Cardiovascular Tissue Engineered Constructs for Patients With Diabetes

Clinical translation of cardiovascular tissue engineering (CVTE) is rapidly shifting from concept to application, granting a myriad of opportunities for the treatment of cardiovascular disorder (CVD). There remains, however, a critical hurdle to overcome: the application of tissue engineering to a comprised patient - more specifically, a patient with diabetes mellitus (DM). The alarming prevalence of DM is of great concern due to its duel threat as both a risk factor for CVD and a predictor of biomedical device failure. Elevated levels of inflammation and impaired wound healing are hallmarks of DM contributing to cardiomyopathy, atherosclerosis, and valve disease. The primary focus of my research was two-fold: 1) to evaluate diabetes-related complications to scaffolds and stem cells used for cardiovascular tissue engineering; and 2) to attenuate these complications by addition of a non-toxic matrix-binding polyphenolic antioxidant, pentagalloyl glucose (PGG). Two types of extracellular matrix (ECM) scaffolds were investigated in this study: collagen-based and elastin based. In vivo biocompatibility studies revealed that the diabetic environment invoked detrimental alterations to the matrix scaffolds including crosslinking, advanced glycation end product (AGE) accumulation, and elevated inflammation. However, these complications could be mitigated by scaffold pre- treatment with PGG. By virtue of its antioxidant properties, PGG halted diabetes-related stiffening, AGE accumulation, inflammation, and calcification. The effect of seeded autologous adipose stem cells (ASCs) were also investigated in vivo. We observed immunomodulatory capabilities of ASCs to the implanted constructs by reducing the pro-inflammatory response, shifting the polarization of macrophages towards constructive remodeling, and preventing inflammation-driven calcification. The combination of ASCs with PGG formed a truly diabetic-resistant construct capable of combating glycoxidation, crosslinking, destructive inflammation, and calcification. The overall goal of this research was to establish the framework of clinical translation of tissue engineering. Tissue engineering is often heralded as a patient- tailored approach for disease treatment; however, our translational efforts are useless if we cannot address the comorbidities associated with the patient. This research takes a step towards the development of a deliverable and robust tissue engineered construct for use in treatment of cardiovascular disease

Excitation and Imaging of Resonant Optical Modes of Au Triangular Nano-Antennas Using Cathodoluminescence Spectroscopy

Cathodoluminescence (CL) imaging spectroscopy is an important technique to understand resonant behavior of optical nanoantennas. We report high-resolution CL spectroscopy of triangular gold nanoantennas designed with near-vacuum effective index and very small metal-substrate interface. This design helped in addressing issues related to background luminescence and shifting of dipole modes beyond visible spectrum. Spatial and spectral investigations of various plasmonic modes are reported. Out-of-plane dipole modes excited with vertically illuminated electron beam showed high-contrast tip illumination in panchromatic imaging. By tilting the nanostructures during fabrication, in-plane dipole modes of antennas were excited. Finite-difference time-domain simulations for electron and optical excitations of different modes showed excellent agreement with experimental results. Our approach of efficiently exciting antenna modes by using low index substrates is confirmed both with experiments and numerical simulations. This should provide further insights into better understanding of optical antennas for various applications.Comment: To be published in JVST B (accepted, Sep 2010) (15 pages, 6 figures, originally presented at EIPBN 2010

Flash memory management system and method utilizing multiple block list windows

The present invention provides a flash memory management system and method with increased performance. The flash memory management system provides the ability to efficiently manage and allocate flash memory use in a way that improves reliability and longevity, while maintaining good performance levels. The flash memory management system includes a free block mechanism, a disk maintenance mechanism, and a bad block detection mechanism. The free block mechanism provides efficient sorting of free blocks to facilitate selecting low use blocks for writing. The disk maintenance mechanism provides for the ability to efficiently clean flash memory blocks during processor idle times. The bad block detection mechanism provides the ability to better detect when a block of flash memory is likely to go bad. The flash status mechanism stores information in fast access memory that describes the content and status of the data in the flash disk. The new bank detection mechanism provides the ability to automatically detect when new banks of flash memory are added to the system. Together, these mechanisms provide a flash memory management system that can improve the operational efficiency of systems that utilize flash memory

Treatment to Render Implants Resistant to Diabetes

Disclosed is a medical device treated with a phenolic compound and a process for treating a device with the phenolic compound. For example, a collagen or elastin-based scaffold can be treated with pentagalloyl glucose (PGG). The treated scaffold can become resistant to glycoxidative stress associated with advanced glycation end products (AGEs) that are present in a hyperglycemic environments associated with diabetes mellitus. The treated scaffold can exhibit a reduced increase in stiffness as compared to an untreated scaffold. The treated scaffold can also exhibit reduced inflammation without negatively affecting the ability of the scaffold to remodel in vivo

Injecting Errors for Testing Built-In Test Software

Two algorithms have been conceived to enable automated, thorough testing of Built-in test (BIT) software. The first algorithm applies to BIT routines that define pass/fail criteria based on values of data read from such hardware devices as memories, input ports, or registers. This algorithm simulates effects of errors in a device under test by (1) intercepting data from the device and (2) performing AND operations between the data and the data mask specific to the device. This operation yields values not expected by the BIT routine. This algorithm entails very small, permanent instrumentation of the software under test (SUT) for performing the AND operations. The second algorithm applies to BIT programs that provide services to users application programs via commands or callable interfaces and requires a capability for test-driver software to read and write the memory used in execution of the SUT. This algorithm identifies all SUT code execution addresses where errors are to be injected, then temporarily replaces the code at those addresses with small test code sequences to inject latent severe errors, then determines whether, as desired, the SUT detects the errors and recover

Cytokines and Growth Factors Stimulate Hyaluronan Production: Role of Hyaluronan in Epithelial to Mesenchymal-Like Transition in Non-Small Cell Lung Cancer

In this study, we investigated the role of hyaluronan (HA) in non-small cell lung cancer (NSCLC) since close association between HA level and malignancy has been reported. HA is an abundant extracellular matrix component and its synthesis is regulated by growth factors and cytokines that include epidermal growth factor (EGF) and interleukin-1β (IL-1β). We showed that treatment with recombinant EGF and IL-1β, alone or in combination with TGF-β, was able to stimulate HA production in lung adenocarcinoma cell line A549. TGF-β/IL-1β treatment induced epithelial to mesenchymal-like phenotype transition (EMT), changing cell morphology and expression of vimentin and E-cadherin. We also overexpressed hyaluronan synthase-3 (HAS3) in epithelial lung adenocarcinoma cell line H358, resulting in induced HA expression, EMT phenotype, enhanced MMP9 and MMP2 activities and increased invasion. Furthermore, adding exogenous HA to A549 cells and inducing HA H358 cells resulted in increased resistance to epidermal growth factor receptor (EGFR) inhibitor, Iressa. Together, these results suggest that elevated HA production is able to induce EMT and increase resistance to Iressa in NSCLC. Therefore, regulation of HA level in NSCLC may be a new target for therapeutic intervention