Integrative EEG biomarkers predict progression to Alzheimer's disease at the MCI stage

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Simon-Shlomo ePoil

2013-10-01

Full Text Available Alzheimer's disease (AD is a devastating disorder of increasing prevalence in modern society. Mild cognitive impairment (MCI is considered a transitional stage between normal aging and AD; however, not all subjects with MCI progress to AD. Prediction of conversion to AD at an early stage would enable an earlier, and potentially more effective, treatment of AD. Electroencephalography (EEG biomarkers would provide a non-invasive and relatively cheap screening tool to predict conversion to AD; however, traditional EEG biomarkers have not been considered accurate enough to be useful in clinical practice. Here, we aim to combine the information from multiple EEG biomarkers into a diagnostic classification index in order to improve the accuracy of predicting conversion from MCI to AD within a two-year period. We followed 86 patients initially diagnosed with MCI for two years during which 25 patients converted to AD. We show that multiple EEG biomarkers mainly related to activity in the beta-frequency range (13–30 Hz can predict conversion from MCI to AD. Importantly, by integrating six EEG biomarkers into a diagnostic index using logistic regression the prediction improved compared with the classification using the individual biomarkers, with a sensitivity of 88% and specificity of 82%, compared with a sensitivity of 64% and specificity of 62% of the best individual biomarker in this index. In order to identify this diagnostic index we developed a data mining approach implemented in the Neurophysiological Biomarker Toolbox (http://www.nbtwiki.net/. We suggest that this approach can be used to identify optimal combinations of biomarkers (integrative biomarkers also in other modalities. Potentially, these integrative biomarkers could be more sensitive to disease progression and response to therapeutic intervention.

Lower Choline and Myo-Inositol in Temporo-Parietal Cortex Is Associated With Apathy in Amnestic MCI.

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Tumati, Shankar; Opmeer, Esther M; Marsman, Jan-Bernard C; Martens, Sander; Reesink, Fransje E; De Deyn, Peter P; Aleman, André

2018-01-01

Apathy is a common symptom in patients with amnestic mild cognitive impairment (aMCI) and is associated with an increased risk of progression to Alzheimer's disease (AD). The neural substrates underlying apathy in aMCI may involve multiple brain regions, including the anterior cingulate cortex and the temporo-parietal region. Here we investigated neurometabolites in brain regions that may underlie apathy in aMCI patients using proton magnetic resonance spectroscopy ( 1 H-MRS). Twenty-eight aMCI patients with varying degrees of apathy and 20 matched controls underwent 1 H-MRS. Spectra were acquired from single voxels in the posterior cingulate cortex (PCC), dorsal anterior cingulate cortex (DACC), right dorsolateral prefrontal cortex (DLPFC), and right temporo-parietal cortex (TPC). Apathy was measured with the Apathy Evaluation Scale (AES). Spearman partial correlations between metabolite concentrations in each region and severity of apathy were determined. Additionally, analyses of covariance (ANCOVA) were performed to determine whether metabolite changes differed between patients with or without clinically-diagnosed apathy. The degree of apathy was found to be negatively correlated with choline and myo-inositol (mI) in the TPC. Additional exploratory analyses suggested that N-acetylaspartate (NAA)/mI ratio was reduced in aMCI without clinical apathy but not in aMCI with clinical apathy. In the DACC, glutamate and glutamine (Glx) levels tended to be higher in the aMCI with apathy group compared to controls and reduced in association with depression scores. In conclusion, apathy in aMCI patients was associated with neurometabolite changes indicative of altered membranal integrity and glial function in the right TPC. Findings also indicated that in a clinically-diagnosed aMCI cohort, apathy symptoms may be suggestive of neural changes that are distinct from aMCI without apathy.

Lower Choline and Myo-Inositol in Temporo-Parietal Cortex Is Associated With Apathy in Amnestic MCI

Directory of Open Access Journals (Sweden)

Shankar Tumati

2018-04-01

Full Text Available Apathy is a common symptom in patients with amnestic mild cognitive impairment (aMCI and is associated with an increased risk of progression to Alzheimer’s disease (AD. The neural substrates underlying apathy in aMCI may involve multiple brain regions, including the anterior cingulate cortex and the temporo-parietal region. Here we investigated neurometabolites in brain regions that may underlie apathy in aMCI patients using proton magnetic resonance spectroscopy (1H-MRS. Twenty-eight aMCI patients with varying degrees of apathy and 20 matched controls underwent 1H-MRS. Spectra were acquired from single voxels in the posterior cingulate cortex (PCC, dorsal anterior cingulate cortex (DACC, right dorsolateral prefrontal cortex (DLPFC, and right temporo-parietal cortex (TPC. Apathy was measured with the Apathy Evaluation Scale (AES. Spearman partial correlations between metabolite concentrations in each region and severity of apathy were determined. Additionally, analyses of covariance (ANCOVA were performed to determine whether metabolite changes differed between patients with or without clinically-diagnosed apathy. The degree of apathy was found to be negatively correlated with choline and myo-inositol (mI in the TPC. Additional exploratory analyses suggested that N-acetylaspartate (NAA/mI ratio was reduced in aMCI without clinical apathy but not in aMCI with clinical apathy. In the DACC, glutamate and glutamine (Glx levels tended to be higher in the aMCI with apathy group compared to controls and reduced in association with depression scores. In conclusion, apathy in aMCI patients was associated with neurometabolite changes indicative of altered membranal integrity and glial function in the right TPC. Findings also indicated that in a clinically-diagnosed aMCI cohort, apathy symptoms may be suggestive of neural changes that are distinct from aMCI without apathy.

Multimodal Hyper-connectivity Networks for MCI Classification.

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Li, Yang; Gao, Xinqiang; Jie, Biao; Yap, Pew-Thian; Kim, Min-Jeong; Wee, Chong-Yaw; Shen, Dinggang

2017-09-01

Hyper-connectivity network is a network where every edge is connected to more than two nodes, and can be naturally denoted using a hyper-graph. Hyper-connectivity brain network, either based on structural or functional interactions among the brain regions, has been used for brain disease diagnosis. However, the conventional hyper-connectivity network is constructed solely based on single modality data, ignoring potential complementary information conveyed by other modalities. The integration of complementary information from multiple modalities has been shown to provide a more comprehensive representation about the brain disruptions. In this paper, a novel multimodal hyper-network modelling method was proposed for improving the diagnostic accuracy of mild cognitive impairment (MCI). Specifically, we first constructed a multimodal hyper-connectivity network by simultaneously considering information from diffusion tensor imaging and resting-state functional magnetic resonance imaging data. We then extracted different types of network features from the hyper-connectivity network, and further exploited a manifold regularized multi-task feature selection method to jointly select the most discriminative features. Our proposed multimodal hyper-connectivity network demonstrated a better MCI classification performance than the conventional single modality based hyper-connectivity networks.

The Test Your Memory for Mild Cognitive Impairment (TYM-MCI).

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Brown, Jeremy M; Lansdall, Claire J; Wiggins, Julie; Dawson, Kate E; Hunter, Kristina; Rowe, James B; Parker, Richard A

2017-12-01

To validate a short cognitive test: the Test Your Memory for Mild Cognitive Impairment (TYM-MCI) in the diagnosis of patients with amnestic mild cognitive impairment or mild Alzheimer's disease (aMCI/AD). Two hundred and two patients with mild memory problems were recruited. All had 'passed' the Mini-Mental State Examination (MMSE). Patients completed the TYM-MCI, the Test Your Memory test (TYM), MMSE and revised Addenbrooke's Cognitive Examination (ACE-R), had a neurological examination, clinical diagnostics and multidisciplinary team review. As a single test, the TYM-MCI performed as well as the ACE-R in the distinction of patients with aMCI/AD from patients with subjective memory impairment with a sensitivity of 0.79 and specificity of 0.91. Used in combination with the ACE-R, it provided additional value and identified almost all cases of aMCI/AD. The TYM-MCI correctly classified most patients who had equivocal ACE-R scores. Integrated discriminant improvement analysis showed that the TYM-MCI added value to the conventional memory assessment. Patients initially diagnosed as unknown or with subjective memory impairment who were later rediagnosed with aMCI/AD scored poorly on their original TYM-MCI. The TYM-MCI is a powerful short cognitive test that examines verbal and visual recall and is a valuable addition to the assessment of patients with aMCI/AD. It is simple and cheap to administer and requires minimal staff time and training. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Early identification of MCI converting to AD: a FDG PET study

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Pagani, Marco [Institute of Cognitive Sciences and Technologies, CNR, Rome (Italy); Karolinska Hospital Stockholm, Department of Nuclear Medicine, Stockholm (Sweden); Nobili, Flavio; Arnaldi, Dario; Brugnolo, Andrea; Picco, Agnese [University of Genoa and IRCCS AOU San Martino-IST, Clinical Neurology, Department of Neuroscience (DINOGMI), Genoa (Italy); Morbelli, Silvia; Bauckneht, Matteo; Piva, Roberta; Sambuceti, Gianmario [University of Genoa and IRCCS AOU San Martino-IST, Department of Nuclear Medicine, Department of Health Science (DISSAL), Genoa (Italy); Giuliani, Alessandro [Istituto Superiore di Sanita, Environment and Health Department, Rome (Italy); Oeberg, Johanna [Karolinska Hospital, Department of Hospital Physics, Stockholm (Sweden); Girtler, Nicola [University of Genoa and IRCCS AOU San Martino-IST, Clinical Neurology, Department of Neuroscience (DINOGMI), Genoa (Italy); IRCCS AOU San Martino-IST, Clinical Psychology, Genoa (Italy); Chincarini, Andrea [National Institute of Nuclear Physics (INFN), Genoa section, Genoa (Italy); Jonsson, Cathrine [Karolinska University Hospital, Medical Radiation Physics and Nuclear Medicine, Imaging and Physiology, Stockholm (Sweden); De Carli, Fabrizio [AOU San Martino-IST, Institute of Molecular Bioimaging and Physiology, CNR - Genoa Unit, Genoa (Italy)

2017-11-15

Mild cognitive impairment (MCI) is a transitional pathological stage between normal ageing (NA) and Alzheimer's disease (AD). Although subjects with MCI show a decline at different rates, some individuals remain stable or even show an improvement in their cognitive level after some years. We assessed the accuracy of FDG PET in discriminating MCI patients who converted to AD from those who did not. FDG PET was performed in 42 NA subjects, 27 MCI patients who had not converted to AD at 5 years (nc-MCI; mean follow-up time 7.5 ± 1.5 years), and 95 MCI patients who converted to AD within 5 years (MCI-AD; mean conversion time 1.8 ± 1.1 years). Relative FDG uptake values in 26 meta-volumes of interest were submitted to ANCOVA and support vector machine analyses to evaluate regional differences and discrimination accuracy. The MCI-AD group showed significantly lower FDG uptake values in the temporoparietal cortex than the other two groups. FDG uptake values in the nc-MCI group were similar to those in the NA group. Support vector machine analysis discriminated nc-MCI from MCI-AD patients with an accuracy of 89% (AUC 0.91), correctly detecting 93% of the nc-MCI patients. In MCI patients not converting to AD within a minimum follow-up time of 5 years and MCI patients converting within 5 years, baseline FDG PET and volume-based analysis identified those who converted with an accuracy of 89%. However, further analysis is needed in patients with amnestic MCI who convert to a dementia other than AD. (orig.)

Early identification of MCI converting to AD: a FDG PET study

International Nuclear Information System (INIS)

Pagani, Marco; Nobili, Flavio; Arnaldi, Dario; Brugnolo, Andrea; Picco, Agnese; Morbelli, Silvia; Bauckneht, Matteo; Piva, Roberta; Sambuceti, Gianmario; Giuliani, Alessandro; Oeberg, Johanna; Girtler, Nicola; Chincarini, Andrea; Jonsson, Cathrine; De Carli, Fabrizio

2017-01-01

Mild cognitive impairment (MCI) is a transitional pathological stage between normal ageing (NA) and Alzheimer's disease (AD). Although subjects with MCI show a decline at different rates, some individuals remain stable or even show an improvement in their cognitive level after some years. We assessed the accuracy of FDG PET in discriminating MCI patients who converted to AD from those who did not. FDG PET was performed in 42 NA subjects, 27 MCI patients who had not converted to AD at 5 years (nc-MCI; mean follow-up time 7.5 ± 1.5 years), and 95 MCI patients who converted to AD within 5 years (MCI-AD; mean conversion time 1.8 ± 1.1 years). Relative FDG uptake values in 26 meta-volumes of interest were submitted to ANCOVA and support vector machine analyses to evaluate regional differences and discrimination accuracy. The MCI-AD group showed significantly lower FDG uptake values in the temporoparietal cortex than the other two groups. FDG uptake values in the nc-MCI group were similar to those in the NA group. Support vector machine analysis discriminated nc-MCI from MCI-AD patients with an accuracy of 89% (AUC 0.91), correctly detecting 93% of the nc-MCI patients. In MCI patients not converting to AD within a minimum follow-up time of 5 years and MCI patients converting within 5 years, baseline FDG PET and volume-based analysis identified those who converted with an accuracy of 89%. However, further analysis is needed in patients with amnestic MCI who convert to a dementia other than AD. (orig.)

Comparison of the Montreal Cognitive Assessment and the Mini-Mental State Examination in detecting multi-domain mild cognitive impairment in a Chinese sub-sample drawn from a population-based study.

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Dong, YanHong; Yean Lee, Wah; Hilal, Saima; Saini, Monica; Wong, Tien Yin; Chen, Christopher Li-Hsian; Venketasubramanian, Narayanaswamy; Ikram, Mohammad Kamran

2013-11-01

We examined the discriminant validity of the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) in detecting multiple-domain mild cognitive impairment (md-MCI) in a Chinese sub-sample drawn from elderly population-based study. This study included Chinese participants from the Epidemiology of Dementia in Singapore (EDIS) study aged ≥ 60 years who underwent cognitive screening with the Abbreviated Mental Test and Progressive Forgetfulness Questionnaire. Screen-positive participants subsequently underwent MoCA, MMSE, and a comprehensive formal neuropsychological battery. MCI was defined by Petersen's criteria and further classified into single-domain MCI (sd-MCI) and md-MCI. Area under the receiver operating characteristic curve (AUC) with 95% confidence intervals (CIs) was computed for the MoCA and the MMSE in detecting md-MCI. A total of 300 participants were recruited: 128 (42.7%) were diagnosed with no cognitive impairment (NCI), 47 (15.7%) with sd-MCI, and 83 (28.0%) with md-MCI. Forty-one participants were excluded, 7 (2.3%) had dementia, and 34 (11.3%) had only objective cognitive impairment without subjective complaints. Although the MoCA had a significantly larger AUC than the MMSE (0.94 (95% CI = 0.91-0.97) vs. 0.91 (95% CI = 0.86-0.95), p= 0.04), at optimal cut-off points, the MoCA (19/20) was equivalent to the MMSE (25/26) in detecting md-MCI (sensitivity: 0.80 vs. 0.87, specificity: 0.92 vs. 0.80). Both screening tests had good discriminant validity and can be used in detecting md-MCI in a sub-sample of Chinese drawn from a population-based study.

Time-domain multiple-quantum NMR

International Nuclear Information System (INIS)

Weitekamp, D.P.

1982-11-01

The development of time-domain multiple-quantum nuclear magnetic resonance is reviewed through mid 1982 and some prospects for future development are indicated. Particular attention is given to the problem of obtaining resolved, interpretable, many-quantum spectra for anisotropic magnetically isolated systems of coupled spins. New results are presented on a number of topics including the optimization of multiple-quantum-line intensities, analysis of noise in two-dimensional spectroscopy, and the use of order-selective excitation for cross polarization between nuclear-spin species

Multiple hypothesis tracking for the cyber domain

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Schwoegler, Stefan; Blackman, Sam; Holsopple, Jared; Hirsch, Michael J.

2011-09-01

This paper discusses how methods used for conventional multiple hypothesis tracking (MHT) can be extended to domain-agnostic tracking of entities from non-kinematic constraints such as those imposed by cyber attacks in a potentially dense false alarm background. MHT is widely recognized as the premier method to avoid corrupting tracks with spurious data in the kinematic domain but it has not been extensively applied to other problem domains. The traditional approach is to tightly couple track maintenance (prediction, gating, filtering, probabilistic pruning, and target confirmation) with hypothesis management (clustering, incompatibility maintenance, hypothesis formation, and Nassociation pruning). However, by separating the domain specific track maintenance portion from the domain agnostic hypothesis management piece, we can begin to apply the wealth of knowledge gained from ground and air tracking solutions to the cyber (and other) domains. These realizations led to the creation of Raytheon's Multiple Hypothesis Extensible Tracking Architecture (MHETA). In this paper, we showcase MHETA for the cyber domain, plugging in a well established method, CUBRC's INFormation Engine for Real-time Decision making, (INFERD), for the association portion of the MHT. The result is a CyberMHT. We demonstrate the power of MHETA-INFERD using simulated data. Using metrics from both the tracking and cyber domains, we show that while no tracker is perfect, by applying MHETA-INFERD, advanced nonkinematic tracks can be captured in an automated way, perform better than non-MHT approaches, and decrease analyst response time to cyber threats.

Self-awareness of cognitive efficiency: Differences between healthy elderly and patients with mild cognitive impairment (MCI).

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Fragkiadaki, Stella; Kontaxopoulou, Dionysia; Beratis, Ion N; Andronas, Nikolaos; Economou, Alexandra; Yannis, George; Papanicolaou, Andrew; Papageorgiou, Sokratis G

2016-12-01

Self-estimation of performance implies the ability to understand one's own performance with relatively objective terms. Up to date, few studies have addressed this topic in mild cognitive impairment (MCI) patients. The aim of the present study was to compare objective measures of performance with subjective perception of specific performance on cognitive tests and investigate differences in assessment between MCI patients and healthy elderly. Thirty-five participants diagnosed with MCI (women = 16, men = 19, mean age = 65.09 years ±SD = 7.81, mean education = 12.83 years ±SD = 4.32) and 35 control subjects similar in terms of age and education (women = 20, men = 15, mean age = 62.46 years ± SD = 9.35, mean education = 14.26 ± SD = 2.84) were examined with an extended battery of neuropsychological tests. After every test they were asked to self-evaluate their performance by comparing it to what they considered as average for people of their age and educational level. This self-evaluation was reported on a scale ranging from -100 to +100. Significant differences were found in the self-assessment patterns of the two groups in memory measures of verbal and visual delayed recall, visuospatial perception, and tests of attention. MCI patients overestimated their performance on every cognitive domain while control participants underestimated their performance on measures of verbal memory. The present results indicate that accuracy of self-report is not uniform across groups and functional areas. The discrepancies in the MCI patients indicate unawareness of their memory deficits, which is contradictory to subjective memory complaints as being an important component for clinical diagnosis.

Clinical utility of FDG-PET for the clinical diagnosis in MCI.

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Arbizu, Javier; Festari, Cristina; Altomare, Daniele; Walker, Zuzana; Bouwman, Femke; Rivolta, Jasmine; Orini, Stefania; Barthel, Henryk; Agosta, Federica; Drzezga, Alexander; Nestor, Peter; Boccardi, Marina; Frisoni, Giovanni Battista; Nobili, Flavio

2018-04-27

We aim to report the quality of accuracy studies investigating the utility of [ 18 F]fluorodeoxyglucose (FDG)-PET in supporting the diagnosis of prodromal Alzheimer's Disease (AD), frontotemporal lobar degeneration (FTLD) and prodromal dementia with Lewy bodies (DLB) in mild cognitive impairment (MCI) subjects, and the corresponding recommendations made by a panel of experts. Seven panellist, four from the European Association of Nuclear Medicine, and three from the European Academy of Neurology, produced recommendations taking into consideration the incremental value of FDG-PET, as added on clinical-neuropsychological examination, to ascertain the aetiology of MCI (AD, FTLD or DLB). A literature search using harmonized population, intervention, comparison, and outcome (PICO) strings was performed, and an evidence assessment consistent with the European Federation of Neurological Societies guidance was provided. The consensual recommendation was achieved based on Delphi rounds. Fifty-four papers reported the comparison of interest. The selected papers allowed the identification of FDG patterns that characterized MCI due to AD, FTLD and DLB. While clinical outcome studies supporting the diagnosis of MCI due to AD showed varying accuracies (ranging from 58 to 100%) and varying areas under the receiver-operator characteristic curves (0.66 to 0.97), no respective data were identified for MCI due to FTLD or for MCI due to DLB. However, the high negative predictive value of FDG-PET and the existence of different disease-specific patterns of hypometabolism support the consensus recommendations for the clinical use of this imaging technique in MCI subjects. FDG-PET has clinical utility on a fair level of evidence in detecting MCI due to AD. Although promising also in detecting MCI due to FTLD and MCI due to DLB, more research is needed to ultimately judge the clinical utility of FDG-PET in these entities.

Predicting the time of conversion to MCI in the elderly: role of verbal expression and learning.

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Oulhaj, Abderrahim; Wilcock, Gordon K; Smith, A David; de Jager, Celeste A

2009-11-03

Increasing awareness that minimal or mild cognitive impairment (MCI) in the elderly may be a precursor of dementia has led to an increase in the number of people attending memory clinics. We aimed to develop a way of predicting the period of time before cognitive impairment occurs in community-dwelling elderly. The method is illustrated by the use of simple tests of different cognitive domains. A cohort of 241 normal elderly volunteers was followed for up to 20 years with regular assessments of cognitive abilities using the Cambridge Cognitive Examination (CAMCOG); 91 participants developed MCI. We used interval-censored survival analysis statistical methods to model which baseline cognitive tests best predicted the time to convert to MCI. Out of several baseline variables, only age and CAMCOG subscores for expression and learning/memory were predictors of the time to conversion. The time to conversion was 14% shorter for each 5 years of age, 17% shorter for each point lower in the expression score, and 15% shorter for each point lower in the learning score. We present in tabular form the probability of converting to MCI over intervals between 2 and 10 years for different combinations of expression and learning scores. In apparently normal elderly people, subtle measurable cognitive deficits that occur within the normal range on standard testing protocols reliably predict the time to clinically relevant cognitive impairment long before clinical symptoms are reported.

The role of social frailty in explaining the association between hearing problems and mild cognitive impairment in older adults.

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Bae, Seongryu; Lee, Sangyoon; Lee, Sungchul; Jung, Songee; Makino, Keitaro; Park, Hyuntae; Shimada, Hiroyuki

2018-06-01

We examined the role of social frailty in the association between hearing problems and mild cognitive impairment (MCI), and investigated which cognitive impairment domains are most strongly involved. Participants were 4251 older adults (mean age 72.5 ± 5.2 years, 46.1% male) who met the study inclusion criteria. Hearing problems were measured using the Hearing Handicap Inventory for the Elderly. Social frailty was identified using responses to five questions. Participants were divided into four groups depending on the presence of social frailty and hearing problems: control, social frailty, hearing problem, and co-occurrence. We assessed memory, attention, executive function, and processing speed using the National Center for Geriatrics and Gerontology-Functional Assessment Tool. Participants were categorized into normal cognition, single- and multiple-domain MCI, depending on the number of impaired cognitive domains. Participants with multiple-domain MCI exhibited the highest odds ratios (OR) of the co-occurrence group (OR: 3.89, 95% confidence intervals [CI]: 1.96-7.72), followed by the social frailty (OR: 2.65, 95% CI: 1.49-4.67), and hearing problem (OR: 1.90, 95% CI: 1.08-3.34) groups, compared with the control group. However, single-domain MCI was not significantly associated with any group. Cognitive domain analysis revealed that impaired executive function and processing speed were associated with the co-occurrence, hearing problem, and social frailty groups, respectively. Social frailty and hearing problems were independently associated with multiple-domain MCI. Comorbid conditions were more strongly associated with multiple-domain MCI. Longitudinal studies are needed to elucidate the causal role of social frailty in the association between hearing impairment and MCI. Copyright © 2018 Elsevier B.V. All rights reserved.

A Novel Study Paradigm for Long-term Prevention Trials in Alzheimer Disease: The Placebo Group Simulation Approach (PGSA): Application to MCI data from the NACC database.

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Berres, M; Kukull, W A; Miserez, A R; Monsch, A U; Monsell, S E; Spiegel, R

2014-01-01

The PGSA (Placebo Group Simulation Approach) aims at avoiding problems of sample representativeness and ethical issues typical of placebo-controlled secondary prevention trials with MCI patients. The PGSA uses mathematical modeling to forecast the distribution of quantified outcomes of MCI patient groups based on their own baseline data established at the outset of clinical trials. These forecasted distributions are then compared with the distribution of actual outcomes observed on candidate treatments, thus substituting for a concomitant placebo group. Here we investigate whether a PGSA algorithm that was developed from the MCI population of ADNI 1*, can reliably simulate the distribution of composite neuropsychological outcomes from a larger, independently selected MCI subject sample. Data available from the National Alzheimer's Coordinating Center (NACC) were used. We included 1523 patients with single or multiple domain amnestic mild cognitive impairment (aMCI) and at least two follow-ups after baseline. In order to strengthen the analysis and to verify whether there was a drift over time in the neuropsychological outcomes, the NACC subject sample was split into 3 subsamples of similar size. The previously described PGSA algorithm for the trajectory of a composite neuropsychological test battery (NTB) score was adapted to the test battery used in NACC. Nine demographic, clinical, biological and neuropsychological candidate predictors were included in a mixed model; this model and its error terms were used to simulate trajectories of the adapted NTB. The distributions of empirically observed and simulated data after 1, 2 and 3 years were very similar, with some over-estimation of decline in all 3 subgroups. The by far most important predictor of the NTB trajectories is the baseline NTB score. Other significant predictors are the MMSE baseline score and the interactions of time with ApoE4 and FAQ (functional abilities). These are essentially the same predictors

Microcystin mcyA and mcyE Gene Abundances Are Not Appropriate Indicators of Microcystin Concentrations in Lakes.

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Beversdorf, Lucas J; Chaston, Sheena D; Miller, Todd R; McMahon, Katherine D

2015-01-01

Cyanobacterial harmful algal blooms (cyanoHABs) are a primary source of water quality degradation in eutrophic lakes. The occurrence of cyanoHABs is ubiquitous and expected to increase with current climate and land use change scenarios. However, it is currently unknown what environmental parameters are important for indicating the presence of cyanoHAB toxins making them difficult to predict or even monitor on time-scales relevant to protecting public health. Using qPCR, we aimed to quantify genes within the microcystin operon (mcy) to determine which cyanobacterial taxa, and what percentage of the total cyanobacterial community, were responsible for microcystin production in four eutrophic lakes. We targeted Microcystis-16S, mcyA, and Microcystis, Planktothrix, and Anabaena-specific mcyE genes. We also measured microcystins and several biological, chemical, and physical parameters--such as temperature, lake stability, nutrients, pigments and cyanobacterial community composition (CCC)--to search for possible correlations to gene copy abundance and MC production. All four lakes contained Microcystis-mcyE genes and high percentages of toxic Microcystis, suggesting Microcystis was the dominant microcystin producer. However, all genes were highly variable temporally, and in few cases, correlated with increased temperature and nutrients as the summer progressed. Interestingly, toxin gene abundances (and biomass indicators) were anti-correlated with microcystin in all lakes except the largest lake, Lake Mendota. Similarly, gene abundance and microcystins differentially correlated to CCC in all lakes. Thus, we conclude that the presence of microcystin genes are not a useful tool for eliciting an ecological role for toxins in the environment, nor are microcystin genes (e.g. DNA) a good indicator of toxins in the environment.

Abnormal-induced theta activity supports early directed-attention network deficits in progressive MCI.

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Deiber, Marie-Pierre; Ibañez, Vicente; Missonnier, Pascal; Herrmann, François; Fazio-Costa, Lara; Gold, Gabriel; Giannakopoulos, Panteleimon

2009-09-01

The electroencephalography (EEG) theta frequency band reacts to memory and selective attention paradigms. Global theta oscillatory activity includes a posterior phase-locked component related to stimulus processing and a frontal-induced component modulated by directed attention. To investigate the presence of early deficits in the directed attention-related network in elderly individuals with mild cognitive impairment (MCI), time-frequency analysis at baseline was used to assess global and induced theta oscillatory activity (4-6Hz) during n-back working memory tasks in 29 individuals with MCI and 24 elderly controls (EC). At 1-year follow-up, 13 MCI patients were still stable and 16 had progressed. Baseline task performance was similar in stable and progressive MCI cases. Induced theta activity at baseline was significantly reduced in progressive MCI as compared to EC and stable MCI in all n-back tasks, which were similar in terms of directed attention requirements. While performance is maintained, the decrease of induced theta activity suggests early deficits in the directed-attention network in progressive MCI, whereas this network is functionally preserved in stable MCI.

Classifying MCI Subtypes in Community-Dwelling Elderly Using Cross-Sectional and Longitudinal MRI-Based Biomarkers

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Hao Guan

2017-09-01

Full Text Available Amnestic MCI (aMCI and non-amnestic MCI (naMCI are considered to differ in etiology and outcome. Accurately classifying MCI into meaningful subtypes would enable early intervention with targeted treatment. In this study, we employed structural magnetic resonance imaging (MRI for MCI subtype classification. This was carried out in a sample of 184 community-dwelling individuals (aged 73–85 years. Cortical surface based measurements were computed from longitudinal and cross-sectional scans. By introducing a feature selection algorithm, we identified a set of discriminative features, and further investigated the temporal patterns of these features. A voting classifier was trained and evaluated via 10 iterations of cross-validation. The best classification accuracies achieved were: 77% (naMCI vs. aMCI, 81% (aMCI vs. cognitively normal (CN and 70% (naMCI vs. CN. The best results for differentiating aMCI from naMCI were achieved with baseline features. Hippocampus, amygdala and frontal pole were found to be most discriminative for classifying MCI subtypes. Additionally, we observed the dynamics of classification of several MRI biomarkers. Learning the dynamics of atrophy may aid in the development of better biomarkers, as it may track the progression of cognitive impairment.

Altered causal connectivity of resting state brain networks in amnesic MCI.

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Peipeng Liang

Full Text Available Most neuroimaging studies of resting state networks in amnesic mild cognitive impairment (aMCI have concentrated on functional connectivity (FC based on instantaneous correlation in a single network. The purpose of the current study was to investigate effective connectivity in aMCI patients based on Granger causality of four important networks at resting state derived from functional magnetic resonance imaging data--default mode network (DMN, hippocampal cortical memory network (HCMN, dorsal attention network (DAN and fronto-parietal control network (FPCN. Structural and functional MRI data were collected from 16 aMCI patients and 16 age, gender-matched healthy controls. Correlation-purged Granger causality analysis was used, taking gray matter atrophy as covariates, to compare the group difference between aMCI patients and healthy controls. We found that the causal connectivity between networks in aMCI patients was significantly altered with both increases and decreases in the aMCI group as compared to healthy controls. Some alterations were significantly correlated with the disease severity as measured by mini-mental state examination (MMSE, and California verbal learning test (CVLT scores. When the whole-brain signal averaged over the entire brain was used as a nuisance co-variate, the within-group maps were significantly altered while the between-group difference maps did not. These results suggest that the alterations in causal influences may be one of the possible underlying substrates of cognitive impairments in aMCI. The present study extends and complements previous FC studies and demonstrates the coexistence of causal disconnection and compensation in aMCI patients, and thus might provide insights into biological mechanism of the disease.

Functional abilities in older adults with mild cognitive impairment.

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Burton, Catherine L; Strauss, Esther; Bunce, David; Hunter, Michael A; Hultsch, David F

2009-01-01

A classification scheme and general set of criteria for diagnosing mild cognitive impairment (MCI) were recently proposed by a multidisciplinary group of experts who met at an international symposium on MCI. One of the proposed criteria included preserved basic activities of daily living and minimal impairment in complex instrumental activities of daily living (IADLs). To investigate whether older adults with MCI classified according to the subtypes identified by the Working Group (i.e. amnestic, single non-memory domain, and multiple domain with or without a memory component) differed from cognitively intact older adults on a variety of measures indexing IADLs and to examine how well measures of IADL predict concurrent MCI status. Two hundred and fifty community-dwelling older adults, ranging in age from 66 to 92, completed self-report measures of IADLs (Lawton and Brody IADL Scale, Scales of Independent Behaviour-Revised--SIB-R) and a measure of everyday problem solving indexing IADLs (Everyday Problems Test--EPT). Ratings of participants' IADL functioning were also obtained from informants (e.g. spouse, adult child and friend). Older adults with multiple-domain MCI demonstrated poorer IADL functioning than older adults with no cognitive impairment on the EPT and the SIB-R (both self- and informant-report versions). The multiple-domain MCI participants also demonstrated poorer IADLs than MCI participants with impairments in a single cognitive domain on the self-reported SIB-R and EPT. The single-domain MCI groups demonstrated poorer IADLs than older adults without cognitive impairment on the informant-reported SIB-R and EPT. No significant group differences were found on the Lawton and Brody IADL Scale. Using the EPT and SIB-R as predictors in a multinomial regression analysis, MCI group status was reliably predicted, but the classification rate was poor. Individuals with MCI demonstrated poorer IADL functioning compared to cognitively intact older adults

Cognitive profiles in Mild Cognitive Impairment (MCI patients associated with Parkinson′s disease and cognitive disorders

Directory of Open Access Journals (Sweden)

Michele Pistacchi

2015-01-01

Full Text Available Background: Mild cognitive impairment (MCI is rapidly becoming one of the most common clinical manifestations affecting the elderly and represents an heterogeneous clinical syndrome that can be ascribed to different etiologies; the construct of MCI in Parkinson′s disease (PD (MCI-PD is more recent but the range of deficits is still variable. Early recognition and accurate classification of MCI-PD could offer opportunities for novel therapeutic interventions to improve the natural pathologic course. Objective: To investigate the clinical phenotype of amnestic mild cognitive impairment (aMCI and in patients with PD and MCI (MCI-PD. Materials and Methods: Seventy-three patients with aMCI and in 38 patients with MCI-PD were enrolled. They all underwent Mini-mental State Examination (MMSE, the Rey auditory-verbal learning test and the immediate visual memory (IVM item of the Mental Deterioration Battery, the Rey auditory-verbal learning test included the Rey-immediate (Rey-I, and the delayed recall of the word list (Rey test deferred, Rey-D. The Geriatric Depression Scale (GDS was used for mood assessment. Results: The results of the Rey-I and Rey-D and of the IVM item showed statistically significant differences between the aMCI and the MCI-PD group. The mean Rey-I and Rey-D score was significantly lower as well as the IVM score was higher in patients with aMCI than in those with MCI-PD, aMCI patients showed greater impairment in long-term memory, whereas more aMCI than MCI-PD patients had preserved attention, computation, praxis, and conceptualization. Conclusions: Our findings demonstrate that the cognitive deficit profile is specific for each of the two disorders: Memory impairment was a typical feature in aMCI patients while MCI-PD patients suffered from executive functions and visuospatial attention deficits.

Cortical hypermetabolism in MCI subjects: a compensatory mechanism?

International Nuclear Information System (INIS)

Ashraf, A.; Fan, Z.; Brooks, D.J.; Edison, P.

2015-01-01

Alzheimer's disease (AD) is associated with amyloid accumulation that takes place decades before symptoms appear. Cognitive impairment in AD is associated with reduced glucose metabolism. However, neuronal plasticity/compensatory mechanisms might come into play before the onset of dementia. The aim of this study was to determine whether there is evidence of cortical hypermetabolism as a compensatory mechanism before amyloid deposition takes place in subjects with amnestic mild cognitive impairment (aMCI). Nine AD subjects and ten aMCI subjects had both [ 11 C]PIB and [ 18 F]FDG PET scans with arterial input in order to quantify the amyloid deposition and glucose metabolism in vivo in comparison with healthy control subjects who underwent either [ 11 C]PIB or [ 18 F]FDG PET scans. The [ 11 C]PIB PET scans were quantified using [ 11 C]PIB target region to cerebellum uptake ratio images created by integrating the activity collected from 60 to 90 min, and regional cerebral glucose metabolism was quantified using spectral analysis. In MCI subjects, cortical hypermetabolism was observed in four amyloid-negative subjects and one amyloid-positive subject, while hypometabolism was seen in five other MCI subjects with high amyloid load. Subjects with hypermetabolism and low amyloid did not convert to AD during clinical follow-up for 18 months in contrast to four amyloid-positive hypometabolic subjects who did convert to AD. This preliminary study suggests that compensatory hypermetabolism can occur in aMCI subjects, particularly in those who are amyloid-negative. The increase in metabolic rate in different cortical regions with predominance in the occipital cortex may be a compensatory response to the neuronal damage occurring early in the disease process. It may also reflect recruitment of relatively minimally affected cortical regions to compensate for reduced function in the temporoparietal cortical association areas. (orig.)

Cortical hypermetabolism in MCI subjects: a compensatory mechanism?

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Ashraf, A.; Fan, Z.; Brooks, D.J.; Edison, P. [Imperial College London, Neurology Imaging Unit, Division of Brain Sciences, London (United Kingdom)

2014-09-30

Alzheimer's disease (AD) is associated with amyloid accumulation that takes place decades before symptoms appear. Cognitive impairment in AD is associated with reduced glucose metabolism. However, neuronal plasticity/compensatory mechanisms might come into play before the onset of dementia. The aim of this study was to determine whether there is evidence of cortical hypermetabolism as a compensatory mechanism before amyloid deposition takes place in subjects with amnestic mild cognitive impairment (aMCI). Nine AD subjects and ten aMCI subjects had both [{sup 11}C]PIB and [{sup 18}F]FDG PET scans with arterial input in order to quantify the amyloid deposition and glucose metabolism in vivo in comparison with healthy control subjects who underwent either [{sup 11}C]PIB or [{sup 18}F]FDG PET scans. The [{sup 11}C]PIB PET scans were quantified using [{sup 11}C]PIB target region to cerebellum uptake ratio images created by integrating the activity collected from 60 to 90 min, and regional cerebral glucose metabolism was quantified using spectral analysis. In MCI subjects, cortical hypermetabolism was observed in four amyloid-negative subjects and one amyloid-positive subject, while hypometabolism was seen in five other MCI subjects with high amyloid load. Subjects with hypermetabolism and low amyloid did not convert to AD during clinical follow-up for 18 months in contrast to four amyloid-positive hypometabolic subjects who did convert to AD. This preliminary study suggests that compensatory hypermetabolism can occur in aMCI subjects, particularly in those who are amyloid-negative. The increase in metabolic rate in different cortical regions with predominance in the occipital cortex may be a compensatory response to the neuronal damage occurring early in the disease process. It may also reflect recruitment of relatively minimally affected cortical regions to compensate for reduced function in the temporoparietal cortical association areas. (orig.)

Multiple Shooting and Time Domain Decomposition Methods

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Geiger, Michael; Körkel, Stefan; Rannacher, Rolf

2015-01-01

This book offers a comprehensive collection of the most advanced numerical techniques for the efficient and effective solution of simulation and optimization problems governed by systems of time-dependent differential equations. The contributions present various approaches to time domain decomposition, focusing on multiple shooting and parareal algorithms.  The range of topics covers theoretical analysis of the methods, as well as their algorithmic formulation and guidelines for practical implementation. Selected examples show that the discussed approaches are mandatory for the solution of challenging practical problems. The practicability and efficiency of the presented methods is illustrated by several case studies from fluid dynamics, data compression, image processing and computational biology, giving rise to possible new research topics.  This volume, resulting from the workshop Multiple Shooting and Time Domain Decomposition Methods, held in Heidelberg in May 2013, will be of great interest to applied...

Predicting conversion from MCI to AD using resting-state fMRI, graph theoretical approach and SVM.

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Hojjati, Seyed Hani; Ebrahimzadeh, Ata; Khazaee, Ali; Babajani-Feremi, Abbas

2017-04-15

We investigated identifying patients with mild cognitive impairment (MCI) who progress to Alzheimer's disease (AD), MCI converter (MCI-C), from those with MCI who do not progress to AD, MCI non-converter (MCI-NC), based on resting-state fMRI (rs-fMRI). Graph theory and machine learning approach were utilized to predict progress of patients with MCI to AD using rs-fMRI. Eighteen MCI converts (average age 73.6 years; 11 male) and 62 age-matched MCI non-converters (average age 73.0 years, 28 male) were included in this study. We trained and tested a support vector machine (SVM) to classify MCI-C from MCI-NC using features constructed based on the local and global graph measures. A novel feature selection algorithm was developed and utilized to select an optimal subset of features. Using subset of optimal features in SVM, we classified MCI-C from MCI-NC with an accuracy, sensitivity, specificity, and the area under the receiver operating characteristic (ROC) curve of 91.4%, 83.24%, 90.1%, and 0.95, respectively. Furthermore, results of our statistical analyses were used to identify the affected brain regions in AD. To the best of our knowledge, this is the first study that combines the graph measures (constructed based on rs-fMRI) with machine learning approach and accurately classify MCI-C from MCI-NC. Results of this study demonstrate potential of the proposed approach for early AD diagnosis and demonstrate capability of rs-fMRI to predict conversion from MCI to AD by identifying affected brain regions underlying this conversion. Copyright © 2017 Elsevier B.V. All rights reserved.

Designing for Mild Cognitive Impairment (MCI): A Design Anthropological Perspective.

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Collier, Guy; Kayes, Nicola; Reay, Stephen; Bill, Amanda

2017-01-01

This paper will present a design anthropological perspective on an ongoing project called 'Living Well with Mild Cognitive Impairment (MCI)'. The project explores how people with MCI (and their families) manage and respond to changes in their memory and thinking. One of the primary aims of this project is to design an online resource that will support people to 'Live Well' within the context of possible cognitive decline. The resource was originally proposed to function as a kind of online community, where users could both share and learn about home-grown strategies for managing the cognitive changes associated with MCI in everyday life. Much of this project has been guided by the methodological approach of design anthropology, which encourages project researchers and stakeholders to critically examine underlying assumptions and conceptual frameworks, which in this case revolve around the disputed MCI category. In this paper we will provide some background to the Living Well project before highlighting a number of key insights attained from design anthropology.

Addenbrooke's Cognitive Examination and Individual Domain Cut-Off Scores for Discriminating between Different Cognitive Subtypes of Parkinson's Disease.

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Berankova, Dagmar; Janousova, Eva; Mrackova, Martina; Eliasova, Ilona; Kostalova, Milena; Skutilova, Svetlana; Rektorova, Irena

2015-01-01

Objective. The main aim of this study was to verify the sensitivity and specificity of Addenbrooke's Cognitive Examination-Revised (ACE-R) in discriminating between Parkinson's disease (PD) with normal cognition (PD-NC) and PD with mild cognitive impairment (PD-MCI) and between PD-MCI and PD with dementia (PD-D). We also evaluated how ACE-R correlates with neuropsychological cognitive tests in PD. Methods. We examined three age-matched groups of PD patients diagnosed according to the Movement Disorder Society Task Force criteria: PD-NC, PD-MCI, and PD-D. ROC analysis was used to establish specific cut-off scores of ACE-R and its domains. Correlation analyses were performed between ACE-R and its subtests with relevant neuropsychological tests. Results. Statistically significant differences between groups were demonstrated in global ACE-R scores and subscores, except in the language domain. ACE-R cut-off score of 88.5 points discriminated best between PD-MCI and PD-NC (sensitivity 0.68, specificity 0.91); ACE-R of 82.5 points distinguished best between PD-MCI and PD-D (sensitivity 0.70, specificity 0.73). The verbal fluency domain of ACE-R demonstrated the best discrimination between PD-NC and PD-MCI (cut-off score 11.5; sensitivity 0.70, specificity 0.73) while the orientation/attention subscore was best between PD-MCI and PD-D (cut-off score 15.5; sensitivity 0.90, specificity 0.97). ACE-R scores except for ACE-R language correlated with specific cognitive tests of interest.

An evaluation of dose/unit area and time as key factors influencing the elicitation capacity of methylchloroisothiazolinone/methylisothiazolinone (MCI/MI) in MCI/MI-allergic patients

DEFF Research Database (Denmark)

Zachariae, Claus; Lerbaek, Anne; McNamee, Pauline M

2006-01-01

Methylchloroisothiazolinone and methylisothiazolinone (MCI/MI) contact allergy affects 1-3% of patch-tested patients in European centres. The aim of the present study was to evaluate the importance of the factors--time and concentration (dose/per unit area)--in the elicitation capacity by means...... (2 p.p.m.) of MCI/MI/unit area of the skin for 4 weeks. After a wash-out period of at least 4 weeks, the subjects were exposed to 0.094 microg/cm2 (7.5 p.p.m.) of MCI/MI/unit area of the skin for 4 weeks. The study showed the importance of both time and exposure in the elicitation process...

Alzheimer Disease Biomarkers as Outcome Measures for Clinical Trials in MCI.

Science.gov (United States)

Caroli, Anna; Prestia, Annapaola; Wade, Sara; Chen, Kewei; Ayutyanont, Napatkamon; Landau, Susan M; Madison, Cindee M; Haense, Cathleen; Herholz, Karl; Reiman, Eric M; Jagust, William J; Frisoni, Giovanni B

2015-01-01

The aim of this study was to compare the performance and power of the best-established diagnostic biological markers as outcome measures for clinical trials in patients with mild cognitive impairment (MCI). Magnetic resonance imaging, F-18 fluorodeoxyglucose positron emission tomography markers, and Alzheimer's Disease Assessment Scale-cognitive subscale were compared in terms of effect size and statistical power over different follow-up periods in 2 MCI groups, selected from Alzheimer's Disease Neuroimaging Initiative data set based on cerebrospinal fluid (abnormal cerebrospinal fluid Aβ1-42 concentration-ABETA+) or magnetic resonance imaging evidence of Alzheimer disease (positivity to hippocampal atrophy-HIPPO+). Biomarkers progression was modeled through mixed effect models. Scaled slope was chosen as measure of effect size. Biomarkers power was estimated using simulation algorithms. Seventy-four ABETA+ and 51 HIPPO+ MCI patients were included in the study. Imaging biomarkers of neurodegeneration, especially MR measurements, showed highest performance. For all biomarkers and both MCI groups, power increased with increasing follow-up time, irrespective of biomarker assessment frequency. These findings provide information about biomarker enrichment and outcome measurements that could be employed to reduce MCI patient samples and treatment duration in future clinical trials.

Advance prediction of mild cognitive impairment (MCI) using 99mTc-ECD SPECT brain blood flow imaging

International Nuclear Information System (INIS)

Kawasaki, Yohsuke

2008-01-01

Mild Cognitive Impairment (MCI) is considered as a precursor state of Alzheimer disease (AD). Single photon emission computed tomography (SPECT) brain blood flow imaging was investigated in MCI and it's relevance to the prognosis of MCI was evaluated in an attempt define the characteristics of brain blood flow imaging of MCI (amnestic MCI; aMCI) converting to AD. Ninety-two patients over 60 years old with amnesia were studied. 99m Tc-ethyl cysteinate dimer (ECD) SPECT brain blood flow examinations of the subject under drug-free conditions were conducted and imaging was analyzed according to the first clinical diagnosis. Patients given a diagnosis of MCI on the first clinical diagnosis, were examined again after 2 years and the SPECT imaging before 2 years previously was classified and analyzed. Of them, there were 35 MCI patients, converting of 13 AD patients (37.1%; aMCI), 10 MCI patients (28.6%; non-converter), 4 depression patients (11.4%; Depression type MCI (dMCI)), 1 Geriatric psychosis patient, but 7 patients dropped out. In the aMCI group, relative hypoperfusion was recognized in the posterior cingulate and the precuneus. In the dMCI group, relative hypoperfusion was recognized in the dorsolateral prefrontal cortex (DLPFC) and the anterior cingulate. In the non-converter group, relative hypoperfusion was recognized in the basal forebrain. The hypoperfusion of the precuneus in aMCI, and the hypoperfusion of the right frontal lobe (DLPFC, dorsal-anterior cingulate) in dMCI were characteristic brain blood-flow abnormalities. We believe 99m Tc-ECD SPECT brain blood flow imaging to be useful in the diagnosis of aMCI and in the early detection of depression. (author)

Five-year follow-up of 11C-PIB uptake in Alzheimer's disease and MCI

International Nuclear Information System (INIS)

Kemppainen, N.M.; Scheinin, N.M.; Koivunen, J.; Johansson, J.; Toivonen, J.T.; Naagren, K.; Rokka, J.; Rinne, J.O.; Karrasch, M.; Parkkola, R.

2014-01-01

The aim of this study was to evaluate the longitudinal changes in [ 11 C]PIB uptake in mild cognitive impairment (MCI) and Alzheimer's disease (AD) over a long-term follow-up. Six AD patients, ten MCI patients and eight healthy subjects underwent a [ 11 C]PIB PET scan at baseline and at 2 and 5 years. The clinical status of the MCI patients was evaluated every 6 months. The MCI group showed a significant increase in [ 11 C]PIB uptake over time (p 11 C]PIB scan at baseline but increased uptake later. There was an increase in [ 11 C]PIB uptake with time in the AD group (p = 0.02), but this did not significantly differ from the change in the control group. Our results revealed a significant increase in amyloid load even at the time of AD diagnosis in some of the MCI patients who converted. A positive [ 11 C]PIB scan at baseline in MCI patients strongly predicted future conversion to AD but a negative PIB scan in MCI patients did not exclude future conversion. The results suggest that there is wide individual variation in the brain amyloid load in MCI, and in the course of amyloid accumulation in relation to the clinical diagnosis of AD. (orig.)

The value of whole-brain CT perfusion imaging and CT angiography using a 320-slice CT scanner in the diagnosis of MCI and AD patients

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Zhang, Bo; Gu, Guo-jun; Jiang, Hong; Guo, Yi [Medical School of Tongji University, Department of Medical Imaging, Tongji Hospital, Shanghai (China); Shen, Xing [Traditional Chinese Hospital, Department of Radiology, Kun Shan, Jiangsu Province (China); Li, Bo; Zhang, Wei [Medical School of Jiaotong University, Department of Medical Imaging, Renji Hospital, Shanghai (China)

2017-11-15

To validate the value of whole-brain computed tomography perfusion (CTP) and CT angiography (CTA) in the diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Whole-brain CTP and four-dimensional CT angiography (4D-CTA) images were acquired in 30 MCI, 35 mild AD patients, 35 moderate AD patients, 30 severe AD patients and 50 normal controls (NC). Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and correlation between CTP and 4D-CTA were analysed. Elevated CBF in the left frontal and temporal cortex was found in MCI compared with the NC group. However, TTP was increased in the left hippocampus in mild AD patients compared with NC. In moderate and severe AD patients, hypoperfusion was found in multiple brain areas compared with NC. Finally, we found that the extent of arterial stenosis was negatively correlated with CBF in partial cerebral cortex and hippocampus, and positively correlated with TTP in these areas of AD and MCI patients. Our findings suggest that whole-brain CTP and 4D-CTA could serve as a diagnostic modality in distinguishing MCI and AD, and predicting conversion from MCI based on TTP of left hippocampus. (orig.)

The value of whole-brain CT perfusion imaging and CT angiography using a 320-slice CT scanner in the diagnosis of MCI and AD patients

International Nuclear Information System (INIS)

Zhang, Bo; Gu, Guo-jun; Jiang, Hong; Guo, Yi; Shen, Xing; Li, Bo; Zhang, Wei

2017-01-01

To validate the value of whole-brain computed tomography perfusion (CTP) and CT angiography (CTA) in the diagnosis of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Whole-brain CTP and four-dimensional CT angiography (4D-CTA) images were acquired in 30 MCI, 35 mild AD patients, 35 moderate AD patients, 30 severe AD patients and 50 normal controls (NC). Cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), time to peak (TTP), and correlation between CTP and 4D-CTA were analysed. Elevated CBF in the left frontal and temporal cortex was found in MCI compared with the NC group. However, TTP was increased in the left hippocampus in mild AD patients compared with NC. In moderate and severe AD patients, hypoperfusion was found in multiple brain areas compared with NC. Finally, we found that the extent of arterial stenosis was negatively correlated with CBF in partial cerebral cortex and hippocampus, and positively correlated with TTP in these areas of AD and MCI patients. Our findings suggest that whole-brain CTP and 4D-CTA could serve as a diagnostic modality in distinguishing MCI and AD, and predicting conversion from MCI based on TTP of left hippocampus. (orig.)

Neuropathology of mild cognitive impairment (MCI)

International Nuclear Information System (INIS)

Murayama, Shigeo; Saito, Yuko

2007-01-01

Described are retrospective pathological studies on mild cognitive impairment (MCI) of brain specimens in the brain bank of authors' institute and current clinical studies of outpatients for screening of MCI based on those pathological findings. The study projects, aided by Ministry of Health, Labour and Welfare (MHLW) from 2003 and from 2007, have aimed to develop the optimal way for prophylaxis of dementia. In the former autopsy, about 10% of the elderly dead registered in the institute are found to have pathological changes of the clinical dementia rating 0.5, in whom the early Alzheimer disease (AD), Lewy body dementia, argentaffin granular disease and neurofibrillary tangle dominant disease are involved in a similar ratio to each other. Clinically, new patients with memory complaint are first screened by neurological tests involving CT, and then those with suspicious dementia undergo the second screening (2-day hospitalization) involving MRI with VSRAD (Voxel-based Specific Regional Analysis System for AD), ECD single photon emission computed tomography (SPECT) with eZis (easy Z-score imaging system), myocardial scintigraphy with homovanillic acid (HVA)/m-iodobenzylguanidine (MIBG), and if necessary, PET with fluorodeoxyglucose (FDG), PIB (Pittsburgh Compound B, an amyloid prove) and/or 11 C-CFT and 11 C-raclopride. Further, new patients with suspicious Parkinson disease undergo the screening (3-day) of various tests involving MRI with voxel-based morphometry and VSRAD, cerebral blood flow ECD SPECT with eZis and MIBG myocardial scintigraphy. It is concluded that AD is the most important subject in MCI and systemic diseases can also affect the cognitive ability as well. (R.T.)

CSF Aβ1-42, but not p-Tau181, differentiates aMCI from SCI.

Science.gov (United States)

Rizzi, Liara; Maria Portal, Marcelle; Batista, Carlos Eduardo Alves; Missiaggia, Luciane; Roriz-Cruz, Matheus

2018-01-01

Individuals with amnestic mild cognitive impairment (aMCI) are at a high risk to develop Alzheimer's disease (AD). We compared CSF levels of biomarkers of amyloidosis (Aβ 1-42 ) and neurodegeneration (p-Tau 181 ) in individuals with aMCI and with subjective cognitive impairment (SCI) in order to ascertain diagnostic accuracy and predict the odds ratio associated with aMCI. We collected CSF of individuals clinically diagnosed with aMCI (33) and SCI (12) of a memory clinic of Southern Brazil. Levels of Aβ 1-42 and p-Tau 181 were measured by immunoenzymatic assay. Participants also underwent neuropsychological testing including the verbal memory test subscore of the Consortium to Establish a Registry for Alzheimer's Disease (VM-CERAD). CSF concentration of Aβ 1-42 was significantly lower (p: .007) and p-Tau 181 /Aβ 1-42 ratio higher (p: .014) in aMCI individuals than in SCI. However, isolate p-Tau 181 levels were not associated with aMCI (p: .166). There was a statistically significant association between Aβ 1-42 and p-Tau 181 (R 2 : 0.177; β: -4.43; p: .017). ROC AUC of CSF Aβ 1-42 was 0.768 and of the p-Tau 181 /Aβ 1-42 ratio equals 0.742. Individuals with Aβ 1-42   0.071 were at 4.6 increased odds to have aMCI (p: .043), with a 64.5% accuracy. VM-CERAD was significantly lower in aMCI than among SCI (p: .041). CSF Aβ 1-42 , but not p-Tau 181, level was significantly associated with aMCI. Copyright © 2017 Elsevier B.V. All rights reserved.

Selective Changes of Resting-State Brain Oscillations in aMCI: An fMRI Study Using ALFF

Directory of Open Access Journals (Sweden)

Zhilian Zhao

2014-01-01

Full Text Available Mild cognitive impairment (MCI refers to a transitional state between normal aging and dementia and is a syndrome with cognitive decline greater than expected for an individual’s age and educational level. As a subtype of MCI, amnestic mild cognitive impairment (aMCI most often leads to Alzheimer’s disease. This study aims to elucidate the altered brain activation in patients with aMCI using resting-state functional magnetic resonance. We observed Frequency-dependent changes in the amplitude of low-frequency fluctuations in aMCI patients (n=20, and normal subjects (n=18. At the same time, we took gray matter volume as a covariate. We found that aMCI patients had decreased amplitude of low-frequency fluctuation signal in left superior temporal gyrus, right middle temporal gyrus, right inferior parietal lobe, and right postcentral gyrus compared to the control group. Specially, aMCI patients showed increased signal in left superior and middle frontal gyrus. Our results suggested that increased activation in frontal lobe of aMCI patients may indicate effective recruitment of compensatory brain resources. This finding and interpretation may lead to the better understanding of cognitive changes of aMCI.

High Blood Caffeine Levels in MCI Linked to Lack of Progression to Dementia

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Cao, Chuanhai; Loewenstein, David A.; Lin, Xiaoyang; Zhang, Chi; Wang, Li; Duara, Ranjan; Wu, Yougui; Giannini, Alessandra; Bai, Ge; Cai, Jianfeng; Greig, Maria; Schofield, Elizabeth; Ashok, Raj; Small, Brent; Potter, Huntington; Arendash, Gary W.

2017-01-01

Although both human epidemiologic and animal model studies have suggested that caffeine/coffee protects against Alzheimer’s disease, direct human evidence for this premise has been lacking. In the present case-control study, two separate cohorts consisting of 124 total individuals (65–88 years old) were cognitively assessed and a blood sample taken for caffeine/biomarker analysis. Subjects were then monitored for cognitive status over the ensuing 2–4 year period to determine the extent to which initial plasma caffeine/biomarkers levels would be predictive of changes in cognitive status. Plasma caffeine levels at study onset were substantially lower (−51%) in mild cognitive impairment (MCI) subjects who later progressed to dementia (MCI→DEM) compared to levels in stable MCI subjects (MCI→MCI). Moreover, none of the MCI→DEM subjects had initial blood caffeine levels that were above a critical level of 1200 ng/ml, while half of stable MCI→MCI subjects had blood caffeine levels higher than that critical level. Thus, plasma caffeine levels greater than 1200 ng/ml (≈6 µM) in MCI subjects were associated with no conversion to dementia during the ensuing 2–4 year follow-up period. Among the 11 cytokines measured in plasma, three of them (GCSF, IL-10, and IL-6) were decreased in MCI→DEM subjects, but not in stable MCI→MCI subjects with high plasma caffeine levels. Coffee would appear to be the major or perhaps only source of caffeine for such stable MCI patients. This case-control study provides the first direct evidence that caffeine/coffee intake is associated with a reduced risk of dementia or delayed onset, particularly for those who already have MCI. PMID:22430531

Comparative evaluation of the two methods of fixed dose radioiodine therapy (5 mCi and 10 mCi) for the treatment of Graves' disease

International Nuclear Information System (INIS)

Fard Esfehani, A.; Dabbagh Kakhki, V.R.; Eftekhari, M.; Zarpak, B.; Fallahi Seyjani, B.; Saghari, M.

2002-01-01

Radioiodine therapy is the safest, simplest, least expensive and most effective method for treatment in most patients with Graves' disease. Due to complexity of methods for dose determination, the tendency is toward using fixed doses of I-131 for this purpose. As there is conflict for the best fixed dose, regarding it's efficiency and complication of hypothyroidism, standardized dose selection is of particular importance in treatment of Grave' disease. 59 patients with grave' disease, referred to the nuclear medicine center of Shariati Hospital from 78.5.25 were studied. In this clinical trial, the patients were randomized into two groups, one were treated with 5 mCi of 1-131 and the other received 10 mCi of the same agent. All patients were followed for two years, with 6-month intervals. Among 65 patients treated with I-131, 20 (33 9%) patients became euthyroid and 19(32.2%) became hypothyroid while relapse was noticed in 20 patients (33.9%) In The group treated by 5 mCi I-131 (33 patients), 10(30%) were euthyroid, 6(18.2%) were hypothyroid (overall cure of 48.5% while 17(51.5%) remained hyperthyroid by the end of the follow -up period(two years). From the 26 patients who were treated with 10 mCi, the euthyroid, hypothyroid and hypothyroid states were observed in 10(38.5%), 13(50%), 13(50%) and 3(11.5%) patients respectively (with an overall cure rate of 88.5%). No relationship was noted between the outcome and age, sex, size of the thyroid gland and thyroid uptake, but the relationship between the disease outcome and the amount of administered radioiodine was statistically significant (P=0.003). For most of the patients, age, sex, iodine uptake and even thyroid size play minor roles in dose selection. Although the incidence-rate of early hypothyroidism (by the end of 2 years) in the cases related with 5 mCi is less than those treated with 10 mCi, the incidence of relapse is greatly higher in the former group. In addition, it was found that long

An agent-based negotiation approach for balancing multiple coupled control domains

DEFF Research Database (Denmark)

Umair, Aisha; Clausen, Anders; Jørgensen, Bo Nørregaard

2015-01-01

Solving multi-objective multi-issue negotiation problems involving interdependent issues distributed among multiple control domains is inherent to most non-trivial cyber-physical systems. In these systems, the coordinated operation of interconnected subsystems performing autonomous control....... The proposed approach can solve negotiation problems with interdependent issues across multiple coupled control domains. We demonstrate our approach by solving a coordination problem where a Combined Heat and Power Plant must allocate electricity for three commercial greenhouses to ensure the required plant...

Multiplicity distributions in small phase-space domains in central nucleus-nucleus collisions

International Nuclear Information System (INIS)

Baechler, J.; Hoffmann, M.; Runge, K.; Schmoetten, E.; Bartke, J.; Gladysz, E.; Kowalski, M.; Stefanski, P.; Bialkowska, H.; Bock, R.; Brockmann, R.; Sandoval, A.; Buncic, P.; Ferenc, D.; Kadija, K.; Ljubicic, A. Jr.; Vranic, D.; Chase, S.I.; Harris, J.W.; Odyniec, G.; Pugh, H.G.; Rai, G.; Teitelbaum, L.; Tonse, S.; Derado, I.; Eckardt, V.; Gebauer, H.J.; Rauch, W.; Schmitz, N.; Seyboth, P.; Seyerlein, J.; Vesztergombi, G.; Eschke, J.; Heck, W.; Kabana, S.; Kuehmichel, A.; Lahanas, M.; Lee, Y.; Le Vine, M.; Margetis, S.; Renfordt, R.; Roehrich, D.; Rothard, H.; Schmidt, E.; Schneider, I.; Stock, R.; Stroebele, H.; Wenig, S.; Fleischmann, B.; Fuchs, M.; Gazdzicki, M.; Kosiec, J.; Skrzypczak, E.; Keidel, R.; Piper, A.; Puehlhofer, F.; Nappi, E.; Posa, F.; Paic, G.; Panagiotou, A.D.; Petridis, A.; Vassileiadis, G.; Pfenning, J.; Wosiek, B.

1992-10-01

Multiplicity distributions of negatively charged particles have been studied in restricted phase space intervals for central S + S, O + Au and S + Au collisions at 200 GeV/nucleon. It is shown that multiplicity distributions are well described by a negative binomial form irrespectively of the size and dimensionality of phase space domain. A clan structure analysis reveals interesting similarities between complex nuclear collisions and a simple partonic shower. The lognormal distribution agrees reasonably well with the multiplicity data in large domains, but fails in the case of small intervals. No universal scaling function was found to describe the shape of multiplicity distributions in phase space intervals of varying size. (orig.)

Working memory span in mild cognitive impairment. Influence of processing speed and cognitive reserve.

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Facal, David; Juncos-Rabadán, Onésimo; Pereiro, Arturo X; Lojo-Seoane, Cristina

2014-04-01

Mild cognitive impairment (MCI) often includes episodic memory impairment, but can also involve other types of cognitive decline. Although previous studies have shown poorer performance of MCI patients in working memory (WM) span tasks, different MCI subgroups were not studied. In the present exploratory study, 145 participants underwent extensive cognitive evaluation, which included three different WM span tasks, and were classified into the following groups: multiple-domain amnestic MCI (mda-MCI), single-domain amnestic MCI (sda-MCI), and controls. General linear model was conducted by considering the WM span tasks as the within-subject factor; the group (mda-MCI, sda-MCI, and controls) as the inter-subject factor; and processing speed, vocabulary and age as covariates. Multiple linear regression models were also used to test the influence of processing speed, vocabulary, and other cognitive reserve (CR) proxies. Results indicate different levels of impairment of WM, with more severe impairment in mda-MCI patients. The differences were still present when processing resources and CR were controlled. Between-group differences can be understood as a manifestation of the greater severity and widespread memory impairment in mda-MCI patients and may contribute to a better understanding of continuum from normal controls to mda-MCI patients. Processing speed and CR have a limited influence on WM scores, reducing but not removing differences between groups.

18F PET with flutemetamol for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI).

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Martínez, Gabriel; Vernooij, Robin Wm; Fuentes Padilla, Paulina; Zamora, Javier; Flicker, Leon; Bonfill Cosp, Xavier

2017-11-22

relevant studies and systematic reviews, and performed citation tracking using the Science Citation Index to identify any additional relevant studies. No language or date restrictions were applied to the electronic searches. We included studies that had prospectively defined cohorts with any accepted definition of MCI at time of performing the test and the use of 18 F-flutemetamol scan to evaluate the DTA of the progression from MCI to ADD or other forms of dementia. In addition, we only selected studies that applied a reference standard for Alzheimer's dementia diagnosis, for example, National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) or Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria. We screened all titles and abstracts identified in electronic-database searches. Two review authors independently selected studies for inclusion and extracted data to create two-by-two tables, showing the binary test results cross-classified with the binary reference standard. We used these data to calculate sensitivities, specificities, and their 95% confidence intervals. Two independent assessors performed quality assessment using the QUADAS-2 tool plus some additional items to assess the methodological quality of the included studies. Progression from MCI to ADD was evaluated in 243 participants from two studies. The studies reported data on 19 participants with two years of follow-up and on 224 participants with three years of follow-up. Nine (47.4%) participants converted at two years follow-up and 81 (36.2%) converted at three years of follow-up.There were concerns about participant selection and sampling in both studies. The index test domain in one study was considered unclear and in the second study it was considered at low risk of bias. For the reference standard domain, one study was considered at low risk and the second study was considered to have an

Post-hoc analysis of randomised, placebo-controlled, double-blind study (MCI186-19) of edaravone (MCI-186) in amyotrophic lateral sclerosis.

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Takei, Koji; Takahashi, Fumihiro; Liu, Shawn; Tsuda, Kikumi; Palumbo, Joseph

2017-10-01

Post-hoc analyses of the ALS Functional Rating Scale-Revised (ALSFRS-R) score data, the primary endpoint in the 24-week double-blind placebo-controlled study of edaravone (MCI186-19, NCT01492686), were performed to confirm statistical robustness of the result. The previously reported original analysis had used a last observation carried forward (LOCF) method and also excluded patients with fewer than three completed treatment cycles. The post-hoc sensitivity analyses used different statistical methods as follows: 1) including all patients regardless of treatment cycles received (ALL LOCF); 2) a mixed model for repeated measurements (MMRM) analysis; and 3) the Combined Assessment of Function and Survival (CAFS) endpoint. Findings were consistent with the original primary analysis in showing superiority of edaravone over placebo. We also investigated the distribution of change in ALSFRS-R total score across all patients in the study as well as which ALSFRS-R items and domains may have contributed to the overall efficacy findings. The distribution of changes in ALSFRS-R total score from baseline to the end of cycle 6 (ALL LOCF) shifted in favour of edaravone compared to placebo. Edaravone was descriptively favoured for each ALSFRS-R item and each of the four ALSFRS-R domains at the end of cycle 6 (ALL LOCF), suggesting a generalised effect of edaravone in slowing functional decline across all anatomical regions. The effect of edaravone appeared to be similar in patients with bulbar onset and limb onset. Together, these observations would be consistent with its putative neuroprotective effects against the development of oxidative damage unspecific to anatomical regions.

Cholinergic Enhancement of Brain Activation in Mild Cognitive Impairment (MCI during Episodic Memory Encoding

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Shannon L Risacher

2013-09-01

Full Text Available Objective: To determine the physiological impact of treatment with donepezil (Aricept on neural circuitry supporting episodic memory encoding in patients with amnestic mild cognitive impairment (MCI using functional MRI (fMRI. Methods: 18 patients with MCI and 20 age-matched healthy controls (HC were scanned twice while performing an event-related verbal episodic encoding task. MCI participants were scanned before treatment and after approximately 3 months on donepezil; HC were untreated but rescanned at the same interval. Voxel-level analyses assessed treatment effects in activation profile relative to retest changes in non-treated HC. Changes in task-related connectivity in medial temporal circuitry were also evaluated, as were associations between brain activation pattern, task-related functional connectivity, task performance, and clinical measures of cognition.Results: At baseline, the MCI group showed reduced activation during encoding relative to HC in the right medial temporal lobe (MTL; hippocampal/parahippocampal and additional regions, as well as attenuated task-related deactivation, relative to rest, in a medial parietal lobe cluster. After treatment, the MCI group showed normalized MTL activation and improved parietal deactivation. These changes were associated with cognitive performance. After treatment, the MCI group also demonstrated increased task-related functional connectivity from the right MTL cluster seed region to a network of other sites including the basal nucleus/caudate and bilateral frontal lobes. Increased functional connectivity was associated with improved task performance.Conclusions: Pharmacologic enhancement of cholinergic function in amnestic MCI is associated with changes in brain activation pattern and functional connectivity during episodic memory processing which are in turn related to increased cognitive performance. fMRI is a promising biomarker for assessing treatment related changes in brain function.

Five-year follow-up of {sup 11}C-PIB uptake in Alzheimer's disease and MCI

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Kemppainen, N.M.; Scheinin, N.M.; Koivunen, J.; Johansson, J.; Toivonen, J.T.; Naagren, K.; Rokka, J.; Rinne, J.O. [University of Turku, Turku PET Centre, P.O. Box 52, Turku (Finland); Karrasch, M. [Abo Akademi University, Department of Psychology and Logopedics, Turku (Finland); Parkkola, R. [Tampere University and Tampere University Hospital, Department of Radiology, Tampere (Finland)

2014-02-15

The aim of this study was to evaluate the longitudinal changes in [{sup 11}C]PIB uptake in mild cognitive impairment (MCI) and Alzheimer's disease (AD) over a long-term follow-up. Six AD patients, ten MCI patients and eight healthy subjects underwent a [{sup 11}C]PIB PET scan at baseline and at 2 and 5 years. The clinical status of the MCI patients was evaluated every 6 months. The MCI group showed a significant increase in [{sup 11}C]PIB uptake over time (p < 0.001), with a similar increase from baseline to 2 years (4.7 % per year) and from 2 to 5 years (5.0 % per year). Eight MCI patients (80 %) converted to AD, and two of these patients showed a normal [{sup 11}C]PIB scan at baseline but increased uptake later. There was an increase in [{sup 11}C]PIB uptake with time in the AD group (p = 0.02), but this did not significantly differ from the change in the control group. Our results revealed a significant increase in amyloid load even at the time of AD diagnosis in some of the MCI patients who converted. A positive [{sup 11}C]PIB scan at baseline in MCI patients strongly predicted future conversion to AD but a negative PIB scan in MCI patients did not exclude future conversion. The results suggest that there is wide individual variation in the brain amyloid load in MCI, and in the course of amyloid accumulation in relation to the clinical diagnosis of AD. (orig.)

The effect of bilingualism on amnestic mild cognitive impairment.

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Ossher, Lynn; Bialystok, Ellen; Craik, Fergus I M; Murphy, Kelly J; Troyer, Angela K

2013-01-01

Previous reports have found that lifelong bilingualism is associated with a delay in the onset of dementia, including Dementia of the Alzheimer's Type (DAT). Because amnestic mild cognitive impairment (aMCI) is often a transition stage between normal aging and DAT, our aim in this paper was to establish whether this delay in symptom onset for bilinguals would also be seen in the onset of symptoms of aMCI and whether this delay would be consistent in different subtypes of aMCI. We examined the effect of bilingualism on the age of diagnosis in individuals with single- or multiple-domain aMCI who were administered a battery of neuropsychological tests and questionnaires about their language and social background. Our results showed an interaction between aMCI type and language history. Only individuals diagnosed with single-domain aMCI demonstrated a later age of diagnosis for bilinguals (M = 79.4 years) than monolinguals (M = 74.9 years). This preliminary evidence suggests that the early protective advantage of bilingualism may be specific to single-domain aMCI, which is the type of aMCI most specifically associated with progression to DAT.

1H-Magnetic resonance spectroscopy in Mb. Alzheimer's and MCI patients

International Nuclear Information System (INIS)

Fankhauser, M.

2009-01-01

In this study a proton magnetic spectroscopy was conducted on 38 patients suffering from Alzheimer, 10 patients with MCI (mild cognitive impairment) and 21 elderly controls. The analyzed metabolites were N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho) and myo-Inositol (Ins). 1 H-MRS was conducted in the cingulated gyri and the centrum semiovale of 38 patients with AD, 10 patients with MCI and 21 elderly controls. A STEAM sequence was used at 1,5 Tesla. The values of NAA, Cho, Cr and Ins were measured and the ratios of NAA/Cr, NAA/Cho, Cho/Cr and Ins/Cr were statistically evaluated. The Ins/Cr Ratio in the posterior cingulated gyrus was significantly lower in the MCI group than in the DAT group (p=0,007), while the decrease of the Ins/Cr Ratio in the compared controls was not significant. The NAA/Cr ratio was not significantly different whether in patients with AD, MCI nor in the examined controls. NAA/Cho and Cho/Cr ratios were likewise not significantly different in the three groups. Our findings of an increased Ins/Cr Ratio in the AD group might indicate the beginning of glial activation in the posterior cingulated gyri. As the other examined ratios were not significantly different among the three groups, our patients may not have suffered significant neuronal loss yet. (author) [de

Disrupted Structural Brain Network in AD and aMCI: A Finding of Long Fiber Degeneration.

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Fang, Rong; Yan, Xiao-Xiao; Wu, Zhi-Yuan; Sun, Yu; Yin, Qi-Hua; Wang, Ying; Tang, Hui-Dong; Sun, Jun-Feng; Miao, Fei; Chen, Sheng-Di

2015-01-01

Although recent evidence has emerged that Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) patients show both regional brain abnormalities and topological degeneration in brain networks, our understanding of the effects of white matter fiber aberrations on brain network topology in AD and aMCI is still rudimentary. In this study, we investigated the regional volumetric aberrations and the global topological abnormalities in AD and aMCI patients. The results showed a widely distributed atrophy in both gray and white matters in the AD and aMCI groups. In particular, AD patients had weaker connectivity with long fiber length than aMCI and normal control (NC) groups, as assessed by fractional anisotropy (FA). Furthermore, the brain networks of all three groups exhibited prominent economical small-world properties. Interestingly, the topological characteristics estimated from binary brain networks showed no significant group effect, indicating a tendency of preserving an optimal topological architecture in AD and aMCI during degeneration. However, significantly longer characteristic path length was observed in the FA weighted brain networks of AD and aMCI patients, suggesting dysfunctional global integration. Moreover, the abnormality of the characteristic path length was negatively correlated with the clinical ratings of cognitive impairment. Thus, the results therefore suggested that the topological alterations in weighted brain networks of AD are induced by the loss of connectivity with long fiber lengths. Our findings provide new insights into the alterations of the brain network in AD and may indicate the predictive value of the network metrics as biomarkers of disease development.

Cognitive reserve moderates the association between functional network anti-correlations and memory in MCI.

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Franzmeier, Nicolai; Buerger, Katharina; Teipel, Stefan; Stern, Yaakov; Dichgans, Martin; Ewers, Michael

2017-02-01

Cognitive reserve (CR) shows protective effects on cognitive function in older adults. Here, we focused on the effects of CR at the functional network level. We assessed in patients with amnestic mild cognitive impairment (aMCI) whether higher CR moderates the association between low internetwork cross-talk on memory performance. In 2 independent aMCI samples (n = 76 and 93) and healthy controls (HC, n = 36), CR was assessed via years of education and intelligence (IQ). We focused on the anti-correlation between the dorsal attention network (DAN) and an anterior and posterior default mode network (DMN), assessed via sliding time window analysis of resting-state functional magnetic resonance imaging (fMRI). The DMN-DAN anti-correlation was numerically but not significantly lower in aMCI compared to HC. However, in aMCI, lower anterior DMN-DAN anti-correlation was associated with lower memory performance. This association was moderated by CR proxies, where the association between the internetwork anti-correlation and memory performance was alleviated at higher levels of education or IQ. In conclusion, lower DAN-DMN cross-talk is associated with lower memory in aMCI, where such effects are buffered by higher CR. Copyright © 2016 Elsevier Inc. All rights reserved.

A comparison of Frequency Domain Multiple Access (FDMA) and Time Domain Multiple Access (TDMA) approaches to satellite service for low data rate Earth stations

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Stevens, G.

1983-01-01

A technological and economic assessment is made of providing low data rate service to small earth stations by satellite at Ka-band. Various Frequency Domain Multiple Access (FDMA) and Time Domain Multiple Access (TDMA) scenarios are examined and compared on the basis of cost to the end user. Very small stations (1 to 2 meters in diameter) are found not to be viable alternatives to available terrestrial services. However, medium size (3 to 5 meters) earth stations appear to be very competitive if a minimum throughput of about 1.5 Mbs is maintained. This constrains the use of such terminals to large users and shared use by smaller users. No advantage was found to the use of FDMA. TDMA had a slight advantage from a total system viewpoint and a very significant advantage in the space segment (about 1/3 the required payload weight for an equivalent capacity).

The role of the DLPFC in inductive reasoning of MCI patients and normal agings: an fMRI study.

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Yang, YanHui; Liang, PeiPeng; Lu, ShengFu; Li, KunCheng; Zhong, Ning

2009-08-01

Previous studies of young people have revealed that the left dorsolateral prefrontal cortex (DLPFC) plays an important role in inductive reasoning. An fMRI experiment was performed in this study to examine whether the left DLPFC was involved in inductive reasoning of MCI patients and normal aging, and whether the activation pattern of this region was different between MCI patients and normal aging. The fMRI results indicated that MCI patients had no difference from normal aging in behavior performance (reaction time and accuracy) and the activation pattern of DLPFC. However, the BOLD response of the DLPFC region for MCI patients was weaker than that for normal aging, and the functional connectivity between the bilateral DLPFC regions for MCI patients was significantly higher than for normal aging. Taken together, these results indicated that DLPFC plays an important role in inductive reasoning of aging, and the functional abnormity of DLPFC may be an earlier marker of MCI before structural alterations.

On the Application of Joint-Domain Dictionary Mapping for Multiple Power Disturbance Assessment

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Delong Cai

2018-02-01

Full Text Available This paper proposes a joint-domain dictionary mapping method to obtain high assessment accuracy of multiple power disturbances. Firstly, in order to achieve resolutions in both the time and frequency domains, a joint-domain dictionary is proposed which consists of a discrete Hartley base and an identity matrix. Due to the low correlation between the discrete Hartley base and the identity matrix, the joint-domain dictionary mapping can separately capture the approximations of the sinusoidal components and transients. Since the mapping coefficients contain the physical quantities, the eigenvalues of each component can be effectively estimated. A quantified eigenvalue classifier was designed for identifying power disturbances using the estimated eigenvalues. The proposed method was compared with several advanced methods through simulated power disturbances under different noise conditions, and actual data from the Institute of Electrical and Electronics Engineers Power and Energy Society database. The results reveal that the joint-domain dictionary mapping technique shows good performance on parameter estimation and recognition precision, even dealing with complicated multiple power disturbances.

Depressive symptoms accelerate cognitive decline in amyloid-positive MCI patients

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Brendel, Matthias; Xiong, Guoming; Delker, Andreas [University of Munich, Department of Nuclear Medicine, Munich (Germany); Pogarell, Oliver [University of Munich, Department of Psychiatry, Munich (Germany); Bartenstein, Peter; Rominger, Axel [University of Munich, Department of Nuclear Medicine, Munich (Germany); Munich Cluster for Systems Neurology (SyNergy), Munich (Germany); Collaboration: for the Alzheimer' s Disease Neuroimaging Initiative

2015-04-01

Late-life depression even in subsyndromal stages is strongly associated with Alzheimer's disease (AD). Furthermore, brain amyloidosis is an early biomarker in subjects who subsequently suffer from AD and can be sensitively detected by amyloid PET. Therefore, we aimed to compare amyloid load and glucose metabolism in subsyndromally depressed subjects with mild cognitive impairment (MCI). [{sup 18}F]AV45 PET, [{sup 18}F]FDG PET and MRI were performed in 371 MCI subjects from the Alzheimer's Disease Neuroimaging Initiative Subjects were judged β-amyloid-positive (Aβ+; 206 patients) or β-amyloid-negative (Aβ-; 165 patients) according to [{sup 18}F]AV45 PET. Depressive symptoms were assessed by the Neuropsychiatric Inventory Questionnaire depression item 4. Subjects with depressive symptoms (65 Aβ+, 41 Aβ-) were compared with their nondepressed counterparts. Conversion rates to AD were analysed (mean follow-up time 21.5 ± 9.1 months) with regard to coexisting depressive symptoms and brain amyloid load. Aβ+ depressed subjects showed large clusters with a higher amyloid load in the frontotemporal and insular cortices (p < 0.001) with coincident hypermetabolism (p < 0.001) in the frontal cortices than nondepressed subjects. Faster progression to AD was observed in subjects with depressive symptoms (p < 0.005) and in Aβ+ subjects (p < 0.001). Coincident depressive symptoms additionally shortened the conversion time in all Aβ+ subjects (p < 0.005) and to a greater extent in those with a high amyloid load (p < 0.001). Our results clearly indicate that Aβ+ MCI subjects with depressive symptoms have an elevated amyloid load together with relative hypermetabolism of connected brain areas compared with cognitively matched nondepressed individuals. MCI subjects with high amyloid load and coexistent depressive symptoms are at high risk of faster conversion to AD. (orig.)

Depressive symptoms accelerate cognitive decline in amyloid-positive MCI patients

International Nuclear Information System (INIS)

Brendel, Matthias; Xiong, Guoming; Delker, Andreas; Pogarell, Oliver; Bartenstein, Peter; Rominger, Axel

2015-01-01

Late-life depression even in subsyndromal stages is strongly associated with Alzheimer's disease (AD). Furthermore, brain amyloidosis is an early biomarker in subjects who subsequently suffer from AD and can be sensitively detected by amyloid PET. Therefore, we aimed to compare amyloid load and glucose metabolism in subsyndromally depressed subjects with mild cognitive impairment (MCI). [ 18 F]AV45 PET, [ 18 F]FDG PET and MRI were performed in 371 MCI subjects from the Alzheimer's Disease Neuroimaging Initiative Subjects were judged β-amyloid-positive (Aβ+; 206 patients) or β-amyloid-negative (Aβ-; 165 patients) according to [ 18 F]AV45 PET. Depressive symptoms were assessed by the Neuropsychiatric Inventory Questionnaire depression item 4. Subjects with depressive symptoms (65 Aβ+, 41 Aβ-) were compared with their nondepressed counterparts. Conversion rates to AD were analysed (mean follow-up time 21.5 ± 9.1 months) with regard to coexisting depressive symptoms and brain amyloid load. Aβ+ depressed subjects showed large clusters with a higher amyloid load in the frontotemporal and insular cortices (p < 0.001) with coincident hypermetabolism (p < 0.001) in the frontal cortices than nondepressed subjects. Faster progression to AD was observed in subjects with depressive symptoms (p < 0.005) and in Aβ+ subjects (p < 0.001). Coincident depressive symptoms additionally shortened the conversion time in all Aβ+ subjects (p < 0.005) and to a greater extent in those with a high amyloid load (p < 0.001). Our results clearly indicate that Aβ+ MCI subjects with depressive symptoms have an elevated amyloid load together with relative hypermetabolism of connected brain areas compared with cognitively matched nondepressed individuals. MCI subjects with high amyloid load and coexistent depressive symptoms are at high risk of faster conversion to AD. (orig.)

Tensor-based morphometry as a neuroimaging biomarker for Alzheimer's disease: an MRI study of 676 AD, MCI, and normal subjects.

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Hua, Xue; Leow, Alex D; Parikshak, Neelroop; Lee, Suh; Chiang, Ming-Chang; Toga, Arthur W; Jack, Clifford R; Weiner, Michael W; Thompson, Paul M

2008-11-15

In one of the largest brain MRI studies to date, we used tensor-based morphometry (TBM) to create 3D maps of structural atrophy in 676 subjects with Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy elderly controls, scanned as part of the Alzheimer's Disease Neuroimaging Initiative (ADNI). Using inverse-consistent 3D non-linear elastic image registration, we warped 676 individual brain MRI volumes to a population mean geometric template. Jacobian determinant maps were created, revealing the 3D profile of local volumetric expansion and compression. We compared the anatomical distribution of atrophy in 165 AD patients (age: 75.6+/-7.6 years), 330 MCI subjects (74.8+/-7.5), and 181 controls (75.9+/-5.1). Brain atrophy in selected regions-of-interest was correlated with clinical measurements--the sum-of-boxes clinical dementia rating (CDR-SB), mini-mental state examination (MMSE), and the logical memory test scores - at voxel level followed by correction for multiple comparisons. Baseline temporal lobe atrophy correlated with current cognitive performance, future cognitive decline, and conversion from MCI to AD over the following year; it predicted future decline even in healthy subjects. Over half of the AD and MCI subjects carried the ApoE4 (apolipoprotein E4) gene, which increases risk for AD; they showed greater hippocampal and temporal lobe deficits than non-carriers. ApoE2 gene carriers--1/6 of the normal group--showed reduced ventricular expansion, suggesting a protective effect. As an automated image analysis technique, TBM reveals 3D correlations between neuroimaging markers, genes, and future clinical changes, and is highly efficient for large-scale MRI studies.

Multiple-image hiding using super resolution reconstruction in high-frequency domains

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Li, Xiao-Wei; Zhao, Wu-Xiang; Wang, Jun; Wang, Qiong-Hua

2017-12-01

In this paper, a robust multiple-image hiding method using the computer-generated integral imaging and the modified super-resolution reconstruction algorithm is proposed. In our work, the host image is first transformed into frequency domains by cellular automata (CA), to assure the quality of the stego-image, the secret images are embedded into the CA high-frequency domains. The proposed method has the following advantages: (1) robustness to geometric attacks because of the memory-distributed property of elemental images, (2) increasing quality of the reconstructed secret images as the scheme utilizes the modified super-resolution reconstruction algorithm. The simulation results show that the proposed multiple-image hiding method outperforms other similar hiding methods and is robust to some geometric attacks, e.g., Gaussian noise and JPEG compression attacks.

Does the Assessment of Recovery Capital scale reflect a single or multiple domains?

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Arndt, Stephan; Sahker, Ethan; Hedden, Suzy

2017-01-01

The goal of this study was to determine whether the 50-item Assessment of Recovery Capital scale represents a single general measure or whether multiple domains might be psychometrically useful for research or clinical applications. Data are from a cross-sectional de-identified existing program evaluation information data set with 1,138 clients entering substance use disorder treatment. Principal components and iterated factor analysis were used on the domain scores. Multiple group factor analysis provided a quasi-confirmatory factor analysis. The solution accounted for 75.24% of the total variance, suggesting that 10 factors provide a reasonably good fit. However, Tucker's congruence coefficients between the factor structure and defining weights (0.41-0.52) suggested a poor fit to the hypothesized 10-domain structure. Principal components of the 10-domain scores yielded one factor whose eigenvalue was greater than one (5.93), accounting for 75.8% of the common variance. A few domains had perceptible but small unique variance components suggesting that a few of the domains may warrant enrichment. Our findings suggest that there is one general factor, with a caveat. Using the 10 measures inflates the chance for Type I errors. Using one general measure avoids this issue, is simple to interpret, and could reduce the number of items. However, those seeking to maximally predict later recovery success may need to use the full instrument and all 10 domains.

Do MCI criteria in drug trials accurately identify subjects with predementia Alzheimer's disease?

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Visser, P; Scheltens, P; Verhey, F

2005-01-01

Background: Drugs effective in Alzheimer-type dementia have been tested in subjects with mild cognitive impairment (MCI) because these are supposed to have Alzheimer's disease in the predementia stage. Objectives: To investigate whether MCI criteria used in these drug trials can accurately diagnose subjects with predementia Alzheimer's disease. Methods: MCI criteria of the Gal-Int 11 study, InDDEx study, ADCS memory impairment study, ampakine CX 516 study, piracetam study, and Merck rofecoxib study were applied retrospectively in a cohort of 150 non-demented subjects from a memory clinic. Forty two had progressed to Alzheimer type dementia during a five year follow up period and were considered to have predementia Alzheimer's disease at baseline. Outcome measures were the odds ratio, sensitivity, specificity, and positive and negative predictive value. Results: The odds ratio of the MCI criteria for predementia Alzheimer's disease varied between 0.84 and 11. Sensitivity varied between 0.46 and 0.83 and positive predictive value between 0.43 and 0.76. None of the criteria combined a high sensitivity with a high positive predictive value. Exclusion criteria for depression led to an increase in positive predictive value and specificity at the cost of sensitivity. In subjects older than 65 years the positive predictive value was higher than in younger subjects. Conclusions: The diagnostic accuracy of MCI criteria used in trials for predementia Alzheimer's disease is low to moderate. Their use may lead to inclusion of many patients who do not have predementia Alzheimer's disease or to exclusion of many who do. Subjects with moderately severe depression should not be excluded from trials in order not to reduce the sensitivity. PMID:16170074

Serial position effects in patients with mild cognitive impairment and early and moderate Alzheimer's disease compared with healthy comparison subjects.

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Moser, B; Deisenhammer, E A; Marksteiner, J; Papousek, I; Fink, A; Weiss, E M

2014-01-01

This study aimed to investigate whether the serial position effects in memory can differentiate patients with different subtypes of mild cognitive impairment (MCI) from healthy controls and patients with different stages of Alzheimer's disease (AD). The serial position effects was tested with the CERAD word list task in 184 persons (39 healthy control subjects, 15 amnestic MCI single domain subjects, 23 amnestic MCI multiple domain subjects, 31 nonamnestic MCI subjects, 45 early or mild AD patients, and 31 moderate AD patients). With progression of dementia, memory deficits increased and the impairment in the primacy effect during the learning trials advanced, whereas the recall of recent items was less impaired. The serial position profile of nonamnestic MCI patients resembled that of healthy control subjects, whereas amnestic MCI patients showed poorer performance in all 3 positions but no significant difference as a function of serial word position. Analyses of the serial position effect may be a useful complement to clinical neuropsychological measures for distinguishing amnestic MCI patients from normal aging and patients with different stages of dementia. © 2013 S. Karger AG, Basel.

Central Decoding for Multiple Description Codes based on Domain Partitioning

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M. Spiertz

2006-01-01

Full Text Available Multiple Description Codes (MDC can be used to trade redundancy against packet loss resistance for transmitting data over lossy diversity networks. In this work we focus on MD transform coding based on domain partitioning. Compared to Vaishampayan’s quantizer based MDC, domain based MD coding is a simple approach for generating different descriptions, by using different quantizers for each description. Commonly, only the highest rate quantizer is used for reconstruction. In this paper we investigate the benefit of using the lower rate quantizers to enhance the reconstruction quality at decoder side. The comparison is done on artificial source data and on image data. 

Differences in the use of everyday technology among persons with MCI, SCI and older adults without known cognitive impairment.

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Malinowsky, Camilla; Kottorp, Anders; Wallin, Anders; Nordlund, Arto; Björklund, Eva; Melin, Ilse; Pernevik, Anette; Rosenberg, Lena; Nygård, Louise

2017-07-01

To use valid subjective reports sensible to cognitive decline is vital to identify very early signs of dementia development. Use of everyday technology (ET) has been shown to be sensitive to differentiate adults with mild cognitive impairment (MCI) from controls, but the group with subjective cognitive impairment (SCI) has not yet been examined. This study aims to investigate and compare self-perceived ability in ET use and number of ETs reported as actually used in a sample of older adults with SCI, MCI, and older adults with no known cognitive impairment, i.e. Older adults with MCI (n = 29), SCI ( n = 26), and controls (n = 30) were interviewed with the short version of the Everyday Technology Use Questionnaire (S-ETUQ) to capture self-perceived ability in ET use and number of ETs used. To generate individual measures of ability to use ET, Rasch analysis was used. The measures were then compared group-wise using ANCOVA. The numbers of ETs used were compared group-wise with ANOVA. Controls versus SCI and MCI differed significantly regarding ETs reported as used, but not SCI versus MCI. Similarly, in ability to use ET, controls versus SCI and MCI differed significantly but not SCI versus MCI. The significantly lower numbers of ETs reported as actually used and the lower ability in SCI and MCI groups compared to controls suggest that ET use is affected already in very minor cognitive decline. This indicates that self-reported ET use based on the S-ETUQ is sensitive to detect changes already in SCI.

Visualizing stages of cortical atrophy in progressive MCI from the ADNI cohort

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Eskildsen, Simon Fristed; Fonov, Vladimir; Coupé, Pierrick

Amnestic mild cognitive impairment (MCI) is considered a condition where patients are at risk of developing clinically definite Alzheimer’s disease (AD) with an annual conversion rate of approximately 15%[1]. AD is characterized by progressive brain atrophy with major impact on the cerebral cortex...... and visualize the cortical atrophy at different stages in patients who eventually converted to clinically definite AD. We selected patients with a diagnosis of MCI from the ADNI database who converted to AD during the follow-up period. T1-weighted MRI scans were collected at time of conversion(n=140...

Quantitative comparisons between experimentally measured 2-D carbon radiation and Monte Carlo impurity (MCI) code simulations

International Nuclear Information System (INIS)

Evans, T.E.; Leonard, A.W.; West, W.P.; Finkenthal, D.F.; Fenstermacher, M.E.; Porter, G.D.

1998-08-01

Experimentally measured carbon line emissions and total radiated power distributions from the DIII-D divertor and Scrape-Off Layer (SOL) are compared to those calculated with the Monte Carlo Impurity (MCI) model. A UEDGE background plasma is used in MCI with the Roth and Garcia-Rosales (RG-R) chemical sputtering model and/or one of six physical sputtering models. While results from these simulations do not reproduce all of the features seen in the experimentally measured radiation patterns, the total radiated power calculated in MCI is in relatively good agreement with that measured by the DIII-D bolometric system when the Smith78 physical sputtering model is coupled to RG-R chemical sputtering in an unaltered UEDGE plasma. Alternatively, MCI simulations done with UEDGE background ion temperatures along the divertor target plates adjusted to better match those measured in the experiment resulted in three physical sputtering models which when coupled to the RG-R model gave a total radiated power that was within 10% of measured value

A developmental screening tool for toddlers with multiple domains based on Rasch analysis.

Science.gov (United States)

Hwang, Ai-Wen; Chou, Yeh-Tai; Hsieh, Ching-Lin; Hsieh, Wu-Shiun; Liao, Hua-Fang; Wong, Alice May-Kuen

2015-01-01

Using multidomain developmental screening tools is a feasible method for pediatric health care professionals to identify children at risk of developmental problems in multiple domains simultaneously. The purpose of this study was to develop a Rasch-based tool for Multidimensional Screening in Child Development (MuSiC) for children aged 0-3 years. The MuSic was developed by constructing items bank based on three commonly used screening tools, validating with developmental status (at risk for delay or not) on five developmental domains. Parents of a convenient sample of 632 children (aged 3-35.5 months) with and without developmental delays responded to items from the three screening tools funded by health authorities in Taiwan. Item bank was determined by item fit of Rasch analysis for each of the five developmental domains (cognitive skills, language skills, gross motor skills, fine motor skills, and socioadaptive skills). Children's performance scores in logits derived in Rasch analysis were validated with developmental status for each domain using the area under receiver operating characteristic curves. MuSiC, a 75-item developmental screening tool for five domains, was derived. The diagnostic validity of all five domains was acceptable for all stages of development, except for the infant stage (≤11 months and 15 days). MuSiC can be applied simultaneously to well-child care visits as a universal screening tool for children aged 1-3 years on multiple domains. Items with sound validity for infants need to be further developed. Copyright © 2014. Published by Elsevier B.V.

Analysis of factors affecting the outcome of Graves disease patients treated with two regimens of fixed Iodine-131 doses (10 mCi and 15 mCi)

International Nuclear Information System (INIS)

Machado, Ana C.B.; Santos, Roberto B.; Chaves, Fatima R.; Romaldini, Joao H.; Ward, Laura S.

2005-01-01

Full text: The use of fixed doses of radioiodine ( 131 I) simplifies the approach to treatment for Graves' disease (GD) patients with potential cost savings. In order to evaluate factors that may affect the outcome of 2 different regimens of 131 I, we prospectively examined 128 patients with overt thyrotoxicosis from GD, as confirmed by suppressed serum TSH, presence of TRAb, increased serum T 3 and FT 4 values. Group 1 comprised 76 patients who received a fixed dose of 10 mCi and Group 2=52 patients who received a fixed dose of 15 mCi. 36 patients did not use any antithyroid drugs and 92 patients used methimazole that was withdrawn at least 5 days before radioiodine administration. Antithyroid drugs treatment was restarted at least 7 days following 131 I therapy when needed. Baseline serum TSH and FT 4 levels were measured at 3, 6, 9 and 12 months after treatment. The groups were similar concerning age, gender, smoke, eye disease, goiter size, serum T 3 , FT 4 , TRAb, anti-Tg and anti-TPO levels as well as 24-hour 131 I or Tec-uptake values and thyroid scan. Clinical outcome was evaluated at the end of 1-year follow-up and cure of hyperthyroidism was defined as clinical and laboratory evidence of either euthyroidism or hypothyroidism in the absence of antithyroid drugs. The cure rate obtained was similar in groups 1 and 2: 73.7% and 80.8%, respectively (p=0.35). Hypothyroidism was diagnosed in 56.5% and 71.15% of the patients from groups 1 and 2, respectively (p=0.13). There was no correlation between clinical features, thyroid uptake, antibodies, serum hormones and outcome. However, logistic regression analysis demonstrated that patients with larger thyroids (weight >60 g) that, consequently, received a lower dose of radioiodine in MBq/g, had 2.4 times less chance to cure (95% Cl=1.18-4.96). The use of fixed doses of radioiodine ( 131 I) simplifies the approach to treatment for Graves' disease (GD) patients with potential cost savings. In order to evaluate

A fluorescent cassette-based strategy for engineering multiple domain fusion proteins

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Khorchid Ahmad

2003-07-01

Full Text Available Abstract Background The engineering of fusion proteins has become increasingly important and most recently has formed the basis of many biosensors, protein purification systems, and classes of new drugs. Currently, most fusion proteins consist of three or fewer domains, however, more sophisticated designs could easily involve three or more domains. Using traditional subcloning strategies, this requires micromanagement of restriction enzymes sites that results in complex workaround solutions, if any at all. Results Therefore, to aid in the efficient construction of fusion proteins involving multiple domains, we have created a new expression vector that allows us to rapidly generate a library of cassettes. Cassettes have a standard vector structure based on four specific restriction endonuclease sites and using a subtle property of blunt or compatible cohesive end restriction enzymes, they can be fused in any order and number of times. Furthermore, the insertion of PCR products into our expression vector or the recombination of cassettes can be dramatically simplified by screening for the presence or absence of fluorescence. Conclusions Finally, the utility of this new strategy was demonstrated by the creation of basic cassettes for protein targeting to subcellular organelles and for protein purification using multiple affinity tags.

18F PET with florbetapir for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI).

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Martínez, Gabriel; Vernooij, Robin Wm; Fuentes Padilla, Paulina; Zamora, Javier; Bonfill Cosp, Xavier; Flicker, Leon

2017-11-22

in the reference standard in all three studies. Regarding the domain of flow and timing, two studies were considered at high risk of bias. MCI to ADD;Progression from MCI to ADD in those with a follow-up between two to less than four years had a sensitivity of 67% (95% CI 30 to 93) and a specificity of 71% (95% CI 54 to 85) by visual assessment (n = 47, 1 study).Progression from MCI to ADD in those with a follow-up between one to less than two years had a sensitivity of 89% (95% CI 78 to 95) and a specificity of 58% (95% CI 53 to 64) by visual assessment, and a sensitivity of 87% (95% CI 76 to 94) and a specificity of 51% (95% CI 45 to 56) by quantitative assessment by the standardised uptake value ratio (SUVR)(n = 401, 1 study). MCI to any form of dementia;Progression from MCI to any form of dementia in those with a follow-up between one to less than two years had a sensitivity of 67% (95% CI 9 to 99) and a specificity of 50% (95% CI 1 to 99) by visual assessment (n = 5, 1 study). MCI to any other forms of dementia (non-ADD);There was no information regarding the progression from MCI to any other form of dementia (non-ADD). Although sensitivity was good in one included study, considering the poor specificity and the limited data available in the literature, we cannot recommend routine use of 18 F-florbetapir PET in clinical practice to predict the progression from MCI to ADD.Because of the poor sensitivity and specificity, limited number of included participants, and the limited data available in the literature, we cannot recommend its routine use in clinical practice to predict the progression from MCI to any form of dementia.Because of the high financial costs of 18 F-florbetapir, clearly demonstrating the DTA and standardising the process of this modality are important prior to its wider use.

Reverters from PD-MCI to cognitively intact are at risk for future cognitive impairment: Analysis of the PPMI cohort.

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Jones, Jacob D; Kuhn, Taylor P; Szymkowicz, Sarah M

2018-02-01

Past studies have shown that a large portion of individuals with Parkinson's disease (PD) and mild cognitive impairment (MCI) will revert to a cognitively intact (CI) status in the future. Aging studies have shown that individuals who revert from MCI to CI are at increased risk for reconverting to MCI or dementia in the future. The current study examined if individuals who revert from PD-mild cognitive impairment (PD-MCI) to CI will be at increased risk for future PD-MCI and Parkinson's disease dementia (PDD). The study utilized data from the Parkinson's Progression Markers Initiative (PPMI). The sample included 364 newly diagnosed PD participants who were followed annually for up to 4 years. Based on the first and second assessments, we identified individuals who were CI at each assessment (CI-Stable) and individuals who were PD-MCI at baseline but then reverted to CI (Reversion). Analyses examined if participants in the Reversion group were at greater risk, relative to the CI-Stable group, for cognitive impairment at future assessments. Participants in the Reversion group were at greater risk for future cognitive impairment (PD-MCI or PDD) at the 2nd, 3rd and 4th annual follow-up, relative to the CI-Stable group. The Reversion group continued to be at increased risk for future cognitive impairment when adjusting for age, gender, education, depressive symptoms, and motor severity. A large proportion of individuals with PD-MCI will not show evidence of cognitive impairment within a year. However, these "reverters" continue to be at risk for future development of cognitive impairment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessing subjective quality of life domains after multiple sclerosis diagnosis disclosure.

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Mattarozzi, Katia; Casini, Federica; Baldin, Elisa; Baldini, Martina; Lugaresi, Alessandra; Milani, Paola; Pietrolongo, Erika; Gajofatto, Alberto; Leone, Maurizio; Riise, Trond; Vignatelli, Luca; D'Alessandro, Roberto

2016-04-01

An investigation of the domains Italian patients with multiple sclerosis (MS) named as constituting their quality of life over time. We assessed, in 68 patients, QoL domains using the Schedule for the Evaluation of Individual QoL: (a) before MS diagnosis disclosure, (b) thirty days after disclosure, and (c) after one and (d) four years' follow-up. The life domains most frequently named by patients were as follows: Family, Work and Finance, Hobbies, Health, Relationship with Friends and Job Effectiveness. Only Health and Job Effectiveness domains varied with time. The Health domain became a critical dimension when MS diagnosis was revealed. In addition, patients tended to be more satisfied with their health after disclosure compared to pre-diagnosis. Job Effectiveness seemed to be an important aspect until 1 year after diagnosis disclosure, but it tended to become less crucial over time. Family seems to be the most important domain over time, and psychological adaptation to MS seems to be characterized by a reconceptualization of aspects that revolve around oneself, such as professional success, rather than relational or affective factors. Evaluating the most relevant life domains for patients and their alteration over time may provide practitioners with an important tool in making health-related decisions, thus improving health outcomes and QoL. © 2015 John Wiley & Sons Ltd.

The evaluation of MCI, MI, PMI and GT on both genders with different age and dental status.

Science.gov (United States)

Bozdag, G; Sener, S

2015-01-01

The aim of this study was to measure the mandibular cortical index (MCI), mental index (MI), panoramic mandibular index (PMI) and cortical bone thickness in the zone of the gonial angle (GT) in panoramic radiographies from a large sample of males and females and to determine how they relate to patients' age, gender and dental status. 910 panoramic radiographs were obtained and grouped into age, dental status and gender. The MCI, MI, PMI and GT were analysed. Remarkable differences were observed for MCI and GT regarding gender, age groups and dental status on both sides (p PMI in females, dental status had an effect on the MI and PMI in males (p PMI (p PMI and MI measurements. The effects of age and tooth loss in the GT and MCI measurements are similar, and these indices can be accepted as more reliable in studies including both genders.

Evaluation of radioiodine therapy with fixed doses of 10 and 15 mCi in patients with Graves disease; Avaliacao da radioiodoterapia com doses fixas de 10 e 15 mCi em pacientes com doenca de Graves

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Canadas, Viviane; Vilar, Lucio; Moura, Eliane; Brito, Ana; Castellar, Enio [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Hospital das Clinicas. Servico de Endocrinologia]. E-mail: vivi2207@ig.com.br

2007-10-15

The treatment options for the hyperthyroidism of Graves' disease are antithyroid drugs, surgery and radioiodine, none of which is considered ideal, as they do not act directly on the etiopathogenesis of the disease. Radioiodine has been increasingly used as the treatment of choice because it is a safe and definitive therapy whose administration is very easy. Some authors prefer to administer higher doses in order to deliberately induce hypothyroidism, while others recommend lower doses that result in a lower incidence of hypothyroidism and a greater incidence of euthyroidism. There is no consensus for the optimal regimen of fixed doses to be used and this is the main focus of the present study, where doses of 10 and 15 mCi of {sup 131}I were compared. Among the 164 patients analyzed, 61 (37.2%) were submitted to 10 mCi and 103 (62.8%) to 15 mCi. In the longitudinal analysis it was observed that remission of the hyperthyroidism was statistically different in the sixth month (p < 0.001), being higher in the group that used the dose of 15 mCi, but similar in both groups at 12 and 24 months. It may be concluded that the administration of fixed doses of 10 and 15 mCi of {sup 131}I brought about a similar remission of the hyperthyroidism after 12 months of treatment. Moreover, the remission rate of the hyperthyroidism had no association with age, sex or previous therapy with antithyroid drugs. (author)

Prevalence and conversion to dementia of Mild Cognitive Impairment in an elderly Italian population.

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Limongi, Federica; Siviero, Paola; Noale, Marianna; Gesmundo, Antonella; Crepaldi, Gaetano; Maggi, Stefania

2017-06-01

Mild Cognitive Impairment (MCI) represents a significant risk factor for dementia but there are only a few Italian population studies on its prevalence and its rate of conversion to dementia. Aim of this study was to assess the prevalence of MCI, its subtypes, and rates of conversion to dementia 1 year later in an elderly Italian population. The data are based on an Italian multicenter population-based cohort study with both cross-sectional and longitudinal components. Two thousand three hundred thirty-seven individuals over 65 underwent screening, clinical confirmation and 1-year follow-up. The prevalence of MCI was 21.6% and the amnestic multiple domain was the most frequent subtype (63.2%). The conversion rate to dementia was 4.1% and was found only in the amnestic multiple domain and in the unclassifiable subjects, persons with cognitive deficit but neither demented nor with MCI. The prevalence of MCI in this population sample was similar to that found in other population studies using Petersen's modified MCI criteria as well as his original criteria. With regard to conversion to dementia, our results emphasize the importance to better classify the unclassifiable subjects at high risk of progression to dementia and also at risk of being undiagnosed and untreated. MCI is characterized by extreme variability and instability. Data on the prevalence and the rate of conversion from MCI to dementia are difficult to compare given the important differences from study to study especially with regard to the diagnostic criteria utilized and their operationalization.

Oxygen-saving effect of a new cardiotonic agent, MCI-154, in diseased human hearts.

Science.gov (United States)

Mori, M; Takeuchi, M; Takaoka, H; Hata, K; Hayashi, Y; Yamakawa, H; Yokoyama, M

1997-03-01

The aim of this study was to examine the left ventricular mechanoenergetic effects of a novel Ca2+ sensitizing agent, MCI-154, on diseased human hearts compared with dobutamine. Unlike conventional cardiotonic agents, a Ca2+ sensitizer that could produce a positive inotropic action by altering the responsiveness of myofilament to Ca2+ could generate force with smaller amounts of Ca2+; thus, it may potentially save energy expenditure. The left ventricular pressure-volume relation and myocardial oxygen consumption per beat (Vo2) were measured by a conductance (volume) catheter and a Webster catheter. Left ventricular contractility (Emax), systolic pressure-volume area (PVA [index of left ventricular total mechanical energy]) and Vo2 were assessed before and after infusion of MCI-154 or dobut-amine. The PVA-independent Vo2 (Vo2 mainly for excitation-contraction coupling) was assessed as the Vo2 at zero PVA. Both agents increased Emax comparably (dobutamine: from 3.55 +/- 1.10 [mean +/- SD] to 5.04 +/- 1.16 mm Hg/ml per m2, p delta PVA-independent Vo2/delta Emax) was less with MCI-154 than with dobutamine (0.14 +/- 0.18 vs. 1.10 +/- 0.80 J/mm Hg per ml per m2, p action mediated by MCI-154 could provide an energetic advantage over the conventional cardiotonic action with currently used inotropic agents.

Langevin equations with multiplicative noise: application to domain growth

International Nuclear Information System (INIS)

Sancho, J.M.; Hernandez-Machado, A.; Ramirez-Piscina, L.; Lacasta, A.M.

1993-01-01

Langevin equations of Ginzburg-Landau form with multiplicative noise, are proposed to study the effects of fluctuations in domain growth. These equations are derived from a coarse-grained methodology. The Cahn-Hilliard-Cook linear stability analysis predicts some effects in the transitory regime. We also derive numerical algorithms for the computer simulation of these equations. The numerical results corroborate the analytical productions of the linear analysis. We also present simulation results for spinodal decomposition at large times. (author). 28 refs, 2 figs

Post-hoc analysis of MCI186-17, the extension study to MCI186-16, the confirmatory double-blind, parallel-group, placebo-controlled study of edaravone in amyotrophic lateral sclerosis.

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Takahashi, Fumihiro; Takei, Koji; Tsuda, Kikumi; Palumbo, Joseph

2017-10-01

In the 24-week double-blind study of edaravone in ALS (MCI186-16), edaravone did not show a statistically significant difference versus placebo for the primary efficacy endpoint. For post-hoc analyses, two subpopulations were identified in which edaravone might be expected to show efficacy: the efficacy-expected subpopulation (EESP), defined by scores of ≥2 points on all 12 items of the ALS Functional Rating Scale-Revised (ALSFRS-R) and a percent predicted forced vital capacity (%FVC) ≥80% at baseline; and the definite/probable EESP 2 years (dpEESP2y) subpopulation which, in addition to EESP criteria, had definite or probable ALS diagnosed by El Escorial revised criteria, and disease duration of ≤2 years. In the 36-week extension study of MCI186-16, a 24-week double-blind comparison followed by 12 weeks of open-label edaravone (MCI186-17; NCT00424463), analyses of ALSFRS-R scores of the edaravone-edaravone group and edaravone-placebo group for the full analysis set (FAS) and EESP, as prospectively defined, were reported in a previous article. Here we additionally report results in patients who met dpEESP2y criteria at the baseline of MCI186-16. In the dpEESP2y, the difference in ALSFRS-R changes from 24 to 48 weeks between the edaravone-edaravone and edaravone-placebo groups was 2.79 (p = 0.0719), which was greater than the differences previously reported for the EESP and the FAS. The pattern of adverse events in the dpEESP2y did not show any additional safety findings to those from the earlier prospective study. In conclusion, this post-hoc analysis suggests a potential effect of edaravone between 24 and 48 weeks in patients meeting dpEESP2y criteria at baseline.

Does the Assessment of Recovery Capital scale reflect a single or multiple domains?

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Arndt S

2017-07-01

Full Text Available Stephan Arndt,1–3 Ethan Sahker,1,4 Suzy Hedden1 1Iowa Consortium for Substance Abuse Research and Evaluation, 2Department of Psychiatry, Carver College of Medicine, 3Department of Biostatistics, College of Public Health, 4Department of Psychological and Quantitative Foundations, Counseling Psychology Program College of Education, University of Iowa, Iowa City, IA, USA Objective: The goal of this study was to determine whether the 50-item Assessment of Recovery Capital scale represents a single general measure or whether multiple domains might be psychometrically useful for research or clinical applications. Methods: Data are from a cross-sectional de-identified existing program evaluation information data set with 1,138 clients entering substance use disorder treatment. Principal components and iterated factor analysis were used on the domain scores. Multiple group factor analysis provided a quasi-confirmatory factor analysis. Results: The solution accounted for 75.24% of the total variance, suggesting that 10 factors provide a reasonably good fit. However, Tucker’s congruence coefficients between the factor structure and defining weights (0.41–0.52 suggested a poor fit to the hypothesized 10-domain structure. Principal components of the 10-domain scores yielded one factor whose eigenvalue was greater than one (5.93, accounting for 75.8% of the common variance. A few domains had perceptible but small unique variance components suggesting that a few of the domains may warrant enrichment. Conclusion: Our findings suggest that there is one general factor, with a caveat. Using the 10 measures inflates the chance for Type I errors. Using one general measure avoids this issue, is simple to interpret, and could reduce the number of items. However, those seeking to maximally predict later recovery success may need to use the full instrument and all 10 domains. Keywords: social support, psychometrics, quality of life

Multiple functions of the von Willebrand Factor A domain in matrilins: secretion, assembly, and proteolysis

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Kanbe Katsuaki

2008-06-01

Full Text Available Abstract The von Willebrand Factor A (vWF A domain is one of the most widely distributed structural modules in cell-matrix adhesive molecules such as intergrins and extracellular matrix proteins. Mutations in the vWF A domain of matrilin-3 cause multiple epiphyseal dysplasia (MED, however the pathological mechanism remains to be determined. Previously we showed that the vWF A domain in matrilin-1 mediates formation of a filamentous matrix network through metal-ion dependent adhesion sites in the domain. Here we show two new functions of the vWF A domain in cartilage-specific matrilins (1 and 3. First, vWF A domain regulates oligomerization of matrilins. Insertion of a vWF A domain into matrilin-3 converts the formation of a mixture of matrilin-3 tetramer, trimer, and dimer into a tetramer only, while deletion of a vWF A domain from matrilin-1 converts the formation of the native matrilin-1 trimer into a mixture of trimer and dimer. Second, the vWF A domain protects matrilin-1 from proteolysis. We identified a latent proteolytic site next to the vWF A2 domain in matrilin-1, which is sensitive to the inhibitors of matrix proteases. Deletion of the abutting vWF A domain results in degradation of matrilin-1, presumably by exposing the adjacent proteolytic site. In addition, we also confirmed the vWF A domain is vital for the secretion of matrilin-3. Secretion of the mutant matrilin-3 harbouring a point mutation within the vWF A domain, as occurred in MED patients, is markedly reduced and delayed, resulting from intracellular retention of the mutant matrilin-3. Taken together, our data suggest that different mutations/deletions of the vWF A domain in matrilins may lead to distinct pathological mechanisms due to the multiple functions of the vWF A domain.

An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

DEFF Research Database (Denmark)

Wong, Mei Mei Jaslyn Elizabeth; Midtgaard, Søren Roi; Gysel, Kira

2015-01-01

of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering...

MOTORES DE COMBUSTIÓN INTERNA (MCI) OPERANDO CON MEZCLAS DE ETANOL GASOLINA: REVISIÓN

OpenAIRE

Garcia Mariaca, Alexander; Cendales Ladino, Edwin Darío; Eslava Sarmiento, Andrés Felipe

2016-01-01

En este artículo se presenta una revisión bibliográfica acerca del uso de etanol como combustible en motores de combustión interna de encendido provocado (MCI-EP). Este empieza por una breve descripción de las diversas formas de producción y principales productores en el mundo de etanol, para posteriormente profundizar en el desempeño, combustión y las emisiones en MCI-EP al operar con diferentes mezclas de etanol y gasolina convencional. Los resultados obtenidos por los diferentes autores de...

Montreal Cognitive Assessment Memory Index Score (MoCA-MIS) as a predictor of conversion from mild cognitive impairment to Alzheimer's disease.

Science.gov (United States)

Julayanont, Parunyou; Brousseau, Mélanie; Chertkow, Howard; Phillips, Natalie; Nasreddine, Ziad S

2014-04-01

To assess the usefulness of the Montreal Cognitive Assessment (MoCA) total score (MoCA-TS) and Memory Index Score (MoCA-MIS) in predicting conversion to Alzheimer's disease (AD) in individuals with mild cognitive impairment (MCI). Retrospective chart review. Community-based memory clinic. Individuals meeting Petersen's MCI criteria (N = 165). Baseline MoCA scores at MCI diagnosis were collected from charts of eligible individuals with MCI, and MoCA-TS, MoCA-MIS, and a cognitive domain index score were calculated to assess their prognostic value in predicting conversion to AD. One hundred fourteen participants progressed to AD (MCI-AD), and 51 did not (nonconverters; MCI-NC); 90.5% of participants with MCI with a MoCA-TS less than 20/30 and a MoCA-MIS less than 7/15 at baseline converted to AD within the average follow-up period of 18 months, compared with 52.7% of participants with MCI above the cutoffs on both scores. Individuals with multiple-domain amnestic MCI had the highest AD conversion rates (73.9%). Identifying individuals with MCI at high risk of conversion to AD is important clinically and for selecting appropriate subjects for therapeutic trials. Individuals with MCI with a low MoCA-TS and a low newly devised memory index score (MoCA-MIS) are at greater risk of short-term conversion to AD. © 2014, Copyright the Authors Journal compilation © 2014, The American Geriatrics Society.

Coherence and phase synchrony analyses of EEG signals in Mild Cognitive Impairment (MCI): A study of functional brain connectivity

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Handayani, Nita; Haryanto, Freddy; Khotimah, Siti Nurul; Arif, Idam; Taruno, Warsito Purwo

2018-03-01

This paper presents an EEG study for coherence and phase synchrony in mild cognitive impairment (MCI) subjects. MCI is characterized by cognitive decline, which is an early stage of Alzheimer's disease (AD). AD is a neurodegenerative disorder with symptoms such as memory loss and cognitive impairment. EEG coherence is a statistical measure of correlation between signals from electrodes spatially separated on the scalp. The magnitude of phase synchrony is expressed in the phase locking value (PLV), a statistical measure of neuronal connectivity in the human brain. Brain signals were recorded using an Emotiv Epoc 14-channel wireless EEG at a sampling frequency of 128 Hz. In this study, we used 22 elderly subjects consisted of 10 MCI subjects and 12 healthy subjects as control group. The coherence between each electrode pair was measured for all frequency bands (delta, theta, alpha and beta). In the MCI subjects, the value of coherence and phase synchrony was generally lower than in the healthy subjects especially in the beta frequency. A decline of intrahemisphere coherence in the MCI subjects occurred in the left temporo-parietal-occipital region. The pattern of decline in MCI coherence is associated with decreased cholinergic connectivity along the path that connects the temporal, occipital, and parietal areas of the brain to the frontal area of the brain. EEG coherence and phase synchrony are able to distinguish persons who suffer AD in the early stages from healthy elderly subjects.

A Robotic Solution for Assisting People with MCI at Home: Preliminary Tests of the ENRICHME System.

Science.gov (United States)

Salatino, Claudia; Pigini, Lucia; Van Kol, Marlies Maria Elisabeth; Gower, Valerio; Andrich, Renzo; Munaro, Giulia; Rosso, Roberto; Castellani, Angelo P; Farina, Elisabetta

2017-01-01

Robots have the potential to support care and independence of older adults. The ENRICHME project is developing an integrated system composed of a robot, sensors and a networking care platform, aiming at assisting older adults with MCI in their home environment. This paper reports findings of the tests performed on a sample of MCI users and their caregivers, with the first version of the ENRICHME system, in a controlled environment.

Cognitive Impairment Questionnaire (CIMP-QUEST): reported topographic symptoms in MCI and dementia.

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Astrand, R; Rolstad, S; Wallin, A

2010-06-01

The Cognitive Impairment Questionnaire (CIMP-QUEST) is an instrument based on information obtained by key informants to identify symptoms of dementia and dementia-like disorders. The questionnaire consists of three subscales reflecting impairment in parietal-temporal (PT), frontal (F) and subcortical (SC) brain regions. The questionnaire includes a memory scale and lists non-cognitive symptoms. The reliability and validity of the questionnaire were examined in 131 patients with mild cognitive impairment (MCI) or mild dementia at a university-based memory unit. Cronbach alpha for all subscales was calculated at r = 0.90. Factor analysis supported the tri-dimensionality of CIMP-QUEST's brain region-oriented construct. Test-retest reliability for a subgroup of cognitively stable MCI-patients (n = 25) was found to be r = 0.83 (P = 0.0005). The correlation between the score on the cognitive subscales (PT + F + M) and Informant Questionnaire on Cognitive Decline in the Elderly was r = 0.83 (P = 0.0005, n = 123). The memory subscale correlated significantly with episodic memory tests, the PT subscale with visuospatial and language-oriented tests, and the SC and F subscales with tests of attention, psychomotor tempo and executive function. CIMP-QUEST has high reliability and validity, and provides information about cognitive impairment and brain region-oriented symptomatology in patients with MCI and mild dementia.

Prospective memory performance in individuals with Parkinson's disease who have mild cognitive impairment.

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Costa, Alberto; Peppe, Antonella; Zabberoni, Silvia; Serafini, Francesca; Barban, Francesco; Scalici, Francesco; Caltagirone, Carlo; Carlesimo, Giovanni Augusto

2015-09-01

Prospective memory (PM) is the ability to keep in memory and realize future intentions. We aimed at investigating whether in Parkinson's disease (PD) PM deficits are related to mild cognitive impairment (MCI). Other aims were to investigate the cognitive abilities underlying PM performance, and the association between PM performance and measures of daily living functioning. The study included 15 PD patients with single domain MCI, 15 with multiple domain MCI, 17 PD patients without cognitive disorders (PDNC) and 25 healthy controls (HCs). All subjects were administered a PM procedure that included focal (PM cue is processed in the ongoing task) and nonfocal (PM cue is not processed in the ongoing task) conditions. PD patients were administered an extensive neuropsychological battery and scales to assess daily living abilities. PD patients with MCI (both single and multiple domains) showed lower accuracy on all PM conditions than both HC and PDNC patients. This was predicted by their scores on shifting indices. Conversely, PM accuracy of PDNC patients was comparable to HCs. Regression analyses revealed that PD patients' PM performance significantly predicted scores on daily living scales Conclusions: Results suggest that PM efficiency is not tout-court reduced in PD patients, but it specifically depends on the presence of MCI. Moreover, decreased executive functioning, but not episodic memory failure, accounts for a significant proportion of variance in PM performance. Finally, PM accuracy indices were found to be associated with measures of global daily living functioning and management of medication. (c) 2015 APA, all rights reserved).

A developmental screening tool for toddlers with multiple domains based on Rasch analysis

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Ai-Wen Hwang

2015-01-01

Conclusion: MuSiC can be applied simultaneously to well-child care visits as a universal screening tool for children aged 1–3 years on multiple domains. Items with sound validity for infants need to be further developed.

Longitudinal Effects of Metabolic Syndrome on Alzheimer and Vascular Related Brain Pathology

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Feng Lin

2014-06-01

Full Text Available Background/Aims: This study examines the longitudinal effect of metabolic syndrome (MetS on brain-aging indices among cognitively normal (CN and amnestic mild cognitive impairment (aMCI groups [single-domain aMCI (saMCI and multiple-domain aMCI (maMCI]. Methods: The study population included 739 participants (CN = 226, saMCI = 275, and maMCI = 238 from the Alzheimer's Disease Neuroimaging Initiative, a clinic-based, multi-center prospective cohort. Confirmatory factor analysis was employed to determine a MetS latent composite score using baseline data of vascular risk factors. We examined the changes of two Alzheimer's disease (AD biomarkers, namely [18F]fluorodeoxyglucose (FDG-positron emission tomography (PET regions of interest and medial temporal lobe volume over 5 years. A cerebrovascular aging index, cerebral white matter (cWM volume, was examined as a comparison. Results: The vascular risk was similar in all groups. Applying generalized estimating equation modeling, all brain-aging indices declined significantly over time. Higher MetS scores were associated with a faster decline of cWM in the CN and maMCI groups but with a slower decrement of regional glucose metabolism in FDG-PET in the saMCI and maMCI groups. Conclusion: At the very early stage of cognitive decline, the vascular burden such as MetS may be in parallel with or independent of AD pathology in contributing to cognitive impairment in terms of accelerating the disclosure of AD pathology.

The Montreal Cognitive Assessment is superior to the Mini-Mental State Examination in detecting patients at higher risk of dementia.

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Dong, YanHong; Lee, Wah Yean; Basri, Nur Adilah; Collinson, Simon Lowes; Merchant, Reshma A; Venketasubramanian, Narayanaswamy; Chen, Christopher Li-Hsian

2012-11-01

To examine the discriminant validity of the Montreal Cognitive Assessment (MoCA) and the Mini-Mental State Examination (MMSE) in detecting patients with cognitive impairment at higher risk for dementia at a memory clinic setting. Memory clinic patients were administered the MoCA, MMSE, and a comprehensive formal neuropsychological battery. Mild cognitive impairment (MCI) subtypes were dichotomized into two groups: single domain-MCI (sd-MCI) and multiple domain-MCI (md-MCI). Area under the receiver operating characteristic curve (ROC) analysis was used to compare the discriminatory ability of the MoCA and the MMSE. Two hundred thirty patients were recruited, of which 136 (59.1%) were diagnosed with dementia, 61 (26.5%) with MCI, and 33 (14.3%) with no cognitive impairment (NCI). The majority of MCI patients had md-MCI (n = 36, 59%). The MoCA had significantly larger AUCs than the MMSE in discriminating md-MCI from the lower risk group for incident dementia (NCI and sd-MCI) [MoCA 0.92 (95% CI, 0.86-0.98) vs. MMSE 0.84 (95% CI, 0.75-0.92), p = 0.02). At their optimal cut-off points, the MoCA (19/20) remained superior to the MMSE (23/24) in detecting md-MCI [sensitivity: 0.83 vs. 0.72; specificity: 0.86 vs. 0.83; PPV: 0.79 vs. 0.72; NPV: 0.89 vs. 0.83; correctly classified: 85.1% vs. 78.7%]. The MoCA is superior to the MMSE in the detection of patients with cognitive impairment at higher risk for incident dementia at a memory clinic setting.

Awareness of deficits in mild cognitive impairment and Alzheimer's disease: do MCI patients have impaired insight

DEFF Research Database (Denmark)

Vogel, Asmus; Stokholm, Jette; Gade, Anders

2004-01-01

In this study we investigated impaired awareness of cognitive deficits in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Very few studies have addressed this topic, and methodological inconsistencies make the comparison of previous studies difficult. From a prospective...... heterogeneity in the clinical presentation of awareness. The results demonstrate that subjective memory problems should not be a mandatory prerequisite in suspected dementia or MCI, which makes reports from informants together with thorough clinical interview and observation central when assessing suspected...

Amnestic MCI Patients' Perspectives toward Disclosure of Amyloid PET Results in a Research Context.

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Vanderschaeghe, Gwendolien; Schaeverbeke, Jolien; Vandenberghe, Rik; Dierickx, Kris

2017-01-01

Researchers currently are not obligated to share individual research results (IRR) with participants. This non-disclosure policy has been challenged on the basis of participants' rights to be aware and in control of their personal medical information. Here, we determined how patients view disclosure of research PET results of brain amyloid and why they believe it is advantageous or disadvantageous to disclose. As a part of a larger diagnostic trial, we conducted semi-structured interviews with patients with amnestic Mild Cognitive Impairment (aMCI). Participants had the option to receive their brain amyloid PET scan result (i.e., their IRR). Interviews were conducted before they received their IRR. A total of 38 aMCI patients (100% of study participants) wanted to know their IRR. The two most frequently mentioned reasons for choosing IRR disclosure were to better understand their brain health status and to be better able to make informed decisions about future personal arrangements (e.g., inheritance tax, moving into a smaller house, end-of-life decisions, etc.). Emotional risk was mentioned as the primary disadvantage of knowing one's IRR. On the other hand, non-disclosure was considered to be emotionally difficult also, as patients would be uncertain about their future health condition. Many patients diagnosed clinically with aMCI want to know their brain amyloid test results, even though this knowledge may be disadvantageous to them. Knowing what is going on with their health and the ability to make informed decisions about their future were the two principal advantages mentioned for obtaining their amyloid PET results. Because of the overwhelming consensus of aMCI patients was to disclose their brain amyloid PET scan results, researchers should strongly consider releasing this information to research subjects.

Cognitive Training Program to Improve Working Memory in Older Adults with MCI.

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Hyer, Lee; Scott, Ciera; Atkinson, Mary Michael; Mullen, Christine M; Lee, Anna; Johnson, Aaron; Mckenzie, Laura C

2016-01-01

Deficits in working memory (WM) are associated with age-related decline. We report findings from a clinical trial that examined the effectiveness of Cogmed, a computerized program that trains WM. We compare this program to a Sham condition in older adults with Mild Cognitive Impairment (MCI). Older adults (N = 68) living in the community were assessed. Participants reported memory impairment and met criteria for MCI, either by poor delayed memory or poor performance in other cognitive areas. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS, Delayed Memory Index) and the Clinical Dementia Rating scale (CDR) were utilized. All presented with normal Mini Mental State Exams (MMSE) and activities of daily living (ADLs). Participants were randomized to Cogmed or a Sham computer program. Twenty-five sessions were completed over five to seven weeks. Pre, post, and follow-up measures included a battery of cognitive measures (three WM tests), a subjective memory scale, and a functional measure. Both intervention groups improved over time. Cogmed significantly outperformed Sham on Span Board and exceeded in subjective memory reports at follow-up as assessed by the Cognitive Failures Questionnaire (CFQ). The Cogmed group demonstrated better performance on the Functional Activities Questionnaire (FAQ), a measure of adjustment and far transfer, at follow-up. Both groups, especially Cogmed, enjoyed the intervention. Results suggest that WM was enhanced in both groups of older adults with MCI. Cogmed was better on one core WM measure and had higher ratings of satisfaction. The Sham condition declined on adjustment.

Adenosine A2A Receptor and IL-10 in Peripheral Blood Mononuclear Cells of Patients with Mild Cognitive Impairment

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Beatrice Arosio

2011-01-01

Full Text Available Adenosine suppresses immune responses through the A2A receptor (A2AR. This study investigated the interleukin 10 (IL-10 genetic profile and the expression of A2AR in peripheral blood mononuclear cells (PBMCs of patients with mild cognitive impairment (MCI, Alzheimer disease (AD, and age-matched controls to verify, if they may help distinguish different forms of cognitive decline. We analyzed the IL-10 genotype and the expression of A2AR in 41 subjects with AD, 10 with amnestic MCI (a-MCI, 49 with multiple cognitive domain MCI (mcd-MCI, and 46 controls. There was a significant linear increase in A2AR mRNA levels and A2AR density from mcd-MCI to a-MCI, with intermediate levels being found in AD. The IL-10 AA genotype frequency was 67% in a-MCI, 46% in AD, 35% in mcd-MCI, and 20% in controls. These data suggest that the assessment of the IL-10 genotype and the expression of A2AR in PBMCs may be a valuable means of differentiating between a-MCI and mcd-MCI.

Contact sensitization to 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one (MCI/MI). A European multicentre study

DEFF Research Database (Denmark)

Menné, T; Frosch, P J; Veien, Niels

1991-01-01

, formaldehyde, paraben-mix, and MCI/MI. 19.4% of the patients had positive patch tests to nickel, making this the most common allergen. 3% of the patients reacted to 100 ppm MCI/MI, while 2.6% reacted to formaldehyde and 1.1% to parabens. There was great variation in the frequency of MCI/MI sensitivity among...

Generating multiple orbital angular momentum vortex beams using a metasurface in radio frequency domain

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Yu, Shixing; Li, Long, E-mail: lilong@mail.xidian.edu.cn, E-mail: gmshi@xidian.edu.cn; Shi, Guangming, E-mail: lilong@mail.xidian.edu.cn, E-mail: gmshi@xidian.edu.cn; Zhu, Cheng; Shi, Yan [National Key Laboratory of Antennas and Microwave Technology, School of Electronic Engineering, Collaborative Innovation Center of Information Sensing and Understanding, Xidian University, Xi' an 710071 (China)

2016-06-13

In this paper, an electromagnetic metasurface is designed, fabricated, and experimentally demonstrated to generate multiple orbital angular momentum (OAM) vortex beams in radio frequency domain. Theoretical formula of compensated phase-shift distribution is deduced and used to design the metasurface to produce multiple vortex radio waves in different directions with different OAM modes. The prototype of a practical configuration of square-patch metasurface is designed, fabricated, and measured to validate the theoretical analysis at 5.8 GHz. The simulated and experimental results verify that multiple OAM vortex waves can be simultaneously generated by using a single electromagnetic metasurface. The proposed method paves an effective way to generate multiple OAM vortex waves in radio and microwave wireless communication applications.

A novel biomarker of amnestic MCI based on dynamic Cross-Frequency Coupling patterns during cognitive brain responses

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Stavros I Dimitriadis

2015-10-01

Full Text Available The detection of mild cognitive impairment (MCI, the transitional stage between normal cognitive changes of aging and the cognitive decline caused by AD, is of paramount clinical importance, since MCI patients are at increased risk of progressing into AD. Electroencephalographic (EEG alterations in the spectral content of brainwaves and connectivity at resting state have been associated with early-stage AD. Recently, cognitive event-related potentials (ERPs have entered into the picture as an easy to perform screening test. Motivated by the recent findings about the role of cross-frequency coupling (CFC in cognition, we introduce a relevant methodological approach for detecting MCI based on cognitive responses from a standard auditory oddball paradigm. By using the single trial signals recorded at Pz sensor and comparing the responses to target and non-target stimuli, we first demonstrate that increased CFC is associated with the cognitive task. Then, considering the dynamic character of CFC, we identify instances during which the coupling between particular pairs of brainwave frequencies carries sufficient information for discriminating between normal subjects and patients with MCI. In this way, we form a multiparametric signature of impaired cognition. The new composite biomarker was tested using data from a cohort that consists of 25 amnestic MCI patients and 15 age-matched controls. Standard machine-learning algorithms were employed so as to implement the binary classification task. Based on leave-one-out cross-validation, the measured classification rate was found reaching very high levels (95%. Our approach compares favorably with the traditional alternative of using the morphology of averaged ERP response to make the diagnosis and the usage of features from spectro-temporal analysis of single-trial response. This further indicates that task-related CFC measurements can provide invaluable analytics in AD diagnosis and prognosis.

Curvelet-domain multiple matching method combined with cubic B-spline function

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Wang, Tong; Wang, Deli; Tian, Mi; Hu, Bin; Liu, Chengming

2018-05-01

Since the large amount of surface-related multiple existed in the marine data would influence the results of data processing and interpretation seriously, many researchers had attempted to develop effective methods to remove them. The most successful surface-related multiple elimination method was proposed based on data-driven theory. However, the elimination effect was unsatisfactory due to the existence of amplitude and phase errors. Although the subsequent curvelet-domain multiple-primary separation method achieved better results, poor computational efficiency prevented its application. In this paper, we adopt the cubic B-spline function to improve the traditional curvelet multiple matching method. First, select a little number of unknowns as the basis points of the matching coefficient; second, apply the cubic B-spline function on these basis points to reconstruct the matching array; third, build constraint solving equation based on the relationships of predicted multiple, matching coefficients, and actual data; finally, use the BFGS algorithm to iterate and realize the fast-solving sparse constraint of multiple matching algorithm. Moreover, the soft-threshold method is used to make the method perform better. With the cubic B-spline function, the differences between predicted multiple and original data diminish, which results in less processing time to obtain optimal solutions and fewer iterative loops in the solving procedure based on the L1 norm constraint. The applications to synthetic and field-derived data both validate the practicability and validity of the method.

Neurogranin as a predictor of memory and executive function decline in MCI patients.

Science.gov (United States)

Headley, Alison; De Leon-Benedetti, Andres; Dong, Chuanhui; Levin, Bonnie; Loewenstein, David; Camargo, Christian; Rundek, Tatjana; Zetterberg, Henrik; Blennow, Kaj; Wright, Clinton B; Sun, Xiaoyan

2018-03-06

To determine whether high CSF levels of neurogranin (Ng) predict longitudinal decline in memory and executive function during early-stage Alzheimer disease (AD). Baseline levels of CSF Ng were studied in relation to cross-sectional and longitudinal cognitive performance over 8 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative database, and participants with normal cognition (n = 111) and mild cognitive impairment (MCI) (n = 193) were included. High levels of CSF Ng were associated with poor baseline memory scores (β = -0.21, p the rate of decline by tertiles was examined, CSF Ng was a level-dependent predictor of memory function, whereby the group with highest levels of Ng showed the fastest rates of decline in both memory and executive function. When examined separately, elevated Ng was associated with cognitive decline in participants with MCI but not in those with normal cognition. The levels of CSF Ng were not associated with cognitive measures when tau and amyloid 42 (Aβ 42 ) were controlled for in these analyses. High CSF Ng associates with poor memory scores in participants with MCI cross-sectionally and with poor memory and executive function longitudinally. The association of Ng with cognitive measures disappears when tau and Aβ 42 are included in the statistical models. Our findings suggest that CSF Ng may serve as a biomarker of cognition. Synaptic dysfunction contributes to cognitive impairment in early-stage AD. © 2018 American Academy of Neurology.

Predicting Stability of Mild Cognitive Impairment (MCI): Findings of a Community Based Sample

NARCIS (Netherlands)

Ellendt, S.; Vobeta, B.; Kohn, N.; Wagels, L.; Goerlich, K.S.; Drexler, E.; Schneider, F.; Habel, U.

2017-01-01

BACKGROUND: Mild Cognitive Impairment (MCI) is a risk factor for Alzheimer's disease (AD) and other forms of dementia. However, much heterogeneity concerning neuropsychological measures, prevalence and progression rates impedes distinct diagnosis and treatment implications. OBJECTIVE: Aim of the

Hippocampal volume and CDR-SB can predict conversion to dementia in MCI patients

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João Guilherme Fiorani Borgio

2012-11-01

Full Text Available OBJECTIVE: To evaluate the combination of two factors: clinical dementia rating sum of boxes scores (CDR-SB and hippocampal volume (HV as predictors of conversion from mild cognitive impairment (MCI to dementia. METHODS: Twenty-eight individuals (9 normal and 19 with MCI were classified according to their CDR sum of boxes scores into 3 groups. RESULTS: The hippocampal volume was significantly lower in the high-risk group and in those who developed dementia after two years. The rate of conversion was crescent among the three groups. CONCLUSION: We were proposed an additional measurement of the hippocampal volume which may be helpful in the prognosis. However, we noted that the CDR-SB is a method as efficient as neuroimaging to predict dementia with the advantage of being a procedure for low cost and easy implementation, more consistent with public policy.

"You've got a friend in me": can social networks mediate the relationship between mood and MCI?

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Yates, Jennifer A; Clare, Linda; Woods, Robert T

2017-07-13

Social networks can change with age, for reasons that are adaptive or unwanted. Social engagement is beneficial to both mental health and cognition, and represents a potentially modifiable factor. Consequently this study explored this association and assessed whether the relationship between mild cognitive impairment (MCI) and mood problems was mediated by social networks. This study includes an analysis of data from the Cognitive Function and Ageing Study Wales (CFAS Wales). CFAS Wales Phase 1 data were collected from 2010 to 2013 by conducting structured interviews with older people aged over 65 years of age living in urban and rural areas of Wales, and included questions that assessed cognitive functioning, mood, and social networks. Regression analyses were used to investigate the associations between individual variables and the mediating role of social networks. Having richer social networks was beneficial to both mood and cognition. Participants in the MCI category had weaker social networks than participants without cognitive impairment, whereas stronger social networks were associated with a decrease in the odds of experiencing mood problems, suggesting that they may offer a protective effect against anxiety and depression. Regression analyses revealed that social networks are a significant mediator of the relationship between MCI and mood problems. These findings are important, as mood problems are a risk factor for progression from MCI to dementia, so interventions that increase and strengthen social networks may have beneficial effects on slowing the progression of cognitive decline.

ADMultiImg: a novel missing modality transfer learning based CAD system for diagnosis of MCI due to AD using incomplete multi-modality imaging data

Science.gov (United States)

Liu, Xiaonan; Chen, Kewei; Wu, Teresa; Weidman, David; Lure, Fleming; Li, Jing

2018-02-01

Alzheimer's Disease (AD) is the most common cause of dementia and currently has no cure. Treatments targeting early stages of AD such as Mild Cognitive Impairment (MCI) may be most effective to deaccelerate AD, thus attracting increasing attention. However, MCI has substantial heterogeneity in that it can be caused by various underlying conditions, not only AD. To detect MCI due to AD, NIA-AA published updated consensus criteria in 2011, in which the use of multi-modality images was highlighted as one of the most promising methods. It is of great interest to develop a CAD system based on automatic, quantitative analysis of multi-modality images and machine learning algorithms to help physicians more adequately diagnose MCI due to AD. The challenge, however, is that multi-modality images are not universally available for many patients due to cost, access, safety, and lack of consent. We developed a novel Missing Modality Transfer Learning (MMTL) algorithm capable of utilizing whatever imaging modalities are available for an MCI patient to diagnose the patient's likelihood of MCI due to AD. Furthermore, we integrated MMTL with radiomics steps including image processing, feature extraction, and feature screening, and a post-processing for uncertainty quantification (UQ), and developed a CAD system called "ADMultiImg" to assist clinical diagnosis of MCI due to AD using multi-modality images together with patient demographic and genetic information. Tested on ADNI date, our system can generate a diagnosis with high accuracy even for patients with only partially available image modalities (AUC=0.94), and therefore may have broad clinical utility.

An Investigation on the Status of Implementation of Communications and Information Management System (MCI) in Khorasan Razavi Hospitals.

Science.gov (United States)

Shojaei, Saeed; Farzianpour, Fereshteh; Arab, Mohammad; Rahimi Foroushani, Abbas

2015-09-02

The aim of this investigation is to determine the mean scores of the possibility of implementing the MCI standards in Khorasan Razavi hospitals, from the perspective of Managers, in order to provide a suitable model for evaluating and promoting the system. This was a Research and method (R&D) and Survey Research method, which is of the type of Cross- Sectional, descriptive-analytic Studies conducted in two steps in hospitals of Khorasan Razavi from July to December 2014. This study was approved by the Ethical Committee of Tehran University of Medical Sciences (TUMS) in 2013/6/10. About the nature and purpose of the study was explained to the participants. Were used to apply functional assessment, based on Accreditation Model. In order to collect data, two questionnaires were used, all of which were taken from the standards of MCI. The reliability and validity of the questionnaires were approved by experts.Cronbach's alphas for the questionnaires were obtained to be (0.95, 0.86), respectively. In order to analyze information, statistical analyses, including one way ANOVA, and Independent sample t-test were used. The mean scores of the possibility of implementing the MCI standards in Khorasan Razavi hospitals, were (51.6 and 12.27), respectively. According to half (43.8%) of managers, the MCI standards are applicable in hospitals of Khorasan Razavi; however, their application requires greater efforts by the hospitals.

A frequency domain global parameter estimation method for multiple reference frequency response measurements

Science.gov (United States)

Shih, C. Y.; Tsuei, Y. G.; Allemang, R. J.; Brown, D. L.

1988-10-01

A method of using the matrix Auto-Regressive Moving Average (ARMA) model in the Laplace domain for multiple-reference global parameter identification is presented. This method is particularly applicable to the area of modal analysis where high modal density exists. The method is also applicable when multiple reference frequency response functions are used to characterise linear systems. In order to facilitate the mathematical solution, the Forsythe orthogonal polynomial is used to reduce the ill-conditioning of the formulated equations and to decouple the normal matrix into two reduced matrix blocks. A Complex Mode Indicator Function (CMIF) is introduced, which can be used to determine the proper order of the rational polynomials.

Citation analysis of The Korean Journal of Internal Medicine from KoMCI, Web of Science, and Scopus.

Science.gov (United States)

Huh, Sun

2011-03-01

The Korean Journal of Internal Medicine (KJIM) is the international journal published in English by the Korean Association of Internal Medicine. To understand the position of the journal in three different databases, the citation indicators were elucidated. From databases such as Korean Medical Citation Index (KoMCI), Web of Science, and Scopus, citation indicators such as the impact factor, SCImago journal rank (SJR), or Hirsch Index were calculated according to the year and the results were drawn. The KJIM 2010 impact factor increased to 0.623 in Web of Science. That of year 2009 in KoMCI was a 0.149. The 2009 SJR in Scopus was 0.073, with a ranking of 27/72 (37.5%) in the category of internal medicine and 414/1,618 (25.6%) in the category of medicine, miscellaneous. The Hirsch Index from KoMCI, Web of Science and Scopus were 5, 14, and 16, respectively. The KJIM is now cited more by international researchers than Korean researchers, indicating that the content of the journal is now valued at the international level.

Domains of quality of life of people with profound multiple disabilities : The perspective of parents and direct support staff

NARCIS (Netherlands)

Petry, K; Maes, B; Vlaskamp, C

Background This study considered the general validity of the basic domains of quality of life that appear in theoretical models, in relation to people with profound multiple disabilities. The authors examined how parents and direct support staff operationalized these basic domains for people with

An efficient multiple exposure image fusion in JPEG domain

Science.gov (United States)

Hebbalaguppe, Ramya; Kakarala, Ramakrishna

2012-01-01

In this paper, we describe a method to fuse multiple images taken with varying exposure times in the JPEG domain. The proposed algorithm finds its application in HDR image acquisition and image stabilization for hand-held devices like mobile phones, music players with cameras, digital cameras etc. Image acquisition at low light typically results in blurry and noisy images for hand-held camera's. Altering camera settings like ISO sensitivity, exposure times and aperture for low light image capture results in noise amplification, motion blur and reduction of depth-of-field respectively. The purpose of fusing multiple exposures is to combine the sharp details of the shorter exposure images with high signal-to-noise-ratio (SNR) of the longer exposure images. The algorithm requires only a single pass over all images, making it efficient. It comprises of - sigmoidal boosting of shorter exposed images, image fusion, artifact removal and saturation detection. Algorithm does not need more memory than a single JPEG macro block to be kept in memory making it feasible to be implemented as the part of a digital cameras hardware image processing engine. The Artifact removal step reuses the JPEGs built-in frequency analysis and hence benefits from the considerable optimization and design experience that is available for JPEG.

On the practical modeling of conceptual overlap among multiple facets in ontology domain concepts (Mini-thesis)

OpenAIRE

Rodriguez-Castro, Benedicto; Glaser, Hugh; Carr, Leslie

2007-01-01

This report presents a study on the practical modelling of the conceptual overlap that might exist among the multiple facets that define a particular ontology domain concept. The notions of conceptual overlap and facet are defined, together with their relation to scenarios of multiple inheritance in ontology models. Starting from the notion of a value partition, a terminology of ontology modelling constructs is introduced that allows the characterization of two types of conceptual overlap wit...

An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

Energy Technology Data Exchange (ETDEWEB)

Wong, Jaslyn E. M. M. [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Midtgaard, Søren Roi [University of Copenhagen, Universitetsparken 5, 2100 Copenhagen (Denmark); Gysel, Kira [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark); Thygesen, Mikkel B.; Sørensen, Kasper K.; Jensen, Knud J. [University of Copenhagen, Thorvaldsensvej 40, 1871 Frederiksberg C (Denmark); Stougaard, Jens; Thirup, Søren; Blaise, Mickaël, E-mail: mickael.blaise@cpbs.cnrs.fr [Aarhus University, Gustav Wieds Vej 10C, 8000 Aarhus (Denmark)

2015-03-01

The crystal and solution structures of the T. thermophilus NlpC/P60 d, l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan. LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of the Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.

Assessment of PET & ASL metabolism in the hippocampal subfields of MCI and AD using simultaneous PET-MR

Energy Technology Data Exchange (ETDEWEB)

Goubran, Maged; Douglas, David; Chao, Steven; Quon, Andrew; Tripathi, Pragya; Holley, Dawn; Vasanawala, Minal; Zaharchuk, Greg; Zeineh, Michael [Stanford University (United States)

2015-05-18

Alzheimer’s disease (AD) has been reported to show decreased metabolic activity in the hippocampus using FDG PET-MR. Histological data suggests that the hippocampal subfields are selectively affected in AD. Given the simultaneous imaging nature of integrated PET-MR scanners and the multimodal capabilities of PET-MR, our purpose here is to assess FDG activity, as well as ASL perfusion in the subfields of MCI and AD patients. 10 consecutive subjects were recruited for this study 3 MCI, 3 AD patients and 4 age-matched controls. The scanning was performed on a simultaneous 3T PET/MR scanner. To delineate the hippocampal subfields, automatic segmentation of hippocampal subfields (ASHS) was employed. Static FDG-PET series were reconstructed for analysis at 45-75 min for all subjects. All imaging sequences were automatically registered to the oblique coronal T2-weighted images (segmentation space). PET standardized uptake values (SUV) in the hippocampal subfields were normalized by the pons. FDG PET metabolism was reduced significantly in AD, as well as MCI patients as compared to controls, with the highest effect demonstrated in the CA3/DG and CA1/2 (p = 0.047, subfields. Patients (MCI and AD combined) had decreased metabolism as compared to controls in CA1/2 and significantly smaller volumes the Subiculum. When assessing CBF across groups, a significant decrease in CBF was found in the Subiculum. Our preliminary results demonstrate that PET-MRI may potentially be a sensitive biomarker and tool for early diagnosis of AD. They also confirm the importance of assessing metabolic and structural changes of neurodegenerative diseases at the subfield level.

Objective Ratings of Relationship Skills across Multiple Domains as Predictors of Marital Satisfaction Trajectories

OpenAIRE

Lawrence, Erika; Pederson, Ashley; Bunde, Mali; Barry, Robin A.; Brock, Rebecca L.; Fazio, Emily; Mulryan, Lorin; Hunt, Sara; Madsen, Lisa; Dzankovic, Sandra

2008-01-01

Expanding upon social-learning and vulnerability-stress-adaptation approaches to marriage, the impact of multiple dyadic behaviors on marital satisfaction trajectories was examined in 101 couples. Semi-structured interviews were administered separately to husbands and wives at 3 months of marriage. Interviewers generated objective ratings for five domains: emotional closeness/intimacy, sexual intimacy/sensuality, interspousal support, decision-making/relational control, and communication/conf...

An Examination of Multiple Intelligence Domains and Learning Styles of Pre-Service Mathematics Teachers: Their Reflections on Mathematics Education

Science.gov (United States)

Ozgen, Kemal; Tataroglu, Berna; Alkan, Huseyin

2011-01-01

The present study aims to identify pre-service mathematics teachers' multiple intelligence domains and learning style profiles, and to establish relationships between them. Employing the survey model, the study was conducted with the participation of 243 pre-service mathematics teachers. The study used the "multiple intelligence domains…

Intraindividual variability across cognitive tasks as a potential marker for prodromal Alzheimer’s disease

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Andrea Maria Kälin

2014-07-01

Full Text Available Recent studies have shown that increased cognitive intraindividual variability (IIV across accuracy scores from tests representing different cognitive domains (across-domain IIV might indicate prodromal Alzheimer’s disease (AD. Although IIV has been proposed to index cognitive control processes, IIV across accuracy scores from cognitive control tasks (within-domain IIV has not been examined in healthy controls subjects (HCS, mild cognitive impairment (MCI and AD patients in a single comparative study. This study examines the discriminative properties of within-domain IIV, and across-domain IIV in 149 HCS, 31 MCI and 26 AD. Three tasks representing different cognitive domains were identified to calculate across-domain IIV. Three other tasks representing cognitive control were identified to calculate within-domain IIV. The intraindividual standard deviation (ISD was calculated across accuracy scores. To compare IIV between groups, ANCOVAs with the covariates age, gender, education, and mean performance were computed. IIV scores in general were higher in AD vs. HCS (p< 0.01. Only across-domain IIV was higher in AD vs. MCI (p=0.001, and only within-domain IIV was higher in MCI vs. HCS (p=0.05. Within-domain IIV may constitute a cognitive marker for the detection of prodromal AD at the MCI stage, whereas across-domain IIV may detect beginning AD at the MCI stage.

Serial position effects are sensitive predictors of conversion from MCI to Alzheimer's disease dementia.

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Egli, Simone C; Beck, Irene R; Berres, Manfred; Foldi, Nancy S; Monsch, Andreas U; Sollberger, Marc

2014-10-01

It is unclear whether the predictive strength of established cognitive variables for progression to Alzheimer's disease (AD) dementia from mild cognitive impairment (MCI) varies depending on time to conversion. We investigated which cognitive variables were best predictors, and which of these variables remained predictive for patients with longer times to conversion. Seventy-five participants with MCI were assessed on measures of learning, memory, language, and executive function. Relative predictive strengths of these measures were analyzed using Cox regression models. Measures of word-list position-namely, serial position scores-together with Short Delay Free Recall of word-list learning best predicted conversion to AD dementia. However, only serial position scores predicted those participants with longer time to conversion. Results emphasize that the predictive strength of cognitive variables varies depending on time to conversion to dementia. Moreover, finer measures of learning captured by serial position scores were the most sensitive predictors of AD dementia. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

N-acetylaspartate, choline and myoinositol concentration changes in MR spectroscopy (1H MRS) of hippocampal formation in patients with mild cognitive impairment (MCI) - preliminary study

International Nuclear Information System (INIS)

Pawlowska, A.; Cwikla, J.; Walecki, J.; Gabryelewicz, T.; Barcikowska, M.

2004-01-01

Cognitive and memory impairment are very common problems in elderly patients. Mild cognitive impairment (MCI) is known as a transitional clinical state between normal ('successful') aging and dementia. In some cases MCI may be a precursor to Alzheimer's disease (AD). Early neuronal loss and metabolic changes have been documented in previous studies in AD patients in some 'strategic ' regions of the brain, mainly in hippocampal formation. Our goal was to determine whether there are statistically significant changes in hippocampal N-acetylaspartate, choline and myoinositol levels obtained by single-voxel spectroscopy in MCI patients and normal aging and to evaluate its clinical diagnostic utility. 30 patients with MCI and 15 cognitively normal elderly subjects underwent proton MR spectroscopy at 1.5 T system. MR spectra were obtained from anterior and posterior part of hippocampal formation bilaterally, using the point-resolved spectroscopy sequence. Metabolite ratios of NAA/H 2 O, Cho/H 2 O and mI/H 2 O were calculated from the peak height measurements. Relative to the control group, patients with MCI demonstrated elevated mI/H 2 O and Cho/H 2 O ratios in both hippocampal formations. The most significant increase was observed in mI/H 2 O ratio in anterior part of left hippocampus and in Cho/H 2 O ratio in posterior part of right hippocampus, in MCI patients vs.cognitively normal elderly. There were no significant differences between mean NAA/H 2 O ratios measured in hippocampal formation in both groups. Proton MRS may be used as valuable additional tool in the evaluation of regional metabolic changes in patients with MCI. Increase of mI and Cho levels in hippocampal formation may be an early sign of cognitive impairment in elderly subjects that can be measured using MRS. (author)

Energy-Aware Routing in Multiple Domains Software-Defined Networks

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Adriana FERNÁNDEZ-FERNÁNDEZ

2016-12-01

Full Text Available The growing energy consumption of communication networks has attracted the attention of the networking researchers in the last decade. In this context, the new architecture of Software-Defined Networks (SDN allows a flexible programmability, suitable for the power-consumption optimization problem. In this paper we address the issue of designing a novel distributed routing algorithm that optimizes the power consumption in large scale SDN with multiple domains. The solution proposed, called DEAR (Distributed Energy-Aware Routing, tackles the problem of minimizing the number of links that can be used to satisfy a given data traffic demand under performance constraints such as control traffic delay and link utilization. To this end, we present a complete formulation of the optimization problem that considers routing requirements for control and data plane communications. Simulation results confirm that the proposed solution enables the achievement of significant energy savings.

Frequent mild cognitive deficits in several functional domains in elderly patients with heart failure without known cognitive disorders.

Science.gov (United States)

Nordlund, Arto; Berggren, Jens; Holmström, Alexandra; Fu, Michael; Wallin, Anders

2015-09-01

The objective of the present study was to investigate whether mild cognitive deficits are present in patients with heart failure (HF) despite absence of any known cognitive disorder. A well defined group of patients (n = 40) with heart failure completed a cognitive screening check list, a depression screening questionnaire, and a battery consisting of neuropsychological tests assessing 5 different cognitive domains: speed/attention, episodic memory, visuospatial functions, language, and executive functions. The neuropsychological results were compared with those from a group of healthy control subjects (n = 41). The patients with HF displayed cognitive impairment compared with the control group within the domains speed and attention, episodic memory, visuospatial functions, and language. Among them, 34 HF patients (85%) could be classified with mild cognitive impairment (MCI), the majority as nonamnestic MCI, ie, with no memory impairment. Considering the high occurrence of mild cognitive deficits among HF patients without known cognitive disorders, closer attention should be paid to their self-care and compliance. Inadequate self-care and compliance could lead to more frequent hospitalizations. Furthermore, the HF patients may be at increased risk of dementia. Copyright © 2015 Elsevier Inc. All rights reserved.

18F PET with florbetaben for the early diagnosis of Alzheimer's disease dementia and other dementias in people with mild cognitive impairment (MCI).

Science.gov (United States)

Martínez, Gabriel; Vernooij, Robin Wm; Fuentes Padilla, Paulina; Zamora, Javier; Flicker, Leon; Bonfill Cosp, Xavier

2017-11-22

relevant studies and systematic reviews, and performed citation tracking using the Science Citation Index to identify any additional relevant studies. No language or date restrictions were applied to electronic searches. We included studies that had prospectively defined cohorts with any accepted definition of MCI at time of performing the test and the use of 18 F-florbetaben scan to evaluate the DTA of the progression from MCI to ADD or other forms of dementia. In addition, we only selected studies that applied a reference standard for Alzheimer's dementia diagnosis, for example, the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) or Diagnostic and Statistical Manual of Mental Disorders-IV (DSM-IV) criteria. We screened all titles and abstracts identified in electronic-database searches. Two review authors independently selected studies for inclusion and extracted data to create two-by-two tables, showing the binary test results cross-classified with the binary reference standard. We used these data to calculate sensitivities, specificities, and their 95% confidence intervals. Two independent assessors performed quality assessment using the QUADAS-2 tool plus some additional items to assess the methodological quality of the included studies. Progression from MCI to ADD, any other form of dementia, and any form of dementia was evaluated in one study (Ong 2015). It reported data on 45 participants at four years of follow-up; 21 participants met NINCDS-ADRDA criteria for Alzheimer's disease dementia at four years of follow-up, the proportion converting to ADD was 47% of the 45 participants, and 11% of the 45 participants met criteria for other types of dementias (three cases of FrontoTemporal Dementia (FTD), one of Dementia with Lewy body (DLB), and one of Progressive Supranuclear Palsy (PSP)). We considered the study to be at high risk of bias in the domains of the

A Logic for Inclusion of Administrative Domains and Administrators in Multi-domain Authorization

Science.gov (United States)

Iranmanesh, Zeinab; Amini, Morteza; Jalili, Rasool

Authorization policies for an administrative domain or a composition of multiple domains in multi-domain environments are determined by either one administrator or multiple administrators' cooperation. Several logic-based models for multi-domain environments' authorization have been proposed; however, they have not considered administrators and administrative domains in policies' representation. In this paper, we propose the syntax, proof theory, and semantics of a logic for multi-domain authorization policies including administrators and administrative domains. Considering administrators in policies provides the possibility of presenting composite administration having applicability in many collaborative applications. Indeed, administrators and administrative domains stated in policies can be used in authorization. The presented logic is based on modal logic and utilizes two calculi named the calculus of administrative domains and the calculus of administrators. It is also proved that the logic is sound. A case study is presented signifying the logic application in practical projects.

Structural and functional analysis of multi-interface domains.

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Liang Zhao

Full Text Available A multi-interface domain is a domain that can shape multiple and distinctive binding sites to contact with many other domains, forming a hub in domain-domain interaction networks. The functions played by the multiple interfaces are usually different, but there is no strict bijection between the functions and interfaces as some subsets of the interfaces play the same function. This work applies graph theory and algorithms to discover fingerprints for the multiple interfaces of a domain and to establish associations between the interfaces and functions, based on a huge set of multi-interface proteins from PDB. We found that about 40% of proteins have the multi-interface property, however the involved multi-interface domains account for only a tiny fraction (1.8% of the total number of domains. The interfaces of these domains are distinguishable in terms of their fingerprints, indicating the functional specificity of the multiple interfaces in a domain. Furthermore, we observed that both cooperative and distinctive structural patterns, which will be useful for protein engineering, exist in the multiple interfaces of a domain.

[Diagnostic value of neuropsychological tests in mild cognitive impairment comorbid with Parkinson's disease].

Science.gov (United States)

Laskowska, Ilona; Koczorowski, Andrzej; Koziorowski, Dariusz; Gawryś, Ludwika

2014-01-01

Mild cognitive impairment (MCI) is present in on average one-fourth of Parkinson's disease (PD) patients with no dementia diagnosis. Only recently has PD-MCI been treated as a new diagnostic entity. In 2012, unified criteria were adopted which allow both diagnosing MCI in Parkinson's disease (PD-MCI) and further classification taking into account the profile of cognitive dysfunctions and the probability of evolution towards dementia. The diagnostic criteria were presented in the form of stipulations and guidelines assuming that diagnostic process is based on the neuropsychological assessment of the patient. The notion of MCI had been borrowed and for a couple of years had been relying on definitions developed in relation to Alzheimer's disease. For the first time, in the proposed criteria memory dysfunction is not the basis of classification. Only two categories of dysfunctions have been retained, single-domain and multiple-domain. Whether the adopted criteria will contribute to an accurate diagnosis of cognitive dysfunctions and PD-specific dementing processes remains an open question. In spite of some limitations, the presented criteria can certainly improve the efficacy of monitoring the patient's state at the same time allowing the hope for an appropriate therapy and a higher quality of life. Moreover, the unification of diagnostic criteria will be crucial in assessing usefulness ofneuropsychological test instruments as a basic method of investigating neurodegenerative processes not only in PD.

The Memory Aid study: protocol for a randomized controlled clinical trial evaluating the effect of computer-based working memory training in elderly patients with mild cognitive impairment (MCI).

Science.gov (United States)

Flak, Marianne M; Hernes, Susanne S; Chang, Linda; Ernst, Thomas; Douet, Vanessa; Skranes, Jon; Løhaugen, Gro C C

2014-05-03

Mild cognitive impairment (MCI) is a condition characterized by memory problems that are more severe than the normal cognitive changes due to aging, but less severe than dementia. Reduced working memory (WM) is regarded as one of the core symptoms of an MCI condition. Recent studies have indicated that WM can be improved through computer-based training. The objective of this study is to evaluate if WM training is effective in improving cognitive function in elderly patients with MCI, and if cognitive training induces structural changes in the white and gray matter of the brain, as assessed by structural MRI. The proposed study is a blinded, randomized, controlled trail that will include 90 elderly patients diagnosed with MCI at a hospital-based memory clinic. The participants will be randomized to either a training program or a placebo version of the program. The intervention is computerized WM training performed for 45 minutes of 25 sessions over 5 weeks. The placebo version is identical in duration but is non-adaptive in the difficulty level of the tasks. Neuropsychological assessment and structural MRI will be performed before and 1 month after training, and at a 5-month folllow-up. If computer-based training results in positive changes to memory functions in patients with MCI this may represent a new, cost-effective treatment for MCI. Secondly, evaluation of any training-induced structural changes to gray or white matter will improve the current understanding of the mechanisms behind effective cognitive interventions in patients with MCI. ClinicalTrials.gov NCT01991405. November 18, 2013.

Identificação do gene mcyA em florações naturais de Radiocystis fernandoi, em um tributário do reservatório de Rosana, Brasil = Identification of the mcyA gene in natural blooms of Radiocystis fernandoi from a tributary of the Rosana reservoir, Brazil

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Iraúza Arroteia Fonseca

2011-07-01

Full Text Available As cianobactérias são conhecidamente produtoras de toxinas. Dentro de uma mesma espécie, podemos encontrar variedades tóxicas e não-tóxicas, impossíveis de diferenciação apenas pela morfologia. A principal toxina produzida pelas cianobactérias é a microcistina. Esta proteína é biossintetizada por um grupo de genes conhecidos como mcy. A detecção destes genes a partir de PCR permite a distinção das variedades tóxicas e nãotóxicas. Desse modo, o objetivo desse trabalho foi investigar a ocorrência de florações produtoras de toxinas em um rio tributário do reservatório de Rosana, via amplificação do gene mcyA por PCR. Foram coletadas duas amostras de água da subsuperfície. As duas amostras coletadas no rio do Corvo foram dominadas pela espécie Radiocystis fernandoi e apresentaram resultados positivos para a presença do gene mcyA, confirmando o potencial tóxico dessa espécie. Os resultados representam alerta sobre a qualidade da água do rio do Corvo. A técnica PCR foi eficiente para a rápida detecção de cianobactérias produtoras detoxinas, inclusive podendo ser utilizada antes mesmo do agravamento das condições ambientais pela produção de toxinas, além de apresentar baixo custo.Cyanobacterias are known as toxin producers. Within the same species, toxic and non-toxic varieties can be found and it is impossible to differentiate them only by morphology. The most important toxinproduced by cyanobacteria is microcystin. This protein is synthesized by a cluster of genes known as mcy. The detection of these genes by PCR allows the differentiation of the producing toxin strain from the non-producing toxin strain. Thus, the goal of this work was to investigate the occurrence of toxigenic blooms of cyanobacteria in the Corvo River through PCR amplification of mcyA gene. For this, two samples of blooms of cyanobacteria were collected in Corvo River. Both samples were dominated by Radiocystis fernandoi and presented

Mapping brain morphological and functional conversion patterns in amnestic MCI: a voxel-based MRI and FDG-PET study

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Morbelli, Silvia [University of Genoa, Nuclear Medicine Unit, Department of Internal Medicine, Genoa (Italy); Piccardo, Arnoldo; Villavecchia, Giampiero [Galliera Hospital, Nuclear Medicine Unit, Department of Radiology, Genoa (Italy); Dessi, Barbara; Brugnolo, Andrea; Rodriguez, Guido; Nobili, Flavio [University of Genoa, Clinical Neurophysiology Unit, Department of Neurosciences, Ophthalmology and Genetics, Genoa (Italy); Piccini, Alessandra [Cell Biology Unit, National Cancer Research Institute, Genoa (Italy); Caroli, Anna [LENITEM - Laboratory of Epidemiology Neuroimaging and Telemedicine, Brescia (Italy); Mario Negri Institute, Medical Imaging Unit, Biomedical Engineering Department, Bergamo (Italy); Frisoni, Giovanni [LENITEM - Laboratory of Epidemiology Neuroimaging and Telemedicine, Brescia (Italy)

2010-01-15

To reveal the morphological and functional substrates of memory impairment and conversion to Alzheimer disease (AD) from the stage of amnestic mild cognitive impairment (aMCI). Brain MRI and FDG-PET were performed in 20 patients with aMCI and 12 controls at baseline. During a mean follow-up of about 2 years, 9 patients developed AD (converters), and 11 did not (nonconverters). All images were processed with SPM2. FDG-PET and segmented grey matter (GM) images were compared in: (1) converters versus controls, (2) nonconverters versus controls, and (3) converters versus nonconverters. As compared to controls, converters showed lower GM density in the left parahippocampal gyrus and both thalami, and hypometabolism in the precuneus, posterior cingulate and superior parietal lobule in the left hemisphere. Hypometabolism was found in nonconverters as compared to controls in the left precuneus and posterior cingulated gyrus. As compared to nonconverters, converters showed significant hypometabolism in the left middle and superior temporal gyri. The discordant topography between atrophy and hypometabolism reported in AD is already present at the aMCI stage. Posterior cingulate-precuneus hypometabolism seemed to be an early sign of memory deficit, whereas hypometabolism in the left temporal cortex marked the conversion to AD. (orig.)

Self-administered Gerocognitive Examination (SAGE): a brief cognitive assessment Instrument for mild cognitive impairment (MCI) and early dementia.

Science.gov (United States)

Scharre, Douglas W; Chang, Shu-Ing; Murden, Robert A; Lamb, James; Beversdorf, David Q; Kataki, Maria; Nagaraja, Haikady N; Bornstein, Robert A

2010-01-01

To develop a self-administered cognitive assessment instrument to facilitate the screening of mild cognitive impairment (MCI) and early dementia and determine its association with gold standard clinical assessments including neuropsychologic evaluation. Adults aged above 59 years with sufficient vision and English literacy were recruited from geriatric and memory disorder clinics, educational talks, independent living facilities, senior centers, and memory screens. After Self-administered Gerocognitive Examination (SAGE) screening, subjects were randomly selected to complete a clinical evaluation, neurologic examination, neuropsychologic battery, functional assessment, and mini-mental state examination (MMSE). Subjects were identified as dementia, MCI, or normal based on standard clinical criteria and neuropsychologic testing. Two hundred fifty-four participants took the SAGE screen and 63 subjects completed the extensive evaluation (21 normal, 21 MCI, and 21 dementia subjects). Spearman rank correlation between SAGE and neuropsychologic battery was 0.84 (0.76 for MMSE). SAGE receiver operating characteristics on the basis of clinical diagnosis showed 95% specificity (90% for MMSE) and 79% sensitivity (71% for MMSE) in detecting those with cognitive impairment from normal subjects. This study suggests that SAGE is a reliable instrument for detecting cognitive impairment and compares favorably with the MMSE. The self-administered feature may promote cognitive testing by busy clinicians prompting earlier diagnosis and treatment.

Evaluation of radioiodine therapy with fixed doses of 10 and 15 mCi in patients with Graves disease

International Nuclear Information System (INIS)

Canadas, Viviane; Vilar, Lucio; Moura, Eliane; Brito, Ana; Castellar, Enio

2007-01-01

The treatment options for the hyperthyroidism of Graves' disease are antithyroid drugs, surgery and radioiodine, none of which is considered ideal, as they do not act directly on the etiopathogenesis of the disease. Radioiodine has been increasingly used as the treatment of choice because it is a safe and definitive therapy whose administration is very easy. Some authors prefer to administer higher doses in order to deliberately induce hypothyroidism, while others recommend lower doses that result in a lower incidence of hypothyroidism and a greater incidence of euthyroidism. There is no consensus for the optimal regimen of fixed doses to be used and this is the main focus of the present study, where doses of 10 and 15 mCi of 131 I were compared. Among the 164 patients analyzed, 61 (37.2%) were submitted to 10 mCi and 103 (62.8%) to 15 mCi. In the longitudinal analysis it was observed that remission of the hyperthyroidism was statistically different in the sixth month (p 131 I brought about a similar remission of the hyperthyroidism after 12 months of treatment. Moreover, the remission rate of the hyperthyroidism had no association with age, sex or previous therapy with antithyroid drugs. (author)

Mapping brain morphological and functional conversion patterns in amnestic MCI: a voxel-based MRI and FDG-PET study

International Nuclear Information System (INIS)

Morbelli, Silvia; Piccardo, Arnoldo; Villavecchia, Giampiero; Dessi, Barbara; Brugnolo, Andrea; Rodriguez, Guido; Nobili, Flavio; Piccini, Alessandra; Caroli, Anna; Frisoni, Giovanni

2010-01-01

To reveal the morphological and functional substrates of memory impairment and conversion to Alzheimer disease (AD) from the stage of amnestic mild cognitive impairment (aMCI). Brain MRI and FDG-PET were performed in 20 patients with aMCI and 12 controls at baseline. During a mean follow-up of about 2 years, 9 patients developed AD (converters), and 11 did not (nonconverters). All images were processed with SPM2. FDG-PET and segmented grey matter (GM) images were compared in: (1) converters versus controls, (2) nonconverters versus controls, and (3) converters versus nonconverters. As compared to controls, converters showed lower GM density in the left parahippocampal gyrus and both thalami, and hypometabolism in the precuneus, posterior cingulate and superior parietal lobule in the left hemisphere. Hypometabolism was found in nonconverters as compared to controls in the left precuneus and posterior cingulated gyrus. As compared to nonconverters, converters showed significant hypometabolism in the left middle and superior temporal gyri. The discordant topography between atrophy and hypometabolism reported in AD is already present at the aMCI stage. Posterior cingulate-precuneus hypometabolism seemed to be an early sign of memory deficit, whereas hypometabolism in the left temporal cortex marked the conversion to AD. (orig.)

Neural Dynamics of Multiple Object Processing in Mild Cognitive Impairment and Alzheimer's Disease: Future Early Diagnostic Biomarkers?

Science.gov (United States)

Bagattini, Chiara; Mazza, Veronica; Panizza, Laura; Ferrari, Clarissa; Bonomini, Cristina; Brignani, Debora

2017-01-01

The aim of this study was to investigate the behavioral and electrophysiological dynamics of multiple object processing (MOP) in mild cognitive impairment (MCI) and Alzheimer's disease (AD), and to test whether its neural signatures may represent reliable diagnostic biomarkers. Behavioral performance and event-related potentials [N2pc and contralateral delay activity (CDA)] were measured in AD, MCI, and healthy controls during a MOP task, which consisted in enumerating a variable number of targets presented among distractors. AD patients showed an overall decline in accuracy for both small and large target quantities, whereas in MCI patients, only enumeration of large quantities was impaired. N2pc, a neural marker of attentive individuation, was spared in both AD and MCI patients. In contrast, CDA, which indexes visual short term memory abilities, was altered in both groups of patients, with a non-linear pattern of amplitude modulation along the continuum of the disease: a reduction in AD and an increase in MCI. These results indicate that AD pathology shows a progressive decline in MOP, which is associated to the decay of visual short-term memory mechanisms. Crucially, CDA may be considered as a useful neural signature both to distinguish between healthy and pathological aging and to characterize the different stages along the AD continuum, possibly becoming a reliable candidate for an early diagnostic biomarker of AD pathology.

Integration and relative value of biomarkers for prediction of MCI to AD progression: Spatial patterns of brain atrophy, cognitive scores, APOE genotype and CSF biomarkers

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Xiao Da

2014-01-01

Full Text Available This study evaluates the individual, as well as relative and joint value of indices obtained from magnetic resonance imaging (MRI patterns of brain atrophy (quantified by the SPARE-AD index, cerebrospinal fluid (CSF biomarkers, APOE genotype, and cognitive performance (ADAS-Cog in progression from mild cognitive impairment (MCI to Alzheimer's disease (AD within a variable follow-up period up to 6 years, using data from the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI-1. SPARE-AD was first established as a highly sensitive and specific MRI-marker of AD vs. cognitively normal (CN subjects (AUC = 0.98. Baseline predictive values of all aforementioned indices were then compared using survival analysis on 381 MCI subjects. SPARE-AD and ADAS-Cog were found to have similar predictive value, and their combination was significantly better than their individual performance. APOE genotype did not significantly improve prediction, although the combination of SPARE-AD, ADAS-Cog and APOE ε4 provided the highest hazard ratio estimates of 17.8 (last vs. first quartile. In a subset of 192 MCI patients who also had CSF biomarkers, the addition of Aβ1–42, t-tau, and p-tau181p to the previous model did not improve predictive value significantly over SPARE-AD and ADAS-Cog combined. Importantly, in amyloid-negative patients with MCI, SPARE-AD had high predictive power of clinical progression. Our findings suggest that SPARE-AD and ADAS-Cog in combination offer the highest predictive power of conversion from MCI to AD, which is improved, albeit not significantly, by APOE genotype. The finding that SPARE-AD in amyloid-negative MCI patients was predictive of clinical progression is not expected under the amyloid hypothesis and merits further investigation.

18F-FDG PET diagnostic and prognostic patterns do not overlap in Alzheimer's disease (AD) patients at the mild cognitive impairment (MCI) stage

International Nuclear Information System (INIS)

Morbelli, Silvia; Bauckneht, Matteo; Buschiazzo, Ambra; Nieri, Alberto; Sambuceti, Gianmario; Pagani, Marco; De Carli, Fabrizio

2017-01-01

We aimed to identify the cortical regions where hypometabolism can predict the speed of conversion to dementia in mild cognitive impairment due to Alzheimer's disease (MCI-AD). We selected from the clinical database of our tertiary center memory clinic, eighty-two consecutive MCI-AD that underwent 18F-fluorodeoxyglucose (FDG) PET at baseline during the first diagnostic work-up and were followed up at least until their clinical conversion to AD dementia. The whole group of MCI-AD was compared in SPM8 with a group of age-matched healthy controls (CTR) to verify the presence of AD diagnostic-pattern; then the correlation between conversion time and brain metabolism was assessed to identify the prognostic-pattern. Significance threshold was set at p < 0.05 False-Discovery-Rate (FDR) corrected at peak and at cluster level. Each MCI-AD was then compared with CTR by means of a SPM single-subject analysis and grouped according to presence of AD diagnostic-pattern and prognostic-pattern. Kaplan-Meier-analysis was used to evaluate if diagnostic- and/or prognostic-patterns can predict speed of conversion to dementia. Diagnostic-pattern corresponded to typical posterior hypometabolism (BA 7, 18, 19, 30, 31 and 40) and did not correlate with time to conversion, which was instead correlated with metabolic levels in right middle and inferior temporal gyri as well as in the fusiform gyrus (prognostic-pattern, BA 20, 21 and 38). At Kaplan-Meier analysis, patients with hypometabolism in the prognostic pattern converted to AD-dementia significantly earlier than patients not showing significant hypometabolism in the right middle and inferior temporal cortex (9 versus 19 months; Log rank p < 0.02, Breslow test: p < 0.003, Tarone-Ware test: p < 0.007). The present findings support the role of FDG PET as a robust progression biomarker even in a naturalist population of MCI-AD. However, not the AD-typical diagnostic-pattern in posterior regions but the middle and inferior temporal

18F-FDG PET diagnostic and prognostic patterns do not overlap in Alzheimer's disease (AD) patients at the mild cognitive impairment (MCI) stage

Energy Technology Data Exchange (ETDEWEB)

Morbelli, Silvia; Bauckneht, Matteo; Buschiazzo, Ambra; Nieri, Alberto; Sambuceti, Gianmario [Genoa Univ. (Italy). Dept. of Health Sciences; IRCCS AOU San Martino-IST, Genoa (Italy). Nuclear Medicine Unit; Arnaldi, Dario; Picco, Agnese; Pardini, Matteo; Brugnolo, Andrea; Girtler, Nicola; Nobili, Flavio [Genoa Univ. (Italy). Clinical Neurology, Department of Neuroscience (DINOGMI); IRCCS AOU San Martino-IST, Genoa (Italy); Pagani, Marco [Institute of Cognitive Sciences and Technologies, Rome (Italy); Karolinska Hospital, Stockholm (Sweden). Department of Nuclear Medicine; Chincarini, Andrea [Istituto Nazionale di Fisica Nucleare, Genoa (Italy); De Carli, Fabrizio [National Research Council, Genoa (Italy). Institute of Bioimaging and Molecular Physiology

2017-11-15

We aimed to identify the cortical regions where hypometabolism can predict the speed of conversion to dementia in mild cognitive impairment due to Alzheimer's disease (MCI-AD). We selected from the clinical database of our tertiary center memory clinic, eighty-two consecutive MCI-AD that underwent 18F-fluorodeoxyglucose (FDG) PET at baseline during the first diagnostic work-up and were followed up at least until their clinical conversion to AD dementia. The whole group of MCI-AD was compared in SPM8 with a group of age-matched healthy controls (CTR) to verify the presence of AD diagnostic-pattern; then the correlation between conversion time and brain metabolism was assessed to identify the prognostic-pattern. Significance threshold was set at p < 0.05 False-Discovery-Rate (FDR) corrected at peak and at cluster level. Each MCI-AD was then compared with CTR by means of a SPM single-subject analysis and grouped according to presence of AD diagnostic-pattern and prognostic-pattern. Kaplan-Meier-analysis was used to evaluate if diagnostic- and/or prognostic-patterns can predict speed of conversion to dementia. Diagnostic-pattern corresponded to typical posterior hypometabolism (BA 7, 18, 19, 30, 31 and 40) and did not correlate with time to conversion, which was instead correlated with metabolic levels in right middle and inferior temporal gyri as well as in the fusiform gyrus (prognostic-pattern, BA 20, 21 and 38). At Kaplan-Meier analysis, patients with hypometabolism in the prognostic pattern converted to AD-dementia significantly earlier than patients not showing significant hypometabolism in the right middle and inferior temporal cortex (9 versus 19 months; Log rank p < 0.02, Breslow test: p < 0.003, Tarone-Ware test: p < 0.007). The present findings support the role of FDG PET as a robust progression biomarker even in a naturalist population of MCI-AD. However, not the AD-typical diagnostic-pattern in posterior regions but the middle and inferior temporal

The YARHG domain: an extracellular domain in search of a function.

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Penny Coggill

Full Text Available We have identified a new bacterial protein domain that we hypothesise binds to peptidoglycan. This domain is called the YARHG domain after the most highly conserved sequence-segment. The domain is found in the extracellular space and is likely to be composed of four alpha-helices. The domain is found associated with protein kinase domains, suggesting it is associated with signalling in some bacteria. The domain is also found associated with three different families of peptidases. The large number of different domains that are found associated with YARHG suggests that it is a useful functional module that nature has recombined multiple times.

Selective potentiation of noradrenaline in the guinea-pig vas deferens by 2-(4-methylaminobutoxy) diphenylmethane hydrochloride (MCI-2016), a new psychotropic drug.

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Ohizumi, Y.; Takahashi, M.; Tobe, A.

1982-01-01

In the isolated vas deferens of the guinea-pig, the effects of 2-(4-methylaminobutoxy) diphenylmethane hydrochloride (MCI-2016), a new psychotropic drug, on the contractile response to various agonists or transmural electrical stimulation and on the release of noradrenaline (NA) from the tissue were examined and compared with cocaine. MCI-2016 (3 X 10(-6)M) and cocaine (3 X 10(-5)M) produced a leftward shift (15 and 20 times, respectively) of the dose-response curves for the contractile effec...

Evaluation of treatment with 15 mCi of 131I to patients bearing toxic diffuse goiter (graves disease)

International Nuclear Information System (INIS)

Filho, J.A.; Silva, J.M. Ferreira da; Santoro, C.

2008-01-01

Full text: The multiple interferences of the physical and social environment on the people, represented especially for the lack of iodine, the basic chemical element for good functioning of the thyroid, in interior or raised regions; in situations of nutritional deficiency or excess of that chemical element absorbed through foods and or drugs; by stress and inadequate feeding to which they are submitted, when facing assumed social responsibilities; for the rural exodus in search of new chances in the great cities; and especially, the women, for the consequences of the continuous use of contraceptives; for greater sensitivity to the humoral and tumoral answers etc., if it becomes the greater target of the thyroid disease called Toxic Diffuse Goiter or Graves disease, as is verified in this report, the existence of about 4 women for each 1 man. However, the implemented sanitary actions for the treatment that such complex diseases, demand, are not satisfactory. The applied doses, on average, are not satisfying the necessities, according to the study carried out with 180 patients (38 males and 142 females), with an average age of (43.6 ± 12.6) years, varying from 15 to 70 years; an average thyroid mass of (37.4 ± 19.5) g, varying from 19.0 to 89.3 g; an average 24-hour uptake of 131 I of (53.6 ± 20.3) %, varying from 20.5 88.1 %; that they had been submitted to in average radiotherapeutic activity of (15.0 ± 1.4) mCi, varying from 12 to 20 mCi; where the output was (41.1 ± 15.6) % and the rate of desistance reached (52.4 ± 15.3) %. A retrospective study on the radiotherapeutic efficiency, covering dozens of treatments and thousands of patients from dozens of countries, in physical, clinical and biokinetic situations of iodine uptake by he thyroid, on average, similar to ours showed that the most efficient average dose, compared with our averages of dosimetric parameters, was about 30.2-34.5 mCi, that is, 2.0-2.3 times bigger than that the applied here. The data

Effects of Tai Chi on Cognition and Fall Risk in Older Adults with Mild Cognitive Impairment: A Randomized Controlled Trial.

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Sungkarat, Somporn; Boripuntakul, Sirinun; Chattipakorn, Nipon; Watcharasaksilp, Kanokwan; Lord, Stephen R

2017-04-01

To examine whether combined center- and home-based Tai Chi training can improve cognitive ability and reduce physiological fall risk in older adults with amnestic mild cognitive impairment (a-MCI). Randomized controlled trial. Chiang Mai, Thailand. Adults aged 60 and older who met Petersen's criteria for multiple-domain a-MCI (N = 66). Three weeks center-based and 12 weeks home-based Tai Chi (50 minutes per session, 3 times per week). Cognitive tests, including Logical Memory (LM) delayed recall, Block Design, Digit Span forward and backward, and Trail-Making Test Part B-A (TMT B-A), and fall risk index using the Physiological Profile Assessment (PPA). At the end of the trial, performance on LM, Block Design, and TMT B-A were significantly better for the Tai Chi group than the control group after adjusting for baseline test performance. The Tai Chi group also had significantly better composite PPA score and PPA parameter scores: knee extension strength, reaction time, postural sway, and lower limb proprioception. Combined center- and home-based Tai Chi training three times per week for 15 weeks significantly improved cognitive function and moderately reduced physiological fall risk in older adults with multiple-domain a-MCI. Tai Chi may be particularly beneficial to older adults with this condition. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

The Alzheimer's Disease Assessment Scale-Cognitive-Plus (ADAS-Cog-Plus): an expansion of the ADAS-Cog to improve responsiveness in MCI.

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Skinner, Jeannine; Carvalho, Janessa O; Potter, Guy G; Thames, April; Zelinski, Elizabeth; Crane, Paul K; Gibbons, Laura E

2012-12-01

The Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog) is widely used in AD, but may be less responsive to change when used in people with mild cognitive impairment (MCI). Participants from the Alzheimer's Disease Neuroimaging Initiative were administered a neuropsychological battery and 1.5 T MRI scans over 2-3 years. Informants were queried regarding functional impairments. Some participants had lumbar punctures to obtain cerebrospinal fluid (CSF). We added executive functioning (EF) and functional ability (FA) items to the ADAS-Cog to generate candidate augmented measures. We calibrated these candidates using baseline data (n = 811) and selected the best candidate that added EF items alone and that added EF and FA items. We selected candidates based on their responsiveness over three years in a training sample of participants with MCI (n = 160). We compared traditional ADAS-Cog scores with the two candidates based on their responsiveness in a validation sample of participants with MCI (n = 234), ability to predict conversion to dementia (n = 394), strength of association with baseline MRI (n = 394) and CSF biomarkers (n = 193). The selected EF candidate added category fluency (ADAS Plus EF), and the selected EF and FA candidate added category fluency, Digit Symbol, Trail Making, and five items from the Functional Assessment Questionnaire (ADAS Plus EF&FA). The ADAS Plus EF& FA performed as well as or better than traditional ADAS-Cog scores. Adding EF and FA items to the ADAS-Cog may improve responsiveness among people with MCI without impairing validity.

Peptides identify multiple hotspots within the ligand binding domain of the TNF receptor 2

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Lennick Michael

2003-01-01

Full Text Available Abstract Background Hotspots are defined as the minimal functional domains involved in protein:protein interactions and sufficient to induce a biological response. Results Here we describe the use of complex and high diversity phage display libraries to isolate peptides (called Hotspot Ligands or HSPLs which sub-divide the ligand binding domain of the tumor necrosis factor receptor 2 (TNFR2; p75 into multiple hotspots. We have shown that these libraries could generate HSPLs which not only subdivide hotspots on protein and non-protein targets but act as agonists or antagonists. Using this approach, we generated peptides which were specific for human TNFR2, could be competed by the natural ligands, TNFα and TNFβ and induced an unexpected biological response in a TNFR2-specific manner. Conclusions To our knowledge, this is the first report describing the dissection of the TNFR2 into biologically active hotspots with the concomitant identification of a novel and unexpected biological activity.

Predictive value of pyramidal lobe, percentage thyroid uptake and age for ablation outcome after 15 mCi fixed dose of radioiodine-131 in Graves’ disease

International Nuclear Information System (INIS)

Zaman, Maseeh uz; Fatima, Nosheen; Zaman, Unaiza; Sajjad, Zafar; Zaman, Areeba; Tahseen, Rabia

2015-01-01

The purpose was to find out the efficacy of fixed 15 mCi radioactive iodine-131 (RAI) dose and predictive values of various factors for inducing hypothyroidism in Graves’ disease (GD). Retrospective study conducted from January 2012 till August 2014. Patients with GD who had a technetium-99m thyroid scan, thyroid antibodies, received fixed 15 mCi RAI and did follow endocrine clinics for at least 6 months were selected. RAI was considered successful if within 6 months of RAI therapy patients developed hypothyroidism. Of the 370 patients with GD who had RAI during study period, 210 (57%) qualified study criteria. Mean age of patients was 48 ± 15 years with female: male ratio of 69:31, positive thyroid antibodies in 61%, means thyroid uptake of 15.09 ± 11.23%, and presence of pyramidal lobe in 40% of total population. Hypothyroidism was achieved in 161 (77%) patients while 49 (23%) patients failed to achieve it (remained either hyperthyroid or euthyroid on antithyroid medication). Patients who became hypothyroid were significantly younger with higher proportion of presence of thyroid antibodies and pyramidal lobe and lower percentage thyroid uptake than those who failed. Multiple logistic regression analysis revealed that age (odds ratio; OR = 2.074), pyramidal lobe (OR = 3.317), thyroid antibodies (OR = 8.198), and percentage thyroid uptake (OR = 3.043) were found to be significant prognostic risk factors for post-RAI hypothyroidism. Gender was found to have nonsignificant association with the development of hypothyroidism. Receiver operating characteristic analysis revealed age <42 years and thyroid uptake <15% as threshold values for the development of post-RAI hypothyroidism. We conclude that fixed (15 mCi) RAI dose is highly effective in rendering hypothyroidism in patients with GD. Age (≤42 years), thyroid uptake (≤15%) and presence of pyramidal lobe are strong predictors of hypothyroidism and must be considered for selecting optimal RAI dose

A Hybrid of Deep Network and Hidden Markov Model for MCI Identification with Resting-State fMRI.

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Suk, Heung-Il; Lee, Seong-Whan; Shen, Dinggang

2015-10-01

In this paper, we propose a novel method for modelling functional dynamics in resting-state fMRI (rs-fMRI) for Mild Cognitive Impairment (MCI) identification. Specifically, we devise a hybrid architecture by combining Deep Auto-Encoder (DAE) and Hidden Markov Model (HMM). The roles of DAE and HMM are, respectively, to discover hierarchical non-linear relations among features, by which we transform the original features into a lower dimension space, and to model dynamic characteristics inherent in rs-fMRI, i.e. , internal state changes. By building a generative model with HMMs for each class individually, we estimate the data likelihood of a test subject as MCI or normal healthy control, based on which we identify the clinical label. In our experiments, we achieved the maximal accuracy of 81.08% with the proposed method, outperforming state-of-the-art methods in the literature.

Multivariate trajectories across multiple domains of health-related quality of life in children with new-onset epilepsy.

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Sajobi, Tolulope T; Wang, Meng; Ferro, Mark A; Brobbey, Anita; Goodwin, Shane; Speechley, Kathy N; Wiebe, Samuel

2017-10-01

The diagnosis of epilepsy in children is known to impact the trajectory of their health-related quality of life (HRQOL) over time. However, there is limited knowledge about variations in longitudinal trajectories across multiple domains of HRQOL. This study aims to characterize the heterogeneity in HRQOL trajectories across multiple HRQOL domains and to evaluate predictors of differences among the identified trajectory groups in children with new-onset epilepsy. Data were obtained from the Health Related Quality of Life in Children with Epilepsy Study (HERQULES), a prospective multi-center study of 373 children newly diagnosed with new-onset epilepsy who were followed up over 2years. Child HRQOL and family factors were reported by parents, and clinical characteristics were reported by neurologists. Group-based multi-trajectory modeling was adopted to characterize longitudinal trajectories of HRQOL as measured by the individual domains of cognitive, emotional, physical, and social functioning in the 55-item Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55). Multinomial logistic regression was used to assess potential factors that explain differences among the identified latent trajectory groups. Three distinct HRQOL trajectory subgroups were identified in children with new-onset epilepsy based on HRQOL scores: "High" (44.7%), "Intermediate" (37.0%), and "Low" (18.3%). While most trajectory groups exhibited increasing scores over time on physical and social domains, both flat and declining trajectories were noted on emotional and cognitive domains. Less severe epilepsy, an absence of cognitive and behavioral problems, lower parental depression scores, better family functioning, and fewer family demands were associated with a "Higher" or "Intermediate" HRQOL trajectory. The course of HRQOL over time in children with new-onset epilepsy appears to follow one of three different trajectories. Addressing the clinical and psychosocial determinants identified

Adapting and applying a multiple domain model of condom use to Chinese college students.

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Xiao, Zhiwen; Palmgreen, Philip; Zimmerman, Rick; Noar, Seth

2010-03-01

This study adapts a multiple domain model (MDM) to explain condom use among a sample of sexually active Chinese college students. A cross-sectional survey was conducted and structural equation modeling was used to test the proposed model. Preparatory behaviors, theory of reasoned action (TRA)/theory of planned behavior variables, impulsivity, length of relationship, and alcohol use were significant direct predictors of condom use. The results suggest that MDM can provide a better understanding of heterosexual condom use among Chinese youth, and help in the design of HIV-preventive and safer sex interventions in China.

Six psychotropics for pre-symptomatic & early Alzheimer's (MCI, Parkinson's, and Huntington's disease modification

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Edward C Lauterbach

2016-01-01

Full Text Available The quest for neuroprotective drugs to slow the progression of neurodegenerative diseases (NDDs, including Alzheimer's disease (AD, Parkinson's disease (PD, and Huntington's disease (HD, has been largely unrewarding. Preclinical evidence suggests that repurposing quetiapine, lithium, valproate, fluoxetine, donepezil, and memantine for early and pre-symptomatic disease-modification in NDDs may be promising and can spare regulatory barriers. The literature of these psychotropics in early stage and pre-symptomatic AD, PD, and HD is reviewed and propitious findings follow. Mild cognitive impairment (MCI phase of AD: salutary human randomized controlled trial findings for low-dose lithium and, in selected patients, donepezil await replication. Pre-symptomatic AD: human epidemiological data indicate that lithium reduces AD risk. Animal model studies (AMS reveal encouraging results for quetiapine, lithium, donepezil, and memantine. Early PD: valproate AMS findings show promise. Pre-symptomatic PD: lithium and valproate AMS findings are encouraging. Early HD: uncontrolled clinical data indicate non-progression with lithium, fluoxetine, donepezil, and memantine. Pre-symptomatic HD: lithium and valproate are auspicious in AMS. Many other promising findings awaiting replication (valproate in MCI; lithium, valproate, fluoxetine in pre-symptomatic AD; lithium in early PD; lithium, valproate, fluoxetine in pre-symptomatic PD; donepezil in early HD; lithium, fluoxetine, memantine in pre-symptomatic HD are reviewed. Dose- and stage-dependent effects are considered. Suggestions for signal-enhancement in human trials are provided for each NDD stage.

Multiple functional self-association interfaces in plant TIR domains

NARCIS (Netherlands)

Zhang, Xiaoxiao; Bernoux, Maud; Bentham, Adam R; Newman, Toby E; Ve, Thomas; Casey, Lachlan W; Raaymakers, Tom M; Hu, Jian; Croll, Tristan I; Schreiber, Karl J; Staskawicz, Brian J; Anderson, Peter A; Sohn, Kee Hoon; Williams, Simon J; Dodds, Peter N; Kobe, Bostjan

2017-01-01

The self-association of Toll/interleukin-1 receptor/resistance protein (TIR) domains has been implicated in signaling in plant and animal immunity receptors. Structure-based studies identified different TIR-domain dimerization interfaces required for signaling of the plant nucleotide-binding

Neck and whole-body scanning with 5-mCi dose of (123)I as diagnostic tracer in patients with well-differentiated thyroid cancer.

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Gulzar, Z; Jana, S; Young, I; Bukberg, P; Yen, V; Naddaf, S; Abdel-Dayem, H M

2001-01-01

To determine whether a 5-mCi dose of 123I can be used as an effective radiotracer for assessing the presence of remnant thyroid tissue and for searching for metastatic lesions in patients with well-differentiated thyroid cancer as well as to attempt to ascertain whether a scan performed only at 4 hours is sufficient for accurate diagnosis and might replace the conventional protocol of scanning at both 4 hours and 24 hours. We prospectively studied 27 patients who had undergone near-total thyroidectomy and had a documented diagnosis of well-differentiated thyroid carcinoma. Patients underwent scanning after receiving a 5-mCi dose of 123I, at a time when they had discontinued thyroid replacement therapy and had a thyrotropin level in excess of 30 mIU/mL. Whole-body images at 4 hours and 24 hours were obtained and were compared with posttherapy scans obtained 5 to 7 days after administration of 131I. Scans were interpreted by two board-certified nuclear medicine physicians. Of the 27 patients, 2 (7.4%) showed discordance between the 123I scan performed at 24 hours and the posttherapy 131I scan. When 4-hour images after administration of 123I were compared with the posttherapy 131I scans, a discordance rate of 14.8% (4 of 27 patients) was noted. In addition, two of these four patients showed lesions on the 24-hour images that were not seen on the 4-hour images (one with new lung metastatic involvement and the other with a local recurrence in the lower neck area). The prognosis and treatment of these two patients were substantially changed by the result of the 24-hour images. On comparison of scans obtained after administration of a 5-mCi dose of 123I with those obtained after 131I therapy, we conclude that 5 mCi of 123I produces images that have excellent quality and resolution and also compare favorably with those obtained after 131I therapy. Furthermore, a decrease in the dose of 123I from 10 mCi to 5 mCi lowered the cost of the study without compromising the

Cytological profile of antibacterial FtsZ inhibitors and synthetic peptide MciZ

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Lidia Araujo-Bazan

2016-10-01

Full Text Available Cell division protein FtsZ is the organizer of the cytokinetic ring in almost all bacteria and a target for the discovery of new antibacterial agents that are needed to counter widespread antibiotic resistance. Bacterial cytological profiling, using quantitative microscopy, is a powerful approach for identifying the mechanism of action of antibacterial molecules affecting different cellular pathways. We have determined the cytological profile on Bacillus subtilis cells of a selection of small molecule inhibitors targeting FtsZ on different binding sites. FtsZ inhibitors lead to long undivided cells, impair the normal assembly of FtsZ into the midcell Z-rings, induce aberrant ring distributions, punctate FtsZ foci, membrane spots and also modify nucleoid length. Quantitative analysis of cell and nucleoid length combined, or the Z-ring distribution, allows categorizing FtsZ inhibitors and to distinguish them from antibiotics with other mechanisms of action, which should be useful for identifying new antibacterial FtsZ inhibitors. Biochemical assays of FtsZ polymerization and GTPase activity combined explain the cellular effects of the FtsZ polymer stabilizing agent PC190723 and its fragments. MciZ is a 40-aminoacid endogenous inhibitor of cell division normally expressed during sporulation in B. subtilis. Using FtsZ cytological profiling we have determined that exogenous synthetic MciZ is an effective inhibitor of B. subtilis cell division, Z-ring formation and localization. This finding supports our cell-based approach to screen for FtsZ inhibitors and opens new possibilities for peptide inhibitors of bacterial cell division.

Hierarchical anatomical brain networks for MCI prediction: revisiting volumetric measures.

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Luping Zhou

Full Text Available Owning to its clinical accessibility, T1-weighted MRI (Magnetic Resonance Imaging has been extensively studied in the past decades for prediction of Alzheimer's disease (AD and mild cognitive impairment (MCI. The volumes of gray matter (GM, white matter (WM and cerebrospinal fluid (CSF are the most commonly used measurements, resulting in many successful applications. It has been widely observed that disease-induced structural changes may not occur at isolated spots, but in several inter-related regions. Therefore, for better characterization of brain pathology, we propose in this paper a means to extract inter-regional correlation based features from local volumetric measurements. Specifically, our approach involves constructing an anatomical brain network for each subject, with each node representing a Region of Interest (ROI and each edge representing Pearson correlation of tissue volumetric measurements between ROI pairs. As second order volumetric measurements, network features are more descriptive but also more sensitive to noise. To overcome this limitation, a hierarchy of ROIs is used to suppress noise at different scales. Pairwise interactions are considered not only for ROIs with the same scale in the same layer of the hierarchy, but also for ROIs across different scales in different layers. To address the high dimensionality problem resulting from the large number of network features, a supervised dimensionality reduction method is further employed to embed a selected subset of features into a low dimensional feature space, while at the same time preserving discriminative information. We demonstrate with experimental results the efficacy of this embedding strategy in comparison with some other commonly used approaches. In addition, although the proposed method can be easily generalized to incorporate other metrics of regional similarities, the benefits of using Pearson correlation in our application are reinforced by the experimental

Multiple sclerosis masquerading as Alzheimer-type dementia: Clinical, radiological and pathological findings.

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Tobin, W O; Popescu, B F; Lowe, V; Pirko, I; Parisi, J E; Kantarci, K; Fields, J A; Bruns, M B; Boeve, B F; Lucchinetti, C F

2016-04-01

We report a comprehensive clinical, radiological, neuropsychometric and pathological evaluation of a woman with a clinical diagnosis of AD dementia (ADem), but whose autopsy demonstrated widespread demyelination, without Alzheimer disease (AD) pathology. Initial neuropsychometric evaluation suggested amnestic mild cognitive impairment (aMCI). Serial magnetic resonance images (MRI) images demonstrated the rate of increase in her ventricular volume was comparable to that of 46 subjects with aMCI who progressed to ADem, without accumulating white matter disease. Myelin immunohistochemistry at autopsy demonstrated extensive cortical subpial demyelination. Subpial lesions involved the upper cortical layers, and often extended through the entire width of the cortex. Multiple sclerosis (MS) can cause severe cortical dysfunction and mimic ADem. Cortical demyelination is not well detected by standard imaging modalities and may not be detected on autopsy without myelin immunohistochemistry. © The Author(s), 2015.

Rating knowledge sharing in cross-domain collaborative filtering.

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Li, Bin; Zhu, Xingquan; Li, Ruijiang; Zhang, Chengqi

2015-05-01

Cross-domain collaborative filtering (CF) aims to share common rating knowledge across multiple related CF domains to boost the CF performance. In this paper, we view CF domains as a 2-D site-time coordinate system, on which multiple related domains, such as similar recommender sites or successive time-slices, can share group-level rating patterns. We propose a unified framework for cross-domain CF over the site-time coordinate system by sharing group-level rating patterns and imposing user/item dependence across domains. A generative model, say ratings over site-time (ROST), which can generate and predict ratings for multiple related CF domains, is developed as the basic model for the framework. We further introduce cross-domain user/item dependence into ROST and extend it to two real-world cross-domain CF scenarios: 1) ROST (sites) for alleviating rating sparsity in the target domain, where multiple similar sites are viewed as related CF domains and some items in the target domain depend on their correspondences in the related ones; and 2) ROST (time) for modeling user-interest drift over time, where a series of time-slices are viewed as related CF domains and a user at current time-slice depends on herself in the previous time-slice. All these ROST models are instances of the proposed unified framework. The experimental results show that ROST (sites) can effectively alleviate the sparsity problem to improve rating prediction performance and ROST (time) can clearly track and visualize user-interest drift over time.

Characteristic patterns of cerebral blood perfusion and cognitive impairment in patients with Parkinsons disease

International Nuclear Information System (INIS)

Jeong, Y. J.; Park, M. J.; Cha, J. G.; Kim, S. H.; Kim, J. W.; Kang, D. Y.

2005-01-01

Parkinsons disease (PD) is a neurodegenerative disorder that represents cognitive impairment as well as motor symptoms. Even in the early stages of PD, cognitive alterations can be demonstrated by careful neuropsychological test. The purposes of this study are to investigate the pattern of cognitive impairment and the regional cerebral blood flow (rCBF) using Tc-99m HMPAO SPECT in patients with PD. One hundred and twenty two patients with PD and 35 control subjects participated in this study. Patients with PD who had dementia clinically or K-MMSE score below 25 points or with severe motor dysfunction to interfere with the tests were also excluded. They were all matched for age (61±10 vs 61±8), education periods (8.8±4.9 vs 8.8±4.5), and K-MMSE score (27±1.6 vs 27±1.5). All subjects were evaluated using the Seoul Neuropsychological Screening Battery (SNSB) and Tc-99m HMPAO SPECT with SPM software to measure rCBF. Patients with PD performed worse in digit span backward, Rey Complex Figure Test, visual memory, semantic fluency, stroop test, and alternating hand movement test(p<0.05) compared with control group. On SNSB test, 100 patients (82.0%) showed some abnormalities. Eighty-six patients (70.5%) showed frontal dysfunction, 47 (38.5%) memory impairment, 33 (27.0%) language dysfunction, 25 (20.5%) attention deficit and 22 (18.3%) visuospatial dysfunction in the order of frequency. Eight patients with PD showed single memory domain MCI and 28 single non-memory domain MCI (20 frontal dysfunction). Multiple domain MCI was found in 64 patients with PD. SPM analysis of the SPECT image revealed multiple perfusion deficit in the both frontal, temporal, both limbic lobes, Lt. parietal and Lt. Putamen. It is concluded that abnormalities of cognitive function be detected very commonly in patients with PD. MCI in PD patients is most frequently involved in the item of frontal lobe function. SPECT image might be helpful to explain cognitive impairment in some PD patients

Characteristic patterns of cerebral blood perfusion and cognitive impairment in patients with Parkinsons disease

Energy Technology Data Exchange (ETDEWEB)

Jeong, Y. J.; Park, M. J.; Cha, J. G.; Kim, S. H.; Kim, J. W.; Kang, D. Y. [Dong-A University College of medicine, Pusan (Korea, Republic of)

2005-07-01

Parkinsons disease (PD) is a neurodegenerative disorder that represents cognitive impairment as well as motor symptoms. Even in the early stages of PD, cognitive alterations can be demonstrated by careful neuropsychological test. The purposes of this study are to investigate the pattern of cognitive impairment and the regional cerebral blood flow (rCBF) using Tc-99m HMPAO SPECT in patients with PD. One hundred and twenty two patients with PD and 35 control subjects participated in this study. Patients with PD who had dementia clinically or K-MMSE score below 25 points or with severe motor dysfunction to interfere with the tests were also excluded. They were all matched for age (61{+-}10 vs 61{+-}8), education periods (8.8{+-}4.9 vs 8.8{+-}4.5), and K-MMSE score (27{+-}1.6 vs 27{+-}1.5). All subjects were evaluated using the Seoul Neuropsychological Screening Battery (SNSB) and Tc-99m HMPAO SPECT with SPM software to measure rCBF. Patients with PD performed worse in digit span backward, Rey Complex Figure Test, visual memory, semantic fluency, stroop test, and alternating hand movement test(p<0.05) compared with control group. On SNSB test, 100 patients (82.0%) showed some abnormalities. Eighty-six patients (70.5%) showed frontal dysfunction, 47 (38.5%) memory impairment, 33 (27.0%) language dysfunction, 25 (20.5%) attention deficit and 22 (18.3%) visuospatial dysfunction in the order of frequency. Eight patients with PD showed single memory domain MCI and 28 single non-memory domain MCI (20 frontal dysfunction). Multiple domain MCI was found in 64 patients with PD. SPM analysis of the SPECT image revealed multiple perfusion deficit in the both frontal, temporal, both limbic lobes, Lt. parietal and Lt. Putamen. It is concluded that abnormalities of cognitive function be detected very commonly in patients with PD. MCI in PD patients is most frequently involved in the item of frontal lobe function. SPECT image might be helpful to explain cognitive impairment in some

Development of the complex general linear model in the Fourier domain: application to fMRI multiple input-output evoked responses for single subjects.

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Rio, Daniel E; Rawlings, Robert R; Woltz, Lawrence A; Gilman, Jodi; Hommer, Daniel W

2013-01-01

A linear time-invariant model based on statistical time series analysis in the Fourier domain for single subjects is further developed and applied to functional MRI (fMRI) blood-oxygen level-dependent (BOLD) multivariate data. This methodology was originally developed to analyze multiple stimulus input evoked response BOLD data. However, to analyze clinical data generated using a repeated measures experimental design, the model has been extended to handle multivariate time series data and demonstrated on control and alcoholic subjects taken from data previously analyzed in the temporal domain. Analysis of BOLD data is typically carried out in the time domain where the data has a high temporal correlation. These analyses generally employ parametric models of the hemodynamic response function (HRF) where prewhitening of the data is attempted using autoregressive (AR) models for the noise. However, this data can be analyzed in the Fourier domain. Here, assumptions made on the noise structure are less restrictive, and hypothesis tests can be constructed based on voxel-specific nonparametric estimates of the hemodynamic transfer function (HRF in the Fourier domain). This is especially important for experimental designs involving multiple states (either stimulus or drug induced) that may alter the form of the response function.

Novel structural features in two ZHX homeodomains derived from a systematic study of single and multiple domains

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Owens Raymond J

2010-05-01

Full Text Available Abstract Background Zhx1 to 3 (zinc-fingers and homeoboxes form a set of paralogous genes encoding multi-domain proteins. ZHX proteins consist of two zinc fingers followed by five homeodomains. ZHXs have biological roles in cell cycle control by acting as co-repressors of the transcriptional regulator Nuclear Factor Y. As part of a structural genomics project we have expressed single and multi-domain fragments of the different human ZHX genes for use in structure determination. Results A total of 30 single and multiple domain ZHX1-3 constructs selected from bioinformatics protocols were screened for soluble expression in E. coli using high throughput methodologies. Two homeodomains were crystallized leading to structures for ZHX1 HD4 and ZHX2 HD2. ZHX1 HD4, although closest matched to homeodomains from 'homez' and 'engrailed', showed structural differences, notably an additional C-terminal helix (helix V which wrapped over helix I thereby making extensive contacts. Although ZHX2 HD2-3 was successfully expressed and purified, proteolysis occurred during crystallization yielding crystals of just HD2. The structure of ZHX2 HD2 showed an unusual open conformation with helix I undergoing 'domain-swapping' to form a homodimer. Conclusions Although multiple-domain constructs of ZHX1 selected by bioinformatics studies could be expressed solubly, only single homeodomains yielded crystals. The crystal structure of ZHX1 HD4 showed additional hydrophobic interactions relative to many known homeodomains via extensive contacts formed by the novel C-terminal helix V with, in particular, helix I. Additionally, the replacement of some charged covariant residues (which are commonly observed to form salt bridges in non-homeotherms such as the Drosophila 'engrailed' homeodomain, by apolar residues further increases hydrophobic contacts within ZHX1 HD4, and potentially stability, relative to engrailed homeodomain. ZHX1 HD4 helix V points away from the normally

The local domain wall position in ferromagnetic thin wires: simultaneous measurement of resistive and transverse voltages at multiple points

International Nuclear Information System (INIS)

Hanada, R.; Sugawara, H.; Aoki, Y.; Sato, H.; Shigeto, K.; Shinjo, T.; Ono, T.; Miyajima, H.

2002-01-01

We have simultaneously measured the field dependences of voltages at multiple pairs of resistance and transverse voltage probes in ferromagnetic wires (with either magnetic or non-magnetic voltage probes). Both the resistive (through the giant magnetoresistance and anisotropic magnetoresistance) and transverse voltages (through the planar Hall effect) exhibit abrupt jumps, reflecting discrete motion of domain walls or rotations of magnetization. Voltage probes, even if non-magnetic, are found to affect the jump fields depending on the sample conditions. We demonstrate that the specific information on the domain (wall) motion along a thin ferromagnetic wire could be obtained from the jump fields. (author)

Impairment in proverb interpretation as an executive function deficit in patients with amnestic mild cognitive impairment and early Alzheimer's disease.

Science.gov (United States)

Leyhe, Thomas; Saur, Ralf; Eschweiler, Gerhard W; Milian, Monika

2011-01-01

Proverb interpretation is assumed to reflect executive functions. We hypothesized that proverb interpretation is impaired in patients with amnestic mild cognitive impairment (aMCI) diagnosed as single-domain impairment by common neuropsychological testing. We compared performance in a proverb interpretation test in single-domain aMCI patients and patients with early Alzheimer's disease (EAD). The groups with aMCI and EAD performed significantly worse than healthy controls. Both patient groups gave concrete answers with a similar frequency. However, patients with EAD tended to give senseless answers more frequently. Our data suggest that in patients diagnosed as single-domain aMCI, deterioration of executive functions is detectable with subtle and appropriate neuropsychological testing. Implementation of these procedures may improve the early prediction of AD.

Assessing Working Memory in Mild Cognitive Impairment with Serial Order Recall.

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Emrani, Sheina; Libon, David J; Lamar, Melissa; Price, Catherine C; Jefferson, Angela L; Gifford, Katherine A; Hohman, Timothy J; Nation, Daniel A; Delano-Wood, Lisa; Jak, Amy; Bangen, Katherine J; Bondi, Mark W; Brickman, Adam M; Manly, Jennifer; Swenson, Rodney; Au, Rhoda

2018-01-01

Working memory (WM) is often assessed with serial order tests such as repeating digits backward. In prior dementia research using the Backward Digit Span Test (BDT), only aggregate test performance was examined. The current research tallied primacy/recency effects, out-of-sequence transposition errors, perseverations, and omissions to assess WM deficits in patients with mild cognitive impairment (MCI). Memory clinic patients (n = 66) were classified into three groups: single domain amnestic MCI (aMCI), combined mixed domain/dysexecutive MCI (mixed/dys MCI), and non-MCI where patients did not meet criteria for MCI. Serial order/WM ability was assessed by asking participants to repeat 7 trials of five digits backwards. Serial order position accuracy, transposition errors, perseverations, and omission errors were tallied. A 3 (group)×5 (serial position) repeated measures ANOVA yielded a significant group×trial interaction. Follow-up analyses found attenuation of the recency effect for mixed/dys MCI patients. Mixed/dys MCI patients scored lower than non-MCI patients for serial position 3 (p Mixed/dys MCI patients also produced more transposition errors than both groups (p order parameters obtained from the BDT may provide a useful operational definition as well as additional diagnostic information regarding working memory deficits in MCI.

Lexical factors and cerebral regions influencing verbal fluency performance in MCI.

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Clark, D G; Wadley, V G; Kapur, P; DeRamus, T P; Singletary, B; Nicholas, A P; Blanton, P D; Lokken, K; Deshpande, H; Marson, D; Deutsch, G

2014-02-01

To evaluate assumptions regarding semantic (noun), verb, and letter fluency in mild cognitive impairment (MCI) and Alzheimer disease (AD) using novel techniques for measuring word similarity in fluency lists and a region of interest (ROI) analysis of gray matter correlates. Fifty-eight individuals with normal cognition (NC, n=25), MCI (n=23), or AD (n=10) underwent neuropsychological tests, including 10 verbal fluency tasks (three letter tasks [F, A, S], six noun categories [animals, water creatures, fruits and vegetables, tools, vehicles, boats], and verbs). All pairs of words generated by each participant on each task were compared in terms of semantic (meaning), orthographic (spelling), and phonemic (pronunciation) similarity. We used mixed-effects logistic regression to determine which lexical factors were predictive of word adjacency within the lists. Associations between each fluency raw score and gray matter volumes in sixteen ROIs were identified by means of multiple linear regression. We evaluated causal models for both types of analyses to specify the contributions of diagnosis and various mediator variables to the outcomes of word adjacency and fluency raw score. Semantic similarity between words emerged as the strongest predictor of word adjacency for all fluency tasks, including the letter fluency tasks. Semantic similarity mediated the effect of cognitive impairment on word adjacency only for three fluency tasks employing a biological cue. Orthographic similarity was predictive of word adjacency for the A and S tasks, while phonemic similarity was predictive only for the S task and one semantic task (vehicles). The ROI analysis revealed different patterns of correlations among the various fluency tasks, with the most common associations in the right lower temporal and bilateral dorsal frontal regions. Following correction with gray matter volumes from the opposite hemisphere, significant associations persisted for animals, vehicles, and a composite

Impairment in Proverb Interpretation as an Executive Function Deficit in Patients with Amnestic Mild Cognitive Impairment and Early Alzheimer’s Disease

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Thomas Leyhe

2011-01-01

Full Text Available Background/Aims: Proverb interpretation is assumed to reflect executive functions. We hypothesized that proverb interpretation is impaired in patients with amnestic mild cognitive impairment (aMCI diagnosed as single-domain impairment by common neuropsychological testing. Methods: We compared performance in a proverb interpretation test in single-domain aMCI patients and patients with early Alzheimer’s disease (EAD. Results: The groups with aMCI and EAD performed significantly worse than healthy controls. Both patient groups gave concrete answers with a similar frequency. However, patients with EAD tended to give senseless answers more frequently. Conclusions: Our data suggest that in patients diagnosed as single-domain aMCI, deterioration of executive functions is detectable with subtle and appropriate neuropsychological testing. Implementation of these procedures may improve the early prediction of AD.

Multiple nonlinear Bragg diffraction of femtosecond laser pulses in a {\\chi^{(2)}} photonic lattice with hexagonal domains

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Vyunishev, A. M.; Arkhipkin, V. G.; Baturin, I. S.; Akhmatkhanov, A. R.; Shur, V. Ya; Chirkin, A. S.

2018-04-01

The frequency doubling of femtosecond laser pulses in a two-dimensional (2D) rectangular nonlinear photonic lattice with hexagonal domains is studied experimentally and theoretically. The broad fundamental spectrum enables frequency conversion under nonlinear Bragg diffraction for a series of transverse orders at a fixed longitudinal quasi-phase-matching order. The consistent nonstationary theory of the frequency doubling of femtosecond laser pulses is developed using the representation based on the reciprocal lattice of the structure. The calculated spatial distribution of the second-harmonic spectral intensity agrees well with the experimental data. The condition for multiple nonlinear Bragg diffraction in a 2D nonlinear photonic lattice is offered. The hexagonal shape of the domains contributes to multibeam second harmonic excitation. The maximum conversion efficiency for a series of transverse orders in the range 0.01%-0.03% is obtained.

MOTORES DE COMBUSTIÓN INTERNA (MCI) OPERANDO CON MEZCLAS DE ETANOL GASOLINA: REVISIÓN

OpenAIRE

Alexander García Mariaca; Edwin Darío Cendales Ladino; Andrés Felipe Eslava Sarmiento

2016-01-01

En este artículo se presenta una revisión bibliográfica acerca del uso de etanol como combustible en motores de combustión interna de encendido provocado (MCI-EP). Este empieza por una breve descripción de las diversas formas de producción y principales productores en el mundo de etanol, para posteriormente profundizar en el desempeño, combustión y las emisiones en MCIEP al operar con diferentes mezclas de etanol y gasolina convencional. Los resultados obtenidos por los diferentes autores de ...

Including persistency of impairment in mild cognitive impairment classification enhances prediction of 5-year decline.

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Vandermorris, Susan; Hultsch, David F; Hunter, Michael A; MacDonald, Stuart W S; Strauss, Esther

2011-02-01

Although older adults with Mild Cognitive Impairment (MCI) show elevated rates of conversion to dementia as a group, heterogeneity of outcomes is common at the individual level. Using data from a prospective 5-year longitudinal investigation of cognitive change in healthy older adults (N = 262, aged 64-92 years), this study addressed limitations in contemporary MCI identification procedures which rely on single occasion assessment ("Single-Assessment [SA] MCI") by evaluating an alternate operational definition of MCI requiring evidence of persistent cognitive impairment over multiple-testing sessions ("Multiple-Assessment [MA] MCI"). As hypothesized, prevalence of SA-MCI exceeded that of MA-MCI. Further, the MA-MCI groups showed lower baseline cognitive and functional performance and steeper cognitive decline compared with Control and SA-MCI group. Results are discussed with reference to retest effects and clinical implications.

Preclinical Polymodal Hallucinations for 13 Years before Dementia with Lewy Bodies

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Abbate, Carlo; Trimarchi, Pietro Davide; Inglese, Silvia; Viti, Niccolò; Cantatore, Alessandra; De Agostini, Lisa; Pirri, Federico; Marino, Lorenza; Bagarolo, Renzo

2014-01-01

Objective. We describe a case of dementia with Lewy bodies (DLB) that presented long-lasting preclinical complex polymodal hallucinations. Background. Few studies have deeply investigated the characteristics of hallucinations in DLB, especially in the preclinical phase. Moreover, the clinical phenotype of mild cognitive impairment-(MCI-) DLB is poorly understood. Methods. The patient was followed for 4 years and a selective phenomenological and cognitive study was performed at the predementia stage. Results. The phenomenological study showed the presence of hypnagogic and hypnopompic hallucinations that allowed us to make a differential diagnosis between DLB and Charles Bonnet syndrome (CBS). The neuropsychological evaluation showed a multiple domain without amnesia MCI subtype with prefrontal dysexecutive, visuoperceptual, and visuospatial impairments and simultanagnosia, which has not previously been reported in MCI-DLB. Conclusions. This study extends the prognostic value of hallucinations for DLB to the preclinical phases. It supports and refines the MCI-DLB concept and identifies simultanagnosia as a possible early cognitive marker. Finally, it confirms an association between hallucinations and visuoperceptual impairments at an intermediate stage of the disease course and strongly supports the hypothesis that hallucinations in the earliest stages of DLB may reflect a narcolepsy-like REM-sleep disorder. PMID:24868122

Effective Domain Partitioning for Multi-Clock Domain IP Core Wrapper Design under Power Constraints

Science.gov (United States)

Yu, Thomas Edison; Yoneda, Tomokazu; Zhao, Danella; Fujiwara, Hideo

The rapid advancement of VLSI technology has made it possible for chip designers and manufacturers to embed the components of a whole system onto a single chip, called System-on-Chip or SoC. SoCs make use of pre-designed modules, called IP-cores, which provide faster design time and quicker time-to-market. Furthermore, SoCs that operate at multiple clock domains and very low power requirements are being utilized in the latest communications, networking and signal processing devices. As a result, the testing of SoCs and multi-clock domain embedded cores under power constraints has been rapidly gaining importance. In this research, a novel method for designing power-aware test wrappers for embedded cores with multiple clock domains is presented. By effectively partitioning the various clock domains, we are able to increase the solution space of possible test schedules for the core. Since previous methods were limited to concurrently testing all the clock domains, we effectively remove this limitation by making use of bandwidth conversion, multiple shift frequencies and properly gating the clock signals to control the shift activity of various core logic elements. The combination of the above techniques gains us greater flexibility when determining an optimal test schedule under very tight power constraints. Furthermore, since it is computationally intensive to search the entire expanded solution space for the possible test schedules, we propose a heuristic 3-D bin packing algorithm to determine the optimal wrapper architecture and test schedule while minimizing the test time under power and bandwidth constraints.

Volume of interest-based [18F]fluorodeoxyglucose PET discriminates MCI converting to Alzheimer's disease from healthy controls. A European Alzheimer's Disease Consortium (EADC study

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M. Pagani

2015-01-01

Full Text Available An emerging issue in neuroimaging is to assess the diagnostic reliability of PET and its application in clinical practice. We aimed at assessing the accuracy of brain FDG-PET in discriminating patients with MCI due to Alzheimer's disease and healthy controls. Sixty-two patients with amnestic MCI and 109 healthy subjects recruited in five centers of the European AD Consortium were enrolled. Group analysis was performed by SPM8 to confirm metabolic differences. Discriminant analyses were then carried out using the mean FDG uptake values normalized to the cerebellum computed in 45 anatomical volumes of interest (VOIs in each hemisphere (90 VOIs as defined in the Automated Anatomical Labeling (AAL Atlas and on 12 meta-VOIs, bilaterally, obtained merging VOIs with similar anatomo-functional characteristics. Further, asymmetry indexes were calculated for both datasets. Accuracy of discrimination by a Support Vector Machine (SVM and the AAL VOIs was tested against a validated method (PALZ. At the voxel level SMP8 showed a relative hypometabolism in the bilateral precuneus, and posterior cingulate, temporo-parietal and frontal cortices. Discriminant analysis classified subjects with an accuracy ranging between .91 and .83 as a function of data organization. The best values were obtained from a subset of 6 meta-VOIs plus 6 asymmetry values reaching an area under the ROC curve of .947, significantly larger than the one obtained by the PALZ score. High accuracy in discriminating MCI converters from healthy controls was reached by a non-linear classifier based on SVM applied on predefined anatomo-functional regions and inter-hemispheric asymmetries. Data pre-processing was automated and simplified by an in-house created Matlab-based script encouraging its routine clinical use. Further validation toward nonconverter MCI patients with adequately long follow-up is needed.

Ocean acidification in the coastal zone from an organism's perspective: multiple system parameters, frequency domains, and habitats.

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Waldbusser, George G; Salisbury, Joseph E

2014-01-01

Multiple natural and anthropogenic processes alter the carbonate chemistry of the coastal zone in ways that either exacerbate or mitigate ocean acidification effects. Freshwater inputs and multiple acid-base reactions change carbonate chemistry conditions, sometimes synergistically. The shallow nature of these systems results in strong benthic-pelagic coupling, and marine invertebrates at different life history stages rely on both benthic and pelagic habitats. Carbonate chemistry in coastal systems can be highly variable, responding to processes with temporal modes ranging from seconds to centuries. Identifying scales of variability relevant to levels of biological organization requires a fuller characterization of both the frequency and magnitude domains of processes contributing to or reducing acidification in pelagic and benthic habitats. We review the processes that contribute to coastal acidification with attention to timescales of variability and habitats relevant to marine bivalves.

ASIC3 Channels Integrate Agmatine and Multiple Inflammatory Signals through the Nonproton Ligand Sensing Domain

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Cao Hui

2010-12-01

Full Text Available Abstract Background Acid-sensing ion channels (ASICs have long been known to sense extracellular protons and contribute to sensory perception. Peripheral ASIC3 channels represent natural sensors of acidic and inflammatory pain. We recently reported the use of a synthetic compound, 2-guanidine-4-methylquinazoline (GMQ, to identify a novel nonproton sensing domain in the ASIC3 channel, and proposed that, based on its structural similarity with GMQ, the arginine metabolite agmatine (AGM may be an endogenous nonproton ligand for ASIC3 channels. Results Here, we present further evidence for the physiological correlation between AGM and ASIC3. Among arginine metabolites, only AGM and its analog arcaine (ARC activated ASIC3 channels at neutral pH in a sustained manner similar to GMQ. In addition to the homomeric ASIC3 channels, AGM also activated heteromeric ASIC3 plus ASIC1b channels, extending its potential physiological relevance. Importantly, the process of activation by AGM was highly sensitive to mild acidosis, hyperosmolarity, arachidonic acid (AA, lactic acid and reduced extracellular Ca2+. AGM-induced ASIC3 channel activation was not through the chelation of extracellular Ca2+ as occurs with increased lactate, but rather through a direct interaction with the newly identified nonproton ligand sensing domain. Finally, AGM cooperated with the multiple inflammatory signals to cause pain-related behaviors in an ASIC3-dependent manner. Conclusions Nonproton ligand sensing domain might represent a novel mechanism for activation or sensitization of ASIC3 channels underlying inflammatory pain-sensing under in vivo conditions.

SymptoMScreen: A Tool for Rapid Assessment of Symptom Severity in MS Across Multiple Domains.

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Green, R; Kalina, J; Ford, R; Pandey, K; Kister, I

2017-01-01

The objective of this study was to describe SymptoMScreen, an in-house developed tool for rapid assessment of MS symptom severity in routine clinical practice, and to validate SymptoMScreen against Performance Scales (PS). MS patients typically experience symptoms in many neurologic domains. A tool that would enable MS patients to efficiently relay their symptom severity across multiple domains to the healthcare providers could lead to improved symptom management. We developed "SymptoMScreen," a battery of 7-point Likert scales for 12 distinct domains commonly affected by MS: mobility, dexterity, body pain, sensation, bladder function, fatigue, vision, dizziness, cognition, depression, and anxiety. We administered SymptoMScreen and PS scales to consecutive MS patients at a specialty MS Care Center. We assessed the criterion and construct validity of SymptoMScreen by calculating Spearmen rank correlations between the SymptoMScreen composite score and PS composite score, and between SymptoMScreen subscale and the respective PS subscale scores, where applicable. A total of 410 patients with MS (age 46.6 ± 12.9 years; 74% female; mean disease duration 12.2 ± 8.7 years) completed the SymptoMScreen and PSs during their clinic visit. Composite SymptoMScreen score correlated strongly with combined PS score (r = 0.88, p MS. It has excellent criterion and construct validity. SymptoMScreen is patient and clinician friendly, takes approximately one minute to complete, and can help better document, understand, and manage patients' symptoms in routine clinical practice. SymptoMScreen is freely available to clinicians and researchers.

Difference of cerebral activation between healthy volunteers and MCI-patients during navigation in a virtual reality environment. A parametric study using O15 H2O-PET

International Nuclear Information System (INIS)

Drzezga, A.; Wermke, M.D.; Schwaiger, M.; Grimmer, T.; Foerstl, H.; Kurz, A.

2002-01-01

Aim: To assess the regional cerebral activation during navigation in a virtual reality (VR) environment in healthy volunteers and patients with mild cognitive impairment (MCI) to identify possible differences in cerebral processing of a complex cognitive task. Materials and Methods: A computer-based VR-system has been developed that allows movements in a virtual labyrinth using a special space-mouse and 3-dimensional perception by shutter-glasses. In 11 healthy, right-handed volunteers (3 female, age 66+/-9 years) and 9 patients with MCI (3 female, 69+/-10 years, diagnosis according to criteria of the Mayo-Clinic) twelve H215O PET-scans were performed (each 370 MBq i.v.-bolus). During the scan subjects had to navigate actively from startpoint to a predefined destination point. Three difficulty levels were presented, 4 times each, in randomized order. Test performance (speed, mistakes) was co-registered. PET data were analyzed using statistical parametric mapping (SPM99, Wellcome Inst., London, UK) including correlation analysis with the acquired test performance results. A significance threshold of p<0,001 uncorrected was applied. Results: In both groups a similar network of extended cerebral activation was identified during active navigation, including maxima in the cerebellum, premotor cortex (Brodmann area [BA] 6), parietal cortex (BA 7, 40) and posterior cingulate cortex (BA 31). However, in MCI-patients a significantly stronger activation of anterior cingulate cortex (BA 24), prefrontal cortex (BA 8) and parietal cortex (BA 40) was observed, as compared to healthy volunteers. Conclusion: The applied combination of PET and VR-technology allows to examine the processing of complex cognitive tasks in the brain. During active navigation significant differences have been observed between the activated cerebral networks in MCI-patients and healthy volunteers. In MCI-patients stronger activation has been identified in cerebral regions associated with attention and

Microcystin Biosynthesis and mcyA Expression in Geographically Distinct Microcystis Strains under Different Nitrogen, Phosphorus, and Boron Regimes

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Ankita Srivastava

2016-01-01

Full Text Available Roles of nutrients and other environmental variables in development of cyanobacterial bloom and its toxicity are complex and not well understood. We have monitored the photoautotrophic growth, total microcystin concentration, and microcystins synthetase gene (mcyA expression in lab-grown strains of Microcystis NIES 843 (reference strain, KW (Wangsong Reservoir, South Korea, and Durgakund (Varanasi, India under different nutrient regimes (nitrogen, phosphorus, and boron. Higher level of nitrogen and boron resulted in increased growth (avg. 5 and 6.5 Chl a mg/L, resp., total microcystin concentrations (avg. 1.185 and 7.153 mg/L, resp., and mcyA transcript but its expression was not directly correlated with total microcystin concentrations in the target strains. Interestingly, Durgakund strain had much lower microcystin content and lacked microcystin-YR variant over NIES 843 and KW. It is inferred that microcystin concentration and its variants are strain specific. We have also examined the heterotrophic bacteria associated with cyanobacterial bloom in Durgakund Pond and Wangsong Reservoir which were found to be enriched in Alpha-, Beta-, and Gammaproteobacteria and that could influence the bloom dynamics.

Long-term Associations Between Physical Frailty and Performance in Specific Cognitive Domains.

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Bunce, David; Batterham, Philip J; Mackinnon, Andrew J

2018-02-01

No longitudinal epidemiological research has reported associations between physical frailty and performance in specific cognitive domains. Our aim was to investigate whether such associations existed in the absence of accompanying neurodegenerative disorders such as mild cognitive impairment (MCI) and dementia. We addressed this issue in a population-based sample of 896 adults aged 70 years and older over 4 waves of data covering a 12-year period. Physical frailty was assessed and a cognitive battery included measures of processing speed, verbal fluency, face and word recognition, episodic memory and simple and choice reaction time (RT). Latent growth models showed frailty was associated with poorer baseline performance in processing speed, verbal fluency, simple and choice RT, and choice intraindividual RT variability. However, no significant effects of frailty on slopes of cognition were observed, suggesting that frailty was not associated with cognitive decline. Importantly, when the models took possible dementia into account, significant effects were retained suggesting that differences were not associated with dementia-related neurodegenerative disorders. The findings suggest that frailty-related cognitive deficits may exist independently of mechanisms underpinning neurodegenerative disorders such as MCI and dementia. If confirmed, this finding suggests a new avenue for preventative and therapeutic interventions in clinical and public health contexts for older adults. © The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Stable multiple-layer stationary solutions of a semilinear parabolic equation in two-dimensional domains

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Arnaldo Simal do Nascimento

1997-12-01

Full Text Available We use $Gamma$--convergence to prove existence of stable multiple--layer stationary solutions (stable patterns to the reaction--diffusion equation. $$ eqalign{ {partial v_varepsilon over partial t} =& varepsilon^2, hbox{div}, (k_1(xabla v_varepsilon + k_2(x(v_varepsilon -alpha(Beta-v_varepsilon (v_varepsilon -gamma_varepsilon(x,,hbox{ in }Omegaimes{Bbb R}^+ cr &v_varepsilon(x,0 = v_0 quad {partial v_varepsilon over partial widehat{n}} = 0,, quadhbox{ for } xin partialOmega,, t >0,.} $$ Given nested simple closed curves in ${Bbb R}^2$, we give sufficient conditions on their curvature so that the reaction--diffusion problem possesses a family of stable patterns. In particular, we extend to two-dimensional domains and to a spatially inhomogeneous source term, a previous result by Yanagida and Miyata.

Performance of a sample of patients with Mild Cognitive Impairment (MCI), Alzheimer's Disease (AD) and healthy elderly on a lexical decision test (LDT) as a measure of pre-morbid intelligence

OpenAIRE

Serrao, Valéria Trunkl; Brucki, Sônia Maria Dozzi; Campanholo, Kenia Repiso; Mansur, Letícia Lessa; Nitrini, Ricardo; Miotto, Eliane Correa

2015-01-01

Objective: The objective of this study was to describe the performance of healthy elderly patients with aging-related pathologies (MCI) and patients with AD on a lexical decision test. Methods: The study included 38 healthy elderly subjects, 61 MCI and 26 AD patients from the Neurology Department of the Hospital das Clinicas, Behavioral and Cognitive Neurology Group. The neuropsychological instruments included the episodic memory test (RAVLT), subtests from the WAIS-III (Matrix Reasoning and...

Identificação do gene mcyA em florações naturais de Radiocystis fernandoi, em um tributário do reservatório de Rosana, Brasil - doi: 10.4025/actascibiolsci.v33i3.6802 Identification of the mcyA gene in natural blooms of Radiocystis fernandoi from a tributary of the Rosana reservoir, Brazil - doi: 10.4025/actascibiolsci.v33i3.6802

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Sônia Maria Alves Pinto Prioli

2011-07-01

Full Text Available As cianobactérias são conhecidamente produtoras de toxinas. Dentro de uma mesma espécie, podemos encontrar variedades tóxicas e não-tóxicas, impossíveis de diferenciação apenas pela morfologia. A principal toxina produzida pelas cianobactérias é a microcistina. Esta proteína é biossintetizada por um grupo de genes conhecidos como mcy. A detecção destes genes a partir de PCR permite a distinção das variedades tóxicas e não-tóxicas. Desse modo, o objetivo desse trabalho foi investigar a ocorrência de florações produtoras de toxinas em um rio tributário do reservatório de Rosana, via amplificação do gene mcyA por PCR. Foram coletadas duas amostras de água da subsuperfície. As duas amostras coletadas no rio do Corvo foram dominadas pela espécie Radiocystis fernandoi e apresentaram resultados positivos para a presença do gene mcyA, confirmando o potencial tóxico dessa espécie. Os resultados representam alerta sobre a qualidade da água do rio do Corvo. A técnica PCR foi eficiente para a rápida detecção de cianobactérias produtoras de toxinas, inclusive podendo ser utilizada antes mesmo do agravamento das condições ambientais pela produção de toxinas, além de apresentar baixo custo.Cyanobacterias are known as toxin producers. Within the same species, toxic and non-toxic varieties can be found and it is impossible to differentiate them only by morphology. The most important toxin produced by cyanobacteria is microcystin. This protein is synthesized by a cluster of genes known as mcy. The detection of these genes by PCR allows the differentiation of the producing toxin strain from the non-producing toxin strain. Thus, the goal of this work was to investigate the occurrence of toxigenic blooms of cyanobacteria in the Corvo River through PCR amplification of mcyA gene. For this, two samples of blooms of cyanobacteria were collected in Corvo River. Both samples were dominated by Radiocystis fernandoi and presented

"You've got a friend in me": can social networks mediate the relationship between mood and MCI?

OpenAIRE

Yates, Jennifer A.; Clare, Linda; Woods, Robert T.

2017-01-01

Background Social networks can change with age, for reasons that are adaptive or unwanted. Social engagement is beneficial to both mental health and cognition, and represents a potentially modifiable factor. Consequently this study explored this association and assessed whether the relationship between mild cognitive impairment (MCI) and mood problems was mediated by social networks. Methods This study includes an analysis of data from the Cognitive Function and Ageing Study Wales (CFAS Wales...

High levels of antibodies to multiple domains and strains of VAR2CSA correlate with the absence of placental malaria in Cameroonian women living in an area of high Plasmodium falciparum transmission

DEFF Research Database (Denmark)

Tutterrow, Yeung L; Avril, Marion; Singh, Kavita

2012-01-01

erythrocytes and mediates binding to chondroitin sulfate A, initiating inflammation and disrupting homeostasis at the maternal-fetal interface. Although antibodies can prevent sequestration, it is unclear whether parasite clearance is due to antibodies to a single Duffy binding-like (DBL) domain...... or to an extensive repertoire of antibodies to multiple DBL domains and allelic variants. Accordingly, plasma samples collected longitudinally from pregnant women were screened for naturally acquired antibodies against an extensive panel of VAR2CSA proteins, including 2 to 3 allelic variants for each of 5 different...... DBL domains. Analyses were performed on plasma samples collected from 3 to 9 months of pregnancy from women living in areas in Cameroon with high and low malaria transmission. The results demonstrate that high antibody levels to multiple VAR2CSA domains, rather than a single domain, were associated...

Increased Amplitude of the P3a ERP Component as a Neurocognitive Marker for Differentiating Amnestic Subtypes of Mild Cognitive Impairment

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Kenia S. Correa-Jaraba

2018-02-01

Full Text Available The event-related potential (ERP technique has been shown to be useful for evaluating changes in brain electrical activity associated with different cognitive processes, particularly in Alzheimer’s disease (AD. Longitudinal studies have shown that a high proportion of people with amnestic mild cognitive impairment (aMCI go on to develop AD. aMCI is divided into two subtypes according to the presence of memory impairment only (single-domain aMCI: sdaMCI or impairment of memory and other cognitive domains (multi-domain aMCI: mdaMCI. The main aim of this study was to examine the effects of sdaMCI and mdaMCI on the P3a ERP component associated with the involuntary orientation of attention toward unattended infrequent novel auditory stimuli. Participants performed an auditory-visual distraction-attention task, in which they were asked to ignore the auditory stimuli (standard, deviant, and novel and to attend to the visual stimuli (responding to some of them: Go stimuli. P3a was identified in the Novel minus Standard difference waveforms, and reaction times (RTs and hits (in response to Go stimuli were also analyzed. Participants were classified into three groups: Control, 20 adults (mean age (M: 65.8 years; sdaMCI, 19 adults (M: 67 years; and mdaMCI, 11 adults (M: 71 years. In all groups, the RTs were significantly longer when Go stimuli were preceded by novel (relative to standard auditory stimuli, suggesting a distraction effect triggered by novel stimuli; mdaMCI participants made significantly fewer hits than control and sdaMCI participants. P3a comprised two consecutive phases in all groups: early-P3a (e-P3a, which may reflect the orienting response toward the irrelevant stimuli, and late-P3a (l-P3a, which may be a correlate of subsequent evaluation of these stimuli. The e-P3a amplitude was significantly larger in mdaMCI than in sdaMCI participants, and the l-P3a amplitude was significantly larger in mdaMCI than in sdaMCI and Control

Multiple γ-secretase product peptides are coordinately increased in concentration in the cerebrospinal fluid of a subpopulation of sporadic Alzheimer’s disease subjects

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Hata Saori

2012-04-01

Full Text Available Abstract Background Alcadeinα (Alcα is a neuronal membrane protein that colocalizes with the Alzheimer's amyloid-β precursor protein (APP. Successive cleavage of APP by β- and γ-secretases generates the aggregatable amyloid-β peptide (Aβ, while cleavage of APP or Alcα by α- and γ-secretases generates non-aggregatable p3 or p3-Alcα peptides. Aβ and p3-Alcα can be recovered from human cerebrospinal fluid (CSF. We have previously reported alternative processing of APP and Alcα in the CSF of some patients with sporadic mild cognitive impairment (MCI and AD (SAD. Results Using the sandwich enzyme-linked immunosorbent assay (ELISA system that detects total p3-Alcα, we determined levels of total p3-Alcα in CSF from subjects in one of four diagnostic categories (elderly controls, MCI, SAD, or other neurological disease derived from three independent cohorts. Levels of Aβ40 correlated with levels of total p3-Alcα in all cohorts. Conclusions We confirm that Aβ40 is the most abundant Aβ species, and we propose a model in which CSF p3-Alcα can serve as a either (1 a nonaggregatable surrogate marker for γ-secretase activity; (2 as a marker for clearance of transmembrane domain peptides derived from integral protein catabolism; or (3 both. We propose the specification of an MCI/SAD endophenotype characterized by co-elevation of levels of both CSF p3-Alcα and Aβ40, and we propose that subjects in this category might be especially responsive to therapeutics aimed at modulation of γ-secretase function and/or transmembrane domain peptide clearance. These peptides may also be used to monitor the efficacy of therapeutics that target these steps in Aβ metabolism

Spatial and Temporal Distribution of Multiple Cropping Indices in the North China Plain Using a Long Remote Sensing Data Time Series

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Yan Zhao

2016-04-01

Full Text Available Multiple cropping provides China with a very important system of intensive cultivation, and can effectively enhance the efficiency of farmland use while improving regional food production and security. A multiple cropping index (MCI, which represents the intensity of multiple cropping and reflects the effects of climate change on agricultural production and cropping systems, often serves as a useful parameter. Therefore, monitoring the dynamic changes in the MCI of farmland over a large area using remote sensing data is essential. For this purpose, nearly 30 years of MCIs related to dry land in the North China Plain (NCP were efficiently extracted from remotely sensed leaf area index (LAI data from the Global LAnd Surface Satellite (GLASS. Next, the characteristics of the spatial-temporal change in MCI were analyzed. First, 2162 typical arable sample sites were selected based on a gridded spatial sampling strategy, and then the LAI information was extracted from the samples. Second, the Savizky-Golay filter was used to smooth the LAI time-series data of the samples, and then the MCIs of the samples were obtained using a second-order difference algorithm. Finally, the geo-statistical Kriging method was employed to map the spatial distribution of the MCIs and to obtain a time-series dataset of the MCIs of dry land over the NCP. The results showed that all of the MCIs in the NCP showed an increasing trend over the entire study period and increased most rapidly from 1982 to 2002. Spatially, MCIs decreased from south to north; also, high MCIs were mainly concentrated in the relatively flat areas. In addition, the partial spatial changes of MCIs had clear geographical characteristics, with the largest change in Henan Province.

Multiple standards of aging: gender-specific age stereotypes in different life domains.

Science.gov (United States)

Kornadt, Anna E; Voss, Peggy; Rothermund, Klaus

2013-12-01

Whereas it is often stated that aging might have more negative consequences for the evaluation of women compared to men, evidence for this assumption is mixed. We took a differentiated look at age stereotypes of men and women, assuming that the life domain in which older persons are rated moderates gender differences in age stereotypes. A sample of 298 participants aged 20-92 rated 65 - year-old men and women on evaluative statements in eight different life domains. Furthermore, perceptions of gender- and domain-specific age-related changes were assessed by comparing the older targets to 45 - year-old men and women, respectively. The results speak in favor of the domain specificity of evaluative asymmetries in age stereotypes for men and women, and imply that an understanding of gendered perceptions of aging requires taking into account the complexities of domain-specific views on aging.

Conserved Domain Database (CDD)

Data.gov (United States)

U.S. Department of Health & Human Services — CDD is a protein annotation resource that consists of a collection of well-annotated multiple sequence alignment models for ancient domains and full-length proteins.

Domain-Specific Multimodeling

DEFF Research Database (Denmark)

Hessellund, Anders

the overall level of abstraction. It does, however, also introduce a new problem of coordinating multiple different languages in a single system. We call this problem the coordination problem. In this thesis, we present the coordination method for domain-specific multimodeling that explicitly targets...

Autographa californica multiple nucleopolyhedrovirus GP64 protein: Analysis of domain I and V amino acid interactions and membrane fusion activity

Energy Technology Data Exchange (ETDEWEB)

Yu, Qianlong [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China); Blissard, Gary W. [Boyce Thompson Institute, Cornell University, Ithaca, NY 14853, United State (United States); Liu, Tong-Xian [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China); Li, Zhaofei, E-mail: zhaofeili73@outlook.com [State Key Laboratory of Crop Stress Biology for Arid Areas, Key Laboratory of Northwest Loess Plateau Crop Pest Management of Ministry of Agriculture, College of Plant Protection, Northwest A& F University, Yangling, Shaanxi 712100 (China)

2016-01-15

The Autographa californica multiple nucleopolyhedrovirus GP64 is a class III viral fusion protein. Although the post-fusion structure of GP64 has been solved, its pre-fusion structure and the detailed mechanism of conformational change are unknown. In GP64, domain V is predicted to interact with two domain I segments that flank fusion loop 2. To evaluate the significance of the amino acids involved in these interactions, we examined 24 amino acid positions that represent interacting and conserved residues within domains I and V. In several cases, substitution of a single amino acid involved in a predicted interaction disrupted membrane fusion activity, but no single amino acid pair appears to be absolutely required. We identified 4 critical residues in domain V (G438, W439, T452, and T456) that are important for membrane fusion, and two residues (G438 and W439) that appear to be important for formation or stability of the pre-fusion conformation of GP64. - Highlights: • The baculovirus envelope glycoprotein GP64 is a class III viral fusion protein. • The detailed mechanism of conformational change of GP64 is unknown. • We analyzed 24 positions that might stabilize the post-fusion structure of GP64. • We identified 4 residues in domain V that were critical for membrane fusion. • Two residues are critical for formation of the pre-fusion conformation of GP64.

Frequency-domain and time-domain methods for feedback nonlinear systems and applications to chaos control

International Nuclear Information System (INIS)

Duan Zhisheng; Wang Jinzhi; Yang Ying; Huang Lin

2009-01-01

This paper surveys frequency-domain and time-domain methods for feedback nonlinear systems and their possible applications to chaos control, coupled systems and complex dynamical networks. The absolute stability of Lur'e systems with single equilibrium and global properties of a class of pendulum-like systems with multi-equilibria are discussed. Time-domain and frequency-domain criteria for the convergence of solutions are presented. Some latest results on analysis and control of nonlinear systems with multiple equilibria and applications to chaos control are reviewed. Finally, new chaotic oscillating phenomena are shown in a pendulum-like system and a new nonlinear system with an attraction/repulsion function.

An Exemplar-Based Multi-View Domain Generalization Framework for Visual Recognition.

Science.gov (United States)

Niu, Li; Li, Wen; Xu, Dong; Cai, Jianfei

2018-02-01

In this paper, we propose a new exemplar-based multi-view domain generalization (EMVDG) framework for visual recognition by learning robust classifier that are able to generalize well to arbitrary target domain based on the training samples with multiple types of features (i.e., multi-view features). In this framework, we aim to address two issues simultaneously. First, the distribution of training samples (i.e., the source domain) is often considerably different from that of testing samples (i.e., the target domain), so the performance of the classifiers learnt on the source domain may drop significantly on the target domain. Moreover, the testing data are often unseen during the training procedure. Second, when the training data are associated with multi-view features, the recognition performance can be further improved by exploiting the relation among multiple types of features. To address the first issue, considering that it has been shown that fusing multiple SVM classifiers can enhance the domain generalization ability, we build our EMVDG framework upon exemplar SVMs (ESVMs), in which a set of ESVM classifiers are learnt with each one trained based on one positive training sample and all the negative training samples. When the source domain contains multiple latent domains, the learnt ESVM classifiers are expected to be grouped into multiple clusters. To address the second issue, we propose two approaches under the EMVDG framework based on the consensus principle and the complementary principle, respectively. Specifically, we propose an EMVDG_CO method by adding a co-regularizer to enforce the cluster structures of ESVM classifiers on different views to be consistent based on the consensus principle. Inspired by multiple kernel learning, we also propose another EMVDG_MK method by fusing the ESVM classifiers from different views based on the complementary principle. In addition, we further extend our EMVDG framework to exemplar-based multi-view domain

MOTORES DE COMBUSTIÓN INTERNA (MCI OPERANDO CON MEZCLAS DE ETANOL GASOLINA: REVISIÓN

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Alexander García Mariaca

2016-01-01

Full Text Available En este artículo se presenta una revisión bibliográfica acerca del uso de etanol como combustible en motores de combustión interna de encendido provocado (MCI-EP. Este empieza por una breve descripción de las diversas formas de producción y principales productores en el mundo de etanol, para posteriormente profundizar en el desempeño, combustión y las emisiones en MCIEP al operar con diferentes mezclas de etanol y gasolina convencional. Los resultados obtenidos por los diferentes autores de los parámetros de desempeño, combustión y emisiones, como potencia, torque, presión media efectiva al freno (BME, eficiencia térmica, tasa de liberación de calor, eficiencia de combustión, presión en la cámara de combustión y emisiones reguladas (NOx, THC, CO, CO2 y MP, muestran que el etanol es un excelente comburente para utilizarse en mezcla con gasolina, especialmente en relaciones superiores al 20 % en volumen (E20; debido a que se produce un mejor proceso de combustión causado por el aumento en la cantidad de oxígeno, y se logran así mejoras en los parámetros de desempeño y emisiones del MCI, tales como incrementos en la potencia y la eficiencia térmica y disminución de las emisiones de CO y THC. Sin embargo, se generan aumentos en algunas emisiones contaminantes, como el CO2 y los NOx causados por el exceso de oxígeno en la combustión y el incremento de la temperatura de los gases de escape.

Sensitivities and detection limits of X-ray fluorescence analysis with a 10 mCi241Am source

International Nuclear Information System (INIS)

Wundt, K.; Janghorbani, M.; Starke, K.

1976-01-01

Seven trace elements ranging from chromium to barium were preconcentrated on Amberlite IR-120 cation exchange paper and determined in an energy dispersive X-ray fluorescence system using a 10 mCi 241 Am source. Sensitivities were experimentally determined and checked with theoretically calculated values. The detection limits are compared with elemental levels present in typical surface waters and those allowed in drinking water. Appropriate conclusions as to feasibility of such a system for environmental monitoring are drawn. (orig.) [de

Performance Analysis of Multiple Wave Energy Converters Placed on a Floating Platform in the Frequency Domain

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Hyebin Lee

2018-02-01

Full Text Available Wind-wave hybrid power generation systems have the potential to become a significant source of affordable renewable energy. However, their strong interactions with both wind- and wave-induced forces raise a number of technical challenges for modelling. The present study undertakes a numerical investigation on multi-body hydrodynamic interaction between a wind-wave hybrid floating platform and multiple wave energy converters (WECs in a frequency domain. In addition to the exact responses of the platform and the WECs, the power take-off (PTO mechanism was taken into account for analysis. The coupled hydrodynamic coefficients and wave exciting forces were obtained from WAMIT, the 3D diffraction/radiation solver based on the boundary element method. The overall performance of the multiple WECs is presented and compared with the performance of a single isolated WEC. The analysis showed significant differences in the dynamic responses of the WECs when the multi-body interaction was considered. In addition, the PTO damping effect made a considerable difference to the responses of the WECs. However, the platform response was only minimally affected by PTO damping. With regard to energy capture, the interaction effect of the designed multiple WEC array layout is evaluated. The WEC array configuration showed both constructive and destructive effects in accordance with the incident wave frequency and direction.

Preclinical Polymodal Hallucinations for 13 Years before Dementia with Lewy Bodies

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Carlo Abbate

2014-01-01

Full Text Available Objective. We describe a case of dementia with Lewy bodies (DLB that presented long-lasting preclinical complex polymodal hallucinations. Background. Few studies have deeply investigated the characteristics of hallucinations in DLB, especially in the preclinical phase. Moreover, the clinical phenotype of mild cognitive impairment-(MCI- DLB is poorly understood. Methods. The patient was followed for 4 years and a selective phenomenological and cognitive study was performed at the predementia stage. Results. The phenomenological study showed the presence of hypnagogic and hypnopompic hallucinations that allowed us to make a differential diagnosis between DLB and Charles Bonnet syndrome (CBS. The neuropsychological evaluation showed a multiple domain without amnesia MCI subtype with prefrontal dysexecutive, visuoperceptual, and visuospatial impairments and simultanagnosia, which has not previously been reported in MCI-DLB. Conclusions. This study extends the prognostic value of hallucinations for DLB to the preclinical phases. It supports and refines the MCI-DLB concept and identifies simultanagnosia as a possible early cognitive marker. Finally, it confirms an association between hallucinations and visuoperceptual impairments at an intermediate stage of the disease course and strongly supports the hypothesis that hallucinations in the earliest stages of DLB may reflect a narcolepsy-like REM-sleep disorder.

Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images

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Shengwen Guo

2017-05-01

Full Text Available Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI. Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI, the converted MCI (cMCI, and the normal control (NC groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM. An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI–cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI–NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI–NC comparison. The best performances obtained by the SVM classifier using the essential features were 5–40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and

Radioiodine therapy of differentiated thyroid cancer: radiologic impact of out-patient treatment with 100 to 150 mCi Iodine-131 activities; Radioiodoterapia do carcinoma diferenciado da tireoide: impacto radiologico da liberacao hospitalar de pacientes com atividades entre 100 e 150 mCi de iodo-131

Energy Technology Data Exchange (ETDEWEB)

Sapienza, Marcelo Tatit; Willegaignon, Jose; Ono, Carla Rachel; Watanabe, Tomoco; Guimaraes, Maria Ines Calil Cury; Buchpiguel, Carlos Alberto [Universidade de Sao Paulo (USP), SP (Brazil). Faculdade de Medicina. Servico de Medicina Nuclear; Gutterres, Ricardo Fraga; Marechal, Maria Helena da Hora [Comissao Nacional de Energia Nuclear (CNEN), Rio de Janeiro, RJ (Brazil)

2009-07-01

Purpose: To evaluate exposure and dosimetry to family members and environment due to outpatient radioiodine therapy of differentiated thyroid carcinoma. Methods: Twenty patients were treated with 100-150 mCi of iodine-131 on an out-patient basis. Family members dosimetry (n = 27) and potential doses inside the house were measured with thermoluminescent dosimeters. Surface contamination and radioactive wastes were also monitored. Results: Less than 1.0 mSv doses were found in 26 co-habitants and 2.8 mSv in a single case (inferior to the acceptable value of 5.0 mSv/procedure). Potential doses in the houses were inferior to 0.25 mSv, excluding the patients bedroom (mean value = 0.69 mSv). Surface contamination (mean = 4.2 Bq.cm{sup -2}) were below clearance levels. Radioactive wastes generated had a volume of 2.5 liters and a total activity estimated in 90 {mu}Ci, with a calculated exposure close to the background radiation levels. Conclusions: No radiological impact was detected after iodine therapy with 100-150 mCi on an out-patient basis followed by experienced professionals. (author)

Abstract Word Definition in Patients with Amnestic Mild Cognitive Impairment

Science.gov (United States)

Kim, Soo Ryon; Baek, Min Jae; Kim, HyangHee

2015-01-01

The aims of this study were to investigate concrete and abstract word definition ability (1) between patients with amnestic mild cognitive impairment (aMCI) and normal adults and (2) between the aMCI subtypes (i.e., amnestic single-domain MCI and amnestic multidomain MCI; asMCI and amMCI) and normal controls. The 68 patients with aMCI (29 asMCI and 39 amMCI) and 93 age- and education-matched normal adults performed word definition tasks composed of five concrete (e.g., train) and five abstract nouns (e.g., jealousy). Task performances were analyzed on total score, number of core meanings, and number of supplementary meanings. The results were as follows. First, the aMCI patients scored significantly poorer than the normal controls in only abstract word definition. Second, both subtypes of aMCI performed worse than the controls in only abstract word definition. In conclusion, a definition task of abstract rather than concrete concepts may provide richer information to show semantic impairment of aMCI. PMID:26347214

Abstract Word Definition in Patients with Amnestic Mild Cognitive Impairment

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Soo Ryon Kim

2015-01-01

Full Text Available The aims of this study were to investigate concrete and abstract word definition ability (1 between patients with amnestic mild cognitive impairment (aMCI and normal adults and (2 between the aMCI subtypes (i.e., amnestic single-domain MCI and amnestic multidomain MCI; asMCI and amMCI and normal controls. The 68 patients with aMCI (29 asMCI and 39 amMCI and 93 age- and education-matched normal adults performed word definition tasks composed of five concrete (e.g., train and five abstract nouns (e.g., jealousy. Task performances were analyzed on total score, number of core meanings, and number of supplementary meanings. The results were as follows. First, the aMCI patients scored significantly poorer than the normal controls in only abstract word definition. Second, both subtypes of aMCI performed worse than the controls in only abstract word definition. In conclusion, a definition task of abstract rather than concrete concepts may provide richer information to show semantic impairment of aMCI.

Detecting atypical examples of known domain types by sequence similarity searching: the SBASE domain library approach.

Science.gov (United States)

Dhir, Somdutta; Pacurar, Mircea; Franklin, Dino; Gáspári, Zoltán; Kertész-Farkas, Attila; Kocsor, András; Eisenhaber, Frank; Pongor, Sándor

2010-11-01

SBASE is a project initiated to detect known domain types and predicting domain architectures using sequence similarity searching (Simon et al., Protein Seq Data Anal, 5: 39-42, 1992, Pongor et al, Nucl. Acids. Res. 21:3111-3115, 1992). The current approach uses a curated collection of domain sequences - the SBASE domain library - and standard similarity search algorithms, followed by postprocessing which is based on a simple statistics of the domain similarity network (http://hydra.icgeb.trieste.it/sbase/). It is especially useful in detecting rare, atypical examples of known domain types which are sometimes missed even by more sophisticated methodologies. This approach does not require multiple alignment or machine learning techniques, and can be a useful complement to other domain detection methodologies. This article gives an overview of the project history as well as of the concepts and principles developed within this the project.

High Levels of Antibodies to Multiple Domains and Strains of VAR2CSA Correlate with the Absence of Placental Malaria in Cameroonian Women Living in an Area of High Plasmodium falciparum Transmission

Science.gov (United States)

Tutterrow, Yeung L.; Avril, Marion; Singh, Kavita; Long, Carole A.; Leke, Robert J.; Sama, Grace; Salanti, Ali; Smith, Joseph D.; Leke, Rose G. F.

2012-01-01

Placental malaria, caused by sequestration of Plasmodium falciparum-infected erythrocytes in the placenta, is associated with increased risk of maternal morbidity and poor birth outcomes. The parasite antigen VAR2CSA (variant surface antigen 2-chondroitin sulfate A) is expressed on infected erythrocytes and mediates binding to chondroitin sulfate A, initiating inflammation and disrupting homeostasis at the maternal-fetal interface. Although antibodies can prevent sequestration, it is unclear whether parasite clearance is due to antibodies to a single Duffy binding-like (DBL) domain or to an extensive repertoire of antibodies to multiple DBL domains and allelic variants. Accordingly, plasma samples collected longitudinally from pregnant women were screened for naturally acquired antibodies against an extensive panel of VAR2CSA proteins, including 2 to 3 allelic variants for each of 5 different DBL domains. Analyses were performed on plasma samples collected from 3 to 9 months of pregnancy from women living in areas in Cameroon with high and low malaria transmission. The results demonstrate that high antibody levels to multiple VAR2CSA domains, rather than a single domain, were associated with the absence of placental malaria when antibodies were present from early in the second trimester until term. Absence of placental malaria was associated with increasing antibody breadth to different DBL domains and allelic variants in multigravid women. Furthermore, the antibody responses of women in the lower-transmission site had both lower magnitude and lesser breadth than those in the high-transmission site. These data suggest that immunity to placental malaria results from high antibody levels to multiple VAR2CSA domains and allelic variants and that antibody breadth is influenced by malaria transmission intensity. PMID:22331427

Is the Montreal Cognitive Assessment (MoCA) test better suited than the Mini-Mental State Examination (MMSE) in mild cognitive impairment (MCI) detection among people aged over 60? Meta-analysis.

Science.gov (United States)

Ciesielska, Natalia; Sokołowski, Remigiusz; Mazur, Ewelina; Podhorecka, Marta; Polak-Szabela, Anna; Kędziora-Kornatowska, Kornelia

2016-10-31

Screening tests play a crucial role in dementia diagnostics, thus they should be very sensitive for mild cognitive impairment (MCI) assessment. Nowadays, the MiniMental State Examination (MMSE) is the most commonly used scale in cognitive function evaluation, albeit it is claimed to be imprecise for MCI detection. The Montreal Cognitive Assessment (MoCA), was created as an alternative method for MMSE. Aim. MoCA vs. MMSE credibility assessment in detecting MCI, while taking into consideration the sensitivity and specificity by cut-off points. A systematic literature search was carried out by the authors using EBSCO host Web, Wiley Online Library, Springer Link, Science Direct and Medline databases. The following medical subject headings were used in the search: mild cognitive impairment, mini-mental state examination, Montreal cognitive assessment, diagnostics value. Papers which met inclusion and exclusion criteria were chosen to be included in this review. At the end, for the evaluation of MoCA 20, and MMSE 13 studies were qualified. Research credibility was established by computing weighted arithmetic mean, where weight is defined as population for which the result of sensitivity and specificity for the cut-off point was achieved. The cut-offs are shown as ROC curve and accuracy of diagnosis for MoCA and MMSE was calculated as the area under the curve (AUC). ROC curve analysis for MoCA demonstrated that MCI best detection can be achieved with a cut-off point of 24/25 (n = 9350, the sensitivity of 80.48% and specificity of 81.19%). AUC was 0.846 (95% CI 0.823-0.868). For MMSE, it turned out that more important cut-off was of 27/28 (n = 882, 66.34% sensitivity and specificity of 72.94%). AUC was 0.736 (95% CI 0.718-0.767). MoCA test better meets the criteria for screening tests for the detection of MCI among patients over 60 years of age than MMSE.

Knowing, Applying, and Reasoning about Arithmetic: Roles of Domain-General and Numerical Skills in Multiple Domains of Arithmetic Learning

Science.gov (United States)

Zhang, Xiao; Räsänen, Pekka; Koponen, Tuire; Aunola, Kaisa; Lerkkanen, Marja-Kristiina; Nurmi, Jari-Erik

2017-01-01

The longitudinal relations of domain-general and numerical skills at ages 6-7 years to 3 cognitive domains of arithmetic learning, namely knowing (written computation), applying (arithmetic word problems), and reasoning (arithmetic reasoning) at age 11, were examined for a representative sample of 378 Finnish children. The results showed that…

High-multiplicity processes

International Nuclear Information System (INIS)

Shelkov, G.; Sisakyan, A.; Mandzhavidze, I.

1999-01-01

We wish to demonstrate that investigation of asymptotically high multiplicity (AHM) hadron reactions may solve, or at least clear up, a number of problems unsolvable by other ways. We would lean upon the idea: (i) the reactions final state entropy is proportional to multiplicity and, by this reason, just in the AHM domain one may expect the equilibrium final state and (ii) the AHM final state is cold because of the energy-momentum conservation laws. This means that the collective phenomena may become important in the AHM domain. The possibility of hard processes dominance is considered also

Effects of bilingualism on the age of onset and progression of MCI and AD: evidence from executive function tests.

Science.gov (United States)

Bialystok, Ellen; Craik, Fergus I M; Binns, Malcolm A; Ossher, Lynn; Freedman, Morris

2014-03-01

Previous articles have reported that bilingualism is associated with a substantial delay in the onset of both Alzheimer's disease (AD) and Mild Cognitive Impairment (MCI). The present study reports results from 74 MCI patients and 75 AD patients; approximately half of the patients in each group were bilingual. All patients were interviewed to obtain details of their language use, onset of their condition, and lifestyle habits. Patients performed three executive function (EF) tests from the D-KEFS battery (Trails, Color-Word Interference, Verbal Fluency) on 3 occasions over a period of approximately 1 year. Results replicated the finding that bilingual patients are several years older than comparable monolinguals at both age of symptom onset and date of first clinic visit. This result could not be attributed to language group differences in such lifestyle variables as diet, smoking, alcohol consumption, physical activity, or social activity. On the first testing occasion, performance on the EF tasks was generally comparable between the language groups, contesting arguments that bilinguals wait longer before attending the clinic. Finally, EF performance tended to decline over the 3 sessions, but no differences were found between monolinguals and bilinguals in the rate of decline. PsycINFO Database Record (c) 2014 APA, all rights reserved.

The epidemiology of mild cognitive impairment (MCI and Alzheimer’s disease (AD in community-living seniors: protocol of the MemoVie cohort study, Luxembourg

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Perquin Magali

2012-07-01

Full Text Available Abstract Background Cognitive impairment and Alzheimer’s disease (AD are increasingly considered a major public health problem. The MemoVie cohort study aims to investigate the living conditions or risk factors under which the normal cognitive capacities of the senior population in Luxembourg (≥ 65 year-old evolve (1 to mild cognitive impairment (MCI – transitory non-clinical stage – and (2 to AD. Identifying MCI and AD predictors undeniably constitutes a challenge in public health in that it would allow interventions which could protect or delay the occurrence of cognitive disorders in elderly people. In addition, the MemoVie study sets out to generate hitherto unavailable data, and a comprehensive view of the elderly population in the country. Methods/design The study has been designed with a view to highlighting the prevalence in Luxembourg of MCI and AD in the first step of the survey, conducted among participants selected from a random sample of the general population. A prospective cohort is consequently set up in the second step, and appropriate follow-up of the non-demented participants allows improving the knowledge of the preclinical stage of MCI. Case-control designs are used for cross-sectional or retrospective comparisons between outcomes and biological or clinical factors. To ensure maximal reliability of the information collected, we decided to opt for structured face to face interviews. Besides health status, medical and family history, demographic and socio-cultural information are explored, as well as education, habitat network, social behavior, leisure and physical activities. As multilingualism is expected to challenge the cognitive alterations associated with pathological ageing, it is additionally investigated. Data relative to motor function, including balance, walk, limits of stability, history of falls and accidents are further detailed. Finally, biological examinations, including ApoE genetic polymorphism are

Generalized Sudan's List Decoding for Order Domain Codes

DEFF Research Database (Denmark)

Geil, Hans Olav; Matsumoto, Ryutaroh

2007-01-01

We generalize Sudan's list decoding algorithm without multiplicity to evaluation codes coming from arbitrary order domains. The number of correctable errors by the proposed method is larger than the original list decoding without multiplicity....

TCMB’nin Para Politikası Duruşunun Alternatif Açıklaması: Parasal Durum Endeksi (MCI (Alternative Explanations for the Monetary Stance of CBRT: Monetary Condition Index (MCI

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Bora SÜSLÜ

2012-01-01

Full Text Available Knowledge of economic agent’s expectations enables the policy authorities to evaluate responsiveness of economic and political decisions. Hence, all central banks in the World including the Central Bank of Republic of Turkey (CBRT want to know public expectations and re-use this knowledge to influence expectations of people especially in implementing interest rate as an instrument. However, considering the stability of economy, central banks try to take into account real variables which are more flexible and effective as policy tools. Moreover, real variables are directly related to welfare of the society.The main aim of this study is to investigate whether the monetary stance of CBRT that bases on policy rules takes into account aggregate demand that impacts growth and price level during past decade. The study employs ARDL approach using time series data obtained from CBRT. The results indicate that CBRT was heavily relied on Monetary Condition Index (MCI over the past decade contrary to its official discourse.

The trajectory of cognitive decline in the pre-dementia phase in memory clinic visitors: findings from the 4C-MCI study

NARCIS (Netherlands)

Hamel, R.; Kohler, S.; Sistermans, N.; Koene, T.; Pijnenburg, Y.; van der Flier, W.M.; Scheltens, P.; Aalten, P.; Verhey, F.; Visser, P.J.; Ramakers, I.

2015-01-01

Background We investigated the course of decline in multiple cognitive domains in non-demented subjects from a memory clinic setting, and compared pattern, onset and magnitude of decline between subjects who progressed to Alzheimer's disease (AD) dementia at follow-up and subjects who did not

Comparison of different methods of spatial normalization of FDG-PET brain images in the voxel-wise analysis of MCI patients and controls

International Nuclear Information System (INIS)

Martino, M.E.; Villoria, J.G. de; Lacalle-Aurioles, M.; Olazaran, J.; Navarro, E.; Desco, M.; Cruz, I.; Garcia-Vazquez, V.; Carreras, J.L.

2013-01-01

One of the most interesting clinical applications of 18F-fluorodexyglucose (FDG) positron emission tomography (PET) imaging in neurodegenerative pathologies is that of establishing the prognosis of patients with mild cognitive impairment (MCI), some of whom have a high risk of progressing to Alzheimer's disease (AD). One method of analyzing these images is to perform statistical parametric mapping (SPM) analysis. Spatial normalization is a critical step in such an analysis. The purpose of this study was to assess the effect of using different methods of spatial normalization on the results of SPM analysis of 18F-FDG PET images by comparing patients with MCI and controls. We evaluated the results of three spatial normalization methods in an SPM analysis by comparing patients diagnosed with MCI with a group of control subjects. We tested three methods of spatial normalization: MRI-diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL) and MRI-SPM8, which combine structural and functional images, and FDG-SPM8, which is based on the functional images only. The results obtained with the three methods were consistent in terms of the main pattern of functional alterations detected; namely, a bilateral reduction in glucose metabolism in the frontal and parietal cortices in the patient group. However, MRI-SPM8 also revealed differences in the left temporal cortex, and MRI-DARTEL revealed further differences in the left temporal cortex, precuneus, and left posterior cingulate. The results obtained with MRI-DARTEL were the most consistent with the pattern of changes in AD. When we compared our observations with those of previous reports, MRI-SPM8 and FDG-SPM8 seemed to show an incomplete pattern. Our results suggest that basing the spatial normalization method on functional images only can considerably impair the results of SPM analysis of 18F-FDG PET studies. (author)

MrTADFinder: A network modularity based approach to identify topologically associating domains in multiple resolutions.

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Koon-Kiu Yan

2017-07-01

Full Text Available Genome-wide proximity ligation based assays such as Hi-C have revealed that eukaryotic genomes are organized into structural units called topologically associating domains (TADs. From a visual examination of the chromosomal contact map, however, it is clear that the organization of the domains is not simple or obvious. Instead, TADs exhibit various length scales and, in many cases, a nested arrangement. Here, by exploiting the resemblance between TADs in a chromosomal contact map and densely connected modules in a network, we formulate TAD identification as a network optimization problem and propose an algorithm, MrTADFinder, to identify TADs from intra-chromosomal contact maps. MrTADFinder is based on the network-science concept of modularity. A key component of it is deriving an appropriate background model for contacts in a random chain, by numerically solving a set of matrix equations. The background model preserves the observed coverage of each genomic bin as well as the distance dependence of the contact frequency for any pair of bins exhibited by the empirical map. Also, by introducing a tunable resolution parameter, MrTADFinder provides a self-consistent approach for identifying TADs at different length scales, hence the acronym "Mr" standing for Multiple Resolutions. We then apply MrTADFinder to various Hi-C datasets. The identified domain boundaries are marked by characteristic signatures in chromatin marks and transcription factors (TF that are consistent with earlier work. Moreover, by calling TADs at different length scales, we observe that boundary signatures change with resolution, with different chromatin features having different characteristic length scales. Furthermore, we report an enrichment of HOT (high-occupancy target regions near TAD boundaries and investigate the role of different TFs in determining boundaries at various resolutions. To further explore the interplay between TADs and epigenetic marks, as tumor mutational

Utility and limitations of Addenbrooke's Cognitive Examination-Revised for detecting mild cognitive impairment in Parkinson's disease.

Science.gov (United States)

Komadina, Natalie C; Terpening, Zoe; Huang, Yue; Halliday, Glenda M; Naismith, Sharon L; Lewis, Simon J G

2011-01-01

To evaluate the utility of the Addenbrooke's Cognitive Examination-Revised (ACE-R) as a screening tool for mild cognitive impairment in Parkinson's disease (PD-MCI). PD patients underwent comprehensive neuropsychological and neurological evaluations and ACE-R assessment. The ACE-R was superior to the Mini-Mental State Exam (MMSE) in detecting PD-MCI, with a cutoff score of ≤93 offering a sensitivity of 61% and a specificity of 64%. The utility of the ACE-R in detecting PD-MCI is largely influenced by the fluency sub-domain score, and has optimal discriminability when utilized in patients with lower levels of education (≤12 years of formal schooling). The ACE-R must be used cautiously as a screening tool for PD-MCI, with results being most influenced by its fluency sub-domain score and patient education levels. Copyright © 2011 S. Karger AG, Basel.

Database Concepts in a Domain Ontology

Directory of Open Access Journals (Sweden)

Gorskis Henrihs

2017-12-01

Full Text Available There are multiple approaches for mapping from a domain ontology to a database in the task of ontology-based data access. For that purpose, external mapping documents are most commonly used. These documents describe how the data necessary for the description of ontology individuals and other values, are to be obtained from the database. The present paper investigates the use of special database concepts. These concepts are not separated from the domain ontology; they are mixed with domain concepts to form a combined application ontology. By creating natural relationships between database concepts and domain concepts, mapping can be implemented more easily and with a specific purpose. The paper also investigates how the use of such database concepts in addition to domain concepts impacts ontology building and data retrieval.

Physical activity domains and cognitive function over three years in older adults with subjective memory complaints: Secondary analysis from the MAPT trial.

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de Souto Barreto, Philipe; Andrieu, Sandrine; Rolland, Yves; Vellas, Bruno

2018-01-01

We aimed to examine the associations of physical activity (PA) domains (i.e., PA in leisure-time (LTPA), for housework (HPA), or for gardening (GPA)) with cognitive function in older adults with subjective memory complaints (no-dementia) and to investigate if those associations were dependent on the status of apolipoprotein E allele 4 (APOE4), omega-3 levels and mild cognitive impairment (MCI). Observational prospective secondary analysis using longitudinal data from a randomized controlled trial. Participants were 420 French community-dwelling people (aged 75.6±4.4; 66.4% women) randomized into the placebo group. They were assessed at baseline, 6-, 12-, 24- and 36-month using a battery of neuropsychological tests; a composite cognitive Z score was elaborated for all time points. Data on PA come from baseline and was obtained using a self-reported questionnaire. In time-adjusted analysis, LTPA significantly predicted cognitive function over three years for almost all tests and the composite Z score, with higher LTPA associated with better function; multivariate analysis showed a significant association only for verbal fluency. HPA was not associated to cognitive function, whereas GPA had mixed results. The magnitude of the PA-cognition associations was very weak, being the strongest for LTPA. Stratified analyses showed that the associations between PA and cognitive function were stronger for MCI, people with normal omega-3 index levels, and APOE4 non-carriers. PA domain is an important aspect to take into account when examining the associations between PA and cognitive function. Biomarkers of cognitive function may modulate the PA-cognition associations. Copyright © 2017 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

When it comes to lifestyle recommendations, more is sometimes less: a meta-analysis of theoretical assumptions underlying the effectiveness of interventions promoting multiple behavior domain change.

Science.gov (United States)

Wilson, Kristina; Senay, Ibrahim; Durantini, Marta; Sánchez, Flor; Hennessy, Michael; Spring, Bonnie; Albarracín, Dolores

2015-03-01

A meta-analysis of 150 research reports summarizing the results of multiple behavior domain interventions examined theoretical predictions about the effects of the included number of recommendations on behavioral and clinical change in the domains of smoking, diet, and physical activity. The meta-analysis yielded 3 main conclusions. First, there is a curvilinear relation between the number of behavioral recommendations and improvements in behavioral and clinical measures, with a moderate number of recommendations producing the highest level of change. A moderate number of recommendations is likely to be associated with stronger effects because the intervention ensures the necessary level of motivation to implement the recommended changes, thereby increasing compliance with the goals set by the intervention, without making the intervention excessively demanding. Second, this curve was more pronounced when samples were likely to have low motivation to change, such as when interventions were delivered to nonpatient (vs. patient) populations, were implemented in nonclinic (vs. clinic) settings, used lay community (vs. expert) facilitators, and involved group (vs. individual) delivery formats. Finally, change in behavioral outcomes mediated the effects of number of recommended behaviors on clinical change. These findings provide important insights that can help guide the design of effective multiple behavior domain interventions. PsycINFO Database Record (c) 2015 APA, all rights reserved.

When It Comes to Lifestyle Recommendations, More is Sometimes Less: A Meta-Analysis of Theoretical Assumptions Underlying the Effectiveness of Interventions Promoting Multiple Behavior Domain Change

Science.gov (United States)

Wilson, Kristina; Senay, Ibrahim; Durantini, Marta; Sánchez, Flor; Hennessy, Michael; Spring, Bonnie; Albarracín, Dolores

2016-01-01

A meta-analysis of 150 research reports summarizing the results of multiple behavior domain interventions examined theoretical predictions about the effects of the included number of recommendations on behavioral and clinical change in the domains of smoking, diet, and physical activity. The meta-analysis yielded three main conclusions. First, there is a curvilinear relation between the number of behavioral recommendations and improvements in behavioral and clinical measures, with a moderate number of recommendations producing the highest level of change. A moderate number of recommendations is likely to be associated with stronger effects because the intervention ensures the necessary level of motivation to implement the recommended changes, thereby increasing compliance with the goals set by the intervention, without making the intervention excessively demanding. Second, this curve was more pronounced when samples were likely to have low motivation to change, such as when interventions were delivered to non-patient (vs. patient) populations, were implemented in non-clinic (vs. clinic) settings, used lay community (vs. expert) facilitators, and involved group (vs. individual) delivery formats. Finally, change in behavioral outcomes mediated the effects of number of recommended behaviors on clinical change. These findings provide important insights that can help guide the design of effective multiple behavior domain interventions. PMID:25528345

Delusional disorder and schizophrenia: a comparative study across multiple domains.

Science.gov (United States)

Peralta, V; Cuesta, M J

2016-10-01

Delusional disorder (DD) is an under-researched condition and its relationship to schizophrenia (SZ) controversial. This study aimed to further characterize DD and to examine multi-domain evidence for the distinction between DD and SZ. Using univariate analyses we examined 146 subjects with DD, 114 subjects with paranoid SZ and 244 subjects with non-paranoid SZ on 52 characteristics from several domains including demographics, risk factors, premorbid features, illness characteristics, index episode features, delusional-related features, response to treatment and outcome. In a further step, we searched for independent associations of the examined characteristics with DD v. SZ. Univariate analyses showed that DD differed from either form of SZ in 40 characteristics, the pattern of findings indicated that paranoid SZ was much more similar to non-paranoid SZ than DD. Relative to subjects with SZ, those with DD were more likely to have drug abuse before illness onset, better premorbid sexual adjustment, later age at illness onset, higher levels of affective symptoms and lack of insight, poorer response to antipsychotic medication, better functioning in the domains of personal care, paid work and social functioning; last, subjects with DD had fewer but more severe delusions and higher ratings of conviction of delusional experience than those with SZ. Predominance of jealousy and somatic delusions was confined to subjects with DD. DD and SZ represent two distinct classes of disorders, the differential features of DD being of nosological, aetiological and therapeutic relevance.

Multiplicative properties of quantum channels

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Rahaman, Mizanur

2017-08-01

In this paper, we study the multiplicative behaviour of quantum channels, mathematically described by trace preserving, completely positive maps on matrix algebras. It turns out that the multiplicative domain of a unital quantum channel has a close connection to its spectral properties. A structure theorem (theorem 2.5), which reveals the automorphic property of an arbitrary unital quantum channel on a subalgebra, is presented. Various classes of quantum channels (irreducible, primitive, etc) are then analysed in terms of this stabilising subalgebra. The notion of the multiplicative index of a unital quantum channel is introduced, which measures the number of times a unital channel needs to be composed with itself for the multiplicative algebra to stabilise. We show that the maps that have trivial multiplicative domains are dense in completely bounded norm topology in the set of all unital completely positive maps. Some applications in quantum information theory are discussed.

Mild cognitive impairment and deficits in instrumental activities of daily living: a systematic review

NARCIS (Netherlands)

Jekel, K.; Damian, M.; Wattmo, C.; Hausner, L.; Bullock, R.; Connelly, P.J.; Dubois, B.; Eriksdotter, M.; Ewers, M.; Graessel, E.; Kramberger, M.G.; Law, E.; Mecocci, P.; Molinuevo, J.L.; Nygard, L.; Olde Rikkert, M.G.M.; Orgogozo, J.M.; Pasquier, F.; Peres, K.; Salmon, E.; Sikkes, S.A.; Sobow, T.; Spiegel, R.; Tsolaki, M.; Winblad, B.; Frolich, L.

2015-01-01

INTRODUCTION: There is a growing body of evidence that subtle deficits in instrumental activities of daily living (IADL) may be present in mild cognitive impairment (MCI). However, it is not clear if there are IADL domains that are consistently affected across patients with MCI. In this systematic

Multiple constant multiplication optimizations for field programmable gate arrays

CERN Document Server

Kumm, Martin

2016-01-01

This work covers field programmable gate array (FPGA)-specific optimizations of circuits computing the multiplication of a variable by several constants, commonly denoted as multiple constant multiplication (MCM). These optimizations focus on low resource usage but high performance. They comprise the use of fast carry-chains in adder-based constant multiplications including ternary (3-input) adders as well as the integration of look-up table-based constant multipliers and embedded multipliers to get the optimal mapping to modern FPGAs. The proposed methods can be used for the efficient implementation of digital filters, discrete transforms and many other circuits in the domain of digital signal processing, communication and image processing. Contents Heuristic and ILP-Based Optimal Solutions for the Pipelined Multiple Constant Multiplication Problem Methods to Integrate Embedded Multipliers, LUT-Based Constant Multipliers and Ternary (3-Input) Adders An Optimized Multiple Constant Multiplication Architecture ...

Influence of Different Cut-Off Values on the Diagnosis of Mild Cognitive Impairment in Parkinson's Disease

Directory of Open Access Journals (Sweden)

Inga Liepelt-Scarfone

2011-01-01

Full Text Available Comparable to Alzheimer's disease, mild cognitive impairment in Parkinson's disease (PD-MCI is associated with an increased risk for dementia. However different definitions of PD-MCI may have varying predictive accuracy for dementia. In a cohort of 101 nondemented Parkinson patients who underwent neuropsychological testing, the frequency of PD-MCI subjects and PD-MCI subtypes (i.e., amnestic/nonamnestic was determined by use of varying healthy population-based cut-off values. We also investigated the association between defined PD-MCI groups and ADL scales. Varying cut-off values for the definition of PD-MCI were found to affect frequency of PD-MCI subjects (9.9%–92.1% and, maybe more important, lead to a “shift” of proportion of detected PD-MCI subtypes especially within the amnestic single-domain subtype. Models using a strict cut-off value were significantly associated with lower ADL scores. Thus, the use of defined cut-off values for the definition of PD-MCI is highly relevant for comparison purposes. Strict cut-off values may have a higher predictive value for dementia.

The Aerobic and Cognitive Exercise Study (ACES for Community-Dwelling Older Adults With or At-Risk for Mild Cognitive Impairment (MCI: Neuropsychological, Neurobiological and Neuroimaging Outcomes of a Randomized Clinical Trial

Directory of Open Access Journals (Sweden)

Cay Anderson-Hanley

2018-05-01

Full Text Available Prior research has found that cognitive benefits of physical exercise and brain health in older adults may be enhanced when mental exercise is interactive simultaneously, as in exergaming. It is unclear whether the cognitive benefit can be maximized by increasing the degree of mental challenge during exercise. This randomized clinical trial (RCT, the Aerobic and Cognitive Exercise Study (ACES sought to replicate and extend prior findings of added cognitive benefit from exergaming to those with or at risk for mild cognitive impairment (MCI. ACES compares the effects of 6 months of an exer-tour (virtual reality bike rides with the effects of a more effortful exer-score (pedaling through a videogame to score points. Fourteen community-dwelling older adults meeting screening criteria for MCI (sMCI were adherent to their assigned exercise for 6 months. The primary outcome was executive function, while secondary outcomes included memory and everyday cognitive function. Exer-tour and exer-score yielded significant moderate effects on executive function (Stroop A/C; d's = 0.51 and 0.47; there was no significant interaction effect. However, after 3 months the exer-tour revealed a significant and moderate effect, while exer-score showed little impact, as did a game-only condition. Both exer-tour and exer-score conditions also resulted in significant improvements in verbal memory. Effects appear to generalize to self-reported everyday cognitive function. Pilot data, including salivary biomarkers and structural MRI, were gathered at baseline and 6 months; exercise dose was associated with increased BDNF as well as increased gray matter volume in the PFC and ACC. Improvement in memory was associated with an increase in the DLPFC. Improved executive function was associated with increased expression of exosomal miRNA-9. Interactive physical and cognitive exercise (both high and low mental challenge yielded similarly significant cognitive benefit for adherent sMCI

The Aerobic and Cognitive Exercise Study (ACES) for Community-Dwelling Older Adults With or At-Risk for Mild Cognitive Impairment (MCI): Neuropsychological, Neurobiological and Neuroimaging Outcomes of a Randomized Clinical Trial.

Science.gov (United States)

Anderson-Hanley, Cay; Barcelos, Nicole M; Zimmerman, Earl A; Gillen, Robert W; Dunnam, Mina; Cohen, Brian D; Yerokhin, Vadim; Miller, Kenneth E; Hayes, David J; Arciero, Paul J; Maloney, Molly; Kramer, Arthur F

2018-01-01

Prior research has found that cognitive benefits of physical exercise and brain health in older adults may be enhanced when mental exercise is interactive simultaneously, as in exergaming. It is unclear whether the cognitive benefit can be maximized by increasing the degree of mental challenge during exercise. This randomized clinical trial (RCT), the Aerobic and Cognitive Exercise Study (ACES) sought to replicate and extend prior findings of added cognitive benefit from exergaming to those with or at risk for mild cognitive impairment (MCI). ACES compares the effects of 6 months of an exer-tour (virtual reality bike rides) with the effects of a more effortful exer-score (pedaling through a videogame to score points). Fourteen community-dwelling older adults meeting screening criteria for MCI (sMCI) were adherent to their assigned exercise for 6 months. The primary outcome was executive function, while secondary outcomes included memory and everyday cognitive function. Exer-tour and exer-score yielded significant moderate effects on executive function (Stroop A/C; d 's = 0.51 and 0.47); there was no significant interaction effect. However, after 3 months the exer-tour revealed a significant and moderate effect, while exer-score showed little impact, as did a game-only condition. Both exer-tour and exer-score conditions also resulted in significant improvements in verbal memory. Effects appear to generalize to self-reported everyday cognitive function. Pilot data, including salivary biomarkers and structural MRI, were gathered at baseline and 6 months; exercise dose was associated with increased BDNF as well as increased gray matter volume in the PFC and ACC. Improvement in memory was associated with an increase in the DLPFC. Improved executive function was associated with increased expression of exosomal miRNA-9. Interactive physical and cognitive exercise (both high and low mental challenge) yielded similarly significant cognitive benefit for adherent sMCI

The ADAS-Cog revisited: novel composite scales based on ADAS-Cog to improve efficiency in MCI and early AD trials.

Science.gov (United States)

Raghavan, Nandini; Samtani, Mahesh N; Farnum, Michael; Yang, Eric; Novak, Gerald; Grundman, Michael; Narayan, Vaibhav; DiBernardo, Allitia

2013-02-01

The Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog) has been used widely as a cognitive end point in Alzheimer's Disease (AD) clinical trials. Efforts to treat AD pathology at earlier stages have also used ADAS-Cog, but failure in these trials can be difficult to interpret because the scale has well-known ceiling effects that limit its use in mild cognitive impairment (MCI) and early AD. A wealth of data exists in ADAS-Cog from both historical trials and contemporary longitudinal natural history studies that can provide insights about parts of the scale that may be better suited for MCI and early AD trials. Using Alzheimer's Disease Neuroimaging Initiative study data, we identified the most informative cognitive measures from the ADAS-Cog and other available scales. We used cross-sectional analyses to characterize trajectories of ADAS-Cog and its individual subscales, as well as other cognitive, functional, or global measures across disease stages. Informative measures were identified based on standardized mean of 2-year change from baseline and were combined into novel composite endpoints. We assessed performance of the novel endpoints based on sample size requirements for a 2-year clinical trial. A bootstrap validation procedure was also undertaken to assess the reproducibility of the standardized mean changes of the selected measures and the corresponding composites. All proposed novel endpoints have improved standardized mean changes and thus improved statistical power compared with the ADAS-Cog 11. Further improvements were achieved by using cognitive-functional composites. Combining the novel composites with an enrichment strategy based on cerebral spinal fluid beta-amyloid (Aβ(1-42)) in a 2-year trial yielded gains in power of 20% to 40% over ADAS-Cog 11, regardless of the novel measure considered. An empirical, data-driven approach with existing instruments was used to derive novel composite scales based on ADAS-Cog 11 with improved performance

Fast damage imaging using the time-reversal technique in the frequency–wavenumber domain

International Nuclear Information System (INIS)

Zhu, R; Huang, G L; Yuan, F G

2013-01-01

The time-reversal technique has been successfully used in structural health monitoring (SHM) for quantitative imaging of damage. However, the technique is very time-consuming when it is implemented in the time domain. In this paper, we study the technique in the frequency–wavenumber (f–k) domain for fast real-time imaging of multiple damage sites in plates using scattered flexural plate waves. Based on Mindlin plate theory, the time reversibility of dispersive flexural waves in an isotropic plate is theoretically investigated in the f–k domain. A fast damage imaging technique is developed by using the cross-correlation between the back-propagated scattered wavefield and the incident wavefield in the frequency domain. Numerical simulations demonstrate that the proposed technique cannot only localize multiple damage sites but also potentially identify their sizes. Moreover, the time-reversal technique in the f–k domain is about two orders of magnitude faster than the method in the time domain. Finally, experimental testing of an on-line SHM system with a sparse piezoelectric sensor array is conducted for fast multiple damage identification using the proposed technique. (paper)

Domain Adversarial for Acoustic Emotion Recognition

OpenAIRE

Abdelwahab, Mohammed; Busso, Carlos

2018-01-01

The performance of speech emotion recognition is affected by the differences in data distributions between train (source domain) and test (target domain) sets used to build and evaluate the models. This is a common problem, as multiple studies have shown that the performance of emotional classifiers drop when they are exposed to data that does not match the distribution used to build the emotion classifiers. The difference in data distributions becomes very clear when the training and testing...

MULTIMODAL CLASSIFICATION OF DEMENTIA USING FUNCTIONAL DATA, ANATOMICAL FEATURES AND 3D INVARIANT SHAPE DESCRIPTORS.

Science.gov (United States)

Mikhno, Arthur; Nuevo, Pablo Martinez; Devanand, Davangere P; Parsey, Ramin V; Laine, Andrew F

2012-01-01

Multimodality classification of Alzheimer's disease (AD) and its prodromal stage, Mild Cognitive Impairment (MCI), is of interest to the medical community. We improve on prior classification frameworks by incorporating multiple features from MRI and PET data obtained with multiple radioligands, fluorodeoxyglucose (FDG) and Pittsburg compound B (PIB). We also introduce a new MRI feature, invariant shape descriptors based on 3D Zernike moments applied to the hippocampus region. Classification performance is evaluated on data from 17 healthy controls (CTR), 22 MCI, and 17 AD subjects. Zernike significantly outperforms volume, accuracy (Zernike to volume): CTR/AD (90.7% to 71.6%), CTR/MCI (76.2% to 60.0%), MCI/AD (84.3% to 65.5%). Zernike also provides comparable and complementary performance to PET. Optimal accuracy is achieved when Zernike and PET features are combined (accuracy, specificity, sensitivity), CTR/AD (98.8%, 99.5%, 98.1%), CTR/MCI (84.3%, 82.9%, 85.9%) and MCI/AD (93.3%, 93.6%, 93.3%).

Generation of human iPSC line GRX-MCiPS4F-A2 from adult peripheral blood mononuclear cells (PBMCs with Spanish genetic background

Directory of Open Access Journals (Sweden)

Sonia Cabrera

2015-09-01

Full Text Available We have generated iPSCs from peripheral blood mononuclear cells (PBMCs of a healthy man using heat sensitive and non-integrative Sendai virus containing Sox2, Oct3/4, c-Myc and Klf4. Human GRX-MCiPS4F-A2 cell line was established and characterized through this study.

Efficient Time-Domain Ray-Tracing Technique for the Analysis of Ultra-Wideband Indoor Environments including Lossy Materials and Multiple Effects

Directory of Open Access Journals (Sweden)

F. Saez de Adana

2009-01-01

Full Text Available This paper presents an efficient application of the Time-Domain Uniform Theory of Diffraction (TD-UTD for the analysis of Ultra-Wideband (UWB mobile communications for indoor environments. The classical TD-UTD formulation is modified to include the contribution of lossy materials and multiple-ray interactions with the environment. The electromagnetic analysis is combined with a ray-tracing acceleration technique to treat realistic and complex environments. The validity of this method is tested with measurements performed inside the Polytechnic building of the University of Alcala and shows good performance of the model for the analysis of UWB propagation.

Olfactory identification in amnestic and non-amnestic mild cognitive impairment and its neuropsychological correlates.

Science.gov (United States)

Vyhnalek, Martin; Magerova, Hana; Andel, Ross; Nikolai, Tomas; Kadlecova, Alexandra; Laczo, Jan; Hort, Jakub

2015-02-15

Olfactory identification impairment in amnestic mild cognitive impairment (aMCI) patients is well documented and considered to be caused by underlying Alzheimer's disease (AD) pathology, contrasting with less clear evidence in non-amnestic MCI (naMCI). The aim was to (a) compare the degree of olfactory identification dysfunction in aMCI, naMCI, controls and mild AD dementia and (b) assess the relation between olfactory identification and cognitive performance in aMCI compared to naMCI. 75 patients with aMCI and 32 with naMCI, 26 patients with mild AD and 27 controls underwent the multiple choice olfactory identification Motol Hospital Smell Test with 18 different odors together with a comprehensive neuropsychological examination. Controlling for age and gender, patients with aMCI and naMCI did not differ significantly in olfactory identification and both performed significantly worse than controls (pmemory and visuospatial tests were significantly related to better olfactory identification ability. Conversely, no cognitive measure was significantly related to olfactory performance in naMCI. Olfactory identification is similarly impaired in aMCI and naMCI. Olfactory impairment is proportional to cognitive impairment in aMCI but not in naMCI. Copyright © 2015. Published by Elsevier B.V.

A domain-based approach to predict protein-protein interactions

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Resat Haluk

2007-06-01

Full Text Available Abstract Background Knowing which proteins exist in a certain organism or cell type and how these proteins interact with each other are necessary for the understanding of biological processes at the whole cell level. The determination of the protein-protein interaction (PPI networks has been the subject of extensive research. Despite the development of reasonably successful methods, serious technical difficulties still exist. In this paper we present DomainGA, a quantitative computational approach that uses the information about the domain-domain interactions to predict the interactions between proteins. Results DomainGA is a multi-parameter optimization method in which the available PPI information is used to derive a quantitative scoring scheme for the domain-domain pairs. Obtained domain interaction scores are then used to predict whether a pair of proteins interacts. Using the yeast PPI data and a series of tests, we show the robustness and insensitivity of the DomainGA method to the selection of the parameter sets, score ranges, and detection rules. Our DomainGA method achieves very high explanation ratios for the positive and negative PPIs in yeast. Based on our cross-verification tests on human PPIs, comparison of the optimized scores with the structurally observed domain interactions obtained from the iPFAM database, and sensitivity and specificity analysis; we conclude that our DomainGA method shows great promise to be applicable across multiple organisms. Conclusion We envision the DomainGA as a first step of a multiple tier approach to constructing organism specific PPIs. As it is based on fundamental structural information, the DomainGA approach can be used to create potential PPIs and the accuracy of the constructed interaction template can be further improved using complementary methods. Explanation ratios obtained in the reported test case studies clearly show that the false prediction rates of the template networks constructed

SH3 Domains Differentially Stimulate Distinct Dynamin I Assembly Modes and G Domain Activity.

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Sai Krishnan

Full Text Available Dynamin I is a highly regulated GTPase enzyme enriched in nerve terminals which mediates vesicle fission during synaptic vesicle endocytosis. One regulatory mechanism involves its interactions with proteins containing Src homology 3 (SH3 domains. At least 30 SH3 domain-containing proteins bind dynamin at its proline-rich domain (PRD. Those that stimulate dynamin activity act by promoting its oligomerisation. We undertook a systematic parallel screening of 13 glutathione-S-transferase (GST-tagged endocytosis-related SH3 domains on dynamin binding, GTPase activity and oligomerisation. No correlation was found between dynamin binding and their potency to stimulate GTPase activity. There was limited correlation between the extent of their ability to stimulate dynamin activity and the level of oligomerisation, indicating an as yet uncharacterised allosteric coupling of the PRD and G domain. We examined the two variants, dynamin Iab and Ibb, which differ in the alternately splice middle domain α2 helix. They responded differently to the panel of SH3s, with the extent of stimulation between the splice variants varying greatly between the SH3s. This study reveals that SH3 binding can act as a heterotropic allosteric regulator of the G domain via the middle domain α2 helix, suggesting an involvement of this helix in communicating the PRD-mediated allostery. This indicates that SH3 binding both stabilises multiple conformations of the tetrameric building block of dynamin, and promotes assembly of dynamin-SH3 complexes with distinct rates of GTP hydrolysis.

AAA architectures applied in multi-domain IMS (IP Multimedia Subsystem)

NARCIS (Netherlands)

Ooms, W.S.; Karagiannis, G.; Deventer, M.O. van; Veldhuizen, J.

2007-01-01

There is a group of communication services that use resources from multiple domains in order to deliver their service. Authorization of the end-user is important for such services, because several domains are involved. There are no current solutions for delivering authentication, authorization and

AAA architectures applied in multi-domain IMS (IP multimedia subsystem)

NARCIS (Netherlands)

Ooms, W.S.; Karagiannis, Georgios; van Deventer, M.O.; Veldhuizen, J.; Devetsikiotis, M.; Michailidis, G.

2007-01-01

There is a group of communication services that use resources from multiple domains in order to deliver their service. Authorization of the end-user is important for such services, because several domains are involved. There are no current solutions for delivering authentication, authorization and

Mild cognitive impairment and deficits in instrumental activities of daily living: a systematic review.

Science.gov (United States)

Jekel, Katrin; Damian, Marinella; Wattmo, Carina; Hausner, Lucrezia; Bullock, Roger; Connelly, Peter J; Dubois, Bruno; Eriksdotter, Maria; Ewers, Michael; Graessel, Elmar; Kramberger, Milica G; Law, Emma; Mecocci, Patrizia; Molinuevo, José L; Nygård, Louise; Olde-Rikkert, Marcel Gm; Orgogozo, Jean-Marc; Pasquier, Florence; Peres, Karine; Salmon, Eric; Sikkes, Sietske Am; Sobow, Tomasz; Spiegel, René; Tsolaki, Magda; Winblad, Bengt; Frölich, Lutz

2015-01-01

There is a growing body of evidence that subtle deficits in instrumental activities of daily living (IADL) may be present in mild cognitive impairment (MCI). However, it is not clear if there are IADL domains that are consistently affected across patients with MCI. In this systematic review, therefore, we aimed to summarize research results regarding the performance of MCI patients in specific IADL (sub)domains compared with persons who are cognitively normal and/or patients with dementia. The databases PsycINFO, PubMed and Web of Science were searched for relevant literature in December 2013. Publications from 1999 onward were considered for inclusion. Altogether, 497 articles were retrieved. Reference lists of selected articles were searched for potentially relevant articles. After screening the abstracts of these 497 articles, 37 articles were included in this review. In 35 studies, IADL deficits (such as problems with medication intake, telephone use, keeping appointments, finding things at home and using everyday technology) were documented in patients with MCI. Financial capacity in patients with MCI was affected in the majority of studies. Effect sizes for group differences between patients with MCI and healthy controls were predominantly moderate to large. Performance-based instruments showed slight advantages (in terms of effect sizes) in detecting group differences in IADL functioning between patients with MCI, patients with Alzheimer's disease and healthy controls. IADL requiring higher neuropsychological functioning seem to be most severely affected in patients with MCI. A reliable identification of such deficits is necessary, as patients with MCI with IADL deficits seem to have a higher risk of converting to dementia than patients with MCI without IADL deficits. The use of assessment tools specifically designed and validated for patients with MCI is therefore strongly recommended. Furthermore, the development of performance-based assessment instruments

Spectral-domain low-coherence interferometry for phase-sensitive measurement of Faraday rotation at multiple depths.

Science.gov (United States)

Yeh, Yi-Jou; Black, Adam J; Akkin, Taner

2013-10-10

We describe a method for differential phase measurement of Faraday rotation from multiple depth locations simultaneously. A polarization-maintaining fiber-based spectral-domain interferometer that utilizes a low-coherent light source and a single camera is developed. Light decorrelated by the orthogonal channels of the fiber is launched on a sample as two oppositely polarized circular states. These states reflect from sample surfaces and interfere with the corresponding states of the reference arm. A custom spectrometer, which is designed to simplify camera alignment, separates the orthogonal channels and records the interference-related oscillations on both spectra. Inverse Fourier transform of the spectral oscillations in k-space yields complex depth profiles, whose amplitudes and phase difference are related to reflectivity and Faraday rotation within the sample, respectively. Information along a full depth profile is produced at the camera speed without performing an axial scan for a multisurface sample. System sensitivity for the Faraday rotation measurement is 0.86 min of arc. Verdet constants of clear liquids and turbid media are measured at 687 nm.

Intraindividual Variability across Neuropsychological Tests: Dispersion and Disengaged Lifestyle Increase Risk for Alzheimer’s Disease

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Drew W. R. Halliday

2018-03-01

Full Text Available Objective: Increased intraindividual variability (IIV in function has been linked to various age-related outcomes including cognitive decline and dementia. Most studies have operationalized IIV as fluctuations across trials (e.g., response latencies for a single task, with comparatively few studies examining variability across multiple tasks for a given individual. In the present study, we derive a multivariable operationalization of dispersion across a broad profile of neuropsychological measures and use this index along with degree of engaged lifestyle to predict risk of cognitive impairment. Participants and Methods: Participants (n = 60 were community-dwelling older adults aged 65+ years (M = 74.1, SD = 6.5 participating in a cross-sectional investigation of risk factors for amnestic mild cognitive impairment (a-MCI and probable Alzheimer’s Disease (AD. Participants were classified into three subgroups based on test performance and clinical judgement. Healthy controls (n = 30 scored better than −1 SD relative to existing norms on all classification measures, in the absence of memory complaints or functional impairments. The a-MCI group (n = 23 had self- or informant-reported memory complaints and scored 1 SD or more below the mean for at least one memory task while scoring better than 1 SD below the mean for all other cognitive domains, in the absence of functional impairments. The AD group (n = 7 scored at least 2 SD below the mean for two cognitive domains (including memory with impairments in functioning. Measures spanned a range of cognitive domains (episodic memory, executive function, language, with the derived dispersion estimates reflecting variability across an individual’s neuropsychological profile relative to the group average. Further, an Activities Lifestyle Questionnaire, indexing social, cognitive, and physical behaviors, was administered to assess the protective benefits of engaged lifestyle. Results: Multinomial

Characterizing brain patterns in conversion from mild cognitive impairment (MCI) to Alzheimer's disease

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Silva R., Santiago S.; Giraldo, Diana L.; Romero, Eduardo

2017-11-01

Structural Magnetic Resonance (MR) brain images should provide quantitative information about the stage and progression of Alzheimer's disease. However, the use of MRI is limited and practically reduced to corroborate a diagnosis already performed with neuropsychological tools. This paper presents an automated strategy for extraction of relevant anatomic patterns related with the conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) using T1-weighted MR images. The process starts by representing each of the possible classes with models generated from a linear combination of volumes. The difference between models allows us to establish which are the regions where relevant patterns might be located. The approach searches patterns in a space of brain sulci, herein approximated by the most representative gradients found in regions of interest defined by the difference between the linear models. This hypothesis is assessed by training a conventional SVM model with the found relevant patterns under a leave-one-out scheme. The resultant AUC was 0.86 for the group of women and 0.61 for the group of men.

Overview of multi-input frequency domain modal testing methods with an emphasis on sine testing

Science.gov (United States)

Rost, Robert W.; Brown, David L.

1988-01-01

An overview of the current state of the art multiple-input, multiple-output modal testing technology is discussed. A very brief review of the current time domain methods is given. A detailed review of frequency and spatial domain methods is presented with an emphasis on sine testing.

Comparisons of physical and chemical sputtering in high density divertor plasmas with the Monte Carlo Impurity (MCI) transport model

International Nuclear Information System (INIS)

Evans, T.E.; Loh, Y.S.; West, W.P.; Finkenthal, D.F.

1997-11-01

The MCI transport model was used to compare chemical and physical sputtering for a DIII-D divertor plasma near detachment. With physical sputtering alone the integrated carbon influx was 8.4 x 10 19 neutral/s while physical plus chemical sputtering produced an integrated carbon influx of 1.7 x 10 21 neutrals/s. The average carbon concentration in the computational volume increased from 0.012% with only physical sputtering to 0.182% with both chemical and physical sputtering. This increase in the carbon inventory produced more radiated power which is in better agreement with experimental measurements

Structure and dynamics of the human pleckstrin DEP domain: distinct molecular features of a novel DEP domain subfamily.

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Civera, Concepcion; Simon, Bernd; Stier, Gunter; Sattler, Michael; Macias, Maria J

2005-02-01

Pleckstrin1 is a major substrate for protein kinase C in platelets and leukocytes, and comprises a central DEP (disheveled, Egl-10, pleckstrin) domain, which is flanked by two PH (pleckstrin homology) domains. DEP domains display a unique alpha/beta fold and have been implicated in membrane binding utilizing different mechanisms. Using multiple sequence alignments and phylogenetic tree reconstructions, we find that 6 subfamilies of the DEP domain exist, of which pleckstrin represents a novel and distinct subfamily. To clarify structural determinants of the DEP fold and to gain further insight into the role of the DEP domain, we determined the three-dimensional structure of the pleckstrin DEP domain using heteronuclear NMR spectroscopy. Pleckstrin DEP shares main structural features with the DEP domains of disheveled and Epac, which belong to different DEP subfamilies. However, the pleckstrin DEP fold is distinct from these structures and contains an additional, short helix alpha4 inserted in the beta4-beta5 loop that exhibits increased backbone mobility as judged by NMR relaxation measurements. Based on sequence conservation, the helix alpha4 may also be present in the DEP domains of regulator of G-protein signaling (RGS) proteins, which are members of the same DEP subfamily. In pleckstrin, the DEP domain is surrounded by two PH domains. Structural analysis and charge complementarity suggest that the DEP domain may interact with the N-terminal PH domain in pleckstrin. Phosphorylation of the PH-DEP linker, which is required for pleckstrin function, could regulate such an intramolecular interaction. This suggests a role of the pleckstrin DEP domain in intramolecular domain interactions, which is distinct from the functions of other DEP domain subfamilies found so far.

[A follow-up study on a randomized, single-blind control of King's Brain pills in treatment of memory disorder in elderly people with MCI in a Beijing community].

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Tian, Jin-zhou; Zhu, Ai-hua; Zhong, Jian

2003-10-01

To evaluate the effect of King's Brain pills (Compound Chinese ginseng extract from herbs) on the treatment and the delaying of memory decline in the elderly with mild cognitive impairment (MCI) in a community by a year follow-up of neuropsychology. 75 patients with MCI were selected from Beixinqiao community of Beijing by a cutoff score of 0.0/0.5 on CDR and were randomly assigned into a treatment group (n = 30 cases), given 4 pills of a compound Chinese ginseng extract (King's Brain) with 2 placebo tablets, and a positive control group (n = 30 cases), given 2 tablets of Piracetam with 4 placebo tablets, as well as a placebo group (n = 15 cases), given a placebo of 4 tablets and 2 pills. All subjects took this medication 3 times a day for 3 months. Single-blind and double-moulding control were used in this study. At a baseline and a middlepoint (after 3 months), and a follow-up end (one year later) following a three months of medication therapeutics, all subjects were assessed using a battery consisting of MMSE and 5 memory items on BNPT battery. In the treatment group, MMSE score 27.50 +/- 1.68 was increased to 28.27 +/- 1.70 after 3 months but decreased to 26.90 +/- 1.90 after one year of the treatment. However, the latter score was higher than that in a placebo group 26.33 +/- 1.03 (P Brain spills and piracetam tablets have protective effect on cognitive and memory decline in elderly with MCI.

The DIMA web resource--exploring the protein domain network.

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Pagel, Philipp; Oesterheld, Matthias; Stümpflen, Volker; Frishman, Dmitrij

2006-04-15

Conserved domains represent essential building blocks of most known proteins. Owing to their role as modular components carrying out specific functions they form a network based both on functional relations and direct physical interactions. We have previously shown that domain interaction networks provide substantially novel information with respect to networks built on full-length protein chains. In this work we present a comprehensive web resource for exploring the Domain Interaction MAp (DIMA), interactively. The tool aims at integration of multiple data sources and prediction techniques, two of which have been implemented so far: domain phylogenetic profiling and experimentally demonstrated domain contacts from known three-dimensional structures. A powerful yet simple user interface enables the user to compute, visualize, navigate and download domain networks based on specific search criteria. http://mips.gsf.de/genre/proj/dima

Characterizing interdependencies of multiple time series theory and applications

CERN Document Server

Hosoya, Yuzo; Takimoto, Taro; Kinoshita, Ryo

2017-01-01

This book introduces academic researchers and professionals to the basic concepts and methods for characterizing interdependencies of multiple time series in the frequency domain. Detecting causal directions between a pair of time series and the extent of their effects, as well as testing the non existence of a feedback relation between them, have constituted major focal points in multiple time series analysis since Granger introduced the celebrated definition of causality in view of prediction improvement. Causality analysis has since been widely applied in many disciplines. Although most analyses are conducted from the perspective of the time domain, a frequency domain method introduced in this book sheds new light on another aspect that disentangles the interdependencies between multiple time series in terms of long-term or short-term effects, quantitatively characterizing them. The frequency domain method includes the Granger noncausality test as a special case. Chapters 2 and 3 of the book introduce an i...

Semistar-Krull and Valuative Dimension of Integral Domains

OpenAIRE

Sahandi, Parviz

2008-01-01

Given a stable semistar operation of finite type $\\star$ on an integral domain $D$, we show that it is possible to define in a canonical way a stable semistar operation of finite type $\\star[X]$ on the polynomial ring $D[X]$, such that, if $n:=\\star$-$\\dim(D)$, then $n+1\\leq \\star[X]\\text{-}\\dim(D[X])\\leq 2n+1$. We also establish that if $D$ is a $\\star$-Noetherian domain or is a Pr\\"{u}fer $\\star$-multiplication domain, then $\\star[X]\\text{-}\\dim(D[X])=\\star\\text{-}\\dim(D)+1$. Moreover we de...

Mild Cognitive Impairment Status and Mobility Performance

DEFF Research Database (Denmark)

Pedersen, Mette; Holt, Nicole E; Grande, Laura

2014-01-01

: An analysis was conducted on baseline data from the Boston Rehabilitative Impairment Study in the Elderly study, a cohort study of 430 primary care patients aged 65 or older. Neuropsychological tests identified participants with MCI and further subclassified those with impairment in memory domains (a......BACKGROUND: The prevalence of mild cognitive impairment (MCI) and mobility limitations is high among older adults. The aim of this study was to investigate the association between MCI status and both performance-based and self-report measures of mobility in community-dwelling older adults. METHODS...

The architectural design of networks of protein domain architectures.

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Hsu, Chia-Hsin; Chen, Chien-Kuo; Hwang, Ming-Jing

2013-08-23

Protein domain architectures (PDAs), in which single domains are linked to form multiple-domain proteins, are a major molecular form used by evolution for the diversification of protein functions. However, the design principles of PDAs remain largely uninvestigated. In this study, we constructed networks to connect domain architectures that had grown out from the same single domain for every single domain in the Pfam-A database and found that there are three main distinctive types of these networks, which suggests that evolution can exploit PDAs in three different ways. Further analysis showed that these three different types of PDA networks are each adopted by different types of protein domains, although many networks exhibit the characteristics of more than one of the three types. Our results shed light on nature's blueprint for protein architecture and provide a framework for understanding architectural design from a network perspective.

Transit Timing Observations from Kepler: III. Confirmation of 4 Multiple Planet Systems by a Fourier-Domain Study of Anti-correlated Transit Timing Variations

Energy Technology Data Exchange (ETDEWEB)

Steffen, Jason H.; /Fermilab; Fabrycky, Daniel C.; /Lick Observ.; Ford, Eric B.; /Florida U.; Carter, Joshua A.; /Harvard-Smithsonian Ctr. Astrophys.; Fressin, Francois; /Harvard-Smithsonian Ctr. Astrophys.; Holman, Matthew J.; /Harvard-Smithsonian Ctr. Astrophys.; Lissauer, Jack J.; /NASA, Ames; Rowe, Jason F.; /SETI Inst., Mtn. View /NASA, Ames; Ragozzine, Darin; /Harvard-Smithsonian Ctr. Astrophys.; Welsh, William F.; /Caltech; Borucki, William J.; /NASA, Ames /UC, Santa Barbara

2012-01-01

We present a method to confirm the planetary nature of objects in systems with multiple transiting exoplanet candidates. This method involves a Fourier-domain analysis of the deviations in the transit times from a constant period that result from dynamical interactions within the system. The combination of observed anticorrelations in the transit times and mass constraints from dynamical stability allow us to claim the discovery of four planetary systems, Kepler-25, Kepler-26, Kepler-27 and Kepler-28, containing eight planets and one additional planet candidate.

Salience Network and Depressive Severities in Parkinson's Disease with Mild Cognitive Impairment: A Structural Covariance Network Analysis.

Science.gov (United States)

Chang, Ya-Ting; Lu, Cheng-Hsien; Wu, Ming-Kung; Hsu, Shih-Wei; Huang, Chi-Wei; Chang, Wen-Neng; Lien, Chia-Yi; Lee, Jun-Jun; Chang, Chiung-Chih

2017-01-01

Purpose: In Parkinson's disease with mild cognitive impairment (PD-MCI), we investigated the clinical significance of salience network (SN) in depression and cognitive performance. Methods: Seventy seven PD-MCI patients that fulfilled multi-domain and non-amnestic subtype were included. Gray matter structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed based analysis. The patients were divided into two groups by psychiatric interviews and screening of Geriatric Depression Scale (GDS): PD-MCI with depression (PD-MCI-D) or without depression (PD-MCI-ND). The seed or peak cluster volume, or the significant differences in the regression slopes in each seed-peak cluster correlation, were used to evaluate the significance with the neurobehavioral scores. Results: This study is the first to demonstrate that the PD-MCI-ND group presented a larger number of voxels of structural covariance in SN than the PD-MCI-D group. The right fronto-insular seed volumes and the peak cluster of left lingual gyrus showed significant inverse correlation with the Geriatric Depression Scale (GDS; r = -0.231, P = 0.046). Conclusions: This study is the first to validate the clinical significance of the SN in PD-MCI-D. The right insular seed value and the SN correlated with the severity of depression in PD-MCI.

A comparison of non-homogeneous Markov regression models with application to Alzheimer’s disease progression

Science.gov (United States)

Hubbard, R. A.; Zhou, X.H.

2011-01-01

Markov regression models are useful tools for estimating the impact of risk factors on rates of transition between multiple disease states. Alzheimer’s disease (AD) is an example of a multi-state disease process in which great interest lies in identifying risk factors for transition. In this context, non-homogeneous models are required because transition rates change as subjects age. In this report we propose a non-homogeneous Markov regression model that allows for reversible and recurrent disease states, transitions among multiple states between observations, and unequally spaced observation times. We conducted simulation studies to demonstrate performance of estimators for covariate effects from this model and compare performance with alternative models when the underlying non-homogeneous process was correctly specified and under model misspecification. In simulation studies, we found that covariate effects were biased if non-homogeneity of the disease process was not accounted for. However, estimates from non-homogeneous models were robust to misspecification of the form of the non-homogeneity. We used our model to estimate risk factors for transition to mild cognitive impairment (MCI) and AD in a longitudinal study of subjects included in the National Alzheimer’s Coordinating Center’s Uniform Data Set. Using our model, we found that subjects with MCI affecting multiple cognitive domains were significantly less likely to revert to normal cognition. PMID:22419833

“En-Face” Spectral-Domain Optical Coherence Tomography Findings in Multiple Evanescent White Dot Syndrome

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Flore De bats

2014-01-01

Full Text Available Purpose. The recent use of “en-face” enhanced-depth imaging spectral-domain optical coherence tomography (EDI SD-OCT helps distinguish the retinal layers involved in the physiopathology of multiple evanescent white dot syndrome (MEWDS. Methods. Four patients presenting with MEWDS underwent a comprehensive ocular examination including C-scan (“en-face” EDI SD-OCT at the initial visit and during follow-up. Results. C-scans combined with the other multimodal imaging enabled the visualization of retinal damage. Acute lesions appeared as diffuse and focal disruptions occurring in the ellipsoid and interdigitation zones. The match between autofluorescence imaging, indocyanine green angiography, and “en-face” OCT helped identify the acute microstructural damages in the outer retina further than the choroid. Follow-up using “en-face” EDI-OCT revealed progressive and complete recovery of the central outer retinal layers. Conclusion. “En-face” EDI SD-OCT identified the site of initial damage in MEWDS as the photoreceptors and the interdigitation layers rather than the choroid. Moreover, “en-face” OCT is helpful in the follow-up of these lesions by being able to show the recovery of the outer retinal layers.

Expression and Production of SH2 Domain Proteins.

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Liu, Bernard A; Ogiue-Ikeda, Mari; Machida, Kazuya

2017-01-01

The Src Homology 2 (SH2) domain lies at the heart of phosphotyrosine signaling, coordinating signaling events downstream of receptor tyrosine kinases (RTKs), adaptors, and scaffolds. Over a hundred SH2 domains are present in mammals, each having a unique specificity which determines its interactions with multiple binding partners. One of the essential tools necessary for studying and determining the role of SH2 domains in phosphotyrosine signaling is a set of soluble recombinant SH2 proteins. Here we describe methods, based on a broad experience with purification of all SH2 domains, for the production of SH2 domain proteins needed for proteomic and biochemical-based studies such as peptide arrays, mass-spectrometry, protein microarrays, reverse-phase microarrays, and high-throughput fluorescence polarization (HTP-FP). We describe stepwise protocols for expression and purification of SH2 domains using GST or poly His-tags, two widely adopted affinity tags. In addition, we address alternative approaches, challenges, and validation studies for assessing protein quality and provide general characteristics of purified human SH2 domains.

Cooperative interactions between paired domain and homeodomain.

Science.gov (United States)

Jun, S; Desplan, C

1996-09-01

The Pax proteins are a family of transcriptional regulators involved in many developmental processes in all higher eukaryotes. They are characterized by the presence of a paired domain (PD), a bipartite DNA binding domain composed of two helix-turn-helix (HTH) motifs,the PAI and RED domains. The PD is also often associated with a homeodomain (HD) which is itself able to form homo- and hetero-dimers on DNA. Many of these proteins therefore contain three HTH motifs each able to recognize DNA. However, all PDs recognize highly related DNA sequences, and most HDs also recognize almost identical sites. We show here that different Pax proteins use multiple combinations of their HTHs to recognize several types of target sites. For instance, the Drosophila Paired protein can bind, in vitro, exclusively through its PAI domain, or through a dimer of its HD, or through cooperative interaction between PAI domain and HD. However, prd function in vivo requires the synergistic action of both the PAI domain and the HD. Pax proteins with only a PD appear to require both PAI and RED domains, while a Pax-6 isoform and a new Pax protein, Lune, may rely on the RED domain and HD. We propose a model by which Pax proteins recognize different target genes in vivo through various combinations of their DNA binding domains, thus expanding their recognition repertoire.

Orthogonal Multi-Carrier DS-CDMA with Frequency-Domain Equalization

Science.gov (United States)

Tanaka, Ken; Tomeba, Hiromichi; Adachi, Fumiyuki

Orthogonal multi-carrier direct sequence code division multiple access (orthogonal MC DS-CDMA) is a combination of orthogonal frequency division multiplexing (OFDM) and time-domain spreading, while multi-carrier code division multiple access (MC-CDMA) is a combination of OFDM and frequency-domain spreading. In MC-CDMA, a good bit error rate (BER) performance can be achieved by using frequency-domain equalization (FDE), since the frequency diversity gain is obtained. On the other hand, the conventional orthogonal MC DS-CDMA fails to achieve any frequency diversity gain. In this paper, we propose a new orthogonal MC DS-CDMA that can obtain the frequency diversity gain by applying FDE. The conditional BER analysis is presented. The theoretical average BER performance in a frequency-selective Rayleigh fading channel is evaluated by the Monte-Carlo numerical computation method using the derived conditional BER and is confirmed by computer simulation of the orthogonal MC DS-CDMA signal transmission.

Arbitrary and semantic associations in subjective memory impairment and amnestic mild cognitive impairment among Taiwanese individuals: A cross-sectional study

Directory of Open Access Journals (Sweden)

Hsin-Te Chang

2018-05-01

Full Text Available Background/Purpose: Researchers have recently proposed a preclinical stage of dementia of Alzheimer's type (DAT, referred to as subjective memory impairment (SMI, with the aim of developing methods for the early detection of DAT and subsequent intervention. It has been proposed that the objective memory functions of individuals with SMI are normal; however, arbitrary and semantic associations are both used to describe the processes of memory. No previous studies have investigated these processes among individuals with SMI. Methods: Cross-sectional analysis was used to compare the memory function of individuals with SMI, amnestic mild cognitive impairment (aMCI, or DAT. One hundred and eighty-three participants were recruited from the Memory Clinic of National Taiwan University Hospital and communities in northern Taiwan, including individuals with no memory complaints (HC, n = 30 and individuals with SMI (n = 61, aMCI-single domain (n = 24, aMCI-multiple domain (n = 33, or DAT (n = 35. The Word Sequence Learning Test (WSLT was used to assess the formation of arbitrary associations and the Logical Memory subtest of the Wechsler Memory Scale-Third Edition was used to assess the formation of semantic associations. Results: Compared to the HC group, the SMI group performed poorly only on the WSLT, whereas the other groups performed poorly on both of the memory tasks. This study demonstrated that SMI individuals tend to perform poorly in the formation of arbitrary associations. Conclusion: Our findings suggest that tasks requiring arbitrary associations may provide greater sensitivity in the detection cognitive changes associated with preclinical DAT. Keywords: Alzheimer's disease, Mild cognitive impairment, Neuropsychology, Dementia

Human alpha2-macroglobulin is composed of multiple domains, as predicted by homology with complement component C3.

Science.gov (United States)

Doan, Ninh; Gettins, Peter G W

2007-10-01

Human alpha2M (alpha2-macroglobulin) and the complement components C3 and C4 are thiol ester-containing proteins that evolved from the same ancestral gene. The recent structure determination of human C3 has allowed a detailed prediction of the location of domains within human alpha2M to be made. We describe here the expression and characterization of three alpha(2)M domains predicted to be involved in the stabilization of the thiol ester in native alpha2M and in its activation upon bait region proteolysis. The three newly expressed domains are MG2 (macroglobulin domain 2), TED (thiol ester-containing domain) and CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain. Together with the previously characterized RBD (receptor-binding domain), they represent approx. 42% of the alpha2M polypeptide. Their expression as folded domains strongly supports the predicted domain organization of alpha2M. An X-ray crystal structure of MG2 shows it to have a fibronectin type-3 fold analogous to MG1-MG8 of C3. TED is, as predicted, an alpha-helical domain. CUB is a spliced domain composed of two stretches of polypeptide that flank TED in the primary structure. In intact C3 TED interacts with RBD, where it is in direct contact with the thiol ester, and with MG2 and CUB on opposite, flanking sides. In contrast, these alpha2M domains, as isolated species, show negligible interaction with one another, suggesting that the native conformation of alpha2M, and the consequent thiol ester-stabilizing domain-domain interactions, result from additional restraints imposed by the physical linkage of these domains or by additional domains in the protein.

The Vallecas Project: a cohort to identify early markers and mechanisms of Alzheimer's disease

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Javier eOlazarán

2015-09-01

Full Text Available Introduction. Alzheimer’s disease (AD is a major threat for the well-being of an increasingly aged world population. The physiopathological mechanisms of late-onset AD are multiple, possibly heterogeneous, and not well understood. Different combinations of variables from several domains (i.e., clinical, neuropsychological, structural, and biochemical markers may predict dementia conversion, according to distinct physiopathological pathways, in different groups of subjects. Methods. We launched the Vallecas Project (VP, a cohort study of non-demented people aged 70 to 85, to characterize the social, clinical, neuropsychological, structural, and biochemical underpinnings of AD inception. Given the exploratory nature of the VP, multidimensional and machine learning techniques will be applied, in addition to the traditional multivariate statistical methods. Results. A total of 1,169 subjects were recruited between October 2011 and December 2013. Mean age was 74.4 years (SD 3.9, 63.5% of the subjects were women, and 17.9% of the subjects were carriers of at least one ε4 allele of the apolipoprotein E (APOE gene. Cognitive diagnoses at inclusion were as follows: normal cognition 93.0% and mild cognitive impairment (MCI 7.0% (3.1% amnestic MCI, 0.1% non-amnestic MCI, 3.8% mixed MCI. Blood samples were obtained and stored for future determinations in 99.9% of the subjects and 3T magnetic resonance imaging (MRI study was conducted in 89.9% of the volunteers. The cohort is being followed up annually for four years after the baseline. Conclusion. We have established a valuable homogeneous single-center cohort which, by identifying groups of variables associated with high risk of MCI or dementia conversion, should help to clarify the early physiopathological mechanisms of AD and should provide avenues for prompt diagnosis and AD prevention.

Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone

Energy Technology Data Exchange (ETDEWEB)

Paz-Filho, G.J.; Mesa-Junior, C.O.; Boguszewski, C.L.; Carvalho, G.A.; Graf, H. [Universidade Federal do Parana (UFPR), Curitiba, PR (Brazil). Hospital de Clinicas. Servico de Endocrinologia e Metabologia; Olandoski, M. [Pontificia Univ. Catolica do Parana, Curitiba, PR (Brazil). Nucleo de Bioestatistica; Woellner, L.C. [Centro de Medicina Nuclear, Curitiba, PR (Brazil); Goedert, C.A. [Centro de Tomografia Computadorizada, Curitiba, PR (Brazil)

2007-12-15

Recombinant human thyroid-stimulating hormone (rhTSH) enhances {sup 131}I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG). Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi {sup 131}I, in patients with MNG. Seventeen patients (15 females, 59.0 {+-} 13.1 years), who had never been submitted to {sup 131}I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi {sup 131}I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 {+-} 64.4 mL. {sup 131}I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean {sup 131}I 24-h uptake increased from 18.1 {+-} 9.7 to 49.6 {+-} 13.4% (P < 0.001), a median 2.6-fold increase (1.2 to 9.2). Peak hormonal levels were 10.86 {+-} 5.44 mU/L for TSH (a median 15.5-fold increase), 1.80 {+-} 0.48 ng/dL for free-T4, 204.61 {+-} 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6%), painful thyroiditis (29.4%) and hypothyroidism (52.9%). Thyroid volume was reduced by 34.3 {+-} 14.3% after 6 months (P < 0.001) and by 46.0 {+-} 14.6% after 1 year (P < 0.001). Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of {sup 131}I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects. (author)

Effect of 30 mCi radioiodine on multinodular goiter previously treated with recombinant human thyroid-stimulating hormone

Directory of Open Access Journals (Sweden)

G.J. Paz-Filho

2007-12-01

Full Text Available Recombinant human thyroid-stimulating hormone (rhTSH enhances 131I uptake, permitting a decrease in radiation for the treatment of multinodular goiter (MNG. Our objective was to evaluate the safety and efficacy of a single 0.1-mg dose of rhTSH, followed by 30 mCi 131I, in patients with MNG. Seventeen patients (15 females, 59.0 ± 13.1 years, who had never been submitted to 131I therapy, received a single 0.1-mg injection of rhTSH followed by 30 mCi 131I on the next day. Mean basal thyroid volume measured by computed tomography was 106.1 ± 64.4 mL. 131I 24-h uptake, TSH, free-T4, T3, thyroglobulin, anti-thyroid antibodies, and thyroid volume were evaluated at regular intervals of 12 months. Mean 131I 24-h uptake increased from 18.1 ± 9.7 to 49.6 ± 13.4% (P < 0.001, a median 2.6-fold increase (1.2 to 9.2. Peak hormonal levels were 10.86 ± 5.44 mU/L for TSH (a median 15.5-fold increase, 1.80 ± 0.48 ng/dL for free-T4, 204.61 ± 58.37 ng/dL for T3, and a median of 557.0 ng/mL for thyroglobulin. The adverse effects observed were hyperthyroidism (17.6%, painful thyroiditis (29.4% and hypothyroidism (52.9%. Thyroid volume was reduced by 34.3 ± 14.3% after 6 months (P < 0.001 and by 46.0 ± 14.6% after 1 year (P < 0.001. Treatment of MNG with a single 0.1-mg dose of rhTSH, followed by a fixed amount of radioactivity of 131I, leads to an efficacious decrease in thyroid volume for the majority of the patients, with a moderate incidence of non-serious and readily treatable adverse effects.

Mild cognitive impairment (MCI) - the novel trend of targeting Alzheimer's disease in its early stages - methodological considerations.

Science.gov (United States)

Pater, C

2011-11-01

While much uncertainty exists in the estimates of the global burden of Alzheimer's disease and about the potential impact of various interventions, there is a widespread acceptance of the fact that the steady increase in the incidence and prevalence of the condition worldwide is becoming a massive public health problem as well as a huge economic burden for all healthcare systems and societies. These heavy demands are further compounded by the poor quality of life of the affected individuals, of their families and of their caregivers. The epidemic proportion of Alzheimer's disease has triggered relentless attempts for development of treatment approaches during the past two decades by a multitude of pharmaceuticals and biotech companies. Commercial development of the acetylcholinesterase inhibitors has, until recently, virtually dominated the field and, although efficacy has been demonstrated for five different products, the longterm clinical results suggested that alternate approaches were warranted. Disease modifying strategies targeting the β- amyloid plaques (e.g., decreasing β-amyloid formation through β- and γ-secretase inhibition, diminishing β-amyloid aggregation through anti-aggregants or enhancement of β-amyloid clearance through active/passive immunization), targeting the neurofibrillary tangles through inhibition of tau protein hyperphosphorilation or, more recently, by increasing mitochondrial permeability, all these potential treatment modalities are facing major methodological challenges during the conduct of a myriad of clinical trials meant to bring the novel therapies to the market. Failure of more than 400 products tested in more than 800 clinical trials to date, with many of these failures occurring in late stage development (phase III) have triggered a paradigm shift toward targeting of the early stages of cognitive deficiencies (mild cognitive impairment- MCI) and a refinement of the investigative methodologies. The great heterogeneity of

Human α2-macroglobulin is composed of multiple domains, as predicted by homology with complement component C3

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Doan, Ninh; Gettins, Peter G. W.

2007-01-01

Human α2M (α2-macroglobulin) and the complement components C3 and C4 are thiol ester-containing proteins that evolved from the same ancestral gene. The recent structure determination of human C3 has allowed a detailed prediction of the location of domains within human α2M to be made. We describe here the expression and characterization of three α2M domains predicted to be involved in the stabilization of the thiol ester in native α2M and in its activation upon bait region proteolysis. The three newly expressed domains are MG2 (macroglobulin domain 2), TED (thiol ester-containing domain) and CUB (complement protein subcomponents C1r/C1s, urchin embryonic growth factor and bone morphogenetic protein 1) domain. Together with the previously characterized RBD (receptor-binding domain), they represent approx. 42% of the α2M polypeptide. Their expression as folded domains strongly supports the predicted domain organization of α2M. An X-ray crystal structure of MG2 shows it to have a fibronectin type-3 fold analogous to MG1–MG8 of C3. TED is, as predicted, an α-helical domain. CUB is a spliced domain composed of two stretches of polypeptide that flank TED in the primary structure. In intact C3 TED interacts with RBD, where it is in direct contact with the thiol ester, and with MG2 and CUB on opposite, flanking sides. In contrast, these α2M domains, as isolated species, show negligible interaction with one another, suggesting that the native conformation of α2M, and the consequent thiol ester-stabilizing domain–domain interactions, result from additional restraints imposed by the physical linkage of these domains or by additional domains in the protein. PMID:17608619

Protein domain organisation: adding order.

Science.gov (United States)

Kummerfeld, Sarah K; Teichmann, Sarah A

2009-01-29

Domains are the building blocks of proteins. During evolution, they have been duplicated, fused and recombined, to produce proteins with novel structures and functions. Structural and genome-scale studies have shown that pairs or groups of domains observed together in a protein are almost always found in only one N to C terminal order and are the result of a single recombination event that has been propagated by duplication of the multi-domain unit. Previous studies of domain organisation have used graph theory to represent the co-occurrence of domains within proteins. We build on this approach by adding directionality to the graphs and connecting nodes based on their relative order in the protein. Most of the time, the linear order of domains is conserved. However, using the directed graph representation we have identified non-linear features of domain organization that are over-represented in genomes. Recognising these patterns and unravelling how they have arisen may allow us to understand the functional relationships between domains and understand how the protein repertoire has evolved. We identify groups of domains that are not linearly conserved, but instead have been shuffled during evolution so that they occur in multiple different orders. We consider 192 genomes across all three kingdoms of life and use domain and protein annotation to understand their functional significance. To identify these features and assess their statistical significance, we represent the linear order of domains in proteins as a directed graph and apply graph theoretical methods. We describe two higher-order patterns of domain organisation: clusters and bi-directionally associated domain pairs and explore their functional importance and phylogenetic conservation. Taking into account the order of domains, we have derived a novel picture of global protein organization. We found that all genomes have a higher than expected degree of clustering and more domain pairs in forward and

Protein domain organisation: adding order

Directory of Open Access Journals (Sweden)

Kummerfeld Sarah K

2009-01-01

Full Text Available Abstract Background Domains are the building blocks of proteins. During evolution, they have been duplicated, fused and recombined, to produce proteins with novel structures and functions. Structural and genome-scale studies have shown that pairs or groups of domains observed together in a protein are almost always found in only one N to C terminal order and are the result of a single recombination event that has been propagated by duplication of the multi-domain unit. Previous studies of domain organisation have used graph theory to represent the co-occurrence of domains within proteins. We build on this approach by adding directionality to the graphs and connecting nodes based on their relative order in the protein. Most of the time, the linear order of domains is conserved. However, using the directed graph representation we have identified non-linear features of domain organization that are over-represented in genomes. Recognising these patterns and unravelling how they have arisen may allow us to understand the functional relationships between domains and understand how the protein repertoire has evolved. Results We identify groups of domains that are not linearly conserved, but instead have been shuffled during evolution so that they occur in multiple different orders. We consider 192 genomes across all three kingdoms of life and use domain and protein annotation to understand their functional significance. To identify these features and assess their statistical significance, we represent the linear order of domains in proteins as a directed graph and apply graph theoretical methods. We describe two higher-order patterns of domain organisation: clusters and bi-directionally associated domain pairs and explore their functional importance and phylogenetic conservation. Conclusion Taking into account the order of domains, we have derived a novel picture of global protein organization. We found that all genomes have a higher than expected

Clinical relevance of specific cognitive complaints in determining Mild Cognitive Impairment from Cognitively Normal States in a study of Healthy Elderly Controls

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Marina Avila Villanueva

2016-10-01

Full Text Available Introduction: Subjective memory complaints in the elderly have been suggested as an early sign of dementia. This study aims at investigating whether specific cognitive complaints are more useful than others to discriminate Mild Cognitive Impairment (MCI by examining the dimensional structure of the Everyday Memory Questionnaire (EMQ.Material and Methods: A sample of community-dwelling elderly individuals was recruited (766 controls and 78 MCI. The Everyday Memory Questionnaire (EMQ was administered to measure self-perception of cognitive complaints. All participants also underwent a comprehensive clinical and neuropsychological battery. Combined exploratory factor analysis and item response theory were performed to identify the underlying structure of the EMQ. Furthermore, logistic regression analyses were conducted to study whether single cognitive complaints were able to predict MCI.Results: A suitable five-factor solution was found. Each factor focused on a different cognitive domain. Interestingly, just three of them, namely forgetfulness of immediate information, executive functions and prospective memory proved to be effective in distinguishing between cognitively healthy individuals and MCI. Based on these results we propose a shortened EMQ version comprising 10 items (EMQ-10.Discussion: Not all cognitive complaints have the same clinical relevance. Only subjective complaints on specific cognitive domains are able to discriminate MCI. We encourage clinicians to the EMQ-10 as a useful tool to quantify and monitor the progression of individuals who report cognitive complaints.

Answer selection in a multi-stream open domain question answering system

NARCIS (Netherlands)

Jijkoun, V.; de Rijke, M.; McDonald, S.; Tait, J.

2004-01-01

Question answering systems aim to meet users' information needs by returning exact answers in response to a question. Traditional open domain question answering systems are built around a single pipeline architecture. In an attempt to exploit multiple resources as well as multiple answering

Extent and neural basis of semantic memory impairment in mild cognitive impairment.

Science.gov (United States)

Barbeau, Emmanuel J; Didic, Mira; Joubert, Sven; Guedj, Eric; Koric, Lejla; Felician, Olivier; Ranjeva, Jean-Philippe; Cozzone, Patrick; Ceccaldi, Mathieu

2012-01-01

An increasing number of studies indicate that semantic memory is impaired in mild cognitive impairment (MCI). However, the extent and the neural basis of this impairment remain unknown. The aim of the present study was: 1) to evaluate whether all or only a subset of semantic domains are impaired in MCI patients; and 2) to assess the neural substrate of the semantic impairment in MCI patients using voxel-based analysis of MR grey matter density and SPECT perfusion. 29 predominantly amnestic MCI patients and 29 matched control subjects participated in this study. All subjects underwent a full neuropsychological assessment, along with a battery of five tests evaluating different domains of semantic memory. A semantic memory composite Z-score was established on the basis of this battery and was correlated with MRI grey matter density and SPECT perfusion measures. MCI patients were found to have significantly impaired performance across all semantic tasks, in addition to their anterograde memory deficit. Moreover, no temporal gradient was found for famous faces or famous public events and knowledge for the most remote decades was also impaired. Neuroimaging analyses revealed correlations between semantic knowledge and perirhinal/entorhinal areas as well as the anterior hippocampus. Therefore, the deficits in the realm of semantic memory in patients with MCI is more widespread than previously thought and related to dysfunction of brain areas beyond the limbic-diencephalic system involved in episodic memory. The severity of the semantic impairment may indicate a decline of semantic memory that began many years before the patients first consulted.

Natural-Annotation-based Unsupervised Construction of Korean-Chinese Domain Dictionary

Science.gov (United States)

Liu, Wuying; Wang, Lin

2018-03-01

The large-scale bilingual parallel resource is significant to statistical learning and deep learning in natural language processing. This paper addresses the automatic construction issue of the Korean-Chinese domain dictionary, and presents a novel unsupervised construction method based on the natural annotation in the raw corpus. We firstly extract all Korean-Chinese word pairs from Korean texts according to natural annotations, secondly transform the traditional Chinese characters into the simplified ones, and finally distill out a bilingual domain dictionary after retrieving the simplified Chinese words in an extra Chinese domain dictionary. The experimental results show that our method can automatically build multiple Korean-Chinese domain dictionaries efficiently.

Magnetization reversal in ferromagnetic spirals via domain wall motion

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Schumm, Ryan D.; Kunz, Andrew

2016-11-01

Domain wall dynamics have been investigated in a variety of ferromagnetic nanostructures for potential applications in logic, sensing, and recording. We present a combination of analytic and simulated results describing the reliable field driven motion of a domain wall through the arms of a ferromagnetic spiral nanowire. The spiral geometry is capable of taking advantage of the benefits of both straight and circular wires. Measurements of the in-plane components of the spirals' magnetization can be used to determine the angular location of the domain wall, impacting the magnetoresistive applications dependent on the domain wall location. The spirals' magnetization components are found to depend on the spiral parameters: the initial radius and spacing between spiral arms, along with the domain wall location. The magnetization is independent of the parameters of the rotating field used to move the domain wall, and therefore the model is valid for current induced domain wall motion as well. The speed of the domain wall is found to depend on the frequency of the rotating driving field, and the domain wall speeds can be reliably varied over several orders of magnitude. We further demonstrate a technique capable of injecting multiple domain walls and show the reliable and unidirectional motion of domain walls through the arms of the spiral.

Mild cognitive impairment: applicability of research criteria in a memory clinic and characterization of cognitive profile.

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Alladi, Suvarna; Arnold, Robert; Mitchell, Joanna; Nestor, Peter J; Hodges, John R

2006-04-01

We explored the applicability of recently proposed research criteria for mild cognitive impairment (MCI) in a memory clinic and changes in case definition related to which memory tests are used and the status of general cognitive function in MCI. A total of 166 consecutive GP referrals to the Cambridge Memory Clinic underwent comprehensive neuropsychological and psychiatric evaluation. Of 166 cases, 42 were excluded (significant depression 8, established dementia 29 and other disorders 5). Of 124 non-demented, non-depressed patients, 72 fulfilled Petersen's criteria for amnestic MCI based upon verbal memory performance [the Rey Auditory Verbal Learning Test (RAVLT)] and 90 met criteria if performance on verbal and/or non-verbal memory tests [the Rey figure recall or the Paired Associates Learning test (PAL)] was considered. Of the 90 broadly defined MCI cases, only 25 had pure amnesia: other subtle semantic and/or attention deficits were typically present. A further 12 were classed as non-amnestic MCI and 22 as 'worried well'. Definition of MCI varies considerably dependent upon the tests used for case definition. The majority have other cognitive deficits despite normal performance on the Mini-mental State Examination (MMSE) and intact activities of daily living (ADL) and fit within multi-domain MCI. Pure amnesic MCI is rare.

Multiple Taf subunits of TFIID interact with Ino2 activation domains and contribute to expression of genes required for yeast phospholipid biosynthesis.

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Hintze, Stefan; Engelhardt, Maike; van Diepen, Laura; Witt, Eric; Schüller, Hans-Joachim

2017-12-01

Expression of phospholipid biosynthetic genes in yeast requires activator protein Ino2 which can bind to the UAS element inositol/choline-responsive element (ICRE) and trigger activation of target genes, using two separate transcriptional activation domains, TAD1 and TAD2. However, it is still unknown which cofactors mediate activation by TADs of Ino2. Here, we show that multiple subunits of basal transcription factor TFIID (TBP-associated factors Taf1, Taf4, Taf6, Taf10 and Taf12) are able to interact in vitro with activation domains of Ino2. Interaction was no longer observed with activation-defective variants of TAD1. We were able to identify two nonoverlapping regions in the N-terminus of Taf1 (aa 1-100 and aa 182-250) each of which could interact with TAD1 of Ino2 as well as with TAD4 of activator Adr1. Specific missense mutations within Taf1 domain aa 182-250 affecting basic and hydrophobic residues prevented interaction with wild-type TAD1 and caused reduced expression of INO1. Using chromatin immunoprecipitation we demonstrated Ino2-dependent recruitment of Taf1 and Taf6 to ICRE-containing promoters INO1 and CHO2. Transcriptional derepression of INO1 was no longer possible with temperature-sensitive taf1 and taf6 mutants cultivated under nonpermissive conditions. This result supports the hypothesis of Taf-dependent expression of structural genes activated by Ino2. © 2017 John Wiley & Sons Ltd.

Salience Network and Depressive Severities in Parkinson’s Disease with Mild Cognitive Impairment: A Structural Covariance Network Analysis

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Ya-Ting Chang

2018-01-01

Full Text Available Purpose: In Parkinson’s disease with mild cognitive impairment (PD-MCI, we investigated the clinical significance of salience network (SN in depression and cognitive performance.Methods: Seventy seven PD-MCI patients that fulfilled multi-domain and non-amnestic subtype were included. Gray matter structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed based analysis. The patients were divided into two groups by psychiatric interviews and screening of Geriatric Depression Scale (GDS: PD-MCI with depression (PD-MCI-D or without depression (PD-MCI-ND. The seed or peak cluster volume, or the significant differences in the regression slopes in each seed-peak cluster correlation, were used to evaluate the significance with the neurobehavioral scores.Results: This study is the first to demonstrate that the PD-MCI-ND group presented a larger number of voxels of structural covariance in SN than the PD-MCI-D group. The right fronto-insular seed volumes and the peak cluster of left lingual gyrus showed significant inverse correlation with the Geriatric Depression Scale (GDS; r = -0.231, P = 0.046.Conclusions: This study is the first to validate the clinical significance of the SN in PD-MCI-D. The right insular seed value and the SN correlated with the severity of depression in PD-MCI.

Salience Network and Depressive Severities in Parkinson’s Disease with Mild Cognitive Impairment: A Structural Covariance Network Analysis

Science.gov (United States)

Chang, Ya-Ting; Lu, Cheng-Hsien; Wu, Ming-Kung; Hsu, Shih-Wei; Huang, Chi-Wei; Chang, Wen-Neng; Lien, Chia-Yi; Lee, Jun-Jun; Chang, Chiung-Chih

2018-01-01

Purpose: In Parkinson’s disease with mild cognitive impairment (PD-MCI), we investigated the clinical significance of salience network (SN) in depression and cognitive performance. Methods: Seventy seven PD-MCI patients that fulfilled multi-domain and non-amnestic subtype were included. Gray matter structural covariance networks were constructed by 3D T1-magnetic resonance imaging and seed based analysis. The patients were divided into two groups by psychiatric interviews and screening of Geriatric Depression Scale (GDS): PD-MCI with depression (PD-MCI-D) or without depression (PD-MCI-ND). The seed or peak cluster volume, or the significant differences in the regression slopes in each seed-peak cluster correlation, were used to evaluate the significance with the neurobehavioral scores. Results: This study is the first to demonstrate that the PD-MCI-ND group presented a larger number of voxels of structural covariance in SN than the PD-MCI-D group. The right fronto-insular seed volumes and the peak cluster of left lingual gyrus showed significant inverse correlation with the Geriatric Depression Scale (GDS; r = -0.231, P = 0.046). Conclusions: This study is the first to validate the clinical significance of the SN in PD-MCI-D. The right insular seed value and the SN correlated with the severity of depression in PD-MCI. PMID:29375361

Why Johnny Struggles When Familiar Concepts Are Taken to a New Mathematical Domain: Towards a Polysemous Approach

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Kontorovich, Igor'

2018-01-01

This article is concerned with cognitive aspects of students' struggles in situations in which familiar concepts are reconsidered in a new mathematical domain. Examples of such cross-curricular concepts are divisibility in the domain of integers and in the domain of polynomials, multiplication in the domain of numbers and in the domain of vectors,…

NovelFam3000 – Uncharacterized human protein domains conserved across model organisms

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Kemmer, Danielle; Podowski, Raf M; Arenillas, David; Lim, Jonathan; Hodges, Emily; Roth, Peggy; Sonnhammer, Erik LL; Höög, Christer; Wasserman, Wyeth W

2006-01-01

Background Despite significant efforts from the research community, an extensive portion of the proteins encoded by human genes lack an assigned cellular function. Most metazoan proteins are composed of structural and/or functional domains, of which many appear in multiple proteins. Once a domain is characterized in one protein, the presence of a similar sequence in an uncharacterized protein serves as a basis for inference of function. Thus knowledge of a domain's function, or the protein within which it arises, can facilitate the analysis of an entire set of proteins. Description From the Pfam domain database, we extracted uncharacterized protein domains represented in proteins from humans, worms, and flies. A data centre was created to facilitate the analysis of the uncharacterized domain-containing proteins. The centre both provides researchers with links to dispersed internet resources containing gene-specific experimental data and enables them to post relevant experimental results or comments. For each human gene in the system, a characterization score is posted, allowing users to track the progress of characterization over time or to identify for study uncharacterized domains in well-characterized genes. As a test of the system, a subset of 39 domains was selected for analysis and the experimental results posted to the NovelFam3000 system. For 25 human protein members of these 39 domain families, detailed sub-cellular localizations were determined. Specific observations are presented based on the analysis of the integrated information provided through the online NovelFam3000 system. Conclusion Consistent experimental results between multiple members of a domain family allow for inferences of the domain's functional role. We unite bioinformatics resources and experimental data in order to accelerate the functional characterization of scarcely annotated domain families. PMID:16533400

NovelFam3000 – Uncharacterized human protein domains conserved across model organisms

Directory of Open Access Journals (Sweden)

Sonnhammer Erik LL

2006-03-01

Full Text Available Abstract Background Despite significant efforts from the research community, an extensive portion of the proteins encoded by human genes lack an assigned cellular function. Most metazoan proteins are composed of structural and/or functional domains, of which many appear in multiple proteins. Once a domain is characterized in one protein, the presence of a similar sequence in an uncharacterized protein serves as a basis for inference of function. Thus knowledge of a domain's function, or the protein within which it arises, can facilitate the analysis of an entire set of proteins. Description From the Pfam domain database, we extracted uncharacterized protein domains represented in proteins from humans, worms, and flies. A data centre was created to facilitate the analysis of the uncharacterized domain-containing proteins. The centre both provides researchers with links to dispersed internet resources containing gene-specific experimental data and enables them to post relevant experimental results or comments. For each human gene in the system, a characterization score is posted, allowing users to track the progress of characterization over time or to identify for study uncharacterized domains in well-characterized genes. As a test of the system, a subset of 39 domains was selected for analysis and the experimental results posted to the NovelFam3000 system. For 25 human protein members of these 39 domain families, detailed sub-cellular localizations were determined. Specific observations are presented based on the analysis of the integrated information provided through the online NovelFam3000 system. Conclusion Consistent experimental results between multiple members of a domain family allow for inferences of the domain's functional role. We unite bioinformatics resources and experimental data in order to accelerate the functional characterization of scarcely annotated domain families.

The Hardy Space of a Slit Domain

CERN Document Server

Aleman, Alexandru

2009-01-01

Beginning with an exposition of Hardy spaces of slit domains, this book proceeds to several descriptions of the invariant subspaces of the operator multiplication by z. It also discusses and characterizes the nearly invariant subspaces of these Hardy spaces and examines conditions for z-invariant subspaces to be cyclic.

A two-dimensional time domain near zone to far zone transformation

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Luebbers, Raymond J.; Ryan, Deirdre; Beggs, John H.; Kunz, Karl S.

1991-01-01

In a previous paper, a time domain transformation useful for extrapolating 3-D near zone finite difference time domain (FDTD) results to the far zone was presented. In this paper, the corresponding 2-D transform is outlined. While the 3-D transformation produced a physically observable far zone time domain field, this is not convenient to do directly in 2-D, since a convolution would be required. However, a representative 2-D far zone time domain result can be obtained directly. This result can then be transformed to the frequency domain using a Fast Fourier Transform, corrected with a simple multiplicative factor, and used, for example, to calculate the complex wideband scattering width of a target. If an actual time domain far zone result is required it can be obtained by inverse Fourier transform of the final frequency domain result.

Student Assessment System. Domain Referenced Tests. Transportation/Automotive Mechanics. Volume II: Theory. Georgia Vocational Education Program Articulation.

Science.gov (United States)

Watkins, James F., Comp.

These written domain referenced tests (DRTs) for the area of transportation/automotive mechanics test cognitive abilities or knowledge of theory. Introductory materials describe domain referenced testing and test development. Each multiple choice test includes a domain statement, describing the behavior and content of the domain, and a test item…

Identification of multiple binding sites for the THAP domain of the Galileo transposase in the long terminal inverted-repeats☆

Science.gov (United States)

Marzo, Mar; Liu, Danxu; Ruiz, Alfredo; Chalmers, Ronald

2013-01-01

Galileo is a DNA transposon responsible for the generation of several chromosomal inversions in Drosophila. In contrast to other members of the P-element superfamily, it has unusually long terminal inverted-repeats (TIRs) that resemble those of Foldback elements. To investigate the function of the long TIRs we derived consensus and ancestral sequences for the Galileo transposase in three species of Drosophilids. Following gene synthesis, we expressed and purified their constituent THAP domains and tested their binding activity towards the respective Galileo TIRs. DNase I footprinting located the most proximal DNA binding site about 70 bp from the transposon end. Using this sequence we identified further binding sites in the tandem repeats that are found within the long TIRs. This suggests that the synaptic complex between Galileo ends may be a complicated structure containing higher-order multimers of the transposase. We also attempted to reconstitute Galileo transposition in Drosophila embryos but no events were detected. Thus, although the limited numbers of Galileo copies in each genome were sufficient to provide functional consensus sequences for the THAP domains, they do not specify a fully active transposase. Since the THAP recognition sequence is short, and will occur many times in a large genome, it seems likely that the multiple binding sites within the long, internally repetitive, TIRs of Galileo and other Foldback-like elements may provide the transposase with its binding specificity. PMID:23648487

Identification of multiple binding sites for the THAP domain of the Galileo transposase in the long terminal inverted-repeats.

Science.gov (United States)

Marzo, Mar; Liu, Danxu; Ruiz, Alfredo; Chalmers, Ronald

2013-08-01

Galileo is a DNA transposon responsible for the generation of several chromosomal inversions in Drosophila. In contrast to other members of the P-element superfamily, it has unusually long terminal inverted-repeats (TIRs) that resemble those of Foldback elements. To investigate the function of the long TIRs we derived consensus and ancestral sequences for the Galileo transposase in three species of Drosophilids. Following gene synthesis, we expressed and purified their constituent THAP domains and tested their binding activity towards the respective Galileo TIRs. DNase I footprinting located the most proximal DNA binding site about 70 bp from the transposon end. Using this sequence we identified further binding sites in the tandem repeats that are found within the long TIRs. This suggests that the synaptic complex between Galileo ends may be a complicated structure containing higher-order multimers of the transposase. We also attempted to reconstitute Galileo transposition in Drosophila embryos but no events were detected. Thus, although the limited numbers of Galileo copies in each genome were sufficient to provide functional consensus sequences for the THAP domains, they do not specify a fully active transposase. Since the THAP recognition sequence is short, and will occur many times in a large genome, it seems likely that the multiple binding sites within the long, internally repetitive, TIRs of Galileo and other Foldback-like elements may provide the transposase with its binding specificity. Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.

Categorization in the Affective Domain

DEFF Research Database (Denmark)

Sauciuc, Gabriela-Alina

2011-01-01

Data collected in Romance and Scandinavian languages (N=474) in a superordinate category name production task indicate that a multiple-strategy approach would be more suitable for accounting of categorization in the affective domain instead of a prototype approach as suggested by previous studies....... This paper will highlight performance aspects which appear to be consistent with such an interpretation, as well as an important layman- expert knowledge asymmetry in affective categorization....

Multiple domains of social support are associated with diabetes self-management among Veterans.

Science.gov (United States)

Gray, Kristen E; Hoerster, Katherine D; Reiber, Gayle E; Bastian, Lori A; Nelson, Karin M

2018-01-01

Objectives To examine, among Veterans, relationships of general social support and diabetes-specific social support for physical activity and healthy eating with diabetes self-management behaviors. Methods Patients from VA Puget Sound, Seattle completed a cross-sectional survey in 2012-2013 ( N = 717). We measured (a) general social support and (b) diabetes-specific social support for healthy eating and physical activity with domains reflecting support person participation, encouragement, and sharing ideas. Among 189 self-reporting diabetes patients, we fit linear and modified Poisson regression models estimating associations of social support with diabetes self-management behaviors: adherence to general and diabetes-specific diets and blood glucose monitoring (days/week); physical activity (social support was not associated with diabetes self-management. For diabetes-specific social support, higher healthy eating support scores across all domains were associated with better adherence to general and diabetes-specific diets. Higher physical activity support scores were positively associated with ≥150 min/week of physical activity only for the participation domain. Discussion Diabetes-specific social support was a stronger and more consistent correlate of improved self-management than general social support, particularly for lifestyle behaviors. Incorporating family/friends into Veterans' diabetes self-management routines may lead to better self-management and improvements in disease control and outcomes.

Direct observation of stochastic domain-wall depinning in magnetic nanowires

Energy Technology Data Exchange (ETDEWEB)

Im, Mi-Young; Bocklage, Lars; Fischer, Peter; Meier, Guido

2008-11-01

The stochastic field-driven depinning of a domain wall pinned at a notch in a magnetic nanowire is directly observed using magnetic X-ray microscopy with high lateral resolution down to 15 nm. The depinning-field distribution in Ni{sub 80}Fe{sub 20} nanowires considerably depends on the wire width and the notch depth. The difference in the multiplicity of domain-wall types generated in the vicinity of a notch is responsible for the observed dependence of the stochastic nature of the domain wall depinning field on the wire width and the notch depth. Thus the random nature of the domain wall depinning process is controllable by an appropriate design of the nanowire.

Estimating Creativity with a Multiple-Measurement Approach within Scientific and Artistic Domains

Science.gov (United States)

Agnoli, Sergio; Corazza, Giovanni E.; Runco, Mark A.

2016-01-01

This article presents the structure and the composition of a newly developed multifaceted test battery for the measurement of creativity within scientific and artistic domains. By integrating existing procedures for the evaluation of creativity, the new battery promises to become a comprehensive assessment of creativity, encompassing both…

Catalytic properties of ADAM12 and its domain deletion mutants

DEFF Research Database (Denmark)

Jacobsen, Jonas; Visse, Robert; Sørensen, Hans Peter

2008-01-01

of pro, catalytic, disintegrin, cysteine-rich, and EGF domains. Here we present a novel activity of recombinant ADAM12-S and its domain deletion mutants on S-carboxymethylated transferrin (Cm-Tf). Cleavage of Cm-Tf occurred at multiple sites, and N-terminal sequencing showed that the enzyme exhibits...... restricted specificity but a consensus sequence could not be defined as its subsite requirements are promiscuous. Kinetic analysis revealed that the noncatalytic C-terminal domains are important regulators of Cm-Tf activity and that ADAM12-PC consisting of the pro domain and catalytic domain is the most...... active on this substrate. It was also observed that NaCl inhibits ADAM12. Among the tissue inhibitors of metalloproteinases (TIMP) examined, the N-terminal domain of TIMP-3 (N-TIMP-3) inhibits ADAM12-S and ADAM12-PC with low nanomolar Ki(app) values while TIMP-2 inhibits them with a slightly lower...

Assessment of perceptual diffuseness in the time domain

DEFF Research Database (Denmark)

Garcia, Julian Martinez-Villalba; Jeong, Cheol-Ho; Brunskog, Jonas

2017-01-01

This study proposes a numerical and experimental framework for evaluating the perceptual aspect of the diffuse field condition with intended final use in music auditoria. Multiple Impulse Responses are simulated based on the time domain Poisson process with increasing reflection density. Different...

Multiplicative Structure and Hecke Rings of Generator Matrices for Codes over Quotient Rings of Euclidean Domains

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Hajime Matsui

2017-12-01

Full Text Available In this study, we consider codes over Euclidean domains modulo their ideals. In the first half of the study, we deal with arbitrary Euclidean domains. We show that the product of generator matrices of codes over the rings mod a and mod b produces generator matrices of all codes over the ring mod a b , i.e., this correspondence is onto. Moreover, we show that if a and b are coprime, then this correspondence is one-to-one, i.e., there exist unique codes over the rings mod a and mod b that produce any given code over the ring mod a b through the product of their generator matrices. In the second half of the study, we focus on the typical Euclidean domains such as the rational integer ring, one-variable polynomial rings, rings of Gaussian and Eisenstein integers, p-adic integer rings and rings of one-variable formal power series. We define the reduced generator matrices of codes over Euclidean domains modulo their ideals and show their uniqueness. Finally, we apply our theory of reduced generator matrices to the Hecke rings of matrices over these Euclidean domains.

Multi-PAS domain-mediated protein oligomerization of PpsR from Rhodobacter sphaeroides

International Nuclear Information System (INIS)

Heintz, Udo; Meinhart, Anton; Winkler, Andreas

2014-01-01

Crystal structures of two truncated variants of the transcription factor PpsR from R. sphaeroides are presented that enabled the phasing of a triple PAS domain construct. Together, these structures reveal the importance of α-helical PAS extensions for multi-PAS domain-mediated protein oligomerization and function. Per–ARNT–Sim (PAS) domains are essential modules of many multi-domain signalling proteins that mediate protein interaction and/or sense environmental stimuli. Frequently, multiple PAS domains are present within single polypeptide chains, where their interplay is required for protein function. Although many isolated PAS domain structures have been reported over the last decades, only a few structures of multi-PAS proteins are known. Therefore, the molecular mechanism of multi-PAS domain-mediated protein oligomerization and function is poorly understood. The transcription factor PpsR from Rhodobacter sphaeroides is such a multi-PAS domain protein that, in addition to its three PAS domains, contains a glutamine-rich linker and a C-terminal helix–turn–helix DNA-binding motif. Here, crystal structures of two N-terminally and C-terminally truncated PpsR variants that comprise a single (PpsR Q-PAS1 ) and two (PpsR N-Q-PAS1 ) PAS domains, respectively, are presented and the multi-step strategy required for the phasing of a triple PAS domain construct (PpsR ΔHTH ) is illustrated. While parts of the biologically relevant dimerization interface can already be observed in the two shorter constructs, the PpsR ΔHTH structure reveals how three PAS domains enable the formation of multiple oligomeric states (dimer, tetramer and octamer), highlighting that not only the PAS cores but also their α-helical extensions are essential for protein oligomerization. The results demonstrate that the long helical glutamine-rich linker of PpsR results from a direct fusion of the N-cap of the PAS1 domain with the C-terminal extension of the N-domain that plays an important

Better verbal memory in women than men in MCI despite similar levels of hippocampal atrophy.

Science.gov (United States)

Sundermann, Erin E; Biegon, Anat; Rubin, Leah H; Lipton, Richard B; Mowrey, Wenzhu; Landau, Susan; Maki, Pauline M

2016-04-12

To examine sex differences in the relationship between clinical symptoms related to Alzheimer disease (AD) (verbal memory deficits) and neurodegeneration (hippocampal volume/intracranial volume ratio [HpVR]) across AD stages. The sample included 379 healthy participants, 694 participants with amnestic mild cognitive impairment (aMCI), and 235 participants with AD and dementia from the Alzheimer's Disease Neuroimaging Initiative who completed the Rey Auditory Verbal Learning Test (RAVLT). Cross-sectional analyses were conducted using linear regression to examine the interaction between sex and HpVR on RAVLT across and within diagnostic groups adjusting for age, education, and APOE ε4 status. Across groups, there were significant sex × HpVR interactions for immediate and delayed recall (p better RAVLT performance was independently associated with female sex (immediate, p = 0.04) and larger HpVR (delayed, p = 0.001). Women showed an advantage in verbal memory despite evidence of moderate hippocampal atrophy. This advantage may represent a sex-specific form of cognitive reserve delaying verbal memory decline until more advanced disease stages. © 2016 American Academy of Neurology.

Photon multiplicity measurements: From SPS to RHIC and LHC

Indian Academy of Sciences (India)

charged particle multiplicity, mean transverse momentum pT and transverse energy (ET)) ... by-event fluctuation in photon multiplicity and search for domains of ..... The root mean square (rms) deviations of theSZ distributions for data, mixed.

Social stigma and compounded losses: quality-of-life issues for multiple-birth families.

Science.gov (United States)

Ellison, Marcia A; Hall, Janet E

2003-08-01

To determine the quality-of-life domains most impacted by multiple births. Focus groups, qualitative research. Human volunteers in a medical research environment.Forty-three mothers, 29 raising multiple-birth children, 13 raising singletons, identified from random and convenience samples. None. Maternal self-reports of the psychosocial sequelae of multiple or singleton births, based on qualitative data analysis of transcribed group discussions. The quality-of-life domains that were most impacted by raising multiple birth children were social stigma, pregnancy loss, marital satisfaction, children's health, unmet family needs, parenting stress, maternal depression, and the infertility experience. Qualitative methods identified two novel quality-of-life domains in iatrogenic multiple birth families: social stigma and compounded losses. An unexpected finding was the potential for increased marital solidification as parents coped with the inordinate stresses of multiple births. As anticipated, children's health, unmet family needs, maternal depression, and parental stress were key areas of concern. In addition, the infertility experience had a lasting impact. These findings are significant, given that at least 38% of all assisted conceptions result in a multiple birth. This study lays the groundwork for further research on the impact of iatrogenic multiple births.

Recognizing mild cognitive impairment based on network connectivity analysis of resting EEG with zero reference

International Nuclear Information System (INIS)

Xu, Peng; Xiong, Xiu Chun; Tian, Yin; Zhang, Rui; Li, Pei Yang; Yao, De Zhong; Xue, Qing; Wang, Yu Ping; Peng, Yueheng

2014-01-01

The diagnosis of mild cognitive impairment (MCI) is very helpful for early therapeutic interventions of Alzheimer's disease (AD). MCI has been proven to be correlated with disorders in multiple brain areas. In this paper, we used information from resting brain networks at different EEG frequency bands to reliably recognize MCI. Because EEG network analysis is influenced by the reference that is used, we also evaluate the effect of the reference choices on the resting scalp EEG network-based MCI differentiation. The conducted study reveals two aspects: (1) the network-based MCI differentiation is superior to the previously reported classification that uses coherence in the EEG; and (2) the used EEG reference influences the differentiation performance, and the zero approximation technique (reference electrode standardization technique, REST) can construct a more accurate scalp EEG network, which results in a higher differentiation accuracy for MCI. This study indicates that the resting scalp EEG-based network analysis could be valuable for MCI recognition in the future. (paper)

Identifying Domain-General and Domain-Specific Predictors of Low Mathematics Performance: A Classification and Regression Tree Analysis

Directory of Open Access Journals (Sweden)

David J. Purpura

2017-12-01

Full Text Available Many children struggle to successfully acquire early mathematics skills. Theoretical and empirical evidence has pointed to deficits in domain-specific skills (e.g., non-symbolic mathematics skills or domain-general skills (e.g., executive functioning and language as underlying low mathematical performance. In the current study, we assessed a sample of 113 three- to five-year old preschool children on a battery of domain-specific and domain-general factors in the fall and spring of their preschool year to identify Time 1 (fall factors associated with low performance in mathematics knowledge at Time 2 (spring. We used the exploratory approach of classification and regression tree analyses, a strategy that uses step-wise partitioning to create subgroups from a larger sample using multiple predictors, to identify the factors that were the strongest classifiers of low performance for younger and older preschool children. Results indicated that the most consistent classifier of low mathematics performance at Time 2 was children’s Time 1 mathematical language skills. Further, other distinct classifiers of low performance emerged for younger and older children. These findings suggest that risk classification for low mathematics performance may differ depending on children’s age.

Processing complex pseudo-words in mild cognitive impairment: The interaction of preserved morphological rule knowledge with compromised cognitive ability.

Science.gov (United States)

Manouilidou, Christina; Dolenc, Barbara; Marvin, Tatjana; Pirtošek, Zvezdan

2016-01-01

Mild cognitive impairment (MCI) affects the cognitive performance of elderly adults. However, the level of severity is not high enough to be diagnosed with dementia. Previous research reports subtle language impairments in individuals with MCI specifically in domains related to lexical meaning. The present study used both off-line (grammaticality judgment) and on-line (lexical decision) tasks to examine aspects of lexical processing and how they are affected by MCI. 21 healthy older adults and 23 individuals with MCI saw complex pseudo-words that violated various principles of word formation in Slovenian and decided if each letter string was an actual word of their language. The pseudo-words ranged in their degree of violability. A task effect was found, with MCI performance to be similar to that of healthy controls in the off-line task but different in the on-line task. Overall, the MCI group responded slower than the elderly controls. No significant differences were observed in the off-line task, while the on-line task revealed a main effect of Violation type, a main effect of Group and a significant Violation × Group interaction reflecting a difficulty for the MCI group to process pseudo-words in real time. That is, while individuals with MCI seem to preserve morphological rule knowledge, they experience additional difficulties while processing complex pseudo-words. This was attributed to an executive dysfunction associated with MCI that delays the recognition of ungrammatical formations.

Impact of novelty and type of material on recognition in healthy older adults and persons with mild cognitive impairment.

Science.gov (United States)

Belleville, Sylvie; Ménard, Marie-Claude; Lepage, Emilie

2011-08-01

The goal of this study was to assess the effect of novelty on correct recognition (hit minus false alarms) and on recollection and familiarity processes in normal aging and amnestic mild cognitive impairment (MCI). Recognition tasks compared well-known and novel stimuli in the verbal domain (words vs. pseudowords) and in the musical domain (well-known vs. novel melodies). Results indicated that novel materials associated with lower correct recognition and lower recollection, an effect that can be related to its lower amenability to elaborative encoding in comparison with well-known items. Results also indicated that normal aging impairs recognition of well-known items, whereas MCI impairs recognition of novel items only. Healthy older adults showed impaired recollection and familiarity relative to younger controls and individuals with MCI showed impaired recollection relative to healthy older adults. The recollection deficit in healthy older adults and persons with MCI and their impaired recognition of well-known items is compatible with the difficulty both groups have in encoding information in an elaborate manner. In turn, familiarity deficit could be related to impaired frontal functioning. Therefore, novelty of material has a differential impact on recognition in persons with age-related memory disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Computational Identification of Genomic Features That Influence 3D Chromatin Domain Formation.

Science.gov (United States)

Mourad, Raphaël; Cuvier, Olivier

2016-05-01

Recent advances in long-range Hi-C contact mapping have revealed the importance of the 3D structure of chromosomes in gene expression. A current challenge is to identify the key molecular drivers of this 3D structure. Several genomic features, such as architectural proteins and functional elements, were shown to be enriched at topological domain borders using classical enrichment tests. Here we propose multiple logistic regression to identify those genomic features that positively or negatively influence domain border establishment or maintenance. The model is flexible, and can account for statistical interactions among multiple genomic features. Using both simulated and real data, we show that our model outperforms enrichment test and non-parametric models, such as random forests, for the identification of genomic features that influence domain borders. Using Drosophila Hi-C data at a very high resolution of 1 kb, our model suggests that, among architectural proteins, BEAF-32 and CP190 are the main positive drivers of 3D domain borders. In humans, our model identifies well-known architectural proteins CTCF and cohesin, as well as ZNF143 and Polycomb group proteins as positive drivers of domain borders. The model also reveals the existence of several negative drivers that counteract the presence of domain borders including P300, RXRA, BCL11A and ELK1.

Proof of Concept Integration of a Single-Level Service-Oriented Architecture into a Multi-Domain Secure Environment

National Research Council Canada - National Science Library

Gilkey, Craig M

2008-01-01

.... Such web services operating across multiple security domains would provide additional advantages, including improved intelligence aggregation, and real-time collaboration between users in different security domains...

A test of the domain-specific acculturation strategy hypothesis.

Science.gov (United States)

Miller, Matthew J; Yang, Minji; Lim, Robert H; Hui, Kayi; Choi, Na-Yeun; Fan, Xiaoyan; Lin, Li-Ling; Grome, Rebekah E; Farrell, Jerome A; Blackmon, Sha'kema

2013-01-01

Acculturation literature has evolved over the past several decades and has highlighted the dynamic ways in which individuals negotiate experiences in multiple cultural contexts. The present study extends this literature by testing M. J. Miller and R. H. Lim's (2010) domain-specific acculturation strategy hypothesis-that individuals might use different acculturation strategies (i.e., assimilated, bicultural, separated, and marginalized strategies; J. W. Berry, 2003) across behavioral and values domains-in 3 independent cluster analyses with Asian American participants. Present findings supported the domain-specific acculturation strategy hypothesis as 67% to 72% of participants from 3 independent samples using different strategies across behavioral and values domains. Consistent with theory, a number of acculturation strategy cluster group differences emerged across generational status, acculturative stress, mental health symptoms, and attitudes toward seeking professional psychological help. Study limitations and future directions for research are discussed.

Design of Xen Hybrid Multiple Police Model

Science.gov (United States)

Sun, Lei; Lin, Renhao; Zhu, Xianwei

2017-10-01

Virtualization Technology has attracted more and more attention. As a popular open-source virtualization tools, XEN is used more and more frequently. Xsm, XEN security model, has also been widespread concern. The safety status classification has not been established in the XSM, and it uses the virtual machine as a managed object to make Dom0 a unique administrative domain that does not meet the minimum privilege. According to these questions, we design a Hybrid multiple police model named SV_HMPMD that organically integrates multiple single security policy models include DTE,RBAC,BLP. It can fullfill the requirement of confidentiality and integrity for security model and use different particle size to different domain. In order to improve BLP’s practicability, the model introduce multi-level security labels. In order to divide the privilege in detail, we combine DTE with RBAC. In order to oversize privilege, we limit the privilege of domain0.

Spatial working memory in aging and mild cognitive impairment: effects of task load and contextual cueing.

Science.gov (United States)

Kessels, Roy P C; Meulenbroek, Olga; Fernández, Guillén; Olde Rikkert, Marcel G M

2010-09-01

Mild Cognitive Impairment (MCI) is characterized by episodic memory deficits, while aspects of working memory may also be implicated, but studies into this latter domain are scarce and results are inconclusive. Using a computerized search paradigm, this study compares 25 young adults, 25 typically aging older adults and 15 amnestic MCI patients as to their working-memory capacities for object-location information and potential differential effects of memory load and additional context cues. An age-related deficit in visuospatial working-memory maintenance was found that became more pronounced with increasing task demands. The MCI group additionally showed reduced maintenance of bound information, i.e., object-location associations, again especially at elevated memory load. No effects of contextual cueing were found. The current findings indicate that working memory should be considered when screening patients for suspected MCI and monitoring its progression.

MULTIPLE OBJECTS

Directory of Open Access Journals (Sweden)

A. A. Bosov

2015-04-01

Full Text Available Purpose. The development of complicated techniques of production and management processes, information systems, computer science, applied objects of systems theory and others requires improvement of mathematical methods, new approaches for researches of application systems. And the variety and diversity of subject systems makes necessary the development of a model that generalizes the classical sets and their development – sets of sets. Multiple objects unlike sets are constructed by multiple structures and represented by the structure and content. The aim of the work is the analysis of multiple structures, generating multiple objects, the further development of operations on these objects in application systems. Methodology. To achieve the objectives of the researches, the structure of multiple objects represents as constructive trio, consisting of media, signatures and axiomatic. Multiple object is determined by the structure and content, as well as represented by hybrid superposition, composed of sets, multi-sets, ordered sets (lists and heterogeneous sets (sequences, corteges. Findings. In this paper we study the properties and characteristics of the components of hybrid multiple objects of complex systems, proposed assessments of their complexity, shown the rules of internal and external operations on objects of implementation. We introduce the relation of arbitrary order over multiple objects, we define the description of functions and display on objects of multiple structures. Originality.In this paper we consider the development of multiple structures, generating multiple objects.Practical value. The transition from the abstract to the subject of multiple structures requires the transformation of the system and multiple objects. Transformation involves three successive stages: specification (binding to the domain, interpretation (multiple sites and particularization (goals. The proposed describe systems approach based on hybrid sets

Multiple solutions for inhomogeneous nonlinear elliptic problems arising in astrophyiscs

Directory of Open Access Journals (Sweden)

Marco Calahorrano

2004-04-01

Full Text Available Using variational methods we prove the existence and multiplicity of solutions for some nonlinear inhomogeneous elliptic problems on a bounded domain in $mathbb{R}^n$, with $ngeq 2$ and a smooth boundary, and when the domain is $mathbb{R}_+^n$

Step by Step: Biology Undergraduates’ Problem-Solving Procedures during Multiple-Choice Assessment

Science.gov (United States)

Prevost, Luanna B.; Lemons, Paula P.

2016-01-01

This study uses the theoretical framework of domain-specific problem solving to explore the procedures students use to solve multiple-choice problems about biology concepts. We designed several multiple-choice problems and administered them on four exams. We trained students to produce written descriptions of how they solved the problem, and this allowed us to systematically investigate their problem-solving procedures. We identified a range of procedures and organized them as domain general, domain specific, or hybrid. We also identified domain-general and domain-specific errors made by students during problem solving. We found that students use domain-general and hybrid procedures more frequently when solving lower-order problems than higher-order problems, while they use domain-specific procedures more frequently when solving higher-order problems. Additionally, the more domain-specific procedures students used, the higher the likelihood that they would answer the problem correctly, up to five procedures. However, if students used just one domain-general procedure, they were as likely to answer the problem correctly as if they had used two to five domain-general procedures. Our findings provide a categorization scheme and framework for additional research on biology problem solving and suggest several important implications for researchers and instructors. PMID:27909021

Amyloid-independent functional neural correlates of episodic memory in amnestic mild cognitive impairment.

Science.gov (United States)

Seo, Eun Hyun; Choo, I L Han

2016-06-01

Although amnestic mild cognitive impairment (aMCI) could have various biological characteristics, little attention has been given to the nature of episodic memory decline in aMCI with pathophysiologies other than Alzheimer's disease (AD), i.e., aMCI with low beta-amyloid (Aβ) burden. This study aimed to identify the functional neural basis of episodic memory impairment in aMCI with Aβ burden negative (aMCI-Aβ-) and to compare these results with aMCI with Aβ burden positive (aMCI-Aβ+). Individuals with aMCI (n = 498) were selected from the Alzheimer's Disease Neuroimaging Initiative database. Based on the mean florbetapir standard uptake value ratio, participants were classified as aMCI-Aβ- or aMCI-Aβ+. Correlations between memory scores and regional cerebral glucose metabolism (rCMglc) were analyzed separately for the two subgroups using a multiple regression model. For aMCI-Aβ-, significant positive correlations between memory and rCMglc were found in the bilateral claustrum, right thalamus, left anterior cingulate cortex, left insula, and right posterior cingulate. For aMCI-Aβ+, significant positive correlations between memory and rCMglc were found in the temporoparietal areas. These correlation patterns remained unchanged when clinical severity was added as a covariate Our findings indicate that memory impairment in aMCI-Aβ- is related to multimodal integrative processing and the attentional control system, whereas memory impairment in aMCI-Aβ+ is related to the typical brain memory systems and AD signature. These results suggest that although the two subgroups are clinically in the same category as aMCI, the memory impairment process depends on completely different functional brain regions according to their Aβ burden level.

A Bayesian Sampler for Optimization of Protein Domain Hierarchies

Science.gov (United States)

2014-01-01

Abstract The process of identifying and modeling functionally divergent subgroups for a specific protein domain class and arranging these subgroups hierarchically has, thus far, largely been done via manual curation. How to accomplish this automatically and optimally is an unsolved statistical and algorithmic problem that is addressed here via Markov chain Monte Carlo sampling. Taking as input a (typically very large) multiple-sequence alignment, the sampler creates and optimizes a hierarchy by adding and deleting leaf nodes, by moving nodes and subtrees up and down the hierarchy, by inserting or deleting internal nodes, and by redefining the sequences and conserved patterns associated with each node. All such operations are based on a probability distribution that models the conserved and divergent patterns defining each subgroup. When we view these patterns as sequence determinants of protein function, each node or subtree in such a hierarchy corresponds to a subgroup of sequences with similar biological properties. The sampler can be applied either de novo or to an existing hierarchy. When applied to 60 protein domains from multiple starting points in this way, it converged on similar solutions with nearly identical log-likelihood ratio scores, suggesting that it typically finds the optimal peak in the posterior probability distribution. Similarities and differences between independently generated, nearly optimal hierarchies for a given domain help distinguish robust from statistically uncertain features. Thus, a future application of the sampler is to provide confidence measures for various features of a domain hierarchy. PMID:24494927

Attenuation of multiples in image space

Science.gov (United States)

Alvarez, Gabriel F.

In complex subsurface areas, attenuation of 3D specular and diffracted multiples in data space is difficult and inaccurate. In those areas, image space is an attractive alternative. There are several reasons: (1) migration increases the signal-to-noise ratio of the data; (2) primaries are mapped to coherent events in Subsurface Offset Domain Common Image Gathers (SODCIGs) or Angle Domain Common Image Gathers (ADCIGs); (3) image space is regular and smaller; (4) attenuating the multiples in data space leaves holes in the frequency-Wavenumber space that generate artifacts after migration. I develop a new equation for the residual moveout of specular multiples in ADCIGs and use it for the kernel of an apex-shifted Radon transform to focus and separate the primaries from specular and diffracted multiples. Because of small amplitude, phase and kinematic errors in the multiple estimate, we need adaptive matching and subtraction to estimate the primaries. I pose this problem as an iterative least-squares inversion that simultaneously matches the estimates of primaries and multiples to the data. Standard methods match only the estimate of the multiples. I demonstrate with real and synthetic data that the method produces primaries and multiples with little cross-talk. In 3D, the multiples exhibit residual moveout in SODCIGs in in-line and cross-line offsets. They map away from zero subsurface offsets when migrated with the faster velocity of the primaries. In ADCIGs the residual moveout of the primaries as a function of the aperture angle, for a given azimuth, is flat for those angles that illuminate the reflector. The multiples have residual moveout towards increasing depth for increasing aperture angles at all azimuths. As a function of azimuth, the primaries have better azimuth resolution than the multiples at larger aperture angles. I show, with a real 3D dataset, that even below salt, where illumination is poor, the multiples are well attenuated in ADCIGs with the new

Efficient Adoption and Assessment of Multiple Process Improvement Reference Models

Directory of Open Access Journals (Sweden)

Simona Jeners

2013-06-01

Full Text Available A variety of reference models such as CMMI, COBIT or ITIL support IT organizations to improve their processes. These process improvement reference models (IRMs cover different domains such as IT development, IT Services or IT Governance but also share some similarities. As there are organizations that address multiple domains and need to coordinate their processes in their improvement we present MoSaIC, an approach to support organizations to efficiently adopt and conform to multiple IRMs. Our solution realizes a semantic integration of IRMs based on common meta-models. The resulting IRM integration model enables organizations to efficiently implement and asses multiple IRMs and to benefit from synergy effects.

Global efficiency of structural networks mediates cognitive control in Mild Cognitive Impairment

Directory of Open Access Journals (Sweden)

Rok Berlot

2016-12-01

Full Text Available Background: Cognitive control has been linked to both the microstructure of individual tracts and the structure of whole-brain networks, but their relative contributions in health and disease remain unclear. Objective: To determine the contribution of both localised white matter tract damage and disruption of global network architecture to cognitive control, in older age and Mild Cognitive Impairment (MCI.Methods: 25 patients with MCI and 20 age, sex and intelligence-matched healthy volunteers were investigated with 3 Tesla structural magnetic resonance imaging (MRI. Cognitive control and episodic memory were evaluated with established tests. Structural network graphs were constructed from diffusion MRI-based whole-brain tractography. Their global measures were calculated using graph theory. Regression models utilized both global network metrics and microstructure of specific connections, known to be critical for each domain, to predict cognitive scores. Results: Global efficiency and the mean clustering coefficient of networks were reduced in MCI. Cognitive control was associated with global network topology. Episodic memory, in contrast, correlated with individual temporal tracts only. Relationships between cognitive control and network topology were attenuated by addition of single tract measures to regression models, consistent with a partial mediation effect. The mediation effect was stronger in MCI than healthy volunteers, explaining 23-36% of the effect of cingulum microstructure on cognitive control performance. Network clustering was a significant mediator in the relationship between tract microstructure and cognitive control in both groups. Conclusions: The status of critical connections and large-scale network topology are both important for maintenance of cognitive control in MCI. Mediation via large-scale networks is more important in patients with MCI than healthy volunteers. This effect is domain-specific, and true for cognitive

Addenbrooke’s Cognitive Examination and Individual Domain Cut-Off Scores for Discriminating between Different Cognitive Subtypes of Parkinson’s Disease

OpenAIRE

Dagmar Berankova; Eva Janousova; Martina Mrackova; Ilona Eliasova; Milena Kostalova; Svetlana Skutilova; Irena Rektorova

2015-01-01

Objective. The main aim of this study was to verify the sensitivity and specificity of Addenbrooke's Cognitive Examination-Revised (ACE-R) in discriminating between Parkinson's disease (PD) with normal cognition (PD-NC) and PD with mild cognitive impairment (PD-MCI) and between PD-MCI and PD with dementia (PD-D). We also evaluated how ACE-R correlates with neuropsychological cognitive tests in PD. Methods. We examined three age-matched groups of PD patients diagnosed according to the Movement...

Regression Models for Market-Shares

DEFF Research Database (Denmark)

Birch, Kristina; Olsen, Jørgen Kai; Tjur, Tue

2005-01-01

On the background of a data set of weekly sales and prices for three brands of coffee, this paper discusses various regression models and their relation to the multiplicative competitive-interaction model (the MCI model, see Cooper 1988, 1993) for market-shares. Emphasis is put on the interpretat......On the background of a data set of weekly sales and prices for three brands of coffee, this paper discusses various regression models and their relation to the multiplicative competitive-interaction model (the MCI model, see Cooper 1988, 1993) for market-shares. Emphasis is put...... on the interpretation of the parameters in relation to models for the total sales based on discrete choice models.Key words and phrases. MCI model, discrete choice model, market-shares, price elasitcity, regression model....

Experimental demonstration of multiple-inputs multiple-outputs OFDM/OQAM visible light communications

Science.gov (United States)

Lin, Bangjiang; Tang, Xuan; Ghassemlooy, Zabih; Lin, Chun; Zhang, Min

2017-10-01

We experimentally demonstrate a 2×2 optical multiple-inputs multiple-outputs (MIMO) visible light communications system based on the modified orthogonal frequency-division multiplexing/offset quadrature amplitude modulation scheme. The adjacent subcarrier frequency-domain averaging (ASFA) with the full-loaded (FL) and half-loaded (HL) preamble structures is proposed for demultiplexing and mitigating the intrinsic imaginary interference (IMI) effect. Compared with the conventional channel estimation (CE) method, ASFA offers improved transmission performance. With the FL method, we obtain more accurate MIMO CE to mitigate the IMI effect and the optical noise compared to the HL method.

Screening retinal transplants with Fourier-domain OCT

Science.gov (United States)

Rao, Bin

2009-02-01

Transplant technologies have been studied for the recovery of vision loss from retinitis pigmentosa (RP) and age-related macular degeneration (AMD). In several rodent retinal degeneration models and in patients, retinal progenitor cells transplanted as layers to the subretinal space have been shown to restore or preserve vision. The methods for evaluation of transplants are expensive considering the large amount of animals. Alternatively, time-domain Stratus OCT was previously shown to be able to image the morphological structure of transplants to some extent, but could not clearly identify laminated transplants. The efficacy of screening retinal transplants with Fourier-domain OCT was studied on 37 S334ter line 3 rats with retinal degeneration 6-67 days after transplant surgery. The transplants were morphologically categorized as no transplant, detachment, rosettes, small laminated area and larger laminated area with both Fourier-domain OCT and histology. The efficacy of Fourier-domain OCT in screening retinal transplants was evaluated by comparing the categorization results with OCT and histology. Additionally, 4 rats were randomly selected for multiple OCT examinations (1, 5, 9, 14 and 21days post surgery) in order to determine the earliest image time of OCT examination since the transplanted tissue may need some time to show its tendency of growing. Finally, we demonstrated the efficacy of Fourier-domain OCT in screening retinal transplants in early stages and determined the earliest imaging time for OCT. Fourier-domain OCT makes itself valuable in saving resource spent on animals with unsuccessful transplants.

Anosognosia for cognitive and behavioral symptoms in Parkinson's disease with mild dementia and mild cognitive impairment: Frequency and neuropsychological/neuropsychiatric correlates.

Science.gov (United States)

Orfei, Maria Donata; Assogna, Francesca; Pellicano, Clelia; Pontieri, Francesco Ernesto; Caltagirone, Carlo; Pierantozzi, Mariangela; Stefani, Alessandro; Spalletta, Gianfranco

2018-04-17

Anosognosia is a multidimensional phenomenon with detrimental effects on patients' illness course, therapy compliance and quality of life. We aimed at investigating anosognosia for cognitive and behavioral symptoms in Parkinson's Disease (PD) with dementia (PDD) and, for the first time, in PD with Mild Cognitive Impairment (MCI-PD). Community dwelling subjects (47 mild PDD, 136 multidomain MCI-PD (mdMCI-PD), 5 single domain MCI-PD (sdMCI-PD), and 197 PD without cognitive impairment (noCI-PD) were enrolled in a cross-sectional design study. All the subjects were administered the Anosognosia Questionnaire for Dementia, the Mental Deterioration Battery and a number of neuropsychiatric inventories. A diagnosis of anosognosia was made in 36% of patients with mild PDD and 16% with mdMCI-PD, whether it was negligible in sdMCI-PD and noCI-PD. Higher severity of anosognosia for cognitive impairment was also found in PDD and in mdMCI-PD. SdMCI-PD had the lower severity of anosognosia for cognitive impairment. Higher anosognosia for cognitive impairment was associated to lower depression in noCI-PD (r = -0.227, p = 0.0013) and mdMCI-PD (r = -0.266, p = 0.0016), and to reduced hedonic tone in noCI-PD (r = -0.191, p = 0.0071). Greater anosognosia was associated to lower executive performances in PDD (r = 0.424, p = 0.0074). Anosognosia for non-motor symptoms is frequent in PD patients with mild dementia or mdMCI. Results confirm the role of neuropsychiatric characteristics in anosognosia also in PD, the high prevalence of anosognosia in neurodegenerative illnesses and suggest a common pathogenic path for anosognosia in different neurodegenerative and psychiatric disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

The neuroimaging approach to the assessment of mild cognitive impairment

International Nuclear Information System (INIS)

Lucignani, Giovanni

2006-01-01

Imaging techniques, including emission tomography and magnetic resonance imaging, are progressively being exploited for the classification and prognostic evaluation (indispensable for possible treatments) of mild cognitive impairment (MCI). The main traits of MCI and unsolved issues in its assessment are discussed in two review articles by Feldman and Jacova from the Division of Neurology, Dept. of Medicine, Clinic for Alzheimer Disease and Related Disorders, University of British Columbia, in Vancouver, Canada [1] and Chong and Sahadevan from the Department of Geriatric Medicine, Tan Tock Seng Hospital, Jalan Tan Tock Seng, Singapore [2]. Because MCI has different presentations in terms of the type and degree of cognitive deficits observed, several clinical subtypes of MCI besides the amnestic form have now been recognised and characterised on the basis of deficits in different cognitive domains, either in isolation or in combination with amnesia. The different subtypes of MCI suggest that MCI has a heterogeneous nature, with several possible causes that lead to the same symptoms. This is a field in evolution, and a uniform diagnostic classification of MCI has not yet been accomplished. Lopez et al. from the Departments of Neurology and Psychiatry, University of Pittsburgh, School of Medicine,Pittsburgh, Pennsylvania, USA [3] point out that the classification of MCI subtypes is useful to improve prediction of the subsequent risk of dementia and the type of dementia, and that the manner in which MCI subjects are classified into subgroups has implications for the cognitive profile of the group and thus for our inferences about the aetiology and possible clinical course of the disorder

The neuroimaging approach to the assessment of mild cognitive impairment

Energy Technology Data Exchange (ETDEWEB)

Lucignani, Giovanni [University of Milan and Unit of Molecular Imaging, Division of Radiation Therapy, European Institute of Oncology, Institute of Radiological Sciences, Milan (Italy)

2006-06-15

Imaging techniques, including emission tomography and magnetic resonance imaging, are progressively being exploited for the classification and prognostic evaluation (indispensable for possible treatments) of mild cognitive impairment (MCI). The main traits of MCI and unsolved issues in its assessment are discussed in two review articles by Feldman and Jacova from the Division of Neurology, Dept. of Medicine, Clinic for Alzheimer Disease and Related Disorders, University of British Columbia, in Vancouver, Canada [1] and Chong and Sahadevan from the Department of Geriatric Medicine, Tan Tock Seng Hospital, Jalan Tan Tock Seng, Singapore [2]. Because MCI has different presentations in terms of the type and degree of cognitive deficits observed, several clinical subtypes of MCI besides the amnestic form have now been recognised and characterised on the basis of deficits in different cognitive domains, either in isolation or in combination with amnesia. The different subtypes of MCI suggest that MCI has a heterogeneous nature, with several possible causes that lead to the same symptoms. This is a field in evolution, and a uniform diagnostic classification of MCI has not yet been accomplished. Lopez et al. from the Departments of Neurology and Psychiatry, University of Pittsburgh, School of Medicine,Pittsburgh, Pennsylvania, USA [3] point out that the classification of MCI subtypes is useful to improve prediction of the subsequent risk of dementia and the type of dementia, and that the manner in which MCI subjects are classified into subgroups has implications for the cognitive profile of the group and thus for our inferences about the aetiology and possible clinical course of the disorder.

Automated vessel shadow segmentation of fovea-centered spectral-domain images from multiple OCT devices

Science.gov (United States)

Wu, Jing; Gerendas, Bianca S.; Waldstein, Sebastian M.; Simader, Christian; Schmidt-Erfurth, Ursula

2014-03-01

Spectral-domain Optical Coherence Tomography (SD-OCT) is a non-invasive modality for acquiring high reso- lution, three-dimensional (3D) cross sectional volumetric images of the retina and the subretinal layers. SD-OCT also allows the detailed imaging of retinal pathology, aiding clinicians in the diagnosis of sight degrading diseases such as age-related macular degeneration (AMD) and glaucoma.1 Disease diagnosis, assessment, and treatment requires a patient to undergo multiple OCT scans, possibly using different scanning devices, to accurately and precisely gauge disease activity, progression and treatment success. However, the use of OCT imaging devices from different vendors, combined with patient movement may result in poor scan spatial correlation, potentially leading to incorrect patient diagnosis or treatment analysis. Image registration can be used to precisely compare disease states by registering differing 3D scans to one another. In order to align 3D scans from different time- points and vendors using registration, landmarks are required, the most obvious being the retinal vasculature. Presented here is a fully automated cross-vendor method to acquire retina vessel locations for OCT registration from fovea centred 3D SD-OCT scans based on vessel shadows. Noise filtered OCT scans are flattened based on vendor retinal layer segmentation, to extract the retinal pigment epithelium (RPE) layer of the retina. Voxel based layer profile analysis and k-means clustering is used to extract candidate vessel shadow regions from the RPE layer. In conjunction, the extracted RPE layers are combined to generate a projection image featuring all candidate vessel shadows. Image processing methods for vessel segmentation of the OCT constructed projection image are then applied to optimize the accuracy of OCT vessel shadow segmentation through the removal of false positive shadow regions such as those caused by exudates and cysts. Validation of segmented vessel shadows uses

Everyday episodic memory in amnestic mild cognitive impairment: a preliminary investigation

OpenAIRE

LAWLOR, BRIAN; COEN, ROBERT; O'MARA, SHANE MICHAEL

2011-01-01

PUBLISHED Background: Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impa...

Everyday episodic memory in amnestic mild cognitive impairment: a preliminary investigation

OpenAIRE

Irish, Muireann; Lawlor, Brian A; Coen, Robert F; O'Mara, Shane M

2011-01-01

Abstract Background Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impact of di...

Coherent combining pulse bursts in time domain

Science.gov (United States)

Galvanauskas, Almantas

2018-01-09

A beam combining and pulse stacking technique is provided that enhances laser pulse energy by coherent stacking pulse bursts (i.e. non-periodic pulsed signals) in time domain. This energy enhancement is achieved by using various configurations of Fabry-Perot, Gires-Tournois and other types of resonant cavities, so that a multiple-pulse burst incident at either a single input or multiple inputs of the system produces an output with a solitary pulse, which contains the summed energy of the incident multiple pulses from all beams. This disclosure provides a substantial improvement over conventional coherent-combining methods in that it achieves very high pulse energies using a relatively small number of combined laser systems, thus providing with orders of magnitude reduction in system size, complexity, and cost compared to current combining approaches.

Cognitive and imaging markers in non-demented subjects attending a memory clinic: study design and baseline findings of the MEMENTO cohort.

Science.gov (United States)

Dufouil, Carole; Dubois, Bruno; Vellas, Bruno; Pasquier, Florence; Blanc, Frédéric; Hugon, Jacques; Hanon, Olivier; Dartigues, Jean-François; Harston, Sandrine; Gabelle, Audrey; Ceccaldi, Mathieu; Beauchet, Olivier; Krolak-Salmon, Pierre; David, Renaud; Rouaud, Olivier; Godefroy, Olivier; Belin, Catherine; Rouch, Isabelle; Auguste, Nicolas; Wallon, David; Benetos, Athanase; Pariente, Jérémie; Paccalin, Marc; Moreaud, Olivier; Hommet, Caroline; Sellal, François; Boutoleau-Bretonniére, Claire; Jalenques, Isabelle; Gentric, Armelle; Vandel, Pierre; Azouani, Chabha; Fillon, Ludovic; Fischer, Clara; Savarieau, Helen; Operto, Gregory; Bertin, Hugo; Chupin, Marie; Bouteloup, Vincent; Habert, Marie-Odile; Mangin, Jean-François; Chêne, Geneviève

2017-08-29

The natural history and disease mechanisms of Alzheimer's disease and related disorders (ADRD) are still poorly understood. Very few resources are available to scrutinise patients as early as needed and to use integrative approaches combining standardised, repeated clinical investigations and cutting-edge biomarker measurements. In the nationwide French MEMENTO cohort study, participants were recruited in memory clinics and screened for either isolated subjective cognitive complaints (SCCs) or mild cognitive impairment (MCI; defined as test performance 1.5 SD below age, sex and education-level norms) while not demented (Clinical Dementia Rating [CDR] <1). Baseline data collection included neurological and physical examinations as well as extensive neuropsychological testing. To be included in the MEMENTO cohort, participants had to agree to undergo both brain magnetic resonance imaging (MRI) and blood sampling. Cerebral 18 F-fluorodeoxyglucose positon emission tomography and lumbar puncture were optional. Automated analyses of cerebral MRI included assessments of volumes of whole-brain, hippocampal and white matter lesions. The 2323 participants, recruited from April 2011 to June 2014, were aged 71 years, on average (SD 8.7), and 62% were women. CDR was 0 in 40% of participants, and 30% carried at least one apolipoprotein E ε4 allele. We observed that more than half (52%) of participants had amnestic mild cognitive impairment (17% single-domain aMCI), 32% had non-amnestic mild cognitive impairment (16.9% single-domain naMCI) and 16% had isolated SCCs. Multivariable analyses of neuroimaging markers associations with cognitive categories showed that participants with aMCI had worse levels of imaging biomarkers than the others, whereas participants with naMCI had markers at intermediate levels between SCC and aMCI. The burden of white matter lesions tended to be larger in participants with aMCI. Independently of CDR, all neuroimaging and neuropsychological markers

Fine Motor Function Skills in Patients with Parkinson Disease with and without Mild Cognitive Impairment.

Science.gov (United States)

Dahdal, Philippe; Meyer, Antonia; Chaturvedi, Menorca; Nowak, Karolina; Roesch, Anne D; Fuhr, Peter; Gschwandtner, Ute

2016-01-01

The objective of this study was to investigate the relation between impaired fine motor skills in Parkinson disease (PD) patients and their cognitive status, and to determine whether fine motor skills are more impaired in PD patients with mild cognitive impairment (MCI) than in non-MCI patients. Twenty PD MCI and 31 PD non-MCI patients (mean age 66.7 years, range 50-84, 36 males/15 females), all right-handed, took part in a motor performance test battery. Steadiness, precision, dexterity, velocity of arm-hand movements, and velocity of wrist-finger movements were measured and compared across groups and analyzed for confounders (age, sex, education, severity of motor symptoms, and disease duration). Statistical analysis included t tests corrected for multiple testing, and a linear regression with stepwise elimination procedure was used to select significant predictors for fine motor function. PD MCI patients performed significantly worse in precision (p motor function skills were confounded by age. Fine motor skills in PD MCI patients are impaired compared to PD non-MCI patients. Investigating the relation between the fine motor performance and MCI in PD might be a relevant subject for future research. © 2016 S. Karger AG, Basel.

Method and Apparatus of Multiplexing and Acquiring Data from Multiple Optical Fibers Using a Single Data Channel of an Optical Frequency-Domain Reflectometry (OFDR) System

Science.gov (United States)

Parker, Jr., Allen R (Inventor); Chan, Hon Man (Inventor); Piazza, Anthony (Nino) (Inventor); Richards, William Lance (Inventor)

2014-01-01

A method and system for multiplexing a network of parallel fiber Bragg grating (FBG) sensor-fibers to a single acquisition channel of a closed Michelson interferometer system via a fiber splitter by distinguishing each branch of fiber sensors in the spatial domain. On each branch of the splitter, the fibers have a specific pre-determined length, effectively separating each branch of fiber sensors spatially. In the spatial domain the fiber branches are seen as part of one acquisition channel on the interrogation system. However, the FBG-reference arm beat frequency information for each fiber is retained. Since the beat frequency is generated between the reference arm, the effective fiber length of each successive branch includes the entire length of the preceding branch. The multiple branches are seen as one fiber having three segments where the segments can be resolved. This greatly simplifies optical, electronic and computational complexity, and is especially suited for use in multiplexed or branched OFS networks for SHM of large and/or distributed structures which need a lot of measurement points.

Hybrid approaches for multiple-species stochastic reaction–diffusion models

International Nuclear Information System (INIS)

Spill, Fabian; Guerrero, Pilar; Alarcon, Tomas; Maini, Philip K.; Byrne, Helen

2015-01-01

Reaction–diffusion models are used to describe systems in fields as diverse as physics, chemistry, ecology and biology. The fundamental quantities in such models are individual entities such as atoms and molecules, bacteria, cells or animals, which move and/or react in a stochastic manner. If the number of entities is large, accounting for each individual is inefficient, and often partial differential equation (PDE) models are used in which the stochastic behaviour of individuals is replaced by a description of the averaged, or mean behaviour of the system. In some situations the number of individuals is large in certain regions and small in others. In such cases, a stochastic model may be inefficient in one region, and a PDE model inaccurate in another. To overcome this problem, we develop a scheme which couples a stochastic reaction–diffusion system in one part of the domain with its mean field analogue, i.e. a discretised PDE model, in the other part of the domain. The interface in between the two domains occupies exactly one lattice site and is chosen such that the mean field description is still accurate there. In this way errors due to the flux between the domains are small. Our scheme can account for multiple dynamic interfaces separating multiple stochastic and deterministic domains, and the coupling between the domains conserves the total number of particles. The method preserves stochastic features such as extinction not observable in the mean field description, and is significantly faster to simulate on a computer than the pure stochastic model. - Highlights: • A novel hybrid stochastic/deterministic reaction–diffusion simulation method is given. • Can massively speed up stochastic simulations while preserving stochastic effects. • Can handle multiple reacting species. • Can handle moving boundaries

Hybrid approaches for multiple-species stochastic reaction–diffusion models

Energy Technology Data Exchange (ETDEWEB)

Spill, Fabian, E-mail: fspill@bu.edu [Department of Biomedical Engineering, Boston University, 44 Cummington Street, Boston, MA 02215 (United States); Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 (United States); Guerrero, Pilar [Department of Mathematics, University College London, Gower Street, London WC1E 6BT (United Kingdom); Alarcon, Tomas [Centre de Recerca Matematica, Campus de Bellaterra, Edifici C, 08193 Bellaterra (Barcelona) (Spain); Departament de Matemàtiques, Universitat Atonòma de Barcelona, 08193 Bellaterra (Barcelona) (Spain); Maini, Philip K. [Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford OX2 6GG (United Kingdom); Byrne, Helen [Wolfson Centre for Mathematical Biology, Mathematical Institute, University of Oxford, Oxford OX2 6GG (United Kingdom); Computational Biology Group, Department of Computer Science, University of Oxford, Oxford OX1 3QD (United Kingdom)

2015-10-15

Reaction–diffusion models are used to describe systems in fields as diverse as physics, chemistry, ecology and biology. The fundamental quantities in such models are individual entities such as atoms and molecules, bacteria, cells or animals, which move and/or react in a stochastic manner. If the number of entities is large, accounting for each individual is inefficient, and often partial differential equation (PDE) models are used in which the stochastic behaviour of individuals is replaced by a description of the averaged, or mean behaviour of the system. In some situations the number of individuals is large in certain regions and small in others. In such cases, a stochastic model may be inefficient in one region, and a PDE model inaccurate in another. To overcome this problem, we develop a scheme which couples a stochastic reaction–diffusion system in one part of the domain with its mean field analogue, i.e. a discretised PDE model, in the other part of the domain. The interface in between the two domains occupies exactly one lattice site and is chosen such that the mean field description is still accurate there. In this way errors due to the flux between the domains are small. Our scheme can account for multiple dynamic interfaces separating multiple stochastic and deterministic domains, and the coupling between the domains conserves the total number of particles. The method preserves stochastic features such as extinction not observable in the mean field description, and is significantly faster to simulate on a computer than the pure stochastic model. - Highlights: • A novel hybrid stochastic/deterministic reaction–diffusion simulation method is given. • Can massively speed up stochastic simulations while preserving stochastic effects. • Can handle multiple reacting species. • Can handle moving boundaries.

The conserved Tarp actin binding domain is important for chlamydial invasion.

Directory of Open Access Journals (Sweden)

Travis J Jewett

2010-07-01

Full Text Available The translocated actin recruiting phosphoprotein (Tarp is conserved among all pathogenic chlamydial species. Previous reports identified single C. trachomatis Tarp actin binding and proline rich domains required for Tarp mediated actin nucleation. A peptide antiserum specific for the Tarp actin binding domain was generated and inhibited actin polymerization in vitro and C. trachomatis entry in vivo, indicating an essential role for Tarp in chlamydial pathogenesis. Sequence analysis of Tarp orthologs from additional chlamydial species and C. trachomatis serovars indicated multiple putative actin binding sites. In order to determine whether the identified actin binding domains are functionally conserved, GST-Tarp fusions from multiple chlamydial species were examined for their ability to bind and nucleate actin. Chlamydial Tarps harbored variable numbers of actin binding sites and promoted actin nucleation as determined by in vitro polymerization assays. Our findings indicate that Tarp mediated actin binding and nucleation is a conserved feature among diverse chlamydial species and this function plays a critical role in bacterial invasion of host cells.

Poorer Financial and Health Literacy Among Community-Dwelling Older Adults With Mild Cognitive Impairment.

Science.gov (United States)

Han, S Duke; Boyle, Patricia A; James, Bryan D; Yu, Lei; Bennett, David A

2015-09-01

Literacy is an important determinant of financial and health outcomes in old age, and cognitive decline has been linked with lower literacy. We tested the hypothesis that mild cognitive impairment (MCI) is associated with poorer financial and health literacy. Participants (n = 730) from the Rush Memory and Aging Project were given a clinical evaluation and an assessment of total, financial, and health literacy. Regression was used to examine whether MCI was associated with lower literacy. In secondary analyses, we investigated the association of particular cognitive systems with literacy. MCI was associated with lower total, financial, and health literacy. An interaction was observed such that higher education reduced the effect of MCI on total and financial literacy. Multiple cognitive systems were associated with literacy in participants with MCI, and semantic memory accounted for the most variance. Persons with MCI exhibit poorer financial and health literacy, and education mitigates this effect. © The Author(s) 2015.

Casual Attributions of Adolescent Females in a Masculine Domain.

Science.gov (United States)

Krauser, Barbara Z.; Ballif, Bonnie L.

Achievement attributions of adolescent females in the masculine domain of mathematics were investigated in relation to self-schemas for gender, expectancy of success, and mathematics achievement. The most important findings revealed by multiple regression analysis were that mathematics achievement and the self-schema for masculinity predicted…

Characterization of the molecular basis of group II intron RNA recognition by CRS1-CRM domains.

Science.gov (United States)

Keren, Ido; Klipcan, Liron; Bezawork-Geleta, Ayenachew; Kolton, Max; Shaya, Felix; Ostersetzer-Biran, Oren

2008-08-22

CRM (chloroplast RNA splicing and ribosome maturation) is a recently recognized RNA-binding domain of ancient origin that has been retained in eukaryotic genomes only within the plant lineage. Whereas in bacteria CRM domains exist as single domain proteins involved in ribosome maturation, in plants they are found in a family of proteins that contain between one and four repeats. Several members of this family with multiple CRM domains have been shown to be required for the splicing of specific plastidic group II introns. Detailed biochemical analysis of one of these factors in maize, CRS1, demonstrated its high affinity and specific binding to the single group II intron whose splicing it facilitates, the plastid-encoded atpF intron RNA. Through its association with two intronic regions, CRS1 guides the folding of atpF intron RNA into its predicted "catalytically active" form. To understand how multiple CRM domains cooperate to achieve high affinity sequence-specific binding to RNA, we analyzed the RNA binding affinity and specificity associated with each individual CRM domain in CRS1; whereas CRM3 bound tightly to the RNA, CRM1 associated specifically with a unique region found within atpF intron domain I. CRM2, which demonstrated only low binding affinity, also seems to form specific interactions with regions localized to domains I, III, and IV. We further show that CRM domains share structural similarities and RNA binding characteristics with the well known RNA recognition motif domain.

Frequency-domain method for separating signal and noise

Institute of Scientific and Technical Information of China (English)

无

2000-01-01

A new method for separation of signal and noise (SSN) is put forward. Frequency is redefined according to the features of signal and its derivative in the sampl ing time interval, thus double orthogonal basis (DOB) is constructed so that a signal can be precisely signified with a linear combination of low-frequency DOB . Under joint consideration in time domain (TD) and frequency domain (FD), a method on SSN with high accuracy is derived and a matched algorithm is designed and analyzed. This method is applicable to SSN in multiple frequency bands, and convenient in applying signal characteristics in TD and FD synthetically with highe raccuracy.

Frequency-domain method for separating signal and noise

Institute of Scientific and Technical Information of China (English)

王正明; 段晓君

2000-01-01

A new method for separation of signal and noise (SSN) is put forward. Frequency is redefined according to the features of signal and its derivative in the sampling time interval, thus double orthogonal basis (DOB) is constructed so that a signal can be precisely signified with a linear combination of low-frequency DOB. Under joint consideration in time domain (TD) and frequency domain (FD), a method on SSN with high accuracy is derived and a matched algorithm is designed and analyzed. This method is applicable to SSN in multiple frequency bands, and convenient in applying signal characteristics in TD and FD synthetically with higher accuracy.

A lightning multiple casualty incident in Sequoia and Kings Canyon National Parks.

Science.gov (United States)

Spano, Susanne J; Campagne, Danielle; Stroh, Geoff; Shalit, Marc

2015-03-01

Multiple casualty incidents (MCIs) are uncommon in remote wilderness settings. This is a case report of a lightning strike on a Boy Scout troop hiking through Sequoia and Kings Canyon National Parks (SEKI), in which the lightning storm hindered rescue efforts. The purpose of this study was to review the response to a lightning-caused MCI in a wilderness setting, address lightning injury as it relates to field management, and discuss evacuation options in inclement weather incidents occurring in remote locations. An analysis of SEKI search and rescue data and a review of current literature were performed. A lightning strike at 10,600 feet elevation in the Sierra Nevada Mountains affected a party of 5 adults and 7 Boy Scouts (age range 12 to 17 years old). Resources mobilized for the rescue included 5 helicopters, 2 ambulances, 2 hospitals, and 15 field and 14 logistical support personnel. The incident was managed from strike to scene clearance in 4 hours and 20 minutes. There were 2 fatalities, 1 on scene and 1 in the hospital. Storm conditions complicated on-scene communication and evacuation efforts. Exposure to ongoing lightning and a remote wilderness location affected both victims and rescuers in a lightning MCI. Helicopters, the main vehicles of wilderness rescue in SEKI, can be limited by weather, daylight, and terrain. Redundancies in communication systems are vital for episodes of radio failure. Reverse triage should be implemented in lightning injury MCIs. Education of both wilderness travelers and rescuers regarding these issues should be pursued. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Spectral element method for elastic and acoustic waves in frequency domain

Energy Technology Data Exchange (ETDEWEB)

Shi, Linlin; Zhou, Yuanguo; Wang, Jia-Min; Zhuang, Mingwei [Institute of Electromagnetics and Acoustics, and Department of Electronic Science, Xiamen, 361005 (China); Liu, Na, E-mail: liuna@xmu.edu.cn [Institute of Electromagnetics and Acoustics, and Department of Electronic Science, Xiamen, 361005 (China); Liu, Qing Huo, E-mail: qhliu@duke.edu [Department of Electrical and Computer Engineering, Duke University, Durham, NC, 27708 (United States)

2016-12-15

Numerical techniques in time domain are widespread in seismic and acoustic modeling. In some applications, however, frequency-domain techniques can be advantageous over the time-domain approach when narrow band results are desired, especially if multiple sources can be handled more conveniently in the frequency domain. Moreover, the medium attenuation effects can be more accurately and conveniently modeled in the frequency domain. In this paper, we present a spectral-element method (SEM) in frequency domain to simulate elastic and acoustic waves in anisotropic, heterogeneous, and lossy media. The SEM is based upon the finite-element framework and has exponential convergence because of the use of GLL basis functions. The anisotropic perfectly matched layer is employed to truncate the boundary for unbounded problems. Compared with the conventional finite-element method, the number of unknowns in the SEM is significantly reduced, and higher order accuracy is obtained due to its spectral accuracy. To account for the acoustic-solid interaction, the domain decomposition method (DDM) based upon the discontinuous Galerkin spectral-element method is proposed. Numerical experiments show the proposed method can be an efficient alternative for accurate calculation of elastic and acoustic waves in frequency domain.

General and Domain-Specific Contributions to Creative Ideation and Creative Performance

Directory of Open Access Journals (Sweden)

Donggun An

2016-11-01

Full Text Available The general objective of this study was to reexamine two views of creativity, one positing that there is a general creative capacity or talent and the other that creativity is domain-specific. These two views were compared by (a testing correlations among measures of domain-general and domain-specific creativity and (b examining how the general and the specific measures was each related to indices of knowledge, motivation, and personality. Participants were 147 college students enrolled in a foreign language course. Data were collected on participants’ domain knowledge, motivation, and creative personality, as well as four measures representing “General or Domain-Specific Creative Ideation” or “Creative Performance and Activity”. Results indicated that the four measures of creativity were correlated with one another, except for “General Performance and Activity” and “Domain-Specific Ideation.” A canonical correlation indicated that knowledge, motivation, and personality were significantly correlated with the four creativity measures (Rc = .49, p < .01. Multiple regressions uncovered particular relationships consistent with the view that creativity has both general and domain-specific contributions. Limitations, such as the focus on one domain, and future directions are discussed.

A Switching Anti-windup Design Using Multiple Lyapunov Functions

NARCIS (Netherlands)

Lu, L.; Lin, Z.; Chen, J.

2009-01-01

This paper proposes a switching anti-windup design, which aims to enlarge the domain of attraction of the closed-loop system. Multiple anti-windup gains along with an index function that orchestrates the switching among these anti-windup gains are designed based on the min function of multiple

History, rare, and multiple events of mechanical unfolding of repeat proteins

Science.gov (United States)

Sumbul, Fidan; Marchesi, Arin; Rico, Felix

2018-03-01

Mechanical unfolding of proteins consisting of repeat domains is an excellent tool to obtain large statistics. Force spectroscopy experiments using atomic force microscopy on proteins presenting multiple domains have revealed that unfolding forces depend on the number of folded domains (history) and have reported intermediate states and rare events. However, the common use of unspecific attachment approaches to pull the protein of interest holds important limitations to study unfolding history and may lead to discarding rare and multiple probing events due to the presence of unspecific adhesion and uncertainty on the pulling site. Site-specific methods that have recently emerged minimize this uncertainty and would be excellent tools to probe unfolding history and rare events. However, detailed characterization of these approaches is required to identify their advantages and limitations. Here, we characterize a site-specific binding approach based on the ultrastable complex dockerin/cohesin III revealing its advantages and limitations to assess the unfolding history and to investigate rare and multiple events during the unfolding of repeated domains. We show that this approach is more robust, reproducible, and provides larger statistics than conventional unspecific methods. We show that the method is optimal to reveal the history of unfolding from the very first domain and to detect rare events, while being more limited to assess intermediate states. Finally, we quantify the forces required to unfold two molecules pulled in parallel, difficult when using unspecific approaches. The proposed method represents a step forward toward more reproducible measurements to probe protein unfolding history and opens the door to systematic probing of rare and multiple molecule unfolding mechanisms.

Domains and domain loss

DEFF Research Database (Denmark)

Haberland, Hartmut

2005-01-01

politicians and in the media, especially in the discussion whether some languages undergo ‘domain loss’ vis-à-vis powerful international languages like English. An objection that has been raised here is that domains, as originally conceived, are parameters of language choice and not properties of languages...

Improving the performance of DomainDiscovery of protein domain boundary assignment using inter-domain linker index

Directory of Open Access Journals (Sweden)

Zomaya Albert Y

2006-12-01

Full Text Available Abstract Background Knowledge of protein domain boundaries is critical for the characterisation and understanding of protein function. The ability to identify domains without the knowledge of the structure – by using sequence information only – is an essential step in many types of protein analyses. In this present study, we demonstrate that the performance of DomainDiscovery is improved significantly by including the inter-domain linker index value for domain identification from sequence-based information. Improved DomainDiscovery uses a Support Vector Machine (SVM approach and a unique training dataset built on the principle of consensus among experts in defining domains in protein structure. The SVM was trained using a PSSM (Position Specific Scoring Matrix, secondary structure, solvent accessibility information and inter-domain linker index to detect possible domain boundaries for a target sequence. Results Improved DomainDiscovery is compared with other methods by benchmarking against a structurally non-redundant dataset and also CASP5 targets. Improved DomainDiscovery achieves 70% accuracy for domain boundary identification in multi-domains proteins. Conclusion Improved DomainDiscovery compares favourably to the performance of other methods and excels in the identification of domain boundaries for multi-domain proteins as a result of introducing support vector machine with benchmark_2 dataset.

Identifying College Students' Multiple Intelligences to Enhance Motivation and Language Proficiency

Science.gov (United States)

Madkour, Magda; Mohamed, Rafik Ahmed Abdel Moati

2016-01-01

While most research studies on the theory of multiple intelligences focused on the application of the multiple intelligences domains as separate components, this quasi-experimental research targeted the effect of multiple intelligences as integrated abilities for teaching and learning English at higher education. The purpose of this study was to…

Cognitive and Neural Effects of Vision-Based Speed-of-Processing Training in Older Adults with Amnestic Mild Cognitive Impairment: A Pilot Study.

Science.gov (United States)

Lin, Feng; Heffner, Kathi L; Ren, Ping; Tivarus, Madalina E; Brasch, Judith; Chen, Ding-Geng; Mapstone, Mark; Porsteinsson, Anton P; Tadin, Duje

2016-06-01

To examine the cognitive and neural effects of vision-based speed-of-processing (VSOP) training in older adults with amnestic mild cognitive impairment (aMCI) and contrast those effects with an active control (mental leisure activities (MLA)). Randomized single-blind controlled pilot trial. Academic medical center. Individuals with aMCI (N = 21). Six-week computerized VSOP training. Multiple cognitive processing measures, instrumental activities of daily living (IADLs), and two resting state neural networks regulating cognitive processing: central executive network (CEN) and default mode network (DMN). VSOP training led to significantly greater improvements in trained (processing speed and attention: F1,19  = 6.61, partial η(2)  = 0.26, P = .02) and untrained (working memory: F1,19  = 7.33, partial η(2)  = 0.28, P = .01; IADLs: F1,19  = 5.16, partial η(2)  = 0.21, P = .03) cognitive domains than MLA and protective maintenance in DMN (F1, 9  = 14.63, partial η(2)  = 0.62, P = .004). VSOP training, but not MLA, resulted in a significant improvement in CEN connectivity (Z = -2.37, P = .02). Target and transfer effects of VSOP training were identified, and links between VSOP training and two neural networks associated with aMCI were found. These findings highlight the potential of VSOP training to slow cognitive decline in individuals with aMCI. Further delineation of mechanisms underlying VSOP-induced plasticity is necessary to understand in which populations and under what conditions such training may be most effective. © 2016, Copyright the Authors Journal compilation © 2016, The American Geriatrics Society.

Tsuruga: 1 ton, some 10 mCi of rad-liquid leaks out to the sea, no environmental and human costs

International Nuclear Information System (INIS)

1981-01-01

In the Tsuruga Nuclear Power Station of Japan Atomic Power Co., the leakage of radioactivity from the site into the sea occurred, as follows. Due to a valve being left open on March 8, 1981, the overflow of liquid waste from the filter sludge storage tank into the laundry waste filtering room took place. A part of it leaked through the floor into the general underground waterway. The amount was estimated to be one ton with some 10 mCi. The incident is reviewed with the following topics: nobody expected rad-material in the waterway with the leakage from a filter sludge tank; construction, human and management mistakes were revealed in the survey; no environmental impact, with the defect peculiar to Tsuruga; JAPCO executives assume the responsibility; JAPCO and regulatory authorities need review. (Mori, K.)

Possible description of domain walls in two-dimensional spin glasses by stochastic Loewner evolutions

International Nuclear Information System (INIS)

Bernard, Denis; Le Doussal, Pierre; Middleton, A. Alan

2007-01-01

Domain walls for spin glasses are believed to be scale invariant; a stronger symmetry, conformal invariance, has the potential to hold. The statistics of zero-temperature Ising spin glass domain walls in two dimensions are used to test the hypothesis that these domain walls are described by a Schramm-Loewner evolution SLE κ . Multiple tests are consistent with SLE κ , where κ=2.32±0.08. Both conformal invariance and the domain Markov property are tested. The latter does not hold in small systems, but detailed numerical evidence suggests that it holds in the continuum limit

Strategy-Proof Assignment Of Multiple Resources

DEFF Research Database (Denmark)

Erlanson, Albin; Szwagrzak, Karol

2015-01-01

We examine the strategy-proof allocation of multiple resources; an application is the assignment of packages of tasks, workloads, and compensations among the members of an organization. In the domain of multidimensional single-peaked preferences, we find that any allocation mechanism obtained by ...

RNA-protein binding motifs mining with a new hybrid deep learning based cross-domain knowledge integration approach

DEFF Research Database (Denmark)

Pan, Xiaoyong; Shen, Hong Bin

2017-01-01

, their domain specific features and formats have posed significant computational challenges. One of current difficulties is that the cross-source shared common knowledge is at a higher abstraction level beyond the observed data, resulting in a low efficiency of direct integration of observed data across domains...... space using multiple layers of learning blocks, where the shared representations across different domains are integrated. To validate our iDeep method, we performed experiments on 31 large-scale CLIP-seq datasets, and our results show that by integrating multiple sources of data, the average AUC can...... be improved by 8% compared to the best single-source-based predictor; and through cross-domain knowledge integration at an abstraction level, it outperforms the state-of-the-art predictors by 6%. Besides the overall enhanced prediction performance, the convolutional neural network module embedded in i...

Principles of Eliminating Access Control Lists within a Domain

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Vic Grout

2012-04-01

Full Text Available The infrastructure of large networks is broken down into areas that have a common security policy called a domain. Security within a domain is commonly implemented at all nodes. However this can have a negative effect on performance since it introduces a delay associated with packet filtering. When Access Control Lists (ACLs are used within a router for this purpose then a significant overhead is introduced associated with this process. It is likely that identical checks are made at multiple points within a domain prior to a packet reaching its destination. Therefore by eliminating ACLs within a domain by modifying the ingress/egress points with equivalent functionality an improvement in the overall performance can be obtained. This paper considers the effect of the delays when using router operating systems offering different levels of functionality. It considers factors which contribute to the delay particularly due to ACLs and by using theoretical principles modified by practical calculation a model is created. Additionally this paper provides an example of an optimized solution which reduces the delay through network routers by distributing the security rules to the ingress/egress points of the domain without affecting the security policy.

WW domain folding complexity revealed by infrared spectroscopy.

Science.gov (United States)

Davis, Caitlin M; Dyer, R Brian

2014-09-02

Although the intrinsic tryptophan fluorescence of proteins offers a convenient probe of protein folding, interpretation of the fluorescence spectrum is often difficult because it is sensitive to both global and local changes. Infrared (IR) spectroscopy offers a complementary measure of structural changes involved in protein folding, because it probes changes in the secondary structure of the protein backbone. Here we demonstrate the advantages of using multiple probes, infrared and fluorescence spectroscopy, to study the folding of the FBP28 WW domain. Laser-induced temperature jumps coupled with fluorescence or infrared spectroscopy have been used to probe changes in the peptide backbone on the submillisecond time scale. The relaxation dynamics of the β-sheets and β-turn were measured independently by probing the corresponding IR bands assigned in the amide I region. Using these wavelength-dependent measurements, we observe three kinetics phases, with the fastest process corresponding to the relaxation kinetics of the turns. In contrast, fluorescence measurements of the wild-type WW domain and tryptophan mutants exhibit single-exponential kinetics with a lifetime that corresponds to the slowest phase observed by infrared spectroscopy. Mutant sequences provide evidence of an intermediate dry molten globule state. The slowest step in the folding of this WW domain is the tight packing of the side chains in the transition from the dry molten globule intermediate to the native structure. This study demonstrates that using multiple complementary probes enhances the interpretation of protein folding dynamics.

Association between fully automated MRI-based volumetry of different brain regions and neuropsychological test performance in patients with amnestic mild cognitive impairment and Alzheimer's disease.

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Arlt, Sönke; Buchert, Ralph; Spies, Lothar; Eichenlaub, Martin; Lehmbeck, Jan T; Jahn, Holger

2013-06-01

Fully automated magnetic resonance imaging (MRI)-based volumetry may serve as biomarker for the diagnosis in patients with mild cognitive impairment (MCI) or dementia. We aimed at investigating the relation between fully automated MRI-based volumetric measures and neuropsychological test performance in amnestic MCI and patients with mild dementia due to Alzheimer's disease (AD) in a cross-sectional and longitudinal study. In order to assess a possible prognostic value of fully automated MRI-based volumetry for future cognitive performance, the rate of change of neuropsychological test performance over time was also tested for its correlation with fully automated MRI-based volumetry at baseline. In 50 subjects, 18 with amnestic MCI, 21 with mild AD, and 11 controls, neuropsychological testing and T1-weighted MRI were performed at baseline and at a mean follow-up interval of 2.1 ± 0.5 years (n = 19). Fully automated MRI volumetry of the grey matter volume (GMV) was performed using a combined stereotactic normalisation and segmentation approach as provided by SPM8 and a set of pre-defined binary lobe masks. Left and right hippocampus masks were derived from probabilistic cytoarchitectonic maps. Volumes of the inner and outer liquor space were also determined automatically from the MRI. Pearson's test was used for the correlation analyses. Left hippocampal GMV was significantly correlated with performance in memory tasks, and left temporal GMV was related to performance in language tasks. Bilateral frontal, parietal and occipital GMVs were correlated to performance in neuropsychological tests comprising multiple domains. Rate of GMV change in the left hippocampus was correlated with decline of performance in the Boston Naming Test (BNT), Mini-Mental Status Examination, and trail making test B (TMT-B). The decrease of BNT and TMT-A performance over time correlated with the loss of grey matter in multiple brain regions. We conclude that fully automated MRI

Memory deficits for facial identity in patients with amnestic mild cognitive impairment (MCI).

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Savaskan, Egemen; Summermatter, Daniel; Schroeder, Clemens; Schächinger, Hartmut

2018-01-01

Faces are among the most relevant social stimuli revealing an encounter's identity and actual emotional state. Deficits in facial recognition may be an early sign of cognitive decline leading to social deficits. The main objective of the present study is to investigate if individuals with amnestic mild cognitive impairment show recognition deficits in facial identity. Thirty-seven individuals with amnestic mild cognitive impairment, multiple-domain (15 female; age: 75±8 yrs.) and forty-one healthy volunteers (24 female; age 71±6 yrs.) participated. All participants completed a human portrait memory test presenting unfamiliar faces with happy and angry emotional expressions. Five and thirty minutes later, old and new neutral faces were presented, and discrimination sensitivity (d') and response bias (C) were assessed as signal detection parameters of cued facial identity recognition. Memory performance was lower in amnestic mild cognitive impairment as compared to control subjects, mainly because of an altered response bias towards an increased false alarm rate (favoring false OLD ascription of NEW items). In both groups, memory performance declined between the early and later testing session, and was always better for acquired happy than angry faces. Facial identity memory is impaired in patients with amnestic mild cognitive impairment. Liberalization of the response bias may reflect a socially motivated compensatory mechanism maintaining an almost identical recognition hit rate of OLD faces in individuals with amnestic mild cognitive impairment.

Predictive value of different conventional and non-conventional MRI-parameters for specific domains of cognitive function in multiple sclerosis.

Science.gov (United States)

Pinter, Daniela; Khalil, Michael; Pichler, Alexander; Langkammer, Christian; Ropele, Stefan; Marschik, Peter B; Fuchs, Siegrid; Fazekas, Franz; Enzinger, Christian

2015-01-01

While many studies correlated cognitive function with changes in brain morphology in multiple sclerosis (MS), few of them used a multi-parametric approach in a single dataset so far. We thus here assessed the predictive value of different conventional and quantitative MRI-parameters both for overall and domain-specific cognitive performance in MS patients from a single center. 69 patients (17 clinically isolated syndrome, 47 relapsing-remitting MS, 5 secondary-progressive MS) underwent the "Brief Repeatable Battery of Neuropsychological Tests" assessing overall cognition, cognitive efficiency and memory function as well as MRI at 3 Tesla to obtain T2-lesion load (T2-LL), normalized brain volume (global brain volume loss), normalized cortical volume (NCV), normalized thalamic volume (NTV), normalized hippocampal volume (NHV), normalized caudate nuclei volume (NCNV), basal ganglia R2* values (iron deposition) and magnetization transfer ratios (MTRs) for cortex and normal appearing brain tissue (NABT). Regression models including clinical, demographic variables and MRI-parameters explained 22-27% of variance of overall cognition, 17-26% of cognitive efficiency and 22-23% of memory. NCV, T2-LL and MTR of NABT were the strongest predictors of overall cognitive function. Cognitive efficiency was best predicted by NCV, T2-LL and iron deposition in the basal ganglia. NTV was the strongest predictor for memory function and NHV was particularly related to memory function. The predictive value of distinct MRI-parameters differs for specific domains of cognitive function, with a greater impact of cortical volume, focal and diffuse white matter abnormalities on overall cognitive function, an additional role of basal ganglia iron deposition on cognitive efficiency, and thalamic and hippocampal volume on memory function. This suggests the usefulness of using multiparametric MRI to assess (micro)structural correlates of different cognitive constructs.

PEMBUATAN SUMBER RADIASI GAMMA 137Cs DENGAN AKTIVITAS 20 mCi DARI PEB U3Si2-Al PASCA IRADIASI DALAM CONTAINER STAINLESS STEEL

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Aslina Br. Ginting

2016-03-01

Full Text Available ABSTRAK PEMBUATAN SUMBER RADIASI GAMMA ISOTOP 137Cs DENGAN AKTIVITAS 20 mCi DARI PEB U3Si2-Al PASCA IRADIASI DALAM CONTAINER STAINLESS STEEL. Kegiatan uji pasca iradiasi pelat elemen bakar (PEB U3Si2-Al banyak menghasilkan larutan dengan keaktifan yang sangat tinggi. Larutan tersebut mengandung isotop 137Cs, uranium serta transuranium yang mempunyai waktu paroh panjang dan berbahaya bagi lingkungan. Namun larutan tersebut memiliki nilai ekonomis tinggi karena dapat dimanfaatkan sebagai bahan baku untuk pembuatan sumber radiasi sinar gamma isotop 137Cs. Hal ini dapat membantu bidang industri dalam memenuhi kebutuhan sumber radioaktif dalam negeri karena selama ini kebutuhan isotop 137Cs di Indonesia masih tergantung dari industri luar negeri. Selain itu, pengadaan dan transportasi isotop 137Cs dari luar negeri serta dalam penggunaannya memerlukan persyaratan yang cukup ketat dari Badan Pengawas Tenaga Nuklir Nasional (BAPETEN, sehingga menyebabkan harga isotop 137Cs menjadi mahal sampai di Indonesia. Dengan alasan tersebut, BATAN sebagai lembaga litbang nuklir di Indonesia perlu mempelajari pembuatan sumber radiasi gamma isotop 137Cs dari larutan hasil pengujian bahan bakar nuklir U3Si2-Al pasca iradiasi. Manfaat isotop 137Cs sangat luas antara lain digunakan dalam menganalisis sampel lingkungan, industri migas, konstruksi, radiografi, perikanan, rumah sakit dan pertambangan. Pembuatan sumber radiasi gamma isotop 137Cs dimulai dari pengumpulan larutan hasil pengujian PEB U3Si2-Al. Larutan larutan hasil pengujian mengandung isotop 137Cs dan isotop lainnya dikumpulkan menjadi satu dalam botol dengan volume 65 mL. Pemisahan isotop 137Cs dari hasil fisi lainnya dilakukan dengan metode penukar kation menggunakan zeolit Lampung dengan berat 45 gr. Hasil pemisahan diperoleh 137Cs-zeolit dalam fasa padat dan isotop lainnya berada dalam fasa cair. Padatan137Cs-zeolit kering kemudian kemudian ditimbang dan diukur aktivitasnya menggunakan spektrometer

Three dimensional image reconstruction in the Fourier domain

International Nuclear Information System (INIS)

Stearns, C.W.; Chesler, D.A.; Brownell, G.L.

1987-01-01

Filtered backprojection reconstruction algorithms are based upon the relationship between the Fourier transform of the imaged object and the Fourier transforms of its projections. A new reconstruction algorithm has been developed which performs the image assembly operation in Fourier space, rather than in image space by backprojection. This represents a significant decrease in the number of operations required to assemble the image. The new Fourier domain algorithm has resolution comparable to the filtered backprojection algorithm, and, after correction by a pointwise multiplication, demonstrates proper recovery throughout image space. Although originally intended for three-dimensional imaging applications, the Fourier domain algorithm can also be developed for two-dimensional imaging applications such as planar positron imaging systems

Disconnection as a Mechanism for Cognitive Dysfunction in Multiple Sclerosis

Science.gov (United States)

Dineen, R. A.; Vilisaar, J.; Hlinka, J.; Bradshaw, C. M.; Morgan, P. S.; Constantinescu, C. S.; Auer, D. P.

2009-01-01

Disconnection of cognitively important processing regions by injury to the interconnecting white matter provides a potential mechanism for cognitive dysfunction in multiple sclerosis. The contribution of tract-specific white matter injury to dysfunction in different cognitive domains in patients with multiple sclerosis has not previously been…

Writing Impairments in Japanese Patients with Mild Cognitive Impairment and with Mild Alzheimer's Disease.

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Hayashi, Atsuko; Nomura, Hiroshi; Mochizuki, Ruriko; Ohnuma, Ayumu; Kimpara, Teiko; Suzuki, Kyoko; Mori, Etsuro

2015-01-01

We investigated writing abilities in patients with the amnestic type of mild cognitive impairment (aMCI) and mild Alzheimer's disease (AD). To examine the earliest changes in writing function, we used writing tests for both words and sentences with different types of Japanese characters (Hiragana, Katakana, and Kanji). A total of 25 aMCI patients, 38 AD patients, and 22 healthy controls performed writing to dictation for Kana and Kanji words, copied Kanji words, and wrote in response to a picture story task. Analysis of variance was used to test the subject group effects on the scores in the above writing tasks. For the written Kanji words, the mild AD group performed worse than the aMCI group and the controls, but there was no difference between the aMCI group and the controls. For the picture story writing task, the mild AD and aMCI groups performed worse than the controls, but the difference between the AD and the aMCI groups was not significant. The mild AD group showed defects in writing Kanji characters, and the aMCI group showed impairments in narrative writing. Our study suggests that narrative writing, which demands complex integration of multiple cognitive functions, can be used to detect the subtle writing deficits in aMCI patients.

Structure of PIN-domain protein PH0500 from Pyrococcus horikoshii

International Nuclear Information System (INIS)

Jeyakanthan, Jeyaraman; Inagaki, Eiji; Kuroishi, Chizu; Tahirov, Tahir H.

2005-01-01

The structure of P. horikoshii OT3 protein PH0500 was determined by the multiple anomalous dispersion method and refined in two crystal forms. The protein is a dimer and has a PIN-domain fold. The Pyrococcus horikoshii OT3 protein PH0500 is highly conserved within the Pyrococcus genus of hyperthermophilic archaea and shows low amino-acid sequence similarity with a family of PIN-domain proteins. The protein has been expressed, purified and crystallized in two crystal forms: PH0500-I and PH0500-II. The structure was determined at 2.0 Å by the multiple anomalous dispersion method using a selenomethionyl derivative of crystal form PH0500-I (PH0500-I-Se). The structure of PH0500-I has been refined at 1.75 Å resolution to an R factor of 20.9% and the structure of PH0500-II has been refined at 2.0 Å resolution to an R factor of 23.4%. In both crystal forms as well as in solution the molecule appears to be a dimer. Searches of the databases for protein-fold similarities confirmed that the PH0500 protein is a PIN-domain protein with possible exonuclease activity and involvement in DNA or RNA editing

Comparison of Multiple-Microphone and Single-Loudspeaker Adaptive Feedback/Echo Cancellation Systems

DEFF Research Database (Denmark)

Guo, Meng; Elmedyb, Thomas Bo; Jensen, Søren Holdt

2011-01-01

Recently, we introduced a frequency domain measure - the power transfer function - to predict the convergence rate, system stability bound and the steady-state behavior across time and frequency of a least mean square based feedback/echo cancellation algorithm in a general multiple-microphone and......Recently, we introduced a frequency domain measure - the power transfer function - to predict the convergence rate, system stability bound and the steady-state behavior across time and frequency of a least mean square based feedback/echo cancellation algorithm in a general multiple...

Domain configurations in dislocations embedded hexagonal manganite systems: From the view of graph theory

Science.gov (United States)

Cheng, Shaobo; Zhang, Dong; Deng, Shiqing; Li, Xing; Li, Jun; Tan, Guotai; Zhu, Yimei; Zhu, Jing

2018-04-01

Topological defects and their interactions often arouse multiple types of emerging phenomena from edge states in Skyrmions to disclination pairs in liquid crystals. In hexagonal manganites, partial edge dislocations, a prototype topological defect, are ubiquitous and they significantly alter the topologically protected domains and their behaviors. Herein, combining electron microscopy experiment and graph theory analysis, we report a systematic study of the connections and configurations of domains in this dislocation embedded system. Rules for domain arrangement are established. The dividing line between domains, which can be attributed by the strain field of dislocations, is accurately described by a genus model from a higher dimension in the graph theory. Our results open a door for the understanding of domain patterns in topologically protected multiferroic systems.

Correlation of MRI Visual Scales with Neuropsychological Profile in Mild Cognitive Impairment of Parkinson’s Disease

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Luiz Felipe Vasconcellos

2017-01-01

Full Text Available Few studies have evaluated magnetic resonance imaging (MRI visual scales in Parkinson’s disease-Mild Cognitive Impairment (PD-MCI. We selected 79 PD patients and 92 controls (CO to perform neurologic and neuropsychological evaluation. Brain MRI was performed to evaluate the following scales: Global Cortical Atrophy (GCA, Fazekas, and medial temporal atrophy (MTA. The analysis revealed that both PD groups (amnestic and nonamnestic showed worse performance on several tests when compared to CO. Memory, executive function, and attention impairment were more severe in amnestic PD-MCI group. Overall analysis of frequency of MRI visual scales by MCI subtype did not reveal any statistically significant result. Statistically significant inverse correlation was observed between GCA scale and Mini-Mental Status Examination (MMSE, Montreal Cognitive Assessment (MoCA, semantic verbal fluency, Stroop test, figure memory test, trail making test (TMT B, and Rey Auditory Verbal Learning Test (RAVLT. The MTA scale correlated with Stroop test and Fazekas scale with figure memory test, digit span, and Stroop test according to the subgroup evaluated. Visual scales by MRI in MCI should be evaluated by cognitive domain and might be more useful in more severely impaired MCI or dementia patients.

Drosophila Pumilio protein contains multiple autonomous repression domains that regulate mRNAs independently of Nanos and brain tumor.

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Weidmann, Chase A; Goldstrohm, Aaron C

2012-01-01

Drosophila melanogaster Pumilio is an RNA-binding protein that potently represses specific mRNAs. In developing embryos, Pumilio regulates a key morphogen, Hunchback, in collaboration with the cofactor Nanos. To investigate repression by Pumilio and Nanos, we created cell-based assays and found that Pumilio inhibits translation and enhances mRNA decay independent of Nanos. Nanos robustly stimulates repression through interactions with the Pumilio RNA-binding domain. We programmed Pumilio to recognize a new binding site, which garners repression of new target mRNAs. We show that cofactors Brain Tumor and eIF4E Homologous Protein are not obligatory for Pumilio and Nanos activity. The conserved RNA-binding domain of Pumilio was thought to be sufficient for its function. Instead, we demonstrate that three unique domains in the N terminus of Pumilio possess the major repressive activity and can function autonomously. The N termini of insect and vertebrate Pumilio and Fem-3 binding factors (PUFs) are related, and we show that corresponding regions of human PUM1 and PUM2 have repressive activity. Other PUF proteins lack these repression domains. Our findings suggest that PUF proteins have evolved new regulatory functions through protein sequences appended to their conserved PUF repeat RNA-binding domains.

Improvement in Protein Domain Identification Is Reached by Breaking Consensus, with the Agreement of Many Profiles and Domain Co-occurrence.

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Juliana Bernardes

2016-07-01

Full Text Available Traditional protein annotation methods describe known domains with probabilistic models representing consensus among homologous domain sequences. However, when relevant signals become too weak to be identified by a global consensus, attempts for annotation fail. Here we address the fundamental question of domain identification for highly divergent proteins. By using high performance computing, we demonstrate that the limits of state-of-the-art annotation methods can be bypassed. We design a new strategy based on the observation that many structural and functional protein constraints are not globally conserved through all species but might be locally conserved in separate clades. We propose a novel exploitation of the large amount of data available: 1. for each known protein domain, several probabilistic clade-centered models are constructed from a large and differentiated panel of homologous sequences, 2. a decision-making protocol combines outcomes obtained from multiple models, 3. a multi-criteria optimization algorithm finds the most likely protein architecture. The method is evaluated for domain and architecture prediction over several datasets and statistical testing hypotheses. Its performance is compared against HMMScan and HHblits, two widely used search methods based on sequence-profile and profile-profile comparison. Due to their closeness to actual protein sequences, clade-centered models are shown to be more specific and functionally predictive than the broadly used consensus models. Based on them, we improved annotation of Plasmodium falciparum protein sequences on a scale not previously possible. We successfully predict at least one domain for 72% of P. falciparum proteins against 63% achieved previously, corresponding to 30% of improvement over the total number of Pfam domain predictions on the whole genome. The method is applicable to any genome and opens new avenues to tackle evolutionary questions such as the reconstruction of

ATP binding to p97/VCP D1 domain regulates selective recruitment of adaptors to its proximal N-domain.

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Wei Sheng Chia

Full Text Available p97/Valosin-containing protein (VCP is a member of the AAA-ATPase family involved in many cellular processes including cell division, intracellular trafficking and extraction of misfolded proteins in endoplasmic reticulum-associated degradation (ERAD. It is a homohexamer with each subunit containing two tandem D1 and D2 ATPase domains and N- and C-terminal regions that function as adaptor protein binding domains. p97/VCP is directed to its many different functional pathways by associating with various adaptor proteins. The regulation of the recruitment of the adaptor proteins remains unclear. Two adaptor proteins, Ufd1/Npl4 and p47, which bind exclusively to the p97/VCP N-domain and direct p97/VCP to either ERAD-related processes or homotypic fusion of Golgi fragments, were studied here. Surface plasmon resonance biosensor-based assays allowed the study of binding kinetics in real time. In competition experiments, it was observed that in the presence of ATP, Ufd1/Npl4 was able to compete more effectively with p47 for binding to p97/VCP. By using non-hydrolysable ATP analogues and the hexameric truncated p97/N-D1 fragment, it was shown that binding rather than hydrolysis of ATP to the proximal D1 domain strengthened the Ufd1/Npl4 association with the N-domain, thus regulating the recruitment of either Ufd1/Npl4 or p47. This novel role of ATP and an assigned function to the D1 AAA-ATPase domain link the multiple functions of p97/VCP to the metabolic status of the cell.

ATP binding to p97/VCP D1 domain regulates selective recruitment of adaptors to its proximal N-domain.

Science.gov (United States)

Chia, Wei Sheng; Chia, Diana Xueqi; Rao, Feng; Bar Nun, Shoshana; Geifman Shochat, Susana

2012-01-01

p97/Valosin-containing protein (VCP) is a member of the AAA-ATPase family involved in many cellular processes including cell division, intracellular trafficking and extraction of misfolded proteins in endoplasmic reticulum-associated degradation (ERAD). It is a homohexamer with each subunit containing two tandem D1 and D2 ATPase domains and N- and C-terminal regions that function as adaptor protein binding domains. p97/VCP is directed to its many different functional pathways by associating with various adaptor proteins. The regulation of the recruitment of the adaptor proteins remains unclear. Two adaptor proteins, Ufd1/Npl4 and p47, which bind exclusively to the p97/VCP N-domain and direct p97/VCP to either ERAD-related processes or homotypic fusion of Golgi fragments, were studied here. Surface plasmon resonance biosensor-based assays allowed the study of binding kinetics in real time. In competition experiments, it was observed that in the presence of ATP, Ufd1/Npl4 was able to compete more effectively with p47 for binding to p97/VCP. By using non-hydrolysable ATP analogues and the hexameric truncated p97/N-D1 fragment, it was shown that binding rather than hydrolysis of ATP to the proximal D1 domain strengthened the Ufd1/Npl4 association with the N-domain, thus regulating the recruitment of either Ufd1/Npl4 or p47. This novel role of ATP and an assigned function to the D1 AAA-ATPase domain link the multiple functions of p97/VCP to the metabolic status of the cell.

Activator Gcn4 employs multiple segments of Med15/Gal11, including the KIX domain, to recruit mediator to target genes in vivo.

Science.gov (United States)

Jedidi, Iness; Zhang, Fan; Qiu, Hongfang; Stahl, Stephen J; Palmer, Ira; Kaufman, Joshua D; Nadaud, Philippe S; Mukherjee, Sujoy; Wingfield, Paul T; Jaroniec, Christopher P; Hinnebusch, Alan G

2010-01-22

Mediator is a multisubunit coactivator required for initiation by RNA polymerase II. The Mediator tail subdomain, containing Med15/Gal11, is a target of the activator Gcn4 in vivo, critical for recruitment of native Mediator or the Mediator tail subdomain present in sin4Delta cells. Although several Gal11 segments were previously shown to bind Gcn4 in vitro, the importance of these interactions for recruitment of Mediator and transcriptional activation by Gcn4 in cells was unknown. We show that interaction of Gcn4 with the Mediator tail in vitro and recruitment of this subcomplex and intact Mediator to the ARG1 promoter in vivo involve additive contributions from three different segments in the N terminus of Gal11. These include the KIX domain, which is a critical target of other activators, and a region that shares a conserved motif (B-box) with mammalian coactivator SRC-1, and we establish that B-box is a critical determinant of Mediator recruitment by Gcn4. We further demonstrate that Gcn4 binds to the Gal11 KIX domain directly and, by NMR chemical shift analysis combined with mutational studies, we identify the likely binding site for Gcn4 on the KIX surface. Gcn4 is distinctive in relying on comparable contributions from multiple segments of Gal11 for efficient recruitment of Mediator in vivo.

Time-Domain Diversity in Ultra-Wideband MIMO Communications

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Alain Sibille

2005-03-01

Full Text Available The development of ultra-wideband (UWB communications is impeded by the drastic transmitted power limitations imposed by regulation authorities due to the “polluting” character of these radio emissions with respect to existing services. Technical solutions must be researched in order either to limit the level of spectral pollution by UWB devices or to increase their reception sensitivity. In the present work, we consider pulse-based modulations and investigate time-domain multiple-input multiple-output (MIMO diversity as one such possible solution. The basic principles of time-domain diversity in the extreme (low multipath density or intermediate (dense multipath UWB regimes are addressed, which predict the possibility of a MIMO gain equal to the product Nt×Nr of the numbers of transmit/receive antenna elements when the channel is not too severe. This analysis is confirmed by simulations using a parametric empirical stochastic double-directional channel model. They confirm the potential interest of MIMO approaches solutions in order to bring a valuable performance gain in UWB communications.

Glucose uptake heterogeneity of the leg muscles is similar between patients with multiple sclerosis and healthy controls during walking.

Science.gov (United States)

Kindred, John H; Ketelhut, Nathaniel B; Rudroff, Thorsten

2015-02-01

Difficulties in ambulation are one of the main problems reported by patients with multiple sclerosis. A previous study by our research group showed increased recruitment of muscle groups during walking, but the influence of skeletal muscle properties, such as muscle fiber activity, has not been fully elucidated. The purpose of this investigation was to use the novel method of calculating glucose uptake heterogeneity in the leg muscles of patients with multiple sclerosis and compare these results to healthy controls. Eight patients with multiple sclerosis (4 men) and 8 healthy controls (4 men) performed 15 min of treadmill walking at a comfortable self-selected speed following muscle strength tests. Participants were injected with ≈ 8 mCi of [(18)F]-fluorodeoxyglucose during walking after which positron emission tomography/computed tomography imaging was performed. No differences in muscle strength were detected between multiple sclerosis and control groups (P>0.27). Within the multiple sclerosis, group differences in muscle volume existed between the stronger and weaker legs in the vastus lateralis, semitendinosus, and semimembranosus (Pmuscle group or individual muscle of the legs (P>0.16, P≥0.05). Patients with multiple sclerosis and healthy controls showed similar muscle fiber activity during walking. Interpretations of these results, with respect to our previous study, suggest that walking difficulties in patients with multiple sclerosis may be more associated with altered central nervous system motor patterns rather than alterations in skeletal muscle properties. Published by Elsevier Ltd.

Massive parallelization of a 3D finite difference electromagnetic forward solution using domain decomposition methods on multiple CUDA enabled GPUs

Science.gov (United States)

Schultz, A.

2010-12-01

3D forward solvers lie at the core of inverse formulations used to image the variation of electrical conductivity within the Earth's interior. This property is associated with variations in temperature, composition, phase, presence of volatiles, and in specific settings, the presence of groundwater, geothermal resources, oil/gas or minerals. The high cost of 3D solutions has been a stumbling block to wider adoption of 3D methods. Parallel algorithms for modeling frequency domain 3D EM problems have not achieved wide scale adoption, with emphasis on fairly coarse grained parallelism using MPI and similar approaches. The communications bandwidth as well as the latency required to send and receive network communication packets is a limiting factor in implementing fine grained parallel strategies, inhibiting wide adoption of these algorithms. Leading Graphics Processor Unit (GPU) companies now produce GPUs with hundreds of GPU processor cores per die. The footprint, in silicon, of the GPU's restricted instruction set is much smaller than the general purpose instruction set required of a CPU. Consequently, the density of processor cores on a GPU can be much greater than on a CPU. GPUs also have local memory, registers and high speed communication with host CPUs, usually through PCIe type interconnects. The extremely low cost and high computational power of GPUs provides the EM geophysics community with an opportunity to achieve fine grained (i.e. massive) parallelization of codes on low cost hardware. The current generation of GPUs (e.g. NVidia Fermi) provides 3 billion transistors per chip die, with nearly 500 processor cores and up to 6 GB of fast (DDR5) GPU memory. This latest generation of GPU supports fast hardware double precision (64 bit) floating point operations of the type required for frequency domain EM forward solutions. Each Fermi GPU board can sustain nearly 1 TFLOP in double precision, and multiple boards can be installed in the host computer system. We

Reliability and Validity of the Clinical Dementia Rating for Community-Living Elderly Subjects without an Informant.

Science.gov (United States)

Nyunt, Ma Shwe Zin; Chong, Mei Sian; Lim, Wee Shiong; Lee, Tih Shih; Yap, Philip; Ng, Tze Pin

2013-01-01

The Clinical Dementia Rating (CDR) scale is widely used to assess cognitive impairment in Alzheimer's disease. It requires collateral information from a reliable informant who is not available in many instances. We adapted the original CDR scale for use with elderly subjects without an informant (CDR-NI) and evaluated its reliability and validity for assessing mild cognitive impairment (MCI) and dementia among community-dwelling elderly subjects. At two consecutive visits 1 week apart, nurses trained in CDR assessment interviewed, observed and rated cognitive and functional performance according to a protocol in 90 elderly subjects with suboptimal cognitive performance [Mini-Mental State Examination (MMSE) reliability (κ 0.77-1.00 for six domains and 0.95 for global rating) and test-retest reliability (κ 0.75-1.00 for six domains and 0.80 for global rating), good agreement (κ 0.79) with the clinical assessment status of MCI (n = 37) and dementia (n = 4) and significant differences in the mean scores for MMSE, MOCA and Instrumental Activities of Daily Living (ANOVA global p reliable assessment of MCI and dementia in community-living elderly subjects without an informant.

Doctor, Should I Use Computer Games to Prevent Dementia?

Science.gov (United States)

O'Shea, Deirdre M; De Wit, Liselotte; Smith, Glenn E

2017-08-23

Commercial advertising of computerized "brain games" may result in clinicians being asked whether brain games prevent dementia. To address this question, we conducted a review of computerized cognitive training (CCT) interventions in older adults with Mild Cognitive Impairment (MCI). Studies were identified using a PubMed and PSYCinfo search for review articles. Within 11 review articles we identified 15 unique studies. Nine of these studies used commercially available "brain games" as their primary CCT intervention. Nine of 12 studies that examined the effect of CCT on episodic memory performance showed significant improvements in this domain. Furthermore, four of six studies that examined mood and or anxiety showed improvements in these domains following a CCT intervention. While more than double the amount of time was spent on the training that used commercially available "brain games" versus those designed by investigators, there were no differences in outcomes. Overall, it appears that "brain games" may modestly benefit aspects of cognition and aspects of mood in patients presenting with MCI. However, there is no direct evidence from the studies presented here that "brain games"/CCT can prevent dementia. We present recommendations to consider when discussing "brain games" with persons with MCI.

Segregated nodal domains of two-dimensional multispecies Bose-Einstein condensates

Science.gov (United States)

Chang, Shu-Ming; Lin, Chang-Shou; Lin, Tai-Chia; Lin, Wen-Wei

2004-09-01

In this paper, we study the distribution of m segregated nodal domains of the m-mixture of Bose-Einstein condensates under positive and large repulsive scattering lengths. It is shown that components of positive bound states may repel each other and form segregated nodal domains as the repulsive scattering lengths go to infinity. Efficient numerical schemes are created to confirm our theoretical results and discover a new phenomenon called verticillate multiplying, i.e., the generation of multiple verticillate structures. In addition, our proposed Gauss-Seidel-type iteration method is very effective in that it converges linearly in 10-20 steps.

WESSELÉNYI DOMAIN OF JIBOU, A MODEL OF MULTISECULAR ARRANGEMENT

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ROZALIA BENEDEK

2015-10-01

Full Text Available Wesselényi Domain of Jibou, a Model of Multisecular Arrangement. Nowadays the nobiliary domains arouse the interest of specialists from various field and tourists. The typical nobility constructions are attractive both by their residential function –including curias, castles and palaces in Transylvania – and by the economic function of annexes composed of: mills, barns, stables, riding houses etc. These domains functioned as command centres of territorial arrangements from Medieval Age, premodern and modern ages with implications on the economic and social progress of ages and administrative structures, but also subsequent development. Our study aims to make a presentation of the nobiliary domain Wesselényi in Jibou, aiming to the identification of functions and strategic arrangements for valorisation of the domain as irradiation models of welfare and multiple values, which became a multisecular standard by: emblematic characters, decisive actions carried out by these characters, in Transylvania, Hungary and the Habsburg Empire, to which the Principality of Transylvania belonged until the Great Union of 1918. The management of Jibou domain of Wesselényi family was carried out by various state institutions after the nationalization of 1945, stipulated by Law 187/1945, occasion of new arrangement and valorisation strategies which will also be presented.

Multiple functional roles of the accessory I-domain of bacteriophage P22 coat protein revealed by NMR structure and CryoEM modeling.

Science.gov (United States)

Rizzo, Alessandro A; Suhanovsky, Margaret M; Baker, Matthew L; Fraser, LaTasha C R; Jones, Lisa M; Rempel, Don L; Gross, Michael L; Chiu, Wah; Alexandrescu, Andrei T; Teschke, Carolyn M

2014-06-10

Some capsid proteins built on the ubiquitous HK97-fold have accessory domains imparting specific functions. Bacteriophage P22 coat protein has a unique insertion domain (I-domain). Two prior I-domain models from subnanometer cryoelectron microscopy (cryoEM) reconstructions differed substantially. Therefore, the I-domain's nuclear magnetic resonance structure was determined and also used to improve cryoEM models of coat protein. The I-domain has an antiparallel six-stranded β-barrel fold, not previously observed in HK97-fold accessory domains. The D-loop, which is dynamic in the isolated I-domain and intact monomeric coat protein, forms stabilizing salt bridges between adjacent capsomers in procapsids. The S-loop is important for capsid size determination, likely through intrasubunit interactions. Ten of 18 coat protein temperature-sensitive-folding substitutions are in the I-domain, indicating its importance in folding and stability. Several are found on a positively charged face of the β-barrel that anchors the I-domain to a negatively charged surface of the coat protein HK97-core. Copyright © 2014 Elsevier Ltd. All rights reserved.

Probing the Free Energy Landscape of the FBP28 WW Domain Using Multiple Techniques

NARCIS (Netherlands)

Periole, Xavier; Allen, Lucy R.; Tamiola, Kamil; Mark, Alan E.; Paci, Emanuele

The free-energy landscape of a small protein, the FBP 28 WW domain, has been explored using molecular dynamics (MD) simulations with alternative descriptions of the molecule. The molecular models used range from coarse-grained to all-atom with either an implicit or explicit treatment of the solvent.

Hybrid approaches for multiple-species stochastic reaction-diffusion models

Science.gov (United States)

Spill, Fabian; Guerrero, Pilar; Alarcon, Tomas; Maini, Philip K.; Byrne, Helen

2015-10-01

Reaction-diffusion models are used to describe systems in fields as diverse as physics, chemistry, ecology and biology. The fundamental quantities in such models are individual entities such as atoms and molecules, bacteria, cells or animals, which move and/or react in a stochastic manner. If the number of entities is large, accounting for each individual is inefficient, and often partial differential equation (PDE) models are used in which the stochastic behaviour of individuals is replaced by a description of the averaged, or mean behaviour of the system. In some situations the number of individuals is large in certain regions and small in others. In such cases, a stochastic model may be inefficient in one region, and a PDE model inaccurate in another. To overcome this problem, we develop a scheme which couples a stochastic reaction-diffusion system in one part of the domain with its mean field analogue, i.e. a discretised PDE model, in the other part of the domain. The interface in between the two domains occupies exactly one lattice site and is chosen such that the mean field description is still accurate there. In this way errors due to the flux between the domains are small. Our scheme can account for multiple dynamic interfaces separating multiple stochastic and deterministic domains, and the coupling between the domains conserves the total number of particles. The method preserves stochastic features such as extinction not observable in the mean field description, and is significantly faster to simulate on a computer than the pure stochastic model.

Hybrid approaches for multiple-species stochastic reaction-diffusion models.

KAUST Repository

Spill, Fabian; Guerrero, Pilar; Alarcon, Tomas; Maini, Philip K; Byrne, Helen

2015-01-01

Reaction-diffusion models are used to describe systems in fields as diverse as physics, chemistry, ecology and biology. The fundamental quantities in such models are individual entities such as atoms and molecules, bacteria, cells or animals, which move and/or react in a stochastic manner. If the number of entities is large, accounting for each individual is inefficient, and often partial differential equation (PDE) models are used in which the stochastic behaviour of individuals is replaced by a description of the averaged, or mean behaviour of the system. In some situations the number of individuals is large in certain regions and small in others. In such cases, a stochastic model may be inefficient in one region, and a PDE model inaccurate in another. To overcome this problem, we develop a scheme which couples a stochastic reaction-diffusion system in one part of the domain with its mean field analogue, i.e. a discretised PDE model, in the other part of the domain. The interface in between the two domains occupies exactly one lattice site and is chosen such that the mean field description is still accurate there. In this way errors due to the flux between the domains are small. Our scheme can account for multiple dynamic interfaces separating multiple stochastic and deterministic domains, and the coupling between the domains conserves the total number of particles. The method preserves stochastic features such as extinction not observable in the mean field description, and is significantly faster to simulate on a computer than the pure stochastic model.

Hybrid approaches for multiple-species stochastic reaction-diffusion models.

KAUST Repository

Spill, Fabian

2015-10-01

Reaction-diffusion models are used to describe systems in fields as diverse as physics, chemistry, ecology and biology. The fundamental quantities in such models are individual entities such as atoms and molecules, bacteria, cells or animals, which move and/or react in a stochastic manner. If the number of entities is large, accounting for each individual is inefficient, and often partial differential equation (PDE) models are used in which the stochastic behaviour of individuals is replaced by a description of the averaged, or mean behaviour of the system. In some situations the number of individuals is large in certain regions and small in others. In such cases, a stochastic model may be inefficient in one region, and a PDE model inaccurate in another. To overcome this problem, we develop a scheme which couples a stochastic reaction-diffusion system in one part of the domain with its mean field analogue, i.e. a discretised PDE model, in the other part of the domain. The interface in between the two domains occupies exactly one lattice site and is chosen such that the mean field description is still accurate there. In this way errors due to the flux between the domains are small. Our scheme can account for multiple dynamic interfaces separating multiple stochastic and deterministic domains, and the coupling between the domains conserves the total number of particles. The method preserves stochastic features such as extinction not observable in the mean field description, and is significantly faster to simulate on a computer than the pure stochastic model.

Hepatitis C virus NS4B carboxy terminal domain is a membrane binding domain

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Spaan Willy JM

2009-05-01

Full Text Available Abstract Background Hepatitis C virus (HCV induces membrane rearrangements during replication. All HCV proteins are associated to membranes, pointing out the importance of membranes for HCV. Non structural protein 4B (NS4B has been reported to induce cellular membrane alterations like the membranous web. Four transmembrane segments in the middle of the protein anchor NS4B to membranes. An amphipatic helix at the amino-terminus attaches to membranes as well. The carboxy-terminal domain (CTD of NS4B is highly conserved in Hepaciviruses, though its function remains unknown. Results A cytosolic localization is predicted for the NS4B-CTD. However, using membrane floatation assays and immunofluorescence, we now show targeting of the NS4B-CTD to membranes. Furthermore, a profile-profile search, with an HCV NS4B-CTD multiple sequence alignment, indicates sequence similarity to the membrane binding domain of prokaryotic D-lactate dehydrogenase (d-LDH. The crystal structure of E. coli d-LDH suggests that the region similar to NS4B-CTD is located in the membrane binding domain (MBD of d-LDH, implying analogy in membrane association. Targeting of d-LDH to membranes occurs via electrostatic interactions of positive residues on the outside of the protein with negative head groups of lipids. To verify that anchorage of d-LDH MBD and NS4B-CTD is analogous, NS4B-CTD mutants were designed to disrupt these electrostatic interactions. Membrane association was confirmed by swopping the membrane contacting helix of d-LDH with the corresponding domain of the 4B-CTD. Furthermore, the functionality of these residues was tested in the HCV replicon system. Conclusion Together these data show that NS4B-CTD is associated to membranes, similar to the prokaryotic d-LDH MBD, and is important for replication.

Conformational analysis of isolated domains of Helicobacter pylori CagA.

Directory of Open Access Journals (Sweden)

Amanda P Woon

Full Text Available The CagA protein of Helicobacter pylori is associated with increased virulence and gastric cancer risk. CagA is translocated into the host cell by a H. pylori type IV secretion system via mechanisms that are poorly understood. Translocated CagA interacts with numerous host factors, altering a variety of host signalling pathways. The recently determined crystal structure of C-terminally-truncated CagA indicated the presence of two domains: the smaller, flexible N-terminal domain and the larger, middle domain. In this study, we have investigated the conformation, oligomeric state and stability of the N-terminal, middle and glutamate-proline-isoleucine-tyrosine-alanine (EPIYA-repeats domains. All three domains are monomeric, suggesting that the multimerisation of CagA observed in infected cells is likely to be mediated not by CagA itself but by its interacting partners. The middle and the C-terminal domains, but not the N-terminal domain, are capable of refolding spontaneously upon heat denaturation, lending support to the hypothesis that unfolded CagA is threaded C-terminus first through the type IV secretion channel with its N-terminal domain, which likely requires interactions with other domains to refold, being threaded last. Our findings also revealed that the C-terminal EPIYA-repeats domain of CagA exists in an intrinsically disordered premolten globule state with regions in PPII conformation--a feature that is shared by many scaffold proteins that bind multiple protein components of signalling pathways. Taken together, these results provide a deeper understanding of the physicochemical properties of CagA that underpin its complex cellular and oncogenic functions.

Making Sense of the Abstraction Hierarchy in the Power Plant Domain

DEFF Research Database (Denmark)

Lind, Morten

2003-01-01

The paper discusses the abstraction hierarchy proposed by Rasmussen [(1986) Information processing and human-machine interaction, North-Holland] for design of human-machine interfaces for supervisory control. The purpose of the abstraction hierarchy is to represent a work domain by multiple levels...... of means-end and part-whole abstractions. It is argued in the paper that the abstraction hierarchy suffers from both methodological and conceptual problems. A cluster of selected problems are analyzed and illustrated by concrete examples from the power plant domain. It is concluded that the semantics...... in the model-building process. It is also pointed out that attempts to clarify the semantics of the abstraction hierarchy will invariably reduce the range of work domains where it can be applied....

Multiple domains of fission yeast Cdc19p (MCM2) are required for its association with the core MCM complex.

Science.gov (United States)

Sherman, D A; Pasion, S G; Forsburg, S L

1998-07-01

The members of the MCM protein family are essential eukaryotic DNA replication factors that form a six-member protein complex. In this study, we use antibodies to four MCM proteins to investigate the structure of and requirements for the formation of fission yeast MCM complexes in vivo, with particular regard to Cdc19p (MCM2). Gel filtration analysis shows that the MCM protein complexes are unstable and can be broken down to subcomplexes. Using coimmunoprecipitation, we find that Mis5p (MCM6) and Cdc21p (MCM4) are tightly associated with one another in a core complex with which Cdc19p loosely associates. Assembly of Cdc19p with the core depends upon Cdc21p. Interestingly, there is no obvious change in Cdc19p-containing MCM complexes through the cell cycle. Using a panel of Cdc19p mutants, we find that multiple domains of Cdc19p are required for MCM binding. These studies indicate that MCM complexes in fission yeast have distinct substructures, which may be relevant for function.

Older Adults with Mild Cognitive Impairments Show Less Driving Errors after a Multiple Sessions Simulator Training Program but Do Not Exhibit Long Term Retention.

Science.gov (United States)

Teasdale, Normand; Simoneau, Martin; Hudon, Lisa; Germain Robitaille, Mathieu; Moszkowicz, Thierry; Laurendeau, Denis; Bherer, Louis; Duchesne, Simon; Hudon, Carol

2016-01-01

The driving performance of individuals with mild cognitive impairment (MCI) is suboptimal when compared to healthy older adults. It is expected that the driving will worsen with the progression of the cognitive decline and thus, whether or not these individuals should continue to drive is a matter of debate. The aim of the study was to provide support to the claim that individuals with MCI can benefit from a training program and improve their overall driving performance in a driving simulator. Fifteen older drivers with MCI participated in five training sessions in a simulator (over a 21-day period) and in a 6-month recall session. During training, they received automated auditory feedback on their performance when an error was noted about various maneuvers known to be suboptimal in MCI individuals (for instance, weaving, omitting to indicate a lane change, to verify a blind spot, or to engage in a visual search before crossing an intersection). The number of errors was compiled for eight different maneuvers for all sessions. For the initial five sessions, a gradual and significant decrease in the number of errors was observed, indicating learning and safer driving. The level of performance, however, was not maintained at the 6-month recall session. Nevertheless, the initial learning observed opens up possibilities to undertake more regular interventions to maintain driving skills and safe driving in MCI individuals.

SH2 Domains Serve as Lipid-Binding Modules for pTyr-Signaling Proteins.

Science.gov (United States)

Park, Mi-Jeong; Sheng, Ren; Silkov, Antonina; Jung, Da-Jung; Wang, Zhi-Gang; Xin, Yao; Kim, Hyunjin; Thiagarajan-Rosenkranz, Pallavi; Song, Seohyeon; Yoon, Youngdae; Nam, Wonhee; Kim, Ilshin; Kim, Eui; Lee, Dong-Gyu; Chen, Yong; Singaram, Indira; Wang, Li; Jang, Myoung Ho; Hwang, Cheol-Sang; Honig, Barry; Ryu, Sungho; Lorieau, Justin; Kim, You-Me; Cho, Wonhwa

2016-04-07

The Src-homology 2 (SH2) domain is a protein interaction domain that directs myriad phosphotyrosine (pY)-signaling pathways. Genome-wide screening of human SH2 domains reveals that ∼90% of SH2 domains bind plasma membrane lipids and many have high phosphoinositide specificity. They bind lipids using surface cationic patches separate from pY-binding pockets, thus binding lipids and the pY motif independently. The patches form grooves for specific lipid headgroup recognition or flat surfaces for non-specific membrane binding and both types of interaction are important for cellular function and regulation of SH2 domain-containing proteins. Cellular studies with ZAP70 showed that multiple lipids bind its C-terminal SH2 domain in a spatiotemporally specific manner and thereby exert exquisite spatiotemporal control over its protein binding and signaling activities in T cells. Collectively, this study reveals how lipids control SH2 domain-mediated cellular protein-protein interaction networks and suggest a new strategy for therapeutic modulation of pY-signaling pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

Mapping the structural and dynamical features of multiple p53 DNA binding domains: insights into loop 1 intrinsic dynamics.

Directory of Open Access Journals (Sweden)

Suryani Lukman

Full Text Available The transcription factor p53 regulates cellular integrity in response to stress. p53 is mutated in more than half of cancerous cells, with a majority of the mutations localized to the DNA binding domain (DBD. In order to map the structural and dynamical features of the DBD, we carried out multiple copy molecular dynamics simulations (totaling 0.8 μs. Simulations show the loop 1 to be the most dynamic element among the DNA-contacting loops (loops 1-3. Loop 1 occupies two major conformational states: extended and recessed; the former but not the latter displays correlations in atomic fluctuations with those of loop 2 (~24 Å apart. Since loop 1 binds to the major groove whereas loop 2 binds to the minor groove of DNA, our results begin to provide some insight into the possible mechanism underpinning the cooperative nature of DBD binding to DNA. We propose (1 a novel mechanism underlying the dynamics of loop 1 and the possible tread-milling of p53 on DNA and (2 possible mutations on loop 1 residues to restore the transcriptional activity of an oncogenic mutation at a distant site.

Multi-method analysis of MRI images in early diagnostics of Alzheimer's disease.

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Robin Wolz

Full Text Available The role of structural brain magnetic resonance imaging (MRI is becoming more and more emphasized in the early diagnostics of Alzheimer's disease (AD. This study aimed to assess the improvement in classification accuracy that can be achieved by combining features from different structural MRI analysis techniques. Automatically estimated MR features used are hippocampal volume, tensor-based morphometry, cortical thickness and a novel technique based on manifold learning. Baseline MRIs acquired from all 834 subjects (231 healthy controls (HC, 238 stable mild cognitive impairment (S-MCI, 167 MCI to AD progressors (P-MCI, 198 AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI database were used for evaluation. We compared the classification accuracy achieved with linear discriminant analysis (LDA and support vector machines (SVM. The best results achieved with individual features are 90% sensitivity and 84% specificity (HC/AD classification, 64%/66% (S-MCI/P-MCI and 82%/76% (HC/P-MCI with the LDA classifier. The combination of all features improved these results to 93% sensitivity and 85% specificity (HC/AD, 67%/69% (S-MCI/P-MCI and 86%/82% (HC/P-MCI. Compared with previously published results in the ADNI database using individual MR-based features, the presented results show that a comprehensive analysis of MRI images combining multiple features improves classification accuracy and predictive power in detecting early AD. The most stable and reliable classification was achieved when combining all available features.

MUPBED - interworking challenges in a multi-domain and multi-technology network environment

DEFF Research Database (Denmark)

Foisel, Hans-Martin; Spaeth, Jan; Cavazzoni, Carlo

2007-01-01

Todays data transport networks are evolving continuously towards customer oriented and application aware networks. This evolution happens in Europe in a highly diverse network environment, covering multiple network domains, layers, technologies, control and management approaches. In this paper...

Everyday episodic memory in amnestic mild cognitive impairment: a preliminary investigation.

Science.gov (United States)

Irish, Muireann; Lawlor, Brian A; Coen, Robert F; O'Mara, Shane M

2011-08-04

Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory), associative memory (face-name pairings), spatial memory (route learning and recall), and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD. The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months), 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD. As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time.

Everyday episodic memory in amnestic mild cognitive impairment: a preliminary investigation

Directory of Open Access Journals (Sweden)

Lawlor Brian A

2011-08-01

Full Text Available Abstract Background Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD and is also a defining feature of amnestic Mild Cognitive Impairment (MCI, which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory, associative memory (face-name pairings, spatial memory (route learning and recall, and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD. Results The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months, 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD. Conclusions As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time.

A designated centre for people with disabilities operated by Ability West, Galway

LENUS (Irish Health Repository)

Irish, Muireann

2011-08-04

Abstract Background Decline in episodic memory is one of the hallmark features of Alzheimer\\'s disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient\\'s daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants\\' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory), associative memory (face-name pairings), spatial memory (route learning and recall), and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD. Results The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months), 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD. Conclusions As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time.

A designated centre for people with disabilities operated by St John of God Community Services Limited, Louth

LENUS (Irish Health Repository)

Irish, Muireann

2011-08-04

Abstract Background Decline in episodic memory is one of the hallmark features of Alzheimer\\'s disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient\\'s daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants\\' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory), associative memory (face-name pairings), spatial memory (route learning and recall), and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD. Results The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months), 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD. Conclusions As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time.

Everyday episodic memory in amnestic Mild Cognitive Impairment: a preliminary investigation

LENUS (Irish Health Repository)

Irish, Muireann

2011-08-04

Abstract Background Decline in episodic memory is one of the hallmark features of Alzheimer\\'s disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient\\'s daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants\\' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory), associative memory (face-name pairings), spatial memory (route learning and recall), and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD. Results The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months), 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD. Conclusions As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time.

Identification of the functional domains of ANT-1, a novel coactivator of the androgen receptor

International Nuclear Information System (INIS)

Fan Shuli; Goto, Kiminobu; Chen Guangchun; Morinaga, Hidetaka; Nomura, Masatoshi; Okabe, Taijiro; Nawata, Hajime; Yanase, Toshihiko

2006-01-01

Previously, we identified a transcriptional coactivator for the activation function-1 (AF-1) domain of the human androgen receptor (AR) and designated it androgen receptor N-terminal domain transactivating protein-1 (ANT-1). This coactivator, which contains multiple tetratricopeptide repeat (TPR) motifs from amino acid (aa) 294, is identical to a component of U5 small nuclear ribonucleoprotein particles and binds specifically to the AR or glucocorticoid receptor. Here, we identified four distinct functional domains. The AR-AF-1-binding domain, which bound to either aa 180-360 or 360-532 in AR-AF-1, clearly overlapped with TAU-1 and TAU-5. This domain and the subnuclear speckle formation domain in ANT-1 were assigned within the TPR motifs, while the transactivating and nuclear localization signal domains resided within the N-terminal sequence. The existence of these functional domains may further support the idea that ANT-1 can function as an AR-AF-1-specific coactivator while mediating a transcription-splicing coupling

The domain architecture of large guanine nucleotide exchange factors for the small GTP-binding protein Arf

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Geldner Niko

2005-02-01

Full Text Available Abstract Background Small G proteins, which are essential regulators of multiple cellular functions, are activated by guanine nucleotide exchange factors (GEFs that stimulate the exchange of the tightly bound GDP nucleotide by GTP. The catalytic domain responsible for nucleotide exchange is in general associated with non-catalytic domains that define the spatio-temporal conditions of activation. In the case of small G proteins of the Arf subfamily, which are major regulators of membrane trafficking, GEFs form a heterogeneous family whose only common characteristic is the well-characterized Sec7 catalytic domain. In contrast, the function of non-catalytic domains and how they regulate/cooperate with the catalytic domain is essentially unknown. Results Based on Sec7-containing sequences from fully-annotated eukaryotic genomes, including our annotation of these sequences from Paramecium, we have investigated the domain architecture of large ArfGEFs of the BIG and GBF subfamilies, which are involved in Golgi traffic. Multiple sequence alignments combined with the analysis of predicted secondary structures, non-structured regions and splicing patterns, identifies five novel non-catalytic structural domains which are common to both subfamilies, revealing that they share a conserved modular organization. We also report a novel ArfGEF subfamily with a domain organization so far unique to alveolates, which we name TBS (TBC-Sec7. Conclusion Our analysis unifies the BIG and GBF subfamilies into a higher order subfamily, which, together with their being the only subfamilies common to all eukaryotes, suggests that they descend from a common ancestor from which species-specific ArfGEFs have subsequently evolved. Our identification of a conserved modular architecture provides a background for future functional investigation of non-catalytic domains.

Writing Impairments in Japanese Patients with Mild Cognitive Impairment and with Mild Alzheimer's Disease

Directory of Open Access Journals (Sweden)

Atsuko Hayashi

2015-09-01

Full Text Available Background/Aims: We investigated writing abilities in patients with the amnestic type of mild cognitive impairment (aMCI and mild Alzheimer's disease (AD. To examine the earliest changes in writing function, we used writing tests for both words and sentences with different types of Japanese characters (Hiragana, Katakana, and Kanji. Methods: A total of 25 aMCI patients, 38 AD patients, and 22 healthy controls performed writing to dictation for Kana and Kanji words, copied Kanji words, and wrote in response to a picture story task. Analysis of variance was used to test the subject group effects on the scores in the above writing tasks. Results: For the written Kanji words, the mild AD group performed worse than the aMCI group and the controls, but there was no difference between the aMCI group and the controls. For the picture story writing task, the mild AD and aMCI groups performed worse than the controls, but the difference between the AD and the aMCI groups was not significant. Conclusions: The mild AD group showed defects in writing Kanji characters, and the aMCI group showed impairments in narrative writing. Our study suggests that narrative writing, which demands complex integration of multiple cognitive functions, can be used to detect the subtle writing deficits in aMCI patients.

The BRCT domain is a phospho-protein binding domain.

Science.gov (United States)

Yu, Xiaochun; Chini, Claudia Christiano Silva; He, Miao; Mer, Georges; Chen, Junjie

2003-10-24

The carboxyl-terminal domain (BRCT) of the Breast Cancer Gene 1 (BRCA1) protein is an evolutionarily conserved module that exists in a large number of proteins from prokaryotes to eukaryotes. Although most BRCT domain-containing proteins participate in DNA-damage checkpoint or DNA-repair pathways, or both, the function of the BRCT domain is not fully understood. We show that the BRCA1 BRCT domain directly interacts with phosphorylated BRCA1-Associated Carboxyl-terminal Helicase (BACH1). This specific interaction between BRCA1 and phosphorylated BACH1 is cell cycle regulated and is required for DNA damage-induced checkpoint control during the transition from G2 to M phase of the cell cycle. Further, we show that two other BRCT domains interact with their respective physiological partners in a phosphorylation-dependent manner. Thirteen additional BRCT domains also preferentially bind phospho-peptides rather than nonphosphorylated control peptides. These data imply that the BRCT domain is a phospho-protein binding domain involved in cell cycle control.

[The influence of the pre-hospital application of non-invasive measurements of carboxyhemoglobin in the practice of emergency medical services in multiple and mass casualty incidents (MCI)--a case report].

Science.gov (United States)

Gałazkowski, Robert; Wejnarski, Arkadiusz; Baumberg, Ignacy; Świeżewski, Stanisław; Timler, Dariusz

2014-01-01

In 2013 a fire broke out in the Nursing Home (NH) in the Henryszew village 5 km away from the district hospital in Zyrardów. At the time of the incident 52 residents and 16 staff members were present in the building. Due to a large number of casualties, the occurrence was classified as a potentially mass casualty incident (MCI). Troops of the State Fire Brigade, Paramedic Rescue Squads, choppers of the Helicopter Emergency Medical Service, the Police, and the NH staff took part in the rescue operation. The priority was given to the evacuation of the NH residents carried out by the NH staff and firefighters, extinguishing the fire, as well as to primary and secondary survey triage. Due to the pre-accident health state of the victims, the latter posed a considerable difficulty. A decisive role was played by the need to conduct non-invasive measurements of carboxyhemoglobin in all the casualties, which then made it possible to adequately diagnose the patients and implement proper procedures. The rescue operation was correctly followed although it proved to be a serious logistical and technical undertaking for the participating emergency services. The residents were not found to be suffering from carbon monoxide poisoning, therefore 46 of the residents safely returned to the building. The fact that all the Paramedic Rescue Squads were equipped with medical triage sets and were able to conduct non-invasive measurements of carboxyhemoglobin made it possible to introduce effective procedures in the cases of suspected carbon monoxide poisoning and abandon costly and complicated organisational procedures when they proved to be unnecessary.

Clock domain crossing modules for OCP-style read/write interfaces

DEFF Research Database (Denmark)

Herlev, Mathias; Sparsø, Jens

The open core protocol (OCP) is an openly licensed, configurable, and scalable interface protocol for on-chip subsystem communications. The protocol defines read and write transactions from a master towards a slave across a point-to-point connection and the protocol assumes a single common clock....... This paper presents the design of two OCP clock domain crossing interface modules, that can be used to construct systems with multiple clock domains. One module (called OCPio) supports a single word read-write interface and the other module (called OCPburst) supports a four word burst read-write interface......-style read-write transaction interfaces. An OCP interface typically has control signals related to both the master issuing a read or write request and the slave producing a response. If all these control signals are passed across the clock domain boundary and synchronized it may add significant latency...

B-spline Collocation with Domain Decomposition Method

International Nuclear Information System (INIS)

Hidayat, M I P; Parman, S; Ariwahjoedi, B

2013-01-01

A global B-spline collocation method has been previously developed and successfully implemented by the present authors for solving elliptic partial differential equations in arbitrary complex domains. However, the global B-spline approximation, which is simply reduced to Bezier approximation of any degree p with C 0 continuity, has led to the use of B-spline basis of high order in order to achieve high accuracy. The need for B-spline bases of high order in the global method would be more prominent in domains of large dimension. For the increased collocation points, it may also lead to the ill-conditioning problem. In this study, overlapping domain decomposition of multiplicative Schwarz algorithm is combined with the global method. Our objective is two-fold that improving the accuracy with the combination technique, and also investigating influence of the combination technique to the employed B-spline basis orders with respect to the obtained accuracy. It was shown that the combination method produced higher accuracy with the B-spline basis of much lower order than that needed in implementation of the initial method. Hence, the approximation stability of the B-spline collocation method was also increased.

Levels and domains in personality: an introduction.

Science.gov (United States)

Emmons, R A

1995-09-01

This special issue is centered around the problem of levels and domains in personality functioning. What kind of constructs--and at what levels and in what domains--are needed to understand what a person is like? To account for the complexity and scope of human lives, personality psychologists have traditionally put forth lists and taxonomies of factors, features, and variables that must be taken into consideration in formulating an adequate psychological portrait of the whole person. The five-factor model of personality traits has recently been offered as a comprehensive framework; however, critical analyses of the trait concept have revealed the limitations of a trait-based model of personality. Recognizing that the concept of trait is indispensable to a vital psychology of personality, this special issue aims to (a) communicate recent developments and organizational frameworks for understanding the person at multiple levels and in varied domains, and (b) articulate and elaborate units of analysis that, when combined with trait assessments, yield a psychology of personality that is commensurate with the complexity of individual functioning and that offers greater potential for the attainment of the original goals of the discipline.

The utility of focused assessment with sonography for trauma as a triage tool in multiple-casualty incidents during the second Lebanon war.

Science.gov (United States)

Beck-Razi, Nira; Fischer, Doron; Michaelson, Moshe; Engel, Ahuva; Gaitini, Diana

2007-09-01

The purpose of this study was to evaluate the role of focused assessment with sonography for trauma (FAST) as a triage tool in multiple-casualty incidents (MCIs) for a single international conflict. The charts of 849 casualties that arrived at our level 1 trauma referral center were reviewed. Casualties were initially triaged according to the Injury Severity Score at the emergency department gate. Two-hundred eighty-one physically injured patients, 215 soldiers (76.5%) and 66 civilians (23.5%), were admitted. Focused assessment with sonography for trauma was performed in 102 casualties suspected to have an abdominal injury. Sixty-eight underwent computed tomography (CT); 12 underwent laparotomy; and 28 were kept under clinical observation alone. We compared FAST results against CT, laparotomy, and clinical observation records. Focused assessment with sonography for trauma results were positive in 17 casualties and negative in 85. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of FAST were 75%, 97.6%, 88.2%, 94.1%, and 93.1%, respectively. A strong correlation between FAST and CT results, laparotomy, and clinical observation was obtained (P war conflict-related MCI, FAST enabled immediate triage of casualties to laparotomy, CT, or clinical observation. Because of its moderate sensitivity, a negative FAST result with strong clinical suspicion demands further evaluation, especially in an MCI.

Step by Step: Biology Undergraduates' Problem-Solving Procedures during Multiple-Choice Assessment.

Science.gov (United States)

Prevost, Luanna B; Lemons, Paula P

2016-01-01

This study uses the theoretical framework of domain-specific problem solving to explore the procedures students use to solve multiple-choice problems about biology concepts. We designed several multiple-choice problems and administered them on four exams. We trained students to produce written descriptions of how they solved the problem, and this allowed us to systematically investigate their problem-solving procedures. We identified a range of procedures and organized them as domain general, domain specific, or hybrid. We also identified domain-general and domain-specific errors made by students during problem solving. We found that students use domain-general and hybrid procedures more frequently when solving lower-order problems than higher-order problems, while they use domain-specific procedures more frequently when solving higher-order problems. Additionally, the more domain-specific procedures students used, the higher the likelihood that they would answer the problem correctly, up to five procedures. However, if students used just one domain-general procedure, they were as likely to answer the problem correctly as if they had used two to five domain-general procedures. Our findings provide a categorization scheme and framework for additional research on biology problem solving and suggest several important implications for researchers and instructors. © 2016 L. B. Prevost and P. P. Lemons. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

A novel gene encoding a TIG multiple domain protein is a positional candidate for autosomal recessive polycystic kidney disease.

Science.gov (United States)

Xiong, Huaqi; Chen, Yongxiong; Yi, Yajun; Tsuchiya, Karen; Moeckel, Gilbert; Cheung, Joseph; Liang, Dan; Tham, Kyi; Xu, Xiaohu; Chen, Xing-Zhen; Pei, York; Zhao, Zhizhuang Jeo; Wu, Guanqing

2002-07-01

Autosomal recessive polycystic kidney disease (ARPKD) is a common hereditary renal cystic disease in infants and children. By genetic linkage analyses, the gene responsible for this disease, termed polycystic kidney and hepatic disease 1 (PKHD1), was mapped on human chromosome 6p21.1-p12, and has been further localized to a 1-cM genetic interval flanked by the D6S1714/D6S243 (telomeric) and D6S1024 (centromeric) markers. We recently identified a novel gene in this genetic interval from kidney cDNA, using cloning strategies. The gene PKHD1 (PKHD1-tentative) encodes a novel 3396-amino-acid protein with no apparent homology with any known proteins. We named its gene product "tigmin" because it contains multiple TIG domains, which usually are seen in proteins containing immunoglobulin-like folds. PKHD1 encodes an 11.6-kb transcript and is composed of 61 exons spanning an approximately 365-kb genomic region on chromosome 6p12-p11.2 adjacent to the marker D6S1714. Northern blot analyses demonstrated that the gene has discrete bands with one peak signal at approximately 11 kb, indicating that PKHD1 is likely to have multiple alternative transcripts. PKHD1 is highly expressed in adult and infant kidneys and weakly expressed in liver in northern blot analysis. This expression pattern parallels the tissue involvement observed in ARPKD. In situ hybridization analysis further revealed that the expression of PKHD1 in the kidney is mainly localized to the epithelial cells of the collecting duct, the specific tubular segment involved in cyst formation in ARPKD. These features of PKHD1 make it a strong positional candidate gene for ARPKD.

Transient spectral domain optical coherence tomography findings in classic MEWDS: a case report.

Science.gov (United States)

Lavigne, Luciana Castro; Isaac, David Leonardo Cruvinel; Duarte Júnior, José Osório; Avila, Marcos Pereira de

2014-01-01

The purpose of this study was to describe a patient with multiple evanescent white dot syndrome (MEWDS) who presented with classic retinal findings and transient changes in outer retinal anatomy. A 20-year-old man presented with mild blurred vision in the left eye, reporting flu-like symptoms 1 week before the visual symptoms started. Fundus examination of the left eye revealed foveal granularity and multiple scattered spots deep to the retina in the posterior pole. Fluorescein angiography and indocyanine green angiography showed typical MEWDS findings. Spectral Domain Optical Coherence Tomography has shown transient changes in outer retinal anatomy with disappearance of inner segment-outer segment junction and mild attenuation of external limiting membrane. Six months later, Spectral Domain Optical Coherence Tomography has shown complete resolution with recovery of normal outer retinal aspect.

Asymptotic Behavior for a Nonlocal Diffusion Equation in Domains with Holes

Science.gov (United States)

Cortázar, Carmen; Elgueta, Manuel; Quirós, Fernando; Wolanski, Noemí

2012-08-01

The paper deals with the asymptotic behavior of solutions to a non-local diffusion equation, u t = J* u- u := Lu, in an exterior domain, Ω, which excludes one or several holes, and with zero Dirichlet data on {R^NsetminusΩ} . When the space dimension is three or more this behavior is given by a multiple of the fundamental solution of the heat equation away from the holes. On the other hand, if the solution is scaled according to its decay factor, close to the holes it behaves like a function that is L-harmonic, Lu = 0, in the exterior domain and vanishes in its complement. The height of such a function at infinity is determined through a matching procedure with the multiple of the fundamental solution of the heat equation representing the outer behavior. The inner and the outer behaviors can be presented in a unified way through a suitable global approximation.

Apicobasal domain identities of expanding tubular membranes depend on glycosphingolipid biosynthesis.

Science.gov (United States)

Zhang, Hongjie; Abraham, Nessy; Khan, Liakot A; Hall, David H; Fleming, John T; Göbel, Verena

2011-09-18

Metazoan internal organs are assembled from polarized tubular epithelia that must set aside an apical membrane domain as a lumenal surface. In a global Caenorhabditis elegans tubulogenesis screen, interference with several distinct fatty-acid-biosynthetic enzymes transformed a contiguous central intestinal lumen into multiple ectopic lumens. We show that multiple-lumen formation is caused by apicobasal polarity conversion, and demonstrate that in situ modulation of lipid biosynthesis is sufficient to reversibly switch apical domain identities on growing membranes of single post-mitotic cells, shifting lumen positions. Follow-on targeted lipid-biosynthesis pathway screens and functional genetic assays were designed to identify a putative single causative lipid species. They demonstrate that fatty-acid biosynthesis affects polarity through sphingolipid synthesis, and reveal ceramide glucosyltransferases (CGTs) as end-point biosynthetic enzymes in this pathway. Our findings identify glycosphingolipids, CGT products and obligate membrane lipids, as critical determinants of in vivo polarity and indicate that they sort new components to the expanding apical membrane.

Domain analysis

DEFF Research Database (Denmark)

Hjørland, Birger

2017-01-01

The domain-analytic approach to knowledge organization (KO) (and to the broader field of library and information science, LIS) is outlined. The article reviews the discussions and proposals on the definition of domains, and provides an example of a domain-analytic study in the field of art studies....... Varieties of domain analysis as well as criticism and controversies are presented and discussed....

Inferring domain-domain interactions from protein-protein interactions with formal concept analysis.

Directory of Open Access Journals (Sweden)

Susan Khor

Full Text Available Identifying reliable domain-domain interactions will increase our ability to predict novel protein-protein interactions, to unravel interactions in protein complexes, and thus gain more information about the function and behavior of genes. One of the challenges of identifying reliable domain-domain interactions is domain promiscuity. Promiscuous domains are domains that can occur in many domain architectures and are therefore found in many proteins. This becomes a problem for a method where the score of a domain-pair is the ratio between observed and expected frequencies because the protein-protein interaction network is sparse. As such, many protein-pairs will be non-interacting and domain-pairs with promiscuous domains will be penalized. This domain promiscuity challenge to the problem of inferring reliable domain-domain interactions from protein-protein interactions has been recognized, and a number of work-arounds have been proposed. This paper reports on an application of Formal Concept Analysis to this problem. It is found that the relationship between formal concepts provides a natural way for rare domains to elevate the rank of promiscuous domain-pairs and enrich highly ranked domain-pairs with reliable domain-domain interactions. This piggybacking of promiscuous domain-pairs onto less promiscuous domain-pairs is possible only with concept lattices whose attribute-labels are not reduced and is enhanced by the presence of proteins that comprise both promiscuous and rare domains.

Inferring Domain-Domain Interactions from Protein-Protein Interactions with Formal Concept Analysis

Science.gov (United States)

Khor, Susan

2014-01-01

Identifying reliable domain-domain interactions will increase our ability to predict novel protein-protein interactions, to unravel interactions in protein complexes, and thus gain more information about the function and behavior of genes. One of the challenges of identifying reliable domain-domain interactions is domain promiscuity. Promiscuous domains are domains that can occur in many domain architectures and are therefore found in many proteins. This becomes a problem for a method where the score of a domain-pair is the ratio between observed and expected frequencies because the protein-protein interaction network is sparse. As such, many protein-pairs will be non-interacting and domain-pairs with promiscuous domains will be penalized. This domain promiscuity challenge to the problem of inferring reliable domain-domain interactions from protein-protein interactions has been recognized, and a number of work-arounds have been proposed. This paper reports on an application of Formal Concept Analysis to this problem. It is found that the relationship between formal concepts provides a natural way for rare domains to elevate the rank of promiscuous domain-pairs and enrich highly ranked domain-pairs with reliable domain-domain interactions. This piggybacking of promiscuous domain-pairs onto less promiscuous domain-pairs is possible only with concept lattices whose attribute-labels are not reduced and is enhanced by the presence of proteins that comprise both promiscuous and rare domains. PMID:24586450

Using random response input in Ibrahim Time Domain

DEFF Research Database (Denmark)

Olsen, Peter; Brincker, R.

2013-01-01

In this paper the time domain technique Ibrahim Time Domain (ITD) is used to analyze random time data. ITD is known to be a technique for identification of output only systems. The traditional formulation of ITD is claimed to be limited, when identifying closely spaced modes, because....... In this article it is showed that when using the modified ITD random time data can be analyzed. The application of the technique is displayed by a case study, with simulations and experimental data....... of the technique being Single Input Multiple Output (SIMO). It has earlier been showed that when modifying ITD with Toeplitz matrix averaging. Identification of time data with closely spaced modes is improved. In the traditional formulation of ITD the time data has to be free decays or impulse response functions...

Operational Cybersecurity Risks and Their Effect on Adoption of Additive Manufacturing in the Naval Domain

Science.gov (United States)

2017-12-01

CYBERSECURITY RISKS AND THEIR EFFECT ON ADOPTION OF ADDITIVE MANUFACTURING IN THE NAVAL DOMAIN by Michael D. Grimshaw December 2017 Thesis...OF ADDITIVE MANUFACTURING IN THE NAVAL DOMAIN 5. FUNDING NUMBERS 6. AUTHOR(S) Michael D. Grimshaw 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES...DISTRIBUTION CODE 13. ABSTRACT (maximum 200 words) Additive manufacturing (AM) has been proven to provide multiple benefits over traditional

Infected cell protein 0 functional domains and their coordination in herpes simplex virus replication

Science.gov (United States)

Gu, Haidong

2016-01-01

Herpes simplex virus 1 (HSV-1) is a ubiquitous human pathogen that establishes latent infection in ganglia neurons. Its unique life cycle requires a balanced “conquer and compromise” strategy to deal with the host anti-viral defenses. One of HSV-1 α (immediate early) gene products, infected cell protein 0 (ICP0), is a multifunctional protein that interacts with and modulates a wide range of cellular defensive pathways. These pathways may locate in different cell compartments, which then migrate or exchange factors upon stimulation, for the purpose of a concerted and effective defense. ICP0 is able to simultaneously attack multiple host pathways by either degrading key restrictive factors or modifying repressive complexes. This is a viral protein that contains an E3 ubiquitin ligase, translocates among different cell compartments and interacts with major defensive complexes. The multiple functional domains of ICP0 can work independently and at the same time coordinate with each other. Dissecting the functional domains of ICP0 and delineating the coordination of these domains will help us understand HSV-1 pathogenicity as well as host defense mechanisms. This article focuses on describing individual ICP0 domains, their biochemical properties and their implication in HSV-1 infection. By putting individual domain functions back into the picture of host anti-viral defense network, this review seeks to elaborate the complex interactions between HSV-1 and its host. PMID:26870669

Robust Visual Knowledge Transfer via Extreme Learning Machine Based Domain Adaptation.

Science.gov (United States)

Zhang, Lei; Zhang, David

2016-08-10

We address the problem of visual knowledge adaptation by leveraging labeled patterns from source domain and a very limited number of labeled instances in target domain to learn a robust classifier for visual categorization. This paper proposes a new extreme learning machine based cross-domain network learning framework, that is called Extreme Learning Machine (ELM) based Domain Adaptation (EDA). It allows us to learn a category transformation and an ELM classifier with random projection by minimizing the -norm of the network output weights and the learning error simultaneously. The unlabeled target data, as useful knowledge, is also integrated as a fidelity term to guarantee the stability during cross domain learning. It minimizes the matching error between the learned classifier and a base classifier, such that many existing classifiers can be readily incorporated as base classifiers. The network output weights cannot only be analytically determined, but also transferrable. Additionally, a manifold regularization with Laplacian graph is incorporated, such that it is beneficial to semi-supervised learning. Extensively, we also propose a model of multiple views, referred as MvEDA. Experiments on benchmark visual datasets for video event recognition and object recognition, demonstrate that our EDA methods outperform existing cross-domain learning methods.

Prevalence of DSM-5 Mild Neurocognitive Disorder in Dementia-Free Older Adults: Results of the Population-Based LIFE-Adult-Study.

Science.gov (United States)

Luck, Tobias; Then, Francisca S; Schroeter, Matthias L; Witte, Veronica; Engel, Christoph; Loeffler, Markus; Thiery, Joachim; Villringer, Arno; Riedel-Heller, Steffi G

2017-04-01

The DSM-5 introduces mild neurocognitive disorder (miNCD) as a syndrome that recognizes the potential clinical importance of acquired cognitive deficits being too mild to qualify for diagnosis of dementia. We provide new empirical data on miNCD including total, age-, and sex-specific prevalence rates; number and types of neurocognitive domains being impaired; and diagnostic overlap with the well-established mild cognitive impairment (MCI) concept. Cross-sectional results of an observational cohort study (LIFE-Adult-Study). General population. A total of 1,080 dementia-free individuals, aged 60-79 years. We calculated weighted point prevalence rates with confidence intervals (95% CI) for miNCD and analyzed diagnostic overlap between miNCD and MCI by calculating overall percentage agreement and Cohen's kappa coefficient. Weighted total prevalence of miNCD was 20.3% (95% CI: 17.8-23.0). Prevalence was similar in both sexes, but significantly higher in older age. Two-thirds (66.2%) of the individuals with miNCD showed impairment restricted to only one out of six possible neurocognitive domains. Learning and memory was the most frequently (38.3%) impaired domain in all miNCD-cases, followed by social cognition (26.1%). Analysis of diagnostic overlap with MCI yielded an overall agreement of 98.6% and a kappa of 0.959. By considering all six predefined neurocognitive domains, our study observed a substantial proportion of dementia-free older adults having miNCD. Provision of information on the underlying etiology/ies may be of prime importance in future studies aiming at evaluating the clinical relevance of the miNCD syndrome. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

A study on group decision-making based fault multi-symptom-domain consensus diagnosis

International Nuclear Information System (INIS)

He Yongyong; Chu Fulei; Zhong Binglin

2001-01-01

In the field of fault diagnosis for rotating machines, the conventional methods or the neural network based methods are mainly single symptom domain based methods, and the diagnosis accuracy of which is not always satisfactory. In this paper, in order to utilize multiple symptom domains to improve the diagnosis accuracy, an idea of fault multi-symptom-domain consensus diagnosis is developed. From the point of view of the group decision-making, two particular multi-symptom-domain diagnosis strategies are proposed. The proposed strategies use BP (Back-Propagation) neural networks as diagnosis models in various symptom domains, and then combine the outputs of these networks by two combination schemes, which are based on Dempster-Shafer evidence theory and fuzzy integral theory, respectively. Finally, a case study pertaining to the fault diagnosis for rotor-bearing systems is given in detail, and the results show that the proposed diagnosis strategies are feasible and more efficient than conventional stacked-vector methods

On the efficiency of BGP-TE extensions for GMPLS multi-domain routing

DEFF Research Database (Denmark)

Manolova, Anna Vasileva; Ruepp, Sarah Renée; Buron, Jakob Due

2009-01-01

This paper evaluates the efficiency of set of modifications to the border gateway protocol (BGP) which aim at providing flexible traffic engineering (TE) across multiple GMPLS domains. A short overview and analysis of existing proposals for BGP-TE extensions is presented. Based on that, three...... modifications are proposed for support of multi-domain TE: an end-to-end path-specific TE attribute, a border node attribute and a behavioral modification of the protocol. Via analysis and extensive simulations we show that the proposed enhancements successfully improve the most significant BGP drawbacks...

End States, Ladder Compounds, and Domain-Wall Fermions

International Nuclear Information System (INIS)

Creutz, M.

1999-01-01

A magnetic field applied to a cross-linked ladder compound can generate isolated electronic states bound to the ends of the chain. After exploring the interference phenomena responsible, I discuss a connection to the domain-wall approach to chiral fermions in lattice gauge theory. The robust nature of the states under small variations of the bond strengths is tied to chiral symmetry and the multiplicative renormalization of fermion masses. copyright 1999 The American Physical Society

Some problems in operator theory on bounded symmetric domains

Czech Academy of Sciences Publication Activity Database

Engliš, Miroslav

2004-01-01

Roč. 81, č. 1 (2004), s. 51-71 ISSN 0167-8019. [Representations of Lie groups, harmonic analysis on homogeneous spaces and quantization. Leiden, 07.12.2002-13.12.2002] R&D Projects: GA ČR GA201/03/0041 Institutional research plan: CEZ:AV0Z1019905 Keywords : homogeneous multiplication operators * bounded symmetric domains Subject RIV: BA - General Mathematics Impact factor: 0.354, year: 2004

Domain-restricted mutation analysis to identify novel driver events in human cancer

Directory of Open Access Journals (Sweden)

Sanket Desai

2017-10-01

Full Text Available Analysis of mutational spectra across various cancer types has given valuable insights into tumorigenesis. Different approaches have been used to identify novel drivers from the set of somatic mutations, including the methods which use sequence conservation, geometric localization and pathway information. Recent computational methods suggest use of protein domain information for analysis and understanding of the functional consequence of non-synonymous mutations. Similarly, evidence suggests recurrence at specific position in proteins is robust indicators of its functional impact. Building on this, we performed a systematic analysis of TCGA exome derived somatic mutations across 6089 PFAM domains and significantly mutated domains were identified using randomization approach. Multiple alignment of individual domain allowed us to prioritize for conserved residues mutated at analogous positions across different proteins in a statistically disciplined manner. In addition to the known frequently mutated genes, this analysis independently identifies low frequency Meprin and TRAF-Homology (MATH domain in Speckle Type BTB/POZ (SPOP protein, in prostate adenocarcinoma. Results from this analysis will help generate hypotheses about the downstream molecular mechanism resulting in cancer phenotypes.

A novel role for the TIR domain in association with pathogen-derived elicitors.

Directory of Open Access Journals (Sweden)

Tessa M Burch-Smith

2007-03-01

Full Text Available Plant innate immunity is mediated by Resistance (R proteins, which bear a striking resemblance to animal molecules of similar function. Tobacco N is a TIR-NB-LRR R gene that confers resistance to Tobacco mosaic virus, specifically the p50 helicase domain. An intriguing question is how plant R proteins recognize the presence of pathogen-derived Avirulence (Avr elicitor proteins. We have used biochemical cell fraction and immunoprecipitation in addition to confocal fluorescence microscopy of living tissue to examine the association between N and p50. Surprisingly, both N and p50 are cytoplasmic and nuclear proteins, and N's nuclear localization is required for its function. We also demonstrate an in planta association between N and p50. Further, we show that N's TIR domain is critical for this association, and indeed, it alone can associate with p50. Our results differ from current models for plant innate immunity that propose detection is mediated solely through the LRR domains of these molecules. The data we present support an intricate process of pathogen elicitor recognition by R proteins involving multiple subcellular compartments and the formation of multiple protein complexes.

Facile construction of a random protein domain insertion library using an engineered transposon.

Science.gov (United States)

Shah, Vandan; Pierre, Brennal; Kim, Jin Ryoun

2013-01-15

Insertional fusion between multiple protein domains represents a novel means of creating integrated functionalities. Currently, there is no robust guideline for selection of insertion sites ensuring the desired functional outcome of insertional fusion. Therefore, construction and testing of random domain insertion libraries, in which a host protein domain is randomly inserted into a guest protein domain, significantly benefit extensive exploration of sequence spaces for insertion sites. Short peptide residues are usually introduced between protein domains to alleviate structural conflicts, and the interdomain linker residues may affect the functional outcome of protein insertion complexes. Unfortunately, optimal control of interdomain linker residues is not always available in conventional methods used to construct random domain insertion libraries. Moreover, most conventional methods employ blunt-end rather than sticky-end ligation between host and guest DNA fragments, thus lowering library construction efficiency. Here, we report the facile construction of random domain insertion libraries using an engineered transposon. We show that random domain insertion with optimal control of interdomain linker residues was possible with our engineered transposon-based method. In addition, our method employs sticky-end rather than blunt-end ligation between host and guest DNA fragments, thus allowing for facile construction of relatively large sized libraries. Copyright © 2012 Elsevier Inc. All rights reserved.

Documentation and localization of force-mediated filamin A domain perturbations in moving cells

Science.gov (United States)

Nakamura, Fumihiko; Song, Mia; Hartwig, John H.; Stossel, Thomas P.

2014-08-01

Endogenously and externally generated mechanical forces influence diverse cellular activities, a phenomenon defined as mechanotransduction. Deformation of protein domains by application of stress, previously documented to alter macromolecular interactions in vitro, could mediate these effects. We engineered a photon-emitting system responsive to unfolding of two repeat domains of the actin filament (F-actin) crosslinker protein filamin A (FLNA) that binds multiple partners involved in cell signalling reactions and validated the system using F-actin networks subjected to myosin-based contraction. Expressed in cultured cells, the sensor-containing FLNA construct reproducibly reported FLNA domain unfolding strikingly localized to dynamic, actively protruding, leading cell edges. The unfolding signal depends upon coherence of F-actin-FLNA networks and is enhanced by stimulating cell contractility. The results establish protein domain distortion as a bona fide mechanism for mechanotransduction in vivo.

Multiprocessor system with multiple concurrent modes of execution

Science.gov (United States)

Ahn, Daniel; Ceze, Luis H; Chen, Dong; Gara, Alan; Heidelberger, Philip; Ohmacht, Martin

2013-12-31

A multiprocessor system supports multiple concurrent modes of speculative execution. Speculation identification numbers (IDs) are allocated to speculative threads from a pool of available numbers. The pool is divided into domains, with each domain being assigned to a mode of speculation. Modes of speculation include TM, TLS, and rollback. Allocation of the IDs is carried out with respect to a central state table and using hardware pointers. The IDs are used for writing different versions of speculative results in different ways of a set in a cache memory.

Correlated Longitudinal Changes across Linguistic, Achievement, and Psychomotor Domains in Early Childhood: Evidence for a Global Dimension of Development

Science.gov (United States)

Rhemtulla, Mijke; Tucker-Drob, Elliot M.

2011-01-01

An important question within developmental psychology concerns the extent to which the maturational gains that children make across multiple diverse domains of functioning can be attributed to global (domain-general) developmental processes. The present study investigated this question by examining the extent to which individual differences in…

An Architecture to Manage Incoming Traffic of Inter-Domain Routing Using OpenFlow Networks

Directory of Open Access Journals (Sweden)

Walber José Adriano Silva

2018-04-01

Full Text Available The Border Gateway Protocol (BGP is the current state-of-the-art inter-domain routing between Autonomous Systems (ASes. Although BGP has different mechanisms to manage outbound traffic in an AS domain, it lacks an efficient tool for inbound traffic control from transit ASes such as Internet Service Providers (ISPs. For inter-domain routing, the BGP’s destination-based forwarding paradigm limits the granularity of distributing the network traffic among the multiple paths of the current Internet topology. Thus, this work offered a new architecture to manage incoming traffic in the inter-domain using OpenFlow networks. The architecture explored direct inter-domain communication to exchange control information and the functionalities of the OpenFlow protocol. Based on the achieved results of the size of exchanging messages, the proposed architecture is not only scalable, but also capable of performing load balancing for inbound traffic using different strategies.

.Gov Domains API

Data.gov (United States)

General Services Administration — This dataset offers the list of all .gov domains, including state, local, and tribal .gov domains. It does not include .mil domains, or other federal domains outside...

The influence of the pre-hospital application of non-invasive measurements of carboxyhemoglobin in the practice of emergency medical services in multiple and mass casualty incidents (MCI – A case report

Directory of Open Access Journals (Sweden)

Robert Gałązkowski

2014-04-01

Full Text Available In 2013 a fire broke out in the Nursing Home (NH in the Henryszew village 5 km away from the district hospital in Żyrardów. At the time of the incident 52 residents and 16 staff members were present in the building. Due to a large number of casualties, the occurrence was classified as a potentially mass casualty incident (MCI. Troops of the State Fire Brigade, Paramedic Rescue Squads, choppers of the Helicopter Emergency Medical Service, the Police, and the NH staff took part in the rescue operation. The priority was given to the evacuation of the NH residents carried out by the NH staff and firefighters, extinguishing the fire, as well as to primary and secondary survey triage. Due to the pre-accident health state of the victims, the latter posed a considerable difficulty. A decisive role was played by the need to conduct non-invasive measurements of carboxyhemoglobin in all the casualties, which then made it possible to adequately diagnose the patients and implement proper procedures. The rescue operation was correctly followed although it proved to be a serious logistical and technical undertaking for the participating emergency services. The residents were not found to be suffering from carbon monoxide poisoning, therefore 46 of the residents safely returned to the building. The fact that all the Paramedic Rescue Squads were equipped with medical triage sets and were able to conduct non-invasive measurements of carboxyhemoglobin made it possible to introduce effective procedures in the cases of suspected carbon monoxide poisoning and abandon costly and complicated organisational procedures when they proved to be unnecessary. Med Pr 2014;65(2:289–295

Is Divorce More Painful When Couples Have Children? Evidence From Long-Term Panel Data on Multiple Domains of Well-being.

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Leopold, Thomas; Kalmijn, Matthijs

2016-12-01

Theoretical models of the divorce process suggest that marital breakup is more painful in the presence of children, yet little is known about the role of children as a moderator of divorce effects on adult well-being. The present study addresses this gap of research based on long-term panel data from Germany (SOEP). Following individuals over several years before and after divorce, we investigated whether the impact of divorce on multiple measures of well-being varied by the presence and age of children before marital breakup. Three central findings emerged from the analysis. First, declines in well-being were sharper in the presence of children, and these moderator effects were larger if children were younger. Second, domain-specific measures of well-being revealed gender differences in the moderating role of children. Mothers sustained deeper drops in economic well-being than did fathers; the reverse was true for family well-being. Third, most of these disproportionate declines in the well-being of divorced parents did not persist in the long term given that higher rates of adaptation leveled out the gaps compared with childless divorcees.

Episodic, but not semantic, autobiographical memory is reduced in amnestic mild cognitive impairment.

Science.gov (United States)

Murphy, Kelly J; Troyer, Angela K; Levine, Brian; Moscovitch, Morris

2008-11-01

Amnestic mild cognitive impairment (aMCI) is characterized by decline in anterograde memory as measured by the ability to learn and remember new information. We investigated whether retrograde memory for autobiographical information was affected by aMCI. Eighteen control (age 66-84 years) and 17 aMCI (age 66-84 years) participants described a personal event from each of the five periods across the lifespan. These events were transcribed and scored according to procedures that separate episodic (specific happenings) from semantic (general knowledge) elements of autobiographical memory. Although both groups generated protocols of similar length, the composition of autobiographical recall differentiated the groups. The aMCI group protocols were characterized by reduced episodic and increased semantic information relative to the control group. Both groups showed a similar pattern of recall across time periods, with no evidence that the aMCI group had more difficulty recalling recent, rather than remote, life events. These results indicate that episodic and semantic autobiographical memories are differentially affected by the early brain changes associated with aMCI. Reduced autobiographical episodic memories in aMCI may be the result of medial temporal lobe dysfunction, consistent with multiple trace theory, or alternatively, could be related to dysfunction of a wider related network of neocortical structures. In contrast, the preservation of autobiographical semantic memories in aMCI suggests neural systems, such as lateral temporal cortex, that support these memories, may remain relatively intact.

Mild cognitive impairment is associated with poorer decision-making in community-based older persons.

Science.gov (United States)

Han, S Duke; Boyle, Patricia A; James, Bryan D; Yu, Lei; Bennett, David A

2015-04-01

To test the hypothesis that mild cognitive impairment (MCI) is associated with poorer financial and healthcare decision-making. Community-based epidemiological cohort study. Communities throughout northeastern Illinois. Older persons without dementia from the Rush Memory and Aging Project (N = 730). All participants underwent a detailed clinical evaluation and decision-making assessment using a measure that closely approximates materials used in real-world financial and healthcare settings. This allowed for measurement of total decision-making and financial and healthcare decision-making. Regression models were used to examine whether MCI was associated with a lower level of decision-making. In subsequent analyses, the relationship between specific cognitive systems (episodic memory, semantic memory, working memory, perceptual speed, visuospatial ability) and decision-making was explored in participants with MCI. MCI was associated with lower total, financial, and healthcare decision-making scores after accounting for the effects of age, education, and sex. The effect of MCI on total decision-making was equivalent to the effect of more than 10 additional years of age. Additional models showed that, when considering multiple cognitive systems, perceptual speed accounted for the most variance in decision-making in participants with MCI. Persons with MCI may have poorer financial and healthcare decision-making in real-world situations, and perceptual speed may be an important contributor to poorer decision-making in persons with MCI. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.