74 research outputs found

    Village Homes, Davis California: A Learning Lab for Future Planners

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    Built in the 1970s, Village Homes is an extremely successful housing development in Davis, California, and considered a model of sustainable community design. Energy-conscious houses are organized around a system of pedestrian-friendly streets and open spaces, with community facilities, shared gardens, orchards, and vineyards, all managed by residents. Professor Paul Wack, a founder of the Sustainable Environments minor in the College of Architecture and Environmental Design, has been adopting it as a case-study for his classes for several years

    Sustainability and Interdisciplinary Education: Planning and the CAED Sustainable Environments Program

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    For the past fifteen years, through an interdepartmental effort, the College of Architecture and Environmental Design has been offering an interdisciplinary minor on Sustainable Environments. CRP professor Paul Wack, a devoted co-founder and one of its most popular instructors, writes about this unique and popular initiative which recently received a national educational award from the American Institute of Architects

    Normalization in Supernatural deduction and in Deduction modulo

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    Deduction modulo and Supernatural deduction are two extentions of predicate logic with computation rules. Whereas the application of computation rules in deduction modulo is transparent, these rules are used to build non-logical deduction rules in Supernatural deduction. In both cases, adding computation rules may jeopardize proof normalization, but various conditions have been given in both cases, so that normalization is preserved. We prove in this paper that normalization in Supernatural deduction and in Deduction modulo are equivalent, i.e. the set of computation rules for which one system strongly normalizes is the same as the set of computation rules for which the other is

    A Serpin shapes the extracellular environment to prevent influenza A virus maturation

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    Interferon-stimulated genes (ISGs) act in concert to provide a tight barrier against viruses. Recent studies have shed light on the contribution of individual ISG effectors to the antiviral state, but most have examined those acting on early, intracellular stages of the viral life cycle. Here, we applied an image-based screen to identify ISGs inhibiting late stages of influenza A virus (IAV) infection. We unraveled a directly antiviral function for the gene SERPINE1, encoding plasminogen activator inhibitor 1 (PAI-1). By targeting extracellular airway proteases, PAI-1 inhibits IAV glycoprotein cleavage, thereby reducing infectivity of progeny viruses. This was biologically relevant for IAV restriction in vivo. Further, partial PAI-1 deficiency, attributable to a polymorphism in human SERPINE1, conferred increased susceptibility to IAV in vitro. Together, our findings reveal that manipulating the extracellular environment to inhibit the last step in a virus life cycle is an important mechanism of the antiviral response

    Type I interferons drive MAIT cell functions against bacterial pneumonia

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    Mucosal-associated invariant T (MAIT) cells are abundant in the lung and contribute to host defense against infections. During bacterial infections, MAIT cell activation has been proposed to require T cell receptor (TCR)–mediated recognition of antigens derived from the riboflavin synthesis pathway presented by the antigen-presenting molecule MR1. MAIT cells can also be activated by cytokines in an MR1-independent manner, yet the contribution of MR1-dependent vs. -independent signals to MAIT cell functions in vivo remains unclear. Here, we use Klebsiella pneumoniae as a model of bacterial pneumonia and demonstrate that MAIT cell activation is independent of MR1 and primarily driven by type I interferons (IFNs). During Klebsiella infection, type I IFNs stimulate activation of murine and human MAIT cells, induce a Th1/cytotoxic transcriptional program, and modulate MAIT cell location within the lungs. Consequently, adoptive transfer or boosting of pulmonary MAIT cells protect mice from Klebsiella infection, with protection being dependent on direct type I IFN signaling on MAIT cells. These findings reveal type I IFNs as new molecular targets to manipulate MAIT cell functions during bacterial infections

    A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

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    The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

    Both “illness and temptation of the enemy”: melancholy, the medieval patient and the writings of King Duarte of Portugal (r. 1433–38)

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    Recent historians have rehabilitated King Duarte of Portugal, previously maligned and neglected, as an astute ruler and philosopher. There is still a tendency, however, to view Duarte as a depressive or a hypochondriac, due to his own description of his melancholy in his advice book, the Loyal Counselor. This paper reassesses Duarte's writings, drawing on key approaches in the history of medicine, such as narrative medicine and the history of the patient. It is important to take Duarte's views on his condition seriously, placing them in the medical and theological contexts of his time and avoiding modern retrospective diagnosis. Duarte's writings can be used to explore the impact of plague, doubt and death on the life of a well-educated and conscientious late-medieval ruler
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