Bioengineered human myobundles mimic clinical responses of skeletal muscle to drugs.

Existing in vitro models of human skeletal muscle cannot recapitulate the organization and function of native muscle, limiting their use in physiological and pharmacological studies. Here, we demonstrate engineering of electrically and chemically responsive, contractile human muscle tissues ('myobundles') using primary myogenic cells. These biomimetic constructs exhibit aligned architecture, multinucleated and striated myofibers, and a Pax7(+) cell pool. They contract spontaneously and respond to electrical stimuli with twitch and tetanic contractions. Positive correlation between contractile force and GCaMP6-reported calcium responses enables non-invasive tracking of myobundle function and drug response. During culture, myobundles maintain functional acetylcholine receptors and structurally and functionally mature, evidenced by increased myofiber diameter and improved calcium handling and contractile strength. In response to diversely acting drugs, myobundles undergo dose-dependent hypertrophy or toxic myopathy similar to clinical outcomes. Human myobundles provide an enabling platform for predictive drug and toxicology screening and development of novel therapeutics for muscle-related disorders.

Nrg1 is an injury-induced cardiomyocyte mitogen for the endogenous heart regeneration program in zebrafish.

Heart regeneration is limited in adult mammals but occurs naturally in adult zebrafish through the activation of cardiomyocyte division. Several components of the cardiac injury microenvironment have been identified, yet no factor on its own is known to stimulate overt myocardial hyperplasia in a mature, uninjured animal. In this study, we find evidence that Neuregulin1 (Nrg1), previously shown to have mitogenic effects on mammalian cardiomyocytes, is sharply induced in perivascular cells after injury to the adult zebrafish heart. Inhibition of Erbb2, an Nrg1 co-receptor, disrupts cardiomyocyte proliferation in response to injury, whereas myocardial Nrg1 overexpression enhances this proliferation. In uninjured zebrafish, the reactivation of Nrg1 expression induces cardiomyocyte dedifferentiation, overt muscle hyperplasia, epicardial activation, increased vascularization, and causes cardiomegaly through persistent addition of wall myocardium. Our findings identify Nrg1 as a potent, induced mitogen for the endogenous adult heart regeneration program.

THE PIANO MUSIC OF ROBERT SCHUMANN (1810-1856) AND JOHANNES BRAHMS (1833- 1897): A SURVEY OF CONCERTI, VARIATIONS, AND CHARACTER PIECES

Robert Schumann (1810-1856) and Johannes Brahms (1833-1897), in some ways Robert Schumann's artistic descendant, are the most important and representative German piano composers during the Romantic period. Schumann was already a mature and established musician in 1853 when he first met the young Brahms and recognized his talents, an encounter that had a long-lasting affect on the lives and careers of both men. After Schumann’s mental breakdown and death, Brahms maintained his admiration of Schumann’s music and preserved an intimate relationship with Clara Schumann. In spite of the personal and musical closeness of the two men, Schumann’s music is stylistically distinct from that of Brahms. Brahms followed traditions from Baroque and Classical music, and avoided using images and expressive titles in his music. Brahms extraordinarily intermingled earlier musical forms with multicolored tones of German Romanticism. In contrast, Schumann saw himself as a radical composer devoted to personal emotionalism and spontaneity. He favored programmatic titles for his character pieces and extra-musical references in his music. While developing their own musical styles as German Romantic composers, Schumann and Brahms both utilized the piano as a resourceful tool for self-realization and compositional development. To investigate and compare the main characteristics of Schumann and Brahms’s piano music, I looked at three genres. First, in the category of the piano concerto, I chose two major Romantic works, Schumann’s A minor concerto and Brahms’s B-flat major concerto. Second, for the category of piano variations I included two sets by Brahms because the variation framework was such an important vehicle for him to express his musical thoughts. Schumann’s unique motivic approach to variation is displayed vividly in his character-piece cycle Carnaval. Third, the category of the character piece, perhaps the favorite medium of Romantic expression at the piano, is shown by Schumann’s Papillons and Brahms’s sets of pieces Op.118 and Op.119. This performance dissertation consists of three recitals performed in the Gildenhorn Recital Hall at the University of Maryland, College Park. These recitals are documented on compact disc recordings that are housed within the University of Maryland Library System.

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.

SCHUBERT’S WINTERREISE AND THE PIANO TRIO IN Eb; TWO REMARKABLE WORKS FROM ONE REMARKABLE YEAR – 1827: A RECORDING PROJECT

During Franz Schubert’s penultimate year of 1827, he produced two profoundly important and mature works that are the focus of this recording project. The works are, in chronological order: • Winterreise (cycle of 24 songs on the poetry of Wilhelm Müller, 1794-1827) • Piano Trio in Eb Major, Op. 100, D. 929 A unique feature of the project is to present Winterreise in two poetic orders: as traditionally performed and published by Schubert, and in the final ordering published by the poet. The program notes accompanying the dissertation’s three compact discs have extensive information as well as comparative tables of Müller’s and Schubert’s final ordering of the cycle. There are significant differences in ordering, and ultimately the listener will determine which is more dramatically satisfying. Dark melancholy is the central emotion in Winterreise, which Schubert composed at various times throughout 1827 in a mood of corresponding gloom and distress. By contrast, the summer and fall of that year produced, in quick succession, the two glowing and remarkable Piano Trios in Bb and Eb, the second of which is included on these compact discs. The contrast between the trios and Winterreise follows the outward circumstances of Schubert’s life and health, a pattern of sorrow and later consolation and elation. The sound recordings for this dissertation recording project are available on three compact discs that can be found in the Digital Repository at the University of Maryland (DRUM). Winterreise was recorded in August 2009, at the University of Baltimore recital hall in Baltimore, Maryland with University of Maryland Professor François Loup. The trio, recorded in live performance in Baltimore in the spring of 2010, features two members of the Baltimore Symphony Orchestra: Qing Li, B.S.O. principal second violin, and Bo Li, B.S.O. section cellist.

Preliminary experience of ovarian tissue cryopreservation procedure: alternatives, perspectives and feasibility

Chemotherapy and radiotherapy induce premature ovarian failure in many patients treated for oncological or benign diseases. The present paper reviews the risk of developing premature ovarian failure according to the type of treatment and the different options to preserve fertility, focusing on the cryopreservation of ovarian tissue. This technique constitutes a promising approach to preserve the fertility of young patients and offers the advantage of storing a large number of follicles that could be subsequently transplanted or cultured in vitro to obtain mature oocytes. Based on 34 requests, from which 19 were performed, the feasibility of the ovarian cryopreservation procedure is evaluated. The medical and ethical approaches of this protocol are also discussed. Cryopreservation of ovarian tissue constitutes new hope for many patients, but must still be kept for selected cases, with a significant risk of premature ovarian failure after treatments such as bone marrow transplantation.

Bordetella pertussis infection in 2-month-old infants promotes type 1 T cell responses.

Neonatal immaturity of the immune system is currently believed to generally limit the induction of immune responses to vaccine Ags and to skew them toward type 2 responses. We demonstrated here that Bordetella pertussis infection in very young infants (median, 2 mo old) as well as the first administration of whole-cell pertussis vaccine induces B. pertussis Ag-specific IFN-gamma secretion by the PBMC of these infants. IFN-gamma was secreted by both CD4(+) and CD8(+) T lymphocytes, and the levels of Ag-induced IFN-gamma secretion did not correlate with the age of the infants. Appearance of the specific Th-1 cell-mediated immunity was accompanied by a general shift of the cytokine secretion profile of these infants toward a stronger Th1 profile, as evidenced by the response to a polyclonal stimulation. We conclude that the immune system of 2-mo-old infants is developmentally mature enough to develop Th1 responses in vivo upon infection by B. pertussis or vaccination with whole-cell pertussis vaccines.

Hydrocarbon field size distributions: a case study in mixed integer nonlinear programming

Of key importance to oil and gas companies is the size distribution of fields in the areas that they are drilling. Recent arguments suggest that there are many more fields yet to be discovered in mature provinces than had previously been thought because the underlying distribution is monotonic not peaked. According to this view the peaked nature of the distribution for discovered fields reflects not the underlying distribution but the effect of economic truncation. This paper contributes to the discussion by analysing up-to-date exploration and discovery data for two mature provinces using the discovery-process model, based on sampling without replacement and implicitly including economic truncation effects. The maximum likelihood estimation involved generates a high-dimensional mixed-integer nonlinear optimization problem. A highly efficient solution strategy is tested, exploiting the separable structure and handling the integer constraints by treating the problem as a masked allocation problem in dynamic programming.

Metaphors and metamorphoses: narratives of identity during times of crisis

The narrative of transformative crisis appears in both autobiographical and fictional accounts of individual lives; it typically involves a difficult or traumatic episode and a period of self-questioning out of which a person emerges more able and more emotionally mature than before (Booker, 2005; Erikson, 1968; Tedeschi and Calhoun, 1995). The present study used interviews to elicit 22 narratives about crises experienced between the ages of 25 and 40, and about any developmental transformation and change that surrounded these crises. Analysis revealed a common four-phase process to the crisis episodes, common metaphors and recurrent descriptions of identity metamorphosis, ie. of ‘becoming a new person’. Comparison of these findings with theory on fictional plots shows a clear parallel between the four-phase process of crisis found in the current study and the ‘rebirth’ plot described by Booker (2005). The theoretical significance of these findings and interpretations is discussed.

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Draws attention to the difficulties of the requirement that pupillages must usually be undertaken full time, particularly for mature and female entrants to the profession. Suggests options for making pupillage more flexible and therefore widening access to the Bar. [From Legal Journals Index]

Review paper: role of aluminum in glass-ionomer dental cements and its biological effects

The role of aluminum in glass-ionomers and resin-modified glass-ionomers for dentistry is reviewed. Aluminum is included in the glass component of these materials in the form of Al(2)O(3) to confer basicity on the glass and enable the glass to take part in the acid-base setting reactions. Results of studies of these reactions by FTIR and magic-angle spinning (MAS)-NMR spectroscopy are reported and the role of aluminum is discussed in detail. Aluminum has been shown to be present in the glasses in predominantly 4-coordination, as well as 5- and 6-coordination, and during setting a proportion of this is converted to 6-coordinate species within the matrix of the cement. Despite this, mature cements may contain detectable amounts of both 4- and 5-coordinate aluminum. Aluminum has been found to be leached from glass-ionomer cements, with greater amounts being released under acidic conditions. It may be associated with fluoride, with which it is known to complex strongly. Aluminum that enters the body via the gastro-intestinal tract is mainly excreted, and only about 1% ingested aluminum crosses the gut wall. Calculation shows that, if a glass-ionomer filling dissolved completely over 5 years, it would add only an extra 0.5% of the recommended maximum intake of aluminum to an adult patient. This leads to the conclusion that the release of aluminum from either type of glass-ionomer cement in the mouth poses a negligible health hazard.

Kinetic studies of the effect of varnish on water loss by glass-ionomer cements

OBJECTIVES: This paper reports a study of the water loss behaviour of two commercial glass-ionomer cements coated with varnishes. METHODS: For each cement (Fuji IX Fast or Chemflex), specimens (6mmdiameterx2mm depth) were prepared and cured for 10min at 37 degrees C. They were exposed to a desiccating environment over H(2)SO(4) either uncoated or coated with the appropriate varnish (Fuji Varnish, a solvent-based lacquer, or Fuji Coat, a light-cured varnish). Four specimens were prepared for each material. They were weighed at hourly intervals for 6h, daily for up to 5 days, then weekly thereafter until equilibration. RESULTS: Unlike the uncoated specimens, water loss from varnished cements was not Fickian, but followed the form: mass loss=A/t+B, where t is time, A and B are constants specific to each cement/varnish combination. A varied from 1.22 to 1.30 (mean 1.26, standard deviation 0.04), whereas B varied from 1.54 to 2.09 (mean -1.83, standard deviation 0.29). At equilibrium, varnished specimens lost much less water than unvarnished ones (p>0.01) but there was no significant difference between the solvent-based and the light-cured varnishes. SIGNIFICANCE: Varnishes protect immature glass-ionomer cements from drying out by altering the mechanism of water loss. This slows the rate of drying but does not necessarily change the total amount of water retained. It confirms that, in clinical use, glass-ionomer restoratives should be varnished to allow them to mature satisfactorily.

Bridging the gap with teamwork: collaborative leadership for communities of practice in the learning and skills sector

Collaborative approaches in leadership and management are increasingly acknowledged to play a key role in successful institutions in the learning and skills sector (LSS) (Ofsted, 2004). Such approaches may be important in bridging the potential 'distance' (psychological, cultural, interactional and geographical) (Collinson, 2005) that may exist between 'leaders' and 'followers', fostering more democratic communal solidarity. This paper reports on a 2006-07 research project funded by the Centre for Excellence in Leadership (CEL) that aimed to collect and analyse data on 'collaborative leadership' (CL) in the learning and skills sector. The project investigated collaborative leadership and its potential for benefiting staff through trust and knowledge-sharing in communities of practice (CoPs). The project forms part of longer-term educational research investigating leadership in a collaborative inquiry process (Jameson et al., 2006). The research examined the potential for CL to benefit institutions, analysing respondents' understanding of and resistance to collaborative practices. Quantitative and qualitative data from senior managers and lecturers was analysed using electronic data in SPSS and Tropes Zoom. The project aimed to recommend systems and practices for more inclusive, diverse leadership (Lumby et al., 2005). Collaborative leadership has increasingly gained international prominence as emphasis shifted towards team leadership beyond zero-sum 'leadership'/ 'followership' polarities into more mature conceptions of shared leadership spaces, within which synergistic leadership spaces can be mediated. The relevance of collaboration within the LSS has been highlighted following a spate of recent government-driven policy developments in FE. The promotion of CL addresses concerns about the apparent 'remoteness' of some senior managers, and the 'neo-management' control of professionals which can increase 'distance' between leaders and 'followers' and may de-professionalise staff in an already disempowered sector. Positive benefit from 'collaborative advantage' tends to be assumed in idealistic interpretations of CL, but potential 'collaborative inertia' may be problematic in a sector characterised by rapid top-down policy changes and continuous external audit and surveillance. Constant pressure for achievement against goals leaves little time for democratic group negotiations, despite the desires of leaders to create a more collaborative ethos. Yet prior models of intentional communities of practice potentially offer promise for CL practice to improve group performance despite multiple constraints. The CAMEL CoP model (JISC infoNet, 2006) was linked to the project, providing one practical way of implementing CL within situated professional networks.The project found that a good understanding of CL was demonstrated by most respondents, who thought it could enable staff to share power and work in partnership to build trust and conjoin skills, abilities and experience to achieve common goals for the good of the sector. However, although most respondents expressed agreement with the concept and ideals of CL, many thought this was currently an idealistically democratic, unachievable pipe dream in the LSS. Many respondents expressed concerns with the 'audit culture' and authoritarian management structures in FE. While there was a strong desire to see greater levels of implementation of CL, and 'collaborative advantage' from the 'knowledge sharing benefit potential' of team leadership, respondents also strongly advised against the pitfalls of 'collaborative inertia'. A 'distance' between senior leadership views and those of staff lower down the hierarchy regarding aspects of leadership performance in the sector was reported. Finally, the project found that more research is needed to investigate CL and develop innovative methods of practical implementation within autonomous communities of professional practice.

Biological impacts of enhanced alkalinity in Carcinus maenas

Further steps are needed to establish feasible alleviation strategies that are able to reduce the impacts of ocean acidification, whilst ensuring minimal biological side-effects in the process. Whilst there is a growing body of literature on the biological impacts of many other carbon dioxide reduction techniques, seemingly little is known about enhanced alkalinity. For this reason, we investigated the potential physiological impacts of using chemical sequestration as an alleviation strategy. In a controlled experiment, Carcinus maenas were acutely exposed to concentrations of Ca(OH)2 that would be required to reverse the decline in ocean surface pH and return it to pre-industrial levels. Acute exposure significantly affected all individuals' acid-base balance resulting in slight respiratory alkalosis and hyperkalemia, which was strongest in mature females. Although the trigger for both of these responses is currently unclear, this study has shown that alkalinity addition does alter acid-base balance in this comparatively robust crustacean species.

Strong preference for decapod prey by the western rock lobster Panulirus cygnus

Western rock lobsters, Panulirus cygnus are an abundant benthic consumer distributed along the temperate west coast of Australia and constitute the largest single species fishery in Australia. As a dominant consumer, it is important to understand their predator-prey interactions as they can potentially exert strong trophic effects, and may influence ecosystem function as seen in other spiny lobster species. While previous field studies have focused on the diet composition of P. cygnus, this study investigated their preference for various benthic invertebrate prey to better understand the likely predator-prey interactions of P. cygnus. Prey preferences of small sub-legal juvenile lobsters, as well as medium and large legal-sized mature lobsters were investigated using laboratory feeding trials to identify size-associated differences in lobster prey preference. Handling time and diet quality were investigated to estimate energetic cost and gain from consuming different prey which may explain prey choice by lobsters. It was found that large lobsters preferred crabs and mussels while medium and small lobsters preferred crabs over mussels, gastropods, and sea urchins. This suggests that strong predator-prey interactions between P. cygnus and crabs may occur in the wild.