Synthesis and properties of charge transfer salts of BEDT-TTF

This research project has investigated the interplay of superconductivity and magnetism in organic systems, with the ultimate aim of observing their co-existence. In order to pursue this study, a series of charge transfer salts of BEDT-TTF (BEDT- TTF = bis ethylenedithio tetrathiafulvalene) have been successfully prepared with M(C2O4)33- anions (M = Fe, Cr and Co). The anion has been varied to systematically monitor the effect of localised moments on the conducting properties. Crystals with the general formula (BEDT -TTF)4AFe(C2O4)3.C6H5CN (A = K, NH4 or H2O) have been electrocrystallised and identified by X - ray crystallography. In the salts where A = K or NH4 a novel packing arrangement of the BEDT-TTF moiety is observed which involves the formation of monopositive BEDT-TTF units dimerising. These dimers are surrounded by six neutral BEDT-TTF molecules. Both of these materials are semiconductors with an activation energy of 0.14eV. Susceptibility measurements indicate that the dimers are spin paired and therefore the magnetic properties are dominated by the high spin Fe3+ complex. These results are reported in Chapter 3. The A = H2O salt is reported in Chapter 4. It is the first molecular superconductor containing localised magnetic moments, which has a transition temperature of 8.5K to the superconducting state. The BEDT-TTF molecules pack in the [beta]" fashion, which facilitates considerable overlap of the Sulfur orbitals. Susceptibility measurements at low field verify the superconducting transition, but as the field is increased, the paramagnetic signal from the Fe3+ becomes more dominant. At fields greater than 1 Tesla, the superconductivity is destroyed and the material obeys the Curie - Weiss law to 2K. A contribution from the conduction electrons is also observed. Band structure calculations suggest two dimensional metallic behaviour. Chapter 5 collates other compounds which have been prepared from solutions of BEDT-TTF and M(C2O4)33- (M = Fe, Cr, Co) in Benzonitrile. This has resulted in several new phases being isolated but due to multiple twinning, their structures have not yet been determined. Crystals grown from the solution where M = Cr are semimetallic to ∼ 150K at which temperature it undergoes a transition to the insulating state. The solvent has also been modified to include 5% Methanol. This has resulted in a superconducting phase whose lattice parameters have been determined. Efforts are currently being made to determine the full crystal structure. SQUID measurements indicate a Tc of 7.5K

Field-Evolved Resistance: Assessing the Problem and Ways to Move Forward

"Field-evolved resistance” is defined as a "genetically based decrease in susceptibility of a population to a toxin caused by exposure to the toxin in the field.” The key component of "field-evolved” resistance is that it does confer decreased susceptibility to an insecticide in the field. Another key component is that the decrease in susceptibility to the insecticide is because of previous exposure of the target insect to the toxin in the field. Several studies have reported field-evolved resistance to crops engineered to express proteins from the bacterium, Bacillus thuringiensis (Bt). However, there has not been a consistent standard in the application of the definition of field-evolved resistance for Bt crops. The inconsistency in applying the definition arises from differences in the methods used to detect resistance, the ecology of the interaction between the pest and the Bt crop, and the effective dose the pest encounters while feeding on the Bt crop. Using case studies of reported resistance to Bt crops, it is demonstrated resistance does not come in a single form, and that in most cases, resistance can still be manage

Growth of Mycobacterium tuberculosis biofilms containing free mycolic acids and harbouring drug-tolerant bacteria

Successful treatment of human tuberculosis requires 6–9 months' therapy with multiple antibiotics. Incomplete clearance of tubercle bacilli frequently results in disease relapse, presumably as a result of reactivation of persistent drug-tolerant Mycobacterium tuberculosis cells, although the nature and location of these persisters are not known. In other pathogens, antibiotic tolerance is often associated with the formation of biofilms – organized communities of surface-attached cells – but physiologically and genetically defined M. tuberculosis biofilms have not been described. Here, we show that M. tuberculosis forms biofilms with specific environmental and genetic requirements distinct from those for planktonic growth, which contain an extracellular matrix rich in free mycolic acids, and harbour an important drug-tolerant population that persist despite exposure to high levels of antibiotics

Facing the River Gauntlet: Understanding the Effects of Fisheries Capture and Water Temperature on the Physiology of Coho Salmon

An improved understanding of bycatch mortality can be achieved by complementing field studies with laboratory experiments that use physiological assessments. This study examined the effects of water temperature and the duration of net entanglement on physiological disturbance and recovery in coho salmon (Oncorhynchus kisutch) after release from a simulated beach seine capture. Heart rate was monitored using implanted electrocardiogram biologgers that allowed fish to swim freely before and after release. A subset of fish was recovered in respirometers to monitor metabolic recovery, and separate groups of fish were sacrificed at different times to assess blood and white muscle biochemistry. One hour after release, fish had elevated lactate in muscle and blood plasma, depleted tissue energy stores, and altered osmoregulatory status, particularly in warmer (15 vs. 10°C) and longer (15 vs. 2 min) capture treatments. A significant effect of entanglement duration on blood and muscle metabolites remained after 4 h. Oxygen consumption rate recovered to baseline within 7–10 h. However, recovery of heart rate to routine levels was longer and more variable, with most fish taking over 10 h, and 33% of fish failing to recover within 24 h. There were no significant treatment effects on either oxygen consumption or heart rate recovery. Our results indicate that fishers should minimize handling time for bycatch and maximize oxygen supply during crowding, especially when temperatures are elevated. Physiological data, such as those presented here, can be used to understand mechanisms that underlie bycatch impairment and mortality, and thus inform best practices that ensure the welfare and conservation of affected species

Fiber-Based Laser Transmitter Technology Maturation for Spectroscopic Measurements from Space

NASA's Goddard Space Flight Center has been developing lidar to remotely measure CO2 in the Earth's atmosphere. We have advanced the tunable laser technology to enable high-fidelity measurements from space. In this paper, we will report on the progress of fiber-based, 1.57-micron wavelength, laser transmitter that has demonstrated the optical performance required for a low earth orbiting instrument. The laser transmitter has been packaged and is undergoing environmental testing to demonstrate its technology readiness for space

The development and validation of the Virtual Tissue Matrix, a software application that facilitates the review of tissue microarrays on line

BACKGROUND: The Tissue Microarray (TMA) facilitates high-throughput analysis of hundreds of tissue specimens simultaneously. However, bottlenecks in the storage and manipulation of the data generated from TMA reviews have become apparent. A number of software applications have been developed to assist in image and data management; however no solution currently facilitates the easy online review, scoring and subsequent storage of images and data associated with TMA experimentation. RESULTS: This paper describes the design, development and validation of the Virtual Tissue Matrix (VTM). Through an intuitive HTML driven user interface, the VTM provides digital/virtual slide based images of each TMA core and a means to record observations on each TMA spot. Data generated from a TMA review is stored in an associated relational database, which facilitates the use of flexible scoring forms. The system allows multiple users to record their interpretation of each TMA spot for any parameters assessed. Images generated for the VTM were captured using a standard background lighting intensity and corrective algorithms were applied to each image to eliminate any background lighting hue inconsistencies or vignetting. Validation of the VTM involved examination of inter-and intra-observer variability between microscope and digital TMA reviews. Six bladder TMAs were immunohistochemically stained for E-Cadherin, β-Catenin and PhosphoMet and were assessed by two reviewers for the amount of core and tumour present, the amount and intensity of membrane, cytoplasmic and nuclear staining. CONCLUSION: Results show that digital VTM images are representative of the original tissue viewed with a microscope. There were equivalent levels of inter-and intra-observer agreement for five out of the eight parameters assessed. Results also suggest that digital reviews may correct potential problems experienced when reviewing TMAs using a microscope, for example, removal of background lighting variance and tint, and potential disorientation of the reviewer, which may have resulted in the discrepancies evident in the remaining three parameters

Fiber-Based Laser Transmitter at 1.57 Micrometers for Remote Sensing of Atmospheric Carbon Dioxide from Satellites

Over the past 20 years, NASA Goddard has successfully developed space-based lidar for remote sensing studies of the Earth and planets. The lidar in all missions to date have used diode pumped Nd:YAG laser transmitters. Recently we have been concentrating work on developing integrated path differential absorption (IPDA) lidar to measure greenhouse gases, with the goal of measurements from space. Due to the absorption spectrum of CO2 a fiber-based master oscillator power amplifier (MOPA) laser with a tunable seed source is an attractive laser choice. Fiber-based lasers offer a number of potential advantages for space, but since they are relatively new, challenges exist in developing them. In order to reduce risks for new missions using fiber-based lasers, we developed a 30- month plan to mature the technology of a candidate laser transmitter for space-based CO2 measurements to TRL-6. This work is also intended to reduce development time and costs and increase confidence in future mission success

Fiber-Based Laser MOPA Transmitter Packaging for Space Environment

NASAs Goddard Space Flight Center has been developing lidar to remotely measure CO2 and CH4 in the Earths atmosphere. The ultimate goal is to make space-based satellite measurements with global coverage. We are working on maturing the technology readiness of a fiber-based, 1.57-micron wavelength laser transmitter designed for use in atmospheric CO2 remote-sensing. To this end, we are building a ruggedized prototype to demonstrate the required power and performance and survive the required environment. We are building a fiber-based master oscillator power amplifier (MOPA) laser transmitter architecture. The laser is a wavelength-locked, single frequency, externally modulated DBR operating at 1.57-micron followed by erbium-doped fiber amplifiers. The last amplifier stage is a polarization-maintaining, very-large-mode-area fiber with ~1000 m2 effective area pumped by a Raman fiber laser. The optical output is single-frequency, one microsecond pulses with >450 J pulse energy, 7.5 KHz repetition rate, single spatial mode, and > 20 dB polarization extinction

F901318 represents a novel class of antifungal drug that inhibits dihydroorotate dehydrogenase

There is an important medical need for new antifungal agents with novel mechanisms of action to treat the increasing number of patients with life-threatening systemic fungal disease and to overcome the growing problem of resistance to current therapies. F901318, the leading representative of a novel class of drug, the orotomides, is an antifungal drug in clinical development that demonstrates excellent potency against a broad range of dimorphic and filamentous fungi. In vitro susceptibility testing of F901318 against more than 100 strains from the four main pathogenic Aspergillus spp. revealed minimal inhibitory concentrations of ≤0.06 µg/mL—greater potency than the leading antifungal classes. An investigation into the mechanism of action of F901318 found that it acts via inhibition of the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) in a fungal-specific manner. Homology modeling of Aspergillus fumigatus DHODH has identified a predicted binding mode of the inhibitor and important interacting amino acid residues. In a murine pulmonary model of aspergillosis, F901318 displays in vivo efficacy against a strain of A. fumigatus sensitive to the azole class of antifungals and a strain displaying an azole-resistant phenotype. F901318 is currently in late Phase 1 clinical trials, offering hope that the antifungal armamentarium can be expanded to include a class of agent with a mechanism of action distinct from currently marketed antifungals

Human Female Genital Tract Infection by the Obligate Intracellular Bacterium Chlamydia trachomatis Elicits Robust Type 2 Immunity

While Chlamydia trachomatis infections are frequently asymptomatic, mechanisms that regulate host response to this intracellular Gram-negative bacterium remain undefined. This investigation thus used peripheral blood mononuclear cells and endometrial tissue from women with or without Chlamydia genital tract infection to better define this response. Initial genome-wide microarray analysis revealed highly elevated expression of matrix metalloproteinase 10 and other molecules characteristic of Type 2 immunity (e.g., fibrosis and wound repair) in Chlamydia-infected tissue. This result was corroborated in flow cytometry and immunohistochemistry studies that showed extant upper genital tract Chlamydia infection was associated with increased co-expression of CD200 receptor and CD206 (markers of alternative macrophage activation) by endometrial macrophages as well as increased expression of GATA-3 (the transcription factor regulating TH2 differentiation) by endometrial CD4+ T cells. Also among women with genital tract Chlamydia infection, peripheral CD3+ CD4+ and CD3+ CD4- cells that proliferated in response to ex vivo stimulation with inactivated chlamydial antigen secreted significantly more interleukin (IL)-4 than tumor necrosis factor, interferon-γ, or IL-17; findings that repeated in T cells isolated from these same women 1 and 4 months after infection had been eradicated. Our results thus newly reveal that genital infection by an obligate intracellular bacterium induces polarization towards Type 2 immunity, including Chlamydia-specific TH2 development. Based on these findings, we now speculate that Type 2 immunity was selected by evolution as the host response to C. trachomatis in the human female genital tract to control infection and minimize immunopathological damage to vital reproductive structures. © 2013 Vicetti Miguel et al