The cardiovascular effects of air pollution: Prevention and reversal by pharmacological agents

Air pollution is associated with staggering levels of cardiovascular morbidity and mortality. Airborne particulate matter (PM), in particular, has been associated with a wide range of detrimental cardiovascular effects, including impaired vascular function, raised blood pressure, alterations in cardiac rhythm, blood clotting disorders, coronary artery disease, and stroke. Considerable headway has been made in elucidating the biological processes underlying these associations, revealing a labyrinth of multiple interacting mechanistic pathways. Several studies have used pharmacological agents to prevent or reverse the cardiovascular effects of PM; an approach that not only has the advantages of elucidating mechanisms, but also potentially revealing therapeutic agents that could benefit individuals that are especially susceptible to the effects of air pollution. This review gathers investigations with pharmacological agents, offering insight into the biology of how PM, and other air pollutants, may cause cardiovascular morbidity

SONTRAC—a scintillating plastic fiber tracking detector for neutron and proton imaging spectroscopy

SONTRAC (SOlar Neutron TRACking imager and spectrometer) is a conceptual instrument intended to measure the energy and incident direction of 20–150 MeV neutrons produced in solar flares. The intense neutron background in a low-Earth orbit requires that imaging techniques be employed to maximize an instrument’s signal-to-noise ratio. The instrument is comprised of mutually perpendicular, alternating layers of parallel, scintillating, plastic fibers that are viewed by optoelectronic devices. Two stereoscopic views of recoil proton tracks are necessary to determine the incident neutron’s direction and energy. The instrument can also be used as a powerful energetic proton imager. Data from a fully functional 3-d prototype are presented. Early results indicate that the instrument’s neutron energy resolution is approximately 10% with the neutron incident direction determined to within a few degrees

A replicated study on nuclear proliferation shows the critical necessity of reviewing accepted scientific results.

In replicating a 2009 study on the role of asymmetric nuclear weapons possession, Mark Bell and Nicholas Miller found that a computational error led to the overestimation of the deterrent effect of nuclear weapons by a factor of several million. It is only through constant re-evaluation of scholarly findings that scholars can reach sufficiently robust conclusions that merit the attention of policymakers

Single-sided CZT strip detectors

We report progress in the study of thick CZT strip detectors for 3-D imaging and spectroscopy and discuss two approaches to device design. Unlike double-sided strip detectors, these devices feature both row and column contacts implemented on the anode surface. This electron-only approach circumvents problems associated with poor hole transport in CZT that normally limit the thickness and energy range of double-sided strip detectors. The work includes laboratory and simulation studies aimed at developing compact, efficient, detector modules for 0.05 to 1 MeV gamma radiation measurements while minimizing the number and complexity of the electronic readout channels. These devices can achieve similar performance to pixel detectors for both 3-D imaging and spectroscopy. The low channel count approach can significantly reduce the complexity and power requirements of the readout electronics. This is particularly important in applications requiring large area detector arrays. We show two single-sided strip detector concepts. One, previously reported, features rows established with collecting contacts and columns with noncollecting contacts. Another, introduced here, operates on a charge sharing principle and establishes both rows and columns with collecting contacts on the anode surface. In previous work using the earlier strip detector concept we reported simulations and measurements of energy and spatial resolution for prototype 5- and 10-mm-thick CZT detectors. We now present the results of detection efficiency and uniformity measurements conducted on 5-mm-thick detectors using a specific configuration of the front-end electronics and event trigger. We discuss the importance of the detector fabrication processes when implementing this approach

Thermodynamics and the Global Optimization of Lennard-Jones clusters

Theoretical design of global optimization algorithms can profitably utilize recent statistical mechanical treatments of potential energy surfaces (PES's). Here we analyze the basin-hopping algorithm to explain its success in locating the global minima of Lennard-Jones (LJ) clusters, even those such as \LJ{38} for which the PES has a multiple-funnel topography, where trapping in local minima with different morphologies is expected. We find that a key factor in overcoming trapping is the transformation applied to the PES which broadens the thermodynamic transitions. The global minimum then has a significant probability of occupation at temperatures where the free energy barriers between funnels are surmountable.Comment: 13 pages, 13 figures, revte

The double-funnel energy landscape of the 38-atom Lennard-Jones cluster

The 38-atom Lennard-Jones cluster has a paradigmatic double-funnel energy landscape. One funnel ends in the global minimum, a face-centred-cubic (fcc) truncated octahedron. At the bottom of the other funnel is the second lowest energy minimum which is an incomplete Mackay icosahedron. We characterize the energy landscape in two ways. Firstly, from a large sample of minima and transition states we construct a disconnectivity tree showing which minima are connected below certain energy thresholds. Secondly we compute the free energy as a function of a bond-order parameter. The free energy profile has two minima, one which corresponds to the fcc funnel and the other which at low temperature corresponds to the icosahedral funnel and at higher temperatures to the liquid-like state. These two approaches show that the greater width of the icosahedral funnel, and the greater structural similarity between the icosahedral structures and those associated with the liquid-like state, are the cause of the smaller free energy barrier for entering the icosahedral funnel from the liquid-like state and therefore of the cluster's preferential entry into this funnel on relaxation down the energy landscape. Furthermore, the large free energy barrier between the fcc and icosahedral funnels, which is energetic in origin, causes the cluster to be trapped in one of the funnels at low temperature. These results explain in detail the link between the double-funnel energy landscape and the difficulty of global optimization for this cluster.Comment: 12 pages, 11 figures, revte

Monoclonal Antibody Identification of Subpopulations of Cerebral Cortical Neurons Affected in Alzheimer disease

Neuronal degeneration is one of the hallmarks of Alzheimer disease (AD). Given the paucity of molecular markers available for the identification of neuronal subtypes, the specificity of neuronal loss within the cerebral cortex has been difficult to evaluate. With a panel of four monoclonal antibodies (mAbs) applied to central nervous system tissues from AD patients, we have immunocytochemically identified a population of vulnerable cortical neurons; a subpopulation of pyramidal neurons is recognized by mAbs 3F12 and 44.1 in the hippocampus and neocortex, and clusters of multipolar neurons in the entorhinal cortex reactive with mAb 44.1 show selective degeneration. Closely adjacent stellate-like neurons in these regions, identified by mAb 6A2, show striking preservation in AD. The neurons recognized by mAbs 3F12 and 44.1, to the best of our knowledge, do not comprise a single known neurotransmitter system. mAb 3A4 identifies a phosphorylated antigen that is undetectable in normal brain but accumulates early in the course of AD in somas of vulnerable neurons. Antigen 3A4 is distinct from material reactive with thioflavin S or antibody generated against paired helical filaments. Initially, antigen 3A4 is localized to neurons in the entorhinal cortex and subiculum, later in the association neocortex, and, ultimately in cases of long duration, in primary sensory cortical regions. mAb 3F12 recognizes multiple bands on immunoblots of homogenates of normal and Ad cortical tissues, whereas mAb 3A4 does not bind to immunoblots containing neurofilament proteins or brain homogenates from AD patients. Ultrastructurally, antigen 3A4 is localized to paired-helical filaments. Using these mAbs, further molecular characterization of the affected cortical neurons is now possible

Readout and performance of thick CZT strip detectors with orthogonal coplanar anodes

We report progress in the study of CZT strip detectors featuring orthogonal coplanar anode contacts. The work includes laboratory and simulation studies aimed at optimizing and developing compact, efficient, high performance detector modules for 0.05 to 1 MeV gamma radiation measurements. The novel coplanar anode strip configuration retains many of the performance advantages of pixel detectors yet requires far fewer electronic channels to perform both 3-d imaging and spectroscopy. We report on studies aimed at determining an optimum configuration of the analog signal processing electronics to employ with these detectors. We report measurements of energy and spatial resolution in three dimensions for prototype 5 and 10 mm thick CZT detectors using a set of shaping and summing amplifiers