A multidisciplinary design optimization (MDO) process of a large scale hybrid composite wind turbine blade is developed. Multiple objectives are considered in this design optimization: maximize length of blade, minimize weight and manufacturing cost. A wind turbine blade is divided into regions and the layup sequences for each region are considered as design variables. Applied load due to extreme wind condition for rotor rotation and rotor stop condition are considered for finite element analysis (FEA) to evaluate the structural strength. The structural stiffness is designed and illustrated so that the natural frequency of the blade does not coincidence with the excitation frequency of the wind turbine. A process of obtaining an optimum hybrid composite laminate layup and an optimum length of wind turbine blade is developed in this research.

Human Bax Inhibitor‐1 (HsBI‐1/TMBIM6) is the founding member of the evolutionary conserved TMBIM superfamily of proteins that share sequence homology within the transmembrane Bax inhibitor‐containing motif (TMBIM). Mechanistically, BI‐1/TMBIM6 and all the other mammalian TMBIM proteins appear to be involved in the maintenance of calcium homeostasis, and the crystal structure of a bacterial TMBIM protein, BsYetJ, suggests that the protein is a pH‐sensitive calcium leak. The budding yeast, Saccharomyces cerevisiae, has a single TMBIM family member (YNL305C) named Bxi1p/Ybh3p. To determine the function of Bxi1p/Ybh3p, we overexpressed Bxi1p‐EGFP in E. coli to determine if it is a calcium channel. We show that bacterial cells expressing Bxi1p‐EGFP are more permeable to calcium than controls. Thus, our data suggests that yeast Bax inhibitor (Bxi1p) is a calcium channel in E. coli, lending support to our proposal that Bxi1p is a bona fide member of the TMBIM family of proteins. Further, we use our bacterial system to show that gadolinium is an inhibitor of Bxi1p in vivo, suggesting a path forward to identifying other small‐molecular inhibitors of this clinically‐important and highly conserved superfamily of proteins. Finally, parallel experiments revealed that the human Bax Inhibitor‐1 (HsBI‐1/TMBIM6) is also a calcium channel in bacteria that can be inhibited by gadolinium. Support or Funding Information Our laboratory is supported by grant NIGMS R15 GM110578, awarded to N. Austriaco.

Human Bax Inhibitor‐1 (HsBI‐1/TMBIM6) is the founding member of the evolutionary conserved TMBIM superfamily of proteins that share sequence homology within the transmembrane Bax inhibitor‐containing motif (TMBIM). Mechanistically, BI‐1/TMBIM6 and all the other mammalian TMBIM proteins appear to be involved in the maintenance of calcium homeostasis, and the crystal structure of a bacterial TMBIM protein, BsYetJ, suggests that the protein is a pH‐sensitive calcium leak. The budding yeast, Saccharomyces cerevisiae, has a single TMBIM family member (YNL305C) named Bxi1p/Ybh3p. To determine the function Bxi1p/Ybh3p, we overexpressed Bxi1p‐GFP in E. coli to interrogate its putative calcium channel function. We show that bacterial cells expressing Bxi1p‐GFP are more permeable to calcium than controls. Our data suggests that yeast Bax inhibitor (Bxi1p) is a calcium channel in E. coli, lending support to our proposal that Bxi1p is a bona fide member of the TMBIM family of proteins. We use our bacterial system to show that gadolinium is an inhibitor of Bxi1p in vivo, suggesting a path forward to identifying other small‐molecular inhibitors of this clinically‐important and highly conserved superfamily of proteins. Finally, parallel experiments revealed that the human Bax Inhibitor‐1 (HsBI‐1/TMBIM6) is also a calcium channel in bacteria that can be inhibited by gadolinium.

21Human Bax Inhibitor-1 (HsBI-1/TMBIM6) is the founding member of the evolutionary 22 conserved TMBIM superfamily of proteins that share sequence homology within the 23 transmembrane Bax inhibitor-containing motif (TMBIM). Mechanistically, BI-1/TMBIM6 and 24 all the other mammalian TMBIM proteins appear to be involved in the maintenance of calcium 25 homeostasis, and the crystal structure of a bacterial TMBIM protein, BsYetJ, suggests that the 26 protein is a pH-sensitive calcium leak. The budding yeast, Saccharomyces cerevisiae, has a single 27 TMBIM family member (YNL305C) named Bxi1p/Ybh3p. To determine the function of 28Bxi1p/Ybh3p, we overexpressed Bxi1p-EGFP in E. coli to determine if it is a calcium channel. We 29show that bacterial cells expressing Bxi1p-EGFP are more permeable to calcium than controls. 30Thus, our data suggests that yeast Bax inhibitor (Bxi1p) is a calcium channel in E. coli, lending 31 support to our proposal that Bxi1p is a bona fide member of the TMBIM family of proteins. 32Further, we use our bacterial system to show that gadolinium is an inhibitor of Bxi1p in vivo, 33 suggesting a path forward to identifying other small-molecular inhibitors of this clinically-34 important and highly conserved superfamily of proteins. Finally, parallel experiments revealed 35 that the human Bax Inhibitor-1 (HsBI-1/TMBIM6) is also a calcium channel in bacteria that can 36 be inhibited by gadolinium. 37

Yeast Bax Inhibitor‐1 (BXI1/YBH3) encodes a protein (Bxi1p) that belongs to the Bax Inhibitor family of proteins. In mammals, this family of proteins has cytoprotective properties that are most evident in paradigms of endoplasmic reticulum (ER) stress and have been linked to several human cancers. Both the crystal structure of a prokaryotic member of the family (BsYetJ) and our own published studies suggest that yeast Bxi1p is a pH‐sensitive calcium leak channel localized to the ER membrane. It is involved in the unfolded protein response (UPR). Bxi1p is thought to act via a mechanism involving altered calcium dynamics. We now show that cells lacking BXI1 have an altered redox microenvironment in the ER. We also report that cells lacking BXI1 accumulate more calcium in the ER than wild type cells. Together, our data suggest that Bxi1p is involved in regulating the ER microenvironment and, consequently, programmed cell death.Support or Funding InformationOur laboratory is supported by grant NIGMS R15 GM110578, awarded to N. Austriaco.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.