Cell cycle specific radiosensitisation by the disulfiram and copper complex

The disulfiram and copper complex (DSF:Cu) has emerged as a potent radiosensitising anti-cancer agent. The ability of copper to stabilise DSF in a planar conformation and to inhibit DNA replication enzymes stimulated our investigation of the effect of DSF:Cu on cell cycle regulation. Flow cytometry and immunoblotting were used to assess the effect of DSF:Cu on cell cycle progression of the neuroblastoma cell line SK-N-BE(2c) and the glioma cell line UVW. Treatment with 0.1 and 0.3 μM DSF:Cu inhibited DNA synthesis in SK-N-BE(2c) and UVW cells, respectively. The increased potency of ionising radiation treatment induced by DSF:Cu and/or gemcitabine was determined by clonogenic assay. Treatment with 0.3 μM DSF:Cu resulted in greater radiation kill, exemplified by dose enhancement factor values of 2.64 and 2.84 in SKN-BE(2c) and UVW cells, respectively. Although DSF:Cu failed to sensitise S phase cells to irradiation, we observed that DSF:Cu radiosensitisation was potentiated by the S phase-specific cytotoxic drug gemcitabine. The efficacy of the combination treatment consisting of DSF:Cu, gemcitabine and ionising radiation was scheduledependent. Together, these results describe cell cycle specific radiosensitisation by DSF:Cu. The well-established toxicity profiles of DSF and gemcitabine should facilitate their evaluation as a combination treatment in patients undergoing radiotherapy

A new approach to the modeling of SHS reactions: Combustion synthesis of transition metal aluminides

A recently developed numerical simulation of self-propagating high-temperature synthesis (SHS) using an approach based on microscopic reaction mechanisms and utilizing appropriate physical parameters is applied to the SHS of a fairly large group of transition metal aluminides. The model was utilized to analyze temperature profiles and wave instability and the results were interpreted in terms of chemical and thermal effects. The effect of the particle size of the transition metal, the porosity of the reactant mixtures, and the dilution was iinvestigated. The results are in good agreement with available experimental data

Nanoscale effects on the ionic conductivity of highly doped bulk nanometric cerium oxide

Nanometric ceria powders doped with 30 mol % samaria are consolidated by a high-pressure spark plasma sintering (HP-SPS) method to form > 99 % dense samples with a crystallite size as small as 16.5 nm. A conductivity dependence on grain size was noted: when the grain size was less than 20 nm, only one semicircle in the AC impedance spectra was observed and was attributed to bulk conductivity. In contrast to previous observations on pure ceria, the disappearance of the grain-boundary blocking effect is not associated with mixed conductivity. With annealing and concomitant grain growth, the samples show the presence of a grain-boundary effect

ATP synthase: evolution, energetics, and membrane interactions

The synthesis of ATP, life's 'universal energy currency', is the most prevalent chemical reaction in biological systems, and is responsible for fueling nearly all cellular processes, from nerve impulse propagation to DNA synthesis. ATP synthases, the family of enzymes that carry out this endless task, are nearly as ubiquitous as the energy-laden molecule they are responsible for making. The F-type ATP synthase (F-ATPase) is found in every domain of life, and is believed to predate the divergence of these lineages over 1.5 billion years ago. These enzymes have therefore facilitated the survival of organisms in a wide range of habitats, ranging from the deep-sea thermal vents to the human intestine. In this review, we present an overview of the current knowledge of the structure and function of F-type ATPases, highlighting several adaptations that have been characterized across taxa. We emphasize the importance of studying these features within the context of the enzyme's particular lipid environment: Just as the interactions between an organism and its physical environment shape its evolutionary trajectory, ATPases are impacted by the membranes within which they reside. We argue that a comprehensive understanding of the structure, function, and evolution of membrane proteins -- including ATP synthase -- requires such an integrative approach.Comment: Review article; 29 pages, 6 figures/1 tabl

Euclid preparation TBD. The effect of baryons on the Halo Mass Function

The Euclid photometric survey of galaxy clusters stands as a powerful cosmological tool, with the capacity to significantly propel our understanding of the Universe. Despite being sub-dominant to dark matter and dark energy, the baryonic component in our Universe holds substantial influence over the structure and mass of galaxy clusters. This paper presents a novel model to precisely quantify the impact of baryons on galaxy cluster virial halo masses, using the baryon fraction within a cluster as proxy for their effect. Constructed on the premise of quasi-adiabaticity, the model includes two parameters calibrated using non-radiative cosmological hydrodynamical simulations and a single large-scale simulation from the Magneticum set, which includes the physical processes driving galaxy formation. As a main result of our analysis, we demonstrate that this model delivers a remarkable one percent relative accuracy in determining the virial dark matter-only equivalent mass of galaxy clusters, starting from the corresponding total cluster mass and baryon fraction measured in hydrodynamical simulations. Furthermore, we demonstrate that this result is robust against changes in cosmological parameters and against varying the numerical implementation of the sub-resolution physical processes included in the simulations. Our work substantiates previous claims about the impact of baryons on cluster cosmology studies. In particular, we show how neglecting these effects would lead to biased cosmological constraints for a Euclid-like cluster abundance analysis. Importantly, we demonstrate that uncertainties associated with our model, arising from baryonic corrections to cluster masses, are sub-dominant when compared to the precision with which mass-observable relations will be calibrated using Euclid, as well as our current understanding of the baryon fraction within galaxy clusters.Comment: 18 pages, 10 figures, 4 tables, 1 appendix, abstract abridged for arXiv submissio

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection