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The ketone metabolite β-hydroxybutyrate (βOHB), is reported to be neuroprotective after spinal cord injury (SCI) in rats, but the underlying mechanism remains unknown. The present study aims to investigate effects of βOHB on suppression of oxidative stress and inhibition of class I histone deacetylases (HDACs) in in vivo and in vitro models. Rats were fed with ketogenic diet (KD) or standard diet (SD) for 3 weeks. A C5 hemi-contusion injury was applied to these animals on the 14th day of experiment, and spinal cord samples were harvested on the 1st, 3rd and 7th days after SCI, respectively. The blood ketone levels were significantly higher in the KD groups. KD reduced oxidative stress markers and reactive oxygen species (ROS) products, downregulated the expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)2 and NOX4, and upregulated the expression of forkhead box group O (FOXO)3a, mitochondrial superoxide dismutase (MnSOD), and catalase after SCI. The in vitro study, performed on PC12 cells, indicated that βOHB inhibited H

Lipohypertrophy (LH) is a complication of insulin therapy. We assessed LH prevalence, risk factors, insulin usage, and clinical and health economic effects in China.In four cities, 401 adult patients injecting insulin ≥1 year were surveyed for diabetes/insulin injection history and practices, pen needle reimbursement (PNR), and health resource utilization, followed by structured examination and HbA1c testing. Differences between those with and without LH were evaluated by Student's t-test or the Wilcoxon rank sum test. Insulin costs were calculated.Patients were 59.6 ± 11.5 years old; 50% male; 93.5% type 2 diabetes. LH prevalence was 53.1%. Compared to those without LH, patients with LH had higher body mass index (BMI; 26 vs. 24.8 kg/mLH is common in China and associated with worse glycemic control, despite nearly one-third greater insulin consumption, with large cost implications. Proper injection technique education may reduce LH prevalence.

Background: Medulloblastoma (MB) is the most common and deadliest primary brain tumor in children that accounts for 15-20% of all pediatric brain tumors. Despite recent advances in multimodal treatment, the 5-year overall survival of MB patients is approximately 60-70%. Unfortunately, improved outcome have been associated with significant long-term toxicities. Identifying novel targets that drive MB progression is urgently needed. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is a scaffolding protein that functions as a coregulator of several nuclear receptors. Oncogenic PELP1 signaling is implicated in the progression of several cancers including breast, ovarian, prostate, lung, pancreas and colon. However, its role in the progression of medulloblastoma remains unknown. Here, we examined the role of proto-oncogene PELP1 in the progression of MB. Methods: The expression of PELP1 in tumor micro arrays was analyzed using validated PELP1 antibodies for immunohistochemistry. PELP1 expression was determined in vitro by western blotting. PELP1 knockdown cells were generated using PELP1 shRNA lentiviral particles or PELP1 siRNA. The effect of PELP1 knockdown or overexpression was studied using cell proliferation, colony formation and migration using established in vitro assays. Mechanistic studies were conducted using RNA-seq, RT-qPCR, immunohistochemistry, reporter gene assays and signaling analysis. Interaction of PELP1 with NF-κB was examined by immunoprecipitation. Mouse orthotopic xenografts models were used for preclinical evaluation of PELP1 knock down. Results: Immunohistochemical analysis of MB tissue microarrays revealed that PELP1 is overexpressed in MB specimens compared to normal brain specimens. Knockdown of PELP1 using PELP1 specific siRNA or shRNA significantly reduced cell proliferation, cell survival, and cell migration of MB cell lines. RNA-seq analysis revealed that PELP1 knockdown significantly downregulated the pathways related to inflammation, angiogenesis and extracellular matrix. Further, gene set enrichment analysis (GSEA) confirmed that the PELP1-regualted genes were negatively correlated with NF-κB, extracellular matrix and angiogenesis. Mechanistic studies showed that PELP1 knockdown reduced the expression of NF-κB reporter gene activity and its target genes. Additionally, knockdown of PELP1 significantly reduced in vivo MB tumor progression in orthotopic models, and improved overall mice survival. IHC analysis demonstrated that the proliferation marker Ki67 and NF- κB targets were significantly downregulated in PELP1 knockdown tumors compared to controls. Conclusions: Taken together, these results provide the evidence that PELP1 could be a potential therapeutic target for therapeutic intervention in medulloblastoma. Citation Format: Yiliao Luo, Gangadhara Reddy Sareddy, Uday P. Pratap, Mengxing Li, Junhao Liu, Prabhakar Pitta-Venkata, Suryavathi Viswanadhapalli, Xiaonan Li, Manjeet Rao, Rajeshwar Rao Tekmal, Ratna K. Vadlamudi. PELP1 is a novel mediator of medulloblastoma progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3485.

The host immune response can be corrupted by cancer cells during tumor progression. Here we showed that B lymphocytes played an important role in promoting murine breast cancer (BCa) development, as B cell-deficient mMT mice displayed virtually abrogated tumor growth from transplanted syngeneic ERa+ breast adenocarcinoma cells, concomitant with reduced PD-L1 expression and increased BCa cell death. In murine BCa tumors and tumor-associated lymph nodes, B cells were the major source of IL-27, a pleotropic cytokine with both pro- and anti-inflammatory functions. Deficiency in IL-27 expression specifically in B cells abolished the BCa tumor growth, showing that the effect of B cells in BCa development was mainly through IL-27 production, as likely induced by TLR ligands in the tumor microenvironment together with CD154 and IL-21 expressed by tumor-infiltrating CD4+ T cells. IL-27 treatment of BCa cells resulted in STAT1 and STAT3 phosphorylation, upregulated PD-L1 gene expression and enhanced cell growth. In addition, IL-27 induced activated B cells to express PD-L1 in vitro, consistent with high levels of PD-L1 expression by B cells in tumors. In humans, IL-27 receptor genes were highly expressed in the breast tissue, at levels comparable to those in lymphoid organs, and high IL-27 gene expression was associated with reduced survival in BCa patients, who displayed increased circulating IL-27 levels. Finally, IL-27 supported human BCa cell growth in the presence of tamoxifen, suggesting a role of IL-27 in the drug resistance. Thus, TLR-fueled IL-27 induction in B cells reinforces PD-L1 expression in the tumor environment to drive BCa cell growth and to promote generation of PD-L1hi B regulatory cells, leading to BCa tumor progression.

The ternary system of molten calcium chloride, potassium chloride and sodium chloride is an important electrolyte in the study of TiO2 electro-deoxidation methods. Therefore, the physicochemical data of the CaCl2–KCl–NaCl ternary system is very useful for optimizing of the electrochemical process. In this paper, the electrical conductivity, molar volume and density of molten CaCl2–KCl–NaCl system were predicted through a new generation geometric model. In order to evaluate the reliability of this method, the conductance of some composition points in the ternary system were also measured by electrochemical impedance spectroscopy (EIS) technique. The results show that the predictions of the model were agreed well with the experiment results. It is expected that this method can be used to solve the shortage of the physicochemical data for multicomponent molten systems.

This paper considers the design of robust H infin filtering problem for switched stochastic discrete time-delay system with missing measurements via switched Lyapunov function approach. Attention is focused on the design of an exponentially stable filter guaranteeing a prescribed noise attenuation level in the H infin sense and missing measurements probability. By using switched Lyapunov functionals, some sufficient conditions in terms of linear matrix inequalities (LMIs) are obtained. Finally, a numerical example is provided to demonstrate the effectiveness and applicability of the proposed design approach.

In this paper, a novel randomized step frequency radar that combined the adaptive waveform design and the off-grid point effect simultaneously in the scheme of weighted Particle Swarm Optimization(PSO) is proposed, and the range and velocity joint estimating are recovered by exploiting sparseness of the targets and by invoking compressed sensing (CS) theory. In this new mechanism, each of the dictionary matrix element was first extended by adopting Taylor expansion to an arbitrary precise off-grid point, instead of only the points in a discrete form. Then by adding the new generated information into the dictionary matrix adaptively, an updated time-varying new dictionary matrix is yielded. Finally, in order to overcome the local minima in the traditional CS theory, a weighted PSO dynamic optimal method is adopted, where the convergence speed is increased due to the weighted factor introduced in the PSO. It is not necessary to know exactly the target parameters when using our approach, instead, coarse coding bounds of target parameters are enough for the algorithm, which can be done once and for all off-line, and it is only necessary to specify the initial scopes of the velocity and the range of the target. The proposed weighted PSO based waveform design approach has the potential to achieve much higher estimation accuracy, a faster convergence speed and robustness against unpredictable perturbations for range, a high precision in randomized step frequency radar.

In this paper, a novel randomized step frequency radar with weighted PSO is proposed to recover the range and velocity joint estimating by exploiting sparseness of the targets and invoking compressed sensing (CS) theory. In this algorithm, we abandons the exhaustive list method in the Orthogonal Matching Pursuit (OMP) scheme, which is easy to cause performance degradation in the radar system. Instead, a weighted PSO dynamic optimal method is adopted, where the convergence speed is increased due to the weighted factor introduced in the Particle Swarm Optimization (PSO). The primary advantage of this method lies in being less sensitive to the initial value of target parameters in the case of online optimization process. Moreover, this method overcomes the limitation that the initial parameters must be selected close to the true value of the target, which is not constant in many cases. It is not necessary to know exactly the target parameters when using our approach, instead, coarse coding bounds of target parameters are enough for the algorithm, which can be done once and for all off-line, and it is only necessary to specify the initial scopes of the velocity and the range of the target. Simulation results demonstrate that the proposed weighted PSO approach provides a faster convergence speed and robustness against unpredictable perturbations for range and velocity joint estimating in randomized step frequency radar.

A pilot pattern across two OFDM symbols with special structure is devised for channel estimation in OFDM systems with IQ imbalance at receiver. Based on this pilot pattern, a high-efficiency time-domain (TD) least square (LS) channel estimator is proposed to significantly suppress channel noise by a factor N/(L+1) in comparison with the frequency-domain LS one in [1] where N and L+1 are the total number of subcarriers and the length of cyclic prefix, respectively. Following this, a low-complexity frequency-domain (FD) Gaussian elimination (GE) equalizer is proposed to eliminate IQ distortion by using only 2N complex multiplications per OFDM symbol. From simulation, the proposed scheme TD-LS/FD-GE using only two pilot OFDM symbols achieves the same bit error rate (BER) performance under ideal channel knowledge and no IQ imbalances at low and medium signal-to-noise ratio (SNR) regions whereas these compensation schemes including FD-LS/Post-FFT LS, FD-LS/Pre-FFT Corr, and SPP/Pre-FFT Corr in [1] require about twenty OFDM training symbols to reach the same performance where A/B denotes compensation scheme with A being channel estimator and B being equalizer., 17 pages, 6 figures

In this paper, a robust H ∞ filter for networked control system is designed. A continuous model of networked control system is investigated and it is denoted by the one that is similar to time-delay system, through some assumption and transformation. Because only limited information can be transported in the network, time-invariant logarithmic quantization is considered in the output of system. The filtering error system designed in this paper is robustly asymptotically stable and fulfils the given H ∞ performance level. Based on a linear matrix inequality approach, a solving method of the filter is provided. A numerical example is given to show the effectiveness of the method.

In networked systems, observation data transmitted to the estimator through limited bandwidth channels may be lost. In this paper, we study the robust H ∞ filtering problem for stochastic switch system with missing measurement, and give the way to choose switching strategy. The missing measurement is described by a binary switching sequence satisfying a conditional probability distribution. The designed filter make the filtering error system stochastically asymptotically stable and with H ∞ performance.

ADMA (asymmetric ω- N G , N G -dimethylarginine), an endogenous inhibitor of NOS (NO synthase), has been shown to be an independent predictor of cerebrovascular disorders. DDAH2 (dimethylarginine dimethylaminohydrolase 2) promotes the metabolism of ADMA and plays a key role in the regulation of the acute inflammatory response. We hypothesized that genetic variation in DDAH2 might alter the susceptibility to ICH (intracerebral haemorrhage). The hypothesis was tested in two independent case-control studies. We used a haplotype-tagging SNP (single nucleotide polymorphism) approach to identify tag SNPs in DDAH2 . The SNPs were genotyped in 1603 stroke patients and 1525 control subjects. The study was replicated in another independent case-control study including 322 stroke patients and 891 control subjects. A promoter variant −449C/G (rs805305) in DDAH2 was identified and found to be in complete linkage disequilibrium with the only tag SNP (rs707916) in the region containing DDAH2 . Genotype analyses were conducted for both dominant and additive models. The C allele of the −449 locus resulted in a significantly reduced risk of ICH {dominant model: OR (odds ratio), 0.51 [95% CI (confidence interval), 0.38–0.68], P =6.60×10 −6 ; additive model: OR, 0.64 (95% CI, 0.52–0.80), P =5.21×10 −5 } than the wild-type genotype. No association was observed between the DDAH2 variant and atherothrombotic stroke. The findings were replicated in the second independent population. In conclusion, our results suggest that the DDAH2 common variant may play a protective role in the development of ICH, implicating that the DDAH2/ADMA pathway may act as a critical regulator of cerebral small-vessel disorders.

Stroke is a common complex trait and does not follow Mendelian pattern of inheritance. Gene-gene or gene-environment interactions may be responsible for the complex trait. How the interactions contribute to stroke is still under research. This study aimed to explore the association between gene-gene interactions and stroke in Chinese in a large case-control study. Nearly 4,000 participants were recruited from seven clinical centers. Eight variants in five candidate genes were examined for stroke risk. Gene-gene interactions were explored by using Generalized Multifactor Dimensionality Reduction (GMDR). A significant gene-gene interaction was found by GMDR. The best model including MTHFR C677T, ALOX5AP T2354A and NOTCH3 C381T scored 10 for Cross-Validation Consistency and 9 for Sign Test (P = 0.0107). The individuals with combination of MTHFR 677TT, ALOX5AP 2354AA and NOTCH3 381TT/TC had a significantly higher risk of thrombotic stroke (OR 3.165, 95% CI 1.461-6.858, P = 0.003). Our results show that combination of these alleles conferred higher risk for stroke than single risk allele. The gene-gene interaction may serve as a novel area for stroke research. The three-locus combination may change the susceptibility of particular subjects to the disease.

eNOS (endothelial NO synthase) plays a critical role in the development of ventricular remodelling and cardiac hypertrophy. The purpose of the present study was to determine whether three common variants in NOS3 (the eNOS gene) are associated with the risk of LVH [LV (left ventricular) hypertrophy] in patients with essential hypertension. Three NOS3 genetic variants, −T786C (rs2070744), eNOS4a/b and +G894T (rs1799983), were genotyped in two independent case-control studies: the first study consisted of 1061 hypertensive patients with LVH and 1118 hypertensive patients without LVH, and the second sample consisted of 120 patients with LVH and 223 patients without LVH. Echocardiographic measurements were obtained in all of the hypertensive patients. Only the +G894T (E298D) variant of NOS3 was associated with a higher risk of LVH {OR (odds ratio), 1.67 [95% CI (confidence interval), 1.19–2.36]; P

In this paper, the problem of designing a robust L2 - Linfin filter for networked control systems is investigated. A model is considered that take into account the network-induced delay and data dropout. Aim at the systems' uncertainty, the uncertainty correlated with the states of plant is joined. Through the approach of Lyapunov-Krasovskii, the performance of L2 - Linfin is transformed to a set of linear matrix inequalities that will be solved by a series of congruence transform. A numerical example is given to show the effectiveness of the method.

A method was reported to determine the internal rotation of the birefringence axes in polarization-maintaining optical fibers. Four types of fibers from five manufacturers are used to test the applicability of the method, and the results show an approximate uniform unidirectional counterclockwise internal rotation or a right screw with different magnitudes. Our experiment indicated that the repeatability and reproducibility of this method are satisfactory, and the simplicity of measurement and hardware requirements for characterizing the optical fiber for high-precision fiber-optic sensing systems made it easy to realize in ordinary laboratories.

In this paper, a new class of Markovian jump linear system model with polytopic parameter uncertainty, continuous disturbance and discrete disturbance is introduced. The transition rate matrix of the Markov process and the parameters of the system are either exactly known, or unknown but belong to a given polytope. The general criteria for the stochastic stability of this model and the method for designing a robust stable linear time-invariant H ∞ filter under sampled measurements are derived in terms of certain linear matrix inequalities (LMIs). Finally, a numerical example is given to show that the method is effective and feasible.