Factors to Consider in Improving Prescription Drug Pharmacy Leaflets

Today, when consumers receive prescription drug pharmacy leaflets (also known as ‘consumer medication information’ or CMI), they often appear in small font size, with cluttered layouts, and distracting information. This problem has attracted the attention of the U.S. Food and Drug Administration in advocating for more comprehendible, accurate, and easy-to-access CMI formats. Our study of four different CMI prototypes shows that an expanded Over-the-Counter (OTC) Drug Facts prototype is the best for improving comprehension accuracy, and is especially effective for those with lower health literacy and health motivation. A simpler OTC prototype did not aid accuracy scores due in part to its lack of complexity; whereas the most complex prototype (the revised medication guide – similar to most CMI today) reduced leaflet likability and usage intentions. Finally, continued leaflet availability improved accuracy scores for lower health literacy and health motivation respondents. Implications for marketing and public health policy are offered

Control of RelB during dendritic cell activation integrates canonical and noncanonical NF-κB pathways.

The NF-κB protein RelB controls dendritic cell (DC) maturation and may be targeted therapeutically to manipulate T cell responses in disease. Here we report that RelB promoted DC activation not as the expected RelB-p52 effector of the noncanonical NF-κB pathway, but as a RelB-p50 dimer regulated by canonical IκBs, IκBα and IκBɛ. IκB control of RelB minimized spontaneous maturation but enabled rapid pathogen-responsive maturation. Computational modeling of the NF-κB signaling module identified control points of this unexpected cell type-specific regulation. Fibroblasts that we engineered accordingly showed DC-like RelB control. Canonical pathway control of RelB regulated pathogen-responsive gene expression programs. This work illustrates the potential utility of systems analyses in guiding the development of combination therapeutics for modulating DC-dependent T cell responses

Coordinating Networked Learning Activities with a General-Purpose Interface

Classrooms equipped with wirelessly networked tablets and handhelds can engage students in powerful collaborative learning activities that are otherwise impractical or impossible. However, the system must fulfill certain technological and pedagogical requirements such as tolerance for latecomers, supporting disconnected mode gracefully, robustness across dropped connections, promotion of both positive interdependence and individual accountability, and accommodation of differential rates of task completion. Two approaches to making a Tuple Space-based computer architecture for connectivity into an inviting environment for the generation and creation of novel coordinated activities were attempted. One approach made the technological “bones” of the system very clear but assumed user vision of the complex goals and settings of real education. The more satisfactory approach made clear how Tuple Spaces matches the complex goals and settings of real education, but backgrounded technical complexity. This approach provides users with a system, Group Scribbles, which may inspire a wide range of uses.SRI International Virginia Tech Newport Universit

A novel lineage of proteobacteria involved in formation of marine Fe-oxidizing microbial mat communities

© The Authors, 2007. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in PLoS One 2 (2007): e667, doi:10.1371/journal.pone.0000667.For decades it has been recognized that neutrophilic Fe-oxidizing bacteria (FeOB) are associated with hydrothermal venting of Fe(II)-rich fluids associated with seamounts in the world's oceans. The evidence was based almost entirely on the mineralogical remains of the microbes, which themselves had neither been brought into culture or been assigned to a specific phylogenetic clade. We have used both cultivation and cultivation-independent techniques to study Fe-rich microbial mats associated with hydrothermal venting at Loihi Seamount, a submarine volcano. Using gradient enrichment techniques, two iron-oxidizing bacteria, strains PV-1 and JV-1, were isolated. Chemolithotrophic growth was observed under microaerobic conditions; Fe(II) and Fe0 were the only energy sources that supported growth. Both strains produced filamentous stalk-like structures composed of multiple nanometer sized fibrils of Fe-oxyhydroxide. These were consistent with mineralogical structures found in the iron mats. Phylogenetic analysis of the small subunit (SSU) rRNA gene demonstrated that strains PV-1 and JV-1 were identical and formed a monophyletic group deeply rooted within the Proteobacteria. The most similar sequence (85.3% similarity) from a cultivated isolate came from Methylophaga marina. Phylogenetic analysis of the RecA and GyrB protein sequences confirmed that these strains are distantly related to other members of the Proteobacteria. A cultivation-independent analysis of the SSU rRNA gene by terminal-restriction fragment (T-RF) profiling showed that this phylotype was most common in a variety of microbial mats collected at different times and locations at Loihi. On the basis of phylogenetic and physiological data, it is proposed that isolate PV-1T ( = 1ATCC BAA-1019: JCM 14766) represents the type strain of a novel species in a new genus, Mariprofundus ferrooxydans gen. nov., sp. nov. Furthermore, the strain is the first cultured representative of a new candidatus class of the Proteobacteria that is widely distributed in deep-sea environments, Candidatus ζ (zeta)-Proteobacteria cl. nov.Funding was provided to DE and CLM by the National Science Foundation (0348330) and to DE through the NASA Astobiology Institute

Constraining white-dwarf kicks in globular clusters : III. Cluster Heating

Recent observations of white dwarfs in globular clusters indicate that these stars may get a velocity kick during their time as giants. This velocity kick could originate naturally if the mass loss while on the asymptotic giant branch is slightly asymmetric. The kicks may be large enough to dramatically change the radial distribution of young white dwarfs, giving them larger energies than other stars in the cluster. As these energetic white dwarfs travel through the cluster they can impart their excess energy on the other stars in the cluster. This new heat source for globular clusters is expected to be largest during the clusters' youth.Comment: 4 pages, 1 figure (changes to reflect published version

Evolution of Bacterial Phosphoglycerate Mutases: Non-Homologous Isofunctional Enzymes Undergoing Gene Losses, Gains and Lateral Transfers

The glycolytic phosphoglycerate mutases exist as non-homologous isofunctional enzymes (NISE) having independent evolutionary origins and no similarity in primary sequence, 3D structure, or catalytic mechanism. Cofactor-dependent PGM (dPGM) requires 2,3-bisphosphoglycerate for activity; cofactor-independent PGM (iPGM) does not. The PGM profile of any given bacterium is unpredictable and some organisms such as Escherichia coli encode both forms.To examine the distribution of PGM NISE throughout the Bacteria, and gain insight into the evolutionary processes that shape their phyletic profiles, we searched bacterial genome sequences for the presence of dPGM and iPGM. Both forms exhibited patchy distributions throughout the bacterial domain. Species within the same genus, or even strains of the same species, frequently differ in their PGM repertoire. The distribution is further complicated by the common occurrence of dPGM paralogs, while iPGM paralogs are rare. Larger genomes are more likely to accommodate PGM paralogs or both NISE forms. Lateral gene transfers have shaped the PGM profiles with intradomain and interdomain transfers apparent. Archaeal-type iPGM was identified in many bacteria, often as the sole PGM. To address the function of PGM NISE in an organism encoding both forms, we analyzed recombinant enzymes from E. coli. Both NISE were active mutases, but the specific activity of dPGM greatly exceeded that of iPGM, which showed highest activity in the presence of manganese. We created PGM null mutants in E. coli and discovered the ΔdPGM mutant grew slowly due to a delay in exiting stationary phase. Overexpression of dPGM or iPGM overcame this defect.Our biochemical and genetic analyses in E. coli firmly establish dPGM and iPGM as NISE. Metabolic redundancy is indicated since only larger genomes encode both forms. Non-orthologous gene displacement can fully account for the non-uniform PGM distribution we report across the bacterial domain

Short-Term Immunosuppression Promotes Engraftment of Embryonic and Induced Pluripotent Stem Cells

SummaryEmbryonic stem cells (ESCs) are an attractive source for tissue regeneration and repair therapies because they can be differentiated into virtually any cell type in the adult body. However, for this approach to succeed, the transplanted ESCs must survive long enough to generate a therapeutic benefit. A major obstacle facing the engraftment of ESCs is transplant rejection by the immune system. Here we show that blocking leukocyte costimulatory molecules permits ESC engraftment. We demonstrate the success of this immunosuppressive therapy for mouse ESCs, human ESCs, mouse induced pluripotent stem cells (iPSCs), human induced pluripotent stem cells, and more differentiated ESC/(iPSCs) derivatives. Additionally, we provide evidence describing the mechanism by which inhibition of costimulatory molecules suppresses T cell activation. This report describes a short-term immunosuppressive approach capable of inducing engraftment of transplanted ESCs and iPSCs, providing a significant improvement in our mechanistic understanding of the critical role costimulatory molecules play in leukocyte activation

KinImmerse: Macromolecular VR for NMR ensembles

<p>Abstract</p> <p>Background</p> <p>In molecular applications, virtual reality (VR) and immersive virtual environments have generally been used and valued for the visual and interactive experience – to enhance intuition and communicate excitement – rather than as part of the actual research process. In contrast, this work develops a software infrastructure for research use and illustrates such use on a specific case.</p> <p>Methods</p> <p>The Syzygy open-source toolkit for VR software was used to write the KinImmerse program, which translates the molecular capabilities of the kinemage graphics format into software for display and manipulation in the DiVE (Duke immersive Virtual Environment) or other VR system. KinImmerse is supported by the flexible display construction and editing features in the KiNG kinemage viewer and it implements new forms of user interaction in the DiVE.</p> <p>Results</p> <p>In addition to molecular visualizations and navigation, KinImmerse provides a set of research tools for manipulation, identification, co-centering of multiple models, free-form 3D annotation, and output of results. The molecular research test case analyzes the local neighborhood around an individual atom within an ensemble of nuclear magnetic resonance (NMR) models, enabling immersive visual comparison of the local conformation with the local NMR experimental data, including target curves for residual dipolar couplings (RDCs).</p> <p>Conclusion</p> <p>The promise of KinImmerse for production-level molecular research in the DiVE is shown by the locally co-centered RDC visualization developed there, which gave new insights now being pursued in wider data analysis.</p

The Ellipticity and Orientation of Clusters of Galaxies from N-Body Experiments

In this study we use simulations of 128$^3$ particles to study the ellipticity and orientation of clusters of galaxies in N-body simulations of differing power-law initial spectra (P(k) \propto k^n ,n = +1, 0, -1, -2$), and density parameters ($\Omega_0 = 0.2$to 1.0). Furthermore, unlike most theoretical studies we mimic most observers by removing all particles which lie at distances greater than 2 1/h Mpc from the cluster center of mass. We computed the axial ratio and the principal axes using the inertia tensor of each cluster. The mean ellipticity of clusters increases strongly with increasing$n$. We also find that clusters tend to become more spherical at smaller radii. We compared the orientation of a cluster to the orientation of neighboring clusters as a function of distance (correlation). In addition, we considered whether a cluster's major axis tends to lie along the line connecting it to a neighboring cluster, as a function of distance (alignment). Both alignments and correlations were computed in three dimensions and in projection to mimic observational surveys. Our results show that significant alignments exist for all spectra at small separations ($D < 15 h^{-1}$Mpc) but drops off at larger distance in a strongly$n-$dependent way.Comment: 22 pages, requires aaspp4.sty, flushrt.sty, and epsf.sty Revised manuscript, accepted for publication in Ap

Parachute Models Used in the Mars Science Laboratory Entry, Descent, and Landing Simulation

An end-to-end simulation of the Mars Science Laboratory (MSL) entry, descent, and landing (EDL) sequence was created at the NASA Langley Research Center using the Program to Optimize Simulated Trajectories II (POST2). This simulation is capable of providing numerous MSL system and flight software responses, including Monte Carlo-derived statistics of these responses. The MSL POST2 simulation includes models of EDL system elements, including those related to the parachute system. Among these there are models for the parachute geometry, mass properties, deployment, inflation, opening force, area oscillations, aerodynamic coefficients, apparent mass, interaction with the main landing engines, and off-loading. These models were kept as simple as possible, considering the overall objectives of the simulation. The main purpose of this paper is to describe these parachute system models to the extent necessary to understand how they work and some of their limitations. A list of lessons learned during the development of the models and simulation is provided. Future improvements to the parachute system models are proposed