Search results for: flexible slider crank mechanism

Authors: Moses Mwangi, Geert Verbeke, Geert Molenberghs

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Cross-over designs are commonly used in randomized clinical trials to estimate efficacy of a new treatment with respect to a reference treatment (placebo or standard). The main advantage of using cross-over design over conventional parallel design is its flexibility, where every subject become its own control, thereby reducing confounding effect. Jones & Kenward, discuss in detail more recent developments in the analysis of cross-over trials. We revisit the simple piecewise linear mixed-effects model, proposed by Mwangi et. al, (in press) for its first application in the analysis of cross-over trials. We compared performance of the proposed piecewise linear mixed-effects model with two commonly cited statistical models namely, (1) Grizzle model; and (2) Jones & Kenward model, used in estimation of the treatment effect, in the analysis of randomized cross-over trial. We estimate two performance measurements (mean square error (MSE) and coverage probability) for the three methods, using data simulated from the proposed piecewise linear mixed-effects model. Piecewise linear mixed-effects model yielded lowest MSE estimates compared to Grizzle and Jones & Kenward models for both small (Nobs=20) and large (Nobs=600) sample sizes. It’s coverage probability were highest compared to Grizzle and Jones & Kenward models for both small and large sample sizes. A piecewise linear mixed-effects model is a better estimator of treatment effect than its two competing estimators (Grizzle and Jones & Kenward models) in the analysis of cross-over trials. The data generating mechanism used in this paper captures two time periods for a simple 2-Treatments x 2-Periods cross-over design. Its application is extendible to more complex cross-over designs with multiple treatments and periods. In addition, it is important to note that, even for single response models, adding more random effects increases the complexity of the model and thus may be difficult or impossible to fit in some cases.

Keywords: Evaluation, Grizzle model, Jones & Kenward model, Performance measures, Simulation

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Authors: Siming Wang, Qing Ni, Yu Wu, Ruihai Xu, Hong Ye

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Porous electric heaters, compared to conventional electric heaters, exhibit excellent heating performance due to their large specific surface area. Porous electric heaters employ porous metallic materials or conductive porous ceramics as the heating element. The former attains a low heating power with a fixed current due to the low electrical resistivity of metal. Although the latter can bypass the inherent challenges of porous metallic materials, the fabrication process of the conductive porous ceramics is complicated and high cost. This work proposed a porous ceramic electric heater with dielectric honeycomb ceramic as a substrate and surface conductive coating as a heating element. The conductive coating was prepared by the sol-gel method using silica sol and methyl trimethoxysilane as raw materials and graphite powder as conductive fillers. The conductive mechanism and degradation reason of the conductive coating was studied by electrical resistivity and thermal stability analysis. The heating performance of the proposed heater was experimentally investigated by heating air and deionized water. The results indicate that the electron transfer is achieved by forming the conductive network through the contact of the graphite flakes. With 30 wt% of graphite, the electrical resistivity of the conductive coating can be as low as 0.88 Ω∙cm. The conductive coating exhibits good electrical stability up to 500°C but degrades beyond 600°C due to the formation of many cracks in the coating caused by the weight loss and thermal expansion. The results also show that the working medium has a great influence on the volume power density of the heater. With air under natural convection as the working medium, the volume power density attains 640.85 kW/m3, which can be increased by 5 times when using deionized water as the working medium. The proposed honeycomb ceramic electric heater has the advantages of the simple fabrication method, low cost, and high volume power density, demonstrating great potential in the fluid heating field.

Keywords: conductive coating, honeycomb ceramic electric heater, high specific surface area, high volume power density

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Authors: Sarocha Vivatvakin, Thanaporn Ratchataswan, Thiratest Leesutipornchai, Komkrit Ruangritchankul, Somboon Keelawat, Virachai Kerekhanjanarong, Patnarin Mahattanasakul, Saknan Bongsebandhu-Phubhakdi

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In this globalization era, much attention has been drawn to various molecular biomarkers, which may have the potential to predict the progression of cancer. Epidermal growth factor receptor (EGFR) is the classic member of the ErbB family of membrane-associated intrinsic tyrosine kinase receptors. EGFR expression was found in several organs throughout the body as its roles involve in the regulation of cell proliferation, survival, and differentiation in normal physiologic conditions. However, anomalous expression, whether over- or under-expression is believed to be the underlying mechanism of pathologic conditions, including carcinogenesis. Even though numerous discussions regarding the EGFR as a prognostic tool in head and neck cancer have been established, the consensus has not yet been met. The aims of the present study are to assess the correlation between the level of EGFR expression and demographic data as well as clinicopathological features and to evaluate the ability of EGFR as a reliable prognostic marker. Furthermore, another aim of this study is to investigate the probable pathophysiology that explains the finding results. This retrospective study included 30 squamous cell laryngeal carcinoma patients treated at King Chulalongkorn Memorial Hospital from January 1, 2000, to December 31, 2004. EGFR expression level was observed to be significantly downregulated with the progression of the laryngeal cancer stage. (one way ANOVA, p = 0.001) A statistically significant lower EGFR expression in the late stage of the disease compared to the early stage was recorded. (unpaired t-test, p = 0.041) EGFR overexpression also showed the tendency to increase recurrence of cancer (unpaired t-test, p = 0.128). A significant downregulation of EGFR expression was documented in advanced stage laryngeal cancer. The results indicated that EGFR level correlates to prognosis in term of stage progression. Thus, EGFR expression might be used as a prevailing biomarker for laryngeal squamous cell carcinoma prognostic prediction.

Keywords: downregulation, epidermal growth factor receptor, immunohistochemistry, laryngeal squamous cell carcinoma

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Authors: Paolo Magnata

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The energy market in the Philippines remains to have one of the highest electricity rates in the region averaging at US$0.16/kWh (PHP6.89/kWh), excluding VAT, as opposed to the overall energy market average of US$0.13/kWh. The movement towards renewable energy, specifically solar energy, will pose as an expensive one with the country’s energy sector providing Feed-in-Tariff rates as high as US$0.17/kWh (PHP8.69/kWh) for solar energy power plants. Increasing the share of renewables at the current state of the energy regulatory background would yield a three-fold increase in residential electricity bills. The issue lies in the uniform charge that consumers bear regardless of where the electricity is sourced resulting in rates that only consider costs and not the consumers. But if they are given the option to choose where their electricity comes from, a number of consumers may potentially choose economically costlier sources of electricity due to higher levels of utility coupled with the willingness to pay of consuming environmentally-friendly sourced electricity. A contingent valuation survey was conducted to determine their willingness-to-pay for solar energy on a sample that was representative of Metro Manila to elicit their willingness-to-pay and a Single Bounded Dichotomous Choice and Double Bounded Dichotomous Choice analysis was used to estimate the amount they were willing to pay. The results showed that Metro Manila residents are willing to pay a premium on top of their current electricity bill amounting to US$5.71 (PHP268.42) – US$9.26 (PHP435.37) per month which is approximately 0.97% - 1.29% of their monthly household income. It was also discovered that besides higher income of households, a higher level of self-perceived knowledge on environmental awareness significantly affected the likelihood of a consumer to pay the premium. Shifting towards renewable energy is an expensive move not only for the government because of high capital investment but also to consumers; however, the Green Energy Option (a policy mechanism which gives consumers the option to decide where their electricity comes from) can potentially balance the shift of the economic burden by transitioning from a uniformly charged electricity rate to equitably charging consumers based on their willingness to pay for renewably sourced energy.

Keywords: contingent valuation, dichotomous choice, Philippines, solar energy

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Authors: Chakrapani Pullagummi, Arun Jyothi Bheemagani, B. Chandra Sekhar Singh, Prem Kumar, A. Roja Rani

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Diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion and its action. The objective of present study was alloxan induced diabetes in S.D (Sprague Dawley) rats, treated with leaf extract of Andrographis paniculata and bark extract of Erythrina indica. Plant extract treated rats were analyzed biochemically and molecularly. on normal and diabetic rats. The changes in MDA (lipid peroxidation) and glucose (by GOD method) levels in blood of both normal and diabetic rat were analyzed. Diabetes induced rats were treated with methanolic extracts of Andrographis paniculata leaf and Erythrina indica bark which are of medicinal importance. Later after inducing diabetes the rats were treated with medicinal plant extracts, Andrographis paniculata leaf and Erythrina indica bark which are well known for their anti diabetic and antioxidative property in order to control the glucose and MDA levels. The blood plasma of diabetic and normal rats was analyzed for the levels of MDA (lipid peroxidation) and glucose levels. Results of this study suggested that the Andrographis paniculata leaf and Erythrina indica can be used as a potential natural antidiabetic agent for treating and postponing the appearance of complications that arise due to Diabetes. Molecular study deals with the analysis of binding mechanism of 2 selected natural compounds from Andrographis and Erythrina extracts against the novel target for type T2D namely PPAR-γ compared with Rosiglitazone (standard compound). The results revealed that most of the selected herbal lead compounds were effective targets against the receptors. These compounds showed favorable interactions with the amino acid residues thereby substantiating their proven efficacy as anti-diabetic compounds.

Keywords: andrographis paniculata, erythrina indica, alloxan, lipid peroxidation, blood glucose level, PPAR-γ

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Authors: Hacer Kobya Bulut, Kıymet Yeşilçiçek Çalık, Birsel Canan Demirbağ, Hacer Erdöl, Songül Aktaş

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Introduction: As an expression of an emotion which always exists in life, crying is regarded as one of the problematic behaviors of patients by nurses. Towards such patients, nurses may exhibit emotional and behavioral reactions such as feeling helpless, anger, indifferent, defense, and opposition. However crying either meets a need, reduces the tension to cope with problems or helps patient to gain strength. Therefore, nurses must accept that crying is a normal mechanism that reduces emotional tension and should approach a crying patient accordingly. Objective: This study was carried out to evaluate the communicational behaviors of the nurses towards ‘crying patient’. Methods: This descriptive study was conducted with the nurses working at a university hospital in a city in the Eastern Black Sea in June-September 2015. The entire universe was tried to be reached without sampling. 90% of the population was reached and the study was completed with 309 nurses who volunteered to participate in the study. Data were collected through a questionnaire which was prepared reviewing the literature by researchers. Data were evaluated in SPSS analysis program using percentages, numbers and chi-square test with the 95% confidence interval and p <0.05significance level. Findings: The findings showed that the average age of nurses was 31.52 ± 7.96, work experience was 10:09 ± 7.69 and only 22.7% had training about ‘approach to crying patient’ during their education. 97.1% of the nurses often faced with crying patients in their professional lives, 62.8% stated that they faced crying women patients. When they see crying patients, 84.8% of the nurses ‘do not want the patient to cry’, 80.9% wonder ‘why they are crying’, % 79.6 ‘feel uneasiness’,% 79.3 ‘feel sorry’ and 41.4% ‘ feel helpless’. The question ‘Why do you think the patient is crying?’ was answered by 93.5% nurses as ‘they are suffering’, by 86.1% ‘they are helpless’, 80.9% ‘they are sad’, 79.6% ‘they need help’, 54.4% ‘because they feel inadequate,’ and 44.7% ‘they fail to control their crying behavior. ‘How do you approach to your patient when she/he is crying?’ question was answered by 82.5% of nurses as ‘I would console’, 77.3% as ‘I would ask the reason’, 63.1% as ‘I would try to stop her from crying’ all of which are actually inappropriate nursing approaches. However, 92.2% of the nurses stated that ‘I do not judge the crying patient’, ‘87.1% said ‘I allocate time to crying patients’ and 85.8% said ‘ I ask patient whether they want to cry alone’. The study showed that educational background and work experience of the nurses affected the appropriate approach to crying patients (P <0.05). Conclusion: As a result of the study, it was found out that nurses do not want patients to cry, so they exhibit inappropriate approach such as consoling the patients and they have difficulty in approaching crying patients.

Keywords: approach to patient, communication, crying patient, nurse, Turkey

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Authors: Monika Jurkeviciute, Amia Enam, Johanna Torres Bonilla, Henrik Eriksson

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Introduction: Many evaluations of eHealth interventions conclude that the evidence for improved clinical outcomes is limited, especially when the intervention is short, such as one year. Often, evaluation design does not address the feasibility of achieving clinical outcomes. Evaluations are designed to reflect upon clinical goals of intervention without utilizing the opportunity to illuminate effects on organizations and cost. A comprehensive design of evaluation can better support decision-making regarding the effectiveness and potential transferability of eHealth. Hence, the purpose of this paper is to present a feasible and comprehensive design of evaluation for eHealth intervention, including the design process in different contexts. Methodology: The situation of limited feasibility of clinical outcomes was foreseen in the European Union funded project called “DECI” (“Digital Environment for Cognitive Inclusion”) that is run under the “Horizon 2020” program with an aim to define and test a digital environment platform within corresponding care models that help elderly people live independently. A complex intervention of eHealth implementation into elaborate care models in four different countries was planned for one year. To design the evaluation, a participative approach was undertaken using Pettigrew’s lens of change and transformations, including context, process, and content. Through a series of workshops, observations, interviews, and document analysis, as well as a review of scientific literature, a comprehensive design of evaluation was created. Findings: The findings indicate that in order to get evidence on clinical outcomes, eHealth interventions should last longer than one year. The content of the comprehensive evaluation design includes a collection of qualitative and quantitative methods for data gathering which illuminates non-medical aspects. Furthermore, it contains communication arrangements to discuss the results and continuously improve the evaluation design, as well as procedures for monitoring and improving the data collection during the intervention. The process of the comprehensive evaluation design consists of four stages: (1) analysis of a current state in different contexts, including measurement systems, expectations and profiles of stakeholders, organizational ambitions to change due to eHealth integration, and the organizational capacity to collect data for evaluation; (2) workshop with project partners to discuss the as-is situation in relation to the project goals; (3) development of general and customized sets of relevant performance measures, questionnaires and interview questions; (4) setting up procedures and monitoring systems for the interventions. Lastly, strategies are presented on how challenges can be handled during the design process of evaluation in four different countries. The evaluation design needs to consider contextual factors such as project limitations, and differences between pilot sites in terms of eHealth solutions, patient groups, care models, national and organizational cultures and settings. This implies a need for the flexible approach to evaluation design to enable judgment over the effectiveness and potential for adoption and transferability of eHealth. In summary, this paper provides learning opportunities for future evaluation designs of eHealth interventions in different national and organizational settings.

Keywords: ehealth, elderly, evaluation, intervention, multi-cultural

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Authors: Morgane Chatard, Clémentine Puech, Nathalie Perek, Frédéric Roche

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Several neurological disorders are linked to repeated hypoxia. The impact of such repeated hypoxic stress, on endothelial cells function of the blood-brain barrier (BBB) is little studied in the literature. Indeed, the study of hypoxic stress in cellular pathways is complex using hypoxia exposure because HIF 1α (factor induced by hypoxia) has a short half life. Our study presents an innovative induction method of repeated hypoxic stress, more reproducible, which allows us to study its impacts on an in vitro contact co-culture BBB model. Repeated hypoxic stress was induced by hydralazine (a mimetic agent of hypoxia pathway) during two hours and repeated during 24 hours. Then, BBB integrity was assessed by permeability measurements (transendothelial electrical resistance and membrane permeability), tight junction protein expressions (cell-ELISA and confocal microscopy) and by studying expression and activity of efflux transporters. First, this study showed that repeated hypoxic stress leads to a BBB’s dysfunction illustrated by a significant increase in permeability. This loss of membrane integrity was linked to a significant decrease of tight junctions’ protein expressions, facilitating a possible transfer of potential cytotoxic compounds in the brain. Secondly, we demonstrated that brain microvascular endothelial cells had set-up defence mechanism. These endothelial cells significantly increased the activity of their efflux transporters which was associated with a significant increase in their expression. In conclusion, repeated hypoxic stress lead to a loss of BBB integrity with a decrease of tight junction proteins. In contrast, endothelial cells increased the expression of their efflux transporters to fight against cytotoxic compounds brain crossing. Unfortunately, enhanced efflux activity could also lead to reducing pharmacological drugs delivering to the brain in such hypoxic conditions.

Keywords: BBB model, efflux transporters, repeated hypoxic stress, tigh junction proteins

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Authors: Asselah Amel, Affif Chaouche M'yassa, Toudji Amira, Tazerouti Amel

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This study covers two aspects ; the biodegradability and the performances in corrosion inhibition of a series of synthetized surfactants namely Φ- sodium methyl ester sulfonates (Φ-MES: C₁₂-MES, C₁₄-MES and C₁₆-MES. The biodegradability of these organic compounds was studied using the respirometric method, ‘the standard ISO 9408’. Degradation was followed by analysis of dissolved oxygen using the dissolved oxygen meter over 28 days and the results were compared with that of sodium dodecyl sulphate (SDS). The inoculum used consists of activated sludge taken from the aeration basin of the biological wastewater treatment plant in the city of Boumerdes-Algeria. In addition, the anticorrosive performances of Φ-MES surfactants on a carbon steel "X70" were evaluated in an injection water from a well of Hassi R'mel region- Algeria, known as Baremian water, and are compared to sodium dodecyl sulphate. Two technics, the weight loss and the linear polarization resistance corrosion rate (LPR) are used allowing to investigate the relationships between the concentrations of these synthetized surfactants and their surface properties, surface coverage and inhibition efficiency. Various adsorption isotherm models were used to characterize the nature of adsorption and explain their mechanism. The results show that the MES anionic surfactants was readily biodegradable, degrading faster than SDS, about 88% for C₁₂-MES compared to 66% for the SDS. The length of their carbon chain affects their biodegradability; the longer the chain, the lower the biodegradability. The inhibition efficiency of these surfactants is around 78.4% for C₁₂-MES, 76.60% for C₁₄-MES and 98.19% for C₁₆-MES and increases with their concentration and reaches a maximum value around their critical micelle concentrations ( CMCs). Scanning electron microscopy coupled to energy dispersive X-ray spectroscopy allowed to the visualization of a good adhesion of the protective film formed by the surfactants to the surface of the steel. The studied surfactants show the Langmuirian behavior from which the thermodynamic parameters as adsorption constant (Kads), standard free energy of adsorption (〖∆G〗_ads^0 ) are determined. Interaction of the surfactants with steel surface have involved physisorptions.

Keywords: corrosion, surfactants, adsorption, adsorption isotherems

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Authors: Latif Karimi, Yasuhide Mochida

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The purpose of this paper is to study Modern Methods of Construction (MMC); specifically, the prefabrication technology and check the applicability, suitability, and benefits of this construction technique over conventional methods for building new houses in Afghanistan. Construction industry and house building sector are a key contributor to Afghanistan’s economy. However, this sector is challenged with lack of innovation and severe impacts that it has on the environment due to huge amount of construction waste from building, demolition and or renovation activities. This paper studies the prefabrication technology, a popular MMC that is becoming more common, improving in quality and being available in a variety of budgets. Several feasibility studies worldwide have revealed that this method is the way forward in improving construction industry performance as it has been proven to reduce construction time, construction wastes and improve the environmental performance of the construction processes. In addition, this study emphasizes on 'sustainability' in-house building, since it is a common challenge in housing construction projects on a global scale. This challenge becomes more severe in the case of under-developed countries, like Afghanistan. Because, most of the houses are being built in the absence of a serious quality control mechanism and dismissive to basic requirements of sustainable houses; well-being, cost-effectiveness, minimization - prevention of wastes production during construction and use, and severe environmental impacts in view of a life cycle assessment. Methodology: A literature review and study of the conventional practices of building houses in urban areas of Afghanistan. A survey is also being completed to study the potentials and challenges of using prefabrication technology for building modern houses in the cities across the country. A residential housing project is selected for case study to determine the drawbacks of current construction methods vs. prefabrication technique for building a new house. Originality: There are little previous research available about MMC considering its specific impacts on sustainability related to house building practices. This study will be specifically of interest to a broad range of people, including planners, construction managers, builders, and house owners.

Keywords: modern methods of construction (MMC), prefabrication, prefab houses, sustainable construction, modern houses

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Authors: Haifeng Shi, Kun Song, Yili Zhao

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In China, with the extensive promotion of the ‘aging in place’ pension policy as the background, most of the elders will choose to remain in their current homes and communities, finding out of preference or necessity that they will need to remodel their homes to fit their changing needs. This generation elder born in the 1960s to 1970s almost live in the same form of housing-condominium built from 1982 to 2012. Based on the survey of existing multi-family housing, especially in Tianjin, it is found that the current ‘double two-thirds principles’ is becoming the threshold for modification to existing house, particularly in the project of elevators addition to existing condominium (built from 1982 to 2016 without elevators below 6 floors according to the previous building code). Firstly, this article concludes the local policies of elevator addition nationwide, most of which has determined the importance and necessity of the community-based self-organization principle in the operation of the elevator addition. Secondly, by comparing the three existing community management systems (owners' congress, property management system and community committee) in instances, find that the community-based ‘two-thirds’ principle is not conducive to implement for multi-owned property renovation in the community or common accessibility modification in the building. However, analysis the property and other community management related laws, pointing out the shortcomings of the existing community-based ‘two-thirds’ decision-making norms. The analyzation showed that the unit-based and ‘100% principle’ method is more capable of common accessibility in the condominium in China. Differing from existing laws, the unit-based principle will be effective for the process of decision-making and ‘100% principle’ will protect closely profit-related householders for condominium modification in the multi-owned area. These three aspects of the analysis suggest that the establishment of the unit-based self-organization mechanism is a preferred and inevitable method to solve the problem of elevators addition to the existing condominium in China.

Keywords: aging in place, condominium, modification, multi own

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Authors: Chunyang Miao, Bingxin Li, Shanglong Ning, Christopher J. B. Ford

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While it is challenging to fabricate electronic devices close to atomic dimensions in conventional top-down lithography, molecular electronics is promising to help maintain the exponential increase in component densities via using molecular building blocks to fabricate electronic components from the bottom up. It offers smaller, faster, and more energy-efficient electronic and photonic systems. A self-assembled monolayer (SAM) of molecules is a layer of molecules that self-assembles on a substrate. They are mechanically flexible, optically transparent, low-cost, and easy to fabricate. A large-area multi-layer structure has been designed and investigated by the team, where a SAM of designed molecules is sandwiched between graphene and gold electrodes. Each molecule can act as a quantum dot, with all molecules conducting in parallel. When a source-drain bias is applied, significant current flows only if a molecular orbital (HOMO or LUMO) lies within the source-drain energy window. If electrons tunnel sequentially on and off the molecule, the charge on the molecule is well-defined and the finite charging energy causes Coulomb blockade of transport until the molecular orbital comes within the energy window. This produces ‘Coulomb diamonds’ in the conductance vs source-drain and gate voltages. For different tunnel barriers at either end of the molecule, it is harder for electrons to tunnel out of the dot than in (or vice versa), resulting in the accumulation of two or more charges and a ‘Coulomb staircase’ in the current vs voltage. This nanostructure exhibits highly reproducible Coulomb-staircase patterns, together with additional oscillations, which are believed to be attributed to molecular vibrations. Molecules are more isolated than semiconductor dots, and so have a discrete phonon spectrum. When tunnelling into or out of a molecule, one or more vibronic states can be excited in the molecule, providing additional transport channels and resulting in additional peaks in the conductance. For useful molecular electronic devices, achieving the optimum orbital alignment of molecules to the Fermi energy in the leads is essential. To explore it, a drop of ionic liquid is employed on top of the graphene to establish an electric field at the graphene, which screens poorly, gating the molecules underneath. Results for various molecules with different alignments of Fermi energy to HOMO have shown highly reproducible Coulomb-diamond patterns, which agree reasonably with DFT calculations. In summary, this large-area SAM molecular junction is a promising candidate for future electronic circuits. (1) The small size (1-10nm) of the molecules and good flexibility of the SAM lead to the scalable assembly of ultra-high densities of functional molecules, with advantages in cost, efficiency, and power dissipation. (2) The contacting technique using graphene enables mass fabrication. (3) Its well-observed Coulomb blockade behaviour, narrow molecular resonances, and well-resolved vibronic states offer good tuneability for various functionalities, such as switches, thermoelectric generators, and memristors, etc.

Keywords: molecular electronics, Coulomb blokade, electron-phonon coupling, self-assembled monolayer

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Authors: Zhao Xinlei

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In general, interstate relations are diverse and include economic, political, military, and diplomatic. Therefore, by analyzing the development of the relationship between Malaysia and China, we can better verify how the Hirschman effect works between small countries and great powers. This paper mainly adopts qualitative research methods and uses Malaysia's 2020-2022 political crisis as a specific case to verify the practice of the Hirschman effect between small and large countries. In particular, the interest groups in small countries that are closely related to trade with extraordinary abilities, as the primary beneficiaries in the development of trade between the two countries, although they may use their resources to a certain extent to influence the decisions of small countries towards great powers, they do not fundamentally determine the small countries' response to large countries. In this process, the relative power asymmetry between states plays a dominant role, as small states lack trust and suspicion in political diplomacy towards large states based on the perception of threat arising from the relative power asymmetry. When developing bilateral relations with large countries, small states seek practical cooperation to promote economic and trade development but become more cautious in their political ties to avoid being caught in power struggles between large states or being controlled by them. The case of Malaysia-China relations also illustrates that despite the ongoing political crisis in Malaysia, which saw the country go through the transition from (Perikatan Nasional) PN to (Barisan Nasional) BN, different governments have maintained a pragmatic and proactive economic policy towards China to reduce suspicion and mistrust between the two countries in political and diplomatic affairs, thereby enhancing cooperation and interactions between the two countries. At the same time, the Malaysian government is developing multi-dimensional foreign relations and actively participating in multilateral, regional organizations and platforms, such as those organized by the United States, to maintain a relative balance in the influence of the US and China on Malaysia.

Keywords: Hirschman effect, interest groups, Malaysia, China, bilateral relations

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Authors: James Pinfold

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The MoEDAL (Monopole and Exotics Detector at the LHC) experiment deployed at IP8 on the Large Hadron Collider ring was the first dedicated search experiment to take data at the Large Hadron Collider (LHC) in 2010. It was designed to search for Highly Ionizing Particle (HIP) avatars of new physics such as magnetic monopoles, dyons, Q-balls, multiply charged particles, massive, slowly moving charged particles and long-lived massive charge SUSY particles. We shall report on our search at LHC’s Run-2 for Magnetic monopoles and dyons produced in p-p and photon-fusion. In more detail, we will report our most recent result in this arena: the search for magnetic monopoles via the Schwinger Mechanism in Pb-Pb collisions. The MoEDAL detector, originally the first dedicated search detector at the LHC, is being reinstalled for LHC’s Run-3 to continue the search for electrically and magnetically charged HIPs with enhanced instantaneous luminosity, detector efficiency and a factor of ten lower thresholds for HIPs. As part of this effort, we will search for massive l long-lived, singly and multiply charged particles from various scenarios for which MoEDAL has a competitive sensitivity. An upgrade to MoEDAL, the MoEDAL Apparatus for Penetrating Particles (MAPP), is now the LHC’s newest detector. The MAPP detector, positioned in UA83, expands the physics reach of MoEDAL to include sensitivity to feebly-charged particles with charge, or effective charge, as low as 10-3 e (where e is the electron charge). Also, In conjunction with MoEDAL’s trapping detector, the MAPP detector gives us a unique sensitivity to extremely long-lived charged particles. MAPP also has some sensitivity to long-lived neutral particles. The addition of an Outrigger detector for MAPP-1 to increase its acceptance for more massive milli-charged particles is currently in the Technical Proposal stage. Additionally, we will briefly report on the plans for the MAPP-2 upgrade to the MoEDAL-MAPP experiment for the High Luminosity LHC (HL-LHC). This experiment phase is designed to maximize MoEDAL-MAPP’s sensitivity to very long-lived neutral messengers of physics beyond the Standard Model. We envisage this detector being deployed in the UGC1 gallery near IP8.

Keywords: LHC, beyond the standard model, dedicated search experiment, highly ionizing particles, long-lived particles, milli-charged particles

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Authors: Mostafa Najim, Alaa Rahhal, Fadi Khir, Safae Abu Yousef, Amer Aljundi, Feryal Ibrahim, Aliaa Amer, Ahmed Soliman Mohamed, Samira Saleh, Dekra Alfaridi, Ahmed Mahfouz, Sumaya Al-Yafei, Faraj Howady, Mohamad Yahya Khatib, Samar Alemadi

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Background: Coronavirus disease 2019 (COVID-19) increases the risk of coagulopathy among critically ill patients. Although the presence of antiphospholipid antibodies (aPLs) has been proposed as a possible mechanism of COVID-19 induced coagulopathy, their clinical significance among critically ill patients with COVID-19 remains uncertain. Methods: This prospective observational study included patients with COVID-19 admitted to intensive care units (ICU) to evaluate the prevalence and clinical significance of aPLs, including anticardiolipin IgG/IgM, anti-β2-glycoprotein IgG/IgM, and lupus anticoagulant. The study outcomes included the prevalence of aPLs, a primary composite outcome of all-cause mortality, and arterial or venous thrombosis among aPLs positive patients versus aPLs negative patients during their ICU stay. Multiple logistic regression was used to assess the influence of aPLs on the primary composite outcome of mortality and thrombosis. Results: A total of 60 critically ill patients were enrolled. Of whom, 57 (95%) were male, with a mean age of 52.8 ± 12.2 years, and the majority were from Asia (68%). Twenty-two patients (37%) were found to have positive aPLs; of whom 21 patients were positive for lupus anticoagulant, whereas one patient was positive for anti-β2-glycoprotein IgG/IgM. The composite outcome of mortality and thrombosis during ICU did not differ among patients with positive aPLs compared to those with negative aPLs (4 (18%) vs. 6 (16%), aOR= 0.98, 95% CI 0.1-6.7; p-value= 0.986). Likewise, the secondary outcomes, including all-cause mortality, venous thrombosis, arterial thrombosis, discharge from ICU, time to mortality, and time to discharge from ICU, did not differ between those with positive aPLs upon ICU admission in comparison to patients with negative aPLs. Conclusion: The presence of aPLs does not seem to affect the outcomes of critically ill patients with COVID-19 in terms of all-cause mortality and thrombosis. Therefore, clinicians may not screen critically ill patients with COVID-19 for aPLs unless deemed clinically appropriate.

Keywords: antiphospholipid antibodies, critically ill patients, coagulopathy, coronavirus

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Authors: Zahra Kazemi Saleh, Bénédicte Poulin-Charronnat, Annie Vinter

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This study examines the effects of aging on visual statistical learning, using eye-tracking techniques to investigate this cognitive phenomenon. Visual statistical learning is a fundamental brain function that enables the automatic and implicit recognition, processing, and internalization of environmental patterns over time. Some previous research has suggested the robustness of this learning mechanism throughout the aging process, underscoring its importance in the context of education and rehabilitation for the elderly. The study included three distinct groups of participants, including 21 young adults (Mage: 19.73), 20 young-old adults (Mage: 67.22), and 17 old-old adults (Mage: 79.34). Participants were exposed to a series of 12 arbitrary black shapes organized into 6 pairs, each with different spatial configurations and orientations (horizontal, vertical, and oblique). These pairs were not explicitly revealed to the participants, who were instructed to passively observe 144 grids presented sequentially on the screen for a total duration of 7 min. In the subsequent test phase, participants performed a two-alternative forced-choice task in which they had to identify the most familiar pair from 48 trials, each consisting of a base pair and a non-base pair. Behavioral analysis using t-tests revealed notable findings. The mean score for the first group was significantly above chance, indicating the presence of visual statistical learning. Similarly, the second group also performed significantly above chance, confirming the persistence of visual statistical learning in young-old adults. Conversely, the third group, consisting of old-old adults, showed a mean score that was not significantly above chance. This lack of statistical learning in the old-old adult group suggests a decline in this cognitive ability with age. Preliminary eye-tracking results showed a decrease in the number and duration of fixations during the exposure phase for all groups. The main difference was that older participants focused more often on empty cases than younger participants, likely due to a decline in the ability to ignore irrelevant information, resulting in a decrease in statistical learning performance.

Keywords: aging, eye tracking, implicit learning, visual statistical learning

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Authors: Dinuka Herath, Shelley Harrington

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This paper prompts debate about whether disorganization can be positioned as a mechanism that facilitates the creation and enactment of important dynamic capabilities within an organization. This particular article is a conceptual exploration of the link between dynamic capabilities and disorganization and presents the case for agent-based modelling as a viable methodological tool which can be used to explore this link. Dynamic capabilities are those capabilities that an organization needs to sustain competitive advantage in complex environments. Disorganization is the process of breaking down restrictive organizational structures and routines that commonly reside in organizations in order to increase organizational performance. In the 20th century, disorganization was largely viewed as an undesirable phenomenon within an organization. However, the concept of disorganization has been revitalized and garnered research interest in the recent years due to studies which demonstrate some of the advantages of disorganization to an organization. Furthermore, recent Agent-based simulation studies have shown the capability of disorganization to be managed and argue for disorganization to be viewed as an enabler of organizational productivity. Given the natural state of disorganization and resulting fear this can create, this paper argues that instead of trying to ‘correct’ disorganization, it should be actively encouraged to have functional purpose. The study of dynamic capabilities emerged as a result of heightened dynamism and consequentially the very nature of dynamism denotes a level of fluidity and flexibility, something which this paper argues many organizations do not truly foster due to a constrained commitment to organization and order. We argue in this paper that the very state of disorganization is a state that should be encouraged to develop dynamic capabilities needed to not only deal with the complexities of the modern business environment but also to sustain competitive success. The significance of this paper stems from the fact that both dynamic capabilities and disorganization are two concepts that are gaining prominence in their respective academic genres. Despite the attention each concept has received individually, no conceptual link has been established to depict how they actually interact with each other. We argue that the link between these two concepts present a novel way of looking at organizational performance. By doing so, we explore the potential of these two concepts working in tandem in order to increase organizational productivity which has significant implications for both academics and practitioners alike.

Keywords: agent-based modelling, disorganization, dynamic capabilities, performance

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Authors: Randa Alharbi, Vladislav Vyshemirsky

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Systems biology is an important field in science which focuses on studying behaviour of biological systems. Modelling is required to produce detailed description of the elements of a biological system, their function, and their interactions. A well-designed model requires selecting a suitable mechanism which can capture the main features of the system, define the essential components of the system and represent an appropriate law that can define the interactions between its components. Complex biological systems exhibit stochastic behaviour. Thus, using probabilistic models are suitable to describe and analyse biological systems. Continuous-Time Markov Chain (CTMC) is one of the probabilistic models that describe the system as a set of discrete states with continuous time transitions between them. The system is then characterised by a set of probability distributions that describe the transition from one state to another at a given time. The evolution of these probabilities through time can be obtained by chemical master equation which is analytically intractable but it can be simulated. Uncertain parameters of such a model can be inferred using methods of Bayesian inference. Yet, inference in such a complex system is challenging as it requires the evaluation of the likelihood which is intractable in most cases. There are different statistical methods that allow simulating from the model despite intractability of the likelihood. Approximate Bayesian computation is a common approach for tackling inference which relies on simulation of the model to approximate the intractable likelihood. Particle Markov chain Monte Carlo (PMCMC) is another approach which is based on using sequential Monte Carlo to estimate intractable likelihood. However, both methods are computationally expensive. In this paper we discuss the efficiency and possible practical issues for each method, taking into account the computational time for these methods. We demonstrate likelihood-free inference by performing analysing a model of the Repressilator using both methods. Detailed investigation is performed to quantify the difference between these methods in terms of efficiency and computational cost.

Keywords: Approximate Bayesian computation(ABC), Continuous-Time Markov Chains, Sequential Monte Carlo, Particle Markov chain Monte Carlo (PMCMC)

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Authors: Timma Reddy, Srikonda Ramesh

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India has been traditionally vulnerable to natural disasters such as Floods, droughts, cyclones, earthquakes and landslides. It has become a recurrent phenomenon as observed in last five decades. The survey indicates that about 60% of the landmass is prone to earthquakes of various intensities; over 40 million hectares is prone to floods; about 8% of the total area is prone to cyclones and 68% of the area is susceptible to drought. Climate change is likely to be perceived through experience of extreme weather events. There is growing societal concern about climate change, given the potential impacts of associated natural hazards such as cyclones, flooding, earthquakes, landslides etc, hence it is essential and crucial to strengthening our settlements to respond to such calamities. So, the research paper focus is to analyze the effective planning strategy/mechanism to integrate disaster mitigation measures in coastal regions in general and Capital Region of Andhra Pradesh in particular. The basic hypothesis is to govern the appropriate special planning considerations would facilitate to have organized way of protective life and properties from natural disasters. And further to integrate the infrastructure planning with conscious direction would provide an effective mitigations measures. It has been planned and analyzed to Vijayawada city with conscious land use planning with reference to space syntax trajectory in accordance to required social infrastructure such as health facilities, institution areas and recreational and other open spaces. It has been identified that the geographically ideal location with reference to the population densities based on GIS tools the properness strategies can be effectively integrated to protect the life and to save the properties by means of reducing the damage/impact of natural disasters in general earth quake/cyclones or floods in particularly.

Keywords: modular, trajectories, social infrastructure, evidence based syntax, drills and equipments, GIS, geographical micro zoning, high resolution satellite image

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Authors: Thummalapalli CSM Gupta, Banti Sidhiwala

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Mineral oils of naphthenic and paraffinic type have been traditionally been used as insulating liquids in the transformer applications to protect the solid insulation from moisture and ensures effective heat transfer/cooling. The performance of these type of oils have been proven in the field over many decades and the condition monitoring and diagnosis of transformer performance have been successfully monitored through oil properties and dissolved gas analysis methods successfully. Different type of gases representing various types of faults due to components or operating conditions effectively. While large amount of data base has been generated in the industry on dissolved gas analysis for mineral oil based transformer oils and various models for predicting the fault and analysis, oil specifications and standards have also been modified to include stray gassing limits which cover the low temperature faults and becomes an effective preventative maintenance tool that can benefit greatly to know the reasons for the breakdown of electrical insulating materials and related components. Natural esters have seen a rise in popularity in recent years due to their "green" credentials. Some of its benefits include biodegradability, a higher fire point, improvement in load capability of transformer and improved solid insulation life than mineral oils. However, the Stray gases evolution like hydrogen and hydrocarbons like methane (CH4) and ethane (C2H6) show very high values which are much higher than the limits of mineral oil standards. Though the standards for these type esters are yet to be evolved, the higher values of hydrocarbon gases that are available in the market is of concern which might be interpreted as a fault in transformer operation. The current paper focuses on developing a natural ester based transformer oil which shows very levels of stray gassing by standard test methods show much lower values compared to the products available currently and experimental results on various test conditions and the underlying mechanism explained.

Keywords: biodegadability, fire point, dissolved gassing analysis, stray gassing

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Authors: Debashree Ghosh, Preethi Sridhar, Shloka Atul Dhavle

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The judicious and economic consumption of energy for sustainable growth and development is nowadays a thing of primary importance; Phase Change Materials (PCM) provide an ingenious option of storing energy in the form of Latent Heat. Energy storing mechanism incorporating phase change material increases the efficiency of the process by minimizing the difference between supply and demand; PCM heat exchangers are used to storing the heat or non-convectional energy within the PCM as the heat of fusion. The experimental study evaluates the effect of thermo-physical properties, variation in inlet temperature, and flow rate on charging period of a coiled heat exchanger. Secondly, a numerical study is performed on a PCM double pipe heat exchanger packed with two different PCMs, namely, RT50 and Fatty Acid, in the annular region. In this work, the simulation of charging of paraffin wax (RT50) using water as high-temperature fluid (HTF) is performed. Commercial software Ansys-Fluent 15 is used for simulation, and hence charging of PCM is studied. In the Enthalpy-porosity model, a single momentum equation is applicable to describe the motion of both solid and liquid phases. The details of the progress of phase change with time are presented through the contours of melt-fraction, temperature. The velocity contour is shown to describe the motion of the liquid phase. The experimental study revealed that paraffin wax melts with almost the same temperature variation at the two Intermediate positions. Fatty acid, on the other hand, melts faster owing to greater thermal conductivity and low melting temperature. It was also observed that an increase in flow rate leads to a reduction in the charging period. The numerical study also supports some of the observations found in the experimental study like the significant dependence of driving force on the process of melting. The numerical study also clarifies the melting pattern of the PCM, which cannot be observed in the experimental study.

Keywords: latent heat storage, charging period, discharging period, coiled heat exchanger

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Authors: Ozan Kahraman, Hao Feng

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Ultrasonic atomization (UA) is a useful technique for producing a liquid spray for various processes, such as spray drying. Ultrasound generates small droplets (a few microns in diameter) by disintegration of the liquid via cavitation and/or capillary waves, with low range velocity and narrow droplet size distribution. In recent years, UA has been investigated as an alternative for enabling or enhancing ultrasound-mediated unit operations, such as evaporation, separation, and purification. The previous studies on the UA separation of a solvent from a bulk solution were limited to ethanol-water systems. More investigations into ultrasound-mediated separation for other liquid systems are needed to elucidate the separation mechanism. This study was undertaken to investigate the effects of the operational parameters on the ultrasound-mediated separation of three miscible liquid pairs: ethanol-, methanol-, and butanol-water. A 2.4 MHz ultrasonic mister with a diameter of 18 mm and rating power of 24 W was installed on the bottom of a custom-designed cylindrical separation unit. Air was supplied to the unit (3 to 4 L/min.) as a carrier gas to collect the mist. The effects of the initial alcohol concentration, viscosity, and temperature (10, 30 and 50°C) on the atomization rates were evaluated. The alcohol concentration in the collected mist was measured with high performance liquid chromatography and a refractometer. The viscosity of the solutions was determined using a Brookfield digital viscometer. The alcohol concentration of the atomized mist was dependent on the feed concentration, feed rate, viscosity, and temperature. Increasing the temperature of the alcohol-water mixtures from 10 to 50°C increased the vapor pressure of both the alcohols and water, resulting in an increase in the atomization rates but a decrease in the separation efficiency. The alcohol concentration in the mist was higher than that of the alcohol-water equilibrium at all three temperatures. More importantly, for ethanol, the ethanol concentration in the mist went beyond the azeotropic point, which cannot be achieved by conventional distillation. Ultrasound-mediated separation is a promising non-equilibrium method for separating and purifying alcohols, which may result in significant energy reductions and process intensification.

Keywords: azeotropic mixtures, distillation, evaporation, purification, seperation, ultrasonic atomization

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Authors: E. Syngelaki, C. C. F. Schinkel, S. Klatt, E. Hörandl

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Environmental influence can alter the conditions for plant development and can trigger changes in epigenetic variation. Thus, the exposure to abiotic environmental stress can lead to different DNA methylation profiles and may have evolutionary consequences for adaptation. Epigenetic control mechanisms may further influence mode of reproduction. The alpine species R. kuepferi has diploid and tetraploid cytotypes, that are mostly sexual and facultative apomicts, respectively. Hence, it is a suitable model system for studying the correlations of mode of reproduction, ploidy, and environmental stress. Diploid and tetraploid individuals were placed in two climate chambers and treated with low (+7°C day/+2°C night, -1°C cold shocks for three nights per week) and warm (control) temperatures (+15°C day/+10°C night). Subsequently, methylation sensitive-Amplified Fragment-Length Polymorphism (AFPL) markers were used to screen genome-wide methylation alterations triggered by stress treatments. The dataset was analyzed for four groups regarding treatment (cold/warm) and ploidy level (diploid/tetraploid), and also separately for full methylated, hemi-methylated and unmethylated sites. Patterns of epigenetic variation suggested that diploids differed significantly in their profiles from tetraploids independent from treatment, while treatments did not differ significantly within cytotypes. Furthermore, diploids are more differentiated than the tetraploids in overall methylation profiles of both treatments. This observation is in accordance with the increased frequency of apomictic seed formation in diploids and maintenance of facultative apomixis in tetraploids during the experiment. Global analysis of molecular variance showed higher epigenetic variation within groups than among them, while locus-by-locus analysis of molecular variance showed a high number (54.7%) of significantly differentiated un-methylated loci. To summarise, epigenetic variation seems to depend on ploidy level, and in diploids may be correlated to changes in mode of reproduction. However, further studies are needed to elucidate the mechanism and possible functional significance of these correlations.

Keywords: apomixis, cold stress, DNA methylation, Ranunculus kuepferi

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Authors: Fadia Gafri, Kathryn Mckintosh, Louise Young, Alan Harvey, Simon Mackay, Andrew Paul, Robin Plevin

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Nuclear factor-kappa B (NF-κB) is a ubiquitous transcription factor found originally to play a key role in regulating inflammation. However considerable evidence links this pathway to the suppression of apoptosis, cellular transformation, proliferation and invasion (Aggarwal et al., 2006). Moreover, recent studies have also linked inflammation to cancer progression making NF-κB overall a promising therapeutic target for drug discovery (Dobrovolskaia & Kozlov, 2005). In this study we examined the effect of the natural product canthin-6-one (SU182) as part of a CRUK small molecule drug discovery programme for effects upon the NF-κB pathway. Initial studies demonstrated that SU182 was found to have good potency against the inhibitory kappa B kinases (IKKs) at 30M in vitro. However, at concentrations up to 30M, SU182 had no effect upon TNFα stimulated loss in cellular IκBα or p65 phosphorylation in the keratinocyte cell line NCTC2544. Nevertheless, 30M SU182 reduced TNF-α / PMA-induced NF-κB-linked luciferase reporter activity to (22.9 ± 5%) and (34.6± 3 %, P<0.001) respectively, suggesting an action downstream of IKK signalling. Indeed, SU182 neither decreased NF-κB-DNA binding as assayed by EMSA nor prevented the translocation of p65 (NF-κB) to the nucleus assessed by immunofluorescence and subcellular fractionation. In addition to the inhibition of transcriptional activity of TNFα-induced NF-κB reporter activity SU182 significantly reduced PMA-induced AP-1-linked luciferase reporter activity to about (48± 9% at 30M, P<0.001) . This mode of inhibition was not sufficient to prevent the activation of NF-κB dependent induction of other proteins such as COX-2 and iNOS, or activated MAP kinases (p38, JNK and ERK1/2) in LPS stimulated RAW 264.7 macrophages. Taken together these data indicate the potential for SU182 to interfere with the transcription factors NF-κB and AP-1 at transcriptional level. However, no potential anti-inflammatory effect was indicated, further investigation for other NF-κB dependent proteins linked to survival are also required to identify the exact mechanism of action.

Keywords: Canthin-6-one, NF-κB, AP-1, phosphorylation, Nuclear translocation, DNA-binding activity, inflammatory proteins.

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Authors: Rachel Buchanan, Rebecca LaRiviere

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Context: The ongoing effects of colonialism continue to be experienced through paternalistic policies and funding processes that cause disjuncture between and across Indigenous early childhood programming on-reserve and in urban and Northern settings in Canada. While various educational organizations and social service providers have risen to address these challenges in the short, medium and long term, there continues to be a lack in nation-wide cohesive, culturally grounded, and meaningful early learning programming for Indigenous children in Canada. Indigenous-centered early learning programs tend to face one of two scaling dilemmas: their program goals are too prescriptive to enable the program to be meaningfully replicated in different cultural/ community settings, or their program goals are too broad to be meaningfully adapted to the unique cultural and contextual needs and desires of Indigenous communities (the “franchise approach”). There are over 600 First Nations communities in Canada representing more than 50 Nations and languages. Consequently, Indigenous early learning programming cannot be applied with a universal or “one size fits all” approach. Sustainable and comprehensive programming must be responsive to each community context, building upon existing strengths and assets to avoid program duplication and irrelevance. Thesis: Community-driven and culturally adapted early childhood programming is critical but cannot be achieved on a large scale within traditional program models that are constrained by prescriptive overarching program goals. Principles, rather than goals, are an effective way to navigate and evaluate complex and dynamic systems. Principles guide an intervention to be adaptable, flexible and scalable. The Martin Family Initiative (MFI) ’s Early Years program engages a principles-based approach to programming. As will be discussed in this paper, this approach enables the program to catalyze existing community-based strengths and organizational assets toward bridging gaps across and disjuncture between Indigenous early learning programs, as well as to scale programming in sustainable, context-responsive and dynamic ways. This paper argues that using a principles-driven and adaptive scaling approach, the Early Years model establishes important learnings for culturally adapted Indigenous early learning programming in Canada. Methodology: The Early Years has leveraged this approach to develop an array of programming with partner organizations and communities across the country. The Early Years began as a singular pilot project in one First Nation. In just three years, it has expanded to five different regions and community organizations. In each context, the program supports the partner organization through different means and to different ends, the extent to which is determined in partnership with each community-based organization: in some cases, this means supporting the organization to build home visiting programming from the ground-up; in others, it means offering organization-specific culturally adapted early learning resources to support the programming that already exists in communities. Principles underpin but do not define the practices of the program in each of these relationships. This paper will explore numerous examples of principles-based adaptability with the context of the Early Years, concluding that the program model offers theadaptability and dynamism necessary to respond to unique and ever-evolving community contexts and needs of Indigenous children today.

Keywords: culturally adapted programming, indigenous early learning, principles-based approach, program scaling

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Authors: Shanker Kalakotla, Krishna Mohan Gottumukkala

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Diabetes is a metabolic disorder characterized by hyperglycemia, carbohydrates, altered lipids and proteins metabolism. In recent research nanotechnology is a blazing field for the researchers; latterly there has been prodigious excitement in the nanomedicine and nano pharmacological area for the study of silver nanoparticles synthesis using natural products. Biological methods have been used to synthesize silver nanoparticles in presence of medicinally active antidiabetic plants, and this intention made us assess the biologically synthesized silver nanoparticles from the seed extract of Psoralea corylfolia using 1 mM silver nitrate solution. The synthesized herbal mediated silver nanoparticles (HMSNP’s) then subjected to various characterization techniques such as XRD, SEM, EDX, TEM, DLS, UV and FT-IR respectively. In current study, the silver nanoparticles tested for in-vitro anti-diabetic activity and possible toxic effects in healthy female albino mice by following OECD guidelines-425. Herbal mediated silver nanoparticles were successfully obtained from bioreduction of silver nitrate using Psoralea corylifolia plant extract. Silver nanoparticles have been appropriately characterized and confirmed using different types of equipment viz., UV-vis spectroscopy, XRD, FTIR, DLS, SEM and EDX analysis. From the behavioral observations of the study, the female albino mice did not show sedation, respiratory arrest, and convulsions. Test compounds did not cause any mortality at the dose level tested (i.e., 2000 mg/kg body weight) doses till the end of 14 days of observation and were considered safe. It may be concluded that LD50 of the HMSNPs was 2000mg/kg body weight. Since LD50 of the HMSNPs was 2000mg/kg body weight, so the preferred dose range for HMSNPs falls between the levels of 200 and 400 mg/kg. Further In-vivo pharmacological models and biochemical investigations will clearly elucidate the mechanism of action and will be helpful in projecting the currently synthesized silver nanoparticles as a therapeutic target in treating chronic ailments.

Keywords: herbal mediated silver nanoparticles, HMSNPs, toxicity of silver nanoparticles, PTP1B in-vitro anti-diabetic assay female albino mice, 425 OECD guidelines

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Authors: Serap Durkut, A. Eser Elcin, Y. Murat Elcin

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Stimuli-sensitive polymeric hydrogels have received extensive attention in the biomedical field due to their sensitivity to physical and chemical stimuli (temperature, pH, ionic strength, light, etc.). This study describes the rheological properties of a novel thermoresponsive poly(N-vinylcaprolactam)-g-collagen hydrogel. In the study, we first synthesized a facile and novel synthetic carboxyl group-terminated thermo-responsive poly(N-vinylcaprolactam)-COOH (PNVCL-COOH) via free radical polymerization. Further, this compound was effectively grafted with native collagen, by utilizing the covalent bond between the carboxylic acid groups at the end of the chains and amine groups of the collagen using cross-linking agent (EDC/NHS), forming PNVCL-g-Col. Newly-formed hybrid hydrogel displayed novel properties, such as increased mechanical strength and thermoresponsive characteristics. PNVCL-g-Col showed low critical solution temperature (LCST) at 38ºC, which is very close to the body temperature. Rheological studies determine structural–mechanical properties of the materials and serve as a valuable tool for characterizing. The rheological properties of hydrogels are described in terms of two dynamic mechanical properties: the elastic modulus G′ (also known as dynamic rigidity) representing the reversible stored energy of the system, and the viscous modulus G″, representing the irreversible energy loss. In order to characterize the PNVCL-g-Col, the rheological properties were measured in terms of the function of temperature and time during phase transition. Below the LCST, favorable interactions allowed the dissolution of the polymer in water via hydrogen bonding. At temperatures above the LCST, PNVCL molecules within PNVCL-g-Col aggregated due to dehydration, causing the hydrogel structure to become dense. When the temperature reached ~36ºC, both the G′ and G″ values crossed over. This indicates that PNVCL-g-Col underwent a sol-gel transition, forming an elastic network. Following temperature plateau at 38ºC, near human body temperature the sample displayed stable elastic network characteristics. The G′ and G″ values of the PNVCL-g-Col solutions sharply increased at 6-9 minute interval, due to rapid transformation into gel-like state and formation of elastic networks. Copolymerization with collagen leads to an increase in G′, as collagen structure contains a flexible polymer chain, which bestows its elastic properties. Elasticity of the proposed structure correlates with the number of intermolecular cross-links in the hydrogel network, increasing viscosity. However, at 8 minutes, G′ and G″ values sharply decreased for pure collagen solutions due to the decomposition of the elastic and viscose network. Complex viscosity is related to the mechanical performance and resistance opposing deformation of the hydrogel. Complex viscosity of PNVCL-g-Col hydrogel was drastically changed with temperature and the mechanical performance of PNVCL-g-Col hydrogel network increased, exhibiting lesser deformation. Rheological assessment of the novel thermo-responsive PNVCL-g-Col hydrogel, exhibited that the network has stronger mechanical properties due to both permanent stable covalent bonds and physical interactions, such as hydrogen- and hydrophobic bonds depending on temperature.

Keywords: poly(N-vinylcaprolactam)-g-collagen, thermoresponsive polymer, rheology, elastic modulus, stimuli-sensitive

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Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali

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A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

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Authors: Medani Prasad Rijal

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Forest itself is a factory as well as product. It supplies tangible and intangible goods and services. It supplies timber, fuel wood, fodder, grass leaf litter as well as non timber edible goods and medicinal and aromatic products additionally provides environmental services. These environmental services are of local, national or even global importance. In Nepal, more than 19 thousands community forests are providing environmental service in less economic benefit than actual efficiency. There is a risk of cost of management of those forest exceeds benefits and forests get converted to open access resources in future. Most of the environmental goods and services do not have markets which mean no prices at which they are available to the consumers, therefore the valuation of these services goods and services establishment of paying mechanism for such services and insure the benefit to community is more relevant in local as well as global scale. There are few examples of carbon trading in domestic level to meet the country wide emission goal. In this contest, the study aims to explore the public attitude towards carbon offsetting and their responsibility over service providers. This study helps in promotion of environment service awareness among general people, service provider and community forest. The research helps to unveil the carbon pool scenario in community forest and willingness to pay for carbon offsetting of people who are consuming more energy than general people and emitting relatively more carbon in atmosphere. The study has assessed the carbon pool status in two community forest and valuated carbon service from community forest through willingness to pay in Dharan municipality situated in eastern. In the study, in two community forests carbon pools were assessed following the guideline “Forest Carbon Inventory Guideline 2010” prescribed by Ministry of Forest and soil Conservation, Nepal. Final outcomes of analysis in intensively managed area of Hokse CF recorded as 103.58 tons C /ha with 6173.30 tons carbon stock. Similarly in Hariyali CF carbon density was recorded 251.72 mg C /ha. The total carbon stock of intensively managed blocks in Hariyali CF is 35839.62 tons carbon.

Keywords: carbon, offsetting, sequestration, valuation, willingness to pay

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Authors: Parikshit Gogo, N. N. Dutta

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The oxidative enzymes specially laccase (benzenediol: oxygen oxidoreductase, E.C.1.10.3.2) from bacteria, fungi and plants have been playing an important role in green technologies due to their specific advantageous properties. Laccase from different sources and in different forms was used as a biocatalyst in many oxidation and conjugation reactions starting from phenol to hydrocarbons. Tea polyphenols and its derivatives attract the scientific community because of their potential use as antioxidants in food, pharmaceutical and cosmetic industries. Conjugate of polyphenols emerged as a novel materials which shows better stability and antioxidant properties in applied fields. The conjugation reaction of catechin with poly (allylamine) has been studied using free, immobilized and cross-linked enzyme crystals (CLEC) of laccase from Trametes versicolor with particular emphasis on the effect of pertinent variables and kinetic aspects of the reaction. The stability and antioxidant property of the conjugated product was improved as compared to the unconjugated tea polyphenols. The reaction was studied in 11 different solvents in order to deduce the solvent effect through an attempt to correlate the initial reaction rate with solvent properties such as hydrophobicity (logP), water solubility (logSw), electron pair acceptance (ETN) and donation abilities (DNN), polarisibility and dielectric constant which exhibit reasonable correlations. The study revealed, in general that polar solvents favour the initial reaction rate. The kinetics of the conjugation reaction conformed to the so-called Ping-Pong-Bi-Bi mechanism with catechin inhibition. The stability as well as activity of the CLEC was better than the free enzymes and immobilized laccase for practical application. In case of immobilized laccase system marginal diffusional limitation could be inferred from the experimental data. The kinetic parameters estimated by non-linear regression analysis were found to be KmPAA(mM) = 0.75, 1.8967 and Kmcat (mM) = 11.769, 15.1816 for free and immobilized laccase respectively. An attempt has been made to assess the activity of the laccase for the conjugation reaction in relation to other reactions such as dimerisation of ferulic acids and develop a protocol to enhance polyphenol antioxidant activity.

Keywords: laccase, catechin, conjugation reaction, antioxidant properties

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