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Sample records for segmental specific dysregulation

  1. Specific mixing facilitates the comparative quantification of phosphorylation sites with significant dysregulations

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    Liu, Jing [Key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic R& A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian 116023 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Xu, Bo [Key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic R& A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian 116023 (China); Liu, Zheyi; Dong, Mingming; Mao, Jiawei; Zhou, Ye; Chen, Jin [Key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic R& A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian 116023 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Wang, Fangjun, E-mail: wangfj@dicp.ac.cn [Key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic R& A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian 116023 (China); Zou, Hanfa [Key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic R& A Center, Dalian Institute of Chemical Physics, Chinese Academy of Sciences (CAS), Dalian 116023 (China)

    2017-01-15

    Mass spectrometry (MS) based quantitative analyses of proteome and proteome post-translational modifications (PTMs) play more and more important roles in biological, pharmaceutical and clinical studies. However, it is still a big challenge to accurately quantify the proteins or proteins PTM sites with extreme relative abundances in comparative protein samples, such as the significantly dysregulated ones. Herein, a novel quantification strategy, Mixing at Specific Ratio (MaSR) before isotope labeling, had been developed to improve the quantification accuracy and coverage of extreme proteins and protein phosphorylation sites. Briefly, the comparative protein samples were firstly mixed together at specific ratios of 9:1 and 1:9 (w/w), followed with mass differentiate light and heavy isotope labeling, respectively. The extreme proteins and protein phosphorylation sites, even if the newly expressed or disappeared ones, could be accurately quantified due to all of the proteins' relative abundances had been adjusted to 2 orders of magnitude (1/9-9) by this strategy. The number of quantified phosphorylation sites with more than 20 folds changes was improved about 10 times in comparative quantification of pervanadate stimulated phosphoproteome of HeLa cells, and 134 newly generated and 21 disappeared phosphorylation sites were solely quantified by the MaSR strategy. The significantly up-regulated phosphorylation sites were mainly involved in the key phosphoproteins regulating the insulin-related pathways, such as PI3K-AKT and RAS-MAPK pathways. Therefore, the MaSR strategy exhibits as a promising way in elucidating the biological processes with significant dysregulations. - Highlights: • All the proteins' relative abundances were adjusted into 2 orders of magnitude (1/9-9). • The quantification accuracy and coverage of extreme proteins and protein phosphorylation sites had been improved. • The newly expressed or disappeared proteins and protein

  2. Preoccupied Attachment and Emotional Dysregulation: Specific Aspects of Borderline Personality Disorder or General Dimensions of Personality Pathology?

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    Scott, Lori N.; Kim, Yookyung; Nolf, Kimberly A.; Hallquist, Michael N.; Wright, Aidan G.C.; Stepp, Stephanie D.; Morse, Jennifer Q.; Pilkonis, Paul A.

    2013-01-01

    Emotional dysregulation and impaired attachment are seen by many clinical researchers as central aspects of borderline personality disorder (BPD). Alternatively, these constructs may represent general impairments in personality that are nonspecific to BPD. Using multitrait-multimethod models, we examined the strength of associations among preoccupied attachment, difficulties with emotion regulation, BPD features, and features of two other personality disorders (i.e., antisocial and avoidant) in a combined psychiatric outpatient and community sample of adults. Results suggested that preoccupied attachment and difficulties with emotion regulation shared strong positive associations with each other and with each of the selected personality disorders. However, preoccupied attachment and emotional dysregulation were more strongly related to BPD features than to features of other personality disorders. Our findings suggest that although impairments in relational and emotional domains may underlie personality pathology in general, preoccupied attachment and emotional dysregulation also have specificity for understanding core difficulties in those with BPD. PMID:23586934

  3. Preoccupied attachment and emotional dysregulation: specific aspects of borderline personality disorder or general dimensions of personality pathology?

    Science.gov (United States)

    Scott, Lori N; Kim, Yookyung; Nolf, Kimberly A; Hallquist, Michael N; Wright, Aidan G C; Stepp, Stephanie D; Morse, Jennifer Q; Pilkonis, Paul A

    2013-08-01

    Emotional dysregulation and impaired attachment are seen by many clinical researchers as central aspects of borderline personality disorder (BPD). Alternatively, these constructs may represent general impairments in personality that are nonspecific to BPD. Using multitraitmultimethod models, the authors examined the strength of associations among preoccupied attachment, difficulties with emotion regulation, BPD features, and features of two other personality disorders (i.e., antisocial and avoidant) in a combined psychiatric outpatient and community sample of adults. Results suggested that preoccupied attachment and difficulties with emotion regulation shared strong positive associations with each other and with each of the selected personality disorders. However, preoccupied attachment and emotional dysregulation were more strongly related to BPD features than to features of other personality disorders. Findings suggest that although impairments in relational and emotional domains may underlie personality pathology in general, preoccupied attachment and emotional dysregulation also have specificity for understanding core difficulties in those with BPD.

  4. Segment-Specific Adhesion as a Driver of Convergent Extension

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    Vroomans, Renske M. A.; Hogeweg, Paulien; ten Tusscher, Kirsten H. W. J.

    2015-01-01

    Convergent extension, the simultaneous extension and narrowing of tissues, is a crucial event in the formation of the main body axis during embryonic development. It involves processes on multiple scales: the sub-cellular, cellular and tissue level, which interact via explicit or intrinsic feedback mechanisms. Computational modelling studies play an important role in unravelling the multiscale feedbacks underlying convergent extension. Convergent extension usually operates in tissue which has been patterned or is currently being patterned into distinct domains of gene expression. How such tissue patterns are maintained during the large scale tissue movements of convergent extension has thus far not been investigated. Intriguingly, experimental data indicate that in certain cases these tissue patterns may drive convergent extension rather than requiring safeguarding against convergent extension. Here we use a 2D Cellular Potts Model (CPM) of a tissue prepatterned into segments, to show that convergent extension tends to disrupt this pre-existing segmental pattern. However, when cells preferentially adhere to cells of the same segment type, segment integrity is maintained without any reduction in tissue extension. Strikingly, we demonstrate that this segment-specific adhesion is by itself sufficient to drive convergent extension. Convergent extension is enhanced when we endow our in silico cells with persistence of motion, which in vivo would naturally follow from cytoskeletal dynamics. Finally, we extend our model to confirm the generality of our results. We demonstrate a similar effect of differential adhesion on convergent extension in tissues that can only extend in a single direction (as often occurs due to the inertia of the head region of the embryo), and in tissues prepatterned into a sequence of domains resulting in two opposing adhesive gradients, rather than alternating segments. PMID:25706823

  5. Memory colour segmentation and classification using class-specific eigenregions

    OpenAIRE

    Fredembach, Clement; Estrada, Francisco; Süsstrunk, Sabine

    2009-01-01

    Memory colours refer to the colour of specific image regions that have the essential attribute of being perceived in a consistent manner by human observers. In colour correction-or rendering-tasks, this consistency implies that they have to be faithfully reproduced; their importance, in that respect, is greater than for other regions in an image. There are various schemes and attributes to detect memory colours, but the preferred method remains to segment the images into meaningful regions, a...

  6. Modelling of subject specific based segmental dynamics of knee joint

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    Nasir, N. H. M.; Ibrahim, B. S. K. K.; Huq, M. S.; Ahmad, M. K. I.

    2017-09-01

    This study determines segmental dynamics parameters based on subject specific method. Five hemiplegic patients participated in the study, two men and three women. Their ages ranged from 50 to 60 years, weights from 60 to 70 kg and heights from 145 to 170 cm. Sample group included patients with different side of stroke. The parameters of the segmental dynamics resembling the knee joint functions measured via measurement of Winter and its model generated via the employment Kane's equation of motion. Inertial parameters in the form of the anthropometry can be identified and measured by employing Standard Human Dimension on the subjects who are in hemiplegia condition. The inertial parameters are the location of centre of mass (COM) at the length of the limb segment, inertia moment around the COM and masses of shank and foot to generate accurate motion equations. This investigation has also managed to dig out a few advantages of employing the table of anthropometry in movement biomechanics of Winter's and Kane's equation of motion. A general procedure is presented to yield accurate measurement of estimation for the inertial parameters for the joint of the knee of certain subjects with stroke history.

  7. Optimal Versus Realized Trajectories of Physiological Dysregulation in Aging and Their Relation to Sex-Specific Mortality Risk

    DEFF Research Database (Denmark)

    Arbeev, Konstantin G; Cohen, Alan A; Arbeeva, Liubov S

    2016-01-01

    dysregulation is related to different aging-related characteristics such as decline in stress resistance and adaptive capacity (which typically are not observed in the data and thus can be analyzed only indirectly), and, ultimately, to estimate how such dynamic relationships increase mortality risk with age. We...... substantial sex differences in these processes, with women becoming dysregulated more quickly but with men showing a much greater sensitivity to dysregulation in terms of mortality risk....

  8. The impact of childhood abuse on inpatient substance users: specific links with risky sex, aggression, and emotion dysregulation.

    Science.gov (United States)

    Banducci, Anne N; Hoffman, Elana M; Lejuez, C W; Koenen, Karestan C

    2014-05-01

    Adults with substance use disorders (SUDs) report a high prevalence of childhood abuse. Research in the general population suggests specific types of abuse lead to particular negative outcomes; it is not known whether this pattern holds for adults with SUDs. We hypothesized that specific types of abuse would be associated with particular behavioral and emotional outcomes among substance users. That is, childhood sexual abuse would be associated with risky sex behaviors, childhood physical abuse with aggression, and childhood emotional abuse with emotion dysregulation. 280 inpatients (M age=43.3; 69.7% male; 88.4% African American) in substance use treatment completed the Childhood Trauma Questionnaire (CTQ), HIV Risk-Taking Behavior Scale, Addiction Severity Index, Difficulties with Emotion Regulation Scale (DERS), Distress Tolerance Scale (DTS), and Affect Intensity and Dimensions of Affiliation Motivation (AIM). Consistent with our hypotheses, the CTQ sexual abuse subscale uniquely predicted exchanging sex for cocaine and heroin, number of arrests for prostitution, engaging in unprotected sex with a casual partner during the prior year, and experiencing low sexual arousal when sober. The physical abuse subscale uniquely predicted number of arrests for assault and weapons offenses. The emotional abuse subscale uniquely predicted the DERS total score, AIM score, and DTS score. Among substance users, different types of abuse are uniquely associated with specific negative effects. Assessment of specific abuse types among substance users may be informative in treatment planning and relapse prevention. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Optimal Dynamic Advertising Strategy Under Age-Specific Market Segmentation

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    Krastev, Vladimir

    2011-12-01

    We consider the model proposed by Faggian and Grosset for determining the advertising efforts and goodwill in the long run of a company under age segmentation of consumers. Reducing this model to optimal control sub problems we find the optimal advertising strategy and goodwill.

  10. Pre-existing neutralizing antibody mitigates B cell dysregulation and enhances the Env-specific antibody response in SHIV-infected rhesus macaques.

    Directory of Open Access Journals (Sweden)

    Juan Pablo Jaworski

    Full Text Available Our central hypothesis is that protection against HIV infection will be powerfully influenced by the magnitude and quality of the B cell response. Although sterilizing immunity, mediated by pre-formed abundant and potent antibodies is the ultimate goal for B cell-targeted HIV vaccine strategies, scenarios that fall short of this may still confer beneficial defenses against viremia and disease progression. We evaluated the impact of sub-sterilizing pre-existing neutralizing antibody on the B cell response to SHIV infection. Adult male rhesus macaques received passive transfer of a sub-sterilizing amount of polyclonal neutralizing immunoglobulin (Ig purified from previously infected animals (SHIVIG or control Ig prior to intra-rectal challenge with SHIVSF162P4 and extensive longitudinal sampling was performed. SHIVIG treated animals exhibited significantly reduced viral load and increased de novo Env-specific plasma antibody. Dysregulation of the B cell profile was grossly apparent soon after infection in untreated animals; exemplified by a ≈50% decrease in total B cells in the blood evident 2-3 weeks post-infection which was not apparent in SHIVIG treated animals. IgD+CD5+CD21+ B cells phenotypically similar to marginal zone-like B cells were highly sensitive to SHIV infection, becoming significantly decreased as early as 3 days post-infection in control animals, while being maintained in SHIVIG treated animals, and were highly correlated with the induction of Env-specific plasma antibody. These results suggest that B cell dysregulation during the early stages of infection likely contributes to suboptimal Env-specific B cell and antibody responses, and strategies that limit this dysregulation may enhance the host's ability to eliminate HIV.

  11. Specifics of marketing strategy in the segment of high fashion

    OpenAIRE

    Butigan, Ružica; Grilec Kaurić, Alica; Ujević, Darko

    2013-01-01

    The success of high fashion designers is not only in a specificity of the products but also in specific and very well executed marketing strategy. Emphasis is placed on the design of very specific marketing program and marketing strategies that must concider all the characteristics of the high fashion market. Therefore, a scientific research problem is defined as follows: although the market of high fashion at first glance does not imply a completely different marketing approach than other fa...

  12. Segment-specific terminal sequences of Bunyamwera bunyavirus regulate genome replication

    International Nuclear Information System (INIS)

    Barr, John N.; Elliott, Richard M.; Dunn, Ewan F.; Wertz, Gail W.

    2003-01-01

    Bunyamwera virus (BUNV) is the prototype of both the Orthobunyavirus genus and the Bunyaviridae family of segmented negative sense RNA viruses. The tripartite BUNV genome consists of small (S), medium (M), and large (L) segments that are transcribed to give a single mRNA and replicated to generate an antigenome that is the template for synthesis of further genomic RNA strands. We modified an existing cDNA-derived RNA synthesis system to allow identification of BUNV RNA replication and transcription products by direct metabolic labeling. Direct RNA analysis allowed us to distinguish between template activities that affected either RNA replication or mRNA transcription, an ability that was not possible using previous reporter gene expression assays. We generated genome analogs containing the entire nontranslated terminal sequences of the S, M, and L BUNV segments surrounding a common sequence. Analysis of RNAs synthesized from these templates revealed that the relative abilities of BUNV segments to perform RNA replication was M > L > S. Exchange of segment-specific terminal nucleotides identified a 12-nt region located within both the 3' and 5' termini of the M segment that correlated with its high replication ability

  13. Spatially adapted augmentation of age-specific atlas-based segmentation using patch-based priors

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    Liu, Mengyuan; Seshamani, Sharmishtaa; Harrylock, Lisa; Kitsch, Averi; Miller, Steven; Chau, Van; Poskitt, Kenneth; Rousseau, Francois; Studholme, Colin

    2014-03-01

    One of the most common approaches to MRI brain tissue segmentation is to employ an atlas prior to initialize an Expectation- Maximization (EM) image labeling scheme using a statistical model of MRI intensities. This prior is commonly derived from a set of manually segmented training data from the population of interest. However, in cases where subject anatomy varies significantly from the prior anatomical average model (for example in the case where extreme developmental abnormalities or brain injuries occur), the prior tissue map does not provide adequate information about the observed MRI intensities to ensure the EM algorithm converges to an anatomically accurate labeling of the MRI. In this paper, we present a novel approach for automatic segmentation of such cases. This approach augments the atlas-based EM segmentation by exploring methods to build a hybrid tissue segmentation scheme that seeks to learn where an atlas prior fails (due to inadequate representation of anatomical variation in the statistical atlas) and utilize an alternative prior derived from a patch driven search of the atlas data. We describe a framework for incorporating this patch-based augmentation of EM (PBAEM) into a 4D age-specific atlas-based segmentation of developing brain anatomy. The proposed approach was evaluated on a set of MRI brain scans of premature neonates with ages ranging from 27.29 to 46.43 gestational weeks (GWs). Results indicated superior performance compared to the conventional atlas-based segmentation method, providing improved segmentation accuracy for gray matter, white matter, ventricles and sulcal CSF regions.

  14. Automated segmentation of tumors on bone scans using anatomy-specific thresholding

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    Chu, Gregory H.; Lo, Pechin; Kim, Hyun J.; Lu, Peiyun; Ramakrishna, Bharath; Gjertson, David; Poon, Cheryce; Auerbach, Martin; Goldin, Jonathan; Brown, Matthew S.

    2012-03-01

    Quantification of overall tumor area on bone scans may be a potential biomarker for treatment response assessment and has, to date, not been investigated. Segmentation of bone metastases on bone scans is a fundamental step for this response marker. In this paper, we propose a fully automated computerized method for the segmentation of bone metastases on bone scans, taking into account characteristics of different anatomic regions. A scan is first segmented into anatomic regions via an atlas-based segmentation procedure, which involves non-rigidly registering a labeled atlas scan to the patient scan. Next, an intensity normalization method is applied to account for varying levels of radiotracer dosing levels and scan timing. Lastly, lesions are segmented via anatomic regionspecific intensity thresholding. Thresholds are chosen by receiver operating characteristic (ROC) curve analysis against manual contouring by board certified nuclear medicine physicians. A leave-one-out cross validation of our method on a set of 39 bone scans with metastases marked by 2 board-certified nuclear medicine physicians yielded a median sensitivity of 95.5%, and specificity of 93.9%. Our method was compared with a global intensity thresholding method. The results show a comparable sensitivity and significantly improved overall specificity, with a p-value of 0.0069.

  15. Automatic prostate MR image segmentation with sparse label propagation and domain-specific manifold regularization.

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    Liao, Shu; Gao, Yaozong; Shi, Yinghuan; Yousuf, Ambereen; Karademir, Ibrahim; Oto, Aytekin; Shen, Dinggang

    2013-01-01

    Automatic prostate segmentation in MR images plays an important role in prostate cancer diagnosis. However, there are two main challenges: (1) Large inter-subject prostate shape variations; (2) Inhomogeneous prostate appearance. To address these challenges, we propose a new hierarchical prostate MR segmentation method, with the main contributions lying in the following aspects: First, the most salient features are learnt from atlases based on a subclass discriminant analysis (SDA) method, which aims to find a discriminant feature subspace by simultaneously maximizing the inter-class distance and minimizing the intra-class variations. The projected features, instead of only voxel-wise intensity, will be served as anatomical signature of each voxel. Second, based on the projected features, a new multi-atlases sparse label fusion framework is proposed to estimate the prostate likelihood of each voxel in the target image from the coarse level. Third, a domain-specific semi-supervised manifold regularization method is proposed to incorporate the most reliable patient-specific information identified by the prostate likelihood map to refine the segmentation result from the fine level. Our method is evaluated on a T2 weighted prostate MR image dataset consisting of 66 patients and compared with two state-of-the-art segmentation methods. Experimental results show that our method consistently achieves the highest segmentation accuracies than other methods under comparison.

  16. Development of inter-specific chromosomes segment substitution libraries (CSSL) in rice

    Science.gov (United States)

    Six libraries of inter-specific Chromosome Segment Substitution Lines (CSSLs) of rice are being developed as pre-breeding materials and genetic stocks. Three accessions of O. rufipogon were selected as donors, based on phylogenetic, geographical and morphological divergence, and crossed with two rec...

  17. On the importance of FIB-SEM specific segmentation algorithms for porous media

    Energy Technology Data Exchange (ETDEWEB)

    Salzer, Martin, E-mail: martin.salzer@uni-ulm.de [Institute of Stochastics, Faculty of Mathematics and Economics, Ulm University, D-89069 Ulm (Germany); Thiele, Simon, E-mail: simon.thiele@imtek.uni-freiburg.de [Laboratory for MEMS Applications, IMTEK, Department of Microsystems Engineering, University of Freiburg, D-79110 Freiburg (Germany); Zengerle, Roland, E-mail: zengerle@imtek.uni-freiburg.de [Laboratory for MEMS Applications, IMTEK, Department of Microsystems Engineering, University of Freiburg, D-79110 Freiburg (Germany); Schmidt, Volker, E-mail: volker.schmidt@uni-ulm.de [Institute of Stochastics, Faculty of Mathematics and Economics, Ulm University, D-89069 Ulm (Germany)

    2014-09-15

    A new algorithmic approach to segmentation of highly porous three dimensional image data gained by focused ion beam tomography is described which extends the key-principle of local threshold backpropagation described in Salzer et al. (2012). The technique of focused ion beam tomography has shown to be capable of imaging the microstructure of functional materials. In order to perform a quantitative analysis on the corresponding microstructure a segmentation task needs to be performed. However, algorithmic segmentation of images obtained with focused ion beam tomography is a challenging problem for highly porous materials if filling the pore phase, e.g. with epoxy resin, is difficult. The gray intensities of individual voxels are not sufficient to determine the phase represented by them and usual thresholding methods are not applicable. We thus propose a new approach to segmentation that pays respect to the specifics of the imaging process of focused ion beam tomography. As an application of our approach, the segmentation of three dimensional images for a cathode material used in polymer electrolyte membrane fuel cells is discussed. We show that our approach preserves significantly more of the original nanostructure than a thresholding approach. - Highlights: • We describe a new approach to the segmentation of FIB-SEM images of porous media. • The first and last occurrences of structures are detected by analysing the z-profiles. • The algorithm is validated by comparing it to a manual segmentation. • The new approach shows significantly less artifacts than a thresholding approach. • A structural analysis also shows improved results for the obtained microstructure.

  18. A data-driven modeling approach to identify disease-specific multi-organ networks driving physiological dysregulation.

    Directory of Open Access Journals (Sweden)

    Warren D Anderson

    2017-07-01

    Full Text Available Multiple physiological systems interact throughout the development of a complex disease. Knowledge of the dynamics and connectivity of interactions across physiological systems could facilitate the prevention or mitigation of organ damage underlying complex diseases, many of which are currently refractory to available therapeutics (e.g., hypertension. We studied the regulatory interactions operating within and across organs throughout disease development by integrating in vivo analysis of gene expression dynamics with a reverse engineering approach to infer data-driven dynamic network models of multi-organ gene regulatory influences. We obtained experimental data on the expression of 22 genes across five organs, over a time span that encompassed the development of autonomic nervous system dysfunction and hypertension. We pursued a unique approach for identification of continuous-time models that jointly described the dynamics and structure of multi-organ networks by estimating a sparse subset of ∼12,000 possible gene regulatory interactions. Our analyses revealed that an autonomic dysfunction-specific multi-organ sequence of gene expression activation patterns was associated with a distinct gene regulatory network. We analyzed the model structures for adaptation motifs, and identified disease-specific network motifs involving genes that exhibited aberrant temporal dynamics. Bioinformatic analyses identified disease-specific single nucleotide variants within or near transcription factor binding sites upstream of key genes implicated in maintaining physiological homeostasis. Our approach illustrates a novel framework for investigating the pathogenesis through model-based analysis of multi-organ system dynamics and network properties. Our results yielded novel candidate molecular targets driving the development of cardiovascular disease, metabolic syndrome, and immune dysfunction.

  19. A prosthesis-specific multi-link segment model of lower-limb amputee sprinting.

    Science.gov (United States)

    Rigney, Stacey M; Simmons, Anne; Kark, Lauren

    2016-10-03

    Lower-limb amputees commonly utilize non-articulating energy storage and return (ESAR) prostheses for high impact activities such as sprinting. Despite these prostheses lacking an articulating ankle joint, amputee gait analysis conventionally features a two-link segment model of the prosthetic foot. This paper investigated the effects of the selected link segment model׳s marker-set and geometry on a unilateral amputee sprinter׳s calculated lower-limb kinematics, kinetics and energetics. A total of five lower-limb models of the Ottobock ® 1E90 Sprinter were developed, including two conventional shank-foot models that each used a different version of the Plug-in-Gait (PiG) marker-set to test the effect of prosthesis ankle marker location. Two Hybrid prosthesis-specific models were then developed, also using the PiG marker-sets, with the anatomical shank and foot replaced by prosthesis-specific geometry separated into two segments. Finally, a Multi-link segment (MLS) model was developed, consisting of six segments for the prosthesis as defined by a custom marker-set. All full-body musculoskeletal models were tested using four trials of experimental marker trajectories within OpenSim 3.2 (Stanford, California, USA) to find the affected and unaffected hip, knee and ankle kinematics, kinetics and energetics. The geometry of the selected lower-limb prosthesis model was found to significantly affect all variables on the affected leg (p prosthesis-specific spatial, inertial and elastic properties from full-body models significantly affects the calculated amputee gait characteristics, and we therefore recommend the implementation of a MLS model. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Segmenting CT prostate images using population and patient-specific statistics for radiotherapy

    International Nuclear Information System (INIS)

    Feng, Qianjin; Foskey, Mark; Chen Wufan; Shen Dinggang

    2010-01-01

    Purpose: In the segmentation of sequential treatment-time CT prostate images acquired in image-guided radiotherapy, accurately capturing the intrapatient variation of the patient under therapy is more important than capturing interpatient variation. However, using the traditional deformable-model-based segmentation methods, it is difficult to capture intrapatient variation when the number of samples from the same patient is limited. This article presents a new deformable model, designed specifically for segmenting sequential CT images of the prostate, which leverages both population and patient-specific statistics to accurately capture the intrapatient variation of the patient under therapy. Methods: The novelty of the proposed method is twofold: First, a weighted combination of gradient and probability distribution function (PDF) features is used to build the appearance model to guide model deformation. The strengths of each feature type are emphasized by dynamically adjusting the weight between the profile-based gradient features and the local-region-based PDF features during the optimization process. An additional novel aspect of the gradient-based features is that, to alleviate the effect of feature inconsistency in the regions of gas and bone adjacent to the prostate, the optimal profile length at each landmark is calculated by statistically investigating the intensity profile in the training set. The resulting gradient-PDF combined feature produces more accurate and robust segmentations than general gradient features. Second, an online learning mechanism is used to build shape and appearance statistics for accurately capturing intrapatient variation. Results: The performance of the proposed method was evaluated on 306 images of the 24 patients. Compared to traditional gradient features, the proposed gradient-PDF combination features brought 5.2% increment in the success ratio of segmentation (from 94.1% to 99.3%). To evaluate the effectiveness of online

  1. Segmenting CT prostate images using population and patient-specific statistics for radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Feng, Qianjin; Foskey, Mark; Chen Wufan; Shen Dinggang [Biomedical Engineering College, South Medical University, Guangzhou (China) and Department of Radiology, University of North Carolina, Chapel Hill, North Carolina 27510 (United States); Department of Radiation Oncology, University of North Carolina, Chapel Hill, North Carolina 27599 (United States); Biomedical Engineering College, South Medical University, Guangzhou 510510 (China); Department of Radiology, University of North Carolina, Chapel Hill, North Carolina 27510 (United States)

    2010-08-15

    Purpose: In the segmentation of sequential treatment-time CT prostate images acquired in image-guided radiotherapy, accurately capturing the intrapatient variation of the patient under therapy is more important than capturing interpatient variation. However, using the traditional deformable-model-based segmentation methods, it is difficult to capture intrapatient variation when the number of samples from the same patient is limited. This article presents a new deformable model, designed specifically for segmenting sequential CT images of the prostate, which leverages both population and patient-specific statistics to accurately capture the intrapatient variation of the patient under therapy. Methods: The novelty of the proposed method is twofold: First, a weighted combination of gradient and probability distribution function (PDF) features is used to build the appearance model to guide model deformation. The strengths of each feature type are emphasized by dynamically adjusting the weight between the profile-based gradient features and the local-region-based PDF features during the optimization process. An additional novel aspect of the gradient-based features is that, to alleviate the effect of feature inconsistency in the regions of gas and bone adjacent to the prostate, the optimal profile length at each landmark is calculated by statistically investigating the intensity profile in the training set. The resulting gradient-PDF combined feature produces more accurate and robust segmentations than general gradient features. Second, an online learning mechanism is used to build shape and appearance statistics for accurately capturing intrapatient variation. Results: The performance of the proposed method was evaluated on 306 images of the 24 patients. Compared to traditional gradient features, the proposed gradient-PDF combination features brought 5.2% increment in the success ratio of segmentation (from 94.1% to 99.3%). To evaluate the effectiveness of online

  2. Subject-Specific Sparse Dictionary Learning for Atlas-Based Brain MRI Segmentation.

    Science.gov (United States)

    Roy, Snehashis; He, Qing; Sweeney, Elizabeth; Carass, Aaron; Reich, Daniel S; Prince, Jerry L; Pham, Dzung L

    2015-09-01

    Quantitative measurements from segmentations of human brain magnetic resonance (MR) images provide important biomarkers for normal aging and disease progression. In this paper, we propose a patch-based tissue classification method from MR images that uses a sparse dictionary learning approach and atlas priors. Training data for the method consists of an atlas MR image, prior information maps depicting where different tissues are expected to be located, and a hard segmentation. Unlike most atlas-based classification methods that require deformable registration of the atlas priors to the subject, only affine registration is required between the subject and training atlas. A subject-specific patch dictionary is created by learning relevant patches from the atlas. Then the subject patches are modeled as sparse combinations of learned atlas patches leading to tissue memberships at each voxel. The combination of prior information in an example-based framework enables us to distinguish tissues having similar intensities but different spatial locations. We demonstrate the efficacy of the approach on the application of whole-brain tissue segmentation in subjects with healthy anatomy and normal pressure hydrocephalus, as well as lesion segmentation in multiple sclerosis patients. For each application, quantitative comparisons are made against publicly available state-of-the art approaches.

  3. Scan-rescan reproducibility of segmental aortic wall shear stress as assessed by phase-specific segmentation with 4D flow MRI in healthy volunteers.

    Science.gov (United States)

    van der Palen, Roel L F; Roest, Arno A W; van den Boogaard, Pieter J; de Roos, Albert; Blom, Nico A; Westenberg, Jos J M

    2018-05-26

    The aim was to investigate scan-rescan reproducibility and observer variability of segmental aortic 3D systolic wall shear stress (WSS) by phase-specific segmentation with 4D flow MRI in healthy volunteers. Ten healthy volunteers (age 26.5 ± 2.6 years) underwent aortic 4D flow MRI twice. Maximum 3D systolic WSS (WSSmax) and mean 3D systolic WSS (WSSmean) for five thoracic aortic segments over five systolic cardiac phases by phase-specific segmentations were calculated. Scan-rescan analysis and observer reproducibility analysis were performed. Scan-rescan data showed overall good reproducibility for WSSmean (coefficient of variation, COV 10-15%) with moderate-to-strong intraclass correlation coefficient (ICC 0.63-0.89). The variability in WSSmax was high (COV 16-31%) with moderate-to-good ICC (0.55-0.79) for different aortic segments. Intra- and interobserver reproducibility was good-to-excellent for regional aortic WSSmax (ICC ≥ 0.78; COV ≤ 17%) and strong-to-excellent for WSSmean (ICC ≥ 0.86; COV ≤ 11%). In general, ascending aortic segments showed more WSSmax/WSSmean variability compared to aortic arch or descending aortic segments for scan-rescan, intraobserver and interobserver comparison. Scan-rescan reproducibility was good for WSSmean and moderate for WSSmax for all thoracic aortic segments over multiple systolic phases in healthy volunteers. Intra/interobserver reproducibility for segmental WSS assessment was good-to-excellent. Variability of WSSmax is higher and should be taken into account in case of individual follow-up or in comparative rest-stress studies to avoid misinterpretation.

  4. Pancreas segmentation from 3D abdominal CT images using patient-specific weighted subspatial probabilistic atlases

    Science.gov (United States)

    Karasawa, Kenichi; Oda, Masahiro; Hayashi, Yuichiro; Nimura, Yukitaka; Kitasaka, Takayuki; Misawa, Kazunari; Fujiwara, Michitaka; Rueckert, Daniel; Mori, Kensaku

    2015-03-01

    Abdominal organ segmentations from CT volumes are now widely used in the computer-aided diagnosis and surgery assistance systems. Among abdominal organs, the pancreas is especially difficult to segment because of its large individual differences of the shape and position. In this paper, we propose a new pancreas segmentation method from 3D abdominal CT volumes using patient-specific weighted-subspatial probabilistic atlases. First of all, we perform normalization of organ shapes in training volumes and an input volume. We extract the Volume Of Interest (VOI) of the pancreas from the training volumes and an input volume. We divide each training VOI and input VOI into some cubic regions. We use a nonrigid registration method to register these cubic regions of the training VOI to corresponding regions of the input VOI. Based on the registration results, we calculate similarities between each cubic region of the training VOI and corresponding region of the input VOI. We select cubic regions of training volumes having the top N similarities in each cubic region. We subspatially construct probabilistic atlases weighted by the similarities in each cubic region. After integrating these probabilistic atlases in cubic regions into one, we perform a rough-to-precise segmentation of the pancreas using the atlas. The results of the experiments showed that utilization of the training volumes having the top N similarities in each cubic region led good results of the pancreas segmentation. The Jaccard Index and the average surface distance of the result were 58.9% and 2.04mm on average, respectively.

  5. Sport-Specific Training Targeting the Proximal Segments and Throwing Velocity in Collegiate Throwing Athletes

    Science.gov (United States)

    Palmer, Thomas; Uhl, Timothy L.; Howell, Dana; Hewett, Timothy E.; Viele, Kert; Mattacola, Carl G.

    2015-01-01

    Context The ability to generate, absorb, and transmit forces through the proximal segments of the pelvis, spine, and trunk has been proposed to influence sport performance, yet traditional training techniques targeting the proximal segments have had limited success improving sport-specific performance. Objective To investigate the effects of a traditional endurance-training program and a sport-specific power-training program targeting the muscles that support the proximal segments and throwing velocity. Design Randomized controlled clinical trial. Setting University research laboratory and gymnasium. Patients or Other Participants A total of 46 (age = 20 ± 1.3 years, height = 175.7 ± 8.7 cm) healthy National Collegiate Athletic Association Division III female softball (n = 17) and male baseball (n = 29) players. Intervention(s) Blocked stratification for sex and position was used to randomly assign participants to 1 of 2 training groups for 7 weeks: a traditional endurance-training group (ET group; n = 21) or a power-stability–training group (PS group; n = 25). Mean Outcome Measure(s) The change score in peak throwing velocity (km/h) normalized for body weight (BW; kilograms) and change score in tests that challenge the muscles of the proximal segments normalized for BW (kilograms). We used 2-tailed independent-samples t tests to compare differences between the change scores. Results The peak throwing velocity (ET group = 0.01 ± 0.1 km/h/kg of BW, PS group = 0.08 ± 0.03 km/h/kg of BW; P < .001) and muscle power outputs for the chop (ET group = 0.22 ± 0.91 W/kg of BW, PS group = 1.3 ± 0.91 W/kg of BW; P < .001) and lift (ET group = 0.59 ± 0.67 W/kg of BW, PS group = 1.4 ± 0.87 W/kg of BW; P < .001) tests were higher at postintervention in the PT than in the ET group. Conclusions An improvement in throwing velocity occurred simultaneously with measures of muscular endurance and power after a sport-specific training regimen targeting the proximal segments

  6. Reconsidering Emotion Dysregulation.

    Science.gov (United States)

    D'Agostino, Alessandra; Covanti, Serena; Rossi Monti, Mario; Starcevic, Vladan

    2017-12-01

    This article aims to review the concept of emotion dysregulation, focusing on issues related to its definition, meanings and role in psychiatric disorders. Articles on emotion dysregulation published until May 2016 were identified through electronic database searches. Although there is no agreement about the definition of emotion dysregulation, the following five overlapping, not mutually exclusive dimensions of emotion dysregulation were identified: decreased emotional awareness, inadequate emotional reactivity, intense experience and expression of emotions, emotional rigidity and cognitive reappraisal difficulty. These dimensions characterise a number of psychiatric disorders in various proportions, with borderline personality disorder and eating disorders seemingly more affected than other conditions. The present review contributes to the literature by identifying the key components of emotion dysregulation and by showing how these permeate various forms of psychopathology. It also makes suggestions for improving research endeavours. Better understanding of the various dimensions of emotion dysregulation will have implications for clinical practice. Future research needs to address emotion dysregulation in all its multifaceted complexity so that it becomes clearer what the concept encompasses.

  7. Generic method for automatic bladder segmentation on cone beam CT using a patient-specific bladder shape model

    International Nuclear Information System (INIS)

    Schoot, A. J. A. J. van de; Schooneveldt, G.; Wognum, S.; Stalpers, L. J. A.; Rasch, C. R. N.; Bel, A.; Hoogeman, M. S.; Chai, X.

    2014-01-01

    Purpose: The aim of this study is to develop and validate a generic method for automatic bladder segmentation on cone beam computed tomography (CBCT), independent of gender and treatment position (prone or supine), using only pretreatment imaging data. Methods: Data of 20 patients, treated for tumors in the pelvic region with the entire bladder visible on CT and CBCT, were divided into four equally sized groups based on gender and treatment position. The full and empty bladder contour, that can be acquired with pretreatment CT imaging, were used to generate a patient-specific bladder shape model. This model was used to guide the segmentation process on CBCT. To obtain the bladder segmentation, the reference bladder contour was deformed iteratively by maximizing the cross-correlation between directional grey value gradients over the reference and CBCT bladder edge. To overcome incorrect segmentations caused by CBCT image artifacts, automatic adaptations were implemented. Moreover, locally incorrect segmentations could be adapted manually. After each adapted segmentation, the bladder shape model was expanded and new shape patterns were calculated for following segmentations. All available CBCTs were used to validate the segmentation algorithm. The bladder segmentations were validated by comparison with the manual delineations and the segmentation performance was quantified using the Dice similarity coefficient (DSC), surface distance error (SDE) and SD of contour-to-contour distances. Also, bladder volumes obtained by manual delineations and segmentations were compared using a Bland-Altman error analysis. Results: The mean DSC, mean SDE, and mean SD of contour-to-contour distances between segmentations and manual delineations were 0.87, 0.27 cm and 0.22 cm (female, prone), 0.85, 0.28 cm and 0.22 cm (female, supine), 0.89, 0.21 cm and 0.17 cm (male, supine) and 0.88, 0.23 cm and 0.17 cm (male, prone), respectively. Manual local adaptations improved the segmentation

  8. Segment-specific responses of intestinal epithelium transcriptome to in-feed antibiotics in pigs.

    Science.gov (United States)

    Yu, Kaifan; Mu, Chunlong; Yang, Yuxiang; Su, Yong; Zhu, Weiyun

    2017-10-01

    Despite widespread use of antibiotics for treatment of human diseases and promotion of growth of agricultural animals, our understanding of their effects on the host is still very limited. We used a model in which pigs were fed with or without a cocktail of antibiotics and found, based on the denaturing gradient gel electrophoresis (DGGE) patterns, that the fecal bacteria from the treatment and control animals were distinct. Furthermore, the total bacterial population in the feces tended to be decreased by the antibiotic treatment ( P = 0.07), and the counts of Lactobacillus and Clostridium XIVa were significantly reduced ( P epithelium, we assessed gene expression profiles of the jejunum and ileum and their response to antibiotic administration. The results indicate that in-feed antibiotics increased expression of genes involved in immune functions in both the jejunum and ileum, some of which were clustered in the coexpression network. Gene ontology terms of metabolic processes were altered predominantly in the jejunum but not in the ileum. Notably, antibiotics diminished intestinal segment-specific transcriptional changes, especially for genes associated with metabolic functions. This study reveals segment-specific responses of host intestinal epithelium to in-feed antibiotics, which can be a valuable resource for deciphering antibiotic-microbiota-host interactions. Copyright © 2017 the American Physiological Society.

  9. Automated segmentation and reconstruction of patient-specific cardiac anatomy and pathology from in vivo MRI

    International Nuclear Information System (INIS)

    Ringenberg, Jordan; Deo, Makarand; Devabhaktuni, Vijay; Filgueiras-Rama, David; Pizarro, Gonzalo; Ibañez, Borja; Berenfeld, Omer; Boyers, Pamela; Gold, Jeffrey

    2012-01-01

    This paper presents an automated method to segment left ventricle (LV) tissues from functional and delayed-enhancement (DE) cardiac magnetic resonance imaging (MRI) scans using a sequential multi-step approach. First, a region of interest (ROI) is computed to create a subvolume around the LV using morphological operations and image arithmetic. From the subvolume, the myocardial contours are automatically delineated using difference of Gaussians (DoG) filters and GSV snakes. These contours are used as a mask to identify pathological tissues, such as fibrosis or scar, within the DE-MRI. The presented automated technique is able to accurately delineate the myocardium and identify the pathological tissue in patient sets. The results were validated by two expert cardiologists, and in one set the automated results are quantitatively and qualitatively compared with expert manual delineation. Furthermore, the method is patient-specific, performed on an entire patient MRI series. Thus, in addition to providing a quick analysis of individual MRI scans, the fully automated segmentation method is used for effectively tagging regions in order to reconstruct computerized patient-specific 3D cardiac models. These models can then be used in electrophysiological studies and surgical strategy planning. (paper)

  10. Host-Specific and Segment-Specific Evolutionary Dynamics of Avian and Human Influenza A Viruses: A Systematic Review

    KAUST Repository

    Kim, Kiyeon

    2016-01-13

    Understanding the evolutionary dynamics of influenza viruses is essential to control both avian and human influenza. Here, we analyze host-specific and segment-specific Tajima’s D trends of influenza A virus through a systematic review using viral sequences registered in the National Center for Biotechnology Information. To avoid bias from viral population subdivision, viral sequences were stratified according to their sampling locations and sampling years. As a result, we obtained a total of 580 datasets each of which consists of nucleotide sequences of influenza A viruses isolated from a single population of hosts at a single sampling site within a single year. By analyzing nucleotide sequences in the datasets, we found that Tajima’s D values of viral sequences were different depending on hosts and gene segments. Tajima’s D values of viruses isolated from chicken and human samples showed negative, suggesting purifying selection or a rapid population growth of the viruses. The negative Tajima’s D values in rapidly growing viral population were also observed in computer simulations. Tajima’s D values of PB2, PB1, PA, NP, and M genes of the viruses circulating in wild mallards were close to zero, suggesting that these genes have undergone neutral selection in constant-sized population. On the other hand, Tajima’s D values of HA and NA genes of these viruses were positive, indicating HA and NA have undergone balancing selection in wild mallards. Taken together, these results indicated the existence of unknown factors that maintain viral subtypes in wild mallards.

  11. Host-Specific and Segment-Specific Evolutionary Dynamics of Avian and Human Influenza A Viruses: A Systematic Review

    KAUST Repository

    Kim, Kiyeon; Omori, Ryosuke; Ueno, Keisuke; Iida, Sayaka; Ito, Kimihito

    2016-01-01

    Understanding the evolutionary dynamics of influenza viruses is essential to control both avian and human influenza. Here, we analyze host-specific and segment-specific Tajima’s D trends of influenza A virus through a systematic review using viral sequences registered in the National Center for Biotechnology Information. To avoid bias from viral population subdivision, viral sequences were stratified according to their sampling locations and sampling years. As a result, we obtained a total of 580 datasets each of which consists of nucleotide sequences of influenza A viruses isolated from a single population of hosts at a single sampling site within a single year. By analyzing nucleotide sequences in the datasets, we found that Tajima’s D values of viral sequences were different depending on hosts and gene segments. Tajima’s D values of viruses isolated from chicken and human samples showed negative, suggesting purifying selection or a rapid population growth of the viruses. The negative Tajima’s D values in rapidly growing viral population were also observed in computer simulations. Tajima’s D values of PB2, PB1, PA, NP, and M genes of the viruses circulating in wild mallards were close to zero, suggesting that these genes have undergone neutral selection in constant-sized population. On the other hand, Tajima’s D values of HA and NA genes of these viruses were positive, indicating HA and NA have undergone balancing selection in wild mallards. Taken together, these results indicated the existence of unknown factors that maintain viral subtypes in wild mallards.

  12. Disruptive Mood Dysregulation Disorder

    Science.gov (United States)

    ... Application Process Managing Grants Clinical Research Training Small Business Research Labs at NIMH Labs at NIMH Home Research ... Chat on Disruptive Mood Dysregulation Disorder (Archived Transcript) Research and ... Journal Articles: References and abstracts from MEDLINE/PubMed (National ...

  13. Automatized spleen segmentation in non-contrast-enhanced MR volume data using subject-specific shape priors

    Science.gov (United States)

    Gloger, Oliver; Tönnies, Klaus; Bülow, Robin; Völzke, Henry

    2017-07-01

    To develop the first fully automated 3D spleen segmentation framework derived from T1-weighted magnetic resonance (MR) imaging data and to verify its performance for spleen delineation and volumetry. This approach considers the issue of low contrast between spleen and adjacent tissue in non-contrast-enhanced MR images. Native T1-weighted MR volume data was performed on a 1.5 T MR system in an epidemiological study. We analyzed random subsamples of MR examinations without pathologies to develop and verify the spleen segmentation framework. The framework is modularized to include different kinds of prior knowledge into the segmentation pipeline. Classification by support vector machines differentiates between five different shape types in computed foreground probability maps and recognizes characteristic spleen regions in axial slices of MR volume data. A spleen-shape space generated by training produces subject-specific prior shape knowledge that is then incorporated into a final 3D level set segmentation method. Individually adapted shape-driven forces as well as image-driven forces resulting from refined foreground probability maps steer the level set successfully to the segment the spleen. The framework achieves promising segmentation results with mean Dice coefficients of nearly 0.91 and low volumetric mean errors of 6.3%. The presented spleen segmentation approach can delineate spleen tissue in native MR volume data. Several kinds of prior shape knowledge including subject-specific 3D prior shape knowledge can be used to guide segmentation processes achieving promising results.

  14. Bayesian longitudinal segmentation of hippocampal substructures in brain MRI using subject-specific atlases.

    Science.gov (United States)

    Iglesias, Juan Eugenio; Van Leemput, Koen; Augustinack, Jean; Insausti, Ricardo; Fischl, Bruce; Reuter, Martin

    2016-11-01

    The hippocampal formation is a complex, heterogeneous structure that consists of a number of distinct, interacting subregions. Atrophy of these subregions is implied in a variety of neurodegenerative diseases, most prominently in Alzheimer's disease (AD). Thanks to the increasing resolution of MR images and computational atlases, automatic segmentation of hippocampal subregions is becoming feasible in MRI scans. Here we introduce a generative model for dedicated longitudinal segmentation that relies on subject-specific atlases. The segmentations of the scans at the different time points are jointly computed using Bayesian inference. All time points are treated the same to avoid processing bias. We evaluate this approach using over 4700 scans from two publicly available datasets (ADNI and MIRIAD). In test-retest reliability experiments, the proposed method yielded significantly lower volume differences and significantly higher Dice overlaps than the cross-sectional approach for nearly every subregion (average across subregions: 4.5% vs. 6.5%, Dice overlap: 81.8% vs. 75.4%). The longitudinal algorithm also demonstrated increased sensitivity to group differences: in MIRIAD (69 subjects: 46 with AD and 23 controls), it found differences in atrophy rates between AD and controls that the cross sectional method could not detect in a number of subregions: right parasubiculum, left and right presubiculum, right subiculum, left dentate gyrus, left CA4, left HATA and right tail. In ADNI (836 subjects: 369 with AD, 215 with early cognitive impairment - eMCI - and 252 controls), all methods found significant differences between AD and controls, but the proposed longitudinal algorithm detected differences between controls and eMCI and differences between eMCI and AD that the cross sectional method could not find: left presubiculum, right subiculum, left and right parasubiculum, left and right HATA. Moreover, many of the differences that the cross-sectional method already found

  15. Sphingosine-1-Phosphate Evokes Unique Segment-Specific Vasoconstriction of the Renal Microvasculature

    Science.gov (United States)

    Singletary, Sean T.; Cook, Anthony K.; Hobbs, Janet L.; Pollock, Jennifer S.; Inscho, Edward W.

    2014-01-01

    Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, has been implicated in regulating vascular tone and participating in chronic and acute kidney injury. However, little is known about the role of S1P in the renal microcirculation. Here, we directly assessed the vasoresponsiveness of preglomerular and postglomerular microvascular segments to exogenous S1P using the in vitro blood-perfused juxtamedullary nephron preparation. Superfusion of S1P (0.001–10 μM) evoked concentration-dependent vasoconstriction in preglomerular microvessels, predominantly afferent arterioles. After administration of 10 μM S1P, the diameter of afferent arterioles decreased to 35%±5% of the control diameter, whereas the diameters of interlobular and arcuate arteries declined to 50%±12% and 68%±6% of the control diameter, respectively. Notably, efferent arterioles did not respond to S1P. The S1P receptor agonists FTY720 and FTY720-phosphate and the specific S1P1 receptor agonist SEW2871 each evoked modest afferent arteriolar vasoconstriction. Conversely, S1P2 receptor inhibition with JTE-013 significantly attenuated S1P-mediated afferent arteriolar vasoconstriction. Moreover, blockade of L-type voltage-dependent calcium channels with diltiazem or nifedipine attenuated S1P-mediated vasoconstriction. Intravenous injection of S1P in anesthetized rats reduced renal blood flow dose dependently. Western blotting and immunofluorescence revealed S1P1 and S1P2 receptor expression in isolated preglomerular microvessels and microvascular smooth muscle cells. These data demonstrate that S1P evokes segmentally distinct preglomerular vasoconstriction via activation of S1P1 and/or S1P2 receptors, partially via L-type voltage-dependent calcium channels. Accordingly, S1P may have a novel function in regulating afferent arteriolar resistance under physiologic conditions. PMID:24578134

  16. Automatic segmentation of thoracic and pelvic CT images for radiotherapy planning using implicit anatomic knowledge and organ-specific segmentation strategies

    International Nuclear Information System (INIS)

    Haas, B; Coradi, T; Scholz, M; Kunz, P; Huber, M; Oppitz, U; Andre, L; Lengkeek, V; Huyskens, D; Esch, A van; Reddick, R

    2008-01-01

    structures on the scale 1-excellent (no corrections necessary, maximum time saving), 2-good (corrections necessary for up to 1/3 of slices), 3-acceptable (major corrections necessary, but still time saving), 4-not acceptable (manual redrawing more efficient, no time saving). A rating ≤ 3 indicates a time saving in the treatment planning process and was given for pelvis segmentation in 70% (I) and 68% (II) of the cases, with average ratings 2.9 (I) and 2.6 (II). For the thorax, a rating ≤ 3 was given in 94% and 91% of the cases, with average ratings 2.1 and 1.9, respectively. For quantitative validation, automatically generated structures were compared geometrically in 2D and 3D to manually drawn structures created by experts on seven randomly selected cases. The quantitative validation was limited to pelvis structures. The results indicate that the accuracy of the algorithms is within the bandwidth of manual segmentation by experts, except for specific erroneous situations. Even though manual review and corrections of automatically segmented structures are still mandatory, it can be expected that due to the speed of the presented software and the quality of its results, its introduction in the radiotherapy treatment planning process will lead to a considerable amount of time being saved

  17. EFFECTS OF PARENT ARTERY SEGMENTATION AND ANEURISMALWALL ELASTICITY ON PATIENT-SPECIFIC HEMODYNAMIC SIMULATIONS

    Institute of Scientific and Technical Information of China (English)

    CHEN Jia-liang; DING Guang-hong; YANG Xin-jian; LI Hai-yun

    2011-01-01

    It is well known that hemodynamics and wall tension play an important role in the formation,growth and rupture of aneurysms.In the present study,the authors investigated the influence of parent artery segmentation and aneurismal-wall elasticity on patient-specific hemodynamic simulations with two patient-specific eases of cerebral aneurysms.Realistic models of the aneurysms were constructed from 3-D angiography images and blood flow dynamics was studied under physiologically representative waveform of inflow.For each aneurysm three computational models were constructed:Model 1 with more extensive upstream parent artery with the rigid arterial and aneurismal wall,Model 2 with the partial upstream parent artery with the elastic arterial and aneurismal wall,Model 3 with more extensive upstream parent artery with the rigid wall for arterial wall far from the aneurysm and the elastic wall for arterial wall near the aneurysm.The results show that Model 1 could predict complex intra-aneurismal flow patterns and wall shear stress distribution in the aneurysm,but is unable to give aneurismal wall deformation and tension,Model 2 demonstrates aneurismal wall deformation and tension,but fails to properly model inflow pattern contributed by the upstream parent artery,resulting in local misunderstanding Wall Shear Stress (WSS) distribution,Model 3 can overcome limitations of the former two models,and give an overall and accurate analysis on intra-aneurismal flow patterns,wall shear stress distribution,aneurismal-wall deformation and tension.Therefore we suggest that the proper length of extensive upstream parent artery and aneuri-smal-wall elasticity should be considered carefully in establishing computational model to predict the intra-aneurismal hemodynamic and wall tension.

  18. Automatic bladder segmentation on CBCT for multiple plan ART of bladder cancer using a patient-specific bladder model

    Energy Technology Data Exchange (ETDEWEB)

    Xiangfei, Chai; Hulshof, Maarten; Bel, Arjan [Department of Radiotherapy, Academic medical Center, University of Amsterdam, 1105 AZ, Amsterdam (Netherlands); Van Herk, Marcel; Betgen, Anja [Department of Radiotherapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, 1066 CX, Amsterdam (Netherlands)

    2012-06-21

    In multiple plan adaptive radiotherapy (ART) strategies of bladder cancer, a library of plans corresponding to different bladder volumes is created based on images acquired in early treatment sessions. Subsequently, the plan for the smallest PTV safely covering the bladder on cone-beam CT (CBCT) is selected as the plan of the day. The aim of this study is to develop an automatic bladder segmentation approach suitable for CBCT scans and test its ability to select the appropriate plan from the library of plans for such an ART procedure. Twenty-three bladder cancer patients with a planning CT and on average 11.6 CBCT scans were included in our study. For each patient, all CBCT scans were matched to the planning CT on bony anatomy. Bladder contours were manually delineated for each planning CT (for model building) and CBCT (for model building and validation). The automatic segmentation method consisted of two steps. A patient-specific bladder deformation model was built from the training data set of each patient (the planning CT and the first five CBCT scans). Then, the model was applied to automatically segment bladders in the validation data of the same patient (the remaining CBCT scans). Principal component analysis (PCA) was applied to the training data to model patient-specific bladder deformation patterns. The number of PCA modes for each patient was chosen such that the bladder shapes in the training set could be represented by such number of PCA modes with less than 0.1 cm mean residual error. The automatic segmentation started from the bladder shape of a reference CBCT, which was adjusted by changing the weight of each PCA mode. As a result, the segmentation contour was deformed consistently with the training set to fit the bladder in the validation image. A cost function was defined by the absolute difference between the directional gradient field of reference CBCT sampled on the corresponding bladder contour and the directional gradient field of validation

  19. Automatic bladder segmentation on CBCT for multiple plan ART of bladder cancer using a patient-specific bladder model

    International Nuclear Information System (INIS)

    Chai Xiangfei; Hulshof, Maarten; Bel, Arjan; Van Herk, Marcel; Betgen, Anja

    2012-01-01

    In multiple plan adaptive radiotherapy (ART) strategies of bladder cancer, a library of plans corresponding to different bladder volumes is created based on images acquired in early treatment sessions. Subsequently, the plan for the smallest PTV safely covering the bladder on cone-beam CT (CBCT) is selected as the plan of the day. The aim of this study is to develop an automatic bladder segmentation approach suitable for CBCT scans and test its ability to select the appropriate plan from the library of plans for such an ART procedure. Twenty-three bladder cancer patients with a planning CT and on average 11.6 CBCT scans were included in our study. For each patient, all CBCT scans were matched to the planning CT on bony anatomy. Bladder contours were manually delineated for each planning CT (for model building) and CBCT (for model building and validation). The automatic segmentation method consisted of two steps. A patient-specific bladder deformation model was built from the training data set of each patient (the planning CT and the first five CBCT scans). Then, the model was applied to automatically segment bladders in the validation data of the same patient (the remaining CBCT scans). Principal component analysis (PCA) was applied to the training data to model patient-specific bladder deformation patterns. The number of PCA modes for each patient was chosen such that the bladder shapes in the training set could be represented by such number of PCA modes with less than 0.1 cm mean residual error. The automatic segmentation started from the bladder shape of a reference CBCT, which was adjusted by changing the weight of each PCA mode. As a result, the segmentation contour was deformed consistently with the training set to fit the bladder in the validation image. A cost function was defined by the absolute difference between the directional gradient field of reference CBCT sampled on the corresponding bladder contour and the directional gradient field of validation

  20. Dynamic Parameter Identification of Subject-Specific Body Segment Parameters Using Robotics Formalism: Case Study Head Complex.

    Science.gov (United States)

    Díaz-Rodríguez, Miguel; Valera, Angel; Page, Alvaro; Besa, Antonio; Mata, Vicente

    2016-05-01

    Accurate knowledge of body segment inertia parameters (BSIP) improves the assessment of dynamic analysis based on biomechanical models, which is of paramount importance in fields such as sport activities or impact crash test. Early approaches for BSIP identification rely on the experiments conducted on cadavers or through imaging techniques conducted on living subjects. Recent approaches for BSIP identification rely on inverse dynamic modeling. However, most of the approaches are focused on the entire body, and verification of BSIP for dynamic analysis for distal segment or chain of segments, which has proven to be of significant importance in impact test studies, is rarely established. Previous studies have suggested that BSIP should be obtained by using subject-specific identification techniques. To this end, our paper develops a novel approach for estimating subject-specific BSIP based on static and dynamics identification models (SIM, DIM). We test the validity of SIM and DIM by comparing the results using parameters obtained from a regression model proposed by De Leva (1996, "Adjustments to Zatsiorsky-Seluyanov's Segment Inertia Parameters," J. Biomech., 29(9), pp. 1223-1230). Both SIM and DIM are developed considering robotics formalism. First, the static model allows the mass and center of gravity (COG) to be estimated. Second, the results from the static model are included in the dynamics equation allowing us to estimate the moment of inertia (MOI). As a case study, we applied the approach to evaluate the dynamics modeling of the head complex. Findings provide some insight into the validity not only of the proposed method but also of the application proposed by De Leva (1996, "Adjustments to Zatsiorsky-Seluyanov's Segment Inertia Parameters," J. Biomech., 29(9), pp. 1223-1230) for dynamic modeling of body segments.

  1. Nephron segment specific microRNA biomarkers of pre-clinical drug-induced renal toxicity: Opportunities and challenges

    Energy Technology Data Exchange (ETDEWEB)

    Nassirpour, Rounak, E-mail: Rounak.nassirpour@pfizer.com [Drug Safety, Pfizer Worldwide Research and Development, 1 Burtt Rd, Andover, MA 01810 (United States); Ramaiah, Shashi K. [Drug Safety, Pfizer Worldwide Research and Development, 610 Main Street, Cambridge, MA 02139 (United States); Whiteley, Laurence O. [Drug Safety, Pfizer Worldwide Research and Development, 1 Burtt Rd, Andover, MA 01810 (United States)

    2016-12-01

    Drug-induced nephrotoxicity is a common drug development complication for pharmaceutical companies. Sensitive, specific, translatable and non-invasive biomarkers of renal toxicity are urgently needed to diagnose nephron segment specific injury. The currently available gold standard biomarkers for nephrotoxicity are not kidney-specific, lack sensitivity for early detection, and are not suitable for renal damage localization (glomerular vs tubulointerstitial injury). MicroRNAs (miRNAs) are increasingly gaining momentum as promising biomarkers of various organ toxicities, including drug induced renal injury. This is mostly due to their stability in easily accessible biofluids, ease of developing nucleic acids detection compared to protein detection assays, as well as their interspecies translatability. Increasing concordance of miRNA findings by standardizing methodology most suitable for their detection and quantitation, as well as characterization of their expression pattern in a cell type specific manner, will accelerate progress toward validation of these miRNAs as biomarkers in pre-clinical, and clinical settings. This review aims to highlight the current pre-clinical findings surrounding miRNAs as biomarkers in two important segments of the nephron, the glomerulus and tubules. - Highlights: • miRNAs are promising biomarkers of drug-induced kidney injury. • Summarized pre-clinical miRNA biomarkers of drug-induced nephrotoxicity. • Described the strengths and challenges associated with miRNAs as biomarkers.

  2. Phosphatidylcholine Specific PLC-Induced Dysregulation of Gap Junctions, a Robust Cellular Response to Environmental Toxicants, and Prevention by Resveratrol in a Rat Liver Cell Model

    Czech Academy of Sciences Publication Activity Database

    Sovadinová, I.; Babica, Pavel; Böke, H.; Kumar, E.; Wilke, A.; Park, J.-S.; Trosko, J. E.; Upham, B. L.

    2015-01-01

    Roč. 10, 5 no.e0124454 (2015), s. 1-16 E-ISSN 1932-6203 R&D Projects: GA MŠk LH12034 Institutional support: RVO:67985939 Keywords : gap junctional intercellular communication * resveratrol * phosphatidylcholine-specific phospholipase C Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.057, year: 2015

  3. A systematic review of image segmentation methodology, used in the additive manufacture of patient-specific 3D printed models of the cardiovascular system

    Directory of Open Access Journals (Sweden)

    N Byrne

    2016-04-01

    Full Text Available Background Shortcomings in existing methods of image segmentation preclude the widespread adoption of patient-specific 3D printing as a routine decision-making tool in the care of those with congenital heart disease. We sought to determine the range of cardiovascular segmentation methods and how long each of these methods takes. Methods A systematic review of literature was undertaken. Medical imaging modality, segmentation methods, segmentation time, segmentation descriptive quality (SDQ and segmentation software were recorded. Results Totally 136 studies met the inclusion criteria (1 clinical trial; 80 journal articles; 55 conference, technical and case reports. The most frequently used image segmentation methods were brightness thresholding, region growing and manual editing, as supported by the most popular piece of proprietary software: Mimics (Materialise NV, Leuven, Belgium, 1992–2015. The use of bespoke software developed by individual authors was not uncommon. SDQ indicated that reporting of image segmentation methods was generally poor with only one in three accounts providing sufficient detail for their procedure to be reproduced. Conclusions and implication of key findings Predominantly anecdotal and case reporting precluded rigorous assessment of risk of bias and strength of evidence. This review finds a reliance on manual and semi-automated segmentation methods which demand a high level of expertise and a significant time commitment on the part of the operator. In light of the findings, we have made recommendations regarding reporting of 3D printing studies. We anticipate that these findings will encourage the development of advanced image segmentation methods.

  4. Toward Patient Specific Long Lasting Metallic Implants for Mandibular Segmental Defects

    Science.gov (United States)

    Shayesteh Moghaddam, Narges

    Mandibular defects may result from tumor resection, trauma, or inflammation. The goals of mandibular reconstruction surgeries are to restore mandible function and aesthetics. To this end, surgeons use a combination of bone grafts and metallic implants. These implants have drastically different mechanical properties than the surrounding bone. As a result, the stress distribution in the mandible changes after surgery. The long-term abnormal stress/strain distribution may lead to either graft failure due to bone resorption as a result of stress shielding, or hardware failure due to stress concentrations. During the healing period of six to nine months it is important that complete immobilization, bringing mandibular micro-motion down to the level of 200-500 mum during chewing, is achieved. After this period it is desired that bone undergo normal stress for long-term success of the treatment. Although current high stiffness fixation hardware accomplishes this immobilization during the healing period, the hardware continues to alter the normal stress-strain trajectory seen during chewing once the engrafted bone heals. Over the long-term, the immobilized and stress-shielded engrafted bone tends to resorb. On the other hand, hardware fracturing or/and screw loosening is observed as the stress is concentrated at certain locations on the hardware. Equally as important is the permanent loss of chewing power due to the altered stress-strain relationships. The first stage of this research is to study the problems encountered following a mandibular segmental defect reconstructive surgery. To this end, we constructed a finite element model of a healthy mandible, which includes cortical and cancellous bone, teeth (enamel and dentin components), and the periodontal ligament. Using this model, we studied a healthy adult mandible under maximum molar bite force for stress, strain, displacement, and reaction force distribution. For mandibular segmental defect reconstruction the

  5. Multi-criteria media mix decision model for advertising multiple product with segment specific and mass media

    Directory of Open Access Journals (Sweden)

    Sugandha Aggarwal

    2014-12-01

    Full Text Available Judicious media planning decisions are crucial for successful advertising of products. Media planners extensively use mathematical models supplemented with market research and expert opinion to devise the media plans. Media planning models discussed in the literature largely focus on single products with limited studies related to the multi-product media planning. In this paper we propose a media planning model to allocate limited advertising budget among multiple products advertised in a segmented market and determine the number of advertisements to be given in different media. The proposed model is formulated considering both segment specific and mass media vehicles to maximize the total advertising reach for each product. The model also incorporates the cross product effect of advertising of one product on the other. The proposed formulation is a multi-objective linear integer programming model and interactive linear integer goal programming is discussed to solve the model. A real life case study is presented to illustrate the application of the proposed model.

  6. Active Segmentation.

    Science.gov (United States)

    Mishra, Ajay; Aloimonos, Yiannis

    2009-01-01

    The human visual system observes and understands a scene/image by making a series of fixations. Every fixation point lies inside a particular region of arbitrary shape and size in the scene which can either be an object or just a part of it. We define as a basic segmentation problem the task of segmenting that region containing the fixation point. Segmenting the region containing the fixation is equivalent to finding the enclosing contour- a connected set of boundary edge fragments in the edge map of the scene - around the fixation. This enclosing contour should be a depth boundary.We present here a novel algorithm that finds this bounding contour and achieves the segmentation of one object, given the fixation. The proposed segmentation framework combines monocular cues (color/intensity/texture) with stereo and/or motion, in a cue independent manner. The semantic robots of the immediate future will be able to use this algorithm to automatically find objects in any environment. The capability of automatically segmenting objects in their visual field can bring the visual processing to the next level. Our approach is different from current approaches. While existing work attempts to segment the whole scene at once into many areas, we segment only one image region, specifically the one containing the fixation point. Experiments with real imagery collected by our active robot and from the known databases 1 demonstrate the promise of the approach.

  7. Epigenetic Dysregulation in Laryngeal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Thian-Sze Wong

    2012-01-01

    Full Text Available Laryngeal carcinoma is a common head and neck cancer with poor prognosis. Patients with laryngeal carcinoma usually present late leading to the reduced treatment efficacy and high rate of recurrence. Despite the advance in the use of molecular markers for monitoring human cancers in the past decades, there are still no reliable markers for use to screen laryngeal carcinoma and follow the patients after treatment. Epigenetics emerged as an important field in understanding the biology of the human malignancies. Epigenetic alterations refer to the dysregulation of gene, which do not involve the alterations of the DNA sequence. Major epigenetic changes including methylation imbalance, histone modification, and small RNA dysregulation could play a role in the development of human malignancies. Global epigenetic change is now regarded as a molecular signature of cancer. The characteristics and behavior of a cancer could be predicted based on the specific epigenetic pattern. We here provide a review on the understanding of epigenetic dysregulation in laryngeal carcinoma. Further knowledge on the initiation and progression of laryngeal carcinoma at epigenetic level could promote the translation of the knowledge to clinical use.

  8. Segmentation: Identification of consumer segments

    DEFF Research Database (Denmark)

    Høg, Esben

    2005-01-01

    It is very common to categorise people, especially in the advertising business. Also traditional marketing theory has taken in consumer segments as a favorite topic. Segmentation is closely related to the broader concept of classification. From a historical point of view, classification has its...... origin in other sciences as for example biology, anthropology etc. From an economic point of view, it is called segmentation when specific scientific techniques are used to classify consumers to different characteristic groupings. What is the purpose of segmentation? For example, to be able to obtain...... a basic understanding of grouping people. Advertising agencies may use segmentation totarget advertisements, while food companies may usesegmentation to develop products to various groups of consumers. MAPP has for example investigated the positioning of fish in relation to other food products...

  9. Colorimetric Detection of Specific DNA Segments Amplified by Polymerase Chain Reactions

    Science.gov (United States)

    Kemp, David J.; Smith, Donald B.; Foote, Simon J.; Samaras, N.; Peterson, M. Gregory

    1989-04-01

    The polymerase chain reaction (PCR) procedure has many potential applications in mass screening. We describe here a general assay for colorimetric detection of amplified DNA. The target DNA is first amplified by PCR, and then a second set of oligonucleotides, nested between the first two, is incorporated by three or more PCR cycles. These oligonucleotides bear ligands: for example, one can be biotinylated and the other can contain a site for a double-stranded DNA-binding protein. After linkage to an immobilized affinity reagent (such as a cloned DNA-binding protein, which we describe here) and labeling with a second affinity reagent (for example, avidin) linked to horseradish peroxidase, reaction with a chromogenic substrate allows detection of the amplified DNA. This amplified DNA assay (ADA) is rapid, is readily applicable to mass screening, and uses routine equipment. We show here that it can be used to detect human immunodeficiency virus sequences specifically against a background of human DNA.

  10. Segmentation of electric energy customers by specific niches; Segmentacao de clientes de energia eletrica por nichos especiais

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Ana Lucia Rodrigues da; Jannuzzi, Gilberto de Martino [Universidade Estadual de Campinas (UNICAMP), SP (Brazil)], E-mail: jannuzzi@fen.unicamp.br

    2009-04-15

    The article presents the classic segmentation used in electric energy industry for large customers. The paper argues the limitations of this classification, as well as, the potentialities to classify customers for specific niches, the example of that already occurs in other competitive sectors of the economy. Twelve potential forms for classifying large customers in electricity industry are presented: geographic localization; value of the invoice; sector of productive activity; types of share holding composition and enterprise management; forms and characteristics of the use of the electric energy in the final units; degree of technological sophistication; client relation cost benefit; common factors in energy process of purchase; brand associated with the customer; extraordinary factors, such as, urgency, application and volume of energy; personal characteristics of the purchaser in charge of the operation; former-customers who moved from the captive market to the free market and vice versa. The article concludes proposing a new methodology to identify the specific niches of customers in the electric sector, as well as the inductive and restrictive factors of this methodology. (author)

  11. A distance measurement between specific sites on the cytoplasmic surface of bovine rhodopsin in rod outer segment disk membranes.

    Science.gov (United States)

    Albert, A D; Watts, A; Spooner, P; Groebner, G; Young, J; Yeagle, P L

    1997-08-14

    Structural information on mammalian integral membrane proteins is scarce. As part of work on an alternative approach to the structure of bovine rhodopsin, a method was devised to obtain an intramolecular distance between two specific sites on rhodopsin while in the rod outer segment disk membrane. In this report, the distance between the rhodopsin kinase phosphorylation site(s) on the carboxyl terminal and the top of the third transmembrane helix was measured on native rhodopsin. Rhodopsin was labeled with a nuclear spin label (31P) by limited phosphorylation with rhodopsin kinase. Major phosphorylation occurs at serines 343 and 338 on the carboxyl terminal. The phosphorylated rhodopsin was then specifically labeled on cysteine 140 with an electron spin label. Magic angle spinning 31P-nuclear magnetic resonance revealed the resonance arising from the phosphorylated protein. The enhancement of the transverse relaxation of this resonance by the paramagnetic spin label was observed. The strength of this perturbation was used to determine the through-space distance between the phosphorylation site(s) and the spin label position. A distance of 18 +/- 3 A was obtained.

  12. Computed tomography landmark-based semi-automated mesh morphing and mapping techniques: generation of patient specific models of the human pelvis without segmentation.

    Science.gov (United States)

    Salo, Zoryana; Beek, Maarten; Wright, David; Whyne, Cari Marisa

    2015-04-13

    Current methods for the development of pelvic finite element (FE) models generally are based upon specimen specific computed tomography (CT) data. This approach has traditionally required segmentation of CT data sets, which is time consuming and necessitates high levels of user intervention due to the complex pelvic anatomy. The purpose of this research was to develop and assess CT landmark-based semi-automated mesh morphing and mapping techniques to aid the generation and mechanical analysis of specimen-specific FE models of the pelvis without the need for segmentation. A specimen-specific pelvic FE model (source) was created using traditional segmentation methods and morphed onto a CT scan of a different (target) pelvis using a landmark-based method. The morphed model was then refined through mesh mapping by moving the nodes to the bone boundary. A second target model was created using traditional segmentation techniques. CT intensity based material properties were assigned to the morphed/mapped model and to the traditionally segmented target models. Models were analyzed to evaluate their geometric concurrency and strain patterns. Strains generated in a double-leg stance configuration were compared to experimental strain gauge data generated from the same target cadaver pelvis. CT landmark-based morphing and mapping techniques were efficiently applied to create a geometrically multifaceted specimen-specific pelvic FE model, which was similar to the traditionally segmented target model and better replicated the experimental strain results (R(2)=0.873). This study has shown that mesh morphing and mapping represents an efficient validated approach for pelvic FE model generation without the need for segmentation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Disordered eating and emotion dysregulation among adolescents and their parents.

    Science.gov (United States)

    Hansson, Erika; Daukantaité, Daiva; Johnsson, Per

    2017-04-04

    Research on the relationships between adolescent and parental disordered eating (DE) and emotion dysregulation is scarce. Thus, the aim of this study was to explore whether mothers' and fathers' own DE, as measured by SCOFF questionnaire, and emotion dysregulation, as measured by the difficulties in emotion regulation scale (DERS), were associated with their daughters' or sons' DE and emotion dysregulation. Furthermore, the importance of shared family meals and possible parent-related predictors of adolescent DE were explored. The total sample comprised 1,265 adolescents (M age  = 16.19, SD = 1.21; age range 13.5-19 years, 54.5% female) whose parents had received a self-report questionnaire via mail. Of these, 235 adolescents (18.6% of the total sample) whose parents completed the questionnaire were used in the analyses. Parents' responses were matched and compared with those of their child. Adolescent girls showed greater levels of DE overall than did their parents. Furthermore, DE was associated with emotion dysregulation among both adolescents and parents. Adolescent and parental emotion dysregulation was associated, although there were gender differences in the specifics of this relationship. The frequency of shared dinner meals was the only variable that was associated to DE and emotion dysregulation among adolescents, while parental eating disorder was the only variable that enhanced the probability of adolescent DE. The present study contributes to the literature by demonstrating that there are significant associations between parents and their adolescent children in terms of DE, emotion dysregulation, and shared family meals. Future studies should break down these relationships among mothers, fathers, girls, and boys to further clarify the specific associational, and possibly predictive, directions.

  14. A Positive Affective Neuroendocrinology (PANE Approach to Reward and Behavioral Dysregulation

    Directory of Open Access Journals (Sweden)

    Keith eWelker

    2015-07-01

    Full Text Available Emerging lines of research suggest that both testosterone and maladaptive reward processing can modulate behavioral dysregulation. Yet to date, no integrative account has been provided that systematically explains neuroendocrine function, dysregulation of reward, and behavioral dysregulation in a unified perspective. This is particularly important given specific neuroendocrine systems are potential mechanisms underlying and giving rise to reward-relevant behaviors. In this review, we propose a forward thinking approach to study the mechanisms of reward and behavioral dysregulation from a positive affective neuroendocrinology (PANE perspective. This approach holds that testosterone increases reward processing, which increases the likelihood of behavioral dysregulation. Additionally, the PANE framework holds that reward processing mediates the effects of testosterone on behavioral dysregulation. We also explore sources of potential sex differences and the roles of age, cortisol, and individual differences within the PANE framework. Finally, we discuss future prospects for research questions and methodology in the emerging field of affective neuroendocrinology.

  15. Specific expression of the vacuolar iron transporter, TgVit, causes iron accumulation in blue-colored inner bottom segments of various tulip petals.

    Science.gov (United States)

    Momonoi, Kazumi; Tsuji, Toshiaki; Kazuma, Kohei; Yoshida, Kumi

    2012-01-01

    Several flowers of Tulipa gesneriana exhibit a blue color in the bottom segments of the inner perianth. We have previously reported the inner-bottom tissue-specific iron accumulation and expression of the vacuolar iron transporter, TgVit1, in tulip cv. Murasakizuisho. To clarify whether the TgVit1-dependent iron accumulation and blue-color development in tulip petals are universal, we analyzed anthocyanin, its co-pigment components, iron contents and the expression of TgVit1 mRNA in 13 cultivars which show a blue color in the bottom segments of the inner perianth accompanying yellow- and white-colored inner-bottom petals. All of the blue bottom segments contained the same anthocyanin component, delphinidin 3-rutinoside. The flavonol composition varied with cultivar and tissue part. The major flavonol in the bottom segments of the inner perianth was rutin. The iron content in the upper part was less than that in the bottom segments of the inner perianth. The iron content in the yellow and white petals was higher in the bottom segment of the inner perianth than in the upper tissues. TgVit1 mRNA expression was apparent in all of the bottom tissues of the inner perianth. The result of a reproduction experiment by mixing the constituents suggests that the blue coloration in tulip petals is generally caused by iron complexation to delphinidin 3-rutinoside and that the iron complex is solubilized and stabilized by flavonol glycosides. TgVit1-dependent iron accumulation in the bottom segments of the inner perianth might be controlled by an unknown system that differentiated the upper parts and bottom segments of the inner perianth.

  16. Genetic variation of the Borrelia burgdorferi gene vlsE involves cassette-specific, segmental gene conversion.

    Science.gov (United States)

    Zhang, J R; Norris, S J

    1998-08-01

    The Lyme disease spirochete Borrelia burgdorferi possesses 15 silent vls cassettes and a vls expression site (vlsE) encoding a surface-exposed lipoprotein. Segments of the silent vls cassettes have been shown to recombine with the vlsE cassette region in the mammalian host, resulting in combinatorial antigenic variation. Despite promiscuous recombination within the vlsE cassette region, the 5' and 3' coding sequences of vlsE that flank the cassette region are not subject to sequence variation during these recombination events. The segments of the silent vls cassettes recombine in the vlsE cassette region through a unidirectional process such that the sequence and organization of the silent vls loci are not affected. As a result of recombination, the previously expressed segments are replaced by incoming segments and apparently degraded. These results provide evidence for a gene conversion mechanism in VlsE antigenic variation.

  17. Site-specific deletions of chromosomally located DNA segments with the multimer resolution system of broad-host-range plasmid RP4

    DEFF Research Database (Denmark)

    Sternberg, Claus; Eberl, Leo; Sanchezromero, Juan M.

    1995-01-01

    The multimer resolution system (mrs) of the broad-host-range plasmid RP4 has been exploited to develop a general method that permits the precise excision of chromosomal segments in a variety of gram-negative bacteria. The procedure is based on the site-specific recombination between two directly ...

  18. The Child Behavior Checklist Dysregulation Profile in Preschool Children: A Broad Dysregulation Syndrome.

    Science.gov (United States)

    Geeraerts, Sanne Barbara; Deutz, Marike Hester Francisca; Deković, Maja; Bunte, Tessa; Schoemaker, Kim; Espy, Kimberly Andrews; Prinzie, Peter; van Baar, Anneloes; Matthys, Walter

    2015-07-01

    Children with concurrent impairments in regulating affect, behavior, and cognition can be identified with the Anxious/Depressed, Aggressive Behavior, and Attention Problems scales (or AAA scales) of the Child Behavior Checklist (CBCL). Jointly, these scales form the Dysregulation Profile (DP). Despite persuasive evidence that DP is a marker for severe developmental problems, no consensus exists on the preferred conceptualization and operationalization of DP in preschool years. We addressed this concern by testing and validating the factor structure of DP in a group of predominantly clinically referred preschool children. Participants were 247 children (195 boys and 52 girls), aged 3.5 to 5.5 years. Children were assessed at baseline and 18 months later, using parent and teacher reports, a clinical interview with parents, behavioral observations, and neuropsychological tasks. Confirmatory factor analysis showed that a bifactor model, with a general DP factor and 3 specific factors representing the AAA scales, fitted the data better than a second-order model and a one-factor model for both parent-reported and teacher-reported child problem behavior. Criterion validity analyses showed that the DP factor was concurrently and longitudinally associated with markers of dysregulation and clinically relevant criteria, whereas the specific factors representing the AAA scales were more differentially related to those criteria. DP is best conceptualized as a broad syndrome of dysregulation that exists in addition to the specific syndromes as represented by the AAA scales. Implications for researchers and clinicians are discussed. Copyright © 2015 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Micro-segmental hair analysis for proving drug-facilitated crimes: Evidence that a victim ingested a sleeping aid, diphenhydramine, on a specific day.

    Science.gov (United States)

    Kuwayama, Kenji; Nariai, Maika; Miyaguchi, Hajime; Iwata, Yuko T; Kanamori, Tatsuyuki; Tsujikawa, Kenji; Yamamuro, Tadashi; Segawa, Hiroki; Abe, Hiroko; Iwase, Hirotaro; Inoue, Hiroyuki

    2018-07-01

    Sleeping aids are often abused in the commission of drug-facilitated crimes. Generally, there is little evidence that a victim ingested a spiked drink unknowingly because the unconscious victim cannot report the situation to the police immediately after the crime occurred. Although conventional segmental hair analysis can estimate the number of months since a targeted drug was ingested, this analysis cannot determine the specific day of ingestion. We recently developed a method of micro-segmental hair analysis using internal temporal markers (ITMs) to estimate the day of drug ingestion. This method was based on volunteer ingestion of ITMs to determine a timescale within individual hair strands, by segmenting a single hair strand at 0.4-mm intervals, corresponding to daily hair growth. This study assessed the ability of this method to estimate the day of ingestion of an over-the-counter sleeping aid, diphenhydramine, which can be easily abused. To model ingestion of a diphenhydramine-spiked drink unknowingly, each subject ingested a dose of diphenhydramine, followed by ingestion of two doses of the ITM, chlorpheniramine, 14days apart. Several hair strands were collected from each subject's scalp several weeks after the second ITM ingestion. Diphenhydramine and ITM were detected at specific regions within individual hair strands. The day of diphenhydramine ingestion was estimated from the distances between the regions and the days of ITM ingestion. The error between estimated and actual ingestion day ranged from -0.1 to 1.9days regardless of subjects and hair collection times. The total time required for micro-segmental analysis of 96 hair segments (hair length: 3.84cm) was approximately 2days and the cost was almost the same as in general drug analysis. This procedure may be applicable to the investigation of crimes facilitated by various drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Expression of Aleutian mink disease parvovirus capsid proteins in defined segments: localization of immunoreactive sites and neutralizing epitopes to specific regions.

    Science.gov (United States)

    Bloom, M E; Martin, D A; Oie, K L; Huhtanen, M E; Costello, F; Wolfinbarger, J B; Hayes, S F; Agbandje-McKenna, M

    1997-01-01

    The capsid proteins of the ADV-G isolate of Aleutian mink disease parvovirus (ADV) were expressed in 10 nonoverlapping segments as fusions with maltose-binding protein in pMAL-C2 (pVP1, pVP2a through pVP2i). The constructs were designed to capture the VP1 unique sequence and the portions analogous to the four variable surface loops of canine parvovirus (CPV) in individual fragments (pVP2b, pVP2d, pVP2e, and pVP2g, respectively). The panel of fusion proteins was immunoblotted with sera from mink infected with ADV. Seropositive mink infected with either ADV-TR, ADV-Utah, or ADV-Pullman reacted preferentially against certain segments, regardless of mink genotype or virus inoculum. The most consistently immunoreactive regions were pVP2g, pVP2e, and pVP2f, the segments that encompassed the analogs of CPV surface loops 3 and 4. The VP1 unique region was also consistently immunoreactive. These findings indicated that infected mink recognize linear epitopes that localized to certain regions of the capsid protein sequence. The segment containing the hypervariable region (pVP2d), corresponding to CPV loop 2, was also expressed from ADV-Utah. An anti-ADV-G monoclonal antibody and a rabbit anti-ADV-G capsid antibody reacted exclusively with the ADV-G pVP2d segment but not with the corresponding segment from ADV-Utah. Mink infected with ADV-TR or ADV-Utah also preferentially reacted with the pVP2d sequence characteristic of that virus. These results suggested that the loop 2 region may contain a type-specific linear epitope and that the epitope may also be specifically recognized by infected mink. Heterologous antisera were prepared against the VP1 unique region and the four segments capturing the variable surface loops of CPV. The antisera against the proteins containing loop 3 or loop 4, as well as the anticapsid antibody, neutralized ADV-G infectivity in vitro and bound to capsids in immune electron microscopy. These results suggested that regions of the ADV capsid proteins

  1. DEGAS: de novo discovery of dysregulated pathways in human diseases.

    Directory of Open Access Journals (Sweden)

    Igor Ulitsky

    Full Text Available BACKGROUND: Molecular studies of the human disease transcriptome typically involve a search for genes whose expression is significantly dysregulated in sick individuals compared to healthy controls. Recent studies have found that only a small number of the genes in human disease-related pathways show consistent dysregulation in sick individuals. However, those studies found that some pathway genes are affected in most sick individuals, but genes can differ among individuals. While a pathway is usually defined as a set of genes known to share a specific function, pathway boundaries are frequently difficult to assign, and methods that rely on such definition cannot discover novel pathways. Protein interaction networks can potentially be used to overcome these problems. METHODOLOGY/PRINCIPAL FINDINGS: We present DEGAS (DysrEgulated Gene set Analysis via Subnetworks, a method for identifying connected gene subnetworks significantly enriched for genes that are dysregulated in specimens of a disease. We applied DEGAS to seven human diseases and obtained statistically significant results that appear to home in on compact pathways enriched with hallmarks of the diseases. In Parkinson's disease, we provide novel evidence for involvement of mRNA splicing, cell proliferation, and the 14-3-3 complex in the disease progression. DEGAS is available as part of the MATISSE software package (http://acgt.cs.tau.ac.il/matisse. CONCLUSIONS/SIGNIFICANCE: The subnetworks identified by DEGAS can provide a signature of the disease potentially useful for diagnosis, pinpoint possible pathways affected by the disease, and suggest targets for drug intervention.

  2. Dysregulated pH in Tumor Microenvironment Checkmates Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Jaleh Barar

    2013-12-01

    Full Text Available Introduction: The dysregulation of pH by cancerous cells of solid tumors is able to create a unique milieu that is in favor of progression, invasion and metastasis as well as chemo-/immuno-resistance traits of solid tumors. Bioelements involved in pH dysregulation provide new set of oncotargets, inhibition of which may result in better clinical outcome. Methods: To study the impacts of pH dysregulation, we investigated the tumor development and progression in relation with Warburg effect, glycolysis and formation of aberrant tumor microenvironment. Results: The upregulation of glucose transporter GLUT-1 and several enzymes involve in glycolysis exacerbates this phenomenon. The accumulation of lactic acids in cancer cells provokes upregulation of several transport machineries (MCT-1, NHE-1, CA IX and H+ pump V-ATPase resulting in reinforced efflux of proton into extracellular fluid. This deviant event makes pH to be settled at 7.4 and 6.6 respectively in cancer cells cytoplasm and extracellular fluid within the tumor microenvironment, which in return triggers secretion of lysosomal components (various enzymes in acidic milieu with pH 5 into cytoplasm. All these anomalous phenomena make tumor microenvironment (TME to be exposed to cocktail of various enzymes with acidic pH, upon which extracellular matrix (ECM can be remodeled and even deformed, resulting in emergence of a complex viscose TME with high interstitial fluid pressure. Conclusion: It seems that pH dysregulation is able to remodel various physiologic functions and make solid tumors to become much more invasive and metastatic. It also can cause undesired resistance to chemotherapy and immunotherapy. Hence, cancer therapy needs to be reinforced using specific inhibitors of bioelements involved in pH dysregulation of TME in solid tumors.

  3. What are Segments in Google Analytics

    Science.gov (United States)

    Segments find all sessions that meet a specific condition. You can then apply this segment to any report in Google Analytics (GA). Segments are a way of identifying sessions and users while filters identify specific events, like pageviews.

  4. Dysregulated metabolism contributes to oncogenesis

    Science.gov (United States)

    Hirschey, Matthew D.; DeBerardinis, Ralph J.; Diehl, Anna Mae E.; Drew, Janice E.; Frezza, Christian; Green, Michelle F.; Jones, Lee W.; Ko, Young H.; Le, Anne; Lea, Michael A.; Locasale, Jason W.; Longo, Valter D.; Lyssiotis, Costas A.; McDonnell, Eoin; Mehrmohamadi, Mahya; Michelotti, Gregory; Muralidhar, Vinayak; Murphy, Michael P.; Pedersen, Peter L.; Poore, Brad; Raffaghello, Lizzia; Rathmell, Jeffrey C.; Sivanand, Sharanya; Vander Heiden, Matthew G.; Wellen, Kathryn E.

    2015-01-01

    Cancer is a disease characterized by unrestrained cellular proliferation. In order to sustain growth, cancer cells undergo a complex metabolic rearrangement characterized by changes in metabolic pathways involved in energy production and biosynthetic processes. The relevance of the metabolic transformation of cancer cells has been recently included in the updated version of the review “Hallmarks of Cancer”, where the dysregulation of cellular metabolism was included as an emerging hallmark. While several lines of evidence suggest that metabolic rewiring is orchestrated by the concerted action of oncogenes and tumor suppressor genes, in some circumstances altered metabolism can play a primary role in oncogenesis. Recently, mutations of cytosolic and mitochondrial enzymes involved in key metabolic pathways have been associated with hereditary and sporadic forms of cancer. Together, these results suggest that aberrant metabolism, once seen just as an epiphenomenon of oncogenic reprogramming, plays a key role in oncogenesis with the power to control both genetic and epigenetic events in cells. In this review, we discuss the relationship between metabolism and cancer, as part of a larger effort to identify a broad-spectrum of therapeutic approaches. We focus on major alterations in nutrient metabolism and the emerging link between metabolism and epigenetics. Finally, we discuss potential strategies to manipulate metabolism in cancer and tradeoffs that should be considered. More research on the suite of metabolic alterations in cancer holds the potential to discover novel approaches to treat it. PMID:26454069

  5. SAAS-CNV: A Joint Segmentation Approach on Aggregated and Allele Specific Signals for the Identification of Somatic Copy Number Alterations with Next-Generation Sequencing Data.

    Science.gov (United States)

    Zhang, Zhongyang; Hao, Ke

    2015-11-01

    Cancer genomes exhibit profound somatic copy number alterations (SCNAs). Studying tumor SCNAs using massively parallel sequencing provides unprecedented resolution and meanwhile gives rise to new challenges in data analysis, complicated by tumor aneuploidy and heterogeneity as well as normal cell contamination. While the majority of read depth based methods utilize total sequencing depth alone for SCNA inference, the allele specific signals are undervalued. We proposed a joint segmentation and inference approach using both signals to meet some of the challenges. Our method consists of four major steps: 1) extracting read depth supporting reference and alternative alleles at each SNP/Indel locus and comparing the total read depth and alternative allele proportion between tumor and matched normal sample; 2) performing joint segmentation on the two signal dimensions; 3) correcting the copy number baseline from which the SCNA state is determined; 4) calling SCNA state for each segment based on both signal dimensions. The method is applicable to whole exome/genome sequencing (WES/WGS) as well as SNP array data in a tumor-control study. We applied the method to a dataset containing no SCNAs to test the specificity, created by pairing sequencing replicates of a single HapMap sample as normal/tumor pairs, as well as a large-scale WGS dataset consisting of 88 liver tumors along with adjacent normal tissues. Compared with representative methods, our method demonstrated improved accuracy, scalability to large cancer studies, capability in handling both sequencing and SNP array data, and the potential to improve the estimation of tumor ploidy and purity.

  6. Axodendritic sorting and pathological missorting of Tau are isoform-specific and determined by axon initial segment architecture.

    Science.gov (United States)

    Zempel, Hans; Dennissen, Frank J A; Kumar, Yatender; Luedtke, Julia; Biernat, Jacek; Mandelkow, Eva-Maria; Mandelkow, Eckhard

    2017-07-21

    Subcellular mislocalization of the microtubule-associated protein Tau is a hallmark of Alzheimer disease (AD) and other tauopathies. Six Tau isoforms, differentiated by the presence or absence of a second repeat or of N-terminal inserts, exist in the human CNS, but their physiological and pathological differences have long remained elusive. Here, we investigated the properties and distributions of human and rodent Tau isoforms in primary forebrain rodent neurons. We found that the Tau diffusion barrier (TDB), located within the axon initial segment (AIS), controls retrograde (axon-to-soma) and anterograde (soma-to-axon) traffic of Tau. Tau isoforms without the N-terminal inserts were sorted efficiently into the axon. However, the longest isoform (2N4R-Tau) was partially retained in cell bodies and dendrites, where it accelerated spine and dendrite growth. The TDB (located within the AIS) was impaired when AIS components (ankyrin G, EB1) were knocked down or when glycogen synthase kinase-3β (GSK3β; an AD-associated kinase tethered to the AIS) was overexpressed. Using superresolution nanoscopy and live-cell imaging, we observed that microtubules within the AIS appeared highly dynamic, a feature essential for the TDB. Pathomechanistically, amyloid-β insult caused cofilin activation and F-actin remodeling and decreased microtubule dynamics in the AIS. Concomitantly with these amyloid-β-induced disruptions, the AIS/TDB sorting function failed, causing AD-like Tau missorting. In summary, we provide evidence that the human and rodent Tau isoforms differ in axodendritic sorting and amyloid-β-induced missorting and that the axodendritic distribution of Tau depends on AIS integrity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. MicroRNA function and dysregulation in bone tumors: the evidence to date

    International Nuclear Information System (INIS)

    Nugent, Mary

    2014-01-01

    Micro ribonucleic acids (miRNAs) are small non-coding RNA segments that have a role in the regulation of normal cellular development and proliferation including normal osteogenesis. They exert their effects through inhibition of specific target genes at the post-transcriptional level. Many miRNAs have altered expression levels in cancer (either increased or decreased depending on the specific miRNA). Altered miRNA expression profiles have been identified in several malignancies including primary bone tumors such as osteosarcoma and Ewing’s sarcoma. It is thought that they may function as tumor suppressor genes or oncogenes and hence when dysregulated contribute to the initiation and progression of malignancy. miRNAs are also thought to have a role in the development of bone metastases in other malignancies. In addition, evidence increasingly suggests that miRNAs may play a part in determining the response to chemotherapy in the treatment of osteosarcoma. These molecules are readily detectable in tissues, both fresh and formalin fixed paraffin embedded and, more recently, in blood. Although there are fewer published studies regarding circulating miRNA profiles, they appear to reflect changes in tissue expression. Thus miRNAs may serve as potential indicators of disease presence but more importantly, may have a role in disease characterization or as potential therapeutic targets. This review gives a brief overview of miRNA biochemistry and explores the evidence to date implicating these small molecules in the pathogenesis of bone tumors

  8. MicroRNA function and dysregulation in bone tumors: the evidence to date.

    LENUS (Irish Health Repository)

    Nugent, Mary

    2014-01-01

    Micro ribonucleic acids (miRNAs) are small non-coding RNA segments that have a role in the regulation of normal cellular development and proliferation including normal osteogenesis. They exert their effects through inhibition of specific target genes at the post-transcriptional level. Many miRNAs have altered expression levels in cancer (either increased or decreased depending on the specific miRNA). Altered miRNA expression profiles have been identified in several malignancies including primary bone tumors such as osteosarcoma and Ewing\\'s sarcoma. It is thought that they may function as tumor suppressor genes or oncogenes and hence when dysregulated contribute to the initiation and progression of malignancy. miRNAs are also thought to have a role in the development of bone metastases in other malignancies. In addition, evidence increasingly suggests that miRNAs may play a part in determining the response to chemotherapy in the treatment of osteosarcoma. These molecules are readily detectable in tissues, both fresh and formalin fixed paraffin embedded and, more recently, in blood. Although there are fewer published studies regarding circulating miRNA profiles, they appear to reflect changes in tissue expression. Thus miRNAs may serve as potential indicators of disease presence but more importantly, may have a role in disease characterization or as potential therapeutic targets. This review gives a brief overview of miRNA biochemistry and explores the evidence to date implicating these small molecules in the pathogenesis of bone tumors.

  9. Dynamic multi-segmental postural control in patients with chronic non-specific low back pain compared to pain-free controls: A cross-sectional study.

    Science.gov (United States)

    McCaskey, Michael A; Wirth, Brigitte; Schuster-Amft, Corina; de Bruin, Eling D

    2018-01-01

    Reduced postural control is thought to contribute to the development and persistence of chronic non-specific low back pain (CNLBP). It is therefore frequently assessed in affected patients and commonly reported as the average amount of postural sway while standing upright under a variety of sensory conditions. These averaged linear outcomes, such as mean centre of pressure (CP) displacement or mean CP surface areas, may not reflect the true postural status. Adding nonlinear outcomes and multi-segmental kinematic analysis has been reported to better reflect the complexity of postural control and may detect subtler postural differences. In this cross-sectional study, a combination of linear and nonlinear postural parameters were assessed in patients with CNLBP (n = 24, 24-75 years, 9 females) and compared to symptom-free controls (CG, n = 34, 22-67 years, 11 females). Primary outcome was postural control measured by variance of joint configurations (uncontrolled manifold index, UI), confidence ellipse surface areas (CEA) and approximate entropy (ApEn) of CP dispersion during the response phase of a perturbed postural control task on a swaying platform. Secondary outcomes were segment excursions and clinical outcome correlates for pain and function. Non-parametric tests for group comparison with P-adjustment for multiple comparisons were conducted. Principal component analysis was applied to identify patterns of segmental contribution in both groups. CNLBP and CG performed similarly with respect to the primary outcomes. Comparison of joint kinematics revealed significant differences of hip (P postural differences in CNLBP patients with low to moderate pain status.

  10. Timing of birth: Parsimony favors strategic over dysregulated parturition.

    Science.gov (United States)

    Catalano, Ralph; Goodman, Julia; Margerison-Zilko, Claire; Falconi, April; Gemmill, Alison; Karasek, Deborah; Anderson, Elizabeth

    2016-01-01

    The "dysregulated parturition" narrative posits that the human stress response includes a cascade of hormones that "dysregulates" and accelerates parturition but provides questionable utility as a guide to understand or prevent preterm birth. We offer and test a "strategic parturition" narrative that not only predicts the excess preterm births that dysregulated parturition predicts but also makes testable, sex-specific predictions of the effect of stressful environments on the timing of birth among term pregnancies. We use interrupted time-series modeling of cohorts conceived over 101 months to test for lengthening of early term male gestations in stressed population. We use an event widely reported to have stressed Americans and to have increased the incidence of low birth weight and fetal death across the country-the terrorist attacks of September 2001. We tested the hypothesis that the odds of male infants conceived in December 2000 (i.e., at term in September 2001) being born early as opposed to full term fell below the value expected from those conceived in the 50 prior and 50 following months. We found that term male gestations exposed to the terrorist attacks exhibited 4% lower likelihood of early, as opposed to full or late, term birth. Strategic parturition explains observed data for which the dysregulated parturition narrative offers no prediction-the timing of birth among gestations stressed at term. Our narrative may help explain why findings from studies examining associations between population- and/or individual-level stressors and preterm birth are generally mixed. © 2015 Wiley Periodicals, Inc.

  11. Side chain requirements for affinity and specificity in D5, an HIV-1 antibody derived from the VH1-69 germline segment.

    Science.gov (United States)

    Stewart, Alex; Harrison, Joseph S; Regula, Lauren K; Lai, Jonathan R

    2013-04-08

    Analysis of factors contributing to high affinity antibody-protein interactions provides insight into natural antibody evolution, and guides the design of antibodies with new or enhanced function. We previously studied the interaction between antibody D5 and its target, a designed protein based on HIV-1 gp41 known as 5-Helix, as a model system [Da Silva, G. F.; Harrison, J. S.; Lai, J. R., Biochemistry, 2010, 49, 5464-5472]. Antibody D5 represents an interesting case study because it is derived from the VH1-69 germline segment; this germline segment is characterized by a hydrophobic second heavy chain complementarity determining region (HCDR2) that constitutes the major functional paratope in D5 and several antibodies derived from the same progenitor. Here we explore side chain requirements for affinity and specificity in D5 using phage display. Two D5-based libraries were prepared that contained diversity in all three light chain complementarity determining regions (LCDRs 1-3), and in the third HCDR (HCDR3). The first library allowed residues to vary among a restricted set of six amino acids (Tyr/Ala/Asp/Ser/His/Pro; D5-Lib-I). The second library was designed based on a survey of existing VH1-69 antibody structures (D5-Lib-II). Both libraries were subjected to multiple rounds of selection against 5-Helix, and individual clones characterized. We found that selectants from D5-Lib-I generally had moderate affinity and specificity, while many clones from D5-Lib-II exhibited D5-like properties. Additional analysis of the D5-Lib-II functional population revealed position-specific biases for particular amino acids, many that differed from the identity of those side chains in D5. Together these results suggest that there is some permissiveness for alternative side chains in the LCDRs and HCDR3 of D5, but that replacement with a minimal set of residues is not tolerated in this scaffold for 5-Helix recognition. This work provides novel information about this high

  12. Specification of a Human Reliability Data Bank for conducting HRA segments of PRAs for nuclear power plants

    International Nuclear Information System (INIS)

    Comer, M.K.; Donovan, M.D.

    1985-02-01

    The US Nuclear Regulatory Commission (NRC), Sandia National Laboratories (SNL), and General Physics Corporation have conducted a research program to develop a Human Reliability Data Bank for nuclear power industry probabilistic risk assessment (PRA). As part of this program, a survey of existing human reliability data banks from other industries was conducted and a concept of a Data Bank for the nuclear industry was developed. The results of these efforts were published in the two volumes of NUREG/CR-2744: ''Human Reliability Data Bank for Nuclear Power Plant Operations: Volume 1, A Review of Existing Human Reliability Data Banks, and Volume 2, A Data Bank Concept and System Description.'' This document, NUREG/CR-4010, is the revised technical specification for the Human Reliability Data Bank. The organization of the Data Bank and a description of a data publication, the Human Reliability Data Manual, are provided. Details of the administration and operation of the Data Bank are discussed. Appendices present the detailed procedures for processing data, revising the Data Manual, operating the Data Bank, and reviewing data for the Data Bank. The final appendix is a skeleton version (structure only) of the Data Manual

  13. Investigating multiple dysregulated pathways in rheumatoid arthritis ...

    Indian Academy of Sciences (India)

    Xian-Dong Song

    2018-03-09

    Mar 9, 2018 ... 5Department of Kidney Internal Medicine, Hongqi Hospital of ... on the gene expression profile, pathway data, and PPI information. ... controls. These 10 dysregulated pathways might be potential ... a significant burden on the healthcare systems (Yamada ... The risk of adverse effects and expensive treat-.

  14. Disruptive mood dysregulation disorder: current insights

    Directory of Open Access Journals (Sweden)

    Baweja R

    2016-08-01

    Full Text Available Raman Baweja, Susan D Mayes, Usman Hameed, James G Waxmonsky Department of Psychiatry, Penn State University College of Medicine, Hershey, PA, USA Abstract: Disruptive mood dysregulation disorder (DMDD was introduced as a new diagnostic entity under the category of depressive disorders in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5. It was included in DSM-5 primarily to address concerns about the misdiagnosis and consequent overtreatment of bipolar disorder in children and adolescents. DMDD does provide a home for a large percentage of referred children with severe persistent irritability that did not fit well into any DSM, Fourth Edition (DSM-IV diagnostic category. However, it has been a controversial addition to the DSM-5 due to lack of published validity studies, leading to questions about its validity as a distinct disorder. In this article, the authors discuss the diagnostic criteria, assessment, epidemiology, criticism of the diagnosis, and pathophysiology, as well as treatment and future directions for DMDD. They also review the literature on severe mood dysregulation, as described by the National Institute of Mental Health, as the scientific support for DMDD is based primarily on studies of severe mood dysregulation. Keywords: disruptive mood dysregulation disorder, persistent irritability, temper outbursts 

  15. Status of the segment interconnect, cable segment ancillary logic, and the cable segment hybrid driver projects

    International Nuclear Information System (INIS)

    Swoboda, C.; Barsotti, E.; Chappa, S.; Downing, R.; Goeransson, G.; Lensy, D.; Moore, G.; Rotolo, C.; Urish, J.

    1985-01-01

    The FASTBUS Segment Interconnect (SI) provides a communication path between two otherwise independent, asynchronous bus segments. In particular, the Segment Interconnect links a backplane crate segment to a cable segment. All standard FASTBUS address and data transactions can be passed through the SI or any number of SIs and segments in a path. Thus systems of arbitrary connection complexity can be formed, allowing simultaneous independent processing, yet still permitting devices associated with one segment to be accessed from others. The model S1 Segment Interconnect and the Cable Segment Ancillary Logic covered in this report comply with all the mandatory features stated in the FASTBUS specification document DOE/ER-0189. A block diagram of the SI is shown

  16. Segmental Vitiligo.

    Science.gov (United States)

    van Geel, Nanja; Speeckaert, Reinhart

    2017-04-01

    Segmental vitiligo is characterized by its early onset, rapid stabilization, and unilateral distribution. Recent evidence suggests that segmental and nonsegmental vitiligo could represent variants of the same disease spectrum. Observational studies with respect to its distribution pattern point to a possible role of cutaneous mosaicism, whereas the original stated dermatomal distribution seems to be a misnomer. Although the exact pathogenic mechanism behind the melanocyte destruction is still unknown, increasing evidence has been published on the autoimmune/inflammatory theory of segmental vitiligo. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Cytosine methylation dysregulation in neonates following intrauterine growth restriction.

    Directory of Open Access Journals (Sweden)

    Francine Einstein

    2010-01-01

    Full Text Available Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g., type 2 diabetes mellitus; T2DM, manifesting as late as decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations, and focused our studies specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood from neonates with intrauterine growth restriction (IUGR and control subjects.Our epigenomic assays utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to IUGR of moderate degree and involving a restricted number of loci. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4alpha (HNF4A gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins.Our results give insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease.

  18. Cytosine Methylation Dysregulation in Neonates Following Intrauterine Growth Restriction

    Science.gov (United States)

    Bhagat, Tushar D.; Fazzari, Melissa J.; Verma, Amit; Barzilai, Nir; Greally, John M.

    2010-01-01

    Background Perturbations of the intrauterine environment can affect fetal development during critical periods of plasticity, and can increase susceptibility to a number of age-related diseases (e.g., type 2 diabetes mellitus; T2DM), manifesting as late as decades later. We hypothesized that this biological memory is mediated by permanent alterations of the epigenome in stem cell populations, and focused our studies specifically on DNA methylation in CD34+ hematopoietic stem and progenitor cells from cord blood from neonates with intrauterine growth restriction (IUGR) and control subjects. Methods and Findings Our epigenomic assays utilized a two-stage design involving genome-wide discovery followed by quantitative, single-locus validation. We found that changes in cytosine methylation occur in response to IUGR of moderate degree and involving a restricted number of loci. We also identify specific loci that are targeted for dysregulation of DNA methylation, in particular the hepatocyte nuclear factor 4α (HNF4A) gene, a well-known diabetes candidate gene not previously associated with growth restriction in utero, and other loci encoding HNF4A-interacting proteins. Conclusions Our results give insights into the potential contribution of epigenomic dysregulation in mediating the long-term consequences of IUGR, and demonstrate the value of this approach to studies of the fetal origin of adult disease. PMID:20126273

  19. Detection of nearest neighbors to specific fluorescently tagged ligands in rod outer segment and lymphocyte plasma membranes by photosensitization of 5-iodonaphthyl 1-azide

    International Nuclear Information System (INIS)

    Raviv, Y.; Bercovici, T.; Gitler, C.; Salomon, Y.

    1989-01-01

    Lima bean agglutinin-fluorescein 5-isothiocyanate conjugate (FluNCS-lima bean lectin) interacts with specific receptor molecules on membranes both from the rod outer segment (ROS) of the frog retina and from S49 mouse lymphoma cells. When [125I]-5-iodonaphthyl 1-azide (125I-INA), which freely and randomly partitions into the lipid bilayer, is added to membranes and the suspension is irradiated at 480 nm, the FluNCS-conjugated lectin photosensitizes the [125I]INA but only at discrete sites. This results in the selective labeling of specific proteins: an 88-kDa protein on ROS membranes and a 56-kDa protein on S49 plasma membranes. Labeling is dependent upon the interaction of the FluNCS-lectin with glycosylated receptor sites, since N-acetylgalactosamine, but not methyl alpha-mannoside, blocked labeling of the 56-kDa protein on S49 membranes. In contrast, a random labeling pattern of membrane proteins was observed upon irradiation at 480 nm using other fluorescein conjugates, such as FluNCS-bovine serum albumin (FluNCS-BSA) or FluNCS-soybean trypsin inhibitor (FluNCS-STI), which interact with cell membranes in a nonselective manner, or with N-(fluorescein-5-thiocarbamoyl)-n-undecyclamine (FluNCS-NHC11), which is freely miscible in the membrane lipid. Random labeling was also obtained by direct photoexcitation of [125I]INA at 314 nm, with no distinct labeling of the 88- and 56-kDa proteins in the respective membranes. These results suggest that protein ligands can be used to guide sensitizers to discrete receptor sites and lead to their selective labeling by photosensitized activation of [125I]INA

  20. Questioned validity of Gene Expression Dysregulated Domains in Down's Syndrome [v1; ref status: indexed, http://f1000r.es/5ky

    Directory of Open Access Journals (Sweden)

    Long H. Do

    2015-07-01

    Full Text Available Recently, in studies examining fibroblasts obtained from the tissues of one set of monozygotic twins (i.e. fetuses derived from the same egg discordant for trisomy 21 (Down syndrome; DS, Letourneau et al., reported the presence of a defined pattern of dysregulation within specific genomic domains they referred to as Gene Expression Dysregulated Domains (GEDDs. GEDDs were described as alternating segments of increased or decreased gene expression affecting all chromosomes. Strikingly, GEDDs in fibroblasts were largely conserved in induced pluripotent cells (iPSCs generated from the twin’s fibroblasts as well as in fibroblasts from the Ts65Dn mouse model of DS. Our recent analysis failed to find GEDDs. We reexamined the human iPSCs RNAseq data from Letourneau et al., and data from this same research group published earlier examining iPSCs from the same monozygotic twins. An independent analysis of RNAseq data from Ts65Dn fibroblasts also failed to confirm presence of GEDDs. Our analysis questions the validity of GEDDs in DS.

  1. The effectiveness of endobronchial therapy in patients with chemo-resistant tuberculosis when specific process is localized in the lungs apical segments

    Directory of Open Access Journals (Sweden)

    V. M. Khlystun

    2017-08-01

    Full Text Available Objective – to study the effectiveness of the additional methods of endobronchial pathology treatment in patients with chemo-resistant tuberculosis (CRTB of lungs, that aimed to treat a specific process in bronchi when destructions are localized in the apical segments (S1+2 of lungs. Materials and methods. In order to investigate effectiveness of the additional methods of endobronchial pathology treatment of bronchial mucosa 79 patients with CRTB of lungs were examined. They were divided into 3 groups: basic 1 group, which included 27 patients who were treated by using antimycobacterial drugs endobronchial introduction to S1+2 with further implementation of intraorganic electrophoresis in S1+2 zone in combination with systemic receiving of antimycobacterial drugs; the comparison basic 2 group 27 patients who were treated with systemic antimycobacterial therapy in combination with antituberculosis drugs inhalations; and the group included – 25 patients who received only systemic antimycobacterial therapy. Groups were compared by the severity of the process, age and gender. Tracheobronchial tree fiber-bronchoscopy in patients with CRTB of lungs was carried out on the basis of phthisiology and pulmonology department of ZSMU in communal institution "Zaporizhzhia regional antituberculosis dispensary", by the author on their own. Character of bronchial mucosa was examined under anesthesia by fiber-bronchoscopes of company "Olympus" (Japan. Bronchial tree pathology was described according to N. V. Shesterynoy, A. N. Kaliuk (1975 classification. Results of the study were processed with modern methods of analysis on a personal computer with using the Statistical Package license software Statistica® for Windows 6.0 (StatSoft Inc., № AXXR712 D833214FAN5. Results. The use of antimycobacterial drugs endobronchial introduction to S1+2 with further implementation of intraorganic electrophoresis in S1+2 zone contributed significantly increase the

  2. Endocrine Dysregulation in Anorexia Nervosa Update

    Science.gov (United States)

    2011-01-01

    Context: Anorexia nervosa is a primary psychiatric disorder with serious endocrine consequences, including dysregulation of the gonadal, adrenal, and GH axes, and severe bone loss. This Update reviews recent advances in the understanding of the endocrine dysregulation observed in this state of chronic starvation, as well as the mechanisms underlying the disease itself. Evidence Acquisition: Findings of this update are based on a PubMed search and the author's knowledge of this field. Evidence Synthesis: Recent studies have provided insights into the mechanisms underlying endocrine dysregulation in states of chronic starvation as well as the etiology of anorexia nervosa itself. This includes a more complex understanding of the pathophysiologic bases of hypogonadism, hypercortisolemia, GH resistance, appetite regulation, and bone loss. Nevertheless, the etiology of the disease remains largely unknown, and effective therapies for the endocrine complications and for the disease itself are lacking. Conclusions: Despite significant progress in the field, further research is needed to elucidate the mechanisms underlying the development of anorexia nervosa and its endocrine complications. Such investigations promise to yield important advances in the therapeutic approach to this disease as well as to the understanding of the regulation of endocrine function, skeletal biology, and appetite regulation. PMID:21976742

  3. SI-SHY: Dysregulated Fear in Toddlerhood Predicts Kindergarten Social Withdrawal through Protective Parenting.

    Science.gov (United States)

    Kiel, Elizabeth J; Buss, Kristin A

    2014-05-01

    Two recent advances in the study of fearful temperament (behavioral inhibition) include the validation of dysregulated fear as a temperamental construct that more specifically predicts later social withdrawal and anxiety, and the use of conceptual and statistical models that place parenting as a mechanism of development from temperament to these outcomes. The current study further advances these areas by examining whether protective parenting mediated the relation between dysregulated fear in toddlerhood and social withdrawal in kindergarten. Participants included 93 toddlers and their mothers, who engaged in laboratory tasks assessing traditional fearful temperament, dysregulated fear, and protective parenting. When children reached kindergarten, they returned to the laboratory for a multimethod assessment of social withdrawal. Results confirmed the hypothesis that dysregulated fear predicted social withdrawal through protective parenting, and this occurred above and beyond the effect of traditional fearful temperament. These findings bolster support for the use of dysregulated fear as a temperamental construct related to, but perhaps more discerning of risk than traditionally measured fearful temperament/behavioral inhibition and highlight the importance of transactional influences between the individual and the caregiving environment in the development of social withdrawal.

  4. Emotion dysregulation mediates the relationship between child maltreatment and psychopathology: A structural equation model.

    Science.gov (United States)

    Jennissen, Simone; Holl, Julia; Mai, Hannah; Wolff, Sebastian; Barnow, Sven

    2016-12-01

    The present study investigated the mediating effects of emotion dysregulation on the relationship between child maltreatment and psychopathology. An adult sample (N=701) from diverse backgrounds of psychopathology completed the Childhood Trauma Questionnaire (CTQ), the Difficulties in Emotion Regulation Scale (DERS), the Brief Symptom Inventory (BSI), and the negative affect subscale of the Positive and Negative Affect Schedule (PANAS) in a cross-sectional online survey. Correlational analyses showed that all types of child maltreatment were uniformly associated with emotion dysregulation, and dimensions of emotion dysregulation were strongly related to psychopathology. Limited access to strategies for emotion regulation emerged as the most powerful predictor. Structural equation modeling analyses revealed that emotion dysregulation partially mediated the relationship between child maltreatment and psychopathology, even after controlling for shared variance with negative affect. These findings emphasize the importance of emotion dysregulation as a possible mediating mechanism in the association between child maltreatment and later psychopathology. Additionally, interventions targeting specific emotion regulation strategies may be effective to reduce psychopathology in victims of child maltreatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. SI-SHY: Dysregulated Fear in Toddlerhood Predicts Kindergarten Social Withdrawal through Protective Parenting

    Science.gov (United States)

    Kiel, Elizabeth J.; Buss, Kristin A.

    2014-01-01

    Two recent advances in the study of fearful temperament (behavioral inhibition) include the validation of dysregulated fear as a temperamental construct that more specifically predicts later social withdrawal and anxiety, and the use of conceptual and statistical models that place parenting as a mechanism of development from temperament to these outcomes. The current study further advances these areas by examining whether protective parenting mediated the relation between dysregulated fear in toddlerhood and social withdrawal in kindergarten. Participants included 93 toddlers and their mothers, who engaged in laboratory tasks assessing traditional fearful temperament, dysregulated fear, and protective parenting. When children reached kindergarten, they returned to the laboratory for a multimethod assessment of social withdrawal. Results confirmed the hypothesis that dysregulated fear predicted social withdrawal through protective parenting, and this occurred above and beyond the effect of traditional fearful temperament. These findings bolster support for the use of dysregulated fear as a temperamental construct related to, but perhaps more discerning of risk than traditionally measured fearful temperament/behavioral inhibition and highlight the importance of transactional influences between the individual and the caregiving environment in the development of social withdrawal. PMID:25242893

  6. Effect of sedentary behaviour and vigorous physical activity on segment-specific carotid wall thickness and its progression in a healthy population.

    LENUS (Irish Health Repository)

    2010-06-01

    This study investigated whether sedentary behaviour and different activity levels have an independent association with carotid intima-media thickness (IMT) and with the 3-year IMT progression in different carotid segments.

  7. International EUREKA: Initialization Segment

    International Nuclear Information System (INIS)

    1982-02-01

    The Initialization Segment creates the starting description of the uranium market. The starting description includes the international boundaries of trade, the geologic provinces, resources, reserves, production, uranium demand forecasts, and existing market transactions. The Initialization Segment is designed to accept information of various degrees of detail, depending on what is known about each region. It must transform this information into a specific data structure required by the Market Segment of the model, filling in gaps in the information through a predetermined sequence of defaults and built in assumptions. A principal function of the Initialization Segment is to create diagnostic messages indicating any inconsistencies in data and explaining which assumptions were used to organize the data base. This permits the user to manipulate the data base until such time the user is satisfied that all the assumptions used are reasonable and that any inconsistencies are resolved in a satisfactory manner

  8. Dysregulated Fear in Toddlerhood Predicts Kindergarten Social Withdrawal through Protective Parenting

    Science.gov (United States)

    Kiel, Elizabeth J.; Buss, Kristin A.

    2014-01-01

    Two recent advances in the study of fearful temperament (behavioural inhibition) include the validation of dysregulated fear as a temperamental construct that more specifically predicts later social withdrawal and anxiety, and the use of conceptual and statistical models that place parenting as a mechanism of development from temperament to these…

  9. Identification and differentiation of the twenty six bluetongue virus serotypes by RT-PCR amplification of the serotype-specific genome segment 2.

    Directory of Open Access Journals (Sweden)

    Narender S Maan

    Full Text Available Bluetongue (BT is an arthropod-borne viral disease, which primarily affects ruminants in tropical and temperate regions of the world. Twenty six bluetongue virus (BTV serotypes have been recognised worldwide, including nine from Europe and fifteen in the United States. Identification of BTV serotype is important for vaccination programmes and for BTV epidemiology studies. Traditional typing methods (virus isolation and serum or virus neutralisation tests (SNT or VNT are slow (taking weeks, depend on availability of reference virus-strains or antisera and can be inconclusive. Nucleotide sequence analyses and phylogenetic comparisons of genome segment 2 (Seg-2 encoding BTV outer-capsid protein VP2 (the primary determinant of virus serotype were completed for reference strains of BTV-1 to 26, as well as multiple additional isolates from different geographic and temporal origins. The resulting Seg-2 database has been used to develop rapid (within 24 h and reliable RT-PCR-based typing assays for each BTV type. Multiple primer-pairs (at least three designed for each serotype were widely tested, providing an initial identification of serotype by amplification of a cDNA product of the expected size. Serotype was confirmed by sequencing of the cDNA amplicons and phylogenetic comparisons to previously characterised reference strains. The results from RT-PCR and sequencing were in perfect agreement with VNT for reference strains of all 26 BTV serotypes, as well as the field isolates tested. The serotype-specific primers showed no cross-amplification with reference strains of the remaining 25 serotypes, or multiple other isolates of the more closely related heterologous BTV types. The primers and RT-PCR assays developed in this study provide a rapid, sensitive and reliable method for the identification and differentiation of the twenty-six BTV serotypes, and will be updated periodically to maintain their relevance to current BTV distribution and

  10. The effects of early positive parenting and developmental delay status on child emotion dysregulation.

    Science.gov (United States)

    Norona, A N; Baker, B L

    2017-02-01

    Emotion regulation has been identified as a robust predictor of adaptive functioning across a variety of domains (Aldao et al. ). Furthermore, research examining early predictors of competence and deficits in ER suggests that factors internal to the individual (e.g. neuroregulatory reactivity, behavioural traits and cognitive ability) and external to the individual (e.g. caregiving styles and explicit ER training) contribute to the development of ER (Calkins ). Many studies have focused on internal sources or external sources; however, few have studied them simultaneously within one model, especially in studies examining children with developmental delays (DD). Here, we addressed this specific research gap and examined the contributions of one internal factor and one external factor on emotion dysregulation outcomes in middle childhood. Specifically, our current study used structural equation modelling (SEM) to examine prospective, predictive relationships between DD status, positive parenting at age 4 years and child emotion dysregulation at age 7 years. Participants were 151 families in the Collaborative Family Study, a longitudinal study of young children with and without DD. A positive parenting factor was composed of sensitivity and scaffolding scores from mother-child interactions at home and in the research centre at child age 4 years. A child dysregulation factor was composed of a dysregulation code from mother-child interactions and a parent-report measure of ER and lability/negativity at age 7 years. Finally, we tested the hypothesis that positive parenting would mediate the relationship between DD and child dysregulation. Mothers of children with DD exhibited fewer sensitive and scaffolding behaviours compared with mothers of typically developing children, and children with DD were more dysregulated on all measures of ER. SEM revealed that both DD status and early positive parenting predicted emotion dysregulation in middle childhood. Furthermore

  11. Mixed segmentation

    DEFF Research Database (Denmark)

    Hansen, Allan Grutt; Bonde, Anders; Aagaard, Morten

    content analysis and audience segmentation in a single-source perspective. The aim is to explain and understand target groups in relation to, on the one hand, emotional response to commercials or other forms of audio-visual communication and, on the other hand, living preferences and personality traits...

  12. Advantage of whole exome sequencing over allele-specific and targeted segment sequencing in detection of novel TULP1 mutation in leber congenital amaurosis

    DEFF Research Database (Denmark)

    Guo, Yiran; Prokudin, Ivan; Yu, Cong

    2015-01-01

    by targeted segment sequencing of 61 regions in 14 causative genes was performed. Subsequently, exome sequencing was undertaken in the proband, unaffected consanguineous parents and two unaffected siblings. Bioinformatic analysis used two independent pipelines, BWA-GATK and SOAP, followed by Annovar and Snp...

  13. Dysregulation of RNA Mediated Gene Expression in Motor Neuron Diseases.

    Science.gov (United States)

    Gonçalves, Inês do Carmo G; Rehorst, Wiebke A; Kye, Min Jeong

    2016-01-01

    Recent findings indicate an important role for RNA-mediated gene expression in motor neuron diseases, including ALS (amyotrophic lateral sclerosis) and SMA (spinal muscular atrophy). ALS, also known as Lou Gehrig's disease, is an adult-onset progressive neurodegenerative disorder, whereby SMA or "children's Lou Gehrig's disease" is considered a pediatric neurodevelopmental disorder. Despite the difference in genetic causes, both ALS and SMA share common phenotypes; dysfunction/loss of motor neurons that eventually leads to muscle weakness and atrophy. With advanced techniques in molecular genetics and cell biology, current data suggest that these two distinct motor neuron diseases share more than phenotypes; ALS and SMA have similar cellular pathological mechanisms including mitochondrial dysfunction, oxidative stress and dysregulation in RNA-mediated gene expression. Here, we will discuss the current findings on these two diseases with specific focus on RNA-mediated gene regulation including miRNA expression, pre-mRNA processing and RNA binding proteins.

  14. MicroRNA regulation and dysregulation in epilepsy

    Directory of Open Access Journals (Sweden)

    Danyella Barbosa Dogini

    2013-10-01

    Full Text Available Epilepsy, one of the most frequent neurological disorders, represents a group of diseases that have in common the clinical occurrence of seizures. The pathogenesis of different types of epilepsy involves many important biological pathways; some of which have been shown to be regulated by microRNAs (miRNAs. In this paper, we will critically review relevant studies regarding the role of miRNAs in epilepsy. Overall, the most common type of epilepsy in the adult population is temporal lobe epilepsy (TLE, and the form associated with mesial temporal sclerosis (MTS, called mesial TLE, is particularly relevant due to the high frequency of resistance to clinical treatment. There are several target studies, as well few genome-wide miRNA expression profiling studies reporting abnormal miRNA expression in tissue with MTS, both in patients and in animal models. Overall, these studies show a fine correlation between miRNA regulation/dysregulation and inflammation, seizure-induced neuronal death and other relevant biological pathways. Furthermore, expression of many miRNAs is dynamically regulated during neurogenesis and its dysregulation may play a role in the process of cerebral corticogenesis leading to malformations of cortical development (MCD, which represent one of the major causes of drug-resistant epilepsy. In addition, there are reports of miRNAs involved in cell proliferation, fate specification and neuronal maturation and these processes are tightly linked to the pathogenesis of MCD. Large-scale analyzes of miRNA expression in animal models with induced status epilepticus have demonstrated changes in a selected group of miRNAs thought to be involved in the regulation of cell death, synaptic reorganization, neuroinflammation and neural excitability. In addition, knocking-down specific miRNAs in these animals have demonstrated that this may consist in a promising therapeutic intervention.

  15. Anxiety among adults with a history of childhood adversity: Psychological resilience moderates the indirect effect of emotion dysregulation.

    Science.gov (United States)

    Poole, Julia C; Dobson, Keith S; Pusch, Dennis

    2017-08-01

    Adverse childhood experiences (ACEs) have been widely identified as risk factors for increased symptoms of anxiety across the lifespan. Little is known, however, about the processes by which ACEs set the stage for increased symptoms of anxiety in adulthood. The current study evaluated whether emotion dysregulation and psychological resilience influence the association between ACEs and symptoms of anxiety. A sample of adult primary care patients (N=4006) completed self-report measures related to ACEs, symptoms of anxiety, emotion dysregulation, and psychological resilience. A moderated mediation analysis showed that emotion dysregulation mediated the association between ACEs and anxiety symptoms, and that the strength of this effect varied as a function of psychological resilience. Specifically, the influence of ACEs on emotional dysregulation was stronger among individuals with low levels of psychological resilience than among those with high levels of psychological resilience. These findings remained significant when controlling for a range of sociodemographic variables in the model. Cross-sectional designs preclude inferences about causality and self-report data may be susceptible to reporting biases. Other psychological variables that may be relevant to the current results, such as protective factors in childhood, were not assessed. These results have implications for the conceptualization of ACEs, emotion dysregulation, and psychological resilience in etiological models of anxiety. They also highlight the relevance of ACEs, emotion dysregulation, and psychological resilience to the detection, treatment, and prevention of anxiety disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  16. Connecting textual segments

    DEFF Research Database (Denmark)

    Brügger, Niels

    2017-01-01

    history than just the years of the emergence of the web, the chapter traces the history of how segments of text have deliberately been connected to each other by the use of specific textual and media features, from clay tablets, manuscripts on parchment, and print, among others, to hyperlinks on stand......In “Connecting textual segments: A brief history of the web hyperlink” Niels Brügger investigates the history of one of the most fundamental features of the web: the hyperlink. Based on the argument that the web hyperlink is best understood if it is seen as another step in a much longer and broader...

  17. Automated medical image segmentation techniques

    Directory of Open Access Journals (Sweden)

    Sharma Neeraj

    2010-01-01

    Full Text Available Accurate segmentation of medical images is a key step in contouring during radiotherapy planning. Computed topography (CT and Magnetic resonance (MR imaging are the most widely used radiographic techniques in diagnosis, clinical studies and treatment planning. This review provides details of automated segmentation methods, specifically discussed in the context of CT and MR images. The motive is to discuss the problems encountered in segmentation of CT and MR images, and the relative merits and limitations of methods currently available for segmentation of medical images.

  18. Emotion Dysregulation and Adolescent Psychopathology: A Prospective Study

    Science.gov (United States)

    Hatzenbuehler, Mark L.; Nolen-Hoeksema, Susan

    2011-01-01

    Background Emotion regulation deficits have been consistently linked to psychopathology in cross-sectional studies. However, the direction of the relationship between emotion regulation and psychopathology is unclear. This study examined the longitudinal and reciprocal relationships between emotion regulation deficits and psychopathology in adolescents. Methods Emotion dysregulation and symptomatology (depression, anxiety, aggressive behavior, and eating pathology) were assessed in a large, diverse sample of adolescents (N = 1,065) at two time points separated by seven months. Structural equation modeling was used to examine the longitudinal and reciprocal relationships between emotion dysregulation and symptoms of psychopathology. Results The three distinct emotion processes examined here (emotional understanding, dysregulated expression of sadness and anger, and ruminative responses to distress) formed a unitary latent emotion dysregulation factor. Emotion dysregulation predicted increases in anxiety symptoms, aggressive behavior, and eating pathology after controlling for baseline symptoms but did not predict depressive symptoms. In contrast, none of the four types of psychopathology predicted increases in emotion dysregulation after controlling for baseline emotion dysregulation. Conclusions Emotion dysregulation appears to be an important transdiagnostic factor that increases risk for a wide range of psychopathology outcomes in adolescence. These results suggest targets for preventive interventions during this developmental period of risk. PMID:21718967

  19. Adverse Childhood Experiences and Disordered Gambling: Assessing the Mediating Role of Emotion Dysregulation.

    Science.gov (United States)

    Poole, Julia C; Kim, Hyoun S; Dobson, Keith S; Hodgins, David C

    2017-12-01

    Adverse childhood experiences (ACEs), such as sexual and physical abuse, have been established as risk factors for the development of disordered gambling. The underlying mechanism by which ACEs influence disordered gambling, however, remains unknown. The aims of the present research were to comprehensively investigate ten types of childhood adversity and their relationships to disordered gambling in adulthood, and to test whether emotion dysregulation mediated the relationship between ACEs and disordered gambling. A sample of community gamblers (N = 414) completed self-report measures of ACEs, emotion dysregulation, and gambling severity. Results revealed a significant association between all but one type (physical abuse) of ACEs and disordered gambling. Further, the results highlighted the cumulative impact of ACEs on gambling. Specifically, individuals who experienced three or more types of ACEs were more than three times as likely to report disordered gambling as compared to individuals with no history of childhood adversity. Importantly, as hypothesized, emotion dysregulation mediated the relationship between ACEs and disordered gambling. Findings from this research describe the association between ACEs and gambling and indicate a causal link between childhood adversity and disordered gambling. Results suggest that treatment initiatives may do well to address both ACEs and emotion dysregulation in the treatment of problem gambling.

  20. Childhood trauma and eating psychopathology: a mediating role for dissociation and emotion dysregulation?

    Science.gov (United States)

    Moulton, Stuart J; Newman, Emily; Power, Kevin; Swanson, Vivien; Day, Kenny

    2015-01-01

    The present study examined the relationship between different forms of childhood trauma and eating psychopathology using a multiple mediation model that included emotion dysregulation and dissociation as hypothesised mediators. 142 female undergraduate psychology students studying at two British Universities participated in this cross-sectional study. Participants completed measures of childhood trauma (emotional abuse, physical abuse, sexual abuse, emotional neglect and physical neglect), eating psychopathology, dissociation and emotion dysregulation. Multiple mediation analysis was conducted to investigate the study's proposed model. Results revealed that the multiple mediation model significantly predicted eating psychopathology. Additionally, both emotion dysregulation and dissociation were found to be significant mediators between childhood trauma and eating psychopathology. A specific indirect effect was observed between childhood emotional abuse and eating psychopathology through emotion dysregulation. Findings support previous research linking childhood trauma to eating psychopathology. They indicate that multiple forms of childhood trauma should be assessed for individuals with eating disorders. The possible maintaining role of emotion regulation processes should also be considered in the treatment of eating disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. How Parkinsonian Toxins Dysregulate the Autophagy Machinery

    Directory of Open Access Journals (Sweden)

    Ruben K. Dagda

    2013-11-01

    Full Text Available Since their discovery, Parkinsonian toxins (6-hydroxydopamine, MPP+, paraquat, and rotenone have been widely employed as in vivo and in vitro chemical models of Parkinson’s disease (PD. Alterations in mitochondrial homeostasis, protein quality control pathways, and more recently, autophagy/mitophagy have been implicated in neurotoxin models of PD. Here, we highlight the molecular mechanisms by which different PD toxins dysregulate autophagy/mitophagy and how alterations of these pathways play beneficial or detrimental roles in dopamine neurons. The convergent and divergent effects of PD toxins on mitochondrial function and autophagy/mitophagy are also discussed in this review. Furthermore, we propose new diagnostic tools and discuss how pharmacological modulators of autophagy/mitophagy can be developed as disease-modifying treatments for PD. Finally, we discuss the critical need to identify endogenous and synthetic forms of PD toxins and develop efficient health preventive programs to mitigate the risk of developing PD.

  2. Steroid dysregulation and stomatodynia (burning mouth syndrome).

    Science.gov (United States)

    Woda, Alain; Dao, Thuan; Gremeau-Richard, Christelle

    2009-01-01

    Stomatodynia ( burning mouth syndrome) is characterized by a spontaneous, continuous burning pain felt in the oral mucosa typically of anxiodepressive menopausal women. Because there is no obvious organic cause, it is considered a nonspecific pain. This Focus Article proposes a hypothesis based on the following pathophysiological cascade: chronic anxiety or post traumatic stress leads to a dysregulation of the adrenal production of steroids. One consequence is a decreased or modified production of some major precursors for the neuroactive steroid synthesis occurring in the skin, mucosa, and nervous system. At menopause, the drastic fall of the other main precursor supply , the gonadal steroids, leads to a brisk alteration of the production of neuroactive steroids. This results in neurodegenerative alterations of small nerves fibers of the oral mucosa and /or some brain areas involved in oral somatic sensations. These neuropathic changes become irreversible and precipitate the burning pain, dysgeusia, and xerostomia associated with stomatodynia, which all involve thin nerve fibers.

  3. Brookhaven segment interconnect

    International Nuclear Information System (INIS)

    Morse, W.M.; Benenson, G.; Leipuner, L.B.

    1983-01-01

    We have performed a high energy physics experiment using a multisegment Brookhaven FASTBUS system. The system was composed of three crate segments and two cable segments. We discuss the segment interconnect module which permits communication between the various segments

  4. PTSD Symptoms, Emotion Dysregulation, and Alcohol-Related Consequences Among College Students With a Trauma History.

    Science.gov (United States)

    Tripp, Jessica C; McDevitt-Murphy, Meghan E; Avery, Megan L; Bracken, Katherine L

    2015-01-01

    gender, impulse control difficulties remained a mediator for men and difficulties engaging in goal directed behavior for women. These analyses shed light on processes that may underlie "self-medication" of PTSD symptoms. Gender-specific interventions targeting emotion dysregulation may be effective in reducing alcohol-related consequences in individuals with PTSD. Women may possibly benefit from interventions that focus on difficulties engaging in goal-directed behavior, while men may benefit from interventions that target impulse control difficulties when upset.

  5. The Relationship between Childhood Maltreatment and Emotional Dysregulation in Self Mutilation: An Investigation among Substance Dependent Patients.

    Science.gov (United States)

    Karagöz, Başak; Dağ, İhsan

    2015-03-01

    The present study aims to examine the role of emotion dysregulation and childhood maltreatment in self mutilation (SM) of substance dependent patients. Specifically, the present study examined whether emotion dysregulation and its dimensions, and childhood maltreatment and its dimensions were associated with SM. The relationship between emotion dysregulation and childhood maltreatment was also investigated. The sample of study consisted of 55 alcohol dependent and 24 opiate dependent patients (n=79). Substance dependence was diagnosed by means of the Structured Clinical Interview for DSM-IV-TR (SCID-I), Turkish version. Childhood Trauma Questionnaire (CTQ) and Difficulties in Emotion Regulation Scale (DERS) were used. Findings indicated that substance dependents with SM and without SM were differentiated in terms of overall emotion dysregulation. Results also suggest the relevance of three specific dimensions of emotion dysregulation to SM: Difficulties engaging in goal-directed behaviors when experiencing negative emotions, difficulties controlling impulsive behaviors when experiencing negative emotions, and limited access to effective emotion regulation strategies. These dimensions were predicted from childhood emotional maltreatment and neglect. It is also revealed that substance dependents with SM had higher points than those without SM on emotional childhood maltreatment and neglect, physical childhood maltreatment. Results were supported by the literature suggested that self-mutilation functions as a emotional regulation strategy. Findings also suggested that self- mutilation is related to early relationships take place in family environment in which individuals grow up.

  6. Identifying microRNA/mRNA dysregulations in ovarian cancer.

    Science.gov (United States)

    Miles, Gregory D; Seiler, Michael; Rodriguez, Lorna; Rajagopal, Gunaretnam; Bhanot, Gyan

    2012-03-27

    MicroRNAs are a class of noncoding RNA molecules that co-regulate the expression of multiple genes via mRNA transcript degradation or translation inhibition. Since they often target entire pathways, they may be better drug targets than genes or proteins. MicroRNAs are known to be dysregulated in many tumours and associated with aggressive or poor prognosis phenotypes. Since they regulate mRNA in a tissue specific manner, their functional mRNA targets are poorly understood. In previous work, we developed a method to identify direct mRNA targets of microRNA using patient matched microRNA/mRNA expression data using an anti-correlation signature. This method, applied to clear cell Renal Cell Carcinoma (ccRCC), revealed many new regulatory pathways compromised in ccRCC. In the present paper, we apply this method to identify dysregulated microRNA/mRNA mechanisms in ovarian cancer using data from The Cancer Genome Atlas (TCGA). TCGA Microarray data was normalized and samples whose class labels (tumour or normal) were ambiguous with respect to consensus ensemble K-Means clustering were removed. Significantly anti-correlated and correlated genes/microRNA differentially expressed between tumour and normal samples were identified. TargetScan was used to identify gene targets of microRNA. We identified novel microRNA/mRNA mechanisms in ovarian cancer. For example, the expression level of RAD51AP1 was found to be strongly anti-correlated with the expression of hsa-miR-140-3p, which was significantly down-regulated in the tumour samples. The anti-correlation signature was present separately in the tumour and normal samples, suggesting a direct causal dysregulation of RAD51AP1 by hsa-miR-140-3p in the ovary. Other pairs of potentially biological relevance include: hsa-miR-145/E2F3, hsa-miR-139-5p/TOP2A, and hsa-miR-133a/GCLC. We also identified sets of positively correlated microRNA/mRNA pairs that are most likely result from indirect regulatory mechanisms. Our findings identify

  7. Dissociative symptoms and neuroendocrine dysregulation in depression.

    Science.gov (United States)

    Bob, Petr; Fedor-Freybergh, Peter; Jasova, Denisa; Bizik, Gustav; Susta, Marek; Pavlat, Josef; Zima, Tomas; Benakova, Hana; Raboch, Jiri

    2008-10-01

    Dissociative symptoms are traditionally attributed to psychological stressors that produce dissociated memories related to stressful life events. Dissociative disorders and dissociative symptoms including psychogenic amnesia, fugue, dissociative identity-disorder, depersonalization, derealization and other symptoms or syndromes have been reported as an epidemic psychiatric condition that may be coexistent with various psychiatric diagnoses such as depression, schizophrenia, borderline personality disorder or anxiety disorders. According to recent findings also the somatic components of dissociation may occur and influence brain, autonomic and neuroendocrine functions. At this time there are only few studies examining neuroendocrine response related to dissociative symptoms that suggest significant dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis. The aim of the present study is to perform examination of HPA axis functioning indexed by basal cortisol and prolactin and test their relationship to psychic and somatoform dissociative symptoms. Basal cortisol and prolactin and psychic and somatoform dissociative symptoms were assessed in 40 consecutive inpatients with diagnosis of unipolar depression mean age 43.37 (SD=12.21). The results show that prolactin and cortisol as indices of HPA axis functioning manifest significant relationship to dissociative symptoms. Main results represent highly significant correlations obtained by simple regression between psychic dissociative symptoms (DES) and serum prolactin (R=0.55, p=0.00027), and between somatoform dissociation (SDQ-20) and serum cortisol (R=-0.38, p=0.015). These results indicate relationship between HPA-axis reactivity and dissociative symptoms in unipolar depressive patients that could reflect passive coping behavior and disengagement.

  8. Confabulation: Developing the 'emotion dysregulation' hypothesis.

    Science.gov (United States)

    Turnbull, Oliver H; Salas, Christian E

    2017-02-01

    Confabulations offer unique opportunities for establishing the neurobiological basis of delusional thinking. As regards causal factors, a review of the confabulation literature suggests that neither amnesia nor executive impairment can be the sole (or perhaps even the primary) cause of all delusional beliefs - though they may act in concert with other factors. A key perspective in the modern literature is that many delusions have an emotionally positive or 'wishful' element, that may serve to modulate or manage emotional experience. Some authors have referred to this perspective as the 'emotion dysregulation' hypothesis. In this article we review the theoretical underpinnings of this approach, and develop the idea by suggesting that the positive aspects of confabulatory states may have a role in perpetuating the imbalance between cognitive control and emotion. We draw on existing evidence from fields outside neuropsychology, to argue for three main causal factors: that positive emotions are related to more global or schematic forms of cognitive processing; that positive emotions influence the accuracy of memory recollection; and that positive emotions make people more susceptible to false memories. These findings suggest that the emotions that we want to feel (or do not want to feel) can influence the way we reconstruct past experiences and generate a sense of self - a proposition that bears on a unified theory of delusional belief states. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

  9. Dopaminergic Dysregulation, Artistic Expressiveness, and Parkinson's Disease

    Science.gov (United States)

    López-Pousa, S.; Lombardía-Fernández, C.; Olmo, J. Garre; Monserrat-Vila, S.; Vilalta-Franch, J.; Calvó-Perxas, L.

    2012-01-01

    Background The most frequent behavioral manifestations in Parkinson's disease (PD) are attributed to the dopaminergic dysregulation syndrome (DDS), which is considered to be secondary to the iatrogenic effects of the drugs that replace dopamine. Over the past few years some cases of patients improving their creative abilities after starting treatment with dopaminergic pharmaceuticals have been reported. These effects have not been clearly associated to DDS, but a relationship has been pointed out. Methods Case study of a patient with PD. The evolution of her paintings along medication changes and disease advance has been analyzed. Results The patient showed a compulsive increase of pictorial production after the diagnosis of PD was made. She made her best paintings when treated with cabergolide, and while painting, she reported a feeling of well-being, with loss of awareness of the disease and reduction of physical limitations. Conclusions Dopaminergic antagonists (DA) trigger a dopaminergic dysfunction that alters artistic creativity in patients having a predisposition for it. The development of these skills might be due to the dopaminergic overstimulation due to the therapy with DA, which causes a neurophysiological alteration that globally determines DDS. PMID:23185168

  10. Multiple mechanisms of MYCN dysregulation in Wilms tumour

    Science.gov (United States)

    Williams, Richard D.; Chagtai, Tasnim; Alcaide-German, Marisa; Apps, John; Wegert, Jenny; Popov, Sergey; Vujanic, Gordan; van Tinteren, Harm; van den Heuvel-Eibrink, Marry M.; Kool, Marcel; de Kraker, Jan; Gisselsson, David; Graf, Norbert; Gessler, Manfred; Pritchard-Jones, Kathy

    2015-01-01

    Genomic gain of the proto-oncogene transcription factor gene MYCN is associated with poor prognosis in several childhood cancers. Here we present a comprehensive copy number analysis of MYCN in Wilms tumour (WT), demonstrating that gain of this gene is associated with anaplasia and with poorer relapse-free and overall survival, independent of histology. Using whole exome and gene-specific sequencing, together with methylation and expression profiling, we show that MYCN is targeted by other mechanisms, including a recurrent somatic mutation, P44L, and specific DNA hypomethylation events associated with MYCN overexpression in tumours with high risk histologies. We describe parallel evolution of genomic copy number gain and point mutation of MYCN in the contralateral tumours of a remarkable bilateral case in which independent contralateral mutations of TP53 also evolve over time. We report a second bilateral case in which MYCN gain is a germline aberration. Our results suggest a significant role for MYCN dysregulation in the molecular biology of Wilms tumour. We conclude that MYCN gain is prognostically significant, and suggest that the novel P44L somatic variant is likely to be an activating mutation. PMID:25749049

  11. Transcriptional Dysregulation of MYC Reveals Common Enhancer-Docking Mechanism

    Directory of Open Access Journals (Sweden)

    Jurian Schuijers

    2018-04-01

    Full Text Available Summary: Transcriptional dysregulation of the MYC oncogene is among the most frequent events in aggressive tumor cells, and this is generally accomplished by acquisition of a super-enhancer somewhere within the 2.8 Mb TAD where MYC resides. We find that these diverse cancer-specific super-enhancers, differing in size and location, interact with the MYC gene through a common and conserved CTCF binding site located 2 kb upstream of the MYC promoter. Genetic perturbation of this enhancer-docking site in tumor cells reduces CTCF binding, super-enhancer interaction, MYC gene expression, and cell proliferation. CTCF binding is highly sensitive to DNA methylation, and this enhancer-docking site, which is hypomethylated in diverse cancers, can be inactivated through epigenetic editing with dCas9-DNMT. Similar enhancer-docking sites occur at other genes, including genes with prominent roles in multiple cancers, suggesting a mechanism by which tumor cell oncogenes can generally hijack enhancers. These results provide insights into mechanisms that allow a single target gene to be regulated by diverse enhancer elements in different cell types. : Schuijers et al. show that a conserved CTCF site at the promoter of the MYC oncogene plays an important role in enhancer-promoter looping with tumor-specific super-enhancers. Perturbation of this site provides a potential therapeutic vulnerability. Keywords: gene regulation, super-enhancers, chromosome structure, enhancer docking

  12. Gender moderates the relationship between attachment insecurities and emotion dysregulation

    NARCIS (Netherlands)

    Velotti, P.; D’Aguanno, M.; de Campora, G.; di Francescantonio, S.; Garofalo, C.; Giromini, L.; Petrocchi, C.; Terrasi, M.; Zavattini, G.C.

    2016-01-01

    The relation between attachment styles and emotion regulation is well documented, and emotion dysregulation is considered characteristic of individuals with insecure attachment styles. Although gender differences in emotion regulation have often been reported, it is not clear whether the association

  13. Dysregulated behaviors in bulimia nervosa: a case-control study

    OpenAIRE

    Gonçalves, Sónia; Machado, Bárbara Freire Brito César; Martins, C.; Brandão, Isabel; Torres, António Roma; Machado, Paulo P. P.

    2014-01-01

    Background: Bulimia nervosa (BN) is often related to self-control difficulties and to dysregulated behaviours. This study aimed to evaluate the frequency of self-injurious behaviour, suicide attempts, and other dysregulated behaviours in BN, using two control groups (a healthy group and a general psychiatric group), and also to examine the association between these behaviours and alleged sexual abuse in BN.Method: Women (N = 233) aged between 13 and 38 years old were evaluated using a semi-st...

  14. Lamotrigine use in patients with binge eating and purging, significant affect dysregulation, and poor impulse control.

    Science.gov (United States)

    Trunko, Mary Ellen; Schwartz, Terry A; Marzola, Enrica; Klein, Angela S; Kaye, Walter H

    2014-04-01

    Some patients with symptoms of binge eating and purging are successfully treated with specific serotonin reuptake inhibitors (SSRIs), but others experience only partial or no benefit. Significant affect dysregulation and poor impulse control may be characteristics that limit responsiveness. We report on the treatment of five patients with bulimia nervosa (BN), anorexia nervosa-binge/purge type (AN-B/P) or eating disorder not otherwise specified (EDNOS), using the anticonvulsant lamotrigine after inadequate response to SSRIs. Following addition of lamotrigine to an antidepressant in four cases, and switch from an antidepressant to lamotrigine in one case, patients experienced substantial improvement in mood reactivity and instability, impulsive drives and behaviors, and eating-disordered symptoms. These findings raise the possibility that lamotrigine, either as monotherapy or as an augmenting agent to antidepressants, may be useful in patients who binge eat and purge, and have significant affect dysregulation with poor impulse control. Copyright © 2013 Wiley Periodicals, Inc.

  15. Potential Therapeutic Effects of Meditation for Treating Affective Dysregulation

    Directory of Open Access Journals (Sweden)

    Natalie T. Y. Leung

    2014-01-01

    Full Text Available Affective dysregulation is at the root of many psychopathologies, including stress induced disorders, anxiety disorders, and depression. The root of these disorders appears to be an attenuated, top-down cognitive control from the prefrontal cortices over the maladaptive subcortical emotional processing. A form of mental training, long-term meditation practice can trigger meditation-specific neuroplastic changes in the brain regions underlying cognitive control and affective regulation, suggesting that meditation can act as a kind of mental exercise to foster affective regulation and possibly a cost-effective intervention in mood disorders. Increasing research has suggested that the cultivation of awareness and acceptance along with a nonjudgmental attitude via meditation promotes adaptive affective regulation. This review examined the concepts of affective regulation and meditation and discussed behavioral and neural evidence of the potential clinical application of meditation. Lately, there has been a growing trend toward incorporating the “mindfulness” component into existing psychotherapeutic treatment. Promising results have been observed thus far. Future studies may consider exploring the possibility of integrating the element of “compassion” into current psychotherapeutic approaches.

  16. Influenza virus induces apoptosis via BAD-mediated mitochondrial dysregulation.

    Science.gov (United States)

    Tran, Anh T; Cortens, John P; Du, Qiujiang; Wilkins, John A; Coombs, Kevin M

    2013-01-01

    Influenza virus infection results in host cell death and major tissue damage. Specific components of the apoptotic pathway, a signaling cascade that ultimately leads to cell death, are implicated in promoting influenza virus replication. BAD is a cell death regulator that constitutes a critical control point in the intrinsic apoptosis pathway, which occurs through the dysregulation of mitochondrial outer membrane permeabilization and the subsequent activation of downstream apoptogenic factors. Here we report a novel proviral role for the proapoptotic protein BAD in influenza virus replication. We show that influenza virus-induced cytopathology and cell death are considerably inhibited in BAD knockdown cells and that both virus replication and viral protein production are dramatically reduced, which suggests that virus-induced apoptosis is BAD dependent. Our data showed that influenza viruses induced phosphorylation of BAD at residues S112 and S136 in a temporal manner. Viral infection also induced BAD cleavage, late in the viral life cycle, to a truncated form that is reportedly a more potent inducer of apoptosis. We further demonstrate that knockdown of BAD resulted in reduced cytochrome c release and suppression of the intrinsic apoptotic pathway during influenza virus replication, as seen by an inhibition of caspases-3, caspase-7, and procyclic acidic repetitive protein (PARP) cleavage. Our data indicate that influenza viruses carefully modulate the activation of the apoptotic pathway that is dependent on the regulatory function of BAD and that failure of apoptosis activation resulted in unproductive viral replication.

  17. Transcriptional Dysregulation of MYC Reveals Common Enhancer-Docking Mechanism.

    Science.gov (United States)

    Schuijers, Jurian; Manteiga, John Colonnese; Weintraub, Abraham Selby; Day, Daniel Sindt; Zamudio, Alicia Viridiana; Hnisz, Denes; Lee, Tong Ihn; Young, Richard Allen

    2018-04-10

    Transcriptional dysregulation of the MYC oncogene is among the most frequent events in aggressive tumor cells, and this is generally accomplished by acquisition of a super-enhancer somewhere within the 2.8 Mb TAD where MYC resides. We find that these diverse cancer-specific super-enhancers, differing in size and location, interact with the MYC gene through a common and conserved CTCF binding site located 2 kb upstream of the MYC promoter. Genetic perturbation of this enhancer-docking site in tumor cells reduces CTCF binding, super-enhancer interaction, MYC gene expression, and cell proliferation. CTCF binding is highly sensitive to DNA methylation, and this enhancer-docking site, which is hypomethylated in diverse cancers, can be inactivated through epigenetic editing with dCas9-DNMT. Similar enhancer-docking sites occur at other genes, including genes with prominent roles in multiple cancers, suggesting a mechanism by which tumor cell oncogenes can generally hijack enhancers. These results provide insights into mechanisms that allow a single target gene to be regulated by diverse enhancer elements in different cell types. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  18. Emotion dysregulation and social competence: stability, change and predictive power.

    Science.gov (United States)

    Berkovits, L D; Baker, B L

    2014-08-01

    Social difficulties are closely linked to emotion dysregulation among children with typical development (TD). Children with developmental delays (DD) are at risk for poor social outcomes, but the relationship between social and emotional development within this population is not well understood. The current study examines the extent to which emotion dysregulation is related to social problems across middle childhood among children with TD or DD. Children with TD (IQ ≥ 85, n = 113) and children with DD (IQ ≤ 75, n = 61) participated in a longitudinal study. Annual assessments were completed at ages 7, 8 and 9 years. At each assessment, mothers reported on children's emotion dysregulation, and both mothers and teachers reported on children's social difficulties. Children with DD had higher levels of emotion dysregulation and social problems at each age than those with TD. Emotion dysregulation and social problems were significantly positively correlated within both TD and DD groups using mother report of social problems, and within the TD group using teacher report of social problems. Among children with TD, emotion dysregulation consistently predicted change in social problems from one year to the next. However, among children with DD, emotion dysregulation offered no unique prediction value above and beyond current social problems. Results suggested that the influence of emotion regulation abilities on social development may be a less salient pathway for children with DD. These children may have more influences, beyond emotion regulation, on their social behaviour, highlighting the importance of directly targeting social skill deficits among children with DD in order to ameliorate their social difficulties. © 2013 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

  19. An Emerging Role for Long Non-Coding RNA Dysregulation in Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Elio Scarpini

    2013-10-01

    Full Text Available A novel class of transcripts, long non coding RNAs (lncRNAs, has recently emerged as key players in several biological processes, including dosage compensation, genomic imprinting, chromatin regulation, embryonic development and segmentation, stem cell pluripotency, cell fate determination and potentially many other biological processes, which still are to be elucidated. LncRNAs are pervasively transcribed in the genome and several lines of evidence correlate dysregulation of different lncRNAs to human diseases including neurological disorders. Although their mechanisms of action are yet to be fully elucidated, evidence suggests lncRNA contributions to the pathogenesis of a number of diseases. In this review, the current state of knowledge linking lncRNAs to different neurological disorders is discussed and potential future directions are considered.

  20. An Emerging Role for Long Non-Coding RNA Dysregulation in Neurological Disorders

    Science.gov (United States)

    Fenoglio, Chiara; Ridolfi, Elisa; Galimberti, Daniela; Scarpini, Elio

    2013-01-01

    A novel class of transcripts, long non coding RNAs (lncRNAs), has recently emerged as key players in several biological processes, including dosage compensation, genomic imprinting, chromatin regulation, embryonic development and segmentation, stem cell pluripotency, cell fate determination and potentially many other biological processes, which still are to be elucidated. LncRNAs are pervasively transcribed in the genome and several lines of evidence correlate dysregulation of different lncRNAs to human diseases including neurological disorders. Although their mechanisms of action are yet to be fully elucidated, evidence suggests lncRNA contributions to the pathogenesis of a number of diseases. In this review, the current state of knowledge linking lncRNAs to different neurological disorders is discussed and potential future directions are considered. PMID:24129177

  1. GeoSegmenter: A statistically learned Chinese word segmenter for the geoscience domain

    Science.gov (United States)

    Huang, Lan; Du, Youfu; Chen, Gongyang

    2015-03-01

    Unlike English, the Chinese language has no space between words. Segmenting texts into words, known as the Chinese word segmentation (CWS) problem, thus becomes a fundamental issue for processing Chinese documents and the first step in many text mining applications, including information retrieval, machine translation and knowledge acquisition. However, for the geoscience subject domain, the CWS problem remains unsolved. Although a generic segmenter can be applied to process geoscience documents, they lack the domain specific knowledge and consequently their segmentation accuracy drops dramatically. This motivated us to develop a segmenter specifically for the geoscience subject domain: the GeoSegmenter. We first proposed a generic two-step framework for domain specific CWS. Following this framework, we built GeoSegmenter using conditional random fields, a principled statistical framework for sequence learning. Specifically, GeoSegmenter first identifies general terms by using a generic baseline segmenter. Then it recognises geoscience terms by learning and applying a model that can transform the initial segmentation into the goal segmentation. Empirical experimental results on geoscience documents and benchmark datasets showed that GeoSegmenter could effectively recognise both geoscience terms and general terms.

  2. Dysregulated sexuality and high sexual desire: distinct constructs?

    Science.gov (United States)

    Winters, Jason; Christoff, Kalina; Gorzalka, Boris B

    2010-10-01

    The literature on dysregulated sexuality, whether theoretical, clinical or empirical, has failed to differentiate the construct from high sexual desire. In this study, we tested three hypotheses which addressed this issue. A sample of 6458 men and 7938 women, some of whom had sought treatment for sexual compulsivity, addiction or impulsivity, completed an online survey comprised of various sexuality measures. Men and women who reported having sought treatment scored significantly higher on measures of dysregulated sexuality and sexual desire. For men, women, and those who had sought treatment, dysregulated sexuality was associated with increased sexual desire. Confirmatory factor analysis supported a one-factor model, indicating that, in both male and female participants, dysregulated sexuality and sexual desire variables loaded onto a single underlying factor. The results of this study suggest that dysregulated sexuality, as currently conceptualized, labelled, and measured, may simply be a marker of high sexual desire and the distress associated with managing a high degree of sexual thoughts, feelings, and needs.

  3. Dysregulation of Autophagy Contributes to Anal Carcinogenesis.

    Directory of Open Access Journals (Sweden)

    Evie H Carchman

    . With the development of low-grade dysplasia in the K14E6/E7 mice, there was an increase in both punctate LC3β and p62 expression while EM revealed increased autophagosomes without evidence of autophagolysosomes. These observations are consistent with autophagy being inhibited at a later stage in the autophagic process. In contrast, in high-grade dysplasia and SCC in the DMBA-treated K14E6/E7 mice, there were decreased levels of p62 with a continued increase in punctate LC3β expression by IF, while autophagolysosomes were seen on EM, consistent with the process of autophagy proceeded to completion. Similar findings, including histological grade dependent changes in LC3β and p62 expression, were noted with human samples upon analysis of IF. Finally, with pharmacologic inhibition of autophagy in DMBA-treated, nontrangenic FVB/N mice, there was a significant increase in anal cancer development similar to that observed in DMBA- treated K14E6/E7 mice.Autophagic dysregulation is noted early on in HPV-associated anal carcinogenesis (low-grade dysplasia, with normalization of the autophagic process arising in late stages of HPV-associated anal carcinogenesis (high-grade dysplasia and invasive carcinoma.

  4. Metric Learning for Hyperspectral Image Segmentation

    Science.gov (United States)

    Bue, Brian D.; Thompson, David R.; Gilmore, Martha S.; Castano, Rebecca

    2011-01-01

    We present a metric learning approach to improve the performance of unsupervised hyperspectral image segmentation. Unsupervised spatial segmentation can assist both user visualization and automatic recognition of surface features. Analysts can use spatially-continuous segments to decrease noise levels and/or localize feature boundaries. However, existing segmentation methods use tasks-agnostic measures of similarity. Here we learn task-specific similarity measures from training data, improving segment fidelity to classes of interest. Multiclass Linear Discriminate Analysis produces a linear transform that optimally separates a labeled set of training classes. The defines a distance metric that generalized to a new scenes, enabling graph-based segmentation that emphasizes key spectral features. We describe tests based on data from the Compact Reconnaissance Imaging Spectrometer (CRISM) in which learned metrics improve segment homogeneity with respect to mineralogical classes.

  5. Emotion Dysregulation Mediates the Relation between Mindfulness and Rejection Sensitivity.

    Science.gov (United States)

    Velotti, Patrizia; Garofalo, Carlo; Bizzi, Fabiola

    2015-09-01

    The role of rejection sensitivity (RS; the tendency to anxiously expect, readily perceive, and overreact to implied or overt interpersonal rejection) in psychopathology has mainly been studied with regard to borderline personality disorder (BPD). In the present study, we first sought to extend previous evidence of heightened RS in a clinical group with psychiatric disorders other than BPD, when compared with a community sample. Then, we tested whether emotion dysregulation and mindfulness were associated with RS in both sample, further hypothesizing that emotion dysregulation would mediate the relation between mindfulness deficits and RS. We adopted a cross-sectional design involving 191 psychiatric patients and 277 community participants (total N=468). All participants completed the Rejection Sensitivity Questionnaire, the Five Facet Mindfulness Questionnaire, and the Difficulties in Emotion Regulation Scale. Our hypotheses were supported, with psychiatric patients reporting greater levels of rejection sensitivity and emotion dysregulation, and lower level of mindfulness. Mindfulness deficits and emotion dysregulation explained a significant amount of variance in RS, in both samples. Finally, bootstrap analyses revealed that mindfulness deficits played an indirect effect on RS through the mediating role of emotion dysregulation. In particular, two different patterns emerged. Among psychiatric patients, an impairment in the ability to assume a non-judgmental stance towards own thoughts and feelings was related to RS through the mediation of limited access to emotion regulation strategies. Conversely, in the community sample, overall emotion dysregulation mediated the effect of lack of attention and awareness for present activities and experience on RS. Longitudinal studies could help in delineating etiological models of RS, and the joint role of deficits in mindfulness and emotion regulation should inform treatment programs.

  6. Mosaic epigenetic dysregulation of ectodermal cells in autism spectrum disorder.

    Directory of Open Access Journals (Sweden)

    Esther R Berko

    Full Text Available DNA mutational events are increasingly being identified in autism spectrum disorder (ASD, but the potential additional role of dysregulation of the epigenome in the pathogenesis of the condition remains unclear. The epigenome is of interest as a possible mediator of environmental effects during development, encoding a cellular memory reflected by altered function of progeny cells. Advanced maternal age (AMA is associated with an increased risk of having a child with ASD for reasons that are not understood. To explore whether AMA involves covert aneuploidy or epigenetic dysregulation leading to ASD in the offspring, we tested a homogeneous ectodermal cell type from 47 individuals with ASD compared with 48 typically developing (TD controls born to mothers of ≥35 years, using a quantitative genome-wide DNA methylation assay. We show that DNA methylation patterns are dysregulated in ectodermal cells in these individuals, having accounted for confounding effects due to subject age, sex and ancestral haplotype. We did not find mosaic aneuploidy or copy number variability to occur at differentially-methylated regions in these subjects. Of note, the loci with distinctive DNA methylation were found at genes expressed in the brain and encoding protein products significantly enriched for interactions with those produced by known ASD-causing genes, representing a perturbation by epigenomic dysregulation of the same networks compromised by DNA mutational mechanisms. The results indicate the presence of a mosaic subpopulation of epigenetically-dysregulated, ectodermally-derived cells in subjects with ASD. The epigenetic dysregulation observed in these ASD subjects born to older mothers may be associated with aging parental gametes, environmental influences during embryogenesis or could be the consequence of mutations of the chromatin regulatory genes increasingly implicated in ASD. The results indicate that epigenetic dysregulatory mechanisms may complement

  7. Staphylococcal enterotoxins stimulate lymphoma-associated immune dysregulation

    DEFF Research Database (Denmark)

    Krejsgaard, Thorbjørn Frej; Willerslev-Olsen, Andreas; Lindahl, Lise Maria

    2014-01-01

    a cascade of events involving cell-cell and asymmetric cytokine interactions between malignant and benign T cells, which stimulated the malignant T cells to express high levels of IL-10. Much evidence supports that malignant activation of the Stat3/IL-10 axis plays a key role in driving the immune...... dysregulation and severe immunodeficiency that characteristically develops in CTCL patients. The present findings thereby establish a novel link between SEs and immune dysregulation in CTCL strengthening the rationale for antibiotic treatment of colonized patients with severe or progressive disease....

  8. Emotion dysregulation and interpersonal problems : The role of defensiveness

    NARCIS (Netherlands)

    Garofalo, C.; Velotti, Patrizia; Zavattini, Giulio Cesare; Kosson, D.S.

    2017-01-01

    Despite evidence that individual differences in defensiveness (typically measured with social desirability scales) may affect associations among self-report measures, little is known about the impact of defensiveness in the well-established relations between self-report emotion dysregulation and

  9. The Mediating Role of Cognitive Flexibility, Shame and Emotion Dysregulation Between Neuroticism and Depression

    Directory of Open Access Journals (Sweden)

    Majid Zarei

    2018-03-01

    Discussion: These findings suggest that for student depression, emotion dysregulation might be important and future intervention works can examine the effects of targeting emotion dysregulation among university students with high levels of neuroticism and/or depression.

  10. Segmented trapped vortex cavity

    Science.gov (United States)

    Grammel, Jr., Leonard Paul (Inventor); Pennekamp, David Lance (Inventor); Winslow, Jr., Ralph Henry (Inventor)

    2010-01-01

    An annular trapped vortex cavity assembly segment comprising includes a cavity forward wall, a cavity aft wall, and a cavity radially outer wall there between defining a cavity segment therein. A cavity opening extends between the forward and aft walls at a radially inner end of the assembly segment. Radially spaced apart pluralities of air injection first and second holes extend through the forward and aft walls respectively. The segment may include first and second expansion joint features at distal first and second ends respectively of the segment. The segment may include a forward subcomponent including the cavity forward wall attached to an aft subcomponent including the cavity aft wall. The forward and aft subcomponents include forward and aft portions of the cavity radially outer wall respectively. A ring of the segments may be circumferentially disposed about an axis to form an annular segmented vortex cavity assembly.

  11. Pavement management segment consolidation

    Science.gov (United States)

    1998-01-01

    Dividing roads into "homogeneous" segments has been a major problem for all areas of highway engineering. SDDOT uses Deighton Associates Limited software, dTIMS, to analyze life-cycle costs for various rehabilitation strategies on each segment of roa...

  12. Speaker segmentation and clustering

    OpenAIRE

    Kotti, M; Moschou, V; Kotropoulos, C

    2008-01-01

    07.08.13 KB. Ok to add the accepted version to Spiral, Elsevier says ok whlile mandate not enforced. This survey focuses on two challenging speech processing topics, namely: speaker segmentation and speaker clustering. Speaker segmentation aims at finding speaker change points in an audio stream, whereas speaker clustering aims at grouping speech segments based on speaker characteristics. Model-based, metric-based, and hybrid speaker segmentation algorithms are reviewed. Concerning speaker...

  13. Spinal segmental dysgenesis

    Directory of Open Access Journals (Sweden)

    N Mahomed

    2009-06-01

    Full Text Available Spinal segmental dysgenesis is a rare congenital spinal abnormality , seen in neonates and infants in which a segment of the spine and spinal cord fails to develop normally . The condition is segmental with normal vertebrae above and below the malformation. This condition is commonly associated with various abnormalities that affect the heart, genitourinary, gastrointestinal tract and skeletal system. We report two cases of spinal segmental dysgenesis and the associated abnormalities.

  14. Automatic Melody Segmentation

    NARCIS (Netherlands)

    Rodríguez López, Marcelo

    2016-01-01

    The work presented in this dissertation investigates music segmentation. In the field of Musicology, segmentation refers to a score analysis technique, whereby notated pieces or passages of these pieces are divided into “units” referred to as sections, periods, phrases, and so on. Segmentation

  15. Persistent physical symptoms as perceptual dysregulation

    DEFF Research Database (Denmark)

    Henningsen, Peter; Gündel, Harald; Kop, Willem J

    2018-01-01

    OBJECTIVE: The mechanisms underlying the perception and experience of persistent physical symptoms are not well understood, and in the models, the specific relevance of peripheral input versus central processing, or of neurobiological versus psychosocial factors in general, is not clear.In this a......OBJECTIVE: The mechanisms underlying the perception and experience of persistent physical symptoms are not well understood, and in the models, the specific relevance of peripheral input versus central processing, or of neurobiological versus psychosocial factors in general, is not clear.......In this article, we propose a model for this clinical phenomenon that is designed to be coherent with an underlying, relatively new model of the normal brain functions involved in the experience of bodily signals. METHODS: Based on a review of recent literature we describe central elements of this model and its...... of predictions and sensory input. Two possibilities exist: adaptation of the generative model underlying the predictions or alteration of the sensory input via autonomic nervous activation (in the case of interoception). Following this model, persistent physical symptoms can be described as "failures...

  16. Meta-Analysis of Multiple Sclerosis Microarray Data Reveals Dysregulation in RNA Splicing Regulatory Genes

    Directory of Open Access Journals (Sweden)

    Elvezia Maria Paraboschi

    2015-09-01

    Full Text Available Abnormalities in RNA metabolism and alternative splicing (AS are emerging as important players in complex disease phenotypes. In particular, accumulating evidence suggests the existence of pathogenic links between multiple sclerosis (MS and altered AS, including functional studies showing that an imbalance in alternatively-spliced isoforms may contribute to disease etiology. Here, we tested whether the altered expression of AS-related genes represents a MS-specific signature. A comprehensive comparative analysis of gene expression profiles of publicly-available microarray datasets (190 MS cases, 182 controls, followed by gene-ontology enrichment analysis, highlighted a significant enrichment for differentially-expressed genes involved in RNA metabolism/AS. In detail, a total of 17 genes were found to be differentially expressed in MS in multiple datasets, with CELF1 being dysregulated in five out of seven studies. We confirmed CELF1 downregulation in MS (p = 0.0015 by real-time RT-PCRs on RNA extracted from blood cells of 30 cases and 30 controls. As a proof of concept, we experimentally verified the unbalance in alternatively-spliced isoforms in MS of the NFAT5 gene, a putative CELF1 target. In conclusion, for the first time we provide evidence of a consistent dysregulation of splicing-related genes in MS and we discuss its possible implications in modulating specific AS events in MS susceptibility genes.

  17. Dysregulation in level of goal and action identification across psychological disorders

    Science.gov (United States)

    Watkins, Edward

    2011-01-01

    Goals, events, and actions can be mentally represented within a hierarchical framework that ranges from more abstract to more concrete levels of identification. A more abstract level of identification involves general, superordinate, and decontextualized mental representations that convey the meaning of goals, events, and actions, “why” an action is performed, and its purpose, ends, and consequences. A more concrete level of identification involves specific and subordinate mental representations that include contextual details of goals, events, and actions, and the specific “how” details of an action. This review considers three lines of evidence for considering that dysregulation of level of goal/action identification may be a transdiagnostic process. First, there is evidence that different levels of identification have distinct functional consequences and that in non-clinical samples level of goal/action identification appears to be regulated in a flexible and adaptive way to match the level of goal/action identification to circumstances. Second, there is evidence that level of goal/action identification causally influences symptoms and processes involved in psychological disorders, including emotional response, repetitive thought, impulsivity, problem solving and procrastination. Third, there is evidence that the level of goal/action identification is biased and/or dysregulated in certain psychological disorders, with a bias towards more abstract identification for negative events in depression, GAD, PTSD, and social anxiety. PMID:20579789

  18. Pancreatic Islet Protein Complexes and Their Dysregulation in Type 2 Diabetes

    DEFF Research Database (Denmark)

    Pedersen, Helle Krogh; Gudmundsdottir, Valborg; Brunak, Søren

    2017-01-01

    Type 2 diabetes (T2D) is a complex disease that involves multiple genes. Numerous risk loci have already been associated with T2D, although many susceptibility genes remain to be identified given heritability estimates. Systems biology approaches hold potential for discovering novel T2D genes...... by considering their biological context, such as tissue-specific protein interaction partners. Pancreatic islets are a key T2D tissue and many of the known genetic risk variants lead to impaired islet function, hence a better understanding of the islet-specific dysregulation in the disease-state is essential...... to unveil the full potential of person-specific profiles. Here we identify 3,692 overlapping pancreatic islet protein complexes (containing 10,805 genes) by integrating islet gene and protein expression data with protein interactions. We found 24 of these complexes to be significantly enriched for genes...

  19. Pediatric Obesity-Related Asthma: The Role of Metabolic Dysregulation.

    Science.gov (United States)

    Vijayakanthi, Nandini; Greally, John M; Rastogi, Deepa

    2016-05-01

    The burden of obesity-related asthma among children, particularly among ethnic minorities, necessitates an improved understanding of the underlying disease mechanisms. Although obesity is an independent risk factor for asthma, not all obese children develop asthma. Several recent studies have elucidated mechanisms, including the role of diet, sedentary lifestyle, mechanical fat load, and adiposity-mediated inflammation that may underlie the obese asthma pathophysiology. Here, we review these recent studies and emerging scientific evidence that suggest metabolic dysregulation may play a role in pediatric obesity-related asthma. We also review the genetic and epigenetic factors that may underlie susceptibility to metabolic dysregulation and associated pulmonary morbidity among children. Lastly, we identify knowledge gaps that need further exploration to better define pathways that will allow development of primary preventive strategies for obesity-related asthma in children. Copyright © 2016 by the American Academy of Pediatrics.

  20. The primary vascular dysregulation syndrome: implications for eye diseases

    Science.gov (United States)

    2013-01-01

    Vascular dysregulation refers to the regulation of blood flow that is not adapted to the needs of the respective tissue. We distinguish primary vascular dysregulation (PVD, formerly called vasospastic syndrome) and secondary vascular dysregulation (SVD). Subjects with PVD tend to have cold extremities, low blood pressure, reduced feeling of thirst, altered drug sensitivity, increased pain sensitivity, prolonged sleep onset time, altered gene expression in the lymphocytes, signs of oxidative stress, slightly increased endothelin-1 plasma level, low body mass index and often diffuse and fluctuating visual field defects. Coldness, emotional or mechanical stress and starving can provoke symptoms. Virtually all organs, particularly the eye, can be involved. In subjects with PVD, retinal vessels are stiffer and more irregular, and both neurovascular coupling and autoregulation capacity are reduced while retinal venous pressure is often increased. Subjects with PVD have increased risk for normal-tension glaucoma, optic nerve compartment syndrome, central serous choroidopathy, Susac syndrome, retinal artery and vein occlusions and anterior ischaemic neuropathy without atherosclerosis. Further characteristics are their weaker blood–brain and blood-retinal barriers and the higher prevalence of optic disc haemorrhages and activated astrocytes. Subjects with PVD tend to suffer more often from tinnitus, muscle cramps, migraine with aura and silent myocardial ischaemic and are at greater risk for altitude sickness. While the main cause of vascular dysregulation is vascular endotheliopathy, dysfunction of the autonomic nervous system is also involved. In contrast, SVD occurs in the context of other diseases such as multiple sclerosis, retrobulbar neuritis, rheumatoid arthritis, fibromyalgia and giant cell arteritis. Taking into consideration the high prevalence of PVD in the population and potentially linked pathologies, in the current article, the authors provide

  1. Behavioral evidence of emotion dysregulation in binge eaters.

    Science.gov (United States)

    Eichen, Dawn M; Chen, Eunice; Boutelle, Kerri N; McCloskey, Michael S

    2017-04-01

    Binge eating is the most common disordered eating symptom and can lead to the development of obesity. Previous self-report research has supported the hypothesis that individuals who binge eat report greater levels of general emotion dysregulation, which may facilitate binge-eating behavior. However, to date, no study has experimentally tested the relation between binge eating history and in-vivo emotion dysregulation. To do this, a sample of female college students who either endorsed binge eating (n = 40) or denied the presence of any eating pathology (n = 47) completed the Difficulties with Emotion Regulation Scale (DERS) and a behavioral distress tolerance task (the Paced Auditory Serial Addition Task-Computer: PASAT-C) known to induce negative affect and distress. The binge eating group was 2.96 times more likely to quit the PASAT-C early (χ 2  = 5.04, p = 0.025) and reported greater irritability (F(1,84) = 7.09 p = 0.009) and frustration (F(1,84) = 5.00, p = 0.028) after completing the PASAT-C than controls, controlling for initial levels of these emotions. Furthermore, across the entire sample, quitting early was associated with greater emotion dysregulation on the DERS (r pb  = 0.342, p < 0.01). This study is the first to demonstrate that individuals who binge eat show in-vivo emotional dysregulation on a laboratory task. Future studies should examine the PASAT-C to determine its potential clinical utility for individuals with or at risk of developing binge eating. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Microglial Dysregulation in OCD, Tourette Syndrome, and PANDAS

    Directory of Open Access Journals (Sweden)

    Luciana Frick

    2016-01-01

    Full Text Available There is accumulating evidence that immune dysregulation contributes to the pathophysiology of obsessive-compulsive disorder (OCD, Tourette syndrome, and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS. The mechanistic details of this pathophysiology, however, remain unclear. Here we focus on one particular component of the immune system: microglia, the brain’s resident immune cells. The role of microglia in neurodegenerative diseases has been understood in terms of classic, inflammatory activation, which may be both a consequence and a cause of neuronal damage. In OCD and Tourette syndrome, which are not characterized by frank neural degeneration, the potential role of microglial dysregulation is much less clear. Here we review the evidence for a neuroinflammatory etiology and microglial dysregulation in OCD, Tourette syndrome, and PANDAS. We also explore new hypotheses as to the potential contributions of microglial abnormalities to pathophysiology, beyond neuroinflammation, including failures in neuroprotection, lack of support for neuronal survival, and abnormalities in synaptic pruning. Recent advances in neuroimaging and animal model work are creating new opportunities to elucidate these issues.

  3. Microglial Dysregulation in OCD, Tourette Syndrome, and PANDAS

    Science.gov (United States)

    2016-01-01

    There is accumulating evidence that immune dysregulation contributes to the pathophysiology of obsessive-compulsive disorder (OCD), Tourette syndrome, and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). The mechanistic details of this pathophysiology, however, remain unclear. Here we focus on one particular component of the immune system: microglia, the brain's resident immune cells. The role of microglia in neurodegenerative diseases has been understood in terms of classic, inflammatory activation, which may be both a consequence and a cause of neuronal damage. In OCD and Tourette syndrome, which are not characterized by frank neural degeneration, the potential role of microglial dysregulation is much less clear. Here we review the evidence for a neuroinflammatory etiology and microglial dysregulation in OCD, Tourette syndrome, and PANDAS. We also explore new hypotheses as to the potential contributions of microglial abnormalities to pathophysiology, beyond neuroinflammation, including failures in neuroprotection, lack of support for neuronal survival, and abnormalities in synaptic pruning. Recent advances in neuroimaging and animal model work are creating new opportunities to elucidate these issues. PMID:28053994

  4. Dimensions of Emotion Dysregulation in Anorexia Nervosa and Bulimia Nervosa: A Conceptual Review of the Empirical Literature

    Science.gov (United States)

    Lavender, Jason M.; Wonderlich, Stephen A.; Engel, Scott G.; Gordon, Kathryn H.; Kaye, Walter H.; Mitchell, James E.

    2015-01-01

    Several existing conceptual models and psychological interventions address or emphasize the role of emotion dysregulation in eating disorders. The current article uses Gratz and Roemer’s (2004) multidimensional model of emotion regulation and dysregulation as a clinically relevant framework to review the extant literature on emotion dysregulation in anorexia nervosa (AN) and bulimia nervosa (BN). Specifically, the dimensions reviewed include: (1) the flexible use of adaptive and situationally appropriate strategies to modulate the duration and/or intensity of emotional responses, (2) the ability to successfully inhibit impulsive behavior and maintain goal-directed behavior in the context of emotional distress, (3) awareness, clarity, and acceptance of emotional states, and (4) the willingness to experience emotional distress in the pursuit of meaningful activities. The current review suggests that both AN and BN are characterized by broad emotion regulation deficits, with difficulties in emotion regulation across the four dimensions found to characterize both AN and BN, although a small number of more specific difficulties may distinguish the two disorders. The review concludes with a discussion of the clinical implications of the findings, as well as a summary of limitations of the existing empirical literature and suggestions for future research. PMID:26112760

  5. Negative reinforcement eating expectancies, emotion dysregulation, and symptoms of bulimia nervosa.

    Science.gov (United States)

    Hayaki, Jumi

    2009-09-01

    Research suggests that emotion dysregulation or difficulties in the modulation of emotional experience constitute risk for eating disorders. Recent work has also highlighted the role of certain eating-related cognitions, specifically expectations of negative emotional reinforcement from eating, in the development of disturbed eating patterns. However, it is unclear whether these expectancies are merely a dimension of a general inability to regulate emotions effectively or rather a unique cognitive-affective risk factor for the development of an eating disorder. This study examines the unique contribution of eating expectancies to symptoms of bulimia nervosa (BN) after controlling for two dimensions of emotion dysregulation (alexithymia and experiential avoidance) previously implicated in the phenomenology of eating disorders. Participants were 115 undergraduate women who self-reported demographics, alexithymia, experiential avoidance, eating expectancies, and symptoms of BN. Eating expectancies uniquely contributed 12.4% of the variance in symptoms of BN, F(2, 108) = 11.74, p symptoms of BN. These results suggest that individuals who expect eating to provide emotional relief may be especially susceptible to disordered eating. Findings are discussed in terms of emotional risk models and clinical interventions for BN.

  6. Mindfulness and Modification Therapy for Behavioral Dysregulation: A Comparison Trial Focused on Substance Use and Aggression.

    Science.gov (United States)

    Wupperman, Peggilee; Cohen, Mia Gintoft; Haller, Deborah L; Flom, Peter; Litt, Lisa C; Rounsaville, Bruce J

    2015-10-01

    Disorders of behavioral dysregulation often involve more than one dsyregulated behavior (e.g., drug abuse and aggression, alcohol abuse and gambling). The high co-occurrence suggests the need of a transdiagnostic treatment that can be customized to target multiple specific behaviors. The current pilot study compared a 20-week, individual transdiagnostic therapy (mindfulness and modification therapy [MMT]) versus treatment as usual (TAU) in targeting alcohol problems, drug use, physical aggression, and verbal aggression in self-referred women. Assessments were administered at baseline, post-intervention, and 2-month follow-up. Wilcoxon signed-ranked tests and multilevel modeling showed that MMT (n = 13) displayed (a) significant and large decreases in alcohol/drug use, physical aggression, and verbal aggression; (b) significantly greater decreases in alcohol/drug use and physical aggression than did TAU (n = 8); and (c) minimal-to-no deterioration of effects at follow-up. Both conditions showed significant decreases in verbal aggression, with no statistically significant difference between conditions. MMT also displayed greater improvements in mindfulness. Preliminary findings support the feasibility and efficacy of MMT in decreasing multiple dysregulated behaviors. © 2015 Wiley Periodicals, Inc.

  7. No miR quirk: dysregulation of microRNAs in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Cheung, Philip Y; Szafranska-Schwarzbach, Anna E; Schlageter, Annette M; Andruss, Bernard F; Weiss, Glen J

    2012-01-01

    MicroRNAs are post-transcriptional regulators of gene expression with tissue-specific expression profiles. Dysregulation of microRNAs has been shown to play a role in carcinogenesis. Although progress has been made in the diagnosis and treatment of many cancers, pancreatic cancer remains an intractable public health problem, causing 6.58% of cancer deaths despite making up less than 3% of cancer diagnoses in the United States. No screening, diagnostic or imaging techniques exist with the sensitivity to detect pancreatic cancer in its early, operable stages. Risk factors include numerous inherited syndromes, diabetes mellitus, and hepatitis C virus infection. Here we review the literature regarding dysregulation of microRNA expression in native pancreas, pancreatic ductal adenocarcinoma (the dominant form of pancreatic cancer), and its risk factors to illuminate the biology and progression of this disease. We explore promising evidence for the use of microRNAs as prognostic and diagnostic tools, and discuss emerging reports on microRNA therapeutics.

  8. Balancing the fit and logistics costs of market segmentations

    NARCIS (Netherlands)

    Turkensteen, M.; Sierksma, G.; Wieringa, J.E.

    2011-01-01

    Segments are typically formed to serve distinct groups of consumers with differentiated marketing mixes, that better fit their specific needs and wants. However, buyers in a segment are not necessarily geographically closely located. Serving a geographically dispersed segment with one marketing mix

  9. Dysregulated RNA-Induced Silencing Complex (RISC) Assembly within CNS Corresponds with Abnormal miRNA Expression during Autoimmune Demyelination.

    Science.gov (United States)

    Lewkowicz, Przemysław; Cwiklińska, Hanna; Mycko, Marcin P; Cichalewska, Maria; Domowicz, Małgorzata; Lewkowicz, Natalia; Jurewicz, Anna; Selmaj, Krzysztof W

    2015-05-13

    MicroRNAs (miRNAs) associate with Argonaute (Ago), GW182, and FXR1 proteins to form RNA-induced silencing complexes (RISCs). RISCs represent a critical checkpoint in the regulation and bioavailability of miRNAs. Recent studies have revealed dysregulation of miRNAs in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE); however, the function of RISCs in EAE and MS is largely unknown. Here, we examined the expression of Ago, GW182, and FXR1 in CNS tissue, oligodendrocytes (OLs), brain-infiltrating T lymphocytes, and CD3(+)splenocytes (SCs) of EAE mic, and found that global RISC protein levels were significantly dysregulated. Specifically, Ago2 and FXR1 levels were decreased in OLs and brain-infiltrating T cells in EAE mice. Accordingly, assembly of Ago2/GW182/FXR1 complexes in EAE brain tissues was disrupted, as confirmed by immunoprecipitation experiments. In parallel with alterations in RISC complex content in OLs, we found downregulation of miRNAs essential for differentiation and survival of OLs and myelin synthesis. In brain-infiltrating T lymphocytes, aberrant RISC formation contributed to miRNA-dependent proinflammatory helper T-cell polarization. In CD3(+) SCs, we found increased expression of both Ago2 and FXR1 in EAE compared with nonimmunized mice. Therefore, our results demonstrate a gradient in expression of miRNA between primary activated T cells in the periphery and polarized CNS-infiltrating T cells. These results suggest that, in polarized autoreactive effector T cells, miRNA synthesis is inhibited in response to dysregulated RISC assembly, allowing these cells to maintain a highly specific proinflammatory program. Therefore, our findings may provide a mechanism that leads to miRNA dysregulation in EAE/MS. Copyright © 2015 the authors 0270-6474/15/357521-17$15.00/0.

  10. The role of central noradrenergic dysregulation in anxiety disorders: evidence from clinical studies.

    Science.gov (United States)

    Kalk, N J; Nutt, D J; Lingford-Hughes, A R

    2011-01-01

    The nature of the noradrenergic dysregulation in clinical anxiety disorders remains unclear. In panic disorder, the predominant view has been that central noradrenergic neuronal networks and/or the sympathetic nervous system was normal in patients at rest, but hyper-reactive to specific stimuli, for example carbon dioxide. These ideas have been extended to other anxiety disorders, which share with panic disorder characteristic subjective anxiety and physiological symptoms of excess sympathetic activity. For example, Generalized Anxiety Disorder is characterized by chronic free-floating anxiety, muscle tension, palpitation and insomnia. It has been proposed that there is chronic central hypersecretion of noradrenaline in Generalized Anxiety Disorder, with consequent hyporesponsiveness of central post-synaptic receptors. With regards to other disorders, it has been suggested that there is noradrenergic involvement or derangement, but a more specific hypothesis has not been enunciated. This paper reviews the evidence for noradrenergic dysfunction in anxiety disorders, derived from indirect measures of noradrenergic function in clinical populations.

  11. Infant and toddler crying, sleeping and feeding problems and trajectories of dysregulated behavior across childhood.

    Science.gov (United States)

    Winsper, Catherine; Wolke, Dieter

    2014-01-01

    Infant and toddler regulatory problems (RPs) including crying, sleeping and feeding, are a frequent concern for parents and have been associated with negative behavioral outcomes in early and middle childhood. Uncertain is whether infant and toddler RPs predict stable, trait-like dysregulated behavior across childhood. We addressed this gap in the literature using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). RPs at 6, 15-18, & 24-30 months and childhood dysregulated behavior at 4, 7, 8, & 9.5 years were assessed using mother report. Latent Class Growth Analysis (LCGA) indicated that trajectories of childhood dysregulated behavior were stable over time. All single RPs (i.e., crying, sleeping & feeding problems) were significantly associated with childhood dysregulated behavior. For example, crying problems at 6 months after controlling for confounders (Odds Ratios; 95% Confidence Intervals): Moderate dysregulated behavior: OR = 1.50, 95% CI [1.09 to 2.06], high dysregulated behavior: OR = 2.13, 95% CI [1.49 to 3.05] and very high dysregulated behavior: OR = 2.85, 95% CI [1.64 to 4.94]. Multiple RPs were especially strongly associated with dysregulated behavior. For example, the RP composite at 15-18 months: 1 RP, very high dysregulated behavior: OR = 2.79, 95% CI [2.17 to 3.57], 2 RPs, very high dysregulated behavior: OR = 3.46, 95% CI [2.38 to 5.01], 3 RPs, very high dysregulated behavior: OR = 12.57, 95% CI [6.38 to 24.74]. These findings suggest that RPs in infants and toddlers predict stable dysregulated behavior trajectories across childhood. Interventions for early RPs could help prevent the development of chronic, highly dysregulated behavior.

  12. New developments in segment ancillary logic for FASTBUS

    International Nuclear Information System (INIS)

    Walz, H.V.; Bertolucci, B.

    1983-01-01

    Segment Ancillary Logic hardware for FASTBUS systems provides logical functions required in common by all devices attached to a segment. It controls the execution of arbitration cycles, and geographical address cycles, and generates the system handshake responses for broadcast operations. The mandatory requirements for Segment Ancillary Logic in the FASTBUS specifications are reviewed. A detailed implementation based on ECL logic is described, and the hardware to be used on an ECL cable segment for an experimental FASTBUS system at SLAC is shown

  13. Deformable meshes for medical image segmentation accurate automatic segmentation of anatomical structures

    CERN Document Server

    Kainmueller, Dagmar

    2014-01-01

    ? Segmentation of anatomical structures in medical image data is an essential task in clinical practice. Dagmar Kainmueller introduces methods for accurate fully automatic segmentation of anatomical structures in 3D medical image data. The author's core methodological contribution is a novel deformation model that overcomes limitations of state-of-the-art Deformable Surface approaches, hence allowing for accurate segmentation of tip- and ridge-shaped features of anatomical structures. As for practical contributions, she proposes application-specific segmentation pipelines for a range of anatom

  14. Segmentation, advertising and prices

    NARCIS (Netherlands)

    Galeotti, Andrea; Moraga González, José

    This paper explores the implications of market segmentation on firm competitiveness. In contrast to earlier work, here market segmentation is minimal in the sense that it is based on consumer attributes that are completely unrelated to tastes. We show that when the market is comprised by two

  15. Sipunculans and segmentation

    DEFF Research Database (Denmark)

    Wanninger, Andreas; Kristof, Alen; Brinkmann, Nora

    2009-01-01

    mechanisms may act on the level of gene expression, cell proliferation, tissue differentiation and organ system formation in individual segments. Accordingly, in some polychaete annelids the first three pairs of segmental peripheral neurons arise synchronously, while the metameric commissures of the ventral...

  16. Spinal cord grey matter segmentation challenge.

    Science.gov (United States)

    Prados, Ferran; Ashburner, John; Blaiotta, Claudia; Brosch, Tom; Carballido-Gamio, Julio; Cardoso, Manuel Jorge; Conrad, Benjamin N; Datta, Esha; Dávid, Gergely; Leener, Benjamin De; Dupont, Sara M; Freund, Patrick; Wheeler-Kingshott, Claudia A M Gandini; Grussu, Francesco; Henry, Roland; Landman, Bennett A; Ljungberg, Emil; Lyttle, Bailey; Ourselin, Sebastien; Papinutto, Nico; Saporito, Salvatore; Schlaeger, Regina; Smith, Seth A; Summers, Paul; Tam, Roger; Yiannakas, Marios C; Zhu, Alyssa; Cohen-Adad, Julien

    2017-05-15

    An important image processing step in spinal cord magnetic resonance imaging is the ability to reliably and accurately segment grey and white matter for tissue specific analysis. There are several semi- or fully-automated segmentation methods for cervical cord cross-sectional area measurement with an excellent performance close or equal to the manual segmentation. However, grey matter segmentation is still challenging due to small cross-sectional size and shape, and active research is being conducted by several groups around the world in this field. Therefore a grey matter spinal cord segmentation challenge was organised to test different capabilities of various methods using the same multi-centre and multi-vendor dataset acquired with distinct 3D gradient-echo sequences. This challenge aimed to characterize the state-of-the-art in the field as well as identifying new opportunities for future improvements. Six different spinal cord grey matter segmentation methods developed independently by various research groups across the world and their performance were compared to manual segmentation outcomes, the present gold-standard. All algorithms provided good overall results for detecting the grey matter butterfly, albeit with variable performance in certain quality-of-segmentation metrics. The data have been made publicly available and the challenge web site remains open to new submissions. No modifications were introduced to any of the presented methods as a result of this challenge for the purposes of this publication. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways.

    Science.gov (United States)

    Guerenne, Laura; Beurlet, Stéphanie; Said, Mohamed; Gorombei, Petra; Le Pogam, Carole; Guidez, Fabien; de la Grange, Pierre; Omidvar, Nader; Vanneaux, Valérie; Mills, Ken; Mufti, Ghulam J; Sarda-Mantel, Laure; Noguera, Maria Elena; Pla, Marika; Fenaux, Pierre; Padua, Rose Ann; Chomienne, Christine; Krief, Patricia

    2016-01-27

    In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS) patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS) and acute myeloid leukemia (AML) post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

  18. GEP analysis validates high risk MDS and acute myeloid leukemia post MDS mice models and highlights novel dysregulated pathways

    Directory of Open Access Journals (Sweden)

    Laura Guerenne

    2016-01-01

    Full Text Available Abstract Background In spite of the recent discovery of genetic mutations in most myelodysplasic (MDS patients, the pathophysiology of these disorders still remains poorly understood, and only few in vivo models are available to help unravel the disease. Methods We performed global specific gene expression profiling and functional pathway analysis in purified Sca1+ cells of two MDS transgenic mouse models that mimic human high-risk MDS (HR-MDS and acute myeloid leukemia (AML post MDS, with NRASD12 and BCL2 transgenes under the control of different promoters MRP8NRASD12/tethBCL-2 or MRP8[NRASD12/hBCL-2], respectively. Results Analysis of dysregulated genes that were unique to the diseased HR-MDS and AML post MDS mice and not their founder mice pointed first to pathways that had previously been reported in MDS patients, including DNA replication/damage/repair, cell cycle, apoptosis, immune responses, and canonical Wnt pathways, further validating these models at the gene expression level. Interestingly, pathways not previously reported in MDS were discovered. These included dysregulated genes of noncanonical Wnt pathways and energy and lipid metabolisms. These dysregulated genes were not only confirmed in a different independent set of BM and spleen Sca1+ cells from the MDS mice but also in MDS CD34+ BM patient samples. Conclusions These two MDS models may thus provide useful preclinical models to target pathways previously identified in MDS patients and to unravel novel pathways highlighted by this study.

  19. Redox Dysregulation in the Pathophysiology of Schizophrenia and Bipolar Disorder

    DEFF Research Database (Denmark)

    Kulak, Anita; Steullet, Pascal; Cabungcal, Jan-Harry

    2013-01-01

    Abstract Significance: Schizophrenia (SZ) and bipolar disorder (BD) are classified as two distinct diseases. However, accumulating evidence shows that both disorders share genetic, pathological, and epidemiological characteristics. Based on genetic and functional findings, redox dysregulation due...... abnormal prefrontal levels of glutathione (GSH), the major cellular redox regulator and antioxidant. Here we review experimental data from rodent models demonstrating that permanent as well as transient GSH deficit results in behavioral, morphological, electrophysiological, and neurochemical alterations...... hypofunction, elevated glutamate levels, impairment of parvalbumin GABA interneurons, abnormal neuronal synchronization, altered dopamine neurotransmission, and deficient myelination. Critical Issues: Treatment with the GSH precursor and antioxidant N-acetylcysteine normalizes some of those deficits in mice...

  20. The dysregulated cluster in personality profiling research: Longitudinal stability and associations with bulimic behaviors and correlates

    Science.gov (United States)

    Slane, Jennifer D.; Klump, Kelly L.; Donnellan, M. Brent; McGue, Matthew; Iacono, William G.

    2013-01-01

    Among cluster analytic studies of the personality profiles associated with bulimia nervosa, a group of individuals characterized by emotional lability and behavioral dysregulation (i.e., a dysregulated cluster) has emerged most consistently. However, previous studies have all been cross-sectional and mostly used clinical samples. This study aimed to replicate associations between the dysregulated personality cluster and bulimic symptoms and related characteristics using a longitudinal, population-based sample. Participants were females assessed at ages 17 and 25 from the Minnesota Twin Family Study, clustered based on their personality traits. The Dysregulated cluster was successfully identified at both time points and was more stable across time than either the Resilient or Sensation Seeking clusters. Rates of bulimic symptoms and related behaviors (e.g., alcohol use problems) were also highest in the dysregulated group. Findings suggest that the dysregulated cluster is a relatively stable and robust profile that is associated with bulimic symptoms. PMID:23398096

  1. Pancreas and cyst segmentation

    Science.gov (United States)

    Dmitriev, Konstantin; Gutenko, Ievgeniia; Nadeem, Saad; Kaufman, Arie

    2016-03-01

    Accurate segmentation of abdominal organs from medical images is an essential part of surgical planning and computer-aided disease diagnosis. Many existing algorithms are specialized for the segmentation of healthy organs. Cystic pancreas segmentation is especially challenging due to its low contrast boundaries, variability in shape, location and the stage of the pancreatic cancer. We present a semi-automatic segmentation algorithm for pancreata with cysts. In contrast to existing automatic segmentation approaches for healthy pancreas segmentation which are amenable to atlas/statistical shape approaches, a pancreas with cysts can have even higher variability with respect to the shape of the pancreas due to the size and shape of the cyst(s). Hence, fine results are better attained with semi-automatic steerable approaches. We use a novel combination of random walker and region growing approaches to delineate the boundaries of the pancreas and cysts with respective best Dice coefficients of 85.1% and 86.7%, and respective best volumetric overlap errors of 26.0% and 23.5%. Results show that the proposed algorithm for pancreas and pancreatic cyst segmentation is accurate and stable.

  2. Dysregulation of gene expression within the peroxisome proliferator activated receptor pathway in morbidly obese patients.

    Science.gov (United States)

    Hindle, A Katharine; Koury, Jadd; McCaffrey, Tim; Fu, Sidney W; Brody, Fred

    2009-06-01

    The causes of obesity are multifactorial but may include dysregulation of a family of related genes, such as the peroxisome proliferator activated receptor gamma (PPARgamma). When activated, the PPARgamma pathway promotes lipid metabolism. This study used microarray technology to evaluate differential gene expression profiles in obese patients undergoing bariatric surgery. The study enrolled six morbidly obese patients with a body mass index (BMI) exceeding 35 and four nonobese individuals. Blood samples were stabilized in PaxGene tubes (PreAnalytiX), and total RNA was extracted. Next, 100 ng of total RNA was amplified and labeled using the Ovation RNA Amplification System V2 with the Ovation whole-blood reagent (NuGen) before it was hybridized to an Affymetrix (Santa Clara, CA) focus array containing more than 8,500 verified genes. The data were analyzed using an analysis of variance (ANOVA) (p < 0.05) in the GeneSpring program, and potential pathways were identified with the Ingenuity program. Real-time quantitative reverse transcriptase-polymerase chain reaction was used to validate the array data. A total of 97 upregulated genes and 125 downregulated genes were identified. More than a 1.5-fold change was identified between the morbidly obese patients and the control subjects for a cluster of dysregulated genes involving pathways regulating cell metabolism and lipid formation. Specifically, the PPARgamma pathway showed a plethora of dysregulated genes including tumor necrosis factor-alpha (TNFalpha). In morbidly obese patients, TNFalpha expression was increased (upregulated) 1.6-fold. These findings were confirmed using quantitative polymerase chain reaction with a 2.8-fold change. Microarrays are a powerful tool for identifying biomarkers indicating morbid obesity by analyzing differential gene expression profiles. This study confirms the association of PPARgamma with morbid obesity. Also, these findings in blood support previous work documented in tissue

  3. Segmentation of consumer's markets and evaluation of market's segments

    OpenAIRE

    ŠVECOVÁ, Iveta

    2013-01-01

    The goal of this bachelor thesis was to explain a possibly segmentation of consumer´s markets for a chosen company, and to present a suitable goods offer, so it would be suitable to the needs of selected segments. The work is divided into theoretical and practical part. First part describes marketing, segmentation, segmentation of consumer's markets, consumer's market, market's segments a other terms. Second part describes an evaluation of questionnaire survey, discovering of market's segment...

  4. Rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation (ROHHAD syndrome): A case report and literature review.

    Science.gov (United States)

    Ibáñez-Micó, S; Marcos Oltra, A M; de Murcia Lemauviel, S; Ruiz Pruneda, R; Martínez Ferrández, C; Domingo Jiménez, R

    ROHHAD syndrome (rapid-onset obesity with hypothalamic dysregulation, hypoventilation, and autonomic dysregulation) is a rare and complex disease, presenting in previously healthy children at the age of 2-4 years. Up to 40% of cases are associated with neural crest tumours. We present the case of a 2-year-old girl with symptoms of rapidly progressing obesity, who a few months later developed hypothalamic dysfunction with severe electrolyte imbalance, behaviour disorder, hypoventilation, and severe autonomic dysregulation, among other symptoms. Although the pathophysiology of this syndrome remains unclear, an autoimmune hypothesis has been proposed for ROHHAD. Therefore, after obtaining a limited response to intravenous immunoglobulins, we decided to test the response to a high dose cyclophosphamide (low dose was not effective either). Unfortunately our patient experienced many severe complications (among them central pontine myelinolysis, from which the patient recovered, and failure to wean from the ventilator requiring tracheostomy and long term ventilation) that required a prolonged ICU stay. Although her behaviour improved, our patient unfortunately died suddenly at home at the age of 5 due to respiratory pathology. ROHHAD syndrome is a rare and little-known disease which requires a multidisciplinary approach because it involves complex symptoms and multiple organ system involvement. Alveolar hypoventilation should be identified early and appropriate treatment should be started promptly for the best possible outcome. Immunomodulatory treatment with immunoglobulins, cyclophosphamide, or rituximab has previously resulted in symptom improvement in some cases. Because of the low incidence of the syndrome, multi-centre studies must be carried out in order to gather more accurate information about ROHHAD pathophysiology and design an appropriate therapeutic approach. Copyright © 2016 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All

  5. The impact of attachment security and emotion dysregulation on anxiety in children and adolescents

    DEFF Research Database (Denmark)

    Bender, Patrick K.; Sømhovd, Mikael; Pons, Francisco

    2015-01-01

    Theoretical views and empirical findings suggest interrelations among attachment security, emotion dysregulation and anxiety in childhood and adolescence. However, the associations among the three constructs have rarely been investigated in children, and no study has yet addressed...... to anxiety and that emotion dysregulation would help explain the association between attachment security and anxiety. Results showed that more securely attached youths reported less emotion dysregulation and that youths who had fewer emotion regulation difficulties experienced less anxiety. The association...... between attachment security and anxiety was mediated by emotion dysregulation. The model was confirmed for both children and adolescents. Findings are discussed with respect to theoretical implications, as well as future directions....

  6. Functional Dysregulation of CDC42 Causes Diverse Developmental Phenotypes.

    Science.gov (United States)

    Martinelli, Simone; Krumbach, Oliver H F; Pantaleoni, Francesca; Coppola, Simona; Amin, Ehsan; Pannone, Luca; Nouri, Kazem; Farina, Luciapia; Dvorsky, Radovan; Lepri, Francesca; Buchholzer, Marcel; Konopatzki, Raphael; Walsh, Laurence; Payne, Katelyn; Pierpont, Mary Ella; Vergano, Samantha Schrier; Langley, Katherine G; Larsen, Douglas; Farwell, Kelly D; Tang, Sha; Mroske, Cameron; Gallotta, Ivan; Di Schiavi, Elia; Della Monica, Matteo; Lugli, Licia; Rossi, Cesare; Seri, Marco; Cocchi, Guido; Henderson, Lindsay; Baskin, Berivan; Alders, Mariëlle; Mendoza-Londono, Roberto; Dupuis, Lucie; Nickerson, Deborah A; Chong, Jessica X; Meeks, Naomi; Brown, Kathleen; Causey, Tahnee; Cho, Megan T; Demuth, Stephanie; Digilio, Maria Cristina; Gelb, Bruce D; Bamshad, Michael J; Zenker, Martin; Ahmadian, Mohammad Reza; Hennekam, Raoul C; Tartaglia, Marco; Mirzaa, Ghayda M

    2018-01-17

    Exome sequencing has markedly enhanced the discovery of genes implicated in Mendelian disorders, particularly for individuals in whom a known clinical entity could not be assigned. This has led to the recognition that phenotypic heterogeneity resulting from allelic mutations occurs more commonly than previously appreciated. Here, we report that missense variants in CDC42, a gene encoding a small GTPase functioning as an intracellular signaling node, underlie a clinically heterogeneous group of phenotypes characterized by variable growth dysregulation, facial dysmorphism, and neurodevelopmental, immunological, and hematological anomalies, including a phenotype resembling Noonan syndrome, a developmental disorder caused by dysregulated RAS signaling. In silico, in vitro, and in vivo analyses demonstrate that mutations variably perturb CDC42 function by altering the switch between the active and inactive states of the GTPase and/or affecting CDC42 interaction with effectors, and differentially disturb cellular and developmental processes. These findings reveal the remarkably variable impact that dominantly acting CDC42 mutations have on cell function and development, creating challenges in syndrome definition, and exemplify the importance of functional profiling for syndrome recognition and delineation. Copyright © 2017 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  7. Deletion of Fanca or Fancd2 dysregulates Treg in mice

    Science.gov (United States)

    Du, Wei; Erden, Ozlem; Wilson, Andrew; Sipple, Jared M.; Schick, Jonathan; Mehta, Parinda; Myers, Kasiani C.; Steinbrecher, Kris A.; Davies, Stella M.

    2014-01-01

    Fanconi anemia (FA) is a genetic disorder associated with bone marrow (BM) failure and leukemia. Recent studies demonstrate variable immune defects in FA. However, the cause for FA immunodeficiency is unknown. Here we report that deletion of Fanca or Fancd2 dysregulates the suppressive activity of regulatory T cells (Tregs), shown functionally as exacerbation of graft-vs-host disease (GVHD) in mice. Recipient mice of Fanca−/− or Fancd2−/− BM chimeras exhibited severe acute GVHD after allogeneic BM transplantation (BMT). T cells from Fanca−/− or Fancd2−/− mice induced higher GVHD lethality than those from wild-type (WT) littermates. FA Tregs possessed lower proliferative suppression potential compared with WT Tregs, as demonstrated by in vitro proliferation assay and BMT. Analysis of CD25+Foxp3+ Tregs indicated that loss of Fanca or Fancd2 dysregulated Foxp3 target gene expression. Additionally, CD25+Foxp3+ Tregs of Fanca−/− or Fancd2−/− mice were less efficient in suppressing the production of GVHD-associated inflammatory cytokines. Consistently, aberrant NF-κB activity was observed in infiltrated T cells from FA GVHD mice. Conditional deletion of p65 in FA Tregs decreased GVHD mortality. Our study uncovers an essential role for FA proteins in maintaining Treg homeostasis, possibly explaining, at least in part, the immune deficiency reported in some FA patients. PMID:24501220

  8. [Stress and autonomic dysregulation in patients with fibromyalgia syndrome].

    Science.gov (United States)

    Friederich, H-C; Schellberg, D; Mueller, K; Bieber, C; Zipfel, S; Eich, W

    2005-06-01

    The aim of the present study was to evaluate to what extent the orthostatic dysregulation of FMS patients can be attributed primarily to reduced baroreceptor-mediated activation of the sympathetic nervous system and whether a hyporeactive sympathetic nervous system can also be confirmed for mental stress. A total of 28 patients with primary FMS were examined and compared with 15 healthy subjects. Diagnostic investigations of the autonomic nervous system were based on measuring HRV in frequency range and assessing spontaneous baroreflex sensitivity (sBRS) under mental stress and passive orthostatism. Both under orthostatic and mental stress FMS patients exhibited reduced activation of the sympathetic nervous system as measured by the spectral power of HRV in the low-frequency range and the mean arterial blood pressure or heart rate. The present study provided no indications for dysregulation of sBRS. The results obtained confirm the hypothesis of a hyporeactive stress system in FMS patients for both peripherally and centrally mediated stimulation of the sympathetic nervous system.

  9. Transcriptional dysregulation in NIPBL and cohesin mutant human cells.

    Directory of Open Access Journals (Sweden)

    Jinglan Liu

    2009-05-01

    Full Text Available Cohesin regulates sister chromatid cohesion during the mitotic cell cycle with Nipped-B-Like (NIPBL facilitating its loading and unloading. In addition to this canonical role, cohesin has also been demonstrated to play a critical role in regulation of gene expression in nondividing cells. Heterozygous mutations in the cohesin regulator NIPBL or cohesin structural components SMC1A and SMC3 result in the multisystem developmental disorder Cornelia de Lange Syndrome (CdLS. Genome-wide assessment of transcription in 16 mutant cell lines from severely affected CdLS probands has identified a unique profile of dysregulated gene expression that was validated in an additional 101 samples and correlates with phenotypic severity. This profile could serve as a diagnostic and classification tool. Cohesin binding analysis demonstrates a preference for intergenic regions suggesting a cis-regulatory function mimicking that of a boundary/insulator interacting protein. However, the binding sites are enriched within the promoter regions of the dysregulated genes and are significantly decreased in CdLS proband, indicating an alternative role of cohesin as a transcription factor.

  10. Targeting emotion dysregulation in the treatment of self-injury.

    Science.gov (United States)

    Gratz, Kim L

    2007-11-01

    Clinically useful definitions of emotion regulation with respect to deliberate self-harm (referred to here as self-injury) focus on adaptive ways of responding to emotional distress rather than on the control of emotions or dampening of emotional arousal. According to one such definition, emotion regulation is a multifaceted construct involving a) the awareness, understanding, and acceptance of emotions; b) ability to engage in goal-directed behaviors, and inhibit impulsive behaviors, when experiencing negative emotions; c) the flexible use of situationally appropriate strategies to modulate the intensity and/or duration of emotional responses rather than to eliminate emotions entirely; and d) willingness to experience negative emotions as part of pursuing meaningful activities in life (Gratz & Roemer, 2004). This article addresses the role of emotion dysregulation in self-injury and discusses two treatments for self-injury that explicitly focus on increasing emotion regulation. These treatments are based on the premise that the reduction of emotion dysregulation will decrease the need for maladaptive behaviors that function to regulate emotions, such as self-injury. A case illustration describing how one of these treatments (an acceptance-based, emotion regulation group therapy) is used to treat self-injury is provided.

  11. Deletion of Fanca or Fancd2 dysregulates Treg in mice.

    Science.gov (United States)

    Du, Wei; Erden, Ozlem; Wilson, Andrew; Sipple, Jared M; Schick, Jonathan; Mehta, Parinda; Myers, Kasiani C; Steinbrecher, Kris A; Davies, Stella M; Pang, Qishen

    2014-03-20

    Fanconi anemia (FA) is a genetic disorder associated with bone marrow (BM) failure and leukemia. Recent studies demonstrate variable immune defects in FA. However, the cause for FA immunodeficiency is unknown. Here we report that deletion of Fanca or Fancd2 dysregulates the suppressive activity of regulatory T cells (Tregs), shown functionally as exacerbation of graft-vs-host disease (GVHD) in mice. Recipient mice of Fanca(-/-) or Fancd2(-/-) BM chimeras exhibited severe acute GVHD after allogeneic BM transplantation (BMT). T cells from Fanca(-/-) or Fancd2(-/-) mice induced higher GVHD lethality than those from wild-type (WT) littermates. FA Tregs possessed lower proliferative suppression potential compared with WT Tregs, as demonstrated by in vitro proliferation assay and BMT. Analysis of CD25(+)Foxp3(+) Tregs indicated that loss of Fanca or Fancd2 dysregulated Foxp3 target gene expression. Additionally, CD25(+)Foxp3(+) Tregs of Fanca(-/-) or Fancd2(-/-) mice were less efficient in suppressing the production of GVHD-associated inflammatory cytokines. Consistently, aberrant NF-κB activity was observed in infiltrated T cells from FA GVHD mice. Conditional deletion of p65 in FA Tregs decreased GVHD mortality. Our study uncovers an essential role for FA proteins in maintaining Treg homeostasis, possibly explaining, at least in part, the immune deficiency reported in some FA patients.

  12. BCAA Metabolism and Insulin Sensitivity - Dysregulated by Metabolic Status?

    Science.gov (United States)

    Gannon, Nicholas P; Schnuck, Jamie K; Vaughan, Roger A

    2018-03-01

    Branched-chain amino acids (BCAAs) appear to influence several synthetic and catabolic cellular signaling cascades leading to altered phenotypes in mammals. BCAAs are most notably known to increase protein synthesis through modulating protein translation, explaining their appeal to resistance and endurance athletes for muscle hypertrophy, expedited recovery, and preservation of lean body mass. In addition to anabolic effects, BCAAs may increase mitochondrial content in skeletal muscle and adipocytes, possibly enhancing oxidative capacity. However, elevated circulating BCAA levels have been correlated with severity of insulin resistance. It is hypothesized that elevated circulating BCAAs observed in insulin resistance may result from dysregulated BCAA degradation. This review summarizes original reports that investigated the ability of BCAAs to alter glucose uptake in consequential cell types and experimental models. The review also discusses the interplay of BCAAs with other metabolic factors, and the role of excess lipid (and possibly energy excess) in the dysregulation of BCAA catabolism. Lastly, this article provides a working hypothesis of the mechanism(s) by which lipids may contribute to altered BCAA catabolism, which often accompanies metabolic disease. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Autoimmune dysregulation and purine metabolism in adenosine deaminase (ADA-deficiency

    Directory of Open Access Journals (Sweden)

    Aisha Vanessa Sauer

    2012-08-01

    Full Text Available Genetic defects in the adenosine deaminase (ADA gene are among the most common causes for severe combined immunodeficiency (SCID. ADA-SCID patients suffer from lymphopenia, severely impaired cellular and humoral immunity, failure to thrive and recurrent infections. Currently available therapeutic options for this otherwise fatal disorder include bone marrow transplantation (BMT, enzyme replacement therapy with bovine ADA (PEG-ADA or hematopoietic stem cell gene therapy (HSC-GT. Although varying degrees of immune reconstitution can be achieved by these treatments, breakdown of tolerance is a major concern in ADA-SCID. Immune dysregulation such as autoimmune hypothyroidism, diabetes mellitus, hemolytic anemia, and immune thrombocytopenia are frequently observed in milder forms of the disease. However, several reports document similar complications also in patients on long-term PEG-ADA and after BMT or GT treatment.A skewed repertoire and decreased immune functions have been implicated in autoimmunity observed in certain B-cell and/or T-cell immunodeficiencies, but it remains unclear to what extent specific mechanisms of tolerance are affected in ADA deficiency. Herein we provide an overview about ADA-SCID and the autoimmune manifestations reported in these patients before and after treatment. We also assess the value of the ADA-deficient mouse model as a useful tool to study both immune and metabolic disease mechanisms. With focus on regulatory T and B cells we discuss the lymphocyte subpopulations particularly prone to contribute to the loss of self-tolerance and onset of autoimmunity in ADA deficiency. Moreover we address which aspects of immune dysregulation are specifically related to alterations in purine metabolism caused by the lack of ADA and the subsequent accumulation of metabolites with immunomodulatory properties.

  14. Segmental tuberculosis verrucosa cutis

    Directory of Open Access Journals (Sweden)

    Hanumanthappa H

    1994-01-01

    Full Text Available A case of segmental Tuberculosis Verrucosa Cutis is reported in 10 year old boy. The condition was resembling the ascending lymphangitic type of sporotrichosis. The lesions cleared on treatment with INH 150 mg daily for 6 months.

  15. Chromosome condensation and segmentation

    International Nuclear Information System (INIS)

    Viegas-Pequignot, E.M.

    1981-01-01

    Some aspects of chromosome condensation in mammalians -humans especially- were studied by means of cytogenetic techniques of chromosome banding. Two further approaches were adopted: a study of normal condensation as early as prophase, and an analysis of chromosome segmentation induced by physical (temperature and γ-rays) or chemical agents (base analogues, antibiotics, ...) in order to show out the factors liable to affect condensation. Here 'segmentation' means an abnormal chromosome condensation appearing systematically and being reproducible. The study of normal condensation was made possible by the development of a technique based on cell synchronization by thymidine and giving prophasic and prometaphasic cells. Besides, the possibility of inducing R-banding segmentations on these cells by BrdU (5-bromodeoxyuridine) allowed a much finer analysis of karyotypes. Another technique was developed using 5-ACR (5-azacytidine), it allowed to induce a segmentation similar to the one obtained using BrdU and identify heterochromatic areas rich in G-C bases pairs [fr

  16. Fluence map segmentation

    International Nuclear Information System (INIS)

    Rosenwald, J.-C.

    2008-01-01

    The lecture addressed the following topics: 'Interpreting' the fluence map; The sequencer; Reasons for difference between desired and actual fluence map; Principle of 'Step and Shoot' segmentation; Large number of solutions for given fluence map; Optimizing 'step and shoot' segmentation; The interdigitation constraint; Main algorithms; Conclusions on segmentation algorithms (static mode); Optimizing intensity levels and monitor units; Sliding window sequencing; Synchronization to avoid the tongue-and-groove effect; Accounting for physical characteristics of MLC; Importance of corrections for leaf transmission and offset; Accounting for MLC mechanical constraints; The 'complexity' factor; Incorporating the sequencing into optimization algorithm; Data transfer to the treatment machine; Interface between R and V and accelerator; and Conclusions on fluence map segmentation (Segmentation is part of the overall inverse planning procedure; 'Step and Shoot' and 'Dynamic' options are available for most TPS (depending on accelerator model; The segmentation phase tends to come into the optimization loop; The physical characteristics of the MLC have a large influence on final dose distribution; The IMRT plans (MU and relative dose distribution) must be carefully validated). (P.A.)

  17. Gamifying Video Object Segmentation.

    Science.gov (United States)

    Spampinato, Concetto; Palazzo, Simone; Giordano, Daniela

    2017-10-01

    Video object segmentation can be considered as one of the most challenging computer vision problems. Indeed, so far, no existing solution is able to effectively deal with the peculiarities of real-world videos, especially in cases of articulated motion and object occlusions; limitations that appear more evident when we compare the performance of automated methods with the human one. However, manually segmenting objects in videos is largely impractical as it requires a lot of time and concentration. To address this problem, in this paper we propose an interactive video object segmentation method, which exploits, on one hand, the capability of humans to identify correctly objects in visual scenes, and on the other hand, the collective human brainpower to solve challenging and large-scale tasks. In particular, our method relies on a game with a purpose to collect human inputs on object locations, followed by an accurate segmentation phase achieved by optimizing an energy function encoding spatial and temporal constraints between object regions as well as human-provided location priors. Performance analysis carried out on complex video benchmarks, and exploiting data provided by over 60 users, demonstrated that our method shows a better trade-off between annotation times and segmentation accuracy than interactive video annotation and automated video object segmentation approaches.

  18. Strategic market segmentation

    Directory of Open Access Journals (Sweden)

    Maričić Branko R.

    2015-01-01

    Full Text Available Strategic planning of marketing activities is the basis of business success in modern business environment. Customers are not homogenous in their preferences and expectations. Formulating an adequate marketing strategy, focused on realization of company's strategic objectives, requires segmented approach to the market that appreciates differences in expectations and preferences of customers. One of significant activities in strategic planning of marketing activities is market segmentation. Strategic planning imposes a need to plan marketing activities according to strategically important segments on the long term basis. At the same time, there is a need to revise and adapt marketing activities on the short term basis. There are number of criteria based on which market segmentation is performed. The paper will consider effectiveness and efficiency of different market segmentation criteria based on empirical research of customer expectations and preferences. The analysis will include traditional criteria and criteria based on behavioral model. The research implications will be analyzed from the perspective of selection of the most adequate market segmentation criteria in strategic planning of marketing activities.

  19. An unsupervised strategy for biomedical image segmentation

    Directory of Open Access Journals (Sweden)

    Roberto Rodríguez

    2010-09-01

    Full Text Available Roberto Rodríguez1, Rubén Hernández21Digital Signal Processing Group, Institute of Cybernetics, Mathematics, and Physics, Havana, Cuba; 2Interdisciplinary Professional Unit of Engineering and Advanced Technology, IPN, MexicoAbstract: Many segmentation techniques have been published, and some of them have been widely used in different application problems. Most of these segmentation techniques have been motivated by specific application purposes. Unsupervised methods, which do not assume any prior scene knowledge can be learned to help the segmentation process, and are obviously more challenging than the supervised ones. In this paper, we present an unsupervised strategy for biomedical image segmentation using an algorithm based on recursively applying mean shift filtering, where entropy is used as a stopping criterion. This strategy is proven with many real images, and a comparison is carried out with manual segmentation. With the proposed strategy, errors less than 20% for false positives and 0% for false negatives are obtained.Keywords: segmentation, mean shift, unsupervised segmentation, entropy

  20. Deformable segmentation via sparse shape representation.

    Science.gov (United States)

    Zhang, Shaoting; Zhan, Yiqiang; Dewan, Maneesh; Huang, Junzhou; Metaxas, Dimitris N; Zhou, Xiang Sean

    2011-01-01

    Appearance and shape are two key elements exploited in medical image segmentation. However, in some medical image analysis tasks, appearance cues are weak/misleading due to disease/artifacts and often lead to erroneous segmentation. In this paper, a novel deformable model is proposed for robust segmentation in the presence of weak/misleading appearance cues. Owing to the less trustable appearance information, this method focuses on the effective shape modeling with two contributions. First, a shape composition method is designed to incorporate shape prior on-the-fly. Based on two sparsity observations, this method is robust to false appearance information and adaptive to statistically insignificant shape modes. Second, shape priors are modeled and used in a hierarchical fashion. More specifically, by using affinity propagation method, our deformable surface is divided into multiple partitions, on which local shape models are built independently. This scheme facilitates a more compact shape prior modeling and hence a more robust and efficient segmentation. Our deformable model is applied on two very diverse segmentation problems, liver segmentation in PET-CT images and rodent brain segmentation in MR images. Compared to state-of-art methods, our method achieves better performance in both studies.

  1. Segmented block copolymers with monodisperse aramide end-segments

    NARCIS (Netherlands)

    Araichimani, A.; Gaymans, R.J.

    2008-01-01

    Segmented block copolymers were synthesized using monodisperse diaramide (TT) as hard segments and PTMO with a molecular weight of 2 900 g · mol-1 as soft segments. The aramide: PTMO segment ratio was increased from 1:1 to 2:1 thereby changing the structure from a high molecular weight multi-block

  2. Rediscovering market segmentation.

    Science.gov (United States)

    Yankelovich, Daniel; Meer, David

    2006-02-01

    In 1964, Daniel Yankelovich introduced in the pages of HBR the concept of nondemographic segmentation, by which he meant the classification of consumers according to criteria other than age, residence, income, and such. The predictive power of marketing studies based on demographics was no longer strong enough to serve as a basis for marketing strategy, he argued. Buying patterns had become far better guides to consumers' future purchases. In addition, properly constructed nondemographic segmentations could help companies determine which products to develop, which distribution channels to sell them in, how much to charge for them, and how to advertise them. But more than 40 years later, nondemographic segmentation has become just as unenlightening as demographic segmentation had been. Today, the technique is used almost exclusively to fulfill the needs of advertising, which it serves mainly by populating commercials with characters that viewers can identify with. It is true that psychographic types like "High-Tech Harry" and "Joe Six-Pack" may capture some truth about real people's lifestyles, attitudes, self-image, and aspirations. But they are no better than demographics at predicting purchase behavior. Thus they give corporate decision makers very little idea of how to keep customers or capture new ones. Now, Daniel Yankelovich returns to these pages, with consultant David Meer, to argue the case for a broad view of nondemographic segmentation. They describe the elements of a smart segmentation strategy, explaining how segmentations meant to strengthen brand identity differ from those capable of telling a company which markets it should enter and what goods to make. And they introduce their "gravity of decision spectrum", a tool that focuses on the form of consumer behavior that should be of the greatest interest to marketers--the importance that consumers place on a product or product category.

  3. Lifetime Sexual Victimization and Poor Risk Perception: Does Emotion Dysregulation Account for the Links?

    Science.gov (United States)

    Walsh, Kate; DiLillo, David; Messman-Moore, Terri L.

    2012-01-01

    The present study examined whether and which facets of emotion dysregulation serve an intervening role in the association between prior victimization and risk perception in an analogue sexual assault vignette. Participants were 714 university women who completed self-report measures of sexual victimization, emotion dysregulation, and a…

  4. Neurobiology of dysregulated motivational systems in drug addiction

    Science.gov (United States)

    Edwards, Scott; Koob, George F

    2010-01-01

    The progression from recreational drug use to drug addiction impacts multiple neurobiological processes and can be conceptualized as a transition from positive to negative reinforcement mechanisms driving both drug-taking and drug-seeking behaviors. Neurobiological mechanisms for negative reinforcement, defined as drug taking that alleviates a negative emotional state, involve changes in the brain reward system and recruitment of brain stress (or antireward) systems within forebrain structures, including the extended amygdala. These systems are hypothesized to be dysregulated by excessive drug intake and to contribute to allostatic changes in reinforcement mechanisms associated with addiction. Points of intersection between positive and negative motivational circuitry may further drive the compulsivity of drug addiction but also provide a rich neurobiological substrate for therapeutic intervention. PMID:20563312

  5. Understanding periviable birth: A microeconomic alternative to the dysregulation narrative.

    Science.gov (United States)

    Catalano, Ralph; Bruckner, Tim; Avalos, Lyndsay A; Stewart, Holly; Karasek, Deborah; Kariv, Shachar; Gemmill, Alison; Saxton, Katherine; Casey, Joan

    2017-12-12

    Periviable infants (i.e., those born in the 20th through 26th weeks of gestation) suffer much morbidity and approximately half die in the first year of life. Attempts to explain and predict these births disproportionately invoke a "dysregulation" narrative. Research inspired by this narrative has not led to efficacious interventions. The clinical community has, therefore, urged novel approaches to the problem. We aim to provoke debate by offering the theory, inferred from microeconomics, that risk tolerant women carry, without cognitive involvement, high risk fetuses farther into pregnancy than do other women. These extended high-risk pregnancies historically ended in stillbirth but modern obstetric practices now convert a fraction to periviable births. We argue that this theory deserves testing because it suggests inexpensive and noninvasive screening for pregnancies that might benefit from the costly and invasive interventions clinical research will likely devise. Copyright © 2017. Published by Elsevier Ltd.

  6. Dysregulation of chemo-cytokine production in schizophrenic patients versus healthy controls

    Directory of Open Access Journals (Sweden)

    Di Giannantonio Massimo

    2011-01-01

    Full Text Available Abstract Background The exact cause of schizophrenia is not known, although several aetiological theories have been proposed for the disease, including developmental or neurodegenerative processes, neurotransmitter abnormalities, viral infection and immune dysfunction or autoimmune mechanisms. Growing evidence suggests that specific cytokines and chemokines play a role in signalling the brain to produce neurochemical, neuroendocrine, neuroimmune and behavioural changes. A relationship between inflammation and schizophrenia was supported by abnormal cytokines production, abnormal concentrations of cytokines and cytokine receptors in the blood and cerebrospinal fluid in schizophrenia. Since the neuropathology of schizophrenia has recently been reported to be closely associated with microglial activation we aimed to determined whether spontaneous or LPS-induced peripheral blood mononuclear cell chemokines and cytokines production is dysregulated in schizophrenic patients compared to healthy subjects. We enrolled 51 untreated first-episode schizophrenics (SC and 40 healthy subjects (HC and the levels of MCP-1, MIP-1α, IL-8, IL-18, IFN-γ and RANTES were determined by Elisa method in cell-free supernatants of PBMC cultures. Results In the simultaneous quantification we found significantly higher levels of constitutively and LPS-induced MCP-1, MIP-1α, IL-8 and IL-18, and lower RANTES and IFNγ levels released by PBMC of SC patients compared with HC. In ten SC patients receiving therapy with risperidone, olanzapine or clozapine basal and LPS-induced production of RANTES and IL-18 was increased, while both basal and LPS-induced MCP-1 production was decreased. No statistically significant differences were detected in serum levels after therapy. Conclusion The observation that in schizophrenic patients the PBMC production of selected chemo-cytokines is dysregulated reinforces the hypothesis that the peripheral cyto-chemokine network is involved in the

  7. Getting too sweet: galectin-1 dysregulation in gestational diabetes mellitus.

    Science.gov (United States)

    Blois, Sandra M; Gueuvoghlanian-Silva, Barbara Y; Tirado-González, Irene; Torloni, Maria R; Freitag, Nancy; Mattar, Rosiane; Conrad, Melanie L; Unverdorben, Laura; Barrientos, Gabriela; Knabl, Julia; Toldi, Gergely; Molvarec, Attila; Rose, Matthias; Markert, Udo R; Jeschke, Udo; Daher, Silvia

    2014-07-01

    Galectin-1 (gal-1) is a prototype carbohydrate-binding protein, whose dysregulation is associated with adverse pregnancy outcomes such as spontaneous abortion and pre-eclampsia. Furthermore, it is known that faulty gal-1 protein production or gene regulation can be caused by single-nucleotide polymorphisms in the LGALS1 gene. Gestational diabetes mellitus (GDM) is also an adverse pregnancy outcome and the most common metabolic disorder during gestation. However, gal-1 expression patterns during GDM remain largely unknown. Our aims were to define local and peripheral gal-1 expression patterns during pregnancy, and to investigate LGALS1 gene polymorphisms in GDM patients. Circulating gal-1 levels were determined by ELISA in GDM patients and normal pregnant controls, and LGALS1 gene polymorphisms were assessed for association with GDM. Placental tissues were collected from control and GDM term pregnancies to evaluate local gal-1 expression by immunofluorescence. Our results show that GDM is associated with a failure to increase circulating gal-1 levels during the second and third trimester, as well as overexpression of gal-1 in placental tissue. Additionally, the LGALS1 polymorphism rs4820294 was associated with the development of GDM. In pregnancies complicated by GDM, we observed gal-1 dysregulation both locally in the placenta and peripherally in the circulation. Furthermore, the association between the LGALS1 polymorphism and GDM may indicate a genetic contribution to this adverse pregnancy outcome. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Scorpion image segmentation system

    Science.gov (United States)

    Joseph, E.; Aibinu, A. M.; Sadiq, B. A.; Bello Salau, H.; Salami, M. J. E.

    2013-12-01

    Death as a result of scorpion sting has been a major public health problem in developing countries. Despite the high rate of death as a result of scorpion sting, little report exists in literature of intelligent device and system for automatic detection of scorpion. This paper proposed a digital image processing approach based on the floresencing characteristics of Scorpion under Ultra-violet (UV) light for automatic detection and identification of scorpion. The acquired UV-based images undergo pre-processing to equalize uneven illumination and colour space channel separation. The extracted channels are then segmented into two non-overlapping classes. It has been observed that simple thresholding of the green channel of the acquired RGB UV-based image is sufficient for segmenting Scorpion from other background components in the acquired image. Two approaches to image segmentation have also been proposed in this work, namely, the simple average segmentation technique and K-means image segmentation. The proposed algorithm has been tested on over 40 UV scorpion images obtained from different part of the world and results obtained show an average accuracy of 97.7% in correctly classifying the pixel into two non-overlapping clusters. The proposed 1system will eliminate the problem associated with some of the existing manual approaches presently in use for scorpion detection.

  9. Segmentation of complex document

    Directory of Open Access Journals (Sweden)

    Souad Oudjemia

    2014-06-01

    Full Text Available In this paper we present a method for segmentation of documents image with complex structure. This technique based on GLCM (Grey Level Co-occurrence Matrix used to segment this type of document in three regions namely, 'graphics', 'background' and 'text'. Very briefly, this method is to divide the document image, in block size chosen after a series of tests and then applying the co-occurrence matrix to each block in order to extract five textural parameters which are energy, entropy, the sum entropy, difference entropy and standard deviation. These parameters are then used to classify the image into three regions using the k-means algorithm; the last step of segmentation is obtained by grouping connected pixels. Two performance measurements are performed for both graphics and text zones; we have obtained a classification rate of 98.3% and a Misclassification rate of 1.79%.

  10. Dissecting microRNA dysregulation in age-related macular degeneration: new targets for eye gene therapy.

    Science.gov (United States)

    Askou, Anne Louise; Alsing, Sidsel; Holmgaard, Andreas; Bek, Toke; Corydon, Thomas J

    2018-02-01

    MicroRNAs (miRNAs) are key regulators of gene expression in humans. Overexpression or depletion of individual miRNAs is associated with human disease. Current knowledge suggests that the retina is influenced by miRNAs and that dysregulation of miRNAs as well as alterations in components of the miRNA biogenesis machinery are involved in retinal diseases, including age-related macular degeneration (AMD). Furthermore, recent studies have indicated that the vitreous has a specific panel of circulating miRNAs and that this panel varies according to the specific pathological stress experienced by the retinal cells. MicroRNA (miRNA) profiling indicates subtype-specific miRNA profiles for late-stage AMD highlighting the importance of proper miRNA regulation in AMD. This review will describe the function of important miRNAs involved in inflammation, oxidative stress and pathological neovascularization, the key molecular mechanisms leading to AMD, and focus on dysregulated miRNAs as potential therapeutic targets in AMD. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  11. Process Segmentation Typology in Czech Companies

    Directory of Open Access Journals (Sweden)

    Tucek David

    2016-03-01

    Full Text Available This article describes process segmentation typology during business process management implementation in Czech companies. Process typology is important for a manager’s overview of process orientation as well as for a manager’s general understanding of business process management. This article provides insight into a process-oriented organizational structure. The first part analyzes process segmentation typology itself as well as some original results of quantitative research evaluating process segmentation typology in the specific context of Czech company strategies. Widespread data collection was carried out in 2006 and 2013. The analysis of this data showed that managers have more options regarding process segmentation and its selection. In terms of practicality and ease of use, the most frequently used method of process segmentation (managerial, main, and supportive stems directly from the requirements of ISO 9001. Because of ISO 9001:2015, managers must now apply risk planning in relation to the selection of processes that are subjected to process management activities. It is for this fundamental reason that this article focuses on process segmentation typology.

  12. Segmentation in cinema perception.

    Science.gov (United States)

    Carroll, J M; Bever, T G

    1976-03-12

    Viewers perceptually segment moving picture sequences into their cinematically defined units: excerpts that follow short film sequences are recognized faster when the excerpt originally came after a structural cinematic break (a cut or change in the action) than when it originally came before the break.

  13. Dictionary Based Image Segmentation

    DEFF Research Database (Denmark)

    Dahl, Anders Bjorholm; Dahl, Vedrana Andersen

    2015-01-01

    We propose a method for weakly supervised segmentation of natural images, which may contain both textured or non-textured regions. Our texture representation is based on a dictionary of image patches. To divide an image into separated regions with similar texture we use an implicit level sets...

  14. Unsupervised Image Segmentation

    Czech Academy of Sciences Publication Activity Database

    Haindl, Michal; Mikeš, Stanislav

    2014-01-01

    Roč. 36, č. 4 (2014), s. 23-23 R&D Projects: GA ČR(CZ) GA14-10911S Institutional support: RVO:67985556 Keywords : unsupervised image segmentation Subject RIV: BD - Theory of Information http://library.utia.cas.cz/separaty/2014/RO/haindl-0434412.pdf

  15. Metrics for image segmentation

    Science.gov (United States)

    Rees, Gareth; Greenway, Phil; Morray, Denise

    1998-07-01

    An important challenge in mapping image-processing techniques onto applications is the lack of quantitative performance measures. From a systems engineering perspective these are essential if system level requirements are to be decomposed into sub-system requirements which can be understood in terms of algorithm selection and performance optimization. Nowhere in computer vision is this more evident than in the area of image segmentation. This is a vigorous and innovative research activity, but even after nearly two decades of progress, it remains almost impossible to answer the question 'what would the performance of this segmentation algorithm be under these new conditions?' To begin to address this shortcoming, we have devised a well-principled metric for assessing the relative performance of two segmentation algorithms. This allows meaningful objective comparisons to be made between their outputs. It also estimates the absolute performance of an algorithm given ground truth. Our approach is an information theoretic one. In this paper, we describe the theory and motivation of our method, and present practical results obtained from a range of state of the art segmentation methods. We demonstrate that it is possible to measure the objective performance of these algorithms, and to use the information so gained to provide clues about how their performance might be improved.

  16. COMPARISON OF DIFFERENT SEGMENTATION ALGORITHMS FOR DERMOSCOPIC IMAGES

    Directory of Open Access Journals (Sweden)

    A.A. Haseena Thasneem

    2015-05-01

    Full Text Available This paper compares different algorithms for the segmentation of skin lesions in dermoscopic images. The basic segmentation algorithms compared are Thresholding techniques (Global and Adaptive, Region based techniques (K-means, Fuzzy C means, Expectation Maximization and Statistical Region Merging, Contour models (Active Contour Model and Chan - Vese Model and Spectral Clustering. Accuracy, sensitivity, specificity, Border error, Hammoude distance, Hausdorff distance, MSE, PSNR and elapsed time metrices were used to evaluate various segmentation techniques.

  17. Transcriptional dysregulation causes altered modulation of inhibition by haloperidol.

    Science.gov (United States)

    Brady, Lillian J; Bartley, Aundrea F; Li, Qin; McMeekin, Laura J; Hablitz, John J; Cowell, Rita M; Dobrunz, Lynn E

    2016-12-01

    Many neuropsychiatric and neurodevelopmental disorders such as schizophrenia and autism involve interneuron transcriptional dysregulation. The transcriptional coactivator PGC-1α regulates gene expression in GABAergic interneurons, which are important for regulating hippocampal network activity. Genetic deletion of PGC-1α causes a decrease in parvalbumin expression, similar to what is observed in schizophrenia postmortem tissue. Our lab has previously shown that PGC-1α -/- mice have enhanced GABAergic inhibition onto CA1 pyramidal cells, which increases the inhibition/excitation (I/E) ratio, alters hippocampal circuit function, and impairs hippocampal dependent behavior. The typical antipsychotic haloperidol, a dopamine receptor antagonist with selectivity for D2-like receptors, has previously been shown to increase excitation in the CA1 region of hippocampus. We therefore tested whether haloperidol could normalize the I/E balance in CA1 of PGC-1α -/- mice, potentially improving circuit function and behavior. Surprisingly, we discovered instead that interneuron transcriptional dysregulation caused by loss of PGC-1α alters the effects of haloperidol on hippocampal synaptic transmission and circuit function. Acute administration of haloperidol causes disinhibition in CA1 and decreases the I/E ratio onto CA1 pyramidal cells in slices from PGC-1α +/+ mice, but not PGC-1α -/- mice. The spread of activity in CA1, assessed by voltage sensitive dye imaging, is increased by haloperidol in slices from PGC-1α +/+ mice; however haloperidol decreases the spread of activity in slices from PGC-1α -/- mice. Haloperidol increased the power of hippocampal gamma oscillation in slices from PGC-1α +/+ mice but reduced the power of gamma oscillations in slices from PGC-1α -/- mice. Nest construction, an innate hippocampal-dependent behavior, is inhibited by haloperidol in PGC-1α +/+ mice, but not in PGC-1α -/- mice, which already have impaired nest building. The effects of

  18. Structural determinants of alpha-bungarotoxin binding to the sequence segment 181-200 of the muscle nicotinic acetylcholine receptor α subunit: Effects of cysteine/cystine modification and species-specific amino acid substitution

    International Nuclear Information System (INIS)

    McLane, K.E.; Wu, Xiadong; Diethelm, B.; Conti-Tronconi, B.M.

    1991-01-01

    The sequence segment 181-200 of the Torpedo nicotinic acetylcholine receptor (nAChR) αsubunit forms a binding site for α-bungarotoxin (α-BTX). Synthetic peptides corresponding to the homologous sequences of human, calf, mouse, chicken, frog, and cobra muscle nAChR α1 subunits were tested for their ability to bind 125 I-α-BTX, and differences in α-BTX affinity were determined by using solution (IC 50 s) and solid-phase (K d s) assays. Panels of overlapping peptides corresponding to the complete α1 subunit of mouse and human were also tested for α-BTX binding, but other sequence segments forming the α-BTX site were not consistently detectable. The role of a putative vicinal disulfide bound between Cys-192 and -193, relative to the Torpedo sequence, was determined by modifying the peptides with sulfhydryl reagents. Reduction and alkylation of the peptides decreased α-BTX binding, whereas oxidation of the peptides had little effect. These results indicate that while the adjacent cysteines are likely to be involved in forming the toxin/α1-subunit interface a vicinal disulfide bound was not required for α-BTX binding

  19. FAS/FASL are dysregulated in chordoma and their loss-of-function impairs zebrafish notochord formation.

    Science.gov (United States)

    Ferrari, Luca; Pistocchi, Anna; Libera, Laura; Boari, Nicola; Mortini, Pietro; Bellipanni, Gianfranco; Giordano, Antonio; Cotelli, Franco; Riva, Paola

    2014-07-30

    Chordoma is a rare malignant tumor that recapitulates the notochord phenotype and is thought to derive from notochord remnants not correctly regressed during development. Apoptosis is necessary for the proper notochord development in vertebrates, and the apoptotic pathway mediated by Fas and Fasl has been demonstrated to be involved in notochord cells regression. This study was conducted to investigate the expression of FAS/FASL pathway in a cohort of skull base chordomas and to analyze the role of fas/fasl homologs in zebrafish notochord formation. FAS/FASL expression was found to be dysregulated in chordoma leading to inactivation of the downstream Caspases in the samples analyzed. Both fas and fasl were specifically expressed in zebrafish notochord sorted cells. fas and fasl loss-of-function mainly resulted in larvae with notochord multi-cell-layer jumps organization, larger vacuolated notochord cells, defects in the peri-notochordal sheath structure and in vertebral mineralization. Interestingly, we observed the persistent expression of ntla and col2a1a, the zebrafish homologs of the human T gene and COL2A1 respectively, which are specifically up-regulated in chordoma. These results demonstrate for the first time the dysregulation of FAS/FASL in chordoma and their role in notochord formation in the zebrafish model, suggesting their possible implication in chordoma onset.

  20. Pediatric emotional dysregulation and behavioral disruptiveness treated with hypnosis: a time-series design.

    Science.gov (United States)

    Iglesias, Alex; Iglesias, Adam

    2014-01-01

    A case of pediatric oppositional defiant disorder (ODD) with concomitant emotional dysregulation and secondary behavioral disruptiveness was treated with hypnosis by means of the hypnotic hold, a method adapted by the authors. An A-B-A-B time-series design with multiple replications was employed to measure the relationship of the hypnotic treatment to the dependent measure: episodes of emotional dysregulation with accompanying behavioral disruptiveness. The findings indicated a statistically significant relationship between the degree of change from phase to phase and the treatment. Follow-up at 6 months indicated a significant reduction of the frequency of targeted episodes of emotional dysregulation and behavioral disruptiveness at home.

  1. Language-universal constraints on speech segmentation

    NARCIS (Netherlands)

    Norris, D.; McQueen, J.M.; Cutler, A.; Butterfield, S.; Kearns, R.K.

    2001-01-01

    Two word-spotting experiments are reported that examine whether the Possible-Word Constraint (PWC; Norris, McQueen, Cutler & Butterfield, 1997) is a language-specific or language-universal strategy for the segmentation of continuous speech. The PWC disfavors parses which leave an impossible residue

  2. Dysregulated Functions of Lung Macrophage Populations in COPD.

    Science.gov (United States)

    Kapellos, Theodore S; Bassler, Kevin; Aschenbrenner, Anna C; Fujii, Wataru; Schultze, Joachim L

    2018-01-01

    Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema. Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses. To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire. In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations. We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD. In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD.

  3. Dysregulation of Histone Acetyltransferases and Deacetylases in Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Yonggang Wang

    2014-01-01

    Full Text Available Cardiovascular disease (CVD remains a leading cause of mortality worldwide despite advances in its prevention and management. A comprehensive understanding of factors which contribute to CVD is required in order to develop more effective treatment options. Dysregulation of epigenetic posttranscriptional modifications of histones in chromatin is thought to be associated with the pathology of many disease models, including CVD. Histone acetyltransferases (HATs and deacetylases (HDACs are regulators of histone lysine acetylation. Recent studies have implicated a fundamental role of reversible protein acetylation in the regulation of CVDs such as hypertension, pulmonary hypertension, diabetic cardiomyopathy, coronary artery disease, arrhythmia, and heart failure. This reversible acetylation is governed by enzymes that HATs add or HDACs remove acetyl groups respectively. New evidence has revealed that histone acetylation regulators blunt cardiovascular and related disease states in certain cellular processes including myocyte hypertrophy, apoptosis, fibrosis, oxidative stress, and inflammation. The accumulating evidence of the detrimental role of histone acetylation in cardiac disease combined with the cardioprotective role of histone acetylation regulators suggests that the use of histone acetylation regulators may serve as a novel approach to treating the millions of patients afflicted by cardiac diseases worldwide.

  4. Iron dysregulation combined with aging prevents sepsis-induced apoptosis.

    Science.gov (United States)

    Javadi, Pardis; Buchman, Timothy G; Stromberg, Paul E; Turnbull, Isaiah R; Vyas, Dinesh; Hotchkiss, Richard S; Karl, Irene E; Coopersmith, Craig M

    2005-09-01

    Sepsis, iron loading, and aging cause independent increases in gut epithelial and splenic apoptosis. It is unknown how their combination will affect apoptosis and systemic cytokine levels. Hfe-/- mice (a murine homologue of hemochromatosis) abnormally accumulate iron in their tissues. Aged (24-26 months) or mature (16-18 months) Hfe-/- mice and wild type (WT) littermates were subjected to cecal ligation and puncture (CLP) or sham laparotomy. Intestine, spleen, and blood were harvested 24 h later and assessed for apoptosis and cytokine levels. Gut epithelial and splenic apoptosis were low in both aged septic and sham Hfe-/- mice, regardless of the amount of iron in their diet. Mature septic WT mice had increased apoptosis compared to age-matched sham WT mice. Mature septic Hfe-/- mice had similar levels of intestinal cell death to age-matched septic WT mice but higher levels of splenic apoptosis. Apoptosis was significantly lower in septic aged Hfe-/- mice than septic mature Hfe-/- animals. Interleukin-6 was elevated in septic aged Hfe-/- mice compared to sham mice. Although sepsis, chronic iron dysregulation, and aging each increase gut and splenic apoptosis, their combination yields cell death levels similar to sham animals despite the fact that aged Hfe-/- mice are able to mount an inflammatory response following CLP and mature Hfe-/- mice have elevated sepsis-induced apoptosis. Combining sepsis with two risk factors that ordinarily increase cell death and increase mortality in CLP yields an apoptotic response that could not have been predicted based upon each element in isolation.

  5. Dysregulation of Nutrient Sensing and CLEARance in Presenilin Deficiency

    Directory of Open Access Journals (Sweden)

    Kavya Reddy

    2016-03-01

    Full Text Available Attenuated auto-lysosomal system has been associated with Alzheimer disease (AD, yet all underlying molecular mechanisms leading to this impairment are unknown. We show that the amino acid sensing of mechanistic target of rapamycin complex 1 (mTORC1 is dysregulated in cells deficient in presenilin, a protein associated with AD. In these cells, mTORC1 is constitutively tethered to lysosomal membranes, unresponsive to starvation, and inhibitory to TFEB-mediated clearance due to a reduction in Sestrin2 expression. Normalization of Sestrin2 levels through overexpression or elevation of nuclear calcium rescued mTORC1 tethering and initiated clearance. While CLEAR network attenuation in vivo results in buildup of amyloid, phospho-Tau, and neurodegeneration, presenilin-knockout fibroblasts and iPSC-derived AD human neurons fail to effectively initiate autophagy. These results propose an altered mechanism for nutrient sensing in presenilin deficiency and underline an importance of clearance pathways in the onset of AD.

  6. Dysregulation of striatal projection neurons in Parkinson's disease.

    Science.gov (United States)

    Beck, Goichi; Singh, Arun; Papa, Stella M

    2018-03-01

    The loss of nigrostriatal dopamine (DA) is the primary cause of motor dysfunction in Parkinson's disease (PD), but the underlying striatal mechanisms remain unclear. In spite of abundant literature portraying structural, biochemical and plasticity changes of striatal projection neurons (SPNs), in the past there has been a data vacuum from the natural human disease and its close model in non-human primates. Recently, single-cell recordings in advanced parkinsonian primates have generated new insights into the altered function of SPNs. Currently, there are also human data that provide direct evidence of profoundly dysregulated SPN activity in PD. Here, we review primate recordings that are impacting our understanding of the striatal dysfunction after DA loss, particularly through the analysis of physiologic correlates of parkinsonian motor behaviors. In contrast to recordings in rodents, data obtained in primates and patients demonstrate similar major abnormalities of the spontaneous SPN firing in the alert parkinsonian state. Furthermore, these studies also show altered SPN responses to DA replacement in the advanced parkinsonian state. Clearly, there is yet much to learn about the striatal discharges in PD, but studies using primate models are contributing unique information to advance our understanding of pathophysiologic mechanisms.

  7. Lysosome and calcium dysregulation in Alzheimer's disease: partners in crime.

    Science.gov (United States)

    McBrayer, MaryKate; Nixon, Ralph A

    2013-12-01

    Early-onset FAD (familial Alzheimer's disease) is caused by mutations of PS1 (presenilin 1), PS2 (presenilin 2) and APP (amyloid precursor protein). Beyond the effects of PS1 mutations on proteolytic functions of the γ-secretase complex, mutant or deficient PS1 disrupts lysosomal function and Ca2+ homoeostasis, both of which are considered strong pathogenic factors in FAD. Loss of PS1 function compromises assembly and proton-pumping activity of the vacuolar-ATPase on lysosomes, leading to defective lysosomal acidification and marked impairment of autophagy. Additional dysregulation of cellular Ca2+ by mutant PS1 in FAD has been ascribed to altered ion channels in the endoplasmic reticulum; however, rich stores of Ca2+ in lysosomes are also abnormally released in PS1-deficient cells secondary to the lysosomal acidification defect. The resultant rise in cytosolic Ca2+ activates Ca2+-dependent enzymes, contributing substantially to calpain overactivation that is a final common pathway leading to neurofibrillary degeneration in all forms of AD (Alzheimer's disease). In the present review, we discuss the close inter-relationships among deficits of lysosomal function, autophagy and Ca2+ homoeostasis as a pathogenic process in PS1-related FAD and their relevance to sporadic AD.

  8. [Pain and emotional dysregulation: Cellular memory due to pain].

    Science.gov (United States)

    Narita, Minoru; Watanabe, Moe; Hamada, Yusuke; Tamura, Hideki; Ikegami, Daigo; Kuzumaki, Naoko; Igarashi, Katsuhide

    2015-08-01

    Genetic factors are involved in determinants for the risk of psychiatric disorders, and neurological and neurodegenerative diseases. Chronic pain stimuli and intense pain have effects at a cellular and/or gene expression level, and will eventually induce "cellular memory due to pain", which means that tissue damage, even if only transient, can elicit epigenetically abnormal transcription/translation and post-translational modification in related cells depending on the degree or kind of injury or associated conditions. Such cell memory/transformation due to pain can cause an abnormality in a fundamental intracellular response, such as a change in the three-dimensional structure of DNA, transcription, or translation. On the other hand, pain is a multidimensional experience with sensory-discriminative and motivational-affective components. Recent human brain imaging studies have examined differences in activity in the nucleus accumbens between controls and patients with chronic pain, and have revealed that the nucleus accumbens plays a role in predicting the value of a noxious stimulus and its offset, and in the consequent changes in the motivational state. In this review, we provide a very brief overview of a comprehensive understanding of chronic pain associated with emotional dysregulation due to transcriptional regulation, epigenetic modification and miRNA regulation.

  9. Dopamine dysregulation syndrome in Parkinson’s disease

    Directory of Open Access Journals (Sweden)

    A V Nikitina

    2013-01-01

    Full Text Available Dopamine dysregulation syndrome (DDS is an iatrogenic disease developing during dopaminergic therapy. According to the data available in the literature, DDS develops in 3-4% of the Parkinson’s disease (PD cases. DDS in PD is frequently accompanied by other impulse control disorders (ICD: punding, compulsive shopping, hypersexuality, overeating. 246 patients with PD, of whom 16 (6.4% were found to have DDS, were examined. The patients’ age was 64±7.4 years. Women (n = 10 more often developed DDS than men (n = 6. The patients mainly suffered from the mixed form of the disease. Stages III and IV were diagnosed in 72 and 22%, respectively. The duration of PD was 12+2.6 years. In the PD patients with DDS, the quality-of-life indicators ranged from 19.8 to 90% (54+20.1%. The equivalent dose of levodopa is 1323.4+299 mg/day. DDS was concurrent with other types of ICD in 4 patients: panding in 2, compulsive shopping and punding in 1, and punding and hypersexuality. The doses of levodopa were corrected in patients receiving high doses of dopaminergic drugs. In the patients with DDS concurrent with punding or hypersexuality, the dose of dopaminergic receptor agonists was gradually reduced and subsequently discontinued.

  10. Dysregulated Functions of Lung Macrophage Populations in COPD

    Science.gov (United States)

    Bassler, Kevin; Aschenbrenner, Anna C.

    2018-01-01

    Chronic obstructive pulmonary disease (COPD) is a diverse respiratory disease characterised by bronchiolitis, small airway obstruction, and emphysema. Innate immune cells play a pivotal role in the disease's progression, and in particular, lung macrophages exploit their prevalence and strategic localisation to orchestrate immune responses. To date, alveolar and interstitial resident macrophages as well as blood monocytes have been described in the lungs of patients with COPD contributing to disease pathology by changes in their functional repertoire. In this review, we summarise recent evidence from human studies and work with animal models of COPD with regard to altered functions of each of these myeloid cell populations. We primarily focus on the dysregulated capacity of alveolar macrophages to secrete proinflammatory mediators and proteases, induce oxidative stress, engulf microbes and apoptotic cells, and express surface and intracellular markers in patients with COPD. In addition, we discuss the differences in the responses between alveolar macrophages and interstitial macrophages/monocytes in the disease and propose how the field should advance to better understand the implications of lung macrophage functions in COPD. PMID:29670919

  11. Role of Melanin in Melanocyte Dysregulation of Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Noah C. Jenkins

    2013-01-01

    Full Text Available We have recently reported a potential alternative tumor suppressor function for p16 relating to its capacity to regulate oxidative stress and observed that oxidative dysregulation in p16-depleted cells was most profound in melanocytes, compared to keratinocytes or fibroblasts. Moreover, in the absence of p16 depletion or exogenous oxidative insult, melanocytes exhibited significantly higher basal levels of reactive oxygen species (ROS than these other epidermal cell types. Given the role of oxidative stress in melanoma development, we speculated that this increased susceptibility of melanocytes to oxidative stress (and greater reliance on p16 for suppression of ROS may explain why genetic compromise of p16 is more commonly associated with predisposition to melanoma rather than other cancers. Here we show that the presence of melanin accounts for this differential oxidative stress in normal and p16-depleted melanocytes. Thus the presence of melanin in the skin appears to be a double-edged sword: it protects melanocytes as well as neighboring keratinocytes in the skin through its capacity to absorb UV radiation, but its synthesis in melanocytes results in higher levels of intracellular ROS that may increase melanoma susceptibility.

  12. Classifier Directed Data Hybridization for Geographic Sample Supervised Segment Generation

    Directory of Open Access Journals (Sweden)

    Christoff Fourie

    2014-11-01

    Full Text Available Quality segment generation is a well-known challenge and research objective within Geographic Object-based Image Analysis (GEOBIA. Although methodological avenues within GEOBIA are diverse, segmentation commonly plays a central role in most approaches, influencing and being influenced by surrounding processes. A general approach using supervised quality measures, specifically user provided reference segments, suggest casting the parameters of a given segmentation algorithm as a multidimensional search problem. In such a sample supervised segment generation approach, spatial metrics observing the user provided reference segments may drive the search process. The search is commonly performed by metaheuristics. A novel sample supervised segment generation approach is presented in this work, where the spectral content of provided reference segments is queried. A one-class classification process using spectral information from inside the provided reference segments is used to generate a probability image, which in turn is employed to direct a hybridization of the original input imagery. Segmentation is performed on such a hybrid image. These processes are adjustable, interdependent and form a part of the search problem. Results are presented detailing the performances of four method variants compared to the generic sample supervised segment generation approach, under various conditions in terms of resultant segment quality, required computing time and search process characteristics. Multiple metrics, metaheuristics and segmentation algorithms are tested with this approach. Using the spectral data contained within user provided reference segments to tailor the output generally improves the results in the investigated problem contexts, but at the expense of additional required computing time.

  13. Repeated verum but not placebo acupuncture normalizes connectivity in brain regions dysregulated in chronic pain

    Directory of Open Access Journals (Sweden)

    Natalia Egorova

    2015-01-01

    Full Text Available Acupuncture, an ancient East Asian therapy, is aimed at rectifying the imbalance within the body caused by disease. Studies evaluating the efficacy of acupuncture with neuroimaging tend to concentrate on brain regions within the pain matrix, associated with acute pain. We, however, focused on the effect of repeated acupuncture treatment specifically on brain regions known to support functions dysregulated in chronic pain disorders. Transition to chronic pain is associated with increased attention to pain, emotional rumination, nociceptive memory and avoidance learning, resulting in brain connectivity changes, specifically affecting the periaqueductal gray (PAG, medial frontal cortex (MFC and bilateral hippocampus (Hpc. We demonstrate that the PAG–MFC and PAG–Hpc connectivity in patients with chronic pain due to knee osteoarthritis indeed correlates with clinical severity scores and further show that verum acupuncture-induced improvement in pain scores (compared to sham is related to the modulation of PAG–MFC and PAG–Hpc connectivity in the predicted direction. This study shows that repeated verum acupuncture might act by restoring the balance in the connectivity of the key pain brain regions, altering pain-related attention and memory.

  14. Pancreatic Islet Protein Complexes and Their Dysregulation in Type 2 Diabetes

    DEFF Research Database (Denmark)

    Pedersen, Helle Krogh; Gudmundsdottir, Valborg; Brunak, Søren

    2017-01-01

    Type 2 diabetes (T2D) is a complex disease that involves multiple genes. Numerous risk loci have already been associated with T2D, although many susceptibility genes remain to be identified given heritability estimates. Systems biology approaches hold potential for discovering novel T2D genes by ...... starting point when evaluating an individual's alterations at the genome, transcriptome, or proteome level in relation to T2D in clinical settings.......Type 2 diabetes (T2D) is a complex disease that involves multiple genes. Numerous risk loci have already been associated with T2D, although many susceptibility genes remain to be identified given heritability estimates. Systems biology approaches hold potential for discovering novel T2D genes...... by considering their biological context, such as tissue-specific protein interaction partners. Pancreatic islets are a key T2D tissue and many of the known genetic risk variants lead to impaired islet function, hence a better understanding of the islet-specific dysregulation in the disease-state is essential...

  15. Serum proteomics reveals systemic dysregulation of innate immunity in type 1 diabetes

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Qibin; Fillmore, Thomas L.; Schepmoes, Athena A.; Clauss, Therese RW; Gritsenko, Marina A.; Mueller, Patricia W.; Rewers, Marian; Atkinson, Mark A.; Smith, Richard D.; Metz, Thomas O.

    2013-01-14

    Using global liquid chromatography-mass spectrometry (LC-MS)-based proteomics analyses, we identified 24 serum proteins significantly variant between those with type 1 diabetes and healthy controls. Functionally, these proteins represent innate immune responses, the activation cascade of complement, inflammatory responses and blood coagulation. Targeted verification analyses were performed on 52 surrogate peptides representing these proteins with serum samples from an antibody standardization program cohort of 100 healthy control and 50 type 1 diabetic subjects, and 16 peptides were verified having very good discriminating power, with areas under the receiver operator characteristic curve ≥ 0.8. Further validation with blinded serum samples from an independent cohort (10 healthy control and 10 type 1 diabetic) demonstrated that peptides from platelet basic protein and C1 inhibitor achieved both 100% sensitivity and 100% specificity for classification of samples. The disease specificity of these proteins was assessed using serum from 50 age matched type 2 diabetic individuals, and a subset of proteins, particularly C1 inhibitor were exceptionally good discriminators between these two forms of diabetes. The panel of biomarkers distinguishing those with type 1 diabetes from healthy control and type 2 diabetes suggests dysregulated innate immune responses may be associated with the development of this disorder.

  16. Market segmentation: Venezuelan ADRs

    Directory of Open Access Journals (Sweden)

    Urbi Garay

    2012-12-01

    Full Text Available The control on foreign exchange imposed by Venezuela in 2003 constitute a natural experiment that allows researchers to observe the effects of exchange controls on stock market segmentation. This paper provides empirical evidence that although the Venezuelan capital market as a whole was highly segmented before the controls were imposed, the shares in the firm CANTV were, through their American Depositary Receipts (ADRs, partially integrated with the global market. Following the imposition of the exchange controls this integration was lost. Research also documents the spectacular and apparently contradictory rise experienced by the Caracas Stock Exchange during the serious economic crisis of 2003. It is argued that, as it happened in Argentina in 2002, the rise in share prices occurred because the depreciation of the Bolívar in the parallel currency market increased the local price of the stocks that had associated ADRs, which were negotiated in dollars.

  17. Scintillation counter, segmented shield

    International Nuclear Information System (INIS)

    Olson, R.E.; Thumim, A.D.

    1975-01-01

    A scintillation counter, particularly for counting gamma ray photons, includes a massive lead radiation shield surrounding a sample-receiving zone. The shield is disassembleable into a plurality of segments to allow facile installation and removal of a photomultiplier tube assembly, the segments being so constructed as to prevent straight-line access of external radiation through the shield into radiation-responsive areas. Provisions are made for accurately aligning the photomultiplier tube with respect to one or more sample-transmitting bores extending through the shield to the sample receiving zone. A sample elevator, used in transporting samples into the zone, is designed to provide a maximum gamma-receiving aspect to maximize the gamma detecting efficiency. (U.S.)

  18. NASA 14 Day Undersea Missions: A Short-Duration Spaceflight Analog for Immune System Dysregulation

    Science.gov (United States)

    Crucian, B. E.; Stowe, R. P.; Mehta, S. K.; Quiriarte, H.; Pierson, D. L.; Sams, C. F.

    2010-01-01

    BACKGROUND Spaceflight-associated immune dysregulation (SAID) occurs during spaceflight and may represent specific clinical risks for exploration-class missions. An appropriate ground analog for spaceflight-associated immune dysregulation would offer a platform for ground-evaluation of various potential countermeasures. This study evaluated the NASA Undersea Mission Operations ( NEEMO ), consisting of 14 day undersea deployment at the Aquarius station, as an analog for SAID. Sixteen Aquanauts from missions NEEMO-12, 13 and 14 participated in the study. RESULTS Mid-mission alterations leukocyte distribution occurred, including granulocytosis and elevations in central-memory CD8+ T-cells. General T cell function was reduced during NEEMO missions in roughly 50% of subjects. Secreted cytokines profiles were evaluated following whole blood stimulation with CD3/CD28 (T cells) or LPS (monocytes). T cell production of IFNg, IL-5, IL-10, IL-2, TNFa and IL-6 were all reduced before and during the mission. Conversely, monocyte production of TNFa, IL-10, IL-6, IL-1b and IL-8 were elevated during mission, moreso at the MD-14 timepoint. Antibodies to Epstein-Barr virus (EBV) viral capsid antigen and early antigen were increased in approximately 40% of the subjects. Changes in EBV tetramer-positive CD8+ T-cells exhibited a variable pattern. Antibodies against Cytomegalovirus (CMV) were marginally increased during the mission. Herpesvirus reactivation was determined by PCR. EBV viral load was generally elevated at L-6. Higher levels of salivary EBV were found during the NEEMO mission than before and after as well as than the healthy controls. No VZV or CMV was found in any pre, during and after NEEMO mission or control samples. Plasma cortisol was elevated at L-6. CONCLUSION Unfortunately, L-6 may be too near to mission start to be an appropriate baseline measurement. The general immune changes in leukocyte distribution, T cell function, cytokine production, virus specific

  19. Head segmentation in vertebrates

    OpenAIRE

    Kuratani, Shigeru; Schilling, Thomas

    2008-01-01

    Classic theories of vertebrate head segmentation clearly exemplify the idealistic nature of comparative embryology prior to the 20th century. Comparative embryology aimed at recognizing the basic, primary structure that is shared by all vertebrates, either as an archetype or an ancestral developmental pattern. Modern evolutionary developmental (Evo-Devo) studies are also based on comparison, and therefore have a tendency to reduce complex embryonic anatomy into overly simplified patterns. Her...

  20. Strategies for regular segmented reductions on GPU

    DEFF Research Database (Denmark)

    Larsen, Rasmus Wriedt; Henriksen, Troels

    2017-01-01

    We present and evaluate an implementation technique for regular segmented reductions on GPUs. Existing techniques tend to be either consistent in performance but relatively inefficient in absolute terms, or optimised for specific workloads and thereby exhibiting bad performance for certain input...... is in the context of the Futhark compiler, the implementation technique is applicable to any library or language that has a need for segmented reductions. We evaluate the technique on four microbenchmarks, two of which we also compare to implementations in the CUB library for GPU programming, as well as on two...

  1. Video segmentation using keywords

    Science.gov (United States)

    Ton-That, Vinh; Vong, Chi-Tai; Nguyen-Dao, Xuan-Truong; Tran, Minh-Triet

    2018-04-01

    At DAVIS-2016 Challenge, many state-of-art video segmentation methods achieve potential results, but they still much depend on annotated frames to distinguish between background and foreground. It takes a lot of time and efforts to create these frames exactly. In this paper, we introduce a method to segment objects from video based on keywords given by user. First, we use a real-time object detection system - YOLOv2 to identify regions containing objects that have labels match with the given keywords in the first frame. Then, for each region identified from the previous step, we use Pyramid Scene Parsing Network to assign each pixel as foreground or background. These frames can be used as input frames for Object Flow algorithm to perform segmentation on entire video. We conduct experiments on a subset of DAVIS-2016 dataset in half the size of its original size, which shows that our method can handle many popular classes in PASCAL VOC 2012 dataset with acceptable accuracy, about 75.03%. We suggest widely testing by combining other methods to improve this result in the future.

  2. Autoimmunity and autoinflammation: A systems view on signaling pathway dysregulation profiles.

    Directory of Open Access Journals (Sweden)

    Arsen Arakelyan

    Full Text Available Autoinflammatory and autoimmune disorders are characterized by aberrant changes in innate and adaptive immunity that may lead from an initial inflammatory state to an organ specific damage. These disorders possess heterogeneity in terms of affected organs and clinical phenotypes. However, despite the differences in etiology and phenotypic variations, they share genetic associations, treatment responses and clinical manifestations. The mechanisms involved in their initiation and development remain poorly understood, however the existence of some clear similarities between autoimmune and autoinflammatory disorders indicates variable degrees of interaction between immune-related mechanisms.Our study aims at contributing to a holistic, pathway-centered view on the inflammatory condition of autoimmune and autoinflammatory diseases. We have evaluated similarities and specificities of pathway activity changes in twelve autoimmune and autoinflammatory disorders by performing meta-analysis of publicly available gene expression datasets generated from peripheral blood mononuclear cells, using a bioinformatics pipeline that integrates Self Organizing Maps and Pathway Signal Flow algorithms along with KEGG pathway topologies.The results reveal that clinically divergent disease groups share common pathway perturbation profiles. We identified pathways, similarly perturbed in all the studied diseases, such as PI3K-Akt, Toll-like receptor, and NF-kappa B signaling, that serve as integrators of signals guiding immune cell polarization, migration, growth, survival and differentiation. Further, two clusters of diseases were identified based on specifically dysregulated pathways: one gathering mostly autoimmune and the other mainly autoinflammatory diseases. Cluster separation was driven not only by apparent involvement of pathways implicated in adaptive immunity in one case, and inflammation in the other, but also by processes not explicitly related to immune

  3. Purchase decision involvement: Event management segments and related event behavior

    Science.gov (United States)

    Rodney B. Warnick; David C. Bojanic

    2012-01-01

    The goal of this research was to examine the relationships between different levels of event purchase decision involvement (PDI) segments and their respective event behaviors (e.g., expenditures, travel behavior, event consumption and satisfaction). The specific purpose was to answer two major research questions: 1) Can PDI identify different levels or segments of...

  4. Cochlea Segmentation using Iterated Random Walks with Shape Prior

    DEFF Research Database (Denmark)

    Ruiz Pujadas, Esmeralda; Kjer, Hans Martin; Vera, Sergio

    2016-01-01

    Cochlear implants can restore hearing to deaf or partially deaf patients. In order to plan the intervention, a model from high resolution μCT images is to be built from accurate cochlea segmentations and then, adapted to a patient-specific model. Thus, a precise segmentation is required to build...

  5. Market segmentation in behavioral perspective.

    OpenAIRE

    Wells, V.K.; Chang, S.W.; Oliveira-Castro, J.M.; Pallister, J.

    2010-01-01

    A segmentation approach is presented using both traditional demographic segmentation bases (age, social class/occupation, and working status) and a segmentation by benefits sought. The benefits sought in this case are utilitarian and informational reinforcement, variables developed from the Behavioral Perspective Model (BPM). Using data from 1,847 consumers and from a total of 76,682 individual purchases, brand choice and price and reinforcement responsiveness were assessed for each segment a...

  6. Systematic identification of core transcription factors mediating dysregulated links bridging inflammatory bowel diseases and colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Yun Xiao

    Full Text Available Accumulating evidence shows a tight link between inflammation and cancer. However, comprehensive identification of pivotal transcription factors (i.e., core TFs mediating the dysregulated links remains challenging, mainly due to a lack of samples that can effectively reflect the connections between inflammation and tumorigenesis. Here, we constructed a series of TF-mediated regulatory networks from a large compendium of expression profiling of normal colonic tissues, inflammatory bowel diseases (IBDs and colorectal cancer (CRC, which contains 1201 samples in total, and then proposed a network-based approach to characterize potential links bridging inflammation and cancer. For this purpose, we computed significantly dysregulated relationships between inflammation and their linked cancer networks, and then 24 core TFs with their dysregulated genes were identified. Collectively, our approach provides us with quite important insight into inflammation-associated tumorigenesis in colorectal cancer, which could also be applied to identify functionally dysregulated relationships mediating the links between other different disease phenotypes.

  7. Depressive Symptoms, Emotion Dysregulation, and Bulimic Symptoms in Youth With Type 1 Diabetes

    Science.gov (United States)

    Young-Hyman, Deborah L.; Peterson, Claire M.; Fischer, Sarah; Markowitz, Jessica T.; Muir, Andrew B.; Laffel, Lori M.

    2016-01-01

    This study evaluated the associations between depressive symptoms, emotion dysregulation and bulimic symptoms in youth with type 1 diabetes (T1D) in the context of the diagnosis and treatment of T1D. Study participants were 103 youth in 2 distinct groups: newly diagnosed (New) or transitioning to pump therapy (continuous subcutaneous insulin infusion [CSII]; “Pump”), who completed questionnaires regarding symptoms of depression, emotion dysregulation, and bulimia. Glycemic control (A1c), height, weight, and questionnaires were evaluated within 10 days of diagnosis (n = 58) or at education/clinic visit before starting insulin utilizing CSII (n = 45). In the newly diagnosed group, only depression accounted for significant variance in bulimia scores (β = .47, P symptoms and emotion dysregulation were associated with greater bulimic symptoms. Depressive symptoms and emotion dysregulation, an indicator of poor coping/behavioral control, could help explain adoption of disordered eating behaviors in youth with T1D who are transitioning to pump therapy. PMID:27137457

  8. Segmenting the Adult Education Market.

    Science.gov (United States)

    Aurand, Tim

    1994-01-01

    Describes market segmentation and how the principles of segmentation can be applied to the adult education market. Indicates that applying segmentation techniques to adult education programs results in programs that are educationally and financially satisfying and serve an appropriate population. (JOW)

  9. Market Segmentation for Information Services.

    Science.gov (United States)

    Halperin, Michael

    1981-01-01

    Discusses the advantages and limitations of market segmentation as strategy for the marketing of information services made available by nonprofit organizations, particularly libraries. Market segmentation is defined, a market grid for libraries is described, and the segmentation of information services is outlined. A 16-item reference list is…

  10. NASA 14 Day Undersea Missions: A Short-Duration Spaceflight Analog for Immune System Dysregulation?

    Science.gov (United States)

    Crucian, B. E.; Stowe, R. P.; Mehta, S. K.; Chouker, A.; Feuerecker, M.; Quiriarte, H.; Pierson, D. L.; Sams, C. F.

    2011-01-01

    This poster paper reviews the use of 14 day undersea missions as a possible analog for short duration spaceflight for the study of immune system dysregulation. Sixteen subjects from the the NASA Extreme Enviro nment Mission Operations (NEEMO) 12, 13 and 14 missions were studied for immune system dysregulation. The assays that are presented in this poster are the Virleukocyte subsets, the T Cell functions, and the intracellular/secreted cytokine profiles. Other assays were performed, but are not included in this presntation.

  11. Does Emotion Dysregulation Mediate the Association Between Sluggish Cognitive Tempo and College Students' Social Impairment?

    Science.gov (United States)

    Flannery, Andrew J; Becker, Stephen P; Luebbe, Aaron M

    2016-09-01

    Studies demonstrate an association between sluggish cognitive tempo (SCT) and social impairment, although no studies have tested possible mechanisms of this association. This study aimed to (a) examine SCT in relation to college students' social functioning; (b) test if SCT is significantly associated with emotion dysregulation beyond depressive, anxious, and ADHD symptoms; and (c) test if emotion dysregulation mediates the association between SCT symptoms and social impairment. College students (N = 158) completed measures of psychopathology symptoms, emotion dysregulation, and social functioning. Participants with elevated SCT (12%) had higher ADHD, depressive, and anxious symptoms in addition to poorer emotion regulation and social adjustment than participants without elevated SCT. Above and beyond other psychopathologies, SCT was significantly associated with social impairment but not general interpersonal functioning. SCT was also associated with emotion dysregulation, even after accounting for the expectedly strong association between depression and emotion dysregulation. Further analyses supported emotion dysregulation as a mediator of the association between SCT and social impairment. These findings are important for theoretical models of SCT and underscore the need for additional, longitudinal research. © The Author(s) 2014.

  12. Dysregulated autophagy contributes to podocyte damage in Fabry's disease.

    Directory of Open Access Journals (Sweden)

    Max C Liebau

    Full Text Available Fabry's disease results from an inborn error of glycosphingolipid metabolism that is due to deficiency of the lysosomal hydrolase α-galactosidase A. This X-linked defect results in the accumulation of enzyme substrates with terminally α-glycosidically bound galactose, mainly the neutral glycosphingolipid Globotriaosylceramide (Gb3 in various tissues, including the kidneys. Although end-stage renal disease is one of the most common causes of death in hemizygous males with Fabry's disease, the pathophysiology leading to proteinuria, hematuria, hypertension, and kidney failure is not well understood. Histological studies suggest that the accumulation of Gb3 in podocytes plays an important role in the pathogenesis of glomerular damage. However, due to the lack of appropriate animal or cellular models, podocyte damage in Fabry's disease could not be directly studied yet. As murine models are insufficient, a human model is needed. Here, we developed a human podocyte model of Fabry's disease by combining RNA interference technology with lentiviral transduction of human podocytes. Knockdown of α-galactosidase A expression resulted in diminished enzymatic activity and slowly progressive accumulation of intracellular Gb3. Interestingly, these changes were accompanied by an increase in autophagosomes as indicated by an increased abundance of LC3-II and a loss of mTOR kinase activity, a negative regulator of the autophagic machinery. These data suggest that dysregulated autophagy in α-galactosidase A-deficient podocytes may be the result of deficient mTOR kinase activity. This finding links the lysosomal enzymatic defect in Fabry's disease to deregulated autophagy pathways and provides a promising new direction for further studies on the pathomechanism of glomerular injury in Fabry patients.

  13. Dysregulation of Macrophage Activation Profiles by Engineered Nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Kodali, Vamsi; Littke, Matthew H.; Tilton, Susan C.; Teeguarden, Justin G.; Shi, Liang; Frevert, Charles W.; Wang, Wei; Pounds, Joel G.; Thrall, Brian D.

    2013-08-27

    Although the potential human health impacts from exposure to engineered nanoparticles (ENPs) are uncertain, past epidemiological studies have established correlations between exposure to ambient air pollution particulates and the incidence of pneumonia and lung infections. Using amorphous silica and superparamagnetic iron oxide (SPIO) as model high production volume ENPs, we examined how macrophage activation by bacterial lipopolysaccharide (LPS) or the lung pathogen Streptococcus pneumoniae is altered by ENP pretreatment. Neither silica nor SPIO treatment elicited direct cytotoxic or pro-inflammatory effects in bone marrow-derived macrophages. However, pretreatment of macrophages with SPIO caused extensive reprogramming of nearly 500 genes regulated in response to LPS challenge, hallmarked by exaggerated activation of oxidative stress response pathways and suppressed activation of both pro- and anti-inflammatory pathways. Silica pretreatment altered regulation of only 67 genes, but there was strong correlation with gene sets affected by SPIO. Macrophages exposed to SPIO displayed a phenotype suggesting an impaired ability to transition from an M1 to M2-like activation state, characterized by suppressed IL-10 induction, enhanced TNFα production, and diminished phagocytic activity toward S. pneumoniae. Studies in macrophages deficient in scavenger receptor A (SR-A) showed SR-A participates in cell uptake of both the ENPs and S. pneumonia and co-regulates the anti-inflammatory IL-10 pathway. Thus, mechanisms for dysregulation of innate immunity exist by virtue that common receptor recognition pathways are used by some ENPs and pathogenic bacteria, although the extent of transcriptional reprogramming of macrophage function depends on the physicochemical properties of the ENP after internalization. Our results also illustrate that biological effects of ENPs may be indirectly manifested only after challenging normal cell function. Finally, nanotoxicology screening

  14. Dysregulated physiological stress systems and accelerated cellular aging.

    Science.gov (United States)

    Révész, Dóra; Verhoeven, Josine E; Milaneschi, Yuri; de Geus, Eco J C N; Wolkowitz, Owen M; Penninx, Brenda W J H

    2014-06-01

    Exposure to chronic stressors is associated with accelerated biological aging as indicated by reduced leukocyte telomere length (LTL). This impact could be because of chronic overactivation of the body's physiological stress systems. This study examined the associations between LTL and the immune system, hypothalamic-pituitary-adrenal axis and autonomic nervous system. LTL was assessed in 2936 adults from the Netherlands Study of Depression and Anxiety. Inflammation markers (interleukin-6, c-reactive protein, tumor necrosis factor-alpha), hypothalamic-pituitary-adrenal-axis indicators (salivary cortisol awakening curve [area under the curve indicators, with respect to the ground and increase], evening levels, 0.5 mg dexamethasone cortisol suppression ratio), and autonomic nervous system measures (heart rate, respiratory sinus arrhythmia, pre-ejection period) were determined. Linear regression analyses were performed and adjusted for sociodemographic, lifestyle and clinical factors. Shorter LTL was significantly associated with higher c-reactive protein, interleukin-6, area under the curve with respect to increase, and heart rate. A cumulative index score was calculated based on the number of highest tertiles of these 4 stress markers. LTL demonstrated a significant gradient within subjects ranging from having zero (5528 base pairs) to having 4 elevated stress markers (5371 base pairs, p for trend = 0.002), corresponding to a difference of 10 years of accelerated biological aging. Contrary to the expectations, shorter LTL was also associated with longer pre-ejection period, indicating lower sympathetic tone. This large-scale study showed that inflammation, high awakening cortisol response, and increased heart rate are associated with shorter LTL, especially when they are dysregulated cumulatively. Copyright © 2014 Elsevier Inc. All rights reserved.

  15. Angiogenesis dysregulation in term asphyxiated newborns treated with hypothermia.

    Directory of Open Access Journals (Sweden)

    Henna Shaikh

    Full Text Available Neonatal encephalopathy following birth asphyxia is a major predictor of long-term neurological impairment. Therapeutic hypothermia is currently the standard of care to prevent brain injury in asphyxiated newborns but is not protective in all cases. More robust and versatile treatment options are needed. Angiogenesis is a demonstrated therapeutic target in adult stroke. However, no systematic study examines the expression of angiogenesis-related markers following birth asphyxia in human newborns.This study aimed to evaluate the expression of angiogenesis-related protein markers in asphyxiated newborns developing and not developing brain injury compared to healthy control newborns.Twelve asphyxiated newborns treated with hypothermia were prospectively enrolled; six developed eventual brain injury and six did not. Four healthy control newborns were also included. We used Rules-Based Medicine multi-analyte profiling and protein array technologies to study the plasma concentration of 49 angiogenesis-related proteins. Mean protein concentrations were compared between each group of newborns.Compared to healthy newborns, asphyxiated newborns not developing brain injury showed up-regulation of pro-angiogenic proteins, including fatty acid binding protein-4, glucose-6-phosphate isomerase, neuropilin-1, and receptor tyrosine-protein kinase erbB-3; this up-regulation was not evident in asphyxiated newborns eventually developing brain injury. Also, asphyxiated newborns developing brain injury showed a decreased expression of anti-angiogenic proteins, including insulin-growth factor binding proteins -1, -4, and -6, compared to healthy newborns.These findings suggest that angiogenesis pathways are dysregulated following birth asphyxia and are putatively involved in brain injury pathology and recovery.

  16. Angiogenesis Dysregulation in Term Asphyxiated Newborns Treated with Hypothermia

    Science.gov (United States)

    Shaikh, Henna; Boudes, Elodie; Khoja, Zehra; Shevell, Michael; Wintermark, Pia

    2015-01-01

    Background Neonatal encephalopathy following birth asphyxia is a major predictor of long-term neurological impairment. Therapeutic hypothermia is currently the standard of care to prevent brain injury in asphyxiated newborns but is not protective in all cases. More robust and versatile treatment options are needed. Angiogenesis is a demonstrated therapeutic target in adult stroke. However, no systematic study examines the expression of angiogenesis-related markers following birth asphyxia in human newborns. Objective This study aimed to evaluate the expression of angiogenesis-related protein markers in asphyxiated newborns developing and not developing brain injury compared to healthy control newborns. Design/Methods Twelve asphyxiated newborns treated with hypothermia were prospectively enrolled; six developed eventual brain injury and six did not. Four healthy control newborns were also included. We used Rules-Based Medicine multi-analyte profiling and protein array technologies to study the plasma concentration of 49 angiogenesis-related proteins. Mean protein concentrations were compared between each group of newborns. Results Compared to healthy newborns, asphyxiated newborns not developing brain injury showed up-regulation of pro-angiogenic proteins, including fatty acid binding protein-4, glucose-6-phosphate isomerase, neuropilin-1, and receptor tyrosine-protein kinase erbB-3; this up-regulation was not evident in asphyxiated newborns eventually developing brain injury. Also, asphyxiated newborns developing brain injury showed a decreased expression of anti-angiogenic proteins, including insulin-growth factor binding proteins -1, -4, and -6, compared to healthy newborns. Conclusions These findings suggest that angiogenesis pathways are dysregulated following birth asphyxia and are putatively involved in brain injury pathology and recovery. PMID:25996847

  17. Power spectrum scale invariance identifies prefrontal dysregulation in paranoid schizophrenia.

    Science.gov (United States)

    Radulescu, Anca R; Rubin, Denis; Strey, Helmut H; Mujica-Parodi, Lilianne R

    2012-07-01

    Theory and experimental evidence suggest that complex living systems function close to the boundary of chaos, with erroneous organization to an improper dynamical range (too stiff or chaotic) underlying system-wide dysregulation and disease. We hypothesized that erroneous organization might therefore also characterize paranoid schizophrenia, via optimization abnormalities in the prefrontal-limbic circuit regulating emotion. To test this, we acquired fMRI scans from 35 subjects (N = 9 patients with paranoid schizophrenia and N = 26 healthy controls), while they viewed affect-valent stimuli. To quantify dynamic regulation, we analyzed the power spectrum scale invariance (PSSI) of fMRI time-courses and computed the geometry of time-delay (Poincaré) maps, a measure of variability. Patients and controls showed distinct PSSI in two clusters (k(1) : Z = 4.3215, P = 0.00002 and k(2) : Z = 3.9441, P = 0.00008), localized to the orbitofrontal/medial prefrontal cortex (Brodmann Area 10), represented by β close to white noise in patients (β ≈ 0) and in the pink noise range in controls (β ≈ -1). Interpreting the meaning of PSSI differences, the Poincaré maps indicated less variability in patients than controls (Z = -1.9437, P = 0.05 for k(1) ; Z = -2.5099, P = 0.01 for k(2) ). That the dynamics identified Brodmann Area 10 is consistent with previous schizophrenia research, which implicates this area in deficits of working memory, executive functioning, emotional regulation and underlying biological abnormalities in synaptic (glutamatergic) transmission. Our results additionally cohere with a large body of work finding pink noise to be the normal range of central function at the synaptic, cellular, and small network levels, and suggest that patients show less supple responsivity of this region. Copyright © 2011 Wiley-Liss, Inc.

  18. Emotional dysregulation in borderline personality disorder and its influence on communication behavior and feelings in romantic relationships.

    Science.gov (United States)

    Miano, Annemarie; Grosselli, Luna; Roepke, Stefan; Dziobek, Isabel

    2017-08-01

    Dysfunction in romantic relationships constitutes one of the most burdensome symptoms of borderline personality disorder (BPD). The aim of this study was to ascertain how emotional dysregulation affects behavior and relationship related feelings of women with BPD in threatening conversations with their own romantic partner. Thirty couples in which the women were diagnosed with BPD and 34 healthy control (HC) couples were videotaped while discussing personally threatening (i.e., personal failure) and relationship-threatening (i.e., separation) themes. Third party raters evaluated stress and communication behaviors during the conversations. Relationship related feelings, i.e., closeness and relationship insecurity, were assessed by self-report. Overall, women with BPD were rated as more stressed in threatening situations than HC women and their partners, but not more stressed in relationship-threatening than personally threatening situations. A heightened stress response of women with BPD predicted more negative and less positive communication behaviors and a stronger decline in self-rated closeness to the partner compared to HC. Stress-induced increases in relationship insecurity were specific to women with BPD. Our results highlight the central role of emotional dysregulation in interpersonal dysfunctions of persons with BPD and the need to address individual emotion regulation strategies more explicitly in dyadic contexts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Abnormalities of thymic stroma may contribute to immune dysregulation in murine models of leaky severe combined immunodeficiency

    Directory of Open Access Journals (Sweden)

    Francesca eRucci

    2011-05-01

    Full Text Available Lymphostromal cross-talk in the thymus is essential to allow generation of a diversified repertoire of T lymphocytes and to prevent autoimmunity by self-reactive T cells. Hypomorphic mutations in genes that control T cell development have been associated with immunodeficiency and immune dysregulation both in humans and in mice. We have studied T cell development and thymic stroma architecture and maturation in two mouse models of leaky SCID, carrying hypomorphic mutations in Rag1 and Lig4 genes. Defective T cell development was associated with abnormalities of thymic architecture that predominantly affect the thymic medulla, with reduction of the pool of mature medullary thymic epithelial cells (mTECs. While the ability of mTECs to express Aire is preserved in mutant mice, the frequency of mature mTECs expressing Aire and tissue-specific antigens (TSAs is severely reduced. Similarly, the ability of CD4+ T cells to differentiate into Foxp3+ natural regulatory T cells is preserved in Rag1 and Lig4 mutant mice, but their number is greatly reduced. These data indicate that hypomorphic defects in T cell development may cause defective lymphostromal cross-talk and impinge on thymic stromal cells maturation, and thus favor immune dysregulation.

  20. Identifying mRNA targets of microRNA dysregulated in cancer: with application to clear cell Renal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Liou Louis S

    2010-04-01

    Full Text Available Abstract Background MicroRNA regulate mRNA levels in a tissue specific way, either by inducing degradation of the transcript or by inhibiting translation or transcription. Putative mRNA targets of microRNA identified from seed sequence matches are available in many databases. However, such matches have a high false positive rate and cannot identify tissue specificity of regulation. Results We describe a simple method to identify direct mRNA targets of microRNA dysregulated in cancers from expression level measurements in patient matched tumor/normal samples. The word "direct" is used here in a strict sense to: a represent mRNA which have an exact seed sequence match to the microRNA in their 3'UTR, b the seed sequence match is strictly conserved across mouse, human, rat and dog genomes, c the mRNA and microRNA expression levels can distinguish tumor from normal with high significance and d the microRNA/mRNA expression levels are strongly and significantly anti-correlated in tumor and/or normal samples. We apply and validate the method using clear cell Renal Cell Carcinoma (ccRCC and matched normal kidney samples, limiting our analysis to mRNA targets which undergo degradation of the mRNA transcript because of a perfect seed sequence match. Dysregulated microRNA and mRNA are first identified by comparing their expression levels in tumor vs normal samples. Putative dysregulated microRNA/mRNA pairs are identified from these using seed sequence matches, requiring that the seed sequence be conserved in human/dog/rat/mouse genomes. These are further pruned by requiring a strong anti-correlation signature in tumor and/or normal samples. The method revealed many new regulations in ccRCC. For instance, loss of miR-149, miR-200c and mir-141 causes gain of function of oncogenes (KCNMA1, LOX, VEGFA and SEMA6A respectively and increased levels of miR-142-3p, miR-185, mir-34a, miR-224, miR-21 cause loss of function of tumor suppressors LRRC2, PTPN13, SFRP1

  1. Albedo estimation for scene segmentation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, C H; Rosenfeld, A

    1983-03-01

    Standard methods of image segmentation do not take into account the three-dimensional nature of the underlying scene. For example, histogram-based segmentation tacitly assumes that the image intensity is piecewise constant, and this is not true when the scene contains curved surfaces. This paper introduces a method of taking 3d information into account in the segmentation process. The image intensities are adjusted to compensate for the effects of estimated surface orientation; the adjusted intensities can be regarded as reflectivity estimates. When histogram-based segmentation is applied to these new values, the image is segmented into parts corresponding to surfaces of constant reflectivity in the scene. 7 references.

  2. FRAMEWORK FOR COMPARING SEGMENTATION ALGORITHMS

    Directory of Open Access Journals (Sweden)

    G. Sithole

    2015-05-01

    Full Text Available The notion of a ‘Best’ segmentation does not exist. A segmentation algorithm is chosen based on the features it yields, the properties of the segments (point sets it generates, and the complexity of its algorithm. The segmentation is then assessed based on a variety of metrics such as homogeneity, heterogeneity, fragmentation, etc. Even after an algorithm is chosen its performance is still uncertain because the landscape/scenarios represented in a point cloud have a strong influence on the eventual segmentation. Thus selecting an appropriate segmentation algorithm is a process of trial and error. Automating the selection of segmentation algorithms and their parameters first requires methods to evaluate segmentations. Three common approaches for evaluating segmentation algorithms are ‘goodness methods’, ‘discrepancy methods’ and ‘benchmarks’. Benchmarks are considered the most comprehensive method of evaluation. This paper shortcomings in current benchmark methods are identified and a framework is proposed that permits both a visual and numerical evaluation of segmentations for different algorithms, algorithm parameters and evaluation metrics. The concept of the framework is demonstrated on a real point cloud. Current results are promising and suggest that it can be used to predict the performance of segmentation algorithms.

  3. Dysregulation of C-X-C motif ligand 10 during aging and association with cognitive performance.

    Science.gov (United States)

    Bradburn, Steven; McPhee, Jamie; Bagley, Liam; Carroll, Michael; Slevin, Mark; Al-Shanti, Nasser; Barnouin, Yoann; Hogrel, Jean-Yves; Pääsuke, Mati; Gapeyeva, Helena; Maier, Andrea; Sipilä, Sarianna; Narici, Marco; Robinson, Andrew; Mann, David; Payton, Antony; Pendleton, Neil; Butler-Browne, Gillian; Murgatroyd, Chris

    2018-03-01

    Chronic low-grade inflammation during aging (inflammaging) is associated with cognitive decline and neurodegeneration; however, the mechanisms underlying inflammaging are unclear. We studied a population (n = 361) of healthy young and old adults from the MyoAge cohort. Peripheral levels of C-X-C motif chemokine ligand 10 (CXCL10) was found to be higher in older adults, compared with young, and negatively associated with working memory performance. This coincided with an age-related reduction in blood DNA methylation at specific CpGs within the CXCL10 gene promoter. In vitro analysis supported the role of DNA methylation in regulating CXCL10 transcription. A polymorphism (rs56061981) that altered methylation at one of these CpG sites further associated with working memory performance in 2 independent aging cohorts. Studying prefrontal cortex samples, we found higher CXCL10 protein levels in those with Alzheimer's disease, compared with aged controls. These findings support the association of peripheral inflammation, as demonstrated by CXCL10, in aging and cognitive decline. We reveal age-related epigenetic and genetic factors which contribute to the dysregulation of CXCL10. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Proteome analysis of schizophrenia patients Wernicke's area reveals an energy metabolism dysregulation

    Directory of Open Access Journals (Sweden)

    Marangoni Sérgio

    2009-04-01

    Full Text Available Abstract Background Schizophrenia is likely to be a consequence of DNA alterations that, together with environmental factors, will lead to protein expression differences and the ultimate establishment of the illness. The superior temporal gyrus is implicated in schizophrenia and executes functions such as the processing of speech, language skills and sound processing. Methods We performed an individual comparative proteome analysis using two-dimensional gel electrophoresis of 9 schizophrenia and 6 healthy control patients' left posterior superior temporal gyrus (Wernicke's area – BA22p identifying by mass spectrometry several protein expression alterations that could be related to the disease. Results Our analysis revealed 11 downregulated and 14 upregulated proteins, most of them related to energy metabolism. Whereas many of the identified proteins have been previously implicated in schizophrenia, such as fructose-bisphosphate aldolase C, creatine kinase and neuron-specific enolase, new putative disease markers were also identified such as dihydrolipoyl dehydrogenase, tropomyosin 3, breast cancer metastasis-suppressor 1, heterogeneous nuclear ribonucleoproteins C1/C2 and phosphate carrier protein, mitochondrial precursor. Besides, the differential expression of peroxiredoxin 6 (PRDX6 and glial fibrillary acidic protein (GFAP were confirmed by western blot in schizophrenia prefrontal cortex. Conclusion Our data supports a dysregulation of energy metabolism in schizophrenia as well as suggests new markers that may contribute to a better understanding of this complex disease.

  5. Placental adaptations to micronutrient dysregulation in the programming of chronic disease.

    Science.gov (United States)

    Hofstee, Pierre; McKeating, Daniel; Perkins, Anthony V; Cuffe, James S M

    2018-04-21

    Poor nutrition during pregnancy is known to impair foetal development and increase the risk of chronic disease in offspring. Both macronutrients and micronutrients are required for a healthy pregnancy although significantly less is understood about the role of micronutrients in the programming of chronic disease. This is despite the fact that modern calorie rich diets are often also deficient in key micronutrients. The importance of micronutrients in gestational disorders is clearly understood but how they impact long term disease in humans requires further investigation. In contrast, animal studies have demonstrated how diets high or low in specific micronutrients influence offspring physiology. Many of these studies highlight the importance of the placenta in determining disease risk. This review will explore the effects of individual vitamins, minerals and trace elements on offspring disease outcomes and discuss several key placental adaptations that are affected by multiple micronutrients. These placental adaptations include micronutrient induced dysregulation of oxidative stress, altered methyl donor availability and its impact on epigenetic mechanisms as well as endocrine dysfunction. Critical gaps in our current knowledge and the relative importance of different micronutrients at different gestational ages will also be highlighted. Finally, this review will discuss the need for further studies to characterise the micronutrient status of Australian women of reproductive age and correlate micronutrient status to placental adaptations, pregnancy complications and offspring disease. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  6. Neural Correlates of Irritability in Disruptive Mood Dysregulation and Bipolar Disorders.

    Science.gov (United States)

    Wiggins, Jillian Lee; Brotman, Melissa A; Adleman, Nancy E; Kim, Pilyoung; Oakes, Allison H; Reynolds, Richard C; Chen, Gang; Pine, Daniel S; Leibenluft, Ellen

    2016-07-01

    Bipolar disorder and disruptive mood dysregulation disorder (DMDD) are clinically and pathophysiologically distinct, yet irritability can be a clinical feature of both illnesses. The authors examine whether the neural mechanisms mediating irritability differ between bipolar disorder and DMDD, using a face emotion labeling paradigm because such labeling is deficient in both patient groups. The authors hypothesized that during face emotion labeling, irritability would be associated with dysfunctional activation in the amygdala and other temporal and prefrontal regions in both disorders, but that the nature of these associations would differ between DMDD and bipolar disorder. During functional MRI acquisition, 71 youths (25 with DMDD, 24 with bipolar disorder, and 22 healthy youths) performed a labeling task with happy, fearful, and angry faces of varying emotional intensity. Participants with DMDD and bipolar disorder showed similar levels of irritability and did not differ from each other or from healthy youths in face emotion labeling accuracy. Irritability correlated with amygdala activity across all intensities for all emotions in the DMDD group; such correlation was present in the bipolar disorder group only for fearful faces. In the ventral visual stream, associations between neural activity and irritability were found more consistently in the DMDD group than in the bipolar disorder group, especially in response to ambiguous angry faces. These results suggest diagnostic specificity in the neural correlates of irritability, a symptom of both DMDD and bipolar disorder. Such evidence of distinct neural correlates suggests the need to evaluate different approaches to treating irritability in the two disorders.

  7. An Algorithm to Automate Yeast Segmentation and Tracking

    Science.gov (United States)

    Doncic, Andreas; Eser, Umut; Atay, Oguzhan; Skotheim, Jan M.

    2013-01-01

    Our understanding of dynamic cellular processes has been greatly enhanced by rapid advances in quantitative fluorescence microscopy. Imaging single cells has emphasized the prevalence of phenomena that can be difficult to infer from population measurements, such as all-or-none cellular decisions, cell-to-cell variability, and oscillations. Examination of these phenomena requires segmenting and tracking individual cells over long periods of time. However, accurate segmentation and tracking of cells is difficult and is often the rate-limiting step in an experimental pipeline. Here, we present an algorithm that accomplishes fully automated segmentation and tracking of budding yeast cells within growing colonies. The algorithm incorporates prior information of yeast-specific traits, such as immobility and growth rate, to segment an image using a set of threshold values rather than one specific optimized threshold. Results from the entire set of thresholds are then used to perform a robust final segmentation. PMID:23520484

  8. An algorithm to automate yeast segmentation and tracking.

    Directory of Open Access Journals (Sweden)

    Andreas Doncic

    Full Text Available Our understanding of dynamic cellular processes has been greatly enhanced by rapid advances in quantitative fluorescence microscopy. Imaging single cells has emphasized the prevalence of phenomena that can be difficult to infer from population measurements, such as all-or-none cellular decisions, cell-to-cell variability, and oscillations. Examination of these phenomena requires segmenting and tracking individual cells over long periods of time. However, accurate segmentation and tracking of cells is difficult and is often the rate-limiting step in an experimental pipeline. Here, we present an algorithm that accomplishes fully automated segmentation and tracking of budding yeast cells within growing colonies. The algorithm incorporates prior information of yeast-specific traits, such as immobility and growth rate, to segment an image using a set of threshold values rather than one specific optimized threshold. Results from the entire set of thresholds are then used to perform a robust final segmentation.

  9. Differential risk for late adolescent conduct problems and mood dysregulation among children with early externalizing behavior problems.

    Science.gov (United States)

    Okado, Yuko; Bierman, Karen L

    2015-05-01

    To investigate the differential emergence of antisocial behaviors and mood dysregulation among children with externalizing problems, the present study prospectively followed 317 high-risk children with early externalizing problems from school entry (ages 5-7) to late adolescence (ages 17-19). Latent class analysis conducted on their conduct and mood symptoms in late adolescence revealed three distinct patterns of symptoms, characterized by: 1) criminal offenses, conduct disorder symptoms, and elevated anger ("conduct problems"), 2) elevated anger, dysphoric mood, and suicidal ideation ("mood dysregulation"), and 3) low levels of severe conduct and mood symptoms. A diathesis-stress model predicting the first two outcomes was tested. Elevated overt aggression at school entry uniquely predicted conduct problems in late adolescence, whereas elevated emotion dysregulation at school entry uniquely predicted mood dysregulation in late adolescence. Experiences of low parental warmth and peer rejection in middle childhood moderated the link between early emotion dysregulation and later mood dysregulation but did not moderate the link between early overt aggression and later conduct problems. Thus, among children with early externalizing behavior problems, increased risk for later antisocial behavior or mood dysfunction may be identifiable in early childhood based on levels of overt aggression and emotion dysregulation. For children with early emotion dysregulation, however, increased risk for mood dysregulation characterized by anger, dysphoric mood, and suicidality--possibly indicative of disruptive mood dysregulation disorder--emerges only in the presence of low parental warmth and/or peer rejection during middle childhood.

  10. Noise destroys feedback enhanced figure-ground segmentation but not feedforward figure-ground segmentation

    Science.gov (United States)

    Romeo, August; Arall, Marina; Supèr, Hans

    2012-01-01

    Figure-ground (FG) segmentation is the separation of visual information into background and foreground objects. In the visual cortex, FG responses are observed in the late stimulus response period, when neurons fire in tonic mode, and are accompanied by a switch in cortical state. When such a switch does not occur, FG segmentation fails. Currently, it is not known what happens in the brain on such occasions. A biologically plausible feedforward spiking neuron model was previously devised that performed FG segmentation successfully. After incorporating feedback the FG signal was enhanced, which was accompanied by a change in spiking regime. In a feedforward model neurons respond in a bursting mode whereas in the feedback model neurons fired in tonic mode. It is known that bursts can overcome noise, while tonic firing appears to be much more sensitive to noise. In the present study, we try to elucidate how the presence of noise can impair FG segmentation, and to what extent the feedforward and feedback pathways can overcome noise. We show that noise specifically destroys the feedback enhanced FG segmentation and leaves the feedforward FG segmentation largely intact. Our results predict that noise produces failure in FG perception. PMID:22934028

  11. Optimally segmented magnetic structures

    DEFF Research Database (Denmark)

    Insinga, Andrea Roberto; Bahl, Christian; Bjørk, Rasmus

    We present a semi-analytical algorithm for magnet design problems, which calculates the optimal way to subdivide a given design region into uniformly magnetized segments.The availability of powerful rare-earth magnetic materials such as Nd-Fe-B has broadened the range of applications of permanent...... is not available.We will illustrate the results for magnet design problems from different areas, such as electric motors/generators (as the example in the picture), beam focusing for particle accelerators and magnetic refrigeration devices.......We present a semi-analytical algorithm for magnet design problems, which calculates the optimal way to subdivide a given design region into uniformly magnetized segments.The availability of powerful rare-earth magnetic materials such as Nd-Fe-B has broadened the range of applications of permanent...... magnets[1][2]. However, the powerful rare-earth magnets are generally expensive, so both the scientific and industrial communities have devoted a lot of effort into developing suitable design methods. Even so, many magnet optimization algorithms either are based on heuristic approaches[3...

  12. Haematopoietic malignancies caused by dysregulation of a chromatin-binding PHD finger.

    Science.gov (United States)

    Wang, Gang G; Song, Jikui; Wang, Zhanxin; Dormann, Holger L; Casadio, Fabio; Li, Haitao; Luo, Jun-Li; Patel, Dinshaw J; Allis, C David

    2009-06-11

    Histone H3 lysine 4 methylation (H3K4me) has been proposed as a critical component in regulating gene expression, epigenetic states, and cellular identities1. The biological meaning of H3K4me is interpreted by conserved modules including plant homeodomain (PHD) fingers that recognize varied H3K4me states. The dysregulation of PHD fingers has been implicated in several human diseases, including cancers and immune or neurological disorders. Here we report that fusing an H3K4-trimethylation (H3K4me3)-binding PHD finger, such as the carboxy-terminal PHD finger of PHF23 or JARID1A (also known as KDM5A or RBBP2), to a common fusion partner nucleoporin-98 (NUP98) as identified in human leukaemias, generated potent oncoproteins that arrested haematopoietic differentiation and induced acute myeloid leukaemia in murine models. In these processes, a PHD finger that specifically recognizes H3K4me3/2 marks was essential for leukaemogenesis. Mutations in PHD fingers that abrogated H3K4me3 binding also abolished leukaemic transformation. NUP98-PHD fusion prevented the differentiation-associated removal of H3K4me3 at many loci encoding lineage-specific transcription factors (Hox(s), Gata3, Meis1, Eya1 and Pbx1), and enforced their active gene transcription in murine haematopoietic stem/progenitor cells. Mechanistically, NUP98-PHD fusions act as 'chromatin boundary factors', dominating over polycomb-mediated gene silencing to 'lock' developmentally critical loci into an active chromatin state (H3K4me3 with induced histone acetylation), a state that defined leukaemia stem cells. Collectively, our studies represent, to our knowledge, the first report that deregulation of the PHD finger, an 'effector' of specific histone modification, perturbs the epigenetic dynamics on developmentally critical loci, catastrophizes cellular fate decision-making, and even causes oncogenesis during mammalian development.

  13. Unsupervised motion-based object segmentation refined by color

    Science.gov (United States)

    Piek, Matthijs C.; Braspenning, Ralph; Varekamp, Chris

    2003-06-01

    . The presented method has no problems with bifurcations. For the pixel resolution segmentation itself we reclassify pixels such that we optimize an error norm which favour similarly coloured regions and straight edges. SEGMENTATION MEASURE To assist in the evaluation of the proposed algorithm we developed a quality metric. Because the problem does not have an exact specification, we decided to define a ground truth output which we find desirable for a given input. We define the measure for the segmentation quality as being how different the segmentation is from the ground truth. Our measure enables us to evaluate oversegmentation and undersegmentation seperately. Also, it allows us to evaluate which parts of a frame suffer from oversegmentation or undersegmentation. The proposed algorithm has been tested on several typical sequences. CONCLUSIONS In this abstract we presented a new video segmentation method which performs well in the segmentation of multiple independently moving foreground objects from each other and the background. It combines the strong points of both colour and motion segmentation in the way we expected. One of the weak points is that the segmentation method suffers from undersegmentation when adjacent objects display similar motion. In sequences with detailed backgrounds the segmentation will sometimes display noisy edges. Apart from these results, we think that some of the techniques, and in particular the K-regions technique, may be useful for other two-dimensional data segmentation problems.

  14. Segmentation of the Infant Food Market

    OpenAIRE

    Hrůzová, Daniela

    2015-01-01

    The theoretical part covers general market segmentation, namely the marketing importance of differences among consumers, the essence of market segmentation, its main conditions and the process of segmentation, which consists of four consecutive phases - defining the market, determining important criteria, uncovering segments and developing segment profiles. The segmentation criteria, segmentation approaches, methods and techniques for the process of market segmentation are also described in t...

  15. The cost of empathy: Parent-adolescent conflict predicts emotion dysregulation for highly empathic youth.

    Science.gov (United States)

    Van Lissa, Caspar J; Hawk, Skyler T; Koot, Hans M; Branje, Susan; Meeus, Wim H J

    2017-09-01

    Empathy plays a key role in maintaining close relationships and promoting prosocial conflict resolution. However, research has not addressed the potential emotional cost of adolescents' high empathy, particularly when relationships are characterized by more frequent conflict. The present 6-year longitudinal study (N = 467) investigated whether conflict with parents predicted emotion dysregulation more strongly for high-empathy adolescents than for lower-empathy adolescents. Emotion dysregulation was operationalized at both the experiential level, using mood diary data collected for 3 weeks each year, and at the dispositional level, using annual self-report measures. In line with predictions, we found that more frequent adolescent-parent conflict predicted greater day-to-day mood variability and dispositional difficulties in emotion regulation for high-empathy adolescents, but not for average- and low-empathy adolescents. Mood variability and difficulties in emotion regulation, in turn, also predicted increased conflict with parents. These links were not moderated by empathy. Moreover, our research allowed for a novel investigation of the interplay between experiential and dispositional emotion dysregulation. Day-to-day mood variability predicted increasing dispositional difficulties in emotion regulation over time, which suggests that experiential dysregulation becomes consolidated into dispositional difficulties in emotion regulation. Moderated mediation analyses revealed that, for high-empathy adolescents, conflict was a driver of this dysregulation consolidation process. Finally, emotion dysregulation played a role in overtime conflict maintenance for high-empathy adolescents. This suggests that, through emotion dysregulation, high empathy may paradoxically also contribute to maintaining negative adolescent-parent interactions. Our research indicates that high empathy comes at a cost when adolescent-parent relationships are characterized by greater negativity

  16. Segmentation of British Sign Language (BSL): Mind the gap!

    OpenAIRE

    Orfanidou, E.; McQueen, J.; Adam, R.; Morgan, G.

    2015-01-01

    This study asks how users of British Sign Language (BSL) recognize individual signs in connected sign sequences. We examined whether this is achieved through modality-specific or modality-general segmentation procedures. A modality-specific feature of signed languages is that, during continuous signing, there are salient transitions between sign locations. We used the sign-spotting task to ask if and how BSL signers use these transitions in segmentation. A total of 96 real BSL signs were prec...

  17. Superiority Of Graph-Based Visual Saliency GVS Over Other Image Segmentation Methods

    Directory of Open Access Journals (Sweden)

    Umu Lamboi

    2017-02-01

    Full Text Available Although inherently tedious the segmentation of images and the evaluation of segmented images are critical in computer vision processes. One of the main challenges in image segmentation evaluation arises from the basic conflict between generality and objectivity. For general segmentation purposes the lack of well-defined ground-truth and segmentation accuracy limits the evaluation of specific applications. Subjectivity is the most common method of evaluation of segmentation quality where segmented images are visually compared. This is daunting task however limits the scope of segmentation evaluation to a few predetermined sets of images. As an alternative supervised evaluation compares segmented images against manually-segmented or pre-processed benchmark images. Not only good evaluation methods allow for different comparisons but also for integration with target recognition systems for adaptive selection of appropriate segmentation granularity with improved recognition accuracy. Most of the current segmentation methods still lack satisfactory measures of effectiveness. Thus this study proposed a supervised framework which uses visual saliency detection to quantitatively evaluate image segmentation quality. The new benchmark evaluator uses Graph-based Visual Saliency GVS to compare boundary outputs for manually segmented images. Using the Berkeley Segmentation Database the proposed algorithm was tested against 4 other quantitative evaluation methods Probabilistic Rand Index PRI Variation of Information VOI Global Consistency Error GSE and Boundary Detection Error BDE. Based on the results the GVS approach outperformed any of the other 4 independent standard methods in terms of visual saliency detection of images.

  18. Smart markers for watershed-based cell segmentation.

    Directory of Open Access Journals (Sweden)

    Can Fahrettin Koyuncu

    Full Text Available Automated cell imaging systems facilitate fast and reliable analysis of biological events at the cellular level. In these systems, the first step is usually cell segmentation that greatly affects the success of the subsequent system steps. On the other hand, similar to other image segmentation problems, cell segmentation is an ill-posed problem that typically necessitates the use of domain-specific knowledge to obtain successful segmentations even by human subjects. The approaches that can incorporate this knowledge into their segmentation algorithms have potential to greatly improve segmentation results. In this work, we propose a new approach for the effective segmentation of live cells from phase contrast microscopy. This approach introduces a new set of "smart markers" for a marker-controlled watershed algorithm, for which the identification of its markers is critical. The proposed approach relies on using domain-specific knowledge, in the form of visual characteristics of the cells, to define the markers. We evaluate our approach on a total of 1,954 cells. The experimental results demonstrate that this approach, which uses the proposed definition of smart markers, is quite effective in identifying better markers compared to its counterparts. This will, in turn, be effective in improving the segmentation performance of a marker-controlled watershed algorithm.

  19. Smart markers for watershed-based cell segmentation.

    Science.gov (United States)

    Koyuncu, Can Fahrettin; Arslan, Salim; Durmaz, Irem; Cetin-Atalay, Rengul; Gunduz-Demir, Cigdem

    2012-01-01

    Automated cell imaging systems facilitate fast and reliable analysis of biological events at the cellular level. In these systems, the first step is usually cell segmentation that greatly affects the success of the subsequent system steps. On the other hand, similar to other image segmentation problems, cell segmentation is an ill-posed problem that typically necessitates the use of domain-specific knowledge to obtain successful segmentations even by human subjects. The approaches that can incorporate this knowledge into their segmentation algorithms have potential to greatly improve segmentation results. In this work, we propose a new approach for the effective segmentation of live cells from phase contrast microscopy. This approach introduces a new set of "smart markers" for a marker-controlled watershed algorithm, for which the identification of its markers is critical. The proposed approach relies on using domain-specific knowledge, in the form of visual characteristics of the cells, to define the markers. We evaluate our approach on a total of 1,954 cells. The experimental results demonstrate that this approach, which uses the proposed definition of smart markers, is quite effective in identifying better markers compared to its counterparts. This will, in turn, be effective in improving the segmentation performance of a marker-controlled watershed algorithm.

  20. Widespread dysregulation of MiRNAs by MYCN amplification and chromosomal imbalances in neuroblastoma: association of miRNA expression with survival.

    LENUS (Irish Health Repository)

    Bray, Isabella

    2009-01-01

    MiRNAs regulate gene expression at a post-transcriptional level and their dysregulation can play major roles in the pathogenesis of many different forms of cancer, including neuroblastoma, an often fatal paediatric cancer originating from precursor cells of the sympathetic nervous system. We have analyzed a set of neuroblastoma (n = 145) that is broadly representative of the genetic subtypes of this disease for miRNA expression (430 loci by stem-loop RT qPCR) and for DNA copy number alterations (array CGH) to assess miRNA involvement in disease pathogenesis. The tumors were stratified and then randomly split into a training set (n = 96) and a validation set (n = 49) for data analysis. Thirty-seven miRNAs were significantly over- or under-expressed in MYCN amplified tumors relative to MYCN single copy tumors, indicating a potential role for the MYCN transcription factor in either the direct or indirect dysregulation of these loci. In addition, we also determined that there was a highly significant correlation between miRNA expression levels and DNA copy number, indicating a role for large-scale genomic imbalances in the dysregulation of miRNA expression. In order to directly assess whether miRNA expression was predictive of clinical outcome, we used the Random Forest classifier to identify miRNAs that were most significantly associated with poor overall patient survival and developed a 15 miRNA signature that was predictive of overall survival with 72.7% sensitivity and 86.5% specificity in the validation set of tumors. We conclude that there is widespread dysregulation of miRNA expression in neuroblastoma tumors caused by both over-expression of the MYCN transcription factor and by large-scale chromosomal imbalances. MiRNA expression patterns are also predicative of clinical outcome, highlighting the potential for miRNA mediated diagnostics and therapeutics.

  1. Phasing multi-segment undulators

    International Nuclear Information System (INIS)

    Chavanne, J.; Elleaume, P.; Vaerenbergh, P. Van

    1996-01-01

    An important issue in the manufacture of multi-segment undulators as a source of synchrotron radiation or as a free-electron laser (FEL) is the phasing between successive segments. The state of the art is briefly reviewed, after which a novel pure permanent magnet phasing section that is passive and does not require any current is presented. The phasing section allows the introduction of a 6 mm longitudinal gap between each segment, resulting in complete mechanical independence and reduced magnetic interaction between segments. The tolerance of the longitudinal positioning of one segment with respect to the next is found to be 2.8 times lower than that of conventional phasing. The spectrum at all gaps and useful harmonics is almost unchanged when compared with a single-segment undulator of the same total length. (au) 3 refs

  2. The LOFT Ground Segment

    DEFF Research Database (Denmark)

    Bozzo, E.; Antonelli, A.; Argan, A.

    2014-01-01

    targets per orbit (~90 minutes), providing roughly ~80 GB of proprietary data per day (the proprietary period will be 12 months). The WFM continuously monitors about 1/3 of the sky at a time and provides data for about ~100 sources a day, resulting in a total of ~20 GB of additional telemetry. The LOFT...... Burst alert System additionally identifies on-board bright impulsive events (e.g., Gamma-ray Bursts, GRBs) and broadcasts the corresponding position and trigger time to the ground using a dedicated system of ~15 VHF receivers. All WFM data are planned to be made public immediately. In this contribution...... we summarize the planned organization of the LOFT ground segment (GS), as established in the mission Yellow Book 1 . We describe the expected GS contributions from ESA and the LOFT consortium. A review is provided of the planned LOFT data products and the details of the data flow, archiving...

  3. Segmented heat exchanger

    Science.gov (United States)

    Baldwin, Darryl Dean; Willi, Martin Leo; Fiveland, Scott Byron; Timmons, Kristine Ann

    2010-12-14

    A segmented heat exchanger system for transferring heat energy from an exhaust fluid to a working fluid. The heat exchanger system may include a first heat exchanger for receiving incoming working fluid and the exhaust fluid. The working fluid and exhaust fluid may travel through at least a portion of the first heat exchanger in a parallel flow configuration. In addition, the heat exchanger system may include a second heat exchanger for receiving working fluid from the first heat exchanger and exhaust fluid from a third heat exchanger. The working fluid and exhaust fluid may travel through at least a portion of the second heat exchanger in a counter flow configuration. Furthermore, the heat exchanger system may include a third heat exchanger for receiving working fluid from the second heat exchanger and exhaust fluid from the first heat exchanger. The working fluid and exhaust fluid may travel through at least a portion of the third heat exchanger in a parallel flow configuration.

  4. International EUREKA: Market Segment

    International Nuclear Information System (INIS)

    1982-03-01

    The purpose of the Market Segment of the EUREKA model is to simultaneously project uranium market prices, uranium supply and purchasing activities. The regional demands are extrinsic. However, annual forward contracting activities to meet these demands as well as inventory requirements are calculated. The annual price forecast is based on relatively short term, forward balances between available supply and desired purchases. The forecasted prices and extrapolated price trends determine decisions related to exploration and development, new production operations, and the operation of existing capacity. Purchasing and inventory requirements are also adjusted based on anticipated prices. The calculation proceeds one year at a time. Conditions calculated at the end of one year become the starting conditions for the calculation in the subsequent year

  5. Probabilistic retinal vessel segmentation

    Science.gov (United States)

    Wu, Chang-Hua; Agam, Gady

    2007-03-01

    Optic fundus assessment is widely used for diagnosing vascular and non-vascular pathology. Inspection of the retinal vasculature may reveal hypertension, diabetes, arteriosclerosis, cardiovascular disease and stroke. Due to various imaging conditions retinal images may be degraded. Consequently, the enhancement of such images and vessels in them is an important task with direct clinical applications. We propose a novel technique for vessel enhancement in retinal images that is capable of enhancing vessel junctions in addition to linear vessel segments. This is an extension of vessel filters we have previously developed for vessel enhancement in thoracic CT scans. The proposed approach is based on probabilistic models which can discern vessels and junctions. Evaluation shows the proposed filter is better than several known techniques and is comparable to the state of the art when evaluated on a standard dataset. A ridge-based vessel tracking process is applied on the enhanced image to demonstrate the effectiveness of the enhancement filter.

  6. Segmented rail linear induction motor

    Science.gov (United States)

    Cowan, Jr., Maynard; Marder, Barry M.

    1996-01-01

    A segmented rail linear induction motor has a segmented rail consisting of a plurality of nonferrous electrically conductive segments aligned along a guideway. The motor further includes a carriage including at least one pair of opposed coils fastened to the carriage for moving the carriage. A power source applies an electric current to the coils to induce currents in the conductive surfaces to repel the coils from adjacent edges of the conductive surfaces.

  7. Segmentation-DrivenTomographic Reconstruction

    DEFF Research Database (Denmark)

    Kongskov, Rasmus Dalgas

    such that the segmentation subsequently can be carried out by use of a simple segmentation method, for instance just a thresholding method. We tested the advantages of going from a two-stage reconstruction method to a one stage segmentation-driven reconstruction method for the phase contrast tomography reconstruction......The tomographic reconstruction problem is concerned with creating a model of the interior of an object from some measured data, typically projections of the object. After reconstructing an object it is often desired to segment it, either automatically or manually. For computed tomography (CT...

  8. ADVANCED CLUSTER BASED IMAGE SEGMENTATION

    Directory of Open Access Journals (Sweden)

    D. Kesavaraja

    2011-11-01

    Full Text Available This paper presents efficient and portable implementations of a useful image segmentation technique which makes use of the faster and a variant of the conventional connected components algorithm which we call parallel Components. In the Modern world majority of the doctors are need image segmentation as the service for various purposes and also they expect this system is run faster and secure. Usually Image segmentation Algorithms are not working faster. In spite of several ongoing researches in Conventional Segmentation and its Algorithms might not be able to run faster. So we propose a cluster computing environment for parallel image Segmentation to provide faster result. This paper is the real time implementation of Distributed Image Segmentation in Clustering of Nodes. We demonstrate the effectiveness and feasibility of our method on a set of Medical CT Scan Images. Our general framework is a single address space, distributed memory programming model. We use efficient techniques for distributing and coalescing data as well as efficient combinations of task and data parallelism. The image segmentation algorithm makes use of an efficient cluster process which uses a novel approach for parallel merging. Our experimental results are consistent with the theoretical analysis and practical results. It provides the faster execution time for segmentation, when compared with Conventional method. Our test data is different CT scan images from the Medical database. More efficient implementations of Image Segmentation will likely result in even faster execution times.

  9. Emotional dysregulation in those with bipolar disorder, borderline personality disorder and their comorbid expression.

    Science.gov (United States)

    Bayes, Adam; Parker, Gordon; McClure, Georgia

    2016-11-01

    Differentiation of the bipolar disorders (BP) from a borderline personality disorder (BPD) can be challenging owing to shared features, with emotional dysregulation being the likely principal one. To assess differences in emotion regulation strategies in those with BP alone, BPD alone and those comorbid for both. We interviewed participants previously receiving a BP or BPD diagnosis, studying those who met DSM criteria for one or both conditions. The sample comprised 83 with bipolar disorder, 53 with BPD and 54 comorbid for both. Analyses established linear trends, with the greatest impairment in emotion regulation strategies in the comorbid group followed by the BPD group, and with the lowest in the BP group. Specific deficits in the comorbid group included impulsivity, difficulties with goal directed behaviour, and accessing strategies. A similar linear profile was quantified for maladaptive cognitive emotion regulation strategies, weighted to catastrophizing and rumination. Adaptive emotion regulation strategies were superior in the bipolar group, without significant differences observed between the comorbid and BPD groups. Reliance on self-report measures; combined BP I and II participants limits generalisability of results to each bipolar sub-type; use of DSM diagnoses risking artefactual comorbidity; while there was an over-representation of females in all groups. Differences in emotion regulation strategies advance differentiation of those with either BP or BPD, while we identify the specificity of differing strategies to each condition and their synergic effect in those comorbid for both conditions. Study findings should assist the development and application of targeted strategies for those with either or both conditions. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

  10. EphrinB1 expression is dysregulated and promotes oncogenic signaling in medulloblastoma.

    Science.gov (United States)

    McKinney, Nicole; Yuan, Liangping; Zhang, Hongying; Liu, Jingbo; Cho, Yoon-Jae; Rushing, Elisabeth; Schniederjan, Matthew; MacDonald, Tobey J

    2015-01-01

    Eph receptors and ephrin ligands are master regulators of oncogenic signaling required for proliferation, migration, and metastasis. Yet, Eph/ephrin expression and activity in medulloblastoma (MB), the most common malignant brain tumor of childhood, remains poorly defined. We hypothesized that Eph/ephrins are differentially expressed by sonic hedgehog (SHH) and non-SHH MB and that specific members contribute to the aggressive phenotype. Affymetrix gene expression profiling of 29 childhood MB, separated into SHH (N = 11) and non-SHH (N = 18), was performed followed by protein validation of selected Eph/ephrins in another 60 MB and two MB cell lines (DAOY, D556). Functional assays were performed using MB cells overexpressing or deleted for selected ephrins. We found EPHB4 and EFNA4 almost exclusively expressed by SHH MB, whereas EPHA2, EPHA8, EFNA1 and EFNA3 are predominantly expressed by non-SHH MB. The remaining family members, except EFNB1, are ubiquitously expressed by over 70-90 % MB, irrespective of subgroup. EFNB1 is the only member differentially expressed by 28 % of SHH and non-SHH MB. Corresponding protein expression for EphB/ephrinB1 and B2 was validated in MB. Only ephrinB2 was also detected in fetal cerebellum, indicating that EphB/ephrinB1 expression is MB-specific. EphrinB1 immunopositivity localizes to tumor cells within MB with the highest proliferative index. EphrinB1 overexpression promotes EphB activation, alters F-actin distribution and morphology, decreases adhesion, and significantly promotes proliferation. Either silencing or overexpression of ephrinB1 impairs migration. These results indicate that EphrinB1 is uniquely dysregulated in MB and promotes oncogenic responses in MB cells, implicating ephrinB1 as a potential target.

  11. Emotional dysregulation and anxiety control in the psychopathological mechanism underlying drive for thinness

    Directory of Open Access Journals (Sweden)

    Francesca eFiore

    2014-04-01

    Full Text Available Emotional dysregulation is a process which consists in mitigating, intensifying or maintaining a given emotion and is the trigger for some psychological disorders. Research has shown that a anxiety control plays an important role in emotional expression and regulation and, in addition, for anorexia nervosa and, more in general, in drive for thinness. Scientific literature suggests that in anorexia nervosa there is a core of emotional dysregulation and anxiety control. The aim of this study is to explore the roles of emotional dysregulation and anxiety control as independent or third variables in a mediational regression model related to drive for thinness. 154 clinical individuals with anorexia participated in the study and all completed a set of self-report questionnaires: eating disorders inventory version 3 (EDI-3, DERS, and the anxiety control questionnaire (ACQ. The data confirmed a mediational model in which the relation between emotional dysregulation and drive for thinness is mediated by anxiety control. The current study partially supports a clinical model in which emotional dysregulation is a distal factor in eating disorders while the mediator variable anxiety control is a proximal factor in the psychopathological process underlying it.

  12. Developmental delay and emotion dysregulation: Predicting parent-child conflict across early to middle childhood

    Science.gov (United States)

    Marquis, Willa A.; Noroña, Amanda N.; Baker, Bruce L.

    2016-01-01

    Cumulative risk research has increased understanding of how multiple risk factors impact various socioemotional and interpersonal outcomes across the life span. However, little is known about risk factors for parent-child conflict early in development, where identifying predictors of change could be highly salient for intervention. Given their established association with parent-child conflict, child developmental delay (DD) and emotion dysregulation were examined as predictors of change in conflict across early to middle childhood (ages 3 to 7 years). Participants (n=211) were part of a longitudinal study examining the development of psychopathology in children with or without DD. Level of parent-child conflict was derived from naturalistic home observations, while child dysregulation was measured using an adapted CBCL-Emotion Dysregulation Index. PROCESS was used to examine the conditional interactive effects of delay status (typically developing, DD) and dysregulation on change in conflict from child ages 3 to 5 and 5 to 7 years. Across both of these timeframes, parent-child conflict increased only for families of children with both DD and high dysregulation, providing support for an interactive risk model of parent-child conflict. Findings are considered in the context of developmental transitions, and implications for intervention are discussed. PMID:28054804

  13. Understanding the connection between self-esteem and aggression: The mediating role of emotion dysregulation.

    Science.gov (United States)

    Garofalo, Carlo; Holden, Christopher J; Zeigler-Hill, Virgil; Velotti, Patrizia

    2016-01-01

    The purpose of the present study was to extend previous knowledge concerning the link between self-esteem and aggression by examining the mediating role of emotion dysregulation among offenders and community participants. A sample of 153 incarcerated violent offenders and a community sample of 197 individuals completed self-report measures of self-esteem level, emotion dysregulation, and trait aggression. Offenders reported lower levels of self-esteem than community participants, as well as greater levels of emotional nonacceptance and hostility. Bootstrapping analyses were performed to test whether emotion dysregulation mediated the association between self-esteem level and aggression. In the offender sample, mediation models were significant for three of the four aspects of trait aggression that were considered. Emotion dysregulation fully mediated the links that low self-esteem had with physical aggression, anger, and hostility. The same pattern (with the addition of full mediation for verbal aggression) was confirmed in the community sample. Our findings suggest that emotion dysregulation may play an important role in the connection between low self-esteem and aggression. Alternative models of the associations among these variables were tested and discussed. As a whole, the present results are consistent with those of other studies and suggest that it may be beneficial to include emotion regulation modules as part of prevention and treatment programs for violent offenders. © 2015 Wiley Periodicals, Inc.

  14. Dysregulated Pathway Identification of Alzheimer's Disease Based on Internal Correlation Analysis of Genes and Pathways.

    Science.gov (United States)

    Kong, Wei; Mou, Xiaoyang; Di, Benteng; Deng, Jin; Zhong, Ruxing; Wang, Shuaiqun

    2017-11-20

    Dysregulated pathway identification is an important task which can gain insight into the underlying biological processes of disease. Current pathway-identification methods focus on a set of co-expression genes and single pathways and ignore the correlation between genes and pathways. The method proposed in this study, takes into account the internal correlations not only between genes but also pathways to identifying dysregulated pathways related to Alzheimer's disease (AD), the most common form of dementia. In order to find the significantly differential genes for AD, mutual information (MI) is used to measure interdependencies between genes other than expression valves. Then, by integrating the topology information from KEGG, the significant pathways involved in the feature genes are identified. Next, the distance correlation (DC) is applied to measure the pairwise pathway crosstalks since DC has the advantage of detecting nonlinear correlations when compared to Pearson correlation. Finally, the pathway pairs with significantly different correlations between normal and AD samples are known as dysregulated pathways. The molecular biology analysis demonstrated that many dysregulated pathways related to AD pathogenesis have been discovered successfully by the internal correlation detection. Furthermore, the insights of the dysregulated pathways in the development and deterioration of AD will help to find new effective target genes and provide important theoretical guidance for drug design. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. PTSD, emotion dysregulation, and dissociative symptoms in a highly traumatized sample

    Science.gov (United States)

    Powers, Abigail; Cross, Dorthie; Fani, Negar; Bradley, Bekh

    2015-01-01

    Exposure to multiple traumas has been shown to result in many negative mental health outcomes, including posttraumatic stress disorder (PTSD). Dissociation, which involves disruptions in memory, identity, and perceptions, may be a component of PTSD, particularly among individuals who have experienced childhood trauma. Emotion regulation difficulties are also strongly associated with childhood trauma and emotion dysregulation may be a particularly important factor to consider in the development and maintenance of dissociative symptoms. The goal of the present study was to determine whether emotion dysregulation mediated the relationship between PTSD symptoms and dissociation in a sample of 154 (80% female, 97% African-American) adults recruited from a public, urban hospital. PTSD was measured using the Clinician Administered PTSD Scale, emotion dysregulation was measured using the Difficulties in Emotion Regulation Scale, and dissociation was measured using the Multiscale Dissociation Inventory. A linear regression analysis showed that both PTSD and emotion dysregulation were statistically significant predictors of dissociation even after controlling for trauma exposure. Alexithymia and an inability to use emotion regulation strategies in particular were predictive of dissociation above and beyond other predictor variables. Using bootstrapping techniques, we found that overall emotion dyregulation partially mediated the effect of PTSD symptoms on dissociative symptoms. Our results suggest that emotion dysregulation may be important in understanding the relation between PTSD and dissociative symptoms. Treatment approaches may consider a focus on training in emotional understanding and the development of adaptive regulation strategies as a way to address dissociative symptoms in PTSD patients. PMID:25573648

  16. Developmental delay and emotion dysregulation: Predicting parent-child conflict across early to middle childhood.

    Science.gov (United States)

    Marquis, Willa A; Noroña, Amanda N; Baker, Bruce L

    2017-04-01

    Cumulative risk research has increased understanding of how multiple risk factors impact various socioemotional and interpersonal outcomes across the life span. However, little is known about risk factors for parent-child conflict early in development, where identifying predictors of change could be highly salient for intervention. Given their established association with parent-child conflict, child developmental delay (DD) and emotion dysregulation were examined as predictors of change in conflict across early to middle childhood (ages 3 to 7 years). Participants (n = 211) were part of a longitudinal study examining the development of psychopathology in children with or without DD. Level of parent-child conflict was derived from naturalistic home observations, whereas child dysregulation was measured using an adapted CBCL-Emotion Dysregulation Index. PROCESS was used to examine the conditional interactive effects of delay status (typically developing, DD) and dysregulation on change in conflict from child ages 3 to 5 and 5 to 7 years. Across both of these timeframes, parent-child conflict increased only for families of children with both DD and high dysregulation, providing support for an interactive risk model of parent-child conflict. Findings are considered in the context of developmental transitions, and implications for intervention are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  17. Sexual victimization, fear of sexual powerlessness, and cognitive emotion dysregulation as barriers to sexual assertiveness in college women.

    Science.gov (United States)

    Zerubavel, Noga; Messman-Moore, Terri L

    2013-12-01

    The current study examined sexual victimization and two barriers to young women's sexual assertiveness: fear of sexual powerlessness and cognitive emotion dysregulation. College women (N = 499) responded to surveys and indicated that fear of sexual powerlessness and, to a lesser extent, cognitive emotion dysregulation were barriers to sexual assertiveness. Compared with nonvictims, sexually victimized women had greater problems with sexual assertiveness, fear of sexual powerlessness, and cognitive emotion dysregulation. Among victims, fear of sexual powerlessness and emotion dysregulation interacted to impede sexual assertiveness. Findings support targeting identified barriers in interventions to improve sexual assertiveness and reduce risk for unwanted sexual experiences and sexual victimization.

  18. Word segmentation with universal prosodic cues.

    Science.gov (United States)

    Endress, Ansgar D; Hauser, Marc D

    2010-09-01

    When listening to speech from one's native language, words seem to be well separated from one another, like beads on a string. When listening to a foreign language, in contrast, words seem almost impossible to extract, as if there was only one bead on the same string. This contrast reveals that there are language-specific cues to segmentation. The puzzle, however, is that infants must be endowed with a language-independent mechanism for segmentation, as they ultimately solve the segmentation problem for any native language. Here, we approach the acquisition problem by asking whether there are language-independent cues to segmentation that might be available to even adult learners who have already acquired a native language. We show that adult learners recognize words in connected speech when only prosodic cues to word-boundaries are given from languages unfamiliar to the participants. In both artificial and natural speech, adult English speakers, with no prior exposure to the test languages, readily recognized words in natural languages with critically different prosodic patterns, including French, Turkish and Hungarian. We suggest that, even though languages differ in their sound structures, they carry universal prosodic characteristics. Further, these language-invariant prosodic cues provide a universally accessible mechanism for finding words in connected speech. These cues may enable infants to start acquiring words in any language even before they are fine-tuned to the sound structure of their native language. Copyright © 2010. Published by Elsevier Inc.

  19. Automatic liver volume segmentation and fibrosis classification

    Science.gov (United States)

    Bal, Evgeny; Klang, Eyal; Amitai, Michal; Greenspan, Hayit

    2018-02-01

    In this work, we present an automatic method for liver segmentation and fibrosis classification in liver computed-tomography (CT) portal phase scans. The input is a full abdomen CT scan with an unknown number of slices, and the output is a liver volume segmentation mask and a fibrosis grade. A multi-stage analysis scheme is applied to each scan, including: volume segmentation, texture features extraction and SVM based classification. Data contains portal phase CT examinations from 80 patients, taken with different scanners. Each examination has a matching Fibroscan grade. The dataset was subdivided into two groups: first group contains healthy cases and mild fibrosis, second group contains moderate fibrosis, severe fibrosis and cirrhosis. Using our automated algorithm, we achieved an average dice index of 0.93 ± 0.05 for segmentation and a sensitivity of 0.92 and specificity of 0.81for classification. To the best of our knowledge, this is a first end to end automatic framework for liver fibrosis classification; an approach that, once validated, can have a great potential value in the clinic.

  20. Benchmark for license plate character segmentation

    Science.gov (United States)

    Gonçalves, Gabriel Resende; da Silva, Sirlene Pio Gomes; Menotti, David; Shwartz, William Robson

    2016-09-01

    Automatic license plate recognition (ALPR) has been the focus of many researches in the past years. In general, ALPR is divided into the following problems: detection of on-track vehicles, license plate detection, segmentation of license plate characters, and optical character recognition (OCR). Even though commercial solutions are available for controlled acquisition conditions, e.g., the entrance of a parking lot, ALPR is still an open problem when dealing with data acquired from uncontrolled environments, such as roads and highways when relying only on imaging sensors. Due to the multiple orientations and scales of the license plates captured by the camera, a very challenging task of the ALPR is the license plate character segmentation (LPCS) step, because its effectiveness is required to be (near) optimal to achieve a high recognition rate by the OCR. To tackle the LPCS problem, this work proposes a benchmark composed of a dataset designed to focus specifically on the character segmentation step of the ALPR within an evaluation protocol. Furthermore, we propose the Jaccard-centroid coefficient, an evaluation measure more suitable than the Jaccard coefficient regarding the location of the bounding box within the ground-truth annotation. The dataset is composed of 2000 Brazilian license plates consisting of 14000 alphanumeric symbols and their corresponding bounding box annotations. We also present a straightforward approach to perform LPCS efficiently. Finally, we provide an experimental evaluation for the dataset based on five LPCS approaches and demonstrate the importance of character segmentation for achieving an accurate OCR.

  1. Identification of specific antigenic epitope at N-terminal segment of enterovirus 71 (EV-71) VP1 protein and characterization of its use in recombinant form for early diagnosis of EV-71 infection.

    Science.gov (United States)

    Zhang, Jianhua; Jiang, Bingfu; Xu, Mingjie; Dai, Xing; Purdy, Michael A; Meng, Jihong

    2014-08-30

    Human enterovirus 71 (EV-71) is the main etiologic agent of hand, foot and mouth disease (HFMD). We sought to identify EV-71 specific antigens and develop serologic assays for acute-phase EV-71 infection. A series of truncated proteins within the N-terminal 100 amino acids (aa) of EV-71 VP1 was expressed in Escherichia coli. Western blot (WB) analysis showed that positions around 11-21 aa contain EV-71-specific antigenic sites, whereas positions 1-5 and 51-100 contain epitopes shared with human coxsackievirus A16 (CV-A16) and human echovirus 6 (E-6). The N-terminal truncated protein of VP1, VP₁₆₋₄₃, exhibited good stability and was recognized by anti-EV-71 specific rabbit sera. Alignment analysis showed that VP₁₆₋₄₃ is highly conserved among EV-71 strains from different genotypes but was heterologous among other enteroviruses. When the GST-VP₁₆₋₄₃ fusion protein was incorporated as antibody-capture agent in a WB assay and an ELISA for detecting anti-EV-71 IgM in human sera, sensitivities of 91.7% and 77.8% were achieved, respectively, with 100% specificity for both. The characterized EV-71 VP1 protein truncated to positions 6-43 aa has potential as an antigen for detection of anti-EV-71 IgM for early diagnosis of EV-71 infection in a WB format. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. Segmentation of medical images using explicit anatomical knowledge

    Science.gov (United States)

    Wilson, Laurie S.; Brown, Stephen; Brown, Matthew S.; Young, Jeanne; Li, Rongxin; Luo, Suhuai; Brandt, Lee

    1999-07-01

    Knowledge-based image segmentation is defined in terms of the separation of image analysis procedures and representation of knowledge. Such architecture is particularly suitable for medical image segmentation, because of the large amount of structured domain knowledge. A general methodology for the application of knowledge-based methods to medical image segmentation is described. This includes frames for knowledge representation, fuzzy logic for anatomical variations, and a strategy for determining the order of segmentation from the modal specification. This method has been applied to three separate problems, 3D thoracic CT, chest X-rays and CT angiography. The application of the same methodology to such a range of applications suggests a major role in medical imaging for segmentation methods incorporating representation of anatomical knowledge.

  3. Using machine learning and surface reconstruction to accurately differentiate different trajectories of mood and energy dysregulation in youth.

    Science.gov (United States)

    Versace, Amelia; Sharma, Vinod; Bertocci, Michele A; Bebko, Genna; Iyengar, Satish; Dwojak, Amanda; Bonar, Lisa; Perlman, Susan B; Schirda, Claudiu; Travis, Michael; Gill, Mary Kay; Diwadkar, Vaibhav A; Sunshine, Jeffrey L; Holland, Scott K; Kowatch, Robert A; Birmaher, Boris; Axelson, David; Frazier, Thomas W; Arnold, L Eugene; Fristad, Mary A; Youngstrom, Eric A; Horwitz, Sarah M; Findling, Robert L; Phillips, Mary L

    2017-01-01

    Difficulty regulating positive mood and energy is a feature that cuts across different pediatric psychiatric disorders. Yet, little is known regarding the neural mechanisms underlying different developmental trajectories of positive mood and energy regulation in youth. Recent studies indicate that machine learning techniques can help elucidate the role of neuroimaging measures in classifying individual subjects by specific symptom trajectory. Cortical thickness measures were extracted in sixty-eight anatomical regions covering the entire brain in 115 participants from the Longitudinal Assessment of Manic Symptoms (LAMS) study and 31 healthy comparison youth (12.5 y/o;-Male/Female = 15/16;-IQ = 104;-Right/Left handedness = 24/5). Using a combination of trajectories analyses, surface reconstruction, and machine learning techniques, the present study aims to identify the extent to which measures of cortical thickness can accurately distinguish youth with higher (n = 18) from those with lower (n = 34) trajectories of manic-like behaviors in a large sample of LAMS youth (n = 115; 13.6 y/o; M/F = 68/47, IQ = 100.1, R/L = 108/7). Machine learning analyses revealed that widespread cortical thickening in portions of the left dorsolateral prefrontal cortex, right inferior and middle temporal gyrus, bilateral precuneus, and bilateral paracentral gyri and cortical thinning in portions of the right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, and right parahippocampal gyrus accurately differentiate (Area Under Curve = 0.89;p = 0.03) youth with different (higher vs lower) trajectories of positive mood and energy dysregulation over a period up to 5years, as measured by the Parent General Behavior Inventory-10 Item Mania Scale. Our findings suggest that specific patterns of cortical thickness may reflect transdiagnostic neural mechanisms associated with different temporal trajectories of positive mood and energy dysregulation in youth. This approach has

  4. Using machine learning and surface reconstruction to accurately differentiate different trajectories of mood and energy dysregulation in youth.

    Directory of Open Access Journals (Sweden)

    Amelia Versace

    Full Text Available Difficulty regulating positive mood and energy is a feature that cuts across different pediatric psychiatric disorders. Yet, little is known regarding the neural mechanisms underlying different developmental trajectories of positive mood and energy regulation in youth. Recent studies indicate that machine learning techniques can help elucidate the role of neuroimaging measures in classifying individual subjects by specific symptom trajectory. Cortical thickness measures were extracted in sixty-eight anatomical regions covering the entire brain in 115 participants from the Longitudinal Assessment of Manic Symptoms (LAMS study and 31 healthy comparison youth (12.5 y/o;-Male/Female = 15/16;-IQ = 104;-Right/Left handedness = 24/5. Using a combination of trajectories analyses, surface reconstruction, and machine learning techniques, the present study aims to identify the extent to which measures of cortical thickness can accurately distinguish youth with higher (n = 18 from those with lower (n = 34 trajectories of manic-like behaviors in a large sample of LAMS youth (n = 115; 13.6 y/o; M/F = 68/47, IQ = 100.1, R/L = 108/7. Machine learning analyses revealed that widespread cortical thickening in portions of the left dorsolateral prefrontal cortex, right inferior and middle temporal gyrus, bilateral precuneus, and bilateral paracentral gyri and cortical thinning in portions of the right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, and right parahippocampal gyrus accurately differentiate (Area Under Curve = 0.89;p = 0.03 youth with different (higher vs lower trajectories of positive mood and energy dysregulation over a period up to 5years, as measured by the Parent General Behavior Inventory-10 Item Mania Scale. Our findings suggest that specific patterns of cortical thickness may reflect transdiagnostic neural mechanisms associated with different temporal trajectories of positive mood and energy dysregulation in youth. This

  5. Environmental pollutants and dysregulation of male puberty--a comparison among species.

    Science.gov (United States)

    Magnusson, Ulf; Ljungvall, Karl

    2014-04-01

    The scientific literature on altered onset of puberty predominantly involves studies on females. This paper reviews current knowledge on the role of environmental pollutants in dysregulation of male puberty in humans, laboratory rodents and farm animals. The methods used to determine the onset of puberty are well developed in humans and farm animals, and standardized across studies in humans. In laboratory rodents standardized external morphological endpoints are used. There is an increasing weight of evidence from epidemiological studies in humans, as well as from experiments in animals, indicating that environmental pollutants dysregulate puberty in males. Most data are from studies on "classical" persistent environmental pollutants. Assessing the effect of multichemical environmental pollution on dysregulation of puberty in humans is more challenging; further solid epidemiological data would likely contribute most to our understanding, especially if combined with systematically collected field-data from selected wildlife. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Exercise Training Attenuates the Dysregulated Expression of Adipokines and Oxidative Stress in White Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Takuya Sakurai

    2017-01-01

    Full Text Available Obesity-induced inflammatory changes in white adipose tissue (WAT, which caused dysregulated expression of inflammation-related adipokines involving tumor necrosis factor-α and monocyte chemoattractant protein-1, contribute to the development of insulin resistance. Moreover, current literature reports state that WAT generates reactive oxygen species (ROS, and the enhanced production of ROS in obese WAT has been closely associated with the dysregulated expression of adipokines in WAT. Therefore, the reduction in excess WAT and oxidative stress that results from obesity is thought to be one of the important strategies in preventing and improving lifestyle-related diseases. Exercise training (TR not only brings about a decrease in WAT mass but also attenuates obesity-induced dysregulated expression of the adipokines in WAT. Furthermore, some reports indicate that TR affects the generation of oxidative stress in WAT. This review outlines the impact of TR on the expression of inflammation-related adipokines and oxidative stress in WAT.

  7. Self-Concept Clarity and Emotion Dysregulation in Nonsuicidal Self-Injury.

    Science.gov (United States)

    Lear, Mary K; Pepper, Carolyn M

    2016-12-01

    Recent research has linked identity instability with engagement in nonsuicidal self-injury (NSSI; Claes, Luyckx, & Bijttebier, 2014; Claes et al., 2015). This study examined the relationship between self-concept clarity (SCC), an index of identity stability, and NSSI in a sample of 147 college students, using a cross-sectional survey design. The relationship between SCC and emotion dysregulation in NSSI severity was also examined. SCC was significantly negatively associated with NSSI engagement, as well as NSSI frequency and versatility, above negative affect or age. SCC fully accounted for the variance originally explained by emotion dysregulation in NSSI versatility. NSSI frequency was not significantly predicted by emotion regulation, but self-concept clarity reached marginal significance. These findings provide preliminary support for identity instability as a contributing factor to a relationship between emotion dysregulation and NSSI severity. Possible explanations and future research directions are discussed.

  8. Proposal of a segmentation procedure for skid resistance data

    International Nuclear Information System (INIS)

    Tejeda, S. V.; Tampier, Hernan de Solominihac; Navarro, T.E.

    2008-01-01

    Skin resistance of pavements presents a high spatial variability along a road. This pavement characteristic is directly related to wet weather accidents; therefore, it is important to identify and characterize the skid resistance of homogeneous segments along a road in order to implement proper road safety management. Several data segmentation methods have been applied to other pavement characteristics (e.g. roughness). However, no application to skin resistance data was found during the literature review for this study. Typical segmentation methods are rather too general or too specific to ensure a detailed segmentation of skid resistance data, which can be used for managing pavement performance. The main objective of this paper is to propose a procedure for segmenting skid resistance data, based on existing data segmentation methods. The procedure needs to be efficient and to fulfill road management requirements. The proposed procedure considers the Leverage method to identify outlier data, the CUSUM method to accomplish initial data segmentation and a statistical method to group consecutive segments that are statistically similar. The statistical method applies the Student's t-test of mean equities, along with analysis of variance and the Tuckey test for the multiple comparison of means. The proposed procedure was applied to a sample of skid resistance data measured with SCRIM (Side Force Coefficient Routine Investigatory Machine) on a 4.2 km section of Chilean road and was compared to conventional segmentation methods. Results showed that the proposed procedure is more efficient than the conventional segmentation procedures, achieving the minimum weighted sum of square errors (SSEp) with all the identified segments statistically different. Due to its mathematical basis, proposed procedure can be easily adapted and programmed for use in road safety management. (author)

  9. The Relationship Between Emotion Dysregulation and Impulsive Aggression in Veterans With Posttraumatic Stress Disorder Symptoms.

    Science.gov (United States)

    Miles, Shannon R; Menefee, Deleene S; Wanner, Jill; Teten Tharp, Andra; Kent, Thomas A

    2016-06-01

    While Veterans in general are no more dangerous than the civilian population, Veterans with posttraumatic stress disorder (PTSD) have stronger associations with anger and hostility and certain forms of aggression, such as intimate partner violence, than civilians with PTSD. This is alarming because up to 21% of Veterans seeking Veterans Affairs (VA) health care are diagnosed with PTSD. Emotion regulation difficulties (emotion dysregulation) are also related to increased PTSD symptom severity and may play a role in aggressive behavior. Because the predominant form of aggression in PTSD appears to be the impulsive subtype, the authors sought to clarify the relationship between PTSD, emotion dysregulation, and impulsive aggression. We examined how emotion dysregulation influenced impulsive aggression in a Veteran sample (N = 479) seeking treatment for trauma sequelae. All Veterans completed measures that assessed demographic information, emotion dysregulation, aggression frequency and subtype, and PTSD symptoms. Men generally reported more aggression than women. The emotion dysregulation, aggression, and PTSD measures were significantly correlated. Two cross-sectional mediation models showed emotion dysregulation fully accounted for the relationship between PTSD and impulsive aggression (indirect path for men: b = .07, SE = .026, bias-correct and accelerated confidence interval [BCa CI] = [0.02, 0.13]; indirect path for women: b = .08, SE = .022, BCa CI = [0.05, 0.13]). PTSD can increase negative emotions yet does not always lead to aggressive behaviors. The ability to regulate emotions may be pivotal to inhibiting aggression in those with PTSD. PTSD interventions may benefit from augmentation with emotion regulation skills training. © The Author(s) 2015.

  10. Region segmentation along image sequence

    International Nuclear Information System (INIS)

    Monchal, L.; Aubry, P.

    1995-01-01

    A method to extract regions in sequence of images is proposed. Regions are not matched from one image to the following one. The result of a region segmentation is used as an initialization to segment the following and image to track the region along the sequence. The image sequence is exploited as a spatio-temporal event. (authors). 12 refs., 8 figs

  11. Market segmentation using perceived constraints

    Science.gov (United States)

    Jinhee Jun; Gerard Kyle; Andrew Mowen

    2008-01-01

    We examined the practical utility of segmenting potential visitors to Cleveland Metroparks using their constraint profiles. Our analysis identified three segments based on their scores on the dimensions of constraints: Other priorities--visitors who scored the highest on 'other priorities' dimension; Highly Constrained--visitors who scored relatively high on...

  12. Market Segmentation: An Instructional Module.

    Science.gov (United States)

    Wright, Peter H.

    A concept-based introduction to market segmentation is provided in this instructional module for undergraduate and graduate transportation-related courses. The material can be used in many disciplines including engineering, business, marketing, and technology. The concept of market segmentation is primarily a transportation planning technique by…

  13. IFRS 8 – OPERATING SEGMENTS

    Directory of Open Access Journals (Sweden)

    BOCHIS LEONICA

    2009-05-01

    Full Text Available Segment reporting in accordance with IFRS 8 will be mandatory for annual financial statements covering periods beginning on or after 1 January 2009. The standards replaces IAS 14, Segment Reporting, from that date. The objective of IFRS 8 is to require

  14. Reduplication Facilitates Early Word Segmentation

    Science.gov (United States)

    Ota, Mitsuhiko; Skarabela, Barbora

    2018-01-01

    This study explores the possibility that early word segmentation is aided by infants' tendency to segment words with repeated syllables ("reduplication"). Twenty-four nine-month-olds were familiarized with passages containing one novel reduplicated word and one novel non-reduplicated word. Their central fixation times in response to…

  15. The Importance of Marketing Segmentation

    Science.gov (United States)

    Martin, Gillian

    2011-01-01

    The rationale behind marketing segmentation is to allow businesses to focus on their consumers' behaviors and purchasing patterns. If done effectively, marketing segmentation allows an organization to achieve its highest return on investment (ROI) in turn for its marketing and sales expenses. If an organization markets its products or services to…

  16. Essays in international market segmentation

    NARCIS (Netherlands)

    Hofstede, ter F.

    1999-01-01

    The primary objective of this thesis is to develop and validate new methodologies to improve the effectiveness of international segmentation strategies. The current status of international market segmentation research is reviewed in an introductory chapter, which provided a number of

  17. Immune System Dysregulation and Herpesvirus Reactivation Persist During Long-Duration Spaceflight

    Science.gov (United States)

    Crucian, B. E.; Mehta, S.; Stowe, R. P.; Uchakin, P.; Quiriarte, H.; Pierson, D.; Sams, C. F.

    2011-01-01

    This poster presentation reviews a study that is designed to address immune system dysregulation and the risk to crewmembers in long duration exploration class missions. This study will address these objectives: (1) Determine the status of adaptive immunity physiological stress, viral immunity, latent herpesvirus reactivation in astronauts during 6 month missions to the International Space Station; (2) determine the clinical risk related to immune dysregulation for exploration class spaceflight; and (3) determine an appropriate monitoring strategy for spaceflight-associated immune dysfunction that could be used for the evaluation of countermeasures. The study anticipates 17 subjects, and for this presentation, (midpoint study data) 10 subjects are reviewed.

  18. Dysregulation of long noncoding RNAs in mouse testes and spermatozoa after exposure to cadmium

    International Nuclear Information System (INIS)

    Gao, Fengxin; Zhang, Peng; Zhang, Hongyan; Zhang, Yunhui; Zhang, Yunwen; Hao, Qingyun; Zhang, Xiaoning

    2017-01-01

    There is increasing evidence that cadmium (Cd) exposure can cause male subfertility and even complete infertility in mammals. Long noncoding (lnc) RNAs are critical for spermatogenesis, and their dysregulation might lead to male infertility. However, whether they are involved in Cd-induced subfertility is unknown. Here we found that intraperitoneal exposure to Cd in mice led to male subfertility indicated by reductions in testicular sperm production and motility, and by abnormal morphology. Testicular and sperm RNAs were used to investigate lncRNA expression profiles by strand-specific RNA sequencing at the transcriptome level to help determine any RNA-related mechanisms in Cd-induced subfertility. The Cd-treated testes and spermatozoa exhibited aberrant expression profiles for lncRNAs and mRNAs. Of the lncRNAs, there were 139 with upregulated expression and 174 with downregulated expression in testes; in contrast, 685 were upregulated and 375 were downregulated in spermatozoa. For mRNA expression, 214 were upregulated and 226 were downregulated in testes; 272 were upregulated and 111 were downregulated in spermatozoa. Gene ontology and pathway analyses showed that the functions of differentially expressed lncRNA targets and mRNAs were closely linked with many processes involved in spermatogenesis. Additionally, many newly identified lncRNAs showed inducible expression, suggesting that they might be good candidate markers for Cd-induced male reproductive toxicity. This study provides a preliminary database for further exploring lncRNA-related mechnisms in male infertility induced by Cd. - Highlights: • LncRNA profiles were changed by Cd exposure in mouse testes and spermatozoa. • Differentially expressed lncRNA targets and mRNAs were linked with spermatogenesis. • Providing a database for exploring lncRNA-related mechnisms in male infertility. • LncRNA might be candidate markers for Cd-induced male reproductive toxicity.

  19. Humoral Dysregulation Associated with Increased Systemic Inflammation among Injection Heroin Users.

    Directory of Open Access Journals (Sweden)

    Michael S Piepenbrink

    Full Text Available Injection drug use is a growing major public health concern. Injection drug users (IDUs have a higher incidence of co-morbidities including HIV, Hepatitis, and other infections. An effective humoral response is critical for optimal homeostasis and protection from infection; however, the impact of injection heroin use on humoral immunity is poorly understood. We hypothesized that IDUs have altered B cell and antibody profiles.A comprehensive systems biology-based cross-sectional assessment of 130 peripheral blood B cell flow cytometry- and plasma- based features was performed on HIV-/Hepatitis C-, active heroin IDUs who participated in a syringe exchange program (n = 19 and healthy control subjects (n = 19. The IDU group had substantial polydrug use, with 89% reporting cocaine injection within the preceding month. IDUs exhibited a significant, 2-fold increase in total B cells compared to healthy subjects, which was associated with increased activated B cell subsets. Although plasma total IgG titers were similar between groups, IDUs had significantly higher IgG3 and IgG4, suggestive of chronic B cell activation. Total IgM was also increased in IDUs, as well as HIV Envelope-specific IgM, suggestive of increased HIV exposure. IDUs exhibited numerous features suggestive of systemic inflammation, including significantly increased plasma sCD40L, TNF-α, TGF-α, IL-8, and ceramide metabolites. Machine learning multivariate analysis distilled a set of 10 features that classified samples based on group with absolute accuracy.These results demonstrate broad alterations in the steady-state humoral profile of IDUs that are associated with increased systemic inflammation. Such dysregulation may impact the ability of IDUs to generate optimal responses to vaccination and infection, or lead to increased risk for inflammation-related co-morbidities, and should be considered when developing immune-based interventions for this growing population.

  20. Calcium dysregulation, functional calpainopathy, and endoplasmic reticulum stress in sporadic inclusion body myositis.

    Science.gov (United States)

    Amici, David R; Pinal-Fernandez, Iago; Mázala, Davi A G; Lloyd, Thomas E; Corse, Andrea M; Christopher-Stine, Lisa; Mammen, Andrew L; Chin, Eva R

    2017-03-22

    Sporadic inclusion body myositis (IBM) is the most common primary myopathy in the elderly, but its pathoetiology is still unclear. Perturbed myocellular calcium (Ca 2+ ) homeostasis can exacerbate many of the factors proposed to mediate muscle degeneration in IBM, such as mitochondrial dysfunction, protein aggregation, and endoplasmic reticulum stress. Ca 2+ dysregulation may plausibly be initiated in IBM by immune-mediated membrane damage and/or abnormally accumulating proteins, but no studies to date have investigated Ca 2+ regulation in IBM patients. We first investigated protein expression via immunoblot in muscle biopsies from IBM, dermatomyositis, and non-myositis control patients, identifying several differentially expressed Ca 2+ -regulatory proteins in IBM. Next, we investigated the Ca 2+ -signaling transcriptome by RNA-seq, finding 54 of 183 (29.5%) genes from an unbiased list differentially expressed in IBM vs. controls. Using an established statistical approach to relate genes with causal transcription networks, Ca 2+ abundance was considered a significant upstream regulator of observed whole-transcriptome changes. Post-hoc analyses of Ca 2+ -regulatory mRNA and protein data indicated a lower protein to transcript ratio in IBM vs. controls, which we hypothesized may relate to increased Ca 2+ -dependent proteolysis and decreased protein translation. Supporting this hypothesis, we observed robust (4-fold) elevation in the autolytic activation of a Ca 2+ -activated protease, calpain-1, as well as increased signaling for translational attenuation (eIF2a phosphorylation) downstream of the unfolded protein response. Finally, in IBM samples we observed mRNA and protein under-expression of calpain-3, the skeletal muscle-specific calpain, which broadly supports proper Ca 2+ homeostasis. Together, these data provide novel insight into mechanisms by which intracellular Ca 2+ regulation is perturbed in IBM and offer evidence of pathological downstream effects.

  1. Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX syndrome: a paradigm of immunodeficiency with autoimmunity

    Directory of Open Access Journals (Sweden)

    Federica eBarzaghi

    2012-07-01

    Full Text Available Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX syndrome is a rare monogenic primary immunodeficiency (PID due to mutations of FOXP3, a key transcription factor for naturally occurring (n regulatory T (Treg cells. The dysfunction of Treg cells is the main pathogenic event leading to the multi-organ autoimmunity that characterizes IPEX syndrome, a paradigm of genetically determined PID with autoimmunity. IPEX has a severe early onset and can become rapidly fatal within the first year of life regardless of the type and site of the mutation. The initial presenting symptoms are severe enteritis and/or type 1 diabetes mellitus, alone or in combination with eczema and elevated serum IgE. Other autoimmune symptoms, such as hypothyroidism, cytopenia, hepatitis, nephropathy, arthritis, and alopecia, can develop in patients who survive the initial acute phase.The current therapeutic options for IPEX patients are limited. Supportive and replacement therapies combined with pharmacological immunosuppression are required to control symptoms at onset. However, these procedures can allow only a reduction of the clinical manifestations without a permanent control of the disease. The only known effective cure for IPEX syndrome is haematopoietic stem cell transplantation, but it is always limited by the availability of a suitable donor and the lack of specific guidelines for bone marrow transplant in the context of this disease.This review aims to summarize the clinical histories and genomic mutations of the IPEX patients described in the literature to date. We will focus on the clinical and immunological features that allow differential diagnosis of IPEX syndrome and distinguish it from other PID with autoimmunity. The efficacy of the current therapies will be reviewed, and possible innovative approaches, based on the latest highlights of the pathogenesis to treat this severe primary autoimmune disease of childhood, will be discussed.

  2. Dopamine Dysregulation Syndrome and other psychiatric problems in Parkinson’s Disease: Diagnosis and Treatment

    Directory of Open Access Journals (Sweden)

    Sibel Ertan

    2011-06-01

    Full Text Available In a small number of patients with Parkinson’s disease (PD, a series of behavioral disorders included within the spectrum of impulsive-compulsive disorders develop under the dopamine replacement therapy (DRT. These behaviors are grouped into three as “impulse control disorders (ICD” characterized by rewards-seeking behaviors, “punding” characterized by aimless, ritualist stereotypical repetative behaviors, and “dopamine dysregulation syndrome (DDS” characterized by drug overuse due to chemical addiction. The prevalance of DDS in PD was reported to be around 3-4%. Patients with DDS have an urge to increase their dopaminergic doses beyond their needs for parkinsonien symptoms. DDS is reported to be more common especially in patients with an early onset of disease, high doses of DRT, previous history of or current depression, history of alcohol or substance abuse, and in those having impulsive personality constantly seeking for a change or novelty. DDS is commonly observed in association with “punding” and ICD. The pathophysiology underlying these disorders is explained by specific mechanisms in addition to DRT. Dopamine is not only responsible in the control of the movement, but also plays an important role in the modulation of brain reward systems. The potential maladaptive dysfunction of the mesolimbic dopaminergic system underlies the pathogenesis of DDS. Although the most potent trigger of DDS in PD is known as L-dopa, subcutaneous apomorphine and oral dopamine agonists could also be responsible from the development of DDS. The patients and caregivers should be informed for these behavioral disorders that might emerge under DRT, the possible risk factors should be questioned before dopaminergic therapy, and the choice of drug should be made under these concerns. In patients with DDS, fast-acting DRT formulations should be avoided. In DDS cases associated with hypomaniac or psychotic episodes, treatment should made with

  3. Dopamine Dysregulation Syndrome and other psychiatric problems in Parkinson’s Disease: Diagnosis and Treatment

    Directory of Open Access Journals (Sweden)

    Sibel Ertan

    2011-06-01

    Full Text Available In a small number of patients with Parkinson’s disease (PD, a series of behavioral disorders included within the spectrum of impulsive-compulsive disorders develop under the dopamine replacement therapy (DRT. These behaviors are grouped into three as “impulse control disorders (ICD” characterized by rewards-seeking behaviors, “punding” characterized by aimless, ritualist stereotypical repetative behaviors, and “dopamine dysregulation syndrome (DDS” characterized by drug overuse due to chemical addiction. The prevalance of DDS in PD was reported to be around 3-4%. Patients with DDS have an urge to increase their dopaminergic doses beyond their needs for parkinsonien symptoms. DDS is reported to be more common especially in patients with an early onset of disease, high doses of DRT, previous history of or current depression, history of alcohol or substance abuse, and in those having impulsive personality constantly seeking for a change or novelty. DDS is commonly observed in association with “punding” and ICD. The pathophysiology underlying these disorders is explained by specific mechanisms in addition to DRT. Dopamine is not only responsible in the control of the movement, but also plays an important role in the modulation of brain reward systems. The potential maladaptive dysfunction of the mesolimbic dopaminergic system underlies the pathogenesis of DDS. Although the most potent trigger of DDS in PD is known as L-dopa, subcutaneous apomorphine and oral dopamine agonists could also be responsible from the development of DDS. The patients and caregivers should be informed for these behavioral disorders that might emerge under DRT, the possible risk factors should be questioned before dopaminergic therapy, and the choice of drug should be made under these concerns. In patients with DDS, fast-acting DRT formulations should be avoided. In DDS cases associated with hypomaniac or psychotic episodes, treatment should made with

  4. Failure to Deliver and Translate-New Insights into RNA Dysregulation in ALS.

    Science.gov (United States)

    Coyne, Alyssa N; Zaepfel, Benjamin L; Zarnescu, Daniela C

    2017-01-01

    Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease affecting both upper and lower motor neurons. The molecular mechanisms underlying disease pathogenesis remain largely unknown. Multiple genetic loci including genes involved in proteostasis and ribostasis have been linked to ALS providing key insights into the molecular mechanisms underlying disease. In particular, the identification of the RNA binding proteins TDP-43 and fused in sarcoma (FUS) as causative factors of ALS resulted in a paradigm shift centered on the study of RNA dysregulation as a major mechanism of disease. With wild-type TDP-43 pathology being found in ~97% of ALS cases and the identification of disease causing mutations within its sequence, TDP-43 has emerged as a prominent player in ALS. More recently, studies of the newly discovered C9orf72 repeat expansion are lending further support to the notion of defects in RNA metabolism as a key factor underlying ALS. RNA binding proteins are involved in all aspects of RNA metabolism ranging from splicing, transcription, transport, storage into RNA/protein granules, and translation. How these processes are affected by disease-associated mutations is just beginning to be understood. Considerable work has gone into the identification of splicing and transcription defects resulting from mutations in RNA binding proteins associated with disease. More recently, defects in RNA transport and translation have been shown to be involved in the pathomechanism of ALS. A central hypothesis in the field is that disease causing mutations lead to the persistence of RNA/protein complexes known as stress granules. Under times of prolonged cellular stress these granules sequester specific mRNAs preventing them from translation, and are thought to evolve into pathological aggregates. Here we will review recent efforts directed at understanding how altered RNA metabolism contributes to ALS pathogenesis.

  5. Segmental vitiligo with segmental morphea: An autoimmune link?

    Directory of Open Access Journals (Sweden)

    Pravesh Yadav

    2014-01-01

    Full Text Available An 18-year old girl with segmental vitiligo involving the left side of the trunk and left upper limb with segmental morphea involving the right side of trunk and right upper limb without any deeper involvement is illustrated. There was no history of preceding drug intake, vaccination, trauma, radiation therapy, infection, or hormonal therapy. Family history of stable vitiligo in her brother and a history of type II diabetes mellitus in the father were elicited. Screening for autoimmune diseases and antithyroid antibody was negative. An autoimmune link explaining the co-occurrence has been proposed. Cutaneous mosiacism could explain the presence of both the pathologies in a segmental distribution.

  6. Segmentation and packaging reactor vessels internals

    International Nuclear Information System (INIS)

    Boucau, Joseph

    2014-01-01

    Document available in abstract form only, full text follows: With more than 25 years of experience in the development of reactor vessel internals and reactor vessel segmentation and packaging technology, Westinghouse has accumulated significant know-how in the reactor dismantling market. The primary challenges of a segmentation and packaging project are to separate the highly activated materials from the less-activated materials and package them into appropriate containers for disposal. Since disposal cost is a key factor, it is important to plan and optimize waste segmentation and packaging. The choice of the optimum cutting technology is also important for a successful project implementation and depends on some specific constraints. Detailed 3-D modeling is the basis for tooling design and provides invaluable support in determining the optimum strategy for component cutting and disposal in waste containers, taking account of the radiological and packaging constraints. The usual method is to start at the end of the process, by evaluating handling of the containers, the waste disposal requirements, what type and size of containers are available for the different disposal options, and working backwards to select a cutting method and finally the cut geometry required. The 3-D models can include intelligent data such as weight, center of gravity, curie content, etc, for each segmented piece, which is very useful when comparing various cutting, handling and packaging options. The detailed 3-D analyses and thorough characterization assessment can draw the attention to material potentially subject to clearance, either directly or after certain period of decay, to allow recycling and further disposal cost reduction. Westinghouse has developed a variety of special cutting and handling tools, support fixtures, service bridges, water filtration systems, video-monitoring systems and customized rigging, all of which are required for a successful reactor vessel internals

  7. Using Predictability for Lexical Segmentation.

    Science.gov (United States)

    Çöltekin, Çağrı

    2017-09-01

    This study investigates a strategy based on predictability of consecutive sub-lexical units in learning to segment a continuous speech stream into lexical units using computational modeling and simulations. Lexical segmentation is one of the early challenges during language acquisition, and it has been studied extensively through psycholinguistic experiments as well as computational methods. However, despite strong empirical evidence, the explicit use of predictability of basic sub-lexical units in models of segmentation is underexplored. This paper presents an incremental computational model of lexical segmentation for exploring the usefulness of predictability for lexical segmentation. We show that the predictability cue is a strong cue for segmentation. Contrary to earlier reports in the literature, the strategy yields state-of-the-art segmentation performance with an incremental computational model that uses only this particular cue in a cognitively plausible setting. The paper also reports an in-depth analysis of the model, investigating the conditions affecting the usefulness of the strategy. Copyright © 2016 Cognitive Science Society, Inc.

  8. The role of social support on emotion dysregulation and Internet addiction among Chinese adolescents: A structural equation model.

    Science.gov (United States)

    Mo, Phoenix K H; Chan, Virginia W Y; Chan, Samuel W; Lau, Joseph T F

    2018-07-01

    Internet addiction is prevalent among adolescents and is associated with various negative outcomes. Relatively few studies examined the role of emotion dysregulation and social support on Internet addiction in this population. The present examined the association between emotion dysregulation, social support, and Internet addiction among junior secondary school students in Hong Kong. The mediating role of emotion dysregulation and Internet use on the relationship between social support and Internet addiction and the gender difference in such association were also tested. A total of 862 junior secondary school students (grade 7 to 8) from 4 schools completed a cross-sectional survey. 10.9% scored above the cut-off for Internet addiction based on the Chen Internet Addiction Scale. Results from structural equation modeling revealed that social support was negatively related to emotion dysregulation and Internet usage, which in turn, were positively related to Internet addiction. Results from multi-group analysis by gender showed that the relationship between social support and emotion dysregulation, Internet usage, and Internet addiction, and those between emotion dysregulation and Internet addiction and between Internet usage and Internet addiction were stronger among female participants. Emotion dysregulation is a potential risk factor while social support is a potential protective factor for Internet addiction. The role of social support on emotion dysregulation and Internet addiction were stronger among female students. Gender-sensitive interventions on Internet Addiction for adolescents are warranted, such interventions should increase social support and improve emotion regulation. Copyright © 2018. Published by Elsevier Ltd.

  9. Dysregulation of the autonomic nervous system and its association with the presence and intensity of chronic widespread pain

    NARCIS (Netherlands)

    Barakat, A.; Vogelzangs, N.; Licht, C.M.M.; Geenen, R.; Macfarlane, G.J.; de Geus, E.J.C.; Smit, J.H.; Penninx, B.W.J.H.; Dekker, J.

    2012-01-01

    Objective To test the hypotheses that dysregulation of the autonomic nervous system (ANS) is associated with the presence of chronic widespread pain (CWP), and that dysregulation of the ANS is associated with higher pain intensity in CWP. Methods Cross-sectional data were obtained from 1,574

  10. Dysregulation of the Autonomic Nervous System and Its Association With the Presence and Intensity of Chronic Widespread Pain

    NARCIS (Netherlands)

    Barakat, Ansam; Vogelzangs, Nicole; Licht, Carmilla M. M.; Geenen, Rinie; Macfarlane, Gary J.; de Geus, Eco J. C.; Smit, Johannes H.; Penninx, Brenda W. J. H.; Dekker, Joost

    Objective. To test the hypotheses that dysregulation of the autonomic nervous system (ANS) is associated with the presence of chronic widespread pain (CWP), and that dysregulation of the ANS is associated with higher pain intensity in CWP. Methods. Cross-sectional data were obtained from 1,574

  11. Integrating Dialectical Behavior Therapy and Cognitive-Behavioral Couple Therapy: A Couples Skills Group for Emotion Dysregulation

    Science.gov (United States)

    Kirby, Jennifer S.; Baucom, Donald H.

    2007-01-01

    Given the reciprocal influences of emotion dysregulation and relationship functioning, it is important to target such emotional difficulties within an interpersonal context. Treating emotion dysregulation within intimate relationships can offer valuable opportunities for both emotional and relationship difficulties to be addressed. This paper…

  12. Markers of impaired motor and cognitive volition in Parkinson's disease: Correlates of dopamine dysregulation syndrome, impulse control disorder, and dyskinesias.

    Science.gov (United States)

    Hinkle, Jared T; Perepezko, Kate; Rosenthal, Liana S; Mills, Kelly A; Pantelyat, Alexander; Mari, Zoltan; Tochen, Laura; Bang, Jee Yun; Gudavalli, Medha; Yoritomo, Nadine; Butala, Ankur; Bakker, Catherine C; Johnson, Vanessa; Moukheiber, Emile; Dawson, Ted M; Pontone, Gregory M

    2018-02-01

    Dopaminergic therapy in Parkinson's disease (PD) can be associated with both motoric (e.g., dyskinesias) and neuropsychiatric adverse effects. Examples of the latter include Dopamine Dysregulation Syndrome (DDS) and impulse control disorder (ICD), which are separate but related behavioral/psychiatric complications of treatment in PD. Dysregulation of volition characterizes both dyskinesias and DDS/ICD; thus, we analyzed potential disease-related correlates in a large PD cohort. We analyzed cross-sectional data from 654 participants collected through the NINDS Parkinson's Disease Biomarkers Program. DDS/ICD symptoms and dyskinesias were assessed using the Movement Disorders Society (revised) Unified Parkinson's Disease Rating Scale. Potential associated variables were selected from PD-validated or PD-specific scales of neuropsychiatric or motoric status. Multivariable models with DDS/ICD or dyskinesia presence outcomes were produced with backward stepwise regression to identify factors independently associated with DDS/ICD and/or dyskinesias. Fifty-three (8.1%) participants endorsed DDS and/or ICD symptoms and 150 (22.9%) were dyskinetic. In multivariable analysis, psychosis was independently associated with both dyskinesias (p = 0.006) and DDS/ICD (p < 0.001). Unpredictable motor fluctuations (p = 0.026) and depression (p = 0.023) were also associated with DDS/ICD; female sex (p = 0.025), low tremor score (p = 0.001) and high akinesia-rigidity score (p < 0.001) were associated with dyskinesias. Our findings suggest that psychosis may be an important marker of impaired volition across motor and cognitive domains. Unpredictable motor fluctuations, psychosis, and depression may together comprise a phenotypic profile of patients at increased risk for DDS/ICD. Similarly, dyskinetic PD patients should be closely monitored for psychotic symptoms and treated appropriately. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. MARKET SEGMENTATION PRACTICES OF RETAIL CROP INPUT FIRMS

    OpenAIRE

    Jay Akridge; Mike Boehlje; Allan Gray; Aaron Reimer

    2007-01-01

    While market segmentation and the associated idea of target marketing are not new, there are questions about how the strategy of market segmentation and target marketing is being used in retail agribusiness firms. Previous research has demonstrated that distinct groups of farmers/customers exist (Alexander). However, retail crop input firms tend to be of modest size and are geographically bound. Both lack of resources and confinement to a specific geographic market present challenges for succ...

  14. Supply chain segmentation in the sporting goods industry

    OpenAIRE

    Roscoe, S.; Baker, P.

    2014-01-01

    The purpose of this paper is to explore the factors that influence supply chain segmentation when selling to consumers through retail chains. The initial research is based on a review of supply chain segmentation literature and the application of relevant parameters to a specific case study, comprising two major brands in the sporting goods industry. The empirical research itself comprises semi-structured interviews, covering demand planning, sales, marketing and supply chain managers, suppor...

  15. Tissues segmentation based on multi spectral medical images

    Science.gov (United States)

    Li, Ya; Wang, Ying

    2017-11-01

    Each band image contains the most obvious tissue feature according to the optical characteristics of different tissues in different specific bands for multispectral medical images. In this paper, the tissues were segmented by their spectral information at each multispectral medical images. Four Local Binary Patter descriptors were constructed to extract blood vessels based on the gray difference between the blood vessels and their neighbors. The segmented tissue in each band image was merged to a clear image.

  16. Cyanide sulphur transferase from the gut and body segments of ...

    African Journals Online (AJOL)

    Our results show total rhodanese activities of 1434.50 RU and 2274.28 RU and specific activities of 108.01 RUmg-1 and 83.1901 RUmg-1 in the gut and body segments of H. africanus respectively. The optimum temperature of 25 °C and optimum pH of 10.5 were obtained for both the gut and body segments enzymes.

  17. The Hierarchy of Segment Reports

    Directory of Open Access Journals (Sweden)

    Danilo Dorović

    2015-05-01

    Full Text Available The article presents an attempt to find the connection between reports created for managers responsible for different business segments. With this purpose, the hierarchy of the business reporting segments is proposed. This can lead to better understanding of the expenses under common responsibility of more than one manager since these expenses should be in more than one report. The structure of cost defined per business segment hierarchy with the aim of new, unusual but relevant cost structure for management can be established. Both could potentially bring new information benefits for management in the context of profit reporting.

  18. Segmental dilatation of the ileum

    Directory of Open Access Journals (Sweden)

    Tune-Yie Shih

    2017-01-01

    Full Text Available A 2-year-old boy was sent to the emergency department with the chief problem of abdominal pain for 1 day. He was just discharged from the pediatric ward with the diagnosis of mycoplasmal pneumonia and paralytic ileus. After initial examinations and radiographic investigations, midgut volvulus was impressed. An emergency laparotomy was performed. Segmental dilatation of the ileum with volvulus was found. The operative procedure was resection of the dilated ileal segment with anastomosis. The postoperative recovery was uneventful. The unique abnormality of gastrointestinal tract – segmental dilatation of the ileum, is described in details and the literature is reviewed.

  19. A segment of the apospory-specific genomic region is highly microsyntenic not only between the apomicts Pennisetum squamulatum and buffelgrass, but also with a rice chromosome 11 centromeric-proximal genomic region.

    Science.gov (United States)

    Gualtieri, Gustavo; Conner, Joann A; Morishige, Daryl T; Moore, L David; Mullet, John E; Ozias-Akins, Peggy

    2006-03-01

    Bacterial artificial chromosome (BAC) clones from apomicts Pennisetum squamulatum and buffelgrass (Cenchrus ciliaris), isolated with the apospory-specific genomic region (ASGR) marker ugt197, were assembled into contigs that were extended by chromosome walking. Gene-like sequences from contigs were identified by shotgun sequencing and BLAST searches, and used to isolate orthologous rice contigs. Additional gene-like sequences in the apomicts' contigs were identified by bioinformatics using fully sequenced BACs from orthologous rice contigs as templates, as well as by interspecies, whole-contig cross-hybridizations. Hierarchical contig orthology was rapidly assessed by constructing detailed long-range contig molecular maps showing the distribution of gene-like sequences and markers, and searching for microsyntenic patterns of sequence identity and spatial distribution within and across species contigs. We found microsynteny between P. squamulatum and buffelgrass contigs. Importantly, this approach also enabled us to isolate from within the rice (Oryza sativa) genome contig Rice A, which shows the highest microsynteny and is most orthologous to the ugt197-containing C1C buffelgrass contig. Contig Rice A belongs to the rice genome database contig 77 (according to the current September 12, 2003, rice fingerprint contig build) that maps proximal to the chromosome 11 centromere, a feature that interestingly correlates with the mapping of ASGR-linked BACs proximal to the centromere or centromere-like sequences. Thus, relatedness between these two orthologous contigs is supported both by their molecular microstructure and by their centromeric-proximal location. Our discoveries promote the use of a microsynteny-based positional-cloning approach using the rice genome as a template to aid in constructing the ASGR toward the isolation of genes underlying apospory.

  20. A Segment of the Apospory-Specific Genomic Region Is Highly Microsyntenic Not Only between the Apomicts Pennisetum squamulatum and Buffelgrass, But Also with a Rice Chromosome 11 Centromeric-Proximal Genomic Region1[W

    Science.gov (United States)

    Gualtieri, Gustavo; Conner, Joann A.; Morishige, Daryl T.; Moore, L. David; Mullet, John E.; Ozias-Akins, Peggy

    2006-01-01

    Bacterial artificial chromosome (BAC) clones from apomicts Pennisetum squamulatum and buffelgrass (Cenchrus ciliaris), isolated with the apospory-specific genomic region (ASGR) marker ugt197, were assembled into contigs that were extended by chromosome walking. Gene-like sequences from contigs were identified by shotgun sequencing and BLAST searches, and used to isolate orthologous rice contigs. Additional gene-like sequences in the apomicts' contigs were identified by bioinformatics using fully sequenced BACs from orthologous rice contigs as templates, as well as by interspecies, whole-contig cross-hybridizations. Hierarchical contig orthology was rapidly assessed by constructing detailed long-range contig molecular maps showing the distribution of gene-like sequences and markers, and searching for microsyntenic patterns of sequence identity and spatial distribution within and across species contigs. We found microsynteny between P. squamulatum and buffelgrass contigs. Importantly, this approach also enabled us to isolate from within the rice (Oryza sativa) genome contig Rice A, which shows the highest microsynteny and is most orthologous to the ugt197-containing C1C buffelgrass contig. Contig Rice A belongs to the rice genome database contig 77 (according to the current September 12, 2003, rice fingerprint contig build) that maps proximal to the chromosome 11 centromere, a feature that interestingly correlates with the mapping of ASGR-linked BACs proximal to the centromere or centromere-like sequences. Thus, relatedness between these two orthologous contigs is supported both by their molecular microstructure and by their centromeric-proximal location. Our discoveries promote the use of a microsynteny-based positional-cloning approach using the rice genome as a template to aid in constructing the ASGR toward the isolation of genes underlying apospory. PMID:16415213

  1. Dynamic ligand modulation of EPO receptor pools, and dysregulation by polycythemia-associated EPOR alleles.

    Directory of Open Access Journals (Sweden)

    Seema Singh

    which mutated EPOR-T polycythemia alleles dysregulate the erythron. Notably, specific new tools also are characterized for studies of EPOR expression, activation, action and metabolism.

  2. Dynamic Ligand Modulation of EPO Receptor Pools, and Dysregulation by Polycythemia-Associated EPOR Alleles

    Science.gov (United States)

    Singh, Seema; Verma, Rakesh; Pradeep, Anamika; Leu, Karen; Mortensen, R. Bruce; Young, Peter R.; Oyasu, Miho; Schatz, Peter J.; Green, Jennifer M.; Wojchowski, Don M.

    2012-01-01

    mutated EPOR-T polycythemia alleles dysregulate the erythron. Notably, specific new tools also are characterized for studies of EPOR expression, activation, action and metabolism. PMID:22253704

  3. Accounting for segment correlations in segmented gamma-ray scans

    International Nuclear Information System (INIS)

    Sheppard, G.A.; Prettyman, T.H.; Piquette, E.C.

    1994-01-01

    In a typical segmented gamma-ray scanner (SGS), the detector's field of view is collimated so that a complete horizontal slice or segment of the desired thickness is visible. Ordinarily, the collimator is not deep enough to exclude gamma rays emitted from sample volumes above and below the segment aligned with the collimator. This can lead to assay biases, particularly for certain radioactive-material distributions. Another consequence of the collimator's low aspect ratio is that segment assays at the top and bottom of the sample are biased low because the detector's field of view is not filled. This effect is ordinarily countered by placing the sample on a low-Z pedestal and scanning one or more segment thicknesses below and above the sample. This takes extra time, however, We have investigated a number of techniques that both account for correlated segments and correct for end effects in SGS assays. Also, we have developed an algorithm that facilitates estimates of assay precision. Six calculation methods have been compared by evaluating the results of thousands of simulated, assays for three types of gamma-ray source distribution and ten masses. We will report on these computational studies and their experimental verification

  4. Family enmeshment, adolescent emotional dysregulation, and the moderating role of gender.

    Science.gov (United States)

    Kivisto, Katherine Little; Welsh, Deborah P; Darling, Nancy; Culpepper, Christi L

    2015-08-01

    Enmeshment plays a key role in many families' dysfunctional interactions and may be especially detrimental for adolescents. Sixty-four adolescents completed ratings of family enmeshment, perceived distress tolerance, an interpersonal challenge task, and mood ratings before and immediately after the task. Before and during the challenge task, adolescents' respiratory sinus arrhythmia (an indicator of cardiac vagal tone) was recorded. Associations were tested between adolescents' perceptions of family enmeshment and 3 aspects of adolescent emotional dysregulation. Adolescents who perceived higher family enmeshment also demonstrated greater emotional dysregulation in several domains: negative global appraisals of distress tolerance, stronger increase in subjective negative mood from baseline to postchallenge, lower baseline vagal tone, and vagal augmentation during the challenge task. Gender differences also emerged, such that girls reported more negative distress appraisals overall and enmeshed boys showed greater emotional dysregulation across analyses. Findings are discussed in terms of how clinicians may dynamically assess and treat enmeshment and emotional dysregulation in families with male and female adolescents. (c) 2015 APA, all rights reserved).

  5. Emotion Dysregulation and Anxiety in Adults with ASD: Does Social Motivation Play a Role?

    Science.gov (United States)

    Swain, Deanna; Scarpa, Angela; White, Susan; Laugeson, Elizabeth

    2015-01-01

    Young adults with ASD and no intellectual impairment are more likely to exhibit clinical levels of anxiety than typically developing peers (DSM-5, American Psychiatric Association, 2013). This study tests a mechanistic model in which anxiety culminates via emotion dysregulation and social motivation. Adults with ASD (49 males, 20 females)…

  6. Emotion regulation and aggression : The incremental contribution of alexithymia, impulsivity, and emotion dysregulation facets

    NARCIS (Netherlands)

    Garofalo, C.; Velotti, Patrizia; Zavattini, Giulio Cesare

    2018-01-01

    Objective: Prior research has long emphasized the role of alexithymia and impulsivity to explain aggressive tendencies. Recently, a growing body of research seems to support the relevance of the broader construct of emotion dysregulation to understand aggression. The present study was the first to

  7. In Search of HPA Axis Dysregulation in Child and Adolescent Depression

    Science.gov (United States)

    Guerry, John D.; Hastings, Paul D.

    2011-01-01

    Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in adults with major depressive disorder is among the most consistent and robust biological findings in psychiatry. Given the importance of the adolescent transition to the development and recurrence of depressive phenomena over the lifespan, it is important to have an integrative…

  8. Investigating multiple dysregulated pathways in rheumatoid arthritis based on pathway interaction network.

    Science.gov (United States)

    Song, Xian-Dong; Song, Xian-Xu; Liu, Gui-Bo; Ren, Chun-Hui; Sun, Yuan-Bo; Liu, Ke-Xin; Liu, Bo; Liang, Shuang; Zhu, Zhu

    2018-03-01

    The traditional methods of identifying biomarkers in rheumatoid arthritis (RA) have focussed on the differentially expressed pathways or individual pathways, which however, neglect the interactions between pathways. To better understand the pathogenesis of RA, we aimed to identify dysregulated pathway sets using a pathway interaction network (PIN), which considered interactions among pathways. Firstly, RA-related gene expression profile data, protein-protein interactions (PPI) data and pathway data were taken up from the corresponding databases. Secondly, principal component analysis method was used to calculate the pathway activity of each of the pathway, and then a seed pathway was identified using data gleaned from the pathway activity. A PIN was then constructed based on the gene expression profile, pathway data, and PPI information. Finally, the dysregulated pathways were extracted from the PIN based on the seed pathway using the method of support vector machines and an area under the curve (AUC) index. The PIN comprised of a total of 854 pathways and 1064 pathway interactions. The greatest change in the activity score between RA and control samples was observed in the pathway of epigenetic regulation of gene expression, which was extracted and regarded as the seed pathway. Starting with this seed pathway, one maximum pathway set containing 10 dysregulated pathways was extracted from the PIN, having an AUC of 0.8249, and the result indicated that this pathway set could distinguish RA from the controls. These 10 dysregulated pathways might be potential biomarkers for RA diagnosis and treatment in the future.

  9. The Impact of Alexithymia on Emotion Dysregulation in Anorexia Nervosa and Bulimia Nervosa over Time.

    Science.gov (United States)

    Brown, Tiffany A; Avery, Jade C; Jones, Michelle D; Anderson, Leslie K; Wierenga, Christina E; Kaye, Walter H

    2018-03-01

    Research supports that anorexia nervosa-restricting subtype (AN-R) and bulimia nervosa (BN) are associated with emotion regulation difficulties and alexithymia. However, the impact of diagnosis on the relationship between these constructs is less well understood. The purpose of the present study was to examine whether eating disorder diagnosis moderated the association between admission alexithymia and emotion regulation through discharge. Adult patients with AN-R (n = 54) and BN (n = 60) completed assessments at treatment admission and discharge from a partial hospital program. Eating disorder diagnosis moderated the association between admission alexithymia levels and change in global emotion dysregulation, impulse control difficulties and access to emotion regulation strategies. At higher levels of admission alexithymia, there were no differences between AN-R and BN on emotion dysregulation, whereas at lower levels of alexithymia, AN-R patients demonstrated lower levels of emotion dysregulation. Results imply that difficulties with alexithymia appear to have a greater impact on emotion dysregulation for AN-R patients. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

  10. Just Breathe: The Effects of Emotional Dysregulation and Test Anxiety on GPA

    Science.gov (United States)

    Hartman, Samantha D.; Wasieleski, David T.; Whatley, Mark A.

    2017-01-01

    College is considered to be one of the most evaluative and stressful times during a student's academic career. A student's inability to regulate emotions may be correlated with an increased level of test anxiety. Previous research has indicated significant relationships between emotional dysregulation and generalized anxiety disorders (e.g.,…

  11. Pediatric Bipolar Disorder versus Severe Mood Dysregulation: Risk for Manic Episodes on Follow-Up

    Science.gov (United States)

    Stringaris, Argyris; Baroni, Argelinda; Haimm, Caroline; Brotman, Melissa; Lowe, Catherine H.; Myers, Frances; Rustgi, Eileen; Wheeler, Wanda; Kayser, Reilly; Towbin, Kenneth; Leibenluft, Ellen

    2010-01-01

    Objective: An important question in pediatric bipolar research is whether marked nonepisodic irritability is a manifestation of bipolar disorder in youth. This study tests the hypothesis that youth with severe mood dysregulation (SMD), a category created for the purpose of studying children presenting with severe nonepisodic irritability, will be…

  12. Differentiating Bipolar Disorder--Not Otherwise Specified and Severe Mood Dysregulation

    Science.gov (United States)

    Towbin, Kenneth; Axelson, David; Leibenluft, Ellen; Birmaher, Boris

    2013-01-01

    Objective: Bipolar disorder--not otherwise specified (BP-NOS) and severe mood dysregulation (SMD) are severe mood disorders that were defined to address questions about the diagnosis of bipolar disorder (BD) in youth. SMD and BP-NOS are distinct phenotypes that differ in clinical presentation and longitudinal course. The purpose of this review is…

  13. Neural Correlates of Reversal Learning in Severe Mood Dysregulation and Pediatric Bipolar Disorder

    Science.gov (United States)

    Adleman, Nancy E.; Kayser, Reilly; Dickstein, Daniel; Blair, R. James R.; Pine, Daniel; Leibenluft, Ellen

    2011-01-01

    Objective: Outcome and family history data differentiate children with severe mood dysregulation (SMD), a syndrome characterized by chronic irritability, from children with "classic" episodic bipolar disorder (BD). Nevertheless, the presence of cognitive inflexibility in SMD and BD highlights the need to delineate neurophysiologic similarities and…

  14. Severe Affective and Behavioural Dysregulation Is Associated with Significant Psychosocial Adversity and Impairment

    Science.gov (United States)

    Jucksch, Viola; Salbach-Andrae, Harriet; Lenz, Klaus; Goth, Kirstin; Dopfner, Manfred; Poustka, Fritz; Freitag, Christine M.; Lehmkuhl, Gerd; Lehmkuhl, Ulrike; Holtmann, Martin

    2011-01-01

    Background: Recently, a highly heritable behavioral phenotype of simultaneous deviance on the Anxious/Depressed, Attention Problems, and Aggressive Behavior syndrome scales has been identified on the Child Behavior Checklist (CBCL-Dysregulation Profile, CBCL-DP). This study aims to investigate psychosocial adversity and impairment of the CBCL-DP.…

  15. Dysregulation of the mitosis-meiosis switch in testicular carcinoma in situ

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Nielsen, John E; Almstrup, Kristian

    2013-01-01

    , except in spermatocytic seminoma (not derived from CIS). In conclusion, this study indicates that meiosis signalling is dysregulated in CIS cells and that a key regulator of the mitosis-meiosis switch, DMRT1, is expressed in 'early-stage' CIS cells but is down-regulated with further invasive...

  16. A novel statistical approach shows evidence for multi-system physiological dysregulation during aging.

    Science.gov (United States)

    Cohen, Alan A; Milot, Emmanuel; Yong, Jian; Seplaki, Christopher L; Fülöp, Tamàs; Bandeen-Roche, Karen; Fried, Linda P

    2013-03-01

    Previous studies have identified many biomarkers that are associated with aging and related outcomes, but the relevance of these markers for underlying processes and their relationship to hypothesized systemic dysregulation is not clear. We address this gap by presenting a novel method for measuring dysregulation via the joint distribution of multiple biomarkers and assessing associations of dysregulation with age and mortality. Using longitudinal data from the Women's Health and Aging Study, we selected a 14-marker subset from 63 blood measures: those that diverged from the baseline population mean with age. For the 14 markers and all combinatorial sub-subsets we calculated a multivariate distance called the Mahalanobis distance (MHBD) for all observations, indicating how "strange" each individual's biomarker profile was relative to the baseline population mean. In most models, MHBD correlated positively with age, MHBD increased within individuals over time, and higher MHBD predicted higher risk of subsequent mortality. Predictive power increased as more variables were incorporated into the calculation of MHBD. Biomarkers from multiple systems were implicated. These results support hypotheses of simultaneous dysregulation in multiple systems and confirm the need for longitudinal, multivariate approaches to understanding biomarkers in aging. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Parental Interpersonal Sensitivity and Youth Social Problems: A Mediational Role for Child Emotion Dysregulation

    Science.gov (United States)

    Suveg, Cynthia; Jacob, Marni L.; Payne, Mary

    2010-01-01

    We examined the relations between parental interpersonal sensitivity and youth social problems and explored the mediational role of child emotion dysregulation. Mothers (N = 42; M age = 39.38) and fathers (N = 41; M age = 39.38) of youth aged 7-12 (N = 42; M age = 9.12) completed measures of their own interpersonal sensitivity and reported on…

  18. Aldosterone dysregulation with aging predicts renal vascular function and cardiovascular risk.

    Science.gov (United States)

    Brown, Jenifer M; Underwood, Patricia C; Ferri, Claudio; Hopkins, Paul N; Williams, Gordon H; Adler, Gail K; Vaidya, Anand

    2014-06-01

    Aging and abnormal aldosterone regulation are both associated with vascular disease. We hypothesized that aldosterone dysregulation influences the age-related risk of renal vascular and cardiovascular disease. We conducted an analysis of 562 subjects who underwent detailed investigations under conditions of liberal and restricted dietary sodium intake (1124 visits) in the General Clinical Research Center. Aldosterone regulation was characterized by the ratio of maximal suppression to stimulation (supine serum aldosterone on a liberal sodium diet divided by the same measure on a restricted sodium diet). We previously demonstrated that higher levels of this Sodium-modulated Aldosterone Suppression-Stimulation Index (SASSI) indicate greater aldosterone dysregulation. Renal plasma flow (RPF) was determined via p-aminohippurate clearance to assess basal renal hemodynamics and the renal vascular responses to dietary sodium manipulation and angiotensin II infusion. Cardiovascular risk was calculated using the Framingham Risk Score. In univariate linear regression, older age (β=-4.60; Page and SASSI, where the inverse relationship between SASSI and RPF was most apparent with older age (Page may interact to mediate renal vascular disease. Our findings suggest that the combination of aldosterone dysregulation and renal vascular dysfunction could additively increase the risk of future cardiovascular outcomes; therefore, aldosterone dysregulation may represent a modifiable mechanism of age-related vascular disease.

  19. Understanding the connection between self-esteem and aggression : The mediating role of emotion dysregulation

    NARCIS (Netherlands)

    Garofalo, C.; Holden, C.J.; Zeigler-Hill, V.; Velotti, P.

    2016-01-01

    The purpose of the present study was to extend previous knowledge concerning the link between self-esteem and aggression by examining the mediating role of emotion dysregulation among offenders and community participants. A sample of 153 incarcerated violent offenders and a community sample of 197

  20. Initial Development of a Measure of Emotional Dysregulation for Individuals with Cluster B Personality Disorders

    Science.gov (United States)

    Newhill, Christina E.; Mulvey, Edward P.; Pilkonis, Paul A.

    2004-01-01

    Individuals with DSM-IV Cluster B personality disorders are at particular risk of violence toward self or others. Emotional dysregulation is likely to be a factor in such incidents and is a central issue addressed in therapies with personality-disordered individuals. This article reports findings from a study that developed an original 18-item…

  1. Adult Outcomes of Childhood Dysregulation: A 14-Year Follow-up Study

    Science.gov (United States)

    Althoff, Robert R.; Verhulst, Frank C.; Rettew, David C.; Hudziak, James J.; van der Ende, Jan

    2010-01-01

    Objective: Using a general population sample, the adult outcomes of children who presented with severe problems with self-regulation defined as being concurrently rated highly on attention problems, aggressive behavior, and anxious-depression on the Child Behavior Checklist-Dysregulation Profile (CBCL-DP) were examined. Method: Two thousand…

  2. The Impact of Attachment Security and Emotion Dysregulation on Anxiety in Children and Adolescents

    Science.gov (United States)

    Bender, Patrick K.; Sømhovd, Mikael; Pons, Francisco; Reinholdt-Dunne, Marie L.; Esbjørn, Barbara H.

    2015-01-01

    Theoretical views and empirical findings suggest interrelations among attachment security, emotion dysregulation and anxiety in childhood and adolescence. However, the associations among the three constructs have rarely been investigated in children, and no study has yet addressed these associations in adolescence. The aim of the present study was…

  3. Pathway Interaction Network Analysis Identifies Dysregulated Pathways in Human Monocytes Infected by Listeria monocytogenes

    Directory of Open Access Journals (Sweden)

    Wufeng Fan

    2017-01-01

    Full Text Available In our study, we aimed to extract dysregulated pathways in human monocytes infected by Listeria monocytogenes (LM based on pathway interaction network (PIN which presented the functional dependency between pathways. After genes were aligned to the pathways, principal component analysis (PCA was used to calculate the pathway activity for each pathway, followed by detecting seed pathway. A PIN was constructed based on gene expression profile, protein-protein interactions (PPIs, and cellular pathways. Identifying dysregulated pathways from the PIN was performed relying on seed pathway and classification accuracy. To evaluate whether the PIN method was feasible or not, we compared the introduced method with standard network centrality measures. The pathway of RNA polymerase II pretranscription events was selected as the seed pathway. Taking this seed pathway as start, one pathway set (9 dysregulated pathways with AUC score of 1.00 was identified. Among the 5 hub pathways obtained using standard network centrality measures, 4 pathways were the common ones between the two methods. RNA polymerase II transcription and DNA replication owned a higher number of pathway genes and DEGs. These dysregulated pathways work together to influence the progression of LM infection, and they will be available as biomarkers to diagnose LM infection.

  4. Transmission of Neglect in Substance Abuse Families: The Role of Child Dysregulation and Parental SUD.

    Science.gov (United States)

    Dunn, Marija G.; Mezzich, Ada; Janiszewski, Susan; Kirisci, Levent; Tarter, Ralph E.

    2001-01-01

    Paternal and maternal models of transmission of child neglect were tested separately in offspring of men with a substance use disorder (SUD). Child dysregulation was independently related to neglect severity. SUD in the mother directly correlated with severity of neglectful parenting. (Contains 51 references and 2 tables.) (GCP)

  5. Cortisol Predicts Behavioral Dysregulation and Length of Stay among Children Admitted for Psychiatric Inpatient Treatment

    Science.gov (United States)

    Luebbe, Aaron M.; Elledge, L. Christian; Kiel, Elizabeth J.; Stoppelbein, Laura

    2012-01-01

    Individual differences in behavioral regulation system (BRS) and stress response system (SRS) functioning may reflect greater biological sensitivity to context. The current study tested whether children's cortisol, a measure of the SRS, was related to observed dysregulated behavior, an indicator of the BRS, in a sample of children admitted for…

  6. A Novel Group Therapy for Children with ADHD and Severe Mood Dysregulation

    Science.gov (United States)

    Waxmonsky, James G.; Wymbs, Fran A.; Pariseau, Meaghan E.; Belin, Peter J.; Waschbusch, Daniel A.; Babocsai, Lysett; Fabiano, Gregory A.; Akinnusi, Opeolowa O.; Haak, Jenifer L.; Pelham, William E.

    2013-01-01

    Objective: No psychosocial treatments have been developed for children with ADHD and severe mood dysregulation (SMD) despite the significant prevalence and morbidity of this combination. Therefore, the authors developed a novel treatment program for children with ADHD and SMD. Method: The novel therapy program integrates components of…

  7. Disruptive Mood Dysregulation Disorder Symptoms by Age in Autism, ADHD, and General Population Samples

    Science.gov (United States)

    Mayes, Susan Dickerson; Kokotovich, Cari; Mathiowetz, Christine; Baweja, Raman; Calhoun, Susan L.; Waxmonsky, James

    2017-01-01

    Disruptive mood dysregulation disorder (DMDD) is a controversial "DSM-5" diagnosis. It is not known how DMDD symptoms vary by age and if differences are similar for autism, ADHD, and general population samples. Our study analyzed the two DMDD symptoms (irritable-angry mood and temper outbursts) in 1,827 children with autism or ADHD (with…

  8. Genome-Wide Association Study of the Child Behavior Checklist Dysregulation Profile

    Science.gov (United States)

    Mick, Eric; McGough, James; Loo, Sandra; Doyle, Alysa E.; Wozniak, Janet; Wilens, Timothy E.; Smalley, Susan; McCracken, James; Biederman, Joseph; Faraone, Stephen V.

    2011-01-01

    Objective: A potentially useful tool for understanding the distribution and determinants of emotional dysregulation in children is a Child Behavior Checklist profile, comprising the Attention Problems, Anxious/Depressed, and Aggressive Behavior clinical subscales (CBCL-DP). The CBCL-DP indexes a heritable trait that increases susceptibility for…

  9. Metabolic dysregulation and interventions in type 2 diabetes mellitus and HIV-lipodystrophy

    NARCIS (Netherlands)

    Wijk, J.P.H. van

    2005-01-01

    The focus of this thesis is on two aspects of metabolic dysregulation, type 2 diabetes mellitus and HIV-lipodystrophy, and the effects of insulin-sensitizing agents. Thiazolidinediones (TZDs) have received increasing attenttion for the treatment of hyperglycemia in type 2 diabetes. Currently,

  10. Dysregulation of coronary microvascular reactivity in asymptomatic patients with type 2 diabetes mellitus

    Energy Technology Data Exchange (ETDEWEB)

    Momose, Mitsuru; Neverve, Jodi; Nekolla, Stephan G.; Schwaiger, Markus; Bengel, Frank M. [Nuklearmedizinische Klinik und Poliklinik der Technischen Universitaet Muenchen, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675 Munich (Germany); Abletshauser, Claudia [Department of Medicine, Novartis Pharma GmbH, Nuernberg (Germany); Schnell, Oliver; Standl, Eberhard [Institut fuer Diabetesforschung, Munich (Germany)

    2002-12-01

    In diabetic patients, a number of studies have suggested an impairment of vascular reactivity in response to vasodilatory stimuli. The pattern of dysregulation at the coronary microcirculatory level, however, has not been clearly defined. Thus, it was the aim of this study to characterise coronary microvascular function non-invasively in a homogeneous group of asymptomatic type 2 diabetic patients. In 46 patients with type 2 diabetes, myocardial blood flow (MBF) was quantified at baseline, in response to cold pressor test (CPT) and during adenosine-mediated vasodilation using positron emission tomography and nitrogen-13 ammonia. None of the patients had been treated with insulin, and none had symptoms of cardiac disease. Decreased MBF during CPT, indicating microvascular dysregulation, was observed in 16 patients (CPT-), while 30 patients demonstrated increased MBF during CPT (CPT+). Response to CPT was mildly, but significantly correlated with response to adenosine (r=0.44, P=0.0035). There was no difference in HbA1c, serum lipid levels or serum endothelial markers between the groups. Microvascular dysregulation in the CPT- group was associated with elevated baseline MBF (P<0.0001), reduced baseline vascular resistance (P=0.0026) and an abnormal increase in resistance during CPT (P=0.0002). In conclusion, coronary microvascular dysregulation is present in approximately one-third of asymptomatic, non-insulin-treated type 2 diabetic patients. Elevated baseline blood flow and reduced microvascular resistance at rest are characteristics of this dysregulation. These data suggest a state of activation of endothelial-dependent vasodilation at baseline which appears to limit the flow response to stress conditions. (orig.)

  11. Can Emotional and Behavioral Dysregulation in Youth Be Decoded from Functional Neuroimaging?

    Directory of Open Access Journals (Sweden)

    Liana C L Portugal

    Full Text Available High comorbidity among pediatric disorders characterized by behavioral and emotional dysregulation poses problems for diagnosis and treatment, and suggests that these disorders may be better conceptualized as dimensions of abnormal behaviors. Furthermore, identifying neuroimaging biomarkers related to dimensional measures of behavior may provide targets to guide individualized treatment. We aimed to use functional neuroimaging and pattern regression techniques to determine whether patterns of brain activity could accurately decode individual-level severity on a dimensional scale measuring behavioural and emotional dysregulation at two different time points.A sample of fifty-seven youth (mean age: 14.5 years; 32 males was selected from a multi-site study of youth with parent-reported behavioral and emotional dysregulation. Participants performed a block-design reward paradigm during functional Magnetic Resonance Imaging (fMRI. Pattern regression analyses consisted of Relevance Vector Regression (RVR and two cross-validation strategies implemented in the Pattern Recognition for Neuroimaging toolbox (PRoNTo. Medication was treated as a binary confounding variable. Decoded and actual clinical scores were compared using Pearson's correlation coefficient (r and mean squared error (MSE to evaluate the models. Permutation test was applied to estimate significance levels.Relevance Vector Regression identified patterns of neural activity associated with symptoms of behavioral and emotional dysregulation at the initial study screen and close to the fMRI scanning session. The correlation and the mean squared error between actual and decoded symptoms were significant at the initial study screen and close to the fMRI scanning session. However, after controlling for potential medication effects, results remained significant only for decoding symptoms at the initial study screen. Neural regions with the highest contribution to the pattern regression model

  12. Benchmarking pathway interaction network for colorectal cancer to identify dysregulated pathways

    Directory of Open Access Journals (Sweden)

    Q. Wang

    Full Text Available Different pathways act synergistically to participate in many biological processes. Thus, the purpose of our study was to extract dysregulated pathways to investigate the pathogenesis of colorectal cancer (CRC based on the functional dependency among pathways. Protein-protein interaction (PPI information and pathway data were retrieved from STRING and Reactome databases, respectively. After genes were aligned to the pathways, each pathway activity was calculated using the principal component analysis (PCA method, and the seed pathway was discovered. Subsequently, we constructed the pathway interaction network (PIN, where each node represented a biological pathway based on gene expression profile, PPI data, as well as pathways. Dysregulated pathways were then selected from the PIN according to classification performance and seed pathway. A PIN including 11,960 interactions was constructed to identify dysregulated pathways. Interestingly, the interaction of mRNA splicing and mRNA splicing-major pathway had the highest score of 719.8167. Maximum change of the activity score between CRC and normal samples appeared in the pathway of DNA replication, which was selected as the seed pathway. Starting with this seed pathway, a pathway set containing 30 dysregulated pathways was obtained with an area under the curve score of 0.8598. The pathway of mRNA splicing, mRNA splicing-major pathway, and RNA polymerase I had the maximum genes of 107. Moreover, we found that these 30 pathways had crosstalks with each other. The results suggest that these dysregulated pathways might be used as biomarkers to diagnose CRC.

  13. Maternal control and early child dysregulation: Moderating roles of ethnicity and child delay status.

    Science.gov (United States)

    Caplan, B; Baker, B L

    2017-02-01

    Maternal controlling behaviour has been found to influence child development, particularly in behavioural and emotional regulation. Given the higher rates of interfering parent control found in mothers of children with developmental delays (DD) and Latina mothers, their children could be at increased risk for behavioural and emotional dysregulation. While studies generally support this increased risk for children with DD, findings for Latino children are mixed and often attributed to cultural models of child rearing. The present study sought to determine the moderating roles of child DD and mother ethnicity in determining the relationships between two types of parent control (supportive directiveness and interference) and child dysregulation over time. The present study, involving 178 3-year old children with DD (n = 80) or typical development (n = 98), examined observed parent control (directive versus interfering) of Latina and Anglo mothers as it relates to change in preschool child dysregulation over 2 years. Interfering parent control was greater for children with DD and also for Latino mothers. Supportive directive parenting generally related to relatively greater decline in child behaviour and emotion dysregulation over time, while interfering parenting generally related to less decline in child behaviour dysregulation over time. In Anglo but not Latino families, these relationships tended to vary as a function of child disability. Parent directives that support, rather than deter, ongoing child activity may promote positive regulatory development. These results particularly hold for children with DD and Latino families, and have implications for parenting practices and intervention. © 2016 MENCAP and International Association of the Scientific Study of Intellectual and Developmental Disabilities and John Wiley & Sons Ltd.

  14. CLG for Automatic Image Segmentation

    OpenAIRE

    Christo Ananth; S.Santhana Priya; S.Manisha; T.Ezhil Jothi; M.S.Ramasubhaeswari

    2017-01-01

    This paper proposes an automatic segmentation method which effectively combines Active Contour Model, Live Wire method and Graph Cut approach (CLG). The aim of Live wire method is to provide control to the user on segmentation process during execution. Active Contour Model provides a statistical model of object shape and appearance to a new image which are built during a training phase. In the graph cut technique, each pixel is represented as a node and the distance between those nodes is rep...

  15. Market segmentation, targeting and positioning

    OpenAIRE

    Camilleri, Mark Anthony

    2017-01-01

    Businesses may not be in a position to satisfy all of their customers, every time. It may prove difficult to meet the exact requirements of each individual customer. People do not have identical preferences, so rarely does one product completely satisfy everyone. Many companies may usually adopt a strategy that is known as target marketing. This strategy involves dividing the market into segments and developing products or services to these segments. A target marketing strategy is focused on ...

  16. Automated bone segmentation from dental CBCT images using patch-based sparse representation and convex optimization

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Li; Gao, Yaozong; Shi, Feng; Liao, Shu; Li, Gang [Department of Radiology and BRIC, University of North Carolina at Chapel Hill, North Carolina 27599 (United States); Chen, Ken Chung [Department of Oral and Maxillofacial Surgery, Houston Methodist Hospital Research Institute, Houston, Texas 77030 and Department of Stomatology, National Cheng Kung University Medical College and Hospital, Tainan, Taiwan 70403 (China); Shen, Steve G. F.; Yan, Jin [Department of Oral and Craniomaxillofacial Surgery and Science, Shanghai Ninth People' s Hospital, Shanghai Jiao Tong University College of Medicine, Shanghai, China 200011 (China); Lee, Philip K. M.; Chow, Ben [Hong Kong Dental Implant and Maxillofacial Centre, Hong Kong, China 999077 (China); Liu, Nancy X. [Department of Oral and Maxillofacial Surgery, Houston Methodist Hospital Research Institute, Houston, Texas 77030 and Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology, Beijing, China 100050 (China); Xia, James J. [Department of Oral and Maxillofacial Surgery, Houston Methodist Hospital Research Institute, Houston, Texas 77030 (United States); Department of Surgery (Oral and Maxillofacial Surgery), Weill Medical College, Cornell University, New York, New York 10065 (United States); Department of Oral and Craniomaxillofacial Surgery and Science, Shanghai Ninth People' s Hospital, Shanghai Jiao Tong University College of Medicine, Shanghai, China 200011 (China); Shen, Dinggang, E-mail: dgshen@med.unc.edu [Department of Radiology and BRIC, University of North Carolina at Chapel Hill, North Carolina 27599 and Department of Brain and Cognitive Engineering, Korea University, Seoul, 136701 (Korea, Republic of)

    2014-04-15

    Purpose: Cone-beam computed tomography (CBCT) is an increasingly utilized imaging modality for the diagnosis and treatment planning of the patients with craniomaxillofacial (CMF) deformities. Accurate segmentation of CBCT image is an essential step to generate three-dimensional (3D) models for the diagnosis and treatment planning of the patients with CMF deformities. However, due to the poor image quality, including very low signal-to-noise ratio and the widespread image artifacts such as noise, beam hardening, and inhomogeneity, it is challenging to segment the CBCT images. In this paper, the authors present a new automatic segmentation method to address these problems. Methods: To segment CBCT images, the authors propose a new method for fully automated CBCT segmentation by using patch-based sparse representation to (1) segment bony structures from the soft tissues and (2) further separate the mandible from the maxilla. Specifically, a region-specific registration strategy is first proposed to warp all the atlases to the current testing subject and then a sparse-based label propagation strategy is employed to estimate a patient-specific atlas from all aligned atlases. Finally, the patient-specific atlas is integrated into amaximum a posteriori probability-based convex segmentation framework for accurate segmentation. Results: The proposed method has been evaluated on a dataset with 15 CBCT images. The effectiveness of the proposed region-specific registration strategy and patient-specific atlas has been validated by comparing with the traditional registration strategy and population-based atlas. The experimental results show that the proposed method achieves the best segmentation accuracy by comparison with other state-of-the-art segmentation methods. Conclusions: The authors have proposed a new CBCT segmentation method by using patch-based sparse representation and convex optimization, which can achieve considerably accurate segmentation results in CBCT

  17. Automated bone segmentation from dental CBCT images using patch-based sparse representation and convex optimization

    International Nuclear Information System (INIS)

    Wang, Li; Gao, Yaozong; Shi, Feng; Liao, Shu; Li, Gang; Chen, Ken Chung; Shen, Steve G. F.; Yan, Jin; Lee, Philip K. M.; Chow, Ben; Liu, Nancy X.; Xia, James J.; Shen, Dinggang

    2014-01-01

    Purpose: Cone-beam computed tomography (CBCT) is an increasingly utilized imaging modality for the diagnosis and treatment planning of the patients with craniomaxillofacial (CMF) deformities. Accurate segmentation of CBCT image is an essential step to generate three-dimensional (3D) models for the diagnosis and treatment planning of the patients with CMF deformities. However, due to the poor image quality, including very low signal-to-noise ratio and the widespread image artifacts such as noise, beam hardening, and inhomogeneity, it is challenging to segment the CBCT images. In this paper, the authors present a new automatic segmentation method to address these problems. Methods: To segment CBCT images, the authors propose a new method for fully automated CBCT segmentation by using patch-based sparse representation to (1) segment bony structures from the soft tissues and (2) further separate the mandible from the maxilla. Specifically, a region-specific registration strategy is first proposed to warp all the atlases to the current testing subject and then a sparse-based label propagation strategy is employed to estimate a patient-specific atlas from all aligned atlases. Finally, the patient-specific atlas is integrated into amaximum a posteriori probability-based convex segmentation framework for accurate segmentation. Results: The proposed method has been evaluated on a dataset with 15 CBCT images. The effectiveness of the proposed region-specific registration strategy and patient-specific atlas has been validated by comparing with the traditional registration strategy and population-based atlas. The experimental results show that the proposed method achieves the best segmentation accuracy by comparison with other state-of-the-art segmentation methods. Conclusions: The authors have proposed a new CBCT segmentation method by using patch-based sparse representation and convex optimization, which can achieve considerably accurate segmentation results in CBCT

  18. Recognition Using Classification and Segmentation Scoring

    National Research Council Canada - National Science Library

    Kimball, Owen; Ostendorf, Mari; Rohlicek, Robin

    1992-01-01

    .... We describe an approach to connected word recognition that allows the use of segmental information through an explicit decomposition of the recognition criterion into classification and segmentation scoring...

  19. Segmentation of British Sign Language (BSL): Mind the gap!

    NARCIS (Netherlands)

    Orfanidou, E.; McQueen, J.M.; Adam, R.; Morgan, G.

    2015-01-01

    This study asks how users of British Sign Language (BSL) recognize individual signs in connected sign sequences. We examined whether this is achieved through modality-specific or modality-general segmentation procedures. A modality-specific feature of signed languages is that, during continuous

  20. Segmenting memory colours

    OpenAIRE

    Fredembach, Clément; Estrada, Francisco; Süsstrunk, Sabine

    2008-01-01

    Memory colours refer to the colour of specific image classes that have the essential attribute of being perceived in a consistent manner by human observers. In colour correction or rendering tasks, this consistency implies that they have to be faithfully reproduced; their importance, in that respect, is greater than other regions in an image. Before these regions can be properly addressed, one must in general detect them. There are various schemes and attributes to do so, but the preferred me...

  1. PTBS segmentation scheme for synthetic aperture radar

    Science.gov (United States)

    Friedland, Noah S.; Rothwell, Brian J.

    1995-07-01

    The Image Understanding Group at Martin Marietta Technologies in Denver, Colorado has developed a model-based synthetic aperture radar (SAR) automatic target recognition (ATR) system using an integrated resource architecture (IRA). IRA, an adaptive Markov random field (MRF) environment, utilizes information from image, model, and neighborhood resources to create a discrete, 2D feature-based world description (FBWD). The IRA FBWD features are peak, target, background and shadow (PTBS). These features have been shown to be very useful for target discrimination. The FBWD is used to accrue evidence over a model hypothesis set. This paper presents the PTBS segmentation process utilizing two IRA resources. The image resource (IR) provides generic (the physics of image formation) and specific (the given image input) information. The neighborhood resource (NR) provides domain knowledge of localized FBWD site behaviors. A simulated annealing optimization algorithm is used to construct a `most likely' PTBS state. Results on simulated imagery illustrate the power of this technique to correctly segment PTBS features, even when vehicle signatures are immersed in heavy background clutter. These segmentations also suppress sidelobe effects and delineate shadows.

  2. OASIS is Automated Statistical Inference for Segmentation, with applications to multiple sclerosis lesion segmentation in MRI.

    Science.gov (United States)

    Sweeney, Elizabeth M; Shinohara, Russell T; Shiee, Navid; Mateen, Farrah J; Chudgar, Avni A; Cuzzocreo, Jennifer L; Calabresi, Peter A; Pham, Dzung L; Reich, Daniel S; Crainiceanu, Ciprian M

    2013-01-01

    Magnetic resonance imaging (MRI) can be used to detect lesions in the brains of multiple sclerosis (MS) patients and is essential for diagnosing the disease and monitoring its progression. In practice, lesion load is often quantified by either manual or semi-automated segmentation of MRI, which is time-consuming, costly, and associated with large inter- and intra-observer variability. We propose OASIS is Automated Statistical Inference for Segmentation (OASIS), an automated statistical method for segmenting MS lesions in MRI studies. We use logistic regression models incorporating multiple MRI modalities to estimate voxel-level probabilities of lesion presence. Intensity-normalized T1-weighted, T2-weighted, fluid-attenuated inversion recovery and proton density volumes from 131 MRI studies (98 MS subjects, 33 healthy subjects) with manual lesion segmentations were used to train and validate our model. Within this set, OASIS detected lesions with a partial area under the receiver operating characteristic curve for clinically relevant false positive rates of 1% and below of 0.59% (95% CI; [0.50%, 0.67%]) at the voxel level. An experienced MS neuroradiologist compared these segmentations to those produced by LesionTOADS, an image segmentation software that provides segmentation of both lesions and normal brain structures. For lesions, OASIS out-performed LesionTOADS in 74% (95% CI: [65%, 82%]) of cases for the 98 MS subjects. To further validate the method, we applied OASIS to 169 MRI studies acquired at a separate center. The neuroradiologist again compared the OASIS segmentations to those from LesionTOADS. For lesions, OASIS ranked higher than LesionTOADS in 77% (95% CI: [71%, 83%]) of cases. For a randomly selected subset of 50 of these studies, one additional radiologist and one neurologist also scored the images. Within this set, the neuroradiologist ranked OASIS higher than LesionTOADS in 76% (95% CI: [64%, 88%]) of cases, the neurologist 66% (95% CI: [52%, 78

  3. Automatic segmentation of the glenohumeral cartilages from magnetic resonance images

    International Nuclear Information System (INIS)

    Neubert, A.; Yang, Z.; Engstrom, C.; Xia, Y.; Strudwick, M. W.; Chandra, S. S.; Crozier, S.; Fripp, J.

    2016-01-01

    Purpose: Magnetic resonance (MR) imaging plays a key role in investigating early degenerative disorders and traumatic injuries of the glenohumeral cartilages. Subtle morphometric and biochemical changes of potential relevance to clinical diagnosis, treatment planning, and evaluation can be assessed from measurements derived from in vivo MR segmentation of the cartilages. However, segmentation of the glenohumeral cartilages, using approaches spanning manual to automated methods, is technically challenging, due to their thin, curved structure and overlapping intensities of surrounding tissues. Automatic segmentation of the glenohumeral cartilages from MR imaging is not at the same level compared to the weight-bearing knee and hip joint cartilages despite the potential applications with respect to clinical investigation of shoulder disorders. In this work, the authors present a fully automated segmentation method for the glenohumeral cartilages using MR images of healthy shoulders. Methods: The method involves automated segmentation of the humerus and scapula bones using 3D active shape models, the extraction of the expected bone–cartilage interface, and cartilage segmentation using a graph-based method. The cartilage segmentation uses localization, patient specific tissue estimation, and a model of the cartilage thickness variation. The accuracy of this method was experimentally validated using a leave-one-out scheme on a database of MR images acquired from 44 asymptomatic subjects with a true fast imaging with steady state precession sequence on a 3 T scanner (Siemens Trio) using a dedicated shoulder coil. The automated results were compared to manual segmentations from two experts (an experienced radiographer and an experienced musculoskeletal anatomist) using the Dice similarity coefficient (DSC) and mean absolute surface distance (MASD) metrics. Results: Accurate and precise bone segmentations were achieved with mean DSC of 0.98 and 0.93 for the humeral head

  4. Automatic segmentation of the glenohumeral cartilages from magnetic resonance images

    Energy Technology Data Exchange (ETDEWEB)

    Neubert, A., E-mail: ales.neubert@csiro.au [School of Information Technology and Electrical Engineering, University of Queensland, Brisbane 4072, Australia and The Australian E-Health Research Centre, CSIRO Health and Biosecurity, Brisbane 4029 (Australia); Yang, Z. [School of Information Technology and Electrical Engineering, University of Queensland, Brisbane 4072, Australia and Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190 (China); Engstrom, C. [School of Human Movement Studies, University of Queensland, Brisbane 4072 (Australia); Xia, Y.; Strudwick, M. W.; Chandra, S. S.; Crozier, S. [School of Information Technology and Electrical Engineering, University of Queensland, Brisbane 4072 (Australia); Fripp, J. [The Australian E-Health Research Centre, CSIRO Health and Biosecurity, Brisbane, 4029 (Australia)

    2016-10-15

    Purpose: Magnetic resonance (MR) imaging plays a key role in investigating early degenerative disorders and traumatic injuries of the glenohumeral cartilages. Subtle morphometric and biochemical changes of potential relevance to clinical diagnosis, treatment planning, and evaluation can be assessed from measurements derived from in vivo MR segmentation of the cartilages. However, segmentation of the glenohumeral cartilages, using approaches spanning manual to automated methods, is technically challenging, due to their thin, curved structure and overlapping intensities of surrounding tissues. Automatic segmentation of the glenohumeral cartilages from MR imaging is not at the same level compared to the weight-bearing knee and hip joint cartilages despite the potential applications with respect to clinical investigation of shoulder disorders. In this work, the authors present a fully automated segmentation method for the glenohumeral cartilages using MR images of healthy shoulders. Methods: The method involves automated segmentation of the humerus and scapula bones using 3D active shape models, the extraction of the expected bone–cartilage interface, and cartilage segmentation using a graph-based method. The cartilage segmentation uses localization, patient specific tissue estimation, and a model of the cartilage thickness variation. The accuracy of this method was experimentally validated using a leave-one-out scheme on a database of MR images acquired from 44 asymptomatic subjects with a true fast imaging with steady state precession sequence on a 3 T scanner (Siemens Trio) using a dedicated shoulder coil. The automated results were compared to manual segmentations from two experts (an experienced radiographer and an experienced musculoskeletal anatomist) using the Dice similarity coefficient (DSC) and mean absolute surface distance (MASD) metrics. Results: Accurate and precise bone segmentations were achieved with mean DSC of 0.98 and 0.93 for the humeral head

  5. Segmenting Chinese Tourists by the Expected Experience at Theme Parks

    Directory of Open Access Journals (Sweden)

    Shan Chen

    2013-08-01

    Full Text Available In this paper, we propose an experiential approach to tourist segmentation aimed at overcoming the limits of both socio-demographic and context-specific approaches widely adopted in the literature and in practice. In this study, segmentation is carried out based upon the expected experiences of Chinese tourists at the Shanghai World Exposition. The segmentation reveals four tourist clusters with different interests in relation to their experiences in visiting the World Exposition. The clusters showed insignificant differences in the demographics but proved to be powerfully discriminant in determining tourists’ satisfaction and loyalty, which affirms the potential of the tourist experience being a segmenting variable. Moreover, thanks to the analysis, an evaluation of the Shanghai World Exposition’s success in terms of visitors’ satisfaction is provided.

  6. Emotion dysregulation and dyadic conflict in depressed and typical adolescents: Evaluating concordance across psychophysiological and observational measures

    Science.gov (United States)

    Crowell, Sheila E.; Baucom, Brian R.; Yaptangco, Mona; Bride, Daniel; Hsiao, Ray; McCauley, Elizabeth; Beauchaine, Theodore P.

    2014-01-01

    Many depressed adolescents experience difficulty regulating their emotions. These emotion regulation difficulties appear to emerge in part from socialization processes within families and then generalize to other contexts. However, emotion dysregulation is typically assessed within the individual, rather than in the social relationships that shape and maintain dysregulation. In this study, we evaluated concordance of physiological and observational measures of emotion dysregulation during interpersonal conflict, using a multilevel actor-partner interdependence model (APIM). Participants were 75 mother-daughter dyads, including 50 depressed adolescents with or without a history of self-injury, and 25 typically developing controls. Behavior dysregulation was operationalized as observed aversiveness during a conflict discussion, and physiological dysregulation was indexed by respiratory sinus arrhythmia (RSA). Results revealed different patterns of concordance for control versus depressed participants. Controls evidenced a concordant partner (between-person) effect, and showed increased physiological regulation during minutes when their partner was more aversive. In contrast, clinical dyad members displayed a concordant actor (within-person) effect, becoming simultaneously physiologically and behaviorally dysregulated. Results inform current understanding of emotion dysregulation across multiple levels of analysis. PMID:24607894

  7. Emotion dysregulation and dyadic conflict in depressed and typical adolescents: evaluating concordance across psychophysiological and observational measures.

    Science.gov (United States)

    Crowell, Sheila E; Baucom, Brian R; Yaptangco, Mona; Bride, Daniel; Hsiao, Ray; McCauley, Elizabeth; Beauchaine, Theodore P

    2014-04-01

    Many depressed adolescents experience difficulty in regulating their emotions. These emotion regulation difficulties appear to emerge in part from socialization processes within families and then generalize to other contexts. However, emotion dysregulation is typically assessed within the individual, rather than in the social relationships that shape and maintain dysregulation. In this study, we evaluated concordance of physiological and observational measures of emotion dysregulation during interpersonal conflict, using a multilevel actor-partner interdependence model (APIM). Participants were 75 mother-daughter dyads, including 50 depressed adolescents with or without a history of self-injury, and 25 typically developing controls. Behavior dysregulation was operationalized as observed aversiveness during a conflict discussion, and physiological dysregulation was indexed by respiratory sinus arrhythmia (RSA). Results revealed different patterns of concordance for control versus depressed participants. Controls evidenced a concordant partner (between-person) effect, and showed increased physiological regulation during minutes when their partner was more aversive. In contrast, clinical dyad members displayed a concordant actor (within-person) effect, becoming simultaneously physiologically and behaviorally dysregulated. Results inform current understanding of emotion dysregulation across multiple levels of analysis. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Methods of evaluating segmentation characteristics and segmentation of major faults

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kie Hwa; Chang, Tae Woo; Kyung, Jai Bok [Seoul National Univ., Seoul (Korea, Republic of)] (and others)

    2000-03-15

    Seismological, geological, and geophysical studies were made for reasonable segmentation of the Ulsan fault and the results are as follows. One- and two- dimensional electrical surveys revealed clearly the fault fracture zone enlarges systematically northward and southward from the vicinity of Mohwa-ri, indicating Mohwa-ri is at the seismic segment boundary. Field Geological survey and microscope observation of fault gouge indicates that the Quaternary faults in the area are reactivated products of the preexisting faults. Trench survey of the Chonbuk fault Galgok-ri revealed thrust faults and cumulative vertical displacement due to faulting during the late Quaternary with about 1.1-1.9 m displacement per event; the latest event occurred from 14000 to 25000 yrs. BP. The seismic survey showed the basement surface os cut by numerous reverse faults and indicated the possibility that the boundary between Kyeongsangbukdo and Kyeongsannamdo may be segment boundary.

  9. Segmentation by Large Scale Hypothesis Testing - Segmentation as Outlier Detection

    DEFF Research Database (Denmark)

    Darkner, Sune; Dahl, Anders Lindbjerg; Larsen, Rasmus

    2010-01-01

    a microscope and we show how the method can handle transparent particles with significant glare point. The method generalizes to other problems. THis is illustrated by applying the method to camera calibration images and MRI of the midsagittal plane for gray and white matter separation and segmentation......We propose a novel and efficient way of performing local image segmentation. For many applications a threshold of pixel intensities is sufficient but determine the appropriate threshold value can be difficult. In cases with large global intensity variation the threshold value has to be adapted...... locally. We propose a method based on large scale hypothesis testing with a consistent method for selecting an appropriate threshold for the given data. By estimating the background distribution we characterize the segment of interest as a set of outliers with a certain probability based on the estimated...

  10. Methods of evaluating segmentation characteristics and segmentation of major faults

    International Nuclear Information System (INIS)

    Lee, Kie Hwa; Chang, Tae Woo; Kyung, Jai Bok

    2000-03-01

    Seismological, geological, and geophysical studies were made for reasonable segmentation of the Ulsan fault and the results are as follows. One- and two- dimensional electrical surveys revealed clearly the fault fracture zone enlarges systematically northward and southward from the vicinity of Mohwa-ri, indicating Mohwa-ri is at the seismic segment boundary. Field Geological survey and microscope observation of fault gouge indicates that the Quaternary faults in the area are reactivated products of the preexisting faults. Trench survey of the Chonbuk fault Galgok-ri revealed thrust faults and cumulative vertical displacement due to faulting during the late Quaternary with about 1.1-1.9 m displacement per event; the latest event occurred from 14000 to 25000 yrs. BP. The seismic survey showed the basement surface os cut by numerous reverse faults and indicated the possibility that the boundary between Kyeongsangbukdo and Kyeongsannamdo may be segment boundary

  11. Automatic segmentation of psoriasis lesions

    Science.gov (United States)

    Ning, Yang; Shi, Chenbo; Wang, Li; Shu, Chang

    2014-10-01

    The automatic segmentation of psoriatic lesions is widely researched these years. It is an important step in Computer-aid methods of calculating PASI for estimation of lesions. Currently those algorithms can only handle single erythema or only deal with scaling segmentation. In practice, scaling and erythema are often mixed together. In order to get the segmentation of lesions area - this paper proposes an algorithm based on Random forests with color and texture features. The algorithm has three steps. The first step, the polarized light is applied based on the skin's Tyndall-effect in the imaging to eliminate the reflection and Lab color space are used for fitting the human perception. The second step, sliding window and its sub windows are used to get textural feature and color feature. In this step, a feature of image roughness has been defined, so that scaling can be easily separated from normal skin. In the end, Random forests will be used to ensure the generalization ability of the algorithm. This algorithm can give reliable segmentation results even the image has different lighting conditions, skin types. In the data set offered by Union Hospital, more than 90% images can be segmented accurately.

  12. Transcriptome-wide mega-analyses reveal joint dysregulation of immunologic genes and transcription regulators in brain and blood in schizophrenia.

    Science.gov (United States)

    Hess, Jonathan L; Tylee, Daniel S; Barve, Rahul; de Jong, Simone; Ophoff, Roel A; Kumarasinghe, Nishantha; Tooney, Paul; Schall, Ulrich; Gardiner, Erin; Beveridge, Natalie Jane; Scott, Rodney J; Yasawardene, Surangi; Perera, Antionette; Mendis, Jayan; Carr, Vaughan; Kelly, Brian; Cairns, Murray; Tsuang, Ming T; Glatt, Stephen J

    2016-10-01

    The application of microarray technology in schizophrenia research was heralded as paradigm-shifting, as it allowed for high-throughput assessment of cell and tissue function. This technology was widely adopted, initially in studies of postmortem brain tissue, and later in studies of peripheral blood. The collective body of schizophrenia microarray literature contains apparent inconsistencies between studies, with failures to replicate top hits, in part due to small sample sizes, cohort-specific effects, differences in array types, and other confounders. In an attempt to summarize existing studies of schizophrenia cases and non-related comparison subjects, we performed two mega-analyses of a combined set of microarray data from postmortem prefrontal cortices (n=315) and from ex-vivo blood tissues (n=578). We adjusted regression models per gene to remove non-significant covariates, providing best-estimates of transcripts dysregulated in schizophrenia. We also examined dysregulation of functionally related gene sets and gene co-expression modules, and assessed enrichment of cell types and genetic risk factors. The identities of the most significantly dysregulated genes were largely distinct for each tissue, but the findings indicated common emergent biological functions (e.g. immunity) and regulatory factors (e.g., predicted targets of transcription factors and miRNA species across tissues). Our network-based analyses converged upon similar patterns of heightened innate immune gene expression in both brain and blood in schizophrenia. We also constructed generalizable machine-learning classifiers using the blood-based microarray data. Our study provides an informative atlas for future pathophysiologic and biomarker studies of schizophrenia. Published by Elsevier B.V.

  13. Skip segment Hirschsprung disease and Waardenburg syndrome

    Directory of Open Access Journals (Sweden)

    Erica R. Gross

    2015-04-01

    Full Text Available Skip segment Hirschsprung disease describes a segment of ganglionated bowel between two segments of aganglionated bowel. It is a rare phenomenon that is difficult to diagnose. We describe a recent case of skip segment Hirschsprung disease in a neonate with a family history of Waardenburg syndrome and the genetic profile that was identified.

  14. U.S. Army Custom Segmentation System

    Science.gov (United States)

    2007-06-01

    segmentation is individual or intergroup differences in response to marketing - mix variables. Presumptions about segments: •different demands in a...product or service category, •respond differently to changes in the marketing mix Criteria for segments: •The segments must exist in the environment

  15. Skip segment Hirschsprung disease and Waardenburg syndrome

    OpenAIRE

    Gross, Erica R.; Geddes, Gabrielle C.; McCarrier, Julie A.; Jarzembowski, Jason A.; Arca, Marjorie J.

    2015-01-01

    Skip segment Hirschsprung disease describes a segment of ganglionated bowel between two segments of aganglionated bowel. It is a rare phenomenon that is difficult to diagnose. We describe a recent case of skip segment Hirschsprung disease in a neonate with a family history of Waardenburg syndrome and the genetic profile that was identified.

  16. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

    Directory of Open Access Journals (Sweden)

    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II

  17. A Novel Iris Segmentation Scheme

    Directory of Open Access Journals (Sweden)

    Chen-Chung Liu

    2014-01-01

    Full Text Available One of the key steps in the iris recognition system is the accurate iris segmentation from its surrounding noises including pupil, sclera, eyelashes, and eyebrows of a captured eye-image. This paper presents a novel iris segmentation scheme which utilizes the orientation matching transform to outline the outer and inner iris boundaries initially. It then employs Delogne-Kåsa circle fitting (instead of the traditional Hough transform to further eliminate the outlier points to extract a more precise iris area from an eye-image. In the extracted iris region, the proposed scheme further utilizes the differences in the intensity and positional characteristics of the iris, eyelid, and eyelashes to detect and delete these noises. The scheme is then applied on iris image database, UBIRIS.v1. The experimental results show that the presented scheme provides a more effective and efficient iris segmentation than other conventional methods.

  18. Chronic complex dissociative disorders and borderline personality disorder: disorders of emotion dysregulation?

    Science.gov (United States)

    Brand, Bethany L; Lanius, Ruth A

    2014-01-01

    Emotion dysregulation is a core feature of chronic complex dissociative disorders (DD), as it is for borderline personality disorder (BPD). Chronic complex DD include dissociative identity disorder (DID) and the most common form of dissociative disorder not otherwise specified (DDNOS, type 1), now known as Other Specified Dissociative Disorders (OSDD, type 1). BPD is a common comorbid disorder with DD, although preliminary research indicates the disorders have some distinguishing features as well as considerable overlap. This article focuses on the epidemiology, clinical presentation, psychological profile, treatment, and neurobiology of chronic complex DD with emphasis placed on the role of emotion dysregulation in each of these areas. Trauma experts conceptualize borderline symptoms as often being trauma based, as are chronic complex DD. We review the preliminary research that compares DD to BPD in the hopes that this will stimulate additional comparative research.

  19. Dysregulated miR-183 inhibits migration in breast cancer cells.

    LENUS (Irish Health Repository)

    Lowery, Aoife J

    2010-01-01

    The involvement of miRNAs in the regulation of fundamental cellular functions has placed them at the fore of ongoing investigations into the processes underlying carcinogenesis. MiRNA expression patterns have been shown to be dysregulated in numerous human malignancies, including breast cancer, suggesting their probable involvement as novel classes of oncogenes or tumour suppressor genes. The identification of differentially expressed miRNAs and elucidation of their functional roles may provide insight into the complex and diverse molecular mechanisms of tumorigenesis. MiR-183 is located on chromosome 7q32 and is part of a miRNA family which are dysregulated in numerous cancers. The aims of this study were to further examine the expression and functional role of miR-183 in breast cancer.

  20. Immune System Dysregulation, Viral Reactivation and Stress During Short-Duration Space Flight

    Science.gov (United States)

    Crucian, Brian; Mehta, Satish; Stowe, Raymond; Uchakin, Peter; Quiriarte, Heather; Pierson, Duane; Sams, Clarence

    2010-01-01

    This slide presentation reviews a study that was conducted to ascertain if the immune system dysregulation, viral reactivation and stress from short duration space flight were a result of the stress of landing and readjustment to gravity. The objectives of the study were to replace several recent immune studies with one comprehensive study that will include in-flight sampling; address lack of in-flight data: (i.e., determine the in-flight status of immunity, physiological stress, viral immunity/reactivation); determine the clinical risk related to immune dysregulation for exploration class spaceflight; and determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

  1. Mild KCC2 hypofunction causes inconspicuous chloride dysregulation that degrades neural coding

    Directory of Open Access Journals (Sweden)

    Nicolas eDoyon

    2016-01-01

    Full Text Available Disinhibition caused by Cl- dysregulation is implicated in several neurological disorders. This form of disinhibition, which stems primarily from impaired Cl- extrusion through the co-transporter KCC2, is typically identified by a depolarizing shift in GABA reversal potential (EGABA. Here we show, using computer simulations, that intracellular [Cl-] exhibits exaggerated fluctuations during transient Cl- loads and recovers more slowly to baseline when KCC2 level is even modestly reduced. Using information theory and signal detection theory, we show that increased Cl- lability and settling time degrade neural coding. Importantly, these deleterious effects manifest after less KCC2 reduction than needed to produce the gross changes in EGABA required for detection by most experiments, which assess KCC2 function under weak Cl- load conditions. By demonstrating the existence and functional consequences of occult Cl- dysregulation, these results suggest that modest KCC2 hypofunction plays a greater role in neurological disorders than previously believed.

  2. The Pathogenesis and Treatment of Emotion Dysregulation in Borderline Personality Disorder

    Directory of Open Access Journals (Sweden)

    Andreas Laddis

    2015-01-01

    Full Text Available Uncontrollable emotional lability and impulsivity are a paramount phenomenon of Borderline Personality Disorder (BPD. This paper aims to review theories that entertain emotion dysregulation as the core deficit of BPD and a key factor in the etiology of BPD, in order, then, to propose the author’s own theory, which arguably transcends certain limitations of the earlier ones. The author asserts that his psychodynamic theory explains the symptoms of BPD more thoroughly and it inspires a more parsimonious interpretation of brain imaging findings. In closing, the author draws implications of the proposed theory for clinical practice. He reports an efficacy study for treatment of emotion dysregulation based on that theory.

  3. Dysregulated proinflammatory and fibrogenic phenotype of fibroblasts in cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    François Huaux

    Full Text Available Morbi-mortality in cystic fibrosis (CF is mainly related to chronic lung infection and inflammation, uncontrolled tissue rearrangements and fibrosis, and yet the underlying mechanisms remain largely unknown. We evaluated inflammatory and fibrosis responses to bleomycin in F508del homozygous and wild-type mice, and phenotype of fibroblasts explanted from mouse lungs and skin. The effect of vardenafil, a cGMP-specific phosphodiesterase type 5 inhibitor, was tested in vivo and in culture. Responses of proinflammatory and fibrotic markers to bleomycin were enhanced in lungs and skin of CF mice and were prevented by treatment with vardenafil. Purified lung and skin fibroblasts from CF mice proliferated and differentiated into myofibroblasts more prominently and displayed higher sensitivity to growth factors than those recovered from wild-type littermates. Under inflammatory stimulation, mRNA and protein expression of proinflammatory mediators were higher in CF than in wild-type fibroblasts, in which CFTR expression reached similar levels to those observed in other non-epithelial cells, such as macrophages. Increased proinflammatory responses in CF fibroblasts were reduced by half with submicromolar concentrations of vardenafil. Proinflammatory and fibrogenic functions of fibroblasts are upregulated in CF and are reduced by vardenafil. This study provides compelling new support for targeting cGMP signaling pathway in CF pharmacotherapy.

  4. Evaluation of segmental left ventricular wall motion by equilibrium gated radionuclide ventriculography.

    Science.gov (United States)

    Van Nostrand, D; Janowitz, W R; Holmes, D R; Cohen, H A

    1979-01-01

    The ability of equilibrium gated radionuclide ventriculography to detect segmental left ventricular (LV) wall motion abnormalities was determined in 26 patients undergoing cardiac catheterization. Multiple gated studies obtained in 30 degrees right anterior oblique and 45 degrees left anterior oblique projections, played back in a movie format, were compared to the corresponding LV ventriculograms. The LV wall in the two projections was divided into eight segments. Each segment was graded as normal, hypokinetic, akinetic, dyskinetic, or indeterminate. Thirteen percent of the segments in the gated images were indeterminate; 24 out of 27 of these were proximal or distal inferior wall segments. There was exact agreement in 86% of the remaining segments. The sensitivity of the radionuclide technique for detecting normal versus any abnormal wall motion was 71%, with a specificity of 99%. Equilibrium gated ventriculography is an excellent noninvasive technique for evaluating segmental LV wall motion. It is least reliable in assessing the proximal inferior wall and interventricular septum.

  5. Document segmentation via oblique cuts

    Science.gov (United States)

    Svendsen, Jeremy; Branzan-Albu, Alexandra

    2013-01-01

    This paper presents a novel solution for the layout segmentation of graphical elements in Business Intelligence documents. We propose a generalization of the recursive X-Y cut algorithm, which allows for cutting along arbitrary oblique directions. An intermediate processing step consisting of line and solid region removal is also necessary due to presence of decorative elements. The output of the proposed segmentation is a hierarchical structure which allows for the identification of primitives in pie and bar charts. The algorithm was tested on a database composed of charts from business documents. Results are very promising.

  6. Optimally segmented permanent magnet structures

    DEFF Research Database (Denmark)

    Insinga, Andrea Roberto; Bjørk, Rasmus; Smith, Anders

    2016-01-01

    We present an optimization approach which can be employed to calculate the globally optimal segmentation of a two-dimensional magnetic system into uniformly magnetized pieces. For each segment the algorithm calculates the optimal shape and the optimal direction of the remanent flux density vector......, with respect to a linear objective functional. We illustrate the approach with results for magnet design problems from different areas, such as a permanent magnet electric motor, a beam focusing quadrupole magnet for particle accelerators and a rotary device for magnetic refrigeration....

  7. Rapid-Onset Obesity with Hypothalamic Dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD) Syndrome: A Case Report

    OpenAIRE

    Bagheri; Pourbakhtyaran; Talebi Kiasari; Taherkhanchi; Salarian; Sadeghi

    2016-01-01

    Introduction Rapid-onset obesity with hypoventilation, hypothalamic dysfunction, and autonomic dysregulation (ROHHAD) is a rare disease. To date, there have been only few reported cases of ROHHAD syndrome. Case Presentation We report a 5-year-old- Iranian girl who had normal growth and development until her 4th year of life. At that time, the patient developed weight gain, constipation, coldness in the extremities, and hyperhidros...

  8. Dysregulation of angiopoietins is associated with placental malaria and low birth weight.

    Directory of Open Access Journals (Sweden)

    Karlee L Silver

    Full Text Available BACKGROUND: Placental malaria (PM is associated with adverse pregnancy outcomes including low birth weight (LBW. However, the precise mechanisms by which PM induces LBW are poorly defined. Based on the essential role of angiopoietin (ANG-1 and -2 in normal placental vascular development, we hypothesized that PM may result in the dysregulation of angiopoietins and thereby contribute to LBW outcomes. METHODS AND FINDINGS: In a mouse model of PM, we show that Plasmodium berghei ANKA infection of pregnant mice resulted in dysregulated angiopoietin levels and fetal growth restriction. PM lead to decreased ANG-1, increased ANG-2, and an elevated ratio of ANG-2/ANG-1 in the placenta and the serum. These observations were extended to malaria-exposed pregnant women: In a study of primigravid women prospectively followed over the course of pregnancy, Plasmodium falciparum infection was associated with a decrease in maternal plasma ANG-1 levels (P = 0.031 and an increase in the ANG-2:ANG-1 ratio (P = 0.048. ANG-1 levels recovered with successful treatment of peripheral parasitemia (P = 0.010. In a cross-sectional study of primigravidae at delivery, angiopoietin dysregulation was associated with PM (P = 0.002 and LBW (P = 0.041. Women with PM who delivered LBW infants had increased ANG-2:ANG-1 ratios (P = 0.002 compared to uninfected women delivering normal birth weight infants. CONCLUSIONS: These data support the hypothesis that dysregulation of angiopoietins is associated with PM and LBW outcomes, and suggest that ANG-1 and ANG-2 levels may be clinically informative biomarkers to identify P. falciparum-infected mothers at risk of LBW deliveries.

  9. Emotion Dysregulation and Anxiety in Adults with ASD: Does Social Motivation Play a Role?

    OpenAIRE

    Swain, Deanna; Scarpa-Friedman, Angela; White, Susan; Laugeson, Elizabeth

    2015-01-01

    Young adults with ASD and no intellectual impairment are more likely to exhibit clinical levels of anxiety than typically developing peers (DSM-5, American Psychiatric Association, 2013). This study tests a mechanistic model in which anxiety culminates via emotion dysregulation and social motivation. Adults with ASD (49 males, 20 females) completed self-report measures on emotion regulation, caregivers completed measures on ASD severity and both on social anxiety. Results indicated that emoti...

  10. Cell cycle pathway dysregulation in human keratinocytes during chronic exposure to low arsenite.

    Science.gov (United States)

    Al-Eryani, Laila; Waigel, Sabine; Jala, Venkatakrishna; Jenkins, Samantha F; States, J Christopher

    2017-09-15

    Arsenic is naturally prevalent in the earth's crust and widely distributed in air and water. Chronic low arsenic exposure is associated with several cancers in vivo, including skin cancer, and with transformation in vitro of cell lines including immortalized human keratinocytes (HaCaT). Arsenic also is associated with cell cycle dysregulation at different exposure levels in multiple cell lines. In this work, we analyzed gene expression in HaCaT cells to gain an understanding of gene expression changes contributing to transformation at an early time point. HaCaT cells were exposed to 0 or 100nM NaAsO 2 for 7weeks. Total RNA was purified and analyzed by microarray hybridization. Differential expression with fold change≥|1.5| and p-value≤0.05 was determined using Partek Genomic Suite™ and pathway and network analyses using MetaCore™ software (FDR≤0.05). Cell cycle analysis was performed using flow cytometry. 644 mRNAs were differentially expressed. Cell cycle/cell cycle regulation pathways predominated in the list of dysregulated pathways. Genes involved in replication origin licensing were enriched in the network. Cell cycle assay analysis showed an increase in G2/M compartment in arsenite-exposed cells. Arsenite exposure induced differential gene expression indicating dysregulation of cell cycle control, which was confirmed by cell cycle analysis. The results suggest that cell cycle dysregulation is an early event in transformation manifested in cells unable to transit G2/M efficiently. Further study at later time points will reveal additional changes in gene expression related to transformation processes. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Dysregulation of the unfolded protein response in db/db mice with diet induced steatohepatitis

    OpenAIRE

    Rinella, Mary E.; Siddiqui, M. Shaddab; Gardikiotes, Konstantina; Gottstein, Jeanne; Elias, Marc; Green, Richard M.

    2011-01-01

    In humans with non-alcoholic fatty liver, diabetes is associated with more advanced disease. We have previously shown that diabetic db/db mice are highly susceptible to methionine choline deficient diet (MCD) induced hepatic injury. Since activation of the unfolded protein response (UPR) is an important adaptive cellular mechanism in diabetes, obesity and fatty liver, we hypothesized that dysregulation of the UPR may partially explain how diabetes could promote liver injury.

  12. Blood Glucose and Insulin Concentrations after Octreotide Administration in Horses With Insulin Dysregulation

    OpenAIRE

    Frank, N.; Hermida, P.; Sanchez?Londo?o, A.; Singh, R.; Gradil, C.M.; Uricchio, C.K.

    2017-01-01

    Background Octreotide is a somatostatin analog that suppresses insulin secretion. Hypothesis We hypothesized that octreotide would suppress insulin concentrations in horses and that normal (N) horses and those with insulin dysregulation (ID) would differ significantly in their plasma glucose and insulin responses to administration of octreotide. Animals Twelve horses, N = 5, ID = 7. Methods Prospective study. An oral sugar test was performed to assign horses to N and ID groups. Octreotide (1....

  13. Intercalary bone segment transport in treatment of segmental tibial defects

    International Nuclear Information System (INIS)

    Iqbal, A.; Amin, M.S.

    2002-01-01

    Objective: To evaluate the results and complications of intercalary bone segment transport in the treatment of segmental tibial defects. Design: This is a retrospective analysis of patients with segmental tibial defects who were treated with intercalary bone segment transport method. Place and Duration of Study: The study was carried out at Combined Military Hospital, Rawalpindi from September 1997 to April 2001. Subjects and methods: Thirteen patients were included in the study who had developed tibial defects either due to open fractures with bone loss or subsequent to bone debridement of infected non unions. The mean bone defect was 6.4 cms and there were eight associated soft tissue defects. Locally made unilateral 'Naseer-Awais' (NA) fixator was used for bone segment transport. The distraction was done at the rate of 1mm/day after 7-10 days of osteotomy. The patients were followed-up fortnightly during distraction and monthly thereafter. The mean follow-up duration was 18 months. Results: The mean time in external fixation was 9.4 months. The m ean healing index' was 1.47 months/cm. Satisfactory union was achieved in all cases. Six cases (46.2%) required bone grafting at target site and in one of them grafting was required at the level of regeneration as well. All the wounds healed well with no residual infection. There was no residual leg length discrepancy of more than 20 mm nd one angular deformity of more than 5 degrees. The commonest complication encountered was pin track infection seen in 38% of Shanz Screws applied. Loosening occurred in 6.8% of Shanz screws, requiring re-adjustment. Ankle joint contracture with equinus deformity and peroneal nerve paresis occurred in one case each. The functional results were graded as 'good' in seven, 'fair' in four, and 'poor' in two patients. Overall, thirteen patients had 31 (minor/major) complications with a ratio of 2.38 complications per patient. To treat the bone defects and associated complications, a mean of

  14. Emotion Dysregulation Mediates Between Childhood Emotional Abuse and Motives for Substance Use.

    Science.gov (United States)

    Barahmand, Usha; Khazaee, Ali; Hashjin, Goudarz Sadeghi

    2016-12-01

    The purpose of this study is to assess the relative mediating effects of impulsivity and emotion dysregulation in the relationship between childhood maltreatment and motives for opiate use. Seventy four adolescent users of Tramadol, a synthetic opiate, were recruited from a boot camp for de-addiction and rehabilitation services for the study. Data were collected between May, 2014 and November, 2014. Participants completed assessments of childhood abuse history, difficulties regulating emotions, impulsiveness and motives for substance use as well as a socio-demographic information sheet. The results of the current study indicate that types of abuse may be associated with particular outcomes and can inform treatment planning for substance users. Findings from bootstrap mediator analyses indicated that emotion dysregulation, but not impulsiveness, mediated the relationship between childhood emotional abuse and expansion and enhancement motives for substance use. The current study provides preliminary evidence that difficulties regulating emotions may function as a mechanism linking prior childhood experiences of emotional abuse to subsequent motives for substance use. Clinical implications of these findings suggest that targeting emotion dysregulation problems may be an effective adjunct in the treatment of childhood emotional abuse adolescent victims at risk for substance use. Published by Elsevier Inc.

  15. Cross-population validation of statistical distance as a measure of physiological dysregulation during aging.

    Science.gov (United States)

    Cohen, Alan A; Milot, Emmanuel; Li, Qing; Legault, Véronique; Fried, Linda P; Ferrucci, Luigi

    2014-09-01

    Measuring physiological dysregulation during aging could be a key tool both to understand underlying aging mechanisms and to predict clinical outcomes in patients. However, most existing indices are either circular or hard to interpret biologically. Recently, we showed that statistical distance of 14 common blood biomarkers (a measure of how strange an individual's biomarker profile is) was associated with age and mortality in the WHAS II data set, validating its use as a measure of physiological dysregulation. Here, we extend the analyses to other data sets (WHAS I and InCHIANTI) to assess the stability of the measure across populations. We found that the statistical criteria used to determine the original 14 biomarkers produced diverging results across populations; in other words, had we started with a different data set, we would have chosen a different set of markers. Nonetheless, the same 14 markers (or the subset of 12 available for InCHIANTI) produced highly similar predictions of age and mortality. We include analyses of all combinatorial subsets of the markers and show that results do not depend much on biomarker choice or data set, but that more markers produce a stronger signal. We conclude that statistical distance as a measure of physiological dysregulation is stable across populations in Europe and North America. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Adult attachment, emotion dysregulation, and symptoms of depression and generalized anxiety disorder.

    Science.gov (United States)

    Marganska, Anna; Gallagher, Michelle; Miranda, Regina

    2013-01-01

    Differences in attachment style have been linked to both emotion regulation and psychological functioning, but the emotion regulatory mechanism through which attachment style might impact symptoms of depression and anxiety is unclear. The present study examined the explanatory role of emotion dysregulation in the relation between adult attachment style and symptoms of depression and generalized anxiety disorder (GAD) in a sample of 284 adults. Secure attachment was associated with lower depression and GAD symptoms and lower emotion dysregulation, whereas insecure attachment styles were generally associated with higher depression and GAD scores and higher emotion dysregulation. Perceived inability to generate effective emotion regulation strategies mediated the relation between insecure attachment and both depression and GAD symptoms. Nonacceptance of negative emotions and inability to control impulsive behaviors emerged as additional mediators of the relation between insecure attachment styles and GAD symptoms. The differential contribution of attachment style and emotion regulation to the prediction of depression and GAD symptoms may reflect differences in vulnerability to depression and GAD. © 2013 American Orthopsychiatric Association.

  17. Social exposure and emotion dysregulation: Main effects in relation to nonsuicidal self-injury.

    Science.gov (United States)

    Zelkowitz, Rachel L; Porter, Andrew C; Heiman, Ellen R; Cole, David A

    2017-10-01

    We examined the relation of interpersonal and media exposure to nonsuicidal self-injury (NSSI) among 340 university students in the southeastern United States (73.5% female, M age = 19.38 years, SD = 1.15). We also assessed interactions and main effects of each exposure and emotion dysregulation in relation to NSSI, testing the social learning hypothesis of NSSI. Most participants endorsed medium to high levels of exposure to NSSI via media sources. More than one-third of participants were somewhat or very familiar with someone who engaged in NSSI. Almost half reported occasional or frequent conversations about NSSI. Both exposure forms were significantly related to NSSI history. However, hurdle regression analyses revealed that interpersonal exposure and emotion dysregulation, but not media exposure, were significantly associated with NSSI history and frequency. We did not find evidence for an emotion dysregulation-by-interpersonal-exposure interaction. We discuss implications for theoretical models of NSSI, limitations, and future directions. Copyright © 2017. Published by Elsevier Ltd.

  18. Immune System Dysregulation and Latent Herpesvirus Reactivation During Winterover at Concordia Station, Dome C, Antarctica

    Science.gov (United States)

    Crucian, B. E.; Feuerecker, M.; Salam, A. P.; Rybka, A.; Stowe, R. P.; Morrels, M.; Meta, S. K.; Quiriarte, H.; Quintens, Roel; Thieme, U.; hide

    2011-01-01

    Immune system dysregulation occurs during spaceflight and consists of altered peripheral leukocyte distribution, reductions in immunocyte function and altered cytokine production profiles. Causes may include stress, confinement, isolation, and disrupted circadian rhythms. All of these factors may be replicated to some degree in terrestrial environments. NASA is currently evaluating the potential for a ground-based analog for immune dysregulation, which would have utility for mechanistic investigations and countermeasures evaluation. For ground-based space physiology research, the choice of terrestrial analog must carefully match the system of interest. Antarctica winter-over, consisting of prolonged durations in an extreme/dangerous environment, station-based habitation, isolation and disrupted circadian rhythms, is potentially a good ground-analog for spaceflight-associated immune dysregulation. Of all Antarctica bases, the French-Italian Concordia Station, may be the most appropriate to replicate spaceflight/exploration conditions. Concordia is an interior base located in harsh environmental conditions, and has been constructed to house small, international crews in a station-environment similar to what should be experienced by deep space astronauts. The ESA-NASA CHOICE study assessed innate and adaptive immunity, viral reactivation and stress factors during Concordia winterover deployment. The study was conducted over two winterover missions in 2009 and 2010. Final study data from NASA participation in these missions will be presented.

  19. Antireward, compulsivity, and addiction: seminal contributions of Dr. Athina Markou to motivational dysregulation in addiction.

    Science.gov (United States)

    Koob, George F

    2017-05-01

    Addiction is defined as a chronically relapsing disorder characterized by compulsive drug seeking that is hypothesized to derive from multiple sources of motivational dysregulation. Dr. Athina Markou made seminal contributions to our understanding of the neurobiology of addiction with her studies on the dysregulation of reward function using animal models with construct validity. Repeated overstimulation of the reward systems with drugs of abuse decreases reward function, characterized by brain stimulation reward and presumbably reflecting dysphoria-like states. The construct of negative reinforcement, defined as drug taking that alleviates a negative emotional state that is created by drug abstinence, is particularly relevant as a driving force in both the withdrawal/negative affect and preoccupation/anticipation stages of the addiction cycle. The negative emotional state that drives such negative reinforcement is hypothesized to derive from the dysregulation of key neurochemical circuits that drive incentive-salience/reward systems (dopamine, opioid peptides) in the ventral striatum and from the recruitment of brain stress systems (corticotropin-releasing factor, dynorphin) within the extended amygdala. As drug taking becomes compulsive-like, the factors that motivate behavior are hypothesized to shift to drug-seeking behavior that is driven not only by positive reinforcement but also by negative reinforcement. This shift in motivation is hypothesized to reflect the allostatic misregulation of hedonic tone such that drug taking makes the hedonic negative emotional state worse during the process of seeking temporary relief with compulsive drug taking.

  20. The child behavior checklist dysregulation profile predicts adolescent DSM-5 pathological personality traits 4 years later.

    Science.gov (United States)

    De Caluwé, Elien; Decuyper, Mieke; De Clercq, Barbara

    2013-07-01

    Emotional dysregulation in childhood has been associated with various forms of later psychopathology, although no studies have investigated the personality related adolescent outcomes associated with early emotional dysregulation. The present study uses a typological approach to examine how the child behavior checklist-dysregulation profile (CBCL-DP) predicts DSM-5 pathological personality traits (as measured with the personality inventory for the diagnostic and statistical manual of mental disorders 5 or PID-5 by Krueger et al. (Psychol Med 2012)) across a time span of 4 years in a sample of 243 children aged 8-14 years (57.2 % girls). The results showed that children assigned to the CBCL-DP class are at risk for elevated scores on a wide range of DSM-5 personality pathology features, including higher scores on hostility, risk taking, deceitfulness, callousness, grandiosity, irresponsibility, impulsivity and manipulativeness. These results are discussed in the context of identifying early manifestations of persistent regulation problems, because of their enduring impact on a child's personality development.

  1. Cardiac mTORC1 Dysregulation Impacts Stress Adaptation and Survival in Huntington’s Disease

    Directory of Open Access Journals (Sweden)

    Daniel D. Child

    2018-04-01

    Full Text Available Summary: Huntington’s disease (HD is a dominantly inherited neurological disorder caused by CAG-repeat expansion in exon 1 of Huntingtin (HTT. But in addition to the neurological disease, mutant HTT (mHTT, which is ubiquitously expressed, impairs other organ systems. Indeed, epidemiological and animal model studies suggest higher incidence of and mortality from heart disease in HD. Here, we show that the protein complex mTORC1 is dysregulated in two HD mouse models through a mechanism that requires intrinsic mHTT expression. Moreover, restoring cardiac mTORC1 activity with constitutively active Rheb prevents mortality and relieves the mHTT-induced block to hypertrophic adaptation to cardiac stress. Finally, we show that chronic mTORC1 dysregulation is due in part to mislocalization of endogenous Rheb. These data provide insight into the increased cardiac-related mortality of HD patients, with cardiac mHTT expression inhibiting mTORC1 activity, limiting heart growth, and decreasing the heart’s ability to compensate to chronic stress. : Child et al. demonstrate that mTORC1 dysregulation is a key molecular mechanism in the Huntington’s disease (HD heart phenotype. Impaired cardiac mTORC1 activity in HD mouse models requires intrinsic mHTT expression and explains the limited adaptation to cardiac stress. Keywords: Huntington’s disease, heart, mTOR, Rheb

  2. Hydrophilic segmented block copolymers based on poly(ethylene oxide) and monodisperse amide segments

    NARCIS (Netherlands)

    Husken, D.; Feijen, Jan; Gaymans, R.J.

    2007-01-01

    Segmented block copolymers based on poly(ethylene oxide) (PEO) flexible segments and monodisperse crystallizable bisester tetra-amide segments were made via a polycondensation reaction. The molecular weight of the PEO segments varied from 600 to 4600 g/mol and a bisester tetra-amide segment (T6T6T)

  3. Specificity of Facial Expression Labeling Deficits in Childhood Psychopathology

    Science.gov (United States)

    Guyer, Amanda E.; McClure, Erin B.; Adler, Abby D.; Brotman, Melissa A.; Rich, Brendan A.; Kimes, Alane S.; Pine, Daniel S.; Ernst, Monique; Leibenluft, Ellen

    2007-01-01

    Background: We examined whether face-emotion labeling deficits are illness-specific or an epiphenomenon of generalized impairment in pediatric psychiatric disorders involving mood and behavioral dysregulation. Method: Two hundred fifty-two youths (7-18 years old) completed child and adult facial expression recognition subtests from the Diagnostic…

  4. Metacognitions or distress intolerance: The mediating role in the relationship between emotional dysregulation and problematic internet use.

    Science.gov (United States)

    Akbari, Mehdi

    2017-12-01

    Given the relevance of problematic Internet use (PIU) to everyday life, its relationship to emotional dysregulation and the importance of metacognitions and distress intolerance in process and intermediaries research, this study examined which of metacognitions and distress intolerance acts as an intermediary between emotional dysregulation and PIU. In the current study, 413 undergraduate students from the University of Tehran, Iran (202 females; mean age = 20.13) voluntarily completed a questionnaire package which included the Internet Addiction Test (IAT), Difficulties in Emotion Regulation Scale (DERS), Metacognitions Questionnaire 30 (MCQ-30(, and Distress Tolerance Scale (DTS). The data were then analyzed using structural equation modeling by LISREL software. Significant correlations were found between PIU and emotional dysregulation and both distress intolerance and metacognitions ( P  intolerance. Also, these findings emphasize that distress intolerance has a more significant mediating role than metacognition in the relationship between emotional dysregulation and PIU.

  5. Longitudinal pathways from early maternal depression to children's dysregulated representations: a moderated mediation analysis of harsh parenting and gender.

    Science.gov (United States)

    Martoccio, Tiffany L; Brophy-Herb, Holly E; Maupin, Angela N; Robinson, Joann L

    2016-01-01

    There is some evidence linking maternal depression, harsh parenting, and children's internal representations of attachment, yet, longitudinal examinations of these relationships and differences in the developmental pathways between boys and girls are lacking. Moderated mediation growth curves were employed to examine harsh parenting as a mechanism underlying the link between maternal depression and children's dysregulated representations using a nationally-representative, economically-vulnerable sample of mothers and their children (n = 575; 49% boys, 51% girls). Dysregulation representations were measured using the MacArthur Story Stem Battery at five years of age (M = 5.14, SD = 0.29). Harsh parenting mediated the association between early maternal depression and dysregulated representations for girls. Though initial harsh parenting was a significant mediator for boys, a stronger direct effect of maternal depression to dysregulated representations emerged over time. Results are discussed in terms of their implications for intervention efforts aimed at promoting early supportive parenting.

  6. Segmentation of nodules on chest computed tomography for growth assessment

    International Nuclear Information System (INIS)

    Mullally, William; Betke, Margrit; Wang Jingbin; Ko, Jane P.

    2004-01-01

    Several segmentation methods to evaluate growth of small isolated pulmonary nodules on chest computed tomography (CT) are presented. The segmentation methods are based on adaptively thresholding attenuation levels and use measures of nodule shape. The segmentation methods were first tested on a realistic chest phantom to evaluate their performance with respect to specific nodule characteristics. The segmentation methods were also tested on sequential CT scans of patients. The methods' estimation of nodule growth were compared to the volume change calculated by a chest radiologist. The best method segmented nodules on average 43% smaller or larger than the actual nodule when errors were computed across all nodule variations on the phantom. Some methods achieved smaller errors when examined with respect to certain nodule properties. In particular, on the phantom individual methods segmented solid nodules to within 23% of their actual size and nodules with 60.7 mm3 volumes to within 14%. On the clinical data, none of the methods examined showed a statistically significant difference in growth estimation from the radiologist

  7. Segmentation of fluorescence microscopy cell images using unsupervised mining.

    Science.gov (United States)

    Du, Xian; Dua, Sumeet

    2010-05-28

    The accurate measurement of cell and nuclei contours are critical for the sensitive and specific detection of changes in normal cells in several medical informatics disciplines. Within microscopy, this task is facilitated using fluorescence cell stains, and segmentation is often the first step in such approaches. Due to the complex nature of cell issues and problems inherent to microscopy, unsupervised mining approaches of clustering can be incorporated in the segmentation of cells. In this study, we have developed and evaluated the performance of multiple unsupervised data mining techniques in cell image segmentation. We adapt four distinctive, yet complementary, methods for unsupervised learning, including those based on k-means clustering, EM, Otsu's threshold, and GMAC. Validation measures are defined, and the performance of the techniques is evaluated both quantitatively and qualitatively using synthetic and recently published real data. Experimental results demonstrate that k-means, Otsu's threshold, and GMAC perform similarly, and have more precise segmentation results than EM. We report that EM has higher recall values and lower precision results from under-segmentation due to its Gaussian model assumption. We also demonstrate that these methods need spatial information to segment complex real cell images with a high degree of efficacy, as expected in many medical informatics applications.

  8. Dialectical behavior therapy skills use and emotion dysregulation in personality disorders and psychopathy: a community self-report study.

    Science.gov (United States)

    Neacsiu, Andrada D; Tkachuck, Mathew A

    2016-01-01

    Emotion dysregulation is a critical transdiagnostic mental health problem that needs to be further examined in personality disorders (PDs). The current study examined dialectical behavior therapy (DBT) skills use, emotion dysregulation, and dysfunctional coping among adults who endorsed symptoms of cluster B PDs and psychopathy. We hypothesized that skills taught in DBT and emotion dysregulation are useful for adults with PDs other than borderline personality disorder (BPD). Using a self-report questionnaire, we examined these constructs in three groups of community adults: those who reported symptoms consistent with borderline personality disorder (BPD; N = 29), those who reported symptoms consistent with any other cluster B PD (N = 22), and those with no reported cluster B PD symptoms (N = 77) as measured by the Personality Diagnostic Questionnaire-4 + . Both PD groups reported higher emotion dysregulation and dysfunctional coping when compared to the no PD group. Only the BPD group had significantly lower DBT skills use. DBT skills use was found to be a significant predictor of cluster B psychopathology but only before accounting for emotion dysregulation. When added to the regression model, emotion dysregulation was found to be a significant predictor of cluster B psychopathology but DBT skills use no longer had a significant effect. Across all groups, DBT skills use deficits and maladaptive coping, but not emotion dysregulation, predicted different facets of psychopathy. Emotion dysregulation and use of maladaptive coping are problems in cluster B PDs, outside of BPD, but not in psychopathy. Inability to use DBT skills may be unique to BPD. Because this study relied exclusively on self-report, this data is preliminary and warrants further investigation.

  9. Dictionary Based Segmentation in Volumes

    DEFF Research Database (Denmark)

    Emerson, Monica Jane; Jespersen, Kristine Munk; Jørgensen, Peter Stanley

    Method for supervised segmentation of volumetric data. The method is trained from manual annotations, and these annotations make the method very flexible, which we demonstrate in our experiments. Our method infers label information locally by matching the pattern in a neighborhood around a voxel ...... to a dictionary, and hereby accounts for the volume texture....

  10. Multiple Segmentation of Image Stacks

    DEFF Research Database (Denmark)

    Smets, Jonathan; Jaeger, Manfred

    2014-01-01

    We propose a method for the simultaneous construction of multiple image segmentations by combining a recently proposed “convolution of mixtures of Gaussians” model with a multi-layer hidden Markov random field structure. The resulting method constructs for a single image several, alternative...

  11. Segmenting Trajectories by Movement States

    NARCIS (Netherlands)

    Buchin, M.; Kruckenberg, H.; Kölzsch, A.; Timpf, S.; Laube, P.

    2013-01-01

    Dividing movement trajectories according to different movement states of animals has become a challenge in movement ecology, as well as in algorithm development. In this study, we revisit and extend a framework for trajectory segmentation based on spatio-temporal criteria for this purpose. We adapt

  12. Segmental Colitis Complicating Diverticular Disease

    Directory of Open Access Journals (Sweden)

    Guido Ma Van Rosendaal

    1996-01-01

    Full Text Available Two cases of idiopathic colitis affecting the sigmoid colon in elderly patients with underlying diverticulosis are presented. Segmental resection has permitted close review of the histopathology in this syndrome which demonstrates considerable similarity to changes seen in idiopathic ulcerative colitis. The reported experience with this syndrome and its clinical features are reviewed.

  13. Leaf segmentation in plant phenotyping

    NARCIS (Netherlands)

    Scharr, Hanno; Minervini, Massimo; French, Andrew P.; Klukas, Christian; Kramer, David M.; Liu, Xiaoming; Luengo, Imanol; Pape, Jean Michel; Polder, Gerrit; Vukadinovic, Danijela; Yin, Xi; Tsaftaris, Sotirios A.

    2016-01-01

    Image-based plant phenotyping is a growing application area of computer vision in agriculture. A key task is the segmentation of all individual leaves in images. Here we focus on the most common rosette model plants, Arabidopsis and young tobacco. Although leaves do share appearance and shape

  14. Segmentation of urinary bladder in CT Urography (CTU) using CLASS

    Science.gov (United States)

    Hadjiiski, Lubomir; Chan, Heang-Ping; Law, Yuen; Cohan, Richard H.; Caoili, Elaine M.; Cho, Hyun-Chong; Zhou, Chuan; Wei, Jun

    2012-03-01

    We are developing a computerized system for bladder segmentation on CTU, as a critical component for computer aided diagnosis of bladder cancer. A challenge for bladder segmentation is the presence of regions without contrast (NC) and filled with IV contrast (C). We are developing a Conjoint Level set Analysis and Segmentation System (CLASS) specifically for this application. CLASS performs a series of image processing tasks: preprocessing, initial segmentation, and 3D and 2D level set segmentation and post-processing, designed according to the characteristics of the bladder in CTU. The NC and the C regions of the bladder were segmented separately in CLASS. The final contour is obtained in the post-processing stage by the union of the NC and C contours. Seventy bladders (31 containing lesions, 24 containing wall thickening, and 15 normal) were segmented. The performance of CLASS was assessed by rating the quality of the contours on a 5-point scale (1= "very poor", 3= "fair", 5 = "excellent"). For the 53 partially contrast-filled bladders, the average quality ratings for the 53 NC and 53 C regions were 4.0+/-0.7 and 4.0+/-1.0, respectively. 46 NC and 41 C regions were given quality ratings of 4 or above. Only 2 NC and 5 C regions had ratings under 3. The average quality ratings for the remaining 12 completely no contrast (NC) and 5 completely contrast-filled (C) bladder contours were 3.3+/-1.0 and 3.4+/-0.5, respectively. After combining the NC and C contours for each of the 70 bladders, 46 had quality ratings of 4 or above. Only 4 had ratings under 3. The average quality rating was 3.8+/-0.7. The results demonstrate the potential of CLASS for automated segmentation of the bladder.

  15. Frictionless segmented mechanics for controlled space closure.

    Science.gov (United States)

    Andrade, Ildeu

    2017-02-01

    Extraction spaces may be needed to achieve specific orthodontic goals of positioning the dentition in harmony with the craniofacial complex. However, the fundamental reality that determines the occlusion final position is the control exerted by the orthodontist while closing the extraction spaces. A specific treatment objective may require the posterior teeth to remain in a constant position anteroposteriorly as well as vertically, while the anterior teeth occupy the entire extraction site. Another treatment objective may require the opposite, or any number of intentional alternatives of extraction site closure. The present case report describes a simple controlled segmented mechanic system that permitted definable and predictable force systems to be applied and allowed to predict the treatment outcome with confidence. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO) in partial fulfillment of the requirements for Diplomate certification.

  16. Frictionless segmented mechanics for controlled space closure

    Directory of Open Access Journals (Sweden)

    Ildeu Andrade Jr

    Full Text Available ABSTRACT Extraction spaces may be needed to achieve specific orthodontic goals of positioning the dentition in harmony with the craniofacial complex. However, the fundamental reality that determines the occlusion final position is the control exerted by the orthodontist while closing the extraction spaces. A specific treatment objective may require the posterior teeth to remain in a constant position anteroposteriorly as well as vertically, while the anterior teeth occupy the entire extraction site. Another treatment objective may require the opposite, or any number of intentional alternatives of extraction site closure. The present case report describes a simple controlled segmented mechanic system that permitted definable and predictable force systems to be applied and allowed to predict the treatment outcome with confidence. This case was presented to the Brazilian Board of Orthodontics and Dentofacial Orthopedics (BBO in partial fulfillment of the requirements for Diplomate certification.

  17. Relations between segmental and motor variability in prosodically complex nonword sequences.

    Science.gov (United States)

    Goffman, Lisa; Gerken, Louann; Lucchesi, Julie

    2007-04-01

    To assess how prosodic prominence and hierarchical foot structure influence segmental and articulatory aspects of speech production, specifically segmental accuracy and variability, and oral movement trajectory variability. Thirty individuals participated: 10 young adults, 10 children who are normally developing, and 10 children diagnosed with specific language impairment. Segmental error and segmental variability and movement trajectory variability were compared in low and high prosodic prominence conditions (i.e., strong and weak syllables) and in different prosodic foot structures. Between-participants findings were that both groups of children showed more segmental error and segmental variability and more movement trajectory variability than did adults. A similar within-participant pattern of results was observed for all 3 groups. Prosodic prominence influenced both segmental and motor levels of analysis, with weak syllables produced less accurately and with more lip and jaw movement trajectory variability than strong syllables. However, hierarchical foot structure affected segmental but not motor measures of speech production accuracy and variability. Motor and segmental variables were not consistently aligned. This pattern of results has clinical implications because inferences about motor variability may not directly follow from observations of segmental variability.

  18. Joint shape segmentation with linear programming

    KAUST Repository

    Huang, Qixing

    2011-01-01

    We present an approach to segmenting shapes in a heterogenous shape database. Our approach segments the shapes jointly, utilizing features from multiple shapes to improve the segmentation of each. The approach is entirely unsupervised and is based on an integer quadratic programming formulation of the joint segmentation problem. The program optimizes over possible segmentations of individual shapes as well as over possible correspondences between segments from multiple shapes. The integer quadratic program is solved via a linear programming relaxation, using a block coordinate descent procedure that makes the optimization feasible for large databases. We evaluate the presented approach on the Princeton segmentation benchmark and show that joint shape segmentation significantly outperforms single-shape segmentation techniques. © 2011 ACM.

  19. Negative parental attribution and emotional dysregulation in Chinese early adolescents: Harsh fathering and harsh mothering as potential mediators.

    Science.gov (United States)

    Wang, Mingzhong; Wang, Jing

    2018-04-21

    The current study examined the potential mediating roles of harsh fathering and harsh mothering in the association between negative parental attribution and emotional dysregulation in Chinese adolescents and explored the moderating role of child gender on this indirect association. 864 students (367 girls, mean age = 13.55 years) with their parents were recruited as participants from two middle schools in Shandong Province, People's Republic of China. The results demonstrated that both harsh fathering and harsh mothering could partially mediate the association between negative maternal attribution and child emotional dysregulation, whereas only harsh fathering could partially mediate the association between negative paternal attribution and child emotional dysregulation. Moreover, we found the moderating role of child gender only for the association between harsh fathering and child emotional dysregulation, in that harsh fathering could be associated with higher levels of emotional dysregulation in girls. These results shed light on efforts to prevent harsh parenting and child emotional dysregulation. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. HealthStyles: a new psychographic segmentation system for health care marketers.

    Science.gov (United States)

    Endresen, K W; Wintz, J C

    1988-01-01

    HealthStyles is a new psychographic segmentation system specifically designed for the health care industry. This segmentation system goes beyond traditional geographic and demographic analysis and examines health-related consumer attitudes and behaviors. Four statistically distinct "styles" of consumer health care preferences have been identified. The profiles of the four groups have substantial marketing implications in terms of design and promotion of products and services. Each segment of consumers also has differing expectations of physician behavior.

  1. Affect dysregulation, psychoform dissociation, and adult relational fears mediate the relationship between childhood trauma and complex posttraumatic stress disorder independent of the symptoms of borderline personality disorder.

    Science.gov (United States)

    van Dijke, Annemiek; Hopman, Juliette A B; Ford, Julian D

    2018-01-01

    Objective : Complex posttraumatic stress disorder (CPTSD) as defined by the Disorders of Extreme Stress Not Otherwise Specified (DESNOS) formulation is associated with childhood relational trauma and involves relational impairment, affect dysregulation, and identity alterations. However, the distinct contributions of relational impairment (operationalized in the form fears of closeness or abandonment), affect dysregulation (operationalized in the form of overregulation and under-regulation of affect), and identity alterations (operationalized in the form of positive or negative psychoform or somatoform dissociation) to the relationship between childhood trauma and CPTSD/DESNOS have not been systematically tested. Method and Results : In a clinical sample of adults diagnosed with severe and chronic psychiatric and personality disorders ( n  = 472; M  = 34.7 years, SD  = 10.1), structural equation modelling with bootstrap 95% confidence intervals demonstrated that the association between childhood trauma and CPTSD/DESNOS symptoms in adulthood was partially mediated by under-regulation of affect, negative psychoform dissociation, and adult relational fears of closeness and of abandonment. These results also were independent of the effects of borderline personality disorder (BPD) symptoms. Conclusions : Some, but not all, hypothesized components of the DESNOS formulation of CPTSD statistically mediate the relationship between childhood trauma and adult CPTSD/DESNOS. These relationships appear specific to CPTSD/DESNOS and not to the effects of another potential sequelae of childhood trauma BPD. Replication with prospective longitudinal studies is needed.

  2. Stochastic Modelling as a Tool for Seismic Signals Segmentation

    Directory of Open Access Journals (Sweden)

    Daniel Kucharczyk

    2016-01-01

    Full Text Available In order to model nonstationary real-world processes one can find appropriate theoretical model with properties following the analyzed data. However in this case many trajectories of the analyzed process are required. Alternatively, one can extract parts of the signal that have homogenous structure via segmentation. The proper segmentation can lead to extraction of important features of analyzed phenomena that cannot be described without the segmentation. There is no one universal method that can be applied for all of the phenomena; thus novel methods should be invented for specific cases. They might address specific character of the signal in different domains (time, frequency, time-frequency, etc.. In this paper we propose two novel segmentation methods that take under consideration the stochastic properties of the analyzed signals in time domain. Our research is motivated by the analysis of vibration signals acquired in an underground mine. In such signals we observe seismic events which appear after the mining activity, like blasting, provoked relaxation of rock, and some unexpected events, like natural rock burst. The proposed segmentation procedures allow for extraction of such parts of the analyzed signals which are related to mentioned events.

  3. Identifying uniformly mutated segments within repeats.

    Science.gov (United States)

    Sahinalp, S Cenk; Eichler, Evan; Goldberg, Paul; Berenbrink, Petra; Friedetzky, Tom; Ergun, Funda

    2004-12-01

    Given a long string of characters from a constant size alphabet we present an algorithm to determine whether its characters have been generated by a single i.i.d. random source. More specifically, consider all possible n-coin models for generating a binary string S, where each bit of S is generated via an independent toss of one of the n coins in the model. The choice of which coin to toss is decided by a random walk on the set of coins where the probability of a coin change is much lower than the probability of using the same coin repeatedly. We present a procedure to evaluate the likelihood of a n-coin model for given S, subject a uniform prior distribution over the parameters of the model (that represent mutation rates and probabilities of copying events). In the absence of detailed prior knowledge of these parameters, the algorithm can be used to determine whether the a posteriori probability for n=1 is higher than for any other n>1. Our algorithm runs in time O(l4logl), where l is the length of S, through a dynamic programming approach which exploits the assumed convexity of the a posteriori probability for n. Our test can be used in the analysis of long alignments between pairs of genomic sequences in a number of ways. For example, functional regions in genome sequences exhibit much lower mutation rates than non-functional regions. Because our test provides means for determining variations in the mutation rate, it may be used to distinguish functional regions from non-functional ones. Another application is in determining whether two highly similar, thus evolutionarily related, genome segments are the result of a single copy event or of a complex series of copy events. This is particularly an issue in evolutionary studies of genome regions rich with repeat segments (especially tandemly repeated segments).

  4. FREQUENT SUBGRAPH MINING OF PERSONALIZED SIGNALING PATHWAY NETWORKS GROUPS PATIENTS WITH FREQUENTLY DYSREGULATED DISEASE PATHWAYS AND PREDICTS PROGNOSIS.

    Science.gov (United States)

    Durmaz, Arda; Henderson, Tim A D; Brubaker, Douglas; Bebek, Gurkan

    2017-01-01

    Large scale genomics studies have generated comprehensive molecular characterization of numerous cancer types. Subtypes for many tumor types have been established; however, these classifications are based on molecular characteristics of a small gene sets with limited power to detect dysregulation at the patient level. We hypothesize that frequent graph mining of pathways to gather pathways functionally relevant to tumors can characterize tumor types and provide opportunities for personalized therapies. In this study we present an integrative omics approach to group patients based on their altered pathway characteristics and show prognostic differences within breast cancer (p network-based classifier algorithms and showed that our unsupervised approach generates more robust and biologically relevant clustering whereas previous approaches failed to report specific functions for similar patient groups or classify patients into prognostic groups. These results could serve as a means to improve prognosis for future cancer patients, and to provide opportunities for improved treatment options and personalized interventions. The proposed novel graph mining approach is able to integrate PPI networks with gene expression in a biologically sound approach and cluster patients in to clinically distinct groups. We have utilized breast cancer and glioblastoma multiforme datasets from microarray and RNA-Seq platforms and identified disease mechanisms differentiating samples. Supplementary methods, figures, tables and code are available at https://github.com/bebeklab/dysprog.

  5. Myeloid Dysregulation in a Human Induced Pluripotent Stem Cell Model of PTPN11-Associated Juvenile Myelomonocytic Leukemia

    Directory of Open Access Journals (Sweden)

    Sonia Mulero-Navarro

    2015-10-01

    Full Text Available Somatic PTPN11 mutations cause juvenile myelomonocytic leukemia (JMML. Germline PTPN11 defects cause Noonan syndrome (NS, and specific inherited mutations cause NS/JMML. Here, we report that hematopoietic cells differentiated from human induced pluripotent stem cells (hiPSCs harboring NS/JMML-causing PTPN11 mutations recapitulated JMML features. hiPSC-derived NS/JMML myeloid cells exhibited increased signaling through STAT5 and upregulation of miR-223 and miR-15a. Similarly, miR-223 and miR-15a were upregulated in 11/19 JMML bone marrow mononuclear cells harboring PTPN11 mutations, but not those without PTPN11 defects. Reducing miR-223’s function in NS/JMML hiPSCs normalized myelogenesis. MicroRNA target gene expression levels were reduced in hiPSC-derived myeloid cells as well as in JMML cells with PTPN11 mutations. Thus, studying an inherited human cancer syndrome with hiPSCs illuminated early oncogenesis prior to the accumulation of secondary genomic alterations, enabling us to discover microRNA dysregulation, establishing a genotype-phenotype association for JMML and providing therapeutic targets.

  6. Transcriptional differences between normal and glioma-derived glial progenitor cells identify a core set of dysregulated genes.

    Science.gov (United States)

    Auvergne, Romane M; Sim, Fraser J; Wang, Su; Chandler-Militello, Devin; Burch, Jaclyn; Al Fanek, Yazan; Davis, Danielle; Benraiss, Abdellatif; Walter, Kevin; Achanta, Pragathi; Johnson, Mahlon; Quinones-Hinojosa, Alfredo; Natesan, Sridaran; Ford, Heide L; Goldman, Steven A

    2013-06-27

    Glial progenitor cells (GPCs) are a potential source of malignant gliomas. We used A2B5-based sorting to extract tumorigenic GPCs from human gliomas spanning World Health Organization grades II-IV. Messenger RNA profiling identified a cohort of genes that distinguished A2B5+ glioma tumor progenitor cells (TPCs) from A2B5+ GPCs isolated from normal white matter. A core set of genes and pathways was substantially dysregulated in A2B5+ TPCs, which included the transcription factor SIX1 and its principal cofactors, EYA1 and DACH2. Small hairpin RNAi silencing of SIX1 inhibited the expansion of glioma TPCs in vitro and in vivo, suggesting a critical and unrecognized role of the SIX1-EYA1-DACH2 system in glioma genesis or progression. By comparing the expression patterns of glioma TPCs with those of normal GPCs, we have identified a discrete set of pathways by which glial tumorigenesis may be better understood and more specifically targeted. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  7. The herpes simplex virus-induced demise of keratinocytes is associated with a dysregulated pattern of p63 expression.

    Science.gov (United States)

    Megyeri, Klára; Orosz, László; Kormos, Bernadett; Pásztor, Katalin; Seprényi, György; Ocsovszki, Imre; Mándi, Yvette; Bata-Csörgo, Zsuzsanna; Kemény, Lajos

    2009-01-01

    p63 plays a pivotal role in the development and maintenance of stratified epithelial tissues. In an effort to gain insight into the pathogenic mechanisms of skin infections caused by HSV-1 and HSV-2, we determined the patterns of p63 expression in primary keratinocytes and in the HaCaT cell line. The levels of DeltaNp63alpha and a 50kDa p73 isoform were decreased, Bax-alpha remained unaffected, while the expressions of the Bax-beta, TAp63gamma and a 44.5kDa p73 isoform were highly increased in both HSV-1-infected HaCaT cells and primary keratinocytes. In contrast, in response to HSV-2 infection the levels of DeltaNp63alpha, a 50kDa p73 isoform and a 44.5kDa p73 protein were decreased, Bax-alpha and TAp63gamma remained unaffected, while the expression of Bax-beta was slightly increased. The knockdown of TAp63 expression enhanced the viability of HSV-1-infected cells. Thus, HSV-1 and HSV-2 modulate the patterns of p63 and Bax expression in a serotype-specific manner. The dysregulated pattern of p63 expression observed in HSV-infected keratinocytes may comprise part of a mechanism by which these viruses perturb the functions of keratinocytes and lead to their demise.

  8. Novel Music Segmentation Interface and the Jazz Tune Collection

    NARCIS (Netherlands)

    Rodríguez López, M.E.; Bountouridis, D.; Volk, A.

    2015-01-01

    In this paper we present MOSSA, an easy-to-use interface for mobile devices, developed to annotate the segment structure of music. Moreover, we present the jazz tune collection (JTC), a database of 125 Jazz melodies annotated using MOSSA, and developed specifically for benchmarking of computational

  9. Elephant: Sequence Labeling for Word and Sentence Segmentation

    NARCIS (Netherlands)

    Evang, Kilian; Basile, Valerio; Chrupala, Grzegorz; Bos, Johan

    2013-01-01

    Tokenization is widely regarded as a solved problem due to the high accuracy that rule-based tokenizers achieve. But rule-based tokenizers are hard to maintain and their rules language specific. We show that high-accuracy word and sentence segmentation can be achieved by using supervised sequence

  10. Targeting Political Communications: A Problem in Market Segmentation.

    Science.gov (United States)

    Markwart, Richard I.

    Political campaigns are major, high-budget marketing efforts, but because they are usually managed by people with little training in either marketing or communications, they fail to persuade voters to vote in the desired way. Political targeting can be treated as a segmentation problem, one of identifying and responding to the specific qualities…

  11. Dictionary Based Segmentation in Volumes

    DEFF Research Database (Denmark)

    Emerson, Monica Jane; Jespersen, Kristine Munk; Jørgensen, Peter Stanley

    2015-01-01

    We present a method for supervised volumetric segmentation based on a dictionary of small cubes composed of pairs of intensity and label cubes. Intensity cubes are small image volumes where each voxel contains an image intensity. Label cubes are volumes with voxelwise probabilities for a given...... label. The segmentation process is done by matching a cube from the volume, of the same size as the dictionary intensity cubes, to the most similar intensity dictionary cube, and from the associated label cube we get voxel-wise label probabilities. Probabilities from overlapping cubes are averaged...... and hereby we obtain a robust label probability encoding. The dictionary is computed from labeled volumetric image data based on weighted clustering. We experimentally demonstrate our method using two data sets from material science – a phantom data set of a solid oxide fuel cell simulation for detecting...

  12. Compliance with Segment Disclosure Initiatives

    DEFF Research Database (Denmark)

    Arya, Anil; Frimor, Hans; Mittendorf, Brian

    2013-01-01

    Regulatory oversight of capital markets has intensified in recent years, with a particular emphasis on expanding financial transparency. A notable instance is efforts by the Financial Accounting Standards Board that push firms to identify and report performance of individual business units...... (segments). This paper seeks to address short-run and long-run consequences of stringent enforcement of and uniform compliance with these segment disclosure standards. To do so, we develop a parsimonious model wherein a regulatory agency promulgates disclosure standards and either permits voluntary...... by increasing transparency and leveling the playing field. However, our analysis also demonstrates that in the long run, if firms are unable to use discretion in reporting to maintain their competitive edge, they may seek more destructive alternatives. Accounting for such concerns, in the long run, voluntary...

  13. Segmental osteotomies of the maxilla.

    Science.gov (United States)

    Rosen, H M

    1989-10-01

    Multiple segment Le Fort I osteotomies provide the maxillofacial surgeon with the capabilities to treat complex dentofacial deformities existing in all three planes of space. Sagittal, vertical, and transverse maxillomandibular discrepancies as well as three-dimensional abnormalities within the maxillary arch can be corrected simultaneously. Accordingly, optimal aesthetic enhancement of the facial skeleton and a functional, healthy occlusion can be realized. What may be perceived as elaborate treatment plans are in reality conservative in terms of osseous stability and treatment time required. The close cooperation of an orthodontist well-versed in segmental orthodontics and orthognathic surgery is critical to the success of such surgery. With close attention to surgical detail, the complication rate inherent in such surgery can be minimized and the treatment goals achieved in a timely and predictable fashion.

  14. Segmented fuel and moderator rod

    International Nuclear Information System (INIS)

    Doshi, P.K.

    1987-01-01

    This patent describes a continuous segmented fuel and moderator rod for use with a water cooled and moderated nuclear fuel assembly. The rod comprises: a lower fuel region containing a column of nuclear fuel; a moderator region, disposed axially above the fuel region. The moderator region has means for admitting and passing the water moderator therethrough for moderating an upper portion of the nuclear fuel assembly. The moderator region is separated from the fuel region by a water tight separator

  15. Segmentation of sows in farrowing pens

    DEFF Research Database (Denmark)

    Tu, Gang Jun; Karstoft, Henrik; Pedersen, Lene Juul

    2014-01-01

    The correct segmentation of a foreground object in video recordings is an important task for many surveillance systems. The development of an effective and practical algorithm to segment sows in grayscale video recordings captured under commercial production conditions is described...

  16. The strategic marketing planning – General Framework for Customer Segmentation

    Directory of Open Access Journals (Sweden)

    Alina Elena OPRESCU

    2014-03-01

    Full Text Available Any approach that involves the use of strategic resources of an organisation requires a responsible approach, a behaviour that enables it to properly integrate itself into the dynamic of the business environment. This articles addresses in a synthetic manner, the issues of specific integration efforts for customers’ segmentation in the strategic marketing planning. The essential activity for any organisation wishing to optimise its response to the market, the customer segmentation will fully benefit from the framework provided by the strategic marketing planning. Being a sequential process, it not only allows time optimisation of the entire marketing activity but it also leads to accuracy of the strategic planning and its stages.

  17. Segmentation in local hospital markets.

    Science.gov (United States)

    Dranove, D; White, W D; Wu, L

    1993-01-01

    This study examines evidence of market segmentation on the basis of patients' insurance status, demographic characteristics, and medical condition in selected local markets in California in the years 1983 and 1989. Substantial differences exist in the probability patients may be admitted to particular hospitals based on insurance coverage, particularly Medicaid, and race. Segmentation based on insurance and race is related to hospital characteristics, but not the characteristics of the hospital's community. Medicaid patients are more likely to go to hospitals with lower costs and fewer service offerings. Privately insured patients go to hospitals offering more services, although cost concerns are increasing. Hispanic patients also go to low-cost hospitals, ceteris paribus. Results indicate little evidence of segmentation based on medical condition in either 1983 or 1989, suggesting that "centers of excellence" have yet to play an important role in patient choice of hospital. The authors found that distance matters, and that patients prefer nearby hospitals, moreso for some medical conditions than others, in ways consistent with economic theories of consumer choice.

  18. Dysregulation of mitotic machinery genes precedes genome instability during spontaneous pre-malignant transformation of mouse ovarian surface epithelial cells

    Directory of Open Access Journals (Sweden)

    Ulises Urzúa

    2016-10-01

    Full Text Available Abstract Background Based in epidemiological evidence, repetitive ovulation has been proposed to play a role in the origin of ovarian cancer by inducing an aberrant wound rupture-repair process of the ovarian surface epithelium (OSE. Accordingly, long term cultures of isolated OSE cells undergo in vitro spontaneous transformation thus developing tumorigenic capacity upon extensive subcultivation. In this work, C57BL/6 mouse OSE (MOSE cells were cultured up to passage 28 and their RNA and DNA copy number profiles obtained at passages 2, 5, 7, 10, 14, 18, 23, 25 and 28 by means of DNA microarrays. Gene ontology, pathway and network analyses were focused in passages earlier than 20, which is a hallmark of malignancy in this model. Results At passage 14, 101 genes were up-regulated in absence of significant DNA copy number changes. Among these, the top-3 enriched functions (>30 fold, adj p < 0.05 comprised 7 genes coding for centralspindlin, chromosome passenger and minichromosome maintenance protein complexes. The genes Ccnb1 (Cyclin B1, Birc5 (Survivin, Nusap1 and Kif23 were the most recurrent in over a dozen GO terms related to the mitotic process. On the other hand, Pten plus the large non-coding RNAs Malat1 and Neat1 were among the 80 down-regulated genes with mRNA processing, nuclear bodies, ER-stress response and tumor suppression as relevant terms. Interestingly, the earliest discrete segmental aneuploidies arose by passage 18 in chromosomes 7, 10, 11, 13, 15, 17 and 19. By passage 23, when MOSE cells express the malignant phenotype, the dysregulated gene expression repertoire expanded, DNA imbalances enlarged in size and covered additional loci. Conclusion Prior to early aneuploidies, overexpression of genes coding for the mitotic apparatus in passage-14 pre-malignant MOSE cells indicate an increased proliferation rate suggestive of replicative stress. Concomitant down-regulation of nuclear bodies and RNA processing related genes

  19. Understanding the market for geographic information: A market segmentation and characteristics analysis

    Science.gov (United States)

    Piper, William S.; Mick, Mark W.

    1994-01-01

    Findings and results from a marketing research study are presented. The report identifies market segments and the product types to satisfy demand in each. An estimate of market size is based on the specific industries in each segment. A sample of ten industries was used in the study. The scientific study covered U.S. firms only.

  20. Roentgenological diagnoss of central segmental lung cancer

    International Nuclear Information System (INIS)

    Gurevich, L.A.; Fedchenko, G.G.

    1984-01-01

    Basing on an analysis of the results of clinicoroentgenological examination of 268 patments roentgenological semiotics of segmental lung cancer is presented. Some peculiarities of the X-ray picture of cancer of different segments of the lungs were revealed depending on tumor site and growth type. For the syndrome of segmental darkening the comprehensive X-ray methods where the chief method is tomography of the segmental bronchi are proposed

  1. Review of segmentation process in consumer markets

    OpenAIRE

    Veronika Jadczaková

    2013-01-01

    Although there has been a considerable debate on market segmentation over five decades, attention was merely devoted to single stages of the segmentation process. In doing so, stages as segmentation base selection or segments profiling have been heavily covered in the extant literature, whereas stages as implementation of the marketing strategy or market definition were of a comparably lower interest. Capitalizing on this shortcoming, this paper strives to close the gap and provide each step...

  2. Dysregulated left inferior parietal activity in schizophrenia and depression: functional connectivity and characterization

    Directory of Open Access Journals (Sweden)

    Veronika I. Müller

    2013-06-01

    Full Text Available The inferior parietal cortex (IPC is a heterogeneous region that is known to be involved in a multitude of diverse different tasks and processes, though its contribution to these often-complex functions is yet poorly understood. In a previous study we demonstrated that patients with depression failed to deactivate the left IPC during processing of congruent audiovisual information. We now found the same dysregulation (same region and condition in schizophrenia. By using task-independent (resting state and task-dependent (MACM analyses we aimed at characterizing this particular region with regard to its connectivity and function. Across both approaches, results revealed functional connectivity of the left inferior parietal seed region with bilateral IPC, precuneus and posterior cingulate cortex (PrC/PCC, medial orbitofrontal cortex (mOFC, left middle frontal (MFG as well as inferior frontal (IFG gyrus. Network-level functional characterization further revealed that on the one hand, all interconnected regions are part of a network involved in memory processes. On the other hand, sub-networks are formed when emotion, language, social cognition and reasoning processes are required. Thus, the IPC-region that is dysregulated in both depression and schizophrenia is functionally connected to a network of regions which, depending on task demands may form sub-networks. These results therefore indicate that dysregulation of left IPC in depression and schizophrenia might not only be connected to deficits in audiovisual integration, but is possibly also associated to impaired memory and deficits in emotion processing in these patient groups.

  3. Dysregulation of chemokine receptor expression and function in leukocytes from ALS patients.

    Science.gov (United States)

    Perner, Caroline; Perner, Florian; Stubendorff, Beatrice; Förster, Martin; Witte, Otto W; Heidel, Florian H; Prell, Tino; Grosskreutz, Julian

    2018-03-28

    Amyotrophic lateral sclerosis (ALS) is rapidly progressive adult-onset motor neuron disease characterized by the neurodegeneration of both upper and lower motor neurons in the cortex and the spinal cord; the majority of patients succumb to respiratory failure. Although the etiology is not yet fully understood, there is compelling evidence that ALS is a multi-systemic disorder, with peripheral inflammation critically contributing to the disease process. However, the full extent and nature of this immunological dysregulation remains to be established, particularly within circulating blood cells. Therefore, the aim of the present study was to identify dysregulated inflammatory molecules in peripheral blood cells of ALS patients and analyze for functional consequences of the observed findings. To this end, we employed flow cytometry-based screening to quantify the surface expression of major chemokine receptors and integrins. A significantly increased expression of CXCR3, CXCR4, CCL2, and CCL5 was observed on T cells in ALS patients compared to healthy controls. Intriguingly, the expression was even more pronounced in patients with a slow progressive phenotype. To further investigate the functional consequences of this altered surface expression, we used a modified Boyden chamber assay to measure chemotaxis in ALS patient-derived lymphocytes. Interestingly, chemoattraction with the CXCR3-Ligand IP10 led to upregulated migratory behavior of ALS lymphocytes compared to healthy controls. Taken together, our data provides evidence for a functional dysregulation of IP10-directed chemotaxis in peripheral blood cells in ALS patients. However, whether the chemokine itself or its receptor CXCR3, or both, could serve as potential therapeutic targets in ALS requires further investigations.

  4. Topology and robustness in the Drosophila segment polarity network.

    Directory of Open Access Journals (Sweden)

    Nicholas T Ingolia

    2004-06-01

    Full Text Available A complex hierarchy of genetic interactions converts a single-celled Drosophila melanogaster egg into a multicellular embryo with 14 segments. Previously, von Dassow et al. reported that a mathematical model of the genetic interactions that defined the polarity of segments (the segment polarity network was robust (von Dassow et al. 2000. As quantitative information about the system was unavailable, parameters were sampled randomly. A surprisingly large fraction of these parameter sets allowed the model to maintain and elaborate on the segment polarity pattern. This robustness is due to the positive feedback of gene products on their own expression, which induces individual cells in a model segment to adopt different stable expression states (bistability corresponding to different cell types in the segment polarity pattern. A positive feedback loop will only yield multiple stable states when the parameters that describe it satisfy a particular inequality. By testing which random parameter sets satisfy these inequalities, I show that bistability is necessary to form the segment polarity pattern and serves as a strong predictor of which parameter sets will succeed in forming the pattern. Although the original model was robust to parameter variation, it could not reproduce the observed effects of cell division on the pattern of gene expression. I present a modified version that incorporates recent experimental evidence and does successfully mimic the consequences of cell division. The behavior of this modified model can also be understood in terms of bistability in positive feedback of gene expression. I discuss how this topological property of networks provides robust pattern formation and how large changes in parameters can change the specific pattern produced by a network.

  5. Market Segmentation from a Behavioral Perspective

    Science.gov (United States)

    Wells, Victoria K.; Chang, Shing Wan; Oliveira-Castro, Jorge; Pallister, John

    2010-01-01

    A segmentation approach is presented using both traditional demographic segmentation bases (age, social class/occupation, and working status) and a segmentation by benefits sought. The benefits sought in this case are utilitarian and informational reinforcement, variables developed from the Behavioral Perspective Model (BPM). Using data from 1,847…

  6. Parallel fuzzy connected image segmentation on GPU

    OpenAIRE

    Zhuge, Ying; Cao, Yong; Udupa, Jayaram K.; Miller, Robert W.

    2011-01-01

    Purpose: Image segmentation techniques using fuzzy connectedness (FC) principles have shown their effectiveness in segmenting a variety of objects in several large applications. However, one challenge in these algorithms has been their excessive computational requirements when processing large image datasets. Nowadays, commodity graphics hardware provides a highly parallel computing environment. In this paper, the authors present a parallel fuzzy connected image segmentation algorithm impleme...

  7. LIFE-STYLE SEGMENTATION WITH TAILORED INTERVIEWING

    NARCIS (Netherlands)

    KAMAKURA, WA; WEDEL, M

    The authors present a tailored interviewing procedure for life-style segmentation. The procedure assumes that a life-style measurement instrument has been designed. A classification of a sample of consumers into life-style segments is obtained using a latent-class model. With these segments, the

  8. The Process of Marketing Segmentation Strategy Selection

    OpenAIRE

    Ionel Dumitru

    2007-01-01

    The process of marketing segmentation strategy selection represents the essence of strategical marketing. We present hereinafter the main forms of the marketing statategy segmentation: undifferentiated marketing, differentiated marketing, concentrated marketing and personalized marketing. In practice, the companies use a mix of these marketing segmentation methods in order to maximize the proffit and to satisfy the consumers’ needs.

  9. Early life adversity potentiates the effects of later life stress on cumulative physiological dysregulation

    DEFF Research Database (Denmark)

    Dich, Nadya; Hansen, Åse Marie; Avlund, Kirsten

    2015-01-01

    tested this hypothesis by investigating whether experience of stressful events and circumstances (SEC) in childhood or adolescence amplified the effect of adulthood SEC on physiological dysregulation (allostatic load, AL) in later midlife. Design: Observational data were used in the present study....... Physiological functioning was measured in later midlife (participants' age ranged from 49 to 63). Both childhood/adolescence and adulthood SEC were reported retrospectively on the same occasion. Methods: Participants were 5,309 Danish men and women from Copenhagen Ageing and Midlife Biobank. SEC included socio......: The results provide further insight into the mechanisms behind the "biological embedding" of childhood stress....

  10. Metabogenic and Nutriceutical Approaches to Address Energy Dysregulation and Skeletal Muscle Wasting in Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Emma Rybalka

    2015-11-01

    Full Text Available Duchenne Muscular Dystrophy (DMD is a fatal genetic muscle wasting disease with no current cure. A prominent, yet poorly treated feature of dystrophic muscle is the dysregulation of energy homeostasis which may be associated with intrinsic defects in key energy systems and promote muscle wasting. As such, supplementative nutriceuticals that target and augment the bioenergetical expansion of the metabolic pathways involved in cellular energy production have been widely investigated for their therapeutic efficacy in the treatment of DMD. We describe the metabolic nuances of dystrophin-deficient skeletal muscle and review the potential of various metabogenic and nutriceutical compounds to ameliorate the pathological and clinical progression of the disease.

  11. Segmentation of radiologic images with self-organizing maps: the segmentation problem transformed into a classification task

    Science.gov (United States)

    Pelikan, Erich; Vogelsang, Frank; Tolxdorff, Thomas

    1996-04-01

    The texture-based segmentation of x-ray images of focal bone lesions using topological maps is introduced. Texture characteristics are described by image-point correlation of feature images to feature vectors. For the segmentation, the topological map is labeled using an improved labeling strategy. Results of the technique are demonstrated on original and synthetic x-ray images and quantified with the aid of quality measures. In addition, a classifier-specific contribution analysis is applied for assessing the feature space.

  12. Automatic segmentation of mandible in panoramic x-ray.

    Science.gov (United States)

    Abdi, Amir Hossein; Kasaei, Shohreh; Mehdizadeh, Mojdeh

    2015-10-01

    As the panoramic x-ray is the most common extraoral radiography in dentistry, segmentation of its anatomical structures facilitates diagnosis and registration of dental records. This study presents a fast and accurate method for automatic segmentation of mandible in panoramic x-rays. In the proposed four-step algorithm, a superior border is extracted through horizontal integral projections. A modified Canny edge detector accompanied by morphological operators extracts the inferior border of the mandible body. The exterior borders of ramuses are extracted through a contour tracing method based on the average model of mandible. The best-matched template is fetched from the atlas of mandibles to complete the contour of left and right processes. The algorithm was tested on a set of 95 panoramic x-rays. Evaluating the results against manual segmentations of three expert dentists showed that the method is robust. It achieved an average performance of [Formula: see text] in Dice similarity, specificity, and sensitivity.

  13. Japanese migration in contemporary Japan: economic segmentation and interprefectural migration.

    Science.gov (United States)

    Fukurai, H

    1991-01-01

    This paper examines the economic segmentation model in explaining 1985-86 Japanese interregional migration. The analysis takes advantage of statistical graphic techniques to illustrate the following substantive issues of interregional migration: (1) to examine whether economic segmentation significantly influences Japanese regional migration and (2) to explain socioeconomic characteristics of prefectures for both in- and out-migration. Analytic techniques include a latent structural equation (LISREL) methodology and statistical residual mapping. The residual dispersion patterns, for instance, suggest the extent to which socioeconomic and geopolitical variables explain migration differences by showing unique clusters of unexplained residuals. The analysis further points out that extraneous factors such as high residential land values, significant commuting populations, and regional-specific cultures and traditions need to be incorporated in the economic segmentation model in order to assess the extent of the model's reliability in explaining the pattern of interprefectural migration.

  14. Polarization image segmentation of radiofrequency ablated porcine myocardial tissue.

    Directory of Open Access Journals (Sweden)

    Iftikhar Ahmad

    Full Text Available Optical polarimetry has previously imaged the spatial extent of a typical radiofrequency ablated (RFA lesion in myocardial tissue, exhibiting significantly lower total depolarization at the necrotic core compared to healthy tissue, and intermediate values at the RFA rim region. Here, total depolarization in ablated myocardium was used to segment the total depolarization image into three (core, rim and healthy zones. A local fuzzy thresholding algorithm was used for this multi-region segmentation, and then compared with a ground truth segmentation obtained from manual demarcation of RFA core and rim regions on the histopathology image. Quantitative comparison of the algorithm segmentation results was performed with evaluation metrics such as dice similarity coefficient (DSC = 0.78 ± 0.02 and 0.80 ± 0.02, sensitivity (Sn = 0.83 ± 0.10 and 0.91 ± 0.08, specificity (Sp = 0.76 ± 0.17 and 0.72 ± 0.17 and accuracy (Acc = 0.81 ± 0.09 and 0.71 ± 0.10 for RFA core and rim regions, respectively. This automatic segmentation of parametric depolarization images suggests a novel application of optical polarimetry, namely its use in objective RFA image quantification.

  15. Out of Warburg effect: An effective cancer treatment targeting the tumor specific metabolism and dysregulated pH.

    Science.gov (United States)

    Schwartz, Laurent; Seyfried, Thomas; Alfarouk, Khalid O; Da Veiga Moreira, Jorgelindo; Fais, Stefano

    2017-04-01

    As stated by Otto Warburg nearly a century ago, cancer is a metabolic disease, a fermentation caused by malfunctioning mitochondria, resulting in increased anabolism and decreased catabolism. Treatment should, therefore, aim at restoring the energy yield. To decrease anabolism, glucose uptake should be reduced (ketogenic diet). To increase catabolism, the oxidative phosphorylation should be restored. Treatment with a combination of α-lipoic acid and hydroxycitrate has been shown to be effective in multiple animal models. This treatment, in combination with conventional chemotherapy, has yielded extremely encouraging results in glioblastoma, brain metastasis and lung cancer. Randomized trials are necessary to confirm these preliminary data. The major limitation is the fact that the combination of α-lipoic acid and hydroxycitrate can only be effective if the mitochondria are still present and/or functional. That may not be the case in the most aggressive tumors. The increased intracellular alkalosis is a strong mitogenic signal, which bypasses most inhibitory signals. Concomitant correction of this alkalosis may be a very effective treatment in case of mitochondrial failure. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Aetiological pathways to Borderline Personality Disorder symptoms in early adolescence: childhood dysregulated behaviour, maladaptive parenting and bully victimisation.

    Science.gov (United States)

    Winsper, Catherine; Hall, James; Strauss, Vicky Y; Wolke, Dieter

    2017-01-01

    Developmental theories for the aetiology of Borderline Personality Disorder (BPD) suggest that both individual features (e.g., childhood dysregulated behaviour) and negative environmental experiences (e.g., maladaptive parenting, peer victimisation) may lead to the development of BPD symptoms during adolescence. Few prospective studies have examined potential aetiological pathways involving these two factors. We addressed this gap in the literature using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). We assessed mother-reported childhood dysregulated behaviour at 4, 7 and 8 years using the Strengths and Difficulties Questionnaire (SDQ); maladaptive parenting (maternal hitting, punishment, and hostility) at 8 to 9 years; and bully victimisation (child and mother report) at 8, 9 and 10 years. BPD symptoms were assessed at 11 years using the UK Childhood Interview for DSM-IV BPD. Control variables included adolescent depression (assessed with the Short Moods and Feelings Questionnaire-SMFQ) and psychotic symptoms (assessed with the Psychosis-Like Symptoms Interview-PLIKS) at 11 to 14 years, and mother's exposure to family adversity during pregnancy (assessed with the Family Adversity Scale-FAI). In unadjusted logistic regression analyses, childhood dysregulated behaviour and all environmental risk factors (i.e., family adversity, maladaptive parenting, and bully victimisation) were significantly associated with BPD symptoms at 11 years. Within structural equation modelling controlling for all associations simultaneously, family adversity and male sex significantly predicted dysregulated behaviour across childhood, while bully victimisation significantly predicted BPD, depression, and psychotic symptoms. Children displaying dysregulated behaviour across childhood were significantly more likely to experience maladaptive parenting (β = 0.075, p  bullying (β = 0.097, p  < 0.001). While significant indirect associations

  17. Segmentation Scheme for Safety Enhancement of Engineered Safety Features Component Control System

    International Nuclear Information System (INIS)

    Lee, Sangseok; Sohn, Kwangyoung; Lee, Junku; Park, Geunok

    2013-01-01

    Common Caused Failure (CCF) or undetectable failure would adversely impact safety functions of ESF-CCS in the existing nuclear power plants. We propose the segmentation scheme to solve these problems. Main function assignment to segments in the proposed segmentation scheme is based on functional dependency and critical function success path by using the dependency depth matrix. The segment has functional independence and physical isolation. The segmentation structure is that prohibit failure propagation to others from undetectable failures. Therefore, the segmentation system structure has robustness to undetectable failures. The segmentation system structure has functional diversity. The specific function in the segment defected by CCF, the specific function could be maintained by diverse control function that assigned to other segments. Device level control signals and system level control signals are separated and also control signal and status signals are separated due to signal transmission paths are allocated independently based on signal type. In this kind of design, single device failure or failures on signal path in the channel couldn't result in the loss of all segmented functions simultaneously. Thus the proposed segmentation function is the design scheme that improves availability of safety functions. In conventional ESF-CCS, the single controller generates the signal to control the multiple safety functions, and the reliability is achieved by multiplication within the channel. This design has a drawback causing the loss of multiple functions due to the CCF (Common Cause Failure) and single failure Heterogeneous controller guarantees the diversity ensuring the execution of safety functions against the CCF and single failure, but requiring a lot of resources like manpower and cost. The segmentation technology based on the compartmentalization and functional diversification decreases the CCF and single failure nonetheless the identical types of controllers

  18. Segmentation Scheme for Safety Enhancement of Engineered Safety Features Component Control System

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sangseok; Sohn, Kwangyoung [Korea Reliability Technology and System, Daejeon (Korea, Republic of); Lee, Junku; Park, Geunok [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2013-05-15

    Common Caused Failure (CCF) or undetectable failure would adversely impact safety functions of ESF-CCS in the existing nuclear power plants. We propose the segmentation scheme to solve these problems. Main function assignment to segments in the proposed segmentation scheme is based on functional dependency and critical function success path by using the dependency depth matrix. The segment has functional independence and physical isolation. The segmentation structure is that prohibit failure propagation to others from undetectable failures. Therefore, the segmentation system structure has robustness to undetectable failures. The segmentation system structure has functional diversity. The specific function in the segment defected by CCF, the specific function could be maintained by diverse control function that assigned to other segments. Device level control signals and system level control signals are separated and also control signal and status signals are separated due to signal transmission paths are allocated independently based on signal type. In this kind of design, single device failure or failures on signal path in the channel couldn't result in the loss of all segmented functions simultaneously. Thus the proposed segmentation function is the design scheme that improves availability of safety functions. In conventional ESF-CCS, the single controller generates the signal to control the multiple safety functions, and the reliability is achieved by multiplication within the channel. This design has a drawback causing the loss of multiple functions due to the CCF (Common Cause Failure) and single failure Heterogeneous controller guarantees the diversity ensuring the execution of safety functions against the CCF and single failure, but requiring a lot of resources like manpower and cost. The segmentation technology based on the compartmentalization and functional diversification decreases the CCF and single failure nonetheless the identical types of

  19. Distrustful, Conventional, Entitled, and Dysregulated: PID-5 Personality Facets Predict Hostile Masculinity and Sexual Violence in Community Men.

    Science.gov (United States)

    Russell, Tiffany D; King, Alan R

    2017-01-01

    Psychopathy and narcissism are known predictors of sexual violence, but they are broad personality constructs with limited utility in intervention and prevention efforts. The Personality Inventory for DSM-5 (PID-5) assesses 25 specific personality facets residing in five higher order domains. The goal of this research was to test the PID-5 in a sexual aggression model, which also included hostile masculinity, juvenile delinquency, and five sexual assault indices. A nationwide sample of adult men ( N = 512) completed the online survey. Hostile masculinity and juvenile delinquency were expected to have direct paths to sexual violence in a structural equation model. Hostile masculinity was also hypothesized as a mediator between sexual violence and PID-5 facets related to narcissism and psychopathy. These hypotheses were largely supported. Overall, 29.5% of men reported perpetrating sexual violence at least once, and 24.2% reported multiple assaults. In the sexually violent sample, 45.7% endorsed completed rape as their most severe act. PID-5 Suspiciousness, Cognitive and Perceptual Dysregulation, Grandiosity, and a lack of Eccentricity emerged as indirect predictors of sexual violence. These PID-5 facets were mediated by hostile masculinity, which had a reliable path to sexual violence. Juvenile delinquency had a direct and indirect path to sexual assault. The model accounted for 48% of the variance in latent sexual violence, and the five sexual violence index R 2 s ranged from .53 to .82. This research adds specificity to sexual violence models by demonstrating the underlying maladaptive personality trait structures associated with sexual assault. It also provides a more precise personality profile for clinical use and prevention programs.

  20. Delineating the psychic structure of substance abuse and addictions: should anxiety, mood and impulse-control dysregulation be included?

    Science.gov (United States)

    Pani, Pier Paolo; Maremmani, Icro; Trogu, Emanuela; Gessa, Gian Luigi; Ruiz, Pedro; Akiskal, Hagop Souren

    2010-05-01

    Current "official" nosology (e.g. DSM IV) is largely limited to physical manifestations of addiction that can be objectively observed and are suited to the maintaining of an "atheoretical" perspective. However, addicted subjects display additional psychiatric symptoms that affect their well-being and social functioning and, in accordance with DSM IV, are typically relegated to the domain of psychiatric "comorbidity." We contend that the relationship of these psychiatric symptoms with addiction is very close, as demonstrated by the high frequency of association observed. We further assert that substance use may modify pre-existing psychic structures such as temperament and related subthreshold conditions and lead to addiction as a specific mental disorder, inclusive also of symptoms pertaining to mood/anxiety, or impulse-control dimensions. The present contribution addresses the weaknesses of the current DSM-based nosology of addiction-related mental comorbidity. We highlight the overlap of the biological substrates and the neurophysiology of addictive processes and psychiatric symptoms associated with addiction, and propose the inclusion of specific mood, anxiety, and impulse-control dimensions in the psychopathology of addictive processes. We postulate that addiction reaches beyond the mere result of drug-elicited effects on the brain and cannot be peremptorily equated only with the use of drugs despite the adverse consequences produced. We infer that mood, anxiety and impulse-control dysregulation is at the very core of both the origins and clinical manifestations of addiction and should be incorporated into the nosology of the same, emphasising how addiction is a relapsing chronic condition in which psychiatric manifestations play a crucial role. To conclude, addictionology cannot be severed from its psychopathological connotations, in view of the undeniable presence of symptoms, of their manifest contribution to the way addicted patients feel and behave, and to

  1. Posttraumatic stress and emotion dysregulation: Relationships with smoking to reduce negative affect and barriers to smoking cessation.

    Science.gov (United States)

    Short, Nicole A; Oglesby, Mary E; Raines, Amanda M; Zvolensky, Michael J; Schmidt, Norman B

    2015-08-01

    Many cigarette smokers have experienced a traumatic event, and elevated posttraumatic stress symptoms (PTSS) are associated with increased smoking levels. Previous research has found that elevated PTSS are associated with smoking to cope with negative affect, and it has been posited that perceptions of being unable to cope with the consequences of smoking cessation interfere with smoking cessation in this population. However, the mechanism of the relationship between PTSS and these smoking maintenance factors (i.e., smoking to reduce negative affect and barriers to cessation) has not been established. Emotion dysregulation is one potential mechanism as it is associated with PTSS as well as addictive behavior aimed at avoiding and reducing negative emotional states. We cross-sectionally tested the hypotheses that 1) PTSS and emotion dysregulation would be incrementally associated with smoking to reduce negative affect and barriers to cessation, and 2) that emotion dysregulation would mediate the relationships between PTSS, smoking to reduce negative affect, and barriers to cessation among a community sample of trauma-exposed individuals presenting for smoking cessation treatment (N=315). Results demonstrated that elevated PTSS were associated with increased smoking to reduce negative affect and barriers to cessation, and that emotion dysregulation mediated these relationships. These findings provide evidence of a mechanism between PTSS and psychological smoking maintenance factors, and suggest that emotion dysregulation may be a useful target for smoking cessation interventions among trauma-exposed individuals. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Automatic segmentation of vertebrae from radiographs

    DEFF Research Database (Denmark)

    Mysling, Peter; Petersen, Peter Kersten; Nielsen, Mads

    2011-01-01

    Segmentation of vertebral contours is an essential task in the design of automatic tools for vertebral fracture assessment. In this paper, we propose a novel segmentation technique which does not require operator interaction. The proposed technique solves the segmentation problem in a hierarchical...... is constrained by a conditional shape model, based on the variability of the coarse spine location estimates. The technique is evaluated on a data set of manually annotated lumbar radiographs. The results compare favorably to the previous work in automatic vertebra segmentation, in terms of both segmentation...

  3. Color image Segmentation using automatic thresholding techniques

    International Nuclear Information System (INIS)

    Harrabi, R.; Ben Braiek, E.

    2011-01-01

    In this paper, entropy and between-class variance based thresholding methods for color images segmentation are studied. The maximization of the between-class variance (MVI) and the entropy (ME) have been used as a criterion functions to determine an optimal threshold to segment images into nearly homogenous regions. Segmentation results from the two methods are validated and the segmentation sensitivity for the test data available is evaluated, and a comparative study between these methods in different color spaces is presented. The experimental results demonstrate the superiority of the MVI method for color image segmentation.

  4. MOVING WINDOW SEGMENTATION FRAMEWORK FOR POINT CLOUDS

    Directory of Open Access Journals (Sweden)

    G. Sithole

    2012-07-01

    Full Text Available As lidar point clouds become larger streamed processing becomes more attractive. This paper presents a framework for the streamed segmentation of point clouds with the intention of segmenting unstructured point clouds in real-time. The framework is composed of two main components. The first component segments points within a window shifting over the point cloud. The second component stitches the segments within the windows together. In this fashion a point cloud can be streamed through these two components in sequence, thus producing a segmentation. The algorithm has been tested on airborne lidar point cloud and some results of the performance of the framework are presented.

  5. Unsupervised Performance Evaluation of Image Segmentation

    Directory of Open Access Journals (Sweden)

    Chabrier Sebastien

    2006-01-01

    Full Text Available We present in this paper a study of unsupervised evaluation criteria that enable the quantification of the quality of an image segmentation result. These evaluation criteria compute some statistics for each region or class in a segmentation result. Such an evaluation criterion can be useful for different applications: the comparison of segmentation results, the automatic choice of the best fitted parameters of a segmentation method for a given image, or the definition of new segmentation methods by optimization. We first present the state of art of unsupervised evaluation, and then, we compare six unsupervised evaluation criteria. For this comparative study, we use a database composed of 8400 synthetic gray-level images segmented in four different ways. Vinet's measure (correct classification rate is used as an objective criterion to compare the behavior of the different criteria. Finally, we present the experimental results on the segmentation evaluation of a few gray-level natural images.

  6. Efficient graph-cut tattoo segmentation

    Science.gov (United States)

    Kim, Joonsoo; Parra, Albert; Li, He; Delp, Edward J.

    2015-03-01

    Law enforcement is interested in exploiting tattoos as an information source to identify, track and prevent gang-related crimes. Many tattoo image retrieval systems have been described. In a retrieval system tattoo segmentation is an important step for retrieval accuracy since segmentation removes background information in a tattoo image. Existing segmentation methods do not extract the tattoo very well when the background includes textures and color similar to skin tones. In this paper we describe a tattoo segmentation approach by determining skin pixels in regions near the tattoo. In these regions graph-cut segmentation using a skin color model and a visual saliency map is used to find skin pixels. After segmentation we determine which set of skin pixels are connected with each other that form a closed contour including a tattoo. The regions surrounded by the closed contours are considered tattoo regions. Our method segments tattoos well when the background includes textures and color similar to skin.

  7. Interferon Induced Focal Segmental Glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Yusuf Kayar

    2016-01-01

    Full Text Available Behçet’s disease is an inflammatory disease of unknown etiology which involves recurring oral and genital aphthous ulcers and ocular lesions as well as articular, vascular, and nervous system involvement. Focal segmental glomerulosclerosis (FSGS is usually seen in viral infections, immune deficiency syndrome, sickle cell anemia, and hyperfiltration and secondary to interferon therapy. Here, we present a case of FSGS identified with kidney biopsy in a patient who had been diagnosed with Behçet’s disease and received interferon-alpha treatment for uveitis and presented with acute renal failure and nephrotic syndrome associated with interferon.

  8. A contrario line segment detection

    CERN Document Server

    von Gioi, Rafael Grompone

    2014-01-01

    The reliable detection of low-level image structures is an old and still challenging problem in computer vision. This?book leads a detailed tour through the LSD algorithm, a line segment detector designed to be fully automatic. Based on the a contrario framework, the algorithm works efficiently without the need of any parameter tuning. The design criteria are thoroughly explained and the algorithm's good and bad results are illustrated on real and synthetic images. The issues involved, as well as the strategies used, are common to many geometrical structure detection problems and some possible

  9. Did Globalization Lead to Segmentation?

    DEFF Research Database (Denmark)

    Di Vaio, Gianfranco; Enflo, Kerstin Sofia

    Economic historians have stressed that income convergence was a key feature of the 'OECD-club' and that globalization was among the accelerating forces of this process in the long-run. This view has however been challenged, since it suffers from an ad hoc selection of countries. In the paper......, a mixture model is applied to a sample of 64 countries to endogenously analyze the cross-country growth behavior over the period 1870-2003. Results show that growth patterns were segmented in two worldwide regimes, the first one being characterized by convergence, and the other one denoted by divergence...

  10. Human cytomegalovirus infection dysregulates the canonical Wnt/β-catenin signaling pathway.

    Directory of Open Access Journals (Sweden)

    Magdalena Angelova

    Full Text Available Human Cytomegalovirus (HCMV is a ubiquitous herpesvirus that currently infects a large percentage of the world population. Although usually asymptomatic in healthy individuals, HCMV infection during pregnancy may cause spontaneous abortions, premature delivery, or permanent neurological disabilities in infants infected in utero. During infection, the virus exerts control over a multitude of host signaling pathways. Wnt/β-catenin signaling, an essential pathway involved in cell cycle control, differentiation, embryonic development, placentation and metastasis, is frequently dysregulated by viruses. How HCMV infection affects this critical pathway is not currently known. In this study, we demonstrate that HCMV dysregulates Wnt/β-catenin signaling in dermal fibroblasts and human placental extravillous trophoblasts. Infection inhibits Wnt-induced transcriptional activity of β-catenin and expression of β-catenin target genes in these cells. HCMV infection leads to β-catenin protein accumulation in a discrete juxtanuclear region. Levels of β-catenin in membrane-associated and cytosolic pools, as well as nuclear β-catenin, are reduced after infection; while transcription of the β-catenin gene is unchanged, suggesting enhanced degradation. Given the critical role of Wnt/β-catenin signaling in cellular processes, these findings represent a novel and important mechanism whereby HCMV disrupts normal cellular function.

  11. Dysregulation of heat shock protein 27 expression in oral tongue squamous cell carcinoma

    International Nuclear Information System (INIS)

    Wang, Anxun; Liu, Xiqiang; Sheng, Shihu; Ye, Hui; Peng, Tingsheng; Shi, Fei; Crowe, David L; Zhou, Xiaofeng

    2009-01-01

    Recent proteomic studies identified Hsp27 as a highly over-expressed protein in oral squamous cell carcinoma (OSCC). Clinical studies that attempted to evaluate the prognostic values of Hsp27 yielded inconsistent results, which may be due to inclusion of OSCC cases from multiple anatomic sites. In this study, to determine the utility of Hsp27 for prognosis, we focused on oral tongue SCC (OTSCC), one of the most aggressive forms of OSCC. Archival clinical samples of 15 normal oral tongue mucosa, 31 dysplastic lesions, 80 primary OTSCC, and 32 lymph node metastases were examined for Hsp27 expression by immunohistochemistry (IHC). Statistical analyses were carried out to assess the prognostic value of Hsp27 expression for patients with this disease. Dysregulation of Hsp27 expression was observed in dysplastic lesions, primary OTSCC, and lymph node metastases, and appears to be associated with disease progression. Statistical analysis revealed that the reduced Hsp27 expression in primary tumor tissue was associated with poor differentiation. Furthermore, the higher expression of Hsp27 was correlated with better overall survival. Our study confirmed that the dysregulation of Hsp27 expression is a frequent event during the progression of OTSCC. The expression of Hsp27 appears to be an independent prognostic marker for patients with this disease

  12. Early Dysregulation of Cell Adhesion and Extracellular Matrix Pathways in Breast Cancer Progression

    Science.gov (United States)

    Emery, Lyndsey A.; Tripathi, Anusri; King, Chialin; Kavanah, Maureen; Mendez, Jane; Stone, Michael D.; de las Morenas, Antonio; Sebastiani, Paola; Rosenberg, Carol L.

    2009-01-01

    Proliferative breast lesions, such as simple ductal hyperplasia (SH) and atypical ductal hyperplasia (ADH), are candidate precursors to ductal carcinoma in situ (DCIS) and invasive cancer. To better understand the relationship of breast lesions to more advanced disease, we used microdissection and DNA microarrays to profile the gene expression of patient-matched histologically normal (HN), ADH, and DCIS from 12 patients with estrogen receptor positive sporadic breast cancer. SH were profiled from a subset of cases. We found 837 differentially expressed genes between DCIS-HN and 447 between ADH-HN, with >90% of the ADH-HN genes also present among the DCIS-HN genes. Only 61 genes were identified between ADH-DCIS. Expression differences were reproduced in an independent cohort of patient-matched lesions by quantitative real-time PCR. Many breast cancer-related genes and pathways were dysregulated in ADH and maintained in DCIS. Particularly, cell adhesion and extracellular matrix interactions were overrepresented. Focal adhesion was the top pathway in each gene set. We conclude that ADH and DCIS share highly similar gene expression and are distinct from HN. In contrast, SH appear more similar to HN. These data provide genetic evidence that ADH (but not SH) are often precursors to cancer and suggest cancer-related genetic changes, particularly adhesion and extracellular matrix pathways, are dysregulated before invasion and even before malignancy is apparent. These findings could lead to novel risk stratification, prevention, and treatment approaches. PMID:19700746

  13. Commingling effect of gynoid and android fat patterns on cardiometabolic dysregulation in normal weight American adults.

    Science.gov (United States)

    Okosun, I S; Seale, J P; Lyn, R

    2015-05-18

    To determine the independent and commingling effect of android and gynoid percent fat (measured using Dual Energy X-Ray Absorptiometry) on cardiometabolic dysregulation in normal weight American adults. The 2005-2006 data (n=1802) from the United States National Health and Nutritional Examination Surveys (NHANES) were used in this study. Associations of android percent fat, gynoid percent fat and their joint occurrence with risks of cardiometabolic risk factors were estimated using prevalence odds ratios from logistic regression analyses. Android-gynoid percent fat ratio was more highly correlated with cardiometabolic dysregulation than android percent fat, gynoid percent fat or body mass index. Commingling of android and gynoid adiposities was associated with much greater odds of cardiometabolic risk factors than either android or gynoid adiposities. Commingling of android and gynoid adiposities was associated with 1.75 (95% confidence interval (CI)=1.42-2.93), 1.48 (95% CI=1.32-1.91), 1.61 (95% CI=1.50-1.89), 3.56 (95% CI=2.91-4.11) and 1.86 (95% CI=1.49-1.96) increased odds of elevated glucose, elevated blood pressure, elevated low-density lipoprotein-cholesterol, elevated triglyceride and low high-density lipoprotein-cholesterol, respectively. Normal weight subjects who present with both android and gynoid adiposities should be advised of the associated health risks. Both android and gynoid fat accumulations should be considered in developing public health strategies for reducing cardiometabolic disease risk in normal weight subjects.

  14. The detrimental effects of emotional process dysregulation on decision making in substance dependence

    Directory of Open Access Journals (Sweden)

    Anna eMurphy

    2012-11-01

    Full Text Available Substance dependence is complex and multifactorial, with many distinct pathways involved in both the development and subsequent maintenance of addictive behaviours. Various cognitive mechanisms have been implicated, including impulsivity, compulsivity and impaired decision-making. These mechanisms are modulated by emotional processes, resulting in increased likelihood of initial drug use, sustained substance dependence, and increased relapse during periods of abstinence. Emotional traits, such as sensation seeking, are risk factors for substance use, and chronic drug use can result in further emotional dysregulation via effects on reward, motivation and stress systems. We will explore theories of hyper and hypo sensitivity of the brain reward systems that may underpin motivational abnormalities and anhedonia. Disturbances in these systems contribute to the biasing of emotional processing toward cues related to drug use at the expense of natural rewards, which serves to maintain addictive behaviour, via enhanced drug craving. We will additionally focus on the sensitization of the brain stress systems that result in negative affect states that continue into protracted abstinence that is may lead to compulsive drug taking. We will explore how these emotional dysregulations impact upon decision-making controlled by goal-directed and habitual action selections systems, and, in combination with a failure of prefrontal inhibitory control, mediate maladaptive decision-making observed in substance dependent individuals such that they continue drug use in spite of negative consequences. An understanding of the emotional impacts on cognition in substance dependent individuals may guide the development of more effective therapeutic interventions.

  15. Does epigenetic dysregulation of pancreatic islets contribute to impaired insulin secretion and type 2 diabetes?

    Science.gov (United States)

    Dayeh, Tasnim; Ling, Charlotte

    2015-10-01

    β cell dysfunction is central to the development and progression of type 2 diabetes (T2D). T2D develops when β cells are not able to compensate for the increasing demand for insulin caused by insulin resistance. Epigenetic modifications play an important role in establishing and maintaining β cell identity and function in physiological conditions. On the other hand, epigenetic dysregulation can cause a loss of β cell identity, which is characterized by reduced expression of genes that are important for β cell function, ectopic expression of genes that are not supposed to be expressed in β cells, and loss of genetic imprinting. Consequently, this may lead to β cell dysfunction and impaired insulin secretion. Risk factors that can cause epigenetic dysregulation include parental obesity, an adverse intrauterine environment, hyperglycemia, lipotoxicity, aging, physical inactivity, and mitochondrial dysfunction. These risk factors can affect the epigenome at different time points throughout the lifetime of an individual and even before an individual is conceived. The plasticity of the epigenome enables it to change in response to environmental factors such as diet and exercise, and also makes the epigenome a good target for epigenetic drugs that may be used to enhance insulin secretion and potentially treat diabetes.

  16. Disorders of dysregulated signal traffic through the RAS-MAPK pathway: phenotypic spectrum and molecular mechanisms.

    Science.gov (United States)

    Tartaglia, Marco; Gelb, Bruce D

    2010-12-01

    RAS GTPases control a major signaling network implicated in several cellular functions, including cell fate determination, proliferation, survival, differentiation, migration, and senescence. Within this network, signal flow through the RAF-MEK-ERK pathway-the first identified mitogen-associated protein kinase (MAPK) cascade-mediates early and late developmental processes controlling morphology determination, organogenesis, synaptic plasticity, and growth. Signaling through the RAS-MAPK cascade is tightly controlled; and its enhanced activation represents a well-known event in oncogenesis. Unexpectedly, in the past few years, inherited dysregulation of this pathway has been recognized as the cause underlying a group of clinically related disorders sharing facial dysmorphism, cardiac defects, reduced postnatal growth, ectodermal anomalies, variable cognitive deficits, and susceptibility to certain malignancies as major features. These disorders are caused by heterozygosity for mutations in genes encoding RAS proteins, regulators of RAS function, modulators of RAS interaction with effectors, or downstream signal transducers. Here, we provide an overview of the phenotypic spectrum associated with germline mutations perturbing RAS-MAPK signaling, the unpredicted molecular mechanisms converging toward the dysregulation of this signaling cascade, and major genotype-phenotype correlations. © 2010 New York Academy of Sciences.

  17. Dopamine dysregulation hypothesis: the common basis for motivational anhedonia in major depressive disorder and schizophrenia?

    Science.gov (United States)

    Szczypiński, Jan Józef; Gola, Mateusz

    2018-03-24

    Abnormalities in reward processing are crucial symptoms of major depressive disorder (MDD) and schizophrenia (SCH). Recent neuroscientific findings regarding MDD have led to conclusions about two different symptoms related to reward processing: motivational and consummatory anhedonia, corresponding, respectively, to impaired motivation to obtain rewards ('wanting'), and diminished satisfaction from consuming them ('liking'). One can ask: which of these is common for MDD and SCH. In our review of the latest neuroscientific studies, we show that MDD and SCH do not share consummatory anhedonia, as SCH patients usually have unaltered liking. Therefore, we investigated whether motivational anhedonia is the common symptom across MDD and SCH. With regard to the similarities and differences between the neural mechanisms of MDD and SCH, here we expand the current knowledge of motivation deficits and present the common underlying mechanism of motivational anhedonia - the dopamine dysregulation hypothesis - stating that any prolonged dysregulation in tonic dopamine signaling that exceeds the given equilibrium can lead to striatal dysfunction and motivational anhedonia. The implications for further research and treatment of MDD and SCH are also discussed.

  18. The detrimental effects of emotional process dysregulation on decision-making in substance dependence

    Science.gov (United States)

    Murphy, Anna; Taylor, Eleanor; Elliott, Rebecca

    2012-01-01

    Substance dependence is complex and multifactorial, with many distinct pathways involved in both the development and subsequent maintenance of addictive behaviors. Various cognitive mechanisms have been implicated, including impulsivity, compulsivity, and impaired decision-making. These mechanisms are modulated by emotional processes, resulting in increased likelihood of initial drug use, sustained substance dependence, and increased relapse during periods of abstinence. Emotional traits, such as sensation-seeking, are risk factors for substance use, and chronic drug use can result in further emotional dysregulation via effects on reward, motivation, and stress systems. We will explore theories of hyper and hypo sensitivity of the brain reward systems that may underpin motivational abnormalities and anhedonia. Disturbances in these systems contribute to the biasing of emotional processing toward cues related to drug use at the expense of natural rewards, which serves to maintain addictive behavior, via enhanced drug craving. We will additionally focus on the sensitization of the brain stress systems that result in negative affect states that continue into protracted abstinence that is may lead to compulsive drug-taking. We will explore how these emotional dysregulations impact upon decision-making controlled by goal-directed and habitual action selections systems, and, in combination with a failure of prefrontal inhibitory control, mediate maladaptive decision-making observed in substance dependent individuals such that they continue drug use in spite of negative consequences. An understanding of the emotional impacts on cognition in substance dependent individuals may guide the development of more effective therapeutic interventions. PMID:23162443

  19. PREPAID TELECOM CUSTOMERS SEGMENTATION USING THE K-MEAN ALGORITHM

    Directory of Open Access Journals (Sweden)

    Marar Liviu Ioan

    2012-07-01

    Full Text Available The scope of relationship marketing is to retain customers and win their loyalty. This can be achieved if the companies’ products and services are developed and sold considering customers’ demands. Fulfilling customers’ demands, taken as the starting point of relationship marketing, can be obtained by acknowledging that the customers’ needs and wishes are heterogeneous. The segmentation of the customers’ base allows operators to overcome this because it illustrates the whole heterogeneous market as the sum of smaller homogeneous markets. The concept of segmentation relies on the high probability of persons grouped into segments based on common demands and behaviours to have a similar response to marketing strategies. This article focuses on the segmentation of a telecom customer base according to specific and noticeable criteria of a certain service. Although the segmentation concept is widely approached in professional literature, articles on the segmentation of a telecom customer base are very scarce, due to the strategic nature of this information. Market segmentation is carried out based on how customers spent their money on credit recharging, on making calls, on sending SMS and on Internet navigation. The method used for customer segmentation is the K-mean cluster analysis. To assess the internal cohesion of the clusters we employed the average sum of squares error indicator, and to determine the differences among the clusters we used the ANOVA and the post-hoc Tukey tests. The analyses revealed seven customer segments with different features and behaviours. The results enable the telecom company to conceive marketing strategies and planning which lead to better understanding of its customers’ needs and ultimately to a more efficient relationship with the subscribers and enhanced customer satisfaction. At the same time, the results enable the description and characterization of expenditure patterns

  20. CONSUMER SEGMENTATION OF REFILLED DRINKING WATER IN PADANG

    Directory of Open Access Journals (Sweden)

    Awisal Fasyni

    2015-05-01

    Full Text Available The purposes of this study were to analyze consumer segmentation of refilled drinking water based on their behavior and to recommend strategies for increased sales of Salju depot. The study was conducted using a survey of family and non-family consumers in Nanggalo, North Padang, West and East Padang. The respondent selection technique is using a convenience sampling, which is based on the availability of elements and easiness of obtaining these samples. The analysis used for segmentation is cluster analysis and CHAID. The results showed that there were five segments in family consumer and four segments in non-family consumer. Each family segment was different in terms of usage and consumption level, while non-family segments differ in terms of consumption duration and consumption level. Salju depot could aim market segments that provide benefits, specifically segments with high consumption levels both in family and nonfamily consumers, maintain the price and quality of the product and show the best performance in serving customers, set the open hours and optimize the messaging services.Keywords: refilled drinking water, segmentation, Padang, CHAIDABSTRAKPenelitian ini bertujuan menganalisis segmentasi konsumen air minum isi ulang berdasarkan perilakunya dan merekomendasikan strategi peningkatan penjualan bagi depot Salju. Penelitian dilakukan dengan metode survei terhadap konsumen keluarga dan konsumen nonkeluarga di Kecamatan Nanggalo, Kecamatan Padang Utara, Kecamatan Padang Barat dan Kecamatan Padang Timur Kota Padang. Teknik pemilihan responden menggunakan convenience sampling, yaitu berdasarkan ketersediaan elemen dan kemudahan mendapatkan sampel tersebut. Analisis yang digunakan untuk segmentasi adalah analisis cluster dan CHAID Hasil penelitian menunjukkan terdapat lima segmen konsumen keluarga dan empat segmen konsumen nonkeluarga. Masing-masing segmen keluarga berbeda dalam hal penggunaan dan tingkat konsumsi, sedangkan segmen

  1. Interactive segmentation for geographic atrophy in retinal fundus images.

    Science.gov (United States)

    Lee, Noah; Smith, R Theodore; Laine, Andrew F

    2008-10-01

    Fundus auto-fluorescence (FAF) imaging is a non-invasive technique for in vivo ophthalmoscopic inspection of age-related macular degeneration (AMD), the most common cause of blindness in developed countries. Geographic atrophy (GA) is an advanced form of AMD and accounts for 12-21% of severe visual loss in this disorder [3]. Automatic quantification of GA is important for determining disease progression and facilitating clinical diagnosis of AMD. The problem of automatic segmentation of pathological images still remains an unsolved problem. In this paper we leverage the watershed transform and generalized non-linear gradient operators for interactive segmentation and present an intuitive and simple approach for geographic atrophy segmentation. We compare our approach with the state of the art random walker [5] algorithm for interactive segmentation using ROC statistics. Quantitative evaluation experiments on 100 FAF images show a mean sensitivity/specificity of 98.3/97.7% for our approach and a mean sensitivity/specificity of 88.2/96.6% for the random walker algorithm.

  2. TOURISM SEGMENTATION BASED ON TOURISTS PREFERENCES: A MULTIVARIATE APPROACH

    Directory of Open Access Journals (Sweden)

    Sérgio Dominique Ferreira

    2010-11-01

    Full Text Available Over the last decades, tourism became one of the most important sectors of the international economy. Specifically in Portugal and Brazil, its contribution to Gross Domestic Product (GDP and job creation is quite relevant. In this sense, to follow a strong marketing approach on the management of tourism resources of a country comes to be paramount. Such an approach should be based on innovations which help unveil the preferences of tourists with accuracy, turning it into a competitive advantage. In this context, the main objective of the present study is to illustrate the importance and benefits associated with the use of multivariate methodologies for market segmentation. Another objective of this work is to illustrate on the importance of a post hoc segmentation. In this work, the authors applied a Cluster Analysis, with a hierarchical method followed by an  optimization method. The main results of this study allow the identification of five clusters that are distinguished by assigning special importance to certain tourism attributes at the moment of choosing a specific destination. Thus, the authors present the advantages of post hoc segmentation based on tourists’ preferences, in opposition to an a priori segmentation based on socio-demographic characteristics.

  3. Neonatal Brain Tissue Classification with Morphological Adaptation and Unified Segmentation

    Directory of Open Access Journals (Sweden)

    Richard eBeare

    2016-03-01

    Full Text Available Measuring the distribution of brain tissue types (tissue classification in neonates is necessary for studying typical and atypical brain development, such as that associated with preterm birth, and may provide biomarkers for neurodevelopmental outcomes. Compared with magnetic resonance images of adults, neonatal images present specific challenges that require the development of specialized, population-specific methods. This paper introduces MANTiS (Morphologically Adaptive Neonatal Tissue Segmentation, which extends the unified segmentation approach to tissue classification implemented in Statistical Parametric Mapping (SPM software to neonates. MANTiS utilizes a combination of unified segmentation, template adaptation via morphological segmentation tools and topological filtering, to segment the neonatal brain into eight tissue classes: cortical gray matter, white matter, deep nuclear gray matter, cerebellum, brainstem, cerebrospinal fluid (CSF, hippocampus and amygdala. We evaluated the performance of MANTiS using two independent datasets. The first dataset, provided by the NeoBrainS12 challenge, consisted of coronal T2-weighted images of preterm infants (born ≤30 weeks’ gestation acquired at 30 weeks’ corrected gestational age (n= 5, coronal T2-weighted images of preterm infants acquired at 40 weeks’ corrected gestational age (n= 5 and axial T2-weighted images of preterm infants acquired at 40 weeks’ corrected gestational age (n= 5. The second dataset, provided by the Washington University NeuroDevelopmental Research (WUNDeR group, consisted of T2-weighted images of preterm infants (born <30 weeks’ gestation acquired shortly after birth (n= 12, preterm infants acquired at term-equivalent age (n= 12, and healthy term-born infants (born ≥38 weeks’ gestation acquired within the first nine days of life (n= 12. For the NeoBrainS12 dataset, mean Dice scores comparing MANTiS with manual segmentations were all above 0.7, except for

  4. NeuroBlocks – Visual Tracking of Segmentation and Proofreading for Large Connectomics Projects

    KAUST Repository

    Al-Awami, Ali; Beyer, Johanna; Haehn, Daniel; Kasthuri, Narayanan; Lichtman, Jeff; Pfister, Hanspeter; Hadwiger, Markus

    2015-01-01

    set, providing crucial support for the management, provenance, accountability, and auditing of large-scale segmentations. We describe the design of NeuroBlocks, starting with an analysis of the domain-specific tasks, their inherent challenges, and our

  5. Novel techniques for enhancement and segmentation of acne vulgaris lesions.

    Science.gov (United States)

    Malik, A S; Humayun, J; Kamel, N; Yap, F B-B

    2014-08-01

    More than 99% acne patients suffer from acne vulgaris. While diagnosing the severity of acne vulgaris lesions, dermatologists have observed inter-rater and intra-rater variability in diagnosis results. This is because during assessment, identifying lesion types and their counting is a tedious job for dermatologists. To make the assessment job objective and easier for dermatologists, an automated system based on image processing methods is proposed in this study. There are two main objectives: (i) to develop an algorithm for the enhancement of various acne vulgaris lesions; and (ii) to develop a method for the segmentation of enhanced acne vulgaris lesions. For the first objective, an algorithm is developed based on the theory of high dynamic range (HDR) images. The proposed algorithm uses local rank transform to generate the HDR images from a single acne image followed by the log transformation. Then, segmentation is performed by clustering the pixels based on Mahalanobis distance of each pixel from spectral models of acne vulgaris lesions. Two metrics are used to evaluate the enhancement of acne vulgaris lesions, i.e., contrast improvement factor (CIF) and image contrast normalization (ICN). The proposed algorithm is compared with two other methods. The proposed enhancement algorithm shows better result than both the other methods based on CIF and ICN. In addition, sensitivity and specificity are calculated for the segmentation results. The proposed segmentation method shows higher sensitivity and specificity than other methods. This article specifically discusses the contrast enhancement and segmentation for automated diagnosis system of acne vulgaris lesions. The results are promising that can be used for further classification of acne vulgaris lesions for final grading of the lesions. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Pathogenesis of Focal Segmental Glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Beom Jin Lim

    2016-11-01

    Full Text Available Focal segmental glomerulosclerosis (FSGS is characterized by focal and segmental obliteration of glomerular capillary tufts with increased matrix. FSGS is classified as collapsing, tip, cellular, perihilar and not otherwise specified variants according to the location and character of the sclerotic lesion. Primary or idiopathic FSGS is considered to be related to podocyte injury, and the pathogenesis of podocyte injury has been actively investigated. Several circulating factors affecting podocyte permeability barrier have been proposed, but not proven to cause FSGS. FSGS may also be caused by genetic alterations. These genes are mainly those regulating slit diaphragm structure, actin cytoskeleton of podocytes, and foot process structure. The mode of inheritance and age of onset are different according to the gene involved. Recently, the role of parietal epithelial cells (PECs has been highlighted. Podocytes and PECs have common mesenchymal progenitors, therefore, PECs could be a source of podocyte repopulation after podocyte injury. Activated PECs migrate along adhesion to the glomerular tuft and may also contribute to the progression of sclerosis. Markers of activated PECs, including CD44, could be used to distinguish FSGS from minimal change disease. The pathogenesis of FSGS is very complex; however, understanding basic mechanisms of podocyte injury is important not only for basic research, but also for daily diagnostic pathology practice.

  7. Weight-Related Correlates of Psychological Dysregulation in Adolescent and Young Adult (AYA) Females with Severe Obesity

    Science.gov (United States)

    Gowey, Marissa A.; Reiter-Purtill, Jennifer; Becnel, Jennifer; Peugh, James; Mitchell, James E.; Zeller, Meg H.

    2016-01-01

    Objective Severe obesity is the fastest growing pediatric subgroup of excess weight levels. Psychological dysregulation (i.e., impairments in regulating cognitive, emotional, and/or behavioral processes) has been associated with obesity and poorer weight loss outcomes. The present study explored associations of dysregulation with weight-related variables among adolescent and young adult (AYA) females with severe obesity. Methods Fifty-four AYA females with severe obesity (MBMI=48.71 kg/m2; Mage=18.29, R=15–21 years; 59.3% White) completed self-report measures of psychological dysregulation and weight-related constructs including meal patterns, problematic eating behaviors, and body and weight dissatisfaction, as non-surgical comparison participants in a multi-site study of adolescent bariatric surgery outcomes. Pearson and bivariate correlations were conducted and stratified by age group to analyze associations between dysregulation subscales (affective, behavioral, cognitive) and weight-related variables. Results Breakfast was the most frequently skipped meal (consumed 3–4 times/week). Eating out was common (4–5 times/week) and mostly occurred at fast-food restaurants. Evening hyperphagia (61.11%) and eating in the absence of hunger (37.04%) were commonly endorsed, while unplanned eating (29.63%), a sense of loss of control over eating (22.22%), eating beyond satiety (22.22%), night eating (12.96%), and binge eating (11.11%) were less common. Almost half of the sample endorsed extreme weight dissatisfaction. Dysregulation was associated with most weight-related attitudes and behaviors of interest in young adults but select patterns emerged for adolescents. Conclusions Higher levels of psychological dysregulation are associated with greater BMI, problematic eating patterns and behaviors, and body dissatisfaction in AYA females with severe obesity. These findings have implications for developing novel intervention strategies for severe obesity in AYAs that may

  8. Technical Safety Requirements for the B695 Segment

    Energy Technology Data Exchange (ETDEWEB)

    Laycak, D

    2008-09-11

    This document contains Technical Safety Requirements (TSRs) for the Radioactive and Hazardous Waste Management (RHWM) Division's B695 Segment of the Decontamination and Waste Treatment Facility (DWTF) at Lawrence Livermore National Laboratory (LLNL). The TSRs constitute requirements regarding the safe operation of the B695 Segment. The TSRs are derived from the Documented Safety Analysis (DSA) for the B695 Segment (LLNL 2007). The analysis presented there determined that the B695 Segment is a low-chemical hazard, Hazard Category 3, nonreactor nuclear facility. The TSRs consist primarily of inventory limits as well as controls to preserve the underlying assumptions in the hazard analyses. Furthermore, appropriate commitments to safety programs are presented in the administrative controls section of the TSRs. The B695 Segment (B695 and the west portion of B696) is a waste treatment and storage facility located in the northeast quadrant of the LLNL main site. The approximate area and boundary of the B695 Segment are shown in the B695 Segment DSA. Activities typically conducted in the B695 Segment include container storage, lab-packing, repacking, overpacking, bulking, sampling, waste transfer, and waste treatment. B695 is used to store and treat radioactive, mixed, and hazardous waste, and it also contains equipment used in conjunction with waste processing operations to treat various liquid and solid wastes. The portion of the building called Building 696 Solid Waste Processing Area (SWPA), also referred to as B696S in this report, is used primarily to manage solid radioactive, mixed, and hazardous waste. Operations specific to the SWPA include sorting and segregating waste, lab-packing, sampling, and crushing empty drums that previously contained waste. Furthermore, a Waste Packaging Unit will be permitted to treat hazardous and mixed waste. RHWM generally processes LLW with no, or extremely low, concentrations of transuranics (i.e., much less than 100 n

  9. Technical Safety Requirements for the B695 Segment

    International Nuclear Information System (INIS)

    Laycak, D.

    2008-01-01

    This document contains Technical Safety Requirements (TSRs) for the Radioactive and Hazardous Waste Management (RHWM) Division's B695 Segment of the Decontamination and Waste Treatment Facility (DWTF) at Lawrence Livermore National Laboratory (LLNL). The TSRs constitute requirements regarding the safe operation of the B695 Segment. The TSRs are derived from the Documented Safety Analysis (DSA) for the B695 Segment (LLNL 2007). The analysis presented there determined that the B695 Segment is a low-chemical hazard, Hazard Category 3, nonreactor nuclear facility. The TSRs consist primarily of inventory limits as well as controls to preserve the underlying assumptions in the hazard analyses. Furthermore, appropriate commitments to safety programs are presented in the administrative controls section of the TSRs. The B695 Segment (B695 and the west portion of B696) is a waste treatment and storage facility located in the northeast quadrant of the LLNL main site. The approximate area and boundary of the B695 Segment are shown in the B695 Segment DSA. Activities typically conducted in the B695 Segment include container storage, lab-packing, repacking, overpacking, bulking, sampling, waste transfer, and waste treatment. B695 is used to store and treat radioactive, mixed, and hazardous waste, and it also contains equipment used in conjunction with waste processing operations to treat various liquid and solid wastes. The portion of the building called Building 696 Solid Waste Processing Area (SWPA), also referred to as B696S in this report, is used primarily to manage solid radioactive, mixed, and hazardous waste. Operations specific to the SWPA include sorting and segregating waste, lab-packing, sampling, and crushing empty drums that previously contained waste. Furthermore, a Waste Packaging Unit will be permitted to treat hazardous and mixed waste. RHWM generally processes LLW with no, or extremely low, concentrations of transuranics (i.e., much less than 100 n

  10. Brain Tumor Image Segmentation in MRI Image

    Science.gov (United States)

    Peni Agustin Tjahyaningtijas, Hapsari

    2018-04-01

    Brain tumor segmentation plays an important role in medical image processing. Treatment of patients with brain tumors is highly dependent on early detection of these tumors. Early detection of brain tumors will improve the patient’s life chances. Diagnosis of brain tumors by experts usually use a manual segmentation that is difficult and time consuming because of the necessary automatic segmentation. Nowadays automatic segmentation is very populer and can be a solution to the problem of tumor brain segmentation with better performance. The purpose of this paper is to provide a review of MRI-based brain tumor segmentation methods. There are number of existing review papers, focusing on traditional methods for MRI-based brain tumor image segmentation. this paper, we focus on the recent trend of automatic segmentation in this field. First, an introduction to brain tumors and methods for brain tumor segmentation is given. Then, the state-of-the-art algorithms with a focus on recent trend of full automatic segmentaion are discussed. Finally, an assessment of the current state is presented and future developments to standardize MRI-based brain tumor segmentation methods into daily clinical routine are addressed.

  11. A new framework for interactive images segmentation

    International Nuclear Information System (INIS)

    Ashraf, M.; Sarim, M.; Shaikh, A.B.

    2017-01-01

    Image segmentation has become a widely studied research problem in image processing. There exist different graph based solutions for interactive image segmentation but the domain of image segmentation still needs persistent improvements. The segmentation quality of existing techniques generally depends on the manual input provided in beginning, therefore, these algorithms may not produce quality segmentation with initial seed labels provided by a novice user. In this work we investigated the use of cellular automata in image segmentation and proposed a new algorithm that follows a cellular automaton in label propagation. It incorporates both the pixel's local and global information in the segmentation process. We introduced the novel global constraints in automata evolution rules; hence proposed scheme of automata evolution is more effective than the automata based earlier evolution schemes. Global constraints are also effective in deceasing the sensitivity towards small changes made in manual input; therefore proposed approach is less dependent on label seed marks. It can produce the quality segmentation with modest user efforts. Segmentation results indicate that the proposed algorithm performs better than the earlier segmentation techniques. (author)

  12. Fully convolutional neural networks improve abdominal organ segmentation

    Science.gov (United States)

    Bobo, Meg F.; Bao, Shunxing; Huo, Yuankai; Yao, Yuang; Virostko, Jack; Plassard, Andrew J.; Lyu, Ilwoo; Assad, Albert; Abramson, Richard G.; Hilmes, Melissa A.; Landman, Bennett A.

    2018-03-01

    Abdominal image segmentation is a challenging, yet important clinical problem. Variations in body size, position, and relative organ positions greatly complicate the segmentation process. Historically, multi-atlas methods have achieved leading results across imaging modalities and anatomical targets. However, deep learning is rapidly overtaking classical approaches for image segmentation. Recently, Zhou et al. showed that fully convolutional networks produce excellent results in abdominal organ segmentation of computed tomography (CT) scans. Yet, deep learning approaches have not been applied to whole abdomen magnetic resonance imaging (MRI) segmentation. Herein, we evaluate the applicability of an existing fully convolutional neural network (FCNN) designed for CT imaging to segment abdominal organs on T2 weighted (T2w) MRI's with two examples. In the primary example, we compare a classical multi-atlas approach with FCNN on forty-five T2w MRI's acquired from splenomegaly patients with five organs labeled (liver, spleen, left kidney, right kidney, and stomach). Thirty-six images were used for training while nine were used for testing. The FCNN resulted in a Dice similarity coefficient (DSC) of 0.930 in spleens, 0.730 in left kidneys, 0.780 in right kidneys, 0.913 in livers, and 0.556 in stomachs. The performance measures for livers, spleens, right kidneys, and stomachs were significantly better than multi-atlas (p < 0.05, Wilcoxon rank-sum test). In a secondary example, we compare the multi-atlas approach with FCNN on 138 distinct T2w MRI's with manually labeled pancreases (one label). On the pancreas dataset, the FCNN resulted in a median DSC of 0.691 in pancreases versus 0.287 for multi-atlas. The results are highly promising given relatively limited training data and without specific training of the FCNN model and illustrate the potential of deep learning approaches to transcend imaging modalities. 1

  13. Segmentation of dance movement: Effects of expertise, visual familiarity, motor experience and music

    Directory of Open Access Journals (Sweden)

    Bettina E. Bläsing

    2015-01-01

    Full Text Available According to event segmentation theory, action perception depends on sensory cues and prior knowledge, and the segmentation of observed actions is crucial for understanding and memorizing these actions. While most activities in everyday life are characterized by external goals and interaction with objects or persons, this does not necessarily apply to dance-like actions. We investigated to what extent visual familiarity of the observed movement and accompanying music influence the segmentation of a dance phrase in dancers of different skill level and non-dancers. In Experiment 1, dancers and non-dancers repeatedly watched a video clip showing a dancer performing a choreographed dance phrase and indicated segment boundaries by key press. Dancers generally defined less segment boundaries than non-dancers, specifically in the first trials in which visual familiarity with the phrase was low. Music increased the number of segment boundaries in the non-dancers and decreased it in the dancers. The results suggest that dance expertise reduces the number of perceived segment boundaries in an observed dance phrase, and that the ways visual familiarity and music affect movement segmentation are modulated by dance expertise. In a second experiment, motor experience was added as factor, based on empirical evidence suggesting that action perception is modified by visual and motor expertise in different ways. In Experiment 2, the same task as in Experiment 1 was performed by dance amateurs, and was repeated by the same participants after they had learned to dance the presented dance phrase. Less segment boundaries were defined in the middle trials after participants had learned to dance the phrase, and music reduced the number of segment boundaries before learning. The results suggest that specific motor experience of the observed movement influences its perception and anticipation and makes segmentation broader, but not to the same degree as dance expertise

  14. Arizona TeleMedicine Network: Segment Specifications--Tuba City via Mt. Elden, Phoenix; Keams Canyon, Second Mesa, Low Mountain; Phoenix, San Carlos, Bylas; Keams Canyon via Ganado Mesa, Ft. Defiance; Tuba City via Black Mesa, Ft. Defiance; and Budgetary Cost Information--Pinal Peak via San Xavier, Tucson.

    Science.gov (United States)

    Atlantic Research Corp., Alexandria, VA.

    The communication links of five different segments of the Arizona TeleMedicine Network (a telecommunication system designed to provide health services for American Indians in rurally isolated areas) and budgetary cost information for Pinal Peak via San Xavier and Tucson are described in this document. The five communication links are identified…

  15. A systematic review of definitions and classification systems of adjacent segment pathology.

    Science.gov (United States)

    Kraemer, Paul; Fehlings, Michael G; Hashimoto, Robin; Lee, Michael J; Anderson, Paul A; Chapman, Jens R; Raich, Annie; Norvell, Daniel C

    2012-10-15

    Systematic review. To undertake a systematic review to determine how "adjacent segment degeneration," "adjacent segment disease," or clinical pathological processes that serve as surrogates for adjacent segment pathology are classified and defined in the peer-reviewed literature. Adjacent segment degeneration and adjacent segment disease are terms referring to degenerative changes known to occur after reconstructive spine surgery, most commonly at an immediately adjacent functional spinal unit. These can include disc degeneration, instability, spinal stenosis, facet degeneration, and deformity. The true incidence and clinical impact of degenerative changes at the adjacent segment is unclear because there is lack of a universally accepted classification system that rigorously addresses clinical and radiological issues. A systematic review of the English language literature was undertaken and articles were classified using the Grades of Recommendation Assessment, Development, and Evaluation criteria. RESULTS.: Seven classification systems of spinal degeneration, including degeneration at the adjacent segment, were identified. None have been evaluated for reliability or validity specific to patients with degeneration at the adjacent segment. The ways in which terms related to adjacent segment "degeneration" or "disease" are defined in the peer-reviewed literature are highly variable. On the basis of the systematic review presented in this article, no formal classification system for either cervical or thoracolumbar adjacent segment disorders currently exists. No recommendations regarding the use of current classification of degeneration at any segments can be made based on the available literature. A new comprehensive definition for adjacent segment pathology (ASP, the now preferred terminology) has been proposed in this Focus Issue, which reflects the diverse pathology observed at functional spinal units adjacent to previous spinal reconstruction and balances

  16. Hierarchical image segmentation for learning object priors

    Energy Technology Data Exchange (ETDEWEB)

    Prasad, Lakshman [Los Alamos National Laboratory; Yang, Xingwei [TEMPLE UNIV.; Latecki, Longin J [TEMPLE UNIV.; Li, Nan [TEMPLE UNIV.

    2010-11-10

    The proposed segmentation approach naturally combines experience based and image based information. The experience based information is obtained by training a classifier for each object class. For a given test image, the result of each classifier is represented as a probability map. The final segmentation is obtained with a hierarchial image segmentation algorithm that considers both the probability maps and the image features such as color and edge strength. We also utilize image region hierarchy to obtain not only local but also semi-global features as input to the classifiers. Moreover, to get robust probability maps, we take into account the region context information by averaging the probability maps over different levels of the hierarchical segmentation algorithm. The obtained segmentation results are superior to the state-of-the-art supervised image segmentation algorithms.

  17. Image Segmentation Using Minimum Spanning Tree

    Science.gov (United States)

    Dewi, M. P.; Armiati, A.; Alvini, S.

    2018-04-01

    This research aim to segmented the digital image. The process of segmentation is to separate the object from the background. So the main object can be processed for the other purposes. Along with the development of technology in digital image processing application, the segmentation process becomes increasingly necessary. The segmented image which is the result of the segmentation process should accurate due to the next process need the interpretation of the information on the image. This article discussed the application of minimum spanning tree on graph in segmentation process of digital image. This method is able to separate an object from the background and the image will change to be the binary images. In this case, the object that being the focus is set in white, while the background is black or otherwise.

  18. Toxic Anterior Segment Syndrome (TASS

    Directory of Open Access Journals (Sweden)

    Özlem Öner

    2011-12-01

    Full Text Available Toxic anterior segment syndrome (TASS is a sterile intraocular inflammation caused by noninfectious substances, resulting in extensive toxic damage to the intraocular tissues. Possible etiologic factors of TASS include surgical trauma, bacterial endotoxin, intraocular solutions with inappropriate pH and osmolality, preservatives, denatured ophthalmic viscosurgical devices (OVD, inadequate sterilization, cleaning and rinsing of surgical devices, intraocular lenses, polishing and sterilizing compounds which are related to intraocular lenses. The characteristic signs and symptoms such as blurred vision, corneal edema, hypopyon and nonreactive pupil usually occur 24 hours after the cataract surgery. The differential diagnosis of TASS from infectious endophthalmitis is important. The main treatment for TASS formation is prevention. TASS is a cataract surgery complication that is more commonly seen nowadays. In this article, the possible underlying causes as well as treatment and prevention methods of TASS are summarized. (Turk J Oph thal mol 2011; 41: 407-13

  19. Communication with market segments - travel agencies' perspective

    OpenAIRE

    Lorena Bašan; Jasmina Dlačić; Željko Trezner

    2013-01-01

    Purpose – The purpose of this paper is to research the travel agencies’ communication with market segments. Communication with market segments takes into account marketing communication means as well as the implementation of different business orientations. Design – Special emphasis is placed on the use of different marketing communication means and their efficiency. Research also explores business orientation adaptation when approaching different market segments. Methodology – In explo...

  20. Distance measures for image segmentation evaluation

    OpenAIRE

    Monteiro, Fernando C.; Campilho, Aurélio

    2012-01-01

    In this paper we present a study of evaluation measures that enable the quantification of the quality of an image segmentation result. Despite significant advances in image segmentation techniques, evaluation of these techniques thus far has been largely subjective. Typically, the effectiveness of a new algorithm is demonstrated only by the presentation of a few segmented images and is otherwise left to subjective evaluation by the reader. Such an evaluation criterion can be useful for differ...