A model of motor planning is proposed that relies on energy regulation. The system to be controlled is treated as a point mass, and its motion is governed in part by an artificial (or internal) potential. In this case, the energy to be regulated is also artificial, since it is the sum of real kinetic energy and artificial potential energy. Energy regulation is achieved by enforcing Hamilton's principle of least action to drive the motion. By regulating the energy of the point mass, straight=line reaches or circular orbits can be planned. An extension of a previous model for the striatum is summarized in terms of energy based control. Finally, this extension is discussed in the context of hypokinetic symptoms seen in Parkinson's disease.

A novel methodology for calculating the surface energy of a disordered material was developed and is described here. The method was used to calculate the range of surface energies for {100}, {110}, {111}, and {112} type facets of the disordered rock salt (DRX) cathode material Li2MnO2F, as a function of surface cation and anion decoration. Boltzmann averaging was used to determine average surface energies for each facet which were then used to calculate the equilibrium particle shape. It was found that Li2MnO2F displays predominantly {100} type lithium/fluorine-rich facets favoring a cubic particle shape. The density of states along with electronic structure-based bonding analyses are calculated to rationalize differences observed in surface energy. Importantly, it is found that surface lithium and fluorine lower the surface energy of the majority facets, suggesting that surfaces of Li2MnO2F are likely enriched in lithium and fluorine and display less oxygen and manganese, which has implications for capacity and rate retention.

Objective

A randomized, placebo-controlled, double-blind, multicenter 52-week phase 2 trial of resveratrol in individuals with mild to moderate Alzheimer disease (AD) examined its safety and tolerability and effects on biomarker (plasma Aβ40 and Aβ42, CSF Aβ40, Aβ42, tau, and phospho-tau 181) and volumetric MRI outcomes (primary outcomes) and clinical outcomes (secondary outcomes).

Methods

Participants (n = 119) were randomized to placebo or resveratrol 500 mg orally once daily (with dose escalation by 500-mg increments every 13 weeks, ending with 1,000 mg twice daily). Brain MRI and CSF collection were performed at baseline and after completion of treatment. Detailed pharmacokinetics were performed on a subset (n = 15) at baseline and weeks 13, 26, 39, and 52.

Results

Resveratrol and its major metabolites were measurable in plasma and CSF. The most common adverse events were nausea, diarrhea, and weight loss. CSF Aβ40 and plasma Aβ40 levels declined more in the placebo group than the resveratrol-treated group, resulting in a significant difference at week 52. Brain volume loss was increased by resveratrol treatment compared to placebo.

Conclusions

Resveratrol was safe and well-tolerated. Resveratrol and its major metabolites penetrated the blood-brain barrier to have CNS effects. Further studies are required to interpret the biomarker changes associated with resveratrol treatment.

Classification of evidence

This study provides Class II evidence that for patients with AD resveratrol is safe, well-tolerated, and alters some AD biomarker trajectories. The study is rated Class II because more than 2 primary outcomes were designated.

The extent of increasing anthropogenic impacts on large marine vertebrates partly depends on the animals' movement patterns. Effective conservation requires identification of the key drivers of movement including intrinsic properties and extrinsic constraints associated with the dynamic nature of the environments the animals inhabit. However, the relative importance of intrinsic versus extrinsic factors remains elusive. We analyze a global dataset of ∼2.8 million locations from >2,600 tracked individuals across 50 marine vertebrates evolutionarily separated by millions of years and using different locomotion modes (fly, swim, walk/paddle). Strikingly, movement patterns show a remarkable convergence, being strongly conserved across species and independent of body length and mass, despite these traits ranging over 10 orders of magnitude among the species studied. This represents a fundamental difference between marine and terrestrial vertebrates not previously identified, likely linked to the reduced costs of locomotion in water. Movement patterns were primarily explained by the interaction between species-specific traits and the habitat(s) they move through, resulting in complex movement patterns when moving close to coasts compared with more predictable patterns when moving in open oceans. This distinct difference may be associated with greater complexity within coastal microhabitats, highlighting a critical role of preferred habitat in shaping marine vertebrate global movements. Efforts to develop understanding of the characteristics of vertebrate movement should consider the habitat(s) through which they move to identify how movement patterns will alter with forecasted severe ocean changes, such as reduced Arctic sea ice cover, sea level rise, and declining oxygen content.