PCR-Based Analytical Methods for Quantification and Quality Control of Recombinant Adeno-Associated Viral Vector Preparations

Recombinant adeno-associated viral vectors (rAAV) represent a gene therapy tool of ever-increasing importance. Their utilization as a delivery vehicle for gene replacement, silencing and editing, among other purposes, demonstrate considerable versatility. Emerging vector utilization in various experimental, preclinical and clinical applications establishes the necessity of producing and characterizing a wide variety of rAAV preparations. Critically important characteristics concerning quality control are rAAV titer quantification and the detection of impurities. Differences in rAAV constructs necessitate the development of highly standardized quantification assays to make direct comparisons of different preparations in terms of assembly or purification efficiency, as well as experimental or therapeutic dosages. The development of universal methods for impurities quantification is rather complicated, since variable production platforms are utilized for rAAV assembly. However, general agreements also should be achieved to address this issue. The majority of methods for rAAV quantification and quality control are based on PCR techniques. Despite the progress made, increasing evidence concerning high variability in titration assays indicates poor standardization of the methods undertaken to date. This review summarizes successes in the field of rAAV quality control and emphasizes ongoing challenges in PCR applications for rAAV characterization. General considerations regarding possible solutions are also provided.

Optimal management of efficiency gains manufacturing enterprises

Сформулированы две ключевые задачи, связанные с повышением эффективности производственных предприятий на основе оптимального управления качеством и снижением себестоимости производимой продукции. Решение первой задачи сводится к допустимому росту качества производимой предприятием продукции путем ее модернизации с учетом покупательской способности основной массы потребителей на различных сегментах рынка. Приведен критерий позволяющий определить оптимальные объемы производства продукции с различным уровнем качества для различных сегментов рынка, обеспечивающие производственному предприятию получение максимально возможной прибыли за счет роста потребительских свойств производимой продукции и повышения на этой основе ее рыночной стоимости. Решение второй задачи связано с условной минимизацией переменных издержек производства без потери требуемого уровня качества различных видов производимой предприятием продукции, которая обеспечивается путем сбалансированного ввода факторов производства в производственный процесс. Такой ввод факторов производства сопровождается снижением себестоимости производимой предприятием продукции и получением на этой основе дополнительной прибыли. Для проведения условной оптимизации, когда решение задачи оптимального управления получением дополнительной прибыли находится на границе области допустимых значений вводимых в него факторов, приводится критерий определяющий условие сбалансированного их ввода в производственный процесс и снижения на этой основе переменных издержек производства различных видов продукции в краткосрочном периоде. Two key tasks have been formulated related to improving the efficiency of manufacturing enterprises based on optimal quality management and reducing the cost of production. The solution to the first problem is reduced to an acceptable increase in the quality of the products produced by the enterprise by means of its modernization, taking into account the purchasing power of the bulk of consumers in various market segments. A criterion is given that allows you to determine the optimal production volumes of products with different levels of quality for different market segments, providing a manufacturing enterprise to obtain the maximum possible profit due to the growth of consumer properties of the products produced and on this basis increase its market value. The solution of the second problem is associated with the conditional minimization of variable production costs without losing the required level of quality of various types of products produced by the enterprise, which is ensured by balanced input of production factors into the production process. This input of factors of production is accompanied by a decrease in the cost of products manufactured by the enterprise and the receipt of additional profit on this basis. To carry out conditional optimization, when the solution to the problem of optimal control for obtaining additional profit is on the border of the region of admissible values ​​of the factors introduced into it, a criterion is given that determines the condition for their balanced input into the production process and, on this basis, reduce the variable production costs of various types of products in the short term.

Production Inventory Model under Time Dependent Demand, Uneven Manufacturing Rate and Manufacture Time Dependent Selling Price

In this paper, an inventory model for production of a single article with an uneven manufacturing rate and manufacturing time subsidiary selling cost has been considered. The considered production inventory model is accepted to create perfect items in beginning however because of different elements, after some time the production begins diminishing exponentially with time, i.e., the variable production rate has been thought of. The demand is time subordinate. Initially up to certain time, production rate remains constant. But after some time, due to various factors, production will decrease. Therefore, the efficiency (E) of such factors must be increased to get more production which can maintain the production efficiency cost which has been applied. Considering this fact inverse efficiency λ has been introduced in production rate. By utilizing differential calculus, expected maximum profit has been resolved. The goal of the examination is to decide the ideal arrangement for a production framework that expands the total benefit subject to certain limitations viable. Results are examined by means of a mathematical example to outline the hypothesis.

Robust scheduling and dispatching rules for high-mix collaborative manufacturing systems

Motivated by the increasing demand of mass customisation in production systems, this paper proposes a robust and adaptive scheduling and dispatching method for high-mix human-robot collaborative manufacturing facilities. Scheduling and dispatching rules are derived to optimally track the desired production within the mix, while handling uncertainty in job processing times. The sequencing policy is dynamically adjusted by online forecasting the throughput of the facility as a function of the scheduling and dispatching rules. Numerical verification experiments confirm the possibility to accurately track highly variable production requests, despite the uncertainty of the system.

Study of the Influence of Education and Literation of Entrepreneurship in Vocational High Schools: Indonesian Case

This paper aims to explain the factors that influence of entrepreneurship education and entrepeneurship literacy of vocational students (SMK). A paper based on research on 1,440 vocational grade XI students in 12 provinces in Indonesia obtained through random techniques, in the sense that each student has the same opportunity. Primary data collection is done through the distribution of questionnaires to students and analyzed by SEM techniques through the help of the Lisrel program version 8.70. The study found that the variables of school management, the role of teachers, teaching factories, and community participation had a positive influence on supporting facilities variables and entrepreneurship education variables. Facility support itself has a positive effect on entrepreneurship education, furthermore it has a positive effect on students' entrepreneurial literacy. On the other hand, external cooperation indicators contribute the strongest value for the school management variable, competent educator indicators of the teacher role variable, production training in the factory teaching variable, production marketing assistance in the community participation variable, and capital assistance information in the supporting facilities variable. In the entrepreneurship education variable, the indicator that contributes the strongest value is the identification of business prospects, while the entrepeneurship literacy variable is an indicator of business creativity. The implication is that entrepreneurship education efforts need to pay more attention to the above influence variables as well as indicators that have the effect strength of each variable. Received: 20 August 2020 / Accepted: 2 November 2020/ Published: 17 January 2021