Genome-wide scan of copy number variation in late-onset Alzheimer's disease.

Alzheimer's disease is a complex and progressive neurodegenerative disease leading to loss of memory, cognitive impairment, and ultimately death. To date, six large-scale genome-wide association studies have been conducted to identify SNPs that influence disease predisposition. These studies have confirmed the well-known APOE epsilon4 risk allele, identified a novel variant that influences disease risk within the APOE epsilon4 population, found a SNP that modifies the age of disease onset, as well as reported the first sex-linked susceptibility variant. Here we report a genome-wide scan of Alzheimer's disease in a set of 331 cases and 368 controls, extending analyses for the first time to include assessments of copy number variation. In this analysis, no new SNPs show genome-wide significance. We also screened for effects of copy number variation, and while nothing was significant, a duplication in CHRNA7 appears interesting enough to warrant further investigation.

North atlantic deepwater temperature change during late pliocene and late quaternary climatic cycles

Variations in the ratio of magnesium to calcium (Mg/Ca) in fossil ostracodes from Deep Sea Drilling Project Site 607 in the deep North Atlantic show that the change in bottom water temperature during late Pliocene 41,000-year obliquity cycles averaged 1.5°C between 3.2 and 2.8 million years ago (Ma) and increased to 2.3°C between 2.8 and 2.3 Ma, coincidentally with the intensification of Northern Hemisphere glaciation. During the last two 100,000-year glacial-to-interglacial climatic cycles of the Quaternary, bottom water temperatures changed by 4.5°C. These results show that glacial deepwater cooling has intensified since 3.2 Ma, most likely as the result of progressively diminished deep-water production in the North Atlantic and of the greater influence of Antarctic bottom water in the North Atlantic during glacial periods. The ostracode Mg/Ca data also allow the direct determination of the temperature component of the benthic foraminiferal oxygen isotope record from Site 607, as well as derivation of a hypothetical sea-level curve for the late Pliocene and late Quaternary. The effects of dissolution on the Mg/Ca ratios of ostracode shells appear to have been minimal.

CONSERVATIVE AND PROGFESSIVE ASPECTS OF THE SONATA FROM LATE BEETHOVEN TO PROKOFIEV

The term 'sonata' arose in the early seventeenth-century Baroque period and was originally used to distinguish instrumental (sonata) music from vocal music. Later. the sonata style, as a reliable yet flexible compositional framework, was extensively shaped and utilized throughout the Classical period. Subsequently, in the Romantic period, freer creative, individualistic. and expressive musical elements began to be preferred by composers in their use of harmonj., tone color, form, and rhythm. However, even during the revolutionary Romantic period in music. the compositions which did not have a pre-defined format (character pieces, etc) were often comfortably framed and limited within the recognizable boundaries provided by the Classical sonata style. The sonata format, when used as a tool in musical composition, provides logical boundaries that may serve to organize any unexpected emotional expressions on the part of the composer. Yet the sonata framework is also flexible enough to allow freedom of expression. In the Romantic period and beyond, composers had relied, some more than others, upon the sonata's adaptable blend of stability and flexibility. In my opinion, it is more persuasive to express oneself musically within the framework of an established musical style. Thus, I have chosen my dissertation topic as the performance of six pieces incorporating elements of the reliable and flexible sonata style. The sonata of each composer that I have selected clearly demonstrates a tension between logic and emotion expressed within the sonata framework. However, the compositions can be divided interestingly into two groups, such as 'conservative' and 'progressive' group. The 'conservative' group consists of composers who seemed to strive for greater freedom of self-expression within the constraints of the traditional sonata form. On the other hand, the 'progressive' group consists of composers who seemed more to rely upon the sonata form to rein in and add stability to their highly individual and emotional musical ideas. It is my hope that this project will provide a stimulating viewpoint from which to consider the evolution and utilization of the sonata style especially as it is applied to the composition and performance of these six diverse and interesting pieces.

VERSATILITY IN THE MODERN PERFORMER: THREE DIVERSE OPERA ROLES

This dissertation project consisted of performances of three diverse operatic roles. The goal was to examine the challenges and benefits of performing diverse repertoire (baroque, classical, and romantic opera, in this case) and to observe how vocal and acting techniques might adjust to different styles and voice classifications. On December 3, 5, 11, and 13,2003, I performed a composite role in Fatal Song, directed by Leon Major, in the Robert & Arlene Kogod Theatre. This opera pastiche, premiered in 1996, contains spoken dialogue, and the music originates from famous eighteenth and nineteenth-century operas. I explored the challenges and benefits of playing three different, well-known opera characters within the same opera, performing four different languages within the same opera, and performing spoken dialogue in an opera. My roles in this pastiche of famous opera included Lucia from Lucia di Lammermoor by Gaetano Donizetti, Manon from Manon by Jules Massenet, and Pamina from Die ZauberJlote by W.A. Mozart. On January 28 and 29, 2005, I performed the role of Nice in Eurilla e Alcindo, a serenata by Antonio Vivaldi, in Homer Ulrich Recital Hall; musical direction by Joseph Gascho and stage direction by Kate Vetter Cain. I explored the challenges and benefits of preparing baroque ornamentation, singing without a conductor, performing an unknown work, staging a work that is not traditionally staged, singing with minimal sets and costumes, and singing with period instruments. On April 16,20, and 24,2005, I performed the role of Musetta in Giacomo Puccini's La BohBme, directed by Pat Diamond and conducted by Jeffrey Rink, in the Ina & Jack Kay Theatre. I examined the challenges and benefits of singing with a large orchestra of modem instruments, singing Puccini rubato and coordinating this with the conductor, and singing a role in one of the most well-known operas in today's repertoire. As a result of this investigation, I concluded that singing different styles, and singing outside one's voice classification, within reason, is beneficial. The knowledge, skill, confidence and insight I acquired by becoming more versatile benefited me as a performer and as a teacher.

TWENTIETH CENTURY VARIATIONS ON BORROWED THEMES

Mergers and acquisitions are words that are usually associated with the modern business world. Such joint efforts toward improvement, however, existed long before our time, in the form of musical partnerships. It was not unusual for composers to share in each other's works, borrowing themes and recreating them to generate new meanings; in the process, new masterpieces were often created. My performance project, Twentieth Century Variations on Borrowed Themes, explores the fruits of such labor. The main objective of this project is to demonstrate how certain composers of the twentieth century have taken famous themes and used them to create variations, imbuing their own creative ideas, musical styles and pianistic challenges. This objective was accomplished by performing three recorded public recitals. These programs consisted of early to late twentieth century pieces that are based on borrowed themes, either in theme and variations form, fantasia form, paraphrase form, or transformal variation form. I have selected the pieces based on their artistic merits and technical challenges, thus allowing me to grow as a pianist and artist. In addition, I wanted to choose some pieces that are rarely performed, as I believe the public delights in hearing unfamiliar gems. The first recital consisted of the music of two legendary pianists: Variations on a Theme of Chopin by Rachmaninoff and Goldberg Variations by BachIBusoni. The second program featured Grand Fantasy on Gershwin's Porgy and Bess by Earl Wild, Sonatina No. 6 (Fantasy on Bizet 's "Carmen") by Busoni, and Rhapsody on a Theme by Paganini, op.43 by Rachmaninoff. Some unusual and seldom-performed pieces, as well as a familiar favorite, were spotlighted in the third recital. The pieces performed on this program were John Rea's Twenty-one Transformal Variations on the "Kindersznen " by Robert Schumann (Las Meninas), Muczynski's Desperate Measures (Paganini Variations), Busoni's Elegie No. 3 (Turandot 's room), and Rhapsodie Espagnole by LisztIBuson. These composers artfully breathed new life into the material borrowed from others, and in the process, the "borrowed" themes became undoubtedly and uniquely their own music.

Making it in the Modern Job Market: A Study of Communication among the Deaf and Hard of Hearing Population

Gemstone Team AUDIO (Assessing and Understanding Deaf Individuals' Occupations)

Three Hundred Years in Annapolis: Phase III Archaeological Investigations of the Anne Arundel County Courthouse Site (18AP63), Annapolis, Maryland

During the summer of 1994, Archaeology in Annapolis conducted archaeological investigations of the city block bounded by Franklin, South and Cathedral Streets in the city of Annapolis. This Phase III excavation was conducted as a means to identify subsurface cultural resources in the impact area associated with the proposed construction of the Anne Arundel County Courthouse addition. This impact area included both the upper and lower parking lots used by Courthouse employees. Investigations were conducted in the form of mechanical trenching and hand excavated units. Excavations in the upper lot area yielded significant information concerning the interior area of the block. Known as Bellis Court, this series of rowhouses was constructed in the late nineteenth century and was used as rental properties by African-Americans. The dwellings remained until the middle of the twentieth century when they were demolished in preparation for the construction of a Courthouse addition. Portions of the foundation of a house owned by William H. Bellis in the 1870s were also exposed in this area. Construction of this house was begun by William Nicholson around 1730 and completed by Daniel Dulany in 1732/33. It was demolished in 1896 by James Munroe, a Trustee for Bellis. Excavations in the upper lot also revealed the remains of a late seventeenth/early eighteenth century wood-lined cellar, believed to be part of the earliest known structure on Lot 58. After an initially rapid deposition of fill around 1828, this cellar was gradually covered with soil throughout the remainder of the nineteenth century. The fill deposit in the cellar feature yielded a mixed assemblage of artifacts that included sherds of early materials such as North Devon gravel-tempered earthenware, North Devon sgraffito and Northem Italian slipware, along with creamware, pearlware and whiteware. In the lower parking lot, numerous artifacts were recovered from yard scatter associated with the houses that at one time fronted along Cathedral Street and were occupied by African- Americans. An assemblage of late seventeenth century/early eighteenth century materials and several slag deposits from an early forge were recovered from this second area of study. The materials associated with the forge, including portions of a crucible, provided evidence of some of the earliest industry in Annapolis. Investigations in both the upper and lower parking lots added to the knowledge of the changing landscape within the project area, including a prevalence of open space in early periods, a surprising survival of impermanent structures, and a gradual regrading and filling of the block with houses and interior courts. Excavations at the Anne Arundel County Courthouse proved this to be a multi-component site, rich in cultural resources from Annapolis' Early Settlement Period through its Modern Period (as specified by Maryland's Comprehensive Historic Preservation Plan (Weissman 1986)). This report provides detailed interpretations of the archaeological findings of these Phase III investigations.

Caring for Alaska Native prostate cancer survivors in primary care: a survey of Alaska Tribal Health System providers.

BACKGROUND: Little is known about the constraints of optimizing health care for prostate cancer survivors in Alaska primary care. OBJECTIVE: To describe the experiences and attitudes of primary care providers within the Alaska Tribal Health System (ATHS) regarding the care of prostate cancer survivors. DESIGN: In late October 2011, we emailed a 22-item electronic survey to 268 ATHS primary care providers regarding the frequency of Prostate Specific Antigen (PSA) monitoring for a hypothetical prostate cancer survivor; who should be responsible for the patient's life-long prostate cancer surveillance; who should support the patient's emotional and medical needs as a survivor; and providers' level of comfort addressing recurrence monitoring, erectile dysfunction, urinary incontinence, androgen deprivation therapy, and emotional needs. We used simple logistic regression to examine the association between provider characteristics and their responses to the survivorship survey items. RESULTS: Of 221 individuals who were successfully contacted, a total of 114 responded (52% response rate). Most ATHS providers indicated they would order a PSA test every 12 months (69%) and believed that, ideally, the hypothetical patient's primary care provider should be responsible for his life-long prostate cancer surveillance (60%). Most providers reported feeling either "moderately" or "very" comfortable addressing topics such as prostate cancer recurrence (59%), erectile dysfunction (64%), urinary incontinence (63%), and emotional needs (61%) with prostate cancer survivors. These results varied somewhat by provider characteristics including female sex, years in practice, and the number of prostate cancer survivors seen in their practice. CONCLUSIONS: These data suggest that most primary care providers in Alaska are poised to assume the care of prostate cancer survivors locally. However, we also found that large minorities of providers do not feel confident in their ability to manage common issues in prostate cancer survivorship, implying that continued access to specialists with more expert knowledge would be beneficial.

BOULANGER, SATIE, AND DEBUSSY: THEIR SPHERES OF INFLUENCE ON FRENCH MELODIE AND AMERICAN ART SONG

This dissertation project explored the spheres of influence on art song by Nadia Boulanger, Erik Satie, and Claude Debussy within Boulangeries, Les Six, and Les Apaches. After World War I, American composers flocked to Paris to study with Boulanger. Boulanger gave her students the confidence to explore their native talents instead of mimicking foreign models. Works by Aaron Copland, Virgil Thomson, Theodore Chanler, John Duke, and Richard Hundley were included in the first dissertation recital on January 31, 2010: The Legacy of Nadia Boulanger: Her Influence on American Song Composers. Satie established a new modern French musical style, and was a catalyst for the formation of Les Six. Ned Rorem came to Paris, and had a close association with Les Six. Works by Satie, and three members of Les Six, Francis Poulenc, Arthur Honegger, Darius Milhaud; and Rorem were featured in the second recital on September 1, 2010: Satie, Selected Members of Les Six, and Rorem in Paris. Debussy was one of the most significant French composers in the late nineteenth century, predating Boulanger and Satie. Young composers exploring new directions were inspired by Debussy, forming the group Les Apaches. The final recital, April 7, 2011, featured works by Debussy and two members of Les Apaches, Maurice Ravel and Manuel de Falla: Debussy: A Catalyst for Les Apaches, Ravel and Falla. Falla‘s less well-known repertoire was presented. This dissertation showed the influence of these three major figures and that they embraced innovation in their own time, along with their followers. Recordings of these three performances may be obtained from the Michelle Smith Performing Arts Library in Clarice Smith Performing Arts Center at the University of Maryland, College Park.

FROM THE AETHIOPICA TO THE RENAISSANCE: RECOVERING A STAGE TRADITION OF POSITIVE REPRESENTATION OF AFRICANS IN EARLY MODERN ENGLAND

This dissertation looks at the connection between Heliodorus's fifth-century prose romance, An Aethiopian History, certain Renaissance texts, and how these texts helped influence an alternate representation of Africans in the early modern world. Through their portrayals of Africans, early modern English playwrights frequently give the impression that Africans, especially black Africans, were people without accomplishments, without culture. Previously, however, this was not the case. Africans were depicted with dignity, as a tradition existed for this kind of representation--and Renaissance Europe had long been acquainted with the achievements of Africans, dating back to antiquity. As the source of several lost plays, the Aethiopica is instrumental in dramatizing Africans favorably, especially on the early modern stage, and helped shape a stage tradition that runs alongside the stereotyping of Africans. This Heliodoran tradition can be seen in works of Greene, Heywood, Jonson, Shakespeare, and others in the motifs of crosscultural and transracial romance, male and female chastity, racial metamorphosis, lost or abandoned babies, wandering heroes, and bold heroines. In Jonson's Masque of Blackness and Masque of Beauty, I establish a connection between these two masques and Heliodorus's Aethiopica and argue for a Heliodoran stage tradition implicit in both masques through the conceit of blanching. In The English Moore, I explore how Richard Brome uses the Heliodoran and Jonsonian materials to create a negative quality of blackness that participates in the dramatic tradition of the degenerate African on the English Renaissance stage. With Othello, I contend that it is a drama that can be seen in the Heliodoran tradition by stressing certain motifs found in the play that derives from the Aethiopica. Reading Othello this way provides us with a more layered and historicized interpretation of Shakespeare's protagonists. Othello's nationality and faith make his exalted position in Venice and the Venetian army credible and logical. His nobility and heroic status become more sharply defined, giving us a fuller understanding of the emphasis he places on chastity--both for himself and for Desdemona. Instead of a traditional, compliant, and submissive Desdemona, a courageous, resourceful, witty, and pure heroine emerges--one who lives by the dictates of her conscience than by the constraints of societal norms. Recovering the tradition of positive portrayal of Africans that originated from the Aethiopica necessitated an examination of eleven plays that I contend helped to frame the dramatic tradition under investigation. Six of these plays are continental dramas, and five are English. Although three of the English plays are lost and the other two are seventeenth-century dramas, their titles and names of their protagonists, like those of the six extant continental plays, share the names of Heliodorus's hero and heroine, making an exploration of the continental plays imperative to facilitate their use as paradigms in reconstructing the three lost English plays. These continental dramas show that plays whose titles derive from the Aethiopica itself or reflect the names of its major characters follow Heliodorus's text closely, enabling an investigation of the Heliodoran tradition on the early modern English stage. Recovering the Heliodoran tradition adds to the exploration of racial politics and the understanding of the dramatic tradition that constrained and enabled Renaissance playwrights' representation of race and gender.

Identification of late larval stage developmental checkpoints in Caenorhabditis elegans regulated by insulin/IGF and steroid hormone signaling pathways.

Organisms in the wild develop with varying food availability. During periods of nutritional scarcity, development may slow or arrest until conditions improve. The ability to modulate developmental programs in response to poor nutritional conditions requires a means of sensing the changing nutritional environment and limiting tissue growth. The mechanisms by which organisms accomplish this adaptation are not well understood. We sought to study this question by examining the effects of nutrient deprivation on Caenorhabditis elegans development during the late larval stages, L3 and L4, a period of extensive tissue growth and morphogenesis. By removing animals from food at different times, we show here that specific checkpoints exist in the early L3 and early L4 stages that systemically arrest the development of diverse tissues and cellular processes. These checkpoints occur once in each larval stage after molting and prior to initiation of the subsequent molting cycle. DAF-2, the insulin/insulin-like growth factor receptor, regulates passage through the L3 and L4 checkpoints in response to nutrition. The FOXO transcription factor DAF-16, a major target of insulin-like signaling, functions cell-nonautonomously in the hypodermis (skin) to arrest developmental upon nutrient removal. The effects of DAF-16 on progression through the L3 and L4 stages are mediated by DAF-9, a cytochrome P450 ortholog involved in the production of C. elegans steroid hormones. Our results identify a novel mode of C. elegans growth in which development progresses from one checkpoint to the next. At each checkpoint, nutritional conditions determine whether animals remain arrested or continue development to the next checkpoint.

New World Gold Cultural Anxiety and Monetary Disorder in Early Modern Spain

Elvira Vilches examines economic treatises, stories of travel and conquest, moralist writings, fiction, poetry, and drama to reveal that New World gold ultimately became a problematic source of power that destabilized Spain’s sense of ...

No association between TGFB1 polymorphisms and late radiotherapy toxicity: a meta-analysis.

BACKGROUND: Transforming growth factor-beta 1 (TGF-β1) protein may be multifunctional and related to the development of fibrosis, induction of apoptosis, extracellular signaling and inhibition of proliferation in response to radiation-induced DNA damage. Several studies have investigated associations between single nucleotide polymorphisms (SNPs) in the TGFB1 gene and risk of late radiation-induced injury of normal tissue, but the conclusions remain controversial. METHODS: We searched three electronic databases (i.e., MEDLINE, EMBASE and EBSCO) for eligible publications and performed a meta-analysis assessing the association of three commonly studied SNPs in TGFB1 (i.e., rs1800469, rs1800470 and rs1800471) with risk of late radiation-induced injury of normal tissue. RESULTS: We finally included 28 case-only studies from 16 publications on aforementioned SNPs in TGFB1. However, we did not find statistical evidence of any significant association with overall risk of late radiotherapy toxicity in the pooled analysis or in further stratified analysis by cancer type, endpoint, ethnicity and sample size. CONCLUSIONS: This meta-analysis did not find statistical evidence for an association between SNPs in TGFB1 and risk of late radiation-induced injury of normal tissue, but this finding needs further confirmation by a single large study.

TEACHING AMERICAN CIVIL WAR MUSIC IDSTORY WITH MODERN EDITIONS OF PERIOD MUSIC FOR FULL CONCERT BAND

This dissertation explores a method of teaching the history of Civil War music and musicians through modern full-band editions of original brass band music. In the study of music history the period of the Civil War is rarely discussed, or at best, mentioned only if a student takes a specific course on the history of bands and happens to look deeply into the background of some of the early band pioneers such as Patrick Gilmore, who served in the Union Army as a bandmaster. The history of the musicians, bands, and music performed during the Civil War deserves study to provide a way for students and audiences to learn this history. This project includes lesson plans that can be used with the arrangements of the period music as well as select published music that is also representative of the period. Included with the historical information are four arrangements of original brass band music now scored for full concert band. Each arrangement includes a section scored for brass only with optional brass band parts. Historical information is provided on the Civil War period bands and how each side used them, on the composers of the music, and also on the individual compositions. The historical information can be used to supplement the lesson plans to teach the history, as well as for program notes for audiences. The research involved locating information on both Union and Confederate bands available in books, other dissertations, articles, and interviews with Civil War music historians. The original brass band music is scored for full band. This method will allow teachers and conductors to highlight this period of wind band history and to share it with both students and audiences. Included with this project are photos and video footage taken during a visit with the 1st Brigade Band of Watertown, Wisconsin, an historical organization dedicated to recreating the music and performances of an actual Civil War era band.