Model Averaging Software for Dichotomous Dose Response Risk Estimation

Model averaging has been shown to be a useful method for incorporating model uncertainty in quantitative risk estimation. In certain circumstances this technique is computationally complex, requiring sophisticated software to carry out the computation. We introduce software that implements model averaging for risk assessment based upon dichotomous dose-response data. This software, which we call Model Averaging for Dichotomous Response Benchmark Dose (MADr-BMD), fits the quantal response models, which are also used in the US Environmental Protection Agency benchmark dose software suite, and generates a model-averaged dose response model to generate benchmark dose and benchmark dose lower bound estimates. The software fulfills a need for risk assessors, allowing them to go beyond one single model in their risk assessments based on quantal data by focusing on a set of models that describes the experimental data.

Drug Predictive Cues Activate Aversion-Sensitive Striatal Neurons That Encode Drug Seeking

Drug-associated cues have profound effects on an addict’s emotional state and drug-seeking behavior. Although this influence must involve the motivational neural system that initiates and encodes the drug-seeking act, surprisingly little is known about the nature of such physiological events and their motivational consequences. Three experiments investigated the effect of a cocaine-predictive stimulus on dopamine signaling, neuronal activity, and reinstatement of cocaine seeking. In all experiments, rats were divided into two groups (paired and unpaired), and trained to self-administer cocaine in the presence of a tone that signaled the immediate availability of the drug. For rats in the paired group, self-administration sessions were preceded by a taste cue that signaled delayed drug availability. Assessments of hedonic responses indicated that this delay cue became aversive during training. Both the self-administration behavior and the immediate cue were subsequently extinguished in the absence of cocaine. After extinction of self-administration behavior, the presentation of the aversive delay cue reinstated drug seeking. In vivo electrophysiology and voltammetry recordings in the nucleus accumbens measured the neural responses to both the delay and immediate drug cues after extinction. Interestingly, the presentation of the delay cue simultaneously decreased dopamine signaling and increased excitatory encoding of the immediate cue. Most importantly, the delay cue selectively enhanced the baseline activity of neurons that would later encode drug seeking. Together these observations reveal how cocaine cues can modulate not only affective state, but also the neurochemical and downstream neurophysiological environment of striatal circuits in a manner that promotes drug seeking

Model Averaging Software for Dichotomous Dose Response Risk Estimation

Model averaging has been shown to be a useful method for incorporating model uncertainty in quantitative risk estimation. In certain circumstances this technique is computationally complex, requiring sophisticated software to carry out the computation. We introduce software that implements model averaging for risk assessment based upon dichotomous dose-response data. This software, which we call Model Averaging for Dichotomous Response Benchmark Dose (MADr-BMD), fits the quantal response models, which are also used in the US Environmental Protection Agency benchmark dose software suite, and generates a model-averaged dose response model to generate benchmark dose and benchmark dose lower bound estimates. The software fulfills a need for risk assessors, allowing them to go beyond one single model in their risk assessments based on quantal data by focusing on a set of models that describes the experimental data

Defects in cell spreading and ERK1/2 activation in fibroblasts with lamin A/C mutations

AbstractIn-frame mutations in nuclear lamin A/C lead to a multitude of tissue-specific degenerative diseases known as the ‘laminopathies’. Previous studies have demonstrated that lamin A/C-null mouse fibroblasts have defects in cell polarisation, suggesting a role for lamin A/C in nucleo-cytoskeletal-cell surface cross-talk. However, this has not been examined in patient fibroblasts expressing modified forms of lamin A/C. Here, we analysed skin fibroblasts from 3 patients with Emery–Dreifuss muscular dystrophy and from 1 with dilated cardiomyopathy. The emerin–lamin A/C interaction was impaired in each mutant cell line. Mutant cells exhibited enhanced cell proliferation, collagen-dependent adhesion, larger numbers of filopodia and smaller cell spread size, compared with control cells. Furthermore, cell migration, speed and polarization were elevated. Mutant cells also showed an enhanced ability to contract collagen gels at early time points, compared with control cells. Phosphotyrosine measurements during cell spreading indicated an initial temporal lag in ERK1/2 activation in our mutant cells, followed by hyper-activation of ERK1/2 at 2 h post cell attachment. Deregulated ERK1/2 activation is linked with cardiomyopathy, cell spreading and proliferation defects. We conclude that a functional emerin–lamin A/C complex is required for cell spreading and proliferation, possibly acting through ERK1/2 signalling

Ncera-101 Station Report from Kennedy Space Center, FL, USA (April 2017)

This is our annual report to the NCERA-101 meeting on the past year's activities related to controlled environment monitoring, operations and testing

Crossover Scaling in Dendritic Evolution at Low Undercooling

We examine scaling in two-dimensional simulations of dendritic growth at low undercooling, as well as in three-dimensional pivalic acid dendrites grown on NASA's USMP-4 Isothermal Dendritic Growth Experiment. We report new results on self-similar evolution in both the experiments and simulations. We find that the time dependent scaling of our low undercooling simulations displays a cross-over scaling from a regime different than that characterizing Laplacian growth to steady-state growth

New Frontiers in Food Production Beyond LEO

New technologies will be needed as mankind moves towards exploration of cislunar space, the Moon and Mars. Although many advances in our understanding of the effects of spaceflight on plant growth have been achieved in the last 40 years, spaceflight plant growth systems have been primarily designed to support space biology studies. Recently, the need for a sustainable and robust food system for future missions beyond Low Earth Orbit (LEO) has identified gaps in current technologies for food production. The goal is to develop safe and sustainable food production systems with reduced resupply mass and crew time compared to current systems

Value of Strain Imaging and Maximal Oxygen Consumption in Patients With Hypertrophic Cardiomyopathy

Longitudinal strain (LS) has been shown to be predictive of outcome in hypertrophic cardiomyopathy (HC). Percent predicted peak oxygen uptake (ppVO2), among other cardiopulmonary exercise testing (CPX) metrics, is a strong predictor of prognosis in HC. However, there has been limited investigation into the combination of LS and CPX metrics. This study sought to determine how LS and parameters of exercise performance contribute to prognosis in HC. One hundred and thirty-one consecutive patients with HC who underwent CPX and stress echocardiography were included. Global, septal, and lateral LS were assessed at rest and stress. Eighty matched individuals were used as controls. Patients were followed for the composite end point of death and worsening heart failure. All absolute LS components were lower in patients with HC than in controls (global 14.3\u2009\ub1\u20094.0% vs 18.8\u2009\ub1\u20092.2%, p 52\u2009ml/m2, and ppVO2 <80%. The combination of lateral LS, LAVI, and ppVO2 presents a simple model for outcome prediction

Comparative Study of Lettuce and Radish Grown Under Red and Blue LEDs and White Fluorescent Lamps

Growing vegetable crops in space will be an essential part of sustaining astronauts during long-range missions. To drive photosynthesis, red and blue light-emitting diodes (LEDs) have attracted attention because of their efficiency, longevity, small size, and safety. In efforts to optimize crop yield, there is also recent interest in analyzing the subtle effects of additional wavelengths on plant growth. For instance, since plants often look purplish gray under red and blue LEDs, the addition of green light allows easy recognition of disease and the assessment of plant health status. However, it is important to know if wavelengths outside the traditional red and blue wavebands have a direct effect on enhancing or hindering the mechanisms involved in plant growth. In this experiment, a comparative study was performed on two short cycle crops of red romaine lettuce (Lactuca sativa cv. "Outredgeous") and radish (Raphanus sativa cv. 'Cherry Bomb'), which were grown under two light treatments. The first treatment being red (630 nm) and blue (450 nm) LEDs alone, while the second treatment consisted of daylight tri-phosphor fluorescent lamps (CCT approximately 5000 K) at equal photosynthetic photon flux (PPF). The treatment effects were evaluated by measuring the fresh biomass produced, plant morphology and leaf dimensions, leaf chlorophyll content, and adenosine triphosphate (ATP) within plant leaf/storage root tissues