Europium-155 as a source for dual energy cone beam computed tomography in adaptive proton therapy: A simulation study

To investigate the feasibility of a 3D imaging system utilizing a 155 Eu source and pixelated cadmium-zinc-telluride (CZT) detector for applications in adaptive radiotherapy. Specifically, to compare the reconstructed stopping power ratio (SPR) values of a head phantom obtained with the proposed imaging technique with theoretical SPR values.A Geant4 Monte Carlo simulation was performed with the novel imaging system. The simulation was repeated with a typical 120 kV X-ray tube spectrum while maintaining all other parameters. Dual energy 155 Eu source cone beam computed tomography (CBCT) images were reconstructed with an iterative projection algorithm known as total variation superiorization with diagonally relaxed orthogonal projections (TVS-DROP). Single energy 120 kV source CBCT images were also reconstructed with TVS-DROP. Reconstructed images were converted to SPR with stoichiometric calibration techniques based on ICRU 44 tissues. Quantitative accuracy of reconstructed attenuation coefficient images as well as SPR images were compared.Images generated by gamma emissions of 155 Eu showed superior contrast resolution to those generated by the 120 kV spectrum. Quantitatively, all reconstructed images correlated with reference attenuation coefficients of the head phantom within 1 standard deviation. Images generated with the 155 Eu source showed a smaller standard deviation of pixel values. Use of a dual energy conversion into SPR resulted in superior SPR accuracy with the 155 Eu source.155 Eu was found to display desirable qualities when used as a source for dual energy CBCT. Further work is required to demonstrate whether the simulation results presented here can be translated into an experimental prototype.Jiahua Zhu, Scott N. Penfol

The atm-1 gene is required for genome stability in Caenorhabditis elegans

The Ataxia-telangiectasia-mutated (ATM) gene in humans was identified as the basis of a rare autosomal disorder leading to cancer susceptibility and is now well known as an important signal transducer in response to DNA damage. An approach to understanding the conserved functions of this gene is provided by the model system, Caenorhabditis elegans. In this paper we describe the structure and loss of function phenotype of the ortholog atm-1. Using bioinformatic and molecular analysis we show that the atm-1 gene was previously misannotated. We find that the transcript is in fact a product of three gene predictions, Y48G1BL.2 (atm-1), K10E9.1, and F56C11.4 that together make up the complete coding region of ATM-1. We also characterize animals that are mutant for two available knockout alleles, gk186 and tm5027. As expected, atm-1 mutant animals are sensitive to ionizing radiation. In addition, however, atm-1 mutants also display phenotypes associated with genomic instability, including low brood size, reduced viability and sterility. We document several chromosomal fusions arising from atm-1 mutant animals. This is the first time a mutator phenotype has been described for atm-1 in C. elegans. Finally we demonstrate the use of a balancer system to screen for and capture atm-1-derived mutational events. Our study establishes C. elegans as a model for the study of ATM as a mutator potentially leading to the development of screens to identify therapeutic targets in humans

Dynamic control of posture across locomotor tasks

Successful locomotion depends on postural control to establish and maintain appropriate postural orientation of body segments relative to one another and to the environment, and to ensure dynamic stability of the moving body. This paper provides a framework for considering dynamic postural control, highlighting the importance of coordination, consistency, and challenges to postural control posed by various locomotor tasks such as turning and backward walking. The impacts of aging and various movement disorders on postural control are discussed broadly in an effort to provide a general overview of the field and recommendations for assessment of dynamic postural control across different populations in both clinical and research settings. Suggestions for future research on dynamic postural control during locomotion are also provided and include discussion of opportunities afforded by new and developing technologies, the need for long-term monitoring of locomotor performance in everyday activities, gaps in our knowledge of how targeted intervention approaches modify dynamic postural control, and the relative paucity of literature regarding dynamic postural control in movement disorder populations other than Parkinson disease

Nominal Henkin Semantics: simply-typed lambda-calculus models in nominal sets

We investigate a class of nominal algebraic Henkin-style models for the simply typed lambda-calculus in which variables map to names in the denotation and lambda-abstraction maps to a (non-functional) name-abstraction operation. The resulting denotations are smaller and better-behaved, in ways we make precise, than functional valuation-based models. Using these new models, we then develop a generalisation of \lambda-term syntax enriching them with existential meta-variables, thus yielding a theory of incomplete functions. This incompleteness is orthogonal to the usual notion of incompleteness given by function abstraction and application, and corresponds to holes and incomplete objects.Comment: In Proceedings LFMTP 2011, arXiv:1110.668

Caenorhabditis elegans Genomic Response to Soil Bacteria Predicts Environment-Specific Genetic Effects on Life History Traits

With the post-genomic era came a dramatic increase in high-throughput technologies, of which transcriptional profiling by microarrays was one of the most popular. One application of this technology is to identify genes that are differentially expressed in response to different environmental conditions. These experiments are constructed under the assumption that the differentially expressed genes are functionally important in the environment where they are induced. However, whether differential expression is predictive of functional importance has yet to be tested. Here we have addressed this expectation by employing Caenorhabditis elegans as a model for the interaction of native soil nematode taxa and soil bacteria. Using transcriptional profiling, we identified candidate genes regulated in response to different bacteria isolated in association with grassland nematodes or from grassland soils. Many of the regulated candidate genes are predicted to affect metabolism and innate immunity suggesting similar genes could influence nematode community dynamics in natural systems. Using mutations that inactivate 21 of the identified genes, we showed that most contribute to lifespan and/or fitness in a given bacterial environment. Although these bacteria may not be natural food sources for C. elegans, we show that changes in food source, as can occur in environmental disturbance, can have a large effect on gene expression, with important consequences for fitness. Moreover, we used regression analysis to demonstrate that for many genes the degree of differential gene expression between two bacterial environments predicted the magnitude of the effect of the loss of gene function on life history traits in those environments

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Betriebliche Umsetzung der 38,5-Stunden-Woche Ergebnisse einer Auswertung von Betriebsvereinbarungen aus der Metallindustrie. Zwischenbericht des Projekts 'Umsetzung der Arbeitszeitverkuerzung'

IAB-90-0BD0-205400 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman