Holding information in working memory (WM) is an active and effortful process that is accompanied by sustained load-dependent changes in oscillatory brain activity. These proportional power increases ...are often reported in EEG studies recording theta over frontal midline sites. Intracranial recordings, however, yield mixed results, depending on the brain area being recorded from. We recorded intracranial EEG with depth electrodes in 13 patients with epilepsy who were performing a Sternberg WM task. Here, we investigated patterns of theta power changes as a function of memory load during maintenance in three areas critical for WM: dorsolateral prefrontal cortex (DLPFC), dorsal ACC (dACC), and hippocampus. Theta frequency power in both hippocampus and dACC increased during maintenance. In contrast, theta frequency power in the DLPFC decreased during maintenance, and this decrease was proportional to memory load. Only the power decreases in DLPFC, but not the power increases in hippocampus and dACC, were predictive of behavior in a given trial. The extent of the load-related theta power decreases in the DLPFC in a given participant predicted a participant's RTs, revealing that DLPFC theta explains individual differences in WM ability between participants. Together, these data reveal a pattern of theta power decreases in the DLPFC that is predictive of behavior and that is opposite of that in other brain areas. This result suggests that theta band power changes serve different cognitive functions in different brain areas and specifically that theta power decreases in DLPFC have an important role in maintenance of information.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The influence of groundwater dynamics on the energy balance at the land surface is studied using an integrated, distributed watershed modeling platform. This model includes the mass and energy ...balance at the land surface; three‐dimensional variably saturated subsurface flow; explicit representation of the water table; and overland flow. The model is applied to the Little Washita watershed in Central Oklahoma, USA and compared to runoff, soil moisture and energy flux observations. The connection between groundwater dynamics and the land surface energy balance is studied using a variety of conventional and spatial statistical measures. For a number of energy variables a strong interconnection is demonstrated with water table depth. This connection varies seasonally and spatially depending on the spatial composition of water table depth. A theoretical critical water table depth range is presented where a strong sensitivity between groundwater and land‐surface processes may be observed. For this particular watershed, a critical depth range is established between 1 and 5 m in which the land surface energy budget is most sensitive to groundwater storage. Finally, concrete recommendations are put forth to characterize this interconnection in the field.
Many of the scientific and societal challenges in understanding and preparing for global environmental change rest upon our ability to understand and predict the water cycle change at large river ...basin, continent, and global scales. However, current large‐scale land models (as a component of Earth System Models, or ESMs) do not yet reflect the best hydrologic process understanding or utilize the large amount of hydrologic observations for model testing. This paper discusses the opportunities and key challenges to improve hydrologic process representations and benchmarking in ESM land models, suggesting that (1) land model development can benefit from recent advances in hydrology, both through incorporating key processes (e.g., groundwater‐surface water interactions) and new approaches to describe multiscale spatial variability and hydrologic connectivity; (2) accelerating model advances requires comprehensive hydrologic benchmarking in order to systematically evaluate competing alternatives, understand model weaknesses, and prioritize model development needs, and (3) stronger collaboration is needed between the hydrology and ESM modeling communities, both through greater engagement of hydrologists in ESM land model development, and through rigorous evaluation of ESM hydrology performance in research watersheds or Critical Zone Observatories. Such coordinated efforts in advancing hydrology in ESMs have the potential to substantially impact energy, carbon, and nutrient cycle prediction capabilities through the fundamental role hydrologic processes play in regulating these cycles.
Key Points:
Land model development can benefit from recent advances in hydrology
Accelerating modeling advances requires comprehensive benchmarking activities
Stronger collaboration is needed between the hydrology and ESM modeling communities
A practical guide to large-scale docking Bender, Brian J; Gahbauer, Stefan; Luttens, Andreas ...
Nature protocols,
10/2021, Letnik:
16, Številka:
10
Journal Article
Recenzirano
Odprti dostop
Structure-based docking screens of large compound libraries have become common in early drug and probe discovery. As computer efficiency has improved and compound libraries have grown, the ability to ...screen hundreds of millions, and even billions, of compounds has become feasible for modest-sized computer clusters. This allows the rapid and cost-effective exploration and categorization of vast chemical space into a subset enriched with potential hits for a given target. To accomplish this goal at speed, approximations are used that result in undersampling of possible configurations and inaccurate predictions of absolute binding energies. Accordingly, it is important to establish controls, as are common in other fields, to enhance the likelihood of success in spite of these challenges. Here we outline best practices and control docking calculations that help evaluate docking parameters for a given target prior to undertaking a large-scale prospective screen, with exemplification in one particular target, the melatonin receptor, where following this procedure led to direct docking hits with activities in the subnanomolar range. Additional controls are suggested to ensure specific activity for experimentally validated hit compounds. These guidelines should be useful regardless of the docking software used. Docking software described in the outlined protocol (DOCK3.7) is made freely available for academic research to explore new hits for a range of targets.
Governing Well after War Shair-Rosenfield, Sarah; Wood, Reed M.
The Journal of politics,
07/2017, Letnik:
79, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Previous studies suggest that women’s access to political power often increases following the termination of civil conflicts, particularly those ending in negotiated settlement. However, the effect ...of these changes has received limited attention. We argue that the proportion of female representatives in a national legislature prolongs peace following a negotiated settlement. Moreover, we highlight two mechanisms through which greater female representation reduces the risk of conflict recurrence: (1) by prioritizing social welfare spending over military spending and (2) by improving public perceptions of good governance and the credibility of political elites. We further argue that legislative independence and authority conditions this relationship, implying that greater female representation is more likely to promote peace in states with nominally democratic political institutions. Our empirical analyses of peace duration following negotiated settlements between 1946 and 2011 provide robust support for our general argument and the underlying mechanisms we believe drive this relationship.
This study introduces an unexplored method to synthesize and program liquid-crystalline elastomers (LCEs) based on a two-stage thiol–acrylate Michael addition and photopolymerization (TAMAP) ...reaction. This methodology can be used to program permanently-aligned monodomain samples capable of “hands-free” shape switching as well as offer spatio-temporal control over liquid-crystalline behaviour. LCE networks were shown to have a cytocompatible response at both stages of the reaction.
While intended as a nonviolent foreign policy alternative to military intervention, sanctions have often worsened humanitarian and human rights conditions in the target country. This article examines ...the relationship between economic sanctions and state-sponsored repression of human rights. Drawing on both the public choice and institutional constraints literature, I argue that the imposition of economic sanctions negatively impacts human rights conditions in the target state by encouraging incumbents to increase repression. Specifically, sanctions threaten the stability of target incumbents, leading them to augment their level of repression in an effort to stabilize the regime, protect core supporters, minimize the threat posed by potential challengers, and suppress popular dissent. The empirical results support this theory. These findings provide further evidence that sanctions impose political, social, and physical hardship on civilian populations. They also underscore a need for improvements in current strategies and mechanisms by which states pursue foreign-policy goals and the international community enforces international law and stability.
The neuromodulator melatonin synchronizes circadian rhythms and related physiological functions through the actions of two G-protein-coupled receptors: MT
and MT
. 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
. The two receptors are established drug targets for aligning circadian phase to this cycle in disorders of sleep
and depression
. Despite their importance, few in vivo active MT
-selective ligands have been reported
, hampering both the understanding of circadian biology and the development of targeted therapeutics. Here we docked more than 150 million virtual molecules to an MT
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 MT
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 MT
-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 MT
- but not in MT
-knockout mice. This study illustrates the opportunities for modulating melatonin receptor biology through MT
-selective ligands and for the discovery of previously undescribed, in vivo active chemotypes from structure-based screens of diverse, ultralarge libraries.
Commercial beekeepers transporting honey bees across the United States to provide almond pollination services have reported honey bee deaths, possibly due to pesticide applications made during crop ...bloom. Pesticides are often applied as “tank mixes”, or mixtures of fungicides and insecticides combined into a single application. Spray adjuvants are often added to tank mixes to improve the application characteristics of a pesticide and include spreaders, stickers, or surfactants. The goal of this research was to determine toxicity of adjuvants to adult worker honey bees, both when applied alone and in adjuvant-pesticide tank mixtures. Field-relevant combinations of formulated products were applied to 3-day-old adult worker honey bees using a Potter Spray Tower, and mortality was assessed 48 h following exposure. Adjuvants tested included Activator-90, Attach, Choice Weather Master, Cohere, Dyne-Amic, Induce, Kinetic, LI 700, Liberate, Nu-Film P, PHT Latron B-1956, and Surf-90; fungicides tested include Luna Sensation (Fluopyram and Trifloxystrobin), Pristine (Pyraclostrobin and Boscalid), Tilt (Propiconazole), and Vangard (Cyprodinil), and insecticides tested include Altacor (Chlorantraniliprole), Intrepid 2F (Methoxyfenozide), and a positive control Mustang Maxx (Zeta-cypermethrin). Results demonstrated that exposure to some adjuvants causes acute honey bee mortality at near-field application rates, both when applied alone and in combination with pesticides. Some adjuvant-pesticide combinations demonstrated increased toxicity compared with the adjuvant alone, while others demonstrated decreased toxicity. A better understanding of adjuvant and adjuvant-pesticide tank mixture toxicity to honey bees will play a key role in informing “Best Management Practices” for pesticide applicators using spray adjuvants during bloom when honey bee exposure is likely.
Hydrological modelling is an important tool for research, policy, and management, but uncertainty remains about parameters transferability from field observations made at small scale to models at the ...catchment scale and larger. This uncertainty compels the need to develop parameter relationships that are translatable across scale. In this study, we compare the changes to modelled processes as resolution is coarsened from 100‐m to 1‐km in a topographically complex, 255‐km2 Colorado River headwater catchment. We conducted a sensitivity analysis for hydraulic conductivity (K) and Manning's n parameters across four orders of magnitude. Results showed that K acts as a moderator between surface and subsurface contributions to streamflow, whereas n moderates the duration of high intensity, infiltration‐excess flow. The parametric sensitivity analysis informed development of a new method to scale effective hydraulic conductivity across modelling resolutions in order to compensate for the loss of topographic gradients as resolution is coarsened. A similar mathematical relationship between n and lateral resolution changes was not found, possibly because n is also sensitive to time discretization. This research provides an approach to translate hydraulic conductivity parameters from a calibrated coarse model to higher resolutions where the number of simulations are limited by computational demand.
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