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PDF file - 158K, Structure of vitamin E (RRR-a-tocopherol, a-TOH, A) and the vitamin E derivative RRR-a-tocopheryloxyacetic acid (a-TEA, B)

The semisynthetic vitamin E derivative alpha-tocopheryloxyacetic acid (α-TEA) induces tumor cell apoptosis and may offer a simple adjuvant supplement for cancer therapy if its mechanisms can be better understood. Here we report that α-TEA also triggers tumor cell autophagy and that it improves cross-presentation of tumor antigens to the immune system. α-TEA stimulated both apoptosis and autophagy in murine mammary and lung cancer cells and inhibition of caspase-dependent apoptosis enhanced α-TEA–induced autophagy. Cell exposure to α-TEA generated double-membrane–bound vesicles indicative of autophagosomes, which efficiently cross-primed antigen-specific CD8+ T cells. Notably, vaccination with dendritic cells pulsed with α-TEA–generated autophagosomes reduced lung metastases and increased the survival of tumor-bearing mice. Taken together, our findings suggest that both autophagy and apoptosis signaling programs are activated during α-TEA–induced tumor cell killing. We suggest that the ability of α-TEA to stimulate autophagy and enhance cross-priming of CD8+ T cells might be exploited as an adjuvant strategy to improve stimulation of antitumor immune responses. Cancer Res; 72(14); 3535–45. ©2012 AACR.

Mixed-mode chromatography combines features of ion-exchange chromatography and hydrophobic interaction chromatography and is increasingly used in antibody purification. As a replacement for flow-through operations on traditional unmixed resins or as a pH-controlled bind-and-elute step, the use of both interaction modes promises a better removal of product-specific impurities. However, the combination of the functionalities makes industrial process development significantly more complex, in particular the identification of the often small elution window that delivers the desired selectivity. Mechanistic modeling has proven that even difficult separation problems can be solved in a computer-optimized manner once the process dynamics have been modeled. The adsorption models described in the literature are also very complex, which makes model calibration difficult. In this work, we approach this problem with a newly constructed model that describes the adsorber saturation with the help of the surface coverage function of the colloidal particle adsorption model for ion-exchange chromatography. In a case study, a model for a pH-controlled antibody polishing step was created from six experiments. The behavior of fragments, aggregates, and host cell proteins was described with the help of offline analysis. After in silico optimization, a validation experiment confirmed an improved process performance in comparison to the historical process set point. In addition to these good results, the work also shows that the high dynamics of mixed-mode chromatography can produce unexpected results if process parameters deviate too far from tried and tested conditions. This article is protected by copyright. All rights reserved.

A move towards the business model of product-service systems (PSS) holds the promise of changing customer behaviour in a more sustainable direction. While this promise of PSS to play a key role in business sustainability has long been recognised, so far, the realised sustainability benefits remain limited. This article sheds light on the reasons why PSS seem to struggle with delivering on their potential. It develops the argument that sustainable PSS are fraught with paradoxical tensions between their marketability and their potential to achieve substantive sustainability benefits. Applying a paradox lens, the article identifies six paradoxes inherent to sustainable PSS and argues that unlocking their full potential to achieve sustainability benefits requires a proactive approach to respond to these paradoxes.

We welcome the opportunity to engage in a dialogue about our work (Hahn & Knight, 2019). In fact, we had hoped that our quantum approach would inspire scholars to reexamine the assumptions that are...

Research on organizational paradox has been burgeoning in recent decades. While consensus is growing on the definition of organizational paradox as persistent contradictions between interdependent ...

In mid-2020, leaders in the field of organizations and the natural environment convened for a conference call to assess the field as it stands and consider reorientations that might elevate its scholarship and amplify its impact. On the call were: Tobias Hahn (ESADE), President of GRONEN, the Group for Research on Organizations and the Natural Environment1 Jennifer Howard-Grenville (Cambridge Judge Business School, University of Cambridge), Deputy Editor of Academy of Management Journal. Tom Lyon (University of Michigan), President of ARCS, the Alliance for Research on Corporate Sustainability Mike Russo (University of Oregon), Editor-in-Chief of Organization & Environment Judith L. Walls (Institute for Economy and the Environment, University of St.Gallen), Chair of the Organizations and the Natural Environment Division of the Academy of Management1 What follows is a lightly edited transcript of our free-flowing conversation, with references that came up in the discussion added.

This paper presents a method for motion planning of fully actuated autonomous surface vehicles in confined waters. The goal is to generate a dynamically feasible trajectory from a given initial state to a given final state without collisions of the vehicle with obstacles. Both the own vehicle and static obstacles are represented as convex polygons. A sampling-based approach is used, where multiple samples in a state space are connected by third-order polynomials. A method is proposed to compute optimal polynomials that both minimize a cost function and account for input variable constraints. Within the cost function, time is weighted together with the control effort. The obtained objective function is a scalar nonlinear function that is solved using numerical minimization techniques. Embedded in a sampling-based motion planning algorithm, the major motion planning problem is solved by many small optimizations. The result is an optimal trajectory from an initial state to a final state, taking into account dynamics and input variable constraints, and avoiding collisions of the vehicle with static obstacles. A simulation is used to demonstrate that the proposed method is basically applicable.

This paper presents an approach to identify the off-diagonal elements of the added mass matrix of a fully actuated marine vessel based on a set of experiments. The off-diagonal elements of the mass matrix characterize the coupled acceleration response of the vessel and are therefore required for the intended design of a control system. The introduced identification scheme utilizes the equivalence between the mass matrix and the coupled acceleration response. The process is extended by a compensation that attempts to match the coupling. A few acceleration experiments are performed with the vessel, applying different compensations for testing. Based on the tested compensations and the measured acceleration responses, the exact compensation and the mass matrix can be reconstructed finally. The exact compensation is sometimes desired itself, rather than the off-diagonal elements of the mass matrix. It makes the coupled process appear as separate SISO processes, which is convenient for controller design.

Escalating ecological degeneration and mounting social challenges highlight the need to rethink the current way of doing business. Human and business activities rely on functioning social-ecological systems but tend to take these for granted. Extant research on business sustainability has acknowledged the relevance of sustainability concerns for business strategy and organizing. Yet, dominant conceptualizations of business sustainability remain focused on the organization and its business case, in the quest to find strategies that translate less harmful social and environmental practices into competitive advantages. Only few scholars have gone beyond such a commercial logic and adopted a systems approach to derive business strategies from the logic of social-ecological systems. In this article, we propose that taking a systems approach means to conceptualize business sustainability in terms of regenerative business, that is, businesses that enhance, and thrive through, the health of social-ecological systems in a co-evolutionary process. As our main contribution, we develop the restore-preserve-enhance scale for regenerative business strategies reflecting a continuum of strategies for regeneration. These strategies follow from two main principles and related criteria for a systems-based level of aspiration and an adaptive management approach to regeneration. By doing so, we fundamentally shift the focus away from a business logic to a systems logic. Importantly, we offer concrete strategies for organizations to contribute to life-supporting conditions in social-ecological systems.

Statistical arbitrage refers to a suite of quantitative investment strategies employed chiefly by hedge funds and proprietary trading firms. The arbitrageur can draw on a number of different approaches to identify and exploit an arbitrage opportunity, though the literature is broadly segmented by the canonical distance, cointegration and time series perspectives. Since the initial academic investigation of statistical arbitrage, its profitability has continued to diminish thanks largely to the increasing proportion of non-convergent opportunities. This paper surveys the existing literature, with particular emphasis given to evidence of statistical arbitrage failure, before unifying the distance, cointegration and time series perspectives under a single explicit model. The failure of statistical arbitrage opportunities is shown to be the direct consequence of implicit model assumptions that are inconsistent with the empirical literature. An alternative model is proposed, and evidence of its relative performance discussed.

Ethics are becoming a component of best practices in ocean science and observing systems, with the research community facing a duty to society to maximize the efficient use and benefits that stem from investments in ocean science/monitoring. Sustained ocean observing systems on issues of global importance are coordinated, internationally sanctioned and making the most out of the resources accorded to them and consequently fulfilling their duty to society. However, globally huge investments are made annually in establishing infrastructure for shorter-term, punctual studies that address targeted as opposed to broad science needs. More could be done to maximize the benefits and impacts of these punctual efforts. Given punctual infrastructure’s small and frequently transient nature, connections to enable sharing will probably be done locally, and both potential additional users and owners of the infrastructure will need to be energetic, receptive and flexible. The accommodation of new uses will have to be balanced against any costs of these additional activities, which could pose an ethical dilemma in themselves if they compromise the infrastructure’s ability to meet its original intent. However, such adaptive infrastructures may be the most efficient way to provide the resources needed to identify and monitor emerging or new ocean stressors.

Organizational paradoxes must first be recognized by managers before they can respond to them. Yet scholars have adopted different perspectives on how paradoxical tensions become salient and engender management responses. Some approaches have focused on the socially constituted nature of paradoxes, and others on the inherent aspects of paradoxes in the environment. The authors propose an approach that gives ontological meaning to both the socially constituted and inherent nature of organizational paradoxes. Our approach, which is inspired by quantum physics, opens up new opportunities for engaging with the socio-materiality of paradoxes, how they are measured, and the implications this has on the probabilities of managing organizational responses to paradox.

We survey the works applying text analytics to the study of news media in financial markets beyond intraday horizons, and expand into the fundamental economic theory and concepts relevant to the field. We compare and contrast the news sources, textual analysis methods and empirical modelling approaches adopted within the literature. We distil and categorise the key empirical insights, and summarise the bibliographic history of the literature so far. While this rapidly growing field has yielded many exciting discoveries, there are a number of promising avenues for future research which will only benefit from continued advances in computational technology.

For mechanistic modeling of ion exchange (IEX) processes, a profound understanding of the adsorption mechanism is important. While the description of protein adsorption in IEX processes has been dominated by stoichiometric models like the steric mass action (SMA) model, discrepancies between experimental data and model results suggest that the conceptually simple stoichiometric description of protein adsorption provides not always an accurate representation of nonlinear adsorption behavior. In this work an alternative colloidal particle adsorption (CPA) model is introduced. Based on the colloidal nature of proteins, the CPA model provides a non-stoichiometric description of electrostatic interactions within IEX columns. Steric hindrance at the adsorber surface is considered by hard-body interactions between proteins using the scaled-particle theory. The model's capability of describing nonlinear protein adsorption is demonstrated by simulating adsorption isotherms of a monoclonal antibody (mAb) over a wide range of ionic strength and pH. A comparison of the CPA model with the SMA model shows comparable model results in the linear adsorption range, but significant differences in the nonlinear adsorption range due to the different mechanistic interpretation of steric hindrance in both models. The results suggest that nonlinear adsorption effects can be overestimated by the stoichiometric formalism of the SMA model and are generally better reproduced by the CPA model.

Business sustainability urges firms to simultaneously address economic, ecological, and social concerns. It innately combines different potentially competing organizational elements. Therefore, sustainability represents a suitable context for the study and practice of hybridity. Based on an understanding of hybridity as a continuum, in this chapter, the author distinguish between four different forms of hybridity for business sustainability, depending on the degree of integration and autonomy of sustainability initiatives in business organizations. With ceremonial hybridity, businesses only leave the impression to pursue business and sustainability goals but focus their practices on conventional business priorities. Contingent hybridity denotes an approach where ecological and social concerns are only pursued to the extent that they align with business goals. With peripheral hybridity, firms pursue sustainability initiatives in their own right but do not integrate them with core business activities. Full hybridity puts both business as well as sustainability at the core of the organization without emphasizing one over the other. These different forms of hybridity in business sustainability are illustrated with examples from various business organizations. By characterizing different degrees of hybridity in business sustainability, the argument and the examples highlight how organizational hybridity and business sustainability can fruitfully inform one another. The author develop research opportunities for using business sustainability as a context for studying different degrees as well as the dynamics of hybrid organizing and for using different degrees of hybridity for achieving a better understanding of different pathways toward substantive business contributions to sustainable development.