178 research outputs found

    From Barriers to Opportunities: Renewable Energy Issues in Law and Policy

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    A Report on the Work of the Renewable Energy and International Law (REIL) Project, 2006-200

    A tetraethylene glycol coat gives gold nanoparticles long in vivo half-lives with minimal increase in size

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    In this study, we describe the experiments determining whether coating gold nanoparticles with tetraethylene glycol (TEG) provides pharmacologically relevant advantages, such as increased serum half-life and resistance to protein adsorption. Monodisperse TEG-coated, NaBH4-reduced gold nanoparticles with a hydrodynamic size comparable to albumin were synthesized by reducing gold chloride with NaBH4 under alkaline conditions in the presence of TEG-SH. The particles were characterized by gel electrophoresis, column chromatography, and transmission electron microscopy. The nanoparticles were subsequently injected intravenously into mice, and their half-lives and final destinations were determined via photometric analysis, light microscopy (LM), and transmission electron microscopy. The TEG particles had a long half-life (~400 minutes) that was not influenced by splenectomy. After 500 minutes of injection, TEG particles were found in kidney proximal tubule cell vesicles and in spleen red and white pulp. The particles induced apoptosis in the spleen red pulp but not in white pulp or the kidney. Some of the TEG particles appeared to have undergone ligand exchange reactions that increased their charge. The TEG particles were shown to be resistant to nonspecific protein adsorption, as judged by gel electrophoresis and column chromatography. These results demonstrate that naturally monodisperse, small-sized gold nanoparticles coated with TEG have long in vivo plasma half-lives, are minimally toxic, and are resistant to protein adsorption. This suggests that a TEG coating should be considered as an alternative to a polyethylene glycol coating, which is polydisperse and of much larger size

    From Debate to Design: Issues in Clean Energy and Climate Change Law and Policy

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    A report on the work of the REIL Network 2007-200

    Associative Cortex Features in the First Olfactory Brain Relay Station

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    SummarySynchronized firing of mitral cells (MCs) in the olfactory bulb (OB) has been hypothesized to help bind information together in olfactory cortex (OC). In this survey of synchronized firing by suspected MCs in awake, behaving vertebrates, we find the surprising result that synchronized firing conveys information on odor value (“Is it rewarded?”) rather than odor identity (“What is the odor?”). We observed that as mice learned to discriminate between odors, synchronous firing responses to the rewarded and unrewarded odors became divergent. Furthermore, adrenergic blockage decreases the magnitude of odor divergence of synchronous trains, suggesting that MCs contribute to decision-making through adrenergic-modulated synchronized firing. Thus, in the olfactory system information on stimulus reward is found in MCs one synapse away from the sensory neuron

    A tetraethylene glycol coat gives gold nanoparticles long in vivo half-lives with minimal increase in size

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    In this study, we describe the experiments determining whether coating gold nanoparticles with tetraethylene glycol (TEG) provides pharmacologically relevant advantages, such as increased serum half-life and resistance to protein adsorption. Monodisperse TEG-coated, NaBH(4)-reduced gold nanoparticles with a hydrodynamic size comparable to albumin were synthesized by reducing gold chloride with NaBH(4) under alkaline conditions in the presence of TEG-SH. The particles were characterized by gel electrophoresis, column chromatography, and transmission electron microscopy. The nanoparticles were subsequently injected intravenously into mice, and their half-lives and final destinations were determined via photometric analysis, light microscopy (LM), and transmission electron microscopy. The TEG particles had a long half-life (~400 minutes) that was not influenced by splenectomy. After 500 minutes of injection, TEG particles were found in kidney proximal tubule cell vesicles and in spleen red and white pulp. The particles induced apoptosis in the spleen red pulp but not in white pulp or the kidney. Some of the TEG particles appeared to have undergone ligand exchange reactions that increased their charge. The TEG particles were shown to be resistant to nonspecific protein adsorption, as judged by gel electrophoresis and column chromatography. These results demonstrate that naturally monodisperse, small-sized gold nanoparticles coated with TEG have long in vivo plasma half-lives, are minimally toxic, and are resistant to protein adsorption. This suggests that a TEG coating should be considered as an alternative to a polyethylene glycol coating, which is polydisperse and of much larger size

    Apolipoprotein E4 in Macrophages Enhances Atherogenesis in a Low Density Lipoprotein Receptor-dependent Manner

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    Apolipoprotein E (apoE) and the low density lipoprotein receptor (LDLr) are well recognized determinants of atherosclerosis. In addition to hepatocytes, where both are highly expressed and contribute to plasma lipoprotein clearance, they are expressed in vascular cells and macrophages. In this study, we examined the effects of human apoE isoforms and LDLr levels in atherogenic pathways in primary macrophages ex vivo and atherosclerosis development after bone marrow transfer in vivo using mice expressing human apoE isoforms and different levels of LDLr expression. Increases in LDLr expression significantly increased cholesterol delivery into macrophages in culture, and the effects were more prominent with lipoproteins containing apoE4 than those containing apoE3. Conversely, increased LDLr expression reduced cholesterol efflux in macrophages expressing apoE4 but not in macrophages expressing apoE3. Furthermore, apoE3 protected VLDL from oxidation in vitro more than did apoE4. In LDLr-deficient mice expressing the human apoE4 isoform, Apoe4/4 Ldlr−/−, the replacement of bone marrow cells with those expressing LDLr increased atherosclerotic lesions in a dose-dependent manner compared with mice transplanted with cells having no LDLr. In contrast, atherosclerosis in Apoe3/3 Ldlr−/− mice, expressing the human apoE3 isoform, did not differ by the levels of macrophage LDLr expression. Our results demonstrate that apoE4, but not apoE3, in macrophages enhances atherosclerotic plaque development in mice in an LDLr-dependent manner and suggests that this interaction may contribute to the association of apoE4 with an increased cardiovascular risk in humans

    Zika virus tropism and interactions in myelinating neural cell cultures: CNS cells and myelin are preferentially affected

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    The recent global outbreak of Zika virus (ZIKV) infection has been linked to severe neurological disorders affecting the peripheral and central nervous systems (PNS and CNS, respectively). The pathobiology underlying these diverse clinical phenotypes are the subject of intense research; however, even the principal neural cell types vulnerable to productive Zika infection remain poorly characterised. Here we used CNS and PNS myelinating cultures from wild type and Ifnar1 knockout mice to examine neuronal and glial tropism and short-term consequences of direct infection with a Brazilian variant of ZIKV. Cell cultures were infected pre- or post-myelination for various intervals, then stained with cell-type and ZIKV-specific antibodies. In bypassing systemic immunity using ex vivo culture, and the type I interferon response in Ifnar1 deficient cells, we were able to evaluate the intrinsic infectivity of neural cells. Through systematic quantification of ZIKV infected cells in myelinating cultures, we found that ZIKV infection is enhanced in the absence of the type I interferon responses and that CNS cells are considerably more susceptible to infection than PNS cells. In particular, we demonstrate that CNS axons and myelinating oligodendrocytes are especially vulnerable to injury. These results have implications for understanding the pathobiology of neurological symptoms associated with ZIKV infection. Furthermore, we provide a quantifiable ex vivo infection model that can be used for fundamental and therapeutic studies on viral neuroinvasion and its consequences

    School Counseling Site Supervision: Training Recommendations to Benefit School Counselor Interns and Site Supervisors

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    The importance of supervision is supported in the research literature. Site supervision in school counseling does not require formal training. The absence of formal training has potential implications for the novice school counselor, the P-12 students they serve, and future school counseling supervisees. The authors compare current training models and explore best practices to improve site supervision for school counseling interns. accreditation, ethics, and current needs in school counseling for the school counselor intern and the site supervisor. Finally, the authors review supervision training and models, accreditation, ethics, and current needs for the school counselor intern and the site supervisor, including a recommendation for a school supervisory endorsement
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