F1 Rft 2012 Setups
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Label-free DNA nucleobase recognition by fluorescent small molecules has received much attention due to its simplicity in mutation identification and drug screening. However, sequence-dependent fluorescence light-up nucleobase recognition and multicolor emission with individual emission energy for individual nucleobases have been seldom realized. Herein, an abasic site (AP site) in a DNA duplex was employed as a binding field for berberine, one of isoquinoline alkaloids. Unlike weak binding of berberine to the fully matched DNAs without the AP site, strong binding of berberine to the AP site occurs and the berberine's fluorescence light-up behaviors are highly dependent on the target nucleobases opposite the AP site in which the targets thymine and cytosine produce dual emission bands, while the targets guanine and adenine only give a single emission band. Furthermore, more intense emissions are observed for the target pyrimidines than purines. The flanking bases of the AP site also produce some modifications of the berberine's emission behavior. The binding selectivity of berberine at the AP site is also confirmed by measurements of fluorescence resonance energy transfer, excited-state lifetime, DNA melting and fluorescence quenching by ferrocyanide and sodium chloride. It is expected that the target pyrimidines cause berberine to be stacked well within DNA base pairs near the AP site, which results in a strong resonance coupling of the electronic transitions to the particular vibration mode to produce the dual emissions. The fluorescent signal-on and emission energy-modulated sensing for nucleobases based on this fluorophore is substantially advantageous over the previously used fluorophores. We expect that this approach will be developed as a practical device for differentiating pyrimidines from purines by positioning an AP site toward a target that is available for readout by this alkaloid probe. This journal is © The Royal Society of Chemistry 2012
In-Situ Resource Utilization (ISRU) and lunar science share similar objectives with respect to analyzing and characterizing the physical, mineral, and volatile materials and resources at sites of robotic and human exploration. To help mature and stress instruments, technologies, and hardware and to evaluate operations and procedures, space agencies have utilized demonstrations at analog sites on Earth before use in future missions. The US National Aeronautics and Space Administration (NASA), the Canadian Space Agency (CSA), and the German Space Agency (DLR) have utilized an analog site on the slope of Mauna Kea on the Big Island of Hawaii to test ISRU and lunar science hardware and operations in two previously held analog field tests. NASA and CSA are currently planning on a 3rd analog field test to be held in June, 2012 in Hawaii that will expand upon the successes from the previous two field tests.
Our aim was to improve the in vivo pharmacokinetics and pharmacodynamics of exendin-4 by using site-specific PEGylation. We designed the PEGylated peptide based on its structure and activity relationship and prepared the conjugate by two steps of chromatographic purification. After obtained the conjugate we confirmed its glucose-lowering activity in normal mice and determined its half-life in SD rats. Then we evaluated its anti-diabetic activity in a multiple low-dose Streptozocin (STZ)-induced diabetic mice model. With the process established in this study the product conjugate was obtained with a yield of over 60% and purity of above 99%. The conjugate maintained its original conformation after modification. In SD rats its half-life was prolonged to 27.12 ± 5.75 h which was 17.61-fold longer than that of the natural exendin-4 for which the half-life was only 1.54 ± 0.47 h. Its anti-diabetic activity was significantly improved in the diabetic mice. Compare with native exendin-4, the C-terminal site-specific PEGylated analog of exendin-4 obtained in this study has an improved pharmacokinetics and pharmacodynamics in vivo and could be regarded as a potential candidate for the future development of anti-diabetic drugs. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.
Current commercial PCV2 vaccines are all based on PCV2a and have been shown to be effective in reducing PCV2a and PCV2b viremia and PCV2-associated lesions and disease. The recent emergence of novel mutant PCV2 (mPCV2) strains and linkage of mPCV2 with cases of porcine circovirus associated disease (PCVAD) in vaccinated herds have raised concerns over emergence of vaccine-escape mutants and reduced efficacy of PCV2a-based vaccines. The aim of this study was to determine the ability of three commercial PCV2a-based vaccines administered in the presence of an ongoing PCV2b infection and passively-acquired anti-PCV2 antibodies to protect conventional pigs against experimental challenge with mPCV2 at 11 weeks of age. Fifty naturally PCV2b-infected 2-week-old pigs were divided into five treatment groups with 10 pigs each. Pigs were unvaccinated (positive and negative controls) or vaccinated at 3 (VAC-A, VAC-B, VAC-C) and at 5 weeks of age (VAC-C). At 11 weeks of age, all pigs except the negative controls were challenged with a 2012 U.S. strain of mPCV2. The experiment was terminated 21 days after challenge. Under the conditions of this study, vaccinated pigs were protected against PCV2 viremia and lesions whereas non-vaccinated pigs were not. Moreover, concurrent PCV2b and mPCV2 infection was demonstrated in all positive controls and 3/10 had microscopic lesions consistent with PCVAD while negative controls infected with PCV2b alone did not develop PCVAD. The results indicate that concurrent PCV2b/mPCV2 infection can trigger PCVAD development and that commercial vaccines are effective in protecting conventional pigs against emerging mPCV2 strains. Copyright © 2014 Elsevier Ltd. All rights reserved.
Austrian Space Forum: The Austrian Space Forum (OeWF, Österreichisches Weltraum Forum) is a non-profit, citizen-science organization of aerospace specialists and enthusiasts. One of its specialisations is Mars analog research. Analog studies and analog instrument validation supported all planetary surface missions so far [1] and are considered as an effective tool to prepare for future missions to Mars [2,3,4,5,6,7]. Since 2006, OeWF has conducted 11 Mars analog field campaigns in diverse locations that represented: 1) average current Mars conditions (the Mars Desert Research Station (MDRS) in Utah in 2006 [8] and the Northern Sahara near Erfoud, Morocco in 2013 [9]); 2) the early and wet Mars (analog site of Rio Tinto Spain in 2011 [10]); and 3) subsurface exploration (Dachstein Ice Caves in 2012). During these campaigns, 68 experiments and major engineering tests were performed, whichwere mostly focused on astrobiology, robotics, human factors, geoscience and spacesuit operations. Major assets of OeWF include two advanced spacesuit simulators Aouda [11], an increasingly evolving Mission Support Center, a dedicated Remote Science Support team [12], and a growing set of Standard Operating Procedures defining major workflows within a mission team. The spacesuit simulators were operated by a total of 18 analog astronauts, who were selected and trained during a >6 month program. Total EVA time is nearly 600 hours, leading to a significant experience in analog field simulations. AMADEE-15: The mission took place between August 2nd and 14th 2015 at the Kaunertal Glacier in Tyrol, Austria. This glacier was selected as a study site because of its accessibility and high number of micro-landscapes analogous to those expected on Mars in locations where abundant water ice is present. As such it is considered a first-tier Mars analog [13]. The Base station was located at N 46.86320, E 10.71401 at 2800 masl, the highest reached location was on elevation of 2887 m. Eleven
Field testing and scientific investigations were conducted on the Mauna Kea Volcano, Hawaii, as part of the 2012 Moon and Mars Analog Mission Activities (MMAMA). Measurements were conducted using both stand-alone and rover-mounted instruments to determine the geophysical and geochemical properties of the field site, as well as provide operational constraints and science considerations for future robotic and human missions [1]. Reported here are the results from the two MIMOS instruments deployed as part of this planetary analog field test.
How can humans acquire relational representations that enable analogical inference and other forms of high-level reasoning? Using comparative relations as a model domain, we explore the possibility that bottom-up learning mechanisms applied to objects coded as feature vectors can yield representations of relations sufficient to solve analogy problems. We introduce Bayesian analogy with relational transformations (BART) and apply the model to the task of learning first-order comparative relations (e.g., larger, smaller, fiercer, meeker) from a set of animal pairs. Inputs are coded by vectors of continuous-valued features, based either on human magnitude ratings, normed feature ratings (De Deyne et al., 2008), or outputs of the topics model (Griffiths, Steyvers, & Tenenbaum, 2007). Bootstrapping from empirical priors, the model is able to induce first-order relations represented as probabilistic weight distributions, even when given positive examples only. These learned representations allow classification of novel instantiations of the relations and yield a symbolic distance effect of the sort obtained with both humans and other primates. BART then transforms its learned weight distributions by importance-guided mapping, thereby placing distinct dimensions into correspondence. These transformed representations allow BART to reliably solve 4-term analogies (e.g., larger:smaller::fiercer:meeker), a type of reasoning that is arguably specific to humans. Our results provide a proof-of-concept that structured analogies can be solved with representations induced from unstructured feature vectors by mechanisms that operate in a largely bottom-up fashion. We discuss potential implications for algorithmic and neural models of relational thinking, as well as for the evolution of abstract thought. Copyright 2012 APA, all rights reserved. 2b1af7f3a8