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.

Exhausted CD8 T cells downregulate the IL-18 receptor and become unresponsive to inflammatory cytokines and bacterial co-infections.

During many chronic infections virus-specific CD8 T cells succumb to exhaustion as they lose their ability to respond to antigenic activation. Combinations of IL-12, IL-18, and IL-21 have been shown to induce the antigen-independent production of interferon (IFN)-γ by effector and memory CD8 T cells. In this study we investigated whether exhausted CD8 T cells are sensitive to activation by these cytokines. We show that effector and memory, but not exhausted, CD8 T cells produce IFN-γ and upregulate CD25 following exposure to certain combinations of IL-12, IL-18, and IL-21. The unresponsiveness of exhausted CD8 T cells is associated with downregulation of the IL-18-receptor-α (IL-18Rα). Although IL-18Rα expression is connected with the ability of memory CD8 T cells to self-renew and efflux rhodamine 123, the IL-18Rα(lo) exhausted cells remained capable of secreting this dye. To further evaluate the consequences of IL-18Rα downregulation, we tracked the fate of IL-18Rα-deficient CD8 T cells in chronically infected mixed bone marrow chimeras and discovered that IL-18Rα affects the initial but not later phases of the response. The antigen-independent responsiveness of exhausted CD8 T cells was also investigated following co-infection with Listeria monocytogenes, which induces the expression of IL-12 and IL-18. Although IL-18Rα(hi) memory cells upregulated CD25 and produced IFN-γ, the IL-18Rα(lo) exhausted cells failed to respond. Collectively, these findings indicate that as exhausted T cells adjust to the chronically infected environment, they lose their susceptibility to antigen-independent activation by cytokines, which compromises their ability to detect bacterial co-infections.

Core and Shell Song Systems Unique to the Parrot Brain.

The ability to imitate complex sounds is rare, and among birds has been found only in parrots, songbirds, and hummingbirds. Parrots exhibit the most advanced vocal mimicry among non-human animals. A few studies have noted differences in connectivity, brain position and shape in the vocal learning systems of parrots relative to songbirds and hummingbirds. However, only one parrot species, the budgerigar, has been examined and no differences in the presence of song system structures were found with other avian vocal learners. Motivated by questions of whether there are important differences in the vocal systems of parrots relative to other vocal learners, we used specialized constitutive gene expression, singing-driven gene expression, and neural connectivity tracing experiments to further characterize the song system of budgerigars and/or other parrots. We found that the parrot brain uniquely contains a song system within a song system. The parrot "core" song system is similar to the song systems of songbirds and hummingbirds, whereas the "shell" song system is unique to parrots. The core with only rudimentary shell regions were found in the New Zealand kea, representing one of the only living species at a basal divergence with all other parrots, implying that parrots evolved vocal learning systems at least 29 million years ago. Relative size differences in the core and shell regions occur among species, which we suggest could be related to species differences in vocal and cognitive abilities.

Leptin metabolically licenses T cells for activation to link nutrition and immunity.

Immune responses are highly energy-dependent processes. Activated T cells increase glucose uptake and aerobic glycolysis to survive and function. Malnutrition and starvation limit nutrients and are associated with immune deficiency and increased susceptibility to infection. Although it is clear that immunity is suppressed in times of nutrient stress, mechanisms that link systemic nutrition to T cell function are poorly understood. We show in this study that fasting leads to persistent defects in T cell activation and metabolism, as T cells from fasted animals had low glucose uptake and decreased ability to produce inflammatory cytokines, even when stimulated in nutrient-rich media. To explore the mechanism of this long-lasting T cell metabolic defect, we examined leptin, an adipokine reduced in fasting that regulates systemic metabolism and promotes effector T cell function. We show that leptin is essential for activated T cells to upregulate glucose uptake and metabolism. This effect was cell intrinsic and specific to activated effector T cells, as naive T cells and regulatory T cells did not require leptin for metabolic regulation. Importantly, either leptin addition to cultured T cells from fasted animals or leptin injections to fasting animals was sufficient to rescue both T cell metabolic and functional defects. Leptin-mediated metabolic regulation was critical, as transgenic expression of the glucose transporter Glut1 rescued cytokine production of T cells from fasted mice. Together, these data demonstrate that induction of T cell metabolism upon activation is dependent on systemic nutritional status, and leptin links adipocytes to metabolically license activated T cells in states of nutritional sufficiency.

Postnatally-transmitted HIV-1 Envelope variants have similar neutralization-sensitivity and function to that of nontransmitted breast milk variants.

BACKGROUND: Breastfeeding is a leading cause of infant HIV-1 infection in the developing world, yet only a minority of infants exposed to HIV-1 via breastfeeding become infected. As a genetic bottleneck severely restricts the number of postnatally-transmitted variants, genetic or phenotypic properties of the virus Envelope (Env) could be important for the establishment of infant infection. We examined the efficiency of virologic functions required for initiation of infection in the gastrointestinal tract and the neutralization sensitivity of HIV-1 Env variants isolated from milk of three postnatally-transmitting mothers (n = 13 viruses), five clinically-matched nontransmitting mothers (n = 16 viruses), and seven postnatally-infected infants (n = 7 postnatally-transmitted/founder (T/F) viruses). RESULTS: There was no difference in the efficiency of epithelial cell interactions between Env virus variants from the breast milk of transmitting and nontransmitting mothers. Moreover, there was similar efficiency of DC-mediated trans-infection, CCR5-usage, target cell fusion, and infectivity between HIV-1 Env-pseudoviruses from nontransmitting mothers and postnatal T/F viruses. Milk Env-pseudoviruses were generally sensitive to neutralization by autologous maternal plasma and resistant to breast milk neutralization. Infant T/F Env-pseudoviruses were equally sensitive to neutralization by broadly-neutralizing monoclonal and polyclonal antibodies as compared to nontransmitted breast milk Env variants. CONCLUSION: Postnatally-T/F Env variants do not appear to possess a superior ability to interact with and cross a mucosal barrier or an exceptional resistance to neutralization that define their capability to initiate infection across the infant gastrointestinal tract in the setting of preexisting maternal antibodies.

Do You Want to Hear the Bad News? The Value of Diagnostic Tests for Alzheimer's Disease.

OBJECTIVE: The diagnosis of Alzheimer's disease (AD) remains difficult. Lack of diagnostic certainty or possible distress related to a positive result from diagnostic testing could limit the application of new testing technologies. The objective of this paper is to quantify respondents' preferences for obtaining AD diagnostic tests and to estimate the perceived value of AD test information. METHODS: Discrete-choice experiment and contingent-valuation questions were administered to respondents in Germany and the United Kingdom. Choice data were analyzed by using random-parameters logit. A probit model characterized respondents who were not willing to take a test. RESULTS: Most respondents indicated a positive value for AD diagnostic test information. Respondents who indicated an interest in testing preferred brain imaging without the use of radioactive markers. German respondents had relatively lower money-equivalent values for test features compared with respondents in the United Kingdom. CONCLUSIONS: Respondents preferred less invasive diagnostic procedures and tests with higher accuracy and expressed a willingness to pay up to €700 to receive a less invasive test with the highest accuracy.

Heparin-binding hemagglutinin, from an extrapulmonary dissemination factor to a powerful diagnostic and protective antigen against tuberculosis.

Interactions of Mycobacterium tuberculosis with macrophages have long been recognized to be crucial to the pathogenesis of tuberculosis. The role of non-phagocytic cells is less well known. We have discovered a M. tuberculosis surface protein that interacts specifically with non-phagocytic cells, expresses hemagglutination activity and binds to sulfated glycoconjugates. It is therefore called heparin-binding hemagglutinin (HBHA). HBHA-deficient M. tuberculosis mutant strains are significantly impaired in their ability to disseminate from the lungs to other tissues, suggesting that the interaction with non-phagocytic cells, such as pulmonary epithelial cells, may play an important role in the extrapulmonary dissemination of the tubercle bacillus, one of the key steps that may lead to latency. Latently infected human individuals mount a strong T cell response to HBHA, whereas patients with active disease do not, suggesting that HBHA is a good marker for the immunodiagnosis of latent tuberculosis, and that HBHA-specific Th1 responses may contribute to protective immunity against active tuberculosis. Strong HBHA-mediated immuno-protection was shown in mouse challenge models. HBHA is a methylated protein and its antigenicity in latently infected subjects, as well as its protective immunogenicity strongly depends on the methylation pattern of HBHA. In both mice and man, the HBHA-specific IFN-gamma was produced by both the CD4(+) and the CD8(+) T cells. Furthermore, the HBHA-specific CD8(+) T cells expressed bactericidal and cytotoxic activities to mycobacteria-infected macrophages. This latter activity is most likely perforin mediated. Together, these observations strongly support the potential of methylated HBHA as an important component in future, acellular vaccines against tuberculosis.

Methylation-dependent T cell immunity to Mycobacterium tuberculosis heparin-binding hemagglutinin.

Although post-translational modifications of protein antigens may be important componenets of some B cell epitopes, the determinants of T cell immunity are generally nonmodified peptides. Here we show that methylation of the Mycobacterium tuberculosis heparin-binding hemagglutinin (HBHA) by the bacterium is essential for effective T cell immunity to this antigen in infected healthy humans and in mice. Methylated HBHA provides high levels of protection against M. tuberculosis challenge in mice, whereas nonmethylated HBHA does not. Protective immunity induced by methylated HBHA is comparable to that afforded by vaccination with bacille Calmette et Guérin, the only available anti-tuberculosis vaccine. Thus, post-translational modifications of proteins may be crucial for their ability to induce protective T cell-mediated immunity against infectious diseases such as tuberculosis.

Flo/Stress: an integrated software module to predict stress in electronic products

Software technology that predicts stress in electronic systems and packages, developed as part of TCS Programme, is described. The software is closely integrated within a thermal design tool providing the ability to simulate the coupled effects of airflow, temperature and stress on product performance. This integrated approach to analysis will help decrease the number of design cycles.

The same but different – how to introduce variation within computing assessment tasks

In this article, suggestions are made for introducing an individual element into formative assessment of the ability to use computer software for statistics.

An integrated approach to flow, thermal and mechanical modeling of electronics devices

The future success of many electronics companies will depend to a large extent on their ability to initiate techniques that bring schedules, performance, tests, support, production, life-cycle-costs, reliability prediction and quality control into the earliest stages of the product creation process. Earlier papers have discussed the benefits of an integrated analysis environment for system-level thermal, stress and EMC prediction. This paper focuses on developments made to the stress analysis module and presents results obtained for an SMT resistor. Lifetime predictions are made using the Coffin-Manson equation. Comparison with the creep strain energy based models of Darveaux (1997) shows the shear strain based method to underestimate the solder joint life. Conclusions are also made about the capabilities of both approaches to predict the qualitative and quantitative impact of design changes.

Using computer models to identify optimal conditions for flip-chip assembly and reliability

Flip-chip assembly, developed in the early 1960s, is now being positioned as a key joining technology to achieve high-density mounting of electronic components on to printed circuit boards for high-volume, low-cost products. Computer models are now being used early within the product design stage to ensure that optimal process conditions are used. These models capture the governing physics taking place during the assembly process and they can also predict relevant defects that may occur. Describes the application of computational modelling techniques that have the ability to predict a range of interacting physical phenomena associated with the manufacturing process. For example, in the flip-chip assembly process we have solder paste deposition, solder joint shape formation, heat transfer, solidification and thermal stress. Illustrates the application of modelling technology being used as part of a larger UK study aiming to establish a process route for high-volume, low-cost, sub-100-micron pitch flip-chip assembly.

Performance and reliability of flexible substrates when subjected to lead-free processing

The use of flexible substrates is growing in many applications such as computer peripherals, hand held devices, telecommunications, automotive, aerospace, etc. The drive to adopt flexible circuits is due to their ability to reduce size, weight, assembly time and cost of the final product.They also accommodate flexibility by allowing relative movement between component parts and provide a route for three dimensional packaging. This paper will describe some of the current research results from the Flex-No-Lead project, a European Commission sponsored research program. The principle aim of this project is to investigate the processing, performance, and reliability of flexible substrates when subjected to new environmentally friendly, lead-free soldering technologies. This paper will discuss the impact of specific design variables on performance and reliability. In particular the paper will focus on copper track designs, substrate material, dielectric material and solder-mask defined joints.

An architectural approach to autonomics and self-management of automotive embedded electronic systems

Embedded electronic systems in vehicles are of rapidly increasing commercial importance for the automotive industry. While current vehicular embedded systems are extremely limited and static, a more dynamic configurable system would greatly simplify the integration work and increase quality of vehicular systems. This brings in features like separation of concerns, customised software configuration for individual vehicles, seamless connectivity, and plug-and-play capability. Furthermore, such a system can also contribute to increased dependability and resource optimization due to its inherent ability to adjust itself dynamically to changes in software, hardware resources, and environment condition. This paper describes the architectural approach to achieving the goals of dynamically self-configuring automotive embedded electronic systems by the EU research project DySCAS. The architecture solution outlined in this paper captures the application and operational contexts, expected features, middleware services, functions and behaviours, as well as the basic mechanisms and technologies. The paper also covers the architecture conceptualization by presenting the rationale, concerning the architecture structuring, control principles, and deployment concept. In this paper, we also present the adopted architecture V&V strategy and discuss some open issues in regards to the industrial acceptance.

Challenges to Slovakia and Poland health policy decisions: use of investment treaties to claim compensation for reversal of privatisation/liberalisation policies

Investment treaties, and possibly the EU Treaty itself, are being used by multinational companies Penta and Eureko to try and force the Slovak government to pay compensation for reversing health privatisation and liberalisation policies. Similar action has been used against the Polish government by Eureko to win compensation worth nearly 2 billion Euros and a policy commitment to further privatisation.