HeII Recombination Lines From the First Luminous Objects

The hardness of the ionizing continuum from the first sources of UV radiation plays a crucial role in the reionization of the intergalactic medium (IGM). While usual stellar populations have soft spectra, mini-quasars or metal-free stars with high effective temperatures may emit hard photons, capable of doubly ionizing helium and increasing the IGM temperature. Absorption within the source and in the intervening IGM will render the ionizing continuum of high-redshift sources inaccessible to direct observation. Here we show that HeII recombination lines from the first luminous objects are potentially detectable by the Next Generation Space Telescope. Together with measurements of the hydrogen Balmer alpha emission line, this detection can be used to infer the ratio of HeII to HI ionizing photons. A measurement of this ratio would shed light on the nature and emission mechanism of the first luminous sources, with important astrophysical consequences for the reheating and reionization of the IGM.Comment: ApJ published version. Due to an error in one of the references, the strength of the 1640 A line was underestimated in a previous version; this line is now brighter by a factor of 1

Deciphering the Role of Regulatory CD4 T Cells in Oral and Oropharyngeal Cancer : A Systematic Review

CO was supported by an Innes Will Scholarship, University of Aberdeen HotStart Summer Scholarship Scheme.Peer reviewedPublisher PD

Current Challenges in Prostate Cancer Management and the Rationale behind Targeted Focal Therapy

Among men, prostate cancer has a high prevalence, with relatively lower cancer-specific mortality risk compared to lung and colon cancer. Prostate-specific antigen (PSA) screening has increased prostate cancer awareness since its implementation as a screening tool almost 25 years ago, but, due to the largely indolent course of this disease and the unspecific nature of the PSA test, increased incidence has largely been associated with cancers that would not go on to cause death (clinically insignificant), leading to an overdiagnosis challenge and an ensuing overtreatment consequences. The overtreatment problem is exacerbated by the high risk of side effects that current treatment techniques have, putting patients' quality of life at risk with little or no survival benefit. The goals of this paper are to evaluate the rise, prevalence, and impact of the overdiagnosis and ensuing overtreatment problems, as well as highlight potential solutions. In this effort, a review of major epidemiological and screening studies, cancer statistics from the advent of prostate-specific antigen screening to the present, and reports on patient concerns and treatment outcomes was conducted to present the dominant factors that underlie current challenges in prostate cancer treatment and illuminate potential solutions

The Molecular Hydrogen Deficit in Gamma-Ray Burst Afterglows

Recent analysis of five gamma-ray burst (GRB) afterglow spectra reveal the absence of molecular hydrogen absorption lines, a surprising result in light of their large neutral hydrogen column densities and the detection of H$_2$ in similar, more local star-forming regions like 30 Doradus in the Large Magellanic Cloud (LMC). Observational evidence further indicates that the bulk of the neutral hydrogen column in these sight lines lies 100 pc beyond the progenitor and that H$_2$ was absent prior to the burst, suggesting that direct flux from the star, FUV background fields, or both suppressed its formation. We present one-dimensional radiation hydrodynamical models of GRB host galaxy environments, including self-consistent radiative transfer of both ionizing and Lyman-Werner photons, nine-species primordial chemistry with dust formation of H$_2$, and dust extinction of UV photons. We find that a single GRB progenitor is sufficient to ionize neutral hydrogen to distances of 50 - 100 pc but that a galactic Lyman-Werner background is required to dissociate the molecular hydrogen in the ambient ISM. Intensities of 0.1 - 100 times the Galactic mean are necessary to destroy H$_2$ in the cloud, depending on its density and metallicity. The minimum radii at which neutral hydrogen will be found in afterglow spectra is insensitive to the mass of the progenitor or the initial mass function (IMF) of its cluster, if present.Comment: 12 pages, 7 figures, accepted for Ap

On the Road to Immunotherapy : Prospects for Treating Head and Neck Cancers With Checkpoint Inhibitor Antibodies

Peer reviewedPublisher PD

The role of c-Jun in controlling the EPAC1-dependent induction of the SOCS3 gene in HUVECs

The cyclic AMP sensor, EPAC1, activates AP1-mediated transcription in HUVECs. Correspondingly, induction of the SOCS3 minimal promoter by EPAC1 requires a single AP1 site that constitutively binds phosphorylated (Ser63) c-Jun in DNA-pull-down assays. c-Jun (Ser63) becomes further phosphorylated following cyclic AMP stimulation and specific activation of protein kinase A (PKA), but not through selective activation of EPAC1. Moreover, despite a requirement for c-Jun for SOCS3 induction in fibroblasts, phospho-null c-Jun (Ser63/73Ala) had little effect on SOCS3 induction by cyclic AMP in HUVECs. AP1 activation and SOCS3 induction by EPAC1 in HUVECs therefore occur independently of c-Jun phosphorylation on Ser63

Unmasking the interplay between mTOR and Nox4: novel insights into the mechanism connecting diabetes and cancer

Cancer was recently annexed to diabetic complications. Furthermore, recent studies suggest that cancer can increase the risk of diabetes. Consequently, diabetes and cancer share many risk factors, but the cellular and molecular pathways correlating diabetes and colon and rectal cancer (CRC) remain far from understood. In this study, we assess the effect of hyperglycemia on cancer cell aggressiveness in human colon epithelial adenocarcinoma cells in vitro and in an experimental animal model of CRC. Our results show that Nox (NADPH oxidase enzyme) 4-induced reactive oxygen species (ROS) production is deregulated in both diabetes and CRC. This is paralleled by inactivation of the AMPK and activation of the mammalian target of rapamycin (mTOR) C1 signaling pathways, resulting in 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) accumulation, induction of DNA damage, and exacerbation of cancer cell aggressiveness, thus contributing to the genomic instability and predisposition to increased tumorigenesis in the diabetic milieu. Pharmacologic activation of AMPK, inhibition of mTORC1, or blockade of Nox4 reduce ROS production, restore the homeostatic signaling of 8-oxoguanine DNA glycosylase/8-oxodG, and lessen the progression of CRC malignancy in a diabetic milieu. Taken together, our results identify the AMPK/mTORC1/Nox4 signaling axis as a molecular switch correlating diabetes and CRC. Modulating this pathway may be a strategic target of therapeutic potential aimed at reversing or slowing the progression of CRC in patients with or without diabetes.-Mroueh, F. M., Noureldein, M., Zeidan, Y. H., Boutary, S., Irani, S. A. M., Eid, S., Haddad, M., Barakat, R., Harb, F., Costantine, J., Kanj, R., Sauleau, E.-A., Ouhtit, A., Azar, S. T., Eid, A. H., Eid, A. A. Unmasking the interplay between mTOR and Nox4: novel insights into the mechanism connecting diabetes and cancer.Scopu