Search results for: genetic profiles
Commenced in January 2007
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Edition: International
Paper Count: 2620

Search results for: genetic profiles

400 Unequal Contributions of Parental Isolates in Somatic Recombination of the Stripe Rust Fungus

Authors: Xianming Chen, Yu Lei, Meinan Wang

Abstract:

The dikaryotic basidiomycete fungus, Puccinia striiformis, causes stripe rust, one of the most important diseases of wheat and barley worldwide. The pathogen is largely reproduced asexually, and asexual recombination has been hypothesized to be one of the mechanisms for the pathogen variations. To test the hypothesis and understand the genetic process of asexual recombination, somatic recombinant isolates were obtained under controlled conditions by inoculating susceptible host plants with a mixture of equal quantity of urediniospores of isolates with different virulence patterns and selecting through a series of inoculation on host plants with different genes for resistance to one of the parental isolates. The potential recombinant isolates were phenotypically characterized by virulence testing on the set of 18 wheat lines used to differentiate races of the wheat stripe rust pathogen, P. striiformis f. sp. tritici (Pst), for the combinations of Pst isolates; or on both sets of the wheat differentials and 12 barley differentials for identifying races of the barley stripe rust pathogen, P. striiformis f. sp. hordei (Psh) for combinations of a Pst isolate and a Psh isolate. The progeny and parental isolates were also genotypically characterized with 51 simple sequence repeat and 90 single-nucleotide polymorphism markers. From nine combinations of parental isolates, 68 potential recombinant isolates were obtained, of which 33 (48.5%) had similar virulence patterns to one of the parental isolates, and 35 (51.5%) had virulence patterns distinct from either of the parental isolates. Of the 35 isolates of distinct virulence patterns, 11 were identified as races that had been previously detected from natural collections and 24 were identified as new races. The molecular marker data confirmed 66 of the 68 isolates as recombinants. The percentages of parental marker alleles ranged from 0.9% to 98.9% and were significantly different from equal proportions in the recombinant isolates. Except for a couple of combinations, the greater or less contribution was not specific to any particular parental isolates as the same parental isolates contributed more to some of the progeny isolates but less to the other progeny isolates in the same combination. The unequal contributions by parental isolates appear to be a general role in somatic recombination for the stripe rust fungus, which may be used to distinguish asexual recombination from sexual recombination in studying the evolutionary mechanisms of the highly variable fungal pathogen.

Keywords: molecular markers, Puccinia striiformis, somatic recombination, stripe rust

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399 Management Practices and Economic Performance of Smallholder Dairy Cattle Farms in Southern Vietnam

Authors: Ngoc-Hieu Vu

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Although dairy production in Vietnam is a relatively new agricultural activity, milk production increased remarkably in recent years. Smallholders are still the main drivers for this development, especially in the southern part of the country. However, information on the farming practices is very limited. Therefore, this study aimed to characterize husbandry practices, educational experiences, decision-making practices, constraints, income and expenses of smallholder dairy farms in Southern Vietnam. A total of 200 farms, located in the regions Ho Chi Minh (HCM, N=80 farms), Lam Dong (N=40 farms), Binh Duong (N=40 farms) and Long An (N=40 farms) were included. Between October 2013 and December 2014 farmers were interviewed twice. On average, farms owned 3.200m2, 2.000m2, and 193m2 of pasture, cropping and housing area, respectively. The number of total, milking and dry cows, heifers, and calves were 20.4, 11.6, 4.7, 3.3, and 2.9 head. The number of lactating dairy cows was higher (p<0.001) in HCM (15.5) and Lam Dong (14.7) than in Binh Duong (6.7) and Long An (10.7). Animals were mainly crossbred Holstein-Friesian (HF) cows with at least 75% HF origin (84%), whereas a higher (P<0.001) percentage of purebred HF was found in HCM and Lam Dong and crossbreds in Binh Duong and Long An. Animals were mainly raised in tie-stalls (94%) and machine-milked (80%). Farmers used their own replacement animals (76%), and both genetic and phenotypic information (67%) for selecting sires. Farmers were predominantly educated at primary school level (53%). Major constraints for dairy farming were the lack of capital (43%), diseases (17%), marketing (22%), lack of knowledge (8%) and feed (7%). Monthly profit per lactating cow was superior in Lam Dong (2,817 thousand VND) and HCM (2,798 thousand VND) compared to other regions in Long An (2,597 thousand VND), and Binh Duong (1,775 thousand VND). Regional differences may be mainly attributed to environmental factors, urbanization, and particularly governmental support and the availability of extension and financial institutions. Results from this study provide important information on farming practices of smallholders in Southern Vietnam that are useful in determining regions that need to be addressed by authorities in order to improve dairy production.

Keywords: dairy farms, milk yield, Southern Vietnam, socio-economics

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398 MicroRNA-1246 Expression Associated with Resistance to Oncogenic BRAF Inhibitors in Mutant BRAF Melanoma Cells

Authors: Jae-Hyeon Kim, Michael Lee

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Intrinsic and acquired resistance limits the therapeutic benefits of oncogenic BRAF inhibitors in melanoma. MicroRNAs (miRNA) regulate the expression of target mRNAs by repressing their translation. Thus, we investigated miRNA expression patterns in melanoma cell lines to identify candidate biomarkers for acquired resistance to BRAF inhibitor. Here, we used Affymetrix miRNA V3.0 microarray profiling platform to compare miRNA expression levels in three cell lines containing BRAF inhibitor-sensitive A375P BRAF V600E cells, their BRAF inhibitor-resistant counterparts (A375P/Mdr), and SK-MEL-2 BRAF-WT cells with intrinsic resistance to BRAF inhibitor. The miRNAs with at least a two-fold change in expression between BRAF inhibitor-sensitive and –resistant cell lines, were identified as differentially expressed. Averaged intensity measurements identified 138 and 217 miRNAs that were differentially expressed by 2 fold or more between: 1) A375P and A375P/Mdr; 2) A375P and SK-MEL-2, respectively. The hierarchical clustering revealed differences in miRNA expression profiles between BRAF inhibitor-sensitive and –resistant cell lines for miRNAs involved in intrinsic and acquired resistance to BRAF inhibitor. In particular, 43 miRNAs were identified whose expression was consistently altered in two BRAF inhibitor-resistant cell lines, regardless of intrinsic and acquired resistance. Twenty five miRNAs were consistently upregulated and 18 downregulated more than 2-fold. Although some discrepancies were detected when miRNA microarray data were compared with qPCR-measured expression levels, qRT-PCR for five miRNAs (miR-3617, miR-92a1, miR-1246, miR-1936-3p, and miR-17-3p) results showed excellent agreement with microarray experiments. To further investigate cellular functions of miRNAs, we examined effects on cell proliferation. Synthetic oligonucleotide miRNA mimics were transfected into three cell lines, and proliferation was quantified using a colorimetric assay. Of the 5 miRNAs tested, only miR-1246 altered cell proliferation of A375P/Mdr cells. The transfection of miR-1246 mimic strongly conferred PLX-4720 resistance to A375P/Mdr cells, implying that miR-1246 upregulation confers acquired resistance to BRAF inhibition. We also found that PLX-4720 caused much greater G2/M arrest in A375P/Mdr cells transfected with miR-1246mimic than that seen in scrambled RNA-transfected cells. Additionally, miR-1246 mimic partially caused a resistance to autophagy induction by PLX-4720. These results indicate that autophagy does play an essential death-promoting role inPLX-4720-induced cell death. Taken together, these results suggest that miRNA expression profiling in melanoma cells can provide valuable information for a network of BRAF inhibitor resistance-associated miRNAs.

Keywords: microRNA, BRAF inhibitor, drug resistance, autophagy

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397 Enhancement of Mass Transport and Separations of Species in a Electroosmotic Flow by Distinct Oscillatory Signals

Authors: Carlos Teodoro, Oscar Bautista

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In this work, we analyze theoretically the mass transport in a time-periodic electroosmotic flow through a parallel flat plate microchannel under different periodic functions of the applied external electric field. The microchannel connects two reservoirs having different constant concentrations of an electro-neutral solute, and the zeta potential of the microchannel walls are assumed to be uniform. The governing equations that allow determining the mass transport in the microchannel are given by the Poisson-Boltzmann equation, the modified Navier-Stokes equations, where the Debye-Hückel approximation is considered (the zeta potential is less than 25 mV), and the species conservation. These equations are nondimensionalized and four dimensionless parameters appear which control the mass transport phenomenon. In this sense, these parameters are an angular Reynolds, the Schmidt and the Péclet numbers, and an electrokinetic parameter representing the ratio of the half-height of the microchannel to the Debye length. To solve the mathematical model, first, the electric potential is determined from the Poisson-Boltzmann equation, which allows determining the electric force for various periodic functions of the external electric field expressed as Fourier series. In particular, three different excitation wave forms of the external electric field are assumed, a) sawteeth, b) step, and c) a periodic irregular functions. The periodic electric forces are substituted in the modified Navier-Stokes equations, and the hydrodynamic field is derived for each case of the electric force. From the obtained velocity fields, the species conservation equation is solved and the concentration fields are found. Numerical calculations were done by considering several binary systems where two dilute species are transported in the presence of a carrier. It is observed that there are different angular frequencies of the imposed external electric signal where the total mass transport of each species is the same, independently of the molecular diffusion coefficient. These frequencies are called crossover frequencies and are obtained graphically at the intersection when the total mass transport is plotted against the imposed frequency. The crossover frequencies are different depending on the Schmidt number, the electrokinetic parameter, the angular Reynolds number, and on the type of signal of the external electric field. It is demonstrated that the mass transport through the microchannel is strongly dependent on the modulation frequency of the applied particular alternating electric field. Possible extensions of the analysis to more complicated pulsation profiles are also outlined.

Keywords: electroosmotic flow, mass transport, oscillatory flow, species separation

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396 Literature Review of Rare Synchronous Tumours

Authors: Diwei Lin, Amanda Tan, Rajinder Singh-Rai

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We present the first reported case of a concomitant Leydig cell tumor (LCT) and paratesticular leiomyoma in an adult male with a known history of bilateral cryptorchidism. An 80-year-old male presented with a 2-month history of a left testicular lump associated with mild discomfort and a gradual increase in size on a background of bilateral cryptorchidism requiring multiple orchidopexy procedures as a child. Ultrasound confirmed a lesion suspicious for malignancy and he proceeded to a left radical orchidectomy. Histopathological assessment of the left testis revealed a concomitant testicular LCT with malignant features and paratesticular leiomyoma. Leydig cell tumors (LCTs) are the most common pure testicular sex cord-stromal tumors, accounting for up to 3% of all testicular tumors. They can occur at almost any age, but are noted to have a bi-modal distribution, with a peak incidence at 6 to 10 and at 20 to 50 years of age. LCT’s are often hormonally active and can lead to feminizing or virilizing syndromes. LCT’s are usually regarded as benign but can rarely exhibit malignant traits. Paratesticular tumours are uncommon and their reported prevalence varies between 3% and 16%. They occur in a complex anatomical area which includes the contents of the spermatic cord, testicular tunics, epididymis and vestigial remnants. Up to 90% of paratesticular tumours are believed to originate from the spermatic cord, though it is often difficult to definitively ascertain the exact site of origin. Although any type of soft-tissue neoplasm can be found in the paratesticular region, the most common benign tumors reported are lipomas of the spermatic cord, adenomatoid tumours of the epididymis and leiomyomas of the testis. Genetic studies have identified potential mutations that could potentially cause LCTs, but there are no known associations between concomitant LCTs and paratesticular tumors. The presence of cryptorchidism in adults with both LCTs and paratesticular neoplasms individually has been previously reported and it appears intuitive that cryptorchidism is likely to be associated with the concomitant presentation in this case report. This report represents the first documented case in the literature of a unilateral concomitant LCT and paratesticular leiomyoma on a background of bilateral cryptorchidism.

Keywords: testicular cancer, leydig cell tumour, leiomyoma, paratesticular neoplasms

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395 Affects Associations Analysis in Emergency Situations

Authors: Joanna Grzybowska, Magdalena Igras, Mariusz Ziółko

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Association rule learning is an approach for discovering interesting relationships in large databases. The analysis of relations, invisible at first glance, is a source of new knowledge which can be subsequently used for prediction. We used this data mining technique (which is an automatic and objective method) to learn about interesting affects associations in a corpus of emergency phone calls. We also made an attempt to match revealed rules with their possible situational context. The corpus was collected and subjectively annotated by two researchers. Each of 3306 recordings contains information on emotion: (1) type (sadness, weariness, anxiety, surprise, stress, anger, frustration, calm, relief, compassion, contentment, amusement, joy) (2) valence (negative, neutral, or positive) (3) intensity (low, typical, alternating, high). Also, additional information, that is a clue to speaker’s emotional state, was annotated: speech rate (slow, normal, fast), characteristic vocabulary (filled pauses, repeated words) and conversation style (normal, chaotic). Exponentially many rules can be extracted from a set of items (an item is a previously annotated single information). To generate the rules in the form of an implication X → Y (where X and Y are frequent k-itemsets) the Apriori algorithm was used - it avoids performing needless computations. Then, two basic measures (Support and Confidence) and several additional symmetric and asymmetric objective measures (e.g. Laplace, Conviction, Interest Factor, Cosine, correlation coefficient) were calculated for each rule. Each applied interestingness measure revealed different rules - we selected some top rules for each measure. Owing to the specificity of the corpus (emergency situations), most of the strong rules contain only negative emotions. There are though strong rules including neutral or even positive emotions. Three examples of the strongest rules are: {sadness} → {anxiety}; {sadness, weariness, stress, frustration} → {anger}; {compassion} → {sadness}. Association rule learning revealed the strongest configurations of affects (as well as configurations of affects with affect-related information) in our emergency phone calls corpus. The acquired knowledge can be used for prediction to fulfill the emotional profile of a new caller. Furthermore, a rule-related possible context analysis may be a clue to the situation a caller is in.

Keywords: data mining, emergency phone calls, emotional profiles, rules

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394 Cosmic Radiation Hazards and Protective Strategies in Space Exploration

Authors: Mehrnaz Mostafavi, Alireza Azani, Mahtab Shabani, Fatemeh Ghafari

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While filled with promise and wonder, space exploration also presents significant challenges, one of the foremost being the threat of cosmic radiation to astronaut health. Recent advancements in assessing these risks and developing protective strategies have shed new light on this issue. Cosmic radiation encompasses a variety of high-energy particles originating from sources like solar particle events, galactic cosmic rays, and cosmic rays from beyond the solar system. These particles, composed of protons, electrons, and heavy ions, pose a substantial threat to human health in space due to the lack of Earth's protective atmosphere and magnetic field. Researchers have made significant progress in assessing the risks associated with cosmic radiation exposure. By employing advanced dosimetry techniques and conducting biological studies, they have gained insights into how cosmic radiation affects astronauts' health, including increasing the risk of cancer and radiation sickness. This research has led to personalized risk assessment methods tailored to individual astronaut profiles. Distinctive protection strategies have been proposed to combat the dangers of cosmic radiation. These include developing spacecraft shielding materials and designs to enhance radiation protection. Additionally, researchers are exploring pharmacological interventions such as radioprotective drugs and antioxidant therapies to mitigate the biological effects of radiation exposure and preserve astronaut well-being. The findings from recent research have significant implications for the future of space exploration. By advancing our understanding of cosmic radiation risks and developing effective protection strategies, we pave the way for safer and more sustainable human missions beyond Earth's orbit. This is especially crucial for long-duration missions to destinations like Mars, where astronauts will face prolonged exposure to cosmic radiation. In conclusion, recent research has marked a milestone in addressing the challenges posed by cosmic radiation in space exploration. By delving into the complexities of cosmic radiation exposure and developing innovative protection strategies, scientists are ensuring the health and resilience of astronauts as they venture into the vast expanse of the cosmos. Continued research and collaboration in this area are essential for overcoming the cosmic radiation challenge and enabling humanity to embark on new frontiers of exploration and discovery in space.

Keywords: Space exploration, cosmic radiation, astronaut health, risk assessment, protective strategies

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393 Reducing Pressure Drop in Microscale Channel Using Constructal Theory

Authors: K. X. Cheng, A. L. Goh, K. T. Ooi

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The effectiveness of microchannels in enhancing heat transfer has been demonstrated in the semiconductor industry. In order to tap the microscale heat transfer effects into macro geometries, overcoming the cost and technological constraints, microscale passages were created in macro geometries machined using conventional fabrication methods. A cylindrical insert was placed within a pipe, and geometrical profiles were created on the outer surface of the insert to enhance heat transfer under steady-state single-phase liquid flow conditions. However, while heat transfer coefficient values of above 10 kW/m2·K were achieved, the heat transfer enhancement was accompanied by undesirable pressure drop increment. Therefore, this study aims to address the high pressure drop issue using Constructal theory, a universal design law for both animate and inanimate systems. Two designs based on Constructal theory were developed to study the effectiveness of Constructal features in reducing the pressure drop increment as compared to parallel channels, which are commonly found in microchannel fabrication. The hydrodynamic and heat transfer performance for the Tree insert and Constructal fin (Cfin) insert were studied using experimental methods, and the underlying mechanisms were substantiated by numerical results. In technical terms, the objective is to achieve at least comparable increment in both heat transfer coefficient and pressure drop, if not higher increment in the former parameter. Results show that the Tree insert improved the heat transfer performance by more than 16 percent at low flow rates, as compared to the Tree-parallel insert. However, the heat transfer enhancement reduced to less than 5 percent at high Reynolds numbers. On the other hand, the pressure drop increment stayed almost constant at 20 percent. This suggests that the Tree insert has better heat transfer performance in the low Reynolds number region. More importantly, the Cfin insert displayed improved heat transfer performance along with favourable hydrodynamic performance, as compared to Cfinparallel insert, at all flow rates in this study. At 2 L/min, the enhancement of heat transfer was more than 30 percent, with 20 percent pressure drop increment, as compared to Cfin-parallel insert. Furthermore, comparable increment in both heat transfer coefficient and pressure drop was observed at 8 L/min. In other words, the Cfin insert successfully achieved the objective of this study. Analysis of the results suggests that bifurcation of flows is effective in reducing the increment in pressure drop relative to heat transfer enhancement. Optimising the geometries of the Constructal fins is therefore the potential future study in achieving a bigger stride in energy efficiency at much lower costs.

Keywords: constructal theory, enhanced heat transfer, microchannel, pressure drop

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392 High-Performance Thin-layer Chromatography (HPTLC) Analysis of Multi-Ingredient Traditional Chinese Medicine Supplement

Authors: Martin Cai, Khadijah B. Hashim, Leng Leo, Edmund F. Tian

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Analysis of traditional Chinese medicinal (TCM) supplements has always been a laborious task, particularly in the case of multi‐ingredient formulations. Traditionally, herbal extracts are analysed using one or few markers compounds. In the recent years, however, pharmaceutical companies are introducing health supplements of TCM active ingredients to cater to the needs of consumers in the fast-paced society in this age. As such, new problems arise in the aspects of composition identification as well as quality analysis. In most cases of products or supplements formulated with multiple TCM herbs, the chemical composition, and nature of each raw material differs greatly from the others in the formulation. This results in a requirement for individual analytical processes in order to identify the marker compounds in the various botanicals. Thin-layer Chromatography (TLC) is a simple, cost effective, yet well-regarded method for the analysis of natural products, both as a Pharmacopeia-approved method for identification and authentication of herbs, and a great analytical tool for the discovery of chemical compositions in herbal extracts. Recent technical advances introduced High-Performance TLC (HPTLC) where, with the help of automated equipment and improvements on the chromatographic materials, both the quality and reproducibility are greatly improved, allowing for highly standardised analysis with greater details. Here we report an industrial consultancy project with ONI Global Pte Ltd for the analysis of LAC Liver Protector, a TCM formulation aimed at improving liver health. The aim of this study was to identify 4 key components of the supplement using HPTLC, following protocols derived from Chinese Pharmacopeia standards. By comparing the TLC profiles of the supplement to the extracts of the herbs reported in the label, this project proposes a simple and cost-effective analysis of the presence of the 4 marker compounds in the multi‐ingredient formulation by using 4 different HPTLC methods. With the increasing trend of small and medium-sized enterprises (SMEs) bringing natural products and health supplements into the market, it is crucial that the qualities of both raw materials and end products be well-assured for the protection of consumers. With the technology of HPTLC, science can be incorporated to help SMEs with their quality control, thereby ensuring product quality.

Keywords: traditional Chinese medicine supplement, high performance thin layer chromatography, active ingredients, product quality

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391 An Investigation of Peptide Functionalized Gold Nanoparticles On Colon Cancer Cells For Biomedical Application

Authors: Rolivhuwa Bishop Ramagoma1*, Lynn Cairncross1, , Saartjie Roux1

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According to the world health organisation, colon cancer is among the most common cancers diagnosed in both men and women. Specifically, it is the second leading cause of cancer related deaths accounting for over 860 000 deaths worldwide in 2018. Currently, chemotherapy has become an essential component of most cancer treatments. Despite progress in cancer drug development over the previous years, traditional chemotherapeutic drugs still have low selectivity for targeting tumour tissues and are frequently constrained by dose-limiting toxicity. The creation of nanoscale delivery vehicles capable of directly directing treatment into cancer cells has recently caught the interest of researchers. Herein, the development of peptide-functionalized polyethylene glycol gold nanoparticles (Peptide-PEG-AuNPs) as a cellular probe and delivery agent is described, with the higher aim to develop a specific diagnostic prototype and assess their specificity not only against cell lines but primary human cells as well. Gold nanoparticles (AuNPs) were synthesized and stabilized through chemical conjugation. The synthesized AuNPs were characterized, stability in physiological solutions was assessed, their cytotoxicity against colon carcinoma and non-carcinoma skin fibroblasts was also studied. Furthermore, genetic effect through real-time polymerase chain reaction (RT-PCR), localization and uptake, peptide specificity were also determined. In this study, different peptide-AuNPs were found to have preferential toxicity at higher concentrations, as revealed by cell viability assays, however, all AuNPs presented immaculate stability for over 3 months following the method of synthesis. The final obtained peptide-PEG-AuNP conjugates showed good biocompatibility in the presence of high ionic solutions and biological media and good cellular uptake. Formulation of colon cancer specific targeting peptide was successful, additionally, the genes/pathways affected by the treatments were determined through RT-PCR. Primary cells study is still on going with promising results thus far.

Keywords: nanotechnology, cancer, diagnosis, therapeutics, gold nanoparticles.

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390 Towards Learning Query Expansion

Authors: Ahlem Bouziri, Chiraz Latiri, Eric Gaussier

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The steady growth in the size of textual document collections is a key progress-driver for modern information retrieval techniques whose effectiveness and efficiency are constantly challenged. Given a user query, the number of retrieved documents can be overwhelmingly large, hampering their efficient exploitation by the user. In addition, retaining only relevant documents in a query answer is of paramount importance for an effective meeting of the user needs. In this situation, the query expansion technique offers an interesting solution for obtaining a complete answer while preserving the quality of retained documents. This mainly relies on an accurate choice of the added terms to an initial query. Interestingly enough, query expansion takes advantage of large text volumes by extracting statistical information about index terms co-occurrences and using it to make user queries better fit the real information needs. In this respect, a promising track consists in the application of data mining methods to extract dependencies between terms, namely a generic basis of association rules between terms. The key feature of our approach is a better trade off between the size of the mining result and the conveyed knowledge. Thus, face to the huge number of derived association rules and in order to select the optimal combination of query terms from the generic basis, we propose to model the problem as a classification problem and solve it using a supervised learning algorithm such as SVM or k-means. For this purpose, we first generate a training set using a genetic algorithm based approach that explores the association rules space in order to find an optimal set of expansion terms, improving the MAP of the search results. The experiments were performed on SDA 95 collection, a data collection for information retrieval. It was found that the results were better in both terms of MAP and NDCG. The main observation is that the hybridization of text mining techniques and query expansion in an intelligent way allows us to incorporate the good features of all of them. As this is a preliminary attempt in this direction, there is a large scope for enhancing the proposed method.

Keywords: supervised leaning, classification, query expansion, association rules

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389 TP53 Mutations in Molecular Subtypes of Breast Cancer in Young Pakistani Patients

Authors: Nadia Naseem, Farwa Batool, Nasir Mehmood, AbdulHannan Nagi

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Background: The incidence and mortality of breast cancer vary significantly in geographically distinct populations. In Pakistan, breast cancer has shown an increase in incidence in young females and is characterized by more aggressive behavior. The tumor suppressor TP53 gene is a crucial genetic factor that plays a significant role in breast carcinogenesis. This study investigated the TP53 mutations in molecular subtypes of both nodes negative and positive breast cancer in young Pakistani patients. Material and Methods: p53, Estrogen Receptor (ER), Progesterone Receptor (PR), Her-2 neu and Ki 67 expressions were analyzed immunohistochemically in a series of 75 node negative (A) and 75 node positive (B) young (aged: 19-40 years) breast cancer patients diagnosed between 2014 to 2017 at two leading hospitals of Punjab, Pakistan. Tumor tissue specimens and peripheral blood samples were examined for TP53 mutations by direct sequencing of the gene (exons 4-9). The relation of TP53 mutations to these markers and clinicopathological data was investigated. Results: Mean age of the patients was 32.4 + 9.1 SD. Invasive breast carcinoma was the most frequent histological variant (A=92%, B=94.6%). Grade 3 carcinoma was the commonest grade (A=72%, B=81.3%). Triple negative cases (ER-, PR-, Her-2) formed most of the molecular subtypes (A=44%, B=50.6%). A total of 17.2% (A: 6.6%, B: 10.6%) patients showed TP53 mutations. Mutations were significantly more frequent in triple negative cases (A: 74.8%, B: 62.2%) compared to HER2-positive patients (P < 0.0001). In the multivariate analysis of the whole patient group, the independent prognosticator were triple negative cases (P=0.021), TP53 overexpression by IHC (P=0.001) and advanced-stage disease (P=0.007). No statistically significant correlation between TP53 mutations and clinicopathological parameters was found (P < 0.05). Conclusions: It is concluded that TP53 mutations are infrequently present in breast carcinoma of young Pakistani population and there was no significant correlation between p53 mutation and early onset disease. Immunohistochemically detected TP53 expression in our resource-constrained to set up can be beneficial in predicting mutations at the younger age in our population.

Keywords: immunohistochemistry (IHC), invasive breast carcinoma (IBC), Pakistan, TP53

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388 Evaluation of Occupational Doses in Interventional Radiology

Authors: Fernando Antonio Bacchim Neto, Allan Felipe Fattori Alves, Maria Eugênia Dela Rosa, Regina Moura, Diana Rodrigues De Pina

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Interventional Radiology is the radiology modality that provides the highest dose values to medical staff. Recent researches show that personal dosimeters may underestimate dose values in interventional physicians, especially in extremities (hands and feet) and eye lens. The aim of this work was to study radiation exposure levels of medical staff in different interventional radiology procedures and estimate the annual maximum numbers of procedures (AMN) that each physician could perform without exceed the annual limits of dose established by normative. For this purpose LiF:Mg,Ti (TLD-100) dosimeters were positioned in different body regions of the interventional physician (eye lens, thyroid, chest, gonads, hand and foot) above the radiological protection vests as lead apron and thyroid shield. Attenuation values for lead protection vests were based on international guidelines. Based on these data were chosen as 90% attenuation of the lead vests and 60% attenuation of the protective glasses. 25 procedures were evaluated: 10 diagnostics, 10 angioplasty, and 5-aneurysm treatment. The AMN of diagnostic procedures was 641 for the primary interventional radiologist and 930 for the assisting interventional radiologist. For the angioplasty procedures, the AMN for primary interventional radiologist was 445 and for assisting interventional radiologist was 1202. As for the procedures of aneurism treatment, the AMN for the primary interventional radiologist was 113 and for the assisting interventional radiologist were 215. All AMN were limited by the eye lens doses already considering the use of protective glasses. In all categories evaluated, the higher dose values are found in gonads and in the lower regions of professionals, both for the primary interventionist and for the assisting, but the eyes lens dose limits are smaller than these regions. Additional protections as mobile barriers, which can be positioned between the interventionist and the patient, can decrease the exposures in the eye lens, providing a greater protection for the medical staff. The alternation of professionals to perform each type of procedure can reduce the dose values received by them over a period. The analysis of dose profiles proposed in this work showed that personal dosimeters positioned in chest might underestimate dose values in other body parts of the interventional physician, especially in extremities and eye lens. As each body region of the interventionist is subject to different levels of exposure, dose distribution in each region provides a better approach to what actions are necessary to ensure the radiological protection of medical staff.

Keywords: interventional radiology, radiation protection, occupationally exposed individual, hemodynamic

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387 Krill-Herd Step-Up Approach Based Energy Efficiency Enhancement Opportunities in the Offshore Mixed Refrigerant Natural Gas Liquefaction Process

Authors: Kinza Qadeer, Muhammad Abdul Qyyum, Moonyong Lee

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Natural gas has become an attractive energy source in comparison with other fossil fuels because of its lower CO₂ and other air pollutant emissions. Therefore, compared to the demand for coal and oil, that for natural gas is increasing rapidly world-wide. The transportation of natural gas over long distances as a liquid (LNG) preferable for several reasons, including economic, technical, political, and safety factors. However, LNG production is an energy-intensive process due to the tremendous amount of power requirements for compression of refrigerants, which provide sufficient cold energy to liquefy natural gas. Therefore, one of the major issues in the LNG industry is to improve the energy efficiency of existing LNG processes through a cost-effective approach that is 'optimization'. In this context, a bio-inspired Krill-herd (KH) step-up approach was examined to enhance the energy efficiency of a single mixed refrigerant (SMR) natural gas liquefaction (LNG) process, which is considered as a most promising candidate for offshore LNG production (FPSO). The optimal design of a natural gas liquefaction processes involves multivariable non-linear thermodynamic interactions, which lead to exergy destruction and contribute to process irreversibility. As key decision variables, the optimal values of mixed refrigerant flow rates and process operating pressures were determined based on the herding behavior of krill individuals corresponding to the minimum energy consumption for LNG production. To perform the rigorous process analysis, the SMR process was simulated in Aspen Hysys® software and the resulting model was connected with the Krill-herd approach coded in MATLAB. The optimal operating conditions found by the proposed approach significantly reduced the overall energy consumption of the SMR process by ≤ 22.5% and also improved the coefficient of performance in comparison with the base case. The proposed approach was also compared with other well-proven optimization algorithms, such as genetic and particle swarm optimization algorithms, and was found to exhibit a superior performance over these existing approaches.

Keywords: energy efficiency, Krill-herd, LNG, optimization, single mixed refrigerant

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386 Velma-ARC’s Rehabilitation of Repentant Cybercriminals in Nigeria

Authors: Umukoro Omonigho Simon, Ashaolu David ‘Diya, Aroyewun-Olaleye Temitope Folashade

Abstract:

The VELMA Action to Reduce Cybercrime (ARC) is an initiative, the first of its kind in Nigeria, designed to identify, rehabilitate and empower repentant cybercrime offenders popularly known as ‘yahoo boys’ in Nigerian parlance. Velma ARC provides social inclusion boot camps with the goal of rehabilitating cybercriminals via psychotherapeutic interventions, improving their IT skills, and empowering them to make constructive contributions to society. This report highlights the psychological interventions provided for participants of the maiden edition of the Velma ARC boot camp and presents the outcomes of these interventions. The boot camp was set up in a hotel premises which was booked solely for the 1 month event. The participants were selected and invited via the Velma online recruitment portal based on an objective double-blind selection process from a pool of potential participants who signified interest via the registration portal. The participants were first taken through psychological profiling (personality, symptomology and psychopathology) before the individual and group sessions began. They were profiled using the Minnesota Multiphasic Personality Inventory -2- Restructured Form (MMPI-2-RF), the latest version of its series. Individual psychotherapy sessions were conducted for all participants based on what was interpreted on their profiles. Focus group discussion was held later to discuss a movie titled ‘catch me if you can’ directed by Steven Spielberg, featuring Leonardo De Caprio and Tom Hanks. The movie was based on the true life story of Frank Abagnale, who was a notorious scammer and con artist in his youthful years. Emergent themes from the movie were discussed as psycho-educative parameters for the participants. The overall evaluation of outcomes from the VELMA ARC rehabilitation boot camp stemmed from a disaggregated assessment of observed changes which are summarized in the final report of the clinical psychologist and was detailed enough to infer genuine repentance and positive change in attitude towards cybercrime among the participants. Follow up services were incorporated to validate initial observations. This gives credence to the potency of the psycho-educative intervention provided during the Velma ARC boot camp. It was recommended that support and collaborations from the government and other agencies/individuals would assist the VELMA foundation in expanding the scope and quality of the Velma ARC initiative as an additional requirement for cybercrime offenders following incarceration.

Keywords: Velma-ARC, cybercrime offenders, rehabilitation, Nigeria

Procedia PDF Downloads 126
385 Phenotype Prediction of DNA Sequence Data: A Machine and Statistical Learning Approach

Authors: Mpho Mokoatle, Darlington Mapiye, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on $k$-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0%, 80.5%, 80.5%, 63.6%, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms.

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

Procedia PDF Downloads 140
384 Phenotype Prediction of DNA Sequence Data: A Machine and Statistical Learning Approach

Authors: Darlington Mapiye, Mpho Mokoatle, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on k-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0 %, 80.5 %, 80.5 %, 63.6 %, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

Procedia PDF Downloads 128
383 Isolation, Identification and Screening of Marine Fungi for Potential Tyrosinase Inhibitor, Antibacterial and Antioxidant for Future Cosmeceuticals

Authors: Shivankar Agrawal, Sunil Kumar Deshmukh, Colin Barrow, Alok Adholeya

Abstract:

A variety of genetic and environmental factors cause various cosmetics and dermatological problems. There are already claimed drugs available in market for treating these problems. However, the challenge remains in finding more potent, environmental friendly, causing minimal side effects and economical cosmeceuticals. This leads to an increased demand for natural cosmeceutical products in the last few decades. Plant derived ingredients are limited because plants either contain toxic metabolites, grow too slow or seasonal harvesting is a problem. To identify new bioactive cosmetics ingredients of marine microbial bioresource, we screened 35 marine fungi isolated from marine samples collected from Andaman Island and west coast of India. Fungal crude extracts were investigated for their antityrosinase, antioxidant and antibacterial activities for the purpose of identifying anti-aging, skin-whitening and anti-acne biomolecule with the potential in cosmetics. In the tyrosinase inhibition and 2, 2-Diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assays, two fungal extracts, including “P2”, Talaromyces stipitatus and “D4”, Aspergillus terreus showed high inhibitory activity at 1mg/mL for tyrosinase inhibition and 0.5mg/mL for DPPH scavenging. The in vitro antimicrobial activity was investigated by the agar well diffusion method. In the tyrosinase inhibition assay, 8 extracts showed significant antibacterial activity against bacteria causing skin and wound infection in humans. In the course of systematic screening program for bioactive marine fungi, strain “D5” was found to be most potent strain with MIC value of 1mg/mL, which was morphologically identified as Simplicillium lamellicola. The effects of the most active crude extracts against their susceptible test microorganisms were also investigated by SEM analysis. Further investigations will focus on purification and characterization major active components responsible for these activities.

Keywords: antioxidant, antimicrobial activity, tyrosinase, cosmeceuticals, marine fungi

Procedia PDF Downloads 258
382 The Revival of Cultural Heritage through Social Space Upliftment: Case Study of the Walled City of Ajmer, India

Authors: Vaishali Sharma

Abstract:

The research is an attempt to hunt a scientific and objective method to transform Ajmer's traditional walled city into a living cultural heritage space, exploring urban management methods to elevate local economy and social space in relation to specific cultural-based initiatives. Ajmer is among the oldest and religiously diverse settlements in Rajasthan, that has seen superimposed developments through the eras. With numerous agencies operating towards the development of the town core of Ajmer, it becomes essential to structure development changes in tune with the transformations and the existing heritage. The study was radio-controlled by the subsequent analysis question: What is the way to overcome the genetic social and economic stress inside the communities and revive public life? In order to create necessary interventions at the neighbourhood level, fifteen neighbourhoods were identified. Each of those was analyzed relatively on three major dimensions: Heritage, Social and Local Economy. Each dimension was further broken down into multiple sub-aspects for an overall and exhaustive understanding. The average median values of the responses were used to develop a color-coded matrix to represent the scores in an exceedingly structured quantified manner, moreover, linking it to the spatial structure. Respondent perceptions on numerous dimensions were additionally recorded, so that the proposals are inclusive in nature. The goals are targeted at Ajmer's traditional walled towns, which will make it easier for the community to regulate the rapid transformations and commercialization occurring within the space. The study recommends the necessity for accrued support in methods and policies from the non-public sector, businesses as well as local stakeholders. An expansion, revitalization and maintenance of the major business and heritage corridors, for an increased local and visitor experience, can produce an impetus for promotion of the intangible heritage, to spur the local economic processes, conservation of heritage precincts and upward development.

Keywords: cultural heritage, economic revitalization, neighbourhoods in walled cities, social space, tangible and intangible heritage

Procedia PDF Downloads 132
381 Development of Structural Deterioration Models for Flexible Pavement Using Traffic Speed Deflectometer Data

Authors: Sittampalam Manoharan, Gary Chai, Sanaul Chowdhury, Andrew Golding

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The primary objective of this paper is to present a simplified approach to develop the structural deterioration model using traffic speed deflectometer data for flexible pavements. Maintaining assets to meet functional performance is not economical or sustainable in the long terms, and it would end up needing much more investments for road agencies and extra costs for road users. Performance models have to be included for structural and functional predicting capabilities, in order to assess the needs, and the time frame of those needs. As such structural modelling plays a vital role in the prediction of pavement performance. A structural condition is important for the prediction of remaining life and overall health of a road network and also major influence on the valuation of road pavement. Therefore, the structural deterioration model is a critical input into pavement management system for predicting pavement rehabilitation needs accurately. The Traffic Speed Deflectometer (TSD) is a vehicle-mounted Doppler laser system that is capable of continuously measuring the structural bearing capacity of a pavement whilst moving at traffic speeds. The device’s high accuracy, high speed, and continuous deflection profiles are useful for network-level applications such as predicting road rehabilitations needs and remaining structural service life. The methodology adopted in this model by utilizing time series TSD maximum deflection (D0) data in conjunction with rutting, rutting progression, pavement age, subgrade strength and equivalent standard axle (ESA) data. Then, regression analyses were undertaken to establish a correlation equation of structural deterioration as a function of rutting, pavement age, seal age and equivalent standard axle (ESA). This study developed a simple structural deterioration model which will enable to incorporate available TSD structural data in pavement management system for developing network-level pavement investment strategies. Therefore, the available funding can be used effectively to minimize the whole –of- life cost of the road asset and also improve pavement performance. This study will contribute to narrowing the knowledge gap in structural data usage in network level investment analysis and provide a simple methodology to use structural data effectively in investment decision-making process for road agencies to manage aging road assets.

Keywords: adjusted structural number (SNP), maximum deflection (D0), equant standard axle (ESA), traffic speed deflectometer (TSD)

Procedia PDF Downloads 132
380 Study of Relation between P53 and Mir-146a Rs2910164 Polymorphism in Cervical Lesion

Authors: Hossein Rassi, Marjan Moradi Fard, Masoud Houshmand

Abstract:

Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human papillomavirus (HPV) infection is the leading risk factor for cervical intraepithelial neoplasia(CIN)and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33 and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, p53, miR-146a, rs2910164, polymorphism

Procedia PDF Downloads 449
379 Investigation p53 and miR-146a rs2910164 Polymorphism in Cervical Lesion

Authors: Hossein Rassi, Marjan Moradi fard, Masoud Houshmand

Abstract:

Background: Cervical cancer is multistep disease that is thought to result from an interaction between genetic background and environmental factors. Human Papillomavirus (HPV) infection is the leading risk factor for Cervical Intraepithelial Neoplasia (CIN) and cervical cancer. In other hand, some of p53 and miRNA polymorphism may plays an important role in carcinogenesis. This study attempts to clarify the relation of p53 genotypes and miR-146a rs2910164 polymorphism in cervical lesions. Method: Forty two archival samples with cervical lesion retired from Khatam hospital and 40 sample from healthy persons used as control group. A simple and rapid method was used to detect the simultaneous amplification of the HPV consensus L1 region and HPV-16,-18, -11, -31, 33, and -35 along with the b-globin gene as an internal control. We use Multiplex PCR for detection of P53 and miR-146a rs2910164 genotypes in our lab. Finally, data analysis was performed using the 7 version of the Epi Info(TM) 2012 software and test chi-square(x2) for trend. Results: Cervix lesions were collected from 42 patients with Squamous metaplasia, cervical intraepithelial neoplasia, and cervical carcinoma. Successful DNA extraction was assessed by PCR amplification of b-actin gene (99 bp). According to the results, p53 GG genotype and miR-146a rs2910164 CC genotype was significantly associated with increased risk of cervical lesions in the study population. In this study, we detected 13 HPV 18 from 42 cervical cancer. Conclusion: The connection between several SNP polymorphism and human virus papilloma in rare researches were seen. The reason of these differences in researches' findings can result in different kinds of races and geographic situations and also differences in life grooves in every region. The present study provided preliminary evidence that a p53 GG genotype and miR-146a rs2910164 CC genotype may effect cervical cancer risk in the study population, interacting synergistically with HPV 18 genotype. Our results demonstrate that the testing of p53 codon 72 polymorphism genotypes and miR-146a rs2910164 polymorphism genotypes in combination with HPV18 can serve as major risk factors in the early identification of cervical cancers. Furthermore, the results indicate the possibility of primary prevention of cervical cancer by vaccination against HPV18 in Iran.

Keywords: cervical cancer, miR-146a rs2910164 polymorphism, p53 polymorphism, intraepithelial, neoplasia, HPV

Procedia PDF Downloads 380
378 Mutations in rpoB, katG and inhA Genes: The Association with Resistance to Rifampicin and Isoniazid in Egyptian Mycobacterium tuberculosis Clinical Isolates

Authors: Ayman K. El Essawy, Amal M. Hosny, Hala M. Abu Shady

Abstract:

The rapid detection of TB and drug resistance, both optimizes treatment and improves outcomes. In the current study, respiratory specimens were collected from 155 patients. Conventional susceptibility testing and MIC determination were performed for rifampicin (RIF) and isoniazid (INH). Genotype MTBDRplus assay, which is a molecular genetic assay based on the DNA-STRIP technology and specific gene sequencing with primers for rpoB, KatG, and mab-inhA genes were used to detect mutations associated with resistance to rifampicin and isoniazid. In comparison to other categories, most of rifampicin resistant (61.5%) and isoniazid resistant isolates (47.1%) were from patients relapsed in treatment. The genotypic profile (using Genotype MTBDRplus assay) of multi-drug resistant (MDR) isolates showed missing of katG wild type 1 (WT1) band and appearance of mutation band katG MUT2. For isoniazid mono-resistant isolates, 80% showed katG MUT1, 20% showed katG MUT1, and inhA MUT1, 20% showed only inhA MUT1. Accordingly, 100% of isoniazid resistant strains were detected by this assay. Out of 17 resistant strains, 16 had mutation bands for katG distinguished high resistance to isoniazid. The assay could clearly detect rifampicin resistance among 66.7% of MDR isolates that showed mutation band rpoB MUT3 while 33.3% of them were considered as unknown. One mono-resistant rifampicin isolate did not show rifampicin mutation bands by Genotype MTBDRplus assay, but it showed an unexpected mutation in Codon 531 of rpoB by DNA sequence analysis. Rifampicin resistance in this strain could be associated with a mutation in codon 531 of rpoB (based on molecular sequencing), and Genotype MTBDRplus assay could not detect the associated mutation. If the results of Genotype MTBDRplus assay and sequencing were combined, this strain shows hetero-resistance pattern. Gene sequencing of eight selected isolates, previously tested by Genotype MTBDRplus assay, could detect resistance mutations mainly in codon 315 (katG gene), position -15 in inhA promotes gene for isoniazid resistance and codon 531 (rpoB gene) for rifampicin resistance. Genotyping techniques allow distinguishing between recurrent cases of reinfection or reactivation and supports epidemiological studies.

Keywords: M. tuberculosis, rpoB, KatG, inhA, genotype MTBDRplus

Procedia PDF Downloads 134
377 Impact of CYP3A5 Polymorphism on Tacrolimus to Predict the Optimal Initial Dose Requirements in South Indian Renal Transplant Recipients

Authors: S. Sreeja, Radhakrishnan R. Nair, Noble Gracious, Sreeja S. Nair, M. Radhakrishna Pillai

Abstract:

Background: Tacrolimus is a potent immunosuppressant clinically used for the long term treatment of antirejection of transplanted organs in liver and kidney transplant recipients though dose optimization is poorly managed. However, So far no study has been carried out on the South Indian kidney transplant patients. The objective of this study is to evaluate the potential influence of a functional polymorphism in CYP3A5*3 gene on tacrolimus physiological availability/dose ratio in South Indian renal transplant patients. Materials and Methods: Twenty five renal transplant recipients receiving tacrolimus were enrolled in this study. Their body weight, drug dosage, and therapeutic concentration of Tacrolimus were observed. All patients were on standard immunosuppressive regime of Tacrolimus-Mycophenolate mofetil along with steroids on a starting dose of Tac 0.1 mg/kg/day. CYP3A5 genotyping was performed by PCR followed with RFLP. Conformation of RFLP analysis and variation in the nucleotide sequence of CYP3A5*3 gene were determined by direct sequencing using a validated automated generic analyzer. Results: A significant association was found between tacrolimus per dose/kg/d and CYP3A5 gene (A6986G) polymorphism in the study population. The CYP3A5 *1/*1, *1/*3 and *3/*3 genotypes were detected in 5 (20 %), 5 (20 %) and 15 (60 %) of the 25 graft recipients, respectively. CYP3A5*3 genotypes were found to be a good predictor of tacrolimus Concentration/Dose ratio in kidney transplant recipients. Significantly higher L/D was observed among non-expressors 9.483 ng/mL(4.5- 14.1) as compared with the expressors 5.154 ng/mL (4.42-6.5 ) of CYP3A5. Acute rejection episodes were significantly higher for CYP3A5*1 homozygotes compared to patients with CYP3A5*1/*3 and CYP3A5*3/*3 genotypes (40 % versus 20 % and 13 %, respectively ). The dose normalized TAC concentration (ng/ml/mg/kg) was significantly lower in patients having CYP3A5*1/*3 polymorphism. Conclusion: This is the first study to extensively determine the effect of CYP3A5*3 genetic polymorphism on tacrolimus pharmacokinetics in South Indian renal transplant recipients and also shows that majority of our patients carry mutant allele A6986G in CYP3A5*3 gene. Identification of CYP3A5 polymorphism prior to transplantation could contribute to evaluate the appropriate initial dosage of tacrolimus for each patient.

Keywords: kidney transplant patients, CYP3A5 genotype, tacrolimus, RFLP

Procedia PDF Downloads 278
376 Role of Maternal Astaxanthin Supplementation on Brain Derived Neurotrophic Factor and Spatial Learning Behavior in Wistar Rat Offspring’s

Authors: K. M. Damodara Gowda

Abstract:

Background: Maternal health and nutrition are considered as the predominant factors influencing brain functional development. If the mother is free of illness and genetic defects, maternal nutrition would be one of the most critical factors affecting the brain development. Calorie restrictions cause significant impairment in spatial learning ability and the levels of Brain Derived Neurotrophic Factor (BDNF) in rats. But, the mechanism by which the prenatal under-nutrition leads to impairment in brain learning and memory function is still unclear. In the present study, prenatal Astaxanthin supplementation on BDNF level, spatial learning and memory performance in the offspring’s of normal, calorie restricted and Astaxanthin supplemented rats was investigated. Methodology: The rats were administered with 6mg and 12 mg of astaxanthin /kg bw for 21 days following which acquisition and retention of spatial memory was tested in a partially-baited eight arm radial maze. The BDNF level in different regions of the brain (cerebral cortex, hippocampus and cerebellum) was estimated by ELISA method. Results: Calorie restricted animals treated with astaxanthin made significantly more correct choices (P < 0.05), and fewer reference memory errors (P < 0.05) on the tenth day of training compared to offsprings of calorie restricted animals. Calorie restricted animals treated with astaxanthin also made significantly higher correct choices (P < 0.001) than untreated calorie restricted animals in a retention test 10 days after the training period. The mean BDNF level in cerebral cortex, Hippocampus and cerebellum in Calorie restricted animals treated with astaxanthin didnot show significant variation from that of control animals. Conclusion: Findings of the study indicated that memory and learning was impaired in the offspring’s of calorie restricted rats which was effectively modulated by astaxanthin at the dosage of 12 mg/kg body weight. In the same way the BDNF level at cerebral cortex, Hippocampus and Cerebellum was also declined in the offspring’s of calorie restricted animals, which was also found to be effectively normalized by astaxanthin.

Keywords: calorie restiction, learning, Memory, Cerebral cortex, Hippocampus, Cerebellum, BDNF, Astaxanthin

Procedia PDF Downloads 213
375 Therapeutic Effects of Guar Gum Nanoparticles in Oxazolone-Induced Atopic Dermatitis

Authors: Nandita Ghosh, Shinjini Mitra, Ena Ray Banerjee

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Atopic dermatitis (AD) is a chronic disease of the skin, involving itchy, reddish, and scaly lesions. It mainly affects children and has a high prevalence in developing countries. The AD may occur due to environmental or genetic factors. There is no permanent cure for the AD. Currently, all therapeutic strategies involve methods to simply alleviate the symptoms, and include lotions and corticosteroids, which have adverse effects. Use of phytochemicals and natural products has not yet been exploited fully. The particle used in this study is derived from Cyamopsis tetragonoloba, an edible polysaccharide with a galactomannan component. The mannose component mainly increases its specificity towards cellular uptake by mannose receptors, highly expressed by the macrophage. The aim of this study was to determine the therapeutic effect of guar gum nanoparticles (GN) in vitro and in vivo in the AD. To assess the wound healing capacity of the guar gum nanoparticle (GN), we first treated adherent NIH3T3 cells, with a scratch injury, with GN. GN successfully healed the wound caused by the scratch. In the in vivo experiment, Balb/c mice ear were topically treated with oxazolone (oxa) to induce AD and then were topically treated with GN. The ear thickness was increased significantly till day 28 on the treatment of Oxa. The GN application showed a significant decrease in the thickness as assessed on day 28. The total cell count of skin cells showed fold increase when treated with oxa, was again decreased on topical application of GN on the affected skin. The eosinophil count, as assessed by Giemsa staining was also increased when treated with oxa, GN application led to a significant decrease. The IgE level was assessed in the serum samples which showed that GN helped in restoring the alleviated IgE level. The T helper cells and the macrophage population showed increased percentage when treated with oxa, the GN application. This was examined by flow cytometry. The H&E staining of the ear tissue showed epidermal thickness in the oxa treated mice, GN application showed reduced cellular filtration followed by epidermal thickness. Thus our assays showed that GN was successful in alleviating the disease caused by Oxa when administered topically.

Keywords: allergen, inflammation, nanodrug, wound

Procedia PDF Downloads 221
374 Maternal Exposure to Bisphenol A and Its Association with Birth Outcomes

Authors: Yi-Ting Chen, Yu-Fang Huang, Pei-Wei Wang, Hai-Wei Liang, Chun-Hao Lai, Mei-Lien Chen

Abstract:

Background: Bisphenol A (BPA) is commonly used in consumer products, such as inner coatings of cans and polycarbonated bottles. BPA is considered to be an endocrine disrupting substance (EDs) that affects normal human hormones and may cause adverse effects on human health. Pregnant women and fetuses are susceptible groups of endocrine disrupting substances. Prenatal exposure to BPA has been shown to affect the fetus through the placenta. Therefore, it is important to evaluate the potential health risk of fetal exposure to BPA during pregnancy. The aims of this study were (1) to determine the urinary concentration of BPA in pregnant women, and (2) to investigate the association between BPA exposure during pregnancy and birth outcomes. Methods: This study recruited 117 pregnant women and their fetuses from 2012 to 2014 from the Taiwan Maternal- Infant Cohort Study (TMICS). Maternal urine samples were collected in the third trimester and questionnaires were used to collect socio-demographic characteristics, eating habits and medical conditions of the participants. Information about birth outcomes of the fetus was obtained from medical records. As for chemicals analysis, BPA concentrations in urine were determined by off-line solid-phase extraction-ultra-performance liquid chromatography coupled with a Q-Tof mass spectrometer. The urinary concentrations were adjusted with creatinine. The association between maternal concentrations of BPA and birth outcomes was estimated using the logistic regression model. Results: The detection rate of BPA is 99%; the concentration ranges (μg/g) from 0.16 to 46.90. The mean (SD) BPA levels are 5.37(6.42) μg/g creatinine. The mean ±SD of the body weight, body length, head circumference, chest circumference and gestational age at birth are 3105.18 ± 339.53 g, 49.33 ± 1.90 cm, 34.16 ± 1.06 cm, 32.34 ± 1.37 cm and 38.58 ± 1.37 weeks, respectively. After stratifying the exposure levels into two groups by median, pregnant women in higher exposure group would have an increased risk of lower body weight (OR=0.57, 95%CI=0.271-1.193), smaller chest circumference (OR=0.70, 95%CI=0.335-1.47) and shorter gestational age at birth newborn (OR=0.46, 95%CI=0.191-1.114). However, there are no associations between BPA concentration and birth outcomes reach a significant level (p < 0.05) in statistics. Conclusions: This study presents prenatal BPA profiles and infants in northern Taiwan. Women who have higher BPA concentrations tend to give birth to lower body weight, smaller chest circumference or shorter gestational age at birth newborn. More data will be included to verify the results. This report will also present the predictors of BPA concentrations for pregnant women.

Keywords: bisphenol A, birth outcomes, biomonitoring, prenatal exposure

Procedia PDF Downloads 112
373 Biological Control of Fusarium Crown and Root and Tomato (Solanum lycopersicum L.) Growth Promotion Using Endophytic Fungi from Withania somnifera L.

Authors: Nefzi Ahlem, Aydi Ben Abdallah Rania, Jabnoun-Khiareddine Hayfa, Ammar Nawaim, Mejda Daami-Remadi

Abstract:

Fusarium Crown and Root Rot (FCRR) caused by Fusarium oxysporum f. sp. radicis-lycopersici (FORL) is a serious tomato (Solanum lycopersicum L.) disease in Tunisia. Its management is very difficult due to the long survival of its resting structures and to the luck of genetic resistance. In this work, we explored the wild Solanaceae species Withania somnifera, growing in the Tunisian Centre-East, as a potential source of biocontrol agents effective in FCRR suppression and tomato growth promotion. Seven fungal isolates were shown able to colonize tomato roots, crowns, and stems. Used as conidial suspensions or cell-free culture filtrates, all tested fungal treatments significantly enhanced tomato growth parameters by 21.5-90.3% over FORL-free control and by 27.6-93.5% over pathogen-inoculated control. All treatments significantly decreased the leaf and root damage index by 28.5-92.8 and the vascular browning extent 9.7-86.4% over FORL-inoculated and untreated control. The highest disease suppression ability (decrease by 86.4-92.8% in FCRR severity) over pathogen-inoculated control and by 81.3-88.8 over hymexazol-treated control) was expressed by I6 based treatments. This endophytic fungus was morphologically characterized and identified using rDNA sequencing gene as Fusarium sp. I6 (MG835371). This fungus was shown able to reduce FORL radial growth by 58.5–83.2% using its conidial suspension or cell-free culture filtrate. Fusarium sp. I6 showed chitinolytic, proteolytic and amylase activities. The current study clearly demonstrated that Fusarium sp. (I6) is a promising biocontrol candidate for suppressing FCRR severity and promoting tomato growth. Further investigations are required for elucidating its mechanism of action involved in disease suppression and plant growth promotion.

Keywords: antifungal activity, associated fungi, Fusarium oxysporum f. sp. radicis-lycopersici, Withania somnifera, tomato growth

Procedia PDF Downloads 125
372 Association between a Serotonin Re-Uptake Transporter Gene Polymorphism and Mucosal Serotonin Level in Women Patients with Irritable Bowel Syndrome and Healthy Control: A Pilot Study from Northern India

Authors: Sunil Kumar, Uday C. Ghoshal

Abstract:

Background and aims: Serotonin (5-hydroxtryptamine, 5-HT) is an important factor in gut function, playing key roles in intestinal peristalsis and secretion, and in sensory signaling in the brain-gut axis. Removal from its sites of action is mediated by a specific protein called the serotonin reuptake transporter (SERT). Polymorphisms in the promoter region of the SERT gene have effects on transcriptional activity, resulting in altered 5-HT reuptake efficiency. Functional polymorphisms may underlie disturbance in gut function in individuals suffering with disorders such as irritable bowel syndrome (IBS). The aim of this study was to assess the potential association between SERT polymorphisms and the diarrhea predominant IBS (D-IBS) phenotype Subjects: A total of 36 northern Indian female patients and 55 female northern Indian healthy controls (HC) were subjected to genotyping. Methods: Leucocyte DNA of all subjects was analyzed by polymerase chain reaction based technologies for SERT polymorphisms, specifically the insertion/deletion polymorphism in the promoter (SERT-P). Statistical analysis was performed to assess association of SERT polymorphism allele with the D-IBS phenotype. Results: The frequency of distribution of SERT-P gene was comparable between female patients with IBS and HC (p = 0.086). However, frequency of SERT-P deletion/deletion genotype was significantly higher in female patients with D-IBS compared to C-IBS and A-IBS [17/19 (89.5%) vs. 4/12 (33.3%) vs. 1/5 (20%), p=0.001, respectively]. The mucosal level of serotonin was higher in D-IBS compared to C-IBS and A-IBS [Median, range (159.26, 98.78–212.1) vs. 110.4, 67.87–143.53 vs. 92.34, 78.8–166.3 pmol/mL, p=0.001, respectively]. The mucosal level of serotonin was higher in female patients with IBS with SERT-P deletion/deletion genotype compared deletion/insertion and insertion/insertion [157.65, 67.87–212.1 vs. 110.4, 78.1–143.32 vs. 100.5, 69.1–132.03 pmol/mL, p=0.001, respectively]. Patients with D-IBS with deletion/deletion genotype more often reported symptoms of abdominal pain, discomfort (p=0.025) and bloating (p=0.039). Symptoms development following lactose ingestion was strongly associated with D-IBS and SERT-P deletion/deletion genotype (p=0.004). Conclusions: Significant association was observed between D-IBS and the SERT-P deletion/deletion genotype, suggesting that the serotonin transporter is a potential candidate gene for D-IBS in women.

Keywords: serotonin, SERT, inflammatory bowel disease, genetic polymorphism

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371 Rare Diagnosis in Emergency Room: Moyamoya Disease

Authors: Ecem Deniz Kırkpantur, Ozge Ecmel Onur, Tuba Cimilli Ozturk, Ebru Unal Akoglu

Abstract:

Moyamoya disease is a unique chronic progressive cerebrovascular disease characterized by bilateral stenosis or occlusion of the arteries around the circle of Willis with prominent arterial collateral circulation. The occurrence of Moyamoya disease is related to immune, genetic and other factors. There is no curative treatment for Moyamoya disease. Secondary prevention for patients with symptomatic Moyamoya disease is largely centered on surgical revascularization techniques. We present here a 62-year old male presented with headache and vision loss for 2 days. He was previously diagnosed with hypertension and glaucoma. On physical examination, left eye movements were restricted medially, both eyes were hyperemic and their movements were painful. Other neurological and physical examination were normal. His vital signs and laboratory results were within normal limits. Computed tomography (CT) showed dilated vascular structures around both lateral ventricles and atherosclerotic changes inside the walls of internal carotid artery (ICA). Magnetic resonance imaging (MRI) and angiography (MRA) revealed dilated venous vascular structures around lateral ventricles and hyper-intense gliosis in periventricular white matter. Ischemic gliosis around the lateral ventricles were present in the Digital Subtracted Angiography (DSA). After the neurology, ophthalmology and neurosurgery consultation, the patient was diagnosed with Moyamoya disease, pulse steroid therapy was started for vision loss, and super-selective DSA was planned for further investigation. Moyamoya disease is a rare condition, but it can be an important cause of stroke in both children and adults. It generally affects anterior circulation, but posterior cerebral circulation may also be affected, as well. In the differential diagnosis of acute vision loss, occipital stroke related to Moyamoya disease should be considered. Direct and indirect surgical revascularization surgeries may be used to effectively revascularize affected brain areas, and have been shown to reduce risk of stroke.

Keywords: headache, Moyamoya disease, stroke, visual loss

Procedia PDF Downloads 247