Deep Space Network information system architecture study

The purpose of this article is to describe an architecture for the Deep Space Network (DSN) information system in the years 2000-2010 and to provide guidelines for its evolution during the 1990s. The study scope is defined to be from the front-end areas at the antennas to the end users (spacecraft teams, principal investigators, archival storage systems, and non-NASA partners). The architectural vision provides guidance for major DSN implementation efforts during the next decade. A strong motivation for the study is an expected dramatic improvement in information-systems technologies, such as the following: computer processing, automation technology (including knowledge-based systems), networking and data transport, software and hardware engineering, and human-interface technology. The proposed Ground Information System has the following major features: unified architecture from the front-end area to the end user; open-systems standards to achieve interoperability; DSN production of level 0 data; delivery of level 0 data from the Deep Space Communications Complex, if desired; dedicated telemetry processors for each receiver; security against unauthorized access and errors; and highly automated monitor and control

Atomic Scale Structure and Chemical Composition across Order-Disorder Interfaces

Through a combination of aberration-corrected high-resolution scanning transmission electron microscopy and three-dimensional atom probe tomography, the true atomic-scale structure and change in chemical composition across the complex order-disorder interface in a metallic alloy has been determined. The study reveals the presence of two interfacial widths, one corresponding to an order-disorder transition, and the other to the compositional transition across the interface, raising fundamental questions regarding the definition of the interfacial width in such systems

Immunogenicity, Safety, and Efficacy of a Standalone Universal Influenza Vaccine, FLU-v, in Healthy Adults

Background: FLU-v is a broad-spectrum influenza vaccine that induces antibodies and cell-mediated immunity. Objective: To compare the safety, immunogenicity, and exploratory efficacy of different formulations and dosing regimens of FLU-v versus placebo. Design: Randomized, double-blind, placebo-controlled, single-center phase 2b clinical trial. (ClinicalTrials.gov: NCT02962908; Eudra CT: 2015-001932-38) Setting: The Netherlands. Participants: 175 healthy adults aged 18 to 60 years. Intervention: 0.5-mL subcutaneous injection of 500 mu g of adjuvanted (1 dose) or nonadjuvanted (2 doses) FLU-v (A-FLU-v or NA-FLU-v) or adjuvanted or nonadjuvanted placebo (A-placebo or NA-placebo) (2:2:1:1 ratio). Measurements: Vaccine-specific cellular responses at days 0, 42, and 180 were assessed via flow cytometry and enzyme-linked immunosorbent assay. Solicited information on adverse events (AEs) was collected for 21 days after vaccination. Unsolicited information on AEs was collected throughout the study. Results: The AEs with the highest incidence were mild to moderate injection site reactions. The difference between A-FLU-v and A-placebo in the median fold increase in secreted interferon-gamma (IFN-gamma) was 38.2-fold (95% CI, 4.7- to 69.7-fold; P = 0.001) at day 42 and 25.0-fold (CI, 5.7- to 50.9-fold; P <0.001) at day 180. The differences between A-FLU-v and A-placebo in median fold increase at day 42 were 4.5-fold (CI, 2.3- to 9.8-fold; P <0.001) for IFN-gamma-producing CD4+ T cells, 4.9-fold (CI, 1.3- to 40.0-fold; P <0.001) for tumor necrosis factor-alpha (TNF-alpha), 7.0-fold (CI, 3.5- to 18.0-fold; P <0.001) for interleukin-2 (IL-2), and 1.7-fold (CI, 0.1- to 4.0-fold; P = 0.004) for CD107a. At day 180, differences were 2.1-fold (CI, 0.0- to 6.0-fold; P = 0.030) for IFN-gamma and 5.7-fold (CI, 2.0- to 15.0-fold; P <0.001) for IL-2, with no difference for TNF-alpha or CD107a. No differences were seen between NA-FLU-v and NA-placebo. Limitation: The study was not powered to evaluate vaccine efficacy against influenza infection. Conclusion: Adjuvanted FLU-v is immunogenic and merits phase 3 development to explore efficacy. Primary Funding Source: SEEK and the European Commission Directorate-General for Research and Innovation, European Member States within the UNISEC (Universal Influenza Vaccines Secured) project

Fluticasone/formoterol combination therapy is as effective as fluticasone/salmeterol in the treatment of asthma, but has a more rapid onset of action: an open-label, randomized study

<p>Abstract</p> <p>Background</p> <p>The inhaled corticosteroid (ICS) fluticasone propionate (fluticasone) and the long-acting β₂-agonist (LABA) formoterol fumarate (formoterol) are being made available as a combination product (fluticasone/formoterol, <b><it>flutiform</it></b>^®) in a single aerosol inhaler. This 12-week, open-label, randomized, active-controlled, parallel-group, multicentre, phase 3 study compared the efficacy and safety of fluticasone/formoterol with the commercially available combination product fluticasone/salmeterol.</p> <p>Methods</p> <p>Patients aged ≥ 18 years (N = 202) with mild-to-moderate–severe, persistent asthma for ≥ 6 months prior to screening were included in the study. After a screening phase (4–10 days), eligible patients were randomized 1:1 to receive fluticasone/formoterol or fluticasone/salmeterol during the 12-week treatment period. The primary objective was to demonstrate non-inferiority of fluticasone/formoterol versus fluticasone/salmeterol, measured by pre-dose forced expiratory volume in the first second (FEV₁), at week 12.</p> <p>Results</p> <p>Fluticasone/formoterol was comparable to fluticasone/salmeterol for the primary efficacy endpoint, mean pre-dose FEV₁at week 12. The new combination was also comparable to fluticasone/salmeterol for change from baseline to week 12 in pre-dose FEV₁, change from pre-dose FEV₁at baseline to 2-hour post-dose FEV₁at week 12 and discontinuations due to lack of efficacy. Importantly, fluticasone/formoterol was superior to fluticasone/salmeterol in time to onset of action throughout the duration of the study. The two treatments demonstrated similar results for various other secondary efficacy parameters, including other lung function tests, patient-reported outcomes, rescue medication use, asthma exacerbations and Asthma Quality of Life Questionnaire scores. Fluticasone/formoterol was well tolerated and had a good safety profile that was similar to fluticasone/salmeterol.</p> <p>Conclusions</p> <p>The results of this study indicate that fluticasone/formoterol is as effective as fluticasone/salmeterol, and has a more rapid onset of action, reflecting the faster bronchodilatory effects of formoterol compared with those of salmeterol. If patients perceive the benefits of therapy with fluticasone/formoterol more rapidly than with fluticasone/salmeterol, this could have a positive impact on preference and adherence.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00476073">NCT00476073</a></p

Dendrimers in Nanoscale Confinement: The Interplay between Conformational Change and Nanopore Entrance

Hyperbranched dendrimers are nanocarriers for drugs, imaging agents, and catalysts. Their nanoscale confinement is of fundamental interest and occurs when dendrimers with bioactive payload block or pass biological nanochannels or when catalysts are entrapped in inorganic nanoporous support scaffolds. The molecular process of confinement and its effect on dendrimer conformations are, however, poorly understood. Here, we use single-molecule nanopore measurements and molecular dynamics simulations to establish an atomically detailed model of pore dendrimer interactions. We discover and explain that electrophoretic migration of polycationic PAMAM dendrimers into confined space is not dictated by the diameter of the branched molecules but by their size and generation-dependent compressibility. Differences in structural flexibility also rationalize the apparent anomaly that the experimental nanopore current read-out depends in nonlinear fashion on dendrimer size. Nanoscale confinement is inferred to reduce the protonation of the polycationic structures. Our model can likely be expanded to other dendrimers and be applied to improve the analysis of biophysical experiments, rationally design functional materials such as nanoporous filtration devices or nanoscale drug carriers that effectively pass biological pores

How Awareness Changes the Relative Weights of Evidence During Human Decision-Making

A combined behavioral and brain imaging study shows how sensory awareness and stimulus visibility can influence the dynamics of decision-making in humans

Bilayer-spanning DNA nanopores with voltage-switching between open and closed state.

Membrane-spanning nanopores from folded DNA are a recent example of biomimetic man-made nanostructures that can open up applications in biosensing, drug delivery, and nanofluidics. In this report, we generate a DNA nanopore based on the archetypal six-helix-bundle architecture and systematically characterize it via single-channel current recordings to address several fundamental scientific questions in this emerging field. We establish that the DNA pores exhibit two voltage-dependent conductance states. Low transmembrane voltages favor a stable high-conductance level, which corresponds to an unobstructed DNA pore. The expected inner width of the open channel is confirmed by measuring the conductance change as a function of poly(ethylene glycol) (PEG) size, whereby smaller PEGs are assumed to enter the pore. PEG sizing also clarifies that the main ion-conducting path runs through the membrane-spanning channel lumen as opposed to any proposed gap between the outer pore wall and the lipid bilayer. At higher voltages, the channel shows a main low-conductance state probably caused by electric-field-induced changes of the DNA pore in its conformation or orientation. This voltage-dependent switching between the open and closed states is observed with planar lipid bilayers as well as bilayers mounted on glass nanopipettes. These findings settle a discrepancy between two previously published conductances. By systematically exploring a large space of parameters and answering key questions, our report supports the development of DNA nanopores for nanobiotechnology.The SH lab is supported by the Leverhulme Trust (RPG-170), UCL Chemistry, EPSRC (Institutional Sponsorship Award), the National Physical Laboratory, and Oxford Nanopore Technologies. KG acknowledges funding from the Winton Program of Physics for Sustainability, Gates Cambridge and the Oppenheimer Trust. UFK was supported by an ERC starting grant #261101.This is the final version of the article. It was first published by ACS under the ACS AuthorChoice license at http://dx.doi.org/10.1021/nn5039433 This permits copying and redistribution of the article or any adaptations for non-commercial purposes

Degradation of aflatoxin B1 from naturally contaminated maize using the edible fungus Pleurotus ostreatus

Aflatoxins are highly carcinogenic secondary metabolites that can contaminate approximately 25% of crops and that cause or exacerbate multiple adverse health conditions, especially in Sub-Saharan Africa and South and Southeast Asia. Regulation and decontamination of aflatoxins in high exposure areas is lacking. Biological detoxification methods are promising because they are assumed to be cheaper and more environmentally friendly compared to chemical alternatives. White-rot fungi produce non-specific enzymes that are known to degrade aflatoxin in in situ and ex situ experiments. The aims of this study were to (1) decontaminate aflatoxin-B-1-(AFB(1)) in naturally contaminated maize with the edible, white-rot fungus Pleurotus ostreatus (oyster mushroom) using a solid-state fermentation system that followed standard cultivation techniques, and to (2) and to assess the risk of mutagenicity in the resulting breakdown products and mushrooms. Vegetative growth and yield characteristics of P. ostreatus were not inhibited by the presence of-AFB(1).-AFB(1) was degraded by up to 94% by the Blue strain. No aflatoxin could be detected in P. ostreatus mushrooms produced from-AFB(1)-contaminated maize. Moreover, the mutagenicity of breakdown products from the maize substrate, and reversion of breakdown products to the parent compound, were minimal. These results suggest that P. ostreatus significantly degrades-AFB(1) in naturally contaminated maize under standard cultivation techniques to levels that are acceptable for some livestock fodder, and that using P. ostreatus to bioconvert crops into mushrooms can reduce-AFB(1)-related losses.University of Arizona Green Fund [GF 15.31]Open Access Journal.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]