"Indirect Network Effects and the Product Cycle: Video Games in the U.S., 1994-2002"

This paper examines the importance of indirect network effects in the U.S.video game market between 1994 and 2002. The diffusion of game systems is analyzed by the interaction between console adoption decisions and software supply decisions. Estimation results suggest that introductory pricing is an effective practice at the beginning of the product cycle, and expanding software variety becomes more effective later. The paper also finds a degree of inertia in the software market that does not exist in the hardware market. This observation implies that software providers continue to exploit the installed base of hardware users after hardware demand has slowed.

Indirect Network Effects and the Product Cycle: Video Games in the U.S., 1994-2002

This paper examines the importance of indirect network effects in the U.S. video game market between 1994 and 2002. The diffusion of game systems is analyzed by the interaction between console adoption decisions and software supply decisions. Estimation results suggest that introductory pricing is an effective practice at the beginning of the product cycle, and expanding software variety becomes more effective later. The paper also finds a degree of inertia in the software market that does not exist in the hardware market. This observation implies that software providers continue to exploit the installed base of hardware users after hardware demand has slowed

Indirect Network Effects and the Product Cycle: Video Games in the U.S., 1994-2002

This paper examines the importance of indirect network effects in the U.S. video game market between 1994 and 2002. The diffusion of game systems is analyzed by the interaction between console adoption decisions and software supply decisions. Estimation results suggest that introductory pricing is an effective practice at the beginning of the product cycle, and expanding software variety becomes more effective later. The paper also finds a degree of inertia in the software market that does not exist in the hardware market. This observation implies that software providers continue to exploit the installed base of hardware users after hardware demand has slowed

Spatial analysis of hepatobiliary abnormalities in a population at high-risk of cholangiocarcinoma in Thailand

Cholangiocarcinoma (CCA) is a serious health challenge with low survival prognosis. The liver fluke, Opisthorchis viverrini, plays a role in the aetiology of CCA, through hepatobiliary abnormalities: liver mass (LM), bile duct dilation, and periductal fibrosis (PDF). A population-based CCA screening program, the Cholangiocarcinoma Screening and Care Program, operates in Northeast Thailand. Hepatobiliary abnormalities were identified through ultrasonography. A multivariate zero-inflated, Poisson regression model measured associations between hepatobiliary abnormalities and covariates including age, sex, distance to water resource, and history of O. viverrini infection. Geographic distribution was described using Bayesian spatial analysis methods. Hepatobiliary abnormality prevalence was 38.7%; highest in males aged > 60 years (39.8%). PDF was most prevalent (20.1% of males). The Standardized Morbidity Ratio (SMR) for hepatobiliary abnormalities was highest in the lower and upper parts of the Northeast region.Tis work was supported by Khon Kaen University through CASCAP (Grant no. CASCAP 1/60), the National Research Council of Tailand through the Medical Research Network of the Consortium of Tai Medical Schools (Grant no. MRF.59-076) and National Research Council of Tailand (NRCT/2559-134)

Airborne Observations of Carbon Dioxide and Methane Emission Ratios from the Yosemite Rim Wildfire, California

This paper presents airborne in situ measurements of carbon dioxide (CO2) and methane (CH4) downwind of an exceptionally large wildfire, the Rim Fire, near Yosemite, California, during two flights. Data analyses are discussed in terms of emission ratios (ER) and emission factors (EF) and are compared to previous studies. CH4 ERs were 7.5-7.9 parts per billion (ppb) CH4 for every 1 part per million (ppm) of CO2 (ppb CH4 (ppm CO2)(exp.-1)) on 29 August 2013 and 14.2-16.7 ppb CH4 (ppm CO2)(exp. -1) on 10 September 2013. This study measured only CO2 and CH4; however, estimated emission factors (EEFs) are used as rough estimates of EFs of CO2 and CH4 and are in close agreement with EFs reported in previous studies. In the western US, wildfires dominate over prescribed fires, contributing to atmospheric trace gas budgets and regional and local air pollution. Limited sampling of emissions from wildfires means western US emission estimates rely largely on data from prescribed fires, which may not be a suitable proxy for wildfire emissions. Given the magnitude of the Yosemite Rim wildfire, the impacts it had on regional air quality and the limited sampling of wildfire emissions in the western US to date, this study provides a valuable measurement dataset and may have important implications for forestry and regional air quality management

Transcriptional Activation of Low-Density Lipoprotein Receptor Gene by DJ-1 and Effect of DJ-1 on Cholesterol Homeostasis

DJ-1 is a novel oncogene and also causative gene for familial Parkinson’s disease park7. DJ-1 has multiple functions that include transcriptional regulation, anti-oxidative reaction and chaperone and mitochondrial regulation. For transcriptional regulation, DJ-1 acts as a coactivator that binds to various transcription factors, resulting in stimulation or repression of the expression of their target genes. In this study, we found the low-density lipoprotein receptor (LDLR) gene is a transcriptional target gene for DJ-1. Reduced expression of LDLR mRNA and protein was observed in DJ-1-knockdown cells and DJ-1-knockout mice and this occurred at the transcription level. Reporter gene assays using various deletion and point mutations of the LDLR promoter showed that DJ-1 stimulated promoter activity by binding to the sterol regulatory element (SRE) with sterol regulatory element binding protein (SREBP) and that stimulating activity of DJ-1 toward LDLR promoter activity was enhanced by oxidation of DJ-1. Chromatin immunoprecipitation, gel-mobility shift and co-immunoprecipitation assays showed that DJ-1 made a complex with SREBP on the SRE. Furthermore, it was found that serum LDL cholesterol level was increased in DJ-1-knockout male, but not female, mice and that the increased serum LDL cholesterol level in DJ-1-knockout male mice was cancelled by administration with estrogen, suggesting that estrogen compensates the increased level of serum LDL cholesterol in DJ-1-knockout female mice. This is the first report that DJ-1 participates in metabolism of fatty acid synthesis through transcriptional regulation of the LDLR gene

Antibody response to sand fly saliva is a marker of transmission intensity but not disease progression in dogs naturally infected with Leishmania infantum

BACKGROUND: Antibody responses to sand fly saliva have been suggested to be a useful marker of exposure to sand fly bites and Leishmania infection and a potential tool to monitor the effectiveness of entomological interventions. Exposure to sand fly bites before infection has also been suggested to modulate the severity of the infection. Here, we test these hypotheses by quantifying the anti-saliva IgG response in a cohort study of dogs exposed to natural infection with Leishmania infantum in Brazil. METHODS: IgG responses to crude salivary antigens of the sand fly Lutzomyia longipalpis were measured by ELISA in longitudinal serum samples from 47 previously unexposed sentinel dogs and 11 initially uninfected resident dogs for up to 2 years. Antibody responses were compared to the intensity of transmission, assessed by variation in the incidence of infection between seasons and between dogs. Antibody responses before patent infection were then compared with the severity of infection, assessed using tissue parasite loads and clinical symptoms. RESULTS: Previously unexposed dogs acquired anti-saliva antibody responses within 2 months, and the rate of acquisition increased with the intensity of seasonal transmission. Over the following 2 years, antibody responses varied with seasonal transmission and sand fly numbers, declining rapidly in periods of low transmission. Antibody responses varied greatly between dogs and correlated with the intensity of transmission experienced by individual dogs, measured by the number of days in the field before patent infection. After infection, anti-saliva antibody responses were positively correlated with anti-parasite antibody responses. However, there was no evidence that the degree of exposure to sand fly bites before infection affected the severity of the infection. CONCLUSIONS: Anti-saliva antibody responses are a marker of current transmission intensity in dogs exposed to natural infection with Leishmania infantum, but are not associated with the outcome of infection

Quantifying the effects of temperature on mosquito and parasite traits that determine the transmission potential of human malaria

Malaria transmission is known to be strongly impacted by temperature. The current understanding of how temperature affects mosquito and parasite life history traits derives from a limited number of empirical studies. These studies, some dating back to the early part of last century, are often poorly controlled, have limited replication, explore a narrow range of temperatures, and use a mixture of parasite and mosquito species. Here, we use a single pairing of the Asian mosquito vector, An. stephensi and the human malaria parasite, P. falciparum to conduct a comprehensive evaluation of the thermal performance curves of a range of mosquito and parasite traits relevant to transmission. We show that biting rate, adult mortality rate, parasite development rate, and vector competence are temperature sensitive. Importantly, we find qualitative and quantitative differences to the assumed temperature-dependent relationships. To explore the overall implications of temperature for transmission, we first use a standard model of relative vectorial capacity. This approach suggests a temperature optimum for transmission of 29°C, with minimum and maximum temperatures of 12°C and 38°C, respectively. However, the robustness of the vectorial capacity approach is challenged by the fact that the empirical data violate several of the model's simplifying assumptions. Accordingly, we present an alternative model of relative force of infection that better captures the observed biology of the vector-parasite interaction. This model suggests a temperature optimum for transmission of 26°C, with a minimum and maximum of 17°C and 35°C, respectively. The differences between the models lead to potentially divergent predictions for the potential impacts of current and future climate change on malaria transmission. The study provides a framework for more detailed, system-specific studies that are essential to develop an improved understanding on the effects of temperature on malaria transmission

Reforming Fiscal Institutions in Resource-Rich Arab Economies: Policy Proposals

This paper traces the evolution of fiscal institutions of Resource Rich Arab Economies (RRAEs) over time since their pre-oil days, through the discovery of oil to their build-up of oil exports. It then identifies challenges faced by RRAEs and variations in their severity among the different countries over time. Finally, it articulates specific policy reforms, which, if implemented successfully, could help to overcome these challenges. In some cases, however, these policy proposals may give rise to important trade-offs that will have to be evaluated carefully in individual cases

Sexual Dimorphism in Bidirectional Sr-Mitochondria Crosstalk in Ventricular Cardiomyocytes

Calcium transfer into the mitochondrial matrix during sarcoplasmic reticulum (SR) Ca2+ release is essential to boost energy production in ventricular cardiomyocytes (VCMs) and match increased metabolic demand. Mitochondria from female hearts exhibit lower mito-[Ca2+] and produce less reactive oxygen species (ROS) compared to males, without change in respiration capacity. We hypothesized that in female VCMs, more efficient electron transport chain (ETC) organization into supercomplexes offsets the deficit in mito-Ca2+ accumulation, thereby reducing ROS production and stress-induced intracellular Ca2+ mishandling. Experiments using mitochondria-targeted biosensors confirmed lower mito-ROS and mito-[Ca2+] in female rat VCMs challenged with β-adrenergic agonist isoproterenol compared to males. Biochemical studies revealed decreased mitochondria Ca2+ uniporter expression and increased supercomplex assembly in rat and human female ventricular tissues vs male. Importantly, western blot analysis showed higher expression levels of COX7RP, an estrogen-dependent supercomplex assembly factor in female heart tissues vs males. Furthermore, COX7RP was decreased in hearts from aged and ovariectomized female rats. COX7RP overexpression in male VCMs increased mitochondrial supercomplexes, reduced mito-ROS and spontaneous SR Ca2+ release in response to ISO. Conversely, shRNA-mediated knockdown of COX7RP in female VCMs reduced supercomplexes and increased mito-ROS, promoting intracellular Ca2+ mishandling. Compared to males, mitochondria in female VCMs exhibit higher ETC subunit incorporation into supercomplexes, supporting more efficient electron transport. Such organization coupled to lower levels of mito-[Ca2+] limits mito-ROS under stress conditions and lowers propensity to pro-arrhythmic spontaneous SR Ca2+ release. We conclude that sexual dimorphism in mito-Ca2+ handling and ETC organization may contribute to cardioprotection in healthy premenopausal females