A Kernel for Open Source Drug Discovery in Tropical Diseases

Open source drug discovery, a promising alternative avenue to conventional patent-based drug development, has so far remained elusive with few exceptions. A major stumbling block has been the absence of a critical mass of preexisting work that volunteers can improve through a series of granular contributions. This paper introduces the results from a newly assembled computational pipeline for identifying protein targets for drug discovery in ten organisms that cause tropical diseases. We have also experimentally tested two promising targets for their binding to commercially available drugs, validating one and invalidating the other. The resulting kernel provides a base of drug targets and lead candidates around which an open source community can nucleate. We invite readers to donate their judgment and in silico and in vitro experiments to develop these targets to the point where drug optimization can begin

Open-system orchestration as a relational source of sensing capabilities: Evidence from a venture association

Research on innovation networks has highlighted the pivotal role that actors with more prominence and power, such as hub firms, may play in orchestrating the activities of other network members along a collective innovation effort. Our study examined the undertheorized, but no less important, type of orchestration that characterizes other organizations, such as business incubators and venture associations, who seek to support the dispersed entrepreneurial efforts of network members. We refer to this type as ‘open-system’ orchestration, as opposed to the commonly studied ‘closed-system’ type performed by hub firms. Our findings reveal how the processes of open-system orchestration differ markedly from those of closed-system orchestration, and detail how these processes influence the micro-foundations of network members’ sensing capabilities. By doing so, we also offer empirical substantiation and theoretical elaboration to the idea that dynamic capabilities might not reside exclusively inside firms, but could be co-created relationally with other parties in the business ecosystem

Corporate governance and national institutions: A review and emerging research agenda

We present a critique of corporate governance research grounded in agency theory and propose that cross-national comparison of corporate governance should consider how the nature and extent of agency relationships differ across different institutional contexts. Building on prior governance studies grounded in sociology and organizational theory we argue that performance outcomes of boards of directors, ownership concentration, and executive incentives may differ depending on the legal system and institutional characteristics in a specific country. Institutions may also affect the extent of complimentarity/substitution among different firm-level governance practices producing patterned variations in firm-level governance mechanisms. Our discussion suggests that researchers need to develop more holistic, institutionally embedded governance framework to analyze organizational outcomes of various governance practices

Business angel exits: A theory of planned behaviour perspective

Although there are a handful of studies on business angel investment returns, the business angel literature has given little or no attention to exits and the exit strategy. This is surprising given that a primary objective of investing is to achieve a capital gain through some form of liquidity event. Using the theory of planned behaviour (TPB) as an interpretative heuristic, we examine how exits happen: specifically, what are the motivations to seek an exit and to what extent are they planned or opportunistic? Based on multiple case studies in which business angels were invited to tell the story of their most recent exit(s), the evidence suggests that the majority of liquidity events are the outcome of planned behaviour. We propose a typology of angel-backed investment exits as the basis for identifying future directions for research and developing practical advice to angels on effective business practices

Proteins with Complex Architecture as Potential Targets for Drug Design: A Case Study of Mycobacterium tuberculosis

Lengthy co-evolution of Homo sapiens and Mycobacterium tuberculosis, the main causative agent of tuberculosis, resulted in a dramatically successful pathogen species that presents considerable challenge for modern medicine. The continuous and ever increasing appearance of multi-drug resistant mycobacteria necessitates the identification of novel drug targets and drugs with new mechanisms of action. However, further insights are needed to establish automated protocols for target selection based on the available complete genome sequences. In the present study, we perform complete proteome level comparisons between M. tuberculosis, mycobacteria, other prokaryotes and available eukaryotes based on protein domains, local sequence similarities and protein disorder. We show that the enrichment of certain domains in the genome can indicate an important function specific to M. tuberculosis. We identified two families, termed pkn and PE/PPE that stand out in this respect. The common property of these two protein families is a complex domain organization that combines species-specific regions, commonly occurring domains and disordered segments. Besides highlighting promising novel drug target candidates in M. tuberculosis, the presented analysis can also be viewed as a general protocol to identify proteins involved in species-specific functions in a given organism. We conclude that target selection protocols should be extended to include proteins with complex domain architectures instead of focusing on sequentially unique and essential proteins only

A dynamic theory of network failure

Organizational and sociological research dealing with network governance has mainly focused on network advantages rather than on their problems or dysfunctionalities. This left partially unexplored the field of network failure. Even if some early attempts at explicitly theorizing network failures have been made, we argue that explanations based mainly on social conditions (ignorance and opportunism) offered by this emerging theory (e.g. Schrank and Whitford, 2011), are not exhaustive. In this article we report the results of our empirical investigation on the underperforming network between the worldwide famous Venice Film Festival and its local hospitality system (in Venice, Italy). In the case study we are presenting, we will show how institutions have not been able to inhibit opportunism and sustain trust among network members because of mobilizing practices developed across formal lines of communication. With this work we propose a dynamic theory of network failure, answering to the more general call for network theories to focus the attention on agency and micro-processes