Peak-Hour Pricing Under Negative Externality: Impact of Customer Flexibility and Competitive Asymmetry

Several industries that provide services to customers (e.g., public utility and transportation) charge higher prices during peak hours to smooth demand. With technologies (e.g., electronic shelf labels) enabling retailers to change prices easily within each day, should supermarkets use peak-hour pricing? To examine this question formally, we introduce a stylized duopoly model in the presence of “negative externality,” where firms compete for congestion-averse customers. We characterize how customers endogenously segment themselves regarding when and where to shop, and then use the equilibrium outcomes to examine whether the firms should implement peak-hour pricing for varying types of customer flexibility and competitive asymmetry. Our analysis shows that, if customers are not flexible in their store choice, then both firms would always use peak-hour pricing. However, if store choice flexibility is present, then firms’ decisions depend on the competitive asymmetry as follows. If one firm has a clear competitive advantage (in terms of value or price) over the other firm, then the dominant firm will use peak-hour pricing, whereas the other firm will not. Otherwise, both firms will use peak-hour pricing if they engage in symmetric competition (in terms of similar value and price), or neither firm will use it if they engage in differentiated competition (high value versus low cost). Through our analysis of different extensions, we find that a firm’s ability to set its regular price would dampen the effect of peak-period pricing. Also, we obtain consistent results when there is heterogeneity in customer valuation and customer congestion aversion level

Hypertonic saline increases lung epithelial lining fluid glutathione and thiocyanate: two protective CFTR-dependent thiols against oxidative injury

<p>Abstract</p> <p>Background</p> <p>Cystic fibrosis is a debilitating lung disease due to mutations in the cystic fibrosis transmembrane conductance regulator protein (CFTR) and is associated with chronic infections resulting in elevated myeloperoxidase activity and generation of hypochlorous acid (HOCl). CFTR mutations lead to decreased levels of glutathione (GSH) and thiocyanate (SCN) in the epithelial lining fluid (ELF). Hypertonic saline is used to improve lung function however the mechanism is uncertain.</p> <p>Methods</p> <p>In the present study, the effect of GSH and SCN on HOCl-mediated cell injury and their changes in the ELF after hypertonic saline nebulization in wild type (WT) and CFTR KO mice was examined. CFTR sufficient and deficient lung cells were assessed for GSH, SCN and corresponding sensitivity towards HOCl-mediated injury, in vitro.</p> <p>Results</p> <p>CFTR (-) cells had lower extracellular levels of both GSH and SCN and were more sensitive to HOCl-mediated injury. In vivo, hypertonic saline increased ELF GSH in the WT and to a lesser extent in the CFTR KO mice but only SCN in the WT ELF. Finally, potential protective effects of GSH and SCN at concentrations found in the ELF against HOCl toxicity were examined in vitro.</p> <p>Conclusions</p> <p>While the concentrations of GSH and SCN associated with the WT ELF protect against HOCl toxicity, those found in the CFTR KO mice were less sufficient to inhibit cell injury. These data suggests that CFTR has important roles in exporting GSH and SCN which are protective against oxidants and that hypertonic saline treatment may have beneficial effects by increasing their levels in the lung.</p

DJ-1 interacts with and regulates paraoxonase-2, an enzyme critical for neuronal survival in response to oxidative stress.

Loss-of-function mutations in DJ-1 (PARK7) gene account for about 1% of all familial Parkinson's disease (PD). While its physiological function(s) are not completely clear, DJ-1 protects neurons against oxidative stress in both in vitro and in vivo models of PD. The molecular mechanism(s) through which DJ-1 alleviates oxidative stress-mediated damage remains elusive. In this study, we identified Paraoxonase-2 (PON2) as an interacting target of DJ-1. PON2 activity is elevated in response to oxidative stress and DJ-1 is crucial for this response. Importantly, we showed that PON2 deficiency hypersensitizes neurons to oxidative stress induced by MPP+ (1-methyl-4-phenylpyridinium). Conversely, over-expression of PON2 protects neurons in this death paradigm. Interestingly, PON2 effectively rescues DJ-1 deficiency-mediated hypersensitivity to oxidative stress. Taken together, our data suggest a model by which DJ-1 exerts its antioxidant activities, at least partly through regulation of PON2

MAPK-Dependent Regulation of IL-1-and β-Adrenoreceptor-Induced Inflammatory Cytokine Production From Mast Cells: Implications for the Stress Response

Background: Catecholamines, such as epinephrine, are elaborated in stress responses, and mediate vasoconstriction to cause elevation in systemic vascular resistance and blood pressure. Our previous study has shown that IL-1 can induce mast cells to produce proinflammatory cytokines which are involved in atherogenesis. The aim of this study was to determine the effects of epinephrine on IL-1-induced proatherogenic cytokine production from mast cells. Results: Two ml of HMC-1 (0.75 × 106 cells/ml) were cultured with epinephrine (1 × 10-5 M) in the presence or absence of IL-1β (10 ng/ml) for 24 hrs. HMC-1 cultured alone produced none to trace amounts of IL-6, IL-8, and IL-13. IL-1β significantly induced production of these cytokines in HMC-1, while epinephrine alone did not. However, IL-6, IL-8, and IL-13 production induced by IL-1β were significantly enhanced by addition of epinephrine. The enhancing effect appears to involve NF-κB and p38 MAPK pathways. Flow cytometry showed the presence of β1 and β2 adrenoreceptors on resting mast cells. The enhancing effect of proatherogenic cytokine production by epinephrine was down regulated by the β1 and β2 adrenoceptor antagonist, propranolol, but not by the β1 adrenoceptor antagonist, atenolol, suggesting the effect involved β2 adrenoceptors. The enhancing effect of epinephrine on proatherogenic cytokine production was also down regulated by the immunosuppressive drug, dexamethasone. Conclusions: These results not only confirm that an acute phase cytokine, IL-1β, regulates mast cell function, but also show that epinephrine up regulates the IL-1β induction of proatherogenic cytokines in mast cells. These data provide a novel role for epinephrine, a stress hormone, in inflammation and atherogenesis

Spatially Continuous Strain Monitoring using Distributed Fiber Optic Sensors Embedded in Carbon Fiber Composites

A distributed fiber optic strain sensor based on Rayleigh backscattering, embedded in a fiber-reinforced polymer composite, has been demonstrated. The optical frequency domain reflectometry technique is used to analyze the backscattered signal. The shift in the Rayleigh backscattered spectrum is observed to be linearly related to the change in strain of the composite material. The sensor (standard single-mode fiber) is embedded between the layers of the composite laminate. A series of tensile loads is applied to the laminate using an Instron testing machine, and the corresponding strain distribution of the laminate is measured. The results show a linear response indicating a seamless integration of the optical fiber in the composite material and a good correlation with the electrical-resistance strain gauge results. The sensor is also used to evaluate the strain response of a composite-laminate-based cantilever beam. Distributed strain measurements in a composite laminate are successfully obtained using an embedded fiber optic sensor

Identification of Evening Complex Associated Proteins in Arabidopsis by Affinity Purification and Mass Spectrometry

Many species possess an endogenous circadian clock to synchronize internal physiology with an oscillating external environment. In plants, the circadian clock coordinates growth, metabolism and development over daily and seasonal time scales. Many proteins in the circadian network form oscillating complexes that temporally regulate myriad processes, including signal transduction, transcription, protein degradation and post-translational modification. In Arabidopsis thaliana, a tripartite complex composed of EARLY FLOWERING 4 (ELF4), EARLY FLOWERING 3 (ELF3), and LUX ARRHYTHMO (LUX), named the evening complex, modulates daily rhythms in gene expression and growth through transcriptional regulation. However, little is known about the physical interactions that connect the circadian system to other pathways. We used affinity purification and mass spectrometry (AP-MS) methods to identify proteins that associate with the evening complex in A. thaliana. New connections within the circadian network as well as to light signaling pathways were identified, including linkages between the evening complex, TIMING OF CAB EXPRESSION1 (TOC1), TIME FOR COFFEE (TIC), all phytochromes and TANDEM ZINC KNUCKLE/PLUS3 (TZP). Coupling genetic mutation with affinity purifications tested the roles of phytochrome B (phyB), EARLY FLOWERING 4, and EARLY FLOWERING 3 as nodes connecting the evening complex to clock and light signaling pathways. These experiments establish a hierarchical association between pathways and indicate direct and indirect interactions. Specifically, the results suggested that EARLY FLOWERING 3 and phytochrome B act as hubs connecting the clock and red light signaling pathways. Finally, we characterized a clade of associated nuclear kinases that regulate circadian rhythms, growth, and flowering in A. thaliana. Coupling mass spectrometry and genetics is a powerful method to rapidly and directly identify novel components and connections within and between complex signaling pathways

Microstructural and mechanical characterisation of Fe-14Cr-0.22Hf alloy fabricated by spark plasma sintering

Fe-14Cr pre-alloyed powder and pure Hf powder were mechanically alloyed to produce powder with nominal composition Fe-14Cr-0.22Hf (wt. %) that was consolidated by the spark plasma sintering (SPS) technique in order to investigate the ability of Hf to produce a nanometric dispersion of oxide particles in a ferritic matrix. Comprehensive microstructural and mechanical characterisation of the as-milled powder and the consolidated material was performed using electron microscopy, X-ray diffraction, atom probe tomography and indentation techniques. It was shown that Hf additions can effectively produce, by internal oxidation, a fine scale dispersion of Hf-O nanoparticles in the consolidated material. A uniform grain structure was produced in the alloy. Although the nanoparticle dispersion was not homogeneous at the finest scale, the resulting dispersion strengthening contributed significantly to the hardness. According to these results, internal oxidation of reactive elements rather than direct addition of oxides may offer additional opportunities in the design and development of oxide dispersion strengthened steels