Direct numerical simulations of a highly constrained plane Couette flow are employed to study the dynamics of the structures found in the near-wall region of turbulent flows. Starting from a fully developed turbulent flow, the dimensions of the computational domain are reduced to near the minimum values which will sustain turbulence. A remarkably well-defined, quasi-cyclic and spatially organized process of regeneration of near-wall structures is observed. This process is composed of three distinct phases: formation of streaks by streamwise vortices, breakdown of the streaks, and regeneration of the streamwise vortices. Each phase sets the stage for the next, and these processes are analysed in detail. The most novel results concern vortex regeneration, which is found to be a direct result of the breakdown of streaks that were originally formed by the vortices, and particular emphasis is placed on this process. The spanwise width of the computational domain corresponds closely to the typically observed spanwise spacing of near-wall streaks. When the width of the domain is further reduced, turbulence is no longer sustained. It is suggested that the observed spacing arises because the time scales of streak formation, breakdown and vortex regeneration become mismatched when the streak spacing is too small, and the regeneration cycle at that scale is broken.

No abstract

The cerebellum and the integrity of cerebral white matter may play a more significant role in the symptomatology of HD than previously thought. Furthermore, changes in cortical gray and cerebral white matter were related to caudate atrophy, supporting a similar mechanism of degeneration.

Ocean acidification is predicted to occur first in polar oceans. We investigated the saturation state of waters with respect to calcite (Ωcal) and aragonite (Ωarg) in six sections along an Arctic outflow pathway through the Canadian Arctic Archipelago (CAA) and into the northwestern Atlantic using dissolved inorganic carbon and total alkalinity measurements from 2003 to 2005. The study area, a key region connecting the Arctic and the North Atlantic, includes Smith Sound, Barrow Strait, Baffin Bay, Davis Strait, Hudson Strait, and the Labrador Sea. The average Ωarg in the Arctic outflow was 1.18 ± 0.17 in Barrow Strait and 1.31 ± 0.14 in Smith Sound, with areas where Ωarg < 1. The Arctic outflow through the CAA has a high content of Pacific waters, which have a low saturation state. These waters can be traced along the western Baffin Bay to Davis Strait. South of Davis Strait, this outflow is modified by mixing with slope and offshore waters of Atlantic origin and with the outflow from Hudson Strait. Despite the mixing, low saturation state water can still be identified on the southern Labrador Shelf. The aragonite saturation horizon is found at ∼150 m in Barrow Strait; at 200 m in Baffin Bay, Davis Strait, and Hudson Strait; and at 2300 m in the Labrador Sea. This study provides baseline data of the saturation states for the waters of the CAA and the northwest Atlantic. It also illustrates the downstream evolution of low saturation state Arctic outflow in the northwest Atlantic.

Volume and freshwater transport through Lancaster Sound are estimated from mooring measurements collected in eastern Barrow Strait for 13 years between 1998 and 2011. Estimates from 2006 to 2011 confirm the relationship between surface wind and volume transport derived from data collected between 1998 and 2006. Volume transport through Barrow Strait along the Northwest Passage is significantly correlated with northeastward winds in the Beaufort Sea, parallel to the western coasts of the Canadian Arctic Archipelago, at monthly to interannual time scales. The location and wind direction for which there is maximum correlation are consistent with the flow being driven by a sea level difference between opposite ends of the Passage, and the difference being determined by setup caused by alongshore winds in the Beaufort Sea. Monthly alongshore wind anomalies account for 43% of the variance of the transport anomalies (p < 0.01). Examination of the residuals, after subtracting the volume transport driven by the Beaufort Sea winds from the total transport, showed that they are not significantly correlated with winds in Baffin Bay (p > 0.05). The annual cycles of the total volume transport and its part attributed to the Beaufort Sea wind both have peaks in the summer and are lowest in the autumn. Correlations of the volume transport anomaly with ice velocity anomalies are lower than with surface wind anomalies.

Alterations in oxidative metabolism are considered to be one of the major contributors to Huntington's disease (HD) pathogenesis. However, existing data about oxidative metabolism in HD are contradictory. Here, we investigated the effect of mutant huntingtin (mHtt) on oxidative metabolism in YAC128 mice. Both mHtt and wild-type huntingtin (Htt) were associated with mitochondria and the amount of bound Htt was four-times higher than the amount of bound mHtt. Percoll gradient-purified brain synaptic and non-synaptic mitochondria as well as unpurified brain, liver and heart mitochondria, isolated from 2- and 10-month-old YAC128 mice and age-matched WT littermates had similar respiratory rates. There was no difference in mitochondrial membrane potential or ADP and ATP levels. Expression of selected nuclear-encoded mitochondrial proteins in 2- and 10-month-old YAC128 and WT mice was similar. Cultured striatal and cortical neurons from YAC128 and WT mice had similar respiratory and glycolytic activities as measured with Seahorse XF24 analyzer in medium containing 10 mm glucose and 15 mm pyruvate. In the medium with 2.5 mm glucose, YAC128 striatal neurons had similar respiration, but slightly lower glycolytic activity. Striatal neurons had lower maximal respiration compared with cortical neurons. In vivo experiments with YAC128 and WT mice showed similar O2 consumption, CO2 release, physical activity, food consumption and fasted blood glucose. However, YAC128 mice were heavier and had more body fat compared with WT mice. Overall, our data argue against respiratory deficiency in YAC128 mice and, consequently, suggest that mitochondrial respiratory dysfunction is not essential for HD pathogenesis.

Background. Metabolism in the tumor microenvironment can play a critical role in tumorigenesis and tumor aggression. Metabolic coupling may occur between tumor compartments; this phenomenon can be prognostically significant and may be conserved across tumor types. Monocarboxylate transporters (MCTs) play an integral role in cellular metabolism via lactate transport and have been implicated in metabolic synergy in tumors. The transporters MCT1 and MCT4 are regulated via expression of their chaperone, CD147. Methods. We conducted a meta-analysis of existing publications on the relationship between MCT1, MCT4, and CD147 expression and overall survival and disease-free survival in cancer, using hazard ratios derived via multivariate Cox regression analyses. Results. Increased MCT4 expressions in the tumor microenvironment, cancer cells, or stromal cells were all associated with decreased overall survival and decreased disease-free survival (p < 0.001 for all analyses). Increased CD147 expression in cancer cells was associated with decreased overall survival and disease-free survival (p < 0.0001 for both analyses). Few studies were available on MCT1 expression; MCT1 expression was not clearly associated with overall or disease-free survival. Conclusion. MCT4 and CD147 expression correlate with worse prognosis across many cancer types. These results warrant further investigation of these associations.

We investigated Ca2+ handling in isolated brain synaptic and nonsynaptic mitochondria and in cultured striatal neurons from the YAC128 mouse model of Huntington’s disease (HD). Both synaptic and nonsynaptic mitochondria from 2- and 12-month-old YAC128 mice had larger Ca2+ uptake capacity than mitochondria from YAC18 and wild-type FVB/NJ mice. Synaptic mitochondria from 12-month-old YAC128 mice had further augmented Ca2+ capacity compared with mitochondria from 2-month-old YAC128 mice and age-matched YAC18 and FVB/NJ mice. This increase in Ca2+ uptake capacity correlated with an increase in the amount of mutant huntingtin protein (mHtt) associated with mitochondria from 12-month-old YAC128 mice. We speculate that this may happen due to mHtt-mediated sequestration of free fatty acids thereby increasing resistance of mitochondria to Ca2+-induced damage. In experiments with striatal neurons from YAC128 and FVB/NJ mice, brief exposure to 25 or 100μM glutamate produced transient elevations in cytosolic Ca2+ followed by recovery to near resting levels. Following recovery of cytosolic Ca2+, mitochondrial depolarization with FCCP produced comparable elevations in cytosolic Ca2+, suggesting similar Ca2+ release and, consequently, Ca2+ loads in neuronal mitochondria from YAC128 and FVB/NJ mice. Together, our data argue against a detrimental effect of mHtt on Ca2+ handling in brain mitochondria of YAC128 mice.