Postfreeze reduction of locomotor endurance in the freeze-tolerant wood frog, Rana sylvatica.

Considerable study has focused on the physiological adaptations for freeze tolerance in the wood frog, Rana sylvatica, a northern species that overwinters within the frost zone, but little attention has been paid to the associated costs to organismal performance. Here we report that freezing causes transient impairment of locomotor endurance and adverse changes in exercise physiology that persist for at least 96 h. Wood frogs frozen at −2°C for 36 h exhibited normal behaviors and hydro‐osmotic status and near‐normal metabolite (glycogen, glucose, and lactate) levels within 24 h after thawing began. However, when exercised to exhaustion on a treadmill, these frogs showed a 40% reduction in endurance as compared to sham‐treated (unfrozen) controls, a reduction that persisted for at least 96 h. Previously frozen frogs exhibited higher rates of lactate accumulation during exercise than controls, suggesting that prior freezing forces greater reliance on the glycolytic pathways of energy production to support exercise. Given that this species breeds in late winter, when subzero temperatures are common, freezing may result in reduced fitness by hampering their ability to reach the pond, avoid predators, and successfully obtain mates

A New Method for Searching for Free Fractional Charge Particles in Bulk Matter

We present a new experimental method for searching for free fractional charge in bulk matter; this new method derives from the traditional Millikan liquid drop method, but allows the use of much larger drops, 20 to 100 mm in diameter, compared to the traditional method that uses drops less than 15 mm in diameter. These larger drops provide the substantial advantage that it is then much easier to consistently generate drops containing liquid suspensions of powdered meteorites and other special minerals. These materials are of great importance in bulk searches for fractional charge particles that may have been produced in the early universe.Comment: 17 pages, 5 figures in a singl PDF file (created from WORD Doc.). Submitted to Review of Scientific Instrument

New Light-Travel Time Models and Orbital Stability Study of the Proposed Planetary System HU Aquarii

In this work we propose a new orbital architecture for the two proposed circumbinary planets around the polar eclipsing binary HU Aquarii. We base the new two-planet, light-travel time model on the result of a Monte Carlo simulation driving a least-squares Levenberg-Marquardt minimisation algorithm on the observed eclipse egress times. Our best-fitting model with $\chi_{r}^2=1.43$ resulted in high final eccentricities for the two companions leading to an unstable orbital configuration. From a large ensemble of initial guesses we examined the distribution of final eccentricities and semi-major axes for different $\chi_{r}^2$ parameter intervals and encountered qualitatively a second population of best-fitting parameters. The main characteristic of this population is described by low-eccentric orbits favouring long-term orbital stability of the system. We present our best-fitting model candidate for the proposed two-planet system and demonstrate orbital stability over one million years using numerical integrations.Comment: 9 Figures (B/W) and 2 tables, accepted for publication in MNRAS, this is pre-proof versio

PAHs in the Halo of NGC 5529

We present sensitive ISO $\lambda 6.7 \mu$m observations of the edge-on galaxy, NGC 5529, finding an extensive MIR halo around NGC 5529. The emission is dominated by PAHs in this band. The PAH halo has an exponential scale height of 3.7 kpc but can still be detected as far as $\approx 10$ kpc from the plane to the limits of the high dynamic range (1770/1) data. This is the most extensive PAH halo yet detected in a normal galaxy. This halo shows substructure and the PAHs likely originate from some type of disk outflow. PAHs are long-lived in a halo environment and therefore continuous replenishment from the disk is not required (unless halo PAHs are also being destroyed or removed), consistent with the current low SFR of the galaxy. The PAHs correlate spatially with halo H$\alpha$ emission, previously observed by Miller & Veilleux (2003); both components are likely excited/ionized by in-disk photons that are leaking into the halo. The presence of halo gas may be related to the environment of NGC 5529 which contains at least 17 galaxies in a small group of which NGC 5529 is the dominant member. Of these, we have identified two new companions from the SDSS.Comment: 16 pages, 5 gif figures, accepted for publication in A&A, For pdf with higher quality figures, see http://www.astro.queensu.ca/~irwi

Chemical informatics uncovers a new role for moexipril as a novel inhibitor of cAMP phosphodiesterase-4 (PDE4)

PDE4 is one of eleven known cyclic nucleotide phosphodiesterase families and plays a pivotal role in mediating hydrolytic degradation of the important cyclic nucleotide second messenger, cyclic 3′5′ adenosine monophosphate (cAMP). PDE4 inhibitors are known to have anti-inflammatory properties, but their use in the clinic has been hampered by mechanism-associated side effects that limit maximally tolerated doses. In an attempt to initiate the development of better-tolerated PDE4 inhibitors we have surveyed existing approved drugs for PDE4-inhibitory activity. With this objective, we utilised a high-throughput computational approach that identified moexipril, a well tolerated and safe angiotensin-converting enzyme (ACE) inhibitor, as a PDE4 inhibitor. Experimentally we showed that moexipril and two structurally related analogues acted in the micro molar range to inhibit PDE4 activity. Employing a FRET-based biosensor constructed from the nucleotide binding domain of the type 1 exchange protein activated by cAMP, EPAC1, we demonstrated that moexipril markedly potentiated the ability of forskolin to increase intracellular cAMP levels. Finally, we demonstrated that the PDE4 inhibitory effect of moexipril is functionally able to induce phosphorylation of the Hsp20 by cAMP dependent protein kinase A. Our data suggest that moexipril is a bona fide PDE4 inhibitor that may provide the starting point for development of novel PDE4 inhibitors with an improved therapeutic window

Quantisation of Monopoles with Non-abelian Magnetic Charge

Magnetic monopoles in Yang-Mills-Higgs theory with a non-abelian unbroken gauge group are classified by holomorphic charges in addition to the topological charges familiar from the abelian case. As a result the moduli spaces of monopoles of given topological charge are stratified according to the holomorphic charges. Here the physical consequences of the stratification are explored in the case where the gauge group SU(3) is broken to U(2). The description due to A. Dancer of the moduli space of charge two monopoles is reviewed and interpreted physically in terms of non-abelian magnetic dipole moments. Semi-classical quantisation leads to dyonic states which are labelled by a magnetic charge and a representation of the subgroup of U(2) which leaves the magnetic charge invariant (centraliser subgroup). A key result of this paper is that these states fall into representations of the semi-direct product U(2) \semidir R^4. The combination rules (Clebsch-Gordan coefficients) of dyonic states can thus be deduced. Electric-magnetic duality properties of the theory are discussed in the light of our results, and supersymmetric dyonic BPS states which fill the SL(2,Z)-orbit of the basic massive W-bosons are found.Comment: 57 pages, harvmac, amssym, two eps figures, minor mistakes and typos corrected, references added; to appear in Nucl. Phys.