Genetic manipulation of Anopheles stephensi immunity to increase plasmodium falciparum salivary gland sporozoite infection levels

Human malaria is responsible for over 700,000 deaths a year. To stay abreast of the threat posed by the parasite, a constant stream of new drugs and vector control methods are required. This study focuses on a vaccine that has the potential to protect against parasite infection, but has been hindered by developmental challenges. In malaria prevention, live, attenuated, aseptic, Plasmodium falciparum sporozoites (PfSPZ) can be administered as a highly protective vaccine. PfSPZ are produced using adult female Anopheles stephensi mosquitoes as bioreactors. Production volume and cost of a PfSPZ vaccine for malaria are expected to be directly correlated with Plasmodium falciparum infection intensity in the salivary glands. The sporogonic development of Plasmodium falciparum in A. stephensi to fully infected salivary gland stage sporozoites is dictated by the activities of several known components of the mosquito’s innate immune system. Here I report on the use of genetic technologies that have been rarely, if ever, used in Anopheles stephensi Sda500 to increase the yield of sporozoites per mosquito and enhance vaccine production. By combining the Gal4/UAS bipartite system with in vivo expression of shRNA gene silencing, activity of the IMD signaling pathway downstream effector LRIM1, an antagonist to Plasmodium development, was reduced in the midgut, fat body, and salivary glands of A. stephensi. In infection studies using P. berghei and P. falciparum these transgenic mosquitoes consistently produced significantly more salivary gland stage sporozoites than wildtype controls, with increases in P. falciparum ranging from 2.5 to 10 fold. Using Plasmodium infection assays and qRT-PCR, two novel findings were identified. First, it was shown that 14 days post Plasmodium infection, transcript abundance of the IMD immune effector genes LRIM1, TEP1 and APL1c are elevated, in the salivary glands of A. stephensi, suggesting the salivary glands may play a role in post midgut defense against the parasite. Second, a non-pathogenic IMD signaling pathway response was observed which could suggest an alternative pathway for IMD activation. The information gained from these studies has significantly increased our knowledge of Plasmodium defense in A. stephensi and moreover could significantly improve vaccine production.

CHASING THE SINGERS: THE TRANSITION OF LONG-SONG (URTYN DUU) IN POST-SOCIALIST MONGOLIA

Long-song (Urtyn duu) is a prominent Mongolian traditional folk song genre that survived throughout the socialist period (1921-1990) and throughout the political transformation of Mongolia from socialism to democratic capitalism after the Soviet Union was dismantled and terminated its aid to Mongolia in 1990. This dissertation, based on research conducted from 2006 to 2010, presents and investigates the traces of singers' stories and memories of their lives, songs, and singing, through the lens of the discourse on change and continuity in, and as, folk tradition. During the socialist period, this genre was first considered backward, and was then subtly transformed into an urban national style, with the formation of a boundary between professionalism and amateurism among long-song singers and with selective performance of certain songs and styles. This boundary was associated with politics and ideology and might be thought to have ended when the society entered its post-socialist period. However, the long-song genre continued to play a political role, with different kinds of political meaning one the one hand and only slight musical modification on the other. It was now used to present a more nostalgic and authentic new Mongolian identity in the post-socialist free market. Through my investigation, I argue that the historical transition of Mongolia encompassed not merely political or economic shifts, but also a deeper transformation that resulted in new cultural forms. Long-song provides a good case study of the complicated process of this cultural change.

The effect of collagen organization on tensile strength loss in anterior cruciate ligament grafts post-reconstruction surgery

Gemstone Team LEGS

EARLY TWENTIETH CENTURY VIOLA MUSIC FROM ENGLAND AND GERMANY: FROM POST-ROMANTICISM TO MODERNISM

In the early twentieth century, the viola began to gain status as a solo instrument with the appearance in England of the virtuosic violist Lionel Tertis. Because of a lack of music for viola at that time, such English composers as York Bowen, Arnold Bax, Ralph Vaughan Williams, Arthur Bliss and William Walton began to write viola music for Tertis. Meanwhile, in Germany, the well-known composer and virtuosic violinist and violist Paul Hindemith wrote and premiered several viola sonatas and concertos. Viola music became even more developed later with William Primrose, the legendary Scottish violist, and all the works written in the early twentieth century have remained significant in the viola literature. Although this new viola music appeared in both countries during same period, it developed along different lines in each country. Because they were under the influence of earlier periods and traditions, the English composers who associated with Tertis wrote their music in a Romantic style, with expanded harmony, various colors of sound and timbre, and lyrical melodies. Hindemith, as a composer himself, employed a more Modernist style, using atonality and angular melodies, which represented German trends at that time. I have given three recitals, of which the first two were divided between selected English music and German music. Although I originally intended to focus solely on music by Hindemith and music written for Terts, I decided that in order to give a more complete view of the national trends of those two countries, I included Rebecca Clarke's Sonata, Lachrymae by Benjamin Britten (dedicated to William Primrose), and Max Reger's Suite for Viola. Rebecca Clarke was herself a fine violist, and her sonata's Romantic style is also representative of the English trends of viola music. Lachrymae was written with a different concept and shows more modernity than had ever before occurred in England, though it still differs from the modernity of other countries. Max Reger's Suite is in a truly Romantic style, yet it is old fashioned in ways that differ not only from Wagner or Strauss, but also from English music of the period. In my last recital I wished to pay homage to Tertis, with a program consisting entirely of music written for him. For the finale, Arthur Bliss's Viola Sonata was especially chosen because it provides interesting similarities and contrasts with earlier English music in the Romantic style.

Post-1945 Danish Piano Trio Literature: A Recording Dissertation

This recording dissertation surveys post-1945 literature written for piano trio (violin, violoncello and piano) by ten Danish composers. The literature was first considered for inclusion by searching a database provided by the Danish Music Information Center (www.mic.dk). Scores were rented from the publisher Edition Wilhelm Hansen AS, or purchased from the publisher Samfundet til Udgivelse af Dansk Musik. An additional score published by Viking Musikforlag was used as well. The music was then studied and evaluated for selection. During the selection process, the following criteria were considered: 1) quality of the compositions; 2) recognition of the composers at the national or international level; 3) whether the compositions had been previously recorded; and 4) variety of compositional styles. The selected works are written by Niels Viggo Bentzon, Vagn Holmboe, Anders Koppel, Herman D. Koppel, Bent Lorentzen, Anders Nordentoft, Per Norgard, Michael Nyvang, Karl Aage Rasmussen, and Poul Rovsing Olsen. The selected compositions were practiced, rehearsed, and performed under direct supervision of the composers and other expert musicians. In order to better understand the compositional style of each composer, relevant books, articles, and recordings were researched and studied. This recording dissertation is supported by a written document. A subjective preference for program balance was exercised to determine the order of recorded works. The written document is divided into chapters defined by composer, following the order of the recorded document, which include the composers' biographies and notes referring to the recorded compositions. The recording took place at the Manzius Gaarden, Birkerod, Denmark during three sessions: July 31-August 2, 2002, March 2 and 3, 2003, and June 2-4, 2003. The music for this dissertation was recorded by the members of the Jalina Trio; Line Fredens, violin, Janne Fredens, cello and Natsuki Fukasawa, piano. Aksel Trige, a well-respected recording engineer, was engaged for the recording and editing. Additionally, a Hamburg Steinway concert grand piano was rented and a Joseph Guarnerius filius Andreas Cremona violin (1706) was provided by the Augustinus Fonden, Denmark. The cellist used her own instrument, Vuillaume of Paris (c. 1850). The expense of this recording was partially paid by generous grants from the Augustinus Fonden, the Solist Foreningen af 1921, and the Dansk Musikerforbunds Kollective Rettighedsmidler. The compositions selected for this recording dissertation are assumed to be previously unrecorded, with the exception of Poul Rovsing Olsen's Trio II.