Design Thinking-Informed Simulation: An Innovative Framework to Test, Evaluate, and Modify New Clinical Infrastructure.

Introduction: Designing new healthcare facilities is complex and transitions to new clinical environments carry high risks, as unanticipated problems may arise resulting in inefficient care and patient harm. Design thinking, a human-centered design method, represents a unique framework to support the planning, testing, and evaluation of new clinical spaces throughout all phases of construction. Healthcare simulation has been used to test new clinical spaces, yet most report using simulation only in the late design stages.

Bcl-XL inhibits membrane permeabilization by competing with Bax.

Although Bcl-XL and Bax are structurally similar, activated Bax forms large oligomers that permeabilize the outer mitochondrial membrane, thereby committing cells to apoptosis, whereas Bcl-XL inhibits this process. Two different models of Bcl-XL function have been proposed. In one, Bcl-XL binds to an activator, thereby preventing Bax activation.

Development of dimeric modulators for anti-apoptotic Bcl-2 proteins.

Bcl-2 family proteins can be classified into two subfamilies--anti-apoptotic members and pro-apoptotic members. Mechanistically, these two subfamilies can antagonize each other through heterodimerization while homodimerization has been proposed for each subfamily to carry out their corresponding anti-apoptotic or pro-apoptotic functions. To date, many small-molecule antagonists against anti-apoptotic Bcl-2 proteins have been developed, which are monomeric modulators.