CONTRASTING EFFECTS OF AN MDM2 FUNCTIONAL POLYMORPHISM ON TUMOR PHENOTYPES

Cancer predisposition by the cooperation of genetic variants, such as single nucleotide polymorphisms (SNPs), may be of much greater significance to public health than previously appreciated. Functional polymorphisms are genetic variants that alter gene function. Meta-analyses associate many functional polymorphisms with cancer risk. The MDM2 SNP309G allele is a cancer-associated functional polymorphism positioned in the MDM2 P2 promoter that enhances transcription factor SP1 binding, resulting in elevated levels of MDM2 concomitant with decreased p53 tumor-suppressor activity. Mdm2SNP309G/G mice are more prone to spontaneous tumor formation than Mdm2SNP309T/T mice, providing direct evidence for the impact of this SNP on tumor development. We examined the impact of SNP309 on cancer risk in response to environmental factors by treating SNP309 mice with ionizing radiation, UVB, or Benzo(a)pyrene. The results show that SNP309G cooperates with ionizing radiation to exacerbate tumor development. Contrastingly, ultraviolet B light or Benzo(a)pyrene exposure of skin indicates that SNP309G allele protects against squamous cell carcinoma susceptibility. These contradicting differences led us to interrogate the mechanism by which Mdm2 SNP309 regulates tumor susceptibility in a tissue-specific manner. The assessment of potential transcriptional regulators in ENCODE ChIP-seq database identified transcriptional repressor E2F6 as a possible negative regulator of MDM2 expression. Our data show that E2F6 protein is expressed at higher levels in skin keratinocytes of SNP309 mice as compared to lymphatic tissues. Furthermore, E2F6 binds and suppresses Mdm2 expression in cells harboring the SNP309G allele but not the SNP309T allele. Thus, the Mdm2 SNP309G allele exhibits tissue-specific regulation and differentially impacts cancer risk

Weighted norm inequalities for polynomial expansions associated to some measures with mass points

Fourier series in orthogonal polynomials with respect to a measure $\nu$ on $[-1,1]$ are studied when $\nu$ is a linear combination of a generalized Jacobi weight and finitely many Dirac deltas in $[-1,1]$. We prove some weighted norm inequalities for the partial sum operators $S_n$, their maximal operator $S^*$ and the commutator $[M_b, S_n]$, where $M_b$ denotes the operator of pointwise multiplication by b \in \BMO. We also prove some norm inequalities for $S_n$ when $\nu$ is a sum of a Laguerre weight on $\R^+$ and a positive mass on $0$

Pathways of development in the hillsides of Honduras: causes and implications for agricultural production, poverty, and sustainable resource use

Based on a survey of 48 communities in central Honduras, this paper identifies the major pathways of development that have been occurring in central Honduras since the mid-1970s, their causes and implications for agricultural productivity, natural resource sustainability, and poverty. Six pathways of development were identified: 1) basic grains expansion communities-where basic grains production is the dominant activity and increased basic grains production has occurred; 2) basic grains stagnation communities-where basic grains production is dominant but has stagnated or declined; 3) coffee expansion communities-where coffee production is important and has been increasing in importance; 4) horticultural expansion communities-where substantial adoption and expansion of horticultural crops has occurred; 5) forestry specialization communities-where forestry activities are important and basic grains production is stagnant or declining; and 6) nonfarm employment communities-where nonfarm employment is a major and increasing source of income. The findings imply that a “one-size-fits-all” approach to technical assistance is unlikely to be successful, since different approaches show promise in different pathways.Natural resources., Poverty., Technical assistance., Agricultural development., Honduras.,

Establishing a calibration for a microwave plasma continuous emissions monitor

Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Nuclear Engineering, 1998.Includes bibliographical references (leaves 53-54).In an effort to provide an accurate real-time continuous emissions monitor (CEM) for hazardous air-pollution metals as a viable option to EPA Method 29, a Microwave Induced Plasma (MIP) system is under development for real-time atomic emission spectroscopy in stack exhaust. This MIP-CEM has a nebulizer calibration subsystem attached to the sample line for real-time span calibration of the monitored metal concentrations. In order to quantify the amount of metal mass measured in the effluent flow, it is necessary to determine the analyte metal mass transport efficiency of the nebulizer system. A novel new approach to determine the nebulizer efficiency during plasma operation was tested in this thesis. A 0.1-mm tungsten filament attached to a 4- mm diameter alumina rod was used to introduce a known amount of mass into a nitrogen plasma at 0.5-cfm sample line flow in 6 different positions relative to the end of the sample line. The tungsten filament was heated by plasma radiation. These signals, obtained from the direct rod insertions, were then correlated to masses of metals aspirated by the nebulizer and drawn into the plasma through a quartz "T". The mass transport efficiency as a function of rod insertion position was calculated by dividing the correlated mass by the total mass aspirated by the nebulizer to achieve an identical signal. In the 4- inch long drift distance between the end of the sample line and the plasma sustaining waveguide, measurements from 0.5 inches away from the end of the sample line to 1.75 inches away, in 0.25-inch increments, were repeated, and the results tabulated. The efficiencies generally decreased as the rod was inserted closer to the plasma, with the efficiency extrapolated to 0.644 ± 0.153 % at the end of the sample line. The extrapolated value is in fair agreement with the efficiency used in the most recent field test conducted at Research Triangle Park in Raleigh-Durham, North Carolina. Initial tests at one insertion location of 1.75 in. were also done for a different nitrogen flow of 1.0 cfm and for air at 0.5 cfm. These initial tests are inconclusive, and more measurements are needed. Also, further testing is warranted for the determination of other factors, such as moisture, and the impact on the efficiency.by Guadalupe Jorge Flores III.S.M

Allantoin Crystal Formation in Bagrada hilaris (Burmeister) (Heteroptera: Pentatomidae) Females.

Bagrada hilaris is a polyphagous herbivore reported as an invasive pest in the United States. During the course of dissecting Burmeister hilaris unique crystals were observed in both the midgut and oviducts. Crystals were identified using X-ray diffraction techniques. Both acicular (i.e., needle-like, slender, and/or tapered) and cubic (i.e., cube shaped) crystals were observed in six of 75 individuals examined (8.0%). The crystals were mainly observed in females (6.7%), followed by males (1.3%) with no crystals observed in the minimal number of nymphs examined (0%). Crystals of both types were detected in the midgut and lateral oviducts of the females and midgut in males. The acicular crystals often appeared as distinct bundles when present in the midgut and oviducts. Crystals varied in size with the acicular crystals ranging from 0.12 mm to 0.5 mm in length although the cubic crystals ranged in length from 0.25 mm to over 1.0 mm with widths of ∼0.25 mm. The cubic crystals were identified as allantoin although the acicular crystals were most likely dl-allantoin in combination with halite. While allantoin in a soluble form is often found in insect tissues and excreta; being present as a crystal, especially in such a large form, is curious and raises some interesting questions. More research is warranted to further understand mechanisms associated with such crystal formation in B. hilaris and can lead to a better understanding of the excretory process in this species and the role allantoin plays in the elimination of excess nitrogen

Weighted Lp-boundedness of Fourier series with respect to generalized Jacobi weights

Let w be a generalized Jacobi weight on the interval [-1,1] and, for each function f, let Snf denote the n-th partial sum of the Fourier series of f in the orthogonal polynomials associated to w. We prove a result about uniform boundedness of the operators Sn in some weighted Lp spaces. The study of the norms of the kernels Kn related to the operators Sn allows us to obtain a relation between the Fourier series with respect to different generalized Jacobi weights