scholarly journals Computational and experimental performance of CRISPR homing gene drive strategies with multiplexed gRNAs

2020 ◽  
Vol 6 (10) ◽  
pp. eaaz0525 ◽  
Author(s):  
Samuel E. Champer ◽  
Suh Yeon Oh ◽  
Chen Liu ◽  
Zhaoxin Wen ◽  
Andrew G. Clark ◽  
...  

The rapid evolution of resistance alleles poses a major obstacle for genetic manipulation of populations with CRISPR homing gene drives. One proposed solution is using multiple guide RNAs (gRNAs), allowing a drive to function even if some resistant target sites are present. Here, we develop a model of homing mechanisms parameterized by experimental studies. Our model incorporates several factors affecting drives with multiple gRNAs, including timing of cleavage, reduction in homology-directed repair efficiency due to imperfect homology, Cas9 activity saturation, gRNA activity level variance, and incomplete homology-directed repair. We find that homing drives have an optimal number of gRNAs, usually between two and eight, depending on the specific drive type and performance parameters. These results contradict the notion that resistance rates can be reduced to arbitrarily low levels by gRNA multiplexing and highlight the need for combined approaches to counter resistance evolution in CRISPR homing drives.

2019 ◽  
Author(s):  
Samuel E. Champer ◽  
Suh Yeon Oh ◽  
Chen Liu ◽  
Zhaoxin Wen ◽  
Andrew G. Clark ◽  
...  

ABSTRACTCRISPR homing gene drives potentially have the capacity for large-scale population modification or suppression. However, resistance alleles formed by the drives can prevent them from successfully spreading. Such alleles have been found to form at high rates in most studies, including those in both insects and mammals. One possible solution to this issue is the use of multiple guide RNAs (gRNAs), thus allowing cleavage by the drive even if resistance sequences are present at some of the gRNA target sequences. Here, we develop a high-fidelity model incorporating several factors affecting the performance of drives with multiple gRNAs, including timing of cleavage, reduction in homology-directed repair efficiency due to imperfect homology around the cleavage site, Cas9 activity saturation, variance in the activity level of individual gRNAs, and formation of resistance alleles due to incomplete homology-directed repair. We parameterize the model using data from homing drive experiments designed to investigate these factors and then use it to analyze several types of homing gene drives. We find that each type of drive has an optimal number of gRNAs, usually between two and eight, dependent on drive type and performance parameters. Our model indicates that utilization of multiple gRNAs is insufficient for construction of successful gene drives, but that it provides a critical boost to drive efficiency when combined with other strategies for population modification or suppression.


2020 ◽  
Vol 99 (4) ◽  
pp. 405-411
Author(s):  
Elena Ju. Gorbatkova

Introduction. The important factors affecting health and performance of young people are the conditions of education, in particular, a comfortable microclimate in the classrooms of higher educational institutions. Materials and methods. In view of the urgency of this problem, an analysis was made of the microclimate parameters of educational organizations of different profiles (Ufa city, the Republic of Bashkortostan). 294 classrooms were studied in 22 buildings of 4 leading universities in Ufa. A total of 3,822 measurements were taken to determine the parameters of the microclimate. The analysis of ionizing radiation in the aerial environment of classrooms. There was performed determination of radon and its affiliated products content. In order to assess the conditions and lifestyle of students of 4 higher educational institutions of the city of Ufa, we conducted an anonymous survey of 1,820 students of I and IV years of education. Results. The average temperature in the classrooms of all universities studied was 23.9±0.09 C. The average relative humidity in all classrooms was 34.2 ± 0.42%. Analysis of ionizing radiation (radon and its daughter products decay) in the aerial environment of the classrooms and sports halls located in the basement determined that the average annual equivalent equilibrium volumetric activity of the radon daughter products (EROA ± Δ222Rn) ranged from 28 ± 14 to 69 ± 34.5 meter, which meets the requirements established by SanPiN. Conclusion. The hygienic assessment of the microclimate parameters of educational institutions of various profile revealed a number of deviations from the regulated norms. The results indicate the need to control the parameters of the microclimate, both from the administration of universities, and from the professors. According to the results of the study, recommendations were prepared for the management of higher educational institutions in Ufa.


Author(s):  
Petar Kazakov ◽  
Atanas Iliev ◽  
Emil Marinov

Over the decades, more attention has been paid to emissions from the means of transport and the use of different fuels and combustion fuels for the operation of internal combustion engines than on fuel consumption. This, in turn, enables research into products that are said to reduce fuel consumption. The report summarizes four studies of fuel-related innovation products. The studies covered by this report are conducted with diesel fuel and usually contain diesel fuel and three additives for it. Manufacturers of additives are based on already existing studies showing a 10-30% reduction in fuel consumption. Comparative experimental studies related to the use of commercially available diesel fuel with and without the use of additives have been performed in laboratory conditions. The studies were carried out on a stationary diesel engine СМД-17КН equipped with brake КИ1368В. Repeated results were recorded, but they did not confirm the significant positive effect of additives on specific fuel consumption. In some cases, the factors affecting errors in this type of research on the effectiveness of fuel additives for commercial purposes are considered. The reasons for the positive effects of such use of additives in certain engine operating modes are also clarified.


Author(s):  
E.O. Chernova

The article gives an analysis of the results of authorial experimental studies. Motivational factors affecting adolescents' participation in criminal groups are considered, they are: dominant groups of motives, the predominance of aspiration to success or avoidance of failures. Thus, the author explores the subjective potential of the personality of adolescent groupers. According to the results of the research, the author concludes that the specificity of the motivation of such adolescents consists in the predominance of material motives, social motives (involvement in social communities, groupings) and motives of recognition and respect. The author notes that the motivation for avoiding failures is more characteristic of such adolescents than the motivation for the pursuit of success. It is concluded that the data obtained can serve as a basis for developing preventive measures when working with adolescents at risk.


Author(s):  
E. M. Ratnikov ◽  
D. O. Milko

Annotation Purpose. Development of a program and methods for conducting experimental studies of the extrusion process with the definition of parameters and modes of operation of the extruder to improve its energy performance. Methods. Methods of mathematical statistics, synthesis, analysis, description and modeling were used. Results. The application of mathematical methods, in particular mathematical planning, reduces the number of experiments several times, and allows to evaluate the role of influencing factors, obtain a mathematical model of the process and determine the optimal conditions for its parameters and modes, etc. Conclusions. The methodology for experimental studies of a screw extruder is presented with the necessary equipment and methodology for processing the obtained experimental data. A mathematical method of planning, which reduces the number of experiments several times, allows us to evaluate the role of factors affecting productivity and energy intensity is presented. Keywords: extruder, auger, nutrients, research methodology, extrusion, processing, feed.


Author(s):  
T. N. Antipova ◽  
D. S. Shiroyan

The system of indicators of quality of carbon-carbon composite material and technological operations of its production is proved in the work. As a result of the experimental studies, with respect to the existing laboratory equipment, the optimal number of cycles of saturation of the reinforcing frame with a carbon matrix is determined. It was found that to obtain a carbon-carbon composite material with a low cost and the required quality indicators, it is necessary to introduce additional parameters of the pitch melt at the impregnation stage.


Author(s):  
Michael Mutz ◽  
Anne K. Reimers ◽  
Yolanda Demetriou

Abstract Observational and experimental studies show that leisure time sporting activity (LTSA) is associated with higher well-being. However, scholars often seem to assume that 1) LTSA fosters “general” life satisfaction, thereby ignoring effects on domain satisfaction; 2) the effect of LTSA on well-being is linear and independent of a person’s general activity level; 3) the amount of LTSA is more important than the repertoire of LTSA, i.e. the number of different activities; 4) all kinds of LTSA are equal in their effects, irrespective of spatial and organisational context conditions. Using data from the German SALLSA-Study (“Sport, Active Lifestyle and Life Satisfaction”), a large-scale CAWI-Survey (N = 1008) representing the population ≥ 14 years, the paper takes a closer look on these assumptions. Findings demonstrate that LTSA is associated with general life satisfaction and domain-specific satisfaction (concerning relationships, appearance, leisure, work and health), but that the relationship is most pronounced for leisure satisfaction. Associations of sport with life satisfaction, leisure satisfaction and subjective health are non-linear, approaching an injection point from which on additional LTSA is no longer beneficial. Moreover, findings lend support to the notion that diversity in LTSA matters, as individuals with higher variation in sports activities are more satisfied. Finally, results with regard to spatial and organizational context suggest that outdoor sports and club-organized sports have additional benefits.


2020 ◽  
pp. 097674792096686
Author(s):  
Yudhvir Singh ◽  
Ram Milan

Public sector banks have been merged by the government in the last few years. This is the rationale behind conducting this study. The purpose of this article is to determine the factors affecting the performance of public sector banks in India and the interrelationship between bank-specific determinants and performance of public sector banks. In this article, we shall analyse the financial data of all the public sector commercial banks for a period spread across 11 years (2009–2019); Capital adequacy, Assets quality, Management efficiency, Earning, and Liquidity (CAMEL) has been used as a performance determinant; system generalised method of moments (GMM) analysis has been used to find the effect of determinants on the performance measurement of public sector banks; and CCA (canonical correlation analysis) has been used to find the interrelationship between the bank-specific determinants and the performance of public sector banks. The finding has important implications in terms of performance in the banking sector. Certain limitations of this study are: It is based on secondary data. The study only covers the financial aspects and not the non-financial aspects. It is found that the asset quality is negatively related with performance of public sector banks. Liquidity and inflation are inversely related to performance of public sector banks in India. Capital adequacy is positively related with banks’ performance, but inversely related with banks’ interest margin. GDP growth has a significant positive impact on banks’ performance, but inversely related with banks’ interest income. Inflation rate is inversely related with banks’ performance. Banking sector reforms are insignificantly related with banks’ performance.


2021 ◽  
Vol 22 (2) ◽  
pp. 348-363
Author(s):  
Damian Boniface Sambuo ◽  
Stephen Kirama ◽  
Kitala Malamsha

Determination of fish landing price is important, as the same contributes to the structure, conduct and performance of the fish market in Lake Victoria. Determination of relevant landing price is a gap to console between fishermen, agents (middlemen), processors and the government. The main objective of this study was therefore to examine fish price determination. Specifically, to examine the methods for fish price determination and analyse factors that affect fish landing price in Lake Victoria, a cross-sectional design was employed, and 300 respondents were randomly selected from two district councils, namely, Sengerema and Buchosa. Both qualitative and quantitative data were analysed using descriptive statistics and inferential analysis. Findings show that landing price is determined through formal negotiation with processors, consultation with other traders, informal negotiation with buyers and Beach Management Unit (BMU). The study concluded that these are the common methods used to determine landing prices. Also, distance from fishing to onshore landing centres, market information channels, age and experiences of the fishermen are the factors significantly found affecting landing price. It is recommended that the mechanism for setting up fishery price, fish market structure, fishery information and the formation of fishery regulatory body needs fishery policy and sector reforms that mark the determination of fish landing price.


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