Protein disulfide isomerase (PDI) is an endoplasmic reticulum (ER)-resident chaperone with oxidoreductase and isomerase activity. Unique to its normal function, PDI also appears to disassemble the A1 subunits of cholera toxin (CT) and heat-labile enterotoxin (LT). It does so using an unfolding mechanism that knocks the catalytic A1 subunit away from the rest of the holotoxin. Release of the A1 subunit is linked to the diarrheal diseases caused by V. cholerae and enterotoxicogenic E. coli (ETEC). Due to the previously established difference in disease potency between CT and LT, we investigated and established a distinction between the two toxins in their efficacy of disassembly by PDI. We further identified four amino acid differences between the CTA2 and LTA2 linkers, which connect the A1 and cell-binding B subunits of both toxins, as the basis for this difference. We believe these four amino acids result in changes to holotoxin architecture that lead to antiparallel binding of PDI to LT as opposed to CT, which translates to a loss of momentum for the physical disassembly of LT. We have shown this through algorithmic simulations of the binding event between PDI and either CT or LT. We hypothesized the unfolding mechanism of PDI, which dislodges the A1 subunit of both CT and LT, can also break down neurotoxic aggregates of β-Amyloid (AB) and α-Synuclein (AS). PDI is known to inhibit the aggregation of the amyloid proteins. We demonstrated here that PDI could also reverse oligomeric and post-oligomeric aggregates of AB and AS, respectively. Our work sheds light on the specifics of PDI's novel physical mechanism as well as introduce it as a possible therapeutic for both Alzheimer's and Parkinson's disease due to its unique ability to disaggregate early fibrillar structures of AS and AB proteins.

The effects of taste masking are determined by interactions between drug and excipients as well as the microstructures of the particulate drug delivery systems (DDS). Cyclodextrin (CD) is a widely used taste masking agent, to which the relationship between kinetic parameters (Ka and Kd) of a drug and taste masking remains unexplored, which is investigated for the first time in this study. A data base of the kinetic parameters for drug-CD was established by Surface Plasmon Resonance Imaging (SPRi) and High Performance Affinity Chromatography (HPAC). Combined with the electronic tongue, Ka and Kd based models for the taste masking effect of HP-β-CD were successfully established and applied to the prediction of taste masking effects. Paracetamol was used as a model drug for taste masking formulation optimization. As well as drug release the microstructure of solid DDS has considerable influence on drug taste. The microstructure of lipid microspheres and the molecular distribution of drug and excipients in lipid microspheres were investigated by Synchrotron radiation-based micro-computed tomography (SR-μCT) and Synchrotron radiation-based Fourier-transform infrared spectromicroscopy (SR-FTIR), respectively. The results demonstrated that the polymeric formulation components as well as shape and particle size of the drug were the key factors to taste masking of paracetamol by inhibiting bust release thereby reducing the interaction intensity of the bitterness. The FTIR absorption spectra confirmed the deposition and formation of chitosan and gelatin films on the drug microsphere surface by layer-by-layer coating. In conclusion, this research demonstrates the molecular kinetic basis of CD taste-masking as well as microstructural basis of particle systems for bitter taste masking.

Optical fibers are getting significant considerations in the field of the sensors and sensing beyond its applications in optical communications. Because of several advantages, e.g., low profile of the sensors, immunity to electromagnetic noises, the ability of multiplexing, etc., the use of the fiber optic sensor is increasing in the field of physical, chemical, and biomedical sensing. In this study, we have developed two new fiber optic sensors based on fiber loop ringdown technique (FLRD) and have demonstrated their applications in the field of sensing. In the first part of this study, we report on the development of a high-sensitivity FLRD strain sensor. For the design of the strain sensor, the fiber loop was cut at the middle, and then the two fiber ends from broken fiber loop were cleaved and aligned carefully to couple the light from one end to another end. Any strain during the measurement changes the alignment of the fiber ends, consequently, the ringdown time changes. With this scheme, the FLRD strain sensor has shown the strain detection limit of 65 nanostrain, which is five times better than any FLRD strain sensors reported in the literature. Furthermore, The FLRD strain sensors were successfully embedded into prestressed concrete-beams.The FLRD strain sensor was able to monitor stress on a post-tensioned rod, as well as the load applied on the concrete-beam during the three-point loading test, thus exhibiting immense potential in structural health monitoring. For the chemical sensor, a new scheme of interrogation for a fiber optic surface plasmon sensor was developed with the use of the FLRD technique. A gold nanolayer was deposited on an uncladded fiber section, and the fiber section was integrated into the FLRD system as a sensor head. The gold layer facilitates for increased interaction of sample of interest, with the light pulse confined in the fiber waveguide. Moreover, with the affinity of the gold with specific biomolecules, the sensor has the potential for applications in biochemical sensing. In the experiment, the SP-FLRD sensor was used for refractive index sensing, and index detection limit of 4.6×10-5 RIU was achieved.

Film thickness, free carrier concentration and free carrier mobility are critical figures of merit for silicon carbide epitaxial growth. Room temperature Fourier Transform Infrared (FTIR) reflection spectroscopy can estimate these parameters non-destructively and is capable of high-resolution wafer mapping. Commercially available equipment has greatly simplified the application of this technique by coupling a high performance automated spectrometer with model-based data analysis and interpretation based on the personal computer. While powerful numerical techniques run fast and efficient on modern computers, it is essential that low-order, well-conditioned models are needed. The observed reflectance spectrum is the result of reflection and refraction of light at different interfaces due to constructive and destructive interference. The estimation of film thickness and free carrier concentration for single epitaxial layers has been improved by studying the Longitudinal Optical Phonon Plasmon (LPP) coupled modes. However, the addition of multiple layers introduces many degrees of freedom, which complicates parameter extraction. The multiple epitaxial layer stacks studied were intended for Metal Semiconductor Field Effect Transistor (MESFET?s) on both conducting and semi-insulating substrates. The thickness estimation of the n-channel in the MESFET stack on semi-insulating substrate is improved by preconditioning the curve fit for plasma frequency obtained from doping estimation from capacitance voltage profiling or by observing an LPP- peak.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.