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Why a Combination of WP 631 and Epo B is an Improvement on the Drugs Singly - Involvement in the Cell Cycle and Mitotic Slippage

  • Bukowska, Barbara;Rogalska, Aneta;Forma, Ewa;Brys, Magdalena;Marczak, Agnieszka
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.3
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    • pp.1299-1308
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    • 2016
  • Our previous studies clearly demonstrated that a combination of WP 631 and Epo B has higher activity against ovarian cancer cells than either of these compounds used separately. In order to fully understand the exact mechanism of action in combination, we assessed effects on the cell cycle of SKOV-3 cells. We evaluated three control points essential for WP 631 and Epo B action to determine which cell cycle-regulating proteins (CDK1/cyclin B complex, EpCAM or HMGB1) mediate activity. The effects of the drug on the cell cycle were measured based on the nuclear DNA content using flow cytometry. Expression of cell cycle-regulating genes was analyzed using real-time PCR. It was discovered that WP 631, at the tested concentration, did not affect the SKOV-3 cell cycle. Epo B caused significant G2/M arrest, whereas the drug combination induced stronger apoptosis and lower mitotic arrest than Epo B alone. This is very important information from the point of view of the fight against cancer, as, while mitotic arrest in Epo B-treated cells could be overcame after DNA damage repair, apoptosis which occurs after mitotic slippage in combination-treated cells is irreversible. It clearly explains the higher activity of the drug combination in comparison to Epo B alone. Epo B acts via the CDK1/cyclin B complex and has the ability to inhibit CDK1, which may be a promising strategy for ovarian cancer treatment in the future. The drug combination diminishes EpCAM and HMGB1 expression to a greater degree than either WP 631 and Epo B alone. Owing to the fact that the high expression of these two proteins is a poor prognostic factor for ovarian cancer, a decrease in their expression, observed in our studies, may result in improved efficacy of cancer therapy. The presented findings show that the combination of WP 631 and Epo B is a better therapeutic option than either of these drugs alone.

Conventional Radiotherapy with Concurrent Weekly Cisplatin in Locally Advanced Head and Neck Cancers of Squamous Cell Origin - a Single Institution Experience

  • Dimri, Kislay;Pandey, Awadhesh Kumar;Trehan, Romeeta;Rai, Bhavana;Kumar, Anup
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6883-6888
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    • 2013
  • Background: Platinum based concurrent chemo-radiation is the de-facto standard of care in the non-surgical management of locally-advanced head and neck cancer of squamous origin. Three-weekly single agent cisplatin at 100 $mg/m^2$ concurrent with radical radiotherapy has demonstrated consistent improvement in loco-regional control and survival. This improvement is however at the cost of considerable hematologic toxicity and poor overall compliance. The routine use of this regime is improbable in developing countries with limited resources. We therefore aimed to determine the safety and efficacy of an alternative regime of weekly cisplatin and concurrent radiotherapy in such patients. Materials and Methods: January-05 and April-12, 188 patients of locally-advanced head and neck cancer of squamous origin were treated with concurrent weekly-cisplatin at $35mg/m^2$ and conventional radiotherapy 60-66Gy/30-33 fractions/5days per week. Results: Overall, 95% patients received planned doses of RT while 74% completed within the stipulated overall treatment time of <50 days. Eighty-two percent received at-least 5 weekly cycles. Grade-III/IV mucositis was seen in 58%/9% respectively, which resulted in mean weight loss of 9.2% from a pre-treatment mean of 54.5 kg. Grade-III hematologic toxicity-0.5%; grade II nephrotoxicity-2.5% and grade III emesis-3% were also seen. Grade-III/IV subcutaneous toxicity-10%/1% and grade-III/IV xerostomia-10%/0% were observed. Complete responses at the primary site, regional nodes and overall disease were seen in 86%, 89% and 83% patients respectively. The median and 5-years disease-free survival were 26 months and 39.4% respectively, while the median and overall survival were 27 months and 41.8% respectively. Conclusions: Weekly-cisplatin at 35 $mg/m^2$ when delivered concurrently with conventional radical RT (at-least 66y/33 fractions) in locally-advanced head and neck cancer is well tolerated with minimal hematologic and neprologic toxicity and can be routinely delivered on an out-patient basis. It is an effective alternative to the standard 3-weekly cisplatin especially in the context of developing countries.

High-Resolution Seismic Reflection Profiling on Land with Hydrophones Employed in the Stream-Water Driven Trench (하천수유입과 하이드로폰을 이용한 육상 고분해능 탄성파반사법탐사)

  • Kim Ji-Soo;Han Su-Hyung;Kim Hak-Soo;Choi Won-Suk;Jung Chang-Ho
    • Geophysics and Geophysical Exploration
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    • v.4 no.4
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    • pp.133-144
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    • 2001
  • An effective seismic reflection technique for mapping the cavities and bedrock surface in carbonate rocks is described. The high resolution seismic reflection images were successfully registered by using the hydrophones employed in the stream-water driven trench, and were effectively focused by applying optimal data processing sequences. The strategy included enhancement of the signal interfered with the large-amplitude scattering noise, through pre- and post stack processing such as time-variant filtering, bad-trace editing, residual statics, velocity analysis, and careful muting after NMO (normal moveout) correction. The major reflections including the bedrock surface were mapped with the desired resolution and were correlated to the seismic crosshole tomographic data. Shallow major reflectors could be identified and analyzed on the AGC (auto gain control)-applied field records. Three subhorizontal layers were identified with their distinct velocities; overburden (<3000 m/s), sediments (3000-4000 m/s), limestone bedrock (>4000 m/s). Taking into account of no diffraction effects in the field records, gravel-rich overburdens and sediments are considered to be well sorted. Based on the images mapped consistently on the whole survey line and seismic velocity increasing with depth, this area probably lacks in sizable cavities (if any, no air-filled cavities).

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Effect of Banhahoobak-tang (Banxiahoupo-tang) Extract (BHTe) on Psychological Stress (반하후박탕(半夏厚朴湯)이 생쥐의 심리적 스트레스에 미치는 영향과 유전자 분석)

  • Choi, Geum-Ae;Cho, Su-In;Kim, Kyeong-Su;Choi, Chang-Won;Wei, Tung-Shuen;Yang, Seung-Joung;Park, Soo-Yeon;Kim, Kyeong-Ok
    • Journal of Oriental Neuropsychiatry
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    • v.26 no.2
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    • pp.117-130
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    • 2015
  • Objectives: Banhahoobak-tang has been used to treat plum-pit qi, chest and hypochondriac distension, moist or greasy tongue coat, and wiry slow or wiry slippery pulse. It might be used to control coughing and vomiting. We observed that Banhahoobak-tang extract (BHTe) had anti-psychological stress effect. The objective of this study was to determine the effect of BHTe on restoring the transcriptional regulation of genes related to psychological stress. Methods: After giving psychological stress to mice, BHTe was orally administered at 100 mg/kg/day for five days. After extracting whole brain tissue from the mice, the gene expression changes were determined by microarray. Transcription factor binding site (TFBS) analysis showed up- and down-regulated genes related to psychological stress were protected by BHTe and segregated according to the structure of TFBS. We performed text based Pubmed search to select significant target genes involved in psychological stress affected by BHTe. Results: 1. Serum corticosterone level was decreased in the BHTe administered group, although the psychological stress was increased. 2. The BHTe administered group had no significant change in noradrenaline content in brain tissue, but the psychological stress group had decreased level. 3. The BHTe administered group had increased time of staying at open-arm than the psychological stress group. 4. Microarray revealed that TANK and RARA genes were up-regulated genes while AES, CDC42, FOS, NCL, and PVR were down-regulated genes by psychological stress but restored by BHTe.

Noninvasive Monitoring of Bleomycin-induced Lung Injury in Rats Using Pulmonary Function Test

  • Yang, Mi-Jin;Yang, Young-Su;Kim, Yong-Bum;Cho, Kyu-Hyuk;Heo, Jeong-Doo;Lee, Kyu-Hong;Song, Chang-Woo
    • Toxicological Research
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    • v.24 no.4
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    • pp.273-280
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    • 2008
  • The single intratracheal instillation (ITI) of bleomycin (BLM) is a widely used method for inducing experimental pulmonary fibrosis in rat model. In the present study, pulmonary function tests (PFTs) of tidal volume ($V_T$), minute volume ($V_M$), and respiratory frequency ($F_R$) have been applied to study their possibility as a tool to monitor the progress of BLM-induced lung injury in rat model. Rats were treated with a single ITI of BLM (2.5 mg/kg) or saline (control). Animals were euthanized at 3, 7, 14, 21, and 28 days post-ITI. Lung toxicity effects were evaluated by inflammatory cell count, lactate dehydrogenase (LDH) activity in the bronchoalveolar lavage fluid (BALF), and light microscopic examination of lung injury. The PFT parameters were measured immediately before the animals were sacrificed. BLM treatment induced significant cellular changes in BALF-increase in number of total cells, neutrophils, and lymphocytes along with sustained increase in number of macrophages compared to the controls at days 3, 7, and 14. BALF LDH level was significantly increased compared to that in the controls up to day 14. On day 3, infiltration of neutrophils was observed in the alveolar spaces. These changes developed into marked peribronchiolar and interstitial infiltration by inflammatory cells, and extensive thickening of the interalveolar septa on day 7. At 14, 21, and 28 days, mild peribronchiolar fibrosis was observed along with inflammatory cell infiltration. The results of PFT show significant consistencies compared to the results of other toxicity tests. These data demonstrate that the most suitable time point for assessing lung fibrosis in this model is 14 days post-ITI of BLM based on the observation of fibrosis at 14, 21, and 28 days. Further, the progress of lung injury can be traced by monitoring the PFT parameters of $F_R$, $V_T$, and $V_M$.

Studies on the Press Drying and the Chemical Absorption of the Plywood Treated with Diammonium Phosphate (제2인산(第2燐酸)암모늄 처리합판(處理合板)의 약제흡수(藥劑吸收) 및 열판건조(熱板乾燥)에 관(關)한 연구(硏究))

  • Kim, Jong-Man
    • Journal of the Korean Wood Science and Technology
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    • v.23 no.4
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    • pp.39-45
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    • 1995
  • The plywoods commonly used as decorative interior materials for the construction are inflammable and so it is a causative factor for making fire accidents, resulting in the destruction of human life and personal properties. Indeed, it is, therefore, required to produce fire-retardant plywoods. In this study, a special grade of defect-free, Kapur plywood was used. Specimens were cut into 3- by 20cm dimensions from 120- by 240- by 0.33-cm panels(thin panel) or 120- by 240- by 0.5-cm panels(thick panel). Some specimens were treated with diammonium phosphate(DAP), but some were not treated with diammonium phosphate to use as control panels. Chemical absorption, drying curves, drying rates and dynamic Young's modulus were investigated. The results were summaries as follows; 1. The specimens were soaked into 19% diammonium phosphate solution by a full cell pressure process and the diammonium phosphate retained in the thin and thick plywoods was 1.409kg/$(30cm)^3$, 1.487kg/$(30cm)^3$, respectively. 2. Diammonium phosphate-treated plywoods were redried with press-drying process at one of either condition dried on the platen($115^{\circ}C$) for a period of time or dried on the platen($50^{\circ}C$) for 3 hrs plus in a dry-oven($30^{\circ}C$) for 24 hrs. or dried on the platen($60^{\circ}C$) for 2 hrs plus in a dry-oven($30^{\circ}C$) for 24 hrs. The drying rate of treated thin specimens dried at $60^{\circ}C$ plus $30^{\circ}C$ and $115^{\circ}C$ only was found to be 0.04 %/min. and 8.53 %/min. Similarly, the drying rate of treated thick specimens were 0.03 %/min. and 6.77 %/min. respectively. 3. It was evident that highly-significantly different drying rate of treated plywoods was observed between plywood thicknesses and platen temperatures and the rate was increased by elevating the platen temperature up to $115^{\circ}C$. Based on the two-way variance analysis, highly significant drying rate was observed from the interaction between plywood thicknesses and platen temperatures. 4. After redrying, the specimens were weighed and reconditioned to a constant weight in a facility maintained temperature ($20^{\circ}C$) and relative humidity(65%) prior to test dynamic Young's modulus. The test revealed that the thin specimens dried at the platen temperature of $50^{\circ}C$, $60^{\circ}C$, $115^{\circ}C$ and untreated specimens showed 1.070E+09 dyne/$cm^2$, 1.156E+09 dyne/$cm^2$, 1.243E+09 dyne/$cm^2$, and 1.052E+09 dyne/$cm^2$, respectively. Likewise, the thick specimens revealed 5.647E+09 dyne/$cm^2$ 5.670E+09 dyne/$cm^2$, 6.395E+09 dyne/$cm^2$ and 5.415E+09 dyne/$cm^2$, respectively. 5. It was evident that significantly different dynamic Young's modulus was observed between the plywood thickness and the platen temperature, but not in the two-way interaction between the plywood thickness${\times}$the platen temperature.

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System Design for a Urban Energy Monitoring and Visualization Environment Using Ubiquitous Sensor Network and Social Sensor Networking (Ubiquitous Sensor Network 및 Social Sensor Networking을 이용한 도시 에너지 모니터링 가시화 시스템 설계)

  • Choe, Yoon;Jang, Myeong-Ho;Kim, Sung-Ah
    • Journal of the HCI Society of Korea
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    • v.5 no.2
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    • pp.7-14
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    • 2010
  • Urban Data collected through Sensor Network is becoming crucial to understand and analyse a city. Thus, the Ubiquitous Sensor Network builds the foundation of the u-City development. This research aims to develop an energy monitoring application with an intuitive visualization environment which integrates energy usage information on top of urban geospatial information. Such a system will be able to facilitate effective energy supply plan at the early stages of urban planning, and eventually to encourage citizens to conserve energy by giving them real time monitoring information in an easy to understand visual environment. The system provides multiple layers of energy-related information coupled with the geospatial information layer in order to accommodate multiple viewpoints. On the other hand, the system provides logical Level of Detail control based on urban spatial information hierarchy. We defined the system concept and functions, and designed the data structure and the methods of information visualization. This paper presents the visualization methods, data structure, interactions scenarios which combines spacial information, E-GIS data and the energy related sensor data. Furthermore this research tries to introduce the concept of Social Sensor Networking to enhance the monitoring quality.

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Evaluation of Source Identification Method Based on Energy-Weighting Level with Portal Monitoring System Using Plastic Scintillator

  • Lee, Hyun Cheol;Koo, Bon Tack;Choi, Chang Il;Park, Chang Su;Kwon, Jeongwan;Kim, Hong-Suk;Chung, Heejun;Min, Chul Hee
    • Journal of Radiation Protection and Research
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    • v.45 no.3
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    • pp.117-129
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    • 2020
  • Background: Radiation portal monitors (RPMs) involving plastic scintillators installed at the border inspection sites can detect illicit trafficking of radioactive sources in cargo containers within seconds. However, RPMs may generate false alarms because of the naturally occurring radioactive materials. To manage these false alarms, we previously suggested an energy-weighted algorithm that emphasizes the Compton-edge area as an outstanding peak. This study intends to evaluate the identification of radioactive sources using an improved energy-weighted algorithm. Materials and Methods: The algorithm was modified by increasing the energy weighting factor, and different peak combinations of the energy-weighted spectra were tested for source identification. A commercialized RPM system was used to measure the energy-weighted spectra. The RPM comprised two large plastic scintillators with dimensions of 174 × 29 × 7 ㎤ facing each other at a distance of 4.6 m. In addition, the in-house-fabricated signal processing boards were connected to collect the signal converted into a spectrum. Further, the spectra from eight radioactive sources, including special nuclear materials (SNMs), which were set in motion using a linear motion system (LMS) and a cargo truck, were estimated to identify the source identification rate. Results and Discussion: Each energy-weighted spectrum exhibited a specific peak location, although high statistical fluctuation errors could be observed in the spectrum with the increasing source speed. In particular, 137Cs and 60Co in motion were identified completely (100%) at speeds of 5 and 10 km/hr. Further, SNMs, which trigger the RPM alarm, were identified approximately 80% of the time at both the aforementioned speeds. Conclusion: Using the modified energy-weighted algorithm, several characteristics of the energy weighted spectra could be observed when the used sources were in motion and when the geometric efficiency was low. In particular, the discrimination between 60Co and 40K, which triggers false alarms at the primary inspection sites, can be improved using the proposed algorithm.

Polymorphisms in the uncoupling protein 3 gene and their associations with feed efficiency in chickens

  • Jin, Sihua;Yang, Lei;He, Tingting;Fan, Xinfeng;Wang, Yiqiu;Ge, Kai;Geng, Zhaoyu
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.9
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    • pp.1401-1406
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    • 2018
  • Objective: The uncoupling protein 3 (UCP3) is a member of the mitochondrial anion carrier superfamily and has crucial effects on growth and feed efficiency in many species. Therefore, the objective of the present study was to examine the association of polymorphisms in the UCP3 gene with feed efficiency in meat-type chickens. Methods: Six single nucleotide polymorphisms (SNPs) of the UCP3 gene were chosen to be genotyped using matrix-assisted laser desorption-ionization time-of-flight mass spectrometry in meat-type chicken populations with 724 birds in total. Body weight at 49 (BW49) and 70 days of age (BW70) and feed intake (FI) in the interval were collected, then body weight gain (BWG) and feed conversion ratio (FCR) were calculated individually. Results: One SNP with a low minor allele frequency (<1%) was removed by quality control and data filtering. The results showed that rs13997809 of UCP3 was significantly associated with BWG and FCR (p<0.05), and that rs13997811 had significant effects on BW70 and BWG (p<0.05). Rs13997812 of UCP3 was strongly associated with BW70, FI, and FCR (p<0.05). Furthermore, individuals with AA genotype of rs13997809 had significantly higher BWG and lower FCR (p<0.05) than those with AT genotype. The GG individuals showed strongly higher BW70 and BWG than AA birds in rs13997811 (p<0.05). Birds with the TT genotype of rs13997812 had significantly greater BW70 and lower FCR compared with the CT birds (p<0.05). In addition, the TAC haplotype based on rs13997809, rs13997811, and rs13997812 showed significant effects on BW70, FI, and FCR (p<0.05). Conclusion: Our results therefore demonstrate important roles for UCP3 polymorphisms in growth and feed efficiency that might be used in meat-type chicken breeding programs.

Anti-Proliferation Effects and Molecular Mechanisms of Action of Tetramethypyrazine on Human SGC-7901 Gastric Carcinoma Cells

  • Ji, Ai-Jun;Liu, Sheng-Lin;Ju, Wen-Zheng;Huang, Xin-En
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3581-3586
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    • 2014
  • Aim: To investigate the effects of tetramethypyrazine (TMP) on proliferation and apoptosis of the human gastric carcinoma cell line 7901 and its possible mechanism of action. Methods: The viability of TMP-treated 7901 cells was measured with a 3-(4, 5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT) and cell apoptosis was analyzed by flow cytometry. The distribution of cells in different phases of cell cycle after exposure of TMPs was analyzed with flow cytometry. To investigate the molecular mechanisms of TMP-mediated apoptosis, the expression of NF-${\kappa}Bp65$, cyclinD1 and p16 in SGC-7901 cells was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. Results: TMP inhibited the proliferation of human gastric carcinoma cell line 7901 in dose and time dependent manners. Cell growth was suppressed by TMP at different concentrations (0.25, 0.5, 1.0, 2.0 mg/ml), the inhibition rate is 0.46%, 4.36%, 14.8%, 76.1% (48h) and 15.5%, 18.5%, 41.2%, 89.8% (72h) respectively. When the concentration of TMPs was 2.0mg/ml, G1-phase arrest in the SGC-7901 cells was significant based on the data for cell cycle distribution. RT-PCR demonstrated that NF-${\kappa}Bp65$ and cyclin D1 mRNA expression was significantly down-regulated in 7901 cells treated with 2.0 mg/ml TMP for 72h (p<0.05), while the p16 mRNA level was up-regulated (p<0.05). The protein expression of NF-${\kappa}Bp65$ and cyclin D1 decreased gradually with the increase in TMP concentration, compared with control cells (p<0.05), while expression of protein p16 was up-regulated (p<0.01). Conclusion: TMP exhibits significant anti-proliferative and pro-apoptotic effects on the human gastric carcinoma cell line SGC-7901. NF-${\kappa}Bp65$, cyclinD1 and p16 may also play important roles in the regulation mechanisms.