Neuronal Ceroid Lipofuscinoses (NCL) are a group of inherited neurodegenerative disorders with lysosomal pathology (CLN1-14). Recently, mutations in the DNAJC5/CLN4 gene, which encodes the presynaptic co-chaperone CSP were shown to cause autosomal-dominant NCL. Although 14 NCL genes have been identified, it is unknown if they act in common disease pathways. Here we show that two disease-associated proteins, CSPα and the depalmitoylating enzyme palmitoyl-protein thioesterase 1 (PPT1/CLN1) are biochemically linked. We find that in DNAJC5/CLN4 patient brains, PPT1 is massively increased and mis-localized. Surprisingly, the specific enzymatic activity of PPT1 is dramatically reduced. Notably, we demonstrate that CSP is depalmitoylated by PPT1 and hence its substrate. To determine the consequences of PPT1 accumulation, we compared the palmitomes from control and DNAJC5/CLN4 patient brains by quantitative proteomics. We discovered global changes in protein palmitoylation, mainly involving lysosomal and synaptic proteins. Our findings establish a functional link between two forms of NCL and serve as a springboard for investigations of NCL disease pathways.

The autosomal dominant neuronal ceroid lipofuscinoses (NCL) CLN4 is caused by mutations in the synaptic vesicle (SV) protein CSPα. We developed animal models of CLN4 by expressing CLN4 mutant human CSPα (hCSPα) in Drosophila neurons. Similar to patients, CLN4 mutations induced excessive oligomerization of hCSPα and premature lethality in a dose-dependent manner. Instead of being localized to SVs, most CLN4 mutant hCSPα accumulated abnormally, and co-localized with ubiquitinated proteins and the prelysosomal markers HRS and LAMP1. Ultrastructural examination revealed frequent abnormal membrane structures in axons and neuronal somata. The lethality, oligomerization and prelysosomal accumulation induced by CLN4 mutations was attenuated by reducing endogenous wild type (WT) dCSP levels and enhanced by increasing WT levels. Furthermore, reducing the gene dosage of Hsc70 also attenuated CLN4 phenotypes. Taken together, we suggest that CLN4 alleles resemble dominant hypermorphic gain of function mutations that drive excessive oligomerization and impair membrane trafficking.

Based on the analysis of the basic principle of traditional inertial navigation technology, this paper puts forward a kind of simplified model of the track measurement which applies to underground pipeline. The model using structures of half-strap-down stable platform that composes of a single axis gyro, two accelerometers and pulse taximeter, by measuring angular velocity of pipeline azimuth, pitching angle, platform rolling angle and pipeline length, combined with self-actuated research space track, work out the mathematics model, eventually work out the space track of the underground pipeline. The experiment proves that the underground pipeline track measurement instrument which is designed based on the simplified model, can meet the accuracy requirement of the no-dig project on track measurement, and the equipment’s operation is stable and reliable.

A new type of small concrete blocks with high strength performance was generated in this study, and the main component of this kind of small blocks were made by the MU15.0 that was extracted from the waste rock chips. The effect of content of stone powder and the different curing methods on the shrinkage of the proposed concrete blocks, was investigated by using the experimental method. The results showed that (i) with the increase of the amount of stone power, the drying shrinkage of rock chips concrete went up at first, and then the opposite change was generated; (ii) The small hollow blocks made by the rock chips concrete after steam curing kiln, under the condition of enough water curing and seal environment, had higher compressive strength and smaller shrinkage comparing with other curing methods.

This paper presents an experimental study on the permeability and the pore structure of lightweight concrete with fly ash, zeolite powder, or silica fume, in comparison to that of normal weight aggregate concrete. The results showed that the mineral admixtures can improve the anti-permeability performance of lightweight aggregate concrete, and mixed with compound mineral admixtures further more. The resistance to chloride-ion permeability of light weight concrete was higher than that of At the same strength grade, the anti-permeability performance of lightweight aggregate concrete is better than that of normal weight aggregate concrete. The anti-permeability performance of LC40 was similar to that of C60. Mineral admixtures can obviously improve the pore structure of lightweight aggregate concrete, the total porosity reduced while the pore size decreased.

Abstract. Structural health monitoring of concrete infrastructures has attracted enormous attention due to the brittle nature of concrete. In this research, we report the carbon fibre/silicon rubber composite sensors and their excellent monitoring in concrete's compression. It is shown that the electric resistance change synchronously with the mechanical deformation of concrete during the compression process. With the increase of carbon fibre fraction, the sensitivity decreases and the numerical equations to predict the structural change are also obtained. The experimental results reported here highlight the potential application of CF/silicon composites as an effective, real-time structural monitoring sensor with low-cost and long life.

Abstract:It is more and more general of using industrial solid waste as the aggregates in construction materials for non-structural applications. But because of the developments and applications of reinforced blocks masonry structure in the modern masonry structure, especially in the mid-high and high storey buildings, there will be a growing interest of using industrial solid waste to produce high strength concrete small hollow blocks for structural applications. This experiment by mixing the different proportions of rock chips within the range of 30-70% as the replacement for sand prepared high strength concrete small hollow blocks which the compressive grade is MU 15.0, the influence of aggregates grading on the compressive strength of high strength concrete small hollow blocks was investigated at the same water/cement (w/c) ratio (0.45). In addition, the influence of the different curing methods on the compressive strength and shrinkage of high strength concrete small hollow blocks were also investigated, test results showed that high strength concrete small hollow blocks under the curing method which is the one-time pouring the ample amount of water, covered and sealed with plastic sheeting, the compressive strength had a better development, and the total shrinkage was larger than others. IntroductionThere will be a big development of Chinese housing construction in the future for a long period of time, which requires the construction industry must be according with sustainable development strategy, break the routine, develop the new wall materials [1]. Since "Eleventh Five-Year Plan", the new building materials based on the building energy efficiency had a rapid development, the using of which played a "four of a green" objectives in the building structure [2]. The foreign researchers [3,4] studied that the replacement of coarse and fine natural aggregates by recycled aggregates at the suitable levels had little effect on the compressive strength of the blocks, based on the laboratory work, factory trials showed that there were no practical problems with the use of recycled demolition aggregate in the manufacture of building blocks. Some domestic scholars [5][6][7] using industrial waste such as iron-tailings, steel slag, and gangue prepared the MU10.0 load-bearing concrete hollow blocks, which resulted in a good economic and social benefits. However, the study of preparing high strength concrete small hollow blocks more than MU15.0 and 45 percent hole rate with industrial waste is more lesser.Concrete small hollow blocks are non-sintering prepared with a certain percentage gelled materials and aggregates by mechanical forming and curing, which performances are influenced by the changes of ambient temperature and humidity. In the former block masonry structure applications, the practical strength less than the design strength resulted the problems of missing edge off angle and cracks in walls, which even seriously affected the quality of the engineering, so how to ensure the excellent performances of concr...