248 research outputs found

    The Education Combination Toolkit

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    Drawing on both research and the lived experiences of students, parents, and educators from across the country, this paper describes how the right combination of resources can make a difference for students' learning experiences.The Education Combination provides state and district leaders, educators, families, and communityadvocates with an overview of each dimension, including:A vision for what it should look likeResearch-backed reasons for why it mattersKey questions to considerExamples of challenges and trends from states, districts, and school

    The Occurrence of Photorhabdus-Like Toxin Complexes in Bacillus thuringiensis

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    Recently, genomic sequencing of a Bacillus thuringiensis (Bt) isolate from our collection revealed the presence of an apparent operon encoding an insecticidal toxin complex (Tca) similar to that first described from the entomopathogen Photorhabdus luminescens. To determine whether these genes are widespread among Bt strains, we screened isolates from the collection for the presence of tccC, one of the genes needed for the expression of fully functional toxin complexes. Among 81 isolates chosen to represent commonly encountered biochemical phenotypes, 17 were found to possess a tccC. Phylogenetic analysis of the 81 isolates by multilocus sequence typing revealed that all the isolates possessing a tccC gene were restricted to two sequence types related to Bt varieties morrisoni, tenebrionis, israelensis and toumanoffi. Sequencing of the ∼17 kb tca operon from two isolates representing each of the two sequence types revealed >99% sequence identity. Optical mapping of DNA from Bt isolates representing each of the sequence types revealed nearly identical plasmids of ca. 333 and 338 kbp, respectively. Selected isolates were found to be toxic to gypsy moth larvae, but were not as effective as a commercial strain of Bt kurstaki. Some isolates were found to inhibit growth of Colorado potato beetle. Custom Taqman® relative quantitative real-time PCR assays for Tc-encoding Bt revealed both tcaA and tcaB genes were expressed within infected gypsy moth larvae

    Power grid complex network evolutions for the smart grid

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    The shift towards an energy grid dominated by prosumers (consumers and producers of energy) will inevitably have repercussions on the electricity distribution infrastructure. Today the grid is a hierarchical one delivering energy from large scale facilities to end-users. Tomorrow it will be a capillary infrastructure at the medium and low voltage levels that will support local energy trading among prosumers. We investigate how different network topologies and growth models facilitate a more efficient and reliable network, and how they can facilitate the emergence of a decentralized electricity market. We show how connectivity plays an important role in improving the properties of reliability and path-cost reduction. Our results indicate that a specific type of evolution balances best the ratio between increased connectivity and costs to achieve the network growth.

    Development of quality indicators for monitoring outcomes of frail elderly hospitalised in acute care health settings: Study Protocol

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    Background: Frail older people admitted to acute care hospitals are at risk of a range of adverse outcomes, including geriatric syndromes, although targeted care strategies can improve health outcomes for these patients. It is therefore important to assess inter-hospital variation in performance in order to plan and resource improvement programs. Clinical quality outcome indicators provide a mechanism for identifying variation in performance over time and between hospitals, however to date there has been no routine use of such indicators in acute care settings. A barrier to using quality indicators is lack of access to routinely collected clinical data. The interRAI Acute Care (AC) assessment system supports comprehensive geriatric assessment of older people within routine daily practice in hospital and includes process and outcome data pertaining to geriatric syndromes. This paper reports the study protocol for the development of aged care quality indicators for acute care hospitals. Methods/Design. The study will be conducted in three phases:. 1. Development of a preliminary inclusive set of quality indicators set based on a literature review and expert panel consultation,. 2. A prospective field study including recruitment of 480 patients aged 70 years or older across 9 Australian hospitals. Each patient will be assessed on admission and discharge using the interRAI AC, and will undergo daily monitoring to observe outcomes. Medical records will be independently audited, and. 3. Analysis and compilation of a definitive quality indicator set, including two anonymous voting rounds for quality indicator inclusion by the expert panel. Discussion. The approach to quality indicators proposed in this protocol has four distinct advantages over previous efforts: the quality indicators focus on outcomes; they can be collected as part of a routinely applied clinical information and decision support system; the clinical data will be robust and will contribute to better understanding variations in hospital care of older patients; The quality indicators will have international relevance as they will be built on the interRAI assessment instrument, an internationally recognised clinical system

    Incidence and prevalence of dementia in linked administrative health data in Saskatchewan, Canada: a retrospective cohort study.

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    Determining the epidemiology of dementia among the population as a whole in specific jurisdictions - including the long-term care population-is essential to providing appropriate care. The objectives of this study were to use linked administrative databases in the province of Saskatchewan to determine the 12-month incidence and prevalence of dementia for the 2012/13 period (1) among individuals aged 45 and older in the province of Saskatchewan, (2) according to age group and sex, and (3) according to diagnosis code and other case definition criteria

    A Role for the Unfolded Protein Response (UPR) in Virulence and Antifungal Susceptibility in Aspergillus fumigatus

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    Filamentous fungi rely heavily on the secretory pathway, both for the delivery of cell wall components to the hyphal tip and the production and secretion of extracellular hydrolytic enzymes needed to support growth on polymeric substrates. Increased demand on the secretory system exerts stress on the endoplasmic reticulum (ER), which is countered by the activation of a coordinated stress response pathway termed the unfolded protein response (UPR). To determine the contribution of the UPR to the growth and virulence of the filamentous fungal pathogen Aspergillus fumigatus, we disrupted the hacA gene, encoding the major transcriptional regulator of the UPR. The ΔhacA mutant was unable to activate the UPR in response to ER stress and was hypersensitive to agents that disrupt ER homeostasis or the cell wall. Failure to induce the UPR did not affect radial growth on rich medium at 37°C, but cell wall integrity was disrupted at 45°C, resulting in a dramatic loss in viability. The ΔhacA mutant displayed a reduced capacity for protease secretion and was growth-impaired when challenged to assimilate nutrients from complex substrates. In addition, the ΔhacA mutant exhibited increased susceptibility to current antifungal agents that disrupt the membrane or cell wall and had attenuated virulence in multiple mouse models of invasive aspergillosis. These results demonstrate the importance of ER homeostasis to the growth and virulence of A. fumigatus and suggest that targeting the UPR, either alone or in combination with other antifungal drugs, would be an effective antifungal strategy

    Deiminated proteins and extracellular vesicles - novel serum biomarkers in whales and Orca

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    Peptidylarginine deiminases (PADs) are a family of phylogenetically conserved calcium-dependent enzymes which cause post-translational protein deimination. This can result in neoepitope generation, affect gene regulation and allow for protein moonlighting via functional and structural changes in target proteins. Extracellular vesicles (EVs) carry cargo proteins and genetic material and are released from cells as part of cellular communication. EVs are found in most body fluids where they can be useful biomarkers for assessment of health status. Here, serum-derived EVs were profiled, and post-translationally deiminated proteins and EV-related microRNAs are described in 5 ceataceans: minke whale, fin whale, humpback whale, Cuvier's beaked whale and orca. EV-serum profiles were assessed by transmission electron microscopy and nanoparticle tracking analysis. EV profiles varied between the 5 species and were identified to contain deiminated proteins and selected key inflammatory and metabolic microRNAs. A range of proteins, critical for immune responses and metabolism were identified to be deiminated in cetacean sera, with some shared KEGG pathways of deiminated proteins relating to immunity and physiology, while some KEGG pathways were species-specific. This is the first study to characterise and profile EVs and to report deiminated proteins and putative effects of protein-protein interaction networks via such post-translationald deimination in cetaceans, revealing key immune and metabolic factors to undergo this post-translational modification. Deiminated proteins and EVs profiles may possibly be developed as new biomarkers for assessing health status of sea mammals

    Gene and genon concept: coding versus regulation: A conceptual and information-theoretic analysis of genetic storage and expression in the light of modern molecular biology

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    We analyse here the definition of the gene in order to distinguish, on the basis of modern insight in molecular biology, what the gene is coding for, namely a specific polypeptide, and how its expression is realized and controlled. Before the coding role of the DNA was discovered, a gene was identified with a specific phenotypic trait, from Mendel through Morgan up to Benzer. Subsequently, however, molecular biologists ventured to define a gene at the level of the DNA sequence in terms of coding. As is becoming ever more evident, the relations between information stored at DNA level and functional products are very intricate, and the regulatory aspects are as important and essential as the information coding for products. This approach led, thus, to a conceptual hybrid that confused coding, regulation and functional aspects. In this essay, we develop a definition of the gene that once again starts from the functional aspect. A cellular function can be represented by a polypeptide or an RNA. In the case of the polypeptide, its biochemical identity is determined by the mRNA prior to translation, and that is where we locate the gene. The steps from specific, but possibly separated sequence fragments at DNA level to that final mRNA then can be analysed in terms of regulation. For that purpose, we coin the new term “genon”. In that manner, we can clearly separate product and regulative information while keeping the fundamental relation between coding and function without the need to introduce a conceptual hybrid. In mRNA, the program regulating the expression of a gene is superimposed onto and added to the coding sequence in cis - we call it the genon. The complementary external control of a given mRNA by trans-acting factors is incorporated in its transgenon. A consequence of this definition is that, in eukaryotes, the gene is, in most cases, not yet present at DNA level. Rather, it is assembled by RNA processing, including differential splicing, from various pieces, as steered by the genon. It emerges finally as an uninterrupted nucleic acid sequence at mRNA level just prior to translation, in faithful correspondence with the amino acid sequence to be produced as a polypeptide. After translation, the genon has fulfilled its role and expires. The distinction between the protein coding information as materialised in the final polypeptide and the processing information represented by the genon allows us to set up a new information theoretic scheme. The standard sequence information determined by the genetic code expresses the relation between coding sequence and product. Backward analysis asks from which coding region in the DNA a given polypeptide originates. The (more interesting) forward analysis asks in how many polypeptides of how many different types a given DNA segment is expressed. This concerns the control of the expression process for which we have introduced the genon concept. Thus, the information theoretic analysis can capture the complementary aspects of coding and regulation, of gene and genon
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