While CRISPR-Cas systems hold tremendous potential for engineering the human genome, it is unclear how well each system performs against one another in both non-homologous end joining (NHEJ)-mediated ...and homology-directed repair (HDR)-mediated genome editing.
We systematically compare five different CRISPR-Cas systems in human cells by targeting 90 sites in genes with varying expression levels. For a fair comparison, we select sites that are either perfectly matched or have overlapping seed regions for Cas9 and Cpf1. Besides observing a trade-off between cleavage efficiency and target specificity for these natural endonucleases, we find that the editing activities of the smaller Cas9 enzymes from Staphylococcus aureus (SaCas9) and Neisseria meningitidis (NmCas9) are less affected by gene expression than the other larger Cas proteins. Notably, the Cpf1 nucleases from Acidaminococcus sp. BV3L6 and Lachnospiraceae bacterium ND2006 (AsCpf1 and LbCpf1, respectively) are able to perform precise gene targeting efficiently across multiple genomic loci using single-stranded oligodeoxynucleotide (ssODN) donor templates with homology arms as short as 17 nucleotides. Strikingly, the two Cpf1 nucleases exhibit a preference for ssODNs of the non-target strand sequence, while the popular Cas9 enzyme from Streptococcus pyogenes (SpCas9) exhibits a preference for ssODNs of the target strand sequence instead. Additionally, we find that the HDR efficiencies of Cpf1 and SpCas9 can be further improved by using asymmetric donors with longer arms 5' of the desired DNA changes.
Our work delineates design parameters for each CRISPR-Cas system and will serve as a useful reference for future genome engineering studies.
This paper is concerned with the numerical solution of the nonlinear Schrödinger (NLS) equation with Neumann boundary conditions by quintic B-spline Galerkin finite element method as the shape and ...weight functions over the finite domain. The Galerkin B-spline method is more efficient and simpler than the general Galerkin finite element method. For the Galerkin B-spline method, the Crank Nicolson and finite difference schemes are applied for nodal parameters and for time integration. Two numerical problems are discussed to demonstrate the accuracy and feasibility of the proposed method. The error norms L 2 , L ∞ and conservation laws I 1 , I 2 are calculated to check the accuracy and feasibility of the method. The results of the scheme are compared with previously obtained approximate solutions and are found to be in good agreement.
The non-linear Schrödinger (NLS) equation has often been used as a model equation in the study of quantum states of physical systems. Numerical solution of NLS equation is obtained using cubic ...B-spline Galerkin method. We have applied the Crank–Nicolson scheme for time discretization and the cubic B-spline basis function for space discretization. Three numerical problems, including single soliton, interaction of two solitons and birth of standing soliton, are demonstrated to evaluate to the performance and accuracy of the method. The error norms and conservation laws are determined and found to be in good agreement with the published results. The obtained results show that the approach is feasible and accurate. The proposed method has almost second order convergence. The linear stability of the method is performed using the Von Neumann method.
The purpose of this study is to find the most effective strategies for eliminating shyness amongst engineering students through co-curricular activities. As shyness causes negative impacts towards ...students' development, it becomes a major concern for lecturers and student affairs departments to find strategies that can solve the problem. However, shyness cannot be eliminated solely through the formal classroom learning. Ironically, co-curricular activities provide a good platform to develop students' potentials, but previous research failed to analyse the specific co-curricular activities that can decrease the impacts of shyness. This paper seeks to address this gap. 102 articles were reviewed and 6 articles were used to suggest co-curricular activities that can reduce the impact of shyness. Finding shows that co-curricular activities such as debate, choir, sports team, physical activities and exercise, career and technical student organizations and entrepreneurship clubs and societies are found to be the core activities that can enhance the social and communication skill, participation in the teaching and learning, self-esteem and career development of shy students. The recommendation activities can be used by the student affairs departments to eliminate shyness amongst engineering students by ensuring their active participation in the respective clubs.
Shy children tend to have verbal communication problems and low self-esteem. However, the confidence and communication skills of these children could not be developed solely through classroom ...instructions. Ironically, the co-curricular program provides a good medium for communication activities that can improve their confidence and communication skills. Therefore, this study examined children's communication skills and communication activities during the co-curricular program at their school. The areas of study were the children's level of shyness, the implementation and the effectiveness of communication activities in the co-curricular program. The quantitative study adopted a non-experimental descriptive research design. The respondents were 357 Grade Six students from elementary schools in Segamat, Johor which was selected from a random sampling. Results showed that most children were having a medium level of shyness and the communication activities were moderately implemented in the co-curricular program at their schools. Almost all respondents viewed communication activities in the co-curricular program as very effective to reduce shyness, enhance their self-esteem and communication skills. Hence, communication skills of shy children can be enhanced through appropriate communication activities conducted during the co-curricular program. Children should be encouraged and trained to speak in public by participating in the debate, public speaking and theatre activities during the co-curricular to reduce their shyness.
A method based on extended cubic B-spline is proposed to solve a linear system of second-order boundary value problems. In this method, two free parameters,
λ
1
and
λ
2
, play an important role in ...producing accurate results. Optimization of these parameters are carried out and the truncation error is calculated. This method is tested on three examples. The examples suggest that this method produces comparable or more accurate results than cubic B-spline and some other methods.
Dye sensitized solar cells (DSSC) is one of the promising candidates which are efficient, low-cost, and clean hybrid molecular solar cell devices. Zinc oxide (ZnO) has been widely used as the ...phoanode in DSSC due to its excellent charge conduction mechanism, yet still suffers from poor cell efficiency. In this study, aluminium doped ZnO (ZnO:Al) and Ni doped ZnO (ZnO:Ni) were studied as photoanode material in DSSC using solar cell capacitance simulator (SCAPS) simulation, and the electrolyte liquid considered a single solid p-type layer as hole transporting materials. Both studied photoanodes have demonstrated better cell performance than pure ZnO photoanode due to the small amount of aluminium (Al) and nikel (Ni) impurities added have enhanced the physiochemical properties of ZnO films. A power conversion efficiency (PCE) of 3.96% was obtained at 3 mol% ZnO:Al photoanode with optimized key parameters. These simulation results proved an opportunity to improve the performance of the DSSCs via doping engineering into the ZnO photonaode.
Perovskite solar cells have shown remarkable performance and improvements in terms of solar cell efficiency. The ETL material is one of the important components in perovskite solar cells in ...conducting electrons to produce current. Here, ZnO was used as ETL material in a perovskite solar cell using the SCAPS 1D simulation software. The ZnO ETL showed poor cell efficiency due to its reaction with the perovskite material. A small amount of Al doped into ZnO was introduced to enhance the physiochemical properties of the ZnO against perovskite materials. Al concentrations were varied between 1 and 4 mol% to observe the effect on cell efficiency. Compared with a conventional ZnO ETL solar cell with 0 mol% Al perovskite, the Al-doped based solar cell showed better performance. Meanwhile, perovskite solar cells with 1 mol% Al-doping and appropriate layer thickness showed the best cell performance in improving the charge transport mechanism, resulting in increased cell efficiency. Thus, the parameters studied can be a guide in the fabrication process.
Extracellular vesicles (EVs) are increasingly recognised as a pivotal player in cell-cell communication, an attribute of EVs that derives from their ability to transport bioactive cargoes between ...cells, resulting in complex intercellular signalling mediated by EVs, which occurs under both physiological and pathological conditions. In the context of cancer, recent studies have demonstrated the versatile and crucial roles of EVs in the tumour microenvironment (TME). Here, we revisit EV biology, and focus on EV-mediated interactions between cancer cells and stromal cells, including fibroblasts, immune cells, endothelial cells and neurons. In addition, we focus on recent reports indicating interactions between EVs and non-cell constituents within the TME, including the extracellular matrix. We also review and summarise the intricate cancer-associated network modulated by EVs, which promotes metabolic reprogramming, horizontal transfer of neoplastic traits, and therapeutic resistance in the TME. We aim to provide a comprehensive and updated landscape of EVs in the TME, focusing on oncogenesis, cancer progression and therapeutic resistance, together with our future perspectives on the field.
In this article, the Galerkin method, based on quintic B-spline function as the shape and weight functions is described for the numerical solution of the second order coupled nonlinear Schrödinger ...equations. Finite difference and Crank–Nicolson schemes are used to discretize the time derivative and nodal parameters respectively. Three numerical problems are presented to assess the accuracy and capability of the proposed method. The maximum errors, norms and conserved quantities are calculated. The obtained numerical results show that the present scheme with higher order B-spline as basis and weight functions performs well and accurately. The numerical results are compared with analytical and published results.
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