Eph/Ephrin-Based Protein Complexes: The Importance of cis Interactions in Guiding Cellular Processes

Although intracellular signal transduction is generally represented as a linear process that transmits stimuli from the exterior of a cell to the interior via a transmembrane receptor, interactions with additional membrane-associated proteins are often critical to its success. These molecules play a pivotal role in mediating signaling via the formation of complexes in cis (within the same membrane) with primary effectors, particularly in the context of tumorigenesis. Such secondary effectors may act to promote successful signaling by mediating receptor-ligand binding, recruitment of molecular partners for the formation of multiprotein complexes, or differential signaling outcomes. One signaling family whose contact-mediated activity is frequently modulated by lateral interactions at the cell surface is Eph/ephrin (EphA and EphB receptor tyrosine kinases and their ligands ephrin-As and ephrin-Bs). Through heterotypic interactions in cis, these molecules can promote a diverse range of cellular activities, including some that are mutually exclusive (cell proliferation and cell differentiation, or adhesion and migration). Due to their broad expression in most tissues and their promiscuous binding within and across classes, the cellular response to Eph:ephrin interaction is highly variable between cell types and is dependent on the cellular context in which binding occurs. In this review, we will discuss interactions between molecules in cis at the cell membrane, with emphasis on their role in modulating Eph/ephrin signaling.

Towards responsible science and technology: How nanotechnology research and development is shaping risk governance practices in Australia

Incorporating perspectives of multiple stakeholders concerning the appropriate balance of risks and benefits of new and potentially disruptive technologies is thought to be a way of enhancing the societal relevance and positive impacts of those technologies. A risk governance approach can be instrumental in achieving balance among diverse stakeholders, as it enables decision-making processes informed by multiple dimensions of risk. This paper applies a risk governance approach to retrospectively examine the development of nanotechnology research and development (R&D) in Australia to identify how risk governance is reflected in the practices of a range of stakeholders. We identify ten risk-related challenges specific to nanotechnology R&D based on a review of the international literature, which provided the foundation for documenting how those working in the Australian nanotechnology sector responded to these global risk-related challenges. This case study research draws on a range of sources including literature review, semi-structured interviews, and a combination of qualitative and quantitative approaches for data analysis to identify key themes and generate visualisations of the interconnections that exist between risk governance practices. The ability to visualise these interconnections from the qualitative data is a key contribution of this research. Our findings show how the qualitative insights and professional experiences of nanotechnologists provide evidence of how risk governance approaches have been operationalised in the Australian nanotechnology R&D sector. The findings generate three important insights. First, the risk research undertaken by Australian nanotechnologists is interdisciplinary and involves multiple stakeholders from various disciplines and sectors. Unlike traditional risk governance approaches, our findings document efforts to assess, not only physical risks, but also social and ethical risks. Second, nanotechnology risk governance is a non-linear process and practices undertaken to address specific challenges occurred concurrently with and contributed to addressing other challenges. Third, our findings indicate that applying a risk governance approach enables greater intersection and collaboration, potentially bridging any disconnect between scientists, policymakers, and the public to realise transdisciplinary outcomes. This research highlights opportunities for developing systematic methodologies to enable more robust risk governance of other new and emerging technologies.

Extraction of transforming sequences and sentence histories from writing process data: a first step towards linguistic modeling of writing

Producing written texts is a non-linear process: in contrast to speech, writers are free to change already written text at any place at any point in time. Linguistic considerations are likely to play an important role, but so far, no linguistic models of the writing process exist. We present an approach for the analysis of writing processes with a focus on linguistic structures based on the novel concepts of transforming sequences, text history, and sentence history. The processing of raw keystroke logging data and the application of natural language processing tools allows for the extraction and filtering of product and process data to be stored in a hierarchical data structure. This structure is used to re-create and visualize the genesis and history for a text and its individual sentences. Focusing on sentences as primary building blocks of written language and full texts, we aim to complement established writing process analyses and, ultimately, to interpret writing timecourse data with respect to linguistic structures. To enable researchers to explore this view, we provide a fully functional implementation of our approach as an open-source software tool and visualizations of the results. We report on a small scale exploratory study in German where we used our tool. The results indicate both the feasibility of the approach and that writers actually revise on a linguistic level. The latter confirms the need for modeling written text production from the perspective of linguistic structures beyond the word level.

Teaching Circular Economy and Lean Management in a Learning Factory

Traditionally, industries followed a linear process of resources consumption: taking raw materials from nature, transforming them into products, and selling them to consumers (who discarded them when they were no longer useful). Nowadays, due to the sustainable development concerns, there is an increasing awareness on the society for reuse, repair, recycling, and remanufacturing to avoid resource depletion and achieve waste reduction. Following this idea, with the aim to train students and practitioners in lean manufacturing and circular economy concepts and tools, a learning process organized in three sequential phases was developed, starting with the manufacture of a toy car (25 kg and over 100 pieces) using a traditional push system, then reengineering the process to implement pull system and lean manufacturing concepts, and finally, considering a circular economy pull system through the reuse and recycling of parts and components. In this way, the importance of reducing waste in manufacturing and the reduction in the use of raw materials by considering the 3Rs is highlighted.

Impact of Intradialytic Fiber Clotting on Dialyzer Extraction and Solute Removal: A Randomized Cross-Over Study

Previous studies revealed the importance of biocompatibility, anticoagulation strategy, and dialysis mode and duration on fiber blocking at the end of a hemodialysis session. The present study was set up in ten hemodialysis patients to relate fiber patency to dialyzer extraction and removal of small and middle molecules. With only 1/4th of the regular anticoagulation dose, and using a Solacea™ 19H and FX800 CorDiax dialyzer, fiber patency was quantified using 3D micro-CT scanning for different dialysis durations (i.e. 60, 120 and 240min). While Solacea™ showed good performance in all test sessions, fiber blocking in the FX800 CorDiax did not follow a linear process during dialysis, but was rather accelerated near the end of dialysis. Dialyzer extraction ratios were correlated with the percentages of open fibers. While the fiber blocking process affected extraction ratios (i.e. for phosphorus and myoglobin in the FX800 CorDiax), it had only minor impact on the removal of toxins up to at least 12kDa.

Empirical investigation of risk management practices

In risk management research, dealing with known risks and helping companies foresee new risks are areas for subject matter experts. In practice, risk management is often perceived as a set of formal tools and procedures that must be delegated to the professionals. Despite this overall perception of risk, general managers, department managers, and other senior or line managers in organizations deal with questions associated with risk on a daily basis. They are, therefore, sometimes—even without consciously realizing it—involved in risk management practices. This article aims to analyze 'managers' involvement in risk management by empirically exploring how managers identify, assess, and respond to risks. Based on thematic analysis of observational and interview data, management practices used to manage risks were identified, and risk management as a non-linear process that is anchored on the strategic and operational levels and supported by learning from failures was defined. Two different ways of risk management can co-exist in an organization as a result of formal Enterprise Risk Management implementation.

Dealing with the Machine: Strategies of Pilots and Doctors Towards Technological Integration

As a global and profuse fact, all professions are more or less affected by the rapid penetration of technology in their domain of practice. As the technological capacity progresses, we observe a gradual replacement of human skills by machine-guided procedures. Although such a gradual passage undeniably reduces the human presence in the practice of a profession, the transfer seems not to be a linear process. It has rather a pivoting character, comprising a series of ambivalences and contradictions. Consequently, professionals tend to keep their already acquired knowledge and ability through education and practice, and instead submissively abandon their place to technological tools. From such a perspective, we discuss in this article the strategies of resistance adopted and developed by professionals for keeping their professional power. Among a variety of professions, we choose to focus on medicine and aviation, due to their two fundamental distinctive characteristics: Both have (1) a high degree of technological determination, and (2) accomplishing vital functions. For this purpose, we discuss the strategies of resistance towards technology by professionals, throughout data we gathered from some field research conducted with doctors and pilots.

Contesting neoliberalism: Mapping the terrain of social conflict

This article explores the terrain of social conflict as it developed across advanced capitalist democracies throughout the ‘age of austerity’ that followed the global economic crisis. It shows how a (broadly defined) working class mobilised in different ways in different capitalist contexts, contesting the institutional forms (and the crises that emerged from them) which constitute each particular model of capitalism. Considered this way, we are able to conceptualise and explain the forms of working-class mobilisation that have emerged in opposition to contemporary neoliberalism. In doing so, we go beyond a narrow focus on workplace-focused or trade-union-led forms of working-class mobilisation, highlighting the continuing contestation of neoliberal capitalism. Drawing on a protest event analysis of 1,167 protest events in five countries (Spain, Germany, Japan, the United States and the United Kingdom), and developing a Régulation Theory approach to the study of protest/social movements, we provide an overview of the most visible patterns of social contestation in each national neoliberal capitalist context, tracing links to the institutional configurations that constitute those national models of capitalism. While there exists no direct (linear) process of causality between the model of neoliberal capitalism and the forms of mobilised dissent witnessed, nevertheless we are able to clearly trace the different pressures of capital accumulation that have given rise to the protest/social movements identified in each case, thereby allowing us to gain a better insight into both each particular model of capitalism and the forms of dissent that constitute it.

It Is Simple, It Is Complicated

History is not a strictly linear process; our progress as society is one full of contradictions. This we have to bear in mind when trying to find answers to pressing challenges related to and even caused by the digital transformation. In this chapter, we reflect on contradictory aspects of Digital Humanism, which is an approach to foster the control and the design of digital infrastructure in accordance with human values and needs. Seemingly simple solutions turn out to be highly complex when looking at them more closely. Focusing on some key aspects as (non-exhaustive) examples of the simple/complicated dilemma, we argue that, in the end, political answers are required.

Designed Parameters: Advancing Parametric Software in the Architectural Design Process

<p>Architects use computers predominantly to digitise a design process that has been in use prior to the advent of the computer. Traditional analogue concepts are transferred into and sculpted through the digital world but the overall process has remained mostly unchanged for decades. Merely digitising a known process does not utilise the full power of the computer and its near limitless ability to compute. For an architect, design of the built environment is highly important especially if they are to optimise the physical, phenomenological and psychological aspects of the space. The process of designing an architectural space is riddled with possibilities or variables that architects have used historically to aid in the design of the built environment, including but not limited to: object relationships, climate, site conditions, history, habitibility and the clients input - all project requirements that must somehow be quantified into a built object. This information is key for an architect as it will inform and form the architecture which is to be designed for the project at hand. This information, however useful, is not easy to integrate into every aspect of the design without intensive planning, problem solving and an exploration of almost an infinite number of possibilities. This is where parametric design can be used to aid in the design. More of the fundamental aspects of the information gathered in a project can be programmed into a computer as parameters or relationships. Once this information has been quantified, the designer can run through iterations of a design which are defined by these parameters. This is not a random process. It is controlled by the designer and the outcome is a product of how the architect designs the parameters, or relationships between components of the design. Parametric design offers a shift from merely digitising design ideas to using programmed constraints derived through the design process to influence and augment the design envisioned by the architect. Parametric design allows the system to be changed holistically and updated through the alteration of individual components that will then impact the form of the design as a whole – creating a non-linear process that is connected throughout all design phases. This thesis seeks to explore parametric design through its implementation within a group design project to decipher how a parametric process grounded in an understanding of contemporary digital fabrication can inform architectural space. To explore parametric design, this thesis will practice this re-envisioned design process through three design phases. The first phase is the foundational knowledge stage where the applications of digital workflow, computer models, tools and material explorations are examined. Second is the production of a prototype to investigate lessons learnt from phase one and apply these lessons to an actual parametric system used to design a prototype. The final stage will be a developed design process that will further explore a parametric system and its architectural applications. These phases will be developed through a series of prototypes in the form of material explorations and scale artefacts which will explore how it would be used to address many of the designs facets from sensual to corporeal.</p>