LAYERED, FLEXIBLE DRUG DELIVERY FILMS FOR THE PREVENTION OF FIBROTIC SCAR TISSUE FORMATION

Open wounds account for about 50% of military injuries and 10% of non‐fatal traffic injuries. Scar tissue formation in these wounds may be reduced or prevented if treated with a combination of molecules whose release is tuned to the healing phases. The goal of this research was to develop flexible, layered drug delivery films for sequential, localized release of anti‐inflammatory, anti‐oxidant, and anti‐fibrotic molecules to soft tissue. Films were composed of cellulose acetate phthalate (CAP) and Pluronic F‐127 (Pluronic). To impart flexibility, plasticizers, triethyl citrate (TEC) or tributyl citrate (TBC), were added. Mechanical analysis was performed on films as prepared and following phosphate‐buffered saline incubation to determine property changes after implantation. Tensile tests revealed higher plasticizer content increased film elongation but decreased elastic modulus and ultimate tensile strength. TEC films elongated twice as much as those with TBC. After incubation, properties increased because plasticizer leached from films. Micro computerized tomography and scanning electron microscopy determined how erosion and plasticizer leaching affected the film’s structures before and after incubation. Porosity increased as plasticizer content increased; however, plasticizer content did not significantly affect erosion rates. Next, effects of drugs with plasticizers on film erosion, release, and mechanical properties were investigated. Films were loaded with quercetin, an anti‐oxidant, or pirfenidone, an anti‐fibrotic, and plasticized with TEC or TBC. TEC‐plasticized films containing quercetin released drug at a slower rate than TBC films. Pirfenidone‐loaded films released drug at a faster rate than erosion occurred for both plasticizers. Increased pirfenidone loading resulted in significantly higher modulus and decreased elongation, an anti‐plasticizer effect. Increasing quercetin loading significantly increased elongation. Size, solubility, and structure differences between quercetin and pirfenidone affected drug interaction with the films and the consequent mechanical and release properties. Cell studies found TBC to be toxic even in low concentrations. Consequently, only TEC was further analyzed. Layered devices containing two drugs demonstrated sequential release regardless of drug order. Plasticizer concentration did not significantly affect the release profiles. Lastly, in vitro and in vivo 9‐layered device studies sequentially released drugs confirming the research objective: sequential, local release of anti‐inflammatory, anti‐oxidant, and anti‐fibrotic molecules from CAPPluronic films

Oxidatively damaged proteins of heart mitochondrial electron transport complexes

AbstractProtein modifications, such as carbonylation, nitration and formation of lipid peroxidation adducts, e.g. 4-hydroxynonenal (HNE), are products of oxidative damage attributed to reactive oxygen species (ROS). The mitochondrial respiratory chain Complexes I and III have been shown to be a major source of ROS in vitro. Additionally, modifications of the respiratory chain Complexes (I–V) by nitration, carbonylation and HNE adduct decrease their enzymatic activity in vitro. However, modification of these respiratory chain complex proteins due to in vivo basal level ROS generation has not been investigated. In this study, we show a basal level of oxidative damage to specific proteins of adult bovine heart submitochondrial particle (SMP) complexes, and find that most of these proteins are localized in the mitochondrial matrix. We postulate that electron leakage from respiratory chain complexes and subsequent ROS formation may cause damage to specific complex subunits and contribute to long-term accumulation of mitochondrial dysfunction

Einfluss der herdenleistungsniveau auf nachkommenbullenprüfung

International audienc

WinNTGen : Creation of a Windows NT 5.0+ network traffic generator

Thesis (M.Eng.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2003.Includes bibliographical references (leaves 65-67).The Lincoln Adaptable Real Time Information Assurance Testbed (LARIAT) project is the first fully automatable network testbed for the evaluation of information assurance (IA) technologies. It allows researchers to easily set up experiments that evaluate the accuracy of host-based and network-based intrusion detection systems (IDSs). Initially, the network traffic it could produce used UNIX services and protocols as implemented for the Linux and Solaris platforms. However, due to the widespread deployment of Windows-based systems in production environments, it is necessary to include Windows-based traffic when testing IA systems in order to provide a comprehensive evaluation. This thesis describes WinNTGen, a Windows network traffic generation system that integrates into the existing LARIAT framework and enables it to produce Windows-based network traffic. To do this, WinNTGen simulates the actions of a user controlling applications that in turn use network resources. This frees WinNTGen from the need to re-implement network protocols and allows it to operate at a higher level of abstraction. WinNTGen controls applications via loadable libraries that encapsulate the manner in which a typical user interacts with a particular application. The statistical parameters that specify the behavior of a user with each application are derived from real users' behavioral data as they interacted with each application. The system is flexible and extensible so that different versions of the same application as well as additional applications can be controlled by modifying and adding libraries. Finally, the reality and the throughput of the network traffic produced by the WinNTGen system are evaluated.by Jesse C. Boothe-Rabek.M.Eng

Laser-induced Reactions in a Deep UV Resist System: Studied with Picosecond Infrared Spectroscopy

One of the most technologically important uses of organic photochemistry is in the imaging industry where radiation-sensitive organic monomers and polymers are used in photoresists. A widely-used class of compounds for imaging applications are diazoketones; these compounds undergo a photoinduced Wolff rearrangement to form a ketene intermediate which subsequently hydrolyses to a base-soluble, carboxylic acid. Another use of organic molecules in polymer matrices is for dopant induced ablation of polymers. As part of a program to develop diagnostics for laser driven reactions in polymer matrices, we have investigated the photoinduced decomposition of 5-diazo-2,2-dimethyl-1,3-dioxane-4,6-dione (5-diazo Meldrum`s acid, DM) in a PMMA matrix using picosecond infrared spectroscopy. In particular, irradiation of DM with a 60 ps 266 nm laser pulse results in immediate bleaching of the diazo infrared band ({nu} = 2172 cm{sup -1}). Similarly, a new band appears within our instrument response at 2161 cm{sup -1} (FWHM = 29 cm{sup -1}) and is stable to greater than 6 ns.; we assign this band to the ketene photoproduct of the Wolff rearrangement. Using deconvolution techniques we estimate a limit for its rate of formation of {tau} < 20 ps. The linear dependence of the absorbance change with the pump power (266 nm) even above the threshold of ablation suggest that material ejection take place after 6ns

Ultraviolet curing of acrylic systems: Real-time Fourier transform infrared, mechanical, and fluorescence studies

The photopolymerization of acrylic-based adhesives has been studied by Fourier transform infrared and fluorescence analysis in real time. Real-time infrared spectroscopy reveals the influence of the nature of the photoinitiator on the kinetics of the reaction. Furthermore, the incident light intensity dependence of the polymerization rate shows that primary radical termination is the predominant mechanism during the initial stages of the curing of the acrylic system with bis(2,4,6-trimethylbenzoyl) phenyl phosphine oxide (TMBAPO) as a photoinitiator. The fluorescence intensity of selected probes increases during the ultraviolet curing of the adhesive, sensing microenvironmental viscosity changes. Depending on the nature of the photoinitiator, different fluorescence&-conversion curves are observed. For TMBAPO, the fluorescence increases more slowly during the initial stage because of the delay in the gel effect induced by primary radical termination. Mechanical tests have been carried out to determine the shear modulus over the course of the acrylic adhesive ultraviolet curing. In an attempt to extend the applications of the fluorescence probe method, we have undertaken comparisons between the fluorescence changes and shear modulus. Similar features in both curves confirm the feasibility of the fluorescence method for providing information about microstructural changes during network formation.The authors thank the Union European Commission for funding through the BRITE-Euram Project (BE97-4472). Gratitude is also extended to Plan Nacional I+D+I (Ministerio de Ciencia y Tecnología) for its financial support (MAT2000-1671) and to Comunidad Autónoma de Madrid (07N/0002/1998). The authors thank K. Dietliker (Ciba Specialty Chemicals) for providing the photoinitiators and Loctite España for providing the adhesives