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This exploratory study takes a look at the puzzle of what type of contracts are suitable for governing innovation, with particular atte ntion to inter-firm networks. It employs a conceptual framework that integrates organizational theory of formal coordination with economic perspectives on contracting, and innovate previous analyses in two ways: developing an assessment of alternative contractual forms in terms of knowledge governance and not only in terms of conflict resolution; analyzing contracts according to the intensity at which they incorporate not only market-like mechanisms, but also hierarchical and bureaucratic mechanisms, and a usually neglected array of associational and democratic mechanisms, as related to the level of uncertainty and innovation. A new type of 'associational' and 'constitutional' contract, resource based rather than action-based, is singled out as particularly fit to the governance of innovation. The framework is empirically applied to content analyze the written agreements regulating inter firm alliances for innovation in a comparative case study approach

Types of Complementarity, Combinative Organization Forms and Structural Heterogeneity: Beyond Discrete Structural Alternatives

In the first Section, this paper offer a critical re-reading of the notions of organization forms as clusters of 'attributes' in organization theory and organization economics aimed at singling out what they have established and what problems have to be solved. In the second Section, building on those elements and on earlier works of the authors, the paper provides a typology of organizational ‘features’, a theory of how they are expected to combine inspired by an analogy with chemistry, and a formalized operationalization of the main propositions through an innovative application of Boolean algebra

The co-design of contractual and extra-contractual governance: lessons from the project-based economy

Organizational economics tends to express a pessimistic view on the effectiveness of inter-firm contracts under uncertainty, and sees the use of authority and of relational governance as possible remedies. Organization theory inspires some skepticism on the effectiveness of these therapies. In particular, it identifies also reasons to expect a sustained level of formalization in strategic alliances and, conversely, to expect a moderate use of centralization. To help filling this gap, this study empirically assesses the relationship between uncertainty and complexity in the context of strategic alliances, and the use of formalization and centralization for their governance. The assessment extends to the intensity of use and the relationships of three modes of governance: contractual, formal extra-contractual, and informal and social. This exercise is carried out on a new database that collects in formation on 540 project-based alliances. We find that inter-organizational projects employ a mix of contractual and extra-contractual governance mechanisms. Different from usual conceptualization, these agreements are not characterized by high informality. Extra contractual governance seems to be employed to respond to additional factors, rather than to substitute or complement formal agreements. Finally, the pattern of allocation of property rights also interestingly deviates from standard property right theory predictions, to conform to a more pluralist, negotiation based view

The bearable lightness of inter-firm strategic alliances: resource-based and procedural contracting

This paper inquires into how contracts can regulate the complex and uncertain matters on which strategic alliances get formed. It highlights that contracts can be 'light' without being mistakenly incomplete. It is argued that the contracts constituting and regulating strategic alliances are composed by an associational core, focused on resource commitments and on the specification of property rights, broadly intended; and of a belt of contractual clauses incorporating a variety of coordination mechanisms (including, and actually privileging, joint decision making procedures). The interpretive power of the framework is illustrated through the analys is of three alliance contracts

Configurational Analysis and Organization Design: Towards a Theory of Structural Heterogeneity

This chapter reconstructs the roots, evolution and some prospects of configurational analysis (CA) in organization theory (OT) and organizational economics (OE), focusing on those components of CA that are particularly relevant to organizational design. This excursus leads to: a) revealing the presence of elements of CA in many OT and OE approaches - a continuity that is seldom acknowledged and arguably extends (rather than diminishes) the implications and applications of CA; b) identifying ‘structural heterogeneity’ (SH) -both ‘internal’ among organizational attributes within a configuration, and ‘external’ among configurations under the same conditions (or ‘equifinality’)- as an organizational property that can be distinctively studied by CA. This claim, as well as the substantive insights that can be gained by a configurational analysis of structural heterogeneity, is substantiated by an empirical analysis on a multi-sector sample of firm

c-Myc Accelerates S-Phase and Requires WRN to Avoid Replication Stress

c-Myc interacts with components of the pre-replication complex and directly regulates DNA replication [1]. However the consequences of this novel c-Myc function on cell cycle dynamics and replication-associated damage are unknown. Here, we show that c-Myc overexpression in primary human fibroblasts markedly accelerates S-phase while c-Myc deficient fibroblasts exhibit a prolonged S-phase. We also show that the Werner DNA helicase protein (WRN) plays a critical role in supporting c-Myc-driven S-phase, as depletion of WRN in c-Myc overexpressing cells increases DNA damage specifically at sites of DNA synthesis. This excess DNA damage activates a “replication stress” pathway involving ATR, CHK1, CHK2, and p53, leading to rapid senescence of WRN deficient c-Myc overexpressing cells. Indeed, depletion of p53 rescues this senescence response. We propose that WRN functions to repair abnormal replication structures caused by the acceleration of DNA replication by c-Myc. This work provides an additional mechanistic explanation for c-Myc-induced DNA damage and senescence, and reveals a vulnerability of c-Myc overexpressing cells that could potentially be exploited in cancer therapy

Depicting conformational ensembles of \u3b1-synuclein by single molecule force spectroscopy and native mass spectroscopy

Description of heterogeneous molecular ensembles, such as intrinsically disordered proteins, represents a challenge in structural biology and an urgent question posed by biochemistry to interpret many physiologically important, regulatory mechanisms. Single-molecule techniques can provide a unique contribution to this field. This work applies single molecule force spectroscopy to probe conformational properties of \u3b1-synuclein in solution and its conformational changes induced by ligand binding. The goal is to compare data from such an approach with those obtained by native mass spectrometry. These two orthogonal, biophysical methods are found to deliver a complex picture, in which monomeric \u3b1-synuclein in solution spontaneously populates compact and partially compacted states, which are differently stabilized by binding to aggregation inhibitors, such as dopamine and epigallocatechin-3-gallate. Analyses by circular dichroism and Fourier-transform infrared spectroscopy show that these transitions do not involve formation of secondary structure. This comparative analysis provides support to structural interpretation of charge-state distributions obtained by native mass spectrometry and helps, in turn, defining the conformational components detected by single molecule force spectroscopy

A Cognitive Mapping Approach to Business Models: Representing Causal Structures and Mechanisms

Research has highlighted the cognitive nature of the business model intended as a cognitive representation describing a business’ value creation and value capture activities. Whereas the content of the business model has been extensively investigated from this perspective, less attention has been paid to the business model’s causal structure – i.e. the pattern of causeeffect relations that, in top managers’ or entrepreneurs’ understandings, link value creation and value capture activities. Building on the strategic cognition literature, this paper argues that conceptualizing and analyzing business models as cognitive maps can shed light on four important properties of a business model’s causal structure: the levels of complexity, focus, and clustering that characterize the causal structure; and the mechanisms underlying the causal links featured in that structure. I use examples of business models drawn from the literature as illustrations to describe these four properties. Finally, I discuss the value of a cognitive mapping approach for augmenting extant theories and practices of business model design

Exploring the topology of the plausible: Fs/QCA counterfactual analysis and the plausible fit of unobserved organizational configurations

The main aim of this contribution is to expand the dominant rationale of organizational design research by including solutions and possibilities not observed in reality. We believe that the counterfactual approach to configurations responds to an open call in organization theory and strategy to move the modelling of fit towards a more robust and theory-based specification. With this new approach we propose to rediscover the roots of organization design as a distinct normative discipline that ‘should stand approximately in relation to the basic social sciences as engineering stands with respect to physical sciences or medicine to the biological’. At a more general level, our view implies an expansion of the dominant meaning of the concept of ‘relevance’ in management research. While we agree with Gulati (2007: 780) that we as scholars should probe ‘more deeply into the problems and other issues that managers care about’, we also believe that relevance does not necessarily mean that researchers have to use an ex-post rationality by studying only empirically frequent phenomena. In contrast, we think that any management esearcher should bring with her or himself a fragment of the spirit of the great Greek philosopher Anaximander (c. 610–c. 546 BC), who foresaw the concept of the infinite universe without the support of any empirical observation and against the predominant wisdom of the time. Not by chance, Karl Popper (1998) onsidered Anaximander’s intuitions among the most vivid demonstrations of the power of human thought and logic

Embelin binds to human neuroserpin and impairs its polymerisation

Neuroserpin (NS) is a serpin inhibitor of tissue plasminogen activator (tPA) in the brain. The polymerisation of NS pathologic mutants is responsible for a genetic dementia known as familial encephalopathy with neuroserpin inclusion bodies (FENIB). So far, a pharmacological treatment of FENIB, i.e. an inhibitor of NS polymerisation, remains an unmet challenge. Here, we present a biophysical characterisation of the effects caused by embelin (EMB a small natural compound) on NS conformers and NS polymerisation. EMB destabilises all known NS conformers, specifically binding to NS molecules with a 1:1 NS:EMB molar ratio without unfolding the NS fold. In particular, NS polymers disaggregate in the presence of EMB, and their formation is prevented. The NS/EMB complex does not inhibit tPA proteolytic activity. Both effects are pharmacologically relevant: firstly by inhibiting the NS polymerisation associated to FENIB, and secondly by potentially antagonizing metastatic processes facilitated by NS activity in the brain