Synthesis and reactivity of α-diazosulfoxide and α-diazosulfone derivatives

The research described in this thesis involves the synthesis of α-diazo-β-oxo sulfoxides, and exploration of their reactivity. The first chapter includes an introduction to diazocarbonyl chemistry, specifically focusing on the synthesis of diazo compounds, and diazosulfoxide derivatives. The chemistry of sulfines, in particular the generation of α-oxo sulfines and their subsequent trapping as cycloadducts and dimerisation is discussed. The results of this research are discussed in the second and third chapters. The design, synthesis and reactivity of α-diazo-β-oxo sulfoxides is described in chapter 2 where diazo transfer adjacent to sulfoxides to form stable α-diazo-β-oxo sulfoxides has been achieved in cyclic systems. Decomposition of theses α-diazosulfoxides using rhodium carboxylate or carboxamide catalysts is also described. These processes proceed via a Wolff type rearrangement to form α-oxo sulfine intermediates, which were trapped as cycloadducts with dienes. In the absence of a diene trap, dimerisation of the sulfine intermediate was observed. Intramolecular C-H insertion reasctios of α-diazo-α-sulfonyl esters to form substituted sulfolane esters is described in chapter 3. The reactivity of these sulfolane esters is briefly explored. The fourth chapter contains the experimental details and the spectral and analytical data for all new compounds reported.

Taming hazardous chemistry in flow: The continuous processing of diazo and diazonium compounds

The synthetic utilities of the diazo and diazonium groups are matched only by their reputation for explosive decomposition. Continuous processing technology offers new opportunities to make and use these versatile intermediates at a range of scales with improved safety over traditional batch processes. In this minireview, the state of the art in the continuous flow processing of reactive diazo and diazonium species is discussed.

Das Bistum Würzburg 7. Die Würzburger Bischöfe von 1617 bis 1684

Winfried Romberg führt mit dem Band Die Würzburger Bischöfe von 1617 bis 1684 die Bischofsreihe fort, die Alfred Wendehorst begonnen hat (Germania Sacra Neue Folge 1/4/13). Damit erscheint ein Band, der in besonderer Weise für den Schwerpunkt der Dritten Folge der Germania Sacra steht: Die Darstellung von Diözesen und Domkapiteln der Kirche des Alten Reiches. Er beleuchtet die Lebensläufe und Amtstätigkeiten neuzeitlicher Würzburger Bischöfe des 17. Jahrhunderts und umfasst die Pontifikate von Johann Gottfried I. von Aschhausen (1617–1622) bis zum Pontifikat von Konrad Wilhelm von Wernau (1683–1684). Die Bischöfe dieser Zeit waren von überregionaler Bedeutung und Wirksamkeit, wie sich beispielhaft in der Person des Bischofs Johann Philipp I. von Schönborn (1642–1673) zeigt, der zugleich Erzbischof von Mainz war. Johann Gottfried I. von Aschhausen, Franz von Hatzfeld und Peter Philipp von Dernbach waren Bischöfe von Würzburg und Bamberg in Personalunion, womit sich der Band auch an die Darstellung der Bamberger Bischofsreihe von 1522 bis 1693 von Dieter J. Weiß (Germania Sacra Neue Folge 38) anschließt. Die Viten, die das Wirken des einzelnen Bischofs in seinem Amt in den Vordergrund stellen, bewegen sich im geschichtsträchtigen Umfeld von Rekatholisierung, Dreißigjährigem Krieg und Frühabsolutismus.

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.

Can metaphors and analogies improve communication with seriously ill patients?

OBJECTIVE: It is not known how often physicians use metaphors and analogies, or whether they improve patients' perceptions of their physicians' ability to communicate effectively. Therefore, the objective of this study was to determine whether the use of metaphors and analogies in difficult conversations is associated with better patient ratings of their physicians' communication skills. DESIGN: Cross-sectional observational study of audio-recorded conversations between patients and physicians. SETTING: Three outpatient oncology practices. PATIENTS: Ninety-four patients with advanced cancer and 52 physicians. INTERVENTION: None. MAIN OUTCOME MEASURES: Conversations were reviewed and coded for the presence of metaphors and analogies. Patients also completed a 6-item rating of their physician's ability to communicate. RESULTS: In a sample of 101 conversations, coders identified 193 metaphors and 75 analogies. Metaphors appeared in approximately twice as many conversations as analogies did (65/101, 64% versus 31/101, 31%; sign test p < 0.001). Conversations also contained more metaphors than analogies (mean 1.6, range 0-11 versus mean 0.6, range 0-5; sign rank test p < 0.001). Physicians who used more metaphors elicited better patient ratings of communication (rho = 0.27; p = 0.006), as did physicians who used more analogies (Spearman rho = 0.34; p < 0.001). CONCLUSIONS: The use of metaphors and analogies may enhance physicians' ability to communicate.

Communication practices in physician decision-making for an unstable critically ill patient with end-stage cancer.

BACKGROUND: Shared decision-making has become the standard of care for most medical treatments. However, little is known about physician communication practices in the decision making for unstable critically ill patients with known end-stage disease. OBJECTIVE: To describe communication practices of physicians making treatment decisions for unstable critically ill patients with end-stage cancer, using the framework of shared decision-making. DESIGN: Analysis of audiotaped encounters between physicians and a standardized patient, in a high-fidelity simulation scenario, to identify best practice communication behaviors. The simulation depicted a 78-year-old man with metastatic gastric cancer, life-threatening hypoxia, and stable preferences to avoid intensive care unit (ICU) admission and intubation. Blinded coders assessed the encounters for verbal communication behaviors associated with handling emotions and discussion of end-of-life goals. We calculated a score for skill at handling emotions (0-6) and at discussing end of life goals (0-16). SUBJECTS: Twenty-seven hospital-based physicians. RESULTS: Independent variables included physician demographics and communication behaviors. We used treatment decisions (ICU admission and initiation of palliation) as a proxy for accurate identification of patient preferences. Eight physicians admitted the patient to the ICU, and 16 initiated palliation. Physicians varied, but on average demonstrated low skill at handling emotions (mean, 0.7) and moderate skill at discussing end-of-life goals (mean, 7.4). We found that skill at discussing end-of-life goals was associated with initiation of palliation (p = 0.04). CONCLUSIONS: It is possible to analyze the decision making of physicians managing unstable critically ill patients with end-stage cancer using the framework of shared decision-making.

Platinum(II)-catalyzed intermolecular hydroamination of monosubstituted allenes with secondary alkylamines.

A 1:1 mixture of (dppf)PtCl(2) and AgOTf (5 mol%) catalyzed the intermolecular hydroamination of monosubstituted allenes with secondary alkylamines at 80 degrees C to form allylic amines in good yield with selective formation of the E-diastereomer.

NEGLECTED CELLO REPERTOIRE OF TWENTIETH CENTURY ENGLISH COMPOSERS

In the Twentieth Century, the proliferation of cellists and the exceptional development of cello techniques, combined with composers' acceptance of the challenges by these developments, led many British composers to contribute to the enrichment of the cello concert repertoire. A great number of compositions written for the cello in the Twentieth Century England have been long neglected. In comparison with their other works in the genres of concerto, symphony, and opera, works for cello by prominent Twentieth Century English composers Elgar, Walton, and Britten are relatively unknown, except for Elgar's cello concerto. There are also many lesser-known composers like Delius, Bax, Bridge, and Clarke, who flourished in the fmt half of the century, but eventually became disregarded. Some reasons for this neglect may be as follows: the reluctant attitude toward new trends in the English musical establishment around the turn of the century; a lack of readily available editions of these composers' compositions; an over-abundance of fine composers at one time; and lastly, an overly individualistic approach to the music restricting a general public appreciation and recognition. Encountering a recording of the Walton cello concerto prompted me to further study the neglected Twentieth Century English cello repertoire. Many works of the above-mentioned composers still have not been fully valued in the cello repertoire. For this reason, the purpose of this project was to inspire cellists to learn and broaden as well as to appreciate the beauty of the Twentieth Century cello literature. As part of the doctoral performance project, three recitals featuring the works by six English composers were performed. My collaborator in all three recitals was pianist Eunae KO. The fmt recital included the Sonata for cello and piano by Frank Bridge and the Concerto by William Walton. The second recital was comprised of relatively unknown cello works: Sonatina in D major by Arnold Bax, Romance by Frederick Delius, and the Sonata Op. 40 by Rebecca Clarke. The third recital consisted of Folk-Tale by Arnold Bax and the Symphony for Cello and Orchestra Op. 68 by Benjamin Britten.

Impacts of Mountaintop Removal Coal Mining on the Mud River, West Virginia: Selenium Accumulation, Trophic Transfer, and Toxicity in Fish

Selenium (Se) is a micronutrient necessary for the function of a variety of important enzymes; Se also exhibits a narrow range in concentrations between essentiality and toxicity. Oviparous vertebrates such as birds and fish are especially sensitive to Se toxicity, which causes reproductive impairment and defects in embryo development. Selenium occurs naturally in the Earth's crust, but it can be mobilized by a variety of anthropogenic activities, including agricultural practices, coal burning, and mining.

Mountaintop removal/valley fill (MTR/VF) coal mining is a form of surface mining found throughout central Appalachia in the United States that involves blasting off the tops of mountains to access underlying coal seams. Spoil rock from the mountain is placed into adjacent valleys, forming valley fills, which bury stream headwaters and negatively impact surface water quality. This research focused on the biological impacts of Se leached from MTR/VF coal mining operations located around the Mud River, West Virginia.

In order to assess the status of Se in a lotic (flowing) system such as the Mud River, surface water, insects, and fish samples including creek chub (Semotilus atromaculatus) and green sunfish (Lepomis cyanellus) were collected from a mining impacted site as well as from a reference site not impacted by mining. Analysis of samples from the mined site showed increased conductivity and Se in the surface waters compared to the reference site in addition to increased concentrations of Se in insects and fish. Histological analysis of mined site fish gills showed a lack of normal parasites, suggesting parasite populations may be disrupted due to poor water quality. X-ray absorption near edge spectroscopy techniques were used to determine the speciation of Se in insect and creek chub samples. Insects contained approximately 40-50% inorganic Se (selenate and selenite) and 50-60% organic Se (Se-methionine and Se-cystine) while fish tissues contained lower proportions of inorganic Se than insects, instead having higher proportions of organic Se in the forms of methyl-Se-cysteine, Se-cystine, and Se-methionine.

Otoliths, calcified inner ear structures, were also collected from Mud River creek chubs and green sunfish and analyzed for Se content using laser ablation inductively couple mass spectrometry (LA-ICP-MS). Significant differences were found between the two species of fish, based on the concentrations of otolith Se. Green sunfish otoliths from all sites contained background or low concentrations of otolith Se (< 1 µg/g) that were not significantly different between mined and unmined sites. In contrast creek chub otoliths from the historically mined site contained much higher (≥ 5 µg/g, up to approximately 68 µg/g) concentrations of Se than for the same species in the unmined site or for the green sunfish. Otolith Se concentrations were related to muscle Se concentrations for creek chubs (R2 = 0.54, p = 0.0002 for the last 20% of the otolith Se versus muscle Se) while no relationship was observed for green sunfish.

Additional experiments using biofilms grown in the Mud River showed increased Se in mined site biofilms compared to the reference site. When we fed fathead minnows (Pimephales promelas) on these biofilms in the laboratory they accumulated higher concentrations of Se in liver and ovary tissues compared to fathead minnows fed on reference site biofilms. No differences in Se accumulation were found in muscle from either treatment group. Biofilms were also centrifuged and separated into filamentous green algae and the remaining diatom fraction. The majority of Se was found in the diatom fraction with only about 1/3rd of total biofilm Se concentration present in the filamentous green algae fraction

Finally, zebrafish (Danio rerio) embryos were exposed to aqueous Se in the form of selenate, selenite, and L-selenomethionine in an attempt to determine if oxidative stress plays a role in selenium embryo toxicity. Selenate and selenite exposure did not induce embryo deformities (lordosis and craniofacial malformation). L-selenomethionine, however, induced significantly higher deformity rates at 100 µg/L compared to controls. Antioxidant rescue of L-selenomethionime induced deformities was attempted in embryos using N-acetylcysteine (NAC). Pretreatment with NAC significantly reduced deformities in the zebrafish embryos secondarily treated with L-selenomethionine, suggesting that oxidative stress may play a role in Se toxicity. Selenite exposure also induced a 6.6-fold increase in glutathione-S-transferase pi class 2 gene expression, which is involved in xenobiotic transformation. No changes in gene expression were observed for selenate or L-selenomethionine-exposed embryos.

The findings in this dissertation contribute to the understanding of how Se bioaccumulates in a lotic system and is transferred through a simulated foodweb in addition to further exploring oxidative stress as a potential mechanism for Se-induced embryo toxicity. Future studies should continue to pursue the role of oxidative stress and other mechanisms in Se toxicity and the biotransformation of Se in aquatic ecosystems.

Olfactory conditioning facilitates diet transition in human infants.

We evaluated whether Pavlovian conditioning methods could be used to increase the ingestion of non-preferred solutions by formula-fed human infants. In baseline measures, 5-7 month old infants sucked less frequently and consumed less water than regular formula. During a 3-day olfactory conditioning period, parents placed a small scented disk, the conditioned stimulus, on the rim of their infants' formula bottle at every feeding. Following this training, infants' responses to water were tested when their water bottles had a disk scented with the training odor, a novel odor, or no odor. Infants tested with the training odor sucked more frequently and consumed significantly more water than they had at baseline. Infants tested with no odor or a novel odor consumed water at or below baseline levels. These data demonstrate that olfactory conditioning can be used to enhance ingestion in infants and suggest that such methods may be useful for infants experiencing difficulty when making transitions from one diet to another.

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.

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.

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.

RUSSIAN THREADS: THE PRESENCE OF RUSSIAN INFLUENCES IN TWENTIETH­ CENTURY ENGLISH CELLO MUSIC

A cursory glance at cello works by English composers during the twentieth- century yields an unexpected relationship to Russian musicians, history, culture, and religion. One must wonder how this connection or "Russian thread" came to be. When considering the working relationship of Benjamin Britten and Mstislav Rostropovich, the likelihood of such a connection is tangible, since their deeply personal friendship influenced Britten's music for cello. However, what is perhaps more interesting is the emergence of connections to Russia in the works of other English composers of the twentieth-century, featuring works from 1913-1996. This project was conceived after close study and analysis of Benjamin Britten's Third Suite for Solo Cello, Op. 87 (1971). Britten's inclusion of Russian folk tunes and an Orthodox Church hymn signaled the penetrating presence of Russian elements in his works. Britten's First Suite for Solo Cello, Op. 72, Third Suite for Cello, Op. 87, and Sonata for Piano and Cello in C, Op. 65 are presented in this project. Further exploration of works for cello by English composers unveiled similar connections to Russia. The Sonata for Cello and Piano of Frank Bridge is likened to Russian romanticism and the Cello Sonata of Sergei Rachmaninoff. William Walton's Cello Concerto was written for the Russian-American cellist Gregor Piatigorsky. Wake Up ...and die is John Tavener's deeply spiritual work, which is rooted in his Russian Orthodoxy. John Ireland, influenced by models of French and Russian Impressionism, contributed works colored with Russian folk influences, of which his Piano Trio No. 2 is an example. Finally, Arnold Bax traveled to Russia as a young man and his Folk Tale and Legend Sonata are imbued with the spirit of Russian folk music and architecture. This dissertation project is comprised of three recitals featuring English works for cello connected by a "Russian Thread." All events took place on the campus of University of Maryland, College Park: Recital #1 on December 4, 2011 in the Gildenhorn Recital Hall of the Clarice Smith Performing Arts Center, Recital #2 on February 11,2012, and Recital #3 on April 15, 2012, both in the Ulrich Recital Hall.