Self-assembly of ssDNA-amphiphiles into micelles, nanotapes and nanotubes

University of Minnesota Ph.D. dissertation. December 2014. Major: Biomedical Engineering. Advisor: Efrosini Kokkoli. 1 computer file (PDF); x, 97 pages.The field of DNA nanotechnology utilizes DNA as a construction material to create functional supramolecular and multi-dimensional structures like two-dimensional periodic lattices and three-dimensional polyhedrons with order on the nanometer scale for many nanotechnology applications including molecular templating, nanosensors, and drug delivery. Single-stranded DNA (ssDNA) is often used to create these nanostructures as the DNA bases provide an intrinsic molecular code that can be exploited to allow for the programmed assembly of structures based upon Watson-Crick base-pairing. However, engineering these complex structures from biopolymers alone requires careful design to ensure that the intrinsic forces responsible for organizing the materials can produce the desired structures. Additional control over supramolecular assembly can be achieved by chemically modifying the ssDNA with hydrophobic moieties to create amphiphilic molecules, which adds the hydrophobic interaction to the list of contributing forces that drive the self-assembly process. We first explored the self-assembly behavior of a set of ssDNA aptamer-amphiphiles composed of the same hydrophobic tail and hydrophilic ssDNA aptamer headgroup but with different spacer molecules linking these groups together. Through the use of cryo-transmission electron microscopy (cryo-TEM), small angle x-ray scattering (SAXS), and circular dichroism (CD) we show that the aptamer-amphiphiles can assemble into a variety of structures depending on the spacer used. We demonstrated, for the first time, the creation of self-assembled aptamer-amphiphile nanotape structures and show that the choice of the spacer used in the design of aptamer-amphiphiles can influence their supramolecular self-assembly as well as the secondary structure of the aptamer headgroup. We next explored the role of the ssDNA headgroup on the amphiphile self-assembly behavior by designing amphiphiles with headgroups of multiple lengths and nucleotides sequences. Amphiphiles of each headgroup length that contained hydrophobic spacers were found to assemble into twisted nanotapes, helical nanotapes and nanotubes as the nanotapes grew in width. In few instances, guanine-rich headgroups were capable of forming nanotape and nanotube structures in the absence of the hydrophobic spacer. Together, these studies demonstrate the ability of ssDNA-amphiphiles to form complex nanostructures that may be useful in a variety of DNA nanotechnology applications

Validation of computational models to characterize cumulative intake curves from video-coded meals

IntroductionObservational coding of eating behaviors (e.g., bites, eating rate) captures behavioral characteristics but is limited in its ability to capture dynamic patterns (e.g., temporal changes) across a meal. While the Universal Eating Monitor captures dynamic patterns of eating through cumulative intake curves, it is not commonly used in children due to strict behavioral protocols. Therefore, the objective of this study was to test the ability of computational models to characterize cumulative intake curves from video-coded meals without the use of continuous meal weight measurement.MethodsCumulative intake curves were estimated using Kisslieff’s Quadratic model and Thomas’s logistic ordinary differential equation (LODE) model. To test if cumulative intake curves could be characterized from video-coded meals, three different types of data were simulated: (1) Constant Bite: simplified cumulative intake data; (2) Variable Bite: continuously measured meal weight data; and (3) Bite Measurement Error: video-coded meals that require the use of average bite size rather than measured bite size.ResultsPerformance did not differ by condition, which was assessed by examining model parameter recovery, goodness of fit, and prediction error. Therefore, the additional error incurred by using average bite size as one would with video-coded meals did not impact the ability to accurately estimate cumulative intake curves. While the Quadratic and LODE models were comparable in their ability to characterize cumulative intake curves, the LODE model parameters were more distinct than the Quadradic model. Greater distinctness suggests the LODE model may be more sensitive to individual differences in cumulative intake curves.DiscussionCharacterizing cumulative intake curves from video-coded meals expands our ability to capture dynamic patterns of eating behaviors in populations that are less amenable to strict protocols such as children and individuals with disordered eating. This will improve our ability to identify patterns of eating behavior associated with overconsumption and provide new opportunities for treatment

A Chandra Study of the Effects of a Major Merger on the Structure of Abell 2319

We present an analysis of a Chandra observation of the massive, nearby galaxy cluster Abell 2319. A sharp surface brightness discontinuity--suggested by previous, lower angular resolution X-ray imaging--is clearly visible in the ACIS image. This roughly 300kpc feature suggests that a major merger is taking place with a significant velocity component perpendicular to the line of sight. The cluster emission-weighted mean temperature is 11.8+/-0.6kev, somewhat higher than previous temperature measurements. The Chandra temperature map of A2319 reveals substructure resembling that anticipated based on hydrodynamic simulations of cluster mergers. The merger feature shows a pressure change across the surface brightness discontinuity by a factor of <=2.5. The higher density side of the front has a lower temperature, suggesting the presence of a cold front similar to those in many other merging clusters. The velocity of the front is roughly sonic. We compare bulk properties of the ICM and galaxies in A2319 to the same properties in a large sample of clusters as a way of gauging the effects of the major merger. Interestingly, by comparing A2319 to a sample of 44 clusters studied with the ROSAT PSPC we find that the X-ray luminosity, isophotal size, and ICM mass are consistent with the expected values for a cluster of its temperature; in addition, the K-band galaxy light is consistent with the light--temperature scaling relation derived from a sample of about 100 clusters studied with 2MASS. Together, these results indicate either that the merger in A2319 has not been effective at altering the bulk properties of the cluster, or that there are large but correlated displacements in these quantities.Comment: 11 pages, 8 figures, ApJ Submitte

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Deploying chemosensor arrays in close proximity to stationary phases imposes stimulusdependent spatio-temporal dynamics on their response and leads to improvements in complex odour discrimination. These spatio-temporal dynamics need to be taken into account explicitly when considering the detection performance of this new odour sensing technology, termed an artificial olfactory mucosa. For this purpose, we develop here a new measure of spatio-temporal information that combined with an analytical model of the artificial mucosa, chemosensor and noise dynamics completely characterizes the discrimination capability of the system. This spatio-temporal information measure allows us to quantify the contribution of both space and time to discrimination performance and may be used as part of optimization studies or calculated directly from an artificial mucosa output. Our formal analysis shows that exploiting both space and time in the mucosa response always outperforms the use of space alone and is further demonstrated by comparing the spatial versus spatio-temporal information content of mucosa experimental data. Together, the combination of the spatio-temporal information measure and the analytical model can be applied to extract the general principles of the artificial mucosa design as well as to optimize the physical and operating parameters that determine discrimination performance

Long-term collaboration reaps dividends for clinical research in chronic movement disorders.

Poster presented at the Clinical Trials Symposium, RD&E Exeter, 5/11/15

Effects of Mergers and Core Structure on the Bulk Properties of Nearby Galaxy Clusters

We use morphological measurements and the scatter of clusters about observed and simulated scaling relations to examine the impact of merging and core-related phenomena on the structure of galaxy clusters. All relations constructed from emission-weighted mean temperature and intracluster medium mass, X-ray luminosity, isophotal size, or near-IR luminosity show a separation between cool core (CC) and non-cool core (NCC) clusters. We attribute this partially to a temperature bias in CC clusters, and partially to other cool core-related structural changes. We attempt to minimize CC/NCC separation in scaling relations by applying a uniform scale factor to CC cluster temperatures and determining the scale factor for each relation that minimizes the separation between CC and NCC populations, and by introducing central surface brightness as a third parameter in relations. The latter approach reduces scatter in relations more than temperature scaling. We compare the scatter within subsamples split by CC/NCC and morphological merger indicators. CC clusters and clusters with less substructure generally exhibit higher scatter about relations. The larger structural variations in CC clusters exit well outside the core, suggesting that a process more global than core radiative instability is at work. Simulations without cooling mechanisms also show no correlation between substructure and larger scatter about relations, indicating that any merger-related scatter increases are subtle. The results indicate that cool core related phenomena, not merging processes, are the primary contributor to scatter in scaling relations. Our analysis does not appear to support the scenario in which clusters evolve cool cores over time unless they experience major mergers. (Abridged)Comment: 18 pages, 17 figures; minor changes to text to match accepted version. To appear in Ap

Preventing species extinctions: A global conservation consortium for Erica

Societal Impact Statement Human-caused habitat destruction and transformation is resulting in a cascade of impacts to biological diversity, of which arguably the most fundamental is species extinctions. The Global Conservation Consortia (GCC) are a means to pool efforts and expertise across national boundaries and between disciplines in the attempt to prevent such losses in focal plant groups. GCC Erica coordinates an international response to extinction threats in one such group, the heaths, or heathers, of which hundreds of species are found only in South Africa's spectacularly diverse Cape Floristic Region. Summary Effectively combating the biodiversity crisis requires coordinated conservation efforts. Botanic Gardens Conservation International (BGCI) and numerous partners have established Global Conservation Consortia (GCC) to collaboratively develop and implement comprehensive conservation strategies for priority threatened plant groups. Through these networks, institutions with specialised collections and staff can leverage ongoing work to optimise impact for threatened plant species. The genus Erica poses a challenge similar in scale to that of the largest other GCC group, Rhododendron, but almost 700 of the around 800 known species of Erica are concentrated in a single biodiversity hotspot, the Cape Floristic Region (CFR) of South Africa. Many species are known to be threatened, suffering the immediate impacts of habitat destruction, invasive species, changes in natural fire regimes and climate change. Efforts to counter these threats face general challenges: disproportionate burden of in situ conservation falling on a minority of the community, limited knowledge of species-rich groups, shortfalls in assessing and monitoring threat, lack of resources for in situ and limitations of knowledge for ex situ conservation efforts and in communicating the value of biological diversity to a public who may never encounter it in the wild. GCC Erica brings together the world's Erica experts, conservationists and the botanical community, including botanic gardens, seed banks and organisations in Africa, Madagascar, Europe, the United States, Australia and beyond. We are collaboratively pooling our unique sets of skills and resources to address these challenges in working groups for conservation prioritisation, conservation in situ, horticulture, seed banking, systematic research and outreach.publishedVersio

Physiotherapy and occupational therapy vs no therapy in mild to moderate Parkinson disease: a randomized clinical trial

IMPORTANCE It is unclear whether physiotherapy and occupational therapy are clinically effective and cost-effective in Parkinson disease (PD). OBJECTIVE To perform a large pragmatic randomized clinical trial to evaluate the clinical effectiveness of individualized physiotherapy and occupational therapy in PD. DESIGN, SETTING, AND PARTICIPANTS The PD REHAB Trial was a multicenter, open-label, parallel group, controlled efficacy trial. A total of 762 patients with mild to moderate PD were recruited from 38 sites across the United Kingdom. Recruitment took place between October 2009 and June 2012, with 15 months of follow-up. INTERVENTIONS Participants with limitations in activities of daily living (ADL) were randomized to physiotherapy and occupational therapy or no therapy. MAIN OUTCOMES AND MEASURES The primary outcome was the Nottingham Extended Activities of Daily Living (NEADL) Scale score at 3 months after randomization. Secondary outcomes were health-related quality of life (assessed by Parkinson Disease Questionnaire–39 and EuroQol-5D); adverse events; and caregiver quality of life. Outcomes were assessed before trial entry and then 3, 9, and 15 months after randomization. RESULTS Of the 762 patients included in the study (mean [SD] age, 70 [9.1] years), 381 received physiotherapy and occupational therapy and 381 received no therapy. At 3 months, there was no difference between groups in NEADL total score (difference, 0.5 points; 95%CI, −0.7 to 1.7; P = .41) or Parkinson Disease Questionnaire–39 summary index (0.007 points; 95%CI, −1.5 to 1.5; P = .99). The EuroQol-5D quotient was of borderline significance in favor of therapy (−0.03; 95%CI, −0.07 to −0.002; P = .04). The median therapist contact time was 4 visits of 58 minutes over 8 weeks. Repeated-measures analysis showed no difference in NEADL total score, but Parkinson Disease Questionnaire–39 summary index (diverging 1.6 points per annum; 95%CI, 0.47 to 2.62; P = .005) and EuroQol-5D score (0.02; 95%CI, 0.00007 to 0.03; P = .04) showed small differences in favor of therapy. There was no difference in adverse events. CONCLUSIONS AND RELEVANCE Physiotherapy and occupational therapy were not associated with immediate or medium-term clinically meaningful improvements in ADL or quality of life in mild to moderate PD. This evidence does not support the use of low-dose, patient-centered, goal-directed physiotherapy and occupational therapy in patients in the early stages of PD. Future research should explore the development and testing of more structured and intensive physical and occupational therapy programs in patients with all stages of PD

Practical guidelines and recent advances in the Itrax XRF core-scanning procedure

XRF core scanning has evolved to become a standard analytical technique for the rapid assessment of elemental, density and textural variations in a wide range of sediments and other materials, with applications ranging from palaeoceanography, paleoclimatology, geology, and environmental forensics to environmental protection. In general, scanning provides rapid, non-destructive acquisition of elemental and textural variations at sub-millimetre resolution for a wide range of materials. Numerous procedural adaptations have been developed for the growing number of applications, such as analyses of unconsolidated, water-rich sediments, powdered soil samples, or resin bags. Here, practical expertise and guidance from the Itrax community, gained over 15 years, is presented that should provide insights for new and experienced users