Diagnosing ocean feedbacks to the BSISO: SST-modulated surface fluxes and the moist static energy budget

The oceanic feedback to the atmospheric boreal summer intraseasonal oscillation (BSISO) is examined by diagnosing the sea surface temperature (SST) modification of surface fluxes and the moist static energy (MSE) on intraseasonal scales. SST variability affects intraseasonal surface latent heat (LH) and sensible heat (SH) fluxes, through its influence on air-sea moisture and temperature gradients (delta-q and delta-T). According to bulk formula decomposition, LH is mainly determined by wind-driven flux perturbations, while SH is more sensitive to thermodynamic flux perturbations. SST fluctuations tend to increase the thermodynamic flux perturbations over active BSISO regions, but this is largely offset by the wind-driven flux perturbations. Enhanced surface fluxes induced by intraseasonal SST anomalies are located ahead (north) of the convective center over both the Indian Ocean and western Pacific, favoring BSISO northward propagation. Analysis of budgets of column-integrated MSE () and its time rate of change (d/dt) show that SST-modulated surface fluxes can influence the development and propagation of the BSISO, respectively. LH and SH variability induced by intraseasonal SSTs maintain 1-2% of /day over the equatorial western Indian Ocean, Arabian Sea and Bay of Bengal, but damp about 1% of /day over the western North Pacific. The contribution of intraseasonal SST variability to d/dt can reach 12-20% over active BSISO regions. These results suggest that SST variability is conducive, but perhaps not essential, for the propagation of convection during the BSISO life cycle

Efficient Graph Neural Network Inference at Large Scale

Graph neural networks (GNNs) have demonstrated excellent performance in a wide range of applications. However, the enormous size of large-scale graphs hinders their applications under real-time inference scenarios. Although existing scalable GNNs leverage linear propagation to preprocess the features and accelerate the training and inference procedure, these methods still suffer from scalability issues when making inferences on unseen nodes, as the feature preprocessing requires the graph is known and fixed. To speed up the inference in the inductive setting, we propose a novel adaptive propagation order approach that generates the personalized propagation order for each node based on its topological information. This could successfully avoid the redundant computation of feature propagation. Moreover, the trade-off between accuracy and inference latency can be flexibly controlled by simple hyper-parameters to match different latency constraints of application scenarios. To compensate for the potential inference accuracy loss, we further propose Inception Distillation to exploit the multi scale reception information and improve the inference performance. Extensive experiments are conducted on four public datasets with different scales and characteristics, and the experimental results show that our proposed inference acceleration framework outperforms the SOTA graph inference acceleration baselines in terms of both accuracy and efficiency. In particular, the advantage of our proposed method is more significant on larger-scale datasets, and our framework achieves $75\times$ inference speedup on the largest Ogbn-products dataset

The convection connection: how ocean feedbacks affect tropical mean moisture and MJO propagation

The response of the Madden-Julian oscillation (MJO) to ocean feedbacks is studied with coupled and uncoupled simulations of four general circulation models (GCMs). Monthly mean SST from each coupled model is prescribed to its respective uncoupled simulation, to ensure identical SST mean state and low-frequency variability between simulation pairs. Consistent with previous studies, coupling improves each model's ability to propagation MJO convection beyond the Maritime Continent. Analysis of the MJO moist static energy budget reveals that improved MJO eastward propagation in all four coupled models arises from enhanced meridional advection of column water vapor (CWV). Despite the identical mean state SST in each coupled and uncoupled simulation pair, coupling increases mean-state CWV near the Equator, sharpening equatorial moisture gradients and enhancing meridional moisture advection and MJO propagation. CWV composites during MJO and non-MJO periods demonstrate that the MJO itself does not cause enhanced moisture gradients. Instead, analysis of low-level subgrid-scale moistening conditioned by rainfall rate (R) and SST anomaly reveals that coupling enhances low-level convective moistening for R > 5 mm/day; this enhancement is most prominent near the Equator. The low-level moistening process varies among the four models, which we interpret in terms of their ocean model configurations, cumulus parameterizations, and the sensitivity of convection to column relative humidity

Boreal summer intraseasonal oscillation in a superparameterized general circulation model: effects of air–sea coupling and ocean mean state

The effect of air-sea coupling on the simulated boreal summer intraseasonal oscillation (BSISO) is examined using atmosphere--ocean-mixed-layer coupled (SPCAM3-KPP) and uncoupled configurations of the superparameterized (SP) Community Atmospheric Model, version 3 (SPCAM3). The coupled configuration is constrained to either observed ocean mean state or the mean state from the SP coupled configuration with a dynamic ocean (SPCCSM), to understand the effect of mean-state biases on the BSISO. All configurations overestimate summer mean subtropical rainfall and its intraseasonal variance. All configurations simulate realistic BSISO northward propagation over the Indian Ocean and western Pacific, in common with other SP configurations. Prescribing the 31-day smoothed sea-surface temperature (SST) from the SPCAM3-KPP simulation in SPCAm3 worsens the overestimated BSISO variance. In both coupled models, the phase relationship between intraseasonal rainfall and SST is well captured. This suggests that air-sea coupling improves the amplitude of the simulated BSISO and contributes to the propagation of convection. Constraining SPCAM3-KPP to the SPCCSM3 mean state also reduces the overestimated BSISO variability, but weakens BSISO propagation. Using the SPCCSM3 mean state also introduces a one-month delay to the BSISO seasonal cycle compared to SPCAM3-KPP with the observed ocean mean state, which matches well with observations. Based on a Taylor diagram, both air-sea coupling and SPCCSM3 mean state SST biases generally lead to higher simulated BSISO fidelity, largely due to their abilities to suppress the overestimated subtropical BSISO variance

México: informe de la coyuntura económica: primer trimestre de 1999

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Comparative transcriptome analysis of PBMC from HIV patients pre- and post-antiretroviral therapy

Infections of the human immunodeficiency virus (HIV) trigger host immune responses, but the virus can destroy the immune system and cause acquired immune deficiency syndrome (AIDS). Highly active antiretroviral therapy (HAART) can suppress viral replication and restore the impaired immune function. To understand HIV interactions with host immune cells during HAART, the transcriptomes of peripheral blood mononuclear cells (PBMC) from HIV patients and HIV negative volunteers before and two weeks after HAART initiation were analyzed using RNA sequencing (RNA-Seq) technology. Differentially expressed genes (DEGs) in response to HAART were firstly identified for each individual, then common features were extracted by comparing DEGs among individuals and finally HIV-related DEGs were obtained by comparing DEGs between the HIV patients and HIV negative volunteers. To demonstrate the power of this approach, minimum numbers of patients (one HIV alone; one HIV + tuberculosis, TB; one HIV + TB with immune reconstitution inflammatory syndrome during HAART) and two HIV negative volunteers were used. More than 15,000 gene transcripts were detected in each individual sample. Fourteen HAART up-regulated and eleven down-regulated DEGs were specifically identified in the HIV patients. Among them, nine up-regulated (CXCL1, S100P, AQP9, BASP1, MMP9, SOD2, LIMK2, IL1R2 and BCL2A1) and nine down-regulated DEGs (CD160, CD244, CX3CR1, IFIT1, IFI27, IFI44, IFI44L, MX1 and SIGLEC1) have already been reported as relevant to HIV infections in the literature, which demonstrates the credibility of the method. The newly identified HIV-related genes (up-regulated: ACSL1, GPR84, GPR97, ADM, LRG1; down-regulated: RASSF1, PATL2) were empirically validated using qRT-PCR. The Gene Set Enrichment Analysis (GSEA) was also used to determine pathways significantly affected by HAART. GSEA further confirmed the HAART relevance of five genes (ADM, AQP9, BASP1, IL1R2 and MMP9). The newly identified HIV-related genes, ADM (which encodes Adrenomedullin), a peptide hormone in circulation control, may contribute to HIV-associated hypertensions, providing new insights into HIV pathology and novel strategies for developing anti-HIV target. More importantly, we demonstrated that comparative transcriptome analysis is a very powerful tool to identify infection related DEGs using a very small number of samples. This approach could be easily applied to improve the understanding of pathogen-host interactions in many infections and anti-infection treatments

Antibacterial activity of the novel oxazolidinone contezolid (MRX-I) against Mycobacterium abscessus

ObjectiveTo evaluate contezolid (MRX-I) antibacterial activity against Mycobacterium abscessus in vitro and in vivo and to assess whether MRX-I treatment can prolong survival of infected zebrafish.MethodsMRX-I inhibitory activity against M. abscessus in vitro was assessed by injecting MRX-I into zebrafish infected with green fluorescent protein-labelled M. abscessus. Thereafter, infected zebrafish were treated with azithromycin (AZM), linezolid (LZD) or MRX-I then maximum tolerated concentrations (MTCs) of drugs were determined based on M. abscessus growth inhibition using one-way ANOVA. Linear trend analysis of CFU counts and fluorescence intensities (mean ± SE values) was performed to detect linear relationships between MRX-I, AZM and LZD concentrations and these parameters.ResultsMRX-I anti-M. abscessus minimum inhibitory concentration (MIC) and MTC were 16 μg/mL and 15.6 μg/mL, respectively. MRX-I MTC-treated zebrafish fluorescence intensities were significantly lower than respective LZD group intensities (whole-body: 439040 ± 3647 vs. 509184 ± 23064, p < 0.01); head: 74147 ± 2175 vs. 95996 ± 8054, p < 0.05). As MRX-I concentration was increased from 0.488 μg/mL to 15.6 μg/mL, zebrafish whole-body, head and heart fluorescence intensities decreased. Statistically insignificant differences between the MRX-I MTC group survival rate (78.33%) vs. corresponding rates of the 62.5 μg/mL-treated AZM MTC group (88.33%, p > 0.05) and the 15.6 μg/mL-treated LZD MTC group (76.67%, p > 0.05) were observed.ConclusionMRX-I effectively inhibited M. abscessus growth and prolonged zebrafish survival when administered to M. abscessus-infected zebrafish, thus demonstrating that MRX-I holds promise as a clinical treatment for human M. abscessus infections

Antibacterial activity of the novel compound Sudapyridine (WX-081) against Mycobacterium abscessus

ObjectiveThis study aimed to investigate sudapyridine (WX-081) antibacterial activity against Mycobacterium abscessus in vitro and its effect on in vivo bacterial growth and host survival using a zebrafish model of M. abscessus infection.MethodsWX-081 in vitro antibacterial activity was assessed based on growth inhibition of M. abscessus standard strain ATCC19977 and 36 clinical isolates. Maximum tolerated concentrations (MTCs) of WX-081, bedaquiline, and azithromycin and inhibition of M. abscessus growth were assessed in vivo after fluorescently labelled bacilli and drugs were injected into zebrafish. Bacterial counts were analysed using one-way ANOVA and fluorescence intensities of zebrafish tissues were analysed and expressed as the mean ± SE. Moreover, Kaplan-Meier survival analysis was conducted to assess intergroup differences in survival of M. abscessus-infected zebrafish treated with different drug concentrations using a log-rank test, with a p value <0.05 indicating a difference was statistically significant.ResultsDrug sensitivity testing of M. abscessus standard strain ATCC19977 and 36 clinical isolates revealed MICs ranging from 0.12-0.96 µg/mL and MIC50 and MIC90 values of 0.48 µg/mL and 0.96 µg/mL, respectively. Fluorescence intensities of M. abscessus-infected zebrafish tissues was lower after treatment with the WX-081 MTC (62.5 µg/mL) than after treatment with the azithromycin MTC (62.5 µg/mL) and the bedaquiline MTC (15.6 µg/mL). When the concentration of WX-081 increased from 1.95µg/mL to 1/8 MTC(7.81µg/mL), the survival rate of zebrafish at 4-9 dpf decreased from 90.00% to 81.67%.ConclusionWX-081 effectively inhibited M. abscessus growth in vitro and in vivo and prolonged survival of M. abscessus-infected zebrafish, thus indicating that WX-081 holds promise as a clinical treatment for M. abscessus infection

High loading-dose of dupilumab resulted in rapid disease control in pediatric patients with atopic dermatitis

BackgroundThe real-world experience of dupilumab in Chinese is limited, and the initial loading dose has not yet been deeply explored in patients aged <6 years.ObjectiveTo explore the efficacy and safety of dupilumab in Chinese patients with moderate-to-severe atopic dermatitis and investigate the effect of higher loading dose for disease control in patients aged <6 years.MethodsA total of 155 patients were divided into three groups according to age: <6 years, 6-11 years, and >11 years. Among patients aged <6 years, 37 patients received a high loading dose of 300 mg for body weight <15kg or 600 mg for body weight ≥15kg, and another 37 patients received a standard loading dose of 200 mg for body weight <15kg or 300 mg for body weight ≥15kg. Multiple physicians and patient-reported outcome measures were evaluated at baseline and 2, 4, 6, 8, 12, and 16 weeks after dupilumab treatment.ResultsThe proportion of patients showing an improvement of ≥75% in the Eczema Area and Severity Index was 68.0% (17/25), 76.9% (10/13), and 62.5% (25/40) in the aged <6, 6-11, and >11 years groups, respectively, at week 16. After increasing the loading dose, 69.6% (16/23) of patients aged <6 years achieved 4-point improvement in Pruritus Numerical Rating Scale at week 2, compared with 23.5% (8/34) of patients receiving standard loading dose (P < 0.001). Obesity (odds ratio=0.12, 95% confidence interval: 0.02-0.70) was predictive of a poor response to dupilumab treatment, while female (odds ratio=3.94, 95% confidence interval: 1.26-12.31) predicted good response at week 16. The change of serum C-C motif ligand 17(CCL17/TARC) could reflect the response to dupilumab (r = 0.53, P = 0.002 in EASI) among patients aged <18 years. No major adverse events were reported during the treatment.ConclusionsDupilumab was effective and well-tolerated in Chinese patients with atopic dermatitis. The increased loading dose helped achieve rapid pruritus control in patients aged <6 years