Non-Linear Optimization Applied to Angle-of-Arrival Satellite-Based Geolocation

Geolocation is a common application for satellite systems. This involves estimating an object\u27s location (herein called the subject) based on noisy satellite data. Many geolocation methods exist; however, none are tailored specifically for the unique problems faced by satellite systems. Some satellites are so far from the subject being localized that by the time the satellite receives a signal from the subject it might have moved appreciably. Furthermore, some satellites or terrestrial sensors may be much closer to the subject than others. Therefore, sensors may need to be weighted based upon their distance to the subject being localized. In addition, even if a subject can be localized, the confidence in this localization may be unknown. Non-linear optimization is proposed, implemented, and analyzed as a means of geolocating objects and providing confidence estimates from passive satellite line-of-sight data. Non-linear optimization requires an initial estimate. This estimate is provided by a triangulation method. The non-linear optimization then improves upon this estimate iteratively by finding estimates that are more likely to have produced the observed line-of-sight measurements. The covariance matrix of the geolocation parameters being estimated is naturally produced by the optimization which provides quantified confidence in the geolocation estimate. Simulations are developed to provide a means of evaluating the performance of the non-linear optimization algorithm. It was found that non-linear optimization can reduce the average error in geolocation estimates, provide improved estimation confidence, and accurately estimate its geolocation confidence for some subjects. The results from the theoretical development of the non-linear optimization algorithm and its simulated performance is quantified and discussed

The Related Transcriptional Enhancer Factor-1 Isoform, TEAD4216, Can Repress Vascular Endothelial Growth Factor Expression in Mammalian Cells

Increased cellular production of vascular endothelial growth factor (VEGF) is responsible for the development and progression of multiple cancers and other neovascular conditions, and therapies targeting post-translational VEGF products are used in the treatment of these diseases. Development of methods to control and modify the transcription of the VEGF gene is an alternative approach that may have therapeutic potential. We have previously shown that isoforms of the transcriptional enhancer factor 1-related (TEAD4) protein can enhance the production of VEGF. In this study we describe a new TEAD4 isoform, TEAD4216, which represses VEGF promoter activity. The TEAD4216 isoform inhibits human VEGF promoter activity and does not require the presence of the hypoxia responsive element (HRE), which is the sequence critical to hypoxia inducible factor (HIF)-mediated effects. The TEAD4216 protein is localized to the cytoplasm, whereas the enhancer isoforms are found within the nucleus. The TEAD4216 isoform can competitively repress the stimulatory activity of the TEAD4434 and TEAD4148 enhancers. Synthesis of the native VEGF165 protein and cellular proliferation is suppressed by the TEAD4216 isoform. Mutational analysis indicates that nuclear or cytoplasmic localization of any isoform determines whether it acts as an enhancer or repressor, respectively. The TEAD4216 isoform appears to inhibit VEGF production independently of the HRE required activity by HIF, suggesting that this alternatively spliced isoform of TEAD4 may provide a novel approach to treat VEGF-dependent diseases

Adipose Depletion and Apoptosis Induced by Trans-10, Cis-12 Conjugated Linoleic Acid in Mice

Objective: To compare the effectiveness of a conjugated linoleic acid (CLA) isomer mixture (mCLA) with each main isomer [trans-10,cis-12 CLA (CLA10,12) and cis-9,trans-11 CLA (CLA9,11)] in causing body lipid loss and adipose tissue apoptosis. Research Methods and Procedures: Mice selected over 16 generations for high (MH) or low (ML) energy expenditure and a control group (MC) were fed diets containing either soy oil or soy oil plus mCLA, CLA10,12, or CLA9,11 for 5 days in one study and 14 days in a second study. Results: Mice fed mCLA or CLA10,12 had less body lipid (p _ 0.05), smaller retroperitoneal fat pads (p \u3c 0.05), and ate less (p \u3c 0.01) than mice fed no CLA or CLA9,11 for 5 days. Mice consuming 1% mCLA or 0.5% CLA10,12 gained less weight (p \u3c 0.01) and had less body lipid (p \u3c 0.05) and smaller epididymal (p \u3c 0.05) and retroperitoneal fat pads (p \u3c 0.01) than mice consuming either control or 0.5% CLA9,11-containing diets for 14 days. Only mCLA and CLA10,12 increased apoptosis in retroperitoneal fat pads (p \u3c 0.01). The effects of mCLA and CLA10,12 were independent of genetic line except for the effect on adipocyte apoptosis. Mice of the MH line were slightly less sensitive than MC or ML mice to CLA-induced adipose tissue apoptosis. Discussion: CLA10,12, but not CLA9,11, can induce both body fat loss and adipose apoptosis. Although mice of a genotype with less body fat and greater metabolic rate and feed intake appear less sensitive, these CLA effects are robust for mice of varying metabolic background