An Electrically Active Microneedle Electroporation Array for Intracellular Delivery of Biomolecules

The objective of this research is the development of an electrically active microneedle array that can deliver biomolecules such as DNA and drugs to epidermal cells by means of electroporation. Properly metallized microneedles could serve as microelectrodes essential for electroporation. Furthermore, the close needle-to-needle spacing of microneedle electrodes provides the advantage of utilizing reduced voltage, which is essential for safety as well as portable applications, while maintaining the large electric fields required for electroporation. Therefore, microneedle arrays can potentially be used as part of a minimally invasive, highly-localized electroporation system for cells in the epidermis layer of the skin. This research consists of three parts: development of the 3-D microfabrication technology to create the microneedle array, fabrication and characterization of the microneedle array, and the electroporation studies performed with the microneedle array. A 3-D fabrication process was developed to produce a microneedle array using an inclined UV exposure technique combined with micromolding technology, potentially enabling low cost mass-manufacture. The developed technology is also capable of fabricating 3-D microstructures of various heights using a single mask. The fabricated microneedle array was then tested to demonstrate its feasibility for through-skin electrical and mechanical functionality using a skin insertion test. It was found that the microneedles were able to penetrate skin without breakage. To study the electrical properties of the array, a finite element simulation was performed to examine the electric field distribution. From these simulation results, a predictive model was constructed to estimate the effective volume for electroporation. Finally, studies to determine hemoglobin release from bovine red blood cells (RBC) and the delivery of molecules such as calcein and bovine serum albumin (BSA) into human prostate cancer cells were used to verify the electrical functionality of this device. This work established that this device can be used to lyse RBC and to deliver molecules, e.g. calcein, into cells, thus supporting our contention that this metallized microneedle array can be used to perform electroporation at reduced voltage. Further studies to show efficacy in skin should now be performed.Ph.D.Committee Chair: Mark G. Allen; Committee Member: Mark R. Prausnitz; Committee Member: Oliver Brand; Committee Member: Pamela Bhatti; Committee Member: Shyh-Chiang She

Herd Behaviors in Financial Markets

We investigate the herd behavior of returns for the yen-dollar exchange rate in the Japanese financial market. It is obtained that the probability distribution $P(R)$ of returns $R$ satisfies the power-law behavior $P(R) \simeq R^{-\beta}$ with the exponents $\beta=3.11$(the time interval $\tau=$ one minute) and 3.36($\tau=$ one day). The informational cascade regime appears in the herding parameter $H\ge 2.33$ at $\tau=$ one minute, while it occurs no herding at $\tau=$ one day. Especially, we find that the distribution of normalized returns shows a crossover to a Gaussian distribution at one time step $\Delta t=1$ day.Comment: 15 pages, 6 figure

Prvi nalaz oftalmostereze u teleta korejske domaće pasmine inficiranog virusom virusnog proljeva goveda.

A case of ophthalmosteresis associated with bovine viral diarrhea virus (BVDV) infection in a female Korea native calf is identified. This congenital anomaly is rare in cattle. Clinical examination revealed no further anomalies. The presence of BVDV antibodies was observed in serum. This is the first documented case of ophthalmosteresis in a calf specifically attributed to BVDV infection.Opisan je slučaj oftalmostereze (gubitka oka) u ženskog teleta korejske udomaćene pasmine povezane s virusom virusnog proljeva goveda. Ova kongenitalna anomalija rijetka je u goveda. Druge anomalije u istog teleta nisu bile uočene. U uzorku seruma teleta bila su dokazana specifična protutijela za virus virusnog proljeva goveda. Ovo je prvi slučaj oftalmostereze u teleta koji se pripisuje infekciji virusom virusnog proljeva