospermy plus angio-ovuly. Placing Schmeissneria in angiosperms will extend the record of angiosperms up to the Early Jurassic, more compatible with many molecular dating conclusions on the age of angiosperms, and demanding a reassessment of the current doctrines on the origin of angiosperms. Although the phylogenetic relationship of Schmeissneria to other angiosperms apparently is still an open question, this study adds to research concerning the origin of angiosperms. [source] Materials in particulate form for tissue engineering.JOURNAL OF TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Issue 2 2007Abstract Materials in particulate form have been the subjects of intensive research in view of their use as drug delivery systems. While within this application there are still issues to be addressed, these systems are now being regarded as having a great potential for tissue engineering applications. Bone repair is a very demanding task, due to the specific characteristics of skeletal tissues, and the design of scaffolds for bone tissue engineering presents several difficulties. Materials in particulate form are now seen as a means of achieving higher control over parameters such as porosity, pore size, surface area and the mechanical properties of the scaffold. These materials also have the potential to incorporate biologically active molecules for release and to serve as carriers for cells. It is believed that the combination of these features would create a more efficient approach towards regeneration. This review focuses on the application of materials in particulate form for bone tissue engineering. A brief overview of bone biology and the healing process is also provided in order to place the application in its broader context. An original compilation of molecules with a documented role in bone tissue biology is listed, as they have the potential to be used in bone tissue engineering strategies. To sum up this review, examples of works addressing the above aspects are presented. Copyright © 2007 John Wiley & Sons, Ltd. [source] Cross-talk between skeletal muscle and adipose tissue: A link with obesity?MEDICINAL RESEARCH REVIEWS, Issue 1 2005Josep M. Argilés Abstract Since the discovery of leptin, the adipocyte and its products have been the subject of intensive research. Thus, it has been demonstrated that adipose tissue plays a central role in energy homeostasis, behaving as an endocrine organ that expresses molecules involved in regulation of metabolism; alterations in the expression or activity of those molecules have a fundamental role in pathologies such as obesity and insulin resistance. However, little is known about the role played by another tissue, skeletal muscle, which may have similar functions regarding metabolism control. Indeed, some molecules expressed in this tissue have recently been shown to modulate adipose metabolism. The present review considers the metabolic interrelationships and cross-talk of signals derived from both skeletal muscle and adipose tissue. It is suggested that cytokines derived from both tissues may have an important role in maintaining an adequate ratio of skeletal muscle to fat and thus may play an important role in the control of body weight. IL-15 (a cytokine highly-expressed in skeletal muscle), TNF-,, and leptin could play a decisive role in the suggested "conversation" between adipose tissue and skeletal muscle. © 2004 Wiley Periodicals, Inc. [source] From fundamental studies of sporulation to applied spore researchMOLECULAR MICROBIOLOGY, Issue 2 2005Imrich Barák Summary Sporulation in the Gram-positive bacterium, Bacillus subtilis, has been used as an excellent model system to study cell differentiation for almost half a century. This research has given us a detailed picture of the genetic, physiological and biochemical mechanisms that allow bacteria to survive harsh environmental conditions by forming highly robust spores. Although many basic aspects of this process are now understood in great detail, including the crystal and NMR structures of some of the key proteins and their complexes, bacterial sporulation still continues to be a highly attractive model for studying various cell processes at a molecular level. There are several reasons for such scientific interest. First, some of the complex steps in sporulation are not fully understood and/or are only described by ,controversial' models. Second, intensive research on unicellular development of a single microorganism, B. subtilis, left us largely unaware of the multitude of diverse sporulation mechanisms in many other Gram-positive endospore and exospore formers. This diversity would likely be increased if we were to include sporulation processes in the Gram-negative spore formers. Spore formers have great potential in applied research. They have been used for many years as biodosimeters and as natural insecticides, exploited in the industrial production of enzymes, antibiotics, used as probiotics and, more, exploited as possible vectors for drug delivery, vaccine antigens and other immunomodulating molecules. This report describes these and other aspects of current fundamental and applied spore research that were presented at European Spores Conference held in Smolenice Castle, Slovakia, June 2004. [source] Gaeumannomyces graminis, the take-all fungus and its relativesMOLECULAR PLANT PATHOLOGY, Issue 4 2004JACQUELINE FREEMAN SUMMARY Take-all, caused by the fungus Gaeumannomyces graminis var. tritici, is the most important root disease of wheat worldwide. Many years of intensive research, reflected by the large volume of literature on take-all, has led to a considerable degree of understanding of many aspects of the disease. However, effective and economic control of the disease remains difficult. The application of molecular techniques to study G. graminis and related fungi has resulted in some significant advances, particularly in the development of improved methods for identification and in elucidating the role of the enzyme avenacinase as a pathogenicity determinant in the closely related oat take-all fungus (G. graminis var. avenae). Some progress in identifying other factors that may be involved in determining host range and pathogenicity has been made, despite the difficulties of performing genetic analyses and the lack of a reliable transformation system. [source] A mathematical and statistical framework for modelling dispersalOIKOS, Issue 6 2007Tord Snäll Mechanistic and phenomenological dispersal modelling of organisms has long been an area of intensive research. Recently, there has been an increased interest in intermediate models between the two. Intermediate models include major mechanisms that affect dispersal, in addition to the dispersal curve of a phenomenological model. Here we review and describe the mathematical and statistical framework for phenomenological dispersal modelling. In the mathematical development we describe modelling of dispersal in two dimensions from a point source, and in one dimension from a line or area source. In the statistical development we describe applicable observation distributions, and the procedures of model fitting, comparison, checking, and prediction. The procedures are also demonstrated using data from dispersal experiments. The data are hierarchically structured, and hence, we fit hierarchical models. The Bayesian modelling approach is applied, which allows us to show the uncertainty in the parameter estimates and in predictions. Finally, we show how to account for the effect of wind speed on the estimates of the dispersal parameters. This serves as an example of how to strengthen the coupling in the modelling between the phenomenon observed in an experiment and the underlying process , something that should be striven for in the statistical modelling of dispersal. [source] Immune mechanisms of resistance to gastrointestinal nematode infections in sheepPARASITE IMMUNOLOGY, Issue 8 2010W. R. HEIN Summary Infections with gastrointestinal nematode parasites are a major problem for the sheep industry in Australia and New Zealand and have been the subject of intensive research to define mechanisms of resistance. The ability to take continuous biopsy samples of infected organs and cannulate both afferent and efferent lymphatics of draining lymph nodes has been particularly useful in illuminating the kinetics of immune responses at the site of infection. Distinct localized immune responses were shown to occur within and between sheep breeds at different sensitization regimes, as well as at different developmental stages of the parasite within the host. Using localized antibodies derived from mucus and lymph nodes, two major antigens have been identified on the infective L3 stage, which may be responsible for inducing protection and have potential as vaccine targets. Recent advances in sheep genomics also offer the potential of gaining further insight into the underlying genetics of resistance to nematode infections. [source] Potential association between endogenous leptin and sympatho-vagal activities in young obese Japanese womenAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 1 2003Tamaki Matsumoto Leptin is an adipocyte-derived hormone that decreases food intake and increases energy expenditure through the activation of the sympathetic nervous system (SNS). Notwithstanding recent intensive research, the underlying physiological mechanism of leptin as well as the etiology of obesity in humans remains elusive. The present study attempted to investigate the potential association between endogenous circulating leptin and sympatho-vagal activities in age- and height-matched obese and nonobese healthy young women. Plasma leptin concentrations were measured by radioimmunoassay. The autonomic nervous system activity was assessed during the resting condition by means of a recently devised power spectral analysis of heart rate variability, which serves to identify three separate frequency components, very low (VLO), low (LO), and high (HI). Plasma leptin concentrations were greater in the obese than in the control group (45.7 ± 5.89 vs. 11.2 ± 1.10 ng · ml,1, P < 0.01). As to the contribution of endogenous leptin to SNS activity, both the ratios of the VLO frequency component reflecting thermoregulatory sympathetic function and the global SNS index [(VLO + LO)/HI] to plasma leptin concentration were markedly reduced in the obese compared to the control group (VLO per leptin: 5.9 ± 1.39 vs. 37.8 ± 8.1 ms2 · ml · ng,1, P < 0.01; SNS index per leptin: 0.04 ± 0.008 vs. 0.33 ± 0.01 ml,,·,ng,1, P < 0.01). Additionally, a nonlinear regression analysis revealed that these ratios exponentially decreased as a function of body fat content (VLO per leptin r2 = 0.57, P < 0.01; SNS index per leptin r2 = 0.53, P < 0.01). Our data suggest that reduced sympathetic responsiveness to endogenous leptin production, implying peripheral leptin resistance, might be a pathophysiological feature of obesity in otherwise healthy young women. The findings regarding the association of leptin, body fat content, and SNS activity further indicate that the 30% of total body fat, which has been used as a criterion of obesity, might be a critical point at which leptin resistance is induced. Am. J. Hum. Biol. 15:8,15, 2003. © 2002 Wiley-Liss, Inc. [source] The effect of drought and heat stress on reproductive processes in cerealsPLANT CELL & ENVIRONMENT, Issue 1 2008BEÁTA BARNABÁS ABSTRACT As the result of intensive research and breeding efforts over the last 20 years, the yield potential and yield quality of cereals have been greatly improved. Nowadays, yield safety has gained more importance because of the forecasted climatic changes. Drought and high temperature are especially considered as key stress factors with high potential impact on crop yield. Yield safety can only be improved if future breeding attempts will be based on the valuable new knowledge acquired on the processes determining plant development and its responses to stress. Plant stress responses are very complex. Interactions between plant structure, function and the environment need to be investigated at various phases of plant development at the organismal, cellular as well as molecular levels in order to obtain a full picture. The results achieved so far in this field indicate that various plant organs, in a definite hierarchy and in interaction with each other, are involved in determining crop yield under stress. Here we attempt to summarize the currently available information on cereal reproduction under drought and heat stress and to give an outlook towards potential strategies to improve yield safety in cereals. [source] Identification and estimation of local average derivatives in non-separable models without monotonicityTHE ECONOMETRICS JOURNAL, Issue 1 2009Stefan Hoderlein Summary, In many structural economic models there are no good arguments for additive separability of the error. Recently, this motivated intensive research on non-separable structures. For instance, in Hoderlein and Mammen (2007) a non-separable model in the single equation case was considered, and it was established that in the absence of the frequently employed monotonicity assumption local average structural derivatives (LASD) are still identified. In this paper, we introduce an estimator for the LASD. The estimator we propose is based on local polynomial fitting of conditional quantiles. We derive its large sample distribution through a Bahadur representation, and give some related results, e.g. about the asymptotic behaviour of the quantile process. Moreover, we generalize the concept of LASD to include endogeneity of regressors and discuss the case of a multivariate dependent variable. We also consider identification of structured non-separable models, including single index and additive models. We discuss specification testing, as well as testing for endogeneity and for the impact of unobserved heterogeneity. We also show that fixed censoring can easily be addressed in this framework. Finally, we apply some of the concepts to demand analysis using British Consumer Data. [source] Neurodevelopmental expression and localization of the cellular prion protein in the central nervous system of the mouseTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 11 2010Stefano Benvegnů Abstract Transmissible spongiform encephalopathies (TSEs) are neurodegenerative disorders caused by PrPSc, or prion, an abnormally folded form of the cellular prion protein (PrPC). The abundant expression of PrPC in the central nervous system (CNS) is a requirement for prion replication, yet despite years of intensive research the physiological function of PrPC still remains unclear. Several routes of investigation point out a potential role for PrPC in axon growth and neuronal development. Thus, we undertook a detailed analysis of the spatial and temporal expression of PrPC during mouse CNS development. Our findings show regional differences of the expression of PrP, with some specific white matter structures showing the earliest and highest expression of PrPC. Indeed, all these regions are part of the thalamolimbic neurocircuitry, suggesting a potential role of PrPC in the development and functioning of this specific brain system. J. Comp. Neurol. 518:1879,1891, 2010. © 2010 Wiley-Liss, Inc. [source] Neurodevelopmental expression and localization of the cellular prion protein in the central nervous system of the mouseTHE JOURNAL OF COMPARATIVE NEUROLOGY, Issue 11 2010Stefano Benvegnů Abstract Transmissible spongiform encephalopathies (TSEs) are neurodegenerative disorders caused by PrPSc, or prion, an abnormally folded form of the cellular prion protein (PrPC). The abundant expression of PrPC in the central nervous system (CNS) is a requirement for prion replication, yet despite years of intensive research the physiological function of PrPC still remains unclear. Several routes of investigation point out a potential role for PrPC in axon growth and neuronal development. Thus, we undertook a detailed analysis of the spatial and temporal expression of PrPC during mouse CNS development. Our findings show regional differences of the expression of PrP, with some specific white matter structures showing the earliest and highest expression of PrPC. Indeed, all these regions are part of the thalamolimbic neurocircuitry, suggesting a potential role of PrPC in the development and functioning of this specific brain system. J. Comp. Neurol. 518:1879,1891, 2010. © 2010 Wiley-Liss, Inc. [source] A Version of the EM Algorithm for Proportional Hazard Model with Random EffectsBIOMETRICAL JOURNAL, Issue 6 2005José Cortińas Abrahantes Abstract Proportional hazard models with multivariate random effects (frailties) acting multiplicatively on the baseline hazard have recently become a topic of an intensive research. One of the main practical problems related to the models is the estimation of parameters. To this aim, several approaches based on the EM algorithm have been proposed. The major difference between these approaches is the method of the computation of conditional expectations required at the E-step. In this paper an alternative implementation of the EM algorithm is proposed, in which the expected values are computed with the use of the Laplace approximation. The method is computationally less demanding than the approaches developed previously. Its performance is assessed based on a simulation study and compared to a non-EM based estimation approach proposed by Ripatti and Palmgren (2000). (© 2005 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim) [source] | ||||||||||||||||||||||||||||