Poly(2-propylacrylic acid)/poly(lactic-co-glycolic acid) blend microparticles as a targeted antigen delivery system to direct either CD4+ or CD8+ T cell activation.

Poly(lactic-co-glycolic acid) (PLGA) based microparticles (MPs) are widely investigated for their ability to load a range of molecules with high efficiency, including antigenic proteins, and release them in a controlled manner. Micron-sized PLGA MPs are readily phagocytosed by antigen presenting cells, and localized to endosomes. Due to low pH and digestive enzymes, encapsulated protein cargo is largely degraded and processed in endosomes for MHC-II loading and presentation to CD4+ T cells, with very little antigen delivered into the cytosol, limiting MHC-I antigenic loading and presentation to CD8+ T cells. In this work, PLGA was blended with poly(2-propylacrylic acid) (PPAA), a membrane destabilizing polymer, in order to incorporate an endosomal escape strategy into PLGA MPs as an easily fabricated platform with diverse loading capabilities, as a means to enable antigen presentation to CD8+ T cells. Ovalbumin (OVA)-loaded MPs were fabricated using a water-in-oil double emulsion with a 0% (PLGA only), 3 and 10% PPAA composition. MPs were subsequently determined to have an average diameter of 1 µm, with high loading and a release profile characteristic of PLGA. Bone marrow derived dendritic cells (DCs) were then incubated with MPs in order to evaluate localization, processing, and presentation of ovalbumin. Endosomal escape of OVA was observed only in DC groups treated with PPAA/PLGA blends, which promoted high levels of activation of CD8+ OVA-specific OT-I T cells, compared to DCs treated with OVA-loaded PLGA MPs which were unable activate CD8+ T cells. In contrast, DCs treated with OVA-loaded PLGA MPs promoted OVA-specific OT-II CD4+ T cell activation, whereas PPAA incorporation into the MP blend did not permit CD4+ T cell activation. These studies demonstrate PLGA MP blends containing PPAA are able to provide an endosomal escape strategy for encapsulated protein antigen, enabling the targeted delivery of antigen for tunable presentation and activation of either CD4+ or CD8+ T cells

Implications of antimicrobial combinations in complex wound biofilms containing fungi

Diabetic foot ulcer treatment currently focuses on targeting bacterial biofilms, while dismissing fungi. To investigate this we used an in vitro biofilm model containing bacteria and fungi, reflective of the wound environment, to test the impact of antimicrobials. Here we showed that while mono-treatment approaches influenced biofilm composition it had no discernible effect on overall quantity. Only by combining bacterial and fungal specific antibiotics were we able to decrease the biofilm bioburden, irrespective of composition

Starling1: Swarm Technology Demonstration

The Starling series of demonstration missions will test technologies required to achieve affordable, distributed spacecraft (“swarm”) missions that: are scalable to at least 100 spacecraft for applications that include synchronized multipoint measurements; involve closely coordinated ensembles of two or more spacecraft operating as a single unit for interferometric, synthetic aperture, or similar sensor architectures; or use autonomous or semi-autonomous operation of multiple spacecraft functioning as a unit to achieve science or other mission objectives with low-cost small spacecraft. Starling1 will focus on developing technologies that enable scalability and deep space application. The mission goals include the demonstration of a Mobile Ad-hoc NETwork (MANET) through an in-space communication experiment and vision based relative navigation through the Starling Formation-flying Optical eXperiment (StarFOX)

Flexible Work Arrangements and Employee Work Attitudes: A Case-Based Inquiry of a Small Non-Profit Response to Crisis

We conducted an exploratory case-based study to examine the impact of adopting flexible work arrangements strategies in response to the Covid-19 pandemic on employee work attitudes for a small, regional non-profit. Our findings indicated the importance of managerial support and organizational commitment to moderate the relationship between flexible work arrangements and job satisfaction. We also explored the influence of technology efficacy and work-life balance on the model. Our paper provides support for the prior empirical and theoretical assumptions that flexible work arrangements can have a positive impact on employee work attitudes and may be an effective managerial tool in response to a crisis

Qualitative spatial representation in agent-based models

One of the advantages of agent-based models as simulations of social systems is the ease with which it is possible to spatially embed the agents and their interactions. Spatially explicit representations in agent-based models most typically take the form of raster-based representations in which the space is represented as a grid of squares. More recently, vectorbased representations have been used, usually importing data for the polygons from geographical information systems (GIS). However, for some models, what matters about the space for the purposes of simulation is less the quantitative spatial relationships among entities (e.g. area, distance or direction) than the qualitative relations these quantitative data are used to determine: neighbourhood, and accessibility (which is a general term covering movement and sensing from one region to another). This paper gives consideration to the use of qualitative spatial representations in agent-based modelling, using a model of everyday pro-environmental behaviour in the workplace as an example

Finalizing the CCSDS Space-Data Link Layer Security Protocol: Setup and Execution of the Interoperability Testing

The protection of data transmitted over the space-link is an issue of growing importance also for civilian space missions. Through the Consultative Committee for Space Data Systems (CCSDS), space agencies have reacted to this need by specifying the Space Data-Link Layer Security (SDLS) protocol which provides confidentiality and integrity services for the CCSDS Telemetry (TM), Telecommand (TC) and Advanced Orbiting Services (AOS) space data-link protocols. This paper describes the approach of the CCSDS SDLS working group to specify and execute the necessary interoperability tests. It first details the individual SDLS implementations that have been produced by ESA, NASA, and CNES and then the overall architecture that allows the interoperability tests between them. The paper reports on the results of the interoperability tests and identifies relevant aspects for the evolution of the test environment

Illness, normality and identity:the experience of heart transplant as a young adult

Purpose: End stage heart failure and transplant present great opportunities and challenges for patients of all ages. However, young adulthood may present additional specific challenges associated with the development of identity, career and romantic relationships. Despite recognition of greater mortality rates in young adults, consideration of the experience of transplant during this life stage has been largely overlooked in the literature. The aim of this study was to explore the experience of heart transplant in young adults. Method: Interviews were conducted with nine participants across three transplant services in the United Kingdom and the data subject to interpretative phenomenological analysis. Results: Analysis identified three themes. “Separating from illness” and “working toward normality” involved limiting the influence of illness on identity, as well as reengaging with typical functioning in young adulthood. “Integrating transplant into identity” involved acknowledging the influence of living with a shortened life expectancy. Conclusions: The need for support that recognizes specific challenges of transplant as a young adult is discussed (e.g. the development of age specific end of life pathways, improved communication between transplant recipients, their families and teams), including consideration of the impact of societal discourses (e.g. gift of life) which provided additional challenges for patients. IMPLICATIONS FOR REHABILITATION Heart transplant presents specific challenges according to the recipient’s life stage. The needs of young adult recipients should be considered. Transplant professionals should consider providing opportunities for peer support and addressing the identities and values of young adult transplant recipients during rehabilitation

The Relationship Between Alcohol Symptoms and Consumption Among Older Drinkers

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66310/1/j.1530-0277.1996.tb01104.x.pd

Low leakage-current InAsSb nanowire photodetectors on silicon

Axially doped p–i–n InAs0.93Sb0.07 nanowire arrays have been grown on Si substrates and fabricated into photodetectors for shortwave infrared detection. The devices exhibit a leakage current density around 2 mA/cm2 and a 20% cutoff of 2.3 μm at 300 K. This record low leakage current density for InAsSb based devices demonstrates the suitability of nanowires for the integration of III–V semiconductors with silicon technology