Design and construction of a new Drosophila species, D.synthetica, by synthetic regulatory evolution

Here, I merge the principles of synthetic biology1,2 and regulatory evolution3-11 to create a new species12-15 with a minimal set of known elements. Using preexisting transgenes and recessive mutations of Drosophila melanogaster, a transgenic population arises with small eyes and a different venation pattern that fulfills the criteria of a new species according to Mayr's "Biological Species Concept"7,10. The genetic circuit entails the loss of a non-essential transcription factor and the introduction of cryptic enhancers. Subsequent activation of those enhancers causes hybrid lethality. The transition from "transgenic organisms" towards "synthetic species", such as Drosophila synthetica, constitutes a safety mechanism to avoid hybridization with wild type populations and preserve natural biodiversity16-18. Drosophila synthetica is the first transgenic organism that cannot hybridize with the original wild type population but remains fertile when crossed with other transgenic animals.

Design and Development of an FPGA-based Distributed Computing Processing Platform

This thesis presents two frameworks- a software framework and a hardware core manager framework- which, together, can be used to develop a processing platform using a distributed system of field-programmable gate array (FPGA) boards. The software framework providesusers with the ability to easily develop applications that exploit the processing power of FPGAs while the hardware core manager framework gives users the ability to configure and interact with multiple FPGA boards and/or hardware cores. This thesis describes the design and development of these frameworks and analyzes the performance of a system that was constructed using the frameworks. The performance analysis included measuring the effect of incorporating additional hardware components into the system and comparing the system to a software-only implementation. This work draws conclusions based on the provided results of the performance analysis and offers suggestions for future work.

Design and Use of an Alternative Fuel Testing Apparatus and Assessment of the Feasibility of Biodiesel

Petroleum supply and environmental pollution issues constantly increase interest in renewable low polluting alternative fuels. Published test results show decreased pollution with similar power output and fuel consumption from Internal Combustion Engines (ICE) burning alternative fuels. More specifically, diesel engines burning biodiesel derived from plant oils and animal fats not only reduce harmful exhaust emissions but are renewable and environmentally friendly. To validate these claims and assess the feasibility of alternative fuels, independent engine dynamometer and emissions testing was performed. A testing apparatus capable of making relevant measurements was designed, built, and used to test and determine the feasibility of biodiesel. The apparatus marks the addition of a valuable testing tool to the University and provides a foundation for future experiments. This thesis will discuss the background of biodiesel, testing methods, design and function of the testing apparatus, experimental results, relevant calculations, and conclusions.

Design and Preliminary Results of an Atmospheric-Pressure Model Gas Turbine Combustor Utilizing Varying CO2 Doping Concentration in CH4 to Emulate Biogas Combustion

Utilization of biogas can provide a source of renewable energy in both heat and power generation. Combustion of biogas in land-based gas turbines for power generation is a promising approach to reducing greenhouse gases and US dependence on foreign-source fossil fuels. Biogas is a byproduct from the decomposition of organic matter and consists primarily of CH4 and large amounts of CO2. The focus of this research was to design a combustion device and investigate the effects of increasing levels of CO2 addition to the combustion of pure CH4 with air. Using an atmospheric-pressure, swirl-stabilized dump combustor, emissions data and flame stability limitations were measured and analyzed. In particular, CO2, CO, and NOx emissions were the main focus of the combustion products. Additionally, the occurrence of lean blowout and combustion pressure oscillations, which impose significant limitations in operation ranges for actual gas turbines, was observed. Preliminary kinetic and equilibrium modeling was performed using Cantera and CEA for the CH4/CO2/Air combustion systems to analyze the effect of CO2 upon adiabatic flame temperature and emission levels. The numerical and experimental results show similar dependence of emissions on equivalence ratio, CO2 addition, inlet air temperature, and combustor residence time. (C) 2014 Elsevier Ltd. All rights reserved.

Model-based control of neuromuscular block using mivacurium: design and clinical verification

BACKGROUND: Short-acting agents for neuromuscular block (NMB) require frequent dosing adjustments for individual patient's needs. In this study, we verified a new closed-loop controller for mivacurium dosing in clinical trials. METHODS: Fifteen patients were studied. T1% measured with electromyography was used as input signal for the model-based controller. After induction of propofol/opiate anaesthesia, stabilization of baseline electromyography signal was awaited and a bolus of 0.3 mg kg-1 mivacurium was then administered to facilitate endotracheal intubation. Closed-loop infusion was started thereafter, targeting a neuromuscular block of 90%. Setpoint deviation, the number of manual interventions and surgeon's complaints were recorded. Drug use and its variability between and within patients were evaluated. RESULTS: Median time of closed-loop control for the 11 patients included in the data processing was 135 [89-336] min (median [range]). Four patients had to be excluded because of sensor problems. Mean absolute deviation from setpoint was 1.8 +/- 0.9 T1%. Neither manual interventions nor complaints from the surgeons were recorded. Mean necessary mivacurium infusion rate was 7.0 +/- 2.2 microg kg-1 min-1. Intrapatient variability of mean infusion rates over 30-min interval showed high differences up to a factor of 1.8 between highest and lowest requirement in the same patient. CONCLUSIONS: Neuromuscular block can precisely be controlled with mivacurium using our model-based controller. The amount of mivacurium needed to maintain T1% at defined constant levels differed largely between and within patients. Closed-loop control seems therefore advantageous to automatically maintain neuromuscular block at constant levels.

Design and in vitro characterization of highly sst2-selective somatostatin antagonists suitable for radiotargeting

Radiolabeled sst 2 and sst 3 antagonists are better candidates for tumor targeting than agonists with comparable binding characteristics (Ginj, M.; Zhang, H.; Waser, B.; Cescato, R.; Wild, D.; Erchegyi, J.; Rivier, J.; Mäcke, H. R.; Reubi, J. C. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 16436-16441.). Because most of the neuroendocrine tumors express sst 2, we used the known antagonists acetyl- pNO 2Phe (2)- c[ dCys (3)-Tyr (7)- dTrp (8)-Lys (9)-Thr (10)-Cys (14)]- dTyr (15)-NH 2 ( 1) (Bass, R. T.; Buckwalter, B. L.; Patel, B. P.; Pausch, M. H.; Price, L. A.; Strnad, J.; Hadcock, J. R. Mol. Pharmacol. 1996, 50, 709-715. Bass, R. T.; Buckwalter, B. L.; Patel, B. P.; Pausch, M. H.; Price, L. A.; Strnad, J.; Hadcock, J. R. Mol. Pharmacol. 1997, 51, 170; Erratum.) and H-Cpa (2)- c[ dCys (3)-Tyr (7)- dTrp (8)-Lys (9)-Thr (10)-Cys (14)]-2Nal (15)-NH 2 ( 7) (Hocart, S. J.; Jain, R.; Murphy, W. A.; Taylor, J. E.; Coy, D. H. J. Med. Chem. 1999, 42, 1863-1871.) as leads for analogues with increased sst 2 binding affinity and selectivity. Among the 32 analogues reported here, DOTA- pNO 2Phe (2)- c[ dCys (3)-Tyr (7)- dAph (8)(Cbm)-Lys (9)-Thr (10)-Cys (14)- dTyr (15)-NH 2 ( 3) and DOTA-Cpa (2)- c[ dCys (3)-Aph (7)(Hor)- dAph (8)(Cbm)-Lys (9)-Thr (10)-Cys (14)]- dTyr (15)-NH 2 ( 31) had the highest sst 2 binding affinity and selectivity. All of the analogues tested kept their sst 2 antagonistic properties (i.e., did not affect calcium release in vitro and competitively antagonized the agonistic effect of [Tyr (3)]octreotide). Moreover, in an immunofluorescence-based internalization assay, the new analogues prevented sst 2 internalization induced by the sst 2 agonist [Tyr (3)]octreotide without being active by themselves. In conclusion, several analogues (in particular 3, 31, and 32) have outstanding sst 2 binding and functional antagonistic properties and, because of their DOTA moiety, are excellent candidates for in vivo targeting of sst 2-expressing cancers.