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Background Escherichia fergusonii is a rare opportunistic pathogen in humans and animals, especially with biofilm. Methods In one case, E. fergusonii with biofilm was detected in the bile, and silver staining was used to prove it had biofilm. The clinical characteristics and drug susceptibility of eight cases of E. fergusonii retrieved from the literature were also summarized. Results This is a case of E. fergusonii with biofilm, which has not been reported in China. The 8 cases retrieved from the literature did not specify whether they had biofilm, but we analyzed their clinical characteristics and drug susceptibility. All patients were treated with antimicrobial drugs. 8 cases showed sensitivity to piperacillin/tazobactam and imipenem in 6 cases (75%), but poor sensitivity to levofloxacin and ciprofloxacin. Conclusion The silver staining method proved biofilm in this case, which is the first case of E. fergusonii with biofilm in China.

Overactivation of N-methyl-D-aspartate receptor (NMDAR) in the spinal cord dorsal horn (SDH) in the setting of injury represents a key mechanism of neuropathic pain. However, directly blocking NMDAR or its downstream signaling, interaction between postsynaptic density-95 (PSD-95) and neuronal nitric oxide synthase (nNOS), causes analgesic tolerance, mainly due to GABAergic disinhibition. The aim of this study is to explore the possibility of preventing analgesic tolerance through co-targeting NMDAR downstream signaling and γ-aminobutyric acid type A receptors (GABAARs). Methods: Mechanical/thermal hyperalgesia were quantified to assess analgesic effects. Miniature postsynaptic currents were tested by patch-clamp recording to evaluate synaptic transmission in the SDH. GABA-evoked currents were tested on HEK293 cells expressing different subtypes of recombinant GABAARs to assess the selectivity of (+)-borneol and ZL006-05. The expression of α2 and α3 subunits of GABAARs and BDNF, and nNOS-PSD-95 complex levels were analyzed by western blotting and coimmunoprecipitation respectively. Open field test, rotarod test and Morris water maze task were conducted to evaluate the side-effect of ZL006-05. Results: (+)-Borneol selectively potentiated α2- and α3-containing GABAARs and prevented the disinhibition of laminae I excitatory neurons in the SDH and analgesic tolerance caused by chronic use of ZL006, a nNOS-PSD-95 blocker. A dual-target compound ZL006-05 produced by linking ZL006 and (+)-borneol through an ester bond blocked nNOS-PSD-95 interaction and potentiated α2-containing GABAAR selectively. Chronic use of ZL006-05 did not produce analgesic tolerance and unwanted side effects. Conclusion: By targeting nNOS-PSD-95 interaction and α2-containing GABAAR simultaneously, chronic use of ZL006-05 can avoid analgesic tolerance and unwanted side effects. Therefore, we offer a novel candidate drug without analgesic tolerance for treating neuropathic pain.

This brief presents a 2 $\times $ VDD output buffer using the encoded compensation technique to minimize slew rate (SR) deviation caused by PVT (process, voltage, temperature) variations. The process detectors can both detect all five process corners and ensure the compensation code unchanged in VT variations. Besides, the charging paths of the proposed voltage level converter (VLC) are independent and directly driven by logic gate, which applied in output stage to speed output buffer data rate up. The proposed design is implemented using a typical 90 nm 1.2 V 1P9M CMOS process, where the core area of a single output buffer is $400\,\,\mu \text{m}\times 56\,\,\mu \text{m}$ . The measured maximum data rate is 640/480 MHz given 1.2/2.5 V supply voltage, and the power consumption is 32.2 mW at 640 MHz data rate. the slew rate variation improvement is 41.5%/41.9% by PVT detection and SR compensation for VDDIO=1.2/2.5 V, respectively.

The application of magnetic fields, electric fields, and the increase of the electromagnetic wave frequency are up-and-coming solutions for the blackout problem. Therefore, this study considers the influence of the external magnetic field on the electron flow and the effect of the external electric field on the electron density distribution, and uses the scattering matrix method (SMM) to perform theoretical calculations and analyze the transmission behavior of terahertz waves under different electron densities, magnetic field distributions, and collision frequencies. The results show that the external magnetic field can improve the transmission of terahertz waves at the low-frequency end. Magnetizing the plasma from the direction perpendicular to the incident path can optimize the right-hand polarized wave transmission. The external electric field can increase the transmittance to some extent, and the increase of the collision frequency can suppress the right-hand polarized wave cyclotron resonance caused by the external magnetic field. By adjusting these parameters, it is expected to alleviate the blackout phenomenon to a certain extent.

We propose a cylindrical conformal transmitted metasurface for orbital angular momentum vortex wave generation. Formulas for calculating the phase distributions of cylindrical conformal transmitted metasurface is presented. A prototype of the proposed conformal transmitted metasurface is designed, fabricated and measured. Measured results shows that the proposed conformal transmitted metasurface can effectively generate vortex waves, which verifies the effectiveness of our method. The proposed method may pave the way of vortex wave generation with cylindrical conformal devices.

The discovery of mammalian target of rapamycin (mTOR) kinase inhibitors has always been a research hotspot of antitumor drugs. Consensus scoring used in the docking study of mTOR kinase inhibitors usually improves hit rate of virtual screening. Herein, we attempt to build a series of consensus scoring models based on a set of the common scoring functions. In this paper, twenty-five kinds of mTOR inhibitors (16 clinical candidate compounds and 9 promising preclinical compounds) are carefully collected, and selected for the molecular docking study used by the Glide docking programs within the standard precise (SP) mode. The predicted poses of these ligands are saved, and revaluated by twenty-six available scoring functions, respectively. Subsequently, consensus scoring models are trained based on the obtained rescoring results by the partial least squares (PLS) method, and validated by Leave-one-out (LOO) method. In addition, three kinds of ligand efficiency indices (BEI, SEI, and LLE) instead of pIC50 as the activity could greatly improve the statistical quality of build models. Two best calculated models 10 and 22 using the same BEI indice have following statistical parameters, respectively: for model 10, training set R2 = 0.767, Q2 = 0.647, RMSE = 0.024, and for test set R2 = 0.932, RMSE = 0.026; for model 22, raining set R2 = 0.790, Q2 = 0.627, RMSE = 0.023, and for test set R2 = 0.955, RMSE = 0.020. These two consensus scoring model would be used for the docking virtual screening of novel mTOR inhibitors.

Summary Notch signaling is critically involved in neural development, but the downstream effectors remain incompletely understood. In this study, we cultured neurospheres from Nestin-Cre-mediated conditional Rbp-j knockout (Rbp-j cKO) and control embryos and compared their miRNA expression profiles using microarray. Among differentially expressed miRNAs, miR-342-5p showed upregulated expression as Notch signaling was genetically or pharmaceutically interrupted. Consistently, the promoter of the miR-342-5p host gene, the Ena-vasodilator stimulated phosphoprotein-like (Evl), was negatively regulated by Notch signaling, probably through HES5. Transfection of miR-342-5p promoted the differentiation of neural stem cells (NSCs) into intermediate neural progenitors (INPs) in vitro and reduced the stemness of NSCs in vivo. Furthermore, miR-342-5p inhibited the differentiation of neural stem/intermediate progenitor cells into astrocytes, likely mediated by targeting GFAP directly. Our results indicated that miR-342-5p could function as a downstream effector of Notch signaling to regulate the differentiation of NSCs into INPs and astrocytes commitment., Graphical Abstract, Highlights • miR-342-5p acts as a downstream effector of canonical Notch signaling • Notch signal inhibits miR-342-5p expression by regulating its host gene Evl • miR-342-5p promotes the transition of NSCs into INPs • Astrocyte commitment was suppressed by miR-342-5p targeting GFAP, In this article, Han and colleagues show that miR-342-5p acts as a downstream effector of Notch signaling in the mouse CNS. Notch signal inhibits miR-342-5p expression by regulating its host gene Evl. And with attenuated Notch signal in NSCs, miR-342-5p is upregulated to promote NSCs transition into INPs, and to inhibit astrocyte commitment by targeting GFAP.

(+)-Borneol, a bicyclic monoterpene, has been shown to possess valuable biological properties and potential as a pharmaceutical agent due to anti-inflammatory, anti-oxidant and GABA receptor-enhancing functions; it also enhances the permeability of the blood brain barrier to improve the efficacy of CNS drugs. In this study, we have developed a simple, selective, and rapid liquid chromatography-tandem mass spectrometry method for the assay of (+)-borneol in rat plasma. Verapamil was used as an internal standard. Plasma samples were deproteinized using methanol. The analyte was detected by a mass spectrometer with positive atmospheric pressure chemical ionization by multiple reaction monitoring mode for transitions at m/z [M + H]+ 137.2 → 81.0 for (+)-borneol and 455.2 → 165.1 for verapamil. The method has been fully validated to ensure good selectivity, a satisfactory lower limit of quantification at 10.0 ng/mL, acceptable intra- and inter-day accuracy, and high precision. The method was used for the pharmacokinetic evaluation of (+)-borneol in Sprague-Dawley rats after intravenous, oral, and sublingual administration. The results indicate that oral bioavailability of (+)-borneol was extremely low but sublingual administration yielded rapid absorption and favorable bioavailability of (+)-borneol.

In this paper, we studied the positive integer solutions of a typical Diophantine equation starting from two basic equations including a Diophantine equation and a Pell equation, and we will prove all the positive integer solutions of the typical Diophantine equation.

In this paper, we studied the integer solutions of the typical Diophantine equations with some important theories in quadratic fields and the fundamental theorem of arithmetic in the ring of quadratic algebraic integers. We proved all the integer solutions of the Diophantine equation Χ2 − 21 = 4y5.

By observing that the infinite triangle obtained from some generalized harmonic numbers follows a Riordan array, we using connections between the Stirling numbers of both kinds and other inverse generalized harmonic numbers. we proved some combinatorial sums and inverse generalized harmonic number identities.

High speed encoder is the key element of high speed analog-to-digital converter (ADC). Therefor the type of encoder, the type of code, bubble error suppression and bit synchronization must be taken into careful consideration especially for folding and interpolating ADC. To reduce the bubble error which may resulted from the circuit niose, comparator metastability and other interference, the output of quantizer is first encoded with gray code and then converted to binary code. This high speed encoder is verified in the whole time-interleaved ADC with 0.18 Bi-CMOS technology, the whole ADC can achieve a SNR of 45 dB at the sampling rate of 5GHz and input frequency of 495MHz, meanwhile a bit error rate (BER) of less than 10-16 is ensured by this design.

A structure of ADCs which combines fold-interpolation and pipeline is introduced, as well as corresponding digital calibration method. The simulation shows that the performances of the ADC after calibration are improved a lot. The SFDR achieves 62dB at a sampling rate of 800MHz, when the input analog signal is at 397MHz.

In this paper, we present an 8-bit 5 Gsample/s time-interleaved analog-to-digital converter (TI ADC). A 4-phase low jitter clock is designed to control four 1.25 Gsample/s sub-ADCs which is implemented using folding and interpolating architecture. Digital calibration is used to adjust the offset error and gain error of sub-ADCs. Meanwhile, serial peripheral interface (SPI) is adopted to adjust mismatch of gain and sample time between sub-ADCs. The whole TI ADC is designed using a 0.18m SiGe BiCMOS process. The whole ADC has a SNR of about 45 dB at the input frequency of 495 MHZ and an equivalent ENOB of 7.2 bits.

A high speed open-loop track/hold circuit in 0.18um CMOS process is presented. Open-loop and differential architecture are adopted to obtain high bandwidth and high speed;time-interleaved structure is used to reach a high sampling rate;source negative feedback and offset compensation are used to improve the linearity of the circuit.Simulation results show that with 396.875MHz input, 1.6GSPS sampling rate, driving the pre-amplifier of ADC, the thack/hold circuits SFDR(spurious-free dynamic range) is 75.8dB,satisfying the demand of 12 bits ADC.The circuit features high sampling rate,wide bandwidth,high SFDR and universal.

It is regarded that the magmatic activity is over in Upper Hercynides and become stable platform in Mesozoic era in the Shanshan county, Xinjiang province, China. According to the regional geology investigation , rhyolitic porphyry and porphyry granite are broken out. Based on the analysis of rock petrology features, petrochemistry, geochemistry, the latest researches of formation and isotope dating results, it is believed that intrusion is formed in cretaceous period and is the result of Yanshan movement.

In this paper, we introduce a value chain approach, on the view of the value chain analytic in business management, to be the framework of a crisis response system serving for crisis management strategy in identifying risk sources, responding to unexpected events, and recovering from a shock. This system is not only a computer system but also a system of governmental emergency response mechanism and it is tremendous and complex. The system integrates and coordinates the correlative resources of emergency response units of the city. We consider the efficiency of the system. In addition, the run cost of the system also is taken into account. Based on this framework, the Qingdao’s practical situation is analyzed. As a result, a design proposal of the Qingdao’s crisis response system is put forward.

Measuring liquid level with high accuracy is an urgent requirement. This paper mainly focus on the demodulation system of fiber-optic liquid level sensor based on Fabry-Perot cavity, design and simulate the demodulation system by the single-chip simulation software.

A high-speed 8-bit analog-to-digital converter in 0.35µm BiCMOS process technology is presented. The ADC uses the unique folding and interpolating architecture and the dual-channel timing interleave multiplexing technology to achieve a sampling rate of 2GSPS. In case of digital calibration, as a result of testing, the ADC achieves 7.32ENOB at analog input of 484MHz, and 7.1ENOB at Nyquist input after the chip is self-corrected.

This paper presents a practical design procedure for hairpin-line filter using MgB2 superconducting films. The design process starts with the theoretical design of the filter. An optimization of design is achieved using Advanced Design System (ADS). Finally, the results of the simulation of the design are presented.

Notch signaling is critical for multiple aspects of neurogenesis, but how it regulates the proliferation and differentiation of neural stem cells (NSCs) and intermediate neural progenitors (INPs) has not been well elucidated, especially in vivo. In this study, we conditionally ablated the transcription factor RBP-J, which mediates signaling from all four mammalian Notch receptors, in the basal forebrain and ventral midbrain using the RBP-J-floxed mouse and a newly established Nestin-Cre mouse. We found that at early stage of neurogenesis (E11.5), the frequency of neurospheres increased significantly in the RBP-J-inactivated regions. The majority of the RBP-J deficient neurospheres were composed of INPs, suggesting the precocious differentiation of NSCs into INPs. Meanwhile, neuronal differentiation was reduced in the same regions at E11.5, inconsistent with the precocious differentiation phenotype in most Notch-related mutants. At late neurogenic stages (E17.5 and neonatal), as expected from precociously exhausted NSC pool, neurosphere frequency and NSCs decreased in the RBP-J-ablated regions, accompanied by a significant increase of both neurons and glial cells. These results indicated that the RBP-J-mediated signaling might inhibit the differentiation of NSCs into INPs and support the generation of certain early born neurons at early neurogenic stages.