Comparative evaluation of serologic tests for celiac disease: a European initiative toward standardization.

BACKGROUND: Serologic methods have been used widely to test for celiac disease and have gained importance in diagnostic definition and in new epidemiologic findings. However, there is no standardization, and there are no reference protocols and materials. METHODS: The European working group on Serological Screening for Celiac Disease has defined robust noncommercial test protocols for immunoglobulin (Ig)G and IgA gliadin antibodies and for IgA autoantibodies against endomysium and tissue transglutaminase. Standard curves were linear in the decisive range, and intra-assay variation coefficients were less than 5% to 10%. Calibration was performed with a group reference serum. Joint cutoff limits were used. Seven laboratories took part in the final collaborative study on 252 randomized sera classified by histology (103 pediatric and adult patients with active celiac disease, 89 disease control subjects, and 60 blood donors). RESULTS: IgA autoantibodies against endomysium and tissue transglutaminase rendered superior sensitivity (90% and 93%, respectively) and specificity (99% and 95%, respectively) over IgA and IgG gliadin antibodies. Tissue transglutaminase antibody testing showed superior receiver operating characteristic performance compared with gliadin antibodies. The K values for interlaboratory reproducibility showed superiority for IgA endomysium (0.93) in comparison with tissue transglutaminase antibodies (0.83) and gliadin antibodies (0.82 for IgG, 0.62 for IgA). CONCLUSIONS: Basic criteria of standardization and quality assessment must be fulfilled by any given test protocol proposed for serologic investigation of celiac disease. The working group has produced robust test protocols and reference materials available for standardization to further improve reliability of serologic testing for celiac disease.

TRADITION AND INNOVATION: ANALYSIS AND PERFORMANCE OF SELECTED COMPOSITIONS FOR VIOLONCELLO BY HEITOR VILLA-LOBOS

Brazilian composer Heitor Villa-Lobos (1887-1959) began his musical career as a cellist. When he was only twelve years old, it became imperativeupon the sudden and untimely death of his fatherthat the young Villa-Lobos earn money as a cellist to provide financial support for his mother and sisters. Villa-Lobos's intimate relationship with the cello eventually inspired him to compose great music for this instrument. This dissertation explores both the diversity of compositional technique and the evolution of style found in the music for cello written by Villa-Lobos. The project consists of two recorded recital performances and a written document exploring and analyzing those pieces. In the study of the music of Villa-Lobos, it is of great interest to consider the music's traditional European elements in combination (or even juxtaposition) with its imaginative and sometimes wildly innovative Brazilian character. His early works were greatly influenced by European Romantic composers such as Robert Schumann, Frédéric Chopin, and the virtuoso cellist/composer David Popper (whom Villa-Lobos idolized). Later, Villa-Lobos flourished in a newfound compositional independence and moved away from Euro-romanticism and toward the folk music of his Brazilian homeland. It is intriguing to experience this transition through an exploration of his cello compositions. The works examined and performed in this dissertation project are chosen from among the extensive number of Villa-Lobos's cello compositions and are his most important works for cello with piano, cello with another instrument, and cello with orchestra. The chosen works demonstrate the evolving range and combination of characteristic elements found in Villa-Lobos's compositional repertoire.

Mechanosensitive neurons on the internal reproductive tract contribute to egg-laying-induced acetic acid attraction in Drosophila.

Selecting a suitable site to deposit their eggs is an important reproductive need of Drosophila females. Although their choosiness toward egg-laying sites is well documented, the specific neural mechanism that activates females' search for attractive egg-laying sites is not known. Here, we show that distention and contraction of females' internal reproductive tract triggered by egg delivery through the tract plays a critical role in activating such search. We found that females start to exhibit acetic acid (AA) attraction prior to depositing each egg but no attraction when they are not laying eggs. Artificially distending the reproductive tract triggers AA attraction in non-egg-laying females, whereas silencing the mechanosensitive neurons we identified that can sense the contractile status of the tract eliminates such attraction. Our work uncovers the circuit basis of an important reproductive need of Drosophila females and provides a simple model for dissecting the neural mechanism that underlies a reproductive need-induced behavioral modification.

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.

SELECTED AMERICAN VIOLIN WORKS AND THEIR EUROPEAN CONTEXT

For my dissertation, I did a study and performance of American violin works by Charles Ives, Aaron Copland, Leonard Bernstein, and John Corigliano, along with contemporaneous European works by Paul Hindemith, Bela Bartok, Igor Stravinsky, Sergei Prokofiev, and Francis Poulenc. The selected American violin works display the development of a distinctively American style and cover a significant formative period (1914-1963) of American classical music. I intend that the European works form a backdrop for setting in relief any distinctly American qualities possessed by the American works. This is because they cover a similar time period and have significant stylistic affinities and shared influences. My topic stems from a question, "What defines the American Sound?" I attempted to find the answer by looking at the time when American composers consciously searched for their identities, and declared their music to be distinctly American. I found that those distinctive qualities stemmed from three sources: folk music, jazz and hymns. Ives and Copland can be viewed as American in content for their inclusion of such elements, while Bernstein and Corigliano can also be considered as "ideologically American" for their adventurous and eclectic spirit. The simplicity derived from singing a hymn or crooning a popular song; the freedom inspired by jazz; the optimism of accepting all possibilities-these elements inform the common spirit that I found in the music of these four American composers. FIRST RECITAL Sonatafor Violin Solo Op.3112 (1924), Paul Hindemith (1895-1963) Suite Italiennefor Violin and Piano (1932), Igor Stravinsky (1882-1971) Sonatafor Violin and Piano (1963), John Corigliano (b.1938) SECOND RECITAL Second Sonatafor Violin and Piano (1914-17), Charles Ives (1874-1954) First Rhapsody for Violin and Piano (1928), Bela Bart6k (1881-1971) Violin Sonata No.1 infminor (1938-46), Sergei Prokofiev (1891-1953) THIRD RECITAL Nocturne for Violin and Piano (1926), Aaron Copland (1900-1990)Sonata for Violin and Piano, Op. 119 (1942-3, rev.1949), Francis Poulenc (1899-1963)Serenade (after Plato's "Symposium'') (1954) by Leonard Bernstein (1918-1990) The pianists were Sun Ha Yoon (Bart6k) and Grace Eunae Cho (all other repertoire).

Long-duration animal tracking in difficult lighting conditions.

High-throughput analysis of animal behavior requires software to analyze videos. Such software typically depends on the experiments' being performed in good lighting conditions, but this ideal is difficult or impossible to achieve for certain classes of experiments. Here, we describe techniques that allow long-duration positional tracking in difficult lighting conditions with strong shadows or recurring "on"/"off" changes in lighting. The latter condition will likely become increasingly common, e.g., for Drosophila due to the advent of red-shifted channel rhodopsins. The techniques enabled tracking with good accuracy in three types of experiments with difficult lighting conditions in our lab. Our technique handling shadows relies on single-animal tracking and on shadows' and flies' being accurately distinguishable by distance to the center of the arena (or a similar geometric rule); the other techniques should be broadly applicable. We implemented the techniques as extensions of the widely-used tracking software Ctrax; however, they are relatively simple, not specific to Drosophila, and could be added to other trackers as well.

The Many Faces of Paul Hindemith

The purpose of this project is to present selected violin pieces by Paul Hindemith (1895-1963) against a backdrop of the diverse styles and traditions that he integrated in his music. For this dissertation project, selected violin sonatas by Hindemith were performed in three recitals alongside pieces by other German and Austro-German composers. These recitals were also recorded for archival purposes. The first recital, performed with pianist David Ballena on December 10, 2005, in Gildenhorn Recital Hall at the University of Maryland, College Park, included Violin Sonata Op.11, No. 1 (1918) by Paul Hindemith, Sonatina in D Major, Op. 137 (1816) by Franz Schubert, and Sonata in E-flat Major, Op.18 (1887) by Richard Strauss. The second recital, performed with pianist David Ballena on May 9, 2006, in Gildenhorn Recital Hall at the University of Maryland, included Sonata in E Minor, KV 304 (1778) by Wolfgang Amadeus Mozart, Sonata in E (1935) by Paul Hindemith, Romance for Violin and Orchestra No.1 in G Major (1800-1802) by Ludwig Van Beethoven, and Sonata for Violin and Piano in A minor, Op. 105 (1851) by Robert Schumann. The third recital, performed with David Ballena and Kai-Ching Chang on November 10, 2006 in Ulrich Recital Hall at the University of Maryland, included Violin Sonata Op.12 No.1 in D Major (1798) by Ludwig Van Beethoven, Sonata for Violin and Harpsichord No.4 in C Minor BWV 1017 (1720) by J.S. Bach, and Violin Sonata Op.11 No.2 (1918) by Paul Hindemith. For each of my dissertation recitals, I picked a piece by Hindemith as the core of the program then picked pieces by other composers that have similar key, similar texture, same number of movements or similar feeling to complete my program. Although his pieces used some classical methods of composition, he added his own distinct style: extension of chromaticism; his prominent use of interval of the fourth; his chromatic alteration of diatonic scale degrees; and his non-traditional cadences. Hindemith left behind a legacy of multi-dimensional, and innovative music capable of expressing both the old and the new aesthetics.

Polish Violin Music in the 20th and 21st Century

The purpose of this dissertation is to promote Polish violin music written in the 20th and 21st Century. My recitals included many lesser-known compositions and composers which I strongly believe deserve to be better known and more often performed. The search and preparation of those pieces, for which recordings and music scores are not easily found, was a very exciting and stimulating process. Much Polish music written in the 20th and 21st Century is interesting, expressive, beautiful, and deserves to be more often performed. Performing 20th and 21st Century music opens new perspectives in two directions: musically and technically. Performer and listener are, in many cases, unbound from tonality. Composers are looking for new sonorities and exploring such performing techniques as varieties of harmonics, quarter tones, extreme dynamics, complex rhythms, and usage of a wide range of registers. An important part of Polish music is Polish folklore. The little town of Zakopane is known for Polish traditional clothing, food, architecture, dance and music. Also, most prominent Polish luthiers including Wojciech Topa, whose instrument I am playing, have been making their instruments in Zakopane. This little town in the Tatras Mountain has been an inspiration for many Polish artists including Iwaszkiewicz, Witkacy, Karłowicz, and Szymanowski. Those composers used such folklore elements as folk scales, popular tunes, and imitations of the sound of the folk band with characteristic folk dance rhythms. Other musical genres where folk elements are strongly present are the compositions dedicated to young musicians, with a specifically educational purpose. Among composers who wrote educational music were Grażyna Bacewicz, Witold Lutosławski, and Henryk Mikołaj Górecki. This approach makes the works more easily understood by young performers and, at the same time, broadens their understanding of Polish culture and prepares them for the challenges of contemporary music. This has been an exciting project for me because, on the one hand, it allowed me the challenge of performing compositions that are lesser-known and often consist of musical language new to me while, on the other, it brought me back to my roots and the country of my mother tongue.

Evaluating The Ribosomal Internal Transcribed Spacer (ITS) as a Candidate Dinoflagellate Barcode Marker

DNA barcoding offers an efficient way to determine species identification and to measure biodiversity. For dinoflagellates, an ancient alveolate group of about 2000 described extant species, DNA barcoding studies have revealed large amounts of unrecognized species diversity, most of which is not represented in culture collections. To date, two mitochondrial gene markers, Cytochrome Oxidase I (COI) and Cytochrome b oxidase (COB), have been used to assess DNA barcoding in dinoflagellates, and both failed to amplify all taxa and suffered from low resolution. Nevertheless, both genes yielded many examples of morphospecies showing cryptic speciation and morphologically distinct named species being genetically similar, highlighting the need for a common marker. For example, a large number of cultured Symbiodinium strains have neither taxonomic identification, nor a common measure of diversity that can be used to compare this genus to other dinoflagellates.

The role of cathepsin C in Papillon-Lefèvre syndrome, prepubertal periodontitis, and aggressive periodontitis

We have previously reported that loss-of-function mutations in the cathepsin C gene (CTSC) result in Papillon Lefevre syndrome, an autosomal recessive condition characterized by palmoplantar keratosis and early,onset, severe periodontitis. Others have also reported CTSC mutations in patients with severe prepubertal periodontitis, but without any skin manifestations. The possible role of CTSC variants in more common types of non-mendelian, early-onset, severe periodontitis ("aggressive periodontitis") has not been investigated. In this study, we have investigated the role of CTSC in all three conditions. We demonstrate that PLS is genetically homogeneous and the mutation spectrum that includes three novel mutations (c.386T>A/p. V129E, c.935A>G/p.Q312R, and c.1235A>G/p.Y412C) in 21 PLS families (including eight from our previous study) provides an insight into structure-function relationships of CTSC. Our data also suggest that a complete loss-of-function appears to be necessary for the manifestation of the phenotype, making it unlikely that weak CTSC mutations are a cause of aggressive periodontitis. This was confirmed by analyses of the CTSC activity in 30 subjects with aggressive periodontitis and age-sex matched controls, which demonstrated that there was no significant difference between these two groups (1,728.7 +/- SD 576.8 mu moles/mg/min vs. 1,678.7 +/- SD 527.2 mu moles/mg/min, respectively, p = 0.73). CTSC mutations were detected in only one of two families with prepubertal periodontitis; these did not form a separate functional class with respect to those observed in classical PLS. The affected individuals in the other prepubertal periodontitis family not only lacked CTSC mutations, but in addition did not share the haplotypes at the CTSC locus. These data suggest that prepubertal periodontitis is a genetically heterogeneous disease that, in some families, just represents a partially penetrant PLS. (C) 2004 Wiley-Liss, Inc.