Remodelling of the natural product fumagillol employing a reaction discovery approach

In the search for new biologically active molecules, diversity-oriented synthetic strategies break through the limitation of traditional library synthesis by sampling new chemical space. Many natural products can be regarded as intriguing starting points for diversity-oriented synthesis, wherein stereochemically rich core structures may be reorganized into chemotypes that are distinctly different from the parent structure. Ideally, to be suited to library applications, such transformations should be general and involve few steps. With this objective in mind, the highly oxygenated natural product fumagillol has been successfully remodelled in several ways using a reaction-discovery-based approach. In reactions with amines, excellent regiocontrol in a bis-epoxide opening/cyclization sequence can be obtained by size-dependent interaction of an appropriate catalyst with the parent molecule, forming either perhydroisoindole or perhydroisoquinoline products. Perhydroisoindoles can be further remodelled by cascade processes to afford either morpholinone or bridged 4,1-benzoxazepine-containing structures.P50 GM067041 - NIGMS NIH HHS; P50 GM067041-07 - NIGMS NIH HHS; P50 GM067041-08 - NIGMS NIH HHS; P50 GM067041-09 - NIGMS NIH HH

Gas Brooder Maintenance.

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The positional-specificity effect reveals a passive-trace contribution to visual short-term memory.

The positional-specificity effect refers to enhanced performance in visual short-term memory (VSTM) when the recognition probe is presented at the same location as had been the sample, even though location is irrelevant to the match/nonmatch decision. We investigated the mechanisms underlying this effect with behavioral and fMRI studies of object change-detection performance. To test whether the positional-specificity effect is a direct consequence of active storage in VSTM, we varied memory load, reasoning that it should be observed for all objects presented in a sub-span array of items. The results, however, indicated that although robust with a memory load of 1, the positional-specificity effect was restricted to the second of two sequentially presented sample stimuli in a load-of-2 experiment. An additional behavioral experiment showed that this disruption wasn't due to the increased load per se, because actively processing a second object--in the absence of a storage requirement--also eliminated the effect. These behavioral findings suggest that, during tests of object memory, position-related information is not actively stored in VSTM, but may be retained in a passive tag that marks the most recent site of selection. The fMRI data were consistent with this interpretation, failing to find location-specific bias in sustained delay-period activity, but revealing an enhanced response to recognition probes that matched the location of that trial's sample stimulus

Genetic structure of community acquired methicillin-resistant Staphylococcus aureus USA300.

BackgroundCommunity-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is a significant bacterial pathogen that poses considerable clinical and public health challenges. The majority of the CA-MRSA disease burden consists of skin and soft tissue infections (SSTI) not associated with significant morbidity; however, CA-MRSA also causes severe, invasive infections resulting in significant morbidity and mortality. The broad range of disease severity may be influenced by bacterial genetic variation.ResultsWe sequenced the complete genomes of 36 CA-MRSA clinical isolates from the predominant North American community acquired clonal type USA300 (18 SSTI and 18 severe infection-associated isolates). While all 36 isolates shared remarkable genetic similarity, we found greater overall time-dependent sequence diversity among SSTI isolates. In addition, pathway analysis of non-synonymous variations revealed increased sequence diversity in the putative virulence genes of SSTI isolates.ConclusionsHere we report the first whole genome survey of diverse clinical isolates of the USA300 lineage and describe the evolution of the pathogen over time within a defined geographic area. The results demonstrate the close relatedness of clinically independent CA-MRSA isolates, which carry implications for understanding CA-MRSA epidemiology and combating its spread

Nimbus-7 ERB Solar Analysis Tape (ESAT) user's guide

Seven years and five months of Nimbus-7 Earth Radiation Budget (ERB) solar data are available on a single ERB Solar Analysis Tape (ESAT). The period covered is November 16, 1978 through March 31, 1986. The Nimbus-7 satellite performs approximately 14 orbits per day and the ERB solar telescope observes the sun once per orbit as the satellite crosses the southern terminator. The solar data were carefully calibrated and screened. Orbital and daily mean values are given for the total solar irradiance plus other spectral intervals (10 solar channels in all). In addition, selected solar activity indicators are included on the ESAT. The ESAT User's Guide is an update of the previous ESAT User's Guide (NASA TM 86143) and includes more detailed information on the solar data calibration, screening procedures, updated solar data plots, and applications to solar variability. Details of the tape format, including source code to access ESAT, are included

Optical/UV-to-X-Ray Echoes from the Tidal Disruption Flare ASASSN-14li

We carried out the first multi-wavelength (optical/UV and X-ray) photometric reverberation mapping of a tidal disruption flare (TDF) ASASSN-14li. We find that its X-ray variations are correlated with and lag the optical/UV fluctuations by 32$\pm$4 days. Based on the direction and the magnitude of the X-ray time lag, we rule out X-ray reprocessing and direct emission from a standard circular thin disk as the dominant source of its optical/UV emission. The lag magnitude also rules out an AGN disk-driven instability as the origin of ASASSN-14li and thus strongly supports the tidal disruption picture for this event and similar objects. We suggest that the majority of the optical/UV emission likely originates from debris stream self-interactions. Perturbations at the self-interaction sites produce optical/UV variability and travel down to the black hole where they modulate the X-rays. The time lag between the optical/UV and the X-rays variations thus correspond to the time taken by these fluctuations to travel from the self-interaction site to close to the black hole. We further discuss these time lags within the context of the three variants of the self-interaction model. High-cadence monitoring observations of future TDFs will be sensitive enough to detect these echoes and would allow us to establish the origin of optical/UV emission in TDFs in general.Comment: Publish in ApJ Letter

Analysis and use of VAS satellite data

A series of interrelated investigations has examined the analysis and use of VAS (VISSR Atmospheric Sounder) satellite data. A case study of VAS-derived mesoscale stability parameters suggested that they would have been a useful supplement to conventional data in the forecasting of thunderstorms on the day of interest. However, the meteorological significance of small or short lived stability features was uncertain. A second investigation examined the roles of first guess and VAS radiometric data in producing sounding retrievals. The radiance data often did not have a decisive influence on the final satellite soundings. Broad-scale patterns of the first guess, radiances, and retrievals frequently were similar, whereas small scale retrieval features, especially in the dew points, were often of uncertain origin

Implementation of an Adaptive Controller System from Concept to Flight Test

The National Aeronautics and Space Administration Dryden Flight Research Center (Edwards, California) is conducting ongoing flight research using adaptive controller algorithms. A highly modified McDonnell-Douglas NF-15B airplane called the F-15 Intelligent Flight Control System (IFCS) was used for these algorithms. This airplane has been modified by the addition of canards and by changing the flight control systems to interface a single-string research controller processor for neural network algorithms. Research goals included demonstration of revolutionary control approaches that can efficiently optimize aircraft performance for both normal and failure conditions, and to advance neural-network-based flight control technology for new aerospace systems designs. Before the NF-15B IFCS airplane was certified for flight test, however, certain processes needed to be completed. This paper presents an overview of these processes, including a description of the initial adaptive controller concepts followed by a discussion of modeling formulation and performance testing. Upon design finalization, the next steps are: integration with the system interfaces, verification of the software, validation of the hardware to the requirements, design of failure detection, development of safety limiters to minimize the effect of erroneous neural network commands, and creation of flight test control room displays to maximize human situational awareness