An Efficient Normalisation Procedure for Linear Temporal Logic and Very Weak Alternating Automata

In the mid 80s, Lichtenstein, Pnueli, and Zuck proved a classical theorem stating that every formula of Past LTL (the extension of LTL with past operators) is equivalent to a formula of the form $\bigwedge_{i=1}^n \mathbf{G}\mathbf{F} \varphi_i \vee \mathbf{F}\mathbf{G} \psi_i$, where $\varphi_i$ and $\psi_i$ contain only past operators. Some years later, Chang, Manna, and Pnueli built on this result to derive a similar normal form for LTL. Both normalisation procedures have a non-elementary worst-case blow-up, and follow an involved path from formulas to counter-free automata to star-free regular expressions and back to formulas. We improve on both points. We present a direct and purely syntactic normalisation procedure for LTL yielding a normal form, comparable to the one by Chang, Manna, and Pnueli, that has only a single exponential blow-up. As an application, we derive a simple algorithm to translate LTL into deterministic Rabin automata. The algorithm normalises the formula, translates it into a special very weak alternating automaton, and applies a simple determinisation procedure, valid only for these special automata.Comment: This is the extended version of the referenced conference paper and contains an appendix with additional materia

Effect of a contact lens on mouse retinal in vivo imaging: Effective focal length changes and monochromatic aberrations

For in vivo mouse retinal imaging, especially with Adaptive Optics instruments, application of a contact lens is desirable, as it allows maintenance of cornea hydration and helps to prevent cataract formation during lengthy imaging sessions. However, since the refractive elements of the eye (cornea and lens) serve as the objective for most in vivo retinal imaging systems, the use of a contact lens, even with 0 Dpt. refractive power, can alter the system's optical properties. In this investigation we examined the effective focal length change and the aberrations that arise from use of a contact lens. First, focal length changes were simulated with a Zemax mouse eye model. Then ocular aberrations with and without a 0 Dpt. contact lens were measured with a Shack-Hartmann wavefront sensor (SHWS) in a customized AO-SLO system. Total RMS wavefront errors were measured for two groups of mice (14-month, and 2.5-month-old), decomposed into 66 Zernike aberration terms, and compared. These data revealed that vertical coma and spherical aberrations were increased with use of a contact lens in our system. Based on the ocular wavefront data we evaluated the effect of the contact lens on the imaging system performance as a function of the pupil size. Both RMS error and Strehl ratios were quantified for the two groups of mice, with and without contact lenses, and for different input beam sizes. These results provide information for determining optimum pupil size for retinal imaging without adaptive optics, and raise critical issues for design of mouse optical imaging systems that incorporate contact lenses

Permanent Lattice Compression of Lead-Halide Perovskite for Persistently Enhanced Optoelectronic Properties

Under mild mechanical pressure, halide perovskites show enhanced optoelectronic properties. However, these improvements are reversible upon decompression, and permanent enhancements have yet to be ..

The rapid size- and shape-controlled continuous hydrothermal synthesis of metal sulphide nanomaterials

Continuous flow hydrothermal synthesis offers a cheap, green and highly scalable route for the preparation of inorganic nanomaterials which has predominantly been applied to metal oxide based materials. In this work we report the first continuous flow hydrothermal synthesis of metal sulphide nanomaterials. A wide range of binary metal sulphides, ZnS, CdS, PbS, CuS, Fe₍₁₋ᵪ₎S and Bi₂S₃, have been synthesised. By varying the reaction conditions two different mechanisms may be invoked; a growth dominated route which permits the formation of nanostructured sulphide materials, and a nucleation driven process which produces nanoparticles with temperature dependent size control. This offers a new and industrially viable route to a wide range of metal sulphide nanoparticles with facile size and shape control

A density functional theory based analysis of photoinduced electron transfer in a triazacryptand based K+ sensor

The electronic structure and photoinduced electron transfer processes in a K+ fluorescent sensor that comprises a 4-amino-naphthalimide derived fluorophore with a triazacryptand lig- and is investigated using density functional theory (DFT) and time-dependent density functional theory (TDDFT) in order to rationalise the function of the sensor. The absorption and emission energies of the intense electronic excitation localised on the fluorophore are accurately described using a ∆SCF Kohn-Sham DFT approach, which gives excitation energies closer to experiment than TDDFT. Analysis of the molecular orbital diagram arising from DFT calculations for the isolated molecule or with implicit solvent cannot account for the function of the sensor and it is necessary to consider the relative energies of the electronic states formed from the local excitation on the fluorophore and the lowest fluorophore→chelator charge transfer state. The inclusion of solvent in these calculations is critical since the strong interaction of the charge transfer state with the solvent lowers it energy below the local fluorophore excited state making a reductive photoinduced electron transfer possible in the absence of K+, while no such process is possible when the sensor is bound to K+. The rate of electron transfer is quantified using Marcus theory, which gives a rate of electron transfer of k_ET=5.98 x 10^6 s−1

Multiparameter Phospho-Flow Analysis of Lymphocytes in Early Rheumatoid Arthritis: Implications for Diagnosis and Monitoring Drug Therapy

The precise mechanisms involved in the initiation and progression of rheumatoid arthritis (RA) are not known. Early stages of RA often have non-specific symptoms, delaying diagnosis and therapy. Additionally, there are currently no established means to predict clinical responsiveness to therapy. Immune cell activation is a critical component therefore we examined the cellular activation of peripheral blood mononuclear cells (PBMCs) in the early stages of RA, in order to develop a novel diagnostic modality.PBMCs were isolated from individuals diagnosed with early RA (ERA) (n = 38), longstanding RA (n = 10), osteoarthritis (OA) (n = 19) and from healthy individuals (n = 10). PBMCs were examined for activation of 15 signaling effectors, using phosphorylation status as a measure of activation in immunophenotyped cells, by flow cytometry (phospho-flow). CD3+CD4+, CD3+CD8+ and CD20+ cells isolated from patients with ERA, RA and OA exhibited activation of multiple phospho-epitopes. ERA patient PBMCs showed a bias towards phosphorylation-activation in the CD4+ and CD20+ compartments compared to OA PBMCs, where phospho-activation was primarily observed in CD8+ cells. The ratio of phospho (p)-AKT/p-p38 was significantly elevated in patients with ERA and may have diagnostic potential. The mean fluorescent intensity (MFI) levels for p-AKT and p-H3 in CD4+, CD8+ and CD20+ T cells correlated directly with physician global assessment scores (MDGA) and DAS (disease activity score). Stratification by medications revealed that patients receiving leflunomide, systemic steroids or anti-TNF therapy had significant reductions in phospho-specific activation compared with patients not receiving these therapies. Correlative trends between medication-associated reductions in the levels of phosphorylation of specific signaling effectors and lower disease activity were observed.Phospho-flow analysis identified phosphorylation-activation of specific signaling effectors in the PB from patients with ERA. Notably, phosphorylation of these signaling effectors did not distinguish ERA from late RA, suggesting that the activation status of discrete cell populations is already established early in disease. However, when the ratio of MFI values for p-AKT and p-p38 is >1.5, there is a high likelihood of having a diagnosis of RA. Our results suggest that longitudinal sampling of patients undergoing therapy may result in phospho-signatures that are predictive of drug responsiveness