Abstract-In this article we have investigated the mechanisms by which retrograde trafficking regulates the surface expression of the voltage-gated potassium channel, Kv1.5. Overexpression of p50/dynamitin, known to disrupt the dynein-dynactin complex responsible for carrying vesicle cargo, substantially increased outward K ϩ currents in HEK293 cells stably expressing Kv1.5 (0.57Ϯ0.07 nA/pF, nϭ12; to 1.18Ϯ0.2 nA/pF, nϭ12, PϽ0.01), as did treatment of the cells with a dynamin inhibitory peptide, which blocks endocytosis. Nocodazole pretreatment, which depolymerizes the microtubule cytoskeleton along which dynein tracks, also doubled Kv1.5 currents in HEK cells and sustained K ϩ currents in isolated rat atrial myocytes. These increased currents were blocked by 1 mmol/L 4-aminopyridine, and the specific Kv1.5 antagonist, DMM (100 nM). Confocal imaging of both HEK cells and myocytes, as well as experiments testing the sensitivity of the channel in living cells to external Proteinase K, showed that this increase of K ϩ current density was caused by a redistribution of channels toward the plasma membrane. Coimmunoprecipitation experiments demonstrated a direct interaction between Kv1.5 and the dynein motor complex in both heterologous cells and rat cardiac myocytes, supporting the role of this complex in Kv1.5 trafficking, which required an intact SH3-binding domain in the Kv1.5 N terminus to occur. These experiments highlight a pathway for Kv1.5 internalization from the cell surface involving early endosomes, followed by later trafficking by the dynein motor along microtubules. This work has significant implications for understanding the way Kv channel surface expression is regulated. (Circ Res. 2005;97:363-371.)Key Words: atrial myocyte Ⅲ cardiomyocytes Ⅲ intracellular protein transport Ⅲ ion channels Ⅲ potassium channels V oltage-gated K ϩ channels (Kv channels) are intimately involved in the cellular regulation of excitation in all cardiovascular cells, and their activity depends on the presence of active channel subunits at the plasmalemma. Surface expression is regulated by changes in gene expression, 1-3 interactions with accessory subunits, by phosphorylation, and by cellular components that regulate their trafficking to the cell surface. Trafficking can also provide an explanation for the mechanisms by which drugs may act to achieve their therapeutic actions. 4 Although several groups have investigated motifs within K ϩ channels that affect trafficking, [5][6][7][8] little is known about the molecules and machinery involved in these processes in the heart. Surface expression requires movement from the endoplasmic reticulum through the Golgi apparatus to the plasma membrane, and several studies have investigated channel determinants that affect this trafficking process. Motifs in the C termini and pore domains, 6,7 of Kv channels have been implicated in their differential surface expression presumably through effects on forward trafficking. 5 Functional expression of channels can also be regulated by the rem...

This article discusses the pitfalls and opportunities of AI in marketing through the lenses of knowledge creation and knowledge transfer. First, we discuss the notion of "higher-order learning" that distinguishes AI applications from traditional modeling approaches, and while focusing on recent advances in deep neural networks, we cover its underlying methodologies (multilayer perceptron, convolutional, and recurrent neural networks) and learning paradigms (supervised, unsupervised, and reinforcement learning). Second, we discuss the technological pitfalls and dangers marketing managers need to be aware of when implementing AI in their organizations, including the concepts of badly defined objective functions, unsafe or unrealistic learning environments, biased AI, explainable AI, and controllable AI. Third, AI will have a deep impact on predictive tasks that can be automated and require little explainability, we predict that AI will fall short of its promises in many marketing domains if we do not solve the challenges of tacit knowledge transfer between AI models and marketing organizations.

While important insights about the customer engagement concept have been gleaned in recent literature, little remains known regarding the nature and dynamics characterizing customers' engagement with mobile devices, particularly from a longitudinal perspective. Therefore, the objective of this paper is to examine how customer engagement with mobile technology is related to purchase behaviors over time as a dynamic iterative process. A unique database addressing customers' mobile engagement and purchase behaviors is used for the analysis. The results from a vector autoregressive (VAR) model suggest that customer mobile disengagement, where consumers abandon an app, has a strong negative long-term effect on purchase behaviors. However, purchase behaviors can alleviate the level of disengagement. The study, therefore, provides novel findings pertaining to the dynamic interrelationship between customers' engagement with new digital media and purchase behaviors, and therefore it has important scholarly and managerial implications.

Purpose – We do not yet have a good understanding of how generation Y makes decisions. Since this segment will soon wield greater influence in the market place, the purpose of this paper is to carry out an exploratory analysis and develop a framework on generation Y decision making. Design/methodology/approach – The dual-system approach states that individuals use a heuristic-based process (system 1) and/or an analytic-based process (system 2) to make decisions. Evidence from six focus group discussions with generation Y is integrated with this approach. Findings – Generation Y has an active heuristic-based system 1. However, they tend not to evaluate options on their own, i.e. system 2 is “lazy”. Instead, friends, family and digital media play the role of a “proxy” system 2. Research limitations/implications – A limitation is that the study uses data from a small sample of individuals in one country and uses only one methodological approach. Practical implications – Digital media is a vital component of the analytical “proxy” system 2. Therefore, reallocating advertising efforts from traditional media to digital media is perhaps one reason for declining differentiation between brands. Brands that compete on tangible attributes should target individuals designated as “product experts” by their friends. Originality/value – The study identifies different factors and the role they play in influencing generation Y's decisions. The paper has important implications for academics and marketers interested in understanding how generation Y makes decisions.

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Multiple transformative forces target marketing, many of which derive from new technologies that allow us to sample thinking in real time (i.e., brain imaging), or to look at large aggregations of decisions (i.e., big data). There has been an inclination to refer to the intersection of these technologies with the general topic of marketing as “neuromarketing”. There has not been a serious effort to frame neuromarketing, which is the goal of this paper. Neuromarketing can be compared to neuroeconomics, wherein neuroeconomics is generally focused on how individuals make “choices”, and represent distributions of choices. Neuromarketing, in contrast, focuses on how a distribution of choices can be shifted or “influenced”, which can occur at multiple “scales” of behavior (e.g., individual, group, or market/society). Given influence can affect choice through many cognitive modalities, and not just that of valuation of choice options, a science of influence also implies a need to develop a model of cognitive function integrating attention, memory, and reward/aversion function. The paper concludes with a brief description of three domains of neuromarketing application for studying influence, and their caveats.

Woodhouse-Sakati syndrome consists of alopecia, hypogonadism, diabetes mellitus, mild mental retardation, sensorineural deafness and ECG abnormalities. The proband described here has the above-mentioned features and presented with idiopathic thrombocytopenic purpura not reported before. Phenotypic variability is present in the three affected siblings. The two sisters have hypergonadotropic hypogonadism and the brother has hypogonadotropic hypogonadism. Camptodactyly of fourth and fifth fingers is seen in proband and her brother. We report for the first time three affected siblings of Woodhouse-Sakati syndrome in an Indian family.

This study responds to the need for research on individuals' media multitasking behavior using observational data. Media multitasking can have a profound impact on media processing and effects. However, we have little knowledge on when people are likely to engage in media multitasking and, consequently, when these effects are likely to occur. This study examines how three important situational factors-television genres, dayparts, and social viewing-influence the amount of media multitasking. Granular observational data obtained by directly monitoring and recording media consumption behaviors of a large panel at 10-second intervals are used for the analysis. The study reveals that media multitasking with television is most prevalent when people watch sports or engage in channel surfing and less prevalent with commercials, news, and entertainment. Furthermore, the extent of media multitasking is greater in the morning and afternoon than in the evening, and also greater when individuals watch television alone than in the presence of others. Daypart differences are