The demands for efficient utilization of ore bodies and proper risk management in the mining industry have resulted in a new cross-disciplinary subject called geometallurgy. Geometallurgy connects geological, mineral processing and subsequent downstream processing information together to provide a comprehensive model to be used in production planning and management. A geometallurgical program is an industrial application of geometallurgy. Various approaches that are employed in geometallurgical programs include the traditional way, which uses chemical elements, the proxy method, which applies small-scale tests, and the mineralogical approach using mineralogy or the combination of those. The mineralogical approach provides the most comprehensive and versatile way to treat geometallurgical data. Therefore it was selected as a basis for this study. For the mineralogical approach, quantitative mineralogical information is needed both for the deposit and the process. The geological model must describe the minerals present, give their chemical composition, report their mass proportions (modal composition) in the ore body and describe the ore texture. The process model must be capable of using mineralogical information provided by the geological model to forecast the metallurgical performance of different geological volumes and periods. A literature survey showed that areas, where more development is needed for using the mineralogical approach, are: 1) quick and inexpensive techniques for reliable modal analysis of the ore samples; 2) ore textural characterization of the ore to forecast the liberation distribution of the ore when crushed and ground; 3) unit operation models based on particle properties (at mineral liberation level) and 4) a system capable of handling all this information and transferring it to production model. This study focuses on developing tools in these areas. A number of methods for obtaining mineral grades were evaluated with a focus on geometallurgical applicability, precision, and trueness. A new technique developed called combined method uses both quantitative X-ray powder diffraction with Rietveld refinement and the Element-to-Mineral Conversion method. The method not only delivers the required turnover for geometallurgy but also overcomes the shortcomings if X-ray powder diffraction or Element-to-Mineral Conversion were used alone. Characterization of ore texture before and after breakage provides valuable insights about the fracture pattern in comminution, the population of particles for specific ore texture and their relation to parent ore texture. In the context of the mineralogical approach to geometallurgy, predicting the particle population from ore texture is a critical step to establish an interface between geology and mineral processing. A new method called Association Indicator Matrix developed to assess breakage pattern of ore texture and analyze mineral association. The results of ore texture and particle analysis were used to generate particle population from ore texture by applying particle size distribution and breakage frequencies. The outcome matches well with experimental data specifically for magnetite ore texture. In geometallurgy, process models can be classified based on in which level the ore, i.e. the feed stream to the processing plant and each unit operation, is defined and what information subsequent streams carry. The most comprehensive level of mineral processing models is the particle-based one which includes practically all necessary information on streams for modeling unit operations. Within this study, a particle-based unit operation model was built for wet low-intensity magnetic separation, and existing size classification and grinding models were evaluated to be used in particle level. A property-based model of magnetic beneficiation plant was created based on one of the LKAB operating plants in mineral and particle level and the results were compared. Two different feeds to the plant were used. The results revealed that in the particle level, the process model is more sensitive to changes in feed property than any other levels. Particle level is more capable for process optimization for different geometallurgical domains.

Crystal engineering has advanced the strategies of design and synthesis of organic solids with the main focus being on improving the properties of the developed materials. Research in this area has a significant impact on large-scale manufacturing as industrial processes may give rise, at various stages, to stress-induced transformations and product modification. This thesis investigates the solid-state properties at play in the case of the surface and structural reorganization which results from the stress within a crystal during the drying of labile multicomponent organic solids. Chapter 1 introduces various concepts in solid-state chemistry and explores their application in the manufacture of solid pharmaceuticals. The significance of stress-induced transformations during the drying process is illustrated by reactions associated with crystal decomposition processes such as dehydration, desolvation and sublimation. The chapter also introduces carbamazepine (CBZ) multicomponent materials as models for the studies of stress-induced transformations. Chapter 2 presents the experimental section of the work and describes the materials, methods and equipment used for the study. Chapter 3 presents the analysis of the various crystal structures of CBZ. The crystal forms are classified with an emphasis on a comparison of intermolecular interactions, coformer arrangement, crystal packing and the geometric parameters of slip/cleavage planes within the crystals. Chapter 4 details the experimental methods for preparation of the samples. Cooling solution crystallization was the standard method which has been selected, and crystal habit and surface variations have been studied as a function of the solution concentration and the crystallization environment. Attention is given, in particular, to the preparation of carbamazepine dihydrate and the specific cocrystals carbamazepine cocrystals formed with benzoquinone and oxalic acid. Chapter 5 is devoted to the dehydration of carbamazepine dihydrate for samples prepared and examined in approximate 1-gram laboratory scale quantities. It explores the effect of vacuum, temperature, humidity and seeding on the surface and bulk properties of the products. Chapter 6 presents the solid-state characterization results obtained for samples crystallized at a much larger scale (ca. kilogram quantities) with a particular emphasis placed on their mechanical properties. It explores the comparison of large scaled batches with laboratory scale samples in order to obtain a greater understanding of how small-scale laboratory studies may be extrapolated to more commercial processes. Chapter 7 present results on the stress-induced transformations of carbamazepine solvates and cocrystals. It details the effect of thermal decomposition on the surface and bulk properties of the products, possible seeding effects, and the interconversion between carbamazepine dihydrate and carbamazepine benzoquinone cocrystal. Chapter 8 combines the research findings concerning the structural analyses of the materials in the context of current literature. Limitations related to the use of carbamazepine as a model and to the experimental set-up are also explored. In the final chapter conclusions are presented which correlate observations made on the crystallization and decomposition of multicomponent materials operating at small-scale to effects appropriate to manufacturing of pharmaceuticals at large scale.

Ad hoc networks have gained significant importance and gathered huge momentum within the wireless network research community. We explore the novel idea of applying ad hoc networking for urban search and rescue operations. Several algorithms have been proposed and implemented for routing in ad hoc networks and their performance have been thoroughly analyzed. But none of the prior work deals specifically for search and rescue operations, which entail certain specific criteria such as prevention of node loss, maximizing the area of coverage and constant and instantaneous access to a main controller. In this thesis, we propose a centralized and adaptive algorithm tailored for efficient performance of mobile nodes assisting in search and rescue operations. The proposed algorithm assists in finding and maintaining stable links between the mobile nodes and base station, while optimizing the area of coverage and energy efficiency of the nodes. The algorithm is implemented using ns (network simulator), and its performance is compared with that of a widely used ad hoc routing protocol, Ad hoc On-demand Distance Vector (AODV) routing protocol. We use frequency of link breakages, network throughput and routing overhead as our performance metrics. This algorithm can also be extended to provide support for routing among mobile nodes.

Cellular immortalization is a major hallmark of cancer and is a multi-step process that requires numerous cell-type specific changes, including inactivation of control mechanisms and stabilization of telomere length. The telomeres at the chromosome ends are essential for genomic stability, and limit the growth potential of most cells. With each cell division, telomeres are shortened. Short telomeres may induce an irreversible growth arrest stage called senescence, or a growth crisis stage characterized by high genomic instability and cell death. Only very rarely do cells escape from crisis and become immortal, a stage that has been associated with the activation of the telomerase enzyme which can elongate and stabilize the telomeres. The processes leading to senescence bypass, growth crisis escape and finally immortalization are only beginning to be elucidated. Most of our knowledge of the immortalization process is based on analyses of human fibroblast and epithelial cell cultures immortalized by genetic modification. In this thesis, spontaneously immortalized human T lymphocytes derived from patients with Nijmegen Breakage Syndrome and a healthy individual were used to identify critical events for senescence bypass and immortalization. Genetic analysis showed a clonal progression and non-random genetic changes including the amplification of chromosomal region 2p13-21 as an early event in the immortalization process. Telomere length gradually shortened at increasing population doublings and growth crisis was associated with critically short telomeres. The clone(s) that escaped growth crisis demonstrated a logarithmic growth curve, very short telomeres and, notably, no increase in telomerase activity or expression of the telomerase catalytic gene, hTERT. Instead, upregulation of telomerase activity and telomere length stabilization were late events in T lymphocyte immortalization. Escape from crisis was associated with downregulation of DNA damage response genes and altered expression of cell cycle regulators and genes controlling the cellular senescence program. These data indicated that a number of layers of regulation are important in the process of immortalization and to provide further mechanistic detail, epigenetic analysis was carried out. Genome wide methylation array analysis identified early and step-wise methylation changes during the immortalization process. Interestingly, applying these findings to tumors of T cell origin revealed commonly methylated CpG sites in transformed cells. Deregulated gene expression of the polycomb complexes may have contributed to the epigenetic changes observed. Taken together, our analysis of spontaneously immortalized T cell cultures identified several steps in the immortalization process including genetic, epigenetic, gene expression and telomere/telomerase regulatory events, contributing further insights to the complexity of cancer cell immortalization.

The production of multi-component cement from clinker and two additives such as trass and blast furnace slag has now spread throughout the world. These additives are generally interground with clinker to produce a composite cement of specified surface area. The grinding stage is of great importance as it accounts for a major portion of the total energy consumed in cement production and also as it affects the quality of composite cements by the particle size distribution of the individual additives produced during grinding. This thesis study was undertaken to characterize the breakage properties of clinker and the additives trass and slag with the intention of delineating their grinding properties in separate and intergrinding modes. Single particle breakage tests were conducted by means of a drop weight tester in order to define an inherent grindability for the clinker and trass samples in terms of the median product size ( ). In addition, a back-calculation procedure was applied to obtain the breakage rate parameters ( ) of perfect mixing ball mill model using industrial data from a cement plant. Kinetic and locked-cycle grinding tests were performed in a standard Bond mill to determine breakage rates and distribution functions for clinker, trass and slag. Bond work indices of these cement components and of their binary and ternary mixtures were determined and compared. Attempts were made to use back-calculated grinding rate parameters to simulate the Bond grindability test. The self-similarity law was proved to be true for clinker and trass that their shapes of the self-similarity curves are unique to the feed material and independent of the grinding energy expended and overall fineness attained. The self-similar behaviour of tested materials will enable process engineers to get useful information about inherent grindability and energy consumption in any stage of the comminution process. The parameters, and indicating the degree of size reduction were defined with different theoretical approaches as a function of energy consumption by using single particle breakage test data of clinker and trass. The breakage distribution functions were found to be non-normalizable. On the other hand, the breakage rate functions were found to be constant with respect to time but variable with respect to changing composition in the Bond ball mill. These variations are critical in computer simulation of any test aiming to minimize the experimental efforts of the standard procedure. As a result of the back calculation of breakage rate parameters for clinker and trass samples in the Bond mill, no common pattern was seen for the variation of the rate parameters. Therefore, computer simulation of the Bond grindability test did not result in an accurate estimation of the Bond work index.

Size reduction processes, particularly fine grinding systems, in mineral processing and cement production plants constitute a great portion of energy consumption and operating costs. Therefore, the grinding systems should be designed properly and operated under optimum conditions to achieve productive and cost effective operations. The use of simulation based on kinetic mathematical models of grinding has proven useful in this respect. The kinetic models contain two essential parameters, namely, breakage rate and breakage distribution functions, that are to be determined experimentally, and preferably in laboratory, or by back-calculation from the mill product size distribution for a given feed size distribution. Experimental determination of the breakage parameters has been mostly carried out in laboratory batch mills using one-size-fraction material. The breakage rate parameter is obtained from the disappearance rate of this one-size-fraction material, while the breakage distribution parameters are estimated from the short-time grinding of the same material. Such laboratory methods using one-size fraction material, however, are not truly representative of industrial continuous mill operations where the mill contents have a distribution of particle sizes. There is evidence in the literature that the size distribution of the mill contents affects the breakage parameters. This thesis study was undertaken with the main purpose of investigating the effect of the size distribution of the mill hold-up on the brekage parameters of quartz and calcite minerals in lockedcycle dry grinding experiments. The locked-cycle and one-size-fraction experiments were performed in the Bond ball mill instrumented with a torque-measuring device. Different closing screen sizes were used in the locked-cycle work to produce different size distributions of the mill hold-up, and the operating conditions were changed in the one-size-fraction experiments to obtain different power draws. Particle breakage parameters were assessed for these changing conditions. Prior to the experiments related to the main purpose of the study, preliminary experiments were conducted for two reasons: (i) to find the power draw of the Bond mill in relation to the operating conditions with the intention of eliminating the use of costly torque-measuring devices by others / and (ii) to find the most accurate estimation method of breakage distribution functions among the three existing methods, namely, the &ldquo / zero-order production of fines&rdquo / method, the BII method, and the G-H method. The G-H method was found to be more appropriate for the current study. The locked-cycle grinding experiments revealed that the breakage rate function of coarse fractions increased with increasing proportion of fines in the mill hold-up. Breakage distribution functions were found to be environment-dependent and non-normalizable by size in one-size-fraction and locked cycle grinding experiments. It was concluded that the cumulative basis breakage rate function could sufficiently represent the breakage characteristics of the two studied materials in a wide range of operating conditions. Therefore, it would be more appropriate to evaluate the breakage characteristics of materials ground in ball mills by linearized form of the size-discretized batch grinding equation using single parameter instead of dealing with two parameters which may not be independent of each other.

The objective of this thesis is to investigate the principles of laboratory-scale particle bed comminution in a piston-die-press. The feed materials used in this investigation are quartz and calcite which were stage-crushed and dry screened to produce 3.35 x 2.36, 2.36 x 1.7, 1.7 x 1.18, 1.18 x 0.85, and minus 0.85mm size fractions. First, these narrow size fractions (excluding minus 0.85mm fraction) were comminuted under different pressures to determine the baseline for energy utilization. Then, these size fractions and minus 0.85mm size fraction were proportionately mixed to produce feeds of three different size distributions having three different Gates-Gaudin-Schuhmann (GGS) size distribution moduli (m=0.5, 0.7, and 0.9), and comminuted under different bed pressures of appropriate magnitudes to generate a reasonable range of specific breakage energy inputs. As a result of the experiments carried out, it can be concluded that higher amounts of fines were obtained from calcite samples than quartz at all narrow-range size fractions and distribution moduli. Furthermore, experimental results showed that the feed material having the widest size distribution (m = 0.5) showed more resistance to size reduction when compared with narrow-size fractions, which led to increase in energy consumption due to the presence of higher amounts of fines. Tests samples with distribution moduli of 0.7 and 0.9 showed higher resistance to size reduction than narrow-size samples, but the reduction ratios achieved with the size distributed samples were higher than those achieved with the narrow-size samples. In addition, by using t-curves (t50 and t10) the amounts of breakage of different samples were compared. Consequently, the distribution modulus of 0.9 gave better breakage results in terms of expended energy and amount of breakage than all narrow-size fractions, especially for the relatively soft mineral calcite.

The main objective in this study is to compare breakage parameters of narrow size fractions of cement clinker taken from the product end and feed end of industrial-scale high pressure grinding rolls (HPGR) in order to assess whether the breakage parameters of clinker broken in HPGR are improved or not. For this purpose, drop weight tests were applied to six narrow size fractions above 3.35 mm, and batch grinding tests were applied to three narrow size fractions below 3.35 mm. It was found that the breakage probabilities of coarse sizes and breakage rates in fine sizes were higher in the HPGR product. This indicated that clinker broken by HPGR contained weaker particles due to cracks and damage imparted. However, no significant weakening was observed for the -19.0+12.7 mm HPGR product. Although HPGR product was found to be weaker than HPGR feed, fragment size distribution of HPGR product did not seem to be finer than that of the HPGR feed at a given loading condition in either the drop weight test or batch grinding test. Also, drop weight tests on HPGR product and HPGR feed showed that the breakage distribution functions of coarse sizes depended on particle size and impact energy (J). Batch grinding tests showed that the specific breakage rates of HPGR product and HPGR feed were non-linear which could be represented with a fast initial breakage rate and a subsequent slow breakage rate. The fast breakage rates of each size fraction of HPGR product were higher than HPGR feed due to cracks induced in clinker by HPGR. However, subsequent slow breakage rates of HPGR product were close to those of HPGR feed due to elimination of cracks and disappearance of weaker particles. Besides, the variation in breakage rates of HPGR product and HPGR feed with ball size and particle size also showed an abnormal breakage zone where ball sizes were insufficient to effectively fracture the coarse particles. Breakage distribution functions of fine sizes of HPGR product and HPGR feed were non-normalizable and depended on particle size to be ground. However, batch grinding of -2.36+1.7 mm and -1.7+1.18 mm HPGR feed yielded the same breakage pattern.

Genome wide studies have uncovered the existence of large-scale copy number variation (CNV) in the human genome. The human genome of different individuals was initially estimated to be 99.9% similar, but population studies on CNV have revealed that it is 12-16% copy number variable. Abnormal genomic CNVs are frequently found in subtelomeres of patients with mental retardation (MR) and other neurological disorders. Rearrangements of chromosome subtelomeric regions represent a high proportion of cytogenetic abnormalities and account for approximately 30% of pathogenic CNVs. Although DNA double strand breaks (DSBs) are implicated as a major factor in chromosomal rearrangements, the causes of chromosome breakage in subtelomeric regions have not been elucidated. But due to the presence of repetitive sequences in subtelomeres, we hypothesized that chromosomal rearrangements in these regions are not stochastic but driven by specific sequence motifs. In a collaborative effort with Dr. Rudd (Department of human genetics at Emory University), we characterized subtelomeric breakpoints on different chromosome ends in search of common motifs that cause double-strand breaks. Using a yeast-based gross chromosomal rearrangement (GCR) system, we have identified a subtelomeric breakage motif from chromosome 2 (2q SBM) with a GCR rate that is 340 fold higher than background levels. To determine if the fragility of 2q SBM was driven by the formation of secondary structures, the helicase activities of Sgs1 and Pif1 were disrupted. These helicases have been shown to destabilize DNA secondary structures such as G-quadruplex structures. Disruption of these helicases augmented chromosomal rearrangements induced by 2q SBM, indicating that these helicases are required for maintenance of this sequence. We also donwregulated replication fork components to determine if 2q SBM was imposing any problems to the replication fork machinery. Downregulation of replication fork components increased chromosomal rearrangements, indicating that intact replication fork was a critical determinant of 2q SBM fragility. Using a yeast-based functional assay, these experiments have linked human subtelomeric repetitive sequences to chromosomal breakage that could give rise to human CNV in subtelomeric regions.

This study showed that hydrodynamic particle breakage had potential as a method to help improve the disinfection of wastewater effluents. The physicochemical properties of flocs from four distinct effluents sources (combined sewer overflow, settled combined sewer overflow, primary effluent, and final effluent) were compared before and after hydrodynamic treatment. The use of hydrodynamic force to cause floc breakage was shown to be effective, though variable, across all source types. This variation in floc breakage did not have a significant impact on the UV disinfection achieved, as the UV dose kinetics were similar across samples from the same source type. The results of this study demonstrate how the physicochemical properties of floc are affected when exposed to shear force. These observations further the understanding of floc composition and behaviour when shear forces are applied while also providing evidence to indicate this process improves the performance of UV disinfection technology.