A Streamlined Strategy for Aglycone Assembly and Glycosylation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102108/1/ange_201307680_sm_miscellaneous_information.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102108/2/13892_ftp.pd

Complex roles of myoglianin in regulating adult performance and lifespan

Myoglianin, the Drosophila homolog of the secreted vertebrate proteins Myostatin and GDF-11, is an important regulator of neuronal modelling, and synapse function and morphology. While Myoglianin suppression during development elicits positive effects on the neuromuscular system, genetic manipulations of myoglianin expression levels have a varied effect on the outcome of performance tests in aging flies. Specifically, Myoglianin preserves jumping ability, has no effect on negative geotaxis, and negatively regulates flight performance in aging flies. In addition, Myoglianin exhibits a tissue-specific effect on longevity, with myoglianin upregulation in glial cells increasing the median lifespan. These findings indicate complex role for this TGF-β-like protein in governing neuromuscular signalling and consequent behavioural outputs and lifespan in adult flies

A Streamlined Strategy for Aglycone Assembly and Glycosylation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102092/1/13647_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102092/2/anie_201307680_sm_miscellaneous_information.pd

Dissecting the regulatory activity and sequence content of loci with exceptional numbers of transcription factor associations

DNA-associated proteins (DAPs) classically regulate gene expression by binding to regulatory loci such as enhancers or promoters. As expanding catalogs of genome-wide DAP binding maps reveal thousands of loci that, unlike the majority of conventional enhancers and promoters, associate with dozens of different DAPs with apparently little regard for motif preference, an understanding of DAP association and coordination at such regulatory loci is essential to deciphering how these regions contribute to normal development and disease. In this study, we aggregated publicly available ChIP-seq data from 469 human DAPs assayed in three cell lines and integrated these data with an orthogonal data set of 352 nonredundant, in vitro–derived motifs mapped to the genome within DNase I hypersensitivity footprints to characterize regions with high numbers of DAP associations. We establish a generalizable definition for high occupancy target (HOT) loci and identify putative driver DAP motifs in HepG2 cells, including HNF4A, SP1, SP5, and ETV4, that are highly prevalent and show sequence conservation at HOT loci. The number of different DAPs associated with an element is positively associated with evidence of regulatory activity, and by systematically mutating 245 HOT loci with a massively parallel mutagenesis assay, we localized regulatory activity to a central core region that depends on the motif sequences of our previously nominated driver DAPs. In sum, this work leverages the increasingly large number of DAP motif and ChIP-seq data publicly available to explore how DAP associations contribute to genome-wide transcriptional regulation

Clinical implications of the anisotropic analytical algorithm for IMRT treatment planning and verification

PURPOSE: To determine the implications of the use of the Anisotropic Analytical Algorithm(AAA) for the production and dosimetric verification of IMRT plans for treatments of the prostate, parotid, nasopharynx and lung. METHODS: 72 IMRT treatment plans produced using the Pencil Beam Convolution (PBC)algorithm were recalculated using the AAA and the dose distributions compared. 24 of the plans were delivered to inhomogeneous phantoms and verification measurements made using a pinpoint ionisation chamber. The agreement between the AAA and measurement was determined. RESULTS: Small differences were seen in the prostate plans, with the AAA predicting slightly lower minimum PTV doses. In the parotid plans, there were small increases in the lens and contralateral parotid doses while the nasopharyngeal plans revealed a reduction in the volume of the PTV covered by the 95% isodose (the V95%) when the AAA was used. Large changes were seen in the lung plans, the AAA predicting reductions in the minimum PTV dose and large reductions in the V95%. The AAA also predicted small increases in the mean dose to the normal lung and the V20. In the verification measurements, all AAA calculations were within 3% or 3.5mm distance to agreement of the measured doses. Conclusions: The AAA should be used in preference to the PBC algorithm for treatments involving low density tissue but this may necessitate re-evaluation of plan acceptability criteria. Improvements to the Multi-Resolution Dose Calculation algorithm used in the inverse planning are required to reduce the convergence error in the presence of lung tissue. There was excellent agreement between the AAA and verification measurements for all sites

The TiM system: developing a novel telehealth service to improve access to specialist care in motor neurone disease using user-centered design

Objectives: Attendance at a specialist multidisciplinary motor neurone disease (MND) clinic is associated with improved survival and may also improve quality of life and reduce hospital admissions. However, patients struggle to travel to clinic and may experience difficulties between clinic visits that may not be addressed in a timely manner. We wanted to explore how we could improve access to specialist MND care. Methods: We adopted an iterative, user-centered co-design approach, collaborating with those with experience of providing and receiving MND care including patients, carers, clinicians, and technology developers. We explored the unmet needs of those living with MND, how they might be met through service redesign and through the use of digital technologies. We developed a new digital solution and performed initial testing with potential users including clinicians, patients, and carers. Results: We used these findings to develop a telehealth system (TiM) using an Android app into which patients and carers answer a series of questions about their condition on a weekly basis. The questions aim to capture all the physical, emotional, and social difficulties associated with MND. This information is immediately uploaded to the internet for review by the MND team. The data undergoes analysis in order to alert clinicians to any changes in a patient or carer’s condition. Conclusions: We describe the benefits of developing a novel digitally enabled service underpinned by participatory design. Future trials must evaluate the feasibility and acceptability of the TiM system within a clinical environment

Inner Space/Outer Space:Terence McKenna’s Jungian Psychedelic Ufology

This article discusses the relationship between “inner space” (the mind/consciousness) and perceptions of “outer space” (the extraterrestrial) in Western psychedelic cultures. In particular, it analyses the writings and lectures of Terence McKenna, the most influential psychedelic thinker since the 1960s. Assimilating a broad range of ideas taken from esotericism, shamanism, and science fiction, McKenna became the principal architect of an occult theory of psychedelic experiences referred to here as “psychedelic ufology.” The article further argues that McKenna was formatively influenced by the ideas of Carl Jung and that, as such, subsequent psychedelic ufology tends to be Jungian

Observing the Evolution of the Universe

How did the universe evolve? The fine angular scale (l>1000) temperature and polarization anisotropies in the CMB are a Rosetta stone for understanding the evolution of the universe. Through detailed measurements one may address everything from the physics of the birth of the universe to the history of star formation and the process by which galaxies formed. One may in addition track the evolution of the dark energy and discover the net neutrino mass. We are at the dawn of a new era in which hundreds of square degrees of sky can be mapped with arcminute resolution and sensitivities measured in microKelvin. Acquiring these data requires the use of special purpose telescopes such as the Atacama Cosmology Telescope (ACT), located in Chile, and the South Pole Telescope (SPT). These new telescopes are outfitted with a new generation of custom mm-wave kilo-pixel arrays. Additional instruments are in the planning stages.Comment: Science White Paper submitted to the US Astro2010 Decadal Survey. Full list of 177 author available at http://cmbpol.uchicago.ed