Identification of novel mutations in Chinese Hans with autosomal dominant polycystic kidney disease

<p>Abstract</p> <p>Background</p> <p>Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited renal disease with an incidence of 1 in 400 to 1000. The disease is genetically heterogeneous, with two genes identified: <it>PKD1 </it>(16p13.3) and <it>PKD2 </it>(4q21). Molecular diagnosis of the disease in at-risk individuals is complicated due to the structural complexity of <it>PKD1 </it>gene and the high diversity of the mutations. This study is the first systematic ADPKD mutation analysis of both <it>PKD1 </it>and <it>PKD2 </it>genes in Chinese patients using denaturing high-performance liquid chromatography (DHPLC).</p> <p>Methods</p> <p>Both <it>PKD1 </it>and <it>PKD2 </it>genes were mutation screened in each proband from 65 families using DHPLC followed by DNA sequencing. Novel variations found in the probands were checked in their family members available and 100 unrelated normal controls. Then the pathogenic potential of the variations of unknown significance was examined by evolutionary comparison, effects of amino acid substitutions on protein structure, and effects of splice site alterations using online mutation prediction resources.</p> <p>Results</p> <p>A total of 92 variations were identified, including 27 reported previously. Definitely pathogenic mutations (ten frameshift, ten nonsense, two splicing defects and one duplication) were identified in 28 families, and probably pathogenic mutations were found in an additional six families, giving a total detection level of 52.3% (34/65). About 69% (20/29) of the mutations are first reported with a recurrent mutation rate of 31%.</p> <p>Conclusions</p> <p>Mutation study of <it>PKD1 </it>and <it>PKD2 </it>genes in Chinese Hans with ADPKD may contribute to a better understanding of the genetic diversity between different ethnic groups and enrich the mutation database. Besides, evaluating the pathogenic potential of novel variations should also facilitate the clinical diagnosis and genetic counseling of the disease.</p

Surface metallization of solid lubricants and its effect on the mechanical properties of Fe-based bit matrix

Self-lubricating impregnated diamond bit can provide a new technical solution to the lunar drilling problem, but the poor wettability between the solid lubricants and the bit matrix can lead to degradation of physical and mechanical properties of the bit matrix. The influence of properties of the solid lubricant MOS2, WS2 and CAF2 on the electroless plating was studied, and the influence of the solid lubricant coating on the indentation hardness and bending strength of the bit matrix was investigated. The results show that the surface nickel plating of the above three solid lubricants can be achieved by the chemical plating method, but there are some differences in their plating appearances. Under the same volume concentration of condition, MoS2 and WS2 surface metallization can improve the mechanical properties of self-lubricating impregnated diamond bit matrix, but the effect of CaF2 is insignificant

Efficient Defense Decision-Making Approach for Multistep Attacks Based on the Attack Graph and Game Theory

In the multistep attack scenario, each rational attack-defense player tries to maximize his payoff, but the uncertainty about his adversary prevents him from taking the favorable actions. How to select the best strategy from the candidate strategies to maximize the defense payoff becomes the core issue. For this purpose, the paper innovatively designs a game theory model from the point of network survivability in combination with the attribute attack graph. The attack graph is created based on the network connectivity and known vulnerabilities using the MulVAL toolkit, which gives the full view of all the known vulnerabilities and their interdependence. Then, we use the attack graph to extract attack-defense actions, candidate attack-defense strategies, attack-defense payoffs, and network states, as well as other game modeling elements. Afterwards, the payoffs of attack-defense strategies are quantified by integrating attack-defense strength and network survivability. In addition, we input the above elements into the game model. Through repeated learning, deduction, and improvement, we can optimize the layout of defense strategies. Finally, the efficient strategy selection approach is designed on the tradeoff between defense cost and benefit. The simulation of attack-defense confrontation in small-scale LAN shows that the proposed approach is reliable and effective

The Crystallization Behavior of TiO2-CaO-SiO2-Al2O3-MgO Pentabasic Slag with a Basicity of 1.1–1.4

The utilization of titanium-containing blast furnace slag has been an unsolved problem for a long time. Failure to make effective use of the slag, which is caused by a high TiO2 content within it, not only results in a waste of resources, especially titanium, but also increases environmental risk. The key to address the problem is the enrichment and extraction of TiO2 from the slag first. Therefore, in order to study the enrichment of titanium, the crystallization behavior of TiO2-CaO-SiO2-Al2O3-MgO pentabasic slag, the main compositions of titanium-containing blast furnace slag, within the basicity range of 1.1–1.4 was investigated theoretically and experimentally. Thermodynamic calculation shows that perovskite is the main titanium-containing phase and titanium can be enriched in perovskite. By decreasing the temperature, perovskite precipitates at first. Additionally, with the increase of basicity, perovskite precipitation temperature increases continuously, and its amount of precipitation almost does not change, while the amounts of other phases change obviously. The experimental results demonstrate similar results except for the amount of perovskite (with the increase of basicity, perovskite precipitation amount increases slightly), caused by kinetic reason. In addition, the morphology of the slag at different scales was observed. The surface of the cooled slag is granular, vein-like, and irregular, multilaterally shaped from outside to inside. The crystal is dendritic with a spine-like trunk, and the edge is blade-like. In terms of the structure of the crystal, the inner part of it is perovskite, and the outer part is covered with a layer of other phases with spinel inlaying it. Finally, the precipitated mechanism is proposed as well

Influence of notch root radius on high cycle fatigue properties and fatigue crack initiation behavior of Ti-55531 alloy with a multilevel lamellar microstructure

Notch high cycle fatigue (HCF) properties and microcrack initiation behavior of Ti-55531 alloy with a multilevel lamellar microstructure under various notch radii were systematically investigated. Results indicate that the reduction of notch root radius significantly promotes fatigue microcrack initiation, and then dramatically reduces the HCF life and strength of the alloy. Cyclic deformation of the alloy is mainly controlled by the slipping and deformation twinning in α plates. The primary fatigue crack initiation micro-mechanism is α/β interface cracking induced by slipping and twinning at all notch HCF specimens. Moreover, the volume fraction of twinning would increase with decreasing of the notch root radius. Interestingly, when the notch root radius is the smallest (R = 0.14 mm) and the stress concentration factor is the largest (Kt = 4), in addition to slipping and twinning, basal stacking faults promoting the cracking of α/β interface could be another crucial HCF microcrack initiation mechanism of the alloy. Furthermore, with decreasing of notch root radius and increasing of stress concentration factor, the size of cycle plastic deformation zone at notch root gradually reduces to the size of α colony and even the α plate. Therefore, the order of influential degree of three different levels microstructure on the crack initiation mechanism of notched HCF can be arranged as α plate > α colony > β GB

Assessing the utility of visible-to-shortwave infrared reflectance spectroscopy for analysis of soil weathering intensity and paleoclimate reconstruction

Visible-to-shortwave infrared reflectance (VSWIR) spectroscopy is a fast and efficient approach for estimation of soil properties. In order to test whether soil weathering intensity can be predicted using reflectance spectra in the VSWIR range (350-2500 nm), and to examine the efficacy of this methodology to supplement or substitute for traditional mineralogical and geochemical techniques of paleoclimate reconstruction, we investigated a Quaternary soil sequence at Shengli in the Sichuan Basin of southwestern China. VSWIR absorption bands can be characterized by geometrical parameters including position (P), depth (D), width (W), asymmetry (AS), and full width at half maximum (F). Our results indicate that spectral features in the visible-to-near-infrared (VNIR; 350-1000 nm) range can be interpreted in terms of the presence and/or concentration of individual Fe-oxide phases. Spectrally detected water is mostly bound in clay minerals, and this single dominant water source facilitates interpretation of shortwave infrared (SWIR; 1000-2500 nm) parameters. Soil spectral parameters were compared with the Fe-oxide mineralogy, major element composition, and clay mineralogy of soil samples obtained from conventional laboratory analyses. Strong correlations are found between VNIR parameters and Fe-oxide mineralogy, with D-900 serving as the best proxy for total ferric iron concentration. P-900 and D-700/D-500 exhibit similar variation trends and relationships to the hematite/(hematite + goethite) [H/(H + G)] ratio of soil samples, confirming their value as monsoonal weathering intensity proxies. Lower values of P-900 and D-700/D-500 indicate warmer and seasonally drier pedoenvironments, reflecting a stronger East Asian summer monsoon. The utility of some SWIR parameters for assessment of weathering intensity declines in inhomogeneous soils (e.g., those having vermiform structure). Thus, spectral evaluation of weathering intensity is most effective in soils that are relatively homogeneous, for which weathering degree is highly correlated to AS(2200), D-2200/D-1900, and AS(1400). The utility of these spectral proxies depends mainly on the mineral composition of soils and the application type (i.e., laboratory versus field studies). The application of VSWIR in the field (e.g., imaging spectroscopy, or IS) shows promise for rapid, in-situ mapping of weathering intensity, thus providing a convenient approach to paleoclimate reconstruction in remote and inaccessible regions. (C) 2017 Elsevier B.V. All rights reserved