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Sample records for spm analysis identified

  1. Unified ICA-SPM analysis of fMRI experiments

    DEFF Research Database (Denmark)

    Bjerre, Troels; Henriksen, Jonas; Nielsen, Carsten Haagen

    2009-01-01

    We present a toolbox for exploratory analysis of functional magnetic resonance imaging (fMRI) data using independent component analysis (ICA) within the widely used SPM analysis pipeline. The toolbox enables dimensional reduction using principal component analysis, ICA using several different ICA...

  2. EEG and MEG Data Analysis in SPM8

    Directory of Open Access Journals (Sweden)

    Vladimir Litvak

    2011-01-01

    Full Text Available SPM is a free and open source software written in MATLAB (The MathWorks, Inc.. In addition to standard M/EEG preprocessing, we presently offer three main analysis tools: (i statistical analysis of scalp-maps, time-frequency images, and volumetric 3D source reconstruction images based on the general linear model, with correction for multiple comparisons using random field theory; (ii Bayesian M/EEG source reconstruction, including support for group studies, simultaneous EEG and MEG, and fMRI priors; (iii dynamic causal modelling (DCM, an approach combining neural modelling with data analysis for which there are several variants dealing with evoked responses, steady state responses (power spectra and cross-spectra, induced responses, and phase coupling. SPM8 is integrated with the FieldTrip toolbox , making it possible for users to combine a variety of standard analysis methods with new schemes implemented in SPM and build custom analysis tools using powerful graphical user interface (GUI and batching tools.

  3. Analysis of brain SPECT with the statistical parametric mapping package SPM99

    International Nuclear Information System (INIS)

    Barnden, L.R.; Rowe, C.C.

    2000-01-01

    Full text: The Statistical Parametric Mapping (SPM) package of the Welcome Department of Cognitive Neurology permits detection in the brain of different regional uptake in an individual subject or a population of subjects compared to a normal population. SPM does not require a-priori specification of regions of interest. Recently SPM has been upgraded from SPM96 to SPM99. Our aim was to vary brain SPECT processing options in the application of SPM to optimise the final statistical map in three clinical trials. The sensitivity of SPM depends on the fidelity of the preliminary spatial normalisation of each scan to the standard anatomical space defined by a template scan provided with SPM. We generated our own SPECT template and compared spatial normalisation to it and to SPM's internal PET template. We also investigated the effects of scatter subtraction, stripping of scalp activity, reconstruction algorithm, non-linear deformation and derivation of spatial normalisation parameters using co-registered MR. Use of our SPECT template yielded better results than with SPM's PET template. Accuracy of SPECT to MR co-registration was 2.5mm with SPM96 and 1.2mm with SPM99. Stripping of scalp activity improved results with SPM96 but was unnecessary with SPM99. Scatter subtraction increased the sensitivity of SPM. Non-linear deformation additional to linear (affine) transformation only marginally improved the final result. Use of the SPECT template yielded more significant results than those obtained when co registered MR was used to derive the transformation parameters. SPM99 is more robust than SPM96 and optimum SPECT analysis requires a SPECT template. Copyright (2000) The Australian and New Zealand Society of Nuclear Medicine Inc

  4. Brain SPECT in mesial temporal lobe epilepsy: comparison between visual analysis and SPM (Statistical Parametric Mapping)

    Energy Technology Data Exchange (ETDEWEB)

    Amorim, Barbara Juarez; Ramos, Celso Dario; Santos, Allan Oliveira dos; Lima, Mariana da Cunha Lopes de; Camargo, Edwaldo Eduardo; Etchebehere, Elba Cristina Sa de Camargo, E-mail: juarezbarbara@hotmail.co [State University of Campinas (UNICAMP), SP (Brazil). School of Medical Sciences. Dept. of Radiology; Min, Li Li; Cendes, Fernando [State University of Campinas (UNICAMP), SP (Brazil). School of Medical Sciences. Dept. of Neurology

    2010-04-15

    Objective: to compare the accuracy of SPM and visual analysis of brain SPECT in patients with mesial temporal lobe epilepsy (MTLE). Method: interictal and ictal SPECTs of 22 patients with MTLE were performed. Visual analysis were performed in interictal (VISUAL(inter)) and ictal (VISUAL(ictal/inter)) studies. SPM analysis consisted of comparing interictal (SPM(inter)) and ictal SPECTs (SPM(ictal)) of each patient to control group and by comparing perfusion of temporal lobes in ictal and interictal studies among themselves (SPM(ictal/inter)). Results: for detection of the epileptogenic focus, the sensitivities were as follows: VISUAL(inter)=68%; VISUAL(ictal/inter)=100%; SPM(inter)=45%; SPM(ictal)=64% and SPM(ictal/inter)=77%. SPM was able to detect more areas of hyperperfusion and hypoperfusion. Conclusion: SPM did not improve the sensitivity to detect epileptogenic focus. However, SPM detected different regions of hypoperfusion and hyperperfusion and is therefore a helpful tool for better understand pathophysiology of seizures in MTLE. (author)

  5. Brain SPECT in mesial temporal lobe epilepsy: comparison between visual analysis and SPM (Statistical Parametric Mapping)

    International Nuclear Information System (INIS)

    Amorim, Barbara Juarez; Ramos, Celso Dario; Santos, Allan Oliveira dos; Lima, Mariana da Cunha Lopes de; Camargo, Edwaldo Eduardo; Etchebehere, Elba Cristina Sa de Camargo; Min, Li Li; Cendes, Fernando

    2010-01-01

    Objective: to compare the accuracy of SPM and visual analysis of brain SPECT in patients with mesial temporal lobe epilepsy (MTLE). Method: interictal and ictal SPECTs of 22 patients with MTLE were performed. Visual analysis were performed in interictal (VISUAL(inter)) and ictal (VISUAL(ictal/inter)) studies. SPM analysis consisted of comparing interictal (SPM(inter)) and ictal SPECTs (SPM(ictal)) of each patient to control group and by comparing perfusion of temporal lobes in ictal and interictal studies among themselves (SPM(ictal/inter)). Results: for detection of the epileptogenic focus, the sensitivities were as follows: VISUAL(inter)=68%; VISUAL(ictal/inter)=100%; SPM(inter)=45%; SPM(ictal)=64% and SPM(ictal/inter)=77%. SPM was able to detect more areas of hyperperfusion and hypoperfusion. Conclusion: SPM did not improve the sensitivity to detect epileptogenic focus. However, SPM detected different regions of hypoperfusion and hyperperfusion and is therefore a helpful tool for better understand pathophysiology of seizures in MTLE. (author)

  6. Sparse SPM: Group Sparse-dictionary learning in SPM framework for resting-state functional connectivity MRI analysis.

    Science.gov (United States)

    Lee, Young-Beom; Lee, Jeonghyeon; Tak, Sungho; Lee, Kangjoo; Na, Duk L; Seo, Sang Won; Jeong, Yong; Ye, Jong Chul

    2016-01-15

    Recent studies of functional connectivity MR imaging have revealed that the default-mode network activity is disrupted in diseases such as Alzheimer's disease (AD). However, there is not yet a consensus on the preferred method for resting-state analysis. Because the brain is reported to have complex interconnected networks according to graph theoretical analysis, the independency assumption, as in the popular independent component analysis (ICA) approach, often does not hold. Here, rather than using the independency assumption, we present a new statistical parameter mapping (SPM)-type analysis method based on a sparse graph model where temporal dynamics at each voxel position are described as a sparse combination of global brain dynamics. In particular, a new concept of a spatially adaptive design matrix has been proposed to represent local connectivity that shares the same temporal dynamics. If we further assume that local network structures within a group are similar, the estimation problem of global and local dynamics can be solved using sparse dictionary learning for the concatenated temporal data across subjects. Moreover, under the homoscedasticity variance assumption across subjects and groups that is often used in SPM analysis, the aforementioned individual and group analyses using sparse dictionary learning can be accurately modeled by a mixed-effect model, which also facilitates a standard SPM-type group-level inference using summary statistics. Using an extensive resting fMRI data set obtained from normal, mild cognitive impairment (MCI), and Alzheimer's disease patient groups, we demonstrated that the changes in the default mode network extracted by the proposed method are more closely correlated with the progression of Alzheimer's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. SPM analysis and cognitive dysfunctions in patients with transient global amnesia

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Young Jin; Kang, Do Young; Yun, Go Un; Park, Kyung Won; Kim, Jae Woo [School of Medicine, Donga University, Busan (Korea, Republic of)

    2004-07-01

    Transient global amnesia (TGA) is known as a disease of benign nature characterized with clinically transient global antegrade amnesia and a variable degree of global retrograde memory impairment, but it usually resolved within 24 hours. The aims of this study are to assess the alterations in regional cerebral blood flow (rCBF) by Tc-99m HMPAO SPECT imaging with statistical parametric mapping (SPM) analysis and to verify the cognitive deficits by neuropsychological test in TGA patients. Twelve patients with TGA and age-matched normal control subjects participated in this study. Tc-99m HMPAO SPECT was performed within 1 to 19 days (mean duration: 7.3:{+-}5.2 days) after the events to measure the rCBF. SPECT images were analyzed using SPM (SPM99) with Matlab 5.3. Seoul Neuropsychological Screening Battery test was also done within 2 to 8 days (mean duration 3.8{+-}2.2 days) for cognitive functions in 8 of 12 patients with TGA. The SPM analysis of SPECT images showed significantly decreased rCBF in the left inferior frontal gyrus (Brodmann area 9), the left supramarginal gyrus (Brodmann area 40), the left postcentral gyrus (Brodmann area 40) and the left precentral gyrus (Brodmann area 4) in patients with TGA (uncorrected p<0.01). Neuropsychological test findings represented that several cognitive functions. such as, verbal memory, visual memory, phonemic fluency and confrontational naming, were impaired in patients with TGA compared with normal control. Additionally, on SPM analysis, we found lesions of hyperperfusion in contralateral cerebral hemisphere. Our study shows perfusion deficits in the left cerebral hemisphere in patients with TGA and several cognitive dysfunctions. And we found after clinical symptoms were completely resolved, the lesions of hypoperfusion were still remained. We found that functional quantitative neuroimaging study and neuropsychological test are useful to understand underlying pathomachanism of TGA.

  8. SPM analysis and cognitive dysfunctions in patients with transient global amnesia

    International Nuclear Information System (INIS)

    Jeong, Young Jin; Kang, Do Young; Yun, Go Un; Park, Kyung Won; Kim, Jae Woo

    2004-01-01

    Transient global amnesia (TGA) is known as a disease of benign nature characterized with clinically transient global antegrade amnesia and a variable degree of global retrograde memory impairment, but it usually resolved within 24 hours. The aims of this study are to assess the alterations in regional cerebral blood flow (rCBF) by Tc-99m HMPAO SPECT imaging with statistical parametric mapping (SPM) analysis and to verify the cognitive deficits by neuropsychological test in TGA patients. Twelve patients with TGA and age-matched normal control subjects participated in this study. Tc-99m HMPAO SPECT was performed within 1 to 19 days (mean duration: 7.3:±5.2 days) after the events to measure the rCBF. SPECT images were analyzed using SPM (SPM99) with Matlab 5.3. Seoul Neuropsychological Screening Battery test was also done within 2 to 8 days (mean duration 3.8±2.2 days) for cognitive functions in 8 of 12 patients with TGA. The SPM analysis of SPECT images showed significantly decreased rCBF in the left inferior frontal gyrus (Brodmann area 9), the left supramarginal gyrus (Brodmann area 40), the left postcentral gyrus (Brodmann area 40) and the left precentral gyrus (Brodmann area 4) in patients with TGA (uncorrected p<0.01). Neuropsychological test findings represented that several cognitive functions. such as, verbal memory, visual memory, phonemic fluency and confrontational naming, were impaired in patients with TGA compared with normal control. Additionally, on SPM analysis, we found lesions of hyperperfusion in contralateral cerebral hemisphere. Our study shows perfusion deficits in the left cerebral hemisphere in patients with TGA and several cognitive dysfunctions. And we found after clinical symptoms were completely resolved, the lesions of hypoperfusion were still remained. We found that functional quantitative neuroimaging study and neuropsychological test are useful to understand underlying pathomachanism of TGA

  9. Visual and SPM analysis of regional cerebral glucose metabolism in adult patients with neurofibromatosis

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Joon Kee; An, Young Sil; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam [Ajou University, School of Medicine, Suwon (Korea, Republic of)

    2005-07-01

    We evaluated the regional cerebral glucose metabolism in adult patients with neurofibromatosis (NF) using visual and SPM analysis, and compared with MRI findings. A total of 11 adult patients with NF type I were prospectively included in the study. All patients underwent F-18 FDG PET and brain MRI within 2 month of each other. All hypometabolic areas on PET were determined visually by 2 nuclear medicine physician and compared with MRI findings. SPM analysis was done using 42 normal controls with p = 0.005. Seven of 11 PET images showed 10 hypometabolic areas and 4 of 11 MRIs showed 6 areas of signal change brain parenchyma. Hypometabolic areas were bilateral thalamus (n=5), left temporal cortex (n=4) and dentate nucleus (n=1). In only 2 lesions (thalamus and dentate nucleus), hypometabolic foci were consistently related to signal change on MRI. SPM analysis revealed significantly decreased area in bilateral thalamus and left temporal cortex. F-18 FDG PET revealed significant hypometabolism in bilateral thalamus and left temporal cortex in adult patients with NF, and it might be helpful in understanding developmental abnormality of NF.

  10. Quantitative analysis of diffusion tensor imaging (DTI) using statistical parametric mapping (SPM) for brain disorders

    Science.gov (United States)

    Lee, Jae-Seung; Im, In-Chul; Kang, Su-Man; Goo, Eun-Hoe; Kwak, Byung-Joon

    2013-07-01

    This study aimed to quantitatively analyze data from diffusion tensor imaging (DTI) using statistical parametric mapping (SPM) in patients with brain disorders and to assess its potential utility for analyzing brain function. DTI was obtained by performing 3.0-T magnetic resonance imaging for patients with Alzheimer's disease (AD) and vascular dementia (VD), and the data were analyzed using Matlab-based SPM software. The two-sample t-test was used for error analysis of the location of the activated pixels. We compared regions of white matter where the fractional anisotropy (FA) values were low and the apparent diffusion coefficients (ADCs) were increased. In the AD group, the FA values were low in the right superior temporal gyrus, right inferior temporal gyrus, right sub-lobar insula, and right occipital lingual gyrus whereas the ADCs were significantly increased in the right inferior frontal gyrus and right middle frontal gyrus. In the VD group, the FA values were low in the right superior temporal gyrus, right inferior temporal gyrus, right limbic cingulate gyrus, and right sub-lobar caudate tail whereas the ADCs were significantly increased in the left lateral globus pallidus and left medial globus pallidus. In conclusion by using DTI and SPM analysis, we were able to not only determine the structural state of the regions affected by brain disorders but also quantitatively analyze and assess brain function.

  11. Correlation of regional cerebral blood flow and positive/negative symptoms in schizophrenic patients: covariate SPM analysis

    International Nuclear Information System (INIS)

    Lim, Ki Chun; Kim, J. S.; Kim, C. Y.; Lee, H. K.; Moon, D. H.

    2002-01-01

    We investigated the relations between rCBF and psychopathology in schizophrenic patients using a SPM99. Thirty-two patients(M/F:22/10, 25±5,6yr) with active symptoms of schizophrenia and 15 age matched normal controls underwent Tc-99m ECD brain perfusion SPECT. Psychopathology of all patients were also assessed according to PANSS (positive and negative syndrome scale in schizophrenia). By covariate SPM analysis, specific areas where rCBF correlated with sum scores of positive/negative synptoms were identified. Regional CBF of schizophrenics was different in several cortical regions from normal controls. Sum scores of positive symptoms were positively correlated with rCBF of both rectal and inferior frontal gyri and right transverse temporal gyrus, and negatively correlated with rCBF of left lingual and right middle temporal gyri (p<0.01). Sum scores of negative symptoms were positively correlated with rCBF of both middle temporal gyri and negatively correlated with rCBF of right superior parietal lobule and medial frontal gyrus (p<0.01). Positive and negative symptoms of schizophrenia were correlated with rCBF change in different regions of cerebral association cortex

  12. Correlation of regional cerebral blood flow and positive/negative symptoms in schizophrenic patients: covariate SPM analysis

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Ki Chun; Kim, J. S.; Kim, C. Y.; Lee, H. K.; Moon, D. H. [Ulsan University, Seoul (Korea, Republic of)

    2002-07-01

    We investigated the relations between rCBF and psychopathology in schizophrenic patients using a SPM99. Thirty-two patients(M/F:22/10, 25{+-}5,6yr) with active symptoms of schizophrenia and 15 age matched normal controls underwent Tc-99m ECD brain perfusion SPECT. Psychopathology of all patients were also assessed according to PANSS (positive and negative syndrome scale in schizophrenia). By covariate SPM analysis, specific areas where rCBF correlated with sum scores of positive/negative synptoms were identified. Regional CBF of schizophrenics was different in several cortical regions from normal controls. Sum scores of positive symptoms were positively correlated with rCBF of both rectal and inferior frontal gyri and right transverse temporal gyrus, and negatively correlated with rCBF of left lingual and right middle temporal gyri (p<0.01). Sum scores of negative symptoms were positively correlated with rCBF of both middle temporal gyri and negatively correlated with rCBF of right superior parietal lobule and medial frontal gyrus (p<0.01). Positive and negative symptoms of schizophrenia were correlated with rCBF change in different regions of cerebral association cortex.

  13. Heavy metal analysis of suspended particulate matter (SPM) and other samples from some workplaces in Kenya

    International Nuclear Information System (INIS)

    Kinyua, A.M.; Gatebe, C.K.; Mangala, M.J.

    1998-01-01

    Air pollution studies in Nairobi are indicating a rising trend in the particulate matter loading. The trend is mainly attributed to increased volume of motor vehicles, the physical change of the environment, agricultural and industrial activities. In this study, total suspended particulate matter sampling at the Nairobi industrial area and inside one workplace are reported. Included also are the results of analysis of water samples and effluents collected from a sugar factory, a tannery, and mercury (Hg) analysis in some beauty creams sold in Nairobi. The samples were analysed for heavy metal content using Energy Dispersive X-ray Fluorescence (EDXRF) while the suspended particulate matter (SPM) concentrations were determined by gravimetric technique. Total reflection x-ray fluorescence (TRXF), atomic absorption spectrophotometry and PIXE analytical techniques plus the use of Standard and Certified Reference Materials (SRM's and CRM's) were used for quality control, analysis and evaluation of the accrued data. Air sampling in the industrial area was done twice (Wednesday and Saturday) every week for a period of two months (November and December, 1996) and twice monthly for a period of six months (January-June 1997). Each sample covering approximately 24 hours, was collected using the 'Gent' Stacked Filter Unit (SFU), for day and night times. The SPM were found to vary from 16 to 83 mgm -3 during the sampling period. The analysis of dust collected inside a workplace showed that there was poor filtration of the air pumped into the building and that there was a need for improvement of the air conditioning unit plus reduction of emissions from a neighbouring tyre factory. Beauty creams analysed showed that there is some mercury present in significant amounts (0.14 - 3.0%). The results of these mercury levels are presented for various brands of cosmetics sold in some market outlets in Nairobi. The health implications on the presence of mercury in some of these beauty

  14. SPM analysis of cerebral blood flow changes related to age in patients with schizophrenia

    Energy Technology Data Exchange (ETDEWEB)

    Song, Ho Chun; Kim, Sung Wan; Lee, Byeong II; Min, Jung Joon; Bom, Hee Seung [Chonnam National University Medical School, Gwangju (Korea, Republic of)

    2007-07-01

    The goal of this study was to explore neural activities of schizophrenic patients related to current age including the age of onset and also we examined the correlation patterns between age and neural correlates. 21 patients with schizophrenia (female/male; 10/11, mean age; 36.1 11.2) participated in this study and all patients were evaluated by criteria of DSM-IV as a schizophrenia patient. Exclusion criteria included inability to give informed consent and a history of significant neurological illness. 99mTc-ECD brain perfusion SPECT images were obtained from 21 schizophrenic patients. Using SPM (statistical parametric mapping), all images were normalized to a SPECT template (MNI template) and then smoothed. We performed an ANCOVA analysis with current age (covariate variable) and the age of onset (nuisance variable). The correlation was analyzed into positive and negative patterns. Findings are reported as a Z scores with a significance threshold of p < 0.005 (uncorrected) and a minimum cluster size of 10. Significant difference was found between current age and premorbid age (p < 0.05). Cerebral regions that were positively correlated with current age were observed in the middle frontal gyrus and the superior frontal gyrus bilaterally, the left precentral gyrus (Brodmann's area; BA 9) and the right inferior frontal gyrus (BA 46). Also, in relation to negative correlations, there were many regions in the right posterior cingulate gyrus (BA 30) and the left cuneus (BA 30), middle temporal gyrus (BA 21) and superior temporal gyrus (BA 13, 39). Additionally, the occipital regions were found in the right cuneus (BA 18) including the right middle occipital gyrus (BA 18) and right lingual gyrus (BA 19). Age effect in schizophrenic patients was observed in the dorsolateral prefrontal cortex with positive correlation. We suggest that the dorsolateral prefrontal cortex activity which is important for cognitive task performance is related to an increase of patients

  15. SPM analysis of cerebral blood flow changes related to age in patients with schizophrenia

    International Nuclear Information System (INIS)

    Song, Ho Chun; Kim, Sung Wan; Lee, Byeong II; Min, Jung Joon; Bom, Hee Seung

    2007-01-01

    The goal of this study was to explore neural activities of schizophrenic patients related to current age including the age of onset and also we examined the correlation patterns between age and neural correlates. 21 patients with schizophrenia (female/male; 10/11, mean age; 36.1 11.2) participated in this study and all patients were evaluated by criteria of DSM-IV as a schizophrenia patient. Exclusion criteria included inability to give informed consent and a history of significant neurological illness. 99mTc-ECD brain perfusion SPECT images were obtained from 21 schizophrenic patients. Using SPM (statistical parametric mapping), all images were normalized to a SPECT template (MNI template) and then smoothed. We performed an ANCOVA analysis with current age (covariate variable) and the age of onset (nuisance variable). The correlation was analyzed into positive and negative patterns. Findings are reported as a Z scores with a significance threshold of p < 0.005 (uncorrected) and a minimum cluster size of 10. Significant difference was found between current age and premorbid age (p < 0.05). Cerebral regions that were positively correlated with current age were observed in the middle frontal gyrus and the superior frontal gyrus bilaterally, the left precentral gyrus (Brodmann's area; BA 9) and the right inferior frontal gyrus (BA 46). Also, in relation to negative correlations, there were many regions in the right posterior cingulate gyrus (BA 30) and the left cuneus (BA 30), middle temporal gyrus (BA 21) and superior temporal gyrus (BA 13, 39). Additionally, the occipital regions were found in the right cuneus (BA 18) including the right middle occipital gyrus (BA 18) and right lingual gyrus (BA 19). Age effect in schizophrenic patients was observed in the dorsolateral prefrontal cortex with positive correlation. We suggest that the dorsolateral prefrontal cortex activity which is important for cognitive task performance is related to an increase of patients age

  16. Visual and SPM Analysis of Brain Perfusion SPECT in Patients of Dementia with Lewy Bodies with Clinical Correlation

    International Nuclear Information System (INIS)

    Kang, Do Young; Park, Kyung Won; Kim, Jae Woo

    2003-01-01

    Dementia with Lewy bodies (DLB) is widely recognized as the second commonest form of degenerative dementia. Its core clinical features include persistent visual hallucinosis, fluctuating cognitive impairment and parkinsonism. We evaluated the brain perfusion of dementia with Lewy bodies by SPM analysis and correlated the findings with clinical symptom. Twelve DLB patients (mean age ; 68.88.3 yrs, K-MMSE ; 17.36) and 30 control subjects (mean age ; 60.17.7 yrs) were included. Control subjects were selected by 28 items of exclusion criteria and checked by brain CT or MRI except 3 subjects. Tc-99m HMPAO brain perfusion SPECT was performed and the image data were analyzed by visual interpretation and SPM99 as routine protocol. In visual analysis, 7 patients showed hypoperfusion in both frontal, temporal, parietal and occipital lobe, 2 patients in both frontal, temporal and parietal lobe, 2 patients in both temporal, parietal and occipital lobe, 1 patients in left temporal, parietal and occipital lobe. In SPM analysis (uncorrected p<0.01), significant hypoperfusion was shown in Lt inf. frontal gyrus (B no.47), both inf. parietal lobule (Rt B no.40), Rt parietal lobe (precuneus), both sup. temporal gyrus (Rt B no.42), Rt mid temporal gyrus, Lt transverse temporal gyrus (B no.41), both para hippocampal gyrus, Rt thalamus (pulvinar), both cingulate gyrus (Lt B no.24, Lt B no.25, Rt B no.23, Rt B no.24, Rt B no.33), Rt caudate body, both occipital lobe (cuneus, Lt B no.17, Rt B no.18). All patients had fluctuating cognition and parkinsonism, and 9 patients had visual hallucination. The result of SPM analysis was well correlated with visual interpretation and may be helpful to specify location to correlate with clinical symptom. Significant perfusion deficits in occipital region including visual cortex and visual association area are characteristic findings in DLB. Abnormalities in these areas may be important in understanding symptoms of visual hallucination and

  17. Visual and SPM Analysis of Brain Perfusion SPECT in Patients of Dementia with Lewy Bodies with Clinical Correlation

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Do Young; Park, Kyung Won; Kim, Jae Woo [College of Medicine, Univ. of Donga, Busan (Korea, Republic of)

    2003-07-01

    Dementia with Lewy bodies (DLB) is widely recognized as the second commonest form of degenerative dementia. Its core clinical features include persistent visual hallucinosis, fluctuating cognitive impairment and parkinsonism. We evaluated the brain perfusion of dementia with Lewy bodies by SPM analysis and correlated the findings with clinical symptom. Twelve DLB patients (mean age ; 68.88.3 yrs, K-MMSE ; 17.36) and 30 control subjects (mean age ; 60.17.7 yrs) were included. Control subjects were selected by 28 items of exclusion criteria and checked by brain CT or MRI except 3 subjects. Tc-99m HMPAO brain perfusion SPECT was performed and the image data were analyzed by visual interpretation and SPM99 as routine protocol. In visual analysis, 7 patients showed hypoperfusion in both frontal, temporal, parietal and occipital lobe, 2 patients in both frontal, temporal and parietal lobe, 2 patients in both temporal, parietal and occipital lobe, 1 patients in left temporal, parietal and occipital lobe. In SPM analysis (uncorrected p<0.01), significant hypoperfusion was shown in Lt inf. frontal gyrus (B no.47), both inf. parietal lobule (Rt B no.40), Rt parietal lobe (precuneus), both sup. temporal gyrus (Rt B no.42), Rt mid temporal gyrus, Lt transverse temporal gyrus (B no.41), both para hippocampal gyrus, Rt thalamus (pulvinar), both cingulate gyrus (Lt B no.24, Lt B no.25, Rt B no.23, Rt B no.24, Rt B no.33), Rt caudate body, both occipital lobe (cuneus, Lt B no.17, Rt B no.18). All patients had fluctuating cognition and parkinsonism, and 9 patients had visual hallucination. The result of SPM analysis was well correlated with visual interpretation and may be helpful to specify location to correlate with clinical symptom. Significant perfusion deficits in occipital region including visual cortex and visual association area are characteristic findings in DLB. Abnormalities in these areas may be important in understanding symptoms of visual hallucination and

  18. fMRat: an extension of SPM for a fully automatic analysis of rodent brain functional magnetic resonance series.

    Science.gov (United States)

    Chavarrías, Cristina; García-Vázquez, Verónica; Alemán-Gómez, Yasser; Montesinos, Paula; Pascau, Javier; Desco, Manuel

    2016-05-01

    The purpose of this study was to develop a multi-platform automatic software tool for full processing of fMRI rodent studies. Existing tools require the usage of several different plug-ins, a significant user interaction and/or programming skills. Based on a user-friendly interface, the tool provides statistical parametric brain maps (t and Z) and percentage of signal change for user-provided regions of interest. The tool is coded in MATLAB (MathWorks(®)) and implemented as a plug-in for SPM (Statistical Parametric Mapping, the Wellcome Trust Centre for Neuroimaging). The automatic pipeline loads default parameters that are appropriate for preclinical studies and processes multiple subjects in batch mode (from images in either Nifti or raw Bruker format). In advanced mode, all processing steps can be selected or deselected and executed independently. Processing parameters and workflow were optimized for rat studies and assessed using 460 male-rat fMRI series on which we tested five smoothing kernel sizes and three different hemodynamic models. A smoothing kernel of FWHM = 1.2 mm (four times the voxel size) yielded the highest t values at the somatosensorial primary cortex, and a boxcar response function provided the lowest residual variance after fitting. fMRat offers the features of a thorough SPM-based analysis combined with the functionality of several SPM extensions in a single automatic pipeline with a user-friendly interface. The code and sample images can be downloaded from https://github.com/HGGM-LIM/fmrat .

  19. SPM analysis of brain perfusion SPECT and F-18 FDG PET in the Korean autosomal dominant nocturnal frontal lobe epilepsy family

    International Nuclear Information System (INIS)

    Won, Kyoung Sook; Zeon, Seok Kil

    2004-01-01

    This study attempted to investigate the specific pattern of brain perfusion and glucose metabolism in the Korean autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) family. Using Tc-99m ECD brain perfusion SPECT. we assessed brain perfusion in 6 patients at interictal period and 5 patients at ictal period. Interictal F-18 FDG PET was performed on 6 affected family members. The scans were statistically analyzed by using statistical parametric mapping (SPM99). The data of the affected family members were compared to those of the control subjects. Interictal F-18 FDG PET SPM group analysis showed decreased glucose metabolism over the left middle and superior frontal gyri and the left central regions including the anterior parietal lobe. There was a less pronounced decrease in glucose uptake in the right anterior superior frontal gyrus. Interictal brain perfusion SPECT SPM group analysis showed similar pattern of decreased perfusion compared to those of interictal F-18 FDG PET. Ictal brain perfusion SPECT SPM group analysis revealed increased perfusion over the left pre-and postcentral gyri and less pronounced increased perfusion in the right postcentral gyrus. lnterictal F -18 PET and brain perfusion SPECT SPM group analysis suggest that major abnormalities of ADNFLE family are in the left frontal lobe. These findings may be helpful to elucidate the pathophysiological mechanism of this rare disease entity

  20. Characteristics of Cerebral Blood Flow in Vascular Dementia using SPM Analysis Compared to Normal Control and Alzheimer's Dementia

    International Nuclear Information System (INIS)

    Kang, Do Young; Park, Kyung Won; Kim, Jae Woo

    2003-01-01

    Cerebral perfusion pattern of vascular dementia (VD) was not well established and overlap of cerebral perfusion pattern was reported between VD and Alzheimer's dementia (AD). The aim of this study is to assess the specific patterns of SPECT finding in VD compared with normal control subjects and to disclose differences of cerebral blood flow between subjects with VD and AD were investigated using statistic parametric mapping analysis. Thirty-two VD (mean age ; 67.86.4 years, mean CDR ; 0.980.27), 51 AD (mean age ; 71.47.2 years, CDR ; 1.160.47), which were matched for age and severity of dementia, and 30 normal control subjects (mean age ; 60.17.7 years) participated in this study. The Tc-99m HMPAO brain perfusion SPECT data were analyzed by SPM99. The SPECT data of the patients with VD were compared to those of the control subjects and then compared to the patients with AD. SPM analysis of the SPECT image showed significant perfusion deficits in the both frontal (both cingulate gyrus, both inferior frontal gyrus, B no.47, right frontal rectal gyrus, left frontal subcallosal gyrus, B no.25), both temporal (right insula, B no.13, left superior temporal gyrus, left parahippocampal gyrus, B no.35), occipital (occipital lingual gyrus), right corpus callosum and right cerebellar tonsil regions in subjects with VD compared with normal control subjects (uncorrected p<0.01). Comparison of the two dementia groups (uncorrected p<0.01) revealed significant hypoperfusion in both parietal posterior central gyrus, right inferior frontal gyrus (B no.47), left insula, right thalamus (ventral lateral nucleus), right claustrum and right occipital cuneus regions in VD group compared with AD. There were no typical confined regional hypoperfusion areas but scattered multiple perfusion deficits in VD compared AD. These findings may be helpful to reflect the pathophysiological mechanisms of VD and to disclose differences of cerebral blood flow between subjects with VD and AD

  1. Correlation with neuropsychological assessment and SPM analysis of brain perfusion SPECT in patients with progressive supranuclear palsy

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Young Jin; Kang, Do Young; Park, Kyung Won; Kim, Jae Woo [School of Medicine, Dong-A University, Busan (Korea, Republic of)

    2004-07-01

    Progressive supranuclear palsy (PSP) is a degenerative condition of unknown aetiology that produces an akinetic-rigid form of parkinsonism characterised by early falls, dementia and abnormalities of extraocular movements. The patterns of decreased regional cerebral blood flow and cognitive impairment in PSP compared with normal control have been insufficiently investigated and a limited number of studies have been performed. We evaluated clinical symptoms, functional neuroimaging study using Tc-99m HMPAO SPECT and neuropsychological profiles in patients with PSP. Eleven patients with PSP diagnosed by the clinical criteria of National Institute of Neurological Disorders and Stroke and the Society for PSP (NINDS-SPSP) (mean age: 70.5{+-}5.6 years, educational period: 4.5{+-}4.7 years) and age-matched 10 healthy control subjects (mean age: 68.1{+-}4.5 years, educational period: 6.5{+-}4.1 years) participated in this study were participated. All patients were given a neurologic examination, brain MRI and cerebral perfusion SPECT using Tc-99m HMPAO. We concomittently evaluated several cognitive profiles using the Seoul Neuropsychological Screening Battery. SPM analysis of the SPECT image showed significant perfusion deficits in the left inferior frontal gyrus, left caudate nucleus, left middle frontal gyrus and cingulate gyrus in the patients with PSP compared with age-matched healthy control (uncorrected p<0.01). On neuropsychological assessment, cognitive deficits on verbal and visual memory, word fluency and frontal executive functions were prominent in most patients with PSP compared with healthy control subjects. Our findings suggest that measurement of regional cerebral blood flow by perfusion SPECT and voxel-based SPM analysis with neuropsychological assessment are useful to understanding the correlation between perfusion deficits and abnormal cognitive profiles in patients with PSP.

  2. SPM analysis of parametric (R)-[11C]PK11195 binding images: plasma input versus reference tissue parametric methods.

    Science.gov (United States)

    Schuitemaker, Alie; van Berckel, Bart N M; Kropholler, Marc A; Veltman, Dick J; Scheltens, Philip; Jonker, Cees; Lammertsma, Adriaan A; Boellaard, Ronald

    2007-05-01

    (R)-[11C]PK11195 has been used for quantifying cerebral microglial activation in vivo. In previous studies, both plasma input and reference tissue methods have been used, usually in combination with a region of interest (ROI) approach. Definition of ROIs, however, can be labourious and prone to interobserver variation. In addition, results are only obtained for predefined areas and (unexpected) signals in undefined areas may be missed. On the other hand, standard pharmacokinetic models are too sensitive to noise to calculate (R)-[11C]PK11195 binding on a voxel-by-voxel basis. Linearised versions of both plasma input and reference tissue models have been described, and these are more suitable for parametric imaging. The purpose of this study was to compare the performance of these plasma input and reference tissue parametric methods on the outcome of statistical parametric mapping (SPM) analysis of (R)-[11C]PK11195 binding. Dynamic (R)-[11C]PK11195 PET scans with arterial blood sampling were performed in 7 younger and 11 elderly healthy subjects. Parametric images of volume of distribution (Vd) and binding potential (BP) were generated using linearised versions of plasma input (Logan) and reference tissue (Reference Parametric Mapping) models. Images were compared at the group level using SPM with a two-sample t-test per voxel, both with and without proportional scaling. Parametric BP images without scaling provided the most sensitive framework for determining differences in (R)-[11C]PK11195 binding between younger and elderly subjects. Vd images could only demonstrate differences in (R)-[11C]PK11195 binding when analysed with proportional scaling due to intersubject variation in K1/k2 (blood-brain barrier transport and non-specific binding).

  3. Differential Features of Cerebral Perfusion in Dementia with Lewy Bodies Compared to Alzheimer's Dementia using SPM Analysis

    International Nuclear Information System (INIS)

    Kang, Do Young; Park, Kyung Won; Kim, Jae Woo

    2003-01-01

    Alzheimer's dementia (AD) and dementia with Lewy bodies (DLB) are most common cause of dementia in elderly people. Clinical distinction in some cases of DLB from AD may be difficult as symptom profiles overlap. Some neuropathologic overlap is also seen as beta-amyloidosis and senile plaques can be found in both disease. Both disease also share severe acetylcholine depletion. We evaluated the differences of brain perfusion between DLB and AD using statistical parametric mapping analysis. Twelve DLB (mean age ; 68.8±8.3 years, K-MMSE ; 17.3±6.1) and 51 AD patients (mean age ; 71.4±7.2 years, K-MMSE ; 16.7±4.5), which were matched for age and severity of dementia, participated in this study. Tc-99m HMPAO SPECT was performed for measuring regional cerebral blood flow. Statistical parametric mapping (SPM99) software was used for automatic and objective approach to analyze SPECT image data. The SPECT data of the patients with DLB were compared to patients with AD. Comparison of the two dementia groups (uncorrected p<0.01) revealed significant hypoperfusion in both occipital (both middle occipital gyrus, Rt B no. 18 and Lt cuneus), both parietal (Lt parietal precuneus, Lt B no. 39, Lt inferior parietal lobule and Rt supramarginal gyrus) lobes in DLB compared with AD. Significant hyperperfusion was noted in Rt frontal (sup. frontal gyrus, B no.10, middle frontal gyrus, B no. 9, B no. 11, inf. frontal gyrus), Rt putamen, Lt ant. cingulate gyrus (B no. 24), both cerebellar post. lobe (Lt tuber, Lt declive, Lt tonsil, Rt declive) in DLB compared with AD. We found a significant differences in the cerebral perfusion pattern between DLB and AD. Differential feature of cerebral perfusion in DLB was both occipital hypoperfusion and preserved Rt frontal perfusion compared to AD. Therefore in difficult case of clinical an neuro pathologic diagnosis, brain perfusion SPECT with SPM analysis may be helpful to differentiate DLB from AD

  4. Visual and SPM analysis of regional cerebral perfusion with Tc-99m ECD brain SPECT in patients with developmental language disorder

    International Nuclear Information System (INIS)

    Yoon, Joon Kee; Lee, Myung Hoon; Joh, Chul Woo; Yoon, Seok Nam; Oh, Eun Young

    2003-01-01

    Developmental language disorder (DLD) refers to inadequate language acquisition at the expected age in children with otherwise normal development. However, language delay can be observed in patients with other developmental disoder (ODD). We, therefore, evaluated regional cerebral perfusion pattern in patients with DLD and ODD by means of visual and SPM analysis. Twelve patients, who underwent Tc-99m ECD brain SPECT within 3 weeks of their first visit, were included in the study. Psychological and language tests classified the patients into 2 groups ; 6 with DLD (3-7 yr, 5 male and I female) and 6 with ODD (2-6 yr, 6 male). Visual analysis for regional cerebral perfusion was done in each patient. SPM with 7 controls (age=7) was performed to evaluate difference between 2 groups using t-test. P value of less than 0.005 was considered to be significant. All patients had significant language delay for their age (9 month 3.5 yr). Among 6 patients with ODD, 4 had pervasive developmental disorder, 1 mental retardation and 1 attachment disorder. Visual analysis revealed significant perfusion decrease in only 1 patient with DLD and 2 with ODD ; the regions were left parieto-temporal cortex, both frontal and cerebellar cortices, and right temporal cortex respectively. Nine of 12 patients showed normal perfusion. SPM demonstrated perfusion decrease in left inferior frontal cortex and left superior parietal cortex (Wernicke's area) in patients with DLD, while, in patients with ODD, perfusion decrease was mostly located in the right hemisphere (lateral frontoorbital gyrus, occipitotemporal gyrus, cuneus and cerebellum). Corpus callosum showed no significant perfusion abnormality in both groups. Regional cerebral perfusion of patients with DLD, which was mainly located in the speech area, is quite different from that of ODD-patients with language delay. While SPM successfully revealed this difference in perfusion pattern, visual analysis had limited value

  5. Nitrogen oxides, ozone and heavy metals analysis of suspended particulate matter (spm) of air in Nairobi, Kenya

    International Nuclear Information System (INIS)

    Odhiambo, O.; Kinyua, A.M.; Gatebe, C.K.

    2001-01-01

    Motor vehicle emissions are a major source of air pollution in most urban centers. In Kenya, Nairobi city has the highest traffic density and is therefore a particular cause for concern due to the poor maintenance standards of most vehicles plus the use of leaded gasoline. This study was carried out to determine the levels of nitrogen oxides (nox), suspended particulate matter (PM10), ozone (O3) and heavy metals in the SPM collected from the ambient air of Nairobi city. Sampling was done once every week for a period of three months (February to April 2000). Hourly average concentrations of N0 2 , NO and O3 were measured simultaneously from 9.00 am to 5.00 p.m., at a roundabout connecting two main highways (University and Uhuru) in the city. PM10 was collected using Gent Stacked Filter Unit (SFU) air sampler on nuclepore filters (0.4 and 8.0 ?m pore size for fine and coarse filters respectively) which were weighed and analysed for trace elements by Energy Dispersive X-ray Fluorescent (EDXRF) technique. Nitrogen oxides were analysed with thermo electron's Chemiluminescent nox Model 14B analyser while ozone was by using DASIBI ozone monitor, Model 1003 AH. An automatic vehicle counter was used For determining the vehicle density at the sampling point. The findings of the study show that the values obtained for Pb, Mn, Fe, Br, Zn, Cu and Ca are within the Who guidelines. Lead concentrations ranged from 0.051 to 1.106?g/m3; Fe, 0.149 to 3.154?g/m3; Mn, 0.002 to 0.526?g/m3; Cu, lower limit of detection (LLD) to 0.15?g/m3; Br, LLD to 0.43?g/m3; Zn, LLD to 0.14 ?g/m3 and Ca 2.18 to 5.389?g/m3. Concentrations of NO 2 , NO and O3 were also within the 8-hour Who limits with levels ranging from 0.011-0.976 ppm for NO, 0.001-0.2628 ppm for NO 2 and LLD-0.1258 ppm for ozone. The O3 levels were slightly higher in the afternoons when solar intensity was high especially the days with cloud cover of less than 3 Oktas. PM10 levels were, however, above the Who guidelines for most of

  6. Abnormal brain glucose metabolism and depressive mood in patients with pre-dialytic chronic kidney disease: SPM analysis of F-18 FDG positron emission tomography

    International Nuclear Information System (INIS)

    Jun, Sung Min; Song, Sang Heon; Kim, Seong Jang; Kim, Ji Hoon; Kwak, Ihm Soo; Kim, In Ju; Kim, Yong Ki

    2007-01-01

    The aim of this study was to investigate the relationship between depressive mood and pre-dialytic CKD, to localize and quantify depressive mood -related lesions in pre-dialytic CKD patients through statistical parametric mapping (SPM) analysis of brain positron emission tomography (PET), and to examine the usefulness of brain PET for early detection and proper treatment of depressive mood. Twenty one patients with stage 5 CKD and 22 healthy volunteers were analyzed by depressive mood assessment and statistical parametric mapping (SPM) analysis of 18F-FDG PET. Depressive mood assessment was done by Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). The largest clusters were areas including precentral gyrus, prefrontal cortex, and anterior cingulated cortex of left hemisphere. Other clusters were left transverse temporal gyrus, left superior temporal gyrus, right prefrontal cortex, right dorsolateral prefrontal cortex (BA 46, 44), right inferior frontal gyrus, right inferior parietal lobule, left angular gyrus. In addition, correlation was found between hypometabolized areas and HDRS scores of CKD patients in right prefrontal cortex (BA 11) and right anterior cingulated gyrus (BA 24). In conclusion, this study demonstrated specific depressive mood-related abnormal metabolic lesion. Interestingly, in CKD patients with severe depressive mood, cerebral metabolism was similar to that of MDD

  7. High-resolution brain SPECT imaging in attention deficit hyperactivity disorder children without comorbidity: quantitative analysis using statistical parametric mapping(SPM)

    International Nuclear Information System (INIS)

    Lee, Myoung Hoon; Yoon, Seok Nam; Oh, Eun Young; Chung, Young Ki; Hwang, Isaac; Lee, Jae Sung

    2002-01-01

    We examined the abnormalities of regional cerebral blood flow(rCBF) in children with attention deficit hyperactivity disorder(ADHD) without comorbidity using statistical parametric mapping(SPM) method. We used the patients with not compatible to DSM-IV diagnostic criteria of ADHD and normal rCBF pattern in visual analysis as normal control children. Tc-99m ECD brain SPECT was performed on 75 patients (M:F=64:11, 10.0±2.5y) with the DSM-IV diagnostic criteria of ADHD and 13 normal control children (M:F=9:4, 10.3±4.1y). Using SPM method, we compared patient group's SPECT images with those of 13 control subjects and measured the extent of the area with significant hypoperfusion(p<0.01) in predefined 34 cerebral regions. Only on area of left temporal lobe showed significant hypoperfusion in ADHD patients without comorbidity (n=75) compared with control subjects(n=13). (n=75, p<0.01, extent threshold=16). rCBF of left temporal area was decreased in ADHD group without comorbidity, such as tic, compared with control group

  8. High-resolution brain SPECT imaging in attention deficit hyperactivity disorder children without comorbidity: quantitative analysis using statistical parametric mapping(SPM)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myoung Hoon; Yoon, Seok Nam; Oh, Eun Young [Ajou University School of Medicine, Suwon (Korea, Republic of); Chung, Young Ki; Hwang, Isaac; Lee, Jae Sung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2002-07-01

    We examined the abnormalities of regional cerebral blood flow(rCBF) in children with attention deficit hyperactivity disorder(ADHD) without comorbidity using statistical parametric mapping(SPM) method. We used the patients with not compatible to DSM-IV diagnostic criteria of ADHD and normal rCBF pattern in visual analysis as normal control children. Tc-99m ECD brain SPECT was performed on 75 patients (M:F=64:11, 10.0{+-}2.5y) with the DSM-IV diagnostic criteria of ADHD and 13 normal control children (M:F=9:4, 10.3{+-}4.1y). Using SPM method, we compared patient group's SPECT images with those of 13 control subjects and measured the extent of the area with significant hypoperfusion(p<0.01) in predefined 34 cerebral regions. Only on area of left temporal lobe showed significant hypoperfusion in ADHD patients without comorbidity (n=75) compared with control subjects(n=13). (n=75, p<0.01, extent threshold=16). rCBF of left temporal area was decreased in ADHD group without comorbidity, such as tic, compared with control group.

  9. The feasibility of white matter volume reduction analysis using SPM8 plus DARTEL for the diagnosis of patients with clinically diagnosed corticobasal syndrome and Richardson's syndrome.

    Science.gov (United States)

    Sakurai, Keita; Imabayashi, Etsuko; Tokumaru, Aya M; Hasebe, Shin; Murayama, Shigeo; Morimoto, Satoru; Kanemaru, Kazutomi; Takao, Masaki; Shibamoto, Yuta; Matsukawa, Noriyuki

    2015-01-01

    Diagnosing corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) is often difficult due to the wide variety of symptoms and overlaps in the similar clinical courses and neurological findings. The purpose of this study was to evaluate the utility of white matter (WM) atrophy for the diagnosis of patients with clinically diagnosed CBD (corticobasal syndrome, CBS) and PSP (Richardson's syndrome, RS). We randomly divided the 3D T1-weighted MR images of 18 CBS patients, 33 RS patients, and 32 age-matched controls into two groups. We obtained segmented WM images in the first group using Voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) based on statistical parametric mapping (SPM) 8 plus diffeomorphic anatomical registration through exponentiated Lie algebra. A target volume of interest (VOI) for disease-specific atrophy was subsequently determined in this group using SPM8 group analyses of WM atrophy between patients groups and controls. We then evaluated the utility of these VOIs for diagnosing CBS and RS patients in the second group. Z score values in these VOIs were used as the determinant in receiver operating characteristic (ROC) analyses. Specific target VOIs were determined in the bilateral frontal subcortical WM for CBS and in the midbrain tegmentum for RS. In ROC analyses, the target VOIs of CBS and RS compared to those of controls exhibited an area under curve (AUC) of 0.99 and 0.84, respectively, which indicated an adequate diagnostic power. The VOI of CBS revealed a higher AUC than that of RS for differentiating between CBS and RS (AUC, 0.75 vs 0.53). Bilateral frontal WM volume reduction demonstrated a higher power for differentiating CBS from RS. This VOI analysis is useful for clinically diagnosing CBS and RS.

  10. SPM43.1 contributes to acid-resistance of non-symplasmata-forming cells in Pantoea agglomerans YS19.

    Science.gov (United States)

    Li, Qianqian; Miao, Yuxuan; Yi, Ting; Zhou, Jia; Lu, Zhenyue; Feng, Yongjun

    2012-03-01

    Pantoea agglomerans YS19 is a rice endophytic bacterium characterized to form multicellular biofilm-like structures called symplasmata. Phenotypic distinctions between symplasmata-forming cells and planktonic cells are crucial for understanding YS19's survival strategies. In this study, a 43.1 kDa protein SPM43.1 was identified to show significant resistance to the aggregation effect caused by denaturing acidic conditions. MALDI-TOF analysis data indicated that it is a maltose-binding protein homolog while contains sequence homologous to the chaperone protein, ClpB. The purified SPM43.1 protein was detected to exhibit chaperone-like activities at acidic conditions, where its conformation transformed from an ordered to a globally less ordered structure as revealed by circular dichroism spectroscopy, showing a similar property to most chaperone proteins. The expression of SPM43.1 in YS19 is initiated when bacterial cells begin to aggregate, yet its amount in planktonic cells greatly exceeds that in symplasmata-forming cells, suggesting its crucial role to the survival of planktonic cells in experiencing environmental fluctuations. However, the bacterium prefers to form symplasmata, while not to express SPM43.1 proteins, for surviving the artificially set fluctuant (acid here) environments. This study provides valuable information on the life styles and survival strategies of microorganisms that forms multicellular aggregates at specific growth stages.

  11. Characterisation of urban catchment suspended particulate matter (Auckland region, New Zealand); a comparison with non-urban SPM.

    Science.gov (United States)

    Bibby, Rebecca L; Webster-Brown, Jenny G

    2005-05-01

    Suspended particulate matter (SPM) is an important transport agent for metal contaminants in streams, particularly during high flow periods such as storm events. For highly contaminated urban catchments in the greater Auckland (New Zealand) area, trace metal partitioning between the dissolved phase and SPM was determined, and SPM characterised in terms of its Si, Al, Fe, Mn, Zn, Cu, Pb, TOC, TON and PO(4) concentrations, as well as particle size, abundance, type and surface area. This data was compared to similar data from representative non-urban catchments in the Auckland region, the Kaipara River and Waikato River catchments, to identify any significant differences in the SPM and its potential trace metal adsorption capacity. Trace metal partitioning was assessed by way of a distribution coefficient: K(D)=[Me(SPM)]/[Me(DISS)]. Auckland urban SPM comprises quartz, feldspars and clay minerals, with Fe-oxides and minor Mn-oxides. No particles of anthropogenic origin, other than glass shards, were observed. No change in urban SPM particle size or SSA was observed with seasonal change in temperature, but the nature of the SPM was observed to change with flow regime. The abundance of finer particles, SSA and Al content of the SPM increased under moderate flow conditions; however, Si/Al ratios remained constant, confirming the importance of aluminosilicate detrital minerals in surface run-off. The SPM Fe content was observed to decrease with increased flow and was attributed to dilution of SPM Fe-oxide of groundwater origin. The Kaipara River SPM was found to be mineralogically, chemically and biologically similar to the urban SPM. However, major differences between urban catchment SPM and SPM from the much larger (non-urban) Waikato River were observed, and attributed to a higher abundance of diatoms. The Fe content of the Waikato River SPM was consistently lower (<5%), and the Si/Al ratio and Mn content was higher. Such differences observed between urban and non

  12. Metabolic connectivity by interregional correlation analysis using statistical parametric mapping (SPM) and FDG brain PET; methodological development and patterns of metabolic connectivity in adults

    International Nuclear Information System (INIS)

    Lee, Dong Soo; Oh, Jungsu S.; Lee, Jae Sung; Lee, Myung Chul; Kang, Hyejin; Kim, Heejung; Park, Hyojin

    2008-01-01

    Regionally connected areas of the resting brain can be detected by fluorodeoxyglucose-positron emission tomography (FDG-PET). Voxel-wise metabolic connectivity was examined, and normative data were established by performing interregional correlation analysis on statistical parametric mapping of FDG-PET data. Characteristics of seed volumes of interest (VOIs) as functional brain units were represented by their locations, sizes, and the independent methods of their determination. Seed brain areas were identified as population-based gyral VOIs (n=70) or as population-based cytoarchitectonic Brodmann areas (BA; n=28). FDG uptakes in these areas were used as independent variables in a general linear model to search for voxels correlated with average seed VOI counts. Positive correlations were searched in entire brain areas. In normal adults, one third of gyral VOIs yielded correlations that were confined to themselves, but in the others, correlated voxels extended to adjacent areas and/or contralateral homologous regions. In tens of these latter areas with extensive connectivity, correlated voxels were found across midline, and asymmetry was observed in the patterns of connectivity of left and right homologous seed VOIs. Most of the available BAs yielded correlations reaching contralateral homologous regions and/or neighboring areas. Extents of metabolic connectivity were not found to be related to seed VOI size or to the methods used to define seed VOIs. These findings indicate that patterns of metabolic connectivity of functional brain units depend on their regional locations. We propose that interregional correlation analysis of FDG-PET data offers a means of examining voxel-wise regional metabolic connectivity of the resting human brain. (orig.)

  13. Metabolic connectivity by interregional correlation analysis using statistical parametric mapping (SPM) and FDG brain PET; methodological development and patterns of metabolic connectivity in adults

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Dong Soo; Oh, Jungsu S.; Lee, Jae Sung; Lee, Myung Chul [Seoul National University, College of Medicine, Department of Nuclear Medicine, Jongno-gu, Seoul (Korea); Kang, Hyejin [Seoul National University, College of Medicine, Department of Nuclear Medicine, Jongno-gu, Seoul (Korea); Seoul National University, Programs in Brain and Neuroscience, Seoul (Korea); Kim, Heejung; Park, Hyojin [Seoul National University, College of Medicine, Department of Nuclear Medicine, Jongno-gu, Seoul (Korea); Seoul National University, Interdisciplinary Program in Cognitive Science, Seoul (Korea)

    2008-09-15

    Regionally connected areas of the resting brain can be detected by fluorodeoxyglucose-positron emission tomography (FDG-PET). Voxel-wise metabolic connectivity was examined, and normative data were established by performing interregional correlation analysis on statistical parametric mapping of FDG-PET data. Characteristics of seed volumes of interest (VOIs) as functional brain units were represented by their locations, sizes, and the independent methods of their determination. Seed brain areas were identified as population-based gyral VOIs (n=70) or as population-based cytoarchitectonic Brodmann areas (BA; n=28). FDG uptakes in these areas were used as independent variables in a general linear model to search for voxels correlated with average seed VOI counts. Positive correlations were searched in entire brain areas. In normal adults, one third of gyral VOIs yielded correlations that were confined to themselves, but in the others, correlated voxels extended to adjacent areas and/or contralateral homologous regions. In tens of these latter areas with extensive connectivity, correlated voxels were found across midline, and asymmetry was observed in the patterns of connectivity of left and right homologous seed VOIs. Most of the available BAs yielded correlations reaching contralateral homologous regions and/or neighboring areas. Extents of metabolic connectivity were not found to be related to seed VOI size or to the methods used to define seed VOIs. These findings indicate that patterns of metabolic connectivity of functional brain units depend on their regional locations. We propose that interregional correlation analysis of FDG-PET data offers a means of examining voxel-wise regional metabolic connectivity of the resting human brain. (orig.)

  14. High Speed SPM of Functional Materials

    Energy Technology Data Exchange (ETDEWEB)

    Huey, Bryan D. [Univ. of Connecticut, Storrs, CT (United States)

    2015-08-14

    The development and optimization of applications comprising functional materials necessitates a thorough understanding of their static and dynamic properties and performance at the nanoscale. Leveraging High Speed SPM and concepts enabled by it, efficient measurements and maps with nanoscale and nanosecond temporal resolution are uniquely feasible. This includes recent enhancements for topographic, conductivity, ferroelectric, and piezoelectric properties as originally proposed, as well as newly developed methods or improvements to AFM-based mechanical, friction, thermal, and photoconductivity measurements. The results of this work reveal fundamental mechanisms of operation, and suggest new approaches for improving the ultimate speed and/or efficiency, of data storage systems, magnetic-electric sensors, and solar cells.

  15. Analysis of simulataneous I-123-IPT/Tc-99m-HMPAO dual isotope brain SPECT in Parkinson's disease and normal volunteers using SPM

    International Nuclear Information System (INIS)

    Chung, Y. A.; Juh, R. H.; Kim, S. H.; Park, Y. H.; Lee, S. Y.; Sohn, H. S.; Chung, S. K.

    2002-01-01

    The basal ganglia are usually poorly delineated in Parkinson's diseases on IPT images. We have studied simultaneous dual isotope brain SPECTs using I-123-IPT and Tc-99m-HMPAO, in order to overcome this limitation of IPT imaging. 17 patients (M: 7, F: 10) with Parkinson's disease (Idiopathic parkison's disease: 12, Multiple system atrophy: 5) and 4 normal volunteers (N) underwent the dual isotope brain SPECT following simultaneously injection of 370 MBq Tc-99m-HMPAO (energy window: 130-146 keV) and 111 MBq I-123-IPT (energy window: 152-168 keV). We first obtained parameters of spatial normalization during spatial normalization of Tc-99m-HMPAO brain SPECT using SPECT template. Using these parameters, we could spatially normalized I-123-IPT brain PSECT to standard space, because these images were obtained simultaneously. The difference between each groups(N vs IPD, N vs MSA, IPD vs MSA) were compared with t-test (p<0.01). We demonstrated decreased perfusion in the head and body caudate and globus pallidus on MSA compared with IPD. No significant hypo- and hyperperfusion area was observed in the other analysis. The method proposed in this study can effectively evaluate the dopamine function, and is easily applicable to conventional gamma camera system with any dual energy window acquisition modes

  16. SPM nanolithography of hydroxy-silicates

    International Nuclear Information System (INIS)

    Valdrè, G; Moro, D; Hounsome, C M; Antognozzi, M

    2012-01-01

    Bio-nanopatterning of surfaces is becoming a crucial technique with applications ranging from molecular and cell biology to medicine. Scanning probe microscopy (SPM) is one of the most useful tools for nanopatterning of flat surfaces. However, these patterns are usually built on homogeneous surfaces and require chemical functionalization to ensure specific affinity. Layered magnesium–aluminum hydroxide–silicates have already shown unique self-assembly properties on DNA molecules, due to their peculiar crystal chemistry based on alternating positive and negative crystal layers. However, patterns on these surfaces tend to be randomly organized. Here we show etching and oxidation at the nanometer scale of magnesium–aluminum hydroxide–silicates using the same SPM probe for the creation of organized nanopatterns. In particular, it is possible to produce three-dimensional structures in a reproducible way, with a depth resolution of 0.4 nm, lateral resolution of tens of nm, and a speed of about 10 μm s −1 . We report, as an example, the construction of an atomically flat charged pattern, designed to guide DNA deposition along predetermined directions without the need of any chemical functionalization of the surface. (paper)

  17. Spontaneous Swallowing Frequency [Has Potential to] Identify Dysphagia in Acute Stroke

    Science.gov (United States)

    Carnaby, Giselle D; Sia, Isaac; Khanna, Anna; Waters, Michael

    2014-01-01

    Background and Purpose Spontaneous swallowing frequency has been described as an index of dysphagia in various health conditions. This study evaluated the potential of spontaneous swallow frequency analysis as a screening protocol for dysphagia in acute stroke. Methods In a cohort of 63 acute stroke cases swallow frequency rates (swallows per minute: SPM) were compared to stroke and swallow severity indices, age, time from stroke to assessment, and consciousness level. Mean differences in SPM were compared between patients with vs. without clinically significant dysphagia. ROC analysis was used to identify the optimal threshold in SPM which was compared to a validated clinical dysphagia examination for identification of dysphagia cases. Time series analysis was employed to identify the minimally adequate time period to complete spontaneous swallow frequency analysis. Results SPM correlated significantly with stroke and swallow severity indices but not with age, time from stroke onset, or consciousness level. Patients with dysphagia demonstrated significantly lower SPM rates. SPM differed by dysphagia severity. ROC analysis yielded a threshold of SPM ≤ 0.40 which identified dysphagia (per the criterion referent) with 0.96 sensitivity, 0.68 specificity, and 0.96 negative predictive value. Time series analysis indicated that a 5 to 10 minute sampling window was sufficient to calculate spontaneous swallow frequency to identify dysphagia cases in acute stroke. Conclusions Spontaneous swallowing frequency presents high potential to screen for dysphagia in acute stroke without the need for trained, available personnel. PMID:24149008

  18. The need of appropriate brain SPECT templates for SPM comparisons

    International Nuclear Information System (INIS)

    Morbelli, S.; Altrinetti, V.; Piccardo, A.; Rodriguez, G.; Brugnolo, A.; Nobili, F.; Mignone, A.; Pupi, A.; Koulibaly, P.M.

    2008-01-01

    Statistical parametric mapping (SPM) is used worldwide to compare brain perfusion single photon emission computed tomography (SPECT) data. The default template within the SPM package used for SPECT image normalization includes images of a group of healthy subjects studied with 99m TcHMPAO. Since [ 99m Tc] HMPAO and [ 99m Tc] ECD have shown to distribute differently in SPECT studies, we formulated the hypothesis that comparing set of [ 99m Tc]ECD data normalized by means of a [ 99m Tc]HMPAO template may lead to incorrect results. A customized [ 99m Tc]ECD template was built with SPECT and magnetic resonance imaging (MRI) images of 22 neurologically healthy women. Then, two sets of subjects, i.e. a group of patients with very early Alzheimer's disease (eAD) and a matched control group, studied by means of [ 99m Tc]ECD SPECT, were chosen for comparisons. The same statistical approach (t-test between eAD patients and controls and correlation analysis between brain SPECT and a cognitive score) was applied twice, i.e. after normalization with either the default [ 99m Tc]HMPAO template or the customized [ 99m Tc]ECD template. In the comparison between eAD and controls, a cluster of difference in the posterior-cingulate gyrus of both hemispheres was only highlighted when using the customized [ 99m Tc]ECD template, but was missed when using the default [ 99m Tc]HMPAO template. In the correlation between brain perfusion and a cognitive score, the significant cluster was more significant and far more extended, also including the right superior temporal gyrus, using the customized [ 99m Tc]ECD template than using the default [ 99m Tc]HMPAO template. These data suggest the need of customized, radiopharmaceutical-matched SPECT templates to be used within the SPM package. The present customized [ 99m Tc]ECD template is now freely available on the web. (authors)

  19. High mortality of bloodstream infection outbreak caused by carbapenem-resistant P. aeruginosa producing SPM-1 in a bone marrow transplant unit.

    Science.gov (United States)

    Chaves, Lucas; Tomich, Lísia Moura; Salomão, Matias; Leite, Gleice Cristina; Ramos, Jessica; Martins, Roberta Ruedas; Rizek, Camila; Neves, Patricia; Batista, Marjorie Vieira; Amigo, Ulysses; Guimaraes, Thais; Levin, Anna Sara; Costa, Silvia Figueiredo

    2017-12-01

    Carbapenem resistance in P. aeruginosa is increasing worldwide. In Brazil, SPM-1 is the main P. aeruginosa carbapenemase identified. Little is known about the virulence factor in SPM-1 clones.Methodolgy. We describe a carbapenem-resistant P. aeruginosa bloodstream infection (CRPa-BSI) outbreak in a bone marrow transplant Unit (BMT). Twenty-nine CRPa-BSI cases were compared to 58 controls. Microbiological characteristics of isolates, such as sensitivity, carbapenemase gene PCR for P. aeruginosa, and PFGE are described, as well as the whole-genome sequence (WGS) of three strains.Results/Key findings. The cultures from environmental and healthcare workers were negative. Some isolates harboured KPC and SPM. The WGS showed that the 03 strains belonged to ST277, presented the same mutations in outer membrane protein, efflux pump, and virulence genes such as those involved in adhesion, biofilm, quorum-sensing and the type III secretion system, but differ regarding the carbapenemase profile. A predominant clone-producing SPM harbouring Tn 4371 was identified and showed cross-transmission; no common source was found. Overall mortality rate among cases was 79 %. The first multivariate analysis model showed that neutropenia (P=0.018), GVHD prophylaxis (P=0.016) and prior use of carbapenems (P=0.0089) were associated with CRPa-BSI. However, when MASCC>21 points and platelets were added in the final multivariate analysis, only prior use of carbapenems remained as an independent risk factor for CRPa-BSI (P=0.043). The predominant clone belonging to ST277 showed high mortality. Carbapenem use was the only risk factor associated with CRPa-BSI. This finding is a wake-up call for the need to improve management in BMT units.

  20. Quantitative Comparison of SPM, FSL, and Brainsuite for Brain MR Image Segmentation

    Directory of Open Access Journals (Sweden)

    Kazemi K

    2014-03-01

    Full Text Available Background: Accurate brain tissue segmentation from magnetic resonance (MR images is an important step in analysis of cerebral images. There are software packages which are used for brain segmentation. These packages usually contain a set of skull stripping, intensity non-uniformity (bias correction and segmentation routines. Thus, assessment of the quality of the segmented gray matter (GM, white matter (WM and cerebrospinal fluid (CSF is needed for the neuroimaging applications. Methods: In this paper, performance evaluation of three widely used brain segmentation software packages SPM8, FSL and Brainsuite is presented. Segmentation with SPM8 has been performed in three frameworks: i default segmentation, ii SPM8 New-segmentation and iii modified version using hidden Markov random field as implemented in SPM8-VBM toolbox. Results: The accuracy of the segmented GM, WM and CSF and the robustness of the tools against changes of image quality has been assessed using Brainweb simulated MR images and IBSR real MR images. The calculated similarity between the segmented tissues using different tools and corresponding ground truth shows variations in segmentation results. Conclusion: A few studies has investigated GM, WM and CSF segmentation. In these studies, the skull stripping and bias correction are performed separately and they just evaluated the segmentation. Thus, in this study, assessment of complete segmentation framework consisting of pre-processing and segmentation of these packages is performed. The obtained results can assist the users in choosing an appropriate segmentation software package for the neuroimaging application of interest.

  1. Study of regional cerebral blood flow in obsessive compulsive disorder patients with SPM and ROI method

    International Nuclear Information System (INIS)

    Li Peiyong; Jiang Xufeng; Zhang Liying; Guo Wanhua; Zhu Chengmo

    2002-01-01

    Objective: To investigate the alternations in regional cerebral blood flow (rCBF) in obsessive compulsive disorder (OCD) patients using statistical parametric mapping (SPM). Methods: rCBF measurements using 99 Tc m -ethyl cysteinate dimer (ECD) SPECT was performed on 14 OCD patients and 23 age-matched healthy volunteers. The rCBF distribution was compared between these two groups with SPM under the conditions of increased and decreased perfusion, and with regions of interest (ROIs) using cerebral template. P value was set at 0.01 level. Results: SPM analysis showed that rCBF decreased in cerebral areas including bilateral putamen, superior temporal gyrus and precuneus, and right orbital gyrus, superior and middle frontal gyrus, and left temporo-occipital lobule and superior parietal gyrus, and vermis. rCBF was also increased in left inferior frontal gyrus and posterior cingulate gyrus. With ROIs method, rCBF was decreased in right anterior frontal, temporo-parietal lobule and left temporo-occipital lobule. Conclusions: The study supports the viewpoint that rCBF abnormality of fronto-striatal circuits is involved in OCD patients. SPM method is a forceful tool in analyzing cerebral regional characters

  2. Spontaneous swallowing frequency has potential to identify dysphagia in acute stroke.

    Science.gov (United States)

    Crary, Michael A; Carnaby, Giselle D; Sia, Isaac; Khanna, Anna; Waters, Michael F

    2013-12-01

    Spontaneous swallowing frequency has been described as an index of dysphagia in various health conditions. This study evaluated the potential of spontaneous swallow frequency analysis as a screening protocol for dysphagia in acute stroke. In a cohort of 63 acute stroke cases, swallow frequency rates (swallows per minute [SPM]) were compared with stroke and swallow severity indices, age, time from stroke to assessment, and consciousness level. Mean differences in SPM were compared between patients with versus without clinically significant dysphagia. Receiver operating characteristic curve analysis was used to identify the optimal threshold in SPM, which was compared with a validated clinical dysphagia examination for identification of dysphagia cases. Time series analysis was used to identify the minimally adequate time period to complete spontaneous swallow frequency analysis. SPM correlated significantly with stroke and swallow severity indices but not with age, time from stroke onset, or consciousness level. Patients with dysphagia demonstrated significantly lower SPM rates. SPM differed by dysphagia severity. Receiver operating characteristic curve analysis yielded a threshold of SPM≤0.40 that identified dysphagia (per the criterion referent) with 0.96 sensitivity, 0.68 specificity, and 0.96 negative predictive value. Time series analysis indicated that a 5- to 10-minute sampling window was sufficient to calculate spontaneous swallow frequency to identify dysphagia cases in acute stroke. Spontaneous swallowing frequency presents high potential to screen for dysphagia in acute stroke without the need for trained, available personnel.

  3. Investigation of SPM in WDM System with EDFA

    Directory of Open Access Journals (Sweden)

    Tomáš Ivaniga

    2016-12-01

    Full Text Available The article describes a nonlinear phenomenon SPM (Self Phase Modulation, which occurs in the all-optical communications systems. In the 21st century, the WDM (Wavelength Division Multiplex system cannot be created without the software that simulates the system under real conditions. The most important WDM components include the EDFA (Erbium Doped Fiber Amplifier, in which amplification occurs at all wavelengths. The 10 Gbps optical line DWDM (Dense Wavelength Division Multiplex system is created according to the ITU-T.G.694.1, in which the SPM phenomenon is observed.

  4. Comparison of normal adult and children brain SPECT imaging using statistical parametric mapping(SPM)

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Myoung Hoon; Yoon, Seok Nam; Joh, Chul Woo; Lee, Dong Soo [Ajou University School of Medicine, Suwon (Korea, Republic of); Lee, Jae Sung [Seoul national University College of Medicine, Seoul (Korea, Republic of)

    2002-07-01

    This study compared rCBF pattern in normal adult and normal children using statistical parametric mapping (SPM). The purpose of this study was to determine distribution pattern not seen visual analysis in both groups. Tc-99m ECD brain SPECT was performed in 12 normal adults (M:F=11:1, average age 35 year old) and 6 normal control children (M:F=4:2, 10.5{+-}3.1y) who visited psychiatry clinic to evaluate ADHD. Their brain SPECT revealed normal rCBF pattern in visual analysis and they were diagnosed clinically normal. Using SPM method, we compared normal adult group's SPECT images with those of 6 normal children subjects and measured the extent of the area with significant hypoperfusion and hyperperfusion (p<0.001, extent threshold=16). The areas of both angnlar gyrus, both postcentral gyrus, both superior frontal gyrus, and both superior parietal lobe showed significant hyperperfusion in normal adult group compared with normal children group. The areas of left amygdala gyrus, brain stem, both cerebellum, left globus pallidus, both hippocampal formations, both parahippocampal gyrus, both thalamus, both uncus, both lateral and medial occipitotemporal gyrus revealed significantly hyperperfusion in the children. These results demonstrated that SPM can say more precise anatomical area difference not seen visual analysis.

  5. Comparison of normal adult and children brain SPECT imaging using statistical parametric mapping(SPM)

    International Nuclear Information System (INIS)

    Lee, Myoung Hoon; Yoon, Seok Nam; Joh, Chul Woo; Lee, Dong Soo; Lee, Jae Sung

    2002-01-01

    This study compared rCBF pattern in normal adult and normal children using statistical parametric mapping (SPM). The purpose of this study was to determine distribution pattern not seen visual analysis in both groups. Tc-99m ECD brain SPECT was performed in 12 normal adults (M:F=11:1, average age 35 year old) and 6 normal control children (M:F=4:2, 10.5±3.1y) who visited psychiatry clinic to evaluate ADHD. Their brain SPECT revealed normal rCBF pattern in visual analysis and they were diagnosed clinically normal. Using SPM method, we compared normal adult group's SPECT images with those of 6 normal children subjects and measured the extent of the area with significant hypoperfusion and hyperperfusion (p<0.001, extent threshold=16). The areas of both angnlar gyrus, both postcentral gyrus, both superior frontal gyrus, and both superior parietal lobe showed significant hyperperfusion in normal adult group compared with normal children group. The areas of left amygdala gyrus, brain stem, both cerebellum, left globus pallidus, both hippocampal formations, both parahippocampal gyrus, both thalamus, both uncus, both lateral and medial occipitotemporal gyrus revealed significantly hyperperfusion in the children. These results demonstrated that SPM can say more precise anatomical area difference not seen visual analysis

  6. The systems prioritization method (SPM) CD-ROM demonstration for Waste Management '96

    International Nuclear Information System (INIS)

    Harris, C.L.; Boak, D.M.; Prindle, N.H.; Beyeler, W.

    1996-01-01

    In March 1994, the Department of Energy Carlsbad Area Office (DOE/CAO) implemented a performance-based planning method to assist in prioritization within the Waste Isolation Pilot Plant (WIPP). Probabilistic performance calculations were required for the Systems Prioritization Method (SPM) and roughly 46,700 combinations of activities were analyzed, generating a large volume of information to be documented, analyzed, and communicated. A self-contained information management system consisting of a relational database on a 600-megabyte CD-ROM was built to meet this need. The CD-ROM was used to store performance assessment results, data analysis and visualization tools, information about the activities, electronic copies of 40 ILFR 191 and 40 CFR 268, technical reference papers, and the final SPM report. Copies of the CD-ROM were distributed to interested members of the public, WIPP participants, and the Environmental Protection Agency (EPA)

  7. Summary of the systems prioritization method (SPM) as a decision-aiding tool for the Waste Isolation Pilot Plant

    International Nuclear Information System (INIS)

    Boak, D.M.; Prindle, N.H.; Lincoln, R.; Mendenhall, F.; Weiner, R.; Bills, R.A.

    1996-01-01

    In March 1994, the Department of Energy Carlsbad Area Office (DOE/CAO) implemented a performance-based planning method to assist in programmatic prioritization within the Waste Isolation Pilot Plant (WIPP) project with respect to applicable Environmental Protection Agency (EPA) long-term performance requirements stated in 40 CFR 191.13(a) and 40 CFR 268.6. This method, the Systems Prioritization Method (SPM), was designed by Sandia National Laboratories (SNL) to: (1) identify programmatic options (activities) and their costs and durations; (2) analyze potential combinations of activities in terms of predicted contribution to long-term performance; and (3) analyze cost, duration, and performance tradeoffs. SPM results were the basis for recommendations to DOE/CAO in May 1995 for prioritization within the WIPP project. This paper presents a summary of the SPM implementation, key results, and lessons learned

  8. Nature, Origin and Transfers of SPM (Mineral, Organic, and Biological) in Hydrosystems : a New Methodological Approach by Morphogranulometry

    Science.gov (United States)

    Viennet, D.; Fournier, M.; Copard, Y.; Dupont, J. P.

    2017-12-01

    Source to sink is one of the main concepts in Earth Sciences for a better knowledge of hydrosystems dynamics. Regarding this issue, the present day challenge consists in the characterization by in-situ measurements of the nature and the origin of suspended particles matters (SPM). Few methods can fully cover such requirements and among them, the methodology using the form of particles deserves to be developed. Indeed, morphometry of particles is widely used in sedimentology to identify different sedimentary stocks, source-to-sink transport and sedimentation mechanisms. Currently, morphometry analyses are carried out by scanning electron microscope coupled to image analysis to measure various size and shape descriptors on particles like flatness, elongation, circularity, sphericity, bluntness, fractal dimension. However, complexity and time of analysis are the main limitations of this technique for a long-term monitoring of SPM transfers. Here we present an experimental morphometric approach using a morphogranulometer (a CCD camera coupled to a peristaltic pump). The camera takes pictures while the sample is circulating through a flow cell, leading to the analysis of numerous particles in a short time. The image analysis provides size and shape information discriminating various particles stocks according to their nature and origin by statistical analyses. Measurements were carried out on standard samples of particles commonly found in natural waters. The size and morphological distributions of the different mineral fractions (clay, sand, oxides etc), biologic (microalgae, pollen, etc) and organic (peat, coal, soil organic matter, etc) samples are statistically independent and can be discriminated on a 4D graph. Next step will be on field in situ measurements in a sink-spring network to understand the transfers of the particles stocks inside this simple karstic network. Such a development would be promising for the characterisation of natural hydrosystems.

  9. VBM with viscous fluid registration of grey matter segments in SPM.

    Directory of Open Access Journals (Sweden)

    João M. S. Pereira

    2013-07-01

    Full Text Available Improved registration of grey matter segments in SPM has been achieved with the DARTEL algorithm. Previous work from our group suggested, however, that such improvements may not translate to studies of clinical groups. To address the registration issue in atrophic brains, this paper relaxed the condition of diffeomorphism, central to DARTEL, and made use of a viscous fluid registration model with limited regularisation constraints to register the modulated grey matter probability maps to an intra-population template. Quantitative analysis of the registration results after the additional viscous fluid step showed no worsening of co-localisation of fiducials compared to DARTEL or unified segmentation methods, and the resulting voxel based morphometry (VBM analyses were able to better identify atrophic regions and to produce results with fewer apparent false positives. DARTEL showed great sensitivity to atrophy, but the resulting VBM maps presented broad, amorphous regions of significance that are hard to interpret. We propose that the condition of diffeomorphism is not necessary for basic VBM studies in atrophic populations, but also that it has disadvantages that must be taken into consideration before a study. The presented viscous fluid registration method is proposed for VBM studies to enhance sensitivity and localizing power.

  10. The Southern Proper Motion Program. IV. The SPM4 Catalog

    Science.gov (United States)

    Girard, Terrence M.; van Altena, William F.; Zacharias, Norbert; Vieira, Katherine; Casetti-Dinescu, Dana I.; Castillo, Danilo; Herrera, David; Lee, Young Sun; Beers, Timothy C.; Monet, David G.; López, Carlos E.

    2011-07-01

    We present the fourth installment of the Yale/San Juan Southern Proper Motion Catalog, SPM4. The SPM4 contains absolute proper motions, celestial coordinates, and B, V photometry for over 103 million stars and galaxies between the south celestial pole and -20° declination. The catalog is roughly complete to V = 17.5 and is based on photographic and CCD observations taken with the Yale Southern Observatory's double astrograph at Cesco Observatory in El Leoncito, Argentina. The proper-motion precision, for well-measured stars, is estimated to be 2-3 mas yr-1, depending on the type of second-epoch material. At the bright end, proper motions are on the International Celestial Reference System by way of Hipparcos Catalog stars, while the faint end is anchored to the inertial system using external galaxies. Systematic uncertainties in the absolute proper motions are on the order of 1 mas yr-1.

  11. SPM response to tide and river flow in the hyper-turbid Ems River

    Science.gov (United States)

    Winterwerp, Johan C.; Vroom, Julia; Wang, Zheng-B.; Krebs, Martin; Hendriks, Erik C. M.; van Maren, Dirk S.; Schrottke, Kerstin; Borgsmüller, Christine; Schöl, Andreas

    2017-05-01

    In this paper, we analyse the behaviour of fine sediments in the hyper-turbid Lower Ems River, with focus on the river's upper reaches, a stretch of about 25 km up-estuary of Terborg. Our analysis is based on long records of suspended particulate matter (SPM) from optical backscatter (OBS) measurements close to the bed at seven stations along the river, records of salinity and water level measurements at these stations, acoustic measurements on the vertical mud structure just up-estuary of Terborg and oxygen profiles in the lower 3 m of the water column close to Leerort and Terborg. Further, we use cross-sectionally averaged velocities computed with a calibrated numerical model. Distinction is made between four timescales, i.e. the semi-diurnal tidal timescale, the spring-neap tidal timescale, a timescale around an isolated peak in river flow (i.e. about 3 weeks) and a seasonal timescale. The data suggest that a pool of fluid/soft mud is present in these upper reaches, from up-estuary of Papenburg to a bit down-estuary of Terborg. Between Terborg and Gandersum, SPM values drop rapidly but remain high at a few gram per litre. The pool of fluid/soft mud is entrained/mobilized at the onset of flood, yielding SPM values of many tens gram per litre. This suspension is transported up-estuary with the flood. Around high water slack, part of the suspension settles, being remixed during ebb, while migrating down-estuary, but likely not much further than Terborg. Around low water slack, a large fraction of the sediment settles, reforming the pool of fluid mud. The rapid entrainment from the fluid mud layer after low water slack is only possible when the peak flood velocity exceeds a critical value of around 1 m/s, i.e. when the stratified water column seems to become internally supercritical. If the peak flood velocity does not reach this critical value, f.i. during neap tide, fluid mud is not entrained up to the OBS sensors. Thus, it is not classical tidal asymmetry, but

  12. Molecular epidemiology of SPM-1-producing Pseudomonas aeruginosa by rep-PCR in hospitals in Parana, Brazil.

    Science.gov (United States)

    Kalluf, K O; Arend, L N; Wuicik, T E; Pilonetto, M; Tuon, F F

    2017-04-01

    Infections caused by multidrug resistant microorganisms are a global health problem, and Pseudomonas aeruginosa is an important nosocomial pathogen, easily disseminated in the hospital environment. The aim of this study was to determine SPM-1 in P. aeruginosa strains in 30 Brazilian hospitals and the genetic similarity of isolates. We analyzed 161 isolates of carbapenem-resistant P. aeruginosa. Imipenem/EDTA and imipenem strip were used for phenotypic detection of MBL production; and real-time polymerase chain reaction (PCR) for genetic detection. Genetic similarity was determined by rep-PCR. We obtained 136/161 (84.5%) isolates with positive phenotypic result for metallo-β-lactamase (MBL) and the bla SPM-1 gene was identified in 41 isolates. There was a predominant profile (>95% of genetic similarity) in 92.7% of isolates. This predominant profile was widely disseminated in Paraná state. SPM-1 is the main MBL identified in carbapenem-resistant P. aeruginosa in Southern Brazil. The genetic similarity among some isolates suggests a clonal expansion. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Study of regional stability of 99Tcm-ECD distribution in normal brain by SPM and ROI

    International Nuclear Information System (INIS)

    Li Peiyong; Guo Wanhua; Chen Gang; Zhu Chengmo

    2001-01-01

    Objective: To quantify regional cerebral blood flow (rCBF) with repeated 99 Tc m -ECD brain SPECT. Methods: Each of thirteen normal volunteers (31.2 +- 11.8 years old) underwent 12 times of SPECT scanning 1 hour after injection of 99 Tc m -ECD, the acquisition lasted 60 minutes. The distribution of 99 Tc m -ECD in brain was analyzed by SPM and ROI method. Results: There was no difference of regional ECD distribution within 60 min in cortex, basal ganglia and thalamus showed by SPM. ROI analysis showed a very slow change of regional gray matter/white matter (G/W) over time, and the slope of the curve was almost zero. Conclusion: Regional ECD distribution is stable in normal brain. ECD clearance from brain is slow and the changes of it within 60 minutes were of no significant difference

  14. Reliability evaluation of I-123 ADAM SPECT imaging using SPM software and AAL ROI methods

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Bang-Hung [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan (China); Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan (China); Tsai, Sung-Yi [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan (China); Department of Imaging Medical, St.Martin De Porres Hospital, Chia-Yi, Taiwan (China); Wang, Shyh-Jen [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan (China); Department of Nuclear Medicine, Taipei Veterans General Hospital, Taiwan (China); Su, Tung-Ping; Chou, Yuan-Hwa [Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan (China); Chen, Chia-Chieh [Institute of Nuclear Energy Research, Longtan, Taiwan (China); Chen, Jyh-Cheng, E-mail: jcchen@ym.edu.tw [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan (China)

    2011-08-21

    The level of serotonin was regulated by serotonin transporter (SERT), which is a decisive protein in regulation of serotonin neurotransmission system. Many psychiatric disorders and therapies were also related to concentration of cerebral serotonin. I-123 ADAM was the novel radiopharmaceutical to image SERT in brain. The aim of this study was to measure reliability of SERT densities of healthy volunteers by automated anatomical labeling (AAL) method. Furthermore, we also used statistic parametric mapping (SPM) on a voxel by voxel analysis to find difference of cortex between test and retest of I-123 ADAM single photon emission computed tomography (SPECT) images. Twenty-one healthy volunteers were scanned twice with SPECT at 4 h after intravenous administration of 185 MBq of {sup 123}I-ADAM. The image matrix size was 128x128 and pixel size was 3.9 mm. All images were obtained through filtered back-projection (FBP) reconstruction algorithm. Region of interest (ROI) definition was performed based on the AAL brain template in PMOD version 2.95 software package. ROI demarcations were placed on midbrain, pons, striatum, and cerebellum. All images were spatially normalized to the SPECT MNI (Montreal Neurological Institute) templates supplied with SPM2. And each image was transformed into standard stereotactic space, which was matched to the Talairach and Tournoux atlas. Then differences across scans were statistically estimated on a voxel by voxel analysis using paired t-test (population main effect: 2 cond's, 1 scan/cond.), which was applied to compare concentration of SERT between the test and retest cerebral scans. The average of specific uptake ratio (SUR: target/cerebellum-1) of {sup 123}I-ADAM binding to SERT in midbrain was 1.78{+-}0.27, pons was 1.21{+-}0.53, and striatum was 0.79{+-}0.13. The cronbach's {alpha} of intra-class correlation coefficient (ICC) was 0.92. Besides, there was also no significant statistical finding in cerebral area using SPM2

  15. Levels of As, Pb, Cd and Fe in Suspended Particulate Matter (SPM ...

    African Journals Online (AJOL)

    Suspended Particulate Matter (SPM) collected from three different artisans' workshops was analyzed for As, Cd, Pb and Fe by Atomic Absorption Spectrophotometry (AAS). The range of SPM concentrations for the three workshops was 583-20,166Bg/m3. The highest concentrations of these elements were observed in Motor ...

  16. High-throughput parallel SPM for metrology, defect and mask inspection

    NARCIS (Netherlands)

    Sadeghian Marnani, H.; Herfst, R.W.; Dool, T.C. van den; Crowcombe, W.E.; Winters, J.; Kramers, G.F.I.J.

    2014-01-01

    Scanning probe microscopy (SPM) is a promising candidate for accurate assessment of metrology and defects on wafers and masks, however it has traditionally been too slow for high-throughput applications, although recent developments have significantly pushed the speed of SPM [1,2]. In this paper we

  17. A general XML schema and SPM toolbox for storage of neuro-imaging results and anatomical labels.

    Science.gov (United States)

    Keator, David Bryant; Gadde, Syam; Grethe, Jeffrey S; Taylor, Derek V; Potkin, Steven G

    2006-01-01

    With the increased frequency of multisite, large-scale collaborative neuro-imaging studies, the need for a general, self-documenting framework for the storage and retrieval of activation maps and anatomical labels becomes evident. To address this need, we have developed and extensible markup language (XML) schema and associated tools for the storage of neuro-imaging activation maps and anatomical labels. This schema, as part of the XML-based Clinical Experiment Data Exchange (XCEDE) schema, provides storage capabilities for analysis annotations, activation threshold parameters, and cluster and voxel-level statistics. Activation parameters contain information describing the threshold, degrees of freedom, FWHM smoothness, search volumes, voxel sizes, expected voxels per cluster, and expected number of clusters in the statistical map. Cluster and voxel statistics can be stored along with the coordinates, threshold, and anatomical label information. Multiple threshold types can be documented for a given cluster or voxel along with the uncorrected and corrected probability values. Multiple atlases can be used to generate anatomical labels and stored for each significant voxel or cluter. Additionally, a toolbox for Statistical Parametric Mapping software (http://www. fil. ion.ucl.ac.uk/spm/) was created to capture the results from activation maps using the XML schema that supports both SPM99 and SPM2 versions (http://nbirn.net/Resources/Users/ Applications/xcede/SPM_XMLTools.htm). Support for anatomical labeling is available via the Talairach Daemon (http://ric.uthscsa. edu/projects/talairachdaemon.html) and Automated Anatomical Labeling (http://www. cyceron.fr/freeware/).

  18. Identifiable Data Files - Medicare Provider Analysis and ...

    Data.gov (United States)

    U.S. Department of Health & Human Services — The Medicare Provider Analysis and Review (MEDPAR) File contains data from claims for services provided to beneficiaries admitted to Medicare certified inpatient...

  19. Identifying MMORPG Bots: A Traffic Analysis Approach

    Directory of Open Access Journals (Sweden)

    Wen-Chin Chen

    2008-11-01

    Full Text Available Massively multiplayer online role playing games (MMORPGs have become extremely popular among network gamers. Despite their success, one of MMORPG's greatest challenges is the increasing use of game bots, that is, autoplaying game clients. The use of game bots is considered unsportsmanlike and is therefore forbidden. To keep games in order, game police, played by actual human players, often patrol game zones and question suspicious players. This practice, however, is labor-intensive and ineffective. To address this problem, we analyze the traffic generated by human players versus game bots and propose general solutions to identify game bots. Taking Ragnarok Online as our subject, we study the traffic generated by human players and game bots. We find that their traffic is distinguishable by 1 the regularity in the release time of client commands, 2 the trend and magnitude of traffic burstiness in multiple time scales, and 3 the sensitivity to different network conditions. Based on these findings, we propose four strategies and two ensemble schemes to identify bots. Finally, we discuss the robustness of the proposed methods against countermeasures of bot developers, and consider a number of possible ways to manage the increasingly serious bot problem.

  20. COORDINATE-BASED META-ANALYTIC SEARCH FOR THE SPM NEUROIMAGING PIPELINE

    DEFF Research Database (Denmark)

    Wilkowski, Bartlomiej; Szewczyk, Marcin; Rasmussen, Peter Mondrup

    2009-01-01

    . BredeQuery offers a direct link from SPM5 to the Brede Database coordinate-based search engine. BredeQuery is able to ‘grab’ brain location coordinates from the SPM windows and enter them as a query for the Brede Database. Moreover, results of the query can be displayed in an SPM window and/or exported...... of the databases offer so- called coordinate-based searching to the users (e.g. Brede, BrainMap). For such search, the publications, which relate to the brain locations represented by the user coordinates, are retrieved. In this paper we present BredeQuery – a plugin for the widely used SPM5 data analytic pipeline...

  1. Comparison between the standard SPM2 template and Korean-standard template in FDG-PET

    International Nuclear Information System (INIS)

    Kim, Jung Hee; Lee, Byeong Il; Song, Ho Chun; Min, Jung Joon; Bom, Hee Seung; Lee, Jae Sung

    2005-01-01

    The preprocessing step of statistical parametric mapping (SPM) requires the procedure of spatial normalization that consists of applying the nonlinear deformations needed to force every particular PET scan to match a reference template. The purpose of this study is to asses the statistic influence of using 2 different templates (the standard SPM2-PET template and Korean-standard PET template) in the normalization. We compared the regional metabolic patterns on 18F-FDG (fluorodeoxyglucose) images obtained from 4 patients with Alzheimers disease (AD) and 16 normal subjects. The statistical outcome of between- group comparison was analyzed with SPM2 and was applied into two levels of thresholds (an uncorrected P value of P <0.001, a corrected P value of P < 0.05). As a result, the most significant hypometabolic region was commonly found in the left temporal gyrus regardless of template type or thresholds. However, inconsistent results including different extent and the t-score statistics representing metabolic changes could be also observed between two templates. While the standard SPM2 template showed hypometabolic regions corresponding to Brodman area (BA) 7 and 9, Korean-standard template was not observed these regions. In addition, hypometabolic regions corresponding to BA 38 and 46 indicated not the standard SPM2 template but Korean-standard template. Statistic result showed that the standard SPM2 template effectively reflects the dorsal region of the brain while Korean-standard template is more sensitive to the medial region of the brain

  2. Transient controls on estuarine SPM fluxes: case study in the Dee Estuary, UK.

    Science.gov (United States)

    Amoudry, Laurent; Williams, Megan; Todd, David

    2017-04-01

    Estuaries are a critical interface between land and coastal ocean across which freshwater, suspended particulate matter (SPM), and consequently terrestrial carbon, nutrients and anthropogenic contaminants are exchanged. Suspended particulate matter is closely linked to estuarine turbidity; it affects water quality and estuarine ecology; and it contributes to overall estuarine sediment budgets. However, predicting the response of estuarine ecosystems to climate change and human interventions remains difficult partly due to a lack of comprehensive understanding of SPM concentrations and fluxes across time scales from intratidal to seasonal and interannual variability. We investigate the dynamics of suspended sediment and suspended particulate matter in a hypertidal estuary with a maximum tidal range in excess of 10 m and tidal currents reaching over 1 m/s: the Dee Estuary. This estuary is located in northwest England and outflows in Liverpool Bay, itself in the eastern Irish Sea. The Dee Estuary is a funnel-shaped, coastal plain estuary, which is about 30 km long with a maximum width of 8.5 km at the mouth, and consists of mixed sediments. We focus on field observations, collected during several campaigns in the channels of the Dee Estuary from 2004 to 2009 using acoustic and optical instrumentation, which provide intratidal measurements of flow velocity and suspended sediment, and thus sediment fluxes, over approximately a month. Measurements in February-March 2008 highlight three distinct hydrodynamic regimes: a current dominant regime at neap tides (14-21 February); a combined wave-current regime at spring tides (21-29 February); and a wave dominant regime at neap tide (1-4 March). While analysis of tidal distortion and dominance predicts weak ebb dominant channels, the observations yield flood dominant sediment transport. The net sediment flux exhibits a two-layer structure - import near the bed, export near the surface - that is consistent with the residual

  3. Preoperative mapping of cortical language areas in adult brain tumour patients using PET and individual non-normalised SPM analyses

    International Nuclear Information System (INIS)

    Meyer, Philipp T.; Sturz, Laszlo; Schreckenberger, Mathias; Setani, Keyvan S.; Buell, Udalrich; Spetzger, Uwe; Meyer, Georg F.; Sabri, Osama

    2003-01-01

    In patients scheduled for the resection of perisylvian brain tumours, knowledge of the cortical topography of language functions is crucial in order to avoid neurological deficits. We investigated the applicability of statistical parametric mapping (SPM) without stereotactic normalisation for individual preoperative language function brain mapping using positron emission tomography (PET). Seven right-handed adult patients with left-sided brain tumours (six frontal and one temporal) underwent 12 oxygen-15 labelled water PET scans during overt verb generation and rest. Individual activation maps were calculated for P<0.005 and P<0.001 without anatomical normalisation and overlaid onto the individuals' magnetic resonance images for preoperative planning. Activations corresponding to Broca's and Wernicke's areas were found in five and six cases, respectively, for P<0.005 and in three and six cases, respectively, for P<0.001. One patient with a glioma located in the classical Broca's area without aphasic symptoms presented an activation of the adjacent inferior frontal cortex and of a right-sided area homologous to Broca's area. Four additional patients with left frontal tumours also presented activations of the right-sided Broca's homologue; two of these showed aphasic symptoms and two only a weak or no activation of Broca's area. Other frequently observed activations included bilaterally the superior temporal gyri, prefrontal cortices, anterior insulae, motor areas and the cerebellum. The middle and inferior temporal gyri were activated predominantly on the left. An SPM group analysis (P<0.05, corrected) in patients with left frontal tumours confirmed the activation pattern shown by the individual analyses. We conclude that SPM analyses without stereotactic normalisation offer a promising alternative for analysing individual preoperative language function brain mapping studies. The observed right frontal activations agree with proposed reorganisation processes, but

  4. Regulation of suspended particulate matter (SPM) in Indian coal-based thermal power plants

    Science.gov (United States)

    Sengupta, Ishita

    Air borne particulate matter, in major Indian cities is at least three times the standard prescribed by the WHO. Coal-based thermal power plants are the major emitters of particulate matter in India. The lack of severe penalty for non-compliance with the standards has worsened the situation and thus calls for an immediate need for investment in technologies to regulate particulate emissions. My dissertation studies the optimal investment decisions in a dynamic framework, for a random sample of forty Indian coal-based power plants to abate particulate emissions. I used Linear Programming to solve the double cost minimization problem for the optimal choices of coal, boiler and pollution-control equipment. A policy analysis is done to choose over various tax policies, which would induce the firms to adopt the energy efficient as well as cost efficient technology. The aim here is to reach the WHO standards. Using the optimal switching point model I show that in a dynamic set up, switching the boiler immediately is always the cost effective option for all the power plants even if there is no policy restriction. The switch to a baghouse depends upon the policy in place. Theoretically, even though an emission tax is considered the most efficient tax, an ash tax or a coal tax can also be considered to be a good substitute especially in countries like India where monitoring costs are very high. As SPM is a local pollutant the analysis here is mainly firm specific.

  5. Ansiedad y diagnóstico del síndrome premenstrual (SPM

    Directory of Open Access Journals (Sweden)

    CARMEN BORRÁS SANSALONI

    2001-01-01

    Full Text Available La falta de una definición clara y unánime del trastorno constituye uno de los principales problemas metodológicos en la evaluación del síndro m e premenstrual (SPM, dificultando enormemente la diferenciación entre los denominados cambios premenstruales negativos (CPM- y el verdadero síndrome premenstrual (SPM. Algunos autores, con el objeto de solucionar este problema, han propuesto una serie de criterios para el correcto diagnóstico del SPM, criterios que hacen referencia a síntomas tanto emocionales como comportamentales relacionados con la fase premenstrual del ciclo ovárico y cuya severidad interfiere significativamente en la vida cotidiana de las mujeres que los padecen No obstante, por una parte, algunos autores han señalado que dichos criterios diagnósticos se refieren a una manifestación ideal del trastorno y, por otra, numerosos estudios han demostrado que el patrón general de ansiedad constituye uno de los principales factores implicados en el padecimiento del SPM. En el presente trabajo, realizado con una muestra de 133 mujeres se analiza la posible relación entre el patrón general de ansiedad así como de las respuestas emocionales manifestadas en las diferentes fases del ciclo menstrual y los criterios diagnósticos del SPM.

  6. The effects of the internal flow structure on SPM entrapment in the Rotterdam Waterway

    NARCIS (Netherlands)

    De Nijs, M.A.J.; Winterwerp, J.C.; Pietrzak, J.D.

    2010-01-01

    Field measurements are presented, which are the first to quantify the processes influencing the entrapment of suspended particulate matter (SPM) at the limit of saltwater intrusion in the Rotterdam Waterway. The estuarine turbidity maximum (ETM) is shown to be maintained by the trapping of fluvial

  7. Efficient constraint-based Sequential Pattern Mining (SPM algorithm to understand customers’ buying behaviour from time stamp-based sequence dataset

    Directory of Open Access Journals (Sweden)

    Niti Ashish Kumar Desai

    2015-12-01

    Full Text Available Business Strategies are formulated based on an understanding of customer needs. This requires development of a strategy to understand customer behaviour and buying patterns, both current and future. This involves understanding, first how an organization currently understands customer needs and second predicting future trends to drive growth. This article focuses on purchase trend of customer, where timing of purchase is more important than association of item to be purchased, and which can be found out with Sequential Pattern Mining (SPM methods. Conventional SPM algorithms worked purely on frequency identifying patterns that were more frequent but suffering from challenges like generation of huge number of uninteresting patterns, lack of user’s interested patterns, rare item problem, etc. Article attempts a solution through development of a SPM algorithm based on various constraints like Gap, Compactness, Item, Recency, Profitability and Length along with Frequency constraint. Incorporation of six additional constraints is as well to ensure that all patterns are recently active (Recency, active for certain time span (Compactness, profitable and indicative of next timeline for purchase (Length―Item―Gap. The article also attempts to throw light on how proposed Constraint-based Prefix Span algorithm is helpful to understand buying behaviour of customer which is in formative stage.

  8. Distribution, partitioning and sources of polycyclic aromatic hydrocarbons in the water-SPM-sediment system of Lake Chaohu, China

    DEFF Research Database (Denmark)

    Qin, Ning; He, Wei; Kong, Xiang-Zhen

    2014-01-01

    The residual levels of polycyclic aromatic hydrocarbons (PAHs) in the water, suspended particular matter (SPM) and sediment from Lake Chaohu were measured with a gas chromatograph-mass spectrometer (GC-MS). The spatial-temporal distributions and the SPM-water partition of PAHs and their influenci...

  9. Assessment of SPM in perfusion brain SPECT studies. A numerical simulation study using bootstrap resampling methods.

    Science.gov (United States)

    Pareto, Deborah; Aguiar, Pablo; Pavía, Javier; Gispert, Juan Domingo; Cot, Albert; Falcón, Carles; Benabarre, Antoni; Lomeña, Francisco; Vieta, Eduard; Ros, Domènec

    2008-07-01

    Statistical parametric mapping (SPM) has become the technique of choice to statistically evaluate positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and single photon emission computed tomography (SPECT) functional brain studies. Nevertheless, only a few methodological studies have been carried out to assess the performance of SPM in SPECT. The aim of this paper was to study the performance of SPM in detecting changes in regional cerebral blood flow (rCBF) in hypo- and hyperperfused areas in brain SPECT studies. The paper seeks to determine the relationship between the group size and the rCBF changes, and the influence of the correction for degradations. The assessment was carried out using simulated brain SPECT studies. Projections were obtained with Monte Carlo techniques, and a fan-beam collimator was considered in the simulation process. Reconstruction was performed by using the ordered subsets expectation maximization (OSEM) algorithm with and without compensation for attenuation, scattering, and spatial variant collimator response. Significance probability maps were obtained with SPM2 by using a one-tailed two-sample t-test. A bootstrap resampling approach was used to determine the sample size for SPM to detect the between-group differences. Our findings show that the correction for degradations results in a diminution of the sample size, which is more significant for small regions and low-activation factors. Differences in sample size were found between hypo- and hyperperfusion. These differences were larger for small regions and low-activation factors, and when no corrections were included in the reconstruction algorithm.

  10. Brain imaging analysis can identify participants under regular mental training.

    Science.gov (United States)

    Sato, João R; Kozasa, Elisa H; Russell, Tamara A; Radvany, João; Mello, Luiz E A M; Lacerda, Shirley S; Amaro, Edson

    2012-01-01

    Multivariate pattern recognition approaches have become a prominent tool in neuroimaging data analysis. These methods enable the classification of groups of participants (e.g. controls and patients) on the basis of subtly different patterns across the whole brain. This study demonstrates that these methods can be used, in combination with automated morphometric analysis of structural MRI, to determine with great accuracy whether a single subject has been engaged in regular mental training or not. The proposed approach allowed us to identify with 94.87% accuracy (pimaging applications, in which participants could be identified based on their mental experience.

  11. Monitoring of suspended particulate matter (SPM), heavy metals and other parameters in some workplaces

    International Nuclear Information System (INIS)

    Kinyua, A.M.; Gatebe, C.K.; Mangala, M.J.; Korir, A.K.; Bartilol, S.; Maina, D.M.; Mugera, W.G.; Kamau, G.N.; Chakaya, J.M.; Karama, M.; Miungu, D.M.; Kitio, V.

    2000-01-01

    This report presents results of measurements of sound levels, chemical analysis of air particulate matter and soil samples from two factories in Nairobi. A preliminary assessment of suspended particulate matter (SPM) in a residential site and its possible impacts on acute respiratory infections (ARI) of children under five years of age is also reported. Our investigations show that for Factory A, the Soil pH measurements within the Factory were more basic (pH=8.5) than those collected near a complainant's residence (pH=7.2). The sound level measurements showed that the maximum noise level recorded was 90 dB. This was at a distance of about 0.5 m from the main exhaust vent of the Factory (20 m above ground level). There was a strong ''detergent-perfume'' odour within and outside the Factory premises especially towards the complainant's side. However, the odour fluctuated. There was also no smoke emissions noticed during the site visits when the factory was operational. For Factory B, the major source of environmental degradation was drainage and management of the factory effluents. The BOD and COD levels for effluents samples analyzed ( 3 whereas the fine particles ranged from 16.2-24.4 μm/m 3 . The prevalence of ARI cases in 1998 ranged between 29.9% in January to the highest level of 59.6% in June. The total number of children who presented themselves throughout the study period, January-December 1998, was 146. A parallel study of dust sampling was also carried out from January to December 1998 in a typical office environment. Dust levels recorded from the working office environment at the Institute of Nuclear Science was found to range from 0. 44 -1.79 μg/cm 2 /day. (author)

  12. Identifying Importance-Performance Matrix Analysis (IPMA) of ...

    African Journals Online (AJOL)

    The results of the study revealed that human capital, organizational capital, technological capital and Islamic work ethics significantly influenced business performance. Then, this study explored the use of the Importance-Performance matrix analysis to identify priority factors that can be enhanced to increase business ...

  13. Identifying Students’ Misconceptions on Basic Algorithmic Concepts Through Flowchart Analysis

    NARCIS (Netherlands)

    Rahimi, E.; Barendsen, E.; Henze, I.; Dagienė, V.; Hellas, A.

    2017-01-01

    In this paper, a flowchart-based approach to identifying secondary school students’ misconceptions (in a broad sense) on basic algorithm concepts is introduced. This approach uses student-generated flowcharts as the units of analysis and examines them against plan composition and construct-based

  14. BIOELECTRICAL IMPEDANCE VECTOR ANALYSIS IDENTIFIES SARCOPENIA IN NURSING HOME RESIDENTS

    Science.gov (United States)

    Loss of muscle mass and water shifts between body compartments are contributing factors to frailty in the elderly. The body composition changes are especially pronounced in institutionalized elderly. We investigated the ability of single-frequency bioelectrical impedance analysis (BIA) to identify b...

  15. Identifying subgroups of patients using latent class analysis

    DEFF Research Database (Denmark)

    Nielsen, Anne Mølgaard; Kent, Peter; Hestbæk, Lise

    2017-01-01

    BACKGROUND: Heterogeneity in patients with low back pain (LBP) is well recognised and different approaches to subgrouping have been proposed. Latent Class Analysis (LCA) is a statistical technique that is increasingly being used to identify subgroups based on patient characteristics. However...

  16. Identifying clinical course patterns in SMS data using cluster analysis.

    Science.gov (United States)

    Kent, Peter; Kongsted, Alice

    2012-07-02

    Recently, there has been interest in using the short message service (SMS or text messaging), to gather frequent information on the clinical course of individual patients. One possible role for identifying clinical course patterns is to assist in exploring clinically important subgroups in the outcomes of research studies. Two previous studies have investigated detailed clinical course patterns in SMS data obtained from people seeking care for low back pain. One used a visual analysis approach and the other performed a cluster analysis of SMS data that had first been transformed by spline analysis. However, cluster analysis of SMS data in its original untransformed form may be simpler and offer other advantages. Therefore, the aim of this study was to determine whether cluster analysis could be used for identifying clinical course patterns distinct from the pattern of the whole group, by including all SMS time points in their original form. It was a 'proof of concept' study to explore the potential, clinical relevance, strengths and weakness of such an approach. This was a secondary analysis of longitudinal SMS data collected in two randomised controlled trials conducted simultaneously from a single clinical population (n = 322). Fortnightly SMS data collected over a year on 'days of problematic low back pain' and on 'days of sick leave' were analysed using Two-Step (probabilistic) Cluster Analysis. Clinical course patterns were identified that were clinically interpretable and different from those of the whole group. Similar patterns were obtained when the number of SMS time points was reduced to monthly. The advantages and disadvantages of this method were contrasted to that of first transforming SMS data by spline analysis. This study showed that clinical course patterns can be identified by cluster analysis using all SMS time points as cluster variables. This method is simple, intuitive and does not require a high level of statistical skill. However, there

  17. Evaluation of the new radiation belt AE9/AP9/SPM model for a cislunar mission

    Science.gov (United States)

    Badavi, Francis F.; Walker, Steven A.; Santos Koos, Lindsey M.

    2014-09-01

    this time. From a mission planning point of view, this date is ideal as the predictable GCR exposure will be at a maximum, while the sporadic SEP will be at a minimum. In addition, it is anticipated that by 2020 a vehicle capable of launching a crew of four will be operationally ready. During the LEO-GEO transit, the crew and cargo vehicles will encounter exposure from trapped particles and attenuated GCR, followed by free space exposure due to GCR and SEP during solar active times. Within the trapped field, a challenge arises from properly calculating the amount of exposure acquired. Within this field, in the absence of SEP (i.e. solar quiet times), the vehicles will have to transit through an inner proton belt, an inner and outer electron belts, and an attenuated GCR field. There exist a number of models to define the intensities of the trapped particles during the quiet and active SEP. Among the more established trapped models are the historic and popular electron/proton AE8/AP8 model dating back to the 1980s, the historic and less popular electron/proton CRRES model dating back to 1990s, and the recently released electron/proton/space plasma AE9/AP9/SPM model. The AE9/AP9/SPM model is a major improvement over the older AE8/AP8 and CRRES models. This model is derived from numerous measurements acquired over four solar cycles dating back to the 1970s, roughly representing 40 years of data collection. In contrast, the older AE8/AP8 and CRRES models were limited to only a few months of measurements taken during the prior solar minima and maxima. In this work, within the trapped field, along the design trajectory of the crew vehicle, the AE9/AP9/SPM model is evaluated against the older AE8/AP8 model during solar quiet times. The analysis is then extended to the GCR dominated en-route, cislunar L2 space and return trajectories in order to provide cumulative exposure estimates to the crew vehicle for the duration of the entire mission.

  18. Practical identifiability analysis of a minimal cardiovascular system model.

    Science.gov (United States)

    Pironet, Antoine; Docherty, Paul D; Dauby, Pierre C; Chase, J Geoffrey; Desaive, Thomas

    2017-01-17

    Parameters of mathematical models of the cardiovascular system can be used to monitor cardiovascular state, such as total stressed blood volume status, vessel elastance and resistance. To do so, the model parameters have to be estimated from data collected at the patient's bedside. This work considers a seven-parameter model of the cardiovascular system and investigates whether these parameters can be uniquely determined using indices derived from measurements of arterial and venous pressures, and stroke volume. An error vector defined the residuals between the simulated and reference values of the seven clinically available haemodynamic indices. The sensitivity of this error vector to each model parameter was analysed, as well as the collinearity between parameters. To assess practical identifiability of the model parameters, profile-likelihood curves were constructed for each parameter. Four of the seven model parameters were found to be practically identifiable from the selected data. The remaining three parameters were practically non-identifiable. Among these non-identifiable parameters, one could be decreased as much as possible. The other two non-identifiable parameters were inversely correlated, which prevented their precise estimation. This work presented the practical identifiability analysis of a seven-parameter cardiovascular system model, from limited clinical data. The analysis showed that three of the seven parameters were practically non-identifiable, thus limiting the use of the model as a monitoring tool. Slight changes in the time-varying function modeling cardiac contraction and use of larger values for the reference range of venous pressure made the model fully practically identifiable. Copyright © 2017. Published by Elsevier B.V.

  19. Latent cluster analysis of ALS phenotypes identifies prognostically differing groups.

    Directory of Open Access Journals (Sweden)

    Jeban Ganesalingam

    2009-09-01

    Full Text Available Amyotrophic lateral sclerosis (ALS is a degenerative disease predominantly affecting motor neurons and manifesting as several different phenotypes. Whether these phenotypes correspond to different underlying disease processes is unknown. We used latent cluster analysis to identify groupings of clinical variables in an objective and unbiased way to improve phenotyping for clinical and research purposes.Latent class cluster analysis was applied to a large database consisting of 1467 records of people with ALS, using discrete variables which can be readily determined at the first clinic appointment. The model was tested for clinical relevance by survival analysis of the phenotypic groupings using the Kaplan-Meier method.The best model generated five distinct phenotypic classes that strongly predicted survival (p<0.0001. Eight variables were used for the latent class analysis, but a good estimate of the classification could be obtained using just two variables: site of first symptoms (bulbar or limb and time from symptom onset to diagnosis (p<0.00001.The five phenotypic classes identified using latent cluster analysis can predict prognosis. They could be used to stratify patients recruited into clinical trials and generating more homogeneous disease groups for genetic, proteomic and risk factor research.

  20. [Elaboration of the SPM template for the standardization of SPECT images with 123I-Ioflupane].

    Science.gov (United States)

    García-Gómez, F J; García-Solís, D; Luis-Simón, F J; Marín-Oyaga, V A; Carrillo, F; Mir, P; Vázquez-Albertino, R J

    2013-01-01

    Statistical parametric mapping (SPM) is a widely used produced for normalization of functional images. This study has aimed to develop a normalization template of (123)I-Ioflupane SPECT-imaging DaTSCAN(®), GE Healthcare), not available in SPM5, and to validate it compared to other quantification methods. In order to write the template we retrospectively selected 26 subjects who had no evidence of nigrostriatal degeneration and whose age distribution was similar to that of the patients in the usual practice of our Department: 2 subjects (7.6%) were 65 years (57.7%). All the studies were normalized with the T1-template available in SPM5 and an average image of the value was obtained for each voxel. For validation we analyzed 60 patients: 30 with idiopathic Parkinson's disease patients (iPD) with right involvement (66.83±12.20 years) and 30 with essential tremor patients (ET) (67.27±8.33 years). Specific uptake rates (SUR) of different striatal regions were compared after image normalization with our template and the application of a semiautomated VOIs-map created with Analyze v9.0 ((©)BIR, Mayo Clinic), against two quantification methods: a) manual adjustment of a ROIs-map drawn in Analyze, and b) semi-automated method (HERMES-BRASS) with normalization and implementation of VOIs-map. No statistically significant differences in the iPD/ET discriminatory capacity between the three methods analyzed were observed (p0,871, p<0,001). This difference was greater in patients with PD. Our study demonstrates the efficacy of our SPM «template» for (123)I-Ioflupane SPECT-imaging, obtained from normalization with «T1-template». Copyright © 2012 Elsevier España, S.L. and SEMNIM. All rights reserved.

  1. Introduction of a high throughput SPM for defect inspection and process control

    Science.gov (United States)

    Sadeghian, H.; Koster, N. B.; van den Dool, T. C.

    2013-04-01

    The main driver for Semiconductor and Bio-MEMS industries is decreasing the feature size, moving from the current state-of-the-art at 22 nm towards 10 nm node. Consequently smaller defects and particles become problematic due to size and number, thus inspecting and characterizing them are very challenging. Existing industrial metrology and inspection methods cannot fulfil the requirements for these smaller features. Scanning probe Microscopy (SPM) has the distinct advantage of being able to discern the atomic structure of the substrate. It can image the 3D topography, but also a variety of material, mechanical and chemical properties. Therefore SPM has been suggested as one of the technologies that can fulfil the future requirements in terms of resolution and accuracy, while being capable of resolving 3D futures. However, the throughput of the current state-of-the-art SPMs are extremely low, as compared to the high-volume manufacturing requirements. This paper presents the development of an architecture[1] for a fully automated high throughput SPM, which can meet the requirements of future process metrology and inspection for 450 mm wafers. The targeted specifications of the concept are 1) inspecting more than 20 sites per wafer, 2) each site with dimension of about 10 × 10 μm2 (scalable to 100 × 100 μm2) and 3) with a throughput of more than 7 wafers per hour, or 70 wafers per hour with a coarse/fine scanning approach. The progress of the high throughput SPM development is discussed and the baseline design of the critical sub-modules and the research issues are presented.

  2. Identifying Organizational Inefficiencies with Pictorial Process Analysis (PPA

    Directory of Open Access Journals (Sweden)

    David John Patrishkoff

    2013-11-01

    Full Text Available Pictorial Process Analysis (PPA was created by the author in 2004. PPA is a unique methodology which offers ten layers of additional analysis when compared to standard process mapping techniques.  The goal of PPA is to identify and eliminate waste, inefficiencies and risk in manufacturing or transactional business processes at 5 levels in an organization. The highest level being assessed is the process management, followed by the process work environment, detailed work habits, process performance metrics and general attitudes towards the process. This detailed process assessment and analysis is carried out during process improvement brainstorming efforts and Kaizen events. PPA creates a detailed visual efficiency rating for each step of the process under review.  A selection of 54 pictorial Inefficiency Icons (cards are available for use to highlight major inefficiencies and risks that are present in the business process under review. These inefficiency icons were identified during the author's independent research on the topic of why things go wrong in business. This paper will highlight how PPA was developed and show the steps required to conduct Pictorial Process Analysis on a sample manufacturing process. The author has successfully used PPA to dramatically improve business processes in over 55 different industries since 2004.  

  3. Dynamic Allocation of SPM Based on Time-Slotted Cache Conflict Graph for System Optimization

    Science.gov (United States)

    Wu, Jianping; Ling, Ming; Zhang, Yang; Mei, Chen; Wang, Huan

    This paper proposes a novel dynamic Scratch-pad Memory allocation strategy to optimize the energy consumption of the memory sub-system. Firstly, the whole program execution process is sliced into several time slots according to the temporal dimension; thereafter, a Time-Slotted Cache Conflict Graph (TSCCG) is introduced to model the behavior of Data Cache (D-Cache) conflicts within each time slot. Then, Integer Nonlinear Programming (INP) is implemented, which can avoid time-consuming linearization process, to select the most profitable data pages. Virtual Memory System (VMS) is adopted to remap those data pages, which will cause severe Cache conflicts within a time slot, to SPM. In order to minimize the swapping overhead of dynamic SPM allocation, a novel SPM controller with a tightly coupled DMA is introduced to issue the swapping operations without CPU's intervention. Last but not the least, this paper discusses the fluctuation of system energy profit based on different MMU page size as well as the Time Slot duration quantitatively. According to our design space exploration, the proposed method can optimize all of the data segments, including global data, heap and stack data in general, and reduce the total energy consumption by 27.28% on average, up to 55.22% with a marginal performance promotion. And comparing to the conventional static CCG (Cache Conflicts Graph), our approach can obtain 24.7% energy profit on average, up to 30.5% with a sight boost in performance.

  4. Rice Transcriptome Analysis to Identify Possible Herbicide Quinclorac Detoxification Genes

    Directory of Open Access Journals (Sweden)

    Wenying eXu

    2015-09-01

    Full Text Available Quinclorac is a highly selective auxin-type herbicide, and is widely used in the effective control of barnyard grass in paddy rice fields, improving the world’s rice yield. The herbicide mode of action of quinclorac has been proposed and hormone interactions affect quinclorac signaling. Because of widespread use, quinclorac may be transported outside rice fields with the drainage waters, leading to soil and water pollution and environmental health problems.In this study, we used 57K Affymetrix rice whole-genome array to identify quinclorac signaling response genes to study the molecular mechanisms of action and detoxification of quinclorac in rice plants. Overall, 637 probe sets were identified with differential expression levels under either 6 or 24 h of quinclorac treatment. Auxin-related genes such as GH3 and OsIAAs responded to quinclorac treatment. Gene Ontology analysis showed that genes of detoxification-related family genes were significantly enriched, including cytochrome P450, GST, UGT, and ABC and drug transporter genes. Moreover, real-time RT-PCR analysis showed that top candidate P450 families such as CYP81, CYP709C and CYP72A genes were universally induced by different herbicides. Some Arabidopsis genes for the same P450 family were up-regulated under quinclorac treatment.We conduct rice whole-genome GeneChip analysis and the first global identification of quinclorac response genes. This work may provide potential markers for detoxification of quinclorac and biomonitors of environmental chemical pollution.

  5. Proteogenomic Analysis Identifies a Novel Human SHANK3 Isoform

    Directory of Open Access Journals (Sweden)

    Fahad Benthani

    2015-05-01

    Full Text Available Mutations of the SHANK3 gene have been associated with autism spectrum disorder. Individuals harboring different SHANK3 mutations display considerable heterogeneity in their cognitive impairment, likely due to the high SHANK3 transcriptional diversity. In this study, we report a novel interaction between the Mutated in colorectal cancer (MCC protein and a newly identified SHANK3 protein isoform in human colon cancer cells and mouse brain tissue. Hence, our proteogenomic analysis identifies a new human long isoform of the key synaptic protein SHANK3 that was not predicted by the human reference genome. Taken together, our findings describe a potential new role for MCC in neurons, a new human SHANK3 long isoform and, importantly, highlight the use of proteomic data towards the re-annotation of GC-rich genomic regions.

  6. Parameter trajectory analysis to identify treatment effects of pharmacological interventions.

    Directory of Open Access Journals (Sweden)

    Christian A Tiemann

    Full Text Available The field of medical systems biology aims to advance understanding of molecular mechanisms that drive disease progression and to translate this knowledge into therapies to effectively treat diseases. A challenging task is the investigation of long-term effects of a (pharmacological treatment, to establish its applicability and to identify potential side effects. We present a new modeling approach, called Analysis of Dynamic Adaptations in Parameter Trajectories (ADAPT, to analyze the long-term effects of a pharmacological intervention. A concept of time-dependent evolution of model parameters is introduced to study the dynamics of molecular adaptations. The progression of these adaptations is predicted by identifying necessary dynamic changes in the model parameters to describe the transition between experimental data obtained during different stages of the treatment. The trajectories provide insight in the affected underlying biological systems and identify the molecular events that should be studied in more detail to unravel the mechanistic basis of treatment outcome. Modulating effects caused by interactions with the proteome and transcriptome levels, which are often less well understood, can be captured by the time-dependent descriptions of the parameters. ADAPT was employed to identify metabolic adaptations induced upon pharmacological activation of the liver X receptor (LXR, a potential drug target to treat or prevent atherosclerosis. The trajectories were investigated to study the cascade of adaptations. This provided a counter-intuitive insight concerning the function of scavenger receptor class B1 (SR-B1, a receptor that facilitates the hepatic uptake of cholesterol. Although activation of LXR promotes cholesterol efflux and -excretion, our computational analysis showed that the hepatic capacity to clear cholesterol was reduced upon prolonged treatment. This prediction was confirmed experimentally by immunoblotting measurements of SR-B1

  7. Lidar point density analysis: implications for identifying water bodies

    Science.gov (United States)

    Worstell, Bruce B.; Poppenga, Sandra K.; Evans, Gayla A.; Prince, Sandra

    2014-01-01

    Most airborne topographic light detection and ranging (lidar) systems operate within the near-infrared spectrum. Laser pulses from these systems frequently are absorbed by water and therefore do not generate reflected returns on water bodies in the resulting void regions within the lidar point cloud. Thus, an analysis of lidar voids has implications for identifying water bodies. Data analysis techniques to detect reduced lidar return densities were evaluated for test sites in Blackhawk County, Iowa, and Beltrami County, Minnesota, to delineate contiguous areas that have few or no lidar returns. Results from this study indicated a 5-meter radius moving window with fewer than 23 returns (28 percent of the moving window) was sufficient for delineating void regions. Techniques to provide elevation values for void regions to flatten water features and to force channel flow in the downstream direction also are presented.

  8. Identifying radiotherapy target volumes in brain cancer by image analysis.

    Science.gov (United States)

    Cheng, Kun; Montgomery, Dean; Feng, Yang; Steel, Robin; Liao, Hanqing; McLaren, Duncan B; Erridge, Sara C; McLaughlin, Stephen; Nailon, William H

    2015-10-01

    To establish the optimal radiotherapy fields for treating brain cancer patients, the tumour volume is often outlined on magnetic resonance (MR) images, where the tumour is clearly visible, and mapped onto computerised tomography images used for radiotherapy planning. This process requires considerable clinical experience and is time consuming, which will continue to increase as more complex image sequences are used in this process. Here, the potential of image analysis techniques for automatically identifying the radiation target volume on MR images, and thereby assisting clinicians with this difficult task, was investigated. A gradient-based level set approach was applied on the MR images of five patients with grades II, III and IV malignant cerebral glioma. The relationship between the target volumes produced by image analysis and those produced by a radiation oncologist was also investigated. The contours produced by image analysis were compared with the contours produced by an oncologist and used for treatment. In 93% of cases, the Dice similarity coefficient was found to be between 60 and 80%. This feasibility study demonstrates that image analysis has the potential for automatic outlining in the management of brain cancer patients, however, more testing and validation on a much larger patient cohort is required.

  9. Using lexical analysis to identify emotional distress in psychometric schizotypy.

    Science.gov (United States)

    Abplanalp, Samuel J; Buck, Benjamin; Gonzenbach, Virgilio; Janela, Carlos; Lysaker, Paul H; Minor, Kyle S

    2017-09-01

    Through the use of lexical analysis software, researchers have demonstrated a greater frequency of negative affect word use in those with schizophrenia and schizotypy compared to the general population. In addition, those with schizotypy endorse greater emotional distress than healthy controls. In this study, our aim was to expand on previous findings in schizotypy to determine whether negative affect word use could be linked to emotional distress. Schizotypy (n=33) and non-schizotypy groups (n=33) completed an open-ended, semi-structured interview and negative affect word use was analyzed using a validated lexical analysis instrument. Emotional distress was assessed using subjective questionnaires of depression and psychological quality of life (QOL). When groups were compared, those with schizotypy used significantly more negative affect words; endorsed greater depression; and reported lower QOL. Within schizotypy, a trend level association between depression and negative affect word use was observed; QOL and negative affect word use showed a significant inverse association. Our findings offer preliminary evidence of the potential effectiveness of lexical analysis as an objective, behavior-based method for identifying emotional distress throughout the schizophrenia-spectrum. Utilizing lexical analysis in schizotypy offers promise for providing researchers with an assessment capable of objectively detecting emotional distress. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  10. Use of discriminant analysis to identify propensity for purchasing properties

    Directory of Open Access Journals (Sweden)

    Ricardo Floriani

    2015-03-01

    Full Text Available Properties usually represent a milestone for people and families due to the high added-value when compared with family income. The objective of this study is the proposition of a discrimination model, by a discriminant analysis of people with characteristics (according to independent variables classified as potential buyers of properties, as well as to identify the interest in the use of such property, if it will be assigned to housing or leisure activities such as a cottage or beach house, and/or for investment. Thus, the following research question is proposed: What are the characteristics that better describe the profile of people which intend to acquire properties? The study justifies itself by its economic relevance in the real estate industry, as well as to the players of the real estate Market that may develop products based on the profile of potential customers. As a statistical technique, discriminant analysis was applied to the data gathered by questionnaire, which was sent via e-mail. Three hundred and thirty four responses were gathered. Based on this study, it was observed that it is possible to identify the intention for acquired properties, as well the purpose for acquiring it, for housing or investments.

  11. Cluster analysis of clinical data identifies fibromyalgia subgroups.

    Directory of Open Access Journals (Sweden)

    Elisa Docampo

    Full Text Available INTRODUCTION: Fibromyalgia (FM is mainly characterized by widespread pain and multiple accompanying symptoms, which hinder FM assessment and management. In order to reduce FM heterogeneity we classified clinical data into simplified dimensions that were used to define FM subgroups. MATERIAL AND METHODS: 48 variables were evaluated in 1,446 Spanish FM cases fulfilling 1990 ACR FM criteria. A partitioning analysis was performed to find groups of variables similar to each other. Similarities between variables were identified and the variables were grouped into dimensions. This was performed in a subset of 559 patients, and cross-validated in the remaining 887 patients. For each sample and dimension, a composite index was obtained based on the weights of the variables included in the dimension. Finally, a clustering procedure was applied to the indexes, resulting in FM subgroups. RESULTS: VARIABLES CLUSTERED INTO THREE INDEPENDENT DIMENSIONS: "symptomatology", "comorbidities" and "clinical scales". Only the two first dimensions were considered for the construction of FM subgroups. Resulting scores classified FM samples into three subgroups: low symptomatology and comorbidities (Cluster 1, high symptomatology and comorbidities (Cluster 2, and high symptomatology but low comorbidities (Cluster 3, showing differences in measures of disease severity. CONCLUSIONS: We have identified three subgroups of FM samples in a large cohort of FM by clustering clinical data. Our analysis stresses the importance of family and personal history of FM comorbidities. Also, the resulting patient clusters could indicate different forms of the disease, relevant to future research, and might have an impact on clinical assessment.

  12. Proteomic Analysis of the Soybean Symbiosome Identifies New Symbiotic Proteins*

    Science.gov (United States)

    Clarke, Victoria C.; Loughlin, Patrick C.; Gavrin, Aleksandr; Chen, Chi; Brear, Ella M.; Day, David A.; Smith, Penelope M.C.

    2015-01-01

    Legumes form a symbiosis with rhizobia in which the plant provides an energy source to the rhizobia bacteria that it uses to fix atmospheric nitrogen. This nitrogen is provided to the legume plant, allowing it to grow without the addition of nitrogen fertilizer. As part of the symbiosis, the bacteria in the infected cells of a new root organ, the nodule, are surrounded by a plant-derived membrane, the symbiosome membrane, which becomes the interface between the symbionts. Fractions containing the symbiosome membrane (SM) and material from the lumen of the symbiosome (peribacteroid space or PBS) were isolated from soybean root nodules and analyzed using nongel proteomic techniques. Bicarbonate stripping and chloroform-methanol extraction of isolated SM were used to reduce complexity of the samples and enrich for hydrophobic integral membrane proteins. One hundred and ninety-seven proteins were identified as components of the SM, with an additional fifteen proteins identified from peripheral membrane and PBS protein fractions. Proteins involved in a range of cellular processes such as metabolism, protein folding and degradation, membrane trafficking, and solute transport were identified. These included a number of proteins previously localized to the SM, such as aquaglyceroporin nodulin 26, sulfate transporters, remorin, and Rab7 homologs. Among the proteome were a number of putative transporters for compounds such as sulfate, calcium, hydrogen ions, peptide/dicarboxylate, and nitrate, as well as transporters for which the substrate is not easy to predict. Analysis of the promoter activity for six genes encoding putative SM proteins showed nodule specific expression, with five showing expression only in infected cells. Localization of two proteins was confirmed using GFP-fusion experiments. The data have been deposited to the ProteomeXchange with identifier PXD001132. This proteome will provide a rich resource for the study of the legume-rhizobium symbiosis. PMID

  13. Spatial analysis to identify disparities in Philippine public school facilities

    Directory of Open Access Journals (Sweden)

    Ligaya Leah Figueroa

    2016-01-01

    Full Text Available This paper addresses the issues that affect school building conditions as a case study of the Philippines. Geographic information systems were utilized to investigate the allocation of public school resources and the extent of disparity in education facilities among 75 Philippine provinces. Four clusters of the provinces were identified by applying spatial statistics and regionalization techniques to the public school data. Overall, the building conditions are of high quality in the northern provinces. The greater region of the capital is overcrowded but well maintained. The eastern seaboard region and the southern provinces have poor conditions due to frequent natural calamities and the prolonged civil unrest, respectively. Since the spatial analysis result shows that the school building requirements are largely unmet, some recommendations are proposed so that they can be implemented by the government in order to improve the school facilities and mitigate the existing disparities among the four clusters of the Philippines.

  14. Cluster Analysis of Clinical Data Identifies Fibromyalgia Subgroups

    Science.gov (United States)

    Docampo, Elisa; Collado, Antonio; Escaramís, Geòrgia; Carbonell, Jordi; Rivera, Javier; Vidal, Javier; Alegre, José

    2013-01-01

    Introduction Fibromyalgia (FM) is mainly characterized by widespread pain and multiple accompanying symptoms, which hinder FM assessment and management. In order to reduce FM heterogeneity we classified clinical data into simplified dimensions that were used to define FM subgroups. Material and Methods 48 variables were evaluated in 1,446 Spanish FM cases fulfilling 1990 ACR FM criteria. A partitioning analysis was performed to find groups of variables similar to each other. Similarities between variables were identified and the variables were grouped into dimensions. This was performed in a subset of 559 patients, and cross-validated in the remaining 887 patients. For each sample and dimension, a composite index was obtained based on the weights of the variables included in the dimension. Finally, a clustering procedure was applied to the indexes, resulting in FM subgroups. Results Variables clustered into three independent dimensions: “symptomatology”, “comorbidities” and “clinical scales”. Only the two first dimensions were considered for the construction of FM subgroups. Resulting scores classified FM samples into three subgroups: low symptomatology and comorbidities (Cluster 1), high symptomatology and comorbidities (Cluster 2), and high symptomatology but low comorbidities (Cluster 3), showing differences in measures of disease severity. Conclusions We have identified three subgroups of FM samples in a large cohort of FM by clustering clinical data. Our analysis stresses the importance of family and personal history of FM comorbidities. Also, the resulting patient clusters could indicate different forms of the disease, relevant to future research, and might have an impact on clinical assessment. PMID:24098674

  15. Automated network analysis identifies core pathways in glioblastoma.

    Directory of Open Access Journals (Sweden)

    Ethan Cerami

    2010-02-01

    Full Text Available Glioblastoma multiforme (GBM is the most common and aggressive type of brain tumor in humans and the first cancer with comprehensive genomic profiles mapped by The Cancer Genome Atlas (TCGA project. A central challenge in large-scale genome projects, such as the TCGA GBM project, is the ability to distinguish cancer-causing "driver" mutations from passively selected "passenger" mutations.In contrast to a purely frequency based approach to identifying driver mutations in cancer, we propose an automated network-based approach for identifying candidate oncogenic processes and driver genes. The approach is based on the hypothesis that cellular networks contain functional modules, and that tumors target specific modules critical to their growth. Key elements in the approach include combined analysis of sequence mutations and DNA copy number alterations; use of a unified molecular interaction network consisting of both protein-protein interactions and signaling pathways; and identification and statistical assessment of network modules, i.e. cohesive groups of genes of interest with a higher density of interactions within groups than between groups.We confirm and extend the observation that GBM alterations tend to occur within specific functional modules, in spite of considerable patient-to-patient variation, and that two of the largest modules involve signaling via p53, Rb, PI3K and receptor protein kinases. We also identify new candidate drivers in GBM, including AGAP2/CENTG1, a putative oncogene and an activator of the PI3K pathway; and, three additional significantly altered modules, including one involved in microtubule organization. To facilitate the application of our network-based approach to additional cancer types, we make the method freely available as part of a software tool called NetBox.

  16. Social Network Analysis Identifies Key Participants in Conservation Development.

    Science.gov (United States)

    Farr, Cooper M; Reed, Sarah E; Pejchar, Liba

    2018-03-03

    Understanding patterns of participation in private lands conservation, which is often implemented voluntarily by individual citizens and private organizations, could improve its effectiveness at combating biodiversity loss. We used social network analysis (SNA) to examine participation in conservation development (CD), a private land conservation strategy that clusters houses in a small portion of a property while preserving the remaining land as protected open space. Using data from public records for six counties in Colorado, USA, we compared CD participation patterns among counties and identified actors that most often work with others to implement CDs. We found that social network characteristics differed among counties. The network density, or proportion of connections in the network, varied from fewer than 2 to nearly 15%, and was higher in counties with smaller populations and fewer CDs. Centralization, or the degree to which connections are held disproportionately by a few key actors, was not correlated strongly with any county characteristics. Network characteristics were not correlated with the prevalence of wildlife-friendly design features in CDs. The most highly connected actors were biological and geological consultants, surveyors, and engineers. Our work demonstrates a new application of SNA to land-use planning, in which CD network patterns are examined and key actors are identified. For better conservation outcomes of CD, we recommend using network patterns to guide strategies for outreach and information dissemination, and engaging with highly connected actor types to encourage widespread adoption of best practices for CD design and stewardship.

  17. Network Analysis Identifies Disease-Specific Pathways for Parkinson's Disease.

    Science.gov (United States)

    Monti, Chiara; Colugnat, Ilaria; Lopiano, Leonardo; Chiò, Adriano; Alberio, Tiziana

    2018-01-01

    Neurodegenerative diseases are characterized by the progressive loss of specific neurons in selected regions of the central nervous system. The main clinical manifestation (movement disorders, cognitive impairment, and/or psychiatric disturbances) depends on the neuron population being primarily affected. Parkinson's disease is a common movement disorder, whose etiology remains mostly unknown. Progressive loss of dopaminergic neurons in the substantia nigra causes an impairment of the motor control. Some of the pathogenetic mechanisms causing the progressive deterioration of these neurons are not specific for Parkinson's disease but are shared by other neurodegenerative diseases, like Alzheimer's disease and amyotrophic lateral sclerosis. Here, we performed a meta-analysis of the literature of all the quantitative proteomic investigations of neuronal alterations in different models of Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis to distinguish between general and Parkinson's disease-specific pattern of neurodegeneration. Then, we merged proteomics data with genetics information from the DisGeNET database. The comparison of gene and protein information allowed us to identify 25 proteins involved uniquely in Parkinson's disease and we verified the alteration of one of them, i.e., transaldolase 1 (TALDO1), in the substantia nigra of 5 patients. By using open-source bioinformatics tools, we identified the biological processes specifically affected in Parkinson's disease, i.e., proteolysis, mitochondrion organization, and mitophagy. Eventually, we highlighted four cellular component complexes mostly involved in the pathogenesis: the proteasome complex, the protein phosphatase 2A, the chaperonins CCT complex, and the complex III of the respiratory chain.

  18. LapOntoSPM: an ontology for laparoscopic surgeries and its application to surgical phase recognition.

    Science.gov (United States)

    Katić, Darko; Julliard, Chantal; Wekerle, Anna-Laura; Kenngott, Hannes; Müller-Stich, Beat Peter; Dillmann, Rüdiger; Speidel, Stefanie; Jannin, Pierre; Gibaud, Bernard

    2015-09-01

    The rise of intraoperative information threatens to outpace our abilities to process it. Context-aware systems, filtering information to automatically adapt to the current needs of the surgeon, are necessary to fully profit from computerized surgery. To attain context awareness, representation of medical knowledge is crucial. However, most existing systems do not represent knowledge in a reusable way, hindering also reuse of data. Our purpose is therefore to make our computational models of medical knowledge sharable, extensible and interoperational with established knowledge representations in the form of the LapOntoSPM ontology. To show its usefulness, we apply it to situation interpretation, i.e., the recognition of surgical phases based on surgical activities. Considering best practices in ontology engineering and building on our ontology for laparoscopy, we formalized the workflow of laparoscopic adrenalectomies, cholecystectomies and pancreatic resections in the framework of OntoSPM, a new standard for surgical process models. Furthermore, we provide a rule-based situation interpretation algorithm based on SQWRL to recognize surgical phases using the ontology. The system was evaluated on ground-truth data from 19 manually annotated surgeries. The aim was to show that the phase recognition capabilities are equal to a specialized solution. The recognition rates of the new system were equal to the specialized one. However, the time needed to interpret a situation rose from 0.5 to 1.8 s on average which is still viable for practical application. We successfully integrated medical knowledge for laparoscopic surgeries into OntoSPM, facilitating knowledge and data sharing. This is especially important for reproducibility of results and unbiased comparison of recognition algorithms. The associated recognition algorithm was adapted to the new representation without any loss of classification power. The work is an important step to standardized knowledge and data

  19. Health risks of NO 2, SPM and SO 2 in Delhi (India)

    Science.gov (United States)

    Pandey, Jai Shanker; Kumar, Rakesh; Devotta, Sukumar

    There is increasingly growing evidence linking urban air pollution to acute and chronic illnesses amongst all age groups. Therefore, monitoring of ambient concentrations of various air pollutants as well as quantification of the dose inhaled becomes quite important, specially in view of the fact that in many countries, policy decisions for reducing pollutant concentrations are mainly taken on the basis of their health impacts. The dose when gets combined with the likely responses, indicates the ultimate health risk (HR). Thus, as an extension of our earlier studies, HR has been estimated for three pollutants, namely, suspended particulate matter (SPM), nitrogen dioxide (NO 2) and sulfur dioxide (SO 2) for Delhi City in India. For estimation and analyses, three zones have been considered, namely, residential, industrial and commercial. The total population has been divided into three age classes (infants, children and adults) with different body weights and breathing rates. The exercise takes into account age-specific breathing rates, body weights for different age categories and occupancy factors for different zones. Results indicate that health risks due to air pollution in Delhi are highest for children. For all age categories, health risks due to SO 2 (HR_SO 2) are the lowest. Hence, HR_SO 2 has been taken as the reference with respect to which HR values due to SPM and NO 2 have been compared. Taking into account all the age categories and their occupancy in different zones, average HR values for NO 2 and SPM turn out to be respectively 22.11 and 16.13 times more than that for SO 2. The present study can be useful in generating public awareness as well as in averting and mitigating the health risks.

  20. Performance Analysis: Work Control Events Identified January - August 2010

    Energy Technology Data Exchange (ETDEWEB)

    De Grange, C E; Freeman, J W; Kerr, C E; Holman, G; Marsh, K; Beach, R

    2011-01-14

    This performance analysis evaluated 24 events that occurred at LLNL from January through August 2010. The analysis identified areas of potential work control process and/or implementation weaknesses and several common underlying causes. Human performance improvement and safety culture factors were part of the causal analysis of each event and were analyzed. The collective significance of all events in 2010, as measured by the occurrence reporting significance category and by the proportion of events that have been reported to the DOE ORPS under the ''management concerns'' reporting criteria, does not appear to have increased in 2010. The frequency of reporting in each of the significance categories has not changed in 2010 compared to the previous four years. There is no change indicating a trend in the significance category and there has been no increase in the proportion of occurrences reported in the higher significance category. Also, the frequency of events, 42 events reported through August 2010, is not greater than in previous years and is below the average of 63 occurrences per year at LLNL since 2006. Over the previous four years, an average of 43% of the LLNL's reported occurrences have been reported as either ''management concerns'' or ''near misses.'' In 2010, 29% of the occurrences have been reported as ''management concerns'' or ''near misses.'' This rate indicates that LLNL is now reporting fewer ''management concern'' and ''near miss'' occurrences compared to the previous four years. From 2008 to the present, LLNL senior management has undertaken a series of initiatives to strengthen the work planning and control system with the primary objective to improve worker safety. In 2008, the LLNL Deputy Director established the Work Control Integrated Project Team to develop the core requirements and graded

  1. Behavioral metabolomics analysis identifies novel neurochemical signatures in methamphetamine sensitization

    Science.gov (United States)

    Adkins, Daniel E.; McClay, Joseph L.; Vunck, Sarah A.; Batman, Angela M.; Vann, Robert E.; Clark, Shaunna L.; Souza, Renan P.; Crowley, James J.; Sullivan, Patrick F.; van den Oord, Edwin J.C.G.; Beardsley, Patrick M.

    2014-01-01

    Behavioral sensitization has been widely studied in animal models and is theorized to reflect neural modifications associated with human psychostimulant addiction. While the mesolimbic dopaminergic pathway is known to play a role, the neurochemical mechanisms underlying behavioral sensitization remain incompletely understood. In the present study, we conducted the first metabolomics analysis to globally characterize neurochemical differences associated with behavioral sensitization. Methamphetamine-induced sensitization measures were generated by statistically modeling longitudinal activity data for eight inbred strains of mice. Subsequent to behavioral testing, nontargeted liquid and gas chromatography-mass spectrometry profiling was performed on 48 brain samples, yielding 301 metabolite levels per sample after quality control. Association testing between metabolite levels and three primary dimensions of behavioral sensitization (total distance, stereotypy and margin time) showed four robust, significant associations at a stringent metabolome-wide significance threshold (false discovery rate < 0.05). Results implicated homocarnosine, a dipeptide of GABA and histidine, in total distance sensitization, GABA metabolite 4-guanidinobutanoate and pantothenate in stereotypy sensitization, and myo-inositol in margin time sensitization. Secondary analyses indicated that these associations were independent of concurrent methamphetamine levels and, with the exception of the myo-inositol association, suggest a mechanism whereby strain-based genetic variation produces specific baseline neurochemical differences that substantially influence the magnitude of MA-induced sensitization. These findings demonstrate the utility of mouse metabolomics for identifying novel biomarkers, and developing more comprehensive neurochemical models, of psychostimulant sensitization. PMID:24034544

  2. A Sensitivity Analysis Approach to Identify Key Environmental Performance Factors

    Directory of Open Access Journals (Sweden)

    Xi Yu

    2014-01-01

    Full Text Available Life cycle assessment (LCA is widely used in design phase to reduce the product’s environmental impacts through the whole product life cycle (PLC during the last two decades. The traditional LCA is restricted to assessing the environmental impacts of a product and the results cannot reflect the effects of changes within the life cycle. In order to improve the quality of ecodesign, it is a growing need to develop an approach which can reflect the changes between the design parameters and product’s environmental impacts. A sensitivity analysis approach based on LCA and ecodesign is proposed in this paper. The key environmental performance factors which have significant influence on the products’ environmental impacts can be identified by analyzing the relationship between environmental impacts and the design parameters. Users without much environmental knowledge can use this approach to determine which design parameter should be first considered when (redesigning a product. A printed circuit board (PCB case study is conducted; eight design parameters are chosen to be analyzed by our approach. The result shows that the carbon dioxide emission during the PCB manufacture is highly sensitive to the area of PCB panel.

  3. Method of identifying hairpin DNA probes by partial fold analysis

    Science.gov (United States)

    Miller, Benjamin L [Penfield, NY; Strohsahl, Christopher M [Saugerties, NY

    2009-10-06

    Method of identifying molecular beacons in which a secondary structure prediction algorithm is employed to identify oligonucleotide sequences within a target gene having the requisite hairpin structure. Isolated oligonucleotides, molecular beacons prepared from those oligonucleotides, and their use are also disclosed.

  4. BredeQuery: Coordinate-Based Meta-analytic Search of Neuroscientific Literature from the SPM Environment

    DEFF Research Database (Denmark)

    Wilkowski, Bartlomiej; Szewczyk, Marcin Marek; Rasmussen, Peter Mondrup

    2010-01-01

    Query offers a direct link from SPM to the Brede Database coordinate-based search engine. BredeQuery is able to ‘grab’ brain location coordinates from the SPM windows and enter them as a query for the Brede Database. Moreover, results of the query can be displayed in a MATLAB window and/or exported directly...... of the databases offer so-called coordinate-based searching to the users (e.g. Brede, BrainMap). For such search, the publications, which relate to the brain locations represented by the user coordinates, are retrieved. We present BredeQuery – a plugin for the widely used SPM data analytic pipeline. Brede...

  5. Results of SPM sun photometer measurements at Mirny Antarctic station (58-60th RAE)

    Science.gov (United States)

    Kabanov, Dmitry M.; Prakhov, Aleksander N.; Radionov, Vladimir F.; Sakerin, Sergey M.

    2015-11-01

    The SPM portable sun photometer observations in the wavelength range of 0.34-2.14 μm are performed at Mirny Antarctic station since fall 2013. The data obtained are used to calculate the aerosol optical depth (AOD) and water vapor content of the atmosphere. The sun photometer intercalibration results and statistical characteristics of interdiurnal and seasonal variations in spectral AOD of the atmosphere are discussed. Estimates of interannual variations in the atmospheric AOD in the region of Mirny station and in the coastal zone of Antarctica are presented. The global background level of AOD of the Antarctic atmosphere is noted to be still about 0.02 at the wavelength of 0.5 μm.

  6. Brain perfusion SPECT of patients with anorexia nervosa. Evaluation using statistical parametric mapping (SPM96)

    Energy Technology Data Exchange (ETDEWEB)

    Nakabeppu, Yoshiaki; Nakajoh, Masayuki; Tsuchimochi, Shinsaku; Tani, Atsushi; Umanodan, Tomokazu [Kagoshima Univ. (Japan). Faculty of Medicine; Naruo, Tetsuro; Nozoe, Shinichi

    2001-02-01

    Anorexia nervosa (AN) has two subtypes; restricting type (AN-R) and binge-eating/purging type (AN-BP). It is suggested that AN-R is different from AN-BP on psychopathological aspects. We compared regional cerebral blood flows of 7 female patients with AN-R, 7 female patients with AN-BP and 7 age-matched normal volunteers (NV) using Tc99m-HMPAO SPECT processed by SPM96. There were significant decreased perfusions in the anterior cingulate gyrus in AN-R when compared with those of AN-BP and NV. These results suggest that the mechanism of outbreak of AN-R may be different from that of AN-BP. (author)

  7. Brain perfusion SPECT of patients with anorexia nervosa. Evaluation using statistical parametric mapping (SPM96)

    International Nuclear Information System (INIS)

    Nakabeppu, Yoshiaki; Nakajoh, Masayuki; Tsuchimochi, Shinsaku; Tani, Atsushi; Umanodan, Tomokazu; Naruo, Tetsuro; Nozoe, Shinichi

    2001-01-01

    Anorexia nervosa (AN) has two subtypes; restricting type (AN-R) and binge-eating/purging type (AN-BP). It is suggested that AN-R is different from AN-BP on psychopathological aspects. We compared regional cerebral blood flows of 7 female patients with AN-R, 7 female patients with AN-BP and 7 age-matched normal volunteers (NV) using Tc99m-HMPAO SPECT processed by SPM96. There were significant decreased perfusions in the anterior cingulate gyrus in AN-R when compared with those of AN-BP and NV. These results suggest that the mechanism of outbreak of AN-R may be different from that of AN-BP. (author)

  8. Integrating subpathway analysis to identify candidate agents for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Wang J

    2016-03-01

    Full Text Available Jiye Wang,1 Mi Li,2 Yun Wang,3 Xiaoping Liu4 1The Criminal Science and Technology Department, Zhejiang Police College, Hangzhou, Zhejiang Province, 2Department of Nursing, Shandong College of Traditional Chinese Medicine College, Yantai, Shandong Province, 3Office Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiao Tong University, Xi’an, Shanxi Province, 4Key Laboratory of Systems Biology, Shanghai Institutes for Biological Sciences, Shanghai, People’s Republic of China Abstract: Hepatocellular carcinoma (HCC is the second most common cause of cancer-associated death worldwide, characterized by a high invasiveness and resistance to normal anticancer treatments. The need to develop new therapeutic agents for HCC is urgent. Here, we developed a bioinformatics method to identify potential novel drugs for HCC by integrating HCC-related and drug-affected subpathways. By using the RNA-seq data from the TCGA (The Cancer Genome Atlas database, we first identified 1,763 differentially expressed genes between HCC and normal samples. Next, we identified 104 significant HCC-related subpathways. We also identified the subpathways associated with small molecular drugs in the CMap database. Finally, by integrating HCC-related and drug-affected subpathways, we identified 40 novel small molecular drugs capable of targeting these HCC-involved subpathways. In addition to previously reported agents (ie, calmidazolium, our method also identified potentially novel agents for targeting HCC. We experimentally verified that one of these novel agents, prenylamine, induced HCC cell apoptosis using 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide, an acridine orange/ethidium bromide stain, and electron microscopy. In addition, we found that prenylamine not only affected several classic apoptosis-related proteins, including Bax, Bcl-2, and cytochrome c, but also increased caspase-3 activity. These candidate small molecular drugs

  9. Structural identifiability analysis of a cardiovascular system model.

    Science.gov (United States)

    Pironet, Antoine; Dauby, Pierre C; Chase, J Geoffrey; Docherty, Paul D; Revie, James A; Desaive, Thomas

    2016-05-01

    The six-chamber cardiovascular system model of Burkhoff and Tyberg has been used in several theoretical and experimental studies. However, this cardiovascular system model (and others derived from it) are not identifiable from any output set. In this work, two such cases of structural non-identifiability are first presented. These cases occur when the model output set only contains a single type of information (pressure or volume). A specific output set is thus chosen, mixing pressure and volume information and containing only a limited number of clinically available measurements. Then, by manipulating the model equations involving these outputs, it is demonstrated that the six-chamber cardiovascular system model is structurally globally identifiable. A further simplification is made, assuming known cardiac valve resistances. Because of the poor practical identifiability of these four parameters, this assumption is usual. Under this hypothesis, the six-chamber cardiovascular system model is structurally identifiable from an even smaller dataset. As a consequence, parameter values computed from limited but well-chosen datasets are theoretically unique. This means that the parameter identification procedure can safely be performed on the model from such a well-chosen dataset. Thus, the model may be considered suitable for use in diagnosis. Copyright © 2016 IPEM. Published by Elsevier Ltd. All rights reserved.

  10. Use of Photogrammetry and Biomechanical Gait analysis to Identify Individuals

    DEFF Research Database (Denmark)

    Larsen, Peter Kastmand; Simonsen, Erik Bruun; Lynnerup, Niels

    Photogrammetry and recognition of gait patterns are valuable tools to help identify perpetrators based on surveillance recordings. We have found that stature but only few other measures have a satisfying reproducibility for use in forensics. Several gait variables with high recognition rates were...

  11. Gene expression analysis identifies global gene dosage sensitivity in cancer

    DEFF Research Database (Denmark)

    Fehrmann, Rudolf S. N.; Karjalainen, Juha M.; Krajewska, Malgorzata

    2015-01-01

    Many cancer-associated somatic copy number alterations (SCNAs) are known. Currently, one of the challenges is to identify the molecular downstream effects of these variants. Although several SCNAs are known to change gene expression levels, it is not clear whether each individual SCNA affects gen...

  12. Identifying clinical course patterns in SMS data using cluster analysis

    DEFF Research Database (Denmark)

    Kent, Peter; Kongsted, Alice

    2012-01-01

    ABSTRACT: BACKGROUND: Recently, there has been interest in using the short message service (SMS or text messaging), to gather frequent information on the clinical course of individual patients. One possible role for identifying clinical course patterns is to assist in exploring clinically importa...

  13. Integrated Analysis Identifies Interaction Patterns between Small Molecules and Pathways

    Science.gov (United States)

    Li, Yan; Li, Weiguo; Chen, Xin; Sun, Jiatong; Chen, Huan; Lv, Sali

    2014-01-01

    Previous studies have indicated that the downstream proteins in a key pathway can be potential drug targets and that the pathway can play an important role in the action of drugs. So pathways could be considered as targets of small molecules. A link map between small molecules and pathways was constructed using gene expression profile, pathways, and gene expression of cancer cell line intervened by small molecules and then we analysed the topological characteristics of the link map. Three link patterns were identified based on different drug discovery implications for breast, liver, and lung cancer. Furthermore, molecules that significantly targeted the same pathways tended to treat the same diseases. These results can provide a valuable reference for identifying drug candidates and targets in molecularly targeted therapy. PMID:25114931

  14. Association analysis identifies ZNF750 regulatory variants in psoriasis

    Directory of Open Access Journals (Sweden)

    Birnbaum Ramon Y

    2011-12-01

    Full Text Available Abstract Background Mutations in the ZNF750 promoter and coding regions have been previously associated with Mendelian forms of psoriasis and psoriasiform dermatitis. ZNF750 encodes a putative zinc finger transcription factor that is highly expressed in keratinocytes and represents a candidate psoriasis gene. Methods We examined whether ZNF750 variants were associated with psoriasis in a large case-control population. We sequenced the promoter and exon regions of ZNF750 in 716 Caucasian psoriasis cases and 397 Caucasian controls. Results We identified a total of 47 variants, including 38 rare variants of which 35 were novel. Association testing identified two ZNF750 haplotypes associated with psoriasis (p ZNF750 promoter and 5' UTR variants displayed a 35-55% reduction of ZNF750 promoter activity, consistent with the promoter activity reduction seen in a Mendelian psoriasis family with a ZNF750 promoter variant. However, the rare promoter and 5' UTR variants identified in this study did not strictly segregate with the psoriasis phenotype within families. Conclusions Two haplotypes of ZNF750 and rare 5' regulatory variants of ZNF750 were found to be associated with psoriasis. These rare 5' regulatory variants, though not causal, might serve as a genetic modifier of psoriasis.

  15. Using Factor Analysis to Identify Topic Preferences Within MBA Courses

    Directory of Open Access Journals (Sweden)

    Earl Chrysler

    2003-02-01

    Full Text Available This study demonstrates the role of a principal components factor analysis in conducting a gap analysis as to the desired characteristics of business alumni. Typically, gap analyses merely compare the emphases that should be given to areas of inquiry with perceptions of actual emphases. As a result, the focus is upon depth of coverage. A neglected area in need of investigation is the breadth of topic dimensions and their differences between the normative (should offer and the descriptive (actually offer. The implications of factor structures, as well as traditional gap analyses, are developed and discussed in the context of outcomes assessment.

  16. Using Linguistic Analysis to Identify High Performing Teams

    Science.gov (United States)

    2006-06-01

    used in two studies. Specifically, participants were told: Many people have made an extensive analysis into the effects of overpopulation , chemical... pollution , and air and water pollution . A frequent conclusion is that the next 5 to 10 years are critical because if significant changes in our society

  17. Evaluation of energy system analysis techniques for identifying underground facilities

    Energy Technology Data Exchange (ETDEWEB)

    VanKuiken, J.C.; Kavicky, J.A.; Portante, E.C. [and others

    1996-03-01

    This report describes the results of a study to determine the feasibility and potential usefulness of applying energy system analysis techniques to help detect and characterize underground facilities that could be used for clandestine activities. Four off-the-shelf energy system modeling tools were considered: (1) ENPEP (Energy and Power Evaluation Program) - a total energy system supply/demand model, (2) ICARUS (Investigation of Costs and Reliability in Utility Systems) - an electric utility system dispatching (or production cost and reliability) model, (3) SMN (Spot Market Network) - an aggregate electric power transmission network model, and (4) PECO/LF (Philadelphia Electric Company/Load Flow) - a detailed electricity load flow model. For the purposes of most of this work, underground facilities were assumed to consume about 500 kW to 3 MW of electricity. For some of the work, facilities as large as 10-20 MW were considered. The analysis of each model was conducted in three stages: data evaluation, base-case analysis, and comparative case analysis. For ENPEP and ICARUS, open source data from Pakistan were used for the evaluations. For SMN and PECO/LF, the country data were not readily available, so data for the state of Arizona were used to test the general concept.

  18. PETPVE12: an SPM toolbox for Partial Volume Effects correction in brain PET - Application to amyloid imaging with AV45-PET.

    Science.gov (United States)

    Gonzalez-Escamilla, Gabriel; Lange, Catharina; Teipel, Stefan; Buchert, Ralph; Grothe, Michel J

    2017-02-15

    Positron emission tomography (PET) allows detecting molecular brain changes in vivo. However, the accuracy of PET is limited by partial volume effects (PVE) that affects quantitative analysis and visual interpretation of the images. Although PVE-correction methods have been shown to effectively increase the correspondence of the measured signal with the true regional tracer uptake, these procedures are still not commonly applied, neither in clinical nor in research settings. Here, we present an implementation of well validated PVE-correction procedures as a SPM toolbox, PETPVE12, for automated processing. We demonstrate its utility by a comprehensive analysis of the effects of PVE-correction on amyloid-sensitive AV45-PET data from 85 patients with Alzheimer's disease (AD) and 179 cognitively normal (CN) elderly. Effects of PVE-correction on global cortical standard uptake value ratios (SUVR) and the power of diagnostic group separation were assessed for the region-wise geometric transfer matrix method (PVEc-GTM), as well as for the 3-compartmental voxel-wise "Müller-Gärtner" method (PVEc-MG). Both PVE-correction methods resulted in decreased global cortical SUVRs in the low to middle range of SUVR values, and in increased global cortical SUVRs at the high values. As a consequence, average SUVR of the CN group was reduced, whereas average SUVR of the AD group was increased by PVE-correction. These effects were also reflected in increased accuracies of group discrimination after PVEc-GTM (AUC=0.86) and PVEc-MG (AUC=0.89) compared to standard non-corrected SUVR (AUC=0.84). Voxel-wise analyses of PVEc-MG corrected data also demonstrated improved detection of regionally increased AV45 SUVR values in AD patients. These findings complement the growing evidence for a beneficial effect of PVE-correction in quantitative analysis of amyloid-sensitive PET data. The novel PETPVE12 toolbox significantly facilitates the application of PVE-correction, particularly within SPM

  19. The SpmA/B and DacF proteins of Clostridium perfringens play important roles in spore heat resistance.

    Science.gov (United States)

    Orsburn, Benjamin; Sucre, Katie; Popham, David L; Melville, Stephen B

    2009-02-01

    Strains of Clostridium perfringens that cause acute food poisoning have been shown to produce spores that are significantly more heat resistant than those of other strains. Previous studies demonstrated that the spore core density and the ratio of spore cortex peptidoglycan relative to the germ cell wall were factors that correlated with the heat resistance of a C. perfringens spore. To further evaluate these relationships, mutant strains of C. perfringens SM101 were constructed with null mutations in dacF, encoding a D,D-carboxypeptidase, and in the spmA-spmB operon, which is involved in spore core dehydration. The dacF mutant was shown to produce less spore cortex peptidoglycan and had a corresponding decrease in spore heat resistance. The spmA-spmB strain produced highly unstable spores with significantly lower core densities and increased heat sensitivity, which were easily destroyed during treatments affecting the spore coat layers. These results support the previous assertion that a threshold core density as well as a high ratio of cortex peptidoglycan relative to the germ cell wall contribute to the formation of a more heat-resistant spore in this species.

  20. Compartmental analysis of dynamic nuclear medicine data: models and identifiability

    Science.gov (United States)

    Delbary, Fabrice; Garbarino, Sara; Vivaldi, Valentina

    2016-12-01

    Compartmental models based on tracer mass balance are extensively used in clinical and pre-clinical nuclear medicine in order to obtain quantitative information on tracer metabolism in the biological tissue. This paper is the first of a series of two that deal with the problem of tracer coefficient estimation via compartmental modelling in an inverse problem framework. Specifically, here we discuss the identifiability problem for a general n-dimension compartmental system and provide uniqueness results in the case of two-compartment and three-compartment compartmental models. The second paper will utilize this framework in order to show how nonlinear regularization schemes can be applied to obtain numerical estimates of the tracer coefficients in the case of nuclear medicine data corresponding to brain, liver and kidney physiology.

  1. Chemical analysis of a new kinematically identified stellar group .

    Science.gov (United States)

    Ženovienė, R.; Tautvaišienė, G.; Nordström, B.; Stonkutė, E.

    We have started a study of chemical composition of a new kinematically identified group of stars in the Galactic disc. Based on dynamical properties those stars were suspected to belong to a disrupted satellite. The main atmospheric parameters and chemical composition were determined for thirty-two stars from high resolution spectra obtained at the Nordic Optical Telescope with the spectrograph FIES. In this contribution the preliminary results of chemical composition study are presented. The metallicity of the investigated stars lie in the interval -0.2 < [Fe/H] < -0.6, their abundances of oxygen and alpha-elements are overabundant in comparison to the Galactic thin disc dwarfs at this metallicity range. This provides further evidences of their common and possibly extragalactic origin.

  2. Association analysis identifies 65 new breast cancer risk loci

    DEFF Research Database (Denmark)

    Michailidou, Kyriaki; Lindström, Sara; Dennis, Joe

    2017-01-01

    cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P risk single-nucleotide polymorphisms in these loci fall......Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast......-nucleotide polymorphisms in regulatory features was 2-5-fold enriched relative to the genome-wide average, with strong enrichment for particular transcription factor binding sites. These results provide further insight into genetic susceptibility to breast cancer and will improve the use of genetic risk scores...

  3. Monoallelic mutation analysis (MAMA) for identifying germline mutations.

    Science.gov (United States)

    Papadopoulos, N; Leach, F S; Kinzler, K W; Vogelstein, B

    1995-09-01

    Dissection of germline mutations in a sensitive and specific manner presents a continuing challenge. In dominantly inherited diseases, mutations occur in only one allele and are often masked by the normal allele. Here we report the development of a sensitive and specific diagnostic strategy based on somatic cell hybridization termed MAMA (monoallelic mutation analysis). We have demonstrated the utility of this strategy in two different hereditary colorectal cancer syndromes, one caused by a defective tumour suppressor gene on chromosome 5 (familial adenomatous polyposis, FAP) and the other caused by a defective mismatch repair gene on chromosome 2 (hereditary non-polyposis colorectal cancer, HNPCC).

  4. Genetic analysis of CHARGE syndrome identifies overlapping molecular biology.

    Science.gov (United States)

    Moccia, Amanda; Srivastava, Anshika; Skidmore, Jennifer M; Bernat, John A; Wheeler, Marsha; Chong, Jessica X; Nickerson, Deborah; Bamshad, Michael; Hefner, Margaret A; Martin, Donna M; Bielas, Stephanie L

    2018-01-04

    PurposeCHARGE syndrome is an autosomal-dominant, multiple congenital anomaly condition characterized by vision and hearing loss, congenital heart disease, and malformations of craniofacial and other structures. Pathogenic variants in CHD7, encoding adenosine triphosphate-dependent chromodomain helicase DNA binding protein 7, are present in the majority of affected individuals. However, no causal variant can be found in 5-30% (depending on the cohort) of individuals with a clinical diagnosis of CHARGE syndrome.MethodsWe performed whole-exome sequencing (WES) on 28 families from which at least one individual presented with features highly suggestive of CHARGE syndrome.ResultsPathogenic variants in CHD7 were present in 15 of 28 individuals (53.6%), whereas 4 (14.3%) individuals had pathogenic variants in other genes (RERE, KMT2D, EP300, or PUF60). A variant of uncertain clinical significance in KDM6A was identified in one (3.5%) individual. The remaining eight (28.6%) individuals were not found to have pathogenic variants by WES.ConclusionThese results demonstrate that the phenotypic features of CHARGE syndrome overlap with multiple other rare single-gene syndromes. Additionally, they implicate a shared molecular pathology that disrupts epigenetic regulation of multiple-organ development.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.233.

  5. Immunogenicity of novel Dengue virus epitopes identified by bioinformatic analysis.

    Science.gov (United States)

    Sánchez-Burgos, Gilma; Ramos-Castañeda, José; Cedillo-Rivera, Roberto; Dumonteil, Eric

    2010-10-01

    We used T cell epitope prediction tools to identify epitopes from Dengue virus polyprotein sequences, and evaluated in vivo and in vitro the immunogenicity and antigenicity of the corresponding synthetic vaccine candidates. Twenty-two epitopes were predicted to have a high affinity for MHC class I (H-2Kd, H-2Dd, H-2Ld alleles) or class II (IAd alleles). These epitopes were conserved between the four virus serotypes, but with no similarity to human and mouse sequences. Thirteen synthetic peptides induced specific antibodies production with or without T cells activation in mice. Three synthetic peptides induced mostly IgG antibodies, and one of these from the E gene induced a neutralizing response. Ten peptides induced a combination of humoral and cellular responses by CD4+ and CD8+ T cells. Twelve peptides were novel B and T cell epitopes. These results indicate that our bioinformatics strategy is a powerful tool for the identification of novel antigens and its application to human HLA may lead to a potent epitope-based vaccine against Dengue virus and many other pathogens. (c) 2010 Elsevier B.V. All rights reserved.

  6. Identifying a preservation zone using multicriteria decision analysis

    Energy Technology Data Exchange (ETDEWEB)

    Farashi, A.; Naderi, M.; Parvian, N.

    2016-07-01

    Zoning of a protected area is an approach to partition landscape into various land use units. The management of these landscape units can reduce conflicts caused by human activities. Tandoreh National Park is one of the most biologically diverse, protected areas in Iran. Although the area is generally designed to protect biodiversity, there are many conflicts between biodiversity conservation and human activities. For instance, the area is highly controversial and has been considered as an impediment to local economic development, such as tourism, grazing, road construction, and cultivation. In order to reduce human conflicts with biodiversity conservation in Tandoreh National Park, safe zones need to be established and human activities need to be moved out of the zones. In this study we used a systematic methodology to integrate a participatory process with Geographic Information Systems (GIS) using a multi–criteria decision analysis (MCDA) technique to guide a zoning scheme for the Tandoreh National Park, Iran. Our results show that the northern and eastern parts of the Tandoreh National Park that were close to rural areas and farmlands returned less desirability for selection as a preservation area. Rocky Mountains were the most important and most destructed areas and abandoned plains were the least important criteria for preservation in the area. Furthermore, the results reveal that the land properties were considered to be important for protection based on the obtaine. (Author)

  7. Identifying a preservation zone using multi–criteria decision analysis

    Directory of Open Access Journals (Sweden)

    Farashi, A.

    2016-03-01

    Full Text Available Zoning of a protected area is an approach to partition landscape into various land use units. The management of these landscape units can reduce conflicts caused by human activities. Tandoreh National Park is one of the most biologically diverse, protected areas in Iran. Although the area is generally designed to protect biodiversity, there are many conflicts between biodiversity conservation and human activities. For instance, the area is highly controversial and has been considered as an impediment to local economic development, such as tourism, grazing, road construction, and cultivation. In order to reduce human conflicts with biodiversity conservation in Tandoreh National Park, safe zones need to be established and human activities need to be moved out of the zones. In this study we used a systematic methodology to integrate a participatory process with Geographic Information Systems (GIS using a multi–criteria decision analysis (MCDA technique to guide a zoning scheme for the Tandoreh National Park, Iran. Our results show that the northern and eastern parts of the Tandoreh National Park that were close to rural areas and farmlands returned less desirability for selection as a preservation area. Rocky Mountains were the most important and most destructed areas and abandoned plains were the least important criteria for preservation in the area. Furthermore, the results reveal that the land properties were considered to be important for protection based on the obtaine

  8. Meconium microbiome analysis identifies bacteria correlated with premature birth.

    Directory of Open Access Journals (Sweden)

    Alexandria N Ardissone

    Full Text Available Preterm birth is the second leading cause of death in children under the age of five years worldwide, but the etiology of many cases remains enigmatic. The dogma that the fetus resides in a sterile environment is being challenged by recent findings and the question has arisen whether microbes that colonize the fetus may be related to preterm birth. It has been posited that meconium reflects the in-utero microbial environment. In this study, correlations between fetal intestinal bacteria from meconium and gestational age were examined in order to suggest underlying mechanisms that may contribute to preterm birth.Meconium from 52 infants ranging in gestational age from 23 to 41 weeks was collected, the DNA extracted, and 16S rRNA analysis performed. Resulting taxa of microbes were correlated to clinical variables and also compared to previous studies of amniotic fluid and other human microbiome niches.Increased detection of bacterial 16S rRNA in meconium of infants of <33 weeks gestational age was observed. Approximately 61·1% of reads sequenced were classified to genera that have been reported in amniotic fluid. Gestational age had the largest influence on microbial community structure (R = 0·161; p = 0·029, while mode of delivery (C-section versus vaginal delivery had an effect as well (R = 0·100; p = 0·044. Enterobacter, Enterococcus, Lactobacillus, Photorhabdus, and Tannerella, were negatively correlated with gestational age and have been reported to incite inflammatory responses, suggesting a causative role in premature birth.This provides the first evidence to support the hypothesis that the fetal intestinal microbiome derived from swallowed amniotic fluid may be involved in the inflammatory response that leads to premature birth.

  9. Validation of the new trapped environment AE9/AP9/SPM at low Earth orbit

    Science.gov (United States)

    Badavi, Francis F.

    2014-09-01

    The completion of the international space station (ISS) in 2011 has provided the space research community an ideal proving ground for future long duration human activities in space. Ionizing radiation measurements in ISS form the ideal tool for the validation of radiation environmental models, nuclear transport codes and nuclear reaction cross sections. Indeed, prior measurements on the space transportation system (STS; shuttle) provided vital information impacting both the environmental models and the nuclear transport code developments by indicating the need for an improved dynamic model of the low Earth orbit (LEO) trapped environment. Additional studies using thermo-luminescent detector (TLD), tissue equivalent proportional counter (TEPC) area monitors, and computer aided design (CAD) model of earlier ISS configurations, confirmed STS observations that, as input, computational dosimetry requires an environmental model with dynamic and directional (anisotropic) behavior, as well as an accurate six degree of freedom (DOF) definition of the vehicle attitude and orientation along the orbit of ISS. At LEO, a vehicle encounters exposure from trapped particles and attenuated galactic cosmic rays (GCR). Within the trapped field, a challenge arises from properly estimating the amount of exposure acquired. There exist a number of models to define the intensities of the trapped particles during the solar quiet and active times. At active times, solar energetic particles (SEP) generated by solar flare or coronal mass ejection (CME) also contribute to the exposure at high northern and southern latitudes. Among the more established trapped models are the historic and popular AE8/AP8, dating back to the 1980s, the historic and less popular CRRES electron/proton, dating back to 1990s and the recently released AE9/AP9/SPM. The AE9/AP9/SPM model is a major improvement over the older AE8/AP8 and CRRES models. This model is derived from numerous measurements acquired over four

  10. Analysis of 18F-FDG PET mapping in malignant tumor patients with depression by SPM

    International Nuclear Information System (INIS)

    Su Liang; Zuo Chuantao; Guan Yihui; Zhao Jun; Shi Shenxun

    2005-01-01

    Objective: To investigate brain 18 F-fluorodeoxyglucose (FDG) PET mapping in malignant tumor patients with depressive emotion. Methods: 18 F-FDG PET imaging was performed in 21 malignant tumor patients (tumor group) and 21 healthy controls (control group). All were evaluated by self-rating depression scale (SDS)and 24 questions Hamilton rating scale for depression (HAMD). Results: (1) The standard total score of SDS and HAMD of the tumor group were higher than those of the control group (P 18 F-FDG PET imagings. The abnormalities of glucose metabolism might be related to their depressive emotion. (authors)

  11. Roles of DacB and spm proteins in clostridium perfringens spore resistance to moist heat, chemicals, and UV radiation.

    Science.gov (United States)

    Paredes-Sabja, Daniel; Sarker, Nahid; Setlow, Barbara; Setlow, Peter; Sarker, Mahfuzur R

    2008-06-01

    Clostridium perfringens food poisoning is caused mainly by enterotoxigenic type A isolates that typically possess high spore heat resistance. Previous studies have shown that alpha/beta-type small, acid-soluble proteins (SASP) play a major role in the resistance of Bacillus subtilis and C. perfringens spores to moist heat, UV radiation, and some chemicals. Additional major factors in B. subtilis spore resistance are the spore's core water content and cortex peptidoglycan (PG) structure, with the latter properties modulated by the spm and dacB gene products and the sporulation temperature. In the current work, we have shown that the spm and dacB genes are expressed only during C. perfringens sporulation and have examined the effects of spm and dacB mutations and sporulation temperature on spore core water content and spore resistance to moist heat, UV radiation, and a number of chemicals. The results of these analyses indicate that for C. perfringens SM101 (i) core water content and, probably, cortex PG structure have little if any role in spore resistance to UV and formaldehyde, presumably because these spores' DNA is saturated with alpha/beta-type SASP; (ii) spore resistance to moist heat and nitrous acid is determined to a large extent by core water content and, probably, cortex structure; (iii) core water content and cortex PG cross-linking play little or no role in spore resistance to hydrogen peroxide; (iv) spore core water content decreases with higher sporulation temperatures, resulting in spores that are more resistant to moist heat; and (v) factors in addition to SpmAB, DacB, and sporulation temperature play roles in determining spore core water content and thus, spore resistance to moist heat.

  12. Expression of ODC1, SPD, SPM and AZIN1 in the hypothalamus, ovary and uterus during rat estrous cycle.

    Science.gov (United States)

    Fernandes, Joseph R D; Jain, Sammit; Banerjee, Arnab

    2017-05-15

    The aim of the present study was to investigate variation in the expression pattern of ornithine decarboxylase (ODC1), spermine (SPM), spermidine (SPD) and antizyme inhibitor (AZIN1) in hypothalamus, ovary and uterus during the estrous cycle of rats. Further, to understand any correlation between polyamines and GnRH I expression in hypothalamus; effect of putrescine treatment on GnRH I expression in hypothalamus and progesterone and estradiol levels in serum were investigated. The study also aims in quantifying all the immunohistochemistry images obtained based on pixel counting algorithm to yield the relative pixel count. This algorithm uses a red green blue (RGB) colour thresholding approach to quantify the intensity of the chromogen present. The result of the present study demonstrates almost similar expression pattern of polyamine and polyamine related factors, ODC1, SPD, SPM and AZIN1, with that of hypothalamic GnRH I, all of which mainly localized in the medial preoptic area (MPA) of the hypothalamus, during the proestrus, estrus and diestrus. This suggest that hypothalamic GnRH I expression is under regulation of polyamines. The study showed significant increase in hypothalamic GnRH I expression for both the doses of putrescine treatment to adult female rats. Further, it was shown that in ovary expression pattern of ODC1, SPM, SPD and AZIN1 were similar with that of steroidogenic factor, StAR during the estrous cycle, and putrescine supplementation increased significantly estradiol and progesterone levels in serum, all suggesting ovarian polyamines are involved in regulation of ovarian steroidogenesis. Localization of these factors in the theca and granulosa cells suggest involvement of polyamines in the process of folliculogenesis and luteinization; and ODC1, SPD, SPM and AZIN1 in oocyte further suggests polyamine role in maintenance of oocyte physiology. Finally, in uterus SPM and AZIN1 were localized throughout the estrous cycle, being comparatively more

  13. Assessing Reliability of Cellulose Hydrolysis Models to Support Biofuel Process Design – Identifiability and Uncertainty Analysis

    DEFF Research Database (Denmark)

    Sin, Gürkan; Meyer, Anne S.; Gernaey, Krist

    2010-01-01

    The reliability of cellulose hydrolysis models is studied using the NREL model. An identifiability analysis revealed that only 6 out of 26 parameters are identifiable from the available data (typical hydrolysis experiments). Attempting to identify a higher number of parameters (as done in the ori......The reliability of cellulose hydrolysis models is studied using the NREL model. An identifiability analysis revealed that only 6 out of 26 parameters are identifiable from the available data (typical hydrolysis experiments). Attempting to identify a higher number of parameters (as done...

  14. Development of a Micro-SPM (Scanning Probe Microscope by Post-Assembly of a MEMS-Stage and an Independent Cantilever

    Directory of Open Access Journals (Sweden)

    Zhi Li

    2007-08-01

    Full Text Available The development of miniature scanning probe microscopes (SPM on the basis of the MEMS technique has gained more and more interest. Here a novel approach is presented to realize a micro-SPM, in which by means of post-assembly a conventional cantilever is mounted onto a MEMS positioning stage and used to detect the topography variation of the surface under test. Compared with other integrated micro-SPMs, the proposed micro-SPM can maintain the lateral resolution by simply renewing its cantilever in use, and therefore features low cost, practicability and longer lifetime. Preliminary experimental results are reported, which demonstrate that the proposed microSPM can be realized.

  15. A force profile analysis comparison between functional data analysis, statistical parametric mapping and statistical non-parametric mapping in on-water single sculling.

    Science.gov (United States)

    Warmenhoven, John; Harrison, Andrew; Robinson, Mark A; Vanrenterghem, Jos; Bargary, Norma; Smith, Richard; Cobley, Stephen; Draper, Conny; Donnelly, Cyril; Pataky, Todd

    2018-03-21

    To examine whether the Functional Data Analysis (FDA), Statistical Parametric Mapping (SPM) and Statistical non-Parametric Mapping (SnPM) hypothesis testing techniques differ in their ability to draw inferences in the context of a single, simple experimental design. The sample data used is cross-sectional (two-sample gender comparison) and evaluation of differences between statistical techniques used a combination of descriptive and qualitative assessments. FDA, SPM and SnPM t-tests were applied to sample data of twenty highly skilled male and female rowers, rowing at 32 strokes per minute in a single scull boat. Statistical differences for gender were assessed by applying two t-tests (one for each side of the boat). The t-statistic values were identical for all three methods (with the FDA t-statistic presented as an absolute measure). The critical t-statistics (t crit ) were very similar between the techniques, with SPM t crit providing a marginally higher t crit than the FDA and SnPM t crit values (which were identical). All techniques were successful in identifying consistent sections of the force waveform, where male and female rowers were shown to differ significantly (pparametric assumption of SPM, as well as contextual factors related to the type of waveform data to be analysed and the experimental research question of interest. Copyright © 2018. Published by Elsevier Ltd.

  16. Vector field statistical analysis of kinematic and force trajectories.

    Science.gov (United States)

    Pataky, Todd C; Robinson, Mark A; Vanrenterghem, Jos

    2013-09-27

    When investigating the dynamics of three-dimensional multi-body biomechanical systems it is often difficult to derive spatiotemporally directed predictions regarding experimentally induced effects. A paradigm of 'non-directed' hypothesis testing has emerged in the literature as a result. Non-directed analyses typically consist of ad hoc scalar extraction, an approach which substantially simplifies the original, highly multivariate datasets (many time points, many vector components). This paper describes a commensurately multivariate method as an alternative to scalar extraction. The method, called 'statistical parametric mapping' (SPM), uses random field theory to objectively identify field regions which co-vary significantly with the experimental design. We compared SPM to scalar extraction by re-analyzing three publicly available datasets: 3D knee kinematics, a ten-muscle force system, and 3D ground reaction forces. Scalar extraction was found to bias the analyses of all three datasets by failing to consider sufficient portions of the dataset, and/or by failing to consider covariance amongst vector components. SPM overcame both problems by conducting hypothesis testing at the (massively multivariate) vector trajectory level, with random field corrections simultaneously accounting for temporal correlation and vector covariance. While SPM has been widely demonstrated to be effective for analyzing 3D scalar fields, the current results are the first to demonstrate its effectiveness for 1D vector field analysis. It was concluded that SPM offers a generalized, statistically comprehensive solution to scalar extraction's over-simplification of vector trajectories, thereby making it useful for objectively guiding analyses of complex biomechanical systems. © 2013 Published by Elsevier Ltd. All rights reserved.

  17. Identifying Students at Risk: An Examination of Computer-Adaptive Measures and Latent Class Growth Analysis

    Science.gov (United States)

    Keller-Margulis, Milena; McQuillin, Samuel D.; Castañeda, Juan Javier; Ochs, Sarah; Jones, John H.

    2018-01-01

    Multitiered systems of support depend on screening technology to identify students at risk. The purpose of this study was to examine the use of a computer-adaptive test and latent class growth analysis (LCGA) to identify students at risk in reading with focus on the use of this methodology to characterize student performance in screening.…

  18. Identifying At-Risk Students in General Chemistry via Cluster Analysis of Affective Characteristics

    Science.gov (United States)

    Chan, Julia Y. K.; Bauer, Christopher F.

    2014-01-01

    The purpose of this study is to identify academically at-risk students in first-semester general chemistry using affective characteristics via cluster analysis. Through the clustering of six preselected affective variables, three distinct affective groups were identified: low (at-risk), medium, and high. Students in the low affective group…

  19. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

    NARCIS (Netherlands)

    Schunkert, Heribert; König, Inke R.; Kathiresan, Sekar; Reilly, Muredach P.; Assimes, Themistocles L.; Holm, Hilma; Preuss, Michael; Stewart, Alexandre F. R.; Barbalic, Maja; Gieger, Christian; Absher, Devin; Aherrahrou, Zouhair; Allayee, Hooman; Altshuler, David; Anand, Sonia S.; Andersen, Karl; Anderson, Jeffrey L.; Ardissino, Diego; Ball, Stephen G.; Balmforth, Anthony J.; Barnes, Timothy A.; Becker, Diane M.; Becker, Lewis C.; Berger, Klaus; Bis, Joshua C.; Boekholdt, S. Matthijs; Boerwinkle, Eric; Braund, Peter S.; Brown, Morris J.; Burnett, Mary Susan; Buysschaert, Ian; Carlquist, John F.; Chen, Li; Cichon, Sven; Codd, Veryan; Davies, Robert W.; Dedoussis, George; Dehghan, Abbas; Demissie, Serkalem; Devaney, Joseph M.; Diemert, Patrick; Do, Ron; Doering, Angela; Eifert, Sandra; Mokhtari, Nour Eddine El; Ellis, Stephen G.; Elosua, Roberto; Engert, James C.; Epstein, Stephen E.; de Faire, Ulf; Fischer, Marcus; Folsom, Aaron R.; Freyer, Jennifer; Gigante, Bruna; Girelli, Domenico; Gretarsdottir, Solveig; Gudnason, Vilmundur; Gulcher, Jeffrey R.; Halperin, Eran; Hammond, Naomi; Hazen, Stanley L.; Hofman, Albert; Horne, Benjamin D.; Illig, Thomas; Iribarren, Carlos; Jones, Gregory T.; Jukema, J. Wouter; Kaiser, Michael A.; Kaplan, Lee M.; Kastelein, John J. P.; Khaw, Kay-Tee; Knowles, Joshua W.; Kolovou, Genovefa; Kong, Augustine; Laaksonen, Reijo; Lambrechts, Diether; Leander, Karin; Lettre, Guillaume; Li, Mingyao; Lieb, Wolfgang; Loley, Christina; Lotery, Andrew J.; Mannucci, Pier M.; Maouche, Seraya; Martinelli, Nicola; McKeown, Pascal P.; Meisinger, Christa; Meitinger, Thomas; Melander, Olle; Merlini, Pier Angelica; Mooser, Vincent; Morgan, Thomas; Mühleisen, Thomas W.; Muhlestein, Joseph B.; Münzel, Thomas; Musunuru, Kiran; Nahrstaedt, Janja; Nelson, Christopher P.; Nöthen, Markus M.; Olivieri, Oliviero; Patel, Riyaz S.; Patterson, Chris C.; Peters, Annette; Peyvandi, Flora; Qu, Liming; Quyyumi, Arshed A.; Rader, Daniel J.; Rallidis, Loukianos S.; Rice, Catherine; Rosendaal, Frits R.; Rubin, Diana; Salomaa, Veikko; Sampietro, M. Lourdes; Sandhu, Manj S.; Schadt, Eric; Schäfer, Arne; Schillert, Arne; Schreiber, Stefan; Schrezenmeir, Jürgen; Schwartz, Stephen M.; Siscovick, David S.; Sivananthan, Mohan; Sivapalaratnam, Suthesh; Smith, Albert; Smith, Tamara B.; Snoep, Jaapjan D.; Soranzo, Nicole; Spertus, John A.; Stark, Klaus; Stirrups, Kathy; Stoll, Monika; Tang, W. H. Wilson; Tennstedt, Stephanie; Thorgeirsson, Gudmundur; Thorleifsson, Gudmar; Tomaszewski, Maciej; Uitterlinden, Andre G.; van Rij, Andre M.; Voight, Benjamin F.; Wareham, Nick J.; Wells, George A.; Wichmann, H.-Erich; Wild, Philipp S.; Willenborg, Christina; Witteman, Jaqueline C. M.; Wright, Benjamin J.; Ye, Shu; Zeller, Tanja; Ziegler, Andreas; Cambien, Francois; Goodall, Alison H.; Cupples, L. Adrienne; Quertermous, Thomas; März, Winfried; Hengstenberg, Christian; Blankenberg, Stefan; Ouwehand, Willem H.; Hall, Alistair S.; Deloukas, Panos; Thompson, John R.; Stefansson, Kari; Roberts, Robert; Thorsteinsdottir, Unnur; O'Donnell, Christopher J.; McPherson, Ruth; Erdmann, Jeanette; Samani, Nilesh J.

    2011-01-01

    We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13

  20. Molecular detection of metallo-β-lactamase genes, bla IMP-1, bla VIM-2 and bla SPM-1 in imipenem resistant Pseudomonas aeruginosa isolated from clinical specimens in teaching hospitals of Ahvaz, Iran.

    Science.gov (United States)

    Moosavian, Mojtaba; Rahimzadeh, Mohammad

    2015-02-01

    Carbapenem resistant Pseudomonas aeruginosa is a serious cause of nosocomial infections. The main purpose of the study is to determine the prevalence rate of imipenem resistant Pseudomonas aeruginosa carrying metallo-ß-lactamase (MBL) genes. 236 Pseudomonas aeruginosa isolates were collected from teaching hospitals of Ahvaz University of Medical Sciences during a period of 9 months in 2012. These strains were identified using conventional microbiological tests. The susceptibility of isolates to antibiotics were assessed using disk diffusion test. The IMP-EDTA combination disk phenotypic test was performed for detection of MBL producing strains. Finally, polymerase chain reaction (PCR) was performed to detect MBL genes, bla IMP-1, bla VIM-2 and bla SPM-1 in imipenem resistant strains. Out of 236 examined isolates, 122 isolates (51.4%) were resistant to imipenem. The IMP-EDTA combination test showed that among 122 imipenem resistant strains, 110 strains (90%) were phenotipically MBL producers. Additionally, the results of PCR method showed that 2 strains (1.6%) and 67strains (55%) of imipenem resistant Pseudomonas aeruginosa isolates contained bla VIM-2 and bla IMP-1 genes respectively. No SPM-1gene was found in the examined samples. Resistance of P. aeruginosa isolates to imipenem due to MBL enzymes is increasing in Ahavaz. Because of clinical significance of this kind of resistance, rapid detection of MBL producing strains and followed by appropriate treatment is necessary to prevent the spreading of these organisms.

  1. Identifying influential individuals on intensive care units: using cluster analysis to explore culture.

    Science.gov (United States)

    Fong, Allan; Clark, Lindsey; Cheng, Tianyi; Franklin, Ella; Fernandez, Nicole; Ratwani, Raj; Parker, Sarah Henrickson

    2017-07-01

    The objective of this paper is to identify attribute patterns of influential individuals in intensive care units using unsupervised cluster analysis. Despite the acknowledgement that culture of an organisation is critical to improving patient safety, specific methods to shift culture have not been explicitly identified. A social network analysis survey was conducted and an unsupervised cluster analysis was used. A total of 100 surveys were gathered. Unsupervised cluster analysis was used to group individuals with similar dimensions highlighting three general genres of influencers: well-rounded, knowledge and relational. Culture is created locally by individual influencers. Cluster analysis is an effective way to identify common characteristics among members of an intensive care unit team that are noted as highly influential by their peers. To change culture, identifying and then integrating the influencers in intervention development and dissemination may create more sustainable and effective culture change. Additional studies are ongoing to test the effectiveness of utilising these influencers to disseminate patient safety interventions. This study offers an approach that can be helpful in both identifying and understanding influential team members and may be an important aspect of developing methods to change organisational culture. © 2017 John Wiley & Sons Ltd.

  2. Identifying Effective Spelling Interventions Using a Brief Experimental Analysis and Extended Analysis

    Science.gov (United States)

    McCurdy, Merilee; Clure, Lynne F.; Bleck, Amanda A.; Schmitz, Stephanie L.

    2016-01-01

    Spelling is an important skill that is crucial to effective written communication. In this study, brief experimental analysis procedures were used to examine spelling instruction strategies (e.g., whole word correction; word study strategy; positive practice; and cover, copy, and compare) for four students. In addition, an extended analysis was…

  3. Comparative analysis of Salmonella genomes identifies a metabolic network for escalating growth in the inflamed gut.

    Science.gov (United States)

    Nuccio, Sean-Paul; Bäumler, Andreas J

    2014-03-18

    The Salmonella genus comprises a group of pathogens associated with illnesses ranging from gastroenteritis to typhoid fever. We performed an in silico analysis of comparatively reannotated Salmonella genomes to identify genomic signatures indicative of disease potential. By removing numerous annotation inconsistencies and inaccuracies, the process of reannotation identified a network of 469 genes involved in central anaerobic metabolism, which was intact in genomes of gastrointestinal pathogens but degrading in genomes of extraintestinal pathogens. This large network contained pathways that enable gastrointestinal pathogens to utilize inflammation-derived nutrients as well as many of the biochemical reactions used for the enrichment and biochemical discrimination of Salmonella serovars. Thus, comparative genome analysis identifies a metabolic network that provides clues about the strategies for nutrient acquisition and utilization that are characteristic of gastrointestinal pathogens. IMPORTANCE While some Salmonella serovars cause infections that remain localized to the gut, others disseminate throughout the body. Here, we compared Salmonella genomes to identify characteristics that distinguish gastrointestinal from extraintestinal pathogens. We identified a large metabolic network that is functional in gastrointestinal pathogens but decaying in extraintestinal pathogens. While taxonomists have used traits from this network empirically for many decades for the enrichment and biochemical discrimination of Salmonella serovars, our findings suggest that it is part of a "business plan" for growth in the inflamed gastrointestinal tract. By identifying a large metabolic network characteristic of Salmonella serovars associated with gastroenteritis, our in silico analysis provides a blueprint for potential strategies to utilize inflammation-derived nutrients and edge out competing gut microbes.

  4. A parameter estimation and identifiability analysis methodology applied to a street canyon air pollution model

    DEFF Research Database (Denmark)

    Ottosen, T. B.; Ketzel, Matthias; Skov, H.

    2016-01-01

    Mathematical models are increasingly used in environmental science thus increasing the importance of uncertainty and sensitivity analyses. In the present study, an iterative parameter estimation and identifiability analysis methodology is applied to an atmospheric model – the Operational Street...... of the identifiability analysis, showed that some model parameters were significantly more sensitive than others. The application of the determined optimal parameter values was shown to successfully equilibrate the model biases among the individual streets and species. It was as well shown that the frequentist approach...

  5. Identifying Subgroups of Tinnitus Using Novel Resting State fMRI Biomarkers and Cluster Analysis

    Science.gov (United States)

    2017-10-13

    applied to the resting-state data to identify tinnitus subgroups within the patient population and pair them with specific behavioral ...and behavioral data  Specific Aim 2: Determine tinnitus subgroups using automated cluster analysis of resting state data and associate the subgroups...data analysis and clustering method previously developed to apply to current tinnitus data set o Percentage of completion at end of Year 2 (24 months

  6. Analysis of promoter regions of co-expressed genes identified by microarray analysis

    Directory of Open Access Journals (Sweden)

    Höglund Mattias

    2006-08-01

    Full Text Available Abstract Background The use of global gene expression profiling to identify sets of genes with similar expression patterns is rapidly becoming a widespread approach for understanding biological processes. A logical and systematic approach to study co-expressed genes is to analyze their promoter sequences to identify transcription factors that may be involved in establishing specific profiles and that may be experimentally investigated. Results We introduce promoter clustering i.e. grouping of promoters with respect to their high scoring motif content, and show that this approach greatly enhances the identification of common and significant transcription factor binding sites (TFBS in co-expressed genes. We apply this method to two different dataset, one consisting of micro array data from 108 leukemias (AMLs and a second from a time series experiment, and show that biologically relevant promoter patterns may be obtained using phylogenetic foot-printing methodology. In addition, we also found that 15% of the analyzed promoter regions contained transcription factors start sites for additional genes transcribed in the opposite direction. Conclusion Promoter clustering based on global promoter features greatly improve the identification of shared TFBS in co-expressed genes. We believe that the outlined approach may be a useful first step to identify transcription factors that contribute to specific features of gene expression profiles.

  7. Sparse canonical correlation analysis for identifying, connecting and completing gene-expression networks

    Directory of Open Access Journals (Sweden)

    Zwinderman Aeilko H

    2009-09-01

    Full Text Available Abstract Background We generalized penalized canonical correlation analysis for analyzing microarray gene-expression measurements for checking completeness of known metabolic pathways and identifying candidate genes for incorporation in the pathway. We used Wold's method for calculation of the canonical variates, and we applied ridge penalization to the regression of pathway genes on canonical variates of the non-pathway genes, and the elastic net to the regression of non-pathway genes on the canonical variates of the pathway genes. Results We performed a small simulation to illustrate the model's capability to identify new candidate genes to incorporate in the pathway: in our simulations it appeared that a gene was correctly identified if the correlation with the pathway genes was 0.3 or more. We applied the methods to a gene-expression microarray data set of 12, 209 genes measured in 45 patients with glioblastoma, and we considered genes to incorporate in the glioma-pathway: we identified more than 25 genes that correlated > 0.9 with canonical variates of the pathway genes. Conclusion We concluded that penalized canonical correlation analysis is a powerful tool to identify candidate genes in pathway analysis.

  8. Systematic In Vivo RNAi Analysis Identifies IAPs as NEDD8-E3 Ligases

    DEFF Research Database (Denmark)

    Broemer, Meike; Tenev, Tencho; Rigbolt, Kristoffer T G

    2010-01-01

    -like proteins (UBLs), and deconjugating enzymes that remove the Ub or UBL adduct. Systematic in vivo RNAi analysis identified three NEDD8-specific isopeptidases that, when knocked down, suppress apoptosis. Consistent with the notion that attachment of NEDD8 prevents cell death, genetic ablation of deneddylase 1...

  9. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

    NARCIS (Netherlands)

    Voight, Benjamin F.; Scott, Laura J.; Steinthorsdottir, Valgerdur; Morris, Andrew P.; Dina, Christian; Welch, Ryan P.; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii S.; Thorleifsson, Gudmar; McCulloch, Laura J.; Ferreira, Teresa; Grallert, Harald; Amin, Najaf; Wu, Guanming; Willer, Cristen J.; Raychaudhuri, Soumya; McCarroll, Steve A.; Langenberg, Claudia; Hofmann, Oliver M.; Dupuis, Josee; Qi, Lu; Segre, Ayellet V.; van Hoek, Mandy; Navarro, Pau; Ardlie, Kristin; Balkau, Beverley; Benediktsson, Rafn; Bennett, Amanda J.; Blagieva, Roza; Boerwinkle, Eric; Bonnycastle, Lori L.; Bostrom, Kristina Bengtsson; Bravenboer, Bert; Bumpstead, Suzannah; Burtt, Noisel P.; Charpentier, Guillaume; Chines, Peter S.; Cornelis, Marilyn; Couper, David J.; Crawford, Gabe; Doney, Alex S. F.; Elliott, Katherine S.; Elliott, Amanda L.; Erdos, Michael R.; Fox, Caroline S.; Franklin, Christopher S.; Ganser, Martha; Gieger, Christian; Grarup, Niels; Green, Todd; Griffin, Simon; Groves, Christopher J.; Guiducci, Candace; Hadjadj, Samy; Hassanali, Neelam; Herder, Christian; Isomaa, Bo; Jackson, Anne U.; Johnson, Paul R. V.; Jorgensen, Torben; Kao, Wen H. L.; Klopp, Norman; Kong, Augustine; Kraft, Peter; Kuusisto, Johanna; Lauritzen, Torsten; Li, Man; Lieverse, Aloysius; Lindgren, Cecilia M.; Lyssenko, Valeriya; Marre, Michel; Meitinger, Thomas; Midthjell, Kristian; Morken, Mario A.; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R.; Payne, Felicity; Perry, John R. B.; Petersen, Ann-Kristin; Platou, Carl; Proenca, Christine; Prokopenko, Inga; Rathmann, Wolfgang; Rayner, N. William; Robertson, Neil R.; Rocheleau, Ghislain; Roden, Michael; Sampson, Michael J.; Saxena, Richa; Shields, Beverley M.; Shrader, Peter; Sigurdsson, Gunnar; Sparso, Thomas; Strassburger, Klaus; Stringham, Heather M.; Sun, Qi; Swift, Amy J.; Thorand, Barbara; Tichet, Jean; Tuomi, Tiinamaija; van Dam, Rob M.; van Haeften, Timon W.; van Herpt, Thijs; van Vliet-Ostaptchouk, Jana V.; Walters, G. Bragi; Weedon, Michael N.; Wijmenga, Cisca; Witteman, Jacqueline; Bergman, Richard N.; Cauchi, Stephane; Collins, Francis S.; Gloyn, Anna L.; Gyllensten, Ulf; Hansen, Torben; Hide, Winston A.; Hitman, Graham A.; Hofman, Albert; Hunter, David J.; Hveem, Kristian; Laakso, Markku; Mohlke, Karen L.; Morris, Andrew D.; Palmer, Colin N. A.; Pramstaller, Peter P.; Rudan, Igor; Sijbrands, Eric; Stein, Lincoln D.; Tuomilehto, Jaakko; Uitterlinden, Andre; Walker, Mark; Wareham, Nicholas J.; Watanabe, Richard M.; Abecasis, Goncalo R.; Boehm, Bernhard O.; Campbell, Harry; Daly, Mark J.; Hattersley, Andrew T.; Hu, Frank B.; Meigs, James B.; Pankow, James S.; Pedersen, Oluf; Wichmann, H-Erich; Barroso, Ines; Florez, Jose C.; Frayling, Timothy M.; Groop, Leif; Sladek, Rob; Thorsteinsdottir, Unnur; Wilson, James F.; Illig, Thomas; Froguel, Philippe; van Duijn, Cornelia M.; Stefansson, Kari; Altshuler, David; Boehnke, Michael; McCarthy, Mark I.

    By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined

  10. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

    NARCIS (Netherlands)

    B.F. Voight (Benjamin); L.J. Scott (Laura); V. Steinthorsdottir (Valgerdur); A.D. Morris (Andrew); C. Dina (Christian); R.P. Welch (Ryan); E. Zeggini (Eleftheria); C. Huth (Cornelia); Y.S. Aulchenko (Yurii); G. Thorleifsson (Gudmar); L.J. McCulloch (Laura); T. Ferreira (Teresa); H. Grallert (Harald); N. Amin (Najaf); G. Wu (Guanming); C.J. Willer (Cristen); S. Raychaudhuri (Soumya); S.A. McCarroll (Steven); C. Langenberg (Claudia); O.M. Hofmann (Oliver); J. Dupuis (Josée); L. Qi (Lu); A.V. Segrè (Ayellet); M. van Hoek (Mandy); P. Navarro (Pau); K.G. Ardlie (Kristin); B. Balkau (Beverley); R. Benediktsson (Rafn); A.J. Bennett (Amanda); R. Blagieva (Roza); E.A. Boerwinkle (Eric); L.L. Bonnycastle (Lori); K.B. Boström (Kristina Bengtsson); B. Bravenboer (Bert); S. Bumpstead (Suzannah); N.P. Burtt (Noël); G. Charpentier (Guillaume); P.S. Chines (Peter); M. Cornelis (Marilyn); D.J. Couper (David); G. Crawford (Gabe); A.S.F. Doney (Alex); K.S. Elliott (Katherine); M.R. Erdos (Michael); C.S. Fox (Caroline); C.S. Franklin (Christopher); M. Ganser (Martha); C. Gieger (Christian); N. Grarup (Niels); T. Green (Todd); S. Griffin (Simon); C.J. Groves (Christopher); C. Guiducci (Candace); S. Hadjadj (Samy); N. Hassanali (Neelam); C. Herder (Christian); B. Isomaa (Bo); A.U. Jackson (Anne); P.R.V. Johnson (Paul); T. Jørgensen (Torben); W.H.L. Kao (Wen); N. Klopp (Norman); A. Kong (Augustine); P. Kraft (Peter); J. Kuusisto (Johanna); T. Lauritzen (Torsten); M. Li (Man); A. Lieverse (Aloysius); C.M. Lindgren (Cecilia); V. Lyssenko (Valeriya); M. Marre (Michel); T. Meitinger (Thomas); K. Midthjell (Kristian); M.A. Morken (Mario); N. Narisu (Narisu); P. Nilsson (Peter); K.R. Owen (Katharine); F. Payne (Felicity); J.R.B. Perry (John); A.K. Petersen; C. Platou (Carl); C. Proença (Christine); I. Prokopenko (Inga); W. Rathmann (Wolfgang); N.W. Rayner (Nigel William); N.R. Robertson (Neil); G. Rocheleau (Ghislain); M. Roden (Michael); M.J. Sampson (Michael); R. Saxena (Richa); B.M. Shields (Beverley); P. Shrader (Peter); G. Sigurdsson (Gunnar); T. Sparsø (Thomas); K. Strassburger (Klaus); H.M. Stringham (Heather); Q. Sun (Qi); A.J. Swift (Amy); B. Thorand (Barbara); J. Tichet (Jean); T. Tuomi (Tiinamaija); R.M. van Dam (Rob); T.W. van Haeften (Timon); T.W. van Herpt (Thijs); J.V. van Vliet-Ostaptchouk (Jana); G.B. Walters (Bragi); M.N. Weedon (Michael); C. Wijmenga (Cisca); J.C.M. Witteman (Jacqueline); R.N. Bergman (Richard); S. Cauchi (Stephane); F.S. Collins (Francis); A.L. Gloyn (Anna); U. Gyllensten (Ulf); T. Hansen (Torben); W.A. Hide (Winston); G.A. Hitman (Graham); A. Hofman (Albert); D. Hunter (David); K. Hveem (Kristian); M. Laakso (Markku); K.L. Mohlke (Karen); C.N.A. Palmer (Colin); P.P. Pramstaller (Peter Paul); I. Rudan (Igor); E.J.G. Sijbrands (Eric); L.D. Stein (Lincoln); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); M. Walker (Mark); N.J. Wareham (Nick); G.R. Abecasis (Gonçalo); B.O. Boehm (Bernhard); H. Campbell (Harry); M.J. Daly (Mark); A.T. Hattersley (Andrew); F.B. Hu (Frank); J.B. Meigs (James); J.S. Pankow (James); O. Pedersen (Oluf); H.E. Wichmann (Erich); I. Barroso (Inês); J.C. Florez (Jose); T.M. Frayling (Timothy); L. Groop (Leif); R. Sladek (Rob); U. Thorsteinsdottir (Unnur); J.F. Wilson (James); T. Illig (Thomas); P. Froguel (Philippe); P. Tikka-Kleemola (Päivi); J-A. Zwart (John-Anker); D. Altshuler (David); M. Boehnke (Michael); M.I. McCarthy (Mark); R.M. Watanabe (Richard)

    2010-01-01

    textabstractBy combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals

  11. Identifying Skill Requirements for GIS Positions: A Content Analysis of Job Advertisements

    Science.gov (United States)

    Hong, Jung Eun

    2016-01-01

    This study identifies the skill requirements for geographic information system (GIS) positions, including GIS analysts, programmers/developers/engineers, specialists, and technicians, through a content analysis of 946 GIS job advertisements from 2007-2014. The results indicated that GIS job applicants need to possess high levels of GIS analysis…

  12. Exome-wide rare variant analysis identifies TUBA4A mutations associated with familial ALS

    NARCIS (Netherlands)

    Smith, Bradley N.; Ticozzi, Nicola; Fallini, Claudia; Gkazi, Athina Soragia; Topp, Simon; Kenna, Kevin P.; Scotter, Emma L.; Kost, Jason; Keagle, Pamela; Miller, Jack W.; Calini, Daniela; Vance, Caroline; Danielson, Eric W.; Troakes, Claire; Tiloca, Cinzia; Al-Sarraj, Safa; Lewis, Elizabeth A.; King, Andrew; Colombrita, Claudia; Pensato, Viviana; Castellotti, Barbara; de Belleroche, Jacqueline; Baas, Frank; ten Asbroek, Anneloor L. M. A.; Sapp, Peter C.; McKenna-Yasek, Diane; McLaughlin, Russell L.; Polak, Meraida; Asress, Seneshaw; Esteban-Pérez, Jesús; Muñoz-Blanco, José Luis; Simpson, Michael; van Rheenen, Wouter; Diekstra, Frank P.; Lauria, Giuseppe; Duga, Stefano; Corti, Stefania; Cereda, Cristina; Corrado, Lucia; Sorarù, Gianni; Morrison, Karen E.; Williams, Kelly L.; Nicholson, Garth A.; Blair, Ian P.; Dion, Patrick A.; Leblond, Claire S.; Rouleau, Guy A.; Hardiman, Orla; Veldink, Jan H.; van den Berg, Leonard H.; Al-Chalabi, Ammar; Pall, Hardev; Shaw, Pamela J.; Turner, Martin R.; Talbot, Kevin; Taroni, Franco; García-Redondo, Alberto; Wu, Zheyang; Glass, Jonathan D.; Gellera, Cinzia; Ratti, Antonia; Brown, Robert H.; Silani, Vincenzo; Shaw, Christopher E.; Landers, John E.; D'alfonso, Sandra; Mazzini, Letizia; Comi, Giacomo P.; del Bo, Roberto; Ceroni, Mauro; Gagliardi, Stella; Querin, Giorgia; Bertolin, Cinzia

    2014-01-01

    Exome sequencing is an effective strategy for identifying human disease genes. However, this methodology is difficult in late-onset diseases where limited availability of DNA from informative family members prohibits comprehensive segregation analysis. To overcome this limitation, we performed an

  13. Social Network Analysis: A Simple but Powerful Tool for Identifying Teacher Leaders

    Science.gov (United States)

    Smith, P. Sean; Trygstad, Peggy J.; Hayes, Meredith L.

    2018-01-01

    Instructional teacher leadership is central to a vision of distributed leadership. However, identifying instructional teacher leaders can be a daunting task, particularly for administrators who find themselves either newly appointed or faced with high staff turnover. This article describes the use of social network analysis (SNA), a simple but…

  14. Genome-based exome sequencing analysis identifies GYG1, DIS3L ...

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 96; Issue 6. Genome-based exome sequencing analysis identifies GYG1, DIS3L and DDRGK1 are associated with myocardial infarction in Koreans. JI-YOUNG LEE SANGHOON MOON YUN KYOUNG KIM SANG-HAK LEE BOK-SOO LEE MIN-YOUNG PARK JEONG EUY PARK ...

  15. Are Young Dual Language Learners Homogeneous? Identifying Subgroups Using Latent Class Analysis

    Science.gov (United States)

    Kim, Do-Hong; Lambert, Richard G.; Burts, Diane C.

    2018-01-01

    Although dual language learners (DLLs) are linguistically, culturally, and socially diverse, researchers usually study them in aggregate and compare them to non-DLLs. The authors' purpose was to identify subgroups of preschool DLLs using latent class analysis. There were 7,361 DLLs and 69,457 non-DLLs. Results revealed three distinct classes.…

  16. Using Latent Class Analysis to Identify Academic and Behavioral Risk Status in Elementary Students

    Science.gov (United States)

    King, Kathleen R.; Lembke, Erica S.; Reinke, Wendy M.

    2016-01-01

    Identifying classes of children on the basis of academic and behavior risk may have important implications for the allocation of intervention resources within Response to Intervention (RTI) and Multi-Tiered System of Support (MTSS) models. Latent class analysis (LCA) was conducted with a sample of 517 third grade students. Fall screening scores in…

  17. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution

    NARCIS (Netherlands)

    C.M. Lindgren (Cecilia); I.M. Heid (Iris); J.C. Randall (Joshua); C. Lamina (Claudia); V. Steinthorsdottir (Valgerdur); L. Qi (Lu); E.K. Speliotes (Elizabeth); G. Thorleifsson (Gudmar); C.J. Willer (Cristen); B.M. Herrera (Blanca); A.U. Jackson (Anne); N. Lim (Noha); P. Scheet (Paul); N. Soranzo (Nicole); N. Amin (Najaf); Y.S. Aulchenko (Yurii); J.C. Chambers (John); A. Drong (Alexander); J. Luan; H.N. Lyon (Helen); F. Rivadeneira Ramirez (Fernando); S. Sanna (Serena); N.J. Timpson (Nicholas); M.C. Zillikens (Carola); H.Z. Jing; P. Almgren (Peter); S. Bandinelli (Stefania); A.J. Bennett (Amanda); R.N. Bergman (Richard); L.L. Bonnycastle (Lori); S. Bumpstead (Suzannah); S.J. Chanock (Stephen); L. Cherkas (Lynn); P.S. Chines (Peter); L. Coin (Lachlan); C. Cooper (Charles); G. Crawford (Gabe); A. Doering (Angela); A. Dominiczak (Anna); A.S.F. Doney (Alex); S. Ebrahim (Shanil); P. Elliott (Paul); M.R. Erdos (Michael); K. Estrada Gil (Karol); L. Ferrucci (Luigi); G. Fischer (Guido); N.G. Forouhi (Nita); C. Gieger (Christian); H. Grallert (Harald); C.J. Groves (Christopher); S.M. Grundy (Scott); C. Guiducci (Candace); D. Hadley (David); A. Hamsten (Anders); A.S. Havulinna (Aki); A. Hofman (Albert); R. Holle (Rolf); J.W. Holloway (John); T. Illig (Thomas); B. Isomaa (Bo); L.C. Jacobs (Leonie); K. Jameson (Karen); P. Jousilahti (Pekka); F. Karpe (Fredrik); J. Kuusisto (Johanna); J. Laitinen (Jaana); G.M. Lathrop (Mark); D.A. Lawlor (Debbie); M. Mangino (Massimo); W.L. McArdle (Wendy); T. Meitinger (Thomas); M.A. Morken (Mario); A.P. Morris (Andrew); P. Munroe (Patricia); N. Narisu (Narisu); A. Nordström (Anna); B.A. Oostra (Ben); C.N.A. Palmer (Colin); F. Payne (Felicity); J. Peden (John); I. Prokopenko (Inga); F. Renström (Frida); A. Ruokonen (Aimo); V. Salomaa (Veikko); M.S. Sandhu (Manjinder); L.J. Scott (Laura); A. Scuteri (Angelo); K. Silander (Kaisa); K. Song (Kijoung); X. Yuan (Xin); H.M. Stringham (Heather); A.J. Swift (Amy); T. Tuomi (Tiinamaija); M. Uda (Manuela); P. Vollenweider (Peter); G. Waeber (Gérard); C. Wallace (Chris); G.B. Walters (Bragi); M.N. Weedon (Michael); J.C.M. Witteman (Jacqueline); C. Zhang (Cuilin); M. Caulfield (Mark); F.S. Collins (Francis); G.D. Smith; I.N.M. Day (Ian); P.W. Franks (Paul); A.T. Hattersley (Andrew); F.B. Hu (Frank); M.-R. Jarvelin (Marjo-Riitta); A. Kong (Augustine); J.S. Kooner (Jaspal); M. Laakso (Markku); E. Lakatta (Edward); V. Mooser (Vincent); L. Peltonen (Leena Johanna); N.J. Samani (Nilesh); T.D. Spector (Timothy); D.P. Strachan (David); T. Tanaka (Toshiko); J. Tuomilehto (Jaakko); A.G. Uitterlinden (André); P. Tikka-Kleemola (Päivi); N.J. Wareham (Nick); H. Watkins (Hugh); D. Waterworth (Dawn); M. Boehnke (Michael); P. Deloukas (Panagiotis); L. Groop (Leif); D.J. Hunter (David); U. Thorsteinsdottir (Unnur); D. Schlessinger (David); H.E. Wichmann (Erich); T.M. Frayling (Timothy); G.R. Abecasis (Gonçalo); J.N. Hirschhorn (Joel); R.J.F. Loos (Ruth); J-A. Zwart (John-Anker); K.L. Mohlke (Karen); I. Barroso (Inês); M.I. McCarthy (Mark)

    2009-01-01

    textabstractTo identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist-hip ratio (WHR). We selected 26 SNPs for follow-up, for which the

  18. AcuI identifies water buffalo CSN3 genotypes by RFLP analysis

    Indian Academy of Sciences (India)

    Home; Journals; Journal of Genetics; Volume 93; Online resources. AcuI identifies water buffalo CSN3 genotypes by RFLP analysis. Soheir M. El Nahas Ahlam A. Abou Mossallam. Volume 93 Online resources 2014 pp e94-e96. Fulltext. Click here to view fulltext PDF. Permanent link:

  19. Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

    DEFF Research Database (Denmark)

    Boomsma, Wouter Krogh; Nielsen, Sofie Vincents; Lindorff-Larsen, Kresten

    2016-01-01

    conduct a bioinformatics analysis to examine >600 human and S. cerevisiae E3 ligases to identify enzymes that are similar to San1 in terms of function and/or mechanism of substrate recognition. An initial sequence-based database search was found to detect candidates primarily based on the homology...

  20. Genetic analysis to identify good combiners for ToLCV resistance ...

    Indian Academy of Sciences (India)

    2014-11-10

    Nov 10, 2014 ... RESEARCH ARTICLE. Genetic analysis to identify good combiners for ToLCV resistance and yield components in tomato using interspecific hybridization. RAMESH K. SINGH1,2,3, N. RAI1∗, MAJOR SINGH1, S. N. SINGH2 and K. SRIVASTAVA4. 1Crop Improvement Division, Indian Institute of Vegetable ...

  1. Identifying Subgroups of Tinnitus Using Novel Resting State fMRI Biomarkers and Cluster Analysis

    Science.gov (United States)

    2016-10-01

    project activities, for the purpose of enhancing public understanding and increasing interest in learning and careers in science, technology, and the... Unsupervised hierarchical clustering of resting state functional connectivity data to identify patients with mild tinnitus. Poster session presented...including drafting of IRB behavioral and scanning protocols, advising on recruiting and initial data collection. She also supervised analysis of data and

  2. Large-scale association analysis identifies new risk loci for coronary artery disease

    NARCIS (Netherlands)

    Deloukas, Panos; Kanoni, Stavroula; Willenborg, Christina; Farrall, Martin; Assimes, Themistocles L.; Thompson, John R.; Ingelsson, Erik; Saleheen, Danish; Erdmann, Jeanette; Goldstein, Benjamin A.; Stirrups, Kathleen; König, Inke R.; Cazier, Jean-Baptiste; Johansson, Asa; Hall, Alistair S.; Lee, Jong-Young; Willer, Cristen J.; Chambers, John C.; Esko, Tõnu; Folkersen, Lasse; Goel, Anuj; Grundberg, Elin; Havulinna, Aki S.; Ho, Weang K.; Hopewell, Jemma C.; Eriksson, Niclas; Kleber, Marcus E.; Kristiansson, Kati; Lundmark, Per; Lyytikäinen, Leo-Pekka; Rafelt, Suzanne; Shungin, Dmitry; Strawbridge, Rona J.; Thorleifsson, Gudmar; Tikkanen, Emmi; van Zuydam, Natalie; Voight, Benjamin F.; Waite, Lindsay L.; Zhang, Weihua; Ziegler, Andreas; Absher, Devin; Altshuler, David; Balmforth, Anthony J.; Barroso, Inês; Braund, Peter S.; Burgdorf, Christof; Claudi-Boehm, Simone; Cox, David; Dimitriou, Maria; Do, Ron; Doney, Alex S. F.; El Mokhtari, NourEddine; Eriksson, Per; Fischer, Krista; Fontanillas, Pierre; Franco-Cereceda, Anders; Gigante, Bruna; Groop, Leif; Gustafsson, Stefan; Hager, Jörg; Hallmans, Göran; Han, Bok-Ghee; Hunt, Sarah E.; Kang, Hyun M.; Illig, Thomas; Kessler, Thorsten; Knowles, Joshua W.; Kolovou, Genovefa; Kuusisto, Johanna; Langenberg, Claudia; Langford, Cordelia; Leander, Karin; Lokki, Marja-Liisa; Lundmark, Anders; McCarthy, Mark I.; Meisinger, Christa; Melander, Olle; Mihailov, Evelin; Maouche, Seraya; Morris, Andrew D.; Müller-Nurasyid, Martina; Nikus, Kjell; Peden, John F.; Rayner, N. William; Rasheed, Asif; Rosinger, Silke; Rubin, Diana; Rumpf, Moritz P.; Schäfer, Arne; Sivananthan, Mohan; Song, Ci; Stewart, Alexandre F. R.; Tan, Sian-Tsung; Thorgeirsson, Gudmundur; van der Schoot, C. Ellen; Wagner, Peter J.; Wells, George A.; Wild, Philipp S.; Yang, Tsun-Po; Amouyel, Philippe; Arveiler, Dominique; Basart, Hanneke; Boehnke, Michael; Boerwinkle, Eric; Brambilla, Paolo; Cambien, Francois; Cupples, Adrienne L.; de Faire, Ulf; Dehghan, Abbas; Diemert, Patrick; Epstein, Stephen E.; Evans, Alun; Ferrario, Marco M.; Ferrières, Jean; Gauguier, Dominique; Go, Alan S.; Goodall, Alison H.; Gudnason, Villi; Hazen, Stanley L.; Holm, Hilma; Iribarren, Carlos; Jang, Yangsoo; Kähönen, Mika; Kee, Frank; Kim, Hyo-Soo; Klopp, Norman; Koenig, Wolfgang; Kratzer, Wolfgang; Kuulasmaa, Kari; Laakso, Markku; Laaksonen, Reijo; Lee, Ji-Young; Lind, Lars; Ouwehand, Willem H.; Parish, Sarah; Park, Jeong E.; Pedersen, Nancy L.; Peters, Annette; Quertermous, Thomas; Rader, Daniel J.; Salomaa, Veikko; Schadt, Eric; Shah, Svati H.; Sinisalo, Juha; Stark, Klaus; Stefansson, Kari; Trégouët, David-Alexandre; Virtamo, Jarmo; Wallentin, Lars; Wareham, Nicholas; Zimmermann, Martina E.; Nieminen, Markku S.; Hengstenberg, Christian; Sandhu, Manjinder S.; Pastinen, Tomi; Syvänen, Ann-Christine; Hovingh, G. Kees; Dedoussis, George; Franks, Paul W.; Lehtimäki, Terho; Metspalu, Andres; Zalloua, Pierre A.; Siegbahn, Agneta; Schreiber, Stefan; Ripatti, Samuli; Blankenberg, Stefan S.; Perola, Markus; Clarke, Robert; Boehm, Bernhard O.; O'Donnell, Christopher; Reilly, Muredach P.; März, Winfried; Collins, Rory; Kathiresan, Sekar; Hamsten, Anders; Kooner, Jaspal S.; Thorsteinsdottir, Unnur; Danesh, John; Palmer, Colin N. A.; Roberts, Robert; Watkins, Hugh; Schunkert, Heribert; Samani, Nilesh J.

    2013-01-01

    Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2)

  3. Identifying sustainability issues using participatory SWOT analysis - A case study of egg production in the Netherlands

    NARCIS (Netherlands)

    Mollenhorst, H.; Boer, de I.J.M.

    2004-01-01

    The aim of this paper was to demonstrate how participatory strengths, weaknesses, opportunities and threats (SWOT) analysis can be used to identify relevant economic, ecological and societal (EES) issues for the assessment of sustainable development. This is illustrated by the case of egg production

  4. Identifying the "Right Stuff": An Exploration-Focused Astronaut Job Analysis

    Science.gov (United States)

    Barrett, J. D.; Holland, A. W.; Vessey, W. B.

    2015-01-01

    Industrial and organizational (I/O) psychologists play a key role in NASA astronaut candidate selection through the identification of the competencies necessary to successfully engage in the astronaut job. A set of psychosocial competencies, developed by I/O psychologists during a prior job analysis conducted in 1996 and updated in 2003, were identified as necessary for individuals working and living in the space shuttle and on the International Space Station (ISS). This set of competencies applied to the space shuttle and applies to current ISS missions, but may not apply to longer-duration or long-distance exploration missions. With the 2015 launch of the first 12- month ISS mission and the shift in the 2020s to missions beyond low earth orbit, the type of missions that astronauts will conduct and the environment in which they do their work will change dramatically, leading to new challenges for these crews. To support future astronaut selection, training, and research, I/O psychologists in NASA's Behavioral Health and Performance (BHP) Operations and Research groups engaged in a joint effort to conduct an updated analysis of the astronaut job for current and future operations. This project will result in the identification of behavioral competencies critical to performing the astronaut job, along with relative weights for each of the identified competencies, through the application of job analysis techniques. While this job analysis is being conducted according to job analysis best practices, the project poses a number of novel challenges. These challenges include the need to identify competencies for multiple mission types simultaneously, to evaluate jobs that have no incumbents as they have never before been conducted, and working with a very limited population of subject matter experts. Given these challenges, under the guidance of job analysis experts, we used the following methods to conduct the job analysis and identify the key competencies for current and

  5. Potential ligand-binding residues in rat olfactory receptors identified by correlated mutation analysis

    Science.gov (United States)

    Singer, M. S.; Oliveira, L.; Vriend, G.; Shepherd, G. M.

    1995-01-01

    A family of G-protein-coupled receptors is believed to mediate the recognition of odor molecules. In order to identify potential ligand-binding residues, we have applied correlated mutation analysis to receptor sequences from the rat. This method identifies pairs of sequence positions where residues remain conserved or mutate in tandem, thereby suggesting structural or functional importance. The analysis supported molecular modeling studies in suggesting several residues in positions that were consistent with ligand-binding function. Two of these positions, dominated by histidine residues, may play important roles in ligand binding and could confer broad specificity to mammalian odor receptors. The presence of positive (overdominant) selection at some of the identified positions provides additional evidence for roles in ligand binding. Higher-order groups of correlated residues were also observed. Each group may interact with an individual ligand determinant, and combinations of these groups may provide a multi-dimensional mechanism for receptor diversity.

  6. Gene expression meta-analysis identifies metastatic pathways and transcription factors in breast cancer

    International Nuclear Information System (INIS)

    Thomassen, Mads; Tan, Qihua; Kruse, Torben A

    2008-01-01

    Metastasis is believed to progress in several steps including different pathways but the determination and understanding of these mechanisms is still fragmentary. Microarray analysis of gene expression patterns in breast tumors has been used to predict outcome in recent studies. Besides classification of outcome, these global expression patterns may reflect biological mechanisms involved in metastasis of breast cancer. Our purpose has been to investigate pathways and transcription factors involved in metastasis by use of gene expression data sets. We have analyzed 8 publicly available gene expression data sets. A global approach, 'gene set enrichment analysis' as well as an approach focusing on a subset of significantly differently regulated genes, GenMAPP, has been applied to rank pathway gene sets according to differential regulation in metastasizing tumors compared to non-metastasizing tumors. Meta-analysis has been used to determine overrepresentation of pathways and transcription factors targets, concordant deregulated in metastasizing breast tumors, in several data sets. The major findings are up-regulation of cell cycle pathways and a metabolic shift towards glucose metabolism reflected in several pathways in metastasizing tumors. Growth factor pathways seem to play dual roles; EGF and PDGF pathways are decreased, while VEGF and sex-hormone pathways are increased in tumors that metastasize. Furthermore, migration, proteasome, immune system, angiogenesis, DNA repair and several signal transduction pathways are associated to metastasis. Finally several transcription factors e.g. E2F, NFY, and YY1 are identified as being involved in metastasis. By pathway meta-analysis many biological mechanisms beyond major characteristics such as proliferation are identified. Transcription factor analysis identifies a number of key factors that support central pathways. Several previously proposed treatment targets are identified and several new pathways that may

  7. Identifying and Characterizing Discrepancies Between Test and Analysis Results of Compression-Loaded Panels

    Science.gov (United States)

    Thornburgh, Robert P.; Hilburger, Mark W.

    2005-01-01

    Results from a study to identify and characterize discrepancies between validation tests and high-fidelity analyses of compression-loaded panels are presented. First, potential sources of the discrepancies in both the experimental method and corresponding high-fidelity analysis models were identified. Then, a series of laboratory tests and numerical simulations were conducted to quantify the discrepancies and develop test and analysis methods to account for the discrepancies. The results indicate that the discrepancies between the validation tests and high-fidelity analyses can be attributed to imperfections in the test fixture and specimen geometry; test-fixture-induced changes in specimen geometry; and test-fixture-induced friction on the loaded edges of the test specimen. The results also show that accurate predictions of the panel response can be obtained when these specimen imperfections and edge conditions are accounted for in the analysis. The errors in the tests and analyses, and the methods used to characterize these errors are presented.

  8. A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder

    Directory of Open Access Journals (Sweden)

    David G Ashbrook

    2015-07-01

    Full Text Available Bipolar disorder (BD is a significant neuropsychiatric disorder with a lifetime prevalence of ~1%. To identify genetic variants underlying BD genome-wide association studies (GWAS have been carried out. While many variants of small effect associated with BD have been identified few have yet been confirmed, partly because of the low power of GWAS due to multiple comparisons being made. Complementary mapping studies using murine models have identified genetic variants for behavioral traits linked to BD, often with high power, but these identified regions often contain too many genes for clear identification of candidate genes. In the current study we have aligned human BD GWAS results and mouse linkage studies to help define and evaluate candidate genes linked to BD, seeking to use the power of the mouse mapping with the precision of GWAS. We use quantitative trait mapping for open field test and elevated zero maze data in the largest mammalian model system, the BXD recombinant inbred mouse population, to identify genomic regions associated with these BD-like phenotypes. We then investigate these regions in whole genome data from the Psychiatric Genomics Consortium’s bipolar disorder GWAS to identify candidate genes associated with BD. Finally we establish the biological relevance and pathways of these genes in a comprehensive systems genetics analysis.We identify four genes associated with both mouse anxiety and human BD. While TNR is a novel candidate for BD, we can confirm previously suggested associations with CMYA5, MCTP1 and RXRG. A cross-species, systems genetics analysis shows that MCTP1, RXRG and TNR coexpress with genes linked to psychiatric disorders and identify the striatum as a potential site of action. CMYA5, MCTP1, RXRG and TNR are associated with mouse anxiety and human BD. We hypothesize that MCTP1, RXRG and TNR influence intercellular signaling in the striatum.

  9. mK-Scanning Probe Microscope(mK-SPM) operating in a Cryogen-Free Dilution Refrigerator at 20mK

    Science.gov (United States)

    Dede, Munir; Karci, Ozgur; Snelling, Chris; Oral, Ahmet

    2012-02-01

    Dramatic increase in liquid helium price limits the usage of cryogenic equipment. Dry cryogen-free dilution refrigerators(DR) systems are promising platforms to run mK-Scanning Probe Microscopes(mK-SPM) systems with a number of operating modes: STM, AFM, MFM, EFM, SSRM, PFM, etc. We present the design of a mK-Scanning Probe Microscope (mK-SPM) operating in a cryogen-free DR. An Oxford Instrument cryogen-free DR(Triton DR200) with 200uW cooling power and 7mK base temperature is used for the experiments. A 1W Pulse Tube cryocooler is integrated into the DR. After wiring and attaching the microscope we achieved 20mK base temperature. Piezo driven Stick slip coarse approach mechanism is used to bring the sample in to close proximity of the sample. In these initial results we deliberately did not take any precautions to isolate the pumping lines, attached to the DR and the DR itself. The turbomolecular pump was attached directly to the top plate of the DR. We first tested our mK-SPM in Scanning Tunnelling Microscope (STM) mode as it is the most sensitive of the SPM techniques. An image, using a gold coated 6μm period calibration grating at 20mK, obtained under these rudimentary conditions.

  10. Using Latent Semantic Analysis to Identify Research Trends in OpenStreetMap

    Directory of Open Access Journals (Sweden)

    Sukhjit Singh Sehra

    2017-07-01

    Full Text Available OpenStreetMap (OSM, based on collaborative mapping, has become a subject of great interest to the academic community, resulting in a considerable body of literature produced by many researchers. In this paper, we use Latent Semantic Analysis (LSA to help identify the emerging research trends in OSM. An extensive corpus of 485 academic abstracts of papers published during the period 2007–2016 was used. Five core research areas and fifty research trends were identified in this study. In addition, potential future research directions have been provided to aid geospatial information scientists, technologists and researchers in undertaking future OSM research.

  11. Research citation analysis of nursing academics in Canada: identifying success indicators.

    Science.gov (United States)

    Hack, Thomas F; Crooks, Dauna; Plohman, James; Kepron, Emma

    2010-11-01

    This article is a report of a citation analysis of research publications by Canadian nursing academics. Citation analysis can yield objective criteria for assessing the value of published research and is becoming increasingly popular as an academic evaluation tool in universities around the world. Citation analysis is useful for examining the research performance of academic researchers and identifying leaders among them. The journal publication records of 737 nursing academics at 33 Canadian universities and schools of nursing were subject to citation analysis using the Scopus database. Three primary types of analysis were performed for each individual: number of citations for each journal publication, summative citation count of all published papers and the Scopus h-index. Preliminary citation analysis was conducted from June to July 2009, with the final analysis performed on 2 October 2009 following e-mail verification of publication lists. The top 20 nursing academics for each of five citation categories are presented: the number of career citations for all publications, number of career citations for first-authored publications, most highly cited first-authored publications, the Scopus h-index for all publications and the Scopus h-index for first-authored publications. Citation analysis metrics are useful for evaluating the research performance of academic researchers in nursing. Institutions are encouraged to protect the research time of successful and promising nursing academics, and to dedicate funds to enhance the research programmes of underperforming academic nursing groups. © 2010 The Authors. Journal of Advanced Nursing © 2010 Blackwell Publishing Ltd.

  12. Comparative analysis of methods for identifying multimorbidity patterns: a study of 'real-world' data.

    Science.gov (United States)

    Roso-Llorach, Albert; Violán, Concepción; Foguet-Boreu, Quintí; Rodriguez-Blanco, Teresa; Pons-Vigués, Mariona; Pujol-Ribera, Enriqueta; Valderas, Jose Maria

    2018-03-22

    The aim was to compare multimorbidity patterns identified with the two most commonly used methods: hierarchical cluster analysis (HCA) and exploratory factor analysis (EFA) in a large primary care database. Specific objectives were: (1) to determine whether choice of method affects the composition of these patterns and (2) to consider the potential application of each method in the clinical setting. Cross-sectional study. Diagnoses were based on the 263 corresponding blocks of the International Classification of Diseases version 10. Multimorbidity patterns were identified using HCA and EFA. Analysis was stratified by sex, and results compared for each method. Electronic health records for 408 994 patients with multimorbidity aged 45-64 years in 274 primary health care teams from 2010 in Catalonia, Spain. HCA identified 53 clusters for women, with just 12 clusters including at least 2 diagnoses, and 15 clusters for men, all of them including at least two diagnoses. EFA showed 9 factors for women and 10 factors for men. We observed differences by sex and method of analysis, although some patterns were consistent. Three combinations of diseases were observed consistently across sex groups and across both methods: hypertension and obesity, spondylopathies and deforming dorsopathies, and dermatitis eczema and mycosis. This study showed that multimorbidity patterns vary depending on the method of analysis used (HCA vs EFA) and provided new evidence about the known limitations of attempts to compare multimorbidity patterns in real-world data studies. We found that EFA was useful in describing comorbidity relationships and HCA could be useful for in-depth study of multimorbidity. Our results suggest possible applications for each of these methods in clinical and research settings, and add information about some aspects that must be considered in standardisation of future studies: spectrum of diseases, data usage and methods of analysis. © Article author(s) (or their

  13. Patent Network Analysis and Quadratic Assignment Procedures to Identify the Convergence of Robot Technologies.

    Directory of Open Access Journals (Sweden)

    Woo Jin Lee

    Full Text Available Because of the remarkable developments in robotics in recent years, technological convergence has been active in this area. We focused on finding patterns of convergence within robot technology using network analysis of patents in both the USPTO and KIPO. To identify the variables that affect convergence, we used quadratic assignment procedures (QAP. From our analysis, we observed the patent network ecology related to convergence and found technologies that have great potential to converge with other robotics technologies. The results of our study are expected to contribute to setting up convergence based R&D policies for robotics, which can lead new innovation.

  14. Parameter estimation for multistage clonal expansion models from cancer incidence data: A practical identifiability analysis.

    Science.gov (United States)

    Brouwer, Andrew F; Meza, Rafael; Eisenberg, Marisa C

    2017-03-01

    Many cancers are understood to be the product of multiple somatic mutations or other rate-limiting events. Multistage clonal expansion (MSCE) models are a class of continuous-time Markov chain models that capture the multi-hit initiation-promotion-malignant-conversion hypothesis of carcinogenesis. These models have been used broadly to investigate the epidemiology of many cancers, assess the impact of carcinogen exposures on cancer risk, and evaluate the potential impact of cancer prevention and control strategies on cancer rates. Structural identifiability (the analysis of the maximum parametric information available for a model given perfectly measured data) of certain MSCE models has been previously investigated. However, structural identifiability is a theoretical property and does not address the limitations of real data. In this study, we use pancreatic cancer as a case study to examine the practical identifiability of the two-, three-, and four-stage clonal expansion models given age-specific cancer incidence data using a numerical profile-likelihood approach. We demonstrate that, in the case of the three- and four-stage models, several parameters that are theoretically structurally identifiable, are, in practice, unidentifiable. This result means that key parameters such as the intermediate cell mutation rates are not individually identifiable from the data and that estimation of those parameters, even if structurally identifiable, will not be stable. We also show that products of these practically unidentifiable parameters are practically identifiable, and, based on this, we propose new reparameterizations of the model hazards that resolve the parameter estimation problems. Our results highlight the importance of identifiability to the interpretation of model parameter estimates.

  15. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

    DEFF Research Database (Denmark)

    Voight, Benjamin F; Scott, Laura J; Steinthorsdottir, Valgerdur

    2010-01-01

    By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combi......By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals...

  16. A method for identifying compromised clients based on DNS traffic analysis

    DEFF Research Database (Denmark)

    Stevanovic, Matija; Pedersen, Jens Myrup; D’Alconzo, Alessandro

    2017-01-01

    based on DNS traffic analysis. The proposed method identifies suspicious agile DNS mappings, i.e., mappings characterized by fast changing domain names or/and IP addresses, often used by malicious services. The approach discovers clients that have queried domains contained within identified suspicious...... domain-to-IP mappings, thus assisting in pinpointing potentially compromised clients within the network. The proposed approach targets compromised clients in large-scale operational networks. We have evaluated the proposed approach using an extensive set of DNS traffic traces from different operational...... ISP networks. The evaluation illustrates a great potential of accurately identifying suspicious domain-to-IP mappings and potentially compromised clients. Furthermore, the achieved performance indicate that the novel detection approach is promising in view of the adoption in operational ISP networks...

  17. A Numerical Procedure for Model Identifiability Analysis Applied to Enzyme Kinetics

    DEFF Research Database (Denmark)

    Daele, Timothy, Van; Van Hoey, Stijn; Gernaey, Krist

    2015-01-01

    The proper calibration of models describing enzyme kinetics can be quite challenging. In the literature, different procedures are available to calibrate these enzymatic models in an efficient way. However, in most cases the model structure is already decided on prior to the actual calibration...... and Pronzato (1997) and which can be easily set up for any type of model. In this paper the proposed approach is applied to the forward reaction rate of the enzyme kinetics proposed by Shin and Kim(1998). Structural identifiability analysis showed that no local structural model problems were occurring......) identifiability problems. By using the presented approach it is possible to detect potential identifiability problems and avoid pointless calibration (and experimental!) effort....

  18. Clinical Characteristics of Exacerbation-Prone Adult Asthmatics Identified by Cluster Analysis.

    Science.gov (United States)

    Kim, Mi Ae; Shin, Seung Woo; Park, Jong Sook; Uh, Soo Taek; Chang, Hun Soo; Bae, Da Jeong; Cho, You Sook; Park, Hae Sim; Yoon, Ho Joo; Choi, Byoung Whui; Kim, Yong Hoon; Park, Choon Sik

    2017-11-01

    Asthma is a heterogeneous disease characterized by various types of airway inflammation and obstruction. Therefore, it is classified into several subphenotypes, such as early-onset atopic, obese non-eosinophilic, benign, and eosinophilic asthma, using cluster analysis. A number of asthmatics frequently experience exacerbation over a long-term follow-up period, but the exacerbation-prone subphenotype has rarely been evaluated by cluster analysis. This prompted us to identify clusters reflecting asthma exacerbation. A uniform cluster analysis method was applied to 259 adult asthmatics who were regularly followed-up for over 1 year using 12 variables, selected on the basis of their contribution to asthma phenotypes. After clustering, clinical profiles and exacerbation rates during follow-up were compared among the clusters. Four subphenotypes were identified: cluster 1 was comprised of patients with early-onset atopic asthma with preserved lung function, cluster 2 late-onset non-atopic asthma with impaired lung function, cluster 3 early-onset atopic asthma with severely impaired lung function, and cluster 4 late-onset non-atopic asthma with well-preserved lung function. The patients in clusters 2 and 3 were identified as exacerbation-prone asthmatics, showing a higher risk of asthma exacerbation. Two different phenotypes of exacerbation-prone asthma were identified among Korean asthmatics using cluster analysis; both were characterized by impaired lung function, but the age at asthma onset and atopic status were different between the two. Copyright © 2017 The Korean Academy of Asthma, Allergy and Clinical Immunology · The Korean Academy of Pediatric Allergy and Respiratory Disease

  19. RUSSIAN PATENT LANDSCAPE, CREATED BY THE RESIDENTS OF THE COUNTRY: ANALYSIS OF THE IDENTIFIED ISSUES

    OpenAIRE

    N. G. Kurakova; L. A. Tsvetkova; V. G. Zinov

    2016-01-01

    It is suggested to reach the goal for channeling limited funds into the most productive research groups inRussiaby identifying so –called leading organisations among the scientific centres. As one of the criteria for selecting organisations with potential for creating the technological breakthrough on global markets will be an indicator of their patent activity. There are presented results of patent analysis, allowing to form a rating of owners of most extensive portfolios of Russian patents,...

  20. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

    OpenAIRE

    Vries, Paul; Chasman, Daniel; Sabater-Lleal, Maria; Chen, Ming-Huei; Huffman, Jennifer E.; Steri, Maristella; Tang, Weihong; Teumer, Alexander; Marioni, Riccardo; Grossmann, Vera; Hottenga, Jouke Jan; Trompet, Stella; Müller-Nurasyid, Martina; Zhao, Jing Hua; Brody, Jennifer

    2016-01-01

    textabstractGenome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels.We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ~120 000 participants of European ancestry (95 806 participant...

  1. Hot spot analysis applied to identify ecosystem services potential in Lithuania

    Science.gov (United States)

    Pereira, Paulo; Depellegrin, Daniel; Misiune, Ieva

    2016-04-01

    Hot spot analysis are very useful to identify areas with similar characteristics. This is important for a sustainable use of the territory, since we can identify areas that need to be protected, or restored. This is a great advantage in terms of land use planning and management, since we can allocate resources, reduce the economical costs and do a better intervention in the landscape. Ecosystem services (ES) are different according land use. Since landscape is very heterogeneous, it is of major importance understand their spatial pattern and where are located the areas that provide better ES and the others that provide less services. The objective of this work is to use hot-spot analysis to identify areas with the most valuable ES in Lithuania. CORINE land-cover (CLC) of 2006 was used as the main spatial information. This classification uses a grid of 100 m resolution and extracted a total of 31 land use types. ES ranking was carried out based on expert knowledge. They were asked to evaluate the ES potential of each different CLC from 0 (no potential) to 5 (very high potential). Hot spot analysis were evaluated using the Getis-ord test, which identifies cluster analysis available in ArcGIS toolbox. This tool identifies areas with significantly high low values and significant high values at a p level of 0.05. In this work we used hot spot analysis to assess the distribution of providing, regulating cultural and total (sum of the previous 3) ES. The Z value calculated from Getis-ord was used to statistical analysis to access the clusters of providing, regulating cultural and total ES. ES with high Z value show that they have a high number of cluster areas with high potential of ES. The results showed that the Z-score was significantly different among services (Kruskal Wallis ANOVA =834. 607, pcultural (0.080±1.979) and regulating (0.076±1.961). These results suggested that providing services are more clustered than the remaining. Ecosystem Services Z score were

  2. Parallel analysis of tagged deletion mutants efficiently identifies genes involved in endoplasmic reticulum biogenesis.

    Science.gov (United States)

    Wright, Robin; Parrish, Mark L; Cadera, Emily; Larson, Lynnelle; Matson, Clinton K; Garrett-Engele, Philip; Armour, Chris; Lum, Pek Yee; Shoemaker, Daniel D

    2003-07-30

    Increased levels of HMG-CoA reductase induce cell type- and isozyme-specific proliferation of the endoplasmic reticulum. In yeast, the ER proliferations induced by Hmg1p consist of nuclear-associated stacks of smooth ER membranes known as karmellae. To identify genes required for karmellae assembly, we compared the composition of populations of homozygous diploid S. cerevisiae deletion mutants following 20 generations of growth with and without karmellae. Using an initial population of 1,557 deletion mutants, 120 potential mutants were identified as a result of three independent experiments. Each experiment produced a largely non-overlapping set of potential mutants, suggesting that differences in specific growth conditions could be used to maximize the comprehensiveness of similar parallel analysis screens. Only two genes, UBC7 and YAL011W, were identified in all three experiments. Subsequent analysis of individual mutant strains confirmed that each experiment was identifying valid mutations, based on the mutant's sensitivity to elevated HMG-CoA reductase and inability to assemble normal karmellae. The largest class of HMG-CoA reductase-sensitive mutations was a subset of genes that are involved in chromatin structure and transcriptional regulation, suggesting that karmellae assembly requires changes in transcription or that the presence of karmellae may interfere with normal transcriptional regulation. Copyright 2003 John Wiley & Sons, Ltd.

  3. System reliability analysis using dominant failure modes identified by selective searching technique

    International Nuclear Information System (INIS)

    Kim, Dong-Seok; Ok, Seung-Yong; Song, Junho; Koh, Hyun-Moo

    2013-01-01

    The failure of a redundant structural system is often described by innumerable system failure modes such as combinations or sequences of local failures. An efficient approach is proposed to identify dominant failure modes in the space of random variables, and then perform system reliability analysis to compute the system failure probability. To identify dominant failure modes in the decreasing order of their contributions to the system failure probability, a new simulation-based selective searching technique is developed using a genetic algorithm. The system failure probability is computed by a multi-scale matrix-based system reliability (MSR) method. Lower-scale MSR analyses evaluate the probabilities of the identified failure modes and their statistical dependence. A higher-scale MSR analysis evaluates the system failure probability based on the results of the lower-scale analyses. Three illustrative examples demonstrate the efficiency and accuracy of the approach through comparison with existing methods and Monte Carlo simulations. The results show that the proposed method skillfully identifies the dominant failure modes, including those neglected by existing approaches. The multi-scale MSR method accurately evaluates the system failure probability with statistical dependence fully considered. The decoupling between the failure mode identification and the system reliability evaluation allows for effective applications to larger structural systems

  4. Identifying Innovative Interventions to Promote Healthy Eating Using Consumption-Oriented Food Supply Chain Analysis.

    Science.gov (United States)

    Hawkes, Corinna

    2009-07-01

    The mapping and analysis of supply chains is a technique increasingly used to address problems in the food system. Yet such supply chain management has not yet been applied as a means of encouraging healthier diets. Moreover, most policies recommended to promote healthy eating focus on the consumer end of the chain. This article proposes a consumption-oriented food supply chain analysis to identify the changes needed in the food supply chain to create a healthier food environment, measured in terms of food availability, prices, and marketing. Along with established forms of supply chain analysis, the method is informed by a historical overview of how food supply chains have changed over time. The method posits that the actors and actions in the chain are affected by organizational, financial, technological, and policy incentives and disincentives, which can in turn be levered for change. It presents a preliminary example of the supply of Coca-Cola beverages into school vending machines and identifies further potential applications. These include fruit and vegetable supply chains, local food chains, supply chains for health-promoting versions of food products, and identifying financial incentives in supply chains for healthier eating.

  5. Using a Systematic Approach to Identifying Organizational Factors in Root Cause Analysis

    International Nuclear Information System (INIS)

    Gallogly, Kay Wilde

    2011-01-01

    This presentation set the scene for the second discussion session. In her presentation, the author observed that: - Investigators do not see the connection between the analysis tools available and the identification of HOF. Most investigators use the tools in a cursory manner and so do not derive the full benefits of the tools. Some tools are used for presentation purposes as opposed to being used for analytical purposes e.g. event and causal factors charts. In some cases, the report will indicate that specific analytical tools were used in the investigation but the analysis is not in the body of the report. - Some investigators are documenting HOF causes but do not recognize them as such. This indicates a lack of understanding of HOF. - Others investigators focus on technical issues because of their own comfort level. - The culture of the Organisation will affect the depth of the investigation and therefore the use of the analytical tools to pursue HOF issues. - The author contends that if analysis tools are applied systematically to gather factually based data, then HOF issues can be identified. The use of factual information (without judgement and subjectivity) is important to maintain the credibility of the investigation especially when HOF issues are identified. - Systematic use of tools assists in better communication of the issues to foster greater understanding and acceptance by senior management. - Barrier Analysis, Change Analysis, and TWIN (Task Demands, Work Environment, Individual Capabilities, and Human Nature) all offer the opportunity to identify HOF issues if the analyst pursues this line of investigation. It was illustrated that many elements of the TWIN Error Precursors are themselves Organisational in nature. - The TWIN model applied to the Anatomy of an Event will help to distinguish those which are Organisational issues (Latent Organisational Weaknesses, Error Precursors and Flawed Defences) and those which are human factors (Active Errors

  6. Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci

    Science.gov (United States)

    Tsoi, Lam C; Spain, Sarah L; Ellinghaus, Eva; Stuart, Philip E; Capon, Francesca; Knight, Jo; Tejasvi, Trilokraj; Kang, Hyun M; Allen, Michael H; Lambert, Sylviane; Stoll, Stefan; Weidinger, Stephan; Gudjonsson, Johann E; Koks, Sulev; Kingo, Külli; Esko, Tonu; Das, Sayantan; Metspalu, Andres; Weichenthal, Michael; Enerback, Charlotta; Krueger, Gerald G.; Voorhees, John J; Chandran, Vinod; Rosen, Cheryl F; Rahman, Proton; Gladman, Dafna D; Reis, Andre; Nair, Rajan P; Franke, Andre; Barker, Jonathan NWN; Abecasis, Goncalo R; Trembath, Richard C; Elder, James T

    2015-01-01

    Psoriasis is a chronic autoimmune disease with complex genetic architecture. Previous genomewide association studies (GWAS) and a recent meta-analysis using Immunochip data have uncovered 36 susceptibility loci. Here, we extend our previous meta-analysis of European ancestry by refined genotype calling and imputation and by the addition of 5,033 cases and 5,707 controls. The combined analysis, consisting of over 15,000 cases and 27,000 controls, identifies five new psoriasis susceptibility loci at genomewide significance (p < 5 × 10−8). The newly identified signals include two that reside in intergenic regions (1q31.1 and 5p13.1) and three residing near PLCL2 (3p24.3), NFKBIZ (3q12.3), and CAMK2G (10q22.2). We further demonstrate that NFKBIZ is a TRAF3IP2–dependent target of IL-17 signaling in human skin keratinocytes, thereby functionally linking two strong candidate genes. These results further integrate the genetics and immunology of psoriasis, suggesting new avenues for functional analysis and improved therapies. PMID:25939698

  7. Efficient behavior of photosynthetic organelles via Pareto optimality, identifiability, and sensitivity analysis.

    Science.gov (United States)

    Carapezza, Giovanni; Umeton, Renato; Costanza, Jole; Angione, Claudio; Stracquadanio, Giovanni; Papini, Alessio; Lió, Pietro; Nicosia, Giuseppe

    2013-05-17

    In this work, we develop methodologies for analyzing and cross comparing metabolic models. We investigate three important metabolic networks to discuss the complexity of biological organization of organisms, modeling, and system properties. In particular, we analyze these metabolic networks because of their biotechnological and basic science importance: the photosynthetic carbon metabolism in a general leaf, the Rhodobacter spheroides bacterium, and the Chlamydomonas reinhardtii alga. We adopt single- and multi-objective optimization algorithms to maximize the CO 2 uptake rate and the production of metabolites of industrial interest or for ecological purposes. We focus both on the level of genes (e.g., finding genetic manipulations to increase the production of one or more metabolites) and on finding concentration enzymes for improving the CO 2 consumption. We find that R. spheroides is able to absorb an amount of CO 2 until 57.452 mmol h (-1) gDW (-1) , while C. reinhardtii obtains a maximum of 6.7331. We report that the Pareto front analysis proves extremely useful to compare different organisms, as well as providing the possibility to investigate them with the same framework. By using the sensitivity and robustness analysis, our framework identifies the most sensitive and fragile components of the biological systems we take into account, allowing us to compare their models. We adopt the identifiability analysis to detect functional relations among enzymes; we observe that RuBisCO, GAPDH, and FBPase belong to the same functional group, as suggested also by the sensitivity analysis.

  8. Structural brain change in Attention Deficit Hyperactivity Disorder identified by meta-analysis.

    Science.gov (United States)

    Ellison-Wright, Ian; Ellison-Wright, Zoë; Bullmore, Ed

    2008-06-30

    The authors sought to map gray matter changes in Attention Deficit Hyperactivity Disorder (ADHD) using a novel technique incorporating neuro-imaging and genetic meta-analysis methods. A systematic search was conducted for voxel-based structural magnetic resonance imaging studies of patients with ADHD (or with related disorders) in relation to comparison groups. The authors carried out meta-analyses of the co-ordinates of gray matter differences. For the meta-analyses they hybridised the standard method of Activation Likelihood Estimation (ALE) with the rank approach used in Genome Scan Meta-Analysis (GSMA). This system detects three-dimensional conjunctions of co-ordinates from multiple studies and permits the weighting of studies in relation to sample size. For gray matter decreases, there were 7 studies including a total of 114 patients with ADHD (or related disorders) and 143 comparison subjects. Meta-analysis of these studies identified a significant regional gray matter reduction in ADHD in the right putamen/globus pallidus region. Four studies reported gray matter increases in ADHD but no regional increase was identified by meta-analysis. In ADHD there is gray matter reduction in the right putamen/globus pallidus region. This may be an anatomical marker for dysfunction in frontostriatal circuits mediating cognitive control. Right putamen lesions have been specifically associated with ADHD symptoms after closed head injuries in children.

  9. Structural brain change in Attention Deficit Hyperactivity Disorder identified by meta-analysis

    Directory of Open Access Journals (Sweden)

    Ellison-Wright Zoë

    2008-06-01

    Full Text Available Abstract Background The authors sought to map gray matter changes in Attention Deficit Hyperactivity Disorder (ADHD using a novel technique incorporating neuro-imaging and genetic meta-analysis methods. Methods A systematic search was conducted for voxel-based structural magnetic resonance imaging studies of patients with ADHD (or with related disorders in relation to comparison groups. The authors carried out meta-analyses of the co-ordinates of gray matter differences. For the meta-analyses they hybridised the standard method of Activation Likelihood Estimation (ALE with the rank approach used in Genome Scan Meta-Analysis (GSMA. This system detects three-dimensional conjunctions of co-ordinates from multiple studies and permits the weighting of studies in relation to sample size. Results For gray matter decreases, there were 7 studies including a total of 114 patients with ADHD (or related disorders and 143 comparison subjects. Meta-analysis of these studies identified a significant regional gray matter reduction in ADHD in the right putamen/globus pallidus region. Four studies reported gray matter increases in ADHD but no regional increase was identified by meta-analysis. Conclusion In ADHD there is gray matter reduction in the right putamen/globus pallidus region. This may be an anatomical marker for dysfunction in frontostriatal circuits mediating cognitive control. Right putamen lesions have been specifically associated with ADHD symptoms after closed head injuries in children.

  10. Gene Expression Signature Analysis Identifies Vorinostat as a Candidate Therapy for Gastric Cancer

    Science.gov (United States)

    Choi, Woonyoung; Park, Yun-Yong; Kim, KyoungHyun; Kim, Sang-Bae; Lee, Ju-Seog; Mills, Gordon B.; Cho, Jae Yong

    2011-01-01

    Background Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future. Methodology/Principal Findings Using microarray technology, we generated a gene expression profile of human gastric cancer–specific genes from human gastric cancer tissue samples. We used this profile in the Broad Institute's Connectivity Map analysis to identify candidate therapeutic compounds for gastric cancer. We found the histone deacetylase inhibitor vorinostat as the lead compound and thus a potential therapeutic drug for gastric cancer. Vorinostat induced both apoptosis and autophagy in gastric cancer cell lines. Pharmacological and genetic inhibition of autophagy however, increased the therapeutic efficacy of vorinostat, indicating that a combination of vorinostat with autophagy inhibitors may therapeutically be more beneficial. Moreover, gene expression analysis of gastric cancer identified a collection of genes (ITGB5, TYMS, MYB, APOC1, CBX5, PLA2G2A, and KIF20A) whose expression was elevated in gastric tumor tissue and downregulated more than 2-fold by vorinostat treatment in gastric cancer cell lines. In contrast, SCGB2A1, TCN1, CFD, APLP1, and NQO1 manifested a reversed pattern. Conclusions/Significance We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment. PMID:21931799

  11. Gene expression signature analysis identifies vorinostat as a candidate therapy for gastric cancer.

    Directory of Open Access Journals (Sweden)

    Sofie Claerhout

    Full Text Available Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future.Using microarray technology, we generated a gene expression profile of human gastric cancer-specific genes from human gastric cancer tissue samples. We used this profile in the Broad Institute's Connectivity Map analysis to identify candidate therapeutic compounds for gastric cancer. We found the histone deacetylase inhibitor vorinostat as the lead compound and thus a potential therapeutic drug for gastric cancer. Vorinostat induced both apoptosis and autophagy in gastric cancer cell lines. Pharmacological and genetic inhibition of autophagy however, increased the therapeutic efficacy of vorinostat, indicating that a combination of vorinostat with autophagy inhibitors may therapeutically be more beneficial. Moreover, gene expression analysis of gastric cancer identified a collection of genes (ITGB5, TYMS, MYB, APOC1, CBX5, PLA2G2A, and KIF20A whose expression was elevated in gastric tumor tissue and downregulated more than 2-fold by vorinostat treatment in gastric cancer cell lines. In contrast, SCGB2A1, TCN1, CFD, APLP1, and NQO1 manifested a reversed pattern.We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment.

  12. Identifying items to assess methodological quality in physical therapy trials: a factor analysis.

    Science.gov (United States)

    Armijo-Olivo, Susan; Cummings, Greta G; Fuentes, Jorge; Saltaji, Humam; Ha, Christine; Chisholm, Annabritt; Pasichnyk, Dion; Rogers, Todd

    2014-09-01

    Numerous tools and individual items have been proposed to assess the methodological quality of randomized controlled trials (RCTs). The frequency of use of these items varies according to health area, which suggests a lack of agreement regarding their relevance to trial quality or risk of bias. The objectives of this study were: (1) to identify the underlying component structure of items and (2) to determine relevant items to evaluate the quality and risk of bias of trials in physical therapy by using an exploratory factor analysis (EFA). A methodological research design was used, and an EFA was performed. Randomized controlled trials used for this study were randomly selected from searches of the Cochrane Database of Systematic Reviews. Two reviewers used 45 items gathered from 7 different quality tools to assess the methodological quality of the RCTs. An exploratory factor analysis was conducted using the principal axis factoring (PAF) method followed by varimax rotation. Principal axis factoring identified 34 items loaded on 9 common factors: (1) selection bias; (2) performance and detection bias; (3) eligibility, intervention details, and description of outcome measures; (4) psychometric properties of the main outcome; (5) contamination and adherence to treatment; (6) attrition bias; (7) data analysis; (8) sample size; and (9) control and placebo adequacy. Because of the exploratory nature of the results, a confirmatory factor analysis is needed to validate this model. To the authors' knowledge, this is the first factor analysis to explore the underlying component items used to evaluate the methodological quality or risk of bias of RCTs in physical therapy. The items and factors represent a starting point for evaluating the methodological quality and risk of bias in physical therapy trials. Empirical evidence of the association among these items with treatment effects and a confirmatory factor analysis of these results are needed to validate these items.

  13. Method for On-line Estimation of Electrical Motor Parameter Variation and Current Sensor Offset for SPM Motor

    Science.gov (United States)

    Uenaka, Yutaro; Sazawa, Masaki; Ohishi, Kiyoshi; Kenji, Takahashi

    The servo system of a permanent magnet (PM) motor should always maintain fine torque and fine speed responses. Accurate motor parameter identification is necessary for the PM motor servo system because the current control system is designed by considering the electric parameters of the PM motor. However, the motor parameters vary with the age of the motor and temperature. Moreover, current sensors have offset values. When the current sensor has offset values, the PM motor servo system produces torque ripple. In order to overcome these problems, this paper proposes a new real-time estimation method for both current sensor offsets and electrical parameters (resistance Ra, inductance La, and magnetic flux φfa) of the surface permanent magnet (SPM) motor. The proposed method involves the use of a real-time algorithm and a current simulator, which is operated using a DSP software system. In order to accurately estimate the motor parametera, the proposed method is using estimate currents, DC terms of sensor currents, and nominal motor parameter value. The experimental results of this study confirm that the proposed method satisfactorily estimates the current sensor offset of the U phase and V phase, as well as the electrical motor parametersRa, La, and φfa accurately.

  14. Long non-coding RNA expression profiles in gallbladder carcinoma identified using microarray analysis.

    Science.gov (United States)

    Wang, Jiwen; Liu, Han; Shen, Xiaokun; Wang, Yueqi; Zhang, Dexiang; Shen, Sheng; Suo, Tao; Pan, Hongtao; Ming, Yue; Ding, Kan; Liu, Houbao

    2017-05-01

    Gallbladder carcinoma (GBC) is the most common biliary tract cancer and exhibits poor patient prognosis. Previous studies have identified that long non-coding RNAs (lncRNAs) serve important regulatory roles in cancer biology. Alterations in lncRNAs are associated with several types of cancer. However, the contribution of lncRNAs to GBC remains unclear. To investigate the lncRNAs that are potentially involved in GBC, lncRNA profiles were identified in three pairs of human GBC and corresponding peri-carcinomatous tissue samples using microarray analysis. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate the microarray data. In order to elucidate potential functions, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and network analysis were used to determine relevant signaling pathways. Abundant RNA probes were used, and 1,758 lncRNAs and 1,254 mRNAs were detected to be differentially expressed by the microarray. Compared with para-carcinoma tissue, numerous lncRNAs were markedly upregulated or downregulated in GBC. The results demonstrated that the lncRNAs that were downregulated in GBC were more numerous compared with the lncRNAs that were upregulated. Among them, RP11-152P17.2-006 was the most upregulated, whereas CTA-941F9.9 was the most downregulated. The RT-qPCR results were consistent with the microarray data. Pathway analysis indicated that five pathways corresponded to the differentially expressed transcripts. It was demonstrated that lncRNA expression in GBC was markedly altered, and a series of novel lncRNAs associated with GBC were identified. The results of the present study suggest that the functions of lncRNAs are important in GBC development and progression.

  15. Cluster analysis identifies three urodynamic patterns in patients with orthotopic neobladder reconstruction.

    Directory of Open Access Journals (Sweden)

    Kwang Hyun Kim

    Full Text Available To classify patients with orthotopic neobladder based on urodynamic parameters using cluster analysis and to characterize the voiding function of each group.From January 2012 to November 2015, 142 patients with bladder cancer underwent radical cystectomy and Studer neobladder reconstruction at our institute. Of the 142 patients, 103 with complete urodynamic data and information on urinary functional outcomes were included in this study. K-means clustering was performed with urodynamic parameters which included maximal cystometric capacity, residual volume, maximal flow rate, compliance, and detrusor pressure at maximum flow rate. Three groups emerged by cluster analysis. Urodynamic parameters and urinary function outcomes were compared between three groups.Group 1 (n = 44 had ideal urodynamic parameters with a mean maximal bladder capacity of 513.3 ml and mean residual urine volume of 33.1 ml. Group 2 (n = 42 was characterized by small bladder capacity with low compliance. Patients in group 2 had higher rates of daytime incontinence and nighttime incontinence than patients in group 1. Group 3 (n = 17 was characterized by large residual urine volume with high compliance. When we examined gender differences in urodynamics and functional outcomes, residual urine volume and the rate of daytime incontinence were only marginally significant. However, females were significantly more likely to belong to group 2 or 3 (P = 0.003. In multivariate analysis to identify factors associated with group 1 which has the most ideal urodynamic pattern, age (OR 0.95, P = 0.017 and male gender (OR 7.57, P = 0.003 were identified as significant factors.While patients with ileal neobladder present with various voiding symptoms, three urodynamic patterns were identified by cluster analysis. Approximately half of patients had ideal urodynamic parameters. The other two groups were characterized by large residual urine and small capacity bladder with low compliance. Young

  16. Shortest-path network analysis is a useful approach toward identifying genetic determinants of longevity.

    Directory of Open Access Journals (Sweden)

    J R Managbanag

    Full Text Available BACKGROUND: Identification of genes that modulate longevity is a major focus of aging-related research and an area of intense public interest. In addition to facilitating an improved understanding of the basic mechanisms of aging, such genes represent potential targets for therapeutic intervention in multiple age-associated diseases, including cancer, heart disease, diabetes, and neurodegenerative disorders. To date, however, targeted efforts at identifying longevity-associated genes have been limited by a lack of predictive power, and useful algorithms for candidate gene-identification have also been lacking. METHODOLOGY/PRINCIPAL FINDINGS: We have utilized a shortest-path network analysis to identify novel genes that modulate longevity in Saccharomyces cerevisiae. Based on a set of previously reported genes associated with increased life span, we applied a shortest-path network algorithm to a pre-existing protein-protein interaction dataset in order to construct a shortest-path longevity network. To validate this network, the replicative aging potential of 88 single-gene deletion strains corresponding to predicted components of the shortest-path longevity network was determined. Here we report that the single-gene deletion strains identified by our shortest-path longevity analysis are significantly enriched for mutations conferring either increased or decreased replicative life span, relative to a randomly selected set of 564 single-gene deletion strains or to the current data set available for the entire haploid deletion collection. Further, we report the identification of previously unknown longevity genes, several of which function in a conserved longevity pathway believed to mediate life span extension in response to dietary restriction. CONCLUSIONS/SIGNIFICANCE: This work demonstrates that shortest-path network analysis is a useful approach toward identifying genetic determinants of longevity and represents the first application of

  17. Space-Time Analysis to Identify Areas at Risk of Mortality from Cardiovascular Disease

    Directory of Open Access Journals (Sweden)

    Poliany C. O. Rodrigues

    2015-01-01

    Full Text Available This study aimed at identifying areas that were at risk of mortality due to cardiovascular disease in residents aged 45 years or older of the cities of Cuiabá and Várzea Grande between 2009 and 2011. We conducted an ecological study of mortality rates related to cardiovascular disease. Mortality rates were calculated for each census tract by the Local Empirical Bayes estimator. High- and low-risk clusters were identified by retrospective space-time scans for each year using the Poisson probability model. We defined the year and month as the temporal analysis unit and the census tracts as the spatial analysis units adjusted by age and sex. The Mann-Whitney U test was used to compare the socioeconomic and environmental variables by risk classification. High-risk clusters showed higher income ratios than low-risk clusters, as did temperature range and atmospheric particulate matter. Low-risk clusters showed higher humidity than high-risk clusters. The Eastern region of Várzea Grande and the central region of Cuiabá were identified as areas at risk of mortality due to cardiovascular disease in individuals aged 45 years or older. High mortality risk was associated with socioeconomic and environmental factors. More high-risk clusters were observed at the end of the dry season.

  18. Messina: a novel analysis tool to identify biologically relevant molecules in disease.

    Directory of Open Access Journals (Sweden)

    Mark Pinese

    Full Text Available BACKGROUND: Morphologically similar cancers display heterogeneous patterns of molecular aberrations and follow substantially different clinical courses. This diversity has become the basis for the definition of molecular phenotypes, with significant implications for therapy. Microarray or proteomic expression profiling is conventionally employed to identify disease-associated genes, however, traditional approaches for the analysis of profiling experiments may miss molecular aberrations which define biologically relevant subtypes. METHODOLOGY/PRINCIPAL FINDINGS: Here we present Messina, a method that can identify those genes that only sometimes show aberrant expression in cancer. We demonstrate with simulated data that Messina is highly sensitive and specific when used to identify genes which are aberrantly expressed in only a proportion of cancers, and compare Messina to contemporary analysis techniques. We illustrate Messina by using it to detect the aberrant expression of a gene that may play an important role in pancreatic cancer. CONCLUSIONS/SIGNIFICANCE: Messina allows the detection of genes with profiles typical of markers of molecular subtype, and complements existing methods to assist the identification of such markers. Messina is applicable to any global expression profiling data, and to allow its easy application has been packaged into a freely-available stand-alone software package.

  19. Identifying fine sediment sources to alleviate flood risk caused by fine sediments through catchment connectivity analysis

    Science.gov (United States)

    Twohig, Sarah; Pattison, Ian; Sander, Graham

    2017-04-01

    Fine sediment poses a significant threat to UK river systems in terms of vegetation, aquatic habitats and morphology. Deposition of fine sediment onto the river bed reduces channel capacity resulting in decreased volume to contain high flow events. Once the in channel problem has been identified managers are under pressure to sustainably mitigate flood risk. With climate change and land use adaptations increasing future pressures on river catchments it is important to consider the connectivity of fine sediment throughout the river catchment and its influence on channel capacity, particularly in systems experiencing long term aggradation. Fine sediment erosion is a continuing concern in the River Eye, Leicestershire. The predominately rural catchment has a history of flooding within the town of Melton Mowbray. Fine sediment from agricultural fields has been identified as a major contributor of sediment delivery into the channel. Current mitigation measures are not sustainable or successful in preventing the continuum of sediment throughout the catchment. Identifying the potential sources and connections of fine sediment would provide insight into targeted catchment management. 'Sensitive Catchment Integrated Modelling Analysis Platforms' (SCIMAP) is a tool often used by UK catchment managers to identify potential sources and routes of sediment within a catchment. SCIMAP is a risk based model that combines hydrological (rainfall) and geomorphic controls (slope, land cover) to identify the risk of fine sediment being transported from source into the channel. A desktop version of SCIMAP was run for the River Eye at a catchment scale using 5m terrain, rainfall and land cover data. A series of SCIMAP model runs were conducted changing individual parameters to determine the sensitivity of the model. Climate Change prediction data for the catchment was used to identify potential areas of future connectivity and erosion risk for catchment managers. The results have been

  20. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration.

    Science.gov (United States)

    de Vries, Paul S; Chasman, Daniel I; Sabater-Lleal, Maria; Chen, Ming-Huei; Huffman, Jennifer E; Steri, Maristella; Tang, Weihong; Teumer, Alexander; Marioni, Riccardo E; Grossmann, Vera; Hottenga, Jouke J; Trompet, Stella; Müller-Nurasyid, Martina; Zhao, Jing Hua; Brody, Jennifer A; Kleber, Marcus E; Guo, Xiuqing; Wang, Jie Jin; Auer, Paul L; Attia, John R; Yanek, Lisa R; Ahluwalia, Tarunveer S; Lahti, Jari; Venturini, Cristina; Tanaka, Toshiko; Bielak, Lawrence F; Joshi, Peter K; Rocanin-Arjo, Ares; Kolcic, Ivana; Navarro, Pau; Rose, Lynda M; Oldmeadow, Christopher; Riess, Helene; Mazur, Johanna; Basu, Saonli; Goel, Anuj; Yang, Qiong; Ghanbari, Mohsen; Willemsen, Gonneke; Rumley, Ann; Fiorillo, Edoardo; de Craen, Anton J M; Grotevendt, Anne; Scott, Robert; Taylor, Kent D; Delgado, Graciela E; Yao, Jie; Kifley, Annette; Kooperberg, Charles; Qayyum, Rehan; Lopez, Lorna M; Berentzen, Tina L; Räikkönen, Katri; Mangino, Massimo; Bandinelli, Stefania; Peyser, Patricia A; Wild, Sarah; Trégouët, David-Alexandre; Wright, Alan F; Marten, Jonathan; Zemunik, Tatijana; Morrison, Alanna C; Sennblad, Bengt; Tofler, Geoffrey; de Maat, Moniek P M; de Geus, Eco J C; Lowe, Gordon D; Zoledziewska, Magdalena; Sattar, Naveed; Binder, Harald; Völker, Uwe; Waldenberger, Melanie; Khaw, Kay-Tee; Mcknight, Barbara; Huang, Jie; Jenny, Nancy S; Holliday, Elizabeth G; Qi, Lihong; Mcevoy, Mark G; Becker, Diane M; Starr, John M; Sarin, Antti-Pekka; Hysi, Pirro G; Hernandez, Dena G; Jhun, Min A; Campbell, Harry; Hamsten, Anders; Rivadeneira, Fernando; Mcardle, Wendy L; Slagboom, P Eline; Zeller, Tanja; Koenig, Wolfgang; Psaty, Bruce M; Haritunians, Talin; Liu, Jingmin; Palotie, Aarno; Uitterlinden, André G; Stott, David J; Hofman, Albert; Franco, Oscar H; Polasek, Ozren; Rudan, Igor; Morange, Pierre-Emmanuel; Wilson, James F; Kardia, Sharon L R; Ferrucci, Luigi; Spector, Tim D; Eriksson, Johan G; Hansen, Torben; Deary, Ian J; Becker, Lewis C; Scott, Rodney J; Mitchell, Paul; März, Winfried; Wareham, Nick J; Peters, Annette; Greinacher, Andreas; Wild, Philipp S; Jukema, J Wouter; Boomsma, Dorret I; Hayward, Caroline; Cucca, Francesco; Tracy, Russell; Watkins, Hugh; Reiner, Alex P; Folsom, Aaron R; Ridker, Paul M; O'Donnell, Christopher J; Smith, Nicholas L; Strachan, David P; Dehghan, Abbas

    2016-01-15

    Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. We conducted a genome-wide association analysis of 34 studies imputed to the 1000 Genomes Project reference panel and including ∼120 000 participants of European ancestry (95 806 participants with data on the X-chromosome). Approximately 10.7 million single-nucleotide polymorphisms and 1.2 million indels were examined. We identified 41 genome-wide significant fibrinogen loci; of which, 18 were newly identified. There were no genome-wide significant signals on the X-chromosome. The lead variants of five significant loci were indels. We further identified six additional independent signals, including three rare variants, at two previously characterized loci: FGB and IRF1. Together the 41 loci explain 3% of the variance in plasma fibrinogen concentration. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Integrating Stakeholder Preferences and GIS-Based Multicriteria Analysis to Identify Forest Landscape Restoration Priorities

    Directory of Open Access Journals (Sweden)

    David Uribe

    2014-02-01

    Full Text Available A pressing question that arises during the planning of an ecological restoration process is: where to restore first? Answering this question is a complex task; it requires a multidimensional approach to consider economic constrains and the preferences of stakeholders. Being the problem of spatial nature, it may be explored effectively through Multicriteria Decision Analysis (MCDA performed in a Geographical Information System (GIS environment. The proposed approach is based on the definition and weighting of multiple criteria for evaluating land suitability. An MCDA-based methodology was used to identify priority areas for Forest Landscape Restoration in the Upper Mixtec region, Oaxaca (Mexico, one of the most degraded areas of Latin America. Socioeconomic and environmental criteria were selected and evaluated. The opinions of four different stakeholder groups were considered: general public, academic, Non-governmental organizations (NGOs and governmental officers. The preferences of these groups were spatially modeled to identify their priorities. The final result was a map that identifies the most preferable sites for restoration, where resources and efforts should be concentrated. MCDA proved to be a very useful tool in collective planning, when alternative sites have to be identified and prioritized to guide the restoration work.

  2. The systematic functional analysis of plasmodium protein kinases identifies essential regulators of mosquito transmission

    KAUST Repository

    Tewari, Rita

    2010-10-21

    Although eukaryotic protein kinases (ePKs) contribute to many cellular processes, only three Plasmodium falciparum ePKs have thus far been identified as essential for parasite asexual blood stage development. To identify pathways essential for parasite transmission between their mammalian host and mosquito vector, we undertook a systematic functional analysis of ePKs in the genetically tractable rodent parasite Plasmodium berghei. Modeling domain signatures of conventional ePKs identified 66 putative Plasmodium ePKs. Kinomes are highly conserved between Plasmodium species. Using reverse genetics, we show that 23 ePKs are redundant for asexual erythrocytic parasite development in mice. Phenotyping mutants at four life cycle stages in Anopheles stephensi mosquitoes revealed functional clusters of kinases required for sexual development and sporogony. Roles for a putative SR protein kinase (SRPK) in microgamete formation, a conserved regulator of clathrin uncoating (GAK) in ookinete formation, and a likely regulator of energy metabolism (SNF1/KIN) in sporozoite development were identified. 2010 Elsevier Inc.

  3. Genetic analysis of atherosclerosis identifies a major susceptibility locus in the major histocompatibility complex of mice.

    Science.gov (United States)

    Grainger, Andrew T; Jones, Michael B; Li, Jing; Chen, Mei-Hua; Manichaikul, Ani; Shi, Weibin

    2016-11-01

    Recent genome-wide association studies (GWAS) have identified over 50 significant loci containing common variants associated with coronary artery disease. However, these variants explain only 26% of the genetic heritability of the disease, suggesting that many more variants remain to be discovered. Here, we examined the genetic basis underlying the marked difference between SM/J-Apoe -/- and BALB/cJ-Apoe -/- mice in atherosclerotic lesion formation. 206 female F 2 mice generated from an intercross between the two Apoe -/- strains were fed 12 weeks of western diet. Atherosclerotic lesion sizes in the aortic root were measured and 149 genetic markers genotyped across the entire genome. A significant locus, named Ath49 (LOD score: 4.18), for atherosclerosis was mapped to the H2 complex [mouse major histocompatibility complex (MHC)] on chromosome 17. Bioinformatic analysis identified 12 probable candidate genes, including Tnfrsf21, Adgrf1, Adgrf5, Mep1a, and Pla2g7. Corresponding human genomic regions of Ath49 showed significant association with coronary heart disease. Five suggestive loci on chromosomes 1, 4, 5, and 8 for atherosclerosis were also identified. Atherosclerotic lesion sizes were significantly correlated with HDL but not with non-HDL cholesterol, triglyceride or glucose levels in the F 2 cohort. We have identified the MHC as a major genetic determinant of atherosclerosis, highlighting the importance of inflammation in atherogenesis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  4. Pathway cross-talk network analysis identifies critical pathways in neonatal sepsis.

    Science.gov (United States)

    Meng, Yu-Xiu; Liu, Quan-Hong; Chen, Deng-Hong; Meng, Ying

    2017-06-01

    Despite advances in neonatal care, sepsis remains a major cause of morbidity and mortality in neonates worldwide. Pathway cross-talk analysis might contribute to the inference of the driving forces in bacterial sepsis and facilitate a better understanding of underlying pathogenesis of neonatal sepsis. This study aimed to explore the critical pathways associated with the progression of neonatal sepsis by the pathway cross-talk analysis. By integrating neonatal transcriptome data with known pathway data and protein-protein interaction data, we systematically uncovered the disease pathway cross-talks and constructed a disease pathway cross-talk network for neonatal sepsis. Then, attract method was employed to explore the dysregulated pathways associated with neonatal sepsis. To determine the critical pathways in neonatal sepsis, rank product (RP) algorithm, centrality analysis and impact factor (IF) were introduced sequentially, which synthetically considered the differential expression of genes and pathways, pathways cross-talks and pathway parameters in the network. The dysregulated pathways with the highest IF values as well as RPpathways in neonatal sepsis. By integrating three kinds of data, only 6919 common genes were included to perform the pathway cross-talk analysis. By statistic analysis, a total of 1249 significant pathway cross-talks were selected to construct the pathway cross-talk network. Moreover, 47 dys-regulated pathways were identified via attract method, 20 pathways were identified under RPpathways with the highest IF were also screened from the pathway cross-talk network. Among them, we selected 8 common pathways, i.e. critical pathways. In this study, we systematically tracked 8 critical pathways involved in neonatal sepsis by integrating attract method and pathway cross-talk network. These pathways might be responsible for the host response in infection, and of great value for advancing diagnosis and therapy of neonatal sepsis. Copyright © 2017

  5. BAYESIAN ANALYSIS TO IDENTIFY NEW STAR CANDIDATES IN NEARBY YOUNG STELLAR KINEMATIC GROUPS

    International Nuclear Information System (INIS)

    Malo, Lison; Doyon, René; Lafrenière, David; Artigau, Étienne; Gagné, Jonathan; Baron, Frédérique; Riedel, Adric

    2013-01-01

    We present a new method based on a Bayesian analysis to identify new members of nearby young kinematic groups. The analysis minimally takes into account the position, proper motion, magnitude, and color of a star, but other observables can be readily added (e.g., radial velocity, distance). We use this method to find new young low-mass stars in the β Pictoris and AB Doradus moving groups and in the TW Hydrae, Tucana-Horologium, Columba, Carina, and Argus associations. Starting from a sample of 758 mid-K to mid-M (K5V-M5V) stars showing youth indicators such as Hα and X-ray emission, our analysis yields 214 new highly probable low-mass members of the kinematic groups analyzed. One is in TW Hydrae, 37 in β Pictoris, 17 in Tucana-Horologium, 20 in Columba, 6 in Carina, 50 in Argus, 32 in AB Doradus, and the remaining 51 candidates are likely young but have an ambiguous membership to more than one association. The false alarm rate for new candidates is estimated to be 5% for β Pictoris and TW Hydrae, 10% for Tucana-Horologium, Columba, Carina, and Argus, and 14% for AB Doradus. Our analysis confirms the membership of 58 stars proposed in the literature. Firm membership confirmation of our new candidates will require measurement of their radial velocity (predicted by our analysis), parallax, and lithium 6708 Å equivalent width. We have initiated these follow-up observations for a number of candidates, and we have identified two stars (2MASSJ01112542+1526214, 2MASSJ05241914-1601153) as very strong candidate members of the β Pictoris moving group and one strong candidate member (2MASSJ05332558-5117131) of the Tucana-Horologium association; these three stars have radial velocity measurements confirming their membership and lithium detections consistent with young age.

  6. Practical In-Depth Analysis of IDS Alerts for Tracing and Identifying Potential Attackers on Darknet

    Directory of Open Access Journals (Sweden)

    Jungsuk Song

    2017-02-01

    Full Text Available The darknet (i.e., a set of unused IP addresses is a very useful solution for observing the global trends of cyber threats and analyzing attack activities on the Internet. Since the darknet is not connected with real systems, in most cases, the incoming packets on the darknet (‘the darknet traffic’ do not contain a payload. This means that we are unable to get real malware from the darknet traffic. This situation makes it difficult for security experts (e.g., academic researchers, engineers, operators, etc. to identify whether the source hosts of the darknet traffic are infected by real malware or not. In this paper, we present the overall procedure of the in-depth analysis between the darknet traffic and IDS alerts using real data collected at the Science and Technology Cyber Security Center (S&T CSC in Korea and provide the detailed in-depth analysis results. The ultimate goal of this paper is to provide practical experience, insight and know-how to security experts so that they are able to identify and trace the root cause of the darknet traffic. The experimental results show that correlation analysis between the darknet traffic and IDS alerts is very useful to discover potential attack hosts, especially internal hosts, and to find out what kinds of malware infected them.

  7. Integrated in vivo multiomics analysis identifies p21-activated kinase signaling as a driver of colitis.

    Science.gov (United States)

    Lyons, Jesse; Brubaker, Douglas K; Ghazi, Phaedra C; Baldwin, Katherine R; Edwards, Amanda; Boukhali, Myriam; Strasser, Samantha Dale; Suarez-Lopez, Lucia; Lin, Yi-Jang; Yajnik, Vijay; Kissil, Joseph L; Haas, Wilhelm; Lauffenburger, Douglas A; Haigis, Kevin M

    2018-02-27

    Inflammatory bowel disease (IBD) is a chronic disorder of the gastrointestinal tract that has limited treatment options. To gain insight into the pathogenesis of chronic colonic inflammation (colitis), we performed a multiomics analysis that integrated RNA microarray, total protein mass spectrometry (MS), and phosphoprotein MS measurements from a mouse model of the disease. Because we collected all three types of data from individual samples, we tracked information flow from RNA to protein to phosphoprotein and identified signaling molecules that were coordinately or discordantly regulated and pathways that had complex regulation in vivo. For example, the genes encoding acute-phase proteins were expressed in the liver, but the proteins were detected by MS in the colon during inflammation. We also ascertained the types of data that best described particular facets of chronic inflammation. Using gene set enrichment analysis and trans-omics coexpression network analysis, we found that each data set provided a distinct viewpoint on the molecular pathogenesis of colitis. Combining human transcriptomic data with the mouse multiomics data implicated increased p21-activated kinase (Pak) signaling as a driver of colitis. Chemical inhibition of Pak1 and Pak2 with FRAX597 suppressed active colitis in mice. These studies provide translational insights into the mechanisms contributing to colitis and identify Pak as a potential therapeutic target in IBD. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  8. Using sensitivity analysis to identify key factors for the propagation of a plant epidemic.

    Science.gov (United States)

    Rimbaud, Loup; Bruchou, Claude; Dallot, Sylvie; Pleydell, David R J; Jacquot, Emmanuel; Soubeyrand, Samuel; Thébaud, Gaël

    2018-01-01

    Identifying the key factors underlying the spread of a disease is an essential but challenging prerequisite to design management strategies. To tackle this issue, we propose an approach based on sensitivity analyses of a spatiotemporal stochastic model simulating the spread of a plant epidemic. This work is motivated by the spread of sharka, caused by plum pox virus , in a real landscape. We first carried out a broad-range sensitivity analysis, ignoring any prior information on six epidemiological parameters, to assess their intrinsic influence on model behaviour. A second analysis benefited from the available knowledge on sharka epidemiology and was thus restricted to more realistic values. The broad-range analysis revealed that the mean duration of the latent period is the most influential parameter of the model, whereas the sharka-specific analysis uncovered the strong impact of the connectivity of the first infected orchard. In addition to demonstrating the interest of sensitivity analyses for a stochastic model, this study highlights the impact of variation ranges of target parameters on the outcome of a sensitivity analysis. With regard to sharka management, our results suggest that sharka surveillance may benefit from paying closer attention to highly connected patches whose infection could trigger serious epidemics.

  9. Identifying the new Influencers in the Internet Era: Social Media and Social Network Analysis

    Directory of Open Access Journals (Sweden)

    MIGUEL DEL FRESNO GARCÍA

    2016-01-01

    Full Text Available Social media influencers (SMIs can be defined as a new type of independent actor who are able to shape audience attitudes through the use of social media channels in competition and coexistence with professional media. Being able to accurately identify SMIs is critical no matter what is being transmitted in a social system. Social Network Analysis (SNA has been recognized as a powerful tool for representing social network structures and information dissemination. SMIs can be identifi ed by their high-ranking position in a network as the most important or central nodes. The results reveal the existence of three different typologies of SMIs: disseminator, engager and leader. This methodology permits the optimization of resources to create effective online communication strategies.

  10. New families of human regulatory RNA structures identified by comparative analysis of vertebrate genomes

    DEFF Research Database (Denmark)

    Parker, Brian John; Moltke, Ida; Roth, Adam

    2011-01-01

    a comparative method, EvoFam, for genome-wide identification of families of regulatory RNA structures, based on primary sequence and secondary structure similarity. We apply EvoFam to a 41-way genomic vertebrate alignment. Genome-wide, we identify 220 human, high-confidence families outside protein...... identify tens of new families supported by strong evolutionary evidence and other statistical evidence, such as GO term enrichments. For some of these, detailed analysis has led to the formulation of specific functional hypotheses. Examples include two hypothesized auto-regulatory feedback mechanisms: one...... involving six long hairpins in the 3'-UTR of MAT2A, a key metabolic gene that produces the primary human methyl donor S-adenosylmethionine; the other involving a tRNA-like structure in the intron of the tRNA maturation gene POP1. We experimentally validate the predicted MAT2A structures. Finally, we...

  11. Identifying patients with therapy-resistant depression by using factor analysis

    DEFF Research Database (Denmark)

    Andreasson, K; Liest, V; Lunde, M

    2010-01-01

    INTRODUCTION: Attempts to identify the factor structure in patients with treatment-resistant depression have been very limited. METHODS: Principal component analysis was performed using the baseline datasets from 3 add-on studies [2 with repetitive transcranial magnetic stimulation and one...... with transcranial pulsed electromagnetic fields (T-PEMF)], in which the relative effect as percentage of improvement during the treatment period was analysed. RESULTS: We identified 2 major factors, the first of which was a general factor. The second was a dual factor consisting of a depression subscale comprising...... the negatively loaded items (covering the pure depression items) and a treatment resistant subscale comprising the positively loaded items (covering lassitude, concentration difficulties and sleep problems). These 2 dual subscales were used as outcome measures. Improvement on the treatment resistant subscale...

  12. A cross-study gene set enrichment analysis identifies critical pathways in endometriosis

    Directory of Open Access Journals (Sweden)

    Bai Chunyan

    2009-09-01

    Full Text Available Abstract Background Endometriosis is an enigmatic disease. Gene expression profiling of endometriosis has been used in several studies, but few studies went further to classify subtypes of endometriosis based on expression patterns and to identify possible pathways involved in endometriosis. Some of the observed pathways are more inconsistent between the studies, and these candidate pathways presumably only represent a fraction of the pathways involved in endometriosis. Methods We applied a standardised microarray preprocessing and gene set enrichment analysis to six independent studies, and demonstrated increased concordance between these gene datasets. Results We find 16 up-regulated and 19 down-regulated pathways common in ovarian endometriosis data sets, 22 up-regulated and one down-regulated pathway common in peritoneal endometriosis data sets. Among them, 12 up-regulated and 1 down-regulated were found consistent between ovarian and peritoneal endometriosis. The main canonical pathways identified are related to immunological and inflammatory disease. Early secretory phase has the most over-represented pathways in the three uterine cycle phases. There are no overlapping significant pathways between the dataset from human endometrial endothelial cells and the datasets from ovarian endometriosis which used whole tissues. Conclusion The study of complex diseases through pathway analysis is able to highlight genes weakly connected to the phenotype which may be difficult to detect by using classical univariate statistics. By standardised microarray preprocessing and GSEA, we have increased the concordance in identifying many biological mechanisms involved in endometriosis. The identified gene pathways will shed light on the understanding of endometriosis and promote the development of novel therapies.

  13. Gene-network analysis identifies susceptibility genes related to glycobiology in autism.

    Directory of Open Access Journals (Sweden)

    Bert van der Zwaag

    Full Text Available The recent identification of copy-number variation in the human genome has opened up new avenues for the discovery of positional candidate genes underlying complex genetic disorders, especially in the field of psychiatric disease. One major challenge that remains is pinpointing the susceptibility genes in the multitude of disease-associated loci. This challenge may be tackled by reconstruction of functional gene-networks from the genes residing in these loci. We applied this approach to autism spectrum disorder (ASD, and identified the copy-number changes in the DNA of 105 ASD patients and 267 healthy individuals with Illumina Humanhap300 Beadchips. Subsequently, we used a human reconstructed gene-network, Prioritizer, to rank candidate genes in the segmental gains and losses in our autism cohort. This analysis highlighted several candidate genes already known to be mutated in cognitive and neuropsychiatric disorders, including RAI1, BRD1, and LARGE. In addition, the LARGE gene was part of a sub-network of seven genes functioning in glycobiology, present in seven copy-number changes specifically identified in autism patients with limited co-morbidity. Three of these seven copy-number changes were de novo in the patients. In autism patients with a complex phenotype and healthy controls no such sub-network was identified. An independent systematic analysis of 13 published autism susceptibility loci supports the involvement of genes related to glycobiology as we also identified the same or similar genes from those loci. Our findings suggest that the occurrence of genomic gains and losses of genes associated with glycobiology are important contributors to the development of ASD.

  14. Systematic enrichment analysis of gene expression profiling studies identifies consensus pathways implicated in colorectal cancer development

    Directory of Open Access Journals (Sweden)

    Jesús Lascorz

    2011-01-01

    Full Text Available Background: A large number of gene expression profiling (GEP studies on colorectal carcinogenesis have been performed but no reliable gene signature has been identified so far due to the lack of reproducibility in the reported genes. There is growing evidence that functionally related genes, rather than individual genes, contribute to the etiology of complex traits. We used, as a novel approach, pathway enrichment tools to define functionally related genes that are consistently up- or down-regulated in colorectal carcinogenesis. Materials and Methods: We started the analysis with 242 unique annotated genes that had been reported by any of three recent meta-analyses covering GEP studies on genes differentially expressed in carcinoma vs normal mucosa. Most of these genes (218, 91.9% had been reported in at least three GEP studies. These 242 genes were submitted to bioinformatic analysis using a total of nine tools to detect enrichment of Gene Ontology (GO categories or Kyoto Encyclopedia of Genes and Genomes (KEGG pathways. As a final consistency criterion the pathway categories had to be enriched by several tools to be taken into consideration. Results: Our pathway-based enrichment analysis identified the categories of ribosomal protein constituents, extracellular matrix receptor interaction, carbonic anhydrase isozymes, and a general category related to inflammation and cellular response as significantly and consistently overrepresented entities. Conclusions: We triaged the genes covered by the published GEP literature on colorectal carcinogenesis and subjected them to multiple enrichment tools in order to identify the consistently enriched gene categories. These turned out to have known functional relationships to cancer development and thus deserve further investigation.

  15. Towards a typology of business process management professionals: identifying patterns of competences through latent semantic analysis

    DEFF Research Database (Denmark)

    Müller, Oliver; Schmiedel, Theresa; Gorbacheva, Elena

    2014-01-01

    -related job advertisements in order to develop a typology of BPM professionals. This empirical analysis reveals distinct ideal types and profiles of BPM professionals on several levels of abstraction. A closer look at these ideal types and profiles confirms that BPM is a boundary-spanning field that requires...... interdisciplinary sets of competence that range from technical competences to business and systems competences. Based on the study’s findings, it is posited that individual and organisational alignment with the identified ideal types and profiles is likely to result in high employability and organisational BPM...

  16. Comparing chemical analysis with literature studies to identify micropollutants in a catchment of Copenhagen (DK)

    DEFF Research Database (Denmark)

    Lützhøft, Hans-Christian Holten; Birch, Heidi; Eriksson, Eva

    2011-01-01

    on urban surface runoff originating from a well defined catchment of Copenhagen (Denmark) with an inventory of potential pollution sources for the same catchment. The selected catchment covers an area with roads, a shopping centre, a parking lot, office buildings, a gymnasium and some restaurants....... The literature approach is limited to the range of included PSs and to how and which information is compiled, whereas the analytical chemical approach is limited to the selection of analyzed substances, sensitivity and precision. Comparing the two approaches of chemical analysis with literature study to identify...

  17. Towards a typology of business process management professionals: identifying patterns of competences through latent semantic analysis

    Science.gov (United States)

    Müller, Oliver; Schmiedel, Theresa; Gorbacheva, Elena; vom Brocke, Jan

    2016-01-01

    While researchers have analysed the organisational competences that are required for successful Business Process Management (BPM) initiatives, individual BPM competences have not yet been studied in detail. In this study, latent semantic analysis is used to examine a collection of 1507 BPM-related job advertisements in order to develop a typology of BPM professionals. This empirical analysis reveals distinct ideal types and profiles of BPM professionals on several levels of abstraction. A closer look at these ideal types and profiles confirms that BPM is a boundary-spanning field that requires interdisciplinary sets of competence that range from technical competences to business and systems competences. Based on the study's findings, it is posited that individual and organisational alignment with the identified ideal types and profiles is likely to result in high employability and organisational BPM success.

  18. Independent component analysis of high-resolution imaging data identifies distinct functional domains

    DEFF Research Database (Denmark)

    Reidl, Juergen; Starke, Jens; Omer, David

    2007-01-01

    . Here we demonstrate that principal component analysis (PCA) followed by spatial independent component analysis (sICA), can be exploited to reduce the dimensionality of data sets recorded in the olfactory bulb and the somatosensory cortex of mice as well as the visual cortex of monkeys, without loosing...... latencies can be identified. This is shown for recordings of olfactory receptor neuron input measured with a calcium sensitive axon tracer and for network dynamics measured with the voltage sensitive dye RH 1838. In the somatosensory cortex, barrels responding to the stimulation of single whiskers can...... be automatically detected. In the visual cortex orientation columns can be extracted. In all cases artifacts due to movement, heartbeat or respiration were separated from the functional signal by sICA and could be removed from the data set. sICA is therefore a powerful technique for data compression, unbiased...

  19. Polygenic analysis of genome-wide SNP data identifies common variants on allergic rhinitis

    DEFF Research Database (Denmark)

    Mohammadnejad, Afsaneh; Brasch-Andersen, Charlotte; Haagerup, Annette

    Background: Allergic Rhinitis (AR) is a complex disorder that affects many people around the world. There is a high genetic contribution to the development of the AR, as twins and family studies have estimated heritability of more than 33%. Due to the complex nature of the disease, single SNP...... analysis has limited power in identifying the genetic variations for AR. We combined genome-wide association analysis (GWAS) with polygenic risk score (PRS) in exploring the genetic basis underlying the disease. Methods: We collected clinical data on 631 Danish subjects with AR cases consisting of 434...... sibling pairs and unrelated individuals and control subjects of 197 unrelated individuals. SNP genotyping was done by Affymetrix Genome-Wide Human SNP Array 5.0. SNP imputation was performed using "IMPUTE2". Using additive effect model, GWAS was conducted in discovery sample, the genotypes...

  20. Whole Genome Analysis of Injectional Anthrax Identifies Two Disease Clusters Spanning More Than 13 Years

    Directory of Open Access Journals (Sweden)

    Paul Keim

    2015-11-01

    Lay Person Interpretation: Injectional anthrax has been plaguing heroin drug users across Europe for more than 10 years. In order to better understand this outbreak, we assessed genomic relationships of all available injectional anthrax strains from four countries spanning a >12 year period. Very few differences were identified using genome-based analysis, but these differentiated the isolates into two distinct clusters. This strongly supports a hypothesis of at least two separate anthrax spore contamination events perhaps during the drug production processes. Identification of two events would not have been possible from standard epidemiological analysis. These comprehensive data will be invaluable for classifying future injectional anthrax isolates and for future geographic attribution.

  1. Identifying changes in the support networks of end-of-life carers using social network analysis.

    Science.gov (United States)

    Leonard, Rosemary; Horsfall, Debbie; Noonan, Kerrie

    2015-06-01

    End-of-life caring is often associated with reduced social networks for both the dying person and for the carer. However, those adopting a community participation and development approach, see the potential for the expansion and strengthening of networks. This paper uses Knox, Savage and Harvey's definitions of three generations social network analysis to analyse the caring networks of people with a terminal illness who are being cared for at home and identifies changes in these caring networks that occurred over the period of caring. Participatory network mapping of initial and current networks was used in nine focus groups. The analysis used key concepts from social network analysis (size, density, transitivity, betweenness and local clustering) together with qualitative analyses of the group's reflections on the maps. The results showed an increase in the size of the networks and that ties between the original members of the network strengthened. The qualitative data revealed the importance between core and peripheral network members and the diverse contributions of the network members. The research supports the value of third generation social network analysis and the potential for end-of-life caring to build social capital. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  2. Distinct Phenotypes of Smokers with Fixed Airflow Limitation Identified by Cluster Analysis of Severe Asthma.

    Science.gov (United States)

    Konno, Satoshi; Taniguchi, Natsuko; Makita, Hironi; Nakamaru, Yuji; Shimizu, Kaoruko; Shijubo, Noriharu; Fuke, Satoshi; Takeyabu, Kimihiro; Oguri, Mitsuru; Kimura, Hirokazu; Maeda, Yukiko; Suzuki, Masaru; Nagai, Katsura; Ito, Yoichi M; Wenzel, Sally E; Nishimura, Masaharu

    2018-01-01

    Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses. To explore novel severe asthma phenotypes by cluster analysis when including smoking patients with asthma. We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Clinical variables obtained during a 2-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters. Five clinical clusters, including two characterized by low forced expiratory volume in 1 second/forced vital capacity, were identified. When characteristics of smoking subjects in these two clusters were compared, there were marked differences between the two groups: one had high levels of circulating eosinophils, high immunoglobulin E levels, and a high sinus score, and the other was characterized by low levels of the same parameters. Sputum analysis revealed intriguing differences of cytokine/chemokine pattern in these two groups. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 3 years later. This study reveals two distinct phenotypes with potentially different biological pathways contributing to fixed airflow limitation in cigarette smokers with severe asthma.

  3. Application of cluster analysis to geochemical compositional data for identifying ore-related geochemical anomalies

    Science.gov (United States)

    Zhou, Shuguang; Zhou, Kefa; Wang, Jinlin; Yang, Genfang; Wang, Shanshan

    2017-12-01

    Cluster analysis is a well-known technique that is used to analyze various types of data. In this study, cluster analysis is applied to geochemical data that describe 1444 stream sediment samples collected in northwestern Xinjiang with a sample spacing of approximately 2 km. Three algorithms (the hierarchical, k-means, and fuzzy c-means algorithms) and six data transformation methods (the z-score standardization, ZST; the logarithmic transformation, LT; the additive log-ratio transformation, ALT; the centered log-ratio transformation, CLT; the isometric log-ratio transformation, ILT; and no transformation, NT) are compared in terms of their effects on the cluster analysis of the geochemical compositional data. The study shows that, on the one hand, the ZST does not affect the results of column- or variable-based (R-type) cluster analysis, whereas the other methods, including the LT, the ALT, and the CLT, have substantial effects on the results. On the other hand, the results of the row- or observation-based (Q-type) cluster analysis obtained from the geochemical data after applying NT and the ZST are relatively poor. However, we derive some improved results from the geochemical data after applying the CLT, the ILT, the LT, and the ALT. Moreover, the k-means and fuzzy c-means clustering algorithms are more reliable than the hierarchical algorithm when they are used to cluster the geochemical data. We apply cluster analysis to the geochemical data to explore for Au deposits within the study area, and we obtain a good correlation between the results retrieved by combining the CLT or the ILT with the k-means or fuzzy c-means algorithms and the potential zones of Au mineralization. Therefore, we suggest that the combination of the CLT or the ILT with the k-means or fuzzy c-means algorithms is an effective tool to identify potential zones of mineralization from geochemical data.

  4. Identifying Talent in Youth Sport: A Novel Methodology Using Higher-Dimensional Analysis.

    Directory of Open Access Journals (Sweden)

    Kevin Till

    Full Text Available Prediction of adult performance from early age talent identification in sport remains difficult. Talent identification research has generally been performed using univariate analysis, which ignores multivariate relationships. To address this issue, this study used a novel higher-dimensional model to orthogonalize multivariate anthropometric and fitness data from junior rugby league players, with the aim of differentiating future career attainment. Anthropometric and fitness data from 257 Under-15 rugby league players was collected. Players were grouped retrospectively according to their future career attainment (i.e., amateur, academy, professional. Players were blindly and randomly divided into an exploratory (n = 165 and validation dataset (n = 92. The exploratory dataset was used to develop and optimize a novel higher-dimensional model, which combined singular value decomposition (SVD with receiver operating characteristic analysis. Once optimized, the model was tested using the validation dataset. SVD analysis revealed 60 m sprint and agility 505 performance were the most influential characteristics in distinguishing future professional players from amateur and academy players. The exploratory dataset model was able to distinguish between future amateur and professional players with a high degree of accuracy (sensitivity = 85.7%, specificity = 71.1%; p<0.001, although it could not distinguish between future professional and academy players. The validation dataset model was able to distinguish future professionals from the rest with reasonable accuracy (sensitivity = 83.3%, specificity = 63.8%; p = 0.003. Through the use of SVD analysis it was possible to objectively identify criteria to distinguish future career attainment with a sensitivity over 80% using anthropometric and fitness data alone. As such, this suggests that SVD analysis may be a useful analysis tool for research and practice within talent identification.

  5. Single Molecule Cluster Analysis Identifies Signature Dynamic Conformations along the Splicing Pathway

    Science.gov (United States)

    Blanco, Mario R.; Martin, Joshua S.; Kahlscheuer, Matthew L.; Krishnan, Ramya; Abelson, John; Laederach, Alain; Walter, Nils G.

    2016-01-01

    The spliceosome is the dynamic RNA-protein machine responsible for faithfully splicing introns from precursor messenger RNAs (pre-mRNAs). Many of the dynamic processes required for the proper assembly, catalytic activation, and disassembly of the spliceosome as it acts on its pre-mRNA substrate remain poorly understood, a challenge that persists for many biomolecular machines. Here, we developed a fluorescence-based Single Molecule Cluster Analysis (SiMCAn) tool to dissect the manifold conformational dynamics of a pre-mRNA through the splicing cycle. By clustering common dynamic behaviors derived from selectively blocked splicing reactions, SiMCAn was able to identify signature conformations and dynamic behaviors of multiple ATP-dependent intermediates. In addition, it identified a conformation adopted late in splicing by a 3′ splice site mutant, invoking a mechanism for substrate proofreading. SiMCAn presents a novel framework for interpreting complex single molecule behaviors that should prove widely useful for the comprehensive analysis of a plethora of dynamic cellular machines. PMID:26414013

  6. Integrating text mining, data mining, and network analysis for identifying genetic breast cancer trends.

    Science.gov (United States)

    Jurca, Gabriela; Addam, Omar; Aksac, Alper; Gao, Shang; Özyer, Tansel; Demetrick, Douglas; Alhajj, Reda

    2016-04-26

    Breast cancer is a serious disease which affects many women and may lead to death. It has received considerable attention from the research community. Thus, biomedical researchers aim to find genetic biomarkers indicative of the disease. Novel biomarkers can be elucidated from the existing literature. However, the vast amount of scientific publications on breast cancer make this a daunting task. This paper presents a framework which investigates existing literature data for informative discoveries. It integrates text mining and social network analysis in order to identify new potential biomarkers for breast cancer. We utilized PubMed for the testing. We investigated gene-gene interactions, as well as novel interactions such as gene-year, gene-country, and abstract-country to find out how the discoveries varied over time and how overlapping/diverse are the discoveries and the interest of various research groups in different countries. Interesting trends have been identified and discussed, e.g., different genes are highlighted in relationship to different countries though the various genes were found to share functionality. Some text analysis based results have been validated against results from other tools that predict gene-gene relations and gene functions.

  7. Mini-DIAL system measurements coupled with multivariate data analysis to identify TIC and TIM simulants: preliminary absorption database analysis.

    Science.gov (United States)

    Gaudio, P.; Malizia, A.; Gelfusa, M.; Martinelli, E.; Di Natale, C.; Poggi, L. A.; Bellecci, C.

    2017-01-01

    Nowadays Toxic Industrial Components (TICs) and Toxic Industrial Materials (TIMs) are one of the most dangerous and diffuse vehicle of contamination in urban and industrial areas. The academic world together with the industrial and military one are working on innovative solutions to monitor the diffusion in atmosphere of such pollutants. In this phase the most common commercial sensors are based on “point detection” technology but it is clear that such instruments cannot satisfy the needs of the smart cities. The new challenge is developing stand-off systems to continuously monitor the atmosphere. Quantum Electronics and Plasma Physics (QEP) research group has a long experience in laser system development and has built two demonstrators based on DIAL (Differential Absorption of Light) technology could be able to identify chemical agents in atmosphere. In this work the authors will present one of those DIAL system, the miniaturized one, together with the preliminary results of an experimental campaign conducted on TICs and TIMs simulants in cell with aim of use the absorption database for the further atmospheric an analysis using the same DIAL system. The experimental results are analysed with standard multivariate data analysis technique as Principal Component Analysis (PCA) to develop a classification model aimed at identifying organic chemical compound in atmosphere. The preliminary results of absorption coefficients of some chemical compound are shown together pre PCA analysis.

  8. Mini-DIAL system measurements coupled with multivariate data analysis to identify TIC and TIM simulants: preliminary absorption database analysis

    International Nuclear Information System (INIS)

    Gaudio, P; Malizia, A; Gelfusa, M; Poggi, L.A.; Martinelli, E.; Di Natale, C.; Bellecci, C.

    2017-01-01

    Nowadays Toxic Industrial Components (TICs) and Toxic Industrial Materials (TIMs) are one of the most dangerous and diffuse vehicle of contamination in urban and industrial areas. The academic world together with the industrial and military one are working on innovative solutions to monitor the diffusion in atmosphere of such pollutants. In this phase the most common commercial sensors are based on “point detection” technology but it is clear that such instruments cannot satisfy the needs of the smart cities. The new challenge is developing stand-off systems to continuously monitor the atmosphere. Quantum Electronics and Plasma Physics (QEP) research group has a long experience in laser system development and has built two demonstrators based on DIAL (Differential Absorption of Light) technology could be able to identify chemical agents in atmosphere. In this work the authors will present one of those DIAL system, the miniaturized one, together with the preliminary results of an experimental campaign conducted on TICs and TIMs simulants in cell with aim of use the absorption database for the further atmospheric an analysis using the same DIAL system. The experimental results are analysed with standard multivariate data analysis technique as Principal Component Analysis (PCA) to develop a classification model aimed at identifying organic chemical compound in atmosphere. The preliminary results of absorption coefficients of some chemical compound are shown together pre PCA analysis. (paper)

  9. A new approach to hazardous materials transportation risk analysis: decision modeling to identify critical variables.

    Science.gov (United States)

    Clark, Renee M; Besterfield-Sacre, Mary E

    2009-03-01

    We take a novel approach to analyzing hazardous materials transportation risk in this research. Previous studies analyzed this risk from an operations research (OR) or quantitative risk assessment (QRA) perspective by minimizing or calculating risk along a transport route. Further, even though the majority of incidents occur when containers are unloaded, the research has not focused on transportation-related activities, including container loading and unloading. In this work, we developed a decision model of a hazardous materials release during unloading using actual data and an exploratory data modeling approach. Previous studies have had a theoretical perspective in terms of identifying and advancing the key variables related to this risk, and there has not been a focus on probability and statistics-based approaches for doing this. Our decision model empirically identifies the critical variables using an exploratory methodology for a large, highly categorical database involving latent class analysis (LCA), loglinear modeling, and Bayesian networking. Our model identified the most influential variables and countermeasures for two consequences of a hazmat incident, dollar loss and release quantity, and is one of the first models to do this. The most influential variables were found to be related to the failure of the container. In addition to analyzing hazmat risk, our methodology can be used to develop data-driven models for strategic decision making in other domains involving risk.

  10. Comparative Transcriptome Analysis Identifies Putative Genes Involved in the Biosynthesis of Xanthanolides in Xanthium strumarium L.

    Directory of Open Access Journals (Sweden)

    Yuanjun Li

    2016-08-01

    Full Text Available Xanthium strumarium L. is a traditional Chinese herb belonging to the Asteraceae family. The major bioactive components of this plant are sesquiterpene lactones, which include the xanthanolides. To date, the biogenesis of xanthanolides, especiallytheir downstream pathway, remains largely unknown. In X. strumarium, xanthanolides primarily accumulate in its glandular trichomes. To identify putative gene candidates involved in the biosynthesis of xanthanolides, three X. strumarium transcriptomes, which were derived from the young leaves of two different cultivars and the purified glandular trichomes from one of the cultivars, were constructed in this study. In total, 157 million clean reads were generated and assembled into 91,861 unigenes, of which 59,858 unigenes were successfully annotated. All the genes coding for known enzymes in the upstream pathway to the biosynthesis of xanthanolides were present in the X. strumarium transcriptomes. From a comparative analysis of the X. strumarium transcriptomes, this study identified a number of gene candidates that are putatively involved in the downstream pathway to the synthesis of xanthanolides, such as four unigenes encoding CYP71 P450s, 50 unigenes for dehydrogenases, and 27 genes for acetyltransferases. The possible functions of these four CYP71 candidates are extensively discussed. In addition, 116 transcription factors that were highly expressed in X. strumarium glandular trichomes were also identified. Their possible regulatory roles in the biosynthesis of sesquiterpene lactones are discussed. The global transcriptomic data for X. strumarium should provide a valuable resource for further research into the biosynthesis of xanthanolides.

  11. Analysis combining correlated glaucoma traits identifies five new risk loci for open-angle glaucoma.

    Science.gov (United States)

    Gharahkhani, Puya; Burdon, Kathryn P; Cooke Bailey, Jessica N; Hewitt, Alex W; Law, Matthew H; Pasquale, Louis R; Kang, Jae H; Haines, Jonathan L; Souzeau, Emmanuelle; Zhou, Tiger; Siggs, Owen M; Landers, John; Awadalla, Mona; Sharma, Shiwani; Mills, Richard A; Ridge, Bronwyn; Lynn, David; Casson, Robert; Graham, Stuart L; Goldberg, Ivan; White, Andrew; Healey, Paul R; Grigg, John; Lawlor, Mitchell; Mitchell, Paul; Ruddle, Jonathan; Coote, Michael; Walland, Mark; Best, Stephen; Vincent, Andrea; Gale, Jesse; RadfordSmith, Graham; Whiteman, David C; Montgomery, Grant W; Martin, Nicholas G; Mackey, David A; Wiggs, Janey L; MacGregor, Stuart; Craig, Jamie E

    2018-02-15

    Open-angle glaucoma (OAG) is a major cause of blindness worldwide. To identify new risk loci for OAG, we performed a genome-wide association study in 3,071 OAG cases and 6,750 unscreened controls, and meta-analysed the results with GWAS data for intraocular pressure (IOP) and optic disc parameters (the overall meta-analysis sample size varying between 32,000 to 48,000 participants), which are glaucoma-related traits. We identified and independently validated four novel genome-wide significant associations within or near MYOF and CYP26A1, LINC02052 and CRYGS, LMX1B, and LMO7 using single variant tests, one additional locus (C9) using gene-based tests, and two genetic pathways - "response to fluid shear stress" and "abnormal retina morphology" - in pathway-based tests. Interestingly, some of the new risk loci contribute to risk of other genetically-correlated eye diseases including myopia and age-related macular degeneration. To our knowledge, this study is the first integrative study to combine genetic data from OAG and its correlated traits to identify new risk variants and genetic pathways, highlighting the future potential of combining genetic data from genetically-correlated eye traits for the purpose of gene discovery and mapping.

  12. Latent class analysis identifies distinct phenotypes of primary graft dysfunction after lung transplantation.

    Science.gov (United States)

    Shah, Rupal J; Diamond, Joshua M; Cantu, Edward; Lee, James C; Lederer, David J; Lama, Vibha N; Orens, Jonathan; Weinacker, Ann; Wilkes, David S; Bhorade, Sangeeta; Wille, Keith M; Ware, Lorraine B; Palmer, Scott M; Crespo, Maria; Localio, A Russell; Demissie, Ejigayehu; Kawut, Steven M; Bellamy, Scarlett L; Christie, Jason D

    2013-08-01

    There is significant heterogeneity within the primary graft dysfunction (PGD) syndrome. We aimed to identify distinct grade 3 PGD phenotypes based on severity of lung dysfunction and patterns of resolution. Subjects from the Lung Transplant Outcomes Group (LTOG) cohort study with grade 3 PGD within 72 h after transplantation were included. Latent class analysis (LCA) was used to statistically identify classes based on changes in PGD International Society for Heart & Lung Transplantation grade over time. Construct validity of the classes was assessed by testing for divergence of recipient, donor, and operative characteristics between classes. Predictive validity was assessed using time to death. Of 1,255 subjects, 361 had grade 3 PGD within the first 72 h after transplantation. LCA identified three distinct phenotypes: (1) severe persistent dysfunction (class 1), (2) complete resolution of dysfunction within 72 h (class 2), and (3) attenuation, without complete resolution within 72 h (class 3). Increased use of cardiopulmonary bypass, greater RBC transfusion, and higher mean pulmonary artery pressure were associated with persistent PGD (class 1). Subjects in class 1 also had the greatest risk of death (hazard ratio, 2.39; 95% CI, 1.57-3.63; P < .001). There are distinct phenotypes of resolution of dysfunction within the severe PGD syndrome. Subjects with early resolution may represent a different mechanism of lung pathology, such as resolving pulmonary edema, whereas those with persistent PGD may represent a more severe phenotype. Future studies aimed at PGD mechanism or treatment may focus on phenotypes based on resolution of graft dysfunction.

  13. Clustering analysis of water distribution systems: identifying critical components and community impacts.

    Science.gov (United States)

    Diao, K; Farmani, R; Fu, G; Astaraie-Imani, M; Ward, S; Butler, D

    2014-01-01

    Large water distribution systems (WDSs) are networks with both topological and behavioural complexity. Thereby, it is usually difficult to identify the key features of the properties of the system, and subsequently all the critical components within the system for a given purpose of design or control. One way is, however, to more explicitly visualize the network structure and interactions between components by dividing a WDS into a number of clusters (subsystems). Accordingly, this paper introduces a clustering strategy that decomposes WDSs into clusters with stronger internal connections than external connections. The detected cluster layout is very similar to the community structure of the served urban area. As WDSs may expand along with urban development in a community-by-community manner, the correspondingly formed distribution clusters may reveal some crucial configurations of WDSs. For verification, the method is applied to identify all the critical links during firefighting for the vulnerability analysis of a real-world WDS. Moreover, both the most critical pipes and clusters are addressed, given the consequences of pipe failure. Compared with the enumeration method, the method used in this study identifies the same group of the most critical components, and provides similar criticality prioritizations of them in a more computationally efficient time.

  14. Identifying the oil price-macroeconomy relationship. An empirical mode decomposition analysis of US data

    International Nuclear Information System (INIS)

    Oladosu, Gbadebo

    2009-01-01

    This paper employs the empirical mode decomposition (EMD) method to filter cyclical components of US quarterly gross domestic product (GDP) and quarterly average oil price (West Texas Intermediate - WTI). The method is adaptive and applicable to non-linear and non-stationary data. A correlation analysis of the resulting components is performed and examined for insights into the relationship between oil and the economy. Several components of this relationship are identified. However, the principal one is that the medium-run component of the oil price has a negative relationship with the main cyclical component of the GDP. In addition, weak correlations suggesting a lagging, demand-driven component and a long-run component of the relationship were also identified. Comparisons of these findings with significant oil supply disruption and recession dates were supportive. The study identifies a number of lessons applicable to recent oil market events, including the eventuality of persistent oil price and economic decline following a long oil price run-up. In addition, it was found that oil market related exogenous events are associated with short- to medium-run price implications regardless of whether they lead to actual supply losses. (author)

  15. Genome-wide association scan meta-analysis identifies three Loci influencing adiposity and fat distribution.

    Directory of Open Access Journals (Sweden)

    Cecilia M Lindgren

    2009-06-01

    Full Text Available To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580 informative for adult waist circumference (WC and waist-hip ratio (WHR. We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9x10(-11 and MSRA (WC, P = 8.9x10(-9. A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6x10(-8. The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity.

  16. Genome-Wide Association Scan Meta-Analysis Identifies Three Loci Influencing Adiposity and Fat Distribution

    Science.gov (United States)

    Qi, Lu; Speliotes, Elizabeth K.; Thorleifsson, Gudmar; Willer, Cristen J.; Herrera, Blanca M.; Jackson, Anne U.; Lim, Noha; Scheet, Paul; Soranzo, Nicole; Amin, Najaf; Aulchenko, Yurii S.; Chambers, John C.; Drong, Alexander; Luan, Jian'an; Lyon, Helen N.; Rivadeneira, Fernando; Sanna, Serena; Timpson, Nicholas J.; Zillikens, M. Carola; Zhao, Jing Hua; Almgren, Peter; Bandinelli, Stefania; Bennett, Amanda J.; Bergman, Richard N.; Bonnycastle, Lori L.; Bumpstead, Suzannah J.; Chanock, Stephen J.; Cherkas, Lynn; Chines, Peter; Coin, Lachlan; Cooper, Cyrus; Crawford, Gabriel; Doering, Angela; Dominiczak, Anna; Doney, Alex S. F.; Ebrahim, Shah; Elliott, Paul; Erdos, Michael R.; Estrada, Karol; Ferrucci, Luigi; Fischer, Guido; Forouhi, Nita G.; Gieger, Christian; Grallert, Harald; Groves, Christopher J.; Grundy, Scott; Guiducci, Candace; Hadley, David; Hamsten, Anders; Havulinna, Aki S.; Hofman, Albert; Holle, Rolf; Holloway, John W.; Illig, Thomas; Isomaa, Bo; Jacobs, Leonie C.; Jameson, Karen; Jousilahti, Pekka; Karpe, Fredrik; Kuusisto, Johanna; Laitinen, Jaana; Lathrop, G. Mark; Lawlor, Debbie A.; Mangino, Massimo; McArdle, Wendy L.; Meitinger, Thomas; Morken, Mario A.; Morris, Andrew P.; Munroe, Patricia; Narisu, Narisu; Nordström, Anna; Nordström, Peter; Oostra, Ben A.; Palmer, Colin N. A.; Payne, Felicity; Peden, John F.; Prokopenko, Inga; Renström, Frida; Ruokonen, Aimo; Salomaa, Veikko; Sandhu, Manjinder S.; Scott, Laura J.; Scuteri, Angelo; Silander, Kaisa; Song, Kijoung; Yuan, Xin; Stringham, Heather M.; Swift, Amy J.; Tuomi, Tiinamaija; Uda, Manuela; Vollenweider, Peter; Waeber, Gerard; Wallace, Chris; Walters, G. Bragi; Weedon, Michael N.; Witteman, Jacqueline C. M.; Zhang, Cuilin; Zhang, Weihua; Caulfield, Mark J.; Collins, Francis S.; Davey Smith, George; Day, Ian N. M.; Franks, Paul W.; Hattersley, Andrew T.; Hu, Frank B.; Jarvelin, Marjo-Riitta; Kong, Augustine; Kooner, Jaspal S.; Laakso, Markku; Lakatta, Edward; Mooser, Vincent; Morris, Andrew D.; Peltonen, Leena; Samani, Nilesh J.; Spector, Timothy D.; Strachan, David P.; Tanaka, Toshiko; Tuomilehto, Jaakko; Uitterlinden, André G.; van Duijn, Cornelia M.; Wareham, Nicholas J.; Watkins for the PROCARDIS consortia, Hugh; Waterworth, Dawn M.; Boehnke, Michael; Deloukas, Panos; Groop, Leif; Hunter, David J.; Thorsteinsdottir, Unnur; Schlessinger, David; Wichmann, H.-Erich; Frayling, Timothy M.; Abecasis, Gonçalo R.; Hirschhorn, Joel N.; Loos, Ruth J. F.; Stefansson, Kari; Mohlke, Karen L.; Barroso, Inês; McCarthy for the GIANT consortium, Mark I.

    2009-01-01

    To identify genetic loci influencing central obesity and fat distribution, we performed a meta-analysis of 16 genome-wide association studies (GWAS, N = 38,580) informative for adult waist circumference (WC) and waist–hip ratio (WHR). We selected 26 SNPs for follow-up, for which the evidence of association with measures of central adiposity (WC and/or WHR) was strong and disproportionate to that for overall adiposity or height. Follow-up studies in a maximum of 70,689 individuals identified two loci strongly associated with measures of central adiposity; these map near TFAP2B (WC, P = 1.9×10−11) and MSRA (WC, P = 8.9×10−9). A third locus, near LYPLAL1, was associated with WHR in women only (P = 2.6×10−8). The variants near TFAP2B appear to influence central adiposity through an effect on overall obesity/fat-mass, whereas LYPLAL1 displays a strong female-only association with fat distribution. By focusing on anthropometric measures of central obesity and fat distribution, we have identified three loci implicated in the regulation of human adiposity. PMID:19557161

  17. Root Source Analysis/ValuStream[Trade Mark] - A Methodology for Identifying and Managing Risks

    Science.gov (United States)

    Brown, Richard Lee

    2008-01-01

    Root Source Analysis (RoSA) is a systems engineering methodology that has been developed at NASA over the past five years. It is designed to reduce costs, schedule, and technical risks by systematically examining critical assumptions and the state of the knowledge needed to bring to fruition the products that satisfy mission-driven requirements, as defined for each element of the Work (or Product) Breakdown Structure (WBS or PBS). This methodology is sometimes referred to as the ValuStream method, as inherent in the process is the linking and prioritizing of uncertainties arising from knowledge shortfalls directly to the customer's mission driven requirements. RoSA and ValuStream are synonymous terms. RoSA is not simply an alternate or improved method for identifying risks. It represents a paradigm shift. The emphasis is placed on identifying very specific knowledge shortfalls and assumptions that are the root sources of the risk (the why), rather than on assessing the WBS product(s) themselves (the what). In so doing RoSA looks forward to anticipate, identify, and prioritize knowledge shortfalls and assumptions that are likely to create significant uncertainties/ risks (as compared to Root Cause Analysis, which is most often used to look back to discover what was not known, or was assumed, that caused the failure). Experience indicates that RoSA, with its primary focus on assumptions and the state of the underlying knowledge needed to define, design, build, verify, and operate the products, can identify critical risks that historically have been missed by the usual approaches (i.e., design review process and classical risk identification methods). Further, the methodology answers four critical questions for decision makers and risk managers: 1. What s been included? 2. What's been left out? 3. How has it been validated? 4. Has the real source of the uncertainty/ risk been identified, i.e., is the perceived problem the real problem? Users of the RoSA methodology

  18. Using EMMA and MIX analysis to assess mixing ratios and to identify hydrochemical reactions in groundwater.

    Science.gov (United States)

    Tubau, Isabel; Vàzquez-Suñé, Enric; Jurado, Anna; Carrera, Jesús

    2014-02-01

    This study presents a methodology using an end-member mixing analysis (EMMA) and MIX to compute mixing ratios and to identify hydrochemical reactions in groundwater. The methodology consists of (1) identifying the potential sources of recharge, (2) characterising recharge sources and mixed water samples using hydrogeochemistry, (3) selecting chemical species to be used in the analysis and (4) calculating mixing ratios and identification of hydrochemical reactions in groundwater. This approach has been applied in the Besòs River Delta area, where we have collected 51 groundwater samples and a long data register of the hydrogeochemistry of the Besòs River created by the Catalan Water Agency is also available. The EMMA performed in the Besòs River suggests that 3 end-members are required to explain its temporal variability, accounting for the species chloride, sulphate, sodium, bicarbonate, calcium, magnesium, potassium, ammonium, total nitrogen, and electrical conductivity. One river end-member is from the wet periods (W1), and two are from dry periods (D1 and D2). These end-members have been used to compute mixing ratios in groundwater samples because the Besòs River is considered the main recharge source for the aquifer. Overall, dry season end-members dominated over the wet season end-member, in a proportion of 4:1. Moreover, when departures from the mixing line exist, geochemical processes might be identified. Redox processes, carbonate dissolution/precipitation and ion exchange processes may occur in Besòs Delta aquifer. Copyright © 2013 Elsevier B.V. All rights reserved.

  19. Feature selection and classification for microarray data analysis: Evolutionary methods for identifying predictive genes

    Directory of Open Access Journals (Sweden)

    Aitken Stuart

    2005-06-01

    Full Text Available Abstract Background In the clinical context, samples assayed by microarray are often classified by cell line or tumour type and it is of interest to discover a set of genes that can be used as class predictors. The leukemia dataset of Golub et al. 1 and the NCI60 dataset of Ross et al. 2 present multiclass classification problems where three tumour types and nine cell lines respectively must be identified. We apply an evolutionary algorithm to identify the near-optimal set of predictive genes that classify the data. We also examine the initial gene selection step whereby the most informative genes are selected from the genes assayed. Results In the absence of feature selection, classification accuracy on the training data is typically good, but not replicated on the testing data. Gene selection using the RankGene software 3 is shown to significantly improve performance on the testing data. Further, we show that the choice of feature selection criteria can have a significant effect on accuracy. The evolutionary algorithm is shown to perform stably across the space of possible parameter settings – indicating the robustness of the approach. We assess performance using a low variance estimation technique, and present an analysis of the genes most often selected as predictors. Conclusion The computational methods we have developed perform robustly and accurately, and yield results in accord with clinical knowledge: A Z-score analysis of the genes most frequently selected identifies genes known to discriminate AML and Pre-T ALL leukemia. This study also confirms that significantly different sets of genes are found to be most discriminatory as the sample classes are refined.

  20. Depressive subtypes in an elderly cohort identified using latent class analysis.

    Science.gov (United States)

    Veltman, E M; Lamers, F; Comijs, H C; de Waal, M W M; Stek, M L; van der Mast, R C; Rhebergen, D

    2017-08-15

    Clinical findings indicate heterogeneity of depressive disorders, stressing the importance of subtyping depression for research and clinical care. Subtypes of the common late life depression are however seldom studied. Data-driven methods may help provide a more empirically-based classification of late-life depression. Data were used from the Netherlands Study of Depression in Older People (NESDO) derived from 359 persons, aged 60 years or older, with a current diagnosis of major depressive disorder. Latent class analysis (LCA) was used to identify subtypes of depression, using ten CIDI-based depression items. Classes were then characterized using various sociodemographic and clinical characteristics. The most prevalent class, as identified by LCA, was a moderate-severe class (prevalence 46.5%), followed by a severe melancholic class (prevalence 38.4%), and a severe atypical class (prevalence 15.0%). The strongest distinguishing features between the three classes were appetite and weight and, to a lesser extent, psychomotor symptoms and loss of interest. Compared with the melancholic class, the severe atypical class had the highest prevalence of females, the lowest mean age, the highest BMI, and highest prevalence of both cardiovascular disease, and metabolic syndrome. The strongest distinguishing symptoms, appetite and weight, could be correlated. Further, only longitudinal studies could demonstrate whether the identified classes are stable on the long term. In older persons with depressive disorders, three distinct subtypes were identified, similar to subtypes found in younger adults. The strongest distinguishing features were appetite and weight; moreover, classes differed strongly on prevalence of metabolic syndrome and cardiovascular disease. These findings suggest differences in the involvement of metabolic pathways across classes, which should be considered when investigating the pathogenesis and (eventually) treatment of depression in older persons

  1. Identifying Factors That Predict Worse Constipation Symptoms in Palliative Care Patients: A Secondary Analysis.

    Science.gov (United States)

    Clark, Katherine; Lam, Lawrence T; Talley, Nicholas J; Phillips, Jane L; Currow, David C

    2017-05-01

    The aim of this work was to investigate whether variables identified as likely to impact the experience of constipation in other clinical settings similarly affected the experiences of constipated palliative care patients. The majority of palliative care patients with cancer are likely to be bothered by constipation symptoms at some point in their disease trajectory. Despite this, it remains unclear as to which factors predict more severe problems. This study was conducted in a sample of 94 constipated palliative care patients who were asked to voluntarily complete a series of questions regarding their demographic and other characteristics, including whether they had chronic constipation symptoms, that is, constipation symptoms for 12 months. Other variables included age, body mass index, sex, performance status, and regular opioids and their doses. At the same time, they were asked to complete the Patient Assessment of Constipation Symptoms (PAC-SYM) and Patient Assessment of Constipation Quality of Life (PAC-QOL) questionnaires. Descriptive statistics summarized baseline data. Unadjusted associations between the selected variables on PAC-SYM were examined by using bi-variate analyses. Significant variables identified on bi-variate analyses were included in a multivariate analysis. The final results identified that only the chronicity of constipation symptoms predicted more severe symptoms. This relationship persisted when this single variable was retained in the final model, illustrating that PAC-SYM scores are 0.41 higher in patients with chronic constipation compared with those without it (p = 0.02). In contrast, regular opioid use was not identified as a significant factor (p = 0.56). This study suggests that the factor most likely to predict worse constipation symptoms was the duration that people had experienced problems. Further, those who perceived their constipation symptoms to be more severe had a poorer quality of life. More work is required to

  2. Genome-wide pathway analysis identifies VEGF pathway association with oral ulceration in systemic lupus erythematosus.

    Science.gov (United States)

    Aterido, Adrià; Julià, Antonio; Carreira, Patricia; Blanco, Ricardo; López-Longo, José Javier; Venegas, José Javier Pérez; Olivé, Àlex; Andreu, José Luís; Aguirre-Zamorano, Maria Ángeles; Vela, Paloma; Nolla, Joan M; Marenco-de la Fuente, José Luís; Zea, Antonio; Pego, José María; Freire, Mercedes; Díez, Elvira; López-Lasanta, María; López-Corbeto, Mireia; Palau, Núria; Tortosa, Raül; Gelpí, Josep Lluís; Absher, Devin; Myers, Richard M; Fernández-Nebro, Antonio; Marsal, Sara

    2017-06-15

    Systemic lupus erythematosus (SLE) is a genetically complex rheumatic disease characterized by heterogeneous clinical manifestations of unknown etiology. Recent studies have suggested the existence of a genetic basis for SLE heterogeneity. The objective of the present study was to identify new genetic variation associated with the clinically relevant phenotypes in SLE. A two-stage pathway-based approach was used to identify the genetic variation associated with the main clinical phenotypes in SLE. In the discovery stage, 482 SLE patients were genotyped using Illumina Human Quad610 microarrays. Association between 798 reference genetic pathways from the Molecular Signatures Database and 11 SLE phenotypes was tested using the set-based method implemented in PLINK software. Pathways significantly associated after multiple test correction were subsequently tested for replication in an independent cohort of 425 SLE patients. Using an in silico approach, we analyzed the functional effects of common SLE therapies on the replicated genetic pathways. The association of known SLE risk variants with the development of the clinical phenotypes was also analyzed. In the discovery stage, we found a significant association between the vascular endothelial growth factor (VEGF) pathway and oral ulceration (P value for false discovery rate (P FDR ) oral ulceration. Therapies commonly used to treat mucocutaneous phenotypes in SLE were found to strongly influence VEGF pathway gene expression (P = 4.60e-4 to 5.38e-14). Analysis of known SLE risk loci identified a strong association between PTPN22 and the risk of hematologic disorder and with the development of antinuclear antibodies. The present study has identified VEGF genetic pathway association with the risk of oral ulceration in SLE. New therapies targeting the VEGF pathway could be more effective in reducing the severity of this phenotype. These findings represent a first step towards the understanding of the genetic basis

  3. Transcriptomic analysis using olive varieties and breeding progenies identify candidate genes involved in plant architecture

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    Juan José eGonzález Plaza

    2016-03-01

    Full Text Available Plant architecture is a critical trait in fruit crops that can significantly influence yield, pruning, planting density and harvesting. Little is known about how plant architecture is genetically determined in olive, were most of the existing varieties are traditional with an architecture poorly suited for modern growing and harvesting systems. In the present study, we have carried out microarray analysis of meristematic tissue to compare expression profiles of olive varieties displaying differences in architecture, as well as seedlings from their cross pooled on the basis of their sharing architecture-related phenotypes. The microarray used, previously developed by our group has already been applied to identify candidates genes involved in regulating juvenile to adult transition in the shoot apex of seedlings. Varieties with distinct architecture phenotypes and individuals from segregating progenies displaying opposite architecture features were used to link phenotype to expression. Here, we identify 2,252 differentially expressed genes associated to differences in plant architecture. Microarray results were validated by quantitative RT-PCR carried out on genes with functional annotation likely related to plant architecture. Twelve of these genes were further analyzed in individual seedlings of the corresponding pool. We also examined Arabidopsis mutants in putative orthologs of these targeted candidate genes, finding altered architecture for most of them. This supports a functional conservation between species and potential biological relevance of the candidate genes identified. This study is the first to identify genes associated to plant architecture in olive, and the results obtained could be of great help in future programs aimed at selecting phenotypes adapted to modern cultivation practices in this species.

  4. Transcriptomic Analysis Using Olive Varieties and Breeding Progenies Identifies Candidate Genes Involved in Plant Architecture.

    Science.gov (United States)

    González-Plaza, Juan J; Ortiz-Martín, Inmaculada; Muñoz-Mérida, Antonio; García-López, Carmen; Sánchez-Sevilla, José F; Luque, Francisco; Trelles, Oswaldo; Bejarano, Eduardo R; De La Rosa, Raúl; Valpuesta, Victoriano; Beuzón, Carmen R

    2016-01-01

    Plant architecture is a critical trait in fruit crops that can significantly influence yield, pruning, planting density and harvesting. Little is known about how plant architecture is genetically determined in olive, were most of the existing varieties are traditional with an architecture poorly suited for modern growing and harvesting systems. In the present study, we have carried out microarray analysis of meristematic tissue to compare expression profiles of olive varieties displaying differences in architecture, as well as seedlings from their cross pooled on the basis of their sharing architecture-related phenotypes. The microarray used, previously developed by our group has already been applied to identify candidates genes involved in regulating juvenile to adult transition in the shoot apex of seedlings. Varieties with distinct architecture phenotypes and individuals from segregating progenies displaying opposite architecture features were used to link phenotype to expression. Here, we identify 2252 differentially expressed genes (DEGs) associated to differences in plant architecture. Microarray results were validated by quantitative RT-PCR carried out on genes with functional annotation likely related to plant architecture. Twelve of these genes were further analyzed in individual seedlings of the corresponding pool. We also examined Arabidopsis mutants in putative orthologs of these targeted candidate genes, finding altered architecture for most of them. This supports a functional conservation between species and potential biological relevance of the candidate genes identified. This study is the first to identify genes associated to plant architecture in olive, and the results obtained could be of great help in future programs aimed at selecting phenotypes adapted to modern cultivation practices in this species.

  5. Integrated analysis of multiple microarray datasets identifies a reproducible survival predictor in ovarian cancer.

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    Panagiotis A Konstantinopoulos

    Full Text Available BACKGROUND: Public data integration may help overcome challenges in clinical implementation of microarray profiles. We integrated several ovarian cancer datasets to identify a reproducible predictor of survival. METHODOLOGY/PRINCIPAL FINDINGS: Four microarray datasets from different institutions comprising 265 advanced stage tumors were uniformly reprocessed into a single training dataset, also adjusting for inter-laboratory variation ("batch-effect". Supervised principal component survival analysis was employed to identify prognostic models. Models were independently validated in a 61-patient cohort using a custom array genechip and a publicly available 229-array dataset. Molecular correspondence of high- and low-risk outcome groups between training and validation datasets was demonstrated using Subclass Mapping. Previously established molecular phenotypes in the 2(nd validation set were correlated with high and low-risk outcome groups. Functional representational and pathway analysis was used to explore gene networks associated with high and low risk phenotypes. A 19-gene model showed optimal performance in the training set (median OS 31 and 78 months, p < 0.01, 1(st validation set (median OS 32 months versus not-yet-reached, p = 0.026 and 2(nd validation set (median OS 43 versus 61 months, p = 0.013 maintaining independent prognostic power in multivariate analysis. There was strong molecular correspondence of the respective high- and low-risk tumors between training and 1(st validation set. Low and high-risk tumors were enriched for favorable and unfavorable molecular subtypes and pathways, previously defined in the public 2(nd validation set. CONCLUSIONS/SIGNIFICANCE: Integration of previously generated cancer microarray datasets may lead to robust and widely applicable survival predictors. These predictors are not simply a compilation of prognostic genes but appear to track true molecular phenotypes of good- and poor-outcome.

  6. Utilizing a Photo-Analysis Software for Content Identifying Method (CIM

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    Nejad Nasim Sahraei

    2015-01-01

    Full Text Available Content Identifying Methodology or (CIM was developed to measure public preferences in order to reveal the common characteristics of landscapes and aspects of underlying perceptions including the individual's reactions to content and spatial configuration, therefore, it can assist with the identification of factors that influenced preference. Regarding the analysis of landscape photographs through CIM, there are several studies utilizing image analysis software, such as Adobe Photoshop, in order to identify the physical contents in the scenes. This study attempts to evaluate public’s ‘preferences for aesthetic qualities of pedestrian bridges in urban areas through a photo-questionnaire survey, in which respondents evaluated images of pedestrian bridges in urban areas. Two groups of images were evaluated as the most and least preferred scenes that concern the highest and lowest mean scores respectively. These two groups were analyzed by CIM and also evaluated based on the respondent’s description of each group to reveal the pattern of preferences and the factors that may affect them. Digimizer Software was employed to triangulate the two approaches and to determine the role of these factors on people’s preferences. This study attempts to introduce the useful software for image analysis which can measure the physical contents and also their spatial organization in the scenes. According to the findings, it is revealed that Digimizer could be a useful tool in CIM approaches through preference studies that utilizes photographs in place of the actual landscape in order to determine the most important factors in public preferences for pedestrian bridges in urban areas.

  7. Evolution of a Pathogen: A Comparative Genomics Analysis Identifies a Genetic Pathway to Pathogenesis in Acinetobacter

    Science.gov (United States)

    Sahl, Jason W.; Gillece, John D.; Schupp, James M.; Waddell, Victor G.; Driebe, Elizabeth M.; Engelthaler, David M.; Keim, Paul

    2013-01-01

    Acinetobacter baumannii is an emergent and global nosocomial pathogen. In addition to A. baumannii, other Acinetobacter species, especially those in the Acinetobacter calcoaceticus-baumannii (Acb) complex, have also been associated with serious human infection. Although mechanisms of attachment, persistence on abiotic surfaces, and pathogenesis in A. baumannii have been identified, the genetic mechanisms that explain the emergence of A. baumannii as the most widespread and virulent Acinetobacter species are not fully understood. Recent whole genome sequencing has provided insight into the phylogenetic structure of the genus Acinetobacter. However, a global comparison of genomic features between Acinetobacter spp. has not been described in the literature. In this study, 136 Acinetobacter genomes, including 67 sequenced in this study, were compared to identify the acquisition and loss of genes in the expansion of the Acinetobacter genus. A whole genome phylogeny confirmed that A. baumannii is a monophyletic clade and that the larger Acb complex is also a well-supported monophyletic group. The whole genome phylogeny provided the framework for a global genomic comparison based on a blast score ratio (BSR) analysis. The BSR analysis demonstrated that specific genes have been both lost and acquired in the evolution of A. baumannii. In addition, several genes associated with A. baumannii pathogenesis were found to be more conserved in the Acb complex, and especially in A. baumannii, than in other Acinetobacter genomes; until recently, a global analysis of the distribution and conservation of virulence factors across the genus was not possible. The results demonstrate that the acquisition of specific virulence factors has likely contributed to the widespread persistence and virulence of A. baumannii. The identification of novel features associated with transcriptional regulation and acquired by clades in the Acb complex presents targets for better understanding the

  8. Cross-study analysis of gene expression data for intermediate neuroblastoma identifies two biological subtypes

    International Nuclear Information System (INIS)

    Warnat, Patrick; Oberthuer, André; Fischer, Matthias; Westermann, Frank; Eils, Roland; Brors, Benedikt

    2007-01-01

    Neuroblastoma patients show heterogeneous clinical courses ranging from life-threatening progression to spontaneous regression. Recently, gene expression profiles of neuroblastoma tumours were associated with clinically different phenotypes. However, such data is still rare for important patient subgroups, such as patients with MYCN non-amplified advanced stage disease. Prediction of the individual course of disease and optimal therapy selection in this cohort is challenging. Additional research effort is needed to describe the patterns of gene expression in this cohort and to identify reliable prognostic markers for this subset of patients. We combined gene expression data from two studies in a meta-analysis in order to investigate differences in gene expression of advanced stage (3 or 4) tumours without MYCN amplification that show contrasting outcomes (alive or dead) at five years after initial diagnosis. In addition, a predictive model for outcome was generated. Gene expression profiles from 66 patients were included from two studies using different microarray platforms. In the combined data set, 72 genes were identified as differentially expressed by meta-analysis at a false discovery rate (FDR) of 8.33%. Meta-analysis detected 34 differentially expressed genes that were not found as significant in either single study. Outcome prediction based on data of both studies resulted in a predictive accuracy of 77%. Moreover, the genes that were differentially expressed in subgroups of advanced stage patients without MYCN amplification accurately separated MYCN amplified tumours from low stage tumours without MYCN amplification. Our findings support the hypothesis that neuroblastoma consists of two biologically distinct subgroups that differ by characteristic gene expression patterns, which are associated with divergent clinical outcome

  9. Evolution of a pathogen: a comparative genomics analysis identifies a genetic pathway to pathogenesis in Acinetobacter.

    Directory of Open Access Journals (Sweden)

    Jason W Sahl

    Full Text Available Acinetobacter baumannii is an emergent and global nosocomial pathogen. In addition to A. baumannii, other Acinetobacter species, especially those in the Acinetobacter calcoaceticus-baumannii (Acb complex, have also been associated with serious human infection. Although mechanisms of attachment, persistence on abiotic surfaces, and pathogenesis in A. baumannii have been identified, the genetic mechanisms that explain the emergence of A. baumannii as the most widespread and virulent Acinetobacter species are not fully understood. Recent whole genome sequencing has provided insight into the phylogenetic structure of the genus Acinetobacter. However, a global comparison of genomic features between Acinetobacter spp. has not been described in the literature. In this study, 136 Acinetobacter genomes, including 67 sequenced in this study, were compared to identify the acquisition and loss of genes in the expansion of the Acinetobacter genus. A whole genome phylogeny confirmed that A. baumannii is a monophyletic clade and that the larger Acb complex is also a well-supported monophyletic group. The whole genome phylogeny provided the framework for a global genomic comparison based on a blast score ratio (BSR analysis. The BSR analysis demonstrated that specific genes have been both lost and acquired in the evolution of A. baumannii. In addition, several genes associated with A. baumannii pathogenesis were found to be more conserved in the Acb complex, and especially in A. baumannii, than in other Acinetobacter genomes; until recently, a global analysis of the distribution and conservation of virulence factors across the genus was not possible. The results demonstrate that the acquisition of specific virulence factors has likely contributed to the widespread persistence and virulence of A. baumannii. The identification of novel features associated with transcriptional regulation and acquired by clades in the Acb complex presents targets for better

  10. Can Link Analysis Be Applied to Identify Behavioral Patterns in Train Recorder Data?

    Science.gov (United States)

    Strathie, Ailsa; Walker, Guy H

    2016-03-01

    A proof-of-concept analysis was conducted to establish whether link analysis could be applied to data from on-train recorders to detect patterns of behavior that could act as leading indicators of potential safety issues. On-train data recorders capture data about driving behavior on thousands of routine journeys every day and offer a source of untapped data that could be used to offer insights into human behavior. Data from 17 journeys undertaken by six drivers on the same route over a 16-hr period were analyzed using link analysis, and four key metrics were examined: number of links, network density, diameter, and sociometric status. The results established that link analysis can be usefully applied to data captured from on-vehicle recorders. The four metrics revealed key differences in normal driver behavior. These differences have promising construct validity as leading indicators. Link analysis is one method that could be usefully applied to exploit data routinely gathered by on-vehicle data recorders. It facilitates a proactive approach to safety based on leading indicators, offers a clearer understanding of what constitutes normal driving behavior, and identifies trends at the interface of people and systems, which is currently a key area of strategic risk. These research findings have direct applications in the field of transport data monitoring. They offer a means of automatically detecting patterns in driver behavior that could act as leading indicators of problems during operation and that could be used in the proactive monitoring of driver competence, risk management, and even infrastructure design. © 2015, Human Factors and Ergonomics Society.

  11. SPM: Scanning positron microscope

    Directory of Open Access Journals (Sweden)

    Marcel Dickmann

    2015-08-01

    Full Text Available The Munich scanning positron microscope, operated by the Universität der Bundeswehr München and the Technische Universität München, located at NEPOMUC, permits positron lifetime measurements with a lateral resolution in the µm range and within an energy range of 1 – 20 keV.

  12. Silicon photomultiplier (SPM) detection of low-level bioluminescence for the development of deployable whole-cell biosensors: possibilities and limitations.

    Science.gov (United States)

    Li, Huaqing; Lopes, Nicholas; Moser, Scott; Sayler, Gary; Ripp, Steven

    2012-03-15

    Whole-cell bacterial bioreporters await miniaturized photon counting modules with high sensitivity and robust compatible hardware to fulfill their promise of versatile, on-site biosensor functionality. In this study, we explore the photon counting readout properties of the silicon photomultiplier (SPM) with a thermoelectric cooler and the possibilities of detecting low-level bioluminescent signals. Detection performance was evaluated through a simulated LED light source and the bioluminescence produced by the genetically engineered Pseudomonas fluorescens bacterial bioreporter 5RL. Compared with the conventional photomultiplier tube (PMT), the results revealed that the cooled SPM exhibits a wider linear response to inducible substrate concentrations (salicylate) ranging from 250 to 5000 ppb. Although cooling of the SPM lowered dark count rates and improved the minimum detectable signal, and the application of a digital filter enhanced the signal-to-noise ratio, the detection of very low light signals is still limited and remains a challenge in the design of compact photon counting systems. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Dipeptide frequency/bias analysis identifies conserved sites of nonrandomness shared by cysteine-rich motifs.

    Science.gov (United States)

    Campion, S R; Ameen, A S; Lai, L; King, J M; Munzenmaier, T N

    2001-08-15

    This report describes the application of a simple computational tool, AAPAIR.TAB, for the systematic analysis of the cysteine-rich EGF, Sushi, and Laminin motif/sequence families at the two-amino acid level. Automated dipeptide frequency/bias analysis detects preferences in the distribution of amino acids in established protein families, by determining which "ordered dipeptides" occur most frequently in comprehensive motif-specific sequence data sets. Graphic display of the dipeptide frequency/bias data revealed family-specific preferences for certain dipeptides, but more importantly detected a shared preference for employment of the ordered dipeptides Gly-Tyr (GY) and Gly-Phe (GF) in all three protein families. The dipeptide Asn-Gly (NG) also exhibited high-frequency and bias in the EGF and Sushi motif families, whereas Asn-Thr (NT) was distinguished in the Laminin family. Evaluation of the distribution of dipeptides identified by frequency/bias analysis subsequently revealed the highly restricted localization of the G(F/Y) and N(G/T) sequence elements at two separate sites of extreme conservation in the consensus sequence of all three sequence families. The similar employment of the high-frequency/bias dipeptides in three distinct protein sequence families was further correlated with the concurrence of these shared molecular determinants at similar positions within the distinctive scaffolds of three structurally divergent, but similarly employed, motif modules.

  14. Dynamics and causalities of atmospheric and oceanic data identified by complex networks and Granger causality analysis

    Science.gov (United States)

    Charakopoulos, A. K.; Katsouli, G. A.; Karakasidis, T. E.

    2018-04-01

    Understanding the underlying processes and extracting detailed characteristics of spatiotemporal dynamics of ocean and atmosphere as well as their interaction is of significant interest and has not been well thoroughly established. The purpose of this study was to examine the performance of two main additional methodologies for the identification of spatiotemporal underlying dynamic characteristics and patterns among atmospheric and oceanic variables from Seawatch buoys from Aegean and Ionian Sea, provided by the Hellenic Center for Marine Research (HCMR). The first approach involves the estimation of cross correlation analysis in an attempt to investigate time-lagged relationships, and further in order to identify the direction of interactions between the variables we performed the Granger causality method. According to the second approach the time series are converted into complex networks and then the main topological network properties such as degree distribution, average path length, diameter, modularity and clustering coefficient are evaluated. Our results show that the proposed analysis of complex network analysis of time series can lead to the extraction of hidden spatiotemporal characteristics. Also our findings indicate high level of positive and negative correlations and causalities among variables, both from the same buoy and also between buoys from different stations, which cannot be determined from the use of simple statistical measures.

  15. Cytokeratin Profiles Identify Diagnostic Signatures in Colorectal Cancer Using Multiplex Analysis of Tissue Microarrays

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    Thomas Knösel

    2006-01-01

    Full Text Available Background and aims: Recent cDNA expression profiling analyses indicate that within specific organ cancers Cytokeratins (CKs dysregulation may identify subgroups with distinct biological phenotypes. Our objectives in this study were (1 to test whether cytokeratins were also distinct on the protein level, (2 to evaluate these biomarkers in a series of well-characterised CRCs, (3 to apply hierarchical cluster analysis to immunohistochemical data. Methods: Tissue microarrays (TMA comprising 468 CRC specimens from 203 patients were constructed to evaluate CK5, CK7, CK8, CK13, CK14, CK16, CK17, CK18, CK19 and CK20. In total, 2919 samples were analyzed. Results: Unsupervised hierarchical clustering discovered subgroups represented by reduced CK8 and CK20 expression, that differed by a shorter patients survival. The evaluation of the specific biomarkers by Kaplan–Meier analysis showed that reduced CK8 expression (p < 0.01 was significantly associated with shorter patients’ survival, but was not an independent factor correlated with tumour stage (pT, grading (G and nodal stage (pN. Conclusions: Reduced coexpression of CK8 and CK20 may indicate an epithelial-mesenchymal transition (EMT representing an important step in the development of more aggressive CRCs. In addition, multiplex analysis of TMAs together with immunohistochemistry (IHC supplemented by hierarchical clustering are a useful, promising and very powerful tool for the identification of tumour subgroups with diagnostic and prognostic signatures.

  16. Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate

    Directory of Open Access Journals (Sweden)

    Zvelebil Marketa

    2008-12-01

    Full Text Available Abstract Background Understanding the molecular control of cell lineages and fate determination in complex tissues is key to not only understanding the developmental biology and cellular homeostasis of such tissues but also for our understanding and interpretation of the molecular pathology of diseases such as cancer. The prerequisite for such an understanding is detailed knowledge of the cell types that make up such tissues, including their comprehensive molecular characterisation. In the mammary epithelium, the bulk of the tissue is composed of three cell lineages, namely the basal/myoepithelial, luminal epithelial estrogen receptor positive and luminal epithelial estrogen receptor negative cells. However, a detailed molecular characterisation of the transcriptomic differences between these three populations has not been carried out. Results A whole transcriptome analysis of basal/myoepithelial cells, luminal estrogen receptor negative cells and luminal estrogen receptor positive cells isolated from the virgin mouse mammary epithelium identified 861, 326 and 488 genes as highly differentially expressed in the three cell types, respectively. Network analysis of the transcriptomic data identified a subpopulation of luminal estrogen receptor negative cells with a novel potential role as non-professional immune cells. Analysis of the data for potential paracrine interacting factors showed that the basal/myoepithelial cells, remarkably, expressed over twice as many ligands and cell surface receptors as the other two populations combined. A number of transcriptional regulators were also identified that were differentially expressed between the cell lineages. One of these, Sox6, was specifically expressed in luminal estrogen receptor negative cells and functional assays confirmed that it maintained mammary epithelial cells in a differentiated luminal cell lineage. Conclusion The mouse mammary epithelium is composed of three main cell types with

  17. Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate.

    Science.gov (United States)

    Kendrick, Howard; Regan, Joseph L; Magnay, Fiona-Ann; Grigoriadis, Anita; Mitsopoulos, Costas; Zvelebil, Marketa; Smalley, Matthew J

    2008-12-08

    Understanding the molecular control of cell lineages and fate determination in complex tissues is key to not only understanding the developmental biology and cellular homeostasis of such tissues but also for our understanding and interpretation of the molecular pathology of diseases such as cancer. The prerequisite for such an understanding is detailed knowledge of the cell types that make up such tissues, including their comprehensive molecular characterisation. In the mammary epithelium, the bulk of the tissue is composed of three cell lineages, namely the basal/myoepithelial, luminal epithelial estrogen receptor positive and luminal epithelial estrogen receptor negative cells. However, a detailed molecular characterisation of the transcriptomic differences between these three populations has not been carried out. A whole transcriptome analysis of basal/myoepithelial cells, luminal estrogen receptor negative cells and luminal estrogen receptor positive cells isolated from the virgin mouse mammary epithelium identified 861, 326 and 488 genes as highly differentially expressed in the three cell types, respectively. Network analysis of the transcriptomic data identified a subpopulation of luminal estrogen receptor negative cells with a novel potential role as non-professional immune cells. Analysis of the data for potential paracrine interacting factors showed that the basal/myoepithelial cells, remarkably, expressed over twice as many ligands and cell surface receptors as the other two populations combined. A number of transcriptional regulators were also identified that were differentially expressed between the cell lineages. One of these, Sox6, was specifically expressed in luminal estrogen receptor negative cells and functional assays confirmed that it maintained mammary epithelial cells in a differentiated luminal cell lineage. The mouse mammary epithelium is composed of three main cell types with distinct gene expression patterns. These suggest the existence

  18. Evolutionary analysis of vision genes identifies potential drivers of visual differences between giraffe and okapi

    Directory of Open Access Journals (Sweden)

    Edson Ishengoma

    2017-04-01

    Full Text Available Background The capacity of visually oriented species to perceive and respond to visual signal is integral to their evolutionary success. Giraffes are closely related to okapi, but the two species have broad range of phenotypic differences including their visual capacities. Vision studies rank giraffe’s visual acuity higher than all other artiodactyls despite sharing similar vision ecological determinants with many of them. The extent to which the giraffe’s unique visual capacity and its difference with okapi is reflected by changes in their vision genes is not understood. Methods The recent availability of giraffe and okapi genomes provided opportunity to identify giraffe and okapi vision genes. Multiple strategies were employed to identify thirty-six candidate mammalian vision genes in giraffe and okapi genomes. Quantification of selection pressure was performed by a combination of branch-site tests of positive selection and clade models of selection divergence through comparing giraffe and okapi vision genes and orthologous sequences from other mammals. Results Signatures of selection were identified in key genes that could potentially underlie giraffe and okapi visual adaptations. Importantly, some genes that contribute to optical transparency of the eye and those that are critical in light signaling pathway were found to show signatures of adaptive evolution or selection divergence. Comparison between giraffe and other ruminants identifies significant selection divergence in CRYAA and OPN1LW. Significant selection divergence was identified in SAG while positive selection was detected in LUM when okapi is compared with ruminants and other mammals. Sequence analysis of OPN1LW showed that at least one of the sites known to affect spectral sensitivity of the red pigment is uniquely divergent between giraffe and other ruminants. Discussion By taking a systemic approach to gene function in vision, the results provide the first molecular clues

  19. Evolutionary analysis of vision genes identifies potential drivers of visual differences between giraffe and okapi.

    Science.gov (United States)

    Ishengoma, Edson; Agaba, Morris; Cavener, Douglas R

    2017-01-01

    The capacity of visually oriented species to perceive and respond to visual signal is integral to their evolutionary success. Giraffes are closely related to okapi, but the two species have broad range of phenotypic differences including their visual capacities. Vision studies rank giraffe's visual acuity higher than all other artiodactyls despite sharing similar vision ecological determinants with many of them. The extent to which the giraffe's unique visual capacity and its difference with okapi is reflected by changes in their vision genes is not understood. The recent availability of giraffe and okapi genomes provided opportunity to identify giraffe and okapi vision genes. Multiple strategies were employed to identify thirty-six candidate mammalian vision genes in giraffe and okapi genomes. Quantification of selection pressure was performed by a combination of branch-site tests of positive selection and clade models of selection divergence through comparing giraffe and okapi vision genes and orthologous sequences from other mammals. Signatures of selection were identified in key genes that could potentially underlie giraffe and okapi visual adaptations. Importantly, some genes that contribute to optical transparency of the eye and those that are critical in light signaling pathway were found to show signatures of adaptive evolution or selection divergence. Comparison between giraffe and other ruminants identifies significant selection divergence in CRYAA and OPN1LW . Significant selection divergence was identified in SAG while positive selection was detected in LUM when okapi is compared with ruminants and other mammals. Sequence analysis of OPN1LW showed that at least one of the sites known to affect spectral sensitivity of the red pigment is uniquely divergent between giraffe and other ruminants. By taking a systemic approach to gene function in vision, the results provide the first molecular clues associated with giraffe and okapi vision adaptations. At

  20. A multiplexed analysis approach identifies new association of inflammatory proteins in patients with overactive bladder.

    Science.gov (United States)

    Ma, Emily; Vetter, Joel; Bliss, Laura; Lai, H Henry; Mysorekar, Indira U; Jain, Sanjay

    2016-07-01

    Overactive bladder (OAB) is a common debilitating bladder condition with unknown etiology and limited diagnostic modalities. Here, we explored a novel high-throughput and unbiased multiplex approach with cellular and molecular components in a well-characterized patient cohort to identify biomarkers that could be reliably used to distinguish OAB from controls or provide insights into underlying etiology. As a secondary analysis, we determined whether this method could discriminate between OAB and other chronic bladder conditions. We analyzed plasma samples from healthy volunteers (n = 19) and patients diagnosed with OAB, interstitial cystitis/bladder pain syndrome (IC/BPS), or urinary tract infections (UTI; n = 51) for proinflammatory, chemokine, cytokine, angiogenesis, and vascular injury factors using Meso Scale Discovery (MSD) analysis and urinary cytological analysis. Wilcoxon rank-sum tests were used to perform univariate and multivariate comparisons between patient groups (controls, OAB, IC/BPS, and UTI). Multivariate logistic regression models were fit for each MSD analyte on 1) OAB patients and controls, 2) OAB and IC/BPS patients, and 3) OAB and UTI patients. Age, race, and sex were included as independent variables in all multivariate analysis. Receiver operating characteristic (ROC) curves were generated to determine the diagnostic potential of a given analyte. Our findings demonstrate that five analytes, i.e., interleukin 4, TNF-α, macrophage inflammatory protein-1β, serum amyloid A, and Tie2 can reliably differentiate OAB relative to controls and can be used to distinguish OAB from the other conditions. Together, our pilot study suggests a molecular imbalance in inflammatory proteins may contribute to OAB pathogenesis. Copyright © 2016 the American Physiological Society.

  1. Quantitative proteomics and integrative network analysis identified novel genes and pathways related to osteoporosis.

    Science.gov (United States)

    Zeng, Yong; Zhang, Lan; Zhu, Wei; Xu, Chao; He, Hao; Zhou, Yu; Liu, Yao-Zhong; Tian, Qing; Zhang, Ji-Gang; Deng, Fei-Yan; Hu, Hong-Gang; Zhang, Li-Shu; Deng, Hong-Wen

    2016-06-16

    Osteoporosis is mainly characterized by low bone mineral density (BMD), and can be attributed to excessive bone resorption by osteoclasts. Migration of circulating monocytes from blood to bone is important for subsequent osteoclast differentiation and bone resorption. Identification of those genes and pathways related to osteoclastogenesis and BMD will contribute to a better understanding of the pathophysiological mechanisms of osteoporosis. In this study, we applied the LC-nano-ESI-MS(E) (Liquid Chromatograph-nano-Electrospray Ionization-Mass Spectrometry) for quantitative proteomic profiling in 33 female Caucasians with discordant BMD levels, with 16 high vs. 17 low BMD subjects. Protein quantitation was accomplished by label-free measurement of total ion currents collected from MS(E) data. Comparison of protein expression in high vs. low BMD subjects showed that ITGA2B (p=0.0063) and GSN (p=0.019) were up-regulated in the high BMD group. Additionally, our protein-RNA integrative analysis showed that RHOA (p=0.00062) differentially expressed between high vs. low BMD groups. Network analysis based on multiple tools revealed two pathways: "regulation of actin cytoskeleton" (p=1.13E-5, FDR=3.34E-4) and "leukocyte transendothelial migration" (p=2.76E-4, FDR=4.71E-3) that are functionally relevant to osteoporosis. Consistently, ITGA2B, GSN and RHOA played crucial roles in these two pathways respectively. All together, our study strongly supported the contribution of the genes ITGA2B, GSN and RHOA and the two pathways to osteoporosis risk. Mass spectrometry based quantitative proteomics study integrated with network analysis identified novel genes and pathways related to osteoporosis. The results were further verified in multiple level studies including protein-RNA integrative analysis and genome wide association studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Automated local bright feature image analysis of nuclear proteindistribution identifies changes in tissue phenotype

    Energy Technology Data Exchange (ETDEWEB)

    Knowles, David; Sudar, Damir; Bator, Carol; Bissell, Mina

    2006-02-01

    The organization of nuclear proteins is linked to cell and tissue phenotypes. When cells arrest proliferation, undergo apoptosis, or differentiate, the distribution of nuclear proteins changes. Conversely, forced alteration of the distribution of nuclear proteins modifies cell phenotype. Immunostaining and fluorescence microscopy have been critical for such findings. However, there is an increasing need for quantitative analysis of nuclear protein distribution to decipher epigenetic relationships between nuclear structure and cell phenotype, and to unravel the mechanisms linking nuclear structure and function. We have developed imaging methods to quantify the distribution of fluorescently-stained nuclear protein NuMA in different mammary phenotypes obtained using three-dimensional cell culture. Automated image segmentation of DAPI-stained nuclei was generated to isolate thousands of nuclei from three-dimensional confocal images. Prominent features of fluorescently-stained NuMA were detected using a novel local bright feature analysis technique, and their normalized spatial density calculated as a function of the distance from the nuclear perimeter to its center. The results revealed marked changes in the distribution of the density of NuMA bright features as non-neoplastic cells underwent phenotypically normal acinar morphogenesis. In contrast, we did not detect any reorganization of NuMA during the formation of tumor nodules by malignant cells. Importantly, the analysis also discriminated proliferating non-neoplastic cells from proliferating malignant cells, suggesting that these imaging methods are capable of identifying alterations linked not only to the proliferation status but also to the malignant character of cells. We believe that this quantitative analysis will have additional applications for classifying normal and pathological tissues.

  3. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles.

    Science.gov (United States)

    Farshidfar, Farshad; Zheng, Siyuan; Gingras, Marie-Claude; Newton, Yulia; Shih, Juliann; Robertson, A Gordon; Hinoue, Toshinori; Hoadley, Katherine A; Gibb, Ewan A; Roszik, Jason; Covington, Kyle R; Wu, Chia-Chin; Shinbrot, Eve; Stransky, Nicolas; Hegde, Apurva; Yang, Ju Dong; Reznik, Ed; Sadeghi, Sara; Pedamallu, Chandra Sekhar; Ojesina, Akinyemi I; Hess, Julian M; Auman, J Todd; Rhie, Suhn K; Bowlby, Reanne; Borad, Mitesh J; Zhu, Andrew X; Stuart, Josh M; Sander, Chris; Akbani, Rehan; Cherniack, Andrew D; Deshpande, Vikram; Mounajjed, Taofic; Foo, Wai Chin; Torbenson, Michael S; Kleiner, David E; Laird, Peter W; Wheeler, David A; McRee, Autumn J; Bathe, Oliver F; Andersen, Jesper B; Bardeesy, Nabeel; Roberts, Lewis R; Kwong, Lawrence N

    2017-03-14

    Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Thermoluminescence analysis can identify irradiated ingredient in soy sauce before and after pasteurization

    Science.gov (United States)

    Lee, Jeong-Eun; Sanyal, Bhaskar; Akram, Kashif; Jo, Yunhee; Baek, Ji-Yeong; Kwon, Joong-Ho

    2017-05-01

    Thermoluminescence (TL) analysis was conducted to identify small quantities (0.5%, 1%, and 1.5%) of γ ray-or electron beam-irradiated garlic powder in a soy sauce after commercial pasteurization. The sauce samples with γ ray- and electron beam-irradiated (0, 1 or 10 kGy) garlic powder showed detectable TL glow curves, characterized by radiation-induced maximum in the temperature range of 180-225 °C. The successful identification of soy sauces with an irradiation history was dependent on both the mixing ratio of the irradiated ingredient and the irradiation dose. Post-irradiation pasteurization (85 °C, 30 min) caused no considerable changes in TL glow shape or intensity. Interlaboratory tests demonstrated that the shape and intensity of the first TL glow curve (TL1) could be a better detection marker than a TL ratio (TL1/TL2).

  5. Using the Contextual Hub Analysis Tool (CHAT) in Cytoscape to Identify Contextually Relevant Network Hubs.

    Science.gov (United States)

    Muetze, Tanja; Lynn, David J

    2017-09-13

    Highly connected nodes in biological networks are called network hubs. Hubs are topologically important to the structure of the network and have been shown to be preferentially associated with a range of phenotypes of interest. The relative importance of a hub node, however, can change depending on the biological context. Here, we provide a step-by-step protocol for using the Contextual Hub Analysis Tool (CHAT), an application within Cytoscape 3, which enables users to easily construct and visualize a network of interactions from a gene or protein list of interest, integrate contextual information, such as gene or protein expression data, and identify hub nodes that are more highly connected to contextual nodes than expected by chance. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

  6. Default-Mode Network Activity Identified by Group Independent Component Analysis

    Science.gov (United States)

    Liu, Conghui; Zhuang, Jie; Peng, Danling; Yu, Guoliang; Yang, Yanhui

    Default-mode network activity refers to some regional increase in blood oxygenation level-dependent (BOLD) signal during baseline than cognitive tasks. Recent functional imaging studies have found co-activation in a distributed network of cortical regions, including ventral anterior cingulate cortex (vACC) and posterior cingulate cortex (PPC) that characterize the default mode of human brain. In this study, general linear model and group independent component analysis (ICA) were utilized to analyze the fMRI data obtained from two language tasks. Both methods yielded similar, but not identical results and detected a resting deactivation network at some midline regions including anterior and posterior cingulate cortex and precuneus. Particularly, the group ICA method segregated functional elements into two separate maps and identified ventral cingulate component and fronto-parietal component. These results suggest that these two components might be linked to different mental function during "resting" baseline.

  7. Identifying time measurement tampering in the traversal time and hop count analysis (TTHCA) wormhole detection algorithm.

    Science.gov (United States)

    Karlsson, Jonny; Dooley, Laurence S; Pulkkis, Göran

    2013-05-17

    Traversal time and hop count analysis (TTHCA) is a recent wormhole detection algorithm for mobile ad hoc networks (MANET) which provides enhanced detection performance against all wormhole attack variants and network types. TTHCA involves each node measuring the processing time of routing packets during the route discovery process and then delivering the measurements to the source node. In a participation mode (PM) wormhole where malicious nodes appear in the routing tables as legitimate nodes, the time measurements can potentially be altered so preventing TTHCA from successfully detecting the wormhole. This paper analyses the prevailing conditions for time tampering attacks to succeed for PM wormholes, before introducing an extension to the TTHCA detection algorithm called ∆T Vector which is designed to identify time tampering, while preserving low false positive rates. Simulation results confirm that the ∆T Vector extension is able to effectively detect time tampering attacks, thereby providing an important security enhancement to the TTHCA algorithm.

  8. Identifying Time Measurement Tampering in the Traversal Time and Hop Count Analysis (TTHCA Wormhole Detection Algorithm

    Directory of Open Access Journals (Sweden)

    Jonny Karlsson

    2013-05-01

    Full Text Available Traversal time and hop count analysis (TTHCA is a recent wormhole detection algorithm for mobile ad hoc networks (MANET which provides enhanced detection performance against all wormhole attack variants and network types. TTHCA involves each node measuring the processing time of routing packets during the route discovery process and then delivering the measurements to the source node. In a participation mode (PM wormhole where malicious nodes appear in the routing tables as legitimate nodes, the time measurements can potentially be altered so preventing TTHCA from successfully detecting the wormhole. This paper analyses the prevailing conditions for time tampering attacks to succeed for PM wormholes, before introducing an extension to the TTHCA detection algorithm called ∆T Vector which is designed to identify time tampering, while preserving low false positive rates. Simulation results confirm that the ∆T Vector extension is able to effectively detect time tampering attacks, thereby providing an important security enhancement to the TTHCA algorithm.

  9. Identifying classes of persons with mild intellectual disability or borderline intellectual functioning: a latent class analysis.

    Science.gov (United States)

    Nouwens, Peter J G; Lucas, Rosanne; Smulders, Nienke B M; Embregts, Petri J C M; van Nieuwenhuizen, Chijs

    2017-07-17

    Persons with mild intellectual disability or borderline intellectual functioning are often studied as a single group with similar characteristics. However, there are indications that differences exist within this population. Therefore, the aim of this study was to identify classes of persons with mild intellectual disability or borderline intellectual functioning and to examine whether these classes are related to individual and/or environmental characteristics. Latent class analysis was performed using file data of 250 eligible participants with a mean age of 26.1 (SD 13.8, range 3-70) years. Five distinct classes of persons with mild intellectual disability or borderline intellectual functioning were found. These classes significantly differed in individual and environmental characteristics. For example, persons with a mild intellectual disability experienced fewer problems than those with borderline intellectual disability. The identification of five classes implies that a differentiated approach is required towards persons with mild intellectual disability or borderline intellectual functioning.

  10. Higher-Order Spectral Analysis to Identify Quadratic Nonlinearities in Fluid-Structure Interaction

    Directory of Open Access Journals (Sweden)

    Imran Akhtar

    2018-01-01

    Full Text Available Hydrodynamic forces on a structure are the manifestation of fluid-structure interaction. Since this interaction is nonlinear, these forces consist of various frequencies: fundamental, harmonics, excitation, sum, and difference of these frequencies. To analyze this phenomenon, we perform numerical simulations of the flow past stationary and oscillating cylinders at low Reynolds numbers. We compute the pressure, integrate it over the surface, and obtain the lift and drag coefficients for the two configurations: stationary and transversely oscillating cylinders. Higher-order spectral analysis is performed to investigate the nonlinear interaction between the forces. We confirmed and investigated the quadratic coupling between the lift and drag coefficients and their phase relationship. We identify additional frequencies and their corresponding energy present in the flow field that appear as the manifestation of quadratic nonlinear interaction.

  11. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

    Directory of Open Access Journals (Sweden)

    Farshad Farshidfar

    2017-03-01

    Full Text Available Cholangiocarcinoma (CCA is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahepatic CCA cases and propose a molecular classification scheme. We identified an IDH mutant-enriched subtype with distinct molecular features including low expression of chromatin modifiers, elevated expression of mitochondrial genes, and increased mitochondrial DNA copy number. Leveraging the multi-platform data, we observed that ARID1A exhibited DNA hypermethylation and decreased expression in the IDH mutant subtype. More broadly, we found that IDH mutations are associated with an expanded histological spectrum of liver tumors with molecular features that stratify with CCA. Our studies reveal insights into the molecular pathogenesis and heterogeneity of cholangiocarcinoma and provide classification information of potential therapeutic significance.

  12. Integrated analysis of the molecular action of Vorinostat identifies epi-sensitised targets for combination therapy.

    Science.gov (United States)

    Hay, Jodie F; Lappin, Katrina; Liberante, Fabio; Kettyle, Laura M; Matchett, Kyle B; Thompson, Alexander; Mills, Ken I

    2017-09-15

    Several histone deacetylase inhibitors including Vorinostat have received FDA approval for the treatment of haematological malignancies. However, data from these trials indicate that Vorinostat has limited efficacy as a monotherapy, prompting the need for rational design of combination therapies. A number of epi-sensitised pathways, including sonic hedgehog (SHH), were identified in AML cells by integration of global patterns of histone H3 lysine 9 (H3K9) acetylation with transcriptomic analysis following Vorinostat-treatment. Direct targeting of the SHH pathway with SANT-1, following Vorinostat induced epi-sensitisation, resulted in synergistic cell death of AML cells. In addition, xenograft studies demonstrated that combination therapy induced a marked reduction in leukemic burden compared to control or single agents. Together, the data supports epi-sensitisation as a potential component of the strategy for the rational development of combination therapies in AML.

  13. Contextual Hub Analysis Tool (CHAT): A Cytoscape app for identifying contextually relevant hubs in biological networks.

    Science.gov (United States)

    Muetze, Tanja; Goenawan, Ivan H; Wiencko, Heather L; Bernal-Llinares, Manuel; Bryan, Kenneth; Lynn, David J

    2016-01-01

    Highly connected nodes (hubs) in biological networks are topologically important to the structure of the network and have also been shown to be preferentially associated with a range of phenotypes of interest. The relative importance of a hub node, however, can change depending on the biological context. Here, we report a Cytoscape app, the Contextual Hub Analysis Tool (CHAT), which enables users to easily construct and visualize a network of interactions from a gene or protein list of interest, integrate contextual information, such as gene expression or mass spectrometry data, and identify hub nodes that are more highly connected to contextual nodes (e.g. genes or proteins that are differentially expressed) than expected by chance. In a case study, we use CHAT to construct a network of genes that are differentially expressed in Dengue fever, a viral infection. CHAT was used to identify and compare contextual and degree-based hubs in this network. The top 20 degree-based hubs were enriched in pathways related to the cell cycle and cancer, which is likely due to the fact that proteins involved in these processes tend to be highly connected in general. In comparison, the top 20 contextual hubs were enriched in pathways commonly observed in a viral infection including pathways related to the immune response to viral infection. This analysis shows that such contextual hubs are considerably more biologically relevant than degree-based hubs and that analyses which rely on the identification of hubs solely based on their connectivity may be biased towards nodes that are highly connected in general rather than in the specific context of interest. CHAT is available for Cytoscape 3.0+ and can be installed via the Cytoscape App Store ( http://apps.cytoscape.org/apps/chat).

  14. Using exploratory factor analysis of FFQ data to identify dietary patterns among Yup'ik people.

    Science.gov (United States)

    Ryman, Tove K; Austin, Melissa A; Hopkins, Scarlett; Philip, Jacques; O'Brien, Diane; Thummel, Kenneth; Boyer, Bert B

    2014-03-01

    An FFQ developed by the Center for Alaska Native Health Research for studies in Yup'ik people includes market foods and subsistence foods such as moose, seal, waterfowl and salmon that may be related to disease risk. Because the FFQ contains >100 food items, we sought to characterize dietary patterns more simply for use in ongoing pharmacogenomics studies. Exploratory factor analysis was used to derive a small number of 'factors' that explain a substantial amount of the variation in the Yup'ik diet. We estimated factor scores and measured associations with demographic characteristics and biomarkers. South-west Alaska, USA. Yup'ik people (n 358) aged ≥18 years. We identified three factors that each accounted for ≥10 % of the common variance: the first characterized by 'processed foods' (e.g. salty snacks, sweetened cereals); the second by 'fruits and vegetables' (e.g. fresh citrus, potato salad); and the third by 'subsistence foods' (seal or walrus soup, non-oily fish). Participants from coastal communities had higher values for the 'subsistence' factor, whereas participants from inland communities had higher values for the 'fruits and vegetables' factor. A biomarker of marine intake, δ 15N, was correlated with the 'subsistence' factor, whereas a biomarker of corn- and sugarcane-based market food intake, δ 13C, was correlated with 'processed foods'. The exploratory factor analysis identified three factors that appeared to reflect dietary patterns among Yup'ik based on associations with participant characteristics and biomarkers. These factors will be useful for chronic disease studies in this population.

  15. Dietary patterns as identified by factor analysis and colorectal cancer among middle-aged Americans.

    Science.gov (United States)

    Flood, Andrew; Rastogi, Tanuja; Wirfält, Elisabet; Mitrou, Panagiota N; Reedy, Jill; Subar, Amy F; Kipnis, Victor; Mouw, Traci; Hollenbeck, Albert R; Leitzmann, Michael; Schatzkin, Arthur

    2008-07-01

    Although diet has long been suspected as an etiological factor for colorectal cancer, studies of single foods and nutrients have provided inconsistent results. We used factor analysis methods to study associations between dietary patterns and colorectal cancer in middle-aged Americans. Diet was assessed among 293,615 men and 198,767 women in the National Institutes of Health-AARP Diet and Health Study. Principal components factor analysis identified 3 primary dietary patterns: a fruit and vegetables, a diet foods, and a red meat and potatoes pattern. State cancer registries identified 2151 incident cases of colorectal cancer in men and 959 in women between 1995 and 2000. Men with high scores on the fruit and vegetable pattern were at decreased risk [relative risk (RR) for quintile (Q) 5 versus Q1: 0.81; 95% CI: 0.70, 0.93; P for trend = 0.004]. Both men and women had a similar risk reduction with high scores on the diet food factor: men (RR: 0.82; 95% CI: 0.72, 0.94; P for trend = 0.001) and women (RR: 0.87; 95% CI: 0.71, 1.07; P for trend = 0.06). High scores on the red meat factor were associated with increased risk: men (RR: 1.17; 95% CI: 1.02, 1.35; P for trend = 0.14) and women (RR: 1.48; 95% CI: 1.20, 1.83; P for trend = 0.0002). These results suggest that dietary patterns characterized by a low frequency of meat and potato consumption and frequent consumption of fruit and vegetables and fat-reduced foods are consistent with a decreased risk of colorectal cancer.

  16. Identifying knowledge activism in worker health and safety representation: A cluster analysis.

    Science.gov (United States)

    Hall, Alan; Oudyk, John; King, Andrew; Naqvi, Syed; Lewchuk, Wayne

    2016-01-01

    Although worker representation in OHS has been widely recognized as contributing to health and safety improvements at work, few studies have examined the role that worker representatives play in this process. Using a large quantitative sample, this paper seeks to confirm findings from an earlier exploratory qualitative study that worker representatives can be differentiated by the knowledge intensive tactics and strategies that they use to achieve changes in their workplace. Just under 900 worker health and safety representatives in Ontario completed surveys which asked them to report on the amount of time they devoted to different types of representation activities (i.e., technical activities such as inspections and report writing vs. political activities such as mobilizing workers to build support), the kinds of conditions or hazards they tried to address through their representation (e.g., housekeeping vs. modifications in ventilation systems), and their reported success in making positive improvements. A cluster analysis was used to determine whether the worker representatives could be distinguished in terms of the relative time devoted to different activities and the clusters were then compared with reference to types of intervention efforts and outcomes. The cluster analysis identified three distinct groupings of representatives with significant differences in reported types of interventions and in their level of reported impact. Two of the clusters were consistent with the findings in the exploratory study, identified as knowledge activism for greater emphasis on knowledge based political activity and technical-legal representation for greater emphasis on formalized technical oriented procedures and legal regulations. Knowledge activists were more likely to take on challenging interventions and they reported more impact across the full range of interventions. This paper provides further support for the concepts of knowledge activism and technical

  17. RNA-seq analysis identifies an intricate regulatory network controlling cluster root development in white lupin.

    Science.gov (United States)

    Secco, David; Shou, Huixia; Whelan, James; Berkowitz, Oliver

    2014-03-25

    Highly adapted plant species are able to alter their root architecture to improve nutrient uptake and thrive in environments with limited nutrient supply. Cluster roots (CRs) are specialised structures of dense lateral roots formed by several plant species for the effective mining of nutrient rich soil patches through a combination of increased surface area and exudation of carboxylates. White lupin is becoming a model-species allowing for the discovery of gene networks involved in CR development. A greater understanding of the underlying molecular mechanisms driving these developmental processes is important for the generation of smarter plants for a world with diminishing resources to improve food security. RNA-seq analyses for three developmental stages of the CR formed under phosphorus-limited conditions and two of non-cluster roots have been performed for white lupin. In total 133,045,174 high-quality paired-end reads were used for a de novo assembly of the root transcriptome and merged with LAGI01 (Lupinus albus gene index) to generate an improved LAGI02 with 65,097 functionally annotated contigs. This was followed by comparative gene expression analysis. We show marked differences in the transcriptional response across the various cluster root stages to adjust to phosphate limitation by increasing uptake capacity and adjusting metabolic pathways. Several transcription factors such as PLT, SCR, PHB, PHV or AUX/IAA with a known role in the control of meristem activity and developmental processes show an increased expression in the tip of the CR. Genes involved in hormonal responses (PIN, LAX, YUC) and cell cycle control (CYCA/B, CDK) are also differentially expressed. In addition, we identify primary transcripts of miRNAs with established function in the root meristem. Our gene expression analysis shows an intricate network of transcription factors and plant hormones controlling CR initiation and formation. In addition, functional differences between the

  18. Identifying model error in metabolic flux analysis - a generalized least squares approach.

    Science.gov (United States)

    Sokolenko, Stanislav; Quattrociocchi, Marco; Aucoin, Marc G

    2016-09-13

    The estimation of intracellular flux through traditional metabolic flux analysis (MFA) using an overdetermined system of equations is a well established practice in metabolic engineering. Despite the continued evolution of the methodology since its introduction, there has been little focus on validation and identification of poor model fit outside of identifying "gross measurement error". The growing complexity of metabolic models, which are increasingly generated from genome-level data, has necessitated robust validation that can directly assess model fit. In this work, MFA calculation is framed as a generalized least squares (GLS) problem, highlighting the applicability of the common t-test for model validation. To differentiate between measurement and model error, we simulate ideal flux profiles directly from the model, perturb them with estimated measurement error, and compare their validation to real data. Application of this strategy to an established Chinese Hamster Ovary (CHO) cell model shows how fluxes validated by traditional means may be largely non-significant due to a lack of model fit. With further simulation, we explore how t-test significance relates to calculation error and show that fluxes found to be non-significant have 2-4 fold larger error (if measurement uncertainty is in the 5-10 % range). The proposed validation method goes beyond traditional detection of "gross measurement error" to identify lack of fit between model and data. Although the focus of this work is on t-test validation and traditional MFA, the presented framework is readily applicable to other regression analysis methods and MFA formulations.

  19. Power analysis as a tool to identify statistically informative indicators for monitoring coral reef disturbances.

    Science.gov (United States)

    Van Wynsberge, Simon; Gilbert, Antoine; Guillemot, Nicolas; Heintz, Tom; Tremblay-Boyer, Laura

    2017-07-01

    Extensive biological field surveys are costly and time consuming. To optimize sampling and ensure regular monitoring on the long term, identifying informative indicators of anthropogenic disturbances is a priority. In this study, we used 1800 candidate indicators by combining metrics measured from coral, fish, and macro-invertebrate assemblages surveyed from 2006 to 2012 in the vicinity of an ongoing mining project in the Voh-Koné-Pouembout lagoon, New Caledonia. We performed a power analysis to identify a subset of indicators which would best discriminate temporal changes due to a simulated chronic anthropogenic impact. Only 4% of tested indicators were likely to detect a 10% annual decrease of values with sufficient power (>0.80). Corals generally exerted higher statistical power than macro-invertebrates and fishes because of lower natural variability and higher occurrence. For the same reasons, higher taxonomic ranks provided higher power than lower taxonomic ranks. Nevertheless, a number of families of common sedentary or sessile macro-invertebrates and fishes also performed well in detecting changes: Echinometridae, Isognomidae, Muricidae, Tridacninae, Arcidae, and Turbinidae for macro-invertebrates and Pomacentridae, Labridae, and Chaetodontidae for fishes. Interestingly, these families did not provide high power in all geomorphological strata, suggesting that the ability of indicators in detecting anthropogenic impacts was closely linked to reef geomorphology. This study provides a first operational step toward identifying statistically relevant indicators of anthropogenic disturbances in New Caledonia's coral reefs, which can be useful in similar tropical reef ecosystems where little information is available regarding the responses of ecological indicators to anthropogenic disturbances.

  20. Analysis of KERA in four families with cornea plana identifies two novel mutations.

    Science.gov (United States)

    Dudakova, Lubica; Vercruyssen, Jang Hee J; Balikova, Irina; Postolache, Lavina; Leroy, Bart P; Skalicka, Pavlina; Liskova, Petra

    2018-02-01

    To identify the molecular genetic cause in four families of various ethnic backgrounds with cornea plana. Detailed ophthalmological examination and direct sequencing of the KERA coding region in five patients of Czech and Turkish origin and their available family members. Compound heterozygosity for a novel missense mutation c.209C>T; p.(Pro70Leu) and a novel splice site mutation c.887-1G>A in KERA were detected in two affected siblings of Czech origin. In silico analysis supported the pathogenicity of both variants. The second proband of Czech origin harboured c.835C>T; p.(Arg279*) in a homozygous state. Homozygous mutations c.740A>G; p.(Asn247Ser) and c.674C>T; p.(Ile225Thr) were identified in the Turkish probands, both born out of consanguineous marriages. Observed ocular phenotypes were typical of cornea plana with the exception of one Czech patient who also had marked thinning and protrusion in the superior part of the left cornea (mean keratometry 47.2 D). No corneal endothelial cell pathology was found by specular microscopy in seven eyes, in three eyes visualization of the posterior corneal surface was unsuccessful. KERA mutation c.740A>G has been identified to date in three different populations, which makes it the most frequently occurring mutation in patients with cornea plana. Marked corneal thinning and ectasia are a very rare finding in this disorder and longitudinal follow-up needs to be performed to determine its potential progressive nature. © 2017 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

  1. The Source and Evolutionary History of a Microbial Contaminant Identified Through Soil Metagenomic Analysis

    Directory of Open Access Journals (Sweden)

    Matthew R. Olm

    2017-02-01

    Full Text Available In this study, strain-resolved metagenomics was used to solve a mystery. A 6.4-Mbp complete closed genome was recovered from a soil metagenome and found to be astonishingly similar to that of Delftia acidovorans SPH-1, which was isolated in Germany a decade ago. It was suspected that this organism was not native to the soil sample because it lacked the diversity that is characteristic of other soil organisms; this suspicion was confirmed when PCR testing failed to detect the bacterium in the original soil samples. D. acidovorans was also identified in 16 previously published metagenomes from multiple environments, but detailed-scale single nucleotide polymorphism analysis grouped these into five distinct clades. All of the strains indicated as contaminants fell into one clade. Fragment length anomalies were identified in paired reads mapping to the contaminant clade genotypes only. This finding was used to establish that the DNA was present in specific size selection reagents used during sequencing. Ultimately, the source of the contaminant was identified as bacterial biofilms growing in tubing. On the basis of direct measurement of the rate of fixation of mutations across the period of time in which contamination was occurring, we estimated the time of separation of the contaminant strain from the genomically sequenced ancestral population within a factor of 2. This research serves as a case study of high-resolution microbial forensics and strain tracking accomplished through metagenomics-based comparative genomics. The specific case reported here is unusual in that the study was conducted in the background of a soil metagenome and the conclusions were confirmed by independent methods.

  2. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

    Science.gov (United States)

    Voight, Benjamin F; Scott, Laura J; Steinthorsdottir, Valgerdur; Morris, Andrew P; Dina, Christian; Welch, Ryan P; Zeggini, Eleftheria; Huth, Cornelia; Aulchenko, Yurii S; Thorleifsson, Gudmar; McCulloch, Laura J; Ferreira, Teresa; Grallert, Harald; Amin, Najaf; Wu, Guanming; Willer, Cristen J; Raychaudhuri, Soumya; McCarroll, Steve A; Langenberg, Claudia; Hofmann, Oliver M; Dupuis, Josée; Qi, Lu; Segrè, Ayellet V; van Hoek, Mandy; Navarro, Pau; Ardlie, Kristin; Balkau, Beverley; Benediktsson, Rafn; Bennett, Amanda J; Blagieva, Roza; Boerwinkle, Eric; Bonnycastle, Lori L; Boström, Kristina Bengtsson; Bravenboer, Bert; Bumpstead, Suzannah; Burtt, Noisël P; Charpentier, Guillaume; Chines, Peter S; Cornelis, Marilyn; Couper, David J; Crawford, Gabe; Doney, Alex S F; Elliott, Katherine S; Elliott, Amanda L; Erdos, Michael R; Fox, Caroline S; Franklin, Christopher S; Ganser, Martha; Gieger, Christian; Grarup, Niels; Green, Todd; Griffin, Simon; Groves, Christopher J; Guiducci, Candace; Hadjadj, Samy; Hassanali, Neelam; Herder, Christian; Isomaa, Bo; Jackson, Anne U; Johnson, Paul R V; Jørgensen, Torben; Kao, Wen H L; Klopp, Norman; Kong, Augustine; Kraft, Peter; Kuusisto, Johanna; Lauritzen, Torsten; Li, Man; Lieverse, Aloysius; Lindgren, Cecilia M; Lyssenko, Valeriya; Marre, Michel; Meitinger, Thomas; Midthjell, Kristian; Morken, Mario A; Narisu, Narisu; Nilsson, Peter; Owen, Katharine R; Payne, Felicity; Perry, John R B; Petersen, Ann-Kristin; Platou, Carl; Proença, Christine; Prokopenko, Inga; Rathmann, Wolfgang; Rayner, N William; Robertson, Neil R; Rocheleau, Ghislain; Roden, Michael; Sampson, Michael J; Saxena, Richa; Shields, Beverley M; Shrader, Peter; Sigurdsson, Gunnar; Sparsø, Thomas; Strassburger, Klaus; Stringham, Heather M; Sun, Qi; Swift, Amy J; Thorand, Barbara; Tichet, Jean; Tuomi, Tiinamaija; van Dam, Rob M; van Haeften, Timon W; van Herpt, Thijs; van Vliet-Ostaptchouk, Jana V; Walters, G Bragi; Weedon, Michael N; Wijmenga, Cisca; Witteman, Jacqueline; Bergman, Richard N; Cauchi, Stephane; Collins, Francis S; Gloyn, Anna L; Gyllensten, Ulf; Hansen, Torben; Hide, Winston A; Hitman, Graham A; Hofman, Albert; Hunter, David J; Hveem, Kristian; Laakso, Markku; Mohlke, Karen L; Morris, Andrew D; Palmer, Colin N A; Pramstaller, Peter P; Rudan, Igor; Sijbrands, Eric; Stein, Lincoln D; Tuomilehto, Jaakko; Uitterlinden, Andre; Walker, Mark; Wareham, Nicholas J; Watanabe, Richard M; Abecasis, Gonçalo R; Boehm, Bernhard O; Campbell, Harry; Daly, Mark J; Hattersley, Andrew T; Hu, Frank B; Meigs, James B; Pankow, James S; Pedersen, Oluf; Wichmann, H-Erich; Barroso, Inês; Florez, Jose C; Frayling, Timothy M; Groop, Leif; Sladek, Rob; Thorsteinsdottir, Unnur; Wilson, James F; Illig, Thomas; Froguel, Philippe; van Duijn, Cornelia M; Stefansson, Kari; Altshuler, David; Boehnke, Michael; McCarthy, Mark I

    2011-01-01

    By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combinedP < 5 × 10−8. These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits. PMID:20581827

  3. Epidemiological analysis of Salmonella clusters identified by whole genome sequencing, England and Wales 2014.

    Science.gov (United States)

    Waldram, Alison; Dolan, Gayle; Ashton, Philip M; Jenkins, Claire; Dallman, Timothy J

    2018-05-01

    The unprecedented level of bacterial strain discrimination provided by whole genome sequencing (WGS) presents new challenges with respect to the utility and interpretation of the data. Whole genome sequences from 1445 isolates of Salmonella belonging to the most commonly identified serotypes in England and Wales isolated between April and August 2014 were analysed. Single linkage single nucleotide polymorphism thresholds at the 10, 5 and 0 level were explored for evidence of epidemiological links between clustered cases. Analysis of the WGS data organised 566 of the 1445 isolates into 32 clusters of five or more. A statistically significant epidemiological link was identified for 17 clusters. The clusters were associated with foreign travel (n = 8), consumption of Chinese takeaways (n = 4), chicken eaten at home (n = 2), and one each of the following; eating out, contact with another case in the home and contact with reptiles. In the same time frame, one cluster was detected using traditional outbreak detection methods. WGS can be used for the highly specific and highly sensitive detection of biologically related isolates when epidemiological links are obscured. Improvements in the collection of detailed, standardised exposure information would enhance cluster investigations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Phylogenetic Analysis of Rubella Viruses Identified in Uganda, 2003–2012

    Science.gov (United States)

    Namuwulya, Prossy; Abernathy, Emily; Bukenya, Henry; Bwogi, Josephine; Tushabe, Phionah; Birungi, Molly; Seguya, Ronald; Kabaliisa, Theopista; Alibu, Vincent P.; Kayondo, Jonathan K.; Rivailler, Pierre; Icenogle, Joseph; Bakamutumaho, Barnabas

    2014-01-01

    Molecular data on rubella viruses are limited in Uganda despite the importance of congenital rubella syndrome (CRS). Routine rubella vaccination, while not administered currently in Uganda, is expected to begin by 2015. The World Health Organization recommends that countries without rubella vaccination programs assess the burden of rubella and CRS before starting a routine vaccination program. Uganda is already involved in integrated case-based surveillance, including laboratory testing to confirm measles and rubella, but molecular epidemiologic aspects of rubella circulation have so far not been documented in Uganda. Twenty throat swab or oral fluid samples collected from 12 districts during routine rash and fever surveillance between 2003 and 2012 were identified as rubella virus RNA positive and PCR products encompassing the region used for genotyping were sequenced. Phylogenetic analysis of the 20 sequences identified 19 genotype 1G viruses and 1 genotype 1E virus. Genotype-specific trees showed that the Uganda viruses belonged to specific clusters for both genotypes 1G and 1E and grouped with similar sequences from neighboring countries. Genotype 1G was predominant in Uganda. More epidemiological and molecular epidemiological data are required to determine if genotype 1E is also endemic in Uganda. The information obtained in this study will assist the immunization program in monitoring changes in circulating genotypes. PMID:24700073

  5. Interstitial Cystitis-Associated Urinary Metabolites Identified by Mass-Spectrometry Based Metabolomics Analysis

    Science.gov (United States)

    Kind, Tobias; Cho, Eunho; Park, Taeeun D.; Deng, Nan; Liu, Zhenqiu; Lee, Tack; Fiehn, Oliver; Kim, Jayoung

    2016-01-01

    This study on interstitial cystitis (IC) aims to identify a unique urine metabolomic profile associated with IC, which can be defined as an unpleasant sensation including pain and discomfort related to the urinary bladder, without infection or other identifiable causes. Although the burden of IC on the American public is immense in both human and financial terms, there is no clear diagnostic test for IC, but rather it is a disease of exclusion. Very little is known about the clinically useful urinary biomarkers of IC, which are desperately needed. Untargeted comprehensive metabolomic profiling was performed using gas-chromatography/mass-spectrometry to compare urine specimens of IC patients or health donors. The study profiled 200 known and 290 unknown metabolites. The majority of the thirty significantly changed metabolites before false discovery rate correction were unknown compounds. Partial least square discriminant analysis clearly separated IC patients from controls. The high number of unknown compounds hinders useful biological interpretation of such predictive models. Given that urine analyses have great potential to be adapted in clinical practice, research has to be focused on the identification of unknown compounds to uncover important clues about underlying disease mechanisms. PMID:27976711

  6. Deep Proteome Analysis Identifies Age-Related Processes in C. elegans.

    Science.gov (United States)

    Narayan, Vikram; Ly, Tony; Pourkarimi, Ehsan; Murillo, Alejandro Brenes; Gartner, Anton; Lamond, Angus I; Kenyon, Cynthia

    2016-08-01

    Effective network analysis of protein data requires high-quality proteomic datasets. Here, we report a near doubling in coverage of the C. elegans adult proteome, identifying >11,000 proteins in total with ∼9,400 proteins reproducibly detected in three biological replicates. Using quantitative mass spectrometry, we identify proteins whose abundances vary with age, revealing a concerted downregulation of proteins involved in specific metabolic pathways and upregulation of cellular stress responses with advancing age. Among these are ∼30 peroxisomal proteins, including the PRX-5/PEX5 import protein. Functional experiments confirm that protein import into the peroxisome is compromised in vivo in old animals. We also studied the behavior of the set of age-variant proteins in chronologically age-matched, long-lived daf-2 insulin/IGF-1-pathway mutants. Unexpectedly, the levels of many of these age-variant proteins did not scale with extended lifespan. This indicates that, despite their youthful appearance and extended lifespans, not all aspects of aging are reset in these long-lived mutants. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  7. Exome sequencing and network analysis identifies shared mechanisms underlying spinocerebellar ataxia.

    Science.gov (United States)

    Nibbeling, Esther A R; Duarri, Anna; Verschuuren-Bemelmans, Corien C; Fokkens, Michiel R; Karjalainen, Juha M; Smeets, Cleo J L M; de Boer-Bergsma, Jelkje J; van der Vries, Gerben; Dooijes, Dennis; Bampi, Giovana B; van Diemen, Cleo; Brunt, Ewout; Ippel, Elly; Kremer, Berry; Vlak, Monique; Adir, Noam; Wijmenga, Cisca; van de Warrenburg, Bart P C; Franke, Lude; Sinke, Richard J; Verbeek, Dineke S

    2017-11-01

    The autosomal dominant cerebellar ataxias, referred to as spinocerebellar ataxias in genetic nomenclature, are a rare group of progressive neurodegenerative disorders characterized by loss of balance and coordination. Despite the identification of numerous disease genes, a substantial number of cases still remain without a genetic diagnosis. Here, we report five novel spinocerebellar ataxia genes, FAT2, PLD3, KIF26B, EP300, and FAT1, identified through a combination of exome sequencing in genetically undiagnosed families and targeted resequencing of exome candidates in a cohort of singletons. We validated almost all genes genetically, assessed damaging effects of the gene variants in cell models and further consolidated a role for several of these genes in the aetiology of spinocerebellar ataxia through network analysis. Our work links spinocerebellar ataxia to alterations in synaptic transmission and transcription regulation, and identifies these as the main shared mechanisms underlying the genetically diverse spinocerebellar ataxia types. © The Author (2017). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Analysis of Pigeon (Columba Ovary Transcriptomes to Identify Genes Involved in Blue Light Regulation.

    Directory of Open Access Journals (Sweden)

    Ying Wang

    Full Text Available Monochromatic light is widely applied to promote poultry reproductive performance, yet little is currently known regarding the mechanism by which light wavelengths affect pigeon reproduction. Recently, high-throughput sequencing technologies have been used to provide genomic information for solving this problem. In this study, we employed Illumina Hiseq 2000 to identify differentially expressed genes in ovary tissue from pigeons under blue and white light conditions and de novo transcriptome assembly to construct a comprehensive sequence database containing information on the mechanisms of follicle development. A total of 157,774 unigenes (mean length: 790 bp were obtained by the Trinity program, and 35.83% of these unigenes were matched to genes in a non-redundant protein database. Gene description, gene ontology, and the clustering of orthologous group terms were performed to annotate the transcriptome assembly. Differentially expressed genes between blue and white light conditions included those related to oocyte maturation, hormone biosynthesis, and circadian rhythm. Furthermore, 17,574 SSRs and 533,887 potential SNPs were identified in this transcriptome assembly. This work is the first transcriptome analysis of the Columba ovary using Illumina technology, and the resulting transcriptome and differentially expressed gene data can facilitate further investigations into the molecular mechanism of the effect of blue light on follicle development and reproduction in pigeons and other bird species.

  9. Supervised multivariate analysis of sequence groups to identify specificity determining residues

    Directory of Open Access Journals (Sweden)

    Higgins Desmond G

    2007-04-01

    Full Text Available Abstract Background Proteins that evolve from a common ancestor can change functionality over time, and it is important to be able identify residues that cause this change. In this paper we show how a supervised multivariate statistical method, Between Group Analysis (BGA, can be used to identify these residues from families of proteins with different substrate specifities using multiple sequence alignments. Results We demonstrate the usefulness of this method on three different test cases. Two of these test cases, the Lactate/Malate dehydrogenase family and Nucleotidyl Cyclases, consist of two functional groups. The other family, Serine Proteases consists of three groups. BGA was used to analyse and visualise these three families using two different encoding schemes for the amino acids. Conclusion This overall combination of methods in this paper is powerful and flexible while being computationally very fast and simple. BGA is especially useful because it can be used to analyse any number of functional classes. In the examples we used in this paper, we have only used 2 or 3 classes for demonstration purposes but any number can be used and visualised.

  10. SPM analysis of parametric (R)-[11C]PK11195 binding images: plasma input versus reference tissue parametric methods

    NARCIS (Netherlands)

    Schuitemaker, Alie; van Berckel, Bart N. M.; Kropholler, Marc A.; Veltman, Dick J.; Scheltens, Philip; Jonker, Cees; Lammertsma, Adriaan A.; Boellaard, Ronald

    2007-01-01

    (R)-[11C]PK11195 has been used for quantifying cerebral microglial activation in vivo. In previous studies, both plasma input and reference tissue methods have been used, usually in combination with a region of interest (ROI) approach. Definition of ROIs, however, can be labourious and prone to

  11. Diversity in Older Adults’ Use of the Internet: Identifying Subgroups Through Latent Class Analysis

    Science.gov (United States)

    van Boekel, Leonieke C; Peek, Sebastiaan TM; Luijkx, Katrien G

    2017-01-01

    Background As for all individuals, the Internet is important in the everyday life of older adults. Research on older adults’ use of the Internet has merely focused on users versus nonusers and consequences of Internet use and nonuse. Older adults are a heterogeneous group, which may implicate that their use of the Internet is diverse as well. Older adults can use the Internet for different activities, and this usage can be of influence on benefits the Internet can have for them. Objective The aim of this paper was to describe the diversity or heterogeneity in the activities for which older adults use the Internet and determine whether diversity is related to social or health-related variables. Methods We used data of a national representative Internet panel in the Netherlands. Panel members aged 65 years and older and who have access to and use the Internet were selected (N=1418). We conducted a latent class analysis based on the Internet activities that panel members reported to spend time on. Second, we described the identified clusters with descriptive statistics and compared the clusters using analysis of variance (ANOVA) and chi-square tests. Results Four clusters were distinguished. Cluster 1 was labeled as the “practical users” (36.88%, n=523). These respondents mainly used the Internet for practical and financial purposes such as searching for information, comparing products, and banking. Respondents in Cluster 2, the “minimizers” (32.23%, n=457), reported lowest frequency on most Internet activities, are older (mean age 73 years), and spent the smallest time on the Internet. Cluster 3 was labeled as the “maximizers” (17.77%, n=252); these respondents used the Internet for various activities, spent most time on the Internet, and were relatively younger (mean age below 70 years). Respondents in Cluster 4, the “social users,” mainly used the Internet for social and leisure-related activities such as gaming and social network sites. The

  12. Diversity in Older Adults' Use of the Internet: Identifying Subgroups Through Latent Class Analysis.

    Science.gov (United States)

    van Boekel, Leonieke C; Peek, Sebastiaan Tm; Luijkx, Katrien G

    2017-05-24

    As for all individuals, the Internet is important in the everyday life of older adults. Research on older adults' use of the Internet has merely focused on users versus nonusers and consequences of Internet use and nonuse. Older adults are a heterogeneous group, which may implicate that their use of the Internet is diverse as well. Older adults can use the Internet for different activities, and this usage can be of influence on benefits the Internet can have for them. The aim of this paper was to describe the diversity or heterogeneity in the activities for which older adults use the Internet and determine whether diversity is related to social or health-related variables. We used data of a national representative Internet panel in the Netherlands. Panel members aged 65 years and older and who have access to and use the Internet were selected (N=1418). We conducted a latent class analysis based on the Internet activities that panel members reported to spend time on. Second, we described the identified clusters with descriptive statistics and compared the clusters using analysis of variance (ANOVA) and chi-square tests. Four clusters were distinguished. Cluster 1 was labeled as the "practical users" (36.88%, n=523). These respondents mainly used the Internet for practical and financial purposes such as searching for information, comparing products, and banking. Respondents in Cluster 2, the "minimizers" (32.23%, n=457), reported lowest frequency on most Internet activities, are older (mean age 73 years), and spent the smallest time on the Internet. Cluster 3 was labeled as the "maximizers" (17.77%, n=252); these respondents used the Internet for various activities, spent most time on the Internet, and were relatively younger (mean age below 70 years). Respondents in Cluster 4, the "social users," mainly used the Internet for social and leisure-related activities such as gaming and social network sites. The identified clusters significantly differed in age (PInternet

  13. Global analysis of p53-regulated transcription identifies its direct targets and unexpected regulatory mechanisms.

    Science.gov (United States)

    Allen, Mary Ann; Andrysik, Zdenek; Dengler, Veronica L; Mellert, Hestia S; Guarnieri, Anna; Freeman, Justin A; Sullivan, Kelly D; Galbraith, Matthew D; Luo, Xin; Kraus, W Lee; Dowell, Robin D; Espinosa, Joaquin M

    2014-05-27

    The p53 transcription factor is a potent suppressor of tumor growth. We report here an analysis of its direct transcriptional program using Global Run-On sequencing (GRO-seq). Shortly after MDM2 inhibition by Nutlin-3, low levels of p53 rapidly activate ∼200 genes, most of them not previously established as direct targets. This immediate response involves all canonical p53 effector pathways, including apoptosis. Comparative global analysis of RNA synthesis vs steady state levels revealed that microarray profiling fails to identify low abundance transcripts directly activated by p53. Interestingly, p53 represses a subset of its activation targets before MDM2 inhibition. GRO-seq uncovered a plethora of gene-specific regulatory features affecting key survival and apoptotic genes within the p53 network. p53 regulates hundreds of enhancer-derived RNAs. Strikingly, direct p53 targets harbor pre-activated enhancers highly transcribed in p53 null cells. Altogether, these results enable the study of many uncharacterized p53 target genes and unexpected regulatory mechanisms.DOI: http://dx.doi.org/10.7554/eLife.02200.001. Copyright © 2014, Allen et al.

  14. Identifying nurse managers' essential communication skills: an analysis of nurses' perceptions in Oman.

    Science.gov (United States)

    Rouse, Ruby A; Al-Maqbali, Majid

    2014-03-01

    The aim of the present study was to analyse nurses' perceptions of the communication qualities that are essential for nurse managers to carry out their jobs effectively. An examination of effective communication may help to identify nurse manager behaviours that promote dignity and respect. A paper-and-pencil survey collected open-ended data from 1526 nursing professionals (RNs) representing 22 hospitals in Oman. Qualitative content analysis was conducted first, followed by a quantitative descriptive analysis. The participants reported frustration with nurse managers who seemed overly focused on mistakes. Many participants felt there was little to no appreciation for tasks that were well done. Nurses also disliked being disciplined openly in front of colleagues or patients. The participants stressed that nurse manager feedback should be shared privately and framed in a positive and constructive tone. Active listening, team collaboration and the avoidance of discrimination/favouritism were also emphasised. A supportive and communicative work environment promotes nurses' dignity and respect. Embarrassing nurses in front of other health care professionals may be counterproductive. Instead, the study results suggested privately discussing concerns in a positive, constructive tone is more likely to foster nurse trust and dignity. © 2014 John Wiley & Sons Ltd.

  15. Identifying differences in the experience of (in)authenticity: a latent class analysis approach.

    Science.gov (United States)

    Lenton, Alison P; Slabu, Letitia; Bruder, Martin; Sedikides, Constantine

    2014-01-01

    Generally, psychologists consider state authenticity - that is, the subjective sense of being one's true self - to be a unitary and unidimensional construct, such that (a) the phenomenological experience of authenticity is thought to be similar no matter its trigger, and (b) inauthenticity is thought to be simply the opposing pole (on the same underlying construct) of authenticity. Using latent class analysis, we put this conceptualization to a test. In order to avoid over-reliance on a Western conceptualization of authenticity, we used a cross-cultural sample (N = 543), comprising participants from Western, South-Asian, East-Asian, and South-East Asian cultures. Participants provided either a narrative in which the described when they felt most like being themselves or one in which they described when they felt least like being themselves. The analysis identified six distinct classes of experiences: two authenticity classes ("everyday" and "extraordinary"), three inauthenticity classes ("self-conscious," "deflated," and "extraordinary"), and a class representing convergence between authenticity and inauthenticity. The classes were phenomenologically distinct, especially with respect to negative affect, private and public self-consciousness, and self-esteem. Furthermore, relatively more interdependent cultures were less likely to report experiences of extraordinary (in)authenticity than relatively more independent cultures. Understanding the many facets of (in)authenticity may enable researchers to connect different findings and explain why the attainment of authenticity can be difficult.

  16. Functional analysis of TPM domain containing Rv2345 of Mycobacterium tuberculosis identifies its phosphatase activity.

    Science.gov (United States)

    Sinha, Avni; Eniyan, Kandasamy; Sinha, Swati; Lynn, Andrew Michael; Bajpai, Urmi

    2015-07-01

    Mycobacterium tuberculosis (Mtb) is the causal agent of tuberculosis, the second largest infectious disease. With the rise of multi-drug resistant strains of M. tuberculosis, serious challenge lies ahead of us in treating the disease. The availability of complete genome sequence of Mtb has improved the scope for identifying new proteins that would not only further our understanding of biology of the organism but could also serve to discover new drug targets. In this study, Rv2345, a hypothetical membrane protein of M. tuberculosis H37Rv, which is reported to be a putative ortholog of ZipA cell division protein has been assigned function through functional annotation using bioinformatics tools followed by experimental validation. Sequence analysis showed Rv2345 to have a TPM domain at its N-terminal region and predicted it to have phosphatase activity. The TPM domain containing region of Rv2345 was cloned and expressed using pET28a vector in Escherichia coli and purified by Nickel affinity chromatography. The purified TPM domain was tested in vitro and our results confirmed it to have phosphatase activity. The enzyme activity was first checked and optimized with pNPP as substrate, followed by using ATP, which was also found to be used as substrate by the purified protein. Hence sequence analysis followed by in vitro studies characterizes TPM domain of Rv2345 to contain phosphatase activity. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Integrative genomic analysis identifies isoleucine and CodY as regulators of Listeria monocytogenes virulence.

    Directory of Open Access Journals (Sweden)

    Lior Lobel

    2012-09-01

    Full Text Available Intracellular bacterial pathogens are metabolically adapted to grow within mammalian cells. While these adaptations are fundamental to the ability to cause disease, we know little about the relationship between the pathogen's metabolism and virulence. Here we used an integrative Metabolic Analysis Tool that combines transcriptome data with genome-scale metabolic models to define the metabolic requirements of Listeria monocytogenes during infection. Twelve metabolic pathways were identified as differentially active during L. monocytogenes growth in macrophage cells. Intracellular replication requires de novo synthesis of histidine, arginine, purine, and branch chain amino acids (BCAAs, as well as catabolism of L-rhamnose and glycerol. The importance of each metabolic pathway during infection was confirmed by generation of gene knockout mutants in the respective pathways. Next, we investigated the association of these metabolic requirements in the regulation of L. monocytogenes virulence. Here we show that limiting BCAA concentrations, primarily isoleucine, results in robust induction of the master virulence activator gene, prfA, and the PrfA-regulated genes. This response was specific and required the nutrient responsive regulator CodY, which is known to bind isoleucine. Further analysis demonstrated that CodY is involved in prfA regulation, playing a role in prfA activation under limiting conditions of BCAAs. This study evidences an additional regulatory mechanism underlying L. monocytogenes virulence, placing CodY at the crossroads of metabolism and virulence.

  18. Genome-Wide Analysis to Identify HLA Factors Potentially Associated With Severe Dengue

    Directory of Open Access Journals (Sweden)

    Sudheer Gupta

    2018-04-01

    Full Text Available The pathogenesis of dengue hemorrhagic fever (DHF, following dengue virus (DENV infection, is a complex and poorly understood phenomenon. In view of the clinical need of identifying patients with higher likelihood of developing this severe outcome, we undertook a comparative genome-wide association analysis of epitope variants from sequences available in the ViPR database that have been reported to be differentially related to dengue fever and DHF. Having enumerated the incriminated epitope variants, we determined the corresponding HLA alleles in the context of which DENV infection could potentially precipitate DHF. Our analysis considered the development of DHF in three different perspectives: (a as a consequence of primary DENV infection, (b following secondary DENV infection with a heterologous serotype, (c as a result of DENV infection following infection with related flaviviruses like Zika virus, Japanese Encephalitis virus, West Nile virus, etc. Subject to experimental validation, these viral and host markers would be valuable in triaging DENV-infected patients for closer supervision owing to the relatively higher risk of poor prognostic outcome and also for the judicious allocation of scarce institutional resources during large outbreaks.

  19. Generic Meal Patterns Identified by Latent Class Analysis: Insights from NANS (National Adult Nutrition Survey

    Directory of Open Access Journals (Sweden)

    Irina Uzhova

    2018-03-01

    Full Text Available Nutritional data reduction methods are widely applied in nutrition epidemiology in order to classify individuals into meaningful groups with similar dietary patterns. To date, none of the existing studies have applied latent class analysis to examine dietary patterns which include meal types consumed throughout a day. We investigated main meal patterns followed on weekend and weekdays, and evaluated their associations with cardio-metabolic biomarkers. The analyses were performed within the NANS (National Adult Nutrition Survey a cross-sectional national food consumption survey of 1500 nationally representative Irish adults. A total number of seven dietary patterns were identified using latent class analysis. The typical meal pattern followed by the majority of the population was characterized by consumption of cereal or toast for breakfast, skipping or consuming a sandwich for light meal, and meat or fish with potatoes, pasta or vegetables for the main meal. Eating patterns differed on weekends, and those participants who consumed meat and eggs for breakfast instead of breakfast cereal and skipped light meal were more likely to have an unhealthier dietary pattern, a higher diastolic blood pressure, and increased serum ferritin. The application of data reduction techniques to simplify the multifaceted nature of dietary data is a useful approach to derive patterns, which might shed further light on the typical dietary patterns followed by populations.

  20. Generic Meal Patterns Identified by Latent Class Analysis: Insights from NANS (National Adult Nutrition Survey).

    Science.gov (United States)

    Uzhova, Irina; Woolhead, Clara; Timon, Claire M; O'Sullivan, Aifric; Brennan, Lorraine; Peñalvo, José L; Gibney, Eileen R

    2018-03-06

    Nutritional data reduction methods are widely applied in nutrition epidemiology in order to classify individuals into meaningful groups with similar dietary patterns. To date, none of the existing studies have applied latent class analysis to examine dietary patterns which include meal types consumed throughout a day. We investigated main meal patterns followed on weekend and weekdays, and evaluated their associations with cardio-metabolic biomarkers. The analyses were performed within the NANS (National Adult Nutrition Survey) a cross-sectional national food consumption survey of 1500 nationally representative Irish adults. A total number of seven dietary patterns were identified using latent class analysis. The typical meal pattern followed by the majority of the population was characterized by consumption of cereal or toast for breakfast, skipping or consuming a sandwich for light meal, and meat or fish with potatoes, pasta or vegetables for the main meal. Eating patterns differed on weekends, and those participants who consumed meat and eggs for breakfast instead of breakfast cereal and skipped light meal were more likely to have an unhealthier dietary pattern, a higher diastolic blood pressure, and increased serum ferritin. The application of data reduction techniques to simplify the multifaceted nature of dietary data is a useful approach to derive patterns, which might shed further light on the typical dietary patterns followed by populations.

  1. The Source and Evolutionary History of a Microbial Contaminant Identified Through Soil Metagenomic Analysis.

    Science.gov (United States)

    Olm, Matthew R; Butterfield, Cristina N; Copeland, Alex; Boles, T Christian; Thomas, Brian C; Banfield, Jillian F

    2017-02-21

    In this study, strain-resolved metagenomics was used to solve a mystery. A 6.4-Mbp complete closed genome was recovered from a soil metagenome and found to be astonishingly similar to that of Delftia acidovorans SPH-1, which was isolated in Germany a decade ago. It was suspected that this organism was not native to the soil sample because it lacked the diversity that is characteristic of other soil organisms; this suspicion was confirmed when PCR testing failed to detect the bacterium in the original soil samples. D. acidovorans was also identified in 16 previously published metagenomes from multiple environments, but detailed-scale single nucleotide polymorphism analysis grouped these into five distinct clades. All of the strains indicated as contaminants fell into one clade. Fragment length anomalies were identified in paired reads mapping to the contaminant clade genotypes only. This finding was used to establish that the DNA was present in specific size selection reagents used during sequencing. Ultimately, the source of the contaminant was identified as bacterial biofilms growing in tubing. On the basis of direct measurement of the rate of fixation of mutations across the period of time in which contamination was occurring, we estimated the time of separation of the contaminant strain from the genomically sequenced ancestral population within a factor of 2. This research serves as a case study of high-resolution microbial forensics and strain tracking accomplished through metagenomics-based comparative genomics. The specific case reported here is unusual in that the study was conducted in the background of a soil metagenome and the conclusions were confirmed by independent methods. IMPORTANCE It is often important to determine the source of a microbial strain. Examples include tracking a bacterium linked to a disease epidemic, contaminating the food supply, or used in bioterrorism. Strain identification and tracking are generally approached by using

  2. Lowly methylated region analysis identifies EBF1 as a potential epigenetic modifier in breast cancer.

    Science.gov (United States)

    Fernandez-Jimenez, Nora; Sklias, Athena; Ecsedi, Szilvia; Cahais, Vincent; Degli-Esposti, Davide; Jay, Antonin; Ancey, Pierre Benoit; Woo, Hae Dong; Hernandez-Vargas, Hector; Herceg, Zdenko

    2017-01-01

    Breast cancer (BC) encompasses heterogeneous pathologies with different subtypes exhibiting distinct molecular changes, including those related to DNA methylation. However, the role of these changes in mediating BC heterogeneity is poorly understood. Lowly methylated regions (LMRs), non-CpG island loci that usually contain transcription factor (TF) binding sites, have been suggested to act as regulatory elements that define cellular identity. In this study, we aimed to identify the key subtype-specific TFs that may lead to LMR generation and shape the BC methylome and transcription program. We initially used whole-genome bisulfite sequencing (WGBS) data available at The Cancer Genome Atlas (TCGA) portal to identify subtype-specific LMRs. Differentially methylated regions (DMRs) within the BC PAM50 subtype-specific LMRs were selected by comparing tumors and normal tissues in a larger TCGA cohort assessed by HumanMethylation450 BeadChip (450K) arrays and TF enrichment analyses were performed. To assess the impact of LMRs on gene expression, TCGA RNA sequencing data were downloaded and Pearson correlations between methylation levels of loci presenting subtype-specific TF motifs and expression of the nearest genes were calculated. WGBS methylome data revealed a large number of LMRs for each of the BC subtypes. Analysis of these LMRs in the 450K datasets available for a larger sample set identified 7,765, 5,657, and 19 differentially methylated positions (DMPs) between normal adjacent tissues and tumor tissues from basal, luminal, and HER2-enriched subtypes, respectively. Unsupervised clustering showed that the discriminatory power of the top DMPs was remarkably strong for basal BC. Interestingly, in this particular subtype, we found 4,409 differentially hypomethylated positions grouped into 1,185 DMRs with a strong enrichment for the early B-cell factor 1 (EBF1) motifs. The methylation levels of the DMRs containing EBF1 motifs showed a strong negative correlation with

  3. Identifying patterns in treatment response profiles in acute bipolar mania: a cluster analysis approach

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    Houston John P

    2008-07-01

    Full Text Available Abstract Background Patients with acute mania respond differentially to treatment and, in many cases, fail to obtain or sustain symptom remission. The objective of this exploratory analysis was to characterize response in bipolar disorder by identifying groups of patients with similar manic symptom response profiles. Methods Patients (n = 222 were selected from a randomized, double-blind study of treatment with olanzapine or divalproex in bipolar I disorder, manic or mixed episode, with or without psychotic features. Hierarchical clustering based on Ward's distance was used to identify groups of patients based on Young-Mania Rating Scale (YMRS total scores at each of 5 assessments over 7 weeks. Logistic regression was used to identify baseline predictors for clusters of interest. Results Four distinct clusters of patients were identified: Cluster 1 (n = 64: patients did not maintain a response (YMRS total scores ≤ 12; Cluster 2 (n = 92: patients responded rapidly (within less than a week and response was maintained; Cluster 3 (n = 36: patients responded rapidly but relapsed soon afterwards (YMRS ≥ 15; Cluster 4 (n = 30: patients responded slowly (≥ 2 weeks and response was maintained. Predictive models using baseline variables found YMRS Item 10 (Appearance, and psychosis to be significant predictors for Clusters 1 and 4 vs. Clusters 2 and 3, but none of the baseline characteristics allowed discriminating between Clusters 1 vs. 4. Experiencing a mixed episode at baseline predicted membership in Clusters 2 and 3 vs. Clusters 1 and 4. Treatment with divalproex, larger number of previous manic episodes, lack of disruptive-aggressive behavior, and more prominent depressive symptoms at baseline were predictors for Cluster 3 vs. 2. Conclusion Distinct treatment response profiles can be predicted by clinical features at baseline. The presence of these features as potential risk factors for relapse in patients who have responded to treatment

  4. RNA Transcriptional Biosignature Analysis for Identifying Febrile Infants With Serious Bacterial Infections in the Emergency Department

    Science.gov (United States)

    Mahajan, Prashant; Kuppermann, Nathan; Suarez, Nicolas; Mejias, Asuncion; Casper, Charlie; Dean, J. Michael; Ramilo, Octavio

    2015-01-01

    Objectives To develop the infrastructure and demonstrate the feasibility of conducting microarray-based RNA transcriptional profile analyses for the diagnosis of serious bacterial infections in febrile infants 60 days and younger in a multicenter pediatric emergency research network. Methods We designed a prospective multicenter cohort study with the aim of enrolling more than 4000 febrile infants 60 days and younger. To ensure success of conducting complex genomic studies in emergency department (ED) settings, we established an infrastructure within the Pediatric Emergency Care Applied Research Network, including 21 sites, to evaluate RNA transcriptional profiles in young febrile infants. We developed a comprehensive manual of operations and trained site investigators to obtain and process blood samples for RNA extraction and genomic analyses. We created standard operating procedures for blood sample collection, processing, storage, shipping, and analyses. We planned to prospectively identify, enroll, and collect 1 mL blood samples for genomic analyses from eligible patients to identify logistical issues with study procedures. Finally, we planned to batch blood samples and determined RNA quantity and quality at the central microarray laboratory and organized data analysis with the Pediatric Emergency Care Applied Research Network data coordinating center. Below we report on establishment of the infrastructure and the feasibility success in the first year based on the enrollment of a limited number of patients. Results We successfully established the infrastructure at 21 EDs. Over the first 5 months we enrolled 79% (74 of 94) of eligible febrile infants. We were able to obtain and ship 1 mL of blood from 74% (55 of 74) of enrolled participants, with at least 1 sample per participating ED. The 55 samples were shipped and evaluated at the microarray laboratory, and 95% (52 of 55) of blood samples were of adequate quality and contained sufficient RNA for expression

  5. Gene expression analysis to identify molecular correlates of pre- and post-conditioning derived neuroprotection.

    Science.gov (United States)

    Prasad, Shiv S; Russell, Marsha; Nowakowska, Margeryta; Williams, Andrew; Yauk, Carole

    2012-06-01

    Mild ischaemic exposures before or after severe injurious ischaemia that elicit neuroprotective responses are referred to as preconditioning and post-conditioning. The corresponding molecular mechanisms of neuroprotection are not completely understood. Identification of the genes and associated pathways of corresponding neuroprotection would provide insight into neuronal survival, potential therapeutic approaches and assessments of therapies for stroke. The objectives of this study were to use global gene expression approach to infer the molecular mechanisms in pre- and post-conditioning-derived neuroprotection in cortical neurons following oxygen and glucose deprivation (OGD) in vitro and then to apply these findings to predict corresponding functional pathways. To this end, microarray analysis was applied to rat cortical neurons with or without the pre- and post-conditioning treatments at 3-h post-reperfusion, and differentially expressed transcripts were subjected to statistical, hierarchical clustering and pathway analyses. The expression patterns of 3,431 genes altered under all conditions of ischaemia (with and without pre- or post-conditioning). We identified 1,595 genes that were commonly regulated within both the pre- and post-conditioning treatments. Cluster analysis revealed that transcription profiles clustered tightly within controls, non-conditioned OGD and neuroprotected groups. Two clusters defining neuroprotective conditions associated with up- and downregulated genes were evident. The five most upregulated genes within the neuroprotective clusters were Tagln, Nes, Ptrf, Vim and Adamts9, and the five most downregulated genes were Slc7a3, Bex1, Brunol4, Nrxn3 and Cpne4. Pathway analysis revealed that the intracellular and second messenger signalling pathways in addition to cell death were predominantly associated with downregulated pre- and post-conditioning associated genes, suggesting that modulation of cell death and signal transduction pathways

  6. Identify the Effective Wells in Determination of Groundwater Depth in Urmia Plain Using Principle Component Analysis

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    Sahar Babaei Hessar

    2017-06-01

    Full Text Available Introduction: Groundwater is the most important resource of providing sanitary water for potable and household consumption. So continuous monitoring of groundwater level will play an important role in water resource management. But because of the large amount of information, evaluation of water table is a costly and time consuming process. Therefore, in many studies, the data and information aren’t suitable and useful and so, must be neglected. The PCA technique is an optimized mathematical method that reserve data with the highest share in affirming variance with recognizing less important data and limits the original variables into to a few components. In this technique, variation factors called principle components are identified with considering data structures. Thus, variables those have the highest correlation coefficient with principal components are extracted as a result of identifying the components that create the greatest variance. Materials and Methods: The study region has an area of approximately 962 Km2 and area located between 37º 21´ N to 37º 49´ N and 44º 57´ E to 45º 16´ E in West Azerbaijan province of Iran. This area placed along the mountainous north-west of the country, which ends with the plane Urmia Lake and has vast groundwater resources. However, recently the water table has been reduced considerably because of the exceeded exploitation as a result of urbanization and increased agricultural and horticultural land uses. In the present study, the annual water table datasets in 51wells monitored by Ministry of Energy during statistical periods of 2002-2011 were used to data analysis. In order to identify the effective wells in determination of groundwater level, the PCA technique was used. In this research to compute the relative importance of each well, 10 wells were identified with the nearest neighbor for each one. The number of wells (p as a general rule must be less or equal to the maximum number of

  7. The Multimorbidity Cluster Analysis Tool: Identifying Combinations and Permutations of Multiple Chronic Diseases Using a Record-Level Computational Analysis

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    Kathryn Nicholson

    2017-12-01

    Full Text Available Introduction: Multimorbidity, or the co-occurrence of multiple chronic health conditions within an individual, is an increasingly dominant presence and burden in modern health care systems.  To fully capture its complexity, further research is needed to uncover the patterns and consequences of these co-occurring health states.  As such, the Multimorbidity Cluster Analysis Tool and the accompanying Multimorbidity Cluster Analysis Toolkit have been created to allow researchers to identify distinct clusters that exist within a sample of participants or patients living with multimorbidity.  Development: The Tool and Toolkit were developed at Western University in London, Ontario, Canada.  This open-access computational program (JAVA code and executable file was developed and tested to support an analysis of thousands of individual records and up to 100 disease diagnoses or categories.  Application: The computational program can be adapted to the methodological elements of a research project, including type of data, type of chronic disease reporting, measurement of multimorbidity, sample size and research setting.  The computational program will identify all existing, and mutually exclusive, combinations and permutations within the dataset.  An application of this computational program is provided as an example, in which more than 75,000 individual records and 20 chronic disease categories resulted in the detection of 10,411 unique combinations and 24,647 unique permutations among female and male patients.  Discussion: The Tool and Toolkit are now available for use by researchers interested in exploring the complexities of multimorbidity.  Its careful use, and the comparison between results, will be valuable additions to the nuanced understanding of multimorbidity.

  8. Statistics that learn: can logistic discriminant analysis improve diagnosis in brain SPECT?

    International Nuclear Information System (INIS)

    Behin-Ain, S.; Barnden, L.; Kwiatek, R.; Del Fante, P.; Casse, R.; Burnet, R.; Chew, G.; Kitchener, M.; Boundy, K.; Unger, S.

    2002-01-01

    Full text: Logistic discriminant analysis (LDA) is a statistical technique capable of discriminating individuals within a diseased group against normals. It also enables classification of various diseases within a group of patients. This technique provides a quantitative, automated and non-subjective clinical diagnostic tool. Based on a population known to have the disease and a normal control group, an algorithm was developed and trained to identify regions in the human brain responsible for the disease in question. The algorithm outputs a statistical map representing diseased or normal probability on a voxel or cluster basis from which an index is generated for each subject. The algorithm also generates a set of coefficients which is used to generate an index for the purpose of classification of new subjects. The results are comparable and complement those of Statistical Parametric Mapping (SPM) which employs a more common linear discriminant technique. The results are presented for brain SPECT studies of two diseases: chronic fatigue syndrome (CFS) and fibromyalgia (FM). A 100% specificity and 94% sensitivity is achieved for the CFS study (similar to SPM results) and for the FM study 82% specificity and 94% sensitivity is achieved with corresponding SPM results showing 90% specificity and 82% sensitivity. The results encourages application of LDA for discrimination of new single subjects as well as of diseased and normal groups. Copyright (2002) The Australian and New Zealand Society of Nuclear Medicine Inc

  9. Identify Foot of Continental Slope by singular spectrum and fractal singularity analysis

    Science.gov (United States)

    Li, Q.; Dehler, S.

    2012-04-01

    Identifying the Foot of Continental Slope (FOCS) plays a critical role in the determination of exclusive economic zone (EEZ) for coastal nations. The FOCS is defined by the Law of the Sea as the point of maximum change of the slope and it is mathematically equivalent to the point which has the maximum curvature value in its vicinity. However, curvature is the second derivative and the calculation of second derivative is a high pass and noise-prone filtering procedure. Therefore, identification of FOCS with curvature analysis methods is often uncertain and erroneous because observed bathymetry profiles or interpolated raster maps commonly include high frequency noises and artifacts, observation errors, and local sharp changes. Effective low-pass filtering methods and robust FOCS indicator algorithms are highly desirable. In this approach, nonlinear singular spectral filtering and singularity FOCS-indicator methods and software tools are developed to address this requirement. The normally used Fourier domain filtering methods decompose signals into Fourier space, composed of a fixed base that depends only on the acquisition interval of the signal; the signal is required to be stationary or at least weak stationary. In contrast to that requirement, the developed singular spectral filtering method constructs orthogonal basis functions dynamically according to different signals, and it does not require the signal to be stationary or weak stationary. Furthermore, singular spectrum analysis (SSA) can assist in designing suitable filters to carefully remove high-frequency local or noise components while reserving useful global and local components according to energy distribution. Geoscientific signals, including morphological ocean bathymetry data, often demonstrate fractal or multifractal properties. With proper definition of scales in the vicinity of a certain point and related measures, it is found that 1-dimensional bathymetry profiles and 2-dimensional raster maps

  10. Carbon and chlorine isotope analysis to identify abiotic degradation pathways of 1,1,1-trichloroethane.

    Science.gov (United States)

    Palau, Jordi; Shouakar-Stash, Orfan; Hunkeler, Daniel

    2014-12-16

    This study investigates dual C-Cl isotope fractionation during 1,1,1-TCA transformation by heat-activated persulfate (PS), hydrolysis/dehydrohalogenation (HY/DH) and Fe(0). Compound-specific chlorine isotope analysis of 1,1,1-TCA was performed for the first time, and transformation-associated isotope fractionation ε bulk C and ε bulk Cl values were -4.0 ± 0.2‰ and no chlorine isotope fractionation with PS, -1.6 ± 0.2‰ and -4.7 ± 0.1‰ for HY/DH, -7.8 ± 0.4‰ and -5.2 ± 0.2‰ with Fe(0). Distinctly different dual isotope slopes (Δδ13C/Δδ37Cl): ∞ with PS, 0.33 ± 0.04 for HY/DH and 1.5 ± 0.1 with Fe(0) highlight the potential of this approach to identify abiotic degradation pathways of 1,1,1-TCA in the field. The trend observed with PS agreed with a C-H bond oxidation mechanism in the first reaction step. For HY/DH and Fe(0) pathways, different slopes were obtained although both pathways involve cleavage of a C-Cl bond in their initial reaction step. In contrast to the expected larger primary carbon isotope effects relative to chlorine for C-Cl bond cleavage, ε bulk C isotope effects. Therefore, different magnitude of secondary chlorine isotope effects could at least be partly responsible for the distinct slopes between HY/DH and Fe(0) pathways. Following this dual isotope approach, abiotic transformation processes can unambiguously be identified and quantified.

  11. Identifying sources of emerging organic contaminants in a mixed use watershed using principal components analysis.

    Science.gov (United States)

    Karpuzcu, M Ekrem; Fairbairn, David; Arnold, William A; Barber, Brian L; Kaufenberg, Elizabeth; Koskinen, William C; Novak, Paige J; Rice, Pamela J; Swackhamer, Deborah L

    2014-01-01

    Principal components analysis (PCA) was used to identify sources of emerging organic contaminants in the Zumbro River watershed in Southeastern Minnesota. Two main principal components (PCs) were identified, which together explained more than 50% of the variance in the data. Principal Component 1 (PC1) was attributed to urban wastewater-derived sources, including municipal wastewater and residential septic tank effluents, while Principal Component 2 (PC2) was attributed to agricultural sources. The variances of the concentrations of cotinine, DEET and the prescription drugs carbamazepine, erythromycin and sulfamethoxazole were best explained by PC1, while the variances of the concentrations of the agricultural pesticides atrazine, metolachlor and acetochlor were best explained by PC2. Mixed use compounds carbaryl, iprodione and daidzein did not specifically group with either PC1 or PC2. Furthermore, despite the fact that caffeine and acetaminophen have been historically associated with human use, they could not be attributed to a single dominant land use category (e.g., urban/residential or agricultural). Contributions from septic systems did not clarify the source for these two compounds, suggesting that additional sources, such as runoff from biosolid-amended soils, may exist. Based on these results, PCA may be a useful way to broadly categorize the sources of new and previously uncharacterized emerging contaminants or may help to clarify transport pathways in a given area. Acetaminophen and caffeine were not ideal markers for urban/residential contamination sources in the study area and may need to be reconsidered as such in other areas as well.

  12. In-silico analysis of Pasteurella multocida to identify common epitopes between fowl, goat and buffalo.

    Science.gov (United States)

    Ghaffar, Ammarah; Tariq, Aamira

    2016-04-10

    Pasteurella multocida represents a highly diverse group of bacteria infecting various hosts like the fowl, goat and buffalo leading to huge economic loss to the poultry and cattle industry. Previous reports indicated that the outer membrane proteins contribute significantly to the pathogenesis of Pasteurella multocida. The comparative in-silico genome wide analysis of four pathogenic Pasteurella multocida strains (Anand1-poultry, Anand1-goat, PMTB and VTCCBAA264) with their respective hosts was performed. A pipeline was developed to identify the list of non-homologous proteins of Pasteurella multocida strains and their hosts. The list was further analyzed for the identification of the essential outer membrane proteins responsible for the pathogenicity. Outer membrane proteins were further selected from these antigenic proteins on the basis of their pathogenic potential. A common B-cell epitope (TDYRNRDRS, ARRSVTSKEN, and KINDQWRW) determined via sequential and structural approach from the lipopolysaccharide (LPS) assembly outer membrane complex protein was predicted from fowl, goat and buffalo. Furthermore, we identified T-cell epitopes based on the lipopolysaccharide (LPS) assembly outer membrane complex protein via docking studies which were either similar to the B-cell epitopes or were occurring in the same patch except for MHC class II M fowl. We propose that this difference in epitope sequence is due to different interacting MHC class II protein predicted from the fowl. Hence, in the current study we found that a unique epitope based on the common antigenic lipopolysaccharide (LPS) outer membrane complex protein present in fowl, goat and buffalo can be a suitable target for vaccine development against the two economic devastating diseases; fowl cholera (FC) and hemorrhagic septicemia (HS). Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Large scale association analysis identifies three susceptibility loci for coronary artery disease.

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    Stephanie Saade

    Full Text Available Genome wide association studies (GWAS and their replications that have associated DNA variants with myocardial infarction (MI and/or coronary artery disease (CAD are predominantly based on populations of European or Eastern Asian descent. Replication of the most significantly associated polymorphisms in multiple populations with distinctive genetic backgrounds and lifestyles is crucial to the understanding of the pathophysiology of a multifactorial disease like CAD. We have used our Lebanese cohort to perform a replication study of nine previously identified CAD/MI susceptibility loci (LTA, CDKN2A-CDKN2B, CELSR2-PSRC1-SORT1, CXCL12, MTHFD1L, WDR12, PCSK9, SH2B3, and SLC22A3, and 88 genes in related phenotypes. The study was conducted on 2,002 patients with detailed demographic, clinical characteristics, and cardiac catheterization results. One marker, rs6922269, in MTHFD1L was significantly protective against MI (OR=0.68, p=0.0035, while the variant rs4977574 in CDKN2A-CDKN2B was significantly associated with MI (OR=1.33, p=0.0086. Associations were detected after adjustment for family history of CAD, gender, hypertension, hyperlipidemia, diabetes, and smoking. The parallel study of 88 previously published genes in related phenotypes encompassed 20,225 markers, three quarters of which with imputed genotypes The study was based on our genome-wide genotype data set, with imputation across the whole genome to HapMap II release 22 using HapMap CEU population as a reference. Analysis was conducted on both the genotyped and imputed variants in the 88 regions covering selected genes. This approach replicated HNRNPA3P1-CXCL12 association with CAD and identified new significant associations of CDKAL1, ST6GAL1, and PTPRD with CAD. Our study provides evidence for the importance of the multifactorial aspect of CAD/MI and describes genes predisposing to their etiology.

  14. Transcriptional profile analysis of RPGRORF15 frameshift mutation identifies novel genes associated with retinal degeneration.

    Science.gov (United States)

    Genini, Sem; Zangerl, Barbara; Slavik, Julianna; Acland, Gregory M; Beltran, William A; Aguirre, Gustavo D

    2010-11-01

    To identify genes and molecular mechanisms associated with photoreceptor degeneration in a canine model of XLRP caused by an RPGR exon ORF15 microdeletion. Methods. Expression profiles of mutant and normal retinas were compared by using canine retinal custom cDNA microarrays. qRT-PCR, Western blot analysis, and immunohistochemistry (IHC) were applied to selected genes, to confirm and expand the microarray results. At 7 and 16 weeks, respectively, 56 and 18 transcripts were downregulated in the mutant retinas, but none were differentially expressed (DE) at both ages, suggesting the involvement of temporally distinct pathways. Downregulated genes included the known retina-relevant genes PAX6, CHML, and RDH11 at 7 weeks and CRX and SAG at 16 weeks. Genes directly or indirectly active in apoptotic processes were altered at 7 weeks (CAMK2G, NTRK2, PRKCB, RALA, RBBP6, RNF41, SMYD3, SPP1, and TUBB2C) and 16 weeks (SLC25A5 and NKAP). Furthermore, the DE genes at 7 weeks (ELOVL6, GLOD4, NDUFS4, and REEP1) and 16 weeks (SLC25A5 and TARS2) are related to mitochondrial functions. qRT-PCR of 18 genes confirmed the microarray results and showed DE of additional genes not on the array. Only GFAP was DE at 3 weeks of age. Western blot and IHC analyses also confirmed the high reliability of the transcriptomic data. Several DE genes were identified in mutant retinas. At 7 weeks, a combination of nonclassic anti- and proapoptosis genes appear to be involved in photoreceptor degeneration, whereas at both 7 and 16 weeks, the expression of mitochondria-related genes indicates that they may play a relevant role in the disease process.

  15. Novel snail1 target proteins in human colon cancer identified by proteomic analysis.

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    María Jesús Larriba

    2010-04-01

    Full Text Available The transcription factor Snail1 induces epithelial-to-mesenchymal transition (EMT, a process responsible for the acquisition of invasiveness during tumorigenesis. Several transcriptomic studies have reported Snail1-regulated genes in different cell types, many of them involved in cell adhesion. However, only a few studies have used proteomics as a tool for the characterization of proteins mediating EMT.We identified by proteomic analysis using 2D-DIGE electrophoresis combined with MALDI-TOF-TOF and ESI-linear ion trap mass spectrometry a number of proteins with variable functions whose expression is modulated by Snail1 in SW480-ADH human colon cancer cells. Validation was performed by Western blot and immunofluorescence analyses. Snail1 repressed several members of the 14-3-3 family of phosphoserine/phosphothreonine binding proteins and also the expression of the Proliferation-associated protein 2G4 (PA2G4 that was mainly localized at the nuclear Cajal bodies. In contrast, the expression of two proteins involved in RNA processing, the Cleavage and polyadenylation specificity factor subunit 6 (CPSF6 and the Splicing factor proline/glutamine-rich (SFPQ, was higher in Snail1-expressing cells than in controls. The regulation of 14-3-3epsilon, 14-3-3tau, 14-3-3zeta and PA2G4 by Snail1 was reproduced in HT29 colon cancer cells. In addition, we found an inverse correlation between 14-3-3sigma and Snail1 expression in human colorectal tumors.We have identified a set of novel Snail1 target proteins in colon cancer that expand the cellular processes affected by Snail1 and thus its relevance for cell function and phenotype.

  16. Identifying gender-preferred communication styles within online cancer communities: a retrospective, longitudinal analysis.

    Science.gov (United States)

    Durant, Kathleen T; McCray, Alexa T; Safran, Charles

    2012-01-01

    The goal of this research is to determine if different gender-preferred social styles can be observed within the user interactions at an online cancer community. To achieve this goal, we identify and measure variables that pertain to each gender-specific social style. We perform social network and statistical analysis on the communication flow of 8,388 members at six different cancer forums over eight years. Kruskal-Wallis tests were conducted to measure the difference between the number of intimate (and highly intimate) dyads, relationship length, and number of communications. We determine that two patients are more likely to form an intimate bond on a gender-specific cancer forum (ovarian P = communicates with more members than a female patient (Ovarian forum P = 0.0406, Breast forum P = 0.0013). A relationship between two patients is longer on the gender-specific cancer forums than a connection between two members not identified as patients (ovarian forum P = 0.00406, breast forum P = 0.00013, prostate forum P = .0.0003). The high level of interconnectedness among the prostate patients supports the hypothesis that men prefer to socialize in large, interconnected, less-intimate groups. A female patient is more likely to form a highly intimate connection with another female patient; this finding is consistent with the hypothesis that woman prefer fewer, more intimate connections. The relationships of same-gender cancer patients last longer than other relationships; this finding demonstrates homophily within these online communities. Our findings regarding online communication preferences are in agreement with research findings from person-to-person communication preference studies. These findings should be considered when designing online communities as well as designing and evaluating psychosocial and educational interventions for cancer patients.

  17. Genome-wide DNA methylation profile analysis identifies differentially methylated loci associated with ankylosis spondylitis.

    Science.gov (United States)

    Hao, Jiangcan; Liu, Yang; Xu, Jiawen; Wang, Wenyu; Wen, Yan; He, Awen; Fan, Qianrui; Guo, Xiong; Zhang, Feng

    2017-07-25

    Ankylosing spondylitis (AS) is a chronic rheumatic and autoimmune disease. Little is known about the potential role of DNA methylation in the pathogenesis of AS. This study was undertaken to explore the potential role of DNA methylation in the genetic mechanism of AS. In this study, we compared the genome-wide DNA methylation profiles of peripheral blood mononuclear cells (PBMCs) between five AS patients and five healthy subjects, using the Illumina Infinium HumanMethylation450 BeadChip. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was performed to validate the relevance of the identified differentially methylated genes for AS, using another independent sample of five AS patients and five healthy subjects. Compared with healthy controls, we detected 1915 differentially methylated CpG sites mapped to 1214 genes. The HLA-DQB1 gene achieved the most significant signal (cg14323910, adjusted P = 1.84 × 10 -6 , β difference = 0.5634) for AS. Additionally, the CpG site cg04777551 of HLA-DQB1 presented a suggestive association with AS (adjusted P = 1.46 × 10 -3 , β difference = 0.3594). qRT-PCR observed that the mRNA expression level of HLA-DQB1 in AS PBMCs was significantly lower than that in healthy control PBMCs (ratio = 0.48 ± 0.10, P pathway enrichment analysis of differentially methylated genes identified four GO terms and 10 pathways for AS, functionally related to antigen dynamics and function. Our results demonstrated the altered DNA methylation profile of AS and implicated HLA-DQB1 in the development of AS.

  18. Genome wide transcriptome analysis of dendritic cells identifies genes with altered expression in psoriasis.

    Science.gov (United States)

    Filkor, Kata; Hegedűs, Zoltán; Szász, András; Tubak, Vilmos; Kemény, Lajos; Kondorosi, Éva; Nagy, István

    2013-01-01

    Activation of dendritic cells by different pathogens induces the secretion of proinflammatory mediators resulting in local inflammation. Importantly, innate immunity must be properly controlled, as its continuous activation leads to the development of chronic inflammatory diseases such as psoriasis. Lipopolysaccharide (LPS) or peptidoglycan (PGN) induced tolerance, a phenomenon of transient unresponsiveness of cells to repeated or prolonged stimulation, proved valuable model for the study of chronic inflammation. Thus, the aim of this study was the identification of the transcriptional diversity of primary human immature dendritic cells (iDCs) upon PGN induced tolerance. Using SAGE-Seq approach, a tag-based transcriptome sequencing method, we investigated gene expression changes of primary human iDCs upon stimulation or restimulation with Staphylococcus aureus derived PGN, a widely used TLR2 ligand. Based on the expression pattern of the altered genes, we identified non-tolerizeable and tolerizeable genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (Kegg) analysis showed marked enrichment of immune-, cell cycle- and apoptosis related genes. In parallel to the marked induction of proinflammatory mediators, negative feedback regulators of innate immunity, such as TNFAIP3, TNFAIP8, Tyro3 and Mer are markedly downregulated in tolerant cells. We also demonstrate, that the expression pattern of TNFAIP3 and TNFAIP8 is altered in both lesional, and non-lesional skin of psoriatic patients. Finally, we show that pretreatment of immature dendritic cells with anti-TNF-α inhibits the expression of IL-6 and CCL1 in tolerant iDCs and partially releases the suppression of TNFAIP8. Our findings suggest that after PGN stimulation/restimulation the host cell utilizes different mechanisms in order to maintain critical balance between inflammation and tolerance. Importantly, the transcriptome sequencing of stimulated/restimulated iDCs identified numerous genes with

  19. Network analysis of translocated Takahe populations to identify disease surveillance targets.

    Science.gov (United States)

    Grange, Zoë L; VAN Andel, Mary; French, Nigel P; Gartrell, Brett D

    2014-04-01

    Social network analysis is being increasingly used in epidemiology and disease modeling in humans, domestic animals, and wildlife. We investigated this tool in describing a translocation network (area that allows movement of animals between geographically isolated locations) used for the conservation of an endangered flightless rail, the Takahe (Porphyrio hochstetteri). We collated records of Takahe translocations within New Zealand and used social network principles to describe the connectivity of the translocation network. That is, networks were constructed and analyzed using adjacency matrices with values based on the tie weights between nodes. Five annual network matrices were created using the Takahe data set, each incremental year included records of previous years. Weights of movements between connected locations were assigned by the number of Takahe moved. We calculated the number of nodes (i(total)) and the number of ties (t(total)) between the nodes. To quantify the small-world character of the networks, we compared the real networks to random graphs of the equivalent size, weighting, and node strength. Descriptive analysis of cumulative annual Takahe movement networks involved determination of node-level characteristics, including centrality descriptors of relevance to disease modeling such as weighted measures of in degree (k(i)(in)), out degree (k(i)(out)), and betweenness (B(i)). Key players were assigned according to the highest node measure of k(i)(in), k(i)(out), and B(i) per network. Networks increased in size throughout the time frame considered. The network had some degree small-world characteristics. Nodes with the highest cumulative tie weights connecting them were the captive breeding center, the Murchison Mountains and 2 offshore islands. The key player fluctuated between the captive breeding center and the Murchison Mountains. The cumulative networks identified the captive breeding center every year as the hub of the network until the final

  20. Bioinformatics analysis identifies several intrinsically disordered human E3 ubiquitin-protein ligases

    Directory of Open Access Journals (Sweden)

    Wouter Boomsma

    2016-02-01

    Full Text Available The ubiquitin-proteasome system targets misfolded proteins for degradation. Since the accumulation of such proteins is potentially harmful for the cell, their prompt removal is important. E3 ubiquitin-protein ligases mediate substrate ubiquitination by bringing together the substrate with an E2 ubiquitin-conjugating enzyme, which transfers ubiquitin to the substrate. For misfolded proteins, substrate recognition is generally delegated to molecular chaperones that subsequently interact with specific E3 ligases. An important exception is San1, a yeast E3 ligase. San1 harbors extensive regions of intrinsic disorder, which provide both conformational flexibility and sites for direct recognition of misfolded targets of vastly different conformations. So far, no mammalian ortholog of San1 is known, nor is it clear whether other E3 ligases utilize disordered regions for substrate recognition. Here, we conduct a bioinformatics analysis to examine >600 human and S. cerevisiae E3 ligases to identify enzymes that are similar to San1 in terms of function and/or mechanism of substrate recognition. An initial sequence-based database search was found to detect candidates primarily based on the homology of their ordered regions, and did not capture the unique disorder patterns that encode the functional mechanism of San1. However, by searching specifically for key features of the San1 sequence, such as long regions of intrinsic disorder embedded with short stretches predicted to be suitable for substrate interaction, we identified several E3 ligases with these characteristics. Our initial analysis revealed that another remarkable trait of San1 is shared with several candidate E3 ligases: long stretches of complete lysine suppression, which in San1 limits auto-ubiquitination. We encode these characteristic features into a San1 similarity-score, and present a set of proteins that are plausible candidates as San1 counterparts in humans. In conclusion, our work

  1. Meta-analysis of grain yield QTL identified during agricultural drought in grasses showed consensus.

    Science.gov (United States)

    Swamy, B P Mallikarjuna; Vikram, Prashant; Dixit, Shalabh; Ahmed, H U; Kumar, Arvind

    2011-06-16

    In the last few years, efforts have been made to identify large effect QTL for grain yield under drought in rice. However, identification of most precise and consistent QTL across the environments and genetics backgrounds is essential for their successful use in Marker-assisted Selection. In this study, an attempt was made to locate consistent QTL regions associated with yield increase under drought by applying a genome-wide QTL meta-analysis approach. The integration of 15 maps resulted in a consensus map with 531 markers and a total map length of 1821 cM. Fifty-three yield QTL reported in 15 studies were projected on a consensus map and meta-analysis was performed. Fourteen meta-QTL were obtained on seven chromosomes. MQTL1.2, MQTL1.3, MQTL1.4, and MQTL12.1 were around 700 kb and corresponded to a reasonably small genetic distance of 1.8 to 5 cM and they are suitable for use in marker-assisted selection (MAS). The meta-QTL for grain yield under drought coincided with at least one of the meta-QTL identified for root and leaf morphology traits under drought in earlier reports. Validation of major-effect QTL on a panel of random drought-tolerant lines revealed the presence of at least one major QTL in each line. DTY12.1 was present in 85% of the lines, followed by DTY4.1 in 79% and DTY1.1 in 64% of the lines. Comparative genomics of meta-QTL with other cereals revealed that the homologous regions of MQTL1.4 and MQTL3.2 had QTL for grain yield under drought in maize, wheat, and barley respectively. The genes in the meta-QTL regions were analyzed by a comparative genomics approach and candidate genes were deduced for grain yield under drought. Three groups of genes such as stress-inducible genes, growth and development-related genes, and sugar transport-related genes were found in clusters in most of the meta-QTL. Meta-QTL with small genetic and physical intervals could be useful in Marker-assisted selection individually and in combinations. Validation and comparative

  2. Comparative Genomic Analysis Identifies a Campylobacter Clade Deficient in Selenium Metabolism.

    Science.gov (United States)

    Miller, William G; Yee, Emma; Lopes, Bruno S; Chapman, Mary H; Huynh, Steven; Bono, James L; Parker, Craig T; Strachan, Norval J C; Forbes, Ken J

    2017-07-01

    The nonthermotolerant Campylobacter species C. fetus, C. hyointestinalis, C. iguaniorum, and C. lanienae form a distinct phylogenetic cluster within the genus. These species are primarily isolated from foraging (swine) or grazing (e.g., cattle, sheep) animals and cause sporadic and infrequent human illness. Previous typing studies identified three putative novel C. lanienae-related taxa, based on either MLST or atpA sequence data. To further characterize these putative novel taxa and the C. fetus group as a whole, 76 genomes were sequenced, either to completion or to draft level. These genomes represent 26 C. lanienae strains and 50 strains of the three novel taxa. C. fetus, C. hyointestinalis and C. iguaniorum genomes were previously sequenced to completion; therefore, a comparative genomic analysis across the entire C. fetus group was conducted (including average nucleotide identity analysis) that supports the initial identification of these three novel Campylobacter species. Furthermore, C. lanienae and the three putative novel species form a discrete clade within the C. fetus group, which we have termed the C. lanienae clade. This clade is distinguished from other members of the C. fetus group by a reduced genome size and distinct CRISPR/Cas systems. Moreover, there are two signature characteristics of the C. lanienae clade. C. lanienae clade genomes carry four to ten unlinked and similar, but nonidentical, flagellin genes. Additionally, all 76 C. lanienae clade genomes sequenced demonstrate a complete absence of genes related to selenium metabolism, including genes encoding the selenocysteine insertion machinery, selenoproteins, and the selenocysteinyl tRNA. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution 2017. This work is written by US Government employees and is in the public domain in the US.

  3. RNA-seq analysis of Paris polyphylla var. yunnanensis roots identified candidate genes for saponin synthesis

    Directory of Open Access Journals (Sweden)

    Tao Liu

    2016-06-01

    Full Text Available Paris polyphylla Smith var. yunnanensis (Franch. Hand.-Mazz. is a rhizomatous, herbaceous, perennial plant that has been used for more than a thousand years in traditional Chinese medicine. It is facing extinction due to overharvesting. Steroids are the major therapeutic components in Paris roots, the commercial value of which increases with age. To date, no genomic data on the species have been available. In this study, transcriptome analysis of an 8-year-old root and a 4-year-old root provided insight into the metabolic pathways that generate the steroids. Using Illumina sequencing technology, we generated a high-quality sequence and demonstrated de novo assembly and annotation of genes in the absence of prior genome information. Approximately 87,577 unique sequences, with an average length of 614 bases, were obtained from the root cells. Using bioinformatics methods, we annotated approximately 65.51% of the unique sequences by conducting a similarity search with known genes in the National Center for Biotechnology Information's non-redundant database. The unique transcripts were functionally classified using the Gene Ontology hierarchy and the Kyoto Encyclopedia of Genes and Genomes database. Of 3082 genes that were identified as significantly differentially expressed between roots of different ages, 1518 (49.25% were upregulated and 1564 (50.75% were downregulated in the older root. Metabolic pathway analysis predicted that 25 unigenes were responsible for the biosynthesis of the saponins steroids. These data represent a valuable resource for future genomic studies on this endangered species and will be valuable for efforts to genetically engineer P. polyphylla and facilitate saponin-rich plant development.

  4. Comprehensive Analysis of Gene Expression Profiles of Sepsis-Induced Multiorgan Failure Identified Its Valuable Biomarkers.

    Science.gov (United States)

    Wang, Yumei; Yin, Xiaoling; Yang, Fang

    2018-02-01

    Sepsis is an inflammatory-related disease, and severe sepsis would induce multiorgan dysfunction, which is the most common cause of death of patients in noncoronary intensive care units. Progression of novel therapeutic strategies has proven to be of little impact on the mortality of severe sepsis, and unfortunately, its mechanisms still remain poorly understood. In this study, we analyzed gene expression profiles of severe sepsis with failure of lung, kidney, and liver for the identification of potential biomarkers. We first downloaded the gene expression profiles from the Gene Expression Omnibus and performed preprocessing of raw microarray data sets and identification of differential expression genes (DEGs) through the R programming software; then, significantly enriched functions of DEGs in lung, kidney, and liver failure sepsis samples were obtained from the Database for Annotation, Visualization, and Integrated Discovery; finally, protein-protein interaction network was constructed for DEGs based on the STRING database, and network modules were also obtained through the MCODE cluster method. As a result, lung failure sepsis has the highest number of DEGs of 859, whereas the number of DEGs in kidney and liver failure sepsis samples is 178 and 175, respectively. In addition, 17 overlaps were obtained among the three lists of DEGs. Biological processes related to immune and inflammatory response were found to be significantly enriched in DEGs. Network and module analysis identified four gene clusters in which all or most of genes were upregulated. The expression changes of Icam1 and Socs3 were further validated through quantitative PCR analysis. This study should shed light on the development of sepsis and provide potential therapeutic targets for sepsis-induced multiorgan failure.

  5. Transcriptome Analysis Identifies the Dysregulation of Ultraviolet Target Genes in Human Skin Cancers.

    Directory of Open Access Journals (Sweden)

    Yao Shen

    Full Text Available Exposure to ultraviolet radiation (UVR is a major risk factor for both melanoma and non-melanoma skin cancers. In addition to its mutagenic effect, UVR can also induce substantial transcriptional instability in skin cells affecting thousands of genes, including many cancer genes, suggesting that transcriptional instability may be another important etiological factor in skin photocarcinogenesis. In this study, we performed detailed transcriptomic profiling studies to characterize the kinetic changes in global gene expression in human keratinocytes exposed to different UVR conditions. We identified a subset of UV-responsive genes as UV signature genes (UVSGs based on 1 conserved UV-responsiveness of this subset of genes among different keratinocyte lines; and 2 UV-induced persistent changes in their mRNA levels long after exposure. Interestingly, 11 of the UVSGs were shown to be critical to skin cancer cell proliferation and survival. Through computational Gene Set Enrichment Analysis, we demonstrated that a significant portion of the UVSGs were dysregulated in human skin squamous cell carcinomas, but not in other human malignancies. This highlights the potential and specificity of the UVSGs in clinical diagnosis of UV damage and stratification of skin cancer risk.

  6. Antimicrobial susceptibility among clinical Nocardia species identified by multilocus sequence analysis.

    Science.gov (United States)

    McTaggart, Lisa R; Doucet, Jennifer; Witkowska, Maria; Richardson, Susan E

    2015-01-01

    Antimicrobial susceptibility patterns of 112 clinical isolates, 28 type strains, and 9 reference strains of Nocardia were determined using the Sensititre Rapmyco microdilution panel (Thermo Fisher, Inc.). Isolates were identified by highly discriminatory multilocus sequence analysis and were chosen to represent the diversity of species recovered from clinical specimens in Ontario, Canada. Susceptibility to the most commonly used drug, trimethoprim-sulfamethoxazole, was observed in 97% of isolates. Linezolid and amikacin were also highly effective; 100% and 99% of all isolates demonstrated a susceptible phenotype. For the remaining antimicrobials, resistance was species specific with isolates of Nocardia otitidiscaviarum, N. brasiliensis, N. abscessus complex, N. nova complex, N. transvalensis complex, N. farcinica, and N. cyriacigeorgica displaying the traditional characteristic drug pattern types. In addition, the antimicrobial susceptibility profiles of a variety of rarely encountered species isolated from clinical specimens are reported for the first time and were categorized into four additional drug pattern types. Finally, MICs for the control strains N. nova ATCC BAA-2227, N. asteroides ATCC 19247(T), and N. farcinica ATCC 23826 were robustly determined to demonstrate method reproducibility and suitability of the commercial Sensititre Rapmyco panel for antimicrobial susceptibility testing of Nocardia spp. isolated from clinical specimens. The reported values will facilitate quality control and standardization among laboratories. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. Coexpression analysis identifies nuclear reprogramming barriers of somatic cell nuclear transfer embryos.

    Science.gov (United States)

    Zuo, Yongchun; Su, Guanghua; Cheng, Lei; Liu, Kun; Feng, Yu; Wei, Zhuying; Bai, Chunling; Cao, Guifang; Li, Guangpeng

    2017-09-12

    The success of cloned animal "Dolly Sheep" demonstrated the somatic cell nuclear transfer (SCNT) technique holds huge potentials for mammalian asexual reproduction. However, the extremely poor development of SCNT embryos indicates their molecular mechanism remain largely unexplored. Deciphering the spatiotemporal patterns of gene expression in SCNT embryos is a crucial step toward understanding the mechanisms associated with nuclear reprogramming. In this study, a valuable transcriptome recourse of SCNT embryos was firstly established, which derived from different inter-/intra donor cells. The gene co-expression analysis identified 26 cell-specific modules, and a series of regulatory pathways related to reprogramming barriers were further enriched. Compared to the intra-SCNT embryos, the inter-SCNT embryos underwent only complete partially reprogramming. As master genome trigger genes, the transcripts related to TFIID subunit, RNA polymerase and mediators were incomplete activated in inter-SCNT embryos. The inter-SCNT embryos only wasted the stored maternal mRNA of master regulators, but failed to activate their self-sustained pathway of RNA polymerases. The KDM family of epigenetic regulator also seriously delayed in inter-SCNT embryo reprogramming process. Our study provided new insight into understanding of the mechanisms of nuclear reprogramming.

  8. RUSSIAN PATENT LANDSCAPE, CREATED BY THE RESIDENTS OF THE COUNTRY: ANALYSIS OF THE IDENTIFIED ISSUES

    Directory of Open Access Journals (Sweden)

    N. G. Kurakova

    2016-01-01

    Full Text Available It is suggested to reach the goal for channeling limited funds into the most productive research groups inRussiaby identifying so –called leading organisations among the scientific centres. As one of the criteria for selecting organisations with potential for creating the technological breakthrough on global markets will be an indicator of their patent activity. There are presented results of patent analysis, allowing to form a rating of owners of most extensive portfolios of Russian patents, as well as thematic fields, whereRussiademonstrated high levels of innovative activity in the period from 2010 to 2015. It is demonstrated that the structure of patent owners inRussiadefers in princiapl from the one established in industrially developed countries. InRussia, the accumulative share of patents, obtained by individual applicants and universities, amounted to 77,2% for the period under review, weares in developed countries this share hasn’t exceeded 10–15%. The article suggests using modern Russian scientific-technological and industrial politics to solve systematic issues, causing low scientific research intensity of domestic industrial sector, which enjoys less than 13% of patents inRussia, which is six times less than analogue indicators, in industrially developed countries. 

  9. A new method to identify the foot of continental slope based on an integrated profile analysis

    Science.gov (United States)

    Wu, Ziyin; Li, Jiabiao; Li, Shoujun; Shang, Jihong; Jin, Xiaobin

    2017-06-01

    A new method is proposed to identify automatically the foot of the continental slope (FOS) based on the integrated analysis of topographic profiles. Based on the extremum points of the second derivative and the Douglas-Peucker algorithm, it simplifies the topographic profiles, then calculates the second derivative of the original profiles and the D-P profiles. Seven steps are proposed to simplify the original profiles. Meanwhile, multiple identification methods are proposed to determine the FOS points, including gradient, water depth and second derivative values of data points, as well as the concave and convex, continuity and segmentation of the topographic profiles. This method can comprehensively and intelligently analyze the topographic profiles and their derived slopes, second derivatives and D-P profiles, based on which, it is capable to analyze the essential properties of every single data point in the profile. Furthermore, it is proposed to remove the concave points of the curve and in addition, to implement six FOS judgment criteria.

  10. Untargeted metabolomic analysis in naturally occurring canine diabetes mellitus identifies similarities to human Type 1 Diabetes.

    Science.gov (United States)

    O'Kell, Allison L; Garrett, Timothy J; Wasserfall, Clive; Atkinson, Mark A

    2017-08-25

    While predominant as a disease entity, knowledge voids exist regarding the pathogenesis of canine diabetes. To test the hypothesis that diabetic dogs have similar metabolomic perturbations to humans with type 1 diabetes (T1D), we analyzed serum metabolomic profiles of breed- and body weight-matched, diabetic (n = 6) and healthy (n = 6) dogs by liquid chromatography-mass spectrometry (LC-MS) profiling. We report distinct clustering of diabetic and control groups based on heat map analysis of known and unknown metabolites. Random forest classification identified 5/6 dogs per group correctly with overall out of bag error rate = 16.7%. Diabetic dogs demonstrated significant upregulation of glycolysis/gluconeogenesis intermediates (e.g., glucose/fructose, C 6 H 12 O 6 , keto-hexose, deoxy-hexose, (P diabetic versus healthy dogs (P diabetic animals (P diabetic versus healthy dogs shared similarities with those reported in human T1D (e.g., alterations in glycolysis/gluconeogensis metabolites, bile acids, and elevated branched chain AA). Further studies are warranted to evaluate the utility of canine diabetes to provide novel mechanistic insights to the human disorder.

  11. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

    Science.gov (United States)

    Felix, Janine F.; Bradfield, Jonathan P.; Monnereau, Claire; van der Valk, Ralf J.P.; Stergiakouli, Evie; Chesi, Alessandra; Gaillard, Romy; Feenstra, Bjarke; Thiering, Elisabeth; Kreiner-Møller, Eskil; Mahajan, Anubha; Pitkänen, Niina; Joro, Raimo; Cavadino, Alana; Huikari, Ville; Franks, Steve; Groen-Blokhuis, Maria M.; Cousminer, Diana L.; Marsh, Julie A.; Lehtimäki, Terho; Curtin, John A.; Vioque, Jesus; Ahluwalia, Tarunveer S.; Myhre, Ronny; Price, Thomas S.; Vilor-Tejedor, Natalia; Yengo, Loïc; Grarup, Niels; Ntalla, Ioanna; Ang, Wei; Atalay, Mustafa; Bisgaard, Hans; Blakemore, Alexandra I.; Bonnefond, Amelie; Carstensen, Lisbeth; Eriksson, Johan; Flexeder, Claudia; Franke, Lude; Geller, Frank; Geserick, Mandy; Hartikainen, Anna-Liisa; Haworth, Claire M.A.; Hirschhorn, Joel N.; Hofman, Albert; Holm, Jens-Christian; Horikoshi, Momoko; Hottenga, Jouke Jan; Huang, Jinyan; Kadarmideen, Haja N.; Kähönen, Mika; Kiess, Wieland; Lakka, Hanna-Maaria; Lakka, Timo A.; Lewin, Alexandra M.; Liang, Liming; Lyytikäinen, Leo-Pekka; Ma, Baoshan; Magnus, Per; McCormack, Shana E.; McMahon, George; Mentch, Frank D.; Middeldorp, Christel M.; Murray, Clare S.; Pahkala, Katja; Pers, Tune H.; Pfäffle, Roland; Postma, Dirkje S.; Power, Christine; Simpson, Angela; Sengpiel, Verena; Tiesler, Carla M. T.; Torrent, Maties; Uitterlinden, André G.; van Meurs, Joyce B.; Vinding, Rebecca; Waage, Johannes; Wardle, Jane; Zeggini, Eleftheria; Zemel, Babette S.; Dedoussis, George V.; Pedersen, Oluf; Froguel, Philippe; Sunyer, Jordi; Plomin, Robert; Jacobsson, Bo; Hansen, Torben; Gonzalez, Juan R.; Custovic, Adnan; Raitakari, Olli T.; Pennell, Craig E.; Widén, Elisabeth; Boomsma, Dorret I.; Koppelman, Gerard H.; Sebert, Sylvain; Järvelin, Marjo-Riitta; Hyppönen, Elina; McCarthy, Mark I.; Lindi, Virpi; Harri, Niinikoski; Körner, Antje; Bønnelykke, Klaus; Heinrich, Joachim; Melbye, Mads; Rivadeneira, Fernando; Hakonarson, Hakon; Ring, Susan M.; Smith, George Davey; Sørensen, Thorkild I.A.; Timpson, Nicholas J.; Grant, Struan F.A.; Jaddoe, Vincent W.V.

    2016-01-01

    A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10−10) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index. PMID:26604143

  12. Proteomic analysis of polyribosomes identifies splicing factors as potential regulators of translation during mitosis.

    Science.gov (United States)

    Aviner, Ranen; Hofmann, Sarah; Elman, Tamar; Shenoy, Anjana; Geiger, Tamar; Elkon, Ran; Ehrlich, Marcelo; Elroy-Stein, Orna

    2017-06-02

    Precise regulation of mRNA translation is critical for proper cell division, but little is known about the factors that mediate it. To identify mRNA-binding proteins that regulate translation during mitosis, we analyzed the composition of polysomes from interphase and mitotic cells using unbiased quantitative mass-spectrometry (LC-MS/MS). We found that mitotic polysomes are enriched with a subset of proteins involved in RNA processing, including alternative splicing and RNA export. To demonstrate that these may indeed be regulators of translation, we focused on heterogeneous nuclear ribonucleoprotein C (hnRNP C) as a test case and confirmed that it is recruited to elongating ribosomes during mitosis. Then, using a combination of pulsed SILAC, metabolic labeling and ribosome profiling, we showed that knockdown of hnRNP C affects both global and transcript-specific translation rates and found that hnRNP C is specifically important for translation of mRNAs that encode ribosomal proteins and translation factors. Taken together, our results demonstrate how proteomic analysis of polysomes can provide insight into translation regulation under various cellular conditions of interest and suggest that hnRNP C facilitates production of translation machinery components during mitosis to provide daughter cells with the ability to efficiently synthesize proteins as they enter G1 phase. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  13. De Novo Transcriptome Analysis of Allium cepa L. (Onion) Bulb to Identify Allergens and Epitopes.

    Science.gov (United States)

    Rajkumar, Hemalatha; Ramagoni, Ramesh Kumar; Anchoju, Vijayendra Chary; Vankudavath, Raju Naik; Syed, Arshi Uz Zaman

    2015-01-01

    Allium cepa (onion) is a diploid plant with one of the largest nuclear genomes among all diploids. Onion is an example of an under-researched crop which has a complex heterozygous genome. There are no allergenic proteins and genomic data available for onions. This study was conducted to establish a transcriptome catalogue of onion bulb that will enable us to study onion related genes involved in medicinal use and allergies. Transcriptome dataset generated from onion bulb using the Illumina HiSeq 2000 technology showed a total of 99,074,309 high quality raw reads (~20 Gb). Based on sequence homology onion genes were categorized into 49 different functional groups. Most of the genes however, were classified under 'unknown' in all three gene ontology categories. Of the categorized genes, 61.2% showed metabolic functions followed by cellular components such as binding, cellular processes; catalytic activity and cell part. With BLASTx top hit analysis, a total of 2,511 homologous allergenic sequences were found, which had 37-100% similarity with 46 different types of allergens existing in the database. From the 46 contigs or allergens, 521 B-cell linear epitopes were identified using BepiPred linear epitope prediction tool. This is the first comprehensive insight into the transcriptome of onion bulb tissue using the NGS technology, which can be used to map IgE epitopes and prediction of structures and functions of various proteins.

  14. Identifying ideal brow vector position: empirical analysis of three brow archetypes.

    Science.gov (United States)

    Hamamoto, Ashley A; Liu, Tiffany W; Wong, Brian J

    2013-02-01

    Surgical browlifts counteract the effects of aging, correct ptosis, and optimize forehead aesthetics. While surgeons have control over brow shape, the metrics defining ideal brow shape are subjective. This study aims to empirically determine whether three expert brow design strategies are aesthetically equivalent by using expert focus group analysis and relating these findings to brow surgery. Comprehensive literature search identified three dominant brow design methods (Westmore, Lamas and Anastasia) that are heavily cited, referenced or internationally recognized in either medical literature or by the lay media. Using their respective guidelines, brow shape was modified for 10 synthetic female faces, yielding 30 images. A focus group of 50 professional makeup artists ranked the three images for each of the 10 faces to generate ordinal attractiveness scores. The contemporary methods employed by Anastasia and Lamas produce a brow arch more lateral than Westmore's classic method. Although the more laterally located brow arch is considered the current trend in facial aesthetics, this style was not empirically supported. No single method was consistently rated most or least attractive by the focus group, and no significant difference in attractiveness score for the different methods was observed (p = 0.2454). Although each method of brow placement has been promoted as the "best" approach, no single brow design method achieved statistical significance in optimizing attractiveness. Each can be used effectively as a guide in designing eyebrow shape during browlift procedures, making it possible to use the three methods interchangeably. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  15. Competing endogenous RNA network analysis identifies critical genes among the different breast cancer subtypes.

    Science.gov (United States)

    Chen, Juan; Xu, Juan; Li, Yongsheng; Zhang, Jinwen; Chen, Hong; Lu, Jianping; Wang, Zishan; Zhao, Xueying; Xu, Kang; Li, Yixue; Li, Xia; Zhang, Yan

    2017-02-07

    Although competing endogenous RNAs (ceRNAs) have been implicated in many solid tumors, their roles in breast cancer subtypes are not well understood. We therefore generated a ceRNA network for each subtype based on the significance of both, positive co-expression and the shared miRNAs, in the corresponding subtype miRNA dys-regulatory network, which was constructed based on negative regulations between differentially expressed miRNAs and targets. All four subtype ceRNA networks exhibited scale-free architecture and showed that the common ceRNAs were at the core of the networks. Furthermore, the common ceRNA hubs had greater connectivity than the subtype-specific hubs. Functional analysis of the common subtype ceRNA hubs highlighted factors involved in proliferation, MAPK signaling pathways and tube morphogenesis. Subtype-specific ceRNA hubs highlighted unique subtype-specific pathways, like the estrogen response and inflammatory pathways in the luminal subtypes or the factors involved in the coagulation process that participates in the basal-like subtype. Ultimately, we identified 29 critical subtype-specific ceRNA hubs that characterized the different breast cancer subtypes. Our study thus provides new insight into the common and specific subtype ceRNA interactions that define the different categories of breast cancer and enhances our understanding of the pathology underlying the different breast cancer subtypes, which can have prognostic and therapeutic implications in the future.

  16. Sensitivity analysis of the STICS-MACRO model to identify cropping practices reducing pesticides losses.

    Science.gov (United States)

    Lammoglia, Sabine-Karen; Makowski, David; Moeys, Julien; Justes, Eric; Barriuso, Enrique; Mamy, Laure

    2017-02-15

    STICS-MACRO is a process-based model simulating the fate of pesticides in the soil-plant system as a function of agricultural practices and pedoclimatic conditions. The objective of this work was to evaluate the influence of crop management practices on water and pesticide flows in contrasted environmental conditions. We used the Morris screening sensitivity analysis method to identify the most influential cropping practices. Crop residues management and tillage practices were shown to have strong effects on water percolation and pesticide leaching. In particular, the amount of organic residues added to soil was found to be the most influential input. The presence of a mulch could increase soil water content so water percolation and pesticide leaching. Conventional tillage was also found to decrease pesticide leaching, compared to no-till, which is consistent with many field observations. The effects of the soil, crop and climate conditions tested in this work were less important than those of cropping practices. STICS-MACRO allows an ex ante evaluation of cropping systems and agricultural practices, and of the related pesticides environmental impacts. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

    Science.gov (United States)

    Klein, Alison P; Wolpin, Brian M; Risch, Harvey A; Stolzenberg-Solomon, Rachael Z; Mocci, Evelina; Zhang, Mingfeng; Canzian, Federico; Childs, Erica J; Hoskins, Jason W; Jermusyk, Ashley; Zhong, Jun; Chen, Fei; Albanes, Demetrius; Andreotti, Gabriella; Arslan, Alan A; Babic, Ana; Bamlet, William R; Beane-Freeman, Laura; Berndt, Sonja I; Blackford, Amanda; Borges, Michael; Borgida, Ayelet; Bracci, Paige M; Brais, Lauren; Brennan, Paul; Brenner, Hermann; Bueno-de-Mesquita, Bas; Buring, Julie; Campa, Daniele; Capurso, Gabriele; Cavestro, Giulia Martina; Chaffee, Kari G; Chung, Charles C; Cleary, Sean; Cotterchio, Michelle; Dijk, Frederike; Duell, Eric J; Foretova, Lenka; Fuchs, Charles; Funel, Niccola; Gallinger, Steven; M Gaziano, J Michael; Gazouli, Maria; Giles, Graham G; Giovannucci, Edward; Goggins, Michael; Goodman, Gary E; Goodman, Phyllis J; Hackert, Thilo; Haiman, Christopher; Hartge, Patricia; Hasan, Manal; Hegyi, Peter; Helzlsouer, Kathy J; Herman, Joseph; Holcatova, Ivana; Holly, Elizabeth A; Hoover, Robert; Hung, Rayjean J; Jacobs, Eric J; Jamroziak, Krzysztof; Janout, Vladimir; Kaaks, Rudolf; Khaw, Kay-Tee; Klein, Eric A; Kogevinas, Manolis; Kooperberg, Charles; Kulke, Matthew H; Kupcinskas, Juozas; Kurtz, Robert J; Laheru, Daniel; Landi, Stefano; Lawlor, Rita T; Lee, I-Min; LeMarchand, Loic; Lu, Lingeng; Malats, Núria; Mambrini, Andrea; Mannisto, Satu; Milne, Roger L; Mohelníková-Duchoňová, Beatrice; Neale, Rachel E; Neoptolemos, John P; Oberg, Ann L; Olson, Sara H; Orlow, Irene; Pasquali, Claudio; Patel, Alpa V; Peters, Ulrike; Pezzilli, Raffaele; Porta, Miquel; Real, Francisco X; Rothman, Nathaniel; Scelo, Ghislaine; Sesso, Howard D; Severi, Gianluca; Shu, Xiao-Ou; Silverman, Debra; Smith, Jill P; Soucek, Pavel; Sund, Malin; Talar-Wojnarowska, Renata; Tavano, Francesca; Thornquist, Mark D; Tobias, Geoffrey S; Van Den Eeden, Stephen K; Vashist, Yogesh; Visvanathan, Kala; Vodicka, Pavel; Wactawski-Wende, Jean; Wang, Zhaoming; Wentzensen, Nicolas; White, Emily; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Kraft, Peter; Li, Donghui; Chanock, Stephen; Obazee, Ofure; Petersen, Gloria M; Amundadottir, Laufey T

    2018-02-08

    In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10 -8 ). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10 -14 ), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10 -10 ), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10 -8 ), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10 -8 ). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.

  18. Probabilistic Latent Semantic Analysis Applied to Whole Bacterial Genomes Identifies Common Genomic Features

    Directory of Open Access Journals (Sweden)

    Rusakovica J.

    2014-06-01

    Full Text Available The spread of drug resistance amongst clinically-important bacteria is a serious, and growing, problem [1]. However, the analysis of entire genomes requires considerable computational effort, usually including the assembly of the genome and subsequent identification of genes known to be important in pathology. An alternative approach is to use computational algorithms to identify genomic differences between pathogenic and non-pathogenic bacteria, even without knowing the biological meaning of those differences. To overcome this problem, a range of techniques for dimensionality reduction have been developed. One such approach is known as latent-variable models [2]. In latent-variable models dimensionality reduction is achieved by representing a high-dimensional data by a few hidden or latent variables, which are not directly observed but inferred from the observed variables present in the model. Probabilistic Latent Semantic Indexing (PLSA is an extention of LSA [3]. PLSA is based on a mixture decomposition derived from a latent class model. The main objective of the algorithm, as in LSA, is to represent high-dimensional co-occurrence information in a lower-dimensional way in order to discover the hidden semantic structure of the data using a probabilistic framework.

  19. Identifying indicators of harmful and problem gambling in a Canadian sample through receiver operating characteristic analysis.

    Science.gov (United States)

    Quilty, Lena C; Avila Murati, Daniela; Bagby, R Michael

    2014-03-01

    Many gamblers would prefer to reduce gambling on their own rather than to adopt an abstinence approach within the context of a gambling treatment program. Yet responsible gambling guidelines lack quantifiable markers to guide gamblers in wagering safely. To address these issues, the current investigation implemented receiver operating characteristic (ROC) analysis to identify behavioral indicators of harmful and problem gambling. Gambling involvement was assessed in 503 participants (275 psychiatric outpatients and 228 community gamblers) with the Canadian Problem Gambling Index. Overall gambling frequency, duration, and expenditure were able to distinguish harmful and problematic gambling at a moderate level. Indicators of harmful gambling were generated for engagement in specific gambling activities: frequency of tickets and casino; duration of bingo, casino, and investments; and expenditures on bingo, casino, sports betting, games of skill, and investments. Indicators of problem gambling were similarly produced for frequency of tickets and casino, and expenditures on bingo, casino, games of skill, and investments. Logistic regression analyses revealed that overall gambling frequency uniquely predicted the presence of harmful and problem gambling. Furthermore, frequency indicators for tickets and casino uniquely predicted the presence of both harmful and problem gambling. Together, these findings contribute to the development of an empirically based method enabling the minimization of harmful or problem gambling through self-control rather than abstinence.

  20. Toward the Analysis of JWST Exoplanet Spectra: Identifying Troublesome Model Parameters

    Science.gov (United States)

    Baudino, Jean-Loup; Mollière, Paul; Venot, Olivia; Tremblin, Pascal; Bézard, Bruno; Lagage, Pierre-Olivier

    2017-12-01

    Given the forthcoming launch of the James Webb Space Telescope (JWST), which will allow observing exoplanet atmospheres with unprecedented signal-to-noise ratio, spectral coverage, and spatial resolution, the uncertainties in the atmosphere modeling used to interpret the data need to be assessed. As the first step, we compare three independent 1D radiative-convective models: ATMO, Exo-REM, and petitCODE. We identify differences in physical and chemical processes that are taken into account thanks to a benchmark protocol we have developed. We study the impact of these differences on the analysis of observable spectra. We show the importance of selecting carefully relevant molecular linelists to compute the atmospheric opacity. Indeed, differences between spectra calculated with Hitran and ExoMol exceed the expected uncertainties of future JWST observations. We also show the limits of the precision of the models due to uncertainties on alkali and molecule lineshape, which induce spectral effects that are also larger than the expected JWST uncertainties. We compare two chemical models, Exo-REM and Venot Chemical Code, which do not lead to significant differences in the emission or transmission spectra. We discuss the observational consequences of using equilibrium or out-of-equilibrium chemistry and the major impact of phosphine, detectable with the JWST. Each of the models has benefited from the benchmarking activity and has been updated. The protocol developed in this paper and the online results can constitute a test case for other models.

  1. Genome wide transcriptome analysis of dendritic cells identifies genes with altered expression in psoriasis.

    Directory of Open Access Journals (Sweden)

    Kata Filkor

    Full Text Available Activation of dendritic cells by different pathogens induces the secretion of proinflammatory mediators resulting in local inflammation. Importantly, innate immunity must be properly controlled, as its continuous activation leads to the development of chronic inflammatory diseases such as psoriasis. Lipopolysaccharide (LPS or peptidoglycan (PGN induced tolerance, a phenomenon of transient unresponsiveness of cells to repeated or prolonged stimulation, proved valuable model for the study of chronic inflammation. Thus, the aim of this study was the identification of the transcriptional diversity of primary human immature dendritic cells (iDCs upon PGN induced tolerance. Using SAGE-Seq approach, a tag-based transcriptome sequencing method, we investigated gene expression changes of primary human iDCs upon stimulation or restimulation with Staphylococcus aureus derived PGN, a widely used TLR2 ligand. Based on the expression pattern of the altered genes, we identified non-tolerizeable and tolerizeable genes. Gene Ontology (GO and Kyoto Encyclopedia of Genes and Genomes (Kegg analysis showed marked enrichment of immune-, cell cycle- and apoptosis related genes. In parallel to the marked induction of proinflammatory mediators, negative feedback regulators of innate immunity, such as TNFAIP3, TNFAIP8, Tyro3 and Mer are markedly downregulated in tolerant cells. We also demonstrate, that the expression pattern of TNFAIP3 and TNFAIP8 is altered in both lesional, and non-lesional skin of psoriatic patients. Finally, we show that pretreatment of immature dendritic cells with anti-TNF-α inhibits the expression of IL-6 and CCL1 in tolerant iDCs and partially releases the suppression of TNFAIP8. Our findings suggest that after PGN stimulation/restimulation the host cell utilizes different mechanisms in order to maintain critical balance between inflammation and tolerance. Importantly, the transcriptome sequencing of stimulated/restimulated iDCs identified

  2. Microarray analysis identifies a common set of cellular genes modulated by different HCV replicon clones

    Directory of Open Access Journals (Sweden)

    Gerosolimo Germano

    2008-06-01

    Full Text Available Abstract Background Hepatitis C virus (HCV RNA synthesis and protein expression affect cell homeostasis by modulation of gene expression. The impact of HCV replication on global cell transcription has not been fully evaluated. Thus, we analysed the expression profiles of different clones of human hepatoma-derived Huh-7 cells carrying a self-replicating HCV RNA which express all viral proteins (HCV replicon system. Results First, we compared the expression profile of HCV replicon clone 21-5 with both the Huh-7 parental cells and the 21-5 cured (21-5c cells. In these latter, the HCV RNA has been eliminated by IFN-α treatment. To confirm data, we also analyzed microarray results from both the 21-5 and two other HCV replicon clones, 22-6 and 21-7, compared to the Huh-7 cells. The study was carried out by using the Applied Biosystems (AB Human Genome Survey Microarray v1.0 which provides 31,700 probes that correspond to 27,868 human genes. Microarray analysis revealed a specific transcriptional program induced by HCV in replicon cells respect to both IFN-α-cured and Huh-7 cells. From the original datasets of differentially expressed genes, we selected by Venn diagrams a final list of 38 genes modulated by HCV in all clones. Most of the 38 genes have never been described before and showed high fold-change associated with significant p-value, strongly supporting data reliability. Classification of the 38 genes by Panther System identified functional categories that were significantly enriched in this gene set, such as histones and ribosomal proteins as well as extracellular matrix and intracellular protein traffic. The dataset also included new genes involved in lipid metabolism, extracellular matrix and cytoskeletal network, which may be critical for HCV replication and pathogenesis. Conclusion Our data provide a comprehensive analysis of alterations in gene expression induced by HCV replication and reveal modulation of new genes potentially useful

  3. Tissue-type-specific transcriptome analysis identifies developing xylem-specific promoters in poplar.

    Science.gov (United States)

    Ko, Jae-Heung; Kim, Hyun-Tae; Hwang, Ildoo; Han, Kyung-Hwan

    2012-06-01

    Plant biotechnology offers a means to create novel phenotypes. However, commercial application of biotechnology in crop improvement programmes is severely hindered by the lack of utility promoters (or freedom to operate the existing ones) that can drive gene expression in a tissue-specific or temporally controlled manner. Woody biomass is gaining popularity as a source of fermentable sugars for liquid fuel production. To improve the quantity and quality of woody biomass, developing xylem (DX)-specific modification of the feedstock is highly desirable. To develop utility promoters that can drive transgene expression in a DX-specific manner, we used the Affymetrix Poplar Genome Arrays to obtain tissue-type-specific transcriptomes from poplar stems. Subsequent bioinformatics analysis identified 37 transcripts that are specifically or strongly expressed in DX cells of poplar. After further confirmation of their DX-specific expression using semi-quantitative PCR, we selected four genes (DX5, DX8, DX11 and DX15) for in vivo confirmation of their tissue-specific expression in transgenic poplars. The promoter regions of the selected DX genes were isolated and fused to a β-glucuronidase (GUS)-reported gene in a binary vector. This construct was used to produce transgenic poplars via Agrobacterium-mediated transformation. The GUS expression patterns of the resulting transgenic plants showed that these promoters were active in the xylem cells at early seedling growth and had strongest expression in the developing xylem cells at later growth stages of poplar. We conclude that these DX promoters can be used as a utility promoter for DX-specific biomass engineering. © 2012 The Authors. Plant Biotechnology Journal © 2012 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  4. Novel Host Proteins and Signaling Pathways in Enteropathogenic E. coli Pathogenesis Identified by Global Phosphoproteome Analysis*

    Science.gov (United States)

    Scholz, Roland; Imami, Koshi; Scott, Nichollas E.; Trimble, William S.; Foster, Leonard J.; Finlay, B. Brett

    2015-01-01

    Enteropathogenic Escherichia coli (EPEC) uses a type III secretion system (T3SS) to directly translocate effector proteins into host cells where they play a pivotal role in subverting host cell signaling needed for disease. However, our knowledge of how EPEC affects host protein phosphorylation is limited to a few individual protein studies. We employed a quantitative proteomics approach to globally map alterations in the host phosphoproteome during EPEC infection. By characterizing host phosphorylation events at various time points throughout infection, we examined how EPEC dynamically impacts the host phosphoproteome over time. This experimental setup also enabled identification of T3SS-dependent and -independent changes in host phosphorylation. Specifically, T3SS-regulated events affected various cellular processes that are known EPEC targets, including cytoskeletal organization, immune signaling, and intracellular trafficking. However, the involvement of phosphorylation in these events has thus far been poorly studied. We confirmed the MAPK family as an established key host player, showed its central role in signal transduction during EPEC infection, and extended the repertoire of known signaling hubs with previously unrecognized proteins, including TPD52, CIN85, EPHA2, and HSP27. We identified altered phosphorylation of known EPEC targets, such as cofilin, where the involvement of phosphorylation has so far been undefined, thus providing novel mechanistic insights into the roles of these proteins in EPEC infection. An overlap of regulated proteins, especially those that are cytoskeleton-associated, was observed when compared with the phosphoproteome of Shigella-infected cells. We determined the biological relevance of the phosphorylation of a novel protein in EPEC pathogenesis, septin-9 (SEPT9). Both siRNA knockdown and a phosphorylation-impaired SEPT9 mutant decreased bacterial adherence and EPEC-mediated cell death. In contrast, a phosphorylation

  5. Transcriptome Analysis of Syringa oblata Lindl. Inflorescence Identifies Genes Associated with Pigment Biosynthesis and Scent Metabolism.

    Directory of Open Access Journals (Sweden)

    Jian Zheng

    Full Text Available Syringa oblata Lindl. is a woody ornamental plant with high economic value and characteristics that include early flowering, multiple flower colors, and strong fragrance. Despite a long history of cultivation, the genetics and molecular biology of S. oblata are poorly understood. Transcriptome and expression profiling data are needed to identify genes and to better understand the biological mechanisms of floral pigments and scents in this species. Nine cDNA libraries were obtained from three replicates of three developmental stages: inflorescence with enlarged flower buds not protruded, inflorescence with corolla lobes not displayed, and inflorescence with flowers fully opened and emitting strong fragrance. Using the Illumina RNA-Seq technique, 319,425,972 clean reads were obtained and were assembled into 104,691 final unigenes (average length of 853 bp, 41.75% of which were annotated in the NCBI non-redundant protein database. Among the annotated unigenes, 36,967 were assigned to gene ontology categories and 19,956 were assigned to eukaryoticorthologous groups. Using the Kyoto Encyclopedia of Genes and Genomes pathway database, 12,388 unigenes were sorted into 286 pathways. Based on these transcriptomic data, we obtained a large number of candidate genes that were differentially expressed at different flower stages and that were related to floral pigment biosynthesis and fragrance metabolism. This comprehensive transcriptomic analysis provides fundamental information on the genes and pathways involved in flower secondary metabolism and development in S. oblata, providing a useful database for further research on S. oblata and other plants of genus Syringa.

  6. Development of a sandwich ELISA for the thrombin light chain identified by serum proteome analysis

    Directory of Open Access Journals (Sweden)

    Kazuyuki Sogawa

    2017-08-01

    Full Text Available We previously identified novel biomarker candidates in biliary tract cancer (BTC using serum proteome analysis. Among several candidates, we focused on thrombin light chain which is a 4204 Da peptide as the most promising biomarker for BTC. To move thrombin light chain toward potential diagnostic use, we developed an enzyme immunoassay that enables to measure serum thrombin light chain levels.Both one monoclonal antibody specific to the N-termini and one polyclonal antibody were used to develop a sandwich ELISA for thrombin light chain. The assay was evaluated by comparing the results with those obtained by the ClinProt™ system. Serum samples were obtained from 20 patients with BTC, 20 patients with BBTDs and 20 HVs using the ClinProt™ system and ELISA.The results of the established ELISA showed a positive correlation with the findings by ClinProt™ system (slope=0.3386, intercept=34.901, r2=0.9641. The performance of the ELISA was satisfactory in terms of recovery (97.9–102.5% and within-run (1.5–4.8% and between-day (1.9–6.7% reproducibility. Serum thrombin light chain levels were significantly greater in BTC (176.5±47.2 ng/mL than in BBTDs (128.6±17.4 ng/mL and HVs (127.6±16.0 ng/mL (p<0.001.The sandwich ELISA developed in this study will be useful for validation of the diagnostic significance of serum thrombin light chain levels in various cancers. Keywords: Thrombin light chain, Biliary tract cancer, Sandwich ELISA, Serum biomarker

  7. Prognostically distinct clinical patterns of systemic lupus erythematosus identified by cluster analysis.

    Science.gov (United States)

    To, C H; Mok, C C; Tang, S S K; Ying, S K Y; Wong, R W S; Lau, C S

    2009-12-01

    The objective of this study was to evaluate the patterns of clinical manifestations and their mortality in a large cohort of Chinese patients with systemic lupus erythematosus. The cumulative clinical manifestations of a large group of Chinese systemic lupus erythematosus patients who fulfilled at least four American College of Rheumatology criteria for systemic lupus erythematosus were studied. Patients were divided into distinct groups by using the K-mean cluster analysis. Clinical features, prevalence of proliferative lupus nephritis (World Health Organization class III, IV), autoantibody profile, and treatment data were compared and the standardized mortality ratios were calculated for each cluster of patients. There were 1082 patients included in the study (mean age at systemic lupus erythematosus diagnosis 30.5 years; mean systemic lupus erythematosus duration 10.3 years). Three distinct groups of patients were identified. Cluster 1 (n = 347) was characterized predominantly by mucocutaneous manifestations (malar rash, discoid rash, photosensitivity, oral ulcer) and arthritis but having the lowest prevalence of serositis, hematologic manifestations (hemolytic anemia, leukopenia, and thrombocytopenia), and proliferative lupus nephritis. Patients in cluster 2 (n = 409) had mainly renal and hematological manifestations but having the lowest prevalence of mucocutaneous manifestations. Pulmonary and gastrointestinal manifestations were significantly more frequent in cluster 2 than the other clusters. Cluster 3 patients (n = 326) had the most heterogeneous features. Besides having a high prevalence of mucocutaneous manifestations, serositis and hematologic manifestations, renal involvement, and proliferative lupus nephritis was also most prevalent among the three clusters. Patients in cluster 2 had a much higher standardized mortality ratio [standardized mortality ratio 7.23 (6.7-7.7), p lupus erythematosus could be clustered into prognostically distinct patterns of

  8. [Neonaticides in France: analysis of 357 cases identified in the press (1993-2012)].

    Science.gov (United States)

    Simmat-Durand, Laurence

    2017-07-10

    Background and objectives: Despite easy access to contraception and child abandonment in France, neonaticides continue to occur and, although rare, are widely publicized. The objective of this study was to characterize neonaticides and their perpetrators over a twenty-year period in France based on cases reported in the press. Methods: 2,319 press articles describing the discovery of a newborn corpse in the regional and national press were extracted from electronic databases or other digital supports. A total of 357 neonaticides were described, corresponding to a mean annual rate of 2.34 per 100,000 births. Results: The mother was identified in 74% of cases. The corpse was usually discovered in the house or garden (35%, mostly in the rubbish bin and 6% in the freezer), but also in the wilds (31%). In almost one-quarter of cases, the mother had suffered a haemorrhage. Most neonates were killed by asphyxiation (35%), direct blows or being thrown out of a window (11%), or drowning (11%). Only 22% of neonates died without the mother’s intervention, due to lack of care or neglect. Marked regional disparities were observed, even after calculation of regional rates. The mothers responsible (230 women due to 19 multiple neonaticides) had a mean age of 27.8 years and half of them had at least one other living child. Conclusions: Media coverage of neonaticides and access to electronic databases provide an opportunity to describe a rare phenomenon, for which it is difficult to collect sufficient sample sizes to allow analysis of the perpetrators and court rulings.

  9. Genomewide copy number analysis of Müllerian adenosarcoma identified chromosomal instability in the aggressive subgroup.

    Science.gov (United States)

    Lee, Jen-Chieh; Lu, Tzu-Pin; Changou, Chun A; Liang, Cher-Wei; Huang, Hsien-Neng; Lauria, Alexandra; Huang, Hsuan-Ying; Lin, Chin-Yao; Chiang, Ying-Cheng; Davidson, Ben; Lin, Ming-Chieh; Kuo, Kuan-Ting

    2016-09-01

    Müllerian adenosarcomas are malignant gynecologic neoplasms. Advanced staging and sarcomatous overgrowth predict poor prognosis. Because the genomic landscape remains poorly understood, we conducted this study to characterize the genomewide copy number variations in adenosarcomas. Sixteen tumors, including eight with and eight without sarcomatous overgrowth, were subjected to a molecular inversion probe array analysis. Copy number variations, particularly losses, were significantly higher in cases with sarcomatous overgrowth. Frequent gains of chromosomal 12q were noted, often involving cancer-associated genes CDK4 (six cases), MDM2, CPM, YEATS4, DDIT3, GLI1 (five each), HMGA2 and STAT6 (four), without association with sarcomatous overgrowth status. The most frequent losses involved chromosomes 13q (five cases), 9p, 16q and 17q (four cases each) and were almost limited to cases with sarcomatous overgrowth. MDM2 and CDK4 amplification, as well as losses of RB1 (observed in two cases) and CDKN2A/B (one case), was verified by FISH. By immunohistochemistry, all MDM2/CDK4-coamplified cases were confirmed to overexpress both encoded proteins, whereas all four cases with (plus an additional four without) gain of HMGA2 overexpressed the HMGA2 protein. Both cases with RB1 loss were negative for the immunostaining of the encoded protein. Chromothripsis-like copy number profiles involving chromosome 12 or 14 were observed in three fatal cases, all of which harbored sarcomatous overgrowth. With whole chromosome painting and deconvolution fluorescent microscopy, dividing tumor cells in all three cases were shown to have scattered extrachromosomal materials derived from chromosomes involved by chromothripsis, suggesting that this phenomenon may serve as visual evidence for chromothripsis in paraffin tissue. In conclusion, we identified frequent chromosome 12q amplifications, including loci containing potential pharmacological targets. Global chromosomal instability and

  10. Potential Coastal Pumped Hydroelectric Energy Storage Locations Identified using GIS-based Topographic Analysis

    Science.gov (United States)

    Parsons, R.; Barnhart, C. J.; Benson, S. M.

    2013-12-01

    Large-scale electrical energy storage could accommodate variable, weather dependent energy resources such as wind and solar. Pumped hydroelectric energy storage (PHS) and compressed energy storage area (CAES) have life cycle energy and financial costs that are an order of magnitude lower than conventional electrochemical storage technologies. However PHS and CAES storage technologies require specific geologic conditions. Conventional PHS requires an upper and lower reservoir separated by at least 100 m of head, but no more than 10 km in horizontal distance. Conventional PHS also impacts fresh water supplies, riparian ecosystems, and hydrologic environments. A PHS facility that uses the ocean as the lower reservoir benefits from a smaller footprint, minimal freshwater impact, and the potential to be located near off shore wind resources and population centers. Although technologically nascent, today one coastal PHS facility exists. The storage potential for coastal PHS is unknown. Can coastal PHS play a significant role in augmenting future power grids with a high faction of renewable energy supply? In this study we employ GIS-based topographic analysis to quantify the coastal PHS potential of several geographic locations, including California, Chile and Peru. We developed automated techniques that seek local topographic minima in 90 m spatial resolution shuttle radar topography mission (SRTM) digital elevation models (DEM) that satisfy the following criteria conducive to PHS: within 10 km from the sea; minimum elevation 150 m; maximum elevation 1000 m. Preliminary results suggest the global potential for coastal PHS could be very significant. For example, in northern Chile we have identified over 60 locations that satisfy the above criteria. Two of these locations could store over 10 million cubic meters of water or several GWh of energy. We plan to report a global database of candidate coastal PHS locations and to estimate their energy storage capacity.

  11. Identifying Natural syNergist from Pongamia pinnata Using High-Speed Counter-Current Chromatography Combined with Isobolographic Analysis

    Directory of Open Access Journals (Sweden)

    Hao Yin

    2017-03-01

    Full Text Available For identifying the synergistic compounds from Pongamia pinnata, an approach based on high-speed counter-current chromatography (HSCCC combined with isobolographic analysis was designed to detect the synergistic effects in the complex mixture [...

  12. Spatial and temporal variability of seawater properties, current velocity and SPM concentration off Cassino Beach-Rio Grande-Southern Brazil

    DEFF Research Database (Denmark)

    Guerra, J. V.; Azevedo, M. M.; Esteves, L. S.

    2009-01-01

    Water column profiles and near-bed time series of pressure, current velocity, suspended-particulate matter (SPM) concentration and seawater temperature and salinity were collected during three short cruises carried out in May 2005 in the shoreface and inner shelf area adjacent to Cassino Beach...... of 13.8 was measured at similar to 10 km from the coast. Four days later, no trace of the plume was detected in the area. Regarding seawater temperature, no large temporal or spatial variability was documented with measured values ranging from 19.3 to 20 degrees C. Water column currents were prominently...

  13. A genetic and genomic analysis identifies a cluster of genes associated with hematopoietic cell turnover

    NARCIS (Netherlands)

    de Haan, G; Bystrykh, LV; Weersing, E; Dontje, B; Geiger, H; Ivanova, N; Lemischka, IR; Vellenga, E; Van Zant, G

    2002-01-01

    Hematopoietic stem cells from different strains of mice vary widely with respect to their cell cycle activity. In the present study we used complementary genetic and genomic approaches to identify molecular pathways affecting this complex trait. We identified a major quantitative trait locus (QTL)

  14. Novel Host Proteins and Signaling Pathways in Enteropathogenic E. coli Pathogenesis Identified by Global Phosphoproteome Analysis.

    Science.gov (United States)

    Scholz, Roland; Imami, Koshi; Scott, Nichollas E; Trimble, William S; Foster, Leonard J; Finlay, B Brett

    2015-07-01

    Enteropathogenic Escherichia coli (EPEC) uses a type III secretion system (T3SS) to directly translocate effector proteins into host cells where they play a pivotal role in subverting host cell signaling needed for disease. However, our knowledge of how EPEC affects host protein phosphorylation is limited to a few individual protein studies. We employed a quantitative proteomics approach to globally map alterations in the host phosphoproteome during EPEC infection. By characterizing host phosphorylation events at various time points throughout infection, we examined how EPEC dynamically impacts the host phosphoproteome over time. This experimental setup also enabled identification of T3SS-dependent and -independent changes in host phosphorylation. Specifically, T3SS-regulated events affected various cellular processes that are known EPEC targets, including cytoskeletal organization, immune signaling, and intracellular trafficking. However, the involvement of phosphorylation in these events has thus far been poorly studied. We confirmed the MAPK family as an established key host player, showed its central role in signal transduction during EPEC infection, and extended the repertoire of known signaling hubs with previously unrecognized proteins, including TPD52, CIN85, EPHA2, and HSP27. We identified altered phosphorylation of known EPEC targets, such as cofilin, where the involvement of phosphorylation has so far been undefined, thus providing novel mechanistic insights into the roles of these proteins in EPEC infection. An overlap of regulated proteins, especially those that are cytoskeleton-associated, was observed when compared with the phosphoproteome of Shigella-infected cells. We determined the biological relevance of the phosphorylation of a novel protein in EPEC pathogenesis, septin-9 (SEPT9). Both siRNA knockdown and a phosphorylation-impaired SEPT9 mutant decreased bacterial adherence and EPEC-mediated cell death. In contrast, a phosphorylation

  15. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

    DEFF Research Database (Denmark)

    Beecham, Ashley H; Patsopoulos, Nikolaos A; Xifara, Dionysia K

    2013-01-01

    Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P...

  16. Identifying the relevant features of the National Digital Cadastral Database (NDCDB) for spatial analysis by using the Delphi Technique

    Science.gov (United States)

    Halim, N. Z. A.; Sulaiman, S. A.; Talib, K.; Ng, E. G.

    2018-02-01

    This paper explains the process carried out in identifying the relevant features of the National Digital Cadastral Database (NDCDB) for spatial analysis. The research was initially a part of a larger research exercise to identify the significance of NDCDB from the legal, technical, role and land-based analysis perspectives. The research methodology of applying the Delphi technique is substantially discussed in this paper. A heterogeneous panel of 14 experts was created to determine the importance of NDCDB from the technical relevance standpoint. Three statements describing the relevant features of NDCDB for spatial analysis were established after three rounds of consensus building. It highlighted the NDCDB’s characteristics such as its spatial accuracy, functions, and criteria as a facilitating tool for spatial analysis. By recognising the relevant features of NDCDB for spatial analysis in this study, practical application of NDCDB for various analysis and purpose can be widely implemented.

  17. Petri net siphon analysis and graph theoretic measures for identifying combination therapies in cancer.

    Science.gov (United States)

    Behinaein, Behnam; Rudie, Karen; Sangrar, Waheed

    2016-10-03

    Epidermal Growth Factor Receptor (EGFR) signaling to the Ras-MAPK pathway is implicated in the development and progression of cancer and is a major focus of targeted combination therapies. Physiochemical models have been used for identifying and testing the signal-inhibiting potential of targeted therapies, however, their application to larger multi-pathway networks is limited by the availability of experimentally-determined rate and concentration parameters. An alternate strategy for identifying and evaluating drug-targetable nodes is proposed. A physiochemical model of EGFR-Ras-MAPK signaling is implemented and calibrated to experimental data. Essential topological features of the model are converted into a Petri net and nodes that behave as siphons-a structural property of Petri nets-are identified. Siphons represent potential drug-targets since they are unrecoverable if their values fall below a threshold. Centrality measures are then used to prioritize siphons identified as candidate drug-targets. Single and multiple drug-target combinations are identified which correspond to clinically relevant drug targets and exhibit inhibition synergy in physiochemical simulations of EGF-induced EGFR-Ras-MAPK signaling. Taken together, these studies suggest that siphons and centrality analyses are a promising computational strategy to identify and rank drug-targetable nodes in larger networks as they do not require knowledge of the dynamics of the system, but rely solely on topology.

  18. Search Strategy to Identify Dental Survival Analysis Articles Indexed in MEDLINE.

    Science.gov (United States)

    Layton, Danielle M; Clarke, Michael

    2016-01-01

    Articles reporting survival outcomes (time-to-event outcomes) in patients over time are challenging to identify in the literature. Research shows the words authors use to describe their dental survival analyses vary, and that allocation of medical subject headings by MEDLINE indexers is inconsistent. Together, this undermines accurate article identification. The present study aims to develop and validate a search strategy to identify dental survival analyses indexed in MEDLINE (Ovid). A gold standard cohort of articles was identified to derive the search terms, and an independent gold standard cohort of articles was identified to test and validate the proposed search strategies. The first cohort included all 6,955 articles published in the 50 dental journals with the highest impact factors in 2008, of which 95 articles were dental survival articles. The second cohort included all 6,514 articles published in the 50 dental journals with the highest impact factors for 2012, of which 148 were dental survival articles. Each cohort was identified by a systematic hand search. Performance parameters of sensitivity, precision, and number needed to read (NNR) for the search strategies were calculated. Sensitive, precise, and optimized search strategies were developed and validated. The performances of the search strategy maximizing sensitivity were 92% sensitivity, 14% precision, and 7.11 NNR; the performances of the strategy maximizing precision were 93% precision, 10% sensitivity, and 1.07 NNR; and the performances of the strategy optimizing the balance between sensitivity and precision were 83% sensitivity, 24% precision, and 4.13 NNR. The methods used to identify search terms were objective, not subjective. The search strategies were validated in an independent group of articles that included different journals and different publication years. Across the three search strategies, dental survival articles can be identified with sensitivity up to 92%, precision up to 93

  19. Identifying airline cost economies: An econometric analysis of the factors affecting aircraft opeerating costs

    NARCIS (Netherlands)

    Zuidberg, J.

    2014-01-01

    This paper provides the results of an econometric analysis of the influences of airline characteristics on the average operating costs per aircraft movement. The analysis combines a comprehensive selection of airline-output variables, airline-fleet variables, and airline-market variables. The

  20. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease

    NARCIS (Netherlands)

    H. Schunkert (Heribert); I.R. König (Inke); S. Kathiresan (Sekar); M.P. Reilly (Muredach); T.L. Assimes (Themistocles); H. Holm (Hilma); M. Preuss (Michael); A.F.R. Stewart (Alexandre); M. Barbalic (maja); C. Gieger (Christian); D. Absher (Devin); Z. Aherrahrou (Zouhair); H. Allayee (Hooman); D. Altshuler (David); S.S. Anand (Sonia); K.K. Andersen (Karl); J.L. Anderson (Jeffrey); D. Ardissino (Diego); S.G. Ball (Stephen); A.J. Balmforth (Anthony); T.A. Barnes (Timothy); D.M. Becker (Diane); K. Berger (Klaus); J.C. Bis (Joshua); S.M. Boekholdt (Matthijs); E.A. Boerwinkle (Eric); P.S. Braund (Peter); M.J. Brown (Morris); M.S. Burnett; I. Buysschaert (Ian); J.F. Carlquist (John); L. Chen (Li); S. Cichon (Sven); V. Codd (Veryan); R.W. Davies (Robert); G.V. Dedoussis (George); A. Dehghan (Abbas); S. Demissie (Serkalem); J. Devaney (Joseph); P. Diemert (Patrick); R. Do (Ron); A. Doering (Angela); S. Eifert (Sandra); N.E.E. Mokhtari; S.G. Ellis (Stephen); R. Elosua (Roberto); J.C. Engert (James); S.E. Epstein (Stephen); U. de Faire (Ulf); M. Fischer (Marcus); A.R. Folsom (Aaron); J. Freyer (Jennifer); B. Gigante (Bruna); D. Girelli (Domenico); S. Gretarsdottir (Solveig); V. Gudnason (Vilmundur); J.R. Gulcher (Jeffrey); E. Halperin (Eran); N. Hammond (Naomi); S.L. Hazen (Stanley); A. Hofman (Albert); B.D. Horne (Benjamin); T. Illig (Thomas); C. Iribarren (Carlos); G.T. Jones (Gregory); J.W. Jukema (Jan Wouter); M.A. Kaiser (Michael); R.C. Kaplan (Robert); K-T. Khaw (Kay-Tee); J.W. Knowles (Joshua); G. Kolovou (Genovefa); A. Kong (Augustine); R. Laaksonen (Reijo); D. Lambrechts (Diether); K. Leander (Karin); G. Lettre (Guillaume); X. Li (Xiaohui); W. Lieb (Wolfgang); C. Loley (Christina); A.J. Lotery (Andrew); P.M. Mannucci (Pier); S. Maouche (Seraya); N. Martinelli (Nicola); P.P. McKeown (Pascal); C. Meisinger (Christa); T. Meitinger (Thomas); O. Melander (Olle); P.A. Merlini; V. Mooser (Vincent); T. Morgan (Thomas); T.W. Mühleisen (Thomas); J.B. Muhlestein (Joseph); T. Münzel (Thomas); K. Musunuru (Kiran); J. Nahrstaedt (Janja); C.P. Nelson (Christopher P.); M.M. Nöthen (Markus); O. Olivieri (Oliviero); R.S. Patel (Riyaz); C.C. Patterson (Chris); A. Peters (Annette); F. Peyvandi (Flora); L. Qu (Liming); A.A. Quyyumi (Arshed); D.J. Rader (Daniel); L.S. Rallidis (Loukianos); C. Rice (Catherine); F.R. Rosendaal (Frits); D. Rubin (Diana); V. Salomaa (Veikko); M.L. Sampietro (Maria Lourdes); M.S. Sandhu (Manj); E.E. Schadt (Eric); A. Scḧsignfer (Arne); A. Schillert (Arne); S. Schreiber (Stefan); J. Schrezenmeir (Jürgen); S.M. Schwartz (Stephen); D.S. Siscovick (David); M. Sivananthan (Mohan); S. Sivapalaratnam (Suthesh); A.V. Smith (Albert Vernon); J.D. Snoep (Jaapjan); N. Soranzo (Nicole); J.A. Spertus (John); K. Stark (Klaus); K. Stirrups (Kathy); M. Stoll (Monika); W.H.W. Tang (Wilson); S. Tennstedt (Stephanie); G. Thorgeirsson (Gudmundur); G. Thorleifsson (Gudmar); M. Tomaszewski (Maciej); A.G. Uitterlinden (André); A.M. van Rij (Andre); B.F. Voight (Benjamin); N.J. Wareham (Nick); G.A. Wells (George); H.E. Wichmann (Heinz Erich); P.S. Wild (Philipp); C. Willenborg (Christina); J.C.M. Witteman (Jacqueline); B.J. Wright (Benjamin); S. Ye (Shu); T. Zeller (Tanja); A. Ziegler (Andreas); F. Cambien (François); A.H. Goodall (Alison); L.A. Cupples (Adrienne); T. Quertermous (Thomas); W. Mäsignrz (Winfried); C. Hengstenberg (Christian); S. Blankenberg (Stefan); W.H. Ouwehand (Willem); A.S. Hall (Alistair); J.J.P. Kastelein (John); P. Deloukas (Panagiotis); J.R. Thompson (John); K. Stefansson (Kari); R. Roberts (Robert); U. Thorsteinsdottir (Unnur); C.J. O'Donnell (Christopher); R. McPherson (Ruth); J. Erdmann (Jeanette); N.J. Samani (Nilesh)

    2011-01-01

    textabstractWe performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis

  1. Short communication: Practical issues in implementing volatile metabolite analysis for identifying mastitis pathogens

    NARCIS (Netherlands)

    Hettinga, K.A.; Bok, de F.A.M.; Lam, T.

    2015-01-01

    Several parameters for improving volatile metabolite analysis using headspace gas chromatography-mass spectrometry (GC-MS) analysis of volatile metabolites were evaluated in the framework of identification of mastitis-causing pathogens. Previous research showed that the results of such volatile

  2. Short communication : Practical issues in implementing volatile metabolite analysis for identifying mastitis pathogens

    NARCIS (Netherlands)

    Hettinga, Kasper A; de Bok, Frank A M; Lam, Theo J G M

    2015-01-01

    Several parameters for improving volatile metabolite analysis using headspace gas chromatography-mass spectrometry (GC-MS) analysis of volatile metabolites were evaluated in the framework of identification of mastitis-causing pathogens. Previous research showed that the results of such volatile

  3. A Two-Stage Meta-Analysis Identifies Several New Loci for Parkinson's Disease

    NARCIS (Netherlands)

    Plagnol, Vincent; Nalls, Michael A.; Bras, Jose M.; Hernandez, Dena G.; Sharma, Manu; Sheerin, Una-Marie; Saad, Mohamad; Simon-Sanchez, Javier; Schulte, Claudia; Lesage, Suzanne; Sveinbjornsdottir, Sigurlaug; Amouyel, Philippe; Arepalli, Sampath; Band, Gavin; Barker, Roger A.; Bellinguez, Celine; Ben-Shlomo, Yoav; Berendse, Henk W.; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M. A.; Biffi, Alessandro; Bloem, Bas; Bochdanovits, Zoltan; Bonin, Michael; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chen, Honglei; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Cooper, J. Mark; Corvol, Jean Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean-Francois; Deloukas, Panos; Deuschl, Guenther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Durif, Frank; Duerr, Alexandra; Edkins, Sarah; Evans, Jonathan R.; Foltynie, Thomas; Freeman, Colin; Gao, Jianjun; Gardner, Michelle; Gibbs, J. Raphael; Goate, Alison; Gray, Emma; Guerreiro, Rita; Gustafsson, Omar; Harris, Clare; Hellenthal, Garrett; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holton, Janice; Hu, Michele; Huang, Xuemei; Huber, Heiko; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; Jonsson, Palmi V.; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw; Morrison, Karen E.; Mudanohwo, Ese; O'Sullivan, Sean S.; Pearson, Justin; Pearson, Richard; Perlmutter, Joel S.; Petursson, Hjoervar; Pirinen, Matti; Pollak, Pierre; Post, Bart; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Shaw, Karen; Shoulson, Ira; Sidransky, Ellen; de Silva, Rohan; Smith, Colin; Spencer, Chris C. A.; Stefansson, Hreinn; Steinberg, Stacy; Stockton, Joanna D.; Strange, Amy; Su, Zhan; Talbot, Kevin; Tanner, Carlie M.; Tashakkori-Ghanbaria, Avazeh; Tison, Francois; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, Andre G.; Vandrovcova, Jana; Velseboer, Daan; Vidailhet, Marie; Vukcevic, Damjan; Walker, Robert; van de Warrenburg, Bart; Weale, Michael E.; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Stefansson, Kari; Martinez, Maria; Donnelly, Peter; Singleton, Andrew B.; Hardy, John; Heutink, Peter; Brice, Alexis; Gasser, Thomas; Wood, Nicholas W.

    2011-01-01

    A previous genome-wide association (GWA) meta-analysis of 12,386 PD cases and 21,026 controls conducted by the International Parkinson's Disease Genomics Consortium (IPDGC) discovered or confirmed 11 Parkinson's disease (PD) loci. This first analysis of the two-stage IPDGC study focused on the set

  4. Blood Meal Analysis to Identify Reservoir Hosts for Amblyomma americanum Ticks

    Science.gov (United States)

    Goessling, Lisa S.; Storch, Gregory A.; Thach, Robert E.

    2010-01-01

    Efforts to identify wildlife reservoirs for tick-borne pathogens are frequently limited by poor understanding of tick–host interactions and potentially transient infectivity of hosts under natural conditions. To identify reservoir hosts for lone star tick (Amblyomma americanum)–associated pathogens, we used a novel technology. In field-collected ticks, we used PCR to amplify a portion of the 18S rRNA gene in remnant blood meal DNA. Reverse line blot hybridization with host-specific probes was then used to subsequently detect and identify amplified DNA. Although several other taxa of wildlife hosts contribute to tick infection rates, our results confirm that the white-tailed deer (Odocoileus virginianus) is a reservoir host for several A. americanum–associated pathogens. Identification of host blood meal frequency and reservoir competence can help in determining human infection rates caused by these pathogens. PMID:20202418

  5. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis

    Science.gov (United States)

    Beecham, Ashley H; Patsopoulos, Nikolaos A; Xifara, Dionysia K; Davis, Mary F; Kemppinen, Anu; Cotsapas, Chris; Shahi, Tejas S; Spencer, Chris; Booth, David; Goris, An; Oturai, Annette; Saarela, Janna; Fontaine, Bertrand; Hemmer, Bernhard; Martin, Claes; Zipp, Frauke; D’alfonso, Sandra; Martinelli-Boneschi, Filippo; Taylor, Bruce; Harbo, Hanne F; Kockum, Ingrid; Hillert, Jan; Olsson, Tomas; Ban, Maria; Oksenberg, Jorge R; Hintzen, Rogier; Barcellos, Lisa F; Agliardi, Cristina; Alfredsson, Lars; Alizadeh, Mehdi; Anderson, Carl; Andrews, Robert; Søndergaard, Helle Bach; Baker, Amie; Band, Gavin; Baranzini, Sergio E; Barizzone, Nadia; Barrett, Jeffrey; Bellenguez, Céline; Bergamaschi, Laura; Bernardinelli, Luisa; Berthele, Achim; Biberacher, Viola; Binder, Thomas M C; Blackburn, Hannah; Bomfim, Izaura L; Brambilla, Paola; Broadley, Simon; Brochet, Bruno; Brundin, Lou; Buck, Dorothea; Butzkueven, Helmut; Caillier, Stacy J; Camu, William; Carpentier, Wassila; Cavalla, Paola; Celius, Elisabeth G; Coman, Irène; Comi, Giancarlo; Corrado, Lucia; Cosemans, Leentje; Cournu-Rebeix, Isabelle; Cree, Bruce A C; Cusi, Daniele; Damotte, Vincent; Defer, Gilles; Delgado, Silvia R; Deloukas, Panos; di Sapio, Alessia; Dilthey, Alexander T; Donnelly, Peter; Dubois, Bénédicte; Duddy, Martin; Edkins, Sarah; Elovaara, Irina; Esposito, Federica; Evangelou, Nikos; Fiddes, Barnaby; Field, Judith; Franke, Andre; Freeman, Colin; Frohlich, Irene Y; Galimberti, Daniela; Gieger, Christian; Gourraud, Pierre-Antoine; Graetz, Christiane; Graham, Andrew; Grummel, Verena; Guaschino, Clara; Hadjixenofontos, Athena; Hakonarson, Hakon; Halfpenny, Christopher; Hall, Gillian; Hall, Per; Hamsten, Anders; Harley, James; Harrower, Timothy; Hawkins, Clive; Hellenthal, Garrett; Hillier, Charles; Hobart, Jeremy; Hoshi, Muni; Hunt, Sarah E; Jagodic, Maja; Jelčić, Ilijas; Jochim, Angela; Kendall, Brian; Kermode, Allan; Kilpatrick, Trevor; Koivisto, Keijo; Konidari, Ioanna; Korn, Thomas; Kronsbein, Helena; Langford, Cordelia; Larsson, Malin; Lathrop, Mark; Lebrun-Frenay, Christine; Lechner-Scott, Jeannette; Lee, Michelle H; Leone, Maurizio A; Leppä, Virpi; Liberatore, Giuseppe; Lie, Benedicte A; Lill, Christina M; Lindén, Magdalena; Link, Jenny; Luessi, Felix; Lycke, Jan; Macciardi, Fabio; Männistö, Satu; Manrique, Clara P; Martin, Roland; Martinelli, Vittorio; Mason, Deborah; Mazibrada, Gordon; McCabe, Cristin; Mero, Inger-Lise; Mescheriakova, Julia; Moutsianas, Loukas; Myhr, Kjell-Morten; Nagels, Guy; Nicholas, Richard; Nilsson, Petra; Piehl, Fredrik; Pirinen, Matti; Price, Siân E; Quach, Hong; Reunanen, Mauri; Robberecht, Wim; Robertson, Neil P; Rodegher, Mariaemma; Rog, David; Salvetti, Marco; Schnetz-Boutaud, Nathalie C; Sellebjerg, Finn; Selter, Rebecca C; Schaefer, Catherine; Shaunak, Sandip; Shen, Ling; Shields, Simon; Siffrin, Volker; Slee, Mark; Sorensen, Per Soelberg; Sorosina, Melissa; Sospedra, Mireia; Spurkland, Anne; Strange, Amy; Sundqvist, Emilie; Thijs, Vincent; Thorpe, John; Ticca, Anna; Tienari, Pentti; van Duijn, Cornelia; Visser, Elizabeth M; Vucic, Steve; Westerlind, Helga; Wiley, James S; Wilkins, Alastair; Wilson, James F; Winkelmann, Juliane; Zajicek, John; Zindler, Eva; Haines, Jonathan L; Pericak-Vance, Margaret A; Ivinson, Adrian J; Stewart, Graeme; Hafler, David; Hauser, Stephen L; Compston, Alastair; McVean, Gil; De Jager, Philip; Sawcer, Stephen; McCauley, Jacob L

    2013-01-01

    Using the ImmunoChip custom genotyping array, we analysed 14,498 multiple sclerosis subjects and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (p-value multiple sclerosis subjects and 26,703 healthy controls. In these 80,094 individuals of European ancestry we identified 48 new susceptibility variants (p-value multiple sclerosis risk variants in 103 discrete loci outside of the Major Histocompatibility Complex. With high resolution Bayesian fine-mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalogue of multiple sclerosis risk variants and illustrates the value of fine-mapping in the resolution of GWAS signals. PMID:24076602

  6. Differentially expressed genes in pancreatic ductal adenocarcinomas identified through serial analysis of gene expression

    DEFF Research Database (Denmark)

    Hustinx, Steven R; Cao, Dengfeng; Maitra, Anirban

    2004-01-01

    generated from six pancreatic cancers were compared to SAGE libraries generated from 11 non-neoplastic tissues. Compared to normal tissue libraries, we identified 453 SAGE tags as differentially expressed in pancreatic cancer, including 395 that mapped to known genes and 58 "uncharacterized" tags....... Of the 395 SAGE tags assigned to known genes, 223 were overexpressed in pancreatic cancer, and 172 were underexpressed. In order to map the 58 uncharacterized differentially expressed SAGE tags to genes, we used a newly developed resource called TAGmapper (http://tagmapper.ibioinformatics.org), to identify...

  7. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

    NARCIS (Netherlands)

    Pharoah, P.D.; Tsai, Y.Y.; Ramus, S.J.; Phelan, C.M.; Goode, E.L.; Lawrenson, K.; Buckley, M.; Fridley, B.L.; Tyrer, J.P.; Shen, H.; Weber, R.; Karevan, R.; Larson, M.C.; Song, H.; Tessier, D.C.; Bacot, F.; Vincent, D.; Cunningham, J.M.; Dennis, J.; Dicks, E.; Aben, K.K.H.; Anton-Culver, H.; Antonenkova, N.; Armasu, S.M.; Baglietto, L.; Bandera, E.V.; Beckmann, M.W.; Birrer, M.J.; Bloom, G.; Bogdanova, N.; Brenton, J.D.; Brinton, L.A.; Brooks-Wilson, A.; Brown, R.; Butzow, R.; Campbell, I.; Carney, M.E.; Carvalho, R.S.; Chang-Claude, J.; Chen, Y.A.; Chen, Z.; Chow, W.H.; Cicek, M.S.; Coetzee, G.; Cook, L.S.; Cramer, D.W; Cybulski, C.; Dansonka-Mieszkowska, A.; Despierre, E.; Doherty, J.A.; Dork, T.; Bois, A. du; Durst, M.; Eccles, D.; Edwards, R.; Ekici, A.B.; Fasching, P.A.; Fenstermacher, D.; Flanagan, J.; Gao, Y.T.; Garcia-Closas, M.; Gentry-Maharaj, A.; Giles, G.; Gjyshi, A.; Gore, M.; Gronwald, J.; Guo, Q.; Halle, M.K.; Harter, P.; Hein, A.; Heitz, F.; Hillemanns, P.; Hoatlin, M.; Hogdall, E.; Hogdall, C.K.; Hosono, S.; Jakubowska, A.; Jensen, A.; Kalli, K.R.; Karlan, B.Y.; Kelemen, L.E.; Kiemeney, L.A.L.M.; Kjaer, S.K.; Konecny, G.E.; Krakstad, C.; Kupryjanczyk, J.; Lambrechts, D.; Lambrechts, S.; Le, N.D.; Lee, N.; Lee, J. van der; Leminen, A.; Lim, B.K.; Lissowska, J.; Lubinski, J.; Lundvall, L.; Lurie, G.; Massuger, L.F.A.G.; Altena, A.M. van

    2013-01-01

    Genome-wide association studies (GWAS) have identified four susceptibility loci for epithelial ovarian cancer (EOC), with another two suggestive loci reaching near genome-wide significance. We pooled data from a GWAS conducted in North America with another GWAS from the UK. We selected the top

  8. Use of amplified fragment length polymorphism analysis to identify medically important Candida spp., including C. dubliniensis.

    NARCIS (Netherlands)

    Borst, A; Theelen, B; Reinders, E; Boekhout, T; Fluit, AC; Savelkoul, P.H.M.

    2003-01-01

    Non-Candida albicans Candida species are increasingly being isolated. These species show differences in levels of resistance to antimycotic agents and mortality. Therefore, it is important to be able to correctly identify the causative organism to the species level. Identification of C. dubliniensis

  9. Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

    NARCIS (Netherlands)

    Barban, N.; Jansen, R.; de Vlaming, Ronald; Vaez, A.; Mandemakers, J.J.; Tropf, F.C.; Shen, X.; Wilson, J.F.; Chasman, D.I.; Nolte, I.M.; Mbarek, H.; Boomsma, D.I.; de Geus, E.J.C.; Penninx, B.W.J.H.; Willemsen, G.; Zondervan, K.T.; Stefansson, K.; Krueger, R.F.; Lee, J.J.; Benjamin, D.J.; Cesarini, D.; Koellinger, P.D.; den Hoed, M.A.H.; Snieder, H.; Mills, M.C.

    2016-01-01

    The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the

  10. Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci

    NARCIS (Netherlands)

    Asselbergs, Folkert W.; Guo, Yiran; van Iperen, Erik P. A.; Sivapalaratnam, Suthesh; Tragante, Vinicius; Lanktree, Matthew B.; Lange, Leslie A.; Almoguera, Berta; Appelman, Yolande E.; Barnard, John; Baumert, Jens; Beitelshees, Amber L.; Bhangale, Tushar R.; Chen, Yii-Der Ida; Gaunt, Tom R.; Gong, Yan; Hopewell, Jemma C.; Johnson, Toby; Kleber, Marcus E.; Langaee, Taimour Y.; Li, Mingyao; Li, Yun R.; Liu, Kiang; McDonough, Caitrin W.; Meijs, Matthijs F. L.; Middelberg, Rita P. S.; Musunuru, Kiran; Nelson, Christopher P.; O'Connell, Jeffery R.; Padmanabhan, Sandosh; Pankow, James S.; Pankratz, Nathan; Rafelt, Suzanne; Rajagopalan, Ramakrishnan; Romaine, Simon P. R.; Schork, Nicholas J.; Shaffer, Jonathan; Shen, Haiqing; Smith, Erin N.; Tischfield, Sam E.; van der Most, Peter J.; van Vliet-Ostaptchouk, Jana V.; Verweij, Niek; Volcik, Kelly A.; Zhang, Li; Bailey, Kent R.; Bailey, Kristian M.; Bauer, Florianne; Boer, Jolanda M. A.; Braund, Peter S.; Burt, Amber; Burton, Paul R.; Buxbaum, Sarah G.; Chen, Wei; Cooper-DeHoff, Rhonda M.; Cupples, L. Adrienne; Dejong, Jonas S.; Delles, Christian; Duggan, David; Fornage, Myriam; Furlong, Clement E.; Glazer, Nicole; Gums, John G.; Hastie, Claire; Holmes, Michael V.; Illig, Thomas; Kirkland, Susan A.; Kivimaki, Mika; Klein, Ronald; Klein, Barbara E.; Kooperberg, Charles; Kottke-Marchant, Kandice; Kumari, Meena; LaCroix, Andrea Z.; Mallela, Laya; Murugesan, Gurunathan; Ordovas, Jose; Ouwehand, Willem H.; Post, Wendy S.; Saxena, Richa; Scharnagl, Hubert; Schreiner, Pamela J.; Shah, Tina; Shields, Denis C.; Shimbo, Daichi; Srinivasan, Sathanur R.; Stolk, Ronald P.; Swerdlow, Daniel I.; Taylor, Herman A.; Topol, Eric J.; Toskala, Elina; van Pelt, Joost L.; van Setten, Jessica; Yusuf, Salim; Whittaker, John C.; Zwinderman, A. H.; Anand, Sonia S.; Balmforth, Anthony J.; Berenson, Gerald S.; Bezzina, Connie R.; Boehm, Bernhard O.; Boerwinkle, Eric; Casas, Juan P.; Caulfield, Mark J.; Clarke, Robert; Connell, John M.; Cruickshanks, Karen J.; Davidson, Karina W.; Day, Ian N. M.; de Bakker, Paul I. W.; Doevendans, Pieter A.; Dominiczak, Anna F.; Hall, Alistair S.; Hartman, Catharina A.; Hengstenberg, Christian; Hillege, Hans L.; Hofker, Marten H.; Humphries, Steve E.; Jarvik, Gail P.; Johnson, Julie A.; Kaess, Bernhard M.; Kathiresan, Sekar; Koenig, Wolfgang; Lawlor, Debbie A.; März, Winfried; Melander, Olle; Mitchell, Braxton D.; Montgomery, Grant W.; Munroe, Patricia B.; Murray, Sarah S.; Newhouse, Stephen J.; Onland-Moret, N. Charlotte; Poulter, Neil; Psaty, Bruce; Redline, Susan; Rich, Stephen S.; Rotter, Jerome I.; Schunkert, Heribert; Sever, Peter; Shuldiner, Alan R.; Silverstein, Roy L.; Stanton, Alice; Thorand, Barbara; Trip, Mieke D.; Tsai, Michael Y.; van der Harst, Pim; van der Schoot, Ellen; van der Schouw, Yvonne T.; Verschuren, W. M. Monique; Watkins, Hugh; Wilde, Arthur A. M.; Wolffenbuttel, Bruce H. R.; Whitfield, John B.; Hovingh, G. Kees; Ballantyne, Christie M.; Wijmenga, Cisca; Reilly, Muredach P.; Martin, Nicholas G.; Wilson, James G.; Rader, Daniel J.; Samani, Nilesh J.; Reiner, Alex P.; Hegele, Robert A.; Kastelein, John J. P.; Hingorani, Aroon D.; Talmud, Philippa J.; Hakonarson, Hakon; Elbers, Clara C.; Keating, Brendan J.; Drenos, Fotios; de Boer, Rudolf; Hillege, Hans; van der Klauw, Melanie; Navis, Gerjan; Ormel, Hans; Postma, Dirkje; Rosmalen, Judith; Slaets, Joris; Stolk, Ronald; Wolffenbuttel, Bruce; Alizadeh, Behrooz; Boezen, Marike; Bruinenberg, Marcel; Festen, Noortje; Franke, Lude; Snieder, Harold

    2012-01-01

    Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total

  11. 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function

    NARCIS (Netherlands)

    Gorski, Mathias; Van der Most, Peter J.; Teumer, Alexander; Chu, Audrey Y.; Li, Man; Mijatovic, Vladan; Nolte, Ilja M.; Cocca, Massimiliano; Taliun, Daniel; Gomez, Felicia; Li, Yong; Tayo, Bamidele; Tin, Adrienne; Feitosa, Mary F.; Aspelund, Thor; Attia, John; Biffar, Reiner; Bochud, Murielle; Boerwinkle, Eric; Borecki, Ingrid; Bottinger, Erwin P.; Chen, Ming-Huei; Chouraki, Vincent; Ciullo, Marina; Coresh, Josef; Cornelis, Marilyn C.; Curhan, Gary C.; d'Adamo, Adamo Pio; Dehghan, Abbas; Dengler, Laura; Ding, Jingzhong; Eiriksdottir, Gudny; Endlich, Karlhans; Enroth, Stefan; Esko, Tonu; Franco, Oscar H.; Gasparini, Paolo; Gieger, Christian; Girotto, Giorgia; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Hancock, Stephen J.; Harris, Tamara B.; Helmer, Catherine; Hoellerer, Simon; Hofer, Edith; Hofman, Albert; Holliday, Elizabeth G.; Homuth, Georg; Hu, Frank B.; Huth, Cornelia; Hutri-Kahonen, Nina; Hwang, Shih-Jen; Imboden, Medea; Johansson, Asa; Kahonen, Mika; Koenig, Wolfgang; Kraemer, Holly; Kramer, Bernhard K.; Kumar, Ashish; Kutalik, Zoltan; Lambert, Jean-Charles; Launer, Lenore J.; Lehtimaki, Terho; de Borst, Martin; Navis, Gerjan; Swertz, Morris; Liu, Yongmei; Lohman, Kurt; Loos, Ruth J. F.; Lu, Yingchang; Lyytikainen, Leo-Pekka; McEvoy, Mark A.; Meisinger, Christa; Meitinger, Thomas; Metspalu, Andres; Metzger, Marie; Mihailov, Evelin; Mitchell, Paul; Nauck, Matthias; Oldehinkel, Albertine J.; Olden, Matthias; Penninx, Brenda W. J. H.; Pistis, Giorgio; Pramstaller, Peter P.; Probst-Hensch, Nicole; Raitakari, Olli T.; Rettig, Rainer; Ridker, Paul M.; Rivadeneira, Fernando; Robino, Antonietta; Rosas, Sylvia E.; Ruderfer, Douglas; Ruggiero, Daniela; Saba, Yasaman; Sala, Cinzia; Schmidt, Helena; Schmidt, Reinhold; Scott, Rodney J.; Sedaghat, Sanaz; Smith, Albert V.; Sorice, Rossella; Stengel, Benedicte; Stracke, Sylvia; Strauch, Konstantin; Toniolo, Daniela; Uitterlinden, Andre G.; Ulivi, Sheila; Viikari, Jorma S.; Voelker, Uwe; Vollenweider, Peter; Voelzke, Henry; Vuckovic, Dragana; Waldenberger, Melanie; Wang, Jie Jin; Yang, Qiong; Chasman, Daniel I.; Tromp, Gerard; Snieder, Harold; Heid, Iris M.; Fox, Caroline S.; Koettgen, Anna; Pattaro, Cristian; Boeger, Carsten A.; Fuchsberger, Christian

    2017-01-01

    HapMap imputed genome-wide association studies (GWAS) have revealed > 50 loci at which common variants with minor allele frequency > 5% are associated with kidney function. GWAS using more complete reference sets for imputation, such as those from The 1000 Genomes project, promise to identify novel

  12. Identifying classes of persons with mild intellectual disability or borderline intellectual functioning : A latent class analysis

    NARCIS (Netherlands)

    Nouwens, P.J.G.; Lucas, R.; Smulders, N.B.M.; Embregts, P.J.C.M.; van Nieuwenhuizen, Ch.

    2017-01-01

    Background Persons with mild intellectual disability or borderline intellectual functioning are often studied as a single group with similar characteristics. However, there are indications that differences exist within this population. Therefore, the aim of this study was to identify classes of

  13. Genome-wide association analysis identifies three new breast cancer susceptibility loci

    DEFF Research Database (Denmark)

    Ghoussaini, Maya; Fletcher, Olivia; Michailidou, Kyriaki

    2012-01-01

    Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ∼8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ...

  14. Genome-based exome sequencing analysis identifies GYG1, DIS3L ...

    Indian Academy of Sciences (India)

    JI-YOUNG LEE

    2017-11-28

    Nov 28, 2017 ... Abstract. Myocardial infarction (MI) is a complex disease caused by combination of genetic and environmental factors. Although genome-wide association studies (GWAS) identified more than 46 risk loci which are associated with coronary artery disease and MI, most of the genetic variability in MI still ...

  15. Using Critical Thinking to Identify Bias in the News Media: The Art of Critical Analysis.

    Science.gov (United States)

    Paul, Richard W.; Adamson, Kenneth R.

    1990-01-01

    Urges social studies teachers to help students understand and identify sociocentric, national bias in the news media. Illustrates how the media fosters "us versus them" thinking and how word choice often reflects bias. Outlines activities to help students recognize bias. Provides weak and strong examples of students' analyses of bias in news…

  16. Genome-wide analysis identifies 12 loci influencing human reproductive behavior

    NARCIS (Netherlands)

    Barban, Nicola; Jansen, Rick; de Vlaming, Ronald; Vaez, Ahmad; Mandemakers, Jornt J; Tropf, Felix C; Shen, Xia; Wilson, James F; Chasman, Daniel I; Nolte, Ilja M; Tragante, Vinicius; van der Laan, Sander W; Perry, John R B; Kong, Augustine; Ahluwalia, Tarunveer S; Albrecht, Eva; Yerges-Armstrong, Laura; Atzmon, Gil; Auro, Kirsi; Ayers, Kristin; Bakshi, Andrew; Ben-Avraham, Danny; Berger, Klaus; Bergman, Aviv; Bertram, Lars; Bielak, Lawrence F; Bjornsdottir, Gyda; Bonder, Marc Jan; Broer, Linda; Bui, Minh; Barbieri, Caterina; Cavadino, Alana; Chavarro, Jorge E; Turman, Constance; Concas, Maria Pina; Cordell, Heather J; Davies, Gail; Eibich, Peter; Eriksson, Nicholas; Esko, Tõnu; Eriksson, Joel; Falahi, Fahimeh; Felix, Janine F; Fontana, Mark Alan; Franke, Lude; Gandin, Ilaria; Gaskins, Audrey J; Gieger, Christian; Gunderson, Erica P; Guo, Xiuqing; Hayward, Caroline; He, Chunyan; Hofer, Edith; Huang, Hongyan; Joshi, Peter K; Kanoni, Stavroula; Karlsson, Robert; Kiechl, Stefan; Kifley, Annette; Kluttig, Alexander; Kraft, Peter; Lagou, Vasiliki; Lecoeur, Cecile; Lahti, Jari; Li-Gao, Ruifang; Lind, Penelope A; Liu, Tian; Makalic, Enes; Mamasoula, Crysovalanto; Matteson, Lindsay; Mbarek, Hamdi; McArdle, Patrick F; McMahon, George; Meddens, S Fleur W; Mihailov, Evelin; Miller, Mike; Missmer, Stacey A; Monnereau, Claire; van der Most, Peter J; Myhre, Ronny; Nalls, Mike A; Nutile, Teresa; Kalafati, Ioanna Panagiota; Porcu, Eleonora; Prokopenko, Inga; Rajan, Kumar B; Rich-Edwards, Janet; Rietveld, Cornelius A; Robino, Antonietta; Rose, Lynda M; Rueedi, Rico; Ryan, Kathleen A; Saba, Yasaman; Schmidt, Daniel; Smith, Jennifer A; Stolk, Lisette; Streeten, Elizabeth; Tönjes, Anke; Thorleifsson, Gudmar; Ulivi, Sheila; Wedenoja, Juho; Wellmann, Juergen; Willeit, Peter; Yao, Jie; Yengo, Loic; Zhao, Jing Hua; Zhao, Wei; Zhernakova, Daria V; Amin, Najaf; Andrews, Howard; Balkau, Beverley; Barzilai, Nir; Bergmann, Sven; Biino, Ginevra; Bisgaard, Hans; Bønnelykke, Klaus; Boomsma, Dorret I; Buring, Julie E; Campbell, Harry; Cappellani, Stefania; Ciullo, Marina; Cox, Simon R; Cucca, Francesco; Toniolo, Daniela; Davey-Smith, George; Deary, Ian J; Dedoussis, George; Deloukas, Panos; van Duijn, Cornelia M; de Geus, Eco J C; Eriksson, Johan G; Evans, Denis A; Faul, Jessica D; Sala, Cinzia Felicita; Froguel, Philippe; Gasparini, Paolo; Girotto, Giorgia; Grabe, Hans-Jörgen; Greiser, Karin Halina; Groenen, Patrick J F; de Haan, Hugoline G; Haerting, Johannes; Harris, Tamara B; Heath, Andrew C; Heikkilä, Kauko; Hofman, Albert; Homuth, Georg; Holliday, Elizabeth G; Hopper, John; Hyppönen, Elina; Jacobsson, Bo; Jaddoe, Vincent W V; Johannesson, Magnus; Jugessur, Astanand; Kähönen, Mika; Kajantie, Eero; Kardia, Sharon L R; Keavney, Bernard; Kolcic, Ivana; Koponen, Päivikki; Kovacs, Peter; Kronenberg, Florian; Kutalik, Zoltan; La Bianca, Martina; Lachance, Genevieve; Iacono, William G; Lai, Sandra; Lehtimäki, Terho; Liewald, David C; Lindgren, Cecilia M; Liu, Yongmei; Luben, Robert; Lucht, Michael; Luoto, Riitta; Magnus, Per; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; McQuillan, Ruth; Medland, Sarah E; Meisinger, Christa; Mellström, Dan; Metspalu, Andres; Traglia, Michela; Milani, Lili; Mitchell, Paul; Montgomery, Grant W; Mook-Kanamori, Dennis; de Mutsert, Renée; Nohr, Ellen A; Ohlsson, Claes; Olsen, Jørn; Ong, Ken K; Paternoster, Lavinia; Pattie, Alison; Penninx, Brenda W J H; Perola, Markus; Peyser, Patricia A; Pirastu, Mario; Polasek, Ozren; Power, Chris; Kaprio, Jaakko; Raffel, Leslie J; Räikkönen, Katri; Raitakari, Olli; Ridker, Paul M; Ring, Susan M; Roll, Kathryn; Rudan, Igor; Ruggiero, Daniela; Rujescu, Dan; Salomaa, Veikko; Schlessinger, David; Schmidt, Helena; Schmidt, Reinhold; Schupf, Nicole; Smit, Johannes; Sorice, Rossella; Spector, Tim D; Starr, John M; Stöckl, Doris; Strauch, Konstantin; Stumvoll, Michael; Swertz, Morris A; Thorsteinsdottir, Unnur; Thurik, A Roy; Timpson, Nicholas J; Tung, Joyce Y; Uitterlinden, André G; Vaccargiu, Simona; Viikari, Jorma; Vitart, Veronique; Völzke, Henry; Vollenweider, Peter; Vuckovic, Dragana; Waage, Johannes; Wagner, Gert G; Wang, Jie Jin; Wareham, Nicholas J; Weir, David R; Willemsen, Gonneke; Willeit, Johann; Wright, Alan F; Zondervan, Krina T; Stefansson, Kari; Krueger, Robert F; Lee, James J; Benjamin, Daniel J; Cesarini, David; Koellinger, Philipp D; den Hoed, Marcel; Snieder, Harold; Mills, Melinda C

    2016-01-01

    The genetic architecture of human reproductive behavior age at first birth (AFB) and number of children ever born (NEB) has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the

  17. Genome-wide analysis identifies 12 loci influencing human reproductive behavior

    NARCIS (Netherlands)

    Barban, Nicola; Jansen, Rick; De Vlaming, Ronald; Vaez, Ahmad; Mandemakers, Jornt J.; Tropf, Felix C.; Shen, Xia; Wilson, James F.; Chasman, Daniel I.; Nolte, Ilja M.; Tragante, Vinicius; Van Der Laan, Sander W.; Perry, John R B; Kong, Augustine; Ahluwalia, Tarunveer S.; Albrecht, Eva; Yerges-Armstrong, Laura; Atzmon, Gil; Auro, Kirsi; Ayers, Kristin; Bakshi, Andrew; Ben-Avraham, Danny; Berger, Klaus; Bergman, Aviv; Bertram, Lars; Bielak, Lawrence F.; Bjornsdottir, Gyda; Bonder, Marc Jan; Broer, Linda; Bui, Minh; Barbieri, Caterina; Cavadino, Alana; Chavarro, Jorge E.; Turman, Constance; Concas, Maria Pina; Cordell, Heather J.; Davies, Gail; Eibich, Peter; Eriksson, Nicholas; Esko, Tõnu; Eriksson, Joel; Falahi, Fahimeh; Felix, Janine F.; Fontana, Mark Alan; Franke, Lude; Gandin, Ilaria; Gaskins, Audrey J.; Gieger, Christian; Gunderson, Erica P.; Guo, Xiuqing; Hayward, Caroline; He, Chunyan; Hofer, Edith; Huang, Hongyan; Joshi, Peter K.; Kanoni, Stavroula; Karlsson, Robert; Kiechl, Stefan; Kifley, Annette; Kluttig, Alexander; Kraft, Peter; Lagou, Vasiliki; Lecoeur, Cecile; Lahti, Jari; Li-Gao, Ruifang; Lind, Penelope A.; Liu, Tian; Makalic, Enes; Mamasoula, Crysovalanto; Matteson, Lindsay; Mbarek, Hamdi; McArdle, Patrick F.; McMahon, George; Meddens, S. Fleur W; Mihailov, Evelin; Miller, Mike; Missmer, Stacey A.; Monnereau, Claire; Van Der Most, Peter J.; Myhre, Ronny; Nalls, Mike A.; Nutile, Teresa; Kalafati, Ioanna Panagiota; Porcu, Eleonora; Prokopenko, Inga; Rajan, Kumar B.; Rich-Edwards, Janet; Rietveld, Cornelius A.; Robino, Antonietta; Rose, Lynda M.; Rueedi, Rico; Ryan, Kathleen A.; Saba, Yasaman; Schmidt, Daniel; Smith, Jennifer A.; Stolk, Lisette; Streeten, Elizabeth; Tönjes, Anke; Thorleifsson, Gudmar; Ulivi, Sheila; Wedenoja, Juho; Wellmann, Juergen; Willeit, Peter; Yao, Jie; Yengo, Loic; Zhao, Jing Hua; Zhao, Wei; Zhernakova, Daria V.; Amin, Najaf; Andrews, Howard; Balkau, Beverley; Barzilai, Nir; Bergmann, Sven; Biino, Ginevra; Bisgaard, Hans; Bønnelykke, Klaus; Boomsma, Dorret I.; Buring, Julie E.; Campbell, Harry; Cappellani, Stefania; Ciullo, Marina; Cox, Simon R.; Cucca, Francesco; Toniolo, Daniela; Davey-Smith, George; Deary, Ian J.; Dedoussis, George; Deloukas, Panos; Van Duijn, Cornelia M.; De Geus, Eco J C; Eriksson, Johan G.; Evans, Denis A.; Faul, Jessica D.; Sala, Cinzia Felicita; Froguel, Philippe; Gasparini, Paolo; Girotto, Giorgia; Grabe, Hans Jörgen; Greiser, Karin Halina; Groenen, Patrick J F; De Haan, Hugoline G.; Haerting, Johannes; Harris, Tamara B.; Heath, Andrew C.; Heikkilä, Kauko; Hofman, Albert; Homuth, Georg; Holliday, Elizabeth G.; Hopper, John; Hyppönen, Elina; Jacobsson, Bo; Jaddoe, Vincent W V; Johannesson, Magnus; Jugessur, Astanand; Kähönen, Mika; Kajantie, Eero; Kardia, Sharon L R; Keavney, Bernard; Kolcic, Ivana; Koponen, Päivikki; Kovacs, Peter; Kronenberg, Florian; Kutalik, Zoltan; La Bianca, Martina; Lachance, Genevieve; Iacono, William G.; Lai, Sandra; Lehtimäki, Terho; Liewald, David C.; Lindgren, Cecilia M.; Liu, Yongmei; Luben, Robert; Lucht, Michael; Luoto, Riitta; Magnus, Per; Magnusson, Patrikke; Martin, Nicholas G.; McGue, Matt; McQuillan, Ruth; Medland, Sarah E.; Meisinger, Christa; Mellström, Dan; Metspalu, Andres; Traglia, Michela; Milani, Lili; Mitchell, Paul; Montgomery, Grant W.; Mook-Kanamori, Dennis; De Mutsert, Renée; Nohr, Ellen A.; Ohlsson, Claes; Olsen, Jørn; Ong, Ken K.; Paternoster, Lavinia; Pattie, Alison; Penninx, Brenda W J H; Perola, Markus; Peyser, Patricia A.; Pirastu, Mario; Polasek, Ozren; Power, Chris; Kaprio, Jaakko; Raffel, Leslie J.; Räikkönen, Katri; Raitakari, Olli; Ridker, Paul M.; Ring, Susan M.; Roll, Kathryn; Rudan, Igor; Ruggiero, Daniela; Rujescu, Dan; Salomaa, Veikko; Schlessinger, David; Schmidt, Helena; Schmidt, Reinhold; Schupf, Nicole; Smit, Johannes; Sorice, Rossella; Spector, Tim D.; Starr, John M.; Stöckl, Doris; Strauch, Konstantin; Stumvoll, Michael; Swertz, Morris A.; Thorsteinsdottir, Unnur; Roy Thurik, A.; Timpson, Nicholas J.; Tung, Joyce Y.; Uitterlinden, André G.; Vaccargiu, Simona; Viikari, Jorma; Vitart, Veronique; Völzke, Henry; Vollenweider, Peter; Vuckovic, Dragana; Waage, Johannes; Wagner, Gert G.; Wang, Jie Jin; Wareham, Nicholas J.; Weir, David R.; Willemsen, Gonneke; Willeit, Johann; Wright, Alan F.; Zondervan, Krina T.; Stefansson, Kari; Krueger, Robert F.; Lee, James J.; Benjamin, Daniel J.; Cesarini, David; Koellinger, Philipp D.; Den Hoed, Marcel; Snieder, Harold; Mills, Melinda C.

    2016-01-01

    The genetic architecture of human reproductive behavior - age at first birth (AFB) and number of children ever born (NEB) - has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the

  18. Genome-wide analysis identifies 12 loci influencing human reproductive behavior

    NARCIS (Netherlands)

    Barban, Nicola; Jansen, Rick; Vlaming, de Ronald; Vaez, Ahmad; Mandemakers, Jornt J.; Tropf, Felix C.; Shen, Xia; Wilson, James F.; Chasman, Daniel I.; Nolte, Ilja M.; Tragante, Vinicius; Laan, van der Sander W.; Perry, John R.B.; Kong, Augustine; Ahluwalia, Tarunveer S.; Albrecht, Eva; Yerges-Armstrong, Laura; Atzmon, Gil; Auro, Kirsi; Ayers, Kristin; Bakshi, Andrew; Ben-Avraham, Danny; Berger, Klaus; Bergman, Aviv; Bertram, Lars; Bielak, Lawrence F.; Bjornsdottir, Gyda; Bonder, Marc Jan; Broer, Linda; Bui, Minh; Barbieri, Caterina; Cavadino, Alana; Chavarro, Jorge E.; Turman, Constance; Concas, Maria Pina; Cordell, Heather J.; Davies, Gail; Eibich, Peter; Eriksson, Nicholas; Esko, Tõnu; Eriksson, Joel; Falahi, Fahimeh; Felix, Janine F.; Fontana, Mark Alan; Franke, Lude; Gandin, Ilaria; Gaskins, Audrey J.; Gieger, Christian; Gunderson, Erica P.; Guo, Xiuqing; Hayward, Caroline; He, Chunyan; Hofer, Edith; Huang, Hongyan; Joshi, Peter K.; Kanoni, Stavroula; Karlsson, Robert; Kiechl, Stefan; Kifley, Annette; Kluttig, Alexander; Kraft, Peter; Lagou, Vasiliki; Lecoeur, Cecile; Lahti, Jari; Li-Gao, Ruifang; Lind, Penelope A.; Liu, Tian; Makalic, Enes; Mamasoula, Crysovalanto; Matteson, Lindsay; Mbarek, Hamdi; McArdle, Patrick F.; McMahon, George; Meddens, S.F.W.; Mihailov, Evelin; Miller, Mike; Missmer, Stacey A.; Monnereau, Claire; Most, van der Peter J.; Myhre, Ronny; Nalls, Mike A.; Nutile, Teresa; Kalafati, Ioanna Panagiota; Porcu, Eleonora; Prokopenko, Inga; Rajan, Kumar B.; Rich-Edwards, Janet; Rietveld, Cornelius A.; Robino, Antonietta; Rose, Lynda M.; Rueedi, Rico; Ryan, Kathleen A.; Saba, Yasaman; Schmidt, Daniel; Smith, Jennifer A.; Stolk, Lisette; Streeten, Elizabeth; Tönjes, Anke; Thorleifsson, Gudmar; Ulivi, Sheila; Wedenoja, Juho; Wellmann, Juergen; Willeit, Peter; Yao, Jie; Yengo, Loic; Zhao, Jing Hua; Zhao, Wei; Zhernakova, Daria V.; Amin, Najaf; Andrews, Howard; Balkau, Beverley; Barzilai, Nir; Bergmann, Sven; Biino, Ginevra; Bisgaard, Hans; Bønnelykke, Klaus; Boomsma, Dorret I.; Buring, Julie E.; Campbell, Harry; Cappellani, Stefania; Ciullo, Marina; Cox, Simon R.; Cucca, Francesco; Toniolo, Daniela; Davey-Smith, George; Deary, Ian J.; Dedoussis, George; Deloukas, Panos; Duijn, van Cornelia M.; Geus, de Eco J.C.; Eriksson, Johan G.; Evans, Denis A.; Faul, Jessica D.; Sala, Cinzia Felicita; Froguel, Philippe; Gasparini, Paolo; Girotto, Giorgia; Grabe, Hans-Jörgen; Greiser, Karin Halina; Groenen, Patrick J.F.; Haan, de Hugoline G.; Haerting, Johannes; Harris, Tamara B.; Heath, Andrew C.; Heikkilä, Kauko; Hofman, Albert; Homuth, Georg; Holliday, Elizabeth G.; Hopper, John; Hyppönen, Elina; Jacobsson, Bo; Jaddoe, Vincent W.V.; Johannesson, Magnus; Jugessur, Astanand; Kähönen, Mika; Kajantie, Eero; Kardia, Sharon L.R.; Keavney, Bernard; Kolcic, Ivana; Koponen, Päivikki; Kovacs, Peter; Kronenberg, Florian; Kutalik, Zoltan; Bianca, la Martina; Lachance, Genevieve; Iacono, William G.; Lai, Sandra; Lehtimäki, Terho; Liewald, David C.; Lindgren, Cecilia M.; Liu, Yongmei; Luben, Robert; Lucht, Michael; Luoto, Riitta; Magnus, Per; Magnusson, Patrik K.E.; Martin, Nicholas G.; McGue, Matt; McQuillan, Ruth; Medland, Sarah E.; Meisinger, Christa; Mellström, Dan; Metspalu, Andres; Traglia, Michela; Milani, Lili; Mitchell, Paul; Montgomery, Grant W.; Mook-Kanamori, Dennis; Mutsert, de Renée; Nohr, Ellen A.; Ohlsson, Claes; Olsen, Jørn; Ong, Ken K.; Paternoster, Lavinia; Pattie, Alison; Penninx, Brenda W.J.H.; Perola, Markus; Peyser, Patricia A.; Pirastu, Mario; Polasek, Ozren; Power, Chris; Kaprio, Jaakko; Raffel, Leslie J.; Räikkönen, Katri; Raitakari, Olli; Ridker, Paul M.; Ring, Susan M.; Roll, Kathryn; Rudan, Igor; Ruggiero, Daniela; Rujescu, Dan; Salomaa, Veikko; Schlessinger, David; Schmidt, Helena; Schmidt, Reinhold; Schupf, Nicole; Smit, Johannes; Sorice, Rossella; Spector, Tim D.; Starr, John M.; Stöckl, Doris; Strauch, Konstantin; Stumvoll, Michael; Swertz, Morris A.; Thorsteinsdottir, Unnur; Thurik, A.R.; Timpson, Nicholas J.; Tung, Joyce Y.; Uitterlinden, André G.; Vaccargiu, Simona; Viikari, Jorma; Vitart, Veronique; Völzke, Henry; Vollenweider, Peter; Vuckovic, Dragana; Waage, Johannes; Wagner, Gert G.; Wang, Jie Jin; Wareham, Nicholas J.; Weir, David R.; Willemsen, Gonneke; Willeit, Johann; Wright, Alan F.; Zondervan, Krina T.; Stefansson, Kari; Krueger, Robert F.; Lee, James J.; Benjamin, Daniel J.; Cesarini, David; Koellinger, Philipp D.; Hoed, den Marcel; Snieder, Harold; Mills, Melinda C.

    2016-01-01

    The genetic architecture of human reproductive behavior—age at first birth (AFB) and number of children ever born (NEB)—has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the

  19. Identifying Evidence-Based Practices for Behavior: Analysis of Studies Reviewed by the What Works Clearinghouse

    Science.gov (United States)

    LeRoy, Adam Scott

    2017-01-01

    Prior concerns have been raised about the ability of schools to access evidence-based practices, however, these practices are instrumental for addressing behavior concerns. This is particularly true at the secondary level, where students are more likely to be disproportionately identified for school removal. This review investigates studies of…

  20. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

    NARCIS (Netherlands)

    P.S. de Vries (Paul); D.I. Chasman (Daniel); M. Sabater-Lleal (Maria); M.-H. Chen (Ming-Huei); J.E. Huffman (Jennifer E.); M. Steri (Maristella); W. Tang (Weihong); A. Teumer (Alexander); R.E. Marioni (Riccardo); V. Grossmann (Vera); J.J. Hottenga (Jouke Jan); S. Trompet (Stella); M. Müller-Nurasyid (Martina); J.H. Zhao (Jing Hua); J. Brody (Jennifer); M.E. Kleber (Marcus); X. Guo (Xiuqing); J.J. Wang (Jie Jin); P. Auer (Paul); J. Attia (John); L.R. Yanek (Lisa); T.S. Ahluwalia (Tarunveer Singh); J. Lahti (Jari); C. Venturini (Cristina); T. Tanaka (Toshiko); L.F. Bielak (Lawrence F.); P.K. Joshi (Peter); A. Rocanin-Arjo (Ares); I. Kolcic (Ivana); P. Navarro (Pau); L.M. Rose (Lynda); C. Oldmeadow (Christopher); H. Riess (Helene); J. Mazur (Johanna); S. Basu (Saonli); A. Goel (Anuj); Q. Yang (Qiong); M. Ghanbari (Mohsen); Gonnekewillemsen; A. Rumley (Ann); E. Fiorillo (Edoardo); A.J. de Craen (Anton); A. Grotevendt (Anne); R.A. Scott (Robert); K.D. Taylor (Kent D.); G.E. Delgado (Graciela E.); J. Yao (Jie); A. Kifley (Annette); C. Kooperberg (Charles); Q. Qayyum (Rehan); L. Lopez (Lornam); T.L. Berentzen (Tina L.); K. Räikkönen (Katri); Massimomangino; S. Bandinelli (Stefania); P.A. Peyser (Patricia A.); S. Wild (Sarah); D.-A. Tregouet (David-Alexandre); A.F. Wright (Alan); J. Marten (Jonathan); T. Zemunik (Tatijana); A.C. Morrison (Alanna); B. Sennblad (Bengt); G.H. Tofler (Geoffrey); M.P.M. de Maat (Moniek); E.J.C. de Geus (Eco); G.D. Lowe (Gordon D.); M. Zoledziewska (Magdalena); N. Sattar (Naveed); H. Binder (Harald); U. Völker (Uwe); M. Waldenberger (Melanie); K.-T. Khaw (Kay-Tee); B. McKnight (Barbara); J. Huang (Jian); N.S. Jenny (Nancy); E.G. Holliday (Elizabeth); L. Qi (Lihong); M.G. Mcevoy (Mark G.); D.M. Becker (Diane); J.M. Starr (John); A.-P. Sarin; P.G. Hysi (Pirro); D.G. Hernandez (Dena); M.A. Jhun (Min A.); H. Campbell (Harry); A. Hamsten (Anders); F. Sarin (Fernando); W.L. McArdle (Wendy); P. Eline Slagboom; T. Zeller (Tanja); W. Koenig (Wolfgang); B. Psaty (Brucem); T. Haritunians (Talin); J. Liu (Jingmin); A. Palotie (Aarno); A.G. Uitterlinden (André); D.J. Stott (David J.); A. Hofman (Albert); O.H. Franco (Oscar); O. Polasek (Ozren); I. Rudan (Igor); P.-E. Morange (P.); J.F. Wilson (James F.); S.L. Kardia (Sharon L.r); L. Ferrucci (Luigi); T.D. Spector (Timothy); J.G. Eriksson (Johan G.); T. Hansen (Torben); I.J. Deary (Ian); L.C. Becker (Lewis); R.J. Scott (Rodney); P. Mitchell (Paul); W. März (Winfried); N.J. Wareham (Nick J.); A. Peters (Annette); A. Greinacher (Andreas); P.S. Wild (Philipp S.); J.W. Jukema (Jan Wouter); D.I. Boomsma (Dorret I.); C. Hayward (Caroline); F. Cucca (Francesco); R.P. Tracy (Russell); H. Watkins (Hugh); A.P. Reiner (Alex P.); A.R. Folsom (Aaron); P.M. Ridker (Paul); C.J. O'Donnell (Christopher J.); N.L. Smith (Nicholas L.); D.P. Strachan (David P.); A. Dehghan (Abbas)

    2016-01-01

    textabstractGenome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X-chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes

  1. A meta-analysis of 120 246 individuals identifies 18 new loci for fibrinogen concentration

    DEFF Research Database (Denmark)

    de Vries, Paul S; Chasman, Daniel I; Sabater-Lleal, Maria

    2016-01-01

    Genome-wide association studies have previously identified 23 genetic loci associated with circulating fibrinogen concentration. These studies used HapMap imputation and did not examine the X chromosome. 1000 Genomes imputation provides better coverage of uncommon variants, and includes indels. W...

  2. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer.

    NARCIS (Netherlands)

    Klein, Alison P; Wolpin, Brian M; Risch, Harvey A; Stolzenberg-Solomon, Rachael Z; Mocci, Evelina; Zhang, Mingfeng; Canzian, Federico; Childs, Erica J; Hoskins, Jason W; Jermusyk, Ashley; Zhong, Jun; Sund, Malin; Talar-Wojnarowska, Renata; Tavano, Francesca; Thornquist, Mark D; Tobias, Geoffrey S; Van Den Eeden, Stephen K; Vashist, Yogesh; Visvanathan, Kala; Vodicka, Pavel; Wactawski-Wende, Jean; Chen, Fei; Wang, Zhaoming; Wentzensen, Nicolas; White, Emily; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Kraft, Peter; Li, Donghui; Chanock, Stephen; Albanes, Demetrius; Obazee, Ofure; Petersen, Gloria M; Amundadottir, Laufey T; Andreotti, Gabriella; Arslan, Alan A; Babic, Ana; Bamlet, William R; Beane-Freeman, Laura; Berndt, Sonja I; Blackford, Amanda; Borges, Michael; Borgida, Ayelet; Bracci, Paige M; Brais, Lauren; Brennan, Paul; Brenner, Hermann; Bueno-de-Mesquita, Bas; Buring, Julie; Campa, Daniele; Capurso, Gabriele; Cavestro, Giulia Martina; Chaffee, Kari G; Chung, Charles C; Cleary, Sean; Cotterchio, Michelle; Dijk, Frederike; Duell, Eric J; Foretova, Lenka; Fuchs, Charles; Funel, Niccola; Gallinger, Steven; M Gaziano, J Michael; Gazouli, Maria; Giles, Graham G; Giovannucci, Edward; Goggins, Michael; Goodman, Gary E; Goodman, Phyllis J; Hackert, Thilo; Haiman, Christopher; Hartge, Patricia; Hasan, Manal; Hegyi, Peter; Helzlsouer, Kathy J; Herman, Joseph; Holcatova, Ivana; Holly, Elizabeth A; Hoover, Robert; Hung, Rayjean J; Jacobs, Eric J; Jamroziak, Krzysztof; Janout, Vladimir; Kaaks, Rudolf; Khaw, Kay-Tee; Klein, Eric A; Kogevinas, Manolis; Kooperberg, Charles; Kulke, Matthew H; Kupcinskas, Juozas; Kurtz, Robert J; Laheru, Daniel; Landi, Stefano; Lawlor, Rita T; Lee, I-Min; LeMarchand, Loic; Lu, Lingeng; Malats, Núria; Mambrini, Andrea; Mannisto, Satu; Milne, Roger L; Mohelníková-Duchoňová, Beatrice; Neale, Rachel E; Neoptolemos, John P; Oberg, Ann L; Olson, Sara H; Orlow, Irene; Pasquali, Claudio; Patel, Alpa V; Peters, Ulrike; Pezzilli, Raffaele; Porta, Miquel; Real, Francisco X; Rothman, Nathaniel; Scelo, Ghislaine; Sesso, Howard D; Severi, Gianluca; Shu, Xiao-Ou; Silverman, Debra; Smith, Jill P; Soucek, Pavel

    2018-01-01

    In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic

  3. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

    NARCIS (Netherlands)

    Klein, Alison P.; Wolpin, Brian M.; Risch, Harvey A.; Stolzenberg-Solomon, Rachael Z.; Mocci, Evelina; Zhang, Mingfeng; Canzian, Federico; Childs, Erica J.; Hoskins, Jason W.; Jermusyk, Ashley; Zhong, Jun; Chen, Fei; Albanes, Demetrius; Andreotti, Gabriella; Arslan, Alan A.; Babic, Ana; Bamlet, William R.; Beane-Freeman, Laura; Berndt, Sonja I.; Blackford, Amanda; Borges, Michael; Borgida, Ayelet; Bracci, Paige M.; Brais, Lauren; Brennan, Paul; Brenner, Hermann; Bueno-de-Mesquita, Bas; Buring, Julie; Campa, Daniele; Capurso, Gabriele; Cavestro, Giulia Martina; Chaffee, Kari G.; Chung, Charles C.; Cleary, Sean; Cotterchio, Michelle; Dijk, Frederike; Duell, Eric J.; Foretova, Lenka; Fuchs, Charles; Funel, Niccola; Gallinger, Steven; M Gaziano, J. Michael; Gazouli, Maria; Giles, Graham G.; Giovannucci, Edward; Goggins, Michael; Goodman, Gary E.; Goodman, Phyllis J.; Hackert, Thilo; Haiman, Christopher; Hartge, Patricia; Hasan, Manal; Hegyi, Peter; Helzlsouer, Kathy J.; Herman, Joseph; Holcatova, Ivana; Holly, Elizabeth A.; Hoover, Robert; Hung, Rayjean J.; Jacobs, Eric J.; Jamroziak, Krzysztof; Janout, Vladimir; Kaaks, Rudolf; Khaw, Kay-Tee; Klein, Eric A.; Kogevinas, Manolis; Kooperberg, Charles; Kulke, Matthew H.; Kupcinskas, Juozas; Kurtz, Robert J.; Laheru, Daniel; Landi, Stefano; Lawlor, Rita T.; Lee, I.-Min; Lemarchand, Loic; Lu, Lingeng; Malats, Núria; Mambrini, Andrea; Mannisto, Satu; Milne, Roger L.; Mohelníková-Duchoňová, Beatrice; Neale, Rachel E.; Neoptolemos, John P.; Oberg, Ann L.; Olson, Sara H.; Orlow, Irene; Pasquali, Claudio; Patel, Alpa V.; Peters, Ulrike; Pezzilli, Raffaele; Porta, Miquel; Real, Francisco X.; Rothman, Nathaniel; Scelo, Ghislaine; Sesso, Howard D.; Severi, Gianluca; Shu, Xiao-Ou; Silverman, Debra; Smith, Jill P.; Soucek, Pavel; Sund, Malin; Talar-Wojnarowska, Renata; Tavano, Francesca; Thornquist, Mark D.; Tobias, Geoffrey S.; van den Eeden, Stephen K.; Vashist, Yogesh; Visvanathan, Kala; Vodicka, Pavel; Wactawski-Wende, Jean; Wang, Zhaoming; Wentzensen, Nicolas; White, Emily; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Zheng, Wei; Kraft, Peter; Li, Donghui; Chanock, Stephen; Obazee, Ofure; Petersen, Gloria M.; Amundadottir, Laufey T.

    2018-01-01

    In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic

  4. Identifying Professional Teaching Standards Using Rasch Model Analysis: The Case of Northern Cyprus

    Science.gov (United States)

    Alibaba Erden, Hale; Özer, Bekir

    2013-01-01

    Problem Statement: The Teacher's-Act defined for the state-school teachers of North Cyprus shows that teachers are not selected according to any specific standards. In North Cyprus, apart from the exam topics defined at the teacher's exam regulations, there is not any kind of identified standard for teachers. Training qualified teachers based upon…

  5. Genomic analysis identifies candidate pathogenic variants in 9 of 18 patients with unexplained West syndrome.

    Science.gov (United States)

    Hino-Fukuyo, Naomi; Kikuchi, Atsuo; Arai-Ichinoi, Natsuko; Niihori, Tetsuya; Sato, Ryo; Suzuki, Tasuku; Kudo, Hiroki; Sato, Yuko; Nakayama, Tojo; Kakisaka, Yosuke; Kubota, Yuki; Kobayashi, Tomoko; Funayama, Ryo; Nakayama, Keiko; Uematsu, Mitsugu; Aoki, Yoko; Haginoya, Kazuhiro; Kure, Shigeo

    2015-06-01

    West syndrome, which is narrowly defined as infantile spasms that occur in clusters and hypsarrhythmia on EEG, is the most common early-onset epileptic encephalopathy (EOEE). Patients with West syndrome may have clear etiologies, including perinatal events, infections, gross chromosomal abnormalities, or cases followed by other EOEEs. However, the genetic etiology of most cases of West syndrome remains unexplained. DNA from 18 patients with unexplained West syndrome was subjected to microarray-based comparative genomic hybridization (array CGH), followed by trio-based whole-exome sequencing in 14 unsolved families. We identified candidate pathogenic variants in 50% of the patients (n = 9/18). The array CGH revealed candidate pathogenic copy number variations in four cases (22%, 4/18), including an Xq28 duplication, a 16p11.2 deletion, a 16p13.1 deletion and a 19p13.2 deletion disrupting CACNA1A. Whole-exome sequencing identified candidate mutations in known epilepsy genes in five cases (36%, 5/14). Three candidate de novo mutations were identified in three cases, with two mutations occurring in two new candidate genes (NR2F1 and CACNA2D1) (21%, 3/14). Hemizygous candidate mutations in ALG13 and BRWD3 were identified in the other two cases (14%, 2/14). Evaluating a panel of 67 known EOEE genes failed to identify significant mutations. Despite the heterogeneity of unexplained West syndrome, the combination of array CGH and whole-exome sequencing is an effective means of evaluating the genetic background in unexplained West syndrome. We provide additional evidence for NR2F1 as a causative gene and for CACNA2D1 and BRWD3 as candidate genes for West syndrome.

  6. VAN: an R package for identifying biologically perturbed networks via differential variability analysis

    OpenAIRE

    Jayaswal, Vivek; Schramm, Sarah-Jane; Mann, Graham J; Wilkins, Marc R; Yang, Yee Hwa

    2013-01-01

    Background Large-scale molecular interaction networks are dynamic in nature and are of special interest in the analysis of complex diseases, which are characterized by network-level perturbations rather than changes in individual genes/proteins. The methods developed for the identification of differentially expressed genes or gene sets are not suitable for network-level analyses. Consequently, bioinformatics approaches that enable a joint analysis of high-throughput transcriptomics datasets a...

  7. Biomarker Analysis of Samples Visually Identified as Microbial in the Eocene Green River Formation: An Analogue for Mars.

    Science.gov (United States)

    Olcott Marshall, Alison; Cestari, Nicholas A

    2015-09-01

    One of the major exploration targets for current and future Mars missions are lithofacies suggestive of biotic activity. Although such lithofacies are not confirmation of biotic activity, they provide a way to identify samples for further analyses. To test the efficacy of this approach, we identified carbonate samples from the Eocene Green River Formation as "microbial" or "non-microbial" based on the macroscale morphology of their laminations. These samples were then crushed and analyzed by gas chromatography/mass spectroscopy (GC/MS) to determine their lipid biomarker composition. GC/MS analysis revealed that carbonates visually identified as "microbial" contained a higher concentration of more diverse biomarkers than those identified as "non-microbial," suggesting that this could be a viable detection strategy for selecting samples for further analysis or caching on Mars.

  8. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

    NARCIS (Netherlands)

    C.E. Elks (Cathy); J.R.B. Perry (John); P. Sulem (Patrick); D.I. Chasman (Daniel); N. Franceschini (Nora); C. He (Chunyan); K.L. Lunetta (Kathryn); J.A. Visser (Jenny); E.M. Byrne (Enda); D.L. Cousminer (Diana); D.F. Gudbjartsson (Daniel); T. Esko (Tõnu); B. Feenstra (Bjarke); J.J. Hottenga (Jouke Jan); D.L. Koller (Daniel); Z. Kutalik (Zoltán); P. Lin (Peng); M. Mangino (Massimo); M. Marongiu (Mara); P.F. McArdle (Patrick); A.V. Smith (Albert Vernon); L. Stolk (Lisette); S. van Wingerden (Sophie); J.H. Zhao (Jing Hua); E. Albrecht (Eva); T. Corre (Tanguy); E. Ingelsson (Erik); C. Hayward (Caroline); P.K. Magnusson (Patrik); S. Ulivi (Shelia); N.M. Warrington (Nicole); L. Zgaga (Lina); H. Alavere (Helene); N. Amin (Najaf); T. Aspelund (Thor); S. Bandinelli (Stefania); I.E. Barroso (Inês); G. Berenson (Gerald); S.M. Bergmann (Sven); H. Blackburn (Hannah); E.A. Boerwinkle (Eric); J.E. Buring (Julie); F. Busonero; H. Campbell (Harry); S.J. Chanock (Stephen); W. Chen (Wei); M. Cornelis (Marilyn); D.J. Couper (David); A.D. Coviello (Andrea); P. d' Adamo (Pio); U. de Faire (Ulf); E.J.C. de Geus (Eco); P. Deloukas (Panagiotis); A. Döring (Angela); D.F. Easton (Douglas); G. Eiriksdottir (Gudny); V. Emilsson (Valur); J.G. Eriksson (Johan); L. Ferrucci (Luigi); A.R. Folsom (Aaron); T. Foroud (Tatiana); M. Garcia (Melissa); P. Gasparini (Paolo); F. Geller (Frank); C. Gieger (Christian); V. Gudnason (Vilmundur); A.S. Hall (Alistair); S.E. Hankinson (Susan); L. Ferreli (Liana); A.C. Heath (Andrew); D.G. Hernandez (Dena); A. Hofman (Albert); F.B. Hu (Frank); T. Illig (Thomas); M.R. Järvelin; A.D. Johnson (Andrew); D. Karasik (David); K-T. Khaw (Kay-Tee); D.P. Kiel (Douglas); T.O. Kilpelänen (Tuomas); I. Kolcic (Ivana); P. Kraft (Peter); L.J. Launer (Lenore); J.S.E. Laven (Joop); S. Li (Shengxu); J. Liu (Jianjun); D. Levy (Daniel); N.G. Martin (Nicholas); M. Melbye (Mads); V. Mooser (Vincent); J.C. Murray (Jeffrey); M.A. Nalls (Michael); P. Navarro (Pau); M. Nelis (Mari); A.R. Ness (Andrew); K. Northstone (Kate); B.A. Oostra (Ben); M. Peacock (Munro); C. Palmer (Cameron); A. Palotie (Aarno); G. Paré (Guillaume); A.N. Parker (Alex); N.L. Pedersen (Nancy); L. Peltonen (Leena Johanna); C.E. Pennell (Craig); P.D.P. Pharoah (Paul); O. Polasek (Ozren); A.S. Plump (Andrew); A. Pouta (Anneli); E. Porcu (Eleonora); T. Rafnar (Thorunn); J.P. Rice (John); S.M. Ring (Susan); F. Rivadeneira Ramirez (Fernando); I. Rudan (Igor); C. Sala (Cinzia); V. Salomaa (Veikko); S. Sanna (Serena); D. Schlessinger; N.J. Schork (Nicholas); A. Scuteri (Angelo); A.V. Segrè (Ayellet); A.R. Shuldiner (Alan); N. Soranzo (Nicole); U. Sovio (Ulla); S.R. Srinivasan (Sathanur); D.P. Strachan (David); M.L. Tammesoo; E. Tikkanen (Emmi); D. Toniolo (Daniela); K. Tsui (Kim); L. Tryggvadottir (Laufey); J.P. Tyrer (Jonathan); M. Uda (Manuela); R.M. van Dam (Rob); J.B.J. van Meurs (Joyce); P. Vollenweider (Peter); G. Waeber (Gérard); N.J. Wareham (Nick); D. Waterworth (Dawn); H.E. Wichmann (Heinz Erich); G.A.H.M. Willemsen (Gonneke); J.F. Wilson (James); A.F. Wright (Alan); L. Young (Lauren); G. Zhai (Guangju); W.V. Zhuang; L.J. Bierut (Laura); D.I. Boomsma (Dorret); H.A. Boyd (Heather); L. Crisponi (Laura); E.W. Demerath (Ellen); P. Tikka-Kleemola (Päivi); M.J. Econs (Michael); T.B. Harris (Tamara); D. Hunter (David); R.J.F. Loos (Ruth); A. Metspalu (Andres); G.W. Montgomery (Grant); P.M. Ridker (Paul); T.D. Spector (Tim); E.A. Streeten (Elizabeth); K. Stefansson (Kari); U. Thorsteinsdottir (Unnur); A.G. Uitterlinden (André); E. Widen (Elisabeth); J. Murabito (Joanne); K. Ong (Ken); M.N. Weedon (Michael)

    2010-01-01

    textabstractTo identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10 -60) and 9q31.2 (P = 2.2 × 10 -33), we identified 30

  9. Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

    DEFF Research Database (Denmark)

    Elks, Cathy E; Perry, John R B; Sulem, Patrick

    2010-01-01

    To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarc...

  10. Differentially expressed genes in pancreatic ductal adenocarcinomas identified through serial analysis of gene expression

    DEFF Research Database (Denmark)

    Hustinx, Steven R; Cao, Dengfeng; Maitra, Anirban

    2004-01-01

    genome and better biocomputational techniques have substantially improved the assignment of differentially expressed SAGE "tags" to human genes. These improvements have provided us with an opportunity to re-evaluate global gene expression in pancreatic cancer using existing SAGE libraries. SAGE libraries...... generated from six pancreatic cancers were compared to SAGE libraries generated from 11 non-neoplastic tissues. Compared to normal tissue libraries, we identified 453 SAGE tags as differentially expressed in pancreatic cancer, including 395 that mapped to known genes and 58 "uncharacterized" tags....... Of the 395 SAGE tags assigned to known genes, 223 were overexpressed in pancreatic cancer, and 172 were underexpressed. In order to map the 58 uncharacterized differentially expressed SAGE tags to genes, we used a newly developed resource called TAGmapper (http://tagmapper.ibioinformatics.org), to identify...

  11. Phosphoproteomic Analysis Identifies Signaling Pathways Regulated by Curcumin in Human Colon Cancer Cells.

    Science.gov (United States)

    Sato, Tatsuhiro; Higuchi, Yutaka; Shibagaki, Yoshio; Hattori, Seisuke

    2017-09-01

    Curcumin, a major polyphenol of the spice turmeric, acts as a potent chemopreventive and chemotherapeutic agent in several cancer types, including colon cancer. Although various proteins have been shown to be affected by curcumin, how curcumin exerts its anticancer activity is not fully understood. Phosphoproteomic analyses were performed using SW480 and SW620 human colon cancer cells to identify curcumin-affected signaling pathways. Curcumin inhibited the growth of the two cell lines in a dose-dependent manner. Thirty-nine curcumin-regulated phosphoproteins were identified, five of which are involved in cancer signaling pathways. Detailed analyses revealed that the mTORC1 and p53 signaling pathways are main targets of curcumin. Our results provide insight into the molecular mechanisms of the anticancer activities of curcumin and future molecular targets for its clinical application. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

    Science.gov (United States)

    Barban, Nicola; Jansen, Rick; de Vlaming, Ronald; Vaez, Ahmad; Mandemakers, Jornt J; Tropf, Felix C; Shen, Xia; Wilson, James F; Chasman, Daniel I; Nolte, Ilja M; Tragante, Vinicius; van der Laan, Sander W; Perry, John R B; Kong, Augustine; Ahluwalia, Tarunveer S; Albrecht, Eva; Yerges-Armstrong, Laura; Atzmon, Gil; Auro, Kirsi; Ayers, Kristin; Bakshi, Andrew; Ben-Avraham, Danny; Berger, Klaus; Bergman, Aviv; Bertram, Lars; Bielak, Lawrence F; Bjornsdottir, Gyda; Bonder, Marc Jan; Broer, Linda; Bui, Minh; Barbieri, Caterina; Cavadino, Alana; Chavarro, Jorge E; Turman, Constance; Concas, Maria Pina; Cordell, Heather J; Davies, Gail; Eibich, Peter; Eriksson, Nicholas; Esko, Tõnu; Eriksson, Joel; Falahi, Fahimeh; Felix, Janine F; Fontana, Mark Alan; Franke, Lude; Gandin, Ilaria; Gaskins, Audrey J; Gieger, Christian; Gunderson, Erica P; Guo, Xiuqing; Hayward, Caroline; He, Chunyan; Hofer, Edith; Huang, Hongyan; Joshi, Peter K; Kanoni, Stavroula; Karlsson, Robert; Kiechl, Stefan; Kifley, Annette; Kluttig, Alexander; Kraft, Peter; Lagou, Vasiliki; Lecoeur, Cecile; Lahti, Jari; Li-Gao, Ruifang; Lind, Penelope A; Liu, Tian; Makalic, Enes; Mamasoula, Crysovalanto; Matteson, Lindsay; Mbarek, Hamdi; McArdle, Patrick F; McMahon, George; Meddens, S Fleur W; Mihailov, Evelin; Miller, Mike; Missmer, Stacey A; Monnereau, Claire; van der Most, Peter J; Myhre, Ronny; Nalls, Mike A; Nutile, Teresa; Kalafati, Ioanna Panagiota; Porcu, Eleonora; Prokopenko, Inga; Rajan, Kumar B; Rich-Edwards, Janet; Rietveld, Cornelius A; Robino, Antonietta; Rose, Lynda M; Rueedi, Rico; Ryan, Kathleen A; Saba, Yasaman; Schmidt, Daniel; Smith, Jennifer A; Stolk, Lisette; Streeten, Elizabeth; Tönjes, Anke; Thorleifsson, Gudmar; Ulivi, Sheila; Wedenoja, Juho; Wellmann, Juergen; Willeit, Peter; Yao, Jie; Yengo, Loic; Zhao, Jing Hua; Zhao, Wei; Zhernakova, Daria V; Amin, Najaf; Andrews, Howard; Balkau, Beverley; Barzilai, Nir; Bergmann, Sven; Biino, Ginevra; Bisgaard, Hans; Bønnelykke, Klaus; Boomsma, Dorret I; Buring, Julie E; Campbell, Harry; Cappellani, Stefania; Ciullo, Marina; Cox, Simon R; Cucca, Francesco; Toniolo, Daniela; Davey-Smith, George; Deary, Ian J; Dedoussis, George; Deloukas, Panos; van Duijn, Cornelia M; de Geus, Eco J C; Eriksson, Johan G; Evans, Denis A; Faul, Jessica D; Sala, Cinzia Felicita; Froguel, Philippe; Gasparini, Paolo; Girotto, Giorgia; Grabe, Hans-Jörgen; Greiser, Karin Halina; Groenen, Patrick J F; de Haan, Hugoline G; Haerting, Johannes; Harris, Tamara B; Heath, Andrew C; Heikkilä, Kauko; Hofman, Albert; Homuth, Georg; Holliday, Elizabeth G; Hopper, John; Hyppönen, Elina; Jacobsson, Bo; Jaddoe, Vincent W V; Johannesson, Magnus; Jugessur, Astanand; Kähönen, Mika; Kajantie, Eero; Kardia, Sharon L R; Keavney, Bernard; Kolcic, Ivana; Koponen, Päivikki; Kovacs, Peter; Kronenberg, Florian; Kutalik, Zoltan; La Bianca, Martina; Lachance, Genevieve; Iacono, William G; Lai, Sandra; Lehtimäki, Terho; Liewald, David C; Lindgren, Cecilia M; Liu, Yongmei; Luben, Robert; Lucht, Michael; Luoto, Riitta; Magnus, Per; Magnusson, Patrik K E; Martin, Nicholas G; McGue, Matt; McQuillan, Ruth; Medland, Sarah E; Meisinger, Christa; Mellström, Dan; Metspalu, Andres; Traglia, Michela; Milani, Lili; Mitchell, Paul; Montgomery, Grant W; Mook-Kanamori, Dennis; de Mutsert, Renée; Nohr, Ellen A; Ohlsson, Claes; Olsen, Jørn; Ong, Ken K; Paternoster, Lavinia; Pattie, Alison; Penninx, Brenda W J H; Perola, Markus; Peyser, Patricia A; Pirastu, Mario; Polasek, Ozren; Power, Chris; Kaprio, Jaakko; Raffel, Leslie J; Räikkönen, Katri; Raitakari, Olli; Ridker, Paul M; Ring, Susan M; Roll, Kathryn; Rudan, Igor; Ruggiero, Daniela; Rujescu, Dan; Salomaa, Veikko; Schlessinger, David; Schmidt, Helena; Schmidt, Reinhold; Schupf, Nicole; Smit, Johannes; Sorice, Rossella; Spector, Tim D; Starr, John M; Stöckl, Doris; Strauch, Konstantin; Stumvoll, Michael; Swertz, Morris A; Thorsteinsdottir, Unnur; Thurik, A Roy; Timpson, Nicholas J; Tung, Joyce Y; Uitterlinden, André G; Vaccargiu, Simona; Viikari, Jorma; Vitart, Veronique; Völzke, Henry; Vollenweider, Peter; Vuckovic, Dragana; Waage, Johannes; Wagner, Gert G; Wang, Jie Jin; Wareham, Nicholas J; Weir, David R; Willemsen, Gonneke; Willeit, Johann; Wright, Alan F; Zondervan, Krina T; Stefansson, Kari; Krueger, Robert F; Lee, James J; Benjamin, Daniel J; Cesarini, David; Koellinger, Philipp D; den Hoed, Marcel; Snieder, Harold; Mills, Melinda C

    2016-12-01

    The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits.

  13. Genome-wide analysis identifies 12 loci influencing human reproductive behavior

    Science.gov (United States)

    Barban, Nicola; Jansen, Rick; de Vlaming, Ronald; Vaez, Ahmad; Mandemakers, Jornt J.; Tropf, Felix C.; Shen, Xia; Wilson, James F.; Chasman, Daniel I.; Nolte, Ilja M.; Tragante, Vinicius; van der Laan, Sander W.; Perry, John R. B.; Kong, Augustine; Ahluwalia, Tarunveer; Albrecht, Eva; Yerges-Armstrong, Laura; Atzmon, Gil; Auro, Kirsi; Ayers, Kristin; Bakshi, Andrew; Ben-Avraham, Danny; Berger, Klaus; Bergman, Aviv; Bertram, Lars; Bielak, Lawrence F.; Bjornsdottir, Gyda; Bonder, Marc Jan; Broer, Linda; Bui, Minh; Barbieri, Caterina; Cavadino, Alana; Chavarro, Jorge E; Turman, Constance; Concas, Maria Pina; Cordell, Heather J.; Davies, Gail; Eibich, Peter; Eriksson, Nicholas; Esko, Tõnu; Eriksson, Joel; Falahi, Fahimeh; Felix, Janine F.; Fontana, Mark Alan; Franke, Lude; Gandin, Ilaria; Gaskins, Audrey J.; Gieger, Christian; Gunderson, Erica P.; Guo, Xiuqing; Hayward, Caroline; He, Chunyan; Hofer, Edith; Huang, Hongyan; Joshi, Peter K.; Kanoni, Stavroula; Karlsson, Robert; Kiechl, Stefan; Kifley, Annette; Kluttig, Alexander; Kraft, Peter; Lagou, Vasiliki; Lecoeur, Cecile; Lahti, Jari; Li-Gao, Ruifang; Lind, Penelope A.; Liu, Tian; Makalic, Enes; Mamasoula, Crysovalanto; Matteson, Lindsay; Mbarek, Hamdi; McArdle, Patrick F.; McMahon, George; Meddens, S. Fleur W.; Mihailov, Evelin; Miller, Mike; Missmer, Stacey A.; Monnereau, Claire; van der Most, Peter J.; Myhre, Ronny; Nalls, Mike A.; Nutile, Teresa; Panagiota, Kalafati Ioanna; Porcu, Eleonora; Prokopenko, Inga; Rajan, Kumar B.; Rich-Edwards, Janet; Rietveld, Cornelius A.; Robino, Antonietta; Rose, Lynda M.; Rueedi, Rico; Ryan, Kathy; Saba, Yasaman; Schmidt, Daniel; Smith, Jennifer A.; Stolk, Lisette; Streeten, Elizabeth; Tonjes, Anke; Thorleifsson, Gudmar; Ulivi, Sheila; Wedenoja, Juho; Wellmann, Juergen; Willeit, Peter; Yao, Jie; Yengo, Loic; Zhao, Jing Hua; Zhao, Wei; Zhernakova, Daria V.; Amin, Najaf; Andrews, Howard; Balkau, Beverley; Barzilai, Nir; Bergmann, Sven; Biino, Ginevra; Bisgaard, Hans; Bønnelykke, Klaus; Boomsma, Dorret I.; Buring, Julie E.; Campbell, Harry; Cappellani, Stefania; Ciullo, Marina; Cox, Simon R.; Cucca, Francesco; Daniela, Toniolo; Davey-Smith, George; Deary, Ian J.; Dedoussis, George; Deloukas, Panos; van Duijn, Cornelia M.; de Geus, Eco JC.; Eriksson, Johan G.; Evans, Denis A.; Faul, Jessica D.; Felicita, Sala Cinzia; Froguel, Philippe; Gasparini, Paolo; Girotto, Giorgia; Grabe, Hans-Jörgen; Greiser, Karin Halina; Groenen, Patrick J.F.; de Haan, Hugoline G.; Haerting, Johannes; Harris, Tamara B.; Heath, Andrew C.; Heikkilä, Kauko; Hofman, Albert; Homuth, Georg; Holliday, Elizabeth G; Hopper, John; Hypponen, Elina; Jacobsson, Bo; Jaddoe, Vincent W. V.; Johannesson, Magnus; Jugessur, Astanand; Kähönen, Mika; Kajantie, Eero; Kardia, Sharon L.R.; Keavney, Bernard; Kolcic, Ivana; Koponen, Päivikki; Kovacs, Peter; Kronenberg, Florian; Kutalik, Zoltan; La Bianca, Martina; Lachance, Genevieve; Iacono, William; Lai, Sandra; Lehtimäki, Terho; Liewald, David C; Lindgren, Cecilia; Liu, Yongmei; Luben, Robert; Lucht, Michael; Luoto, Riitta; Magnus, Per; Magnusson, Patrik K.E.; Martin, Nicholas G.; McGue, Matt; McQuillan, Ruth; Medland, Sarah E.; Meisinger, Christa; Mellström, Dan; Metspalu, Andres; Michela, Traglia; Milani, Lili; Mitchell, Paul; Montgomery, Grant W.; Mook-Kanamori, Dennis; de Mutsert, Renée; Nohr, Ellen A; Ohlsson, Claes; Olsen, Jørn; Ong, Ken K.; Paternoster, Lavinia; Pattie, Alison; Penninx, Brenda WJH; Perola, Markus; Peyser, Patricia A.; Pirastu, Mario; Polasek, Ozren; Power, Chris; Kaprio, Jaakko; Raffel, Leslie J.; Räikkönen, Katri; Raitakari, Olli; Ridker, Paul M.; Ring, Susan M.; Roll, Kathryn; Rudan, Igor; Ruggiero, Daniela; Rujescu, Dan; Salomaa, Veikko; Schlessinger, David; Schmidt, Helena; Schmidt, Reinhold; Schupf, Nicole; Smit, Johannes; Sorice, Rossella; Spector, Tim D.; Starr, John M.; Stöckl, Doris; Strauch, Konstantin; Stumvoll, Michael; Swertz, Morris A.; Thorsteinsdottir, Unnur; Thurik, A. Roy; Timpson, Nicholas J.; Tönjes, Anke; Tung, Joyce Y.; Uitterlinden, André G.; Vaccargiu, Simona; Viikari, Jorma; Vitart, Veronique; Völzke, Henry; Vollenweider, Peter; Vuckovic, Dragana; Waage, Johannes; Wagner, Gert G.; Wang, Jie Jin; Wareham, Nicholas J.; Weir, David R.; Willemsen, Gonneke; Willeit, Johann; Wright, Alan F.; Zondervan, Krina T.; Stefansson, Kari; Krueger, Robert F.; Lee, James J.; Benjamin, Daniel J.; Cesarini, David; Koellinger, Philipp D.; den Hoed, Marcel; Snieder, Harold; Mills, Melinda C.

    2017-01-01

    The genetic architecture of human reproductive behavior – age at first birth (AFB) and number of children ever born (NEB) – has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified and the underlying mechanisms of AFB and NEB are poorly understood. We report the largest genome-wide association study to date of both sexes including 251,151 individuals for AFB and 343,072 for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study, and four additional loci in a gene-based effort. These loci harbor genes that are likely to play a role – either directly or by affecting non-local gene expression – in human reproduction and infertility, thereby increasing our understanding of these complex traits. PMID:27798627

  14. GWAS meta-analysis and replication identifies three new susceptibility loci for ovarian cancer

    DEFF Research Database (Denmark)

    Pharoah, Paul D P; Tsai, Ya-Yu; Ramus, Susan J

    2013-01-01

    associations close to genome-wide significance and identified three loci newly associated with risk: two loci associated with all EOC subtypes at 8q21 (rs11782652, P = 5.5 × 10−9) and 10p12 (rs1243180, P = 1.8 × 10−8) and another locus specific to the serous subtype at 17q12 (rs757210, P = 8.1 × 10...

  15. Cross-database analysis to identify relationships between aircraft accidents and incidents

    Science.gov (United States)

    Nazeri, Zohreh

    Air transportation systems are designed to ensure that aircraft accidents are rare events. To minimize these accidents, factors causing or contributing to accidents must be understood and prevented. Despite many efforts by the aviation safety community to reduce the accidents, accident rates have been stable for decades. One explanation could be that direct and obvious causes that previously occurred with a relatively high frequency have already been addressed over the past few decades. What remains is a much more difficult challenge---identifying less obvious causes, combinations of factors that, when occurring together, may potentially lead to an accident. Contributions of this research to the aviation safety community are two-fold: (1) The analyses conducted in this research, identified significant accident factors. Detection and prevention of these factors, could prevent potential future accidents. The holistic study made it possible to compare the factors in a common framework. The identified factors were compared and ranked in terms of their likelihood of being involved in accidents. Corrective actions by the FAA Aviation Safety Oversight (ASO), air carrier safety offices, and the aviation safety community in general, could target the high-ranked factors first. The aviation safety community can also use the identified factors as a benchmark to measure and compare safety levels in different periods and/or at different regions. (2) The methodology established in this study, can be used by researchers in future studies. By applying this methodology to the safety data, areas prone to future accidents can be detected and addressed. Air carriers can apply this methodology to analyze their proprietary data and find detailed safety factors specific to their operations. The Factor Support Ratio metric introduced in this research, can be used to measure and compare different safety factors. (Abstract shortened by UMI.)

  16. Root cause analysis of transfusion error: identifying causes to implement changes.

    Science.gov (United States)

    Elhence, Priti; Veena, S; Sharma, Raj Kumar; Chaudhary, R K

    2010-12-01

    As part of ongoing efforts to improve transfusion safety, an error reporting system was implemented in our hospital-based transfusion medicine unit at a tertiary care medical institute. This system is based on Medical Event Reporting System-Transfusion Medicine (MERS-TM) and collects data on all near miss, no harm, and misadventures related to the transfusion process. Root cause analyses of one such innocuous appearing error demonstrate how weaknesses in the system can be identified to make necessary changes to achieve transfusion safety. The reported error was investigated, classified, coded, and analyzed using MERS-TM prototype, modified and adopted for our institute. The consequent error was a "mistransfusion" but a "no-harm event" as the transfused unit was of the same blood group as the patient. It was a high event severity level error (level 1). Multiple errors preceded the final error at various functional locations in the transfusion process. Human, organizational, and patient-related factors were identified as root causes and corrective actions were initiated to prevent future occurrences. This case illustrates the usefulness of having an error reporting system in hospitals to highlight human and system failures associated with transfusion that may otherwise go unnoticed. Areas can be identified where resources need to be targeted to improve patient safety. © 2010 American Association of Blood Banks.

  17. A strategy to identify housekeeping genes suitable for analysis in breast cancer diseases.

    Science.gov (United States)

    Tilli, Tatiana M; Castro, Cláudio da Silva; Tuszynski, Jack A; Carels, Nicolas

    2016-08-15

    The selection of suitable internal control genes is crucial for proper interpretation of real-time PCR data. Here we outline a strategy to identify housekeeping genes that could serve as suitable internal control for comparative analyses of gene expression data in breast cancer cell lines and tissues obtained by high throughput sequencing and quantitative real-time PCR (qRT-PCR). The strategy proposed includes the large-scale screening of potential candidate reference genes from RNA-seq data as well as their validation by qRT-PCR, and careful examination of reference data from the International Cancer Genome Consortium, The Cancer Genome Atlas and Gene Expression Omnibus repositories. The identified set of reference genes, also called novel housekeeping genes that includes CCSER2, SYMPK, ANKRD17 and PUM1, proved to be less variable and thus potentially more accurate for research and clinical analyses of breast cell lines and tissue samples compared to the traditional housekeeping genes used to this end. These results highlight the importance of a massive evaluation of housekeeping genes for their relevance as internal control for optimized intra- and inter-assay comparison of gene expression. We developed a strategy to identify and evaluate the significance of housekeeping genes as internal control for the intra- and inter-assay comparison of gene expression in breast cancer that could be applied to other tumor types and diseases.

  18. Systems Genetics Analysis to Identify the Genetic Modulation of a Glaucoma-Associated Gene.

    Science.gov (United States)

    Chintalapudi, Sumana R; Jablonski, Monica M

    2017-01-01

    Loss of retinal ganglion cells (RGCs) is one of the hallmarks of retinal neurodegenerative diseases, glaucoma being one of the most common. Recently, γ-synuclein (SNCG) was shown to be highly expressed in the somas and axons of RGCs. In various mouse models of glaucoma, downregulation of Sncg gene expression correlates with RGC loss. To investigate the regulation of Sncg in RGCs, we used a systems genetics approach to identify a gene that modulates the expression of Sncg, followed by confirmatory studies in both healthy and diseased retinas. We found that chromosome 1 harbors an eQTL that modulates the expression of Sncg in the mouse retina and identified Pfdn2 as the candidate upstream modulator of Sncg expression. Downregulation of Pfdn2 in enriched RGCs causes a concomitant reduction in Sncg. In this chapter, we describe our strategy and methods for identifying and confirming a genetic modulation of a glaucoma-associated gene. A similar method can be applied to other genes expressed in other tissues.

  19. Putative chemosensory receptors of the codling moth, Cydia pomonella, identified by antennal transcriptome analysis.

    Science.gov (United States)

    Bengtsson, Jonas M; Trona, Federica; Montagné, Nicolas; Anfora, Gianfranco; Ignell, Rickard; Witzgall, Peter; Jacquin-Joly, Emmanuelle

    2012-01-01

    The codling moth, Cydia pomonella, is an important fruit pest worldwide. As nocturnal animals, adults depend to a large extent on olfactory cues for detection of food and mates, and, for females, oviposition sites. In insects, odor detection is mediated by odorant receptors (ORs) and ionotropic receptors (IRs), which ensure the specificity of the olfactory sensory neuron responses. In this study, our aim was to identify chemosensory receptors in the codling moth as a means to uncover new targets for behavioral interference. Using next-generation sequencing techniques, we identified a total of 43 candidate ORs, one gustatory receptor and 15 IRs in the antennal transcriptome. Through Blast and sequence similarity analyses we annotated the insect obligatory co-receptor ORco, five genes clustering in a conserved clade containing sex pheromone receptors, one homolog of the Bombyx mori female-enriched receptor BmorOR30 (but no homologs of the other B. mori female-enriched receptors) and one gene clustering in the sugar receptor family. Among the candidate IRs, we identified homologs of the two highly conserved co-receptors IR8a and IR25a, and one homolog of an IR involved in phenylethyl amine detection in Drosophila. Our results open for functional characterization of the chemosensory receptors of C. pomonella, with potential for new or refined applications of semiochemicals for control of this pest insect.

  20. Putative chemosensory receptors of the codling moth, Cydia pomonella, identified by antennal transcriptome analysis.

    Directory of Open Access Journals (Sweden)

    Jonas M Bengtsson

    Full Text Available The codling moth, Cydia pomonella, is an important fruit pest worldwide. As nocturnal animals, adults depend to a large extent on olfactory cues for detection of food and mates, and, for females, oviposition sites. In insects, odor detection is mediated by odorant receptors (ORs and ionotropic receptors (IRs, which ensure the specificity of the olfactory sensory neuron responses. In this study, our aim was to identify chemosensory receptors in the codling moth as a means to uncover new targets for behavioral interference. Using next-generation sequencing techniques, we identified a total of 43 candidate ORs, one gustatory receptor and 15 IRs in the antennal transcriptome. Through Blast and sequence similarity analyses we annotated the insect obligatory co-receptor ORco, five genes clustering in a conserved clade containing sex pheromone receptors, one homolog of the Bombyx mori female-enriched receptor BmorOR30 (but no homologs of the other B. mori female-enriched receptors and one gene clustering in the sugar receptor family. Among the candidate IRs, we identified homologs of the two highly conserved co-receptors IR8a and IR25a, and one homolog of an IR involved in phenylethyl amine detection in Drosophila. Our results open for functional characterization of the chemosensory receptors of C. pomonella, with potential for new or refined applications of semiochemicals for control of this pest insect.

  1. Proteomic Analysis of Saliva Identifies Potential Biomarkers for Orthodontic Tooth Movement

    Science.gov (United States)

    Ellias, Mohd Faiz; Zainal Ariffin, Shahrul Hisham; Karsani, Saiful Anuar; Abdul Rahman, Mariati; Senafi, Shahidan; Megat Abdul Wahab, Rohaya

    2012-01-01

    Orthodontic treatment has been shown to induce inflammation, followed by bone remodelling in the periodontium. These processes trigger the secretion of various proteins and enzymes into the saliva. This study aims to identify salivary proteins that change in expression during orthodontic tooth movement. These differentially expressed proteins can potentially serve as protein biomarkers for the monitoring of orthodontic treatment and tooth movement. Whole saliva from three healthy female subjects were collected before force application using fixed appliance and at 14 days after 0.014′′ Niti wire was applied. Salivary proteins were resolved using two-dimensional gel electrophoresis (2DE) over a pH range of 3–10, and the resulting proteome profiles were compared. Differentially expressed protein spots were then identified by MALDI-TOF/TOF tandem mass spectrometry. Nine proteins were found to be differentially expressed; however, only eight were identified by MALDI-TOF/TOF. Four of these proteins—Protein S100-A9, immunoglobulin J chain, Ig alpha-1 chain C region, and CRISP-3—have known roles in inflammation and bone resorption. PMID:22919344

  2. A qualitative analysis of aspects of treatment that adolescents with anorexia identify as helpful.

    Science.gov (United States)

    Zaitsoff, Shannon; Pullmer, Rachelle; Menna, Rosanne; Geller, Josie

    2016-04-30

    This study aimed to identify aspects of treatment that adolescents with anorexia nervosa (AN) believe are helpful or unhelpful. Adolescent females receiving treatment for AN or subthreshold AN (n=21) were prompted during semi-structured interviews to generate responses to open-ended questions on what they felt would be most helpful or unhelpful in treating adolescents with eating disorders. Eight codes were developed and the two most frequently endorsed categories were (1) Alliance, where the therapist demonstrates clinical expertise and also expresses interest in the patient (n=21, 100.0%), and (2) Client Involvement in treatment (n=16, 76.2%). These top two categories were shared by participants with AN versus subthreshold AN and participants with high versus low readiness to change their dietary restriction behaviours. Development of the coding scheme and sample participant responses will be discussed. The integration of identified factors into empirically supported treatments for adolescent AN, such as Family-based Treatment, will be considered. This study provides initial information regarding aspects of treatment that adolescents identify as most helpful or unhelpful in their treatment. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Identifying constituents in commercial gasoline using Fourier transform-infrared spectroscopy and independent component analysis.

    Science.gov (United States)

    Pasadakis, Nikos; Kardamakis, Andreas A

    2006-09-25

    A new method is proposed that enables the identification of five refinery fractions present in commercial gasoline mixtures using infrared spectroscopic analysis. The data analysis and interpretation was carried out based on independent component analysis (ICA) and spectral similarity techniques. The FT-IR spectra of the gasoline constituents were determined using the ICA method, exclusively based on the spectra of their mixtures as a blind separation procedure, i.e. assuming unknown the spectra of the constituents. The identity of the constituents was subsequently determined using similarity measures commonly employed in spectra library searches against the spectra of the constituent components. The high correlation scores that were obtained in the identification of the constituents indicates that the developed method can be employed as a rapid and effective tool in quality control, fingerprinting or forensic applications, where gasoline constituents are suspected.

  4. Identifying different types of bulking in an activated sludge system through quantitative image analysis.

    Science.gov (United States)

    Mesquita, D P; Amaral, A L; Ferreira, E C

    2011-10-01

    The present study proposes an image analysis methodology for the identification of different types of disturbances in wastewater treatment activated sludge systems. Up to date, most reported image analysis methodologies have been used in activated sludge processes with the aim of filamentous bulking detection, however, other disturbances could be foreseen in wastewater treatment plants. Such disturbances can lead to fluctuations in the biomass contents, affecting the mixed liquor suspended solids (MLSS), and in the sludge settling ability, affecting the sludge volume index (SVI). Therefore, this work focuses on predicting the MLSS and SVI parameters for different types of disturbances affecting an activated sludge system. Four experiments were conducted simulating filamentous bulking, zoogleal or viscous bulking, pinpoint floc formation, and normal operating conditions. Alongside the MLSS and SVI determination, the aggregated and filamentous biomass contents and morphology were studied as well as the biomass Gram and viability status, by means of image analysis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  5. Meta-analysis of five genome-wide association studies identifies multiple new loci associated with testicular germ cell tumor

    DEFF Research Database (Denmark)

    Wang, Zhaoming; McGlynn, Katherine A.; Rajpert-De Meyts, Ewa

    2017-01-01

    The international Testicular Cancer Consortium (TECAC) combined five published genome-wide association studies of testicular germ cell tumor (TGCT; 3,558 cases and 13,970 controls) to identify new susceptibility loci. We conducted a fixed-effects meta-analysis, including, to our knowledge...... by identifying one and three additional independent SNPs, respectively. In aggregate, the 39 independent markers identified to date explain 37% of father-to-son familial risk, 8% of which can be attributed to the 12 new signals reported here. Our findings substantially increase the number of known TGCT...

  6. Identifying cholera "hotspots" in Uganda: An analysis of cholera surveillance data from 2011 to 2016.

    Science.gov (United States)

    Bwire, Godfrey; Ali, Mohammad; Sack, David A; Nakinsige, Anne; Naigaga, Martha; Debes, Amanda K; Ngwa, Moise C; Brooks, W Abdullah; Garimoi Orach, Christopher

    2017-12-01

    Despite advance in science and technology for prevention, detection and treatment of cholera, this infectious disease remains a major public health problem in many countries in sub-Saharan Africa, Uganda inclusive. The aim of this study was to identify cholera hotspots in Uganda to guide the development of a roadmap for prevention, control and elimination of cholera in the country. We obtained district level confirmed cholera outbreak data from 2011 to 2016 from the Ministry of Health, Uganda. Population and rainfall data were obtained from the Uganda Bureau of Statistics, and water, sanitation and hygiene data from the Ministry of Water and Environment. A spatial scan test was performed to identify the significantly high risk clusters. Cholera hotspots were defined as districts whose center fell within a significantly high risk cluster or where a significantly high risk cluster was completely superimposed onto a district. A zero-inflated negative binomial regression model was employed to identify the district level risk factors for cholera. In total 11,030 cases of cholera were reported during the 6-year period. 37(33%) of 112 districts reported cholera outbreaks in one of the six years, and 20 (18%) districts experienced cholera at least twice in those years. We identified 22 districts as high risk for cholera, of which 13 were near a border of Democratic Republic of Congo (DRC), while 9 districts were near a border of Kenya. The relative risk of having cholera inside the high-risk districts (hotspots) were 2 to 22 times higher than elsewhere in the country. In total, 7 million people were within cholera hotspots. The negative binomial component of the ZINB model shows people living near a lake or the Nile river were at increased risk for cholera (incidence rate ratio, IRR = 0.98, 95% CI: 0.97 to 0.99, p cholera in a district (IRR = 0.99, 95% CI: 0.98 to 1.00, p = .02 and IRR = 1.02, 95% CI: 1.01 to 1.03, p cholera in the district. The study identified cholera

  7. A genome-wide association meta-analysis identifies new childhood obesity loci

    Science.gov (United States)

    Bradfield, Jonathan P.; Taal, H. Rob; Timpson, Nicholas J.; Scherag, André; Lecoeur, Cecile; Warrington, Nicole M.; Hypponen, Elina; Holst, Claus; Valcarcel, Beatriz; Thiering, Elisabeth; Salem, Rany M.; Schumacher, Fredrick R.; Cousminer, Diana L.; Sleiman, Patrick M.A.; Zhao, Jianhua; Berkowitz, Robert I.; Vimaleswaran, Karani S.; Jarick, Ivonne; Pennell, Craig E.; Evans, David M.; St. Pourcain, Beate; Berry, Diane J.; Mook-Kanamori, Dennis O; Hofman, Albert; Rivadeinera, Fernando; Uitterlinden, André G.; van Duijn, Cornelia M.; van der Valk, Ralf J.P.; de Jongste, Johan C.; Postma, Dirkje S.; Boomsma, Dorret I.; Gauderman, William J.; Hassanein, Mohamed T.; Lindgren, Cecilia M.; Mägi, Reedik; Boreham, Colin A.G.; Neville, Charlotte E.; Moreno, Luis A.; Elliott, Paul; Pouta, Anneli; Hartikainen, Anna-Liisa; Li, Mingyao; Raitakari, Olli; Lehtimäki, Terho; Eriksson, Johan G.; Palotie, Aarno; Dallongeville, Jean; Das, Shikta; Deloukas, Panos; McMahon, George; Ring, Susan M.; Kemp, John P.; Buxton, Jessica L.; Blakemore, Alexandra I.F.; Bustamante, Mariona; Guxens, Mònica; Hirschhorn, Joel N.; Gillman, Matthew W.; Kreiner-Møller, Eskil; Bisgaard, Hans; Gilliland, Frank D.; Heinrich, Joachim; Wheeler, Eleanor; Barroso, Inês; O'Rahilly, Stephen; Meirhaeghe, Aline; Sørensen, Thorkild I.A.; Power, Chris; Palmer, Lyle J.; Hinney, Anke; Widen, Elisabeth; Farooqi, I. Sadaf; McCarthy, Mark I.; Froguel, Philippe; Meyre, David; Hebebrand, Johannes; Jarvelin, Marjo-Riitta; Jaddoe, Vincent W.V.; Smith, George Davey; Hakonarson, Hakon; Grant, Struan F.A.

    2012-01-01

    Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made to establish genetic influences on common early-onset obesity. We performed a North American-Australian-European collaborative meta-analysis of fourteen studies consisting of 5,530 cases (≥95th percentile of body mass index (BMI)) and 8,318 controls (childhood obesity cohorts (n = 2,214 cases and 2,674 controls). Finally, these two loci yielded directionally consistent associations in the GIANT meta-analysis of adult BMI1. PMID:22484627

  8. Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians

    DEFF Research Database (Denmark)

    Cho, Yoon Shin; Chen, Chien-Hsiun; Hu, Cheng

    2012-01-01

    We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis...... (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3...

  9. Identifying the Role of National Digital Cadastral Database (ndcdb) in Malaysia and for Land-Based Analysis

    Science.gov (United States)

    Halim, N. Z. A.; Sulaiman, S. A.; Talib, K.; Yusof, O. M.; Wazir, M. A. M.; Adimin, M. K.

    2017-10-01

    This paper explains the process carried out in identifying the significant role of NDCDB in Malaysia specifically in the land-based analysis. The research was initially a part of a larger research exercise to identify the significance of NDCDB from the legal, technical, role and land-based analysis perspectives. The research methodology of applying the Delphi technique is substantially discussed in this paper. A heterogeneous panel of 14 experts was created to determine the importance of NDCDB from the role standpoint. Seven statements pertaining the significant role of NDCDB in Malaysia and land-based analysis were established after three rounds of consensus building. The agreed statements provided a clear definition to describe the important role of NDCDB in Malaysia and for land-based analysis, which was limitedly studied that lead to unclear perception to the general public and even the geospatial community. The connection of the statements with disaster management is discussed concisely at the end of the research.

  10. Analysis of two human parvovirus PARV4 genotypes identified in human plasma for fractionation

    NARCIS (Netherlands)

    Fryer, Jacqueline F.; Delwart, Eric; Bernardin, Flavien; Tuke, Philip W.; Lukashov, Vladimir V.; Baylis, Sally A.

    2007-01-01

    The presence of the novel parvovirus PARV4 and a related variant, PARV5, was recently demonstrated in pooled plasma used in the manufacture of blood and plasma-derived medicinal products. DNA sequence analysis of nearly full-length genomes of four PARV4 and two PARV5 strains from manufacturing

  11. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

    NARCIS (Netherlands)

    M. Cornelis (Marilyn); E.M. Byrne; T. Esko (Tõnu); M.A. Nalls (Michael); A. Ganna (Andrea); N.P. Paynter (Nina); K.L. Monda (Keri); N. Amin (Najaf); K. Fischer (Krista); F. Renström (Frida); J.S. Ngwa; V. Huikari (Ville); A. Cavadino (Alana); I.M. Nolte (Ilja M.); A. Teumer (Alexander); K. Yu; P. Marques-Vidal; R. Rawal; A. Manichaikul (Ani); M.K. Wojczynski (Mary ); J.M. Vink; J.H. Zhao (Jing Hua); G. Burlutsky (George); J. Lahti (Jari); V. Mikkilä (Vera); R.N. Lemaitre (Rozenn ); J. Eriksson; S. Musani (Solomon); T. Tanaka; F. Geller (Frank); J. Luan; J. Hui; R. Mägi (Reedik); M. Dimitriou (Maria); M. Garcia (Melissa); W.-K. Ho; M.J. Wright (Margaret); L.M. Rose (Lynda M.); P.K.E. Magnusson (Patrik K. E.); N.L. Pedersen (Nancy L.); D.J. Couper (David); B.A. Oostra (Ben); A. Hofman (Albert); M.A. Ikram (Arfan); H.W. Tiemeier (Henning); A.G. Uitterlinden (André); F.J.A. van Rooij (Frank); I. Barroso; I. Johansson (Ingegerd); L. Xue (Luting); M. Kaakinen (Marika); L. Milani (Lili); C. Power (Christine); H. Snieder (Harold); R.P. Stolk; S.E. Baumeister (Sebastian); R. Biffar; F. Gu; F. Bastardot (Francois); Z. Kutalik; D.R. Jacobs (David); N.G. Forouhi (Nita G.); E. Mihailov (Evelin); L. Lind (Lars); C. Lindgren; K. Michaëlsson; A.P. Morris (Andrew); M.K. Jensen (Majken K.); K.T. Khaw; R.N. Luben (Robert); J.J. Wang; S. Männistö (Satu); M.-M. Perälä; M. Kähönen (Mika); T. Lehtimäki (Terho); J. Viikari (Jorma); D. Mozaffarian; K. Mukamal (Kenneth); B.M. Psaty (Bruce); A. Döring; A.C. Heath (Andrew C.); G.W. Montgomery (Grant W.); N. Dahmen (N.); T. Carithers; K.L. Tucker; L. Ferrucci (Luigi); H.A. Boyd; M. Melbye (Mads); J.L. Treur; D. Mellström (Dan); J.J. Hottenga (Jouke Jan); I. Prokopenko (Inga); A. Tönjes (Anke); P. Deloukas (Panagiotis); S. Kanoni (Stavroula); M. Lorentzon (Mattias); D.K. Houston; Y. Liu; J. Danesh (John); A. Rasheed; M.A. Mason; A.B. Zonderman; L. Franke (Lude); B.S. Kristal; J. Karjalainen (Juha); D.R. Reed; H.-J. Westra; M.K. Evans; D. Saleheen; T.B. Harris (Tamara); G.V. Dedoussis (George V.); G.C. Curhan (Gary); M. Stumvoll (Michael); J. Beilby (John); L.R. Pasquale; B. Feenstra; S. Bandinelli; J.M. Ordovas; A.T. Chan; U. Peters (Ulrike); C. Ohlsson (Claes); C. Gieger (Christian); N.G. Martin (Nicholas); M. Waldenberger (Melanie); D.S. Siscovick (David); O. Raitakari (Olli); J.G. Eriksson (Johan G.); P. Mitchell (Paul); D. Hunter (David); P. Kraft (Peter); E.B. Rimm (Eric B.); D.I. Boomsma (Dorret); I.B. Borecki (Ingrid); R.J.F. Loos (Ruth); N.J. Wareham (Nick); P.K. Vollenweider (Peter K.); N. Caporaso; H.J. Grabe (Hans Jörgen); M.L. Neuhouser (Marian L.); B.H.R. Wolffenbuttel (Bruce H. R.); F.B. Hu (Frank); E. Hypponen (Elina); M.-R. Jarvelin (Marjo-Riitta); L.A. Cupples (Adrienne); P.W. Franks; P.M. Ridker (Paul); C.M. van Duijn (Cornelia); G. Heiss (Gerardo); A. Metspalu (Andres); K.E. North (Kari); E. Ingelsson (Erik); J.A. Nettleton; R.M. van Dam (Rob); D.I. Chasman (Daniel)

    2015-01-01

    textabstractCoffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day)

  12. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

    NARCIS (Netherlands)

    Cornelis, M. C.; Byrne, E. M.; Esko, T.; Nalls, M. A.; Ganna, A.; Paynter, N.; Monda, K. L.; Amin, N.; Fischer, K.; Renstrom, F.; Ngwa, J. S.; Huikari, V.; Cavadino, A.; Nolte, I. M.; Teumer, A.; Yu, K.; Marques-Vidal, P.; Rawal, R.; Manichaikul, A.; Wojczynski, M. K.; Vink, J. M.; Zhao, J. H.; Burlutsky, G.; Lahti, J.; Mikkila, V.; Lemaitre, R. N.; Eriksson, J.; Musani, S. K.; Tanaka, T.; Geller, F.; Luan, J.; Hui, J.; Maegi, R.; Dimitriou, M.; Garcia, M. E.; Ho, W-K; Wright, M. J.; Rose, L. M.; Magnusson, P. K. E.; Pedersen, N. L.; Couper, D.; Oostra, B. A.; Hofman, A.; Ikram, M. A.; Tiemeier, H. W.; Uitterlinden, A. G.; van Rooij, F. J. A.; Barroso, I.; Johansson, I.; Xue, L.; Kaakinen, M.; Milani, L.; Power, C.; Snieder, H.; Stolk, R. P.; Baumeister, S. E.; Biffar, R.; Gu, F.; Bastardot, F.; Kutalik, Z.; Jacobs, D. R.; Forouhi, N. G.; Mihailov, E.; Lind, L.; Lindgren, C.; Michaelsson, K.; Morris, A.; Jensen, M.; Khaw, K-T; Luben, R. N.; Wang, J. J.; Mannisto, S.; Perala, M-M; Kahonen, M.; Lehtimaki, T.; Viikari, J.; Mozaffarian, D.; Mukamal, K.; Psaty, B. M.; Doering, A.; Heath, A. C.; Montgomery, G. W.; Dahmen, N.; Carithers, T.; Tucker, K. L.; Ferrucci, L.; Boyd, H. A.; Melbye, M.; Treur, J. L.; Mellstrom, D.; Hottenga, J. J.; Prokopenko, I.; Toenjes, A.; Deloukas, P.; Kanoni, S.; Lorentzon, M.; Houston, D. K.; Liu, Y.; Danesh, J.; Rasheed, A.; Mason, M. A.; Zonderman, A. B.; Franke, L.; Kristal, B. S.; Karjalainen, J.; Reed, D. R.; Westra, H-J; Evans, M. K.; Saleheen, D.; Harris, T. B.; Dedoussis, G.; Curhan, G.; Stumvoll, M.; Beilby, J.; Pasquale, L. R.; Feenstra, B.; Bandinelli, S.; Ordovas, J. M.; Chan, A. T.; Peters, U.; Ohlsson, C.; Gieger, C.; Martin, N. G.; Waldenberger, M.; Siscovick, D. S.; Raitakari, O.; Eriksson, J. G.; Mitchell, P.; Hunter, D. J.; Kraft, P.; Rimm, E. B.; Boomsma, D. I.; Borecki, I. B.; Loos, R. J. F.; Wareham, N. J.; Vollenweider, P.; Caporaso, N.; Grabe, H. J.; Neuhouser, M. L.; Wolffenbuttel, B. H. R.; Hu, F. B.; Hyppoenen, E.; Jarvelin, M-R; Cupples, L. A.; Franks, P. W.; Ridker, P. M.; van Duijn, C. M.; Heiss, G.; Metspalu, A.; North, K. E.; Ingelsson, E.; Nettleton, J. A.; van Dam, R. M.; Chasman, D. I.

    Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to

  13. Integrative Genomic Analysis of Cholangiocarcinoma Identifies Distinct IDH-Mutant Molecular Profiles

    DEFF Research Database (Denmark)

    Farshidfar, Farshad; Zheng, Siyuan; Gingras, Marie-Claude

    2017-01-01

    Cholangiocarcinoma (CCA) is an aggressive malignancy of the bile ducts, with poor prognosis and limited treatment options. Here, we describe the integrated analysis of somatic mutations, RNA expression, copy number, and DNA methylation by The Cancer Genome Atlas of a set of predominantly intrahep...

  14. Genome-wide association analysis identifies 13 new risk loci for schizophrenia

    NARCIS (Netherlands)

    Ripke, Stephan; O'Dushlaine, Colm; Chambert, Kimberly; Moran, Jennifer L.; Kähler, Anna K.; Akterin, Susanne; Bergen, Sarah E.; Collins, Ann L.; Crowley, James J.; Fromer, Menachem; Kim, Yunjung; Lee, Sang Hong; Magnusson, Patrik K. E.; Sanchez, Nick; Stahl, Eli A.; Williams, Stephanie; Wray, Naomi R.; Xia, Kai; Bettella, Francesco; Borglum, Anders D.; Bulik-Sullivan, Brendan K.; Cormican, Paul; Craddock, Nick; de Leeuw, Christiaan; Durmishi, Naser; Gill, Michael; Golimbet, Vera; Hamshere, Marian L.; Holmans, Peter; Hougaard, David M.; Kendler, Kenneth S.; Lin, Kuang; Morris, Derek W.; Mors, Ole; Mortensen, Preben B.; Neale, Benjamin M.; O'Neill, Francis A.; Owen, Michael J.; Milovancevic, Milica Pejovic; Posthuma, Danielle; Powell, John; Richards, Alexander L.; Riley, Brien P.; Ruderfer, Douglas; Rujescu, Dan; Sigurdsson, Engilbert; Silagadze, Teimuraz; Smit, August B.; Stefansson, Hreinn; Steinberg, Stacy; Suvisaari, Jaana; Tosato, Sarah; Verhage, Matthijs; Walters, James T.; Levinson, Douglas F.; Gejman, Pablo V.; Laurent, Claudine; Mowry, Bryan J.; O'Donovan, Michael C.; Pulver, Ann E.; Schwab, Sibylle G.; Wildenauer, Dieter B.; Dudbridge, Frank; Shi, Jianxin; Albus, Margot; Alexander, Madeline; Campion, Dominique; Cohen, David; Dikeos, Dimitris; Duan, Jubao; Eichhammer, Peter; Godard, Stephanie; Hansen, Mark; Lerer, F. Bernard; Liang, Kung-Yee; Maier, Wolfgang; Mallet, Jacques; Nertney, Deborah A.; Nestadt, Gerald; Norton, Nadine; Papadimitriou, George N.; Ribble, Robert; Sanders, Alan R.; Silverman, Jeremy M.; Walsh, Dermot; Williams, Nigel M.; Wormley, Brandon; Arranz, Maria J.; Bakker, Steven; Bender, Stephan; Bramon, Elvira; Collier, David; Crespo-Facorro, Benedicto; Hall, Jeremy; Iyegbe, Conrad; Jablensky, Assen; Kahn, Rene S.; Kalaydjieva, Luba; Lawrie, Stephen; Lewis, Cathryn M.; Linszen, Don H.; Mata, Ignacio; McIntosh, Andrew; Murray, Robin M.; Ophoff, Roel A.; van Os, Jim; Walshe, Muriel; Weisbrod, Matthias; Wiersma, Durk; Donnelly, Peter; Barroso, Ines; Blackwell, Jenefer M.; Brown, Matthew A.; Casas, Juan P.; Corvin, Aiden P.; Deloukas, Panos; Duncanson, Audrey; Jankowski, Janusz; Markus, Hugh S.; Mathew, Christopher G.; Palmer, Colin N. A.; Plomin, Robert; Rautanen, Anna; Sawcer, Stephen J.; Trembath, Richard C.; Viswanathan, Ananth C.; Wood, Nicholas W.; Spencer, Chris C. A.; Band, Gavin; Bellenguez, Céline; Freeman, Colin; Hellenthal, Garrett; Giannoulatou, Eleni; Pirinen, Matti; Pearson, Richard D.; Strange, Amy; Su, Zhan; Vukcevic, Damjan; Langford, Cordelia; Hunt, Sarah E.; Edkins, Sarah; Gwilliam, Rhian; Blackburn, Hannah; Bumpstead, Suzannah J.; Dronov, Serge; Gillman, Matthew; Gray, Emma; Hammond, Naomi; Jayakumar, Alagurevathi; McCann, Owen T.; Liddle, Jennifer; Potter, Simon C.; Ravindrarajah, Radhi; Ricketts, Michelle; Tashakkori-Ghanbaria, Avazeh; Waller, Matthew J.; Weston, Paul; Widaa, Sara; Whittaker, Pamela; McCarthy, Mark I.; Stefansson, Kari; Scolnick, Edward; Purcell, Shaun; McCarroll, Steven A.; Sklar, Pamela; Hultman, Christina M.; Sullivan, Patrick F.

    2013-01-01

    Schizophrenia is an idiopathic mental disorder with a heritable component and a substantial public health impact. We conducted a multi-stage genome-wide association study (GWAS) for schizophrenia beginning with a Swedish national sample (5,001 cases and 6,243 controls) followed by meta-analysis with

  15. Students' Self-Identified Long-Term Leadership Development Goals: An Analysis by Gender and Race

    Science.gov (United States)

    Rosch, David M.; Boyd, Barry L.; Duran, Kristina M.

    2014-01-01

    Leadership development goal statements of 92 undergraduate students enrolled in a multi-year self-directed leadership development program were analyzed using content and thematic analyses to investigate patterns of similarities and differences across gender and race. This qualitative analysis utilized a theoretical framework that approached…

  16. Architectural measures of the cancellous bone of the mandibular condyle identified by principal components analysis.

    NARCIS (Netherlands)

    Giesen, E.B.W.; Ding, M.; Dalstra, M.; Eijden, T.M. van

    2003-01-01

    As several morphological parameters of cancellous bone express more or less the same architectural measure, we applied principal components analysis to group these measures and correlated these to the mechanical properties. Cylindrical specimens (n = 24) were obtained in different orientations from

  17. Genome-wide association analysis identifies six new loci associated with forced vital capacity

    NARCIS (Netherlands)

    D.W. Loth (Daan); M.S. Artigas; S.A. Gharib (Sina); L.V. Wain (Louise); N. Franceschini (Nora); B. Koch (Beate); T.D. Pottinger (Tess); G.D. Smith; Q. Duan (Qing); C. Oldmeadow (Christopher); M.K. Lee (Mi Kyeong); D.P. Strachan (David); A.L. James (Alan); J.E. Huffman (Jennifer); V. Vitart (Veronique); A. Ramasamy (Adaikalavan); N.J. Wareham (Nick); J. Kaprio (Jaakko); X.-Q. Wang (Xin-Qun); H. Trochet (Holly); M. Kähönen (Mika); C. Flexeder (Claudia); E. Albrecht (Eva); L.M. Lopez (Lorna); B. Thyagarajan (Bharat); A.C. Alves (Alexessander Couto); S. Enroth (Stefan); E. Omenaas (Ernst); P.K. Joshi (Peter); M. Fall (Magnus); A. Viñuela (Ana); L.J. Launer (Lenore); L.R. Loehr (Laura); M. Fornage (Myriam); G. Li (Guo); J.B. Wilk (Jemma); W. Tang (Wenbo); A. Manichaikul (Ani); L. Lahousse (Lies); T.B. Harris (Tamara); K.E. North (Kari); A.R. Rudnicka (Alicja); J. Hui (Jennie); X. Gu (Xiangjun); T. Lumley (Thomas); A.F. Wright (Alan); N. Hastie (Nick); S. Campbell (Susan); R. Kumar (Rajesh); I. Pin (Isabelle); R.A. Scott (Robert); K.H. Pietilainen (Kirsi Hannele); I. Surakka (Ida); Y. Liu (YongMei); E.G. Holliday (Elizabeth); H. Schulz (Holger); J. Heinrich (Joachim); G. Davies (Gail); J.M. Vonk (Judith); M.K. Wojczynski (Mary ); A. Pouta (Anneli); A. Johansson (Åsa); S.H. Wild (Sarah); E. Ingelsson (Erik); F. Rivadeneira Ramirez (Fernando); H. Völzke (Henry); P.G. Hysi (Pirro); G. Eiriksdottir (Gudny); A.C. Morrison (Alanna); J.I. Rotter (Jerome); W. Gao (Wei); D.S. Postma (Dirkje); W.B. White (Wendy); S.S. Rich (Stephen); A. Hofman (Albert); T. Aspelund (Thor); D. Couper (David); L.J. Smith (Lewis); B.M. Psaty (Bruce); K. Lohman (Kurt); E.G. Burchard (Esteban); A.G. Uitterlinden (André); M. Garcia (Melissa); B.R. Joubert (Bonnie); W.L. McArdle (Wendy); A.W. Musk (Arthur); C.R.W. Hansel (Christian); S.R. Heckbert (Susan); L. Zgaga (Lina); J.B.J. van Meurs (Joyce); P. Navarro (Pau); I. Rudan (Igor); Y.-M. Oh (Yeon-Mok); S. Redline (Susan); D.L. Jarvis (Deborah); J.H. Zhao (Jing Hua); T. Rantanen (Taina); G.T. O'Connor (George); S. Ripatti (Samuli); R.J. Scott (Rodney); S. Karrasch (Stefan); H. Grallert (Harald); N.C. Gaddis (Nathan); J.M. Starr (John); C. Wijmenga (Cisca); R.L. Minster (Ryan); C.W. Lederer (Carsten); J. Pekkanen (Juha); U. Gyllensten (Ulf); H. Campbell (Harry); A.P. Morris (Andrew); S. Gläser (Sven); C.J. Hammond (Christopher); K.M. Burkart (Kristin); J.P. Beilby (John); S.B. Kritchevsky (Stephen); V. Gudnason (Vilmundur); D.B. Hancock (Dana); O.D. Williams (Dale); O. Polasek (Ozren); T. Zemunik (Tatijana); I. Kolcic (Ivana); M.F. Petrini (Marcy); K.T. de Jong (Kim); M. Wjst (Matthias); W.H. Kim (Woo); D.J. Porteous (David J.); G. Scotland (Generation); B.H. Smith (Blair); A. Viljanen (Anne); M. Heliovaara (Markku); J. Attia (John); I. Sayers (Ian); R. Hampel (Regina); C. Gieger (Christian); I.J. Deary (Ian); H.M. Boezen (Marike); A.B. Newman (Anne); M.-R. Jarvelin (Marjo-Riitta); J.F. Wilson (James); L. Lind (Lars); B.H.Ch. Stricker (Bruno); A. Teumer (Alexander); T.D. Spector (Timothy); E. Melén (Erik); M.J. Peters (Marjolein); L.A. Lange (Leslie); R.G. Barr (Graham); K.R. Bracke (Ken); F.M. Verhamme (Fien); J. Sung (Joohon); P.S. Hiemstra (Pieter); P.A. Cassano (Patricia); A. Sood (Akshay); C. Hayward (Caroline); J. Dupuis (Josée); I.P. Hall (Ian); G.G. Brusselle (Guy); M.D. Tobin (Martin); S.J. London (Stephanie)

    2014-01-01

    textabstractForced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in

  18. Genome-wide association analysis identifies six new loci associated with forced vital capacity

    NARCIS (Netherlands)

    Loth, Daan W.; Artigas, Maria Soler; Gharib, Sina A.; Wain, Louise V.; Franceschini, Nora; Koch, Beate; Pottinger, Tess D.; Smith, Albert Vernon; Duan, Qing; Oldmeadow, Chris; Lee, Mi Kyeong; Strachan, David P.; James, Alan L.; Huffman, Jennifer E.; Vitart, Veronique; Ramasamy, Adaikalavan; Wareham, Nicholas J.; Kaprio, Jaakko; Wang, Xin-Qun; Trochet, Holly; Kaonen, Mika; Flexeder, Claudia; Albrecht, Eva; Lopez, Lorna M.; de Jong, Kim; Thyagarajan, Bharat; Alves, Alexessander Couto; Enroth, Stefan; Omenaas, Ernst; Joshi, Peter K.; Fall, Tove; Vinuela, Ana; Launer, Lenore J.; Loehr, Laura R.; Fornage, Myriam; Li, Guo; Wik, Jemma B.; Tang, Wenbo; Manichaikul, Ani; Lahousse, Lies; Harris, Tamara B.; North, Kari E.; Rudnicka, Alicja R.; Hui, Jennie; Gu, Xiangjun; Lumley, Thomas; Wright, Alan F.; Hastie, Nicholas D.; Campbell, Susan; Kumar, Rajesh; Pin, Isabelle; Scott, Robert A.; Pietilainen, Kirsi H.; Surakka, Ida; Liu, Yongmei; Holliday, Elizabeth G.; Schulz, Holger; Heinrich, Joachim; Davies, Gail; Vonk, Judith M.; Wojczynski, Mary; Pouta, Anneli; Johansson, Asa; Wild, Sarah H.; Ingelsson, Erik; Rivadeneira, Fernando; Voezke, Henry; Hysi, Pirro G.; Eiriksdottir, Gudny; Morrison, Alanna C.; Rotter, Jerome I.; Gao, Wei; Postma, Dirkje S.; White, Wendy B.; Rich, Stephen S.; Hofman, Albert; Aspelund, Thor; Couper, David; Smith, Lewis J.; Psaty, Bruce M.; Lohman, Kurt; Burchard, Esteban G.; Uitterlinden, Andre G.; Garcia, Melissa; Joubert, Bonnie R.; McArdle, Wendy L.; Musk, A. Bill; Hansel, Nadia; Heckbert, Susan R.; Zgaga, Lina; van Meurs, Joyce B. J.; Navarro, Pau; Rudan, Igor; Oh, Yeon-Mok; Redline, Susan; Jarvis, Deborah L.; Rantanen, Taina; O'Connor, George T.; Ripatti, Samuli; Scott, Rodney J.; Karrasch, Stefan; Grallert, Harald; Gaddis, Nathan C.; Starr, John M.; Wijmenga, Cisca; Minster, Ryan L.; Lederer, David J.; Pekkanen, Juha; Gyllensten, Ulf; Campbe, Harry; Morris, Andrew P.; Glaeser, Sven; Hammond, Christopher J.; Burkart, Kristin M.; Beilby, John; Kritchevsky, Stephen B.; Gucinason, Vilrnundur; Hancock, Dana B.; Williams, Dale; Polasek, Ozren; Zemunik, Tatijana; Kolcic, Ivana; Petrini, Marcy F.; Wjst, Matthias; Kim, Woo Jin; Porteous, David J.; Scotland, Generation; Smith, Blair H.; Villanen, Anne; Heliovaara, Markku; Attia, John R.; Sayers, Ian; Hampel, Regina; Gieger, Christian; Deary, Ian J.; Boezen, Hendrika; Newman, Anne; Jarvelin, Marjo-Riitta; Wilson, James F.; Lind, Lars; Stricker, Bruno H.; Teumer, Alexander; Spector, Timothy D.; Melen, Erik; Peters, Marjolein J.; Lange, Leslie A.; Barr, R. Graham; Bracke, Ken R.; Verhamme, Fien M.; Sung, Joohon; Hiemstra, Pieter S.; Cassano, Patricia A.; Sood, Akshay; Hayward, Caroline; Dupuis, Josee; Hall, Ian P.; Brusselle, Guy G.; Tobin, Martin D.; London, Stephanie J.

    Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917

  19. A patent landscape analysis for organic photovoltaic solar cells: Identifying the technology's development phase

    NARCIS (Netherlands)

    Lizin, Sebastien; Leroy, Julie; Delvenne, Catherine; Dijk, Marc; De Schepper, Ellen; Van Passel, Steven

    2013-01-01

    Organic photovoltaics (OPV) have developed into a vast research area. Progress in various directions has made it difficult to monitor the technology's precise development state. We offer a patent landscape analysis over all OPV devices, their substrates and encapsulation materials to provide an

  20. Genome-wide meta-analysis identifies new susceptibility loci for migraine

    DEFF Research Database (Denmark)

    Anttila, Verneri; Winsvold, Bendik S; Gormley, Padhraig

    2013-01-01

    Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases...

  1. Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption

    NARCIS (Netherlands)

    Cornelis, M. C.; Byrne, E. M.; Esko, T.; Nalls, M. A.; Ganna, A.; Paynter, N.; Monda, K. L.; Amin, N.; Fischer, K.; Renstrom, F.; Ngwa, J. S.; Huikari, V.; Cavadino, A.; Nolte, I. M.; Teumer, A.; Yu, K.; Marques-Vidal, P.; Rawal, R.; Manichaikul, A.; Wojczynski, M. K.; Vink, J. M.; Zhao, J. H.; Burlutsky, G.; Lahti, J.; Mikkilä, V.; Lemaitre, R. N.; Eriksson, J.; Musani, S. K.; Tanaka, T.; Geller, F.; Luan, J.; Hui, J.; Mägi, R.; Dimitriou, M.; Garcia, M. E.; Ho, W.-K.; Wright, M. J.; Rose, L. M.; Magnusson, P. K. E.; Pedersen, N. L.; Couper, D.; Oostra, B. A.; Hofman, A.; Ikram, M. A.; Tiemeier, H. W.; Uitterlinden, A. G.; van Rooij, F. J. A.; Barroso, I.; Johansson, I.; Xue, L.; Kaakinen, M.; Milani, L.; Power, C.; Snieder, H.; Stolk, R. P.; Baumeister, S. E.; Biffar, R.; Gu, F.; Bastardot, F.; Kutalik, Z.; Jacobs, D. R.; Forouhi, N. G.; Mihailov, E.; Lind, L.; Lindgren, C.; Michaëlsson, K.; Morris, A.; Jensen, M.; Khaw, K.-T.; Luben, R. N.; Wang, J. J.; Männistö, S.; Perälä, M.-M.; Kähönen, M.; Lehtimäki, T.; Viikari, J.; Mozaffarian, D.; Mukamal, K.; Psaty, B. M.; Döring, A.; Heath, A. C.; Montgomery, G. W.; Dahmen, N.; Carithers, T.; Tucker, K. L.; Ferrucci, L.; Boyd, H. A.; Melbye, M.; Treur, J. L.; Mellström, D.; Hottenga, J. J.; Prokopenko, I.; Tönjes, A.; Deloukas, P.; Kanoni, S.; Lorentzon, M.; Houston, D. K.; Liu, Y.; Danesh, J.; Rasheed, A.; Mason, M. A.; Zonderman, A. B.; Franke, L.; Kristal, B. S.; Karjalainen, J.; Reed, D. R.; Westra, H.-J.; Evans, M. K.; Saleheen, D.; Harris, T. B.; Dedoussis, G.; Curhan, G.; Stumvoll, M.; Beilby, J.; Pasquale, L. R.; Feenstra, B.; Bandinelli, S.; Ordovas, J. M.; Chan, A. T.; Peters, U.; Ohlsson, C.; Gieger, C.; Martin, N. G.; Waldenberger, M.; Siscovick, D. S.; Raitakari, O.; Eriksson, J. G.; Mitchell, P.; Hunter, D. J.; Kraft, P.; Rimm, E. B.; Boomsma, D. I.; Borecki, I. B.; Loos, R. J. F.; Wareham, N. J.; Vollenweider, P.; Caporaso, N.; Grabe, H. J.; Neuhouser, M. L.; Wolffenbuttel, B. H. R.; Hu, F. B.; Hyppönen, E.; Järvelin, M.-R.; Cupples, L. A.; Franks, P. W.; Ridker, P. M.; van Duijn, C. M.; Heiss, G.; Metspalu, A.; North, K. E.; Ingelsson, E.; Nettleton, J. A.; van Dam, R. M.; Chasman, D. I.; Nalls, Michael A.; Plagnol, Vincent; Hernandez, Dena G.; Sharma, Manu; Sheerin, Una-Marie; Saad, Mohamad; Simón-Sánchez, Javier; Schulte, Claudia; Lesage, Suzanne; Sveinbjörnsdóttir, Sigurlaug; Arepalli, Sampath; Barker, Roger; Ben-Shlomo, Yoav; Berendse, Henk W.; Berg, Daniela; Bhatia, Kailash; de Bie, Rob M. A.; Biffi, Alessandro; Bloem, Bas; Bochdanovits, Zoltan; Bonin, Michael; Bras, M.; Brockmann, Kathrin; Brooks, Janet; Burn, David J.; Charlesworth, Gavin; Chen, Honglei; Chinnery, Patrick F.; Chong, Sean; Clarke, Carl E.; Cookson, Mark R.; Cooper, J. Mark; Corvol, Jean Christophe; Counsell, Carl; Damier, Philippe; Dartigues, Jean-François; Deloukas, Panos; Deuschl, Günther; Dexter, David T.; van Dijk, Karin D.; Dillman, Allissa; Durif, Frank; Dürr, Alexandra; Edkins, Sarah; Evans, Jonathan R.; Foltynie, Thomas; Dong, Jing; Gardner, Michelle; Gibbs, J. Raphael; Goate, Alison; Gray, Emma; Guerreiro, Rita; Harris, Clare; van Hilten, Jacobus J.; Hofman, Albert; Hollenbeck, Albert; Holton, Janice; Hu, Michele; Huang, Xuemei; Hershey, Milton S.; Wurster, Isabel; Mätzler, Walter; Hudson, Gavin; Hunt, Sarah E.; Huttenlocher, Johanna; Illig, Thomas; München, Helmholtz Zentrum; Jónsson, Pálmi V.; Lambert, Jean-Charles; Langford, Cordelia; Lees, Andrew; Lichtner, Peter; Limousin, Patricia; Lopez, Grisel; Lorenz, Delia; McNeill, Alisdair; Moorby, Catriona; Moore, Matthew; Morris, Huw R.; Morrison, Karen E.; O' Sullivan, Sean S.; Pearson, Justin; Perlmutter, Joel S.; Pétursson, Hjörvar; Pollak, Pierre; Potter, Simon; Ravina, Bernard; Revesz, Tamas; Riess, Olaf; Rivadeneira, Fernando; Rizzu, Patrizia; Ryten, Mina; Sawcer, Stephen; Schapira, Anthony; Scheffer, Hans; Shaw, Karen; Sidransky, Ellen; Smith, Colin; Spencer, Chris C. A.; Stefánsson, Hreinn; Bettella, Francesco; Stockton, Joanna D.; Strange, Amy; Talbot, Kevin; Tanner, M.; Tashakkori-Ghanbaria, Avazeh; Tison, François; Trabzuni, Daniah; Traynor, Bryan J.; Uitterlinden, André G.; Velseboer, Daan; Vidailhet, Marie; Walker, Robert; van de Warrenburg, Bart; Wickremaratchi, Mirdhu; Williams, Nigel; Williams-Gray, Caroline H.; Winder-Rhodes, Sophie; Stefánsson, Kári; Martinez, Maria; Sabatier, Paul; Wood, Nicholas W.; Hardy, John; Heutink, Peter; Brice, Alexis; Gasser, Thomas; Singleton, Andrew B.; Singleton, Andrew; Cookson, Mark; Hernandez, Dena; Nalls, Michael; Zonderman, Alan; Ferrucci, Luigi; Johnson, Robert; Longo, Dan; O'Brien, Richard; Traynor, Bryan; Troncoso, Juan; van der Brug, Marcel; Zielke, Ronald; Weale, Michael; Ramasamy, Adaikalavan; Box, P. O.

    2015-01-01

    Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to

  2. A situation awareness analysis scheme to identify deficiencies of complex man-machine interactions

    NARCIS (Netherlands)

    van Doorn, E.C.; Rusak, Z.; Horvath, I.

    2017-01-01

    This paper presents an analysis scheme which aims to support a
    systematic study of required situation awareness (RSA). This scheme supports
    identification of deficiencies of support for situation awareness (SA).
    Information needs are goal and task dependent and can be defined

  3. Social Learning Network Analysis Model to Identify Learning Patterns Using Ontology Clustering Techniques and Meaningful Learning

    Science.gov (United States)

    Firdausiah Mansur, Andi Besse; Yusof, Norazah

    2013-01-01

    Clustering on Social Learning Network still not explored widely, especially when the network focuses on e-learning system. Any conventional methods are not really suitable for the e-learning data. SNA requires content analysis, which involves human intervention and need to be carried out manually. Some of the previous clustering techniques need…

  4. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

    NARCIS (Netherlands)

    Felix, Janine F.; Bradfield, Jonathan P.; Monnereau, Claire; van der Valk, Ralf J. P.; Stergiakouli, Evie; Chesi, Alessandra; Gaillard, Romy; Feenstra, Bjarke; Thiering, Elisabeth; Kreiner-Moller, Eskil; Mahajan, Anubha; Pitkanen, Niina; Joro, Raimo; Cavadino, Alana; Huikari, Ville; Franks, Steve; Groen-Blokhuis, Maria M.; Cousminer, Diana L.; Marsh, Julie A.; Lehtimaki, Terho; Curtin, John A.; Vioque, Jesus; Ahluwalia, Tarunveer S.; Myhre, Ronny; Price, Thomas S.; Vilor-Tejedor, Natalia; Yengo, Loic; Grarup, Niels; Ntalla, Ioanna; Ang, Wei; Atalay, Mustafa; Bisgaard, Hans; Blakemore, Alexandra I.; Bonnefond, Amelie; Carstensen, Lisbeth; Eriksson, Johan; Flexeder, Claudia; Franke, Lude; Geller, Frank; Geserick, Mandy; Hartikainen, Anna-Liisa; Haworth, Claire M. A.; Hirschhorn, Joel N.; Hofman, Albert; Holm, Jens-Christian; Horikoshi, Momoko; Hottenga, Jouke Jan; Huang, Jinyan; Kadarmideen, Haja N.; Kahonen, Mika; Kiess, Wieland; Lakka, Hanna-Maaria; Lakka, Timo A.; Lewin, Alexandra M.; Liang, Liming; Lyytikainen, Leo-Pekka; Ma, Baoshan; Magnus, Per; McCormack, Shana E.; McMahon, George; Mentch, Frank D.; Middeldorp, Christel M.; Murray, Clare S.; Pahkala, Katja; Pers, Tune H.; Pfaefle, Roland; Postma, Dirkje S.; Power, Christine; Simpson, Angela; Sengpiel, Verena; Tiesler, Carla M. T.; Torrent, Maties; Uitterlinden, Andre G.; van Meurs, Joyce B.; Vinding, Rebecca; Waage, Johannes; Wardle, Jane; Zeggini, Eleftheria; Zemel, Babette S.; Dedoussis, George V.; Pedersen, Oluf; Froguel, Philippe; Sunyer, Jordi; Plomin, Robert; Jacobsson, Bo; Hansen, Torben; Gonzalez, Juan R.; Custovic, Adnan; Raitakari, Olli T.; Pennell, Craig E.; Widen, Elisabeth; Boomsma, Dorret I.; Koppelman, Gerard H.; Sebert, Sylvain; Jarvelin, Marjo-Riitta; Hypponen, Elina; McCarthy, Mark I.; Lindi, Virpi; Harri, Niinikoski; Koerner, Antje; Bonnelykke, Klaus; Heinrich, Joachim; Melbye, Mads; Rivadeneira, Fernando; Hakonarson, Hakon; Ring, Susan M.; Smith, George Davey; Sorensen, Thorkild I. A.; Timpson, Nicholas J.; Grant, Struan F. A.; Jaddoe, Vincent W. V.

    2016-01-01

    A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex-and age-adjusted standard deviation scores. We

  5. Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index

    NARCIS (Netherlands)

    J.F. Felix (Janine); J.P. Bradfield (Jonathan); C. Monnereau; R.J.P. van der Valk (Ralf); E. Stergiakouli (Evie); A. Chesi (Alessandra); R. Gaillard (Romy); B. Feenstra (Bjarke); E. Thiering (Elisabeth); E. Kreiner-Møller (Eskil); A. Mahajan (Anubha); Niina Pitkänen; R. Joro (Raimo); A. Cavadino (Alana); V. Huikari (Ville); S. Franks (Steve); M. Groen-Blokhuis (Maria); D.L. Cousminer (Diana); J.A. Marsh (Julie); T. Lehtimäki (Terho); J.A. Curtin (John); J. Vioque (Jesus); T.S. Ahluwalia (Tarunveer Singh); R. Myhre (Ronny); T.S. Price (Thomas); Natalia Vilor-Tejedor; L. Yengo (Loic); N. Grarup (Niels); I. Ntalla (Ioanna); W.Q. Ang (Wei); M. Atalay (Mustafa); H. Bisgaard (Hans); A.I.F. Blakemore (Alexandra); A. Bonnefond (Amélie); L. Carstensen (Lisbeth); J.G. Eriksson (Johan G.); C. Flexeder (Claudia); L. Franke (Lude); F. Geller (Frank); M. Geserick (Mandy); A.L. Hartikainen; C.M.A. Haworth (Claire M.); J.N. Hirschhorn (Joel N.); A. Hofman (Albert); J.-C. Holm (Jens-Christian); M. Horikoshi (Momoko); J.J. Hottenga (Jouke Jan); J. Huang (Jian); H.N. Kadarmideen (Haja N.); M. Kähönen (Mika); W. Kiess (Wieland); T.A. Lakka (Timo); T.A. Lakka (Timo); A. Lewin (Alex); L. Liang (Liming); L.-P. Lyytikäinen (Leo-Pekka); B. Ma (Baoshan); P. Magnus (Per); S.E. McCormack (Shana E.); G. Mcmahon (George); F.D. Mentch (Frank); C.M. Middeldorp (Christel); C.S. Murray (Clare S.); K. Pahkala (Katja); T.H. Pers (Tune); R. Pfäffle (Roland); D.S. Postma (Dirkje); C. Power (Christine); A. Simpson (Angela); V. Sengpiel (Verena); C. Tiesler (Carla); M. Torrent (Maties); A.G. Uitterlinden (André); J.B.J. van Meurs (Joyce); R. Vinding (Rebecca); J. Waage (Johannes); J. Wardle (Jane); E. Zeggini (Eleftheria); B.S. Zemel (Babette S.); G.V. Dedoussis (George); O. Pedersen (Oluf); P. Froguel (Philippe); J. Sunyer (Jordi); R. Plomin (Robert); B. Jacobsson (Bo); T. Hansen (Torben); J.R. Gonzalez (Juan R.); A. Custovic; O.T. Raitakari (Olli T.); C.E. Pennell (Craig); Elisabeth Widén; D.I. Boomsma (Dorret); G.H. Koppelman (Gerard); S. Sebert (Sylvain); M.-R. Jarvelin (Marjo-Riitta); E. Hypponen (Elina); M.I. McCarthy (Mark); V. Lindi (Virpi); N. Harri (Niinikoski); A. Körner (Antje); K. Bønnelykke (Klaus); J. Heinrich (Joachim); M. Melbye (Mads); F. Rivadeneira Ramirez (Fernando); H. Hakonarson (Hakon); S.M. Ring (Susan); G.D. Smith; T.I.A. Sørensen (Thorkild I.A.); N.J. Timpson (Nicholas); S.F.A. Grant (Struan); V.W.V. Jaddoe (Vincent); H.J. Kalkwarf (Heidi J.); J.M. Lappe (Joan M.); V. Gilsanz (Vicente); S.E. Oberfield (Sharon E.); J.A. Shepherd (John A.); A. Kelly (Andrea)

    2016-01-01

    textabstractA large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown.We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation

  6. Quantitative assessment of in-solution digestion efficiency identifies optimal protocols for unbiased protein analysis

    DEFF Research Database (Denmark)

    Leon, Ileana R; Schwämmle, Veit; Jensen, Ole N

    2013-01-01

    conditions (buffer, RapiGest, deoxycholate, urea), and two methods for removal of detergents prior to analysis of peptides (acid precipitation or phase separation with ethyl acetate). Our data-independent quantitative LC-MS/MS workflow quantified over 3700 distinct peptides with 96% completeness between all...

  7. Short communication: Practical issues in implementing volatile metabolite analysis for identifying mastitis pathogens.

    Science.gov (United States)

    Hettinga, Kasper A; de Bok, Frank A M; Lam, Theo J G M

    2015-11-01

    Several parameters for improving volatile metabolite analysis using headspace gas chromatography-mass spectrometry (GC-MS) analysis of volatile metabolites were evaluated in the framework of identification of mastitis-causing pathogens. Previous research showed that the results of such volatile metabolites analysis were comparable with those based on bacteriological culturing. The aim of this study was to evaluate the effect of several method changes on the applicability and potential implementation of this method in practice. The use of a relatively polar column is advantageous, resulting in a faster and less complex chromatographic setup with a higher resolving power yielding higher-quality data. Before volatile metabolite analysis is applied, a minimum incubation of 8h is advised, as reducing incubation time leads to less reliable pathogen identification. Application of GC-MS remained favorable compared with regular gas chromatography. The complexity and cost of a GC-MS system are such that this limits the application of the method in practice for identification of mastitis-causing pathogens. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  8. Identifying Loblolly Pine and Four Common Competing Hardwood Species Using MultiSpectral Reflectance Analysis

    Science.gov (United States)

    T.C. Knight; A.W. Ezell; D.R. Shaw; J.D. Byrd; D.L. Evans

    2004-01-01

    Multispectral reflectance data were collected in midrotation loblolly pine plantations during spring, summer, and fall seasons with a hand-held spectroradiometer. All data were analyzed by discriminant analysis. Analyses resulted in species classifications with accuracies of 83 percent during the spring season, 54 percent during summer, and 82 percent during fall....

  9. A genome-wide association meta-analysis identifies new childhood obesity loci

    NARCIS (Netherlands)

    Bradfield, Jonathan P.; Taal, H. Rob; Timpson, Nicholas J.; Scherag, Andre; Lecoeur, Cecile; Warrington, Nicole M.; Hypponen, Elina; Holst, Claus; Valcarcel, Beatriz; Thiering, Elisabeth; Salem, Rany M.; Schumacher, Fredrick R.; Cousminer, Diana L.; Sleiman, Patrick M. A.; Zhao, Jianhua; Berkowitz, Robert I.; Vimaleswaran, Karani S.; Jarick, Ivonne; Pennell, Craig E.; Evans, David M.; St Pourcain, Beate; Berry, Diane J.; Mook-Kanamori, Dennis O.; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G.; van Duijn, Cornelia M.; van der Valk, Ralf J. P.; de Jongste, Johan C.; Postma, Dirkje S.; Boomsma, Dorret I.; Gauderman, W. James; Hassanein, Mohamed T.; Lindgren, Cecilia M.; Magi, Reedik; Boreham, Colin A. G.; Neville, Charlotte E.; Moreno, Luis A.; Elliott, Paul; Pouta, Anneli; Hartikainen, Anna-Liisa; Li, Mingyao; Raitakari, Olli; Lehtimaki, Terho; Eriksson, Johan G.; Palotie, Aarno; Dallongeville, Jean; Das, Shikta; Deloukas, Panos; McMahon, George; Ring, Susan M.; Kemp, John P.; Buxton, Jessica L.; Blakemore, Alexandra I. F.; Bustamante, Mariona; Guxens, Monica; Hirschhorn, Joel N.; Gillman, Matthew W.; Kreiner-Moller, Eskil; Bisgaard, Hans; Gilliland, Frank D.; Heinrich, Joachim; Wheeler, Eleanor; Barroso, Ines; O'Rahilly, Stephen; Meirhaeghe, Aline; Sorensen, Thorkild I. A.; Power, Chris; Palmer, Lyle J.; Hinney, Anke; Widen, Elisabeth; Farooqi, I. Sadaf; McCarthy, Mark I.; Froguel, Philippe; Meyre, David; Hebebrand, Johannes; Jarvelin, Marjo-Riitta; Jaddoe, Vincent W. V.; Smith, George Davey; Hakonarson, Hakon; Grant, Struan F. A.

    Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of

  10. A genome-wide association meta-analysis identifies new childhood obesity loci

    NARCIS (Netherlands)

    Bradfield, J.P.; Taal, H.R.; Timpson, N.J.; Scherag, A.; Lecoeur, C.; Warrington, N.M.; Hypponen, E.; Holst, C.; Valcarcel, B.; Thiering, E.; Salem, R.M.; Schumacher, F.R.; Cousminer, D.L.; Sleiman, P.M.A.; Zhao, J.; Berkowitz, R.I.; Vimaleswaran, K.S.; Jarick, I.; Pennell, C.E.; Evans, D.M.; St Pourcain, B.; Berry, D.J.; Mook-Kanamori, D.O.; Hofman, A.; Rivadeneira, F.; Uitterlinden, A.G.; van Duijn, C.M.; van der Valk, R.J.P.; de Jongste, J.C.; Postma, D.S.; Boomsma, D.I.; Gauderman, W.J.; Hassanein, M.T.; Lindgren, C.M.; Mägi, R.; Boreham, C.A.G.; Neville, C.E.; Moreno, L.A.; Elliott, P.; Pouta, A.; Hartikainen, A.-L.; Li, M.; Raitakari, O.; Lehtimäki, T.; Eriksson, J.G.; Palotie, A.; Dallongeville, J.; Das, S.; Deloukas, P.; McMahon, G.; Ring, S.M.; Kemp, J.P.; Buxton, J.L.; Blakemore, A.I.F.; Bustamante, M.; Guxens, M.; Hirschhorn, J.N.; Gillman, M.W.; Kreiner-Møller, E.; Bisgaard, H.; Gilliland, F.D.; Heinrich, J.; Wheeler, E.; Barroso, I.; O'Rahilly, S.; Meirhaeghe, A.; Sørensen, T.I.A.; Power, C.; Palmer, L.J.; Hinney, A.; Widen, E.; Farooqi, I.S.; McCarthy, M.I.; Froguel, P.; Meyre, D.; Hebebrand, J.; Järvelin, M.J.; Jaddoe, V.W.V.; Smith, G.D.; Hakonarson, H.; Grant, S.F.A.

    2012-01-01

    Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of

  11. Large-scale gene-centric analysis identifies novel variants for coronary artery disease

    NARCIS (Netherlands)

    Butterworth, A.S.; Braund, P.S.; Hardwick, R.J.; Saleheen, D.; Peden, J.F.; Soranzo, N.; Chambers, J.C.; Kleber, M.E.; Keating, B.; Qasim, A.; Klopp, N.; Erdmann, J.; Basart, H.; Baumert, J.H.; Bezzina, C.R.; Boehm, B.O.; Brocheton, J.; Bugert, P.; Cambien, F.; Collins, R.; Couper, D.; Jong, J.S. de; Diemert, P.; Ejebe, K.; Elbers, C.C.; Elliott, P.; Fornage, M.; Frossard, P.; Garner, S.; Hunt, S.E.; Kastelein, J.J.; Klungel, O.H.; Kluter, H.; Koch, K.; Konig, I.R.; Kooner, A.S.; Liu, K.; McPherson, R.; Musameh, M.D.; Musani, S.; Papanicolaou, G.; Peters, A.; Peters, B.J.; Potter, S.; Psaty, B.M.; Rasheed, A.; Scott, J.; Seedorf, U.; Sehmi, J.S.; Sotoodehnia, N.; Stark, K.; Stephens, J.; Schoot, C.E. van der; Schouw, Y.T. van der; Harst, P. van der; Vasan, R.S.; Wilde, A.A.; Willenborg, C.; Winkelmann, B.R.; Zaidi, M.; Zhang, W.; Ziegler, A.; Koenig, W.; Matz, W.; Trip, M.D.; Reilly, M.P.; Kathiresan, S.; Schunkert, H.; Hamsten, A.; Hall, A.S.; Kooner, J.S.; Thompson, S.G.; Thompson, J.R.; Watkins, H.; Danesh, J.; Barnes, T.; Rafelt, S.; Codd, V.; Bruinsma, N.; Dekker, L.R.; Henriques, J.P.; Koch, K.T.; Winter, R.J. de; Alings, M.; Allaart, C.F.; Gorgels, A.P.; Verheugt, F.W.A.; Mueller, M.; Meisinger, C.; DerOhannessian, S.; Mehta, N.N.; Ferguson, J.; Hakonarson, H.; Matthai, W.; Wilensky, R.; Hopewell, J.C.; Parish, S.; Linksted, P.; Notman, J.; Gonzalez, H.; Young, A.; Ostley, T.; Munday, A.; Goodwin, N.; Verdon, V.; Shah, S.; Edwards, C.; Mathews, C.; Gunter, R.; Benham, J.; Davies, C.; Cobb, M.; Cobb, L.; Crowther, J.; Richards, A.; Silver, M.; Tochlin, S.; Mozley, S.; Clark, S.; Radley, M.; Kourellias, K.; Olsson, P.; Barlera, S.; Tognoni, G.; Rust, S.; Assmann, G.; Heath, S.; Zelenika, D.; Gut, I.; Green, F.; Farrall, M.; Goel, A.; Ongen, H.; Franzosi, M.G.; Lathrop, M.; Clarke, R.; Aly, A.; Anner, K.; Bjorklund, K.; Blomgren, G.; Cederschiold, B.; Danell-Toverud, K.; Eriksson, P.; Grundstedt, U.; Heinonen, M.; Hellenius, M.L.; Hooft, F. van 't; Husman, K.; Lagercrantz, J.; Larsson, A.; Larsson, M.; Mossfeldt, M.; Malarstig, A.; Olsson, G.; Sabater-Lleal, M.; Sennblad, B.; Silveira, A.; Strawbridge, R.; Soderholm, B.; Ohrvik, J.; Zaman, K.S.; Mallick, N.H.; Azhar, M.; Samad, A.; Ishaq, M.; Shah, N.; Samuel, M.; Kathiresan, S.C.; Assimes, T.L.; Holm, H.; Preuss, M.; Stewart, A.F.; Barbalic, M.; Gieger, C.; Absher, D.; Aherrahrou, Z.; Allayee, H.; Altshuler, D.; Anand, S.; Andersen, K.; Anderson, J.L.; Ardissino, D.; Ball, S.G.; Balmforth, A.J.; Barnes, T.A.; Becker, L.C.; Becker, D.M.; Berger, K.; Bis, J.C.; Boekholdt, S.M.; Boerwinkle, E.; Brown, M.J.; Burnett, M.S.; Buysschaert, I.; Carlquist, J.F.; Chen, L.; Davies, R.W.; Dedoussis, G.; Dehghan, A.; Demissie, S.; Devaney, J.; Do, R.; Doering, A.; El Mokhtari, N.E.; Ellis, S.G.; Elosua, R.; Engert, J.C.; Epstein, S.; Faire, U. de; Fischer, M.; Folsom, A.R.; Freyer, J.; Gigante, B.; Girelli, D.; Gretarsdottir, S.; Gudnason, V.; Gulcher, J.R.; Tennstedt, S.; Halperin, E.; Hammond, N.; Hazen, S.L.; Hofman, A.; Horne, B.D.; Illig, T.; Iribarren, C.; Jones, G.T.; Jukema, J.W.; Kaiser, M.A.; Kaplan, L.M.; Khaw, K.T.; Knowles, J.W.; Kolovou, G.; Kong, A.; Laaksonen, R.; Lambrechts, D.; Leander, K.; Li, M.; Lieb, W.; Lettre, G.; Loley, C.; Lotery, A.J.; Mannucci, P.M.; Martinelli, N.; McKeown, P.P.; Meitinger, T.; Melander, O.; Merlini, P.A.; Mooser, V.; Morgan, T.; Muhleisen T.W., .; Muhlestein, J.B.; Musunuru, K.; Nahrstaedt, J.; Nothen, Markus; Olivieri, O.; Peyvandi, F.; Patel, R.S.; Patterson, C.C.; Qu, L.; Quyyumi, A.A.; Rader, D.J.; Rallidis, L.S.; Rice, C.; Roosendaal, F.R.; Rubin, D.; Salomaa, V.; Sampietro, M.L.; Sandhu, M.S.; Schadt, E.; Schafer, A.; Schillert, A.; Schreiber, S.; Schrezenmeir, J.; Schwartz, S.M.; Siscovick, D.S.; Sivananthan, M.; Sivapalaratnam, S.; Smith, A.V.; Smith, T.B.; Snoep, J.D.; Spertus, J.A.; Stefansson, K.; Stirrups, K.; Stoll, M.; Tang, W.H.; Thorgeirsson, G.; Thorleifsson, G.; Tomaszewski, M.; Uitterlinden, A.G.; Rij, A.M. van; Voight, B.F.; Wareham, N.J.; AWells, G.; Wichmann, H.E.; Witteman, J.C.; Wright, B.J.; Ye, S.; Cupples, L.A.; Quertermous, T.; Marz, W.; Blankenberg, S.; Thorsteinsdottir, U.; Roberts, R.; O'Donnell, C.J.; Onland-Moret, N.C.; Setten, J. van; Bakker, P.I. de; Verschuren, W.M.; Boer, J.M.; Wijmenga, C.; Hofker, M.H.; Maitland-van der Zee, A.H.; Boer, A. de; Grobbee, D.E.; Attwood, T.; Belz, S.; Cooper, J.; Crisp-Hihn, A.; Deloukas, P.; Foad, N.; Goodall, A.H.; Gracey, J.; Gray, E.; Gwilliams, R.; Heimerl, S.; Hengstenberg, C.; Jolley, J.; Krishnan, U.; Lloyd-Jones, H.; Lugauer, I.; Lundmark, P.; Maouche, S.; Moore, J.S.; Muir, D.; Murray, E.; Nelson, C.P.; Neudert, J.; Niblett, D.; O'Leary, K.; Ouwehand, W.H.; Pollard, H.; Rankin, A.; Rice, C.M.; Sager, H.; Samani, N.J.; Sambrook, J.; Schmitz, G.; Scholz, M.; Schroeder, L.; Syvannen, A.C.; Wallace, C.

    2011-01-01

    Coronary artery disease (CAD) has a significant genetic contribution that is incompletely characterized. To complement genome-wide association (GWA) studies, we conducted a large and systematic candidate gene study of CAD susceptibility, including analysis of many uncommon and functional variants.

  12. Identifying blue whiting (Micromesistius poutassou) stock structure in the Northeast Atlantic by otolith shape analysis

    DEFF Research Database (Denmark)

    Mahe, Kélig; Oudard, Clémence; Mille, Tiphaine

    2016-01-01

    Information on stock identification and spatial stock structure provide a basis for understanding fish population dynamics and improving fisheries management. In this study, otolith shape analysis was used to study the stock structure of blue whiting (Micromesistius poutassou) in the northeast At...