NEUTRON ACTIVATION ANALYSIS: CLINICAL AND BIOLOGICAL STUDIES OF MANGANESE

From Symposium on Radioactivation Analysis and its Application to the Biological Sciences, Saclay, France, Sept. 1963. The use of neutron activation analysis for studying the metabolism of manganese in the body is discussed. Results of various clinical and biological studies of manganese metabolism are described. Some of the results indicate that pigments (melanin) in general contain high manganese concentrations and might play a role in extrapyramidal diseases. (D.L.C.

Molecular interactions of zinc with the glycine receptor.

The ionotropic receptors including nicotinic acetylcholine (nAChR), y-aminobutyric acid type A and C (GABAa/c), serotonin (5HT-3) and glycine receptors (GlyR) all comprise the cys-loop receptor family. A pentameric configuration is adopted by these receptors featuring a large extra cellular domain, four transmembrane (M) spanning domains and an intracellular compartment primarily contributed from the M3-4 loop. The recent advent of an X-ray crystal structure of the related ACh binding protein from snail, Lymnaea stagnalis, and an electron micrograph nearing atomic resolution of the transmembrane domains for the Torpedo nAChR provide the opportunity to homology model the structures of all cys-loop ligand-gated receptors and investigate critical elements of receptor function with unprecedented accuracy. By using homology modelling to guide site-directed mutagenesis in combination with whole-cell patch clamp electrophysiology, molecular elements that mediate the biphasic modulation of glycine receptors by Zn2+ were investigated. The structure of a previously identified low sensitivity inhibitory Zn2+ site was clarified revealing critical determinants of GlyR subtype selectivity for Zn2+ mediated inhibition. Intriguingly these experiments also revealed a novel functional asymmetry at this site suggesting that one specific side of the site directs downstream transduction of the inhibitory Zn2 effect. This enabled the elucidation of a hydrophobic pathway leading directly through the core of the GlyR from the inhibitory Zn2+ site to the agonist binding site suggesting a mechanism for Zn2+ mediated inhibition. This study also investigated the structural basis for Zn2* enhancement of GlyR function. A comparative study of GlyR al and a2 followed by a directed mutagenesis regional scan led to the identification of a complete and novel site for Zn2+ potentiation. Further studies also elucidated a potential mechanism of action for this site by identifying an important gating component of the GlyR, which exhibited a strong interaction with this novel potentiation site for Zn2+. These studies demonstrate the power of a homology modelling strategy to resolve key elements of cys-loop ligand-gated receptor function. Identifying and understanding receptor modulation by allosteric effectors is a key requisite to understanding receptor function. This work describes the key structural determinants involved in the biphasic Zn2+ modulation of GlyRs both in terms of actual binding sites and downstream effector mechanisms

Impacts of Mobility Management and Human Service Transportation Coordination Efforts and End-User Quality of Life

This study developed an evaluation method to examine the effectiveness of mobility management and coordination programs in a community. A series of surveys were conducted of both transit users and stakeholders in communities across the country. Results from these surveys suggest improvements have occurred in efficiencies, ease of access, and quality of service. Most respondents to the stakeholder survey reported benefits that have been realized. Results from an ordered probit model demonstrate the positive impacts that improved mobility has on life satisfaction

Dense non-aqueous phase liquids at former manufactured gas plants: Challenges to modeling and remediation

The remediation of dense non-aqueous phase liquids (DNAPLs) in porous media continues to be one of the most challenging problems facing environmental scientists and engineers. Of all the environmentally relevant DNAPLs, tars in the subsurface at former manufactured gas plants (FMGP’s) pose one of the biggest challenges due to their complex chemical composition and tendency to alter wettability. To further our understanding of these complex materials, we consulted historic documentation to evaluate the impact of gas manufacturing on the composition and physicochemical nature of the resulting tars. In the recent literature, most work to date has been focused in a relatively narrow portion of the expected range of tar materials, which has yielded a bias toward samples of relatively low viscosity and density. In this work, we consider the dissolution and movement of tars in the subsurface, models used to predict these phenomena, and approaches used for remediation. We also explore the open issues and detail important gaps in our fundamental understanding of these extraordinarily complex systems that must be resolved to reach a mature level of understanding

Design and Characterization of a Neutron Calibration Facility for the Study of sub-keV Nuclear Recoils

As part of an experimental effort to demonstrate sensitivity in a large-mass detector to the ultra-low energy recoils expected from coherent neutrino-nucleus elastic scattering, we have designed and built a highly monochromatic 24 keV neutron beam at the Kansas State University Triga Mark-II reactor. The beam characteristics were chosen so as to mimic the soft recoil energies expected from reactor antineutrinos in a variety of targets, allowing to understand the response of dedicated detector technologies in this yet unexplored sub-keV recoil range. A full characterization of the beam properties (intensity, monochromaticity, contaminations, beam profile) is presented, together with first tests of the calibration setup using proton recoils in organic scintillator.Comment: submitted to Nucl. Instr. Meth.

Amyloid precursor protein cleavage-dependent and -independent axonal degeneration programs share a common nicotinamide mononucleotide adenylyltransferase 1-sensitive pathway

Axonal degeneration is a hallmark of many debilitating neurological disorders and is thought to be regulated by mechanisms distinct from those governing cell body death. Recently, caspase 6 activation via APP cleavage and activation of DR6 was discovered to induce axon degeneration after NGF withdrawal. We tested whether this pathway is involved in axonal degeneration caused by withdrawal of other trophic support, axotomy or vincristine exposure. Neurturin deprivation, like NGF withdrawal activated this APP/DR6/caspase 6 pathway and resulted in axonal degeneration, however, APP cleavage and caspase 6 activation were not involved in axonal degeneration induced by mechanical or toxic insults. However, loss of surface APP (sAPP) and caspase 6 activation were observed during axonal degeneration induced by dynactin 1(Dctn1) dysfunction, which disrupts axonal transport. Mutations in Dctn1 are associated with motor neuron disease and frontal temporal dementia, thus suggesting that the APP/caspase 6 pathway could be important in specific types of disease-associated axonal degeneration. The NGF deprivation paradigm, with its defined molecular pathway, was used to examine the context of Nmnat-mediated axonal protection. We found that although Nmnat blocks axonal degeneration after trophic factor withdrawal, it did not prevent loss of axon sAPP or caspase 6 activation within the axon, suggesting it acts downstream of caspase 6. These results indicate that diverse insults induce axonal degeneration via multiple pathways and that these degeneration signals converge on a common, Nmnat-sensitive program that is uniquely involved in axonal, but not cell body, degeneration

Two-temperature relaxation and melting after absorption of femtosecond laser pulse

The theory and experiments concerned with the electron-ion thermal relaxation and melting of overheated crystal lattice constitute the subject of this paper. The physical model includes two-temperature equation of state, many-body interatomic potential, the electron-ion energy exchange, electron thermal conductivity, and optical properties of solid, liquid, and two phase solid-liquid mixture. Two-temperature hydrodynamics and molecular dynamics codes are used. An experimental setup with pump-probe technique is used to follow evolution of an irradiated target with a short time step 100 fs between the probe femtosecond laser pulses. Accuracy of measurements of reflection coefficient and phase of reflected probe light are ~1% and \sim 1\un{nm}, respectively. It is found that, {\it firstly}, the electron-electron collisions make a minor contribution to a light absorbtion in solid Al at moderate intensities; {\it secondly}, the phase shift of a reflected probe results from heating of ion subsystem and kinetics of melting of Al crystal during 0 where $t$ is time delay between the pump and probe pulses measured from the maximum of the pump; {\it thirdly} the optical response of Au to a pump shows a marked contrast to that of Al on account of excitation of \textit{d}-electronsComment: 6th International Conference on Photo-Excited Processes and Applications 9-12 Sep 2008, Sapporo, Japan, http://www.icpepa6.com, the contributed paper will be published in Applied Surface Science(2009

MobiQ: A modular Android application for collecting social interaction, repeated survey, GPS and photographic data

The MobiQ app for Android smartphones is a feature-rich application enabling a novel approach to data collection for longitudinal surveys. It combines continuous automatic background data collection with user supplied data. It can prompt users to complete questionnaires at regular intervals, and allows users to upload photographs for social research projects. The app has the capability to collect GPS location data, and calls and text frequency (excluding content) unobtrusively. The app transmits data to a secure cloud rather than storing research data on the phone, but can also store data temporarily if a data connection is unavailable; hence, MobiQ offers data security advantages over text- or web-based surveys using phones. MobiQ has been pilot tested in the field in a social science research project and is able to collect longitudinal social research data. Due to its modular and flexible design, MobiQ can easily be adapted to suit different research questions. Furthermore, its core design approach which allows for long-term power efficient data collection can be re-used outside the social sciences domain for other kinds of smartphone-based data-driven projects. Projects that have a requirement for communications-based, sensors-based, user-based data collection or any combination of these may find our code and design approach beneficial. For example, MobiQ code and architecture has been successfully adapted to build an app for a project investigating smartphone-based implicit authentication for mobile access control

Targeted delivery of antisense oligonucleotides by molecular conjugates

Antisense oligonucleotides efficiently inhibit gene expression in vitro; however, the successful therapeutic application of this technology in vivo will require the development of improved delivery systems. In this report we describe a technique that efficiently delivers antisense oligonucleotides into cells using molecular conjugates. This technique, which was initially developed for the delivery of eukaryotic genes, is based on the construction of DNA-protein complexes that are recognized by the liver-specific asialoglycoprotein receptor. Binding of poly( l -lysine)-asialoorosomucoid (AsOR) protein conjugates with phosphorothioate antisense oligonucleotides to chloramphenicol acetyltransferase (CAT) led to the formation of 50- to 150-nm toroids. Exposure of the antisense molecular complexes (3 µM oligonucleotide) to NIH 3T3 cells genetically modified to express both the AsOR receptor and CAT, inhibited CAT expression by 54%, which was completely blocked by excess AsOR. Equivalent inhibition of CAT activity with purified oligonucleotide alone was observed at a 30 µM concentration. Furthermore, examination of the cells using indirect immunofluorescence for the presence of CAT protein showed 28% of cells exposed to the molecular conjugates lacked any detectable CAT enzyme. Cells exposed to oligonucleotide alone showed a highly variable staining pattern, and only a few of the cells were completely void of CAT protein. Together these data demonstrate that molecular conjugates provide a highly specific and efficient system for the delivery of antisense oligonucleotides.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45543/1/11188_2005_Article_BF01232652.pd