Increased acinar damage of salivary glands of patients with Sjögren's syndrome is paralleled by simultaneous imbalance of matrix metalloproteinase 3/tissue inhibitor of metalloproteinases 1 and matrix metalloproteinase 9/tissue inhibitor of metalloproteinases 1 ratios

Indexación: Scopus.Objective. Previous findings in labial salivary glands (LSGs) from patients with Sjögren's syndrome (SS) suggest that increased activity and expression of matrix metalloproieinase 9 (MMP-9) and MMP-3 trigger the destruction of acinar structures in these glands. Tissue inhibitors of matrix metalloproteinases (TIMPs) tightly control MMP activity, and TIMP expression is an important modulator of effects attributed to MMPs. This study was undertaken to investigate the correlation between the balance of MMPs/TIMPs in the LSGs of SS patients and the degree of inflammatory infiltration and acinar structure integrity. Methods. Three groups of SS patients classified according to focus score and residual tissue were studied. The expression of MMP-2, MMP-3, MMP-9, TIMP-1, and TIMP-2 was examined at the messenger RNA and protein levels. The ratio of MMP/TIMP expression (R value) was calculated. Focus score and acinar structure were evaluated by histologic analysis. Results. In SS patients the MMP-3/TIMP-1 ratio was higher than 1 and the MMP-9/TIMP-1 ratio was much higher than 1 whereas the MMP-2/TIMP-2 ratio nearly equaled 1, suggesting elevated proteolytic activity due mainly to MMP-9. R values were independent of the focus score of inflammatory cells, but correlated well with the dramatic changes observed in morphologic integrity of acini, as revealed mainly by the lack of nuclear polarity. Acinar changes were more evident when R values for both MMP-9/TIMP-1 and MMP-3/TIMP-1 were higher. Conclusion. This study provides evidence that an altered balance between MMPs and their inhibitors is associated with acinar damage. Since salivary gland acinar cells express both MMPs and TIMPs, these cells may play an important role in extracellular matrix destruction and in the LSG pathophysiology in SS.https://onlinelibrary.wiley.com/doi/full/10.1002/art.2126

Parallelisation and application of AD3 as a method for solving large scale combinatorial auctions

Auctions, and combinatorial auctions (CAs), have been successfully employed to solve coordination problems in a wide range of application domains. However, the scale of CAs that can be optimally solved is small because of the complexity of the winner determination problem (WDP), namely of finding the bids that maximise the auctioneer’s revenue. A way of approximating the solution of a WDP is to solve its linear programming relaxation. The recently proposed Alternate Direction Dual Decomposition algorithm (AD3) has been shown to ef- ficiently solve large-scale LP relaxations. Hence, in this paper we show how to encode the WDP so that it can be approximated by means of AD3. Moreover, we present PAR-AD3, the first parallel implementation of AD3. PAR-AD3 shows to be up to 12.4 times faster than CPLEX in a single-thread execution, and up to 23 times faster than parallel CPLEX in an 8-core architecture. Therefore PAR- AD3 becomes the algorithm of choice to solve large-scale WDP LP relaxations for hard instances. Furthermore, PAR-AD3 has potential when considering large- scale coordination problems that must be solved as optimisation problems.Research supported by MICINN projects TIN2011-28689-C02-01, TIN2013-45732-C4-4-P and TIN2012-38876-C02-01Peer reviewe

Dopamine precursor depletion improves punishment prediction during reversal learning in healthy females but not males

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Logopenic and nonfluent variants of primary progressive aphasia are differentiated by acoustic measures of speech production

Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r2 = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA

Comparison of self-assessment and objective indicators of attributes driving farms resilience

PRIMA project Adapt-Her