The potential role of environmental exposures and genomic signaling in development of central nervous system tumors

The etiology of central nervous system tumors (CNSTs) is mainly unknown. Aside from extremely rare genetic conditions, such as neurofibromatosis and tuberous sclerosis, the only unequivocally identified risk factor is exposure to ionizing radiation, and this explains only a very small fraction of cases. Using meta-analysis, gene networking and bioinformatics methods, this dissertation explored the hypothesis that environmental exposures produce genetic and epigenetic alterations that may be involved in the etiology of CNSTs. A meta-analysis of epidemiological studies of pesticides and pediatric brain tumors revealed a significantly increased risk of brain tumors among children whose mothers had farm-related exposures during pregnancy. A dose response was recognized when this risk estimate was compared to those for risk of brain tumors from maternal exposure to non-agricultural pesticides during pregnancy, and risk of brain tumors among children exposed to agricultural activities. Through meta-analysis of several microarray studies which compared normal tissue to astrocytomas, we were able to identify a list of 554 genes which were differentially expressed in the majority of astrocytomas. Many of these genes have in fact been implicated in development of astrocytoma, including EGFR, HIF-1α, c-Myc, WNT5A, and IDH3A. Reverse engineering of these 554 genes using Bayesian network analysis produced a gene network for each grade of astrocytoma (Grade I-IV), and ‘key genes’ within each grade were identified. Genes found to be most influential to development of the highest grade of astrocytoma, Glioblastoma multiforme (GBM) were: COL4A1, EGFR, BTF3, MPP2, RAB31, CDK4, CD99, ANXA2, TOP2A, and SERBP1. Lastly, bioinformatics analysis of environmental databases and curated published results on GBM was able to identify numerous potential pathways and geneenvironment interactions that may play key roles in astrocytoma development. Findings from this research have strong potential to advance our understanding of the etiology and susceptibility to CNSTs. Validation of our ‘key genes’ and pathways could potentially lead to useful tools for early detection and novel therapeutic options for these tumors.

The development of direct ultra-fast PCR for forensic genotyping using short channel microfluidic systems with enhanced sieving matrices

There are situations in which it is very important to quickly and positively identify an individual. Examples include suspects detained in the neighborhood of a bombing or terrorist incident, individuals detained attempting to enter or leave the country, and victims of mass disasters. Systems utilized for these purposes must be fast, portable, and easy to maintain. The goal of this project was to develop an ultra fast, direct PCR method for forensic genotyping of oral swabs. The procedure developed eliminates the need for cellular digestion and extraction of the sample by performing those steps in the PCR tube itself. Then, special high-speed polymerases are added which are capable of amplifying a newly developed 7 loci multiplex in under 16 minutes. Following the amplification, a postage stamp sized microfluidic device equipped with specially designed entangled polymer separation matrix, yields a complete genotype in 80 seconds. The entire process is rapid and reliable, reducing the time from sample to genotype from 1-2 days to under 20 minutes. Operation requires minimal equipment and can be easily performed with a small high-speed thermal-cycler, reagents, and a microfluidic device with a laptop. The system was optimized and validated using a number of test parameters and a small test population. The overall precision was better than 0.17 bp and provided a power of discrimination greater than 1 in 106. The small footprint, and ease of use will permit this system to be an effective tool to quickly screen and identify individuals detained at ports of entry, police stations and remote locations. The system is robust, portable and demonstrates to the forensic community a simple solution to the problem of rapid determination of genetic identity.

Cardiac Neural Crest Cells Affect the Development of the Myocardium and Conduction System in the Mouse

Neural crest cells originate from the dorsal most region of the embryonic neural tube. These cells migrate into several embryonic locations and differentiate into a variety of cell types. Cardiac neural crest (CNC) cells are a set of neural crest progenitors that aid in the proper formation of the cardiac septum, which separates the pulmonary from the systemic circulation. We have used Splotch mice to investigate whether the murine CNC cells play a role during the development oft he myocardium and the conduction system. Splotch mice carry a mutation in the P AX3 transcription factor, and display a problem in CNC cell migration. A scanning-electron-microscopy analysis of Splotch mutant-embryonic-hearts reveals abnormalities in the interventricular septum. In addition, the right and left ventricular cavities appear dilated relative to a wild type heart. Hoechst nuclei staining of Splotch heart cryosections demonstrates a decreased number of cardiomyocytes and a corresponding thinner ventricular wall. The absence of Connexin 40 in the ventricles of Splotch mutants, suggests conduction system defects. These results support the evidence that CNC cell signaling plays a role in modulating the growth and development of murine cardiomyocytes and their differentiation into conductile cells.

Development and evaluation of a geographic information system based method to estimate flooding susceptibility in an area of Broward County, Florida

The objective of this study was to develop a GIS-based multi-class index overlay model to determine areas susceptible to inland flooding during extreme precipitation events in Broward County, Florida. Data layers used in the method include Airborne Laser Terrain Mapper (ALTM) elevation data, excess precipitation depth determined through performing a Soil Conservation Service (SCS) Curve Number (CN) analysis, and the slope of the terrain. The method includes a calibration procedure that uses "weights and scores" criteria obtained from Hurricane Irene (1999) records, a reported 100-year precipitation event, Doppler radar data and documented flooding locations. Results are displayed in maps of Eastern Broward County depicting types of flooding scenarios for a 100-year, 24-hour storm based on the soil saturation conditions. As expected the results of the multi-class index overlay analysis showed that an increase for the potential of inland flooding could be expected when a higher antecedent moisture condition is experienced. The proposed method proves to have some potential as a predictive tool for flooding susceptibility based on a relatively simple approach.

The Development of an Optimized System of Narcotic and Explosive Contraband Mimics for Calibration and Training of Biological Detectors

Current commercially available mimics contain varying amounts of either the actual explosive/drug or the chemical compound of suspected interest by biological detectors. As a result, there is significant interest in determining the dominant chemical odor signatures of the mimics, often referred to as pseudos, particularly when compared to the genuine contraband material. This dissertation discusses results obtained from the analysis of drug and explosive headspace related to the odor profiles as recognized by trained detection canines. Analysis was performed through the use of headspace solid phase microextraction in conjunction with gas chromatography mass spectrometry (HS-SPME-GC-MS). Upon determination of specific odors, field trials were held using a combination of the target odors with COMPS. Piperonal was shown to be a dominant odor compound in the headspace of some ecstasy samples and a recognizable odor mimic by trained detection canines. It was also shown that detection canines could be imprinted on piperonal COMPS and correctly identify ecstasy samples at a threshold level of approximately 100ng/s. Isosafrole and/or MDP-2-POH show potential as training aid mimics for non-piperonal based MDMA. Acetic acid was shown to be dominant in the headspace of heroin samples and verified as a dominant odor in commercial vinegar samples; however, no common, secondary compound was detected in the headspace of either. Because of the similarities detected within respective explosive classes, several compounds were chosen for explosive mimics. A single based smokeless powder with a detectable level of 2,4-dinitrotoluene, a double based smokeless powder with a detectable level of nitroglycerine, 2-ethyl-1-hexanol, DMNB, ethyl centralite and diphenylamine were shown to be accurate mimics for TNT-based explosives, NG-based explosives, plastic explosives, tagged explosives, and smokeless powders, respectively. The combination of these six odors represents a comprehensive explosive odor kit with positive results for imprint on detection canines. As a proof of concept, the chemical compound PFTBA showed promise as a possible universal, non-target odor compound for comparison and calibration of detection canines and instrumentation. In a comparison study of shape versus vibration odor theory, the detection of d-methyl benzoate and methyl benzoate was explored using canine detectors. While results did not overwhelmingly substantiate either theory, shape odor theory provides a better explanation of the canine and human subject responses.

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.

Development of calix[4]arene-functionalized microcantilever array sensing system for the rapid, sensitive and simultaneous detection of metal ions in aqueous solutions

The work described in this thesis was conducted with the aim of: 1) investigating the binding capabilities of calix[4]arene-functionalized microcantilevers towards specific metal ions and 2) developing a new16-microcantilever array sensing system for the rapid, and simultaneous detection of metal ions in fresh water. Part I of this thesis reports on the use of three new bimodal calix[4]arenes (methoxy, ethoxy and crown) as potential host/guest sensing layers for detecting selected ions in dilute aqueous solutions using single microcantilever experimental system. In this work it was shown that modifying the upper rim of the calix[4]arenes with a thioacetate end group allow calix[4]arenes to self-assemble on Au(111) forming complete highly ordered monolayers. It was also found that incubating the microcantilevers coated with 5 nm of Inconel and 40 nm of Au for 1 h in a 1.0 M solution of calix[4]arene produced the highest sensitivity. Methoxy-functionalized microcantilevers showed a definite preference for Ca²⁺ ions over other cationic guests and were able to detect trace concentration as low as 10⁻¹² M in aqueous solutions. Microcantilevers modified with ethoxy calix[4]arene displayed their highest sensitivity towards Sr²⁺ and to a lesser extent Ca²⁺ ions. Crown calix[4]arene-modified microcantilevers were however found to bind selectively towards Cs⁺ ions. In addition, the counter anion was also found to contribute to the deflection. For example methoxy calix[4]arene-modified microcantilever was found to be more sensitive to CaCl₂ over other water-soluble calcium salts such as Ca(NO₃)₂ , CaBr₂ and CaI₂. These findings suggest that the response of calix[4]arene-modified microcantilevers should be attributed to the target ionic species as a whole instead of only considering the specific cation and/or anion. Part II presents the development of a 16-microcantilever sensor setup. The implementation of this system involved the creation of data analysis software that incorporates data from the motorized actuator and a two-axis photosensitive detector to obtain the deflection signal originating from each individual microcantilever in the array. The system was shown to be capable of simultaneous measurements of multiple microcantilevers with different coatings. A functionalization unit was also developed that allows four microcantilevers in the array to be coated with an individual sensing layer one at the time. Because of the variability of the spring constants of different cantilevers within the array, results presented were quoted in units of surface stress unit in order to compare values between the microcantilevers in the array.

Mobile Phones, Sensors & The Crowd: Lessons Learnt From Development of a Real-Time Travel Information System

Postprint

The development of an automated nano sampling handling system for nanometre protein crystallography experiments

As the world's synchrotrons and X-FELs endeavour to meet the need to analyse ever-smaller protein crystals, there grows a requirement for a new technique to present nano-dimensional samples to the beam for X-ray diffraction experiments.The work presented here details developmental work to reconfigure the nano tweezer technology developed by Optofluidics (PA, USA) for the trapping of nano dimensional protein crystals for X-ray crystallography experiments. The system in its standard configuration is used to trap nano particles for optical microscopy. It uses silicon nitride laser waveguides that bridge a micro fluidic channel. These waveguides contain 180 nm apertures of enabling the system to use biologically compatible 1.6 micron wavelength laser light to trap nano dimensional biological samples. Using conventional laser tweezers, the wavelength required to trap such nano dimensional samples would destroy them. The system in its optical configuration has trapped protein molecules as small as 10 nanometres.

The development of an automated nano sampling handling system for nanometne protein crystallography experiments

As the world's synchrotrons and X-FELs endeavour to meet the need to analyse ever-smaller protein crystals, there grows a requirement for a new technique to present nano-dimensional samples to the beam for X-ray diffraction experiments.The work presented here details developmental work to reconfigure the nano tweezer technology developed by Optofluidics (PA, USA) for the trapping of nano dimensional protein crystals for X-ray crystallography experiments. The system in its standard configuration is used to trap nano particles for optical microscopy. It uses silicon nitride laser waveguides that bridge a micro fluidic channel. These waveguides contain 180 nm apertures of enabling the system to use biologically compatible 1.6 micron wavelength laser light to trap nano dimensional biological samples. Using conventional laser tweezers, the wavelength required to trap such nano dimensional samples would destroy them. The system in its optical configuration has trapped protein molecules as small as 10 nanometres.

Review of virtual power plant applications for the power system management and V2G market development

Utilization of renewable energy sources and energy storage systems is increasing with fostering new policies on energy industries. However, the increase of distributed generation hinders the reliability of power systems. In order to stabilize them, a virtual power plant emerges as a novel power grid management system. The VPP has a role to make a participation of different distributed energy resources and energy storage systems. This paper defines core technology of the VPP which are demand response and ancillary service concerning about Korea, America and Europe cases. It also suggests application solutions of the VPP to V2G market for restructuring national power industries in Korea.

Development of a multivariable online monitoring system for the thermoforming process

The thermoforming industry has been relatively slow to embrace modern measurement technologies. As a result researchers have struggled to develop accurate thermoforming simulations as some of the key aspects of the process remain poorly understood. For the first time, this work reports the development of a prototype multivariable instrumentation system for use in thermoforming. The system contains sensors for plug force, plug displacement, air pressure and temperature, plug temperature, and sheet temperature. Initially, it was developed to fit the tooling on a laboratory thermoforming machine, but later its performance was validated by installing it on a similar industrial tool. Throughout its development, providing access for the various sensors and their cabling was the most challenging task. In testing, all of the sensors performed well and the data collected has given a powerful insight into the operation of the process. In particular, it has shown that both the air and plug temperatures stabilize at more than 80C during the continuous thermoforming of amorphous polyethylene terephthalate (aPET) sheet at 110C. The work also highlighted significant differences in the timing and magnitude of the cavity pressures reached in the two thermoforming machines. The prototype system has considerable potential for further development. 

Development of a Wireless MEMS Multifunction Sensor System and Field Demonstration of Embedded Sensors for Monitoring Concrete Pavements, TR-637, 2016

Pavements tend to deteriorate with time under repeated traffic and/or environmental loading. By detecting pavement distresses and damage early enough, it is possible for transportation agencies to develop more effective pavement maintenance and rehabilitation programs and thereby achieve significant cost and time savings. The structural health monitoring (SHM) concept can be considered as a systematic method for assessing the structural state of pavement infrastructure systems and documenting their condition. Over the past several years, this process has traditionally been accomplished through the use of wired sensors embedded in bridge and highway pavement. However, the use of wired sensors has limitations for long-term SHM and presents other associated cost and safety concerns. Recently, micro-electromechanical sensors and systems (MEMS) and nano-electromechanical systems (NEMS) have emerged as advanced/smart-sensing technologies with potential for cost-effective and long-term SHM. This two-pronged study evaluated the performance of commercial off-the-shelf (COTS) MEMS sensors embedded in concrete pavement (Final Report Volume I) and developed a wireless MEMS multifunctional sensor system for health monitoring of concrete pavement (Final Report Volume II).

Integration of learning and practice as part of the educational system development in Eritrea. "School Management" - a distance learning program by technical university of Kaiserslautern

The distance learning program "School Management" supports decision makers at the school and ministerial levels in the shaping of formal and informal learning processes at different levels in schools and curricula in Eritrea. This paper examines how the distance learning program is interconnected to educational system development. (DIPF/Orig.)