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Functional Data (functional + data)
Terms modified by Functional Data Selected AbstractsIrradiated cultured apoptotic peripheral blood mononuclear cells regenerate infarcted myocardiumEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2009H. J. Ankersmit Abstract Background, Acute myocardial infarction (AMI) is followed by post AMI cardiac remodelling, often leading to congestive heart failure. Homing of c-kit+ endothelial progenitor cells (EPC) has been thought to be the optimal source for regenerating infarcted myocardium. Methods, Immune function of viable peripheral blood mononuclear cells (PBMC) was evaluated after co-culture with irradiated apoptotic PBMC (IA-PBMC) in vitro. Viable PBMC, IA-PBMC and culture supernatants (SN) thereof were obtained after 24 h. Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were utilized to quantify interleukin-8 (IL-8), vascular endothelial growth factor, matrix metalloproteinase-9 (MMP9) in PBMC, SN and SN exposed fibroblasts. Cell suspensions of viable- and IA-PBMC were infused in an experimental rat AMI model. Immunohistological analysis was performed to detect inflammatory and pro-angiogenic cells within 72 h post-infarction. Functional data and determination of infarction size were quantified by echocardiography and Elastica van Gieson staining. Results, The IA-PBMC attenuated immune reactivity and resulted in secretion of pro-angiogenic IL-8 and MMP9 in vitro. Fibroblasts exposed to viable and IA-PBMC derived SN caused RNA increment of IL-8 and MMP9. AMI rats that were infused with IA-PBMC cell suspension evidenced enhanced homing of endothelial progenitor cells within 72 h as compared to control (medium alone, viable-PBMC). Echocardiography showed a significant reduction in infarction size and improvement in post AMI remodelling as evidenced by an attenuated loss of ejection fraction. Conclusion, These data indicate that infusion of IA-PBMC cell suspension in experimental AMI circumvented inflammation, caused preferential homing of regenerative EPC and replaced infarcted myocardium. [source] Reciprocal activating interaction between 6-sulfo LacNAc+ dendritic cells and NK cellsINTERNATIONAL JOURNAL OF CANCER, Issue 2 2009Rebekka Wehner Abstract Dendritic cells (DCs) display an extraordinary capacity to induce T-cell responses providing the opportunity of DC-based cancer vaccination strategies. Additional findings indicate that DCs may also play a crucial role for the activation of natural killer (NK) cells, which are important effectors in innate antitumor immunity. However, studies investigating the interaction between native human DCs and NK cells are limited. Recently, we defined 6-sulfo LacNAc (slan) DCs as a major subpopulation of myeloid human blood DCs, which represent principal producers of the proinflammatory cytokines tumor necrosis factor-, and interleukin (IL)-12. Functional data revealed that slanDCs efficiently induce neoantigen-specific CD4+ T cells and activate tumor-reactive cytotoxic T cells. When evaluating the crosstalk between slanDCs and NK cells in this study, we found that lipopolysaccharide (LPS)-activated slanDCs efficiently enhance NK cell CD69 expression and interferon (IFN)-, secretion. NK cell-mediated tumor-directed cytotoxicity was significantly improved by slanDCs. NK cell activation induced by slanDCs was critically dependent on IL-12. When investigating the impact of NK cells on the immunostimulatory capacity of slanDCs, we observed that they promote DC maturation. In addition, NK cells strongly enhanced the secretion of immunomodulatory IL-12 and reduced the release of immunosuppressive IL-10 by slanDCs. IFN-, and cell-to-cell contact contributed to these effects. Furthermore, data revealed that DC-NK cell crosstalk improves slanDC-mediated differentiation of naïve CD4+ T lymphocytes into IFN-,-producing Th1 cells. In conclusion, we demonstrate a reciprocal activating interaction between slanDCs and NK cells, which may play a pivotal role in the regulation of antitumor immunity. © 2008 Wiley-Liss, Inc. [source] Tumor imaging in small animals with a combined micro-CT/micro-DSA system using iodinated conventional and blood pool contrast agentsCONTRAST MEDIA & MOLECULAR IMAGING, Issue 4 2006Cristian T. Badea Abstract X-ray based micro-computed tomography (CT) and micro-digital subtraction angiography (DSA) are important non-invasive imaging modalities for following tumorogenesis in small animals. To exploit these imaging capabilities further, the two modalities were combined into a single system to provide both morphological and functional data from the same tumor in a single imaging session. The system is described and examples are given of imaging implanted fibrosarcoma tumors in rats using two types of contrast media: (a) a new generation of blood pool contrast agent containing iodine with a concentration of 130,mg/mL (FenestraÔ VC, Alerion Biomedical, San Diego, CA, USA) for micro-CT and (b) a conventional iodinated contrast agent (Isovue®-370,mg/mL iodine, trademark of Bracco Diagnostics, Princeton, NJ, USA) for micro-DSA. With the blood pool contrast agent, the 3D vascular architecture is revealed in exquisite detail at 100,µm resolution. Micro-DSA images, in perfect registration with the 3D micro-CT datasets, provide complementary functional information such as mean transit times and relative blood flow through the tumor. This imaging approach could be used to understand tumor angiogenesis better and be the basis for evaluating anti-angiogenic therapies. Copyright © 2006 John Wiley & Sons Ltd. [source] A peek inside the neurosecretory brain through Orthopedia lensesDEVELOPMENTAL DYNAMICS, Issue 9 2008Luca Del Giacco Abstract The wealth of expression and functional data presented in this overview discloses the homeogene Orthopedia (Otp) as critical for the development of the hypothalamic neuroendocrine system of vertebrates. Specifically, the results depict the up-to-date portrait of the regulation and functions of Otp. The development of neuroendocrine nuclei relies on Otp from fish to mammals, as demonstrated for several peptide and hormone releasing neurons. Additionally, the activity of Otp is essential for the induction of the dopaminergic phenotype in the hypothalamus of vertebrates. Recent insights into the pathways required for Otp regulation have revealed the implication of the main extracellular signals acting during hypothalamic development. Alterations in these pathways are involved in several neuronal disorders, and the resultant downstream misregulation of Otp might impair the development of the hypothalamus, and be therefore responsible for the neuroendocrine dysfunctions that typify these diseases. Developmental Dynamics 237:2295,2303, 2008. © 2008 Wiley-Liss, Inc. [source] Fetal Mouse Imaging Using Echocardiography: A Review of Current TechnologyECHOCARDIOGRAPHY, Issue 10 2006Christopher F. Spurney M.D. Advances in genetic research have led to the need for phenotypic analysis of small animal models. However, often these genetic alterations, especially when affecting the cardiovascular system, can result in fetal or perinatal death. Noninvasive ultrasound imaging is an ideal method for detecting and studying such congenital malformations, as it allows early recognition of abnormalities in the living fetus and the progression of disease can be followed in utero with longitudinal studies. Two platforms for fetal mouse echocardiography exist, the clinical systems with 15-MHz phased array transducers and research systems with 20,55-MHz mechanical transducers. The clinical ultrasound system has limited two-dimensional (2D) resolution (axial resolution of 440 ,m), but the availability of color and spectral Doppler allows quick interrogations of blood flows, facilitating the detection of structural abnormalities. M-mode imaging further provides important functional data, although, the proper imaging planes are often difficult to obtain. In comparison, the research biomicroscope system has significantly improved 2D resolution (axial resolution of 28 ,m). Spectral Doppler imaging is also available, but in the absence of color Doppler, imaging times are increased and the detection of flow abnormalities is more difficult. M-mode imaging is available and equivalent to the clinical ultrasound system. Overall, the research system, given its higher 2D resolution, is best suited for in-depth analysis of mouse fetal cardiovascular structure and function, while the clinical ultrasound systems, equipped with phase array transducers and color Doppler imaging, are ideal for high-throughput fetal cardiovascular screens. [source] Statistics for spatial functional data: some recent contributionsENVIRONMETRICS, Issue 3-4 2010P. Delicado Abstract Functional data analysis (FDA) is a relatively new branch in statistics. Experiments where a complete function is observed for each individual give rise to functional data. In this work we focus on the case of functional data presenting spatial dependence. The three classic types of spatial data structures (geostatistical data, point patterns, and areal data) can be combined with functional data as it is shown in the examples of each situation provided here. We also review some contributions in the literature on spatial functional data. Copyright © 2009 John Wiley & Sons, Ltd. [source] Analysis of air quality monitoring networks by functional clusteringENVIRONMETRICS, Issue 7 2008R. Ignaccolo Abstract Air quality monitoring networks are important tools in management and evaluation of air quality. Classifying monitoring stations via homogeneous clusters allows e dentification of similarities in pollution, of representative sites, and of spatial patterns. Instead of summaries by statistical indicators, we propose to consider the air pollutant concentrations as functional data. We then classify using functional cluster analysis, where Partitioning Around Medoids (PAM) algorithm is embedded. The proposed data analysis approach is applied to the air quality monitoring network in Piemonte (Northern Italy); we consider the three more critical pollutants: NO2, PM10, and O3. Copyright © 2008 John Wiley & Sons, Ltd. [source] Spatio-temporal distribution of cellular retinoid binding protein gene transcripts in the developing and the adult cochlea.EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2000CRBPI-null mutant mice, Morphological, functional consequences in CRABP- Abstract The expression patterns of the mouse cellular retinoid binding protein genes were investigated by in situ hybridization analysis in the inner ear from 10.5 days post coïtum (dpc) up to the adult stage. The cellular retinoic acid binding protein II (CRABPII) and cellular retinol binding protein I (CRBPI) were present in a widespread and abundant pattern in cochlear structures during embryogenesis. Expression of the cellular retinoic acid binding protein I (CRABPI) is restricted during development in Kölliker's organ whilst cellular retinol binding protein II (CRBPII) is only visible after birth with a ubiquitous distribution in most regions of the cochlea including nervous components. No CRABP or CRBP transcripts were observed in the auditory receptors. Morphological observations of CRBPI- and CRABPI/CRABPII-null mutant fetus at 18.5 dpc do not show any structural modification at the level of the organ of Corti. Furthermore, electrophysiological tests performed by measuring distorsion-product otoacoustic emissions and auditory brainstem evoked responses did not present significant alteration of the auditory function for the different types of mutants. The expression of retinoid binding proteins in cochlear structures during embryogenesis could suggest important roles for these proteins during ontogenesis and morphogenesis of the inner ear. Despite these observations, morphological and functional data from mutant mice did not present obvious modifications of the cochlear structures and auditory thresholds. It is therefore unlikely that CRABPs and CRBPI are directly involved in development of the cochlea and hair cell differentiation. [source] ADAPTIONISM,30 YEARS AFTER GOULD AND LEWONTINEVOLUTION, Issue 10 2009Rasmus Nielsen Gould and Lewontin's 30-year-old critique of adaptionism fundamentally changed the discourse of evolutionary biology. However, with the influx of new ideas and scientific traditions from genomics into evolutionary biology, the old adaptionist controversies are being recycled in a new context. The insight gained by evolutionary biologists, that functional differences cannot be equated to adaptive changes, has at times not been appreciated by the genomics community. In this comment, I argue that even in the presence of both functional data and evidence for selection from DNA sequence data, it is still difficult to construct strong arguments in favor of adaptation. However, despite the difficulties in establishing scientific arguments in favor of specific historic evolutionary events, there is still much to learn about evolution from genomic data. [source] Bone morphogenic protein 3 inactivation is an early and frequent event in colorectal cancer developmentGENES, CHROMOSOMES AND CANCER, Issue 6 2008Kim Loh Bone morphogenic proteins (BMPs) are members of the TGFB growth factor superfamily with well-described functions in bone formation. Although disrupted BMP signalling in tumor development has more recently been investigated, a role for BMP3 in colorectal cancer (CRC) has remained largely unexplored. The aim of this study was to investigate BMP3 disruption in CRCs in relation to both the traditional and serrated pathways of tumor progression. BMP3 was down-regulated as assessed by real-time PCR in 50 of 56 primary tumors (89%). Bisulfite sequencing of the putative promoter revealed extensive hypermethylation in the cell line HT29, in which expression could be restored by treatment with a methyltransferase inhibitor. Aberrant hypermethylation was observed in 33/60 (55%) tumors and was highly correlated with microsatellite instability (P < 0.01), the CpG Island Methylator Phenotype (P < 0.01), BRAF oncogene mutation (P < 0.01), and proximal location (P < 0.001). Methylation was also frequently observed in serrated and traditional adenomatous polyps (22/29, 76%). Re-introduction of BMP3 into cell lines revealed marked growth suppression supporting the functional relevance of this alteration in colorectal tumor development. This study provides molecular and functional data supporting the importance of BMP3 silencing as an early and frequent event in colorectal tumors progressing via the serrated and traditional pathways. © 2008 Wiley-Liss, Inc. [source] Functional analysis of mutations in the ATP loop of the Wilson disease copper transporter, ATP7B,HUMAN MUTATION, Issue 5 2010Leiah M. Luoma Abstract Wilson disease (WND) is an autosomal recessive disorder resulting from mutation of ATP7B. Transport of copper by ATP7B from the trans -Golgi of hepatocytes into apical membrane-trafficked vesicles for excretion in the bile is the major means of copper elimination from the body. Although copper is an essential nutrient, homeostasis must be carefully maintained. If homeostasis is disrupted, copper can accumulate within the liver, kidney, cornea, and/or brain. The range of organs affected leads to clinical heterogeneity and difficulty in WND diagnosis. Sequencing of ATP7B is an important adjunct for diagnosis but has led to the discovery of many novel missense variants. Although prediction programs are available, functional characterization is essential for determining the consequence of novel variants. We have tested 12 missense variants localized to the ATP loop of ATP7B and compared three predictive programs (SIFT, PolyPhen, and Align-GVGD). We found p.L1043P, p.G1000R, p.G1101R, p.I1102T, p.V1239G, and p.D1267V deleterious; p.G1176E and p.G1287S intermediate; p.E1173G temperature sensitive; p.T991M and p.I1148T mild; and p.R1228T functioning as wild type. We found that SIFT most often agreed with functional data (92%), compared with PolyPhen (83%) and Align-GVGD (67%). We conclude that variants found to negatively affect function likely contribute to the WND phenotype in patients. Hum Mutat 31:569,577, 2010. © 2010 Wiley-Liss, Inc. [source] Interpreting missense variants: comparing computational methods in human disease genes CDKN2A, MLH1, MSH2, MECP2, and tyrosinase (TYR),,HUMAN MUTATION, Issue 7 2007Philip A. Chan Abstract The human genome contains frequent single-basepair variants that may or may not cause genetic disease. To characterize benign vs. pathogenic missense variants, numerous computational algorithms have been developed based on comparative sequence and/or protein structure analysis. We compared computational methods that use evolutionary conservation alone, amino acid (AA) change alone, and a combination of conservation and AA change in predicting the consequences of 254 missense variants in the CDKN2A (n = 92), MLH1 (n = 28), MSH2 (n = 14), MECP2 (n = 30), and tyrosinase (TYR) (n = 90) genes. Variants were validated as either neutral or deleterious by curated locus-specific mutation databases and published functional data. All methods that use evolutionary sequence analysis have comparable overall prediction accuracy (72.9,82.0%). Mutations at codons where the AA is absolutely conserved over a sufficient evolutionary distance (about one-third of variants) had a 91.6 to 96.8% likelihood of being deleterious. Three algorithms (SIFT, PolyPhen, and A-GVGD) that differentiate one variant from another at a given codon did not significantly improve predictive value over conservation score alone using the BLOSUM62 matrix. However, when all four methods were in agreement (62.7% of variants), predictive value improved to 88.1%. These results confirm a high predictive value for methods that use evolutionary sequence conservation, with or without considering protein structural change, to predict the clinical consequences of missense variants. The methods can be generalized across genes that cause different types of genetic disease. The results support the clinical use of computational methods as one tool to help interpret missense variants in genes associated with human genetic disease. Hum Mutat 28(7), 683,693, 2007. Published 2007 Wiley-Liss, Inc. [source] Loss of the actin regulator HSPC300 results in clear cell renal cell carcinoma protection in Von Hippel-Lindau patients,,HUMAN MUTATION, Issue 6 2007Alberto Cascón Abstract Clear cell renal cell carcinoma (ccRCC) is the most common malignant neoplasm of the kidney. The majority of hereditary and sporadic ccRCC cases are associated with germline and somatic mutations in the Von Hippel-Lindau gene (VHL), respectively. Gross deletions at the VHL locus can result either in ccRCC or in a mild clinical phenotype, with the absence of ccRCC development. Our goal in this study was to identify the molecular basis responsible for these differences in the clinical behavior in order to predict patients' phenotype. Using multiplex ligation-dependent amplification (MLPA), we identified and characterized gross VHL deletions in Spanish VHL families. A candidate gene related to this clinical association, HSPC300, was identified and depleted by RNA interference. It was possible to narrow the susceptibility region related to the mild clinical phenotype down to ,14,kb that included HSPC300 (C3orf10), a regulator of actin dynamics and cytoskeleton organization. Whereas 9 out of 10 families with ccRCC retained HSPC300 in the germline, loss of the HSPC300 locus was associated with mild clinical presentation of the disease in 6 out of 8 families. In fact, genetic depletion of HSPC300 resulted in cytoskeleton abnormalities and cytokinesis arrest in several tumor cell lines including ccRCC cells, suggesting that tumor cell proliferation was compromised in the absence of HSPC300. These clinical and functional data indicate a relevant function of HSPC300 in tumor cell progression, and suggest future therapeutic strategies based upon the inhibition of HSPC300 in renal cell carcinoma and possibly on other cancers. Hum Mutat 28(6), 613,621, 2007. © 2007 Wiley-Liss, Inc. [source] Central and peripheral autoantigen presentation in immune toleranceIMMUNOLOGY, Issue 2 2004Alberto Pugliese Summary Recent studies in both humans and experimental rodent models provide new insight into key mechanisms regulating tolerance to self-molecules. These recent advances are bringing about a paradigm shift in our views about tolerance to self-molecules with tissue-restricted expression. There is, indeed, mounting evidence that selected antigen-presenting cells (APCs) have the ability to synthesize and express self-molecules, and that such expression is critical for self-tolerance. Insulin is a key hormone produced exclusively by pancreatic ,-cells and a critical autoantigen in type 1 diabetes. It provides an excellent example of a molecule with tissue-restricted expression that is expressed ectopically by APCs. The fact that APCs expressing insulin have been demonstrated in both thymus and peripheral lymphoid tissues suggests that they may play a role in insulin presentation in both the central and peripheral immune system. Experimental mice, in which insulin expression was altered, provide functional data that help to dissect the role of insulin presentation by APCs of the immune system. This review addresses recent literature and emerging concepts about the expression of self-molecules in the thymus and peripheral lymphoid tissues and its relation to self-tolerance. [source] Dynamic T1-weighted monitoring of vascularization in human carcinoma heterotransplants by magnetic resonance imaging,INTERNATIONAL JOURNAL OF CANCER, Issue 1 2003Fabian Kiessling Abstract Studies on tumor angiogenesis and antiangiogenic therapies are commonly performed with tumor heterotransplants in nude mice. To monitor therapeutic effects, improved noninvasive analyses of functional data are required, in addition to the assessment of tumor volume and histology. Here, we report on sequential monitoring of vascularization of human squamous cell carcinomas growing as heterotransplants in nude mice using MRI. Using a custom-developed animal coil in a conventional whole-body 1.5 T MRI scanner, dynamic T1w sequences were recorded after i.v. injection of Gd-DTPA in tumors grown for 17, 21, 25, 29 and 33 days. Amplitude and the exchange rate constant (kep) were calculated according to a 2-compartment model, discriminating intravascular and interstitial spaces, and correlated with tumor size and histology. High-resolution imaging of small heterotransplants from 100 to 1,000 mm3 was achieved, clearly discriminating vital and necrotic areas. Preceding the development of necroses, which were hyperintense in T2w images and confirmed with histology, a local decrease of amplitude and kep values was observed. Significantly higher amplitudes were found in tumor periphery than in central parts, correlating well with the vascular pattern obtained by immunocytochemistry. Tumor size correlated negatively with amplitude, probably as a result of increasing necrotic areas, whereas the reason for the observed increase of kep value with tumor size remains unclear. These data demonstrate that dynamic MRI is an excellent method for noninvasive assessment of tumor vascularization in small animals using a clinical whole-body scanner with little technical modifications. This technique provides functional data characterizing essential features of tumor biology and is thus appropriate for monitoring antiangiogenic therapies. © 2002 Wiley-Liss, Inc. [source] Genetic mapping of dominant white (W), a homozygous lethal condition in the horse (Equus caballus)JOURNAL OF ANIMAL BREEDING AND GENETICS, Issue 6 2004C. Mau Summary Dominant white coat colour (W) is a depigmentation syndrome, known in miscellaneous species. When homozygous in the horse (similar in mice), the mutation responsible for the white phenotype is lethal in a very early stage of gestation. It seems, that the action of the dominant white allele is not always fully penetrant, resulting occasionally in spotted look alike offspring. These horses resemble a coat colour pattern known as sabino spotting. So far, it is not known whether dominant white (W) and sabino spotting (S) share a common genetic background. In this study, a pedigree consisting of 87 horses segregating for dominant white (W) was used to genetically localize the horse (W)-locus. Microsatellite ASB23 was found linked to (W), which allowed us to map dominant white to a region on horse chromosome 3q22. Tyrosine kinase receptor (KIT) was previously mapped to this same chromosome region (3q21,22). KIT and its ligand (KITLG) are responsible for the normal function of melanogenesis, haematopoiesis and gametogenesis. So far, sequence analysis of different KIT gene fragments did not lead to new polymorphisms, except for a SNP detected in KIT intron 3 (KITSNPIn3). Additional microsatellites from ECA3q (TKY353 and LEX7), together with KITSNPIn3 allowed us to state more precisely the (W)-mutation. The positional results and comparative functional data strongly suggest that KIT encodes for the horse (W)-locus. Zusammenfassung Die dominant weisse Fellfarbe (W) ist eine Form der Depigmentierung, die bei vielen Spezies auftritt. Beim Pferd wirkt die Mutation für Dominant Weiss (W) in homozygoter Form (analog zur Maus), bereits in einem sehr frühen Stadium der Trächtigkeit letal. Es scheint, dass die Wirkung des dominant weissen Allels nicht immer mit vollständiger Penetranz erfolgt. Dies führt gelegentlich zu Nachkommen mit einer Art Schecken-Fellzeichnung. Solche Pferde sind phänotypisch mit den sogenannten ,,Sabino-Schecken,, vergleichbar. Es ist bis jetzt nicht bekannt ob Dominant Weiss (W) und Sabino-Scheckung (S) einen gemeinsamen genetischen Hintergrund besitzen. Mittels eines Pedigrees aus 87 Pferden, in dem Dominant Weiss (W) segregiert, konnte in der vorliegenden Studie der equine (W)-Locus genetisch lokalisiert werden. Der Mikrosatellit ASB23 erwies sich als gekoppelt mit (W) und ermöglichte die Zuweisung des (W)-Locus auf eine Region von Chromosom ECA 3q22. Das Gen für den Tyrosinkinaserezeptor (KIT) liegt ebenfalls in dieser Chromosomenregion (3q21,22). Das KIT -Gen ist zusammen mit dem KIT -Liganden (KITLG) verantwortlich für einen normal funktionierenden Ablauf der Melanogenese, Hämatopoese und Gametogenese. Die direkte Sequenzierung von KIT -Genfragmenten führte bis jetzt zu keinen neuen Polymorphismen, ausser einem SNP in KIT Intron 3 (KITSNPIn3). Mittels weiterer Mikrosatelliten von ECA3q (TKY353 and LEX7) sowie KITSNPIn3 gelang es, die (W)-Mutation genauer zu positionieren. Die vorliegenden Lokalisierungsresultate und vergleichende funktionelle Erkenntnisse deuten stark darauf hin, dass KIT für den Pferde (W)-Locus kodiert. [source] Modelling near-infrared signals for on-line monitoring in cheese manufactureJOURNAL OF CHEMOMETRICS, Issue 2 2002B. J. A. Mertens Abstract This paper considers the analysis of a continuously monitored near-infrared reflectance signal at a single wavelength for the calibration of a process parameter in an application to food engineering for quality control. We describe how we may summarize the information in the observed signals by postulating an explicit statistical model on the signal. An exploratory data analysis may then be carried out on the profile summaries to evaluate whether and how the functional data provide information on the parameter which we would like to calibrate. From a conceptual point of view, such an approach is not dissimilar to principal component regression methods which use an intermediate decomposition through which information is summarised for calibration of a response. The paper demonstrates how the approach leads to important insights into the manner in which the functional data provide the required information on the desired outcome variable, in the context of the practical application in quality control which is discussed and by using a designed experiment. Calculations are implemented through the Gibbs sampler. Calibration of the prediction equation takes place through meta-analysis of the summarized profile data in order to take the uncertainty inherent in the summaries into account. Copyright © 2002 John Wiley & Sons, Ltd. [source] Language dominance assessment by means of fMRI: Contributions from task design, performance, and stimulus modalityJOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 5 2001Margret Hund-Georgiadis MD Abstract We investigated the influence of different task demands, task designs, and presentation modalities on the functional MRI activation patterns during a language lateralization task in a group of 14 right-handed control subjects. A word classification task was presented as target task appropriate to evoke language-related activation in the inferior frontal gyrus (IFG). The choice of the contrasting baseline task was demonstrated to have a major impact on the functional outcome: While a fixation baseline elicited activations in the inferior frontal gyrus of both hemispheres, a nonsemantic perceptual control task helped to isolate the relevant target task of word classification. The modality of stimulus presentation did not influence the functional data: Auditory and visual presentation modes broadly evoked activations in similar brain regions during word classification. Minor differences in task performance and the side of the responding hand did not interfere with the functional activation patterns of the target task. On the basis of our results, a protocol of functional lateralization in the inferior frontal gyrus is suggested. J. Magn. Reson. Imaging 2001;13:668,675. © 2001 Wiley-Liss, Inc. [source] A possible molecular mechanism of hanatoxin binding-modified gating in voltage-gated K+ -channelsJOURNAL OF MOLECULAR RECOGNITION, Issue 6 2003Kuo-Long Lou Abstract While S4 is known as the voltage sensor in voltage-gated potassium channels, the carboxyl terminus of S3 (S3C) is of particular interest concerning the site for gating modifier toxins like hanatoxin. The thus derived helical secondary structural arrangement for S3C, as well as its surrounding environment, has since been intensively and vigorously debated. Our previous structural analysis based on molecular simulation has provided sufficient information to describe reasonable docking conformation and further experimental designs (Lou et al., 2002. J. Mol. Recognit. 15: 175,179). However, if one only relies on such information, more advanced structure,functional interpretations for the roles S3C may play in the modification of gating behavior upon toxin binding will remain unknown. In order to have better understanding of the molecular details regarding this issue, we have performed the docking simulation with the S3C sequence from the hanatoxin-insensitive K+ -channel, shaker, and analyzed the conformational changes resulting from such docking. Compared with other functional data from previous studies with respect to the proximity of the S3,S4 linker region, we suggested a significant movement of drk1 S3C, but not shaker S3C, in the direction presumably towards S4, which was comprehended as a possible factor interfering with S4 translocation during drk1 gating in the presence of toxin. In combination with the discussions for structural roles of the length of the S3,S4 linker, a possible molecular mechanism to illustrate the hanatoxin binding-modified gating is proposed. Copyright © 2003 John Wiley & Sons, Ltd. [source] Neuroendocrinological and Molecular Aspects of Insect ReproductionJOURNAL OF NEUROENDOCRINOLOGY, Issue 8 2004G. Simonet Abstract This review summarizes recent advances and novel concepts in the area of insect reproductive neuroendocrinology. The role of ,classic' hormones, such as ecdysteroids and juvenoids, to control reproduction is well documented in a large variety of insect species. In adult gonads, ecdysteroids appear to induce a cascade of transcription factors, many of which also occur during the larval molting response. Recent molecular and functional data have created opportunities to study an additional level of regulation, that of neuropeptides, growth factors and their respective receptors. As a result, many homologs of factors playing a role in vertebrate reproductive physiology have been discovered in insects. This review highlights several neuropeptides controlling the biosynthesis and release of the ,classic' insect hormones, as well as various peptides and biogenic amines that regulate behavioural aspects of the reproduction process. In addition, hormone metabolizing enzymes and second messenger pathways are discussed with respect to their role in reproductive tissues. Finally, we speculate on future prospects for insect neuroendocrinological research as a consequence of the recent ,Genomics Revolution'. [source] Imaging of Language-Related Brain Regions in Detoxified AlcoholicsALCOHOLISM, Issue 6 2009Sandra Chanraud-Guillermo Background:, Neuroimaging studies showed clear evidence of alcoholism-related damage to the frontal lobes and cerebellum. Although these regions have been involved in language processing, language skills are relatively spared in alcoholics. Here, we aimed at identifying neural substrates associated with the preserved mechanisms of language processing in alcoholics. We hypothesized that alcoholics would show a different pattern of neural activity compared with the controls. Methods:, Alcoholic and nonalcoholic subjects performed an auditory language task while receiving a functional magnetic resonance imaging (fMRI) scan in a 1.5 T magnet. This task has been previously shown to solicit the comprehension processing in healthy controls, with reliable fMRI response in the left frontal and temporal/parietal lobes. Results:, Behavioral results showed comparable performance (error rates, response time) between the alcoholics and the matched controls. However, analysis of the functional data revealed that the alcoholics exhibited greater fMRI response in the left middle frontal gyrus (pars triangularis), the right superior frontal gyrus, and the cerebellar vermis relative to the controls. Conclusions:, These findings suggest that frontocerebellar neural activity, supporting the comprehension processing of the auditory language task, may require compensatory mechanisms in alcoholics in order to maintain the same level of performance as the controls. [source] Detecting changes in the mean of functional observationsJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES B (STATISTICAL METHODOLOGY), Issue 5 2009István Berkes Summary., Principal component analysis has become a fundamental tool of functional data analysis. It represents the functional data as Xi(t)=,(t)+,1,l<,,i, l+ vl(t), where , is the common mean, vl are the eigenfunctions of the covariance operator and the ,i, l are the scores. Inferential procedures assume that the mean function ,(t) is the same for all values of i. If, in fact, the observations do not come from one population, but rather their mean changes at some point(s), the results of principal component analysis are confounded by the change(s). It is therefore important to develop a methodology to test the assumption of a common functional mean. We develop such a test using quantities which can be readily computed in the R package fda. The null distribution of the test statistic is asymptotically pivotal with a well-known asymptotic distribution. The asymptotic test has excellent finite sample performance. Its application is illustrated on temperature data from England. [source] Hybrid Dirichlet mixture models for functional dataJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES B (STATISTICAL METHODOLOGY), Issue 4 2009Sonia Petrone Summary., In functional data analysis, curves or surfaces are observed, up to measurement error, at a finite set of locations, for, say, a sample of n individuals. Often, the curves are homogeneous, except perhaps for individual-specific regions that provide heterogeneous behaviour (e.g. ,damaged' areas of irregular shape on an otherwise smooth surface). Motivated by applications with functional data of this nature, we propose a Bayesian mixture model, with the aim of dimension reduction, by representing the sample of n curves through a smaller set of canonical curves. We propose a novel prior on the space of probability measures for a random curve which extends the popular Dirichlet priors by allowing local clustering: non-homogeneous portions of a curve can be allocated to different clusters and the n individual curves can be represented as recombinations (hybrids) of a few canonical curves. More precisely, the prior proposed envisions a conceptual hidden factor with k -levels that acts locally on each curve. We discuss several models incorporating this prior and illustrate its performance with simulated and real data sets. We examine theoretical properties of the proposed finite hybrid Dirichlet mixtures, specifically, their behaviour as the number of the mixture components goes to , and their connection with Dirichlet process mixtures. [source] Wavelet-based functional mixed modelsJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES B (STATISTICAL METHODOLOGY), Issue 2 2006Jeffrey S. Morris Summary., Increasingly, scientific studies yield functional data, in which the ideal units of observation are curves and the observed data consist of sets of curves that are sampled on a fine grid. We present new methodology that generalizes the linear mixed model to the functional mixed model framework, with model fitting done by using a Bayesian wavelet-based approach. This method is flexible, allowing functions of arbitrary form and the full range of fixed effects structures and between-curve covariance structures that are available in the mixed model framework. It yields nonparametric estimates of the fixed and random-effects functions as well as the various between-curve and within-curve covariance matrices. The functional fixed effects are adaptively regularized as a result of the non-linear shrinkage prior that is imposed on the fixed effects' wavelet coefficients, and the random-effect functions experience a form of adaptive regularization because of the separately estimated variance components for each wavelet coefficient. Because we have posterior samples for all model quantities, we can perform pointwise or joint Bayesian inference or prediction on the quantities of the model. The adaptiveness of the method makes it especially appropriate for modelling irregular functional data that are characterized by numerous local features like peaks. [source] Penalized spline models for functional principal component analysisJOURNAL OF THE ROYAL STATISTICAL SOCIETY: SERIES B (STATISTICAL METHODOLOGY), Issue 1 2006Fang Yao Summary., We propose an iterative estimation procedure for performing functional principal component analysis. The procedure aims at functional or longitudinal data where the repeated measurements from the same subject are correlated. An increasingly popular smoothing approach, penalized spline regression, is used to represent the mean function. This allows straightforward incorporation of covariates and simple implementation of approximate inference procedures for coefficients. For the handling of the within-subject correlation, we develop an iterative procedure which reduces the dependence between the repeated measurements that are made for the same subject. The resulting data after iteration are theoretically shown to be asymptotically equivalent (in probability) to a set of independent data. This suggests that the general theory of penalized spline regression that has been developed for independent data can also be applied to functional data. The effectiveness of the proposed procedure is demonstrated via a simulation study and an application to yeast cell cycle gene expression data. [source] Substitutes for grazing in semi-natural grasslands , do mowing or mulching represent valuable alternatives to maintain vegetation structure?JOURNAL OF VEGETATION SCIENCE, Issue 6 2009Christine Römermann Abstract Question: Which management treatments are suitable to replace historically applied grazing regimes? How and why does vegetation structure change following changes in management? Location: Semi-natural calcareous dry grasslands in southwest Germany. Methods: We analysed changes in floristic and functional composition induced by different management treatments (grazing, mowing, mulching, succession) in long-term experimental sites. First, floristic and functional distances between the initial conditions and the following years were determined. Second, we used RLQ analyses to include data on abiotic conditions, vegetation composition and functional traits in one common analysis. Finally, we applied cluster analyses on RLQ species scores to deduce functional groups. Results: In contrast to the historical management regime of grazing, all alternative management treatments led to changes in floristic and functional composition, depending on their intensity with respect to biomass removal. The distance analyses showed that mulching twice per year and mowing did not lead to strong changes in floristic or functional composition. However, RLQ analysis clearly provided evidence that only the grazed sites are in equilibrium, indicating that vegetation change still goes ahead. Conclusions: The current study clearly shows that RLQ is a powerful tool to elucidate ongoing processes that may remain hidden when separately analysing floristic and functional data. Alternative management treatments are not appropriate to sustain the typical disturbance dynamics of species-rich semi-natural grasslands. The less frequent an alternative management treatment is with respect to biomass removal, the less the floristic and functional structure can be maintained. [source] Substrate specificity of three cytochrome c haem lyase isoenzymes from Wolinella succinogenes: unconventional haem c binding motifs are not sufficient for haem c attachment by NrfI and CcsA1MOLECULAR MICROBIOLOGY, Issue 1 2010Melanie Kern Summary Bacterial c -type cytochrome maturation is dependent on a complex enzymic machinery. The key reaction is catalysed by cytochrome c haem lyase (CCHL) that usually forms two thioether bonds to attach haem b to the cysteine residues of a haem c binding motif (HBM) which is, in most cases, a CX2CH sequence. Here, the HBM specificity of three distinct CCHL isoenzymes (NrfI, CcsA1 and CcsA2) from the Epsilonproteobacterium Wolinella succinogenes was investigated using either W. succinogenes or Escherichia coli as host organism. Several reporter c -type cytochromes were employed including cytochrome c nitrite reductases (NrfA) from E. coli and Campylobacter jejuni that differ in their active-site HBMs (CX2CK or CX2CH). W. succinogenes CcsA2 was found to attach haem to standard CX2CH motifs in various cytochromes whereas other HBMs were not recognized. NrfI was able to attach haem c to the active-site CX2CK motif of both W. succinogenes and E. coli NrfA, but not to NrfA from C. jejuni. Different apo-cytochrome variants carrying the CX15CH motif, assumed to be recognized by CcsA1 during maturation of the octahaem cytochrome MccA, were not processed by CcsA1 in either W. succinogenes or E. coli. It is concluded that the dedicated CCHLs NrfI and CcsA1 attach haem to non-standard HBMs only in the presence of further, as yet uncharacterized structural features. Interestingly, it proved impossible to delete the ccsA2 gene from the W. succinogenes genome, a finding that is discussed in the light of the available genomic, proteomic and functional data on W. succinogenes c -type cytochromes. [source] Low-molecular-weight post-translationally modified microcinsMOLECULAR MICROBIOLOGY, Issue 6 2007Konstantin Severinov Summary Microcins are a class of ribosomally synthesized antibacterial peptides produced by Enterobacteriaceae and active against closely related bacterial species. While some microcins are active as unmodified peptides, others are heavily modified by dedicated maturation enzymes. Low-molecular-weight microcins from the post-translationally modified group target essential molecular machines inside the cells. In this review, available structural and functional data about three such microcins , microcin J25, microcin B17 and microcin C7-C51 , are discussed. While all three low-molecular-weight post-translationally modified microcins are produced by Escherichia coli, inferences based on sequence and structural similarities with peptides encoded or produced by phylogenetically diverse bacteria are made whenever possible to put these compounds into a larger perspective. [source] Motor thalamic circuits in primates with emphasis on the area targeted in treatment of movement disordersMOVEMENT DISORDERS, Issue S3 2002Igor A. Ilinsky MD Abstract The ventral region of the motor thalamus that receives cerebellar afferents has been and still is the target of stereotactic interventions for movement disorders. According to Hassler, this area includes ventro-oralis posterior (Vop) and ventral intermedius (Vim) nuclei, although some investigators believe that Vop is associated with the pallidothalamic pathway. We sought to correlate our experimental data on distribution of nigral, pallidal, and cerebellar afferents to the monkey thalamus with Hassler's motor thalamic parcelations. We concluded that Hassler's parcelations retained their value, although some adjustments were needed to relate them to the current neuroanatomic data; particularly, the cerebellothalamic zone that represents the monkey ventral lateral nucleus (VL) corresponds topographically to Hassler's Vop, Vim, and most of Voi. Electron microscopic tracing studies have shown very complex circuitry in this region of the monkey thalamus, as the cerebellar and cortical afferents innervating it are engaged in complex synapses with thalamocortical projection neurons, and this interaction is strongly modulated by local circuit neurons and the input from the reticular thalamic nucleus, which are both inhibitory and ,-aminobutyric acid (GABA)ergic. Spinothalamic afferents also reach the VL, but this input is less studied in the monkey. The circuitry subserving the activity of thalamocortical projection neurons in the VL should be considered while interpreting the functional data obtained in stereotactic surgery. © 2002 Movement Disorder Society [source] Alternative views of functional protein binding epitopes obtained by combinatorial shotgun scanning mutagenesisPROTEIN SCIENCE, Issue 9 2005Gábor Pál Abstract Combinatorial shotgun scanning mutagenesis was used to analyze two large, related protein binding sites to assess the specificity and importance of individual side chain contributions to binding affinity. The strategy allowed for cost-effective generation of a plethora of functional data. The ease of the technology promoted comprehensive investigations, in which the classic alanine-scanning approach was expanded with two additional strategies, serine- and homolog-scanning. Binding of human growth hormone (hGH) to the hGH receptor served as the model system. The entire high affinity receptor-binding sites (site 1) of wild-type hGH (hGHwt) and of an affinity-improved variant (hGHv) were investigated and the results were compared. The contributions that 35 residue positions make to binding were assessed on each hormone molecule by both serine- and homolog-scanning. The hormone molecules were displayed on the surfaces of bacteriophage, and the 35 positions were randomized simultaneously to allow equal starting frequencies of the wild-type residue and either serine or a homologous mutation in separate libraries. Functional selections for binding to the hGH receptor shifted the relative wild-type/mutant frequencies at each position to an extent characteristic of the functional importance of the side chain. Functional epitope maps were created and compared to previous maps obtained by alanine-scanning. Comparisons between the different scans provide insights into the affinity maturation process that produced hGHv. The serine and homolog-scanning results expand upon and complement the alanine-scanning results and provide additional data on the robustness of the high affinity receptor-binding site of hGH. [source] | ||||||||||||||||||||||||||||||||||