What affords being creative? Opportunities for novelty in light of perception, embodied activity, and imaginative skill.

An affordance perspective highlights how resourceful the ecology is for creative actions of all sorts; it captures how creativity is grounded in materiality. In contrast to "canonical affordances" (i.e., "ready-to-hand," mundane instances), creative affordances point to unconventional or surprising action opportunities that are nonetheless valued. Our initial aim is to discuss how to frame the affordance concept to make it attractive for the study of creativity. We propose a dialectic position that reconciles aspects of the realism of ecological psychology with the constructivist view more typical of creativity scholars. We stress that novel options frequently depend on constructive actions; novelty cannot always simply be "found" or just waits to be used. Many creative opportunities only emerge from how person actively engages with the ecology. Our second aim is to explore specific ways that creativity is mediated through affordances, based on illustrations from crafts and dance. These suggest that affordances span various timescales and mediate in multiple ways, from noticing existing potentials, via active affordance shaping, to background activities that indirectly invite or enable novelty. In conclusion we discuss how a person's creative "vision," imagination and combinatoric ability, all fundamental creativity mechanisms, relate to affordances and how fruitful creative directions may be perceptually hinted at.

Complexity Regulation Competencies: A Naturalistic Framework.

This article presents a framework to describe how professional experts regulate complex adaptive systems (CAS), a skill found across bio-psychological, ecological, technical, and social contexts. The regulation aim is to facilitate and constrain the self-organization of a CAS; regulators engage in dynamic decision making while the system evolves. While many naive regulators are overtaxed when they encounter nonlinear and multi-causal dynamics, less is known about how experts perform. I argue that a rich set of competencies can make expert performance distinctive. The basic sensitivities for CAS that shape the general philosophy of practice and a role identity as process facilitators provide some foundation. Turning this into an applied skill set, however, additionally requires (a) the creation of mediating interfaces with a 'target' CAS, (b) interaction skills for exploring and stimulating the CAS, (c) the use of domain knowledge about the system's nature and structure for conceptualizing its state as well as dynamics, (d) the use of analogical reasoning, categories, heuristics, and models to make 'if-then' inferences from systemic problem constellations to holistic strategies, and (e) synoptic and meta-regulative capabilities that allow supervising the mix of deployed resources relative to the demands of ongoing task. These CAS regulation tools mesh in variable ways and can mutually amplify each other, i.e. synergize. Illustrations for the framework come from two somatic therapies (aka bodywork), the Shiatsu and Feldenkrais methods, in which therapists use manual techniques as a regulatory means to help their clients.

Probing the Conformation of an IgG1 Monoclonal Antibody in Lyophilized Solids Using Solid-State Hydrogen-Deuterium Exchange with Mass Spectrometric Analysis (ssHDX-MS).

Therapeutic proteins are often formulated as lyophilized products to improve their stability and prolong shelf life. The stability of proteins in the solid-state has been correlated with preservation of native higher order structure and/or molecular mobility in the solid matrix, with varying success. In the studies reported here, we used solid-state hydrogen-deuterium exchange with mass spectrometric analysis (ssHDX-MS) to study the conformation of an IgG1 monoclonal antibody (mAb) in lyophilized solids and related the extent of ssHDX to aggregation during storage in the solid phase. The results demonstrate that the extent of ssHDX correlated better with aggregation rate during storage than did solid-state Fourier-transform infrared (ssFTIR) spectroscopic measurements. Interestingly, adding histidine to sucrose at different formulation pH conditions decreased aggregation of the mAb, an effect that did not correlate with structural or conformational changes as measured by ssFTIR or ssHDX-MS. Moreover, peptide-level ssHDX-MS analysis in four selected formulations demonstrated global changes across the structure of the mAb when lyophilized with sucrose, trehalose, or mannitol, whereas site-specific changes were observed when lyophilized with histidine as the sole excipient.

Probing Conformational Diversity of Fc Domains in Aggregation-Prone Monoclonal Antibodies.

PURPOSE: Fc domains are an integral component of monoclonal antibodies (mAbs) and Fc-based fusion proteins. Engineering mutations in the Fc domain is a common approach to achieve desired effector function and clinical efficacy of therapeutic mAbs. It remains debatable, however, whether molecular engineering either by changing glycosylation patterns or by amino acid mutation in Fc domain could impact the higher order structure of Fc domain potentially leading to increased aggregation propensities in mAbs. METHODS: Here, we use NMR fingerprinting analysis of Fc domains, generated from selected Pfizer mAbs with similar glycosylation patterns, to address this question. Specifically, we use high resolution 2D [13C-1H] NMR spectra of Fc fragments, which fingerprints methyl sidechain bearing residues, to probe the correlation of higher order structure with the storage stability of mAbs. Thermal calorimetric studies were also performed to assess the stability of mAb fragments. RESULTS: Unlike NMR fingerprinting, thermal melting temperature as obtained from calorimetric studies for the intact mAbs and fragments (Fc and Fab), did not reveal any correlation with the aggregation propensities of mAbs. Despite >97% sequence homology, NMR data suggests that higher order structure of Fc domains could be dynamic and may result in unique conformation(s) in solution. CONCLUSION: The overall glycosylation pattern of these mAbs being similar, these conformation(s) could be linked to the inherent plasticity of the Fc domain, and may act as early transients to the overall aggregation of mAbs.

Ortho group activation of a bromopyrrole ester in Suzuki-Miyaura cross-coupling reactions: Application to the synthesis of new microtubule depolymerizing agents with potent cytotoxic activities.

New microtubule depolymerizing agents with potent cytotoxic activities have been prepared with a 5-cyano or 5-oximino group attached to a pyrrole core. The utilization of ortho activation of a bromopyrrole ester to facilitate successful Suzuki-Miyaura cross-coupling reactions was a key aspect of the synthetic methodology. This strategy allows for control of regiochemistry with the attachment of four completely different groups at the 2, 3, 4 and 5 positions of the pyrrole scaffold. Biological evaluations and molecular modeling studies are reported for these examples.

Formyl Group Activation of a Bromopyrrole Ester in Suzuki Cross-Coupling Reactions: Application to a Formal Synthesis of Polycitone A and B and Polycitrin A.

A new pyrrole building block is described, which allows for the regiospecific synthesis of 2,3,5-trisubstituted pyrroles and 2,3,4,5- tetrasubstituted pyrroles. Optimization studies are presented for the preparation of the pyrrole building block along with the evaluation of various cross-coupling conditions and cross-coupling agents. A short, formal synthesis of the natural products Polycitone A, Polycitone B and Polycitrin A from the pyrrole building block is also described.

An "in vivo" analysis of crafts practices and creativity-Why affordances provide a productive lens.

Scholars are increasingly recognizing that creativity is grounded in the active sensorimotor engagement with the environment and materiality. Affordances-recognizable pointers to action opportunities in the ecology-provide a helpful prism for analyzing how this happens. Creative practitioners, as they seek aesthetic opportunities or innovation, depend on their sensitivity toward potentialities in their action space. Presently, we apply a high-zoom lens to a crafts process, giving our micro-genetic research design an affordance focus. By investigating one of the authors, a ceramicist and a practitioner-researcher, through her process of making of a vase, we tracked how affordances are responded to, developed, shaped, invited or, where necessary, rejected, as the ceramicist "routes" her creative trajectory. Several insights emerge: (1) The ceramicist's decisions-initially about general directions, then about aesthetic details-unfold while engaging with the clay; they emerge in stepwise fashion, but with a holistic orientation. (2) Choosing among affordances requires parallel sensitivities to object functionality, aesthetics and creativity, as well as technical feasibility; adhering to the proper technical procedure that provides the very basis for creatively relevant affordances to later arise. (3) While the hands and eyes engage with short-lived affordances the ceramicist must keep in view higher-timescale affordances that ensure a good task progression for making a vase, and affordances for the material's overall "workability". (4) The ceramicist typically relates to momentary affordances in light of expected as well as imagined others, to ensure a coherent end product. (5) Affordances contribute to material creativity in more ways than typically recognized in the literature. They range from serendipitous "finds" to options developed with a large degree of creative autonomy; affordances may also be indirectly invited and practitioners strategically change probability distributions as well as providing an enabling background for generative action. Thus, a crafts practitioner brings forth unconventional affordances through active engagement, using a mix of exploration, strategy, and imaginative potential. Affordance theorists err when stressing the possibility to just "find" creative options or that perceptual acuity is the sole skill.

The anatomy of antagonistic coregulation: Emergent coordination, path dependency, and the interplay of biomechanic parameters in Aikido.

Using a video-supported cognitive ethnographic and phenomenological approach, we address the interactively generated dynamic of bouts in Aikido. This "soft" martial art enables a defender to blend with and then redirect an attacker's aggressive energy so as to break his balance, while preserving an ethos of non-violence, mutuality, and respect. Our analysis explores the skills used to minutely adapt to the opponent, the causal-temporal structure of Aikido, notably the cumulative effect build-up and main decision points in a bout, as well as the perceptual cues from inter-body geometry, timing, and force dynamics that inform decisions. We then contrast different interaction scenarios by focusing on micro-events that shape defensive preferences. For a successful defense, technical modulations or even the preferred technique itself can be selected as the interaction unfolds ("decision-making-in-action"). For a closer look, we analyze the interplay of multiple parameters: flexibility of intention (i.e. early deciding vs. keeping options openlonger), technique (i.e. type of lever or throw), initial body symmetry, step combinations, spacing and timing relative to the attacker, degree of force, as well as possible skill differentials. We describe complex interdependencies between these parameters, which can be balanced in various ways as agents respond to the interaction dynamic.

Sources of Embodied Creativity: Interactivity and Ideation in Contact Improvisation.

Drawing on a micro-phenomenological paradigm, we discuss Contact Improvisation (CI), where dancers explore potentials of intercorporeal weight sharing, kinesthesia, touch, and momentum. Our aim is to typologically discuss creativity related skills and the rich spectrum of creative resources CI dancers use. This spectrum begins with relatively idea-driven creation and ends with interactivity-centered, fully emergent creation: (1) Ideation internal to the mind, the focus of traditional creativity research, is either restricted to semi-independent dancing or remains schematic and thus open to dynamic specification under the partner’s influence. (2) Most frequently, CI creativity occurs in tightly coupled behavior and is radically emergent. This means that interpersonal synergies emerge without anybody’s prior design or planned coordination. The creative feat is interpersonally “distributed” over cascades of cross-scaffolding. Our micro-genetic data validate notions from dynamic systems theory such as interpersonal self-organization, although we criticize the theory for failing to explain where precisely this leaves skilled intentionality on the individuals’ part. Our answer is that dancers produce a stream of momentary micro-intentions that say “yes, and”, or “no, but” to short-lived micro-affordances, which allows both individuals to skillfully continue, elaborate, tweak, or redirect the collective movement dynamics. Both dancers can invite emergence as part of their playful exploration, while simultaneously bringing to bear global constraints, such as dance scores, and guide the collective dynamics with a set of specialized skills we shall term emergence management.

Single-site ventricular and biventricular pacing: investigation of latest depolarization strategy.

Aims Cardiac resynchronization therapy with biventricular pacing has proved beneficial in symptomatic heart failure patients, yet the effects in patients with structurally normal hearts remain unknown. We hypothesized that, in an acute swine model with normal anatomy and function, single-site right ventricular (RV) pacing would better preserve haemodynamic function and electrical activation compared to biventricular pacing. Methods Endocardial single-site pacing was performed in anesthetized swine (n = 7) from the RV septum and RV apex. Biventricular pacing was performed using an epicardial left ventricular (LV) lead and a RV lead. High-resolution, non-contact mapping was employed to record LV activation sequences simultaneously with haemodynamic data after 5 min of consistent capture. Results All pacing interventions significantly prolonged QRS and total endocardial activation durations (P < 0.05) compared to intrinsic activation. Biventricular pacing with the RV apex lead significantly impaired LV systolic mechanics (dP/dt(max), max LV pressure; P < 0.05), and reduced LV relaxation to the greatest extent (dP/dt(min), P = ns). Right ventricular septal pacing conserved function better than other pacing interventions (P = ns) and elicited an intrinsic electrical activation sequence. Conclusion In intact, synchronous hearts, acute biventricular pacing resulted in systolic dysfunction and abnormal LV electrical activation.

Bodywork as systemic and inter-enactive competence: participatory process management in Feldenkrais® Method and Zen Shiatsu.

Feldenkrais and Shiatsu enable somatic learning through continuous tactile coupling, a real-time interpersonal dynamic unfolding in a safe dyadic sphere. The first part of our micro-ethnographic study draws on process vignettes and subjective theories to demonstrate how bodywork is infused with systemic sensitivities and awareness for non-linear process management. Expressed in dynamic systems parlance, both disciplines foster metastability, adaptivity, and self-organization in the client's somato-personal system by progressively reconfiguring systemic dispositions, i.e., an attractor landscape. Doing so requires a keen embodied apperception of hierarchies of somato-systemic order. Bodyworkers learn to explore these in their eigenfunction (joints, muscles, fascia), discriminate coordinative organization in small ensembles, and monitor large-scale dynamic interplay. The practitioner's "extended body" reaching forth into the client's through a resonance loop eventually becomes part of this. Within a bodywork session, practitioners modulate this hierarchical functional architecture. Their ability for sensorially staying apace of systemic emergence allows them to respond to minute changes and customize reactions in a zone of proximal development (dynamic immediacy). They stimulate the client's system with a mix of perturbing and stabilizing interventions that oscillate between eigenfunctions and their coordinative integration. Practical knowledge for "soft-assembling" non-linear synergies is crucial for this (cumulative local effects, high-level functions "slaving" the system, etc.). The paper's second part inventorizes the bodyworker's operative tool-box-micro-skills providing the wherewithal for context-intelligent intervention. Practitioners deploy "educated senses" and a repertoire of hands-on techniques (grips, stretches, etc.) against a backdrop of somatic habits (proper posture, muscle activation, gaze patterns, etc.). At this level, our study addresses a host of micro-skills through the lens of enactive cognitive science.