Critical role of ASCT2-mediated amino acid metabolism in promoting leukaemia development and progression

Amino acid (AA) metabolism is involved in diverse cellular functions, including cell survival and growth, however it remains unclear how it regulates normal hematopoiesis versus leukemogenesis. Here, we report that knockout of Slc1a5 (ASCT2), a transporter of neutral AAs, especially glutamine, results in mild to moderate defects in bone marrow and mature blood cell development under steady state conditions. In contrast, constitutive or induced deletion of Slc1a5 decreases leukemia initiation and maintenance driven by the oncogene MLL-AF9 or Pten deficiency. Survival of leukemic mice is prolonged following Slc1a5 deletion, and pharmacological inhibition of ASCT2 also decreases leukemia development and progression in xenograft models of human acute myeloid leukemia. Mechanistically, loss of ASCT2 generates a global effect on cellular metabolism, disrupts leucine influx and mTOR signaling, and induces apoptosis in leukemic cells. Given the substantial difference in reliance on ASCT2-mediated AA metabolism between normal and malignant blood cells, this in vivo study suggests ASCT2 as a promising therapeutic target for the treatment of leukemia

CRISPR/Cas9-mediated genome editing induces exon skipping by alternative splicing or exon deletion

CRISPR is widely used to disrupt gene function by inducing small insertions and deletions. Here, we show that some single-guide RNAs (sgRNAs) can induce exon skipping or large genomic deletions that delete exons. For example, CRISPR-mediated editing of β-catenin exon 3, which encodes an autoinhibitory domain, induces partial skipping of the in-frame exon and nuclear accumulation of β-catenin. A single sgRNA can induce small insertions or deletions that partially alter splicing or unexpected larger deletions that remove exons. Exon skipping adds to the unexpected outcomes that must be accounted for, and perhaps taken advantage of, in CRISPR experiments. Electronic supplementary material The online version of this article (doi:10.1186/s13059-017-1237-8) contains supplementary material, which is available to authorized users

Power system economics course design with energy planning, operation and market cases

The “Power System Economics: Design and Analysis” for students majoring in electrical engineering is a graduate course to teach the basic concepts. The analysis methods and basic concepts of economic problems involved in electric power are of great significance to help students understand the content of economics of electric power system. This paper reforms and redesigns the teaching methods and teaching forms through the combination of curriculum theory and programming practice to improve the innovation and creativity of students. The students could share and show their achievement through their own designs, such as self-designed small games and WeChat small procedures, and the value of this course is greatly enhanced compared to the traditional course

Estimation for torques applied to the master side in a construction robot teleoperation system

The purpose of this research is to develop a method that measures a torque which an operator applies to the joystick without using a torque/force sensor on a joystick. We dealt with a construction robot teleoperation system which is comprised of two joysticks as the master, and an excavator with four degrees of freedom consisting of fork glove, swing, boom, and arm as the slave. It is necessary to know the torque (force) exerted on the master side in force control. Because the joystick does not have a force/torque sensor in our lab, it is not possible to directly obtain the torque. To give prominence to the simple and practical construction robot teleoperation system in our lab, we proposed a method that measures the torque exerted on the joystick to existing equipment. Its effectiveness was verified by a reaction torque experiment

Dynamic Obstacle Detection Based on Background Compensation in Robot’s Movement Space

In the safety area of industrial production, robots are required to have the ability of quickly detecting the dynamic obstacles which appear in the working space of robots when robots move along a predefined route. In order to solve the problem of dynamic obstacles detection more effectively, the paper proposes a quick detection method based on background compensation for dynamic obstacles in robot movement space, which makes extraction of feature points on dynamic obstacles in robot movement space, establishes the background model of optical flow velocity field between adjacent frames and makes background compensation for images with the use of block-matching algorithm in order to realize quick and accurate dynamic obstacles detection in dynamic environment. The experiment results show that the obstacles detection method can effectively eliminate the background movement caused by the movement of camera at the end of robot and can extract a more complete target object. Moreover, it also has good robustness

Estimation for torques applied to the master side in a construction robot teleoperation system

The purpose of this research is to develop a method that measures a torque which an operator applies to the joystick without using a torque/force sensor on a joystick. We dealt with a construction robot teleoperation system which is comprised of two joysticks as the master, and an excavator with four degrees of freedom consisting of fork glove, swing, boom, and arm as the slave. It is necessary to know the torque (force) exerted on the master side in force control. Because the joystick does not have a force/torque sensor in our lab, it is not possible to directly obtain the torque. To give prominence to the simple and practical construction robot teleoperation system in our lab, we proposed a method that measures the torque exerted on the joystick to existing equipment. Its effectiveness was verified by a reaction torque experiment

Application of

In this paper, a technique to determine complicated stress intensity factors on three-dimensional components, which based on the conservation law and the elementary mechanics is proposed, it only needs the geometric relationship between multiple singular stress fields from the crack section, and obtaind the relationship between the stress at different crack tips. In the expression of the stress intensity factor K, K is proportional to the stress σ at the crack tip, and we can get the supplementary equation of between different stress fields K according to the ratio of the stress at the crack tip, then use the J-integral method to calculate the stress intensity factors of different stress fields. In order to verify the feasibility of this method, a cracked R-fluted shells model was constructed. Under the action of the bending moment, the corner crack propagation is simulated through the reserved corner crack, and two crack tips with different stress fields are generated during the simulation. The experimental result indicates that the proposed method is effective for cracked R-fluted shells. It is also shown that the method has universal applicability for solving complex stress intensity factors on three-dimensional components

Dynamic Obstacle Detection Based on Background Compensation in Robot’s Movement Space

In the safety area of industrial production, robots are required to have the ability of quickly detecting the dynamic obstacles which appear in the working space of robots when robots move along a predefined route. In order to solve the problem of dynamic obstacles detection more effectively, the paper proposes a quick detection method based on background compensation for dynamic obstacles in robot movement space, which makes extraction of feature points on dynamic obstacles in robot movement space, establishes the background model of optical flow velocity field between adjacent frames and makes background compensation for images with the use of block-matching algorithm in order to realize quick and accurate dynamic obstacles detection in dynamic environment. The experiment results show that the obstacles detection method can effectively eliminate the background movement caused by the movement of camera at the end of robot and can extract a more complete target object. Moreover, it also has good robustness

The Use of an Edible Mushroom-Derived Renewable Carbon Material as a Highly Stable Electrocatalyst towards Four-Electron Oxygen Reduction

The development of highly stable and efficient electrocatalysts for sluggish oxygen reduction reaction (ORR) is exceedingly significant for the commercialization of fuel cells but remains a challenge. We here synthesize a new nitrogen-doped biocarbon composite material (N-BC@CNP-900) as a nitrogen-containing carbon-based electrocatalyst for the ORR via facile all-solid-state multi-step pyrolysis of bioprotein-enriched enoki mushroom as a starting material, and inexpensive carbon nanoparticles as the inserting matrix and conducting agent at controlled temperatures. Results show that the N-BC@CNP-900 catalyst exhibits the best ORR electrocatalytic activity with an onset potential of 0.94 V (versus reversible hydrogen electrode, RHE) and high stability. Meanwhile, this catalyst significantly exhibits good selectivity of the four-electron reaction pathway in an alkaline electrolyte. It is notable that pyridinic- and graphtic-nitrogen groups that play a key role in the enhancement of the ORR activity may be the catalytically active structures for the ORR. We further propose that the pyridinic-nitrogen species can mainly stabilize the ORR activity and the graphitic-nitrogen species can largely enhance the ORR activity. Besides, the addition of carbon support also plays an important role in the pyrolysis process, promoting the ORR electrocatalytic activity