Search results for: stable platform

Authors: Thirupathi Thippani, Kothandaraman Ramanujam

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Current research on energy storage has been paid to metal-air batteries, because of attractive alternate energy source for the future. Metal – air batteries have the probability to significantly increase the power density, decrease the cost of energy storage and also used for a long time due to its high energy density, low-level pollution, light weight. The performance of these batteries mostly restricted by the slow kinetics of the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) on cathode during battery discharge and charge. The ORR and OER are conventionally carried out with precious metals (such as Pt) and metal oxides (such as RuO₂ and IrO₂) as catalysts separately. However, these metal-based catalysts are regularly undergoing some difficulties, including high cost, low selectivity, poor stability and unfavorable to environmental effects. So, in order to develop the active, stable, corrosion resistance and inexpensive bi-functional catalyst material is mandatory for the commercialization of zinc-air rechargeable battery technology. We have attempted and synthesized non-precious metal (NPM) catalysts comprising cobalt and N-doped multiwalled carbon nanotubes (N-MWCNTs-Co) were synthesized by the solid-state pyrolysis (SSP) of melamine with Co₃O₄. N-MWCNTs-Co acts as an excellent electrocatalyst for both the oxygen reduction reaction (ORR) and the oxygen evolution reaction (OER), and hence can be used in secondary metal-air batteries and in unitized regenerative fuel cells. It is important to study the OER and ORR at high concentrations of KOH as most of the metal-air batteries employ KOH concentrations > 4M. In the first 16 cycles of the zinc-air battery while using N-MWCNTs-Co, 20 wt.% Pt/C or 20 wt.% IrO₂/C as air electrodes. In the ORR regime (the discharge profile of the zinc-air battery), the cell voltage exhibited by N-MWCNTs-Co was 44 and 83 mV higher (based on 5th cycle) in comparison to of 20 wt.% Pt/C and 20 wt.% IrO₂/C respectively. To demonstrate this promise, a zinc-air battery was assembled and tested at a current density of 0.5 Ag⁻¹ for charge-discharge 100 cycles.

Keywords: oxygen reduction reaction (ORR), oxygen evolution reaction(OER), non-platinum, zinc air battery

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Authors: Shahroz Khan, Erkan Gunpinar, Kemal Mart

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Recently parametric design techniques became a vital concept in the field of Computer Aided Design (CAD), which helps to provide sophisticated platform to the designer in order to automate the design process in efficient time. In these techniques, design process starts by parameterizing the important features of design models (typically the key dimensions), with the implementation of design constraints. The design constraints help to retain the overall shape of the model while modifying its parameters. However, the process of initializing an appropriate number of design parameters and constraints is the crucial part of parametric design techniques, especially for complex surface models such as yacht hull. This paper introduces a method to create complex surface models in favor of parametric design techniques, a method to define the right number of parameters and respective design constraints, and a system to implement design parameters in contract to design constraints schema. For this, in our proposed approach the design process starts by dividing the yacht hull into three sections. Each section consists of different shape lines, which form the overall shape of yacht hull. The shape lines are created using Cubic Bezier Curves, which allow larger design flexibility. Design parameters and constraints are defined on the shape lines in 3D design space to facilitate the designers for better and individual handling of parameters. Afterwards, shape modifiers are developed, which allow the modification of each parameter while satisfying the respective set of criteria and design constraints. Such as, geometric continuities should be maintained between the shape lines of the three sections, fairness of the hull surfaces should be preserved after modification and while design modification, effect of a single parameter should be negligible on other parameters. The constraints are defined individually on shape lines of each section and mutually between the shape lines of two connecting sections. In order to validate and visualize design results of our shape modifiers, a real time graphic interface is created.

Keywords: design parameter, design constraints, shape modifies, yacht hull

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Authors: Lynette Sheridan Burns, Benjamin J. Matthews

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The context of post-industrial journalism is one in which the material circumstances of mechanical publication have been displaced by digital technologies, increasing the distance between the orthodoxy of the newsroom and the culture of journalistic writing. Content is, with growing frequency, created for delivery via the internet, publication on web-based ‘platforms’ and consumption on screen media. In this environment, the question is not ‘who is a journalist?’ but ‘what is journalism?’ today. The changes bring into sharp relief new distinctions between journalistic work and journalistic labor, providing a key insight into the current transition between the industrial journalism of the 20^th century, and the post-industrial journalism of the present. In the 20^th century, the work of journalists and journalistic labor went hand-in-hand as most journalists were employees of news organizations, whilst in the 21^st century evidence of a decoupling of ‘acts of journalism’ (work) and journalistic employment (labor) is beginning to appear. This 'decoupling' of the work and labor that underpins journalism practice is far reaching in its implications, not least for institutional structures. Under these conditions we are witnessing the emergence of expanded ‘entrepreneurial’ journalism, based on smaller, more independent and agile - if less stable - enterprise constructs that are a feature of creative industries. Entrepreneurial journalism is realized in a range of organizational forms from social enterprise, through to profit driven start-ups and hybrids of the two. In all instances, however, the primary motif of the organization is an ideological definition of journalism. An example is the Scoop Foundation for Public Interest Journalism in New Zealand, which owns and operates Scoop Publishing Limited, a not for profit company and social enterprise that publishes an independent news site that claims to have over 500,000 monthly users. Our paper demonstrates that this journalistic work meets the ideological definition of journalism; conducted within the creative industries using an innovative organizational structure that offers a new, viable post-industrial future for journalism.

Keywords: creative industries, digital communication, journalism, post industrial

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Authors: Rona Hanani Simamora, Bahagia Loebis, M. Surya Husada

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Background: The exact cause of schizophrenia is not known, although several etiology theories have been proposed for the disease, including immune dysfunction or autoimmune mechanisms. Cytokines including Tnf-α has an important role in the pathophysiology of schizophrenia and the effects of pharmacological treatment with antipsychotics. Nicotine is widespread effects on the brain, immune system and cytokine levels. Smoking among schizophrenic patients could play a role in the altered cytokine profiles of schizophrenia such as Tnf-α. Aims: To determine differences of serum Tnf-α levels between schizophrenic patients with smoking in male and healthy control. Methods: This study was a comparative analytic study, divided into two groups: 1) group of male schizophrenic patients with smoking (n1=30) with inclusion criteria were patients who have been diagnosed schizophrenic based PPDGJ-III, 20-60 years old, male, smoking, chronic schizophrenic patients in the stable phase and willing to participate this study. Exclusion criteria were having other mental disorders and comorbidity with other medical illnesses. 2) healthy control group (n2=30) with inclusion criteria were 20-60 years old, male, smoking, willing to participate this study. Exclusion criteria were having mental disorder, a family history of psychiatric disorders, the other medical illnesses, a history of alcohol and other substances abuse (except caffeine and nicotine). Serum Tnf-α were analyzed using the Quantikine HS Human Tnf –α Immunoassay. Results: Serum Tnf-α level measure in patient schizophrenia male with smoking and compared with the healthy control subjects. Tnf-α levels were significantly higher in patients schizophrenic male with smoking (25,79±27,96) to healthy control subjects (2,74±2,19), by using the Mann Whitney U test showed a statistically significant difference was observed for serum Tnf-α level (p < 0,001). Conclusions: Schizophrenia is a highly heterogeneous disorder, and this study shows an increase Tnf-α as pro-inflammation cytokines in schizophrenics. These results suggest an immune abnormalities may be involved in the etiology and pathophysiology of schizophrenia.

Keywords: male, schizophrenic, smoking, Tnf Alpha

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Authors: Dylan Yanano Mangani, Theodore Nkadimeng Mahosi

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Soon after independence on 18th April 1980, Zimbabwe’s foreign policy was shaped by the realities on the ground, which saw the country managing a sound relationship with both the Capitalist West and the Communist Eastern blocs. The post-independence foreign policy was therefore premised on security concerns illuminated by the Cold War era. This was one the reasons President Robert Mugabe adopted a policy of reconciliation and this earned his government recognition on the international platform. However, in Southern Africa apartheid South Africa was still the vanguard of capitalism and oppression such that she posed a serious threat to the newly born Zimbabwean nation which necessitated that Zimbabwe position herself both in the region and the continent to counter potential internal stability from within. Irrespective of how the international community viewed the country’s foreign policy Zimbabwe has continued to influence regional, continental and world geo-politics, especially on behalf of the developing nations. This raises a question why as a result of its foreign policy the country is now regarded a pariah state, especially some Western countries which used to applaud its political economic policies immediately after independence. Therefore, this study argues that the political economy of Zimbabwe had a far-reaching bearing on its foreign policy. For this reason, the problem necessitates the investigation of Zimbabwe’s foreign policy perspectives in Southern Africa since the turn of the 1990s. Two main theories which are Realism, Afro-centrism inform the study as an attempt to understand Zimbabwe’s foreign policy paradigm shift and perhaps provide answers to the objectives raised. The research therefore employs a qualitative approach where the conceptual nature of the study into the foreign policy of Zimbabwe is largely desktop research. However, the nature of the study will also require that oral interviews are conducted to substantiate some of the arguments advanced.

Keywords: cold war set up, foreign policy, look east policy, pan-africanism, post 2000 period, Southern Africa, Zimbabwe

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Authors: Dieudonne Mevono Mvogo

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The Intergovernmental Platform on Biodiversity and Ecosystem Services (IPBES)-Intergovernmental Panel on Climate Change (IPCC) co-sponsored workshop report suggests that climate change and biodiversity loss are two of the most pressing issues of the Anthropocene. Research establishes the interconnection between climate change and biodiversity. On the one hand, the impact of climate change on biodiversity loss – 14 % over the past century – is projected to surpass other threats – land and sea use 34 % and direct exploitation of species 23 % – during the 21st century. Response measures to climate change also affect biodiversity negatively or positively. On the other hand, actions to halt or reverse biodiversity loss can enhance land and ocean capacity for carbon sequestration. These actions can also promote adaptation by ensuring adaptive capacity. This systemic interaction between climate change and biodiversity affects the human quality of life. The United Nations Secretariat's report entitled 'Gaps in international environmental law and environment-related instruments: towards a global pact for the environment,' released in 2018, states that cooperation and mutual support among agreements dealing with climate change, the protection of the marine environment, freshwater resources and hazardous waste are indispensable for the effective implementation of the Convention on the Biological Diversity (CBD). Since biodiversity is being lost at an alarming rate, this study aims to evaluate the cooperative framework for the coherence and coordination between climate change and biodiversity regimes to provide co-benefits for climate and biodiversity crises. It questions the potential improvement regarding integrating ecosystem-based approaches and nature-based solutions – promoted by the CBD – into the United Nations Framework Convention on Climate Change (UNFCCC).

Keywords: rio conventions, climate change, biodiversity, cooperative framework, ecosystem-based approaches, nature-based solutions

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Authors: Sarchil H. Qader, Andrew Harfoot, Mathias Kuepie, Sabrina Juran, Attila Lazar, Andrew J. Tatem

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The need for high-quality, reliable, and timely population data, including demographic information, to support the achievement of the sustainable development goals (SDGs) in all countries was recognized by the United Nations' 2030 Agenda for sustainable development. However, many low and middle-income countries lack reliable and recent census data. To achieve reliable and accurate census and survey outputs, up-to-date census enumeration areas and digital national sampling frames are critical. Census enumeration areas (EAs) are the smallest geographic units for collection, disseminating, and analyzing census data and are often used as a national sampling frame to serve various socio-economic surveys. Even for countries that are wealthy and stable, creating and updating EAs is a difficult yet crucial step in preparing for a national census. Such a process is commonly done manually, either by digitizing small geographic units on high-resolution satellite imagery or walking the boundaries of units, both of which are extremely expensive. We have developed a user-friendly tool that could be employed to generate draft EA boundaries automatically. The tool is based on high-resolution gridded population and settlement datasets, GPS household locations, building footprints and uses publicly available natural, man-made and administrative boundaries. Initial outputs were produced in Burkina Faso, Paraguay, Somalia, Togo, Niger, Guinea, and Zimbabwe. The results indicate that the EAs are in line with international standards, including boundaries that are easily identifiable and follow ground features, have no overlaps, are compact and free of pockets and disjoints, and the boundaries are nested within administrative boundaries.

Keywords: enumeration areas, national sampling frame, gridded population data, preEA tool

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Authors: Shang-Hsin Ou, Yang-Chun Lin, Ke-Hao Cheng

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The year 2021 marked a historic drought in Taiwan, posing unprecedented challenges due to record-low rainfall and inadequate reservoir storage. The central region experienced water scarcity, leading to the implementation of "Groundwater Utilization at Construction Sites" for drought-resilient livelihood water supply. This study focuses on the establishment process of temporary groundwater treatment plants at construction sites in Taichung City, serving as a reference for future emergency response and the utilization of construction site groundwater. To identify suitable sites for groundwater reuse projects, site selection operations were carried out based on relevant water quality regulations and assessment principles. Subsequently, the planning and design of temporary water treatment plants were conducted, considering the water quality, quantity, and on-site conditions of groundwater wells associated with construction projects. The study consolidates the major water treatment facilities at each site and addresses encountered challenges during the establishment process. Practical insights gained from operating temporary groundwater treatment plants are presented, including improvements related to stable water quality, water quantity, equipment operation, and hydraulic control. In light of possible future droughts, this study provides an outlook and recommendations to expedite and improve the setup of groundwater treatment plants at construction sites. This includes considering on-site water abstraction, treatment, and distribution conditions. The study's results aim to offer practical guidelines for effectively establishing and managing such treatment plants, while offering experiences and recommendations for other regions facing similar emergencies, water shortages, and drought situations. These endeavors contribute to ensuring sustainable water supply for drought-resilient livelihoods and maintaining societal stability.

Keywords: drought resilience, groundwater treatment, construction site, water supply

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Authors: B. Hammouti, H. Oudda, A. Benabdellah, A. Benayada, A. Aouniti

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Corrosion behaviour of carbon steel was studied in various concentrated HClO4 solutions. To explain the acid attack in relation of H+ activity, new sensor was realised: two carbon paste electrodes (CPE) were constructed by incorporating ferrocene (Fc) and orthoquinone into the carbon paste matrix and crossed by weak current to stabilize potential difference. The potentiometric method at imposed weak current between these two electrodes permits the in situ determination of both concentration and acidity level of various concentrated HClO4 solutions. The different factors affecting the potential at imposed current as current intensity, temperature and H+ ion concentration are studied. The potentials measured between ferrocene and chloranil electrodes are directly linked to the acid concentration. The acidity Ri(H) function defined represents the determination of the H+ activity and constitutes the extend of pH is concentrated acid solutions. Ri(H) has been determined and compared to Strehlow Ro(H), Janata HGF and Hammett Ho functions. The collected data permit to give a scale of strength of mineral concentrated acids at a given concentration. Ri(H) is numerically equal to the thermodynamic Ro(H), but deviated from Hammett functions based on indicator determination. The CPE electrode with inserted ferrocene in presence of ferricinium (Fc+) ion in concentrated HClO4 at various concentrations is realized without junction potential and may plays the role of a practical reference electrode (FRE) in concentrated acids. Fc+ was easily prepared in biphasic medium HClO4-acid by the quantitative oxidation of ferrocene by the ortho-chloranil (oQ). Potential of FRE is stable with time. The variation of equilibrium potential of the interface Fc/ Fc+ at various concentrations of Fc+ (10-4 - 2 10-2 M) obeyed to the Nernst equation with a slope 0.059 Volt per decade. Corrosion rates obtained by weight loss and electrochemical techniques were then easily linked to acidity level.

Keywords: ferrocene, strehlow, concentrated acid, corrosion, Generalised pH, sensor carbon paste electrode

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Authors: Kevin A. Droguett, Edwin G. Pérez, Denis Fuentealba, Margarita E. Aliaga, Angélica M. Fierro

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Supramolecular chemistry is a field of growing interest. Moreover, studying the formation of host-guest complexes between macrocycles and dyes is highly attractive due to their potential applications. Examples of the above are drug delivery, catalytic process, and sensing, among others. There are different dyes of interest in the literature; one example is the quinolinone derivatives. Those molecules have good optical properties and chemical and thermal stability, making them suitable for developing fluorescent probes. Secondly, several macrocycles can be seen in the literature. One example is the cucurbiturils. This water-soluble macromolecule family has a hydrophobic cavity and two identical carbonyl portals. Additionally, the thermodynamic analysis of those supramolecular systems could help understand the affinity between the host and guest, their interaction, and the main stabilization energy of the complex. In this work, two 7-(diethylamino) quinoline-2 (1H)-one derivative (QD1-2) and their interaction with cucurbit[7]uril (CB[7]) were studied from an experimental and in-silico point of view. For the experimental section, the complexes showed a 1:1 stoichiometry by HRMS-ESI and isothermal titration calorimetry (ITC). The inclusion of the derivatives on the macrocycle lends to an upward shift in the fluorescence intensity, and the pKa value of QD1-2 exhibits almost no variation after the formation of the complex. The thermodynamics of the inclusion complexes was investigated using ITC; the results demonstrate a non-classical hydrophobic effect with a minimum contribution from the entropy term and a constant binding on the order of 106 for both ligands. Additionally, dynamic molecular studies were carried out during 300 ns in an explicit solvent at NTP conditions. Our finding shows that the complex remains stable during the simulation (RMSD ~1 Å), and hydrogen bonds contribute to the stabilization of the systems. Finally, thermodynamic parameters from MMPBSA calculations were obtained to generate new computational insights to compare with experimental results.

Keywords: host-guest complexes, molecular dynamics, quinolin-2(1H)-one derivatives dyes, thermodynamics

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Authors: Okan Cakir, Okan Tatli

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Acute motor and sensory axonal neuropathy (AMSAN) syndrome usually occurs following a postviral infection in two to four weeks and is a polyneuropathy characterized by axonal and sensorial degeneration as a rare variant of Gullian-Barre syndrome. In our case, we wanted to mention that a rare case of AMSAN Syndrome due to prior surgery. A 61-year-old male case admitted to emergency department with complaints of weakness in feet, numbness and incapability to walk. In his history, it was learned that endovascular aneurysm repair (EVAR) had applied for abdominal aort aneurysm two weeks ago before admission, his complaints had been for a couple of days increasingly and bilaterally, and there had been no infection disease history for four weeks. In physical examination, general status was good, vital signs were stable, and there was a mild paresis in dorsal flexion of feet in bilaterally lower extremities. No nuchal rigidity was determined. Other system examinations were normal. Urea:52 mg/dL (normal range: 15-44 mg/dL), creatinine: 1,05 mg/dL (normal range: 0,81-1,4 mg/dL), potassium: 3,68 mmol/L (normal range: 3,5-5,5 mmol/L), glycaemia: 142 mg/dL, calcium: 9,71 mg/dL (normal range: 8,5-10,5 mg/dL), erythrocyte sedimentation rate (ESR): 74 mm/h (normal range: 0-15 mm/h) were determined in biochemical tests. The case was consulted to neurology department and hospitalized. In performing electromyography, it was reported as a bilateral significant axonal degeneration with sensory-motor polyneuropathy. Normal ranges of glycaemia and protein levels were detected in lumbal punction. Viral markers and bucella, toxoplasma, and rubella markers were in normal range. Intravenous immunoglobulin (IVIG) was applied as a treatment, physical treatment programme was planned and the case discharged from neurology department. In our case, we mentioned that it should be considered polyneuropathy as an alternative diagnosis in cases admitting symptoms like weakness and numbness had a history of prior surgery.

Keywords: AMSAN Syndrome, emergency department, prior surgery, weakness

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Authors: Tingyu Zhang

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The horizontal ecological compensation (HEC) mechanism is the key to stimulating the active participation of the whole basin in ecological protection. In this paper, we construct an evolutionary model for HEC in the Yangtze River Economic Belt (YREB) basin with the introduction of the central government constraint and incentive mechanism (CGCIM) and explore the conditions for the realization of a (Protection and compensation) strategy that meets the social expectations. Further, the water quality-water quantity model is utilized to measure the HEC amount with the characteristic factual data of the YREB in 2020-2022. The results show that the stability of the evolutionary game model of upstream and downstream governments in the YREB is closely related to the CGCIM. If (Protection Compensation) is to be realized as the only evolutionary stable strategy of the evolutionary game system composed of upstream and downstream governments, it is necessary for the CGCIM to satisfy that the sum of the incentives for the protection side and its unilateral or bilateral constraints is greater than twice the input cost of the active strategy, and the sum of the incentives for the compensation side and its unilateral or bilateral constraints is greater than the amount of ecological compensation that needs to be paid by it when it adopts the active strategy. At this point, the total amount of HEC that the downstream government should give to the upstream government of the YREB is 2856.7 million yuan in 2020, 5782.1 million yuan in 2021, and 23166.7 million yuan in 2022. The results of the study can provide a reference for promoting the improvement and refinement of the HEC mechanism in the YREB.

Keywords: horizontal ecological compensation, Yangtze river economic belt, evolutionary game analysis, water quality and quantity model research on territorial ecological restoration in Mianzhu city, Sichuan, under the dual evaluation framework

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Authors: Raif Parlakkaya, Mustafa Nihat Demirci, Mehmet Nuri Salur

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Environmental pollution has detrimental effects on the quality of our life and its scope has reached such an extent that measures are being taken both at the national and international levels to reduce, prevent and mitigate its impact on social, economic and political spheres. Therefore, awareness of environmental problems has been increasing among stakeholders and accordingly among companies. It is seen that corporate reporting is expanding beyond environmental performance. Primary purpose of publishing an environmental report is to provide specific audiences with useful, meaningful information. This paper is intended to analyze the extent and qualification of environmental disclosures of Turkish publicly quoted firms and see how it varies from one sector to another. The data for the study were collected from annual activity reports of companies, listed on the corporate governance index (BIST-XKURY) of Istanbul Stock Exchange. Content analysis was the research methodology used to measure the extent of environmental disclosure. Accordingly, 2015 annual activity reports of companies that carry out business in some particular fields were acquired from Capital Market Board, websites of Public Disclosure Platform and companies’ own websites. These reports were categorized into five main aspects: Environmental policies, environmental management systems, environmental protection and conservation activities, environmental awareness and information on environmental lawsuits. Subsequently, each component was divided into several variables related to what each firm is supposed to disclose about environmental information. In this context, the nature and scope of the information disclosed on each item were assessed according to five different ways (N.I: No Information; G.E.: General Explanations; Q.E.: Qualitative Detailed Explanations; N.E.: Quantitative (numerical) Detailed Explanations; Q.&N.E.: Both Qualitative and Quantitative Explanations).

Keywords: environmental accounting, disclosure, corporate governance, content analysis

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Authors: Meenu Joshi, Natalie Naidoo, Farzeen Kader

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Identification of body fluids is an essential step in forensic investigation to aid in crime reconstruction. Tissue-specific differentially methylated regions (tDMRs) of the human genome can be targeted to be used as biomarkers to differentiate between body fluids. The present study was undertaken to establish the methylation status of potential tDMRs in blood, semen, saliva, and vaginal fluid by using methylation-specific PCR (MSP) and bisulfite sequencing (BS). The methylation statuses of 3 potential tDMRS in genes ZNF282, PTPRS, and HPCAL1 were analysed in 10 samples of each body fluid. With MSP analysis, the ZNF282, and PTPRS1 tDMR displayed semen-specific hypomethylation while HPCAL1 tDMR showed saliva-specific hypomethylation. With quantitative analysis by BS, the ZNF282 tDMR showed statistically significant difference in overall methylation between semen and all other body fluids as well as at individual CpG sites (p < 0.05). To evaluate the effect of environmental conditions on the stability of methylation profiles of the ZNF282 tDMR, five samples of each body fluid were subjected to five different forensic simulated conditions (dry at room temperature, wet in an exsiccator, outside on the ground, sprayed with alcohol, and sprayed with bleach) for 50 days. Vaginal fluid showed highest DNA recovery under all conditions while semen had least DNA quantity. Under outside on the ground condition, all body fluids except semen showed a decrease in methylation level; however, a significant decrease in methylation level was observed for saliva. A statistical significant difference was observed for saliva and semen (p < 0.05) for outside on the ground condition. No differences in methylation level were observed for the ZNF282 tDMR under all conditions for vaginal fluid samples. Thus, in the present study ZNF282 tDMR has been identified as a novel and stable semen-specific hypomethylation marker.

Keywords: body fluids, bisulphite sequencing, forensics, tDMRs, MSP

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Authors: Abdul Nasir Zamir

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After the downfall of Ottoman Caliphate, it scattered into different small Muslim states. Muslim leaders, intellectuals, revivalists as well as modernists started trying to boost up their nation. Some Muslims are also trying to establish the caliphate. Every Muslim country has its own political system, i.e., kingship, dictatorship or democracy, etc. But these are not in their original forms as the historian or political science discussed in their studies. The laws and their practice are mixed, i.e., others with Islamic laws, e.g., Saudi Arabia (K.S.A) and the Islamic Republic of Pakistan, etc. There is great conflict among the revivalist Muslim parties (groups) and governments about political systems. The question is that the subject matter is Sharia or political system? Leaders of Modern Muslim states are alleged as disbelievers due to neglecting the revelation in their laws and decisions. There are two types of laws; Islamic laws and management laws. The conflict is that the non-Islamic laws are in practice in Muslim states. Non-Islamic laws can be gradually changed with Islamic laws with a legal and peaceful process according to the practice of former Muslim leaders and scholars. The bloodshed of Muslims is not allowed in any case. Weak Muslim state is a blessing than nothing. The political system after Muhammad and guided caliphs is considered as kingship. But during this period Muslims not only developed in science and technology but conquered many territories also. If the original aim is in practice, then the Modern Muslim states can be stabled with different political systems. Modern Muslim states are the hope of survival, stability, and development of Muslim Ummah. Islam does not allow arm clash with Muslim army or Muslim civilians. The caliphate is based on believing in one Allah Almighty and good deeds according to Quran and Sunnah. As faith became weak and good deeds became less from its standard level, caliphate automatically became weak and even ended. The last weak caliphate was Ottoman Caliphate which was a hope of all the Muslims of the world. There is no caliphate or caliph present in the world. But every Muslim country or state is like an Amarat (a part of caliphate or small and alternate form of the caliphate) of Muslims. It is the duty of all Muslims to stable these modern Muslim states with tolerance.

Keywords: caliphate, conflict resolution, modern Muslim state, political conflicts, political systems, tolerance

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Authors: Shanmugasundaram Selvadurai, Amal Chandran

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Small satellites have become an alternative low-cost solution for several missions to accomplish specific missions such as Earth imaging, Technology demonstration, Education, and other commercial purposes. Small satellite missions focusing on Infrared imaging applications require lower temperature for scientific instruments and such low temperature can be achieved only using external cryocoolers but the disadvantage is that they generate a large amount of waste heat. Existing passive thermal control techniques are not capable to handle such large thermal loads and hence one of the traditional active Thermal Control System (TCS) is studied for a small satellite configuration. This work aims to downscale the existing Mechanically Pumped Fluid Loop (MPFL) TCS to a 27U CubeSat platform for an imaginary scientific instrument. The temperature-sensitive detector in the instrument considered to be maintained between 130K and 150K to reduce dark current noise and increase the data quality. A Single-Phase fluid based MPFL is chosen for this system-level study and this TCS consists of a microfluid pump, a micro-cryocooler, a fluid accumulator, external heaters, flow regulators, and sensors. This work also explains the thermal control system architecture with a conceptual design, arrangement of all the components, and thermal analysis for different low orbit conditions. Sizing and extensive trade studies for the components are conducted and the results have shown that the Single-phase MPFL system is able to handle the given thermal loads and maintain the satellite’s interface temperature within the desired limit.

Keywords: active thermal control system, satellite thermal, mechanically pumped fluid loop system, cryogenics, cryocooler

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Authors: Ivana Hrebickova, Maria Sevcikova, Romana Slamberova

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The present study was aimed at evaluation of cognitive changes following scheduled neonatal methamphetamine exposure in combination with long-term exposure in adulthood of female Wistar rats. Pregnant mothers were divided into two groups: group with indirect exposure (methamphetamine in dose 5 mg/ml/kg, saline in dose 1 ml/kg) during early lactation period (postnatal day 1–11) - progeny of these mothers were exposed to the effects of methamphetamine or saline indirectly via the breast milk; and the second group with direct exposure – all mothers were left intact for the entire lactation period, while progeny was treated with methamphetamine (5 mg/ml/kg) by injection or the control group, which was received needle pick (shame, not saline) at the same time each day of period of application (postnatal day 1–11). Learning ability and memory consolidation were tested in the Morris Water Maze, which consisted of three types of tests: ‘Place Navigation Test ‘; ‘Probe Test ‘; and ‘Memory Recall Test ‘. Adult female progeny were injected daily, after completion last trial with saline or methamphetamine (1 mg/ml/kg). We compared the effects of indirect/direct neonatal methamphetamine exposure and adult methamphetamine treatment on cognitive function of female rats. Statistical analyses showed that neonatal methamphetamine exposure worsened spatial learning and ability to remember the position of the platform. The present study demonstrated that direct methamphetamine exposure has more significant impact on process of learning and memory than indirect exposure. Analyses of search strategies (thigmotaxis, scanning) used by females during the Place Navigation Test and Memory Recall Test confirm all these results.

Keywords: methamphetamine, Morris water maze, neonatal exposure, strategies, Wistar rats

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Authors: S. L. J. Tan, N. Billa, C. J. Roberts

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Oral delivery of amphotericin B (AmpB) potentially eliminates constraints and side effects associated with intravenous administration, but remains challenging due to the physicochemical properties of the drug such that it results in meagre bioavailability (0.3%). In an advanced formulation, 1) nanostructured lipid carriers (NLC) were formulated as they can accommodate higher levels of cargoes and restrict drug expulsion and 2) a mucoadhesion feature was incorporated so as to impart sluggish transit of the NLC along the gastrointestinal tract and hence, maximize uptake and improve bioavailability of AmpB. The AmpB-loaded NLC formulation was successfully formulated via high shear homogenisation and ultrasonication. A chitosan coating was adsorbed onto the formed NLC. Physical properties of the formulations; particle size, zeta potential, encapsulation efficiency (%EE), aggregation states and mucoadhesion as well as the effect of the variable pH on the integrity of the formulations were examined. The particle size of the freshly prepared AmpB-loaded NLC was 163.1 ± 0.7 nm, with a negative surface charge and remained essentially stable over 120 days. Adsorption of chitosan caused a significant increase in particle size to 348.0 ± 12 nm with the zeta potential change towards positivity. Interestingly, the chitosan-coated AmpB-loaded NLC (ChiAmpB NLC) showed significant decrease in particle size upon storage, suggesting 'anti-Ostwald' ripening effect. AmpB-loaded NLC formulation showed %EE of 94.3 ± 0.02 % and incorporation of chitosan increased the %EE significantly, to 99.3 ± 0.15 %. This suggests that the addition of chitosan renders stability to the NLC formulation, interacting with the anionic segment of the NLC and preventing the drug leakage. AmpB in both NLC and ChiAmpB NLC showed polyaggregation which is the non-toxic conformation. The mucoadhesiveness of the ChiAmpB NLC formulation was observed in both acidic pH (pH 5.8) and near-neutral pH (pH 6.8) conditions as opposed to AmpB-loaded NLC formulation. Hence, the incorporation of chitosan into the NLC formulation did not only impart mucoadhesive property but also protected against the expulsion of AmpB which makes it well-primed as a potential oral delivery system for AmpB.

Keywords: Amphotericin B, mucoadhesion, nanostructured lipid carriers, oral delivery

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Authors: Virginia Martin Torrejon, Song Hang

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Gelatine foams are widely explored materials due to their biodegradability, biocompatibility, and availability. They exhibit outstanding properties and are currently subject to increasing scientific research due to their potential use in different applications, such as biocompatible cellular materials for biomedical products or biofoams as an alternative to fossil-fuel-derived packaging. Gelatine is a highly surface-active polymer, and its concentrated solutions usually do not require surfactants to achieve low surface tension. Still, anionic surfactants like sodium dodecyl sulfate (SDS) strongly interact with gelatine, impacting its viscosity and rheological properties and, in turn, their foaming behaviour. Foaming behaviour is a key parameter for cellular solids produced by mechanical foaming as it has a significant effect on the processing and properties of cellular materials. Foamability mainly impacts the density and the mechanical properties of the foams, while foam stability is crucial to achieving foams with low shrinkage and desirable pore morphology. This work aimed to investigate the influence of SDS on the foaming behaviour of concentrated gelatine foams by using a dynamic foam analyser. The study of maximum foam height created, foam formation behaviour, drainage behaviour, and foam structure with regard to bubble size and distribution were carried out in 10 wt% gelatine solutions prepared at different SDS/gelatine concentration ratios. Comparative rheological and viscometry measurements provided a good correlation with the data from the dynamic foam analyser measurements. SDS incorporation at optimum dosages and gelatine gelation led to highly stable foams at high expansion ratios. The viscosity increase of the hydrogel solution at SDS content increased was a key parameter for foam stabilization. In addition, the impact of SDS content on gelling time and gel strength also considerably impacted the foams' stability and pore structure.

Keywords: dynamic foam analyser, gelatine foams stability and foamability, gelatine-surfactant foams, gelatine-SDS rheology, gelatine-SDS viscosity

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Authors: Bingying Liu, Dandong Ge, Xinlan Zhang, Haoyang Liang

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Over the past two years, a new generation of No-Pile Bike sharing, represented by the Ofo, Mobike and HelloBike, has sprung up in various cities in China, and spread rapidly in countries such as Britain, Japan, the United States and Singapore. As a new green public transportation mode, bike sharing can bring a series of benefits to urban space. At first, this paper analyzes the specific impact of bike sharing on urban space in China. Based on the market research and data analyzing, it is found that bike sharing can improve the quality of urban space in three aspects: expanding the radius of public transportation service, filling service blind spots, alleviating urban traffic congestion, and enhancing the vitality of urban space. On the other hand, due to the immature market and the imperfect system, bike sharing has gradually revealed some difficulties, such as parking chaos, malicious damage, safety problems, imbalance between supply and demand, and so on. Then the paper investigates the characteristics of shared bikes, business model, operating mechanism on Chinese market currently. Finally, in order to make bike sharing serve urban construction better, this paper puts forward some specific countermeasures from four aspects. In terms of market operations, it is necessary to establish a public-private partnership model and set up a unified bike-sharing integrated management platform. From technical methods level, the paper proposes to develop an intelligent parking system for regulating parking. From policy formulation level, establishing a bike-sharing assessment mechanism would strengthen supervision. As to urban planning, sharing data and redesigning slow roadway is beneficial for transportation and spatial planning.

Keywords: bike sharing, impact analysis, improvement strategy, urban space

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Authors: Koustav Pal, Indranil Das

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In recent times, perovskite and double perovskite (DP) systems attracts lot of interest as they provide a rich material platform for studying emergent functionalities like near-room-temperature ferromagnetic (FM) insulators, exchange bias (EB), magnetocaloric effects, colossal magnetoresistance, anisotropy, etc. These interesting phenomena emerge because of complex couplings between spin, charge, orbital, and lattice degrees of freedom in these systems. Various magnetic phenomena such as exchange bias, spin glass, memory effect, colossal magneto-resistance, etc. can be modified and controlled through antisite (B-site) disorder or controlling oxygen concentration of the material. By controlling oxygen concentration in SrFe0.5Co0.5O3 – δ (SFCO) (δ ∼ 0.3), we achieve intrinsic exchange bias effect with a large exchange bias field (∼1.482 Tesla) and giant coercive field (∼1.454 Tesla). Now we modified the B-site by introducing 10% iridium in the system. This modification give rise to the exchange bias field as high as 1.865 tesla and coercive field 1.863 tesla. Our work aims to investigate the effect of oxygen deficiency and B-site effect on exchange bias in oxide materials for potential technological applications. Structural characterization techniques including X-ray diffraction, scanning tunneling microscopy, and transmission electron microscopy were utilized to determine crystal structure and particle size. X-ray photoelectron spectroscopy was used to identify valence states of the ions. Magnetic analysis revealed that oxygen deficiency resulted in a large exchange bias due to a significant number of ionic mixtures. Iridium doping was found to break interaction paths, resulting in various antiferromagnetic and ferromagnetic surfaces that enhance exchange bias.

Keywords: coercive field, disorder, exchange bias, spin glass

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Authors: Azad Mohammed Ali Saber, Lanja Saeed Omer

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The present study deals with numerical method (FE) and experimental investigations on the vibration behavior of carbon fiber-polyester laminated plates. Finite element simulation is done using APDL (Ansys Parametric Design Language) macro codes software version 19. Solid185 layered structural element, including eight nodes, is adopted in this analysis. The experimental work is carried out using (Hand Layup method) to fabricate different layers and orientation angles of composite laminate plates. Symmetric samples include four layers (00/900)s and six layers (00/900/00)s, (00/00/900)s. Antisymmetric samples include one layer (00), (450), two layers (00/900), (-450/450), three layers (00/900/00), four layers (00/900)2, (-450/450)2, five layers (00/900)2.5, and six layers (00/900)3, (-450/450)3. An experimental investigation is carried out using a modal analysis technique with a Fast Fourier Transform Analyzer (FFT), Pulse platform, impact hammer, and accelerometer to obtain the frequency response functions. The influences of different parameters such as the number of layers, aspect ratio, modulus ratio, ply orientation, and different boundary conditions on the dynamic behavior of the CFRPs are studied, where the 1st, 2nd, and 3rd natural frequencies are observed to be the minimum for cantilever boundary condition (CFFF) and the maximum for full clamped boundary condition (CCCC). Experimental results show that the natural frequencies of laminated plates are significantly reliant on the type of boundary conditions due to the restraint effect at the edges. Good agreement is achieved among the finite element and experimental results. All results indicate that any increase in aspect ratio causes a decrease in the natural frequency of the CFRPs plate, while any increase in the modulus ratio or number of layers causes an increase in the fundamental natural frequency of vibration.

Keywords: vibration, composite materials, finite element, APDL ANSYS

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Authors: G. Vishnu, T. V. Bharat

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Rainfall plays a major role in the stability of natural slopes in tropical and subtropical regions. These slopes usually have high slope angles and are stable during the dry season. The critical rainfall intensity that might trigger a landslide may not be the highest rainfall. In addition to geological discontinuities and anthropogenic factors, water content, suction, and hydraulic conductivity also play a role. A thorough geotechnical investigation with the principles of unsaturated soil mechanics is required to predict the failures in these cases. The study discusses three landslide events that had occurred in residual hills of Guwahati, India. Rainfall data analysis, history image analysis, land use, and slope maps of the region were analyzed and discussed. The landslide occurred on June (24, 26, and 28) 2020, on the respective sites, but the highest rainfall was on June (6 and 17) 2020. The factors that lead to the landslide occurrence is the combination of critical events initiated with rainfall, causing a reduction in suction. The sites consist of a mixture of rocks and soil. The slope failure occurs due to the saturation of the soil layer leading to loss of soil strength resulting in the flow of the entire soil rock mass. The land-use change, construction activities, other human and natural activities that lead to faster disintegration of rock mass may accelerate the landslide events. Landslides in these slopes are inevitable, and the development of an early warning system (EWS) to save human lives and resources is a feasible way. The actual time of failure of a slope can be better predicted by considering all these factors rather than depending solely on the rainfall intensities. An effective EWS is required with less false alarms in these regions by proper instrumentation of slope and appropriate climatic downscaling.

Keywords: early warning system, historic image analysis, slope instrumentation, unsaturated soil mechanics

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Authors: Abdallah Al-ZoubI, Mamoun Dmour

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The spectrum of IoT devices is becoming widely diversified, entering almost all possible fields and finding applications in industry, health, finance, logistics, education, to name a few. The IoT active endpoint sensors and devices exceeded the 12 billion mark in 2021 and are expected to reach 27 billion in 2025, with over $34 billion in total market value. This sheer rise in numbers and use of IoT devices bring with it considerable concerns regarding data storage, analysis, manipulation and protection. IoT Blockchain-based systems have recently been proposed as a decentralized solution for large-scale data storage and protection. COVID-19 has actually accelerated the desire to utilize IoT devices as it impacted both demand and supply and significantly affected several regions due to logistic reasons such as supply chain interruptions, shortage of shipping containers and port congestion. An IoT-blockchain system is proposed to handle big data generated by a distributed network of sensors and controllers in an interactive manner. The system is designed using the Ethereum platform, which utilizes smart contracts, programmed in solidity to execute and manage data generated by IoT sensors and devices. such as Raspberry Pi 4, Rasbpian, and add-on hardware security modules. The proposed system will run a number of applications hosted by a local machine used to validate transactions. It then sends data to the rest of the network through InterPlanetary File System (IPFS) and Ethereum Swarm, forming a closed IoT ecosystem run by blockchain where a number of distributed IoT devices can communicate and interact, thus forming a closed, controlled environment. A prototype has been deployed with three IoT handling units distributed over a wide geographical space in order to examine its feasibility, performance and costs. Initial results indicated that big IoT data retrieval and storage is feasible and interactivity is possible, provided that certain conditions of cost, speed and thorough put are met.

Keywords: IoT devices, blockchain, Ethereum, big data

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Authors: Safieh Javadinejad

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In order to make well-informed decisions respecting long-term system planning, resource managers and policy creators necessitate to comprehend the interconnections among energy and water utilization and manufacture—and also the energy-water nexus. Planning and assessment issues contain the enhancement of strategies for declining the water and energy system’s vulnerabilities to climate alteration with also emissions of decreasing greenhouse gas. In order to deliver beneficial decision support for climate adjustment policy and planning, understanding the regionally-specific features of the energy-water nexus, and the history-future of the water and energy source systems serving is essential. It will be helpful for decision makers understand the nature of current water-energy system conditions and capacity for adaptation plans for future. This research shows an integrated hydrology/energy modeling platform which is able to extend water-energy examines based on a detailed illustration of local circumstances. The modeling links the Water Evaluation and Planning (WEAP) and the Long Range Energy Alternatives Planning (LEAP) system to create full picture of water-energy processes. This will allow water managers and policy-decision makers to simply understand links between energy system improvements and hydrological processing and realize how future climate change will effect on water-energy systems. The Zayandeh Rud river basin in Iran is selected as a case study to show the results and application of the analysis. This region is known as an area with large integration of both the electric power and water sectors. The linkages between water, energy and climate change and possible adaptation strategies are described along with early insights from applications of the integration modeling system.

Keywords: climate impacts, hydrology, water systems, adaptation planning, electricity, integrated modeling

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Authors: Dhanya Nair, Nicholas Mirchandani

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Musical haptic systems can enhance a listener’s musical experience while providing an alternative platform for the hearing impaired to experience music. Current music tactile technologies focus on representing tactile metronomes to synchronize performers or encoding musical notes into distinguishable (albeit distracting) tactile patterns. There is growing interest in the development of musical haptic systems to augment the auditory experience, although the haptic-music relationship is still not well understood. This paper represents a tactile music interface that provides vibrations to multiple fingertips in synchronicity with auditory music. Like an audio equalizer, different frequency bands are filtered out, and the power in each frequency band is computed and converted to a corresponding vibrational strength. These vibrations are felt on different fingertips, each corresponding to a different frequency band. Songs with music from different spectrums, as classified by their energy and valence, were used to test the effectiveness of the system and to understand the relationship between music and tactile sensations. Three participants were trained on one song categorized as sad (low energy and low valence score) and one song categorized as happy (high energy and high valence score). They were trained both with and without auditory feedback (listening to the song while experiencing the tactile music on their fingertips and then experiencing the vibrations alone without the music). The participants were then tested on three songs from both categories, without any auditory feedback, and were asked to classify the tactile vibrations they felt into either category. The participants were blinded to the songs being tested and were not provided any feedback on the accuracy of their classification. These participants were able to classify the music with 100% accuracy. Although the songs tested were on two opposite spectrums (sad/happy), the preliminary results show the potential of utilizing a vibrotactile equalizer, like the one presented, for augmenting musical experience while furthering the current understanding of music tactile relationship.

Keywords: haptic music relationship, tactile equalizer, tactile music, vibrations and mood

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Authors: B. Self, V. Fleming, C. Maxwell

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The fourth clause of the UK 1967 Abortion Act allows individuals (including health care practitioners) to conscientiously object to participating in an abortion. Individuals are able to object if they consider that participating is incompatible with their religious, moral, philosophical, ethical, or personal beliefs. Currently, there is no research on service users’ opinions and understandings of conscientious objection or the impact of conscientious objection from the UK service users’ perspective. This perspective is imperative in understanding the real-world consequences and impact of conscientious objection and essential when creating policy and guidelines. This qualitative research took a liberal feminist approach. It provided a platform for service users to share their experiences of abortion and conscientious objection, as well as their opinions and understandings of conscientious objection. The method employed was semi-structured interviews. Findings indicated that conscientious objection could work in practice. However, it is currently failing some individuals, as health care practitioners are not always referring and informing service users. Participants didn’t experience burdens such as long waiting times and were still able to access legal abortion. However, participants did experience negative emotional effects, as they were often left feeling scared, angry, and hopeless when they were not referred. Moreover, participants’ opinions on conscientious objection in the UK varied greatly. The majority supported the most common approach within the literature and in practice, whereby health care practitioners are able to object so long as they refer and inform the service user. However, the opinion that health care practitioners should not be allowed to object or should be able to object without referring and informing was also present. Without this research, the impact that conscientious objection is having on service users in the UK and service users’ opinions on conscientious objection wouldn’t be known. These findings will be used to inform national policy and guidelines, making access to abortion fairer and safer for all.

Keywords: conscientious objection, abortion, medical ethics, reproductive justice

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Authors: Alberto Enrique Molina Lozano, María Teresa Cortés Montañez

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Polyaniline (PANI) photoelectrodes were electrochemically synthesized through electrodeposition employing three techniques: chronoamperometry (CA), cyclic voltammetry (CV), and potential pulse (PP) methods. The substrate used for electrodeposition was a fluorine-doped tin oxide (FTO) glass with dimensions of 2.5 cm x 1.3 cm. Subsequently, structural and optical characterization was conducted utilizing Fourier-transform infrared (FTIR) spectroscopy and UV-visible (UV-vis) spectroscopy, respectively. The FTIR analysis revealed variations in the molar ratio of benzenoid to quinonoid rings within the PANI polymer matrix, indicative of differing oxidation states arising from the distinct electropolymerization methodologies employed. In the optical characterization, differences in the energy band gap (Eg) values and positions of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) were observed, attributable to variations in doping levels and structural irregularities introduced during the electropolymerization procedures. To assess the charge transfer properties of the PANI photoelectrodes, electrochemical impedance spectroscopy (EIS) experiments were carried out within a 0.1 M sodium sulfate (Na₂SO₄) electrolyte. The results displayed a substantial decrease in charge transfer resistance with the PANI coatings compared to uncoated substrates, with PANI obtained through cyclic voltammetry (CV) presenting the lowest charge transfer resistance, contrasting PANI obtained via chronoamperometry (CA) and potential pulses (PP). Subsequently, the photoactive response of the PANI photoelectrodes was measured through linear sweep voltammetry (LSV) and chronoamperometry. The photoelectrochemical measurements revealed a discernible photoactivity in all PANI-coated electrodes. However, PANI electropolymerized through CV displayed the highest photocurrent. Interestingly, PANI derived from chronoamperometry (CA) exhibited the highest degree of stable photocurrent over an extended temporal interval.

Keywords: PANI, photocurrent, photoresponse, charge separation, recombination

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Authors: Sharif Abdelghany

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Polymeric nanoparticles have been widely investigated as a controlled release drug delivery platform for the treatment of tuberculosis (TB). These nanoparticles were also readily internalised into macrophages, leading to high intracellular drug concentration. In this study two anti-TB drugs, amikacin and moxifloxacin were encapsulated into PLGA nanoparticles. The novelty of this work appears in: (1) the efficient encapsulation of two hydrophilic second-line anti-TB drugs, and (2) intramacrophage delivery of this synergistic combination potentially for rapid treatment of multi-drug resistant TB (MDR-TB). Two water-oil-water (w/o/w) emulsion strategies were employed in this study: (1) alginate coated PLGA nanoparticles, and (2) alginate entrapped PLGA nanoparticles. The average particle size and polydispersity index (PDI) of the alginate coated PLGA nanoparticles were found to be unfavourably high with values of 640 ± 32 nm and 0.63 ± 0.09, respectively. In contrast, the alginate entrapped PLGA nanoparticles were within the desirable particle size range of 282 - 315 nm and the PDI was 0.08 - 0.16, and therefore were chosen for subsequent studies. Alginate entrapped PLGA nanoparticles yielded a drug loading of over 10 µg/mg powder for amikacin, and more than 5 µg/mg for moxifloxacin and entrapment efficiencies range of approximately 25-31% for moxifloxacin and 51-59% for amikacin. To study macrophage uptake efficiency, the nanoparticles of alginate entrapped nanoparticle formulation were loaded with acridine orange as a marker, seeded to THP-1 derived macrophages and viewed under confocal microscopy. The particles were readily internalised into the macrophages and highly concentrated in the nucleus region. Furthermore, the anti-mycobacterial activity of the drug-loaded particles was evaluated using M. tuberculosis-infected macrophages, which revealed a significant reduction (4 log reduction) of viable bacterial count compared to the untreated group. In conclusion, the amikacin-moxifloxacin alginate entrapped PLGA nanoparticles are promising for further in vivo studies.

Keywords: moxifloxacin and amikacin, nanoparticles, multidrug resistant TB, PLGA

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Authors: Moiseenko F. V., Volkov N. M., Zhabina A. S., Stepanova E. O., Kirillov A. V., Myslik A. V., Artemieva E. V., Agranov I. R., Oganesyan A. P., Egorenkov V. V., Abduloeva N. H., Aleksakhina S. Yu., Ivantsov A. O., Kuligina E. S., Imyanitov E. N., Moiseyenko V. M.

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Analysis of ctDNA in patients with NSCLC is an emerging biomarker. Multiple research efforts of quantitative or at least qualitative analysis before and during the first periods of treatment with TKI showed the prognostic value of ctDNA clearance. Still, these important results are not incorporated in clinical standards. We evaluated the role of ctDNA in EGFR-mutated NSCLC receiving first-line TKI. Firstly, we analyzed sequential plasma samples from 30 patients that were collected before intake of the first tablet (at baseline) and at 6, 12, 24, 36, and 48 hours after the “starting point.” EGFR-M+ allele was measured by ddPCR. Afterward, we included sequential qualitative analysis of ctDNA with cobas® EGFR Mutation Test v2 from 99 NSCLC patients before the first dose, after 2 and 4 months of treatment, and on progression. Early response analysis showed the decline of EGFR-M+ level in plasma within the first 48 hours of treatment in 11 subjects. All these patients showed objective tumor response. 10 patients showed either elevation of EGFR-M+ plasma concentration (n = 5) or stable content of circulating EGFR-M+ after the start of the therapy (n = 5); only 3 of these patients achieved an objective response (p = 0.026) when compared to the former group). The rapid decline of plasma EGFR-M+ DNA concentration also predicted for longer PFS (13.7 vs. 11.4 months, p = 0.030). Long-term ctDNA monitoring showed clinically significant heterogeneity of EGFR-mutated NSCLC treated with 1st line TKIs in terms of progression-free and overall survival. Patients without detectable ctDNA at baseline (N = 32) possess the best prognosis on the duration of treatment (PFS: 24.07 [16.8-31.3] and OS: 56.2 [21.8-90.7] months). Those who achieve clearance after two months of TKI (N = 42) have indistinguishably good PFS (19.0 [13.7 – 24.2]). Individuals who retain ctDNA after 2 months (N = 25) have the worst prognosis (PFS: 10.3 [7.0 – 13.5], p = 0.000). 9/25 patients did not develop ctDNA clearance at 4 months with no statistical difference in PFS from those without clearance at 2 months. Prognostic heterogeneity of EGFR-mutated NSCLC should be taken into consideration in planning further clinical trials and optimizing the outcomes of patients.

Keywords: NSCLC, EGFR, targeted therapy, ctDNA, prognosis

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