279 research outputs found

    His Father\u27s World

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    The Child

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    Sequences of Learning Types for Organizational Ambidexterity

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    Ambidexterity involves strategies for effectively managing the inherent tensions between short-term stability and long-term investments, a challenge known as the exploitation-exploration paradox. Despite the acknowledged importance of learning in the context of ambidexterity, there is a limited understanding of how various forms of organizational learning are employed over time in projects focused on either exploitation or exploration. This gap in knowledge is significant because the timing and sources of knowledge acquisition that support innovation can significantly impact the success of an ambidextrous approach. In essence, ambidexterity not only requires balancing the conflicting demands of exploitation and exploration but also necessitates the integration of both internal and external knowledge sources.https://dc.suffolk.edu/ciclseries/1002/thumbnail.jp

    Habitat characterization of Saskatchewan's Dakota skipper, Hesperia dacotae population

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    The Dakota skipper, Hesperia dacotae (Skinner, 1911) (Hesperiidae), is an at-risk butterfly species that inhabits the mesic mixed-grass prairie. The Dakota skipper is listed endangered under the federal Species at Risk Act. Loss of native prairie is the main factor driving declines in Dakota skipper habitat and species abundance is assumed to be declining. Currently, there is a knowledge gap pertaining to habitat associations and availability of Saskatchewan populations. This information is critical to construct a recovery plan to secure Dakota skipper populations. The first objective was to better understand the environmental associations of Dakota skipper habitat through landscape, vegetation, soil, climate, microclimate, and Hesperiidae butterfly species occupancy. Data collection was conducted in 2015 and 2016; of the 46 sites surveyed; nine were Dakota skipper positive (i.e., present) sites and 37 were negative (i.e., non-detect) sites. Results indicated that plant community composition was not a significant predictor of Dakota skipper presence, but three plant species were significantly associated with the species; Pediomelum argophyllum (Pursh) J.W.Grimes (Fabaceae), Zizia aptera (A.Gray) Fernald (Apiaceae), and Schizachyrium scoparium (Michx.) Nash (Poaceae). No soil or climate variables were significant predictors of Dakota skipper presence; however the species was significantly associated with steep slopes. Warmer maximum and average ground-level temperatures were also associated with Dakota skipper presence. The second objective was to determine Dakota skipper habitat suitability and distribution through a landscape-level habitat distribution model based on climate normal, soil, and landscape variables. Data were obtained from publically available Dakota skipper observation locations and in situ data collection within Saskatchewan. A total of 66 unique survey sites were obtained; 28 of these sites were Dakota skipper positive sites whereas the remaining 38 were negative sites. A habitat distribution map ranks the suitability of Dakota skipper habitat throughout southeastern Saskatchewan. Results indicated that although the Dakota skipper inhabits the mesic mixed-grass prairie region, only 11% of this region contains exceptional habitat (habitat probabilities 0.71-1) for this species. These areas contain a significantly lower mean diurnal temperature range and a higher ammonium soil content. I conclude that although the Dakota skipper inhabits the native mesic mixed-grass prairie region, environmental constraints including climate, soil, and landscape variables restrict this species to a more limited area of available habitat then initially thought. A landscape-level habitat suitability and distribution map complemented by habitat associations allows for more accurately targeted surveys, informs managers developing conservation and management plans, and allows for an overall better understanding of the Dakota skipper’s current situation in southeastern Saskatchewan. Findings indicate that additional Dakota skipper populations are likely in Saskatchewan and future targeted surveys will allow for a full evaluation of this species’ distribution and conservation status

    A Modular One-Generation Reproduction Study as a Flexible Testing System for Regulatory Safety Assessment

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    The European Union’s Registration, Evaluation and Authorisation of Chemicals (REACH) legislation mandates testing and evaluation of approximately 30,000 existing substances within a short period of time, beginning with the most widely used “high production volume” (HPV) chemicals. REACH testing requirements for the roughly 3000 HPV chemicals specify three separate tests for reproductive toxicity: two developmental toxicity studies on different animal species (OECD Test Guideline 414) and a two-generation reproduction toxicity study (OECD TG 416). These studies are highly costly in both economic and animal welfare terms. OECD TG 416 is a fertility study intended to evaluate reproductive performance of animals in the P and F1-generations following repeated exposure to a test substance. It can also be used to detect adverse effects on structural and functional development. Thus, it has conventionally been preferred to the one-generation study (OECD TG 415). Recently, the Agricultural Chemical Safety Assessment (ACSA) Technical Committee of the ILSI Health and Environmental Sciences Institute (HESI) proposed that routine two-generation studies could in most cases be replaced with an “enhanced” one-generation study (Reuter et al. [1]). The flexible design proposed by HESI-ACSA allows for the addition of one or more specialised modules, if triggered (e.g. production of a second generation or the investigation of classical developmental toxicity or developmental neuro- or immunotoxicity). Significantly, however, the HESI-ACSA proposal was designed for use in the safety assessment of pesticidal, as opposed to industrial, chemicals. Thus for the purposes of REACH, a streamlined one-generation study that also examines structural development would be the most efficient means of addressing current information requirements for HPV chemicals. This study represents a flexible testing system that can be modified to meet regulatory needs in a variety of sectors

    Levels of Citation of Nonhuman Animal Studies Conducted at a Canadian Research Hospital

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    The publication of scientific articles that receive few or no citations raises questions of the appropriate use of resources as well as ethics. In the case of animal research, the ethics issue extends beyond human patients to nonhuman animals, as the research subjects them to pain and, typically, to death. This study is a citation analysis of animal research conducted at Toronto\u27s Hospital for Sick Children (HSC). Of the 594 publications (1990 to 1995) on animal research by affiliates of HSC, 29% received Iower than 10 citations in a 10-year period. We compare the research history of 13 best and 13 worst HSC scientists. Worst researchers continue to do infrequently cited research. Recommendations indicate how institutions and researchers can become more effective and accountable

    Act on the Registration and Evaluation of Chemicals (K-REACH) and replacement, reduction or refinement best practices

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    Objectives - Korea’s Act on the Registration and Evaluation of Chemicals (K-REACH) was enacted for the protection of human health and the environment in 2015. Considering that about 2000 new substances are introduced annually across the globe, the extent of animal testing requirement could be overwhelming unless regulators and companies work proactively to institute and enforce global best practices to replace, reduce or refine animal use. In this review, the way to reduce the animal use for K-REACH is discussed. Methods - Background of the enforcement of the K-REACH and its details was reviewed along with the papers and regulatory documents regarding the limitation of animal experiments and its alternatives in order to discuss the regulatory adoption of alternative tests. Results - Depending on the tonnage of the chemical used, the data required ranges from acute and other short-term studies for a single exposure route to testing via multiple exposure routes and costly, longer-term studies such as a full two-generation reproducibility toxicity. The European Registration, Evaluation, Authorization and Restriction of Chemicals regulation provides for mandatory sharing of vertebrate test data to avoid unnecessary duplication of animal use and test costs, and obligation to revise data requirements and test guidelines “as soon as possible” after relevant, validated replacement, reduction or refinement (3R) methods become available. Furthermore, the Organization for Economic Cooperation and Development actively accepts alternative animal tests and 3R to chemical toxicity tests. Conclusions - Alternative tests which are more ethical and efficient than animal experiments should be widely used to assess the toxicity of chemicals for K-REACH registration. The relevant regulatory agencies will have to make efforts to actively adopt and uptake new alternative tests and 3R to K-REACH

    The Development of New Concepts for Assessing Reproductive Toxicity Applicable to Large Scale Toxicological Programmes

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    Large scale toxicological testing programmes which are currently ongoing such as the new European chemical legislation REACH require the development of new integrated testing strategies rather than applying traditional testing schemes to thousands of chemicals. The current practice of requiring in vivo testing for every possible adverse effect endanger the success of these programmes due (i) to limited testing facilities and sufficient capacity of scientific/technical knowledge for reproductive toxicity; (ii) an unacceptable number of laboratory animals involved (iii) an intolerable number of chemicals classified as false positive. A key aspect of the implementation of new testing strategies is the determination of prevalence of reproductive toxicity in the universe of industrial chemicals. Prevalences are relevant in order to be aware on the expected rate of false classification during the toxicological testing and to implement appropriate measures for their avoidance. Furthermore, a detailed understanding on the subendpoints affected by reproductive toxicants and the underlying mechanisms will lead to more science based testing strategies integrating alternative methods without compromising the protection of consumers

    Francisella tularensis 2-C-Methyl-D-Erythritol 4-Phosphate Cytidylyltransferase: Kinetic Characterization and Phosphoregulation

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    Deliberate and natural outbreaks of infectious disease, the prevalence of antibiotic resistant strains, and the ease by which antibiotic resistant bacteria can be intentionally engineered all underscore the necessity of effective vaccines and continued development of novel antimicrobial/antiviral therapeutics. Isoprenes, a group of molecules fundamentally involved in a variety of crucial biological functions, are derived from either the mevalonic acid (MVA) or methylerythritol phosphate (MEP) pathway. While mammals utilize the MVA pathway, many bacteria utilize the MEP pathway, highlighting the latter as an attractive target for antibiotic development. In this report we describe the cloning and characterization of Francisella tularensis MEP cytidylyltransferase, a MEP pathway enzyme and potential target for antibiotic development. Size exclusion chromatography indicates the protein exists as a dimer in solution. Enzyme assays produced an apparent , , , , and a . The enzyme exhibits a strict preference for Mg+2 as a divalent cation and CTP as the nucleotide. Titanium dioxide chromatography-tandem mass spectrometry identified Thr141 as a site of phosphorylation. T141D and T141E site-directed mutants are catalytically inactive, suggesting a mechanism for post-translational control of metabolic flux through the F. tularensis MEP pathway. Overall, our study suggests that MEP cytidylyltransferase is an excellent target for the development of novel antibiotics against F. tularensis
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