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The pH sensitivity variations of Electrolyte-Oxide-Semiconductor (EOS) capacitor with both silanol and amine groups are analyzed in terms of their functional group ratio theoretically and experimentally. The phenomena causing the pH sensitivity variations are explained by the buffer effect of each functional group by using Henderson-Hasselbalch equation to compare the state ratio of the acid and the conjugate base of silanol and amine groups. When p is defined as the amine group fraction among the total functional groups, the theoretical pH sensitivity is relatively high around p = 0.3 or 0.7, but low at p = 0, 0.5 or 1. In addition, EOS capacitors with four types of surface treatments for various p are fabricated and characterized by C-V measurements. The pH sensitivity values of the fabricated EOS capacitors corresponding to all p values fit well with the theoretical results. This work allows to explain the reactions on the surface membrane and the characteristics of the pH sensitivity depending on the functional group ratio.

For ion-sensitive devices with SiO 2 sensing membrane, the pH sensitivity response has been analyzed when additional functional groups are attached on the SiO 2 membrane. A modified Site-Binding model (SBM) and Gouy-Chapman-Stern (GCS) model are used for the theoretical analysis. In the presence of both silanol and amine groups, the highest pH sensitivity can be achieved at a functional group ratio of 1∶3 or 3∶1. The differential capacitance and intrinsic buffer capacity were also compared in order to understand their effects on pH sensitivity.

The attenuation coefficient has proven to be a useful tool in numerous biological applications, but accurate calculation is dependent on the characterization of the confocal effect. This study presents a method to precisely determine the confocal effect and its focal plane within a sample by examining the ratio of two optical coherence tomography (OCT) images. The method can be employed to produce a single-value estimate, or a 2D map of the focal plane accounting for the curvature or tilt within the sample. Furthermore, this method is applicable to data obtained with both high numerical aperture (NA) and low-NA lenses, thereby furthering the applicability of the attenuation coefficient to high-NA OCT data. We test and validate this method using standard samples of Intralipid 20% and 5%, improving the accuracy to 99% from 65% compared to the traditional method and preliminarily show applicability to real biological data of glioblastoma acquired in vivo in a murine model.

SummaryMany genes that affect replicative lifespan (RLS) in the budding yeast Saccharomyces cerevisiae also affect aging in other organisms such as C. elegans and M. musculus. We performed a systematic analysis of yeast RLS in a set of 4,698 viable single-gene deletion strains. Multiple functional gene clusters were identified, and full genome-to-genome comparison demonstrated a significant conservation in longevity pathways between yeast and C. elegans. Among the mechanisms of aging identified, deletion of tRNA exporter LOS1 robustly extended lifespan. Dietary restriction (DR) and inhibition of mechanistic Target of Rapamycin (mTOR) exclude Los1 from the nucleus in a Rad53-dependent manner. Moreover, lifespan extension from deletion of LOS1 is nonadditive with DR or mTOR inhibition, and results in Gcn4 transcription factor activation. Thus, the DNA damage response and mTOR converge on Los1-mediated nuclear tRNA export to regulate Gcn4 activity and aging.

Summary Dietary restriction (DR) increases lifespan and attenuates age-related phenotypes in many organisms; however, the effect of DR on longevity of individuals in genetically heterogeneous populations is not well characterized. Here, we describe a large-scale effort to define molecular mechanisms that underlie genotype-specific responses to DR. The effect of DR on lifespan was determined for 166 single gene deletion strains in Saccharomyces cerevisiae. Resulting changes in mean lifespan ranged from a reduction of 79% to an increase of 103%. Vacuolar pH homeostasis, superoxide dismutase activity, and mitochondrial proteostasis were found to be strong determinants of the response to DR. Proteomic analysis of cells deficient in prohibitins revealed induction of a mitochondrial unfolded protein response (mtUPR), which has not previously been described in yeast. Mitochondrial proteotoxic stress in prohibitin mutants was suppressed by DR via reduced cytoplasmic mRNA translation. A similar relationship between prohibitins, the mtUPR, and longevity was also observed in Caenorhabditis elegans. These observations define conserved molecular processes that underlie genotype-dependent effects of DR that may be important modulators of DR in higher organisms.

Chronological aging of budding yeast cells results in a reduction in subsequent replicative life span through unknown mechanisms. Here we show that dietary restriction during chronological aging delays the reduction in subsequent replicative life span up to at least 23 days of chronological age. We further show that among the viable portion of the control population aged 26 days, individual cells with the lowest mitochondrial membrane potential have the longest subsequent replicative lifespan. These observations demonstrate that dietary restriction modulates a common molecular mechanism linking chronological and replicative aging in yeast and indicate a critical role for mitochondrial function in this process.

There is growing evidence that stochastic events play an important role in determining individual longevity. Studies in model organisms have demonstrated that genetically identical populations maintained under apparently equivalent environmental conditions display individual variation in life span that can be modeled by the Gompertz–Makeham law of mortality. Here, we report that within genetically identical haploid and diploid wild-type populations, shorter-lived cells tend to arrest in a budded state, while cells that arrest in an unbudded state are significantly longer-lived. This relationship is particularly notable in diploid BY4743 cells, where mother cells that arrest in a budded state have a shorter mean life span (25.6 vs. 35.6) and larger coefficient of variance with respect to individual life span (0.42 vs. 0.32) than cells that arrest in an unbudded state. Mutations that cause genomic instability tend to shorten life span and increase the proportion of the population that arrest in a budded state. These observations suggest that randomly occurring damage may contribute to stochasticity during replicative aging by causing a subset of the population to terminally arrest prematurely in the S or G2 phase of the cell cycle.

Chronological and replicative aging have been studied in yeast as alternative paradigms for post-mitotic and mitotic aging, respectively. It has been known for more than a decade that cells of the S288C background aged chronologically in rich medium have reduced replicative lifespan relative to chronologically young cells. Here we report replication of this observation in the diploid BY4743 strain background. We further show that the reduction in replicative lifespan from chronological aging is accelerated when cells are chronologically aged under standard conditions in synthetic complete medium rather than rich medium. The loss of replicative potential with chronological age is attenuated by buffering the pH of the chronological aging medium to 6.0, an intervention that we have previously shown can extend chronological lifespan. These data demonstrate that extracellular acidification of the culture medium can cause intracellular damage in the chronologically aging population that is asymmetrically segregated by the mother cell to limit subsequent replicative lifespan.