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Circadian rhythm sleep‐wake disorders (CRSWDs) are characterized by persistent or recurrent patterns of sleep disturbance related primarily to alterations of the circadian rhythm system or the misalignment between the endogenous circadian rhythm and exogenous factors that affect the timing or duration of sleep. These disorders collectively represent a significant unmet medical need, with a total prevalence in the millions, a substantial negative impact on quality of life, and a lack of studied treatments for most of these disorders. Activation of the endogenous melatonin receptors appears to play an important role in setting the circadian clock in the suprachiasmatic nucleus of the hypothalamus. Therefore, melatonin agonists, which may be able to shift and/or stabilize the circadian phase, have been identified as potential therapeutic candidates for the treatment of CRSWDs. Currently, only one melatonin receptor agonist, tasimelteon, is approved for the treatment of a CRSWD: non–24‐hour sleep‐wake disorder (or non‐24). However, three additional commercially available melatonin receptor agonists—agomelatine, prolonged‐release melatonin, and ramelteon—have been investigated for potential use for treatment of CRSWDs. Data indicate that these melatonin receptor agonists have distinct pharmacologic profiles that may help clarify their clinical use in CRSWDs. We review the pharmacokinetic and pharmacodynamic properties of these melatonin agonists and summarize their efficacy profiles when used for the treatment of CRSWDs. Further studies are needed to determine the therapeutic potential of these melatonin agonists for most CRSWDs.

As economic pressure and competition for budget among federal agencies has increased, there has been an increasing need for more granular data and robust management information systems. This is especially true for the execution of major civilian space programs. This need has resulted in new program management requirements being implemented in an attempt to limit cost and schedule growth. In particular, NASA Procedural Requirements (NPR) 7120.5D requires the implementation of an Earned Value Management System (EVMS) compliant with the requirements of American National Standards Institute (ANSI)/Electronic Industries Alliance Standard 748-B. The Radiation Belt Storm Probes (RBSP) program management team at The Johns Hopkins University Applied Physics Laboratory (JHU/APL) made a decision to implement an EVMS on RBSP during Phase B—a year earlier than specified in the contractual Phase C reporting requirement as defined in the NPR. This decision was made so that the project would have the benefit of 12 months of training and hands-on implementation during Phase B. Although there were a number of technical and process hurdles encountered during Phase B and into Phase C, the system was working well when the Integrated Baseline Review (IBR) was held in August 2009. The IBR was a success because it met the review requirements. It was also clear to all IBR participants that the EVMS was providing value to the project management team. Although the IBR pointed out some areas of concern regarding process and ANSI compliance, the system had markedly improved the project's ability to monitor cost and schedule. This, in turn, allowed the project team to foresee problems in advance, formulate corrective actions, and implement course corrections without causing significant adverse impact to the project. Opponents of EVMS systems often communicate the unfavorable opinion that EVMS systems create unnecessary cost and administration. Although it is undeniable that EVMS implementation does not occur without cost, the cost is minimal in comparison to the benefits of successful implementation. This paper will focus on the implementation of EVMS on the RBSP project, explain EV processes and the implementation's cost, and analyze the benefits of EVMS to provide insight into cost/benefit considerations for other projects considering EVMS implementation. This paper will do this by focusing on the following points: (1) RBSP is the first full-up implementation of earned value management (EVM) at JHU/APL; (2) RBSP EVM started in Phase B; (3) RBSP EVM implementation has been working well in Phase C/D; (4) RBSP EVM implementation has been recognized by Goddard Space Flight Center and NASA Headquarters as successful; and (5) an assessment of the benefits of EVMS to the project management team and sponsor shows that the system's benefits outweigh the cost of implementation.

This paper presents an objective and subjective verification of a high-resolution configuration of the Regional Atmospheric Modeling System (RAMS) over east-central Florida during the 1999 and 2000 summer months. Centered on the Cape Canaveral Air Force Station (CCAFS), the innermost nested grid of RAMS has a horizontal grid spacing of 1.25 km, thereby providing forecasts capable of modeling finescale phenomena such as ocean and river breezes, and convection. The RAMS is run operationally at CCAFS within the Eastern Range Dispersion Assessment System (ERDAS), in order to provide emergency response guidance during space operations. ERDAS uses RAMS wind and temperature fields for input into ERDAS diffusion algorithms; therefore, the accuracy of dispersion predictions is highly dependent on the accuracy of RAMS forecasts. The most substantial error in RAMS over east-central Florida is a surface-based cold temperature bias, primarily during the daylight hours. At the Shuttle Landing Facility, the RAMS point error statistics are not substantially different than the National Centers for Environment Prediction Eta Model; however, an objective evaluation consisting of only point error statistics cannot adequately determine the added value of a high-resolution model configuration. Thus, results from a subjective evaluation of the RAMS forecast sea breeze and thunderstorm initiation on the 1.25-km grid are also presented. According to the subjective verification of the Florida east coast sea breeze, the RAMS categorical and skill scores exceeded that of the Eta Model predictions in most instances. The RAMS skill scores in predicting thunderstorm initiation are much lower than the sea-breeze evaluation scores, likely resulting from the lack of a sophisticated data assimilation scheme in the current operational configuration.

The nucleus basalis (NB) has been implicated in memory formation indirectly, by lesions, pharmacological manipulations, and neural correlates of learning. Prior findings imply that engagement of the NB during learning promotes memory storage. We directly tested this NB-memory hypothesis by determining whether stimulation of the NB induces behavioral associative memory. Rats were trained either with paired tone (6 kHz) and NB stimulation or with the two stimuli unpaired. We later determined the specificity of cardiac and respiratory behavioral responses to the training tone and several other acoustic frequencies. Paired subjects exhibited frequency generalization gradients with a peak of 6 kHz for both cardiac and respiratory behavior. Unpaired subjects exhibited no generalization gradient. The development of such specific, associative behavioral responses indicates that tone paired with NB stimulation induced behavioral associative memory. The discovery of memory induction by direct activation of the NB supports the NB-memory hypothesis and provides a potentially powerful way to control and investigate neural mechanisms of memory.

The nucleus basalis (NB) mediates cortical electroencephalograph (EEG) activation; NB stimulation also modulates cortical responses to sensory stimuli and can induce learning-related receptive field plasticity. However, little is known about the behavioral effects of NB stimulation. This study concerns the effects of NB stimulation on cardiac and respiratory behavior and quantifies its EEG effects in freely moving rats. The EEG exhibited stimulation-induced decreases in theta and alpha power and increases in gamma power. NB stimulation elicited biphasic heart rate changes and disrupted ongoing respiration patterns. Neither EEG nor behavioral effects exhibited habituation or facilitation. These results indicate that the NB may serve not only as a cortical, but also as a behavioral, activation system that is normally engaged during learning.

Temporal relationships between adjacent single cells were studied in the auditory cortex of the waking guinea pig during silence and pure tone stimulation. One cell of each pair was responsive while the other was completely unresponsive Coordinated discharge was found for spontaneous activity in 14/17 (82%) pairs, generally at and near the origin of cross correlation histograms (CCHs, 5 ms bins). These relationships, involving the same temporal intervals, were also maintained during tone driven discharges of the responsive cell. Thus, responsive neurons may participate simultaneously in specific sensory processing tasks while also responding to a presumptive common modulatory influence within a local network, without the two processes necessarily being linked. Therefore, responsive cells may have greater information processing capacity than realized.