Homeostatic proliferation generates long-lived natural killer cells that respond against viral infection

Like memory T cells, natural killer cells that undergo homeostatic expansion in mice self-renew and retain the ability to respond to subsequent viral infection

BioSimulators: a central registry of simulation engines and services for recommending specific tools

Computational models have great potential to accelerate bioscience, bioengineering, and medicine. However, it remains challenging to reproduce and reuse simulations, in part, because the numerous formats and methods for simulating various subsystems and scales remain siloed by different software tools. For example, each tool must be executed through a distinct interface. To help investigators find and use simulation tools, we developed BioSimulators (https://biosimulators.org), a central registry of the capabilities of simulation tools and consistent Python, command-line and containerized interfaces to each version of each tool. The foundation of BioSimulators is standards, such as CellML, SBML, SED-ML and the COMBINE archive format, and validation tools for simulation projects and simulation tools that ensure these standards are used consistently. To help modelers find tools for particular projects, we have also used the registry to develop recommendation services. We anticipate that BioSimulators will help modelers exchange, reproduce, and combine simulations

The International Role of the Dollar: Does It Matter if This Changes?

There is often speculation that the international roles of currencies may be changing. This paper presents the current status of these roles. The U.S. dollar continues to be the dominant currency across various uses. Yet, such a role may change over time. If this occurs, there could be consequences for seignorage returns, U.S. funding costs, the dollar's value, U.S. insulation from foreign shocks, and U.S. global influence. The paper concludes with a discussion of recent research on related themes and questions for future study

Machine learning approaches for large scale classification of produce

Abstract The analysis and identification of different attributes of produce such as taxonomy, vendor, and organic nature is vital to verifying product authenticity in a distribution network. Though a variety of analysis techniques have been studied in the past, we present a novel data-centric approach to classifying produce attributes. We employed visible and near infrared (NIR) spectroscopy on over 75,000 samples across several fruit and vegetable varieties. This yielded 0.90–0.98 and 0.98–0.99 classification accuracies for taxonomy and farmer classes, respectively. The most significant factors in the visible spectrum were variations in the produce color due to chlorophyll and anthocyanins. In the infrared spectrum, we observed that the varying water and sugar content levels were critical to obtaining high classification accuracies. High quality spectral data along with an optimal tuning of hyperparameters in the support vector machine (SVM) was also key to achieving high classification accuracies. In addition to demonstrating exceptional accuracies on test data, we explored insights behind the classifications, and identified the highest performing approaches using cross validation. We presented data collection guidelines, experimental design parameters, and machine learning optimization parameters for the replication of studies involving large sample sizes

Calorie restriction does not increase short-term or long-term protein synthesis

Increased protein synthesis is proposed as a mechanism of life-span extension during caloric restriction (CR). We hypothesized that CR does not increase protein synthesis in all tissues and protein fractions and that any increased protein synthesis with CR would be due to an increased anabolic effect of feeding. We used short- (4 hours) and long-term (6 weeks) methods to measure in vivo protein synthesis in lifelong ad libitum (AL) and CR mice. We did not detect an acute effect of feeding on protein synthesis while liver mitochondrial protein synthesis was lower in CR mice versus AL mice. Mammalian target of rapamycin (mTOR) signaling was repressed in liver and heart from CR mice indicative of energetic stress and suppression of growth. Our main findings were that CR did not increase rates of mixed protein synthesis over the long term or in response to acute feeding, and protein synthesis was maintained despite decreased mTOR signaling

Estimating the contribution of CD4 T cell subset proliferation and differentiation to HIV persistence

Persistence of HIV in people living with HIV (PWH) on suppressive antiretroviral therapy (ART) has been linked to physiological mechanisms of CD4+ T cells. Here, in the same 37 male PWH on ART we measure longitudinal kinetics of HIV DNA and cell turnover rates in five CD4 cell subsets: naïve (TN), stem-cell- (TSCM), central- (TCM), transitional- (TTM), and effector-memory (TEM). HIV decreases in TTM and TEM but not in less-differentiated subsets. Cell turnover is ~10 times faster than HIV clearance in memory subsets, implying that cellular proliferation consistently creates HIV DNA. The optimal mathematical model for these integrated data sets posits HIV DNA also passages between CD4 cell subsets via cellular differentiation. Estimates are heterogeneous, but in an average participant's year ~10 (in TN and TSCM) and ~104 (in TCM, TTM, TEM) proviruses are generated by proliferation while ~103 proviruses passage via cell differentiation (per million CD4). In simulations, therapies blocking proliferation and/or enhancing differentiation could reduce HIV DNA by 1-2 logs over 3 years. In summary, HIV exploits cellular proliferation and differentiation to persist during ART but clears faster in more proliferative/differentiated CD4 cell subsets and the same physiological mechanisms sustaining HIV might be temporarily modified to reduce it

Immigration: The European Experience

This paper first presents a brief historical overview of immigration in Europe. We then provide (and distinguishing between EU and non-EU immigrants) a comprehensive analysis of the skill structures of immigrants and their labor market integration in the different European countries, their position in the wage distribution, and the situation of their children, and discuss the disadvantage of immigrants and their children relative to natives. We show that immigrants - in particular those from non-EU countries - are severely disadvantaged in most countries, even if we compare them to natives with the same measurable skills. We conclude with a discussion of the role of regulations and institutions as one possible mechanism for these findings, and suggest directions for future research

Liquid chromatography–high resolution mass spectrometry analysis of fatty acid metabolism

We present a liquid chromatography/mass spectrometry (LC/MS) method for long-chain and very-long-chain fatty acid analysis and its application to 13C-tracer studies of fatty acid metabolism. Fatty acids containing 14 to 36 carbon atoms are separated by C8 reversed-phase chromatography using a water–methanol gradient with tributylamine as ion pairing agent, ionized by electrospray and analyzed by a stand-alone orbitrap mass spectrometer. The median limit of detection is 5 ng/mL with a linear dynamic range of 100-fold. Ratios of unlabeled to 13C-labeled species are quantitated precisely and accurately (average relative standard deviation 3.2% and deviation from expectation 2.3%). In samples consisting of fatty acids saponified from cultured mammalian cells, 45 species are quantified, with average intraday relative standard deviations for independent biological replicates of 11%. The method enables quantitation of molecular ion peaks for all labeled forms of each fatty acid. Different degrees of 13C-labeling from glucose and glutamine correspond to fatty acid uptake from media, de novo synthesis, and elongation. To exemplify the utility of the method, we examined isogenic cell lines with and without activated Ras oncogene expression. Ras increases the abundance and alters the labeling patterns of saturated and monounsaturated very-long-chain fatty acids, with the observed pattern consistent with Ras leading to enhanced activity of ELOVL4 or an enzyme with similar catalytic activity. This LC/MS method and associated isotope tracer techniques should be broadly applicable to investigating fatty acid metabolism