649 research outputs found

    Demand Side Load Management for Big Industrial Energy Users under Blockchain-Based Peer-to-Peer Electricity Market

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    Β© 2010-2012 IEEE. Blockchain is the key technology of Bitcoin and other cryptocurrencies, and it is one of the most exciting technologies changing the world as of late. Targeting at big industrial energy users, this paper first presents a new market structure (i.e., transaction rules) under existing blockchain-based electricity transaction platforms to cover popular types of markets such as contract, day-ahead, adjustment and balancing markets; and then focuses on the optimal load management problem for a particular industrial user. The proof-of-work cost from blockchain is also modeled. A key feature of this load management problem is that the user has direct control on its own load. The obtained load control model is much more accurate than existing approaches in which system operators or demand aggregators cannot control load directly and have to rely on inaccurate estimations. As a case study, the pumping load of a water supply plant is investigated to illustrate how the demand load is managed under this blockchain-based market. From the case study, it is found that 18.9% of total cost can be saved under this new market structure

    A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries

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    Neural stem cells are activated within neurogenic niches in response to brain injuries. This results in the production of neuroblasts, which unsuccessfully attempt to migrate toward the damaged tissue. Injuries constitute a gliogenic/non-neurogenic niche generated by the presence of anti-neurogenic signals, which impair neuronal differentiation and migration. Kinases of the protein kinase C (PKC) family mediate the release of growth factors that participate in different steps of the neurogenic process, particularly, novel PKC isozymes facilitate the release of the neurogenic growth factor neuregulin. We have demonstrated herein that a plant derived diterpene, (EOF2; CAS number 2230806-06-9), with the capacity to activate PKC facilitates the release of neuregulin 1, and promotes neuroblasts differentiation and survival in cultures of subventricular zone (SVZ) isolated cells in a novel PKC dependent manner. Local infusion of this compound in mechanical cortical injuries induces neuroblast enrichment within the perilesional area, and noninvasive intranasal administration of EOF2 promotes migration of neuroblasts from the SVZ towards the injury, allowing their survival and differentiation into mature neurons, being some of them cholinergic and GABAergic. Our results elucidate the mechanism of EOF2 promoting neurogenesis in injuries and highlight the role of novel PKC isozymes as targets in brain injury regeneration

    Infrequent Detection of KI, WU and MC Polyomaviruses in Immunosuppressed Individuals with or without Progressive Multifocal Leukoencephalopathy

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    Conflicting prevalence of newly identified KI(KIPyV), WU(WUPyV) and Merkel Cell Carcinoma(MCPyV) polyomaviruses have been reported in progressive multifocal leukoencephalopathy(PML) patient samples, ranging from 0 to 14.3%. We analyzed the prevalence of these polyomaviruses in cerebrospinal fluid(CSF), peripheral blood mononuclear cells(PBMC), and bone marrow samples from PML patients, immunosuppressed individuals with or without HIV, and multiple sclerosis(MS) patients. Distinct PCR tests for KIPyV, WUPyV and MCPyV DNA performed in two independent laboratories detected low levels of MCPyV DNA only in 1/269 samples. The infrequent detections of these viruses in multiple samples from immunosuppressed individuals including those with PML suggest that their reactivation mechanisms may be different from that of JC polyomavirus (JCPyV) and that they do not play a role in the pathogenesis of PML

    A Disintegrin and Metalloenzyme (ADAM) 17 Activation Is Regulated by Ξ±5Ξ²1 Integrin in Kidney Mesangial Cells

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    The disintegrin and metalloenzyme ADAM17 participates in numerous inflammatory and proliferative diseases, and its pathophysiological role was implicated in kidney fibrosis, polycystic kidney disease and other chronic kidney diseases. At present, we have little understanding how the enzyme activity is regulated. In this study we wanted to characterize the role of Ξ±5Ξ²1 integrin in ADAM17 activity regulation during G protein-coupled receptor (GPCR) stimulation.We showed previously that the profibrotic GPCR agonist serotonin (5-HT) induced kidney mesangial cell proliferation through ADAM17 activation and heparin-binding epidermal growth factor (HB-EGF) shedding. In the present studies we observed that in unstimulated mesangial cell lysates Ξ±5Ξ²1 integrin co-precipitated with ADAM17 and that 5-HT treatment of the cells induced dissociation of Ξ±5Ξ²1 integrin from ADAM17. Using fluorescence immunostaining and in situ proximity ligation assay, we identified the perinuclear region as the localization of the ADAM17/Ξ±5Ξ²1 integrin interaction. In cell-free assays, we showed that purified Ξ±5Ξ²1 integrin and Ξ²1 integrin dose-dependently bound to and inhibited activity of recombinant ADAM17. We provided evidence that the conformation of the integrin determines its ADAM17-binding ability. To study the effect of Ξ²1 integrin on ADAM17 sheddase activity, we employed alkaline phosphatase-tagged HB-EGF. Overexpression of Ξ²1 integrin lead to complete inhibition of 5-HT-induced HB-EGF shedding and silencing Ξ²1 integrin by siRNA significantly increased mesangial cells ADAM17 responsiveness to 5-HT.Our data show for the first time that Ξ²1 integrin has an important physiological role in ADAM17 activity regulation. We suggest that regulating Ξ±5Ξ²1 integrin binding to ADAM17 could be an attractive therapeutic target in chronic kidney diseases

    Anthrax Toxins Induce Shock in Rats by Depressed Cardiac Ventricular Function

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    Anthrax infections are frequently associated with severe and often irreversible hypotensive shock. The isolated toxic proteins of Bacillus anthracis produce a non-cytokine-mediated hypotension in rats by unknown mechanisms. These observations suggest the anthrax toxins have direct cardiovascular effects. Here, we characterize these effects. As a first step, we administered systemically anthrax lethal toxin (LeTx) and edema toxin (EdTx) to cohorts of three to twelve rats at different doses and determined the time of onset, degree of hypotension and mortality. We measured serum concentrations of the protective antigen (PA) toxin component at various time points after infusion. Peak serum levels of PA were in the Β΅g/mL range with half-lives of 10–20 minutes. With doses that produced hypotension with delayed lethality, we then gave bolus intravenous infusions of toxins to groups of four to six instrumented rats and continuously monitored blood pressure by telemetry. Finally, the same doses used in the telemetry experiments were given to additional groups of four rats, and echocardiography was performed pretreatment and one, two, three and twenty-four hours post-treatment. LeTx and EdTx each produced hypotension. We observed a doubling of the velocity of propagation and 20% increases in left ventricular diastolic and systolic areas in LeTx-treated rats, but not in EdTx-treated rats. EdTx-but not LeTx-treated rats showed a significant increase in heart rate. These results indicate that LeTx reduced left ventricular systolic function and EdTx reduced preload. Uptake of toxins occurs readily into tissues with biological effects occurring within minutes to hours of serum toxin concentrations in the Β΅g/mL range. LeTx and EdTx yield an irreversible shock with subsequent death. These findings should provide a basis for the rational design of drug interventions to reduce the dismal prognosis of systemic anthrax infections

    Epstein-Barr Virus-Induced Gene 3 (EBI3): A Novel Diagnosis Marker in Burkitt Lymphoma and Diffuse Large B-Cell Lymphoma

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    The distinction between Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), two types of mature aggressive B-cell lymphomas that require distinct treatments, can be difficult because of forms showing features intermediate between DLBCL and BLΒ (here called BL/DLBCL). They can be discriminated by the presence of c-myc translocations characteristic of BL. However, these are not exclusive of BL and when present in DLBCL are associated with lower survival. In this study, we show that Epstein-Barr virus-induced gene 3 (EBI3) is differentially expressed among BL and DLBCL. Analysis of gene expression data from 502 cases of aggressive mature B-cell lymphomas available on Gene Expression Omnibus and immunohistochemical analysis of 184 cases of BL, BL/DLBCL or DLBCL, showed that EBI3 was not expressed in EBV-positive or -negative BL cases, whereas it was expressed by over 30% of tumoral cells in nearly 80% of DLBCL cases, independently of their subtypes. In addition, we show that c-myc overexpression represses EBI3 expression, and that DLBCL or BL/DLBCL cases with c-myc translocations have lower expression of EBI3. Thus, EBI3 immunohistochemistry could be useful to discriminate BL from DLBCL, and to identify cases of BL/DLBCL or DLBCL with potential c-myc translocations

    Alteration of Striatal Dopaminergic Neurotransmission in a Mouse Model of DYT11 Myoclonus-Dystonia

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    Background: DYT11 myoclonus-dystonia (M-D) syndrome is a neurological movement disorder characterized by myoclonic jerks and dystonic postures or movement that can be alleviated by alcohol. It is caused by mutations in SGCE encoding e-sarcoglycan (e-SG); the mouse homolog of this gene is Sgce. Paternally-inherited Sgce heterozygous knockout (Sgce KO) mice exhibit myoclonus, motor impairment and anxiety- and depression-like behaviors, modeling several clinical symptoms observed in DYT11 M-D patients. The behavioral deficits are accompanied by abnormally high levels of dopamine and its metabolites in the striatum of Sgce KO mice. Neuroimaging studies of DYT11 M-D patients show reduced dopamine D2 receptor (D2R) availability, although the possibility of increased endogenous dopamine, and consequently, competitive D2R occupancy cannot be ruled out. Methodology/Principal Findings: The protein levels of striatal D2R, dopamine transporter (DAT), and dopamine D1 receptor (D1R) in Sgce KO mice were analyzed by Western blot. The striatal dopamine release after amphetamine injection in Sgce KO mice were analyzed by microdialysis in vivo. The striatal D2R was significantly decreased in Sgce KO mice without altering DAT and D1R. Sgce KO mice also exhibited a significant increase of dopamine release after amphetamine injection in comparison to wild-type (WT) littermates. Conclusion/Significance: The results suggest e-SG may have a role in the regulation of D2R expression. The loss of e-S
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