The Economics of All-You-Can-Read Pricing: Tariff Choice, Contract Renewal, and Switching for E-Book Purchases

E-book markets are currently moving through a period of disequilibrium as new pricing structures (i.e., flat-fee subscriptions) are rapidly embraced by major vendors. On the basis of a novel dataset, we investigate how the availability of “all-you-can-read” pricing programs influences consumers’ tariff choice, contract renewal, and switching behaviors. Consistent with the rational choice framework, the findings suggest that most e-book consumers significantly gain from subscription-based tariffs. However, we also find some other intriguing results. Among the three subscription designs examined, the 1-week plan affords consumers more economic benefits than do 1-day or 1-month programs. The economic gains derived from subscription-based tariffs diminish as consumers renew their subscriptions under the same contract duration. Consumers who switch to other plans also suffer from reduced savings. Finally, iOS users are more inclined to select subscription models than are Android users because of the absence of in-app purchase functionalities for the former

Imiquimod enhances excitability of dorsal root ganglion neurons by inhibiting background (K2P) and voltage-gated (Kv1.1 and Kv1.2) potassium channels

<p>Abstract</p> <p>Background</p> <p>Imiquimod (IQ) is known as an agonist of Toll-like receptor 7 (TLR7) and is widely used to treat various infectious skin diseases. However, it causes severe itching sensation as its side effect. The precise mechanism of how IQ causes itching sensation is unknown. A recent report suggested a molecular target of IQ as TLR7 expressed in dorsal root ganglion (DRG) neurons. However, we recently proposed a TLR7-independent mechanism, in which the activation of TLR7 is not required for the action of IQ in DRG neurons. To resolve this controversy regarding the involvement of TLR7 and to address the exact molecular identity of itching sensation by IQ, we investigated the possible molecular target of IQ in DRG neurons.</p> <p>Findings</p> <p>When IQ was applied to DRG neurons, we observed an increase in action potential (AP) duration and membrane resistance both in wild type and TLR7-deficient mice. Based on these results, we tested whether the treatment of IQ has an effect on the activity of K⁺channels, K_v1.1 and K_v1.2 (voltage-gated K⁺channels) and TREK1 and TRAAK (K_2Pchannels). IQ effectively reduced the currents mediated by both K⁺channels in a dose-dependent manner, acting as an antagonist at TREK1 and TRAAK and as a partial antagonist at K_v1.1 and K_v1.2.</p> <p>Conclusions</p> <p>Our results demonstrate that IQ blocks the voltage-gated K⁺channels to increase AP duration and K_2Pchannels to increase membrane resistance, which are critical for the membrane excitability of DRG neurons. Therefore, we propose that IQ enhances the excitability of DRG neurons by blocking multiple potassium channels and causing pruritus.</p

Long-term prenatal stress increases susceptibility of N-methyl-D-aspartic acid-induced spasms in infant rats

PurposeInfantile spasms, also known as West syndrome, is an age-specific epileptic seizure. Most patients with this condition also exhibit delayed development. This study aimed to determine the effect of long-term prenatal stress on susceptibility to infantile spasms.MethodsWe subjected pregnant rats to acute or chronic immobilization stress. Resulting offspring received N-methyl-D-aspartic acid (15 mg/kg, intraperitoneally) on postnatal day 15, and their behaviors were observed 75 minutes after injection. The expression of KCC2 and GAD67 was also determined using immunohistochemistry.ResultsExposure to long-term prenatal stress increased the frequency of spasms and decreased the latency to onset of spasms compared with offspring exposed to short-term prenatal stress. Expression of KCC2 and GAD67 also decreased in the group exposed to long-term prenatal stress compared with the group exposed to short-term prenatal stress.ConclusionOur study suggests that exposure to long-term prenatal stress results in increased susceptibility to seizures

Surface energy-mediated construction of anisotropic semiconductor wires with selective crystallographic polarity.

ZnO is a wide band-gap semiconductor with piezoelectric properties suitable for opto-electronics, sensors, and as an electrode material. Controlling the shape and crystallography of any semiconducting nanomaterial is a key step towards extending their use in applications. Whilst anisotropic ZnO wires have been routinely fabricated, precise control over the specific surface facets and tailoring of polar and non-polar growth directions still requires significant refinement. Manipulating the surface energy of crystal facets is a generic approach for the rational design and growth of one-dimensional (1D) building blocks. Although the surface energy is one basic factor for governing crystal nucleation and growth of anisotropic 1D structures, structural control based on surface energy minimization has not been yet demonstrated. Here, we report an electronic configuration scheme to rationally modulate surface electrostatic energies for crystallographic-selective growth of ZnO wires. The facets and orientations of ZnO wires are transformed between hexagonal and rectangular/diamond cross-sections with polar and non-polar growth directions, exhibiting different optical and piezoelectrical properties. Our novel synthetic route for ZnO wire fabrication provides new opportunities for future opto-electronics, piezoelectronics, and electronics, with new topological properties

TLR2-induced astrocyte MMP9 activation compromises the blood brain barrier and exacerbates intracerebral hemorrhage in animal models

Background: The innate immune response plays an important role in the pathogenesis of intracerebral hemorrhage (ICH). Recent studies have shown that Toll-like receptor 2 (TLR2) is involved in the innate immune response in various neurological diseases, yet neither its role in ICH nor the mechanisms by which it functions have yet been elucidated. We examined these in this study using a collagenase-induced mouse ICH model with TLR2 knock-out (KO) mice. Results: TLR2 expression was upregulated in the ipsilateral hemorrhagic tissues of the collagenase-injected mice. Brain injury volume and neurological deficits following ICH were reduced in TLR2 KO mice compared to wild-type (WT) control mice. Heterologous blood-transfer experiments show that TLR2 signaling in brain-resident cells, but not leukocytes, contributes to the injury. In our study to elucidate underlying mechanisms, we found that damage to blood-brain barrier (BBB) integrity following ICH was attenuated in TLR2 KO mice compared to WT mice, which may be due to reduced matrix metalloproteinase-9 (MMP9) activation in astrocytes. The reduced BBB damage accompanies decreased neutrophil infiltration and proinflammatory gene expression in the injured brain parenchyma, which may account for the attenuated brain damage in TLR2 KO mice after ICH. Conclusions: TLR2 plays a detrimental role in ICH-induced brain damage by activating MMP9 in astrocytes, compromising BBB, and enhancing neutrophils infiltration and proinflammatory gene expression. © 2015 Min et al.; licensee BioMed Central.1