117 research outputs found
On the non-equivalence of Lorenz System and Chen System
In this paper, we prove that the Chen system with a set of chaotic parameters
is not smoothly equivalent to the Lorenz system with any parameters
Plant Expression of Cocaine Hydrolase-Fc Fusion Protein for Treatment of Cocaine Abuse
BACKGROUND: A recently reported cocaine hydrolase (CocH3) fused with fragment crystallizable (Fc) region of human immunoglobulin G1, denoted as CocH3-Fc, is known as a promising therapeutic candidate for the treatment of cocaine overdose and addiction. A challenge for practical therapeutic use of this enzyme exists in the large-scale protein production and, therefore, it is interesting to identify a low-cost and feasible, sustainable source of CocH3-Fc production.
RESULTS: CocH3-Fc was transiently expressed in plant Nicotiana benthamiana leaves. The plant-expressed protein, denoted as pCocH3-Fc, was as active as that expressed in mammalian cells both in vitro and in vivo. However, compared to the mammalian-cell expressed CocH3-Fc protein, pCocH3-Fc had a shorter biological half-life, probably due to the lack of protein sialylation in plant. Nevertheless, the in vivo half-life was significantly extended upon the PEGylation of pCocH3-Fc. The Fc fusion did not prolong the biological half-life of the plant-expressed enzyme pCocH3-Fc, but increased the yield of the enzyme expression in the plant under the same experimental conditions.
CONCLUSIONS: It is feasible to express pCocH3-Fc in plants. Further studies on the pCocH3-Fc production in plants should focus on the development of vectors with additional genes/promoters for the complete protein sialylation and for a better yield
Dietary Modulation of Gut Microbiota Contributes to Alleviation of Both Genetic and Simple Obesity in Children
Gut microbiota has been implicated as a pivotal contributing factor in diet-related obesity; however, its role in development of disease phenotypes in human genetic obesity such as Prader–Willi syndrome (PWS) remains elusive. In this hospitalized intervention trial with PWS (n = 17) and simple obesity (n = 21) children, a diet rich in non-digestible carbohydrates induced significant weight loss and concomitant structural changes of the gut microbiota together with reduction of serum antigen load and alleviation of inflammation. Co-abundance network analysis of 161 prevalent bacterial draft genomes assembled directly from metagenomic datasets showed relative increase of functional genome groups for acetate production from carbohydrates fermentation. NMR-based metabolomic profiling of urine showed diet-induced overall changes of host metabotypes and identified significantly reduced trimethylamine N-oxide and indoxyl sulfate, host-bacteria co-metabolites known to induce metabolic deteriorations. Specific bacterial genomes that were correlated with urine levels of these detrimental co-metabolites were found to encode enzyme genes for production of their precursors by fermentation of choline or tryptophan in the gut. When transplanted into germ-free mice, the pre-intervention gut microbiota induced higher inflammation and larger adipocytes compared with the post-intervention microbiota from the same volunteer. Our multi-omics-based systems analysis indicates a significant etiological contribution of dysbiotic gut microbiota to both genetic and simple obesity in children, implicating a potentially effective target for alleviation
Targeting RNA Polymerase Primary σ70 as a Therapeutic Strategy against Methicillin-Resistant Staphylococcus aureus by Antisense Peptide Nucleic Acid
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) causes threatening infection-related mortality worldwide. Currently, spread of multi-drug resistance (MDR) MRSA limits therapeutic options and requires new approaches to "druggable" target discovery, as well as development of novel MRSA-active antibiotics. RNA polymerase primary σ⁷⁰ (encoded by gene rpoD) is a highly conserved prokaryotic factor essential for transcription initiation in exponentially growing cells of diverse S. aureus, implying potential for antisense inhibition. METHODOLOGY/PRINCIPAL FINDINGS: By synthesizing a serial of cell penetrating peptide conjugated peptide nucleic acids (PPNAs) based on software predicted parameters and further design optimization, we identified a target sequence (234 to 243 nt) within rpoD mRNA conserved region 3.0 being more sensitive to antisense inhibition. A (KFF)₃K peptide conjugated 10-mer complementary PNA (PPNA2332) was developed for potent micromolar-range growth inhibitory effects against four pathogenic S. aureus strains with different resistance phenotypes, including clinical vancomycin-intermediate resistance S. aureus and MDR-MRSA isolates. PPNA2332 showed bacteriocidal antisense effect at 3.2 fold of MIC value against MRSA/VISA Mu50, and its sequence specificity was demonstrated in that PPNA with scrambled PNA sequence (Scr PPNA2332) exhibited no growth inhibitory effect at higher concentrations. Also, PPNA2332 specifically interferes with rpoD mRNA, inhibiting translation of its protein product σ⁷⁰ in a concentration-dependent manner. Full decay of mRNA and suppressed expression of σ⁷⁰ were observed for 40 µM or 12.5 µM PPNA2332 treatment, respectively, but not for 40 µM Scr PPNA2332 treatment in pure culture of MRSA/VISA Mu50 strain. PPNA2332 (≥1 µM) essentially cleared lethal MRSA/VISA Mu50 infection in epithelial cell cultures, and eliminated viable bacterial cells in a time- and concentration- dependent manner, without showing any apparent toxicity at 10 µM. CONCLUSIONS: The present result suggested that RNAP primary σ⁷⁰ is a very promising candidate target for developing novel antisense antibiotic to treat severe MRSA infections
Identification of Renal Long Non-coding RNA RP11-2B6.2 as a Positive Regulator of Type I Interferon Signaling Pathway in Lupus Nephritis
Objective: Lupus nephritis (LN) is one of the most serious complications of systemic lupus erythematosus (SLE). Type I interferon (IFN-I) is associated with the pathogenesis of LN. Long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of SLE, however, the roles of lncRNAs in LN are still poorly understood. Here, we identified and investigated the function of LN-associated lncRNA RP11-2B6.2 in regulating IFN-I signaling pathway.Methods: RNA sequencing was used to analyze the expression of lncRNAs in kidney biopsies from LN patients and controls. Antisense oligonucleotides and CRISPRi system or overexpression plasmids and CRISPRa system were used to perform loss or gain of function experiments. In situ hybridization, imaging flow cytometry, dual-luciferase reporter assay, and ATAC sequencing were used to study the functions of lncRNA RP11-2B6.2. RT-qPCR, ELISA, and western blotting were done to detect RNA and protein levels of specific genes.Results: Elevated lncRNA RP11-2B6.2 was observed in kidney biopsies from LN patients and positively correlated with disease activity and IFN scores. Knockdown of lncRNA RP11-2B6.2 in renal cells inhibited the expression of IFN stimulated genes (ISGs), while overexpression of lncRNA RP11-2B6.2 enhanced ISG expression. Knockdown of LncRNA RP11-2B6.2 inhibited the phosphorylation of JAK1, TYK2, and STAT1 in IFN-I pathway, while promoted the chromatin accessibility and the transcription of SOCS1.Conclusion: The expression of lncRNAs is abnormal in the kidney of LN. LncRNA RP11-2B6.2 is a novel positive regulator of IFN-I pathway through epigenetic inhibition of SOCS1, which provides a new therapeutic target to alleviate over-activated IFN-I signaling in LN
Real-time Monitoring for the Next Core-Collapse Supernova in JUNO
Core-collapse supernova (CCSN) is one of the most energetic astrophysical
events in the Universe. The early and prompt detection of neutrinos before
(pre-SN) and during the SN burst is a unique opportunity to realize the
multi-messenger observation of the CCSN events. In this work, we describe the
monitoring concept and present the sensitivity of the system to the pre-SN and
SN neutrinos at the Jiangmen Underground Neutrino Observatory (JUNO), which is
a 20 kton liquid scintillator detector under construction in South China. The
real-time monitoring system is designed with both the prompt monitors on the
electronic board and online monitors at the data acquisition stage, in order to
ensure both the alert speed and alert coverage of progenitor stars. By assuming
a false alert rate of 1 per year, this monitoring system can be sensitive to
the pre-SN neutrinos up to the distance of about 1.6 (0.9) kpc and SN neutrinos
up to about 370 (360) kpc for a progenitor mass of 30 for the case
of normal (inverted) mass ordering. The pointing ability of the CCSN is
evaluated by using the accumulated event anisotropy of the inverse beta decay
interactions from pre-SN or SN neutrinos, which, along with the early alert,
can play important roles for the followup multi-messenger observations of the
next Galactic or nearby extragalactic CCSN.Comment: 24 pages, 9 figure
Building a learning organization : a study on Xinjiang Tianye Group Co.
56 p.Executive Master of Business Administratio
Remote System for Oil Spill Detection Based on ZigBee and GIS
In order to solve the problem of long delay time and low data precision, a remote system for oil spill detection based on ZigBee and GIS is designed in this paper. This paper analytically summarizes the results obtained from surveying spectral characteristics of spill oil film at sea. M along use of AVHRR and TM data, the image of oil spill in several marine accidents has been processed and identified, and the place and area of oil spill in obtaining images are the same as investigation in the scene of accidents. Simulation results show that the proposed system which bases on the ZigBee and GIS can thus improve overall system performance substantially
An Improved MPC-Based SVPWM Mechanism for NPC Three-Level Z-Source Converters
Model predictive control (MPC) method has been widely used to reduce the computational complexity of the traditional space vector pulse width modulation (SVPWM). However, for a neutral-point clamped three-level Z-source converter, the performance of the normal MPC strategy would highly depend on the computation processing rate because of the multiple times optimization calculation. In this paper, an improved MPC strategy has been developed, with a voltage prediction being designed to replace the current prediction, the calculation of the roll optimization could be effectively simplified significantly, and then the digital execution efficiency would be improved. Besides, in order to obtain a fixed output harmonic frequency, a combination of this improved MPC and SVPWM has been studied and the shoot-through state insertion for the Z-source also has been analyzed in detail. Lastly, comparison experiments have been carried out to make verification of this improved modulation mechanism
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