Epigenetic modifications are thought to be important for gene expression changes during development and aging. However, besides the Sir2 histone deacetylase in somatic tissues and H3K4 trimethylation ...in germlines, there is scant evidence implicating epigenetic regulations in aging. The insulin/IGF-1 signaling (IIS) pathway is a major life span regulatory pathway. Here, we show that progressive increases in gene expression and loss of H3K27me3 on IIS components are due, at least in part, to increased activity of the H3K27 demethylase UTX-1 during aging. RNAi of the
utx-1 gene extended the mean life span of
C. elegans by ∼30%, dependent on DAF-16 activity and not additive in
daf-2 mutants. The loss of
utx-1 increased H3K27me3 on the
Igf1r/
daf-2 gene and decreased IIS activity, leading to a more “naive” epigenetic state. Like stem cell reprogramming, our results suggest that reestablishment of epigenetic marks lost during aging might help “reset” the developmental age of animal cells.
► Elevated
utx-1 expression during aging preceded increases in
daf-2 expression ► Reducing
utx-1 gene expression extended the mean life span of
C. elegans by ∼30% ► Life span extension induced by
utx-1 RNAi depended on IIS pathway ► Reducing
utx-1 level promoted H3K27me3 on
daf-2 and a younger epigenetic state
•An estimate for the steady convective flux for anisotropic media is developed.•Steady convective dissolution in anisotropic media scales as (kv/kh)1/2.•Steady convective dissolution in heterogeneous ...models scales in the same fashion.•This theoretical estimate can be used in upscaled models.
Enhanced dissolution of CO2 into a saline aquifer due to convective mixing is an important physical process for the secure long-term storage of significant quantities of CO2. Numerical simulations have previously shown that the dissolution rate of CO2 into reservoir brine will stabilise after a certain time period, with only small oscillations about a long-term average. A theoretical estimate for this average long-term mass flux in an isotropic homogeneous reservoir has previously appeared in the literature. In this paper, an estimate for the steady dissolution rate in anisotropic homogenous porous media is developed using a simple theoretical argument. Detailed numerical simulations confirm that the steady dissolution rate scales as (kvkh)1/2 in an anisotropic homogeneous porous media, where kv and kh are the vertical and horizontal permeabilities, respectively. The scaling is also shown to be appropriate for heterogeneous models where vertical heterogeneity is introduced by including a random distribution of impermeable barriers.
DNA is a compelling alternative to non-volatile information storage technologies due to its information density, stability, and energy efficiency. Previous studies have used artificially synthesized ...DNA to store data and automated next-generation sequencing to read it back. Here, we report digital Nucleic Acid Memory (dNAM) for applications that require a limited amount of data to have high information density, redundancy, and copy number. In dNAM, data is encoded by selecting combinations of single-stranded DNA with (1) or without (0) docking-site domains. When self-assembled with scaffold DNA, staple strands form DNA origami breadboards. Information encoded into the breadboards is read by monitoring the binding of fluorescent imager probes using DNA-PAINT super-resolution microscopy. To enhance data retention, a multi-layer error correction scheme that combines fountain and bi-level parity codes is used. As a prototype, fifteen origami encoded with 'Data is in our DNA!\n' are analyzed. Each origami encodes unique data-droplet, index, orientation, and error-correction information. The error-correction algorithms fully recover the message when individual docking sites, or entire origami, are missing. Unlike other approaches to DNA-based data storage, reading dNAM does not require sequencing. As such, it offers an additional path to explore the advantages and disadvantages of DNA as an emerging memory material.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer related deaths worldwide and its incidence is increasing due to endemic obesity and the growing burden of non-alcoholic ...steatohepatitis (NASH) associated liver cancer. Although much is known about the clinical and histological pathology of NASH-driven HCC in humans, its etiology remains unclear and there is a lack of reliable biomarkers and limited effective therapies. Progress has been hampered by the scarcity of standardized animal models that recapitulate the gradual progression of NASH towards HCC observed in humans. Here we review existing mouse models and their suitability for studying NASH-driven HCC with special emphasis on a preclinical model that we recently developed that faithfully mimics all the clinical endpoints of progression of the human disease. Moreover, it is highly translatable, allows the use of gene-targeted mice, and is suitable for gaining knowledge of how NASH progresses to HCC and development of new targets for treatment.
In the past decade, the Chinese-North Korean border region has undergone a gradual transformation into a site of intensified cooperation, competition, and intrigue. These changes have prompted a ...significant volume of critical scholarship and media commentary across multiple languages and disciplines. Drawing on existing studies and new data, this volume brings much of this literature into concert by pulling together a wide range of insight on the region's economics, security, social cohesion, and information flows. Drawing from multilingual sources and transnational scholarship, the volume is enhanced by the extensive fieldwork undertaken by the editors and contributors in their quest to decode the borderland. In doing so, the volume emphasizes the link between theory, methodology, and practice in the field of Area Studies and social science more broadly.
Inaugural Editorial Green, Christopher D.
History of psychology,
02/2022, Letnik:
25, Številka:
1
Journal Article
Recenzirano
Now in its 25th year, the journal has become an important institution within the discipline since an article of the editor's (on Aristotle's theory of mind) was the first to appear on its pages in ...back in 1998. It is the editor's aim to build the journal in ways that serve the community of historians of psychology even better than it has over the past quarter of a century. First, the editor intended to follow and expand even further the previous editor's impressive efforts to have the journal reflect the diversity of its disciplinary community. Second, the editor also hopes to encourage innovative practitioners of the historiographic craft-especially digital researchers-to look to the journal as a friendly outlet. Third, in sympathy with APA's adoption of the Transparency and Openness Promotion (TOP) guidelines, the editor will work with authors to ensure that the sources of their historical claims are as clear as possible. Finally, please allow the editor to personally invite you, the reader, to assist me in supporting and enriching this journal. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
We investigate the contributions of fixed and mobile telecommunications (ICT) and mobile money to economic growth and financial inclusion in a 22-year panel of 146 countries. We extend the Solow ...growth model to include human capital, money, ICT, and mobile money, splitting the sample into sub-Saharan Africa (SSA) and the rest of the world (RoW) in addition to the whole sample analysis. We find mobile money affects economic growth through direct and indirect channels. Mobile money has a significant overall positive impact on growth, especially in countries with better mobile phone penetration and more dispersed populations. But its total quantitative effect is not large. Mobile money also tends to improve financial inclusion which in turn promotes growth. There are important differences between the SSA and RoW parameters, implying that the quantitative determinants of growth are different to some extent as between SSA and RoW.
•Mobile money has a positive effect on growth in Africa and elsewhere.•Mobile phone penetration also has a positive effect on growth in Africa.•Mobile money has a notably stronger effect in countries with dispersed populations.•Mobile money also promotes financial inclusion which in turn increases growth.•The growth effects differ in size as between Africa and rest of the world.
Admission of infants to hospital with bronchiolitis consumes considerable healthcare resources each winter. We report an analysis of hospital admissions in England over five decades.
Data were ...analysed from the Hospital In-Patient Enquiry (HIPE, 1968-1985), Hospital Episode Statistics (HES, 1989-2011), Oxford Record Linkage Study (ORLS, 1963-2011) and Paediatric Intensive Care Audit Network (PICANet, 2003-2012). Cases were identified using International Classification of Diseases (ICD) codes in discharge records. Bronchiolitis was given a separate code in ICD9 (used in England from 1979). Geographical variation was analysed using Local Authority area boundaries. Maternal and perinatal risk factors associated with bronchiolitis and subsequent admissions for asthma were analysed using record-linkage.
All-England HIPE and HES data recorded 468 138 episodes of admission for bronchiolitis in infants aged <1 year between 1979 and 2011. In 2011 the estimated annual hospital admission rate was 46.1 (95% CI 45.6 to 46.6) per 1000 infants aged <1 year. Between 2004 and 2011 the rates rose by an average of 1.8% per year in the all-England HES data, whereas admission rates to paediatric intensive care changed little (1.3 to 1.6 per 1000 infants aged <1 year). A fivefold geographical variation in hospital admission rates was observed. Young maternal age, low social class, low birth weight and maternal smoking were among factors associated with an increased risk of hospital admission with bronchiolitis.
Hospital admissions for infants with bronchiolitis have increased substantially in recent years. However, cases requiring intensive care have changed little since 2004.
Aquifer Thermal Energy Storage (ATES) uses excess thermal energy to heat water which is stored in an aquifer until it is needed, at which time the hot water is recovered and the heat used for some ...purpose e.g. electricity generation. The recovery efficiency (i.e. the ratio of heat energy recovered to heat energy injected, R) is one of the most important factors dictating the viability of ATES systems.
The variation of R with various aquifer properties and operating parameters is explored for high temperature (HT) ATES systems with injection temperatures ≥90∘C, extending the results of previous studies to higher temperatures and a broader range of aquifer properties and operating conditions. R values are calculated using numerical models of a single-well ATES system, which is validated by comparison with previous field and modelling studies.
The results show that HT-ATES may be viable with injection temperatures as high as 300 ∘C, depending on the aquifer properties and operating parameters. Daily cycles are very efficient over a broad range of conditions, whereas the efficiency of annual cycles is much more variable. The most important parameters governing R are aquifer thickness, injection temperature, horizontal and vertical permeability, and dispersion length.
The R values are used to derive an improved version of the Rayleigh number relationship proposed by Schout et al. (2014), extending the applicability of this relationship to daily cycles and improving its accuracy for annual cycles. An alternative method for estimating R using a convolutional neural network is proposed.
The calculated R values may be considered best-case because aspects such as background groundwater flow and geochemical effects are ignored. Practical factors such as energy supply/demand requirements, reservoir and above-ground engineering, financial or regulatory aspects, and public acceptance are not considered. Nevertheless, the results of this study can be used for rapid screening of large areas for potential HT-ATES sites, defining requirements for potential sites, and estimating R values for specific sites, before performing detailed feasibility studies.
•The recovery efficiency, R, of aquifer thermal energy storage systems is computed•A wide range of operating parameters are covered by the simulations•ATES may be viable up to 300 degC and daily cycles are very efficient•R is written in terms of the Rayleigh number; also a CNN is strongly predictive•R may be estimated accurately only when an accurate fluid equation of state is used
Standard treatment of poisoning by organophosphorus anticholinesterases uses atropine to reduce the muscarinic effects of acetylcholine accumulation and oximes to reactivate acetylcholinesterase (the ...effectiveness of which depends on the specific anticholinesterase), but does not directly address the nicotinic effects of poisoning. Bispyridinium molecules which act as noncompetitive antagonists at nicotinic acetylcholine receptors have been identified as promising compounds and one has been shown to improve survival following organophosphorus poisoning in guinea-pigs. Here, we have investigated the structural requirements for antagonism and compared inhibitory potency of these compounds at muscle and neuronal nicotinic receptors and acetylcholinesterase. A series of compounds was synthesised, in which the length of the polymethylene linker between the two pyridinium moieties was increased sequentially from one to ten carbon atoms. Their effects on nicotinic receptor-mediated calcium responses were tested in muscle-derived (CN21) and neuronal (SH-SY5Y) cells. Their ability to inhibit acetylcholinesterase activity was tested using human erythrocyte ghosts. In both cell lines, the nicotinic response was inhibited in a dose-dependent manner and the inhibitory potency of the compounds increased with greater linker length between the two pyridinium moieties, as did their inhibitory potency for human acetylcholinesterase activity in vitro. These results demonstrate that bispyridinium compounds inhibit both neuronal and muscle nicotinic receptors and that their potency depends on the length of the hydrocarbon chain linking the two pyridinium moieties. Knowledge of structure-activity relationships will aid the optimisation of molecular structures for therapeutic use against the nicotinic effects of organophosphorus poisoning.
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