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Background and Aims Upscaling carbon allocation requires knowledge of the variability at the scales at which data are collected and applied. Trees exhibit different growth rates and timings of wood formation. However, the factors explaining these differences remain undetermined, making samplings and estimations of the growth dynamics a complicated task, habitually based on technical rather than statistical reasons. This study explored the variability in xylem phenology among 159 balsam firs [ Abies balsamea (L.) Mill.]. Methods Wood microcores were collected weekly from April to October 2018 in a natural stand in Quebec, Canada, to detect cambial activity and wood formation timings. We tested spatial autocorrelation, tree size and cell production rates as explanatory variables of xylem phenology. We assessed sample size and margin of error for wood phenology assessment at different confidence levels. Key Results Xylem formation lasted between 40 and 110 d, producing between 12 and 93 cells. No effect of spatial proximity or size of individuals was detected on the timings of xylem phenology. Trees with larger cell production rates showed a longer growing season, starting xylem differentiation earlier and ending later. A sample size of 23 trees produced estimates of xylem phenology at a confidence level of 95 % with a margin of error of 1 week. Conclusions This study highlighted the high variability in the timings of wood formation among trees within an area of 1 km2. The correlation between the number of new xylem cells and the growing season length suggests a close connection between the processes of wood formation and carbon sequestration. However, the causes of the observed differences in xylem phenology remain partially unresolved. We point out the need to carefully consider sample size when assessing xylem phenology to explore the reasons underlying this variability and to allow reliable upscaling of carbon allocation in forests. [ABSTRACT FROM AUTHOR]

Abstract Background The major fleshy tissues of the apple fruit are spatially separable into cortex and pith. These tissues display differential growth during development. Key features of such differential growth, and sink metabolic programs supporting it have not been investigated previously. We hypothesized that differential growth between these fruit tissues is supported by differential sink metabolic programs, particularly during early development. Growth, metabolite concentrations, and transcript abundance of metabolism-related genes were measured to determine characteristics of differential growth and their underlying metabolic programs. Results The cortex displayed > 5-fold higher growth than the pith during early fruit development, indicating that differential growth was established during this period. Further, when resource availability was increased through sink-removal, cortex growth was preferentially enhanced. Greatest diversity in metabolic programs between these tissues was evident during early fruit development. Higher cortex growth during early development was facilitated by increased catabolism of imported carbon (C) resources, sorbitol and sucrose, and the nitrogen (N) resource, asparagine. It was also associated with enhanced primary C metabolism, and C storage as malate and quinate. The pith metabolic program during this period involved limited allocation of C and N to growth, but greater allocation to storage, and enhanced sucrose-sucrose cycling. Conclusions Together, these data indicate that the fruit cortex tissue displays a resource intensive metabolic program during early fruit development. This provides the C backbones, proteins, energy and osmolytes to support its higher growth.

While human induced pluripotent stem cells (hiPSCs) provide novel prospects for disease-modeling, the high phenotypic variability seen across different lines demands usage of large hiPSC cohorts to decipher the impact of individual genetic variants. Thus, a much higher grade of parallelization, and throughput in the production of hiPSCs is needed, which can only be achieved by implementing automated solutions for cell reprogramming, and hiPSC expansion. Here, we describe the StemCellFactory, an automated, modular platform covering the entire process of hiPSC production, ranging from adult human fibroblast expansion, Sendai virus-based reprogramming to automated isolation, and parallel expansion of hiPSC clones. We have developed a feeder-free, Sendai virus-mediated reprogramming protocol suitable for cell culture processing via a robotic liquid handling unit that delivers footprint-free hiPSCs within 3 weeks with state-of-the-art efficiencies. Evolving hiPSC colonies are automatically detected, harvested, and clonally propagated in 24-well plates. In order to ensure high fidelity performance, we have implemented a high-speed microscope for in-process quality control, and image-based confluence measurements for automated dilution ratio calculation. This confluence-based splitting approach enables parallel, and individual expansion of hiPSCs in 24-well plates or scale-up in 6-well plates across at least 10 passages. Automatically expanded hiPSCs exhibit normal growth characteristics, and show sustained expression of the pluripotency associated stem cell marker TRA-1-60 over at least 5 weeks (10 passages). Our set-up enables automated, user-independent expansion of hiPSCs under fully defined conditions, and could be exploited to generate a large number of hiPSC lines for disease modeling, and drug screening at industrial scale, and quality.

Reactive oxygen species (ROS) can act as signaling molecules involved in the acclimation of plants to various abiotic and biotic stresses. However, it is not clear how the generalized increases in ROS and downstream signaling events that occur in response to stressful conditions are coordinated to modify plant growth and development. Previous studies of maize (Zea mays L.) primary root growth under water deficit stress showed that cell elongation is maintained in the apical region of the growth zone but progressively inhibited further from the apex, and that the rate of cell production is also decreased. It was observed that apoplastic ROS, particularly hydrogen peroxide (H2O2), increased specifically in the apical region of the growth zone under water stress, resulting at least partly from increased oxalate oxidase activity in this region. To assess the function of the increase in apoplastic H2O2 in root growth regulation, transgenic maize lines constitutively expressing a wheat oxalate oxidase were utilized in combination with kinematic growth analysis to examine effects of increased apoplastic H2O2 on the spatial pattern of cell elongation and on cell production in well-watered and water-stressed roots. Effects of H2O2 removal (via scavenger pretreatment) specifically from the apical region of the growth zone were also assessed. The results show that apoplastic H2O2 positively modulates cell production and root elongation under well-watered conditions, whereas the normal increase in apoplastic H2O2 in water-stressed roots is causally related to down-regulation of cell production and root growth inhibition. The effects on cell production were accompanied by changes in spatial profiles of cell elongation and in the length of the growth zone. However, effects on overall cell elongation, as reflected in final cell lengths, were minor. These results reveal a fundamental role of apoplastic H2O2 in regulating cell production and root elongation in both well-watered and water-stressed conditions.

Reactive oxygen species (ROS) can act as signaling molecules involved in the acclimation of plants to various abiotic and biotic stresses. However, it is not clear how the generalized increases in ROS and downstream signaling events that occur in response to stressful conditions are coordinated to modify plant growth and development. Previous studies of maize (Zea mays L.) primary root growth under water deficit stress showed that cell elongation is maintained in the apical region of the growth zone but progressively inhibited further from the apex, and that the rate of cell production is also decreased. It was observed that apoplastic ROS, particularly hydrogen peroxide (H2O2), increased specifically in the apical region of the growth zone under water stress, resulting at least partly from increased oxalate oxidase activity in this region. To assess the function of the increase in apoplastic H2O2 in root growth regulation, transgenic maize lines constitutively expressing a wheat oxalate oxidase were utilized in combination with kinematic growth analysis to examine effects of increased apoplastic H2O2 on the spatial pattern of cell elongation and on cell production in well-watered and water-stressed roots. Effects of H2O2 removal (via scavenger pretreatment) specifically from the apical region of the growth zone were also assessed. The results show that apoplastic H2O2 positively modulates cell production and root elongation under well-watered conditions, whereas the normal increase in apoplastic H2O2 in water-stressed roots is causally related to down-regulation of cell production and root growth inhibition. The effects on cell production were accompanied by changes in spatial profiles of cell elongation and in the length of the growth zone. However, effects on overall cell elongation, as reflected in final cell lengths, were minor. These results reveal a fundamental role of apoplastic H2O2 in regulating cell production and root elongation in both well-watered and water-stressed conditions. [ABSTRACT FROM AUTHOR]

Background: The major fleshy tissues of the apple fruit are spatially separable into cortex and pith. These tissues display differential growth during development. Key features of such differential growth, and sink metabolic programs supporting it have not been investigated previously. We hypothesized that differential growth between these fruit tissues is supported by differential sink metabolic programs, particularly during early development. Growth, metabolite concentrations, and transcript abundance of metabolism-related genes were measured to determine characteristics of differential growth and their underlying metabolic programs. Results: The cortex displayed > 5-fold higher growth than the pith during early fruit development, indicating that differential growth was established during this period. Further, when resource availability was increased through sink-removal, cortex growth was preferentially enhanced. Greatest diversity in metabolic programs between these tissues was evident during early fruit development. Higher cortex growth during early development was facilitated by increased catabolism of imported carbon (C) resources, sorbitol and sucrose, and the nitrogen (N) resource, asparagine. It was also associated with enhanced primary C metabolism, and C storage as malate and quinate. The pith metabolic program during this period involved limited allocation of C and N to growth, but greater allocation to storage, and enhanced sucrose-sucrose cycling. Conclusions: Together, these data indicate that the fruit cortex tissue displays a resource intensive metabolic program during early fruit development. This provides the C backbones, proteins, energy and osmolytes to support its higher growth. [ABSTRACT FROM AUTHOR]

Many data are available on expansion protocols for mesenchymal stromal cells (MSCs) for both experimental settings and manufacturing for clinical trials. However, there is a lack of information on translation of established protocols for Good Manufacturing Practice (GMP) from validation to manufacturing for clinical application. We present the validation and translation of a standardized pre-clinical protocol for isolation and expansion of MSCs for a clinical trial for reconstitution of alveolar bone. Key parameters of 22 large-scale expansions of MSCs from bone marrow (BM) for validation were compared with 11 expansions manufactured for the clinical trial "Jaw bone reconstruction using a combination of autologous mesenchymal stromal cells and biomaterial prior to dental implant placement (MAXILLO1)" aimed at reconstruction of alveolar bone. Despite variations of the starting material, the robust protocol led to stable performance characteristics of expanded MSCs. Manufacturing of the autologous advanced therapy medicinal product MAXILLO-1-MSC was possible, requiring 21 days for each product. Transport of BM aspirates and MSCs within 24 h was guaranteed. MSCs fulfilled quality criteria requested by the national competent authority. In one case, the delivered MSCs developed a mosaic in chromosomal finding, showing no abnormality in differentiation capacity, growth behavior or surface marker expression during long-term culture. The proportion of cells with the mosaic decreased in long-term culture and cells stopped growth after 38.4 population doublings. Clinical use of freshly prepared MSCs, manufactured according to a standardized and validated protocol, is feasible for bone regeneration, even if there was a long local distance between manufacturing center and clinical site. Several parameters, such as colony forming units fibroblasts (CFU-F), percentage of CD34+ cells, cell count of mononuclear cells (MNCs) and white blood cells (WBCs), of the BM may serve as a predictive tool for the yield of MSCs and may help to avoid unnecessary costs for MSC manufacturing due to insufficient cell expansion rates. [ABSTRACT FROM AUTHOR]

Purpose: In this paper, we have proposed a new model for designing a Cellular Manufacturing System (CMS) for minimizing the costs regarding a limited number of cells to be formed by assigning workforce. Design/methodology/approach: Pursuing mathematical approach and because the problem is NP-Hard, two meta-heuristic methods of Simulated Annealing (SA) and Particle Swarm Optimization (PSO) algorithms have been used. A small randomly generated test problem with real-world dimensions has been solved using simulated annealing and particle swarm algorithms. Findings: The quality of the two algorithms has been compared. The results showed that PSO algorithm provides more satisfactory solutions than SA algorithm in designing a CMS under uncertainty demands regarding the workforce allocation. Originality/value: In the most of the previous research, cell production has been considered under certainty production or demand conditions, while in practice production and demand are in a dynamic situations and in the real settings, cell production problems require variables and active constraints for each different time periods to achieve better design, so modeling such a problem in dynamic structure leads to more complexity while getting more applicability. The contribution of this paper is providing a new model by considering dynamic production times and uncertainty demands in designing cells. [ABSTRACT FROM AUTHOR]

The adoptive transfer of chimeric antigen receptor (CAR)-modified T cells is attracting growing interest for the treatment of malignant diseases. Early trials with anti-CD19 CAR T cells have achieved spectacular remissions in B-cell leukemia and lymphoma, so far refractory, very recently resulting in the Food and Drug Administration approval of CD19 CAR T cells for therapy. With further applications and increasing numbers of patients, the reproducible manufacture of high-quality clinical-grade CAR T cells is becoming an ever greater challenge. New processing techniques, quality-control mechanisms, and logistic developments are required to meet both medical needs and regulatory restrictions. This paper summarizes the state-of-the-art in manufacturing CAR T cells and the current challenges that need to be overcome to implement this type of cell therapy in the treatment of a variety of malignant diseases and in a greater number of patients. [ABSTRACT FROM AUTHOR]

Sandy surface sediments of tidal flats exhibit high microbial activity due to the fast and deep-reaching transport of oxygen and nutrients by porewater advection. On the other hand during low tide, limited transport results in nutrient and oxygen depletion concomitant to the accumulation of microbial metabolites. This study represents the first attempt to use flow-through reactors to investigate virus production, virus transport and the impact of tides and season in permeable sediments. The reactors were filled with intertidal sands of two sites (North beach site and backbarrier sand flat of Spiekeroog island in the German Wadden Sea) to best simulate advective porewater transport through the sediments. Virus and cell release along with oxygen consumption were measured in the effluents of reactors during continuous flow of water through the sediments as well as in tidal simulation experiments where alternating cycles with and without water flow (each for 6 h) were operated. The results showed net rates of virus production (0.3–13.2 × 106 viruses cm−3 h−1) and prokaryotic cell production (0.3–10.0 × 105 cells cm−3 h−1) as well as oxygen consumption rates (56–737 μmol l−1 h−1) to be linearly correlated reflecting differences in activity, season and location of the sediments. Calculations show that total virus turnover was fast with 2 to 4 days, whereas virus-mediated cell turnover was calculated to range between 5–13 or 33–91 days depending on the assumed burst sizes (number of viruses released upon cell lysis) of 14 or 100 viruses, respectively. During the experiments, the homogenized sediments in the reactors became vertically structured with decreasing microbial activities and increasing impact of viruses on prokaryotic mortality with depth. Tidal simulation clearly showed a strong accumulation of viruses and cells in the top sections of the reactors when the flow was halted indicating a consistently high virus production during low tide. In conclusion, cell lysis products due to virus production may fuel microbial communities in the absence of advection-driven nutrient input, but are eventually washed off the surface sediment during high tide and being transported into deeper sediment layers or into the water column together with the produced viruses.

Sandy surface sediments of tidal flats exhibit high microbial activity due to the fast and deep-reaching transport of oxygen and nutrients by porewater advection. On the other hand during low tide, limited transport results in nutrient and oxygen depletion concomitant to the accumulation of microbial metabolites. This study represents the first attempt to use flow-through reactors to investigate virus production, virus transport and the impact of tides and season in permeable sediments. The reactors were filled with intertidal sands of two sites (North beach site and backbarrier sand flat of Spiekeroog island in the German Wadden Sea) to best simulate advective porewater transport through the sediments. Virus and cell release along with oxygen consumption were measured in the effluents of reactors during continuous flow of water through the sediments as well as in tidal simulation experiments where alternating cycles with and without water flow (each for 6 h) were operated. The results showed net rates of virus production (0.3-13.2 × 106 viruses cm-3 h-1) and prokaryotic cell production (0.3-10.0 × 105 cells cm-3 h-1) as well as oxygen consumption rates (56-737 µmol l-1 h-1) to be linearly correlated reflecting differences in activity, season and location of the sediments. Calculations show that total virus turnover was fast with 2 to 4 days, whereas virus-mediated cell turnover was calculated to range between 5-13 or 33-91 days depending on the assumed burst sizes (number of viruses released upon cell lysis) of 14 or 100 viruses, respectively. During the experiments, the homogenized sediments in the reactors became vertically structured with decreasing microbial activities and increasing impact of viruses on prokaryotic mortality with depth. Tidal simulation clearly showed a strong accumulation of viruses and cells in the top sections of the reactors when the flow was halted indicating a consistently high virus production during low tide. In conclusion, cell lysis products due to virus production may fuel microbial communities in the absence of advection-driven nutrient input, but are eventually washed off the surface sediment during high tide and being transported into deeper sediment layers or into the water column together with the produced viruses. [ABSTRACT FROM AUTHOR]

The demands placed on automation of cell production processes for IT products are becoming increasingly sophisticated. Dual-arm robots are drawing particular attention as a process solution because they offer flexibility and can work in a similar manner to a human operator. In this paper, we propose an automation system for cellular phone packing processes that uses two dual-arm robots. The applied robots are designed with specifications that meet the requirements of the cellular phone packing tasks. In addition, a robotic cell production system is proposed that applies a task allocation method to perform an efficient packing job for cellular phones. In particular, each task is assigned with the intention of reducing the takt time , which is the time taken to finish a single product in the production line and to avoid collisions between the two robots. Finally, we implement some of our results in a demonstration of a packing job that involves filling five unit boxes with seven kinds of accessories. [ABSTRACT FROM AUTHOR]

Purpose: This research, by using the SIMIO simulation platform, provides a quantitative and comparative analysis of how the efficiency of four different cell production modes is affected. It is hoped that the results will be of some help for garment factories to optimize their production lines. Design/methodology/approach: The SIMIO simulation platform was employed in the research and comparisons were made of the simulation test results about the four popular cellular manufacturing modes. Findings: The operation mode, number of operators, and number of buffer areas are key factors affecting the production line efficiency, and need to be reasonably set to achieve the highest efficiency. Originality/value: As most research literature so far is qualitative, this research provided a simulation-based quantitative analysis of the production efficiency under different cell production modes. [ABSTRACT FROM AUTHOR]

Background and Aims Ongoing global warming has been implicated in shifting phenological patterns such as the timing and duration of the growing season across a wide variety of ecosystems. Linear models are routinely used to extrapolate these observed shifts in phenology into the future and to estimate changes in associated ecosystem properties such as net primary productivity. Yet, in nature, linear relationships may be special cases. Biological processes frequently follow more complex, non-linear patterns according to limiting factors that generate shifts and discontinuities, or contain thresholds beyond which responses change abruptly. This study investigates to what extent cambium phenology is associated with xylem growth and differentiation across conifer species of the northern hemisphere. Methods Xylem cell production is compared with the periods of cambial activity and cell differentiation assessed on a weekly time scale on histological sections of cambium and wood tissue collected from the stems of nine species in Canada and Europe over 1–9 years per site from 1998 to 2011. Key Results The dynamics of xylogenesis were surprisingly homogeneous among conifer species, although dispersions from the average were obviously observed. Within the range analysed, the relationships between the phenological timings were linear, with several slopes showing values close to or not statistically different from 1. The relationships between the phenological timings and cell production were distinctly non-linear, and involved an exponential pattern Conclusions The trees adjust their phenological timings according to linear patterns. Thus, shifts of one phenological phase are associated with synchronous and comparable shifts of the successive phases. However, small increases in the duration of xylogenesis could correspond to a substantial increase in cell production. The findings suggest that the length of the growing season and the resulting amount of growth could respond differently to changes in environmental conditions. [ABSTRACT FROM AUTHOR]

Although habitually considered as a whole, xylogenesis is a complex process of division and maturation of a pool of cells where the relationship between the phenological phases generating such a growth pattern remains essentially unknown. This study investigated the causal relationships in cambium phenology of black spruce [Picea mariana (Mill.) BSP] monitored for 8 years on four sites of the boreal forest of Quebec, Canada. The dependency links connecting the timing of xylem cell differentiation and cell production were defined and the resulting causal model was analysed with d-sep tests and generalized mixed models with repeated measurements, and tested with Fisher’s C statistics to determine whether and how causality propagates through the measured variables. The higher correlations were observed between the dates of emergence of the first developing cells and between the ending of the differentiation phases, while the number of cells was significantly correlated with all phenological phases. The model with eight dependency links was statistically valid for explaining the causes and correlations between the dynamics of cambium phenology. Causal modelling suggested that the phenological phases involved in xylogenesis are closely interconnected by complex relationships of cause and effect, with the onset of cell differentiation being the main factor directly or indirectly triggering all successive phases of xylem maturation. [ABSTRACT FROM PUBLISHER]

Xylogenesis was monitored during 2003 and 2004 in a timberline environment in southern Italy to assess links between temperature, cambial phenology and wood formation on a short-time scale. Wood microcores were collected weekly from May to October from 10 trees of Pinus leucodermis Ant., histological sections were cut with a rotary microtome and anatomical features of the developing and mature tracheids were observed and measured along the growing tree ring. Spring 2003 was hotter than spring 2004, with temperatures up to 2.6 °C above historical means. The hotter conditions resulted in an earlier onset of cambial activity and all differentiation phases of about 20 days, resulting in an increased duration of xylogenesis of about 23 days. Air and stem temperatures at which xylogenesis had a 0.5 probability of being active were calculated with logistic regressions fitted on binary responses. In both years, similar thresholds were estimated with daily mean values of 8.2 and 9.5 °C for air and stem temperatures, respectively. The observed convergent responses of cambium phenology to temperature during the two contrasting springs confirm the key role of this environmental factor in determining the onset and duration of wood formation in timberline areas. The intra-annual dynamics of ring-width increase differed between years, with significantly narrower rings formed in 2004 than in 2003. These differences were mainly related to cell size because larger earlywood tracheids were produced in 2003. This study demonstrates the plasticity of tree-ring formation in response to high temperatures as a result of modifications in the onset and duration of differentiation. [ABSTRACT FROM PUBLISHER]

Leaf growth in grasses is determined by the cell division and elongation rates, with the duration of cell elongation being one of the processes that is the most sensitive to salinity. Our objective was to investigate the distribution profiles of cell production, cell length and the duration of cell elongation in the growing zone of the wheat leaf during the steady growth phase. Plants were grown in loamy soil with or without 120 mmol/L NaCl in a growth chamber, and harvested at day 3 after leaf 4 emerged. Results show that the elongation rate of leaf 4 was reduced by 120 mmol/L NaCl during the steady growth phase. The distribution profile of the lengths of abaxial epidermal cells of leaf 4 during the steady growth stage shows a sigmoidal pattern along the leaf axis for both treatments. Although salinity did not affect or even increased the length of the epidermal cells in some locations in the growth zone compared to the control treatment, the final length of the epidermal cells was reduced by 14% at 120 mmol/L NaCl. Thus, we concluded that the observed reduction in the leaf elongation rate derived in part from the reduced cell division rate and either the shortened cell elongation zone or shortened duration of cell elongation. This suggests that more attention should be paid to the effects of salinity on those properties of cell production and the period of cell maturation that are related to the properties of cell wall. [ABSTRACT FROM AUTHOR]

• Background and Aims Cassava (Manihot esculenta) is an important food crop in the tropics that has a high growth rate in optimal conditions, but also performs well in drought-prone climates. The objectives of this work were to determine the effects of water deficit and rewatering on the rate of expansion of leaves at different developmental stages and to evaluate the extent to which decreases in cell proliferation, expansion, and delay in development are responsible for reduced growth.• Methods Glasshouse-grown cassava plants were subjected to 8 d of water deficit followed by rewatering. Leaves at 15 developmental stages from nearly full size to meristematic were sampled, and epidermal cell size and number were measured on leaves at four developmental stages.• Key Results Leaf expansion and development were nearly halted during stress but resumed vigorously after rewatering. In advanced-stage leaves (Group 1) in which development was solely by cell expansion, expansion resumed after rewatering, but not sufficiently for cell size to equal that of controls at maturity. In Group 2 (cell proliferation), relative expansion rate and cell proliferation were delayed until rewatering, but then recovered partially, so that loss of leaf area was due to decreased cell numbers per leaf. In Group 3 (early meristematic development) final leaf area was not affected by stress, but development was delayed by 4–6 d. On a plant basis, the proportion of loss of leaf area over 26 d attributed to leaves at each developmental stage was 29, 50 and 21 % in Group 1, 2 and 3, respectively.• Conclusions Although cell growth processes were sensitive to mild water deficit, they recovered to a large extent, and much of the reduction in leaf area was caused by developmental delay and a reduction in cell division in the youngest, meristematic leaves. [ABSTRACT FROM AUTHOR]

Summary • To assess the influence of mechanical impedance on cell fluxes in the root cap, maize (Zea mays ) seedlings were grown in either loose or compacted sand with penetration resistances of 0.2 MPa and 3.8 MPa, respectively. Numbers of cap cells were estimated using image analysis, and cell doubling times using the colchicine technique. • There were 5930 cells in the caps in the compact and 6900 cells in the loose control after 24 h growth in sand. Cell production rates were 2010 cells d[sup -1] in compact and 1570 cells d[sup -1] in loose sand. • These numbers represent accumulations of 4960 and 3540 detached cells d[sup -1] around the cap periphery following the two types of treatment. The total number of detached cells was estimated as sufficient to completely cover the whole root cap in the compact sand, but only 11% of the root cap in the loose sand. • In conclusion, mechanical impedance slightly enhanced meristematic activities in the lateral region of the root cap. The release of extra border cells would aid root penetration into the compact sand. [ABSTRACT FROM AUTHOR]

Battery cell production is a complex process chain with interlinked manufacturing processes. Calendering in particular has an enormous influence on the subsequent manufacturing steps and final cell performance. However, the effects on the mechanical properties of the electrode, in particular, have been insufficiently investigated. For this reason, the impact of different densification rates during calendering on the electrochemical cell performance of NMC811 (LiNi0.8Mn0.1Co0.1O2) half-cells are investigated to identify the relevant calendering parameters. Based on this investigation, an experimental design has been derived. Electrode elongations after calendering in and orthogonal to the running direction of the NMC811 cathode are investigated in comparison with a hard carbon anode after calendering. Elongations orthogonal to the machine direction are observed to have no major dependencies on the compaction rate during calendering. In the machine direction, however, significant elongation occurs as a dependency of the compaction rate for both the hard carbon anode and the NMC811. In addition, the geometric shape of the NMC811 electrodes after separation into individual sheets is investigated with regard to different compaction rates during calendering. It is shown that the corrugations that occur during calendering are propagated into the single electrode, depending on the compaction rate. [ABSTRACT FROM AUTHOR]

Li-ion cells of the industrially-relevant 21700 format were built on pilot-scale with tabs made from (a) the electrodes' current collecting foils (Al and Cu, "foil tabs") in comparison with (b) conventional tabs (Al and Ni) welded to the electrodes' current collecting foils ("welded tabs"). Both cell types use the same anode (graphite), cathode (NMC622), separator, electrolyte, as well as the same tab positions. This allows a direct comparison of welded tabs and foil tabs regarding formation, C-rate capability, cell electrical resistance, and long-term cycling stability tests. Our data reproducibly shows 14.4% longer cycling stability and 11.2% increased total charge throughput in the case of the cells with foil tabs until 80% SOH, which is likely due to less inhomogeneities in the case of the foil tab design. [ABSTRACT FROM AUTHOR]

More than 60% of tree phytomass is concentrated in stem wood, which is the result of periodic activity of the cambium. Nevertheless, there are few attempts to quantitatively describe cambium dynamics. In this study, we develop a state-of-the-art band model of cambium development, based on the kinetic heterogeneity of the cambial zone and the connectivity of the cell structure. The model describes seasonal cambium development based on an exponential function under climate forcing which can be effectively used to estimate the seasonal cell production for individual trees. It was shown that the model is able to simulate different cell production for fast-, middle- and slow-growing trees under the same climate forcing. Based on actual measurements of cell production for two contrasted trees, the model effectively reconstructed long-term cell production variability (up to 75% of explained variance) of both tree-ring characteristics over the period 1937−2012. The new model significantly simplifies the assessment of seasonal cell production for individual trees of a studied forest stand and allows the entire range of individual absolute variability in the ring formation of any tree in the stand to be quantified, which can lead to a better understanding of the anatomy of xylem formation, a key component of the carbon cycle. [ABSTRACT FROM AUTHOR]

Rates of mitosis in each of the four tiers of the cap meristem of primary roots of Zea mays L. were measured at uniform root length by a stathmokinetic method and compared with rates for other regions of the apices in seedlings growing at between 15 and 35°C. The highest elemental rate of cap cell production in the proximal tier and in the cap meristem as a whole occurs at 26°C and the proportion of cells supplied by the proximal tier rises from 48% at 15°C to 90% at 35°C. The number of cells in the whole cap and in its meristem decreases with increasing temperature. This is due to the general reduction in the width of root apices with age and growth in length being faster at the higher temperatures. The slimming of the apex is effected by a decline in the proportion of divisions that are longitudinal to the files of cells at the quiescent centre. This is enhanced by a slight but continuous increase in the rate of mitosis in the quiescent centre the higher the temperature (in contrast with the rest of the root whose maximal rate is at 28°C). The decline results in an increase in the elemental rate for longitudinal divisions in the cap initials from 0.02 to 0.17 cells per cell per day between 15 and 35°C and a consequent chant4e in the cell pattern in the cap. [ABSTRACT FROM AUTHOR]

Laboratory automation is a key driver in biotechnology and an enabler for powerful new technologies and applications. In particular, in the field of personalized therapies, automation in research and production is a prerequisite for achieving cost efficiency and broad availability of tailored treatments. For this reason, we present the StemCellDiscovery, a fully automated robotic laboratory for the cultivation of human mesenchymal stem cells (hMSCs) in small scale and in parallel. While the system can handle different kinds of adherent cells, here, we focus on the cultivation of adipose-derived hMSCs. The StemCellDiscovery provides an in-line visual quality control for automated confluence estimation, which is realized by combining high-speed microscopy with deep learning-based image processing. We demonstrate the feasibility of the algorithm to detect hMSCs in culture at different densities and calculate confluences based on the resulting image. Furthermore, we show that the StemCellDiscovery is capable of expanding adipose-derived hMSCs in a fully automated manner using the confluence estimation algorithm. In order to estimate the system capacity under high-throughput conditions, we modeled the production environment in a simulation software. The simulations of the production process indicate that the robotic laboratory is capable of handling more than 95 cell culture plates per day. [ABSTRACT FROM AUTHOR]

While human induced pluripotent stem cells (hiPSCs) provide novel prospects for disease-modeling, the high phenotypic variability seen across different lines demands usage of large hiPSC cohorts to decipher the impact of individual genetic variants. Thus, a much higher grade of parallelization, and throughput in the production of hiPSCs is needed, which can only be achieved by implementing automated solutions for cell reprogramming, and hiPSC expansion. Here, we describe the StemCellFactory, an automated, modular platform covering the entire process of hiPSC production, ranging from adult human fibroblast expansion, Sendai virus-based reprogramming to automated isolation, and parallel expansion of hiPSC clones. We have developed a feeder-free, Sendai virus-mediated reprogramming protocol suitable for cell culture processing via a robotic liquid handling unit that delivers footprint-free hiPSCs within 3 weeks with state-of-the-art efficiencies. Evolving hiPSC colonies are automatically detected, harvested, and clonally propagated in 24-well plates. In order to ensure high fidelity performance, we have implemented a high-speed microscope for in-process quality control, and image-based confluence measurements for automated dilution ratio calculation. This confluence-based splitting approach enables parallel, and individual expansion of hiPSCs in 24-well plates or scale-up in 6-well plates across at least 10 passages. Automatically expanded hiPSCs exhibit normal growth characteristics, and show sustained expression of the pluripotency associated stem cell marker TRA-1-60 over at least 5 weeks (10 passages). Our set-up enables automated, user-independent expansion of hiPSCs under fully defined conditions, and could be exploited to generate a large number of hiPSC lines for disease modeling, and drug screening at industrial scale, and quality., (Copyright © 2020 Elanzew, Nießing, Langendoerfer, Rippel, Piotrowski, Schenk, Kulik, Peitz, Breitkreuz, Jung, Wanek, Stappert, Schmitt, Haupt, Zenke, König and Brüstle.)

Human cardiomyocytes (CMs) have potential for use in therapeutic cell therapy and high-throughput drug screening. Because of the inability to expand adult CMs, their large-scale production from human pluripotent stem cells (hPSC) has been suggested. Significant improvements have been made in understanding directed differentiation processes of CMs from hPSCs and their suspension culture-based production at chemically defined conditions. However, optimization experiments are costly, time-consuming, and highly variable, leading to challenges in developing reliable and consistent protocols for the generation of large CM numbers at high purity. This study examined the ability of data-driven modeling with machine learning for identifying key experimental conditions and predicting final CM content using data collected during hPSC-cardiac differentiation in advanced stirred tank bioreactors (STBRs). Through feature selection, we identified process conditions, features, and patterns that are the most influential on and predictive of the CM content at the process endpoint, on differentiation day 10 (dd10). Process-related features were extracted from experimental data collected from 58 differentiation experiments by feature engineering. These features included data continuously collected online by the bioreactor system, such as dissolved oxygen concentration and pH patterns, as well as offline determined data, including the cell density, cell aggregate size, and nutrient concentrations. The selected features were used as inputs to construct models to classify the resulting CM content as being " sufficient " or " insufficient " regarding pre-defined thresholds. The models built using random forests and Gaussian process modeling predicted insufficient CM content for a differentiation process with 90% accuracy and precision on dd7 of the protocol and with 85% accuracy and 82% precision at a substantially earlier stage: dd5. These models provide insight into potential key factors affecting hPSC cardiac differentiation to aid in selecting future experimental conditions and can predict the final CM content at earlier process timepoints, providing cost and time savings. This study suggests that data-driven models and machine learning techniques can be employed using existing data for understanding and improving production of a specific cell type, which is potentially applicable to other lineages and critical for realization of their therapeutic applications., (Copyright © 2020 Williams, Löbel, Finklea, Halloin, Ritzenhoff, Manstein, Mohammadi, Hashemi, Zweigerdt, Lipke and Cremaschi.)