Search results for: human enteric pathogens (HEPs)

Authors: R. B. Mishra

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Hidden Markov Model (HMM) has been used in prediction and determination of states that generate different neural activations as well as mental working conditions. This paper addresses two applications of HMM; one to determine the optimal sequence of states for two neural states: Active (AC) and Inactive (IA) for the three emission (observations) which are for No Working (NW), Waiting (WT) and Working (W) conditions of human beings. Another is for the determination of optimal sequence of intentionality i.e. Believe (B), Desire (D), and Intention (I) as the states and three observational sequences: NW, WT and W. The computational results are encouraging and useful.

Keywords: hiden markov model, believe desire intention, neural activation, simulation

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Authors: Seyedahmad Hosseini, Mohammadjavad Sotoudeheian

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Introduction: Allergic asthma is a heterogeneous immuno-inflammatory disease based on Th-2-mediated inflammation. Histopathologic abnormalities of the airways characteristic of asthma include epithelial damage and subepithelial collagen deposition. Objectives: Human bronchial epithelial cell genome expression of TNF‑α, IL‑6, ICAM‑1, VCAM‑1, nuclear factor (NF)‑κB signaling pathways up-regulate during inflammatory cascades. Moreover, immunofluorescence assays confirmed the nuclear translocation of NF‑κB p65 during inflammatory responses. An absolute LDH leakage assays suggestedLPS-inducedcells injury, and the associated mechanisms are co-incident events. LPS-induced phosphorylation of ERKand JNK causes inflammation in epithelial cells through inhibition of ERK and JNK activation and NF-κB signaling pathway. Furthermore, the inhibition of NF-κB mRNA expression and the nuclear translocation of NF-κB lead to anti-inflammatory events. Likewise, activation of SUMF2 which inhibits IL-13 and reduces Th2-cytokines, NF-κB, and IgE levels to ameliorate asthma. On the other hand, TNFα-induced mucus production reduced NF-κB activation through inhibition of the activation status of Rac1 and IκBα phosphorylation. In addition, bradykinin B2 receptor (B2R), which mediates airway remodeling, regulates through NF-κB. Bronchial B2R expression is constitutively elevated in allergic asthma. In addition, certain NF-κB -dependent chemokines function to recruit eosinophils in the airway. Besides, bromodomain containing 4 (BRD4) plays a significant role in mediating innate immune response in human small airway epithelial cells as well as transglutaminase 2 (TG2), which is detectable in saliva. So, the guanine nucleotide-binding regulatory protein α-subunit, Gα16, expresses a κB-driven luciferase reporter. This response was accompanied by phosphorylation of IκBα. Furthermore, expression of Gα16 in saliva markedly enhanced TNF-α-induced κB reporter activity. Methods: The applied method to form NF-κB activation is the electromobility shift assay (EMSA). Also, B2R-BRD4-TG2 complex detection by immunoassay method within saliva with EMSA of NF-κB activation may be a novel biomarker for asthma diagnosis and follow up. Conclusion: This concept introduces NF-κB signaling pathway as potential asthma biomarkers and promising targets for the development of new therapeutic strategies against asthma.

Keywords: NF-κB, asthma, saliva, T-helper

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Authors: Nahla Elsherbiny, Ahmed Ahmed, Hamada Mohammed, Mohamed Ali

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Background: The enterococci may be considered as opportunistic agents particularly in immunocompromised patients. It is one of the top three pathogens causing many healthcare associated infections (HAIs). Resistance to several commonly used antimicrobial agents is a remarkable characteristic of most species which may carry various genes contributing to virulence. Objectives: to determine the prevalence of enterococci species in different intensive care units (ICUs) causing health care-associated infections (HAIs), intestinal carriage and environmental contamination. Also, to study the antimicrobial susceptibility pattern of the isolates with special reference to vancomycin resistance. In addition to phenotypic and genotypic detection of gelatinase, cytolysin and biofilm formation among isolates. Patients and Methods: This study was carried out in the infection control laboratory at Assiut University Hospitals over a period of one year. Clinical samples were collected from 285 patients with various (HAIs) acquired after admission to different ICUs. Rectal swabs were taken from 14 cases for detection of enterococci carriage. In addition, 1377 environmental samples were collected from the surroundings of the patients. Identification was done by conventional bacteriological methods and confirmed by analytical profile index (API). Antimicrobial sensitivity testing was performed by Kirby Bauer disc diffusion method and detection of vancomycin resistance was done by agar screen method. For the isolates, phenotypic detection of cytolysin, gelatinase production and detection of biofilm by tube method, Congo red method and microtiter plate. We performed polymerase chain reaction (PCR) for detection of some virulence genes (gelE, cylA, vanA, vanB and esp). Results: Enterococci caused 10.5% of the HAIs. Respiratory tract infection was the predominant type (86.7%). The commonest species were E.gallinarum (36.7%), E.casseliflavus (30%), E.faecalis (30%), and E.durans (3.4 %). Vancomycin resistance was detected in a total of 40% (12/30) of those isolates. The risk factors associated with acquiring vancomycin resistant enterococci (VRE) were immune suppression (P= 0.031) and artificial feeding (P= 0.008). For the rectal swabs, enterococci species were detected in 71.4% of samples with the predominance of E. casseliflavus (50%). Most of the isolates were vancomycin resistant (70%). Out of a total 1377 environmental samples, 577 (42%) samples were contaminated with different microorganisms. Enterococci were detected in 1.7% (10/577) of total contaminated samples, 50% of which were vancomycin resistant. All isolates were resistant to penicillin, ampicillin, oxacillin, ciprofloxacin, amikacin, erythromycin, clindamycin and trimethoprim-sulfamethaxazole. For the remaining antibiotics, variable percentages of resistance were reported. Cytolysin and gelatinase were detected phenotypically in 16% and 48 % of the isolates respectively. The microtiter plate method showed the highest percentages of detection of biofilm among all isolated species (100%). The studied virulence genes gelE, esp, vanA and vanB were detected in 62%, 12%, 2% and 12% respectively, while cylA gene was not detected in any isolates. Conclusions: A significant percentage of enterococci was isolated from patients and environments in the ICUs. Many virulence factors were detected phenotypically and genotypically among isolates. The high percentage of resistance, coupled with the risk of cross transmission to other patients make enterococci infections a significant infection control issue in hospitals.

Keywords: antimicrobial resistance, enterococci, ICUs, virulence factors

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Authors: Lucas B. Naves, Maria José Abreu

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Reprocessing single-use device has attracted interesting on the medical environment over the last decades. The reprocessing technique was sought in order to reduce the cost of purchasing the new medical device, which can achieve almost double of the price of the reprocessed product. In this manuscript, we have done a literature review, aiming the reuse of medical device that was firstly designed for single use only, but has become, more and more, effective on its reprocessing procedure. We also show the regulation, the countries which allows this procedure, the classification of these device and also the most important issue concerning the re-utilization of medical device, how to minimizing the risk of gram positive and negative bacteria, avoid cross-contamination, hepatitis B (HBV), and C (HCV) virus, and also human immunodeficiency virus (HIV).

Keywords: reusing, reprocessing, single-use medical device, HIV, hepatitis B and C

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Authors: Azhin Hamad Ameen

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This research paper explores the concept of secularism in Iraq, analyzing its historical development, contemporary manifestations, and potential future trajectories. Using a combination of qualitative and quantitative methods, including archival research, interviews with experts and practitioners, and surveys of public opinion, the study examines the complex and often contested relationship between religion, politics, and state power in Iraq. The research finds that secularism has played a significant role in shaping Iraq's political and social landscape over the past century, reflecting both the influence of Western modernity and the challenges of managing religious diversity in a multiethnic, multi-sectarian society. However, the study also reveals that secularism in Iraq is highly contested and fragmented, with competing visions and interpretations among different groups and factions. The research identifies several key factors that have contributed to this fragmentation, including the legacy of colonialism, sectarian conflicts, external interventions, and the rise of Islamist movements. Despite these challenges, the study suggests that secularism continues to hold important potential for promoting democratic governance, protecting human rights, and fostering social cohesion in Iraq. The research concludes by outlining several key policy recommendations for strengthening secularism in Iraq, including promoting interfaith dialogue and tolerance, enhancing public education and civic engagement, and supporting grassroots initiatives for social and political reform. Overall, this research contributes to our understanding of the complex dynamics of secularism in Iraq and highlights the urgent need for innovative and inclusive approaches to promoting democratic governance and social justice in the country.

Keywords: secularism, Iraq, religion, politics, state power, historical development, contemporary manifestations, multiethnic society, multi-sectarian society, western modernity, religious diversity, fragmentation, colonialism, sectarian conflicts, external interventions, Islamist movements, democratic governance, human rights, social cohesion, interfaith dialogue, tolerance, public education, civic engagement, grassroots initiatives, social and political reform

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Authors: Daniela E. Marin, Cornelia Braicu, Gina C. Pistol, Roxana Cojocneanu-Petric, Ioana Berindan Neagoe, Mihail A. Gras, Ionelia Taranu

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Aristolochic acid (AA) is a carcinogenic, mutagenic, and nephrotoxic compound commonly found in the Aristolochiaceae family of plants. AA is frequently associated with urothelial carcinoma of the upper urinary tract in human and animals and is considered as being responsible for Balkan Endemic Nephropathy. The pig provides a good animal model because the porcine urological system is very similar to that of humans, both in aspects of physiology and anatomy. MicroRNA (miRNA) are small non-coding RNAs that have an impact on a wide range of biological processes by regulating gene expression at post-transcriptional level. The objective of this study was to analyze the miRNA profiling in the kidneys of AA intoxicated swine. For this purpose, ten TOPIGS-40 crossbred weaned piglets, 4-week-old, male and females with an initial average body weight of 9.83 ± 0.5 kg were studied for 28 days. They were given ad libitum access to water and feed and randomly allotted to one of the following groups: control group (C) or aristolochic acid group (AA). They were fed a maize-soybean-meal-based diet contaminated or not with 0.25mgAA/kg. To profile miRNA in the kidneys of pigs, microarrays and bioinformatics approaches were applied to analyze the miRNA in the kidney of control and AA intoxicated pigs. After normalization, our results have shown that a total of 5 known miRNAs and 4 novel miRNAs had different profiling in the kidney of intoxicated animals versus control ones. Expression of miR-32-5p, miR-497-5p, miR-423-3p, miR-218-5p, miR-128-3p were up-regulated by 0.25mgAA/kg feed, while the expression of miR-9793-5p, miR-9835-3p, miR-9840-3p, miR-4334-5p was down-regulated. The microRNA profiling in kidney of intoxicated animals was associated with modified expression of target genes as: RICTOR, LASP1, SFRP2, DKK2, BMI1, RAF1, IGF1R, MAP2K1, WEE1, HDGF, BCL2, EIF4E etc, involved in cell division cycle, apoptosis, cell differentiation and cell migration, cell signaling, cancer etc. In conclusion, this study provides new data concerning the microRNA profiling in kidney after aristolochic acid intoxications with important implications for human and animal health.

Keywords: aristolochic acid, kidney, microRNA, swine

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Authors: H. Jeries, N. Volkova, C. G. Iglesias, M. Najjar, M. Rosenblat, M. Aviram, T. Hayek

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Background: Synthetic forms of glucocorticoids (e.g., prednisone, prednisolone) are anti-inflammatory drugs which are widely used in clinical practice. The role of glucocorticoids (GCs) in cardiovascular diseases including atherosclerosis is highly controversial, and their impact on macrophage foam cell formation is still unknown. Our aim was to investigate the effects of prednisone or its active metabolite, prednisolone, on macrophage oxidative stress and lipid metabolism using in-vivo, ex-vivo and in-vitro systems. Methods: The in-vivo study included C57BL/6 mice which were intraperitoneally injected with prednisone or prednisolone (5mg/kg) for 4 weeks, followed by lipid metabolism analyses in the mice aorta, and in peritoneal macrophages (MPM). In the ex-vivo study, we analyzed the effect of serum samples obtained from 9 healthy volunteers before or after treatment with oral prednisone (20mg for 5 days), on J774A.1 macrophage atherogenicity. In-vitro studies were conducted using J774A.1 macrophages, human monocyte derived macrophages (HMDM) and fibroblasts. Cells were incubated with increasing concentrations (0-200 ng/ml) of prednisone or prednisolone, followed by determination of cellular oxidative status, triglyceride and cholesterol metabolism. Results: Prednisone or prednisolone treatment resulted in a significant reduction in triglycerides and mainly in cholesterol cellular accumulation in MPM or in J774A.1 macrophages incubated with human serum. Similar resulted were noted in HMDM or in J774A.1 macrophages which were directly incubated with the GCs. These effects were associated with GCs inhibitory effect on triglycerides and cholesterol biosynthesis rates, throughout downregulation of diacylglycerol acyltransferase1 (DGAT1) expression, and of the sterol regulatory element binding protein (SREBP2) and HMGCR expression, respectively. In parallel to prednisone or prednisolone induced reduction in macrophage triglyceride content, paraoxonase 2 (PON2) expression was significantly upregulated. GCs-induced reduction of cellular triglyceride and cholesterol mass was mediated by the GCs receptors on macrophages since the GCs receptor antagonist (RU 486) abolished these effects. In fibroblasts, unlike macrophages, prednisone or prednisolone showed no anti-atherogenic effects. Conclusions: Prednisone or prednisolone are anti-atherogenic since they protected macrophages from lipid accumulation and foam cell formation.

Keywords: atherosclerosis, cholesterol, foam cell, macrophage, prednisone, prednisolone, triglycerides

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Authors: Jia-Jin He, Tzu-Yuan Stessa Chao

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It is generally accepted that community residents with abundant open space have better health status on average, and thus more and more cities around the world began their pursuit of the greatest possible amount of green space within urban areas through urban planning approach. Nevertheless, only a few studies managed to provide empirical evidence regarding the actual relationship between 'providing' green space and 'improving' human health at city level. There is also lack of evidence of direct positive improvement of health by increasing the amount of green space. For urban planning professional, it is important to understand citizens’ usage behaviour towards green space as a critical evidence for future planning and design strategies. There is a research need to further investigate the amount of green space, user behaviour of green spaces and the health outcome of urban dwellers. To this end, we would like to find out other important factors for urban dwellers’ usage behaviours of green spaces. 'Average green spaces per person' is one of the National well-being Indicators in Taiwan as in many other countries. Through our preliminary research, we collected and analyzed the official data of planned open space coverages, average life expectancy, exercise frequency and obesity ratio in all cities of Taiwan. The study result indicates an interesting finding that Kaohsiung city, the second largest city in Taiwan, tells a completely different story. Citizens in Kaosiung city have more open spaces than any other city through urban planning, yet have relatively unhealthy condition in contrary. Whether it pointed out that the amount of the open spaces per person has would not direct to the health outcome. Therefore, the pre-established view which states that open spaces must have positive effects on human health should be examined more prudently. Hence, this paper intends to explore the relationship between user behaviour of open spaces and citizens’ health conditions by critically analyzing past related literature and collecting selective data from government health database in 2015. We also take Kaohsiung city, as a case study area to conduct statistical analysis first followed by questionnaire survey to gain a better understanding. Finally, we aim to feedback our findings to the current planning system in Taiwan for better health promotion urbanized areas.

Keywords: open spaces, urban planning systems, healthy cities, health outcomes

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Authors: Jo Angouri, Charlotte Kennedy, Shawnea Ting, David Rawlinson, Matthew Booker, Nigel Rees

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Ambulance services need to balance the large volume of emergency (999 in the UK) calls they receive (e.g., West Midlands Ambulance Service reports per day about 4,000 999 calls; about 679,000 calls per year are received in Wales), with dispatching limited resource for on-site intervention to the most critical cases. The process by which Emergency Medical Dispatch (EMD) decisions are made is related to risk assessment and involves the caller and call-taker as well as clinical teams negotiating risk levels on a case-by-case basis. Medical Priority Dispatch System (MPDS – also referred to as Advanced Medical Priority Dispatch System AMPDS) are used in the UK by NHS Trusts (e.,g WAST) to process and prioritise 999 calls. MPDS / AMPDS provide structured protocols for call prioritisation and call management. Protocols/policy frameworks have not been examined before in the way we propose in our project. In more detail, the risk factors that play a role in the EMD negotiation between the caller and call-taker have been analysed in both medical and social science research. Research has focused on the structural, morphological and phonological aspects that could improve, and train, human-to-human interaction or automate risk detection, as well as the medical factors that need to be captured from the caller to inform the dispatch decision. There are two significant gaps in our knowledge that we address in our work: 1. the role of backstage clinical teams in translating the caller/call-taker interaction in their internal risk negotiation and, 2. the role of policy frameworks, protocols and regulations in the framing of institutional priorities and resource allocation. We take a multi method approach and combine the analysis of 999 calls with the analysis of policy documents. We draw on interaction analysis, corpus methodologies and thematic analysis. In this paper, we report on our preliminary findings and focus in particular on the risk factors we have identified and the relationship with the regulations that create the frame within which teams operate. We close the paper with implications of our study for providing evidence-based policy intervention and recommendations for further research.

Keywords: emergency (999) call, interaction analysis, discourse analysis, ambulance dispatch, medical discourse

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Authors: Asena Demirci, Gozen Guner Aktaş, Nur Ayalp

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Nature provides a living space for humans, also in contrast it is destroyed by humans for their personal needs and ambitions. For decreasing these damages against nature, solutions are started to generate and to develop. Moreover, precautions are implemented. After 1960s, especially when the ozone layer got harmed and got thinner by toxic substances coming from man made structures, environmental problems which effected human’s activities of daily living. Thus, this subject about environmental solutions and precautions is becoming a priority issue for scientists. Most of the environmental problems are caused by buildings and factories which are built without any concerns about protecting nature. This situation creates awareness about environmental issues and also the terms like sustainability, Renewable energy show up in building, Construction and architecture sectors to provide environmental protection. In this perspective, the design disciplines also should be respectful to nature and the sustainability. Designs which involve the features like sustainability, renewability and being ecologic have specialties to be less detrimental to the environment rather than the designs which do not involve. Furthermore, these designs produce their own energy for consuming, So they do not use the natural resources. They do not contain harmful substances and they are made of recyclable materials. Thus, they are becoming environmentally friendly structures. There is a common concern among designers about the issue of sustainable design. They believe that the idea of sustainability inhibits the creativity. All works of design resemble each other from the point of aesthetics and technological matters. In addition, there is a concern about design ethics which aesthetic designs cannot be accepted as a priority. For these reasons, there are few designs included the features of being eco-friendly and well-designed and also had design concerns around the world. Despite the other design disciplines, The concept of sustainability is getting more important each day in interior architecture and interior design. As it is known that human being spends 90 % of his life in interior spaces, The importance of that concept in interior spaces is obvious. Aesthetic is another vital concern in interior space design also. Most of the time sustainable materials and sustainable interior design applications conflicts with personal aesthetic parameters. This study aims to discuss the great paradox between the design aesthetic and the sustainable design. Does the sustainable approach in interior design disturbs the design aesthetic? This is one of the most popular questions that have been discussed for a while. With this paper this question will be evaluated with a case study which analyzes the aesthetic perceptions and preferences of the users and designers in sustainable interior spaces.

Keywords: aesthetics, interior design, sustainable design, sustainability

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Authors: Jose Daniel Braga Alves, Joaquim Gois, Alexandre Leite

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This abstract presents the responsible and sustainable mining case study of a Portuguese mine operation, highlighting how mine exploitation can sustainably exist in balance with the environment, aligned with all stakeholders. The mining operation is remotely located in a United Nations (UN) biodiversity reserve, away from major industrial centers or logistical ports, and presents an interesting investigation to assess the balanced mine operation in alignment with all key stakeholders, which presents unique opportunities as well as challenges. Based on the sustainable mining framework, it is intended to detail examples of best practices from Sociedade Mineira de Neves-Corvo (SOMINCOR), demonstrating social acceptance by the local community, health, and safety at work, reduction of environmental impacts and management of mining waste, which directly influence the acceptance and recognition of a sustainable operation. The case study aims to present the SOMINCOR approach to sustainable mining, focusing on social responsibility, considering materials provided by Lundin Mining Corporation (LMC) and SOMINCOR and the socially responsible approach of the mining operations., referencing related international guidelines, UN Sustainable Development Goals. The researchers reviewed LMC's annual Sustainability Reports (2019, 2020 and 2021) and updated information regarding material topics of the most significant interest to internal and external stakeholders. These material topics formed the basis of the corporation-wide sustainability strategy. LMC's Responsible Mining Policy (RMP) was reviewed, focusing on the commitment that guides the approach to responsible operation and management of the Company's business. Social performance, compliance, environmental management, governance, human rights, and economic contribution are principles of the RMP. The Human Rights Risk Impact Assessment (HRRIA), based on frameworks including UN Guiding Principles (UNGP), Voluntary Principles on Security and Human Rights, and a community engagement program implemented (SLO index), was part of this research. The program consists of ongoing surveys and perceptions studies using behavioural science insights, data from which was not available within the timeframe of completing this research. LMC stakeholder engagement standards and grievance mechanisms were also reviewed. Stakeholder engagement and the community's perception are key to this operation to ensure social license to operate (SLO). Preliminary surveys with local communities provided input data for the local development strategy. After the implementation of several initiatives, subsequent surveys were performed to assess acceptance and trust from the local communities and changes to the SLO index. SOMINCOR's operation contributes to 12 out of 17 sustainable development goals. From the assessed and available data, local communities and social engagement are priorities to SOMINCOR. Experience to date shows that the continual engagement with local communities and the grievance mechanisms in place are respected and followed for all concerns presented by any stakeholder. It can be concluded that this underground mine in Portugal complies with applicable regulations and goes beyond them with regard to sustainable development and engagement with key stakeholders.

Keywords: sustainable mining, development goals, portuguese mining, zinc copper

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Authors: Sulmaz Mozaffari, Zahra Mozaffari, Saman Mozaffari

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Training is a counting and orderly process which purpose is to grow all as peals of the students to get the human knowledge and have the social norms. Also to help them grow their talents. Social science as in educational and training science at the sometime is very important for schools and universities. Unfortunately the method which is mostly used for teaching and training at present is student- teacher method and because of its ease the other methods are ignored. This research is to consider the most efficient methods in social science and analyse them. The Results show that the best methods in which the students are present during the teaching procedure.

Keywords: social science, methodology, student base methodology, technology

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Authors: Yuhei Kunihiro, Sorin V. Sabau, Kazuhiro Shibuya

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We study the molecular evolution of insulin from the metric geometry point of view. In mathematics, and particularly in geometry, distances and metrics between objects are of fundamental importance. Using a weaker notion than the classical distance, namely the weighted quasi-metrics, one can study the geometry of biological sequences (DNA, mRNA, or proteins) space. We analyze from the geometrical point of view a family of 60 insulin homologous sequences ranging on a large variety of living organisms from human to the nematode C. elegans. We show that the distances between sequences provide important information about the evolution and function of insulin.

Keywords: metric geometry, evolution, insulin, C. elegans

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Authors: Heide Imai

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The paper will introduce and discuss specific examples of urban practices which take place within the dynamic urban landscape of contemporary Tokyo. The rising interest and importance of derelict places as resilient and creative clusters will be analysed, before relating this to the rediscovery of small urban niches and the emergence of different forms of social entrepreneurs. Secondly, two different case study areas will be introduced before discussing different forms of hybrid lifestyles, social micro scale enterprises and social innovations, understanding the concept of ‘small places of resilience’ as zones of human interaction, desire and care in which spontaneous practices take place.

Keywords: entrepreneurship, social innovation, Tokyo, urban regeneration

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Authors: Michal Kielbik, Izabela Szulc-Kielbik, Anna Brzostek, Jaroslaw Dziadek, Magdalena Klink

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The goal of many research groups in the world is to find new components that are important for survival of mycobacteria in the host cells. Mycobacterium tuberculosis (Mtb) possesses a number of enzymes degrading cholesterol that are considered to be an important factor for its survival and persistence in host macrophages. One of them - cholesterol oxidase (ChoD), although not being essential for cholesterol degradation, is discussed as a virulence compound, however its involvement in macrophages’ response to Mtb is still not sufficiently determined. The recognition of tubercle bacilli antigens by pathogen recognition receptors is crucial for the initiation of the host innate immune response. An important receptor that has been implicated in the recognition and/or uptake of Mtb is Toll-like receptor type 2 (TLR2). Engagement of TLR2 results in the activation and phosphorylation of intracellular signaling proteins including IRAK-1 and -4, TRAF-6, which in turn leads to the activation of target kinases and transcription factors responsible for bactericidal and pro-inflammatory response of macrophages. The aim of these studies was a detailed clarification of the role of Mtb cholesterol oxidase as a virulence factor affecting the TLR2 signaling pathway in human macrophages. As human macrophages the THP-1 differentiated cells were applied. The virulent wild-type Mtb strain (H37Rv), its mutant lacking a functional copy of gene encoding cholesterol oxidase (∆choD), as well as complimented strain (∆choD–choD) were used. We tested the impact of Mtb strains on the expression of TLR2-depended signaling proteins (mRNA level, cytosolic level and phosphorylation status). The cytokine and bactericidal response of THP-1 derived macrophages infected with Mtb strains in relation to TLR2 signaling pathway dependence was also determined. We found that during the 24-hours of infection process the wild-type and complemented Mtb significantly reduced the cytosolic level and phosphorylation status of IRAK-4 and TRAF-6 proteins in macrophages, that was not observed in the case of ΔchoD mutant. Decreasement of TLR2-dependent signaling proteins, induced by wild-type Mtb, was not dependent on the activity of proteasome. Blocking of TLR2 expression, before infection, effectively prevented the induced by wild-type strain reduction of cytosolic level and phosphorylation of IRAK-4. None of the strains affected the surface expression of TLR2. The mRNA level of IRAK-4 and TRAF-6 genes were significantly increased in macrophages 24 hours post-infection with either of tested strains. However, the impact of wild-type Mtb strain on both examined genes was significantly stronger than its ΔchoD mutant. We also found that wild-type strain stimulated macrophages to release high amount of immunosuppressive IL-10, accompanied by low amount of pro-inflammatory IL-8 and bactericidal nitric oxide in comparison to mutant lacking cholesterol oxidase. The influence of wild-type Mtb on this type of macrophages' response strongly dependent on fully active IRAK-1 and IRAK-4 signaling proteins. In conclusion, Mtb using cholesterol oxidase causes the over-activation of TLR2 signaling proteins leading to the reduction of their cytosolic level and activity resulting in the modulation of macrophages response to allow its intracellular survival. Supported by grant: 2014/15/B/NZ6/01565, National Science Center, Poland

Keywords: Mycobacterium tuberculosis, cholesterol oxidase, macrophages, TLR2-dependent signaling pathway

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Authors: Arlinda Memetaj

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A sound system of administrative justice represents a vital element of democratic governance. The proper control of public administration consists not only of a sound civil service framework and legislative oversight, but empowerment of the public and courts to hold public officials accountable for their decision-making through the application of fair administrative procedural rules and the use of appropriate administrative appeals processes and judicial review. The establishment of effective public administration, has been since 1990s among the most 'important and urgent' final strategic objectives of the Republic of Macedonia. To this aim the country has so far adopted a huge series of legislative and strategic documents related to any aspects of the administrative justice system. The latter is designed to strengthen the legal position of citizens, businesses, civic organizations, and other societal subjects. 'Changes and reforms' in this field have been thus the most frequent terms being used in the country for the last more than 20 years. Several years ago the County established Administrative Courts, while permanently amending the Law on the General Administrative procedure (LGAP). The new LGAP was adopted in 2015 and it introduced considerable innovations concerned. The most recent inputs in this regard includes the National Public Administration Reform Strategy 2017 – 2022, one of the key expected result of which includes both providing effective protection of the citizens` rights. In doing the aforesaid however there is still a series of interrelated shortcomings in this regard, such as (just to mention few) the complex appeal procedure, delays in enforcing court rulings, etc. Against the above background, the paper firstly describes the Macedonian institutional and legislative framework in the above field, and then illustrates the shortcomings therein. It finally claims that the current status quo situation may be overcome only if there is a proper implementation of the administrative courts decisions and far stricter international monitoring process thereof. A new approach and strong political commitment from the highest political leadership is thus absolutely needed to ensure the principles of transparency, accountability and merit in public administration. The main method used in this paper is the descriptive, analytical and comparative one due to the very character of the paper itself.

Keywords: administrative justice, administrative procedure, administrative courts/disputes, European Human Rights Court, human rights, monitoring, reform, benefit.

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Authors: Crysovaladou Kefaloudi, Kassiani Mellou, Eirini Saranti-Papasaranti, Athanasios Koustenis, Chrysoula Botsi, Agapios Terzidis

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Recent migration crisis led to a vast migrant – refugees movement to Greece which created an urgent need for hosting settlements. Taken into account the protection of public health from possible pathogens related to water and food supply as well as waste and sewage accumulation, a 'Living Conditions Recording Form' was created in the context of 'PHILOS' European Program funded by the Asylum Migration and Integration Fund (AMIF) of EU’s DG Migration and Home Affairs, in order to assess a number of environmental sanitation parameters, in refugees – migrants camps in mainland. The assessment will be completed until the end of July. From March to June 2017, mobile unit teams comprised of health inspectors of sub-action 2 of “PHILOS” proceeded with the assessment of living conditions in twenty-two out of thirty-one camps and 'Stata' was used for the statistical analysis of obtained information. Variables were grouped into the following categories: 1) Camp administration, 2) hosted population number, 3) accommodation, 4) heating installations, 5) personal hygiene, 6) sewage collection and disposal, 7) water supply, 8) waste collection and management, 9) pest control, 10) fire safety, 11) food handling and safety. Preliminary analysis of the results showed that camp administration was performed in 90% of the camps by a public authority with the coordination of various NGOs. The median number of hosted population was 222 ranging from 62 to 3200, and the median value of hosted population per accommodation type was 4 in 19 camps. Heating facilities were provided in 86.1% of camps. In 18.2 % of the camps, one personal hygiene facility was available per 6 people ranging in the rest of the camps from 1 per 3 to 1 per 20 hosted refugees-migrants. Waste and sewage collection was performed depending on populations demand in an adequate way in all recorded camps. In 90% of camps, water was supplied through the central water supply system. In 85% of camps quantity and quality of water supply inside camps was regularly monitored for microbial and chemical indices. Pest control was implemented in 86.4% of the camps as well as fire safety measures. Food was supplied by catering companies in 50% of the camps, and the quality and quantity food was monitored at a regular basis. In 77% of camps, food was prepared by the hosted population with the availability of proper storage conditions. Furthermore, in all camps, hosted population was provided with personal hygiene items and health sanitary educational programs were implemented in 77.3% of camps. In conclusion, in the majority of the camps, environmental sanitation parameters were satisfactory. However, waste and sewage accumulation, as well as inadequate pest control measures were recorded in some camps. The obtained data have led to a number of recommendations for the improvement of sanitary conditions, disseminated to all relevant stakeholders. Special emphasis was given to hygiene measures implementation during food handling by migrants – refugees, as well as to waste and sewage accumulation taking in to account the population’s cultural background.

Keywords: environmental sanitation parameters, food borne diseases risk assessment, refugee – migrants camps, water borne diseases risk assessment

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Authors: Tayyaba Bari, Muhammad Hamza Anjum, Samra Kanwal, Fakhera Ikram

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Osteoarthritis, a degenerative condition, affects more than 213 million individuals globally. Since articular cartilage has no or limited vessels, therefore, after deteriorating, it is unable to rejuvenate. Traditional approaches for cartilage repair, like autologous chondrocyte implantation, microfracture and cartilage transplantation are often associated with postoperative complications and lead to further degradation. Decellularized human umbilical cord has gained interest as a viable treatment for cartilage repair. Decellularization removes all cellular contents as well as debris, leaving a biologically active 3D network known as extracellular matrix (ECM). This matrix is biodegradable, non-immunogenic and provides a microenvironment for homeostasis, growth and repair. UC derived bioink function as 3D scaffolding material, not only mediates cell-matrix interactions but also adherence, proliferation and propagation of cells for 3D organoids. This study comprises different physical, chemical and biological approaches to optimize the decellularization of human umbilical cord (UC) tissues followed by the solubilization of these tissues to bioink formation. The decellularization process consisted of two cycles of freeze thaw where the umbilical cord at -20˚C was thawed at room temperature followed by dissection in small sections from 0.5 to 1cm. Similarly decellularization with ionic and non-ionic detergents Sodium dodecyl sulfate (SDS) and Triton-X 100 revealed that both concentrations of SDS i.e 0.1% and 1% were effective in complete removal of cells from the small UC tissues. The results of decellularization was further confirmed by running them on 1% agarose gel. Histological analysis revealed the efficacy of decellularization, which involves paraffin embedded samples of 4μm processed for Hematoxylin-eosin-safran and 4,6-diamidino-2-phenylindole (DAPI). ECM preservation was confirmed by Alcian Blue, and Masson’s trichrome staining on consecutive sections and images were obtained. Sulfated GAG’s content were determined by 1,9-dimethyl-methylene blue (DMMB) assay, similarly collagen quantification was done by hydroxy proline assay. This 3D bioengineered scaffold will provide a typical atmosphere as in the extracellular matrix of the tissue, which would be seeded with the mesenchymal cells to generate the desired 3D ink for in vitro and in vivo cartilage regeneration applications.

Keywords: umbilical cord, 3d printing, bioink, tissue engineering, cartilage regeneration

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Authors: Gamze Fahriye Pehlivan, Tulay Canitez

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The traditional Turkish houses becoming unusable are a result of the deterioration of the balanced interaction between users and house (human and house) continuing during the history. Especially depending upon the change in social structure, the houses becoming neglected do not meet the desires of the users and do not have the meaning but the shelter are becoming unusable and are being destroyed. A conservation policy should be developed and renovations should be made in order to pass the traditional houses carrying the quality of a cultural and historical document presenting the social structure, the lifestyle and the traditions of its own age to the next generations and to keep them alive.

Keywords: house, social structural change, social structural, traditional Turkish houses

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Authors: Kirill M. Dubovikov, Ekaterina S. Marchenko, Gulsharat A. Baigonakova

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NiTi alloys are widely used as implants in medicine due to their unique properties such as superelasticity, shape memory effect and biocompatibility. However, despite these properties, one of the major problems is the release of nickel after prolonged use in the human body under dynamic stress. This occurs due to oxidation and cracking of NiTi implants, which provokes nickel segregation from the matrix to the surface and release into living tissues. As we know, nickel is a toxic element and can cause cancer, allergies, etc. One of the most popular ways to solve this problem is to create a corrosion resistant coating on NiTi. There are many coatings of this type, but not all of them have good biocompatibility, which is very important for medical implants. Coatings based on calcium phosphate phases have excellent biocompatibility because Ca and P are the main constituents of the mineral part of human bone. This fact suggests that a Ca-P coating on NiTi can enhance osteogenesis and accelerate the healing process. Therefore, the aim of this study is to investigate the structure of Ca-P coating on NiTi substrate. Plasma assisted radio frequency (RF) sputtering was used to obtain this film. This method was chosen because it allows the crystallinity and morphology of the Ca-P coating to be controlled by the sputtering parameters. It allows us to obtain three different NiTi samples with Ca-P coating. XRD, AFM, SEM and EDS were used to study the composition, structure and morphology of the coating phase. Scratch tests were carried out to evaluate the adhesion of the coating to the substrate. Wettability tests were used to investigate the hydrophilicity of the different coatings and to suggest which of them had better biocompatibility. XRD showed that the coatings of all samples were hydroxyapatite, but the matrix was represented by TiNi intermetallic compounds such as B2, Ti2Ni and Ni3Ti. The SEM shows that the densest and defect-free coating has only one sample after three hours of sputtering. Wettability tests show that the sample with the densest coating has the lowest contact angle of 40.2° and the largest free surface area of 57.17 mJ/m2, which is mostly disperse. A scratch test was carried out to investigate the adhesion of the coating to the surface and it was shown that all coatings were removed by a cohesive mechanism. However, at a load of 30N, the indenter reached the substrate in two out of three samples, except for the sample with the densest coating. It was concluded that the most promising sputtering mode was the third, which consisted of three hours of deposition. This mode produced a defect-free Ca-P coating with good wettability and adhesion.

Keywords: biocompatibility, calcium phosphate coating, NiTi alloy, radio frequency sputtering.

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Authors: K. M. Anusha, R. Krishnaveni

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Crossing a decade of the 21st century, the paradigm of human resources can be seen evolving with the strategic gene induced into it. There seems to be a radical shift descending as the corporate sector calls on its HR team to become strategic rather than administrative. This transferal eventually requires the metrics employed by these HR teams not to be just operationally reactive but to be aligned to an evidence-based strategic thinking. Realizing the growing need for a prescriptive metric model for effective HR analytics, this study has designed a conceptual framework for a basic metric model that can assist IT-HRM professionals to transition to a practice of evidence-based decision-making to enhance organizational performance.

Keywords: metric model, evidence based HR, HR analytics, strategic HR practices, IT sector

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Authors: Leila Sadeghi

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Gender equality is a critical concern in the workplace, particularly in Iran, where legal and social barriers contribute to significant disparities. This abstract presents a case study of Dahi Bondad Co., a company based in Tehran, Iran that recognized the urgency of addressing the gender gap within its organization. Through a comprehensive investigation, the company identified issues related to biased recruitment, pay disparities, promotion biases, internal barriers, and everyday boundaries. This abstract highlights the strategies implemented by Dahi Bondad Co. to combat these challenges and foster gender equality. The company revised its recruitment policies, eliminated gender-specific language in job advertisements, and implemented blind resume screening to ensure equal opportunities for all applicants. Comprehensive pay equity analyses were conducted, leading to salary adjustments based on qualifications and experience to rectify pay disparities. Clear and transparent promotion criteria were established, and training programs were provided to decision-makers to raise awareness about unconscious biases. Additionally, mentorship and coaching programs were introduced to support female employees in overcoming self-limiting beliefs and imposter syndrome. At the same time, practical workshops and gamification techniques were employed to boost confidence and encourage women to step out of their comfort zones. The company also recognized the importance of dress codes and allowed optional hijab-wearing, respecting local traditions while promoting individual freedom. As a result of these strategies, Dahi Bondad Co. successfully fostered a more equitable and empowering work environment, leading to increased job satisfaction for both male and female employees within a short timeframe. This case study serves as an example of practical approaches that human resource managers can adopt to address gender inequality in the workplace, providing valuable insights for organizations seeking to promote gender equality in similar contexts.

Keywords: gender equality, human resource strategies, legal barrier, social barrier, successful result, successful strategies, workplace in Iran

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Authors: G. A. Gevorgyan, A. S. Mamyan, L. G. Stepanyan, L. R. Hambaryan

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Bacterio- and phytoplankton growth rates in 'Yerevanyan lich' reservoir and the Hrazdan river in Yerevan city, Armenia were investigated in April and June-August, 2015. Phytoplankton sampling and analysis were performed by the standard methods accepted in hydrobiological studies. The quantitative analysis of aerobic, coliform and E. coli bacteria is done by the 'RIDA COUNT' medium sheets (coated with ready-to-use culture medium). The investigations showed that the insufficient management of household discharges in Yerevan city caused the organic and fecal pollution of the Hrazdan river in this area which in turn resulted in an increase in bacterial count and increased sanitary and pathogenic risks to the environment and human health. During the investigation in April, the representatives of diatom algae prevailed quantitatively in the coastal area of 'Yerevanyan lich' reservoir, nevertheless, a significant change in the phytoplankton community in June occurred: due to green algae bloom in the reservoir, the quantitative parameters of phytoplankton increased significantly. This was probably conditioned by a seasonal increase in the water temperature in the conditions of the sufficient concentration of nutrients. However, a succession in phytoplankton groups during July-August occurred, and a dominant group (according to quantitative parameters) in the phytoplankton community was changed as follows: green algae-diatom algae-blue-green algae. Rapid increase in the quantitative parameters of diatom and blue-green algae in the reservoir may have been conditioned by increased organic matter level resulted from green algae bloom. Algal bloom in 'Yerevanyan lich' reservoir caused changes in phytoplankton community and an increase in bacterioplankton count not only in the reservoir but also in the Hrazdan river sites located in the downstream from the reservoir. Thus, the insufficient management of urban discharges and aquatic ecosystems in Yerevan city led to unfavorable changes in water quality and microbial and phytoplankton communities in “Yerevanyan lich” reservoir and the Hrazdan river which in turn caused increased sanitary and pathogenic risks to the environment and human health.

Keywords: algal bloom, bacterioplankton, phytoplankton, Hrazdan river, Yerevanyan lich reservoir

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Authors: Ihab Elaff

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Simulating the heart’s electrical stimulation is essential in modeling and evaluating the electrophysiology behavior of the heart. For achieving that, there are two structures in concern: the ventricles’ Myocardium, and the ventricles’ Conduction Network. Ventricles’ Myocardium has been modeled as anisotropic material from Diffusion Tensor Imaging (DTI) scan, and the Conduction Network has been extracted from DTI as a case-based structure based on the biological properties of the heart tissues and the working methodology of the Magnetic Resonance Imaging (MRI) scanner. Results of the produced activation were much similar to real measurements of the reference model that was presented in the literature.

Keywords: diffusion tensor, DTI, heart, conduction network, excitation propagation

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Authors: Mohammad Kazem Mohammadi

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The use of anticancer agents forms an important part of the treatment of cancer of various types. Uranyl Complexes with DPHMP ligand have been used for the prevention and treatment of cancers. U(IV) metal complexes prepared by reaction of uranyl salt UO2 (NO3)2.6H2O with DPHMP in dry acetonitrile. Characterization of the ligand and its complexes was made by microanalyses, FT-IR, 1H NMR, 13C NMR and UV–Visible spectroscopy. These new complex showed excellent antitumor activity against two kinds of cancer cells that that are HT29:Haman colon adenocarcinoma cell line and T47D:human breast adenocarcinoma cell line.

Keywords: uranyl complexes, DPHMP ligand, antitumor activity, HT29, T47D

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Authors: Medjram Sofiane, Babahenini Mohamed Chaouki, Mohamed Benali Yamina

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Skin detection is an important task for computer vision systems. A good method for skin detection means a good and successful result of the system. The colour is a good descriptor that allows us to detect skin colour in the images, but because of lightings effects and objects that have a similar colour skin, skin detection becomes difficult. In this paper, we proposed a method using the YCbCr colour space for skin detection and lighting effects elimination, then we use the information of texture to eliminate the false regions detected by the YCbCr colour skin model.

Keywords: skin detection, YCbCr, GLCM, texture, human skin

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Authors: Gashaw Sisay Zenebe

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Northern-Ethiopian conflict that broke out on 04 November 2020 between the central government and TPLF caused destruction beyond imagination in all aspects; millions of people have been killed, including civilians, mainly women, and children. Civilians have been indiscriminately attacked simply because of their ethnic or religious identity. Warrying parties committed serious crimes of international concern opposite to International Humanitarian Law (IHL). A House of People Representatives (HPR) declared that the terrorist Tigrean Defense Force (TDF), encompassing all segments of its people, waged war against North Gondar through human flooding. On Aug 30, 2021, after midnight, TDF launched a surprise attack against Chena People who had been drunk and deep slept due to the annual festivity. Unlike the lowlands, however, ENDF conjoined the local people to fight TDF in these Highland areas. This research examines identity politics and the consequential genocidal massacre of Chena, including its human and physical destructions that occurred as a result of the armed conflict. As such, the study could benefit international entities by helping them develop a better understanding of what happened in Chena and trigger interest in engaging in ensuring the accountability and enforcement of IHL in the future. Preserving fresh evidence will also serve as a starting point on the road to achieving justice either nationally or internationally. To study the Chena case evaluated against IHL rules, a combination of qualitative and doctrinal research methodology has been employed. The study basically follows a unique sampling case study which has used primary data tools such as observation, interview, key-informant interview, FGD, and battle-field notes. To supplement, however, secondary sources, including books, journal articles, domestic laws, international conventions, reports, and media broadcasts, were used to give meaning to what happened on the ground in light of international law. The study proved that the war was taking place to separate Tigray from Ethiopia. While undertaking military operations to achieve this goal, mass killings, genocidal acts, and war crimes were committed over Chena and approximate sites in the Dabat district of North Gondar. Thus, hundreds of people lost their lives to the brutalities of mass killings, hundreds of people were subjected to a forcible disappearance, and tens of thousands of people were forced into displacement. Furthermore, harsh beatings, forced labor, slavery, torture, rape, and gang rape have been reported, and generally, people are subjected to pass cruel, inhuman, and degrading treatment and punishment. Also, what is so unique is that animals were indiscriminately killed completely, making the environment unsafe for human survival because of pollution and bad smells and the consequent diseases such as Cholera, Flu, and Diarrhea. In addition to TDF, ENDF’s shelling has caused destruction to farmers’ houses & claimed lives. According to humanitarian principles, acts that can establish MACs and war crimes were perpetrated. Generally, the war in this direction has shown an absolute disrespect for international law norms.

Keywords: genocide, war crimes, Tigray Defense Force, Chena, IHL

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Authors: E. Locatelli, I. Monaco, R. C. Martin, Y. Li, R. Pini, M. Chiariello, M. Comes Franchini

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Despite the many advantages of application of nanomaterials in the field of nanomedicine, increasing concerns have been expressed on their potential adverse effects on human health. There is urgency for novel green strategies toward novel materials with enhanced biocompatibility using safe reagents. Photothermal ablation therapy, which exploits localized heat increase of a few degrees to kill cancer cells, has appeared recently as a non-invasive and highly efficient therapy against various cancer types; anyway new agents able to generate hyperthermia when irradiated are needed and must have precise biocompatibility in order to avoid damage to healthy tissues and prevent toxicity. Recently, there has been increasing interest in magnesium as a biomaterial: it is the fourth most abundant cation in the human body, and it is essential for human metabolism. However magnesium nanoparticles (Mg NPs) have had limited diffusion due to the high reduction potential of magnesium cations, which makes NPs synthesis challenging. Herein, we report the synthesis of Mg NPs and their surface functionalization for the obtainment of a stable and biocompatible nanomaterial suitable for photothermal ablation therapy against cancer. We synthesized the Mg crystals by reducing MgCl2 with metallic lithium and exploiting naphthalene as an electron carrier: the lithium–naphthalene complex acts as the real reducing agent. Firstly, the nanocrystal particles were coated with the ligand 12-ethoxy ester dodecanehydroxamic acid, and then entrapped into water-dispersible polymeric micelles (PMs) made of the FDA-approved PLGA-b-PEG-COOH copolymer using the oil-in-water emulsion technique. Lately, we developed a more straightforward methodology by introducing chitosan, a highly biocompatible natural product, at the beginning of the process, simultaneously using lithium–naphthalene complex, thus having a one-pot procedure for the formation and surface modification of MgNPs. The obtained MgNPs were purified and fully characterized, showing diameters in the range of 50-300 nm. Notably, when coated with chitosan the particles remained stable as dry powder for more than 10 months. We proved the possibility of generating a temperature rise of a few to several degrees once MgNPs were illuminated using a 810 nm diode laser operating in continuous wave mode: the temperature rise resulted significant (0-15 °C) and concentration dependent. We then investigated potential cytotoxicity of the MgNPs: we used HN13 epithelial cells, derived from a head and neck squamous cell carcinoma and the hepa1-6 cell line, derived from hepatocellular carcinoma and very low toxicity was observed for both nanosystems. Finally, in vivo photothermal therapy was performed on xenograft hepa1-6 tumor bearing mice: the animals were treated with MgNPs coated with chitosan and showed no sign of suffering after the injection. After 12 hours the tumor was exposed to near-infrared laser light. The results clearly showed an extensive damage to tumor tissue after only 2 minutes of laser irradiation at 3Wcm-1, while no damage was reported when the tumor was treated with the laser and saline alone in control group. Despite the lower photothermal efficiency of Mg with respect to Au NPs, we consider MgNPs a promising, safe and green candidate for future clinical translations.

Keywords: chitosan, magnesium nanoparticles, nanomedicine, photothermal therapy

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Authors: Jonny Beirne

Abstract:

Hydropower developments have come to assume an important role within the Ethiopian government's overall development strategy for the country during the last ten years. The Gilgel Gibe III on the Omo river, due to become operational in September 2014, represents the most ambitious, and controversial, of these projects to date. Further aspects of the government's national development strategy include leasing vast areas of designated 'unused' land for large-scale commercial agricultural projects and 'voluntarily' villagizing scattered, semi-nomadic agro-pastoralist groups to centralized settlements so as to use land and water more efficiently and to better provide essential social services such as education and healthcare. The Lower Omo valley, along the Omo River, is one of the sites of this villagization programme as well as of these large-scale commercial agricultural projects which are made possible owing to the regulation of the river's flow by Gibe III. Though the Ethiopian government cite many positive aspects of these agricultural and hydropower developments there are still expected to be serious regional and transnational effects, including on migration flows, in an area already characterized by increasing climatic vulnerability with attendant population movements and conflicts over scarce resources. The following paper is an attempt to track actual and anticipated migration flows resulting from the construction of Gibe III in the immediate vicinity of the dam, downstream in the Lower Omo Valley and across the border in Kenya around Lake Turkana. In the case of those displaced in the Lower Omo Valley, this will be considered in view of the distinction between voluntary villagization and forced resettlement. The research presented is not primary-source material. Instead, it is drawn from the reports and assessments of the Ethiopian government, rights-based groups, and academic researchers as well as media articles. It is hoped that this will serve to draw greater attention to the issue and encourage further methodological research on the dynamics of dam constructions (and associated large-scale irrigation schemes) on migration flows and on the ultimate experience of displacement and resettlement for environmental migrants in the region.

Keywords: forced displacement, voluntary resettlement, migration, human rights, human security, land grabs, dams, commercial agriculture, pastoralism, ecosystem modification, natural resource conflict, livelihoods, development

Procedia PDF Downloads 358

Authors: Adebisi Adunola Demehin, Wanlaya Thamnarak, Jaruwan Chatwichien, Chatchakorn Eurtivong, Kiattawee Choowongkomon, Somsak Ruchirawat, Nopporn Thasana

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The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein involved in cellular signalling processes and, its aberrant activity is crucial in the development of many cancers such as lung cancer. Selaginellaceae are fern allies that have long been used in Chinese traditional medicine to treat various cancer types, especially lung cancer. Biflavonoids, the major secondary metabolites in Selaginellaceae, have numerous pharmacological activities, including anti-cancer and anti-inflammatory. For instance, amentoflavone induces a cytotoxic effect in the human NSCLC cell line via the inhibition of PARP-1. However, to the best of our knowledge, there are no studies on biflavonoids as EGFR inhibitors. Thus, this study aims to investigate the EGFR inhibitory activities of biflavonoids isolated from Selaginella siamensis and Selaginella bryopteris. Amentoflavone, tetrahydroamentoflavone, sciadopitysin, robustaflavone, robustaflavone-4-methylether, delicaflavone, and chrysocauloflavone were isolated from the ethyl-acetate extract of the whole plants. The structures were determined using NMR spectroscopy and mass spectrometry. In vitro study was conducted to evaluate their cytotoxicity against A549, HEPG2, and T47D human cancer cell lines using the MTT assay. In addition, a target-based assay was performed to investigate their EGFR inhibitory activity using the kinase inhibition assay. Finally, a molecular docking study was conducted to predict the binding modes of the compounds. Robustaflavone-4-methylether and delicaflavone showed the best cytotoxic activity on all the cell lines with IC50 (µM) values of 18.9 ± 2.1 and 22.7 ± 3.3 on A549, respectively. Of these biflavonoids, delicaflavone showed the most potent EGFR inhibitory activity with an 84% relative inhibition at 0.02 nM using erlotinib as a positive control. Robustaflavone-4-methylether showed a 78% inhibition at 0.15 nM. The docking scores obtained from the molecular docking study correlated with the kinase inhibition assay. Robustaflavone-4-methylether and delicaflavone had a docking score of 72.0 and 86.5, respectively. The inhibitory activity of delicaflavone seemed to be linked with the C2”=C3” and 3-O-4”’ linkage pattern. Thus, this study suggests that the structural features of these compounds could serve as a basis for developing new EGFR-TK inhibitors.

Keywords: anticancer, biflavonoids, EGFR, molecular docking, Selaginellaceae

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