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Identification of host determinants of coronavirus infection informs mechanisms of viral pathogenesis and can provide new drug targets. Here we demonstrate that mammalian SWItch/Sucrose Non-Fermentable (mSWI/SNF) chromatin remodeling complexes, specifically canonical BRG1/BRM-associated factor (cBAF) complexes, promote severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and represent host-directed therapeutic targets. The catalytic activity of SMARCA4 is required for mSWI/SNF-driven chromatin accessibility at the ACE2 locus, ACE2 expression and virus susceptibility. The transcription factors HNF1A/B interact with and recruit mSWI/SNF complexes to ACE2 enhancers, which contain high HNF1A motif density. Notably, small-molecule mSWI/SNF ATPase inhibitors or degraders abrogate angiotensin-converting enzyme 2 (ACE2) expression and confer resistance to SARS-CoV-2 variants and a remdesivir-resistant virus in three cell lines and three primary human cell types, including airway epithelial cells, by up to 5 logs. These data highlight the role of mSWI/SNF complex activities in conferring SARS-CoV-2 susceptibility and identify a potential class of broad-acting antivirals to combat emerging coronaviruses and drug-resistant variants.

Several centrifuge and full-scale tests have demonstrated that an impression pile provides increased geotechnical capacity of up to 40% compared to a straight shafted pile depending on the quality of the indentations. The feasibility of creating indentations is governed by the strength of the clay, the capacity of the jack used in the impression tool, the impression shape and the area being impressed. Model tests and limit analyses have been carried out to optimise the impression tool. Results show that a flat-end or a flat-conical tip represents the best compromise between the need to reduce bearing capacity of the tip whilst maximising the indentation depth. Indentations must be spaced by at least 3 times their width to ensure a well-constructed impression pile with independent indentations.

Although successful COVID-19 vaccines have been developed, multiple pathogenic coronavirus species exist, urging for development of multi-species coronavirus vaccines. Here we developed prototype LNP-mRNA vaccine candidates against SARS-CoV-2 (Delta variant), SARS-CoV and MERS-CoV, and test how multiplexing of these LNP-mRNAs can induce effective immune responses in animal models. A triplex scheme of LNP-mRNA vaccination induced antigen-specific antibody responses against SARS-CoV-2, SARS-CoV and MERS-CoV, with a relatively weaker MERS-CoV response in this setting. Single cell RNA-seq profiled the global systemic immune repertoires and the respective transcriptome signatures of multiplexed vaccinated animals, which revealed a systemic increase in activated B cells, as well as differential gene expression signatures across major adaptive immune cells. Sequential vaccination showed potent antibody responses against all three species, significantly stronger than simultaneous vaccination in mixture. These data demonstrated the feasibility, antibody responses and single cell immune profiles of multi-species coronavirus vaccination. The direct comparison between simultaneous and sequential vaccination offers insights on optimization of vaccination schedules to provide broad and potent antibody immunity against three major pathogenic coronavirus species.One sentence summaryMultiplexed mRNA vaccination in simultaneous and sequential modes provide broad and potent immunity against pathogenic coronavirus species.

Immune responses to coronavirus disease 2019 (COVID-19) mRNA vaccines in primary antibody deficiencies (PADs) are largely unknown. We investigated antibody and CD4

Although COVID-19 vaccines have been developed, multiple pathogenic coronavirus species exist, urging on development of multispecies coronavirus vaccines. Here we develop prototype lipid nanoparticle (LNP)-mRNA vaccine candidates against SARS-CoV-2 Delta, SARS-CoV, and MERS-CoV, and we test how multiplexing LNP-mRNAs can induce effective immune responses in animal models. Triplex and duplex LNP-mRNA vaccinations induce antigen-specific antibody responses against SARS-CoV-2, SARS-CoV, and MERS-CoV. Single-cell RNA sequencing profiles the global systemic immune repertoires and respective transcriptome signatures of vaccinated animals, revealing a systemic increase in activated B cells and differential gene expression across major adaptive immune cells. Sequential vaccination shows potent antibody responses against all three species, significantly stronger than simultaneous vaccination in mixture. These data demonstrate the feasibility, antibody responses, and single-cell immune profiles of multispecies coronavirus vaccination. The direct comparison between simultaneous and sequential vaccination offers insights into optimization of vaccination schedules to provide broad and potent antibody immunity against three major pathogenic coronavirus species.

Infection of host cells by mammalian reovirus in culture or in tissues of infected animals results in cell death. Cell death of infected neurons and myocytes contributes to the pathogenesis of reovirus-induced encephalitis and myocarditis in a newborn mouse model. Thus, reovirus-induced cell death has been used to investigate the basis of viral disease. Depending on the cell type, infection of host cells by reovirus results in one of two forms of cell death-apoptosis and necroptosis. In addition to the obvious differences in how these two forms of cell death are executed, the mechanisms by which reovirus infection initiates and transduces signals that lead to each of these types of cell death are distinct. In this review, we discuss how apoptosis and necroptosis are triggered by events at different stages of infection. We also describe how innate immune recognition of reovirus genomic material and type I interferon signaling pathways connect with the core components of the apoptosis and necroptosis machinery. The impact of different cell death mediators on viral pathogenesis and the potential of reovirus as an oncolytic vector are also outlined.

As part of a project in collaboration with Lenovo’s Global UX team, we analyzed a website using heuristic analysis, a cognitive walkthrough, and feedback from users through verbal protocols. With this information, we created a prototype version of proposed content guidelines. These guidelines aim to improve consistency on the website, which allowed users to quickly compare multiple laptops as well as make connections between the laptop hardware and typical uses. In this paper, we describe our process behind developing these guidelines and the resulting guidelines themselves to show how researchers may develop their own guidelines.

The number of revision total knee arthroplasty procedures performed annually is increasing and, subsequently, so is the number of patients presenting following a failed revision. Rerevising a total knee arthroplasty after one or more failed revision procedures presents many challenges, including diminished bone stock for prosthetic fixation. "Off the shelf" implants may not offer the best alternative for reconstruction. We present the case of a 55-year-old patient who required a rerevision total knee arthroplasty following multiple failed revisions with severe femoral and tibia bone loss. We describe a novel technique we employed to improve component fixation within the compromised bone stock.

Ethical decisions in software development can substantially impact end-users, organizations, and our environment, as is evidenced by recent ethics scandals in the news. Organizations, like the ACM, publish codes of ethics to guide software-related ethical decisions. In fact, the ACM has recently demonstrated renewed interest in its code of ethics and made updates for the first time since 1992. To better understand how the ACM code of ethics changes software-related decisions, we replicated a prior behavioral ethics study with 63 software engineering students and 105 professional software developers, measuring their responses to 11 ethical vignettes. We found that explicitly instructing participants to consider the ACM code of ethics in their decision making had no observed effect when compared with a control group. Our findings suggest a challenge to the research community: if not a code of ethics, what techniques can improve ethical decision making in software engineering?

Alopecia areata is a form of non-scarring alopecia that results from a hyperactive immune response of T cells against hair follicles. Many patients with visible hair loss experience psychological and emotional distress, as a result of their cosmetic disfigurement, and frequently seek treatment. However, existing treatment methods, such as corticosteroids, topical irritants, sensitizing agents, immunosuppressants, and psoralen plus ultraviolet light A, may result in various adverse effects and often lack efficacy. Laser and light treatments offer a safe and effective alternative. This review aims to provide clinicians with a comprehensive summary of laser and light-based modalities used for the treatment of alopecia areata. Currently, the excimer laser is the most widely studied device and has shown positive results thus far. However, the development of future randomized controlled clinical trials will help determine the appropriate treatment protocols necessary, in order to achieve superior clinical outcomes.

Using a multi-country data set of over 600 survey participants, we show that psychographics and various attributes of the mobile app context are predictive of user privacy preferences. In particular, we find that a user's decision-making style is predictive of their privacy preferences, with users who are more independent decision makers tending to be more conservative about sharing personal information. We also provide additional insights into several of the privacy preference clusters identified in Lin et al.\@ 2014 by finding that users who are more privacy-concerned tend to be more knowledgeable of app privacy risks and more attentive to app permissions requests, and those individuals with less concern are more likely to trust well-known app companies.

Writer Jacques Ranciere speaks about the need for an a-disciplinary attitude while addressing contemporary art. He believes that medium specificity in aesthetic art is unnecessary, and discipline crossovers are crucial to create hybrid modern art.

The reliability of millimeter and sub-millimeter wave radiometer measurements is dependent on the accuracy of the loads they employ as calibration targets. In the recent past on-board calibration loads have been developed for a variety of satellite remote sensing instruments. Unfortunately some of these have suffered from calibration inaccuracies which had poor thermal performance of the calibration target as the root cause. Stringent performance parameters of the calibration target such as low reflectivity, high temperature uniformity, low mass and low power consumption combined with low volumetric requirements remain a challenge for the space instrument developer. In this paper we present a novel multi-layer absorber concept for a calibration load which offers an excellent compromise between very good radiometric performance and temperature uniformity and the mass and volumetric constraints required by space-borne calibration targets.

Recent experience of practice-led postgraduate supervision has prompted me to conclude that the practice-led research method, as it is currently construed, produces good outcomes, especially in permitting practitioners in the creative arts, design and media into the research framework, but at the same time it also generates certain recurring difficulties. What are these difficulties? Practice-led candidates tend to rely on a narrow range of formulations with the result that they assume: (i) the innovative nature of practice-led research; (ii) that its novelty is based in opposition to other research methods; (iii) that practice is intrinsically research, often leading to tautological formulations; and (iv) the hyper-self-reflexive nature of practice-led research. This paper proposes a set of guidelines composed in order to circumvent the shortcomings that result from these recurring formulations. My belief is that, if these shortcomings are avoided, there is nothing to prevent practice-led from further developing as a research inquiry and thus achieving rewarding and successful research outcomes. Originally composed for the purposes of postgraduate supervision, these six rules are presented here in the context of a wider analysis of the emergence of practice-led research and its current conditions of possibility as a research method.

The need for radiometer calibration targets with very low coherent backscatter (S11) is not fully appreciated in the community which designs and uses mm-wave radiometers. We discuss why very low S11 is required and our attempts to design make and test calibration target with such desired low backscatter for calibrating both ground and space-based radiometers.

Microwave radiometers are widely used for remote sensing and radio astronomical observations. Their absolute accuracy depends on the performance of the blackbody targets which are used for the radiometric calibration. In this paper we summarize the performance aspects of such calibration targets and present different designs for upcoming ESA missions.

(1994). The ‘Mess’ of Australian Art: The Necessity of Reading in Ian Burn's Historiography. Australian Journal of Art: Vol. 12, In Memoriam: Ian Burn, pp. 37-54.

The present study dissected the role of a Th2 bias in pathogenesis of Cryptococcus neoformans H99 infection by comparing inhalational H99 infections in wild-type BALB/c and IL-4/IL-13 double knockout mice. H99-infected wild-type mice showed all major hallmarks of Th2 but not Th1/Th17 immunity in the lungs and lung-associated lymph nodes. In contrast, the IL-4/13−/− mice developed robust hallmarks of Th1 and Th17 but not Th2 polarization. The IL-4/IL-13 deletion prevented pulmonary eosinophilia, goblet cell metaplasia in the airways and resulted in elevated serum IgE, and a switch from alternative to classical activation of macrophages. The development of a robust Th1/Th17 response and classical activation of macrophages resulted in significant containment of H99 in the lungs of IL-4/13−/− mice compared with unopposed growth of H99 in the lungs of wild-type mice. However, IL-4/13−/− mice showed only 1-week longer survival compared with wild-type mice. The comparison of brain and spleen cryptococcal loads at weeks 2, 3, and 4 postinfection revealed that the systemic dissemination in IL-4/13−/− mice occurred with an approximate 1-week delay but subsequently progressed with similar rate as in the wild-type mice. Furthermore, wild-type and IL-4/13−/− mice developed equivalently severe meningitis/encephalitis at the time of death. These data indicate that the Th2 immune bias is a crucial mechanism for pulmonary virulence of H99, whereas other mechanisms are largely responsible for its central nervous system tropism and systemic dissemination.

This paper intends to describe the integration of physical and numerical modelling, focusing on tunnels under seismic actions. It shows how numerical calculations can be used in association with centrifuge testing to model different aspects of tunnel behaviour during earthquakes. The scope of the paper has been limited to a few aspects, mainly concerning the change of internal forces in the tunnel lining during shaking and the effect of soil liquefaction. The interaction between a tunnel and a building in a soil layer undergoing liquefaction has also been taken into account.&nbsp