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Biological Engineering - Master's degree

Mostrando recursos 1 - 20 de 91

  1. Computational modeling and simulation for projectile impact and indentation of biological tissues and polymers

    Geiser, Kyle
    Understanding the elastic and viscoelastic responses of biological soft tissues and engineered polymer simulants is of great interest to predicting and preventing penetrative injuries. Detailed understanding of the mechanical processes at work could aid in the development and evaluation of protective strategies such as armor and helmets, and repair strategies including robotic surgery or needle-based drug delivery. However, due to the mechanical complexity of so-called "soft tissues," including nonlinear viscoelastic behavior, surface adhesion, material failures and shock effects, the experimental characterization of various soft tissues is challenging and individual mechanical processes are often impossible to decouple without computational models and...

  2. Integration of metabolic modelling with machine learning to identify mechanisms underlying antibiotic killing

    Wright, Sarah Natalie
    Microbial pathogens are becoming a pressing global health issue due to the rapid appearance of resistant strains, accompanied by slow development of new antibiotics. In order to improve these treatments and engineer novel therapies, it is crucial that we increase our understanding of how these antibiotics interact with cellular metabolism. Evidence is increasingly building that the efficacy of antibiotics relies critically on downstream metabolic effects, in addition to inhibition of primary targets. Here we present a novel computational pipeline to expedite investigation of these effects: we combine computational modelling of metabolic networks with data from experimental screens on antibiotic susceptibility...

  3. Use Of synthetic solid scaffolds to mechanically support a chondrocyte-seeded peptide hydrogel for articular cartilage repair

    Ibañez, Jennifer R
    Post-traumatic osteoarthritis (PTOA) is a subtype of OA associated with cartilage defects caused by traumatic joint injury. Because articular cartilage has a limited innate healing response, due to its avascular, aneural, and alymphatic nature, these defects lead to chronic degenerative joint disease if left untreated. Current treatments to repair articular cartilage generally result in fibrocartilage that is mechanically and biochemically inferior to native hyaline tissue. This has motivated the development of tissue engineering strategies for cartilage defect repair. Hydrogel approaches have shown promising results in their ability to induce chondrogenesis, proliferation, and cartilage-like matrix production, but are often very soft...

  4. Streamlining and standardizing transcriptomic analysis in Amgen process development

    Weinberg, Kerry Rachel
    Building biological understanding of the Chinese Hamster Ovary (CHO) system used to manufacture therapeutic proteins is paramount to efficient CHO bioprocess optimization. This understanding can be built by analyzing and synthesizing biological data; such as transcriptomic (gene expression), proteomic (protein levels), or metabolomic (metabolite levels). This thesis describes a streamlined workflow for analyzing transcriptomic data. This streamlined workflow not only reduced the barrier to conducting the analysis but also reduced the analysis cycle time. With the use of this workflow, a number of historical Amgen microarray datasets were mined to identify gene expression signatures indicative of productivity. The result of...

  5. DNA polymerase beta inhibitor pamoic acid : toxicity to metakaryotic human cancer stem cells (HT-29)

    Kamath, Tushar Vinod
    Amitotic cells with large, hollow bell-shaped nuclei, or metakaryotic stem cells, are the post-embryonic stem cells of the fetal organs from about the fourth week post conception through physical maturity. These metakaryotic stem cells, after acquiring necessary genetic, and possibly other events, are also the stem cells of precancerous, cancerous and metastatic lesions of carcinogenesis. Furthermore, our lab has discovered that metakaryotic stem cells, both in fetal development and tumor growth, use a peculiar mode of DNA synthesis and segregation that involves inter alia expression of large amounts of RNA polymerase beta during DNA synthesis. It was hypothesized that an...

  6. A rapid, flexible and scalable DNA assembly platform for genome engineering and regulated gene expression applications in Plasmodium falciparum

    Nasamu, Armiyaw Sebastian
    Plasmodium falciparum is the deadliest malaria parasite. There is no approved vaccine to prevent this disease, and resistance to available antimalarial drugs is becoming widespread. Identification of parasite genes essential to survival and virulence could facilitate the development of novel therapeutics and vaccines. However, these efforts have been impeded by difficulties in manipulating the parasite's genome and functionally perturbing gene expression in a controlled way. Our lab has developed inducible systems to control P. falciparum gene expression, and has achieved successful editing of the P. falciparum genome using CRISPR/Cas9 technology. We have integrated these capabilities into a modular and scalable...

  7. Mitigating the effects of ribosome limitations on synthetic circuits via high-gain sRNA-mediated negative feedback

    Yazbek, John Elias
    Resource limitations in bacterial cells can present significant hurdles that preclude correct synthetic circuit behavior. In a simple circuit with one constitutively expressed protein and one protein whose expression is inducible, it has been shown that inducing the expression of the second protein causes a significant decrease in the level of the first. In this thesis, we explore the possibility of reducing the effects of resource limitations by adding a high-gain negative feedback loop to one of the circuits. The loop includes an sRNA construct. We explore different implementations of this circuit and model them mechanistically. Furthermore, we begin physically...

  8. Transcriptional divergence and conservation of human and mouse erythropoiesis

    Pishesha, Novalia
    Mouse models have been used extensively for decades and have been instrumental in improving our understanding of mammalian erythropoiesis. Nonetheless, there are several examples of variation between human and mouse erythropoiesis. We performed a comparative global gene expression study using data from morphologically identical stage-matched sorted populations of human and mouse erythroid precursors from early to late erythroblasts. Induction and repression of major transcriptional regulators of erythropoiesis, as well as major erythroid-important proteins, are largely conserved between the species. In contrast, at a global level we identified a significant extent of divergence between the species, both at comparable stages and...

  9. Distribution of mutant cells in human skin : exploration of the fetal-juvenile mutability hypothesis

    Kao, Leslie E
    The multiple "hits" carcinogenesis models are extensions of the cancer incidence theory developed by researchers from Nordling (1953), Armitage-Doll (1954 and 1957), Knudson (1971), Moolgavkar and Verzon (1979), to Moolgavkar and Knudson (1981), among others. These studies relate to the evolutionary process of normal tissue cells in an individual's organ from a normal stage to an initiated pre-neoplastic stage, and finally promoted to a neoplastic stage, resulting in tumorigenesis. The most significant impact of this type of research is to gain insight into the complex process of cancer development in humans. In the case of skin cancer, epidemiological and molecular...

  10. Crystal ball planning for analytics implementation in Singapore

    Fang, Cong, Ph.D. California State University, Los Angeles
    Amgen is building a new drug substance manufacturing site in Singapore (ASM). This project identified and mitigated the risks associated with implementing analytical technologies to facilitate the design and implementation of the quality control process in the new plant. Here, a systematic risk evaluation model was established to identify sources of high risks from implementing the analytical technologies in ASM, evaluated business cases and proposed technical strategies for risk mitigation. This project also included a case study about the cross-functional initiatives at Amgen, and made recommendations regarding how to bridge the gaps between the technology development in R&D and the...

  11. The role of polyphosphate kinase in long term survival of Helicobacter pylori

    Hansen, Jim (Jim Wade), 1970-
    by Jim Hansen.

  12. A comparative analysis of age-dependent and birth year cohort-specific cancer mortality data between Japan and the United States

    Márquez, Jose Angel, 1971-
    by Jose Angel Márquez, Jr.

  13. The spontaneous mutational spectrum of exon 2 and the high melting region of exon 3 of the human HPRT gene

    Glover, Curtis Lee X., 1971-
    by Curtis Lee X. Glover.

  14. The roles of diet and SirT3 levels in mediating signaling network changes in insulin resistance

    Lee, Nina Louise
    The goal of my research is to understand the mechanism by which high fat diets mediate insulin sensitivity and the role SirT3 plays in high fat diet-induced insulin resistance. Insulin resistance is defined as the inability of cells and tissues to respond properly to ordinary amounts of insulin and is a precursor to many metabolic diseases such as diabetes and cardiovascular disease. Obesity, brought on in large part by caloric excess from high fat diet feeding, is a major contributor to insulin resistance. The recent drastic increase in the prevalence of obesity makes it imperative that steps are taken to...

  15. Modulation of the response to cisplatin by nitric oxide and reactive oxygen species in melanoma cells

    Anderson, Chase Thaddeus Maceo
    Malignant melanoma causes the highest mortality rate in skin cancers. Although cisplatin has proved efficacious in the treatment of various solid tumors, melanoma seems particularly resistant to this chemotherapeutic drug. Reports show that melanoma patients whose tumors express nitric oxide (NO) synthase and/or nitrotyrosine are often faced with poor prognosis. Moreover, it has been shown that NO produced by melanoma cells sustains lower sensitivity to cisplatin toxicity in vitro. Because inflammatory products such as NO and reactive oxygen species (ROS) are associated with the genesis and evolution of cancer, we hypothesized that these oxidative species may regulate key components of...

  16. Electro-chemical stimulation of neuromuscular systems using ion-selective membranes : flexible device fabrication and motor unit recruitment order

    El Khaja, Ragheb Mohamad Fawaz
    Spinal Cord injury (SCI) leads to paralysis, decrease in quality of life and high lifetime medical costs. Direct nerve Functional Electrical Stimulation (FES) induces muscles to contract by electrically stimulating nerves, which shows promise for clinical applications in restoring muscle function in SC. However, Functional Electrical Stimulation is limited by the lack of graded response in muscle contraction and by high fatigability due to the reversal of recruitment order of motor units. Previous work showed that ion-selective membranes can be used to modulate Ca 2 ions in situ, decreasing the current threshold for nerve stimulation and eliciting a more graded...

  17. Behavioral and genetic characteristics of intestinal cell lineages in health and disease

    Kung, Kevin Su Yau
    The intestinal crypt is a highly dynamic system, as the entire epithelium is constantly turned over and renewed by the proliferative stem cells located at the bottom of the crypt. While this system is crucial for nutrient absorption, any derangements in the proliferative cells can quickly lead to cancer. In this thesis, we sought to better understand the behavioral and genetic characteristics of the different cell types along the intestinal crypt, in a mouse model. We first attempted to quantify the migration velocities and proliferative rates at a single-cell level using 5-ethynol-2'-deoxyuridine (EdU) pulse-chase labeling. While we observed marked differences...

  18. Developing osteoarthritis treatments through cartilage tissue engineering and molecular imaging

    Casasnovas Ortega, Nicole
    Tissue engineering can be applied to develop therapeutic techniques for osteoarthritis, a degenerative disease caused by the progressive deterioration of cartilage in joints. An inherent goal in developing cartilage-replacement treatments is ensuring that tissue-engineered constructs possess the same properties as native cartilage tissue. Biochemical assays and imaging techniques can be used to study some of the main components of cartilage and assess the value of potential therapies. Agarose and self-assembling peptides have been used to make hydrogels for in vitro culture of bovine bone marrow stromal cells (BMSCs) which can differentiate into chondrocytes, undergo chondrogenesis, and produce cartilage tissue. So...

  19. Cervical mucus prorperties stratifv risk for preterm birth

    Yao, Grace
    Preterm birth impacts 15 million babies every year, leading to morbidity, mortality, significant health care costs, and lifelong consequences. The causes of preterm birth are unknown, resulting in ineffective treatment, but it is correlated with ascension of vaginal bacteria through the cervix, which is normally protected by a dense mucus plug during pregnancy. This mucus plug, consisting of a tight meshwork of glycoproteins called mucins, should prevent pathogens from accessing the sterile uterine environment. Cervical mucus from women at high risk and low risk for preterm birth was collected and compared. The aim of this study was to discover differences...

  20. EMG control of prosthetic ankle plantar flexion

    Wang, Jing, M. Eng. Massachusetts Institute of Technology
    Similar to biological human ankle, today's commercially available powered ankle-foot prostheses can vary impedance and deliver net positive ankle work. These commercially available prostheses are intrinsically controlled. Users cannot intuitively change ankle controller's behavior to perform movements that are not part of the repetitive walking gait cycle. For example, when transition from level ground walking to descending stairs, user cannot intuitively initiate or control the amount of ankle angle deflexion for a more normative stair descent gait pattern. This paper presents a hybrid controller that adds myoelectric control functionality to an existing intrinsic controller. The system employs input from both...

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