Closed-loop Bayesian Semantic Data Fusion for Collaborative Human-Autonomy Target Search

In search applications, autonomous unmanned vehicles must be able to efficiently reacquire and localize mobile targets that can remain out of view for long periods of time in large spaces. As such, all available information sources must be actively leveraged -- including imprecise but readily available semantic observations provided by humans. To achieve this, this work develops and validates a novel collaborative human-machine sensing solution for dynamic target search. Our approach uses continuous partially observable Markov decision process (CPOMDP) planning to generate vehicle trajectories that optimally exploit imperfect detection data from onboard sensors, as well as semantic natural language observations that can be specifically requested from human sensors. The key innovation is a scalable hierarchical Gaussian mixture model formulation for efficiently solving CPOMDPs with semantic observations in continuous dynamic state spaces. The approach is demonstrated and validated with a real human-robot team engaged in dynamic indoor target search and capture scenarios on a custom testbed.Comment: Final version accepted and submitted to 2018 FUSION Conference (Cambridge, UK, July 2018

Fully Bayesian Human-Machine Data Fusion For Robust Dynamic Target Surveillance and Characterization

This work examines the problem of rigorously characterizing and fusing observations provided by human operators with probabilistic information extracted by an automated data fusion system, in the context of dynamic multi-target track characterization for large-scale surveillance. This task is characterized by three major challenges. Firstly, stand-alone human operator observation errors are difficult to parameterize and calibrate a priori. Secondly, successive single target observations from one operator are, in general, not conditionally independent of one another. Finally, the decision of when a human operator should assist the automation depends on the observed operator error characteristics as well as the uncertainty of the automation's track characterizations, all of which must be calculated online. A new hierarchical fully Bayesian probabilistic model is developed to explicitly account both for uncertainties in `human sensor' quality and Markovian conditional dependencies in successive target characterization reports. This model is used to perform online Bayesian inference via Gibbs sampling to simultaneously update the data fusion system's knowledge of human sensor characteristics and target type probabilities. The probabilistic model also allows for online Value of Information assessments to automatically query help from the human operator. Practical methods for approximating high-dimensional human sensor parameter posterior distributions via Dirichlet pdf moment-matching and parameter-tying are also developed, and shown to provide significant computational speedups for little/no noticeable information loss. These methods also demonstrate scalability with an increase in possible target types. Results with different combinations of simulated operator profiles and automated fusion system target characterization baselines show that fully Bayesian fusion can simultaneously improve machine-based characterization performance with variable human operator profiles, while accounting for uncertain operator characteristics.</p

Effect of DNA Repair Protein Rad18 on Viral Infection

Host factors belonging to the DNA repair machineries are assumed to aid retroviruses in the obligatory step of integration. Here we describe the effect of DNA repair molecule Rad18, a component of the post-replication repair pathway, on viral infection. Contrary to our expectations, cells lacking Rad18 were consistently more permissive to viral transduction as compared to Rad18(+/+) controls. Remarkably, such susceptibility was integration independent, since retroviruses devoid of integration activity also showed enhancement of the initial steps of infection. Moreover, the elevated sensitivity of the Rad18(−/−) cells was also observed with adenovirus. These data indicate that Rad18 suppresses viral infection in a non-specific fashion, probably by targeting incoming DNA. Furthermore, considering data published recently, it appears that the interactions between DNA repair components with incoming viruses, often result in inhibition of the infection rather than cooperation toward its establishment

NMR structure of a kissing complex formed between the TAR RNA element of HIV-1 and a LNA-modified aptamer

The trans-activating responsive (TAR) RNA element located in the 5′ untranslated region of the HIV-1 genome is a 57-nt imperfect stem-loop essential for the viral replication. TAR regulates transcription by interacting with both viral and cellular proteins. RNA hairpin aptamers specific for TAR were previously identified by in vitro selection [Ducongé,F. and Toulmé,J.J. (1999) In vitro selection identifies key determinants for loop-loop interactions: RNA aptamers selective for the TAR RNA element of HIV-1. RNA, 5, 1605–1614]. These aptamers display a 5′-GUCCCAGA-3′ consensus apical loop, partially complementary to the TAR one, leading to the formation of a TAR–aptamer kissing complex. The conserved GA combination (underlined in the consensus sequence) has been shown to be crucial for the formation of a highly stable complex. To improve the nuclease resistance of the aptamer and to increase its affinity for TAR, locked nucleic acid (LNA) nucleotides were introduced in the aptamer apical loop. LNA are nucleic acids analogues that contain a 2′-O,4′-C methylene linkage and that raise the thermostablity of duplexes. We solved the NMR solution structure of the TAR–LNA-modified aptamer kissing complex. Structural analysis revealed the formation of a non-canonical G•A pair leading to increased stacking at the stem-loop junction. Our data also showed that the introduction of LNA residues provides an enhanced stability while maintaining a normal Watson–Crick base pairing with a loop–loop conformation close to an A-type

A reflection on HIV/AIDS research after 25 years

Dr. Robert C. Gallo provides a personal reflection on the 25 year history of AIDS

HEXIM1 targets a repeated GAUC motif in the riboregulator of transcription 7SK and promotes base pair rearrangements

7SK snRNA, an abundant RNA discovered in human nucleus, regulates transcription by RNA polymerase II (RNAPII). It sequesters and inhibits the transcription elongation factor P-TEFb which, by phosphorylation of RNAPII, switches transcription from initiation to processive elongation and relieves pauses of transcription. This regulation process depends on the association between 7SK and a HEXIM protein, neither isolated partner being able to inhibit P-TEFb alone. In this work, we used a combined NMR and biochemical approach to determine 7SK and HEXIM1 elements that define their binding properties. Our results demonstrate that a repeated GAUC motif located in the upper part of a hairpin on the 5′-end of 7SK is essential for specific HEXIM1 recognition. Binding of a peptide comprising the HEXIM Arginine Rich Motif (ARM) induces an opening of the GAUC motif and stabilization of an internal loop. A conserved proline-serine sequence in the middle of the ARM is shown to be essential for the binding specificity and the conformational change of the RNA. This work provides evidences for a recognition mechanism involving a first event of induced fit, suggesting that 7SK plasticity is involved in the transcription regulation

HIVToolbox, an Integrated Web Application for Investigating HIV

Many bioinformatic databases and applications focus on a limited domain of knowledge federating links to information in other databases. This segregated data structure likely limits our ability to investigate and understand complex biological systems. To facilitate research, therefore, we have built HIVToolbox, which integrates much of the knowledge about HIV proteins and allows virologists and structural biologists to access sequence, structure, and functional relationships in an intuitive web application. HIV-1 integrase protein was used as a case study to show the utility of this application. We show how data integration facilitates identification of new questions and hypotheses much more rapid and convenient than current approaches using isolated repositories. Several new hypotheses for integrase were created as an example, and we experimentally confirmed a predicted CK2 phosphorylation site. Weblink: [http://hivtoolbox.bio-toolkit.com

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd