Cancer is a leading cause of human mortality worldwide, and is expected to soon become the overall leading cause of death in the United States. Some cancers are hormone-related, including the sex-specific cancers of the breast (predominantly in women) and prostate (in men). In both cases, early stage tumors are responsive to inhibitory endocrine-based therapies. However, both cancers progress to hormone-nonresponsive states and this is in part due to altered properties of the primary nuclear hormone receptor signaling pathway (estrogen receptor [ER] in breast; androgen receptor [AR] in prostate). Other nuclear receptors are thus being investigated as therapeutic targets due to their crosstalk with hormone receptor pathways and these include the aryl hydrocarbon receptor (AhR), peroxisome proliferator activated receptor γ(PPARγ, retinoic acid receptor and retinoid X receptor (RAR/RXR), and vitamin D receptor (VDR). Previous studies have demonstrated that the AhR mediates chemoprotective, antiestrogenic, and tumoristatic effects in experimental models, and relatively non-toxic selective aryl hydrocarbon receptor modulators (SAhRMs) have been developed. Studies in this dissertation have investigated the therapeutic properties of a new class of compounds related to the SAhRM 3,3‘-diindolylmethane (DIM) in models of breast cancer. Additionally, the potential therapeutic role of the AhR in human prostate cancer cells has been investigated. Several ring- and methylene-substituted DIMs exhibited antiestrogenic and tumoristatic activities in breast cancer cells and in carcinogen-induced rat mammary tumors. At least some of the methylene-substituted DIMs act through PPARγ. The AhR is expressed in LNCaP and iv 22Rv1 prostate cancer cells and AhR agonists inhibit cell growth and AR-induced transactivation through pathways independent of androgen receptor downregulation.

The Nyquist WDM system realizes a terabit high spectral efficiency transmission system by allocating several subcarriers close to or equal to the baud rate. This system achieves optimal performance by maintaining both temporal and spectral orthogonality. However, ISI and ICI effects are inevitable in practical Nyquist WDM implementations due to the imperfect channel response and tight channel spacing and may cause significant performance degradations. Our primary research goals are to combat the ISI effects via the transmitter digital pre-shaping and to remove the ICI impairments at the receiver using MIMO signal processing. First we propose two novel blind channel estimation techniques that enable the transmitter pre-shaping design for the ISI effects mitigation. Both numerical and experimental results demonstrate that the two methods are very effective in compensating the narrow band filtering and are very robust to channel estimation noise. Besides pre-shaping, the DAC-enabled transmitter chromatic dispersion compensation is also demonstrated in a system with high LO laser linewidth. Next a novel “super-receiver” structure is proposed, where different subchannels are synchronously sampled, and the baseband signals from three adjacent subchannels are processed jointly to remove ICI penalty. Three different ICI compensation methods are introduced and their performances compared. The important pre-processes that enable a successful ICI compensation are also elaborated. Despite ICI compensation, the joint carrier phase recovery based on the Viterbi-Viterbi algorithm is also studied in the carrier phase locked systems. In-band crosstalk arises from the imperfect switch elements in the add-drop process of ROADM-enabled DWDM systems and may cause significant performance degradation. Our third research topic is to demonstrate a systematic way to analyze and predict the in-band crosstalk-induced penalty. In this work, we propose a novel crosstalk-to-ASE noise weighting factor that can be combined with the weighted crosstalk weighting metric to incorporate the in-band crosstalk noise into the Gaussian noise model for performance prediction and analysis. With the aid of the Gaussian noise model, the in-band crosstalk-induced nonlinear noise is also studied. Both simulations and experiments are used to validate the proposed methods.

ITC/USA 2013 Conference Proceedings / The Forty-Ninth Annual International Telemetering Conference and Technical Exhibition / October 21-24, 2013 / Bally's Hotel & Convention Center, Las Vegas, NV / This paper described the details of subjective validation for visually lossless compression of stereoscopic 3 dimensional (3D) images. The subjective testing method employed in this work is adapted from methods used previously for visually lossless compression of 2 dimensional (2D) images. Confidence intervals on the correct response rate obtained from the subjective validation of compressed stereo pairs provide reliable evidence to indicate that the compressed stereo pairs are visually lossless.

ITC/USA 2012 Conference Proceedings / The Forty-Eighth Annual International Telemetering Conference and Technical Exhibition / October 22-25, 2012 / Town and Country Resort & Convention Center, San Diego, California / This paper proposes a method of measuring visibility thresholds for quantization distortion in JPEG2000 for compression of stereoscopic 3D images. The crosstalk effect is carefully considered to ensure that quantization errors in each channel of stereoscopic images are imperceptible to both eyes. A model for visibility thresholds is developed to reduce the daunting number of measurements required for subjective experiments.

No description available.

Currently two main tracks are considered for integration of photonic circuits. Silicon based integration may be more cost effective; however implementation of some functionalities like laser, is problematic. In contrast InP offers complete solution of photonic integration including laser diodes. Additionally, much higher speeds may be anticipated from InP based integration. As in the case of ordinary integrated circuits, attempts to increase degree (density) lead to undesired coupling-crosstalk between the components. Three types of cross coupling may be clearly distinguished: optical, RF(electric) and thermal. Each of them has its specifics, physical mechanisms and methods of analysis. Modeling RF crosstalk will be in the focus of this project. To drive active components, such as laser and photodiodes, conducting tracks are integrated with photonic components. In multichannel photonic IC chips these tracks become very dense leading to strong parasitic electrical couplings between them. This crosstalk becomes more problematic in high speed photonic IC chips where the frequency of the RF signals (modulation, detection) is in the range up to 10GHz and beyond. Thus modeling of the crosstalk between RF tracks (also between RF and DC) is of prime importance. This is the main task of the project. A further task is analysis of the crosstalk using developed models and considering designs allowing reduced cross coupling.

Histone phosphorylation is often a direct outcome of activated intracellular signaling pathways, and functions to translate extracellular signals into appropriate biological outputs such as changes in gene expression. Growth factors and cellular stress trigger rapid and transient expression of immediate-early genes (such as c-fos, c-jun) in mammalian cells, and their induction strongly correlates with a transient phosphorylation of S10 and S28 on histone H3. While many signaling cascades that lead to H3 phosphorylation have been mapped out, mechanistic details of the downstream events and how H3 phosphorylation contributes to transcriptional activation are still poorly defined. To investigate the direct effects of H3 phosphorylation on transcription, we targeted the H3 kinase MSK1 to endogenous c-fos promoter, and found that this is sufficient to activate its expression. Moreover, targeting MSK1 to the tissue-specific -globin gene induces H3S28 phosphorylation and reactivates expression of this polycomb-silenced gene. Mechanistically, H3S28 phosphorylation not only disrupts binding of polycomb repressive complexes, but also induces a methyl-acetylation switch of the adjacent K27 residue. This provides the first indication that H3 phosphorylation is involved in antagonizing polycomb silencing. To further identify post-translational modifications (PTMs) that function together with MSK1-mediated H3 phosphorylation, I developed a novel nucleosome purification approach called Biotinylation-assisted Isolation of CO-modified Nucleosomes (BICON). This technique combines in vivo biotinylation by BirA and H3 phosphorylation by MSK1, allowing enrichment of phosphorylated nucleosomes using streptavidin. I found that MSK1-phosphorylated nucleosomes are hyper-acetylated on H3 and H4, and importantly, I identified a trans-tail crosstalk between H3 phosphorylation and H4 acetylation on K12. This proof-of-principle study demonstrates that BICON can be further adapted to study PTMs and crosstalks associated with other histone-modifying enzymes. Taken together, work described in this thesis shows that histone H3 phosphorylation can initiate additional PTM changes on other residues within the nucleosome, and such crosstalk plays an important role in regulating gene expression.

Histone phosphorylation is often a direct outcome of activated intracellular signaling pathways, and functions to translate extracellular signals into appropriate biological outputs such as changes in gene expression. Growth factors and cellular stress trigger rapid and transient expression of immediate-early genes (such as c-fos, c-jun) in mammalian cells, and their induction strongly correlates with a transient phosphorylation of S10 and S28 on histone H3. While many signaling cascades that lead to H3 phosphorylation have been mapped out, mechanistic details of the downstream events and how H3 phosphorylation contributes to transcriptional activation are still poorly defined. To investigate the direct effects of H3 phosphorylation on transcription, we targeted the H3 kinase MSK1 to endogenous c-fos promoter, and found that this is sufficient to activate its expression. Moreover, targeting MSK1 to the tissue-specific -globin gene induces H3S28 phosphorylation and reactivates expression of this polycomb-silenced gene. Mechanistically, H3S28 phosphorylation not only disrupts binding of polycomb repressive complexes, but also induces a methyl-acetylation switch of the adjacent K27 residue. This provides the first indication that H3 phosphorylation is involved in antagonizing polycomb silencing. To further identify post-translational modifications (PTMs) that function together with MSK1-mediated H3 phosphorylation, I developed a novel nucleosome purification approach called Biotinylation-assisted Isolation of CO-modified Nucleosomes (BICON). This technique combines in vivo biotinylation by BirA and H3 phosphorylation by MSK1, allowing enrichment of phosphorylated nucleosomes using streptavidin. I found that MSK1-phosphorylated nucleosomes are hyper-acetylated on H3 and H4, and importantly, I identified a trans-tail crosstalk between H3 phosphorylation and H4 acetylation on K12. This proof-of-principle study demonstrates that BICON can be further adapted to study PTMs and crosstalks associated with other histone-modifying enzymes. Taken together, work described in this thesis shows that histone H3 phosphorylation can initiate additional PTM changes on other residues within the nucleosome, and such crosstalk plays an important role in regulating gene expression.

Thesis (M.S.)--Rutgers University, 2007. / "Graduate Program in Electrical and Computer Engineering." Includes bibliographical references (p. 44-49).

Thesis (M. Eng.)--Carleton University, 1992. / Also available in electronic format on the Internet.