Search results for: creep mechanisms

Authors: Mpho Mokoatle, Darlington Mapiye, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

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Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on $k$-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0%, 80.5%, 80.5%, 63.6%, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms.

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

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Authors: Darlington Mapiye, Mpho Mokoatle, James Mashiyane, Stephanie Muller, Gciniwe Dlamini

Abstract:

Great advances in high-throughput sequencing technologies have resulted in availability of huge amounts of sequencing data in public and private repositories, enabling a holistic understanding of complex biological phenomena. Sequence data are used for a wide range of applications such as gene annotations, expression studies, personalized treatment and precision medicine. However, this rapid growth in sequence data poses a great challenge which calls for novel data processing and analytic methods, as well as huge computing resources. In this work, a machine and statistical learning approach for DNA sequence classification based on k-mer representation of sequence data is proposed. The approach is tested using whole genome sequences of Mycobacterium tuberculosis (MTB) isolates to (i) reduce the size of genomic sequence data, (ii) identify an optimum size of k-mers and utilize it to build classification models, (iii) predict the phenotype from whole genome sequence data of a given bacterial isolate, and (iv) demonstrate computing challenges associated with the analysis of whole genome sequence data in producing interpretable and explainable insights. The classification models were trained on 104 whole genome sequences of MTB isoloates. Cluster analysis showed that k-mers maybe used to discriminate phenotypes and the discrimination becomes more concise as the size of k-mers increase. The best performing classification model had a k-mer size of 10 (longest k-mer) an accuracy, recall, precision, specificity, and Matthews Correlation coeffient of 72.0 %, 80.5 %, 80.5 %, 63.6 %, and 0.4 respectively. This study provides a comprehensive approach for resampling whole genome sequencing data, objectively selecting a k-mer size, and performing classification for phenotype prediction. The analysis also highlights the importance of increasing the k-mer size to produce more biological explainable results, which brings to the fore the interplay that exists amongst accuracy, computing resources and explainability of classification results. However, the analysis provides a new way to elucidate genetic information from genomic data, and identify phenotype relationships which are important especially in explaining complex biological mechanisms

Keywords: AWD-LSTM, bootstrapping, k-mers, next generation sequencing

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Authors: Jung Lee, L. G. Pee

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The 'Like' function in social media platforms represents the immediate responses of social media users to postings and other users. A large number of 'likes' is often attributed to fame, agreement, and support from others that many users are proud of and happy with. However, what 'like' implies exactly in social media context is still in discussion. Some argue that it is an accurate parameter of the preferences of social media users, whereas others refute that it is merely an instant reaction that is volatile and vague. To address this gap, this study investigates how social media users perceive the 'like' function and behave differently based on their perceptions. This study posits the following arguments. First, 'like' is interpreted as a quantified form of social capital that resides in social media platforms. This incarnated social capital rationalizes the attraction of people to social media and belief that social media platforms bring benefits to their relationships with others. This social capital is then conceptualized into cognitive and emotive dimensions, where social capital in the cognitive dimension represents the awareness of the 'likes' quantitatively, whereas social capital in the emotive dimension represents the receptions of the 'likes' qualitatively. Finally, the ambivalent perspective of the social media users on 'like' (i.e., social capital) is applied. This view rationalizes why social media users appreciate the reception of 'likes' from others but are aware that those 'likes' can distort the actual responses of other users by sending erroneous signals. The rationale on this ambivalence is based on whether users perceive social media as private or public spheres. When social media is more publicized, the ambivalence is more strongly observed. By combining the ambivalence and dimensionalities of the social capital, four types of social media users with different mechanisms on liking behaviors are identified. To validate this work, a survey with 300 social media users is conducted. The analysis results support most of the hypotheses and confirm that people have ambivalent perceptions on 'like' as a social capital and that perceptions influence behavioral patterns. The implication of the study is clear. First, this study explains why social media users exhibit different behaviors toward 'likes' in social media. Although most of the people believe that the number of 'likes' is the simplest and most frank measure of supports from other social media users, this study introduces the users who do not trust the 'likes' as a stable and reliable parameter of social media. In addition, this study links the concept of social media openness to explain the different behaviors of social media users. Social media openness has theoretical significance because it defines the psychological boundaries of social media from the perspective of users.

Keywords: ambivalent attitude, like function, social capital, social media

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Authors: Saeed Anwar

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Foreign aid has long been a prominent tool in the pursuit of economic development in recipient countries. This research paper aims to analyze the impact of foreign aid on economic development and explore the effectiveness of aid in promoting sustainable growth, poverty reduction, and improvements in human development indicators. Drawing upon a comprehensive review of existing literature, both theoretical frameworks and empirical evidence are synthesized to provide insights into the complex relationship between foreign aid and economic development. The paper examines various channels through which foreign aid influences economic development, including infrastructure development, education and healthcare investments, technology transfer, and institutional capacity building. It explores the potential positive effects of aid in stimulating economic growth, reducing poverty, and enhancing human capital formation. Additionally, it investigates the potential challenges and limitations associated with aid, such as aid dependency, governance issues, and the potential crowding out of domestic resources. Furthermore, the study assesses the heterogeneity of aid effectiveness across different types of aid modalities, recipient country characteristics, and aid allocation mechanisms. It considers the role of aid conditionality, aid fragmentation, and aid targeting in influencing the effectiveness of aid in promoting economic development. The findings of this research contribute to the ongoing discourse on foreign aid and economic development by providing a comprehensive analysis of the existing literature. The study highlights the importance of context-specific factors, recipient country policies, and aid effectiveness frameworks in determining the impact of foreign aid on economic development outcomes. The insights derived from this research can inform policymakers, donor agencies, and practitioners in designing and implementing effective aid strategies to maximize the positive impact of foreign aid on economic development.

Keywords: foreign aid, economic development, sustainable growth, poverty reduction, human development indicators, infrastructure development, education, healthcare, technology transfer, institutional capacity building, aid effectiveness, aid dependency, governance, crowding out, aid conditionality, aid fragmentation, aid targeting, recipient country policies, aid strategies, donor agencies, policymaking

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Authors: Xi Wang, Yoshio Bando

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Lithium-ion batteries (LIBs) can deliver high levels of energy storage density and offer long operating lifetimes, but their power density is too low for many important applications. Therefore, we developed some new strategies and fabricated novel electrodes for fast Li transport and its facile synthesis including N-doped graphene-SnO2 sandwich papers, bicontinuous nanoporous Cu/Li4Ti5O12 electrode, and binder-free N-doped graphene papers. In addition, by using advanced in-TEM, STEM techniques and the theoretical simulations, we systematically studied and understood their storage mechanisms at the atomic scale, which shed a new light on the reasons of the ultrafast lithium storage property and high capacity for these advanced anodes. For example, by using advanced in-situ TEM, we directly investigated these processes using an individual CuO nanowire anode and constructed a LIB prototype within a TEM. Being promising candidates for anodes in lithium-ion batteries (LIBs), transition metal oxide anodes utilizing the so-called conversion mechanism principle typically suffer from the severe capacity fading during the 1st cycle of lithiation–delithiation. Also we report on the atomistic insights of the GN energy storage as revealed by in situ TEM. The lithiation process on edges and basal planes is directly visualized, the pyrrolic N "hole" defect and the perturbed solid-electrolyte-interface (SEI) configurations are observed, and charge transfer states for three N-existing forms are also investigated. In situ HRTEM experiments together with theoretical calculations provide a solid evidence that enlarged edge {0001} spacings and surface "hole" defects result in improved surface capacitive effects and thus high rate capability and the high capacity is owing to short-distance orderings at the edges during discharging and numerous surface defects; the phenomena cannot be understood previously by standard electron or X-ray diffraction analyses.

Keywords: in-situ TEM, STEM, advanced anode, lithium-ion batteries, storage mechanism

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Authors: P. Annapurna, Cecil Ross, Sudhir Krishna, Sweta Srivastava

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Irradiation plays a pivotal role in cervical cancer treatment, however some tumors exhibit resistance to therapy while some exhibit relapse, due to better repair and enhanced resistance mechanisms operational in their cells. The present study aims to understand the signaling mechanism operational in resistance phenotype and in the present study we report the role of Rho GTPase associated protein kinase (ROCK) signaling in cervical carcinoma radio-resistance. ROCK signaling has been implicated in several tumor progressions and is important for DNA repair. Irradiation of spheroid cultures of SiHa cervical carcinoma derived cell line at 6Gy resulted in generation of resistant cells in vitro which had better clonogenic abilities and formed larger and more colonies, in soft agar colony formation assay, as compared to the non-irradiated cells. These cells also exhibited an enhanced motility phenotype. Cell cycle profiling showed the cells to be blocked in G2M phase with enhanced pCDC2 levels indicating onset of possible DNA repair mechanism. Notably, 3 days post-irradiation, irradiated cells showed increased ROCK2 translocation to the nucleus with enhanced protein expression as compared to the non-irradiated cells. Radio-sensitization of the resistant cells was enhanced using Y27632, an inhibitor to ROCK signaling. The treatment of resistant cells with Y27632 resulted in increased cell death upon further irradiation. This observation has been confirmed using inhibitory antibodies to ROCK1/2. Result show that both ROCK1/2 have a functional contribution in radiation resistance of cervical cancer cells derived from cell lines. Interestingly enrichment of stem like cells (Hoechst negative cells) was also observed upon irradiation and these cells were markedly sensitive to Y27632 treatment. Our results thus suggest the role of ROCK signaling in radio-resistance in cervical carcinoma. Further studies with human biopsies, mice models and mechanistic of ROCK signaling in the context of radio-resistance will clarify the role of this molecule further and allow for therapeutics development.

Keywords: cervical carcinoma, radio-resistance, ROCK signaling, cancer treatment

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Authors: Wendy de Gomez

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Standardization is a critical element in the ability of a society to reduce uncertainty, subjectivity, misrepresentation, and interpretation while simultaneously contributing to innovation. Technological standardization is critical to codify specific operationalization through legal instruments that provide rules of development, expectation, and use. In the current emerging technology landscape Artificial Intelligence (AI) hardware as a general use technology has seen incredible growth as evidenced from AI technology patents between 2012 and 2018 in the United States Patent Trademark Office (USPTO) AI dataset. However, as outlined in the 2023 United States Government National Standards Strategy for Critical and Emerging Technology the codification through standardization of emerging technologies such as AI has not kept pace with its actual technological proliferation. This gap has the potential to cause significant divergent possibilities for the downstream outcomes of AI in both the short and long term. This original empirical research provides an overview of the standardization efforts around AI in different geographies and provides a background to standardization law. It quantifies the longitudinal trend of Artificial Intelligence hardware patents through the USPTO AI dataset. It seeks evidence of existing Standard Essential Patents from these AI hardware patents through a text analysis of the Statement of patent history and the Field of the invention of these patents in Patent Vector and examines their determination as a Standard Essential Patent and their inclusion in existing AI technology standards across the four main AI standards bodies- European Telecommunications Standards Institute (ETSI); International Telecommunication Union (ITU)/ Telecommunication Standardization Sector (-T); Institute of Electrical and Electronics Engineers (IEEE); and the International Organization for Standardization (ISO). Once the analysis is complete the paper will discuss both the theoretical and operational implications of F/Rand Licensing Agreements for the owners of these Standard Essential Patents in the United States Court and Administrative system. It will conclude with an evaluation of how Standard Setting Organizations (SSOs) can work with SEP owners more effectively through various forms of Intellectual Property mechanisms such as patent pools.

Keywords: patents, artifical intelligence, standards, F/Rand agreements

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Authors: Ana Lambelho

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Nowadays is very common that an activity may be performed independently or dependently. In Portugal, the Labour Law exclusively protects the dependent labour relations. The independent work is regulated by civil law, where the autonomy of the will is the main principle. For companies is more advantageous to hire people under a service agreement since, in that case, the relation is not submitted to the limits established in Labour law and collective bargaining. This practice has nothing wrong, if the performance of work is, in fact, made autonomously. The problem is the increased frequency of the celebration of service agreements to hide a legal relation of subordination. Aware of this and regarding the huge difficulty to demonstrate the existence of subordinated work (that often runs against the employee), the Portuguese legislator devoted some legislative rules in order to facilitate the evidence of legal subordination and, on the other hand, to avoid the misuse of the provision of service agreements. This study focuses precisely on the analysis of this solution, namely the so-called presumption of ‘laboralidade’ and on the lawsuit to recognize the existence of a labour contract. The presumption of the existence of a labour contract is present in the Portuguese legal system since 2003, and received, with the 2009 Labour Code, a new redaction that, according to the doctrine and the jurisprudence, finally approached it to a legal presumption, with the consequent reversal of the burden of proof and, in consequence, made easier to proof the legal subordination, because the employee will just have to plead and prove the existence of two of the elements described in the law to use this presumption. Another change in the Portuguese legal framework is related with the competencies of the Authority for Working Conditions (AWC): now, if during an inspection, the Authority finds a situation that seems to be an undeclared employment situation, it may access the company and, if it does not regularize voluntarily the situation, AWC has a duty to communicate to the public prosecutor, who will begin the lawsuit for the recognition of the existence of an employment contract. To defend the public interest, the action to recognize the existence of an employment contract will follow its terms, even against the employee will. Although the existence of these mechanisms does not solve by itself the problem of evasion of labour law and false ‘green receipts’, it is undeniable that it is an important step in combating fraud in this field.

Keywords: independent work, labour contract, Portugal, service agreement

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Authors: Mahdokht Sadeghvishkaei, Azizah Abdul-Hamid, Amin Ismail, Nazamid Saari

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Hypertension is a common and serious chronic health problem and known as the most important risk factor for development of many diseases such as stroke. Since angiotensin I-converting enzyme (ACE) is the key enzyme involved in blood pressure, one of the well accepted mechanisms to control hypertension is through ACE inhibition. The ACE inhibitory effect of Actinopyga lecanora (stone fish) proteolysate in vitro had been reported. Hence, this study aimed to evaluate the ACE inhibitory potential of Actinopyga lecanora proteolysate in vivo in normotensive rats. Therefore the ACE inhibitory capability of the proteolysate to prevent increasing systolic blood pressure, after inducing hypertension by angiotensin I was examined. The pre-fed rats with the proteolysates at various doses (200, 400, 800 mg/kg body weight) revealed the significant (p ≤ 0.05) suppression effect compared with control groups. Furthermore, different doses of the proteolysate (200, 400, 800 mg/kg body weight) were examined to find its optimum effective dose. Results depicted that 800 mg proteolysate/kg body weight significantly reduced systolic blood pressure without negative effect on normal blood pressure (p ≤ 0.05). Furthermore, Sub-acute toxicity study based on OECD guideline demonstrated the safety of the proteolysate in vivo. The present study indicated that the proteolysate at a dose of 1000 mg/kg daily for 14 days did not cause toxicity signs such as death, changes in activity, or piloerection. Since there are no significant differences between treated groups and control groups, hematological and biochemical analysis confirmed safety of the proteolysate (p > 0.05). In addition, there were no significant differences between organs weights of the treated groups and the control groups. Morphologically, neither histopathological changes, nor gross abnormalities were observed. However, the proteolysate caused significant decrease in body weight in relation to the control groups (p ≤ 0.05) probably due to appetite stimulation by the proteolysate, leading to decreased food consumption in sub-acute group. It is concluded that the proteolysate generated from Actinopyga lecanora possess a significant anti-hypertensive effect and would be potentially used as natural alternative of ACE inhibitors.

Keywords: ACE inhibition, Actinopyga lecanora, anti-hypertensive activity, bioactive peptides, normotensive rats

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Authors: Tarek Elnimr, Reda Morsy, Assem El Fert, Aziza Ismail

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Hepatitis is an inflammation of the liver. The condition can be self-limiting or can progress to fibrosis, cirrhosis or liver cancer. Disease caused by the hepatitis virus, the virus can cause hepatitis infection, ranging in severity from a mild illness lasting a few weeks to a serious, lifelong illness. A growing body of evidence indicates that many trace elements play important roles in a number of carcinogenic processes that proceed with various mechanisms. To examine the status of trace elements during the development of hepatic carcinoma, we determined the iron, copper, zinc and selenium levels in some biological samples of patients at different stages of viral hepatic disease. We observed significant changes in the iron, copper, zinc and selenium levels in the biological samples of patients hepatocellular carcinoma, relative to those of healthy controls. The mean hair, nail, RBC, serum and whole blood copper levels in patients with hepatitis virus were significantly higher than that of the control group. In contrast the mean iron, zinc, and selenium levels in patients having hepatitis virus were significantly lower than those of the control group. On the basis of this study, we identified the impact of natural supplements to improve the treatment of viral liver damage, using the level of some trace elements such as, iron, copper, zinc and selenium, which might serve as biomarkers for increases survival and reduces disease progression. Most of the elements revealed diverse and random distribution in the samples of the donor groups. The correlation study pointed out significant disparities in the mutual relationships among the trace elements in the patients and controls. Principal component analysis and cluster analysis of the element data manifested diverse apportionment of the selected elements in the scalp hair, nail and blood components of the patients compared with the healthy counterparts.

Keywords: hepatitis, hair, nail, blood components, trace element, nutrition therapy, multivariate analysis, correlation, ICP-MS

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Authors: Reda A. Elkhyat, Mahmoud Nasr, Amel A. Tammam, Mohamed A. Ghazy

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Pharmaceuticals and personal care products (PPCPs) are a unique group of emerging contaminants continuously introduced into the aquatic ecosystem at concentrations capable of inducing adverse effects on humans and aquatic organisms, even at trace levels ranging from ppt to ppm. Amongst the common pharmaceutical emerging pollutants detected in several aquatic environments, acetaminophen has been recognized for its high toxicity. Once released into the aquatic environment, acetaminophen could be degraded by the microbial community and adsorption/ uptake by the plants. Although many studies have investigated the hazard risks of acetaminophen pollutants on aquatic animals, the number of studies demonstrating its removal efficiency and effects on the aquatic plant still needs to be expanded. In this context, this study aims to apply the aquatic plant-based phytoremediation system to eliminate this emerging contaminant from domestic wastewater. The phytoremediation experiment was performed in a hydroponic system containing Eichhornia crassipes and operated under the natural environment at 25°C to 30°C. This system was subjected to synthetic domestic wastewater with the maximum initial chemical oxygen demand (COD) of 390 mg/L and three different acetaminophen concentrations of 25, 50, and 200 mg/L. After 17 d of operation, the phytoremediation system achieved removal efficiencies of about 100% and 85.6±4.2% for acetaminophen and COD, respectively.Moreover, the Eichhornia crassipes could withstand the toxicity associated with increasing the acetaminophen concentrations from 25 to 200 mg/L. This high treatment performance could be assigned to the well-adaptation of the water hyacinth to the phytoremediation factors. Moreover, it has been proposed that this phytoremediation system could be largely supported by phytodegradation and plant uptaking mechanisms; however, detecting the generated intermediates, metabolites, and degradation products are still under investigation. Applying this free-floating plant in wastewater treatment and reducing emerging contaminants would meet the targets of SDGs 3, 6, and. 14. The cost-benefit analysis was performed for the phytoremediation system. The phytoremediation system is financially viable as the net profit was 2921 US $/ y with a payback period of nine years.

Keywords: domestic wastewater, emerging pollutants, hydrophyte Eichhornia crassipes, paracetamol removal efficiency, sustainable development goals (SDGs)

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Authors: K. Akutsu, S. Mori, T. Hanashima

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Fluorescent probes are useful for the selective detection of trace amount of ions and biomolecular imaging in living cells. Various kinds of metal ion-selective fluorescent compounds have been developed, and some compounds have been applied as effective metal ion-selective fluorescent probes. However, because competition between the ligand and water molecules for the metal ion constitutes a major contribution to the stability of a complex in aqueous solution, it is difficult to develop a highly sensitive, selective, and stable fluorescent probe in aqueous solution. The micelles, these are formed in the surfactant aqueous solution, provides a unique hydrophobic nano-environment for stabilizing metal-organic complexes in aqueous solution. Therefore, we focused on the unique properties of micelles to develop a new fluorescence analysis system. We have been developed a fluorescence analysis system for Sr(II) by using a Sr(II) fluorescent sensor, N-(2-hydroxy-3-(1H-benzimidazol-2-yl)-phenyl)-1-aza-18-crown-6-ether (BIC), and studied its complexation behavior with Sr(II) in micellar solution. We revealed that the stability constant of Sr(II)-BIC complex was 10 times higher than that in aqueous solution. In addition, its detection limit value was also improved up to 300 times by this system. However, the mechanisms of these phenomena have remained obscure. In this study, we investigated the structure of Sr(II)-BIC complex in aqueous micellar solution by combining use the extended X-ray absorption fine structure (EXAFS) and neutron reflectivity (NR) method to understand the unique properties of the fluorescence analysis system from the view point of structural chemistry. EXAFS and NR experiments were performed on BL-27B at KEK-PF and on BL17 SHARAKU at J-PARC MLF, respectively. The obtained EXAFS spectra and their fitting results indicated that Sr(II) and BIC formed a Sr(18-crown-6-ether)-like complex in aqueous micellar solution. The EXAFS results also indicated that the hydrophilic head group of surfactant molecule was directly coordinated with Sr(II). In addition, the NR results also indicated that Sr(II)-BIC complex would interact with the surface of micelle molecules. Therefore, we concluded that Sr(II), BIC, and surfactant molecule formed a ternary complexes in aqueous micellar solution, and at least, it is clear that the improvement of the stability constant in micellar solution is attributed to the result of the formation of Sr(BIC)(surfactant) complex.

Keywords: micell, fluorescent probe, neutron reflectivity, EXAFS

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Authors: Islam Nowisser, Noha Farag, Mohamed El Azizi

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Helicobacter pylori is a highly important human pathogen which inhabits about 50% of the population worldwide. Infection with this bacteria is very hard to treat, with high probability of recurrence. H. pylori causes severe gastric diseases, including peptic ulcer, gastritis, and gastric cancer, which has been linked to chronic inflammation. The infection has been reported to be associated with high levels of pro-inflammatory cytokines, especially IL-1β and TNF-α. The aim of the current study is to investigate the molecular mechanisms by which H. pylori activates NLRP3 inflammasome and its contribution to Il-1 β production in an innate cellular model. H. pylori PMSS1 and G27 standard strains, as well as the PMSS1 isogenic mutant strain PMSS1ΔVacA and G27ΔVacA, G27ΔCagA in addition to clinical isolates obtained from biopsy samples from the antrum and corpus mucosa of chronic gastritis patients, were used to establish infection in RAW-264.7 macrophages. The production levels of TNF-α and IL-1β was assessed using ELISA. Since expression of these cytokines is often regulated by the transcription factor complex, nuclear factor-kB (NF-kB), the activation of NF-κB in H. pylori infected cells was also evaluated by luciferase assay. Genomic DNA was extracted from bacterial cultures of H. pylori clinical isolates as well as the standard strains and their corresponding mutants, where they were evaluated for the cagA pathogenicity island and vacA expression. The correlation between these findings and expression of the cagA Pathogenicity Island and vacA in the bacteria was also investigated. The results showed IL-1β, and TNF-α production significantly increased in raw macrophages following H. pylori infection. The cagA+ and vacA+ H. pylori strains induced significant production of IL-1β compared to cagA- and vacA- strains. The activation pattern of NF-κB was correlated in the isolates to their cagA and vacA expression profiles. A similar finding could not be confirmed for TNF-α production. Our study shows the ability of H. pylori to activate NF-kB and induce significant IL-1β production as a possible mechanism for the augmented inflammatory response seen in subjects infected with cagA+ and vacA+ H. pylori strains that would lead to the progression to more severe form of the disease.

Keywords: Helicobacter pylori, IL-1β, inflammatory cytokines, nuclear factor KB, TNF-α

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Authors: Hasna Elalaoui Elabdallaoui, Abdelaziz Elfazziki, Mohamed Sadgal

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Outlines: The social economy is a moral approach to solidarity applied to the projects’ development. To reconcile economic activity and social equity, crowdfunding is as an alternative means of financing social projects. Several collaborative blockchain platforms exist. It eliminates the need for a central authority or an inconsiderate middleman. Also, the costs for a successful crowdfunding campaign are reduced, since there is no commission to be paid to the intermediary. It improves the transparency of record keeping and delegates authority to authorities who may be prone to corruption. Objectives: The objectives are: to define a software infrastructure for projects’ participatory financing within a social and solidarity economy, allowing transparent, secure, and fair management and to have a financial mechanism that improves financial inclusion. Methodology: The proposed methodology is: crowdfunding platforms literature review, financing mechanisms literature review, requirements analysis and project definition, a business plan, Platform development process and implementation technology, and testing an MVP. Contributions: The solution consists of proposing a new approach to crowdfunding based on Islamic financing, which is the principle of Mousharaka inspired by Islamic financing, which presents a financial innovation that integrates ethics and the social dimension into contemporary banking practices. Conclusion: Crowdfunding platforms need to secure projects and allow only quality projects but also offer a wide range of options to funders. Thus, a framework based on blockchain technology and Islamic financing is proposed to manage this arbitration between quality and quantity of options. The proposed financing system, "Musharaka", is a mode of financing that prohibits interests and uncertainties. The implementation is offered on the secure Ethereum platform as investors sign and initiate transactions for contributions using their digital signature wallet managed by a cryptography algorithm and smart contracts. Our proposal is illustrated by a crop irrigation project in the Marrakech region.

Keywords: social economy, Musharaka, blockchain, smart contract, crowdfunding

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Authors: Esam Jassim

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Industries using conventional fossil fuels have an interest in better understanding the mechanism of particulate formation during combustion since such is responsible for emission of undesired inorganic elements that directly impact the atmospheric pollution level. Fine and ultrafine particulates have tendency to escape the flue gas cleaning devices to the atmosphere. They also preferentially collect on surfaces in power systems resulting in ascending in corrosion inclination, descending in the heat transfer thermal unit, and severe impact on human health. This adverseness manifests particularly in the regions of world where coal is the dominated source of energy for consumption. This study highlights the behavior of calcium transformation as mineral grains verses organically associated inorganic components during pulverized coal combustion. The influence of existing type of calcium on the coarse, fine and ultrafine mode formation mechanisms is also presented. The impact of two sub-bituminous coals on particle size and calcium composition evolution during combustion is to be assessed. Three mixed blends named Blends 1, 2, and 3 are selected according to the ration of coal A to coal B by weight. Calcium percentage in original coal increases as going from Blend 1 to 3. A mathematical model and a new approach of describing constituent distribution are proposed. Analysis of experiments of calcium distribution in ash is also modeled using Poisson distribution. A novel parameter, called elemental index λ, is introduced as a measuring factor of element distribution. Results show that calcium in ash that originally in coal as mineral grains has index of 17, whereas organically associated calcium transformed to fly ash shown to be best described when elemental index λ is 7. As an alkaline-earth element, calcium is considered the fundamental element responsible for boiler deficiency since it is the major player in the mechanism of ash slagging process. The mechanism of particle size distribution and mineral species of ash particles are presented using CCSEM and size-segregated ash characteristics. Conclusions are drawn from the analysis of pulverized coal ash generated from a utility-scale boiler.

Keywords: coal combustion, inorganic element, calcium evolution, fluid dynamics

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Authors: Cindy Woods

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After years of implacable neoliberal globalization, multinational corporations have moved from the periphery to the center of the international legal agenda. Human rights advocates have long called for greater corporate accountability in the international arena. The creation of the Global Compact in 2000, while aimed at fostering greater corporate respect for human rights, did not silence these calls. After multiple unsuccessful attempts to adopt a set of norms relating to the human rights responsibilities of transnational corporations, the United Nations succeeded in 2008 with the Guiding Principles on Business and Human Rights (Guiding Principles). The Guiding Principles, praised by some within the international human rights community for their recognition of an individual corporate responsibility to respect human rights, have not escaped their share of criticism. Many view the Guiding Principles to be toothless, failing to directly impose obligations upon corporations, and call for binding international obligations on corporate entities. After decades of attempting to promulgate human rights obligations for multinational corporations, the existing legal frameworks in place fall short of protecting individuals from the human rights abuses of multinational corporations. The Global Compact and Guiding Principles are proof of the United Nations’ unwillingness to impose international legal obligations on corporate actors. In June 2014, the Human Rights Council adopted a resolution to draft international legally binding human rights norms for business entities; however, key players in the international arena have already announced they will not cooperate with such efforts. This Note, through an overview of the existing corporate accountability frameworks and a study of Newmont Mining’s Minas Conga project in Peru, argues that binding international human rights obligations on corporations are necessary to fully protect human rights. Where states refuse to or simply cannot uphold their duty to protect individuals from transnational businesses’ human rights transgressions, there must exist mechanisms to pursue justice directly against the multinational corporation.

Keywords: business and human rights, Latin America, international treaty on business and human rights, mining, human rights

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Authors: Raquel Vianna Duarte Cardoso, Eduarda Lobato Faria, José Jorge Boueri

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Rapid urbanization has transformed the global landscape, presenting significant challenges to public health. This article delves into the impact of urbanization on the spread of infectious diseases in cities and identifies crucial strategies to enhance urban community resilience. Massive urbanization over recent decades has created conducive environments for the rapid spread of diseases due to population density, mobility, and unequal living conditions. Urbanization has been observed to increase exposure to pathogens and foster conditions conducive to disease outbreaks, including seasonal flu, vector-borne diseases, and respiratory infections. In order to tackle these issues, a range of cross-disciplinary approaches are suggested. These encompass the enhancement of urban healthcare infrastructure, emphasizing the need for robust investments in hospitals, clinics, and healthcare systems to keep pace with the burgeoning healthcare requirements in urban environments. Moreover, the establishment of disease monitoring and surveillance mechanisms is indispensable, as it allows for the timely detection of outbreaks, enabling swift responses. Additionally, community engagement and education play a pivotal role in advocating for personal hygiene, vaccination, and preventive measures, thus playing a pivotal role in diminishing disease transmission. Lastly, the promotion of sustainable urban planning, which includes the creation of cities with green spaces, access to clean water, and proper sanitation, can significantly mitigate the risks associated with waterborne and vector-borne diseases. The article is based on a review of scientific literature, and it offers a comprehensive insight into the complexities of the relationship between urbanization and health. It places a strong emphasis on the urgent need for integrated approaches to improve urban resilience in the face of health challenges.

Keywords: infectious diseases dissemination, public health, urbanization impacts, urban resilience

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Authors: Folayele Oluyemi Akindeju, Tobi Joseph Ajoro

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The city as a complex system exhibiting chaotic behaviour is in a state of constant change, in response to prevailing social, economic, environmental and technological factors. Without adequate investigation and control mechanisms to tame the sporadic nature of growth in most urban areas of cities in developing regions, organic sprawling visibly manifests with its attendant problems, most especially at peri-urban areas. The Lagos Megacity region in southwest Nigeria, as one of the largest megacities in the world contends with the challenges of sprawling at the peri-urban areas especially along emerging transit corridors. Due to the seemingly unpredictable nature of this growth, this paper attempts a morphological investigation into the growth of peri-urban settlements along the Mowe-Ibafo transit corridor of the Megacity region over a temporal space of three decades (1984-2014). This study adopts the application of the Fractal Analysis and Regression Analysis methods through the correlation of population density and fractal dimension values to establish the pattern and nature of growth, due to the inadequacies of conventional methods of urban analysis which cannot deal with the unpredictability of such complex urban forms as the peri-urban areas. It was deduced that the dynamic urban expansion in the last three decades resulted in about 74.2% urban change rate between 1984 and 2000 and 63.4% urban change rate between 2000 and 2014. With the R2 value between the fractal dimension and population density been 1, the regression model indicates a positive correlation between Fractal Dimension (D) and Population Density (pop/km2), where the increase in the population density from 5740 pop/km2 to 8060 pop/km2 and later decrease to 7580 pop/km2 leads to an increase in the fractal dimension of urban growth from 1.451 in 1984 to 1.853 in 2014. This, therefore, justifies the ability to predict and determine the nature and direction of growth of complex entities and is sufficient to substantially suggest the need for adequate policy framework towards sustainable urban planning and infrastructural provision in the Peri-urban areas.

Keywords: fractal analysis, Lagos Megacity, peri-urban, sprawling, urban morphology

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Authors: M. Achemo, O. Saito

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Jefoure land use system is one of the traditional landscape human settlement patterns, and it is a cultural design and peculiar art of the people of Gurage in Ethiopia via which houses and trees flank roads left and right. Assessment of the multiple benefits of the traditional road that benefit society and development could enhance the understanding of the land use planners and decision makers to pay attention while planning and managing the land use system. Recent trend shows that the Jefoure land use is on the threshold of change as a result of flourishing road networks, overgrazing, and agricultural expansion. This study aimed to evaluate the multiple ecosystem services provided by the Jefoure land use system after characterization of the socio-ecological landscape. Information was compiled from existing data sources such as ordnance survey maps, aerial photographs, recent high resolution satellite imageries, designated questionnaires and interviews, and local authority contacts. The result generated scientific data on the characteristics, ecosystem services provision, and drivers of changes. The cultural landscape has novel characteristics and providing multiple ecosystem services to the community for long period of time. It is serving as road for humans, livestock and vehicles, habitat for plant species, regulating local temperature, climate, runoff and infiltration, and place for meeting, conducting religious and spiritual activities, holding social events such as marriage and mourning, playing station for children and court for football and other traditional games. As a result of its aesthetic quality and scenic beauty, it is considered as recreational place for improving mental and physical health. The study draws relevant land use planning and management solution in the improvement of socio-ecological resilience in the Jefoure land use system. The study suggests the landscape needs to be registrar as heritage site for recognizing the wisdom of the community and enhancing the conservation mechanisms.

Keywords: cultural landscape, ecosystem services, Gurage, Jefoure

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Authors: Pradyumna R., Sridhar S., A. Satyanarayana, Alok S. Chauhan, Baig M. A. H.

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Modern turbine engines for aerospace applications need precision investment cast components such as integrally cast rotors and stators, for their hot end turbine stages. Traditionally, these turbines are used as starter engines. In recent times, such engines are also used for strategic missile applications. The rotor/stator castings consist of a central hub (shrouded in some designs) over which a number of aerofoil shaped blades are located. Since these components cannot be machined, investment casting is the only available route for manufacture and hence stringent dimensional aerospace quality has to be in-built in the casting process itself. In the process of investment casting, pattern generation by injection of wax into dedicated dies/moulds is the first critical step. Traditional approach deals in producing individual blades with hub/shroud features through wax injection and assembly of a set of such injected patterns onto a dedicated and precisely manufactured fixture to wax-weld and generate an integral wax pattern, a process known as the ‘segmental approach’. It is possible to design a single-injection die with retractable metallic inserts in the case of untwisted blades of stator patterns without the shroud. Such an approach is also possible for twisted blades of rotors with highly complex design of inter-blade inserts and retraction mechanisms. DMRL has for long established methods and procedures for the above to successfully supply precision castings for various defence related projects. In recent times, urea based soluble insert approach has also been successfully applied to overcome the need to design and manufacture a precision assembly fixture, leading to substantial reduction in component development times. Present paper deals in length various approaches tried and established at DMRL to generate precision wax patterns for aerospace quality turbine rotors and stators. In addition to this, the importance of simulation in solving issues related to wax injection is also touched upon.

Keywords: die/mold and fixtures, integral rotor/stator, investment casting, wax patterns, simulation

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Authors: Y. B. Sharma, K. B. Biswas

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This research project examines a 5000 cal yr BP sediment core record to reveal the consequences of human impact and climate variability on the tropical dry forests of the Mahi river basin, western India. To date there has been little research to assess the impact of climate variability and human impact on the vegetation dynamics of this region. There has also been little work to link changes in vegetation cover to documented changes in the basin hydrology over the past 100 years – although it is assumed that the two are closely linked. The key objective of this research project therefore is to understand the driving mechanisms responsible for the abrupt changes in the Mahi river basin as detailed in historical documentation and its impact on water resource management. The Mahi river basin is located in western India (22° 11’-24° 35’ N 72° 46’-74° 52’ E). Mahi river arises in the Malwa Plateau, Madhya Pradesh near Moripara and flows through the uplands and alluvial plain of Rajasthan and Gujarat provinces before draining into the Gulf of Cambay. Palaeoecological procedures (sedimentology, geochemical analysis, C&N isotopes and fossil pollen evidences) have been applied on sedimentary sequences collected from lakes in the Mahi basin. These techniques then facilitate to reconstruct the soil erosion, nutrient cycling, vegetation changes and climatic variability over the last 5000 years. Historical documentation detailing changes in demography, climate and landscape use over the past 100 years in this region will also be collated to compare with the most recent palaeoecological records. The results of the research work provide a detailed record of vegetation change, soil erosion, changes in aridity, and rainfall patterns in the region over the past 5000 years. This research therefore aims to determine the drivers of change and natural variability in the basin. Such information is essential for its current and future management including restoration.

Keywords: human impact, climate variability, vegetation cover, hydrology, water resource management, Mahi river basin, sedimentology, geochemistry, fossil pollen, nutrient cycling, vegetation changes, palaeoecology, aridity, rainfall, drivers of change

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Authors: Periklis Brakatsoulas

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Recent empirical research shows a growing interest in investment decision-making under market anomalies that contradict the rational paradigm. Momentum is undoubtedly one of the most robust anomalies in the empirical asset pricing research and remains surprisingly lucrative ever since first documented. Although predominantly phenomena identified across equities, momentum premia are now evident across various asset classes. Yet few many attempts are made so far to provide traders a diversified portfolio of strategies across different assets and markets. Moreover, literature focuses on patterns from past returns rather than mechanisms to signal future price directions prior to momentum runs. The aim of this paper is to develop a diversified portfolio approach to price distortion signals using daily position data on stocks, credit derivatives, and bonds. An algorithm allocates assets periodically, and new investment tactics take over upon price momentum signals and across different ranking groups. We focus on momentum life cycles, trend reversals, and price acceleration signals. The main effort here concentrates on the density, time span and maturity of momentum phenomena to identify consistent patterns over time and measure the predictive power of buy-sell signals generated by these anomalies. To tackle this, we propose a two-stage modelling process. First, we generate forecasts on core macroeconomic drivers. Secondly, satellite models generate market risk forecasts using the core driver projections generated at the first stage as input. Moreover, using a combination of the ARFIMA and FIGARCH models, we examine the dependence of consecutive observations across time and portfolio assets since long memory behavior in volatilities of one market appears to trigger persistent volatility patterns across other markets. We believe that this is the first work that employs evidence of volatility transmissions among derivatives, equities, and bonds to identify momentum life cycle patterns.

Keywords: forecasting, long memory, momentum, returns

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Authors: Carmen Sica, Elena M. Scalisi, Sara Ignoto, Ludovica Palmeri, Martina Contino, Greta Ferruggia, Antonio Salvaggio, Santi C. Pavone, Gino Sorbello, Loreto Di Donato, Roberta Pecoraro, Maria V. Brundo

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Recently, a rise in the use of wireless internet technologies such as Wi-Fi and 5G routers/modems have been demonstrated. These devices emit a considerable amount of electromagnetic radiation (EMR), which could interact with the male reproductive system either by thermal or non-thermal mechanisms. The aim of this study was to investigate the direct in vitro influence of 5G radiation on sperm quality in Mytilus galloprovincialis, considered an excellent model for reproduction studies. The experiments at 27 GHz were conducted by using a no commercial high gain pyramidal horn antenna. To evaluate the specific absorption rate (SAR), a numerical simulation has been performed. The resulting incident power density was significantly lower than the power density limit of 10 mW/cm2 set by the international guidelines as a limit for nonthermal effects above 6 GHz. However, regarding temperature measurements of the aqueous sample, it has been verified an increase of 0.2°C, compared to the control samples. This very low-temperature increase couldn’t interfere with experiments. For experiments, sperm samples taken from sexually mature males of Mytilus galloprovincialis were placed in artificial seawater, salinity 30 + 1% and pH 8.3 filtered with a 0.2 m filter. After evaluating the number and quality of spermatozoa, sperm cells were exposed to electromagnetic fields a 27GHz. The effect of exposure on sperm motility and quality was evaluated after 10, 20, 30 and 40 minutes with a light microscope and also using the Eosin test to verify the vitality of the gametes. All the samples were performed in triplicate and statistical analysis was carried out using one-way analysis of variance (ANOVA) with Turkey test for multiple comparations of means to determine differences of sperm motility. A significant decrease (30%) in sperm motility was observed after 10 minutes of exposure and after 30 minutes, all sperms were immobile and not vital. Due to little literature data about this topic, these results could be useful for further studies concerning a great diffusion of these new technologies.

Keywords: mussel, spermatozoa, sperm motility, millimeter waves

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Authors: Grzegorz Swiderski, Agata Jablonska-Trypuc, Natalia Popow, Renata Swislocka, Wlodzimierz Lewandowski

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Doxorubicin belongs to the group of anthracycline antitumor antibiotics. Because of the wide spectrum of actions, it is one of the most widely used anthracycline antibiotics, including the treatment of breast, ovary, bladder, lung cancers as well as neuroblastoma, lymphoma, leukemia and myeloid leukemia. Antitumor activity of doxorubicin is based on the same mechanisms as for most anthracyclines. Like the metal ions affect the nucleic acids on many biological processes, so the environment of the metal chelates of antibiotics can have a significant effect on the pharmacological properties of drugs. Complexation of anthracyclines with metal ions may contribute to the production of less toxic compounds. In the framework of this study, the composition of complexes obtained in aqueous solutions of doxorubicin with metal ions (Cu2+ and Zn2+). Complexation was analyzed by spectrophotometric titration in aqueous solution at pH 7.0. The pH was adjusted with 0.02M Tris-HCl buffer. The composition of the complexes found was Cu: doxorubicin (1: 2) and a Zn: doxorubicin (1: 1). The effect of Dox, Dox-Cu and Dox-Zn was examined in MCF-7 breast cancer cell line, which were obtained from American Type Culture Collection (ATCC). The compounds were added to the cultured cells for a final concentration in the range of 0,01µM to 0,5µM. The number of MCF-7 cells with division into living and dead, was determined by direct counts of cells with the use of trypan blue dye using LUNA Logos Biosystems cell counter. ApoTox-Glo Triplex Assay (Promega, Madison, Wisconsin, USA) was used according to the manufacturer’s instructions to measure the MCF-7 cells’ viability, cytotoxicity and apoptosis. We observed a decrease in cells proliferation in a dose-dependent manner. An increase in cytotoxicity and decrease in viability in the ApoTox Triplex assay was also showed for all tested compounds. Apoptosis, showed as caspase 3/7 activation, was observed only in Dox treatment. In Dox-Zn and Dox-Cu caspase 3/7 activation was not observed. This work was financially supported by National Science Centre, Poland, under the research project number 2014/13/B/NZ7/02 352.

Keywords: anticancer properties, anthracycline antibiotic, doxorubicine, metal complexes

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Authors: Bar Shapira-Youngster, Sima Amram-Vaknin, Yuliya Lipshits-Braziler

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The study examined how 811 Israelis experienced and coped with the COVID-19 lockdown. Stress, uncertainty, and loss of control were reported as common emotional experiences. Two main difficulties were reported: Loneliness and health and emotional concerns. Frequent explanations for the virus's emergence were: scientific or faith reasoning. The most prevalent coping strategies were distraction activities and acceptance. Reducing the use of maladaptive coping strategies has important implications for mental health outcomes. Objectives: COVID-19 has been recognized as a collective, continuous traumatic stressor. The present study examined how individuals experienced, perceived, and coped with this traumatic event during the lockdown in Israel in April 2020. Method: 811 Israelis (71.3% were women; mean age 43.7, SD=13.3)completed an online semi-structured questionnaire consisting two sections: In the first section, participants were asked to report background information. In the second section, they were asked to answer 8 open-ended questions about their experience, perception, and coping with the covid-19 lockdown. Participation was voluntary, and anonymity was assured, they were not offered compensation of any kind. The data were subjected to qualitative content analysis that seeks to classify the participants` answers into an effective number of categories that represent similar meanings. Our content analysis of participants’ answers extended far beyond simple word counts; our objective was to try to identify recurrent categories that characterized participants’ responses to each question. We sought to ensure that the categories regarding the different questions are as mutually exclusive and exhaustive as possible. To ensure robust analysis, the data were initially analyzed by the first author, and a second opinion was then sought from research colleagues. Contribution: The present research expands our knowledge of individuals' experiences, perceptions, and coping mechanisms with continuous traumatic events. Reducing the use of maladaptive coping strategies has important implications for mental health outcomes.

Keywords: Covid-19, emotional distress, coping, continuous traumatic event

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Authors: Polina Prokopovich

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Despite the well-established dependence of cartilage mechanical properties on the frequency of the applied load, most research in the field is carried out in either load-free or constant load conditions because of the complexity of the equipment required for the determination of time-dependent properties. These simpler analyses provide a limited representation of cartilage properties thus greatly reducing the impact of the information gathered hindering the understanding of the mechanisms involved in this tissue replacement, development and pathology. More complex techniques could represent better investigative methods, but their uptake in cartilage research is limited by the highly specialised training required and cost of the equipment. There is, therefore, a clear need for alternative experimental approaches to cartilage testing to be deployed in research and clinical settings using more user-friendly and financial accessible devices. Frequency dependent material properties can be determined through rheometry that is an easy to use requiring a relatively inexpensive device; we present how a commercial rheometer can be adapted to determine the viscoelastic properties of articular cartilage. Frequency-sweep tests were run at various applied normal loads on immature, mature and trypsinased (as model of osteoarthritis) cartilage samples to determine the dynamic shear moduli (G*, G′ G″) of the tissues. Moduli increased with increasing frequency and applied load; mature cartilage had generally the highest moduli and GAG depleted samples the lowest. Hydraulic permeability (KH) was estimated from the rheological data and decreased with applied load; GAG depleted cartilage exhibited higher hydraulic permeability than either immature or mature tissues. The rheometer-based methodology developed was validated by the close comparison of the rheometer-obtained cartilage characteristics (G*, G′, G″, KH) with results obtained with more complex testing techniques available in literature. Rheometry is relatively simpler and does not require highly capital intensive machinery and staff training is more accessible; thus the use of a rheometer would represent a cost-effective approach for the determination of frequency-dependent properties of cartilage for more comprehensive and impactful results for both healthcare professional and R&D.

Keywords: tissue, rheometer, biomaterial, cartilage

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Authors: Mehri Sadat Alavinasab Ashgezari, Gholam Reza Nabi Bidhendi, Fatemeh Sadat Alavinasab Ashkezari

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Atmospheric aerosol loading (AAL) from anthropogenic sources is an evidence in industrial development. The accelerated trends in material consumption at the global scale in recent years demonstrate consumption paradigms sensible to the planetary boundaries (PB). This paper is a statistical approach on recognizing the path of climate-relevant bulk materials production (CBMP) of steel, cement and plastics to AAL via an updated and validated spatiotemporal distribution. The methodology of statistical analysis used the most updated regional or global databases or instrumental technologies. This corresponded to a selection of processes and areas capable for tracking AAL within the last decade, analyzing the most validated data while leading to explore the behavior functions or models. The results also represented a correlation within socio economic metabolism idea between the materials specified as macronutrients of society and AAL as a PB with an unknown threshold. The selected country contributors of China, India, US and the sample country of Iran show comparable cumulative AAL values vs to the bulk materials domestic extraction and production rate in the study period of 2012 to 2022. Generally, there is a tendency towards gradual descend in the worldwide and regional aerosol concentration after 2015. As of our evaluation, a considerable share of human role, equivalent 20% from CBMP, is for the main anthropogenic species of aerosols, including sulfate, black carbon and organic particulate matters too. This study, in an innovative approach, also explores the potential role of AAL control mechanisms from the economy sectors where ordered and smoothing loading trends are accredited through the disordered phenomena of CBMP and aerosol precursor emissions. The equilibrium states envisioned is an approval to the well-established theory of Spin Glasses applicable in physical system like the Earth and here to AAL.

Keywords: atmospheric aeroso loading, material flows, climate bulk materials, industrial ecology

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Authors: Valeria Arcucci, Musarat Ishaq, Steven A. Stacker, Greg J. Goodall, Marc G. Achen

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Metastasis is the lethal aspect of cancer for most patients. Remodelling of lymphatic vessels associated with a tumour is a key initial step in metastasis because it facilitates the entry of cancer cells into the lymphatic vasculature and their spread to lymph nodes and distant organs. Although it is clear that vascular endothelial growth factors (VEGFs), such as VEGF-C and VEGF-D, are key drivers of lymphatic remodelling, the means by which many signaling pathways in endothelial cells are coordinately regulated to drive growth and remodelling of lymphatics in cancer is not understood. We seek to understand the broader molecular mechanisms that control cancer metastasis, and are focusing on microRNAs, which coordinately regulate signaling pathways involved in complex biological responses in health and disease. Here, using small RNA sequencing, we found that a specific microRNA, miR-132, is upregulated in expression in lymphatic endothelial cells (LECs) in response to the lymphangiogenic growth factors. Interestingly, ectopic expression of miR-132 in LECs in vitro stimulated proliferation and tube formation of these cells. Moreover, miR-132 is expressed in lymphatic vessels of a subset of human breast tumours which were previously found to express high levels of VEGF-D by immunohistochemical analysis on tumour tissue microarrays. In order to dissect the complexity of regulation by miR-132 in lymphatic biology, we performed Argonaute HITS-CLIP, which led us to identify the miR-132-mRNA interactome in LECs. We found that this microRNA in LECs is involved in the control of many different pathways mainly involved in cell proliferation and regulation of the extracellular matrix and cell-cell junctions. We are now exploring the functional significance of miR-132 targets in the biology of LECs using biochemical techniques, functional in vitro cell assays and in vivo lymphangiogenesis assays. This project will ultimately define the molecular regulation of lymphatic remodelling by miR-132, and thereby identify potential therapeutic targets for drugs designed to restrict the growth and remodelling of tumour lymphatics resulting in metastatic spread.

Keywords: argonaute HITS-CLIP, cancer, lymphatic remodelling, miR-132, VEGF

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Authors: Fitria D. Ayuningtyas, Anggraini Barlian

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Green turtle (Chelonia mydas) is one of TSD (Temperature-dependent Sex Determination, TSD) animals which sex is determined by the egg’s incubation temperature. GSD (Genotypic Sex Determination) homologous genes such as Wilms’ Tumor (Wt1) and Forkhead Box L2 (FoxL2) play a role in TSD animal sex determination process. Wt1 plays a role in both male pathway, as a transcription factor for Sf1 gene and in female pathway, as a transcription factor for Dax1. FoxL2 plays a role specifically in female sex determination, and known as transcriptional factor for Aromatase gene. Until now, research on the pattern of Wt1 and FoxL2 genes expression in C.mydas has not been conducted yet. The aim of this research is to know the pattern of Wt1 and FoxL2 genes expression in Mesonephros-Gonad (MG) complexes of Chelonia mydas embryos incubated in masculinizing temperature (MT) and feminizing temperature (FT). Eggs of C.mydas incubated in 3 different stage of TSP (Thermosensitive Period) at masculinizing temperature (26±10C, MT) and feminizing temperature (31±10C FT). Mesonefros-gonad complexes were isolated at Pre-TSP stage (FT at days 14th, MT at days 24th), TSP stage (FT at days 24th, MT at days 36th) and differentiated stage (FT at days 40th, MT at days 58th). RNA from mesonephros-gonad (MG) complexes were converted into cDNA by RT-PCR process, and the pattern of Wt1 and FoxL2 genes expression is analyzed by quantitative Real Time PCR (qPCR) method, β-actin gene is used as an internal control. The pattern of Wt1 gene expression in Pre-TSP stage was almost the same between MG complexes incubated at MT or FT, while TSP and differentiation stage, the pattern of Wt1 gene expression in MG complexes incubated at MT or FT was increased. Wt1 gene expression of MG complexes that incubated at FT was higher than at MT. There was a difference pattern between Wt1 gene expression in this research compared to the previous research in protein level. It could be assumed that the difference caused by post-transcriptional regulation mechanisms before mRNA of Wt1 gene translated into protein structure. The pattern of FoxL2 gene expression in Pre-TSP stage was almost the same between MG complexes that incubated at MT and FT, and increased in both TSP and differentiated stage. The FoxL2 gene expression in MG complexes that incubated in FT is higher than MT on TSP and differentiated stage. Based on the results of this research, it can be assumed that Wt1 and FoxL2 gene were expressed in MG complexes that incubated both at MT and FT since Pre-TSP stage. The pattern of Wt1 gene expression was increased in every stage of gonadal development, and so do the pattern of FoxL2 gene expression. Wt1 and FoxL2 gene expressions were higher in MG complexes incubated at FT than MT.

Keywords: chelonia mydas, FoxL2, gene expression, TSD, Wt1

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Authors: Vivian A. Panes, Raymond John S. Rebong, Miel Q. Diaz

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Moringa oleifera Lam. is known mainly for its high nutritional value and medicinal properties contributing to its popular reputation as a 'miracle plant' in the tropical climates where it usually grows. The main objective of this study is to discover the genes and gene products involved in abiotic stress-induced activity that may impact the M. oleifera Lam. mature seeds as well as their corresponding functions. In this study, RNA-sequencing and de novo transcriptome assembly were performed using two assemblers, Trinity and Oases, which produced 177,417 and 120,818 contigs respectively. These transcripts were then subjected to various bioinformatics tools such as Blast2GO, UniProt, KEGG, and COG for gene annotation and the analysis of relevant metabolic pathways. Furthermore, FPKM analysis was performed to identify gene expression levels. The sequences were filtered according to the 'response to stress' GO term since this study dealt with stress response. Clustered Orthologous Groups (COG) showed that the highest frequencies of stress response gene functions were those of cytoskeleton which make up approximately 14% and 23% of stress-related sequences under Trinity and Oases respectively, recombination, repair and replication at 11% and 14% respectively, carbohydrate transport and metabolism at 23% and 9% respectively and defense mechanisms 16% and 12% respectively. KEGG pathway analysis determined the most abundant stress-response genes in the phenylpropanoid biosynthesis at counts of 187 and 166 pathways for Oases and Trinity respectively, purine metabolism at 123 and 230 pathways, and biosynthesis of antibiotics at 105 and 102. Unique and cumulative GO term counts revealed that majority of the stress response genes belonged to the category of cellular response to stress at cumulative counts of 1,487 to 2,187 for Oases and Trinity respectively, defense response at 754 and 1,255, and response to heat at 213 and 208, response to water deprivation at 229 and 228, and oxidative stress at 508 and 488. Lastly, FPKM was used to determine the levels of expression of each stress response gene. The most upregulated gene encodes for thiamine thiazole synthase chloroplastic-like enzyme which plays a significant role in DNA damage tolerance. Data analysis implies that M. oleifera stress response genes are directed towards the effects of climate change more than other stresses indicating the potential of M. oleifera for cultivation in harsh environments because it is resistant to climate change, pathogens, and foreign invaders.

Keywords: stress response, genes, Moringa oleifera, transcriptomics

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