Synthesis, in vitro evaluation, and radiolabeling of fluorinated puromycin analogues: potential candidates for PET imaging of protein synthesis

There is currently no ideal radiotracer for imaging protein synthesis rate (PSR) by positron emission tomography (PET). Existing fluorine-18 labelled amino acid-based radiotracers predominantly visualize amino acid transporter processes, and in many cases they are not incorporated into nascent proteins at all. Others are radiolabelled with the short half-life positron emitter carbon-11 which is rather impractical for many PET centers. Based on the puromycin (6) structural manifold, a series of 10 novel derivatives of 6 was prepared via Williamson ether synthesis from a common intermediate. A bioluminescence assay was employed to study their inhibitory action on protein synthesis which identified fluoroethyl analogue (7b) as a lead compound. The fluorine-18 analogue was prepared via nucleophilic substitution of the corresponding tosylate precursor in modest radiochemical yield 2±0.6% and excellent radiochemical purity (>99%) and showed complete stability over 3 h at ambient temperature

The feasibility and effectiveness of a web-based personalised feedback and social norms alcohol intervention in UK university students: A randomised control trial

OBJECTIVE Alcohol misuse amongst University students is a serious concern, and research has started to investigate the feasibility of using e-health interventions. This study aimed to establish the effectiveness of an electronic web-based personalised feedback intervention through the use of a randomised control trial (RCT). METHODS 506 participants were stratified by gender, age group, year of study, self-reported weekly consumption of alcohol and randomly assigned to either a control or intervention condition. Intervention participants received electronic personalised feedback and social norms information on their drinking behaviour which they could access by logging onto the website at any time during the 12-week period. CAGE score, average number of alcoholic drinks consumed per drinking occasion, and alcohol consumption over the last week were collected from participants at pre- and post-survey. RESULTS A significant difference in pre- to post-survey mean difference of alcohol consumed per occasion was found, with those in the intervention condition displaying a larger mean decrease when compared to controls. No intervention effect was found for units of alcohol consumed per week or for CAGE scores. Sixty-three percent of intervention participants agreed that the feedback provided was useful. Those intervention participants who were above the CAGE cut off were more likely to report that the website would make them think more about the amount they drank. CONCLUSIONS Delivering an electronic personalised feedback intervention to students via the World Wide Web is a feasible and potentially effective method of reducing student alcohol intake. Further research is needed to replicate this outcome, evaluate maintenance of any changes, and investigate the process of interaction with web-based interventions

A SANS and APT study of precipitate evolution and strengthening in a maraging steel

In this work a combination of the characterisation techniques small angle neutron scattering (SANS) and atom probe tomography (APT) are used to study the precipitation in a maraging steel. Three similar maraging steel alloys were aged at different temperatures and ageing times, and then characterised using SANS, APT and microhardness. The alloys consist of two types of precipitates, namely Laves phase and β-NiAl, the precipitates have different composition and hence precipitate ageing, which makes it complicated to model. The SANS experimental set-up was relatively simple and allowed the precipitate size and fraction of a large number of samples to be measured in a single experiment. The APT results were used for constraining the SANS modelling, particularly the composition, shape and distribution of phases. The characterisation led to the following description of precipitation: NiAl phase reaches coarsening at early stages of ageing and shifts its strength mechanisms from shearing to Orowan looping, which cause the characteristic peak strength; the Laves phase is in growth throughout and its strength contribution increases with ageing time. These observations were shown to be consistent with precipitate evolution and strengthening models, and the work of others. Although, there are some issues with the combination of SANS and APT approach, which are discussed, the methodology provides a valuable tool to understand complex precipitation behaviours

Ice Nucleating Particle Connections to Regional Argentinian Land Surface Emissions and Weather During the Cloud, Aerosol, and Complex Terrain Interactions Experiment

Here, we present a multi-season study of ice-nucleating particles (INPs) active via the immersion freezing mechanism, which took place in north-central Argentina, a worldwide hotspot for mesoscale convective storms. INPs were measured untreated, after heating to 95°C, and after hydrogen peroxide digestion. No seasonal cycle of INP concentrations was observed. Heat labile INPs, which we define as “biological” herein, dominated the population active at −5 to −20°C, while non-heat-labile organic INPs (decomposed by peroxide) dominated at lower temperatures, from −20 to −28°C. Inorganic INPs (remaining after peroxide digestion), were minor contributors to the overall INP activity. Biological INP concentration active around −12°C peaked during rain events and under high relative humidity, reflecting emission mechanisms independent of the background aerosol concentration. The ratio of non-heat-labile organic and inorganic INPs was generally constant, suggesting they originated from the same source, presumably from regional arable topsoil based on air mass histories. Single particle mass spectrometry showed that soil particles aerosolized from a regionally common agricultural topsoil contained known mineral INP sources (K-feldspar and illite) as well as a significant organic component. The INP activity observed in this study correlates well with agricultural soil INP activities from this and other regions of the world, suggesting that the observed INP spectra might be typical of many arable landscapes. These results demonstrate the strong influence of regional continental landscapes, emitting INPs of types that are not yet well represented in global models

Infrared optical properties of Pr2CuO4

The ab-plane reflectance of a Pr2CuO4 single crystal has been measured over a wide frequency range at a variety of temperatures, and the optical properties determined from a Kramers-Kronig analysis. Above ~ 250 K, the low frequency conductivity increases quickly with temperature; the resistivity follows the form e^(E_a/k_BT), where E_a ~ 0.17 eV is much less than the inferred optical gap of ~ 1.2 eV. Transport measurements show that at low temperature the resistivity deviates from activated behavior and follows the form e^[(T_0/T)^1/4], indicating that the dc transport in this material is due to variable-range hopping between localized states in the gap. The four infrared-active Eu modes dominate the infrared optical properties. Below ~ 200 K, a striking new feature appears near the low-frequency Eu mode, and there is additional new fine structure at high frequency. A normal coordinate analysis has been performed and the detailed nature of the zone-center vibrations determined. Only the low-frequency Eu mode has a significant Pr-Cu interaction. Several possible mechanisms related to the antiferromagnetism in this material are proposed to explain the sudden appearance of this and other new spectral features at low temperature.Comment: 11 pages, 7 embedded EPS figures, REVTeX

Sheep Updates 2006 - part 3

This session covers six papers from different authors: GRAZING 1. Making better use of clover, Karen Venning and Andrew Thompson, Department of Primary Industries, Victoria 2. Grazing systems demonstration to optimise pasture utilisation and stocking rate, Mike Hyder, Sue-Ellen Shaw, Kelly Hill and Ron McTaggart, Department of Agriculture and Food Western Australia. 3. Know your audience to increase their rate of practice change - Lifetime Wool as an example, Gus Rose, Department of Agriculture and Food Western Australia, Carolyn Kabore, Kazresearch REPRODUCTION 4. Lifetime Wool - Ewe Management Guidlines, Mandy Curnow, Department of Agriculture and Food Western Australia 5. Achieving the best reproductive performance from your hoggets, Kenyon PR, Morris ST, West DM, Perkins NR, Pinchbeck GL., Institute of Veterinary, Animal and Biomedical Sciences, Massey University, New Zealand. 6. Lifetime Wool: Twin futures, Dr Ralph Behrendt, Department of Primary Industries, Victori

Low-temperature ice nucleation of sea spray and secondary marine aerosols under cirrus cloud conditions

Sea spray aerosols (SSAs) represent one of the most abundant aerosol types on a global scale and have been observed at all altitudes including the upper troposphere. SSA has been explored in recent years as a source of ice-nucleating particles (INPs) in cirrus clouds due to the ubiquity of cirrus clouds and the uncertainties in their radiative forcing. This study expands upon previous works on low-temperature ice nucleation of SSA by investigating the effects of atmospheric aging of SSA and the ice-nucleating activity of newly formed secondary marine aerosols (SMAs) using an oxidation flow reactor. Polydisperse aerosol distributions were generated from a marine aerosol reference tank (MART) filled with 120 L of real or artificial seawater and were dried to very low relative humidity to crystallize the salt constituents of SSA prior to their subsequent freezing, which was measured using a continuous flow diffusion chamber (CFDC). Results show that for primary SSA (pSSA), as well as aged SSA and SMA (aSSA+SMA) at temperatures &gt;220 K, homogeneous conditions (92 %–97 % relative humidity with respect to water – RHw) were required to freeze 1 % of the particles. However, below 220 K, heterogeneous nucleation occurs for both pSSA and aSSA+SMA at much lower RHw, where up to 1 % of the aerosol population freezes between 75 % and 80 % RHw. Similarities between freezing behaviors of the pSSA and aSSA+SMA at all temperatures suggest that the contributions of condensed organics onto the pSSA or alteration of functional groups in pSSA via atmospheric aging did not hinder the major heterogeneous ice nucleation process at these cirrus temperatures, which have previously been shown to be dominated by the crystalline salts. Occurrence of a 1 % frozen fraction of SMA, generated in the absence of primary SSA, was observed at or near water saturation below 220 K, suggesting it is not an effective INP at cirrus temperatures, similar to findings in the literature on other organic aerosols. Thus, any SMA coatings on the pSSA would only decrease the ice nucleation behavior of pSSA if the organic components were able to significantly delay water uptake of the inorganic salts, and apparently this was not the case. Results from this study demonstrate the ability of lofted primary sea spray particles to remain an effective ice nucleator at cirrus temperatures, even after atmospheric aging has occurred over a period of days in the marine boundary layer prior to lofting. We were not able to address aging processes under upper-tropospheric conditions.</p

Changes in microphytobenthos fluorescence over a tidal cycle: implications for sampling designs

Intertidal microphytobenthos (MPB) are important primary producers and provide food for herbivores in soft sediments and on rocky shores. Methods of measuring MPB biomass that do not depend on the time of collection relative to the time of day or tidal conditions are important in any studies that need to compare temporal or spatial variation, effects of abiotic factors or activity of grazers. Pulse amplitude modulated (PAM) fluorometry is often used to estimate biomass of MPB because it is a rapid, non-destructive method, but it is not known how measures of fluorescence are altered by changing conditions during a period of low tide. We investigated this experimentally using in situ changes in minimal fluorescence (F) on a rocky shore and on an estuarine mudflat around Sydney (Australia), during low tides. On rocky shores, the time when samples are taken during low tide had little direct influence on measures of fluorescence as long as the substratum is dry. Wetness from wave-splash, seepage from rock pools, run-off, rainfall, etc., had large consequences for any comparisons. On soft sediments, fluorescence was decreased if the sediment dried out, as happens during low-spring tides on particularly hot and dry days. Surface water affected the response of PAM and therefore measurements used to estimate MPB, emphasising the need for care to ensure that representative sampling is done during low tide

Search for extended gamma-ray emission from the Virgo galaxy cluster with Fermi-LAT

Galaxy clusters are one of the prime sites to search for dark matter (DM) annihilation signals. Depending on the substructure of the DM halo of a galaxy cluster and the cross sections for DM annihilation channels, these signals might be detectable by the latest generation of $\gamma$-ray telescopes. Here we use three years of Fermi Large Area Telescope (LAT) data, which are the most suitable for searching for very extended emission in the vicinity of nearby Virgo galaxy cluster. Our analysis reveals statistically significant extended emission which can be well characterized by a uniformly emitting disk profile with a radius of 3\deg that moreover is offset from the cluster center. We demonstrate that the significance of this extended emission strongly depends on the adopted interstellar emission model (IEM) and is most likely an artifact of our incomplete description of the IEM in this region. We also search for and find new point source candidates in the region. We then derive conservative upper limits on the velocity-averaged DM pair annihilation cross section from Virgo. We take into account the potential $\gamma$-ray flux enhancement due to DM sub-halos and its complex morphology as a merging cluster. For DM annihilating into $b\overline{b}$, assuming a conservative sub-halo model setup, we find limits that are between 1 and 1.5 orders of magnitude above the expectation from the thermal cross section for $m_{\mathrm{DM}}\lesssim100\,\mathrm{GeV}$. In a more optimistic scenario, we exclude $\langle \sigma v \rangle\sim3\times10^{-26}\,\mathrm{cm^{3}\,s^{-1}}$ for $m_{\mathrm{DM}}\lesssim40\,\mathrm{GeV}$ for the same channel. Finally, we derive upper limits on the $\gamma$-ray-flux produced by hadronic cosmic-ray interactions in the inter cluster medium. We find that the volume-averaged cosmic-ray-to-thermal pressure ratio is less than $\sim6\%$.Comment: 15 pages, 11 figures, 4 tables, accepted for publication in ApJ; corresponding authors: T. Jogler, S. Zimmer & A. Pinzk

Efficiency of the CATIE and BACS neuropsychological batteries in assessing cognitive effects of antipsychotic treatments in schizophrenia

Efficient and reliable assessments of cognitive treatment effects are essential for the comparative evaluation of procognitive effects of pharmacologic therapies. Yet, no studies have addressed the sensitivity and efficiency with which neurocognitive batteries evaluate cognitive abilities before and after treatment. Participants were primarily first episode schizophrenia patients who completed baseline (n = 367) and 12-week (n = 219) assessments with the BACS (Brief Assessment of Cognition in Schizophrenia) and CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) neuropsychological batteries in a clinical trial comparing olanzapine, quetiapine, and risperidone. Exploratory factor analysis revealed that performance on both batteries was characterized by a single factor of generalized cognitive deficit for both baseline performance and cognitive change after treatment. Both batteries estimated similar levels of change following treatment, although the BACS battery required half the administration time. Because a unitary factor characterized baseline cognitive abilities in early psychosis as well as cognitive change after treatment with atypical antipsychotic medications, short batteries such as the BACS may efficiently provide sufficient assessment of procognitive treatment effects with antipsychotic medications. Assessment of cognitive effects of adjunctive therapies targeting specific cognitive domains or impairments may require more extensive testing of the domains targeted to maximize sensitivity for detecting specific predicted cognitive outcomes