Effective string action for the U(1)xU(1) dual Ginzburg-Landau theory beyond the London limit

The effective string action of the color-electric flux tube in the U(1) x U(1) dual Ginzburg-Landau (DGL) theory is studied by performing a path-integral analysis by taking into accountthe finite thickness of the flux tube. The DGL theory, corresponding to the low-energy effective theory of Abelian-projected SU(3) gluodynamics, can be expressed as s [U(1)]^{3} dual Abelian Higgs (DAH) model with a certain constraint in the Weyl symmetric formulation. This formulation allows us to adopt quite similar path-integral techniques as in the U(1) DAH model, and therefore, the resulting effective string action in the U(1) x U(1) DGL theory has also quite a similar structure except the number of color degrees of freedom. A modified Yukawa interaction appears as a boundary contribution, which is completely due to the finite thickness of the flux tube, and is reduced into the ordinary Yukawa interaction in the deep type-II (London) Limit.Comment: 17 pages, 1 eps figure, The version accepted for publication in Nucl. Phys.

On the density matrix for the kink ground state of higher spin XXZ chain

The exact expression for the density matrix of the kink ground state of higher spin XXZ chain is obtained

Analysis of Adaptive Mutations in HIV-1 Env-gp120

HIV-1 Env protein functions in the entry process and is the target of neutralizing antibodies. Its intrinsically high mutation rate is certainly one of driving forces for persistence/survival in hosts. For optimal replication in various environments, HIV-1 Env must continue to adapt and evolve through balancing sometimes incompatible function, replication fitness, and neutralization sensitivity. We have previously reported that adapted viruses emerge in repeated and prolonged cultures of cells originally infected with a macaque-tropic HIV-1NL4-3 derivative. We have also shown that the adapted viral clones exhibit enhanced growth potentials both in macaque PBMCs and individuals, and that three single-amino acid mutations are present in their Env V1/C2/C4 domains. In this study, we investigated how lab-adapted and highly neutralization-sensitive HIV-1NL4-3 adapts its Env to macaque cells with strongly replication-restrictive nature for HIV-1. While a single and two mutations gave a significantly enhanced replication phenotype in a macaque cell line and also in human cell lines that stably express either human CD4 or macaque CD4, the virus simultaneously carrying the three adaptive mutations always grew best. Entry kinetics of parental and triple mutant viruses were similar, whereas the mutant was significantly more readily inhibited for its infectivity by soluble CD4 than parental virus. Furthermore, molecular dynamics simulations of the Env ectodomain (gp120 and gp41 ectodomain) bound with CD4 suggest that the three mutations increase binding affinity of Env for CD4 in solution. Thus, it is quite likely that the affinity for CD4 of the mutant Env is enhanced relative to the parental Env. Neutralization sensitivity of the triple mutant to CD4 binding site antibodies was not significantly different from that of parental virus, whereas the mutant exhibited a considerably higher resistance against neutralization by a CD4-induced epitope antibody and Env trimer-targeting V1/V2 antibodies. These results suggest that the three adaptive mutations cooperatively promote viral growth via increased CD4 affinity, and also that they enhance viral resistance to several neutralization antibodies by changing the Env-trimer conformation. In total, we have verified here an HIV-1 adaptation pathway in host cells and individuals involving Env derived from a lab-adapted and highly neutralization-sensitive clone

Updating kriging surrogate models based on the hypervolume indicator in multi-objective optimization

This paper presents a comparison of the criteria for updating the Kriging surrogate models in multi-objective optimization: expected improvement (EI), expected hypervolume improvement (EHVI), estimation (EST), and those in combination (EHVI þ EST). EI has been conventionally used as the criterion considering the stochastic improvement of each objective function value individually, while EHVI has recently been proposed as the criterion considering the stochastic improvement of the front of nondominated solutions in multi-objective optimization. EST is the value of each objective function estimated nonstochastically by the Kriging model without considering its uncertainties. Numerical experiments were implemented in the welded beam design problem, and empirically showed that, in an unconstrained case, EHVI maintains a balance between accuracy, spread, and uniformity in nondominated solutions for Krigingmodel-based multiobjective optimization. In addition, the present experiments suggested future investigation into techniques for handling constraints with uncertainties to enhance the capability of EHVI in constrained cases

Modulation of vif-mRNA by HIV-1-SA1D2prox

Genomic RNA of HIV-1 contains localized structures critical for viral replication. Its structural analysis has demonstrated a stem-loop structure, SLSA1, in a nearby region of HIV-1 genomic splicing acceptor 1 (SA1). We have previously shown that the expression level of vif mRNA is considerably altered by some natural single-nucleotide variations (nSNVs) clustering in SLSA1 structure. In this study, besides eleven nSNVs previously identified by us, we totally found nine new nSNVs in the SLSA1-containing sequence from SA1, splicing donor 2, and through to the start codon of Vif that significantly affect the vif mRNA level, and designated the sequence SA1D2prox (142 nucleotides for HIV-1 NL4-3). We then examined by extensive variant and mutagenesis analyses how SA1D2prox sequence and SLSA1 secondary structure are related to vif mRNA level. While the secondary structure and stability of SLSA1 was largely changed by nSNVs and artificial mutations introduced to restore the original NL4-3 form from altered ones by nSNVs, no clear association of the two SLSA1 properties with vif mRNA level was observed. In contrast, when naturally occurring SA1D2prox sequences that contain multiple nSNVs were examined, we attained significant inverse correlation between the vif level and SLSA1 stability. These results may suggest that SA1D2prox sequence adapts over time, and also that the altered SA1D2prox sequence, SLSA1 stability, and vif level are mutually related. In total, we show here that the entire SA1D2prox sequence and SLSA1 stability critically contribute to the modulation of vif mRNA level

V3 Tip-Dependent Species Specificity of HIV-1 Env

Molecular interactions of the variable envelope gp120 subunit of HIV-1 with two cellular receptors are the first step of viral infection, thereby playing pivotal roles in determining viral infectivity and cell tropism. However, the underlying regulatory mechanisms for interactions under gp120 spontaneous variations largely remain unknown. Here, we show an allosteric mechanism in which a single gp120 mutation remotely controls the ternary interactions between gp120 and its receptors for the switch of viral cell tropism. Virological analyses showed that a G310R substitution at the tip of the gp120 V3 loop selectively abolished the viral replication ability in human cells, despite evoking enhancement of viral replication in macaque cells. Molecular dynamics (MD) simulations predicted that the G310R substitution at a site away from the CD4 interaction site selectively impeded the binding ability of gp120 to human CD4. Consistently, virions with the G310R substitution exhibited a reduced binding ability to human lymphocyte cells. Furthermore, the G310R substitution influenced the gp120-CCR5 interaction in a CCR5-type dependent manner as assessed by MD simulations and an infectivity assay using exogenously expressed CCR5s. Interestingly, an I198M mutation in human CCR5 restored the infectivity of the G310R virus in human cells. Finally, MD simulation predicted amino acid interplays that physically connect the V3 loop and gp120 elements for the CD4 and CCR5 interactions. Collectively, these results suggest that the V3 loop tip is a cis-allosteric regulator that remotely controls intra- and intermolecular interactions of HIV-1 gp120 for balancing ternary interactions with CD4 and CCR5

Concomitant Enhancement of HIV-1 Replication Potential and Neutralization-Resistance in Concert With Three Adaptive Mutations in Env V1/C2/C4 Domains

HIV-1 Env protein functions in the entry process and is the target of neutralizing antibodies. Its intrinsically high mutation rate is certainly one of driving forces for persistence/survival in hosts. For optimal replication in various environments, HIV-1 Env must continue to adapt and evolve through balancing sometimes incompatible function, replication fitness, and neutralization sensitivity. We have previously reported that adapted viruses emerge in repeated and prolonged cultures of cells originally infected with a macaque-tropic HIV-1NL4-3 derivative. We have also shown that the adapted viral clones exhibit enhanced growth potentials both in macaque PBMCs and individuals, and that three single-amino acid mutations are present in their Env V1/C2/C4 domains. In this study, we investigated how lab-adapted and highly neutralization-sensitive HIV-1NL4-3 adapts its Env to macaque cells with strongly replication-restrictive nature for HIV-1. While a single and two mutations gave a significantly enhanced replication phenotype in a macaque cell line and also in human cell lines that stably express either human CD4 or macaque CD4, the virus simultaneously carrying the three adaptive mutations always grew best. Entry kinetics of parental and triple mutant viruses were similar, whereas the mutant was significantly more readily inhibited for its infectivity by soluble CD4 than parental virus. Furthermore, molecular dynamics simulations of the Env ectodomain (gp120 and gp41 ectodomain) bound with CD4 suggest that the three mutations increase binding affinity of Env for CD4 in solution. Thus, it is quite likely that the affinity for CD4 of the mutant Env is enhanced relative to the parental Env. Neutralization sensitivity of the triple mutant to CD4 binding site antibodies was not significantly different from that of parental virus, whereas the mutant exhibited a considerably higher resistance against neutralization by a CD4-induced epitope antibody and Env trimer-targeting V1/V2 antibodies. These results suggest that the three adaptive mutations cooperatively promote viral growth via increased CD4 affinity, and also that they enhance viral resistance to several neutralization antibodies by changing the Env-trimer conformation. In total, we have verified here an HIV-1 adaptation pathway in host cells and individuals involving Env derived from a lab-adapted and highly neutralization-sensitive clone

Low-lying spectrum of the Y-string three-quark potential using hyper-spherical coordinates

We calculate the energies of three-quark states with definite permutation symmetry (i.e. of SU(6) multiplets) in the N=0,1,2 shells, confined by the Y-string three-quark potential. The exact Y-string potential consists of one, so-called three-string term, and three angle-dependent two-string terms. Due to this technical complication we treat the problem at three increasingly accurate levels of approximation: 1) the (approximate) three-string potential expanded to first order in trigonometric functions of hyper-spherical angles; 2) the (approximate) three-string potential to all orders in the power expansion in hyper-spherical harmonics, but without taking into account the transition(s) to two-string potentials; 3) the exact minimal-length string potential to all orders in power expansion in hyper-spherical harmonics, and taking into account the transition(s) to two-string potentials. We show the general trend of improvement %convergence of these approximations: The exact non-perturbative corrections to the total energy are of the order of one per cent, as compared with approximation 2), yet the exact energy differences between the $[20,1^{+}], [70,2^{+}], [56,2^{+}], [70,0^{+}]$-plets are shifted to 2:2:0.9, from the Bowler and Tynemouth separation rule 2:2:1, which is obeyed by approximation 2) at the one per cent level. The precise value of the energy separation of the first radial excitation ("Roper") $[56^{\prime},0^{+}]$-plet from the $[70,1^{-}]$-plet depends on the approximation, but does not become negative, i.e. the "Roper" remains heavier than the odd-parity $[70,1^{-}]$-plet in all of our approximations.Comment: 19 pages, 6 figure

Constitutive, but Not Challenge-Induced, Interleukin-10 Production Is Robust in Acute Pre-Pubescent Protein and Energy Deficits: New Support for the Tolerance Hypothesis of Malnutrition-Associated Immune Depression Based on Cytokine Production in vivo

The tolerance model of acute (i.e., wasting) pre-pubescent protein and energy deficits proposes that the immune depression characteristic of these pathologies reflects an intact anti-inflammatory form of immune competence that reduces the risk of autoimmune reactions to catabolically released self antigens. A cornerstone of this proposition is the finding that constitutive (first-tier) interleukin(IL)-10 production is sustained even into the advanced stages of acute malnutrition. The IL-10 response to inflammatory challenge constitutes a second tier of anti-inflammatory regulation and was the focus of this investigation. Weanling mice consumed a complete diet ad libitum, a low-protein diet ad libitum (mimicking incipient kwashiorkor), or the complete diet in restricted daily quantities (mimicking marasmus), and their second-tier IL-10 production was determined both in vitro and in vivo using lipopolysaccharide (LPS) and anti-CD3 as stimulants of innate and adaptive defences, respectively. Both early (3 days) and advanced (14 days) stages of wasting pathology were examined and three main outcomes emerged. First, classic in vitro systems are unreliable for discerning cytokine production in vivo. Secondly, in diverse forms of acute malnutrition declining challenge-induced IL-10 production may provide an early sign that anti-inflammatory control over immune competence is failing. Thirdly, and most fundamentally, the investigation provides new support for the tolerance model of malnutrition-associated inflammatory immune depression

Flux-Tube Ring and Glueball Properties in the Dual Ginzburg-Landau Theory

An intuitive approach to the glueball using the flux-tube ring solution in the dual Ginzburg-Landau theory is presented. The description of the flux-tube ring as the relativistic closed string with the effective string tension enables us to write the hamiltonian of the flux-tube ring using the Nambu-Goto action. Analyzing the Schr\"odinger equation, we discuss the mass spectrum and the wave function of the glueball. The lowest glueball state is found to have the mass $M_G \sim 1.6 GeV$ and the size $R_G \sim 0.5 fm$.Comment: 24 pages, 6 figures, revte