Restriction of task processing time affects cortical activity during processing of a cognitive task: an event-related slow cortical potential study

As is known from psychometrics, restriction of task processing time by the instruction to respond as quickly and accurately as possible leads to task-unspecific cognitive processing. Since this task processing mode is used in most functional neuroimaging studies of human cognition, this may evoke cortical activity that is functionally not essential for the particular task under investigation. Using topographic recordings of event-related slow cortical potentials, two experiments have been performed to investigate whether cortical activity during processing of a visuo-spatial imagery task is substantially influenced by the time provided to process the task. Furthermore, it was investigated whether this effect is additionally modulated by a subject’s task-specific ability. The instruction to respond as quickly and accurately as possible led to increased negative slow cortical potential amplitudes over parietal and frontal regions and significantly interacted with task-specific ability. While cortical activity recorded over parietal and frontal regions was different between subjects with low and high spatial ability when processing time was unrestricted, no such differences were found between ability groups when subjects were instructed to answer both quickly and accurately. These results suggest that restricting processing time has considerable effects on the amount and the pattern of brain activity during cognitive processing and should be taken into account more explicitly in the experimental design and interpretation of neuroimaging studies of cognition

challenges and institutional arrangements

Adaptation to climate change has become an integral part of climate change policies across the world. Based on the limited literature on the governance of climate change adaptation, the paper first highlights four key challenges governments face in this context, i.e. (i) how to better integrate adaptation policies horizontally across policy sectors and (ii) vertically across levels of government, (iii) how to integrate knowledge in adaptation policy decisions, and (iv) how to involve stakeholders in adaptation decisions. The paper then shows how selected OECD countries address these challenges when developing and implementing adaptation policies and instruments. We identify the most important governance mechanisms on the national level which constitute a distinct governance structure in each surveyed country, and highlight their objectives and specific foci on one or more governance challenges. The paper analyses dominant modes of emerging interaction patterns in the respective governance arrangements.Draft pape

On the Complexity of Partitioning Graphs for Arc-Flags

Precomputation of auxiliary data in an additional off-line step is a common approach towards improving the performance of shortest-path queries in large-scale networks. One such technique is the arc-flags algorithm, where the preprocessing involves computing a partition of the input graph. The quality of this partition significantly affects the speed-up observed in the query phase. It is evaluated by considering the search-space size of subsequent shortest-path queries, in particular its maximum or its average over all queries. In this paper, we substantially strengthen existing hardness results of Bauer et al. and show that optimally filling this degree of freedom is NP-hard for trees with unit-length edges, even if we bound the height or the degree. On the other hand, we show that optimal partitions for paths can be computed efficiently and give approximation algorithms for cycles and trees

25th Anniversary Article: A Soft Future: From Robots and Sensor Skin to Energy Harvesters

Scientists are exploring elastic and soft forms of robots, electronic skin and energy harvesters, dreaming to mimic nature and to enable novel applications in wide fields, from consumer and mobile appliances to biomedical systems, sports and healthcare. All conceivable classes of materials with a wide range of mechanical, physical and chemical properties are employed, from liquids and gels to organic and inorganic solids. Functionalities never seen before are achieved. In this review we discuss soft robots which allow actuation with several degrees of freedom. We show that different actuation mechanisms lead to similar actuators, capable of complex and smooth movements in 3d space. We introduce latest research examples in sensor skin development and discuss ultraflexible electronic circuits, light emitting diodes and solar cells as examples. Additional functionalities of sensor skin, such as visual sensors inspired by animal eyes, camouflage, self-cleaning and healing and on-skin energy storage and generation are briefly reviewed. Finally, we discuss a paradigm change in energy harvesting, away from hard energy generators to soft ones based on dielectric elastomers. Such systems are shown to work with high energy of conversion, making them potentially interesting for harvesting mechanical energy from human gait, winds and ocean waves

Memory-Like Inflammatory Responses of Microglia to Rising Doses of LPS: Key Role of PI3Kγ

Trained immunity and immune tolerance have been identified as long-term response patterns of the innate immune system. The causes of these opposing reactions remain elusive. Here, we report about differential inflammatory responses of microglial cells derived from neonatal mouse brain to increasing doses of the endotoxin LPS. Prolonged priming with ultra-low LPS doses provokes trained immunity, i.e., increased production of pro-inflammatory mediators in comparison to the unprimed control. In contrast, priming with high doses of LPS induces immune tolerance, implying decreased production of inflammatory mediators and pronounced release of anti-inflammatory cytokines. Investigation of the signaling processes and cell functions involved in these memory-like immune responses reveals the essential role of phosphoinositide 3-kinase γ (PI3Kγ), one of the phosphoinositide 3-kinase species highly expressed in innate immune cells. Together, our data suggest profound influence of preceding contacts with pathogens on the immune response of microglia. The impact of these interactions—trained immunity or immune tolerance—appears to be shaped by pathogen dose

Memory-Like Responses of Brain Microglia Are Controlled by Developmental State and Pathogen Dose

Microglia, the innate immune cells of the central nervous system, feature adaptive immune memory with implications for brain homeostasis and pathologies. However, factors involved in the emergence and regulation of these opposing responses in microglia have not been fully addressed. Recently, we showed that microglia from the newborn brain display features of trained immunity and immune tolerance after repeated contact with pathogens in a dose-dependent manner. Here, we evaluate the impact of developmental stage on adaptive immune responses of brain microglia after repeated challenge with ultra-low (1 fg/ml) and high (100 ng/ml) doses of the endotoxin LPS in vitro. We find that priming of naïve microglia derived from newborn but not mature and aged murine brain with ultra-low LPS significantly increased levels of pro-inflammatory mediators TNF-α, IL-6, IL-1β, MMP-9, and iNOS as well as neurotrophic factors indicating induction of trained immunity (p \u3c 0.05). In contrast, stimulation with high doses of LPS led to a robust downregulation of pro-inflammatory cytokines and iNOS independent of the developmental state, indicating induced immune tolerance. Furthermore, high-dose priming with LPS upregulated anti-inflammatory mediators IL-10, Arg-1, TGF- β, MSR1, and IL-4 in newborn microglia (p \u3c 0.05). Our data indicate pronounced plasticity of the immune response of neonate microglia compared with microglia derived from mature and aged mouse brain. Induced trained immunity after priming with ultra-low LPS doses may be responsible for enhanced neuro-inflammatory susceptibility of immature brain. In contrast, the immunosuppressed phenotype following high-dose LPS priming might be prone to attenuate excessive damage after recurrent systemic inflammation

The Role of the Pathogen Dose and PI3Kγ in Immunometabolic Reprogramming of Microglia for Innate Immune Memory

Microglia, the innate immune cells of the CNS, exhibit long-term response changes indicative of innate immune memory (IIM). Our previous studies revealed IIM patterns of microglia with opposing immune phenotypes: trained immunity after a low dose and immune tolerance after a high dose challenge with pathogen-associated molecular patterns (PAMP). Compelling evidence shows that innate immune cells adopt features of IIM via immunometabolic control. However, immunometabolic reprogramming involved in the regulation of IIM in microglia has not been fully addressed. Here, we evaluated the impact of dose-dependent microglial priming with ultra-low (ULP, 1 fg/mL) and high (HP, 100 ng/mL) lipopolysaccharide (LPS) doses on immunometabolic rewiring. Furthermore, we addressed the role of PI3Kγ on immunometabolic control using naïve primary microglia derived from newborn wild-type mice, PI3Kγ-deficient mice and mice carrying a targeted mutation causing loss of lipid kinase activity. We found that ULP-induced IIM triggered an enhancement of oxygen consumption and ATP production. In contrast, HP was followed by suppressed oxygen consumption and glycolytic activity indicative of immune tolerance. PI3Kγ inhibited glycolysis due to modulation of cAMP-dependent pathways. However, no impact of specific PI3Kγ signaling on immunometabolic rewiring due to dose-dependent LPS priming was detected. In conclusion, immunometabolic reprogramming of microglia is involved in IIM in a dose-dependent manner via the glycolytic pathway, oxygen consumption and ATP production: ULP (ultra-low-dose priming) increases it, while HP reduces it