Early Stages Of Production Research Articles

An automated, low volume, and high-throughput analytical platform for aggregate quantitation from cell culture media

High throughput screening methods have driven a paradigm shift in biopharmaceutical development by reducing the costs of good manufactured (COGM) and accelerate the launch to market of novel drug products. Scale-down cell culture systems such as shaken 24- and 96-deep-well plates (DWPs) are used for initial screening of hundreds of recombinant mammalian clonal cell lines to quickly and efficiently select the best producing strains expressing product quality attributes that fit to industry platform. A common modification monitored from early-stage product development is protein aggregation due to its impact on safety and efficacy. This study aims to integrate high-throughput analysis of aggregation-prone therapeutic proteins with 96-deep well plate screening to rank clones based on the aggregation levels of the expressed proteins. Here we present an automated, small-scale analytical platform workflow combining the purification and subsequent aggregation analysis of protein biopharmaceuticals expressed in 96-DWP cell cultures. Product purification was achieved by small-scale solid-phase extraction using dual flow chromatography (DFC) automated on a robotic liquid handler for the parallel processing of up to 96 samples at a time. At-line coupling of size-exclusion chromatography (SEC) using a 2.1 mm ID column enabled the detection of aggregates with sub-2 µg sensitivity and a 3.5 min run time. The entire workflow was designed as an application to aggregation-prone mAbs and “mAb-like” next generation biopharmaceuticals, such as bispecific antibodies (BsAbs). Application of the high-throughput analytical workflow to a shake plate overgrow (SPOG) screen, enabled the screening of 384 different clonal cell lines in 32 h, requiring < 2 μg of protein per sample. Aggregation levels expressed by the clones varied between 9 and 76%. This high-throughput analytical workflow allowed for the early elimination of clonal cell lines with high aggregation, demonstrating the advantage of integrating analytical testing for critical quality attributes (CQAs) earlier in product development to drive better decision making.

Exploring the Essence of Continuous Experimentation

Context: Today's software industry is faced with rapidly changing requirements and high expectations from customers and users. Agile software development with a focus on rapid and frequent product deployment to end-users calls for equally continuous feedback acquisition, guiding software design and supporting evidencebased product development decisions. For keeping pace and succeeding on the highly competitive software market it is essential for companies to quickly and reliably evaluate their ideas based on real usage experiences in a natural context. This can be enabled using Continuous Experimentation (CE) - an approach to close the feedback cycle and tightly integrate the empirical evaluation of new features into the software development process. Objectives: With this project I aim at creating an understanding of CE as practiced and theorised today. Furthermore, my goal is to identify the smallest set of prerequisites for successfully implementing systematic experimentation practices into companies' software development process. I want to find solutions for companies to adopt CE as most suitable to their product stage, process maturity, and available resources; and enable organisations to systematically run experiments for data-driven decision-making. Methods: In addition to a currently on-going multivocal literature review, the project will involve empirical studies following a design science approach. Starting with a practitioner survey or interview, and a pilot case study for finding both, the typical hurdles encountered and the minimum requirements needed to apply CE in any company, the project will transition into an iterative multiple-case study, where proposed solutions are to be evaluated. Conclusions: The proposed doctoral research project will contribute to an increased understanding of systematic experimentation practices in different organisational settings, and strives for providing actionable solutions for enabling more flexible software development which can quickly react to feedback gained through experimentation, as well as an evaluation of these suggested solutions. Especially, this project aims at the creation of an easy-to-adopt approach called light-weight CE, which allows also companies with few resources or projects involving an earlystage product to benefit from the advantages of CE.

A Computational Approach to Identifying Engineering Design Problems

Abstract Identifying new problems and providing solutions are necessary tasks for design engineers at early-stage product design and development. A new problem fosters innovative and inventive solutions. Hence, it is expected that engineering design pedagogy and practice should equally focus on engineering design problem-exploring (EDPE)—a process of identifying or coming up with a new problem or need at the early-stage of design, and engineering design problem-solving (EDPS)—a process of developing engineering design solutions to a given problem. However, studies suggest that EDPE is scarcely practiced or given attention to in academia and industry, unlike EDPS. The aim of this paper is to investigate the EDPE process for any information relating to its scarce practice in academia and industry. This is to explore how emerging technologies could support the process. Natural models and phenomena that explain the EDPE process are investigated, including the “rational” and “garbage can” models, and associated challenges identified. A computational framework that mimics the natural EDPE process is presented. The framework is based on Markovian model and computational technologies, including machine learning. A case study is conducted with a sample size of 43 participants drawn worldwide from the engineering design community in academia and industry. The case study result shows that the first-of-its-kind computational EDPE framework presented in this paper supports both novice and experienced design engineers in EDPE.

Utilisation of locust bean (Parkia biglobosa) pulp as a natural egg quality enhancer in laying hens

Abstract This study was carried out to improve commercial egg production using parkia pulp which is usually washed off during the processing of parkia seed into spice. A total of 54 Hyline brown Agrited brand pullets were randomly allotted to 3 treatments, 6 birds per replicate. Parkia pulp was included in the birds’ drink (0%, 1%, and 2% parkia pulp) from 08:00 h to 10:00 h followed by clean cool water daily from day 147 to day 245 (early egg production phase). At day 420 to 448 (late egg production phase) conventional multivitamins, 1% and 2% parkia pulp were included in drinking water for 3 days in a week 08:00 h to 17:00 h. Data on the growth of birds, egg production, and egg internal and external quality were measured and analysed using ANOVA at p &lt; 0.05. The weight of birds in the early egg production phase was directly proportional to the quantity of parkia pulp included in the parkia pulp drink. The number of eggs produced per bird (64.85) was significantly higher from the birds on 1% parkia pulp drink, whereas from the egg quality indicators, egg weight (65.03 g), length (56.15 mm), shell weight (8.06 g), and albumen weight (41.75 g) were all significantly higher at 2% inclusion level of parkia pulp drink in the early stage of egg production. In the late phase there was no significant difference among the treatments in the internal and external egg qualities but the weight of birds on parkia drink was high at p ≤ 0.05. The results of our study show that parkia pulp inclusion in commercial laying hen drink enhances the quality and quantity of egg production.

Bottom-hole pressure drawdown management of fractured horizontal wells in shale gas reservoirs using a semi-analytical model

Due to strong stress sensitivity resulted from unconventional tight formationsit is of practical interest to formulate a reasonable pressure drawdown plan to improve gas extraction recovery. The impact of water-shale interactions on the reservoir permeability was previously ignored in the managed pressure drawdown optimization. The controlled-pressure production dynamic analysis was mostly conducted using numerical simulation, lack of rigorous theoretical support. Hence in this paper, a theoretical production prediction model was proposed and verified with HIS RTA 2015by incorporating multiple pressure drawdown mechanisms and various non-linear gas flow process. The on-site production effects dominated by two different pressure drop methods was further compared, indicating that compared to depressurization production, the production reversion can occur in the controlled pressure production process and the EUR of single well can be increased by about 30% under the control of managed pressure drawdown approach. Finally, the pressure drawdown optimization strategy was carried out on the field test from the both production effect and economic benefits, which demonstrated that the best economic solution can generally be obtained in the early stage of production. The research results can be closely linked to the on-site production practice of shale gas wells, providing insights into designing optimized production strategy scheme.

Impact of maize particle size on egg production and egg quality of White Leghorns in early stage of production

The aim of the present study was to determine the effect of the maize particle size on the performance of layers. Five maize-soybean based diets were formulated with maize particle size of 4.0, 6.0, 8.0, 10.0 and 12.0 mm sieve size with five treatments (T1: 4.0 mm mash diet; T2: 6.0 mm mash diet; T3: 8.0 mm mash diet; T4: 10.0 mm mash diet; T5: 12.0 mm mash diet) fed from 20 to 28 weeks of age. Each treatment was replicated three times, with 10 birds in each replicate. The results showed no significant difference in average daily feed intake, live weight, hen day egg production percentage, egg mass and egg indices except for haugh unit, which was highest for the 4 mm screen size and lowest for the 12 mm screen size in layers from 20 to 28 weeks of age. FCR (g/g egg mass) was highest for T3 as compared to the average of other treatments not affected by either of the feeds. In conclusion, the size of the screen used to mill the grain had no impact on hen production within the range of the study. Furthermore, the decision to grind grains more coarsely than is already customary would be favourable for the environment and the economy because it would reduce the amount of energy, labour, and time utilised in feed mills.

Celts, Slabs, and Space: Organisation of lithic reduction strategies in Tamil Nadu, India

• Lithic reduction strategies for the manufacture of stone celts in SE India. • Dolerite ‘quarries’ for exploitation of slabs for celt façonnage and debitage sequences. • Spatial variability in organization of areas of quarrying, polishing/grinding and use/discard. • Association with early agro-pastoral communities. • Comparison with other celt production sites in India and significance for behaviour. Polished stone celts form a key cultural signifier of the Indian Neolithic/Chalcolithic, although continuing in time into later cultural phases. However, in India, celt manufacturing sequences are rarely studied despite their significance for investigating behavioural organisation, mobility and functionality amongst early agro-pastoral populations. Here we present new data from two celt-manufacturing complexes in Southern India, with a focus on the early stages of celt production at ‘quarry’ sites. We highlight diverse reduction sequences on slabs and flakes, with implications in terms of decision making in knapping strategies and spatial differentiation of activities across the landscape. We identify-three different reduction sequences focused on dolerite slabs and flakes, and granite/gneiss clasts. Spatial variability in reduction stages is observed in locations reflecting quarrying and early stages of knapping near dolerite dykes, grinding and polishing localities, and areas of final stocking/use and discard, distributed across the landscape. We also highlight the local reuse of celts by village populations in ritualistic contexts. We compare the reduction sequences noted at sites in the study region with similar sites in Southern India, thereby contributing to a wider perspective on celt-manufacturing technologies in India.

Plant Growth and Microbiota Structural Effects of Rhizobacteria Inoculation on Mahogany (Swietenia macrophylla King [Meliaceae]) under Nursery Conditions

Swietenia macrophylla is a tropical timber species of ecological and economic importance. However, its slow vegetative growth and root development in nurseries strongly limit its production. This study evaluated the effect of 10 rhizobacteria strains during the early stages of production of S. macrophylla. Superficially disinfected seeds were inoculated with rhizobacteria under commercial nursery conditions. Inoculation was complemented by initial fertilization without growth regulators, fungicides, or bactericides. The results indicate that the rhizobacteria strains induce different responses in plants. Significant differences in plant biomass and root architecture were found. Treatments inoculated with Bacillus sp., Bacillus polyfermenticus, and Bacillus siamensis strains; showed an increase of up to 41% (dry weight). Plants increased root biomass by 30% when inoculated with S. siamensis. All inoculated strains were identified as members of the genus Bacillus spp., and their presence three months after inoculation was assessed by 16S rRNA gene-based amplicon massive sequencing. We found that Bacillus sp. genus was only present in inoculated treatments, suggesting that inoculated bacteria could establish themselves successfully as part of the microbiota. These results support the advantages of using PGPRs in commercial tropical tree production.

Oil-gas two-phase seepage model in fractured carbonate reservoirs

Fractures are developed in fractured carbonate reservoirs. Traditional fracture characterization methods and seepage mathematical models cannot accurately describe the complex spatial distribution of large-scale fractures and their stress sensitivity, and do not consider the two-phase seepage of oil and gas, resulting in the dynamic analysis results have large errors. Aiming at this problem, a two-phase seepage model of oil and gas in fractured carbonate reservoirs considering stress sensitivity is established in this paper, and the semi-analytical solution of the model is obtained by using three-dimensional source function theory and finite difference method. The accuracy of the model is verified by comparison with commercial numerical simulation software, the production performance curve of oil and gas two-phase is drawn, and the influence of key seepage parameters of reservoirs and fractures on production performance is analyzed. The results show that the hybrid solution method of 3D source function and finite difference can realize the accurate and efficient solution of 3D discrete fracture oil and gas two-phase seepage model. The stress sensitivity effect leads to serious loss of fracture permeability and increase of fluid seepage resistance, which seriously affects the production of oil wells. The greater the fracture permeability, the higher the initial value of production, and the higher the position of the production curve. The longer fracture length, the higher the production curve in the early and middle production stages, and the slower the production decline.

How can age-based vaccine allocation strategies be optimized? A multi-objective optimization framework.

Human life is deeply influenced by infectious diseases. A vaccine, when available, is one of the most effective ways of controlling the spread of an epidemic. However, vaccine shortage and uncertain vaccine effectiveness in the early stage of vaccine production make vaccine allocation a critical issue. To tackle this issue, we propose a multi-objective framework to optimize the vaccine allocation strategy among different age groups during an epidemic under vaccine shortage in this study. Minimizing total disease onsets and total severe cases are the two objectives of this vaccine allocation optimization problem, and the multistage feature of vaccine allocation are considered in the framework. An improved Strength Pareto Evolutionary Algorithm (SPEA2) is used to solve the optimization problem. To evaluate the two objectives under different strategies, a deterministic age-stratified extended SEIR model is developed. In the proposed framework, different combinations of vaccine effectiveness and vaccine production capacity are investigated, and it is identified that for COVID-19 the optimal strategy is highly related to vaccine-related parameters. When the vaccine effectiveness is low, allocating most of vaccines to 0–19 age group or 65+ age group is a better choice under a low production capacity, while allocating most of vaccines to 20–49 age group or 50–64 age group is a better choice under a relatively high production capacity. When the vaccine effectiveness is high, a better strategy is to allocate vaccines to 65+ age group under a low production capacity, while to allocate vaccines to 20–49 age group under a relatively high production capacity.

Wearable Devices in Diving: Scoping Review.

BackgroundWearables and their benefits for the safety and well-being of users have been widely studied and have had an enormous impact on the general development of these kinds of devices. Yet, the extent of research into the use and impact of wearable devices in the underwater environment is comparatively low. In the past 15 years, there has been an increased interest in research into wearables that are used underwater, as the use of such wearables has steadily grown over time. However, there has so far been no clear indication in the literature about the direction in which efforts for the design and construction of underwater wearable devices are developing. Therefore, the analysis presented in this scoping review establishes a good and powerful basis for the further development and orientation of current underwater wearables within the field.ObjectiveIn this scoping review, we targeted wearable devices for underwater use to make a comprehensive map of their capabilities and features and discuss the general direction of the development of underwater wearables and the orientation of research into novel prototypes of these kinds of devices.MethodsIn September 2021, we conducted an extensive search for existing literature on 4 databases and for grey literature to identify developed prototypes and early-stage products that were described and tested in water, could be worn and interacted with (eg, displays, buttons, etc), and were fully functional without external equipment. The studies were written in English, came from peer-reviewed academic sources, and were published between 2005 and 2021. We reviewed each title and abstract. The data extraction process was carried out by one author and verified by another author.ResultsIn total, 36 relevant studies were included. Among these, 4 different categories were identified; 18 studies dealt primarily with safety devices, 9 dealt with underwater communication devices, 7 dealt with head-up displays, and 2 dealt with underwater human-computer interaction approaches. Although the safety devices seemed to have gained the most interest at the time of this study, a clear trend toward underwater communication wearables was identified.ConclusionsThis review sought to provide a first insight into the possibilities and challenges of the technologies that have been used in and for wearable devices that are meant for use in the underwater environment. Among these, underwater communication technologies have had the most significant influence on future developments. Moreover, a topic that has not received enough attention but should be further addressed is human-computer interaction. By developing underwater wearables that cover 2 or more of the technology categories that we identified, the extent of the benefits of such devices can be significantly increased in the future.

The Detection of Open and Leakage Faults for Prebond TSV Test Based on Weak Current Source

During the manufacturing process of three-dimensional integrated circuits (3-D ICs), many defects may occur in through-silicon vias (TSVs). These defects affect the integrity of the signal passing through TSVs, therefore detecting these defects in the early production stage is crucial. This article proposed a built-in-self-test (BIST) method with a simple test structure and easily implemented fault detection process. Due to the fact that the defects in TSVs influence the charge/discharge speed of TSVs’ equivalent capacitance, a weak current source is designed as the central part of the proposed test structure, which can measure the TSVs’ charge/discharge speed and quantify it using digital values. The effectiveness and robustness of the proposed method is validated by HSPICE simulation. The minimum measurable fault, test time, and test circuit area are also assessed in this article. The simulation results show that the method this article proposed can detect weaker faults, compared with the traditional test methods.

Towards harmonised and regionalised life cycle assessment of fruits: A review on citrus fruit

The citrus fruit sector is globally relevant. Considering the great contribution of agri-food systems to environmental impacts, assessing and reducing them can make a positive contribution to the environment. Life Cycle Assessment (LCA) is a widespread tool used to quantify the complex environmental interactions of agri-food systems in general and perennial fruit crops in particular. However, methodological aspects need to be harmonised to perform useful and representative LCAs on fruits. The goal of this study is to provide an updated descriptive and critical review of the state of the art of LCA research into citrus fruits. We aim to identify the main methodological decisions, paying special attention to crop cycle modelling and regional representability. Bearing this in mind, we propose recommendations for a harmonised application of LCA on citrus fruits, identifying areas worthy of further research. The main hotspots of the production process are also identified, to understand where improvement efforts should be directed to. To this end, a two-step search was carried out and a final sample of 23 records was obtained. The production of both pesticides and fertilisers together with their on-field emissions are the main hotspots in the reviewed articles. Regarding areas for further research, a lack of studies into the early stages of citrus fruit production is detected. Farm representativeness, both temporal and spatial, is highlighted as a critical issue when assessing regional fruit production. This implies improving life cycle inventories, namely by using site-specific methods to estimate fertiliser and pesticide emissions, developing regionalized datasets of agricultural inputs, and strengthening water inventories. As to the impact assessment, the estimation of both water scarcity and biodiversity impacts is encouraged, together with the use of regionalised impact characterisation methods. Boosting LCA studies on citrus fruits producing countries outside the European Union along with the use of other sustainability tools can support the development of environmental policies. The results of this review can be beneficial for both LCA practitioners and decision-makers, paving the way for a more responsible and sustainable citrus fruit production.

Cushion and working gases mixing during underground gas storage: Role of fractures

Underground gas storage can help realize sustainable energy supply. This process is based on two main elements, namely cushion gas (CG), which serves to retain the reservoir pressure, and the working gas (WG). In a depleted hydrocarbon reservoir, the required base gas constitutes a large portion of total stored gas. Given the high cost of the base gas for a gas storage project, attempts have been made to reduce this cost by replacing some of the base gas by some less expensive alternative. The main challenge arising from such a replacement is that the CG and WG may mix together, with the mixture exhibiting a lower heat value (HV). In this process, reservoir heterogeneity and fractures, in particular, affect the mixing of the two gases significantly. In this research, the effect of fractures and relevant mechanisms in the replacement of the CG and its mixing with the WG in natural gas storage were numerically simulated. The presence of fracture in the reservoir was found to result in three different behaviors in three different time windows. During early days of production, the fractured reservoir produces a gas of a higher HV than that retrieved from the conventional reservoir. Continuing the production process, however, sets the scene for ending up with a higher HV for the gas retrieved from the conventional reservoir rather than the fractured reservoir. The presence of fractures contributes to the sweeping phenomenon in early production stages but rather boosts the gas mixing effect (GME) in the late production stages, while the sequence is reversed when a conventional reservoir is concerned. A comparison between the CO2 and N2 as alternative CGs showed that the N2 tended to disperse in more layers of the reservoir in presence of fractures, resulting in higher degrees of GME across the reservoir.

Biochemical Process and Microbial Evolution in the Conversion of Corn Straw Combined with Coal to Biogas.

The combined anaerobic fermentation of coal and straw can increase the production of biogas. To explore the mechanism of adding corn straw to increase methane production, coal with different metamorphic degrees and corn straw were collected for biogas production simulation experiments under different substrate ratios. The changes in liquid products, the structure of lignocellulose in corn straw, and microbial evolution were monitored. The results showed that the combined fermentation of bituminous coal A with corn straw and bituminous coal C with corn straw at a mass ratio of 2:1 each ((AC-2) and (CC-2)) and that of bituminous coal B and corn straw at a mass ratio of 3:1 (BC-3) had the best gas production, and methane yields reached 17.28, 12.51, and 14.88 mL/g, respectively. The fermentation liquid had organic matter with more types and higher contents during the early and peak stages of gas production, and fewer types of organic matter were detected in the terminal stage. The degradation of lignocelluloses in the corn straw of AC-2 was higher. With the increase in fermentation time, the carbohydrates in the fermentation system increased and the degradation rate of cellulose decreased gradually. The abundance of genes related to nitrate reduction gradually increased, while that of sulfate reduction was on the contrary. Bacteria in the cofermentation system mainly metabolized carbohydrates. During cofermentation with high metamorphic coal, corn straw would be preferentially degraded. The structure of the archaea community changed from Methanosarcina and Methanothrix to Methanobacterium.

Comparison of haematological changes associated with coccidiosis in commercial layer chickens at different production stages in Zaria, Nigeria

Avian coccidiosis remains an economically important disease affecting the poultry industry worldwide. The dearth of information on haematological changes resulting from field cases of coccidiosis in commercial layer chickens necessitated this research. One hundred and twenty commercial layer chickens sampled from different farms in Zaria, diagnosed of coccidiosis at early, mid/peak and late production stages were used for this study. Results showed a significant (p &lt; 0.05) decline in almost all haematological parameters (except for elevated MCV) of commercial layer chickens which were diagnosed of coccidiosis at the different production stages when compared to corresponding values of other apparently healthy layers that served as controls. The mean corpuscular volume (MCV) values in the layers diagnosed of coccidiosis at all production stages were significantly higher than the values obtained from the corresponding apparently healthy ones that served as control, whereas the MCHC showed significant decreases across all layer chickens diagnosed of coccidiosis at different production stages when compared to the corresponding values of the apparently healthy control layers. Thus, the erythrocytic indices of the layer chickens with coccidiosis showed the RBCs were macrocytic and hypochromic. On the basis of mean PCV, layer chickens at early production stage (PCV: 24.51 ± 3.17%) were most severely affected by coccidiosis, following closely by the layers at mid/peak production stage (PCV: 24.66 ± 1.64%). The highest mean WBC (19.15 ± 2.99 x109/L) was recorded in layers with coccidiosis at mid/peak production stage, which showed they were better in mounting inflammatory response when compared to the mean values of layers at early (14.92 ± 2.85 x109/L) and late (17.99 ± 2.70 x109/L) stages of production. In conclusion, coccidiosis in commercial layer chickens caused significant haematological alterations which could necessitate dietary supplementation to prevent occurrence of anaemia and decline in egg production.

Rate Transient Behavior of Wells Intercepting Non-Uniform Fractures in a Layered Tight Gas Reservoir

RTA (Rate Transient Analysis) is a valuable method for obtaining reservoir parameters and well performance, but current RTA models hardly consider the MLVF (Multi-Layer Vertical Fractured) well in a layered tight gas reservoir. To capture the production response caused by the fracture with non-uniform length and conductivity, a novel RTA model for an MLVF well in a layered tight reservoir was presented. In this paper, we present a novel tight gas reservoir RTA model, an extended MLVF well with non-uniform fracture length and conductivity to investigate the production decline feature by the combined RTA type curves. After that, the proposed RTA model is verified to ensure calculation accuracy. Sensitivity analysis is conducted on the crucial parameters, including the formation transmissibility, formation storability, fracture length, fracture conductivity, and fracture extension. Research results show that there are three rate decline stages caused by a multi fracture with non-uniform conductivity. The wellbore storage and formation skin can be ignored in the rate transient analysis work. The formation transmissibility affects the rate transient response more than the formation storability. The increase in fracture length, fracture conductivity, and the extension of a high conductivity fracture will improve the well’s production rate in a tight gas reservoir’s early production stage. Therefore, it is significant to incorporate how the effects of the MLVF well intercepting with non-uniform length fractures change conductivity. The RTA model proposed in this paper enables us to better evaluate well performance and capture the formation of complex fracture characteristics in a layered tight gas reservoir based on rate transient data.

Interview with Dr Minshad Ansari, Founder and CEO of Bionema Ltd

Bionema is a leading UK biopesticide technology developer. We create chemical-free, pest management solutions for the horticulture, turf &amp; amenity, landscaping, and forestry sectors. We have more than 30 years' experience in research, development, and the commercialisation of biopesticides. The company was founded in 2012 by Dr Minshad Ansari, a former academic who had already worked at research institutions across India, Belgium, and the UK. He joined Swansea University in 2005 and started working on the development of biopesticides for the control of insect pests in the horticulture and forestry sectors. When he visited growers and farmers, he was often asked about pest control methods that did not require the extensive use of chemical solutions. These queries made him investigate the development of non-toxic, natural methods of pest control that would reduce the need for chemical use. Once Dr Ansari developed his thinking around biopesticide alternatives, he set up Bionema in 2012 a spinout from Swansea University. The focus of Bionema's research was the development and commercialisation of naturally occurring microorganisms for crop protection against pests and diseases thereby reducing the use of synthetic pesticides, enhancing food security, and increasing crop yields. The company established its headquarters at the Institute of Life Science at Swansea University in the UK. In 2017, Bionema made a breakthrough discovery in the development of NemaTrident, a tri-component patented solution, and the conception of the microencapsulation formulation delivery system in 2018 for foliar challenges. Shortly afterwards, Dr Ansari raised £680,000 equity investment and received £1.1 million in grant funding from Innovate UK and the Welsh Government which was used for the development and commercialisation of UniSporeG, a unique fungal bioinsecticide for weevil control in soft fruits. Innovation in biopesticide formulations is a core objective for Bionema, enabling the company to commercialise multiple product lines and to generate a pipeline of advanced and early-stage products that include beneficial nematicides, bioinsecticides, compatible surfactants and delivery platforms. Bionema has also developed a robust patent portfolio and collected a library of more than a hundred commercially viable microorganisms for pipeline candidates.

Experimental study on sand control gravel particle gradation optimization in mud hydrate reservoir

Sand production significantly influences the safety and stability of gas hydrate exploitation in reservoirs with high mud content. Gravel packing is an effective method for sand control. The median grain size ratio (D50/d50) values and fine particle content of gravel pack are important factors in sand control during natural gas hydrate exploitation. This paper focuses on the sand blocking effect and permeability characteristics of different grades of gravel. The sand retention test was carried out on four samples with different ratios. The optimal D50/d50 value and fine particle content for gas hydrate production were obtained. A laser particle size analyzer and geotechnical test found the reservoir and gravel layer pore structure change. The results show that the optimal GSR was 24.5, and the optimal fine particle content was about 38%. The permeability decline of the gravel layer occurs in the early stage of production, and the fine particles in the gravel will slow down the degree of seepage damage. For gravel with the same particle size range and different median particle sizes, it has little effect on sand control accuracy but mainly on permeability. The research in this paper can provide a reference for selecting sand control gravel for natural gas exploitation in marine areas.

A Quality by Design Approach to Microbial Retention Validation.

Regulatory and manufacturing requirements exist for performance of product-specific microbial retention testing on sterilizing filters. The implementation of a Quality by Design approach to sterilizing filtration supports a paradigm that would obviate the need for product-specific testing for early-stage products that do not have the quantity of material required to perform such testing easily and efficiently. Process and product parameters were varied to determine their effect on microbial retention to define a design space. To minimize the burden of filter validation retention studies for early-stage (Phase 1) manufacturing, it is recommended that manufacturers perform a risk assessment to confirm their product and process conditions are within the established design space. For later stage product development prior to marketing authorization, product-specific filter validation testing is expected.