How tightly tuned are the synaptic and intrinsic properties that give rise to neuron and circuit function? Experimental work shows that these properties vary considerably across identified neurons in ...different animals. Given this variability in experimental data, this review describes some of the complications of building computational models to aid in understanding how system dynamics arise from the interaction of system components. We argue that instead of trying to build a single model that captures the generic behavior of a neuron or circuit, it is beneficial to construct a population of models that captures the behavior of the population that provided the experimental data. Studying a population of models with different underlying structure and similar behaviors provides opportunities to discover unsuspected compensatory mechanisms that contribute to neuron and network function.
This paper aimed at assessing the structural performance and sustainability of cold recycled asphalt pavements. Four cold recycling technologies were investigated, including the cold central-plant ...recycling with emulsified and foamed asphalt binders (i.e., CCPR-E and CCPR-F), and the cold in-place recycling with emulsified and foamed asphalt binders (i.e., CIR-E and CIR-F). Firstly, the laboratory tests were conducted to comprehensively evaluate the dynamic modulus, rutting, and cracking performance of cold recycled asphalt mixtures. Subsequently, these laboratory results were used to determine the inputs of cold recycled asphalt mixtures for the Pavement ME Design program, which was employed to predict the pavement performance. Meanwhile, the National Center for Asphalt Technology also constructed four cold recycled pavement sections in the field. The monitored and predicted pavement performance showed similar trends in the first two years, but the Pavement ME Design program over predicted the rut depth of these sections. The pavement performance results confirmed that the bottom-up fatigue cracking was a negligible distress mode for cold recycled asphalt pavements. In the following, the life cycle cost analysis and life cycle assessment were conducted to evaluate the four different cold recycling projects. The life cycle cost analysis results demonstrated that all of the four cold recycling projects yielded less net present values than the HMA project. The life cycle assessment data indicated that the cold recycling technologies reduced the energy consumption by 56–64%, and decreased the greenhouse gas emissions by 39–46%. Finally, this study found that the overlay and asphalt treated base thicknesses and climatic conditions had significant impact on the performance of cold recycled asphalt pavements.
Research in both animals and humans indicates that cannabidiol (CBD) has antipsychotic properties. The authors assessed the safety and effectiveness of CBD in patients with schizophrenia.
In an ...exploratory double-blind parallel-group trial, patients with schizophrenia were randomized in a 1:1 ratio to receive CBD (1000 mg/day; N=43) or placebo (N=45) alongside their existing antipsychotic medication. Participants were assessed before and after treatment using the Positive and Negative Syndrome Scale (PANSS), the Brief Assessment of Cognition in Schizophrenia (BACS), the Global Assessment of Functioning scale (GAF), and the improvement and severity scales of the Clinical Global Impressions Scale (CGI-I and CGI-S).
After 6 weeks of treatment, compared with the placebo group, the CBD group had lower levels of positive psychotic symptoms (PANSS: treatment difference=-1.4, 95% CI=-2.5, -0.2) and were more likely to have been rated as improved (CGI-I: treatment difference=-0.5, 95% CI=-0.8, -0.1) and as not severely unwell (CGI-S: treatment difference=-0.3, 95% CI=-0.5, 0.0) by the treating clinician. Patients who received CBD also showed greater improvements that fell short of statistical significance in cognitive performance (BACS: treatment difference=1.31, 95% CI=-0.10, 2.72) and in overall functioning (GAF: treatment difference=3.0, 95% CI=-0.4, 6.4). CBD was well tolerated, and rates of adverse events were similar between the CBD and placebo groups.
These findings suggest that CBD has beneficial effects in patients with schizophrenia. As CBD's effects do not appear to depend on dopamine receptor antagonism, this agent may represent a new class of treatment for the disorder.
The crab Cancer borealis undergoes large daily fluctuations in environmental temperature (8-24°C) and must maintain appropriate neural function in the face of this perturbation. In the pyloric ...circuit of the crab stomatogastric ganglion, we pharmacologically isolated the pacemaker kernel (the AB and PD neurons) and characterized its behavior in response to temperature ramps from 7°C to 31°C. For moderate temperatures, the pacemaker displayed a frequency-temperature curve statistically indistinguishable from that of the intact circuit, and like the intact circuit maintained a constant duty cycle. At high temperatures (above 23°C), a variety of different behaviors were seen: in some preparations the pacemaker increased in frequency, in some it slowed, and in many preparations the pacemaker stopped oscillating ("crashed"). Furthermore, these crashes seemed to fall into two qualitatively different classes. Additionally, the animal-to-animal variability in frequency increased at high temperatures. We used a series of Morris-Lecar mathematical models to gain insight into these phenomena. The biophysical components of the final model have temperature sensitivities similar to those found in nature, and can crash via two qualitatively different mechanisms that resemble those observed experimentally. The crash type is determined by the precise parameters of the model at the reference temperature, 11°C, which could explain why some preparations seem to crash in one way and some in another. Furthermore, even models with very similar behavior at the reference temperature diverge greatly at high temperatures, resembling the experimental observations.
Corrosion of stainless steels, including the austenitic Fe-Cr-Ni alloys, is associated with MnS inclusions that provide local sites for corrosion pits. Much research effort has been focused on the ...role of MnS in corrosion of conventional (cast and wrought) stainless steel to date, including microanalysis of MnS and the surrounding microchemistry. Herein, it was elucidated that an austenitic stainless steel (type 316L) when manufactured through selective laser melting was able to be produced without MnS inclusions and hence with no accompanying Cr-depletion in the vicinity of MnS, resulting in superior corrosion resistance relative to wrought form.
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We comprehensively review the current state-of-the-art of environmental monitoring for hydrophobic organic contaminants in aqueous matrices using passive sampling devices. Principles of the theory of ...passive sampling are presented. Strategies for passive sampler design and operation, limitations in performance and data quality-assurance and quality-control are reviewed. Advances in applications of available passive sampling devices are extensively critiqued. Future trends and current challenges facing practitioners and barriers to further adoption of the devices are discussed.
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Biologic scaffolds are derived from mammalian tissues, which must be decellularized to remove cellular antigens that would otherwise incite an adverse immune response. Although widely ...used clinically, the optimum balance between cell removal and the disruption of matrix architecture and surface ligand landscape remains a considerable challenge. Here we describe the use of time of flight secondary ion mass spectroscopy (ToF-SIMS) to provide sensitive, molecular specific, localized analysis of detergent decellularized biologic scaffolds. We detected residual detergent fragments, specifically from Triton X-100, sodium deoxycholate and sodium dodecyl sulphate (SDS) in decellularized scaffolds; increased SDS concentrations from 0.1% to 1.0% increased both the intensity of SDS fragments and adverse cell outcomes. We also identified cellular remnants, by detecting phosphate and phosphocholine ions in PAA and CHAPS decellularized scaffolds. The present study demonstrates ToF-SIMS is not only a powerful tool for characterization of biologic scaffold surface molecular functionality, but also enables sensitive assessment of decellularization efficacy.
We report here on the use of a highly sensitive analytical technique, time of flight secondary ion mass spectroscopy (ToF-SIMS) to characterize detergent decellularized scaffolds. ToF-SIMS detected cellular remnants and residual detergent fragments; increased intensity of the detergent fragments correlated with adverse cell matrix interactions. This study demonstrates the importance of maintaining a balance between cell removal and detergent disruption of matrix architecture and matrix surface ligand landscape. This study also demonstrates the power of ToF-SIMS for the characterization of decellularized scaffolds and capability for assessment of decellularization efficacy. Future use of biologic scaffolds in clinical tissue reconstruction will benefit from the fundamental results described in this work.
•A fully automated system to track multiple animals in a large arena without losing their identities is presented.•The system learns unique bleach patterns on the mice's fur and tracks them during ...both dark and light cycles.•Identification of six mice in the experimental setup was 97% correct during non-sleep intervals.•As a proof of principle, we tracked groups of four mice and report social trends that develop across hours and days.
A quantitative description of animal social behaviour is informative for behavioural biologists and clinicians developing drugs to treat social disorders. Social interaction in a group of animals has been difficult to measure because behaviour develops over long periods of time and requires tedious manual scoring, which is subjective and often non-reproducible. Computer-vision systems with the ability to measure complex social behaviour automatically would have a transformative impact on biology. Here, we present a method for tracking group-housed mice individually as they freely interact over multiple days. Each mouse is bleach-marked with a unique fur pattern. The patterns are automatically learned by the tracking software and used to infer identities. Trajectories are analysed to measure behaviour as it develops over days, beyond the range of acute experiments. We demonstrate how our system may be used to study the development of place preferences, associations and social relationships by tracking four mice continuously for five days. Our system enables accurate and reproducible characterisation of wild-type mouse social behaviour and paves the way for high-throughput long-term observation of the effects of genetic, pharmacological and environmental manipulations.
Requirements for explosive safety are often given in terms of a “K-Factor”, correlating incident blast effects with the distance and TNT equivalent weight of an explosion. Traditionally, this is ...conducted using empirical correlations to experimental measurements (e.g., the Kingery–Bulmash equations). In the far-field, empirical verification of incident overpressure and impulse magnitudes can be difficult; extrapolations from data give expected values at reasonable standoff distances that sometimes are too small to measure on available equipment but are larger than some regulations require. The present paper describes the results of numerical hydrocode analysis to verify the expected incident overpressure and impulse from small hemispherical ground charges of TNT at these relatively large distances. Furthermore, the dynamic effect of incident blast waves on lightweight, modular mitigation barriers is studied to gauge their effectiveness at providing safety standard compliance.
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