Partial correlation coefficients between muscle strength and muscle mass.

<p>Adjusted by age.</p><p>*: p<0.05,</p><p>**: p<0.01.</p><p>Partial correlation coefficients between muscle strength and muscle mass.</p

Relationships of age with knee extension strength and appendicular muscle mass in men.

<p>Relationships of age with knee extension strength and appendicular muscle mass in men.</p

Partial correlation coefficients between maximum walking speed, and muscle strength and muscle mass.

<p>Adjusted by age and height and weight.</p><p>*: p<0.05,</p><p>**: p<0.01.</p><p>Partial correlation coefficients between maximum walking speed, and muscle strength and muscle mass.</p

Knockdown of the genes decreased hypoxia/normoxia growth ratio due to increased growth during normoxia.

<p><b>A–C</b>, Confirmatory analysis of the oxygen-sensitive genes was performed as described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0035590#pone-0035590-g002" target="_blank">Figure 2</a>. The resulting hypoxia/normoxia growth ratio (<b>A</b>) and cell numbers when cultured during normoxia (<b>B</b>) or hypoxia (<b>C</b>) were analyzed. In <b>A–C</b>, error bars indicate s.d. (n = 3) and the data were analyzed by the t-test. *<i>p</i><0.05, **<i>p</i><0.01.</p

Gene ontology analysis of the identified oxygen-sensitive growth regulator genes.

<p>Categories of biological processes and molecular functions represented by at least two genes are listed.</p

Genome-wide shRNA screen for genes that regulate growth in an oxygen-dependent manner.

<p><b>A</b>, Scheme of the genome-wide shRNA screen. Cells transduced with the shRNA library were cultured under normoxia or hypoxia until the tenth passage. The shRNA target sequences were then amplified following reverse transcription PCR (RT-PCR) of total cellular RNA prepared from the selected transfectant pools. The identity and relative abundance of the biotin-labeled shRNA target sequences were evaluated by microarray. <b>B</b>, Array analysis of shRNA target sequences amplified from RNA prepared from cells cultured under normoxic or hypoxic selection. Genes targeted by four or more independent shRNA sequences, and which exhibited a representation that differed by more than 5-fold between cells grown under hypoxic and normoxic conditions represent candidate genes that modulate growth in response to the availability of oxygen and were studied further.</p

Identification of oxygen-sensitive genes with increased hypoxia/normoxia growth ratio when knocked-down.

<p><b>A–C</b>, Confirmatory analysis oxygen-sensitivity of genes indentified in the genome-wide screen. PC8 cells were transduced with lentiviral vectors expressing two independent shRNAs targeting each candidate gene and cultured for one week under normoxia or hypoxia. The resulting hypoxia/normoxia growth ratio (<b>A</b>) and cells numbers when cultured during normoxia (<b>B</b>) or hypoxia (<b>C</b>) were analyzed. In <b>A–C</b>, error bars indicate s.d. (n = 3) and the data were analyzed by the t-test. *<i>p</i><0.05, **<i>p</i><0.01.</p

A Complete Gear System in <i>N</i>‑Benzoyl-Carbazole Derivatives

2′,6′-Disubstituted <i>N</i>-benzoylated carbazole derivatives were found to exhibit atropisomerism. The bulky substituents restricted rotation about the N–C7′ and C7′–C1′ bonds to separate four atropisomers, in which rotation about the C7′–C1′ bond was in perfect concert with rotation about the N–C7′ bond. Complete geared rotation without slippage at 37 °C for 7 days was observed for the first time. Conformational analysis clarified the preference for the gear system over other internal conversion pathways

Elucidation of the <i>E-</i>Amide Preference of <i>N</i>‑Acyl Azoles

The conformational properties of <i>N</i>-acyl azoles (imidazole, pyrazole, and triazole) were examined. The <i>N</i>-2′,4′,6′-trichlorobenzoyl azoles were stable in methanol at room temperature, and no hydrolyzed products were observed over 7 days in the presence of 5% trifluoroacetic acid or 5% triethylamine in CDCl₃. The high stability may be explained by the double-bond amide character caused by the steric hindrance due to the <i>ortho</i>-substituents in the benzoyl group. While specific <i>E</i>-amide preferences were observed in <i>N</i>-acyl pyrazoles/triazoles, the amides of the imidazoles gave a mixture of <i>E</i> and <i>Z</i>. One of the conceivable ideas to rationalize this conformational preference may be repulsive interaction between two sets of lone-pair electrons on the pyrazole 2-nitrogen (n_N) and the carbonyl oxygen atoms (n_O) in the <i>Z</i>-conformation of <i>N</i>-acyl pyrazoles/triazoles. However, analysis of orbital interactions suggested that in the case of the <i>E</i>-conformation of <i>N</i>-acyl pyrazoles, such electron repulsion is small because of distance. The interbond energy calculations suggested that the <i>Z</i>-conformer is involved in strong vicinal σ–σ repulsion along the amide linkage between the σ_N1N2 and σ_C1C2 orbitals in the <i>anti</i>-periplanar arrangement and between the σ_N1C5 and σ_C1C2 orbitals in the <i>syn</i>-periplanar arrangement, which lead to the overwhelming <i>E</i>-preference in <i>N</i>-acyl pyrazoles/triazoles. In the case of <i>N</i>-acyl imidazoles, similar vicinal σ–σ repulsions were counterbalanced, leading to a weak preference for the <i>E</i>-conformer over the <i>Z</i>-conformer. The chemically stable and <i>E</i>-preferring <i>N</i>-acyl azoles may be utilized as scaffolds in future drug design

Changes in the proportion of Y93H RAV within each individual.

<p>The proportion of Y93H RAV over the Y93 wild type within each patient was determined by deep sequencing at baseline and at an early time point during SMV/PR therapy (within 7 days). The mean proportion of Y93H RAV was 52.7% at baseline and 29.7% during therapy (p = 0.023). The proportion of Y93H was reduced in 21 of 29 cases (72.4%, solid lines). In contrast, Y93H percentages increased in 8 cases (27.6%, broken lines).</p