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ROIs were defined on the basis of the segmented MRI and a probabilistic template as implemented in PVElab [25].
ROIs were defined on the segmented MRI using a probabilistic template as implemented in the PVElab software [33].
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Regions were identified by using the AAL atlas (Tzourio-Mazoyer et al. 2002) and Brodmann templates as implemented in MRIcron (www.cabiatl.com/mricro/mricron).
A volume-of-interest template [15] as implemented in PMOD (PMOD Technologies Ltd ,Zurich, Switzerland) was used to obtain brain time-activity curves.
The preprocessing steps applied for this study were motion correction, spatial normalization to standard template and spatial smoothing as implemented in SPM5.
The crystal structure of a GH43 endo-arabinanase from Bacillus subtilis (PDB entry code: 2X8T) was used as three-dimensional template for restraint-based modeling as implemented in SPDBV_4.04_PC.
The RMSD of the TMH backbone atoms was calculated for each pair of template structures using the McLachlan algorithm [69] as implemented in the program ProFit (Martin, A.C.R., http://www.bioinf.org.uk/software/profit/).uk/software/profit/
This necessitated manual background subtraction as implemented in the Excel template used for LRE quantification (additional file 2).
Anatomic labels and Brodmann areas (BA) were identified using the Talairach atlas (Talairach and Tournoux 1988) and confirmed using the template developed by the van Essen lab as implemented in MRIcron (http://www.MRicro.com/MRicron).
The average intensity template generated from the final set of registrations is shown in Figure 1 A. Voxelwise cross-subject statistical analysis of volume relative to the template, represented by the Jacobian, was performed with Randomise (v2.5) as implemented in FMRIB's Software Library (Smith et al. 2004) (FSL v4.1; www.fmrib.ox.ac.uk/fsl).ac.uk/fsl
The transformation of each participant to the spiral template was achieved using a 12-parameter affine transform with sinc interpolation as implemented in SPM99 (http://www.fil.ion.ucl.ac.uk/spm/, Friston et al. 1995).
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