Opioid regulation of Mu receptor internalisation: relevance to the development of tolerance and dependence

Internalisation of the mu opioid receptor from the surface of cells is generally achieved by receptor occupancy with agonist ligands of high efficacy. However, in many situations the potent analgesic morphine fails to promote internalisation effectively and whether there is a direct link between this and the propensity for the sustained use of morphine to result in both tolerance and dependence has been studied intensely. Although frequently described as a partial agonist, this characteristic appears insufficient to explain the poor capacity of morphine to promote internalisation of the mu opioid receptor. Experiments performed using both transfected cell systems and ex vivo/in vivo models have provided evidence that when morphine can promote internalisation of the mu receptor there is a decrease in the development of tolerance and dependence. Although aspects of this model are controversial, such observations suggest a number of approaches to further enhance the use of morphine as an analgesic

NNLO Unquenched Calculation of the b Quark Mass

By combining the first unquenched lattice computation of the B-meson binding energy and the two-loop contribution to the lattice HQET residual mass, we determine the (\bar{{MS}}) (b)-quark mass, (\bar{m}_{b}(\bar{m}_{b})). The inclusion of the two-loop corrections is essential to extract (\bar{m}_{b}(\bar{m}_{b})) with a precision of ({\cal O}(\Lambda^{2}_{QCD}/m_{b})), which is the uncertainty due to the renormalon singularities in the perturbative series of the residual mass. Our best estimate is (\bar{m}_{b}(\bar{m}_{b}) = (4.26 \pm 0.09) {\rm GeV}), where we have combined the different errors in quadrature. A detailed discussion of the systematic errors contributing to the final number is presented. Our results have been obtained on a sample of (60) lattices of size (24^{3}\times 40) at (\beta =5.6), using the Wilson action for light quarks and the lattice HQET for the (b) quark, at two values of the sea quark masses. The quark propagators have been computed using the unquenched links generated by the T(\chi)L Collaboration.Comment: 19 pages, 1 figur

Combined Relativistic and static analysis for all Delta B=2 operators

We analyse matrix elements of Delta B=2 operators by combining QCD results with the ones obtained in the static limit of HQET. The matching of all the QCD operators to HQET is made at NLO order. To do that we have to include the anomalous dimension matrix up to two loops, both in QCD and HQET, and the one loop matching for all the Delta B=2 operators. The matrix elements of these operators are relevant for the prediction of the B-\bar B mixing, B_s meson width difference and supersymmetric effects in Delta B=2 transitions.Comment: 3 pages, 1 figure. Lattice2001(heavyquark

A Theoretical Prediction of the Bs-Meson Lifetime Difference

We present the results of a quenched lattice calculation of the operator matrix elements relevant for predicting the Bs width difference. Our main result is (\Delta\Gamma_Bs/\Gamma_Bs)= (4.7 +/- 1.5 +/- 1.6) 10^(-2), obtained from the ratio of matrix elements, R(m_b)=/<\bar B_s^0|Q_L|B_s^0>=-0.93(3)^(+0.00)_(-0.01). R(m_b) was evaluated from the two relevant B-parameters, B_S^{MSbar}(m_b)=0.86(2)^(+0.02)_(-0.03) and B_Bs^{MSbar}(m_b) = 0.91(3)^(+0.00)_(-0.06), which we computed in our simulation.Comment: 21 pages, 7 PostScript figure

Non-perturbative Renormalization of the Complete Basis of Four-fermion Operators and B-parameters

We present results on the B-parameters $B_K$, $B^{3/2}_7$ and $B^{3/2}_8$, at $\beta=6.0$, with the tree-level Clover action. The renormalization of the complete basis of dimension-six four-fermion operators has been performed non-perturbatively. Our results for $B_K$ and $B^{3/2}_7$ are in reasonable agreement with those obtained with the (unimproved) Wilson action. This is not the case for $B^{3/2}_8$. We also discuss some subtleties arising from a recently proposed modified definition of the B-parameters.Comment: Talk presented at Lattice '97, Edinburgh (UK), July 1997. LaTeX 3 pages, uses espcrc

A review of aceclofenac: Analgesic and anti-inflammatory effects on musculoskeletal disorders

Aceclofenac is an oral non-steroidal anti-inflammatory drug (NSAID) with antiinflammatory and analgesic properties. Although there are some differences in the authorized indications between countries, aceclofenac is mainly recommended for the treatment of inflammatory and painful processes, such as low back pain (LBP), scapulohumeral periarthritis, extraarticular rheumatism, odontalgia, and osteoarthritis (OA), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). The analgesic properties and tolerability profile of aceclofenac in musculoskeletal disorders are reviewed, focusing on relevant and recent studies. The efficacy and safety comparison of aceclofenac with other analgesics and anti-inflammatory agents in OA, AS, RA, and LBP is described. Relevant studies were identified following a literature search of PubMed using the terms “aceclofenac” and “clinical trials” published from 1 Jan 1992 to 1 Jan 2020. Aceclofenac is at least as effective as other NSAIDs in reducing pain and/or improving functional capacity in chronic pain conditions (OA, AS, RA, and LBP). It is generally well tolerated and appears to have a more favorable GI profile than other NSAIDs. Thus, current evidence indicates that aceclofenac is a useful option for the management of pain and inflammation across a wide range of painful conditions

K^0-\bar{K}^0 Mixing Beyond the SM from Nf=2 tmQCD

We present preliminary results on the of neutral kaon oscillations in extensions of the Standard Model. Using Nf=2 maximally twisted sea quarks and Osterwalder-Seiler valence quarks, we achieve both O(a)-improvement and continuum-like renormalization pattern for the relevant four-fermion operators. We perform simulations at three values of the lattice spacing and extrapolate/interpolate our results to the continuum limit and physical light/strange quark mass. The calculation of the renormalization constants of the complete operator basis is performed non- perturbatively in the RI-MOM scheme.Comment: 7 pages, 2 figures; presented at the XXVIII International Symposium on Lattice Field Theory Villasimius, Sardinia, Ital

Depth of interaction and bias voltage depenence of the spectral response in a pixellated CdTe detector operating in time-over-threshold mode subjected to monochromatic X-rays

High stopping power is one of the most important figures of merit for X-ray detectors. CdTe is a promising material but suffers from: material defects, non-ideal charge transport and long range X-ray fluorescence. Those factors reduce the image quality and deteriorate spectral information. In this project we used a monochromatic pencil beam collimated through a 20μm pinhole to measure the detector spectral response in dependance on the depth of interaction. The sensor was a 1mm thick CdTe detector with a pixel pitch of 110μm, bump bonded to a Timepix readout chip operating in Time-Over-Threshold mode. The measurements were carried out at the Extreme Conditions beamline I15 of the Diamond Light Source. The beam was entering the sensor at an angle of \texttildelow20 degrees to the surface and then passed through \texttildelow25 pixels before leaving through the bottom of the sensor. The photon energy was tuned to 77keV giving a variation in the beam intensity of about three orders of magnitude along the beam path. Spectra in Time-over-Threshold (ToT) mode were recorded showing each individual interaction. The bias voltage was varied between -30V and -300V to investigate how the electric field affected the spectral information. For this setup it is worth noticing the large impact of fluorescence. At -300V the photo peak and escape peak are of similar height. For high bias voltages the spectra remains clear throughout the whole depth but for lower voltages as -50V, only the bottom part of the sensor carries spectral information. This is an effect of the low hole mobility and the longer range the electrons have to travel in a low field