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Gender issues, core curriculum, and statewide content standards
Get PDFThis project is a discussion of the continuing need to address gender issues while teaching core curriculum in English classes at the secondary level
Stories Told Through Music: Soprano Aria I Know that My Redeemer Liveth from Messiah and Peter and the Wolf Op. 67
Get PDFFrom the beginning of creation, people have told stories and passed them down from generation to generation. Stories come to life through all forms of communication: watching a play, listening to a podcast, or looking at a picture are just a few examples. The best stories have been written down in manuscripts, books, novels, and then sometimes eventually written into a script for a movie. But something about music makes it one of the most compelling and exciting ways to portray a story. It is one of the earliest and long-lasting forms of storytelling. Every musical work tells a story even if the composer did not intend for a piece to have a specific theme, narrative, or plot like “program” music. All musical works still share the ideas and thoughts of the composer, who is trying to connect the audience with his or her music. Music either tells a story on its own accord, causing the listener to react emotionally and interpret it in any way he or she desires, or music portrays a story in the way the composer intended. It creates an experience and emotional response that is far more frequent than the written word alone can achieve. Just like a novel has certain elements that make it great, music contains parallels that also make it a great story. The purpose of this lecture-recital is to reveal how the essentials of a story translate into musical devices, demonstrate those musical devices to the audience and show how to listen with intentionality during the performance, and assist the conductor in becoming a better music director. The focus of this document is to give clarity to the lecture portion of the recital and also to give special rehearsal considerations for the conductor while preparing the two works performed in the recital. The musical works used in this recital to help express the purpose of storytelling in music include: (1) G. F. Handel: “I Know that My Redeemer Liveth” from Messiah (soprano aria) and (2) Sergei Prokofiev: “Peter and the Wolf.” Since these works were written nearly two-hundred years apart, these pieces vary greatly in style and purpose, but they both tell a compelling story. The first chapter of this paper will describe the necessary elements for writing or telling a wonderful narrative and how composers use musical devices to convey those elements in song. It will also discuss the rise of musical division between “program music” and “absolute music” since they both started to become specifically categorized in nineteenth-century music. The next chapter will look at the transitions of musical eras and styles from Baroque to Classical to Romantic, the continued development into twentieth-century music, and how musical expression cemented new ways to tell a story. The final two chapters will examine a brief biographical history of the composers, their compositions, and a musical analysis with how the composers implemented parallels of writing a story into the score for each piece. The final chapters will also address specific rehearsal and performance considerations a conductor needs to make prior to performing these pieces
Drug Repurposing for Gastrointestinal Stromal Tumor
Get PDFDespite significant treatment advances over the past decade, metastatic gastrointestinal stromal tumor (GIST) remains largely incurable. Rare diseases, such as GIST, individually affect small groups of patients but collectively are estimated to affect 25–30 million people in the U.S. alone. Given the costs associated with the discovery, development and registration of new drugs, orphan diseases such as GIST are often not pursued by mainstream pharmaceutical companies. As a result, “drug repurposing” or “repositioning”, has emerged as an alternative to the traditional drug development process. In this study we screened 796 FDA-approved drugs and found that two of these compounds, auranofin and fludarabine phosphate, effectively and selectively inhibited the proliferation of GISTs including imatinib-resistant cells. One of the most notable drug hits, auranofin (Ridaura®), an oral, gold-containing agent approved by the FDA in 1985 for the treatment of rheumatoid arthritis (RA), was found to inhibit thioredoxin reductase (TrxR) activity and induce reactive oxygen species (ROS) production, leading to dramatic inhibition of GIST cell growth and viability. Importantly, the anti-cancer activity associated with auranofin was independent of IM resistant status, but was closely related to the endogenous and inducible levels of ROS, therefore is prior to IM response. Coupled with the fact auranofin has an established safety profile in patients, these findings suggest for the first time that auranofin may have clinical benefit for GIST patients, particularly in those suffering from imatinib-resistant and recurrent forms of this disease
In silico and in vitro drug screening identifies new therapeutic approaches for Ewing sarcoma.
Get PDFThe long-term overall survival of Ewing sarcoma (EWS) patients remains poor; less than 30% of patients with metastatic or recurrent disease survive despite aggressive combinations of chemotherapy, radiation and surgery. To identify new therapeutic options, we employed a multi-pronged approach using in silico predictions of drug activity via an integrated bioinformatics approach in parallel with an in vitro screen of FDA-approved drugs. Twenty-seven drugs and forty-six drugs were identified, respectively, to have anti-proliferative effects for EWS, including several classes of drugs in both screening approaches. Among these drugs, 30 were extensively validated as mono-therapeutic agents and 9 in 14 various combinations in vitro. Two drugs, auranofin, a thioredoxin reductase inhibitor, and ganetespib, an HSP90 inhibitor, were predicted to have anti-cancer activities in silico and were confirmed active across a panel of genetically diverse EWS cells. When given in combination, the survival rate in vivo was superior compared to auranofin or ganetespib alone. Importantly, extensive formulations, dose tolerance, and pharmacokinetics studies demonstrated that auranofin requires alternative delivery routes to achieve therapeutically effective levels of the gold compound. These combined screening approaches provide a rapid means to identify new treatment options for patients with a rare and often-fatal disease
BAC transgenic analysis reveals enhancers sufficient for Hoxa13 and neighborhood gene expression in mouse embryonic distal limbs and genital bud
Full text linkWe previously demonstrated that a ∼1 Mb domain of genes upstream of and including Hoxa13 is co-expressed in the developing mouse limbs and genitalia. A highly conserved non-coding sequence, mmA13CNS, was shown to be insufficient in transgenic mice to direct precise Hoxa13 -like expression in the limb buds or genital bud, although some LacZ expression from the transgene was reproducibly found in these tissues. In this report, we used Β -globin minimal promoter LacZ recombinant BAC transgenes encompassing mmA13CNS to identify a single critical region involved in mouse Hoxa13 -like embryonic genital bud expression. By analyzing the expression patterns of these overlapping BAC clones in transgenic mice, we show that at least two sequences remote to the HoxA cluster are required collectively to drive Hoxa13 -like expression in developing distal limbs. Given that the paralogous posterior HoxD and neighboring genes have been shown to be under the influence of long-range distal limb and genital bud enhancers, we hypothesize that both long-range enhancers have one ancestral origin, which diverged in both sequence and function after the HoxA/D cluster duplication.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73951/1/j.1525-142X.2008.00253.x.pd
Substructure in the Coma Cluster: Giants vs Dwarfs
Get PDFThe processes that form and shape galaxy clusters, such as infall, mergers
and dynamical relaxation, tend to generate distinguishable differences between
the distributions of a cluster's giant and dwarf galaxies. Thus the dynamics of
dwarf galaxies in a cluster can provide valuable insights into its dynamical
history. With this in mind, we look for differences between the spatial and
velocity distributions of giant (b18) galaxies in the Coma
cluster. Our redshift sample contains new measurements from the 2dF and WYFFOS
spectrographs, making it more complete at faint magnitudes than any previously
studied sample of Coma galaxies. It includes 745 cluster members - 452 giants
and 293 dwarfs. We find that the line-of-sight velocity distribution of the
giants is significantly non-Gaussian, but not that for the dwarfs. A battery of
statistical tests of both the spatial and localised velocity distributions of
the galaxies in our sample finds no strong evidence for differences between the
giant and dwarf populations. These results rule out the cluster as a whole
having moved significantly towards equipartition, and they are consistent with
the cluster having formed via mergers between dynamically-relaxed subclusters.Comment: 23 pages, 6 figures, to appear in Ap
Static and fatigue performance of resin injected bolts for a slip and fatigue resistant connection in FRP bridge engineering
Get PDFThis paper presents test results to evaluate the slip and fatigue performance of Resin Injected Bolted Joints (RIBJs) for pultruded Fibre Reinforced Polymer (FRP) material. The objective of the test series is to provide a robust method of connection for structural engineering that is both fatigue and slip resistant. Forty-six joints (using 23 specimens) were subjected to either static or combined static/cyclic loading at ambient room temperature. Ten specimens (five batches of two) had bolted connections without injected resin and were included to provide baseline static joint strengths. Sikadur®-30 and RenGel®-SW404 were the two cold-curing epoxy based resins used to fabricate the 13 RIBJ specimens. Testing was conducted with double lap-shear joints in accordance with modified guidance from Annex G and Annex K in standard BS EN 1090-2:2008. The specimen’s geometry was established using this British Standard and an American Society of Civil Engineers pre-standard for pultruded thin-walled structures. Rectangular plates for the lap joints were cut from either a wide flange section of size 254×254×9.53 mm or a flat sheet of 6.35 mm thickness. Bolting was with either M16 or M20 steel threaded bolts of Grade 8.8. Sixteen specimens, for eight batches of two specimens were failed in a short duration for static strength. Four RIBJ specimens had static load cycling to an assumed service load level. Three specimens out of 23 were subjected to staged static and cyclic fatigue loadings to determine stiffness changes, life-time ‘slip’ load and residual joint strength. The reported results are evaluated for slip and fatigue performance and the main finding is that resin injection shows much promise as a mechanical method of connection in pultruded FRP structures
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