Werner syndrome (WS) is an autosomal recessive progeroid disorder caused by mutations in RecQ DNA helicase. Ectopic soft tissue calcification is one of the well known symptoms in WS. However, the prevalence, clinical outcome, and mechanism of such calcification remain to be elucidated. The clinical features and mechanism of ectopic calcification were examined in seven patients with WS whose diagnosis were confirmed by a genomic DNA analysis. X-ray examinations revealed subcutaneous calcification in 35 of 41 major joints (85.3%). The patients complained of dermal pain at 23 joints among 35 joints (65.7%) with calcification. Refractory skin ulcers were found at the area of the skin overlaying the calcification in 16 joints (45.7%). In contrast, no pain or ulcers were observed in the joints without calcification. The presence of ectopic calcification could not be explained by a systemic hormonal abnormality. Cultured fibroblasts from WS patients underwent spontaneous mineralization in vitro in the normal phosphate condition, and overexpressed Pit-1, a transmembrane type III Na-Pi cotransporter both at the mRNA and protein levels. Phosphonophormic acid, a specific inhibitor for Pit-1, inhibited mineralization in the WS fibroblasts. Both calcification and Pit-1 overexpression were detected in the skin of WS in situ. WS showed a high prevalence of ectopic calcification, which was associated with dermal pain and refractory skin ulcers. An overexpression of Pit-1 therefore seems to play a key role in the formation of soft tissue calcification in this syndrome.

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Equivalence structure (ES) extraction focuses on multidimensional temporal patterns that appear in a multidimensional sequence and in a different multidimensional sequence. The input of the task is a set of sequences and the output is a set of ESs. An ES is a set of K-tuples comprising elements of K IDs to specify K sequences, and it shows which K-dimensional sequences composed of K sequences specified by its K-tuples are considered equivalent. The standard for determining whether K-dimensional sequences are equivalent is based on the subsequences of the K-dimensional sequences. ES extraction can be used for multidimensional temporal feature extraction, as well as preprocessing for transfer learning or imitation learning. A method called ES incremental search (ESIS) was recently proposed, which is much faster than brute-force search, but the proofs necessary to derive it had not been sufficient. Therefore, it has been unclear why ESIS worked and can be reliable. This paper presents proofs to validate ESIS, as well as a property of the solution of ESIS that could be useful for developing a faster method.