Programmable Selfâ Locking Origami Mechanical Metamaterials

Developing mechanical metamaterials with programmable properties is an emerging topic receiving wide attention. While the programmability mainly originates from structural multistability in previously designed metamaterials, here it is shown that nonflatâ foldable origami provides a new platform to achieve programmability via its intrinsic selfâ locking and reconfiguration capabilities. Working with the singleâ collinear degreeâ 4 vertex origami tessellation, it is found that each unit cell can selfâ lock at a nonflat configuration and, therefore, possesses wide design space to program its foldability and relative density. Experiments and numerical analyses are combined to demonstrate that by switching the deformation modes of the constituent cell from prelocking folding to postlocking pressing, its stiffness experiences a sudden jump, implying a limitingâ stopper effect. Such a stiffness jump is generalized to a multisegment piecewise stiffness profile in a multilayer model. Furthermore, it is revealed that via strategically switching the constituent cells’ deformation modes through passive or active means, the nâ layer metamaterial’s stiffness is controllable among 2n target stiffness values. Additionally, the piecewise stiffness can also trigger bistable responses dynamically under harmonic excitations, highlighting the metamaterial’s rich dynamic performance. These unique characteristics of selfâ locking origami present new paths for creating programmable mechanical metamaterials with in situ controllable mechanical properties.An origami mechanical metamaterial with programmable lockingâ induced piecewise stiffness is demonstrated. The kinematical and mechanical properties of the metamaterial can be strategically tuned by switching the deformation mode of the constituent cells between prelocking folding and postlocking pressing. The capabilities uncovered present new pathways for achieving programmability in metamaterials and metastructures.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143652/1/adma201706311_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143652/2/adma201706311-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143652/3/adma201706311.pd

Human immunodeficiency virus type 1 mutants resistant to nonnucleoside inhibitors of reverse transcriptase arise in tissue culture

We have recently described a nonnucleoside compound that specifically inhibits the reverse transcriptase of human immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS. This compound, nevirapine (BI-RG-587), interacts with highly conserved tyrosine residues at positions 181 and 188 in the reverse transcriptase to inhibit the recombinant enzyme and virus replication in cell culture with 50% inhibitory concentrations in the 40 nM range. HIV-1 variants resistant to nevirapine emerged with passage in cell culture in the presence of drug. This resistant phenotype was stable with continued passage in the absence of drug. These mutants had a substitution of cysteine for the tyrosine at position 181. Introduction of this mutation into the recombinant enzyme increased the inhibitory concentration of nevirapine 100-fold. Substitution of cysteine for tyrosine at residue 181 into the wild-type viral genome conferred a similar reduction in susceptibility to nevirapine. Mutants were also resistant to a tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one and -thione derivative and two 6-phenylthiouracil derivatives but retained their sensitivity to the other reverse transcriptase inhibitors, 3'-azido-3'-deoxythymidine and foscarnet

Development of a Surface Plasmon Resonance Biosensor for Real-Time Detection of Osteogenic Differentiation in Live Mesenchymal Stem Cells

Surface plasmon resonance (SPR) biosensors have been recognized as a useful tool and widely used for real-time dynamic analysis of molecular binding affinity because of its high sensitivity to the change of the refractive index of tested objects. The conventional methods in molecular biology to evaluate cell differentiation require cell lysis or fixation, which make investigation in live cells difficult. In addition, a certain amount of cells are needed in order to obtain adequate protein or messenger ribonucleic acid for various assays. To overcome this limitation, we developed a unique SPR-based biosensing apparatus for real-time detection of cell differentiation in live cells according to the differences of optical properties of the cell surface caused by specific antigen-antibody binding. In this study, we reported the application of this SPR-based system to evaluate the osteogenic differentiation of mesenchymal stem cells (MSCs). OB-cadherin expression, which is up-regulated during osteogenic differentiation, was targeted under our SPR system by conjugating antibodies against OB-cadherin on the surface of the object. A linear relationship between the duration of osteogenic induction and the difference in refractive angle shift with very high correlation coefficient was observed. To sum up, the SPR system and the protocol reported in this study can rapidly and accurately define osteogenic maturation of MSCs in a live cell and label-free manner with no need of cell breakage. This SPR biosensor will facilitate future advances in a vast array of fields in biomedical research and medical diagnosis

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049