• The Korean Journal of Pesticide Science
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• v.5 no.3
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• pp.1-11
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• 2001

New technologies will have a large impact on the discovery of new herbicide site of action. Genomics, combinatorial chemistry, and bioinformatics help take advantage of serendipity through tile sequencing of huge numbers of genes or the synthesis of large numbers of chemical compounds. There are approximately $10^{30}\;to\;10^{50}$ possible molecules in molecular space of which only a fraction have been synthesized. Combining this potential with having access to 50,000 plant genes in the future elevates tile probability of discovering flew herbicidal site of actions. If 0.1, 1.0 or 10% of total genes in a typical plant are valid for herbicide target, a plant with 50,000 genes would provide about 50, 500, and 5,000 targets, respectively. However, only 11 herbicide targets have been identified and commercialized. The successful design of novel herbicides depends on careful consideration of a number of factors including target enzyme selections and validations, inhibitor designs, and the metabolic fates. Biochemical information can be used to identify enzymes which produce lethal phenotypes. The identification of a lethal target site is an important step to this approach. An examination of the characteristics of known targets provides of crucial insight as to the definition of a lethal target. Recently, antisense RNA suppression of an enzyme translation has been used to determine the genes required for toxicity and offers a strategy for identifying lethal target sites. After the identification of a lethal target, detailed knowledge such as the enzyme kinetics and the protein structure may be used to design potent inhibitors. Various types of inhibitors may be designed for a given enzyme. Strategies for the selection of new enzyme targets giving the desired physiological response upon partial inhibition include identification of chemical leads, lethal mutants and the use of antisense technology. Enzyme inhibitors having agrochemical utility can be categorized into six major groups: ground-state analogues, group specific reagents, affinity labels, suicide substrates, reaction intermediate analogues, and extraneous site inhibitors. In this review, examples of each category, and their advantages and disadvantages, will be discussed. The target identification and construction of a potent inhibitor, in itself, may not lead to develop an effective herbicide. The desired in vivo activity, uptake and translocation, and metabolism of the inhibitor should be studied in detail to assess the full potential of the target. Strategies for delivery of the compound to the target enzyme and avoidance of premature detoxification may include a proherbicidal approach, especially when inhibitors are highly charged or when selective detoxification or activation can be exploited. Utilization of differences in detoxification or activation between weeds and crops may lead to enhance selectivity. Without a full appreciation of each of these facets of herbicide design, the chances for success with the target or enzyme-driven approach are reduced.

• The Korean Journal of Food And Nutrition
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• v.16 no.3
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• pp.180-186
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• 2003

In order to prediction of lethal effects on target microorganisms, this study was developed the program in the basis of Excel that was systemized with Visual Basic. This program was automatically calculated the lethal effects (L and Fo value) by using thermal characteristics (D and z value), kinetic model and mathematic model. For the selection of target microorganisms, we are selected two microorganisms because of spoilage increasing by acid production and decreasing quality of food, and heat resistance microorganisms. The target microorganisms were Bacillus cereus (D$_{121.1}$=0.0065 min, z=7.8$^{\circ}C$) and Bacillus subtilis (D$_{121.1}$=0.5 min, z =12$^{\circ}C$). The program was developed for the target microorganisms, and that was very useful for various microorganisms that direct introducing known D and z value.

• The Korean Journal of Soil Zoology
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• v.1 no.2
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• pp.81-88
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• 1996

Entomopathogenic nematodes, Steinernema carpocapsae, was able to invade and kill the several lepidopteran pests including the beet armyworm, Spodeptera exigua Hubner, which was the most effective target host. The beet armyworms treated with the effective nematode concentrations were died within 48 hrs. The lethal effect of the nematode was varied among the developmental stages of the host. The fifth instar larvae of the beet armyworm was more vulnerable to the nematode than the third instar larvae. Pupae was, however, refractory to the nematode. All three bioessays (topical application, filter paper test, and soil treatment) showed the positive correlation between the number of the treated nematodes and the mortality of the host. Topical application was the most effective and fast-acting method so that it gave the lethal effect 2 days earlier than did filter paper test at the same number of the treated nematodes. Soil treatment required higher number of the nematodes to get the effective lethality than did filter paper test. The fifth instar larvae of the beet armyworm expressed the specific hemolymph proteins of 5 to 10 kDa in response to nematode infection.

• Korean Journal of Microbiology
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• v.41 no.4
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• pp.275-280
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• 2005

Anthrax is an infectious disease caused by the gram-positive bacterium, Bacillus anthracis. Anthrax toxin is a tripartite toxin comprising of protective antigen (PA), lethal factor (LF) and edema factor (EF). PA is the receptor-binding component, which facilitates the entry of LF or EF onto the cytosol. LF is a zinc-dependent metalloprotease, which is a critical virulence factor in cytotoxicity of infected animals. Therefore, it is of interest to develop its potent inhibitors for the neutralization of anthrax toxin. The first step to identify the inhibitors is the development of a rapid, sensitive, and simple assay method with a high-throughput ability. Much efforts have been concentrated on the preparation of powerful assays and on the screening of inhibitors using these system. In the present study, we have tried to construct anthrax lethal factor in yeast expression system to prepare cell-based high-throughput assay system. Here, we have shown the results covering the construction of a new vector system, subcloning of LF gene, and the expression of target gene. Our results are first trial to express LF gene in eukaryote and provide the basic steps in design of cell-based assay system.

• Toxicological Research
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• v.22 no.2
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• pp.117-126
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• 2006

This study was conducted to obtain the acute information of the oral dose toxicity of lyophilized water extract of Picrorrhiza Rhizoma (PR) - dried underground stem of Picrorrhiza kurroa, having various pharmacological effects, in male and female mice. In order to calculate 50% lethal dose ($LD_{50}$), approximate lethal dose and target organs, test article was administered once by oral gavage to male and female ICR mice at 2000, 1000, 500 and 250 mg/kg. The mortality and changes on body weight, clinical signs and gross observation were monitored during 14 days after dosing with organ weight and histopathology of 12 types of principle organs. As the results, we could not find any mortality, clinical signs, changes in the body weight and gross findings except for hair loss, a significantly (p<0.05) increase of body weight gains in 2000mg/kg of PR extracts-dosing male group and some sporadic gross findings. In addition, no meaningful changes on the organ weight and histopathology of 12 types of principle organs were detected in the present study except for significantly (p<0.05) but dose independent changes on thymus, spleen and popliteal lymph nodes weights, and some sporadic accidental histopathological findings. The results obtained in this study suggest that the PR extract is non-toxic in mice and is therefore likely to be safe for clinical use. The $LD_{50}$ and approximate lethal dose of PR extracts in both female and male mice were considered as over 2000 mg/kg.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2447-2451
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• 2014

Human papillomavirus (HPV) is the primary etiologic agent of cervical cancer. Consideration of safety and non human leukocyte antigen restriction, protein vaccine has become the most likely form of HPV therapeutic vaccine, although none have so far been reported as effective. Since tumor cells consistently express the two proteins E6 and E7, most therapeutic vaccines target one or both of them. In this study, we fabricated DC vaccines by transducing replication-defective recombinant adenoviruses expressing E6/E7 fusion gene of HPV-16, to investigate the lethal effects of specific cytotoxic T lymphocytes (CTL) against CaSki cells in vitro. Mouse immature dendritic cells (DC) were generated from bone marrow, and transfected with pAd-E6/E7 to prepare a DC vaccine and to induce specific CTL. The surface expression of CD40, CD68, MHC II and CD11c was assessed by flow cytometry (FCM), and the lethal effects of CTL against CaSki cells were determined by DAPI, FCM and CCK-8 methods. Immature mouse DC was successfully transfected by pAd-E6/E7 in vitro, and the transfecting efficiency was 40%-50%. A DC vaccine was successfully prepared and was used to induce specific CTL. Experimental results showed that the percentage of apoptosis and killing rate of CaSki cells were significantly increased by coculturing with the specific CTL (p <0.05). These results illustrated that a DC vaccine modified by HPV-16 E6/E7 gene can induce apoptosis of CaSki cells by inducing CTL, which may be used as a new strategy for biological treatment of cervical cancer.

• Journal of the Computational Structural Engineering Institute of Korea
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• v.30 no.6
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• pp.501-506
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• 2017

An infrared seeking missile does not emit any signal by itself as it is guided by passive heat signature from an aircraft. Therefore, it is difficult for the target aircraft to notice the existence of incoming missile, making it a serious threat. The usage of MAW(missile approach warning) that can notify the approaching infrared seeking missile is currently limited due to its high cost. Furthermore, effectiveness of MAW against infrared seeking missile is not available in open literature. Therefore, effect of evasive maneuver by MAW on the survivability of the aircraft is simulated to evaluate the benefit of the MAW in this research. The lethal range is used as a measure of aircraft survivability. An aircraft flying at an altitude of 5km with Mach 0.9 being tracked by air-launched AIM-9 infrared seeking missile is considered in this research. As a variable for the evasive maneuver, the MAW recognition distance of 5~7km and the G-force of 3~7G that limits maximum directional change of the aircraft are considered. Simulation results showed that the recognition of incoming missile by MAW and following evasive maneuver can reduce the lethal range considerably. Maximum reduction in lethal range is found to be 29.4%. Also, the MAW recognition distance have a greater importance than the aircraft maneuverability that is limited by structural limit of the aircraft.

• Bulletin of the Korean Chemical Society
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• v.33 no.1
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• pp.221-226
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• 2012

DNA-functionalized silver and silver/gold bimetallic nanoparticle superstructure probes with controllable sizes and optical properties are synthesized using monothiol DNA and dithiothreitol. The superstructures exhibit a very narrow size distribution, which can be easily controlled by balancing the ratio of dithiothreitol and DNA. These superstructures assemble reversibly in a highly cooperative manner, and are SERS active. Multiplexed colorimetric detection of DNA targets using these superstructure probes has been demonstrated to identify three different DNA target sequences that are associated with three lethal diseases, respectively.

• Korean Journal of Head & Neck Oncology
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• v.38 no.1
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• pp.1-9
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• 2022

Thyroid cancer is one of the slow-growing tumors with excellent oncological outcomes. However, a small set of patients with unexpectedly severe outcomes are usually ignored. Anaplastic thyroid cancer (ATC) remains one of the most aggressive and lethal solid tumors. Recently, dabrafenib and trametinib combination therapy or neoadjuvant BRAF induction therapy has shown promising results. In addition, a combination of targeted drugs, immunotherapy, surgery, and radiation therapy can improve overall survival in ATC patients. Another disease for which there is no breakthrough treatment is radioactive iodine-refractory differentiated thyroid cancer (DTC). To date, multikinase inhibitors (sorafenib, lenvatinib) targeting the growth factor signaling pathway have been developed and approved as anticancer agents for patients with advanced DTC. This review includes results from multikinase inhibitors to the emergence of new target molecules, including rearrangements during transformation (RET) and tropomyosin receptor kinase (TRK).

• The Journal of Internal Korean Medicine
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• v.26 no.2
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• pp.369-378
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• 2005

An herbal water extract of Bojungikkeehapdaechilkitang(BDT) was prepared to test it for single-dose and repeated-dose toxicity, genotoxicity and reproductive toxicity, and to obtain a 50% lethal dose$(LD_{50})$, approximated lethal dose(ALD), and approximated target organs for BDT. The extract was tested on female and male ICR mice according to KFDA Guideline 1999-61 at doasge level of 2000, 1000, 500, 250 and 125mg/kg/10mL In this study, clinical signs, mortalities and gross findings of principal organs were observed for 14 days of single dosing, and afterwards in some cases. The ALD and $LD_{50}$ of BDT extract obtained in this study was>2000mg/kg for both male and female ICR mice. Also, any possible digestive toxicity of BDT extract was found to be above 1000mg/kg in both male and female ICR mice. The results of this study strongly suggest that BDT extract has no toxic effect at dosage level below 500mg/kg.