Current and Future Issues in the Development of Spinal Agents for the Management of Pain.

Targeting analgesic drugs for spinal delivery reflects the fact that while the conscious experience of pain is mediated supraspinally, input initiated by high intensity stimuli, tissue injury and/or nerve injury is encoded at the level of the spinal dorsal horn and this output informs the brain as to the peripheral environment. This encoding process is subject to strong upregulation resulting in hyperesthetic states and downregulation reducing the ongoing processing of nociceptive stimuli reversing the hyperesthesia and pain processing. The present review addresses the biology of spinal nociceptive processing as relevant to the effects of intrathecally-delivered drugs in altering pain processing following acute stimulation, tissue inflammation/injury and nerve injury. The review covers i) the major classes of spinal agents currently employed as intrathecal analgesics (opioid agonists, alpha 2 agonists; sodium channel blockers; calcium channel blockers; NMDA blockers; GABA A/B agonists; COX inhibitors; ii) ongoing developments in the pharmacology of spinal therapeutics focusing on less studied agents/targets (cholinesterase inhibition; Adenosine agonists; iii) novel intrathecal targeting methodologies including gene-based approaches (viral vectors, plasmids, interfering RNAs); antisense, and toxins (botulinum toxins; resniferatoxin, substance P Saporin); and iv) issues relevant to intrathecal drug delivery (neuraxial drug distribution), infusate delivery profile, drug dosing, formulation and principals involved in the preclinical evaluation of intrathecal drug safety

The role of cell-cell adhesion in wound healing

We present a stochastic model which describes fronts of cells invading a wound. In the model cells can move, proliferate, and experience cell-cell adhesion. We find several qualitatively different regimes of front motion and analyze the transitions between them. Above a critical value of adhesion and for small proliferation large isolated clusters are formed ahead of the front. This is mapped onto the well-known ferromagnetic phase transition in the Ising model. For large adhesion, and larger proliferation the clusters become connected (at some fixed time). For adhesion below the critical value the results are similar to our previous work which neglected adhesion. The results are compared with experiments, and possible directions of future work are proposed.Comment: to appear in Journal of Statistical Physic

Selection of ULIRGs in Infrared and Submm Surveys

We examine the selection characteristics of infrared and sub-mm surveys with IRAS, Spitzer, BLAST, Herschel and SCUBA and identify the range of dust temperatures these surveys are sensitive to, for galaxies in the ULIRG luminosity range (12<log(LIR)<13), between z=0 and z=4. We find that the extent of the redshift range over which surveys are unbiased is a function of the wavelength of selection, flux density limit and ULIRG luminosity. Short wavelength (<200{\mu}m) surveys with IRAS, Spitzer/MIPS and Herschel/PACS are sensitive to all SED types in a large temperature interval (17-87K), over a substantial fraction of their accessible redshift range. On the other hand, long wavelength (>200{\mu}m) surveys with BLAST, Herschel/ SPIRE and SCUBA are significantly more sensitive to cold ULIRGs, disfavouring warmer SEDs even at low redshifts. We evaluate observations in the context of survey selection effects, finding that the lack of cold ULIRGs in the local (z<0.1) Universe is not a consequence of selection and that the range of ULIRG temperatures seen locally is only a subset of a much larger range which exists at high redshift. We demonstrate that the local luminosity-temperature (L-T) relation, which indicates that more luminous sources are also hotter, is not applicable in the distant Universe when extrapolated to the ULIRG regime, because the scatter in observed temperatures is too large. Finally, we show that the difference between the ULIRG temperature distributions locally and at high redshift is not the result of galaxies becoming colder due to an L-T relation which evolves as a function of redshift. Instead, they are consistent with a picture where the evolution of the infrared luminosity function is temperature dependent, i.e. cold galaxies evolve at a faster rate than their warm counterparts.Comment: 11 pages, 6 figures, accepted for publication in MNRA

Quantum Mott Transition and Multi-Furcating Criticality

Phenomenological theory of the Mott transition is presented. When the critical temperature of the Mott transition is much higher than the quantum degeneracy temperature, the transition is essentially described by the Ising universality class. Below the critical temperature, phase separation or first-order transition occurs. However, if the critical point is involved in the Fermi degeneracy region, a marginal quantum critical point appears at zero temperature. The originally single Mott critical point generates subsequent many unstable fixed points through various Fermi surface instabilities induced by the Mott criticality characterized by the diverging charge susceptibility or doublon susceptibility. This occurs in marginal quantum-critical region. Charge, magnetic and superconducting instabilitites compete severely under these critical charge fluctuations. The quantum Mott transition triggers multi-furcating criticality, which goes beyond the conventional concept of multicriticality in quantum phase transitions. Near the quantum Mott transition, the criticality generically drives growth of inhomogeneous structure in the momentum space with singular points of flat dispersion on the Fermi surface. The singular points determine the quantum dynamics of the Mott transition by the dynamical exponent $z=4$. We argue that many of filling-control Mott transitions are classified to this category. Recent numerical results as well as experimental results on strongly correlated systems including transition metal oxides, organic materials and $^3$He layer adsorbed on a substrate are consistently analyzed especially in two-dimensional systems.Comment: 28 pages including 2 figure

Improved Measurement of the Partial-Rate CP Asymmetry in B+ -> K0pi+ and B- -> K0bar pi- Decays

We report an improved measurement of the partial-rate CP asymmetry in B+ => K0pi+ and B- => K0bar pi- decays. The analysis is based on a data sample of 85 million BBbar pairs collected at the Upsilon(4S) resonance with the Belle detector at the KEKB e+ e- storage ring. We measure Acp(K0pi+-) = 0.07^{+0.09 +0.01}_{-0.08 -0.03}, where the first and second errors are statistical and systematic, respectively; the corresponding 90% confidence-level interval is -0.10 < Acp(K0pi+-) < 0.22 .Comment: 7 pages, 8 figures, submitted to Phys. Rev.

Improved Measurements of Branching Fractions for B->Kpi, pipi and KK Decays

We report improved measurements of branching fractions for $B\to K\pi$, $\pi^+\pi^-$, $\pi^+\pi^0$ and $K\bar{K}$ decays based on a data sample of 85.0 million $B\bar{B}$ pairs collected at the $\Upsilon (4S)$ resonance with the Belle detector at the KEKB $e^+e^-$ storage ring. This data sample is almost three times larger than the sample previously used. We observe clear signals for $B\to K\pi$, $\pi^+\pi^-$ and $\pi^+\pi^0$ decays and set upper limits on $B\to K\bar{K}$ decays. The results can be used to give model-dependent constraints on the CKM angle $\phi_3$, as well as limits on the hadronic uncertainty in the time-dependent analysis of the angle $\phi_2$.Comment: 10 pages, 1 figure, 4 tables. Submitted to Phys. Rev. D Rapid Communications. Several corrections were mad

Study of B meson decays to three-body charmless hadronic final states

We report results of a study of charmless B meson decays to three-body KPiPi, KKPi and KKK final states. Measurements of branching fractions for B decays to K+0Pi+Pi-, K+K+K-, K0K+K-, KsKsK+ and KsKsKs final states are presented. The decays B0=>K0K+K-, B+=>KsKsK+ and B0=>KsKsKs are observed for the first time. We also report evidence for B+=>K+K-Pi+ decay. For the three-body final states K0K+K-, KsKsPi+, K+K+Pi- and K-Pi+Pi+ 90% confidence level upper limits are reported. Finally, we discuss the possibility of using the three-body B0=>KsK+K- decay for CP violation studies. The results are obtained with a 78 fb^-1 data sample collected at the Y(4S) resonance by the Belle detector operating at the KEKB asymmetric energy e+e- collider.Comment: 15 pages, 6 figures. To be submitted to PR

Measurement of Semileptonic Branching Fractions of B Mesons to Narrow D** States

Using the data accumulated in 2002-2004 with the DO detector in proton-antiproton collisions at the Fermilab Tevatron collider with centre-of-mass energy 1.96 TeV, the branching fractions of the decays B -> \bar{D}_1^0(2420) \mu^+ \nu_\mu X and B -> \bar{D}_2^{*0}(2460) \mu^+ \nu_\mu X and their ratio have been measured: BR(\bar{b}->B) \cdot BR(B-> \bar{D}_1^0 \mu^+ \nu_\mu X) \cdot BR(\bar{D}_1^0 -> D*- pi+) = (0.087+-0.007(stat)+-0.014(syst))%; BR(\bar{b}->B)\cdot BR(B->D_2^{*0} \mu^+ \nu_\mu X) \cdot BR(\bar{D}_2^{*0} -> D*- \pi^+) = (0.035+-0.007(stat)+-0.008(syst))%; and (BR(B -> \bar{D}_2^{*0} \mu^+ \nu_\mu X)BR(D2*0->D*- pi+)) / (BR(B -> \bar{D}_1^{0} \mu^+ \nu_\mu X)\cdot BR(\bar{D}_1^{0}->D*- \pi^+)) = 0.39+-0.09(stat)+-0.12(syst), where the charge conjugated states are always implied.Comment: submitted to Phys. Rev. Let