Comprehensive characterization of molecular interactions based on nanomechanics

Molecular interaction is a key concept in our understanding of the biological mechanisms of life. Two physical properties change when one molecular partner binds to another. Firstly, the masses combine and secondly, the structure of at least one binding partner is altered, mechanically transducing the binding into subsequent biological reactions. Here we present a nanomechanical micro-array technique for bio-medical research, which not only monitors the binding of effector molecules to their target but also the subsequent effect on a biological system in vitro. This label-free and real-time method directly and simultaneously tracks mass and nanomechanical changes at the sensor interface using micro-cantilever technology. To prove the concept we measured lipid vesicle (approximately 748*10(6) Da) adsorption on the sensor interface followed by subsequent binding of the bee venom peptide melittin (2840 Da) to the vesicles. The results show the high dynamic range of the instrument and that measuring the mass and structural changes simultaneously allow a comprehensive discussion of molecular interactions

Psychological resilience of entrepreneurs: A review and agenda for future research

Given that entrepreneurs face substantial adversity in initiating and developing new ventures, a burgeoning stream of research has sought to understand the concept of entrepreneurs’ psychological resilience. To structure and synthesize what we know about entrepreneurs’ psychological resilience, we systematically review the empirical literature to provide insights on how it has been conceptualized and operationalized, along with its key antecedents and outcomes. Based on our review, we advance a promising agenda for future research, grounded in connecting the psychological resilience of entrepreneurs to other research areas connected to the new venture development process. Overall, we point to the urgent need for theoretical precision to enhance the utility of empirical contributions, suggest promising research designs, expand on the important role of adversity, discuss potential boundary conditions, elaborate on the link between entrepreneurs’ psychological resilience and organizational resilience, and address the potential dark side of resilience

Absorbing customer knowledge: how customer involvement enables service design success

Customers are a knowledge resource outside of the firm that can be utilized for new service success by involving them in the design process. However, existing research on the impact of customer involvement (CI) is inconclusive. Knowledge about customers’ needs and on how best to serve these needs (articulated in the service concept) is best obtained from customers themselves. However, codesign runs the risk of losing control of the service concept. This research argues that of the processes of external knowledge, acquisition (via CI), customer knowledge assimilation, and concept transformation form a capability that enables the firm to exploit customer knowledge in the form of a successful new service. Data from a survey of 126 new service projects show that the impact of CI on new service success is fully mediated by customer knowledge assimilation (the deep understanding of customers’ latent needs) and concept transformation (the modification of the service concept due to customer insights). However, its impact is more nuanced. CI exhibits an “∩”-shaped relationship with transformation, indicating there is a limit to the beneficial effect of CI. Its relationship with assimilation is “U” shaped, suggesting a problem with cognitive inertia where initial learnings are ignored. Customer knowledge assimilation directly impacts success, while concept transformation only helps success in the presence of resource slack. An evolving new service design is only beneficial if the firm has the flexibility to adapt to change

Predictive Task Monitoring for Business Processes

Information sources providing real-time status of physical objects have drastically increased in recent times. So far, research in business process monitoring has mainly focused on checking the completion of tasks. However, the availability of real-time information allows for a more detailed tracking of individual business tasks. This paper describes a framework for controlling the safe execution of tasks and signalling possible misbehaviours at runtime. It outlines a real use case on smart logistics and the preliminary results of its application.European Union FP7/2007-2013 / 318275 (GET Service

Nanomechanical detection of antibiotic-mucopeptide binding in a model for superbug drug resistance

The alarming growth of the antibiotic-resistant superbugs methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) is driving the development of new technologies to investigate antibiotics and their modes of action. We report the label-free detection of vancomycin binding to bacterial cell wall precursor analogues (mucopeptides) on cantilever arrays, with 10 nM sensitivity and at clinically relevant concentrations in blood serum. Differential measurements quantified binding constants for vancomycin-sensitive and vancomycin-resistant mucopeptide analogues. Moreover, by systematically modifying the mucopeptide density we gain new insights into the origin of surface stress. We propose that stress is a product of a local chemical binding factor and a geometrical factor describing the mechanical connectivity of regions affected by local binding in terms of a percolation process. Our findings place BioMEMS devices in a new class of percolative systems. The percolation concept will underpin the design of devices and coatings to significantly lower the drug detection limit and may also impact on our understanding of antibiotic drug action in bacteria.Comment: Comments: This paper consists of the main article (6 pages, 5 figures) plus Supplemental Material (6 pages, 3 figures). More details are available at http://www.london-nano.co

I Tensed the Laws and the Laws Won: Non-Eternalist Humeanism

ABSTRACT In this paper, I propose a variant of a Humean account of laws called "Open Future Humeanism" (OFH), which holds that since the laws supervene partly on future events, there are at any instant infinitely many possible future courses of events. I argue that if one wants to take the openness of the future that OFH proposes ontologically serious, then OFH is best represented within a growing block view of time. I further discuss some of OFH's problems which stem from the fact that in this view, there are no laws as long as time progresses. These problems can be solved by adding a temporal operator to the laws, so that at any instant, we get a set of tensed laws which held up to and including that instant

An online machine learning framework for early detection of product failures in an Industry 4.0 context

Current paradigms such as the Internet of Things (IoT) and cyber-physical systems are transforming production environments, where related processes are not only faster and with higher standards, but also more flexible and adaptable to changes in the environment. To address the ever-increasing flexibility requirements while keeping current production standards, a new set of technologies is needed. This paper presents an IoT machine learning and orchestration framework, applied to detection of failures of surface mount devices during production. The paper shows how to build a scalable and flexible system for real-time, online machine learning. Furthermore, the approach is evaluated by using a novel and realistic simulation of a production line for electronic devices as a case study. The system evaluation is done in a holistic manner by analyzing various aspects involving the software architecture, computational scalability, model accuracy, production performance, among others