Mitochondria have a central role in ageing. They are considered to be both a target of the ageing process and a contributor to it. Alterations in mitochondrial structure and function are evident during ageing in most eukaryotes, but how this occurs is poorly understood. Here we identify a functional link between the lysosome-like vacuole and mitochondria in Saccharomyces cerevisiae, and show that mitochondrial dysfunction in replicatively aged yeast arises from altered vacuolar pH. We found that vacuolar acidity declines during the early asymmetric divisions of a mother cell, and that preventing this decline suppresses mitochondrial dysfunction and extends lifespan. Surprisingly, changes in vacuolar pH do not limit mitochondrial function by disrupting vacuolar protein degradation, but rather by reducing pH-dependent amino acid storage in the vacuolar lumen. We also found that calorie restriction promotes lifespan extension at least in part by increasing vacuolar acidity via conserved nutrient-sensing pathways. Interestingly, although vacuolar acidity is reduced in aged mother cells, acidic vacuoles are regenerated in newborn daughters, coinciding with daughter cells having a renewed lifespan potential. Overall, our results identify vacuolar pH as a critical regulator of ageing and mitochondrial function, and outline a potentially conserved mechanism by which calorie restriction delays the ageing process. Because the functions of the vacuole are highly conserved throughout evolution, we propose that lysosomal pH may modulate mitochondrial function and lifespan in other eukaryotic cells.
Continent-scale biogeography has been extensively studied in soils and marine systems, but little is known about biogeographical patterns in non-marine sediments. We used barcode pyrosequencing to quantify the effects of local geochemical properties and geographic distance for bacterial community structure and membership, using sediment samples from 15 lakes on the Tibetan Plateau (4–1670 km apart). Bacterial communities were surprisingly diverse, and distinct from soil communities. Four of 26 phyla detected were dominant: Proteobacteria, Bacteroidetes, Firmicutes and Actinobacteria, albeit 20.2% of sequences were unclassified at the phylum level. As previously observed in acidic soil, pH was the dominant factor influencing alkaline sediment community structure, phylotype richness and phylogenetic diversity. In contrast, archaeal communities were less affected by pH. More geographically distant sites had more dissimilar communities (r = 0.443, P = 0.030). Variance partitioning analysis showed that geographic distance (historical contingencies) contributed more to bacterial community variation (12.2%) than any other factor, although the environmental factors explained more variance when combined (28.9%). Together, our results show that pH is the best predictor of bacterial community structure in alkaline sediments, and confirm that both geographic distance and chemical factors govern bacterial biogeography in lake sediments.
Tristan. M. Lawrie, Gregor. Tanner, Gregory. J. Chaplain
We conceptualise and numerically simulate a resonant metamaterial interface incorporating non-local, or beyond nearest neighbour, coupling that acts as a discrete angular filter. It can be designed to yield perfect transmission at customizable angles of incidence, without diffraction, allowing for tailored transmission in arbitrarily narrow wavenumber windows. The theory is developed in the setting of discrete, infinitely periodic quantum graphs and we realise it numerically as an acoustic meta-grating. The theory is then applied to continuous acoustic waveguides, first for the medium surrounding the interface and then for the interface itself, showing the efficacy of quantum graph theory in interface design.
This report evaluates the applicability of the ideal gas law in the pressurized air-bearing of hard disk drives when calculating the relative humidity. We employ a semi-analytical numerical method that solves vapor-liquid equilibrium using the Redlich-Kwong and Peng-Robinson equation of state to calculate the saturation pressure of water. The deviation from the ideal gas law is quantified and examined through saturation pressure isotherms. We find that at low temperatures, lighter gases such as helium show little deviation from the ideal gas law, whereas heavier gases such as nitrogen deviate significantly. As temperature increases, the difference between the gases decreases. The results suggest that in areas of low temperature, the non-ideal nature of gases must be taken into account.
We describe a process for fabricating a wafer-scale array of alkali metal vapor cells with low residual gas pressure. We show that by etching long, thin channels between the cells on the Si wafer surface, the residual gas pressure in the evacuated vapor cell can be reduced to below 0.5 kPa (4 Torr) with a yield above 50 %. The low residual gas pressure in these mass-producible alkali vapor cells can enable a new generation of low-cost chip-scale atomic devices such as vapor cell optical clocks, wavelength references, and Rydberg sensors.
Standard spring design is based on the assumption that there is no residual stress in the wire. This assumption can be quite strong for small wires that undergo a significant wire drawing during the manufacturing process. The main objective of this work is to design and test a method for characterizing residual stresses in small diameter drawn wires. The basic principle consists in removing a part of the material and then measuring the associated displacements. This material removal was simulated by finite elements and experimented in real situation. The first results are encouraging because they seem to show that the residual stresses in the wire studied are significant, and justify our investigations.
AbstractPolycarbonate‐based micelles possessed enormous potential for hydrophobic drug delivery. To improve micelle stability and prevent premature leakage during blood circulation, photo‐induced thiol‐yne click reaction was utilized to construct polycarbonate‐based core crosslinked micelles (CCLMs), which avoided the use of toxic copper catalyst. The introduced β‐thiopropionate linkage in the core was demonstrated to endow the CCLMs with pH‐responsiveness. The obtained CCLMs showed good dilution stability against DMF and water. Further MTT assays demonstrated excellent biocompatibility and low toxicity of the CCLMs in HeLa/MCF‐7 cells. Moreover, DOX‐encapsulated CCLMs showed good anticancer effects and excellent internalization efficiency in HeLa cells. The pH‐responsive polycarbonate‐based CCLMs by thiol‐yne click reaction have potential used as smart delivery systems for controlled drug release.
Albert R. Gnadt, Allan B. Wollaber, Aaron P. Nielsen
This note is intended to serve as a straightforward reference that summarizes and expands on the linear aeromagnetic compensation model first introduced by Tolles and Lawson in 1950. The Tolles-Lawson model provides a simple, physical representation of an aircraft's magnetic field, composed of permanent, induced, and eddy current terms, and applies an approximation (a Taylor expansion) to enable fitting coefficients with a general linear model. Here, the Tolles-Lawson model is derived, paying stricter attention to where assumptions are made, the model calibration procedure is described, and some additional comments on a second-order correction and a means of constructing the vector aircraft field are provided.