Exploiting the Symmetry of the Resonator Mode to Enhance PELDOR Sensitivity.

Pulsed electron paramagnetic resonance (EPR) spectroscopy using microwaves at two frequencies can be employed to measure distances between pairs of paramagnets separated by up to 10 nm. The method, combined with site-directed mutagenesis, has become increasingly popular in structural biology for both its selectivity and capability of providing information not accessible through more standard methods such as nuclear magnetic resonance and X-ray crystallography. Despite these advantages, EPR distance measurements suffer from poor sensitivity. One contributing factor is technical: since 65 MHz typically separates the pump and detection frequencies, they cannot both be located at the center of the pseudo-Lorentzian microwave resonance of a single-mode resonator. To maximize the inversion efficiency, the pump pulse is usually placed at the center of the resonance, while the observer frequency is placed in the wing, with consequent reduction in sensitivity. Here, we consider an alternative configuration: by spacing pump and observer frequencies symmetrically with respect to the microwave resonance and by increasing the quality factor, valuable improvement in the signal-to-noise ratio can be obtained

Integrating tuberculosis and HIV care in the primary care setting in South Africa.

BACKGROUND: In many countries including South Africa, the increasing human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics have impacted significantly on already weakened public health services. This paper reviews the scope, process and performance of the HIV and TB services in a primary care setting where antiretroviral therapy is provided, in Khayelitsha, South Africa, in order to assess whether there is a need for some form of integration. METHODS: The scope and process of both services were assessed through observations of the service and individual and group interviews with key persons. The performance was assessed by examining the 2001-2002 reports from the health information system and clinical data. RESULTS: The TB service is programme oriented to the attainment of an 85% cure rate amongst smear-positive patients while the HIV service has a more holistic approach to the patient with HIV. The TB service is part of a well-established programme that is highly standardized. The HIV service is in the pilot phase. There is a heavy load at both services and there is large degree of cross-referral between the two services. There are lessons that can be learnt from each service. There is an overlap of activities, duplication of services and under-utilization of staff. There are missed opportunities for TB and HIV prevention, diagnosis and management. CONCLUSIONS: The study suggests that there may be benefits to integrating HIV and TB services. Constraints to this process are discussed

Affective state influences retrieval-induced forgetting for integrated knowledge

Selectively testing parts of learned materials can impair later memory for nontested materials. Research has shown that such retrieval-induced forgetting occurs for low-integrated materials but may be prevented for high-integrated materials. However, previous research has neglected one factor that is ubiquitous in real-life testing: affective stat

When does the algebraic Riccati equation have a negative semi-definite solution?

Find a reasonable necessary and sufficient frequency domain condition, i.e, a condition in terms of the rational matrix ∂W, or possibly in terms of the two-variable rational matrix W, for the existence of a real symmetric negative semi-definite solution of the algebraic Riccati equation

Skewed contributions of individual trees to indirect nature experiences

This is the author accepted manuscript. Final version available from Elsevier via the DOI in this record.Exposure to nature is associated with a broad range of benefits to human health. Whilst there has been exploration of how these experiences vary amongst people, the converse – how different individual organisms contribute to human nature experiences – has largely been overlooked. The most common way that people experience nature occurs indirectly, when they are in a room with a natural view. Here, we estimate variation in how individual trees provide indirect nature experiences in an urban human population. As a proxy for its contribution towards indirect nature experiences, within an extended urban area in southern England, UK (n = 612,920) we calculated the number of buildings with line of sight to each tree. We then modelled each tree’s contribution towards these experiences against potential predictors, namely tree height, land ownership, social deprivation, while controlling for human population density. We demonstrate that a small number of trees contribute disproportionately towards indirect nature experiences, with individual trees in socio-economically deprived high density housing falling within the viewscape of significantly more buildings. Further, trees in private gardens were generally more important for providing indirect nature experiences than those in public green spaces. This novel study demonstrates the skewed contribution of different organisms to human population indirect nature experiences. This approach can be applied more broadly to understand how individual organisms provide indirect, incidental and intentional nature experiences. Understanding the ecology behind human nature experiences is an important step towards linking urban design and policy for maximising the health benefits from nature.Natural Environment Research Council (NERC

One- and two-photon activated phototoxicity of conjugated porphyrin dimers with high two-photon absorption cross sections

Two-photon excited photodynamic therapy (PDT) has the potential to provide a highly targeted treatment for neoplastic diseases, as excitation can be pin-pointed to small volumes at the laser focus. In addition, two-photon PDT offers deeper penetration into mammalian tissue due to the longer wavelength of irradiation. Here we report the one-photon and two-photon excited PDT results for a collection of conjugated porphyrin dimers with high two-photon absorption cross sections. These dimers demonstrate high one-photon PDT efficacy against a human ovarian adenocarcinoma cell line (SK-OV-3) and exhibit no significant dark-toxicity at concentrations of up to 20 microM. Their one-photon excited PDT efficiencies, following irradiation at 657 nm, approach that of Visudyne, a drug used clinically for PDT. We investigated and optimised the effect of the photosensitizer concentration, incubation time and the light dose on the PDT efficacy of these dimers. These studies led to the selection of P2C2-NMeI as the most effective porphyrin dimer. We have demonstrated that P2C2-NMeI undergoes a two-photon activated process following excitation at 920 nm (3.6-6.8 mW, 300 fs, 90 MHz) and compared it to Visudyne. We conclude that the in vitro two-photon PDT efficacy of P2C2-NMeI is about twice that of Visudyne. This result highlights the potential of this series of porphyrin dimers for two-photon PDT

Pulmonary Mycobacterium avium-intracellulare is the main driver of the rise in non-tuberculous mycobacteria incidence in England, Wales and Northern Ireland, 2007-2012

BACKGROUND: The incidence of non-tuberculous mycobacteria (NTM) isolation from humans is increasing worldwide. In England, Wales and Northern Ireland (EW&NI) the reported rate of NTM more than doubled between 1996 and 2006. Although NTM infection has traditionally been associated with immunosuppressed individuals or those with severe underlying lung damage, pulmonary NTM infection and disease may occur in people with no overt immune deficiency. Here we report the incidence of NTM isolation in EW&NI between 2007 and 2012 from both pulmonary and extra-pulmonary samples obtained at a population level. METHODS: All individuals with culture positive NTM isolates between 2007 and 2012 reported to Public Health England by the five mycobacterial reference laboratories serving EW&NI were included. RESULTS: Between 2007 and 2012, 21,118 individuals had NTM culture positive isolates. Over the study period the incidence rose from 5.6/100,000 in 2007 to 7.6/100,000 in 2012 (p < 0.001). Of those with a known specimen type, 90 % were pulmonary, in whom incidence increased from 4.0/100,000 to 6.1/100,000 (p < 0.001). In extra-pulmonary specimens this fell from 0.6/100,000 to 0.4/100,000 (p < 0.001). The most frequently cultured organisms from individuals with pulmonary isolates were within the M. avium-intracellulare complex family (MAC). The incidence of pulmonary MAC increased from 1.3/100,000 to 2.2/100,000 (p < 0.001). The majority of these individuals were over 60 years old. CONCLUSION: Using a population-based approach, we find that the incidence of NTM has continued to rise since the last national analysis. Overall, this represents an almost ten-fold increase since 1995. Pulmonary MAC in older individuals is responsible for the majority of this change. We are limited to reporting NTM isolates and not clinical disease caused by these organisms. To determine whether the burden of NTM disease is genuinely increasing, a standardised approach to the collection of linked national microbiological and clinical data is required

Towards efficient near-infrared fluorescent organic light-emitting diodes

The energy gap law (EG-law) and aggregation quenching are the main limitations to overcome in the design of near-infrared (NIR) organic emitters. Here, we achieve unprecedented results by synergistically addressing both of these limitations. First, we propose porphyrin oligomers with increasing length to attenuate the effects of the EG -law by suppressing the non-radiative rate growth, and to increase the radiative rate via enhancement of the oscillator strength. Second, we design side chains to suppress aggregation quenching. We find that the logarithmic rate of variation in the non-radiative rate vs. EG is suppressed by an order of magnitude with respect to previous studies, and we complement this breakthrough by demonstrating organic light-emitting diodes with an average external quantum efficiency of ~1.1%, which is very promising for a heavy-metal-free 850 nm emitter. We also present a novel quantitative model of the internal quantum efficiency for active layers supporting triplet-to-singlet conversion. These results provide a general strategy for designing high-luminance NIR emitters

Doses of neighborhood nature: the benefits for mental health of living with nature

This is the author accepted manuscript. The final version is available from OUP via the DOI in this record.Experiences of nature provide many mental health benefits, particularly for people living in urban areas. The natural characteristics of city residents’ neighborhoods are likely to be critical determinants of the daily nature dose that they receive, however which characteristics are important remains unclear. One possibility is that the greatest benefits are provided by characteristics that are most visible during the day and so most likely to be experienced by people. We demonstrate that of five neighborhood nature characteristics tested, vegetation cover and afternoon bird abundances were positively associated with a lower prevalence of depression, anxiety and stress. Further, dose-response modelling shows a threshold response where the population prevalence of mental health issues is significantly lower beyond minimum limits of neighborhood vegetation cover (depression >20% cover, anxiety >30% cover, stress >20% cover). Our findings demonstrate quantifiable associations of mental health with the characteristics of nearby nature that people actually experience