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<i>BRCA2</i> Hypomorphic Missense Variants Confer Moderate Risks of Breast Cancer
Shimelis, Hermela,Mesman, Romy L.S.,Von Nicolai, Catharina,Ehlen, Asa,Guidugli, Lucia,Martin, Charlotte,Callé,ja, Fabienne M.G.R.,Meeks, Huong,Hallberg, Emily,Hinton, Jamie,Lilyquist, Jenna,Hu, American Association for Cancer Research 2017 Cancer Research Vol.77 No.11
<P>These results show how BRCA2 missense variants that partially influence protein function can confer clinically relevant increased risks of breast cancer, with potential implications for risk management of women who harbor specific variants.</P><P>Breast cancer risks conferred by many germline missense variants in the <I>BRCA1</I> and <I>BRCA2</I> genes, often referred to as variants of uncertain significance (VUS), have not been established. In this study, associations between 19 BRCA1 and 33 BRCA2 missense substitution variants and breast cancer risk were investigated through a breast cancer case–control study using genotyping data from 38 studies of predominantly European ancestry (41,890 cases and 41,607 controls) and nine studies of Asian ancestry (6,269 cases and 6,624 controls). The BRCA2 c.9104A>C, p.Tyr3035Ser (OR = 2.52; <I>P</I> = 0.04), and BRCA1 c.5096G>A, p.Arg1699Gln (OR = 4.29; <I>P</I> = 0.009) variant were associated with moderately increased risks of breast cancer among Europeans, whereas BRCA2 c.7522G>A, p.Gly2508Ser (OR = 2.68; <I>P</I> = 0.004), and c.8187G>T, p.Lys2729Asn (OR = 1.4; <I>P</I> = 0.004) were associated with moderate and low risks of breast cancer among Asians. Functional characterization of the BRCA2 variants using four quantitative assays showed reduced BRCA2 activity for p.Tyr3035Ser compared with wild-type. Overall, our results show how BRCA2 missense variants that influence protein function can confer clinically relevant, moderately increased risks of breast cancer, with potential implications for risk management guidelines in women with these specific variants. <I>Cancer Res; 77(11); 2789–99. ©2017 AACR</I>.</P>
Fabrication of high density pellets of ZrO2 via particle processing
Thomas T. Meek 한양대학교 세라믹연구소 2013 Journal of Ceramic Processing Research Vol.14 No.1
Fabrication of oxide nuclear fuels has generally been unsuccessful due to the instability of fuel loss of americium oxide during the high temperature sintering process. A low temperature-processing route that enables near net shapes in almost theoretical density is highly desirable. In order to carry out low-temperature processing, it is necessary to design oxide blends with controlled particle sizes. A compact made of the right mix of particles can be pressed at room temperature to near theoretical density. Powders have been blended to form multimodal distributions. It should be possible to use these blends to isostatically press samples with fractional densities of greater than 85% at room temperature.
An Evaluation of Assessing the Functional Movement Screen™ from Video Playback
Matthew D Portas,Daniel Meek,Warren Gregson,Barry Drust 한국코칭능력개발원 2015 International Journal of Coaching Science Vol.9 No.2
The study aimed to evaluate the method comparison and intra-rater test-retest reliability of the Functional Movement Screen when assessed by real-time and video playback. Eighteen participants (Age: 22 ± 2 years, Height: 1.77 m ± 0.10 m, Weight: 78.2 ± 11.5 kg, 15 males and 3 females), participated. Participants were scored during the screen in real-time by an experienced coach. Each screen was also video recorded in the frontal and sagittal plane. The coach then scored each FMS via video, in a randomised order, 3 days (video-1) and 7 days later (video-2). Median and interquartile range were calculated for the group score in each assessment. The weighted kappa statistic, percentage of agreement and bias were then calculated for each FMS test.. The median (interquartile ranges) for the group FMS score was 16.0 (15.0 and 17.0) for the live assessment; 16 (14.0 and 17.0) for video-1 and 16 (13.8 and 17.0) for video-2. The mean (SD) agreement across all tests live compared to video was 87.4% (11.1) with a weighted kappa statistic of 0.9 (0.1) (almost perfect). These results provide guidance for the interchangeably of these techniques in practice and confirm the legitimacy of the approach for the previous work that used video to assess reliability of measurement.
Ik Mo Lee,Devon W. Meek,Judith Gallucci Korean Chemical Society 1992 Bulletin of the Korean Chemical Society Vol.13 No.5
The protonation of RuH(NO)(Cyttp) resulted in the formation of $[RuH_2(NO)(Cyttp)]^+$ which is characterized as a classical cis-dihydried complex. This complex is fluxional and the intramolecular process involving a molecular hydrogen complex is proposed. This mechanism was further supported by the reactivity of this complex toward neutral 2-electron ligands. On the other hand, it failed to detect the existence of $[RuH_2(NO)(etp)]^+$ probably due to instability of the complex but the crystal structure of $[Ru(PMe_3)(NO)(etp)]^+$ formed by the protonation of RuH(NO)(etp) followed by the addition of $PMe_3$ was determined to have a trigonal bipyramidal structure with a linear NO in the equatorial plane and a facial etp ligand. The crystals are monoclinic, space group P21/n, with unit cell dimensions a = 14.130(2), b = 21.026 (3), c = 14.760 (1) ${\AA}$, ${\beta}$ = 97.88 $(l)^{\circ}$ V = 4344 ${\AA}^3$, Z = 4, R = 0.046 and $R_w$ = 0.056 for the 4779 intensities with $F_o^2 > 3{\sigma}(F_0^2)$ and the 440 variables.
Ik Mo Lee,Yeoug Joong Kim,Ook Jae Cho,Devon W. Meek Korean Chemical Society 1992 Bulletin of the Korean Chemical Society Vol.13 No.5
fac-RuH(NO)(ttp) is fluxional in the range between 180 K and 303 K. The structures involved in this fluxional process are found to be a mixture of two square pyramids and a trigonal bipyramid from the low temperature NMR spectra and the line shape analysis using DNMR 3 program and the activation parameters of this process were determined by using the simulated data. The mechanism of this fluxional process is proposed to be a pathway known as Turnstile Rotation.
Ik-Mo Lee,Ook-Jae Cho,Devon W. Meek,Chan-Yong Kim Korean Chemical Society 1993 Bulletin of the Korean Chemical Society Vol.14 No.5
The types of the products of the reactions between RuH(NO)(Cyttp) and alkynes are sensitive to the nature of alkynes. Terminal, nonactivated alkynes (HC${\equiv}$CR, R=Ph, hexyl and $CH_2OH)$ produce acetylide complexes and terminal (HC${\equiv}$CR, R=C(O)Me, COOEt) or internal activated ones (RC${\equiv}$ CR, R=COOMe) lead to form alkenyl complexes. On the other hand, internal nonactivated alkynes (RC${\equiv}$CR, R=Ph) do not show reactivity toward RuH(NO)(Cyttp). These products can be rationalized by the cis-concerted mechanism but the radical pathway appears to work in the reaction of propargyl chloride. From the spectroscopic data, the trigonal bipyramidal structure with a linear NO group is proposed for these products.