Vaccinia protein C16 blocks innate immune sensing of DNA by binding the Ku complex

VACV gene C16L encodes a 37-kDa protein that is highly conserved in orthopoxviruses and functions as an immunomodulator. Intranasal infection of mice with a virus lacking C16L (vΔC16) induced less weight loss, fewer signs of illness and increased infiltration of leukocytes to the lungs compared with wild-type virus. To understand C16’s mechanism of action, tandem affinity purification and mass spectrometry were used to identify C16 binding partners. This revealed that Ku70, Ku80 and PHD2 interact with C16 in cells. Ku70 and Ku80 constitute the Ku heterodimer, a well characterised DNA repair complex. MEFs lacking Ku, or the other component of the DNA-dependent protein kinase (DNA-PK) complex, the catalytic subunit of DNA-PK (DNA-PKcs), were shown to be deficient in the upregulation of IRF-3-dependent genes such as Cxcl10, Il6 and Ifnb in response to transfection of DNA, but not poly (I:C). Furthermore, following infection of MEFs with VACV strain MVA the activation of Cxcl10 or Il6 transcription was dependent on DNA-PK. Therefore, DNA-PK is a DNA sensor capable of detecting poxvirus DNA and activating IRF-3-dependent innate immunity. C16 inhibited the binding of Ku to DNA, and therefore inhibited DNA-mediated induction of Cxcl10 and Il-6 in MEFs. The role of C16 in vivo was also examined: infection with vΔC16 led to increased production of Cxcl10 and Il-6 following intranasal infection of mice compared with wild-type virus. C16 is therefore an inhibitor of DNA-PK-mediated DNA sensing and innate immune activation. C16 was also shown to bind to PHD2, an enzyme involved in regulation of hypoxic signalling. VACV was found to activate the transcription of hypoxia-related genes, and C16 expression in cells was also capable of doing this. The role of hypoxic signalling in VACV infection remains poorly understood

A Quantum Algorithm To Locate Unknown Hashes For Known N-Grams Within A Large Malware Corpus

Quantum computing has evolved quickly in recent years and is showing significant benefits in a variety of fields. Malware analysis is one of those fields that could also take advantage of quantum computing. The combination of software used to locate the most frequent hashes and $n$-grams between benign and malicious software (KiloGram) and a quantum search algorithm could be beneficial, by loading the table of hashes and $n$-grams into a quantum computer, and thereby speeding up the process of mapping $n$-grams to their hashes. The first phase will be to use KiloGram to find the top-$k$ hashes and $n$-grams for a large malware corpus. From here, the resulting hash table is then loaded into a quantum machine. A quantum search algorithm is then used search among every permutation of the entangled key and value pairs to find the desired hash value. This prevents one from having to re-compute hashes for a set of $n$-grams, which can take on average $O(MN)$ time, whereas the quantum algorithm could take $O(\sqrt{N})$ in the number of table lookups to find the desired hash values.Comment: IEEE Quantum Week 2020 Conferenc

A construction of the quantum Steenrod squares and their algebraic relations

We construct a quantum deformation of the Steenrod square construction on closed monotone symplectic manifolds, based on the work of Fukaya, Betz and Cohen. We prove quantum versions of the Cartan and Adem relations. We compute the quantum Steenrod squares for all CP n and give the means of computation for all toric varieties. As an application, we also describe two examples of blowups along a subvariety, in which a quantum correction of the Steenrod square on the blowup is determined by the classical Steenrod square on the subvariety.Comment: 68 pages, 13 figures. v3: paper as accepted for publication by Geometry & Topology after peer review, uploaded as per MSP open-access policy. Changes: the title is now correctly capitalised. Updated contact details in the paper. Multiple small changes were made across the paper since v2, mainly to make the exposition cleare

The Political Economy of the Research Exemption in American Patent Law

This Article approaches the research exemption, and related legal developments, as a case study in the political economy of patent law. Part I recounts the history of the research exemption, touching briefly on historical origins but emphasizing developments since the 1970s in legislative, executive, and judicial forums. It also examines changes during the same time frame in related areas of patent law, like the Bayh-Dole legislation and the attempted repeal of state immunity from patent infringement liability. These legal developments indirectly affected the research exemption, or implicated similar concerns about imbalance in the patent system and the use of patents to tax, control, or inhibit research activity. Part II analyzes this history to illustrate and expand upon two major themes in the political economy of patent law, namely the surprising persistence of faulty economic ideology in patent policymaking and the institutional bias exhibited by the Court of Appeals for the Federal Circuit in shaping modern patent law. One major conclusion is that together these forces have created an excessively complex and ill-designed policy environment that is placing a significant strain on the national research system, a strain that executive agencies and the courts have tried to alleviate through ad hoc agreements and modifications of other patent doctrines, like the doctrine of subject matter eligibility

On the one-endedness of graphs of groups

We give a technical result that implies a straightforward necessary and sufficient conditions for a graph of groups with virtually cyclic edge groups to be one ended. For arbitrary graphs of groups, we show that if their fundamental group is not one-ended, then we can blow up vertex groups to graphs of groups with simpler vertex and edge groups. As an application, we generalize a theorem of Swarup to decompositions of virtually free groups.Comment: Improved exposition. 17 pages, 7 figures. To appear in Pacific J. Mat

The Dr Elizabeth Casson Memorial Lecture 2018: Occupational stories from a global city

The Dr Elizabeth Casson Memorial Lecture 2018, given on June 12th 2018 at the 42nd Annual Conference and Exhibition of the Royal College of Occupational Therapists, held at the Belfast Waterfront, Belfast, UK. This lecture aims to set out the potential for the global occupational therapy profession to exchange knowledge for social transformation practice. It identifies the profession’s concern with narratives as a vehicle for a socially critical approach to occupation, which can be used to negotiate intervention and action. Drawing on examples from literature, history and service users, the paper suggests that narrative provides a means for relating the value of occupation beyond professional boundaries to capture popular imagination and demand for the profession. Examples are given of the critical discussion of the everyday impact of health inequity, and in addressing diversity both in the profession and engaging service users. My lecture concludes that occupational therapy is a global network with the population of a city, and thus represents a community that can be a vibrant voice for social transformation through occupation through a reciprocal exchange of narrative. This is a collective and dialogical process which can draw on the experiences of both southern and northern hemispheres

Levinson on the Aesthetic Ideal

In “Artistic Worth and Personal Taste,” Jerrold Levinson develops a problem for those who think we should strive to be “ideal critics” in our aesthetic lives. He then offers several solutions to this problem. I argue that his solutions miss the mark and that the problem he characterizes may not be genuine after all

Rus v Comcare: The Rules of Evidence in the AAT

The Rus v Comcare cases arise from a claim for compensation by the widowed Ms Rus. The cases saw a highly contentious piece of evidence tendered. This evidence was hearsay of a lay opinion that answered the ultimate issue. The evidence was considered by the Administrative Appeals Tribunal (‘AAT’) and the Federal Court of Australia (‘Court’). These considerations demonstrate the uncertainty of how the rules of evidence are applicable in tribunals. Specifically, the cases raise applicability of the rules against opinion and hearsay evidence. Further, the relevance of delay and the parol evidence rule to these cases is raised. The principles and policies governing these issues are analysed, which warranted minimal if any discussion in the cases, to assist practitioners in similar cases