Optimizing dual energy cone beam CT protocols for preclinical imaging and radiation research

Objective: The aim of this work was to investigate whether quantitative dual-energy CT (DECT) imaging is feasible for small animal irradiators with an integrated cone-beam CT (CBCT) system. Methods: The optimal imaging protocols were determined by analyzing different energy combinations and dose levels. The influence of beam hardening effects and the performance of a beam hardening correction (BHC) were investigated. In addition, two systems from different manufacturers were compared in terms of errors in the extracted effective atomic numbers (Z(eff)) and relative electron densities (rho(e)) for phantom inserts with known elemental compositions and relative electron densities. Results: The optimal energy combination was determined to be 50 and 90kVp. For this combination, Z(eff) and r rho(e) can be extracted with a mean error of 0.11 and 0.010, respectively, at a dose level of 60cGy. Conclusion: Quantitative DECT imaging is feasible for small animal irradiators with an integrated CBCT system. To obtain the best results, optimizing the imaging protocols is required. Well-separated X-ray spectra and a sufficient dose level should be used to minimize the error and noise for Z(eff) and rho(e). When no BHC is applied in the image reconstruction, the size of the calibration phantom should match the size of the imaged object to limit the influence of beam hardening effects. No significant differences in Z(eff) and rho(e) errors are observed between the two systems from different manufacturers. Advances in knowledge: This is the first study that investigates quantitative DECT imaging for small animal irradiators with an integrated CBCT system

Large-scale genetic variation of the symbiosis-required megaplasmid pSymA revealed by comparative genomic analysis of Sinorhizobium meliloti natural strains

BACKGROUND: Sinorhizobium meliloti is a soil bacterium that forms nitrogen-fixing nodules on the roots of leguminous plants such as alfalfa (Medicago sativa). This species occupies different ecological niches, being present as a free-living soil bacterium and as a symbiont of plant root nodules. The genome of the type strain Rm 1021 contains one chromosome and two megaplasmids for a total genome size of 6 Mb. We applied comparative genomic hybridisation (CGH) on an oligonucleotide microarrays to estimate genetic variation at the genomic level in four natural strains, two isolated from Italian agricultural soil and two from desert soil in the Aral Sea region. RESULTS: From 4.6 to 5.7 percent of the genes showed a pattern of hybridisation concordant with deletion, nucleotide divergence or ORF duplication when compared to the type strain Rm 1021. A large number of these polymorphisms were confirmed by sequencing and Southern blot. A statistically significant fraction of these variable genes was found on the pSymA megaplasmid and grouped in clusters. These variable genes were found to be mainly transposases or genes with unknown function. CONCLUSION: The obtained results allow to conclude that the symbiosis-required megaplasmid pSymA can be considered the major hot-spot for intra-specific differentiation in S. meliloti

Characterization of spindle checkpoint kinase Mps1 reveals domain with functional and structural similarities to tetratricopeptide repeat motifs of Bub1 and BubR1 checkpoint kinases.

Kinetochore targeting of the mitotic kinases Bub1, BubR1, and Mps1 has been implicated in efficient execution of their functions in the spindle checkpoint, the self-monitoring system of the eukaryotic cell cycle that ensures chromosome segregation occurs with high fidelity. In all three kinases, kinetochore docking is mediated by the N-terminal region of the protein. Deletions within this region result in checkpoint failure and chromosome segregation defects. Here, we use an interdisciplinary approach that includes biophysical, biochemical, cell biological, and bioinformatics methods to study the N-terminal region of human Mps1. We report the identification of a tandem repeat of the tetratricopeptide repeat (TPR) motif in the N-terminal kinetochore binding region of Mps1, with close homology to the tandem TPR motif of Bub1 and BubR1. Phylogenetic analysis indicates that TPR Mps1 was acquired after the split between deutorostomes and protostomes, as it is distinguishable in chordates and echinoderms. Overexpression of TPR Mps1 resulted in decreased efficiency of both chromosome alignment and mitotic arrest, likely through displacement of endogenous Mps1 from the kinetochore and decreased Mps1 catalytic activity. Taken together, our multidisciplinary strategy provides new insights into the evolution, structural organization, and function of Mps1 N-terminal region

Why, what, and how? case study on law, risk, and decision making as necessary themes in built environment teaching

The paper considers (and defends) the necessity of including legal studies as a core part of built environment undergraduate and postgraduate curricula. The writer reflects upon his own experience as a lawyer working alongside and advising built environment professionals in complex land remediation and site safety management situations in the United Kingdom and explains how themes of liability, risk, and decision making can be integrated into a practical simulation in order to underpin more traditional lecture-based law teaching. Through reflection upon the writer's experiments with simulation-based teaching, the paper suggests some innovations that may better orientate law teaching to engage these themes and, thereby, enhance the relevance of law studies to the future needs of built environment professionals in practice.</p

A small protein coded within the mitochondrial canonical gene nd4 regulates mitochondrial bioenergetics

BACKGROUND: Mitochondria have a central role in cellular functions, aging, and in certain diseases. They possess their own genome, a vestige of their bacterial ancestor. Over the course of evolution, most of the genes of the ancestor have been lost or transferred to the nucleus. In humans, the mtDNA is a very small circular molecule with a functional repertoire limited to only 37 genes. Its extremely compact nature with genes arranged one after the other and separated by short non-coding regions suggests that there is little room for evolutionary novelties. This is radically different from bacterial genomes, which are also circular but much larger, and in which we can find genes inside other genes. These sequences, different from the reference coding sequences, are called alternatives open reading frames or altORFs, and they are involved in key biological functions. However, whether altORFs exist in mitochondrial protein-coding genes or elsewhere in the human mitogenome has not been fully addressed. RESULTS: We found a downstream alternative ATG initiation codon in the + 3 reading frame of the human mitochondrial nd4 gene. This newly characterized altORF encodes a 99-amino-acid-long polypeptide, MTALTND4, which is conserved in primates. Our custom antibody, but not the pre-immune serum, was able to immunoprecipitate MTALTND4 from HeLa cell lysates, confirming the existence of an endogenous MTALTND4 peptide. The protein is localized in mitochondria and cytoplasm and is also found in the plasma, and it impacts cell and mitochondrial physiology. CONCLUSIONS: Many human mitochondrial translated ORFs might have so far gone unnoticed. By ignoring mtaltORFs, we have underestimated the coding potential of the mitogenome. Alternative mitochondrial peptides such as MTALTND4 may offer a new framework for the investigation of mitochondrial functions and diseases

The structure of causal sets

More often than not, recently popular structuralist interpretations of physical theories leave the central concept of a structure insufficiently precisified. The incipient causal sets approach to quantum gravity offers a paradigmatic case of a physical theory predestined to be interpreted in structuralist terms. It is shown how employing structuralism lends itself to a natural interpretation of the physical meaning of causal sets theory. Conversely, the conceptually exceptionally clear case of causal sets is used as a foil to illustrate how a mathematically informed rigorous conceptualization of structure serves to identify structures in physical theories. Furthermore, a number of technical issues infesting structuralist interpretations of physical theories such as difficulties with grounding the identity of the places of highly symmetrical physical structures in their relational profile and what may resolve these difficulties can be vividly illustrated with causal sets.Comment: 19 pages, 4 figure

In the dark in a large urban park: DNA barcodes illuminate cryptic and introduced moth species

Abstract To facilitate future assessments of diversity following disturbance events, we conducted a first level inventory of nocturnal Lepidoptera in Stanley Park, Vancouver, Canada. To aid the considerable task, we employed high-throughput DNA barcoding for the rough sorting of all material and for tentative species identifications, where possible. We report the preliminary species list of 190, the detection of four new exotic species (Argyresthia pruniella, Dichelia histrionana, Paraswammerdamia lutarea, and Prays fraxinella), and the potential discovery of two cryptic species. We describe the magnitude of assistance that barcoding presents for faunal inventories, from reducing specialist time to facilitating the detection of native and exotic species at low density

Upper limits on the strength of periodic gravitational waves from PSR J1939+2134

The first science run of the LIGO and GEO gravitational wave detectors presented the opportunity to test methods of searching for gravitational waves from known pulsars. Here we present new direct upper limits on the strength of waves from the pulsar PSR J1939+2134 using two independent analysis methods, one in the frequency domain using frequentist statistics and one in the time domain using Bayesian inference. Both methods show that the strain amplitude at Earth from this pulsar is less than a few times $10^{-22}$.Comment: 7 pages, 1 figure, to appear in the Proceedings of the 5th Edoardo Amaldi Conference on Gravitational Waves, Tirrenia, Pisa, Italy, 6-11 July 200