Tissue and Metabolic Engineering of Biohybrid Artificial Organs

In an effort to develop a biohybrid artificial organ, mammalian cells were engineered with several properties to make them adept in secreting therapeutic proteins and surviving low oxygen levels in an encapsulated environment. Three cell lines, C2C12, Jurkat, and HEK293, were investigated for their ability to secrete human interleukin 2 (hIL2), which can serve as an anti-cancer agent. An intracellular fluorescent protein marker was independently expressed using an internal ribosome entry site sequence so that hIL2 remained active and free for secretion. DsRed fluorescent protein markers were used since red light is known to be transmissible through mammalian tissue. Transient transfection of all three cell lines proved that internal red fluorescence measurements were indeed linearly correlated with the concentration of hIL2 secreted. To increase the survivability of encapsulated cultures, cells were engineered with an anti-apoptotic gene, bcl-2Delta, placed under the control of a hypoxia sensitive promoter. This protective system was found to lessen both hypoxia induced necrosis and apoptosis. To complete the biohybrid system, a novel hydrogel (mTG-Gel), utilizing microbial transglutaminase (mTG) to enyzmatically crosslink gelatin, was developed as a biocompatible cellular scaffold for encapsulating the engineered cells. These gels were stable at physiological temperature (37 oC) and could be tailored for enzymatic stability. Specifically, HEK293 cells that were metabolically engineered with all the previous characteristics were encapsulated in 4% mTG-Gels. In situ analysis of DsRed fluorescence showed that cells overlayed with mTG-Gel exhibited reductions in fluorescence with increasing height of gel. Human IL2 diffusion through the hydrogel into overlaying media was found to exhibit the expected dependence on the square of the gel thickness. Diffusion cells were used to determine an effective diffusion coefficient for hIL2, which compared well to that obtained from the gel-overlay cell culture experiments

Identifiability of the Simplex Volume Minimization Criterion for Blind Hyperspectral Unmixing: The No Pure-Pixel Case

In blind hyperspectral unmixing (HU), the pure-pixel assumption is well-known to be powerful in enabling simple and effective blind HU solutions. However, the pure-pixel assumption is not always satisfied in an exact sense, especially for scenarios where pixels are heavily mixed. In the no pure-pixel case, a good blind HU approach to consider is the minimum volume enclosing simplex (MVES). Empirical experience has suggested that MVES algorithms can perform well without pure pixels, although it was not totally clear why this is true from a theoretical viewpoint. This paper aims to address the latter issue. We develop an analysis framework wherein the perfect endmember identifiability of MVES is studied under the noiseless case. We prove that MVES is indeed robust against lack of pure pixels, as long as the pixels do not get too heavily mixed and too asymmetrically spread. The theoretical results are verified by numerical simulations

Semiblind ML OSTBC-OFDM detection in block fading channels

[[abstract]]This paper presents a semiblind maximum-likelihood (ML) detector for the orthogonal space-time block coded orthogonal frequency division multiplexing (OSTBC-OFDM) system. Many existing blind/ semiblind OSTBC-OFDM receivers typically require that the channel is static over a multitude of OSTBC-OFDM blocks. The proposed method is specifically for detection over one OSTBC-OFDM block only, and hence is well suited to block fading channels. The presented identifiability analysis shows that the data can be uniquely identified in a probability one sense by using one pilot code only, in contrast to the pilot-based least-squares channel estimator which requires at least L pilot codes where L is the channel length. Simulation examples are then presented to show the efficacy of the proposed detector.[[fileno]]2030157030006[[department]]電機工程學

A convex analysis based criterion for blind separation of non-negative sources

[[abstract]]In this paper, we apply convex analysis to the problem of blind source separation (BSS) of non-negative signals. Under realistic assumptions applicable to many real-world problems such as multichannel biomedical imaging, we formulate a new BSS criterion that does not require statistical source independence, a fundamental assumption to many existing BSS approaches. The new criterion guarantees perfect separation (in the absence of noise), by constructing a convex set from the observations and then finding the extreme points of the convex set. Some experimental results are provided to demonstrate the efficacy of the proposed method. © 2007 IEEE.[[fileno]]2030157030001[[department]]電機工程學

The association of RANTES polymorphism with severe acute respiratory syndrome in Hong Kong and Beijing Chinese

<p>Abstract</p> <p>Background</p> <p>Chemokines play important roles in inflammation and antiviral action. We examined whether polymorphisms of <it>RANTES, IP-10 </it>and <it>Mig </it>affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS).</p> <p>Methods</p> <p>We tested the polymorphisms of <it>RANTES, IP-10 </it>and <it>Mig </it>for their associations with SARS in 495 Hong Kong Chinese SARS patients and 578 controls. Then we tried to confirm the results in 356 Beijing Chinese SARS patients and 367 controls.</p> <p>Results</p> <p><it>RANTES </it>-28 G allele was associated with SARS susceptibility in Hong Kong Chinese (<it>P </it>< 0.0001, OR = 2.80, 95%CI:2.11–3.71). Individuals with <it>RANTES </it>-28 CG and GG genotypes had a 3.28-fold (95%CI:2.32–4.64) and 3.06-fold (95%CI:1.47–6.39) increased risk of developing SARS respectively (<it>P </it>< 0.0001). This -28 G allele conferred risk of death in a gene-dosage dependent manner (<it>P </it>= 0.014) with CG and GG individuals having a 2.12-fold (95% CI: 1.11–4.06) and 4.01-fold (95% CI: 1.30–12.4) increased risk. For the replication of <it>RANTES </it>data in Beijing Chinese, the -28 G allele was not associated with susceptibility to SARS. However, -28 CG (OR = 4.27, 95%CI:1.64–11.1) and GG (OR = 3.34, 95%CI:0.37–30.7) were associated with admission to intensive care units or death due to SARS (<it>P </it>= 0.011).</p> <p>Conclusion</p> <p><it>RANTES </it>-28 G allele plays a role in the pathogenesis of SARS.</p