71 research outputs found

    Some results on 2nβˆ’m2^{n-m} designs of resolution IV with (weak) minimum aberration

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    It is known that all resolution IV regular 2nβˆ’m2^{n-m} designs of run size N=2nβˆ’mN=2^{n-m} where 5N/16<n<N/25N/16<n<N/2 must be projections of the maximal even design with N/2N/2 factors and, therefore, are even designs. This paper derives a general and explicit relationship between the wordlength pattern of any even 2nβˆ’m2^{n-m} design and that of its complement in the maximal even design. Using these identities, we identify some (weak) minimum aberration 2nβˆ’m2^{n-m} designs of resolution IV and the structures of their complementary designs. Based on these results, several families of minimum aberration 2nβˆ’m2^{n-m} designs of resolution IV are constructed.Comment: Published in at http://dx.doi.org/10.1214/08-AOS670 the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

    Novel Membrane-Associated Androgen Receptor Splice Variant Potentiates Proliferative and Survival Responses in prostate cancer cells

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    Progression from the androgen-sensitive to androgen-insensitive (or castration-resistant) stage is the major obstacle for sustained effectiveness of hormonal therapy for prostate cancer. The androgen receptor (AR) and its splice variants play important roles in regulating the transcription program essential for castration resistance. Here, we report the identification of a novel AR splice variant, designated as AR8, which is up-regulated in castration-resistant prostate cancer cells. AR8 is structurally different from other known AR splice variants because it lacks a DNA binding domain and therefore, unlikely functions as a transcription factor on its own. Immunofluorescence staining revealed that AR8 was primarily localized on the plasma membrane, possibly through palmitoylation of two cysteine residues within its unique C-terminal sequence. Mutation of these putative palmitoylation sites in AR8 led to loss of its plasma membrane localization. In addition, we demonstrated that overexpression of AR8 in prostate cancer cells promoted association of Src and AR with the EGF receptor in response to EGF treatment and enhanced tyrosine phosphorylation of AR. Conversely, specific knockdown of AR8 expression in prostate cancer cells compromised EGF-induced Src activation and AR phosphorylation. This effect was accompanied with attenuation of proliferation and increased apoptosis in prostate cancer cells cultured in androgen-depleted medium. We also showed that AR8 was required for optimal transcriptional activity of AR in response to treatment of both androgen and EGF. Taken together, our results demonstrate that the membrane-associated AR8 isoform may contribute to castration resistance by potentiating AR-mediated proliferative and survival responses to hormones and growth factors

    Tyrosine Kinase ETK/BMX Is Up-Regulated in Bladder Cancer and Predicts Poor Prognosis in Patients with Cystectomy

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    Deregulation of the non-receptor tyrosine kinase ETK/BMX has been reported in several solid tumors. In this report, we demonstrated that ETK expression is progressively increased during bladder cancer progression. We found that down-regulation of ETK in bladder cancer cells attenuated STAT3 and AKT activity whereas exogenous overexpression of ETK had opposite effects, suggesting that deregulation of ETK may attribute to the elevated activity of STAT3 and AKT frequently detected in bladder cancer. The survival, migration and invasion of bladder cancer cells were significantly compromised when ETK expression was knocked down by a specific shRNA. In addition, we showed that ETK localizes to mitochondria in bladder cancer cells through interacting with Bcl-XL and regulating ROS production and drug sensitivity. Therefore, ETK may play an important role in regulating survival, migration and invasion by modulating multiple signaling pathways in bladder cancer cells. Immunohistochemistry analysis on tissue microarrays containing 619 human bladder tissue samples shows that ETK is significantly upregulated during bladder cancer development and progression and ETK expression level predicts the survival rate of patients with cystectomy. Taken together, our results suggest that ETK may potentially serve as a new drug target for bladder cancer treatment as well as a biomarker which could be used to identify patients with higher mortality risk, who may be benefited from therapeutics targeting ETK activity

    Some projective properties of fractional factorial designs

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    Fractional factorial designs have a long history of successful use in factor screening experiments. When only a few factors are expected to be relevant, knowledge of their low-dimension projections is valuable. The projection properties of the 2Rn-m fractional factorial design into any k dimensions (k[less-than-or-equals, slant]R) are well known. However, there is no further discussion on the projections of such design into any dimensions which are larger than R. In this paper, we provide a complete characterization of such projections into (R + 1) to (R + [(R - 1)/2]) dimensions.Fractional factorial design Minimum aberration Resolution Wordlength pattern

    Doubling and projection: A method of constructing two-level designs of resolution IV

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    Knowledge and preference for breast conservation therapy among women without breast cancer

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    We interviewed 419 adult women in Minnesota, who were selected at random and without a history of breast cancer, to ascertain what percentage could correctly report that cure was the same for breast conservation therapy and mastectomy, what percentage would state a preference for breast conservation therapy rather than mastectomy, and characteristics associated with these outcomes. Nearly all women (n = 360; 86%) had heard of both mastectomy and breast conservation therapy; among these women, 37% correctly reported that the two treatments were equally efficacious. Given a scenario where they were diagnosed with breast cancer amenable to either treatment, 58% of participants stated a preference for breast conservation therapy. Older women were less likely than younger women to know that cure was the same for breast conservation therapy and mastectomy (adjusted OR = 0.5, 95% CI 0.2, 1.0), and women residing in urban areas were more likely to prefer breast conservation therapy over mastectomy compared to rural residents (adjusted OR = 2.2, 95% CI 1.3, 3.8). Comparing these findings to women diagnosed with breast cancer in Minnesota, breast conservation therapy was found to be performed less frequently than preference for such therapy among women in our study would suggest. Educating women prior to diagnosis about breast cancer treatment options, and exploring reasons for the gap between actual utilization of breast conservation therapy and prediagnosis preference, may be indicated. Copyright (C) 2000 Elsevier Science Inc
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