Design and synthesis of S-ribosylhomocysteine analogues

Bacteria are known to release a large variety of small molecules known as autoinducers (AI) which effect quorum sensing (QS) initiation. The interruption of QS effects bacterial communication, growth and virulence. ^ Three novel classes of S-ribosylhomocysteine (SRH) analogues as potential inhibitors of S-ribosylhomocysteinase (LuxS enzyme) and AI-2 modulators of QS were developed. The synthesis of 2-deoxy-2-bromo-SRH analogues was attempted by coupling of the corresponding 2-bromo-2-deoxypentafuranosyl precursors with the homocysteinate anion. The displacement of the bromide from C2 rather than the expected substitution of the mesylate from C5 was observed. The synthesis of 4-C-alkyl/aryl-S-ribosylhomocysteine analogues involved the following steps: (i) conversion of the D-ribose to the ribitol-4-ulose; (ii) diastereoselective addition of various alkyl or aryl or vinyl Grignard reagents to 4-ketone intermediate; (iii) oxidation of the primary hydroxyl group at C1 followed by the intramolecular ring closure to the corresponding 4-C-alkyl/aryl-substituted ribono-1,4-lactones; (iv) displacement of the activated 5-hydroxyl group with the protected homocysteinate. Treatment of the 4-C-alkyl/aryl-substituted SRH analogues with lithium triethylborohydride effected reduction of the ribonolactone to the ribose (hemiacetal) and subsequent global deprotection with trifluoroacetic acid provided 4-C-alkyl/aryl-SRHs. ^ The 4-[thia]-SRH were prepared from the 1-deoxy-4-thioribose through the coupling of the &agr;-fluoro thioethers (thioribosyl fluorides) with homocysteinate anion. The 4-[thia]-SRH analogues showed concentration dependent effect on the growth on las (50% inhibitory effect at 200 µg/mL). The most active was 1-deoxy-4-[thia]-SRH analogue with sufur atom in the ring oxidized to sulfoxide decreasing las gene activity to approximately 35% without affecting rhl gene. Neither of the tested compounds had effect on bioluminescence nor on total growth of V. harveyi, but had however slight inhibition of the QS.^

Design and development of a one-degree-of-freedom force-reflecting manual controller prototype for teleoperation

The present research is carried out from the viewpoint of primarily space applications where human lives may be in danger if they are to work under these conditions. This work proposes to develop a one-degree-of-freedom (1-DOF) force-reflecting manual controller (FRMC) prototype for teleoperation, and address the effects of time delays commonly found in space applications where the control is accomplished via the earth-based control stations. To test the FRMC, a mobile robot (PPRK) and a slider-bar were developed and integrated to the 1-DOF FRMC. The software developed in Visual Basic is able to telecontrol any platform that uses an SV203 controller through the internet and it allows the remote system to send feedback information which may be in the form of visual or force signals. Time delay experiments were conducted on the platform and the effects of time delay on the FRMC system operation have been studied and delineated.

Design and construction of a portable force-reflecting manual controller for teleoperation systems

A man-machine system called teleoperator system has been developed to work in hazardous environments such as nuclear reactor plants. Force reflection is a type of force feedback in which forces experienced by the remote manipulator are fed back to the manual controller. In a force-reflecting teleoperation system, the operator uses the manual controller to direct the remote manipulator and receives visual information from a video image and/or graphical animation on the computer screen. This thesis presents the design of a portable Force-Reflecting Manual Controller (FRMC) for the teleoperation of tasks such as hazardous material handling, waste cleanup, and space-related operations. The work consists of the design and construction of a prototype 1-Degree-of-Freedom (DOF) FRMC, the development of the Graphical User Interface (GUI), and system integration. Two control strategies - PID and fuzzy logic controllers are developed and experimentally tested. The system response of each is analyzed and evaluated. In addition, the concept of a telesensation system is introduced, and a variety of design alternatives of a 3-DOF FRMC are proposed for future development.

Design and development of an enzyme-linked biosensor for detection and quantification of phosphate species

The objective of this study is to design and development of an enzyme-linked biosensor for detection and quantification of phosphate species. Various concentrations of phosphate species were tested and completed for this study. Phosphate is one of the vital nutrients for all living organisms. Phosphate compounds can be found in nature (e.g., water sediments), and they often exist in aninorganic form. The amount of phosphates in the environment strongly influences the operations of living organisms. Excess amount of phosphate in the environment causes eutrophication which in turn causes oxygen deficit for the other living organisms. Fish die and degradation of habitat in the water occurs as a result of eutrophication. In contrast, low phosphate concentration causes death of vegetation since plants utilize the inorganic phosphate for photosynthesis, respiration, and regulation of enzymes. Therefore, the phosphate quantity in lakes and rivers must be monitored. Result demonstrated that phosphate species could be detected in various organisms via enzyme-linked biosensor in this research.

Formal verification and testing of software architectural models

Ensuring the correctness of software has been the major motivation in software research, constituting a Grand Challenge. Due to its impact in the final implementation, one critical aspect of software is its architectural design. By guaranteeing a correct architectural design, major and costly flaws can be caught early on in the development cycle. Software architecture design has received a lot of attention in the past years, with several methods, techniques and tools developed. However, there is still more to be done, such as providing adequate formal analysis of software architectures. On these regards, a framework to ensure system dependability from design to implementation has been developed at FIU (Florida International University). This framework is based on SAM (Software Architecture Model), an ADL (Architecture Description Language), that allows hierarchical compositions of components and connectors, defines an architectural modeling language for the behavior of components and connectors, and provides a specification language for the behavioral properties. The behavioral model of a SAM model is expressed in the form of Petri nets and the properties in first order linear temporal logic. This dissertation presents a formal verification and testing approach to guarantee the correctness of Software Architectures. The Software Architectures studied are expressed in SAM. For the formal verification approach, the technique applied was model checking and the model checker of choice was Spin. As part of the approach, a SAM model is formally translated to a model in the input language of Spin and verified for its correctness with respect to temporal properties. In terms of testing, a testing approach for SAM architectures was defined which includes the evaluation of test cases based on Petri net testing theory to be used in the testing process at the design level. Additionally, the information at the design level is used to derive test cases for the implementation level. Finally, a modeling and analysis tool (SAM tool) was implemented to help support the design and analysis of SAM models. The results show the applicability of the approach to testing and verification of SAM models with the aid of the SAM tool.

Design and implementation of a web based shop floor control system to maintain schedule feasibility in a dynamic job shop environment

The effective control of production activities in dynamic job shop with predetermined resource allocation for all the jobs entering the system is a unique manufacturing environment, which exists in the manufacturing industry. In this thesis a framework for an Internet based real time shop floor control system for such a dynamic job shop environment is introduced. The system aims to maintain the schedule feasibility of all the jobs entering the manufacturing system under any circumstance. The system is capable of deciding how often the manufacturing activities should be monitored to check for control decisions that need to be taken on the shop floor. The system will provide the decision maker real time notification to enable him to generate feasible alternate solutions in case a disturbance occurs on the shop floor. The control system is also capable of providing the customer with real time access to the status of the jobs on the shop floor. The communication between the controller, the user and the customer is through web based user friendly GUI. The proposed control system architecture and the interface for the communication system have been designed, developed and implemented.

Design and Development of Geographical Information System (GIS) Map for Nuclear Waste Streams

A nuclear waste stream is the complete flow of waste material from origin to treatment facility to final disposal. The objective of this study was to design and develop a Geographic Information Systems (GIS) module using Google Application Programming Interface (API) for better visualization of nuclear waste streams that will identify and display various nuclear waste stream parameters. A proper display of parameters would enable managers at Department of Energy waste sites to visualize information for proper planning of waste transport. The study also developed an algorithm using quadratic Bézier curve to make the map more understandable and usable. Microsoft Visual Studio 2012 and Microsoft SQL Server 2012 were used for the implementation of the project. The study has shown that the combination of several technologies can successfully provide dynamic mapping functionality. Future work should explore various Google Maps API functionalities to further enhance the visualization of nuclear waste streams.

Design and Implementation of a Cloud Infrastructure for Distributed Scientific Calculation

Cloud computing enables independent end users and applications to share data and pooled resources, possibly located in geographically distributed Data Centers, in a fully transparent way. This need is particularly felt by scientific applications to exploit distributed resources in efficient and scalable way for the processing of big amount of data. This paper proposes an open so- lution to deploy a Platform as a service (PaaS) over a set of multi- site data centers by applying open source virtualization tools to facilitate operation among virtual machines while optimizing the usage of distributed resources. An experimental testbed is set up in Openstack environment to obtain evaluations with different types of TCP sample connections to demonstrate the functionality of the proposed solution and to obtain throughput measurements in relation to relevant design parameters.

Design and development of a Unity based framework for augmented worlds

The way we've always envisioned computer programs is slowly changing. Thanks to the recent development of wearable technologies we're experiencing the birth of new applications that are no more limited to a fixed screen, but are instead sparse in our surroundings by means of fully fledged computational objects. In this paper we discuss proper techniques and technologies to be used for the creation of "Augmented Worlds", through the design and development of a novel framework that can help us understand how to build these new programs.

Ambient vibration tests and analysis of a multiple-span elevated bridge

Peer reviewed

Options to advance co-ordination and analysis of climate data in Europe

Systematic, high-quality observations of the atmosphere, oceans and terrestrial environments are required to improve understanding of climate characteristics and the consequences of climate change. The overall aim of this report is to carry out a comparative assessment of approaches taken to addressing the state of European observations systems and related data analysis by some leading actors in the field. This research reports on approaches to climate observations and analyses in Ireland, Switzerland, Germany, The Netherlands and Austria and explores options for a more coordinated approach to national responses to climate observations in Europe. The key aspects addressed are: an assessment of approaches to develop GCOS and provision of analysis of GCOS data; an evaluation of how these countries are reporting development of GCOS; highlighting best practice in advancing GCOS implementation including analysis of Essential Climate Variables (ECVs); a comparative summary of the differences and synergies in terms of the reporting of climate observations; an overview of relevant European initiatives and recommendations on how identified gaps might be addressed in the short to medium term.

Design and Synthesis of 4-N-Alkanoyl and 4-N-Alkyl Gemcitabine Analogues Suitable for Positron Emission Tomography

Gemcitabine is a highly potent chemotherapeutic nucleoside agent used in the treatment of several cancers and solid tumors. However, it is therapeutically limitated because of toxicity to normal cells and its rapid intracellular deamination by cytidine deaminase into the inactive uracil derivative. Modification at the 4-(N) position of gemcitabine's exocyclic amine to an -amide functionality is a well reported prodrug strategy which has been that confers a resistance to intracellular deamination while also altering pharmacokinetics of the parent drug. Coupling of gemcitabine to carboxylic acids with varying terminal moieties afforded the 4-N-alkanoylgemcitabines whereas reaction of 4-N-tosylgemcitabine with the corresponding alkyl amines gave the 4-N-alkylgemcitabines. The 4-N-alkanoyl and 4-N-alkyl gemcitabine analogues with a terminal hydroxyl group on the 4-N-alkanoyl or 4-N-alkyl chain were efficiently fluorinated either with diethylaminosulfur trifluoride or under conditions that are compatible with the synthetic protocols for 18F labeling, such as displacement of the corresponding mesylate with KF/Kryptofix 2.2.2. The 4-N-alkanoylgemcitabine analogues displayed potent cytostatic activities against murine and human tumor cell lines with 50% inhibitory concentration (IC50) values in the range of low nM, whereas cytotoxicity of the 4-N-alkylgemcitabine derivatives were in the low to modest µM range. The cytostatic activity of the 4-N-alkanoylgemcitabines was reduced by several orders of magnitude in the 2'-deoxycytidine kinase (dCK)-deficient CEM/dCK- cell line while the 4-N-alkylgemcitabines were only lowered by 2-5 times. None of the 4-N-modified gemcitabines were found to be substrates for cytosolic dCK, however all were found to inhibit DNA synthesis. As such, the 4-N-alkanoyl gemcitabine derivatives likely need to be converted to gemcitabine prior to achieving their significant cytostatic potential, whereas the 4-N-alkylgemcitabines reach their modest activity without "measurable" conversion to gemcitabine. Thus, the 4-N-alkylgemcitabines provide valuable insight on the metabolism of 4-N-modified gemcitabine prodrugs.

THE DESIGN AND SYNTHESIS OF SILOXANE PRECURSORS FOR CHIRAL PERIODIC MESOPOROUS ORGANOSILICA MATERIALS

The development of cost-effective and reliable methods for the synthesis and separation of asymmetric compounds is paramount in helping to meet society’s ever-growing demand for chiral small molecules. Of these methods, chiral heterogeneous supports are particularly appealing as they allow for the reuse of the chiral source. One such support, based on the synergy between chiral organic units and structurally stable inorganic silicon scaffolds are periodic mesoporous organosilicas (PMOs). In the work described herein, I examine some of the factors governing the transmission of chirality between chiral dopants and prochiral bulk phases in chiral PMO materials. In particular, the exploration of 1,1’-binaphthalene-bridged chiral dopants with a focus on the point of attachment into the materials. Moreover, the effects of ordering in the materials are examined and reveal that chirality transfer is more facile in materials with molecular-scale order then those containing amorphous walls. Secondly, the issues surrounding the synthesis and purification of aryl-triethoxysilanes as siloxane precursors are addressed. Both the introduction of a two-carbon linker and the direct attachment of allyl and mixed allyldiethoxysilane species are explored. This work demonstrates that allyldiethoxysilanes are ideal, in that they are stable enough to permit facile synthesis, while still being able to hydrolyze completely to produce well-ordered materials. Lastly, the production of new bulk phases for chiral PMO materials is examined by introducing new prochiral nitrogen-containing siloxane precursors. Biphenyldiamine and bipyridine-bridged siloxane precursors are readily synthesized on reasonable scales. Their use as the bulk siloxane precursor in the production of PMO materials however, is precluded by insufficient gelation and additional siloxane precursors are necessary for the production of ordered materials. In addition to the research detailed above that forms the body of this thesis, two short works are appended. The first details the production of polythiophene assemblies mediated through coordination nanospaces, while the second explores the production of N-heterocyclic carbene functionalized gold nanoparticles through ligand exchange.

Design and Implementation of Tools for STM Studies in UHV and at the Solid-Liquid Interface

This thesis presents details of the design and development of novel tools and instruments for scanning tunneling microscopy (STM), and may be considered as a repository for several years' worth of development work. The author presents design goals and implementations for two microscopes. First, a novel Pan-type STM was built that could be operated in an ambient environment as a liquid-phase STM. Unique features of this microscope include a unibody frame, for increased microscope rigidity, a novel slider component with large Z-range, a unique wiring scheme and damping mechanism, and a removable liquid cell. The microscope exhibits a high level of mechanical isolation at the tunnel junction, and operates excellently as an ambient tool. Experiments in liquid are on-going. Simultaneously, the author worked on designs for a novel low temperature, ultra-high vacuum (LT-UHV) instrument, and these are presented as well. A novel stick-slip vertical coarse approach motor was designed and built. To gauge the performance of the motor, an in situ motion sensing apparatus was implemented, which could measure the step size of the motor to high precision. A new driving circuit for stick-slip inertial motors is also presented, that o ffers improved performance over our previous driving circuit, at a fraction of the cost. The circuit was shown to increase step size performance by 25%. Finally, a horizontal sample stage was implemented in this microscope. The build of this UHV instrument is currently being fi nalized. In conjunction with the above design projects, the author was involved in a collaborative project characterizing N-heterocyclic carbene (NHC) self-assembled monolayers (SAMs) on Au(111) films. STM was used to characterize Au substrate quality, for both commercial substrates and those manufactured via a unique atomic layer deposition (ALD) process by collaborators. Ambient and UHV STM was then also used to characterize the NHC/Au(111) films themselves, and several key properties of these films are discussed. During this study, the author discovered an unexpected surface contaminant, and details of this are also presented. Finally, two models are presented for the nature of the NHC-Au(111) surface interaction based on the observed film properties, and some preliminary theoretical work by collaborators is presented.