Development of Phosphodiesterase–Protein-Kinase Complexes as Novel Targets for Discovery of Inhibitors with Enhanced Specificity

Phosphodiesterases (PDEs) hydrolyze cyclic nucleotides to modulate multiple signaling events in cells. PDEs are recognized to actively associate with cyclic nucleotide receptors (protein kinases, PKs) in larger macromolecular assemblies referred to as signalosomes. Complexation of PDEs with PKs generates an expanded active site that enhances PDE activity. This facilitates signalosome-associated PDEs to preferentially catalyze active hydrolysis of cyclic nucleotides bound to PKs and aid in signal termination. PDEs are important drug targets, and current strategies for inhibitor discovery are based entirely on targeting conserved PDE catalytic domains. This often results in inhibitors with cross-reactivity amongst closely related PDEs and attendant unwanted side effects. Here, our approach targeted PDE–PK complexes as they would occur in signalosomes, thereby offering greater specificity. Our developed fluorescence polarization assay was adapted to identify inhibitors that block cyclic nucleotide pockets in PDE–PK complexes in one mode and disrupt protein-protein interactions between PDEs and PKs in a second mode. We tested this approach with three different systems—cAMP-specific PDE8–PKAR, cGMP-specific PDE5–PKG, and dual-specificity RegA–R_D complexes—and ranked inhibitors according to their inhibition potency. Targeting PDE–PK complexes offers biochemical tools for describing the exquisite specificity of cyclic nucleotide signaling networks in cells.     

导管架平台上部组块双船拆除

为研究复杂海域环境中海洋平台双船拆除方法的安全性与可操作性,采用水动力数值计算与水池模型试验相结合的方法进行研究。将双船水动力耦合计算与水池模型试验进行对比,在相对理想海况下,结合与实际工况接近的规则波作用,进行驳船水动力性能变化与运动响应的幅值分析。在受力分析方面,对甲板耦合装置进行改良设计,对比试验数据与数值计算数据,得到受力在合理范围内的结论。研究内容为实际施工的合理性提出一定的指导性意见。     

A novel fabrication procedure for producing high strength hydroxyapatite ceramic scaffolds with high porosity

Hydroxyapatite (HA) scaffolds were fabricated using the space holder method with a pressureless sintering process in a systematically developed manner at different fabrication stages to increase the strength of the scaffold at high porosity. Polyvinyl alcohol (PVA) and Polymethyl methacrylate (PMMA) were used as binders and space holder agents, respectively. The physical properties of the HA scaffolds were characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), linear shrinkage test, and porosity measurements. The mechanical properties of the HA scaffolds were analyzed using compressive strength measurements. The results revealed that the HA scaffold met the expected quality requirements with a compressive strength of 2.2 MPa at a porosity of 65.6% with pore sizes distributed in the range of 126–385 μm. The shrinkage of the scaffold diameter occurred by 20.27%, this diameter shrinkage predominantly to the shrinkage of the HA scaffold caused by sintering. Besides, suspect that a higher PMMA concentration causes pore size shrinkage upon sintering. The formation of pore interconnections was evidenced by SEM observations and the ‘translucent light method’ developed in this study. The results of the scaffold phase test using XRD showed that the final scaffold consisted only of the HA phase, as the PVA and PMMA phases burned out during the sintering process.     

给水管道腐蚀原因及防护措施探讨

给水管道在使用过程中很容易受到人为外力、管道材质、地下水、周围空气、土壤等因素的影响而腐蚀,影响了管道的使用质量和寿命,也带来较大的安全隐患。本文主要是从给水管道腐蚀原因出发,并探讨防护措施。     

Spectral radiance reconstruction from trichromatic camera responses based on orthogonal test and regularized algorithm

Reconstruction of spectral information based on multi‐channel image system is a significant problem in color reproduction, detection, and recognition. A spectral radiance reconstruction from trichromatic digital camera responses is researched in this article. The mapping relationship between the trichromatic imaging system response and the incident spectral radiance is analyzed. Then, in order to remove the ill‐posedness of the problem, a regularized constraint solution model of spectral radiance reconstruction matrix is established. And the spectral radiance can be reconstructed by spectral radiance reconstruction matrices and trichromatic imaging system response. Finally, the spectral radiance reconstruction matrix is estimated by the system radiometric calibration experiment. The input radiance is offered by a LCD display. A 3‐factor and 9‐level orthogonal test is designed for the calibration experiment, and a test set of 24 colors is used for precision analysis. The results show that the average relative mean error of our method is 8.69%, it is lower than that of Wiener filtering method by 2.84%. The method can reconstruct spectral radiance information effectively.     

Notwendigkeit und Vermarktung von Flexibilitätsoptionen im Energiesystem der Zukunft

Demands on production, distribution and consumption of electrical energy change fundamentally with the energy revolution. Energy purchasing costs for inflexible consumers are rising and proceeds of inflexible producers are sinking. Companies are able to reduce costs by marketing operational flexibility options. This article sets out the need of flexibility in the energy system and the new marketing options. Flexibility potentials within infrastructure plants of a chemical park are analyzed, evaluated regarding marketing and activated in the presented research project FlexChemistry.     

涪陵地区茅三段热液白云岩展布影响因素分析

针对热液白云岩展布非均质性强的问题,开展基底断裂与茅三段沉积演化关系研究,分析断裂样式与白云岩分布关系,建立沉积演化模式,预测白云岩的分布。研究结果表明:茅三段可划分为5个小层,1~3小层为白云岩发育主要时期,4~5小层为台地均一化时期,不发育白云岩;15-1、15-2和16号基底断裂控制了早期“台-洼”相间的沉积地貌,断裂附近的地貌高部位为生屑滩发育有利部位,为白云岩的发育提供物质基础;15-1、15-2号基底断裂样式为花状,周边生屑滩白云石化程度高,为白云岩发育最有利区;16号基底断裂为直立状,附近白云石化发育程度较低,为白云岩发育较有利区。研究成果可为热液白云岩领域的进一步勘探提供指导依据。     

Sizing of multi-stage Op Amps by combining design equations with the gm/ID method

Analog integrated circuit design has as integral parts both analytical reasoning and numerical validation in the process from topology construction to sizing. Given a circuit topology, different circuit sizing results can be obtained from different processes of sizing inference. Sizing methods by simulation-based numerical searching have been a continuously studied subject. However, almost all approaches in this category require an overwhelming number of circuit simulations to arrive at an optimized sizing result. On the other hand, many published manual sizing methods by using the conventional device equations also require repeated SPICE simulations to correct the equation-based sizing results. This paper proposes a systematic gm/ID-based initial sizing method specifically customized for designing multiple-stage operational amplifiers (Op Amps). A main feature of the proposal is to use circuit-level design equations as constraints on the gm/ID table lookup method to substantially reduce the uncertainty in the sizing calculations. As a result, a significant amount of SPICE based correction work can be reduced to complete an initial sizing. The proposed sizing procedure includes a few regular sizing rules customized to the configuration of multi-stage Op Amps. We validate the proposed sizing method by application to several multi-stage Op Amp examples with a capacitive load or Miller compensation. Simulations have justified that the produced initial sizing results can achieve most of the prespecified design targets.     

浅渍法发酵豇豆的工艺优化

以具有降解亚硝酸盐功能的植物乳杆菌（Lactobacillus plantarum）SD-7和具有优良抗氧化能力的植物乳杆菌（Lactobacillus plantarum）FM-LP-9为复合发酵剂（1∶1），采用浅渍法发酵豇豆。以硬度和感官评分为考察指标，通过单因素试验及响应面试验研究复合发酵剂接种量、发酵温度和发酵时间对浅渍法发酵豇豆品质的影响。结果表明，最佳发酵工艺条件为发酵温度25 ℃，接种量5%，发酵时间125 h，在此优化条件下，得到的浅渍法发酵豇豆硬度为47.31 N，感官评分为90.98分，香气浓郁、口感脆嫩。