Specifying and Executing Optimizations for Parallel Programs

Compiler optimizations, usually expressed as rewrites on program graphs, are a core part of all modern compilers. However, even production compilers have bugs, and these bugs are difficult to detect and resolve. The problem only becomes more complex when compiling parallel programs; from the choice of graph representation to the possibility of race conditions, optimization designers have a range of factors to consider that do not appear when dealing with single-threaded programs. In this paper we present PTRANS, a domain-specific language for formal specification of compiler transformations, and describe its executable semantics. The fundamental approach of PTRANS is to describe program transformations as rewrites on control flow graphs with temporal logic side conditions. The syntax of PTRANS allows cleaner, more comprehensible specification of program optimizations; its executable semantics allows these specifications to act as prototypes for the optimizations themselves, so that candidate optimizations can be tested and refined before going on to include them in a compiler. We demonstrate the use of PTRANS to state, test, and refine the specification of a redundant store elimination optimization on parallel programs.Comment: In Proceedings GRAPHITE 2014, arXiv:1407.767

Verifying Optimizations for Concurrent Programs

While program correctness for compiled languages depends fundamentally on compiler correctness, compiler optimizations are not usually formally verified due to the effort involved, particularly in the presence of concurrency. In this paper, we present a framework for stating and reasoning about compiler optimizations and transformations on programs in the presence of relaxed memory models. The core of the framework is the PTRANS specification language, in which program transformations are expressed as rewrites on control flow graphs with temporal logic side conditions. We demonstrate our technique by verifying the correctness of a redundant store elimination optimization in a simple LLVM-like intermediate language, relying on a theorem that allows us to lift single-thread simulation relations to simulations on multithreaded programs

Autoinflammatory Disease Reloaded: A Clinical Perspective

Our understanding of the etiology of autoinflammatory disease is growing rapidly. Recent advances offer new opportunities for therapeutic intervention and suggest that the definition of what constitutes an autoinflammatory disease should be reassessed

Broadening the use of antiretroviral therapy: the case for feline leukemia virus

Antiretroviral drugs have saved and extended the lives of millions of individuals infected with HIV. The major classes of anti-HIV drugs include reverse transcriptase inhibitors, protease inhibitors, integrase inhibitors, and entry/fusion inhibitors. While antiretroviral drug regimens are not commonly used to treat other types of retroviral infections, there are instances where there is a perceived need for re-evaluation of the benefits of antiretroviral therapy. One case in point is that of feline leukemia virus (FeLV), an infection of companion felines. While vaccines exist to prevent FeLV infection and spread, they have not eliminated FeLV infection. For FeLV-infected felines and their human companions, antiretroviral therapy would be desirable and of practical importance if good options were available. Here, we discuss FeLV biology and current treatment options, and propose that there is a need for antiretroviral treatment options for FeLV infection. The comparative use and analysis of antiretroviral therapy can provide new insights into the mechanism of antiretroviral drug action

Mathematical modeling of escape of HIV from cytotoxic T lymphocyte responses

Human immunodeficiency virus (HIV-1 or simply HIV) induces a persistent infection, which in the absence of treatment leads to AIDS and death in almost all infected individuals. HIV infection elicits a vigorous immune response starting about 2-3 weeks post infection that can lower the amount of virus in the body, but which cannot eradicate the virus. How HIV establishes a chronic infection in the face of a strong immune response remains poorly understood. It has been shown that HIV is able to rapidly change its proteins via mutation to evade recognition by virus-specific cytotoxic T lymphocytes (CTLs). Typically, an HIV-infected patient will generate 4-12 CTL responses specific for parts of viral proteins called epitopes. Such CTL responses lead to strong selective pressure to change the viral sequences encoding these epitopes so as to avoid CTL recognition. Here we review experimental data on HIV evolution in response to CTL pressure, mathematical models developed to explain this evolution, and highlight problems associated with the data and previous modeling efforts. We show that estimates of the strength of the epitope-specific CTL response depend on the method used to fit models to experimental data and on the assumptions made regarding how mutants are generated during infection. We illustrate that allowing CTL responses to decay over time may improve the fit to experimental data and provides higher estimates of the killing efficacy of HIV-specific CTLs. We also propose a novel method for simultaneously estimating the killing efficacy of multiple CTL populations specific for different epitopes of HIV using stochastic simulations. Lastly, we show that current estimates of the efficacy at which HIV-specific CTLs clear virus-infected cells can be improved by more frequent sampling of viral sequences and by combining data on sequence evolution with experimentally measured CTL dynamics

Symbolic Semantics for CSP

Communicating Sequential Processes (CSP) is a well-known formal language for describing concur- rent systems. Brookes, Hoare and Roscoe [2] have given a transition semantics for CSP that underlies common approaches to model checking properties of CSP programs. In this paper, we present a gen- eralized transition semantics of CSP, which we call HCSP, that merges the original transition system with ideas from Floyd-Hoare Logic and symbolic computation. This generalized semantics is shown to be sound and complete with respect to the original trace semantics. Traces in our system are sym- bolic representations of families of traces as given by the original semantics. This more compact representation allows us to expand the original CSP systems to effectively model check some CSP programs which are difficult for other CSP systems to analyze. In particular, our system can han- dle certain classes of non-deterministic choices as a single transition, while the original semantics would treat each choice separately, possibly leading to large or unbounded case analyses. All work described in this paper has been carried out in the theorem prover Isabelle. This then provides us with a framework for automated and interactive analysis of CSP processes. It also give us the ability to extract Ocaml code for an HCSP-based simulator directly from Isabelle.NSF 0917218NASA Contract NNA10DE79Cunpublishednot peer reviewe

Evidence of Andreev bound states as a hallmark of the FFLO phase in κ\kappa-(BEDT-TTF)2_2Cu(NCS)2_2

Superconductivity is a quantum phenomena arising, in its simplest form, from pairing of fermions with opposite spin into a state with zero net momentum. Whether superconductivity can occur in fermionic systems with unequal number of two species distinguished by spin, atomic hyperfine states, flavor, presents an important open question in condensed matter, cold atoms, and quantum chromodynamics, physics. In the former case the imbalance between spin-up and spin-down electrons forming the Cooper pairs is indyced by the magnetic field. Nearly fifty years ago Fulde, Ferrell, Larkin and Ovchinnikov (FFLO) proposed that such imbalanced system can lead to exotic superconductivity in which pairs acquire finite momentum. The finite pair momentum leads to spatially inhomogeneous state consisting of of a periodic alternation of "normal" and "superconducting" regions. Here, we report nuclear magnetic resonance (NMR) measurements providing microscopic evidence for the existence of this new superconducting state through the observation of spin-polarized quasiparticles forming so-called Andreev bound states.Comment: 6 pages, 5 fig

New Insights into HTLV-1 Particle Structure, Assembly, and Gag-Gag Interactions in Living Cells

Human T-cell leukemia virus type 1 (HTLV-1) has a reputation for being extremely difficult to study in cell culture. The challenges in propagating HTLV-1 has prevented a rigorous analysis of how these viruses replicate in cells, including the detailed steps involved in virus assembly. The details for how retrovirus particle assembly occurs are poorly understood, even for other more tractable retroviral systems. Recent studies on HTLV-1 using state-of-the-art cryo-electron microscopy and fluorescence-based biophysical approaches explored questions related to HTLV-1 particle size, Gag stoichiometry in virions, and Gag-Gag interactions in living cells. These results provided new and exciting insights into fundamental aspects of HTLV-1 particle assembly—which are distinct from those of other retroviruses, including HIV-1. The application of these and other novel biophysical approaches promise to provide exciting new insights into HTLV-1 replication

Modeling viral coevolution: HIV multi-clonal persistence and competition dynamics

The coexistence of different viral strains (quasispecies) within the same host are nowadays observed for a growing number of viruses, most notably HIV, Marburg and Ebola, but the conditions for the formation and survival of new strains have not yet been understood. We present a model of HIV quasispecies competition, that describes the conditions of viral quasispecies coexistence under different immune system conditions. Our model incorporates both T and B cells responses, and we show that the role of B cells is important and additive to that of T cells. Simulations of coinfection (simultaneous infection) and superinfection (delayed secondary infection) scenarios in the early stages (days) and in the late stages of the infection (years) are in agreement with emerging molecular biology findings. The immune response induces a competition among similar phenotypes, leading to differentiation (quasi-speciation), escape dynamics and complex oscillations of viral strain abundance. We found that the quasispecies dynamics after superinfection or coinfection has time scales of several months and becomes even slower when the immune system response is weak. Our model represents a general framework to study the speed and distribution of HIV quasispecies during disease progression, vaccination and therapy.Comment: 20 pages, 10 figure