431 research outputs found
Decoding the Encoding of Functional Brain Networks: an fMRI Classification Comparison of Non-negative Matrix Factorization (NMF), Independent Component Analysis (ICA), and Sparse Coding Algorithms
Brain networks in fMRI are typically identified using spatial independent
component analysis (ICA), yet mathematical constraints such as sparse coding
and positivity both provide alternate biologically-plausible frameworks for
generating brain networks. Non-negative Matrix Factorization (NMF) would
suppress negative BOLD signal by enforcing positivity. Spatial sparse coding
algorithms ( Regularized Learning and K-SVD) would impose local
specialization and a discouragement of multitasking, where the total observed
activity in a single voxel originates from a restricted number of possible
brain networks.
The assumptions of independence, positivity, and sparsity to encode
task-related brain networks are compared; the resulting brain networks for
different constraints are used as basis functions to encode the observed
functional activity at a given time point. These encodings are decoded using
machine learning to compare both the algorithms and their assumptions, using
the time series weights to predict whether a subject is viewing a video,
listening to an audio cue, or at rest, in 304 fMRI scans from 51 subjects.
For classifying cognitive activity, the sparse coding algorithm of
Regularized Learning consistently outperformed 4 variations of ICA across
different numbers of networks and noise levels (p0.001). The NMF algorithms,
which suppressed negative BOLD signal, had the poorest accuracy. Within each
algorithm, encodings using sparser spatial networks (containing more
zero-valued voxels) had higher classification accuracy (p0.001). The success
of sparse coding algorithms may suggest that algorithms which enforce sparse
coding, discourage multitasking, and promote local specialization may capture
better the underlying source processes than those which allow inexhaustible
local processes such as ICA
Automatic Look-Up Table Based Real-Time Phase Unwrapping for Phase Measuring Profilometry and Optimal Reference Frequency Selection
For temporal phase unwrapping in phase measuring profilometry, it has recently been reported that two phases with co-prime frequencies can be absolutely unwrapped using a look-up table; however, frequency selection and table construction has been performed manually without optimization. In this paper, a universal phase unwrapping method is proposed to unwrap phase flexibly and automatically by using geometric analysis, and thus we can programmatically build a one-dimensional or two-dimensional look-up table for arbitrary two co-prime frequencies to correctly unwrap phases in real time. Moreover, a phase error model related to the defocus effect is derived to figure out an optimal reference frequency co-prime to the principal frequency. Experimental results verify the correctness and computational efficiency of the proposed method
Universal Phase Unwrapping for Phase Measuring Profilometry Using Geometry Analysis
Traditionally temporal phase unwrapping for phase measuring profilometry needs to employ the phase computed from unit-frequency patterned images; however, it has recently been reported that two phases with co-prime frequencies can be absolutely unwrapped each other. However, a manually man-made look-up table for two known frequencies has to be used for correctly unwrapping phases. If two co-prime frequencies are changed, the look-up table has to be manually rebuilt. In this paper, a universal phase unwrapping algorithm is proposed to unwrap phase flexibly and automatically. The basis of the proposed algorithm is converting a signal-processing problem into a geometric analysis one. First, we normalize two wrapped phases such that they are of the same needed slope. Second, by using the modular operation, we unify the integer-valued difference of the two normalized phases over each wrapping interval. Third, by analyzing the properties of the uniform difference mathematically, we can automatically build a look-up table to record the corresponding correct orders for all wrapping intervals. Even if the frequencies are changed, the look-up table will be automatically updated for the latest involved frequencies. Finally, with the order information stored in the look-up table, the wrapped phases can be correctly unwrapped. Both simulations and experimental results verify the correctness of the proposed algorithm
Evaluation of NAD(H) analogues as selective inhibitors for Trypanosoma cruzi S-Adenosylhomocysteine hydrolase
This is an Accepted Manuscript of an article published by Taylor & Francis in Nucleosides, Nucleotides and Nucleic Acids in May 2009, available online: http://www.tandfonline.com/10.1080/15257770903044572.S-Adenosylhomocysteine (AdoHcy) hydrolases (SAHHs) from human sources (Hs-SAHHs) bind the cofactor NAD+ more tightly than several parasitic SAHHs by around 1000-fold. This property suggests the cofactor binding site of this essential enzyme as a potential anti-parasitic drug target, e.g., against SAHH from Trypansoma cruzi (Tc-SAHH). The on-rate and off-rate constants and the equilibrium dissociation constants were determined for NAD+/NADH analogues and suggested that NADH analogues were the most promising for selective inhibition of Tc-SAHH. None significantly inhibited Hs-SAHH while S-NADH and H-NADH (Fig. 1) reduced the catalytic activity of Tc-SAHH to <10% in six minutes of exposure
The Rationale for Targeting the NAD/NADH Cofactor Binding Site of Parasitic S-Adenosyl-L-homocysteine Hydrolase for the Design of Anti-parasitic Drugs
This is an Accepted Manuscript of an article published by Taylor & Francis in Nucleosides, Nucleotides and Nucleic Acids in May 2009, available online: http://www.tandfonline.com/10.1080/15257770903051031.Trypanosomal S-adenoyl-L-homocysteine hydrolase (Tc-SAHH), considered as a target for treatment of Chagas disease, has the same catalytic mechanism as human SAHH (Hs-SAHH) and both enzymes have very similar X-ray structures. Efforts toward the design of selective inhibitors against Tc-SAHH targeting the substrate binding site have not to date shown any significant promise. Systematic kinetic and thermodynamic studies on association and dissociation of cofactor NAD/H for Tc-SAHH and Hs-SAHH provide a rationale for the design of anti-parasitic drugs directed toward cofactor-binding sites. Analogues of NAD and their reduced forms show significant selective inactivation of Tc-SAHH, confirming that this design approach is rational
Comparative Kinetics of Cofactor Association and Dissociation for the Human and Trypanosomal S-Adenosylhomocysteine Hydrolases. 3. Role of Lysyl and Tyrosyl Residues of the C-Terminal Extension
Based on the available X-ray structures of S-adenosylhomocysteine hydrolases (SAHHs), free energy simulations employing the MM-GBSA approach were applied to predict residues important to the differential cofactor binding properties of human and trypanosomal SAHHs (Hs-SAHH and Tc-SAHH), within 5 Å of the cofactor NAD+/NADH binding site. Among the 38 residues in this region, only four are different between the two enzymes. Surprisingly, the four non-identical residues make no major contribution to differential cofactor binding between Hs-SAHH and Tc-SAHH. On the other hand, four pairs of identical residues are shown by free energy simulations to differentiate cofactor binding between Hs-SAHH and Tc-SAHH. Experimental mutagenesis was performed to test these predictions for a lysine residue and a tyrosine residue of the C-terminal extension that penetrates a partner subunit to form part of the cofactor binding site. The K431A mutant of Tc-SAHH (TcK431A) loses its cofactor binding affinity but retains the wild type’s tetrameric structure, while the corresponding mutant of Hs-SAHH (HsK426A) loses both cofactor affinity and tetrameric structure (Ault-Riche et al., 1994 J Biol Chem, 269, 31472–8). The tyrosine mutants HsY430A and TcY435A alter the NAD+ association and dissociation kinetics, with HsY430A increasing the cofactor equilibrium dissociation constant from approximately 10 nM (Hs-SAHH) to about 800 nM while TcY435A increases the cofactor equilibrium dissociation constant from approximately 100 nM (Tc-SAHH) to about 1 mM. Both changes result from larger increases in off-rate combined with smaller decreases in on-rate. These investigations demonstrate that computational free energy decomposition may be used to guide experimental studies by suggesting sensitive sites for mutagenesis. Our finding that identical residues in two orthologous proteins may give significantly different binding free energy contributions strongly suggests that comparative studies of homologous proteins should investigate not only different residues, but also identical residues in these proteins
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Moderate-vigorous physical activity and health-related quality of life among Hispanic/Latino adults in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
BackgroundPhysical activity is a modifiable healthy behavior that has been shown to positively influence health-related quality of life. However, research examining the link between physical activity and health-related quality of life among Hispanic/Latino adults is limited and inconsistent. The purpose of this study is to assess whether accelerometer-measured moderate-vigorous physical activity (MVPA) is associated with self-reported (a) mental health-related quality of life, and (b) physical health-related quality of life among diverse Hispanic/Latino adults in the US.MethodsCross-sectional data from 12,379 adults ages 18-74 years in 2008-2011, who participated in HCHS/SOL and had complete data were analyzed using complex survey design methods. Accelerometer data were categorized into no MVPA, low, moderate, and high MVPA. Health-related quality of life was assessed with the Short-Form 12 and we used the mental and physical component subscales where higher scores indicate better health-related quality of life. Multivariate linear regression models were used to derive adjusted means with 95% confidence intervals and linear trends.ResultsWe observed no significant linear trend between accelerometer-measured MVPA and mental health-related quality of life (ptrend = 0.73). There was a significant positive association between MVPA and physical health-related quality of life (ptrend < 0.001) where higher MVPA corresponded with higher scores in physical health-related quality of life. The adjusted means were 46.67 (44.85-48.48) for no MVPA, 49.33 (49.03-49.63) for low MVPA, 50.61 (50.09-51.13) for moderate MVPA, and 51.36 (50.86-51.86) for high MVPA.ConclusionsAmong diverse Hispanic/Latino adults in the US, accelerometer-measured MVPA was associated with physical health-related quality of life, but not mental health-related quality of life. Future interventions should evaluate if increases in MVPA lead to improvements in health-related quality of life
Regression splines in the time-dependent coefficient rates model for recurrent event data
Many epidemiologic studies involve the occurrence of recurrent events and much attention has been given for the development of modelling techniques that take into account the dependence structure of multiple event data. This paper presents a time-dependent coefficient rates model that incorporates regression splines in its estimation procedure. Such method would be appropriate in situations where the effect of an exposure or covariates changes over time in recurrent event data settings. The finite sample properties of the estimators are studied via simulation. Using data from a randomized community trial that was designed to evaluate the effect of vitamin A supplementation on recurrent diarrheal episodes in small children, we model the functional form of the treatment effect on the time to the occurrence of diarrhea. The results describe how this effect varies over time. In summary, we observed a major impact of the vitamin A supplementation on diarrhea after 2 months of the dosage, with the effect diminishing after the third dosage. The proposed method can be viewed as a flexible alternative to the marginal rates model with constant effect in situations where the effect of interest may vary over time
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