Approaches to Enhance Precise CRISPR/Cas9-Mediated Genome Editing

Modification of the human genome has immense potential for preventing or treating disease. Modern genome editing techniques based on CRISPR/Cas9 show great promise for altering disease-relevant genes. The efficacy of precision editing at CRISPR/Cas9-induced double-strand breaks is dependent on the relative activities of nuclear DNA repair pathways, including the homology-directed repair and error-prone non-homologous end-joining pathways. The competition between multiple DNA repair pathways generates mosaic and/or therapeutically undesirable editing outcomes. Importantly, genetic models have validated key DNA repair pathways as druggable targets for increasing editing efficacy. In this review, we highlight approaches that can be used to achieve the desired genome modification, including the latest progress using small molecule modulators and engineered CRISPR/Cas proteins to enhance precision editing.     

Load transportation by dual arm robot using sliding mode control

In this study, a sliding mode controlled dual arm robotic system was designed. Such multi-arm, collaborative and synchronous robots typically are employed in hazardous situations such as radioactive materials transport explosives disposal and industrial applications. In the present study, a high performance, robust, non-chattering sliding mode controller (SMC) was developed for the purpose of safe load handling, transportation and trajectory realization. First, dynamic equations of robot/load interaction were derived. Then, the robust SMC was designed for the dual arm robotic system. In order to test the robustness of the proposed SMC, parameter variations and external disturbances were introduced to the system. Furthermore, for comparative purposes, the conventional and widely used, PID controller was also applied to the dual arm robot. Significantly, it was found that the SMC made smaller trajectory tracking errors than the PID controller. An overall analysis of the numerical results confirmed that the dual-arm robotic systems with the proposed SMC can safely and effectively be used in hazardous applications.     

Application of several non-linear prediction tools for estimating uniaxial compressive strength of granitic rocks and comparison of their performances

Uniaxial compressive strength (UCS) of rock is crucial for any type of projects constructed in/on rock mass. The test that is conducted to measure the UCS of rock is expensive, time consuming and having sample restriction. For this reason, the UCS of rock may be estimated using simple rock tests such as point load index (I _s(50)), Schmidt hammer (R _n) and p-wave velocity (V _p) tests. To estimate the UCS of granitic rock as a function of relevant rock properties like R _n, p-wave and I _s(50), the rock cores were collected from the face of the Pahang–Selangor fresh water tunnel in Malaysia. Afterwards, 124 samples are prepared and tested in accordance with relevant standards and the dataset is obtained. Further an established dataset is used for estimating the UCS of rock via three-nonlinear prediction tools, namely non-linear multiple regression (NLMR), artificial neural network (ANN) and adaptive neuro-fuzzy inference system (ANFIS). After conducting the mentioned models, considering several performance indices including coefficient of determination (R ²), variance account for and root mean squared error and also using simple ranking procedure, the models were examined and the best prediction model was selected. It is concluded that the R ² equal to 0.951 for testing dataset suggests the superiority of the ANFIS model, while these values are 0.651 and 0.886 for NLMR and ANN techniques, respectively. The results pointed out that the ANFIS model can be used for predicting UCS of rocks with higher capacity in comparison with others. However, the developed model may be useful at a preliminary stage of design; it should be used with caution and only for the specified rock types.     

Brief note on the influence of shape and percentage of gravel on the shear strength of sand and gravel mixtures

The paper records the influence of the shape and the percentage of gravel on the shear strength/frictional angle of sand and gravel mixtures using direct shear tests. The shear strength is mainly derived from the frictional forces developed due to sliding and interlock; they depend on the maximum particle size and shape, the uniformity coefficient, density and the effective normal stress. As the size of material in a mixture is variable, the shear strength also depends upon the ratio of the specimen diameter to the maximum particle size. In this study, two different shapes of limestone were used, angular and rounded, and the maximum gravel size was 6.3 mm in diameter. Air-dried samples were used in the tests. It is concluded that the shape and percentage of gravel have an important influence on the shear strength properties. Electronic Publication     

Correlation between slake durability and rock properties for some carbonate rocks

The paper reports a study to assess the relationship between slake durability indices and uniaxial compressive strength, Schmidt hardness, P-wave velocity, modulus of elasticity, effective porosity, water absorption and dry and saturated unit weight for seven types of carbonate rocks obtained from south west Turkey. It was found that the dry unit weight, saturated unit weight and Schmidt hardness gave the best relationship with first cycle slake durability (r = 0.99) while uniaxial compressive strength has a strong relationship with fourth cycle slake durability (r = 0.94). The results showed little difference in the correlation coefficients obtained after the fourth cycle. It is concluded that, for the rocks studied, the first and fourth cycles provide sufficiently good data on the durability for preliminary engineering/design works and that the second to fourth cycle results could be estimated using the first cycle slake durability index (r = 0.99–0.97).     

Different control applications on a vehicle using fuzzy logic control

In this paper, the active suspension control of a vehicle model that has five degrees of freedom with a passenger seat using a fuzzy logic controller is studied. Three cases are taken into account as different control applications. In the first case, the vehicle model having passive suspensions with an active passenger seat is controlled. In the second case, active suspensions with passive passenger seat combination are controlled. In the third case, both the passenger seat and suspensions have active controllers. Vibrations of the passenger seat in the three cases due to road bump input are simulated. At the end of the study, the results are compared in order to select the combination that supplies the best ride comfort.     

Effect of high pressure treatment on the quality of rainbow trout (Oncorhynchus mykiss) and mahi mahi (Coryphaena hippurus)

ABSTRACT:  High pressure processing (HPP) is becoming a promising seafood preservation method. The objective was to investigate the effect of HPP on quality of rainbow trout and mahi mahi during cold storage. Skinless fillets treated with different pressures (150, 300, 450, and 600 MPa for 15 min) and stored at 4 °C were analyzed at 1, 3, and 6 d storage. Red muscle was analyzed for lipid oxidation products by measuring thiobarbituric reactive substances (TBARS) and whole muscle was analyzed for total aerobic count, texture profile analysis, and color. A pressure of 300 MPa effectively inactivated the initial microbial population in rainbow trout (6-log reduction). However, inactivation of the initial population on mahi mahi was only about 4-log reduction at the same pressure. Microbial growth was significantly retarded after HPP. Color results showed that redness ( a * value) of rainbow trout at 300 MPa and above was significantly ( P < 0.05) lower compared to mahi mahi. TBARS values for rainbow trout increased with increased pressure, whereas the same trend was not seen for mahi mahi where maximum oxidation was found at 300 MPa and then declined. This study demonstrates the usefulness of HPP in seafood processing and the influence of species variation on processing parameters. The optimum HPP conditions for influencing lipid oxidation, microbial load, and color changes were found to be 300 MPa for rainbow trout and 450 MPa for mahi mahi.     

Utilizing rock mass properties for predicting TBM performance in hard rock condition

The key parameters on the estimation of tunnel-boring machine (TBM) performance are rock strength, toughness, discontinuity in rock mass, type of TBM and its specifications. The aim of this study is to both assess the influence of rock mass properties on TBM performance and construct a new empirical equation for estimation of the TBM performance. To achieve this aim, the database composed of actual measured TBM penetration rate and rock properties (i.e., uniaxial compressive strength, Brazilian tensile strength, rock brittleness/toughness, distance between planes of weakness, and orientation of discontinuities in rock mass) were established using the data collected from one hard rock TBM tunnel (the Queens Water Tunnel # 3, Stage 2) about 7.5 km long, New York City, USA. Intact rock properties were obtained from laboratory studies conducted at the Earth Mechanics Institute (EMI) in the Colorado School of Mines, CO, USA. Based on generated database, the statistical analyses were performed between available rock properties and measured TBM data in the field. The result revealed that rock mass properties have strong affect on TBM performance. It is concluded that TBM performance could be estimated as a function of rock properties utilizing new equation (r = 0.82).     

State-space aerodynamic model reveals high force control authority and predictability in flapping flight

Flying animals resort to fast, large-degree-of-freedom motion of flapping wings, a key feature that distinguishes them from rotary or fixed-winged robotic fliers with limited motion of aerodynamic surfaces. However, flapping-wing aerodynamics are characterized by highly unsteady and three-dimensional flows difficult to model or control, and accurate aerodynamic force predictions often rely on expensive computational or experimental methods. Here, we developed a computationally efficient and data-driven state-space model to dynamically map wing kinematics to aerodynamic forces/moments. This model was trained and tested with a total of 548 different flapping-wing motions and surpassed the accuracy and generality of the existing quasi-steady models. This model used 12 states to capture the unsteady and nonlinear fluid effects pertinent to force generation without explicit information of fluid flows. We also provided a comprehensive assessment of the control authority of key wing kinematic variables and found that instantaneous aerodynamic forces/moments were largely predictable by the wing motion history within a half-stroke cycle. Furthermore, the angle of attack, normal acceleration and pitching motion had the strongest effects on the aerodynamic force/moment generation. Our results show that flapping flight inherently offers high force control authority and predictability, which can be key to developing agile and stable aerial fliers.