How do grazers achieve their distribution? A continuum of models from random diffusion to the ideal free distribution using biased random walks

A conceptual model is described for generating distributions of grazing animals, according to their searching behavior, to investigate the mechanisms animals may use to achieve their distributions. The model simulates behaviors ranging from random diffusion, through taxis and cognitively aided navigation (i.e., using memory), to the optimization extreme of the Ideal Free Distribution. These behaviors are generated from simulation of biased diffusion that operates at multiple scales simultaneously, formalizing ideas of multiple-scale foraging behavior. It uses probabilistic bias to represent decisions, allowing multiple search goals to be combined (e.g., foraging and social goals) and the representation of suboptimal behavior. By allowing bias to arise at multiple scales within the environment, each weighted relative to the others, the model can represent different scales of simultaneous decision-making and scale-dependent behavior. The model also allows different constraints to be applied to the animal's ability (e.g., applying food-patch accessibility and information limits). Simulations show that foraging-decision randomness and spatial scale of decision bias have potentially profound effects on both animal intake rate and the distribution of resources in the environment. Spatial variograms show that foraging strategies can differentially change the spatial pattern of resource abundance in the environment to one characteristic of the foraging strategy.</

Inscribing value on business model innovations: Insights from industrial projects commercializing disruptive digital innovations

In this paper we seek to show how marketing activities inscribe value on business model innovation, representative of an act, or sequence of socially interconnecting acts. Theoretically we ask two interlinked questions: (1) how can value inscriptions contribute to business model innovations? (2) how can marketing activities support the inscription of value on business model innovations? Semi-structured in-depth interviews were conducted with the thirty-seven members from across four industrial projects commercializing disruptive digital innovations. Various individuals from a diverse range of firms are shown to cast relevant components of their agency and knowledge on business model innovations through negotiation as an ongoing social process. Value inscription is mutually constituted from the marketing activities, interactions and negotiations of multiple project members across firms and functions to counter destabilizing forces and tensions arising from the commercialization of disruptive digital innovations. This contributes to recent conceptual thinking in the industrial marketing literature, which views business models as situated within dynamic business networks and a context-led evolutionary process. A contribution is also made to debate in the marketing literature around marketing's boundary-spanning role, with marketing activities shown to span and navigate across functions and firms in supporting value inscriptions on business model innovations.

Distinct CCK-2 Receptor Conformations Associated with β-Arrestin-2 Recruitment or Phospholipase-C Activation Revealed by a Biased Antagonist

Seven-transmembrane receptors (7TMRs), also termed G protein-coupled receptors (GPCRs), form the largest class of cell surface membrane receptors, involving several hundred members in the human genome. Near 30% of marketed pharmacological agents target 7TMRs. 7TMRs adopt multiple conformations upon agonist binding. Biased agonists, in contrast to non-biased agonists, are believed to stabilize conformations preferentially activating either G-protein- or ß-arrestin-dependent signalling pathways. However, proof that cognate conformations of receptors display structural differences within their binding site where biased agonism initiates, are still lacking. Here, we show that a non-biased agonist, cholecystokinin (CCK) induces conformational states of the CCK2R activating Gq-protein-dependent pathway (CCK2RG) or recruiting ß-arrestin2 (CCK2Rß) that are pharmacologically and structurally distinct. Two structurally unrelated antagonists competitively inhibited both pathways. A third ligand (GV150,013X), acted as a high affinity competitive antagonist on CCK2RG but was nearly inefficient as inhibitor of CCK2Rß. Several structural elements on both GV150,013X and in CCK2R binding cavity, which hinder binding of GV150,013X only to the CCK2Rß were identified. At last, proximity between two conserved amino acids from transmembrane helices 3 and 7 interacting through sulphur-aromatic interaction was shown to be crucial for selective stabilization of the CCK2Rß state. These data establish structural evidences for distinct conformations of a 7TMR associated with ß-arrestin-2 recruitment or G-protein coupling and validate relevance of the design of biased ligands able to selectively target each functional conformation of 7TMRs.

A self-learning algorithm for biased molecular dynamics

A new self-learning algorithm for accelerated dynamics, reconnaissance metadynamics, is proposed that is able to work with a very large number of collective coordinates. Acceleration of the dynamics is achieved by constructing a bias potential in terms of a patchwork of one-dimensional, locally valid collective coordinates. These collective coordinates are obtained from trajectory analyses so that they adapt to any new features encountered during the simulation. We show how this methodology can be used to enhance sampling in real chemical systems citing examples both from the physics of clusters and from the biological sciences.

Simulations of Biased Agonists in the β2 Adrenergic Receptor with Accelerated Molecular Dynamics

The biased agonism of the G protein-coupled receptors (GPCRs), where in addition to a traditional G protein-signalling pathway a GPCR promotes intracellular signals though ß-arrestin, is a novel paradigm in pharmacology. Biochemical and biophysical studies have suggested that a GPCR forms a distinct ensemble of conformations signalling through the G protein and ß-arrestin. Here we report on the dynamics of the ß2 adrenergic receptor bound to the ß-arrestin and G protein biased agonists and the empty receptor to further characterize the receptor conformational changes caused by biased agonists. We use conventional and accelerated molecular dynamics (aMD) simulations to explore the conformational transitions of the GPCR from the active state to the inactive state. We found that aMD simulations enable monitoring the transition within the nanosecond timescale while capturing the known microscopic characteristics of the inactive states, such as the ionic lock, the inward position of F6.44, and water clusters. Distinct conformational states are shown to be stabilized by each biased agonist. In particular, in simulations of the receptor with the ß-arrestin biased agonist, N-cyclopentylbutanepherine we observe a different pattern of motions in helix 7 when compared to simulations with the G protein biased agonist, Salbutamol that involves perturbations of the network of interactions within the NPxxY motif. Understanding the network of interactions induced by biased ligands and the subsequent receptor conformational shifts will lead to development of more efficient drugs. © 2013 American Chemical Society

Knowledge work: Gender-blind or gender-biased?

Knowledge-intensive firms (KIFs) have been the subject of growing interest from researchers. However, investigations into the comparative experiences of men and women in KIFs remain sparse, and little is known about women's participation in the processes of innovation and knowledge exchange and combination that are core features of KIFs. The article reports on the findings of a study in the UK and Ireland involving 498 male and female knowledge workers in KIFs. Despite equal levels of qualification and experience, women are more likely to be in lower status and less secure jobs. They also predominantly occupy roles featuring less variety and autonomy than men and, despite comparable levels of knowledge exchange and combination, are less likely to be in a position to translate this into the innovative work behaviours necessary for career advancement. The findings suggest that women's experiences of and participation in knowledge processes within KIFs differ fundamentally from men's. © The Author(s) 2012.

An exploration of business model development in the commercialization of technology innovations

Research on business model development has focused on the relationships between elements of value conceptualization and organization having a linear sequence in which business models are first designed and then implemented. Another stream of research points to business model development with these elements interacting in a cyclical manner. There is a need to improve our understanding of the connective mechanisms and dynamics involved in business model development, particularly from the challenging perspective of commercializing innovations. The aim of this paper was to explore business model development during the commercialization of innovations through a case-based qualitative study. This study found from four case studies that specific elements of business model development, representative of the conceptualization of value and organizing for value creation, integrate in a dynamic and cyclical process in the commercialization of technology innovations. The study provides empirical evidence that adds new insights to literature on sequential and more interactive processes of business model development. It also contributes to literature on business model development and particularly how it relates to the commercialization of innovations.

Pulsed second harmonic generation by stacks of magnetically biased semiconductor layers

The pulsed second harmonic generation (SHG) by periodic stacks of nonlinear semiconductor layers with external magnetic bias has been studied in the self-consistent problem formulation, taking into account mobility of carriers. The products of nonlinear scattering in the three-wave mixing process are examined. It is demonstrated that the waveform evolution in magnetoactive weakly nonlinear semiconductor periodic structure illuminated by Gaussian pulse is strongly affected by the magnetic bias and collision frequency of the carriers. The effect of nonreciprocity on the SHG efficiency is discussed and illustrated by the examples. © 2013 European Microwave Association.

Report on the 2014 UKONS Annual Conference Belfast, 14–15 November 2014: focus on living with and beyond cancer, patient information and support, and innovations in treatment and care

The UK Oncology Nursing Society’s (UKONS) annual conference focused on three major themes. These were ‘Living With and Beyond Cancer’, ‘Patient Information and Support’, and ‘Innovations in Treatment and Care’. It featured a wide range of presentations, industry satellites, exhibitions, poster discussions. and workshops. Presenters ranged from those eminent in their particular field to those gracing the speaker’s podium for the first time. The rich variety of presentations covered policy, cancer trends, clinical developments, care initiatives, personal development, and advances in practice. There was a strong emphasis on skills, knowledge, values, and attitudes, with the most junior and novice nurses mixing with experienced and highly esteemed practitioners.