HIV-1 can escape from neutralizing antibodies rapidly during natural infection. Evolution of antibody escape is an important consideration for both vaccine and therapeutic development. Recent studies highlight both the potential strength of specific monoclonal antibody therapies for decreasing viral load and the need to understand virus escape in this setting. For envelope-based vaccine strategies, a greater understanding of both type- specific and more conserved neutralizing epitopes in addition to the evolution of these epitopes and the HIV envelope in response to selective pressure is critical in understanding and predicting vaccine efficacy. The pattern of virus envelope evolution, as a result of escape from antibody pressure, may be used ultimately to decipher the antibody specificities responsible for virus suppression and determine if a particular vaccine design or therapeutic regimen is potentially detrimental or highly beneficial to host survival. Integrative approaches using both traditional experimental methods and computational immunology for detailed mapping of virus envelope evolution in response to selective pressure may drive future innovations in HIV vaccines and therapeutic interventions.
Gradually typed languages allow programmers to mix statically and dynamically typed code, enabling them to incrementally reap the benefits of static typing as they add type annotations to their code. However, this type migration process is typically a manual effort with limited tool support. This paper examines the problem of \emph{automated type migration}: given a dynamic program, infer additional or improved type annotations. Existing type migration algorithms prioritize different goals, such as maximizing type precision, maintaining compatibility with unmigrated code, and preserving the semantics of the original program. We argue that the type migration problem involves fundamental compromises: optimizing for a single goal often comes at the expense of others. Ideally, a type migration tool would flexibly accommodate a range of user priorities. We present TypeWhich, a new approach to automated type migration for the gradually-typed lambda calculus with some extensions. Unlike prior work, which relies on custom solvers, TypeWhich produces constraints for an off-the-shelf MaxSMT solver. This allows us to easily express objectives, such as minimizing the number of necessary syntactic coercions, and constraining the type of the migration to be compatible with unmigrated code. We present the first comprehensive evaluation of GTLC type migration algorithms, and compare TypeWhich to four other tools from the literature. Our evaluation uses prior benchmarks, and a new set of ``challenge problems.'' Moreover, we design a new evaluation methodology that highlights the subtleties of gradual type migration. In addition, we apply TypeWhich to a suite of benchmarks for Grift, a programming language based on the GTLC. TypeWhich is able to reconstruct all human-written annotations on all but one program.
Given a set of candidate Datalog rules, the Datalog synthesis-as-rule-selection problem chooses a subset of these rules that satisfies a specification (such as an input-output example). Building off prior work using counterexample-guided inductive synthesis, we present a progression of three solver-based approaches for solving Datalog synthesis-as-rule-selection problems. Two of our approaches offer some advantages over existing approaches, and can be used more generally to solve arbitrary SMT formulas containing Datalog predicates; the third—an encoding into standard, off-the-shelf answer set programming (ASP)—leads to significant speedups (∼ 9× geomean) over the state of the art while synthesizing higher quality programs. Our progression of solutions explores the space of interactions between SAT/SMT and Datalog, identifying ASP as a promising tool for working with and reasoning about Datalog. Along the way, we identify Datalog programs as monotonic SMT theories, which enjoy particularly efficient interactions in SMT; our plugins for popular SMT solvers make it easy to load an arbitrary Datalog program into the SMT solver as a custom monotonic theory. Finally, we evaluate our approaches using multiple underlying solvers to provide a more thorough and nuanced comparison against the current state of the art.
Near the end of 1940 Friedrich Hauptmann secretly fled to his native Germany, forsaking Rutgers University where he was chairman of the German department at the New Jersey College for Women (N.J.C.). Despite having acquired American citizenship the previous year (several months before the start of World War II), Hauptmann traveled on a German passport, with expenses paid by the Hitler government. This was undoubtedly a reward for “serving ‘the cultural-political interests of the Reich’ in New Jersey.”
Erythropoietic and reticuloendothelial functions in bone marrow were found to be identically distributed between various bones and within individual bones in the dog.
Population considerations play a major role in the licensing of nuclear power stations. In the absence of systematic research, an understanding of what population changes have occurred in the vicinity of nuclear power stations is difficult. The method of population analysis utilized is a four-equation model that apportions local population change to components that can be accounted for by national, regional, county, and local trends. Population counts for 1960, 1970, and 1980 for host communities, host counties and adjacent counties were compiled from US Census data by Brookhaven National Laboratory. Application of the model to the population data shows a large component of unique local growth around the forty-eight sites during the 1970s. Site selection criteria used by the Nuclear Regulatory Commission emphasize the selection of low population areas in which little growth is anticipated. This research examines population growth after site selection for the period 1960 to 1980 for forty-three operating sites.
