Coordination of platinum therapeutic agents to met-rich motifs of human copper transport protein1.

Platinum therapeutic agents are widely used in the treatment of several forms of cancer. Various mechanisms for the transport of the drugs have been proposed including passive diffusion across the cellular membrane and active transport via proteins. The copper transport protein Ctr1 is responsible for high affinity copper uptake but has also been implicated in the transport of cisplatin into cells. Human hCtr1 contains two methionine-rich Mets motifs on its extracellular N-terminus that are potential platinum-binding sites: the first one encompasses residues 7-14 with amino acid sequence Met-Gly-Met-Ser-Tyr-Met-Asp-Ser and the second one spans residues 39-46 with sequence Met-Met-Met-Met-Pro-Met-Thr-Phe. In these studies, we use liquid chromatography and mass spectrometry to compare the binding interactions between cisplatin, carboplatin and oxaliplatin with synthetic peptides corresponding to hCtr1 Mets motifs. The interactions of cisplatin and carboplatin with Met-rich motifs that contain three or more methionines result in removal of the carrier ligands of both platinum complexes. In contrast, oxaliplatin retains its cyclohexyldiamine ligand upon platinum coordination to the peptide.

Bayesian Gaussian Copula Factor Models for Mixed Data.

Gaussian factor models have proven widely useful for parsimoniously characterizing dependence in multivariate data. There is a rich literature on their extension to mixed categorical and continuous variables, using latent Gaussian variables or through generalized latent trait models acommodating measurements in the exponential family. However, when generalizing to non-Gaussian measured variables the latent variables typically influence both the dependence structure and the form of the marginal distributions, complicating interpretation and introducing artifacts. To address this problem we propose a novel class of Bayesian Gaussian copula factor models which decouple the latent factors from the marginal distributions. A semiparametric specification for the marginals based on the extended rank likelihood yields straightforward implementation and substantial computational gains. We provide new theoretical and empirical justifications for using this likelihood in Bayesian inference. We propose new default priors for the factor loadings and develop efficient parameter-expanded Gibbs sampling for posterior computation. The methods are evaluated through simulations and applied to a dataset in political science. The models in this paper are implemented in the R package bfa.

Facts and Fictions: Feminist Literary Criticism and Cultural Critique, 1968-2012

"Facts and Fictions: Feminist Literary Criticism and Cultural Critique, 1968-2012" is a critical history of the unfolding of feminist literary study in the US academy. It contributes to current scholarly efforts to revisit the 1970s by reconsidering often-repeated narratives about the critical naivety of feminist literary criticism in its initial articulation. As the story now goes, many of the most prominent feminist thinkers of the period engaged in unsophisticated literary analysis by conflating lived social reality with textual representation when they read works of literature as documentary evidence of real life. As a result, the work of these "bad critics," particularly Kate Millett and Andrea Dworkin, has not been fully accounted for in literary critical terms.

This dissertation returns to Dworkin and Millett's work to argue for a different history of feminist literary criticism. Rather than dismiss their work for its conflation of fact and fiction, I pay attention to the complexity at the heart of it, yielding a new perspective on the history and persistence of the struggle to use literary texts for feminist political ends. Dworkin and Millett established the centrality of reality and representation to the feminist canon debates of "the long 1970s," the sex wars of the 1980s, and the more recent feminist turn to memoir. I read these productive periods in feminist literary criticism from 1968 to 2012 through their varied commitment to literary works.

Chapter One begins with Millett, who de-aestheticized male-authored texts to treat patriarchal literature in relation to culture and ideology. Her mode of literary interpretation was so far afield from the established methods of New Criticism that she was not understood as a literary critic. She was repudiated in the feminist literary criticism that followed her and sought sympathetic methods for reading women's writing. In that decade, the subject of Chapter Two, feminist literary critics began to judge texts on the basis of their ability to accurately depict the reality of women's experiences.

Their vision of the relationship between life and fiction shaped arguments about pornography during the sex wars of the 1980s, the subject of Chapter Three. In this context, Dworkin was feminism's "bad critic." I focus on the literary critical elements of Dworkin's theories of pornographic representation and align her with Millett as a miscategorized literary critic. In the decades following the sex wars, many of the key feminist literary critics of the founding generation (including Dworkin, Jane Gallop, Carolyn Heilbrun, and Millett) wrote memoirs that recounted, largely in experiential terms, the history this dissertation examines. Chapter Four considers the story these memoirists told about the rise and fall of feminist literary criticism. I close with an epilogue on the place of literature in a feminist critical enterprise that has shifted toward privileging theory.

Age-related effects on the neural correlates of autobiographical memory retrieval.

Older adults recall less episodically rich autobiographical memories (AM), however, the neural basis of this effect is not clear. Using functional MRI, we examined the effects of age during search and elaboration phases of AM retrieval. Our results suggest that the age-related attenuation in the episodic richness of AMs is associated with difficulty in the strategic retrieval processes underlying recovery of information during elaboration. First, age effects on AM activity were more pronounced during elaboration than search, with older adults showing less sustained recruitment of the hippocampus and ventrolateral prefrontal cortex (VLPFC) for less episodically rich AMs. Second, there was an age-related reduction in the modulation of top-down coupling of the VLPFC on the hippocampus for episodically rich AMs. In sum, the present study shows that changes in the sustained response and coupling of the hippocampus and prefrontal cortex (PFC) underlie age-related reductions in episodic richness of the personal past.

Exploring Musical Diversity in the Collaborative Repertoire from 1880 through 1963

It is essential in musical performance not only to convey the unique language of the composers but also to approach each composition from the perspective of its style. During the 20th century, diverse musical idioms co-existed, sometimes mixing or fusing, yet retaining recognizable characteristics and thereby remaining distinctive. This dissertation explores myriad examples from Late Romanticism/Post- Romanticism, Naturalism, Neo-Classicism, Nationalism and Impressionism composed during this unusually rich period. In order to explore a broad range of collaborative repertoire and to deepen my knowledge of the styles and performance practices relating to these pieces, I studied and performed the repertoire with pianist Eunae Baik–Kim, clarinetist Jihoon Chang, and singers Joshua Brown and Young Joo Lee. The first program featured Post-Romantic, Neo-Classic and Impressionist two-piano works composed by Debussy, Rachmaninoff, and Stravinsky. Each of the three composers used their own distinctive harmonies, rhythms, melodic inventions, pedaling and figurations. In all of the works, both piano parts were densely interwoven, having equal importance. Lied and operatic aria was the focus of the second recital. Brahms’ Vier Ernste Gesänge Op. 121, Ravel’s Don Quichotte a Dulcineé and Italian, French and German operatic arias were the examples of Post-Romanticism and Nationalism. The representative composers were Verdi, Massenet, Korngold, Leoncavallo, Ravel and Wagner. Despite the fact that all of the repertoire was written in traditional musical forms, the composers’ unique voices mark each work as belonging to a particular genre. The third recital focused on Post-Romantic and Impressionistic music written for clarinet and piano: the Première Rhapsodie by Debussy, the Sonata by Poulenc and Brahms’ Sonata in F minor Op. 120, No. 1. These works, although profoundly different in style, share elements of simplicity, clarity and elegance as well as technical virtuosity, articulation and profound musical depth. The three recitals which comprise this dissertation project were performed at the University of Maryland Gildenhorn Recital Hall on February 27, 2010, October 25, 2010, and January 31, 2011. The recitals were recorded on compact disc and are archived within the Digital Repository at the University of Maryland (DRUM).

AUSTRO-GERMAN VIOLIN REPERTORIE FROM BAROQUE THROUGH ROMANTIC PERIOD

At the end of the sixteenth century, Germany had become one of the most active centers of early Baroque music, and therefore Austro-German music came to dominate Western music. An investigation of violin works written during this period reveals the ways in which Austro-German compositions are extraordinary contributions to the violin repertoire. This research warranted further study and performance of these works in order to determine what influence these composers had on the violin repertoire as a whole. For my dissertation recital project, I trace the history of works for violin focusing the violin concerto repertoire in particular. A genre which remained popular throughout the century, the nineteenth-century concerto served primarily as a vehicle for virtuosic display of the violin and piano as never before. For my research I studied and performed works selected from the Baroque through the Romantic period in three recorded recitals with collaborative pianists Ilya Sinaisky, Sun-ha Yun, and Seyon Lee at the Gildenhorn Recital Hall, Clarice Smith Performing Arts Center. I selected particularly prominent pieces which represent the work of significant composers from each period. The composers discussed include Johann Sebastian Bach (1685-1750), owing to the fact that his works are the culmination of the Baroque era during the first half of the eighteenth century; from the Classical period, Wolfgang Amadeus Mozart (1756-1791) all of whom emerged mixing German and Italian traditions into his own style, and Ludwig van Beethoven (1770-1827), the bridge composer between the Classical and the Romantic periods; Romantic composers, Franz Schubert (1979-1828), Johannes Brahms (1833-1897), Robert Schumann (1810-1856), Felix Mendelssohn (1809-1847), and Max Bruch (1838-1920), all who tended to mix Classic and Romantic elements. As a violinist, I learned that their own original sound, rich harmonies and unique expression made these works worthy of becoming masterpieces. I have relished the opportunity for musical and professional growth in exploring these substantial compositions.

The Evolution of Rachmaninov's Pianistic Style from 1892 to 1941 as Seen in Selected Original Works and Transcriptions for Piano

Unlike some other major composer-pianists (Franz Liszt and Alexander Scriabin being the most notable examples), Sergei Rachmaninov did not experience any dramatic changes in his compositional style; one can, however, notice certain stylistic differences between piano works composed during different periods of his long creative life. This dissertation argues that a clear evolution of Rachmaninov's pianistic style through his three creative periods can be traced by examining a selection of his compositions, from his first significant cycle for piano, 5 Marceaux de fantaisie, Op. 3 (1892), all the way through to his last piano work, a transcription of P.I.Tchakovsky's Lullaby, Op. 16, No. 1 (1941). Rachmaninov's life as a composer can be divided into three periods. His early period was ended abruptly by the disastrous premiere ofhis First Symphony in 1897, which caused a deep psychological crisis in the life of the young composer. Piano works of this period are often characterized by relatively simple homophonic texture, when Rachmaninov was clearly influenced by some of his Russian predecessors, most notably Tchaikovsky. His second and most productive period, also known as the period of"Russian maturity," started in 1900, when he began working on the Second Suite for two pianos, Op. 17, and the Second Concerto, Op. 18; this phase ended with the Russian Bolshevik revolution of 1917. Works of this time exhibit a mature style of piano writing, with rich, virtuosic - often considered excessive by many critics - texture and ever-increasing use of chromatic harmonies. Rachmaninov's works of the third period are limited in number owing to the composer's preoccupation with a career as pianist. Original works for piano now give way to revisions of earlier compositions and transcriptions: Rachmaninov's piano writing becomes more efficient and economical without losing any of its virtuosic brilliance. This dissertation project examines in detail, over the course of three piano recitals, a variety of works composed during the "Russian maturity" period, from several Preludes from Op. 23 (1903), the first major cycle for solo piano of the period, to 9 Etudes-Tableaux, Op.39 (1917), the last one; the early period is represented by 3 of 5 Marceaux defantaisie, Op. 3 (1892), while the late period is shown through several piano transcriptions and revised versions of the remaining 2 pieces from Op. 3.

BioHackathon series in 2011 and 2012: penetration of ontology and linked data in life science domains.

The application of semantic technologies to the integration of biological data and the interoperability of bioinformatics analysis and visualization tools has been the common theme of a series of annual BioHackathons hosted in Japan for the past five years. Here we provide a review of the activities and outcomes from the BioHackathons held in 2011 in Kyoto and 2012 in Toyama. In order to efficiently implement semantic technologies in the life sciences, participants formed various sub-groups and worked on the following topics: Resource Description Framework (RDF) models for specific domains, text mining of the literature, ontology development, essential metadata for biological databases, platforms to enable efficient Semantic Web technology development and interoperability, and the development of applications for Semantic Web data. In this review, we briefly introduce the themes covered by these sub-groups. The observations made, conclusions drawn, and software development projects that emerged from these activities are discussed.

AMERICAN WOMEN COMPOSERS: SELECTED PUBLISHED WORKS FOR FLUTE AND PIANO AND FOR UNACCOMPANIED FLUTE COMPOSED BETWEEN 1930 AND 2008

The music of women composers often comprises only a small percentage of flutists‘ repertoire, yet there are actually many active women composers, many of whom have written for the flute. The aim of this dissertation is to chronicle a selection of works by several American women composers that have contributed to accessible flute repertoire. For the purpose of this dissertation, accessibility is described by the following parameters: works that limit the use of extended techniques, works that are suitable for performers from high school through a reasonably advanced level, works that are likely to elicit emotionally musical communication from the performer to the listener, and works that are reasonably available through music stores or outlets on the Internet that have a fairly comprehensive reach to the general public. My subjective judgment also played a role in the final selection of the 25 works included as part of this dissertation, and performed on three musically well-balanced recitals. A variety of resources were consulted for the repertoire, including Boenke‘s Flute Music by Women Composers: An Annotated Catalog, and the catalogs of publishers such as Arsis Press and Hildegard Publishing, both of which specialize in the music of women composers. The works performed and discussed are the following: Adrienne Albert – Sunswept; Marion Bauer – Prelude and Fugue, Op. 43.; Marilyn Bliss – Lament; Ann Callaway – Updraft; Ruth Crawford – Diaphonic Suite; Emma Lou Diemer – Sonata; Vivian Fine – Emily’s Images; Cynthia Folio – Arca Sacra; Nancy Galbraith – Atacama; Lita Grier – Sonata; Jennifer Higdon – The Jeffrey Mode; Edie Hill – This Floating World; Katherine Hoover – Masks; Mary Howe – Interlude between Two Pieces; Laura Kaminsky – Duo; Libby Larsen – Aubade; Alex Shapiro – Shiny Kiss; Judith Shatin – Coursing Through the Still Green; Faye-Ellen Silverman – Taming the Furies; Augusta Read Thomas – Euterpe’s Caprice; Joan Tower – Valentine Trills; Ludmila Ulehla – Capriccio; Elizabeth Vercoe – Kleemation; Gwyneth Walker – Sonata; and Judith Lang Zaimont – ‘Bubble-Up’ Rag. All of these works are worthy alternatives to the more frequently played flute repertoire, and they serve as a good starting point for anyone interested i n exploring the works of women composers.

The Dietary Approaches to Stop Hypertension (DASH) eating pattern in special populations.

The Dietary Approaches to Stop Hypertension (DASH) trial showed that a diet rich in fruits, vegetables, low-fat dairy products with reduced total and saturated fat, cholesterol, and sugar-sweetened products effectively lowers blood pressure in individuals with prehypertension and stage I hypertension. Limited evidence is available on the safety and efficacy of the DASH eating pattern in special patient populations that were excluded from the trial. Caution should be exercised before initiating the DASH diet in patients with chronic kidney disease, chronic liver disease, and those who are prescribed renin-angiotensin-aldosterone system antagonist, but these conditions are not strict contraindications to DASH. Modifications to the DASH diet may be necessary to facilitate its use in patients with chronic heart failure, uncontrolled diabetes mellitus type II, lactose intolerance, and celiac disease. In general, the DASH diet can be adopted by most patient populations and initiated simultaneously with medication therapy and other lifestyle interventions.

Be rich or don’t be sick: Estimating Vietnamese patients’ risk of falling into destitution

This paper represents the first research attempt to estimate the probabilities for Vietnamese patients to fall into destitution facing financial burdens occurring during their curative stay in hospital. The study models the risk against such factors as level of insurance coverage, location of patient, costliness of treatment, among others. The results show that very high probabilities of destitution, approximately 70%, apply to a large group of patients, who are nonresident, poor and ineligible for significant insurance coverage. There is also a probability of 58% that low-income patients who are seriously ill and face higher health care costs would quit their treatment. These facts will put Vietnamese government’s ambitious plan of increasing both universal coverage (UC) to 100% of expenditure and rate of UC beneficiaries to 100% at a serious test. The study also raises issues of asymmetric information and alternative financing options for the poor, who are most exposed to risk of destitution, following market-based health care reforms.

Berufsschulumfrage 2012. Einflussfaktoren auf die Berufswahl und Verbleibentscheidung von Auszubildenden im Landkreis Mecklenburgische Seenplatte

Berufswahlsentscheidung und die Frage nach dem Gehen oder Bleiben ist nicht nur für viele junge Menschen in ländlichen Regionen eine wichtige Frage, sondern auch für die im Übergang Schule-Beruf arbeitenden Menschen und Akteure der jeweiligen Kommune. Vor dem Hintergrund der Abwanderungstendenzen und der Optimierung der Übergänge Schule-Beruf hat die Stabsstelle Bildung des Landkreises Mecklenburgische Seenplatte repräsentativ 2800 Auszubildende des Landkreises befragt über die Einflussfaktoren für ihre Berufswahl und über ihre Entscheidung hier zu bleiben oder gehen befragt. Die z.T. überraschenden Ergebnisse werden in dieser Studie zusammen mit Handlungsempfehlungen dargestellt. (DIPF/Autor)

Age and gender influences on sensory perceptions of novel low cost nutrient-rich food products developed using traditional Ghanaian food ingredients

Background: A number of factors are known to influence food preferences and acceptability of new products. These include their sensory characteristics and strong, innate neural influences. In designing foods for any target group, it is important to consider intrinsic and extrinsic characteristics which may contribute to palatability, and acceptability of foods. Objective: To assess age and gender influences on sensory perceptions of novel low cost nutrient-rich food products developed using traditional Ghanaian food ingredients. Materials and Methods: In this study, a range of food products were developed from Ghanaian traditional food sources using the Food Multimix (FMM) concept. These products were subjected to sensory evaluation to assess the role of sensory perception on their acceptability among different target age groups across the life cycle (aged 11-68 years olds) and to ascertain any possible influences of gender on preference and choice. Variables including taste, odour, texture, flavour and appearance were tested and the results captured on a Likert scale and scores of likeness and acceptability analysed. Multivariate analyses were used to develop prediction models for targeted recipe development for different target groups. Multiple factor analysis of variance (ANOVA) and logistic linear regression were employed to test the strength of acceptability and to ascertain age and gender influences on product preference. Results: The results showed a positive trend in acceptability (r = 0.602) which tended towards statistical significance (p = 0.065) with very high product favourability rating (91% acceptability; P=0.005). However, age [odds ratios=1.44 (11-15 years old) odds ratios=2.01 (18-68 years old) and gender (P=0.000)] were major influences on product preference with children and females (irrespective of age) showing clear preferences or dislike of products containing certain particular ingredients. Conclusion: These findings are potentially useful in planning recipes for feeding interventions involving different vulnerable and target groups.

Changes in the properties of Bacillus thuringiensis after prolonged culture in a rich medium

AIM: To investigate the effect of repeated culture in a rich medium on certain genetic, metabolic, pathogenic and structural characteristics of fresh isolates of Bacillus thuringiensis. METHODS AND RESULTS: Four strains of B. thuringiensis, which had been isolated in vegetative form from leaf surfaces, were grown for 500 generations in batch culture in a rich medium. One of the strains, S4g, differed from the parent in the following respects: greater cell width; changed plasmid profile; complete loss of ability to produce delta-endotoxins; loss of ability to produce beta-exotoxin and disruption of vip3 gene; radically different fatty acid composition; and altered metabolic activity. Two of the other evolved strains (S1g and S6g) showed differences in fatty acid profiles compared with the parents. Genetic finger-printing showed that there were also mutations in the cry genes of two of the evolved strains (S1g and S2g). The delta-endotoxins of strain S6g were significantly less toxic to the larvae of Pieris brassica compared with those of the parent and it also differed in the plasmid content. CONCLUSION: Radical and unpredictable changes can occur in fresh isolates of B. thuringiensis when subjected to growth in the laboratory. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first analysis of a Gram positive and biotechnologically significant bacterium after repeated laboratory culture. It is of great relevance to the biotechnological exploitation of B. thuringiensis that prolonged growth of environmental isolates on laboratory culture media can have profound effects on their structure, genome and virulence determinants.