Applying engineering principles to the design and construction of transcriptional devices

Thesis (Ph. D.)--Massachusetts Institute of Technology, Biological Engineering Division, 2008.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.Includes bibliographical references (leaves 180-203).The aim of this thesis is to consider how fundamental engineering principles might best be applied to the design and construction of engineered biological systems. I begin by applying these principles to a key application area of synthetic biology: metabolic engineering. Abstraction is used to compile a desired system function, reprogramming bacterial odor, to devices with human-defined function, then to biological parts, and finally to genetic sequences. Standardization is used to make the process of engineering a multi-component system easier. I then focus on devices that implement digital information processing through transcriptional regulation in Escherichia coli. For simplicity, I limit the discussion to a particular type of device, a transcriptional inverter, although much of the work applies to other devices as well. First, I discuss basic issues in transcriptional inverter design. Identification of key metrics for evaluating the quality of a static device behavior allows informed device design that optimizes digital performance. Second, I address the issue of ensuring that transcriptional devices work in combination by presenting a framework for developing standards for functional composition. The framework relies on additional measures of device performance, such as error rate and the operational demand the device places on the cellular chassis, in order to proscribe standard device signal thresholds. Third, I develop an experimental, proof-of-principle implementation of a transcriptional inverter based on a synthetic transcription factor derived from a zinc finger DNA binding domain and a leucine zipper dimerization domain. Zinc fingers and leucine zippers offer a potential scalable solution to the challenge of building libraries of transcription-based logic devices for arbitrary information processing in cells.(cont.) Finally, I extend the principle of physical composition standards from parts and devices to the vectors that propagate those parts and devices. The new vectors support the assembly of biological systems. Taken together, the work helps to advance the transformation of biological system design from an ad hoc, artisanal craft to a more predictable, engineering discipline.by Reshma P. Shetty.Ph.D

PHYTOCHEMICAL PROFILES OF THREE TRADITIONAL MEDICINAL PLANTS AND ITS ANTIMICROBIAL ACTIVITIES

Objective: The objective of the current study was to compare the phytochemical composition and to evaluate the antibacterial properties of Cissus qudrangularis, Cinnamomum zeylanicum and Trigonella foenum-graecum against the bacterial strains Escherichia coli and Bacillus circulans. Methods: Qualitative analysis and quantitative estimation of various phytochemical components were done using standard protocols. Antibacterial activity against gram-negative Escherichia coli and gram-positive Bacillus circulans was evaluated using standard protocol of agar well diffusion and disc diffusion assay. The zone of inhibition was calculated. Results: Preliminary phytochemical analysis showed the presence of alkaloids, saponins and tannins in all three plant extracts. In quantitative estimation, Cinnamomum zeylanicum showed high alkaloid content (22%), Cissus qudrangularis showed high saponin content (6%) Trigonella foenum-graecum showed a high concentration (4.65 mg/g) of tannin. All the three plants showed moderate antimicrobial activity. The water extract of Cinnamomum zeylanicum showed the highest zone of inhibition (13 mm) against Escherichia coli and the water extract of Trigonella foenum-graecum showed the highest zone of inhibition (11 mm) against Bacillus circulans. Conclusion: The result of this study supports the use of all the selected three medicinal plants as a source of antibacterial substance for the possible treatment of human pathogenic organisms. These plants can be further subjected to isolation of the therapeutic phytochemicals and further pharmacological evaluation

Mining Data Streams using Option Trees

Many organizations today have more than very large databases. The databases also grow without limit at a rate of several million records per day. Data streams are ubiquitous and have become an important research topic in the last two decades. Mining these continuous data streams brings unique opportunities, but also new challenges. For their predictive nonparametric analysis, Hoeffding-based trees are often a method of choice, which offers a possibility of any-time predictions. Although one of their main problems is the delay in learning progress due to the presence of equally discriminative attributes. Options are a natural way to deal with this problem. In this paper, Option trees which build upon regular trees is presented by adding splitting options in the internal nodes to improve accuracy, stability and reduce ambiguity. Adaptive Hoeffding option tree algorithm is reviewed and results based on accuracy and processing speed of algorithm under various memory limits is presented. The accuracy of Hoeffding Option tree is compared with Hoeffding trees and adaptive Hoeffding  option tree under circumstantial conditions. Keywords: data stream, hoeffding trees, option trees, adaptive hoeffding option trees, large database

Historical events and supply chain disruption : chemical, biological, radiological and cyber events

Thesis (M. Eng. in Logistics)--Massachusetts Institute of Technology, Engineering Systems Division, 2003.Includes bibliographical references (leaves 98-113).In the wake of the attacks of September 11, 2001, terrorism emerged as a legitimate threat not just to society, but to corporations as well. This new threat has challenged old business rules and prompted companies to rethink their supply chain operations. However, the events of September 11th were not the first or the only disruptions that the business world had experienced. This thesis reviews past historical events that simulate the effects of a terrorist attack and extracts lessons that can be applied by today's corporations to prepare for future attacks or disruptions. The types of events studied include Biological, Chemical, Radiological and Cyber disruptions. Through the analysis and synthesis of each event's impact, the following generalized recommendations emerged: Prior warnings and events should be acknowledged, studied and utilized. Government intervention may strain operations under disruptive stress. Alternate sourcing should be considered to ease supply issues. Disruptions should be approached in a comprehensive and forthright manner. A security and safety culture should be fostered to prevent disruptions and control their spread. Systems should be prepared to quickly operate in isolation during a disruption. Finally, impact is frequently less severe then initially predicted. Through the events described and these recommendations, this thesis aims to provide lessons for firms to manage their supply chains through future disruptions.by Reshma P. Lensing.M.Eng.in Logistic

PHYSICOCHEMICAL CHARACTERIZATION AND HEPATOPROTECTIVE ACTIVITY OF MANDUR BHASMA

Objective: Bhasmas are traditional Indian medicinal preparations that are standardized using quality control tests prescribed by Ayurveda and other guidelines. There is a need to study the adequacy of the existing quality control tests and to correlate these to the performance of the product. No attempt has been made in the literature to study the adequacy of these tests in determining the biological activity of a product and to suggests new analytical techniques for determining the quality. In the present work, an attempt has been made to compare marketed samples of Mandur bhasma with respect to various existing quality control tests and to analyze these samples using modern analytical techniques for the complete analysis of Mandur Bhasma. Adequacy of all the tests and techniques was studied with respect to the hepatoprotective activity of mandur bhasma in paracetamol induced hepatotoxicity in rats.Methods: The marketed products of three leading brands of Mandur Bhasma were analyzed for quality-control tests as prescribed by Ayurveda and other guidelines. These samples were also analysed using modern analytical techniques like AAS, IR, XRD, HPTLC, SEM. These formulations were then evaluated for their hepatoprotective activity in paracetamol induced hepatotoxicity in rats and the results obtained were correlated with analytical results.Results: It was found that all the three bhasma samples were passing in quality control tests as prescribed by Ayurveda and other guidelines. These samples produced similar results when analyzed using AAS and IR. The results were different when analyzed using colorimetry, HPTLC, SEM and XRD. The extent of hepatoprotection in rats with paracetamol induced hepatotoxicity was also found to be different in the three samples.Conclusion: The analysis was carried out on three different marketed samples, and a correlation has been reported. It was seen that although all the three formulations passed traditional quality control tests and the tests laid by regulatory guidelines, but still there were significant differences in their biological activity. Analysis of iron content using colorimetric method was found to be discriminating in estimating the biologically effective form of iron. It was also found that HPTLC, XRD and SEM should be further developed and validated as analytical tools in determining the quality of Mandur bhasma product.Keywords: Mandur bhasma, Colorimetry, IR, AAS, SEM, XRD, HPTLC, Hepatoprotective activit

Smart Approach for Public Transport

This paper is to provide public a Smart Assistance in Public Transport System. The paper is to be implemented for public bus (for PMTs in Pune). It has the entire smart assistance system required for public security and safety. The smart system includes safety form rash driving as well. It has accident detection and monitoring facility. It also has user friendly application for user to track bus on smart their phones. The smart system designed has both online (GPS) and offline (GSM) for user friendly service. It allows user to save its time by acknowledging no. of persons present in the bus as well as no. of seats available in the bus along with the current and next stop acknowledgment with its arrival timings. It also has ramp facility for handicap people. The system also many additions feature to make public transport system an intelligent and easy to use system so that public can take smart advantage of it. The system is specially designed for Smart Cities as it\u27s the recent development plan

Neural Network System Identification and Controlling of Multivariable System

Most of the industrial processes are multivariable in nature. Here Greenhouse system is considered which is the important application in agricultural process. Greenhouse is to improve the environmental conditions in which plants are grown .In this paper we have proposed identification of greenhouse system using input and output data sets to estimate the best model and validate the model. For MIMO systems, Neural Network System identification provides a better alternative to find their system transfer function. The results were analyzed and the model is obtained. From this obtained model ,the system is controlled by conventional method. By these method we can identify the model and control the complicated systems like Greenhouse