VictorJuiz/thesis huggingface dataset:
Androgens reverse ovarian epithelial cell growth suppression by TGF-beta1 and regulate the expression of TGF-beta receptors and steroid receptor co-activators

The objective of this thesis is to study the role of androgen in the development of ovarian cancer. My initial observation was that dihydrotestosterone (DHT) down-regulated expression of TGF-β receptors in ovarian cancer cell lines, as determined by quantitative RT-PCR. In order to relate this result to the known growth inhibitory action of TGF-β cultured ovarian surface epithelial cells derived from (1) normal women (OSE) and (2) carriers of germline BRCA1/2 mutations (OSEb), as well as cultured malignant cells from ascites of ovarian cancer patients (OVCAS) were treated with TGF-β1 in the presence or absence of DHT. TGF-β1 inhibited growth in 12/13 cultures and DHT treatment prevented this growth inhibition in 5/6 OSE, 1/2 OSEb, and 4/5 OVCAS. Remarkably, this effect of DHT was observed even though all tested cultures expressed very low levels of androgen receptor (AR) as determined by RT-PCR. Therefore the effect of DHT on the expression of TGF-β receptor types I and II as well as the AR co-activators SRC-1, ARA70, and AIB1 was also determined by quantitative RT-PCR. Unlike the results observed in ovarian cancer cell lines, DHT either up-regulated or downregulated TGF-β receptor transcripts in these primary cultures. Intriguingly, TGF-β receptors, SRC-1, and ARA70 transcripts were either up- or down-regulated synchronously in OSE, but not in OSEb or OVCAS. These studies demonstrate first that androgen can block TGF-β induced growth inhibition in malignant and non-malignant ovarian epithelial cells, in some cases by down-regulating TGF-β receptors. Second, since the steroid receptor co-activators ARA70, SRC-1 and AIB1 are not exclusive for AR, their regulation by androgen suggests a mechanism whereby androgen could influence the action of other steroid hormones such as estrogen and progesterone on ovarian epithelial cells. Third, the lack of coordinated regulation of target gene expression by androgen in OSEb and OVCAS as opposed to OSE, provides the first phenotypic link between ovarian epithelial cells bearing a BRCA1/2 mutation and ovarian cancer cells. This opens up the possibility that androgen could influence the progression of predisposed cells bearing BRCA1/2 mutations to ovarian cancer.

Keywords: Cellular biology
Molecular biology
Advisor: Brown, Theodore J
Letarte, Michelle
Androgen-dependent growth suppression and eventual death in PC-3 prostatic cell cultures expressing a full-length human androgen receptor

Several clonal lines of PC-3 cells (human androgen-independent prostate cancer cells) transfected with an episomal vector (pCEP4) containing a full-length human androgen receptor (AR) cDNA were developed (PC-3(AR) cells). These clonal lines, expressed varying levels of a 110 kDa AR that bracketed the concentration measured in androgen-sensitive LNCaP human prostate cancer cells. The expressed ectopic receptor was viable and capable of inducing the expression of the androgen-sensitive MMTV-luciferase but not the hormone-insensitive RSV-luciferase. This activation of luciferase activity by adrogen was inhibited by the AR antagonist hydroxyflutamide. Treatment of these cells with androgen produced a paradoxical growth inhibition response and that appeared to culminate in cell death. It is hoped that the PC-3(AR) clonal cell lines established and characterized in this thesis will serve as useful models to assess AR action in prostate cancer. Work in these cell lines may establish a viable approach to the treatment of prostate cancer.

Keywords: Cellular biology
Oncology
Advisor: Brown, T J
A Method for Quantitative Interpretation of Wideband, Drill-Hole EM Surveys in Mineral Exploration

Drill-hole geophysical surveys are an obvious means of extending the search for massive-sulphide deposits to depths which are inaccessible to conventional surface exploration techniques. The present investigation combines field and model studies of an EM prospecting method which utilizes a large, fixed transmitter loop with a downhole axial-component magnetic field sensor. Such a system is shown to be well suited to the task of detecting deeply buried massive-sulphide conductors located in resistive host rocks at appreciable distances from the drill hole. The thesis proposes a technique whereby drill hole survey data collected with a wideband large-loop EM system can be routinely interpreted on a quantitative basis. Systems using impulse-like, step-function or frequency-domain waveforms are considered. The interpretation technique is based on forward EM modelling using two simple conductor shapes: a thin, rectangular plate and a two-layer sphere. The analysis is facilitated by "eigencurrent" decomposition of the induced current vortex into a set of non-interacting loops with simple RL-circuit behaviour. The solutions have been implemented in interactive computer programs which are fast, inexpensive and sufficiently versatile to accommodate the configurations and waveforms used in many practical EM systems. The diffusive nature of the inductive process dictates that both stationary (spatially dependent) and dynamic (time or frequency dependent) properties are important in the diagnosis of three-dimensional targets. Model fitting using the stationary characteristics of the anomaly profile allows a first estimate of target parameters such as location, shape and attitude. Direction to the conductor may be difficult to determine unambiguously. The dynamic properties of the eddy currents, which may be observed with particular sensitivity near null points in the anomaly profile, are a useful basis for refining the interpretation. As shown by scale-model experiments, the dynamic aspects of the response are affected by departures from the simple models. Mineralization which is significantly thicker away from the drill hole may reveal itself in field observations through such effects. Field studies carried out at test sites in the Sudbury and Noranda base-metal mining areas near known deposits indicate that many of the important effects predicted by the model studies are, indeed, observed in nature. The results presented in the thesis are intended to serve as guidelines during the model-fitting process and to help exploit 'the inherent advantages of the large-loop EM method. It is recommended that computer modelling be applied both at the design and at the interpretation stages of a survey. Simulation of a three-component system suggests that such measurements would be a significant improvement, as the two transverse components can help resolve ambiguities in the location of the target.

Keywords: Geophysics
Advisor: West, G. F.
The Inductive Response of Thin Plates in a Stratified Space

The equivalent source method, the method whereby conductors are replaced by induced current distributions, can be a valuable tool for solving EM problems. The method can be used to reduce problems with complex analytical solutions into ones which have a simple numerical formulation. This is accomplished by replacing conductors with predetermined source currents of unknown amplitude. The Green's functions of complex spaces can therefore be replaced with the free space Green's function or other simpler Green's functions. The choice of which conductors to replace with induced currents, and consequently which Green's function to use is merely a matter of convenience. This approach is applied to solve for the EM response of two or more plates in a stratified space by invoking the Galerkin method. The plates were replaced with predetermined current distributions and their interactions were computed using the Green's functions for a stratified space. A program was then written to demonstrate the feasibility of the method. Results of the program were compared with the results of the existing programs and with scale model experiments. Computational problems were encountered when calculating the responses of plates in a layered Earth, due to the excessive time required to calculate the Green's functions. However, the results for plates in free space agreed well enough with model experiments to confirm that the method works.

Keywords: Geophysics
Advisor: West, G. F.
Scale Models on Transient Response of Multiple Conductors

The multiple conductor model is used to explain characteristics of the transient response of extensive conductors near a large horizontal transmitter loop. The transient response of two interacting circuits can be expressed in terms of a sum of exponential decays. Scale models of two extensive conductors near a large transmitter loop show the same response characteristics as a simple sum of the two individual conductor responses. A large conductor behind the transmitter can affect the response of a conductor surveyed on a profile line. On the other hand, a conductor between a second conductor and the transmitter blanks the second conductor. Scale models with conductive solution show that a conductive medium increases the interaction between two conductors at early times. Some UTEM field survey responses are compared to results of scale models of extensive conductors. In a first case, the late time anomaly can be fitted to the response of scale models in free space. The early times characteristics are the same as observed over conductors in electrolytic solutions. The data of the second case can be fitted qualitatively to the response of scale models in free air.

Keywords: Geophysics
Advisor: West, G. F.
Geophysical Prospecting with Electric Fields from an Inductive EM Source

It is possible when carrying out EM surveys for mining exploration to measure the electric (E) as well as the magnetic (H) components. Such measurements have been made at several sites with the UTEM time-domain, fixed transmitter EM system. The object of this thesis is to provide a comprehensive basis for the interpretation of such data. It is shown that three distinct EM phenomena are involved, which have clearly separable effects on data recorded with a time-domain, step-response system such as UTEM. At low enough frequencies (in frequency domain), or at sufficiently long times after a step change in primary E field, the observed electric field consists of the divergence-free primary E field and a curl-free secondary E field that arises from charges induced in regions where the conductivity changes. The response at the limit, called the resistive limit E (RLE) field response has been calculated for a number of geologically reasonable bodies. RLE model responses can be found which fit late-time UTEM E field data in many cases. Additional geological information, particularly about resistive features is obtained from the RLE response that is not interpretable from the magnetic EM components alone. EM prospecting conventionally uses a magnetic receiver to detect the secondary fields of induced current flow, and interpretation of the conductivity structure of the ground is per-, formed using the time or frequency dependent nature of the response. The secondary induced currents create a secondary vi divergence-free electric field which through boundary interactions also contributes to the secondary curl-free E field although this latter contribution is usually small. Divergence-free E and H field anomalies (when normalized to their respective primary fields) are not of identical magnitude or form, but are related to the geometry of the induced current flow. Simple circuit estimates, together with limited scale modelling were used to predict the E field inductive anomalies for some simple models. These results were used to interpret UTEM survey data, and it was found that by including the E fields that estimates of the geometry of secondary current flow could be improved over those using H field data alone in some cases. Conventional induced polarization (IP) surveys show that many earth materials have a frequency dependent conductivity. The effects of polarizable bodies of simple shape on E fields were calculated for an inductive EM source field. The predicted effects are able to explain observed anomalous late-time UTEM E field data quantitatively. As in the case of MIP (IP surveys using a grounded transmitter and magnetic receiver) no IP anomaly is generated in the resistive limit by horizontal layers of polarizable material. Due to geometrical complications, and because the UTEM sampling times are designed to define EM time decays and do not cover a very wide time range with respect to IP effects, characterization of fundamental IP parameters can only be done in special cases.

Keywords: Geophysics
Advisor: West, G. F.
Detection of Hydrocarbon Accumulations by Surface Electrical Methods - A Feasibility Study

Theoretical aspects of an electrical exploration technique to directly detect hydrocarbon accumulations based on their high resistivity are investigated. Oil fields, because of their large areal extent, can often be approximated by thin, laterally infinite layers. The depth sounding system proposed to detect thin resistive layers has a grounded, time domain transmitter and receivers capable of measuring the magnetic and electric fields generated by the transmitter. Based on this system concept, a detectability study for thin resistive layers at large depths has been carried out by means of computer modelling. To estimate noise levels that would be encountered in a field experiment, a field test was conducted in an area of stratified sediments in Southern Ontario. Using the steady state value of the electric field, the transient response of the electric field in two horizontal directions and the transient response of the vertical component of the magnetic field, it is theoretically possible to detect thin resistive layers down to a depth of about 2000 meters, even in the presence of "geological noise".

Keywords: Geophysics
Advisor: West, G. F.
Applications of wide Band Time Domain EM Measurements in Mineral Exploration

Electromagnetic prospecting measurements must be made over a wider band of frequencies if they are to be effective in terrains with complicated conductivity structures. A system (UTEM) was designed to do such measurements systematically and practically in the time domain. It is a ground method using a large transmitter loop and a single receiver coil. The transmitted current has a precise triangular waveform at a frequency of 30 Hz. In the receiver, there are eight sampling channels corresponding to delay times decreasing according to a binary geometric progression. The UTEM system has many unusual characteristics: it can measure both electric and magnetic fields; the transmitted waveform concentrates the power at lower frequencies and has no off times; the measuring channels sample virtually the whole waveform. Field measurements were made at five test sites. The data from a field survey in a stratified environment were interpreted by developing numerical methods for inverting the observed data in terms of layered models. In order to explain the other field results, a variety of idealized models were studied by time-domain scale models measurements and by conversion of frequency domain model data. Very few of the field responses can be completely explained in terms of free-air models. However, the late portion of measured transient decays can often be explained in this fashion. The more complicated responses which occur at early sampling times can be explained in terms of two main effects -- "blanking" and "current gathering". These were studied by means of idealized models. The "blanking" effect is the disappearance of the response at early times caused by shielding of a local conductor by a conductive overburden which is not in contact with it. The "current gathering" effect is an enhancement of the response at early times (but after "blanking") which is caused by the channelling of regionally induced host-rock currents into a local conductor. Current gathering is the most prevalent in the field responses. In the documented examples, it appears to be due to the presence of a diffuse conductive "halo" surrounding the main (sulphide) conductors. Some unexpected field responses which appeared on the later channels have been tentatively explained as inductive induced polarization (IIP) effects. The computed responses of some simple polarizable models explain some of the features of the field responses but they indicate that with magnetic field measurements, IIP effects would be detectable only for high chargeabilities. IIP effects in electric field data are more detectable. Since these cannot be explained as magnetic responses, the observed electric field responses are regarded as more conclusive field evidences of IIP responses. The electric field IIP responses are apparently excited by regional host rock currents being channeled into metallic conductors and may be used to identify metallic conductors.

Keywords: Geophysics
Advisor: West, G. F.
The electromagnetic Response of a Conductive Inhomogeneity In a Layered Earth

In this thesis, the integral equation technique is used to model the electromagnetic prospecting problem of a conductive inhomogeneity embedded in a layered earth environment. Basically, it consists of replacing the anomalous conductor, which is simplified to a finite vertical thin plate, by a surface of scattering currents. The plate is sampled on a sqare grid and the number of points is kept to a minimum by using a fifth degree spline moment function to interpolate between them. In order to bypass the numerical problems encountered when attempting to solve directly for the components of electric field at each grid point, the integral equation is expressed in terms of two potentials representing divergence free current flow through its surface. Calculations involving the layered earth are done with a new Fast Fourier transform approach which basically consists of solving this problem in the Catesian wavenumber domain, i.e. the 2-D Fourier transform of the horizontal plane. The results show that a conductive host and/or overburden will affect the amplitude, phase and width of the conductor's free air anomaly. Both the host and the overburden will cause an attenuation and phase rotation of the source fields to the plate and the anomalous fields from the plate. When the target conductor is in contact with a conductive host, the channelling of currents induced in the host is found to increase the anomaly amplitude substantially. Computation costs do not permit the generation of high accuracy type curves, but the model examples presented demonstrate the basic physics of conductive earth effects in electromagnetic prospecting.

Keywords: Geophysics
Advisor: West, G. F.
Extraction of nonstationary sinusoids

A novel method of extraction of nonstationary sinusoids and estimation of their parameters is presented. The proposed algorithm has a nonlinear structure which renders it fully adaptive in tracking time-variations in the parameters of the targeted sinusoid including its phase and frequency. Mathematical properties of the differential equations governing the proposed algorithm are presented and the performance of the proposed algorithm is demonstrated with the aid of computer simulations. The proposed algorithm has been digitally implemented on a digital signal processor (DSP) platform and the laboratory verification of its performance is presented. Superiority of the proposed algorithm over conventional Fourier analysis and linear adaptive methods is demonstrated by its successful application to a number of real problems. Elimination of sinusoidal disturbances under time-varying conditions is a challenging problem of current research. The proposed algorithm is entployed to construct an adaptive notch filter for the rejection of quasi-periodic interferences. Its performance is exemplified by its application to the problem of elimination of power line noise potentially present on electrocardiogram and telephone cables. Application of the proposed algorithm in the estimation of low-level biomedical signals polluted by noise constitutes another example of its superior performance over conventional methods. Refinement and analysis of ultrasonic waves used in non-destructive testing (NDT) of materials is presented as another useful application of the proposed algorithm. Finally, estimation of instantaneous frequency in noise, exemplified by Doppler frequency shift estimation, is demonstrated. The proposed algorithm exhibits a high degree of immunity with regard to both external noise and internal parameter settings while offering structural simplicity crucial for real-time applications.

Keywords: Applied sciences
Digital signal processing
Ultrasonic waves
A case study analysis of Ontario CAAT graduates who transfer to a university

Ontario Colleges of Applied Arts and Technology were established to educate the Grade 12 graduate who was not destined for university, in an educational sector meant to be separate from universities. Even though the original mandate and focus of Ontario CAATs has been on the employment of their graduates, students have been moving from colleges to universities since inception. However, very little is known about transfer and the characteristics of the transfer student in the province of Ontario. As well, there is limited empirical evidence regarding the extent of success for college transfer students at the universities. The purpose of this study was to describe and analyze the demographic and academic characteristics of college-to-university students and to provide information on their performance at university. Using an exploratory case study of Seneca College graduates, the thesis profiles the typical transfer student, documents their performance and persistence at university, and compares them to other college graduates. A questionnaire was developed and mailed to all students who had graduated from Seneca College and who had subsequently enrolled at a university as determined by their responses to the Graduate Satisfaction Survey (GSS) from 1998-99 to 2002-03. The returned questionnaires were linked with the corresponding responses to the GSS and the respondents' records on the college's Administration and Registration Information Exchange System (ARIES). Together the information gathered included data regarding age, gender, language, citizenship, aspirations, and socio-economic status of the transfer student; the college program from which they graduated and the university program into which they enrolled; and, their success at university. The evidence suggests that an increasing number of younger students entered Seneca College directly from high school with a conscious design to use their program and the school itself as a vehicle to enter university. Not all the programs were developed to achieve that end, nor were the pathways explicitly planned; however, the students appeared to understand the college to be a viable route to realize their goal of attending university and entered Seneca College for this purpose, expecting it to provide that opportunity. The research also shows that the route to university could only have been through the college for a large majority of these transfer students because they would not have met the university entrance requirements based on their pre-college credentials. Finally, the university-through-college process appears to be providing access to higher education and university for families with limited post-secondary experience and who come from the middle to lower socio-economic strata. Based on these results and the process for ascertaining the data, a consistent approach to measuring transfer is proposed along with curriculum and program recommendations for increasing transfer provincially.

Keywords: Education
Ontario
University
Colleges of applied arts and technology
Transfer students