Stable Integration of Transgenes Delivered by a Retrotransposon–Adenovirus Hybrid Vector

Helper-dependent adenoviruses show great promise as gene delivery vectors. However, because they do not integrate into the host chromosome, transgene expression cannot be maintained indefinitely. To overcome these limitations, we have inserted an L1 retrotransposon/transgene element into a helper-dependent adenovirus to create a novel chimeric gene delivery vector. Efficient adenovirus-mediated delivery of the L1 element into cultured human cells results in subsequent retrotransposition and stable integration of the transgene. L1 retrotransposition frequency was found to correlate with increasing multiplicity of infection by the chimeric vector, and further retrotransposition from newly integrated elements was not observed on prolonged culture. Therefore, this vector, which utilizes components of low immunogenic potential, represents a novel two-stage gene delivery system capable of achieving high titers via the initial helper-dependent adenovirus stage and permanent transgene integration via the retrotransposition stage.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63154/1/104303401750298571.pd

Using screen video capture software to aide and inform cognitive interviewing

Web-based surveys are a salient tool in the repertoire of social and behavioral scientists. The increase in web-based surveys is understandable considering the distinct advantages offered, including: (a) lower costs and reduced labor time, (b) ability to directly transfer data into statistical packages (reducing coding errors), (c) customization options enabling more attractive presentation, (d) ability to reduce respondent burden by embedding skip patterns, and (e) access to larger sample sizes in different geographic regions. It is important to note, however, that administering web-based surveys also introduces distinct sources of error (e.g., coverage, sampling and non-response). Regardless of format (e.g., paper-and-pencil or web-based), specific, prescribed steps must be followed when constructing an instrument in order to reduce survey error and lend credence to the data collected before subsequent analysis is performed. One of those crucial stages integral to the pretesting process is cognitive interviewing. Cognitive interviewing is a qualitative process, encompassing two main techniques: think aloud interviewing and verbal probing. Collectively, these two methods seek to (a) produce information on what the respondent is thinking while answering the questions, (b) the cognitive processes used to answer the questions, and (c) how the respondent answers the questions. The purpose of this article is to provide a practical guide outlining how Camtasia, a screen video capture software, can aide and inform the cognitive interview process

Electric current circuits in astrophysics

Cosmic magnetic structures have in common that they are anchored in a dynamo, that an external driver converts kinetic energy into internal magnetic energy, that this magnetic energy is transported as Poynting fl ux across the magnetically dominated structure, and that the magnetic energy is released in the form of particle acceleration, heating, bulk motion, MHD waves, and radiation. The investigation of the electric current system is particularly illuminating as to the course of events and the physics involved. We demonstrate this for the radio pulsar wind, the solar flare, and terrestrial magnetic storms

Reducing visitor car use in a protected area: A market segmentation approach to achieving behaviour change

This research uses a market segmentation approach to reducing transport-related environmental burdens from visitors, while maintaining economic benefit. The approach was tested in the Lake District National Park (UK). It aimed first to explore visitor transport behaviour using a social psychological framework, to understand what might best predict desired behaviour change (i.e. reduced visitor car use). Second, it developed and tested different types of marketing messages to reduce car use, based on persuasive communication theory, establishing marketing propositions appropriate to different visitor types and market segments. Third, it identified market segments with both a high propensity towards positive behavioural change and the highest economic contribution to the destination. The work is based on Ajzen's Theory of Planned Behaviour and on persuasive communication. Three hundred and ninety completed questionnaires were obtained. The paper emphasises the importance of context in successful communication to influence behaviour and shows that a market segmentation approach to behavioural change can be successful. Complex patterns of visitor mobility and modal choice emerge. For example "New Explorers" and "Familiar Families" are most likely to reduce their car use (45% and 48% respectively) and less likely to perceive this as difficult. © 2013 Taylor & Francis

Space Telescope and Optical Reverberation Mapping Project. VII. Understanding the Ultraviolet Anomaly in NGC 5548 with X-Ray Spectroscopy

During the Space Telescope and Optical Reverberation Mapping Project observations of NGC 5548, the continuum and emission-line variability became decorrelated during the second half of the six-month-long observing campaign. Here we present Swift and Chandra X-ray spectra of NGC 5548 obtained as part of the campaign. The Swift spectra show that excess flux (relative to a power-law continuum) in the soft X-ray band appears before the start of the anomalous emission-line behavior, peaks during the period of the anomaly, and then declines. This is a model-independent result suggesting that the soft excess is related to the anomaly. We divide the Swift data into on- and off-anomaly spectra to characterize the soft excess via spectral fitting. The cause of the spectral differences is likely due to a change in the intrinsic spectrum rather than to variable obscuration or partial covering. The Chandra spectra have lower signal-to-noise ratios, but are consistent with the Swift data. Our preferred model of the soft excess is emission from an optically thick, warm Comptonizing corona, the effective optical depth of which increases during the anomaly. This model simultaneously explains all three observations: the UV emission-line flux decrease, the soft-excess increase, and the emission-line anomaly

Towards global consensus on core outcomes for hidradenitis suppurativa research: an update from the HISTORIC consensus meetings I and II

Background A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed‐upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e‐Delphi surveys. In this manuscript, we describe two in‐person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items. Objectives To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains. Methods The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey. Results Forty‐one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS‐specific quality of life, satisfaction, symptoms, pain and global assessments. Conclusions The HISTORIC consensus meetings I and II will be followed by further e‐Delphi rounds to finalize the core domain set, building on the work of the in‐person consensus meetings

An Observational Overview of Solar Flares

We present an overview of solar flares and associated phenomena, drawing upon a wide range of observational data primarily from the RHESSI era. Following an introductory discussion and overview of the status of observational capabilities, the article is split into topical sections which deal with different areas of flare phenomena (footpoints and ribbons, coronal sources, relationship to coronal mass ejections) and their interconnections. We also discuss flare soft X-ray spectroscopy and the energetics of the process. The emphasis is to describe the observations from multiple points of view, while bearing in mind the models that link them to each other and to theory. The present theoretical and observational understanding of solar flares is far from complete, so we conclude with a brief discussion of models, and a list of missing but important observations.Comment: This is an article for a monograph on the physics of solar flares, inspired by RHESSI observations. The individual articles are to appear in Space Science Reviews (2011