Coded Aperture Imaging: novel approaches to high-energy high-resolution laboratory imaging

Rapid advancement is being made in laser driven x-ray and particle sources, pushing the boundaries in temporal duration, spatial and spectral distribution, and maximum energy. These advancements need to be complimented with development of imaging capabilities, in order to fully characterise and utilise the new source potential. Here, coded apertures are used to investigate novel approaches to high-energy high-resolution aperture based imaging. Firstly, coded aperture theory is applied to high-energy x-ray sources such as those generated using laser wakefield techniques. The coded aperture is compared to a single pinhole aperture, to discuss whether the prior assumption of highly attenuating substrates is required when using coded apertures. The coded aperture with scatter and partial attenuation included, dubbed a `CASPA', is demonstrated with a 511 keV source simulation, showing that the fully attenuating 18~mm thick tungsten substrate for a single pinhole can be replaced with a 250 um thick tungsten CASPA. Furthermore, the thin CASPA is not mechanism specific, and the physical processes behind the scatter and partial attenuation is found to be inconsequential as long as the combined result yields adequate hologram contrast for image decoding to occur. Secondly, an investigation is conducted into imaging with spectral and spatial information for applications such as laser-solid interaction hotspots. Combing coded apertures with Ross pair filters, a banded spectrally-resolving coded aperture is discussed, dubbed a `BaSCA', using multiple non-redundant array designs on a single aperture and single non-spectrally resolving detector. Finally, the application of a CASPA for imaging high-resolution high-energy neutron sources from inertial confinement fusion experiments is discussed. Using the National Ignition Facility at Lawrence Livermore National Laboratory as an example, a CASPA is designed for the 14.1 MeV neutrons, and reconstruction techniques discussed. In comparison to the currently implemented 20 cm thick gold grand array, it is suggested here that a 10 mm tungsten CASPA would suffice - potentially reducing manufacturing costs, increasing ease of implementation and field of view

Forelimb-Hindlimb Developmental Timing Changes across Tetrapod Phylogeny

Background: Tetrapods exhibit great diversity in limb structures among species and also between forelimbs and hindlimbs within species, diversity which frequently correlates with locomotor modes and life history. We aim to examine the potential relation of changes in developmental timing (heterochrony) to the origin of limb morphological diversity in an explicit comparative and quantitative framework. In particular, we studied the relative time sequence of development of the forelimbs versus the hindlimbs in 138 embryos of 14 tetrapod species spanning a diverse taxonomic, ecomorphological and life-history breadth. Whole-mounts and histological sections were used to code the appearance of 10 developmental events comprising landmarks of development from the early bud stage to late chondrogenesis in the forelimb and the corresponding serial homologues in the hindlimb. Results: An overall pattern of change across tetrapods can be discerned and appears to be relatively clade-specific. In the primitive condition, as seen in Chondrichthyes and Osteichthyes, the forelimb/pectoral fin develops earlier than the hindlimb/pelvic fin. This pattern is either retained or re-evolved in eulipotyphlan insectivores (= shrews, moles, hedgehogs, and solenodons) and taken to its extreme in marsupials. Although exceptions are known, the two anurans we examined reversed the pattern and displayed a significant advance in hindlimb development. All other species examined, including a bat with its greatly enlarged forelimbs modified as wings in the adult, showed near synchrony in the development of the fore and hindlimbs. Conclusion: Major heterochronic changes in early limb development and chondrogenesis were absent within major clades except Lissamphibia, and their presence across vertebrate phylogeny are not easily correlated with adaptive phenomena related to morphological differences in the adult fore- and hindlimbs. The apparently conservative nature of this trait means that changes in chondrogenetic patterns may serve as useful phylogenetic characters at higher taxonomic levels in tetrapods. Our results highlight the more important role generally played by allometric heterochrony in this instance to shape adult morphology.Organismic and Evolutionary Biolog

Advancement of the 5-Amino-1-(Carbamoylmethyl)-1H-1,2,3-Triazole-4-Carboxamide Scaffold to Disarm the Bacterial SOS Response

Many antibiotics, either directly or indirectly, cause DNA damage thereby activating the bacterial DNA damage (SOS) response. SOS activation results in expression of genes involved in DNA repair and mutagenesis, and the regulation of the SOS response relies on two key proteins, LexA and RecA. Genetic studies have indicated that inactivating the regulatory proteins of this response sensitizes bacteria to antibiotics and slows the appearance of resistance. However, advancement of small molecule inhibitors of the SOS response has lagged, despite their clear promise in addressing the threat of antibiotic resistance. Previously, we had addressed this deficit by performing a high throughput screen of ∼1.8 million compounds that monitored for inhibition of RecA-mediated auto-proteolysis of Escherichia coli LexA, the reaction that initiates the SOS response. In this report, the refinement of the 5-amino-1-(carbamoylmethyl)-1H-1,2,3-triazole-4-carboxamide scaffold identified in the screen is detailed. After development of a modular synthesis, a survey of key activity determinants led to the identification of an analog with improved potency and increased breadth, targeting auto-proteolysis of LexA from both E. coli and Pseudomonas aeruginosa. Comparison of the structure of this compound to those of others in the series suggests structural features that may be required for activity and cross-species breadth. In addition, the feasibility of small molecule modulation of the SOS response was demonstrated in vivo by the suppression of the appearance of resistance. These structure activity relationships thus represent an important step toward producing Drugs that Inhibit SOS Activation to Repress Mechanisms Enabling Resistance (DISARMERs)

Triage tests for identifying atrial fibrillation in primary care : a diagnostic accuracy study comparing single-lead ECG and modified BP monitors

Objective New electronic devices offer an opportunity within routine primary care settings for improving the detection of atrial fibrillation (AF), which is a common cardiac arrhythmia and a modifiable risk factor for stroke. We aimed to assess the performance of a modified blood pressure (BP) monitor and two single-lead ECG devices, as diagnostic triage tests for the detection of AF. Setting 6 General Practices in the UK. Participants 1000 ambulatory patients aged 75 years and over. Primary and secondary outcome measures Comparative diagnostic accuracy of modified BP monitor and single-lead ECG devices, compared to reference standard of 12-lead ECG, independently interpreted by cardiologists. Results A total of 79 participants (7.9%) had AF diagnosed by 12-lead ECG. All three devices had a high sensitivity (93.9–98.7%) and are useful for ruling out AF. WatchBP is a better triage test than Omron autoanalysis because it is more specific—89.7% (95% CI 87.5% to 91.6%) compared to 78.3% (95% CI 73.0% to 82.9%), respectively. This would translate into a lower follow-on ECG rate of 17% to rule in/rule out AF compared to 29.7% with the Omron text message in the study population. The overall specificity of single-lead ECGs analysed by a cardiologist was 94.6% for Omron and 90.1% for Merlin. Conclusions WatchBP performs better as a triage test for identifying AF in primary care than the single-lead ECG monitors as it does not require expertise for interpretation and its diagnostic performance is comparable to single-lead ECG analysis by cardiologists. It could be used opportunistically to screen elderly patients for undiagnosed AF at regular intervals and/or during BP measurement

Forelimb-Hindlimb Developmental Timing Changes across Tetrapod Phylogeny

Tetrapods exhibit great diversity in limb structures among species and also between forelimbs and hindlimbs within species, diversity which frequently correlates with locomotor modes and life history. We aim to examine the potential relation of changes in developmental timing (heterochrony) to the origin of limb morphological diversity in an explicit comparative and quantitative framework. In particular, we studied the relative time sequence of development of the forelimbs versus the hindlimbs in 138 embryos of 14 tetrapod species spanning a diverse taxonomic, ecomorphological and life-history breadth. Whole- mounts and histological sections were used to code the appearance of 10 developmental events comprising landmarks of development from the early bud stage to late chondrogenesis in the forelimb and the corresponding serial homologues in the hindlimb. Results: An overall pattern of change across tetrapods can be discerned and appears to be relatively clade- specific. In the primitive condition, as seen in Chondrichthyes and Osteichthyes, the forelimb/ pectoral fin develops earlier than the hindlimb/ pelvic fin. This pattern is either retained or re- evolved in eulipotyphlan insectivores (= shrews, moles, hedgehogs, and solenodons) and taken to its extreme in marsupials. Although exceptions are known, the two anurans we examined reversed the pattern and displayed a significant advance in hindlimb development. All other species examined, including a bat with its greatly enlarged forelimbs modified as wings in the adult, showed near synchrony in the development of the fore and hindlimbs. Conclusion: Major heterochronic changes in early limb development and chondrogenesis were absent within major clades except Lissamphibia, and their presence across vertebrate phylogeny are not easily correlated with adaptive phenomena related to morphological differences in the adult fore- and hindlimbs. The apparently conservative nature of this trait means that changes in chondrogenetic patterns may serve as useful phylogenetic characters at higher taxonomic levels in tetrapods. Our results highlight the more important role generally played by allometric heterochrony in this instance to shape adult morphology.Geological Science

Niche Markets, Regional Diversification and the Reinvention of Western Australia's Sandalwood Industry

Diversification and niche marketing have become very important economic strategies for many rural small businesses, farmers and communities. As part of these strategies, new opportunities often emerge for traditional products and industries. In the case of Western Australia, this has contributed to the revitalisation of the sandalwood industry. While sandalwood has been exported from Western Australia for more than 150 years, for much of the second half of the twentieth century it was of little economic significance. In recent years, however, the industry has become increasingly entrepreneurial, successfully marketing its products into niche markets in the global economy. For farmers and communities in rural areas, the revitalisation of the sandalwood industry has also provided opportunities for economic diversification and a profitable way of tackling land degradation. Copyright (c) 2003 by the Royal Dutch Geographical Society KNAG.