Search results for: dual inhibitors

Authors: Thomas Louis, Irina Primac, Florent Morfoisse, Tania Durre, Silvia Blacher, Agnes Noel

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In vitro and in vivo lymphangiogenesis assays are essential for the identification of potential lymphangiogenic agents and the screening of pharmacological inhibitors. In the present study, we analyse three biological models: in vitro lymphatic endothelial cell spheroids, in vivo ear sponge assay, and in vivo lymph node colonisation by tumour cells. These assays provide suitable 3D models to test pro- and anti-lymphangiogenic factors or drugs. 3D images were acquired by confocal laser scanning and light sheet fluorescence microscopy. Virtual scan microscopy followed by 3D reconstruction by image aligning methods was also used to obtain 3D images of whole large sponge and ganglion samples. 3D reconstruction, image segmentation, skeletonisation, and other image processing algorithms are described. Fixed and time-lapse imaging techniques are used to analyse lymphatic endothelial cell spheroids behaviour. The study of cell spatial distribution in spheroid models enables to detect interactions between cells and to identify invasion hierarchy and guidance patterns. Global measurements such as volume, length, and density of lymphatic vessels are measured in both in vivo models. Branching density and tortuosity evaluation are also proposed to determine structure complexity. Those properties combined with vessel spatial distribution are evaluated in order to determine lymphangiogenesis extent. Lymphatic endothelial cell invasion and lymphangiogenesis were evaluated under various experimental conditions. The comparison of these conditions enables to identify lymphangiogenic agents and to better comprehend their roles in the lymphangiogenesis process. The proposed methodology is validated by its application on the three presented models.

Keywords: 3D image segmentation, 3D image skeletonisation, cell invasion, confocal microscopy, ear sponges, light sheet microscopy, lymph nodes, lymphangiogenesis, spheroids

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Authors: Tarek M. Alguhane, Ayman H. Khalil, M. N. Fayed, Ayman M. Ismail

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A 15-storey RC building, studied in this paper, is representative of modern building type constructed in Madina City in Saudi Arabia before 10 years ago. These buildings are almost consisting of reinforced concrete skeleton, i. e. columns, beams and flat slab as well as shear walls in the stairs and elevator areas arranged in the way to have a resistance system for lateral loads (wind–earthquake loads). In this study, the dynamic properties of the 15-storey RC building were identified using ambient motions recorded at several spatially-distributed locations within each building. After updating the mathematical models for this building with the experimental results, three dimensional pushover analysis (nonlinear static analysis) was carried out using SAP2000 software incorporating inelastic material properties for concrete, infill and steel. The effect of modeling the building with and without infill walls on the performance point as well as capacity and demand spectra due to EQ design spectrum function in Madina area has been investigated. The response modification factor (R) for the 15 storey RC building is evaluated from capacity and demand spectra (ATC-40). The purpose of this analysis is to evaluate the expected performance of structural systems by estimating, strength and deformation demands in design, and comparing these demands to available capacities at the performance levels of interest. The results are summarized and discussed.

Keywords: seismic assessment, pushover analysis, ambient vibration, modal update

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Authors: Saurabh B. Ganorkar, Atul A. Shirkhedkar

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The need for investigations protecting against toxic impurities though seems to be a primary requirement; the impurities which may prove non - toxic can be explored for their therapeutic potential if any to assist advanced drug discovery. The essential role of pharmaceutical analysis can thus be extended effectively to achieve it. The present study successfully achieved these objectives with characterization of major degradation products as impurities for Zileuton which has been used for to treat asthma since years. The forced degradation studies were performed to identify the potential degradation products using Ultra-fine Liquid-chromatography. Liquid-chromatography-Mass spectrometry (Time of Flight) and Proton Nuclear Magnetic Resonance Studies were utilized effectively to characterize the drug along with five major oxidative and hydrolytic degradation products (DP’s). The mass fragments were identified for Zileuton and path for the degradation was investigated. The characterized DP’s were subjected to In-Silico studies as XP Molecular Docking to compare the gain or loss in binding affinity with 5-Lipooxygenase enzyme. One of the impurity of was found to have the binding affinity more than the drug itself indicating for its potential to be more bioactive as better Antiasthmatic. The close structural resemblance has the ability to potentiate or reduce bioactivity and or toxicity. The chances of being active biologically at other sites cannot be denied and the same is achieved to some extent by predictions for probability of being active with Prediction of Activity Spectrum for Substances (PASS) The impurities found to be bio-active as Antineoplastic, Antiallergic, and inhibitors of Complement Factor D. The toxicological abilities as Ames-Mutagenicity, Carcinogenicity, Developmental Toxicity and Skin Irritancy were evaluated using Toxicity Prediction by Komputer Assisted Technology (TOPKAT). Two of the impurities were found to be non-toxic as compared to original drug Zileuton. As the drugs are purposed and repurposed effectively the impurities can also be; as they can have more binding affinity; less toxicity and better ability to be bio-active at other biological targets.

Keywords: UFLC, LC-MS-TOF, NMR, Zileuton, impurities, toxicity, bio-activity

Procedia PDF Downloads 194

Authors: A. H. El-Shazly, A. El-Tayeb, M. F. Elkady, Mona G. E. Ibrahim, Abdelazim M. Negm

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In this paper, corona discharge plasma reactor was used for degradation of organic pollution in aqueous solutions in batch reactor. This work examines the possibility of increasing the organic pollution removal efficiency from wastewater using non-thermal plasma. Three types of organic pollution phenol, acid blue 25 and methylene blue are presented to investigate experimentally the amount of organic pollution removal efficiency from wastewater. Measurement results for phenol degradation percentage are 71% in 35 min and 96% when its residence time is 60 min. In addition, the degradation behavior of acid blue 25 utilizing dual pin-to-plate corona discharge plasma system displays a removal efficiency of 82% in 11 min. The complete decolorization was accomplished in 35 min for concentration of acid blue 25 up to 100 ppm. Furthermore, the methylene blue degradation touched up to 85% during 35 min treatment in corona discharge plasma a batch reactor system. The decolorization ratio, conductivity, corona current and discharge energy are considered at various concentration molarity for AlCl3, CaCl2, KCl and NaCl under different molar concentration. It was observed that the attendance of salts at the same concentration level considerably diminished the rate and the extent of decolorization. The research presented that the corona system could be positively utilized in a diversity of organically contaminated at diverse concentrations. Energy consumption requirements for decolorization was considered. The consequences will be valuable for designing the plasma treatment systems appropriate for industrial wastewaters.

Keywords: wastewater treatment, corona discharge, non-thermal plasma, organic pollution

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Authors: Vakamalla Teja Reddy, Narasimha Mangadoddy

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Hydrocyclones are used to separate particles into different size fractions in the mineral processing, chemical and metallurgical industries. High speed video imaging, Laser Doppler Anemometry (LDA), X-ray and Gamma ray tomography are previously used to measure the two-phase flow characteristics in the cyclone. However, investigation of solids flow characteristics inside the cyclone is often impeded by the nature of the process due to slurry opaqueness and solid metal wall vessels. In this work, a dual-plane high speed Electrical resistance tomography (ERT) is used to measure hydrocyclone internal flow dynamics in situ. Experiments are carried out in 3 inch hydrocyclone for feed solid concentrations varying in the range of 0-50%. ERT data analysis through the optimized FEM mesh size and reconstruction algorithms on air-core and solid concentration tomograms is assessed. Results are presented in terms of the air-core diameter and solids volume fraction contours using Maxwell’s equation for various hydrocyclone operational parameters. It is confirmed by ERT that the air core occupied area and wall solids conductivity levels decreases with increasing the feed solids concentration. Algebraic slip mixture based multi-phase computational fluid dynamics (CFD) model is used to predict the air-core size and the solid concentrations in the hydrocyclone. Validation of air-core size and mean solid volume fractions by ERT measurements with the CFD simulations is attempted.

Keywords: air-core, electrical resistance tomography, hydrocyclone, multi-phase CFD

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Authors: Raju Ranjha, Surbhi Aggarwal

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Background: Inflammation plays an important role in infectious and non-infectious diseases. MiRNA is also reported to play role in inflammation and associated cancers. Chemokine CXCL12 is also known to play role in inflammation and various cancers. CXCL12/CXCR4 chemokine axis was involved in pathogenesis of IBD specially UC. Supplementation of CXCL12 induces homing of dendritic cells to spleen and enhances control of plasmodium parasite in BALB/c mice. We looked at the regulation of CXCL12β by miRNA in UC colitis. Prolonged inflammation of colon in UC patient increases the risk of developing colorectal cancer. We looked at the expression differences of CXCl12β and its targeting miRNA in cancer susceptible area of colon of UC patients. Aim: Aim of this study was to find out the expression regulation of CXCL12β by miRNA in inflammation. Materials and Methods: Biopsy samples and blood samples were collected from UC patients and non-IBD controls. mRNA expression was analyzed using microarray and real-time PCR. CXCL12β targeting miRNA were looked by using online target prediction tools. Expression of CXCL12β in blood samples and cell line supernatant was analyzed using ELISA. miRNA target was validated using dual luciferase assay. Results and conclusion: We found miR-200a regulate the expression of CXCL12β in UC. Expression of CXCL12β was increased in cancer susceptible part of colon and expression of its targeting miRNA was decreased in the same part of colon. miR-200a regulate CXCL12β expression in inflammation and may be an important therapeutic target in inflammation associated cancer.

Keywords: inflammation, miRNA, regulation, CXCL12

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Authors: Yenny Paola Morales Cortés, Fabián Rico Rodríguez, Juan Carlos Serrato Bermúdez, Carlos Arturo Martínez Riascos

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Numerous benefits of galactooligosaccharides (GOS) as prebiotics have motivated the study of enzymatic processes for their production. These processes have special complexities due to several factors that make difficult high productivity, such as enzyme type, reaction medium pH, substrate concentrations and presence of inhibitors, among others. In the present work the production of galactooligosaccharides (with different degrees of polymerization: two, three and four) from lactose was studied. The study considers the formulation of a mathematical model that predicts the production of GOS from lactose using the enzyme β-galactosidase. The effect of pH in the reaction was studied. For that, phosphate buffer was used and with this was evaluated three pH values (6.0.6.5 and 7.0). Thus it was observed that at pH 6.0 the enzymatic activity insignificant. On the other hand, at pH 7.0 the enzymatic activity was approximately 27 times greater than at 6.5. The last result differs from previously reported results. Therefore, pH 7.0 was chosen as working pH. Additionally, the enzyme concentration was analyzed, which allowed observing that the effect of the concentration depends on the pH and the concentration was set for the following studies in 0.272 mM. Afterwards, experiments were performed varying the lactose concentration to evaluate its effects on the process and to generate the data for the adjustment of the mathematical model parameters. The mathematical model considers the reactions of lactose hydrolysis and transgalactosylation for the production of disaccharides and trisaccharides, with their inverse reactions. The production of tetrasaccharides was negligible and, because of that, it was not included in the model. The reaction was monitored by HPLC and for the quantitative analysis of the experimental data the Matlab programming language was used, including solvers for differential equations systems integration (ode15s) and nonlinear problems optimization (fminunc). The results confirm that the transgalactosylation and hydrolysis reactions are reversible, additionally inhibition by glucose and galactose is observed on the production of GOS. In relation to the production process of galactooligosaccharides, the results show that it is necessary to have high initial concentrations of lactose considering that favors the transgalactosylation reaction, while low concentrations favor hydrolysis reactions.

Keywords: β-galactosidase, galactooligosaccharides, inhibition, lactose, Matlab, modeling

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Authors: Latife Merve Oktay, Berrin Tugrul

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Hydroxytyrosol (HT) is a phenolic phytochemical molecule derived from the hydrolysis of oleuropein, which originates during the maturation of the olives. It has recently received particular attention because of its antioxidant, anti-proliferative, pro-apoptotic and anti-inflammatory activities. In this study, we investigated the cytotoxic and apoptotic effects of hydroxytyrosol and its effects on phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase 1/2 (ERK 1/2) signaling pathways in human ovarian cancer cell lines OVCAR-3 and MDAH-2774. XTT cell proliferation kit, Cell Death Detection Elisa Plus Kit (Roche) and Human Apoptosis Array (R&D Systems) were used to determine the cytotoxic and apoptotic effects of HT in OVCAR-3 and MDAH-2774 cell lines at 24, 48, 72, and 96 h. Effect of HT on PI3K/Akt and ERK 1/2 signaling pathways were investigated by using specific inhibitors of these pathways. IC50 values of HT were found to be 102.3 µM in MDAH-2774 cells at 72 h and 51.5 µM in OVCAR-3 cells at 96 h. Apoptotic effect of HT in MDAH-2774 cells was the highest at 50 µM at 72 h, and kept decreasing at 100 and 150 µM concentrations and was not seen at 200 µM and higher concentrations. Highest apoptotic effect was seen at 100 µM concentration in OVCAR-3 cells at 96 h, however apoptotic effect was decreased over 100 µM concentrations. According to antibody microarray results, HT increased the levels of pro-apoptotic molecules Bad, Bax, active caspase-3, Htra2/Omi by 2.0-, 1.4-, 1.2-, 4.2-fold, respectively and also increased the levels of pro-apoptotic death receptors TRAIL R1/DR4, TRAIL R2/DR5, FAS/TNFRSF6 by 2.1-, 1.7-, 1.6-fold, respectively, however, it decreased the level of Survivin by 1.6-fold which is one of the inhibitor of apoptosis protein (IAP) family in MDAH-2774 cells. In OVCAR-3 cells, HT decreased the levels of anti-apoptotic proteins Bcl-2, pro-caspase 3 by 3.1-, 8.2-fold, respectively and IAP family proteins CIAP-1, CIAP-2, XIAP, Livin, Survivin by 6.5-, 6.0-, 3.2-, 2.2-, 2.7-fold, respectively and increased the level of cytochrome-c by 1.2-fold. We have shown that HT shows its cytotoxic and apoptotic effect through inhibiting ERK 1/2 signaling pathway in both OVCAR-3 and MDAH-2774 cells. Further studies are needed to investigate molecular mechanisms and modulatory effects of hydroxytyrosol.

Keywords: apoptosis, cytotoxicity, hydroxytyrosol, ovarian cancer

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Authors: Abderrahmane Kechich, Othmane Abdelkhalek

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Static converters behave as nonlinear loads that inject harmonic currents into the grid and increase the consumption of the inactive power. On the other hand, the increased use of sensitive equipment requires the application of sinusoidal voltages. As a result, the electrical power quality control has become a major concern in the field of power electronics. In this context, the active power conditioner (UPQC) was developed. It combines both serial and parallel structures; the series filter can protect sensitive loads and compensate for voltage disturbances such as voltage harmonics, voltage dips or flicker when the shunt filter compensates for current disturbances such as current harmonics, reactive currents and imbalance. This double feature is that it is one of the most appropriate devices. Calculating parameters is an important step and in the same time it’s not easy for that reason several researchers based on trial and error method for calculating parameters but this method is not easy for beginners researchers especially what about the controller’s parameters, for that reason this paper gives a mathematical way to calculate of almost all of UPQC parameters away from trial and error method. This paper gives also a new approach for calculating of PI regulators parameters for purpose to have a stable UPQC able to compensate for disturbances acting on the waveform of line voltage and load current in order to improve the electrical power quality.

Keywords: UPQC, Shunt active filer, series active filer, PI controller, PWM control, dual-loop control

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Authors: Reda A. H. Mahmoud

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This paper investigates the pragmatic meaning of prosodic focus through four accentuation moods of blaming utterances in Egyptian Arabic. Prosodic focus results in various pragmatic meanings when the speaker utters the same blaming expression in different emotional moods: the angry, the mocking, the frustrated, and the informative moods. The main objective of this study is to interpret the meanings of these four accentuation moods in relation to their illocutionary forces and pre-locutionary effects, the integrated features of prosodic focus (e.g., tone movement distributions, pitch accents, lengthening of vowels, deaccentuation of certain syllables/words, and tempo), and the consonance between the former prosodic features and certain lexico-grammatical components to communicate the intentions of the speaker. The data on blaming utterances has been collected via elicitation and pre-recorded material, and the selection of blaming utterances is based on the criteria of lexical and prosodic regularity to be processed and verified by three computer programs, Praat, Speech Analyzer, and Spectrogram Freeware. A dual pragmatic approach is established to interpret expressive blaming utterance and their lexico-grammatical distributions into intonational focus structure units. The pragmatic component of this approach explains the variable psychological attitudes through the expressions of blaming and their effects whereas the analysis of prosodic focus structure is used to describe the intonational contours of blaming utterances and other prosodic features. The study concludes that every accentuation mood has its different prosodic configuration which influences the listener’s interpretation of the pragmatic meanings of blaming utterances.

Keywords: pragmatics, pragmatic interpretation, prosody, prosodic focus

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Authors: Diana La Forgia, Jean Baptiste Thibord, François Verheggen

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Volatiles Organic Compound (VOCs) are one of the many features of defense used by plants in their eternal fight against pests. Their main role is to attract the natural enemies of the herbivores. But on another hand, they can be used by the same herbivores to locate plants while foraging. In an attempt to fill a gap of knowledge in a complex web of interactions, we focused on wireworms (Coleoptera:Elateridae). Wireworms whose larvae feed on roots are one of the most spread pests of valuable crops such as maize and potatoes, causing important economical damage. Little is known about the root compounds that are playing a role in the attraction of the larvae. In order to know more about these compounds, we compared four different maize varieties (Zea mays mays) that are known to have different levels of attraction, from weak to strong, for wireworms in fields. We tested the attraction of larvae in laboratory conditions in dual-choice olfactometer assays where they were offered all possible combinations of the four maize varieties. Contemporary, we collected the VOCs of each variety during 24h using a push-and-pull system. The collected samples were then analyzed by gas chromatography coupled with a mass spectrometer (GC-MS) to identify their molecular profiles. The choice of the larvae was dependent on the offered combination and some varieties were preferred to others. Differences were also observed in terms of quantitative and qualitative emissions of volatile profiles between the maize varieties. Our aim is to develop traps based on VOCs from maize roots to open a new frontier in wireworms management.

Keywords: integrated pest management, maize roots, plant defense, volatile organic compounds, wireworms

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Authors: Agustinus Bandur, Dyah Budiastuti

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With the rapid development of information and communication technology (ICT) in globalisation era, higher education (HE) internationalisation has become a worldwide phenomenon. However, even though various studies have been widely published in existing literature, the settings of these studies were taken places in developed countries. Accordingly, the major purpose of this article is to explore the current trends of higher education internationalisation programs with particular reference to identify the benefits and challenges confronted by participating staff and students. For these purposes, ethnographic qualitative study with the usage of NVivo 11 software was applied in coding, analyzing, and visualization of non-numeric data gathered from interviews, videos, web contents, social media, and relevant documents. Purposive sampling technique was applied in this study with a total of ten high-ranked accredited government and private universities in Indonesia. On the basis of thematic and cross-case analyses, this study indicates that while Australia has led other countries in dual-degree programs, partner universities from Japan and Korea have the most frequent collaboration on student exchange programs. Meanwhile, most visiting scholars who have collaborated with the universities in this study came from the US, the UK, Japan, Australia, Netherlands, and China. Other European countries such as Germany, French, and Norway have also conducted joint research with Indonesian universities involved in this study. This study suggests that further supports of government policy and grants are required to overcome the challenges as well as strategic leadership and management roles to achieve high impacts of such programs on higher education quality.

Keywords: higher education, internationalisation, challenges, Indonesia

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Authors: Sukumar Namineni, Tracy O'Connor, Ulrich Kalinke, Percy Knolle, Mathias Heikenwaelder

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The liver is one of the pivotal organs in vertebrate animals, serving a multitude of functions such as metabolism, detoxification and protein synthesis and including a predominant role in innate immunity. The innate immune mechanisms pertaining to liver in controlling viral infections have largely been attributed to the Kupffer cells, the locally resident macrophages. However, all the cells of liver are equipped with innate immune functions including, in particular, the hepatocytes. Hence, our aim in this study was to elucidate the innate immune contribution of hepatocytes in viral clearance using mice lacking Ikkβ specifically in the hepatocytes, termed IkkβΔᴴᵉᵖ mice. Blockade of Ikkβ activation in IkkβΔᴴᵉᵖ mice affects the downstream signaling of canonical NF-κB signaling by preventing the nuclear translocation of NF-κB, an important step required for the initiation of innate immune responses. Interestingly, infection of IkkβΔᴴᵉᵖ mice with lymphocytic choriomeningitis virus (LCMV) led to strongly increased hepatic viral titers – mainly confined in clusters of infected hepatocytes. This was due to reduced interferon stimulated gene (ISG) expression during the onset of infection and a reduced CD8+ T-cell-mediated response. Decreased ISG production correlated with increased liver LCMV protein and LCMV in isolated hepatocytes from IkkβΔᴴᵉᵖ mice. A similar phenotype was found in LCMV-infected mice lacking interferon signaling in hepatocytes (IFNARΔᴴᵉᵖ) suggesting a link between NFkB and interferon signaling in hepatocytes. We also observed a failure of interferon-mediated inhibition of HBV replication in HepaRG cells treated with NF-kB inhibitors corroborating our initial findings with LCMV infections. Collectively, these results clearly highlight a previously unknown and influential role of hepatocytes in the induction of innate immune responses leading to viral clearance during a systemic viral infection with LCMV-WE.

Keywords: CD8+ T cell responses, innate immune mechanisms in the liver, interferon signaling, interferon stimulated genes, NF-kB signaling, viral clearance

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Authors: Samaneh Nazeri, Bagher Mojazi Amiri, Hamid Farahmand

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Production of high quality fish eggs with reasonable hatching rate makes a success in aquaculture industries. It is influenced by the environmental stimulators and inhibitors. Diazinon is a widely-used pesticide in Golestan province (Southern Caspian Sea, North of Iran) which is washed to the aquatic environment (3 mg/L in the river). It is little known about the effect of this pesticide on the embryogenesis of sturgeon fish, the valuable species of the Caspian Sea. Hormonal content of the egg is an important factor to guaranty the successful passes of embryonic stages. In this study, the fate of Persian sturgeon embryo to 24, 48, 72, and 96-hours exposure of diazinon (LC₅₀ dose) was tested. Also, the effect of thyroid hormones (T3 and T4) on these embryos was tested concurrently or separately with diazinon LC ₅₀ dose. Fertilized eggs are exposed to T3 (low dose: 1 ng/ml, high dose: 10 ng/ml), T4 (low dose: 1 ng/ml, high dose: 10 ng/ml). Six eggs were randomly selected from each treatment (with three replicates) in five developmental stages (two cell- division, neural, heart present, heart beaten, and hatched larvae). The possibility of changing T3, T4, and cortisol contents of the embryos were determined in all treated groups and in every mentioned embryonic stage. The hatching rate in treated groups was assayed at the end of the embryogenesis to clarify the effect of thyroid hormones and diazinon. The results indicated significant differences in thyroid hormone contents, but no significant differences were recognized in cortisol levels at various early life stages of embryos. There was also significant difference in thyroid hormones in (T3, T4) + diazinon treated embryos (P˂0.05), while no significant difference between control and treatments in cortisol levels was observed. The highest hatching rate was recorded in HT3 treatment, while the lowest hatching rate was recorded for diazinon LC₅₀ treatment. The result confirmed that Persian sturgeon embryo is less sensitive to diazinon compared to teleost embryos, and thyroid hormones may increase hatching rate even in the presence of diazinon.

Keywords: Persian sturgeon, diazinon, thyroid hormones, cortisol, embryo

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Authors: Blair D. Macdonald

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After nearly one hundred years of its origin, foundational quantum mechanics remains one of the greatest unexplained mysteries in physicists today. Within this time, chaos theory and its geometry, the fractal, has developed. In this paper, the propagation behaviour with an iteration of a simple fractal, the Koch Snowflake, was described and analysed. From an arbitrary observation point within the fractal set, the fractal propagates forward by oscillation—the focus of this study and retrospectively behind by exponential growth from a point beginning. It propagates a potentially infinite exponential oscillating sinusoidal wave of discrete triangle bits sharing many characteristics of light and quantum entities. The model's wave speed is potentially constant, offering insights into the perception and a direction of time where, to an observer, when travelling at the frontier of propagation, time may slow to a stop. In isolation, the fractal is a superposition of component bits where position and scale present a problem of location. In reality, this problem is experienced within fractal landscapes or fields where 'position' is only 'known' by the addition of information or markers. The quantum' measurement problem', 'uncertainty principle,' 'entanglement,' and the classical-quantum interface are addressed; these are a problem of scale invariance associated with isolated fractality. Dual forward and retrospective perspectives of the fractal model offer the opportunity for unification between quantum mechanics and cosmological mathematics, observations, and conjectures. Quantum and cosmological problems may be different aspects of the one fractal geometry.

Keywords: measurement problem, observer, entanglement, unification

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Authors: Yifat Koren Carmi, Abed Agbarya, Hazem Khamaisi, Raymond Farah, Yelena Shechtman, Roman Korobochka, Jacob Gopas, Jamal Mahajna

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Ovarian cancer (OC), the second most common form of gynecological malignancy, has a poor prognosis and is frequently identified in its late stages. The recommended treatment for OC typically includes a platinum-based chemotherapy, like carboplatin. Nonetheless, OC treatment has proven challenging due to toxicity and development of acquired resistance to therapy. Chemoresistance is a significant obstacle to a long-lasting response in OC patients, believed to arise from alterations within the cancer cells as well as within the tumor microenvironments (TME). Malignant ascites is a presenting feature in more than one-third of OC patients. It serves as a reservoir for a complex mixture of soluble factors, metabolites, and cellular components, providing a pro-inflammatory and tumor-promoting microenvironment for the OC cells. Malignant ascites is also associated with metastasis and chemoresistance. In an attempt to elucidate the role of TME in chemoresistance of OC, we monitored the ability of soluble factors derived from ascites fluids to affect platinum sensitivity of OC cells. This research, compared ascites fluids from non-malignant cirrhotic patients to those from OC patients in terms of their ability to alter the platinum sensitivity of OC cells. Our findings indicated that exposure to OC ascites induces platinum chemoresistance on OC cells in 11 out of 13 cases (85%). In contrast, 75% of cirrhosis ascites (3 out of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL-6, and to a lesser extent HGF were enriched in OC ascites, whereas IL-22 was enriched in cirrhosis ascites. Pharmaceutical inhibitors that target the IL-6/JAK signaling pathway were mildly effective in overcoming the platinum chemoresistance induced by malignant ascites. In contrast, Crizotinib an HGF/c-MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemoresistance to OC. Our findings demonstrate the importance of OC ascites in supporting platinum chemoresistance as well as the potential of a combination therapy with Crizotinib and the estradiol metabolite 2HE2 to regain OC cells chemosensitivity.

Keywords: ovarian cancer, platinum chemoresistance, malignant ascites, tumor microenvironment, IL-6, 2-hydroxyestradiol, HGF, crizotinib

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Authors: Seong Gu Hwang, Young Kyoon Oh, Joseph F. dela Cruz

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Marbling, or intramuscular fat, has been consistently identified as one of the top beef quality problems. Intramuscular adipocytes distribute throughout the perimysial connective tissue of skeletal muscle and are the major site for the deposition of intramuscular fat, which is essential for the eating quality of meat. The stromal vascular fraction of the skeletal muscle contains progenitor cells that can be enhanced to differentiate to adipocytes and increase intramuscular fat. Primary cultures of bovine intramuscular stromal vascular cells were used in this study to elucidate the effects of extracellular calcium and retinoic acid concentration on adipocyte differentiation. Cell viability assay revealed that even at different concentrations of calcium and retinoic acid, there was no significant difference on cell viability. Monitoring of the adipocyte differentiation showed that bovine intramuscular stromal vascular cells cultured in a low concentration of extracellular calcium and retinoic acid had a better degree of fat accumulation. The mRNA and protein expressions of PPARγ, C/EBPα, SREBP-1c and aP2 were analyzed and showed a significant upregulation upon the reduction in the level of extracellular calcium and retinoic acid. The upregulation of these adipogenic related genes means that the decreasing concentration of calcium and retinoic acid is able to stimulate the adipogenic differentiation of bovine intramuscular stromal vascular cells. To further elucidate the effect of calcium, the expression level of calreticulin was measured. Calreticulin which is known to be an inhibitor of PPARγ was down regulated by the decreased level of calcium and retinoic acid in the culture media. The same tendency was observed on retinoic acid receptors RARα and CRABP-II. These receptors are recognized as adipogenic inhibitors, and the downregulation of their expression allowed a better level of differentiation in bovine intramuscular stromal vascular cells. In conclusion, data show that decreasing the level of extracellular calcium and retinoic acid can significantly promote adipogenesis in intramuscular stromal vascular cells of Hanwoo beef cattle. These findings may provide new insights in enhancing intramuscular adipogenesis and marbling in beef cattle.

Keywords: calcium, calreticulin, hanwoo beef, retinoic acid

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Authors: Ahmed Elgharably, Nivien Nafady

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Arbuscular mycorrhizal fungi (AMF) and plant growth promoting microbes (PGPM) can promote plant growth under saline conditions. This study investigated how AMF and PGPM affected the growth and grain yield of wheat at different soil salinity levels (0, 75 and 150 mM NaCl). AMF colonization percentage, grain yield and dry weights and lengths of shoot and root, N, P K, Na, malondialdehyde, chlorophyll and proline contents and shoot relative permeability were determined. Salinity reduced NPK uptake and malondialdehyde and chlorophyll contents, and increased shoot Na concentration, relative permeability, and proline content, and thus declined plant growth. PGPM inoculation enhanced AMF colonization, P uptake, and K/Na ratio, but alone had no significant effect on plant growth and grain yield. AMF inoculation significantly enhanced NPK uptake, increased chlorophyll content and decreased shoot relative permeability, proline and Na contents, and thus promoted the plant growth. The inoculation of PGPM significantly enhanced the positive effects of AMF in controlling Na uptake and in increasing chlorophyll and NPK contents. Compared to AMF inoculation alone, dual inoculation with AMF and PGPM resulted in approximately 10, 25 and 25% higher grain yield at 0, 75 and 150 mM NaCl, respectively. The results provide that PGPM inoculation can maximize the effects of AMF inoculation in alleviating the deleterious effects of NaCl salts on wheat growth.

Keywords: mycorrhizal fungi, salinity, sodium, wheat

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Authors: Abhijit Trailokya, Kamlesh Patel

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Background: Hypertension is a common disease seen in clinical practice and is associated with high morbidity and mortality. Many patients require combination therapy for the management of hypertension. Objective: To evaluate co-morbidities, risk factors and management practices of hypertension in Indian population. Material and methods: A total of 1596 hypertensive adult patients received anti-hypertensive medications were studied in a cross-sectional, multi-centric, non-interventional, observational registry. Statistical analysis: Categories or nominal data was expressed as numbers with percentages. Continuous variables were analyzed by descriptive statistics using mean, SD, and range Chi square test was used for in between group comparison. Results: The study included 73.50% males and 26.50% females. Overweight (50.50%) and obesity (30.01%) was common in the hypertensive patients (n=903). A total of 54.76% patients had history of smoking. Alcohol use (33.08%), sedentary life style (32.96%) and history of tobacco chewing (17.92%) were the other lifestyle habits of hypertensive patients. Diabetes (36.03%) and dyslipidemia (39.79%) history was common in these patients. Family history of hypertension and diabetes was seen in 82.21% and 45.99% patients respectively. Most (89.16%) patients were treated with combination of antihypertensive agents. ARBs were the by far most commonly used agents (91.98%) followed by calcium channel blockers (68.23%) and diuretics (60.21%). ARB was the most (80.35%) preferred agent as monotherapy. ARB was also the most common agent as a component of dual therapy, four drug and five drug combinations. Conclusion: Most of the hypertensive patients need combination treatment with antihypertensive agents. ARBs are the most preferred agents as monotherapy for the management of hypertension. ARBs are also very commonly used as a component of combination therapy during hypertension management.

Keywords: antihypertensive, hypertension, management, ARB

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Authors: Saurabh Satija, Munish Garg

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Present work reports an efficient extraction method using microwaves based solvent–sample duo-heating mechanism, for the extraction of an important anti-diabetic plant Tinospora cordifolia from AYUSH system for estimation of berberine content. The process is based on simultaneous heating of sample matrix and extracting solvent under microwave energy. Methanol was used as the extracting solvent, which has excellent berberine solubilizing power and warms up under microwave attributable to its great dispersal factor. Extraction conditions like time of irradition, microwave power, solute-solvent ratio and temperature were optimized using Taguchi design and berberine was quantified using high performance thin layer chromatography. The ranked optimized parameters were microwave power (rank 1), irradiation time (rank 2) and temperature (rank 3). This kind of extraction mechanism under dual heating provided choice of extraction parameters for better precision and higher yield with significant reduction in extraction time under optimum extraction conditions. This developed extraction protocol will lead to extract higher amounts of berberine which is a major anti-diabetic moiety in Tinospora cordifolia which can lead to development of cheaper formulations of the plant Tinospora cordifolia and can help in rapid prevention of diabetes in the world.

Keywords: berberine, microwave, optimization, Taguchi

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Authors: S. V. Patil, P. S. Dounde, S. S. Patil

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Emulgels have emerged as one of the most interesting topical delivery system as it has dual release control system that is gel and emulsion. The major objective behind this formulation is delivery of hydrophobic drugs to systemic circulation via skin. In fact presence of a gelling agent in water phase converts a classical emulsion in to emulgel. The emulgel for dermatological use has several favorable properties such as being thixotropic, greaseless, easily spreadable, easily removable, emollient, non-staining, water-soluble, longer shelf life, bio-friendly, transparent and pleasing appearance. Various penetration enhancers can potentiate the effect. So this can be used as better topical drug delivery systems over present conventional systems available in market. Piroxicam is a non-steroidal anti-inflammatory drug that has major problems when administered orally; it is an insoluble drug and has irritant effect on gastro intestinal tract lead to ulceration and bleeding. The aim of this study was to overcoming these problems through preparation of topical emulgel of this drug. Emulgel of Piroxicam was prepared using Carbopol 940 along with mentha oil and clove oil as permeation enhancer. The prepared emulgel were evaluated for their physical appearance, pH determination, viscosity, spreadability, in vitro drug release, ex vivo permeation studies. All the prepared formulations showed acceptable physical properties, homogeneity, consistency, spreadability, viscosity and pH value. The emulgel was found to be stable with respect to physical appearance, pH, rheological properties and drug content at all temperature and conditions for three month.

Keywords: emulgel, piroxicam, menthe oil, clove oil

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Authors: Chiao-Chen Chang, Yang-Chieh Chin

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The mobile phone has no longer confined to communication, from the aspect of smartphones, consumers are only willing to pay for the product which the added value has corresponded with their appetites, such as multiple application, upgrade of the camera, and the appearance of the phone and so on. Moreover, as the maturity stage of smartphone industry today, the strategy which manufactures used to gain competitive advantages through hardware as well as software differentiation, is no longer valid. Thus, this research aims to initiate from brand image, to examine exactly whether consumers’ buying intention focus on smartphone brand or operating system, at the same time, perceived value and customer satisfaction will be added between brand image and continuous usage intention to investigate the impact of these two facets toward continuous usage intention. This study verifies the correlation, fitness, and relationship between the variables that lies within the conceptual framework. The result of using structural equation modeling shows that brand image has a positive impact on continuous usage intention. Firms can affect consumer perceived value and customer satisfaction through the creation of the brand image. It also shows that the brand image of smartphone and brand image of the operating system have a positive impact on customer perceived value and customer satisfaction. Furthermore, perceived value also has a positive impact on satisfaction, and so is the relation within satisfaction and perceived value to the continuous usage intention. Last but not least, the brand image of the smartphone has a more remarkable impact on customers than the brand image of the operating system. In addition, this study extends the results to management practice and suggests manufactures to provide fine product design and hardware.

Keywords: smartphone, brand image, perceived value, continuous usage intention

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Authors: Aida Rafat, Ramazan Kahraman, Mert Atilhan

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The aggressive corrosion behavior of conventional amine solvents is one of main barriers against large scale commerizaliation of amine absorption process for carbon capture application. Novel CO2 absorbents that exhibit minimal corrosivity against operation conditions are essential to lower corrosion damage and control and ensure more robustness in the capture plant. This work investigated corrosion behavior of carbon steel CS1018 in various CO2 absrobent solvents. The tested solvents included the classical amines MEA, DEA and MDEA, piperazine activated solvents MEA/PZ, MDEA/PZ and MEA/MDEA/PZ as well as mixtures of MEA and Room Temperature Ionic Liquids RTIL, namely MEA/[C4MIM][BF4] and MEA/[C4MIM][Otf]. Electrochemical polarization technique was used to determine the system corrosiveness in terms of corrosion rate and polarization behavior. The process parameters of interest were CO2 loading and solution temperature. Electrochemical resulted showed corrosivity order of classical amines at 40°C is MDEA> MEA > DEA wherase at 80°C corrosivity ranking changes to MEA > DEA > MDEA. Corrosivity rankings were mainly governed by CO2 absorption capacity at the test temperature. Corrosivity ranking for activated amines at 80°C was MEA/PZ > MDEA/PZ > MEA/MDEA/PZ. Piperazine addition seemed to have a dual advanatge in terms of enhancing CO2 absorption capacity as well as nullifying corrosion. For MEA/RTIL mixtures, the preliminary results showed that the partial repalcement of aqueous phase in MEA solution by the more stable nonvolatile RTIL solvents reduced corrosion rates considerably.

Keywords: corrosion, amines, CO2 capture, piperazine, ionic liquids

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Authors: Jason Ting Jing Cheng, Lee Foo Wei, Yew Ming Kun, Chin Ren Jie, Yip Chun Chieh

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The utilization of industrial by-products, such as steel slag in cementitious materials, not only mitigates environmental impact but also enhances material properties. This study investigates the dual influence of steel slag particle size on the compressive strength and carbonation efficiency of cementitious composites. Through a systematic experimental approach, steel slag particles were incorporated into cement at varying sizes, and the resulting composites were subjected to mechanical and carbonation tests. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX) are conducted in this paper. The findings reveal a positive correlation between increased particle size and compressive strength, attributed to the improved interfacial transition zone and packing density. Conversely, smaller particle sizes exhibited enhanced carbonation efficiency, likely due to the increased surface area facilitating the carbonation reaction. The presence of higher silica and calcium content in finer particles was confirmed by EDX, which contributed to the accelerated carbonation process. This study underscores the importance of particle size optimization in designing sustainable cementitious materials with balanced mechanical performance and carbon sequestration potential. The insights gained from the advanced analytical techniques offer a comprehensive understanding of the mechanisms at play, paving the way for the strategic use of steel slag in eco-friendly construction practices.

Keywords: steel slag, carbonation efficiency, particle size enhancement, compressive strength

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Authors: Laribi-Habchi Hasiba, Bouanane-Darenfed Amel, Drouiche Nadjib, Pausse André, Mameri Nabil

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Chitin, a linear 1, 4-linked N-acetyl-d-glucosamine (GlcNAc) polysaccharide is the major structural component of fungal cell walls, insect exoskeletons and shells of crustaceans. It is one of the most abundant naturally occurring polysaccharides and has attracted tremendous attention in the fields of agriculture, pharmacology and biotechnology. Each year, a vast amount of chitin waste is released from the aquatic food industry, where crustaceans (prawn, crab, Shrimp and lobster) constitute one of the main agricultural products. This creates a serious environmental problem. This linear polymer can be hydrolyzed by bases, acids or enzymes such as chitinase. In this context an extracellular chitinase (ChiA-65) was produced and purified from a newly isolated LHH100. Pure protein was obtained after heat treatment and ammonium sulphate precipitation followed by Sephacryl S-200 chromatography. Based on matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF/MS) analysis, the purified enzyme is a monomer with a molecular mass of 65,195.13 Da. The sequence of the 27 N-terminal residues of the mature ChiA-65 showed high homology with family-18 chitinases. Optimal activity was achieved at pH 4 and 75◦C. Among the inhibitors and metals tested p-chloromercuribenzoic acid, N-ethylmaleimide, Hg2+ and Hg + completelyinhibited enzyme activity. Chitinase activity was high on colloidal chitin, glycol chitin, glycol chitosane, chitotriose and chitooligosaccharide. Chitinase activity towards synthetic substrates in the order of p-NP-(GlcNAc) n (n = 2–4) was p-NP-(GlcNAc)2> p-NP-(GlcNAc)4> p-NP-(GlcNAc)3. Our results suggest that ChiA-65 preferentially hydrolyzed the second glycosidic link from the non-reducing end of (GlcNAc) n. ChiA-65 obeyed Michaelis Menten kinetics the Km and kcat values being 0.385 mg, colloidal chitin/ml and5000 s−1, respectively. ChiA-65 exhibited remarkable biochemical properties suggesting that this enzyme is suitable for bioconversion of chitin waste.

Keywords: Bacillus licheniformis LHH100, characterization, extracellular chitinase, purification

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Authors: Isra Elfatih Salih Edrees, Mehmet Serdar Ufuk Türeli

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In this paper, an energy-aware method is presented, integrating energy-efficient relay-augmented techniques for correlated data routing with the goal of optimizing bottleneck throughput in wireless sensor networks. The system tackles the dual challenge of throughput optimization while considering sensor network energy consumption. A unique routing metric has been developed to enable throughput maximization while minimizing energy consumption by utilizing data correlation patterns. The paper introduces a game theoretic framework to address the NP-complete optimization problem inherent in throughput-maximizing correlation-aware routing with energy limitations. By creating an algorithm that blends energy-aware route selection strategies with the best reaction dynamics, this framework provides a local solution. The suggested technique considerably raises the bottleneck throughput for each source in the network while reducing energy consumption by choosing the best routes that strike a compromise between throughput enhancement and energy efficiency. Extensive numerical analyses verify the efficiency of the method. The outcomes demonstrate the significant decrease in energy consumption attained by the energy-efficient relay-augmented bottleneck throughput maximization technique, in addition to confirming the anticipated throughput benefits.

Keywords: correlated data aggregation, energy efficiency, game theory, relay-augmented routing, throughput maximization, wireless sensor networks

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Authors: Ya-Ju Ju, Li-Chen Yang, Yi-Chun Du, Rong-Ju Cherng

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Introduction: It is estimated that 5-6% of school-aged children may be diagnosed to have developmental coordination disorder (DCD). Children with DCD are characterized with motor skill difficulty which cannot be explained by any medical or intellectual reasons. Such motor difficulties limit children’s participation to sports activity, further affect their physical fitness, cardiopulmonary function and balance, and may lead to obesity. The purpose of the project was to develop an exergaming system for children with DCD aiming to improve their physical fitness, cardiopulmonary function and balance ability. Methods: This study took five steps to build up the system: system planning, tasks selection, tasks programming, system integration and usability test. The system basically adopted virtual reality technique to integrate self-developed training programs. The training programs were developed to brainstorm among team members and after literature review. The selected tasks for training in the system were a combination of fundamental movement tor skill. Results and Discussion: Based on the theory of motor development, we design the training task from easy ones to hard ones, from single tasks to dual tasks. The tasks included walking, sit to stand, jumping, kicking, weight shifting, side jumping and their combination. Preliminary study showed that the tasks presented an order of development. Further study is needed to examine its effect on motor skill and cardiovascular fitness in children with DCD.

Keywords: virtual reality, virtual reality system, developmental coordination disorder, children

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Authors: Mohammed Sani Abdulai

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Ghana’s Public Financial Management reforms have been going on for some two decades now (1997/98 to 2017/18). Given this long period of reforms, Ghana in 2019 is putting together both a Public Financial Management (PFM) strategy and a Ghana Integrated Financial Management Information System (GIFMIS) strategy for the next 5-years (2020-2024). The primary aim of these dual strategies is assisting the country in moving beyond reforms to consolidation and sustainability. In this paper we, first, examined the evolution of Ghana’s PFM reforms. We, secondly, reviewed the legal and institutional reforms undertaken to strengthen the country’s key PFM institutions. Thirdly, we summarized the strengths and weaknesses identified by the 2018 Public Expenditure and Financial Accountability (PEFA) assessment of Ghana’s PFM system relating to its macro-fiscal framework, budget preparation and approval, budget execution, accounting and fiscal reporting as well as external scrutiny and audit. We, finally, considered what the country should be doing to achieve its intended goal of PFM consolidation and sustainability. Using a qualitative method of review and analysis of existing documents, we, through this paper, brought to the fore the lessons that could be learnt by other developing countries from Ghana’s PFM reforms experiences. These lessons included the need to: (a) undergird any PFM reform with a comprehensive PFM reform strategy; (b) undertake a legal and institutional reforms of the key PFM institutions; (c) assess the strengths and weaknesses of those reforms using PFM performance evaluation tools such as PEFA framework; and (d) move beyond reforms to consolidation and sustainability.

Keywords: public financial management, public expenditure and financial accountability, reforms, consolidation, sustainability

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Authors: Charlene N. T. Mfangnia, Henri E. Z. Tonnang, Berge Tsanou, Jeremy Herren

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Microsporidia MB is a recently discovered symbiont capable of blocking the transmission of Plasmodium from mosquitoes to humans. The symbiont can spread both horizontally and vertically among the mosquito population. This dual transmission gives the symbiont the ability to invade the mosquito population. The replacement of the mosquito population by the population of symbiont-infected mosquitoes then appears as a promising strategy for malaria control. In this context, the present study uses differential equations to model the transmission dynamics of Microsporidia MB in the population of female Anopheles mosquitoes. Long-term propagation scenarios of the symbiont, such as extinction, persistence or total infection, are obtained through the determination of the target and basic reproduction numbers, the equilibria, and the study of their stability. The stability is illustrated numerically, and the contribution of vertical and horizontal transmission in the spread of the symbiont is assessed. Data obtained from laboratory experiments are then used to explain the low prevalence observed in nature. The study also shows that the male death rate, the mating rate and the attractiveness of MB-positive mosquitoes are the factors that most influence the transmission of the symbiont. In addition, the introduction of temperature and the study of bifurcations show the significant influence of the environmental condition in the propagation of Microsporidia MB. This finding proves the necessity of taking into account environmental variables for the potential establishment of the symbiont in a new area.

Keywords: differential equations, stability analysis, malaria, microsporidia MB, horizontal transmission, vertical transmission, numerical illustration

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Authors: A.L. Tamm, N. Šott, J. Jürimäe, E. Lätt, A. Orav, Ü. Parm

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Coffee is one of the most frequently consumed beverages in the world but still its effects on human organism are not completely understood. Coffee has also been used as a method for weight loss, but its effectiveness has not been proved. There is also not similar comprehension in classifying overweight in choosing between body mass index (BMI) and fat percentage (fat%). The aim of the study was to determine associations between coffee consumption and body composition. Secondly, to detect which measure (BMI or fat%) is more accurate to use describing overweight. Altogether 103 persons enrolled the study and divided into three groups: coffee non-consumers (n=39), average coffee drinkers, who consumed 1 to 4 cups (1 cup = ca 200ml) of coffee per day (n=40) and excessive coffee consumers, who drank at least five cups of coffee per day (n=24). Body mass (medical electronic scale, A&D Instruments, Abingdon, UK) and height (Martin metal anthropometer to the nearest 0.1 cm) were measured and BMI calculated (kg/m2). Participants´ body composition was detected with dual energy X-ray absorptiometry (DXA, Hologic) and general data (history of chronic diseases included) and information about coffee consumption, and physical activity level was collected with questionnaires. Results of the study showed that excessive coffee consumption was associated with increased fat-free mass. It could be foremost due to greater physical activity level in school time or greater (not significant) male proportion in excessive coffee consumers group. For estimating the overweight the fat% in comparison to BMI recommended, as it gives more accurate results evaluating chronical disease risks. In conclusion coffee consumption probably does not affect body composition and for estimating the body composition fat% seems to be more accurate compared with BMI.

Keywords: body composition, body fat percentage, body mass index, coffee consumption

Procedia PDF Downloads 420