Phase of Spontaneous Slow Oscillations during Sleep Influences Memory-Related Processing of Auditory Cues.

UNLABELLED: Slow oscillations during slow-wave sleep (SWS) may facilitate memory consolidation by regulating interactions between hippocampal and cortical networks. Slow oscillations appear as high-amplitude, synchronized EEG activity, corresponding to upstates of neuronal depolarization and downstates of hyperpolarization. Memory reactivations occur spontaneously during SWS, and can also be induced by presenting learning-related cues associated with a prior learning episode during sleep. This technique, targeted memory reactivation (TMR), selectively enhances memory consolidation. Given that memory reactivation is thought to occur preferentially during the slow-oscillation upstate, we hypothesized that TMR stimulation effects would depend on the phase of the slow oscillation. Participants learned arbitrary spatial locations for objects that were each paired with a characteristic sound (eg, cat-meow). Then, during SWS periods of an afternoon nap, one-half of the sounds were presented at low intensity. When object location memory was subsequently tested, recall accuracy was significantly better for those objects cued during sleep. We report here for the first time that this memory benefit was predicted by slow-wave phase at the time of stimulation. For cued objects, location memories were categorized according to amount of forgetting from pre- to post-nap. Conditions of high versus low forgetting corresponded to stimulation timing at different slow-oscillation phases, suggesting that learning-related stimuli were more likely to be processed and trigger memory reactivation when they occurred at the optimal phase of a slow oscillation. These findings provide insight into mechanisms of memory reactivation during sleep, supporting the idea that reactivation is most likely during cortical upstates. SIGNIFICANCE STATEMENT: Slow-wave sleep (SWS) is characterized by synchronized neural activity alternating between active upstates and quiet downstates. The slow-oscillation upstates are thought to provide a window of opportunity for memory consolidation, particularly conducive to cortical plasticity. Recent evidence shows that sensory cues associated with previous learning can be delivered subtly during SWS to selectively enhance memory consolidation. Our results demonstrate that this behavioral benefit is predicted by slow-oscillation phase at stimulus presentation time. Cues associated with high versus low forgetting based on analysis of subsequent recall performance were delivered at opposite slow-oscillation phases. These results provide evidence of an optimal slow-oscillation phase for memory consolidation during sleep, supporting the idea that memory processing occurs preferentially during cortical upstates

Rivulet Flow In Vertical Parallel-Wall Channel

In comparison with studies of rivulet flow over external surfaces, rivulet flow confined by two surfaces has received almost no attention. Fully-developed rivulet flow in vertical parallel-wall channels was characterized, both experimentally and analytically for flows intermediate between a lower flow limit of drop flow and an upper limit where the rivulets meander. Although this regime is the most simple rivulet flow regime, it does not appear to have been previously investigated in detail. Experiments were performed that measured rivulet widths for aperture spacing ranging from 0.152 mm to 0.914 mm. The results were compared with a simple steadystate analytical model for laminar flow. The model divides the rivulet cross-section into an inner region, which is dominated by viscous and gravitational forces and where essentially all flow is assumed to occur, and an outer region, dominated by capillary forces, where the geometry is determined by the contact angle between the fluid and the wall. Calculations using the model provided excellent agreement with data for inner rivulet widths and good agreement with measurements of outer rivulet widths

Development Of An Experiment For Measuring Flow Phenomena Occurring In A Lower Plenum For VHTR CFD Assessment

The objective of the present report is to document the design of our first experiment to measure generic flow phenomena expected to occur in the lower plenum of a typical prismatic VHTR (Very High Temperature Reactor) concept. In the process, fabrication sketches are provided for the use of CFD (computational fluid dynamics) analysts wishing to employ the data for assessment of their proposed codes. The general approach of the project is to develop new benchmark experiments for assessment in parallel with CFD and coupled CFD/systems code calculations for the same geometry. One aspect of the complex flow in a prismatic VHTR is being addressed: flow and thermal mixing in the lower plenum ("hot streaking" issue). Current prismatic VHTR concepts were examined to identify their proposed flow conditions and geometries over the range from normal operation to decay heat removal in a pressurized cooldown. Approximate analyses were applied to determine key non-dimensional parameters and their magnitudes over this operating range. The flow in the lower plenum can locally be considered to be a situation of multiple jets into a confined crossflow -- with obstructions. Flow is expected to be turbulent with momentum-dominated turbulent jets entering; buoyancy influences are estimated to be negligible in normal full power operation. Experiments are needed for the combined features of the lower plenum flows. Missing from the typical jet experiments available are interactions with nearby circular posts and with vertical posts in the vicinity of vertical walls - with near stagnant surroundings at one extreme and significant crossflow at the other

A Rapid Crosstalk of Human γδ T Cells and Monocytes Drives the Acute Inflammation in Bacterial Infections

Vγ9/Vδ2 T cells are a minor subset of T cells in human blood and differ from other T cells by their immediate responsiveness to microbes. We previously demonstrated that the primary target for Vγ9/Vδ2 T cells is (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), an essential metabolite produced by a large range of pathogens. Here we wished to study the consequence of this unique responsiveness in microbial infection. The majority of peripheral Vγ9/Vδ2 T cells shares migration properties with circulating monocytes, which explains the presence of these two distinct blood cell types in the inflammatory infiltrate at sites of infection and suggests that they synergize in anti-microbial immune responses. Our present findings demonstrate a rapid and HMB-PP-dependent crosstalk between Vγ9/Vδ2 T cells and autologous monocytes that results in the immediate production of inflammatory mediators including the cytokines interleukin (IL)-6, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and oncostatin M (OSM); the chemokines CCL2, CXCL8, and CXCL10; and TNF-related apoptosis-inducing ligand (TRAIL). Moreover, under these co-culture conditions monocytes differentiate within 18 hours into inflammatory dendritic cells (DCs) with antigen-presenting functions. Addition of further microbial stimuli (lipopolysaccharide, peptidoglycan) induces CCR7 and enables these inflammatory DCs to trigger the generation of CD4+ effector αβ T cells expressing IFN-γ and/or IL-17. Importantly, our in vitro model replicates the responsiveness to microbes of effluent cells from peritoneal dialysis (PD) patients and translates directly to episodes of acute PD-associated bacterial peritonitis, where Vγ9/Vδ2 T cell numbers and soluble inflammatory mediators are elevated in patients infected with HMB-PP-producing pathogens. Collectively, these findings suggest a direct link between invading pathogens, microbe-responsive γδ T cells, and monocytes in the inflammatory infiltrate, which plays a crucial role in the early response and the generation of microbe-specific immunity

The macrophage in HIV-1 infection: From activation to deactivation?

Macrophages play a crucial role in innate and adaptative immunity in response to microorganisms and are an important cellular target during HIV-1 infection. Recently, the heterogeneity of the macrophage population has been highlighted. Classically activated or type 1 macrophages (M1) induced in particular by IFN-γ display a pro-inflammatory profile. The alternatively activated or type 2 macrophages (M2) induced by Th-2 cytokines, such as IL-4 and IL-13 express anti-inflammatory and tissue repair properties. Finally IL-10 has been described as the prototypic cytokine involved in the deactivation of macrophages (dM). Since the capacity of macrophages to support productive HIV-1 infection is known to be modulated by cytokines, this review shows how modulation of macrophage activation by cytokines impacts the capacity to support productive HIV-1 infection. Based on the activation status of macrophages we propose a model starting with M1 classically activated macrophages with accelerated formation of viral reservoirs in a context of Th1 and proinflammatory cytokines. Then IL-4/IL-13 alternatively activated M2 macrophages will enter into the game that will stop the expansion of the HIV-1 reservoir. Finally IL-10 deactivation of macrophages will lead to immune failure observed at the very late stages of the HIV-1 disease