Arizona\u27s Vulnerable Populations

Arizona’s vulnerable populations are struggling on a daily basis but usually do so in silence, undetected by traditional radar and rankings, often unaware themselves of their high risk for being pushed or pulled into a full crisis. Ineligible for financial assistance under strict eligibility guidelines, they don’t qualify as poor because vulnerable populations are not yet in full crisis. To be clear, this report is not about the “poor,” at least not in the limited sense of the word. It is about our underemployed wage earners, our single-parent households, our deployed or returning military members, our under-educated and unskilled workforce, our debt-ridden neighbors, our uninsured friends, our family members with no savings for an emergency, much less retirement

Principles of genetic circuit design

Cells navigate environments, communicate and build complex patterns by initiating gene expression in response to specific signals. Engineers seek to harness this capability to program cells to perform tasks or create chemicals and materials that match the complexity seen in nature. This Review describes new tools that aid the construction of genetic circuits. Circuit dynamics can be influenced by the choice of regulators and changed with expression 'tuning knobs'. We collate the failure modes encountered when assembling circuits, quantify their impact on performance and review mitigation efforts. Finally, we discuss the constraints that arise from circuits having to operate within a living cell. Collectively, better tools, well-characterized parts and a comprehensive understanding of how to compose circuits are leading to a breakthrough in the ability to program living cells for advanced applications, from living therapeutics to the atomic manufacturing of functional materials.National Institute of General Medical Sciences (U.S.) (Grant P50 GM098792)National Institute of General Medical Sciences (U.S.) (Grant R01 GM095765)National Science Foundation (U.S.). Synthetic Biology Engineering Research Center (EEC0540879)Life Technologies, Inc. (A114510)National Science Foundation (U.S.). Graduate Research FellowshipUnited States. Office of Naval Research. Multidisciplinary University Research Initiative (Grant 4500000552

Probing the collective vibrational dynamics of a protein in liquid water by terahertz absorption spectroscopy

Biological polymers are expected to exhibit functionally relevant, global, and subglobal collective modes in the terahertz (THz) frequency range (i.e., picosecond timescale). In an effort to monitor these collective motions, we have experimentally determined the absorption spectrum of solvated bovine serum albumin (BSA) from 0.3 to 3.72 THz (10–124 cm−1). We successfully extract the terahertz molar absorption of the solvated BSA from the much stronger attenuation of water and observe in the solvated protein a dense, overlapping spectrum of vibrational modes that increases monotonically with increasing frequency. We see no evidence of distinct, strong, spectral features, suggesting that no specific collective vibrations dominate the protein's spectrum of motions, consistent with the predictions of molecular dynamics simulations and normal mode analyses of a range of small proteins. The shape of the observed spectrum resembles the ideal quadratic spectral density expected for a disordered ionic solid, indicating that the terahertz normal mode density of the solvated BSA may be modeled, to first order, as that of a three-dimensional elastic nanoparticle with an aperiodic charge distribution. Nevertheless, there are important detailed departures from that of a disordered inorganic solid or the normal mode densities predicted for several smaller proteins. These departures are presumably the spectral features arising from the unique molecular details of the solvated BSA. The techniques used here and measurements have the potential to experimentally confront theoretical calculations on a frequency scale that is important for macromolecular motions in a biologically relevant water environment

Immunotoxicology of beryllium lung disease

Beryllium induces non-caseating granulomatous inflammation in humans exposed to the metal dust or fumes in both occupational and non-occupational settings. The resulting condition, chronic beryllium disease (CBD), affects principally the lungs, lymphatics, and skin and continues to plague modern industry. Beryllium exerts several important immunotoxic effects, including induction of a beryllium-antigen specific adaptive immune response and the triggering of inflammatory and innate immune responses. Genetic susceptibility plays a role in CBD adaptive immune responses, mainly mediated through single nucleotide polymorphisms in HLA-DP and, to a lesser extent, HLA-DR. The adaptive response is characterized by influx and proliferation of CD4+ central and effector memory T cells expressing Th1 cytokines. Insights into the immunopathogenesis of CBD have implications for the understanding of other immune-mediated granulomatous disorders and for metal antigen behavior