Search results for: optimal variation

Authors: Kuo Chieh Chao, Thishani Amarathunga, Sangam Shrestha

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Rainfall induced slope failures are one of the most damaging and disastrous natural hazards which occur frequently in the world. This type of sliding mainly occurs in the zone above the groundwater level in silty/sandy soils. When the rainwater begins to infiltrate into the vadose zone of the soil, the negative pore-water pressure tends to decrease and reduce the shear strength of soil material. Climate change has resulted in excessive and unpredictable rainfall in all around the world, resulting in landslides with dire consequences to human lives and infrastructure. Such problems could be overcome by examining in detail the causes for such slope failures and recommending effective repair plans for vulnerable locations by considering future climatic change. The selected area for this study is located in the road rehabilitation section from Maubara to Mota Ain road in Timor-Leste. Slope failures and cracks have occurred in 2013 and after repairs reoccurred again in 2017 subsequent to heavy rains. Both observed and future predicted climate data analyses were conducted to understand the severe precipitation conditions in past and future. Observed climate data were collected from NOAA global climate data portal. CORDEX data portal was used to collect Regional Climate Model (RCM) future predicted climate data. Both observed and RCM data were extracted to location-based data using ArcGIS Software. Linear scaling method was used for the bias correction of future data and bias corrected climate data were assigned to GeoStudio Software. Precipitations of wet seasons (December to March ) in 2007 to 2013 is higher than 2001-2006 period and it is more than nearly 40% higher precipitation than usual monthly average precipitation of 160mm.The results of seepage analyses which were carried out using SEEP/W model with observed climate, clearly demonstrated that the pore water pressure within the fill slope was significantly increased due to the increase of the infiltration during the wet season of 2013.One main Regional Climate Models (RCM) was analyzed in order to predict future climate variation under two Representative Concentration Pathways (RCPs).In the projected period of 76 years ahead from 2014, shows that the amount of precipitation is considerably getting higher in the future in both RCP 4.5 and RCP 8.5 emission scenarios. Critical pore water pressure conditions during 2014-2090 were used in order to recommend appropriate remediation methods. Results of slope stability analyses indicated that the factor of safety of the fill slopes was reduced from 1.226 to 0.793 during the dry season to wet season in 2013.Results of future slope stability which were obtained using SLOPE/W model for the RCP emissions scenarios depict that, the use of tieback anchors and geogrids in slope protection could be effective in increasing the stability of slopes to an acceptable level during the wet seasons. Moreover, methods and procedures like monitoring of slopes showing signs or susceptible for movement and installing surface protections could be used to increase the stability of slopes.

Keywords: climate change, precipitation, SEEP/W, SLOPE/W, unsaturated soil

Procedia PDF Downloads 134

Authors: A. Isahakyan, A. Terzyan, V. Stepanyan, N. Zulumyan, H. Beglaryan

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The involvement of silica hydrogel derived from serpentine minerals (Mg(Fe))6[Si4O10](OH)8 as a source of silicon dioxide in SiO2–NaOH–BaCl2–H2O system results in precipitating via one-hour stirring of boiling suspension such intermediates that on heating up to 800 °C crystallize into the product composed of barium ortho- Ba2SiO4 and metasilicates BaSiO3. Based on the positive results, this approach has been decided to be adapted to inserting europium (III) ions into the structure of the synthesized compounds. Intermediates previously precipitated in silica hydrogel–NaOH–BaCl2–Eu(NO3)3 system via one-hour stirring at room temperature underwent one-hour heat-treatment at different temperatures (6001200 °C). Prior to calcination, the suspension produced in the mixer was heated on a boiling-water bath until a powder-like sample was obtained. When the silica hydrogel was metered, SiO2 content in the silica hydrogel that is 5.8 % was taken into consideration in order to guaranty the molar ratios of both SiO2 to BaO and SiO2 to Na2O equal to 1:2. BaCl2 and Eu(NO3)3 reagents were weighted so that the formation of appropriate compositions was guaranteed. Samples including various concentrations of Eu3+ ions (1.25, 2.5, 3.75, 5, 6.35, 8.65, 10, 17.5, 18.75 and 20 mol%) were synthesized by the described method. Luminescence excitation, emission spectra of the products were recorded on the Agilent Cary Eclipes fluorescence spectrophotometer using Agilent Xenon flash lamp (80 Hz) as the excitation source (scanning rate=30 nm/min, excitation and emission slits width=5 nm, excitation filter set to auto, emission filter set to auto and PMT detector Voltage=800 V). Prior to optical properties measurements, each of the powder samples was put in the solid sample-holder. X-ray powder diffraction (XRPD) measurements were made on the SmartLab SE diffractometer. Emission spectra recorded for all the samples at an excitation wavelength of 394 nm exhibit peaks centered at around 536, 555, 587, 614, 653, 690 and 702.5 nm. The most intensive emission peak is observed at 614nm due to 5D0→7F2 of europium (III) ions transition. Luminescence intensity achieves its maximum for Eu3+ 17.5 mol% and heat-treatment at 1200 °C. The XRPD patterns revealed that the diffraction peaks recorded for this sample are identical to NaBa6Nd(SiO4)4 reflections. As Nd-containing reagents were not involved into the synthesis, the maximum luminescent intensity is most likely to be conditioned by NaBa6Eu(SiO4)4 formation whose reflections are not available in the ICDD-JCPDS database of crystallographic 2024. Up to Eu3+ 2.5 mol% the samples demonstrate the phases corresponding to Ba2SiO4 and BaSiO3 standards. Subsequent increasing of europium (III) concentration in the system leads to NaBa6Eu(SiO4)4 formation along with Ba2SiO4 and BaSiO3. NaBa6Eu(SiO4)4 share gradually increases and starting from 17.5 mol% and more NaBa6Eu(SiO4)4 phase is only registered. Thus, the variation of europium (III) concentration in silica hydrogel–NaOH–BaCl2–Eu(NO3)3 system allows producing by the precipitation method the products composed of europium (III)-doped Ba2SiO4 and BaSiO3 and/or NaBa6Eu(SiO4)4 distinguished by different luminescent properties. The work was supported by the Science Committee of RA, in the frames of the research projects № 21T-1D131 and № 21SCG-1D013.

Keywords: europium (III)-doped barium ortho- Ba2SiO4 and metasilicates BaSiO₃, NaBa₆Eu(SiO₄)₄, luminescence, precipitation method

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Authors: Vijaya Kumar, Vidayasagar Pagilla, Abraham Joshua, Rakshith Kedambadi, Prasanna Mithra

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Background: Post stroke rehabilitation are aimed to accelerate for optimal sensorimotor recovery, functional gain and to reduce long-term dependency. Intensive physical therapy interventions can enhance this recovery as experience-dependent neural plastic changes either directly act at cortical neural networks or at distal peripheral level (muscular components). Neuromuscular Electrical Stimulation (NMES), a traditional bottom-up approach, mirror therapy (MT), a relatively new top down approach have found to be an effective adjuvant treatment methods for lower extremity motor and functional recovery in stroke rehabilitation. However there is a scarcity of evidence to compare their therapeutic gain in stroke recovery.Aim: To compare the efficacy of neuromuscular electrical stimulation (NMES) and mirror therapy (MT) in very early phase of post stroke rehabilitation addressed to lower extremity motor recovery and balance. Design: observer blinded Randomized Clinical Trial. Setting: Neurorehabilitation Unit, Department of Physical Therapy, Tertiary Care Hospitals. Subjects: 32 acute stroke subjects with first episode of unilateral stroke with hemiparesis, referred for rehabilitation (onset < 3 weeks), Brunnstorm lower extremity recovery stages ≥3 and MMSE score more than 24 were randomized into two group [Group A-NMES and Group B-MT]. Interventions: Both the groups received eclectic approach to remediate lower extremity recovery which includes treatment components of Roods, Bobath and Motor learning approaches for 30 minutes a day for 6 days. Following which Group A (N=16) received 30 minutes of surface NMES training for six major paretic muscle groups (gluteus maximus and medius,quadriceps, hamstrings, tibialis anterior and gastrocnemius). Group B (N=16) was administered with 30 minutes of mirror therapy sessions to facilitate lower extremity motor recovery. Outcome measures: Lower extremity motor recovery, balance and activities of daily life (ADLs) were measured by Fugyl Meyer Assessment (FMA-LE), Berg Balance Scale (BBS), Barthel Index (BI) before and after intervention. Results: Pre Post analysis of either group across the time revealed statistically significant improvement (p < 0.001) for all the outcome variables for the either group. All parameters of NMES had greater change scores compared to MT group as follows: FMA-LE (25.12±3.01 vs. 23.31±2.38), BBS (35.12±4.61 vs. 34.68±5.42) and BI (40.00±10.32 vs. 37.18±7.73). Between the groups comparison of pre post values showed no significance with FMA-LE (p=0.09), BBS (p=0.80) and BI (p=0.39) respectively. Conclusion: Though either groups had significant improvement (pre to post intervention), none of them were superior to other in lower extremity motor recovery and balance among acute stroke subjects. We conclude that eclectic approach is an effective treatment irrespective of NMES or MT as an adjunct.

Keywords: balance, motor recovery, mirror therapy, neuromuscular electrical stimulation, stroke

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Authors: Anna Öqvist, Malin Malmström

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Attaining a higher level of education has become an increasingly important prerequisite for people’s economic and social independence and mobility. Young people who do not pursue higher education are not as attractive as potential employees in the modern work environment. Although completing a higher education degree is not a guarantee for getting a job, it substantially increases the chances for employment and, consequently, the chances for a better life. Despite this, it’s a fact that in several regions in Sweden, fewer students are choosing to engage in higher education. Similar trends have been emphasized in, for instance, the US where high dropout patterns among young people have been noted. This is a threat to future employment and industry development in these regions because the future employment base for society is dependent upon students’ willingness to invest in higher education. Much of prior studies have focused on the role of parents’ involvement in their children’s’ school work and the positive influence parents involvement have on their children’s school performance. Parental influence on education in general has been a topic of interest among those concerned with optimal developmental and educational outcomes for children and youth in pre-, secondary- and high school. Across a range of studies, there has emerged a strong conclusion that parental influence on child and youths education generally benefits children's and youths learning and school success. Arguably then, we could expect that parents influence on whether or not to pursue a higher education would be of importance to understand young people’s choice to engage in higher education. Accordingly, understanding what drives students’ intentions to pursue higher education is an essential component of motivating students to aspire to make the most of their potential in their future work life. Drawing on the theory of planned behavior, this study examines the role of parents influence on students’ attitudes about whether higher education can be beneficial to their future work life. We used a qualitative approach by collecting interview data from 18 high school students in Sweden to capture students’ cognitive and motivational mechanisms (attitudes) to influence intentions to engage in higher education. We found that parents may positively or negatively influence students’ attitudes and subsequently a student's intention to pursue higher education. Accordingly, our results show that parents’ own attitudes and expectations on their children are keys for influencing students’ attitudes and intentions for higher education. Further, our finding illuminates the mechanisms that drive students in one direction or the other. As such, our findings show that the same categories of arguments are used for driving students’ attitudes and intentions in two opposite directions, namely; financial arguments and work life benefits arguments. Our results contribute to existing literature by showing that parents do affect young people’s intentions to engage in higher studies. The findings contribute to the theory of planned behavior and have implications for the literature on higher education and educational psychology and also provide guidance on how to inform students about facts of higher studies in school.

Keywords: higher studies, intentions, parents influence, theory of planned behavior

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Authors: Irina Mizeva, Elena Potapova, Viktor Dremin, Mikhail Mezentsev, Valeri Shupletsov

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The local tissue perfusion is regulated by the microvascular tone which is under the control of a number of physiological mechanisms. Laser Doppler flowmetry (LDF) together with wavelet analyses is the most commonly used technique to study the regulatory mechanisms of cutaneous microcirculation. External factors such as temperature, local pressure of the probe on the skin, etc. influence on the blood flow characteristics and are used as physiological tests to evaluate microvascular regulatory mechanisms. Local probe pressure influences on the microcirculation parameters measured by optical methods: diffuse reflectance spectroscopy, fluorescence spectroscopy, and LDF. Therefore, further study of probe pressure effects can be useful to improve the reliability of optical measurement. During pressure tests variation of the mean perfusion measured by means of LDF usually is estimated. An additional information concerning the physiological mechanisms of the vascular tone regulation system in response to local pressure can be obtained using spectral analyses of LDF samples. The aim of the present work was to develop protocol and algorithm of data processing appropriate for study physiological response to the local pressure test. Involving 6 subjects (20±2 years) and providing 5 measurements for every subject we estimated intersubject and-inter group variability of response of both averaged and oscillating parts of the LDF sample on external surface pressure. The final purpose of the work was to find special features which further can be used in wider clinic studies. The cutaneous perfusion measurements were carried out by LAKK-02 (SPE LAZMA Ltd., Russia), the skin loading was provided by the originally designed device which allows one to distribute the pressure around the LDF probe. The probe was installed on the dorsal part of the distal finger of the index figure. We collected measurements continuously for one hour and varied loading from 0 to 180mmHg stepwise with a step duration of 10 minutes. Further, we post-processed the samples using the wavelet transform and traced the energy of oscillations in five frequency bands over time. Weak loading leads to pressure-induced vasodilation, so one should take into account that the perfusion measured under pressure conditions will be overestimated. On the other hand, we revealed a decrease in endothelial associated fluctuations. Further loading (88 mmHg) induces amplification of pulsations in all frequency bands. We assume that such loading leads to a higher number of closed capillaries, higher input of arterioles in the LDF signal and as a consequence more vivid oscillations which mainly are formed in arterioles. External pressure higher than 144 mmHg leads to the decrease of oscillating components, after removing the loading very rapid restore of the tissue perfusion takes place. In this work, we have demonstrated that local skin loading influence on the microcirculation parameters measured by optic technique; this should be taken into account while developing portable electronic devices. The proposed protocol of local loading allows one to evaluate PIV as far as to trace dynamic of blood flow oscillations. This study was supported by the Russian Science Foundation under project N 18-15-00201.

Keywords: blood microcirculation, laser Doppler flowmetry, pressure-induced vasodilation, wavelet analyses blood

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Authors: Emmanuel C. Ngerem

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The ever-increasing depletion of the dominant global form of energy (fossil fuels) calls for the development of sustainable and green alternative energy sources such as bioethanol, biohydrogen, and biodiesel. The production of the major biofuels relies on biomass feedstocks that are mainly derived from edible food crops and some inedible plants. One suitable feedstock with great potential as raw material for biofuel production is microalgal biomass. Despite the tremendous attributes of microalgae as a source of biofuel, their cultivation requires huge volumes of freshwater, thus posing a serious threat to commercial-scale production and utilization of algal biomass. In this study, a multi-media wastewater mixture for microalgae growth was formulated and optimized. Moreover, the obtained microalgae biomass was pre-treated to reduce sugar recovery and was compared with previous studies on microalgae biomass pre-treatment. The formulated and optimized mixed wastewater media for biomass and lipid accumulation was established using the simplex lattice mixture design. Based on the superposition approach of the potential results, numerical optimization was conducted, followed by the analysis of biomass concentration and lipid accumulation. The coefficients of regression (R²) of 0.91 and 0.98 were obtained for biomass concentration and lipid accumulation models, respectively. The developed optimization model predicted optimal biomass concentration and lipid accumulation of 1.17 g/L and 0.39 g/g, respectively. It suggested 64.69% dairy wastewater (DWW) and 35.31% paper and pulp wastewater (PWW) mixture for biomass concentration, 34.21% DWW, and 65.79% PWW for lipid accumulation. Experimental validation generated 0.94 g/L and 0.39 g/g of biomass concentration and lipid accumulation, respectively. The obtained microalgae biomass was pre-treated, enzymatically hydrolysed, and subsequently assessed for reducing sugars. The optimization of microwave pre-treatment of Chlorococcum sp. was achieved using response surface methodology (RSM). Microwave power (100 – 700 W), pre-treatment time (1 – 7 min), and acid-liquid ratio (1 – 5%) were selected as independent variables for RSM optimization. The optimum conditions were achieved at microwave power, pre-treatment time, and acid-liquid ratio of 700 W, 7 min, and 32.33:1, respectively. These conditions provided the highest amount of reducing sugars at 10.73 g/L. Process optimization predicted reducing sugar yields of 11.14 g/L on microwave-assisted pre-treatment of 2.52% HCl for 4.06 min at 700 watts. Experimental validation yielded reducing sugars of 15.67 g/L. These findings demonstrate that dairy wastewater and paper and pulp wastewater that could pose a serious environmental nuisance. They could be blended to form a suitable microalgae growth media, consolidating the potency of microalgae as a viable feedstock for fermentable sugars. Also, the outcome of this study supports the microalgal wastewater biorefinery concept, where wastewater remediation is coupled with bioenergy production.

Keywords: wastewater cultivation, mixture design, lipid, biomass, nutrient removal, microwave, Chlorococcum, raceway pond, fermentable sugar, modelling, optimization

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Authors: Babak Forouraghi

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A genetic circuit is a collection of interacting genes and proteins that enable individual cells to implement and perform vital biological functions such as cell division, growth, death, and signaling. In cell engineering, synthetic gene circuits are engineered networks of genes specifically designed to implement functionalities that are not evolved by nature. These engineered networks enable scientists to tackle complex problems such as engineering cells to produce therapeutics within the patient's body, altering T cells to target cancer-related antigens for treatment, improving antibody production using engineered cells, tissue engineering, and production of genetically modified plants and livestock. Construction of computational models to realize genetic circuits is an especially challenging task since it requires the discovery of the flow of genetic information in complex biological systems. Building synthetic biological models is also a time-consuming process with relatively low prediction accuracy for highly complex genetic circuits. The primary goal of this study was to investigate the utility of a pre-trained bidirectional encoder transformer that can accurately predict gene expressions in genetic circuit designs. The main reason behind using transformers is their innate ability (attention mechanism) to take account of the semantic context present in long DNA chains that are heavily dependent on the spatial representation of their constituent genes. Previous approaches to gene circuit design, such as CNN and RNN architectures, are unable to capture semantic dependencies in long contexts, as required in most real-world applications of synthetic biology. For instance, RNN models (LSTM, GRU), although able to learn long-term dependencies, greatly suffer from vanishing gradient and low-efficiency problem when they sequentially process past states and compresses contextual information into a bottleneck with long input sequences. In other words, these architectures are not equipped with the necessary attention mechanisms to follow a long chain of genes with thousands of tokens. To address the above-mentioned limitations, a transformer model was built in this work as a variation to the existing DNA Bidirectional Encoder Representations from Transformers (DNABERT) model. It is shown that the proposed transformer is capable of capturing contextual information from long input sequences with an attention mechanism. In previous works on genetic circuit design, the traditional approaches to classification and regression, such as Random Forrest, Support Vector Machine, and Artificial Neural Networks, were able to achieve reasonably high R2 accuracy levels of 0.95 to 0.97. However, the transformer model utilized in this work, with its attention-based mechanism, was able to achieve a perfect accuracy level of 100%. Further, it is demonstrated that the efficiency of the transformer-based gene expression classifier is not dependent on the presence of large amounts of training examples, which may be difficult to compile in many real-world gene circuit designs.

Keywords: machine learning, classification and regression, gene circuit design, bidirectional transformers

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Authors: Akbar Gharbali, Ali Abbasian Ardekani, Afshin Mohammadi

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Introduction: Thyroid nodules have an incidence of 33-68% in the general population. More than 5-15% of these nodules are malignant. Early detection and treatment of thyroid nodules increase the cure rate and provide optimal treatment. Between the medical imaging methods, Ultrasound is the chosen imaging technique for assessment of thyroid nodules. The confirming of the diagnosis usually demands repeated fine-needle aspiration biopsy (FNAB). So, current management has morbidity and non-zero mortality. Objective: To explore diagnostic potential of automatic texture analysis (TA) methods in differentiation benign and malignant thyroid nodules by ultrasound imaging in order to help for reliable diagnosis and monitoring of the thyroid nodules in their early stages with no need biopsy. Material and Methods: The thyroid US image database consists of 70 patients (26 benign and 44 malignant) which were reported by Radiologist and proven by the biopsy. Two slices per patient were loaded in Mazda Software version 4.6 for automatic texture analysis. Regions of interests (ROIs) were defined within the abnormal part of the thyroid nodules ultrasound images. Gray levels within an ROI normalized according to three normalization schemes: N1: default or original gray levels, N2: +/- 3 Sigma or dynamic intensity limited to µ+/- 3σ, and N3: present intensity limited to 1% - 99%. Up to 270 multiscale texture features parameters per ROIs per each normalization schemes were computed from well-known statistical methods employed in Mazda software. From the statistical point of view, all calculated texture features parameters are not useful for texture analysis. So, the features based on maximum Fisher coefficient and the minimum probability of classification error and average correlation coefficients (POE+ACC) eliminated to 10 best and most effective features per normalization schemes. We analyze this feature under two standardization states (standard (S) and non-standard (NS)) with Principle Component Analysis (PCA), Linear Discriminant Analysis (LDA) and Non-Linear Discriminant Analysis (NDA). The 1NN classifier was performed to distinguish between benign and malignant tumors. The confusion matrix and Receiver operating characteristic (ROC) curve analysis were used for the formulation of more reliable criteria of the performance of employed texture analysis methods. Results: The results demonstrated the influence of the normalization schemes and reduction methods on the effectiveness of the obtained features as a descriptor on discrimination power and classification results. The selected subset features under 1%-99% normalization, POE+ACC reduction and NDA texture analysis yielded a high discrimination performance with the area under the ROC curve (Az) of 0.9722, in distinguishing Benign from Malignant Thyroid Nodules which correspond to sensitivity of 94.45%, specificity of 100%, and accuracy of 97.14%. Conclusions: Our results indicate computer-aided diagnosis is a reliable method, and can provide useful information to help radiologists in the detection and classification of benign and malignant thyroid nodules.

Keywords: ultrasound imaging, thyroid nodules, computer aided diagnosis, texture analysis, PCA, LDA, NDA

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Authors: Muhammad Younas, Sidra Sawati, M. Razzaq Athar

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Organizational development history reveals that it has ever been a challenge to identify and fathom the role of talent management, career development and compensation management towards employees’ retention and organizational performance. Organizations strive hard to measure the impact of all those factors which affect employee retention and organizational performance. Researchers have worked in great deal in order to know the relationship of independent variables i.e. Talent Management, Career Development and Compensation Management on dependent variables i.e. Employee Retention and Organizational Performance. Employees adorned with latest skills with long lasting loyalty play a significant role towards successful achievement of short term as well as long term goals of the organizations. Retention of valuable and resourceful employees for a longer time is equally essential for meeting the set goals. The organizations which spend reasonable chunk of their resources for taking such measures that help to retain their employees through talent management and satisfactory career development always enjoy a competitive edge over their competitors. Human resource is regarded as one of the most precious and difficult resource to management. It has its own needs and requirement. It becomes an easy prey to monotony when lacks career development. Wants and aspirations of this resource are seldom met completely but can be managed through career development and compensation management. In this era of competition, organizations have to take viable steps to management their resources especially human resource. Top management and Managers keep on working for an amenable solution in order to address the challenges relating career development and compensation management as their ultimate goal is to ensure the organizational performance on optimum level. The current study was conducted to examine the impact of Talent Management, Career Development and Compensation Management towards Employees Retention and Organizational Performance with mediating effect of Employees Motivation in Service Sector of Pakistan. The current study is based on Resource Based View (RBV) and Ability Motivation Opportunity (AMO) theories. It explains that by increasing internal resources we can manage employee talent, career development through compensation management and employee motivation more effectively. It will result in effective execution of HRM practices for employee retention enabling an organization to achieve and sustain competitive advantage through optimal performance. Data collection was made through a structured questionnaire which was based upon adopted instruments after testing reliability and validity. A total 300 employees of 30 firms in service sector of Pakistan were sampled through non-probability sampling technique. Regression analysis revealed that talent management, career development and compensation management have significant positive impact on employee retention and perceived organizational performance. The results further showed that employee motivation have a significant mediating effect on employee retention and organizational performance. The interpretation of the findings and limitations, theoretical and managerial implications are also discussed.

Keywords: career development, compensation management, employee retention, organizational performance, talent management

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Authors: Yaroslav Pavlov

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In the modern world, ensuring quality has become increasingly important in various fields of human activity. One universal approach to quality management, proven effective in the food industry, is the HACCP (Hazard Analysis and Critical Control Points) concept. Based on principles of preventing potential hazards to consumers at all stages of production, from raw materials to the final product, HACCP offers a systematic approach to identifying, assessing risks, and managing critical control points (CCPs). Initially used primarily for food production, it was later effectively adapted to the food service sector. Implementing HACCP provides organizations with a reliable foundation for improving food safety, covering all links in the food chain from producer to consumer, making it an integral part of modern quality management systems. The main principles of HACCP—hazard identification, CCP determination, effective monitoring procedures, corrective actions, regular checks, and documentation—are universal and can be adapted to other areas. The adaptation of the HACCP concept is relevant for continuing professional education (CPE) with certain reservations. Specifically, it is reasonable to abandon the term ‘hazards’ as deviations in CCPs do not pose dangers, unlike in food production. However, the approach through CCP analysis and the use of HACCP's main principles for educational services are promising. This is primarily because it allows for identifying key CCPs based on the value creation model of a specific educational organization and consequently focusing efforts on specific CCPs to manage the quality of educational services. This methodology can be called the Analysis of Critical Points in Educational Services (ACPES). ACPES offers a similar approach to managing the quality of educational services, focusing on preventing and eliminating potential risks that could negatively impact the educational process, learners' achievement of set educational goals, and ultimately lead to students rejecting the organization's educational services. ACPES adapts proven HACCP principles to educational services, enhancing quality management effectiveness and student satisfaction. ACPES includes identifying potential problems at all stages of the educational process, from initial interest to graduation and career development. In ACPES, the term "hazards" is replaced with "problematic areas," reflecting the specific nature of the educational environment. Special attention is paid to determining CCPs—stages where corrective measures can most effectively prevent or minimize the risk of failing educational goals. The ACPES principles align with HACCP's principles, adjusted for the specificities of CPE. The method of the learner's journey map (variation of Customer Journey Map, CJM) can be used to overcome the complexity of formalizing the production chain in educational services. CJM provides a comprehensive understanding of the learner's experience at each stage, facilitating targeted and effective quality management. Thus, integrating the learner's journey map into ACPES represents a significant extension of the methodology's capabilities, ensuring a comprehensive understanding of the educational process and forming an effective quality management system focused on meeting learners' needs and expectations.

Keywords: quality management, continuing professional education, customer journey map, HACCP

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Authors: Devin Doos, Ashley Hughes, Trang Pham, Paul Barach, Rami Ahmed

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Over 115,000 Health Care Workers (HCWs) have died from COVID-19, and millions have been infected while caring for patients. HCWs have filed thousands of safety complaints surrounding safety concerns due to Personal Protective Equipment (PPE) shortages, which included concerns around inadequate and PPE reuse. Protocols for donning and doffing PPE remain ambiguous, lacking an evidence-base, and often result in wide deviations in practice. PPE donning and doffing protocol deviations commonly result in self-contamination but have not been thoroughly addressed. No evidence-driven protocols provide guidance on protecting HCW during periods of PPE reuse. Objective: The aim of this study was to examine safety-related threats and risks to Health Care Workers (HCWs) due to the reuse of PPE among Emergency Department personnel. Method: We conducted a prospective observational study to examine the risks of reusing PPE. First, ED personnel were asked to don and doff PPE in a simulation lab. Each participant was asked to don and doff PPE five times, according to the maximum reuse recommendation set by the Centers for Disease Control and Prevention (CDC). Each participant was videorecorded; video recordings were reviewed and coded independently by at least 2 of the 3trained coders for safety behaviors and riskiness of actions. A third coder was brought in when the agreement between the 2 coders could not be reached. Agreement between coders was high (81.9%), and all disagreements (100%) were resolved via consensus. A bowtie risk assessment chart was constructed analyzing the factors that contribute to increased risks HCW are faced with due to PPE use and reuse. Agreement amongst content experts in the field of Emergency Medicine, Human Factors, and Anesthesiology was used to select aspects of health care that both contribute and mitigate risks associated with PPE reuse. Findings: Twenty-eight clinician participants completed five rounds of donning/doffing PPE, yielding 140 PPE donning/doffing sequences. Two emerging threats were associated with behaviors in donning, doffing, and re-using PPE: (i) direct exposure to contaminant, and (ii) transmission/spread of contaminant. Protective behaviors included: hand hygiene, not touching the patient-facing surface of PPE, and ensuring a proper fit and closure of all PPE materials. 100% of participants (n= 28) deviated from the CDC recommended order, and most participants (92.85%, n=26) self-contaminated at least once during reuse. Other frequent errors included failure to tie all ties on the PPE (92.85%, n=26) and failure to wash hands after a contamination event occurred (39.28%, n=11). Conclusions: There is wide variation and regular errors in how HCW don and doffPPE while including in reusing PPE that led to self-contamination. Some errors were deemed “recoverable”, such as hand washing after touching a patient-facing surface to remove the contaminant. Other errors, such as using a contaminated mask and accidentally spreading to the neck and face, can lead to compound risks that are unique to repeated PPE use. A more comprehensive understanding of the contributing threats to HCW safety and complete approach to mitigating underlying risks, including visualizing with risk management toolsmay, aid future PPE designand workflow and space solutions.

Keywords: bowtie analysis, health care, PPE reuse, risk management

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Authors: M. G. Shilina

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The interstate economic interaction phenomenon is complex. ‘Economic integration’, as one of its types, can be explored through the prism of international law, the theories of the world economy, politics and international relations. The most objective study of the phenomenon requires a comprehensive multifactoral approach. In new geopolitical realities, the problems of coexistence and possible interconnection of various mechanisms of interstate economic interaction are actively discussed. Currently, the Eurasian continent states support the direction to economic integration. At the same time, the existing international economic law fragmentation in Eurasia is seen as the important problem. The Eurasian space is characterized by a various types of interstate relations: international agreements (multilateral and bilateral), and a large number of cooperation formats (from discussion platforms to organizations aimed at deep integration). For their harmonization, it is necessary to have a clear vision to the phased international economic relations regulation options. In the conditions of rapid development of international economic relations, the modeling (including prognostic) can be optimally used as the main scientific method for presenting the phenomenon. On the basis of this method, it is possible to form the current situation vision and the best options for further action. In order to determine the most objective version of the integration development, the combination of several approaches were used. The normative legal approach- the descriptive method of legal modeling- was taken as the basis for the analysis. A set of legal methods was supplemented by the international relations science prognostic methods. The key elements of the model are the international economic organizations and states' associations existing in the Eurasian space (the Eurasian Economic Union (EAEU), the European Union (EU), the Shanghai Cooperation Organization (SCO), Chinese project ‘One belt-one road’ (OBOR), the Commonwealth of Independent States (CIS), BRICS, etc.). A general term for the elements of the model is proposed - the interstate interaction mechanisms (IIM). The aim of building a model of current and future Eurasian economic integration is to show optimal options for joint economic development of the states and IIMs. The long-term goal of this development is the new economic and political space, so-called the ‘Great Eurasian Community’. The process of achievement this long-term goal consists of successive steps. Modeling the integration architecture and dividing the interaction into stages led us to the following conclusion: the SCO is able to transform Eurasia into a single economic space. Gradual implementation of the complex phased model, in which the SCO+ plays a key role, will allow building an effective economic integration for all its participants, to create an economically strong community. The model can have practical value for politicians, lawyers, economists and other participants involved in the economic integration process. A clear, systematic structure can serve as a basis for further governmental action.

Keywords: economic integration, The Eurasian Economic Union, The European Union, The Shanghai Cooperation Organization, The Silk Road Economic Belt

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Authors: Oliver Bertram, Leonel Akoto Chama

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In today's civil transport aircraft, the design of flight control systems is based on the experience gained from previous aircraft configurations with a clear distinction between primary and secondary flight control functions for controlling the aircraft altitude and trajectory. Significant system improvements are now seen particularly in multifunctional moveable concepts where the flight control functions are no longer considered separate but integral. This allows new functions to be implemented in order to improve the overall aircraft performance. However, the classical design process of flight controls is sequential and insufficiently interdisciplinary. In particular, the systems discipline is involved only rudimentarily in the early phase. In many cases, the task of systems design is limited to meeting the requirements of the upstream disciplines, which may lead to integration problems later. For this reason, approaching design with an incremental development is required to reduce the risk of a complete redesign. Although the potential and the path to multifunctional moveable concepts are shown, the complete re-engineering of aircraft concepts with less classic moveable concepts is associated with a considerable risk for the design due to the lack of design methods. This represents an obstacle to major leaps in technology. This gap in state of the art is even further increased if, in the future, unconventional aircraft configurations shall be considered, where no reference data or architectures are available. This means that the use of the above-mentioned experience-based approach used for conventional configurations is limited and not applicable to the next generation of aircraft. In particular, there is a need for methods and tools for a rapid trade-off between new multifunctional flight control systems architectures. To close this gap in the state of the art, an integrated system-driven design process for multifunctional flight control systems of non-classical aircraft configurations will be presented. The overall goal of the design process is to find optimal solutions for single or combined target criteria in a fast process from the very large solution space for the flight control system. In contrast to the state of the art, all disciplines are involved for a holistic design in an integrated rather than a sequential process. To emphasize the systems discipline, this paper focuses on the methodology for designing moveable actuation systems in the context of this integrated design process of multifunctional moveables. The methodology includes different approaches for creating system architectures, component design methods as well as the necessary process outputs to evaluate the systems. An application example of a reference configuration is used to demonstrate the process and validate the results. For this, new unconventional hydraulic and electrical flight control system architectures are calculated which result from the higher requirements for multifunctional moveable concept. In addition to typical key performance indicators such as mass and required power requirements, the results regarding the feasibility and wing integration aspects of the system components are examined and discussed here. This is intended to show how the systems design can influence and drive the wing and overall aircraft design.

Keywords: actuation systems, flight control surfaces, multi-functional movables, wing design process

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Authors: Nikola Góral, Piotr Mikołajczuk, Paweł Buczyński

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Much scientific research in the last 20 years has focused on the influence of global warming on the distribution and phenology of living organisms. Three potential responses to climate change are predicted: individual species may become extinct, adapt to new conditions in their existing range or change their range by migrating to places where climatic conditions are more favourable. It means not only migration to areas in other latitudes, but also different altitudes. In the case of dragonflies (Odonata), monitoring in Western Europe has shown that in response to global warming, dragonflies tend to change their range to a more northern one. The strongest response to global warming is observed in arctic and alpine species, as well as in species capable of migrating over long distances. The aim of the research was to assess whether the fauna of aquatic insects in high-mountain habitats has changed as a result of climate change and, if so, how big and what type these changes are. Dragonflies were chosen as a model organism because of their fast reaction to changes in the environment: they have high migration abilities and short life cycle. The state of the populations of boreal-mountain species and the extent to which lowland species entered high altitudes was assessed. The research was carried out on 20 sites in Western Sudetes, Southern Poland. They were located at an altitude of between 850 and 1250 m. The selected sites were representative of many types of valuable alpine habitats (subalpine raised bog, transitional spring bog, habitats associated with rivers and mountain streams). Several sites of anthropogenic origin were also selected. Thanks to this selection, a wide characterization of the fauna of the Karkonosze was made and it was compared whether the studied processes proceeded differently, depending on whether the habitat is primary or secondary. Both imagines and larvae were examined (by taking hydrobiological samples with a kick-net), and exuviae were also collected. Individual species dragonflies were characterized in terms of their reproductive, territorial and foraging behaviour. During each inspection, the basic physicochemical parameters of the water were measured. The population of the high-mountain dragonfly Somatochlora alpestris turned out to be in a good condition. This species was noted at several sites. Some of those sites were situated relatively low (995 m AMSL), which proves that the thermal conditions at the lower altitudes might be still optimal for this species. The protected by polish law species Somatochlora arctica, Aeshna subarctica and Leucorrhinia albifrons, as well as strongly associated with bogs Leucorrhinia dubia and Aeshna juncea bogs were observed. However, they were more frequent and more numerous in habitats of anthropogenic origin, which may suggest minor changes in the habitat preferences of dragonflies. The subject requires further research and observations over a longer time scale.

Keywords: alpine species, bioindication, global warming, habitat preferences, population dynamics

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Authors: Baha Eddine Aissou, Aichouche Belhadj Aissa

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Light detection and ranging (LiDAR) is an active remote sensing technology used for several applications. Airborne LiDAR is becoming an important technology for the acquisition of a highly accurate dense point cloud. A classification of airborne laser scanning (ALS) point cloud is a very important task that still remains a real challenge for many scientists. Support vector machine (SVM) is one of the most used statistical learning algorithms based on kernels. SVM is a non-parametric method, and it is recommended to be used in cases where the data distribution cannot be well modeled by a standard parametric probability density function. Using a kernel, it performs a robust non-linear classification of samples. Often, the data are rarely linearly separable. SVMs are able to map the data into a higher-dimensional space to become linearly separable, which allows performing all the computations in the original space. This is one of the main reasons that SVMs are well suited for high-dimensional classification problems. Only a few training samples, called support vectors, are required. SVM has also shown its potential to cope with uncertainty in data caused by noise and fluctuation, and it is computationally efficient as compared to several other methods. Such properties are particularly suited for remote sensing classification problems and explain their recent adoption. In this poster, the SVM classification of ALS LiDAR data is proposed. Firstly, connected component analysis is applied for clustering the point cloud. Secondly, the resulting clusters are incorporated in the SVM classifier. Radial basic function (RFB) kernel is used due to the few numbers of parameters (C and γ) that needs to be chosen, which decreases the computation time. In order to optimize the classification rates, the parameters selection is explored. It consists to find the parameters (C and γ) leading to the best overall accuracy using grid search and 5-fold cross-validation. The exploited LiDAR point cloud is provided by the German Society for Photogrammetry, Remote Sensing, and Geoinformation. The ALS data used is characterized by a low density (4-6 points/m²) and is covering an urban area located in residential parts of the city Vaihingen in southern Germany. The class ground and three other classes belonging to roof superstructures are considered, i.e., a total of 4 classes. The training and test sets are selected randomly several times. The obtained results demonstrated that a parameters selection can orient the selection in a restricted interval of (C and γ) that can be further explored but does not systematically lead to the optimal rates. The SVM classifier with hyper-parameters is compared with the most used classifiers in literature for LiDAR data, random forest, AdaBoost, and decision tree. The comparison showed the superiority of the SVM classifier using parameters selection for LiDAR data compared to other classifiers.

Keywords: classification, airborne LiDAR, parameters selection, support vector machine

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Authors: A. A. Purohit, M. M. Vaidya, M. D. Kudale

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Among the various developing countries in the world like China, Malaysia, Korea etc., India is also developing its infrastructures in the form of Road/Rail/Airports and Waterborne facilities at an exponential rate. Mumbai, the financial epicenter of India is overcrowded and to relieve the pressure of congestion, Navi Mumbai suburb is being developed on the east bank of Thane creek near Mumbai. The government due to limited space at existing Mumbai Airports (domestic and international) to cater for the future demand of airborne traffic, proposes to build a new international airport near Panvel at Navi Mumbai. Considering the precedence of extreme rainfall on 26^th July 2005 and nearby townships being in a low-lying area, wherein new airport is proposed, it is inevitable to study this complex confluence area from a hydrodynamic consideration under both tidal and extreme events (predicted discharge hydrographs), to avoid inundation of the surrounding due to the proposed airport reclamation (1160 hectares) and to determine the safe grade elevation (SGE). The model studies conducted using the application of unstructured mesh to simulate the Panvel estuarine area (93 km²), calibration, validation of a model for hydraulic field measurements and determine the maxima water levels around the airport for various extreme hydrodynamic events, namely the simultaneous occurrence of highest tide from the Arabian Sea and peak flood discharges (Probable Maximum Precipitation and 26^th July 2005) from five rivers, the Gadhi, Kalundri, Taloja, Kasadi and Ulwe, meeting at the proposed airport area revealed that: (a) The Ulwe River flowing beneath the proposed airport needs to be diverted. The 120m wide proposed Ulwe diversion channel having a wider base width of 200 m at SH-54 Bridge on the Ulwe River along with the removal of the existing bund in Moha Creek is inevitable to keep the SGE of the airport to a minimum. (b) The clear waterway of 80 m at SH-54 Bridge (Ulwe River) and 120 m at Amra Marg Bridge near Moha Creek is also essential for the Ulwe diversion and (c) The river bank protection works on the right bank of Gadhi River between the NH-4B and SH-54 bridges as well as upstream of the Ulwe River diversion channel are essential to avoid inundation of low lying areas. The maxima water levels predicted around the airport keeps SGE to a minimum of 11m with respect to Chart datum of Ulwe Bundar and thus development is not only technologically-economically feasible but also sustainable. The unstructured mesh modeling is a promising tool to simulate complex extreme hydrodynamic events and provides a reliable solution to evolve optimal SGE of airport.

Keywords: airport, hydrodynamics, safe grade elevation, tides

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Authors: Ghazal Faraj, András Micsik

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Shapes Constraint Language (SHACL), a World Wide Web Consortium (W3C) language, provides well-defined shapes and RDF graphs, named "shape graphs". These shape graphs validate other resource description framework (RDF) graphs which are called "data graphs". The structural features of SHACL permit generating a variety of conditions to evaluate string matching patterns, value type, and other constraints. Moreover, the framework of SHACL supports high-level validation by expressing more complex conditions in languages such as SPARQL protocol and RDF Query Language (SPARQL). SHACL includes two parts: SHACL Core and SHACL-SPARQL. SHACL Core includes all shapes that cover the most frequent constraint components. While SHACL-SPARQL is an extension that allows SHACL to express more complex customized constraints. Validating the efficacy of dataset mapping is an essential component of reconciled data mechanisms, as the enhancement of different datasets linking is a sustainable process. The conventional validation methods are the semantic reasoner and SPARQL queries. The former checks formalization errors and data type inconsistency, while the latter validates the data contradiction. After executing SPARQL queries, the retrieved information needs to be checked manually by an expert. However, this methodology is time-consuming and inaccurate as it does not test the mapping model comprehensively. Therefore, there is a serious need to expose a new methodology that covers the entire validation aspects for linking and mapping diverse datasets. Our goal is to conduct a new approach to achieve optimal validation outcomes. The first step towards this goal is implementing SHACL to validate the mapping between the International Committee for Documentation (CIDOC) conceptual reference model (CRM) and one of its ontologies. To initiate this project successfully, a thorough understanding of both source and target ontologies was required. Subsequently, the proper environment to run SHACL and its shape graphs were determined. As a case study, we performed SHACL over a CIDOC-CRM dataset after running a Pellet reasoner via the Protégé program. The applied validation falls under multiple categories: a) data type validation which constrains whether the source data is mapped to the correct data type. For instance, checking whether a birthdate is assigned to xsd:datetime and linked to Person entity via crm:P82a_begin_of_the_begin property. b) Data integrity validation which detects inconsistent data. For instance, inspecting whether a person's birthdate occurred before any of the linked event creation dates. The expected results of our work are: 1) highlighting validation techniques and categories, 2) selecting the most suitable techniques for those various categories of validation tasks. The next plan is to establish a comprehensive validation model and generate SHACL shapes automatically.

Keywords: SHACL, CIDOC-CRM, SPARQL, validation of ontology mapping

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Authors: Teimuraz Manjapharashvili, Ketevani Manjaparashvili

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Fuzzy logic is a modeling method for complex or ill-defined systems and is a relatively new mathematical approach. Its basis is to consider overlapping cases of parameter values and define operations to manipulate these cases. Fuzzy logic can successfully create operative automatic management or appropriate advisory systems. Fuzzy logic techniques in various operational control technologies have grown rapidly in the last few years. Fuzzy logic is used in many areas of human technological activity. In recent years, fuzzy logic has proven its great potential, especially in the automation of industrial process control, where it allows to form of a control design based on the experience of experts and the results of experiments. The engineering of chemical technological processes uses fuzzy logic in optimal management, and it is also used in process control, including the operational control of continuous cycle chemical industrial, technological processes, where special features appear due to the continuous cycle and correct management acquires special importance. This paper discusses how intelligent systems can be developed, in particular, how fuzzy logic can be used to build knowledge-based expert systems in chemical process engineering. The implemented projects reveal that the use of fuzzy logic in technological process control has already given us better solutions than standard control techniques. Fuzzy logic makes it possible to develop an advisory system for decision-making based on the historical experience of the managing operator and experienced experts. The present paper deals with operational control and management systems of continuous cycle chemical technological processes, including advisory systems. Because of the continuous cycle, many features are introduced in them compared to the operational control of other chemical technological processes. Among them, there is a greater risk of transitioning to emergency mode; the return from emergency mode to normal mode must be done very quickly due to the impossibility of stopping the technological process due to the release of defective products during this period (i.e., receiving a loss), accordingly, due to the need for high qualification of the operator managing the process, etc. For these reasons, operational control systems of continuous cycle chemical technological processes have been specifically discussed, as they are different systems. Special features of such systems in control and management were brought out, which determine the characteristics of the construction of control and management systems. To verify the findings, the development of an advisory decision-making information system for operational control of a lime kiln using fuzzy logic, based on the creation of a relevant expert-targeted knowledge base, was discussed. The control system has been implemented in a real lime production plant with a lime burn kiln, which has shown that suitable and intelligent automation improves operational management, reduces the risks of releasing defective products, and, therefore, reduces costs. The special advisory system was successfully used in the said plant both for the improvement of operational management and, if necessary, for the training of new operators due to the lack of an appropriate training institution.

Keywords: chemical process control systems, continuous cycle industrial technological processes, fuzzy logic, lime kiln

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Authors: Hai L. Tran

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When covering events and issues, the news media often employ both personal accounts as well as facts and figures. However, the process of using numbers and narratives in the newsroom is mostly operated through trial and error. There is a demonstrated need for the news industry to better understand the specific effects of storytelling and data-driven reporting on the audience as well as explanatory factors driving such effects. In the academic world, anecdotal evidence and statistical evidence have been studied in a mutually exclusive manner. Existing research tends to treat pertinent effects as though the use of one form precludes the other and as if a tradeoff is required. Meanwhile, narratives and statistical facts are often combined in various communication contexts, especially in news presentations. There is value in reconceptualizing and theorizing about both relative and collective impacts of numbers and narratives as well as the mechanism underlying such effects. The current undertaking seeks to link theory to practice by providing a complete picture of how and why people are influenced by information conveyed through quantitative and qualitative accounts. Specifically, the cognitive-experiential theory is invoked to argue that humans employ two distinct systems to process information. The rational system requires the processing of logical evidence effortful analytical cognitions, which are affect-free. Meanwhile, the experiential system is intuitive, rapid, automatic, and holistic, thereby demanding minimum cognitive resources and relating to the experience of affect. In certain situations, one system might dominate the other, but rational and experiential modes of processing operations in parallel and at the same time. As such, anecdotes and quantified facts impact audience response differently and a combination of data and narratives is more effective than either form of evidence. In addition, the present study identifies several media variables and human factors driving the effects of statistics and anecdotes. An integrative model is proposed to explain how message characteristics (modality, vividness, salience, congruency, position) and individual differences (involvement, numeracy skills, cognitive resources, cultural orientation) impact selective exposure, which in turn activates pertinent modes of processing, and thereby induces corresponding responses. The present study represents a step toward bridging theoretical frameworks from various disciplines to better understand the specific effects and the conditions under which the use of anecdotal evidence and/or statistical evidence enhances or undermines information processing. In addition to theoretical contributions, this research helps inform news professionals about the benefits and pitfalls of incorporating quantitative and qualitative accounts in reporting. It proposes a typology of possible scenarios and appropriate strategies for journalists to use when presenting news with anecdotes and numbers.

Keywords: data, narrative, number, anecdote, storytelling, news

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Authors: Alison C. Essary, Victor Trastek

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Introduction: The current state of the health care system in the U.S. is characterized by an unprecedented number of people living with multiple chronic conditions, unsustainable rise in health care costs, inadequate access to care, and wide variation in health outcomes throughout the country. An estimated two-thirds of Americans are living with two or more chronic conditions, contributing to 75% of all health care spending. In 2013, the School for the Science of Health Care Delivery (SHCD) was charged with redesigning the health care system through education and research. Faculty in business, law, and public policy, and thought leaders in health care delivery, administration, public health and health IT created undergraduate, graduate, and executive academic programs to address this pressing need. Faculty and students work across disciplines, and with community partners and employers to improve care delivery and increase value for patients. Methods: Curricula apply content in health care administration and operations within the clinical context. Graduate modules are team-taught by faculty across academic units to model team-based practice. Seminars, team-based assignments, faculty mentoring, and applied projects are integral to student success. Cohort-driven models enhance networking and collaboration. This observational study evaluated two years of admissions data, and one year of graduate data to assess program outcomes and inform the current graduate-level curricula. Descriptive statistics includes means, percentages. Results: Fall 2013, the program received 51 applications. The mean GPA of the entering class of 37 students was 3.38. Ninety-seven percent of the fall 2013 cohort successfully completed the program (n=35). Sixty-six percent are currently employed in the health care industry (n=23). Of the remaining 12 graduates, two successfully matriculated to medical school; one works in the original field of study; four await results on the MCAT or DAT, and five were lost to follow up. Attrition of one student was attributed to non-academic reasons. Fall 2014, the program expanded to include both on-ground and online cohorts. Applications were evenly distributed between on-ground (n=70) and online (n=68). Thirty-eight students enrolled in the on-ground program. The mean GPA was 3.95. Ninety-five percent of students successfully completed the program (n=36). Thirty-six students enrolled in the online program. The mean GPA was 3.85. Graduate outcomes are pending. Discussion: Challenges include demographic variability between online and on-ground students; yet, both profiles are similar in that students intend to become change agents in the health care system. In the past two years, on-ground applications increased by 31%, persistence to graduation is > 95%, mean GPA is 3.67, graduates report admission to six U.S. medical schools, the Mayo Medical School integrates SHCD content within their curricula, and there is national interest in collaborating on industry and academic partnerships. This places SHCD at the forefront of developing innovative curricula in order to improve high-value, patient-centered care.

Keywords: delivery science, education, health care delivery, high-value care, innovation in education, patient-centered

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Authors: Mukul Sharma, Madhusmita Das, Sundeep Chaitanya Vedithi

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Leprosy is a chronic human disease caused by Mycobacterium leprae, that cannot be cultured in vitro. Though treatable with multidrug therapy (MDT), recently, bacteria reported resistance to multiple antibiotics. Targeting DNA replication and repair pathways can serve as the foundation of developing new anti-leprosy drugs. Due to the absence of an axenic culture medium for the propagation of M. leprae, studying cellular processes, especially those belonging to DNA repair pathways, is challenging. Genomic understanding of M. Leprae harbors several protein-coding genes with no previously assigned function known as 'hypothetical proteins'. Here, we report identification and expression of known and hypothetical DNA repair genes from a human skin biopsy and mouse footpads that are involved in base excision repair, direct reversal repair, and SOS response. Initially, a bioinformatics approach was employed based on sequence similarity, identification of known protein domains to screen the hypothetical proteins in the genome of M. leprae, that are potentially related to DNA repair mechanisms. Before testing on clinical samples, pure stocks of bacterial reference DNA of M. leprae (NHDP63 strain) was used to construct standard graphs to validate and identify lower detection limit in the qPCR experiments. Primers were designed to amplify the respective transcripts, and PCR products of the predicted size were obtained. Later, excisional skin biopsies of newly diagnosed untreated, treated, and drug resistance leprosy cases from SIHR & LC hospital, Vellore, India were taken for the extraction of RNA. To determine the presence of the predicted transcripts, cDNA was generated from M. leprae mRNA isolated from clinically confirmed leprosy skin biopsy specimen across all the study groups. Melting curve analysis was performed to determine the integrity of the amplification and to rule out primer‑dimer formation. The Ct values obtained from qPCR were fitted to standard curve to determine transcript copy number. Same procedure was applied for M. leprae extracted after processing a footpad of nude mice of drug sensitive and drug resistant strains. 16S rRNA was used as positive control. Of all the 16 genes involved in BER, DR, and SOS, differential expression pattern of the genes was observed in terms of Ct values when compared to human samples; this was because of the different host and its immune response. However, no drastic variation in gene expression levels was observed in human samples except the nth gene. The higher expression of nth gene could be because of the mutations that may be associated with sequence diversity and drug resistance which suggests an important role in the repair mechanism and remains to be explored. In both human and mouse samples, SOS system – lexA and RecA, and BER genes AlkB and Ogt were expressing efficiently to deal with possible DNA damage. Together, the results of the present study suggest that DNA repair genes are constitutively expressed and may provide a reference for molecular diagnosis, therapeutic target selection, determination of treatment and prognostic judgment in M. leprae pathogenesis.

Keywords: DNA repair, human biopsy, hypothetical proteins, mouse footpads, Mycobacterium leprae, qPCR

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Authors: Pedro Llanos, Diego García

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Spaceflight is considered the last frontier in terms of science, technology, and engineering. But it is also the next frontier in terms of human physiology and performance. After more than 200,000 years humans have evolved under earth’s gravity and atmospheric conditions, spaceflight poses environmental stresses for which human physiology is not adapted. Hypoxia, accelerations, and radiation are among such stressors, our research involves suborbital flights aiming to develop effective countermeasures in order to assure sustainable human space presence. The physiologic baseline of spaceflight participants is subject to great variability driven by age, gender, fitness, and metabolic reserve. The objective of the present study is to characterize different physiologic variables in a population of STEM practitioners during an aerobatic flight. Cardiovascular and pulmonary responses were determined in Science Astronaut Candidates (SACs) during unusual attitude aerobatic flight indoctrination. Physiologic data recordings from 20 subjects participating in high-G flight training were analyzed. These recordings were registered by wearable sensor-vest that monitored electrocardiographic tracings (ECGs), signs of dysrhythmias or other electric disturbances during all the flight. The same cardiovascular parameters were also collected approximately 10 min pre-flight, during each high-G/unusual attitude maneuver and 10 min after the flights. The ratio (pre-flight/in-flight/post-flight) of the cardiovascular responses was calculated for comparison of inter-individual differences. The resulting tracings depicting the cardiovascular responses of the subjects were compared against the G-loads (Gs) during the aerobatic flights to analyze cardiovascular variability aspects and fluid/pressure shifts due to the high Gs. In-flight ECG revealed cardiac variability patterns associated with rapid Gs onset in terms of reduced heart rate (HR) and some scattered dysrhythmic patterns (15% premature ventricular contractions-type) that were considered as triggered physiological responses to high-G/unusual attitude training and some were considered as instrument artifact. Variation events were observed in subjects during the +Gz and –Gz maneuvers and these may be due to preload and afterload, sudden shift. Our data reveal that aerobatic flight influenced the breathing rate of the subject, due in part by the various levels of energy expenditure due to the increased use of muscle work during these aerobatic maneuvers. Noteworthy was the high heterogeneity in the different physiological responses among a relatively small group of SACs exposed to similar aerobatic flights with similar Gs exposures. The cardiovascular responses clearly demonstrated that SACs were subjected to significant flight stress. Routine ECG monitoring during high-G/unusual attitude flight training is recommended to capture pathology underlying dangerous dysrhythmias in suborbital flight safety. More research is currently being conducted to further facilitate the development of robust medical screening, medical risk assessment approaches, and suborbital flight training in the context of the evolving commercial human suborbital spaceflight industry. A more mature and integrative medical assessment method is required to understand the physiology state and response variability among highly diverse populations of prospective suborbital flight participants.

Keywords: g force, aerobatic maneuvers, suborbital flight, hypoxia, commercial astronauts

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Authors: Dalila Chaid, Bennameur Fedilli, Mohammed Amine Bellelou

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The study focuses on the experience of lower-limb amputees, who face both physical and psychological challenges due to their disability. Chronic neuropathic pain and various types of limb pain are common in these patients. They often require orthopaedic interventions for issues such as dressings, infection, ulceration, and bone-related problems. Research Aim: The aim of this study is to determine the most suitable anaesthetic technique for lower-limb amputees, which can provide them with the greatest comfort and prolonged analgesia. The study also aims to demonstrate the effectiveness and cost-effectiveness of ultrasound-guided local regional anaesthesia (LRA) in this patient population. Methodology: The study is an observational analytical study conducted over a period of eight years, from 2010 to 2018. It includes a total of 955 cases of revisions performed on lower limb stumps. The parameters analyzed in this study include the effectiveness of the block and the use of sedation, the duration of the block, the post-operative visual analog scale (VAS) scores, and patient comfort. Findings: The study findings highlight the benefits of ultrasound-guided LRA in providing comfort by optimizing post-operative analgesia, which can contribute to psychological and bodily repair in lower-limb amputees. Additionally, the study emphasizes the use of alpha2 agonist adjuvants with sedative and analgesic properties, long-acting local anaesthetics, and larger volumes for better outcomes. Theoretical Importance: This study contributes to the existing knowledge by emphasizing the importance of choosing an appropriate anaesthetic technique for lower-limb amputees. It highlights the potential of ultrasound-guided LRA and the use of specific adjuvants and local anaesthetics in improving post-operative analgesia and overall patient outcomes. Data Collection and Analysis Procedures: Data for this study were collected through the analysis of medical records and relevant documentation related to the 955 cases included in the study. The effectiveness of the anaesthetic technique, duration of the block, post-operative pain scores, and patient comfort were analyzed using statistical methods. Question Addressed: The study addresses the question of which anaesthetic technique would be most suitable for lower-limb amputees to provide them with optimal comfort and prolonged analgesia. Conclusion: The study concludes that ultrasound-guided LRA, along with the use of alpha2 agonist adjuvants, long-acting local anaesthetics, and larger volumes, can be an effective approach in providing comfort and improving post-operative analgesia for lower-limb amputees. This technique can potentially contribute to the psychological and bodily repair of these patients. The findings of this study have implications for clinical practice in the management of lower-limb amputees, highlighting the importance of personalized anaesthetic approaches for better outcomes.

Keywords: neuropathic pain, ultrasound-guided peripheral nerve block, DN4 quiz, EMG

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Authors: L. Abubakar, B. M. Sokoto, I. U. Mohammed, M. S. Na’allah, A. Mohammad, A. N. Garba, T. S. Bubuche

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Onion (Allium cepa var. cepa L.), is the most important species of the Allium group belonging to family Alliaceae and genus Allium. It can be regarded as the single important vegetable species in the world after tomatoes. Despite the similarities, which bring the species together, the genus is a strikingly diverse one, with more than five hundred species, which are perennial and mostly bulbous plants. Out of these, only seven species are in cultivation, and five are the most important species of the cultivated Allium. However, Allium cepa (onion) and Allium sativum (Garlic) are the two major cultivated species grown all over the world of which the onion crop is the most important. Heritability defined as the proportion of the observed total variability that is genetic, and its estimates from variance components give more useful information of genotypic variation from the total phenotypic differences and environmental effects on the individuals or families. It therefore guide the breeder with respect to the ease with which selection of traits can be carried out. Heritability estimates guide the breeder with respect to ease of selection of traits while correlations suggest how selection among characters can be practiced. Correlations explain relationship between characters and suggest how selection among characters can be practiced in breeding programmes. Highly significant correlations have been reported, between yield, maturity, rings/bulb and storage loss in onions. Similarly significant positive correlation exists between total bulb yield and plant height, leaf number/plant, bulb diameter and bulb yield/plant. Moderate positive correlations have been observed between maturity date and yield, dry matter content was highly correlated with soluble solids, and higher correlations were also observed between storage loss and soluble solids. The objective of the study is to determine heritability estimates and correlations for characters among onion cultivars of North Western Nigeria. This is envisaged will assist in the breeding of superior onion cultivars within the zone. Thirteen onion cultivars were collected during an expedition covering north western Nigeria and Southern part of Niger Republic during 2013, which are areas noted for onion production. The cultivars were evaluated at two locations; Sokoto, in Sokoto State and Jega in Kebbi State all in Nigeria during the 2013/14 onion season (dry season) under irrigation. Combined analysis of the results revealed fresh bulb yield is highly significantly positively correlated with bulb height and cured bulb yield, and significant positive correlation with plant height and bulb diameter. It also recorded significant negative correlation with mean No. of leaves/plant and non significant negative correlation with bolting %. Cured bulb yield (marketable yield) had highly significant positive correlation with mean bulb weight and fresh bulb yield/ha, with significant positive correlation with bulb height. It also recorded highly significant negative correlation with No. of leaves/plant and significant negative correlation with bolting % and non significant positive correlation with plant height and non significant negative correlation with bulb diameter. High broad sense heritability estimates were recorded for plant height, fresh bulb yield, number of leaves/plant, bolting % and cured bulb yield. Medium to low broad sense heritabilities were also observed for mean bulb weight, plant height and bulb diameter.

Keywords: correlation, heritability, onions, North Western Nigeria

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Authors: D. Pogliana, A. Maso, N. Milani, D. Panzin, S. Rivaroli, J. Konin

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This case aims to identify the role of movement quality during the final stage of return to sport (RTS) in a male amateur football player 13 years old after passing the acute phase of the bilateral Osgood-Schlatter disease (OSD). The patient, after a year from passing the acute phase of OSD with the abstention of physical activity, reports bilateral anterior knee pain at the beginning of the football sport activity. Interventions: After the orthopedist check, who recommended physiotherapy sessions for the correction of motor patterns and the isometric reinforcement of the muscles of the quadriceps, the rehabilitation intervention was developed in 7 weeks through 14 sessions of neuro-motor training (NMT) with a frequency of two weekly sessions and six sessions of muscle-strengthening with a frequency of one weekly session. The sessions of NMT were carried out through free body exercises (or with overloads) with visual bio-feedback with the help of two cameras (one with anterior vision and one with lateral vision of the subject) and a big touch screen. The aim of these sessions of NMT was to modify the dysfunctional motor patterns evaluated by the 2D motion analysis test. The test was carried out at the beginning and at the end of the rehabilitation course and included five movements: single-leg squat (SLS), drop jump (DJ), single-leg hop (SLH), lateral shuffle (LS), and change of direction (COD). Each of these movements was evaluated through the video analysis of dynamic valgus knee, pelvic tilt, trunk control, shock absorption, and motor strategy. A free image analysis software (Kinovea) was then used to calculate scores. Results: Baseline assessment of the subject showed a total score of 59% on the right limb and 64% on the left limb (considering an optimal score above 85%) with large deficits in shock absorption capabilities, the presence of dynamic valgus knee, and dysfunctional motor strategies defined “quadriceps dominant.” After six weeks of training, the subject achieved a total score of 80% on the right limb and 86% on the left limb, with significant improvements in shock absorption capabilities, the presence of dynamic knee valgus, and the employment of more hip-oriented motor strategies on both lower limbs. The improvements shown in dynamic knee valgus, greater hip-oriented motor strategies, and improved shock absorption identified through six weeks of the NMT program can help a teenager amateur football player to manage the anterior knee pain during sports activity. In conclusion, NMT was a good choice to help a 13 years old male amateur football player to return to performance without pain after OSD and can also be used with all this type of athletes of the other teams' sports.

Keywords: movement analysis, neuro-motor training, knee pain, movement strategies

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Authors: Gail Schofield, Antoine M. Dujon, Nicole Esteban, Rebecca M. Lester, Graeme C. Hays

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Variation in diel movement patterns during migration provides information on the strategies used by animals to maximize energy efficiency and ensure the successful completion of migration. For instance, many flying and land-based terrestrial species stop to rest and refuel at regular intervals along the migratory route, or at transitory ‘stopover’ sites, depending on resource availability. However, in cases where stopping is not possible (such as over–or through deep–open oceans, or over deserts and mountains), non-stop travel is required, with animals needing to develop strategies to rest while actively traveling. Recent advances in biologging technologies have identified mid-flight micro sleeps by swifts in Africa during the 10-month non-breeding period, and the use of lateralized sleep behavior in orca and bottlenose dolphins during migration. Here, highly accurate locations obtained by Argos-linked Fastloc-GPS transmitters of adult green (n=8 turtles, 9487 locations) and loggerhead (n=46 turtles, 47,588 locations) sea turtles migrating around thousand kilometers (over several weeks) from breeding to foraging grounds across the Indian and Mediterranean oceans were used to identify potential resting strategies. Stopovers were only documented for seven turtles, lasting up to 6 days; thus, this strategy was not commonly used, possibly due to the lack of potential ‘shallow’ ( < 100 m seabed depth) sites along routes. However, observations of the day versus night speed of travel indicated that turtles might use other mechanisms to rest. For instance, turtles traveled an average 31% slower at night compared to day during oceanic crossings. Slower travel speeds at night might be explained by turtles swimming in a less direct line at night and/or deeper dives reducing their forward motion, as indicated through studies using Argos-linked transmitters and accelerometers. Furthermore, within the first 24 h of entering waters shallower than 100 m towards the end of migration (the depth at which sea turtles can swim and rest on the seabed), some individuals travelled 72% slower at night, repeating this behavior intermittently (each time for a one-night duration at 3–6-day intervals) until reaching the foraging grounds. If the turtles were, in fact, resting on the seabed at this point, they could be inactive for up to 8-hours, facilitating protracted periods of rest after several weeks of constant swimming. Turtles might not rest every night once within these shallower depths, due to the time constraints of reaching foraging grounds and restoring depleted energetic reserves (as sea turtles are capital breeders, they tend not to feed for several months during migration to and from the breeding grounds and while breeding). In conclusion, access to data-rich, highly accurate Argos-linked Fastloc-GPS provided information about differences in the day versus night activity at different stages of migration, allowing us, for the first time, to compare the strategies used by a marine vertebrate with terrestrial land-based and flying species. However, the question of what resting strategies are used by individuals that remain in oceanic waters to forage, with combinations of highly accurate Argos-linked Fastloc-GPS transmitters and accelerometry or time-depth recorders being required for sufficient numbers of individuals.

Keywords: argos-linked fastloc GPS, data loggers, migration, resting strategy, telemetry

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

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

Keywords: bioelectrochemistry, aptasensors, single-cell, nanopillars

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Authors: Avdhesh K. Sharma

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Key, in the development of energy-efficient micro-scale heat exchanger devices, is to select large heat transfer surface to volume ratio without much expanse on re-circulated pumps. The increased interest in short heat exchanger (SHE) is due to accessibility of advanced technologies for manufacturing of micro-tubes in range of 1 micron m - 1 mm. Such SHE using micro-tubes are highly effective for high flux heat transfer technologies. Nanofluids, are used to enhance the thermal conductivity of re-circulated coolant and thus enhances heat transfer rate further. Higher viscosity associated with nanofluid expands more pumping power. Thus, there is a trade-off between heat transfer rate and pressure drop with geometry of micro-tubes. Herein, a novel design of short counter flow heat exchanger (SCFHE) using non-circular micro-tubes flooded with CuO-water nanofluid is conceptualized by varying the ratio of surface area to cross-sectional area of micro-tubes. A framework for comparative analysis of SCFHE using micro-tubes non-circular shape flooded by CuO-water nanofluid is presented. In SCFHE concept, micro-tubes having various geometrical shapes (viz., triangular, rectangular and trapezoidal) has been arranged row-wise to facilitate two aspects: (1) allowing easy flow distribution for cold and hot stream, and (2) maximizing the thermal interactions with neighboring channels. Adequate distribution of rows for cold and hot flow streams enables above two aspects. For comparative analysis, a specific volume or cross-section area is assigned to each elemental cell (which includes flow area and area corresponds to half wall thickness). A specific volume or cross-section area is assumed to be constant for each elemental cell (which includes flow area and half wall thickness area) and variation in surface area is allowed by selecting different geometry of micro-tubes in SCFHE. Effective thermal conductivity model for CuO-water nanofluid has been adopted, while the viscosity values for water based nanofluids are obtained empirically. Correlations for Nusselt number (Nu) and Poiseuille number (Po) for micro-tubes have been derived or adopted. Entrance effect is accounted for. Thermal and hydrodynamic performances of SCFHE are defined in terms of effectiveness and pressure drop or pumping power, respectively. For defining the overall performance index of SCFHE, two links are employed. First one relates heat transfer between the fluid streams q and pumping power PP as (=qj/PPj); while another link relates effectiveness eff and pressure drop dP as (=effj/dPj). For analysis, the inlet temperatures of hot and cold streams are varied in usual range of 20dC-65dC. Fully turbulent regime is seldom encountered in micro-tubes and transition of flow regime occurs much early (i.e., ~Re=1000). Thus, Re is fixed at 900, however, the uncertainty in Re due to addition of nanoparticles in base fluid is quantified by averaging of Re. Moreover, for minimizing error, volumetric concentration is limited to range 0% to ≤4% only. Such framework may be helpful in utilizing maximum peripheral surface area of SCFHE without any serious severity on pumping power and towards developing advanced short heat exchangers.

Keywords: CuO-water nanofluid, non-circular micro-tubes, performance index, short counter flow heat exchanger

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Authors: Danjuma Bawa

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This paper aimed at exploring the capabilities of Location-Allocation model in complementing the strides of the existing physical planning models in the location and distribution of facilities for regional consumption. The paper was designed to provide a blueprint to the Nigerian government and other donor agencies especially the Fertilizer Distribution Initiative (FDI) by the federal government for the revitalization of the terrorism ravaged regions. Theoretical underpinnings of central place theory related to spatial distribution, interrelationships, and threshold prerequisites were reviewed. The study showcased how Location-Allocation Model (L-AM) alongside Central Place Theory (CPT) was applied in Geographic Information System (GIS) environment to; map and analyze the spatial distribution of settlements; exploit their physical and economic interrelationships, and to explore their hierarchical and opportunistic influences. The study was purely spatial qualitative research which largely used secondary data such as; spatial location and distribution of settlements, population figures of settlements, network of roads linking them and other landform features. These were sourced from government ministries and open source consortium. GIS was used as a tool for processing and analyzing such spatial features within the dictum of CPT and L-AM to produce a comprehensive spatial digital plan for equitable and judicious location and distribution of fertilizer deports in the study area in an optimal way. Population threshold was used as yardstick for selecting suitable settlements that could stand as service centers to other hinterlands; this was accomplished using the query syntax in ArcMapTM. ArcGISTM’ network analyst was used in conducting location-allocation analysis for apportioning of groups of settlements around such service centers within a given threshold distance. Most of the techniques and models ever used by utility planners have been centered on straight distance to settlements using Euclidean distances. Such models neglect impedance cutoffs and the routing capabilities of networks. CPT and L-AM take into consideration both the influential characteristics of settlements and their routing connectivity. The study was undertaken in two terrorism ravaged Local Government Areas of Adamawa state. Four (4) existing depots in the study area were identified. 20 more depots in 20 villages were proposed using suitability analysis. Out of the 300 settlements mapped in the study area about 280 of such settlements where optimally grouped and allocated to the selected service centers respectfully within 2km impedance cutoff. This study complements the giant strides by the federal government of Nigeria by providing a blueprint for ensuring proper distribution of these public goods in the spirit of bringing succor to these terrorism ravaged populace. This will ardently at the same time help in boosting agricultural activities thereby lowering food shortage and raising per capita income as espoused by the government.

Keywords: central place theory, GIS, location-allocation, network analysis, urban and regional planning, welfare economics

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Authors: Xuechun Kan, Dongdong Li, Fan Li, Peidang Liu

Abstract:

Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer with a poor prognosis, and radiotherapy is one of the main treatment methods. However, due to the obvious resistance of tumor cells to radiotherapy, high dose of ionizing radiation is required during radiotherapy, which causes serious damage to normal tissues near the tumor. Therefore, how to improve radiotherapy resistance and enhance the specific killing of tumor cells by radiation is a hot issue that needs to be solved in clinic. Recent studies have shown that silver-based nanoparticles have strong radiosensitization, and silver nanoclusters (AgNCs) also provide a broad prospect for tumor targeted radiosensitization therapy due to their ultra-small size, low toxicity or non-toxicity, self-fluorescence and strong photostability. Aptamer 5TR1 is a 25-base oligonucleotide aptamer that can specifically bind to mucin-1 highly expressed on the membrane surface of TNBC 4T1 cells, and can be used as a highly efficient tumor targeting molecule. In this study, AgNCs were synthesized by DNA template based on 5TR1 aptamer (NC-T5-5TR1), and its role as a targeted radiosensitizer in TNBC radiotherapy was investigated. The optimal DNA template was first screened by fluorescence emission spectroscopy, and NC-T5-5TR1 was prepared. NC-T5-5TR1 was characterized by transmission electron microscopy, ultraviolet-visible spectroscopy and dynamic light scattering. The inhibitory effect of NC-T5-5TR1 on cell activity was evaluated using the MTT method. Laser confocal microscopy was employed to observe NC-T5-5TR1 targeting 4T1 cells and verify its self-fluorescence characteristics. The uptake of NC-T5-5TR1 by 4T1 cells was observed by dark-field imaging, and the uptake peak was evaluated by inductively coupled plasma mass spectrometry. The radiation sensitization effect of NC-T5-5TR1 was evaluated through cell cloning and in vivo anti-tumor experiments. Annexin V-FITC/PI double staining flow cytometry was utilized to detect the impact of nanomaterials combined with radiotherapy on apoptosis. The results demonstrated that the particle size of NC-T5-5TR1 is about 2 nm, and the UV-visible absorption spectrum detection verifies the successful construction of NC-T5-5TR1, and it shows good dispersion. NC-T5-5TR1 significantly inhibited the activity of 4T1 cells and effectively targeted and fluoresced within 4T1 cells. The uptake of NC-T5-5TR1 reached its peak at 3 h in the tumor area. Compared with AgNCs without aptamer modification, NC-T5-5TR1 exhibited superior radiation sensitization, and combined radiotherapy significantly inhibited the activity of 4T1 cells and tumor growth in 4T1-bearing mice. The apoptosis level of NC-T5-5TR1 combined with radiation was significantly increased. These findings provide important theoretical and experimental support for NC-T5-5TR1 as a radiation sensitizer for TNBC.

Keywords: 5TR1 aptamer, silver nanoclusters, radio sensitization, triple-negative breast cancer

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