Search results for: correlated random damping

Authors: Cheng-Chen Hsu

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Background: The ratio of the length of the second finger (index finger, 2D) to the fourth finger (ring finger, 4D) (2D:4D) is a putative marker of prenatal hormones. A low 2D:4D ratio is related to high prenatal testosterone (PT) levels. Physiological research has suggested that a low 2D:4D ratio is correlated with high sports ability. Aim: To examine the association between cardiorespiratory fitness and 2D:4D. Methods: Assessment of 2D:4D; Images of hands were collected from participants using a computer scanner. Hands were placed lightly on the surface of the plate. Image analysis was performed using Image-Pro Plus 5.0 software. Feature points were marked at the tip of the finger and at the center of the proximal crease on the second and fourth digits. Actual measurement was carried out automatically, 2D:4D was calculated by dividing 2nd by 4th digit length. YMCA 3-min Step Test; The test involves stepping up and down at a rate of 24 steps/min for 3 min; a tape recording of the correct cadence (96 beats/min) is played to assist the participant in keeping the correct pace. Following the step test, the participant immediately sits down and, within 5 s, the tester starts counting the pulse for 1 min. The score for the test, the total 1-min postexercise heart rate, reflects the heart’s ability to recover quickly. Statistical Analysis ; Pearson’s correlation (r) was used for assessing the relationship between age, physical measurements, one-minute heart rate after YMCA 3-minute step test (HR) and 2D:4D. An independent-sample t-test was used for determining possible differences in HR between subjects with low and high values of 2D:4D. All statistical analyses were carried out with SPSS 18 for Window. All P-values were two-tailed at P = 0.05, if not reported otherwise. Results: A median split by 2D:4D was applied, resulting in a high and a low group. One-minute heart rate after YMCA 3-minute step test was significantly difference between groups of male right-hand 2D:4D (p = 0.024). However, no difference in left-hand 2D:4D values between groups in male, and no digit ratio difference between groups in female. Conclusion: The results showed that cardiopulmonary fitness is related to right 2D:4D, only in men. We argue that prenatal testosterone may have an effect on cardiorespiratory fitness in male but not in female.

Keywords: college students, digit ratio, finger, step test, fitness

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Authors: Mohd Najib Mansor, Nur Syamilah Md. Noor, Abdul Rahim Anuar, Shazida Jan Mohd Khan, Ahmad Zubir Ibrahim, Badariah Hj Din, Abu Sufian Abu Bakar, Kalsom Kayat, Wan Nurmahfuzah Jannah Wan Mansor

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This study aimed and focused on the behavior of youth entrepreneurs’ especially entrepreneurial self-efficacy and the performance in micro SMEs in Malaysia. Entrepreneurship development calls for support from various quarters, and mostly the need exists to initiate a youth entrepreneurship culture and drive amongst the youth in the society. Although backed up by the government and non-government organizations, micro-entrepreneurs are still facing challenges which greatly delay their progress, growth and consequently their input towards economic advancement. Micro-entrepreneurs are confronted with unique difficulties such as uncertainty, innovation, and evolution. Reviews on the development of entrepreneurial characteristics such as need for achievement, internal locus of control, risk-taking and innovation and have been recognized as highly associated with entrepreneurial behavior. The data in this study was obtained from the Department of Statistics, Malaysia. A random sampling of 830 respondents was distributed to 14 states that involve of micro-entrepreneurs. The study adopted a quantitative approach whereby a set of questionnaire was used to gather data. Multiple regression analysis was chosen as a method of analysis testing. The result of this study is expected to provide insight into the factor affecting entrepreneurial behavior and performance of youth entrepreneurs in micro SMEs. The finding showed that the Malaysian youth entrepreneurs do not have the entrepreneurial self-efficacy within themselves in order to accomplish greater success in their business venture. The establishment of entrepreneurial schools to allow our youth to be exposed to entrepreneurship from an early age and the development of special training focuses on the creation of business network so that the continuous entrepreneurial culture is crafted.

Keywords: youth entrepreneurs, micro entrepreneurs, entrepreneurial self-efficacy, entrepreneurial performance

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Authors: Merih Welay Welesilassie

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Understanding educators' readiness to incorporate AI tools into their teaching methods requires comprehensively examining the influencing factors. This understanding is crucial, given the potential of these technologies to personalise learning experiences, improve instructional effectiveness, and foster innovative pedagogical approaches. This study evaluated factors affecting teachers' adoption of AI tools in their English language instruction by extending the Technology Acceptance Model (TAM) to encompass digital readiness support, perceived risk, and trust. A cross-sectional quantitative survey was conducted with 128 English language teachers, supplemented by qualitative data collection from 15 English teachers. The structural mode analysis indicated that implementing AI tools in Ethiopian higher education was notably influenced by digital readiness support, perceived ease of use, perceived usefulness, perceived risk, and trust. Digital readiness support positively impacted perceived ease of use, usefulness, and trust while reducing safety and privacy risks. Perceived ease of use positively correlated with perceived usefulness but negatively influenced trust. Furthermore, perceived usefulness strengthened trust in AI tools, while perceived safety and privacy risks significantly undermined trust. Trust was crucial in increasing educators' willingness to adopt AI technologies. The qualitative analysis revealed that the teachers exhibited strong content and pedagogical knowledge but needed more technology-related knowledge. Moreover, It was found that the teachers did not utilise digital tools to teach English. The study identified several obstacles to incorporating digital tools into English lessons, such as insufficient digital infrastructure, a shortage of educational resources, inadequate professional development opportunities, and challenging policies and governance. The findings provide valuable guidance for educators, inform policymakers about creating supportive digital environments, and offer a foundation for further investigation into technology adoption in educational settings in Ethiopia and similar contexts.

Keywords: digital readiness support, AI acceptance, risk, trust

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Authors: Aisha Liaquat Ali, Ghulam Sarwar Gachal, Muhammad Yusuf Sheikh

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The Parrot rose ringed (Psittaculla krameri) commonly known as Tota, belongs to the order ‘Psittaciformes’ and family ‘Psittacidea’. Its sub-species inhabiting Pakistan are Psittaculla borealis. The parrot rose-ringed has been categorized the least concern species, the core aim of the present study is to investigate the ecology and taxonomy of parrot (rose-ringed). Sampling was obtained for the taxonomic identification from various adjoining areas in City Mirpurkhas by non-random method, which was conducted from Feb to June 2017. The different parameters measured with the help of a vernier caliper, foot scale, digital weighing machine. Body parameters were measured via; length of body, length of the wings, length of tail, mass in grams. During present study, a total number of 36 specimens were collected from different localities of City Mirpurkhas (38.2%) were male and (62.7%) were female. Maximum population density of Psittaculla Krameri borealis (52.9%) was collected from Sindh Horticulture Research Station (fruit farm) Mirpurkhas. Minimum no: of Psittaculla krameri borealis (5.5%) collected in urban parks. It was observed that Psittaculla krameri borealis were in dense population during the months of ‘May’ and ‘June’ when the temperature ranged between 20°C and 45°C. A Psittaculla krameri borealis female was found the heaviest in body weight. The species of parrot (rose ringed) captured during study having green plumage, coverts were gray, upper beak, red and lower beak black, shorter tail in female long tail in the male which was similar to the Psittaculla krameri borealis.

Keywords: Mirpurkhas Sindh Pakistan, environmental ecology, parrot, rose-ringed, taxonomy

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Authors: Ammaarah Gamieldien

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Depression is a very common and serious mental illness that has a significant impact on both the social and economic aspects of sufferers worldwide. This study aimed to investigate the association between body mass index (BMI), blood pressure, and lipid profiles with mental health symptoms in university students. Secondary objectives included the associations between the variables (BMI, blood pressure, and lipids) with themselves, as they are key factors in cardiometabolic disease. Sixty-three (63) students participated in the study. Thirty-two (32) were assigned to the control group (minimal-mild depressive symptoms), while 31 were assigned to the depressive group (moderate to severe depressive symptoms). Montgomery-Asberg Depression Rating Scale (MADRS) and Beck Depression Inventory (BDI) were used to assess depressive scores. Anthropometric measurements such as weight (kg), height (m), waist circumference (WC), and hip circumference were measured. Body mass index (BMI) and ratios such as waist-to-hip ratio (WHR) and waist-to-height ratio (WtHR) were also calculated. Blood pressure was measured using an automated AfriMedics blood pressure machine, while lipids were measured using a CardioChek plus analyzer machine. Statistics were analyzed via the SPSS statistics program. There were no significant associations between anthropometric measurements and depressive scores (p > 0.05). There were no significant correlations between lipid profiles and depression when running a Spearman’s rho correlation (P > 0.05). However, total cholesterol and LDL-C were negatively associated with depression, and triglycerides were positively associated with depression after running a point-biserial correlation (P < 0.05). Overall, there were no significant associations between blood pressure measurements and depression (P > 0.05). However, there was a significant moderate positive correlation between systolic blood pressure and MADRS scores in males (P < 0.05). Depressive scores positively and strongly correlated to how long it takes participants to fall asleep. There were also significant associations with regard to the secondary objectives. This study indicates the importance of determining the prevalence of depression among university students in South Africa. If the prevalence and factors associated with depression are addressed, depressive symptoms in university students may be improved.

Keywords: depression, blood pressure, body mass index, lipid profiles, mental health symptoms

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Authors: Mohammadreza Khanmohammadi, Noureddin Nakhostin Ansari, Soofia Naghdi

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Purpose: Our study aimed to validate single item presenteeism question (SIPQ) into the Persian language for patients with low back pain. Background information: low back pain is a common health problem, and it is one of the most prevalent disorder in working people. There are the different subjective way to evaluate the effect of back pain on work productivity that one of them is by implementing single item presenteeism question. This question has not been validated into the Persian language. Method: Patients were asked to answer SIPQ and pain from 0 to 10 according to numerical rating scale (NRS). The functional rating index was administrated to evaluate construct validity. For test-retest reliability, almost 50 patients re-completed the Persian SIPQ. The construct validity of SIPQ was assessed by analyzing Spearman rank correlation between this question and the Persian version of Functional rating index questionnaire. To analyze test-retest reliability, we assessed intraclass correlation coefficient (agreement) (ICC agreement) (two-way random effects model, single measure). Results: The SIPQ score of two groups of patients (84 males, 16 females, mean age ±SD: 33.85±11.16 years, range: 19-67 years) and healthy subjects (48 male, 2 female ones, mean age ±SD: 24.24 ±8.07 years) was statistically significant. (Mann-Whitney U =198.00, P<.001). The Spearman correlation of data showed that there is a significant correlation between Persian SIPQ score and Persian FRI band (r= .559, P<.001). The ICC was .62. So, the analysis indicated good, test-retest reliability. Conclusion: This study showed that Persian version of SIPQ is reliable and valid when applied to back pain patients.

Keywords: cross cultural adaptation, economic burden, low back pain, Persian language, translation

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Authors: Mehran Nasiri, Ardeshir Poornemat

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The aim of this study was to investigate the current and ideal situations of the process of talent identification in Iranian football from the point of view of Iranian instructors of the Asian Football Confederation (AFC). This research was a descriptive-analytical study; in data collection phase a questionnaire was used, whose face validity was confirmed by experts of Physical Education and Sports Science. The reliability of questionnaire was estimated through the use of Cronbach's alpha method (0.91). This study involved 122 participants of Iranian instructors of the AFC who were selected based on stratified random sampling method. Descriptive statistics were used to describe the variables and inferential statistics (Chi-square) were used to test the hypotheses of the study at significant level (p ≤ 0.05). The results of Chi-square test related to the point of view of Iranian instructors of the AFC showed that the grass-roots scientific method was the best way to identify football players (0.001), less than 10 years old were the best ages for talent identification (0.001), the Football Federation was revealed to be the most important organization in talent identification (0.002), clubs were shown to be the most important institution in developing talents (0.001), trained scouts of Football Federation were demonstrated to be the best and most appropriate group for talent identification (0.001), and being referred by the football academy coaches was shown to be the best way to attract talented football players in Iran (0.001). It was also found that there was a huge difference between the current and ideal situation of the process of talent identification in Iranian football from the point of view of Iranian instructors of the AFC. Hence, it is recommended that the policy makers of talent identification for Iranian football provide a comprehensive, clear and systematic model of talent identification and development processes for the clubs and football teams, so that the talent identification process helps to nurture football talents more efficiently.

Keywords: current situation, talent finding, ideal situation, instructors (AFC)

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Authors: Felix Oromena Egara, Moeketsi Mosia

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The study aimed to evaluate the impact of blended learning on mathematics retention among secondary school students. Conducted in the Isoko North Local Government Area of Delta State, Nigeria, the research involved 1,235 senior class one (SS 1) students. Employing a non-equivalent control group pre-test-post-test quasi-experimental design, a sample of 70 students was selected from two secondary schools with ICT facilities through purposive sampling. Random allocation of students into experimental and control groups was achieved through balloting within each selected school. The investigation included three assessment points: pre-Mathematics Achievement Test (MAT), post-MAT, and post-post-MAT (retention), administered systematically by the researchers. Data collection utilized the established MAT instrument, which demonstrated a high reliability score of 0.86. Statistical analysis was conducted using the Statistical Package for Social Sciences (SPSS) version 28, with mean and standard deviation addressing study questions and analysis of covariance scrutinizing hypotheses at a significance level of .05. Results revealed significantly greater improvements in mathematics retention scores among students exposed to blended learning compared to those instructed through conventional methods. Moreover, noticeable differences in mean retention scores were observed, with male students in the blended learning group exhibiting notably higher performance. Based on these findings, recommendations were made, advocating for mathematics educators to integrate blended learning, particularly in geometry teaching, to enhance students’ retention of mathematical concepts.

Keywords: blended learning, flipped classroom model, secondary school students, station rotation model

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Authors: Mehrdad Hosseinishakib, Mozhgan Chakani, Gholamreza Babaei

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This study aims to investigate the relationship between the bilateral communication channels, communication technologies with effective communications and communication technologies, employee participation in motivated decision-making of employees using the EFQM excellence model in Education Organization of Area 4 in Karaj. This research is an applied research in terms of the purpose and is a descriptive survey research in terms of nature and method and assesses the current situation using field studies. The statistical population consists of all employees and managers of Education Organization of Area 4 in Karaj including 5442 persons and random sampling was used and sample size is 359 using Cochran formula. Measurement tool is a researcher-made questionnaire with 20 questions including two categories of expertise and general questions. The first category includes general questions about respondents' personal characteristics such as gender and level of education, work experience and courses of study. The second category includes expertise questions of the questionnaire that have been designed to test research hypotheses that its reliability was approved by Cronbach's alpha coefficient 0.916 and its validity was approved according to the vies of teachers and some senior managers of Education Organization of Area 4 in Karaj. The results of the analysis of the findings show that there is a significant relationship between mutual communication channels, communication technologies with effective communication between employees and management. There is also a significant relationship between communication technologies and employee motivation and employee participation in their motivated decision-making in Education Organization of Area 4 in Karaj.

Keywords: communication channels, effective communication, EFQM model, ANOVA

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Authors: Sunmaila Oyetunji Raimi, Olufemi Akinloye Bolaji, Abiodun Ezekiel Adesina

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The lingering poor performance of students in basic science spells doom for a vibrant scientific and technological development which pivoted the economic, social and physical upliftment of any nation. This calls for identifying appropriate strategies for imparting basic science knowledge and attitudes to the teaming youths in secondary schools. This study, therefore, determined the impact of computer mediated power point presentations on students’ achievement in basic science in Oyo State, Nigeria. A pre-test, posttest, control group quazi-experimental design adopted for the study. Two hundred and five junior secondary two students selected using stratified random sampling technique participated in the study. Three research questions and three hypotheses guided the study. Two evaluative instruments – Students’ Basic Science Attitudes Scale (SBSAS, r = 0.91); Students’ Knowledge of Basic Science Test (SKBST, r = 0.82) were used for data collection. Descriptive statistics of mean, standard deviation and inferential statistics of ANCOVA, scheffe post-hoc test were used to analyse the data. The results indicated significant main effect of treatment on students cognitive (F(1,200)= 171.680; p < 0.05) and attitudinal (F(1,200)= 34.466; p < 0.05) achievement in Basic science with the experimental group having higher mean gain than the control group. Gender has significant main effect (F(1,200)= 23.382; p < 0.05) on students cognitive outcomes but not significant for attitudinal achievement in Basic science. The study therefore recommended among others that computer mediated power point presentations should be incorporated into curriculum methodology of Basic science in secondary schools.

Keywords: basic science, computer mediated power point presentations, gender, students’ achievement

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Authors: Zahid Hussain, Nayyab Sultan

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This study describes the preparation of zinc oxide nanoparticles and their anti-diabetic effect individually and with the combination of Momordica charantia plant extract. This plant is termed bitter melon, balsam pear, bitter gourd, or karela. Blood glucose levels in mice were monitored in their random state before and after the administration of zinc oxide nanoparticles and plant extract. The powdered form of nanoparticles and the selected plant were used as an oral treatment. Diabetes was induced in mice by using a chemical named as streptozotocin. It is an artificial diabetes-inducing chemical. In the case of zinc oxide nanoparticles (3mg/kg) and Momordica charantia plant extract (500mg/kg); the maximum anti-diabetic effect observed was 70% ± 1.6 and 75% ± 1.3, respectively. In the case of the combination of zinc oxide nanoparticles (3mg/kg) and Momordica charantia plant extract (500mg/kg), the maximum anti-diabetic effect observed was 86% ± 2.0. The results obtained were more effective as compared to standard drugs Amaryl (3mg/kg), having an effectiveness of 52% ± 2.4, and Glucophage (500mg/kg), having an effectiveness of 29% ± 2.1. Results indicate that zinc oxide nanoparticles and plant extract in combination are more helpful in treating diabetes as compared to their individual treatments. It is considered a natural treatment without any side effects rather than using standard drugs, which shows adverse side effects on health, and most probably detoxifies in liver and kidneys. More experimental work and extensive research procedures are still required in order to make them applicable to pharmaceutical industries.

Keywords: albino mice, amaryl, anti-diabetic effect, blood glucose level, Camellia sinensis, diabetes mellitus, Momordica charantia plant extract, streptozotocin, zinc oxide nanoparticles

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Authors: Sebastian Töpfer, Marta Gilaberte Basset, Jorge Fuenzalida, Fabian Steinlechner, Juan P. Torres, Markus Gräfe

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This work introduces a combination of digital phase-shifting holography with a non-linear interferometer using undetected photons. Non-linear interferometers can be used in combination with a measurement scheme called quantum imaging with undetected photons, which allows for the separation of the wavelengths used for sampling an object and detecting it in the imaging sensor. This method recently faced increasing attention, as it allows to use of exotic wavelengths (e.g., mid-infrared, ultraviolet) for object interaction while at the same time keeping the detection in spectral areas with highly developed, comparable low-cost imaging sensors. The object information, including its transmission and phase influence, is recorded in the form of an interferometric pattern. To collect these, this work combines the method of quantum imaging with undetected photons with digital phase-shifting holography with a minimal sampling of the interference. With this, the quantum imaging scheme gets extended in its measurement capabilities and brings it one step closer to application. Quantum imaging with undetected photons uses correlated photons generated by spontaneous parametric down-conversion in a non-linear interferometer to create indistinguishable photon pairs, which leads to an effect called induced coherence without induced emission. Placing an object inside changes the interferometric pattern depending on the object’s properties. Digital phase-shifting holography records multiple images of the interference with determined phase shifts to reconstruct the complete interference shape, which can afterward be used to analyze the changes introduced by the object and conclude its properties. An extensive characterization of this method was done using a proof-of-principle setup. The measured spatial resolution, phase accuracy, and transmission accuracy are compared for different combinations of camera exposure times and the number of interference sampling steps. The current limits of this method are shown to allow further improvements. To summarize, this work presents an alternative holographic measurement method using non-linear interferometers in combination with quantum imaging to enable new ways of measuring and motivating continuing research.

Keywords: digital holography, quantum imaging, quantum holography, quantum metrology

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Authors: Louise Moles, Steve Riley, Sarah D. Lichenstein, Marzieh Babaeianjelodar, Robert Kohler, Annie Cheng, Corey Horien Abigail Greene, Wenjing Luo, Jonathan Ahern, Bohan Xu, Yize Zhao, Chun Chieh Fan, R. Todd Constable, Sarah W. Yip

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Background: Risks for depression are myriad and include both genetic and brain-based factors. However, relationships between these systems are poorly understood, limiting understanding of disease etiology, particularly at the developmental level. Methods: We use a data-driven machine learning approach connectome-based predictive modeling (CPM) to identify functional connectivity signatures associated with polygenic risk scores for depression (DEP-PRS) among youth from the Adolescent Brain and Cognitive Development (ABCD) study across diverse brain states, i.e., during resting state, during affective working memory, during response inhibition, during reward processing. Results: Using 10-fold cross-validation with 100 iterations and permutation testing, CPM identified connectivity signatures of DEP-PRS across all examined brain states (rho’s=0.20-0.27, p’s<.001). Across brain states, DEP-PRS was positively predicted by increased connectivity between frontoparietal and salience networks, increased motor-sensory network connectivity, decreased salience to subcortical connectivity, and decreased subcortical to motor-sensory connectivity. Subsampling analyses demonstrated that model accuracies were robust across random subsamples of N’s=1,000, N’s=500, and N’s=250 but became unstable at N’s=100. Conclusions: These data, for the first time, identify neural networks of polygenic depression risk in a large sample of youth before the onset of significant clinical impairment. Identified networks may be considered potential treatment targets or vulnerability markers for depression risk.

Keywords: genetics, functional connectivity, pre-adolescents, depression

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Authors: Laid Fekih

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Background: Depression affects people in all communities across the world and in all aspects of their lives. Its spread varies from one country to another, can happen at any age and get rid of it is not easy. There is no clear policy in Algeria's higher education institutions to detect and treat these disorders or pay particular attention to those at risk. Identifying the prevalence of depression among Algerian students, its correlation with different variables, and studying gender differences in the light of a range of variables is necessary to develop an appropriate plan to raise the level of hope and love of life among students. Method: Random samples of 1500 University of Tlemcen students (967 girls and 533 boys), aged 19 to 24 years completed a self-administered questionnaire that included Beck's Depression Inventory ®-II (BDI®-II), (School Health Promotion: The Mood part), Other questions included in this survey focused on demographic characteristics including gender, age and year of study, academic performance (Annual Average Score (0-20) AAS), were examined. Results: The rate of depression (moderate, severe and extreme) varied from 03% to 13% among university students in Tlemcen University. There was no difference in the rates of depression in male and female students, which means that male and female students do have similar rates of depression. The rate of depression in the first-year of the study shows a higher score relative to students of other years. Depression has a negative relationship with academic performance, which means that depressed students have many difficulties in academic tasks at university. Conclusion: Depression among university students is an important center of interest in the world, not only because of the ease with which they can be followed, or the difficulties encountered during their studies and their technical courses but for the link between the level of depression and the quality of care of mental health services, especially if many students with mood and emotional problems don't meet the criteria for psychotherapy.

Keywords: depression, epidemiology, university students, academic performance

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Authors: Erick R. Bandala, Kebret Kebede, Nicole Johnson, Rebecca Murray, Destiny Green, John Mejia, Polioptro Martinez-Austria

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Summertemperature data from Clark County was collected and used to estimate two different heat-related indexes: the heat index (HI) and excess heat factor (EHF). These two indexes were used jointly with data of health-related deaths in Clark County to assess the effect of extreme heat on the exposed population. The trends of the heat indexes were then analyzed for the 2007-2016 decadeandthe correlation between heat wave episodes and the number of heat-related deaths in the area was estimated. The HI showed that this value has increased significantly in June, July, and August over the last ten years. The same trend was found for the EHF, which showed a clear increase in the severity and number of these events per year. The number of heat wave episodes increased from 1.4 per year during the 1980-2016 period to 1.66 per yearduring the 2007-2016 period. However, a different trend was found for heat-wave-event duration, which decreasedfrom an average of 20.4 days during the trans-decadal period (1980-2016) to 18.1 days during the most recent decade(2007-2016). The number of heat-related deaths was also found to increase from 2007 to 2016, with 2016 with the highest number of heat-related deaths. Both HI and the number of deaths showeda normal-like distribution for June, July, and August, with the peak values reached in late July and early August. The average maximum HI values better correlated with the number of deaths registered in Clark County than the EHF, probably because HI uses the maximum temperature and humidity in its estimation,whereas EHF uses the average medium temperature. However, it is worth testing the EHF of the study zone because it was reported to fit properly in the case of heat-related morbidity. For the overall period, 437 heat-related deaths were registered in Clark County, with 20% of the deaths occurring in June, 52% occurring in July, 18% occurring in August,and the remaining 10% occurring in the other months of the year. The most vulnerable subpopulation was people over 50 years old, for which 76% of the heat-related deaths were registered.Most of the cases were associated with heart disease preconditions. The second most vulnerable subpopulation was young adults (20-50), which accounted for 23% of the heat-related deaths. These deathswere associated with alcoholic/illegal drug intoxication.

Keywords: heat, health, hazards, workforce

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Authors: Badawia Ibrahim, Iman Hussein, Samar El Sheikh, Fatma Abou Elkasem, Hazem Abo Ismael

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Background: Response of breast carcinoma to neoadjuvant chemotherapy (NAC) varies regarding many factors including hormonal receptor status. Breast cancer is a heterogenous disease with different outcomes, hence a need arises for new markers predicting the outcome of NAC especially for the triple negative group when estrogen, progesterone receptors and Her2/neu are negative. FOXP3 is a promising target with unclear role. Aim: To examine the value of FOXP3 expression in locally advanced triple negative breast cancer tumoral cells as well as tumor infiltrating lymphocytes (TILs) and to elucidate its relation to the extent of NAC response. Material and Methods: Forty five cases of immunohistochemically confirmed to be triple negative breast carcinoma were evaluated for NAC (Doxorubicin, Cyclophosphamide AC x 4 cycles + Paclitaxel x 12 weeks, patients with ejection fraction less than 60% received Taxotere or Cyclophosphamide, Methotrexate, Fluorouracil CMF) response in both tumour and lymph nodes status according to Miller & Payne's and Sataloff's systems. FOXP3 expression in tumor as well as TILs evaluated in the pretherapy biopsies was correlated with NAC response in breast tumor and lymph nodes as well as other clinicopathological factors. Results: Breast tumour cells showed FOXP3 positive cytoplasmic expression in (42%) of cases. High FOXP3 expression percentage was detected in (47%) of cases. High infiltration by FOXP3+TILs was detected in (49%) of cases. Positive FOXP3 expression was associated with negative lymph node metastasis. High FOXP3 expression percentage and high infiltration by FOXP3+TILs were significantly associated with complete therapy response in axillary lymph nodes. High FOXP3 expression in tumour cells was associated with high infiltration by FOXP3+TILs. Conclusion: This result may provide evidence that FOXP3 marker is a good prognostic and predictive marker for triple negative breast cancer (TNBC) indicated for neoadjuvant chemotherapy and can be used for stratifications of TNBC cases indicated for NAC. As well, this study confirmed the fact that the tumour cells and the surrounding microenvironment interact with each other and the tumour microenvironment can influence the treatment outcomes of TNBC.

Keywords: breast cancer, FOXP3 expression, prediction of neoadjuvant chemotherapy effect, triple negative

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Authors: Simon B. N. Thompson

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Early indicator of neurological disease has been proposed by the expanded Thompson Cortisol Hypothesis which suggests that yawning is linked to rises in cortisol levels. Cortisol is essential to the regulation of the immune system and pathological yawning is a symptom of multiple sclerosis (MS). Electromyography activity (EMG) in the jaw muscles typically rises when the muscles are moved – extended or flexed; and yawning has been shown to be highly correlated with cortisol levels in healthy people. It is likely that these elevated cortisol levels are also seen in people with MS. The possible link between EMG in the jaw muscles and rises in saliva cortisol levels during yawning were investigated in a randomized controlled trial of 60 volunteers aged 18-69 years who were exposed to conditions that were designed to elicit the yawning response. Saliva samples were collected at the start and after yawning, or at the end of the presentation of yawning-provoking stimuli, in the absence of a yawn, and EMG data was additionally collected during rest and yawning phases. Hospital Anxiety and Depression Scale, Yawning Susceptibility Scale, General Health Questionnaire, demographic, and health details were collected and the following exclusion criteria were adopted: chronic fatigue, diabetes, fibromyalgia, heart condition, high blood pressure, hormone replacement therapy, multiple sclerosis, and stroke. Significant differences were found between the saliva cortisol samples for the yawners, t (23) = -4.263, p = 0.000, as compared with the non-yawners between rest and post-stimuli, which was non-significant. There were also significant differences between yawners and non-yawners for the EMG potentials with the yawners having higher rest and post-yawning potentials. Significant evidence was found to support the Thompson Cortisol Hypothesis suggesting that rises in cortisol levels are associated with the yawning response. Further research is underway to explore the use of cortisol as a potential diagnostic tool as an assist to the early diagnosis of symptoms related to neurological disorders. Bournemouth University Research & Ethics approval granted: JC28/1/13-KA6/9/13. Professional code of conduct, confidentiality, and safety issues have been addressed and approved in the Ethics submission. Trials identification number: ISRCTN61942768. http://www.controlled-trials.com/isrctn/

Keywords: cortisol, electromyography, neurology, yawning

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Authors: Meghry Nazarian, Ibrahim Duyar

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Effective management of a diverse workforce in the United Arab Emirates (UAE) presents peculiar importance as two-thirds of residents are expatriates who have diverse ethnic and cultural backgrounds. Like any other organization in the country, UAE schools have become upmost diverse settings in the world. The purpose of this study was to examine whether principals’ cultural intelligence has direct and indirect (moderating) influences on teachers’ perceived diversity climate. A quantitative causal-comparative research design was employed to analyze the data. Participants included random samples of principals and teachers working in the private and charter schools in the Emirate of Abu Dhabi. The data-gathering online questionnaires included previously developed and validated scales as the measures of study variables. More specifically, the multidimensional short-form measure of Cultural Intelligence (CQ) and the diversity climate scale were used to measure the study variables. Multivariate statistics, including the analysis of multivariate analysis of variance (MANCOVA) and structural equation modeling (SEM), were employed to examine the relationships between the study variables. The preliminary analyses of data showed that principals and teachers have differing views of diversity management and climate in schools. Findings also showed that principals’ cultural intelligence has both direct and moderating influences on teachers’ perceived diversity climate. The study findings are expected to inform policymakers and practicing educational leaders in addressing diversity management in a country where the majority of the residents are the minority who have diverse ethnic and cultural backgrounds.

Keywords: diversity management, united arab emirates, school principals’ cultural intelligence (CQ), teachers’ perceived diversity climate

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Authors: Robert Long

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The results of a one-year study on the evolution of complexity, accuracy, and fluency (CAF) in the compositions of Japanese L2 university students throughout a semester are presented in this study. One goal was to determine if any improvement in writing abilities over this academic term had occurred, while another was to examine methods of editing. Participants had 30 minutes to write each essay with an additional 10 minutes allotted for editing. As for editing, participants were divided into two groups, one of which utilized an online grammar checker, while the other half self-edited their initial manuscripts. From the three different institutions, there was a total of 159 students. Research questions focused on determining if the CAF had evolved over the previous year, identifying potential variations in editing techniques, and describing the connections between the CAF dimensions. According to the findings, there was some improvement in accuracy (fewer errors) in all three of the measures), whereas there was a marked decline in complexity and fluency. As for the second research aim relating to the interaction among the three dimensions (CAF) and of possible increases in fluency being offset by decreases in grammatical accuracy, results showed (there is a logical high correlation with clauses and word counts, and mean length of T-unit (MLT) and (coordinate phrase of T-unit (CP/T) as well as MLT and clause per T-unit (C/T); furthermore, word counts and error/100 ratio correlated highly with error-free clause totals (EFCT). Issues of syntactical complexity had a negative correlation with EFCT, indicating that more syntactical complexity relates to decreased accuracy. Concerning a difference in error correction between those who self-edited and those who used an online grammar correction tool, results indicated that the variable of errors-free clause ratios (EFCR) had the greatest difference regarding accuracy, with fewer errors noted with writers using an online grammar checker. As for possible differences between the first and second (edited) drafts regarding CAF, results indicated there were positive changes in accuracy, the most significant change seen in complexity (CP/T and MLT), while there were relatively insignificant changes in fluency. Results also indicated significant differences among the three institutions, with Fujian University of Technology having the most fluency and accuracy. These findings suggest that to raise students' awareness of their overall writing development, teachers should support them in developing more complex syntactic structures, improving their fluency, and making more effective use of online grammar checkers.

Keywords: complexity, accuracy, fluency, writing

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Authors: Farah Ali, Tehreem Fayyaz, Musadiq Idris

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The present work was undertaken to investigate effects of various extracts of withania somnifera for anti-diabetic activity in alloxan induced diabetic rabbits. Rabbits were acclimatized for a week to standard laboratory temperature. Animals were fed according to a strict schedule (8 am, 3 pm and 10 pm) with green fodder (Medicago sativa) and tap water ad libitum. Animals were divided into nine groups of six rabbits each in a random manner. Body weights and physical activities of all rabbits were recorded before start of experiments. The animals of group 1 and 2 were given lactose (250 mg/kg, p.o) and Withania somniferaroot powder (100 mg/kg, p.o) respectively daily from day 1-20. Animals of group 3 were given alloxan (100 mg/kg, i.v) as a single dose on day 1. Powdered root of Withania somnifera in the doses of 100, 150, 200 mg/kg and its aqueous and ethanol extracts (equivalent to 200 mg/kg of crude drug) were given to the treated animals (groups 4-8), respectively by oral route for three weeks (day 1-20o.d), along with alloxan (100 mg/kg, i.v) as a single dose on day 1. Group 9 was treated with metformin (200 mg/kg, p.o) daily from day 1-20, along with a single dose of alloxan (100 mg/ kg, i.v) on day 1. Fasting serum glucose concentration in groups 3-9 was increased significantly (p<0.05) on day 3, with a maximum increase (215.3 mg/dl) in animals of toxic control (TC) group (3) on day 21 of the experiment as compared to normal control (NC) group (1). Effects of different doses (100, 150, 200 mg/kg, p.o) of W. somnifera root powder (WS) decreased the fasting serum glucose concentration as compared to toxic control group, with a maximum decrease (88.3 mg/dl) in group 2 (treated control) on day 21 of the experiment. Metformin (200 mg/kg, p.o) (reference control), aqueous extract (AWS) and ethanol extract (EWS) of W. somnifera (equivalent to 100 mg/kg W.somnifera root, p.o) antagonized the effects of alloxan as compared to toxic control group. These results indicate that the W. somnifera possess significant anti–diabetic activity.

Keywords: diabetes, serum, glucose, blood, sugar, rabbits

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Authors: A. K. Faizah, G. Vadamalai, S. K. Balasundram, W. L. Lim

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Pineapple (Ananas comosus) is a common crop in tropical and subtropical areas of the world. Malaysia once ranked as one of the top 3 pineapple producers in the world in the 60's and early 70's, after Hawaii and Brazil. Moreover, government’s recognition of the pineapple crop as one of priority commodities to be developed for the domestics and international markets in the National Agriculture Policy. However, pineapple industry in Malaysia still faces numerous challenges, one of which is the management of disease and pest. Red tip disease on pineapple was first recognized about 20 years ago in a commercial pineapple stand located in Simpang Renggam, Johor, Peninsular Malaysia. Since its discovery, there has been no confirmation on its causal agent of this disease. The epidemiology of red tip disease is still not fully understood. Nevertheless, the disease symptoms and the spread within the field seem to point toward viral infection. Bioassay test on nucleic acid extracted from the red tip-affected pineapple was done on Nicotiana tabacum cv. Coker by rubbing the extracted sap. Localised lesions were observed 3 weeks after inoculation. Negative staining of the fresh inoculated Nicotiana tabacum cv. Coker showed the presence of membrane-bound spherical particles with an average diameter of 94.25nm under transmission electron microscope. The shape and size of the particles were similar to tospovirus. SDS-PAGE analysis of partial purified virions from inoculated N. tabacum produced a strong and a faint protein bands with molecular mass of approximately 29 kDa and 55 kDa. Partial purified virions of symptomatic pineapple leaves from field showed bands with molecular mass of approximately 29 kDa, 39 kDa and 55kDa. These bands may indicate the nucleocapsid protein identity of tospovirus. Furthermore, a handheld sensor, Greenseeker, was used to detect red tip symptoms on pineapple non-destructively based on spectral reflectance, measured as Normalized Difference Vegetation Index (NDVI). Red tip severity was estimated and correlated with NDVI. Linear regression models were calibrated and tested developed in order to estimate red tip disease severity based on NDVI. Results showed a strong positive relationship between red tip disease severity and NDVI (r= 0.84).

Keywords: pineapple, diagnosis, virus, NDVI

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Authors: Xinqi Guo, Karen R. Dobkins

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Background and Objectives: Humans are probably the only animals whose minds are constantly filled with thoughts, feelings and emotions. Previous studies have investigated human minds from different dimensions, including its proportion of time for not being present, its representative format, its personal relevance, its temporal locus, and affect valence. The current study aims at characterizing human mind by employing Experience Sampling Methods (ESM), a self-report research procedure for studying daily experience. This study emphasis on answering the following questions: 1) How does the contents of the inner experience vary across demographics, 2) Are certain types of inner experiences correlated with level of mindfulness and mental well-being (e.g., are people who spend more time being present happier, and are more mindful people more at-present?), 3) Will being prompted to report one’s inner experience increase mindfulness and mental well-being? Methods: Participants were recruited from the subject pool of UC San Diego or from the social media. They began by filling out two questionnaires: 1) Five Facet Mindfulness Questionnaire-Short Form, and 2) Warwick-Edinburgh Mental Well-being Scale, and demographic information. Then they participated in the ESM part by responding to the prompts which contained questions about their real-time inner experience: if they were 'at-present', 'mind-wandering', or 'zoned-out'. The temporal locus, the clarity, and the affect valence, and the personal importance of the thought they had the moment before the prompt were also assessed. A mobile app 'RealLife Exp' randomly delivered these prompts 3 times/day for 6 days during wake-time. After the 6 days, participants completed questionnaire (1) and (2) again. Their changes of score were compared to a control group who did not participate in the ESM procedure (yet completed (1) and (2) one week apart). Results: Results are currently preliminary as we continue to collect data. So far, there is a trend that participants are present, mind-wandering and zoned-out, about 53%, 23% and 24% during wake-time, respectively. The thoughts of participants are ranked to be clearer and more neutral if they are present vs. mind-wandering. Mind-wandering thoughts are 66% about the past, consisting 80% of inner speech. Discussion and Conclusion: This study investigated the subjective account of human mind by a tool with high ecological validity. And it broadens the understanding of the relationship between contents of mind and well-being.

Keywords: experience sampling method, meta-memory, mindfulness, mind-wandering

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Authors: Fasil Wagnew, Kerri Viney, Kefyalew Addis Alene, Matthew Kelly, Darren Gray

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Background: Undernutrition is a risk factor for tuberculosis (TB), including poor treatment outcomes. However, evidence regarding the effect of undernutrition on TB treatment outcomes is not well understood. We aimed to evaluate the effect of undernutrition on sputum culture conversion and treatment outcomes among people with multi-drug resistance (MDR)-TB. Methods: We searched for publications in the Medline, Embase, Scopus, and Web of Science databases without restrictions on geography or year of publication. We conducted a random-effect meta-analysis to estimate the effects of undernutrition on sputum culture conversion and treatment outcomes. Two reviewers independently assessed the study eligibility, extracted the necessary information, and assessed the risk of bias. Depending on the nature of the data, odds ratio (OR) and hazard ratio (HR) with 95% confidence intervals (CIs) were used to summarize the effect estimates. Potential publication bias was checked using funnel plots and Egger’s tests. Results: Of 2358 records screened, 59 studies comprising a total of 31,254 people with MDR-TB were included. Undernutrition was significantly associated with a lower sputum culture conversion rate (HR 0·7, 95% CI 0·6–0·9, I2=67·1%) and a higher rate of mortality (OR 2·9, 95%CI 2·1–3·8, I2=23·7%) and unfavourable treatment outcomes (OR 1·8, 95%CI 1·5–2·0, I2=72·7%). There was no statistically significant publication bias in the included studies. Three studies were low, forty-two studies were moderate, and fourteen studies were high quality. Interpretations: Undernutrition was significantly associated with unfavourable treatment outcomes, including mortality and lower sputum culture conversion among people with MDR-TB. These findings have implications for supporting targeted nutritional interventions alongside standardised second-line TB drugs.

Keywords: undernutrition, MDR-TB, sputum culture conversion, treatment outcomes, meta-analysis

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Authors: B. O. Diyaolu

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The stadium transcends a field of play to cultural heritage of a club especially when there is security of life and property and a conducive environment with exciting media facilities, CCTV and adequate field of play. Football fans love watching their clubs’ matches especially when nothing discourages their presence in the stadium. This study investigated the influence of security on fans’ attendance during Nigeria Professional Football League matches. Descriptive survey research design was used and the population consists of all Nigeria Professional Football League fans. Simple random sampling technique was used to pick a state from the six geo-political zones. 600 respondents comprising male and female fans were sampled from the ten selected vendors’ stands in each selected state. A structured questionnaire on Security and Fan attendance scale (SFAS) was used. The instrument consists of two sections. Section A seeks information on demographic data of the respondents, while section B was used to elicit information on security and fans’ attendance. The modified instrument which consists of 20 items has a reliability coefficient of 0.73. The hypothesis was tested at 0.05 significance level. The completed questionnaire was collated, coded and analyzed using descriptive statistics of frequency counts and percentage and inferential statistics of chi-square (X²). Findings of this study revealed that adequate security significantly influences fan attendance during Nigeria Professional Football League matches. There is no sport that can develop if the facilities in use are inadequate. Improving the condition of the stadium in Nigeria is paramount to the development of the Nigeria Professional Football League. All stakeholders in the organization of the League must put into consideration the need to improve the standard of the stadium as it will help to increase the attendance of fans during matches. Only the standard ones should be used during matches.

Keywords: adequate security, fans attendance, football fans, football stadium, Nigeria professional football league

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Authors: Nico Rosamilia

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The study evaluates the importance of non-financial disclosure practices for regulators, investors, businesses, and markets. It aims to create a sector-specific set of indicators for environmental, social, and governance (ESG) performances alternative to the ratings of the agencies. The existing literature extensively studies the implementation of ESG rating systems. Conversely, this study has a twofold outcome. Firstly, it should generalize incentive systems and governance policies for ESG and sustainable principles. Therefore, it should contribute to the EU Sustainable Finance Disclosure Regulation. Secondly, it concerns the market and the investors by highlighting successful sustainable investing. Indeed, the study contemplates the effect of ESG adoption practices on corporate value. The research explores the asset pricing angle in order to shed light on the fragmented argument on the finance of ESG. Investors may be misguided about the positive or negative effects of ESG on performances. The paper proposes a different method to evaluate ESG performances. By comparing the results of a traditional econometric approach (Lasso) with a machine learning algorithm (Random Forest), the study establishes a set of indicators for ESG performance. Therefore, the research also empirically contributes to the theoretical strands of literature regarding model selection and variable importance in a finance framework. The algorithms will spit out sector-specific indicators. This set of indicators defines an alternative to the compounded scores of ESG rating agencies and avoids the possible offsetting effect of scores. With this approach, the paper defines a sector-specific set of indicators to standardize ESG disclosure. Additionally, it tries to shed light on the absence of a clear understanding of the direction of the ESG effect on corporate value (the problem of endogeneity).

Keywords: ESG ratings, non-financial information, value of firms, sustainable finance

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Authors: Zachary Huffman, Joana Rocha

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Wall-pressure fluctuations induced by the turbulent boundary layer (TBL) developed over aircraft are a significant source of aircraft cabin noise. Since the power spectral density (PSD) of these pressure fluctuations is directly correlated with the amount of sound radiated into the cabin, the development of accurate empirical models that predict the PSD has been an important ongoing research topic. The sound emitted can be represented from the pressure fluctuations term in the Reynoldsaveraged Navier-Stokes equations (RANS). Therefore, early TBL empirical models (including those from Lowson, Robertson, Chase, and Howe) were primarily derived by simplifying and solving the RANS for pressure fluctuation and adding appropriate scales. Most subsequent models (including Goody, Efimtsov, Laganelli, Smol’yakov, and Rackl and Weston models) were derived by making modifications to these early models or by physical principles. Overall, these models have had varying levels of accuracy, but, in general, they are most accurate under the specific Reynolds and Mach numbers they were developed for, while being less accurate under other flow conditions. Despite this, recent research into the possibility of using alternative methods for deriving the models has been rather limited. More recent studies have demonstrated that an artificial neural network model was more accurate than traditional models and could be applied more generally, but the accuracy of other machine learning techniques has not been explored. In the current study, an original model is derived using a stepwise regression algorithm in the statistical programming language R, and TBL wall-pressure fluctuations PSD data gathered at the Carleton University wind tunnel. The theoretical advantage of a stepwise regression approach is that it will automatically filter out redundant or uncorrelated input variables (through the process of feature selection), and it is computationally faster than machine learning. The main disadvantage is the potential risk of overfitting. The accuracy of the developed model is assessed by comparing it to independently sourced datasets.

Keywords: aircraft noise, machine learning, power spectral density models, regression models, turbulent boundary layer wall-pressure fluctuations

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Authors: Nkereke M. Essien

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The intention of this paper is to examine stress in the Educated Nigerian Accent of English (ENAE) with the aim of analyzing stress and rhythmic patterns of Nigerian English. Our aim also is to isolate differences and similarities in the stress patterns studied and also know what forms the accent of these Educated Nigerian English (ENE) which marks them off from other groups or English’s of the world, to ascertain and characterize it and to provide documented evidence for its existence. Nigerian stress and rhythmic patterns are significantly different from the British English stress and rhythmic patterns consequently, the educated Nigerian English (ENE) features more stressed syllables than the native speakers’ varieties. The excessive stressed of syllables causes a contiguous “Ss” in the rhythmic flow of ENE, and this brings about a “jerky rhythm’ which distorts communication. To ascertain this claim, ten (10) Nigerian speakers who are educated in the English Language were selected by a stratified Random Sampling technique from two Federal Universities in Nigeria. This classification belongs to the education to the educated class or standard variety. Their performance was compared to that of a Briton (control). The Metrical system of analysis was used. The respondents were made to read some words and utterance which was recorded and analyzed perceptually, statistically and acoustically using the one-way Analysis of Variance (ANOVA). The Turky-Kramer Post Hoc test, the Wilcoxon Matched Pairs Signed Ranks test, and the Praat analysis software were used in the analysis. It was revealed from our findings that the Educated Nigerian English speakers feature more stressed syllables in their productions by spending more time in pronouncing stressed syllables and sometimes lesser time in pronouncing the unstressed syllables. Their overall tempo was faster. The ENE speakers used tone to mark prominence while the native speaker used stress to mark pronounce, typified by the control. We concluded that the stress pattern of the ENE speakers was significantly different from the native speaker’s variety represented by the control’s performance.

Keywords: accent, Nigerian English, rhythm, stress

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Authors: Suraj Amrutkar, R. Gowri, Asma Khan, Nazam Khan, Vikas Mahajan, Manpreet Kour And Bharti Deshmukh

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Herbal additives are rich in vitamin C, A and other biological active compounds and may act as surrogate source to subdue heat stress in chicken. Among various herbal additives such as rough lemon (Citrus Jambhiri Lush) juice, amla (Emblica officinalis) juice and aloe vera (Aloe barbadensis miller) gel are easily available during summer (stress period) and also cost less as comparison to synthetic feed additives in market. In order to analyze the performance by supplementation of rough lemon juice, amla juice and aloe vera gel in broiler under heat stress conditions. Study was carried out with a random distribution of day old straight run chicks (240 No.) in to four treatment group (n=60) was done. All the groups were given basal diet (Maize-Soya based; T0) was same for all the groups with supplementation of rough lemon juice (T1), amla juice (T2) and aloe vera (T3) @ 2% in drinking water. Experiment trial lasted for 42 days during heat stress period (June-July) with minimum THI (78.2) and Maximum THI (88.02). Feed and water were offered ad-libitum throughout the trial. Results revealed significantly higher (P<0.05) body weight in T3 and T2, followed by T1 and least in T0 at 42 days of age. The overall mean of Feed conversion ratio of various treatment T0, T1, T2 andT3 were 2.16, 1.98, 1.89 and 1.82, respectively. The mortality percentage in various treatment, T0, T1, T2 and T3, were 6.67, 3.33, 0.0 and 1.67, respectively. pH value, PCV (%), Sodium (mmol/L) and Potassium (mmol/L) was higher in T3 than rest of the groups. HL ratio is significantly lower (P<0.05) in T3, T2 followed by T1 than T0 at 42 days of age. It may be inferred that amongst these phyto-additives, aloe vera leads in alleviating heat stress in broiler in an economical way, followed by amla and rough lemon.

Keywords: rough lemon, amla, aloe vera, heat stress, broiler

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Authors: Iman Farasat, Howard M. Salis

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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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Authors: Mateen A Khan, Taj Mohammad, Md. Imtaiyaz Hassan

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Alzheimer’s disease is characterized by the accumulation of the processing products of the amyloid beta peptide cleaved by amyloid precursor protein (APP). Iron increases the synthesis of amyloid beta peptides, which is why iron is present in Alzheimer's disease patients' amyloid plaques. Iron misregulation in the brain is linked to the overexpression of APP protein, which is directly related to amyloid-β aggregation in Alzheimer’s disease. The APP 5'-UTR region encodes a functional iron-responsive element (IRE) stem-loop that represents a potential target for modulating amyloid production. Targeted regulation of APP gene expression through the modulation of 5’-UTR sequence function represents a novel approach for the potential treatment of AD because altering APP translation can be used to improve both the protective brain iron balance and provide anti-amyloid efficacy. The molecular docking analysis of APP IRE RNA with eukaryotic translation initiation factors yields several models exhibiting substantial binding affinity. The finding revealed that the interaction involved a set of functionally active residues within the binding sites of eIF4F. Notably, APP IRE RNA and eIF4F interaction were stabilized by multiple hydrogen bonds with residues of APP IRE RNA and eIF4F. It was evident that APP IRE RNA exhibited a structural complementarity that tightly fit within binding pockets of eIF4F. The simulation studies further revealed the stability of the complexes formed between RNA and eIF4F, which is crucial for assessing the strength of these interactions and subsequent roles in the pathophysiology of Alzheimer’s disease. In addition, MD simulations would capture conformational changes in the IRE RNA and protein molecules during their interactions, illustrating the mechanism of interaction, conformational change, and unbinding events and how it may affect aggregation propensity and subsequent therapeutic implications. Our binding studies correlated well with the translation efficiency of APP mRNA. Overall, the outcome of this study suggests that the genomic modification and/or inhibiting the expression of amyloid protein by targeting APP IRE RNA can be a viable strategy to identify potential therapeutic targets for AD and subsequently be exploited for developing novel therapeutic approaches.

Keywords: Alzheimer's disease, Protein-RNA interaction analysis, molecular docking simulations, conformational dynamics, binding stability, binding kinetics, protein synthesis.

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