Status of center dominance in various center gauges

We review arguments for center dominance in center gauges where vortex locations are correctly identified. We introduce an appealing interpretation of the maximal center gauge, discuss problems with Gribov copies, and a cure to the problems through the direct Laplacian center gauge. We study correlations between direct and indirect Laplacian center gauges.Comment: Presented by S. Olejnik at the NATO Advanced Research Workshop "Confinement, Topology, and other Non-Perturbative Aspects of QCD", Jan. 21-27, 2002, Stara Lesna, Slovakia. 10 pages, 3 figures (8 EPS files), uses crckapb.st

The deconfinement transition of finite density QCD with heavy quarks from strong coupling series

Starting from Wilson's action, we calculate strong coupling series for the Polyakov loop susceptibility in lattice gauge theories for various small N_\tau in the thermodynamic limit. Analysing the series with Pad\'e approximants, we estimate critical couplings and exponents for the deconfinement phase transition. For SU(2) pure gauge theory our results agree with those from Monte-Carlo simulations within errors, which for the coarser N_\tau=1,2 lattices are at the percent level. For QCD we include dynamical fermions via a hopping parameter expansion. On a N_\tau=1 lattice with N_f=1,2,3, we locate the second order critical point where the deconfinement transition turns into a crossover. We furthermore determine the behaviour of the critical parameters with finite chemical potential and find the first order region to shrink with growing \mu. Our series moreover correctly reflects the known Z(N) transition at imaginary chemical potential.Comment: 18 pages, 7 figures, typos corrected, version published in JHE

Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release.

Human genetic studies show that the voltage gated sodium channel 1.7 (Nav1.7) is a key molecular determinant of pain sensation. However, defining the Nav1.7 contribution to nociceptive signalling has been hampered by a lack of selective inhibitors. Here we report two potent and selective arylsulfonamide Nav1.7 inhibitors; PF-05198007 and PF-05089771, which we have used to directly interrogate Nav1.7's role in nociceptor physiology. We report that Nav1.7 is the predominant functional TTX-sensitive Nav in mouse and human nociceptors and contributes to the initiation and the upstroke phase of the nociceptor action potential. Moreover, we confirm a role for Nav1.7 in influencing synaptic transmission in the dorsal horn of the spinal cord as well as peripheral neuropeptide release in the skin. These findings demonstrate multiple contributions of Nav1.7 to nociceptor signalling and shed new light on the relative functional contribution of this channel to peripheral and central noxious signal transmission.The funder provided support in the form of salaries for authors [AA, AB, MC, JT, MM, AW, EP, AG, PJC, RD, DP, ZL, BM, CW, NS, RS, PS, NC, DK, RB, ES], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The specific roles of these authors are articulated in the ‘author contributions’ section

Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia

In common with other chronic pain conditions, there is an unmet clinical need in the treatment of inherited erythromelalgia (IEM). TheSCN9Agene encoding the sodium channel Nav1.7 expressed in the peripheral nervous system plays a critical role in IEM. A gain-of-function mutation in this sodium channel leads to aberrant sensory neuronal activity and extreme pain, particularly in response to heat. Five patients with IEM were treated with a new potent and selective compound that blocked the Nav1.7 sodium channel resulting in a decrease in heat-induced pain in most of the patients. We derived induced pluripotent stem cell (iPSC) lines from four of five subjects and produced sensory neurons that emulated the clinical phenotype of hyperexcitability and aberrant responses to heat stimuli. When we compared the severity of the clinical phenotype with the hyperexcitability of the iPSC-derived sensory neurons, we saw a trend toward a correlation for individual mutations. The in vitro IEM phenotype was sensitive to Nav1.7 blockers, including the clinical test agent. Given the importance of peripherally expressed sodium channels in many pain conditions, our approach may have broader utility for a wide range of pain and sensory conditions

Bayesian molecular clock dating of species divergences in the genomics era

It has been five decades since the proposal of the molecular clock hypothesis, which states that the rate of evolution at the molecular level is constant through time and among species. This hypothesis has become a powerful tool in evolutionary biology, making it possible to use molecular sequences to estimate the geological ages of species divergence events. With recent advances in Bayesian clock dating methodology and the explosive accumulation of genetic sequence data, molecular clock dating has found widespread applications, from tracking virus pandemics, to studying the macroevolutionary process of speciation and extinction, to estimating a timescale for Life on Earth

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe