Lymphoid cells that produce interleukin (IL)-17 cytokines protect barrier tissues from pathogenic microbes but are also prominent effectors of inflammation and autoimmune disease. T helper 17 (Th17) ...cells, defined by RORγt-dependent production of IL-17A and IL-17F, exert homeostatic functions in the gut upon microbiota-directed differentiation from naive CD4+ T cells. In the non-pathogenic setting, their cytokine production is regulated by serum amyloid A proteins (SAA1 and SAA2) secreted by adjacent intestinal epithelial cells. However, Th17 cell behaviors vary markedly according to their environment. Here, we show that SAAs additionally direct a pathogenic pro-inflammatory Th17 cell differentiation program, acting directly on T cells in collaboration with STAT3-activating cytokines. Using loss- and gain-of-function mouse models, we show that SAA1, SAA2, and SAA3 have distinct systemic and local functions in promoting Th17-mediated inflammatory diseases. These studies suggest that T cell signaling pathways modulated by the SAAs may be attractive targets for anti-inflammatory therapies.
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•SAAs direct a distinct Th17 cell differentiation program independently of TGF-β•Expression of SAAs is associated with inflamed colon of IBD patients•Systemic SAAs in serum promote differentiation of pathogenic Th17 cells•Local SAA expression fuels pathogenicity of activated Th17 cells
Serum amyloid A proteins dictate the balance between homeostatic and inflammatory Th17 cells.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
A novel variable reactor based on magnetic flux control is proposed in this paper. The system configuration of the novel variable reactor is presented, while its operational principle and dynamic ...performance are analyzed. Based on the developed variable reactor, a novel integrated power quality controller (IPQC) suitable for microgrid is proposed, which can cater for the peculiar requirements of microgrid power quality, such as the harmonic high penetration, frequent voltage fluctuation and overcurrent phenomenon, and bidirectional power flow and small capacity. For the fundamental, the equivalent impedance of the primary winding is a variable reactor or capacitor. For the nth-order harmonic, the equivalent impedance is very high impedance and acts as a "harmonic isolator." The system control strategy is also analyzed in detail. A set of three-phase IPQC has been constructed. The experimental test results verify the validity of the novel variable reactor and the IPQC.
A novel variable reactor is presented in this paper. The principle of the novel variable reactor is simply addressed. The equivalent impedance of primary winding of the transformer will vary with the ...ratio between the primary and the secondary voltages. For the proposed variable reactor, a novel series power quality controller (SPQC) is developed and its principle is analyzed in detail. The SPQC greatly improves the power utility impedance to harmonics instead of the fundamental and plays the role of isolating the harmonics. Because the novel SPQC is with very high impedance to harmonics, the passive power filter can be reduced. Accordingly, three kinds of reduced single-phase passive power filters are presented. The comparison criterion of reducing passive power filter is described. The SPQC is characterized by perfectly isolating the harmonics, simplified passive power filter design, small rating, and being suitable for two kinds of harmonic sources. The validity of the novel SPQC and excellent filtering characteristic are verified by the experimental results.
Targeting glycolysis has been considered therapeutically intractable owing to its essential housekeeping role. However, the context-dependent requirement for individual glycolytic steps has not been ...fully explored. We show that CRISPR-mediated targeting of glycolysis in T cells in mice results in global loss of Th17 cells, whereas deficiency of the glycolytic enzyme glucose phosphate isomerase (Gpi1) selectively eliminates inflammatory encephalitogenic and colitogenic Th17 cells, without substantially affecting homeostatic microbiota-specific Th17 cells. In homeostatic Th17 cells, partial blockade of glycolysis upon Gpi1 inactivation was compensated by pentose phosphate pathway flux and increased mitochondrial respiration. In contrast, inflammatory Th17 cells experience a hypoxic microenvironment known to limit mitochondrial respiration, which is incompatible with loss of Gpi1. Our study suggests that inhibiting glycolysis by targeting Gpi1 could be an effective therapeutic strategy with minimum toxicity for Th17-mediated autoimmune diseases, and, more generally, that metabolic redundancies can be exploited for selective targeting of disease processes.
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•PPP and OXPHOS compensate for Gpi1 loss in Th17 cells in normoxic environment•Gpi1 is essential in hypoxic inflamed tissue due to reduced OXPHOS compensation•Metabolic redundancy can vary according to the microenvironment•Targeting Gpi1 could be a tolerable approach for therapeutic glycolysis inhibition
Metabolic redundancy differs according to microenvironments, making the glycolysis gene Gpi1 dispensable for homeostatic Th17 cells in normal tissue but essential for pathogenic Th17 cells in hypoxic inflamed tissue.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
We introduce a new method for detecting ultra-diffuse galaxies by searching for over-densities in intergalactic globular cluster populations. Our approach is based on an application of the ...log-Gaussian Cox process, which is a commonly used model in the spatial statistics literature but rarely used in astronomy. This method is applied to the globular cluster data obtained from the PIPER survey, a Hubble Space Telescope imaging program targeting the Perseus cluster. We successfully detect all confirmed ultra-diffuse galaxies with known globular cluster populations in the survey. We also identify a potential galaxy that has no detected diffuse stellar content. Preliminary analysis shows that it is unlikely to be merely an accidental clump of globular clusters or other objects. If confirmed, this system would be the first of its kind. Simulations are used to assess how the physical parameters of the globular cluster systems within ultra-diffuse galaxies affect their detectability using our method. We quantify the correlation of the detection probability with the total number of globular clusters in the galaxy and the anticorrelation with increasing half-number radius of the globular cluster system. The Sérsic index of the globular cluster distribution has little impact on detectability.
With the continuous expansion of the scale of power generated by grid-connected renewable energy, the form and operation characteristics of power grids have undergone significant changes, and the ...power electronic characteristics of power systems are prominent, resulting in the frequent occurrence of wide-band oscillation problems when renewable energy power generation equipment is connected to a power grid. Oscillation has the characteristics of nonlinearity and has an oscillation frequency ranging from a few hertz to several thousand hertz or more, which seriously threatens the stable operation of power grids. This paper summarizes the wide-band oscillation events that occur worldwide under the background of renewable energy access to power grids, classifies the wide-band oscillation events according to the distribution of oscillation frequency bands, and sorts out the characteristics of various oscillations. From the perspectives of the source side and network side, the existing oscillation suppression measures are classified and prospected.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
With the increase in capacitor voltage transformer (CVT) operation life, CVT impedance changes, and the short-time switching of overhead lines, it is very easy to cause a transient oscillation ...accident in which a CVT participates, reduce the insulation level of a CVT, and even induce regional power grid oscillation and easily cause capacitor breakdown, after long-term operation with defects. In this paper, the whole power network, including the generator, power grid, and consumer, is modeled, and the theoretical model of the CVT ferro-resonance connected grid is built. The frequency spectrum analysis, and the measurements of resonance bus voltage and line voltage, were carried out to find the design method of a fast saturation damper (FSD) and its voltage–current characteristics that affect the vibration, based on theory and practice; this paper puts forward effective measures to reduce the resonance effect of a CVT in operation, and avoid the oscillation of the line and even the regional power grid system.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
A novel variable reactor based on transformer is proposed in the paper. In the variable reactor, a transformer with air gap is chosen, and the primary voltage is detected and used as the reference ...signal. A voltage-sourced inverter is applied to track the reference signal in order to yield a controllable voltage, which is applied across the secondary winding of the transformer. When the secondary-controlled voltage and the primary voltage satisfy a proportional condition, the equivalent impedance of primary winding of the transformer will vary continuously. According to the novel variable reactor, a novel shunt power quality controller is proposed and its principle is analyzed in detail. The shunt power quality controller is characterized by parallel topology and single frequency control. The approaches of decreasing the transformer leakage inductance are addressed. The experimental results verify the validity of the shunt power quality controller.
ABSTRACT
We demonstrate the power of Gibbs point process models from the spatial statistics literature when applied to studies of resolved galaxies. We conduct a rigorous analysis of the spatial ...distributions of objects in the star formation complexes of M33, including giant molecular clouds (GMCs) and young stellar cluster candidates (YSCCs). We choose a hierarchical model structure from GMCs to YSCCs based on the natural formation hierarchy between them. This approach circumvents the limitations of the empirical two-point correlation function analysis by naturally accounting for the inhomogeneity present in the distribution of YSCCs. We also investigate the effects of GMCs’ properties on their spatial distributions. We confirm that the distribution of GMCs and YSCCs are highly correlated. We found that the spatial distributions of YSCCs reaches a peak of clustering pattern at ∼250 pc scale compared to a Poisson process. This clustering mainly occurs in regions where the galactocentric distance ≳4.5 kpc. Furthermore, the galactocentric distance of GMCs and their mass have strong positive effects on the correlation strength between GMCs and YSCCs. We outline some possible implications of these findings for our understanding of the cluster formation process.
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