Asymptotic silence-breaking singularities

We discuss three complementary aspects of scalar curvature singularities: asymptotic causal properties, asymptotic Ricci and Weyl curvature, and asymptotic spatial properties. We divide scalar curvature singularities into two classes: so-called asymptotically silent singularities and non-generic singularities that break asymptotic silence. The emphasis in this paper is on the latter class which have not been previously discussed. We illustrate the above aspects and concepts by describing the singularities of a number of representative explicit perfect fluid solutions.Comment: 25 pages, 6 figure

Asymptotic self-similarity breaking at late times in cosmology

We study the late time evolution of a class of exact anisotropic cosmological solutions of Einstein's equations, namely spatially homogeneous cosmologies of Bianchi type VII$_0$ with a perfect fluid source. We show that, in contrast to models of Bianchi type VII$_h$ which are asymptotically self-similar at late times, Bianchi VII$_0$ models undergo a complicated type of self-similarity breaking. This symmetry breaking affects the late time isotropization that occurs in these models in a significant way: if the equation of state parameter $\gamma$ satisfies $\gamma \leq 4/3$ the models isotropize as regards the shear but not as regards the Weyl curvature. Indeed these models exhibit a new dynamical feature that we refer to as Weyl curvature dominance: the Weyl curvature dominates the dynamics at late times. By viewing the evolution from a dynamical systems perspective we show that, despite the special nature of the class of models under consideration, this behaviour has implications for more general models.Comment: 29 page

Phenothiazinium photosensitisers XI. Improved toluidine blue photoantimicrobials.

The phenothiazinium derivative toluidine blue O (TBO) is widely employed as a photoantimicrobial agent in clinical trialling, particularly in dentistry. However, its activity against a range of pathogenic microbial species is not significantly different to that of the standard photoantimicrobial methylene blue. In the current study, derivatives of TBO with varying hydrocarbon substitution in chromophore position 2 were synthesised via the established anilinethiosulphonic route, using the mild oxidant silver(II) carbonate to allow substituent preservation. The resulting series of analogues demonstrated the expected increases in visible absorption wavelength and lipophilicity with increasing hydrocarbon content, as well as decreased aggregation for derivatives with bulkier substituents, and all produced singlet oxygen on illumination in vitro. Screening against a range of bacterial and fungal pathogens relevant to infection control showed remarkable increases in activity relative to the parent compound, particularly against the clinically important Gram-negative bacterium Pseudomonas aeruginosa. In addition, in order to demonstrate clinical relevance, the photoactivities of the new derivatives against microbial targets were compared to conventional antibacterial and antifungal drugs, as well as biocides commonly used for local disinfection. Activity here was also generally greater than that of the conventional agents used for comparison, considerably so relative to the local disinfectant agents

Gravity Waves from a Cosmological Phase Transition: Gauge Artifacts and Daisy Resummations

The finite-temperature effective potential customarily employed to describe the physics of cosmological phase transitions often relies on specific gauge choices, and is manifestly not gauge-invariant at finite order in its perturbative expansion. As a result, quantities relevant for the calculation of the spectrum of stochastic gravity waves resulting from bubble collisions in first-order phase transitions are also not gauge-invariant. We assess the quantitative impact of this gauge-dependence on key quantities entering predictions for gravity waves from first order cosmological phase transitions. We resort to a simple abelian Higgs model, and discuss the case of R_xi gauges. By comparing with results obtained using a gauge-invariant Hamiltonian formalism, we show that the choice of gauge can have a dramatic effect on theoretical predictions for the normalization and shape of the expected gravity wave spectrum. We also analyze the impact of resumming higher-order contributions as needed to maintain the validity of the perturbative expansion, and show that doing so can suppress the amplitude of the spectrum by an order of magnitude or more. We comment on open issues and possible strategies for carrying out "daisy resummed" gauge invariant computations in non-Abelian models for which a gauge-invariant Hamiltonian formalism is not presently available.Comment: 25 pages, 10 figure

Kinematics of women's sprint canoeing technique

Little is known about the biomechanics of sprint canoeing, especially for women’s canoeing, and a quantitative kinematic description of the motion would help coaches to develop valid technique coaching models. Five highly-trained female canoeists were filmed at 150 Hz while undertaking a 50 s maximal effort on a canoe ergometer, whose trolley motions were taken to represent those of the boat. Selected boat, body and paddle kinematics were evaluated at three key stroke cycle events (Contact, Paddle Vertical, and End of Drive) and their patterns monitored across the stroke cycle. While no clear trends between the kinematics and power output emerged, a range of strategies were identified and the data represent an initial step in the construction of detailed technique models that can be used to evaluate and monitor individual athletes

An almost isotropic cosmic microwave temperature does not imply an almost isotropic universe

In this letter we will show that, contrary to what is widely believed, an almost isotropic cosmic microwave background (CMB) temperature does not imply that the universe is ``close to a Friedmann-Lemaitre universe''. There are two important manifestations of anisotropy in the geometry of the universe, (i) the anisotropy in the overall expansion, and (ii) the intrinsic anisotropy of the gravitational field, described by the Weyl curvature tensor, although the former usually receives more attention than the latter in the astrophysical literature. Here we consider a class of spatially homogeneous models for which the anisotropy of the CMB temperature is within the current observational limits but whose Weyl curvature is not negligible, i.e. these models are not close to isotropy even though the CMB temperature is almost isotropic.Comment: 5 pages (AASTeX, aaspp4.sty), submitted to Astrophysical Journal Letter

Human osteoarthritis synovium contains an alternatively spliced transcript of ADAMTS4

Purpose: The characterization of an alternatively spliced transcript of the ADAMTS4 aggrecanase. Methods: In human OA synovial cell cultures, RT-PCR was performed using oligonucleotide primers designed to amplify across the exon 8/9 region of human ADAMTS4. The PCR products were purified using a QIAquick purification kit (Qiagen) and sequenced using in house facilities. A pCEP4 (Invitrogen) mammalian expression vector containing ADAMTS4 plus a FLAG epitope was mutated using the QuikChange II site directed mutagenesis kit (Stratagene) to contain the ADAMTS4 splice variant plus a FLAG epitope. The recombinant proteins were purified from HEK293 transfected cells using Anti-FLAG M2 affinity gel (Sigma). Polyclonal antibodies were raised against synthetic peptides representing sequences within the C-terminal region of the splice variant of ADAMTS4 and the raised antibodies were characterized using the recombinant splice variant of ADAMTS4. The antibodies were used in immunohistochemical analysis of human osteoarthritic synovium. The proteolysis of aggrecan and other proteoglycans by the recombinant spice variant of ADAMTS4 was investigated. Results: The degradation of aggrecan is mainly mediated by the aggrecanases, of which ADAMTS4 (aggrecanase-1) and ADAMTS5 (aggrecanase-2) are the best known. We here characterize an alternative splice variant of ADAMTS4. RT-PCR performed as described above resulted in the amplification of normal ADAMTS4, and also a smaller product missing 161 base pairs from the 5’ end of exon 9, the result of alternative splicing in which exon 8 joins to a cryptic 3’ splice site within exon 9. The protein produced by this alternative splicing would lack the spacer domain and have a C-terminus lacking any homologies with the normal ADAMTS4 spacer domain. The alternatively spliced transcript of ADAMTS4 was found in cultured OA synovial cells and in freshly digested OA synovium, but not in human brain, cervix or lung, or in normal bovine synovium. The protein synthesized from this alternatively spliced transcript of ADAMTS4 would lose functions dependent on its spacer domain, like substrate and matrix binding, and inhibition through fibronectin. Removal of the spacer domain from ADAMTS4 has been reported to increase its ability to cleave aggrecan at the Glu373-Ala374 bond, and it may well be that the alternatively spliced transcript produces a protein that is secreted in a more active form. HEK293 cells transfected with a pCEP4 vector containing the cDNA sequence of the splice variant of ADAMTS4 produced the corresponding protein in both the pro and active form. This protein could be found in the media, but mostly associated with the cells, as confirmed using antibodies specific for the splice variant that were produced using synthetic peptides. Immunohistochemical analysis of osteoarthritic synovium using these antibodies showed staining of cells within the synovium. Proteins purified by immunoprecipitation by Anti-FLAG M2 affinity gel from transfected and untransfected HEK293 cells were analysed using the ANASpec SensoLyte 520 Aggrecanase I assay kit. The splice variant had aggrecanase activity comparable to a commercially available ADAMTS4. The splice variant cleaved aggrecan at the G1u373-A1a374 site, as assessed by the neoepitope monoclonal antibody BC3, with activity comparable to ADAMTS4. Conclusions: ADAMTS4 is regulated at multiple levels through control of gene expression, mRNA splicing and protein processing, as well as the expression of naturally occurring inhibitors. We here describe the characteristics of the first known splice variant of ADAMTS4. This alternative splice transcript of ADAMTS4 is expressed as a protein in vivo and can be found in the synovium. It can be speculated that the changes in the C-terminal domain of the protein resulting from this alternatively spliced transcript would have changes in its substrate specificity. The protein produced by the alternative spliced transcript of ADAMTS4 has aggrecanase activity, and the release of low levels of this fully active variant of ADAMTS4 might be a factor in the slow process of superficial zone aggrecan loss in osteoarthritis

G_2 cosmological models separable in non-comoving coordinates

We study new separable orthogonally transitive abelian G_2 on S_2 models with two mutually orthogonal integrable Killing vector fields. For this purpose we consider separability of the metric functions in a coordinate system in which the velocity vector field of the perfect fluid does not take its canonical form, providing thereby solutions which are non-separable in comoving coordinates in general. Some interesting general features concerning this class of solutions are given. We provide a full classification for these models and present several families of explicit solutions with their properties.Comment: latex, 26 pages, accepted for publication in Class. Quantum Gra