Myxoma virus protein M029 is a dual function immunomodulator that inhibits PKR and also conscripts RHA/DHX9 to promote expanded host tropism and viral replication.

Myxoma virus (MYXV)-encoded protein M029 is a member of the poxvirus E3 family of dsRNA-binding proteins that antagonize the cellular interferon signaling pathways. In order to investigate additional functions of M029, we have constructed a series of targeted M029-minus (vMyx-M029KO and vMyx-M029ID) and V5-tagged M029 MYXV. We found that M029 plays a pivotal role in determining the cellular tropism of MYXV in all mammalian cells tested. The M029-minus viruses were able to replicate only in engineered cell lines that stably express a complementing protein, such as vaccinia E3, but underwent abortive or abated infection in all other tested mammalian cell lines. The M029-minus viruses were dramatically attenuated in susceptible host European rabbits and caused no observable signs of myxomatosis. Using V5-tagged M029 virus, we observed that M029 expressed as an early viral protein is localized in both the nuclear and cytosolic compartments in virus-infected cells, and is also incorporated into virions. Using proteomic approaches, we have identified Protein Kinase R (PKR) and RNA helicase A (RHA)/DHX9 as two cellular binding partners of M029 protein. In virus-infected cells, M029 interacts with PKR in a dsRNA-dependent manner, while binding with DHX9 was not dependent on dsRNA. Significantly, PKR knockdown in human cells rescued the replication defect of the M029-knockout viruses. Unexpectedly, this rescue of M029-minus virus replication by PKR depletion could then be reversed by RHA/DHX9 knockdown in human monocytic THP1 cells. This indicates that M029 not only inhibits generic PKR anti-viral pathways, but also binds and conscripts RHA/DHX9 as a pro-viral effector to promote virus replication in THP1 cells. Thus, M029 is a critical host range and virulence factor for MYXV that is required for replication in all mammalian cells by antagonizing PKR-mediated anti-viral functions, and also conscripts pro-viral RHA/DHX9 to promote viral replication specifically in myeloid cells

A fully integrated paperfluidic molecular diagnostic chip for the extraction, amplification, and detection of nucleic acids from clinical samples

Paper diagnostics have successfully been employed to detect the presence of antigens or small molecules in clinical samples through immunoassays; however, the detection of many disease targets relies on the much higher sensitivity and specificity achieved via nucleic acid amplification tests (NAAT). The steps involved in NAAT have recently begun to be explored in paper matrices, and our group, among others, has reported on paper-based extraction, amplification, and detection of DNA and RNA targets. Here, we integrate these paper-based NAAT steps into a single paperfluidic chip in a modular, foldable system that allows for fully integrated fluidic handling from sample to result. We showcase the functionality of the chip by combining nucleic acid isolation, isothermal amplification, and lateral flow detection of human papillomavirus (HPV) 16 DNA directly from crude cervical specimens in less than 1 hour for rapid, early detection of cervical cancer. The chip is made entirely of paper and adhesive sheets, making it low-cost, portable, and disposable, and offering the potential for a point-of-care molecular diagnostic platform even in remote and resource-limited settings.U54 EB015403 - NIBIB NIH HHS; U54 EB015408 - NIBIB NIH HHS; U54-EB015403-S1 - NIBIB NIH HH

The Contribution of Population Health and Demographic Change to Economic Growth in China and India

We find that a cross-country model of economic growth successfully tracks the growth takeoffs in China and India. The major drivers of the predicted takeoffs are improved health, increased openness to trade, and a rising labor force-to-population ratio due to fertility decline. We also explore the effect of the reallocation of labor from low-productivity agriculture to the higher productivity industry and service sectors. Including the money value of longevity improvements in a measure of full income reduces the gap between the magnitude of China's takeoff relative to India's due to the relative stagnation in life expectancy in China since 1980.aging, health, retirement

Asuminen kielialueittain Helsingissä - Harjoitustyö

Peer reviewe

A randomised comparison of three different immobilisation devices for thoracic and abdominal cancers

Introduction: Patient immobilisation is critically important for both highly conformal conventionally fractionated radiotherapy and for stereotactic body radiotherapy. Different immobilisation devices are available to maintain patient position for radiotherapy but the most suitable one remains unknown. Methods: Forty-five patients were randomly allocated to one of three immobilisation devices; the Q fix arm shuttle, BodyFIX without wrap or BodyFIX with wrap. Patients were imaged before and after treatment to ascertain intra-fraction and inter-fraction motion. Bony anatomy was used for matching to determine the positional accuracy of each device. Treatments were timed using a standard method. Patient comfort and staff satisfaction questionnaires were also issued to determine comfort, ease of use and preferences for each device. Results: The BodyFIX without wrap was the more accurate device; however, the differences between the devices were not statistically significant. The BodyFIX with wrap was found to take significantly longer to set up and set down compared to the arm shuttle and the BodyFIX without wrap (all P < 0.001). Patients (37%) marginally preferred the BodyFIX with wrap. Most (81%) staff preferred the BodyFIX without wrap. Conclusion: Immobilisation using the BodyFIX without wrap was deemed to be suitable for clinical use. It was a clinically accurate device, the more efficient in terms of set up and set down time, the most preferred by staff and was accepted by patients

2013-2014 Music of the Mind: From the Studio of Roberta Rust

https://spiral.lynn.edu/conservatory_otherseasonalconcerts/1012/thumbnail.jp

Cryptographically Secure Information Flow Control on Key-Value Stores

We present Clio, an information flow control (IFC) system that transparently incorporates cryptography to enforce confidentiality and integrity policies on untrusted storage. Clio insulates developers from explicitly manipulating keys and cryptographic primitives by leveraging the policy language of the IFC system to automatically use the appropriate keys and correct cryptographic operations. We prove that Clio is secure with a novel proof technique that is based on a proof style from cryptography together with standard programming languages results. We present a prototype Clio implementation and a case study that demonstrates Clio's practicality.Comment: Full version of conference paper appearing in CCS 201

Circular Optical Phased Array with Large Steering Range and High Resolution

Light detection and ranging systems based on optical phased arrays and integrated silicon photonics have sparked a surge of applications over the recent years. This includes applications in sensing, free-space communications, or autonomous vehicles, to name a few. Herein, we report a design of two-dimensional optical phased arrays, which are arranged in a grid of concentric rings. We numerically investigate two designs composed of 110 and 820 elements, respectively. Both single-wavelength (1550 nm) and broadband multi-wavelength (1535 nm to 1565 nm) operations are studied. The proposed phased arrays enable free-space beam steering, offering improved performance with narrow beam divergences of only 0.5° and 0.22° for the 110-element and 820-element arrays, respectively, with a main-to-sidelobe suppression ratio higher than 10 dB. The circular array topology also allows large element spacing far beyond the sub-wavelength-scaled limits that are present in one-dimensional linear or two-dimensional rectangular arrays. Under a single-wavelength operation, a solid-angle steering between 0.21π sr and 0.51π sr is obtained for 110- and 820-element arrays, respectively, while the beam steering spans the range of 0.24π sr and 0.57π sr for a multi-wavelength operation. This work opens new opportunities for future optical phased arrays in on-chip photonic applications, in which fast, high-resolution, and broadband beam steering is necessary.This work was supported by the Natural Sciences and Engineering Research Council of Canada’s Collaborative R&D Grant Program by collaborating with Optiwave Systems, Inc., Slovak Grant Agency VEGA 1/0113/22, and Slovak Research and Development Agency under the project APVV-21-0217. Partial funding for open access charge: Universidad de Málag

Characterization of Patients With Axial Spondyloarthritis by Enthesitis Presence: Data from the Corrona Psoriatic Arthritis/Spondyloarthritis Registry.

OBJECTIVE: To compare the characteristics of patients with axial spondyloarthritis (axSpA) who had enthesitis versus those without enthesitis. METHODS: This study included adult patients with axSpA enrolled in the Corrona Psoriatic Arthritis/Spondyloarthritis Registry (March 2013 to August 2018). Enthesitis was assessed at enrollment via the Spondyloarthritis Research Consortium of Canada Enthesitis Index. Characteristics were compared between patients with and without enthesitis using t tests or Wilcoxon rank-sum tests for continuous variables and χ RESULTS: Of 477 patients with axSpA, 121 (25.4%) had enthesitis (mean, 3.9 sites) at enrollment. Higher proportions of patients with enthesitis were female and had nonradiographic axSpA than those without enthesitis (both P \u3c 0.05). Additionally, higher proportions of patients with enthesitis had prior biologic (38.8% vs 27.2%) and conventional synthetic disease-modifying antirheumatic drug (csDMARD; 24.8% vs 13.3%) use and were currently receiving a combination of biologics and csDMARDs (28.6% vs 18.1%) than those without enthesitis. Patients with enthesitis had worse disease activity (tender and swollen joint counts, physician global assessment, Ankylosing Spondylitis Disease Activity Score, Bath Ankylosing Spondylitis Disease Activity Index, and Bath Ankylosing Spondylitis Functional Index), spinal mobility, and quality of life (pain, fatigue, Health Assessment Questionnaire, and EuroQol visual analog scale scores); greater work impairment; and had a history of depression and fibromyalgia than those without enthesitis (all P \u3c 0.05). CONCLUSION: In this US-based real-world study, enthesitis in patients with axSpA was associated with worse disease activity and quality of life than those with no enthesitis