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Investment opportunities in electric power generation have changed dramatically since electricity industry restructuring first began. In contrast to regulated utilities adding capacity in line with central planning and regulation, power plant investment is now more often made by independent companies who market power across multiple utility jurisdictions. Because the regulatory approval process is long and outcomes uncertain, developers often plan multiple options for a given development budget. As more information is revealed about the future prospects at different sites, options are abandoned sequentially until only projects that will be completed remain. In this paper we evaluate the decision to build new generation facilities in a changing and uncertain regulatory environment. We estimate hazard rates for new power plant projects using a database of generation projects in North America and examine in greater detail the development patterns in California and Texas, two states with very different regulatory regimes. We find that regulatory uncertainty significantly affects the pattern of development in the electric power generation industry.  相似文献   
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Dendritic cells (DCs) can be divided by lineage into myeloid dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs). They both are present in mucosal tissues and regulate the immune response by secreting chemokines and cytokines. Inflammatory bowel diseases (IBDs) are characterized by a leaky intestinal barrier and the consequent translocation of bacterial lipopolysaccharide (LPS) to the basolateral side. This results in DCs activation, but the response of pDCs is still poorly characterized. In the present study, we compared mDCs and pDCs responses to LPS administration. We present a broad panel of DCs secreted factors, including cytokines, chemokines, and growth factors. Our recent studies demonstrated the anti-inflammatory effects of quercetin administration, but to date, there is no evidence about quercetin’s effects on pDCs. The results of the present study demonstrate that pDCs can respond to LPS and that quercetin exposure modulates soluble factors release through the same molecular pathway used by mDCs (Slpi, Hmox1, and AP-1).  相似文献   
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During social gatherings or emergency situations, infrastructure-based communication networks have difficulty operating given either increased traffic demand or possible damage. Nevertheless, current communication networks still rely on centralized networking paradigms. The adoption of a peer-to-peer communication paradigm would be better adapted to these needs, especially if it relies on the mobile phones that people normally carry, since they are automatically distributed where the communication needs are. However a question arises: can the spatio-temporal distribution of mobile phones enable a partially-connected ad hoc network that allows emergency communications to happen with an acceptable delay? To try to answer this question, we defined a methodology composed of three steps. First, the positions of seven hundred humans, spread over a metropolitan area, have been anonymously traced during a special gathering event. Then, with a multi-disciplinary approach, we have inferred the contact events from the humans’ traces. Finally, we have assessed the effectiveness of an ad hoc network established by the mobile phones to disseminate emergency information to the population in a timely fashion. The results reveal that the humans’ mobility can effectively enable emergency communications among a significant subset of mobile phones, although the connectivity of the network strictly depends on the number of cooperating devices and on the maximum allowed delay.  相似文献   
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N‐[2‐Methyl‐5‐(triazol‐1‐yl)phenyl]pyrimidin‐2‐amine derivatives were synthesized and evaluated in vitro for their potential use as inhibitors of Bcr‐Abl. The design is based on the bioisosterism between the 1,2,3‐triazole ring and the amide group. The synthesis involves a copper(I)‐catalyzed azide–alkyne cycloaddition (CuAAC) as the key step, with the exclusive production of anti‐(1,4)‐triazole derivatives. One of the compounds obtained shows general activity similar to that of imatinib; in particular, it was observed to be more effective in decreasing the fundamental function of cdc25A phosphatases in the K‐562 cell line.  相似文献   
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In the last few years, several efforts have been made to identify original strategies against glioblastoma multiforme (GBM): this requires a more detailed investigation of the molecular mechanism of GBM so that novel targets can be identified for new possible therapeutic agents. Here, using a combined biochemical and proteomic approach, we evaluated the ability of a blood–brain barrier-permeable 2,3-benzodiazepin-4-one, called 1g, to interfere with the activity and the expression of brain glycogen phosphorylase (PYGB) on U87MG cell line in parallel with the capability of this compound to inhibit the cell growth and cycle. Thus, our results highlighted PYGB as a potential therapeutic target in GBM prompting 1g as a capable anticancer drug thanks to its ability to negatively modulate the uptake and metabolism of glucose, the so-called “Warburg effect”, whose increase is considered a common feature of cancer cells in respect of their normal counterparts.  相似文献   
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Autoimmune-rheumatological diseases are worldwide distributed disorders and represent a complex array of illnesses characterized by autoreactivity (reactivity against self-antigens) of T-B lymphocytes and by the synthesis of autoantibodies crucial for diagnosis (biomarkers). Yet, the effects of the autoimmune chronic inflammation on the infiltrated tissues and organs generally lead to profound tissue and organ damage with loss of function (i.e., lung, kidney, joints, exocrine glands). Although progresses have been made on the knowledge of these disorders, much still remains to be investigated on their pathogenesis and identification of new biomarkers useful in clinical practice. The rationale of using proteomics in autoimmune-rheumatological diseases has been the unmet need to collect, from biological fluids that are easily obtainable, a summary of the final biochemical events that represent the effects of the interplay between immune cells, mesenchymal cells and endothelial cells. Proteomic analysis of these fluids shows encouraging results and in this review, we addressed four major autoimmune-rheumatological diseases investigated through proteomic techniques and provide evidence-based data on the highlights obtained in systemic sclerosis, primary and secondary Sjogren's syndrome, systemic lupus erythematosus and rheumatoid arthritis.  相似文献   
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The aim of this study was to compare the patterns of cerebellar alterations associated with bipolar disease with those induced by the presence of cerebellar neurodegenerative pathologies to clarify the potential cerebellar contribution to bipolar affective disturbance. Twenty-nine patients affected by bipolar disorder, 32 subjects affected by cerebellar neurodegenerative pathologies, and 37 age-matched healthy subjects underwent a 3T MRI protocol. A voxel-based morphometry analysis was used to show similarities and differences in cerebellar grey matter (GM) loss between the groups. We found a pattern of GM cerebellar alterations in both bipolar and cerebellar groups that involved the anterior and posterior cerebellar regions (p = 0.05). The direct comparison between bipolar and cerebellar patients demonstrated a significant difference in GM loss in cerebellar neurodegenerative patients in the bilateral anterior and posterior motor cerebellar regions, such as lobules I−IV, V, VI, VIIIa, VIIIb, IX, VIIb and vermis VI, while a pattern of overlapping GM loss was evident in right lobule V, right crus I and bilateral crus II. Our findings showed, for the first time, common and different alteration patterns of specific cerebellar lobules in bipolar and neurodegenerative cerebellar patients, which allowed us to hypothesize a cerebellar role in the cognitive and mood dysregulation symptoms that characterize bipolar disorder.  相似文献   
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