Cospectral Graphs and Digraphs

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135469/1/blms0321.pd

Prospectus, April 28, 1969

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Modulating Nucleus Oxygen Concentration by Altering Intramembrane Cholesterol Levels: Creating Hypoxic Nucleus in Oxic Conditions

We propose a novel mechanism by which cancer cells can modulate the oxygen concentration within the nucleus, potentially creating low nuclear oxygen conditions without the need of an hypoxic micro-environment and suited for allowing cancer cells to resist chemo- and radio-therapy. The cells ability to alter intra-cellular oxygen conditions depends on the amount of cholesterol present within the cellular membranes, where high levels of cholesterol can yield rigid membranes that slow oxygen diffusion. The proposed mechanism centers on the competition between (1) the diffusion of oxygen within the cell and across cellular membranes that replenishes any consumed oxygen and (2) the consumption of oxygen in the mitochondria, peroxisomes, endoplasmic reticulum (ER), etc. The novelty of our work centers around the assumption that the cholesterol content of a membrane can affect the oxygen diffusion across the membrane, reducing the cell ability to replenish the oxygen consumed within the cell. For these conditions, the effective diffusion rate of oxygen becomes of the same order as the oxygen consumption rate, allowing the cell to reduce the oxygen concentration of the nucleus, with implications to the Warburg Effect. The cellular and nucleus oxygen content is indirectly evaluated experimentally for bladder (T24) cancer cells and during the cell cycle, where the cells are initially synchronized using hydroxeaurea (HU) at the late G1-phase/early S-phase. The analysis of cellular and nucleus oxygen concentration during cell cycle is performed via (i) RT-qPCR gene analysis of hypoxia inducible transcription factors (HIF) and prolyl hydroxylases (PHD) and (ii) radiation clonogenic assay every 2 h, after release from synchronization. The HIF/PHD genes allowed us to correlate cellular oxygen with oxygen concentration in the nucleus that is obtained from the cells radiation response, where the amount DNA damage due to radiation is directly related to the amount of oxygen present in the nucleus. We demonstrate that during the S-phase cells can become hypoxic in the late S-phase/early G2-phase and therefore the radiation resistance increases 2- to 3-fold

Eligibility of Hon. Andrew W. Mellon, Secretary of the Treasury : report [and supplemental report] of the Committee on the Judiciary pursuant to S. Res. 2 relative to the tenure of office of heads of departments and the right of Andrew W. Mellon to hold the office of Secretary of the Treasury : together with the Minority views of Mr. Norris, Mr. Caraway, Mr. Walsh of Montana, and Mr. Blaine : the additional views of Mr. Blaine and Mr. Walsh of Montana, respectively : the Views of Mr. Borah, Mr. King, and Mr. Dill : and the Individual views of Mr. Ashurst

Title varies slightlyParts 1-6 ordered printed May 7, 1929. Pt. 7 submitted by Mr. Steiwer. Ordered printed June 4 (calendar day, June 12), 1929In 7 parts. Parts 1-6 in 1 vol., paged continuouslyMode of access: Internet