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

The Economic Impact of Failing Infrastructure in the New York Metropolitan Area

Infrastructure in the New York Metropolitan Area has been seriously underfunded due to a failure of public investment on the local, state and federal level. Prior research has presented concrete reasoning that the now crumbling infrastructure will seriously affect economic growth and worker productivity. This research seeks to quantify the economic effects as a result of this failing infrastructure. My research asks: what are the concrete, additional economic expenditures, due to failing infrastructure, that drivers spend each year? How much do these economic costs decrease our economic productivity, and how do the economic costs compare with proposed infrastructure improvements? From the research, it is evident drivers in the New York-Newark NY-NJ Metropolitan Statistical Area experience some of the highest of these costs than other areas in the Combined Statistical Area. It is projected the 2018 economic cost to these drivers will be $2,045 based on the value of one’s time lost spend in traffic. With a continued lack of investment, these costs are expected to grow due to continued infrastructure failure and a growing population. Various programs have been proposed to alleviate specific bottlenecks in the region, but a coordinated source of investment from local, state and federal levels remains a major issue in securing funding for these projects

Engaging Student Nurses in a Professional Association

Nicholas Craig discusses student engagement at Linfield College with regard to his involement with the Critical Care Nurses\u27 Club.https://digitalcommons.linfield.edu/inauguration2019_students/1004/thumbnail.jp

On geodesic ray bundles in hyperbolic groups

We construct a Cayley graph $\mathbf{Cay}_S(\Gamma)$ of a hyperbolic group $\Gamma$ such that there are elements $g,h\in\Gamma$ and a point $\gamma \in \partial_\infty\Gamma = \partial_\infty\mathbf{Cay}_S(\Gamma)$ such that the sets $\mathcal{RB}(g,\gamma)$ and $\mathcal{RB}(h,\gamma)$ in $\mathbf{Cay}_S(\Gamma)$ of vertices along geodesic rays from $g,h$ to $\gamma$ have infinite symmetric difference; thus answering a question of Huang, Sabok and Shinko.Comment: 9 pages, 7 figure

Queer Neo-Mexicanism: Negotiating Mexican and Gay Identities in the Art of Nahum B. Zenil and Julio Galán

The Mexican artists Nahum B. Zenil and Julio Galán have become the poster children for being gay and Mexican in contemporary art criticism. Critics have drawn comparisons between Zenil and Galán because of their thematic treatment of gay sexuality and Mexican nationalism. These comparisons, however, have often assumed that Zenil and Galán are representing a monolithic gay sexuality that is unaffected by their social class, their relationships to nationalism and Catholicism, and their views on the role of art in social activism. This paper aims to analyze specifically how Zenil and Galán represent two distinct gay identities, all the while employing the similar themes of suffering, the vulnerability of the gay male body, and the use of nationalist and Catholic symbols. Through a close reading of visual texts and the methodological lens of queer theory and art history, the paper will show that both artists represent homosexuality as a social construction that is influenced by the other identity categories the artists inhabit