Robustness analysis of a nucleic acid controller for a dynamic biomolecular process using the structured singular value

In the field of synthetic biology, theoretical frameworks and software tools are now available that allow control systems represented as chemical reaction networks to be translated directly into nucleic acid-based chemistry, and hence implement embedded control circuitry for biomolecular processes. However, the development of tools for analysing the robustness of such controllers is still in its infancy. An interesting feature of such control circuits is that, although the transfer function of a linear system can be easily implemented via a chemical network of catalysis, degradation and annihilation reactions, this introduces additional nonlinear dynamics, due to the annihilation kinetics. We exemplify this problem for a dynamical biomolecular feedback system, and demonstrate how the structured singular value (μ) analysis framework can be extended to rigorously analyse the robustness of this class of system. We show that parametric uncertainty in the system affects the location of its equilibrium, and that this must be taken into account in the analysis. We also show that the parameterisation of the system can be scaled for experimental feasibility without affecting its robustness properties, and that a statistical analysis via Monte Carlo simulation fails to uncover the worst-case uncertainty combination found by μ-analysis.</p

Sample size and power calculations for detecting changes in malaria transmission using antibody seroconversion rate.

BACKGROUND: Several studies have highlighted the use of serological data in detecting a reduction in malaria transmission intensity. These studies have typically used serology as an adjunct measure and no formal examination of sample size calculations for this approach has been conducted. METHODS: A sample size calculator is proposed for cross-sectional surveys using data simulation from a reverse catalytic model assuming a reduction in seroconversion rate (SCR) at a given change point before sampling. This calculator is based on logistic approximations for the underlying power curves to detect a reduction in SCR in relation to the hypothesis of a stable SCR for the same data. Sample sizes are illustrated for a hypothetical cross-sectional survey from an African population assuming a known or unknown change point. RESULTS: Overall, data simulation demonstrates that power is strongly affected by assuming a known or unknown change point. Small sample sizes are sufficient to detect strong reductions in SCR, but invariantly lead to poor precision of estimates for current SCR. In this situation, sample size is better determined by controlling the precision of SCR estimates. Conversely larger sample sizes are required for detecting more subtle reductions in malaria transmission but those invariantly increase precision whilst reducing putative estimation bias. CONCLUSIONS: The proposed sample size calculator, although based on data simulation, shows promise of being easily applicable to a range of populations and survey types. Since the change point is a major source of uncertainty, obtaining or assuming prior information about this parameter might reduce both the sample size and the chance of generating biased SCR estimates

A Step-up mu-Power Converter for Solar Energy Harvesting Applications, using Hill Climbing Maximum Power Point Tracking

This paper presents a step-up micro-power converter for solar energy harvesting applications. The circuit uses a SC voltage tripler architecture, controlled by an MPPT circuit based on the Hill Climbing algorithm. This circuit was designed in a 0.13 mu m CMOS technology in order to work with an a-Si PV cell. The circuit has a local power supply voltage, created using a scaled down SC voltage tripler, controlled by the same MPPT circuit, to make the circuit robust to load and illumination variations. The SC circuits use a combination of PMOS and NMOS transistors to reduce the occupied area. A charge re-use scheme is used to compensate the large parasitic capacitors associated to the MOS transistors. The simulation results show that the circuit can deliver a power of 1266 mu W to the load using 1712 mu W of power from the PV cell, corresponding to an efficiency as high as 73.91%. The simulations also show that the circuit is capable of starting up with only 19% of the maximum illumination level

Modelos de interacção genética de dois genes em fenótipos

Em trabalhos anteriores foram propostos diversos modelos estatísticos para a penetrância de forma a inferir a interacção de dois genes dial´elicos na construção de fenótipos binários complexos: modelos de acção independente, modelos de inibição e modelos de número mínimo de alelos. Estes modelos baseiam-se numa decomposição da penetrância através da abordagem por penetrâncias alélicas, que permitiu a inclusão dos conceitos mendelianos de dominância e recessividade alélica na sua modelação. Pretende-se aqui dar a conhecer os avanços mais recentes na parte da modelação da interacção genética, apresentando uma nova decomposição da penetrância e uma nova formulação matemática da dominância e da recessividade. Aplicam-se ainda ferramentas bayesianas para o ajustamento dos modelos de interacção genética a dados experimentais com recurso ao método de amostragem de Gibbs. Toda a metodologia é exemplificada num conjunto de dados de um estudo da susceptibilidade da malária cerebral em ratinhos

PID and state feedback controllers using DNA strand displacement reactions

Nucleic acid-based chemistry is a strong candidate framework for the construction of future synthetic biomolecular control circuits. Previous work has demonstrated the capacity of circuits based on DNA strand displacement (DSD) reactions to implement digital and analogue signal processing in vivo , including in mammalian cells. To date, however, feedback control system designs attempted within this framework have been restricted to extremely simple proportional or proportional-integral controller architectures. In this letter, we significantly extend the potential complexity of such controllers by showing how time-delays, numerical differentiation (to allow PID control), and state feedback may be implemented via chemical reaction network-based designs. Our controllers are implemented and tested using VisualDSD, a rapid-prototyping tool that allows precise analysis of computational devices implemented using nucleic acids, via both deterministic and stochastic simulations of the DSD reactions.11Nscopu

Physical Function and Quality of Life After Resection of Mobile Spine Chondrosarcoma.

Study Design:Retrospective cohort study. Objectives:(1) To assess patient-reported outcomes-physical function, pain, and quality of life-in patients who underwent resection of a mobile spine chondrosarcoma. (2) To assess complications (90 days), readmissions, reoperations, oncological outcomes, and neurologic status. Methods:Thirty-three patients with spinal conventional chondrosarcoma resection between 1984 and 2014 at one hospital were included. The primary outcome measures were-minimally 6 months after surgery-the EuroQol 5 Dimensions (EQ5D), PROMIS-Physical Function, PROMIS-Pain Intensity, and Oswestry (ODI) Disability Index, or Neck (NDI) Disability established in 14 out of 20 alive (70.0%) patients. Complications, readmission, reoperations, oncological outcomes, and neurological status were reported for the complete cohort of 33 patients. Results:After spine chondrosarcoma resection, patients (n = 14) reported worse physical function (median 43, range 22-61, P = .026), worse quality of life (median EQ5D 0.70, range 0.04-1, P = .022), and comparable pain intensity (median 47, range 31-56, P = .362) when compared with US general population values. The median NDI/ODI was 25 (range 0-72) indicating mild to moderate disability. Patients undergoing reoperation had worse patient-reported outcomes than those who did not. Eighteen (55.5%) out of 33 patients suffered complications (90 days), 14 (42.4%) had unplanned readmission, and 13 (39.4%) underwent reoperation. Intralesional resection was associated with increased readmission, reoperation, and recurrence rate. Conclusions:Chondrosarcoma affects quality of life and physical function and its treatment frequently results in complications and reoperations. Our findings can be used to inform future patients about expected outcomes

Generation of reconfigurable circuits from machine code

Tese de mestrado integrado. Engenharia Electrotécnica e de Computadores. Telecomunicações. Universidade do Porto. Faculdade de Engenharia. 201