Modeling and Simulation of Gas Emission Based on Recursive Modified Elman Neural Network

For the purpose of achieving more effective prediction of the absolute gas emission quantity, this paper puts forward a new model based on the hidden recurrent feedback Elman. The recursive part of classic Elman cannot be adjusted because it is fixed. To a certain extent, this drawback affects the approximation ability of the Elman, so this paper adds the correction factors in recursive part and uses the error feedback to determine the parameters. The stability of the recursive modified Elman neural network is proved in the sense of Lyapunov stability theory, and the optimal learning rate is given. With the historical data of mine actual monitoring to experiment and analysis, the results show that the recursive modified Elman neural network model can effectively predict the gas emission and improve the accuracy and efficiency of prediction compared with the classic Elman prediction model

HLA-DRB1 May Be Antagonistically Regulated by the Coordinately Evolved Promoter and 3′-UTR under Stabilizing Selection

HLA-DRB1 is the most polymorphic MHC (major histocompatibility complex) class II gene in human, and plays a crucial role in the development and function of the immune system. Extensive polymorphisms exist in the promoter and 3′-UTR of HLA-DRB1, especially a LTR (Long terminal repeat) element in the promoter, which may be involved in the expression regulation. However, it remains unknown how the polymorphisms in the whole promoter region and 3′-UTR to regulate the gene expression. In this study, we investigated the extensive polymorphisms in the HLA-DRB1 promoter and 3′-UTR, and how these polymorphisms affect the gene expression in both independent and jointly manners. It was observed that most of the haplotypes in the DRB1 promoter and 3′-UTR were clustered into 4 conserved lineages (H1, H2, H3 and H4), and showed high linkage disequilibrium. Compared with H1 and H2 lineage, a LTR element in the promoter of H3 and H4 lineage significantly suppressed the promoter activity, whereas the activity of the linked 3′-UTR increased, leading to no apparent difference in the final expression product between H1/H2 and H3/H4 lineage. Nevertheless, compared with the plasmid with a promoter and 3′-UTR from the same lineage, the recombinant plasmid with a promoter from H2 and a 3′-UTR from H3 showed about double fold increased luciferase activity, Conversely, the recombinant plasmid with a promoter from H3 and a 3′-UTR from H2 resulted in about 2-fold decreased luciferase activity. These results indicate that the promoter and 3′-UTR of HLA-DRB1 may antagonistically regulate the gene expression, which may be subjected to stabilizing selection. These findings may provide a novel insight into the mechanisms of the diseases associated with HLA-DRB1 genes

Prognostic Value of Choline and Betaine Depends on Intestinal Microbiota-Generated Metabolite Trimethylamine-N-Oxide

Aims: Recent metabolomics and animal model studies show trimethylamine-N-oxide (TMAO), an intestinal microbiota-dependent metabolite formed from dietary trimethylamine-containing nutrients such as phosphatidylcholine (PC), choline, and carnitine, is linked to coronary artery disease pathogenesis. Our aim was to examine the prognostic value of systemic choline and betaine levels in stable cardiac patients. Methods and Results: We examined the relationship between fasting plasma choline and betaine levels and risk of major adverse cardiac events (MACE = death, myocardial infraction, stroke) in relation to TMAO over 3 years of follow-up in 3903 sequential stable subjects undergoing elective diagnostic coronary angiography. In our study cohort, median (IQR) TMAO, choline, and betaine levels were 3.7 (2.4–6.2)μM, 9.8 (7.9–12.2)μM, and 41.1 (32.5–52.1)μM, respectively. Modest but statistically significant correlations were noted between TMAO and choline (r = 0.33, P \u3c 0.001) and less between TMAO and betaine (r = 0.09, P \u3c 0.001). Higher plasma choline and betaine levels were associated with a 1.9-fold and 1.4-fold increased risk of MACE, respectively (Quartiles 4 vs. 1; P \u3c 0.01, each). Following adjustments for traditional cardiovascular risk factors and high-sensitivity C-reactive protein, elevated choline [1.34 (1.03–1.74), P \u3c 0.05], and betaine levels [1.33 (1.03–1.73), P \u3c 0.05] each predicted increased MACE risk. Neither choline nor betaine predicted MACE risk when TMAO was added to the adjustment model, and choline and betaine predicted future risk for MACE only when TMAO was elevated. Conclusion: Elevated plasma levels of choline and betaine are each associated with incident MACE risk independent of traditional risk factors. However, high choline and betaine levels are only associated with higher risk of future MACE with concomitant increase in TMAO

Aberrant Dynamic Functional Connectivity of Posterior Cingulate Cortex Subregions in Major Depressive Disorder With Suicidal Ideation

Accumulating evidence indicates the presence of structural and functional abnormalities of the posterior cingulate cortex (PCC) in patients with major depressive disorder (MDD) with suicidal ideation (SI). Nevertheless, the subregional-level dynamic functional connectivity (dFC) of the PCC has not been investigated in MDD with SI. We therefore sought to investigate the presence of aberrant dFC variability in PCC subregions in MDD patients with SI. We analyzed resting-state functional magnetic resonance imaging (fMRI) data from 31 unmedicated MDD patients with SI (SI group), 56 unmedicated MDD patients without SI (NSI group), and 48 matched healthy control (HC) subjects. The sliding-window method was applied to characterize the whole-brain dFC of each PCC subregion [the ventral PCC (vPCC) and dorsal PCC (dPCC)]. In addition, we evaluated associations between clinical variables and the aberrant dFC variability of those brain regions showing significant between-group differences. Compared with HCS, the SI and the NSI groups exhibited higher dFC variability between the left dPCC and left fusiform gyrus and between the right vPCC and left inferior frontal gyrus (IFG). The SI group showed higher dFC variability between the left vPCC and left IFG than the NSI group. Furthermore, the dFC variability between the left vPCC and left IFG was positively correlated with Scale for Suicidal Ideation (SSI) score in patients with MDD (i.e., the SI and NSI groups). Our results indicate that aberrant dFC variability between the vPCC and IFG might provide a neural-network explanation for SI and may provide a potential target for future therapeutic interventions in MDD patients with SI

Gut Microbial Metabolite TMAO Enhances Platelet Hyperreactivity and Thrombosis Risk

Normal platelet function is critical to blood hemostasis and maintenance of a closed circulatory system. Heightened platelet reactivity, however, is associated with cardiometabolic diseases and enhanced potential for thrombotic events. We now show gut microbes, through generation of trimethylamine N-oxide (TMAO), directly contribute to platelet hyperreactivity and enhanced thrombosis potential. Plasma TMAO levels in subjects (n \u3e 4,000) independently predicted incident (3 years) thrombosis (heart attack, stroke) risk. Direct exposure of platelets to TMAO enhanced sub-maximal stimulus-dependent platelet activation from multiple agonists through augmented Ca2+ release from intracellular stores. Animal model studies employing dietary choline or TMAO, germ-free mice, and microbial transplantation collectively confirm a role for gut microbiota and TMAO in modulating platelet hyperresponsiveness and thrombosis potential and identify microbial taxa associated with plasma TMAO and thrombosis potential. Collectively, the present results reveal a previously unrecognized mechanistic link between specific dietary nutrients, gut microbes, platelet function, and thrombosis risk

A nanobody-based molecular toolkit for ubiquitin–proteasome system explores the main role of survivin subcellular localization

Targeted protein degradation is a powerful tool for determining the function of specific proteins nowadays. Survivin is the smallest member of the inhibitor of the apoptosis protein (IAP) family. It exists in the cytoplasm and nucleus of cells, but the exact function of survivin in different subcellular locations retained unclear updates due to the lack of effective and simple technical means. In this study, we created a novel nanoantibody-based molecular toolkit, namely, the ubiquitin–proteasome system (Nb4A-Fc-T2A-TRIM21), that can target to degrade survivin localized in cytoplasmic and cell nuclear by ubiquitinating, and by which to verify the potential roles of survivin subcellular localization. Also, the results showed that the cytoplasmic survivin mainly plays an anti-apoptotic function by directly or indirectly inhibiting the caspase pathway, and the nuclear survivin mainly promotes cell proliferation and participates in the regulation of the cell cycle. In addition, the Nb4A-Fc-T2A-TRIM21 system can degrade the endogenous survivin protein in a large amount by the ubiquitin–proteasome pathway, and the system can provide theoretical support for ubiquitination degradation targeting other endogenous proteins

Potential Application of MicroRNA Profiling to the Diagnosis and Prognosis of HIV-1 Infection

MicroRNAs (miRNAs) were first identified in Caenorhabditis briggsae and later recognized as playing pivotal roles in a vast range of cellular activities. It has been shown that miRNAs are an important mechanism not only for host defense against virus but also for the establishment of viral infection. During human immunodeficiency virus type 1 (HIV-1) infection, host miRNA profiles are altered either as a host response against the virus or alternatively as a mechanism for the virus to facilitate viral replication and infection or to maintain latency. The altered miRNA profiles can be detected and quantified by various advanced assays, and potentially serve as more sensitive, accurate and cost-efficient biomarkers for HIV-1 diagnosis and disease progression than those detected by currently available standard clinical assays. Such new biomarkers are critical for optimizing treatment regimens. In this review, we focus on the potential application of miRNA profiling to the diagnosis of HIV-1 infection and the monitoring of disease progression

Linking lidar multiple scattering profiles to snow depth and snow density: an analytical radiative transfer analysis and the implications for remote sensing of snow

Lidar multiple scattering measurements provide the probability distribution of the distance laser light travels inside snow. Based on an analytic two-stream radiative transfer solution, the present study demonstrates why/how these lidar measurements can be used to derive snow depth and snow density. In particular, for a laser wavelength with little snow absorption, an analytical radiative transfer solution is leveraged to prove that the physical snow depth is half of the average distance photons travel inside snow and that the relationship linking lidar measurements and the extinction coefficient of the snow is valid. Theoretical formulas that link lidar measurements to the extinction coefficient and the effective grain size of snow are provided. Snow density can also be derived from the multi-wavelength lidar measurements of the snow extinction coefficient and snow effective grain size. Alternatively, lidars can provide the most direct snow density measurements and the effective discrimination between snow and trees by adding vibrational Raman scattering channels

An Abundant Dysfunctional Apolipoprotein A1 in Human Atheroma

Recent studies have indicated that high-density lipoproteins (HDLs) and their major structural protein, apolipoprotein A1 (apoA1), recovered from human atheroma are dysfunctional and are extensively oxidized by myeloperoxidase (MPO). In vitro oxidation of either apoA1 or HDL particles by MPO impairs their cholesterol acceptor function. Here, using phage display affinity maturation, we developed a high-affinity monoclonal antibody that specifically recognizes both apoA1 and HDL that have been modified by the MPO-H2O2-Cl− system. An oxindolyl alanine (2-OH-Trp) moiety at Trp72 of apoA1 is the immunogenic epitope. Mutagenesis studies confirmed a critical role for apoA1 Trp72 in MPO-mediated inhibition of the ATP-binding cassette transporter A1 (ABCA1)-dependent cholesterol acceptor activity of apoA1 in vitro and in vivo. ApoA1 containing a 2-OH-Trp72 group (oxTrp72-apoA1) is in low abundance within the circulation but accounts for 20% of the apoA1 in atherosclerosis-laden arteries. OxTrp72-apoA1 recovered from human atheroma or plasma is lipid poor, virtually devoid of cholesterol acceptor activity and demonstrated both a potent proinflammatory activity on endothelial cells and an impaired HDL biogenesis activity in vivo. Elevated oxTrp72-apoA1 levels in subjects presenting to a cardiology clinic (n = 627) were associated with increased cardiovascular disease risk. Circulating oxTrp72-apoA1 levels may serve as a way to monitor a proatherogenic process in the artery wall