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Kelz MB Dent GW Therianos S Marciano PG McIntosh TK Coleman PD Eberwine JH 《Science of aging knowledge environment : SAGE KE》2002,2002(1):re1
Neurodegenerative diseases typically affect subpopulations of neurons. Characterizing these vulnerable cells and identifying the factors that make them susceptible to damage while neighboring cells remain resistant are essential to the understanding of molecular pathogenesis that underlies neurodegenerative diseases. Classically, molecular analysis of the central nervous system involves the identification and isolation of an anatomic region of interest; next, the relevant tissue is pulverized, and the resulting homogenate is analyzed. Although this method provides useful data, its effectiveness diminishes when used in areas of high cellular diversity or in instances in which one cell type is lost as a consequence of selective cell death or quiescence. A technique that affords the ability to assess molecular events in a very precise anatomical site would provide a powerful tool for this research discipline. In this review, we discuss the amplification of messenger RNA from single neural cells and the subsequent use of the RNA to probe DNA microarrays in an effort to create cell-specific molecular profiles. Specifically, recent work in single-cell expression profiling in Alzheimer's and Huntington's diseases is discussed. We also review some new work with neural stem cells and their application to restorative neurobiology. Finally, we discuss the use of cell-specific molecular profiles to better understand the basics of neuronal cell biology. 相似文献
83.
This paper studies two‐stage lot‐sizing problems with uncertain demand, where lost sales, backlogging and no backlogging are all considered. To handle the ambiguity in the probability distribution of demand, distributionally robust models are established only based on mean‐covariance information about the distribution. Based on shortest path reformulations of lot‐sizing problems, we prove that robust solutions can be obtained by solving mixed 0‐1 conic quadratic programs (CQPs) with mean‐risk objective functions. An exact parametric optimization method is proposed by further reformulating the mixed 0‐1 CQPs as single‐parameter quadratic shortest path problems. Rather than enumerating all potential values of the parameter, which may be the super‐polynomial in the number of decision variables, we propose a branch‐and‐bound‐based interval search method to find the optimal parameter value. Polynomial time algorithms for parametric subproblems with both uncorrelated and partially correlated demand distributions are proposed. Computational results show that the proposed models greatly reduce the system cost variation at the cost of a relative smaller increase in expected system cost, and the proposed parametric optimization method is much more efficient than the CPLEX solver. 相似文献
84.
The transformation of product-centric businesses towards service provision is claimed to be a viable strategy for manufacturers across industries and sectors. However, previous research on servitization has not paid sufficient attention to explicitly investigating its suitability for manufacturers operating in different organizational environments. Accordingly, the purpose of this study is to establish propositions on the contingency factors in the organizational environment that affect the servitization of manufacturers at the industry level. Drawing on the theory of organisational ecology, the propositions include the effects of population density, competing populations, resource dependency, institutional linkages, technology, and political forces. Our study suggests that the operating environment explains at least part of the difficulties in the servitization process, which have been identified in previous studies, but whose causes have remained without full explanation. The study adds to the current understanding of the contingencies of transformation toward service provision and contributes to the managerial decision-making processes related to servitization. 相似文献
85.
Ying‐Ju Chen J. George Shanthikumar Zuo‐Jun Max Shen 《Production and Operations Management》2015,24(9):1430-1440
This study examines the peer‐to‐Peer interactions among farmers when both knowledge learning and sharing are available. We construct a stylized model in which heterogeneous farmers are endowed with their initial production capabilities and can post questions in the platform for help. A representative expert regularly monitors the forum and provides answers to the farmers’ questions, but may be non‐responsive sometimes due to the limited capacity. A knowledgeable core user (farmer) can choose to be silent or responsive, and is allowed to strategically determine the informativeness of her answers. The farmers face the minimum quantity restriction for attracting the buyers, and must make production before the time of sales. We show that in equilibrium the core user never provides answers that are more informative than the expert's, irrespective of her ex ante knowledge level. Redesigning or restructuring the platform does not help eliminate this inefficient knowledge provision. We also find that hiring more staff to frequently monitor the forum turns out to be detrimental for the peer‐to‐peer interactions. Moreover, the competition on knowledge sharing between the platform expert and the core user features strategic complementarity sometimes but strategic substitution at other times. Third, charging for the platform usage may discourage uninformative answers, but it could also discourage the core user from sharing knowledge with other farmers. 相似文献
86.
Jason Landon Katie Palmer du Preez Maria Bellringer Alyssa Page Max Abbott 《International Gambling Studies》2016,16(1):49-66
In New Zealand, a pop-up message feature that interrupts gambling is mandatory on all electronic gaming machines (EGMs) in all venues. The present research documented the views and experiences of pop-up messages from a range of gamblers and gambling venue staff. A series of focus groups was held with 40 gamblers (ranging from infrequent gamblers to current/former problem gamblers), and 19 staff from casino and non-casino venues. Most participants thought that pop-up messages were ineffective as a harm-minimization measure. Venue staff participants viewed pop-up messages much more negatively than gamblers, who were generally accepting of their existence and sometimes described them as useful. Venue staff participants were also very negative about the additional hassles and confusion they believed to be caused by pop-up messages, and a range of problems they perceived with their accuracy. Nonetheless, there was a consistent although less prevalent view that pop-up messages were useful in reducing gambling harm and potentially bringing harmful gamblers to the attention of others. Participants raised some possibilities for enhancing their effectiveness; these were generally consistent with the evidence base developed since the introduction of pop-up messages in the New Zealand gambling environment. 相似文献
87.
In their seminal review article on board of directors, Johnson, Daily, and Ellstrand (1996) distinguished between the control, service, and resource dependence tasks of the board and called for a stronger focus on board service tasks. Following this call, service tasks of boards have been subject to increased scholarly attention, with new theoretical perspectives and methods introduced. This paper aims at presenting the current state of research on board service tasks, departing from, and building on, the contribution of Johnson and colleagues. In doing so, we employ an Input-Process-Output-Context framework and craft an agenda for how future research could accommodate new governance practices and progress the field. Our review is relevant and timely as studies on the subject are gaining traction both in corporate governance and general management journals. Furthermore, our review on board service tasks proposes new alternative approaches to studying corporate governance which are especially appropriate in times in which a rethink of corporate governance frameworks and concepts is urgently needed. 相似文献
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This article hypothesizes that individuals’ environmental attitudes depend not only on their knowledge, interests, emotions, and values but also on the social context in which they live. We test this hypothesis by analyzing the 2000/01 ISSP‐II Survey on Environmental Attitudes; the data include respondents from 23 countries. Our findings show that individual characteristics influence both “pessimistic environmental orientations” and “the willingness to act in favor of the environment.” As for social context, the level of development and affluence, the degree of political centralization, the presence of green movements and parties, and the degree of objective pollution in a country are all important. However, their influences on fatalism and willingness vary. 相似文献