Increased antigen specific T cell numbers in the absence of altered migration or division rates as a result of mucosal cholera toxin administration

Cholera toxin (CT) is a mucosal adjuvant capable of inducing strong immune responses to co-administered antigens following oral or intranasal immunization of mice. To date, the direct effect of CT on antigen-specific CD4(+) T cell migration and proliferation profiles in vivo is not well characterized. In this study, the effect of CT on the migration pattern and proliferative responses of adoptively transferred, CD4(+) TCR transgenic T cells in orally or intranasally vaccinated mice, was analyzed by flow cytometry. GFP-expressing or CFSE-labeled OT-II lymphocytes were adoptively transferred to naïve C57BL/6 mice, and mice were subsequently vaccinated with OVA with or without CT via the oral or intranasal route. CT did not alter the migration pattern of antigen-specific T cells, regardless of the route of immunization, but increased the number of transgenic CD4(+) T cells in draining lymphoid tissue. This increase in the number of transgenic CD4(+) T cells was not due to cells undergoing more rounds of cellular division in vivo, suggesting that CT may exert an indirect adjuvant effect on CD4(+) T cells. The findings reported here suggest that CT functions as a mucosal adjuvant by increasing the number of antigen specific CD4(+) T cells independent of their migration pattern or kinetics of cellular division.Grant support was received from the National Health and Medical Research Council of Australia (NHMRC). OLW is a recipient of an R.D. Wright Career Development Award

Age-related changes in afferent pathways and urothelial function in the male mouse bladder

Key points •The prevalence of bladder conditions such as overactive bladder syndrome and urinary incontinence significantly increases with age, but how bladder function is altered by ageing is unclear. •Sensory nerves together with the epithelial lining of the bladder known as the urothelium play a key role in mediating bladder function. •In aged male mice we find a significant increase in natural bladder voiding, augmented afferent nerve firing during bladder filling and a significant increase in urothelial responses to purinergic receptor stimulation. •This suggests that with ageing there is increased purinergic transmission in the mouse bladder which may lead to increased sensation and result in bladder hypersensitivity. •These findings help us better understand how the function of the bladder may be affected by advancing age. Abstract The prevalence of lower urinary tract storage disorders such as overactive bladder syndrome and urinary incontinence significantly increase with age. Previous studies have demonstrated age-related changes in detrusor function and urothelial transmitter release but few studies have investigated how the urothelium and sensory pathways are affected. The aim of this study was to investigate the effect of ageing on urothelial-afferent signalling in the mouse bladder. Three-month-old control and 24-month-old aged male mice were used. In vivo natural voiding behaviour, sensory nerve activity, urothelial cell function, muscle contractility, transmitter release and gene and protein expression were measured to identify how all three components of the bladder (neural, contractile and urothelial) are affected by ageing. In aged mice, increased voiding frequency and enhanced low threshold afferent nerve activity was observed, suggesting that ageing induces overactivity and hypersensitivity of the bladder. These changes were concurrent with altered ATP and acetylcholine bioavailability, measured as transmitter overflow into the lumen, increased purinergic receptor sensitivity and raised P2X3 receptor expression in the urothelium. Taken together, these data suggest that ageing results in aberrant urothelial function, increased afferent mechanosensitivity, increased smooth muscle contractility, and changes in gene and protein expression (including of P2X3). These data are consistent with the hypothesis that ageing evokes changes in purinergic signalling from the bladder, and further studies are now required to fully validate this idea

Anti-C1q Autoantibodies Are Frequently Detected in Patients With Systemic Sclerosis Associated With Pulmonary Fibrosis

BACKGROUND: Anti-C1q autoantibodies (autoAbs) are associated with systemic lupus erythematosus (SLE) but their presence in other rheumatic diseases has not been adequately investigated. OBJECTIVE: We aim to assessanti-C1q autoAbs and circulating immune complexes (CICs) in systemic sclerosis (SSc). METHODS: One hundred twenty four patients with SSc (106 females; median age 59.4 years, range 25-81.4; 75(60.5%) with limited cutaneous SSc[lcSSc], and 49(39.5%) with diffuse cutaneous SSc[dcSSc]), were studied. Twenty-five patients with Sjögren\u27s syndrome (SjS), 29 with rheumatoid arthritis (RA), and 38 patients with systemic lupus erythematosus (SLE) and 53 healthy controls (NC) were also included. ELISAs with high and low salt buffers the former allowing IgGFc binding to C1q, the latter not allowing IgGFc binding and anti-C1q Ab binding to C1q were used to measure anti-C1q Abs and CICs. RESULTS: Anti-C1q Abs were present in20/124 (16.1%) SSc patients [5 had high levels (\u3e80 RU/mL) and 10 patients (50%) had moderate levels (40-80 RU/mL)] compared to 1/25 (4%) SjS, 1/29 (3.4%) RA patients (p CONCLUSIONS: Anti-C1q autoAbs were frequently detected in patients with SSc and their high levels predict the co-occurrence of pulmonary fibrosis or pulmonary arterial hypertension

Multi-functional metasurface architecture for amplitude, polarization and wavefront control

Metasurfaces (MSs) have been utilized to manipulate different properties of electromagnetic waves. By combining local control over the wave amplitude, phase, and polarization into a single tunable structure, a multi-functional and reconfigurable metasurface can be realized, capable of full control over incident radiation. Here, we experimentally validate a multi-functional metasurface architecture for the microwave regime, where in principle variable loads are connected behind the backplane to reconfigurably shape the complex surface impedance. As a proof-of-concept step, we fabricate several metasurface instances with static loads in different configurations (surface mount capacitors and resistors of different values in different connection topologies) to validate the approach and showcase the different achievable functionalities. Specifically, we show perfect absorption for oblique incidence (both polarizations), broadband linear polarization conversion, and beam splitting, demonstrating control over the amplitude, polarization state, and wavefront, respectively. Measurements are performed in the 4-18 GHz range inside an anechoic chamber and show good agreement with theoretically-anticipated results. Our results clearly demonstrate the practical potential of the proposed architecture for reconfigurable electromagnetic wave manipulation.Comment: 6 pages, 5 figure

From social machines to social protocols:Software engineering foundations for sociotechnical systems

The overarching vision of social machines is to facilitate social processes by having computers provide administrative support. We conceive of a social machine as a sociotechnical system (STS): a software-supported system in which autonomous principals such as humans and organizations interact to exchange information and services. Existing approaches for social machines emphasize the technical aspects and inadequately support the meanings of social processes, leaving them informally realized in human interactions. We posit that a fundamental rethinking is needed to incorporate accountability, essential for addressing the openness of the Web and the autonomy of its principals. We introduce Interaction-Oriented Software Engineering (IOSE) as a paradigm expressly suited to capturing the social basis of STSs. Motivated by promoting openness and autonomy, IOSE focuses not on implementation but on social protocols, specifying how social relationships, characterizing the accountability of the concerned parties, progress as they interact. Motivated by providing computational support, IOSE adopts the accountability representation to capture the meaning of a social machine’s states and transitions. We demonstrate IOSE via examples drawn from healthcare. We reinterpret the classical software engineering (SE) principles for the STS setting and show how IOSE is better suited than traditional software engineering for supporting social processes. The contribution of this paper is a new paradigm for STSs, evaluated via conceptual analysis

ABSense: Sensing Electromagnetic Waves on Metasurfaces via Ambient Compilation of Full Absorption

Metasurfaces constitute effective media for manipulating and transforming impinging EM waves. Related studies have explored a series of impactful MS capabilities and applications in sectors such as wireless communications, medical imaging and energy harvesting. A key-gap in the existing body of work is that the attributes of the EM waves to-be-controlled (e.g., direction, polarity, phase) are known in advance. The present work proposes a practical solution to the EM wave sensing problem using the intelligent and networked MS counterparts-the HyperSurfaces (HSFs), without requiring dedicated field sensors. An nano-network embedded within the HSF iterates over the possible MS configurations, finding the one that fully absorbs the impinging EM wave, hence maximizing the energy distribution within the HSF. Using a distributed consensus approach, the nano-network then matches the found configuration to the most probable EM wave traits, via a static lookup table that can be created during the HSF manufacturing. Realistic simulations demonstrate the potential of the proposed scheme. Moreover, we show that the proposed workflow is the first-of-its-kind embedded EM compiler, i.e., an autonomic HSF that can translate high-level EM behavior objectives to the corresponding, low-level EM actuation commands.Comment: Publication: Proceedings of ACM NANOCOM 2019. This work was funded by the European Union via the Horizon 2020: Future Emerging Topics call (FETOPEN), grant EU736876, project VISORSURF (http://www.visorsurf.eu

XR-RF Imaging Enabled by Software-Defined Metasurfaces and Machine Learning: Foundational Vision, Technologies and Challenges

We present a new approach to Extended Reality (XR), denoted as iCOPYWAVES, which seeks to offer naturally low-latency operation and cost-effectiveness, overcoming the critical scalability issues faced by existing solutions. iCOPYWAVES is enabled by emerging PWEs, a recently proposed technology in wireless communications. Empowered by intelligent (meta)surfaces, PWEs transform the wave propagation phenomenon into a software-defined process. We leverage PWEs to i) create, and then ii) selectively copy the scattered RF wavefront of an object from one location in space to another, where a machine learning module, accelerated by FPGAs, translates it to visual input for an XR headset using PWEdriven, RF imaging principles (XR-RF). This makes for an XR system whose operation is bounded in the physical layer and, hence, has the prospects for minimal end-to-end latency. Over large distances, RF-to-fiber/fiber-to-RF is employed to provide intermediate connectivity. The paper provides a tutorial on the iCOPYWAVES system architecture and workflow. A proof-of-concept implementation via simulations is provided, demonstrating the reconstruction of challenging objects in iCOPYWAVES produced computer graphics