Multi-objective biopharma capacity planning under uncertainty using a flexible genetic algorithm approach

This paper presents a flexible genetic algorithm optimisation approach for multi-objective biopharmaceutical planning problems under uncertainty. The optimisation approach combines a continuous-time heuristic model of a biopharmaceutical manufacturing process, a variable-length multi-objective genetic algorithm, and Graphics Processing Unit (GPU)-accelerated Monte Carlo simulation. The proposed approach accounts for constraints and features such as rolling product sequence-dependent changeovers, multiple intermediate demand due dates, product QC/QA release times, and pressure to meet uncertain product demand on time. An industrially-relevant case study is used to illustrate the functionality of the approach. The case study focused on optimisation of conflicting objectives, production throughput, and product inventory levels, for a multi-product biopharmaceutical facility over a 3-year period with uncertain product demand. The advantages of the multi-objective GA with the embedded Monte Carlo simulation were demonstrated by comparison with a deterministic GA tested with Monte Carlo simulation post-optimisation

Fast genetic algorithm approaches to solving discrete-time mixed integer linear programming problems of capacity planning and scheduling of biopharmaceutical manufacture

The previous research work in the literature for capacity planning and scheduling of biopharmaceutical manufacture focused mostly on the use of mixed integer linear programming (MILP). This paper presents fast genetic algorithm (GA) approaches for solving discrete-time MILP problems of capacity planning and scheduling in the biopharmaceutical industry. The proposed approach is validated on two case studies from the literature and compared with MILP models. In case study 1, a medium-term capacity planning problem of a single-site, multi-suite, multi-product biopharmaceutical manufacture is presented. The GA is shown to achieve the global optimum on average 3.6 times faster than a MILP model. In case study 2, a larger long-term planning problem of multi-site, multi-product bio-manufacture is solved. Using the rolling horizon strategy, the GA is demonstrated to achieve near-optimal solutions (1% away from the global optimum) as fast as a MILP model

Modern day monitoring and control challenges outlined on an industrial-scale benchmark fermentation process

This paper outlines real-world control challenges faced by modern-day biopharmaceutical facilities through the extension of a previously developed industrial-scale penicillin fermentation simulation (IndPenSim). The extensions include the addition of a simulated Raman spectroscopy device for the purpose of developing, evaluating and implementation of advanced and innovative control solutions applicable to biotechnology facilities. IndPenSim can be operated in fixed or operator controlled mode and generates all the available on-line, off-line and Raman spectra for each batch. The capabilities of IndPenSim were initially demonstrated through the implementation of a QbD methodology utilising the three stages of the PAT framework. Furthermore, IndPenSim evaluated a fault detection algorithm to detect process faults occurring on different batches recorded throughout a yearly campaign. The simulator and all data presented here are available to download at www.industrialpenicillinsimulation.com and acts as a benchmark for researchers to analyse, improve and optimise the current control strategy implemented on this facility. Additionally, a highly valuable data resource containing 100 batches with all available process and Raman spectroscopy measurements is freely available to download. This data is highly suitable for the development of big data analytics, machine learning (ML) or artificial intelligence (AI) algorithms applicable to the biopharmaceutical industry

Features of the porous morphology of anodic alumina films at the initial stage of disordered growth

A characteristic feature of disordered porous anodic film growth at the initial stage of aluminum anodizing was revealed by varying the electrolyte type and anodizing voltage. The samples were obtained by the electrochemical oxidation of thin aluminum films (100 nm thick) on SiO2/Si substrates in a 0.3 M oxalic acid at 10–50 V and were studied by SEM. The ImageJ analysis of the images revealed the simultaneous development of two large groups of pores: major pores with a large diameter and minor pores with a smaller diameter. When anodizing in oxalic acid at 10–50 V, it has been shown that the ratio of the diameters of the major and minor pores remains constant and is about 1.17. Using a geometric model, we demonstrated that the centers of the minor pores are located inside the elementary hexagonal cell formed by the centers of the major pores. Moreover, our results are very close to the theoretical value of 2/√3. At the initial stage of disordered pore growth, the development of minor pores rather than major pores is not a random process and is determined by energy-efficient conditions for the development of pores inside the hexagonal cells formed by the major pores. The increase in compressive mechanical stress in the anodic film leads to an interruption in the development of such pores

Genetic discontinuity between local hunter-gatherers and Europes first farmers

Following the domestication of animals and crops in the Near East some 11,000 years ago, farming reached much of Central Europe by 7,500 before present. The extent to which these early European farmers ere immigrants, or descendants of resident hunter-gatherers who had learnt farming, has been widely debated. We compare new mitochondrial DNA (mtDNA) sequences from late European hunter-gatherer skeletons with those from early farmers, and from modern Europeans. We find large genetic differences betwee all three groups that cannot be explained by population continuity alone. Most (82 %) of the ancient hunter-gatherers share mtDNA types that are relatively rare in Central Europeans today. Together, thse analyses provide persuasive evidence that the first farmers were not the descendants of local hunergatherers but immigrated into Central Europe at the onset of the Neolithic

Study on the performance of different craniofacial superimposition approaches (II): Best practices proposal

Craniofacial superimposition, although existing for one century, is still a controversial technique within the scientific community. Objective and unbiased validation studies over a significant number of cases are required to establish a more solid picture on the reliability. However, there is lack of protocols and standards in the application of the technique leading to contradictory information concerning reliability. Instead of following a uniform methodology, every expert tends to apply his own approach to the problem, based on the available technology and deep knowledge on human craniofacial anatomy, soft tissues, and their relationships. The aim of this study was to assess the reliability of different craniofacial superimposition methodologies and the corresponding technical approaches to this type of identification. With all the data generated, some of the most representative experts in craniofacial identification joined in a discussion intended to identify and agree on the most important issues that have to be considered to properly employ the craniofacial superimposition technique. As a consequence, the consortium has produced the current manuscript, which can be considered the first standard in the field; including good and bad practices, sources of error and uncertainties, technological requirements and desirable features, and finally a common scale for the craniofacial matching evaluation. Such a document is intended to be part of a more complete framework for craniofacial superimposition, to be developed during the FP7-founded project MEPROCS, which will favour and standardize its proper application

Utilising biological geotextiles: Introduction to the BORASSUS project and global perspectives

Field and laboratory studies indicate that utilisation of biological geotextiles constructed from palm-leaves and other selected organic materials are an effective, sustainable and economically viable soil conservation technique. The three-year plus (1 July 2005–28 February 2009) EU-funded BORASSUS Project (contract no. INCO-CT-2005-510745) evaluated the long-term effectiveness of biological geotextiles in controlling soil erosion and assessing their sustainability and economic viability. These studies progressed in ten countries, both in the ‘industrial north’ (in Europe) and in the ‘developing south’ (Africa, South America and South East Asia). The studied countries in the ‘developing south’ included Brazil, China, The Gambia, South Africa, Thailand and Vietnam. The ‘industrial north’ countries included Belgium, Hungary, Lithuania and the UK. The main findings of these studies are summarised in this paper and thematic information is presented in the other four papers in this Special Issue. Biological geotextiles offer potentially novel bioengineering solutions to environmental problems, including technologies for soil conservation, sustainable plant production and use of indigenous plants, improved ecosystem management by decreasing deforestation, improving agroforestry and cost-effective biogeotextile applications in diverse environments. Biogeotextiles may provide socio-economic platforms for sustainable development and the benefits for developing countries may include poverty alleviation, engagement of local people as stakeholders, employment for disadvantaged groups, small and medium enterprise (SME) development, earning hard currency, environmental education and local community involvement in land reclamation and environmental education programmes. These benefits are achieved through: (i) promotion of sustainable and environmentally friendly palm-agriculture to discourage deforestation, promoting both reforestation and agroforestry; (ii) construction of biogeotextiles enabling development of a rural labour-intensive industry, particularly encouraging employment of socially disadvantaged groups and (iii) export of biogeotextiles to industrialised countries could earn hard currency for developing economies, based on the principles of fair trade. Research and development activities of the BORASSUS Project have improved our knowledge on the effect of biogeotextile mats on the micro- and macro-soil environments and at larger scales through controlled laboratory and field experiments in diverse environments

An integrative skeletal and paleogenomic analysis of stature variation suggests relatively reduced health for early european farmers

Human culture, biology, and health were shaped dramatically by the onset of agriculture ∼12,000 y B.P. This shift is hypothesized to have resulted in increased individual fitness and population growth as evidenced by archaeological and population genomic data alongside a decline in physiological health as inferred from skeletal remains. Here, we consider osteological and ancient DNA data from the same prehistoric individuals to study human stature variation as a proxy for health across a transition to agriculture. Specifically, we compared “predicted” genetic contributions to height from paleogenomic data and “achieved” adult osteological height estimated from long bone measurements for 167 individuals across Europe spanning the Upper Paleolithic to Iron Age (∼38,000 to 2,400 B.P.). We found that individuals from the Neolithic were shorter than expected (given their individual polygenic height scores) by an average of −3.82 cm relative to individuals from the Upper Paleolithic and Mesolithic (P = 0.040) and −2.21 cm shorter relative to post-Neolithic individuals (P = 0.068), with osteological vs. expected stature steadily increasing across the Copper (+1.95 cm relative to the Neolithic), Bronze (+2.70 cm), and Iron (+3.27 cm) Ages. These results were attenuated when we additionally accounted for genome-wide genetic ancestry variation: for example, with Neolithic individuals −2.82 cm shorter than expected on average relative to pre-Neolithic individuals (P = 0.120). We also incorporated observations of paleopathological indicators of nonspecific stress that can persist from childhood to adulthood in skeletal remains into our model. Overall, our work highlights the potential of integrating disparate datasets to explore proxies of health in prehistory.info:eu-repo/semantics/publishedVersio

A 300-year record of sedimentation in a small tilled catena in Hungary based on δ13C, δ15N, and C/N distribution

Purpose Soil erosion is one of the most serious hazards that endanger sustainable food production. Moreover, it has marked effects on soil organic carbon (SOC) with direct links to global warming. At the same time, soil organic matter (SOM) changes in composition and space could influence these processes. The aim of this study was to predict soil erosion and sedimentation volume and dynamics on a typical hilly cropland area of Hungary due to forest clearance in the early eighteenth century. Materials and methods Horizontal soil samples were taken along two parallel intensively cultivated complex convex-concave slopes from the eroded upper parts at mid-slope positions and from sedimentation in toe-slopes. Samples were measured for SOC, total nitrogen (TN) content, and SOMcompounds (δ13C, δ15N, and photometric indexes). They were compared to the horizons of an in situ non-eroded profile under continuous forest. On the depositional profile cores, soil depth prior to sedimentation was calculated by the determination of sediment thickness. Results and discussion Peaks of SOC in the sedimentation profiles indicated thicker initial profiles, while peaks in C/N ratio and δ13C distribution showed the original surface to be ~ 20 cm lower. Peaks of SOC were presumed to be the results of deposition of SOC-enriched soil from the upper slope transported by selective erosion of finer particles (silts and clays). Therefore, changes in δ13C values due to tillage and delivery would fingerprint the original surface much better under the sedimentation scenario than SOC content. Distribution of δ13C also suggests that the main sedimentation phase occurred immediately after forest clearance and before the start of intense cultivation with maize. Conclusions This highlights the role of relief in sheet erosion intensity compared to intensive cultivation. Patterns of δ13C indicate the original soil surface, even in profiles deposited as sediment centuries ago. The δ13C and C/N decrease in buried in situ profiles had the same tendency as recent forest soil, indicating constant SOM quality distribution after burial. Accordingly, microbiological activity, root uptake, and metabolism have not been effective enough to modify initial soil properties

Palaeogenomics of Upper Palaeolithic to Neolithic European hunter-gatherers

Modern humans have populated Europe for more than 45,000 years1,2. Our knowledge of the genetic relatedness and structure of ancient hunter-gatherers is however limited, owing to the scarceness and poor molecular preservation of human remains from that period3. Here we analyse 356 ancient hunter-gatherer genomes, including new genomic data for 116 individuals from 14 countries in western and central Eurasia, spanning between 35,000 and 5,000 years ago. We identify a genetic ancestry profile in individuals associated with Upper Palaeolithic Gravettian assemblages from western Europe that is distinct from contemporaneous groups related to this archaeological culture in central and southern Europe4, but resembles that of preceding individuals associated with the Aurignacian culture. This ancestry profile survived during the Last Glacial Maximum (25,000 to 19,000 years ago) in human populations from southwestern Europe associated with the Solutrean culture, and with the following Magdalenian culture that re-expanded northeastward after the Last Glacial Maximum. Conversely, we reveal a genetic turnover in southern Europe suggesting a local replacement of human groups around the time of the Last Glacial Maximum, accompanied by a north-to-south dispersal of populations associated with the Epigravettian culture. From at least 14,000 years ago, an ancestry related to this culture spread from the south across the rest of Europe, largely replacing the Magdalenian-associated gene pool. After a period of limited admixture that spanned the beginning of the Mesolithic, we find genetic interactions between western and eastern European hunter-gatherers, who were also characterized by marked differences in phenotypically relevant variants