Evasion of anti-growth signaling: a key step in tumorigenesis and potential target for treatment and prophylaxis by natural compounds

The evasion of anti-growth signaling is an important characteristic of cancer cells. In order to continue to proliferate, cancer cells must somehow uncouple themselves from the many signals that exist to slow down cell growth. Here, we define the anti-growth signaling process, and review several important pathways involved in growth signaling: p53, phosphatase and tensin homolog (PTEN), retinoblastoma protein (Rb), Hippo, growth differentiation factor 15 (GDF15), AT-rich interactive domain 1A (ARID1A), Notch, insulin-like growth factor (IGF), and Krüppel-like factor 5 (KLF5) pathways. Aberrations in these processes in cancer cells involve mutations and thus the suppression of genes that prevent growth, as well as mutation and activation of genes involved in driving cell growth. Using these pathways as examples, we prioritize molecular targets that might be leveraged to promote anti-growth signaling in cancer cells. Interestingly, naturally-occurring phytochemicals found in human diets (either singly or as mixtures) may promote anti-growth signaling, and do so without the potentially adverse effects associated with synthetic chemicals. We review examples of naturally-occurring phytochemicals that may be applied to prevent cancer by antagonizing growth signaling, and propose one phytochemical for each pathway. These are: epigallocatechin-3-gallate (EGCG) for the Rb pathway, luteolin for p53, curcumin for PTEN, porphyrins for Hippo, genistein for GDF15, resveratrol for ARID1A, withaferin A for Notch and diguelin for the IGF1-receptor pathway. The coordination of anti-growth signaling and natural compound studies will provide insight into the future application of these compounds in the clinical setting

Numerical tools for atomistic simulations.

The final report for a Laboratory Directed Research and Development project entitled 'Parallel Atomistic Computing for Failure Analysis of Micromachines' is presented. In this project, atomistic algorithms for parallel computers were developed to assist in quantification of microstructure-property relations related to weapon micro-components. With these and other serial computing tools, we are performing atomistic simulations of various sizes, geometries, materials, and boundary conditions. These tools provide the capability to handle the different size-scale effects required to predict failure. Nonlocal continuum models have been proposed to address this problem; however, they are phenomenological in nature and are difficult to validate for micro-scale components. Our goal is to separately quantify damage nucleation, growth, and coalescence mechanisms to provide a basis for macro-scale continuum models that will be used for micromachine design. Because micro-component experiments are difficult, a systematic computational study that employs Monte Carlo methods, molecular statics, and molecular dynamics (EAM and MEAM) simulations to compute continuum quantities will provide mechanism-property relations associated with the following parameters: specimen size, number of grains, crystal orientation, strain rates, temperature, defect nearest neighbor distance, void/crack size, chemical state, and stress state. This study will quantify sizescale effects from nanometers to microns in terms of damage progression and thus potentially allow for optimized micro-machine designs that are more reliable and have higher fidelity in terms of strength. In order to accomplish this task, several atomistic methods needed to be developed and evaluated to cover the range of defects, strain rates, temperatures, and sizes that a material may see in micro-machines. Therefore we are providing a complete set of tools for large scale atomistic simulations that include pre-processing of realistic material configurations, processing under different environments, and post-processing with appropriate continuum quantities. By running simulations with these tools, we are able to determine size scale effects that correlate microstructure and defect configurations with mechanical properties of materials

Conceptual Design of the Modular Detector and Readout System for the CMB-S4 survey experiment

We present the conceptual design of the modular detector and readout system for the Cosmic Microwave Background Stage 4 (CMB-S4) ground-based survey experiment. CMB-S4 will map the cosmic microwave background (CMB) and the millimeter-wave sky to unprecedented sensitivity, using 500,000 superconducting detectors observing from Chile and Antarctica to map over 60 percent of the sky. The fundamental building block of the detector and readout system is a detector module package operated at 100 mK, which is connected to a readout and amplification chain that carries signals out to room temperature. It uses arrays of feedhorn-coupled orthomode transducers (OMT) that collect optical power from the sky onto dc-voltage-biased transition-edge sensor (TES) bolometers. The resulting current signal in the TESs is then amplified by a two-stage cryogenic Superconducting Quantum Interference Device (SQUID) system with a time-division multiplexer to reduce wire count, and matching room-temperature electronics to condition and transmit signals to the data acquisition system. Sensitivity and systematics requirements are being developed for the detector and readout system over a wide range of observing bands (20 to 300 GHz) and optical powers to accomplish CMB-S4's science goals. While the design incorporates the successes of previous generations of CMB instruments, CMB-S4 requires an order of magnitude more detectors than any prior experiment. This requires fabrication of complex superconducting circuits on over 10 square meters of silicon, as well as significant amounts of precision wiring, assembly and cryogenic testing.Comment: 25 pages, 15 figures, presented at and published in the proceedings of SPIE Astronomical Telescopes and Instrumentation 202

Pollutant formation and emissions from cement kiln stack using a solid recovered fuel from municipal solid waste

The thermal decomposition of a Solid Recovered Fuel (SRF) has been studied by two techniques. First, laboratory-scale experiments were performed in a horizontal furnace in which different atmospheres are studied to analyze the dioxins and furans (PCDD/Fs) evolved from the decomposition of the material. Sulfur presence is revealed to be important in PCDD/Fs formation. In the second technique, the emission of various pollutants (PAHs, PCDD/Fs, metals, acid gases …) were determined in a cement kiln fed on different proportions of SRF material, and where a maximum feed rate of 15000 kg SRF/h was achieved. In the laboratory furnace the dioxin toxicity revealed a maximum when the amount of oxygen in the atmosphere increased until approximately stoichiometric conditions. In the cement kiln, all emitted pollutants are under the legal limits. No correlation between SRF input and metal emission was observed.Support for this work was provided by CEMEX ESPANA, S.A., a company owned by the CEMEX group (http://www.cemex.com). Authors acknowledge the financial support for this work provided by PROMETEO/2009/043/FEDER and ACOMP2010/075 of Generalitat Valenciana (Spain) and CTQ2008-05520 (Spanish MCI)

Comparison between emissions from the pyrolysis and combustion of different wastes

A comparison between different emission rates of various pollutants obtained from various wastes is presented. The studied wastes were the following: polyethylene (PE), tyres, sewage sludges, polyvinyl chloride (PVC), cotton textiles, polyester textiles, meat and bone meals (MBMs), varnish wastes, olive oil solid waste (pomace), waste lube oils and paper waste. The decomposition of these wastes was studied in a horizontal laboratory scale reactor under fuel-rich conditions, and the analysis of the pollutants evolved comprised several compounds such as light hydrocarbons, polyaromatic hydrocarbons (PAHs) and polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs). From the studied wastes, a general behaviour was deduced regarding the evolution of semi-volatile compounds with the increase of temperature, both in pyrolysis and combustion. The results showed that the emissions of some compounds decreased with increasing oxygen ratio. Compounds with this behaviour were mainly volatile hydrocarbons, which were consumed in presence of oxygen. In addition, compounds with oxidized structure were present a maximum with oxygen ratio. Intermediate compounds with very high resistance to the oxygen under the working conditions increased continuously in concentration when the oxygen ratio increased. With reference to behaviour versus temperature there were compounds whose yields decreased with increasing temperature, such as volatile hydrocarbons and semi-volatile compounds. Also some pollutants are promoted at intermediate temperatures, e.g. light hydrocarbons, semi-volatile compounds, many monoaromatic compounds and many polyaromatic hydrocarbons.Financial support from Generalitat Valenciana (Spain) project GV06/069, and the Spanish MCT research project CTQ2005-05262/PPQ