Control vs. Care: Frameworks for Systems Redesign During COVID-19

This workshop will use Zoom Breakout rooms and a shared Miro board as a space for visual collaboration. A simple orientation will be provided. That said, folks who are not able to simultaneously connect to or operate the Miro board will still be able to participate fully. PURPOSE The scale and urgency of the Covid-19 pandemic have strained social systems both locally and globally, warranting a spirit of creative resourcefulness in tending to the crisis while new specially-tailored systems are conceived. In the face of this challenge, a jarring clash often occurs as socio-technical systems, with their pre-existing design priorities, simply reposition their services in response to the new demands of a public health emergency. As communities struggle to resume work, education, and entertainment, a persistent design question lies at the centre: what should we be optimizing for in this new context, and how might the values of our available systems support or hinder that aim? This design challenge finds an important design ally in Bioethics, which helpfully introduces comparative frameworks of Control and Care drawn from the practice of health and medicine. These distinctions are extensible to the assessment and reimagining of non-medical socio-technical systems. In this workshop, we’ll examine a variety of systems we observe in this situation, introduce the history and principles of these frameworks, and operationalize them as Design tools. So-called “smart access” systems are one such example of an existing system being repurposed in response to Covid-19. These products, previously marketed as “automated, contactless property management solutions,” are now touted as a means to secure the acute health and safety concerns of a building’s occupants. These systems are visible throughout commercial buildings, often connecting peripherals such as thermal scanners, biometric readers, mask-detection cameras, and human security attendants. When observed through the framework of Control, core attributes of the existing system design emerge: an architectural paradigm of “compatibility,” a single-direction data authority structure, and a broad subjugation of human users without mechanisms to declare consent. Reframing the design analysis through the framework of Care reveals the system’s centering on asset security priorities at the expense of the dynamic social environment it is purported to support. The framework of Care also reveals alternative priorities, such as the privacy and well-being interests of people that encounter the building, or a notion of community maintenance rather than an attitude of surveillance. This designerly approach to comparative analysis also provides a foundation to inspire forward-looking systems thinking and design. In the case of “smart access,” how might these systems better sense and support the health and safety needs of the surrounding community? By leveraging the frameworks, value-driven design responses emerge, such as disclosing readings only to the assessed person, automating targeted maintenance services, and including local health authorities as participant stakeholders of the system. Stepping back from the present context of Covid-19, we can ask how these insights might fundamentally change the design of systems to contribute more responsibly to sustainable and equitable societies. RSD9 THEMES Systemic thinking for creating products, services and systems for contentment and sustainability Systems for equity, collectivism, co-design and citizen movements Methodology, philosophy and theory of systemic design WORKSHOP GOALS & EXPECTED OUTCOMES The goals of this workshop are to: Introduce system-value alignments in context, Translate Bioethics frameworks of Control and Care to frameworks of systems thinking Identify opportunities to enhance the practical methodologies of systems design to centre on the sustainable well-being of individuals and society. Through this workshop, we expect to: Generate a collection of example cases (including initial comparative analyses through the frameworks of Control and Care, as well as sketches of imagined alternatives) Refine a translational framework of systems of control versus systems of care to share with the greater RSD and System Design community WORKSHOP STRUCTURE The following outline is for a 90-minute workshop: Opening Activity [10m] The opening exercise will ask participants to think of systems that are currently responding to Covid-19 demands but were originally conceived for vastly different purposes. We’ll discuss some of these examples as a group. Introduction of Frameworks [15m] The facilitators will introduce Bioethics frameworks of Control and Care, providing an overview of relevant principles as well as historical examples of their translation to practice. Story-sharing & Intention Setting [25m] Participants and facilitators will share their own perspectives and experiences with systems of Control and of Care, both as designers and as people experiencing the systems’ effects. We will begin compiling ideas about essential attributes, priorities, and interests within these systems. Systems Analysis & Re-imagining [25m] Participants will select one system for comparative design analysis—first through the lens of Control, then through the lens of Care—then imagine responsible design alternatives. A prompt for re-imagining might be: In a post-COVID context, how might these systems better support systems for equity, collectivism, and flourishing ecological systems? Gallery & Closing Reflection [15m] Participants will share their work with the full group, reflect on what we learned in the process, and consider avenues for developing resources for professional and pedagogical communities

Conformational activation of ADAMTS13

A disintegrin and metalloprotease with thrombospondin motifs 13 (ADAMTS13) is a metalloprotease that regulates von Willebrand factor (VWF) function. ADAMTS13-mediated proteolysis is determined by conformational changes in VWF, but also may depend on its own conformational activation. Kinetic analysis of WT ADAMTS13 revealed ∼2.5-fold reduced activity compared with ADAMTS13 lacking its C-terminal tail (MDTCS) or its CUB1-2 domains (WTΔCUB1-2), suggesting that the CUB domains naturally limit ADAMTS13 function. Consistent with this suggestion, WT ADAMTS13 activity was enhanced ∼2.5-fold by preincubation with either an anti-CUB mAb (20E9) or VWF D4CK (the natural binding partner for the CUB domains). Furthermore, the isolated CUB1-2 domains not only bound MDTCS, but also inhibited activity by up to 2.5-fold. Interestingly, a gain-of-function (GoF) ADAMTS13 spacer domain variant (R568K/F592Y/R660K/Y661F/Y665F) was ∼2.5-fold more active than WT ADAMTS13, but could not be further activated by 20E9 mAb or VWF D4CK and was unable to bind or to be inhibited by the CUB1-2 domains, suggesting that the inhibitory effects of the CUB domains involve an interaction with the spacer domain that is disrupted in GoF ADAMTS13. Electron microscopy demonstrated a “closed” conformation of WT ADAMTS13 and suggested a more “open” conformation for GoF ADAMTS13. The cryptic spacer domain epitope revealed by conformational unfolding also represents the core antigenic target for autoantibodies in thrombotic thrombocytopenic purpura. We propose that ADAMTS13 circulates in a closed conformation, which is maintained by a CUB–spacer domain binding interaction. ADAMTS13 becomes conformationally activated on demand through interaction of its C-terminal CUB domains with VWF, making it susceptible to immune recognition

A Comparison of Photometric Redshift Techniques for Large Radio Surveys

Future radio surveys will generate catalogs of tens of millions of radio sources, for which redshift estimates will be essential to achieve many of the science goals. However, spectroscopic data will be available for only a small fraction of these sources, and in most cases even the optical and infrared photometry will be of limited quality. Furthermore, radio sources tend to be at higher redshift than most optical sources (most radio surveys have a median redshift greater than 1) and so a significant fraction of radio sources hosts differ from those for which most photometric redshift templates are designed. We therefore need to develop new techniques for estimating the redshifts of radio sources. As a starting point in this process, we evaluate a number of machine-learning techniques for estimating redshift, together with a conventional template-fitting technique. We pay special attention to how the performance is affected by the incompleteness of the training sample and by sparseness of the parameter space or by limited availability of ancillary multiwavelength data. As expected, we find that the quality of the photometric-redshift degrades as the quality of the photometry decreases, but that even with the limited quality of photometry available for all-sky-surveys, useful redshift information is available for the majority of sources, particularly at low redshift. We find that a template-fitting technique performs best in the presence of high-quality and almost complete multi-band photometry, especially if radio sources that are also X-ray emitting are treated separately, using specific templates and priors. When we reduced the quality of photometry to match that available for the EMU all-sky radio survey, the quality of the template-fitting degraded and became comparable to some of the machine-learning methods. Machine learning techniques currently perform better at low redshift than at high redshift, because of incompleteness of the currently available training data at high redshifts

A comparison of photometric redshift techniques for large radio surveys

Future radio surveys will generate catalogs of tens of millions of radio sources, for which redshift estimates will be essential to achieve many of the science goals. However, spectroscopic data will be available for only a small fraction of these sources, and in most cases even the optical and infrared photometry will be of limited quality. Furthermore, radio sources tend to be at higher redshift than most optical sources (most radio surveys have a median redshift greater than 1) and so a significant fraction of radio sources hosts differ from those for which most photometric redshift templates are designed. We therefore need to develop new techniques for estimating the redshifts of radio sources. As a starting point in this process, we evaluate a number of machine-learning techniques for estimating redshift, together with a conventional template-fitting technique. We pay special attention to how the performance is affected by the incompleteness of the training sample and by sparseness of the parameter space or by limited availability of ancillary multiwavelength data. As expected, we find that the quality of the photometric-redshift degrades as the quality of the photometry decreases, but that even with the limited quality of photometry available for all-sky-surveys, useful redshift information is available for the majority of sources, particularly at low redshift. We find that a template-fitting technique performs best in the presence of high-quality and almost complete multi-band photometry, especially if radio sources that are also X-ray emitting are treated separately, using specific templates and priors. When we reduced the quality of photometry to match that available for the EMU all-sky radio survey, the quality of the template-fitting degraded and became comparable to some of the machine-learning methods. Machine learning techniques currently perform better at low redshift than at high redshift, because of incompleteness of the currently available training data at high redshifts

The damage-associated molecular pattern HMGB1 is released early after clinical hepatic ischemia/reperfusion.

OBJECTIVE AND BACKGROUND: Activation of sterile inflammation after hepatic ischemia/reperfusion (I/R) culminates in liver injury. The route to liver damage starts with mitochondrial oxidative stress and cell death during early reperfusion. The link between mitochondrial oxidative stress, damage-associate molecular pattern (DAMP) release, and sterile immune signaling is incompletely understood and lacks clinical validation. The aim of the study was to validate this relation in a clinical liver I/R cohort and to limit DAMP release using a mitochondria-targeted antioxidant in I/R-subjected mice. METHODS: Plasma levels of the DAMPs high-mobility group box 1 (HMGB1), mitochondrial DNA, and nucleosomes were measured in 39 patients enrolled in an observational study who underwent a major liver resection with (N = 29) or without (N = 13) intraoperative liver ischemia. Circulating cytokine and neutrophil activation markers were also determined. In mice, the mitochondria-targeted antioxidant MitoQ was intravenously infused in an attempt to limit DAMP release, reduce sterile inflammation, and suppress I/R injury. RESULTS: In patients, HMGB1 was elevated following liver resection with I/R compared to liver resection without I/R. HMGB1 levels correlated positively with ischemia duration and peak post-operative transaminase (ALT) levels. There were no differences in mitochondrial DNA, nucleosome, or cytokine levels between the two groups. In mice, MitoQ neutralized hepatic oxidative stress and decreased HMGB1 release by ±50%. MitoQ suppressed transaminase release, hepatocellular necrosis, and cytokine production. Reconstituting disulfide HMGB1 during reperfusion reversed these protective effects. CONCLUSION: HMGB1 seems the most pertinent DAMP in clinical hepatic I/R injury. Neutralizing mitochondrial oxidative stress may limit DAMP release after hepatic I/R and reduce liver damage

MeerKAT uncovers the physics of an odd radio circle

Odd radio circles (ORCs) are recently-discovered faint diffuse circles of radio emission, of unknown cause, surrounding galaxies at moderate redshift (z ∼0.2-0.6). Here, we present detailed new MeerKAT radio images at 1284 MHz of the first ORC, originally discovered with the Australian Square Kilometre Array Pathfinder, with higher resolution (6 arcsec) and sensitivity (∼2.4 μJy/beam). In addition to the new images, which reveal a complex internal structure consisting of multiple arcs, we also present polarization and spectral index maps. Based on these new data, we consider potential mechanisms that may generate the ORCs

The MeerKAT 1.3 GHz Survey of the Small Magellanic Cloud

We present new radio continuum images and a source catalogue from the MeerKAT survey in the direction of the Small Magellanic Cloud (SMC). The observations, at a central frequency of 1.3 GHz across a bandwidth of 0.8 GHz, encompass a field of view ~7 x 7 degrees and result in images with resolution of 8 arcsec. The median broad-band Stokes I image Root Mean Squared noise value is ~11 microJy/beam. The catalogue produced from these images contains 108,330 point sources and 517 compact extended sources. We also describe a UHF (544-1088 MHz) single pointing observation. We report the detection of a new confirmed Supernova Remnant (SNR) (MCSNR J0100-7211) with an X-ray magnetar at its centre and 10 new SNR candidates. This is in addition to the detection of 21 previously confirmed SNRs and two previously noted SNR candidates. Our new SNR candidates have typical surface brightness an order of magnitude below those previously known, and on the whole they are larger. The high sensitivity of the MeerKAT survey also enabled us to detect the bright end of the SMC Planetary Nebulae (PNe) sample - point-like radio emission is associated with 38 of 102 optically known PNe, of which 19 are new detections. Lastly, we present the detection of three foreground radio stars amidst 11 circularly polarised sources, and a few examples of morphologically interesting background radio galaxies from which the radio ring galaxy ESO 029-G034 may represent a new type of radio object

Autoregulation of von Willebrand factor function by a disulfide bond switch

Force-dependent binding of platelet glycoprotein Ib (GPIb) receptors to plasma von Willebrand factor (VWF) plays a key role in hemostasis and thrombosis. Previous studies have suggested that VWF activation requires force-induced exposure of the GPIb binding site in the A1 domain that is autoinhibited by the neighboring A2 domain. However, the biochemical basis of this “mechanopresentation” remains elusive. From a combination of protein chemical, biophysical, and functional studies, we find that the autoinhibition is controlled by the redox state of an unusual disulfide bond near the carboxyl terminus of the A2 domain that links adjacent cysteine residues to form an eight-membered ring. Only when the bond is cleaved does the A2 domain bind to the A1 domain and block platelet GPIb binding. Molecular dynamics simulations indicate that cleavage of the disulfide bond modifies the structure and molecular stresses of the A2 domain in a long-range allosteric manner, which provides a structural explanation for redox control of the autoinhibition. Significantly, the A2 disulfide bond is cleaved in ~75% of VWF subunits in healthy human donor plasma but in just ~25% of plasma VWF subunits from heart failure patients who have received extracorporeal membrane oxygenation support. This suggests that the majority of plasma VWF binding sites for platelet GPIb are autoinhibited in healthy donors but are mostly available in heart failure patients. These findings demonstrate that a disulfide bond switch regulates mechanopresentation of VWF.: This study was supported by grants from the National Health and Medical Research Council of Australia (P.J.H.), Royal College of Pathologists Foundation Kanematsu/Novo Nordisk Research Award (F.P. and L.J.), Diabetes Australia Research Trust grant G179720 and Sydney Medical School Early-Career Researcher Kickstart Grant (L.J.), National Heart Foundation of Australia Postdoctoral Fellowship (101285) (L.J.) and British Heart Foundation Intermediate Basic Science Research Fellowship (FS/11/51/28920) (B.M.L.), Deutsche Forschungsgemeinschaft (research unit FOR 1543 to C.A.-S., C.B., and F.G.), the Center for Modelling and Simulation in the Biosciences postdoctoral program of the Heidelberg University (A.B.), and the Klaus Tschira Foundation (F.G.). B.L. was supported by the Dutch Thrombosis Foundation through grant number 2016-03.