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Commenced in January 2007
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Paper Count: 19801

Search results for: online ad system

3241 Information Communication Technology (ICT) Using Management in Nursing College under the Praboromarajchanok Institute

Authors: Suphaphon Udomluck, Pannathorn Chachvarat

Abstract:

Information Communication Technology (ICT) using management is essential for effective decision making in organization. The Concerns Based Adoption Model (CBAM) was employed as the conceptual framework. The purposes of the study were to assess the situation of Information Communication Technology (ICT) using management in College of Nursing under the Praboromarajchanok Institute. The samples were multi – stage sampling of 10 colleges of nursing that participated include directors, vice directors, head of learning groups, teachers, system administrator and responsible for ICT. The total participants were 280; the instrument used were questionnaires that include 4 parts, general information, Information Communication Technology (ICT) using management, the Stage of concern Questionnaires (SoC), and the Levels of Use (LoU) ICT Questionnaires respectively. Reliability coefficients were tested; alpha coefficients were 0.967for Information Communication Technology (ICT) using management, 0.884 for SoC and 0.945 for LoU. The data were analyzed by frequency, percentage, mean, standard deviation, Pearson Product Moment Correlation and Multiple Regression. They were founded as follows: The high level overall score of Information Communication Technology (ICT) using management and issue were administration, hardware, software, and people. The overall score of the Stage of concern (SoC)ICTis at high level and the overall score of the Levels of Use (LoU) ICTis at moderate. The Information Communication Technology (ICT) using management had the positive relationship with the Stage of concern (SoC)ICTand the Levels of Use (LoU) ICT(p < .01). The results of Multiple Regression revealed that administration hardwear, software and people ware could predict SoC of ICT (18.5%) and LoU of ICT (20.8%).The factors that were significantly influenced by SoCs were people ware. The factors that were significantly influenced by LoU of ICT were administration hardware and people ware.

Keywords: information communication technology (ICT), management, the concerns-based adoption model (CBAM), stage of concern(SoC), the levels of use(LoU)

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3240 Exploring Leadership Adaptability in the Private Healthcare Organizations in the UK in Times of Crises

Authors: Sade Ogundipe

Abstract:

The private healthcare sector in the United Kingdom has experienced unprecedented challenges during times of crisis, necessitating effective leadership adaptability. This qualitative study delves into the dynamic landscape of leadership within the sector, particularly during crises, employing the lenses of complexity theory and institutional theory to unravel the intricate mechanisms at play. Through in-depth interviews with 25 various levels of leaders in the UK private healthcare sector, this research explores how leaders in UK private healthcare organizations navigate complex and often chaotic environments, shedding light on their adaptive strategies and decision-making processes during crises. Complexity theory is used to analyze the complicated, volatile nature of healthcare crises, emphasizing the need for adaptive leadership in such contexts. Institutional theory, on the other hand, provides insights into how external and internal institutional pressures influence leadership behavior. Findings from this study highlight the multifaceted nature of leadership adaptability, emphasizing the significance of leaders' abilities to embrace uncertainty, engage in sensemaking, and leverage the institutional environment to enact meaningful changes. Furthermore, this research sheds light on the challenges and opportunities that leaders face when adapting to crises within the UK private healthcare sector. The study's insights contribute to the growing body of literature on leadership in healthcare, offering practical implications for leaders, policymakers, and stakeholders within the UK private healthcare sector. By employing the dual perspectives of complexity theory and institutional theory, this research provides a holistic understanding of leadership adaptability in the face of crises, offering valuable guidance for enhancing the resilience and effectiveness of healthcare leadership within this vital sector.

Keywords: leadership, adaptability, decision-making, complexity, complexity theory, institutional theory, organizational complexity, complex adaptive system (CAS), crises, healthcare

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3239 Ethanol Chlorobenzene Dosimetr Usage for Measuring Dose of the Intraoperative Linear Electron Accelerator System

Authors: Mojtaba Barzegar, Alireza Shirazi, Saied Rabi Mahdavi

Abstract:

Intraoperative radiation therapy (IORT) is an innovative treatment modality that the delivery of a large single dose of radiation to the tumor bed during the surgery. The radiotherapy success depends on the absorbed dose delivered to the tumor. The achievement better accuracy in patient treatment depends upon the measured dose by standard dosimeter such as ionization chamber, but because of the high density of electric charge/pulse produced by the accelerator in the ionization chamber volume, the standard correction factor for ion recombination Ksat calculated with the classic two-voltage method is overestimated so the use of dose/pulse independent dosimeters such as chemical Fricke and ethanol chlorobenzene (ECB) dosimeters have been suggested. Dose measurement is usually calculated and calibrated in the Zmax. Ksat calculated by comparison of ion chamber response and ECB dosimeter at each applicator degree, size, and dose. The relative output factors for IORT applicators have been calculated and compared with experimentally determined values and the results simulated by Monte Carlo software. The absorbed doses have been calculated and measured with statistical uncertainties less than 0.7% and 2.5% consecutively. The relative differences between calculated and measured OF’s were up to 2.5%, for major OF’s the agreement was better. In these conditions, together with the relative absorbed dose calculations, the OF’s could be considered as an indication that the IORT electron beams have been well simulated. These investigations demonstrate the utility of the full Monte Carlo simulation of accelerator head with ECB dosimeter allow us to obtain detailed information of clinical IORT beams.

Keywords: intra operative radiotherapy, ethanol chlorobenzene, ksat, output factor, monte carlo simulation

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3238 The Role of Community Museum in Ethnic Identity: A Case of Tharu Cultural Museum and Research Center in Chitwan Nepal

Authors: Birendra Mahato, Shiva Narayan Chaudhary

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Tharus are indigenous inhabitants of the Tarai, the narrow strip of flat and fertile land that lies at the foothills of the Himalayas. They have unique rituals, festivals, and music, while their clothes and ornaments are similar to some ethnic groups of India. After the control of malaria in the Terai between 1955 to 1965, (with the help of the U.S. Government, the WHO and the government of Nepal) the rate of in-migration skyrocketed, particularly of Nepal’s hill people, whose culture, along with the use of the Western education system, was gradually adopted by the Tharus. Among the many challenges, the Tharus face is their assimilation into the dominant Nepali culture. .The Tharus are thus under threat of slowly losing their ethnic identity and cultural values. In order to preserve the indigenous Tharu Culture, Tharu Cultural Museum, and Research Center. It is a community based non-governmental and non-profitable museum established in 2005 by Tharu intellectuals, traditional leaders and youths. The main goal of the museum is to preserve Tharu culture through different activities with direct and indirect involvement of community people. It aims to preserve arts, culture, handicrafts, and artifacts related to Indigenous Tharu People. Similarly, the museum displays an exhibition about the Tharu histories, lives, culture, and their indigenous knowledge and skills. The paper aims to demonstrate that community museums can be one of the key hubs for the preservation of culture with the collection and promotion of cultural objects, artifacts, and intangible cultural heritages. The preservation of culture not only has contributed to establishing their ethnic identity but also has contributed to establishing their recognition of their political space in the mainstream politics - the constitution of Nepal has recognized Tharus to provide reservation for the political space.

Keywords: community museum, tharu, , identity, culture

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3237 Agroecology Techniques in Palestine

Authors: Rima Younis

Abstract:

Agro-ecology is considered one of the agricultural approaches that is spreading across the world due to the practical solutions it provides that are in harmony with nature. These solutions target many agricultural problems, food production issues, and climate change. Agriculture and fertile soil in particular, play a vital role when it comes to food security and climate change. The organic substances, which mainly consist of carbon, in the soil contribute to the ecological system through 4 elements: Resistance to soil erosion, conserving water in soil, increasing soil fertility, and improving the biodiversity in it. Any small changes to the carbon storage in soil have a tremendous impact on both agricultural productivity and the greenhouse gas cycle, which is what agro-ecology aims to achieve. The importance of agro-ecology lies here, as it helps increase organic matter/carbon in the soil, on an ongoing basis, 15-20 times higher than nature’s rate in producing organic matter. Agro-ecology is set to increase the production of crops free of chemicals, develop organic matter, and establish carbon in soil, thus being a factor in limiting climate change, not just mitigating or adapting. Under the events of the rapid increase in population and the need to feed humans, agro-ecology stands in the first place as it surpasses the productivity of chemical agriculture per unit area, according to international and local experience. The introduction of agro-ecology to Palestine started 15 years ago, with modest beginnings faced with a lot of criticism and opposition, but is currently experiencing rapid growth among farmers and is becoming accepted among specialists. Even though the number of agro-ecologist farmers is still small, it reflects a state of turnover into a more sustainable, less polluting agriculture that works on renewing life and the elements of nature.

Keywords: toward to solidarity economy, food sovereignty, the introduction of agro-ecology to Palestine, the importance of agro-ecology

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3236 Interpersonal Variation of Salivary Microbiota Using Denaturing Gradient Gel Electrophoresis

Authors: Manjula Weerasekera, Chris Sissons, Lisa Wong, Sally Anderson, Ann Holmes, Richard Cannon

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The aim of this study was to characterize bacterial population and yeasts in saliva by Polymerase chain reaction followed by denaturing gradient gel electrophoresis (PCR-DGGE) and measure yeast levels by culture. PCR-DGGE was performed to identify oral bacteria and yeasts in 24 saliva samples. DNA was extracted and used to generate DNA amplicons of the V2–V3 hypervariable region of the bacterial 16S rDNA gene using PCR. Further universal primers targeting the large subunit rDNA gene (25S-28S) of fungi were used to amplify yeasts present in human saliva. Resulting PCR products were subjected to denaturing gradient gel electrophoresis using Universal mutation detection system. DGGE bands were extracted and sequenced using Sanger method. A potential relationship was evaluated between groups of bacteria identified by cluster analysis of DGGE fingerprints with the yeast levels and with their diversity. Significant interpersonal variation of salivary microbiome was observed. Cluster and principal component analysis of the bacterial DGGE patterns yielded three significant major clusters, and outliers. Seventeen of the 24 (71%) saliva samples were yeast positive going up to 10³ cfu/mL. Predominately, C. albicans, and six other species of yeast were detected. The presence, amount and species of yeast showed no clear relationship to the bacterial clusters. Microbial community in saliva showed a significant variation between individuals. A lack of association between yeasts and the bacterial fingerprints in saliva suggests the significant ecological person-specific independence in highly complex oral biofilm systems under normal oral conditions.

Keywords: bacteria, denaturing gradient gel electrophoresis, oral biofilm, yeasts

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3235 Transcriptome Analysis of Dry and Soaked Tomato (Solanum lycopersicum) Seeds in Response to Fast Neutron Irradiation

Authors: Yujie Zhou, Hee-Seong Byun, Sang-In Bak, Eui-Joon Kil, Kyung Joo Min, Vivek Chavan, Won Kyong Cho, Sukchan Lee, Seung-Woo Hong, Tae-Sun Park

Abstract:

Fast neutron irradiation (FNI) can cause mutations on plant genome but, in the most of cases, these irradiated plants have not shown significant characteristics phenotypically. In this study, we utilized RNA-Seq to generate a high-resolution transcriptome map of the tomato (Solanum lycopersicum) genome effected by FNI. To quantify the different transcription levels in tomato irradiated by FNI, tomato seeds were irradiated by using MC-50 cyclotron (KIRAMS, Korea) for 0, 30 and 90 minutes, respectively. To investigate the effects on the pre-soaking condition, experimental groups were divided into dry and soaked seeds, which were soaked for 8 hours before irradiation. There was no noticeable difference in the percentage germination (PG) among dry seeds, while irradiated soaked seeds have about 10 % lower PG compared to the unirradiated control group. Using whole transcriptome sequencing by HiSeq 2000, we analyzed the differential gene expression in response to different time of FNI in dry and soaked seeds. More than 1.4 million base pair reads were mapped onto the tomato reference genome and the expression pattern differences between irradiated and unirradiated seeds were assessed. In 0, 30 and 90 minutes irradiation, 12,135, 28,495 and 28,675 transcripts were generated, respectively. Gene ontology analysis suggested the different enrichment of transcripts involved in response to different FNI. The present study showed that FNI effects on plant gene expression, which can become a new parameters for evaluating the responses against FNI on plants. In addition, the comparative analysis of differentially expressed genes in D and S seeds by FNI will also give us a chance to deep explore novel candidate genes for FNI, which could be a good model system to understand the mechanisms behind the adaption of plant to space biology research.

Keywords: tomato (solanum lycopersicum), fast neutron irradiation, RNA-sequence, transcriptome expression

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3234 Towards a Biologically Relevant Tumor-on-a-Chip: Multiplex Microfluidic Platform to Study Breast Cancer Drug Response

Authors: Soroosh Torabi, Brad Berron, Ren Xu, Christine Trinkle

Abstract:

Microfluidics integrated with 3D cell culture is a powerful technology to mimic cellular environment, and can be used to study cell activities such as proliferation, migration and response to drugs. This technology has gained more attention in cancer studies over the past years, and many organ-on-a-chip systems have been developed to study cancer cell behaviors in an ex-vivo tumor microenvironment. However, there are still some barriers to adoption which include low throughput, complexity in 3D cell culture integration and limitations on non-optical analysis of cells. In this study, a user-friendly microfluidic multi-well plate was developed to mimic the in vivo tumor microenvironment. The microfluidic platform feeds multiple 3D cell culture sites at the same time which enhances the throughput of the system. The platform uses hydrophobic Cassie-Baxter surfaces created by microchannels to enable convenient loading of hydrogel/cell suspensions into the device, while providing barrier free placement of the hydrogel and cells adjacent to the fluidic path. The microchannels support convective flow and diffusion of nutrients to the cells and a removable lid is used to enable further chemical and physiological analysis on the cells. Different breast cancer cell lines were cultured in the device and then monitored to characterize nutrient delivery to the cells as well as cell invasion and proliferation. In addition, the drug response of breast cancer cell lines cultured in the device was compared to the response in xenograft models to the same drugs to analyze relevance of this platform for use in future drug-response studies.

Keywords: microfluidics, multi-well 3d cell culture, tumor microenvironment, tumor-on-a-chip

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3233 Dynamic Determination of Spare Engine Requirements for Air Fighters Integrating Feedback of Operational Information

Authors: Tae Bo Jeon

Abstract:

Korean air force is undertaking a big project to replace prevailing hundreds of old air fighters such as F-4, F-5, KF-16 etc. The task is to develop and produce domestic fighters equipped with 2 complete-type engines each. A large number of engines, however, will be purchased as products from a foreign engine maker. In addition to the fighters themselves, secure the proper number of spare engines serves a significant role in maintaining combat readiness and effectively managing the national defense budget due to high cost. In this paper, we presented a model dynamically updating spare engine requirements. Currently, the military administration purchases all the fighters, engines, and spare engines at acquisition stage and does not have additional procurement processes during the life cycle, 30-40 years. With the assumption that procurement procedure during the operational stage is established, our model starts from the initial estimate of spare engine requirements based on limited information. The model then performs military missions and repair/maintenance works when necessary. During operation, detailed field information - aircraft repair and test, engine repair, planned maintenance, administration time, transportation pipeline between base, field, and depot etc., - should be considered for actual engine requirements. At the end of each year, the performance measure is recorded and proceeds to next year when it shows higher the threshold set. Otherwise, additional engine(s) will be bought and added to the current system. We repeat the process for the life cycle period and compare the results. The proposed model is seen to generate far better results appropriately adding spare engines thus avoiding possible undesirable situations. Our model may well be applied to future air force military operations.

Keywords: DMSMS, operational availability, METRIC, PRS

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3232 Determination of the CCR5Δ32 Frequency in Emiratis and Tunisians and Screening of the CCR5 Gene for Novel Alleles in Emiratis

Authors: Sara A. Al-Jaberi, Salma Ben-Salem, Meriam Messedi, Fatma Ayadi, Lihadh Al-Gazali, Bassam R. Ali

Abstract:

Background: The chemokine receptor components play crucial roles in the immune system and some of them serve as co-receptors for the HIV virus. Several studies have documented those variants in chemokine receptors are correlated with susceptibility and resistance to infection with HIV virus. For example, mutations in the chemokine receptor 5 gene (CCR5) resulting in loss-of-function (such as the homozygous CCR5Δ32) confer high degree of resistance to HIV infection. Heterozygotes for these variants exhibit slow progression to AIDS. The prevalence of CCR5 polymorphisms varies among ethnic and geographical groups. For example, the CCR5 Δ32 variant is present in 10–15% of north Europeans but is rarely encountered among Africans. This study aims to identify the prevalence of some CCR5 variants in two geographically distant Arab populations (namely Emiratis and Tunisians). Methodology: The prevalence of CCR5 gene variants including CCR5Δ32, FS299, C101X, A29S and C178R has been determined using PCR and direct DNA sequencing. A total of 403 unrelated healthy individuals (253 Emiratis and 150 Tunisians) were genotyped for the CCR5Δ32 variant using PCR amplification and gel electrophoresis. In addition, 200 Emiratis have been screened for other SNPs using Sanger DNA sequencing. Results: Among Emiratis, the allele frequency of the CCR5Δ32 variant has been found to be 0.002. In addition, two variants L55Q and A159 were found at a frequency of 0.002.Moreover, the prevalence of the CCR5Δ32 variant in Tunisians was estimated to be 0.013 which is relatively higher than its frequency in Emiratis but lower than Europeans. Conclusion: We conclude that the allele frequency of the most critical CCR5 polymorphism (Δ32) is extremely low among Emiratis compared to other Arabs and North Europeans. In addition, very low allele frequencies of other CCR5 polymorphisms have been detected among Emiratis.

Keywords: chemokine receptors, CCR5Δ32, CCR5 polymorphisms, Emiratis, Arab populations

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3231 Dynamic Analysis of Functionally Graded Nano Composite Pipe with PZT Layers Subjected to Moving Load

Authors: Morteza Raminnia

Abstract:

In this study, dynamic analysis of functionally graded nano-composite pipe reinforced by single-walled carbon nano-tubes (SWCNTs) with simply supported boundary condition subjected to moving mechanical loads is investigated. The material properties of functionally graded carbon nano tube-reinforced composites (FG-CNTRCs) are assumed to be graded in the thickness direction and are estimated through a micro-mechanical model. In this paper polymeric matrix considered as isotropic material and for the CNTRC, uniform distribution (UD) and three types of FG distribution patterns of SWCNT reinforcements are considered. The system equation of motion is derived by using Hamilton's principle under the assumptions of first order shear deformation theory (FSDT).The thin piezoelectric layers embedded on inner and outer surfaces of FG-CNTRC layer are acted as distributed sensor and actuator to control dynamic characteristics of the FG-CNTRC laminated pipe. The modal analysis technique and Newmark's integration method are used to calculate the displacement and dynamic stress of the pipe subjected to moving loads. The effects of various material distribution and velocity of moving loads on dynamic behavior of the pipe is presented. This present approach is validated by comparing the numerical results with the published numerical results in literature. The results show that the above-mentioned effects play very important role on dynamic behavior of the pipe .This present work shows that some meaningful results that which are interest to scientific and engineering community in the field of FGM nano-structures.

Keywords: nano-composite, functionally garded material, moving load, active control, PZT layers

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3230 Computer-Aided Diagnosis of Eyelid Skin Tumors Using Machine Learning

Authors: Ofira Zloto, Ofir Fogel, Eyal Klang

Abstract:

Purpose: The aim is to develop an automated framework based on machine learning to diagnose malignant eyelid skin tumors. Methods: This study utilized eyelid lesion images from Sheba Medical Center, a large tertiary center in Israel. Before model training, we pre-trained our models on the ISIC 2019 dataset consisting of 25,332 images. The proprietary eyelid dataset was then used for fine-tuning. The dataset contained multiple images per patient, aiming to classify malignant lesions in comparison to benign counterparts. Results: The analyzed dataset consisted of images representing both benign and malignant eyelid lesions. For the benign category, a total of 373 images were sourced. In comparison, the malignant category has 186 images. Based on the accuracy values, the model with 3 epochs and a learning rate of 0.0001 exhibited the best performance, achieving an accuracy of 0.748 with a standard deviation of 0.034. At a sensitivity of 69%, the model has a corresponding specificity of 82%. To further understand the decision-making process of our model, we employed heatmap visualization techniques, specifically Gradient-weighted Class Activation Mapping. Discussion: This study introduces a dependable model-aided diagnostic technology for assessing eyelid skin lesions. The model demonstrated accuracy comparable to human evaluation, effectively determining whether a lesion raises a high suspicion of malignancy or is benign. Such a model has the potential to alleviate the burden on the healthcare system, particularly benefiting rural areas and enhancing the efficiency of clinicians and overall healthcare.

Keywords: machine learning;, eyelid skin tumors;, decision-making process;, heatmap visualization techniques

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3229 The Causes of Governance Inefficiency in the Financial Institutions: An Interdisciplinary Approach to the Theory of Corporate Governance

Authors: Emilia Klepczarek

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The Basel Committee on Banking Supervision and the OECD found problems with the mechanisms of corporate governance as one of the major causes of destabilization of the financial system and the subprime crisis in the years 2007-2010. In response to these allegations, there were formulated a number of recommendations aimed at improving the quality of supervisory standards in financial institutions. They relate mainly to risk management, remuneration policy, the competence of managers and board members and transparency issues. Nevertheless, a review of the empirical research conducted by the author does not allow for an unambiguous confirmation of the positive impact of the postulated standards on the stability of banking entities. There is, therefore, a presumption of the existence of hidden variables determining the effectiveness of the governance mechanisms. According to the author, this involves concepts arising from behavioral economics and economic anthropology, which allow for an explanation of the effectiveness of corporate governance institutions on the basis of the socio-cultural profile of its members. The proposed corporate governance culture theory indicates that the attributes of the members of the organization and organizational culture can determine the different effectiveness level of the governance processes in similar formal corporate governance structures. The aim of the presentation is, firstly, to draw attention to the vast discrepancies existing within the results of research on the effectiveness of the standards of corporate governance in the banking sector. Secondly, the author proposes an explanation of these differences on the basis of governance theory breaking with common paradigms. The corporate governance culture theory is focused on the identity of the individual and the scope of autonomy offered within his or her institution. The coexistence of these two conditions - the adequate behavioral profile and enough freedom to decide - is a prerequisite for the efficient functioning of the institutions of corporate governance, which can contribute to rehabilitating and strengthening the stability of the financial sector.

Keywords: autonomy, corporate governance, efficiency, governance culture

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3228 Optimizing Parallel Computing Systems: A Java-Based Approach to Modeling and Performance Analysis

Authors: Maher Ali Rusho, Sudipta Halder

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The purpose of the study is to develop optimal solutions for models of parallel computing systems using the Java language. During the study, programmes were written for the examined models of parallel computing systems. The result of the parallel sorting code is the output of a sorted array of random numbers. When processing data in parallel, the time spent on processing and the first elements of the list of squared numbers are displayed. When processing requests asynchronously, processing completion messages are displayed for each task with a slight delay. The main results include the development of optimisation methods for algorithms and processes, such as the division of tasks into subtasks, the use of non-blocking algorithms, effective memory management, and load balancing, as well as the construction of diagrams and comparison of these methods by characteristics, including descriptions, implementation examples, and advantages. In addition, various specialised libraries were analysed to improve the performance and scalability of the models. The results of the work performed showed a substantial improvement in response time, bandwidth, and resource efficiency in parallel computing systems. Scalability and load analysis assessments were conducted, demonstrating how the system responds to an increase in data volume or the number of threads. Profiling tools were used to analyse performance in detail and identify bottlenecks in models, which improved the architecture and implementation of parallel computing systems. The obtained results emphasise the importance of choosing the right methods and tools for optimising parallel computing systems, which can substantially improve their performance and efficiency.

Keywords: algorithm optimisation, memory management, load balancing, performance profiling, asynchronous programming.

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3227 Religion and Democracy: Assessing Tolerance in the Diversity of Indonesia

Authors: Harsi Nastiti, Haidar Fikri

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Indonesia has been known for its diversity of cultures, ethnics, religions, and races. This diversity signs as the uniqueness of the country, so tolerance becomes vital point here. As a unitary state, tolerance value is established strongly as the foundation of democracy implementation but recently this tolerance condition facing up some problems after regional election. In this case, religion issue takes a main role for the Indonesian political system which is managed into tolerance breaker especially for local democracy. The election of Jakarta’s Governor 2017 can be said as the momentum for the people to rethink the democracy and tolerance meaning. It begins from one of the governor candidates who makes statement about the majority religion and unfortunately the candidate comes from the minority. The statement emerges into a new social movement based on religiosity. Basically, the social movement which is coordinated by Islamic Defender Front (Front Pembela Islam or FPI) and National Movement to Safeguard the Fatwa-Indonesian Ulama Council (GNPF-MUI) want to demand the justice in the name of blasphemy. The action continuously happens in different names (Action 411, 212, etc.). So, this article analyzes the new phenomenon and how does the impact for the tolerance and democracy life in Indonesia. The method is using qualitative method by review of literature and media content analysis. Results show this phenomenon potentially spreading new conflicts far beyond the goal of the action itself; justice. It makes the conflicts more complex after there are actions such as; Parade Kebhinekaan and Aksi Lilin which contrary reacts to the actions before. These actions and reactions rise up the sensitive issues for Indonesia like religions, Pancasila, unity in diversity, ethnics, and races. At the same time raising skepticism; will it be over after the candidate is getting sentenced or becomes the dangerous latent conflict that will threaten tolerance and democracy in Indonesia.

Keywords: conflict, democracy, religion, tolerance

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3226 Khilafat from Khilafat-e-Rashida: The Rightly Guided the Only Form of Governance to Unite Muslim Countries

Authors: Zoaib Mirza

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Half of the Muslim countries in the world have declared Islam the state religion in their constitutions. Yet, none of these countries have implemented authentic Islamic laws in line with the Quran (Holy Book), practices of Prophet Mohammad (P.B.U.H) called the Sunnah, and his four successors known as the Rightly Guided - Khalifa. Since their independence, these countries have adopted different government systems like Democracy, Dictatorship, Republic, Communism, and Monarchy. Instead of benefiting the people, these government systems have put these countries into political, social, and economic crises. These Islamic countries do not have equal representation and membership in worldwide political forums. Western countries lead these forums. Therefore, it is now imperative for the Muslim leaders of all these countries to collaborate, reset, and implement the original Islamic form of government, which led to the prosperity and success of people, including non-Muslims, 1400 years ago. They should unite as one nation under Khalifat, which means establishing the authority of Allah (SWT) and following the divine commandments related to the social, political, and economic systems. As they have declared Islam in their constitution, they should work together to apply the divine framework of the governance revealed by Allah (SWT) and implemented by Prophet Mohammad (P.B.U.H) and his four successors called Khalifas. This paper provides an overview of the downfall and the end of the Khalifat system by 1924, the ways in which the West caused political, social, and economic crises in the Muslim countries, and finally, a summary of the social, political, and economic systems implemented by the Prophet Mohammad (P.B.U.H) and his successors, Khalifas, called the Rightly Guided – Hazrat Abu Bakr (RA), Hazrat Omar (RA), Hazrat Usman (RA), and Hazrat Ali (RA).

Keywords: khalifat, khilafat-e-Rashida, the rightly guided, colonization, capitalism, neocolonization, government systems

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3225 Place of Radiotherapy in the Treatment of Intracranial Meningiomas: Experience of the Cancer Center Emir Abdelkader of Oran Algeria

Authors: Taleb L., Benarbia M., Boutira F. M., Allam H., Boukerche A.

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Introduction and purpose of the study: Meningiomas are the most common non-glial intracranial tumors in adults, accounting for approximately 30% of all central nervous system tumors. The aim of our study is to determine the epidemiological, clinical, therapeutic, and evolutionary characteristics of a cohort of patients with intracranial meningioma treated with radiotherapy at the Emir Abdelkader Cancer Center in Oran. Material and methods: This is a retrospective study of 44 patients during the period from 2014 to 2020. The overall survival and relapse-free survival curves were calculated using the Kaplan-Meier method. Results and statistical analysis: The median age of the patients was 49 years [21-76 years] with a clear female predominance (sex ratio=2.4). The average diagnostic delay was seven months [2 to 24 months], the circumstances of the discovery of which were dominated by headaches in 54.5% of cases (n=24), visual disturbances in 40.9% (n=18), and motor disorders in 15.9% (n=7). The seat of the tumor was essentially at the level of the base of the skull in 52.3% of patients (n=23), including 29.5% (n=13) at the level of the cavernous sinus, 27.3% (n=12) at the parasagittal level and 20.5% (n=9) at the convexity. The diagnosis was confirmed surgically in 36 patients (81.8%) whose anatomopathological study returned in favor of grades I, II, and III in respectively 40.9%, 29.5%, and 11.4% of the cases. Radiotherapy was indicated postoperatively in 45.5% of patients (n=20), exclusive in 27.3% (n=12) and after tumor recurrence in 27.3% of cases (n=18). The irradiation doses delivered were as follows: 50 Gy (20.5%), 54 Gy (65.9%), and 60 Gy (13.6%). With a median follow-up of 69 months, the probabilities of relapse-free survival and overall survival at three years are 93.2% and 95.4%, respectively, whereas they are 71.2% and 80.7% at five years. Conclusion: Meningiomas are common primary brain tumors. Most often benign but can also progress aggressively. Their treatment is essentially surgical, but radiotherapy retains its place in specific situations, allowing good tumor control and overall survival.

Keywords: diagnosis, meningioma, surgery, radiotherapy, survival

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3224 Time-Dependent Modulation on Depressive Responses and Circadian Rhythms of Corticosterone in Models of Melatonin Deficit

Authors: Jana Tchekalarova, Milena Atanasova, Katerina Georgieva

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Melatonin deficit can cause a disturbance in emotional status and circadian rhythms of the endocrine system in the body. Both pharmacological and alternative approaches are applied for correction of dysfunctions driven by changes in circadian dynamics of many physiological indicators. In the present study, we tested and compare the beneficial effect of agomelatine (40 mg/kg, i.p. for 3 weeks) and endurance training on depressive behavior in two models of melatonin deficit in rat. The role of disturbed circadian rhythms of plasma melatonin and corticosterone secretion in the mechanism of these treatments was also explored. The continuous exercise program attenuated depressive responses associated with disrupted diurnal rhythm of home-cage motor activity, anhedonia in the sucrose preference test, and despair-like behavior in the forced swimming test were attenuated by agomelatine exposed to chronic constant light (CCL) and long-term exercise in pinealectomized rats. Parallel to the observed positive effect on the emotional status, agomelatine restored CCL-induced impairment of circadian patterns of plasma melatonin but not that of corticosterone. In opposite, exercise training diminished total plasma corticosterone levels and corrected its flattened pattern while it was unable to correct melatonin deficit in pinealectomy. These results suggest that the antidepressant-like effect of pharmacological and alternative approach might be mediated via two different mechanism, correction of the disturbed circadian rhythm of melatonin and corticosterone, respectively. Therefore, these treatment approaches might have a potential therapeutic application in different subpopulations of people characterized by a melatonin deficiency. This work was supported by the National Science Fund of Bulgaria (research grant # № DN 03/10; DN# 12/6).

Keywords: agomelatine, exercise training, melatonin deficit, corticosterone

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3223 Reservoir Characterization using Comparative Petrophysical Testing Approach Acquired with Facies Architecture Properties Analysis

Authors: Axel Priambodo, Dwiharso Nugroho

Abstract:

Studies conducted to map the reservoir properties based on facies architecture in which to determine the distribution of the petrophysical properties and calculate hydrocarbon reserves in study interval. Facies Architecture analysis begins with stratigraphic correlation that indicates the area is divided into different system tracts. The analysis of distribution patterns and compiling core analysis with facies architecture model show that there are three estuarine facies appear. Formation evaluation begins with shale volume calculation using Asquith-Krygowski and Volan Triangle Method. Proceed to the calculation of the total and effective porosity using the Bateman-Konen and Volan Triangle Method. After getting the value of the porosity calculation was continued to determine the effective water saturation and non-effective by including parameters of water resistivity and resistivity clay. The results of the research show that the Facies Architecture on the field in divided into three main facies which are Estuarine Channel, Estuarine Sand Bar, and Tidal Flat. The petrophysics analysis are done by comparing different methods also shows that the Volan Triangle Method does not give a better result of the Volume Shale than the Gamma Ray Method, but on the other hand, the Volan Triangle Methode is better on calculating porosity compared to the Bateman-Konen Method. The effective porosity distributions are affected by the distribution of the facies. Estuarine Sand Bar has a low porosity number and Estuarine Channel has a higher number of the porosity. The effective water saturation is controlled by structure where on the closure zone the water saturation is lower than the area beneath it. It caused by the hydrocarbon accumulation on the closure zone.

Keywords: petrophysics, geology, petroleum, reservoir

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3222 New Ethanol Method for Soft Tissue Imaging in Micro-CT

Authors: Matej Patzelt, Jan Dudak, Frantisek Krejci, Jan Zemlicka, Vladimir Musil, Jitka Riedlova, Viktor Sykora, Jana Mrzilkova, Petr Zach

Abstract:

Introduction: Micro-CT is well used for examination of bone structures and teeth. On the other hand visualization of the soft tissues is still limited. The goal of our study was to create a new fixation method for soft tissue imaging in micro-CT. Methodology: We used organs of 18 mice - heart, lungs, kidneys, liver and brain, which we fixated in ethanol after meticulous preparation. We fixated organs in different concentrations of ethanol and for different period of time. We used three types of ethanol concentration - 97%, 50% and ascending ethanol concentration (25%, 50%, 75%, 97% each for 12 hours). Fixated organs were scanned after 72 hours, 168 hours and 336 hours period of fixation. We scanned all specimens in micro-CT MARS (Medipix All Resolution System). Results: Ethanol method provided contrast enhancement in all studied organs in all used types of fixation. Fixation in 97% ethanol provided very fast fixation and the contrast among the tissues was visible already after 72 hours of fixation. Fixation for the period of 168 and 336 hours gave better details, especially in lung tissue, where alveoli were visualized. On the other hand, this type of fixation caused organs to petrify. Fixation in 50% ethanol provided best results in 336 hours fixation, details were visualized better than in 97% ethanol and samples were not as hard as in fixation in 97% ethanol. Best results were obtained in fixation in ascending ethanol concentration. All organs were visualized in great details, best-visualized organ was heart, where trabeculae and valves were visible. In this type of fixation, organs stayed soft for whole time. Conclusion: New ethanol method is a great option for soft tissue fixation as well as the method for enhancing contrast among tissues in organs. The best results were obtained with fixation of the organs in ascending ethanol concentration, the best visualized organ was the heart.

Keywords: x-ray imaging, small animals, ethanol, ex-vivo

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3221 Evaluation of Green Infrastructure with Different Woody Plants Practice and Benefit Using the Stormwater Management-HYDRUS Model

Authors: Bei Zhang, Zhaoxin Zhang, Lidong Zhao

Abstract:

Green infrastructures (GIs) for rainwater management can directly meet the multiple purposes of urban greening and non-point source pollution control. To reveal the overall layout law of GIs dominated by typical woody plants and their impact on urban environmental effects, we constructed a HYDRUS-1D and Stormwater management (SWMM) coupling model to simulate the response of typical root woody plant planting methods on urban hydrological. The results showed that the coupling model had high adaptability to the simulation of urban surface runoff control effect under different woody plant planting methods (NSE ≥0.64 and R² ≥ 0.71). The regulation effect on surface runoff showed that the average runoff reduction rate of GIs increased from 60 % to 71 % with the increase of planting area (5% to 25%) under the design rainfall event of the 2-year recurrence interval. Sophora japonica with tap roots was slightly higher than that of without plants (control) and Malus baccata (M. baccata) with fibrous roots. The comprehensive benefit evaluation system of rainwater utilization technology was constructed by using an analytic hierarchy process. The coupling model was used to evaluate the comprehensive benefits of woody plants with different planting areas in the study area in terms of environment, economy, and society. The comprehensive benefit value of planting 15% M. baccata was the highest, which was the first choice for the planting of woody plants in the study area. This study can provide a scientific basis for the decision-making of green facility layouts of woody plants.

Keywords: green infrastructure, comprehensive benefits, runoff regulation, woody plant layout, coupling model

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3220 Investigation of Heat Transfer Mechanism Inside Shell and Tube Latent Heat Thermal Energy Storage Systems

Authors: Saeid Seddegh, Xiaolin Wang, Alan D. Henderson, Dong Chen, Oliver Oims

Abstract:

The main objective of this research is to study the heat transfer processes and phase change behaviour of a phase change material (PCM) in shell and tube latent heat thermal energy storage (LHTES) systems. The thermal behaviour in a vertical and horizontal shell-and-tube heat energy storage system using a pure thermal conduction model and a combined conduction-convection heat transfer model is compared in this paper. The model is first validated using published experimental data available in literature and then used to study the temperature variation, solid-liquid interface, phase distribution, total melting and solidification time during melting and solidification processes of PCMs. The simulated results show that the combined convection and conduction model can better describe the energy transfer in PCMs during melting process. In contrast, heat transfer by conduction is more significant during the solidification process since the two models show little difference. Also, it was concluded that during the charging process for the horizontal orientation, convective heat transfer has a strong effect on melting of the upper part of the solid PCM and is less significant during melting of the lower half of the solid PCM. However, in the vertical orientation, convective heat transfer is the same active during the entire charging process. In the solidification process, the thermal behavior does not show any difference between horizontal and vertical systems.

Keywords: latent heat thermal energy storage, phase change material, natural convection, melting, shell and tube heat exchanger, melting, solidification

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3219 Manipulating The PAAR Proteins of Acinetobacter Baumannii

Authors: Irene Alevizos, Jessica Lewis, Marina Harper, John Boyce

Abstract:

Acinetobacter baumannii causes a range of severe nosocomial-acquired infections, and many strains are multi-drug resistant. A. baumannii possesses survival mechanisms allowing it to thrive in competitive polymicrobial environments, including a Type VI Secretion System (T6SS) that injects effector proteins into other bacteria to give a competitive advantage. The effects of T6SS firing are broad and depend entirely on the effector that is delivered. Effects can include toxicity against prokaryotic or eukaryotic cells and the acquisition of essential nutrients. The T6SS of some species can deliver ‘specialised effectors’ that are fused directly to T6SS components, such as PAAR proteins. PAAR proteins are predicted to form the piercing tip of the T6SS and are essential for T6SS function. Although no specialised effectors have been identified in A. baumannii, many strains encode multiple PAAR proteins. Analysis of PAAR proteins across the species identified 12 families of PAAR proteins with distinct C-terminal extensions. A. baumannii AB307-0294 encodes two PAAR proteins, one of which has a C-terminal extension. Mutation of one or both of the PAAR-encoding genes in this strain showed that expression of either PAAR protein was sufficient for T6SS function. We employed a heterologous expression approach and determined that PAAR proteins from different A. baumannii strains, as well as the closely related A. baylyi species, could complement the A. baumannii ∆paar mutant and restore T6SS function. Furthermore, we showed that PAAR fusions could be used to deliver artificially cloned protein fragments by generating Histidine- and Streptavidin- tagged PAAR specialised effectors, which restored T6SS activity. This provides evidence that the fusion of protein fragments onto PAAR proteins in A. baumannii is compatible with a functional T6SS. Successful delivery by this mechanism extends the scope of what the T6SS can deliver, including user designed proteins.

Keywords: A. baumannii, effectors, PAAR, T6SS

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3218 Training Undergraduate Engineering Students in Robotics and Automation through Model-Based Design Training: A Case Study at Assumption University of Thailand

Authors: Sajed A. Habib

Abstract:

Problem-based learning (PBL) is a student-centered pedagogy that originated in the medical field and has also been used extensively in other knowledge disciplines with recognized advantages and limitations. PBL has been used in various undergraduate engineering programs with mixed outcomes. The current fourth industrial revolution (digital era or Industry 4.0) has made it essential for many science and engineering students to receive effective training in advanced courses such as industrial automation and robotics. This paper presents a case study at Assumption University of Thailand, where a PBL-like approach was used to teach some aspects of automation and robotics to selected groups of undergraduate engineering students. These students were given some basic level training in automation prior to participating in a subsequent training session in order to solve technical problems with increased complexity. The participating students’ evaluation of the training sessions in terms of learning effectiveness, skills enhancement, and incremental knowledge following the problem-solving session was captured through a follow-up survey consisting of 14 questions and a 5-point scoring system. From the most recent training event, an overall 70% of the respondents indicated that their skill levels were enhanced to a much greater level than they had had before the training, whereas 60.4% of the respondents from the same event indicated that their incremental knowledge following the session was much greater than what they had prior to the training. The instructor-facilitator involved in the training events suggested that this method of learning was more suitable for senior/advanced level students than those at the freshmen level as certain skills to effectively participate in such problem-solving sessions are acquired over a period of time, and not instantly.

Keywords: automation, industry 4.0, model-based design training, problem-based learning

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3217 Energy and Carbon Footprint Analysis of Food Waste Treatment Alternatives for Hong Kong

Authors: Asad Iqbal, Feixiang Zan, Xiaoming Liu, Guang-Hao Chen

Abstract:

Water, food, and energy nexus is a vital subject to achieve sustainable development goals worldwide. Wastewater (WW) and food waste (FW) from municipal sources are primary contributors to their respective wastage sum from a country. Along with the loss of these invaluable natural resources, their treatment systems also consume a lot of abiotic energy and resources input with a perceptible contribution to global warming. Hence, the global paradigm has evolved from simple pollution mitigation to a resource recovery system (RRS). In this study, the prospects of six alternative FW treatment scenarios are quantitatively evaluated for Hong Kong in terms of energy use and greenhouse emissions (GHEs) potential, using life cycle assessment (LCA). Considered scenarios included: aerobic composting, anaerobic digestion (AD), combine AD and composting (ADC), co-disposal, and treatment with wastewater (CoD-WW), incineration, and conventional landfilling as base-case. Results revealed that in terms of GHEs saving, all-new scenarios performed significantly better than conventional landfilling, with ADC scenario as best-case and incineration, AD alone, CoD-WW ranked as second, third, and fourth best respectively. Whereas, composting was the worst-case scenario in terms of energy balance, while incineration ranked best and AD alone, ADC, and CoD-WW ranked as second, third, and fourth best, respectively. However, these results are highly sensitive to boundary settings, e.g., the inclusion of the impact of biogenic carbon emissions and waste collection and transportation, and several other influential parameters. The study provides valuable insights and policy guidelines for the decision-makers locally and a generic modelling template for environmental impact assessment.

Keywords: food waste, resource recovery, greenhouse emissions, energy balance

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3216 Experimental Study and Numerical Simulation of the Reaction and Flow on the Membrane Wall of Entrained Flow Gasifier

Authors: Jianliang Xu, Zhenghua Dai, Zhongjie Shen, Haifeng Liu, Fuchen Wang

Abstract:

In an entrained flow gasifier, the combustible components are converted into the gas phase, and the mineral content is converted into ash. Most of the ash particles or droplets are deposited on the refractory or membrane wall and form a slag layer that flows down to the quenching system. The captured particle reaction process and slag flow and phase transformation play an important role in gasifier performance and safe and stable operation. The reaction characteristic of captured char particles on the molten slag had been studied by applied a high-temperature stage microscope. The gasification process of captured chars with CO2 on the slag surface was observed and recorded, compared to the original char gasification. The particle size evolution, heat transfer process are discussed, and the gasification reaction index of the capture char particle are modeled. Molten slag layer promoted the char reactivity from the analysis of reaction index, Coupled with heat transfer analysis, shrinking particle model (SPM) was applied and modified to predict the gasification time at carbon conversion of 0.9, and results showed an agreement with the experimental data. A comprehensive model with gas-particle-slag flow and reaction models was used to model the different industry gasifier. The carbon conversion information in the spatial space and slag layer surface are investigated. The slag flow characteristic, such as slag velocity, molten slag thickness, slag temperature distribution on the membrane wall and refractory brick are discussed.

Keywords: char, slag, numerical simulation, gasification, wall reaction, membrane wall

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3215 A Decision Making Tool for Selecting the Most Environmental Friendly Wastewater Treatment Plant for Small-Scale Communities

Authors: Mehmet Bulent Topkaya, Mustafa Yildirim

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Wastewater treatment systems are designed and used to minimize adverse impacts of the wastewater on the environment before discharging. Various treatment options for wastewater treatment have been developed, and each of them has different performance characteristics and environmental impacts (e.g. material and land usage, energy consumption, greenhouse gas emission, water and soil emission) during construction, operation or maintenance phases. Assessing the environmental impacts during these phases are essential for the overall evaluation of the treatment systems. In this study, wastewater treatment options, such as vegetated land treatment, constructed wetland, rotating biological contactor, conventional activated sludge treatment, membrane bioreactor, extended aeration and stabilization pond are evaluated. The comparison of the environmental impacts is conducted under the assumption that the effluents will be discharged to sensitive and less sensitive areas respectively. The environmental impacts of each alternative are evaluated by life cycle assessment (LCA) approach. For this purpose, data related to energy usage, land requirement, raw material consumption, and released emissions from the life phases were collected with inventory studies based on field studies and literature. The environmental impacts were assessed by using SimaPro 7.1 LCA software. As the scale of the LCA results is global, an MS-Excel based decision support tool that includes the LCA result is developed in order to meet also the local demands. Using this tool, it is possible to assign weight factors on the LCA results according to local conditions by using Analytical Hierarchy Process and finally the most environmentally appropriate treatment option can be selected.

Keywords: analytical hierarchy process, decision support system, life cycle assessment, wastewater treatment

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3214 Modelling the Effect of Biomass Appropriation for Human Use on Global Biodiversity

Authors: Karina Reiter, Stefan Dullinger, Christoph Plutzar, Dietmar Moser

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Due to population growth and changing patterns of production and consumption, the demand for natural resources and, as a result, the pressure on Earth’s ecosystems are growing. Biodiversity mapping can be a useful tool for assessing species endangerment or detecting hotspots of extinction risks. This paper explores the benefits of using the change in trophic energy flows as a consequence of the human alteration of the biosphere in biodiversity mapping. To this end, multiple linear regression models were developed to explain species richness in areas where there is no human influence (i.e. wilderness) for three taxonomic groups (birds, mammals, amphibians). The models were then applied to predict (I) potential global species richness using potential natural vegetation (NPPpot) and (II) global ‘actual’ species richness after biomass appropriation using NPP remaining in ecosystems after harvest (NPPeco). By calculating the difference between predicted potential and predicted actual species numbers, maps of estimated species richness loss were generated. Results show that biomass appropriation for human use can indeed be linked to biodiversity loss. Areas for which the models predicted high species loss coincide with areas where species endangerment and extinctions are recorded to be particularly high by the International Union for Conservation of Nature and Natural Resources (IUCN). Furthermore, the analysis revealed that while the species distribution maps of the IUCN Red List of Threatened Species used for this research can determine hotspots of biodiversity loss in large parts of the world, the classification system for threatened and extinct species needs to be revised to better reflect local risks of extinction.

Keywords: biodiversity loss, biomass harvest, human appropriation of net primary production, species richness

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3213 Critical Review of the Democracy in Pakistan in Light of Dr. Israr Ahmed and Western Philosophers

Authors: Zoaib Mirza

Abstract:

Pakistan is an Islamic country that got its partition from India in 1947 so that the people could practice the religion of Islam. The ideology of Pakistan was based on the notion that sovereignty only belonged to God Almighty (in Arabic, God means “Allah”), and Muslims will live in accordance with Islam principles. The Quran (Holy Book) and Sunnah (authentic practices of Prophet Mohammad, Peace Be Upon Him, that explains the application of the Quran) are foundations of the Islamic principles. It has been over 75 years, but unfortunately, Pakistan, due to its own political, social, and economic mistakes, is responsible for not being able to become a true Islamic nation to justify its partition from India. The rationale for writing this paper is to analyze the factors that led to changes in the democratic movements impacting the country's political, social, and economic growth. The methodology to examine the historical and political context of Pakistan’s history is by referencing the scholarly work of Israr Ahmed, a Pakistani Islamic theologian, philosopher, and Islamic scholar. While from a Western perspective, Karl Marx, Mar Weber, Hannah Arendt, Sheldon Wolin, Paulo Freire, and Jacques Ranciere's philosophies specific to totalitarianism, politics, military rule, religion, capitalism, and superpower are used as the framework to analyze Pakistan’s democracy. The study's findings conclude that Pakistan's democracy is unstable and has been impacted by military and civilian governance, which led to political, social, and economic downfall. To improve the current situation, the citizens of Pakistan have to realize that the success of a nation is only dependent on the level of consciousness of the leader and not the political system. Therefore, it is the responsibility of every citizen to be conscious of how they select their leader and take responsibility for the current situation in Pakistan.

Keywords: Pakistan, Islam, democracy, totalitarianism, military, religion, capitalism

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3212 “MaxSALIVA-II” Advancing a Nano-Sized Dual-Drug Delivery System for Salivary Gland Radioprotection, Regeneration and Repair in a Head and Neck Cancer Pre-Clinical Murine Model

Authors: Ziyad S. Haidar

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Background: Saliva plays a major role in maintaining oral, dental, and general health and well-being; where it normally bathes the oral cavity acting as a clearing agent. This becomes more apparent when the amount and quality of saliva are significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the 5th most common malignancy worldwide, during which the salivary glands are included within the radiation field/zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely as they become malnourished and experience a significant decrease in their QoL. Accordingly, the formulation of a radio-protection/-prevention modality and development of an alternative Rx to restore damaged salivary gland tissue is eagerly awaited and highly desirable. Objectives: Assess the pre-clinical radio-protective effect and reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs, followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: cancer, head and neck, oncology, drug development, drug delivery systems, nanotechnology, nanoncology

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