Background independent quantization and wave propagation

We apply a type of background independent "polymer" quantization to a free scalar field in a flat spacetime. Using semi-classical states, we find an effective wave equation that is both nonlinear and Lorentz invariance violating. We solve this equation perturbatively for several cases of physical interest, and show that polymer corrections to solutions of the Klein-Gordon equation depend on the amplitude of the field. This leads to an effective dispersion relation that depends on the amplitude, frequency and shape of the wave-packet, and is hence distinct from other modified dispersion relations found in the literature. We also demonstrate that polymer effects tend to accumulate with time for plane-symmetric waveforms. We conclude by discussing the possibility of measuring deviations from the Klein-Gordon equation in particle accelerators or astrophysical observations.Comment: 15 pages, minor revision to match PRD versio

Genericness of inflation in isotropic loop quantum cosmology

Non-perturbative corrections from loop quantum cosmology (LQC) to the scalar matter sector is already known to imply inflation. We prove that the LQC modified scalar field generates exponential inflation in the small scale factor regime, for all positive definite potentials, independent of initial conditions and independent of ambiguity parameters. For positive semi-definite potentials it is always possible to choose, without fine tuning, a value of one of the ambiguity parameters such that exponential inflation results, provided zeros of the potential are approached at most as a power law in the scale factor. In conjunction with generic occurrence of bounce at small volumes, particle horizon is absent thus eliminating the horizon problem of the standard Big Bang model.Comment: 4 pages, revtex4, one figure. Only e-print archive numbers correctedi in the second version. Reference added in the 3rd version. Final version to appear in Phys. Rev. Lett. Explanations improve

Cosmological vector modes and quantum gravity effects

In contrast to scalar and tensor modes, vector modes of linear perturbations around an expanding Friedmann--Robertson--Walker universe decay. This makes them largely irrelevant for late time cosmology, assuming that all modes started out at a similar magnitude at some early stage. By now, however, bouncing models are frequently considered which exhibit a collapsing phase. Before this phase reaches a minimum size and re-expands, vector modes grow. Such modes are thus relevant for the bounce and may even signal the breakdown of perturbation theory if the growth is too strong. Here, a gauge invariant formulation of vector mode perturbations in Hamiltonian cosmology is presented. This lays out a framework for studying possible canonical quantum gravity effects, such as those of loop quantum gravity, at an effective level. As an explicit example, typical quantum corrections, namely those coming from inverse densitized triad components and holonomies, are shown to increase the growth rate of vector perturbations in the contracting phase, but only slightly. Effects at the bounce of the background geometry can, however, be much stronger.Comment: 20 page

Background independent quantization and the uncertainty principle

It is shown that polymer quantization leads to a modified uncertainty principle similar to that obtained from string theory and non-commutative geometry. When applied to quantum field theory on general background spacetimes, corrections to the uncertainty principle acquire a metric dependence. For Friedmann-Robertson-Walker cosmology this translates to a scale factor dependence which gives a large effect in the early universe.Comment: 6 page

Hubble operator in isotropic loop quantum cosmology

We present a construction of the Hubble operator for the spatially flat isotropic loop quantum cosmology. This operator is a Dirac observable on a subspace of the space of physical solutions. This subspace gets selected dynamically, requiring that its action be invariant on the physical solution space. As a simple illustrative application of the expectation value of the operator, we do find a generic phase of (super)inflation, a feature shown by Bojowald from the analysis of effective Friedmann equation of loop quantum cosmology.Comment: 20 pages, 3 eps figures, few comments and clarifications added to match with the published versio

On Energy Conditions and Stability in Effective Loop Quantum Cosmology

In isotropic loop quantum cosmology, non-perturbatively modified dynamics of a minimally coupled scalar field violates weak, strong and dominant energy conditions when they are stated in terms of equation of state parameter. The violation of strong energy condition helps to have non-singular evolution by evading singularity theorems thus leading to a generic inflationary phase. However, the violation of weak and dominant energy conditions raises concern, as in general relativity these conditions ensure causality of the system and stability of vacuum via Hawking-Ellis conservation theorem. It is shown here that the non-perturbatively modified kinetic term contributes negative pressure but positive energy density. This crucial feature leads to violation of energy conditions but ensures positivity of energy density, as scalar matter Hamiltonian remains bounded from below. It is also shown that the modified dynamics restricts group velocity for inhomogeneous modes to remain sub-luminal thus ensuring causal propagation across spatial distances.Comment: 29 pages, revtex4; few clarifications, references added, to appear in CQ

Novel Escape Mutants Suggest an Extensive TRIM5α Binding Site Spanning the Entire Outer Surface of the Murine Leukemia Virus Capsid Protein

After entry into target cells, retroviruses encounter the host restriction factors such as Fv1 and TRIM5α. While it is clear that these factors target retrovirus capsid proteins (CA), recognition remains poorly defined in the absence of structural information. To better understand the binding interaction between TRIM5α and CA, we selected a panel of novel N-tropic murine leukaemia virus (N-MLV) escape mutants by a serial passage of replication competent N-MLV in rhesus macaque TRIM5α (rhTRIM5α)-positive cells using a small percentage of unrestricted cells to allow multiple rounds of virus replication. The newly identified mutations, many of which involve changes in charge, are distributed over the outer ‘top’ surface of N-MLV CA, including the N-terminal β-hairpin, and map up to 29 Ao apart. Biological characterisation with a number of restriction factors revealed that only one of the new mutations affects restriction by human TRIM5α, indicating significant differences in the binding interaction between N-MLV and the two TRIM5αs, whereas three of the mutations result in dual sensitivity to Fv1n and Fv1b. Structural studies of two mutants show that no major changes in the overall CA conformation are associated with escape from restriction. We conclude that interactions involving much, if not all, of the surface of CA are vital for TRIM5α binding

Assisted evolution enables HIV-1 to overcome a high trim5α-imposed genetic barrier to rhesus macaque tropism

Diversification of antiretroviral factors during host evolution has erected formidable barriers to cross-species retrovirus transmission. This phenomenon likely protects humans from infection by many modern retroviruses, but it has also impaired the development of primate models of HIV-1 infection. Indeed, rhesus macaques are resistant to HIV-1, in part due to restriction imposed by the TRIM5α protein (rhTRIM5α). Initially, we attempted to derive rhTRIM5α-resistant HIV-1 strains using two strategies. First, HIV-1 was passaged in engineered human cells expressing rhTRIM5α. Second, a library of randomly mutagenized capsid protein (CA) sequences was screened for mutations that reduced rhTRIM5α sensitivity. Both approaches identified several individual mutations in CA that reduced rhTRIM5α sensitivity. However, neither approach yielded mutants that were fully resistant, perhaps because the locations of the mutations suggested that TRIM5α recognizes multiple determinants on the capsid surface. Moreover, even though additive effects of various CA mutations on HIV-1 resistance to rhTRIM5α were observed, combinations that gave full resistance were highly detrimental to fitness. Therefore, we employed an 'assisted evolution' approach in which individual CA mutations that reduced rhTRIM5α sensitivity without fitness penalties were randomly assorted in a library of viral clones containing synthetic CA sequences. Subsequent passage of the viral library in rhTRIM5α-expressing cells resulted in the selection of individual viral species that were fully fit and resistant to rhTRIM5α. These viruses encoded combinations of five mutations in CA that conferred complete or near complete resistance to the disruptive effects of rhTRIM5α on incoming viral cores, by abolishing recognition of the viral capsid. Importantly, HIV-1 variants encoding these CA substitutions and SIVmac239 Vif replicated efficiently in primary rhesus macaque lymphocytes. These findings demonstrate that rhTRIM5α is difficult to but not impossible to evade, and doing so should facilitate the development of primate models of HIV-1 infection

Temperature-ramped 129Xe spin-exchange optical pumping

We describe temperature-ramped spin-exchange optical pumping (TR-SEOP) in an automated high-throughput batch-mode 129Xe hyperpolarizer utilizing three key temperature regimes: (i) “hot”where the 129Xe hyperpolarization rate is maximal, (ii) “warm”-where the 129Xe hyperpolarization approaches unity, and (iii) “cool” where hyperpolarized 129Xe gas is transferred into a Tedlar bag with low Rb content (<5 ng per ∼1 L dose) suitable for human imaging applications. Unlike with the conventional approach of batch-mode SEOP, here all three temperature regimes may be operated under continuous high-power (170 W) laser irradiation, and hyperpolarized 129Xe gas is delivered without the need for a cryocollection step. The variable-temperature approach increased the SEOP rate by more than 2-fold compared to the constant-temperature polarization rate (e.g., giving effective values for the exponential buildup constant γSEOP of 62.5 ± 3.7 × 10−3 min−1 vs 29.9 ± 1.2 × 10−3 min−1) while achieving nearly the same maximum %PXe value (88.0 ± 0.8% vs 90.1% ± 0.8%, for a 500 Torr (67 kPa) Xe cell loadingcorresponding to nuclear magnetic resonance/magnetic resonance imaging (NMR/MRI) enhancements of ∼3.1 × 105 and ∼2.32 × 108 at the relevant fields for clinical imaging and HP 129Xe production of 3 T and 4 mT, respectively); moreover, the intercycle “dead” time was also significantly decreased. The higher-throughput TR-SEOP approach can be implemented without sacrificing the level of 129Xe hyperpolarization or the experimental stability for automation-making this approach beneficial for improving the overall 129Xe production rate in clinical settings

Structure and non-structure of centrosomal proteins

Here we perform a large-scale study of the structural properties and the expression of proteins that constitute the human Centrosome. Centrosomal proteins tend to be larger than generic human proteins (control set), since their genes contain in average more exons (20.3 versus 14.6). They are rich in predicted disordered regions, which cover 57% of their length, compared to 39% in the general human proteome. They also contain several regions that are dually predicted to be disordered and coiled-coil at the same time: 55 proteins (15%) contain disordered and coiled-coil fragments that cover more than 20% of their length. Helices prevail over strands in regions homologous to known structures (47% predicted helical residues against 17% predicted as strands), and even more in the whole centrosomal proteome (52% against 7%), while for control human proteins 34.5% of the residues are predicted as helical and 12.8% are predicted as strands. This difference is mainly due to residues predicted as disordered and helical (30% in centrosomal and 9.4% in control proteins), which may correspond to alpha-helix forming molecular recognition features (α-MoRFs). We performed expression assays for 120 full-length centrosomal proteins and 72 domain constructs that we have predicted to be globular. These full-length proteins are often insoluble: Only 39 out of 120 expressed proteins (32%) and 19 out of 72 domains (26%) were soluble. We built or retrieved structural models for 277 out of 361 human proteins whose centrosomal localization has been experimentally verified. We could not find any suitable structural template with more than 20% sequence identity for 84 centrosomal proteins (23%), for which around 74% of the residues are predicted to be disordered or coiled-coils. The three-dimensional models that we built are available at http://ub.cbm.uam.es/centrosome/models/index.php