资源环境科技发展态势分析平台

Aluminium- and gallium-doped iron compounds show a large anomalous Nernst effect owing to a topological electronic structure, and their films are potentially suitable for designing low-cost, flexible microelectronic thermoelectric generators.

Thermoelectric generation using the anomalous Nernst effect (ANE) has great potential for application in energy harvesting technology because the transverse geometry of the Nernst effect should enable efficient, large-area and flexible coverage of a heat source. For such applications to be viable, substantial improvements will be necessary not only for their performance but also for the associated material costs, safety and stability. In terms of the electronic structure, the anomalous Nernst effect (ANE) originates from the Berry curvature of the conduction electrons near the Fermi energy(1,2). To design a large Berry curvature, several approaches have been considered using nodal points and lines in momentum space(3-10). Here we perform a high-throughput computational search and find that 25 percent doping of aluminium and gallium in alpha iron, a naturally abundant and low-cost element, dramatically enhances the ANE by a factor of more than ten, reaching about 4 and 6 microvolts per kelvin at room temperature, respectively, close to the highest value reported so far. The comparison between experiment and theory indicates that the Fermi energy tuning to the nodal web-a flat band structure made of interconnected nodal lines-is the key for the strong enhancement in the transverse thermoelectric coefficient, reaching a value of about 5 amperes per kelvin per metre with a logarithmic temperature dependence. We have also succeeded in fabricating thin films that exhibit a large ANE at zero field, which could be suitable for designing low-cost, flexible microelectronic thermoelectric generators(11-13).

The neuromodulator melatonin synchronizes circadian rhythms and related physiological functions through the actions of two G-protein-coupled receptors: MT1 and MT2. Circadian release of melatonin at night from the pineal gland activates melatonin receptors in the suprachiasmatic nucleus of the hypothalamus, synchronizing the physiology and behaviour of animals to the light-dark cycle(1-4). The two receptors are established drug targets for aligning circadian phase to this cycle in disorders of sleep(5,6) and depression(1-4,7-9). Despite their importance, few in vivo active MT1-selective ligands have been reported(2,8,10-12), hampering both the understanding of circadian biology and the development of targeted therapeutics. Here we docked more than 150 million virtual molecules to an MT1 crystal structure, prioritizing structural fit and chemical novelty. Of these compounds, 38 high-ranking molecules were synthesized and tested, revealing ligands with potencies ranging from 470 picomolar to 6 micromolar. Structure-based optimization led to two selective MT1 inverse agonists-which were topologically unrelated to previously explored chemotypes-that acted as inverse agonists in a mouse model of circadian re-entrainment. Notably, we found that these MT1-selective inverse agonists advanced the phase of the mouse circadian clock by 1.3-1.5 h when given at subjective dusk, an agonist-like effect that was eliminated in MT1- but not in MT2-knockout mice. This study illustrates the opportunities for modulating melatonin receptor biology through MT1-selective ligands and for the discovery of previously undescribed, in vivo active chemotypes from structure-based screens of diverse, ultralarge libraries. A computational screen of an ultra-large virtual library against the structure of the melatonin receptor found nanomolar ligands, and ultimately two selective MT1 inverse agonists that induced phase advancement of the mouse circadian clock when given at subjective dusk.

Repositories let researchers store, share and access life-science images - and maybe even extract new findings.

Most cortical synapses are local and excitatory. Local recurrent circuits could implement amplification, allowing pattern completion and other computations(1-4). Cortical circuits contain subnetworks that consist of neurons with similar receptive fields and increased connectivity relative to the network average(5,6). Cortical neurons that encode different types of information are spatially intermingled and distributed over large brain volumes(5-7), and this complexity has hindered attempts to probe the function of these subnetworks by perturbing them individually(8). Here we use computational modelling, optical recordings and manipulations to probe the function of recurrent coupling in layer 2/3 of the mouse vibrissal somatosensory cortex during active tactile discrimination. A neural circuit model of layer 2/3 revealed that recurrent excitation enhances sensory signals by amplification, but only for subnetworks with increased connectivity. Model networks with high amplification were sensitive to damage: loss of a few members of the subnetwork degraded stimulus encoding. We tested this prediction by mapping neuronal selectivity(7) and photoablating(9,10) neurons with specific selectivity. Ablation of a small proportion of layer 2/3 neurons (10-20, less than 5% of the total) representing touch markedly reduced responses in the spared touch representation, but not in other representations. Ablations most strongly affected neurons with stimulus responses that were similar to those of the ablated population, which is also consistent with network models. Recurrence among cortical neurons with similar selectivity therefore drives input-specific amplification during behaviour.

Computational modelling, imaging and single-cell ablation in layer 2/3 of the mouse vibrissal somatosensory cortex reveals that recurrent activity in cortical neurons can drive input-specific amplification during behaviour.