Editorial: Insights (June 2018)

Existing solutions for analysis and optimization of manufacturing processes, such as online analysis processing or statistical calculations, have shortcomings that limit continuous process improvements. In particular, they lack means of storing and integrating the results of analysis. This makes the valuable information that can be used for process optimizations used only once and then disposed. The goal of the Advanced Manufacturing Analytics (AdMA) research project is to design an integrated platform for data-driven analysis and optimization of manufacturing processes using analytical techniques, especially data mining, in order to carry out continuous improvement of production. The achievement of this goal is based on the integration of the data related to the manufacturing processes, especially from Manufacturing Execution Systems (MES), with the other operating data, e.g. from Enterprise Resource Planning (ERP) systems. This work is based on AdMA platform described in [1] and Deep Business Process Optimization platform described in [2]. It is focused on the conceptual development of the Process Insight Repository, which is a part of the AdMA platform. The Process Insight Repository is aimed at storing the manufacturing process related data and the insights associated with it. Being part of the AdMA platform, the Process Insight Repository is oriented on storing the insights retrieved by application of data mining techniques to the data of manufacturing processes, so that the newly extracted knowledge can be stored along with the process data itself. Chapter 2 describes the conceptual schema of the Process Insight Repository. The conceptual schema defines what data must be stored in the Process Insight Repository and how different parts of this data are interconnected. Chapter 3 provides a review of technologies that can be used for the implementation of the Process Insight Repository. This includes technologies for storing manufacturing process data, free form knowledge and data mining related data. Chapter 4 describes the details of the prototype implementation of the Process Insight Repository. The result of this work is the created conceptual schema of the Process Insight Repository and a prototype implementation as a proof of concept.

Towards improving detection of early warning signals within organizations : an approach to the identification and utilization of underlying factors from an organizational perspective

Practitioners of dreamwork have long understood that exploring dreams has the potential to be a source of insight, but empirical research evidencing this has generally been lacking, especially in non-clinical settings. Additionally, many of the factors that influence dreamwork efficacy remain to be discovered. The present study aimed to provide evidence for the insight-generating potential of dreamwork, and to investigate a potential factor that may influence how effective a dreamwork session is: the level of experience of the dreamer. Participants (29 (15 experienced and 14 inexperienced in dreamwork)) took part in two discussions: a dream discussion and a waking-life event discussion, using the Schredl “Listening to the Dreamer” method of dreamwork and an adapted version of this for discussing waking-life events. Results indicated that dreamwork led to significantly higher levels of Exploration-Insight and Continuity Insight in comparison to a waking-life event discussion. Levels of Personal Insight did not differ between the two conditions, but did not significantly differ from previous experiments’ Personal Insight levels following dream discussion. Experienced and inexperienced participants’ levels of insight were not significantly different. High variability in insight scores indicated that there were large differences between participants in terms of how effective the discussions were for generating insight, but this difference could not be accounted for by experience levels. Insights about changing one’s life correlated with metaphor perception within the dream. These results illustrate the insight-generating potential of dreamwork for some individuals, irrespective of the dreamer’s level of experience, and perhaps suggest that insight for change may come about following perception of metaphors for waking life in the dream.

Practicing counseling and psychotherapy – insights from trainees, supervisors and clients, by Nicholas Ladany, Jessica A. Walker, Lia M. Pate-Carolan, & Laurie Gray Evans, Abingdon, UK, Routledge, ...

Voltage gated potassium ion (Kv) channels regulate action potentials of the nervous system by responding to changes in transmembrane voltage, enabling K+ transport across the membrane to restore cells to their resting potential. Comprised of four identical subunits, Kv channels contain four voltage sensing domains arranged on the periphery of a central pore domain. Each voltage sensor is comprised of four transmembrane helices, numbered S1 through S4. The S4 helix, containing four to six highly-conserved, positively-charged arginine or lysine residues, is responsible for voltage sensitivity in Kv channels. The pore domain consists of two transmembrane helices, S5 and S6. The S5 helix constitutes the periphery of the pore domain and is believed to be relatively immobile. The S6 helices, lining the interior of the channel, gate the protein and regulate K+ permeation. Because each subunit of Kv channels contains six transmembrane helices, they are often referred to as 6TM Kv channels. The depolarization of an action potential is initiated as sodium ions enter the cell. At the cellular resting potential of -70 mV, potassium ion channels are closed, and the S4 helix is in its “down” state. As the electrochemical gradient changes, the S4 helices of Kv channels begin to reorient within the membrane. At the peak of the action potential (roughly +20 mV), the S4 helices exist in their “up” state. This conformational transition of the S4 helix is coupled to the pore domain via the S4-S5 linker, a short, amphipathic helix along the intracellular membrane-water interface. By bridging the C-terminus of the voltage sensor to the N-terminus of the pore domain, the S4-S5 linker couples the voltage sensitivity of the voltage sensor to K+ conduction in the pore domain. Because they begin opening at voltages less than 0 mV, all crystal structures of Kv channels contain an open pore domain. With no structure in the closed conformation, the mechanism of gating in Kv channels remains unclear. Nevertheless, significant biophysical studies have revealed insights into both the closed conformation and the gating transition itself. In this dissertation, I will explore questions relevant to the gating mechanism in voltage gated potassium ion channels through fully-atomistic molecular dynamics (MD) simulations. First, in Chapter 2, I will address the potential role of the 310 helical conformation found in the C-terminal end of S4 in the crystal structures of Kv channels. Spanning eight or more residues, these 310 helices are both uncharacteristically long and conserved in K+ channel crystal structures. By simulating the Kv1.2/2.1 chimera channel’s voltage sensor embedded in a lipid bilayer, I find that an alpha to 310 helical interconversion of the S4 helix reproduces many experimental measurements of the open and closed states of Kv channels. In Chapter 3, I perform molecular dynamics simulations of the entire Kv1.2/2.1 chimera channel. First, I examine the impact of an alpha to 310 helical interconversion of the S4 helix on the pore domain of the channel. Though the results are consistent with the results in Chapter 2 (and the corresponding experimental measurements), I find that this secondary structural modification is insufficient to influence the pore domain of the channel on the timescale of my simulations. In the second half of Chapter 3, I use molecular dynamics simulations to generate a closed state model of the Kv1.2/2.1 chimera from luminescence resonance energy transfer (LRET) measurements of the closed conformation of KvAP. The resulting structure is indeed closed, and also recapitulates a number of experimentally determined measurements of the closed channel. In Chapter 4, I focus on the pore domain. First, using targeted molecular dynamics simulations, I generate a transition between a closed model of the KvAP linker and pore domain to the open conformation. Then, using an umbrella sampling method, I quantify the energetics of the gating transition in KvAP and assess the physiological implications. In agreement with experimental studies of Kv channel energetics, I find that the open pore is roughly 2.7 kcal/mol lower in free energy than the closed conformation. The targeted molecular dynamics and umbrella sampling simulations reveal additional insights into the gating mechanism of KvAP. Lastly, in Chapter 5, I use MD simulations to gain insights into the binding mechanism of VSTx1, a Kv channel inhibitor. By using the experimentally determined neutron scattering density profile of the VSTx1 toxin bound to a lipid bilayer as a restraint for molecular dynamics simulations, I recreate the experimental scattering density profile, and also offer insight into the binding of VSTx1 to a lipid membrane.

Insights into the civic education classroom can be gained through videographic documentation . Videographic material offers, as I argue in this article, great possibilities: Through a reconstructive approach insights into dimensions of civic education such as spatial organisation, symbolic representation and non-verbal communication may emerge. In this way, a deeper understanding of informal political learning in school can be obtained. These aspects have not yet been considered in depth with videographic documentation primarily employed to date in teacher training contexts and lesson evaluation. The case study I present here was inspired by the documentary method and both the potential and limitations of videographic interpretation are discussed in this context. The study also suggests that what is not offered by videographic documentation includes insights into the individual and collective integration of experiences in civic education lessons.

Highly non-ideal solutions are ever-present within chemistry, physics, and materials science – and are characterized by many-body effects across length and timescale. Understanding, and predicting, many-body correlations in the condensed phase is a grand challenge for the modeling and simulation community. Yet within the data science community, a large suite of tools exist for elucidating complex, correlating, relationships amongst variables. Molecular modeling and simulation data is in fact well-suited for study by methods that include the topology of graphs, point cloud data, and recent advances in applied mathematics methods that investigate surfaces like sublevel set persistent homology and geometric measure theory. We adapt, develop, and apply these tools to study highly non-ideal solutions and their interfaces, with examples drawn from separations science. The new physical insight derived from these methods is paving the way for bespoke liquid/liquid interfaces that optimize transport characteristics for purification and synthesis.

Novel coronavirus, SARS-CoV-2, has emerged as one of the deadliest pathogens of this century, creating an unprecedented pandemic Belonging to the betacoronavirus family, it primarily spreads through human contact via symptomatic and asymptomatic transmission Despite several attempts since it emerged, there is no known treatment in the form of drugs or vaccines Hence, work on developing a potential multi-subunit vaccine is the need of the hour In this study, attempts have been made to find globally conserved epitopes from the entire set of SARS-CoV-2 proteins as there is as yet, no clear information on the immunogenicity of these proteins Using diverse computational tools, a ranked list of probable immunogenic, promiscuous epitopes generated through all the three main stages of antigen processing and presentation pathways has been prioritized Moreover, several useful insights were gleaned during these analyses One of the most important insights is that all of the proteins in this pathogen present unique epitopes, so that the targeting of a few specific viral proteins is not likely to result in an effective immune response in humans Due to the presence of these unique epitopes in all of the SARS-CoV-2 proteins, stronger immune responses generated by T cell hyperactivation may lead to cytokine storm and immunopathology and consequently, remote chances of human survival These epitopes, after due validation in vitro, may thus need to be presented to the human body in that form of multi-subunit epitope-based vaccine that avoids such immunopathologies © 2020 The Authors

An analysis of the physical demands of international female soccer match-play and the physical characteristics of elite players

In 1808, King Louis Napoleon had the town hall of Amsterdam converted to Royal Palace. Besides making the necessary architectural alterations, he ordered hundreds of pieces of furniture and other ornamental objects from local furniture makers, upholsterers, decorators and other suppliers. This collection of Empire furniture, which is still preserved in the palace, is today the largest of its kind outside France. Between 2005 and 2009, these pieces of furniture were restored as part of the wider restoration of the entire palace, a gigantic operation that involved hundreds of restoration experts. A furniture committee made sure that quality and looks remained uniform. During the process the restoration experts and researchers made a full study of the furniture, documenting finds and findings, supplemented with research into the origins, the makers, use, techniques and material. This is unique for the Netherlands. The data, recorded in documentation and restoration reports, offer fresh insights in especially the construction and manufacturing process of Dutch Empire furniture. The discoveries are illustrated by a number of purveyances by Carel Breytspraak Sr. (1769-1810), the best paid furniture maker of the king. The 100 chairs he made for the Grand dining room of the palace are an example of pre-modern serial production. This may be inferred from the varying quality of the wood that was used and from the varying thickness of the seat stretchers, among other things. Furthermore, it turned out that the chairs still had the original stuffing, which was reused after having been restored. One chair still had the original upholstery from the days of Louis Napoleon and this was used as the basis for the current upholstery. The chairs are typical examples of furniture made after French decoration prints, which were undoubtedly provided by the king’s architects. The roll-top desk that Breytspraak made for the king’s bedroom is one of the most unique pieces in the collection and is certainly not a mass product. Unlike with the chairs, the mahogany wood used here – mainly applied in mirrored fashion – is of a strikingly high quality. The desk is an example of previous restoration or maintenance efforts. For instance, the marble top as well as the fittings on the lower doors turned out not to be original. This has been remedied in this restoration campaign. Another set of furniture that suffered from previous activities is the corps de bibliotheque. A special aspect here is that for these bookcases – intended for the king’s library and topographical collection – we still have the contract between Breytspraak and the architect, which gives us insight into how the furniture maker was instructed. What is interesting is that Breytspraak was ordered to construct the bookcases in such a way that the shelves could be moved. He was also especially requested to give them a mahogany finish, in such a way that they would have the appearance of massive mahogany. Finally, some small pieces of furniture for the apartment of the crown prince (1809) demonstrate the versatility of Breytspraaks workshop. He produced several gueridons (tripod tables), constructed from a ‘wagon wheel’ carrying a marble top, with a column and a plinth on lion’s feet. These elements are fixed with an iron rod that can be tightened. Further research could provide more insight into the production process and the differences between the Dutch and French furniture.

Collaboration is widely identified as a force for good, with a wide range of benefits attributed to it, but considerable variations exist in descriptions of exactly what constitutes collaboration and how it is undertaken in practice. In the face of this diversity it becomes difficult to understand how effectively the process of collaboration is being undertaken. In this research, value concept principles are adopted in an exploration of collaboration processes in order to derive a better understanding of how organisations establish new collaborations, and to gain insights into the situational factors and human behaviour that may lead to improved collaboration effectiveness. The research design featured a constructivist version of grounded theory used in conjunction with the complementary techniques of Situational Analysis. This design is particularly suited to the research context in which social processes feature prominently and in which the objectives include theory development. A topology of eight generic categories of process is presented in the findings as part of a central category that links temporal, behavioural and situational factors to collaboration outcomes. The identification of social capital and human capital as intermediate forms of value, located in individual actors and their social relationships, is used to highlight the importance of recognising and developing these soft capital forms, if more tangible physical and financial capital is to be generated. Collectively the data emphasise that organisations do not collaborate, people do. Collaboration is fundamentally a social rather than business process. Three dimensions of collaborative compatibility are discussed that recognise the importance of involving competent individuals that are socially compatible if relationships between potentially compatible organisations are to thrive. Organisational compatibility alone will not lead to effective collaboration. This study makes four contributions to existing knowledge. A 3-dimensional model of collaborative compatibility, interpreted in the context of a new typology of collaboration processes, extends existing collaboration theory with insights into the way collaboration relationships form and perform, and the way they are affected by individual and social factors. The recognition of latency in intermediate forms of value makes a contribution to a recognised shortfall in understanding of the temporal dimension of the value literature. In the third, a contribution is made to literature on coopetition and the coordination of inter-firm groups, through the recognition of effective practices in 3rd party brokering organisations. Finally, an incremental contribution is made to the extensive body of knowledge and learning literature through insights into the social factors driving knowledge transfer in inter-organisational groups, and the implications these have for organisational knowledge absorption. These four avenues each have practical implications for how organisations and policy makers plan initiatives to increase economic activity through inter-firm collaboration.

Oxidative processes - insights in reaction mechanisms gained by high resolution and isotope ratio mass spectrometry

Purpose – The purpose of this paper is to provide an interview with Dan Hill, founder and president of Sensory Logic – a research‐based consultancy that specializes in helping to enhance companies' sensory‐emotional connection with customers.

A Design Framework for Personal Learning Environments

First-row transition-metals such as nickel and copper have revolutionized cross-coupling chemistry. Their propensity to form radical intermediates from alkyl electrophiles has greatly expanded the scope of traditional cross-coupling reactions. Alkyl radicals can be recaptured by a chiral transition-metal catalyst allowing for enantioselective bond formation. In general, alkyl radicals rapidly epimerize, and thus both enantiomers of a racemic mixture of an alkyl electrophile can be processed into the same enantiomer of product, rendering the overall process enantioconvergent. Herein, the development of basic bond constructions and the development of asymmetric reactions leveraging alkyl radical intermediates for carbon-nitrogen and carbon-carbon bond formations are discussed. Reaction development is the primary focus of this work, though mechanistic insights discovered along the way are also detailed within. Chapter 2 describes the development of an enantioconvergent alkylation of amine nucleophiles with alkyl electrophiles. Carbazole and indole derivatives are employed as nucleophiles to undergo copper-catalyzed cross-coupling with tertiary α-chloroamide electrophiles under visible light irradiation. Reaction optimization, scope of reactivity, inorganic synthesis, and mechanistic insights are described within. Chapter 3 details the development of a non-asymmetric copper-catalyzed alkylation of aliphatic amines with unactivated alkyl electrophiles under visible light irradiation. The development of a novel catalytic system to circumvent the issues with the photophysical properties of aliphatic amine-copper complexes is discussed. Scope of reactivity and mechanistic investigations are detailed within. Additionally, our efforts to develop an asymmetric variant of this reaction are enclosed. Chapter 4 discusses the development of a copper-catalyzed alkylation of N-heterocycles with α-halolactams in the absence of light. The scope of the reactivity is detailed within. Mechanistic studies contained in this section suggest a unique and interesting reaction pathway—one that does not proceed through a radical intermediate. Chapter 5 presents a novel class of organosilane electrophiles employed in an enantioconvergent nickel-catalyzed cross-coupling reaction. Here, the development of the reaction, scope of reactivity, and initial mechanistic insights are discussed.