Radiation Sensitization of Breast Cancer Cells by Vitamin D Through the Promotion of Autophagic Cell Death

Radiation therapy is a widely used tool in cancer therapy and is frequently offered as the first line of treatment for cancers of the breast. While radiotherapy is often initially effective in killing tumor cells or suppressing their growth, there are factors that confer tumor cell resistance to irradiation. Development of resistance may lead to disease recurrence despite the use of surgery, chemotherapy and radiation therapy. A primary goal of the studies in Dr. Gewirtz’s laboratory is to develop strategies to overcome resistance to radiation (and chemotherapy) in breast cancer, with the ultimate goal of preventing or attenuating disease recurrence. One of these approaches involves combining the active form of vitamin D, 1,25-di hydroxy vitamin D3 or its analogs with radiotherapy. Our proposed studies were designed to build upon and extend previous work from this laboratory focused on determining the nature of cell death when vitamin D3 is combined with ionizing radiation in breast tumor cells. Studies were extended to the wild type p53, estrogen receptor positive, ZR-75-1 breast cancer cell line. We were able to validate that vitamin D3 does in fact, sensitize ZR-75-1 breast cancer cells to radiation therapy and substantiate that autophagy is the mode of sensitization by vitamin D3. Interestingly, our experimental system demonstrated that autophagy can actually have dual roles. Specifically, inhibition of autophagy both enhanced sensitivity to radiation and attenuated radiation sensitization by 1,25D3. Moreover, this experimental model proved to be a useful tool in trying to distinguish the factors involved in cytoprotective and cytotoxic autophagy, as we were able to demonstrate a potential role of 5\u27 adenosine monophosphate-activated protein kinase in the sensitization of breast tumor cells to radiation by vitamin D3 as well as cytotoxic autophagy

MOTHER AND CHILD RESIDENTIAL TREATMENT FROM AN ADULT CHILD PERSPECTIVE: THE FORGOTTEN VOICES

These days most everyone can say that they know someone who has been impacted by substance abuse and today’s society is very familiar with the fact that it can wreak havoc on families. There has been a significant amount of research devoted to finding not only the best practices to treat families who are impacted by the disease of addiction but there has also been a great deal of attention focused on the adult perspective on these services once they have been received. Where the research is definitely lacking is how the children involved with the services perceive their own involvement. How are their lives impacted by being involved in treatment with their caretaker? The children seem to be the forgotten voices in this scenario. This study focuses on the adult/child perspective of children who have experienced at least one residential treatment episode with their mothers. The sample came from a long-term residential drug treatment facility that is primary focused on treating families impacted by substance abuse. These adult children experienced treatment with their mothers before they were 12 years old. They will share their perspectives on this experience

The measurement of homonegative reactions with physiological and subjective reports

A proposal to present a paper on the physiological measurement of homonegativit

Effect of Noise on Patterns Formed by Growing Sandpiles

We consider patterns generated by adding large number of sand grains at a single site in an abelian sandpile model with a periodic initial configuration, and relaxing. The patterns show proportionate growth. We study the robustness of these patterns against different types of noise, \textit{viz.}, randomness in the point of addition, disorder in the initial periodic configuration, and disorder in the connectivity of the underlying lattice. We find that the patterns show a varying degree of robustness to addition of a small amount of noise in each case. However, introducing stochasticity in the toppling rules seems to destroy the asymptotic patterns completely, even for a weak noise. We also discuss a variational formulation of the pattern selection problem in growing abelian sandpiles.Comment: 15 pages,16 figure

Superconformal operators in Yang-Mills theories on the light-cone

We employ the light-cone superspace formalism to develop an efficient approach to constructing superconformal operators of twist two in Yang-Mills theories with N=1,2,4 supercharges. These operators have an autonomous scale dependence to one-loop order and determine the eigenfunctions of the dilatation operator in the underlying gauge theory. We demonstrate that for arbitrary N the superconformal operators are given by remarkably simple, universal expressions involving the light-cone superfields. When written in components field, they coincide with the known results obtained by conventional techniques.Comment: 29 pages, Late

Globally conformal invariant gauge field theory with rational correlation functions

Operator product expansions (OPE) for the product of a scalar field with its conjugate are presented as infinite sums of bilocal fields V_k (x_1, x_2) of dimension (k,k). For a {\it globally conformal invariant} (GCI) theory we write down the OPE of V_k into a series of {\it twist} (dimension minus rank) 2k symmetric traceless tensor fields with coefficients computed from the (rational) 4-point function of the scalar field. We argue that the theory of a GCI hermitian scalar field L(x) of dimension 4 in D = 4 Minkowski space such that the 3-point functions of a pair of L's and a scalar field of dimension 2 or 4 vanish can be interpreted as the theory of local observables of a conformally invariant fixed point in a gauge theory with Lagrangian density L(x).Comment: 32 pages, LATEX, amssym

General relativistic polarized radiative transfer: building a dynamics-observations interface

The rising amount of polarized observations of relativistic sources requires the correct theory for proper model fitting. The equations for general relativistic (GR) polarized radiative transfer are derived starting from the Boltzmann equation and basic ideas of general relativity. The derivation is aimed at providing a practical guide to reproducing the synchrotron part of radio & sub-mm emission from low luminosity active galactic nuclei (LLAGNs), in particular Sgr A*, and jets. The recipe for fast exact calculation of cyclo-synchrotron emissivities, absorptivities, Faraday rotation and conversion coefficients is given for isotropic particle distributions. The multitude of physical effects influencing simulated spectrum is discussed. The application of the prescribed technique is necessary to determine the black hole (BH) spin in LLAGNs, constraining it with all observations of total flux, linear and circular polarization fractions, and electric vector position angle as functions of the observed frequency.Comment: 9 pages, 3 figures, accepted by MNRA

Psychedelics Promote Structural and Functional Neural Plasticity.

Atrophy of neurons in the prefrontal cortex (PFC) plays a key role in the pathophysiology of depression and related disorders. The ability to promote both structural and functional plasticity in the PFC has been hypothesized to underlie the fast-acting antidepressant properties of the dissociative anesthetic ketamine. Here, we report that, like ketamine, serotonergic psychedelics are capable of robustly increasing neuritogenesis and/or spinogenesis both in vitro and in vivo. These changes in neuronal structure are accompanied by increased synapse number and function, as measured by fluorescence microscopy and electrophysiology. The structural changes induced by psychedelics appear to result from stimulation of the TrkB, mTOR, and 5-HT2A signaling pathways and could possibly explain the clinical effectiveness of these compounds. Our results underscore the therapeutic potential of psychedelics and, importantly, identify several lead scaffolds for medicinal chemistry efforts focused on developing plasticity-promoting compounds as safe, effective, and fast-acting treatments for depression and related disorders

Bremsstrahlung in intermediate-energy nucleon reactions within an effective one-boson exchange model

Within a covariant effective one-boson exchange model for the $T$ matrix of $NN$ interactions we present detailed calculations of bremsstrahlung cross sections for proton - proton and proton - neutron reactions at beam energies in the 1 GeV region. Besides pure bremsstrahlung processes we consider photons from $\Delta$ decays and contributions from the $\eta \to \gamma \gamma$ process. At beam energies above 700 MeV the $\Delta$ decay channel dominates the spectra at large photon energies, where the interference between non-resonance processes and the $\Delta$ decay channel becomes also important. Low energy photons stem from pure bremsstrahlung processes. The available experimental data at 730 MeV beam energy is well described. We extrapolate the model down to 280 MeV, where more detailed experimental data exist, and find agreement with angular distributions.Comment: 20 pages with 10 figures, to be published in Nucl. Phys.