The cooked meat-derived mammary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) elicits estrogenic-like microRNA responses in breast cancer cells.

The cooking of meat results in the generation of heterocyclic amines (HCA), the most abundant of which is 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Data from epidemiological, mechanistic, and animal studies indicate that PhIP could be causally linked to breast cancer incidence. Besides the established DNA damaging and mutagenic activities of PhIP, the chemical is reported to have oestrogenic activity that could contribute to its tissue specific carcinogenicity. In this study we investigated the effect of treatment with PhIP and 17-β-estradiol (E2) on global microRNA (miRNA) expression of the oestrogen responsive MCF-7 human breast adenocarcinoma cell line. PhIP and E2 caused widespread and largely over-lapping effects on miRNA expression, with many of the commonly affected miRNA reported to be regulated by oestrogen and have been implicated in the initiation and progression of breast cancer. The regulatory activity of the miRNAs we show here to be responsive to PhIP treatment, are also predicted to mediate cellular phenotypes that are associated with PhIP exposure. Consequently, this study offers further support to the ability of PhIP to induce widespread effects via activation of oestrogen receptor alpha (ERα). Moreover, this study indicates that deregulation of miRNA by PhIP could potentially be an important non-DNA-damaging carcinogenic mechanism in breast cancer. © 2014

Hepatic microRNA profiles offer predictive and mechanistic insights after exposure to genotoxic and epigenetic hepatocarcinogens.

In recent years, accumulating evidence supports the importance of microRNAs in liver physiology and disease; however, few studies have examined the involvement of these noncoding genes in chemical hepatocarcinogenesis. Here, we examined the liver microRNA profile of male Fischer rats exposed through their diet to genotoxic (2-acetylaminofluorene) and epigenetic (phenobarbital, diethylhexylphthalate, methapyrilene HCL, monuron, and chlorendic acid) chemical hepatocarcinogens, as well as to non-hepatocarcinogenic treatments (benzophenone, and diethylthiourea) for 3 months. The effects of these treatments on liver pathology, plasma clinical parameters, and liver mRNAs were also determined. All hepatocarcinogens affected the expression of liver mRNAs, while the hepatic microRNA profiles were associated with the mode of action of the chemical treatments and corresponded to chemical carcinogenicity. The three nuclear receptor-activating chemicals (phenobarbital, benzophenone, and diethylhexylphthalate) were characterized by the highly correlated induction of the miR-200a/200b/429, which is involved in protecting the epithelial status of cells and of the miR-96/182 clusters. The four non-nuclear receptor-activating hepatocarcinogens were characterized by the early, persistent induction of miR-34, which was associated with DNA damage and oxidative stress in vivo and in vitro. Repression of this microRNA in a hepatoma cell line led to increased cell growth; thus, miR-34a could act to block abnormal cell proliferation in cells exposed to DNA damage or oxidative stress. This study supports the proposal that hepatic microRNA profiles could assist in the earlier evaluation and identification of hepatocarcinogens, especially those acting by epigenetic mechanisms. © The Author 2012. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved

Time and dose-dependent effects of phenobarbital on the rat liver miRNAome.

In a previous study we had shown that treatment of male Fischer rats with exogenous chemicals for three months resulted in prominent, mode-of-action dependent effects on liver microRNA (miRNA) (Koufaris et al., 2012). Here we investigated how the effects of chemicals on liver miRNA in male Fischer rats relate to the length and dose of exposure to phenobarbital (PB), a drug with multiple established hepatic effects. Importantly, although acute PB treatment (1-7 days) had significant effects on liver mRNA and the expected effects on the liver phenotype (transient hyperplasia, hepatomegaly, cytochrome P450 induction), limited effects on liver miRNA were observed. However, at 14 days of PB treatment clear dose-dependent effects on miRNA were observed. The main effect of PB treatment from days 1 to 90 on liver miRNA was found to be the persistent, progressive, and highly correlated induction of the miR-200a/200b/429 and miR-96/182 clusters, occurring after the termination of the xenobiotic-induced transient hyperplasia. Moreover, in agreement with their reported functions in the literature we found associations between perturbations of miR-29b and miR-200a/200b by PB with global DNA methylation and zeb1/zeb2 proteins respectively. Our data suggest that miRNA are unlikely to play an important role in the acute responses of the adult rodent liver to PB treatment. However, the miRNA responses to longer PB exposures suggest a potential role for maintaining liver homeostasis in response to sub-chronic and chronic xenobiotic-induced perturbations. Similar studies for more chemicals are needed to clarify whether the temporal and dose pattern of miRNA-toxicant interaction identified here for PB are widely applicable to other xenobiotics. © 2013 Elsevier Ireland Ltd

It’s Cool! Analysis of Factors That Influence Smart Thermostat Adoption Intention

Smart thermostats represent an innovative smart home technology and a growing commercial opportunity, yet little is known about the salient factors that affect the adoption of such devices. To address this gap in research, we conduct a three-stage study that progresses through belief elicitation, exploratory factor analysis and confirmatory factory analysis within a nomological network. We leverage the mixed methods approach to explore the factorial structure of salient perceived benefits and concerns associated with smart thermostats, and we examine the effects of the emergent factors on the adoption intention. We discover that a novel factor, which we term techno-coolness, is the key predictor of the smart thermostat adoption intention. Techno-coolness encompasses the perceptions that a smart thermostat can make a home look modern and futuristic, be fun to use, and make the user feel technologically advanced. We also find that compatibility concerns as well as privacy concerns are significant impediments to the smart thermostat adoption intention

The Crowd on the Assembly Line: Designing Tasks for a Better Crowdsourcing Experience

Leveraging crowd potentials through low paid crowdsourcing micro-tasks has attracted great attention in the last decade as it proves to be a powerful new paradigm to get large amounts of work done quickly. A main challenge for crowdsourcers has been to design tasks that trigger optimum outputs from the crowd while providing crowdsourcees with an experience that would attract them to the platform in the future. Drawing mainly from expectancy theory and the motivation through design of work model, we develop and test a theoretical framework to explore the impact of extrinsic reward valence and perceived task characteristics on perceived output measures in crowdsourcing contexts. We specifically focus on the impact of three crowdsourcing task dimensions: autonomy, skill use, and meaningfulness. Our findings provide support for our model and suggest ways to improve task design, use extrinsic rewards, and provide an enhanced crowdsourcing experience for participants

Working on Low-Paid Micro-Task Crowdsourcing Platforms: An Existence, Relatedness and Growth View

Low-paid micro-task crowdsourcing sites present a new workplace that has been increasingly popular. Given recently reported crowd demographics and relevant literature we believe that the understanding of higher-level motivations for workers on these sites is still an under-explored area. Using a qualitative research methodology, we explore workers’ motivations in their natural settings. We conduct interviews with Amazon Mechanical Turk workers and analyze the data through the lens of Alderfer’s existence, relatedness, and growth theory. Our paper contributes new insights to the crowdsourcing literature, specifically that low-paid micro-task crowdsourcing workers aim to satisfy relatedness (connectedness and societal impact), existence (income, basic rights and rewarding experience), and growth needs (impact on self and skill development). We also discuss three additional categories that emerge from our data: sense of control and power, having fun and passing the time. Our findings provide new contributions that are of high relevance to both theory and practice

Using liver miRNA profiles to predict chemical hepatocarcinogenesis

Industrial, agricultural, and pharmaceutical requirements drive the development of a plethora of new chemical entities each year, many of which - for example drugs, pesticides, and food additives - have to be assessed for potential human health hazard. The current benchmark for risk assessement is the lifetime rodent bioassay which is expensive, time-consuming, laborious, requires the sacrifice of numerous animals, and is often irrelevant to humans. Hence alternative strategies to the rodent lifetime bioassay for prediction of chemical carcinogens are being pursued, especially for the liver which is an organ frequently affected by exogenous chemicals due to its detoxifying and metabolic roles. Numerous studies in recent years support the important role of microRNAs in cancer development, including hepatocellular carcinoma. The principal hypothesis of this project was that hepatic microRNA signatures can contribute to the earlier prediction of chemical hepatocarcinogens. Examination of livers from male Fischer rats treated with six chemical hepatocarcinogens, with diverse mode of actions for 90 days revealed that all the tested hepatocarcinogens affected the liver miRNAome from that early stage. Interestingly, a small set of microRNAs were identified whose expression was frequently deregulated by the hepatocarcinogens. Bioinformatic analysis indicates that these microRNAs can regulate pathways which are important in hepatocellular carcinoma. A more detailed investigation of one of those hepatocarcinogens, phenobarbital, showed that its effects on liver microRNAs were both dose and time dependent, with a progressive induction of specific microRNA clusters.Thus this study was the first to investigate in depth the effects of chemical hepatocarcinogens on the liver miRNAome and supports the potential usefulness of hepatic microRNA signatures in risk assessment

Perceived Intelligence and Perceived Anthropomorphism of Personal Intelligent Agents: Scale Development and Validation

Personal intelligent agents are systems that are autonomous, aware of their environment, continuously learning and adapting to change, able to interact using natural language and capable of completing tasks within a favorable timeframe in a proactive manner. Examples include Siri and Alexa. Several unique characteristics distinguish these agents from other traditional information systems. Of particular interest in this work are characteristics of intelligence and anthropomorphism. This paper describes the process of developing two new measures with satisfactory psychometric properties that can be adapted by researchers to assess the users’ perceptions of intelligence and anthropomorphism of PIAs. The measures are validated using data collected from 232 experienced PIA users

THE ROLE OF SAAS SERVICE QUALITY FOR CONTINUED SAAS USE: EMPIRICAL INSIGHTS FROM SAAS USING FIRMS

Despite its success in the software industry, Software-as-a-Service (SaaS) still struggles with fulfilling customer expectations regarding service quality. To contain customer churn rates to low levels, SaaS providers have to address their service quality weak spots and find out which factors are crucial for continued SaaS usage. Drawing on previous service quality literature, we develop a Zone-of-Tolerance (ZOT)-based SaaS-QUAL scale and validate it in a model of IS continuance based on two empirical surveys of SaaS using firms. By doing this, we examine the importance of SaaS service quality factors for shaping customer satisfaction and SaaS continuance intentions. Furthermore, we provide insights into what service factors effectively meet or miss SaaS customer expectations. As a practical contribution, we develop and apply a SaaS-QUAL scale that can be used as a diagnostic tool by SaaS providers and users alike. For researchers, we enrich existing research models on IS continuance by integrating a more fine-grained conceptualization of service quality confirmation that provides stronger explanatory power than in previous models

Customer Retention and Unplanned Purchases on the Web

With the explosion of business to consumer commerce on the web, many companies are faced with new challenges in their efforts to retain customers and increase sales. Our study explores some of the important factors that increase customer intention to return and the number of unplanned purchases made. We find that both the level of perceived control and the shopping enjoyment experienced by new web customers can increase their intention to return. However, repeat customers do not seem to be influenced by either perceived control or shopping enjoyment in terms of their intention to return. We also find that an engaging web store design that utilizes value-added search mechanisms and presents a positively challenging experience can increase the customers' perceived control and enjoyment. Our results also indicate that product involvement is less important to new customers as opposed to repeat customers but the more often customers return to a web store the more their shopping enjoyment is determined by their product involvement. Finally, our study shows that neither perceived control nor shopping enjoyment have any significant impact on the number of unplanned purchases made by customers. Our results deepen our understanding of the consumer online shopping experience and provide guidelines for the more effective design and implementation of web-based stores.Information Systems Working Papers Serie