Preclinical evaluation of the antineoplastic action of 5-aza-2'-deoxycytidine and different histone deacetylase inhibitors on human Ewing's sarcoma cells

<p>Abstract</p> <p>Background</p> <p>Most patients with advanced Ewing's sarcoma (EWS) respond poorly to conventional chemotherapy, indicating the need for new treatment approaches. Epigenetic events, such as promoter hypermethylation and chromatin histone deacetylation, silence the expression of tumor suppressor genes (TSGs) and play an important role in tumorigenesis. These epigenetic changes can be reversed by using 5-aza-2'-deoxycytidine (5AZA-CdR), a potent inhibitor of DNA methylation, in combination with an inhibitor of histone deacetylase (HDAC).</p> <p>Results</p> <p>Here, we used a clonogenic assay to evaluate the <it>in vitro </it>antineoplastic activity of 5AZA-CdR in combination with different HDAC inhibitors on EWS cells. We observed that the HDAC inhibitors, MS-275, trichostatin-A, phenylbutyrate, LAQ824 and depsipeptide, enhanced the antineoplastic action of 5AZA-CdR on EWS cells. The combination of 5AZA-CdR and MS-275 showed marked synergy, and was correlated with significant reactivation of the expression of two TSGs, E-cadherin and tumor suppressor lung cancer-1 (TSLC1), in a EWS cell line.</p> <p>Conclusion</p> <p>These results suggest the value of future clinical studies investigating the combination of 5AZA-CdR and MS-275 in patients with advanced EWS.</p

Azithromycin use in paediatrics: A practical overview

Azithromycin is an antibiotic that is commonly prescribed for upper and lower respiratory tract infections in children. While it has proven benefits, some concerns regarding azithromycin use have arisen in recent years. This practice point considers azithromycin therapy for acute respiratory infections in otherwise healthy children. Pharmacokinetics, spectrum of activity, the problem of resistant bacteria and clinical aspects are considered, along with recommendations for use and contraindications. Azithromycin should be avoided in patients with a significant risk of bacteremia. It is associated with pneumococcal resistance and, with stated exceptions, is generally not recommended for the treatment of acute pharyngitis, acute otitis media or pneumococcal community-acquired pneumonia in the paediatric population. © Canadian Paediatric Society 2013

Incommensurate Transverse Anisotropy Induced by Disorder and Spin-Orbit-Vibron Coupling in Mn12-acetate

It has been shown within density-functional theory that in Mn$_{12}$-acetate there are effects due to disorder by solvent molecules and a coupling between vibrational and electronic degrees of freedom. We calculate the in-plane principal axes of the second-order anisotropy caused by the second effect and compare them with those of the fourth-order anisotropy due to the first effect. We find that the two types of the principal axes are not commensurate with each other, which results in a complete quenching of the tunnel-splitting oscillation as a function of an applied transverse field.Comment: Will be presented at MMM conference 200

Soylent: A Word Processor with a Crowd Inside

This paper introduces architectural and interaction patterns for integrating crowdsourced human contributions directly into user interfaces. We focus on writing and editing, com-plex endeavors that span many levels of conceptual and pragmatic activity. Authoring tools offer help with prag-matics, but for higher-level help, writers commonly turn to other people. We thus present Soylent, a word processing interface that enables writers to call on Mechanical Turk workers to shorten, proofread, and otherwise edit parts of their documents on demand. To improve worker quality, we introduce the Find-Fix-Verify crowd programming pat-tern, which splits tasks into a series of generation and re-view stages. Evaluation studies demonstrate the feasibility of crowdsourced editing and investigate questions of relia-bility, cost, wait time, and work time for edits.National Science Foundation (U.S.) (Grant No. IIS-0712793

Magnetic ordering, electronic structure and magnetic anisotropy energy in the high-spin Mn10_{10} single molecule magnet

We report the electronic structure and magnetic ordering of the single molecule magnet [Mn$_{10}$O$_{4}$(2,2'-biphenoxide)$_{4}$Br$_{12}$]$^{4-}$ based on first-principles all-electron density-functional calculations. We find that two of the ten core Mn atoms are coupled antiferromagnetically to the remaining eight, resulting in a ferrimagnetic ground state with total spin S=13. The calculated magnetic anisotropy barrier is found to be 9 K in good agreement with experiment. The presence of the Br anions impact the electronic structure and therefore the magnetic properties of the 10 Mn atoms. However, the electric field due to the negative charges has no significant effect on the magnetic anisotropy.Comment: 4 pages, submitted to PR

A New Era in Extragalactic Background Light Measurements: The Cosmic History of Accretion, Nucleosynthesis and Reionization

(Brief Summary) What is the total radiative content of the Universe since the epoch of recombination? The extragalactic background light (EBL) spectrum captures the redshifted energy released from the first stellar objects, protogalaxies, and galaxies throughout cosmic history. Yet, we have not determined the brightness of the extragalactic sky from UV/optical to far-infrared wavelengths with sufficient accuracy to establish the radiative content of the Universe to better than an order of magnitude. Among many science topics, an accurate measurement of the EBL spectrum from optical to far-IR wavelengths, will address: What is the total energy released by stellar nucleosynthesis over cosmic history? Was significant energy released by non-stellar processes? Is there a diffuse component to the EBL anywhere from optical to sub-millimeter? When did first stars appear and how luminous was the reionization epoch? Absolute optical to mid-IR EBL spectrum to an astrophysically interesting accuracy can be established by wide field imagingat a distance of 5 AU or above the ecliptic plane where the zodiacal foreground is reduced by more than two orders of magnitude.Comment: 7 pages; Science White Paper for the US Astro 2010-2020 Decadal Survey. If interested in further community-wide efforts on this topic please contact the first autho