Mechanism-based Theory Research Articles

A mechanism-based theory of cellular and tissue plasticity.

Plastic deformation in cells and tissues has been found to play crucial roles in collective cell migration, cancer metastasis, and morphogenesis. However, the fundamental question of how plasticity is initiated in individual cells and then propagates within the tissue remains elusive. Here, we develop a mechanism-based theory of cellular and tissue plasticity that accounts for all key processes involved, including the activation and development of active contraction at different scales as well as the formation of endocytic vesicles on cell junctions and show that this theory achieves quantitative agreement with all existing experiments. Specifically, it reveals that, in response to optical or mechanical stimuli, the myosin contraction and thermal fluctuation-assisted formation and pinching of endocytic vesicles could lead to permanent shortening of cell junctions and that such plastic constriction can stretch neighboring cells and trigger their active contraction through mechanochemical feedbacks and eventually their plastic deformations as well. Our theory predicts that endocytic vesicles with a size around 1 to 2 µm will most likely be formed and a higher irreversible shortening of cell junctions could be achieved if a long stimulation is split into multiple short ones, all in quantitative agreement with experiments. Our analysis also shows that constriction of cells in tissue can undergo elastic/unratcheted to plastic/ratcheted transition as the magnitude and duration of active contraction increases, ultimately resulting in the propagation of plastic deformation waves within the monolayer with a constant speed which again is consistent with experimental observations.

How to phrase critical realist interview questions in applied social science research

ABSTRACT The tenets of critical and social realism are well supported in the literature. However, researchers following a realist paradigm have concerns about the lack of methodical guidance for qualitative interviewing, despite their affirmation about the importance of in-depth interviews. A conducted review of empirical realist literature provides evidence of an absence of guidance and commonality regarding interview planning practices. To overcome this absence, this paper composes a guiding framework to assist researchers to phrase more appropriate interview questions in realist research. The steps are founded on critical and social realist concepts while guided by methodological realist principles. Its contribution aims to not only improve the practice of realist inquiry methods but also to introduce more research transparency. A more transparent method for interview questions can lead to increased validity and afford replicability of mechanism-based theories resulting from empirical realist research.

Examining the Application of Retroductive Theorizing in Realist-Informed Studies

Introduction: Transcendental realism, the philosophical perspective dealing with the existence of causal powers governed by universal laws of nature, provides a useful framework for research conducted in the social sciences, including the field of health policy and systems research. Transcendental realism has been criticized, however, for offering weak methodological guidance for conducting research. Consequently, realist-informed studies are deemed to be less robust and less transparent, particularly regarding data analysis and synthesis towards evidence generation. In particular, the extent to which retroductive theorizing, the central evidence generating activity in realist-informed research is applied remains unclear, mysterious, and esoteric. We aimed to examine the extent to which retroductive theorizing is applied and described in realist-informed studies. Methods: We conducted a summative content analysis of 311 manuscripts included in this study. The analysis involved the counting and comparisons of the four forms of inference-making methods namely deduction, induction, abduction, and retroduction. This was followed by interpretation of the underlying context in which they were used, for example, the identification and linking of relevant constructs towards the formulation of mechanism-based theories. Findings: We found that the explicit application and description of retroductive theorizing in realist-informed studies remain minimal and inadequate. Abductive reasoning was reported in only 09/311 (2.9%) of the studies while retroduction was reported in [21/311 (6.8%)]. Abduction and retroduction, although central to realist-informed research, are seldom explicitly applied and described in such studies whereas deduction and induction, while they are meant to support retroductive theorizing, continue to dominate the process of theory formulation. Conclusion: While retroductive theorizing is less formulaic, this study highlights further methodological inadequacies within realist-informed studies. We acknowledge that it is difficult to describe inferential logic in the abstract, but recommend that realist researchers should makes their retroductive theorizing an explicit activity illustrating their critical steps in concrete applications for improved transparency and trustworthiness.

Theorising business model innovation: An integrated literature review

The aim of this article is to theorise the business model innovation (BMI) phenomenon as we explore why and how BMI occurs, specifically to answer the question, What are the mechanisms involved? We evaluate extant research by adapting the context-intervention-mechanism-output framework, and adopting a mechanism-based theory building approach for synthesising our findings. This study makes three contributions: first, we enrich epistemology by adopting a process view as we show that BMI is a series of interdependent mechanisms. Second, we identify six mechanisms unique to the phenomenon. Third, we offer a prescient outlook of BMI change as a metatheory.JEL Classifications: M10, O30, O31, O39

Qualitative metabolomics profiling of serum and bile from dogs with gallbladder mucocele formation.

Mucocele formation is characterized by secretion of abnormally thick mucus by the gallbladder epithelium of dogs that may cause obstruction of the bile duct or rupture of the gallbladder. The disease is increasingly recognized and is associated with a high morbidity and mortality. The cause of gallbladder mucocele formation in dogs is unknown. There is a strong breed predisposition and affected dogs have a high incidence of concurrent endocrinopathy or hyperlipidemia. These observations suggest a significant influence of both genetic and metabolic factors on disease pathogenesis. In this study, we investigated a theory that mucocele formation is associated with a syndrome of metabolic disruption. We surmised that a global, untargeted metabolomics approach could provide unique insight into the systemic pathogenesis of gallbladder mucocele formation and identify specific compounds as candidate biomarkers or treatment targets. Moreover, concurrent examination of the serum and hepatic duct bile metabolome would enable the construction of mechanism-based theories or identification of specific compounds responsible for altered function of the gallbladder epithelium. Abnormalities observed in dogs with gallbladder mucocele formation, including a 33-fold decrease in serum adenosine 5’-monophosphate (AMP), lower quantities of precursors required for synthesis of energy transporting nucleotides, and increases in citric acid cycle intermediates, suggest excess metabolic energy and a carbon surplus. Altered quantities of compounds involved in protein translation and RNA turnover, together with accumulation of gamma-glutamylated and N-acetylated amino acids in serum suggest abnormal regulation of protein and amino acid metabolism. Increases in lathosterol and 7α-hydroxycholesterol suggest a primary increase in cholesterol synthesis and diversion to bile acid formation. A number of specific biomarker compounds were identified for their ability to distinguish between control dogs and those that formed a gallbladder mucocele. Particularly noteworthy was a significant decrease in quantity of biologically active compounds that stimulate biliary ductal fluid secretion including adenosine, cAMP, taurolithocholic acid, and taurocholic acid. These findings support the presence of significant metabolic disruption in dogs with mucocele formation. A targeted, quantitative analysis of the identified serum biomarkers is warranted to determine their utility for diagnosis of this disease. Finally, repletion of compounds whose biological activity normally promotes biliary ductal secretion should be examined for any therapeutic impact for resolution or prevention of mucocele formation.

"The network dynamics of attention in organizations: Mechanisms, models and empirical results"

We propose a mechanism-based theory of attention that explains how the structure of organizational attention networks emerges from time ordered sequences of interdependent acts of attention allocat...

"Parallel Investments, Agency Theory, and Performance of New Ventures: a Mechanism-Based Approach"

Management studies rarely state what they mean by “theory”. Yet, theory is required for scientific generalizations beyond basic generalizations from sample to population. The study provides an example of how the mechanism-based approach to scientific theories can be used in the context of management research to address the generalization problem. I employ agency theory to draw hypotheses about performance of new ventures receiving funding from venture capital investors with equity stakes in competing ventures. Hypotheses are tested in a cross-industry sample of US-based ventures founded between 1995 and 2014. The paper demonstrates how the mechanism-based theory supports generalizations of empirical findings, and how it allows empirical findings to support generalizations of the theory.

Receptivity, reactivity and the successful psychopath

I argue that psychopathy undermines three common assumptions typically invoked in favor of moderate reasons responsive theories of moral responsibility. First, I propose a theory of psychopathic agency and claim that psychopathic agency suggests that the systems underlying receptivity to reason bifurcate into at least two sub-systems of receptivity. Next, I claim that the bifurcation of systems for receptivity suggests that reactivity is not “all of a piece” but that it too decomposes into at least two sub-systems. Lastly, I argue that prior attempts by Fischer and Ravizza to address these concerns contain an appeal to internalism. Since Fischer and Ravizza want their theory to remain agnostic about the nature of reasons for action, this appeal to internalism is problematic for their view. I close by suggesting that if we are to make sense of when and why psychopaths are responsible then a mechanism-based theory of responsibility must be able to explain how different systems of receptivity and reactivity come together to constitute a single mechanism that grounds responsibility ascriptions for action and they must do so without tacitly appealing to implausible forms of internalism about reasons for action.

Two-scale mechanism-based theory of nonlinear viscoelasticity

The paper presents a mechanism-based two-scale theory for a generalized nonlinear viscoelastic continuum. The continuum is labeled as generalized since it contains extra degrees of freedom typical of past high-order continuum theories, though a new formulation is presented here tailored to meet the needs of the physical description of the viscoelastic solid. The microstress that appears in the equations, often criticized for a lack of physical meaning, is assigned in this work to viscous free chains superimposed on a nonlinear elastic backbone composed of crosslinks and reinforcement. Mathematically, hyperelasticity is used to describe the equilibrium backbone (macroscale), and an improvement of tube models for reptation dynamics describes the free chain motion at the microscale. Inhomogeneous deformation is described by inclusion of a microstrain gradient into the formulation. Thus, the theory is nicely suited for materials with microstructure where localization of strains and inhomogeneous deformation occur in addition to viscoelastic damping mechanisms due to free chains. Besides the microstress, physical meaning of the additional boundary conditions arising in the general theory is also presented. Since the proposed material model is mechanism-based, macroscopic performances are functions of microstructural variables describing the polymer chemistry so that parametric material design concepts may be gleaned from the model. Several physical phenomena are captured through numerical simulation of the class of materials of interest: size effects, strain localization, and the fracture process. Results agree qualitatively with both experimental data and direct numerical simulation for filled elastomeric solids.

Interorganizational Routines: Imprinting and Coordinating R&D Practices in International Alliances

While routines within organizations have been at the core of research on organizational stability and change for decades, the scholarly interest in interorganizational routines is much more recent – despite the continued interest in interorganizational relations and networks. Notwithstanding first efforts to understand interorganizational routines, it is still unclear how these emerge from intraorganizational routines and develop over time. To answer this research question, we refer to recent attempts to balance agency and structure in research on intraorganizational routines by adopting a practice-based conceptualization informed by structuration theory. More importantly, we apply and extend the idea of imprinting and reveal the underlying mechanisms that cause the stabilization or modification of routines at the in-terorganizational level. Using an in-depth case study of an international R&D joint venture, the imprinting and development of a set of coordinating routines aimed at aligning the diverse practices of the R&D units of the two parent companies is delineated. The study contributes to a more balanced and contextual but also more mechanism-based theory of interorganizational routines structuration.

Instabilities Across the Isotropic Conductivity Point in a Nematic Phenyl Benzoate under AC Driving

We characterize the sequence of bifurcations generated by ac fields in a nematic layer held between unidirectionally rubbed ITO electrodes. The material, which possesses a negative dielectric anisotropy epsilona and an inversion temperature for electrical conductivity anisotropy sigmaa, exhibits a monostable tilted alignment near TIN, the isotropic-nematic point. On cooling, an anchoring transition to the homeotropic configuration occurs close to the underlying smectic phase. The field experiments are performed for (i) negative sigmaa and homeotropic alignment, and (ii) weakly positive sigmaa and nearly homeotropic alignment. Under ac driving, the Freedericksz transition is followed by bifurcation into various patterned states. Among them are the striped states that seem to belong to the dielectric regime and localized hybrid instabilities. Very significantly, the patterned instabilities are not excited by dc fields, indicating their possible gradient flexoelectric origin. The Carr-Helfrich mechanism-based theories that take account of flexoelectric terms can explain the observed electroconvective effects only in part.

Explaining Social Change: An Analytical Approach

La sociologia analítica és una aproximació a la teorització social «d’abast mitjà» que intenta desenvolupar explicacions precises, realistes i basades en l’acció sobre diversos fenòmens socials. En el nucli de l’enfocament analític es troba la idea que les explicacions acceptables han d’explicar els mecanismes a través dels quals es van produir els fenòmens que es volen explicar. En aquest article discutim els elements més importants d’aquest enfocament i intentem il·lustrar els diversos components que integren l’explicació del canvi social. L’enfocament analític adoptat busca integrar d’una manera estreta les teories de l’acció i de la interacció basades en mecanismes amb els models computacionals basats en agents. L’article s’organitza de la manera següent: 1. Presentem les idees guia que hi ha al darrere de l’enfocament dels mecanismes. 2. Discutim diversos mecanismes d’acció i interacció amb l’objectiu d’il·lustrar com funciona l’enfocament. 3. Utilitzem un model basat en l’agència per il·lustrar com poden vincular-se els mecanismes de nivell individual amb els resultats socials. 4. Mostrem la importància de calibrar empíricament aquest tipus de models. 5. Acabem amb unes observacions finals.

Simple rules yield complex food webs.

Several of the most ambitious theories in ecology describe food webs that document the structure of strong and weak trophic links that is responsible for ecological dynamics among diverse assemblages of species. Early mechanism-based theory asserted that food webs have little omnivory and several properties that are independent of species richness. This theory was overturned by empirical studies that found food webs to be much more complex, but these studies did not provide mechanistic explanations for the complexity. Here we show that a remarkably simple model fills this scientific void by successfully predicting key structural properties of the most complex and comprehensive food webs in the primary literature. These properties include the fractions of species at top, intermediate and basal trophic levels, the means and variabilities of generality, vulnerability and food-chain length, and the degrees of cannibalism, omnivory, looping and trophic similarity. Using only two empirical parameters, species number and connectance, our 'niche model' extends the existing 'cascade model and improves its fit ten-fold by constraining species to consume a contiguous sequence of prey in a one-dimensional trophic niche.

Mechanism-based strain gradient plasticity—II. Analysis

A mechanism-based theory of strain gradient (MSG) plasticity has been proposed in Part I of this paper. The theory is based on a multiscale framework linking the microscale notion of statistically stored and geometrically necessary dislocations to the mesoscale notion of plastic strain and strain gradient. This theory is motivated by our recent analysis of indentation experiments which strongly suggest a linear dependence of the square of plastic flow stress on strain gradient. Such a linear dependence is consistent with the Taylor plastic work hardening model relating the flow stress to dislocation density. This part of this paper provides a detailed analysis of the new theory, including equilibrium equations and boundary conditions, constitutive equations for the mechanism-based strain gradient plasticity, and kinematic relations among strains, strain gradients and displacements. The theory is used to investigate several phenomena that are influenced by plastic strain gradients. In bending of thin beams and torsion of thin wires, mechanism-based strain gradient plasticity gives a significant increase in scaled bending moment and scaled torque due to strain gradient effects. For the growth of microvoids and cavitation instabilities, however, it is found that strain gradients have little effect on micron-sized voids, but submicron-sized voids can have a larger resistance against void growth. Finally, it is shown from the study of bimaterials in shear that the mesoscale cell size has little effect on global physical quantities (e.g. applied stresses), but may affect the local deformation field significantly.

Mechanism-based strain gradient plasticity— I. Theory

A mechanism-based theory of strain gradient plasticity (MSG) is proposed based on a multiscale framework linking the microscale notion of statistically stored and geometrically necessary dislocations to the mesoscale notion of plastic strain and strain gradient. This theory is motivated by our recent analysis of indentation experiments which strongly suggest a linear dependence of the square of plastic flow stress on strain gradient. While such linear dependence is predicted by the Taylor hardening model relating the flow stress to dislocation density, existing theories of strain gradient plasticity have failed to explain such behavior. We believe that a mesoscale theory of plasticity should not only be based on stress–strain behavior obtained from macroscopic mechanical tests, but should also draw information from micromechanical, gradient-dominant tests such as micro-indentation or nano-indentation. According to this viewpoint, we explore an alternative formulation of strain gradient plasticity in which the Taylor model is adopted as a founding principle. We distinguish the microscale at which dislocation interaction is considered from the mesoscale at which the plasticity theory is formulated. On the microscale, we assume that higher order stresses do not exist, that the square of flow stress increases linearly with the density of geometrically necessary dislocations, strictly following the Taylor model, and that the plastic flow retains the associative structure of conventional plasticity. On the mesoscale, the constitutive equations are constructed by averaging microscale plasticity laws over a representative cell. An expression for the effective strain gradient is obtained by considering models of geometrically necessary dislocations associated with bending, torsion and 2-D axisymmetric void growth. The new theory differs from all existing phenomenological theories in its mechanism-based guiding principles, although the mathematical structure is quite similar to the theory proposed by Fleck and Hutchinson. A detailed analysis of the new theory is presented in Part II of this paper.