Computation and analysis of evolutionary game dynamics

Biological processes are usually defined based on the principles of replication, mutation, competition, adaption, and evolution. In evolutionary game theory, such a process is modeled as a so-called evolutionary game, which not only provides an alternative interpretation of dynamical equilibrium in terms of the game nature of the process, but also bridges the stability of the biological process with the Nash equilibrium of the evolutionary game. Computationally, the evolutionary game models are described in terms of inverse and direct games, which are estimating the payoff matrix from data and computing the Nash equilibrium of a given payoff matrix respectively. We discuss the necessary and sufficient conditions for the Nash equilibrium states, and derive the methods for both inverse and direct games in this thesis. The inverse game is solved by a non-parametric smoothing method and penalized least squares method, while different schemes for the computation of the direct game are proposed including a specialized Snow-Shapley algorithm, a specialized Lemke-Howson algorithm, and an algorithm based on the solution of a complementarity problem on a simplex. Computation for the sparsest and densest Nash equilibria is investigated. We develop a new algorithm called dual method with better performance than the traditional Snow-Shapley method on the sparse and dense Nash equilibrium searching. Computational results are presented based on examples. The package incorporating all the schemes, the Toolbox of Evolution Dynamics Analysis (TEDA), is described

Simple parameter-free self-attention approximation

The hybrid model of self-attention and convolution is one of the methods to lighten ViT. The quadratic computational complexity of self-attention with respect to token length limits the efficiency of ViT on edge devices. We propose a self-attention approximation without training parameters, called SPSA, which captures global spatial features with linear complexity. To verify the effectiveness of SPSA combined with convolution, we conduct extensive experiments on image classification and object detection tasks

Non-neuronal cholinergic activity is potentiated in myasthenia gravis

Background: Non-neuronal acetylcholine (ACh) restricts autoimmune responses and attenuates inflammation by cholinergic anti-inflammation pathway. To date, the implication of ACh in myasthenia gravis (MG) remained unexplored. This study aimed to investigate the possible relationship between ACh levels, anti-muscle-specific tyrosine kinase (MuSK) antibody titers, main clinical features and outcomes of MG patients. Methods: We successfully measured ACh levels in human peripheral blood mononuclear cells (PBMCs) from 125 MG patients and 50 matched healthy controls by using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). We assessed the quantitative MG (QMG) scores for each patient and titered anti-MuSK antibody. Results: We found that PBMC-derived ACh level was significantly higher in MG patients, especially in patients of class III, IV-V, compared with that in controls (0.142 ± 0.108 vs. 0.075 ± 0.014 ng/million cells, p = 0.0003) according to the Myasthenia Gravis Foundation of America clinical classification. Importantly, we also found that ACh levels were positively correlated with QMG scores (r = 0.83, p \u3c 0.0001) and anti-MuSK Ab levels (r = 0.85, p \u3c 0.0001). Conclusions: Our demonstration of elevated ACh levels in PBMCs of MG patients foreshadows potential new avenues for MG research and treatment

Proteomics analysis of coronary blood microparticles in patients with acute myocardial infarction

Background: Acute myocardial infarction (AMI) is the leading cause of death for patients with cardiovascular disease (CVD). Although researchers have made substantial efforts to elucidate its pathogenesis, the molecular mechanisms underlying AMI remain unknown. The aim of this study was to use proteomics to identify differentially expressed proteins (DEPs) and the possible biological functions and metabolic pathways related to coronary blood microparticles (MPs) in patients with AMI and stable coronary artery disease (SCAD); this study will allow for the identification of individuals at risk of acute thrombosis. Methods: The study was performed on 5 AMI patients and 5 SCAD patients. DEPs were identified, and Gene Ontology (GO) enrichment and KEGG pathway enrichment analyses were performed to determine the relative abundance and biological function of the significant DEPs that were identified in the present study. Results: The current analysis identified 198 DEPs in the coronary blood of AMI patients and SCAD patients, including 85 proteins that were significantly upregulated and 113 proteins that were significantly downregulated. GO enrichment analysis demonstrated that GDP binding and GTP binding were enriched in molecular function. Similarly, KEGG pathway enrichment analysis revealed that the identified proteins were involved in pantothenate and coenzyme A biosynthesis, starch and sucrose metabolism, and the AMPK signalling pathway. Conclusions: The proteome of coronary MPs differs between patients with AMI and patients with SCAD. In summary, the GO terms and KEGG pathways enriched by the DEPs may reflect the possible molecular mechanisms underlying the pathogenesis of acute thrombosis in patients with AMI

Amino acid Formula induces Microbiota Dysbiosis and Depressive-Like Behavior in Mice

Amino acid formula (AAF) is increasingly consumed in infants with cow\u27s milk protein allergy; however, the long-term influences on health are less described. In this study, we established a mouse model by subjecting neonatal mice to an amino acid diet (AAD) to mimic the feeding regimen of infants on AAF. Surprisingly, AAD-fed mice exhibited dysbiotic microbiota and increased neuronal activity in both the intestine and brain, as well as gastrointestinal peristalsis disorders and depressive-like behavior. Furthermore, fecal microbiota transplantation from AAD-fed mice or AAF-fed infants to recipient mice led to elevated neuronal activations and exacerbated depressive-like behaviors compared to that from normal chow-fed mice or cow\u27s-milk-formula-fed infants, respectively. Our findings highlight the necessity to avoid the excessive use of AAF, which may influence the neuronal development and mental health of children

Contrasting male and female trends in tobacco-attributed mortality in China:evidence from successive nationwide prospective cohort studies

SummaryBackgroundChinese men now smoke more than a third of the world's cigarettes, following a large increase in urban then rural usage. Conversely, Chinese women now smoke far less than in previous generations. We assess the oppositely changing effects of tobacco on male and female mortality.MethodsTwo nationwide prospective studies 15 years apart recruited 220 000 men in about 1991 at ages 40–79 years (first study) and 210 000 men and 300 000 women in about 2006 at ages 35–74 years (second study), with follow-up during 1991–99 (mid-year 1995) and 2006–14 (mid-year 2010), respectively. Cox regression yielded sex-specific adjusted mortality rate ratios (RRs) comparing smokers (including any who had stopped because of illness, but not the other ex-smokers, who are described as having stopped by choice) versus never-smokers.FindingsTwo-thirds of the men smoked; there was little dependence of male smoking prevalence on age, but many smokers had not smoked cigarettes throughout adult life. Comparing men born before and since 1950, in the older generation, the age at which smoking had started was later and, particularly in rural areas, lifelong exclusive cigarette use was less common than in the younger generation. Comparing male mortality RRs in the first study (mid-year 1995) versus those in the second study (mid-year 2010), the proportional excess risk among smokers (RR-1) approximately doubled over this 15-year period (urban: RR 1·32 [95% CI 1·24–1·41] vs 1·65 [1·53–1·79]; rural: RR 1·13 [1·09–1·17] vs 1·22 [1·16–1·29]), as did the smoking-attributed fraction of deaths at ages 40–79 years (urban: 17% vs 26%; rural: 9% vs 14%). In the second study, urban male smokers who had started before age 20 years (which is now typical among both urban and rural young men) had twice the never-smoker mortality rate (RR 1·98, 1·79–2·19, approaching Western RRs), with substantial excess mortality from chronic obstructive pulmonary disease (COPD RR 9·09, 5·11–16·15), lung cancer (RR 3·78, 2·78–5·14), and ischaemic stroke or ischaemic heart disease (combined RR 2·03, 1·66–2·47). Ex-smokers who had stopped by choice (only 3% of ever-smokers in 1991, but 9% in 2006) had little smoking-attributed risk more than 10 years after stopping. Among Chinese women, however, there has been a tenfold intergenerational reduction in smoking uptake rates. In the second study, among women born in the 1930s, 1940s, 1950s, and since 1960 the proportions who had smoked were, respectively, 10%, 5%, 2%, and 1% (3097/30 943, 3265/62 246, 2339/97 344, and 1068/111 933). The smoker versus non-smoker RR of 1·51 (1·40–1·63) for all female mortality at ages 40–79 years accounted for 5%, 3%, 1%, and <1%, respectively, of all the female deaths in these four successive birth cohorts. In 2010, smoking caused about 1 million (840 000 male, 130 000 female) deaths in China.InterpretationSmoking will cause about 20% of all adult male deaths in China during the 2010s. The tobacco-attributed proportion is increasing in men, but low, and decreasing, in women. Although overall adult mortality rates are falling, as the adult population of China grows and the proportion of male deaths due to smoking increases, the annual number of deaths in China that are caused by tobacco will rise from about 1 million in 2010 to 2 million in 2030 and 3 million in 2050, unless there is widespread cessation.FundingWellcome Trust, MRC, BHF, CR-UK, Kadoorie Charitable Foundation, Chinese MoST and NSF

Ultrahigh-Frequency Surface Acoustic Wave Sensors with Giant Mass-Loading Effects on Electrodes

Surface acoustic wave (SAW) devices are widely used for physical, chemical, and biological sensing applications, and their sensing mechanisms are generally based on frequency changes due to mass-loading effects at the acoustic wave propagation area between two interdigitated transducers (IDTs). In this paper, a new sensing mechanism has been proposed based on a significantly enhanced mass-loading effect generated directly on Au IDT electrodes, which enables significantly enhanced sensitivity, compared with that of conventional SAW devices. The fabricated ultrahigh-frequency SAW devices show a significant mass-loading effect on the electrodes. When the Au-electrode thickness increased from 12 to 25 nm, the Rayleigh mode resonant frequency decreased from 7.77 to 5.93 GHz, while that of the higher longitudinal leaky SAW decreased from 11.87 to 9.83 GHz. The corresponding mass sensitivity of 7309 MHz·mm2·μg–1 (Rayleigh mode) is ∼8.9 × 1011 times larger than that of a conventional quartz crystal balance (with a frequency of 5 MHz) and ∼1000 times higher than that of conventional SAW devices (with a frequency of 978 MHz). Trinitrotoluene concentration as low as 4.4 × 10–9 M (mol·L–1) can be detected using the fabricated SAW sensor, proving its giant mass-loading effect and ultrahigh sensitivity

ALMA twenty-six arcmin2^2 survey of GOODS-S at one-millimeter (ASAGAO): Near-infrared-dark faint ALMA sources

We report detections of two 1.2 mm continuum sources ($S_\mathrm{1.2mm}$ ~ 0.6 mJy) without any counterparts in the deep $H$- and/or $K$-band image (i.e., $K$-band magnitude $\gtrsim$ 26 mag). These near-infrared-dark faint millimeter sources are uncovered by ASAGAO, a deep and wide-field ($\simeq$ 26 arcmin$^2$) Atacama Large Millimeter/submillimeter Array (ALMA) 1.2 mm survey. One has a red IRAC (3.6 and 4.5 $\mu$m) counterpart, and the other has been independently detected at 850 and 870 $\mu$m using SCUBA2 and ALMA Band 7, respectively. Their optical to radio spectral energy distributions indicate that they can lie at $z \gtrsim$ 3-5 and can be in the early phase of massive galaxy formation. Their contribution to the cosmic star formation rate density is estimated to be ~ 1 $\times$ 10$^{-3}$ $M_\odot$ yr$^{-1}$ Mpc$^{-3}$ if they lie somewhere in the redshift range of $z$ ~ 3-5. This value can be consistent with, or greater than that of bright submillimeter galaxies ($S_\mathrm{870\mu m}>$ 4.2 mJy) at $z$ ~ 3-5. We also uncover 3 more candidates near-infrared-dark faint ALMA sources without any counterparts ($S_\mathrm{1.2mm}$ ~ 0.45-0.86 mJy). These results show that an unbiased ALMA survey can reveal the dust-obscured star formation activities, which were missed in previous deep optical/near-infrared surveys.Comment: 10 pages, 6 figures, accepted for publication in Ap