Can Wolbachia be used to control malaria?

Malaria is a mosquito-borne infectious disease caused by Plasmodium parasites transmitted by the infectious bite of Anopheles mosquitoes. Vector control of malaria has predominantly focused on targeting the adult mosquito through insecticides and bed nets. However, current vector control methods are often not sustainable for long periods so alternative methods are needed. A novel biocontrol approach for mosquito-borne diseases has recently been proposed, it uses maternally inherited endosymbiotic Wolbachia bacteria transinfected into mosquitoes in order to interfere with pathogen transmission. Transinfected Wolbachia strains in Aedes aegypti mosquitoes, the primary vector of dengue fever, directly inhibit pathogen replication, including Plasmodium gallinaceum, and also affect mosquito reproduction to allow Wolbachia to spread through mosquito populations. In addition, transient Wolbachia infections in Anopheles gambiae significantly reduce Plasmodium levels. Here we review the prospects of using a Wolbachia-based approach to reduce human malaria transmission through transinfection of Anopheles mosquitoes.

New structures for goat corrals to control peridomestic populations of Triatoma infestans (Hemiptera: Reduviidae) in the Gran Chaco of Argentina

Goat production is an important economic activity for rural communities in the Gran Chaco of Argentina. Goat corrals are important for the survival of peridomestic populations of Triatoma infestans. This study evaluated the impact of modifying the traditional structure of goat corrals on T. infestans populations and goat productivity in the region of Los Llanos (La Rioja). Thirty-nine experimental corrals were constructed and 57 traditional corrals were used as controls. We evaluated the infestations of the control and experimental corrals for five years following construction of the structures. The results showed that the new structures did not prevent the colonization, although it enhanced the detection of infestation at low densities of T. infestans. No significant difference was found in T. infestans population abundance between control and experimental corrals, probably because of the different detectability in the two types of structures, especially among the small nymphs. Although goat productivity average was higher in experimental than in control corrals, no significant difference was found because of high variability. The new structures can be used as a complement to promote the development of rural communities. Acceptability and adoption of the new corrals by the owners was high, as the enclosures offered better protection for the goats, increased growth of kids and facilitated herd handling.

Novel polymerase chain reaction-restriction fragment length polymorphism assay to determine internal transcribed spacer-2 group in the Chagas disease vector, Triatoma dimidiata (Latreille, 1811)

Triatoma dimidiata is the most important Chagas disease insect vector in Central America as this species is primarily responsible for Trypanosoma cruzi transmission to humans, the protozoan parasite that causes Chagas disease. T. dimidiata sensu lato is a genetically diverse assemblage of taxa and effective vector control requires a clear understanding of the geographic distribution and epidemiological importance of its taxa. The nuclear ribosomal internal transcribed spacer 2 (ITS-2) is frequently used to infer the systematics of triatomines. However, oftentimes amplification and sequencing of ITS-2 fails, likely due to both the large polymerase chain reaction (PCR) product and polymerase slippage near the 5' end. To overcome these challenges we have designed new primers that amplify only the 3'-most 200 base pairs of ITS-2. This region distinguishes the ITS-2 group for 100% of known T. dimidiata haplotypes. Furthermore, we have developed a PCR-restriction fragment length polymorphism (RFLP) approach to determine the ITS-2 group, greatly reducing, but not eliminating, the number of amplified products that need to be sequenced. Although there are limitations with this new PCR-RFLP approach, its use will help with understanding the geographic distribution of T. dimidiata taxa and can facilitate other studies characterising the taxa, e.g. their ecology, evolution and epidemiological importance, thus improving vector control.

Interruption of vector transmission by native vectors and “the art of the possible”

In a recent article in the Reader’s Opinion, advantages and disadvantages of the certification processes of interrupted Chagas disease transmission (American trypanosomiasis) by native vector were discussed. Such concept, accepted by those authors for the case of endemic situations with introduced vectors, has been built on a long and laborious process by endemic countries and Subregional Initiatives for Prevention, Control and Treatment of Chagas, with Technical Secretariat of the Pan American Health Organization/World Health Organization, to create a horizon target and goal to concentrate priorities and resource allocation and actions. With varying degrees of sucess, which are not replaceable for a certificate of good practice, has allowed during 23 years to safeguard the effective control of transmission of Trypanosoma cruzi not to hundreds of thousands, but millions of people at risk conditions, truly “the art of the possible.”

Acute Chagas disease in El Salvador 2000-2012 - Need for surveillance and control

Several parasitological studies carried out in El Salvador between 2000-2012 showed a higher frequency of acute cases of Chagas disease than that in other Central American countries. There is an urgent need for improved Chagas disease surveillance and vector control programs in the provinces where acute Chagas disease occurs and throughout El Salvador as a whole.

Where do these bugs come from? Phenotypic structure ofTriatoma infestans populations after control interventions in the Argentine Chaco

House re-invasion by native triatomines after insecticide-based control campaigns represents a major threat for Chagas disease vector control. We conducted a longitudinal intervention study in a rural section (Area III, 407 houses) of Pampa del Indio, northeastern Argentina, and used wing geometric morphometry to compare pre-spray and post-spray (re-infestant bugs) Triatoma infestanspopulations. The community-wide spraying with pyrethroids reduced the prevalence of house infestation by T. infestans from 31.9% to < 1% during a four-year follow-up, unlike our previous studies in the neighbouring Area I. Two groups of bug collection sites differing in wing shape variables before interventions (including 221 adults from 11 domiciles) were used as a reference for assigning 44 post-spray adults. Wing shape variables from post-spray, high-density bug colonies and pre-spray groups were significantly different, suggesting that re-infestant insects had an external origin. Insects from one house differed strongly in wing shape variables from all other specimens. A further comparison between insects from both areas supported the existence of independent re-infestation processes within the same district. These results point to local heterogeneities in house re-infestation dynamics and emphasise the need to expand the geographic coverage of vector surveillance and control operations to the affected region.

Feedback control of unstable cellular solidification fronts

We present a feedback control scheme to stabilize unstable cellular patterns during the directional solidification of a binary alloy. The scheme is based on local heating of cell tips which protrude ahead of the mean position of all tips in the array. The feasibility of this scheme is demonstrated using phase-field simulations and, experimentally, using a real-time image processing algorithm, to track cell tips, coupled with a movable laser spot array device to heat the tips locally. We demonstrate, both numerically and experimentally, that spacings well below the threshold for a period-doubling instability can be stabilized. As predicted by the numerical calculations, cellular arrays become stable with uniform spacing through the feedback control which is maintained with minimal heating.

A Gain Scheduling Model Predictive Controller for Blood Glucose Control in Type 1 Diabetes

This paper presents a control strategy for blood glucose(BG) level regulation in type 1 diabetic patients. To design the controller, model-based predictive control scheme has been applied to a newly developed diabetic patient model. The controller is provided with a feedforward loop to improve meal compensation, a gain-scheduling scheme to account for different BG levels, and an asymmetric cost function to reduce hypoglycemic risk. A simulation environment that has been approved for testing of artificial pancreas control algorithms has been used to test thecontroller. The simulation results show a good controller performance in fasting conditions and meal disturbance rejection, and robustness against model–patient mismatch and errors in mealestimation

Phase voltage control and filtering in a converter-fed single-phase customer-end system of the LVDC distribution network

In recent years, the network vulnerability to natural hazards has been noticed. Moreover, operating on the limits of the network transmission capabilities have resulted in major outages during the past decade. One of the reasons for operating on these limits is that the network has become outdated. Therefore, new technical solutions are studied that could provide more reliable and more energy efficient power distributionand also a better profitability for the network owner. It is the development and price of power electronics that have made the DC distribution an attractive alternative again. In this doctoral thesis, one type of a low-voltage DC distribution system is investigated. Morespecifically, it is studied which current technological solutions, used at the customer-end, could provide better power quality for the customer when compared with the current system. To study the effect of a DC network on the customer-end power quality, a bipolar DC network model is derived. The model can also be used to identify the supply parameters when the V/kW ratio is approximately known. Although the model provides knowledge of the average behavior, it is shown that the instantaneous DC voltage ripple should be limited. The guidelines to choose an appropriate capacitance value for the capacitor located at the input DC terminals of the customer-end are given. Also the structure of the customer-end is considered. A comparison between the most common solutions is made based on their cost, energy efficiency, and reliability. In the comparison, special attention is paid to the passive filtering solutions since the filter is considered a crucial element when the lifetime expenses are determined. It is found out that the filter topology most commonly used today, namely the LC filter, does not provide economical advantage over the hybrid filter structure. Finally, some of the typical control system solutions are introduced and their shortcomings are presented. As a solution to the customer-end voltage regulation problem, an observer-based control scheme is proposed. It is shown how different control system structures affect the performance. The performance meeting the requirements is achieved by using only one output measurement, when operating in a rigid network. Similar performance can be achieved in a weak grid by DC voltage measurement. An additional improvement can be achieved when an adaptive gain scheduling-based control is introduced. As a conclusion, the final power quality is determined by a sum of various factors, and the thesis provides the guidelines for designing the system that improves the power quality experienced by the customer.

Analysis and Control of Excitation, Field Weakening and Stability in Direct Torque Controlled Electrically Excited Synchronous Motor Drives

Direct torque control (DTC) is a new control method for rotating field electrical machines. DTC controls directly the motor stator flux linkage with the stator voltage, and no stator current controllers are used. With the DTC method very good torque dynamics can be achieved. Until now, DTC has been applied to asynchronous motor drives. The purpose of this work is to analyse the applicability of DTC to electrically excited synchronous motor drives. Compared with asynchronous motor drives, electrically excited synchronous motor drives require an additional control for the rotor field current. The field current control is called excitation control in this study. The dependence of the static and dynamic performance of DTC synchronous motor drives on the excitation control has been analysed and a straightforward excitation control method has been developed and tested. In the field weakening range the stator flux linkage modulus must be reduced in order to keep the electro motive force of the synchronous motor smaller than the stator voltage and in order to maintain a sufficient voltage reserve. The dynamic performance of the DTC synchronous motor drive depends on the stator flux linkage modulus. Another important factor for the dynamic performance in the field weakening range is the excitation control. The field weakening analysis considers both dependencies. A modified excitation control method, which maximises the dynamic performance in the field weakening range, has been developed. In synchronous motor drives the load angle must be kept in a stabile working area in order to avoid loss of synchronism. The traditional vector control methods allow to adjust the load angle of the synchronous motor directly by the stator current control. In the DTC synchronous motor drive the load angle is not a directly controllable variable, but it is formed freely according to the motor’s electromagnetic state and load. The load angle can be limited indirectly by limiting the torque reference. This method is however parameter sensitive and requires a safety margin between the theoretical torque maximum and the actual torque limit. The DTC modulation principle allows however a direct load angle adjustment without any current control. In this work a direct load angle control method has been developed. The method keeps the drive stabile and allows the maximal utilisation of the drive without a safety margin in the torque limitation.

Novel force control methods in a teleoperation system of a hydraulic slider

The objective of the this research project is to develop a novel force control scheme for the teleoperation of a hydraulically driven manipulator, and to implement an ideal transparent mapping between human and machine interaction, and machine and task environment interaction. This master‘s thesis provides a preparatory study for the present research project. The research is limited into a single degree of freedom hydraulic slider with 6-DOF Phantom haptic device. The key contribution of the thesis is to set up the experimental rig including electromechanical haptic device, hydraulic servo and 6-DOF force sensor. The slider is firstly tested as a position servo by using previously developed intelligent switching control algorithm. Subsequently the teleoperated system is set up and the preliminary experiments are carried out. In addition to development of the single DOF experimental set up, methods such as passivity control in teleoperation are reviewed. The thesis also contains review of modeling of the servo slider in particular reference to the servo valve. Markov Chain Monte Carlo method is utilized in developing the robustness of the model in presence of noise.

Design and Control of Permanent Magnet Synchronous Machine for Hybrid Electric Vehicle

This master’s thesis mainly focuses on the design requirements of an Electric drive for Hybrid car application and its control strategy to achieve a wide speed range. It also emphasises how the control and performance requirements are transformed into its design variables. A parallel hybrid topology is considered where an IC engine and an electric drive share a common crank shaft. A permanent magnet synchronous machine (PMSM) is used as an electric drive machine. Performance requirements are converted into Machine design variables using the vector model of PMSM. Main dimensions of the machine are arrived using analytical approach and Finite Element Analysis (FEA) is used to verify the design and performance. Vector control algorithm was used to control the machine. The control algorithm was tested in a low power PMSM using an embedded controller. A prototype of 10 kW PMSM was built according to the design values. The prototype was tested in the laboratory using a high power converter. Tests were carried out to verify different operating modes. The results were in agreement with the calculations.

Accuracy Analysis of Frequency Converter Estimates in Diagnostic Applications

Transportation of fluids is one of the most common and energy intensive processes in the industrial and HVAC sectors. Pumping systems are frequently subject to engineering malpractice when dimensioned, which can lead to poor operational efficiency. Moreover, pump monitoring requires dedicated measuring equipment, which imply costly investments. Inefficient pump operation and improper maintenance can increase energy costs substantially and even lead to pump failure. A centrifugal pump is commonly driven by an induction motor. Driving the induction motor with a frequency converter can diminish energy consumption in pump drives and provide better control of a process. In addition, induction machine signals can also be estimated by modern frequency converters, dispensing with the use of sensors. If the estimates are accurate enough, a pump can be modelled and integrated into the frequency converter control scheme. This can open the possibility of joint motor and pump monitoring and diagnostics, thereby allowing the detection of reliability-reducing operating states that can lead to additional maintenance costs. The goal of this work is to study the accuracy of rotational speed, torque and shaft power estimates calculated by a frequency converter. Laboratory tests were performed in order to observe estimate behaviour in both steady-state and transient operation. An induction machine driven by a vector-controlled frequency converter, coupled with another induction machine acting as load was used in the tests. The estimated quantities were obtained through the frequency converter’s Trend Recorder software. A high-precision, HBM T12 torque-speed transducer was used to measure the actual values of the aforementioned variables. The effect of the flux optimization energy saving feature on the estimate quality was also studied. A processing function was developed in MATLAB for comparison of the obtained data. The obtained results confirm the suitability of this particular converter to provide accurate enough estimates for pumping applications.

Comparison between dSPACE and NI systems based on real-time intelligent control of a teleoperated hydraulic servo system

The Laboratory of Intelligent Machine researches and develops energy-efficient power transmissions and automation for mobile construction machines and industrial processes. The laboratory's particular areas of expertise include mechatronic machine design using virtual technologies and simulators and demanding industrial robotics. The laboratory has collaborated extensively with industrial actors and it has participated in significant international research projects, particularly in the field of robotics. For years, dSPACE tools were the lonely hardware which was used in the lab to develop different control algorithms in real-time. dSPACE's hardware systems are in widespread use in the automotive industry and are also employed in drives, aerospace, and industrial automation. But new competitors are developing new sophisticated systems and their features convinced the laboratory to test new products. One of these competitors is National Instrument (NI). In order to get to know the specifications and capabilities of NI tools, an agreement was made to test a NI evolutionary system. This system is used to control a 1-D hydraulic slider. The objective of this research project is to develop a control scheme for the teleoperation of a hydraulically driven manipulator, and to implement a control algorithm between human and machine interaction, and machine and task environment interaction both on NI and dSPACE systems simultaneously and to compare the results.

Mathematical modeling and optimal control of malaria

Malaria continues to infect millions and kill hundreds of thousands of people worldwide each year, despite over a century of research and attempts to control and eliminate this infectious disease. Challenges such as the development and spread of drug resistant malaria parasites, insecticide resistance to mosquitoes, climate change, the presence of individuals with subpatent malaria infections which normally are asymptomatic and behavioral plasticity in the mosquito hinder the prospects of malaria control and elimination. In this thesis, mathematical models of malaria transmission and control that address the role of drug resistance, immunity, iron supplementation and anemia, immigration and visitation, and the presence of asymptomatic carriers in malaria transmission are developed. A within-host mathematical model of severe Plasmodium falciparum malaria is also developed. First, a deterministic mathematical model for transmission of antimalarial drug resistance parasites with superinfection is developed and analyzed. The possibility of increase in the risk of superinfection due to iron supplementation and fortification in malaria endemic areas is discussed. The model results calls upon stakeholders to weigh the pros and cons of iron supplementation to individuals living in malaria endemic regions. Second, a deterministic model of transmission of drug resistant malaria parasites, including the inflow of infective immigrants, is presented and analyzed. The optimal control theory is applied to this model to study the impact of various malaria and vector control strategies, such as screening of immigrants, treatment of drug-sensitive infections, treatment of drug-resistant infections, and the use of insecticide-treated bed nets and indoor spraying of mosquitoes. The results of the model emphasize the importance of using a combination of all four controls tools for effective malaria intervention. Next, a two-age-class mathematical model for malaria transmission with asymptomatic carriers is developed and analyzed. In development of this model, four possible control measures are analyzed: the use of long-lasting treated mosquito nets, indoor residual spraying, screening and treatment of symptomatic, and screening and treatment of asymptomatic individuals. The numerical results show that a disease-free equilibrium can be attained if all four control measures are used. A common pitfall for most epidemiological models is the absence of real data; model-based conclusions have to be drawn based on uncertain parameter values. In this thesis, an approach to study the robustness of optimal control solutions under such parameter uncertainty is presented. Numerical analysis of the optimal control problem in the presence of parameter uncertainty demonstrate the robustness of the optimal control approach that: when a comprehensive control strategy is used the main conclusions of the optimal control remain unchanged, even if inevitable variability remains in the control profiles. The results provide a promising framework for the design of cost-effective strategies for disease control with multiple interventions, even under considerable uncertainty of model parameters. Finally, a separate work modeling the within-host Plasmodium falciparum infection in humans is presented. The developed model allows re-infection of already-infected red blood cells. The model hypothesizes that in severe malaria due to parasite quest for survival and rapid multiplication, the Plasmodium falciparum can be absorbed in the already-infected red blood cells which accelerates the rupture rate and consequently cause anemia. Analysis of the model and parameter identifiability using Markov chain Monte Carlo methods is presented.