MULTI-K: accurate classification of microarray subtypes using ensemble k-means clustering

<p>Abstract</p> <p>Background</p> <p>Uncovering subtypes of disease from microarray samples has important clinical implications such as survival time and sensitivity of individual patients to specific therapies. Unsupervised clustering methods have been used to classify this type of data. However, most existing methods focus on clusters with compact shapes and do not reflect the geometric complexity of the high dimensional microarray clusters, which limits their performance.</p> <p>Results</p> <p>We present a cluster-number-based ensemble clustering algorithm, called <it>MULTI-K</it>, for microarray sample classification, which demonstrates remarkable accuracy. The method amalgamates multiple <it>k</it>-means runs by varying the number of clusters and identifies clusters that manifest the most robust co-memberships of elements. In addition to the original algorithm, we newly devised the <it>entropy-plot </it>to control the separation of singletons or small clusters. MULTI-K, unlike the simple <it>k</it>-means or other widely used methods, was able to capture clusters with complex and high-dimensional structures accurately. MULTI-K outperformed other methods including a recently developed ensemble clustering algorithm in tests with five simulated and eight real gene-expression data sets.</p> <p>Conclusion</p> <p>The geometric complexity of clusters should be taken into account for accurate classification of microarray data, and ensemble clustering applied to the number of clusters tackles the problem very well. The C++ code and the data sets tested are available from the authors.</p

High-Performance PVC Gel for Adaptive Micro-Lenses with Variable Focal Length.

This paper presents a bio-inspired adaptive micro-lens with electrically tunable focus made of non-ionic high-molecular-weight polyvinyl chloride (PVC) gel. The optical device mimics the design of the crystalline lens and ciliary muscle of the human eye. It consists of a plano-convex PVC gel micro-lens on Indium Tin Oxide (ITO) glass, confined with an annular electrode operating as an artificial ciliary muscle. Upon electrical activation, the electroactive adhesive force of the PVC gel is exerted on the annular anode electrode, which reduces the sagittal height of the plano-convex PVC gel lens, resulting in focal length variation of the micro-lens. The focal length increases from 3.8 mm to 22.3 mm as the applied field is varied from 200 V/mm to 800 V/mm, comparable to that of the human lens. The device combines excellent optical characteristics with structural simplicity, fast response speed, silent operation, and low power consumption. The results show the PVC gel micro-lens is expected to open up new perspectives on practical tunable optics

Unleashing the full potential of Hsp90 inhibitors as cancer therapeutics through simultaneous inactivation of Hsp90, Grp94, and TRAP1

Cancer therapeutics: Extending a drug&apos;s reach A new drug that blocks heat shock proteins (HSPs), helper proteins that are co-opted by cancer cells to promote tumor growth, shows promise for cancer treatment. Several drugs have targeted HSPs, since cancer cells are known to hijack these helper proteins to shield themselves from destruction by the body. However, the drugs have had limited success. Hye-Kyung Park and Byoung Heon Kang at Ulsan National Institutes of Science and Technology in South Korea and coworkers noticed that the drugs were not absorbed into mitochondria, a key cellular compartment, and HSPs in this compartment were therefore not being blocked. They identified a new HSP inhibitor that can reach every cellular compartment and inhibit all HSPs. Testing in mice showed that this inhibitor effectively triggered death of tumor cells, and therefore shows promise for anti-cancer therapy. The Hsp90 family proteins Hsp90, Grp94, and TRAP1 are present in the cell cytoplasm, endoplasmic reticulum, and mitochondria, respectively; all play important roles in tumorigenesis by regulating protein homeostasis in response to stress. Thus, simultaneous inhibition of all Hsp90 paralogs is a reasonable strategy for cancer therapy. However, since the existing pan-Hsp90 inhibitor does not accumulate in mitochondria, the potential anticancer activity of pan-Hsp90 inhibition has not yet been fully examined in vivo. Analysis of The Cancer Genome Atlas database revealed that all Hsp90 paralogs were upregulated in prostate cancer. Inactivation of all Hsp90 paralogs induced mitochondrial dysfunction, increased cytosolic calcium, and activated calcineurin. Active calcineurin blocked prosurvival heat shock responses upon Hsp90 inhibition by preventing nuclear translocation of HSF1. The purine scaffold derivative DN401 inhibited all Hsp90 paralogs simultaneously and showed stronger anticancer activity than other Hsp90 inhibitors. Pan-Hsp90 inhibition increased cytotoxicity and suppressed mechanisms that protect cancer cells, suggesting that it is a feasible strategy for the development of potent anticancer drugs. The mitochondria-permeable drug DN401 is a newly identified in vivo pan-Hsp90 inhibitor with potent anticancer activity