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Photothermal agents (PTAs) with minimized side effects are critical for transforming cancer photothermal therapy (PTT) into clinical applications. However, most currently available PTAs lack true selective activation to reduce side effects because of heavy spectral overlap between photothermal agents and their corresponding products. This study reports the construction of activatable PTAs with target-initiated large spectral separation for highly effective reduction of side effects. Such designed probes involve two H

Objective Hydroxychloroquine (HCQ) is widely used in patients with systemic lupus erythematosus (SLE) due to its immunomodulatory properties. Antidepressants are commonly used in patients with fibromyalgia syndrome (FMS). Both HCQ and antidepressants are reported to cause QTc prolongation, which potentially increases the risk for a lethal ventricular arrhythmia that can result in sudden death. The objective of the study is to investigate the risk of QTc prolongation associated with HCQ use concomitantly with antidepressants in lupus patients with FMS. Methods Outpatient 12-lead electrocardiograms (ECGs) were extracted from an electronic medical record and QTc intervals were calculated using the Bazett’s formula. QTc intervals in 135 lupus patients treated with HCQ with or without antidepressants were analyzed. Results We found taking HCQ was associated with mild QTc prolongation, and the prolongation was not affected by the length of time of HCQ use or the accumulated dose of HCQ. Concurrent use of HCQ and antidepressants had not further increased QTc intervals in this cohort. However, four patients on HCQ alone and three patients on HCQ and antidepressants were found QTc interval more than 500 milliseconds and most of these patients had underlying cardiological conditions. Conclusions It is important to evaluate lupus patient with ECG before and after starting HCQ, though our study suggests that while HCQ use did prolong the QTc in some, but the overall prolongation was subclinical, with or without antidepressants. ECG monitoring therefore is essential to identify new changes potentially related to drug use.

Objective To assess the role of STAT4 activation in driving pathogenic follicular helper T (Tfh) cell secretion of the cytokines interleukin-21 (IL-21) and interferon-γ (IFNγ) in murine and human lupus. Methods The effect of STAT4-dependent Tfh cell signaling on cytokine production and autoreactive B cell maturation was assessed temporally during the course of lupus in a murine model, with further assessment of Tfh cell gene transcription performed using RNA-Seq technology. STAT4-dependent signaling and cytokine production were also determined in circulating Tfh-like cells in patients with systemic lupus erythematosus (SLE), as compared to cells from healthy control subjects, and correlations with disease activity were assessed in the Tfh-like cells from SLE patients. Results IL-21- and IFNγ-coproducing Tfh cells expanded prior to the detection of potentially pathogenic IgG2c autoantibodies in lupus-prone mice. Tfh cells transcriptionally evolved during the course of disease with acquisition of a STAT4-dependent gene signature. Maintenance of Tfh cell cytokine synthesis was dependent upon STAT4 signaling, driven by type I IFNs. Circulating Tfh-like cells from patients with SLE also secreted IL-21 and IFNγ, with STAT4 phosphorylation enhanced by IFNβ, in association with the extent of clinical disease activity. Conclusion We identified a role for type I IFN signaling in driving STAT4 activation and production of IL-21 and IFNγ by Tfh cells in murine and human lupus. Enhanced STAT4 activation in Tfh cells may underlie pathogenic B cell responses in both murine and human lupus. These data indicate that STAT4 guides pathogenic cytokine and immunoglobulin production in SLE, demonstrating a potential therapeutic target to modulate autoimmunity.

Long non-coding RNA (lncRNA) LINC00899 is one kind cytoplasmic lncRNA, however, there is rarely little information about its function in physiological process. Here, we demonstrated that lncRNA LINC00899 was upregulated in acute myeloid leukaemia (AML) cells and was quite correlated with poor prognosis of AML patients. High expression of LINC00899 in AML cells could promote cell proliferation and inhibit cell apoptosis, and facilitate the progression of AML consequently both in vitro and in vivo. Besides, LINC00899 acted as a molecular sponge of miR-744-3p. Furthermore, we characterized YY1 as the direct target of miR-744-3p, and LINC00899/miR-744-3p interaction modulated YY1 expression in AML cells. Finally, we verified LINC00899 modulated AML cell proliferation and apoptosis via regulating YY1. Our study revealed novel mechanism about how did lncRNA LINC00899 execute function in AML and thus provided potential therapeutic interventions for AML. SIGNIFICANCE OF THE STUDY: LncRNA LINC00899 is upregulated in AML cells and is correlated with poor prognosis of AML patients. LncRNA LINC00899 mediates cell proliferation and apoptosis of acute myeloid leukaemia cells. Knockdown of LINC00899 inhibited the growth of xenograft glioma tumour in vivo. LINC00899 acts as a molecular sponge of miR-744-3p. YY1 is the downstream target of LINC00899/miR-744-3p signalling.

Novel dual-emission fluorescent nitrogen-doped carbon dots (N-CDs) were synthesized by a facile one-pot hydrothermal method using ascorbic acid and rhodamine B as precursors and melamine as nitrogen source. The obtained N-CDs exhibited dual-emitting peaks at 435 nm and 578 nm under the single excitation of 350 nm. The fluorescence at 578 nm was more effectively quenched by indigo carmine (IC) based on the internal filtration effect and aggregation-induced emission quenching. Meanwhile, the apparent color change of N-CDs from pink to blue-purple after adding various concentrations of IC could be clearly observed with the naked eye. Therefore, a ratiometric fluorescent and colorimetric dual-signal probe based on N-CDs was developed for IC detection with high selectivity and sensitivity. The addition of IC caused the ratiometric fluorescent value (F

The power angle of the synchronous generator is a key indicator that reflects the transient stability of the power system. The accurate measurement of the power angle is thus important to ensure the stable operation of the power system. In this paper, a real-time power angle measurement of synchronous generator is proposed, which is based on the second-order generalized integrator with frequency-locked loop (SOGI-FLL). Firstly, the terminal voltage and current of synchronous generator (SG) are collected in real-time. Secondly, the fundamental-frequency positive sequence signal is extracted from the instantaneous sampling data by using the SOGI-FLL. Then the generator vector equation is used to calculate the power angle. Meanwhile, the power angle error existing in the transient process is compensated by using the generator swing equation. The one machine infinite bus (OMIB) system is considered when building the power angle monitoring model of SG. Two scenarios under both steady state and transient state are respectively simulated with the MATLAB/Simulink. The simulation results indicate that the proposed method can enable a better real-time calculation with high accuracy for both scenarios.

Permeability is an important input parameter in evaluating formation validity and predicting deliverability; its value is always estimated from porosity or other formation parameters based on the statistical methods. However, glutenite reservoir permeability prediction faces a great challenge due to the strong heterogeneity. In this study, to establish a reasonable model to predict heterogeneous glutenite reservoir permeability, 483 core samples were recovered from the Permian Jiamuhe Formation, Shawan Depression, northwestern Junggar Basin, China for routine physical property experiments; 21 of them were chosen to apply for laboratory nuclear magnetic resonance (NMR) measurements. After introducing the hydraulic flow unit (HFU) theory, these 483 core samples are classified into eight categories based on the flow zone indicator (FZI) difference, and applicative relationships of core-derived porosity and permeability are respectively established for every type of core sample. Meanwhile, based on the deeply analyzing of the expression of FZI and the classic Timur-Coates permeability-based model, a theoretical model of calculating FZI from NMR data is proposed. The involved input parameters are calibrated by using the experimental data of 21 core samples. After the established models are extended into field applications, the consecutive FZI curve is estimated from NMR logging to classify formations, and the corresponding relationships are used to predict permeability. Comparisons of the predicted FZI and permeability with core-derived results verify the reliability of the proposed models. They can be well used to precisely predict permeability in our target heterogeneous glutenite reservoirs.

Due to the randomness and instability of photovoltaic power generation, accurate power generation forecasting is of great significance to ensure grid stability and economic dispatch. This paper proposes a photovoltaic (PV) power output prediction model based on randomized multi-scale kernels, where the centers of the kernels are extracted by K-means method and the scales are sampled from a pre-defined uniform distribution. Through the experiment analysis, we believe that for generation data, establishing a model according to the season can improve the prediction accuracy. Compared with the existing models, the results show that the proposed method in this paper has a better effect on power generation prediction.

The facile preparation of highly fluorescent polymer dots (PDs) still attracts substantial interest. Here, temperature/Fe

The IL-7 receptor alpha chain (IL-7Rα or CD127) can be differentially expressed in memory CD8(+) T cells. Here we investigated whether IL-7Rα could serve as a key molecule in defining a comprehensive landscape of heterogeneity in human effector memory (EM) CD8(+) T cells using high-dimensional Cytometry by Time-Of-Flight (CyTOF) and single-cell RNA-seq (scRNA-seq). IL-7Rα had diverse, but organized, expressional relationship in EM CD8(+) T cells with molecules related to cell function and gene regulation, which rendered an immune landscape defining heterogeneous cell subsets. The differential expression of these molecules likely has biological implications as we found in vivo signatures of transcription factors and homeostasis cytokine receptors, including T-bet and IL-7Rα. Our findings indicate the existence of heterogeneity in human EM CD8(+) T cells as defined by distinct but organized expression patterns of multiple molecules in relationship to IL-7Rα and its possible biological significance in modulating downstream events.

A simple and green method for the synthesis of fluorescent carbon nanospheres (CNs) was proposed using chrysanthemum as a natural precursor and ethylenediamine as the co-reagent. The prepared CNs show strong blue fluorescence in water with quantum yield of 13.7 %, and distinguished fluorescent stability against photobleaching and ion strength. Meanwhile, the fluorescence signal of CNs is reversible and sensitive to temperature in the range of 20-80 °C, which makes CNs useful as a temperature sensor. More importantly, the CNs can serve as excellent fluorescent sensors for detecting MnO

ZnO as a promising electron transport layer (ETL) to TiO2 for perovskite solar cells (PSCs) has achieved a power conversion efficiency (PCE) of 18.9%; however, this is still lower than that obtained for TiO2-based PSCs (higher than 20%). Herein, we report the fabrication of high-efficiency methylammonium (MA) and Cs co-alloyed formamidinium (FA) triple cation perovskite based ZnO PSCs via delicate control of the cation compositions and annealing temperatures. By virtue of structural, morphological, spectral and electrochemical characterizations and analysis, we found that the incorporation of MA and Cs into FA perovskite enables the formation of a highly crystalline black phase perovskite with reduced surface roughness, which inhibits charge recombination and promotes electron transfer at the ZnO/perovskite/spiro-OMeTAD interfaces and hence improves Jsc and FF values of the cell. As a result, the ZnO PSC based on MA0.1FA0.75Cs0.15PbI3 annealed at 110 °C achieved a PCE as high as 20.09%, exceeding the previous highest efficiency recorded for ZnO ETL based PSCs. The optimized MA0.1FA0.75Cs0.15PbI3 material demonstrated excellent reproducibility and long-term cell durability under ambient conditions within 1000 h. Particularly, the incorporation of a small amount of Br into the triple cation perovskite, i.e., MA0.1FA0.75Cs0.15PbI2.9Br0.1 led to a further enhancement in PCE of up to 20.44%, which is comparable with the best-performing MA and Cs-containing FA-based lead halide TiO2 PSCs.

Pore structure is of great importance in tight reservoirs identification and validation evaluation, especially for formations with developed fractured. However, the conventional pore structure evaluation method based on nuclear magnetic resonance (NMR) logging lost its role. This is because the fractures with width lower than 2mm did not have response in the NMR T2 spectrum. Whereas the porosity spectrum, which extracted from the FMI data, was considered to be effective in fractured reservoir pore structure evaluation. In this study, to quantitatively characterize tight glutenite reservoir pore structure in the Jiamuhe Formation in northwest margin of Junggar Basin, northwest China, 90 core samples were drilled for lab mercury injection capillary pressure (MICP) measurement, and the XRMI data (acquired by the Halliburton and be similar with FMI) was processed to acquire the porosity spectrum. The relationship between the MICP curve and the corresponding inverse cumulative curve of porosity spectra was analyzed, and the model of piecewise power function, which can be used to transform the porosity spectrum as pseudo capillary pressure (Pc) curve, was established. By using this model, consecutive pseudoPc curves can be constructed in the intervals with which XRMI data was acquired, and the corresponding pore structure evaluation parameters, such as the average pore throat radius, the maximum pore throat radius, the threshold pressure, and so on, can also be predicted. Meanwhile, a permeability prediction model based on the Swanson parameter, also established. By combining with the constructed consecutive pseudoPc curves, the pore structure evaluation parameters and permeabilities, several hydrocarbon production potential formations were identified, and this was verified by the drill stem test (DST) data.

The Carboniferous igneous rocks in the western margin of Junggar Basin, western China developed large-scale oil reservoirs. Hongshan-Zhongguai Bulge, the location of Jinlong Oilfield where oil and gas exploration in igneous rocks has achieved efficient breakthroughs in recent years, was studied as an example, because a large number of igneous rocks and crude oil samples are available in this area. The Carboniferous igneous rock reservoirs are typical fault-controlled block reservoirs, and are distributed in a stepped-like manner. Based on analysis of biomarkers, inclusions and reservoir cores under microscope, the oil sources, filling history and major controls for the igneous rock reservoirs that associated with accumulation mechanisms were studied. The biomarker geochemistry reveals that the oil in the igneous rocks was derived from the Permian source rocks including formations of Jiamuhe, Fengcheng and Lower Wuerhe (P2w), and the P2w is the primary source rock. Three important periods of oil charging in the igneous rock reservoirs are suggested: Late Triassic to Early Jurassic, Early Cretaceous, and Late Cretaceous to Early Tertiary. Volcanic breccia of eruptive facies is most favorable for igneous rock reservoir, followed by andesite of effusive facies. Strike-slip faults, overthrust faults and secondary normal faults formed into a fault network, interwoven with the unconformities in the top of the Carboniferous system and within the Permian strata, forming a vertical and horizontal three-dimensional petroleum migration pathway. Hydrocarbons migrated to igneous rock reservoirs from the Permian source rocks along strike-slip faults. The faults communicate the hydrocarbon source rocks with the upper weathering crust reservoirs and control the petroleum distribution. Due to weathering and leaching below the unconformity at the top of the igneous rock reservoirs, oil and gas are most abundant in the upper 150 m. In the fault belt the rocks are cemented by minerals of carbonate, clay, zeolite, quartz, and serpentine, and these types of cementation along faults were recognized as important factors for laterally sealing oil and gas in igneous rock reservoirs.

Fabricating a 1D electron transport layer (ETL) with bifunctionalities capable of effectively extracting electrons from a fully covering perovskite layer and synergistically blocking charge recombination between electrons in the cathode and holes in the perovskite is of great importance for high performance perovskite solar cells (PSCs). Herein, we report a compact and even ZnO:I nanopillar planar ETL that enables the deposition of a fully covering and highly uniform perovskite layer by a facile one-step spin-coating method. We find that the crystal growth of 1D ZnO along the [0001] direction of a hexagonal single crystal is largely suppressed owing to iodine doping, which leads to a low-aspect-ratio and dense 1D nanopillar aligned architecture, and thus promotes one-step deposition of the perovskite layer. As characterized by optical spectroscopy, Kelvin probe force microscopy, and electrochemical assays, the resultant ZnO:I nanopillar ETL film exhibits high optical transparency, a reduced work function and superior electron extraction ability. As a result, the optical–electrical conversion efficiency is promoted to as high as 18.24%, exceeding the previous highest efficiency recorded for 1D ETL based CH3NH3PbI3 PSCs. The enhanced performance is discussed in detail based on a well-matched work function between ZnO:I and the perovskite, fast electron extraction from the perovskite into the ZnO:I ETL, and improved electron transport rate and retarded charge recombination at the 1D ZnO:I ETL/perovskite interface. This work provides a novel and efficient 1D ETL via alien element doping and crystal oriented growth control for maximizing PSC performance.

The IL-7 receptor alpha chain (IL-7Rα or CD127) can be differentially expressed in memory CD8+ T cells. Here we investigated whether IL-7Rα could serve as a key molecule in defining a comprehensive landscape of heterogeneity in human effector memory (EM) CD8+ T cells using high-dimensional Cytometry by Time-Of-Flight (CyTOF) and single-cell RNA-seq (scRNA-seq). IL-7Rα had diverse, but organized, expressional relationship in EM CD8+ T cells with molecules related to cell function and gene regulation, which rendered an immune landscape defining heterogeneous cell subsets. The differential expression of these molecules likely has biological implications as we found in vivo signatures of transcription factors and homeostasis cytokine receptors, including T-bet and IL-7Rα. Our findings indicate the existence of heterogeneity in human EM CD8+ T cells as defined by distinct but organized expression patterns of multiple molecules in relationship to IL-7Rα and its possible biological significance in modulating downstream events.

The key issue in partial least squares (PLS) is the computation of loading weight which describes the relations between the responses and observation variables. In this paper, we propose a simple modified PLS regression method to adaptively compute the loading weight. The weight is solved according to a regularization framework with a similarity constraint to keep the spectra–concentrate relations and meanwhile to penalty the variables with a large distance to the response. The regularized weights can accurately reflect the spectra–concentrate relations, and lead to a good-fitting and parsimonious model which is less sensitive to the latent variables. The proposed method is compared, in terms of root mean square errors of prediction, correlation coefficient and cumulative explained variance, to PLS on simulated and real near-infrared spectra data sets. Experimental results demonstrate the efficacy and effectiveness of the proposed method.

In this study, we investigated the correlation between CYP2C9 gene polymorphism and maintenance dose of Warfarin in 300 patients who were the Han population derived from the Affiliated Yan An Hospital of Kunming Medical University in Yunnan Province of China, subjected to the operation of cardiac valve replacement and Warfarin oral administration post operation from 2008 to 2009 by detecting the genotypes and Allele Frequency at the three candidate loci (CYP2C9*2i¼ŒCYP2C9*3 and CYP2C9*c_65) of CYP2C9 gene from the blood samples. Polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) assay and DNA sequencing were used to ascertain the genotypes and their corresponding distribution rate. The maintenance dose of Warfarin administered in anticoagulant therapy among the CYP2C9*3 genetypes found in our experiment showed: A/A wild type > A/C heterozygote>C/C homozygote, suggesting that patients with C mutation need the lowest maintenance dose of Warfarin among the three genotypes found in this study. Our results will shed a new light on the personalized medicine of Warfarin and provide basic and genetic experimental data and foundation for future studies with regard to multiple genes’ effect on Warfarin dorsage in anticogulantant therapy. Key words: Warfarin, maitenance dosage, CYP2C9, gene polymorphism, single nucleotide polymorphism (SNP), restriction fragment length polymorphism (RFLP), correlation.

Objective: Warfarin is a commonly used anticoagulant with a narrow therapeutic range and large interindividual differences in dosing requirements. Previously, studies have identified that the interindividual variability was influenced by varieties of factors, including age, body size, vitamin K intake, interacting medications, as well as genetic variants. We aimed to investigate the effect of single-nucleotide polymorphisms (SNPs) on the interindividual variability of warfarin dose requirements in Chinese patients. Methods: The study population consisted of 300 patients with a stable maintenance dose of warfarin. We examined SNPs in eight genes involving in the biotransformation and mode of action of warfarin (i.e., CYP4F2, CYP2C19, APOE, CALU, EPHX1, PROC, CYP2C9, and GGCX) using the SNaPshot assay. Results: The mean daily warfarin dose in patients carrying CYP2C19 rs3814637CC, CYP2C9 rs1057910AA, and GGCX rs699664AA genotype was 3.39, 3.34, and 3.51 mg/day, respectively, which was higher than those carrying CYP2C19 rs3814637TT, CYP2C9 rs1057910CC, and rs699664GG genotype (2.00, 0.81, and 3.09 mg/day, respectively). Conclusion: These findings indicate that individuals carrying the CYP2C19 rs3814637CC or CYP2C9 rs1057910AA or GGCX rs699664AA genotype needed higher warfarin doses in the Chinese population.

We propose a stochastic gradient descent algorithm for learning the gradient of a regression function from random samples of function values. This is a learning algorithm involving Mercer kernels. By a detailed analysis in reproducing kernel Hilbert spaces, we provide some error bounds to show that the gradient estimated by the algorithm converges to the true gradient, under some natural conditions on the regression function and suitable choices of the step size and regularization parameters.

Atherosclerosis is an inflammatory disease that is associated with monocyte recruitment and subsequent differentiation into lipid-laden macrophages at sites of arterial lesions, leading to the development of atherosclerotic plaques. PLC is a key member of signaling pathways initiated by G protein-coupled ligands in macrophages. However, the role of this enzyme in the regulation of macrophage function is not known. Here, we studied macrophages from mice lacking PLC beta2, PLC beta3, or both PLC isoforms and found that PLC beta3 is the major functional PLC beta isoform in murine macrophages. Although PLC beta3 deficiency did not affect macrophage migration, adhesion, or phagocytosis, it resulted in macrophage hypersensitivity to multiple inducers of apoptosis. PLC beta3 appeared to regulate this sensitivity via PKC-dependent upregulation of Bcl-XL. The significance of PLC beta signaling in vivo was examined using the apoE-deficient mouse model of atherosclerosis. Mice lacking both PLC beta3 and apoE exhibited fewer total macrophages and increased macrophage apoptosis in atherosclerotic lesions, as well as reduced atherosclerotic lesion size when compared with mice lacking only apoE. These results demonstrate what we believe to be a novel role for PLC activity in promoting macrophage survival in atherosclerotic plaques and identify PLC beta3 as a potential target for treatment of atherosclerosis.

In this article, we characterize the fluorescence of an environmentally sensitive probe for lipid membranes, di-4-ANEPPDHQ. In large unilamellar lipid vesicles (LUVs), its emission spectrum shifts up to 30nm to the blue with increasing cholesterol concentration. Independently, it displays a comparable blue shift in liquid-ordered relative to liquid-disordered phases. The cumulative effect is a 60-nm difference in emission spectra for cholesterol containing LUVs in the liquid-ordered state versus cholesterol-free LUVs in the liquid-disordered phase. Given these optical properties, we use di-4-ANEPPDHQ to image the phase separation in giant unilamellar vesicles with both linear and nonlinear optical microscopy. The dye shows green and red fluorescence in liquid-ordered and -disordered domains, respectively. We propose that this reflects the relative rigidity of the molecular packing around the dye molecules in the two phases. We also observe a sevenfold stronger second harmonic generation signal in the liquid-disordered domains, consistent with a higher concentration of the dye resulting from preferential partitioning into the disordered phase. The efficacy of the dye for reporting lipid domains in cell membranes is demonstrated in polarized migrating neutrophils.

SummaryLeukocyte chemoattractants regulate many leukocyte functions, including leukocyte chemotaxis, via the Rho family of small GTPases that include RhoA, Cdc42, and Rac [1–4]. Previous work has revealed mechanisms by which chemoattractants regulate RhoA and Cdc42 in mouse neutrophils [5–8], but the mechanisms for regulation of Rac remain unclear even though Rac is important for neutrophil functions [9–13]. Here, we characterized P-Rex1, a Gβγ and PIP3-regulated guanine nucleotide exchange factor that was initially identified as a Rac activator in response to chemoattractants [14], for its roles in the regulation of Rac activity and neutrophil functions. We generated a mouse line in which the P-Rex1 gene is disrupted and found that P-Rex1 deficiency did not significantly affect Rac1 activation but diminished Rac2 activation in response to a chemoattractant fMLP in mouse neutrophils. This preference for Rac2 may partially result from the apparent higher affinity of P-Rex1 for Rac2 than for Rac1 because P-Rex1 was more readily immunoprecipitated with Rac2S17N than Rac1S17N. In addition, P-Rex1 deficiency significantly attenuated fMLP-induced F actin formation and superoxide production without affecting LPS- or PMA-induced production. Furthermore, P-Rex1 deficiency caused a chemotactic defect that is primarily attributed to a reduction in the migration rate rather than directionality.

PTEN (phosphatase and tensin homologue) is a phosphatase that dephosphorylates both protein and phosphoinositide substrates. It is mutated in a variety of human tumours and has important roles in a diverse range of biological processes1,2,3,4, including cell migration5,6,7 and chemotaxis8,9. PTEN's intracellular localization and presumably activity are regulated by chemoattractants in Dictyostelium10,11 and mouse neutrophils12. However, the mechanisms for its regulation remain elusive. Here we show that RhoA and Cdc42, members of the Rho family of small GTPases13,14,15,16, regulate the intracellular localization of PTEN in leukocytes and human transfected embryonic kidney cells. In addition, active RhoA is able to stimulate the phospholipid phosphatase activity of PTEN in human embryonic kidney cells and leukocytes, and this regulation seems to require RhoA's downstream effector, RhoA-associated kinase (Rock). Furthermore, we have identified key residues on PTEN that are required for its regulation by the small GTPase, and show that small GTPase-mediated regulation of PTEN has a significant role in the regulation of chemotaxis.

This paper presents a new robust adaptive sliding-mode control scheme for a class of nonlinear uncertain time-delay systems. By using a synthetic performance index, stable sliding manifold and memoryless robust adaptive sliding mode controller are designed to stabilize the closed-loop systems. Compared with the traditional sliding control approaches, the proposed scheme considers the reaching phase and sliding motion phase as a whole, which can simplify the design of controller and reduce the chattering. Furthermore, the feasibility for the proposed controller is studied and some intuitionistic feasibility criterions are given. Simulation results illustrate the obtained results.

This paper proposes an adaptive elastic net for sparse high-dimension regression by incorporating the adaptive penalty mechanism into the elastic net. Under a partial orthogonality condition, the initial univariate regression estimator is shown to be zero-consistent, based on which the consistent variable selection and the asymptotic estimation normality is obtained. In addition, the controllable group selection capability is also achieved by properly selecting a special rescaling factor.

Follicular helper T (TFH) cells, defined by expression of the surface markers CXCR5 and programmed death receptor-1 (PD-1) and synthesis of IL-21, require upregulation of the transcriptional repressor Bcl6 for their development and function in B cell maturation in germinal centers. We have explored the role of B cells and the cytokines IL-6 and IL-21 in the in vivo regulation of Bcl6 expression and TFH cell development. We found that TFH cells are characterized by a Bcl6-dependent downregulation of P-selectin glycoprotein ligand 1 (PSGL1, a CCL19- and CCL21-binding protein), indicating that, like CXCR5 and PD-1 upregulation, modulation of PSGL1 expression is part of the TFH cell program of differentiation. B cells were neither required for initial upregulation of Bcl6 nor PSGL1 downregulation, suggesting these events preceded T–B cell interactions, although they were required for full development of the TFH cell phenotype, including CXCR5 and PD-1 upregulation, and IL-21 synthesis. Bcl6 upregulation and TFH cell differentiation were independent of IL-6 and IL-21, revealing that either cytokine is not absolutely required for development of Bcl6+ TFH cells in vivo. These data increase our understanding of Bcl6 regulation in TFH cells and their differentiation in vivo and identifies a new surface marker that may be functionally relevant in this subset.

Background Rho GTPases are known to play important roles in regulating multiple cellular processes that include cell polarization and migration. Among these Rho GTPases, Rac has been shown to be essential for F actin formation and cell migration. P-Rex1 is a guanine nucleotide exchange factor (GEF) that was previously found to mediate the activation of Rac2, but not Rac1, in mouse neutrophils. Objectives Here we examined the role of P-Rex1 in mouse macrophages and atherogenesis. Methods and results PBD (p21 binding domain) pull down assay was performed to compare the Rac1 activation in WT and P-Rex1-deficient macrophage. In addition, transwell assay was conducted to compare chemotaxis of WT and P-Rex1-deficient macrophage. We found that P-Rex1 is a major Rac1 regulator in mouse macrophages as its deficiency significantly compromises macrophage chemotaxis, superoxide production (SOD), and Rac1 activation in response to chemoattractants. The potential role of P-Rex1 in atherogenesis is also investigated by transferring P-Rex1-deficient bone marrow cells to LDLR deficient mice. Contrary to our prediction, P-Rex1 deficiency did not alter atherogenesis, suggesting chemoattractant-induced macrophage migration may not have a significant role in atherogenesis. Conclusions P-Rex1 is one of the major GEFs in macrophage regulating Rac1 activation and chemotaxis.