Mass production

批量生产
  • 文章类型: Journal Article
    昆虫病原真菌(EPF)可以定义为有益的多功能真核微生物,在害虫管理中显示出关键的生态服务。一些物种具有与植物建立互惠关系的特殊能力。这些真菌的大规模生产对于支持负担得起的广泛商业化和全球领域应用至关重要。在主要由行业探索的大规模生产方法中,浸没式液体发酵是一种强大且通用的技术,可以形成不同类型的繁殖体,用于害虫控制中的各种应用。通过产生单细胞结构(菌丝体,小孢子,和浸没的分生孢子)或多细胞结构(菌丝体和微菌核)。不那么频繁,一些EPF可能会形成耐环境的衣原体孢子,但是这些结构几乎总是被忽视。一个持续的研究管道,包括筛选真菌菌株,媒体优化,和适当的配方技术与对这些繁殖体形成和储存稳定性所涉及的分子线索的理解相一致,对于充分发挥潜力并微调针对节肢动物害虫和疾病媒介的强大有效生物防治剂的开发。最后,我们为深层液体发酵技术补充或取代传统的固体基质发酵方法,为大量生产许多重要的EPF提供了广阔的前景。关键点:•浸没式液体发酵(SLF)允许精确控制营养和环境因素•SLF提供了可扩展的,健壮,和成本效益高的农药生产平台•加强配方,保质期,和淹没繁殖体的田间功效仍然至关重要•了解淹没繁殖体形成背后的分子机制是推进SLF技术的关键。
    Entomopathogenic fungi (EPF) can be defined as beneficial multifunctional eukaryotic microorganisms that display pivotal ecological services in pest management, with some species possessing the special ability to establish mutualistic relationships with plants. Mass production of these fungi is critical to support affordable widespread commercialization and worldwide field application. Among the mass production methods explored mainly by industry, submerged liquid fermentation is a robust and versatile technology that allows the formation of different types of propagules designated for various applications in pest control. Many hypocrealean EPF are easily culturable on artificial substrates by producing single-celled structures (hyphal bodies, blastospores, and submerged conidia) or multicellular structures (mycelium and microsclerotia). Less frequently, some EPF may form environmentally resistant chlamydospores, but these structures have almost always been overlooked. A continued research pipeline encompassing screening fungal strains, media optimization, and proper formulation techniques aligned with the understanding of molecular cues involved in the formation and storage stability of these propagules is imperative to unlock the full potential and to fine-tune the development of robust and effective biocontrol agents against arthropod pests and vectors of diseases. Finally, we envision a bright future for the submerged liquid fermentation technology to supplement or replace the traditional solid substrate fermentation method for the mass production of many important EPF. KEY POINTS: • Submerged liquid fermentation (SLF) allows precise control of nutritional and environmental factors • SLF provides a scalable, robust, and cost-effective platform for mycopesticide production • Enhancing formulation, shelf life, and field efficacy of submerged propagules remain crucial • Understanding the molecular mechanisms behind submerged propagule formation is key to advancing SLF technology.
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  • 文章类型: Journal Article
    通过化学气相沉积(CVD)在非金属衬底上直接合成石墨烯已成为针对CVD石墨烯无转移应用的前沿研究领域。然而,稳定的大规模生产具有良好的生长速率和质量的石墨烯仍然是一个巨大的挑战。在这里,石墨烯玻璃纤维织物(GGFF)是通过在非催化玻璃纤维织物上可控生长石墨烯,采用协同二元前体CVD策略来缓解生长速率和质量之间的困境。二元前体由乙炔和丙酮组成,其中具有高分解效率的乙炔进料快速石墨烯生长,而含氧丙酮用于改善层的均匀性和质量。值得注意的是,分叉引入-汇合预混合(BI-CP)系统是自构建的,用于可控地引入气体和液体前体,实现GGFF的稳定生产。GGFF具有太阳能吸收和红外发射特性,在此基础上研制了自适应双模热管理薄膜。这种薄膜可以通过自发地感知温度,在加热和冷却模式之间自动切换,实现优异的热管理性能,加热和冷却功率分别为501.2和108.6Wm-2。这些发现为石墨烯材料的大规模批量生产开启了新的战略,并激发了进一步应用的先进可能性。
    Direct synthesis of graphene on nonmetallic substrates via chemical vapor deposition (CVD) has become a frontier research realm targeting transfer-free applications of CVD graphene. However, the stable mass production of graphene with a favorable growth rate and quality remains a grand challenge. Herein, graphene glass fiber fabric (GGFF) was successfully developed through the controllable growth of graphene on non-catalytic glass fiber fabric, employing a synergistic binary-precursor CVD strategy to alleviate the dilemma between growth rate and quality. The binary precursors consisted of acetylene and acetone, where acetylene with high decomposition efficiency fed rapid graphene growth while oxygen-containing acetone was adopted for improving the layer uniformity and quality. Notably, the bifurcating introducing-confluent premixing (BI-CP) system was self-built for the controllable introduction of gas and liquid precursors, enabling the stable production of GGFF. GGFF features solar absorption and infrared emission properties, based on which the self-adaptive dual-mode thermal management film was developed. This film can automatically switch between heating and cooling modes by spontaneously perceiving the temperature, achieving excellent thermal management performances with heating and cooling power of ∼501.2 and ∼108.6 W m-2, respectively. These findings unlock a new strategy for the large-scale batch production of graphene materials and inspire advanced possibilities for further applications.
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  • 文章类型: Journal Article
    本研究旨在分离和鉴定球孢白僵菌的本地菌株,编码为Bv065,展示了其作为针对棕榈象鼻虫Dynamisborassi的生物防治剂的潜力。源自哥伦比亚西南部自然感染的D.borassi标本,该真菌经过分子鉴定,被鉴定为B.bassiana,与已知参考菌株表现出高序列相似性。生理表征显示Bv065在25至30°C的温度范围和6至9的pH范围内蓬勃发展。此外,通过代谢谱分析确定了允许菌株最佳生长的关键碳源,包括蔗糖,D-甘露糖,和γ-氨基丁酸。这些发现为可扩展性和制定方法提供了战略见解。此外,酶分析揭示了Bv065中强大的蛋白酶活性,对催化昆虫角质层降解和促进宿主渗透至关重要,从而增强了其昆虫致病的潜力。随后的评估暴露了Bv065对D.borassi的致病性,在暴露后九天内导致大量死亡,尽管对Rhynchophoruspalmarum的效果有限。这项研究强调了了解最佳生长条件和代谢偏好的重要性。研究结果表明,Bv065是新热带地区害虫综合管理策略的有希望的候选者,特别是用于控制椰子和桃树栽培中的棕榈象鼻虫侵染。未来的研究途径包括精炼大规模生产方法,制定新颖的输送系统,并进行全面的田间功效试验,以释放Bv065在促进可持续虫害管理实践中的全部潜力。总的来说,这项研究有助于对昆虫病原真菌及其在生物防治中的关键作用的知识不断增长,为传统杀虫干预措施的生态友好替代品提供细致入微的观点。
    This study aimed to isolate and characterize a native strain of Beauveria bassiana, coded as Bv065, showcasing its potential as a biological control agent targeting the palm weevil Dynamis borassi. Originating from a naturally infected D. borassi specimen collected in southwestern Colombia, the fungus underwent molecular identification and was identified as B. bassiana, exhibiting high sequence similarity with known reference strains. The physiological characterization revealed that Bv065 thrived within a temperature range of 25 to 30 °C and a pH range of 6 to 9. Moreover, the key carbon sources that allow optimal growth of the strain were identified through metabolic profiling, including sucrose, D-mannose, and γ-amino-butyric acid. These findings offer strategic insights for scalability and formulation methodologies. Additionally, enzymatic analyses unveiled robust protease activity within Bv065, crucial for catalysing insect cuticle degradation and facilitating host penetration, thus accentuating its entomopathogenic potential. Subsequent evaluations exposed Bv065\'s pathogenicity against D. borassi, causing significant mortality within nine days of exposure, albeit exhibiting limited effectiveness against Rhynchophorus palmarum. This study underscores the importance of understanding optimal growth conditions and metabolic preferences of B. bassiana strains for developing effective biopesticides. The findings suggest Bv065 as a promising candidate for integrated pest management strategies in neotropical regions, particularly for controlling palm weevil infestations in coconut and peach palm cultivation. Future research avenues include refining mass production methodologies, formulating novel delivery systems, and conducting comprehensive field efficacy trials to unlock the full potential of Bv065 in fostering sustainable pest management practices. Overall, this study contributes to the growing body of knowledge on entomopathogenic fungi and their pivotal role in biological control, offering nuanced perspectives on eco-friendly alternatives to conventional insecticidal interventions.
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  • 文章类型: Journal Article
    免疫治疗是临床上治疗肿瘤的有效方法。锰可以激活cGAS-STING信号通路并诱导抗肿瘤免疫应答。然而,其疗效受到非特异性分布和低摄取率的阻碍。在这项研究中,我们采用微流控技术来设计和开发一种创新的制备工艺,从而产生了一种新型的锰脂质纳米颗粒(LNM)。在此过程中产生的脂质锰纳米颗粒具有高锰有效载荷,出色的稳定性,大规模生产能力,和高批次重复性。LNM已经有效地证明了激活cGAS-STING信号通路的能力,诱导促炎细胞因子的产生,并抑制肿瘤的发展。值得注意的是,LNM不需要联合化疗药物或其他免疫激活剂。因此,LNM提供了一个保险箱,直截了当,和有效的抗肿瘤免疫激活策略,具有可扩展生产的潜力。
    Immunotherapy is a clinically effective method for treating tumors. Manganese can activate the cGAS-STING signaling pathway and induce an anti-tumor immune response. However, its efficacy is hindered by non-specific distribution and low uptake rates. In this study, we employed microfluidic technology to design and develop an innovative preparation process, resulting in the creation of a novel manganese lipid nanoparticle (LNM). The lipid manganese nanoparticle produced in this process boasts a high manganese payload, excellent stability, the capacity for large-scale production, and high batch repeatability. LNM has effectively demonstrated the ability to activate the cGAS-STING signaling pathway, induce the production of pro-inflammatory cytokines, and inhibit tumor development. Notably, LNM does not require combination chemotherapy drugs or other immune activators. Therefore, LNM presents a safe, straightforward, and efficient strategy for anti-tumor immune activation, with the potential for scalable production.
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  • 文章类型: Journal Article
    激光粉末床融合(LPBF)可以制造复杂的,几何复杂的结构,具有足够精细的表面光洁度,适用于许多工程应用,具有多种可用的原料金属。然而,与传统制造方法相比,LPBF系统的生产率不是很适合大规模生产。LPBF系统以每小时100克测量其沉积速率,而其他工艺以千克/小时为单位,甚至在成形等工艺的情况下,冲压,和铸造,每小时100公斤。在工业中广泛采用大规模生产,LPBF需要一种新的可扩展架构,该架构可以使沉积速率提高许多数量级,同时保持增材制造的几何自由度。本文探讨了通过应用(1)旋转工作台运动学布置,可以实现生产率提高四个数量级的概念;(2)同时工作的激光器数量惊人;(3)减少激光光学尺寸;(4)改进的扫描技术;(5)优化环形构建板尺寸。为了从理论上证明生产改进的可能性,提出了与电动汽车行业相关的同步磁阻电机的生产率分析,鉴于最近可印刷软磁合金的多样性增加。该分析提供了对优化大规模生产的旋转粉末床融合所需的架构和工艺参数的影响的见解。
    Laser powder bed fusion (LPBF) enables the fabrication of intricate, geometrically complex structures with a sufficiently fine surface finish for many engineering applications with a diversity of available feedstock metals. However, the production rate of LPBF systems is not well suited for mass production in comparison to traditional manufacturing methods. LPBF systems measure their deposition rates in 100\'s of grams per hour, while other processes measure in kilograms per hour or even in the case of processes such as forming, stamping, and casting, 100\'s of kilograms per hour. To be widely adopted in industry for mass production, LPBF requires a new scalable architecture that enables many orders of magnitude improvement in deposition rate, while maintaining the geometry freedom of additive manufacturing. This article explores concepts that could achieve as much as four orders of magnitude increase in the production rate through the application of (1) rotary table kinematic arrangements; (2) a dramatic number of simultaneously operating lasers; (3) reductions of laser optic size; (4) improved scanning techniques; and (5) an optimization of toroidal build plate size. To theoretically demonstrate the possibilities of production improvements, a productivity analysis is proposed for synchronous reluctance motors with relevance to the electric vehicle industry, given the recent increase in the diversity of printable soft magnetic alloys. The analysis provides insights into the impact of the architecture and process parameters necessary to optimize rotary powder bed fusion for mass production.
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  • 文章类型: Journal Article
    用于氧还原反应的高活性单原子电催化剂对于提高能量转化效率至关重要,但是它们的金属中心选择有限,稳定性也不令人满意。在这里,我们报告了通过调整轴向基团的d轨道杂交来优化反应中间体的结合能,从而转化了非活性亚组IVB(Ti,Zr,Hf)将部分(MN4)转化为活性基序(MN4O),正如理论计算所证实的那样。金属-配体共价和金属-中间共价之间的竞争影响金属位点和中间体之间的d-p轨道杂化,将金属中心转换为活性位点。随后,通过高能研磨和热解,在石墨烯(s-M-N/O-C)催化剂上大规模制备了由氮/氧基团配位的分散单原子M位点。令人印象深刻的是,s-Hf-N/O-C催化剂与5.08wt.%Hf表现出0.920V的半波电位,在锌空气电池中具有令人鼓舞的性能,其非凡的循环寿命超过1,600h,峰值功率密度为256.9mWcm-2。这项工作提供了有前途的单原子电催化剂和制备用于氧还原反应的其他催化剂的原理。本文受版权保护。保留所有权利。
    Highly active single-atom electrocatalysts for the oxygen reduction reaction are crucial for improving the energy conversion efficiency, but they suffer from a limited choice of metal centers and unsatisfactory stabilities. Here, this work reports that optimization of the binding energies for reaction intermediates by tuning the d-orbital hybridization with axial groups converts inactive subgroup-IVB (Ti, Zr, Hf) moieties (MN4) into active motifs (MN4O), as confirmed with theoretical calculations. The competition between metal-ligand covalency and metal-intermediate covalency affects the d-p orbital hybridization between the metal site and the intermediates, converting the metal centers into active sites. Subsequently, dispersed single-atom M sites coordinated by nitrogen/oxygen groups have been prepared on graphene (s-M-N/O-C) catalysts on a large-scale with high-energy milling and pyrolysis. Impressively, the s-Hf-N/O-C catalyst with 5.08 wt% Hf exhibits a half-wave potential of 0.920 V and encouraging performance in a zinc-air battery with an extraordinary cycling life of over 1600 h and a large peak power-density of 256.9 mW cm-2. This work provides promising single-atom electrocatalysts and principles for preparing other catalysts for the oxygen reduction reaction.
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  • 文章类型: Journal Article
    微针(MNs)技术已经在经皮药物递送中进行了20多年的研究,并进行了数百次临床试验。然而,由于材料安全方面的挑战,目前在医学上没有市售的MN,具有成本效益的制造,和大规模制造。在这里,首次提出了一种基于红外辐照工艺的水凝胶微针的快速绿色制造方法。优化配方为聚乙烯醇(PVA)和聚乙烯吡咯烷酮(PVP),作为交联材料和成孔剂,分别。制造方法包括将MNs贴片在70°C的红外辐射下放置2分钟,然后退火以获得具有优异溶胀行为的HMNs,机械强度,和生物相容性。当模型药物壬二酸(AZA)和苦参碱(MAT)加载到HMNs系统中时,MAT的化学稳定性明显提高。离体透皮给药实验表明,HMNs可以实现AZA和MAT的同步释放,两种药物的24小时经皮通透性分别为73.09±0.48%和71.56±1.23%,分别。体内药代动力学研究,HMNs给药呈现两种药物的剂量依赖性稳定的血药浓度。此外,在药效学评价中,载药HMNs组有显著的抗肿瘤疗效和生物安全性.总之,高效的,方便,基于红外辐射的低成本制造方法为大量生产载药HMN提供了可能性,显示出工业制造业发展的潜力。
    Microneedles (MNs) technology has been studied in transdermal drug delivery for more than 20 years with hundreds of clinical trials conducted. However, there are currently no commercially available MNs in medicine due to challenges in materials safety, cost-effective fabrication, and large-scale manufacturing. Herein, an approach for rapid and green fabrication of hydrogel microneedles (HMNs) based on infrared irradiation process was proposed for the first time. The optimized formulation consisted of polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP), which acted as cross-linked materials and pore-forming agents, respectively. The manufacturing method involved placing MNs patches under infrared irradiation at 70 °C for 2 min and annealing to obtain HMNs with excellent swelling behavior, mechanical strength, and biocompatibility. When model drugs azelaic acid (AZA) and matrine (MAT) were loaded into HMNs systems, the chemical stability of MAT was significantly improved. Ex vivo transdermal delivery experiments indicated that HMNs could achieve synchronous release of AZA and MAT, and the 24-hour percutaneous permeability rates of both drugs were 73.09 ± 0.48 % and 71.56 ± 1.23 %, respectively. In-vivo pharmacokinetic studies, HMNs administration presented dose-dependent stable blood drug concentrations for both drugs. Additionally, prominent anti-tumor efficacy and biosecurity were observed in the drug-loaded HMNs group in the pharmacodynamic evaluation. In summary, the efficient, convenient, and low-cost fabrication method based on infrared irradiation offers the possibility of mass production of drug-loaded HMNs, showing potential for industrial manufacturing development.
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  • 文章类型: Journal Article
    我们调查了六种昆虫病原真菌(EPF)的八种分离物的分生孢子大规模生产,Aphanocladium专辑(ARSEF1329),白僵菌(ARSEF252和3462),无光软霉菌(ARSEF6433),sensulato的绿僵菌(ARSEF2341),平山绿杆菌(ARSEF1545),在四种水分条件(75-100%)下,白米或糙米上的青霉(ARSEF6430和6651)。还评估了八种真菌分离株的大量生产的分生孢子对UV-B辐射和热(45°C)的耐受性。对于每个比较的水分含量,将聚丙烯袋中的20克大米样品用每种真菌分离物接种三次,并在28±1°C下孵育14天。然后通过洗涤底物收获分生孢子,和分生孢子浓度通过血细胞计数器计数确定。分生孢子悬浮液在PDAY上接种0.002%苯菌灵在培养皿中,并暴露于978mWm-2的Quaite加权UV-B2小时。此外,分生孢子悬浮液暴露于45°C3小时,并在PDAY上接种苯菌灵等分试样。将板在28±1°C下孵育,48小时后,以400倍放大倍数评估发芽。对于所有真菌物种,白米的分生孢子产量通常高于糙米,除无花果乳杆菌ARSEF6433外,不考虑水分组合。100%的湿度条件提供了较高的分生孢子产量。添加10%花生油可提高S.lanosonivum分离株ARSEF6430的分生孢子产量。在100%水的白米上,B.basianaARSEF3462产生最高的分生孢子产量(约1.3×1010分生孢子g-1)。在不同水分条件下,白米产生的分生孢子对UV-B辐射或热的耐受性没有差异。然而,对B.bassiana观察到对UV-B辐射和热的高耐受性,马尾藻,和A.专辑分离。经热处理的羊毛虫和无光拉迪乳杆菌的分生孢子未发芽。
    We investigated conidial mass production of eight isolates of six entomopathogenic fungi (EPF), Aphanocladium album (ARSEF 1329), Beauveria bassiana (ARSEF 252 and 3462), Lecanicillium aphanocladii (ARSEF 6433), Metarhizium anisopliae sensu lato (ARSEF 2341), Metarhizium pingshaense (ARSEF 1545), and Simplicillium lanosoniveum (ARSEF 6430 and 6651) on white or brown rice at four moisture conditions (75-100%). The tolerance of mass-produced conidia of the eight fungal isolates to UV-B radiation and heat (45 °C) were also evaluated. For each moisture content compared, a 20-g sample of rice in a polypropylene bag was inoculated with each fungal isolate in three replicates and incubated at 28 ± 1 °C for 14 days. Conidia were then harvested by washing the substrate, and conidial concentrations determined by haemocytometer counts. Conidial suspensions were inoculated on PDAY with 0.002% benomyl in Petri plates and exposed to 978 mW m-2 of Quaite-weighted UV-B for 2 h. Additionally, conidial suspensions were exposed to 45 °C for 3 h, and aliquots inoculated on PDAY with benomyl. The plates were incubated at 28 ± 1 °C, and germination was assessed at 400 × magnification after 48 h. Conidial production was generally higher on white rice than on brown rice for all fungal species, except for L. aphanocladii ARSEF 6433, regardless of moisture combinations. The 100% moisture condition provided higher conidial production for B. bassiana (ARSEF 252 and ARSEF 3462) and M. anisopliae (ARSEF 2341) isolates, while the addition of 10% peanut oil enhanced conidial yield for S. lanosoniveum isolate ARSEF 6430. B. bassiana ARSEF 3462 on white rice with 100% water yielded the highest conidial production (approximately 1.3 × 1010 conidia g-1 of substrate). Conidia produced on white rice with the different moisture conditions did not differ in tolerance to UV-B radiation or heat. However, high tolerance to UV-B radiation and heat was observed for B. bassiana, M. anisopliae, and A. album isolates. Heat-treated conidia of S. lanosoniveum and L. aphanocladii did not germinate.
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  • 文章类型: Journal Article
    高硬度,脆性,和热阻在熔融石英透镜的可扩展制造中带来了重大挑战,在许多应用中广泛使用。通过将二氧化硅纳米粉体与可光固化树脂搅拌来利用纳米复合材料,新出现的低温预成型技术为制造透明熔融石英组件提供了范式转变。然而,制备二氧化硅浆料并小心地蒸发有机物可显著增加基于纳米复合材料的技术的工艺复杂性并降低制造效率。通过在几分钟内将纯二氧化硅纳米粉末直接压在复杂形状的金属模具上,这项工作报告了一种完全不同的室温模塑方法,能够在不含有机添加剂的情况下大量复制复杂形状的二氧化硅透镜。烧结复制的镜片后,全透明熔融石英球面透镜,排成阵列,并产生具有纳米表面粗糙度和良好保留的模具形状的自由成型图案,展示了一种可扩展和具有成本效益的路线,超越了目前用于制造高质量熔融石英镜片的技术。
    The high hardness, brittleness, and thermal resistance impose significant challenges in the scalable manufacturing of fused silica lenses, which are widely used in numerous applications. Taking advantage of the nanocomposites by stirring silica nanopowders with photocurable resins, the newly emerged low-temperature pre-shaping technique provides a paradigm shift in fabricating transparent fused silica components. However, preparing the silica slurry and carefully evaporating the organics may significantly increase the process complexity and decrease the manufacturing efficiency for the nanocomposite-based technique. By directly pressing pure silica nanopowders against the complex-shaped metal molds in minutes, this work reports an entirely different room-temperature molding method capable of mass replication of complex-shaped silica lenses without organic additives. After sintering the replicated lenses, fully transparent fused silica lenses with spherical, arrayed, and freeform patterns are generated with nanometric surface roughness and well-reserved mold shapes, demonstrating a scalable and cost-effective route surpassing the current techniques for the manufacturing of high-quality fused silica lenses.
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  • 文章类型: Journal Article
    以世界卫生组织支持的南非疫苗技术转让中心为例,我们表明,将mRNA疫苗从原型转移到大规模生产所需的专有技术是mRNA疫苗进入市场的无形障碍.克服这一障碍依赖于稀缺的人力资本。鉴于这种稀缺,并为下一次大流行做准备,我们建议扩大现有世卫组织计划的范围,世卫组织学院,因此,它通过形成一个系统化的知识储备库和一个专家登记册来协调知识传播举措。正如我们所解释的,与目前的专有技术获取方法相比,这项建议在克服进入障碍方面具有优势。
    Using the South African vaccine technology transfer hub supported by the WHO as an example, we show that the know-how needed to move mRNA vaccines from prototype to mass-production acts as an invisible barrier to market entry of mRNA vaccines. Overcoming this barrier relies on scarce human capital. In view of this scarcity and in preparation for the next pandemic, we propose broadening the scope of an existing WHO program, the WHO Academy, so that it coordinates knowledge diffusion initiatives by forming a systematized repository of know-how and a register of experts. As we explain, this proposal has an advantage in overcoming barriers to entry over current approaches of know-how acquisition.
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