Vector Engineering for Cell and Gene Therapy

Progress in gene therapy has been hampered by the absence of a suitable delivery vector that is both easy to produce and delivers genetic payloads efficiently and specifically to the targeted disease cells. Cell-targeting proteins, primarily monoclonal antibodies, already exist in abundance but there is currently no robust and reproducibly effective way to functionalize viral vectors with these proteins. In the case of antibodies, non-covalent approaches to incorporate antibody onto a lentivirus surface leaves the linkage vulnerable to interference from serum immunoglobulins in immune-competent individuals. This dissertation focuses on enabling facile reprogramming of lentiviral vectors to deliver genetic payloads to specific cell types through in vitro covalent functionalization with cell-binding proteins. Two covalent-bond forming protein-protein pairs were explored to conjugate a HER2-binding protein to lentivirus pseudotyped with a binding-deficient, fusion-competent Sindbis virus envelope protein. Both the strategies resulted in functionalization of lentivirus and the titers were significantly higher compared to the naked virus. A receptor dependent retargeting was observed with functionalized virions. Lastly, the covalent bond was observed to be stable during prolonged dialysis and in presence of serum complement. A chemical conjugation approach was successfully exploited to functionalize the virions with an antibody fragment. In another project, we aim to develop a new platform technology, building upon the antibody-guided chicken vaccine technology and the single emulsion technology, for iii the discovery of chicken IgY antibodies against target cancer antigens. The antibody-guided chicken vaccine technology approach was successfully developed to generate an immune response in chickens against the target cancer antigen

Generation of tunable, high repetition rate optical frequency combs using on-chip silicon modulators

We experimentally demonstrate tunable, highly-stable frequency combs with high repetition-rates using a single, charge injection based silicon PN modulator. In this work, we demonstrate combs in the C-band with over 8 lines in a 20-dB bandwidth. We demonstrate continuous tuning of the center frequency in the C-band and tuning of the repetition-rate from 7.5GHz to 12.5GHz. We also demonstrate through simulations the potential for bandwidth scaling using an optimized silicon PIN modulator. We find that, the time varying free carrier absorption due to carrier injection, an undesirable effect in data modulators, assists here in enhancing flatness in the generated combs.Comment: 10 pages, 7 figure

InnovFaceNet: Deep Face Recognition for Industrial Environments

In recent times the usage of intelligent systems have paved way formany applications to be robust and self-reliant. One such popularand vast growing technology is face recognition. Facial Recognitiontechnology is used in security, surveillance, criminal justice systemsand many other multimedia platforms. This work proposes a realtime facial recognition technology which can be used in any industrialsetup eliminating manual supervision, ensuring authorized accessto the personnel in the plant. Due to the recent development ofCOVID-19 pandemic around the world, wearing masks has becomea necessity. Our proposed facial recognition technology identifies aperson’s face with mask or no mask in real time with a speed of20 FPS on a CPU and an F1-score of 95.07%. This makes ouralgorithm fast, secure, robust and deployable on a simple personalcomputer or any edge device at any industrial plant or organization

A service to automate the task assignment process in YAWL

Master of ScienceDepartment of Computing and Information SciencesGurdip SinghDeveloping an optimal working environment and managing the of work load in an efficient manner are the major challenges for most businesses today. So, the importance of the workflow and workflow management in an organization is unquestionable. Many organizations use sophisticated systems to organize the workflows. One such workflow system based on a concise and powerful modeling language called “Yet Another Workflow Language” is YAWL. YAWL handles complex data, transformations, integration with organizational resources and Web Service integration. Workflow comprises of three main perspectives: control-flow, data and the resources. In Yawl, the control-flow and the data-flow are tightly coupled within the workflow enactment engine. But the resource perspective is provided by a discrete custom service called Resource Service. Administrative tools are provided using which the administrator has to manually select the resource (referred as participant) which needs to perform a particular task of the workflow. This project aims at developing a service which can automate the assignment of the tasks to the participants by using the Resource service which provides number of interfaces that expose the full functionality of the service. The application of this project with respect to Healthcare domain is presented. Healthcare domain is the one of the most demanding and yet critical business process. Hospitals face increasing pressure to both improve the quality of the services delivered to patients and to reduce costs .Hence there is significant demand on hospitals in regard to how the organization, execution, and monitoring of work processes is performed. Workflow Management Systems like YAWL offers a potential solution as they support processes by managing the flow of work

ImageSubXSS: an image substitute technique to prevent Cross-Site Scripting attacks

Cross-Site Scripting (XSS) is one of serious web application attack. Web applications are involved in every activity of human life. JavaScript plays a major role in these web applications. In XSS attacks hacker inject malicious JavaScript into a trusted web application, execution of that malicious script may steal sensitive information from the user. Previous solutions to prevent XSS attacks require a lot of effort to integrate into existing web applications, some solutions works at client-side and some solutions works based on filter list which needs to be updated regularly. In this paper, we propose an Image Substitute technique (ImageSubXSS) to prevent Cross-Site Scripting attacks which works at the server-side. The proposed solution is implemented and evaluated on a number of XSS attacks. With a single line, developers can integrate ImageSubXSS into their applications and the proposed solution is able to prevent XSS attacks effectively

An Efficient Movie Recommender Engine: Application of Artificial Intelligence

A recommendation system is a system that provides suggestions to users for certain resources likebooks, movies, songs, etc., based on some data set. Movie recommendation systems usually predictwhat movies a user will like based on the attributes present in previously liked movies. Suchrecommendation systems are beneficial for organizations that collect data from large amounts ofcustomers and wish to effectively provide the best suggestions possible. A lot of factors can beconsidered while designing a movie recommendation system like the genre of the movie, actorspresent in it or even the director of the movie. The systems can recommend movies based on one or acombination of two or more attributes. In this paper, the recommendation system has been built on the type of genres that the user might prefer to watch. The approach adopted to do so is content-based filtering using genre correlation. The dataset used for the system is Movie Lens dataset

Training Set Design for Test Removal Classication in IC Test

This thesis reports the performance of a simple classifier as a function of its training data set. The classifier is used to remove analog tests and is named the Test Removal Classifier (TRC). The thesis proposes seven different training data set designs that vary by the number of wafers in the data set, the source of the wafers and the replacement scheme of the wafers. The training data set size ranges from a single wafer to a maximum of five wafers. Three of the training data sets include wafers from the Lot Under Test (LUT). The training wafers in the data set are either fixed across all lots, partially replaced by wafers from the new LUT or fully replaced by wafers from the new LUT. The TRC\u27s training is based on rank correlation and selects a subset of tests that may be bypassed. After training, the TRC identifies the dies that bypass the selected tests. The TRC\u27s performance is measured by the reduction in over-testing and the number of test escapes after testing is completed. The comparison of the different training data sets on the TRC\u27s performance is evaluated using production data for a mixed-signal integrated circuit. The results show that the TRC\u27s performance is controlled by a single parameter- the rank correlation threshold

Kinetics of Reaction of Benzyl Chloride with H2S-Rich Aqueous Monoethanolamine Under Liquid-Liquid-Liquid Phase-Transfer Catalysis

This thesis work engages the study of treatment of hydrogen sulphide gas based on phase transfer catalysis for the production of DiBenzyl Sulphide and other organic sulphides at room temperature and optimizing the conditions for 100% selectivity and maximum conversion. This study focuses on the condition optimization for preparation of Dibenzyl sulphide and also maximum absorption of H2S on cheaper solvents. Benzyl chloride was used as the reactant and MethylEthylAmine (MEA) for absorption of H2S gas. Phase transfer catalyst chosen was PEG-400 for its non-pollutant nature and cost of course. Toluene was made the organic Solvent. The amount of catalyst required was around 0.12wt% because of its low reactivity. The optimum time was around 7-8 hrs and the sulphide concentration for DBS formation was 1.646 kmol/m3 at a temperature of 60ºC. The experiments were done using one variable at a time approach as it was a simple system

The Functionalization of Single-Walled Carbon Nanotubes with Biomolecules to Target Professional Phagocytes and Promote Biodegradation

Aggressive penetration of nanomaterials in different spheres of our life - from novel technologies to a plethora of consumer products, raises concerns about their possible adverse effects on public health. Several studies report that nanotubes cause lung toxicity. With increase in day-to-day applications of carbon nanotubes, particulate exposure either under occupational or environmental settings is inevitable. In the classic inflammatory response to nanotubes, emigration of neutrophils (PMNs) followed by macrophages into sites of particle deposition has been observed. The major role of the cells is to phagocytoze and promotes particulate clearance and the clearance might be essentially dependent on effective recognition. Carbon nanotubes are not effectively recognized by professional phagocytes and delayed clearance of particles within the lung parenchyma can thus be majorly attributed to impaired phagocytosis or deficiency in components involving their effective degradation. We in our research coated nanotubes with biomolecules to promote recognition, uptake and biodegradation by professional phagocytes. Coating nanotubes with "eat-me"-phospholipid signal, phosphatidylserine proved to be an effective strategy for targeting particles to professional phagocytes, specifically macrophages both in vitro and in vivo. However, opsonization of nanotubes made them competent for both macrophages and neutrophils. This targeting also enhanced the biodegradation in neutrophils and to a lesser extent in macrophages via action of myeloperoxidase and its potent oxidants whose critical role in biodegradation was delineated in cell free based in vitro studies. Further, in vivo experiments using wild type and myeloperoxidase null mice showed a significantly lower degree of biodegradation and particle elimination in latter animal type, underscoring the role of neutrophil peroxidase in biodegrading carbon nanotubes. Using contemporary techniques- confocal, transmission and scanning electron microscopy, Vis-NIR and Raman spectroscopy, we evaluated the hypothesis. Taken together, the results from the doctoral work suggest that targeting of nanotubes to professional phagocytes can be achieved by coating with certain biomolecules and this targeting can reduce the biopersistence and inflammation associated due to the presence of otherwise relatively biodurable nanotubes in biological ambience. The dissertation also foresees functionalization of nanotubes as a strategy to combat potential toxic effects of nanotubes which pose potential risk to the public health

One Pulmonary Lesion, 2 Synchronous Malignancies

Introduction. Mantle cell lymphoma (MCL) comprises approximately 3% to 10% of all non-Hodgkin lymphomas. Although there is an increased risk for secondary malignancies after treatment among non-Hodgkin lymphomas survivors, a synchronous diagnosis of primary lung cancer arising in conjunction with lymphoma at the same site has rarely been reported. We report an unusual case of primary lung adenocarcinoma with coexistent MCL within the same lung lesion. Case Presentation. A 55-year-old female with newly diagnosed stage IV-B MCL was referred for workup of a right upper lobe cavitary lesion detected during lymphoma staging. A whole-body positron-emission tomography-computed tomography scan revealed diffuse adenopathy but also identified a cavitary right upper lobe lesion atypical for lymphoma. Bronchoscopy was unremarkable with cytology (on lavage) negative for malignancy. At 2 months, a computed tomography scan of the chest showed a persistent lesion. A video-assisted thoracoscopic wedge resection was performed. Histopathological examination revealed a lepidic predominant, well-differentiated adenocarcinoma (stage T1a) and foci of lymphoid infiltrate within and adjacent to the adenocarcinoma consistent with lung involvement by MCL. Discussion. Synchronous presentation of primary lung adenocarcinoma and lymphoma at a single site is exceedingly rare. Nonresolving pulmonary lesions with features atypical for lymphoma should be viewed with caution and worked up comprehensively to rule out occult second malignancies, in order to guide a prompt diagnosis and appropriate treatment