112 research outputs found

    Siting Transmission Lines in a Changed Milieu: Evolving Notions of the "Public Interest" In Balancing State and Regional Considerations

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    This Article discusses how state public utility law presents a barrier to the siting of new high voltage transmission lines to serve renewable resources, and how states could approach its evolution in order to preserve a role for state regulators in a new energy economy in which renewable energy will play a significant role. The traditional approach to determining the "public interest" in siting transmission lines is well on its way to obsolescence. Two developments over the past fifteen years have begun to challenge this paradigm. First, policies at the federal level and in many states have encouraged increased competition in generation, contributing to de-monopolization of the bulk power side of the industry. Second, the increased emphasis on environmental, energy independence, and other public policy objectives, has resulted in a dramatically increased demand for renewable energy, particularly given heightened attention to climate change. Given that wind power -- the most economically viable renewable resource on a bulk power basis -- is feasible predominantly in locations far removed from, load centers, the demand for new multistate transmission facilities has been brought clearly into focus. After an introduction in Part I, Part II describes the existing arrangements in several resource rich Western states for siting new transmission lines, and the coexistence of those arrangements with a conventional understanding of the public interest in determining need and addressing environmental concerns under traditional state transmission siting laws. Part III discusses transmission issues related to the competitive wholesale market and increased attention to climate change and highlights how federal law has expanded to accommodate some of these concerns. Part IV emphasizes the need for a new definition of the public interest which might better reflect these new market circumstances and opportunities, and highlights the two main barriers to this: 1) legislative and/or regulatory inertia and 2) an outdated cost-allocation model. The public interest under most state siting statutes is sufficiently capacious to give regulators some flexibility to evolve, but in other instances legislative action may be needed. In addition, the state cost-of-service ratemaking model must evolve to a more regional approach to allocating the costs of new transmission

    Quantitative Analysis of Histone Modifications: Formaldehyde Is a Source of Pathological N6-Formyllysine That Is Refractory to Histone Deacetylases

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    Aberrant protein modifications play an important role in the pathophysiology of many human diseases, in terms of both dysfunction of physiological modifications and the formation of pathological modifications by reaction of proteins with endogenous electrophiles. Recent studies have identified a chemical homolog of lysine acetylation, N[superscript 6]-formyllysine, as an abundant modification of histone and chromatin proteins, one possible source of which is the reaction of lysine with 3′-formylphosphate residues from DNA oxidation. Using a new liquid chromatography-coupled to tandem mass spectrometry method to quantify all N[superscript 6]-methyl-, -acetyl- and -formyl-lysine modifications, we now report that endogenous formaldehyde is a major source of N[superscript 6]-formyllysine and that this adduct is widespread among cellular proteins in all compartments. N[superscript 6]-formyllysine was evenly distributed among different classes of histone proteins from human TK6 cells at 1–4 modifications per 10[superscript 4] lysines, which contrasted strongly with lysine acetylation and mono-, di-, and tri-methylation levels of 1.5-380, 5-870, 0-1400, and 0-390 per 10[superscript 4] lysines, respectively. While isotope labeling studies revealed that lysine demethylation is not a source of N[superscript 6]-formyllysine in histones, formaldehyde exposure was observed to cause a dose-dependent increase in N[superscript 6]-formyllysine, with use of [[superscript 13]C,[superscript 2]H[subscript 2]]-formaldehyde revealing unchanged levels of adducts derived from endogenous sources. Inhibitors of class I and class II histone deacetylases did not affect the levels of N[superscript 6]-formyllysine in TK6 cells, and the class III histone deacetylase, SIRT1, had minimal activity (<10%) with a peptide substrate containing the formyl adduct. These data suggest that N[superscript 6]-formyllysine is refractory to removal by histone deacetylases, which supports the idea that this abundant protein modification could interfere with normal regulation of gene expression if it arises at conserved sites of physiological protein secondary modification

    Commentary: mechanistic considerations for associations between formaldehyde exposure and nasopharyngeal carcinoma

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    Occupational exposure to formaldehyde has been linked to nasopharyngeal carcinoma. To date, mechanistic explanations for this association have primarily focused on formaldehyde-induced cytotoxicity, regenerative hyperplasia and DNA damage. However, recent studies broaden the potential mechanisms as it is now well established that formaldehyde dehydrogenase, identical to S-nitrosoglutathione reductase, is an important mediator of cGMP-independent nitric oxide signaling pathways. We have previously described mechanisms by which formaldehyde can influence nitrosothiol homeostasis thereby leading to changes in pulmonary physiology. Considering evidences that nitrosothiols govern the Epstein-Barr virus infection cycle, and that the virus is strongly implicated in the etiology of nasopharyngeal carcinoma, studies are needed to examine the potential for formaldehyde to reactivate the Epstein-Barr virus as well as additively or synergistically interact with the virus to potentiate epithelial cell transformation

    Cancer effects of formaldehyde: a proposal for an indoor air guideline value

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    Formaldehyde is a ubiquitous indoor air pollutant that is classified as “Carcinogenic to humans (Group 1)” (IARC, Formaldehyde, 2-butoxyethanol and 1-tert-butoxypropanol-2-ol. IARC monographs on the evaluation of carcinogenic risks to humans, vol 88. World Health Organization, Lyon, pp 39–325, 2006). For nasal cancer in rats, the exposure–response relationship is highly non-linear, supporting a no-observed-adverse-effect level (NOAEL) that allows setting a guideline value. Epidemiological studies reported no increased incidence of nasopharyngeal cancer in humans below a mean level of 1 ppm and peak levels below 4 ppm, consistent with results from rat studies. Rat studies indicate that cytotoxicity-induced cell proliferation (NOAEL at 1 ppm) is a key mechanism in development of nasal cancer. However, the linear unit risk approach that is based on conservative (“worst-case”) considerations is also used for risk characterization of formaldehyde exposures. Lymphohematopoietic malignancies are not observed consistently in animal studies and if caused by formaldehyde in humans, they are high-dose phenomenons with non-linear exposure–response relationships. Apparently, these diseases are not reported in epidemiological studies at peak exposures below 2 ppm and average exposures below 0.5 ppm. At the similar airborne exposure levels in rodents, the nasal cancer effect is much more prominent than lymphohematopoietic malignancies. Thus, prevention of nasal cancer is considered to prevent lymphohematopoietic malignancies. Departing from the rat studies, the guideline value of the WHO (Air quality guidelines for Europe, 2nd edn. World Health Organization, Regional Office for Europe, Copenhagen, pp 87–91, 2000), 0.08 ppm (0.1 mg m−3) formaldehyde, is considered preventive of carcinogenic effects in compliance with epidemiological findings
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