Safety Analysis of Signal-Coordinated Arterials with Multiple Heterogeneities

In the corresponding research available, the safety impact remains controversial in implementing signal coordination on arterials, which calls for an in-depth exploration with the appropriate statistical methods. Based on the traffic data from Ann Arbor City (Michigan, USA), the paper proposes a safety evaluation model considering the multiple heterogeneities. In terms of arterials with the coordinated signalization, modeling results imply that (1) the multivariate heterogeneity shows the strongest interaction on crash frequency, followed by the spatiotemporal and structural heterogeneities, and (2) the spatial variation is unrelated to the temporal change among crashes in the denoted traffic analysis zones (TAZs). In an attempt to alleviate the coupled crash risks along the coordinated arterials, the study emphasizes the necessity of dividing the subcontrol traffic areas in real time according to the correlative degree of crash distribution. Meanwhile, the modeling framework with multiple heterogeneities can be applied for the safety analysis of other urban roads.

Dominant role of adult neurogenesis-induced structural heterogeneities in driving plasticity heterogeneity in dentate gyrus granule cells

ABSTRACTNeurons and synapses manifest pronounced variability in the amount of plasticity induced by identical activity patterns. The mechanisms underlying such plasticity heterogeneity, implicated in context-specific resource allocation during encoding, have remained unexplored. Here, we employed a systematic, unbiased, and physiologically constrained search to identify the mechanisms behind plasticity heterogeneity in dentate gyrus granule cells. We found that each of intrinsic, synaptic, and structural heterogeneities independently yielded heterogeneous plasticity profiles obtained with two different induction protocols. However, prior predictions about strong relationships between neuronal intrinsic excitability and plasticity emerged only when adult-neurogenesis-induced structural heterogeneities were accounted for. Strikingly, despite the concomitant expression of heterogeneities in structural, synaptic, and intrinsic neuronal properties, similar plasticity profiles were attainable through synergistic interactions among these heterogeneities. Importantly, consequent to strong relationships with intrinsic excitability measurements, we found that synaptic plasticity in the physiological range was achieved in immature cells despite their electrophysiologically-observed weak synaptic strengths. Together, our analyses unveil the dominance of neurogenesis-induced structural heterogeneities in driving plasticity heterogeneity in granule cells. Broadly, these analyses emphasize that the mechanistic origins of and the implications for plasticity heterogeneities need quantitative characterization across brain regions, particularly focusing on context-specific encoding of learned behavior.

Structurally distinct polymorphs of Tau aggregates revealed by nanoscale infrared spectroscopy

Aggregation of the tau protein plays a central role in several neurodegenerative diseases collectively known as tauopathies, including Alzheimers and Parkinsons disease. Tau misfolds into fibrillar beta sheet structures that constitute the paired helical filaments found in Neurofibrillary tangles. It is known that there can be significant structural heterogeneities in tau aggregates associated with different diseases. However, while structures of mature fibrils have been studied, the structural distributions in early stage tau aggregates is not well understood. In the present study, we use AFM-IR to investigate nanoscale spectra of individual tau fibrils at different stages of aggregation and demonstrate the presence of multiple fibrillar polymorphs that exhibit different secondary structures. We further show that mature fibrils contain significant amounts of antiparallel beta sheets. Our results are the very first application of nanoscale infrared spectroscopy to tau aggregates and underscore the promise of spatially resolved infrared spectroscopy for investigating protein aggregation.