Search results for: drug target
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 4539

Search results for: drug target

2949 Anti-Apoptotic Effect of Pueraria tuberosa in Rats with Streptozotocin Induced Diabetic Nephropathy

Authors: Rashmi Shukla, Yamini Bhusan Tripathi

Abstract:

Diabetic nephropathy (DN) is characterized as diabetic kidney disease which involves many pathways e.g. hyperactivated protein kinase c (PKC), polyol pathway, excess production of advanced glycation end product (AGEs) & free radical accumulation etc. All of them results to hypoxia followed by apoptosis of podocytes, glomerulosclerosis, extracellular matrix (ECM) accumulation and fibrosis resulting to irreversible changes in kidney. This is continuously rising worldwide and there are not enough specific drugs, to retard its progress. Due to increasing side effects of allopathic drugs, interest in herbal remedies is growing. Earlier, we have reported that PTY-2 (a phytomedicine, derived from Pueraria tuberosa Linn.) inhibits the accumulation of extracellular matrix (ECM) through activation of MMP-9. Present study exhibited the therapeutic potential of Pueraria tuberosa in the prevention of podocytes apoptosis and modulation of nephrin expression in streptozotocin (STZ) induced DN rats. DN rats were produced by maintaining persistent hyperglycemia for 8 weeks by intra-peritoneal injection of 55 mg/kg streptozotocin (STZ). These rats were randomly divided in 2 groups, i.e. DN control, and DN+ water extract of Pueraria tuberosa (PTW). One group of age-matched normal rats served as non-diabetic control (group-1), The STZ induced DN rats (group-2) and DN+PTW treated rats (group-3). The PTW was orally administered (0.3g/kg) daily to group-2 rats and drug vector (1 ml of 10% tween 20) in control rats. The treatments were continued for 20 days and blood and urine samples were collected. Rats were then sacrificed to investigate the expression Bcl2, Bax and nephroprotective protein i.e. nephrin in kidney glomerulus. The effect of PTW was evaluated, we have found that the PTW significantly(p < .001) reversed the raised serum urea, serum creatinine, urine protein and improved the creatinine clearance in STZ induce diabetic nephropathy in rats and also significantly(p < .001) prevented the rise in urine albumin excretion. The Western blot analysis of kidney tissue homogenate showed increased expression of Bcl2 in PTW treated rats. The RT-PCR showed the increased expression and accumulation of nephrin mRNA. The confocal photomicrographs also supported the reduction of Bax and a simultaneous increase in Bcl2 and nephrin in glomerular podocytes. Hence, our finding suggests that the nephroprotective role of PTW is mediated via restoration of nephrin thus prevents the podocytes apoptosis and ameliorates diabetic nephropathy. The clinical trial of PTW would prove to be a potential food supplement/ drug of alternative medicine for patients with diabetic nephropathy in early stage.

Keywords: Pueraria tuberosa, diabetic nephropathy, anti-apoptosis, nephrin

Procedia PDF Downloads 217
2948 L2 Strategies in the English Translation of Fengshen Yanyi

Authors: Yanbin Cai

Abstract:

L2 Translation, or translation out of one’s native language, is often adopted for Chinese classical literature. The purpose of this study is to investigate problems arisen in this process and the strategies different from translation by native speakers. Texts selected for this study is a Ming dynasty novel, Fengshen Yanyi, written by Xu Zhonglin and translated into English by Gu Zhizhong. Translated proper names and dialogues are analyzed, followed with a review on translator’s shifting focus on text selection. The result reveals not the problem of linguistic incompetence or cultural negligence, but translation strategies adopted for specific purposes and target readers.

Keywords: L2 translation, Chinese literature, literature translation, Fengshen Yanyi

Procedia PDF Downloads 465
2947 Verification of Dosimetric Commissioning Accuracy of Flattening Filter Free Intensity Modulated Radiation Therapy and Volumetric Modulated Therapy Delivery Using Task Group 119 Guidelines

Authors: Arunai Nambi Raj N., Kaviarasu Karunakaran, Krishnamurthy K.

Abstract:

The purpose of this study was to create American Association of Physicist in Medicine (AAPM) Task Group 119 (TG 119) benchmark plans for flattening filter free beam (FFF) deliveries of intensity modulated radiation therapy (IMRT) and volumetric arc therapy (VMAT) in the Eclipse treatment planning system. The planning data were compared with the flattening filter (FF) IMRT & VMAT plan data to verify the dosimetric commissioning accuracy of FFF deliveries. AAPM TG 119 proposed a set of test cases called multi-target, mock prostate, mock head and neck, and C-shape to ascertain the overall accuracy of IMRT planning, measurement, and analysis. We used these test cases to investigate the performance of the Eclipse Treatment planning system for the flattening filter free beam deliveries. For these test cases, we generated two sets of treatment plans, the first plan using 7–9 IMRT fields and a second plan utilizing two arc VMAT technique for both the beam deliveries (6 MV FF, 6MV FFF, 10 MV FF and 10 MV FFF). The planning objectives and dose were set as described in TG 119. The dose prescriptions for multi-target, mock prostate, mock head and neck, and C-shape were taken as 50, 75.6, 50 and 50 Gy, respectively. The point dose (mean dose to the contoured chamber volume) at the specified positions/locations was measured using compact (CC‑13) ion chamber. The composite planar dose and per-field gamma analysis were measured with IMatriXX Evaluation 2D array with OmniPro IMRT Software (version 1.7b). FFF beam deliveries of IMRT and VMAT plans were comparable to flattening filter beam deliveries. Our planning and quality assurance results matched with TG 119 data. AAPM TG 119 test cases are useful to generate FFF benchmark plans. From the obtained data in this study, we conclude that the commissioning of FFF IMRT and FFF VMAT delivery were found within the limits of TG-119 and the performance of the Eclipse treatment planning system for FFF plans were found satisfactorily.

Keywords: flattening filter free beams, intensity modulated radiation therapy, task group 119, volumetric modulated arc therapy

Procedia PDF Downloads 146
2946 Bacteriophage Is a Novel Solution of Therapy Against S. aureus Having Multiple Drug Resistance

Authors: Sanjay Shukla, A. Nayak, R. K. Sharma, A. P. Singh, S. P. Tiwari

Abstract:

Excessive use of antibiotics is a major problem in the treatment of wounds and other chronic infections, and antibiotic treatment is frequently non-curative, thus alternative treatment is necessary. Phage therapy is considered one of the most promising approaches to treat multi-drug resistant bacterial pathogens. Infections caused by Staphylococcus aureus are very efficiently controlled with phage cocktails, containing a different individual phages lysate infecting a majority of known pathogenic S. aureus strains. The aim of the present study was to evaluate the efficacy of a purified phage cocktail for prophylactic as well as therapeutic application in mouse model and in large animals with chronic septic infection of wounds. A total of 150 sewage samples were collected from various livestock farms. These samples were subjected for the isolation of bacteriophage by the double agar layer method. A total of 27 sewage samples showed plaque formation by producing lytic activity against S. aureus in the double agar overlay method out of 150 sewage samples. In TEM, recovered isolates of bacteriophages showed hexagonal structure with tail fiber. In the bacteriophage (ØVS) had an icosahedral symmetry with the head size 52.20 nm in diameter and long tail of 109 nm. Head and tail were held together by connector and can be classified as a member of the Myoviridae family under the order of Caudovirale. Recovered bacteriophage had shown the antibacterial activity against the S. aureus in vitro. Cocktail (ØVS1, ØVS5, ØVS9, and ØVS 27) of phage lysate were tested to know in vivo antibacterial activity as well as the safety profile. Result of mice experiment indicated that the bacteriophage lysate were very safe, did not show any appearance of abscess formation, which indicates its safety in living system. The mice were also prophylactically protected against S. aureus when administered with cocktail of bacteriophage lysate just before the administration of S. aureuswhich indicates that they are good prophylactic agent. The S. aureusinoculated mice were completely recovered by bacteriophage administration with 100% recovery, which was very good as compere to conventional therapy. In the present study, ten chronic cases of the wound were treated with phage lysate, and follow up of these cases was done regularly up to ten days (at 0, 5, and 10 d). The result indicated that the six cases out of ten showed complete recovery of wounds within 10 d. The efficacy of bacteriophage therapy was found to be 60% which was very good as compared to the conventional antibiotic therapy in chronic septic wounds infections. Thus, the application of lytic phage in single dose proved to be innovative and effective therapy for the treatment of septic chronic wounds.

Keywords: phage therapy, S aureus, antimicrobial resistance, lytic phage, and bacteriophage

Procedia PDF Downloads 117
2945 Feedback of Using Set-Up Candid Clips as New Media

Authors: Miss Suparada Prapawong

Abstract:

The objectives were to analyze the using of new media in the form of set up candid clip that affects the product and presenter, to study the effectiveness of using new media in the form of set up candid clip in order to increase the circulation and audience satisfaction and to use the earned information and knowledge to develop the communication for publicizing and advertising via new media. This research is qualitative research based on questionnaire and in-depth interview from experts. The findings showed the advantages and disadvantages of communication for publicizing and advertising via new media in the form of set up candid clip including with the specific target group for this kind of advertising. It will be useful for fields of publicizing and advertising in the new media forms at the present.

Keywords: candid clip, communication, new media, social network

Procedia PDF Downloads 308
2944 The Use of Corpora in Improving Modal Verb Treatment in English as Foreign Language Textbooks

Authors: Lexi Li, Vanessa H. K. Pang

Abstract:

This study aims to demonstrate how native and learner corpora can be used to enhance modal verb treatment in EFL textbooks in mainland China. It contributes to a corpus-informed and learner-centered design of grammar presentation in EFL textbooks that enhances the authenticity and appropriateness of textbook language for target learners. The linguistic focus is will, would, can, could, may, might, shall, should, must. The native corpus is the spoken component of BNC2014 (hereafter BNCS2014). The spoken part is chosen because pedagogical purpose of the textbooks is communication-oriented. Using the standard query option of CQPweb, 5% of each of the nine modals was sampled from BNCS2014. The learner corpus is the POS-tagged Ten-thousand English Compositions of Chinese Learners (TECCL). All the essays under the 'secondary school' section were selected. A series of five secondary coursebooks comprise the textbook corpus. All the data in both the learner and the textbook corpora are retrieved through the concordance functions of WordSmith Tools (version, 5.0). Data analysis was divided into two parts. The first part compared the patterns of modal verbs in the textbook corpus and BNC2014 with respect to distributional features, semantic functions, and co-occurring constructions to examine whether the textbooks reflect the authentic use of English. Secondly, the learner corpus was analyzed in terms of the use (distributional features, semantic functions, and co-occurring constructions) and the misuse (syntactic errors, e.g., she can sings*.) of the nine modal verbs to uncover potential difficulties that confront learners. The analysis of distribution indicates several discrepancies between the textbook corpus and BNCS2014. The first four most frequent modal verbs in BNCS2014 are can, would, will, could, while can, will, should, could are the top four in the textbooks. Most strikingly, there is an unusually high proportion of can (41.1%) in the textbooks. The results on different meanings shows that will, would and must are the most problematic. For example, for will, the textbooks contain 20% more occurrences of 'volition' and 20% less of 'prediction' than those in BNCS2014. Regarding co-occurring structures, the textbooks over-represented the structure 'modal +do' across the nine modal verbs. Another major finding is that the structure of 'modal +have done' that frequently co-occur with could, would, should, and must is underused in textbooks. Besides, these four modal verbs are the most difficult for learners, as the error analysis shows. This study demonstrates how the synergy of native and learner corpora can be harnessed to improve EFL textbook presentation of modal verbs in a way that textbooks can provide not only authentic language used in natural discourse but also appropriate design tailed for the needs of target learners.

Keywords: English as Foreign Language, EFL textbooks, learner corpus, modal verbs, native corpus

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2943 Genome Analyses of Pseudomonas Fluorescens b29b from Coastal Kerala

Authors: Wael Ali Mohammed Hadi

Abstract:

Pseudomonas fluorescens B29B, which has asparaginase enzymatic activity, was isolated from the surface coastal seawater of Trivandrum, India. We report the complete Pseudomonas fluorescens B29B genome sequenced, identified, and annotated from a marine source. We find the genome at most minuscule a 7,331,508 bp single circular chromosome with a GC content of 62.19% and 6883 protein-coding genes. Three hundred forty subsystems were identified, including two predicted asparaginases from the genome analysis of P. fluorescens B29B for further investigation. This genome data will help further industrial biotechnology applications of proteins in general and asparaginase as a target.

Keywords: pseudomonas, marine, asparaginases, Kerala, whole-genome

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2942 Translation as a Foreign Language Teaching Tool: Results of an Experiment with University Level Students in Spain

Authors: Nune Ayvazyan

Abstract:

Since the proclamation of monolingual foreign-language learning methods (the Berlitz Method in the early 20ᵗʰ century and the like), the dilemma has been to allow or not to allow learners’ mother tongue in the foreign-language learning process. The reason for not allowing learners’ mother tongue is reported to create a situation of immersion where students will only use the target language. It could be argued that this artificial monolingual situation is defective, mainly because there are very few real monolingual situations in the society. This is mainly due to the fact that societies are nowadays increasingly multilingual as plurilingual speakers are the norm rather than an exception. More recently, the use of learners’ mother tongue and translation has been put under the spotlight as valid foreign-language teaching tools. The logic dictates that if learners were permitted to use their mother tongue in the foreign-language learning process, that would not only be natural, but also would give them additional means of participation in class, which could eventually lead to learning. For example, when learners’ metalinguistic skills are poor in the target language, a question they might have could be asked in their mother tongue. Otherwise, that question might be left unasked. Attempts at empirically testing the role of translation as a didactic tool in foreign-language teaching are still very scant. In order to fill this void, this study looks into the interaction patterns between students in two kinds of English-learning classes: one with translation and the other in English only (immersion). The experiment was carried out with 61 students enrolled in a second-year university subject in English grammar in Spain. All the students underwent the two treatments, classes with translation and in English only, in order to see how they interacted under the different conditions. The analysis centered on four categories of interaction: teacher talk, teacher-initiated student interaction, student-initiated student-to-teacher interaction, and student-to-student interaction. Also, pre-experiment and post-experiment questionnaires and individual interviews gathered information about the students’ attitudes to translation. The findings show that translation elicited more student-initiated interaction than did the English-only classes, while the difference in teacher-initiated interactional turns was not statistically significant. Also, student-initiated participation was higher in comprehension-based activities (into L1) as opposed to production-based activities (into L2). As evidenced by the questionnaires, the students’ attitudes to translation were initially positive and mainly did not vary as a result of the experiment.

Keywords: foreign language, learning, mother tongue, translation

Procedia PDF Downloads 162
2941 Set Up Candid Clips Effectiveness

Authors: P. Suparada, D. Eakapotch

Abstract:

The objectives were to analyze the using of new media in the form of set up candid clip that affects the product and presenter, to study the effectiveness of using new media in the form of set up candid clip in order to increase the circulation and audience satisfaction and to use the earned information and knowledge to develop the communication for publicizing and advertising via new media. This research is qualitative research based on questionnaire and in-depth interview from experts. The findings showed the advantages and disadvantages of communication for publicizing and advertising via new media in the form of set up candid clip including with the specific target group for this kind of advertising. It will be useful for fields of publicizing and advertising in the new media forms at the present.

Keywords: candid clip, communication, new media, social network

Procedia PDF Downloads 246
2940 The Regulation of the Cancer Epigenetic Landscape Lies in the Realm of the Long Non-coding RNAs

Authors: Ricardo Alberto Chiong Zevallos, Eduardo Moraes Rego Reis

Abstract:

Pancreatic adenocarcinoma (PDAC) patients have a less than 10% 5-year survival rate. PDAC has no defined diagnostic and prognostic biomarkers. Gemcitabine is the first-line drug in PDAC and several other cancers. Long non-coding RNAs (lncRNAs) contribute to the tumorigenesis and are potential biomarkers for PDAC. Although lncRNAs aren’t translated into proteins, they have important functions. LncRNAs can decoy or recruit proteins from the epigenetic machinery, act as microRNA sponges, participate in protein translocation through different cellular compartments, and even promote chemoresistance. The chromatin remodeling enzyme EZH2 is a histone methyltransferase that catalyzes the methylation of histone 3 at lysine 27, silencing local expression. EZH2 is ambivalent, it can also activate gene expression independently of its histone methyltransferase activity. EZH2 is overexpressed in several cancers and interacts with lncRNAs, being recruited to a specific locus. EZH2 can be recruited to activate an oncogene or silence a tumor suppressor. The lncRNAs misregulation in cancer can result in the differential recruitment of EZH2 and in a distinct epigenetic landscape, promoting chemoresistance. The relevance of the EZH2-lncRNAs interaction to chemoresistant PDAC was assessed by Real Time quantitative PCR (RT-qPCR) and RNA Immunoprecipitation (RIP) experiments with naïve and gemcitabine-resistant PDAC cells. The expression of several lncRNAs and EZH2 gene targets was evaluated contrasting naïve and resistant cells. Selection of candidate genes was made by bioinformatic analysis and literature curation. Indeed, the resistant cell line showed higher expression of chemoresistant-associated lncRNAs and protein coding genes. RIP detected lncRNAs interacting with EZH2 with varying intensity levels in the cell lines. During RIP, the nuclear fraction of the cells was incubated with an antibody for EZH2 and with magnetic beads. The RNA precipitated with the beads-antibody-EZH2 complex was isolated and reverse transcribed. The presence of candidate lncRNAs was detected by RT-qPCR, and the enrichment was calculated relative to INPUT (total lysate control sample collected before RIP). The enrichment levels varied across the several lncRNAs and cell lines. The EZH2-lncRNA interaction might be responsible for the regulation of chemoresistance-associated genes in multiple cancers. The relevance of the lncRNA-EZH2 interaction to PDAC was assessed by siRNA knockdown of a lncRNA, followed by the analysis of the EZH2 target expression by RT-qPCR. The chromatin immunoprecipitation (ChIP) of EZH2 and H3K27me3 followed by RT-qPCR with primers for EZH2 targets also assess the specificity of the EZH2 recruitment by the lncRNA. This is the first report of the interaction of EZH2 and lncRNAs HOTTIP and PVT1 in chemoresistant PDAC. HOTTIP and PVT1 were described as promoting chemoresistance in several cancers, but the role of EZH2 is not clarified. For the first time, the lncRNA LINC01133 was detected in a chemoresistant cancer. The interaction of EZH2 with LINC02577, LINC00920, LINC00941, and LINC01559 have never been reported in any context. The novel lncRNAs-EZH2 interactions regulate chemoresistant-associated genes in PDAC and might be relevant to other cancers. Therapies targeting EZH2 alone weren’t successful, and a combinatorial approach also targeting the lncRNAs interacting with it might be key to overcome chemoresistance in several cancers.

Keywords: epigenetics, chemoresistance, long non-coding RNAs, pancreatic cancer, histone modification

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2939 Synthesis of Crosslinked Konjac Glucomannan and Kappa Carrageenan Film with Glutaraldehyde

Authors: Sperisa Distantina, Fadilah, Mujtahid Kaavessina

Abstract:

Crosslinked konjac glucomannan and kappa carrageenan film were prepared by chemical crosslinking using glutaraldehyde (GA) as the crosslinking agent. The effect crosslinking on the swelling degree was investigated. Konjac glucomanan and its mixture with kappa carragenan film was immersed in GA solution and then thermally cured. The obtained crosslinked film was washed and soaked in the ethanol to remove the unreacted GA. The obtained film was air dried at room temperature to a constant weight. The infrared spectra and the value of swelling degree of obtained crosslinked film showed that glucomannan and kappa carrageenan was able to be crosslinked using glutaraldehyde by film immersion and curing method without catalyst. The crosslinked films were found to be pH sensitive, indicating a potential to be used in drug delivery polymer system.

Keywords: crosslinking, glucomannan, carrageenan, swelling

Procedia PDF Downloads 279
2938 A Concept Study to Assist Non-Profit Organizations to Better Target Developing Countries

Authors: Malek Makki

Abstract:

The main purpose of this research study is to assist non-profit organizations (NPOs) to better segment a group of least developing countries and to optimally target the most needier areas, so that the provided aids make positive and lasting differences. We applied international marketing and strategy approaches to segment a sub-group of candidates among a group of 151 countries identified by the UN-G77 list, and furthermore, we point out the areas of priorities. We use reliable and well known criteria on the basis of economics, geography, demography and behavioral. These criteria can be objectively estimated and updated so that a follow-up can be performed to measure the outcomes of any program. We selected 12 socio-economic criteria that complement each other: GDP per capita, GDP growth, industry value added, export per capita, fragile state index, corruption perceived index, environment protection index, ease of doing business index, global competitiveness index, Internet use, public spending on education, and employment rate. A weight was attributed to each variable to highlight the relative importance of each criterion within the country. Care was taken to collect the most recent available data from trusted well-known international organizations (IMF, WB, WEF, and WTO). Construct of equivalence was carried out to compare the same variables across countries. The combination of all these weighted estimated criteria provides us with a global index that represents the level of development per country. An absolute index that combines wars and risks was introduced to exclude or include a country on the basis of conflicts and a collapsing state. The final step applied to the included countries consists of a benchmarking method to select the segment of countries and the percentile of each criterion. The results of this study allowed us to exclude 16 countries for risks and security. We also excluded four countries because they lack reliable and complete data. The other countries were classified per percentile thru their global index, and we identified the needier and the areas where aids are highly required to help any NPO to prioritize the area of implementation. This new concept is based on defined, actionable, accessible and accurate variables by which NPO can implement their program and it can be extended to profit companies to perform their corporate social responsibility acts.

Keywords: developing countries, international marketing, non-profit organization, segmentation

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2937 Menopause Hormone Therapy: An Insight into Knowledge and Attitudes of Obstetricians and Gynecologists in Singapore

Authors: Tan Hui Ying Renee, Stella Rizalina Sasha, Farah Safdar Husain

Abstract:

Introduction: Menopause Hormone Therapy (MHT) is an effective drug indicated for the treatment of menopausal symptoms and as replacement therapy in women who undergo premature menopause. In 2020, less than 8.8% of perimenopausal Singaporean women are on hormonal therapy, as compared to the Western population, where up to 50% may be on MHT. Factors associated with MHT utilization have been studied from patient characteristics, but the impact of locally prescribing physicians resulting in low MHT utilization has yet to be evaluated. The aim of the study is to determine the level of knowledge physicians in the Obstetrics and Gynaecology specialty have and their attitudes toward MHT. We believe that knowledge of MHT is lacking and that negative attitudes towards MHT may influence its use and undermine the benefits MHT may have for women. This paper is a part of a larger study on Singaporean physicians’ knowledge and attitudes towards MHT. Methods: This is a cross-sectional study intended to assess the knowledge and attitudes of physicians toward Menopausal Hormone Therapy. An anonymous questionnaire was disseminated via institutional internal circulations to optimize reach to physicians who may prescribe MHT, particularly in the fields of Gynaecology, Family Medicine and Endocrinology. Responses were completed voluntarily. Physicians had the option for each question to declare that they were ‘unsure’ or that the question was ‘beyond their expertise’. 21 knowledge questions tested factual recall on indications, contraindications, and risks of MHT. The remaining 6 questions were clinical scenarios crafted with the intention of testing specific principles related to the use of MHT. These questions received face validation from experts in the field. 198 responses were collected, 79 of which were from physicians in the Obstetrics and Gynaecology specialty. The data will be statistically analyzed to investigate areas that can be improved to increase the overall benefits of MHT for the Singaporean population. Results: Preliminary results show that the prevailing factors that limit Singaporean gynecologists and obstetricians from prescribing MHT are a lack of knowledge of MHT and a lack of confidence in prescribing MHT. Risks and indications of MHT were not well known by many physicians, with the majority of the questions having more than 25% incorrect and ‘unsure’ as their reply. The clinical scenario questions revealed significant shortcomings in knowledge on how to navigate real-life challenges in MHT use, with 2 of 6 questions with more than 50% incorrect or ‘beyond their expertise’ as their reply. The portion of the questionnaire that investigated the attitudes of physicians showed that though a large majority believed MHT to be an effective drug, only 40.5% were confident in prescribing it. Conclusion: Physicians in the Obstetrics and Gynaecology specialty lack knowledge and confidence in MHT. Therefore, it is imperative to formulate solutions on both the individual and institutional levels to fill these gaps and ensure that MHT is used appropriately and prescribed to the patients who need it.

Keywords: menopause, menopause hormone therapy, physician factors, obstetrics and gynecology, menopausal symptoms, Singapore

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2936 HIV-1 Nef Mediates Host Invasion by Differential Expression of Alpha-Enolase

Authors: Reshu Saxena, R. K. Tripathi

Abstract:

HIV-1 transmission and spread involves significant host-virus interaction. Potential targets for prevention of HIV-1 lies at the site of mucosal barriers. Thus a better understanding of how HIV-1 infects target cells at such sites and lead their invasion is required, with prime focus on the host determinants regulating HIV-1 spread. HIV-1 Nef is important for viral infectivity and pathogenicity. It promotes HIV-1 replication, facilitating immune evasion by interacting with various host factors and altering cellular pathways via multiple protein-protein interactions. In this study nef was sequenced from HIV-1 patients, and showed specific mutations revealing sequence variability in nef. To explore the difference in Nef functionality based on sequence variability we have studied the effects of HIV-1 Nef in human SupT1 T cell line and (THP-1) monocyte-macrophage cell lines through proteomics approach. 2D-Gel Electrophoresis in control and Nef-transfected SupT1 cells demonstrated several differentially expressed proteins with significant modulation of alpha-enolase. Through further studies, effects of Nef on alpha-enolase regulation were found to be cell lineage-specific, being stimulatory in macrophages/monocytes, inhibitory in T cells and without effect in HEK-293 cells. Cell migration and invasion studies were employed to determine biological function affected by Nef mediated regulation of alpha-enolase. Cell invasion was enhanced in THP-1 cells but was inhibited in SupT1 cells by wildtype nef. In addition, the modulation of enolase and cell invasion remained unaffected by a unique nef variant. These results indicated that regulation of alpha-enolase expression and invasive property of host cells by Nef is sequence specific, suggesting involvement of a particular motif of Nef. To precisely determine this site, we designed a heptapeptide including the suggested alpha-enolase regulating sequence of nef and a nef mutant with deletion of this site. Macrophages/monocytes being the major cells affected by HIV-1 at mucosal barriers, were particularly investigated by the nef mutant and peptide. Both the nef mutant and heptapeptide led to inhibition of enhanced enolase expression and increased invasiveness in THP-1 cells. Together, these findings suggest a possible mechanism of host invasion by HIV-1 through Nef mediated regulation of alpha-enolase and identifies a potential therapeutic target for HIV-1 entry at mucosal barriers.

Keywords: HIV-1 Nef, nef variants, host-virus interaction, tissue invasion

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2935 Gabriel Marcel and Friedrich Nietzsche: Existence and Death of God

Authors: Paolo Scolari

Abstract:

Nietzschean thought flows like a current throughout Marcel’s philosophy. Marcel is in constant dialogue with him. He wants to give homage to him, making him one of the most eminent representatives of existential thought. His enthusiasm is triggered by Nietzsche’s phrase: ‘God is dead,’ the fil rouge that ties all of the Nietzschean references scattered through marcelian texts. The death of God is the theme which emphasises both the greatness and simultaneously the tragedy of Nietzsche. Marcel wants to substitute the idea ‘God is dead’ with its original meaning: a tragic existential characteristic that imitators of Nietzsche seemed to have blurred. An interpretation that Marcel achieves aiming at double target. On the one hand he removes the heavy metaphysical suit from Nietzsche’s aphorisms on the death of God, that his interpreters have made them wear – Heidegger especially. On the other hand, he removes a stratus of trivialisation which takes the aphorisms out of context and transforms them into advertising slogans – here Sartre becomes the target. In the lecture: Nietzsche: l'homme devant la mort de dieu, Marcel hurls himself against the metaphysical Heidegger interpretation of the death of God. A hermeneutical proposal definitely original, but also a bit too abstract. An interpretation without bite, that does not grasp the tragic existential weight of the original Nietzschean idea. ‘We are probably on the wrong road,’ announces, ‘when at all costs, like Heidegger, we want to make a metaphysic out of Nietzsche.’ Marcel also criticizes Sartre. He lands in Geneva and reacts to the journalists, by saying: ‘Gentlemen, God is dead’. Marcel only needs this impromptu exclamation to understand how Sartre misinterprets the meaning of the death of God. Sartre mistakes and loses the existential sense of this idea in favour of the sensational and trivialisation of it. Marcel then wipes the slate clean from these two limited interpretations of the declaration of the death of God. This is much more than a metaphysical quarrel and not at all comparable to any advertising slogan. Behind the cry ‘God is dead’ there is the existence of an anguished man who experiences in his solitude the actual death of God. A man who has killed God with his own hands, haunted by the chill that from now on he will have to live in a completely different way. The death of God, however, is not the end. Marcel spots a new beginning at the point in which nihilism is overcome and the Übermensch is born. Dialoguing with Nietzsche he notices to being in the presence of a great spirit that has contributed to the renewal of a spiritual horizon. He descends to the most profound depths of his thought, aware that the way out is really far below, in the remotest areas of existence. The ambivalence of Nietzsche does not scare him. Rather such a thought, characterised by contradiction, will simultaneously be infinitely dangerous and infinitely healthy.

Keywords: Nietzsche's Death of God, Gabriel Marcel, Heidegger, Sartre

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2934 Redox-labeled Electrochemical Aptasensor Array for Single-cell Detection

Authors: Shuo Li, Yannick Coffinier, Chann Lagadec, Fabrizio Cleri, Katsuhiko Nishiguchi, Akira Fujiwara, Soo Hyeon Kim, Nicolas Clément

Abstract:

The need for single cell detection and analysis techniques has increased in the past decades because of the heterogeneity of individual living cells, which increases the complexity of the pathogenesis of malignant tumors. In the search for early cancer detection, high-precision medicine and therapy, the technologies most used today for sensitive detection of target analytes and monitoring the variation of these species are mainly including two types. One is based on the identification of molecular differences at the single-cell level, such as flow cytometry, fluorescence-activated cell sorting, next generation proteomics, lipidomic studies, another is based on capturing or detecting single tumor cells from fresh or fixed primary tumors and metastatic tissues, and rare circulating tumors cells (CTCs) from blood or bone marrow, for example, dielectrophoresis technique, microfluidic based microposts chip, electrochemical (EC) approach. Compared to other methods, EC sensors have the merits of easy operation, high sensitivity, and portability. However, despite various demonstrations of low limits of detection (LOD), including aptamer sensors, arrayed EC sensors for detecting single-cell have not been demonstrated. In this work, a new technique based on 20-nm-thick nanopillars array to support cells and keep them at ideal recognition distance for redox-labeled aptamers grafted on the surface. The key advantages of this technology are not only to suppress the false positive signal arising from the pressure exerted by all (including non-target) cells pushing on the aptamers by downward force but also to stabilize the aptamer at the ideal hairpin configuration thanks to a confinement effect. With the first implementation of this technique, a LOD of 13 cells (with5.4 μL of cell suspension) was estimated. In further, the nanosupported cell technology using redox-labeled aptasensors has been pushed forward and fully integrated into a single-cell electrochemical aptasensor array. To reach this goal, the LOD has been reduced by more than one order of magnitude by suppressing parasitic capacitive electrochemical signals by minimizing the sensor area and localizing the cells. Statistical analysis at the single-cell level is demonstrated for the recognition of cancer cells. The future of this technology is discussed, and the potential for scaling over millions of electrodes, thus pushing further integration at sub-cellular level, is highlighted. Despite several demonstrations of electrochemical devices with LOD of 1 cell/mL, the implementation of single-cell bioelectrochemical sensor arrays has remained elusive due to their challenging implementation at a large scale. Here, the introduced nanopillar array technology combined with redox-labeled aptamers targeting epithelial cell adhesion molecule (EpCAM) is perfectly suited for such implementation. Combining nanopillar arrays with microwells determined for single cell trapping directly on the sensor surface, single target cells are successfully detected and analyzed. This first implementation of a single-cell electrochemical aptasensor array based on Brownian-fluctuating redox species opens new opportunities for large-scale implementation and statistical analysis of early cancer diagnosis and cancer therapy in clinical settings.

Keywords: bioelectrochemistry, aptasensors, single-cell, nanopillars

Procedia PDF Downloads 117
2933 Influence of Heliotropium Undulatum on Hepatic Glutathione Conjugating Enzymes System in Acetylhydrazide-Rats

Authors: S. Ameddah, O. Deffa, H. Aissaoui, A. Menad, R. Mekkiou, F. Benayache, S. Benayache

Abstract:

Acetylhydrazide (ACHD) is a metabolite of the anti-tubercular drug isoniazid (INH) that has been implicated in liver damage. This study was designed to evaluate hapatoprotective of n-BuOH extract of Heliotrpium undulatum (HUBE) in ACHD hepatotoxicity in rats. Hepatic damage was induced by administration of ACHD (300 mg/Kg op). The protection was affected by the administration of HUBE (200 mg/Kg op) for 14 days before ACHD administration, caused a decrease in LPO levels and in the transaminase and ALP levels and restored the GSH and its related enzymes (GPx, GST, GR) (50-62 %). Simultaneous administration of HUBE afforded a partial protection in statue of hepatic GSH conjugating enzymes upon administration of ACHD.

Keywords: heliotrpium undulatum, acetylhydrazide, glutathione conjugating enzymes, oxydatif stress, heaptoprotectif effect

Procedia PDF Downloads 312
2932 Large-Scale Experimental and Numerical Studies on the Temperature Response of Main Cables and Suspenders in Bridge Fires

Authors: Shaokun Ge, Bart Merci, Fubao Zhou, Gao Liu, Ya Ni

Abstract:

This study investigates the thermal response of main cables and suspenders in suspension bridges subjected to vehicle fires, integrating large-scale gasoline pool fire experiments with numerical simulations. Focusing on a suspension bridge in China, the research examines the impact of wind speed, pool size, and lane position on flame dynamics and temperature distribution along the cables. The results indicate that higher wind speeds and larger pool sizes markedly increase the mass burning rate, causing flame deflection and non-uniform temperature distribution along the cables. Under a wind speed of 1.56 m/s, maximum temperatures reached approximately 960 ℃ near the base in emergency lane fires and 909 ℃ at 1.6 m height for slow lane fires, underscoring the heightened thermal risk from emergency lane fires. The study recommends a zoning strategy for cable fire protection, suggesting a 0-12.8 m protection zone with a target temperature of 1000 ℃ and a 12.8-20.8 m zone with a target temperature of 700 ℃, both with a 90-minute fire resistance. This approach, based on precise temperature distribution data from experimental and simulation results, provides a vital reference for the fire protection design of suspension bridge cables. Understanding cable temperature response during vehicle fires is crucial for developing fire protection systems, as it dictates necessary structural protection, fire resistance duration, and maximum temperatures for mitigation. Challenges of controlling environmental wind in large-scale fire tests are also addressed, along with a call for further research on fire behavior mechanisms and structural temperature response in cable-supported bridges under varying wind conditions. Conclusively, the proposed zoning strategy enhances the theoretical understanding of near-field temperature response in bridge fires, contributing significantly to the field by supporting the design of passive fire protection systems for bridge cables, safeguarding their integrity under extreme fire conditions.

Keywords: bridge fire, temperature response, large-scale experiment, numerical simulations, fire protection

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2931 Jet Impingement Heat Transfer on a Rib-Roughened Flat Plate

Authors: A. H. Alenezi

Abstract:

Cooling by impingement jet is known to have a significant high local and average heat transfer coefficient which make it widely used in industrial cooling systems. The heat transfer characteristics of an impinging jet on rib-roughened flat plate has been investigated numerically. This paper was set out to investigate the effect of rib height on the heat transfer rate. Since the flow needs to have enough spacing after passing the rib to allow reattachment especially for high Reynolds numbers, this study focuses on finding the optimum rib height which would be the best to maximize the heat transfer rate downstream the plate. This investigation employs a round nozzle with hydraulic diameter (Dh) of 13.5 mm, Jet-to-target distance of (H/D) of 4, rib location=1.5D and and finally jet angels of 45˚ and 90˚ under the influence of Re =10,000.

Keywords: jet impingement, CFD, turbulence model, heat transfer

Procedia PDF Downloads 351
2930 Low Density Lipoprotein: The Culprit in the Development of Obesity

Authors: Ojiegbe Ikenna Nathan

Abstract:

Obesity is a medical condition in which excess body fat has accumulated to the extent that it leads to reduced life expectancy and or increased health problems. Obesity as a worldwide problem is seen clustered in the families and it moves from generation to generation. It causes some disabilities, mortality and morbidity if left unattended to. The predisposing factors to obesity are either genetic or environment in origin. Nevertheless, the main predisposing factor to obesity is the excessive consumption of food rich in low-density lipoprotein (LDL) such as organ meats, saturated fats etc. This low-density lipoprotein causes an increase in adipose tissue and complicates to obesity. There are varieties of obesity which one needs to take appropriate measures to avoid; such as android, gynoid and morbid obesity. Nonetheless, studies have shown that there is hope for the obese individuals, despite the cause, type and degree of their obesity. This is through the use of the different available treatment measures which increase in physical activities, caloric restrictions, drug therapy and surgical intervention.

Keywords: low-density, lipoprotein, culprit, obesity

Procedia PDF Downloads 400
2929 Nanoparticles Using in Chiral Analysis with Different Methods of Separation

Authors: Bounoua Nadia, Rebizi Mohamed Nadjib

Abstract:

Chiral molecules in relation to particular biological roles are stereoselective. Enantiomers differ significantly in their biochemical responses in a biological environment. Despite the current advancement in drug discovery and pharmaceutical biotechnology, the chiral separation of some racemic mixtures continues to be one of the greatest challenges because the available techniques are too costly and time-consuming for the assessment of therapeutic drugs in the early stages of development worldwide. Various nanoparticles became one of the most investigated and explored nanotechnology-derived nanostructures, especially in chirality, where several studies are reported to improve the enantiomeric separation of different racemic mixtures. The production of surface-modified nanoparticles has contributed to these limitations in terms of sensitivity, accuracy, and enantioselectivity that can be optimized and therefore makes these surface-modified nanoparticles convenient for enantiomeric identification and separation.

Keywords: chirality, enantiomeric recognition, selectors, analysis, surface-modified nanoparticles

Procedia PDF Downloads 94
2928 In-Flight Radiometric Performances Analysis of an Airborne Optical Payload

Authors: Caixia Gao, Chuanrong Li, Lingli Tang, Lingling Ma, Yaokai Liu, Xinhong Wang, Yongsheng Zhou

Abstract:

Performances analysis of remote sensing sensor is required to pursue a range of scientific research and application objectives. Laboratory analysis of any remote sensing instrument is essential, but not sufficient to establish a valid inflight one. In this study, with the aid of the in situ measurements and corresponding image of three-gray scale permanent artificial target, the in-flight radiometric performances analyses (in-flight radiometric calibration, dynamic range and response linearity, signal-noise-ratio (SNR), radiometric resolution) of self-developed short-wave infrared (SWIR) camera are performed. To acquire the inflight calibration coefficients of the SWIR camera, the at-sensor radiances (Li) for the artificial targets are firstly simulated with in situ measurements (atmosphere parameter and spectral reflectance of the target) and viewing geometries using MODTRAN model. With these radiances and the corresponding digital numbers (DN) in the image, a straight line with a formulation of L = G × DN + B is fitted by a minimization regression method, and the fitted coefficients, G and B, are inflight calibration coefficients. And then the high point (LH) and the low point (LL) of dynamic range can be described as LH= (G × DNH + B) and LL= B, respectively, where DNH is equal to 2n − 1 (n is the quantization number of the payload). Meanwhile, the sensor’s response linearity (δ) is described as the correlation coefficient of the regressed line. The results show that the calibration coefficients (G and B) are 0.0083 W·sr−1m−2µm−1 and −3.5 W·sr−1m−2µm−1; the low point of dynamic range is −3.5 W·sr−1m−2µm−1 and the high point is 30.5 W·sr−1m−2µm−1; the response linearity is approximately 99%. Furthermore, a SNR normalization method is used to assess the sensor’s SNR, and the normalized SNR is about 59.6 when the mean value of radiance is equal to 11.0 W·sr−1m−2µm−1; subsequently, the radiometric resolution is calculated about 0.1845 W•sr-1m-2μm-1. Moreover, in order to validate the result, a comparison of the measured radiance with a radiative-transfer-code-predicted over four portable artificial targets with reflectance of 20%, 30%, 40%, 50% respectively, is performed. It is noted that relative error for the calibration is within 6.6%.

Keywords: calibration and validation site, SWIR camera, in-flight radiometric calibration, dynamic range, response linearity

Procedia PDF Downloads 270
2927 Actualizing Millennium Development Goals through a Refocused Basic Mathematics Curriculum

Authors: Ali Yaro Kankia

Abstract:

Millennium Development Goals are eight goals set by the 189 United Nations member States with 2015 as its target year of achievement. Since its signing in September 2000, individual nations have been finding ways and means of actualizing them. This paper consider how a refocused basic Mathematics curriculum could serve as an appropriate tool in achieving these goals. This was done by considering the theme in the following sub-headings. Basic Mathematics curriculum before now, basic Mathematics curriculum and the millennium development Goals and challenges of a refocused basic Mathematics curriculum for the MDGs. The appropriate conclusion was reached.

Keywords: actualizing, curriculum, MDGs, refocused

Procedia PDF Downloads 389
2926 Guidance and Control of a Torpedo Autonomous Underwater Vehicle

Authors: Soheil Arash Moghadam, Abdol R. Kashani Nia, Ali Akrami Zade

Abstract:

Considering numerous applications of Autonomous Underwater Vehicles in various industries, there has been plenty of researches and studies on the motion control of such vehicles. One of the useful aspects for studying is the guidance of these vehicles. In this paper, while presenting motion equations with six degrees of freedom for Autonomous Underwater Vehicles, Proportional Navigation Guidance Law and the first order sliding mode control for TAIPAN AUV was used to address its guidance for the purpose of collision with a moving target.

Keywords: Autonomous Underwater Vehicle (AUV), degree of freedom (DOF), hydrodynamic, line of sight(LOS), proportional navigation guidance(PNG), sliding mode control(SMC)

Procedia PDF Downloads 468
2925 KPI and Tool for the Evaluation of Competency in Warehouse Management for Furniture Business

Authors: Kritchakhris Na-Wattanaprasert

Abstract:

The objective of this research is to design and develop a prototype of a key performance indicator system this is suitable for warehouse management in a case study and use requirement. In this study, we design a prototype of key performance indicator system (KPI) for warehouse case study of furniture business by methodology in step of identify scope of the research and study related papers, gather necessary data and users requirement, develop key performance indicator base on balance scorecard, design pro and database for key performance indicator, coding the program and set relationship of database and finally testing and debugging each module. This study use Balance Scorecard (BSC) for selecting and grouping key performance indicator. The system developed by using Microsoft SQL Server 2010 is used to create the system database. In regard to visual-programming language, Microsoft Visual C# 2010 is chosen as the graphic user interface development tool. This system consists of six main menus: menu login, menu main data, menu financial perspective, menu customer perspective, menu internal, and menu learning and growth perspective. Each menu consists of key performance indicator form. Each form contains a data import section, a data input section, a data searches – edit section, and a report section. The system generates outputs in 5 main reports, the KPI detail reports, KPI summary report, KPI graph report, benchmarking summary report and benchmarking graph report. The user will select the condition of the report and period time. As the system has been developed and tested, discovers that it is one of the ways to judging the extent to warehouse objectives had been achieved. Moreover, it encourages the warehouse functional proceed with more efficiency. In order to be useful propose for other industries, can adjust this system appropriately. To increase the usefulness of the key performance indicator system, the recommendations for further development are as follows: -The warehouse should review the target value and set the better suitable target periodically under the situation fluctuated in the future. -The warehouse should review the key performance indicators and set the better suitable key performance indicators periodically under the situation fluctuated in the future for increasing competitiveness and take advantage of new opportunities.

Keywords: key performance indicator, warehouse management, warehouse operation, logistics management

Procedia PDF Downloads 431
2924 High-Performance Liquid Chromatographic Method with Diode Array Detection (HPLC-DAD) Analysis of Naproxen and Omeprazole Active Isomers

Authors: Marwa Ragab, Eman El-Kimary

Abstract:

Chiral separation and analysis of omeprazole and naproxen enantiomers in tablets were achieved using high-performance liquid chromatographic method with diode array detection (HPLC-DAD). Kromasil Cellucoat chiral column was used as a stationary phase for separation and the eluting solvent consisted of hexane, isopropanol and trifluoroacetic acid in a ratio of: 90, 9.9 and 0.1, respectively. The chromatographic system was suitable for the enantiomeric separation and analysis of active isomers of the drugs. Resolution values of 2.17 and 3.84 were obtained after optimization of the chromatographic conditions for omeprazole and naproxen isomers, respectively. The determination of S-isomers of each drug in their dosage form was fully validated.

Keywords: chiral analysis, esomeprazole, S-Naproxen, HPLC-DAD

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2923 Response Surface Methodology for Optimum Hardness of TiN on Steel Substrate

Authors: R. Joseph Raviselvan, K. Ramanathan, P. Perumal, M. R. Thansekhar

Abstract:

Hard coatings are widely used in cutting and forming tool industries. Titanium Nitride (TiN) possesses good hardness, strength and corrosion resistant. The coating properties are influenced by many process parameters. The coatings were deposited on steel substrate by changing the process parameters such as substrate temperature, nitrogen flow rate and target power in a D.C planer magnetron sputtering. The structure of coatings were analysed using XRD. The hardness of coatings was found using Micro hardness tester. From the experimental data, a regression model was developed and the optimum response was determined using Response Surface Methodology (RSM).

Keywords: hardness, RSM, sputtering, TiN XRD

Procedia PDF Downloads 321
2922 Targeted Nano Anti-Cancer Drugs for Curing Cancers

Authors: Imran Ali

Abstract:

General chemotherapy for cancer treatment has many side and toxic effects. A new approach of targeting nano anti-cancer drug is under development stage and only few drugs are available in the market today. The unique features of these drugs are targeted action on cancer cells only without any side effect. Sometimes, these are called magic drugs. The important molecules used for nano anti-cancer drugs are cisplatin, carboplatin, bleomycin, 5-fluorouracil, doxorubicin, dactinomycin, 6-mercaptopurine, paclitaxel, topotecan, vinblastin and etoposide etc. The most commonly used materials for preparing nano particles carriers are dendrimers, polymeric, liposomal, micelles inorganic, organic etc. The proposed lecture will comprise the-of-art of nano drugs in cancer chemo-therapy including preparation, types of drugs, mechanism, future perspectives etc.

Keywords: cancer, nano-anti-cancer drugs, chemo-therapy, mechanism of action, future perspectives

Procedia PDF Downloads 448
2921 The Effect of Some Macrofungi Extracts on Cytoplasmic Membrane of Multidrug Resistant Bacteria by Flow Cytometry

Authors: Yener Tekeli, Hayri Baba

Abstract:

The natural active compounds found in medicinal plants are belong to various chemical structures including polyphenolic compounds, flavonoids, essential oils, and vitamins and some of these compounds have anticancer, antioxidant, and antimicrobial activity. However, these compounds have been little known about mechanisms to confer antibacterial drug resistance. In this study; some macrofungi extracts (Pholiota lucifera, Gnaoderma applanatum and Pleurotus ostreatus) were investigated for their abilities to enhance bacterial permeability by flow cytometry. This experiments exhibited enhancement of these extracts to disrupt the cytoplasmic membrane of living bacterial (Listeria innocua and Escherichia coli) cells. These experiments were designed to detect uptake of PI&SYT by enhancing with a ranged concentration of herb extracts.

Keywords: antimicrobial activity, flow cytometry, macrofungi, multidrug resistant

Procedia PDF Downloads 445
2920 Review on PETG Material Parts Made Using Fused Deposition Modeling

Authors: Dhval Chauhan, Mahesh Chudasama

Abstract:

This study has been undertaken to give a review of Polyethylene Terephthalate Glycol (PETG) material used in Fused Deposition Modelling (FDM). This paper offers a review of the existing literature on polyethylene terephthalate glycol (PETG) material, the objective of the paper is to providing guidance on different process parameters that can be used to improve the strength of the part by performing various testing like tensile, compressive, flexural, etc. This work is target to find new paths that can be used for further development of the use of fiber reinforcement in PETG material.

Keywords: PETG, FDM, tensile strength, flexural strength, fiber reinforcement

Procedia PDF Downloads 192