Large-scale Expansion Research Articles

An electricity-carbon joint market optimization model for coal-fired power system under China's “dual-carbon” target

In the process of low-carbon transformation of power system in China, providing enough flexible service from coal-fired power units (CFPUs) is one of the most crucial answers to reduce or even avoid the operation risk which is caused by large-scale expansion of variable renewable energy (VRE). To spur CFPUs release flexibility, this paper suggests a two-stage optimal model, taking into account various peaking compensation mechanisms (VPCM) in a day-ahead power and carbon emissions trade (CET) joint market. Pre-clearing is the first stage, which maximizes social welfare, and formal clearing is the second stage, which maximizes the profit of the coal-fired power system. In contrast to the existing fixed peaking compensation mechanism (FPCM), the variable and fixed costs associated with providing peaking regulation are calculated by the VPCM. In addition, the work considers the CET market as an external carbon emissions constraint and internal constraint and no constraint are set to study the effectiveness of the current CET market. The result indicates that the VPCM can adapt more successfully to the cost of CFPUs when providing peaking regulation and increase the profit of the coal-fired power system. Then, “VPCM + external carbon constraint” enables larger profits for coal-fired power systems, whereas “FPCM + internal carbon constraint” stimulates VRE integration and reduces carbon emissions. Finally, the current CET market mechanism is insufficient to support coal-fired power plants in reducing carbon emissions as VRE rises.

P06.04.B NEW APPROACHES FOR EXPANDING GLIOBLASTOMA INFILTRATING LYMPHOCYTES

Abstract BACKGROUND Adoptive cell therapy using tumor infiltrating lymphocytes (TILs) has shown promise in melanoma and Non-Small Cell Lung Cancer. TILs culture and expansion from GBM remains challenging due to paucity of infiltrated T-cells that are also exhausted. This hinders creation of potent TILs. We have developed a new efficient method to manufacture potent TILs from GBM samples. METHODS We have developed efficient TILs manufacturing methods using both solid and aspirated liquid samples collected during vacuum assisted excision containing tumor fragments that may stem predominantly from the tumor margins and provide a source for TILs. We followed the traditional two steps: initial expansion (preREP) where T-cells are expanded with tumor cells to selectively expand tumor antigen-reactive TILs, followed by a large-scale expansion (REP) after further activation. For both steps we optimized media and reagents. RESULTS TILs cultures from solid tumors were established from enzymatically digested tissue and by fragment plating. Successful TILs yield from liquid samples required enzymatic digestion, debris removal and RBC lysis prior to culture initiation. PreREP TILs yields ranged from a few million to 2 billion viable cells for solid and liquid samples. REP of TILs from liquid samples expanded similarly from solid samples. REP of TILs reached up to 556-fold expansion (mean: 346, range: 95-556) providing promising numbers of activated TILs. The potency of the TILs was demonstrated with tumor specific Interferon-gamma production when cultured with matched tumor digest or neurospheres. CONCLUSIONS We successfully expanded TILs that are rich in cytotoxic T-cells, demonstrated their tumor reactivity and further expanded the preREP TILs to reach therapeutic doses. We have characterized the TILs by scRNA and TCRseq and analyze paired TCR reads using scRNA sequencing. Overrepresented TCR alpha and beta chains will be linked by a P2A site and will be cloned into a lentiviral vector to establish a TCR library which will be transduced into novel Jurkat Triple Parameter Reporter Cell Lines under the control of different T cell activation programs. TCR Jurkat Libraries will be cocultured with original tumor material and sorted to identify tumor reactive TCRs; enabling us to define the percentage of TCRs that are enriched by TIL isolation that are specifically reactive to tumor vs bystander expanded TCR cells. Ultimately, we aim to bring this therapy to patients in a clinical trial.

The effect of serum origin on cytokines induced killer cell expansion and function

BackgroundCytokine-induced killer (CIK) cells have shown promising results in adoptive immunotherapy. However, serum may play a determining role in the large-scale expansion of these cells for clinical applications. According to Good Manufacturing Practice (GMP) guidelines to reduce the use of animal products in cell-based therapies; therefore, this study sought to investigate the impact of serum origin and the reduced serum concentration on the pattern of cell expansion and function.MethodsPeripheral blood mononuclear cells (PBMCs) isolated from a healthy donor were expanded based on the CIK cell expansion protocol. The cell culture medium was supplemented with three types of sera comprising fetal bovine serum (FBS), human serum (HS), or human-derived platelet lysate (hPL) at different concentrations (10%, 5%, and 2.5%). The proliferation kinetics for each group were investigated for 30 days of cell culture.ResultsCell proliferation in 10% concentration of all sera (hPL, FBS, HS) was higher than their lower concentrations. Moreover, hPL was significantly associated with higher expansion rates than FBS and HS in all three concentrations. Furthermore, cells cultured in hPL showed higher viability, cytotoxicity effect, and CIK CD markers expression.ConclusionhPL at a concentration of 10% showed the best effect on CIK cell proliferation and function.

Theoretical aspects of the use of hydrogen in the diesel engine

The promotion of fuels with low carbon content is the solution to reduce pollutant emissions in all areas of transport in a relatively short time. In this context, hydrogen is privileged, being a viable alternative fuel for internal combustion engines in all fields of transport, having the advantage of preserving the basic structure of the engine. The main obstacles to the large-scale expansion of the use of hydrogen as a fuel in internal combustion engines in transport are determined by the cost of production, storage on board the vehicle and the distribution network, large investments being required. The concept of using hydrogen as an alternative fuel to the diesel engine is relatively recent, the concerns of specialists being more intense in the last two decades. The improvement of the energy and pollution performance of the diesel engine when operating in a dual system, with diesel and hydrogen, is determined by the improvement of the combustion process due to the good combustion properties of hydrogen. The paper presents theoretical modeling results regarding the influence of hydrogen on the combustion pressure, the pressure rise rate, the heat release rate, the indicated efficiency and the nitrogen oxides emission level.

Alginate Beads as a Promising Tool for Successful Production of Viable and Pluripotent Human-Induced Pluripotent Stem Cells in a 3D Culture System.

Two-dimensional (2D)-based cell culture systems, limited by their inherent heterogeneity and scalability, are a bottleneck in the production of high-quality cells for downstream biomedical applications. Finding the optimal conditions for large-scale stem cell culture while maintaining good cellular status is challenging. The aim of this study was to assess the effects of three-dimensional (3D) culture on the viability, proliferation, self-renewal, and differentiation of human induced pluripotent stem cells (IPSCs). Various culture conditions were evaluated to determine the optimal conditions to maintain the viability and proliferation of human IPSCs in a 3D environment: static versus dynamic culture, type of adhesion protein added to alginate (Matrigel™ versus gelatin), and the addition of Y-27632t on long-term 3D culture. The proliferation ability of the cells was evaluated via the MTS proliferation assay; the expression levels of the pluripotency markers Nanog and Oct3/4, PAX6 as an ectoderm marker, and laminin-5 and fibronectin as markers of extracellular matrix synthesis were assessed; and HIF1α and HIF2α levels were measured using quantitative reverse transcription polymerase chain reaction. Using a high-aspect-ratio vessel bioreactor with a gentle, low-sheer, and low-turbulence environment with sufficient oxygenation and effective mass transfer of nutrients and waste, we verified its ability to promote cell proliferation and self-renewal. The findings showed that human IPSCs have the ability to maintain pluripotency in a feeder-free system and by inhibiting ROCK signaling and using hypoxia to improve single-cell viability in 3D culture. Furthermore, these cells demonstrated increased self-renewal and proliferation when inoculated as single cells in 3D alginate beads by adding RI during the culture period. Dynamic 3D culture is desirable for the large-scale expansion of undifferentiated human IPSCs.

The use of modern digital devices for fixing the parameters of movement of agricultural units

Despite a significant range of methods for determining mechanical failures known in modern industries, the issue of large-scale use and expansion of the scope of modern digital devices and instrumentation systems, which previously had rather limited specifics in the form of individual elements of control systems, remains relevant as before. Taking into account that in the modern state of technology, high-tech digital solutions are most in demand, capable of carrying out in-place research and fixing the operating parameters of complex systems and units used in the agro-industrial complex at a qualitative level and with a minimum time spent on diagnostic work or testing, it seems to be the most promising the use of digital inclinometers, with their low cost, manufacturability and availability, providing significant opportunities for measuring and fixing the design and technological parameters of a complex, machine or unit. The article substantiates the use of a high-precision inclinometric complex both for carrying out diagnostic work and for measuring the necessary parameters of a technological complex in motion and presents the results of experimental studies.

Characterization of Proliferation Medium and Its Effect on Differentiation of Muscle Satellite Cells from Larimichthys crocea in Cultured Fish Meat Production

To find a suitable medium for muscle satellite cells of Larimichthys crocea, herein, the effect of different basal media and coating materials on the proliferation of piscine satellite cells (PSCs) was explored. Firstly, two basal media, namely F10 and DMEM/F12, were selected as experimental materials, and high-sugar DMEM was the main basal culture medium used with fish muscle cells as a control. The results showed that the PSCs proliferated better in F10 than in DMEM/F12 or DMEM. Secondly, the effects of rat tail collagen, polylysine and matrix coatings, as compared with no coating, on the proliferation and later differentiation of PSCs were also investigated. Our results indicated that there was no significant difference between coating and no coating on the proliferation of PSCs in the F10-based medium. Meanwhile, it was found that the myotubes were washed out, and only those under matrix-coated conditions remained intact in the process of differentiation. The results also suggested that PSCs could still differentiate into myotubes without their stemness being affected after proliferation in the F10-based medium. Hence, this study identified an efficient proliferation medium based on F10 basal medium that could shorten the culture time and maintain the stemness of PSCs, thus providing a basis for large-scale cell expansion and cell-culture-based meat production in the future.

ANOTHER LOOK AT A SENSIBLE FISCAL POLICY FOR THE SHARP RISE IN GOVERNMENT DEBT

Abstract This paper weighs possible medium-term responsible policy choices to the extraordinary expansion of government spending in response to the COVID-19 outbreak. The paper is divided into two parts. In part 1 of the paper, we look at conventional debt sustainability and question whether conventional rules created during a period of high interest rates and high inflation remain relevant. Current and future conditions support a case for government debt/GDP to remain elevated compared to history, conditional upon limited state interference in the economy to allow appropriate allocation of capital and resources. In part 2, we consider the historical experience of the United Kingdom. History shows the country had several examples of rapid, large-scale expansion of government debt relative to the size of the economy. On each occasion, the elevated level of debt-to-GDP was later reduced by a combination of relatively benign factors, including commitment to low inflation and sound monetary system. This supported the financial probity of the UK government and allowed it to continue to borrow unimpeded.

Comparison of Cost and Potency of Human Mesenchymal Stromal Cell Conditioned Medium Derived from 2- and 3-Dimensional Cultures.

Mesenchymal stromal cell (MSC)-derived products, such as trophic factors (MTFs), have anti-inflammatory properties that make them attractive for cell-free treatment. Three-dimensional (3D) culture can enhance these properties, and large-scale expansion using a bioreactor can reduce manufacturing costs. Three lots of MTFs were obtained from umbilical cord MSCs produced by either monolayer culture (Monol MTF) or using a 3D microcarrier in a spinner flask dynamic system (Bioreactor MTF). The resulting MTFs were tested and compared using anti-inflammatory potency assays in two different systems: (1) a phytohemagglutinin-activated peripheral blood mononuclear cell (PBMNC) system and (2) a lipopolysaccharide (LPS)-activated macrophage system. Cytokine expression by macrophages was measured via RT-PCR. The production costs of hypothetical units of anti-inflammatory effects were calculated using the percentage of TNF-α inhibition by MTF exposure. Bioreactor MTFs had a higher inhibitory effect on TNF (p < 0.01) than monolayer MTFs (p < 0.05). The anti-inflammatory effect of Bioreactor MTFs on IL-1β, TNF-α, IL-8, IL-6, and MIP-1 was significantly higher than that of monolayer MTFs. The production cost of 1% inhibition of TNF-α was 11-40% higher using monolayer culture compared to bioreactor-derived MTFs. A 3D dynamic culture was, therefore, able to produce high-quality MTFs, with robust anti-inflammatory properties, more efficiently than monolayer static systems.

School resources, peer inputs, and student outcomes in adult education

This paper studies a large-scale educational expansion to assess whether shocks to educational inputs affect the academic achievement of adult education students. I analyze the effects of a Swedish program that rapidly doubled enrollment in adult education, thus straining school resources. The program targeted low-educated, unemployed adults aged 25 and older. Therefore, my analysis focuses on students under age 25 to reduce the risk that changes in the characteristics of the study sample drive my findings. First, I show that students in regions subject to stronger enrollment expansions experienced stronger negative shocks to educational inputs, including teacher credentials, per-pupil expenditure, and peer quality. Second, I show that the stronger negative shocks to these inputs coincided with larger increases in course dropout. Taken together, the two sets of results suggest a causal link between educational inputs and students’ academic progress in adult education.

Recent Progress on Pharmaceutical Properties of Extracellular Vesicles from Mesenchymal Stem Cells--Review

Mesenchymal stem cells (MSCs) have been officially approved in many countries to treat graft-versus-host disease, autoimmune disorders and those associated with tissue regeneration after hematopoietic stem cell transplantation. Studies in recent years have confirmed that MSC acts mainly through paracrine mechanism, in which extracellular vesicles secreted by MSC (MSC-EV) play a central role. MSC-EV has overwhelming advantages over MSC itself in the setting of adverse effects in clinical application, indicating that MSC-EV might take the place of its parent cells to be a potentially therapeutic tool for "cell-free therapy". The pharmaceutical properties of MSC-EV largely depend upon the practical and optimal techniques including large-scale expansion of MSC, the modification of MSC based on the indications and the in vivo dynamic features of MSC-EV, and the methods for preparing and harvesting large amounts of MSC-EV. The recent progresses on the issues above will be briefly reviewed.

Deacetylation of FOXP1 by HDAC7 potentiates self-renewal of mesenchymal stem cells

BackgroundMesenchymal stem cells (MSCs) are widely used in a variety of tissue regeneration and clinical trials due to their multiple differentiation potency. However, it remains challenging to maintain their replicative capability during in vitro passaging while preventing their premature cellular senescence. Forkhead Box P1 (FOXP1), a FOX family transcription factor, has been revealed to regulate MSC cell fate commitment and self-renewal capacity in our previous study.MethodsMass spectra analysis was performed to identify acetylation sites in FOXP1 protein. Single and double knockout mice of FOXP1 and HDAC7 were generated and analyzed with bone marrow MSCs properties. Gene engineering in human embryonic stem cell (hESC)-derived MSCs was obtained to evaluate the impact of FOXP1 key modification on MSC self-renewal potency.ResultsFOXP1 is deacetylated and potentiated by histone deacetylase 7 (HDAC7) in MSCs. FOXP1 and HDAC7 cooperatively sustain bone marrow MSC self-renewal potency while attenuating their cellular senescence. A mutation within human FOXP1 at acetylation site (T176G) homologous to murine FOXP1 T172G profoundly augmented MSC expansion capacity during early passages.ConclusionThese findings reveal a heretofore unanticipated mechanism by which deacetylation of FOXP1 potentiates self-renewal of MSC and protects them from cellular senescence. Acetylation of FOXP1 residue T172 as a critical modification underlying MSC proliferative capacity. We suggest that in vivo gene editing of FOXP1 may provide a novel avenue for manipulating MSC capability during large-scale expansion in clinical trials.

Analysis and modification of central carbon metabolism in Hypsizygus marmoreus for improving mycelial growth performance and fruiting body yield.

Hypsizygus marmoreus is one of the main industrially cultivated varieties of edible fungi, with a delicious taste and high nutritional value. However, the long harvest period of 130-150 days greatly limits its large-scale expansion. This study aimed to investigate the effects of central carbon metabolism (CCM) on the mycelial growth performance and fruiting body formation of H. marmoreus. Nine edible fungi with different harvest periods were collected and used to evaluate their intracellular carbon metabolic differences in the CCM, which revealed that the imbalanced distribution of intracellular carbon metabolic levels in the CCM of H. marmoreus might be one of the key factors resulting in a slow mycelial growth rate and a long harvest period. Further analysis by three strategies, including metabolomics, adaptation of different carbon sources, and chemical interference, confirmed that low carbon flux into the pentose phosphate pathway (PPP) limited the supply of raw materials, reduced power, and thus influenced the mycelial growth of H. marmoreus. Furthermore, four transformants with increased expression levels of glucose-6-phosphate dehydrogenase (G6PDH), a key rate-limiting enzyme in the PPP of H. marmoreus, were developed and showed more extracellular soluble protein secretion and higher sugar assimilation rates, as well as improved mycelial growth rates in bottle substrate mixtures. Finally, cultivation experiments indicated that the maturation periods of the fruiting body with ~4-5 days in advance and the maximum fruiting body yield of 574.8 g per bag with an increase of 7.4% were achieved by improving the G6PDH expression level of the PPP in H. marmoreus. This study showed that CCM played an important role in the mycelial growth and development of H. marmoreus, which provided new insights for future advancements in cultivating and breeding edible fungi.

Large-Scale Whole Genome Sequence Analysis of >22,000 Subjects Provides no Evidence of FMR1 Premutation Allele Involvement in Autism Spectrum Disorder.

Expansion of a CGG repeat in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene on the X chromosome is the cause of Fragile X Syndrome (FXS). The repeat length of unaffected individuals varies between 5-40 repeats, whereas >200 repeats are observed in cases of FXS. The intermediate range between 55-200 repeats is considered the premutation range and is observed in roughly 1:300 females and 1:900 males in the general population. With the availability of large-scale whole genome sequence (WGS) data and the development of computational tools to detect repeat expansions, we systematically examined the role of FMR1 premutation alleles in autism spectrum disorder (ASD) susceptibility, assess the prevalence, and consider the allelic stability between parents and offspring. We analyzed the WGS data of 22,053 subjects, including 32 FXS positive controls, 1359 population controls, and 5467 ASD families. We observed no FMR1 full mutation range repeats among the ASD parent-offspring families but identified 180 family members with premutation range alleles, which represents a higher prevalence compared to the independent WGS control sample and previous reports in the literature. A sex-specific analysis between probands and unaffected siblings did not reveal a significant increase in the burden of premutation alleles in either males or females with ASD. PCR validation, however, suggests an overestimation of the frequency of FMR1 premutation range alleles through computational analysis of WGS data. Overall, we show the utility of large-scale repeat expansion screening in WGS data and conclude that there is no apparent evidence of FMR1 premutation alleles contributing to ASD susceptibility.

Fine-grained access control policy in blockchain-enabled edge computing

In the process of data sharing and interaction between untrusted intelligence edge devices, there are risks of misuse and tampering with the data. Hence, how to ensure data security and prevent unauthorized data access is the key problem to be solved in the cloud edge collaborative architecture. However, due to the heterogeneity of edge devices and the diversity of data sources, traditional access control methods cannot meet the requirements of the large-scale, distributed, dynamic and flexible expansion of edge intelligence applications. Therefore, this paper studies the fine-grained data access control method on the basis of smart contracts, and implements the attribute-based access control (ABAC) model through smart contracts. To improve the query efficiency of attributes and policies in the process of access request decision, an attribute management scheme is designed on the basis of the Bloom filter to achieve fast retrieval of attributes and policies. The decentralized fine-grained access control method is tested under the performance indicators such as retrieval delay, deployment delay, rule reduction rate and decision response time.

Serving the Underserved: Microcredit as a Pathway to Commercial Banks

Abstract A large-scale microcredit expansion program—together with a credit bureau accessible to all lenders—can enable unbanked borrowers to build a credit history, facilitating their transition to commercial banks. Loan-level data from Rwanda show the program improved access to credit and reduced poverty. A sizable share of first-time borrowers switched to commercial banks, which cream-skim less risky borrowers and grant them larger, cheaper, and longer-maturity loans. Switchers have lower default risk than nonswitchers and are not riskier than other bank borrowers. Switchers also obtain better loan terms from banks compared with first-time bank borrowers without a credit history.

Large-Scale Cell Production Based on GMP-Grade Dissolvable Porous Microcarriers.

Researchers in the cell and gene therapy (CGT) industry have long faced a formidable challenge in the efficient and large-scale expansion of cells. To address the primary shortcomings of the two-dimensional (2D) planar culturing system, we innovatively developed an automated closed industrial scale cell production (ACISCP) platform based on a GMP-grade, dissolvable, and porous microcarrier for the 3D culture of adherent cells, including human mesenchymal stem/stromal cells (hMSCs), HEK293T cells, and Vero cells. To achieve large-scale expansion, a two-stage expansion was conducted with 5 L and 15 L stirred-tank bioreactors to yield 1.1 x 1010 hMSCs with an overall 128-fold expansion within 9 days. The cells were harvested by completely dissolving the microcarriers, concentrated, washed and formulated with a continuous-flow centrifuge-based cell processing system, and then aliquoted with a cell filling system. Compared with 2D planar culture, there are no significant differences in the quality of hMSCs harvested from 3D culture. We have also applied these dissolvable porous microcarriers to other popular cell types in the CGT sector; specifically, HEK293T cells and Vero cells have been cultivated to peak cell densities of 1.68 x 107 cells/mL and 1.08 x 107 cells/mL, respectively. This study provides a protocol for using a bioprocess engineering platform harnessing the characteristics of GMP-grade dissolvable microcarriers and advanced closed equipment to achieve the industrial-scale manufacturing of adherent cells.

Risk aversion and flexibility options in electricity markets

Flexibility options, such as demand response, energy storage and interconnection, have the potential to reduce variation in electricity prices between different future scenarios, thereby reducing investment risk. Investing in flexibility options can also lower the need for generation capacity. However, there are complex interactions between different flexibility options. In this paper, we investigate the interactions between flexibility and investment risk in electricity markets. In particular, we focus on the investment strategies of risk-averse decision-makers. We employ a large-scale stochastic transmission and generation expansion model of the European electricity system, providing it with uncertain future scenarios based on ENTSOs’ Ten-Year Network Development Plan. Using this model, we first investigate the effect of risk aversion on investment decisions. We find that the interplay of parameters leads to (i) more investment in a less emission-intensive energy system if planners are risk averse (hedging against CO2 price uncertainty), (ii) constant total installed capacity, regardless of the level of risk aversion (i.e. planners do not hedge against demand and uncertainties when deploying renewable energy sources) and (iii) an allocation of investments that disregards cost differences for load shedding across Europe. Second, we examine the individual effects of three flexibility elements on optimal investment levels at different levels of risk aversion: demand response, investment in additional interconnection capacity and investment in additional energy storage. We show that flexible technologies have a higher value for risk-averse decision-makers, although the effects are nonlinear. Finally, we investigate the interactions between the flexibility elements. We find that risk-averse decision-makers show a strong preference for transmission-grid expansion once flexibility is available at a low cost.

Mesenchymal stem cells paracrine proteins from three-dimensional dynamic culture system promoted wound healing in third-degree burn models.

Recovery of skin function remains a significant clinical challenge for deep burns owing to the severe scar formation and poor appendage regeneration, and stem cell therapy has shown great potential for injured tissue regeneration. Here, a cell-free therapy system for deep burn skin was explored using mesenchymal stem cell paracrine proteins (MSC-PP) and polyethylene glycol (PEG) temperature-sensitive hydrogels. A three-dimensional (3D) dynamic culture system for MSCs' large-scale expansion was established using a porous gelatin microcarrier crosslinked with hyaluronic acid (PGM-HA), and the purified MSC-PP from culture supernatant was characterized by mass spectrometric analysis. The results showed the 3D dynamic culture system regulated MSCs cell cycle, reduced apoptosis, and decreased lactic acid content, and the MSC-PP produced in 3D group can promote cell proliferation, migration, and adhesion. The MSC-PP + PEG system maintained stable release in 28 days of observation in vitro. The in vivo therapeutic efficacy was investigated in the rabbit's third-degree burn model, and saline, PEG, MSC-PP, and MSC-PP + PEG treatments groups were set. The in vivo results showed that the MSC-PP + PEG group significantly improved wound healing, inhibited scar formation, and facilitated skin appendage regeneration. In conclusion, the MSC-PP + PEG sustained-release system provides a potentially effective treatment for deep burn skin healing.

Spatiotemporal dynamics of water supply–demand patterns under large-scale paddy expansion: Implications for regional sustainable water resource management

Spatiotemporal dynamics of water supply–demand patterns under large-scale paddy expansion: Implications for regional sustainable water resource management