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"King, Dan"
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Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex
The anticancer agent indisulam inhibits cell proliferation by causing degradation of RBM39, an essential mRNA splicing factor. Indisulam promotes an interaction between RBM39 and the DCAF15 E3 ligase substrate receptor, leading to RBM39 ubiquitination and proteasome-mediated degradation. To delineate the precise mechanism by which indisulam mediates the DCAF15–RBM39 interaction, we solved the DCAF15–DDB1–DDA1–indisulam–RBM39(RRM2) complex structure to a resolution of 2.3 Å. DCAF15 has a distinct topology that embraces the RBM39(RRM2) domain largely via non-polar interactions, and indisulam binds between DCAF15 and RBM39(RRM2), coordinating additional interactions between the two proteins. Studies with RBM39 point mutants and indisulam analogs validated the structural model and defined the RBM39 α-helical degron motif. The degron is found only in RBM23 and RBM39, and only these proteins were detectably downregulated in indisulam-treated HCT116 cells. This work further explains how indisulam induces RBM39 degradation and defines the challenge of harnessing DCAF15 to degrade additional targets.
The crystal and cryo-electron microscopy structure analysis of the DCAF15–DDB1–DDA1–indisulam–RBM39 complex revealed the detailed mechanism of action of indisulam-induced RBM39 degradation and defined an α-helical degron motif in RBM39.
Journal Article
The Sources and Consequences of the Fluent Processing of Numbers
Consumers often like fluently processed stimuli. The authors find that one source of fluency for numerical stimuli is the generation of a number through common addition (e.g., 1 + 1 through 10 + 10) and common multiplication (2 × 2 through 10 × 10) problems (Study 1). Common addition and multiplication problems (arithmetic), or their operands, can be used to prime a number and increase its fluency (Study 3). The benefits of arithmetic and operand primes are limited to single primes (i.e., more primes are not necessarily better) (Study 5). Number fluency is relevant to creating numeric brand names (Study 2), enhancing the liking of numeric brand names through advertising (Study 4), and executing price promotions (Study 6).
Journal Article
Rehabilitation and Repair of Concrete Overlays
Concrete overlays are a growing solution in the United States for pavement rehabilitation and preservation. Many different overlay types and designs can be used based on existing conditions and to achieve a variety of design goals. Recent performance studies have indicated that concrete overlays are capable of providing an extended service life of 35 years or more. However, the intended design life of an overlay may be shorter, and in some cases, overlays experience early distresses and failures. Because many agencies are new to concrete overlays, there is a growing need to identify best practices for rehabilitation and repair of these pavements. This paper presents a survey of typical shortand long-term distresses that have been observed on US concrete overlay projects. Common failure modes vary based on overlay type and design details, and distresses frequently depend on local materials and climate conditions. Best practices and case studies for rehabilitation and repair of concrete overlays are identified, offering options both for extension of concrete overlay service life as well as rehabilitation or reconstruction with a new pavement surface.
Journal Article
The scorecard solution
Simply \"making the numbers\" is no longer enough to remain competitive. In today's high-pressure environment, organizations need to overachieve. That level of success requires a clear and objective view of the business - because even the most courageous leader can't steer a ship in the dark.Is the enterprise Agile? Resilient? Vulnerable? Or Lagging?The Scorecard Solutionprovides the answer. The book introduces a data-centric tool - the Organizational Prowess Scorecard - that precisely measures the capabilities needed for sustainable growth. Analyzing the dimensions of talent, strategy, and execution produces a baseline score, and shines a light on the performance gaps that hold a business back. With the facts in hand, readers then learn how to: Position the organization to meet ambitious goalsBring strategies to life through an execution frameworkDesign a dashboard to track progress and flag problemsFoster a winning culture Organizations that maintain the status quo will be left in the dust.The Scorecard Solutionhelps companies chart a course for rapid change - and outperform the competition every time.
eBook
Commentary: Studying Higher Education Administrators' Orientation to Public Service
Although the role of the college administrator as public servant is an undergirding motivational concept that is reportedly embraced by a number of higher-echelon college and university administrators, Daniel James Palmer points out in his article \"College Administrators as Public Servants\" that it is a complex and sometimes elusive concept. While we do have instruments that are well designed to assess individual commitments toward servant leadership, and while several of those instruments are particularly designed to assess factors that are closely related to public administration, we need to recognize at least two survey design limitations that can substantially affect the outcomes of research in this area. Adapted from the source document.
Journal Article
Author Correction: Structural basis of indisulam-mediated RBM39 recruitment to DCAF15 E3 ligase complex
An amendment to this paper has been published and can be accessed via a link at the top of the paper.An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Journal Article
From physical space to mental space: feelings of being physically constrained increase consumer preference for mind-expanding products
This research examines whether and how feelings of physical constraints can increase consumers’ preference for mind-expanding products, such as products that broaden perspectives and viewpoints. Three studies show that feelings of physical constraints (such as when consumers commute and buckle their seatbelts, which restricts their movement) motivate them to increase mental space and break free from mental limitations as an alternative way to compensate for the physical restrictions they experience. As a result, consumers prefer mind-expanding products more because the content of these products helps them expand their mental space. Together, the current research integrates and extends theories of fluid compensatory consumption and offers actionable managerial implications for marketers.
Journal Article
Felt something, hence it works: Merely adding a sensory signal to a product improves objective measures of product efficacy and product evaluations
Product efficacy is an important driver of product evaluation and product usage. This research examines how marketers can improve perceived and actual product efficacy. Given the managerial ease of adjusting product design, we demonstrate that adding a sensory signal (e.g., tingling, cooling, fizzing) to a product that promises positive outcomes would improve product evaluations and actual product efficacy. In five studies (and two additional studies reported in the Web Appendix), we show that sensory signaling (vs. nonsignaling) products elicit actual product choice and improve product evaluations, repurchase likelihood, recommendation likelihood, as well as objective measures of product efficacy (such as consumer performance). This occurs because the sensory signals make consumers feel a greater transfer of benefits to the body during product usage. We further demonstrate that the effect holds even when persuasion knowledge is activated. Together, this research provides important insights on product designs that benefit not only marketers but also consumers.
Journal Article