Cubic order for spatial 't Hooft loop in hot QCD

Spatial 't Hooft loops of strength k measure the qualitative change in the behaviour of electric colour flux in confined and deconfined phase of SU(N) gauge theory. They show an area law in the deconfined phase, known analytically to two loop order with a ``k-scaling'' law k(N-k). In this paper we compute the O(g^3) correction to the tension. It is due to neutral gluon fields that get their mass through interaction with the wall. The simple k-scaling is lost in cubic order. The generic problem of non-convexity shows up in this order. The result for large N is explicitely given.Comment: 5 pages, appears in the proceedings of SEWM200

Spatial 't Hooft loop to cubic order in hot QCD II

In this paper we provide an exact formula for the area law of the 't Hooft loop for any SU(N) gauge group to cubic order in hot gauge theory. The correction is very small for all temperatures above $T_c$, in stark contrast to the cubic correction to the pressure. The gradient approximation in a previous paper, only valid for large N, is in excellent agreement with the present, exact evalution. Comparison to lattice data is good. Casimir scaling is violated by a small amount not yet resolved by the precision of lattice data.Comment: 21 pages, 5 figures, submitted to Nucl. Phys. B. Minor changes mad

Domain Walls and Metastable Vacua in Hot Orientifold Field Theories

We consider "Orientifold field theories", namely SU(N) gauge theories with Dirac fermions in the two-index representation at high temperature. When N is even these theories exhibit a spontaneously broken Z2 centre symmetry. We study aspects of the domain wall that interpolates between the two vacua of the theory. In particular we calculate its tension to two-loop order. We compare its tension to the corresponding domain wall in a SU(N) gauge theory with adjoint fermions and find an agreement at large-N, as expected from planar equivalence between the two theories. Moreover, we provide a non-perturbative proof for the coincidence of the tensions at large-N. We also discuss the vacuum structure of the theory when the fermion is given a large mass and argue that there exist N-2 metastable vacua. We calculate the lifetime of those vacua in the thin wall approximation.Comment: 29 pages, 4 figures. v2: minor changes in the introduction section. to appear in JHE

A Planck-scale axion and SU(2) Yang-Mills dynamics: Present acceleration and the fate of the photon

From the time of CMB decoupling onwards we investigate cosmological evolution subject to a strongly interacting SU(2) gauge theory of Yang-Mills scale $\Lambda\sim 10^{-4}$ eV (masquerading as the $U(1)_{Y}$ factor of the SM at present). The viability of this postulate is discussed in view of cosmological and (astro)particle physics bounds. The gauge theory is coupled to a spatially homogeneous and ultra-light (Planck-scale) axion field. As first pointed out by Frieman et al., such an axion is a viable candidate for quintessence, i.e. dynamical dark energy, being associated with today's cosmological acceleration. A prediction of an upper limit $\Delta t_{m_\gamma=0}$ for the duration of the epoch stretching from the present to the point where the photon starts to be Meissner massive is obtained: $\Delta t_{m_\gamma=0}\sim 2.2$ billion years.Comment: v3: consequences of an error in evolution equation for coupling rectified, only a minimal change in physics results, two refs. adde

Properties of the deconfining phase transition in SU(N) gauge theories

We extend our earlier investigation of the finite temperature deconfinement transition in SU(N) gauge theories, with the emphasis on what happens as N->oo. We calculate the latent heat in the continuum limit, and find the expected quadratic in N behaviour at large N. We confirm that the phase transition, which is second order for SU(2) and weakly first order for SU(3), becomes robustly first order for N>3 and strengthens as N increases. As an aside, we explain why the SU(2) specific heat shows no sign of any peak as T is varied across what is supposedly a second order phase transition. We calculate the effective string tension and electric gluon masses at T=Tc confirming the discontinuous nature of the transition for N>2. We explicitly show that the large-N `spatial' string tension does not vary with T for T<Tc and that it is discontinuous at T=Tc. For T>Tc it increases as T-squared to a good approximation, and the k-string tension ratios closely satisfy Casimir Scaling. Within very small errors, we find a single Tc at which all the k-strings deconfine, i.e. a step-by-step breaking of the relevant centre symmetry does not occur. We calculate the interface tension but are unable to distinguish between linear or quadratic in N variations, each of which can lead to a striking but different N=oo deconfinement scenario. We remark on the location of the bulk phase transition, which bounds the range of our large-N calculations on the strong coupling side, and within whose hysteresis some of our larger-N calculations are performed.Comment: 50 pages, 14 figure

Base-editing-mediated dissection of a γ-globin cis-regulatory element for the therapeutic reactivation of fetal hemoglobin expression

: Sickle cell disease and β-thalassemia affect the production of the adult β-hemoglobin chain. The clinical severity is lessened by mutations that cause fetal γ-globin expression in adult life (i.e., the hereditary persistence of fetal hemoglobin). Mutations clustering ~200 nucleotides upstream of the HBG transcriptional start sites either reduce binding of the LRF repressor or recruit the KLF1 activator. Here, we use base editing to generate a variety of mutations in the -200 region of the HBG promoters, including potent combinations of four to eight γ-globin-inducing mutations. Editing of patient hematopoietic stem/progenitor cells is safe, leads to fetal hemoglobin reactivation and rescues the pathological phenotype. Creation of a KLF1 activator binding site is the most potent strategy - even in long-term repopulating hematopoietic stem/progenitor cells. Compared with a Cas9-nuclease approach, base editing avoids the generation of insertions, deletions and large genomic rearrangements and results in higher γ-globin levels. Our results demonstrate that base editing of HBG promoters is a safe, universal strategy for treating β-hemoglobinopathies

Selective inhibition of the human tie-1 promoter with triplex-forming oligonucleotides targeted to ets binding sites

The Tie receptors (Tie-1 and Tie-2/Tek) are essential for angiogenesis and vascular remodeling/integrity. Tie receptors are up-regulated in tumor-associated endothelium, and their inhibition disrupts angiogenesis and can prevent tumor growth as a consequence. To investigate the potential of anti-gene approaches to inhibit tie gene expression for anti-angiogenic therapy, we have examined triple-helical (triplex) DNA formation at 2 tandem Ets transcription factor binding motifs (designated E-1 and E-2) in the human tie-1 promoter. Various tie-1 promoter deletion/mutation luciferase reporter constructs were generated and transfected into endothelial cells to examine the relative activities of E-1 and E-2. The binding of antiparallel and parallel (control) purine motif oligonucleotides (21-22 bp) targeted to E-1 and E-2 was assessed by plasmid DNA fragment binding and electrophoretic mobility shift assays. Triplex-forming oligonucleotides were incubated with tie-1 reporter constructs and transfected into endothelial cells to determine their activity. The Ets binding motifs in the E-1 sequence were essential for human tie-1 promoter activity in endothelial cells, whereas the deletion of E-2 had no effect. Antiparallel purine motif oligonucleotides targeted at E-1 or E-2 selectively formed strong triplex DNA (K(d) approximately 10(-7) M) at 37 degrees C. Transfection of tie-1 reporter constructs with triplex DNA at E-1, but not E-2, specifically inhibited tie-1 promoter activity by up to 75% compared with control oligonucleotides in endothelial cells. As similar multiple Ets binding sites are important for the regulation of several endothelial-restricted genes, this approach may have broad therapeutic potential for cancer and other pathologies involving endothelial proliferation/dysfunction