Increasing Accuracy of Simulation Modeling via a Dynamic Modeling Approach

Simulating processes is a valuable tool which provides in-depth knowledge about overall performance of a system and caters valuable insight on improving processes. Current simulation models are developed and run based on the existing business and operations conditions at the time during which the simulation model is developed. Therefore a simulation run over one year will be based on operational and business conditions defined at the beginning of the run. The results of the simulation therefore are unrealistic, as the actual process will be going through dynamic changes during that given year. In essence the simulation model does not have the intelligence to modify itself based on the events occurring within the model. The paper presents a dynamic simulation modeling methodology which will reduce the variation between the simulation model results and actual system performance. The methodology will be based on developing a list of critical events in the simulation model that requires a decision. An expert system is created that allows a decision to be made for the critical event and then changes the simulation parameters. A dynamic simulation model is presented that updates itself based on the dynamics of the actual system to reflect correctly the impact of organization restructuring to overall organizational performance

An integrative and systems biology approach to Drosophila melanogaster transcriptomes

The availability of fully sequenced genomes of the model organisms including Drosophila, and their subsequent annotation has afforded seamless opportunities for reverse genetics in a complex model organism. With the advent of DNA microarrays to assay the levels of tens of thousands of genes in a single sample, functional genomics has been significantly aided to understand the functions in systems context. These microarrays have been employed predominantly on the RNA samples that are extracted from the whole animals for example at different developmental stages or in response to external stimuli. However, these approaches relied on the expression patterns that represent the sum of transcription coming from all the organs, which do not estimate the tissue-specificity of transcription. The purpose of this thesis is to provide tissue-specific transcriptomes of Drosophila melanogaster that were generated as part of the large FlyAtlas project using Affymetrix Drosophila GeneChips® (or microarrays). These chips, one at a time interrogate the levels of 18,500 transcripts (that represent all known genes) using 18,880 distinct probe sets in a single, total RNA sample. For each tissue, four biological replicates were analysed using the chips and the normalised signal intensities were obtained that represent the relative levels of mRNA expression. Using the transcriptomes, a general analysis was performed for potential novel insights into tissue-specific functions (Chintapalli et al., 2007) (Chapter 3). Then, a comparative analysis of epithelial tissues was performed to understand how the epithelia are organised in terms of their transcriptomes (Chapter 4). The Malpighian tubules are the Drosophila epithelial counterparts of the human kidney. They show asymmetric organisation in the body cavity. FlyAtlas segment-specific tubule transcriptomes allowed the comparison of their potential functional similarities and differences, thus to understand the asymmetry in function (Chapter 5)(Chintapalli, 2012). This identified a human Best vitelliform macular dystrophy (BVMD) disease homolog, Best2 in only the anterior pair of tubules that have the morphologically and functionally distinct enlarged initial (or distal) segment, a storage organ for Ca2+. Bestrophins were accordingly selected as candidate genes to analyse organismal functions, and thus to validate previous two theories that implicated bestrophins as Ca2+-activated Clˉ channels and/or Ca2+ channel regulators (Chapter 6). The confocal microscopy analysis of bestrophin YFP fusion proteins revealed interesting and novel localisations of bestrophins, in that Best1 was found in the apical plasma membranes, Best2 localised to peroxisomes, Best3 and Best4 were found intracellular. The salt survival analysis showed that Best1 is essential in regulating extra salt levels in the body. Furthermore, the fluid secretion analysis showed Best1’s potential role in Ca2+-dependent Clˉ function. Interestingly, the flies with reduced levels of Best2 expression showed increased ability to survive on extra salt food; the basis for this was investigated further in Chapter 7. Best2 was also found abundant in the eyes than anywhere else in the head. A comparative analysis of anterior tubule- and eye-specific transcriptomes revealed a potential overlap of Ca2+ signaling components, in that the PLCβ signaling was one. A neuropeptide Ca2+ agonist, capa1 evoked secondary cytosolic Ca2+ responses were found high in Best2 knockdowns. A quantitative PCR (qPCR) analysis of candidate Ca2+ signaling and homeostasis genes in Best2 mutants revealed their gene expression upregulation, under control-fed and salt-fed conditions than their wildtype controls, fed on similar diet regimes. The norpA that encodes PLCβ was found significantly enriched in the mutants. Cyp6a23 is another gene that was highly upregulated in Best2 mutants; it is a Drosophila homologue of human Cyp11b, a Ca2+-responsive gene implicated in renal salt wasting. Upon the downregulation of Cyp6a23, flies became sensitive to salt diet feeding. Other genes investigated and found to be upregulated in the mutants include transient-receptor-potential (trp) Ca2+ channel and retinal degeneration C (rdgC). Together, these results strongly suggest Best2 as a potential Ca2+ channel regulator, and provide fascinating insight into bestrophin function. Peroxisomal localisation of Best2 in line with the implication that peroxisomes act as dynamic regulators of cell Ca2+ homeostasis led to another aspect of the project (Chapter 8). This study identified two peroxins that are most abundant in the tubules and play essential roles in the novel cyclic nucleotide-regulated peroxisomal Ca2+ sequestration and transport pathway and that are detrimental for peroxisome biogenesis and proliferation

DESIGN AND EVALUATION OF FLUTAMIDE-LOADED POLYCAPROLACTONE NANOPARTICLES BY 23 FACTORIAL DESIGN AND NANOPRECIPITATION METHOD

Objective: The present work was aimed to prepare and evaluate polymeric nanoparticles (NPs) of flutamide by nanoprecipitation method and factorial. The influences of various formulation components such as polymer, organic phase volume, and surfactant on the characteristics of NPs were investigated.Methods: The polycaprolactone (PCL) loaded with drug was evaluated for surface morphology, surface charge, particles size, encapsulation efficiency, drug content, and in vitro release studies. Fourier transform infrared studies were indicated no interaction between the drug and polymer.Results: The results of the drug release study of NPs may fit with different kinetic equations. The particle size varied from 128 to 317 nm and zeta potential was in negative and its value found to be - 46.4 mv. The content of flutamide was found in between 74%±0.72 to 92%±0.53 in flutamide loaded PCL NPs. The minimum and maximum entrapment efficiencies were found to be of 75%±0.66 and 92%±0.70. The percentage yields of all formulations were in the range of 46.05%±1.56–86.78%±1.32. The in vitro drug release followed zero order with sustained behavior for a period of 24 h. Results of accelerated storage conditions of optimized formulation revealed that no significant changes in formulation F2.Conclusion: The present investigation opens new frontiers in developing flutamide NPs for targeting delivery to the prostate for the prostate cancer treatment which also overcome the problems associated with conventional formulations such as multiple-dose therapy, poor patient compliance, and high treatment cost

Dispersion, Self-assembly, And Rheological Characterization of Dna-complexed Boron Nitride Nanosystems

Stable liquid dispersions and the subsequent self-assembly of boron nitride (BN) nanostructures are a vital precursor for translating their exceptional electrical, mechanical, thermal, and optical properties into large-area assemblies with controlled properties. However, achieving individually dispersed BN nanomaterials including BN nanotubes (BNNTs) and hexagonal BN nanosheets (hBN) in almost any solvent has been hindered by strong van der Waals interactions among nanomaterials. In this dissertation work, we reported a comprehensive study on developing an efficient dispersion, self-assembly, and rheological characterization of BN nanomaterials. Particularly, we reported a highly efficient dispersions of BNNTs through noncovalent complexation while exploiting the solvent-nanotube-dispersant interactions using biopolymer DNA and various solvents including water and alcohol. The subsequent purification by membrane filtration revealed that the raw BNNT material constitutes ~ 45.2 mass % of non-nanotube impurities. Ofthe alcohols tested, isopropyl alcohol (IPA) was found to be an efficient solvent, resulting in a dispersion yield of as high as ~ 48 % nanotubes in an IPA/water mixture with 60 vol % IPA by mild bath sonication. Molecular dynamics simulations further revealed that IPA played a pseudosurfactant role in solvating BNNTs by replacing water molecules in the solvation layer while IPA is added. The dispersion techniques developed for BNNTs has been extended for aqueous dispersions of v hBN as well. Additionally, we demonstrated the formation of solid BNNT films comprised of spontaneously aligned nanotubes through drop drying of DNA-wrapped BNNTs. The overall properties of solid BNNT assemblies are directly influenced by the physical properties of nanotubes, including the tube lengths. Conventional surface deposition method by imaging dried samples on a substrate revealed inconsistencies in the average lengths of the parent BNNTs coated by DNA and SDC, due to the differential binding of DNA-BNNTs to a substrate. Therefore, we determined the nanotube lengths using an alternative method - rheological characterization - by measuring the viscosity of dilute dispersions of DNA-BNNTs, highlighting the Brownian rigid rod behavior of BNNTs. Combined, our study on the dispersion, self-assembly and rheology of BN nanomaterials paved a way for producing BN assemblies with controlled properties while offering green chemistry and multifunctionality

Performance evaluation of Mg-AgCI batteries for underwater propulsion

Magnesium-silver chloride seawater activated reserve pile-type battery was exclusively used in all underwater vehicles as a source of power due to its high energy density and power density. Various tests have been conducted on fully assembled battery to test its performance, suitability and compatibility. However, it is also essential that the battery is subjected to failure mode studies to understand the limitations of the battery and to analyse the vehicles performance under such situations. Various possible failure modes that the battery might experience during its usage as propulsion source in the underwater vehicle are identified, and the performance evaluation of scale9 down model (I O-cell module) of the battery has been carried out in the laboratory. The results are discussed to understand the electrochemical system and its effect on the overall performance of the vehicle. It has been observed that while some failure modes were found to affect the vehicles' performance adversely, only some failure modes are detrimental to the vehicle's performance

A Study of the Structure of Shear Turbulence in Free Surface Flows

Turbulence is a familiar phenomenon which gives rise to complicated problems in many branches of engineering. Hinze has set forth the following definition for turbulence: Turbulent fluid motion is an irregular condition of flow in which the various quantities show a random variation in time pnd space coordinates, so that statistically distinct average values can be discerned. Osborne Reynolds (1894) was the first to introduce the notion of statistical mean values into the study of turbulence. He visualized turbulent flow as the sum of mean and eddying motion. By introducing this sum of mean velocity and fluctuating velocity into the Navier-Stokes equations and with the aid of the continuity equation, he derived equations giving relationships between the various components of the fluctuating velocity. It was soon realized that before any further results could be obtained from a theoretical analysis of Reynold;s equations of motion, a mechanism had to be postulated for the ihteraction of fluctuating v~locity components at different points in the turbulent field. Consequently, three decades after Reynold\u27s: work, phenomenological theories of turbulence, such as the momentum-transfer theory of Prandtl (1926), the vorticity transport theory of Taylor (1932) and the similarity theory of Karman (1930) were introduced. Not only are they based on unrealistic physical models, but they do not furnish any information beyond temporal-mean velocity distribution. A complete theory of turbulence should describe the mechanism of production of turbulence, its convection, diffusion, distribution, and eventual dissipation for any given boundary conditions

Trends in Cardiac Pacemaker Batteries

Batteries used in Implantable cardiac pacemakers-present unique challenges to their developers and manufacturers in terms of high levels of safety and reliability. In addition, the batteries must have longevity to avoid frequent replacements. Technological advances in leads/electrodes have reduced energy requirements by two orders of magnitude. Micro-electronics advances sharply reduce internal current drain concurrently decreasing size and increasing functionality, reliability, and longevity. It is reported that about 600,000 pacemakers are implanted each year worldwide and the total number of people with various types of implanted pacemaker has already crossed 3 million. A cardiac pacemaker uses half of its battery power for cardiac stimulation and the other half for housekeeping tasks such as monitoring and data logging. The first implanted cardiac pacemaker used nickel-cadmium rechargeable battery, later on zinc-mercury battery was developed and used which lasted for over 2 years. Lithium iodine battery invented and used by Wilson Greatbatch and his team in 1972 made the real impact to implantable cardiac pacemakers. This battery lasts for about 10 years and even today is the power source for many manufacturers of cardiac pacemakers. This paper briefly reviews various developments of battery technologies since the inception of cardiac pacemaker and presents the alternative to lithium iodine battery for the near future

Implementation of Impulse Noise Reduction Method to Color Images using Fuzzy Logic

Image Processing is a technique to enhance raw images received from cameras/sensors placed on satellites, space probes and aircrafts or pictures taken in normal day-to-day life for various applications. Impulse noise reduction method is one of the critical techniques to reduce the noise in color images. In this paper the impulse noise reduction method for color images by using Fuzzy Logic is implemented. Generally Grayscale algorithm is used to filter the impulse noise in corrupted color images by separate the each color component or using a vector-based approach where each pixel is considered as a single vector. In this paper the concepts of Fuzzy logic has been used in order to distinguish between noise and image characters and filter only the corrupted pixels while preserving the color and the edge sharpness. Due to this a good noise reduction performance is achieved. The main difference between this method and other classical noise reduction methods is that the color information is taken into account to develop a better impulse noise detection a noise reduction that filters only the corrupted pixels while preserving the color and the edge sharpness. The Fuzzy based impulse noise reduction method is implemented on set of selected images and the obtained results are presented

Exosomal derived HLA-B-Associated Transcript-3 is a ligand for NKp30 and regulates Natural Killer Function in Innate and Adaptive Immune Responses

Natural Killer cells are key effector cells of the innate immune system. They were originally described as the first line of defense against infections and tumor cells that secrete cytokines and kill target cells without prior antigen stimulation. Emerging evidence reveals that NK cell activation is a more complex process and includes priming of NK cells that in turn shape the adaptive immune response mainly by interacting with dendritic cells. The activity of NK-cells is mainly mediated through their wide variety of receptors, activating and inhibitory in function. Among the versatile receptors present on NK cells, the activating receptor NCR3, NKp30 is a major receptor involved in both direct killing of target cells and mutual NK and dendritic cell activation. However, the cellular ligands on tumor-transformed cells and DCs have remained elusive. This study identifies HLA-B-associated transcript 3 (BAT3), as a tumor-associated cellular ligand for NKp30 and moreover it is shown that BAT3 is expressed in immature dendritic cells and released as exosomes into the extracellular environment. Further it demonstrates that BAT3 is expressed on the surface of exosomes either derived from tumor cells or iDCs activate NK cells resulting in a strong release of major cytokines (TNFα and IFNγ) and enhanced cytotoxicity. Moreover, BAT3 regulates the NK cell-mediated cytotoxicity against iDCs. Thus, a novel concept is proposed for target cell recognition by NK cells beyond "missing-self" and "induced-self", mediated through extracellular factors. These factors may be derived from the target cells as well from the accessory cells. Moreover, these data also suggest that the reciprocal activation of NK cells and iDCs is partly due to BAT3 presenting exosomes independent from direct cell contacts

Research and development of Co and Rh-promoted alkali-modified molybdenum sulfide catalysts for higher alcohols synthesis from synthesis gas

The demand for mixed alcohols has grown since ether compounds were banned as gasoline octane improvers in North America. Molybdenum-based catalysts in sulfide form are an attractive catalyst system for the conversion of synthesis gas to alcohols, due to their excellent resistance to sulfur poisoning and high activity for the water-gas shift reaction. The higher alcohols activity over these catalysts is low, due to the formation of hydrocarbons and CO2. Although a number of catalysts have been developed for this purpose, not any are used commercially at this time. The main objective of this Ph.D. research is to develop a catalyst system that is capable of selectively producing higher alcohols, particularly ethyl alcohols from synthesis gas. In the present series of studies, the investigation of an alkali-promoted trimetallic Co-Rh-Mo catalyst system has led to improvements in product stream composition. The effect of different loadings of active metal (Mo), alkali (K) promoter, and metal promoters (Co and Rh) on higher alcohol synthesis from synthesis gas were investigated using commercially available multi-walled carbon nanotubes (MWCNTs) as the catalyst support. The role of support on higher alcohols synthesis was also studied using different supports, such as ã-Al2O3, activated carbons with different textural characteristics, and MWCNTs. The catalysts were prepared using the incipient wetness impregnation method and extensively characterized in both oxide and sulfide phases using different techniques. Transmission electron microscopy (TEM) results revealed that the metal particles were uniformly distributed inside and outside of the carbon nanotubes, and that metal dispersions were higher on the alkali-promoted trimetallic catalyst supported on MWCNTs. The existence of promoted and un-promoted MoS2 sites was confirmed by diffuse reflectance infrared fourier transform spectroscopy (DRIFTS) studies of adsorbed CO over sulfided catalysts. Temperature programmed reduction (TPR) tests showed that the addition of metal promoters improved the reduction behaviour of the catalysts. XRD patterns showed that alkali-promoted catalysts were less crystalline compared to that of the catalyst not promoted with K. The formation of Co (Rh)-Mo-S species was evident in the XANES spectra of bimetallic and trimetallic alkali-promoted MoS2 catalysts. The activity and selectivity of the catalysts were assessed in a fixed-bed micro-reactor using temperature, pressure, and gas hourly space velocity in the ranges of 275 to 350°C, 800 to 1400 psig (5.52–9.65 Mpa), and 2.4 to 4.2 m3 (STP)/(kg of cat.)/h, respectively. The Ni-promoted catalyst showed higher activity towards the formation of hydrocarbons over that of alcohols. The total alcohols space time yield (STY) and higher alcohols selectivities are significantly higher over the activated carbon-supported catalysts compared to those supported on alumina. With increased content of K, the formation of alcohols increased and hydrocarbons formation rate was suppressed. The total alcohols STY increased with increased Co content over the Co-promoted MoS2-K/MWCNTs catalysts, whereas, the maximum ethyl alcohol and higher alcohols selectivities were observed on the catalyst promoted with 4.5 wt % Co. Over the Rh-promoted MoS2-K/MWCNTs catalysts, the maximum total alcohol yield, ethanol selectivity, and higher alcohols selectivity were observed on the catalyst with 1.5 wt % Rh. The MWCNT-supported alkali-promoted trimetallic catalyst with 9 wt % K, 4.5 wt % Co, 1.5 wt % Rh, and 15 wt % Mo showed the maximum higher alcohols STY and selectivity compared to other catalysts investigated. The textural properties of the support, such as average pore diameter, pore volume and surface area, could significantly influence the extent of reduction, morphology, adsorption and has direct influence on the synthesis of mixed alcohols from synthesis gas. The optimum higher alcohols STY and selectivity were obtained over the Co-Rh-Mo-K/MWCNT catalyst at 330°C, 1320 psi (9.1 Mpa), 3.8 m3 (STP)/(kg of cat./h) using a H2 to CO molar ratio value of 1.25. To predict the reaction rate for higher alcohols synthesis, the power law model was used for the reaction between CO and H2 on the catalyst surface and the data of this study are well fitted by the model. The activation energies of ethanol and higher alcohols obtained over Co-Rh-Mo-K/MWCNTs were low compared to those values reported in the literature. The sulfided alkali-promoted trimetallic Co-Rh-Mo catalyst supported on MWCNTs was stable over a period of 720 h of continuous reaction