Search results for: bloodstream expression site

Authors: Seok Woo Chang

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Aim: Capseal I and Capseal II are calcium silicate and calcium phosphate based experimental root canal sealer. The aim of this study was to evaluate the biocompatibility and mineralization potential of Capseal I and Capseal II. Materials and Methods: The biocompatibility and mineralization-related gene expression (alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OCN)) of Capseal I and Capseal II were compared using methylthiazol tetrazolium assay and reverse transcription-polymerization chain reaction analysis, respectively. The results were analyzed by Kruskal-Wallis test. P-value of < 0.05 was considered significant. Result: Both Capseal I and Capseal II were favorable in biocompatibility and influenced the messenger RNA expression of ALP and BSP. Conclusion: Within the limitation of this study, Capseal is biocompatible and have mineralization promoting potential, and thus could be a promising root canal sealer.

Keywords: biocompatibility, mineralization-related gene expression, Capseal I, Capseal II

Procedia PDF Downloads 281

Authors: F. Polito, M. Cucinotta, A. Conti, C. Lo Giudice, C. Tomasello, F. Angileri, D. La Torre, M. Aguennouz

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Glioblastoma multiforme (GBM) is the most aggressive form of brain tumors, with an extremely poor prognosis. Telomeres lenght is associated with tumor progression in several type of human cancers and telomere elongation is a common molecular feature of advanced malignancies. Among the telomeric shelterin proteins PTOP is required for telomeric protein complex assembly, telomerase recruitment and activity, and telomere length regulation through a PTOP-telomerase interaction. Previous studies suggest that PTOP upregulation is involved in radioresistance and telomere lengthening in colorectal cancer cells. Moreover, in human osteosarcoma cells PTOP deletion led to telomere shortening, increased apoptosis and radiation sensitivity enhancement. However, to date, little is known about the role of PTOP in progression of glioma cancers. In light of this background aim of the study is to investigate the expression of PTOP in different grades of human glioma and its correlation with the pathological grade of gliomas, grades of malignancy, proliferative activity and apoptosis. Fifteen Low Grade Astrocytomas (LGA), 18 Anaplastic Astrocytomas (AA) and 26 Glioblastoma Multiforme (GBM) samples were analyzed. Three samples of normal brain tissue (NBT) were used as controls. The expression levels of PTOP, h-TERT, BIRC1 and cyclin D1 were determined by real time PCR and/or western blot. Results obtained shows that PTOP expression in glioma tissues is tightly correlated with clinical grade ( p < 0.01 ). No correlation was found between PTOP expression and other clinicopathologic parameters. The expression of PTOP was positively correlated with the expression of hTERT and TERF1. Furthermore PTOP positively correlates with cyclin D1 and negatively correlates with the expression of BIRC1. Our findings indicate that PTOP might play key role in the progression of glioma regulating telomerase activity and likely through regulation of cell cycle and apoptosis. In conclusion results obtained prompted us to speculate that PTOP might represents a potential molecular bio marker and a therapeutic target for the treatment of glioblastoma tumors.

Keywords: glioblastoma, PTOP, telomere, brain tumors

Procedia PDF Downloads 346

Authors: Amin Pashaye Amiri

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Freedom of information, according to which the public has a right to have access to government-held information, is largely considered as a tool for improving transparency and accountability in governments, and as a requirement of self-governance and good governance. So far, more than ninety countries have recognized citizens’ right to have access to public information. This recognition often took place through the adoption of an act referred to as “freedom of information act”, “access to public records act”, and so on. A freedom of information act typically imposes a positive obligation on a government to initially and regularly release certain public information, and also obliges it to provide individuals with information they request. Such an act usually allows governmental bodies to withhold information only when it falls within a limited number of exemptions enumerated in the act such as exemptions for protecting privacy of individuals and protecting national security. Some steps have been taken at the national and international level towards the recognition of freedom of information as a human right. Freedom of information was recognized in a few countries as a part of freedom of expression, and therefore, as a human right. Freedom of information was also recognized by some international bodies as a human right. The Inter-American Court of Human Rights ruled in 2006 that Article 13 of the American Convention on Human Rights, which concerns the human right to freedom of expression, protects the right of all people to request access to government information. The European Court of Human Rights has recently taken a considerable step towards recognizing freedom of information as a human right. However, in spite of the measures that have been taken, public access to government information is not yet widely accepted as an international human right. The paper will consider the degree to which freedom of information has been recognized as a human right, and study the possibility of widespread recognition of such a human right in the future. It will also examine the possible benefits of such recognition for the development of the human right to free expression.

Keywords: freedom of information, freedom of expression, human rights, government information

Procedia PDF Downloads 550

Authors: Hsiu-Tsu Cho

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Collective efficacy refers to a group’s sense of its capacity to complete a task successfully or to reach objectives. Little effort has been expended on investigating the relationship between the emotion expression of a leader and collective efficacy. In this study, we examined the impact of the different emotions and emotion expression of a group leader on collective efficacy and explored whether the emotion–expressive effects differed under conditions of negative and positive emotions. A total of 240 undergraduate and graduate students recruited using Facebook and posters at a university participated in this research. The participants were separated randomly into 80 groups of four persons consisting of three participants and a confederate. They were randomly assigned to one of five conditions in a 2 (pride vs. guilt) × 2 (emotion expression of group leader vs. no emotion expression of group leader) factorial design and a control condition. Each four-person group was instructed to get the reward in a group competition of solving the five-disk Tower of Hanoi puzzle and making decisions on an investment case. We surveyed the participants by employing the emotional measure revised from previous researchers and collective efficacy questionnaire on a 5-point scale. To induce an emotion of pride (or guilt), the experimenter announced whether the group performance was good enough to have a chance of getting the reward (ranking the top or bottom 20% among all groups) after group task. The leader (confederate) could either express or not express a feeling of pride (or guilt) following the instruction according to the assigned condition. To check manipulation of emotion, we added a control condition under which the experimenter revealed no results regarding group performance in maintaining a neutral emotion. One-way ANOVAs and post hoc pairwise comparisons among the three emotion conditions (pride, guilt, and control condition) involved assigning pride and guilt scores (pride: F(1,75) = 32.41, p < .001; guilt: F(1,75) = 6.75, p < .05). The results indicated that manipulations of emotion were successful. A two-way between-measures ANOVA was conducted to examine the predictions of the main effects of emotion types and emotion expression as well as the interaction effect of these two variables on collective efficacy. The experimental findings suggest that pride did not affect collective efficacy (F(1,60) = 1.90, ns.) more than guilt did and that the group leader did not motivate collective efficacy regardless of whether he or she expressed emotion (F(1,60) = .89, ns.). However, the interaction effect of emotion types and emotion expression was statistically significant (F(1,60) = 4.27, p < .05, ω2 = .066); the effects accounted for 6.6% of the variance. Additional results revealed that, under the pride condition, the leader enhanced group efficacy when expressing emotion, whereas, under the guilt condition, an expression of emotion could reduce collective efficacy. Overall, these findings challenge the assumption that the effect of expression emotion are the same on all emotions and suggest that a leader should be cautious when expressing negative emotions toward a group to avoid reducing group effectiveness.

Keywords: collective efficacy, group leader, emotion expression, pride, guilty

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Authors: Sekou Kangoye, Alexis Todoskoff, Mihaela Barreau

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Modified Condition/Decision Coverage (MC/DC) is a structural coverage criterion that aims to prove that all conditions involved in a Boolean expression can influence the result of that expression. In the context of automotive, MC/DC is highly recommended and even required for most security and safety applications testing. However, due to complex Boolean expressions that often embedded in those applications, generating a set of MC/DC compliant test cases for any of these expressions is a nontrivial task and can be time consuming for testers. In this paper we present an approach to automatically generate MC/DC test cases for any Boolean expression. We introduce novel techniques, essentially based on binary trees to quickly and optimally generate MC/DC test cases for the expressions. Thus, the approach can be used to reduce the manual testing effort of testers.

Keywords: binary trees, MC/DC, test case generation, nontrivial task

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Authors: Laura Kahn, Paul Rodrigues, Onur Savas, Shannon Hahn

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An empirical understanding of an individual's personality expression can have a profound impact on organizations seeking to strengthen team performance and improve employee retention. A team's personality composition can impact overall performance. Creating a tiered information framework that leverages proxies for a user's social context and lexical and linguistic content provides insight into location-specific personality expression. We leverage the layered framework to examine domain-specific, psychological, and lexical cues within social media posts. We apply DistilBERT natural language transfer learning models with real world data to examine the relationship between Big Five personality expressions of people in Science, Technology, Engineering and Math (STEM) fields.

Keywords: big five, personality expression, social media analysis, workforce development

Procedia PDF Downloads 139

Authors: Jin Hwan Cheong, Mina Hwang, Myung Hoon Han, Je Il Ryu, Young ha Oh, Seong Ho Koh, Wu Duck Won, Byung Jin Ha

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Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) has been reported to play critical roles in the proliferation of various cancer cells. However, the roles of LGR5 in brain tumors and the specific intracellular signaling proteins directly associated with it remain unknown. Expression of LGR5 was first measured in normal brain tissue, meningioma, and pituitary adenoma of humans. To identify the downstream signaling pathways of LGR5, siRNA-mediated knockdown of LGR5 was performed in SH-SY5Y neuroblastoma cells followed by proteomics analysis with 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE). In addition, the expression of LGR5-associated proteins was evaluated in LGR5-inꠓhibited neuroblastoma cells and in human normal brain, meningioma, and pituitary adenoma tissue. Proteomics analysis showed 12 protein spots were significantly different in expression level (more than two-fold change) and subsequently identified by peptide mass fingerprinting. A protein association network was constructed from the 12 identified proteins altered by LGR5 knockdown. Direct and indirect interactions were identified among the 12 proteins. HSP 90-beta was one of the proteins whose expression was altered by LGR5 knockdown. Likewise, we observed decreased expression of proteins in the hnRNP subfamily following LGR5 knockdown. In addition, we have for the first time identified significantly higher hnRNP family expression in meningioma and pituitary adenoma compared to normal brain tissue. Taken together, LGR5 and its downstream sigꠓnaling play critical roles in neuroblastoma and brain tumors such as meningioma and pituitary adenoma.

Keywords: LGR5, neuroblastoma, meningioma, pituitary adenoma, hnRNP

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Authors: Merry Meryam Martgrita, Marselina Irasonia Tan

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One of several aggresive cancer is cancer that overexpress c-erbB2 receptor along with the expression of estrogen receptor. Components of extracellular matrix play an important role to increase cancer cells proliferation, migration and invasion. Both components can affect cancer development by regulating the signal transduction pathways in cancer cells. In recent research, SKOV-3 ovarian cancer cell line, that overexpress c-erbB2 receptor was cultured on type IV collagen and treated with estradiol-17β, to reveal the role of both components on RNA and protein level of c-erbB2 receptor. In this research we found a modulation phenomena of increasing and decreasing of c-erbB2 RNA level and a stabilisation phenomena of c-erbB2 protein expression due to estradiol-17β and type IV collagen. It seemed that estradiol-17β has an important role to increase c-erbB2 transcription and the stability of c-erbB2 protein expression. Type IV collagen has an opposite role. It blocked c-erbB2 transcription when it bound to integrin receptor in SKOV-3 cells.

Keywords: c-erbB2, estradiol-17β, SKOV-3, type IV collagen

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Authors: Giovanni Forte, Melania De Falco, Antonio Santo

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On 24th August 2016, central Italy was affected by a Mw 6.0 earthquake, representing the main shock of a long seismic sequence, which had a second shock Mw 6.6 on 26th October and lasts still nowadays. After the event, several field survey were carried out in the affected areas, which is made of historical masonry buildings. The post event reconnaissance missions were aimed at collecting information on the damage states of the buildings, the triggering of the landslides and the relationships with site effects. In this paper, the data collected after the event are analyzed considering the role of the geological and geomorphological setting and the ground motion scenario. The buildings displayed an uneven damage distribution, which was affected by both topographic and stratigraphic amplification. As pertains the landslides, which were the most recurrent among the ground failures, consisted mainly of rock falls and subordinately of translational slides. Finally, the collected knowledge showed a strong contribution of the local geological and geomorphological site condition on the resulting damage.

Keywords: Amatrice earthquake, damage states, landslides, site effects

Procedia PDF Downloads 324

Authors: Xuan Li, Xiaobing Cui, Nan Meng, Shuangshuang Guo, Lingling Wang

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Objective: To investigate the influence of Paeonol on diabetic nephropathy progression in streptozocin (STZ) -induced diabetic rats. Method Male Wistar rats were injected STZ 30mg.kg-1 combined with Freund's complete adjuvant (CFA) 0.1mL/rat once a week for three weeks. The diabetic rats were treated with Paenol for 13 weeks. At the end of the experiments, the rats were anesthetized. Serum and the kidney were collected. Serum superoxide dismutase (SOD) activity, malondialdehyde (MDA), blood urea nitrogen (BUN), creatinine (Cr) and total cholesterol (Chol) level were detected; kidney paraffin sections were prepared and HE and PAS staining sections were used to evaluate the pathology changes of the kidney. Immunohistochemical analysis was used to observe the expression of VEGF and fibernectin expression in the kidney. Result The blood glucose level remained over 16mmol. L-1 for 13 weeks and the ECM accumulated in the diabetic kidney apparently. Paeonol treatment increased serum SOD activity, however, MDA, BUN, Cr, and Chol level was decreased by paeonol treatment. VEGF and fibernectin expression were increased significantly in the DN rats and paeonol treatment ameliorated the overexpression. Conclusion: paeonol prevented the progression of DN.

Keywords: paeonol, STZ, diabetic nephropathy, fibernectin expression, kidney paraffin sections

Procedia PDF Downloads 463

Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

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Background: Breast cancer occupies the first place among the cancer in women in the world. It is urgent today to study the role of molecular markers which are capable of predicting the dynamics and outcome of the disease. The aim of this study is to define the prognostic value of the content of estrogen receptor (ER), progesterone receptor (PgR), and amplification of HER-2 / neu oncoprotein by studying 3 and 5-year overall and relapse-free survival in 470 patients with primary operable and 280 patients with locally–advanced breast cancer. Materials and methods: Study results of 3 and 5-year overall and relapse-free survival, depending on the content of RE, PgR in primary operable patients showed that ER positive (+) and PgR (+) survival was 100 (96.2%) and 97.3 (94.6%), for ER negative (-) and PgR (-) - 69.2 (60.3%) and 65.4 (57.7%), for ER positive (+) and negative PgR (-) 87.4 (80.1%) and 81.5 (79.3%), for ER negative (-) and positive PgR (+) - 97.4 (93.4%) and 90.4 (88.5%), respectively. Survival results depended also on the level of HER-2 / neu expression. In patients with HER-2 / neu negative the survival rates were as follows: 98.6 (94.7%) and 96.2 (92.3%). In group of patients with the level of HER-2 / neu (2+) expression these figures were: 45.3 (44.3%) and 45.1 (40.2%), and in group of patients with the level of HER-2 / neu (3+) expression - 41.2 (33.1%) and 34.3 (29.4%). The combination of ER negative (-), PgR (-), HER-2 / neu (-) they were 27.2 (25.4%) and 19.5 (15.3%), respectively. In patients with locally-advanced breast cancer the results of 3 and 5-year OS and RFS for ER (+) and PgR (+) were 76.3 (69.3%) and 62.2 (61.4%), for ER (-) and RP (-) 29.1 (23.7%) and 18.3 (12.6%), for ER (+) and PgR (-) 61.2 (47.2%) and 39.4 (25.6%), for ER (-) and PgR (+) 54.3 (43.1%) and 41.3 (18.3%), respectively. The level of HER-2 / neu expression also affected the survival results. Therefore, in HER-2/ neu negative patients the survival rate was 74.1 (67.6%) and 65.1 (57.3%), with the level of expression (2+) 20.4 (14.2%) and 8.6 (6.4%), with the level of expression (3+) 6.2 (3.1%) and 1.2 (1.5%), respectively. The combination for ER, PgR, HER-2 / neu negative was 22.1 (14.3%) and 8.4 (1.2%). Conclusion: Thus, the presence of steroid hormone receptors in breast tumor tissues at primary operable and locally- advanced process as the lack of HER-2/neu oncoprotein correlates with the highest rates of 3- and 5-year overall and relapse-free survival. The absence of steroid hormone receptors as well as of HER-2/neu overexpression in malignant breast tissues significantly degrades the 3- and 5-year overall and relapse-free survival. Tumors with ER, PgR and HER-2/neu negative have the most unfavorable prognostics.

Keywords: breast cancer, estrogen receptor, oncoprotein, progesterone receptor

Procedia PDF Downloads 193

Authors: Suzan Salem, Heba Moustafa, Abd El-Aziz Abd El-Aal

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Seismic micro hazard zonation for urban areas is the first step towards a seismic risk analysis and mitigation strategy. Essential here is to obtain a proper understanding of the local subsurface conditions and to evaluate ground-shaking effects. In the present study, an attempt has been made to evaluate the seismic hazard considering local site effects by carrying out detailed geotechnical and geophysical site characterization in El-Fayoum New City. Seismic hazard analysis and microzonation of El-Fayoum New City are addressed in three parts: in the first part, estimation of seismic hazard is done using seismotectonic and geological information. The second part deals with site characterization using geotechnical and shallow geophysical techniques. In the last part, local site effects are assessed by carrying out one-dimensional (1-D) ground response analysis using the equivalent linear method by program SHAKE 2000. Finally, microzonation maps have been prepared. The detailed methodology, along with experimental details, collected data, results and maps are presented in this paper.

Keywords: El-Fayoum, microzonation, seismotectonic, Egypt

Procedia PDF Downloads 383

Authors: Arzu Baloglu, Ugur Kaplancali

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This paper focuses on Background Check Systems and Pre-Employment Screening. In our study, we attempted to make an online background checking site that will help employers when hiring employees. Our site has two types of users which are free and powered user. Free users are the employees and powered users are the employers which will hire employers. The database of the site will contain all the information about the employees and employers which are registered in the system so the employers can make a search based on their searching criteria to find the suitable employee for the job. The web site also has a comments and points system. The current employer can make comments to his/her employees and can also give them points. The comments will be shown on employee’s profile, so; when an employer searches for an employee he/she can check the points and comments of the employee to see whether he or she is capable of the job or not. The employers can also follow some employees if they desire. This paper has been designed and implemented with using ASP.NET, C# and JavaScript. The outputs have a user friendly interface. The interface also aimed to provide the useful information for Turkish Technology Companies.

Keywords: background, checking, verification, human resources, online

Procedia PDF Downloads 198

Authors: Priyanka Tamta, Sukanya Sharma

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The Kamakhya Temple in Assam plays a very important role in the development of Assam as not only a historical place but also as an archaeologically important site. Temple building activity on the site began in 5th century AD when a cave temple dedicated to Lord Balabhadraswami was constructed here by King Maharajadhiraja Sri Surendra Varman. In the history of Assam, the name of this king is not found and neither the name of this form of Vishnu is known in this region. But this inscription sanctified the place as it recorded the first ever temple building activity in this region. The fifteen hundred years habitation history of the Kamakhya temple sites shows a gradual progression of the site from a religious site to an archaeological site and finally as a historical landmark. Here, in this paper, our main objective is to understand the evolution of Kamakhya temple site as a historical landscape and as an important landmark in the history of Assam. The central theme of the paper is the gradual development of the religious site to a historical landmark. From epigraphical records, it is known that the site received patronage from all ruling dynasties of Assam and its adjoining regions. Royal households of Kashmir, Nepal, Bengal, Orissa, Bihar, etc. have left their footprints on the site. According to records they donated wealth, constructed or renovated temples and participated in the overall maintenance of the deity. This made Kamakhya temple a ground of interaction of faiths, communities, and royalties of the region. Since the 5th century AD, there was a continuous struggle between different beliefs, faiths, and power on the site to become the dominant authority of the site. In the process, powerful beliefs system subsumed minor ones into a larger doctrine of beliefs. This can be seen in the case of the evolution of the Kamakhya temple site as one of the important Shakta temples in India. Today, it is cultural identity marker of the state of Assam within which it is located. Its diverse faiths and beliefs have been appropriated by powerful legends to the dominant faith of the land. The temple has evolved from a cave temple to a complex of seventeen temples. The faith has evolved from the worship of water, an element of nature to the worship of the ten different forms of the goddess with their five male consorts or Bhairavas. Today, it represents and symbolizes the relationship of power and control out of which it has emerged. During different periods of occupation certain architectural and iconographical characters developed which indicated diffusion and cultural adaptation. Using this as sources and the epigraphical records this paper will analyze the interactive and dynamic processes which operated in the building of this cultural marker, the archaeological site of Kamakhya.

Keywords: cultural adaptation and diffusion, cultural and historical landscape, Kamakhya, Saktism, temple art and architecture, historiography

Procedia PDF Downloads 251

Authors: Amtul Jamil Sami

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Apis mellifera is an insect of immense economic importance lives on rich carbohydrate diet including cellulose, nectar, honey and pollen. The carbohydrate metabolism in A mellifera has not been understood fully, as there are no data available, on the functional expression of cellulase gene. The cellulose hydrolyzing enzyme is required for the digestion of pollen cellulose wall, to release the important nutrients (amino acids, minerals, vitamins etc.) from the pollen. A dissection of Apis genome had revealed that there is one gene present for the expression of endo-beta-1,4-glucanase, for cellulose hydrolysis. In the presented work, functional expression of endo-beta-1,4 glucanase gene is reported. Total soluble proteins of the honey bee were isolated and were tested cellulose hydrolyzing enzyme activity, using carboxy-methyl cellulose, as a substrate. A mellifera proteins were able to hydrolyze carboxy-methyl cellulose, confirming its endo- type mode of action. Endo beta-1,4 glucanase enzyme was only present in the gut tissues, no activity was detected in the salivary glands. The pH optima of the enzyme were in the acidic pH range of 4-5-5-0, indicating its metabolic role in the acidic stomach of A mellifera. The reported enzyme is unique, as endo-beta- 1,4 glucanase was able to generate non reducing sugar, as an end product. The results presented, are supportive to the information that the honey bee is capable of producing its novel endo-beta-1,4 glucanase. Further it could be helpful, in understanding, the carbohydrate metabolism in A mellifera.

Keywords: honey bees, Endo-beta 1, 4- glucanase, Apis mellifera, functional expression

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Authors: Hyun Lim, Dong Sook Min, Han Eul Yun, Kil Tae Kim, Ya Nan Sun, Young Ho Kim, Hyun Pyo Kim

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Matrix metalloproteinase (MMP)-13 has an important role for degrading cartilage materials under inflammatory conditions such as arthritis. Since the 70% ethanol extract of Acanthopanax koreanum inhibited MMP-13 expression in IL-1β-treated human chondrocyte cell line, SW1353, two major constituents including acanthoic acid and impressic acid were initially isolated from the same plant materials and their MMP-13 down-regulating capacity was examined. In IL-1β-treated SW1353 cells, acanthoic acid and impressic acid significantly and concentration-dependently inhibited MMP-13 expression at 10 – 100 μM and 0.5 – 10 μM, respectively. The potent one, impressic acid, was found to inhibit MMP-13 expression by blocking the phosphorylation of signal transducer and activator of transcription-1/-2 (STAT-1/-2) and activation of c-Jun and c-Fos among cellular signaling pathway involved, but did not affect the activation of mitogen-activated protein kinases (MAPKs) and nuclear transcription factor-κB (NF-κB). Further, impressic acid was also found to inhibit the expression of MMP-13 mRNA (47.7% inhibition at 10 μM), the glycosaminoglycan release (42.2% reduction at 10 μM) and proteoglycan loss in IL-1-treated rabbit cartilage explants culture. For a further study, 21 impressic acid derivatives were isolated from the same plant materials and their suppressive activities against MMP-13 expression were examined. Among the derivatives, 3α-hydroxy-lup-20(29)-en-23-oxo,28-oic acid, (20R)-3α-hydroxy-29-dimethoxylupan-23,28-dioic acid, acankoreoside F and acantrifoside A clearly down-regulated MMP-13 expression, but impressic acid being most potent. All these results suggest that impressic acid, 3α-hydroxy-lup-20(29)-en-23-oxo,28-oic acid, (20R)-3α-hydroxy-29-dimethoxylupan-23,28-dioic acid, acankoreoside F, acantrifoside A and A. koreanum may have a potential for therapeutic agents to prevent cartilage degradation possibly by inhibiting matrix protein degradation.

Keywords: acanthoic acid, Acanthopanax koreanum, cartilage, impressic acid, matrix metalloproteinase

Procedia PDF Downloads 364

Authors: Yen-Hao Su, Wan-Chun Tang, Ya-Wen Cheng, Peik Sia, Chi-Chen Huang, Yi-Chao Lee, Hsin-Yi Jiang, Ming-Heng Wu, I-Lu Lai, Jun-Wei Lee, Kuen-Haur Lee

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There is a wide range of drugs and combinations under investigation and/or approved over the last decade to treat colorectal cancer (CRC), but the 5-year survival rate remains poor at stages II–IV. Therefore, new, more efficient drugs still need to be developed that will hopefully be included in first-line therapy or overcome resistance when it appears, as part of second- or third-line treatments in the near future. In this study, we revealed that heat shock protein 90 (Hsp90) inhibitors have high therapeutic potential in CRC according to combinative analysis of NCBI's Gene Expression Omnibus (GEO) repository and chemical genomic database of Connectivity Map (CMap). We found that second generation Hsp90 inhibitor, NVP-AUY922, significantly down regulated the activities of a broad spectrum of kinases involved in regulating cell growth arrest and death of NVPAUY922-sensitive CRC cells. To overcome NVP-AUY922-induced upregulation of survivin expression which causes drug insensitivity, we found that combining berberine (BBR), a herbal medicine with potency in inhibiting survivin expression, with NVP-AUY922 resulted in synergistic antiproliferative effects for NVP-AUY922-sensitive and -insensitive CRC cells. Furthermore, we demonstrated that treatment of NVP-AUY922-insensitive CRC cells with the combination of NVP-AUY922 and BBR caused cell growth arrest through inhibiting CDK4 expression and induction of microRNA-296-5p (miR-296-5p)-mediated suppression of Pin1–β-catenin–cyclin D1 signaling pathway. Finally, we found that the expression level of Hsp90 in tumor tissues of CRC was positively correlated with CDK4 and Pin1 expression levels. Taken together, these results indicate that combination of NVP-AUY922 and BBR therapy can inhibit multiple oncogenic signaling pathways of CRC.

Keywords: berberine, colorectal cancer, connectivity map, heat shock protein 90 inhibitor

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Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang

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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.

Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1

Procedia PDF Downloads 247

Authors: Sherif A. Abu El-Magd, Ahmed M. Sefelnasr, Ahmed M. Masoud

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Groundwater modeling is the way and tool for assessing and managing groundwater resources efficiently. The present work was carried out in the ancient Egyptian archeological site (Abydos) fromDynastyIandII.Theareaislocated about 13km west of the River Nilecourse, Upper Egypt. The main problem in this context is that the ground water level rise threatens and damages fragile carvings and paintings of the ancient buildings. The main objective of the present work is to identify the sources of the groundwater recharge in the site, further more, equally important there is to control the ground water level rise. Numerical modeling combined with field water level measurements was implemented to understand the ground water recharge sources. However, building a conceptual model was an important step in the groundwater modeling to phase to satisfy the modeling objectives. Therefore, boreholes, crosssections, and a high-resolution digital elevation model were used to construct the conceptual model. To understand the hydrological system in the site, the model was run under both steady state and transient conditions. Then, the model was calibrated agains the observation of the water level measurements. Finally, the results based on the modeling indicated that the groundwater recharge is originating from an indirect flow path mainly from the southeast. Besides, there is a hydraulic connection between the surface water and groundwater in the study site. The decision-makers and archeologyists could consider the present work to understand the behavior of groundwater recharge and water table level rise.

Keywords: numerical modeling, archeological site, groundwater recharge, egypt

Procedia PDF Downloads 124

Authors: Christian H. Sanabria-Montaña, Rodrigo Huerta-Quintanilla

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A lattice network is a special type of network in which all nodes have the same number of links, and its boundary conditions are periodic. The most basic lattice network is the ring, a one-dimensional network with periodic border conditions. In contrast, the Cartesian product of d rings forms a d-dimensional lattice network. An analytical expression currently exists for the clustering coefficient in this type of network, but the theoretical value is valid only up to certain connectivity value; in other words, the analytical expression is incomplete. Here we obtain analytically the clustering coefficient expression in d-dimensional lattice networks for any link density. Our analytical results show that the clustering coefficient for a lattice network with density of links that tend to 1, leads to the value of the clustering coefficient of a fully connected network. We developed a model on criminology in which the generalized clustering coefficient expression is applied. The model states that delinquents learn the know-how of crime business by sharing knowledge, directly or indirectly, with their friends of the gang. This generalization shed light on the network properties, which is important to develop new models in different fields where network structure plays an important role in the system dynamic, such as criminology, evolutionary game theory, econophysics, among others.

Keywords: clustering coefficient, criminology, generalized, regular network d-dimensional

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Authors: Nadine Wiesmann, Melanie Viel, Christoph Buhr, Rachel Tanner, Wolfgang Tremel, Juergen Brieger

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Recidivation of tumors and the development of resistances against the classical anti-tumor approaches represent a major challenge we face when treating cancer. In order to master this challenge, we are in desperate need of new treatment options beyond the beaten tracks. Zinc oxide nanoparticles (ZnO NPs) represent such an innovative approach. Zinc oxide is characterized by a high level of biocompatibility, concurrently ZnO NPs are able to exert anti-tumor effects. By concentration of the nanoparticles at the tumor site, tumor cells can specifically be exposed to the nanoparticles while low zinc concentrations at off-target sites are tolerated well and can be excreted easily. We evaluated the toxicity of ZnO NPs in vitro with the help of immortalized tumor cell lines and primary cells stemming from healthy tissue. Additionally, the Chorioallantoic Membrane Assay (CAM Assay) was employed to gain insights into the in vivo behavior of the nanoparticles. We could show that ZnO NPs interact with tumor cells as nanoparticulate matter. Furthermore, the extensive release of zinc ions from the nanoparticles nearby and within the tumor cells results in overload with zinc. Beyond that, ZnO NPs were found to further the generation of reactive oxygen species (ROS). We were able to show that tumor cells were more prone to the toxic effects of ZnO NPs at intermediate concentrations compared to fibroblasts. With the help of ZnO NPs covered by a silica shell in which FITC dye was incorporated, we were able to track ZnO NPs within tumor cells as well as within a whole organism in the CAM assay after injection into the bloodstream. Depending on the applied concentrations, selective tumor cell killing seems feasible. Furthermore, the combinational treatment of tumor cells with radiotherapy and ZnO NPs shows promising results. Still, further investigations are needed to gain a better understanding of the interaction between ZnO NPs and the human body to be able to pave the way for their application as an innovative anti-tumor agent in the clinics.

Keywords: metal oxide nanoparticles, nanomedicine, overcome resistances against classical treatment options, zinc oxide nanoparticles

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Authors: Zainul A. Khan, Malik Z. Abdin, Jawaid A. Khan

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Begomoviruses belonging to the family Geminiviridae, have single-stranded circular DNA genomes that are monopartite or bipartite. The large intergenic region (LIR) of the monopartite and common region (CR) of bipartite begomoviruses possess promoter activity in their genomes. In this study, we have characterized novel bidirectional promoters from Cotton leaf curl Burewala virus (CLCuBuV) genome using high-throughput software and analyzed with PlantCARE, PLACE, Cister and PlantPAN databases. The promoters (Rep and CP promoters) were assayed both in stable and transient expression systems in tobacco as well as cotton plants. Rep and CP-based promoters from the LIR sequence of CLCuBuV and 35S promoter of Cauliflower mosaic virus (CaMV) were tagged with β-glucuronidase (GUS) and green fluorescent protein (GFP) reporter genes to check the efficacy of the promoters. Histochemical staining of GUS in transformed tobacco (Nicotiana tabacum cv. Xanthi) leaves showed higher GUS expression driven by CLCuBuV Rep (complimentary sense) promoter as compared to conventional CaMV 35S promoter and CLCuBuV CP (virion sense) promoter, respectively. GUS activity in individual plant cells driven by CLCuBuV Rep, CLCuBuV CP, and CaMV 35S promoter were quantified through fluorometric GUS assay and reverse transcription quantitative real-time PCR (RT-qPCR). The expression level of GUS tagged with CLCuBuV Rep promoter in the transformed tobacco plants was obtained 2 to 4 fold higher than CaMV 35S promoter. When CLCuBuV CP promoter was used, lower expression level was monitored than that by CaMV 35S promoter. The expression of GFP-tagged with CLCuBuV promoters was also investigated through agroinfiltration. The CLCuBuV Rep promoters showed stronger consistent transient expression in the leaves of N. benthamiana, N. tabacum and Gossypium hirsutum plants when compared with CaMV 35S and CLCuBuV CP promoter.

Keywords: Begmovirus, bidirectional promoter, CaMV 35S promoter, GFP, GUS, qPCR

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Authors: Hamidrza Joodaki

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The most complex issue in urban land use planning is site selection that needs to assess the verity of elements and factors. Multi Criteria Decision Making (MCDM) methods are the best approach to deal with complex problems. In this paper, combination of the analytical hierarchy process (AHP) model and FUZZY logic was used as MCDM methods to select the best site for gas station in the 4th gas zone of Tehran. The first and the most important step in FUZZY-AHP model is selection of criteria and sub-criteria. Population, accessibility, proximity and natural disasters were considered as the main criteria in this study. After choosing the criteria, they were weighted based on AHP by EXPERT CHOICE software, and FUZZY logic was used to enhance accuracy and to approach the reality. After these steps, criteria layers were produced and weighted based on FUZZY-AHP model in GIS. Finally, through ARC GIS software, the layers were integrated and the 4th gas zone in TEHRAN was selected as the best site to locate gas station.

Keywords: multiple criteria decision making (MCDM), analytic hierarchy process (AHP), FUZZY logic, geographic information system (GIS)

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Authors: Fatima Chaudhary, Rehan Ul Haq

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Spatial and anthropogenic factors influencing nest-site selection in birds need to be identified for effective conservative practices. Environmental attributes such as food availability, predator density, previous reproductive success, etc., provide information regarding the site's quality. An artificial nest box experiment was carried out to evaluate the effect of various factors on nest-site selection, as it is hard to assess the natural cavities. The experiment was conducted whereby half of the boxes were filled with old nest material. Artificial nest boxes created with different materials and different sizes and colors were installed at different heights. A total of 14 out of 60 nest boxes were occupied and four of them faced predation. The birds explored a total of 32 out of 60 nests, whereas anthropogenic factors destroyed 25 out of 60 nests. Birds chose empty nest boxes at higher rates however, there was no obvious avoidance of sites having high ectoparasites load due to old nest material. It is also possible that the preference towards the artificial nest boxes may differ from year to year because of several climatic factors and the age of old nest material affecting the parasite's survival. These variables may fluctuate from one season to another. Considering these factors, nest-site selection experiments concerning the effectiveness of artificial nest boxes should be carried out over several successive seasons. This topic may stimulate further studies, which could lead to a fully understanding the birds' evolutionary ecology. Precise information on these factors influencing nest-site selection can be essential from an economic point of view as well.

Keywords: artificial nesting, nest box, old nest material, birds

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Authors: Ji-Young Choi, Jungjin Kim, Sang-Sun Yun, Sangmee Ahn Jo

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Intracellular adhesion molecule1 (ICAM1) is a mediator of inflammation and involved in adhesion and transmigration of leukocytes to endothelial cells, resulting in enhancement of brain inflammation. We hypothesized that increase of ICAM1 expression in endothelial cells is an early step in the pathogenesis of brain diseases such as Alzheimer’s disease. Here, we report that ICAM1 expression is regulated by pro-inflammatory cytokine TNFa in human microvascular endothelial cell (HBMVEC). TNFa significantly increased ICAM1 mRNA and protein levels at the concentrations showing no cell toxicity. This increase was also shown in micro vessels of mouse brain 24 hours after treatment with TNFa (8 mg/kg, i.v). We then investigated the epigenetic mechanism involved in the induction of ICAM1 expression. Chromatin immunoprecipitation assay revealed that TNFa reduced methylation of histone3K9 (H3K9-2me) and histone3K27 (H3K27-3me), well-known modification as gene suppression, with in the ICAM1 promoter region. However, acetylation of H3K9 and H3K14, well-known modification as gene activation, was not changed by TNFa. Treatment of BIX01294, a specific inhibitor of histone methyltransferase G9a responsible for H3K9-2me, dramatically increased in ICAM1 mRNA and protein levels and overexpression of G9a gene suppressed TNFa-induced ICAM1 expression. In contrast, GSK126, an inhibitor of histone methyltransferase EZH2 responsible for H3K27-3me and valproic acid, an inhibitor of histone deacetylase (HDAC) did not affect ICAM1 expression. These results suggested that histone3 methylation is involved in ICAM1 repression. Moreover, TNFa or BIX01294-induced ICAM induction resulted in both enhancements in adhesion and transmigration of leukocyte on endothelial cell. This study demonstrates that TNFa upregulates ICAM1 expression through H3K9-2me and H3K27-3me within the ICAM1 promoter region, in which G9a is likely to play a pivotal role in ICAM1 transcription. Our study provides a novel mechanism for ICAM1 transcription regulation in HBMVEC.

Keywords: ICAM1, TNFa, HBMVEC, H3K9-2me

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Authors: Jianli Dong, Fangling Xu, Gengming Huang

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Human endogenous retroviral elements (HERVs) comprise approximately 8% of the human genome. They are thought to be germline-integrated genetic remnants of retroviral infections. Although HERV sequences are highly defective, some, especially the K type (HERV-K), have been shown to be expressed and may have biological activities in the pathogenesis of cancer, chronic inflammation and autoimmune diseases. We found that HERV-K GAG and ENV proteins were strongly expressed in pleomorphic melanoma cells. We also detected a critical role of HERV-K ENV in mediating intercellular fusion and colony formation of melanoma cells. Interestingly, we found that levels of HERV-K GAG and ENV expression correlated with the activation of ERK and loss of p16INK4A in melanoma cells, and inhibition of MEK or CDK4, especially in combination, reduced HERV-K expression in melanoma cells. We also performed a reverse transcription-polymerase chain reaction (RT-PCR) assay using DNase I digestion to remove “contaminating” HERV-K genomic DNA and examined HERV-K RNA expression in plasma samples from HIV-1 infected individuals. We found a covariation between HERV-K RNA expression and CD4 cell counts in HIV-1 positive samples. Although a causal link between HERV-K activation and melanoma development, and between HERV-K activation, HIV-1 infection and CD4 cell count have yet to be determined, existing data support the further research efforts in HERV-K.

Keywords: CD4 cell, HERV-K, HIV-1, melanoma

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Authors: A. M. Naraghi, V. Gonzalez, M. O'Sullivan, C. G. Walker, M. Poshdar, F. Ying, M. Abdelmegid

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Discrete Event Simulation (DES) and Agent Based Simulation (ABS) are two simulation approaches that have been proposed to support decision-making in the construction industry. Despite the wide use of these simulation approaches in the construction field, their applications for production and material planning is still limited. This is largely due to the dynamic and complex nature of construction material supply chain systems. Moreover, managing the flow of construction material is not well integrated with site logistics in traditional construction planning methods. This paper presents a hybrid of DES and ABS to simulate on-site and off-site material supply processes. DES is applied to determine the best production scenarios with information of on-site production systems, while ABS is used to optimize the supply chain network. A case study of a construction piling project in New Zealand is presented illustrating the potential benefits of using the proposed hybrid simulation model in construction material flow planning. The hybrid model presented can be used to evaluate the impact of different decisions on construction supply chain management.

Keywords: construction supply-chain management, simulation modeling, decision-support tools, hybrid simulation

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Authors: V. Sulakatko, F. U. Vogdt, I. Lill

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Construction technology and on-site construction activities have a direct influence on the life cycle costs of energy efficiently renovated apartment buildings. The systematic inadequacies of the External Thermal Insulation Composite System (ETICS) which occur during the construction phase increase the risk for all stakeholders, reduce mechanical durability and increase the life cycle costs of the building. The economic effect of these shortcomings can be minimised if the risk of the most significant on-site activities is recognised. The objective of the presented ETICS economic assessment concept is to evaluate the economic influence of on-site shortcomings and reveal their significance to the foreseeable future repair costs. The model assembles repair techniques, discusses their direct cost calculation methods, argues over the proper usage of net present value over the life cycle of the building, and proposes a simulation tool to evaluate the risk of on-site activities. As the technique is dependent on the selected real interest rate, a sensitivity analysis is anticipated to determine the validity of the recommendations. After the verification of the model on the sample buildings by the industry, it is expected to increase economic rationality of resource allocation and reduce high-risk systematic shortcomings during the construction process of ETICS.

Keywords: activity-based cost estimating, cost estimation, ETICS, life cycle costing

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Authors: Ziyda Abunada

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In-situ remediation of contaminated land with deep mixing can deliver a multi-technique remedial strategy. A field trail includes permeable reactive barrier (PRB) took place at a severely contaminated site in Yorkshire to the north of the UK through the SMiRT (Soil Mix Remediation Technology) project in May 2011. SMiRT involved the execution of the largest research field trials in the UK to provide field validation. Innovative modified bentonite materials in combination with zeolite and organoclay were used to construct six different walls of a hexagonal PRB. Field monitoring, testing and site cores were collected from the PRB twice: once 2 months after the construction and again in March 2014 (almost 34 months later).This paper presents an overview of the results of the PRB materials’ relative performance with some initial 3-year time-related assessment. Results from the monitoring program and the site cores are presented. Some good correlations are seen together with some clear difference among the materials’ efficiency. These preliminary observations represent a potential for further investigations and highlighted the main lessons learned in a filed scale.

Keywords: in-situ remediation, groundwater, permeable reactive barrier, site cores

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Authors: Yousef S. Al-Othman

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The growth and expansion of the industrial facilities comes proportional to the market increasing demand of products and services. Furthermore, raw material producers such as oil companies usually undergo massive revamping projects to maintain a synchronized supply. These revamping projects are usually delivered through challenging construction projects held and associated with daily site risks related to the construction process. Henceforth, a case study related to these risks and corresponding on-spot corrective measurements has been made on a certain number of construction project contractors at Kuwait Oil Company (KOC) to derive the benefits and overall effectiveness of the on-spot corrective measurements during the construction phase of a project, and how would the same help in avoiding major incidents, ensuring a smooth, cost effective and on time delivery of the project. Findings of this case study shall have an added value to the overall risk management process by minimizing the daily site risks that may affect the project lead time, resulting in an undisturbed on-site construction process.

Keywords: oil and gas, risk management, construction projects, project lead time

Procedia PDF Downloads 107