Abstract: It has been discovered that lipophilic hormones that interact with cytosolic or nuclear receptors regulate APP expression and synthesis, through modification of APP mRNA stability and/or regulation of APP gene transcription and translation activities. These studies demonstrate that the treatment of brain cells with estrone or 17&bgr;-estradiol results in a reduction in the level of APP holoprotein expression, without a concomitant change in the total level of cell protein. The reduction in the level of APP holoprotein caused by estrone or 17&bgr;-estradiol is also expected to reduce the production of neurotoxic APP fragments. In as much as estrogen deficiency in postmenopausal women is associated with a higher incidence of Alzheimer's disease, this discovery opens the possibility that estrogen therapy may prevent some of the neurodegenerative and cognitive changes associated with Alzheimer's disease, aging and other disease conditions associated with such neurodegenerative and cognitive decline.

Abstract: The compositions and methods disclosed herein provide heterobifunctional programmable genotoxic compounds that can be designed to kill selected cells present in a heterogenous cell population. The present compounds comprise a first agent that inflicts damage on cellular DNA, and a second agent that attracts a macromolecular cell component such as a protein, which in turn shields genomic lesions from repair. Unrepaired lesions therefore persist in the cellular genome and contribute to the death of selected cells. In contrast, lesions formed in nonselected cells, which lack the cell component, are unshielded and thus are repaired. As a result, compounds described herein are less toxic to nonselected cells. Compounds of this invention can be designed to cause the selective killing of transformed cells, viral-infected cells and the like.

Abstract: A process for placing a part in a predetermined region is described. The part is defined by a part boundary and the predetermined region is defined by a region boundary. The process includes the steps of identifying corner locations of the bounded region in which parts may be placed and minimizing waste during part placement. Waste minimization may be accomplished by placing the part in a plurality of different locations in the predetermined region and at each location identifying area elements which extend from the part boundary of the part, computing the area of each of the area elements, assigning a weight value to each of the area elements and computing a weighted sum of the area elements surrounding the part boundary in each of the locations of the predetermined region. Waste is minimized at a first one of the plurality of locations of the predetermined boundary having the lowest weighted sum.

Abstract: Samples such as thin polymeric films are analyzed using optically induced phonons by excitation of the sample using radiation preferably absorbed by the sample and probe radiation, preferably not absorbed by the sample, that is diffracted from the surface of the sample. The pulse width of the probe is preferably on the order of the detectable diffraction signal so that the phonon decay from each excitation pulse can be detected and analyzed. The technique is applicable to various samples by inducing a ripple morphology on the sample surface and detection of light diffracted substantially from surface ripple.

Abstract: Injectable nanoparticles or microparticles are provided that are not rapidly cleared from the blood stream by the macrophages of the reticuloendothelial system, and that can be modified as necessary to achieve variable release rates or to target specific cells or organs as desired. The terminal hydroxyl group of the poly(alkylene glycol) can be used to covalently attach onto the surface of the injectable particles biologically active molecules, including antibodies targeted to specific cells or organs, or molecules affecting the charge, lipophilicity or hydrophilicity of the particle. The surface of the particle can also be modified by attaching biodegradable polymers of the same structure as those forming the core of the injectable particles. The injectable particles include magnetic particles or radioopaque materials for diagnostic imaging.

Abstract: A method is disclosed for treating tissue in response to a stimulus generated by the tissue. In one embodiment, the method transdermally treats an organism in response to a stimulus. In this embodiment, the medication is applied to epidermis of the organism, and the epidermis is electroporated in response to a stimulus, whereby the medication passes through the epidermis at a rate sufficient to alter the stimulus, thereby transdermally treating the organism. In another embodiment, the method measures a blood component content of blood. A portion of epidermis is electroporated to cause an aqueous fluid to be directed through an electroporated epidermis to a surface of the epidermis. Thereafter, the blood component content of the aqueous fluid is measured for correlation with a known aqueous fluid blood component content associated with a known concentration of blood component in the blood. The blood component concentration of the blood can thereby be measured.

Abstract: Composites of materials in which the matrix material does not spontaneously or readily wet the disperse phase and in which the volume fraction of the disperse phase is less than that formed in a packed bed of dispersate particles can be made effectively by an indirect method of infiltrating a packed bed of dispersate particles, using pressure or other mechanical force as needed to overcome poor wetting and form an intermediate concentrated composite. The concentrated composite is then mixed with additional matrix-forming material to produce the finally desired composite. The technique is particularly valuable for composites with ceramic dispersates and metal or alloy matrixes.

Abstract: Compositions useful in the treatment of disturbances of appetite, disturbances of mood, or both, nicotine withdrawl associated as well as experienced by individuals after discontinuing tobacco use as methods of use therefor. The compositions include serotoninergic drugs, such as d-fenfluramine and fluoxetine.

Abstract: A Q-switched laser having a gain medium disposed within a first cavity and a second cavity whose optical path length is adjustable such that the quality of the first resonant cavity is affected. One aspect of the invention is the changing of the physical path length of the second cavity so as to affect the reflectivity of a mirror common to both cavities as seen from the first cavity. Another aspect of the invention is the incorporation, within the second cavity, of a material whose refractive index or absorption coefficient can be varied by the application of an electric field, a magnetic field, a temperature change or an applied pressure.

Abstract: The conjugate addition of Grignard reagents to alpha, beta-unsaturated carbonyl compounds using a series of novel catalysts is described. The catalysts comprise copper(I) complexes with ligand systems comprising either tropocoronand macrocycles or N,N'-dialkylsubstituted aminotroponeimines.