Increased levels of soluble CD226 in sera accompanied by decreased membrane CD226 expression on peripheral blood mononuclear cells from cancer patients

<p>Abstract</p> <p>Background</p> <p>As a cellular membrane triggering receptor, CD226 is involved in the NK cell- or CTL-mediated lysis of tumor cells of different origin, including freshly isolated tumor cells and tumor cell lines. Here, we evaluated soluble CD226 (sCD226) levels in sera, and membrane CD226 (mCD226) expression on peripheral blood mononuclear cells (PBMC) from cancer patients as well as normal subjects, and demonstrated the possible function and origin of the altered sCD226, which may provide useful information for understanding the mechanisms of tumor escape and for immunodiagnosis and immunotherapy.</p> <p>Results</p> <p>Soluble CD226 levels in serum samples from cancer patients were significantly higher than those in healthy individuals (<it>P </it>< 0.001), while cancer patients exhibited lower PBMC mCD226 expression than healthy individuals (<it>P </it>< 0.001). CD226-Fc fusion protein could significantly inhibit the cytotoxicity of NK cells against K562 cells in a dose-dependent manner. Furthermore, three kinds of protease inhibitors could notably increase mCD226 expression on PMA-stimulated PBMCs and Jurkat cells with a decrease in the sCD226 level in the cell culture supernatant.</p> <p>Conclusion</p> <p>These findings suggest that sCD226 might be shed from cell membranes by certain proteases, and, further, sCD226 may be used as a predictor for monitoring cancer, and more important, a possible immunotherapy target, which may be useful in clinical application.</p

Utilizing Patient-Derived Epithelial Ovarian Cancer Tumor Organoids to Predict Carboplatin Resistance

The development of patient-derived tumor organoids (TOs) from an epithelial ovarian cancer tumor obtained at the time of primary or interval debulking surgery has the potential to play an important role in precision medicine. Here, we utilized TOs to test front-line chemotherapy sensitivity and to investigate genomic drivers of carboplatin resistance. We developed six high-grade, serous epithelial ovarian cancer tumor organoid lines from tissue obtained during debulking surgery (two neoadjuvant-carboplatin-exposed and four chemo-naïve). Each organoid line was screened for sensitivity to carboplatin at four different doses (100, 10, 1, and 0.1 µM). Cell viability curves and resultant EC50 values were determined. One organoid line, UK1254, was predicted to be resistant to carboplatin based on its EC50 value (50.2 µM) being above clinically achievable Cmax. UK1254 had a significantly shorter PFS than the rest of the subjects (p = 0.0253) and was treated as a platinum-resistant recurrence. Subsequent gene expression analysis revealed extensively interconnected, differentially expressed pathways related to NF-kB, cellular differentiation (PRDM6 activation), and the linkage of B-cell receptor signaling to the PI3K–Akt signaling pathway (PI3KAP1 activation). This study demonstrates that patient-derived tumor organoids can be developed from patients at the time of primary or interval debulking surgery and may be used to predict clinical platinum sensitivity status or to investigate drivers of carboplatin resistance

The Genetic Polymorphisms of HLA Are Strongly Correlated with the Disease Severity after Hantaan Virus Infection in the Chinese Han Population

The polymorphism of human leukocyte antigen (HLA), which is a genetic factor that influences the progression of hemorrhagic fever with renal syndrome (HFRS) after Hantaan virus (HTNV) infection, was incompletely understood. In this case-control study, 76 HFRS patients and 370 healthy controls of the Chinese Han population were typed for the HLA-A, -B, and -DRB1 loci. The general variation at the HLA-DRB1 locus was associated with the onset of HFRS (P<0.05). The increasing frequencies of HLA-DRB1*09 and HLA-B*46-DRB1*09 in HFRS patients were observed as reproducing a previous study. Moreover, the HLA-B*51-DRB1*09 was susceptible to HFRS (P=0.037; OR =3.62; 95% CI: 1.00–13.18). The increasing frequencies of HLA-B*46, HLA-B*46-DRB1*09, and HLA-B*51-DRB1*09 were observed almost in severe/critical HFRS patients. The mean level of maximum serum creatinine was higher in HLA-B*46-DRB1*09 (P=0.011), HLA-B*51-DRB1*09 (P=0.041), or HLA-B*46 (P=0.011) positive patients than that in the negative patients. These findings suggest that the allele HLA-B*46 and haplotypes HLA-B*46-DRB1*09 and HLA-B*51-DRB1*09 in patients could contribute to a more severe degree of HFRS and more serious kidney injury, which improve our understanding of the HLA polymorphism for a different outcome of HTNV infection

Manipulating the 3D organization of the largest synthetic yeast chromosome

Whether synthetic genomes can power life has attracted broad interest in the synthetic biology field. Here, we report de novo synthesis of the largest eukaryotic chromosome thus far, synIV, a 1,454,621-bp yeast chromosome resulting from extensive genome streamlining and modification. We developed megachunk assembly combined with a hierarchical integration strategy, which significantly increased the accuracy and flexibility of synthetic chromosome construction. Besides the drastic sequence changes, we further manipulated the 3D structure of synIV to explore spatial gene regulation. Surprisingly, we found few gene expression changes, suggesting that positioning inside the yeast nucleoplasm plays a minor role in gene regulation. Lastly, we tethered synIV to the inner nuclear membrane via its hundreds of loxPsym sites and observed transcriptional repression of the entire chromosome, demonstrating chromosome-wide transcription manipulation without changing the DNA sequences. Our manipulation of the spatial structure of synIV sheds light on higher-order architectural design of the synthetic genomes. </p

Resource Allocation in OFDMA Networks With Imperfect Channel State Information

This letter investigates the effect of imperfect channel state information (CSI) on the performance of radio resource management for a downlink multi-user OFDMA system. It is shown that the imperfect CSI introduces a signal-and-power dependent noise term, which makes the symbol error rate (SER) constellation-point dependent, and yields an error floor on the SER. In addition, a two-step multi-user channel, power and constellation allocation algorithm is proposed to maximize the total network throughput

Prog. Chem.

Microbial electrolysis cells (MEC) invented on the basis of microbial fuel cells (MFC) provide a novel method for biohydrogen production. This paper reviews the research progress of MEC ever since its invention in 2005. The principle of MEC and the evaluating parameters of the system are briefly introduced. Hydrogen production performance of MEC in different system architectures and electrode materials are compared. The existing problems and limiting factors of MEC for its practical utilization are discussed and the future research trends, as well as research approaches of MEC are proposed. Finally, the prospective applications of MEC in hydrogen production from biomass and energy recovery from organic wastewater are also stated.Microbial electrolysis cells (MEC) invented on the basis of microbial fuel cells (MFC) provide a novel method for biohydrogen production. This paper reviews the research progress of MEC ever since its invention in 2005. The principle of MEC and the evaluating parameters of the system are briefly introduced. Hydrogen production performance of MEC in different system architectures and electrode materials are compared. The existing problems and limiting factors of MEC for its practical utilization are discussed and the future research trends, as well as research approaches of MEC are proposed. Finally, the prospective applications of MEC in hydrogen production from biomass and energy recovery from organic wastewater are also stated

Dynamic Time-Of-Use Pricing Strategy for Electric Vehicle Charging Considering User Satisfaction Degree

In order to solve the problem that the static peak-valley price for electric vehicles cannot truly reflect the relationship between electricity supply and demand, as well as the fact that the low utilization rate of renewable energy in the micro-grid, a dynamic time-of-use pricing strategy for electric vehicle charging considering user satisfaction degree is proposed, to achieve the goal of friendly charging for the micro-grid. Firstly, this paper researches the travel patterns of electric vehicles to establish the grid connection scenes and predict the controllable capacity of electric vehicles. Secondly, the charging preferences of different types of users are studied, and a comprehensive satisfaction degree model is set up to obtain different users&rsquo; charging strategies. Furthermore, the paper raises a pricing strategy on account of the dispatching requirements of the micro-grid, and realizes the effective dispatch of electric vehicle charging load based on price signals. Finally, we gain the dynamic time-of-use charging price, using the strategy proposed above, and the economic benefits brought to the micro-grid and electric vehicle users are analyzed, which validates the rationality and effectiveness of the pricing strategy

Coordinated Secondary Frequency Regulation Strategy of Doubly-Fed Induction Generator and Electric Vehicle

Wind turbines can participate in frequency regulation by controlling active power output, but the indeterminacy and volatility of wind power result in low reliability of frequency support. Therefore, as a kind of energy storage system, an electric vehicle is adopted to coordinate with wind turbines to regulate system frequency considering its large-scale development. First, based on the reasonable division of wind speed regions and operation point selection of pitch angle, the de-loading strategy of doubly-fed induction generator for reserve capacity under continuously varying wind speed is proposed. Then, through the combination of rotor speed and pitch angle control, frequency regulation model of a doubly-fed induction generator in whole wind speed range is established. Finally, taking into account the driving demand of electric vehicle owners, through the real-time allocation of system frequency regulation task based on frequency regulation capacity, the coordinated control strategy of doubly-fed induction generator and electric vehicle cluster for secondary frequency regulation is put forward. The simulation results show that the coordinated frequency regulation strategy based on real-time allocation can suppress frequency deviation effectively, and the regulation effect is better than the situations of wind turbine coordinating with the conventional unit or coordinating with electric vehicle cluster based on fixed allocation ratio

Power production enhancement with a polyaniline modified anode in microbial fuel cells

In this paper, an approach of improving power generation of microbial fuel cells (MFCs) by using a HSO(4)(-) doped polyaniline modified carbon cloth anode was reported. The modification of carbon cloth anode was accomplished by electrochemical polymerization of aniline in 5% H(2)SO(4) solution. A dual-chamber MFC reactor with the modified anode achieved a maximum power density of 5.16 W m(-3), an internal resistance of 90 Omega, and a start-up time of 4 days, which was respectively 2.66 times higher, 65.5% lower, and 33.3% shorter than the corresponding values of the MFC with unmodified anode. Evidence from X-ray photoelectron spectroscopy and scanning electron microscopy results proved that the formation of biofilm on the anode surface could prevent the HSO(4)(-) doped polyaniline to be de-doped, and the results from electrochemical tests confirmed that the electrochemical activity of the modified anode was enhanced significantly after inoculation. Charge transfer was facilitated by polyaniline modification. All the results indicated that the polyaniline modification on the anode was an efficient approach of improving the performance of MFCs. (C) 2011 Elsevier B.V. All rights reserved