Genetic polymorphisms in the folate metabolizing pathway and breast cancer survival.

Genes in folate metabolizing pathway are responsible for modulating key enzymes in folate metabolisms necessary for DNA synthesis and repair and influence DNA methylation. Irregularity in DNA methylation may modify tumor phenotype response to chemotherapy and abnormal DNA synthesis, and repair may lead to carcinogenesis. This dissertation project tested the hypothesis that the key genes in the folate metabolizing pathway, namely Methylenetetrahydrofolate reductase (MTHFR) , betaine-homocysteinemethyltransferase (BHMT) , 5-methyltetrahydrofolate-homocysteine (MTR), 5-methyltetrahydrofolate-homocysteine methyltransferase reductase (MTRR) , and serine hydroxymethyltransferase (SHMT1) and folate receptor 1 (FOLR1) influences all- cause and breast cancer-specific mortality and the association between the genes in the folate metabolizing pathway and breast cancer-specific survival is modified by chemotherapy and estrogen receptor (ER) status. Gene-gene interactions among the genes in the folate metabolizing pathway were also tested in this study. Data for this study were obtained from the New Mexico site of the Health, Eating, Activity, and Lifestyle (HEAL) Study for 446 incident primary breast cancer cases (stage 0 - IIIA). Over 11.46 years of follow-up, there were 67 deaths; 22 due to breast cancer. In the Cox proportional hazards analysis, women who carried at least one variant allele for MTRR G66A polymorphism had statistically significant inverse associations with all- cause (Hazard Ratio [HR]: 0.51; 95% confidence interval [CI]: 0.3-0.8; p-value \u3c 0.01) and breast cancer-specific mortality (HR: 0.40; 95% CI: 0.2-0.9; p-value \u3c 0.01). There were no statistically significant interactions with chemotherapy or ER status. Synergistic multiplicative interaction was observed between BHMT A742G and FOLR1 G606A polymorph isms in predicting breast cancer-specific mortality (p for interaction: 0.03). In this sample, there was antagonistic multiplicative interaction between MTRR G66A and MTHFR C677T polymorphisms in predicting breast cancer-specific mortality (p for interaction: 0.08). These results should be further explored in larger cohorts and in clinical populations

The challenges of hypertext writers : a case study

This thesis examines the challenges of hypertext writers with respect to six aspects of writing: authority, audience, organization, document design, style and multimedia use. This study is primarily based on the theories presented in the three books-Jay David Bolter\u27s Writing Space, George P. Landow\u27s Hypertext 2.0 and Ilana Snyder\u27s Hypertext. Information is collected by means of structured interviews from Bolter and Snyder. This study reveals that the hypertext medium does pose challenges to writers who are used to writing for the print medium and are new to the hypertext medium. Hypertext environment requires that the writer should either possess multiple, diverse skills or work collaboratively. Primary causes of challenges are newness of the medium and lack of education emphasizing visual literacy. Moreover, the challenges point towards the necessity of a new kind of literacy that includes not only visual literacy, but also multimedia literacy. A new rhetoric that addresses both a document\u27s visual design and structural design is very necessary

Self-assembling Modified β -cyclodextrin Conjugated siRNA Nanoparticles and Liposomal siRNA Efficiently Knock Down the Mutant Huntingtin Gene in a Modified PC-12 Cell Line

Purpose: To formulate and characterize liposomal siRNA (LP-siRNA) and cationic β-cyclodextrin siRNA (CD-siRNA) nanoparticle complexes and evaluate their efficacy in knockdown of mutant Huntingtin protein (mHtt) in a modified PC-12 cell line

Curcuminoid in Nanoemulsion Formulations Cause Enhanced Cell Death in the HeLa Cancer Cell Culture Model

Purpose: To formulate and characterize curcuminoid (insoluble chemoprevention agent) loaded nanoemulsions and evaluate their cytotoxicity in HeLa cells

Novel Targeting Approaches of Nanoparticles for Anticancers Drug Delivery: A Focused Review

Nanoparticles have presented a new paradigm in anticancer drug delivery to reduce adverse effects and improve therapeutic outcomes. Nanoparticle surface properties and morphology significantly affect the drug delivery to tumors while passive targeting. Conjugations with hyaluronic acid, transferrin and aptamers have shown to be effective in active targeting of anticancer drugs to tumor tissues. This review presents an overview of some credible techniques of passive and active drug delivery to tumors

Vegetation composition and assessment of phytotoxicity in a paper mill dumpsite

The solid waste dumpsites of pulp and paper industries are prone to be turned into degraded lands due to the loss of vegetation cover. Such sites often possess drought, salinity and pH stresses as well as heavy metal contamination. Restoration of top soil by creating vegetation cover has proved to be the most sustainable approach to check land degradation. Therefore, to find some stress-tolerant species capable of creating vegetation cover in paper mill dumpsites, a vegetation composition study was conducted in a paper mill dumpsite. A total of seven plant species viz., Calotropis gigantea (L.) Dryand., Chromolaena odorata (L.) R.M. King & H. Rob, Mikania scandens (L.) Willd., R. communis L., Rotheca serrata (L.) Steane & Mabb., Senna sophera (L.) Roxb. and Solanum myriacanthum Dunal were found. To correlate the existence of these plants with stress condition of soil, the level of phytotoxicity in the dumpsite was assessed by studying seed germination status, proline accumulation, leaf relative water content (RWC), leaf pH, total chlorophyll content and ascorbic acid level of Ricinus communis as bioassay indices. The significantly lower percentage of seed germination in dumpsite soil, compared to control, revealed the phytotoxic nature of the soil of the dumpsite. The significantly higher level of proline, RWC, total chlorophyll and ascorbic acid in plant leaves from dumpsites than from the control soils indicated considerable stress in the dumpsite. Soil physicochemical and nutrient status analyses substantiated with the bioassay results. Despite apparent phytotoxicity, the presence of certain plant species in the dumpsite indicated their inherent stress tolerance capability to be prospected

Constraining primordial black hole masses through f(R)f(R) gravity scalarons in Big Bang Nucleosynthesis

Big Bang Nucleosynthesis (BBN) is a strong probe for constraining new physics including gravitation. $f(R)$ gravity theory is an interesting alternative to general relativity which introduces additional degrees of freedom known as scalarons. In this work we demonstrate the existence of black hole solutions in $f(R)$ gravity and develop a relation between scalaron mass and black hole mass. We have used observed bound on the freezeout temperature to constrain scalaron mass range by modifying the cosmic expansion rate at the BBN epoch. The mass range of primordial black holes (PBHs) which are astrophysical dark matter candidates is deduced. The range of scalaron mass which does not spoil the BBN era is found to be $10^{-16}-10^4 \text{ eV}$. The scalaron mass window $10^{-16}-10^{-14}\text{ eV}$ is consistent with the $f(R)$ gravity PPN parameter derived from solar system experiments. The PBH mass range is obtained as $10^6-10^{-14}\text{ }M_{\odot}$. Scalarons constrained by BBN are also eligible to accommodate axion like dark matter particles. Estimation of deuterium (D) fraction and relative D+$^3$He abundance in the $f(R)$ gravity scenario shows that the BBN history mimics that of general relativity. While the PBH mass range is eligible for non-baryonic dark matter, the BBN bounded scalarons provide with an independent strong field test of $f(R)$ gravity.Comment: 24 pages, 3 figures, comments are welcome