Search results for: radiation therapy oncology group (RTOG)
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 10740

Search results for: radiation therapy oncology group (RTOG)

7320 Enhancing Neural Connections through Music and tDCS: Insights from an fNIRS Study

Authors: Dileep G., Akash Singh, Dalchand Ahirwar, Arkadeep Ghosh, Ashutosh Purohit, Gaurav Guleria, Kshatriya Om Prashant, Pushkar Patel, Saksham Kumar, Vanshaj Nathani, Vikas Dangi, Shubhajit Roy Chowdhury, Varun Dutt

Abstract:

Transcranial direct current stimulation (tDCS) has shown promise as a novel approach to enhance cognitive performance and provide therapeutic benefits for various brain disorders. However, the exact underlying brain mechanisms are not fully understood. We conducted a study to examine the brain's functional changes when subjected to simultaneous tDCS and music (Indian classical raga). During the study, participants in the experimental group underwent a 20-minute session of tDCS at two mA while listening to music (raga) for a duration of seven days. In contrast, the control group received a sham stimulation for two minutes at two mA over the same seven-day period. The objective was to examine whether repetitive tDCS could lead to the formation of additional functional connections between the medial prefrontal cortex (the stimulated area) and the auditory cortex in comparison to a sham stimulation group. In this study, 26 participants (5 female) underwent pre- and post-intervention scans, where changes were compared after one week of either tDCS or sham stimulation in conjunction with music. The study revealed significant effects of tDCS on functional connectivity between the stimulated area and the auditory cortex. The combination of tDCS applied over the mPFC and music resulted in newly formed connections. Based on our findings, it can be inferred that applying anodal tDCS over the mPFC enhances functional connectivity between the stimulated area and the auditory cortex when compared to the effects observed with sham stimulation.

Keywords: fNIRS, tDCS, neuroplasticity, music

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7319 Observation on Microbiological Profile of Type2 Diabetic Foot Ulcer and Its Antimicrobial Sensitivity Pattern in a Tertiary Care Hospital in Eastern India

Authors: Pampita Chakraborty, Sukumar Mukherjee

Abstract:

Diabetes Mellitus (DM) is commonly encountered metabolic disorder in clinical practice. An estimated 25 percent of DM patients develop foot problems. Foot ulceration and infection are one of the major causes of morbidity, hospitalization or even amputation. Objective: To isolate and identify bacterial pathogens in Diabetic Foot Ulcer (DFU) and to observe its antimicrobial sensitivity pattern. Methodology: A prospective study was conducted for a period of 9 months at the Department of Microbiology, GD Hospital & Diabetes Institute, Kolkata. 75 DFU patients were recruited in the study. Specimens for microbiological studies obtained from ulcer base were examined as gram stained smear and was cultured aerobically on Nutrient agar, Blood agar and MacConkey agar plates. Antimicrobial sensitivity test was performed by disc diffusion techniques according to CLSI guidelines. Result: In this study out of 75cases, 73% (55/75) were male and 27% (20/75) were females with mean (SD) age of 51.11(±10) years. Out of 75 pus cultures, 63(84%) showed growth of microorganism making total of 81 bacterial isolates with 71.42% of monomicrobial infection and 28.57% of polymicrobial infection. Out of 81 isolates 53(65.43%) were gram negative and 21(25.92%) were gram positive. E.coli was relatively common isolate 21(26%) followed by Staphylococcus aureus 15(18.5%), Klebsiella pneumonia 14(17.28%), Pseudomonas aeruginosa 12 (14.81%), Proteus spp. 3 (3.70%), and Enterococcus faecalis 6 (7.40%). 75% of Gram-negative microorganism were extended Beta-lactamase enzyme (ESBL) producer and around 20 % of Klebsiella and Proteus spp. were carbapenemase enzyme producer. Among Gram positive, around 50% of S.aureus was MRSA, sensitive only to Vancomycin, Teicoplanin & Linezolid. Conclusion: More prevalence of monomicrobial gram-negative bacteria than gram-positive bacteria in DFU was observed. This study emphasizes that Beta-Lactam group of antibiotics should not be the empirical treatment of choice for Gram-negative isolates; instead alternatives like Carbapenems, Amikacin could be a better option. On the other hand, Vancomycin and Linezolid are preferred for most of the infection with gram-positive aerobes. Continuous surveillance of resistant bacteria is required for empiric therapy.

Keywords: antibiotic resistant, antimicrobial susceptibility, diabetic foot ulcer, surveillance

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7318 Impact of Ethnoscience-Based Teaching Approach: Thinking Relevance, Effectiveness and Learner Retention in Physics Concepts of Optics

Authors: Rose C.Anamezie, Mishack T. Gumbo

Abstract:

Physics learners’ poor retention, which culminates in poor achievement due to teaching approaches that are unrelated to learners’ in non-Western cultures, warranted the study. The tenet of this study was to determine the effectiveness of the ethnoscience-based teaching (EBT) approach on learners’ retention in the Physics concept of Optics in the Awka Education zone of Anambra State- Nigeria. Two research questions and three null hypotheses tested at a 0.05 level of significance guided the study. The design adopted for the study was Quasi-experimental. Specifically, a non-equivalent control group design was adopted. The population for the study was 4,825 SS2 Physics learners in the zone. 160 SS2 learners were sampled using purposive and random sampling. The experimental group was taught rectilinear propagation of light (RPL) using the EBT approach, while the control group was taught the same topic using the lecture method. The instrument for data collection was the 50 Physics Retention Test (PRT) which was validated by three experts and tested for reliability using Kuder-Richardson’s formula-20, which yielded coefficients of 0.81. The data were analysed using mean, standard deviation and analysis of co-variance (p< .05). The results showed higher retention for the use of the EBT approach than the lecture method, while there was no significant gender-based factor in the learners’ retention in Physics. It was recommended that the EBT approach, which bridged the gender gap in Physics retention, be adopted in secondary school teaching and learning since it could transform science teaching, enhance learners’ construction of new science concepts based on their existing knowledge and bridge the gap between Western science and learners’ worldviews.

Keywords: Ethnoscience-based teaching, optics, rectilinear propagation of light, retention

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7317 Assessment of Low Income Housing Delivery, Accessibility and Affordability Problem in Nigeria

Authors: Asimiyu Mohammed Jinadu

Abstract:

Housing is a basic necessity of life. Housing plays a central role in the life of living organisms as it provides the basic platform for the life support systems in human settlements. It is considered a social service and a basic right. Despite the importance of housing, Nigeria as a nation is faced with the problem of quantitative and qualitative shortfall in the number of housing units required to accommodate the citizens. This study examined the accessibility and affordability problems of low-income housing in Nigeria. It relied on secondary data obtained for the records of government ministries and agencies. Descriptive statistics were used in the analysis, and the information was presented in simple tables and charts. The findings show that over the years the government has provided serviced plots of land, owner occupier houses and mortgage loans for the people. As at 2016, the Federal Housing Authority (FHA) has completed a total of 23,038 housing units while another 14, 488 units were on-going under the Public Private Partnership scheme across the country. The study revealed that a total of 910, 671 housing units were proposed by the Government under the various low-income housing programmes between 1960 and 2017, but only 156, 336 units were delivered within the period, representing 17.17% success rate. Amongst others, the low-income group faced the problems of low access to and unaffordability of the few low-income housing delivered in Nigeria. The study recommended that all abandoned housing projects should be reviewed, rationalized, completed and made available to the targeted low-income people. Investment in micro housing finance, design and implementation of pro-poor housing programme and massive investment in innovative slum upgrading programmes by both the government and private sector are also recommended to ameliorate the housing problems of the low-income group in Nigeria.

Keywords: housing, low income group, problem, programme

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7316 Designing a Learning Table and Game Cards for Preschoolers for Disaster Risk Reduction (DRR) on Earthquake

Authors: Mehrnoosh Mirzaei

Abstract:

Children are among the most vulnerable at the occurrence of natural disasters such as earthquakes. Most of the management and measures which are considered for both before and during an earthquake are neither suitable nor efficient for this age group and cannot be applied. On the other hand, due to their age, it is hard to educate and train children to learn and understand the concept of earthquake risk mitigation as matters like earthquake prevention and safe places during an earthquake are not easily perceived. To our knowledge, children’s awareness of such concepts via their own world with the help of games is the best training method in this case. In this article, the researcher has tried to consider the child an active element before and during the earthquake. With training, provided by adults before the incidence of an earthquake, the child has the ability to learn disaster risk reduction (DRR). The focus of this research is on learning risk reduction behavior and regarding children as an individual element. The information of this article has been gathered from library resources, observations and the drawings of 10 children aged 5 whose subject was their conceptual definition of an earthquake who were asked to illustrate their conceptual definition of an earthquake; the results of 20 questionnaires filled in by preschoolers along with information gathered by interviewing them. The design of the suitable educational game, appropriate for the needs of this age group, has been made based on the theory of design with help of the user and the priority of children’s learning needs. The final result is a package of a game which is comprised of a learning table and matching cards showing sign marks for safe and unsafe places which introduce the safe behaviors and safe locations before and during the earthquake. These educational games can be used both in group contexts in kindergartens and on an individual basis at home, and they help in earthquake risk reduction.

Keywords: disaster education, earthquake sign marks, learning table, matching card, risk reduction behavior

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7315 Perceptual and Ultrasound Articulatory Training Effects on English L2 Vowels Production by Italian Learners

Authors: I. Sonia d’Apolito, Bianca Sisinni, Mirko Grimaldi, Barbara Gili Fivela

Abstract:

The American English contrast /ɑ-ʌ/ (cop-cup) is difficult to be produced by Italian learners since they realize L2-/ɑ-ʌ/ as L1-/ɔ-a/ respectively, due to differences in phonetic-phonological systems and also in grapheme-to-phoneme conversion rules. In this paper, we try to answer the following research questions: Can a short training improve the production of English /ɑ-ʌ/ by Italian learners? Is a perceptual training better than an articulatory (ultrasound - US) training? Thus, we compare a perceptual training with an US articulatory one to observe: 1) the effects of short trainings on L2-/ɑ-ʌ/ productions; 2) if the US articulatory training improves the pronunciation better than the perceptual training. In this pilot study, 9 Salento-Italian monolingual adults participated: 3 subjects performed a 1-hour perceptual training (ES-P); 3 subjects performed a 1-hour US training (ES-US); and 3 control subjects did not receive any training (CS). Verbal instructions about the phonetic properties of L2-/ɑ-ʌ/ and L1-/ɔ-a/ and their differences (representation on F1-F2 plane) were provided during both trainings. After these instructions, the ES-P group performed an identification training based on the High Variability Phonetic Training procedure, while the ES-US group performed the articulatory training, by means of US video of tongue gestures in L2-/ɑ-ʌ/ production and dynamic view of their own tongue movements and position using a probe under their chin. The acoustic data were analyzed and the first three formants were calculated. Independent t-tests were run to compare: 1) /ɑ-ʌ/ in pre- vs. post-test respectively; /ɑ-ʌ/ in pre- and post-test vs. L1-/a-ɔ/ respectively. Results show that in the pre-test all speakers realize L2-/ɑ-ʌ/ as L1-/ɔ-a/ respectively. Contrary to CS and ES-P groups, the ES-US group in the post-test differentiates the L2 vowels from those produced in the pre-test as well as from the L1 vowels, although only one ES-US subject produces both L2 vowels accurately. The articulatory training seems more effective than the perceptual one since it favors the production of vowels in the correct direction of L2 vowels and differently from the similar L1 vowels.

Keywords: L2 vowel production, perceptual training, articulatory training, ultrasound

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7314 Artificial Intelligence Based Method in Identifying Tumour Infiltrating Lymphocytes of Triple Negative Breast Cancer

Authors: Nurkhairul Bariyah Baharun, Afzan Adam, Reena Rahayu Md Zin

Abstract:

Tumor microenvironment (TME) in breast cancer is mainly composed of cancer cells, immune cells, and stromal cells. The interaction between cancer cells and their microenvironment plays an important role in tumor development, progression, and treatment response. The TME in breast cancer includes tumor-infiltrating lymphocytes (TILs) that are implicated in killing tumor cells. TILs can be found in tumor stroma (sTILs) and within the tumor (iTILs). TILs in triple negative breast cancer (TNBC) have been demonstrated to have prognostic and potentially predictive value. The international Immune-Oncology Biomarker Working Group (TIL-WG) had developed a guideline focus on the assessment of sTILs using hematoxylin and eosin (H&E)-stained slides. According to the guideline, the pathologists use “eye balling” method on the H&E stained- slide for sTILs assessment. This method has low precision, poor interobserver reproducibility, and is time-consuming for a comprehensive evaluation, besides only counted sTILs in their assessment. The TIL-WG has therefore recommended that any algorithm for computational assessment of TILs utilizing the guidelines provided to overcome the limitations of manual assessment, thus providing highly accurate and reliable TILs detection and classification for reproducible and quantitative measurement. This study is carried out to develop a TNBC digital whole slide image (WSI) dataset from H&E-stained slides and IHC (CD4+ and CD8+) stained slides. TNBC cases were retrieved from the database of the Department of Pathology, Hospital Canselor Tuanku Muhriz (HCTM). TNBC cases diagnosed between the year 2010 and 2021 with no history of other cancer and available block tissue were included in the study (n=58). Tissue blocks were sectioned approximately 4 µm for H&E and IHC stain. The H&E staining was performed according to a well-established protocol. Indirect IHC stain was also performed on the tissue sections using protocol from Diagnostic BioSystems PolyVue™ Plus Kit, USA. The slides were stained with rabbit monoclonal, CD8 antibody (SP16) and Rabbit monoclonal, CD4 antibody (EP204). The selected and quality-checked slides were then scanned using a high-resolution whole slide scanner (Pannoramic DESK II DW- slide scanner) to digitalize the tissue image with a pixel resolution of 20x magnification. A manual TILs (sTILs and iTILs) assessment was then carried out by the appointed pathologist (2 pathologists) for manual TILs scoring from the digital WSIs following the guideline developed by TIL-WG 2014, and the result displayed as the percentage of sTILs and iTILs per mm² stromal and tumour area on the tissue. Following this, we aimed to develop an automated digital image scoring framework that incorporates key elements of manual guidelines (including both sTILs and iTILs) using manually annotated data for robust and objective quantification of TILs in TNBC. From the study, we have developed a digital dataset of TNBC H&E and IHC (CD4+ and CD8+) stained slides. We hope that an automated based scoring method can provide quantitative and interpretable TILs scoring, which correlates with the manual pathologist-derived sTILs and iTILs scoring and thus has potential prognostic implications.

Keywords: automated quantification, digital pathology, triple negative breast cancer, tumour infiltrating lymphocytes

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7313 Siderophore Receptor Protein from Klebsiella pneumoniae as a Promising Immunogen for Serotype-Independent Therapeutic Lead Development

Authors: Sweta Pandey, Samridhi Dhyani, Susmita Chaudhuri

Abstract:

Klebsiella pneumoniae causes a wide range of infections, including urinary tract infections, sepsis, bacteremia, pneumonia, and liver abscesses. The emergence of multi-drug resistance in this bacterium led to a major setback for clinical management. WHO also endorsed a need for finding alternative therapy to antibiotics for the treatment of these infections. Development of vaccines and passive antibody therapy has been proven as a potent alternative to antibiotics in the case of MDR, XDR, and PDR Klebsiella infections. Siderophore receptors have been demonstrated to be overexpressed for the internalization of iron siderophore complexes during infections in most Gram-negative bacteria. For the present study, immune response to siderophore receptors to establish this protein as a potential immunogen for the development of therapeutic leads was explored. Clinical strains of Klebsiella pneumoniae were grown in iron-deficient conditions, and the iron-regulated outer membrane proteins were extracted and characterized through mass spectrometry for specific identification. The gene for identified protein was cloned in pET- 28a vector and expressed in E. coli. The native protein and the recombinant protein were isolated and purified and used as antigens for the generation of immune response in BALB/c mice. The native protein of Klebsiella pneumoniae grown in iron-deficient conditions was identified as FepA (Ferrienterobactin receptor) and other siderophore receptors. This 80 kDa protein generated an immune response in BALB/c mice. The antiserum from mice after subsequent booster doses was collected and showed binding with FepA protein in western blot and phagocytic uptake of the K. pneumoniae in the presence antiserum from immunized mice also observed from the animal studies after bacterial challenge post immunisation in mice have shown bacterial clearance. The antiserum from mice showed binding and clearance of the Klebsiella pneumoniae bacteria in vitro and in vivo. These antigens used for generating an active immune response in mice can further be used for therapeutic monoclonal antibody development against Klebsiella pneumoniae infections.

Keywords: antiserum, FepA, Klebsiella pneumoniae, multi drug resistance, siderophore receptor

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7312 Influence of Gestational Diabetes Mellitus on the Activity of Steroid C17-Hydroxylase-C17,20-Lyase in Patients with Intrahepatic Cholestasis of Pregnancy

Authors: Leona Ondrejikova, Martin Hill, Antonin Parizek

Abstract:

The incidence of gestational diabetes mellitus (GDM) is higher in women predisposed to developing intrahepatic cholestasis of pregnancy (ICP). Both diseases are associated with altered steroidogenesis when compared with none-ICP controls. However, the effect of GDM on circulating steroids in ICP patients remains unclear. The question remains, whether the levels of circulating steroids differ between ICP patients with and without GDM. In total 10 ICP patients without GDM (ICP+GDM-), 7 ICP patients with GDM (ICP+GDM+), and 15 controls (ICP-GDM-) were monitored during late gestation, at labor, and during three periods postpartum (day 5, week 3, and week 6 postpartum) (Šimják et al., 2018). The relationships between steroid profiles and patients’ status were evaluated using the ANOVA model consisting of subject factor, between-subject factors Group (ICP+GDM+, ICP+GDM-, ICP-GDM-), gestational age at the diagnosis of ICP and gestational age at labor, and within-subject factor Stage and ICP × Stage interaction. The levels of the C21 and C19 Δ5 steroids and 5α/β-reduced C19 steroids were highest in ICP+GDM+, while those for the ICP-GDM-, and ICP+GDM- groups were lower. In the C21 Δ4 steroids and their 5α/β-reduced metabolites, the steroid levels were highest in the ICP+GDM-, intermediate in the ICP-GDM- and lowest in the ICP+GDM+ group. This higher concentration in ICP+GDM- group may be of importance as the 5α-pregnane-3α,20α-diol disulfate, is considered as the substance inducing ICP. In general, these data show that the comorbidity with GDM substantially changes the steroidome in ICP patients towards the higher activity of steroid CYP17A1 lyase step in adrenal zona reticularis reduced CYP17A1 hydroxylase step in zona fasciculata. This is consistent with our previously published hypothesis about the critical role of maternal zona reticularis in the pathophysiology of ICP. Our present data also indicate that the comorbidity with GDM might moderate the gravity of the ICP in this way.

Keywords: CYP17A1, GC-MS, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy

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7311 Developing a Web-Based Tender Evaluation System Based on Fuzzy Multi-Attributes Group Decision Making for Nigerian Public Sector Tendering

Authors: Bello Abdullahi, Yahaya M. Ibrahim, Ahmed D. Ibrahim, Kabir Bala

Abstract:

Public sector tendering has traditionally been conducted using manual paper-based processes which are known to be inefficient, less transparent and more prone to manipulations and errors. The advent of the Internet and the World Wide Web has led to the development of numerous e-Tendering systems that addressed some of the problems associated with the manual paper-based tendering system. However, most of these systems rarely support the evaluation of tenders and where they do it is mostly based on the single decision maker which is not suitable in public sector tendering, where for the sake of objectivity, transparency, and fairness, it is required that the evaluation is conducted through a tender evaluation committee. Currently, in Nigeria, the public tendering process in general and the evaluation of tenders, in particular, are largely conducted using manual paper-based processes. Automating these manual-based processes to digital-based processes can help in enhancing the proficiency of public sector tendering in Nigeria. This paper is part of a larger study to develop an electronic tendering system that supports the whole tendering lifecycle based on Nigerian procurement law. Specifically, this paper presents the design and implementation of part of the system that supports group evaluation of tenders based on a technique called fuzzy multi-attributes group decision making. The system was developed using Object-Oriented methodologies and Unified Modelling Language and hypothetically applied in the evaluation of technical and financial proposals submitted by bidders. The system was validated by professionals with extensive experiences in public sector procurement. The results of the validation showed that the system called NPS-eTender has an average rating of 74% with respect to correct and accurate modelling of the existing manual tendering domain and an average rating of 67.6% with respect to its potential to enhance the proficiency of public sector tendering in Nigeria. Thus, based on the results of the validation, the automation of the evaluation process to support tender evaluation committee is achievable and can lead to a more proficient public sector tendering system.

Keywords: e-Tendering, e-Procurement, group decision making, tender evaluation, tender evaluation committee, UML, object-oriented methodologies, system development

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7310 Possible Mechanism of DM2 Development in OSA Patients Mediated via Rev-Erb-Alpha and NPAS2 Proteins

Authors: Filip Franciszek Karuga, Szymon Turkiewicz, Marta Ditmer, Marcin Sochal, Piotr Białasiewicz, Agata Gabryelska

Abstract:

Circadian rhythm, an internal coordinator of physiological processes is composed of a set of semi-autonomous clocks. Clocks are regulated through the expression of circadian clock genes which form feedback loops, creating an oscillator. The primary loop consists of activators: CLOCK, BMAL1 and repressors: CRY, PER. CLOCK can be substituted by the Neuronal PAS Domain Protein 2 (NPAS2). Orphan nuclear receptor (REV-ERB-α) is a component of the secondary major loop, modulating the expression of BMAL1. Circadian clocks might be disrupted by the obstructive sleep apnea (OSA), which has also been associated with type II diabetes mellitus (DM2). Interestingly, studies suggest that dysregulation of NPAS2 and REV-ERB-α might contribute to the pathophysiology of DM2 as well. The goal of our study was to examine the role of NPAS2 and REV-ERB-α in DM2 in OSA patients. After examination of the clinical data, all participants underwent polysomnography (PSG) to assess their apnea-hypopnea index (AHI). Based on the acquired data participants were assigned to one of 3 groups: OSA (AHI>30, no DM2; n=17 for NPAS2 and 34 for REV-ERB-α), DM2 (AHI>30 + DM2; n=7 for NPAS2 and 15 for REV-ERB-α) and control group (AHI<5, no DM2; n=16 for NPAS2 and 31 for REV-ERB-α). ELISA immunoassay was performed to assess the serum protein level of REV-ERB-α and NPAS2. The only statistically significant difference between groups was observed in NPAS2 protein level (p=0.037). Post-hoc analysis showed significant differences between the OSA and the control group (p=0.017). AHI and NPAS2 level was significantly correlated (r=-0.478, p=0.002) in all groups. A significant correlation was observed between the REV-ERB-α level and sleep efficiency (r=0.617, p=0.005) as well as sleep maintenance efficiency (r=0.645, p=0.003) in the OSA group. We conclude, that NPAS2 is associated with OSA severity and might contribute to metabolic sequelae of this disease. REV-ERB-α on the other hand can influence sleep continuity and efficiency.

Keywords: OSA, diabetes mellitus, endocrinology, chronobiology

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7309 The Cardiac Diagnostic Prediction Applied to a Designed Holter

Authors: Leonardo Juan Ramírez López, Javier Oswaldo Rodriguez Velasquez

Abstract:

We have designed a Holter that measures the heart´s activity for over 24 hours, implemented a prediction methodology, and generate alarms as well as indicators to patients and treating physicians. Various diagnostic advances have been developed in clinical cardiology thanks to Holter implementation; however, their interpretation has largely been conditioned to clinical analysis and measurements adjusted to diverse population characteristics, thus turning it into a subjective examination. This, however, requires vast population studies to be validated that, in turn, have not achieved the ultimate goal: mortality prediction. Given this context, our Insight Research Group developed a mathematical methodology that assesses cardiac dynamics through entropy and probability, creating a numerical and geometrical attractor which allows quantifying the normalcy of chronic and acute disease as well as the evolution between such states, and our Tigum Research Group developed a holter device with 12 channels and advanced computer software. This has been shown in different contexts with 100% sensitivity and specificity results.

Keywords: attractor , cardiac, entropy, holter, mathematical , prediction

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7308 Applications of Multivariate Statistical Methods on Geochemical Data to Evaluate the Hydrocarbons Source Rocks and Oils from Ghadames Basin, NW Libya

Authors: Mohamed Hrouda

Abstract:

The Principal Component Analysis (PCA) was performed on a dataset comprising 41 biomarker concentrations from twenty-three core source rocks samples and seven oil samples from different location, with the objective of establishing the major sources of variance within the steranes, tricyclic terpanes, hopanes, and triaromatic steroid. This type of analysis can be used as an aid when deciding which molecular biomarker maturity, source facies or depositional environment parameters should be plotted, because the principal component loadings plots tend to extract the biomarker variables related to maturity, source facies or depositional environment controls. Facies characterization of the source rock samples separate the Silurian and Devonian source rock samples into three groups. Maturity evaluation of source rock samples based on biomarker and aromatic hydrocarbon distributions indicates that not all the samples are strongly affected by maturity, the Upper Devonian samples from wells located in the northern part of the basin are immature, whereas the other samples which have been selected from the Lower Silurian are mature and have reached the main stage of the oil window, the Lower Silurian source rock strata revealed a trend of increasing maturity towards the south and southwestern part of Ghadames Basin. Most of the facies-based parameters employed in this project using biomarker distributions clearly separate the oil samples into three groups. Group I contain oil samples from wells within Al-Wafa oil field Located in the south western part of the basin, Group II contains oil samples collected from Al-Hamada oil field complex in the south and the third group contains oil samples collected from oil fields located in the north

Keywords: Ghadamis basin, geochemistry, silurian, devonian

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7307 Numerical Analysis and Parametric Study of Granular Anchor Pile on Expansive Soil Using Finite Element Method: Case of Addis Ababa, Bole Sub-City

Authors: Abdurahman Anwar Shfa

Abstract:

Addis Ababa is among the fastest-growing urban areas in the country. There are many new constructions of public and private condominiums and large new low rising residential buildings for residents. But the wide range of heaving problems of expansive soil in the city become a major difficulty for the construction sector, especially in low rising buildings, by causing different problems such as distortion and cracking of floor slabs, cracks in grade beams, and walls, jammed or misaligned Doors and Windows; failure of blocks supporting grade beams. Hence an attractive and economical design solution may be required for such type of problem. Therefore, this research works to publicize a recent innovation called the Granular Anchor Pile system for the reduction of the heave effect of expansive soil. This research is written for the objective of numerical investigation of the behavior of Granular Anchor Pile under the heave using Finite element analysis PLAXIS 3D program by means of studying the effect of different parameters like length of the pile, diameter of pile, and pile group by applying prescribed displacement of 10% of pile diameter at the center of granular pile anchor. An additional objective is examining the suitability of Granular Anchor Pile as an alternative solution for heave problems in expansive soils mostly for low rising buildings found in Addis Ababa City, especially in Bole Sub-City, by considering different factors such as the local availability of construction materials, economy for the construction, installation process condition, environmental benefit, time consumption and performance of the pile. Accordingly, the performance of the pile improves when the length of the pile increases. This is due to an increase in the self-weight of the pile and friction mobilized between the pile and soil interface. Additionally, the uplift capacity of the pile decreases when increasing the pile diameter and spacing between the piles in the group due to a reduction in the number of piles in the group. But, few cases show that the uplift capacity of the pile increases with increasing the pile diameter for a constant number of piles in the group and increasing the spacing between the pile and in the case of single pile capacity. This is due to the increment of piles' self-weight and surface area of the pile group and also the decrement of stress overlap in the soil caused by piles respectively. According to the suitability analysis, it is observed that Granular Anchor Pile is sensible or practical to apply for the actual problem of Expansive soil in a low rising building constructed in the country because of its convenience for all considerations.

Keywords: expansive soil, granular anchor pile, PLAXIS, suitability analysis

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7306 Comparison of Transforming Growth Factor-β1 Levels in the Human Gingival Sulcus during Canine Retraction Using Elastic Chain and Closed Coil Spring

Authors: Sri Suparwitri

Abstract:

When an orthodontic force is applied to a tooth, an inflammatory response is initiated then lead to bone remodeling process, and the process accommodates tooth movement. One of cytokine that plays a prominent role in bone remodeling process was transforming growth factor-beta 1 (TGF-β1). The purpose of this study was to identify and compare changes of TGF-β1 in human gingival crevicular fluid during canine retraction using elastic chain and closed coil spring. Ten patients (mean age 20.7 ± 2.9 years) participated. The patients were entering the space closure phase of fixed orthodontic treatment. An upper canine of each patient was retracted using elastic chain, and the contralateral canine was retracted using closed coil spring. Gingival crevicular fluid samples were collected from the canine teeth before and 7 days after the force was applied. Transforming growth factor-beta 1 was determined by enzyme-linked immunosorbent assay (ELISA). The concentrations of TGF-β1 at 7 days were significantly higher compared to before canine retraction in both groups. In the evaluation of between-group difference, before retraction, the difference was insignificant, whereas at 7 days significantly higher values were determined in the closed coil spring group compared to elastic chain group. The result suggests that TGF-β1 is associated with the bone remodeling that occurs during canine distalization movement. Closed coil spring gave higher TGF-β1 concentrations thus more bone remodeling occurred and may be considered the treatment of choice.

Keywords: closed coil spring, elastic chain, gingival crevicular fluid, TGF-β1

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7305 CT Doses Pre and Post SAFIRE: Sinogram Affirmed Iterative Reconstruction

Authors: N. Noroozian, M. Halim, B. Holloway

Abstract:

Computed Tomography (CT) has become the largest source of radiation exposure in modern countries however, recent technological advances have created new methods to reduce dose without negatively affecting image quality. SAFIRE has emerged as a new software package which utilizes full raw data projections for iterative reconstruction, thereby allowing for lower CT dose to be used. this audit was performed to compare CT doses in certain examinations before and after the introduction of SAFIRE at our Radiology department which showed CT doses were significantly lower using SAFIRE compared with pre-SAFIRE software at SAFIRE 3 setting for the following studies:CSKUH Unenhanced brain scans (-20.9%), CABPEC Abdomen and pelvis with contrast (-21.5%), CCHAPC Chest with contrast (-24.4%), CCHAPC Abdomen and pelvis with contrast (-16.1%), CCHAPC Total chest, abdomen and pelvis (-18.7%).

Keywords: dose reduction, iterative reconstruction, low dose CT techniques, SAFIRE

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7304 Evaluation of Genetic Resistance to Haemonchus Contortus in Teddy and Beetal Goat Breeds of Punjab, Pakistan

Authors: Muhammad S. Sajid, Asim Shamim, Muhammad Nisar Khan, Ashfaq A. Chatta, Muhammad Saqib

Abstract:

Goats (Capra hircus) are a valued asset for resource poor farmers globally. But the parasitic infection especially Haemonchus contortus (Trichostrongylid), impact the health and production of goats globally. The present study intended to evaluate resilient and resistance to Haemonchus contortus in indigenous goat breeds (Teddy and Beetal) of Punjab, Pakistan. Out of 60, 30 goats of each breed were divided into 6 groups and each group contain five goats. Two group of each breed received challenged infection with 12000 and 18000 L3 (third stage) larvae of Haemonchus contortus under two infection protocol that is early and trickle and remaining two group of each breed was kept as control. Resilient and resistance of each breed was then measured on the basis of their phenotypic markers like: faecal egg counts, packed cell volume, FAMACHA score system, body weight, total protein, albumin and worm count on 2nd, 4th, 6th, and 8th week of post infection. Variation in response of each goat breeds to Haemonchus contortus was observed. Teddy breed showed significant (P < 0.05)resistance as compared to Beetal. It is probably first attempt to report an evaluation of goat breed response towards Haemonchus contortus in Pakistan. It was concluded that Teddy goats have a greater genetic tendency to resist against to the Haemonchus contortus infection and this breed could be kept and bred from the economic point of view. Evaluation of genetic markers are like: gene, protein expression, Immunoglobulin, Histamines and interleukins determination are recommended for future studies which can be helpful to be fined resistant breed of goats.

Keywords: goat, beetal, teddy, haemonchus contortus, resistance, resilience, phenotypic markers

Procedia PDF Downloads 352
7303 Modeling a Feedback Concept in a Spherical Thundercloud Cell

Authors: Zemlianskaya Daria, Egor Stadnichuk, Ekaterina Svechnikova

Abstract:

Relativistic runaway electron avalanches (RREAs) are generally accepted as a source of thunderstorms gamma-ray radiation. Avalanches' dynamics in the electric fields can lead to their multiplication via gamma-rays and positrons, which is called relativistic feedback. This report shows that a non-uniform electric field geometry leads to the new RREAs multiplication mechanism - “geometric feedback”, which occurs due to the exchange of high-energy particles between different accelerating regions within a thundercloud. This report will present the results of the simulation in GEANT4 of feedback in a spherical cell. Necessary conditions for the occurrence of geometric feedback were obtained from it.

Keywords: electric field, GEANT4, gamma-rays, relativistic runaway electron avalanches (RREAs), relativistic feedback, the thundercloud

Procedia PDF Downloads 161
7302 Kinetic Modeling of Transesterification of Triacetin Using Synthesized Ion Exchange Resin (SIERs)

Authors: Hafizuddin W. Yussof, Syamsutajri S. Bahri, Adam P. Harvey

Abstract:

Strong anion exchange resins with QN+OH-, have the potential to be developed and employed as heterogeneous catalyst for transesterification, as they are chemically stable to leaching of the functional group. Nine different SIERs (SIER1-9) with QN+OH- were prepared by suspension polymerization of vinylbenzyl chloride-divinylbenzene (VBC-DVB) copolymers in the presence of n-heptane (pore-forming agent). The amine group was successfully grafted into the polymeric resin beads through functionalization with trimethylamine. These SIERs are then used as a catalyst for the transesterification of triacetin with methanol. A set of differential equations that represents the Langmuir-Hinshelwood-Hougen-Watson (LHHW) and Eley-Rideal (ER) models for the transesterification reaction were developed. These kinetic models of LHHW and ER were fitted to the experimental data. Overall, the synthesized ion exchange resin-catalyzed reaction were well-described by the Eley-Rideal model compared to LHHW models, with sum of square error (SSE) of 0.742 and 0.996, respectively.

Keywords: anion exchange resin, Eley-Rideal, Langmuir-Hinshelwood-Hougen-Watson, transesterification

Procedia PDF Downloads 350
7301 The Influence of Migration on Migrants' Culture: A Study on Egyptian Nubians' Migration to Investigate Culture Changes

Authors: Tarek Hassan, Sanaa Abouras

Abstract:

Some factors such as interaction of migration process, cultural identity have an impact in a way that may lead to cultural disinheritance. Even if migrants' culture would not be lost, it may be affected by the new society culture. Therefore, it is anticipated that migration of an ethnic group would impact the culture of that group. Nubians; an ethnic group originated in South Egypt, have experienced migration that took place in the sixties of the past century. Nubians were forced to leave their origin land and relocate to Kom Ombo; an Egyptian town to the north of Aswan. The effect of migration on national culture, social homogeneity or the interest of social contact influences the attitudes of natives towards migration. Hence, it is very important for societies to help migrants to adapt to the new culture and at the same time not to impede migrants' effort to maintain their own culture. This study aims to investigate the effect of internal migration on the culture of Egyptian Nubians in order to predict if Nubian can maintain their own culture after the migration. Research question: what is the cultural influence of Nubians' migration from Egyptian Nubia to their new destinations? The researchers' hypothesis: there is mutual influence between the two cultures of Nubians and non-Nubians in Egypt. Results supported researchers' hypothesis as they observed that the Nubians managed to reserve balance between the maintenance of their own culture and the adoption of some cultural features of the community of their new destination(s). Also, the study examined why Nubians adhere to their culture although they left their land forever. Questionnaire and interviews were used to collect data from 80 informants; 40 Nubians and 40 non-Nubians in Kom-Ombo and the two cities of Cairo and Alexandria. Results suggested that there is obvious mutual cultural impact between Nubians and non-Nubians. The findings of this study would trigger the researchers to conduct further research on minorities for the deeper understanding of the impact of/on the culture of minorities.

Keywords: culture change, culture influence, culture maintenance, minority migration

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7300 Efficacy of Learning: Digital Sources versus Print

Authors: Rahimah Akbar, Abdullah Al-Hashemi, Hanan Taqi, Taiba Sadeq

Abstract:

As technology continues to develop, teaching curriculums in both schools and universities have begun adopting a more computer/digital based approach to the transmission of knowledge and information, as opposed to the more old-fashioned use of textbooks. This gives rise to the question: Are there any differences in learning from a digital source over learning from a printed source, as in from a textbook? More specifically, which medium of information results in better long-term retention? A review of the confounding factors implicated in understanding the relationship between learning from the two different mediums was done. Alongside this, a 4-week cohort study involving 76 1st year English Language female students was performed, whereby the participants were divided into 2 groups. Group A studied material from a paper source (referred to as the Print Medium), and Group B studied material from a digital source (Digital Medium). The dependent variables were grading of memory recall indexed by a 4 point grading system, and total frequency of item repetition. The study was facilitated by advanced computer software called Super Memo. Results showed that, contrary to prevailing evidence, the Digital Medium group showed no statistically significant differences in terms of the shift from Remember (Episodic) to Know (Semantic) when all confounding factors were accounted for. The shift from Random Guess and Familiar to Remember occurred faster in the Digital Medium than it did in the Print Medium.

Keywords: digital medium, print medium, long-term memory recall, episodic memory, semantic memory, super memo, forgetting index, frequency of repetitions, total time spent

Procedia PDF Downloads 278
7299 Effects of in Ovo Injection of Royal Jelly on Hatchability, One-Day Old Chickens Quality, Total Antioxidant Status and Blood Lipoproteins

Authors: Amin Adeli, Maryam Zarei

Abstract:

Background and purpose: Royal jelly (RJ) is a natural product with anti-hyperlipidemic and antioxidant properties. In ovo administration of RJ may improve lipid profile and antioxidant properties. This study was conducted to evaluate, for first time, the effects of in ovo injection of the RJ on hatchability, one-day old chick quality, total antioxidant status and blood lipoproteins. Methods: 400 incubating eggs produced by Ross 308 strain (52 weeks of age in first stage of production) were prepared and assigned into 4 groups (n=100) and 4 replications per group (n=25). These 4 groups were injected by the following pattern: 1) 0.1 ml normal saline (control), 2) 0.1 mg RJ+0.1 ml normal saline, 3) 0.2 mg RJ+0.1 ml normal saline, and 4) 0.3 mg RJ+0.1 ml normal saline. Injections were performed using a laminar flow system Lipid profile, antioxidant properties, hatchability, and one-day old chicken quality were assessed. Results: The administration of RJ at concentration of 0.1increased the percentage of hatchability compared to concentration of 0.2 and control, significant differences have not been observed among groups for quality scores (P>0.05). The results showed that in ovo injection of the RJ did not have any significant effects on lipid profile; but administration of the RJ only decreased High-density lipoprotein (HDL cholesterol, HDL-C) (P<0.05). The results showed that injection of the RJ at concentration of 0.3 increased total antioxidant capacity (TAC) compared to control group (p<0.05). Injection of the RJ progressively increased gluthation peroxidase (GPx) activity (p<0.05). The results showed that injection of the RJ decreased superoxide dismutase (SOD) compared to control group (p<0.05). Conclusion: In ovo injection of the RJ at the highest concentration increased TAC and GPx, but it did not have significant effects on lipid profile. Future studies are needed to investigate the effects of the RJ on the above-mentioned mechanisms.

Keywords: antioxidant enzymes, chicken quality, hatchability, royal jelly

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7298 Effect of Age and Physiological Status on Some Serum Energy Metabolites and Progesterone in Ouled Djellal Breed Ewes in Algeria

Authors: B. Safsaf, M. Tlidjane, B. Mamache, M. A. Dehimi, H. Boukrous, Aly A. Hassan

Abstract:

The aim of this study is to determine the effect of age and physiological status on progesterone and energy metabolism of Ouled Djellal (O.D) breed ewes. 40 healthy ewes were divided into two groups, primiparous and multiparous, with 20 ewes in each group. The body weights (BW) (kg) were 46.6 ± 4.20 and 59.2 ± 3.02, and consuming less 25 to 30% of their basal energetic requirements. The values of serum glucose, triglycerides and cholesterol were lower in pregnant than in non-pregnant ewes. The high to very high significant differences were found during the 15th week of pregnancy for glycaemia and triglyceridemia respectively. Concerning serum progesterone, a very highly significant difference (p < 0.001) was noted in the pregnant group, and the values were higher in MP than in PP. After lambing, the triglyceridemia values were slightly lower in primiparous than in multiparous pregnant ewes. In order to prevent imbalance during critical periods of reproduction, we can use the serum metabolic profile.

Keywords: age, energy metabolites, ouled djellal breed ewes, physiologic status, progesterone

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7297 Applications of AFM in 4D to Optimize the Design of Genetic Nanoparticles

Authors: Hosam Abdelhady

Abstract:

Filming the behaviors of individual DNA molecules in their environment when they interact with individual medicinal nano-polymers in a molecular scale has opened the door to understand the effect of the molecular shape, size, and incubation time with nanocarriers on optimizing the design of robust genetic Nano molecules able to resist the enzymatic degradation, enter the cell, reach to the nucleus and kill individual cancer cells in their environment. To this end, we will show how we applied the 4D AFM as a guide to finetune the design of genetic nanoparticles and to film the effects of these nanoparticles on the nanomechanical and morphological profiles of individual cancer cells.

Keywords: AFM, dendrimers, nanoparticles, DNA, gene therapy, imaging

Procedia PDF Downloads 67
7296 Use of Proton Pump Inhibitors Medications during the First Years of Life and Late Complications

Authors: Kamelia Hamza

Abstract:

Background: Proton pump inhibitors (PPIs) are the most prescribed drug classes for pediatric gastroesophageal reflux disease (GERD).Many patients are treated with these drugs for atypical manifestations attributed to gastroesophageal reflux (GER), even in the absence of proved causal relationship. There is an impression of increase use of PPI's treatment for reflux in "clalit health services," the largest health organization in Israel. In the recent years, the medicine is given without restriction, it's not limited to pediatric gastroenterologists only, but pediatricians and family doctors. The objective of this study is to evaluate the hypothesis that exposure to PPIs during the first year of life is associated with an increased risk of developing late adverse diseases: pneumonia, asthma, AGE, IBD, celiac disease, allergic disorders, obesity, attention deficit hyperactivity disorders (ADHD), autism spectrum disorders (ASD). Methods: The study is a retrospective case-control cohort study based on a computerized database of Clalit Health Services (CHS). It includes 9844 children born between 2002-2018 and reported to complain of at least one of the symptoms (reflux/ spitting up, irritability, feeding difficulties, colics). The study population included the study group (n=4922) of children exposed to PPIs at any time prior to the first year of life and a control group (n=4922) child not exposed to PPIs who were matched to each case of the study group on age, race, socioeconomic status, and year of birth. The prevalence of late complications/diseases in the study group was compared with the prevalence of late complications/diseases diagnosis between 2002-2020 in the control group. Odds ratios and 95% confidence intervals were calculated by using logistic regression models. Results: We found that compared to the control group, children exposed to PPIs in the first year of life had an increased risk of developing several late complications/ disorders: pneumonia, asthma, various allergies (urticaria, allergic rhinitis, or allergic conjunctivitis) OR, inhalant allergies, and food allergies. In addition, they showed an increased risk of being diagnosed with ADHD or ASD, but children exposed to PPIs in the first year of life had decrease the risk of obesity by 17% (OR 0.825, 95%CI 0.697-0.976). Conclusions: We found significant associations between the use of PPIs during the first year of life and subsequent development of late complications/diseases such as respiratory diseases, allergy diseases, ADHD, and ASD. More studies are needed to prove causality and determine the mechanism behind the effect of PPIs and the development of late complications.

Keywords: acid suppressing medications, proton pump inhibitors, histamine 2 blocker, late complications, gastroesophageal reflux, gastroesophageal reflux disease, acute gastroenteritis, community acquired pneumonia, asthma, allergic diseases, obesity, inflammatory bowel diseases, ulcerative colitis, crohn disease, attention deficit hyperactivity disorders, autism spectrum disorders

Procedia PDF Downloads 87
7295 Features of Normative and Pathological Realizations of Sibilant Sounds for Computer-Aided Pronunciation Evaluation in Children

Authors: Zuzanna Miodonska, Michal Krecichwost, Pawel Badura

Abstract:

Sigmatism (lisping) is a speech disorder in which sibilant consonants are mispronounced. The diagnosis of this phenomenon is usually based on the auditory assessment. However, the progress in speech analysis techniques creates a possibility of developing computer-aided sigmatism diagnosis tools. The aim of the study is to statistically verify whether specific acoustic features of sibilant sounds may be related to pronunciation correctness. Such knowledge can be of great importance while implementing classifiers and designing novel tools for automatic sibilants pronunciation evaluation. The study covers analysis of various speech signal measures, including features proposed in the literature for the description of normative sibilants realization. Amplitudes and frequencies of three fricative formants (FF) are extracted based on local spectral maxima of the friction noise. Skewness, kurtosis, four normalized spectral moments (SM) and 13 mel-frequency cepstral coefficients (MFCC) with their 1st and 2nd derivatives (13 Delta and 13 Delta-Delta MFCC) are included in the analysis as well. The resulting feature vector contains 51 measures. The experiments are performed on the speech corpus containing words with selected sibilant sounds (/ʃ, ʒ/) pronounced by 60 preschool children with proper pronunciation or with natural pathologies. In total, 224 /ʃ/ segments and 191 /ʒ/ segments are employed in the study. The Mann-Whitney U test is employed for the analysis of stigmatism and normative pronunciation. Statistically, significant differences are obtained in most of the proposed features in children divided into these two groups at p < 0.05. All spectral moments and fricative formants appear to be distinctive between pathology and proper pronunciation. These metrics describe the friction noise characteristic for sibilants, which makes them particularly promising for the use in sibilants evaluation tools. Correspondences found between phoneme feature values and an expert evaluation of the pronunciation correctness encourage to involve speech analysis tools in diagnosis and therapy of sigmatism. Proposed feature extraction methods could be used in a computer-assisted stigmatism diagnosis or therapy systems.

Keywords: computer-aided pronunciation evaluation, sigmatism diagnosis, speech signal analysis, statistical verification

Procedia PDF Downloads 290
7294 Application of MRI in Radioembolization Imaging and Dosimetry

Authors: Salehi Zahabi Saleh, Rajabi Hosaien, Rasaneh Samira

Abstract:

Yttrium-90 (90Y) radioembolisation(RE) is increasingly used for the treatment of patients with unresectable primary or metastatic liver tumours. Image-based approaches to assess microsphere distribution after RE have gained interest but are mostly hampered by the limited imaging possibilities of the Isotope 90Y. Quantitative 90Y-SPECT imaging has limited spatial resolution because it is based on 90Y Bremsstrahlung whereas 90Y-PET has better spatial resolution but low sensitivity. As a consequence, new alternative methods of visualizing the microspheres have been investigated, such as MR imaging of iron-labelled microspheres. It was also shown that MRI combines high sensitivity with high spatial and temporal resolution and with superior soft tissue contrast and thus can be used to cover a broad range of clinically interesting imaging parameters.The aim of the study in this article was to investigate the capability of MRI to measure the intrahepatic microsphere distribution in order to quantify the absorbed radiation dose in RE.

Keywords: radioembolisation, MRI, imaging, dosimetry

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7293 Effects of Unfamiliar Orthography on the Lexical Encoding of Novel Phonological Features

Authors: Asmaa Shehata

Abstract:

Prior research indicates that second language (L2) learners encounter difficulty in the distinguishing novel L2 contrasting sounds that are not contrastive in their native languages. L2 orthographic information, however, is found to play a positive role in the acquisition of non-native phoneme contrasts. While most studies have mainly involved a familiar written script (i.e., the Roman script), the influence of a foreign, unfamiliar script is still unknown. Therefore, the present study asks: Does unfamiliar L2 script play a role in creating distinct phonological representations of novel contrasting phonemes? It is predicted that subjects’ performance in the unfamiliar orthography group will outperform their counterparts’ performance in the control group. Thus, training that entails orthographic inputs can yield a significant improvement in L2 adult learners’ identification and lexical encoding of novel L2 consonant contrasts. Results are discussed in terms of their implications for the type of input introduced to L2 learners to improve their language learning.

Keywords: Arabic, consonant contrasts, foreign script, lexical encoding, orthography, word learning

Procedia PDF Downloads 246
7292 A Biophysical Model of CRISPR/Cas9 on- and off-Target Binding for Rational Design of Guide RNAs

Authors: Iman Farasat, Howard M. Salis

Abstract:

The CRISPR/Cas9 system has revolutionized genome engineering by enabling site-directed and high-throughput genome editing, genome insertion, and gene knockdowns in several species, including bacteria, yeast, flies, worms, and human cell lines. This technology has the potential to enable human gene therapy to treat genetic diseases and cancer at the molecular level; however, the current CRISPR/Cas9 system suffers from seemingly sporadic off-target genome mutagenesis that prevents its use in gene therapy. A comprehensive mechanistic model that explains how the CRISPR/Cas9 functions would enable the rational design of the guide-RNAs responsible for target site selection while minimizing unexpected genome mutagenesis. Here, we present the first quantitative model of the CRISPR/Cas9 genome mutagenesis system that predicts how guide-RNA sequences (crRNAs) control target site selection and cleavage activity. We used statistical thermodynamics and law of mass action to develop a five-step biophysical model of cas9 cleavage, and examined it in vivo and in vitro. To predict a crRNA's binding specificities and cleavage rates, we then compiled a nearest neighbor (NN) energy model that accounts for all possible base pairings and mismatches between the crRNA and the possible genomic DNA sites. These calculations correctly predicted crRNA specificity across 5518 sites. Our analysis reveals that cas9 activity and specificity are anti-correlated, and, the trade-off between them is the determining factor in performing an RNA-mediated cleavage with minimal off-targets. To find an optimal solution, we first created a scheme of safe-design criteria for Cas9 target selection by systematic analysis of available high throughput measurements. We then used our biophysical model to determine the optimal Cas9 expression levels and timing that maximizes on-target cleavage and minimizes off-target activity. We successfully applied this approach in bacterial and mammalian cell lines to reduce off-target activity to near background mutagenesis level while maintaining high on-target cleavage rate.

Keywords: biophysical model, CRISPR, Cas9, genome editing

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7291 Resistance of Mycobacterium tuberculosis to Daptomycin

Authors: Ji-Chan Jang

Abstract:

Tuberculosis is still major health problem because there is an increase of multidrug-resistant and extensively drug-resistant forms of the disease. Therefore, the most urgent clinical need is to discover potent agents and develop novel drug combination capable of reducing the duration of MDR and XDR tuberculosis therapy. Three reference strains H37Rv, CDC1551, W-Beijing GC1237 and six clinical isolates of MDRTB were tested to daptomycin in the range of 0.013 to 256 mg/L. Daptomycin is resistant to all tested M. tuberculosis strains not only laboratory strains but also clinical MDR strains that were isolated at different source. Daptomycin will not be an antibiotic of choice for treating infection of Gram positive atypical slowly growing M. tuberculosis.

Keywords: tuberculosis, daptomycin, resistance, Mycobacterium tuberculosis

Procedia PDF Downloads 364