Pre-shuttle lidar system research

Included are the results of the initial phase of a simulation study in connection with photomultiplier tubes (PMT) and associated networks and an analytical study of atmospheric physics (including multiscattering) leading to modeling studies in connection with differential absorption lidar (DIAL) observations. This effort was in support of the ER-2 aircraft DIAL projects

Optimization of the Formulation and Design of Oligonucleotide-based Pharmaceuticals for the Purpose of Gene Therapy

Oligonucleotides (ONs) are short sequences of nucleic acids which may be used in a therapeutic context to modulate gene expression. According to their target, ONs can be classified into two main classes: antisense ONs which target mRNA and antigene ONs that target chromosomal DNA. In order to be pharmaceutically efficient, both kinds of ONs have to possess enough stability against degrading enzymes and rapid clearance. They must pass the cell membrane, and in some cases the nuclear membrane, and bind with enough specificity and high affinity to their target site to successfully exert their desired effect. In fact, the use of natural nucleic acids as drugs is hindered by both their inherent instability in biological fluids and their highly charged nature, which hampers their cellular uptake. Therefore, research in the field of ON-based pharmaceuticals focuses on two main strategies: chemical modification of nucleic acids to produce analogues with better stability and binding properties, and development of delivery systems to further stabilize the ONs and enhance their cellular uptake. Splice-switching antisense ONs (SSOs) made of phosphorothioate 2’-O-methyl RNA are promising therapeutics for several disorders caused by aberrant splicing. However, as other ONs, their usefulness is hindered by the lack of efficient delivery. In the first study of this thesis, four amino acid modified versions of the well-known polycation polyethylenimine (PEI) were evaluated for the formulation and delivery of SSOs. The formulations were physically characterized via assessment of their particle size and stability and this characterization was then correlated to their splice-correction efficiency after transfection into mammalian cells. Tyrosine-modified PEI (PEIY) was identified as a successful delivery system for SSOs as shown by splice-correction efficiency of 80% measured in HeLa705; a cell-model containing a mutated –globin intron sequence found in –thalassemia splicing disorder. In the second study, a new cell penetrating peptide (PepFect 14) was developed and investigated for the formulation and delivery of SSOs using cell-models for two splicing disorders; -thalassemia and Duchenne muscular dystrophy. The feasibility of incorporating this delivery system into solid formulations via solid dispersion technique was also demonstrated. The formed solid formulations were as active as the freshly prepared nanocomplexes in solution even when stored at elevated temperatures for several weeks. In the third study, PepFect 14 was evaluated for the formulation and delivery of another kind of ONs: short interfering RNA (siRNA) in different cell lines. RNA interference effect was obtained at low siRNA doses with a unique kinetic profile. Solid formulations were then prepared and assessed for their stability in gastric conditions. PF14/siRNA solid formulations showed marked stability after incubation with simulated gastric fluid, which is extremely acidic and contains proteolytic enzymes. The fourth study of this thesis addressed design optimization of the newly developed antigene ON, Zorro-LNA (Zorro). Here, double-strand invasion was proven as the mechanism by which Zorro binds to duplex DNA. The original Zorro, targeting both strands of the DNA duplex, was made of two ONs connected via a 7-nucleotide linker. In this report, the possibility to synthesize Zorro as a bi-directional single-stranded ON was investigated, thus reducing the size, facilitating the design and improving Zorro efficiency. In conclusion, this thesis has dealt with developing formulation strategies for two different types of ON-based pharmaceuticals; SSOs and siRNA. Optimizing the design of Zorro LNA as an antigene ON has been also investigated. These findings may represent a step in the development of ON-based drug products as a new class of therapeutics

Brewster and pseudo-Brewster angles of uniaxial crystal surfaces and their use for determination of optical properties

Brewster and pseudo-Brewster angles are defined for surfaces of transparent and absorbing uniaxial crystals parallel and perpendicular to the optic axis. Two Brewster angles of a transparent uniaxial crystal surface parallel to the optic axis, measured when the optic axis is oriented perpendicular and parallel to the plane of incidence, readily determine the ordinary and extraordinary indices No and Ne. No and Ne can also be obtained from two Brewster angles measured on a surface perpendicular to the optic axis in contact with two media of different refractive indices. Conditions for the existence of two Brewster angles are discussed. The complex No and Ne of an absorbing uniaxial crystal can be derived from pseudo-Brewster-angle and minimum-reflectance data obtained in two symmetrical orientations of a surface parallel to the optic axis. An approximate, but accurate, explicit inversion procedure is presented for this purpose

Inversion of the nonlinear equations of reflection ellipsometry for uniaxial crystals in symmetrical orientations

The complex ordinary (No) and extraordinary (Ne) refractive indices of an absorbing uniaxial crystal can be determined using reflection ellipsometry. The measurements are taken with the optic axis parallel and perpendicular to the crystal’s surface. The equations obtained are solved without resort to iterative methods; No and Ne are determined separately. Sixteen solution sets (No, Ne) are obtained and the correct solution can be easily identified. We present an optimum angle of incidence that minimizes the relative errors in No and Ne

Single-element rotating-polarizer ellipsometer for film-substrate systems

A novel and very simple ellipsometer for the characterization of film-substrate systems that employs one rotating optical element (a polarizer) is proposed. The ellipsometer is based on detecting the angles of incidence at which a film-substrate system has equal amplitude attenuations for light polarized parallel (p) and perpendicular (s) to the plane of incidence. At a certain wavelength, the film thickness of the filmsubstrate system has to lie within permissible-thickness bands (PTB) for the technique to apply

Constant-psi constant-delta contour maps: applications to ellipsometry and to reflection-type optical devices

Constant-psi constant-delta contour maps in the reduced angle-of-incidence-film-thickness plane that are useful in ellipsometry and in design of reflection-type optical devices are discussed. As a specific example, a contour map is given for the SiO2-Si film-substrate system at the 6328-Å He-Ne laser wavelength

Constant-psi constant-delta contour maps: applications to ellipsometry and to reflection-type optical devices

Constant-psi constant-delta contour maps in the reduced angle-of-incidence-film-thickness plane that are useful in ellipsometry and in design of reflection-type optical devices are discussed. As a specific example, a contour map is given for the SiO2-Si film-substrate system at the 6328-Å He-Ne laser wavelength

Principal angle, principal azimuth, and principal-angle ellipsometry of film-substrate systems

When the film thickness is considered as a parameter, a system composed of a transparent film on an absorbing substrate (in a transparent ambient) is characterized by a range of principal angle ø¯min ≤ ø¯ ≤ ø¯max over which the associated principal azimuth ψ¯ varies between 0° and 90° (i.e., 0° ≤ ψ¯ ≤ 90°) and the reflection phase difference Δ assumes either one of the two values: +π/2 or −π/2. We determine the principal angle ø¯(d) and principal azimuth ψ¯(d) as functions of film thickness d for the vacuum-SiO2-Si system at several wavelengths as a concrete example. When the film thickness exceeds a certain minimum value, more than one principal angle becomes possible, as can be predicted by a simple graphical construction. We apply the results to principal-angle ellipsometry. (PAE) of film-substrate systems; the relationship between ø¯ and ψ¯ during film growth is particularly interesting