Role and mechanism of action of leucine-rich repeat kinase 1 in bone

Leucine-rich repeat kinase 1 （LRRK1） plays a critical role in regulating cytoskeletal organization, osteoclast activity, and bone resorption with little effect on bone formation parameters. Deficiency of Lrrkl in mice causes a severe osteopetrosis in the metaphysis of the long bones and vertebrae bones, which makes LRRK1 an attractive alternative drug target for the treatment of osteoporosis and other high-turnover bone diseases. This review recent advances on the functions of the Lrrkl-related family members, Lrrkl deficiency-induced skeletal phenotypes, LRRK1 structure-function, potential biological substrates and interacting proteins, and the mechanisms of LRRK1 action in osteoclasts.

Influence of Repeated Variable Load on Long-Term Behavior of Concrete Elements

The objective of this paper is to study the influence of repeated variable action on long-term behavior of concrete structural elements using quasi-permanent combination of actions, for the assessment of long-term effects （e.g., effects due to creep and shrinkage in concrete structures）, as it is proposed in Eurocodes. Extensive experimental program and analytical research using model B3 and AAEM （age adjusted effective modulus） method was performed in order to define quasi-permanent factor ψ2, for two specific loading histories. These loading histories were consist of long-term permanent action ＂G＂ and repeated variable action ＂Q＂. The variable load was applied in cycles of loading/unloading for 24 h and 48 h in period of 400 days appropriately for one series of concrete elements. 24 reinforced concrete beams, dimensions 150 mm × 280 mm × 3,000 mm, were tested. Twelve beams were made of concrete class C30/37 and 12 of concrete class C60/75.

Performance Degradation of the Repeated Recycled Aggregate Concrete with 70% Replacement of Three-generation Recycled Coarse Aggregate

The feasibility of using different generations recycled coarse aggregate（RCA） on structural concrete was fully evaluated by studying the performance of the recycled coarse aggregates and their corresponding concretes, the different generations of RCA were recycled by following the repeated mode of ‘concrete-waste concrete-coarse aggregate-concrete＇. Moreover, the focus was on ‘three generations＇ of repeated RCAs, the RCA was produced by crushing and regenerating the artificial accelerated degraded concrete, the process was designed to follow the nature degradation of the concrete with a coupling action of accelerated carbonation and bending load. The properties of x-generation（x=1, 2 or 3） of repeated RCA were systematically investigated and the compressive and splitting tensile strengths of relating structural concretes（with 70% replacement of x-generation of RCA） were studied accordingly. The results show a competent compressive and splitting tensile strength of 30 MPa at 28 th day of structural concretes with all generations of repeated RAC. And the gradual degraded performance of the repeated RCAs was observed with an increased numbers of repetition（1〉2〉3 generations）, the overall performances of all repeated RCAs fulfill the Class Ⅲ according to Chinese Standards GB25177-2010. Our gained insight demonstrates a feasibility of using at least 3 generations of repeated RCA for the production of normal structural concrete.