Total syntheses of the regenerative natural products vinaxanthone, xanthofulvin, and eupalinilide E.

textThe fungal metabolites vinaxanthone and xanthofulvin possess the remarkable ability to restore motor function in animal models of complete spinal cord transection making them the most promising small molecules for the development of spinal cord injury (SCI) therapeutics. A concise nine-step total synthesis of vinaxanthone was accomplished utilizing a biomimetic dimerization of the putative precursor 5,6-dehydropolivione and the first reported synthesis of xanthofulvin was achieved in 15-steps highlighted by an unprecedented enaminone O-to-C carboxyl transfer to forge key carbon-carbon bonds. Both natural products were also identified as positive allosteric modulators of the G-protein coupled receptor (GPCR), GPR91, thus elucidating their modes of action accounting for their regenerative capabilities. Furthermore, a unique ynone coupling reaction was developed in order to access various vinaxanthone analogs for structure activity relationship (SAR) studies. This resulted in the preparation of a small molecule library of 25 vinaxanthone analogs that demonstrated pronounced neuronal regeneration within laser axotomy assays performed in vivo on C. elegans. The plant derived natural product eupalinilide E has been found to promote the ex vivo expansion of hematopoietic stem and progenitor cells (HSPCs) which have the potential to improve the success of medical procedures such as bone marrow transplants. In light of its promising applications, unknown mechanism of action, and scarcity in nature the total synthesis of eupalinilide E was undertaken. Efforts culminated in the first enantioselective total synthesis of the natural product in 20-steps, which showcases a Favorskii rearrangement, borylative enyne cyclization, aldehyde-ene ring closure, and a dual allylic oxidation.Chemistr

Synthesizing Qualitative Evidence: A Roadmap for Information Systems Research

Qualitative synthesis research is an approach that consolidates the output of different qualitative studies to create new subject knowledge. Such work can help reveal more powerful explanations than that seen in a single study, thereby generating increased levels of understanding of a given phenomenon and greater research finding generalizability. Based on a review of the literature and a survey of qualitative researchers, we found that the information systems (IS) domain lacks a clear understanding of qualitative synthesis methods and, as a result, has largely failed to take advantage of this powerful, high-potential methodological opportunity. To address this shortcoming, this paper is the first to provide a rigorous overview of the full suite of 35 qualitative synthesis methods, as well as guidelines that include a three-tiered selection framework. By using the guidelines and framework in tandem, IS researchers are able to select the qualitative synthesis method most appropriate for a given research study, particularly when the research objective involves knowledge integration/aggregation, interpretation/theory development, and/or informing IS practice

Reviewing the Past for a Better Future: Reevaluating the IT Project Retrospective

This paper provides a commentary on previous research to inform our understanding of IT project retrospectives. The literature surrounding project retrospective outcomes, measurement and processes are discussed, and critical factors necessary for project retrospective success are considered. Consequently, semi-structured interviews are undertaken with experienced project managers to determine levels of agreement between research and practitioner disciplines. Outcome findings include multiple project retrospective definitions being used, differing project retrospective outcomes being desired, thirteen project retrospective processes being advocated, and no project retrospective measurements given to confirm whether these outcomes have been successfully achieved. Subsequently, project retrospective processes are presented such that each process has the capability to deliver on any outcome irrespective of its nature. Further research is suggested necessary to pursue a more rigorous and relevant conceptual understanding of the IT project retrospective construct

The Delphi Method Research Strategy in Studies of Information Systems

In this paper, we discuss the nature and use of the Delphi methodology in information systems research. More specifically, we explore how and why it may be used. We discuss criteria for evaluating Delphi research and define characteristics useful for categorizing the studies. We review Delphi application use in IS research over the last 23 years, summarize lessons learned from prior studies, offer suggestions for improvement, and present guidelines for employing this distinctly useful qualitative method in future information systems research studies

Planning for Failure: An Exploratory Study of a Proactive IS Project Recovery Team

Despite extensive research on project management over the past several decades, numerous cases of IS project failure continue to surface, undermining organizational performance in almost every industry. The ongoing nature of this issue obliges the IS discipline to consider alternative approaches to avoiding failure before it’s too late. In this paper, a proactive approach to project recovery is presented – one that involves a full-time recovery team responsible for turning around IS projects in distress. Using the findings gleaned from an in-depth case study inquiry, this paper analyzes the composition and structure of a dedicated project recovery team in a global organization. The investigation revealed (1) a process model of IS project recovery that comprises seven stages of evolution, (2) requisite attributes and skills of project recovery specialists, and (3) the differences between project recovery and project management. The implications arising from this novel study for both research and practice are discussed

Canonical signaling by TGF family members in mesenchymal stromal cells is dispensable for hematopoietic niche maintenance under basal and stress conditions

Mesenchymal stromal cells are an important component of the bone marrow hematopoietic niche. Prior studies showed that signaling from members of the transforming growth factor (TGF) superfamily in mesenchymal stromal cells is required for normal niche development. Here, we assessed the impact of TGF family signaling on niche maintenance and stress responses by deleting Smad4 in mesenchymal stromal cells at birth, thereby abrogating canonical TGF signaling. No alteration in the number or spatial organization of CXCL12-abundant reticular (CAR) cells, osteoblasts, or adipocytes was observed in Osx-Cre, Smad4fl/fl mice, and expression of key niche factors was normal. Basal hematopoiesis and stress erythropoiesis responses to acute hemolytic anemia were normal. TGF-β potently inhibits stromal CXCL12 expression in vitro; however, G-CSF induced decreases in bone marrow CXCL12 expression and subsequent hematopoietic stem/progenitor cell mobilization were normal in Osx-Cre, Tgfbr2fl/fl mice, in which all TGF-β signaling in mesenchymal stromal is lost. Finally, although a prior study showed that TGF-β enhances recovery from myeloablative therapy, hematopoietic recovery following single or multiple doses of 5-flurauracil were normal in Osx-Cre, Tgfbr2fl/fl mice. Collectively, these data suggest that TGF family member signaling in mesenchymal stromal cells is dispensable for hematopoietic niche maintenance under basal and stress conditions

Smart customization : making evidence-based environmental decisions

Thesis (Ph. D.)--Massachusetts Institute of Technology, School of Architecture and Planning, Program in Media Arts and Sciences, 2012.Cataloged from PDF version of thesis.Includes bibliographical references (p. 177-179).This thesis examines the environmental benefits created by the manufacture, distribution, and consumer use of products that are mass customized (MC) or produced "on-demand" and tailored to individual end-user preferences. Traditional mass production (MP) models take advantage of economies of scale by efficiently producing multiple copies of the same standard product. However, this also creates waste throughout the product life cycle. The waste of stocks, transportation, overproduction, and non-actuality (markdowns and disposal due to inability to move products in time) pose a problem for manufacturers to achieve financial and environmental sustainability. Studies have found that the textile industry can lose approximately one-third of total revenue ($300B) a year due to waste alone. The men's dress shirt industry serves as a comparative case study in this research, demonstrating the trade-offs between MC and MP methods and enabling evidence-based environmental decisions by manufacturers and consumers. In addition to an examination of the carbon footprint created by the manufacture and distribution of MC vs. MP men's dress shirts, this study includes experiments to understand, in detail, the environmental consequences of shirt acquisition and consumer use. Experiment participants are provided coupons to "purchase" two new dress shirts (one MC, one MP), which are embedded with washable and dry-clean proof RFID tags. A RFID tracking system deployed at the entrance and exit of the participants' offices collects data over a period of 60 working days to determine overall utilization patterns. Armed with this "post-transaction" information gathered by this tracking methodology and ethnographic findings (information that manufacturers often lack), this thesis provides an evidence-based guide that takes into account the environmental benefits of both MC and MP models to enable manufacturers to produce more sustainable products and consumers to practice "Responsible Consumerism."by Ryan C. C. Chin.Ph.D

Product grammar : construction and exploring solution spaces

Thesis (S.M.)--Massachusetts Institute of Technology, School of Architecture and Planning, Program in Media Arts and Sciences, 2004.Page 79 blank.Includes bibliographical references (p. 77-78).Developing a design methodology that accounts for system- and component-level parameters in the design of products is a challenge for design and manufacturing organizations. Designed products like automobiles, personal electronics, mass-customized homes, and apparel follow design processes that have evolved over time into compartmentalized approaches toward design synthesis. Many products are designed "by committee" because the nature of the problem is sufficiently sophisticated that isolating the different disciplines of engineering, design, manufacturing, and marketing has become the only way to produce a product. This thesis rethinks design methods by critically analyzing design rules and their role in product development. Systematic and unbiased mapping of possible configurations is a method employed in generative design systems. A mapping of a solution space is achieved by parameterizing the constraints of the problem in order to develop a feasible envelope of possibilities at the component and system level. Once parametric modeling begins, then a flexible hierarchical and associative assembly must be put in place to integrate components into the product structure. What results is a complex tree structure of the possible solutions that can be optimized to ergonomic, structural, aerodynamic, manufacturing and material perspectives. The tree structure is organized so that any changes in the component structure can be accommodated at any level. Subsystems can then be easily substituted in order to fit to mass-customization preferences.by Ryan C.C. Chin.S.M