Variability and Spectral Behavior of Gamma-ray Flares of 3C 279

3C 279 showed enhanced flux variations in Fermi-LAT {\gamma}-ray observations from January to June 2018. We present a detailed Fermi-LAT analysis to investigate the variability and spectral behaviors of 3C 279 during the {\gamma}-ray flares in 2018. In this work, we analyzed the {\gamma}-ray spectra and found that the spectra in either the flaring or quiescent states do not show any clear breaks (or cutoffs). This indicates that the dissipation region is outside the broad-line region, and the energy dissipation may be due to the inverse Compton process of scattering the dust torus infrared photons, this result is also consistent with that in Tolamatti et al. An external inverse Compton scattering of dusty torus (DT) photons is employed to calculate the broadband spectral energy distribution (SED). This model was further supported by the fact that we found flare decay timescale was consistent with the cooling time of relativistic electrons through DT photons. During the SED modeling, a relatively harder spectrum for the electron energy distribution (EED) is found and suggests these electrons may not be accelerated by the shock that happened in the dissipation region. Besides, the magnetic reconnection is also ruled out due to a low magnetization ratio. Thus, we suggest an injection of higher-energy electrons from outside the blob and raising the flare.Comment: 12 pages, 6 figures, published in the Publications of the Astronomical Society of the Pacifi

Is I-Voting I-Llegal?

The Voting Rights Act was passed to prevent racial discrimination in all voting booths. Does the existence of a racial digital divide make Internet elections for public office merely a computer geek\u27s pipe dream? Or can i-voting withstand scrutiny under the current state of the law? This i-Brief will consider the current state of the law, and whether disproportionate benefits will be enough to stop this extension of technology dead in its tracks

Doppler Factor Estimation for Fermi Blazars

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The importance of NOx control for peak ozone mitigation based on a sensitivity study using CMAQ‐HDDM‐3D model during a typical episode over the Yangtze River delta region, China.

In recent years, ground-level ozone (O3) has been one of the main pollutants hindering air quality compliance in China's large city-clusters including the Yangtze River Delta (YRD) region. In this work, we utilized the process analysis (PA) and the higher-order decoupled direct method (HDDM-3D) tools embedded in the Community Multiscale Air Quality model (CMAQ) to characterize O3 formation and sensitivities to precursors during a typical O3 pollution episode over the YRD region in July 2018. Results indicate that gas-phase chemistry contributed dominantly to the ground-level O3 although a significant proportion was chemically produced at the middle and upper boundary layer before reaching the surface via diffusion process. Further analysis of the chemical pathways of O3 and Ox formation provided deep insights into the sensitivities of O3 to its precursors that were consistent with the HDDM results. The first-order sensitivities of O3 to anthropogenic volatile organic compounds (AVOC) were mainly positive but small, and temporal variations were negligible compared with those to NOx. During the peak O3 time in the afternoon, the first- and second-order sensitivities of O3 to NOx were significantly positive and negative, respectively, suggesting a convex response of O3 to NOx over most areas including Shanghai, Hangzhou, Nanjing and Hefei. These findings further highlighted an accelerated decrease in ground-level O3 in the afternoon corresponding to continuous decrease of NOx emissions in the afternoon. Therefore, over the YRD region including its metropolises, NOx emission reductions will be more important in reducing the afternoon peak O3 concentration compared with the effect of VOC emission control alone

Experimental impacts of grazing on grassland biodiversity and function are explained by aridity

Grazing by domestic herbivores is the most widespread land use on the planet, and also a major global change driver in grasslands. Yet, experimental evidence on the long-term impacts of livestock grazing on biodiversity and function is largely lacking. Here, we report results from a network of 10 experimental sites from paired grazed and ungrazed grasslands across an aridity gradient, including some of the largest remaining native grasslands on the planet. We show that aridity partly explains the responses of biodiversity and multifunctionality to long-term livestock grazing. Grazing greatly reduced biodiversity and multifunctionality in steppes with higher aridity, while had no effects in steppes with relatively lower aridity. Moreover, we found that long-term grazing further changed the capacity of above- and below-ground biodiversity to explain multifunctionality. Thus, while plant diversity was positively correlated with multifunctionality across grasslands with excluded livestock, soil biodiversity was positively correlated with multifunctionality across grazed grasslands. Together, our cross-site experiment reveals that the impacts of long-term grazing on biodiversity and function depend on aridity levels, with the more arid sites experiencing more negative impacts on biodiversity and ecosystem multifunctionality. We also highlight the fundamental importance of conserving soil biodiversity for protecting multifunctionality in widespread grazed grasslands

Identification and validation of oxidative stress and immune-related hub genes in Alzheimer’s disease through bioinformatics analysis

Abstract Alzheimer’s disease (AD) is the leading cause of dementia in aged population. Oxidative stress and neuroinflammation play important roles in the pathogenesis of AD. Investigation of hub genes for the development of potential therapeutic targets and candidate biomarkers is warranted. The differentially expressed genes (DEGs) in AD were screened in GSE48350 dataset. The differentially expressed oxidative stress genes (DEOSGs) were analyzed by intersection of DEGs and oxidative stress-related genes. The immune-related DEOSGs and hub genes were identified by weighted gene co-expression network analysis (WGCNA) and protein–protein interaction (PPI) analysis, respectively. Enrichment analysis was performed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. The diagnostic value of hub genes was assessed by receiver operating characteristic analysis and validated in GSE1297. The mRNA expression of diagnostic genes was determined by qRT-PCR analysis. Finally, we constructed the drug, transcription factors (TFs), and microRNA network of the diagnostic genes. A total of 1160 DEGs (259 up-regulated and 901 down-regulated) were screened in GSE48350. Among them 111 DEOSGs were identified in AD. Thereafter, we identified significant difference of infiltrated immune cells (effector memory CD8 T cell, activated B cell, memory B cell, natural killer cell, CD56 bright natural killer cell, natural killer T cell, plasmacytoid dendritic cell, and neutrophil) between AD and control samples. 27 gene modules were obtained through WGCNA and turquoise module was the most relevant module. We obtained 66 immune-related DEOSGs by intersecting turquoise module with the DEOSGs and identified 15 hub genes through PPI analysis. Among them, 9 hub genes (CCK, CNR1, GAD1, GAP43, NEFL, NPY, PENK, SST, and TAC1) were identified with good diagnostic values and verified in GSE1297. qRT-PCR analysis revealed the downregulation of SST, NPY, GAP43, CCK, and PENK and upregulation of NEFL in AD. Finally, we identified 76 therapeutic agents, 152 miRNAs targets, and 91 TFs regulatory networks. Our study identified 9 key genes associated with oxidative stress and immune reaction in AD pathogenesis. The findings may help to provide promising candidate biomarkers and therapeutic targets for AD

Integrated analysis of C3AR1 and CD163 associated with immune infiltration in intracranial aneurysms pathogenesis

Background: To identify potential immune-related biomarkers, molecular mechanism, and therapeutic agents of intracranial aneurysms (IAs). Methods: We identified the differentially expressed genes (DEGs) between IAs and control samples from GSE75436, GSE26969, GSE6551, and GSE13353 datasets. We used weighted gene co-expression network analysis (WGCNA) and protein–protein interaction (PPI) analysis to identify immune-related hub genes. We evaluated the expression of hub genes by using qRT-PCR analysis. Using miRNet, NetworkAnalyst, and DGIdb databases, we analyzed the regulatory networks and potential therapeutic agents targeting hub genes. Least absolute shrinkage and selection operator (LASSO) logistic regression was performed to identify optimal biomarkers among hub genes. The diagnostic value was validated by external GSE15629 dataset. Results: We identified 227 DEGs and 22 differentially infiltrating immune cells between IAs and control samples from GSE75436, GSE26969, GSE6551, and GSE13353 datasets. We further identified 41 differentially expressed immune-related genes (DEIRGs), which were primarily enriched in the chemokine-mediated signaling pathway, myeloid leukocyte migration, endocytic vesicle membrane, chemokine receptor binding, chemokine activity, and viral protein interactions with cytokines and their receptors. Among 41 DEIRGs, 10 hub genes including C3AR1, CD163, CCL4, CXCL8, CCL3, TLR2, TYROBP, C1QB, FCGR3A, and FCGR1A were identified with good diagnostic values (AUC >0.7). Hsa-mir-27a-3p and transcription factors, including YY1 and GATA2, were identified the primary regulators of hub genes. 92 potential therapeutic agents targeting hub genes were predicted. C3AR1 and CD163 were finally identified as the best diagnostic biomarkers using LASSO logistic regression (AUC = 0.994). The diagnostic value of C3AR1 and CD163 was validated by the external GSE15629 dataset (AUC = 0.914). Conclusions: This study revealed the importance of C3AR1 and CD163 in immune infiltration in IAs pathogenesis. Our finding provided a valuable reference for subsequent research on the potential targets for molecular mechanisms and intervention of IAs

RAD001 (everolimus) attenuates experimental autoimmune neuritis by inhibiting the mTOR pathway, elevating Akt activity and polarizing M2 macrophages

AbstractGuillain–Barre' syndrome (GBS) is an acute, postinfectious, immune-mediated, demyelinating disease of peripheral nerves and nerve roots. As a classical animal model of GBS, experimental autoimmune neuritis (EAN) has become well-accepted. Additionally, the potent immune modulation exerted by mammalian target of rapamycin (mTOR) inhibitors has been used to treat cancers and showed beneficial effects. Here we demonstrate that the mTOR inhibitor RAD001 (everolimus) protected rats from the symptoms of EAN, as shown by decreased paralysis, diminished inflammatory cell infiltration, reductions in demyelination of peripheral nerves and improved nerve conduction. Furthermore, RAD001 shifted macrophage polarization toward the protective M2 phenotype and modified the inflammatory milieu by downregulating the production of pro-inflammatory cytokines including IFN-γ and IL-17as well as upregulating the release of anti-inflammatory cytokines such as IL-4 and TGF-β. Amounts of the mTOR downstream targets p-P70S6K and p-4E-BP1 in sciatic nerves decreased, whereas the level of its upstream protein p-Akt was elevated. This demonstrated that RAD001 inhibited the mTOR pathway and encouraged the expression of p-Akt, which led to M2 macrophage polarization, thus improved the outcome of EAN in rats. Consequently, RAD001 exhibits strong potential as a therapeutic strategy for ameliorating peripheral poly-neuropathy

Additional file 1: Figure S1. of Dimethyl fumarate attenuates experimental autoimmune neuritis through the nuclear factor erythroid-derived 2-related factor 2/hemoxygenase-1 pathway by altering the balance of M1/M2 macrophages

DMF promotes M2 macrophage polarization in EAN. DMF was administered orally to EAN rats (n = 6 in each group) from day 1 to day 16 or day 7 to day 16 post-immunization for preventative or therapeutic treatment, respectively. On day 16 post-immunization, sciatic nerves of each group of rats were harvested for fluorescence immunohistochemistry to analyze the proportion of M1 macrophages and M2 macrophages in EAN rats after DMF treatment paradigms. (A) Fluorescence photomicrographs showing M1 and M2 macrophages in the sciatic nerves of EAN rats. Tissue sections were immunofluorescence stained for markers iNOS of M1, Arg1 of M2 macrophages, and Iba1 of general macrophages as indicated. Scale bar is 50 μm. (B) Quantitation of immunohistochemistry. Counts per square millimeter of Iba1+/iNOS+ cells (M1 phenotype) in the sciatic nerve showed that DMF reduced the number of M1 macrophages in both DMF treatment paradigms. (C) Counts per square millimeter of Iba1+/Arg1+ cells (M2 phenotype) showed that DMF-treated groups increased the number of M2 macrophages in both DMF treatment paradigms compared to the CMC group (p < 0.05). (DOCX 399 kb