Formation of the stress-and-strain state of the rock mass in the roof of mined coal seam depends on the development of the mined-out space. It is believed that the coal seam is located deep enough and it can be assumed that the effect of the daylight surface on its condition can be neglected. In this case, the solution is based on the analytical approach using methods of the complex variable theory and it is reduced to the construction of a single permission analytical function. The paper reviews the evolution of the deformation processes in development of the mined-out space in presence of a hard-to-collapse elastic roof, which is capable of sinking smoothly over time, without sudden caving on the landings on the floor. A particular attention is paid to the phase when the roof and the floor touch each other, i.e. the roof caving, starting from the first touching and up to its complete caving. In this case, two sections of the hanging roof are formed, that are gradually reducing in length as the dimensions of the mined-out space increase. The area of roof caving is progressively increasing, and the vertical compressive stresses at the boundary are gradually rising, tending to reach the initial vertical pressure at the depth of the formation before the start of its mining. Tension zones relative to the horizontal and vertical stresses are identified, that are attributed to the areas of roof hang-up, which may determine the location of zones with higher methane and formation water permeability, both in the rocks between the seams and in the coal seam.
China’s management of marine ecological environments has experienced a development process that has gone from weak to strong. However, whether there are problems such as lack of systems, invalid systems, and system conflicts in the current management of marine ecological environments, and how to conduct collaborative governance among various complex subjects, remain to be answered. This paper first summarizes how China’s marine ecological environment management policy has evolved, which can be divided into five stages: the foundation stage (1949–1980), the initial establishment stage (1981–1995), the steady advancement stage (1996–2005), the deepening adjustment stage (2006–2010), and the strategic development stage (2011–present), and analyzes its characteristics at different stages. Then, this paper further explores the inherent dilemmas in the Chinese marine ecological environment management system. Finally, combined with the practical experience of marine ecological environment management in developed countries, this paper fully considers the division of responsibilities and mutual checks and balances of different subjects, flexibly configures various policy tools, and explores the mechanism of collaborative governance of marine ecological environment from the levels of government, market, the public and social organizations, so as to gradually improve the modern marine ecological environment management system and provide a reference for the government’s governance activities.
The vortex in a pump sump is a negative problem for the pump unit, which can lead to the decline of pump performance. Focusing on the internal pressure characteristics of the floor-attached vortex (FAV) and its influence on the pump unit, the FAV was analyzed adopting the previously verified numerical simulation method and experiment. The results show that the pressure in the vortex core gradually decreases with time, drops to a negative pressure at the development stage, and then reaches the lowest pressure during the continuance stage. When the negative pressure of the vortex tube is around the vaporization pressure of the continuance stage, it can cause a local cavitation at the impeller inlet. The evolution of the FAV is accompanied by a change of pressure gradient in the vortex core which is discussed in detail. This research provides theoretical guidance for a better understanding of the vortex characteristics and the optimal design for the pump.
Spectral characteristics were studied at pod development stage (75 DAS) in summer groundnut, at Pune, in western Maharashtra plain zone. A simple regression model (yield vs. vegetation index, R2= 0.94) and another multiple regression model (yield vs. B: R, G: R, NIR: R and VI, R2= 0.99) were developed to predict the yields of summer groundnut. The yield prediction model based on spectral ratios at pod development stage (75 DAS) is helpful in forecasting the yield of summer groundnut, one month in advance, in western Maharashtra plain zone.
Delivery of genome editing reagents using CRISPR-Cas ribonucleoproteins (RNPs) transfection offers several advantages over plasmid DNA-based delivery methods, including reduced off-target editing effects, mitigation of random integration of non-native DNA fragments, independence of vector constructions, and less regulatory restrictions. Compared to the use in animal systems, RNP-mediated genome editing is still at the early development stage in plants. In this study, we established an efficient and simplified protoplast-based genome editing platform for CRISPR-Cas RNP delivery, and then evaluated the efficiency, specificity, and temperature sensitivity of six Cas9 and Cas12a proteins. Our results demonstrated that Cas9 and Cas12a RNP delivery resulted in genome editing frequencies (8.7–41.2%) at various temperature conditions, 22°C, 26°C, and 37°C, with no significant temperature sensitivity. LbCas12a often exhibited the highest activities, while AsCas12a demonstrated higher sequence specificity. The high activities of CRISPR-Cas RNPs at 22° and 26°C, the temperature preferred by plant transformation and tissue culture, led to high mutagenesis efficiencies (34.0–85.2%) in the protoplast-regenerated calli and plants with the heritable mutants recovered in the next generation. This RNP delivery approach was further extended to pennycress (Thlaspi arvense), soybean (Glycine max) and Setaria viridis with up to 70.2% mutagenesis frequency. Together, this study sheds light on the choice of RNP reagents to achieve efficient transgene-free genome editing in plants.
This study evaluates the association of Biopharma company valuation with the lead drug’s development stage, orphan status, number of indications, and disease area. We also estimated annual returns Bioentrepreneurs and investors can expect from founding and investing in drug development ventures.
SDC Thomson Reuter and S&P Capital IQ were screened for majority acquisitions of US and EU Biopharma companies developing new molecular entities for prescription use (SIC code: 2834). Acquisition data were complemented with drug characteristics extracted from clinicaltrials.gov, the US Food and Drug Administration (FDA), and deal announcements. Thereafter, company valuations were combined with previously published clinical development periods alongside orphan-, indication-, and disease-specific success rates to estimate annual returns for investments in drug developing companies.
Based on a sample of 311 Biopharma acquisitions from 2005 to 2020, companies developing orphan, multi-indication, and oncology drugs were valued significantly higher than their peers during later development stages (p < 0.05). We also estimated significantly higher returns for shareholders of companies with orphan relative to non-orphan-designated lead drugs from Phase 1 to FDA approval (46% vs. 12%, p < 0.001). Drugs developed across multiple indications also provided higher returns than single-indication agents from Pre-Clinic to FDA approval (21% vs. 11%, p < 0.001). Returns for oncology drugs exceeded other disease areas (26% vs. 8%, p < 0.001).
Clinical and economic conditions surrounding orphan-designated drugs translate to a favorable financial risk-return profile for Bioentrepreneurs and investors. Bioentrepreneurs must be aware of the upside real option value their multi-indication drug could offer when negotiating acquisition or licensing agreements.
AbstractThe COVID-19 pandemic is a global challenge to humankind. To improve the knowledge regarding relevant, efficient and effective COVID-19 measures in health policy, this paper applies a multi-criteria evaluation approach with population, health care, and economic datasets from 19 countries within the OECD. The comparative investigation was based on a Data Envelopment Analysis approach as an efficiency measurement method. Results indicate that on the one hand, factors like population size, population density, and country development stage, did not play a major role in successful pandemic management. On the other hand, pre-pandemic healthcare system policies were decisive. Healthcare systems with a primary care orientation and a high proportion of primary care doctors compared to specialists were found to be more efficient than systems with a medium level of resources that were partly financed through public funding and characterized by a high level of access regulation. Roughly two weeks after the introduction of ad hoc measures, e.g., lockdowns and quarantine policies, we did not observe a direct impact on country-level healthcare efficiency, while delayed lockdowns led to significantly lower efficiency levels during the first COVID-19 wave in 2020. From an economic perspective, strategies without general lockdowns were identified as a more efficient strategy than the full lockdown strategy. Additionally, governmental support of short-term work is promising. Improving the efficiency of COVID-19 countermeasures is crucial in saving as many lives as possible with limited resources.
Schisandra chinensis, an ancient member of the most basal angiosperm lineage which is known as the ANITA, is a fruit-bearing vine with the pharmacological effects of a multidrug system, such as antioxidant, anti-inflammatory, cardioprotective, neuroprotective, anti-osteoporosis effects. Its major bioactive compound is represented by lignans such as schisandrin. Molecular characterization of lignan biosynthesis in S. chinensis is of great importance for improving the production of this class of active compound. However, the biosynthetic mechanism of schisandrin remains largely unknown.
To understand the potential key catalytic steps and their regulation of schisandrin biosynthesis, we generated genome-wide transcriptome data from three different tissues of S. chinensis cultivar Cheongsoon, including leaf, root, and fruit, via long- and short-read sequencing technologies. A total of 132,856 assembled transcripts were generated with an average length of 1.9 kb and high assembly completeness. Overall, our data presented effective, accurate gene annotation in the prediction of functional pathways. In particular, the annotation revealed the abundance of transcripts related to phenylpropanoid biosynthesis. Remarkably, transcriptome profiling during fruit development of S. chinensis cultivar Cheongsoon revealed that the phenylpropanoid biosynthetic pathway, specific to coniferyl alcohol biosynthesis, showed a tendency to be upregulated at the postfruit development stage. Further the analysis also revealed that the pathway forms a transcriptional network with fruit ripening-related genes, especially the ABA signaling-related pathway. Finally, candidate unigenes homologous to isoeugenol synthase 1 (IGS1) and dirigent-like protein (DIR), which are subsequently activated by phenylpropanoid biosynthesis and thus catalyze key upstream steps in schisandrin biosynthesis, were identified. Their expression was increased at the postfruit development stage, suggesting that they may be involved in the regulation of schisandrin biosynthesis in S. chinensis.
Our results provide new insights into the production and accumulation of schisandrin in S. chinensis berries and will be utilized as a valuable transcriptomic resource for improving the schisandrin content.
This research aims to develop an authentic assessment instrument product based on language literacy with a scaffolding model that is oriented towards reading skills. This research method uses research and development methods. The research results show that the preliminary research phase describes the results of curriculum analysis and student analysis. At the product development stage and validation by experts, the percentage of authenticity instrument eligibility consisting of three indicators is 82%. It can be concluded that the instrument is suitable for use in learning activities. The practicality stage given to 20 students in one of the Manyak Payed Public High Schools, Aceh Tamiang District, consisted of four alternative answers, 25% were declared practical. Thus, high school teachers are advised to use the scaffolding model as a solution to improve reading comprehension and language literacy skills.
Insecticide use is an important component of integrated pest management strategies developed for fall armyworm (FAW), Spodoptera frugiperda J.E Smith, control in maize in many African countries. Here, the optimum number of synthetic insecticide and biopesticide applications needed to effectively manage FAW at a minimal cost in maize was studied.
Materials and methods
A 3 × 4 factorial experiment arranged in a split plot design was used. Insecticides [Neem seed oil (NSO), 3% Azadirachtin); Emastar 112 EC (emamectin benzoate 48 g/L + acetamiprid 64 g/L); Eradicoat (282 g/L Maltodextrin)] were on the main plots, while insecticide spraying regimes [untreated control, spraying once (at VE–V5 maize develoment stage), twice (at VE–V5 and V6–V12 stages), thrice (at VE–V5, V6–V12 and V12–VT stages), four times (at VE–V5, V6–V12, V12–VT and R1–R3 stages)] were on the sub-plots.
The results showed that larval infestations were generally lower in Emastar 112 EC treated maize than in those sprayed with Eradicoat or NSO. Infestations were higher in the untreated control (no spray) but decreased with increases in number of spray applications in insecticide treated plots. Again, crop damage was low in Emastar 112 EC treated maize. This variable also decreased with an increase in the number of spray applications. Grain yield was significantly affected by the spraying regime only, with this variable being lowest in the untreated control. In both years, yields were at least 1.5-fold higher in maize sprayed twice, thrice or four times compared to the untreated control. Emastar 112 EC had the highest net economic benefits. A single spray of Emastar 112 EC at the VE–V5 maize development stage resulted in maximum profits, while two sprays (i.e., at VE–V5 and V6–V12 stages) were needed for Eradicoat and NSO.
Hence, synthetic insecticides and biopesticides require different frequency of spray applications for cost effective management of FAW in northern Ghana. These findings are potentially applicable in other sub-Saharan African countries where this pest is present.