Crypto-Verifying Protocol Implementations in ML

We intend to narrow the gap between concrete implementations and verified models of cryptographic protocols. We consider protocols implemented in F#, a variant of ML, and verified using CryptoVerif, Blanchet's protocol verifier for computational cryptography. We experiment with compilers from F# code to CryptoVerif processes, and from CryptoVerif declarations to F# code. We present two case studies: an implementation of the Otway-Rees protocol, and an implementation of a simplified password-based authentication protocol. In both cases, we obtain concrete security guarantees for a computational model closely related to executable code

Complete Genome Sequence of a Divergent Human Rhinovirus C Isolate from an Infant with Severe Community-Acquired Pneumonia in Colorado, USA.

Here, we report the genome sequence of a divergent human rhinovirus C isolate identified from an infant with a severe community-acquired respiratory infection. RNA sequencing performed on an Illumina platform identified reads aligning to human rhinovirus species, which were de novo assembled to produce a coding-complete genome sequence

Search for the standard model production of a single top quark in association with a Z0 boson using machine learning techniques

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University London.This thesis presents a search for the production of a single top quark in association with a Z0 boson in the dileptonic decay channel as predicted by the Standard Model. The search uses 77.8 fb−1 of data from √ = 13 TeV proton– proton collisions collected by the Compact Muon Solenoid experiment at the Large Hadron Collider during the 2016–2017 data-taking period. The search identified events containing a Z0 boson decay by requiring two opposite-sign same-flavour electrons or muons in the final state with invariant mass compatible with the nominal Z0 boson mass. Products of the top quark decay were identified using techniques developed to identify jets originating from bottom quarks and searching for a jet pair with invariant mass compatible with the W± boson mass. Machine learning techniques were used to further discriminate the signal process from background events. A study was carried out, comparing the performance of boosted decision trees with hyperparameters optimised using a Gaussian process and multi-layer perceptrons on this problem. The boosted decision trees were found to outperform the multi-layer perceptrons. A signal strength of ̂ = 6.52+2.30 −2.05 was observed, where ̂ = 1.0 corresponds to the Standard Model expectation. The corresponding observed (expected) significance is 3.12 (0.48).Science and Technologies Facilities Counci

Envelope determinants of equine lentiviral vaccine protection

Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection

Complex Tissue Regeneration in Mammals Is Associated with Reduced Inflammatory Cytokines and an Influx of T Cells

While mammals tend to repair injuries, other adult vertebrates like salamanders and fish regenerate damaged tissue. One prominent hypothesis offered to explain an inability to regenerate complex tissue in mammals is a bias during healing toward strong adaptive immunity and inflammatory responses. Here we directly test this hypothesis by characterizing part of the immune response during regeneration in spiny mice (Acomys cahirinus and Acomys percivali) vs. fibrotic repair in Mus musculus. By directly quantifying cytokines during tissue healing, we found that fibrotic repair was associated with a greater release of pro-inflammatory cytokines (i.e., IL-6, CCL2, and CXCL1) during acute inflammation in the wound microenvironment. However, reducing inflammation via COX-2 inhibition was not sufficient to reduce fibrosis or induce a regenerative response, suggesting that inflammatory strength does not control how an injury heals. Although regeneration was associated with lower concentrations of many inflammatory markers, we measured a comparatively larger influx of T cells into regenerating ear tissue and detected a local increase in the T cell associated cytokines IL-12 and IL-17 during the proliferative phase of regeneration. Taken together, our data demonstrate that a strong adaptive immune response is not antagonistic to regeneration and that other mechanisms likely explain the distribution of regenerative ability in vertebrates

AnBx - Security Protocols Design and Verification

Designing distributed protocols is challenging, as it requires actions at very different levels: from the choice of network-level mechanisms to protect the exchange of sensitive data, to the definition of structured interaction patterns to convey application-specific guarantees. Current security infrastructures provide very limited support for the specification of such guarantees. As a consequence, the high-level security properties of a protocol typically must often be hard-coded explicitly, in terms of low-level cryptographic notions and devices which clutter the design and undermine its scalability and robustness. To counter these problems, we propose an extended Alice & Bob notation for protocol narrations (AnBx) to be employed for a purely declarative modelling of distributed protocols. These abstractions provide a compact specification of the high-level security guarantees they convey, and help shield the design from the details of the underlying cryptographic infrastructure. We discuss an implementation of the abstractions based on a translation from the AnBx notation to the AnB language supported by the OFMC [1,2] verification tool. We show the practical effectiveness of our approach by revisiting the iKP e-payment protocols, and showing that the security goals achieved by our declarative specification outperform those offered by the original protocols

Envelope Determinants of Equine Lentiviral Vaccine Protection

Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection. © 2013 Craigo et al

Designer Lipid-Like Peptides: A Class of Detergents for Studying Functional Olfactory Receptors Using Commercial Cell-Free Systems

A crucial bottleneck in membrane protein studies, particularly G-protein coupled receptors, is the notorious difficulty of finding an optimal detergent that can solubilize them and maintain their stability and function. Here we report rapid production of 12 unique mammalian olfactory receptors using short designer lipid-like peptides as detergents. The peptides were able to solubilize and stabilize each receptor. Circular dichroism showed that the purified olfactory receptors had alpha-helical secondary structures. Microscale thermophoresis suggested that the receptors were functional and bound their odorants. Blot intensity measurements indicated that milligram quantities of each olfactory receptor could be produced with at least one peptide detergent. The peptide detergents' capability was comparable to that of the detergent Brij-35. The ability of 10 peptide detergents to functionally solubilize 12 olfactory receptors demonstrates their usefulness as a new class of detergents for olfactory receptors, and possibly other G-protein coupled receptors and membrane proteins.United States. Defense Advanced Research Projects Agency (DARPA-HR0011-09-C-0012)Massachusetts Institute of Technology. Undergraduate Research Opportunities Progra

A global resource for genomic predictions of antimicrobial resistance and surveillance of Salmonella Typhi at pathogenwatch.

As whole-genome sequencing capacity becomes increasingly decentralized, there is a growing opportunity for collaboration and the sharing of surveillance data within and between countries to inform typhoid control policies. This vision requires free, community-driven tools that facilitate access to genomic data for public health on a global scale. Here we present the Pathogenwatch scheme for Salmonella enterica serovar Typhi (S. Typhi), a web application enabling the rapid identification of genomic markers of antimicrobial resistance (AMR) and contextualization with public genomic data. We show that the clustering of S. Typhi genomes in Pathogenwatch is comparable to established bioinformatics methods, and that genomic predictions of AMR are highly concordant with phenotypic susceptibility data. We demonstrate the public health utility of Pathogenwatch with examples selected from >4,300 public genomes available in the application. Pathogenwatch provides an intuitive entry point to monitor of the emergence and spread of S. Typhi high risk clones

Metrics of salbutamol use as predictors of future adverse outcomes in asthma

Background Beta-agonist overuse is associated with adverse outcomes in asthma, however, the relationships between different metrics of salbutamol use and future risk are uncertain. Objective To investigate the relationship between metrics of salbutamol use and adverse outcome. Methods In a 24-week randomized controlled trial of 303 asthma patients at risk of severe exacerbations which compared the efficacy and safety of combination budesonide/formoterol inhaler according to a single inhaler regimen (SMART) with a fixed-dose regimen with salbutamol as reliever (‘Standard’), actual medication use was measured by electronic monitoring (Australian New Zealand Clinical Trials Registry Number ACTRN12610000515099). A nested cohort study explored the relationship between metrics of baseline salbutamol use over 2 weeks and future severe asthma exacerbations, poor asthma control (ACQ-5 ≥ 1.5) or ‘extreme’ salbutamol overuse (> 32 salbutamol actuations/24-h period). Results Higher mean daily salbutamol use (per two actuations/day) [Odds ratio (OR) (95% CI) 1.24 (1.06–1.46)], higher days of salbutamol use (per 2 days in 2 weeks) [OR 1.15 (1.00–1.31)] and higher maximal 24-h use (per two actuations/day) [OR 1.09 (1.02–1.16)] were associated with future severe exacerbations. Higher mean daily salbutamol use was associated with future poor asthma control [OR 1.13 (1.02–1.26)]. Higher mean daily salbutamol use [OR 2.73 (1.84–4.07)], number of days of use [OR 1.46 (1.24–1.71)], and maximal daily use [OR 1.57 (1.31–1.89)] were associated with an increased risk of future extreme salbutamol overuse. Conclusion and Clinical Relevance Electronically recorded frequency of current salbutamol use is a strong predictor of risk of future adverse outcomes in asthma, with average daily use performing the best. These findings provide new information for clinicians considering metrics of salbutamol as predictors of future adverse outcomes in asthma