Christian Gottlob Neefe and the Bonn National Theatre, with New Light on the Beethoven Family

When the Bonn stage was closed after the death of Elector Max Friedrich in 1784, the director of its theatre company, Gustav Friedrich Wilhelm Großmann, decided to leave the city to further his career elsewhere in the Rhinelands. During the next few years, he was kept informed about developments in Bonn by two of his erstwhile colleagues, Christian Gottlob Neefe and Nikolaus Simrock, whose correspondence paints a vivid picture of musical life in the city during the later 1780s. The new Elector, Maximilian Franz, permitted a visiting troupe to perform during Carnival each year, but repeatedly delayed the decision to re-establish a resident troupe. In 1787 Christoph Brandt, a singer in the Bonn Hofkapelle, attempted a home-grown initiative, perhaps to test the market for a new permanent company. Although this failed almost immediately, a single, well-attended public rehearsal of Monsigny’s Le Déserteur was given, in which Johann van Beethoven made what was probably his last stage appearance. In a letter dated 14 May 1787, Simrock rated his performance ‘zimlich gut’. In the event, a new Bonn troupe was not recruited until 1789, when it featured the young singer Magdalena Willmann. Neefe and his musical colleagues were relieved finally to be able to resume their theatrical careers.

Virtual Microscopy and Digital Pathology in Training and Education

Traditionally, education and training in pathology has been delivered using textbooks, glass slides and conventional microscopy. Over the last two decades, the number of web-based pathology resources has expanded dramatically with centralized pathological resources being delivered to many students simultaneously. Recently, whole slide imaging technology allows glass slides to be scanned and viewed on a computer screen via dedicated software. This technology is referred to as virtual microscopy and has created enormous opportunities in pathological training and education. Students are able to learn key histopathological skills, e.g. to identify areas of diagnostic relevance from an entire slide, via a web-based computer environment. Students no longer need to be in the same room as the slides. New human–computer interfaces are also being developed using more natural touch technology to enhance the manipulation of digitized slides. Several major initiatives are also underway introducing online competency and diagnostic decision analysis using virtual microscopy and have important future roles in accreditation and recertification. Finally, researchers are investigating how pathological decision-making is achieved using virtual microscopy and modern eyetracking devices. Virtual microscopy and digital pathology will continue to improve how pathology training and education is delivered.

Nineteenth and twentieth century sea-level changes in Tasmania and New Zealand

Positive deviations from linear sea-level trends represent important climate signals if they are persistent and geographically widespread. This paper documents rapid sea-level rise reconstructed from sedimentary records obtained from salt marshes in the Southwest Pacific region (Tasmania and New Zealand). A new late Holocene relative sea-level record from eastern Tasmania was dated by AMS(14)C (conventional, high precision and bomb-spike), Cs-137, Pb-210, stable Pb isotopic ratios, trace metals, pollen and charcoal analyses. Palaeosea-level positions were determined by foraminiferal analyses. Relative sea level in Tasmania was within half a metre of present sea level for much of the last 6000 yr. Between 1900 and 1950 relative sea level rose at an average rate of 4.2 +/- 0.1 mm/yr. During the latter half of the 20th century the reconstructed rate of relative sea-level rise was 0.7 +/- 0.6 mm/yr. Our study is consistent with a similar pattern of relative sea-level change recently reconstructed for southern New Zealand. The change in the rate of sea-level rise in the SW Pacific during the early 20th century was larger than in the North Atlantic and could suggest that northern hemisphere land-based ice was the most significant melt source for global sea-level rise. (C) 2011 Elsevier B.V. All rights reserved.

Development of liposome gel based formulations for intravaginal delivery of the recombinant HIV-1 envelope protein CN54gp140

Mucosally-administered vaccine strategies are widely investigated as a promising means of preventing HIV infection. This study describes the development of liposomal gel formulations, and novel lyophilised variants, comprising HIV-1 envelope glycoprotein, CN54gp140, encapsulated within neutral, positively charged or negatively charged liposomes. The CN54gp140 liposomes were evaluated for mean vesicle diameter, polydispersity, morphology, zeta potential and antigen encapsulation efficiency before being incorporated into hydroxyethyl cellulose (HEC) aqueous gel and subsequently lyophilised to produce a rod-shaped solid dosage form for practical vaginal application. The lyophilised liposome-HEC rods were evaluated for moisture content and redispersibility in simulated vaginal fluid. Since these rods are designed to revert to gel form following intravaginal application, mucoadhesive, mechanical (compressibility and hardness) and rheological properties of the reformed gels were evaluated. The liposomes exhibited good encapsulation efficiency and the gels demonstrated suitable mucoadhesive strength. The freeze-dried liposome-HEC formulations represent a novel formulation strategy that could offer potential as stable and practical dosage form.

Proteolytic cleavage of elafin by 20S proteasome may contribute to inflammation in acute lung injury

RATIONALE:
We hypothesise that elafin levels in acute lung injury (ALI) decrease over time due, in part, to proteolytic degradation as observed in other lung diseases.
OBJECTIVES:
The aim of this study was to characterise temporal changes in elafin concentration in patients with ALI and to evaluate whether a decrease in elafin levels is due to elevated protease activity.
METHODS:
Bronchoalveolar lavage fluid (BALF) was obtained from patients with ALI within 48 h of onset of ALI (day 0), at day 3 and at day 7. Elafin levels were quantified by ELISA. Elafin susceptibility to proteolytic cleavage by ALI BALF was assessed by Western blot and by high-performance liquid chromatography-mass spectrometry.
MEASUREMENTS AND MAIN RESULTS:
Elafin levels were found to be significantly increased at the onset of ALI compared with healthy volunteers and fell significantly by day 7 compared with day 0. In contrast, levels of secretory leukocyte protease inhibitor did not decrease over time. This decrease in elafin was due to cleavage by the 20S proteasome which was significantly increased in ALI BALF. Incubation of ALI BALF with the proteasome inhibitor epoxomicin confirmed that 20S proteasome protease activity was responsible for proteolytic cleavage of elafin, resulting in diminished anti-elastase activity. In addition, free neutrophil elastase activity significantly increased in ALI BALF from day 0 to day 7.
CONCLUSIONS:
Elafin concentrations fall within the pulmonary compartment over the course of ALI as a result of proteolytic degradation. This loss of elafin may predispose people, in part, to excessive inflammation in ALI.