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Consider a monopolistic vendor who faces a known demand curve. By setting a price that equates marginal revenue with marginal cost, the vendor will maximize his profit. This logic holds true of both physical and digital goods. But since digitization will lower the variable production cost, it will strictly increase the profit to the vendor. Then, can we conclude that digitization always improves the vendor’s profitability? Not necessarily. Now consider what will happen on the next day of the sales. Facing deterministic demand, the physical goods vendor must have prepared the exact quantity of the product to sell, and thus all products are sold out. By contrast, the digital goods vendor will have no stock out, thanks to the nature of the digital good. Therefore, the rational vendor will try to sell more and achieve a higher profit after the sales date. To this end, the vendor will now lower the price to attract additional customers with lower reservation prices. The process will indefinitely continue. Knowing this would happen, customers will wait for the price reduction. Even the customers who would have purchased on the first day would defer the purchase until price gets lower. The digital goods vendor will anticipate this and accordingly lower the price on the first day and later, thereby compromising his profitability. Note that this downward spiral takes place as a result of digitization. Thus, digitization may not necessarily improve the profitability to the vendor. We develop an economic model to formally analyze the impact of digitization on the profitability to the vendor.

Natal dispersal likely plays an important role in avoiding inbreeding among large carnivores. We tested the hypothesis that male-biased dispersal reduces close inbreeding by limiting the spatial overlap of opposite-sex pairs of close relatives in brown bears (Ursus arctos) in the Shiretoko Peninsula, Hokkaido, Japan. We genotyped 837 individuals collected in 1998–2017 at 21 microsatellite loci and performed parentage analysis. To calculate natal dispersal distance, we considered the site where the mother was identified as the birthplace of her offspring, and the site where the offspring were identified as their dispersed place. As predicted, we found that dispersal distances were significantly greater for males (12.4 km ± 1.0) than for females (7.7 km ± 0.9), and those for males increased from 3 years old, indicating that males begin to disperse around the time sexual maturation begins. Relatedness decreased with distance among pairs of females, and the mean relatedness was significantly higher between pairs of females than between pairs of males or between female–male pairs within 3 km. Closely related female–male pairs rarely (5–6%) resided in close proximity (< 3 km), compared with pairs of closely related females. Our study revealed that the potential for close inbreeding was low in Hokkaido brown bears because males are effective dispersers.

Knowing the reproductive characteristics of a species is essential for the appropriate conservation and management of wildlife. In this study, we investigated the demographic parameters, including age of primiparity, litter size, inter-birth interval, reproductive rate, and cub survival rate, of Hokkaido brown bears (Ursus arctos yesoensis) in the Rusha area on the Shiretoko Peninsula, Hokkaido, Japan, based on a long-term, individual-based monitoring survey. A total of 15 philopatric females were observed nearly every year from 2006 to 2016, and these observations were used to estimate reproductive parameters. The mean age of primiparity was 5.3 ± 0.2 (SE) years (n = 7, 95% CI = 5.0-5.6). We observed 81 cubs in 46 litters from 15 bears. Litter size ranged from one to three cubs, and averaged 1.76 ± 0.08 (SE) cubs/litter (95% CI = 1.61-1.91). Inter-birth intervals ranged from 1 to 4 years, and the mean value was estimated as 2.43 (95% CI = 2.16-2.76) and 2.53 (95% CI = 2.26-2.85) years in all litters and in litters that survived at least their first year, respectively. The reproductive rate was estimated from 0.70 to 0.76 young born/year/reproductive adult female, depending on the method of calculation. The cub survival rate between 0.5 and 1.5 years ranged from 60 to 73%. Most cub disappearances occurred in July and August, suggesting that cub mortality is mainly due to poor nutrition in the summer. All reproductive parameters observed in the Rusha area on the Shiretoko Peninsula fell within the range reported in Europe and North America, and were among the lowest or shortest age of primiparity, litter size, and inter-birth intervals, and ranked at a high level for reproductive rate.

Understanding natal dispersal patterns is fundamental in the ecology and conservation biology of large wild carnivores. In this study, we used two approaches to determine genetic variation and dispersal patterns of brown bears in the Shiretoko Peninsula, eastern Hokkaido, Japan. The first approach was a large-scale genetic analysis. We analyzed haplotypes from the mitochondrial DNA (mtDNA) control region of 760 individual samples collected throughout the peninsula during 1998–2016. We detected seven haplotypes, including two that were confirmed for the first time. In females, the distribution of haplotypes was geographically structured, whereas haplotypes in males were distributed widely throughout the peninsula. Only some males in the lower peninsula had haplotypes that were not detected within the peninsula. The second approach was a local-scale genetic analysis, including intensive focal sampling in the Rusha area, a special wildlife protection area on the peninsula. Proportions of mtDNA haplotypes in adult bears were investigated and compared between the sexes. Although more than half of the females had the same haplotype, males had more diverse haplotypes, suggesting that they came to the Rusha area from other regions. Thus, our study revealed that mtDNA haplotype distribution has been maintained by female philopatry, and that bears exhibit male-biased dispersal. Furthermore, the lower peninsula appears to act as a contact zone between the peninsula and mainland Hokkaido, which is important for maintaining genetic diversity.

A tariff is the total charge payable by a customer for services provided. We study the design of tariffs for a telecommunications service provider. We develop an economic model that captures the negative externalities of the network and the diversity of customers. The tariff is designed so that it reflects the expected response of different customers and the system congestion it would induce. We study a simple tariff structure in wide use by mobile phone carriers—a menu of \"fixed-up-to (FUT)\" plans like \"fixed access fee $35 up to 300 minutes, and $0.40 per minute beyond the limit.\" We derive the optimal menu of FUT plans and show that such a simple FUT menu structure delivers as good performance to the monopolistic carrier as any nonlinear pricing schedule.

We consider a game theoretic congestion model with parallel nodes and homogeneous customers. The purpose of this paper is to examine how the priority passes improve social welfare for such a system. To this end, we prove the existence of an equilibrium. The system with no priority pass has a unique equilibrium. With the introduction of priority passes, the uniqueness of the equilibrium may be destroyed. We provide a sufficient condition under which the system with priority passes outperforms the system with no priority passes. The problem is explored numerically as well.

Consider a data communication network owned and operated by a single organization. The network has an infinite number of small users and is managed by a system manager (SM) whose objective is to maximize the net value of the system as a whole. The objective of this paper is to study pricing mechanisms that induce the optimal arrival rates when the SM has no full knowledge of the demand in advance. We investigate the system behavior under three alternative dynamic pricing rules and users' expectations models, and characterize the equilibrium and its stability conditions.

Although DNA double-strand break (DSB) repair is mediated by numerous proteins accumulated at DSB sites, how DNA repair proteins are assembled into damaged chromatin has not been fully elucidated. Here we show that a member of the tripartite motif protein family, TRIM29, is a histone-binding protein responsible for DNA damage response (DDR). We found that TRIM29 interacts with BRCA1-associated surveillance complex, cohesion, DNA-PKcs and components of TIP60 complex. The dynamics of the TRIM29-containing complex on H2AX nucleosomes is coordinated by a cross-talk between histone modifications. TRIM29 binds to modified histone H3 and H4 tails in the context of nucleosomes. Furthermore, chromatin binding of TRIM29 is required for the phosphorylation of H2AX and cell viability in response to ionizing radiation. Our results suggest that TRIM29 functions as a scaffold protein to assemble DNA repair proteins into chromatin followed by efficient activation of DDR. Many proteins are assembled into damaged chromatins to repair DNA double-strand breaks (DSBs). Here, the authors show that TRIM29 binds to modified histone H3 and H4 tails following DSB formation and functions as a scaffold protein to assemble DNA repair proteins into chromatin.

Bottleneck analysis is a useful tool in capacity planning for centrally controlled network systems. However, under a decentralized network where individual users are allowed to select their own routes, straightforward application of bottleneck analysis does not necessarily yield an optimal performance. It may even hurt the system performance—an aspect of Braess's paradox. We investigate the capacity expansion problem for a decentralized system with general network topology. To this end, we first discuss the short-run problem and show that the externality pricing solves the joint problem of demand and routing control. We then study the capacity expansion/reduction problem for decentralized systems that may or may not be optimally controlled in the short run.

Metastasis is a major cause of death in cancer patients and involves a multistep process including detachment of cancer cells from a primary cancer, invasion of surrounding tissue, spread through circulation, re-invasion and proliferation in distant organs. KiSS-1 is a human metastasis suppressor gene 1 , that suppresses metastases of human melanomas 2 and breast carcinomas 3 without affecting tumorigenicity. However, its gene product and functional mechanisms have not been elucidated. Here we show that KiSS-1 (refs 1 , 4 ) encodes a carboxy-terminally amidated peptide with 54 amino-acid residues, which we have isolated from human placenta as the endogenous ligand of an orphan G-protein-coupled receptor (hOT7T175) and have named ‘metastin’. Metastin inhibits chemotaxis and invasion of hOT7T175-transfected CHO cells in vitro and attenuates pulmonary metastasis of hOT7T175-transfected B16-BL6 melanomas in vivo . The results suggest possible mechanisms of action for KiSS-1 and a potential new therapeutic approach.