Bottom-Up Construction of an Adaptive Enzymatic Reaction Network.

The reproduction of emergent behaviors in nature using reaction networks is an important objective in synthetic biology and systems chemistry. Herein, the first experimental realization of an enzymatic reaction network capable of an adaptive response is reported. The design is based on the dual activity of trypsin, which activates chymotrypsin while at the same time generating a fluorescent output from a fluorogenic substrate. Once activated, chymotrypsin counteracts the trypsin output by competing for the fluorogenic substrate and producing a non-fluorescent output. It is demonstrated that this network produces a transient fluorescent output under out-of-equilibrium conditions while the input signal persists. Importantly, in agreement with mathematical simulations, we show that optimization of the pulse-like response is an inherent trade-off between maximum amplitude and lowest residual fluorescence.

Preprogramming Complex Hydrogel Responses using Enzymatic Reaction Networks.

The creation of adaptive matter is heavily inspired by biological systems. However, it remains challenging to design complex material responses that are governed by reaction networks, which lie at the heart of cellular complexity. The main reason for this slow progress is the lack of a general strategy to integrate reaction networks with materials. Herein we use a systematic approach to preprogram the response of a hydrogel to a trigger, in this case the enzyme trypsin, which activates a reaction network embedded within the hydrogel. A full characterization of all the kinetic rate constants in the system enabled the construction of a computational model, which predicted different hydrogel responses depending on the input concentration of the trigger. The results of the simulation are in good agreement with experimental findings. Our methodology can be used to design new, adaptive materials of which the properties are governed by reaction networks of arbitrary complexity.

Moving towards Universal Health Coverage through the Development of Integrated Service Delivery Packages for Primary Health Care in the Solomon Islands.

The Solomon Islands Government is pursuing integrated care with the goal of improving the quality of health service delivery to rural populations. Under the auspices of Universal Health Coverage, integrated service delivery packages were developed which defined the clinical and public health services that should be provided at different levels of the health system. The process of developing integrated service delivery packages helped to identify key policy decisions the government needed to make in order to improve service quality and efficiency. The integrated service delivery packages have instigated the revision of job descriptions and are feeding into the development of a human resource plan for health. They are also being used to guide infrastructure development and health system planning and should lead to better management of resources. The integrated service delivery packages have become a key tool to operationalise the government's policy to move towards a more efficient, equitable, quality and sustainable health system.

Ambulance services as part of the district health system in low-income countries: a feasibility study from Cambodia.

BACKGROUND: Emergency referral care is considered an essential component of the district health system. Nevertheless, the establishment of effective and durable transport arrangements of such referral care by use of an ambulance is considered controversial in low-income countries. OBJECTIVE: We aim to assess the extent to which an ambulance service as part of the district health system is feasible in rural Cambodia. METHODS: In a rural health district, we assessed the population's perception of the ambulance service, its recurrent costs requirements, government financial contribution to its operations, profile and medical conditions of ambulance (non)users, reasons for (non)use of the ambulance and contextual factors required for the ambulance services to operate. This observation was obtained through nine key informant interviews, five focus group discussions, structured interviews with 225 caretakers of admitted patients, a 1-month census of admitted emergency cases and assessment of annual recurrent costs for the ambulance services. RESULTS: The ambulance services were well received by the population and authorities and appeared to reinforce an appreciation of the hospital. Ambulance services were mainly used by the poor and by women, especially for emergency obstetric care. Less than half the number of transported patients, 44%, was considered a medical emergency. The direct cost to the hospital per collected emergency case was $34.4. CONCLUSION: When certain conditions are met, effective ambulance services can be an integral part of the district health system and positively contribute to the population's appreciation of the hospital services and respective district health system. Copyright © 2015 John Wiley & Sons, Ltd.

Influence of molecular structure on the properties of out-of-equilibrium oscillating enzymatic reaction networks.

Our knowledge of the properties and dynamics of complex molecular reaction networks, for example those found in living systems, considerably lags behind the understanding of elementary chemical reactions. In part, this is because chemical reactions networks are nonlinear systems that operate under conditions far from equilibrium. Of particular interest is the role of individual reaction rates on the stability of the network output. In this research we use a rational approach combined with computational methods, to produce complex behavior (in our case oscillations) and show that small changes in molecular structure are sufficient to impart large changes in network behavior.

Rational design of functional and tunable oscillating enzymatic networks.

Life is sustained by complex systems operating far from equilibrium and consisting of a multitude of enzymatic reaction networks. The operating principles of biology's regulatory networks are known, but the in vitro assembly of out-of-equilibrium enzymatic reaction networks has proved challenging, limiting the development of synthetic systems showing autonomous behaviour. Here, we present a strategy for the rational design of programmable functional reaction networks that exhibit dynamic behaviour. We demonstrate that a network built around autoactivation and delayed negative feedback of the enzyme trypsin is capable of producing sustained oscillating concentrations of active trypsin for over 65 h. Other functions, such as amplification, analog-to-digital conversion and periodic control over equilibrium systems, are obtained by linking multiple network modules in microfluidic flow reactors. The methodology developed here provides a general framework to construct dissipative, tunable and robust (bio)chemical reaction networks.

THE IMPORTANCE OF MONITORING DOMESTIC PUBLIC HEALTH LAW AND LEGAL SYSTEMS SUPPORTING GLOBAL HEALTH GOVERNANCE: DEVELOPMENT OF AN ANALYTICAL FRAMEWORK TO ASSESS THE DOMESTIC PUBLIC HEALTH LAW SITUATION IN THE WESTERN PACIFIC REGION COUNTRIES.

The aims of this study are to present an argument that emphasizes the usefulness of an analysis framework for analyzing public health law and legal systems; identifying methods for improving the application of this framework, including its academic value for public health law; and enhancing the future use of the framework for supporting global health governance. To help formulate the initial analysis framework and tool, we have, along with expert consultations, conducted a literature review on global health governance and public health law. Meetings were also held with World Health Organization (WHO) Western Pacific Regional Office (WPRO) technical staff members on the applicability and benefits of the framework and tool. Monitoring public health laws and legal systems of countries can be used to understand governance and improve people's health.

Fluorescent hydrogels for studying Ca(2+)-dependent reaction-diffusion processes.

Here, we report a convenient experimental platform to study the diffusion of Ca(2+) in the presence of a Ca(2+)-binding protein (Calbindin D28k). This work opens up new possibilities to elucidate the physical chemistry of complex Ca(2+)-dependent reaction-diffusion networks that are abundant in living cells.