Role of retroviral restriction factors in the interferon-α-mediated suppression of HIV-1 in vivo

The antiviral potency of the cytokine IFN-α has been long appreciated but remains poorly understood. A number of studies have suggested that induction of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3) and bone marrow stromal cell antigen 2 (BST-2/tetherin/CD317) retroviral restriction factors underlies the IFN-α-mediated suppression of HIV-1 replication in vitro. We sought to characterize the as-yet-undefined relationship between IFN-α treatment, retroviral restriction factors, and HIV-1 in vivo. APOBEC3G, APOBEC3F, and BST-2 expression levels were measured in HIV/hepatitis C virus (HCV)-coinfected, antiretroviral therapy-naïve individuals before, during, and after pegylated IFN-α/ribavirin (IFN-α/riba) combination therapy. IFN-α/riba therapy decreased HIV-1 viral load by -0.921 (±0.858) log(10) copies/mL in HIV/HCV-coinfected patients. APOBEC3G/3F and BST-2 mRNA expression was significantly elevated during IFN-α/riba treatment in patient-derived CD4+ T cells (P < 0.04 and P < 0.008, paired Wilcoxon), and extent of BST-2 induction was correlated with reduction in HIV-1 viral load during treatment (P < 0.05, Pearson's r). APOBEC3 induction during treatment was correlated with degree of viral hypermutation (P < 0.03, Spearman's ρ), and evolution of the HIV-1 accessory protein viral protein U (Vpu) during IFN-α/riba treatment was suggestive of increased BST-2-mediated selection pressure. These data suggest that host restriction factors play a critical role in the antiretroviral capacity of IFN-α in vivo, and warrant investigation into therapeutic strategies that specifically enhance the expression of these intrinsic immune factors in HIV-1-infected individuals.

Association of optical tracklets from a geosynchronous belt survey via the direct Bayesian admissible region approach

The direct Bayesian admissible region approach is an a priori state free measurement association and initial orbit determination technique for optical tracks. In this paper, we test a hybrid approach that appends a least squares estimator to the direct Bayesian method on measurements taken at the Zimmerwald Observatory of the Astronomical Institute at the University of Bern. Over half of the association pairs agreed with conventional geometric track correlation and least squares techniques. The remaining pairs cast light on the fundamental limits of conducting tracklet association based solely on dynamical and geometrical information.

A boundary value problem approach to too-short arc optical track association

Given a short-arc optical observation with estimated angle-rates, the admissible region is a compact region in the range / range-rate space defined such that all likely and relevant orbits are contained within it. An alternative boundary value problem formulation has recently been proposed where range / range hypotheses are generated with two angle measurements from two tracks as input. In this paper, angle-rate information is reintroduced as a means to eliminate hypotheses by bounding their constants of motion before a more computationally costly Lambert solver or differential correction algorithm is run.

Unfolding Feasible Arithmetic and Weak Truth

In this paper we continue Feferman’s unfolding program initiated in (Feferman, vol. 6 of Lecture Notes in Logic, 1996) which uses the concept of the unfolding U(S) of a schematic system S in order to describe those operations, predicates and principles concerning them, which are implicit in the acceptance of S. The program has been carried through for a schematic system of non-finitist arithmetic NFA in Feferman and Strahm (Ann Pure Appl Log, 104(1–3):75–96, 2000) and for a system FA (with and without Bar rule) in Feferman and Strahm (Rev Symb Log, 3(4):665–689, 2010). The present contribution elucidates the concept of unfolding for a basic schematic system FEA of feasible arithmetic. Apart from the operational unfolding U0(FEA) of FEA, we study two full unfolding notions, namely the predicate unfolding U(FEA) and a more general truth unfolding UT(FEA) of FEA, the latter making use of a truth predicate added to the language of the operational unfolding. The main results obtained are that the provably convergent functions on binary words for all three unfolding systems are precisely those being computable in polynomial time. The upper bound computations make essential use of a specific theory of truth TPT over combinatory logic, which has recently been introduced in Eberhard and Strahm (Bull Symb Log, 18(3):474–475, 2012) and Eberhard (A feasible theory of truth over combinatory logic, 2014) and whose involved proof-theoretic analysis is due to Eberhard (A feasible theory of truth over combinatory logic, 2014). The results of this paper were first announced in (Eberhard and Strahm, Bull Symb Log 18(3):474–475, 2012).