stage development
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2022 ◽  
Vol 16 (4) ◽  
pp. 17-25
Author(s):  
V. O. Kuznetsov

The article provides the periodization of the development of forensic linguistics as one of the primary forms of application of specialized linguistic knowledge in legal proceedings. The author distinguishes four main stages: the 1st stage – the emergence of forensic linguistic expertise, the 2nd stage – its formation, the 3rd stage - development, and the 4th stage - improvement. Finally, at a more generalized alternative periodization (before-the-expert/philological and expert stages), the author reveals pressing issues of developing this kind of expertise and the prospects for its evolution.


2022 ◽  
Vol 61 ◽  
pp. 102602
Author(s):  
Teis Boderskov ◽  
Michael Bo Rasmussen ◽  
Christian Hein Cassard ◽  
Julie Svensgaard ◽  
Laurids Nørskov Enevoldsen ◽  
...  

Author(s):  
Chatpong Pethrak ◽  
Navaporn Posayapisit ◽  
Jutharat Pengon ◽  
Nattida Suwanakitti ◽  
Atiporn Saeung ◽  
...  

Antifolates targeting dihydrofolate reductase (DHFR) are antimalarial compounds that have long been used for malaria treatment and chemoprevention (inhibition of infection from mosquitoes to humans). Despite their extensive applications, the thorough understanding of antifolate activity against hepatic malaria parasites, especially resistant parasites, have yet to be achieved. Using a transgenic P. berghei harboring quadruple mutant dhfr from P. falciparum (Pb::Pfdhfr -4M ) , we demonstrate that quadruple mutations on Pfdhfr confer complete chemoprevention resistance to pyrimethamine, the previous generation of antifolate, but not to a new class of antifolate designed to overcome the resistance such as P218. Detailed investigation to pin-point stage-specific chemoprevention further demonstrated that it is unnecessary for the drug to be present throughout hepatic development. The drug is most potent against the developmental stages from early hepatic trophozoite to late hepatic trophozoite, but is not effective at inhibiting sporozoite and early hepatic stage development from sporozoite to early trophozoite. Our data shows that P218 also inhibited the late hepatic stage development, from trophozoite to mature schizonts to a lesser extent. With a single dose of 15 mg/kg, P218 prevented infection from up to 25,000 pyrimethamine-resistant sporozoites, a number equal to thousands of infectious mosquito bites. Additionally, the hepatic stage of malaria parasite is much more susceptible to antifolates than the asexual blood stage. This study provides important insights into the activity of antifolates, as a chemopreventive therapeutic which could lead to a more efficient and cost effective treatment regime.


2021 ◽  
Vol 20 (4) ◽  
pp. 358-379
Author(s):  
Hoyoung Kwon ◽  
Jai S. Mah

Abstract In the early stages of its transition, Turkmenistan pursued a gradualist path. Diversification, industrialization, and market-based reforms led to very rapid economic growth particularly since the late 2000s. This article investigates the role of Turkmenistan’s economic development policy in diversifying industries and promoting the manufacturing sector. The government has diversified the destinations for the natural gas exports. Although its agriculture had been characterized as cotton monoculture, the share of wheat has risen since the 1990s. The textile industry has led the manufacturing sector, and other industries are not well developed. The government has successfully attracted foreign direct investment. Turkmenistan’s trade policy has contributed to supplying machines for manufactured products, although it might have been harmful to the early-stage development of the manufacturing sector. Turkmenistan, which is not a member of the WTO, may actively utilize its policy space to promote technology-intensive industries and must strengthen its level of human capital.


Author(s):  
Deop Darius ◽  
Abd Jamal ◽  
Putri Bintusy Syathi

The decentralization of Indonesia allowed the development in the regency level to improve to the highest level. However, the impact can only be maximized by utilizing the potential economy embodied in the regent. This study investigates the development of the Pasaman Regency by analyzing the potential sector and the stage development of the sector. Therefore, this study uses mixed research methods with explorative approaches and uses Contribution Sectors Analysis, Location Quotient Analysis model, Shift Share Analysis model, and Klassen typological analysis model, The data used is the Gross Regional Domestic Product (GRDP) of Pasaman Regency and West Sumatra Province in the period 2010 until 2019 and data on the production of the Pasaman Regency base sector in each district in 2015-2019. The result showed that the agricultural, fisheries, and forestry sectors have the largest contribution to the GRDP of Pasaman Regency which is 55.51%, then the sector that belongs to the base sector with the value of LQ>1, namely the agricultural, fisheries, and forestry sectors. The sectors that experienced a net change or shift and had a positive value and the highest level of excellence were the agricultural, fisheries, and forestry sectors of 10,718,410,000. Klassen Typology Analysis is based on the base sector, namely the agricultural, fisheries, and forestry sectors with the largest contribution to the fisheries sector so that the grouping of regions using fisheries data with the results of Panti and South Rao Districts is classified as advanced areas and Lubuk Sikaping and Mapat Tunggul Selatan districts are classified as lagging areas. There is a shift in territory caused by land transfer, changes in the profession, and accessibility. The development of district areas in Pasaman Regency through the fishery sector in the form of fish cultivation, fish feed factories, and fish processing industries is expected to improve the welfare of the community, especially sub-districts that are not classified as developed areas so that the trickle-down effect and the realization of equitable distribution


2021 ◽  
Vol 10 (3) ◽  
pp. 404-415
Author(s):  
Murti Wida Ningsih ◽  
Neta Dian Lestari ◽  
Depi Pramika

This study used the Rowntree model with several stages such as: planning stage, development stage, and evaluation stage. This research is included in the Research & Development (R&D) research where the method used to produce a particular product and assess the product is by collecting data using an initial test (Pre-test) and a final test (Post-test). Collecting data in this study used observation, interviews, questionnaires, and tests. The data analysis technique used descriptive data analysis by assessing the product both from the media and the use of the product and assessing the scale used to find out the results of the product using Likert. With the stages of product testing by material experts, and media experts, so that the results of the study showed that accounting pocket books showed the validity of pocket books from material experts with an average result of 94% being in very valid criteria, media experts with an average result of 95% being in very valid criteria.The results of student comments and suggestions stage one by one, that the accounting pocket book was interesting and practical, while the small group stage with an average result of 89% was in very practical criteria and field test results were on average 85% in very practical criteria.


2021 ◽  
Author(s):  
Omobukola Solebo ◽  
Liqin Ling ◽  
Jing Zhou ◽  
Tian-Min Fu ◽  
Hangjun Ke

It is widely accepted that glycolysis alone is sufficient to support the energy demand of intraerythrocytic malaria parasites when they grow inside RBCs. However, here we show that the metabolic by-product pyrophosphate (PPi) is a critical energy source for ring stage development and the transition from the ring to trophozoite stage. During early phases of the asexual lifecycle, the parasite utilizes PfVP1 (Plasmodium falciparum vacuolar pyrophosphatase 1), an ancient PPi-driven proton pump, to pump protons across the parasite plasma membrane to maintain the membrane potential and cytosolic pH. Conditional deletion of PfVP1 leads to delayed ring stage development and a complete blockage of the ring to trophozoite transition, which can be partially rescued by Arabidopsis thaliana vacuolar pyrophosphatase 1, but not by the soluble pyrophosphatase from Saccharomyces cerevisiae. Proton-pumping pyrophosphatases are absent in humans and animals, which highlights the possibility of developing highly selective VP1 inhibitors against the malaria parasite.


PLoS Biology ◽  
2021 ◽  
Vol 19 (10) ◽  
pp. e3001434
Author(s):  
Kevin J. Hart ◽  
B. Joanne Power ◽  
Kelly T. Rios ◽  
Aswathy Sebastian ◽  
Scott E. Lindner

Productive transmission of malaria parasites hinges upon the execution of key transcriptional and posttranscriptional regulatory events. While much is now known about how specific transcription factors activate or repress sexual commitment programs, far less is known about the production of a preferred mRNA homeostasis following commitment and through the host-to-vector transmission event. Here, we show that in Plasmodium parasites, the NOT1 scaffold protein of the CAF1/CCR4/Not complex is duplicated, and one paralogue is dedicated for essential transmission functions. Moreover, this NOT1-G paralogue is central to the sex-specific functions previously associated with its interacting partners, as deletion of not1-g in Plasmodium yoelii leads to a comparable or complete arrest phenotype for both male and female parasites. We show that, consistent with its role in other eukaryotes, PyNOT1-G localizes to cytosolic puncta throughout much of the Plasmodium life cycle. PyNOT1-G is essential to both the complete maturation of male gametes and to the continued development of the fertilized zygote originating from female parasites. Comparative transcriptomics of wild-type and pynot1-g− parasites shows that loss of PyNOT1-G leads to transcript dysregulation preceding and during gametocytogenesis and shows that PyNOT1-G acts to preserve mRNAs that are critical to sexual and early mosquito stage development. Finally, we demonstrate that the tristetraprolin (TTP)-binding domain, which acts as the typical organization platform for RNA decay (TTP) and RNA preservation (ELAV/HuR) factors is dispensable for PyNOT1-G’s essential blood stage functions but impacts host-to-vector transmission. Together, we conclude that a NOT1-G paralogue in Plasmodium fulfills the complex transmission requirements of both male and female parasites.


Agronomy ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 2058
Author(s):  
Iván P. Ordóñez ◽  
Ignacio F. López ◽  
Peter D. Kemp ◽  
Daniel J. Donaghy ◽  
Yongmei Zhang ◽  
...  

The increase in drought events due to climate change have enhanced the relevance of species with greater tolerance or avoidance traits to water restriction periods, such as Bromus valdivianus Phil. (B. valdivianus). In southern Chile, B. valdivianus and Lolium perenne L. (L. perenne) coexist; however, the pasture defoliation criterion is based on the physiological growth and development of L. perenne. It is hypothesised that B. valdivianus needs a lower defoliation frequency than L. perenne to enhance its regrowth and energy reserves. Defoliation frequencies tested were based on B. valdivianus leaf stage 2 (LS-2), leaf stage 3 (LS-3), leaf stage 4 (LS-4) and leaf stage 5 (LS-5). The leaf stage development of Lolium perenne was monitored and contrasted with that of B. valdivianus. The study was conducted in a glasshouse and used a randomised complete block design. For Bromus valdivianus, the lamina length, photosynthetic rate, stomatal conductance, tiller number per plant, leaf area, leaf weights, root growth rate, water-soluble carbohydrates (WSCs) and starch were evaluated. Bromus valdivianus maintained six live leaves with three leaves growing simultaneously. When an individual tiller started developing its seventh leaf, senescence began for the second leaf (the first relevant leaf for photosynthesis). Plant herbage mass, the root growth rate and tiller growth were maximised at LS-4 onwards. The highest leaf elongation rate, evaluated through the slope of the lamina elongation curve of a fully expanded leaf, was verified at LS-4. The water-soluble carbohydrates (WSCs) increased at LS-5; however, no statistical differences were found in LS-4. The LS-3 and LS-2 treatments showed a detrimental effect on WSCs and regrowth. The leaf photosynthetic rate and stomatal conductance diminished while the leaf age increased. In conclusion, B. valdivianus is a ‘six-leaf’ species with leaf senescence beginning at LS-4.25. Defoliation at LS-4 and LS-5 was optimum for plant regrowth, maximising the aboveground plant parameters and total WSC accumulation. The LS-4 for B. valdivianus was equivalent to LS-3.5 for L. perenne. No differences related to tiller population in B. valdivianus were found in the different defoliation frequencies.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mohammad Enamul Hoque Kayesh ◽  
Michinori Kohara ◽  
Kyoko Tsukiyama-Kohara

Dengue is the most prevalent and rapidly spreading mosquito-borne viral disease caused by dengue virus (DENV). Recently, DENV has been affecting humans within an expanding geographic range due to the warming of the earth. Innate immune responses play a significant role in antiviral defense, and Toll-like receptors (TLRs) are key regulators of innate immunity. Therefore, a detailed understanding of TLR and DENV interactions is important for devising therapeutic and preventive strategies. Several studies have indicated the ability of DENV to modulate the TLR signaling pathway and host immune response. Vaccination is considered one of the most successful medical interventions for preventing viral infections. However, only a partially protective dengue vaccine, the first licensed dengue vaccine CYD-TDV, is available in some dengue-endemic countries to protect against DENV infection. Therefore, the development of a fully protective, durable, and safe DENV vaccine is a priority for global health. Here, we demonstrate the progress made in our understanding of the host response to DENV infection, with a particular focus on TLR response and how DENV avoids the response toward establishing infection. We also discuss dengue vaccine candidates in late-stage development and the issues that must be overcome to enable their success.


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