Prioritizing MCDC test cases by spectral analysis of Boolean functions

Test case prioritization aims at scheduling test cases in an order that improves some performance goal. One performance goal is a measure of how quickly faults are detected. Such prioritization can be performed by exploiting the Fault Exposing Potential (FEP) parameters associated to the test cases. FEP is usually approximated by mutation analysis under certain fault assumptions. Although this technique is effective, it could be relatively expensive compared to the other prioritization techniques. This study proposes a cost-effective FEP approximation for prioritizing Modified Condition Decision Coverage (MCDC) test cases. A strict negative correlation between the FEP of a MCDC test case and the influence value of the associated input condition allows to order the test cases easily without the need of an extensive mutation analysis. The method is entirely based on mathematics and it provides useful insight into how spectral analysis of Boolean functions can benefit software testing

miR-335ではなくMestは骨格筋の成長と再生に影響を与える

京都大学0048新制・課程博士博士(医学)甲第19271号医博第4035号新制||医||1011(附属図書館)32273京都大学大学院医学研究科医学専攻(主査)教授 妻木 範行, 教授 松田 秀一, 教授 萩原 正敏学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

Identification of SMCHD1 domains for nuclear localization, homo-dimerization, and protein cleavage

Abstract Background SMCHD1 is a disease modifier and a causative gene for facioscapulohumeral muscular dystrophy (FSHD) type 1 and type 2, respectively. A large variety of different mutations in SMCHD1 have been identified as causing FSHD2. In many cases, it is unclear how these mutations disrupt the normal function of SMCHD1. Methods We made and analyzed lenti-viral vectors that express Flag-tagged full-length or different mutant SMCHD1 proteins to better understand the functional domains of SMCHD1 in muscle cells. Results We identified regions necessary for nuclear localization, dimerization, and cleavage sites. Moreover, we confirmed that some mutants increased DUX4 expression in FSHD1 myoblasts. Conclusions These findings provide an additional basis for understanding the molecular consequences of SMCHD1 mutations

Additional file 1: of Identification of SMCHD1 domains for nuclear localization, homo-dimerization, and protein cleavage

Sequences of the primers for constructions. (XLSX 23 kb

Additional file 2: of Identification of SMCHD1 domains for nuclear localization, homo-dimerization, and protein cleavage

Sequences of the primers for RT-qPCR. (XLSX 46 kb

<i>Mest</i> and miR-335 are coordinately expressed in skeletal muscle during postnatal development and regeneration.

<p>(A) qRT-PCRs for <i>Mest</i> mRNA and miR-335 were performed with TA muscles of P0, 6 weeks, and 12 weeks old WT mice (n = 3 per time point). (B) qRT-PCRs for <i>Mest</i> mRNA and miR-335 were performed with TA muscles of 3 months old WT (n = 4) and <i>DMD–null</i> mice (n = 7). (C) qRT-PCRs for <i>Mest</i> mRNA and miR-335 were performed with TA muscles from day 0 to day 10 after CTX injection (n = 3 per time point). (D) A schematic diagram of the Mest and miR-335 genomic region on chromosome 6 in mouse. (E) qRT-PCR for miR-335 was performed in TA muscles of WT and <i>Mest</i>^<i>+/-</i> mice (n = 3 per genotype). Expression of <i>Mest</i> and that of miR-335 are normalized to <i>Gapdh</i> and snoRNA-202, respectively. Error bars indicate the s.e.m. *<i>P</i> < 0.05, **<i>P</i> < 0.01, ***<i>P</i> < 0.001 compared with P0 (A), WT (B and E), and day 0 (C).</p

Mest but Not MiR-335 Affects Skeletal Muscle Growth and Regeneration

<div><p>When skeletal muscle fibers are injured, they regenerate and grow until their sizes are adjusted to surrounding muscle fibers and other relevant organs. In this study, we examined whether <i>Mest</i>, one of paternally expressed imprinted genes that regulates body size during development, and miR-335 located in the second intron of the <i>Mest</i> gene play roles in muscle regeneration. We generated miR-335-deficient mice, and found that miR-335 is a paternally expressed imprinted microRNA. Although both <i>Mest</i> and miR-335 are highly expressed during muscle development and regeneration, only <i>Mest^+/-</i> (maternal/paternal) mice show retardation of body growth. In addition to reduced body weight in <i>Mest^+/-; DMD-null</i> mice, decreased muscle growth was observed in <i>Mest^+/-</i> mice during cardiotoxin-induced regeneration, suggesting roles of Mest in muscle regeneration. Moreover, expressions of <i>H19</i> and <i>Igf2r</i>, maternally expressed imprinted genes were affected in tibialis anterior muscle of <i>Mest^+/-; DMD-null</i> mice compared to <i>DMD-null</i> mice. Thus, Mest likely mediates muscle regeneration through regulation of imprinted gene networks in skeletal muscle.</p></div

Mest is required for body and skeletal muscle growth.

<p>(A) Representative images of 4 weeks old mice in individual genotypes. (B and C) Body weights of male littermate WT (n = 3–22), <i>Mest</i>^<i>+/-</i> (n = 6–15), <i>DMD-null</i> (n = 4–25), and <i>Mest</i>^<i>+/-</i><i>; DMD-null</i> mice (n = 4–22) from 1 to 12 (11–13) weeks old. (D) Body weights of WT (n = 15) and <i>miR-335</i>^<i>+/Neo</i> (n = 12) mice at 6 weeks. (E) Body weights of WT (n = 8–15) and <i>miR-335</i>^<i>+/-</i> mice (n = 15–18) from 1 to 6 weeks old. (F) TA muscle weights of male littermate WT (n = 13), <i>Mest</i>^<i>+/-</i> (n = 6), <i>DMD-null</i> (n = 18), and <i>Mest</i>^<i>+/-</i><i>; DMD-null</i> mice (n = 11) at 6 weeks old. (G) TA/Body weights of male littermate WT, <i>Mest</i>^<i>+/-</i>, <i>DMD-null</i>, and <i>Mest</i>^<i>+/-</i><i>; DMD-null</i> mice at 6 weeks old. (H) TA muscle weights of male littermate WT (n = 3), <i>Mest</i>^<i>+/-</i> (n = 6), <i>DMD-null</i> (n = 4), and <i>Mest</i>^<i>+/-</i><i>; DMD-null</i> mice (n = 4) at 11–13 weeks old. (I) TA/Body weights of male littermate WT, <i>Mest</i>^<i>+/-</i>, <i>DMD-null</i>, and <i>Mest</i>^<i>+/-</i><i>; DMD-null</i> mice at 11–13 weeks old. (J and K) The numbers and average cross section areas of TA muscle fibers of male littermate WT (n = 7) and <i>Mest</i>^<i>+/-</i> mice (n = 4) at 6 weeks. Error bars indicate the s.e.m. *<i>P</i> < 0.05, ***<i>P</i> < 0.001. NS = Not significant.</p

Mest is required for skeletal muscle growth during regeneration.

<p>(A) H&E staining of TA muscles under normal condition (top panel) and 14 days after CTX-induced injury (middle and bottom panels). Bottom panel shows the extended images of a part of middle panel. (B) Average cross section areas of TA muscles in WT (n = 3), <i>Mest</i>^<i>+/-</i> (n = 4) and <i>miR-335</i>^<i>+/Neo</i> mice (n = 6) under normal condition and WT (n = 7), <i>Mest</i>^<i>+/-</i> (n = 4) and <i>miR-335</i>^<i>+/Neo</i> mice (n = 6) 14 days after CTX injury. (C) H&E staining of TA muscles of <i>DMD-null</i>, <i>Mest</i>^<i>+/-</i><i>; DMD-null</i> and <i>miR-335</i>^<i>+/Neo</i><i>; DMD-null</i> mice at 11–13 weeks old. (D) Average cross section areas of TA muscles in <i>DMD-null</i> (n = 8), <i>Mest</i>^<i>+/-</i><i>; DMD-null</i> (n = 4) and <i>miR-335</i>^<i>+/Neo</i><i>; DMD-null</i> mice (n = 4) at 11–13 weeks old. Error bars indicate the s.e.m. ^<i>#</i><i>P</i> = 0.0549 compared with WT mice. Scale bar: 100 μm.</p