Exceptional points in the thermoacoustic spectrum

Exceptional points are found in the spectrum of a prototypical thermoacoustic system as the parameters of the flame transfer function are varied. At these points, two eigenvalues and the associated eigenfunctions coalesce. The system's sensitivity to changes in the parameters becomes infinite. Two eigenvalue branches collide at the exceptional point as the interaction index is increased. One branch originates from a purely acoustic mode, whereas the other branch originates from an intrinsic thermoacoustic mode. The existence of exceptional points in thermoacoustic systems has implications for physical understanding, computing, modeling and control

Use of a novel Förster resonance energy transfer method to identify locations of site-bound metal ions in the U2–U6 snRNA complex

U2 and U6 snRNAs pair to form a phylogenetically conserved complex at the catalytic core of the spliceosome. Interactions with divalent metal ions, particularly Mg(II), at specific sites are essential for its folding and catalytic activity. We used a novel Förster resonance energy transfer (FRET) method between site-bound luminescent lanthanide ions and a covalently attached fluorescent dye, combined with supporting stoichiometric and mutational studies, to determine locations of site-bound Tb(III) within the human U2–U6 complex. At pH 7.2, we detected three metal-ion-binding sites in: (1) the consensus ACACAGA sequence, which forms the internal loop between helices I and III; (2) the four-way junction, which contains the conserved AGC triad; and (3) the internal loop of the U6 intra-molecular stem loop (ISL). Binding at each of these sites is supported by previous phosphorothioate substitution studies and, in the case of the ISL site, by NMR. Binding of Tb(III) at the four-way junction and the ISL sites was found to be pH-dependent, with no ion binding observed below pH 6 and 7, respectively. This pH dependence of metal ion binding suggests that the local environment may play a role in the binding of metal ions, which may impact on splicing activity

Variability in disease phenotypes within a single PRNP genotype suggests the existence of multiple natural sheep scarpie strains within Europe

Variability of pathological phenotypes within classical sheep scrapie cases has been reported for some time, but in many instances it has been attributed to differences in the PRNP genotype of the host. To address this issue we have examined by immunohistochemistry (IHC) and Western blotting (WB) for the disease-associated form of the prion protein (PrPd), the brains of 23 sheep from five European countries, all of which were of the same ARQ/ARQ genotype. As a result of IHC examinations, sheep were distributed into five groups with different phenotypes and the groups were the same regardless of the scoring method used, ‘long’ or ‘short’ PrPd profiling. The groups made did not respond to the geographical origin of the cases and did not correlate with the vacuolar lesion profiles, which showed a high individual variability. Discriminatory IHC and WB methods coincided to detect a ‘CH1641-like’ case but otherwise correlated poorly in the classification of disease phenotypes. No other polymorphisms of the PRNP gene were found that could account for the pathological differences, except perhaps for a sheep from Spain with a mutation at codon 103 and a unique pathological phenotype. Preliminary evidence indicates that those different IHC phenotypes correlate with distinct biological properties on bioassay, suggesting that they are indicative of strain diversity. We therefore conclude that natural scrapie strains exist and that they can be revealed by detailed pathological examinations, which can be harmonized between laboratories to produce comparable results

A Process Framework for Designing Software Reference Architectures for Providing Tools as a Service

Product-Focused Software Process ImprovementSoftware Reference Architecture (SRA), which is a generic architecture solution for a specific type of software systems, provides foundation for the design of concrete architectures in terms of architecture design guidelines and architecture elements. The complexity and size of certain types of software systems need customized and systematic SRA design and evaluation methods. In this paper, we present a software Reference Architecture Design process Framework (RADeF) that can be used for analysis, design and evaluation of the SRA for provisioning of Tools as a Service as part of a cloud-enabled workSPACE (TSPACE). The framework is based on the state of the art results from literature and our experiences with designing software architectures for cloud-based systems. We have applied RADeF SRA design two types of TSPACE: software architecting TSPACE and software implementation TSPACE. The presented framework emphasizes on keeping the conceptual meta-model of the domain under investigation at the core of SRA design strategy and use it as a guiding tool for design, evaluation, implementation and evolution of the SRA. The framework also emphasizes to consider the nature of the tools to be provisioned and underlying cloud platforms to be used while designing SRA. The framework recommends adoption of the multi-faceted approach for evaluation of SRA and quantifiable measurement scheme to evaluate quality of the SRA. We foresee that RADeF can facilitate software architects and researchers during design, application and evaluation of a SRA and its instantiations into concrete software systems.Muhammad Aufeef Chauhan, Muhammad Ali Babar, and Christian W. Probs