• Title/Summary/Keyword: critical target

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High expression of RAD51 promotes DNA damage repair and survival in KRAS-mutant lung cancer cells

  • Hu, Jinfang;Zhang, Zhiguo;Zhao, Lei;Li, Li;Zuo, Wei;Han, Lei
    • BMB Reports
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    • v.52 no.2
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    • pp.151-156
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    • 2019
  • RAD51 recombinase plays a critical role in homologous recombination and DNA damage repair. Here we showed that expression of RAD51 is frequently upregulated in lung cancer tumors compared with normal tissues and is associated with poor survival (hazard ratio (HR) = 2, P = 0.0009). Systematic investigation of lung cancer cell lines revealed higher expression of RAD51 in KRAS mutant (MT) cells compared to wildtype (WT) cells. We further showed that MT KRAS, but not WT KRAS, played a critical role in RAD51 overexpression via MYC. Moreover, our results revealed that KRAS MT cells are highly dependent on RAD51 for survival and depletion of RAD51 resulted in enhanced DNA double strand breaks, defective colony formation and cell death. Together, our results suggest that mutant KRAS promotes RAD51 expression to enhance DNA damage repair and lung cancer cell survival, suggesting that RAD51 may be an effective therapeutic target to overcome chemo/radioresistance in KRAS mutant cancers.

Optimum design of viscous dampers to prevent pounding of adjacent structures

  • Karabork, Turan;Aydin, Ersin
    • Earthquakes and Structures
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    • v.16 no.4
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    • pp.437-453
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    • 2019
  • This study investigates a new optimal placement method for viscous dampers between structures in order to prevent pounding of adjacent structures with different dynamic characteristics under earthquake effects. A relative displacement spectrum is developed in two single degree of freedom system to reveal the critical period ratios for the most risky scenario of collision using El Centro earthquake record (NS). Three different types of viscous damper design, which are classical, stair and X-diagonal model, are considered to prevent pounding on two adjacent building models. The objective function is minimized under the upper and lower limits of the damping coefficient of the damper and a target modal damping ratio. A new algorithm including time history analyses and numerical optimization methods is proposed to find the optimal dampers placement. The proposed design method is tested on two 12-storey adjacent building models. The effects of the type of damper placement on structural models, the critical period ratios of adjacent structures, the permissible relative displacement limit, the mode behavior and the upper limit of damper are investigated in detail. The results of the analyzes show that the proposed method can be used as an effective means of finding the optimum amount and location of the dampers and eliminating the risk of pounding.

Protective Effect of Right Ventricular Mitochondrial Damage by Cyclosporine A in Monocrotaline-induced Pulmonary Hypertension

  • Lee, Dong Seok;Jung, Yong Wook
    • Korean Circulation Journal
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    • v.48 no.12
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    • pp.1135-1144
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    • 2018
  • Background and Objectives: Mitochondria play a key role in the pathophysiology of heart failure and mitochondrial permeability transition pore (MPTP) play a critical role in cell death and a critical target for cardioprotection. The aim of this study was to evaluate the protective effects of cyclosporine A (CsA), one of MPTP blockers, and morphological changes of mitochondria and MPTP related proteins in monocrotaline (MCT) induced pulmonary arterial hypertension (PAH). Methods: Eight weeks old Sprague-Dawley rats were randomized to control, MCT (60 mg/kg) and MCT plus CsA (10 mg/kg/day) treatment groups. Four weeks later, right ventricular hypertrophy (RVH) and morphological changes of right ventricle (RV) were done. Western blot and reverse transcription polymerase chain reaction (RT-PCR) for MPTP related protein were performed. Results: In electron microscopy, CsA treatment prevented MCT-induced mitochondrial disruption of RV. RVH was significantly increased in MCT group compared to that of the controls but RVH was more increased with CsA treatment. Thickened medial wall thickness of pulmonary arteriole in PAH was not changed after CsA treatment. In western blot, caspase-3 was significantly increased in MCT group, and was attenuated in CsA treatment. There were no significant differences in voltage-dependent anion channel, adenine nucleotide translocator 1 and cyclophilin D expression in western blot and RT-PCR between the 3 groups. Conclusions: CsA reduces MCT induced RV mitochondrial damage. Although, MPTP blocking does not reverse pulmonary pathology, it may reduce RV dysfunction in PAH. The results suggest that it could serve as an adjunctive therapy to PAH treatment.

A parameter sweep approach for first-cut design of 5 MW Ship propulsion motor

  • Bong, Uijong;An, Soobin;Im, Chaemin;Kim, Jaemin;Hahn, Seungyong
    • Progress in Superconductivity and Cryogenics
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    • v.21 no.1
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    • pp.25-30
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    • 2019
  • This paper presents a conceptual design approach of air-cored synchronous machine with high temperature superconductor (HTS) field winding. With a given configuration of a target machine, boundary conditions are set in the cylindrical coordinate system and analytic field calculation is performed by solving a governing equation. To set proper boundary conditions, current distributions of the field winding and the armature winding are expressed by the Fourier expansion. Based on analytic magnetic field calculation results, key machine parameters are calculated: 1) inductance, 2) critical current of field winding, 3) weight, 4) HTS conductor consumption, and 5) efficiency. To investigate all potential design options, 6 sweeping parameters are determined to characterize the geometry of the machine and the parameter calculation process is performed for each design options. Among design options satisfying constraints including >80 % critical current margin and >95 % efficiency, in this paper, a first-cut design was selected in terms of overall machine weight and HTS conductor consumption to obtain a lightweight and economical design. The goal is to design a 5-MW machine by referring to the same capacity machine that was previously constructed by another group. Our design output is compared with finite element method (FEM) simulation to validate our design approach.

A Study on Optimized Placement of Green-Gray Infrastructure for Effective Flood Mitigation (효과적인 도시 홍수 저감을 위한 그린-그레이 인프라 위치 설정에 관한 연구)

  • Bae, Chae-Young;Lee, Dong-Kun
    • Journal of the Korean Society of Environmental Restoration Technology
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    • v.25 no.6
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    • pp.65-75
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    • 2022
  • Urban flood management(UFM) strategy ought to consider the connections and interactions between existing and new infrastructures to manage stormwater and improve the capacity to treat water. It is also important to demonstrate strategies that can be implemented to reduce the flow at flooding sources and minimize flood risk at critical locations. Although the general theory of spatial impact is popular, modeling guidelines that can provide information for implementation in real-world plans are still lacking. Under such background, this study conducted a modeling research based on an actual target site to confirm the hypothesis that it is appropriate to install green infrastructure(GI) in the source area and to take structural protection measures in the impact area, as summarized in previous studies. The results of the study proved the hypothesis, but the results were different from the hypothesis depending on which hydrological performance indicators were targeted. This study will contribute to demonstrating the effectiveness of strategies that can be implemented to reduce the flow at flooding sources and minimize the risk of flooding in critical locations in terms of spatial planning and regeneration.

Development of a Blood Glucose Control Protocol for Medical ICU Patients (내과 중환자실 환자의 혈당조절 프로토콜 개발)

  • Kim, Eun Sung;Choi-Kwon, Smi
    • Journal of Korean Clinical Nursing Research
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    • v.15 no.3
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    • pp.27-38
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    • 2009
  • Purpose: The purpose of this study was to develop a blood glucose control protocol for medical intensive care unit (ICU) patients. Methods: The blood glucose control protocol was developed through the following process: selection of preliminary protocols, clinical application, and evaluation. The clinical validity of the protocol was measured by application, along with examination of the effects of the Yale and the Mayo blood glucose protocols. Seventeen medical ICU adults patients whose blood glucose levels exceeded 200 mg/dL consecutively participated in the study. The development protocol was evaluated by an expert group. Results: Incidence of normal blood glucose levels (p=.041) increased significantly in the Yale protocol application group. Also, incidence of severe hyperglycemia (p=.029) decreased significantly and time to target range of glucose (p=.023) decreased significantly after application of the Yale protocol. However, there was no significant difference in incidence of hypoglycemia (p=.666) between three groups. Conclusion: Using the developed protocol as a basis for the modified Yale protocol was found to be effective in improving the state of blood glucose control for medical ICU patients and is expected to be used for nursing intervention in critical care.

A Pumilio Activity Sensor Reveals Bag-of-Marbles Inhibition of Pum Activity in the Drosophila Ovary

  • Wijeong Jang;Changsoo Kim
    • Development and Reproduction
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    • v.27 no.1
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    • pp.39-46
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    • 2023
  • Pumilio (Pum) is an RNA-binding protein and translational repressor important to diverse biological processes. In the Drosophila ovary, Pum is expressed in female germline stem cells (GSCs), wherein it acts as an intrinsic stem cell maintenance factor via repressing target mRNAs that are as yet mostly unknown. Pum recognizes the Pum binding sequence (PBS) in the mRNA 3'UTR through its C-terminus Puf domain. Translational repression is mediated through its N-terminal domain, but the molecular mechanism remains largely unknown. We previously showed that Bag-of-marbles, a critical differentiation-promoting factor of female GSCs, physically interacts with the N-terminus of Pum. We further showed that this interaction is critical to Bam inhibition of Pum repressive action in cultured cells, but the physiological relevance was not addressed. Here we design an in vivo GFP translational reporter bearing the PBS in its 3'UTR and show that GFP expression is reduced in cells wherein Pum is known to be active. Furthermore, we demonstrate in pum mutant ovary that this GFP repression requires Pum, and also that the sensor faithfully monitors Pum activity. Finally, we show that forced expression of Bam inhibits Pum-mediated repression, validating that Bam inhibits Pum activity in vivo.

Air-Launched Weapon Engagement Zone Development Utilizing SCG (Scaled Conjugate Gradient) Algorithm

  • Hansang JO;Rho Shin MYONG
    • Korean Journal of Artificial Intelligence
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    • v.12 no.2
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    • pp.17-23
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    • 2024
  • Various methods have been developed to predict the flight path of an air-launched weapon to intercept a fast-moving target in the air. However, it is also getting more challenging to predict the optimal firing zone and provide it to a pilot in real-time during engagements for advanced weapons having new complicated guidance and thrust control. In this study, a method is proposed to develop an optimized weapon engagement zone by the SCG (Scaled Conjugate Gradient) algorithm to achieve both accurate and fast estimates and provide an optimized launch display to a pilot during combat engagement. SCG algorithm is fully automated, includes no critical user-dependent parameters, and avoids an exhaustive search used repeatedly to determine the appropriate stage and size of machine learning. Compared with real data, this study showed that the development of a machine learning-based weapon aiming algorithm can provide proper output for optimum weapon launch zones that can be used for operational fighters. This study also established a process to develop one of the critical aircraft-weapon integration software, which can be commonly used for aircraft integration of air-launched weapons.

Artificial Intelligence-Based Descriptive, Predictive, and Prescriptive Coating Weight Control Model for Continuous Galvanizing Line

  • Devraj Ranjan;G. R. Dineshkumar;Rajesh Pais;Mrityunjay Kumar Singh;Mohseen Kadarbhai;Biswajit Ghosh;Chaitanya Bhanu
    • Corrosion Science and Technology
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    • v.23 no.3
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    • pp.228-234
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    • 2024
  • Zinc wiping is a phenomenon used to control zinc-coating thickness on steel substrate during hot dip galvanizing by equipment called air knife. Uniformity of zinc coating weight in length and width profile along with surface quality are most critical quality parameters of galvanized steel. Deviation from tolerance level of coating thickness causes issues like overcoating (excess consumption of costly zinc) or undercoating leading to rejections due to non-compliance of customer requirement. Main contributor of deviation from target coating weight is dynamic change in air knives equipment setup when thickness, width, and type of substrate changes. Additionally, cold coating measurement gauge measure coating weight after solidification but are installed down the line from air knife resulting in delayed feedback. This study presents a coating weight control model (Galvantage) predicting critical air knife parameters air pressure, knife distance from strip and line speed for coating control. A reverse engineering approach is adopted to design a predictive, prescriptive, and descriptive model recommending air knife setups that estimate air knife distance and expected coating weight in real time. Implementation of this model eliminates feedback lag experienced due to location of coating gauge and achieving setup without trial-error by operator.

Comparison of the Effectiveness of Disinfection According to the Permanence of X-ray Irradiation for Preservation of Water-logged Cultural Heritages (수침 문화재 보존 처리에 있어 엑스선 조사의 연속성에 따른 살균력 효과 비교)

  • GyeongSeo Jo;YeongHyeok Kwak;MyeonJu Lee;Rea-Dong Jeong;Hae-Jun Park
    • Journal of Radiation Industry
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    • v.17 no.4
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    • pp.533-542
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    • 2023
  • We developed an emergency national manual for preservation of cultural heritage using irradiation disinfection technic under flood disaster. And we examined its practicality with a critical radiation dose on fungi that occur at water-logged event in order to prevent fungal damage that occurs during submersion. The X-ray irradiation for this experiment was conducted at the Production Technology Research Institute located in Yeongcheon, Gyeongsangbuk-do. A disinfection critical dose of 12 kGy was selected for two types of fungi known to spread rapidly and are resistant to radiation to submerged cultural properties, and this experiments were conducted by setting a target dose of 12kGy at 8.37mA at 5MeV. Under the above conditions, only continuity of irradiated samples were completely disinfected. This suggests that continuity of irradiation is important for fungal disinfection.