439 research outputs found
KSU Chorale, Chamber Singers and KSU Symphony Orchestra
The KSU School of Music presents a special performance featuring the KSU Symphony Orchestra, led by Director of Orchestral Studies Dr. Nathaniel Parker, and KSU Chamber Singers and University Chorale led by Dr. Leslie Blackwell, Director of Choral Activities. The program concludes with a performance of Mozart\u27s Requiem (K. 626) and will also include additional works performed during the first half: Ola Gjeilo\u27s The Rose performed by KSU Chamber Singers and Chorale and Michael Daugherty\u27s Red Cape Tango performed by KSU Symphony Orchestra.https://digitalcommons.kennesaw.edu/musicprograms/2181/thumbnail.jp
Development and exploitation of a novel mutant androgen receptor modelling strategy to identify new targets for advanced prostate cancer therapy
The persistence of androgen receptor (AR) signalling in castrate-resistant prostate cancer (CRPC) highlights the unmet clinical need for the development of more effective AR targeting therapies. A key mechanism of therapy-resistance is by selection of AR mutations that convert anti-androgens to agonists enabling the retention of androgenic signalling in CRPC. To improve our understanding of these receptors in advanced disease we developed a physiologically-relevant model to analyse the global functionality of AR mutants in CRPC. Using the bicalutamide-activated ARW741L/C mutation as proof of concept, we demonstrate that this mutant confers an androgenic-like signalling programme and growth promoting phenotype in the presence of bicalutamide. Transcriptomic profiling of ARW741L highlighted key genes markedly up-regulated by the mutant receptor, including TIPARP, RASD1 and SGK1. Importantly, SGK1 expression was found to be highly expressed in the KUCaP xenograft model and a CRPC patient biopsy sample both of which express the bicalutamide-activated receptor mutant. Using an SGK1 inhibitor, ARW741L transcriptional and growth promoting activity was reduced indicating that exploiting functional distinctions between receptor isoforms in our model may provide new and effective therapies for CRPC patients
Collage 2019
An exciting highlight each season, Collage is the signature production of the School of Music and a major fundraising event for supporting scholarships for music students. This special performance features over 200 student and faculty performers and includes jazz, orchestra, choir, band, percussion, and opera selections for soloists, chamber groups, and ensembles. Special lighting effects and stage design combine with the diverse and exciting program presented as rapid-fire, flowing vignettes to create a truly unique performance.https://digitalcommons.kennesaw.edu/musicprograms/2161/thumbnail.jp
The realisation of targeted antitumour therapy
Better understanding of the pathways regulating proliferation and metastasis of cancer cells has led to the development of novel molecular-targeted therapies. The number of molecular-targeted agents approved for use in the clinic is growing, with many more in clinical trials. Most of these compounds can be broadly classified into two main categories: monoclonal antibodies and small-molecule tyrosine kinase inhibitors. The pathological processes targeted include vascular endothelial growth factor-dependent tumour angiogenesis and epidermal growth factor receptor-dependent tumour cell proliferation and survival. Unlike conventional chemotherapy, molecular-targeted agents offer the potential advantages of a relatively high therapeutic window and use in combination with other anticancer strategies without overlapping toxicity. It is hoped that these drugs will become valuable therapeutic tools within the multimodal approach to treating cancer. Recent progress in targeted antitumour therapy is discussed, with a focus on antiangiogenesis
Sampling-based Algorithms for Optimal Motion Planning
During the last decade, sampling-based path planning algorithms, such as
Probabilistic RoadMaps (PRM) and Rapidly-exploring Random Trees (RRT), have
been shown to work well in practice and possess theoretical guarantees such as
probabilistic completeness. However, little effort has been devoted to the
formal analysis of the quality of the solution returned by such algorithms,
e.g., as a function of the number of samples. The purpose of this paper is to
fill this gap, by rigorously analyzing the asymptotic behavior of the cost of
the solution returned by stochastic sampling-based algorithms as the number of
samples increases. A number of negative results are provided, characterizing
existing algorithms, e.g., showing that, under mild technical conditions, the
cost of the solution returned by broadly used sampling-based algorithms
converges almost surely to a non-optimal value. The main contribution of the
paper is the introduction of new algorithms, namely, PRM* and RRT*, which are
provably asymptotically optimal, i.e., such that the cost of the returned
solution converges almost surely to the optimum. Moreover, it is shown that the
computational complexity of the new algorithms is within a constant factor of
that of their probabilistically complete (but not asymptotically optimal)
counterparts. The analysis in this paper hinges on novel connections between
stochastic sampling-based path planning algorithms and the theory of random
geometric graphs.Comment: 76 pages, 26 figures, to appear in International Journal of Robotics
Researc
Histone deacetylases as new therapy targets for platinum-resistant epithelial ovarian cancer
Introduction: In developed countries, ovarian cancer is the fourth most common cancer in women. Due to the nonspecific symptomatology associated with the disease many patients with ovarian cancer are diagnosed late, which leads to significantly poorer prognosis. Apart from surgery and radiotherapy, a substantial number of ovarian cancer patients will undergo chemotherapy and platinum based agents are the mainstream first-line therapy for this disease. Despite the initial efficacy of these therapies, many women relapse; therefore, strategies for second-line therapies are required. Regulation of DNA transcription is crucial for tumour progression, metastasis and chemoresistance which offers potential for novel drug targets. Methods: We have reviewed the existing literature on the role of histone deacetylases, nuclear enzymes regulating gene transcription. Results and conclusion: Analysis of available data suggests that a signifant proportion of drug resistance stems from abberant gene expression, therefore HDAC inhibitors are amongst the most promising therapeutic targets for cancer treatment. Together with genetic testing, they may have a potential to serve as base for patient-adapted therapies
Hedgehog-interacting protein is highly expressed in endothelial cells but down-regulated during angiogenesis and in several human tumors
BACKGROUND: The Hedgehog (Hh) signaling pathway regulates a variety of developmental processes, including vasculogenesis, and can also induce the expression of pro-angiogenic factors in fibroblasts postnatally. Misregulation of the Hh pathway has been implicated in a variety of different types of cancer, including pancreatic and small-cell lung cancer. Recently a putative antagonist of the pathway, Hedgehog-interacting protein (HIP), was identified as a Hh binding protein that is also a target of Hh signaling. We sought to clarify possible roles for HIP in angiogenesis and cancer. METHODS: Inhibition of Hh signaling by HIP was assayed by measuring the induction of Ptc-1 mRNA in TM3 cells treated with conditioned medium containing Sonic hedgehog (Shh). Angiogenesis was assayed in vitro by EC tube formation on Matrigel. Expression of HIP mRNA was assayed in cells and tissues by Q-RT-PCR and Western blot. HIP expression in human tumors or mouse xenograft tumors compared to normal tissues was assayed by Q-RT-PCR or hybridization of RNA probes to a cancer profiling array. RESULTS: We show that Hedgehog-interacting protein (HIP) is abundantly expressed in vascular endothelial cells (EC) but at low or undetectable levels in other cell types. Expression of HIP in mouse epithelial cells attenuated their response to Shh, demonstrating that HIP can antagonize Hh signaling when expressed in the responding cell, and supporting the hypothesis that HIP blocks Hh signaling in EC. HIP expression was significantly reduced in tissues undergoing angiogenesis, including PC3 human prostate cancer and A549 human lung cancer xenograft tumors, as well as in EC undergoing tube formation on Matrigel. HIP expression was also decreased in several human tumors of the liver, lung, stomach, colon and rectum when compared to the corresponding normal tissue. CONCLUSION: These results suggest that reduced expression of HIP, a naturally occurring Hh pathway antagonist, in tumor neo-vasculature may contribute to increased Hh signaling within the tumor and possibly promote angiogenesis
Uncovering novel mutational signatures by de novo extraction with SigProfilerExtractor
Mutational signature analysis is commonly performed in cancer genomic studies. Here, we present SigProfilerExtractor, an automated tool for de novo extraction of mutational signatures, and benchmark it against another 13 bioinformatics tools by using 34 scenarios encompassing 2,500 simulated signatures found in 60,000 synthetic genomes and 20,000 synthetic exomes. For simulations with 5% noise, reflecting high-quality datasets, SigProfilerExtractor outperforms other approaches by elucidating between 20% and 50% more true-positive signatures while yielding 5-fold less false-positive signatures. Applying SigProfilerExtractor to 4,643 whole-genome- and 19,184 whole-exome-sequenced cancers reveals four novel signatures. Two of the signatures are confirmed in independent cohorts, and one of these signatures is associated with tobacco smoking. In summary, this report provides a reference tool for analysis of mutational signatures, a comprehensive benchmarking of bioinformatics tools for extracting signatures, and several novel mutational signatures, including one putatively attributed to direct tobacco smoking mutagenesis in bladder tissues
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