Aβ oligomers are potential targets for the diagnosis and therapy of Alzheimer's disease (AD). On the other hand, the molecule curcumin has been shown to possess significant therapeutic potential in many areas. In this paper, we use all-atom explicit solvent molecular dynamics simulations to study the effect of curcumin on the stability of Aβ amyloid protein oligomers. We observed that curcumin decreases the β-sheet secondary structural content within the Aβ oligomers without reducing the contacts between the monomers. The breaking of the β-sheet is found to be preceded by a deformation of the β-sheet structure due to hydrophobic interaction from the nearby curcumin. Furthermore, the π-stacking interaction between curcumin (keto ring and enol ring) and the aromatic residues of Aβ, which exists throughout the simulations, has also contributed to the diminishing of the β-sheet structure. Our analysis of the underwrapped amide-carbonyl hydrogen bonds reveals several stable dehydrons of the oligomer, especially the dehydron pair 34L and 41I, which curcumin tends to hover over. We have examined the paths of curcumin on the Aβ proteins and determined the common routes where curcumin lingers as it traverses around the Aβ. In consequence, our study has provided a detailed interaction picture between curcumin and the Aβ oligomers.

Bus bunching is a perennial phenomenon that not only diminishes the efficiency of a bus system, but also prevents transit authorities from keeping buses on schedule. We present a physical theory of buses serving a loop of bus stops as a ring of coupled self-oscillators, analogous to the Kuramoto model. Sustained bunching is a repercussion of the process of phase synchronisation whereby the phases of the oscillators are locked to each other. This emerges when demand exceeds a critical threshold. Buses also bunch at low demand, albeit temporarily, due to frequency detuning arising from different human drivers’ distinct natural speeds. We calculate the critical transition when complete phase locking (full synchronisation) occurs for the bus system, and posit the critical transition to completely no phase locking (zero synchronisation). The intermediate regime is the phase where clusters of partially phase locked buses exist. Intriguingly, these theoretical results are in close correspondence to real buses in a university’s shuttle bus system.

In this review, we elucidate the mechanisms of A β oligomer toxicity which may contribute to Alzheimer’s disease (AD). In particular, we discuss on the interaction of A β oligomers with the membrane through the process of adsorption and insertion. Such interaction gives rises to phase transitions in the sub-structures of the A β peptide from α -helical to β -sheet structure. By means of a coarse-grained model, we exhibit the tendency of β -sheet structures to aggregate, thus providing further insights to the process of membrane induced aggregation. We show that the aggregated oligomer causes membrane invagination, which is a precursor to the formation of pore structures and ion channels. Other pathological progressions to AD due to A β oligomers are also covered, such as their interaction with the membrane receptors, and their direct versus indirect effects on oxidative stress and intraneuronal accumulation. We further illustrate that the molecule curcumin is a potential A β toxicity inhibitor as a β -sheet breaker by having a high propensity to interact with certain A β residues without binding to them. The comprehensive understanding gained from these current researches on the various toxicity mechanisms show promises in the provision of better therapeutics and treatment strategies in the near future.

The aggregation of amyloid β peptides resulting in neurotoxic oligomers is an important but yet mysterious process in Alzheimer's disease development. Molecular dynamics simulations were performed to investigate the self-assembly of three full-length amyloid peptides in the zwitterionic dipalmitoylphosphatidylcholine and cholesterol mixed lipid bilayer. During the 1000 ns simulation, the residues 1-27 were found to interact preferentially with the lipid-aqueous interface region, while residues 28-42 show an inclination to remain inside the bilayer hydrophobic tail region. The interaction between peptides and lipids has facilitated the association of Aβ peptides. However, the interaction between cholesterol and peptides is inversely correlated with the extent of the peptide-peptide interactions. Our simulation has uncovered the formation of a short segment of parallel β-sheet between two peptide chains. In another chain, the N- and C-termini came close to each other. All the structural transitions indicate that our simulation has caught a glimpse of the complicated peptide oligomerization process. The full understanding of the underlying mechanism still requires further experimental and theoretical studies.

We investigate a no-boarding policy in a system of N buses serving M bus stops in a loop, which is an entrainment mechanism to keep buses synchronised in a reasonably staggered configuration.Buses always allow alighting, but would disallow boarding if certain criteria are met. We let buses move with the same natural speed (applicable to programmable self-driving buses) and analytically calculate the average waiting time experienced by passengers waiting at the bus stop for a bus to arrive. Our analytical results show that a no-boarding policy can dramatically reduce the average waiting time, as compared to the usual situation without the no-boarding policy. Subsequently, we carry out simulations to verify these theoretical analyses, also extending the simulations to typical human-driven buses with different natural speeds based on real data. Finally, we describe a simple general adaptive algorithm to dynamically determine when to implement no-boarding.

We perform a high-accuracy moment analysis of the avalanche size, duration and area distribution of the Abelian Manna model on eight two-dimensional and four one-dimensional lattices. The results provide strong support to establish universality of exponents and moment ratios across different lattices and a good survey for the strength of corrections to scaling which are notorious in the Manna universality class. The results are compared against previous work done on Manna model, Oslo model and directed percolation. We also confirm hypothesis of various scaling relations.

Spatial patterning often occurs in ecosystems as a result of a selforganizing process caused by feedback between organisms and the physical environment. Here, we show that the spatial patterns observable in centuries-old Balinese rice terraces are also created by feedback between farmers' decisions and the ecology of the paddies, which triggers a transition from local to globalscale control of water shortages and rice pests. We propose an evolutionary game, based on local farmers' decisions that predicts specific power laws in spatial patterning that are also seen in a multispectral image analysis of Balinese rice terraces. The model shows how feedbacks between human decisions and ecosystem processes can evolve toward an optimal state in which total harvests are maximized and the system approaches Pareto optimality. It helps explain how multiscale cooperation from the community to the watershed scale could persist for centuries, and why the disruption of this self-organizing system by the Green Revolution caused chaos in irrigation and devastating losses from pests. The model shows that adaptation in a coupled human-natural system can trigger self-organized criticality (SOC). In previous exogenously driven SOC models, adaptation plays no role, and no optimization occurs. In contrast, adaptive SOC is a self-organizing process where local adaptations drive the system toward local and global optima.self-organization | criticality | irrigation | evolutionary games | Pareto optimality T he geometric precision of Balinese rice terraces has inspired generations of postcard photographers. Viewed from above, a changing mosaic of colors appears: green when the rice is young, yellow as it nears harvest, silver when the paddies are flooded, and brown when they are drained. These colors are not uniform across the island, because Bali is an equatorial island with only two seasons, wet and dry. Consequently, farmers can plant their crops at any time, although they avoid harvesting in the rainy season. The colored patches that make up the mosaics are visible in Google Earth. Like many natural phenomena, patches show a characteristic power-law distribution of sizes. However, in this case, the patches are created by the farmer's decisions about when to synchronize irrigation schedules with their neighbors: Each patch displays the outcome of these choices. Adjacent patches tend to be correlated. This correlation weakens with distance, a relationship that also follows a specific power law (Fig. 1). To discover why harvests approach a maximum when both the size distribution of patches and the corresponding correlation functions fit power-law distributions, we need a model that relates the decisions of the farmers to the consequences for irrigation flows and rice growth.In Bali, water is regarded as a public good, the gift of the Goddess of the Lakes. Rice is grown in paddy fields fed by irrigation systems dependent on rainfall. Rainfall varies by season and, in combination with groundwater inflow, determines river flow. By virtue of...

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