A study of diet and health in the elderly; the gut microbiota as a source of bioactive agents

The global proportion of older persons is increasing rapidly. Diet and the intestinal microbiota independently and jointly contribute to health in the elderly. The habitual dietary patterns and functional microbiota components of elderly subjects were investigated in order to identify specific effector mechanisms. A study of the dietary intake of Irish community-dwelling elderly subjects showed that the consumption of foods high in fat and/or sugar was excessive, while consumption of dairy foods was inadequate. Elderly females typically had a more nutrient- dense diet than males and a considerable proportion of subjects, particularly males, had inadequate intakes of calcium, magnesium, vitamin D, folate, zinc and vitamin C. The association between dietary patterns, glycaemic index and cognitive function was also investigated. Elderly subjects consuming ‘prudent’ dietary patterns had better cognitive function compared to those consuming ‘Western’ dietary patterns. Furthermore, fully-adjusted regression models revealed that a high glycaemic diet was associated with poor cognitive function, demonstrating a new link between nutrition and cognition. An extensive screening study of the elderly faecal-derived microbiota was also undertaken to examine the prevalence of antimicrobial production by intestinal bacteria. A number of previously characterised bacteriocins were isolated (gassericin T, ABP-118, mutacin II, enterocin L-50 and enterocin P) in this study. Interestingly, a Lactobacillus crispatus strain was found to produce a potentially novel antimicrobial compound. Full genome sequencing of this strain revealed the presence of three loci which exhibited varying degrees of homology with the genes responsible for helveticin J production in Lb. helveticus. An additional study comparing the immunomodulatory capacity of ‘viable’ and ‘non-viable’ Bifidobacterium strains found that Bifidobacterium-fermented milks (BFMs) containing ‘non-viable’ cells could stimulate levels of IL-10 and TNF-α in a manner similar to those stimulated by BFMs containing ‘viable’ cells in vitro.

Dairy-Met: compositional metagenomic analysis of milk and cheeses

Unpasteurised milk and many cheeses contain a diverse microbiological population. These microorganisms play important roles in dairy foods and can, for example, contribute to the development of flavours and aromas, determine safety, cause spoilage or enhance the health of the consumer. It is thus important to understand thoroughly the microorganisms present in these food types. Traditional culture dependent and culture-independent methods have provided much detail regarding the microbial content of dairy foods. However, the development of next-generation DNA sequencing technologies has revolutionised our knowledge of complex microbial environments. Throughout this thesis we observe the benefits of applying these technologies to provide a detailed understanding of the bacterial content of dairy foods, including those present in milk pre- and post-pasteurisation, Irish farmhouse cheeses and commercially produced cheeses which encounter a discolouration defect, as well as to study genomic changes in microbes associated with dairy foods. Through the application of these state-of-the-art technologies we identified the presence of microorganisms not previously associated with dairy foods.

Exploring the relationship between bacteria and tumours

Accepted Version

Assessment of the immunomodulatory effects of raw/farm milk and probiotic bacteria

The overall aims of this study were to investigate the differences between raw/farm milk and pasteurised milk with respect to potential immune modifying effects following consumption and investigate the bacterial composition of raw milk compared to pasteurised milk. Furthermore, in this thesis, panels of potential probiotic bacteria from the Bifidobacterium and Lactobacillus genera were investigated. The overall bacterial composition of raw milk was compared with pasteurised milk using samples obtained from commercial milk producers around Ireland using next generation sequencing technology (454 pyrosequencing). Here the presence of previously unrecognised and diverse bacterial populations in unpasteurised cow’s milk was identified. Futhermore the bacterial content of pasteurised milk was found to be more diverse than previously thought. The global response of the adenocarcinoma cell line HT-29 to raw milk and pasteurised milk exposures were also characterised using whole genome microarray technology. Over one thousand differentially expressed genes were identified which were found to be involved in a plethora of cellular functions. Interestingly a reduction in immune related activity (e.g. Major histocompatability complex class II signalling and T and B cell proliferation) was identified in cells exposed to pasteurised milk compared with raw milk exposures. Further studies comparing human cell response to raw versus pasteurised milk was performed using peripheral blood mononuclear cells (PBMC) from healthy donors. A reduction in CD14 was identified following raw milk exposures compared with pasteurised milk and the pattern of cytokine production may indicate that gram positive bacteria in the raw milk were contributing to the differences in the cellular response to raw versus pasteurised milk. Panels of potentially probiotic bacteria (comprising of lactobacilli and bifidobacteria) were further assessed for immunomodulatory capabilities using cell culture based models. Gene expression and cytokine production were used to evaluate stimulated and unstimulated (LPS) cellular responses as well as interaction mechanisms

The Ford administration, Angola and the perception of Post-Vietnam US credibility, 1974-1976

This thesis is a study of how the Gerald Ford administration struggled to address a perceived loss of US credibility after the collapse of Vietnam, with a focus on the role of Secretary of State Henry Kissinger in the formulation, implementation and subsequent defence of US Angolan policy. By examining the immediate post-Vietnam period, this thesis shows that Vietnam had a significant impact on Kissinger’s actions on Angola, which resulted in an ill conceived covert operation in another third world conflict. In 1974, Africa was a neglected region in Cold War US foreign policy, yet the effects of the Portuguese revolution led to a rapid decolonization of its African territories, of which Angola was to become the focus of superpower competition. After South Vietnam collapsed in April 1975, Kissinger became fixated on restoring the perceived loss of US prestige, Angola provided the first opportunity to address this. Despite objections from his advisors, Kissinger methodically engineered a covert program to assist two anti-Marxist guerrilla groups in Angola. As the crisis escalated, the media discovered the operation and the Congress decided to cease all funding. A period of heated tensions ensued, resulting in Kissinger creating a new African policy to outmanoeuvre his critics publicly, while privately castigating them to foreign leaders. This thesis argues that Kissinger’s dismissal of internal dissent and opposition from the Congress was influenced by what he perceived as bureaucrats being affected by the Vietnam syndrome, and his obsession with restoring US credibility. By looking at the private and public records – as expressed in government meetings and official reports, US newspaper and television coverage and diplomatic cables – this thesis addresses the question of how the lessons of Vietnam failed to influence Kissinger’s actions in Angola, but the lessons of Angola were heavily influential in the construction of a new US-African policy.

Human intestinal microbiota and metabolites they produce in relation to host health

The aim of this thesis was to identify selected potential probiotic characteristics of Bifidobacterium longum strains isolated from human sources, and to examine these characteristics in detail using genomic and phenotypic techniques. One strain in particular Bifidobacterium longum DPC 6315 was the main focus of the thesis and this strain was used in both the manufacture of yoghurt and an animal study. In total, 38 B. longum strains, obtained from infants and adults, were assessed in vitro for the selected probiotic traits using a combined phenotypic and molecular approach. Differentiation of the 38 strains using amplified ribosomal DNA restriction analysis (ARDRA) into subspecies indicated that of the 38 bifidobacterial strains tested, 34 were designated B. longum subsp. longum and four B. longum subsp. infantis.

Ford, Carter and Cambodia: US foreign policy and the Khmer Rouge

This thesis is an investigation into the US response to the Khmer Rouge regime in Cambodia between 1974 and 1981. It argues that the US experience in the Vietnam War acted as a causal factor in the formulation of its Cambodian policy during the presidencies of Gerald Ford and Jimmy Carter. From taking power in April 1975 to their removal by the Vietnamese in January 1979, the Khmer Rouge initiated a revolution unrivalled in the 20th Century for its brutality and for the total eradication of modern society. This thesis demonstrates that the Ford administration viewed Cambodia only as it pertained to their strategy in Vietnam and, following US disengagement from Indochina all but ignored the atrocities occurring there as they instead pursued informal relations with the Khmer Rouge as a means of punishing the Vietnamese. The Carter administration formulated a foreign policy based on human rights yet failed to adequately address the genocide that occurred in Cambodia due to its temporal and regional proximity to Vietnam. Instead, this collective reluctance to reengage with the region and the resulting anti-Vietnamese attitude reinforced Brzezinski’s broader global strategy that allied the US with China in support of an independent Cambodia to further isolate Hanoi. Thus this thesis argues that the distorting impact of the Vietnam War, as well as global Cold War calculations, undermined any appreciation of the Cambodian conflict and caused both administrations to pursue policies in Cambodia that ultimately supported the Khmer Rouge regime. This project incorporates declassified material from the Ford and Carter Presidential Libraries, supplemented by the material from the National Archives and Library of Congress, and relevant newspapers and periodicals. It demonstrates that the limitations placed upon US foreign policy by their experience in the Vietnam War may be used to reveal unexplored elements in US-Cambodian relations.

REQUIRED VIOLA REPERTOIRE FOR THE PRIMROSE COMPETITION AND THE TERTIS COMPETITION

William Primrose (1903-1982) and Lionel Tertis (1876-1975) made the viola a grand instrument for public performances of solo and chamber music throughout their long and active lives characterized by a common passion for the viola. I, too, have been deeply inspired by their passion for the viola. I chose, therefore, for my doctoral performance project to feature works for viola from the required repertoire of the William Primrose and Lionel Tertis competitions of 2001 and 2003, respectively. For purposes of the performances, I divided selections from the combined repertoire for the William Primrose and Lionel Tertis competitions into three recitals. The first recital included Sonata, Opus 120, No.2 in E-flat Major (1894) by Johannes Brahms; Sonata, Opus 147 (1975) by Dmitri Shostakovich; and Sonata (1919) by Rebecca Clarke. These pieces represent standard components of the general repertoire for both the Primrose and Tertis competitions. The second recital was comprised of two works dedicated by their composers to Primrose: Lachrymae, Opus 48 (1950) by Benjamin Britten; and Concerto (1945) by Bela Bartok. The third recital included three pieces dedicated by their composers to Tertis: Sonata (1922) by Arnold Bax; Sonata in C Minor (1905) by York Bowen; and Sonata (1952) by Arthur Bliss. The goal of my preparation for these recitals was to emphasize a variety of techniques and, also, the unique timbre of the viola. For example, the works I selected emphasized high-position technique, which was not much used before the nineteenth century, and featured the lowest string (the C-string), which provides a beautifully somber and austere sonority characteristic of the viola. For these reasons, the selected works provided not only attractive and interesting pieces to study and perform but were also of educational merit.

Measurement of the differential cross section for the reaction gamman-->pi- p from deuterium.

We report a measurement of the differential cross section for the gamman-->pi- p process from the CLAS detector at Jefferson Laboratory in Hall B for photon energies between 1.0 and 3.5 GeV and pion center-of-mass (c.m.) angles (thetac.m.) between 50 degrees and 115 degrees. We confirm a previous indication of a broad enhancement around a c.m. energy ([sqrt]s) of 2.1 GeV at thetac.m.=90 degrees in the scaled differential cross section s7dsigma/dt and a rapid falloff in a center-of-mass energy region of about 400 MeV following the enhancement. Our data show an angular dependence of this enhancement as the suggested scaling region is approached for thetac.m. from 70 degrees to 105 degrees.

Emerging Infectious Disease: Host and Parasite Perspectives

Avian malaria and related haematozoa are nearly ubiquitous parasites that can impose fitness costs of variable severity and may, in some cases, cause substantial mortality in their host populations. One example of the latter, the emergence of avian malaria in the endemic avifauna of Hawaii, has become a model for understanding the consequences of human-mediated disease introduction. The drastic declines of native Hawaiian birds due to avian malaria provided the impetus for examining more closely several aspects of host-parasite interactions in this system. Host-specificity is an important character determining the extent to which a parasite may emerge. Traditional parasite classification, however, has used host information as a character in taxonomical identification, potentially obscuring the true host range of many parasites. To improve upon previous methods, I first developed molecular tools to identify parasites infecting a particular host. I then used these molecular techniques to characterize host-specificity of parasites in the genera Plasmodium and Haemoproteus. I show that parasites in the genus Plasmodium exhibit low specificity and are therefore most likely to emerge in new hosts in the future. Subsequently, I characterized the global distribution of the single lineage of P. relictum that has emerged in Hawaii. I demonstrate that this parasite has a broad host distribution worldwide, that it is likely of Old World origin and that it has been introduced to numerous islands around the world, where it may have been overlooked as a cause of decline in native birds. I also demonstrate that morphological classification of P. relictum does not capture differences among groups of parasites that appear to be reproductively isolated based on molecular evidence. Finally, I examined whether reduced immunological capacity, which has been proposed to explain the susceptibility of Hawaiian endemics, is a general feature of an "island syndrome" in isolated avifauna of the remote Pacific. I show that, over multiple time scales, changes in immune response are not uniform and that observed changes probably reflect differences in genetic diversity, parasite exposure and life history that are unique to each species.

AN EXAMINATION OF 19TH CENTURY AUSTROGERMAN VIOLIN SONATAS

For my dissertation recital project, I traced the course of the violin-piano sonata in Austro- German in the 19th century, after Beethoven. My project presented works in three general categories. First, I presented works that are frequently-played standards of the violin sonata repertoire, works by Johannes Brahms, Franz Schubert, and Robert Schumann. The Second category is works by composers better known for their other compositions: Felix Mendelssohn and Richard Strauss. Finally, I choose the works seldom played these days, but worth of consideration, by Carl Maria von Weber and Max Reger. For my first recital, I performed Schubert's Violin Sonata, No. 1, Op. 137 in D major, Schumann's Violin Sonata, No. 1, Op. 105 in a minor, and Brahms' Violin Sonata, No.3, Op. 108 in d minor, with Naoko Takao as pianist. My second recital included works of Weber's Sonata, No. 1, Op. lob, in F major, Mendelssohn's Sonata, in F major (1838), and Schumann's Sonata, No.Z,Op.121 in d minor with Grace Cho. I concluded my final recital with the works of Reger's Violin Sonata, No. 1, Op. 1 in d minor and Strauss' Violin Sonata, Op. 18 in E flat major, Soo-Young Jung at the piano. All three programs are documented in a digital audio format available on compact disc, with accompanying programs also available in digital format.

DEGENERATE MUSIC?! MUSICAL CENSORSHIP IN THE THIRD REICH

In 1938, in Düsseldorf, the Nazis put on an exhibit entitled "Entartete Musik” (degenerate music), which included composers on the basis of their “racial origins” (i.e. Jews), or because of the “modernist style” of their music. Performance, publication, broadcast, or sale of music by composers deemed “degenerate” was forbidden by law throughout the Third Reich. Among these composers were some of the most prominent composers of the first half of the twentieth-century. They included Stravinsky, Schoenberg, Webern, Berg, Mahler, Ernst Krenek, George Gershwin, Kurt Weill, Erwin Schulhoff, and others. The music of nineteenth-century composers of Jewish origin, such as Mendelssohn and Meyerbeer, was also officially proscribed. In each of the three recitals for this project, significant works were performed by composers who were included in this exhibition, namely, Mendelssohn, Webern, Berg, Weill, and Hans Gal. In addition, as an example of self-censorship, a work of Karl Amadeus Hartmann was included. Hartmann chose “internal exile” by refusing to allow performance of his works in Germany during the Nazi regime. One notable exception to the above categories was a work by Beethoven that was presented as a bellwether of the relationship between music and politics. The range of styles and genres in these three recitals indicates the degree to which Nazi musical censorship cut a wide swath across Europe’s musical life with devastating consequences for its music and culture.

LIONEL TERTIS AND THE FLOWERING OF EARLY TWENTIETH CENTURY ENGLISH VIOLA REPERTOIRE

This performance project focused on English viola literature written in the first half of the twentieth century. During this time, numerous English composers were influenced by Lionel Tertis' unprecedented approach to the viola as a virtuosic and solo instrument. In addition to being an inspiration to composers of whom he was not in direct contact, Tertis' innovative vision for the viola led to numerous collaborations with prominent English composers of his generation. Ralph Vaughan Williams, Arnold Bax, York Bowen, Frank Bridge, Benjamin Britten, and Rebecca Clarke -his own protégé - composed some of the most important works for viola thus directly shaping the impression of the instrument as we know it today. Tertis' artistry as a performing violist was unmatched at the beginning of the twentieth century. He had a unique approach to the instrument which focused on concept of sound, tone color, concentrated listening, continuous vibrato, discreet portamento, and expressive interpretation. His convincing musical and technical ideas led him to write a treatise about how to achieve a beautiful tone. His passion for teaching and concern for the viola's posterity greatly enhanced the development of the viola. Tertis transcribed, edited, and premiered many works during his career. The music that Lionel Tertis influenced can be seen as a microcosm for a musical resurgence in England during the first half of the twentieth-century. The catalyst for this was artistic influences in the form of nationalism, folk music, romanticism, modernism, and impressionism, among others. Before this, England was widely referred to as ''the land without music" but in a very real sense, .Lionel Tertis was one of the pioneers who, through his artistry of the viola, led the way to the renaissance of music in England in the twentieth century.

IN SEARCH OF THE DIVINE: SPIRITUALITY AND PRAYER IN DIVERSE VIOLIN REPERTOIRE FROM BIBER TO IVES

Composers from all eras and of all ethnicities explore spirituality and prayer by using one or a combination of the following ideas: having a spiritual concept in mind when composing certain pieces, quoting hymns, being influenced by their own personal beliefs, or portraying spiritual figures and ideas in their works. Some musical works are inspired by spirituality; others, as in the case of Bloch's Nigun, even serve as prayers themselves. These recitals gave me the opportunity to approach a wide variety of musical styles while discovering my own mode for expression. The unaccompanied violin works throughout this project trace a distinct lineage from the baroque to the twentieth century. Biber's appendix to the Rosary Sonatas, the Passacaglia for solo violin, is a crucial predecessor to Bach's monumental Chaconne. Eugene Ysaye was inspired to write the Six Sonatas, Op. 27 after he attended a performance of Bach's Sonatas and Partitas given by Josef Szigeti. Ysaye's second solo sonata blatantly quotes Bach's Partita No.3 in E major throughout the first movement. Every movement also contains quotations from and variations on the plainchant Dies Irae. Although each of the solo violin works presented in this project may be viewed as virtuosic concert pieces, each piece allows the performer to transcend the technical hurdles-and perhaps even utilize them-to serve a higher, artistic and spiritual purpose while alone on the concert stage. Each of the sonata works in this project requires a close, equal collaboration between violinist and pianist, rather than displaying the violinist as soloist.

VARIATION FORMS: A SURVEY THROUGH FOUR CENTURIES OF VIOLIN REPERTOIRE

Variation, or the re-working of existing musical material, has consistently attracted the attention of composers and performers throughout the history of Western music. In three recorded recitals at the University of Maryland School of Music, this dissertation project explores a diverse range of expressive possibilities for violin in seven types of variation form in Austro-German works for violin from the 17th through the 20th centuries. The first program, consisting of Baroque Period works, performed on period instrument, includes the divisions on “John come kiss me now” from The Division Violin by Thomas Baltzar (1631 – 1663), constant bass variations in Sonate Unarum Fidium by Johann Heinrich von Schmelzer (1623 – 1680), arbitrary variation in Sonata for Violin and Continuo in E Major, Op. 1, No. 12 “Roger” by George Friedrich Händel (1685 – 1759), and French Double style, melodic-outline variation in Partita for Unaccompanied Violin in B Minor by Johan Sebastian Bach (1685 – 1750). Theme and Variations, a popular Classical Period format, is represented by the Sonata for Piano and Violin in G Major K. 379 by Wolfgang Amadeus Mozart (1756 – 1791) and Sonata for Violin and Piano in A Major, Op. 47 No. 9 the “Kreutzer” by Ludwig van Beethoven (1770 – 1827). Fantasy for Piano and Violin in C Major D. 934 by Franz Schubert (1797 – 1828) represents the 19th century fantasia variation. In these pieces, the piano and violin parts are densely interwoven, having equal importance. Many 20th century composers incorporated diverse types of variations in their works and are represented in the third recital program comprising: serial variation in the Phantasy for Violin and Piano Op.47 of Arnold Schoenberg (1874 – 1951); a strict form of melodic-outline variation in Sonate für Violine allein, Op. 31, No. 2 of Paul Hindemith (1895 – 1963); ostinato variation in Johan Halvorsen’s (1864 – 1935) Passacaglia for Violin and Viola, after G. F. Handel’s Passacaglia from the Harpsichord Suite No. 7 in G Minor. Pianist Audrey Andrist, harpsichordist Sooyoung Jung, and violist Dong-Wook Kim assisted in these performances.