• Title/Summary/Keyword: Dual activity

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High Affinity Pharmacological Profiling of Dual Inhibitors Targeting RET and VEGFR2 in Inhibition of Kinase and Angiogeneis Events in Medullary Thyroid Carcinoma

  • Dunna, Nageswara Rao;Kandula, Venkatesh;Girdhar, Amandeep;Pudutha, Amareshwari;Hussain, Tajamul;Bandaru, Srinivas;Nayarisseri, Anuraj
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.16
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    • pp.7089-7095
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    • 2015
  • Clinical evidence shows that dual inhibition of kinases as well angiogenesis provides ideal therapeutic option in the treatment of medullary thyroid carcinoma (MTC) than inhibiting either of these with the events separately. Although treatment with dual inhibitors has shown good clinical responses in patients with MTC, it has been associated with serious side effects. Some inhibitors are active agents for both angiogenesis or kinase activity. Owing to narrow therapeutic window of established inhibitors, the present study aims to identify high affinity dual inhibitors targeting RET and VEGFR2 respectively for kinase and angiogenesis activity. Established inhibitors like Vandetanib, Cabozantinib, Motesanib, PP121, RAF265 and Sunitinib served as query parent compounds for identification of structurally similar compounds by Tanimoto-based similarity searching with a threshold of 95% against the PubChem database. All the parent inhibitors and respective similar compounds were docked against RET and VEGFR2 in order to retrieve high affinity compounds with these two proteins. AGN-PC-0CUK9P PubCID: 59320403 a compound related to PPI21 showed almost equal affinity for RET and VEGFR2 and unlike other screened compounds with no apparent bias for either of the receptors. Further, AGNPC- 0CUK9P demonstrated appreciable interaction with both RET and VEGFR2 and superior kinase activity in addition to showed optimal ADMET properties and pharmacophore features. From our in silico investigation we suggest AGN-PC-0CUK9P as a superior dual inhibitor targeting RET and VEGFR2 with high efficacy which should be proposed for pharmacodynamic and pharmacokinetic studies for improved treatment of MTC.

Effect of Body Weight and Dual Effect of X-ray Irradiation on Tryptophan Pyrrolase Activity (TPO 활성에 대한 체중 변화의 영향과 X-선에 의한 이원적 영향)

  • Jung, Noh-Pal;Kim, Dong-Jun
    • The Korean Journal of Physiology
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    • v.5 no.1
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    • pp.19-22
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    • 1971
  • The effect based upon changes of body weight and effect of X-ray irradiation on tryptophan pyrrolase (TPO) activity in liver homogenate of albino rats was studied. 1. The average TPO activity of control group of 33 rats weighing $95{\sim}172g$\;was\;2.372{\pm}0.165{\mu}$ moles kynurenine/g protein/hr. 2. Correlation between body weight of 33 rats and its TPO activity was not showed practically(r=0.011). 3. TPO activity of whole-body X-ray irradiated rats (700r) was increased about double at 3hours and increased for a period of 4 days after irradiation, but after 6 days it was decreased gradually. This result is that whole-body X-ray irradiation showed dual effect on TPO activity in rat liver.

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Function of the Tethered rec-eCG in Rat and Equine Receptors

  • Park, Jong-Ju;Jargal, Naidansuren;Yoon, Jong-Taek;Min, Kwan-Sik
    • Reproductive and Developmental Biology
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    • v.33 no.4
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    • pp.229-236
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    • 2009
  • The glycoprotein hormone family represents a class of heterodimers, that includes the placental hormone equine chorionic gonadotropin (eCG) and the anterior pituitary hormones- follitropin (FSH), lutropin (LH), and thyrotropin (TSH). The 4 hormones are heterodimers, with a common $\alpha$-subunit and unique $\beta$-subunits. eCG is the most heavily glycosylated of the known pituitary and placental glycoprotein hormones. Recent observations using single chain glycoprotein hormone analogs in which, the $\beta$-and $\alpha$-subunits are linked, implied that heterodimeric-like quaternary configuration is not a prerequisite for receptor/signal transduction. To study the function and signal transduction of tethered rec-eCG, a single chain eCG molecule was constructed and rec-eCG protein was produced. Molecular mass of the single chain is about 45 kDa. All mice were ovulated by tethered rec-eCG treatment. The dual activity of tethered rec-eCG was determined in receptor cell lines of nonequid species; in fact, this dual activity was proven in species other than horse. Tethered rec-eCG in equids does not bind to FSH receptors, suggesting that eCG is primarily an LH-like hormone in the horse. Taken together, these data suggest that tethered rec-eCG has dual activity in nonequid species in vitro. However, it has only LH-like activity in equid species in vitro.

Low Power Flip-Flop Circuit with a Minimization of Internal Node Transition (인터널 노드 변환을 최소화시킨 저전력 플립플롭 회로)

  • Hyung-gyu Choi;Su-yeon Yun;Soo-youn Kim;Min-kyu Song
    • Transactions on Semiconductor Engineering
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    • v.1 no.1
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    • pp.14-22
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    • 2023
  • This paper presents a low-power flip-flop(FF) circuit that minimizes the transition of internal nodes by using a dual change-sensing method. The proposed dual change-sensing FF(DCSFF) shows the lowest dynamic power consumption among conventional FFs, when there is no input data transition. From the measured results with 65nm CMOS process, the power consumption has been reduced by 98% and 32%, when the data activity is 0% and 100%, respectively, compared to conventional transmission gate FF(TGFF). Further, compared to change-sensing FF(CSFF), the power consumption of proposed DCSFF is smaller by 30%.

The effects of dual-task training on ambulatory abilities of stroke patients: Review of the latest trend

  • Lee, Gyu Chang;Choi, Won Jae
    • Physical Therapy Rehabilitation Science
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    • v.1 no.1
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    • pp.1-5
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    • 2012
  • Objective: Dual-task walking deficits impact functional daily life, which often requires walking while performing simultaneous tasks such as talking, thinking or carrying an object. This study is to find out the latest trend of dual-task training's influence on ambulatory abilities of a stroke patient. Design: Systematic review of randomized controlled trials. Methods: This literature review was conducted in Pubmed and Sciencedirect with the follwing key words:stroke, cerebro-vascular accident, hemiplegia, gait, rehabilitation, exercise. 7 studies were chosen in findings by search tool. 3 studies were case study, 3 studies were cross sectional observational study and 1 study was randomized controlled trial. Results: It was found that stroke patients have difficulties in doing 2 motor tasks simultaneously and when they do 2 tasks, one is done in a naturally preferred activity areas. Moreover, when simply applying dual-tasks, the walking speed decreased. Meanwhile, when applying them through training, the speed increased. This showed the improvement of effective task-implementation abilities after dual-task training using task-integration models. Conclusions: In the beginning of the 2000s, dual-tasks were implemented by simply combining walking and cognition or exercise task, and the results of this study suggest that subjects with stroke have difficulty performing dual task. However, the latest trend is to let patients do the dual-task training by combining it with virtual reality. Therefore, dual task training could be performed in a safe in the environment such as virtual reality or augment reality.

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Effect of Dual Inoculation with Glomus mosseae and Rhizobium meliloti on Growth and Nitrogenase Activity of Medicago sativa L. (Glomus mosseae와 Rhizobium meliloti의 동시접종이 알팔파의 생장 및 질소고정활성에 미치는 영향)

  • 유익동;서현창;김원곤;박동진;조갑연;김창진
    • Microbiology and Biotechnology Letters
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    • v.21 no.2
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    • pp.95-100
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    • 1993
  • Effect of dual inoculation with vesicular-arbuscular(VA) mycorrhizal fungi, Glomus mosseae, and Rhizobium meliloti R455 on growth, nodulation, and nitrogenase activity of alfalfa (Medicago sativa L. cv. Vernal) were examined in pot experiment. After 63 days growth, shoot length, number of leaf, and leaf size of alfalfa were increased as as result of dual inoculation with Glomus mosseae and Rhizobium meliloti. Total dry weight of alfalfa plant was increased 1.4 times compared to single inoculation with Rhizobium meliloti. Nodule number and mean fresh weight of nodule per plant were also increased due to the mycorrhizal infection.

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The effects of Nafion$^{(R)}$ ionomer content in dual catalyst layer on the performances of PEMFC MEAs

  • Kim, Kun-Ho;Jeon, Yoo-Taek
    • 한국신재생에너지학회:학술대회논문집
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    • 2011.05a
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    • pp.95.2-95.2
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    • 2011
  • In order to achieve high performance and low cost for commercial applications, the development of membrane electrode assemblies (MEA), in which the electrochemical reactions actually occur, must be optimized. Expensive platinum is currently used as an electrochemical catalyst due to its high activity. Although various platinum alloys and non-platinum catalysts are under development, their stabilities and catalytic activities, especially in terms of the oxygen reduction (ORR), render them currently unsuitable for practical use. Therefore, it is important to decrease platinum loading by optimizing the catalysts and electrode microstructure. In this study, we prepared several different MEAs (non-uniform Nafion$^{(R)}$ ionomer loading electrode) which have dual catalyst layers to find the optimal Nafion$^{(R)}$ ionomer distribution in the electrodes. We changed Nafion$^{(R)}$ ionomer content in the layers to find the ideal composition of the binder and Pt/C in the electrode. For MEAs with various ionomer contents in the anodes and cathodes, the electrochemical activity (activation overpotential) and the mass transport properties (concentration overpotential) were analyzed and correlated with the single cell performance. The dual catalyst layers MEA showed higher cell performance than uniformly fabricated MEA, especially at the high current density region.

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One-step synthesis of dual-transition metal substitution on ionic liquid based N-doped mesoporous carbon for oxygen reduction reaction

  • Byambasuren, Ulziidelger;Jeon, Yukwon;Altansukh, Dorjgotov;Ji, Yunseong;Shul, Yong-Gun
    • Carbon letters
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    • v.17 no.1
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    • pp.53-64
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    • 2016
  • Nitrogen (N)-doped ordered mesoporous carbons (OMCs) with a dual transition metal system were synthesized as non-Pt catalysts for the ORR. The highly nitrogen doped OMCs were prepared by the precursor of ionic liquid (3-methyl-1-butylpyridine dicyanamide) for N/C species and a mesoporous silica template for the physical structure. Mostly, N-doped carbons are promoted by a single transition metal to improve catalytic activity for ORR in PEMFCs. In this study, our N-doped mesoporous carbons were promoted by the dual transition metals of iron and cobalt (Fe, Co), which were incorporated into the N-doped carbons lattice by subsequently heat treatments. All the prepared carbons were characterized by via transmission electron microscopy (TEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). To evaluate the activities of synthesized doped carbons, linear sweep was recorded in an acidic solution to compare the ORR catalytic activities values for the use in the PEMFC system. The dual transition metal promotion improved the ORR activity compared with the single transition metal promotion, due to the increase in the quaternary nitrogen species from the structural change by the dual metals. The effect of different ratio of the dual metals into the N doped carbon were examined to evaluate the activities of the oxygen reduction reaction.

Elution of amikacin and vancomycin from a calcium sulfate/chitosan bone scaffold

  • Doty, Heather A.;Courtney, Harry S.;Jennings, Jessica A.;Haggard, Warren O.;Bumgardner, Joel D.
    • Biomaterials and Biomechanics in Bioengineering
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    • v.2 no.3
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    • pp.159-172
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    • 2015
  • Treatment of polymicrobial infected musculoskeletal defects continues to be a challenge in orthopaedics. This research investigated single and dual-delivery of two antibiotics, vancomycin and amikacin, targeting different classes of microorganism from a biodegradable calcium sulfate-chitosan-nHA microsphere composite scaffold. The addition of chitosan-nHA was included to provide additional structure for cellular attachment and as a secondary drug-loading device. All scaffolds exhibited an initial burst of antibiotics, but groups containing chitosan reduced the burst for amikacin at 1hr by 50%, and vancomycin by 14-25% over the first 2 days. Extended elution was present in groups containing chitosan; amikacin was above MIC ($2-4{\mu}g/mL$, Pseudomonas aeruginosa) for 7-42 days and vancomycin was above MIC ($0.5-1{\mu}g/mL$ Staphylococcus aureus) for 42 days. The antibiotic activity of the eluates was tested against S. aureus and P. aeruginosa. The elution from the dual-loaded scaffold was most effective against S. aureus (bacteriostatic 34 days and bactericidal 27 days), compared to vancomycin-loaded scaffolds (bacteriostatic and bactericidal 14 days). The dual- and amikacin-loaded scaffolds were effective against P. aeruginosa, but eluates exhibited very short antibacterial properties; only 24 hours bacteriostatic and 1-5 hours bactericidal activity. For all groups, vancomycin recovery was near 100% whereas the amikacin recovery was 41%. In conclusion, in the presence of chitosan-nHA microspheres, the dual-antibiotic loaded scaffold was able to sustain an extended vancomycin elution longer than individually loaded scaffolds. The composite scaffold shows promise as a dual-drug delivery system for infected orthopaedic wounds and overcomes some deficits of other dual-delivery systems by extending the antibiotic release.

A New Reporter Vector System Based on Flow-Cytometry to Detect Promoter Activity

  • Jung, Sun-Do;Choi, Ji-Hye;Hong, Chang-Wan;Lee, Hyun-Ji;Park, Yoon-Kyung;Shin, Jung-Hoon;Park, Jae-Won;Park, Se-Ho
    • IMMUNE NETWORK
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    • v.9 no.6
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    • pp.243-247
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    • 2009
  • In this study, we report the development of a new dual reporter vector system for the analysis of promoter activity. This system employs green fluorescence emitting protein, EGFP, as a reporter, and uses red fluorescence emitting protein, DsRed, as a transfection control in a single vector. The expression of those two proteins can be readily detected via flow cytometry in a single analysis, with no need for any further manipulation after transfection. As this system allows for the simultaneous detection of both the control and reporter proteins in the same cells, only transfected cells which express the control protein, DsRed, can be subjected to promoter activity analysis, via the gating out of all un-transfected cells. This results in a dramatic increase in the promoter activity detection sensitivity. This novel reporter vector system should prove to be a simple and efficient method for the analysis of promoter activity.