Chiral Thianthrenes

Acknowledgments: We thank the UK EPSRC National Mass Spectrometry Service Centre for mass spectrometric data and the UK National Crystallography Centre (University of Southampton) for the X-ray data collections. M. J. Plater performed all syntheses and obtained the characterisation data, and W. T. A. Harrison solved the crystallographic data sets. Data sets were obtained free of charge from the National Crystallography Centre, Southampton University.Peer reviewe

Uncovering John Holliday’s industrial dye synthesis patented in 1865

Open Access via the Sage Agreement The authors thank the UK Engineering and Physical Sciences Research Council (EPSRC) National Mass Spectrometry Service Centre for mass spectrometric data and the UK National Crystallography Centre (University of Southampton) for the X-ray data collections. Data sets were obtained free of charge from the National Crystallography Centre, Southampton University.Peer reviewedPublisher PD

Micromagnetic simulation of magnetofossils with realistic size and shape distributions: Linking magnetic proxies with nanoscale observations and implications for magnetofossil identification

We build micromagnetic models to investigate the magnetic properties of biogenic magnetite - a common type of magnetic minerals that is responsible for recording a wide range of biological, geophysical and geological processes on earth. The geometry of modelled particles is based on realistic size and shape distributions from nanoscale observations. Systematic changes in microstructures of biogenic magnetite ensembles are built and their magnetic properties are calculated, which enables a quantitative and separate assessment of the effect of crystal morphology and chain structures. Although the same particle size and shape distributions are used in all calculations, simulation results document large variations in magnetic properties, i.e., wide distributions of coercivity (Bc = ~10-60 mT), coercivity of remanence (Bcr = ~14-81 mT), dispersion parameter (DP = ~0.1-0.5), and skewness values (S = ~0.7-1.1) due to variable degree of anisotropy and magnetostatic interactions. Previously, the commonly observed "biogenic soft" and "biogenic hard" components on biogenic magnetite-bearing samples were often interpreted to reflect crystal morphologies, and that the small DP values of coercivity distributions were an indication of narrow particle size distributions. Our simulations suggest that these speculations are not always the case and that magnetosome microstructures likely exert a dominant control over their magnetic properties. Our modelling results provide a new theoretical perspective on the magnetic properties of biogenic magnetite, which is important for understanding magnetic proxy signals from magnetofossils in a wide range of environmental and geological settings, and for the search for biogenic magnetite in terrestrial rocks and in extra-terrestrial materials.European Research Counci

Reactions of 4,5-difluoro-1,2-dinitrobenzene with amines in dimethylformamide or EtOH

Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.Peer reviewedPublisher PD

The pressure of concrete on vertical formwork in wide sections.

A theory is presented which describes the mechanisms involved in concrete pressures on formwork in wide sections. The main value of the theory is in providing a framework for analysing site data and indicating areas in which potential economies in design might be made. The horizontal pressure of concrete on formwork comprises two components whose magnitude depends -on the proportion of the vertical load taken by the particle structure and the pore water pressure. In normal formwork, the pore water pressure provides the major contribution to the maximum horizontal pressure and therefore any factor which increases the rate of load transfer from the pore water pressure onto the particle structure, will decrease the maximum pressure. For example, porous formwork will give lower horizontal pressures than impermeable formwork and the re-analysis of existing site data supports this prediction. Normal internal vibration does not have such a significant' affect on the maximum horizontal pressure as previously reported, but it can fluidify concrete to the depth of poker immersion. The elements of the theory are supported by an experimental programme, re-analysis of existing site data and new site measurements. These site measurements have shown that during underwater concreting a rapidly falling tide can cause the horizontal pressure to exceed the vertical pressure

A Differential Positioning System Using Modulation Correlation of Signals of Opportunity

Global Navigation Satellite Systems (GNSS) have become the positioning systems of choice for many applications. However, GNSS signals are susceptible to obstruction, interference and jamming. Therefore, to maximize robustness and integrity, it is necessary to employ a dissimilar positioning technology that can operate independently and back-up GNSS. One such technology exploits ‘signals of opportunity’ – signals that are designed for purposes other than navigation. This paper presents a system that uses amplitude modulation (AM) radio broadcasts in the medium frequency (MF) band. At these frequencies, the predominant ground-wave propagation mode offers better coverage in remote areas and over sea than is achievable with higher frequency signals. The system is differential and operates by correlating modulation information between the reference and user receivers. A system of this form mitigates the deterioration in and around buildings encountered in prior systems and can provide absolute position using fewer signals than a system using only carrier phase. The system presented in this paper uses generalized cross correlation to obtain time difference of arrival measurements that are subsequently used for position determination. Preliminary results indicate the system provides a robust position solution. Moreover, the system offers the potential to be combined with carrier phase measurements to achieve enhanced performance, while the modulation correlation technique is readily extendable to other types of signal

A New Differential Positioning Method using Modulation Correlation of Signals of Opportunity

Global Navigation Satellite Systems (GNSS) have become the positioning systems of choice for many applications. However, GNSS signals are susceptible to obstruction, interference and jamming. Therefore, to maximize robustness and integrity, it is necessary to employ a dissimilar positioning technology that can operate independently and back-up GNSS. One such technology exploits 'signals of opportunity' - signals that are designed for purposes other than navigation.This paper presents a system that uses amplitude modulation (AM) radio broadcasts in the medium frequency (MF) band. At these frequencies, the predominant ground-wave propagation mode offers better coverage in remote areas and over sea than is achievable with higher frequency signals.The system is differential and operates by correlating modulation information between the reference and user receivers. A system of this form mitigates the deterioration in and around buildings encountered in prior systems and can provide absolute position using fewer signals than a system using only carrier phase.The system presented in this paper uses generalized cross correlation to obtain time difference of arrival measurements that are subsequently used for position determination. Preliminary results indicate the system provides a robust position solution. Moreover, the system offers the potential to be combined with carrier phase measurements to achieve enhanced performance, while the modulation correlation technique is readily extendable to other types of signal

A New Differential Positioning Technique Applicable to Generic FDMA Signals of Opportunity

A differential positioning technique is proposed that is capable of exploiting the many radio frequency (RF) signals that are transmitted using frequency division multiple access (FDMA). The technique is designed to operate on ‘signals of opportunity’ (signals that are designed for purposes other than navigation), and requires no knowledge of the modulation format or signal content. Example FDMA signals of opportunity include amplitude modulated (AM) broadcast signals, frequency modulated (FM) broadcast signals, and television signals. In principle, the system can operate simultaneously on these different types of signals, maximizing performance by exploiting heterogeneous signal qualities and using whatever signals are available at a particular location. As a result, the technology has the potential to provide positioning in Global Navigation Satellite System (GNSS) deprived environments, such as in urban canyons, and deep indoors. The proposed positioning technique operates by bringing portions of a signal received at reference and user locations together and adaptively correlation testing them. The correlation-testing is used to jointly estimate the differential time offset (DTO) and the differential frequency offset (DFO). In order to improve accuracy the DTO measurements are Doppler-smoothed using the DFO measurements. The DTO measurements are used to calculate ranging measurements that are used to obtain a position. The concept is experimentally validated on AM broadcast signals in the medium frequency (MF) and low frequency (LF) bands. Preliminary results indicate that the system provides a position solution in difficult environments, such as indoors. It is expected that expanding the system to incorporate more signals will result in significant performance gains

Combination Therapy for HIV-Associated Cryptococcal Meningitis-A Success Story.

Cryptococcal meningitis is the leading cause of adult meningitis in patients with HIV, and accounts for 15% of all HIV-related deaths in sub-Saharan Africa. The mainstay of management is effective antifungal therapy, despite a limited arsenal of antifungal drugs, significant progress has been made developing effective treatment strategies by using combination regimens. The introduction of fluconazole as a safe and effective step-down therapy allowed for shorter courses of more fungicidal agents to be given as induction therapy, with higher doses achieving more rapid CSF sterilisation and improved treatment outcomes. The development of early fungicidal activity (EFA), an easily measured surrogate of treatment efficacy, has enabled rapid identification of effective combinations through dose ranging phase II studies, allowing further evaluation of clinical benefit in targeted phase III studies. Recent clinical trials have shown that shorter course induction regimens using one week of amphotericin paired with flucytosine are non-inferior to traditional two-week induction regimens and that the combination of fluconazole and flucytosine offers a viable treatment alternative when amphotericin is unavailable. Access to drugs in many low and middle-income settings remains challenging but is improving, and novel strategies based on single high dose liposomal amphotericin B promise further reduction in treatment complications and toxicities. This review aims to summarise the key findings of the principal clinical trials that have led to the success story of combination therapy thus far

A group II metabotropic glutamate receptor 3 (mGlu3, GRM3) isoform implicated in schizophrenia interacts with canonical mGlu3 and reduces ligand binding

As well as being expressed as a full-length transcript, the group II metabotropic glutamate receptor 3 (GRM3, mGlu3) gene is expressed as an mRNA isoform which lacks exon 4 (GRM3Δ4) and which is predicted to encode a protein with a novel C terminus (called mGlu34). This variant may contribute to the mechanism by which GRM3 acts as a schizophrenia risk gene. However, little is known about the properties or function of mGlu3Δ4. Here, using transiently transfected HEK293T/17 cells, we confirm that GRM3Δ4 cDNA is translated, with mGlu3Δ4 existing as a homodimer as well as a monomer, and localising primarily to cell membranes including the plasma membrane. Co-immunoprecipitation shows that mGlu3Δ4 interacts with canonical mGlu3. mGlu3Δ4 does not bind the mGlu2/3 antagonist [3H]LY341495, but the presence of mGlu3Δ4 reduces binding of [3H]LY341495 to mGlu3, paralleled by a decrease in the abundance of membrane-associated mGlu3. These experiments indicate that mGlu3Δ4 may negatively modulate mGlu3, and thereby impact on the roles of GRM3/mGlu3 in schizophrenia and as a therapeutic target