Power law relationship between diffusion coefficients in multi-component glass forming liquids

The slow down of dynamics in glass forming liquids as the glass transition is approached has been characterised through the Adam-Gibbs relation, which relates relaxation time scales to the configurational entropy. The Adam-Gibbs relation cannot apply simultaneously to all relaxation times scales unless they are coupled, and exhibit closely related temperature dependences. The breakdown of the Stokes-Einstein relation presents an interesting situation to the contrary, and in analysing it, it has recently been shown that the Adam-Gibbs relation applies to diffusion coefficients rather than to viscosity or structural relaxation times related to the decay of density fluctuations. However, for multi-component liquids -- the typical cases considered in computer simulations, metallic glass formers, etc. -- such a statement raises the question of which diffusion coefficient is described by the Adam-Gibbs relation. All diffusion coefficients can be consistently described by the Adam-Gibbs relation if they bear a power law relationship with each other. Remarkably, we find that for a wide range of glass formers, and for a wide range of temperatures spanning the normal and the slow relaxation regimes, such a relationship holds. We briefly discuss possible rationalisations of the observed behaviour

Power law relationship between diffusion coefficients in multi-component glass forming liquids

The slow down of dynamics in glass forming liquids as the glass transition is approached has been characterised through the Adam-Gibbs relation, which relates relaxation time scales to the configurational entropy. The Adam-Gibbs relation cannot apply simultaneously to all relaxation times scales unless they are coupled, and exhibit closely related temperature dependences. The breakdown of the Stokes-Einstein relation presents an interesting situation to the contrary, and in analysing it, it has recently been shown that the Adam-Gibbs relation applies to diffusion coefficients rather than to viscosity or structural relaxation times related to the decay of density fluctuations. However, for multi-component liquids --the typical cases considered in computer simulations, metallic glass formers, etc.-- such a statement raises the question of which diffusion coefficient is described by the Adam-Gibbs relation. All diffusion coefficients can be consistently described by the Adam-Gibbs relation if they bear a power law relationship with each other. Remarkably, we find that for a wide range of glass formers, and for a wide range of temperatures spanning the normal and the slow relaxation regimes, such a relationship holds. We briefly discuss possible rationalisations of the observed behaviour

Overexpression of Cdc20 Leads to Impairment of the Spindle Assembly Checkpoint and Aneuploidization in Oral Cancer

Defects in the spindle assembly checkpoint are thought to be responsible for an increased rate of aneuploidization during tumorigenesis. Despite a plethora of information on the correlation between BUB-MAD gene expression levels and defects in the spindle checkpoint, very little is known about alteration of another important spindle checkpoint protein, Cdc20, in human cancer and its role in tumor aneuploidy. We observed overexpression of CDC20 in several oral squamous cell carcinoma (OSCC) cell lines and primary head and neck tumors and provide evidence that such overexpression of CDC20 is associated with premature anaphase promotion, resulting in mitotic abnormalities in OSCC cell lines. We also reconstituted the chromosomal instability phenotype in a chromosomally stable OSCC cell line by overexpressing CDC20. Thus, abnormalities in the cellular level of Cdc20 may deregulate the timing of anaphase promoting complex (APC/C) in promoting premature anaphase, which often results in aneuploidy in the tumor cells

Reporter nanoparticle that monitors its anticancer efficacy in real time

The ability to monitor the efficacy of an anticancer treatment in real time can have a critical effect on the outcome. Currently, clinical readouts of efficacy rely on indirect or anatomic measurements, which occur over prolonged time scales postchemotherapy or postimmunotherapy and may not be concordant with the actual effect. Here we describe the biology-inspired engineering of a simple 2-in-1 reporter nanoparticle that not only delivers a cytotoxic or an immunotherapy payload to the tumor but also reports back on the efficacy in real time. The reporter nanoparticles are engineered from a novel two-staged stimuli-responsive polymeric material with an optimal ratio of an enzyme-cleavable drug or immunotherapy (effector elements) and a drug function-activatable reporter element. The spatiotemporally constrained delivery of the effector and the reporter elements in a single nanoparticle produces maximum signal enhancement due to the availability of the reporter element in the same cell as the drug, thereby effectively capturing the temporal apoptosis process. Using chemotherapy-sensitive and chemotherapy-resistant tumors in vivo, we show that the reporter nanoparticles can provide a real-time noninvasive readout of tumor response to chemotherapy. The reporter nanoparticle can also monitor the efficacy of immune checkpoint inhibition in melanoma. The self-reporting capability, for the first time to our knowledge, captures an anticancer nanoparticle in action in vivo.Breast Cancer Research Program (U.S.) (Collaborative Innovator Grant W81XWH- 09-1-0700)National Institutes of Health (U.S.) (Grant 1R01CA135242)United States. Department of Defense (Breakthrough Award BC132168)American Lung Association (Innovation Award LCD-259932-N)American Cancer Society (Postdoctoral Fellowship 122854-PF-12-226-01-CDD