853 research outputs found

    Navigating Uncertainty: The Future of Futures Analysis in the Australian Public Service

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    Balancing Prediction and Sensory Input in Speech Comprehension: The Spatiotemporal Dynamics of Word Recognition in Context.

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    Spoken word recognition in context is remarkably fast and accurate, with recognition times of ∼200 ms, typically well before the end of the word. The neurocomputational mechanisms underlying these contextual effects are still poorly understood. This study combines source-localized electroencephalographic and magnetoencephalographic (EMEG) measures of real-time brain activity with multivariate representational similarity analysis to determine directly the timing and computational content of the processes evoked as spoken words are heard in context, and to evaluate the respective roles of bottom-up and predictive processing mechanisms in the integration of sensory and contextual constraints. Male and female human participants heard simple (modifier-noun) English phrases that varied in the degree of semantic constraint that the modifier (W1) exerted on the noun (W2), as in pairs, such as "yellow banana." We used gating tasks to generate estimates of the probabilistic predictions generated by these constraints as well as measures of their interaction with the bottom-up perceptual input for W2. Representation similarity analysis models of these measures were tested against electroencephalographic and magnetoencephalographic brain data across a bilateral fronto-temporo-parietal language network. Consistent with probabilistic predictive processing accounts, we found early activation of semantic constraints in frontal cortex (LBA45) as W1 was heard. The effects of these constraints (at 100 ms after W2 onset in left middle temporal gyrus and at 140 ms in left Heschl's gyrus) were only detectable, however, after the initial phonemes of W2 had been heard. Within an overall predictive processing framework, bottom-up sensory inputs are still required to achieve early and robust spoken word recognition in context.SIGNIFICANCE STATEMENT Human listeners recognize spoken words in natural speech contexts with remarkable speed and accuracy, often identifying a word well before all of it has been heard. In this study, we investigate the brain systems that support this important capacity, using neuroimaging techniques that can track real-time brain activity during speech comprehension. This makes it possible to locate the brain areas that generate predictions about upcoming words and to show how these expectations are integrated with the evidence provided by the speech being heard. We use the timing and localization of these effects to provide the most specific account to date of how the brain achieves an optimal balance between prediction and sensory input in the interpretation of spoken language

    Design considerations for the bottom cell in perovskite/silicon tandems: a terawatt scalability perspective

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    Perovskite/silicon tandems have smashed through the 30% efficiency barrier, which represents a promising step towards high efficiency solar modules. However, the processing used to fabricate high efficiency devices is not compatible with mass production. For this technology to be impactful in the urgent fight against climate change and be scalable to the multi-terawatt (TW) level, a shift in mindset is required when designing the silicon bottom cell. In this work, we outline the design requirements for the silicon cell, with a particular focus on the constraints imposed by industrial processing. In doing so, we discuss the type of silicon wafers used, the surface treatment, the most appropriate silicon cell architecture and the formation of metal contacts. Additionally, we frame this discussion in the context of multi-TW markets, which impose additional constraints on the processing relating to the sustainability of the materials used. The discussion herein will help to shape the design of future silicon solar cells for use in tandems, so that the LCOE of solar electricity can be driven to new lows

    Understory 2014

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    “Art is the struggle to be, in a particular sort of way, virtuous.” —Iris Murdoch Indeed, when we embark on any creative adventure it is with the purpose of conveying a certain truth; an emotion, an idea that brings us together and reminds us of the innate consciousness that dwells within. Understory is emblematic of this; where individuals intent on honing their craft can join others to become a part of something greater, their work immortalized to become a time capsule. Decades from now a volume of Understory may be discovered on a dusty bookshelf in some forgotten corner and the lucky explorer who finds it shall be enlightened by pages of gold. We, as editors of Understory 2014, have worked very hard this year to put together a journal that showcases the very best of the University of Alaska Anchorage undergraduate student work. We hope you enjoy your journey through this issue as much as we have enjoyed ours. Thank you to the English and Art Departments, for the staff and faculty’s unerring support of our club; to Provost Baker, for seeing and believing in the vision of Understory; and to our club’s faculty advisor, Douglass Bourne, for his guidance and tireless assistance. Finally, thank you to the wonderful students who submit such excellent work each year. Without your passion for the arts, we would not be here.Staff / Letter from the Editors / Glass Blower / Writing / Obsolete Evolution / Permafrost / Phoenix / Untitled / Ratio / Tripping / Abiogenesis / My Heart Beats for You / Meeting of the Fingerprint Lines / You Are No Stranger / Nightmare Fuel / Cane-Sugar / Gossamer Strands / Panthera Gold / Butterfly / A Mantis Too Far / Long and Winding Road / Chasing Shadows / Merisunas / Chequer Grove / Modzilla / Beans / Little Red and Mr. Wolf / In Memoriam, Joel Fletcher Armstrong / Glance / Courage / Uranium Waltz / Danger / Journey to the West / Antumbra / Roaring Like a Lion / Pre-boarding / Untitled / How Do You Say a Word / Fishing for Doom/ Contributor

    Non-parametric Heat Map Representation of Flow Cytometry Data: Identifying Cellular Changes Associated With Genetic Immunodeficiency Disorders

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    Genetic primary immunodeficiency diseases are increasingly recognized, with pathogenic mutations changing the composition of circulating leukocyte subsets measured by flow cytometry (FCM). Discerning changes in multiple subpopulations is challenging, and subtle trends might be missed if traditional reference ranges derived from a control population are applied. We developed an algorithm where centiles were allocated using non-parametric comparison to controls, generating multiparameter heat maps to simultaneously represent all leukocyte subpopulations for inspection of trends within a cohort or segregation with a putative genetic mutation. To illustrate this method, we analyzed patients with Primary Antibody Deficiency (PAD) and kindreds harboring mutations in TNFRSF13B (encoding TACI), CTLA4, and CARD11. In PAD, loss of switched memory B cells (B-SM) was readily demonstrated, but as a continuous, not dichotomous, variable. Expansion of CXCR5+/CD45RA- CD4+ T cells (X5-Th cells) was a prominent feature in PAD, particularly in TACI mutants, and patients with expansion in CD21-lo B cells or transitional B cells were readily apparent. We observed differences between unaffected and affected TACI mutants (increased B cells and CD8+ T-effector memory cells, loss of B-SM cells and non-classical monocytes), cellular signatures that distinguished CTLA4 haploinsufficiency itself (expansion of plasmablasts, activated CD4+ T cells, regulatory T cells, and X5-Th cells) from its clinical expression (B-cell depletion), and those that were associated with CARD11 gain-of-function mutation (decreased CD8+ T effector memory cells, B cells, CD21-lo B cells, B-SM cells, and NK cells). Co-efficients of variation exceeded 30% for 36/54 FCM parameters, but by comparing inter-assay variation with disease-related variation, we ranked each parameter in terms of laboratory precision vs. disease variability, identifying X5-Th cells (and derivatives), naïve, activated, and central memory CD8+ T cells, transitional B cells, memory and SM-B cells, plasmablasts, activated CD4 cells, and total T cells as the 10 most useful cellular parameters. Applying these to cluster analysis of our PAD cohort, we could detect subgroups with the potential to reflect underlying genotypes. Heat mapping of normalized FCM data reveals cellular trends missed by standard reference ranges, identifies changes associating with a phenotype or genotype, and could inform hypotheses regarding pathogenesis of genetic immunodeficiency.This study was supported by a National Health and Medical Research Council (NHMRC) of Australia Centre of Research Excellence (APP1079648)

    On Specifying for Trustworthiness

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    As autonomous systems (AS) increasingly become part of our daily lives, ensuring their trustworthiness is crucial. In order to demonstrate the trustworthiness of an AS, we first need to specify what is required for an AS to be considered trustworthy. This roadmap paper identifies key challenges for specifying for trustworthiness in AS, as identified during the "Specifying for Trustworthiness" workshop held as part of the UK Research and Innovation (UKRI) Trustworthy Autonomous Systems (TAS) programme. We look across a range of AS domains with consideration of the resilience, trust, functionality, verifiability, security, and governance and regulation of AS and identify some of the key specification challenges in these domains. We then highlight the intellectual challenges that are involved with specifying for trustworthiness in AS that cut across domains and are exacerbated by the inherent uncertainty involved with the environments in which AS need to operate.Comment: Accepted version of paper. 13 pages, 1 table, 1 figur

    Human α2β1HI CD133+VE epithelial prostate stem cells express low levels of active androgen receptor

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    Stem cells are thought to be the cell of origin in malignant transformation in many tissues, but their role in human prostate carcinogenesis continues to be debated. One of the conflicts with this model is that cancer stem cells have been described to lack androgen receptor (AR) expression, which is of established importance in prostate cancer initiation and progression. We re-examined the expression patterns of AR within adult prostate epithelial differentiation using an optimised sensitive and specific approach examining transcript, protein and AR regulated gene expression. Highly enriched populations were isolated consisting of stem (α(2)β(1)(HI) CD133(+VE)), transiently amplifying (α(2)β(1)(HI) CD133(-VE)) and terminally differentiated (α(2)β(1)(LOW) CD133(-VE)) cells. AR transcript and protein expression was confirmed in α(2)β(1)(HI) CD133(+VE) and CD133(-VE) progenitor cells. Flow cytometry confirmed that median (±SD) fraction of cells expressing AR were 77% (±6%) in α(2)β(1)(HI) CD133(+VE) stem cells and 68% (±12%) in α(2)β(1)(HI) CD133(-VE) transiently amplifying cells. However, 3-fold lower levels of total AR protein expression (peak and median immunofluorescence) were present in α(2)β(1)(HI) CD133(+VE) stem cells compared with differentiated cells. This finding was confirmed with dual immunostaining of prostate sections for AR and CD133, which again demonstrated low levels of AR within basal CD133(+VE) cells. Activity of the AR was confirmed in prostate progenitor cells by the expression of low levels of the AR regulated genes PSA, KLK2 and TMPRSS2. The confirmation of AR expression in prostate progenitor cells allows integration of the cancer stem cell theory with the established models of prostate cancer initiation based on a functional AR. Further study of specific AR functions in prostate stem and differentiated cells may highlight novel mechanisms of prostate homeostasis and insights into tumourigenesis
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