3,291 research outputs found

    Experience and Interpretation in Global Times: The Case of Special Education

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    This paper was delivered as a keynote address at the International Symposium for Qualitative Transformation of the Paradigm of Educational Practice and Special Education, Busan National University, South Korea, April 16, 2006. The symposium was sponsored by The Korean Research Society for Phenomenological and Hermeneutic Practice, and the Research Institute for Special Education of Busan National University

    The Specific Challenges of Globalization for Teaching and Vice Versa

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    The first part of this article examines the historical emergence of contemporary globalization phenomena through Protestantism, European colonialism, technology and the restructuring of international business enterprise, and the rise of various forms of fundamentalism. The changing mandates of teaching and education under the influence of these phenomena are identified. The second part of the article explores possibilities for teaching in the age of globalization under three themes: the recovery of personal truth, truth as shared, and truth as home.La première partie de cet article trace I'historique de I'émergence du phénomène contemporain de la mondialisation, à travers le protestantisme, le colonialisme européen, la technologie et la restructuration du monde des affaires à I'échelle internationale, Jusqu'à la montée de diverses formes de fondamentalisme. L'auteur évoque les changements de mandats dans I'enseignement et dans la formation que ces phénomènes ont provoqués. La deuxième partie de l'article présente des possibilités pour I'enseignement à I'ère de la mondialisation à partir de trois thèmes: le rétablissement de la vérité face à soi-même, de la vérité face aux autres et de la vérité face au monde

    Intracellular Responsive Lanthanide Probes

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    The use of lanthanide complexes for the detection of biologically relevant species such as anions, pH and metal ions has grown significantly over the past decade. Such probes offer significant advantages over conventional probes; sharp narrow emission lines encode detailed spectral information and allow ratiometric analysis, and their luminescence is long-lived allowing selective spectral acquisition. Many lanthanide-based probes operate in aqueous media, but few have been applied to intracellular measurements. The introductory chapter considers the design of lanthanide based probes for cellular applications. The fundamentals of lanthanide emission are discussed, and how the ligand structure needs to be carefully constructed to maximise emission efficiency. Reported bicarbonate- and pH-responsive probes, both lanthanide based and non-lanthanide based, are reviewed, leading to a set of proposed novel probe structures. The synthesis of these probes with further reasoning behind their design is described in chapter two. The chapter concludes with an overview of the complexes in terms of their emission spectral form, hydration number, HPLC and mass spectrometry properties. Chapter three presents work on bicarbonate-responsive probes. Through a series of spectral titrations, affinity constants for a range of anions were assessed. A high selectivity for bicarbonate was observed over other oxy-anions, and in the presence of protein. The complexes exhibited a mitochondrial localisation profile, and the europium luminescence intensity was modulated reversibly in response to pCO2. The terbium analogues showed negligible change under such conditions, and thus a europium to terbium emission intensity ratio could be used to calibrate pCO2. This principle was also applied to the analysis of bicarbonate levels in simulated biological fluid, and in a serum sample. Several pH-responsive complexes are described in chapter four. Key aspects of pH-probe design were highlighted in early examples, leading to the final set of probes based on reversible sulphonamide ligation. Spectral titrations were performed to assess pKa values, and the use of europium to terbium emission intensity ratios was again found to offer a convenient method for assessing pH. Unprecedented changes in CPL were found in response to pH in these systems, and gem values could be used to report upon pH. The complexes were observed to exhibit a lysosomal distribution. Finally, chapter five contains experimental procedures for each compound synthesised, as well as general experimental procedures. Both sets of complexes described in this thesis show great promise for use as well-defined intracellular probes of bicarbonate or pH

    Natural and Anthropogenic Effects on Life History Characteristics in the Side-blotched Lizard (Uta stansburiana)

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    Survival is a prerequisite for successful reproduction, and is thus intertwined with fitness. Some physiological systems can improve survival, like the immune system, but compete with other processes for resources. Because animals evolved with resource limitation, it is important to understand how these resource-allocation decisions are made. To meet this end, I performed four investigations addressing how life-history characteristics shift in side-blotched lizards (Uta stansburiana) using laboratory studies and multi-year field sampling. First, I measured metabolic rates in response to different immune challenges and different energy states in male lizards. I found that, surprisingly, cutaneous biopsies were associated with a downregulation of metabolic rate, lipopolysaccharide injection did not affect metabolic rate, and the fastest-healing individuals had the largest decrease in metabolic rate, regardless of feeding treatment. In my second experiment, female lizards were challenged with a cutaneous biopsy and follicle-stimulating hormone to force a trade-off between the reproductive and immune systems. I learned that follicle-stimulating hormone increased metabolic rates and cutaneous biopsies decreased them, and that a combination of both treatments reduced metabolic rate the most. In my third experiment, I sampled wild lizards from northern populations in eastern Oregon and southern populations in southern Utah. In the first year, longer-lived northern lizards had higher circulating corticosterone concentration, decreased reproductive investment, and increased microbiocidal ability, but the subsequent year did not hold to these trends. A subsequent common-garden experiment revealed that southern lizards were faster at healing cutaneous wounds, but lost much more body mass than the northern individuals, which healed more slowly but maintained body mass. Finally, I have conducted a 5-year field investigation addressing the life-history trade-offs associated with urbanization, which reveals interesting effects of precipitation on survival and reproductive effort at urban and rural sites

    Malaria’s Missing Number: Calculating the Human Component of R0 by a Within-Host Mechanistic Model of Plasmodium falciparum Infection and Transmission

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    Human infection by malarial parasites of the genus Plasmodium begins with the bite of an infected Anopheles mosquito. Current estimates place malaria mortality at over 650,000 individuals each year, mostly in African children. Efforts to reduce disease burden can benefit from the development of mathematical models of disease transmission. To date, however, comprehensive modeling of the parameters defining human infectivity to mosquitoes has remained elusive. Here, we describe a mechanistic within-host model of Plasmodium falciparum infection in humans and pathogen transmission to the mosquito vector. Our model incorporates the entire parasite lifecycle, including the intra-erythrocytic asexual forms responsible for disease, the onset of symptoms, the development and maturation of intra-erythrocytic gametocytes that are transmissible to Anopheles mosquitoes, and human-to-mosquito infectivity. These model components were parameterized from malaria therapy data and other studies to simulate individual infections, and the ensemble of outputs was found to reproduce the full range of patient responses to infection. Using this model, we assessed human infectivity over the course of untreated infections and examined the effects in relation to transmission intensity, expressed by the basic reproduction number R0 (defined as the number of secondary cases produced by a single typical infection in a completely susceptible population). Our studies predict that net human-to-mosquito infectivity from a single non-immune individual is on average equal to 32 fully infectious days. This estimate of mean infectivity is equivalent to calculating the human component of malarial R0. We also predict that mean daily infectivity exceeds five percent for approximately 138 days. The mechanistic framework described herein, made available as stand-alone software, will enable investigators to conduct detailed studies into theories of malaria control, including the effects of drug treatment and drug resistance on transmission

    Nature of Glycine and Its α-Carbon Radical in Aqueous Solution: A Theoretical Investigation

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    Quantum chemistry calculations and classical molecular dynamics simulations have been used to examine the equilibria in solution between the neutral and zwitterionic forms of glycine and also of the glycyl radical. The established preference (by 30 kJ mol−1) for the zwitterion of glycine was confirmed by both the quantum chemical calculations and the classical molecular dynamics simulations. The best agreement with experiment was derived from thermodynamic integration calculations of explicitly solvated systems, which gives a free energy difference of 36.6 ± 0.6 kJ mol−1. In contrast, for the glycyl radical in solution, the neutral form is preferred, with a calculated free energy difference of 54.8 ± 0.6 kJ mol−1. A detailed analysis of the microsolvation environments of each species was carried out by evaluating radial distribution functions and hydrogen bonding patterns. This analysis provides evidence that the change in preference between glycine and glycyl radical is due to the inherent gas-phase stability of the neutral α-carbon radical rather than to any significant difference in the solvation behavior of the constituent species

    Vaccinia Virus Gene B7R Encodes an 18-kDa Protein That is Resident in the Endoplasmic Reticulum and Affects Virus Virulence

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    AbstractThis paper presents a characterisation of vaccinia virus (VV) gene B7R that was predicted to encode a polypeptide of 182 amino acids with an N-terminal signal peptide. In vitro transcription and translation analysis showed the B7R gene product was a 21-kDa protein that, in the presence of microsomes, was processed into an 18-kDa mature form. The 18-kDa form associated with the microsomal membranes and was within the lumen of the vesicle where it was inaccessible to exogenous protease or an antibody raised against the B7R C terminus. Within VV-infected cells, the 18-kDa form of B7R was detected late during infection in the endoplasmic reticulum where it colocalised with protein disulphide isomerase. The B7R protein was detected neither in the culture supernatant nor associated with virus particles. A virus deletion mutant lacking the B7R gene and a revertant virus were constructed. Compared to wild-type and revertant viruses, the deletion mutant replicated normally in cell culture and had unaltered virulence in a murine intranasal model of infection. However, the deletion mutant was attenuated in a murine intradermal model where it induced a smaller lesion than the control viruses

    Modeling Within-Host Effects of Drugs on Plasmodium falciparum Transmission and Prospects for Malaria Elimination

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    Achieving a theoretical foundation for malaria elimination will require a detailed understanding of the quantitative relationships between patient treatment-seeking behavior, treatment coverage, and the effects of curative therapies that also block Plasmodium parasite transmission to mosquito vectors. Here, we report a mechanistic, within-host mathematical model that uses pharmacokinetic (PK) and pharmacodynamic (PD) data to simulate the effects of artemisinin-based combination therapies (ACTs) on Plasmodium falciparum transmission. To contextualize this model, we created a set of global maps of the fold reductions that would be necessary to reduce the malaria RC (i.e. its basic reproductive number under control) to below 1 and thus interrupt transmission. This modeling was applied to low-transmission settings, defined as having a R0<10 based on 2010 data. Our modeling predicts that treating 93–98% of symptomatic infections with an ACT within five days of fever onset would interrupt malaria transmission for ∼91% of the at-risk population of Southeast Asia and ∼74% of the global at-risk population, and lead these populations towards malaria elimination. This level of treatment coverage corresponds to an estimated 81–85% of all infected individuals in these settings. At this coverage level with ACTs, the addition of the gametocytocidal agent primaquine affords no major gains in transmission reduction. Indeed, we estimate that it would require switching ∼180 people from ACTs to ACTs plus primaquine to achieve the same transmission reduction as switching a single individual from untreated to treated with ACTs. Our model thus predicts that the addition of gametocytocidal drugs to treatment regimens provides very small population-wide benefits and that the focus of control efforts in Southeast Asia should be on increasing prompt ACT coverage. Prospects for elimination in much of Sub-Saharan Africa appear far less favorable currently, due to high rates of infection and less frequent and less rapid treatment

    Stoichiometric and Stable Isotope Ratios of Wild Lizards in an Urban Landscape Vary with Reproduction, Physiology, Space and Time

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    Spatial and temporal variation in stoichiometric and stable isotope ratios of animals contains ecological information that we are just beginning to understand. In both field and lab studies, stoichiometric or isotopic ratios are related to physiological mechanisms underlying nutrition or stress. Conservation and ecosystem ecology may be informed by isotopic data that can be rapidly and non-lethally collected from wild animals, especially where human activity leaves an isotopic signature (e.g. via introduction of chemical fertilizers, ornamental or other non-native plants or organic detritus). We examined spatial and temporal variation in stoichiometric and stable isotope ratios of the toes of Uta stansburiana (side-blotched lizards) living in urban and rural areas in and around St. George, Utah. We found substantial spatial and temporal variation as well as context-dependent co-variation with reproductive physiological parameters, although certain key predictions such as the relationship between δ15N and body condition were not supported. We suggest that landscape change through urbanization can have profound effects on wild animal physiology and that stoichiometric and stable isotope ratios can provide unique insights into the mechanisms underlying these processes

    Frost-Free Record Reconstruction for Eastern Massachusetts, 1733-1980

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    A reconstruction methodology utilizing such varied documents as diaries, agricultural journals, U.S. Weather Bureau killing frost records and instrumental records is discussed. A resultant 248-year frost record for eastern Massachusetts exhibits marked variations in the length of the growing season, that occur on a time scale of approximately 70 years. There is an apparent systematic long-term relationship between the timing of spring and fall killing frosts and the last 100 years of record reveals a decline in year-to-year variability
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