The small quinolone derived compound HT61 enhances the effect of tobramycin against Pseudomonas aeruginosa in vitro and in vivo.

HT61 is a small quinolone-derived compound previously demonstrated to exhibit bactericidal activity against gram-positive bacteria including methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). When combined with the classical antibiotics and antiseptics neomycin, gentamicin, mupirocin and chlorhexidine, HT61 demonstrated synergistic bactericidal activity against both MSSA and MRSA infections in vitro. In this study, we investigated the individual antimicrobial activity of HT61 alongside its capability to increase the efficacy of tobramycin against both a tobramycin sensitive laboratory reference strain (PAO1) and tobramycin resistant clinical isolates (RP73, NN2) of the gram-negative bacteria Pseudomonas aeruginosa (P. aeruginosa). Using broth microdilution methods, the MICs of HT61 against all strains were assessed, as well as the effect of HT61 in combination with tobramycin using both the chequerboard method and bacterial time-kill assays. A murine model of pulmonary infection was also used to evaluate the combination therapy of tobramycin and HT61 in vivo. In these studies, we demonstrated significant synergism between HT61 and Tobramycin against the tobramycin resistant P. aeruginosa strains RP73 and NN2, whilst an additive/intermediate effect was observed for P. aeruginosa strain PA01 which was further confirmed using bacterial time kill analysis. In addition, the enhancement of tobramycin by HT61 was also evident in in vitro assays of biofilm eradication. Finally, in vivo studies revealed analogous effects to those observed in vitro with HT61 when administered in combination with tobramycin against each of the three P. aeruginosa strains at the highest tested dose (10 mg/kg)

Comparative population structure of <i>Plasmodium malariae</i> and <i>Plasmodium falciparum</i> under different transmission settings in Malawi

&lt;b&gt;Background:&lt;/b&gt; Described here is the first population genetic study of Plasmodium malariae, the causative agent of quartan malaria. Although not as deadly as Plasmodium falciparum, P. malariae is more common than previously thought, and is frequently in sympatry and co-infection with P. falciparum, making its study increasingly important. This study compares the population parameters of the two species in two districts of Malawi with different malaria transmission patterns - one seasonal, one perennial - to explore the effects of transmission on population structures. &lt;BR/&gt; &lt;b&gt;Methods:&lt;/b&gt; Six species-specific microsatellite markers were used to analyse 257 P. malariae samples and 257 P. falciparum samples matched for age, gender and village of residence. Allele sizes were scored to within 2 bp for each locus and haplotypes were constructed from dominant alleles in multiple infections. Analysis of multiplicity of infection (MOI), population differentiation, clustering of haplotypes and linkage disequilibrium was performed for both species. Regression analyses were used to determine association of MOI measurements with clinical malaria parameters. &lt;BR/&gt; &lt;b&gt;Results:&lt;/b&gt; Multiple-genotype infections within each species were common in both districts, accounting for 86.0% of P. falciparum and 73.2% of P. malariae infections and did not differ significantly with transmission setting. Mean MOI of P. falciparum was increased under perennial transmission compared with seasonal (3.14 vs 2.59, p = 0.008) and was greater in children compared with adults. In contrast, P. malariae mean MOI was similar between transmission settings (2.12 vs 2.11) and there was no difference between children and adults. Population differentiation showed no significant differences between villages or districts for either species. There was no evidence of geographical clustering of haplotypes. Linkage disequilibrium amongst loci was found only for P. falciparum samples from the seasonal transmission setting. &lt;BR/&gt; &lt;b&gt;Conclusions:&lt;/b&gt; The extent of similarity between P. falciparum and P. malariae population structure described by the high level of multiple infection, the lack of significant population differentiation or haplotype clustering and lack of linkage disequilibrium is surprising given the differences in the biological features of these species that suggest a reduced potential for out-crossing and transmission in P. malariae. The absence of a rise in P. malariae MOI with increased transmission or a reduction in MOI with age could be explained by differences in the duration of infection or degree of immunity compared to P. falciparum

Eighteenth Year of the Gulf of Maine Environmental Monitoring Program

This report summarizes the metals and organic contaminant data associated with the collection and analyses of blue mussel (Mytilus edulis) tissue from selected sites along the Gulf of Maine coast during the 2008 sampling season. Contaminant monitoring is conducted by the Gulfwatch Program for the Gulf of Maine Council on the Marine Environment (GOMC). A subset of these data is compared with analytical results from earlier Gulfwatch monitoring (2001-2007). Statistical analyses are limited to descriptive measures of replicates from selected sampling sites and include: arithmetic means, and appropriate measures of variance. The primary purpose of this report is to present the current annual results, present graphical representation of spatial and temporal trends and identify potential outliers in order to provide investigators and other interested persons with contemporary information concerning water quality in the Gulf of Maine, as reflected by uptake into resident shellfish (mussels and clams)

Differential in-gel electrophoresis (DIGE): The key to finding the 4936 factor? [abstract]

Abstract only availableThere are many species of plants that do not accept their own or closely related pollen. This self-incompatibility (SI), is seen in members of the genus Nicotiana. There are three proteins that are known to be required for SI to function in the pistil: S-RNase, 120K and HT-B. We discovered a mutation segregating in a population of otherwise SI plants that prevents SI from functioning in the pistil. Plants that display normal SI are called Rejectors (because they reject their own pollen), and mutants are called Acceptors (because they accept their own pollen). Acceptors show normal expression of S-RNase, 120K, and HT-B. The factor responsible for the mutation was named the 4936 Factor after the population in which it was first discovered. In order to Identify the 4936 Factor, I have used the DIGE method. Total protein extracts from Acceptor and Rejector pistils are stained with two different fluorophores and run in the same two-dimensional gel. By separating proteins both by size and isoelectric point, one can search for differences in the expression level or presence/absence of a particular protein. Therefore, a protein that is present in the rejector color, but not in the acceptor color, is a good candidate for further investigation as the 4936 Factor.MU Monsanto Undergraduate Research Fellowshi

Developing Flexible, Networked Lighting Control Systems That Reliably Save Energy in California Buildings

An important strategy to meet California's ambitious energy efficiency goals is to use innovative wireless communications, embedded sensors, data analytics and controls to significantly reduce lighting energy use in commercial buildings. This project developed a suite of networked lighting solutions to further this goal. The technologies include a platform for low-cost sensing, distributed intelligence and communications, the “PermaMote,” which is a self-powered sensor and controller for lighting applications. The project team also developed a task ambient daylighting system that integrates sensors with data-driven daylighting control using an open communication interface, called the “Readings-At-Desk” (RAD) system. To address the problem of building occupants being confused about how to operate traditional lighting control systems, the research team created content that could be the basis for a user interface standard for lighting controls. Finally, to address the difficulty of ensuring that advanced lighting control systems actually deliver their promised energy savings, the project team developed a new method for evaluating and specifying lighting systems’ performance. The research team validated these technologies in the laboratory, showing significant lighting energy savings, up to 73% for the PermaMote sensor system from occupancy control and daylight dimming features, compared to the same light source (LED replacement lamps) operated via simple on/off scheduling. The project team also developed a proposed standard lighting data model and user interface elements, which were contributed to the ANSI Lighting Systems Committee (C137) for standardization. Existing data models are incomplete and inconsistent, whereas the lighting-specific data model developed here is clear and comprehensive, to serve as a starting point for creating common, universally agreed upon semantic definitions of key lighting parameters, to promote interoperability. For the task on verifiable performance of lighting systems, the project team developed a more effective metric for capturing the actual energy impact of a lighting system over time — the energy usage intensity (kWh/ft2/year). Three commercial lighting systems were tested in FLEXLAB® using this new metric, and the tests show a wide range in the accuracy of the self-reported energy-use metric, from 0.5% to 28% error compared to direct measurement of lighting energy using dedicated submeters. Overall, the project team estimates that these advanced technologies can reduce California office lighting energy use by 20% (above and beyond normal advanced lighting controls mandated by Title 24), resulting in about 1,600 GWh/year in savings

Constraining Spinning Dust Parameters with the WMAP Five-Year Data

We characterize spinning dust emission in the warm ionized medium by comparing templates of Galactic dust and Halpha with the 5-year maps from the Wilkinson Microwave Anisotropy Probe. The Halpha-correlated microwave emission deviates from the thermal bremsstrahlung (free-free) spectrum expected for ionized gas, exhibiting an additional broad bump peaked at ~40 GHz which provides ~20% of the peak intensity. We confirm that the bump is consistent with a modified Draine & Lazarian (1998) spinning dust model, though the peak frequency of the emission is somewhat lower than the 50 GHz previously claimed. This frequency shift results from systematic errors in the large-scale modes of the 3-year WMAP data which have been corrected in the 5-year data release. We show that the bump is not the result of errors in the Halpha template by analyzing regions of high free-free intensity, where the WMAP K-band map may be used as the free-free template. We rule out a pure free-free spectrum for the Halpha-correlated emission at high confidence: ~27sigma for the nearly full-sky fit, even after marginalizing over the CMB cross-correlation bias. We also extend the previous analysis by searching the parameter space of the Draine & Lazarian model but letting the amplitude float. The best fit for reasonable values of the characteristic electric dipole moment and density requires an amplitude factor of ~0.3. This suggests that small PAHs in the warm ionized medium are depleted by a factor of ~3.Comment: 17 pages, 13 figures; submitted to Ap

Purism, Variation, Change and ‘Authenticity’: Ideological Challenges to Language Revitalisation

This paper is based on recent research into the small, highly endangered language Giernesiei 1 (Guernsey, Channel Islands). 2 Language documentation has found unexpectedly rich variation and change in Giernesiei usage, not all of which can be accounted for by regional and age-related factors. At the same time, our research into language ideologies and efforts to maintain and revitalise Giernesiei has revealed deep-seated purist or ‘traditionalist’ language attitudes that resist and deny language change. This nostalgic view of language and culture can hyper-valorise ‘authentic’ traditions (arguably reinvented 3 ) and can lead to reluctance to share Giernesiei effectively with younger generations who might ‘change the language’, despite an overt desire to maintain it. This mismatch between ideologies and practices can be seen at language festivals, in lessons for children, and in the experiences of adult learners who were interviewed as part of a British Academy-funded project. I present a taxonomy of reactions to variation in Giernesiei, which confirms and extends the findings of Jaffe 4 in Corsica. I also discuss recent revitalisation efforts that try to bring together older and ‘new’ speakers and promote the role of adult learners and ‘re-activate’ semi-speakers. The findings support the view that full evaluation of language vitality should include documenting the processes and ideologies of language revitalisation. 5 ,

Precision Epoch of Reionization studies with next-generation CMB experiments

Future arcminute resolution polarization data from ground-based Cosmic Microwave Background (CMB) observations can be used to estimate the contribution to the temperature power spectrum from the primary anisotropies and to uncover the signature of reionization near $\ell=1500$ in the small angular-scale temperature measurements. Our projections are based on combining expected small-scale E-mode polarization measurements from Advanced ACTPol in the range $300<\ell<3000$ with simulated temperature data from the full Planck mission in the low and intermediate $\ell$ region, $2<\ell<2000$. We show that the six basic cosmological parameters determined from this combination of data will predict the underlying primordial temperature spectrum at high multipoles to better than $1\%$ accuracy. Assuming an efficient cleaning from multi-frequency channels of most foregrounds in the temperature data, we investigate the sensitivity to the only residual secondary component, the kinematic Sunyaev-Zel'dovich (kSZ) term. The CMB polarization is used to break degeneracies between primordial and secondary terms present in temperature and, in effect, to remove from the temperature data all but the residual kSZ term. We estimate a $15 \sigma$ detection of the diffuse homogeneous kSZ signal from expected AdvACT temperature data at $\ell>1500$, leading to a measurement of the amplitude of matter density fluctuations, $\sigma_8$, at $1\%$ precision. Alternatively, by exploring the reionization signal encoded in the patchy kSZ measurements, we bound the time and duration of the reionization with $\sigma(z_{\rm re})=1.1$ and $\sigma(\Delta z_{\rm re})=0.2$. We find that these constraints degrade rapidly with large beam sizes, which highlights the importance of arcminute-scale resolution for future CMB surveys.Comment: 10 pages, 10 figure