Heterotopic heart transplantation in the rat receiving FK-506 alone or with cyclosporine.

In rats, FK significantly prolonged heterotopic heart graft survival over a wide dose range when given for 2 weeks starting on the day of the operation. Brief courses of FK for one to four days preoperatively, and especially beginning four days postoperatively, allowed long subsequent survival of heart grafts in otherwise untreated recipients. The seeming acceptance of the grafts with postoperative FK treatment was largely but not exclusively donor specific when tested eight days after the last FK dose by second grafts from the same donor v third-party donor grafts. FK in minimally therapeutic doses was synergistic with suboptimal doses of CyA

Three-loop matching coefficients for hot QCD: Reduction and gauge independence

We perform an integral reduction for the 3-loop effective gauge coupling and screening mass of QCD at high temperatures, defined as matching coefficients appearing in the dimensionally reduced effective field theory (EQCD). Expressing both parameters in terms of a set master (sum-) integrals, we show explicit gauge parameter independence. The lack of suitable methods for solving the comparatively large number of master integrals forbids the complete evaluation at the moment. Taking one generic class of masters as an example, we highlight the calculational techniques involved. The full result would allow to improve on one of the classic probes for the convergence of the weak-coupling expansion at high temperatures, namely the comparison of full and effective theory determinations of the spatial string tension. Furthermore, the full result would also allow to determine one new contribution of order O(g**7) to the pressure of hot QCD.Comment: 19 pages, 2 figures. v2: new Section 6 discussing applications, to match journal versio

The role of exponential asymptotics and complex singularities in self-similarity, transitions, and branch merging of nonlinear dynamics

We study a prototypical example in nonlinear dynamics where transition to self-similarity in a singular limit is fundamentally changed as a parameter is varied. Here, we focus on the complicated dynamics that occur in a generalised unstable thin-film equation that yields finite-time rupture. A parameter, n, is introduced to model more general disjoining pressures. For the standard case of van der Waals intermolecular forces, n = 3, it was previously established that a countably infinite number of self-similar solutions exist leading to rupture. Each solution can be indexed by a parameter, ϵ = ϵ1 > ϵ2 > · · · > 0, and the prediction of the discrete set of solutions requires examination of terms beyond-all-orders in ϵ. However, recent numerical results have demonstrated the surprising complexity that exists for general values of n. In particular, the bifurcation structure of self-similar solutions now exhibits branch merging as n is varied. In this work, we shall present key ideas of how branch merging can be interpreted via exponential asymptotics

Inhalation characteristics of asthma patients, COPD patients and healthy volunteers with the Spiromax® and Turbuhaler® devices: a randomised, cross-over study.

BACKGROUND: Spiromax® is a novel dry-powder inhaler containing formulations of budesonide plus formoterol (BF). The device is intended to provide dose equivalence with enhanced user-friendliness compared to BF Turbuhaler® in asthma and chronic obstructive pulmonary disease (COPD). The present study was performed to compare inhalation parameters with empty versions of the two devices, and to investigate the effects of enhanced training designed to encourage faster inhalation. METHODS: This randomised, open-label, cross-over study included children with asthma (n = 23), adolescents with asthma (n = 27), adults with asthma (n = 50), adults with COPD (n = 50) and healthy adult volunteers (n = 50). Inhalation manoeuvres were recorded with each device after training with the patient information leaflet (PIL) and after enhanced training using an In-Check Dial device. RESULTS: After PIL training, peak inspiratory flow (PIF), maximum change in pressure (∆P) and the inhalation volume (IV) were significantly higher with Spiromax than with the Turbuhaler device (p values were at least <0.05 in all patient groups). After enhanced training, numerically or significantly higher values for PIF, ∆P, IV and acceleration remained with Spiromax versus Turbuhaler, except for ∆P in COPD patients. After PIL training, one adult asthma patient and one COPD patient inhaled <30 L/min through the Spiromax compared to one adult asthma patient and five COPD patients with the Turbuhaler. All patients achieved PIF values of at least 30 L/min after enhanced training. CONCLUSIONS: The two inhalers have similar resistance so inhalation flows and pressure changes would be expected to be similar. The higher flow-related values noted for Spiromax versus Turbuhaler after PIL training suggest that Spiromax might have human factor advantages in real-world use. After enhanced training, the flow-related differences between devices persisted; increased flow rates were achieved with both devices, and all patients achieved the minimal flow required for adequate drug delivery. Enhanced training could be useful, especially in COPD patients

Minocycline treatment inhibits microglial activation and alters spinal levels of endocannabinoids in a rat model of neuropathic pain

Activation of spinal microglia contributes to aberrant pain responses associated with neuropathic pain states. Endocannabinoids (ECs) are present in the spinal cord, and inhibit nociceptive processing; levels of ECs may be altered by microglia which modulate the turnover of endocannabinoids in vitro. Here, we investigate the effect of minocycline, an inhibitor of activated microglia, on levels of the endocannabinoids anandamide and 2-arachidonoylglycerol (2-AG), and the related compound N-palmitoylethanolamine (PEA), in neuropathic spinal cord. Selective spinal nerve ligation (SNL) in rats resulted in mechanical allodynia and the presence of activated microglia in the ipsilateral spinal cord. Chronic daily treatment with minocycline (30 mg/kg, ip for 14 days) significantly reduced the development of mechanical allodynia at days 5, 10 and 14 post-SNL surgery, compared to vehicle-treated SNL rats (P < 0.001). Minocycline treatment also significantly attenuated OX-42 immunoreactivity, a marker of activated microglia, in the ipsilateral (P < 0.001) and contralateral (P < 0.01) spinal cord of SNL rats, compared to vehicle controls. Minocycline treatment significantly (P < 0.01) decreased levels of 2-AG and significantly (P < 0.01) increased levels of PEA in the ipsilateral spinal cord of SNL rats, compared to the contralateral spinal cord. Thus, activation of microglia affects spinal levels of endocannabinoids and related compounds in neuropathic pain states

Can a falling tree make a noise in two forests at the same time?

It is a commonplace to claim that quantum mechanics supports the old idea that a tree falling in a forest makes no sound unless there is a listener present. In fact, this conclusion is far from obvious. Furthermore, if a tunnelling particle is observed in the barrier region, it collapses to a state in which it is no longer tunnelling. Does this imply that while tunnelling, the particle can not have any physical effects? I argue that this is not the case, and moreover, speculate that it may be possible for a particle to have effects on two spacelike separate apparatuses simultaneously. I discuss the measurable consequences of such a feat, and speculate about possible statistical tests which could distinguish this view of quantum mechanics from a ``corpuscular'' one. Brief remarks are made about an experiment underway at Toronto to investigate these issues.Comment: 9 pp, Latex, 3 figs, to appear in Proc. Obsc. Unr. Conf.; Fig 2 postscript repaired on 26.10.9

Ligand Specificity of Group I Biotin Protein Ligase of Mycobacterium tuberculosis

BACKGROUND: Fatty acids are indispensable constituents of mycolic acids that impart toughness & permeability barrier to the cell envelope of M. tuberculosis. Biotin is an essential co-factor for acetyl-CoA carboxylase (ACC) the enzyme involved in the synthesis of malonyl-CoA, a committed precursor, needed for fatty acid synthesis. Biotin carboxyl carrier protein (BCCP) provides the co-factor for catalytic activity of ACC. METHODOLOGY/PRINCIPAL FINDINGS: BPL/BirA (Biotin Protein Ligase), and its substrate, biotin carboxyl carrier protein (BCCP) of Mycobacterium tuberculosis (Mt) were cloned and expressed in E. coli BL21. In contrast to EcBirA and PhBPL, the approximately 29.5 kDa MtBPL exists as a monomer in native, biotin and bio-5'AMP liganded forms. This was confirmed by molecular weight profiling by gel filtration on Superdex S-200 and Dynamic Light Scattering (DLS). Computational docking of biotin and bio-5'AMP to MtBPL show that adenylation alters the contact residues for biotin. MtBPL forms 11 H-bonds with biotin, relative to 35 with bio-5'AMP. Docking simulations also suggest that bio-5'AMP hydrogen bonds to the conserved 'GRGRRG' sequence but not biotin. The enzyme catalyzed transfer of biotin to BCCP was confirmed by incorporation of radioactive biotin and by Avidin blot. The K(m) for BCCP was approximately 5.2 microM and approximately 420 nM for biotin. MtBPL has low affinity (K(b) = 1.06x10(-6) M) for biotin relative to EcBirA but their K(m) are almost comparable suggesting that while the major function of MtBPL is biotinylation of BCCP, tight binding of biotin/bio-5'AMP by EcBirA is channeled for its repressor activity. CONCLUSIONS/SIGNIFICANCE: These studies thus open up avenues for understanding the unique features of MtBPL and the role it plays in biotin utilization in M. tuberculosis

Habitat and forage associations of a naturally colonising insect pollinator, the Tree Bumblebee Bombus hypnorum

Bumblebees (Bombus species) are major pollinators of commercial crops and wildflowers but factors affecting their abundance, including causes of recent population declines, remain unclear. Investigating the ecology of species with expanding ranges provides a potentially powerful means of elucidating these factors. Such species may also bring novel pollination services to their new ranges. We therefore investigated landscape-scale habitat use and foraging preferences of the Tree Bumblebee, B. hypnorum, a recent natural colonist that has rapidly expanded its range in the UK over the past decade. Counts of B. hypnorum and six other Bombus species were made in March-June 2012 within a mixed landscape in south-eastern Norfolk, UK. The extent of different landscape elements around each transect was quantified at three scales (250 m, 500 m and 1500 m). We then identified the landscape elements that best predicted the density of B. hypnorum and other Bombus species. At the best fitting scale (250 m), B. hypnorum density was significantly positively associated with extent of both urban and woodland cover and significantly negatively associated with extent of oilseed rape cover. This combination of landscape predictors was unique to B. hypnorum. Urban and woodland cover were associated with B. hypnorum density at three and two, respectively, of the three scales studied. Relative to other Bombus species, B. hypnorum exhibited a significantly higher foraging preference for two flowering trees, Crataegus monogyna and Prunus spinosa, and significantly lower preferences for Brassica napus, Glechoma hederacea and Lamium album. Our study provides novel, quantitative support for an association of B. hypnorum with urban and woodland landscape elements. Range expansion in B. hypnorum appears to depend, on exploitation of widespread habitats underutilised by native Bombus species, suggesting B. hypnorum will readily co-exist with these species. These findings suggest that management could target bumblebee species with distinctive habitat requirements to help maintain pollination service