Search results for: small molecule inhibitor

Authors: S. D. N. K. Bathige, G. I. Godahewa, Navaneethaiyer Umasuthan, Jehee Lee

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Kunitz-type serine protease inhibitors (KTIs) are identified in various organisms including animals, plants and microbes. These proteins shared single or multiple Kunitz inhibitory domains link together or associated with other types of domains. Characteristic Kunitz type domain composed of around 60 amino acid residues with six conserved cysteine residues to stabilize by three disulfide bridges. KTIs are involved in various physiological processes, such as ion channel blocking, blood coagulation, fibrinolysis and inflammation. In this study, two Kunitz-type domain containing protein was identified from rock bream database and designated as RbKunitz. The coding sequence of RbKunitz encoded for 507 amino acids with 56.2 kDa theoretical molecular mass and 5.7 isoelectric point (pI). There are several functional domains including MANEC superfamily domain, PKD superfamily domain, and LDLa domain were predicted in addition to the two characteristic Kunitz domain. Moreover, trypsin interaction sites were also identified in Kunitz domain. Homology analysis revealed that RbKunitz shared highest identity (77.6%) with Takifugu rubripes. Completely conserved 28 cysteine residues were recognized, when comparison of RbKunitz with other orthologs from different taxonomical groups. These structural evidences indicate the rigidity of RbKunitz folding structure to achieve the proper function. The phylogenetic tree was constructed using neighbor-joining method and exhibited that the KTIs from fish and non-fish has been evolved in separately. Rock bream was clustered with Takifugu rubripes. The SYBR Green qPCR was performed to quantify the RbKunitz transcripts in different tissues and challenged tissues. The mRNA transcripts of RbKunitz were detected in all tissues (muscle, spleen, head kidney, blood, heart, skin, liver, intestine, kidney and gills) analyzed and highest transcripts level was detected in gill tissues. Temporal transcription profile of RbKunitz in rock bream blood tissues was analyzed upon LPS (lipopolysaccharide), Poly I:C (Polyinosinic:polycytidylic acid) and Edwardsiella tarda challenge to understand the immune responses of this gene. Compare to the unchallenged control RbKunitz exhibited strong up-regulation at 24 h post injection (p.i.) after LPS and E. tarda injection. Comparatively robust expression of RbKunits was observed at 3 h p.i. upon Poly I:C challenge. Taken together all these data indicate that RbKunitz may involve into to immune responses upon pathogenic stress, in order to protect the rock bream.

Keywords: Kunitz-type, rock bream, immune response, serine protease inhibitor

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Authors: Di Han, Lingfeng Li, Peixue Zhang, Yuzhuo Zhang

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Since natural gas extracted from the wellhead of a gas well, after passing through the throttle valve, causes a rapid decrease in temperature along with a decrease in pressure, which creates conditions for hydrate generation. In order to solve the problem of hydrate generation in the process of wellhead gathering, effective measures should be taken to prevent hydrate generation. In this paper, we firstly introduce the principle of natural gas throttling temperature drop and the theoretical basis of hydrate inhibitor injection calculation, and then use HYSYS software to simulate and calculate the three processes and determine the key process parameters. The hydrate control process applicable to the skid design of natural gas wellhead gathering skids was determined by comparing the hydrate control effect, energy consumption of key equipment and process adaptability.

Keywords: natural gas, hydrate control, skid design, HYSYS

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Authors: Gabriela D. Silva, Rodrigo L. O. R. Cunha, Mauricio D. Coutinho-Neto

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In the last four decades the biological activities of selenium compounds has received great attention, particularly for hypervalent derivates from selenium (IV) used as enzyme inhibitors. The unregulated activity of cysteine proteases are related to the development of several pathologies, such as neurological disorders, cardiovascular diseases, obesity, rheumatoid arthritis, cancer and parasitic infections. These enzymes are therefore a valuable target for designing new small molecule inhibitors such as selenuranes. Even tough there has been advances in the synthesis and design of new selenuranes based inhibitors, little is known about their mechanism of action. It is a given that inhibition occurs through the reaction between the thiol group of the enzyme and the chalcogen atom. However, several open questions remain about the nature of the mechanism (associative vs. dissociative) and about the nature of the reactive species in solution under physiological conditions. In this work we performed a theoretical investigation on model systems to study the possible routes of substitution reactions. Nucleophiles may be present in biological systems, our interest is centered in the thiol groups from the cysteine proteases and the hydroxyls from the aqueous environment. We therefore expect this study to clarify the possibility of a route reaction in two stages, the first consisting of the substitution of chloro atoms by hydroxyl groups and then replacing these hydroxyl groups per thiol groups in selenuranes. The structures of selenuranes and nucleophiles were optimized using density function theory along the B3LYP functional and a 6-311+G(d) basis set. Solvent was treated using the IEFPCM method as implemented in the Gaussian 09 code. Our results indicate that hydrolysis from water react preferably with selenuranes, and then, they are replaced by the thiol group. It show the energy values of -106,0730423 kcal/mol for dople substituition by hydroxyl group and 96,63078511 kcal/mol for thiol group. The solvatation and pH reduction promotes this route, increasing the energy value for reaction with hydroxil group to -50,75637672 kcal/mol and decreasing the energy value for thiol to 7,917767189 kcal/mol. Alternative ways were analyzed for monosubstitution (considering the competition between Cl, OH and SH groups) and they suggest the same route. Similar results were obtained for aliphatic and aromatic selenuranes studied.

Keywords: chalcogenes, computational study, cysteine proteases, enzyme inhibitors

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Authors: Somayeh Khanjani, Samaneh Nabavi, Shirin Jalili, Afshin Khara

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Fingerprints are area source of ubiquitous evidence and consequential for establishing identity. The detection and subsequent development of fingerprints are thus inevitable in criminal investigations. This becomes a difficult task in the case of certain extreme conditions like fire. A fire scene may be accidental or arson. The evidence subjected to fire is generally overlooked as there is a misconception that they are damaged. There are several scientific approaches to determine whether the fire was deliberate or not. In such as scenario, fingerprints may be most critical to link the perpetrator to the crime. The reason for this may be the destructive nature of fire. Fingerprints subjected to fire are exposed to high temperatures, soot deposition, electromagnetic radiation, and subsequent water force. It is believed that these phenomena damage the fingerprint. A novel fluorescent and a pre existing small particle reagent were investigated for the same. Zinc carbonates based fluorescent small particle reagent was capable of developing latent fingerprints exposed to a maximum temperature of 800 ̊C. Fluorescent SPR may prove very useful in such cases. Fluorescent SPR reagent based on zinc carbonate is a potential method for developing fingerprints from arson sites. The method is cost effective and non hazardous. This formulation is suitable for developing fingerprints exposed to fire/ arson.

Keywords: fingerprint, small particle reagent (SPR), arson, novel fluorescent

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Authors: N. Garrós, P. Bustos, N. Beirampour, R. Mohammadi, M. Mallandrich, A.C. Calpena, H. Colom

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Atopic dermatitis (AD) is a persistent skin condition characterized by chronic inflammation caused by an autoimmune response. It is a prevalent clinical issue that requires continual treatment to enhance the patient's quality of life. Systemic therapy often involves the use of glucocorticoids or immunosuppressants to manage symptoms. Our objective was to create and assess topical liposomal formulations containing Baricitinib (BNB), a reversible inhibitor of Janus-associated kinase (JAK), which is involved in various immune responses. These formulations were intended to address flare-ups and improve treatment outcomes for AD. We created three distinct liposomal formulations by combining different amounts of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine (POPC), cholesterol (CHOL), and ceramide (CER): (i) pure POPC, (ii) POPC mixed with CHOL (at a ratio of 8:2, mol/mol), and (iii) POPC mixed with CHOL and CER (at a ratio of 3.6:2.4:4.0 mol/mol/mol). We conducted various tests to determine the formulations' skin tolerance, irritancy capacity, and their ability to cause erythema and edema on altered skin. We also assessed the transepidermal water loss (TEWL) and skin hydration of rabbits to evaluate the efficacy of the formulations. Histological analysis, the HET-CAM test, and the modified Draize test were all used in the evaluation process. The histological analysis revealed that liposome POPC and POPC:CHOL avoided any damage to the tissues structures. The HET-CAM test showed no irritation effect caused by any of the three liposomes, and the modified Draize test showed a good Draize score for erythema and edema. Liposome POPC effectively counteracted the impact of xylol on the skin, and no erythema or edema was observed during the study. TEWL values were constant for all the liposomes with similar values to the negative control (within the range 8 - 15 g/h·m2, which means a healthy value for rabbits), whereas the positive control showed a significant increase. The skin hydration values were constant and followed the trend of the negative control, while the positive control showed a steady increase during the tolerance study. In conclusion, the developed formulations containing BNB exhibited no harmful or irritating effects, they did not demonstrate any irritant potential in the HET-CAM test and liposomes POPC and POPC:CHOL did not cause any structural alteration according to the histological analysis. These positive findings suggest that additional research is necessary to evaluate the efficacy of these liposomal formulations in animal models of the disease, including mutant animals. Furthermore, before proceeding to clinical trials, biochemical investigations should be conducted to better understand the mechanisms of action involved in these formulations.

Keywords: baricitinib, HET-CAM test, histological study, JAK inhibitor, liposomes, modified draize test

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Authors: Mariana Panayotova-Pencheva, Anetka Trifonova, Vassilena Dakova

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790 lungs from brown hares (Lepus europeus L.) from different regions of Bulgaria were investigated during the period 2009-2017. The parasitological status and pathomorphological features in the lungs were recorded. The following parasite species were established: one nematode - Protostrongylus tauricus (7.59% prevalence), one tapeworm – larva of Taenia pisiformis – Cysticercus pisiformis (3.04% prevalence) and one arthropod – larva of Linguatula serrata – Pentastomum dentatum (0.89% prevalence). Macroscopic lesions in the lungs were different depending on the causative agents. The infections with C. pisiformis and P. dentatum were attended with small, mainly superficial changes in the lungs. Protostrongylid infections were connected with different in appearance and burden macroscopic changes. In 77.7%, they were nodular, and in the rest of cases, they diffuse. The consistency of the lesions was compact. In most of the cases, alterations were grey in colour, rarely were dark-red or marble-like. In 91.7% of these cases, they were spread on the apical parts of large lung lobes. In 36.7% middle parts of the large lung lobes, and, in 26.7% small lung lobes, were also affected. The small lung lobes were never independently infected.

Keywords: Cysticercus pisiformis, Lepus europeus, lung lesions, Pentastomum dentatum, Protostrongylus tauricus

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Authors: Cheng-Cao Sun, Shu-Jun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, De-Jia Li

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Hsa-miRNA-326 (miR-326) has recently been discovered having anticancer efficacy in different organs. However, the role of miR-326 on non-small cell lung cancer (NSCLC) is still ambiguous. In this study, we investigated the role of miR-326 on the development of NSCLC. The results indicated that miR-326 was significantly down-regulated in primary tumor tissues and very low levels were found in NSCLC cell lines. Ectopic expression of miR-326 in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4, and up-regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-326 induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-326 inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene CCND1 was revealed to be a putative target of miR-326, which was inversely correlated with miR-326 expression in NSCLC. Taken together, our results demonstrated that miR-326 played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic CCND1.

Keywords: hsa-miRNA-326 (miR-326), cyclin D1, non-small cell lung cancer (NSCLC), proliferation, apoptosis

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Authors: Vaclav Mentl, P. Zlabek, J. Volak

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New methods of mechanical testing were developed recently that are based on making use of miniature test specimens (e.g. Small Punch Test). The most important advantage of these method is the nearly non-destructive withdrawal of test material and small size of test specimen what is interesting in cases of remaining lifetime assessment when a sufficient volume of the representative material cannot be withdrawn of the component in question. In opposite, the most important disadvantage of such methods stems from the necessity to correlate test results with the results of standardised test procedures and to build up a database of material data in service. The correlations among the miniature test specimen data and the results of standardised tests are necessary. The paper describes the results of fatigue tests performed on miniature tests specimens in comparison with traditional fatigue tests for several steels applied in power producing industry. Special miniature test specimens fixtures were designed and manufactured for the purposes of fatigue testing at the Zwick/Roell 10HPF5100 testing machine. The miniature test specimens were produced of the traditional test specimens. Seven different steels were fatigue loaded (R = 0.1) at room temperature.

Keywords: mechanical properties, miniature test specimens, correlations, small punch test, micro-tensile test, mini-charpy impact test

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Authors: Adegboyega Adeolapo Ola, Gerelene Jagganath

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One of the greatest challenges of human right in the world, especially African states is the use of child soldiers in armed conflict, constituting a major source of destruction of lives and properties. Mostly, they are in developing countries with the situation in Sub-Saharan Africa, the abduction and employment of children as soldiers is a form of exploitative labour that is tantamount to slavery. Since the end of cold war, Child soldier has increased in Africa countries like Angola, Liberia, Sierra Leone and Uganda. This study examines the main cause of the recruitment and use of child soldiers and its challenges to human right. It further assesses the role of international regional bodies and various governments in curbing child soldiers with a view to proffer suggestions on how to address some of the resultant threat of human right. The study posits that the control of small arms and light weapons is essential in curtailing the spread of child soldier and abuse of human right. This hopefully should result in the sustainability of human/child right in African continent. It is a recommendation of this study that, in order to sustain human right in the region, all Africa leaders, government and regional bodies; such as African Union, Economic Community of West African States, South African Development Community among others, should cooperate and work together to address the issue of illicit small arms, which could eventually lead to child soldier.

Keywords: arms control, child soldier, human right, small arms

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Authors: Chrislaura Carmo, Luca Deiana, Mafalda Laranjo, Abilio Sobral, Armando Cordova

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Photodynamic therapy (PDT) is currently used for the treatment of malignancies and premalignant tumors. It is based on the capture of a photosensitizing molecule (PS) which, when excited by light at a certain wavelength, reacts with oxygen and generates oxidizing species (radicals, singlet oxygen, triplet species) in target tissues, leading to cell death. BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indaceno) derivatives are emerging as important candidates for photosensitizer in photodynamic therapy of cancer cells due to their high triplet quantum yield. Today these dyes are relevant molecules in photovoltaic materials and fluorescent sensors. In this study, it will be demonstrated the possibility that BODIPY can be covalently linked to thioglycolic acid through the click reaction. Thiol−ene click chemistry has become a powerful synthesis method in materials science and surface modification. The design of biobased allyl-terminated precursors with high renewable carbon content for the construction of the thiol-ene polymer networks is essential for sustainable development and green chemistry. The work aims to synthesize the BODIPY (10-(4-(allyloxy) phenyl)-2,8-diethyl-5,5-difluoro-1,3,7,9-tetramethyl-5H-dipyrrolo[1,2-c:2',1'-f] [1,3,2] diazaborinin-4-ium-5-uide) and to click reaction with Thioglycolic acid. BODIPY was synthesized by the condensation reaction between aldehyde and pyrrole in dichloromethane, followed by in situ complexation with BF3·OEt2 in the presence of the base. Then it was functionalized with allyl bromide to achieve the double bond and thus be able to carry out the click reaction. The thiol−ene click was performed using DMPA (2,2-Dimethoxy-2-phenylacetophenone) as a photo-initiator in the presence of UV light (320–500 nm) in DMF at room temperature for 24 hours. Compounds were characterized by standard analytical techniques, including UV-Vis Spectroscopy, 1H, 13C, 19F NMR and mass spectroscopy. The results of this study will be important to link BODIPY to polymers through the thiol group offering a diversity of applications and functionalization. This new molecule can be tested as third-generation photosensitizers, in which the dye is targeted by antibodies or nanocarriers by cells, mainly in cancer cells, PDT and Photodynamic Antimicrobial Chemotherapy (PACT). According to our studies, it was possible to visualize a click reaction between allyl BODIPY and thioglycolic acid. Our team will also test the reaction with other thiol groups for comparison. Further, we will do the click reaction of BODIPY with a natural polymer linked with a thiol group. The results of the above compounds will be tested in PDT assays on various lung cancer cell lines.

Keywords: bodipy, click reaction, thioglycolic acid, allyl, thiol-ene click

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Authors: Michelle Belinda S. Weerawardana, Gobika Thiripuranathar, Priyani A. Paranagama

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Most of fresh vegetables and fruits available in the retail markets undergo a physiological disorder in its appearance and coloration, which indeed discourages consumer purchase. A loss of millions of dollars yearly to the food industry had been due to this pronounced color reaction called Enzymatic Browning which is driven due to the catalytic activity by an oxidoreductase enzyme, polyphenol oxidase (PPO). The enzyme oxidizes the phenolic compounds which are abundantly available in fruits and vegetables as substrates into quinones, which could react with proteins in its surrounding to generate black pigments, called melanins, which are highly UV-active compounds. Annona muricata (Katu anoda) and Musa acuminata (Ash plantains) is a fruit and a vegetable consumed by Sri Lankans widely due to their high nutritional values, medicinal properties and economical importance. The objective of the present study was to evaluate and determine the effective natural anti-browning inhibitors that could prevent PPO activity in the selected fruit and vegetable. Enzyme extracts from Annona muricata (Katu anoda) and Musa acuminata (Ash plantains), were prepared by homogenizing with analytical grade acetone, and pH of each enzyme extract was maintained at 7.0 using a phosphate buffer. The extracts of inhibitors were prepared using powdered ginger rhizomes and essential oil from the bark of Cinnamomum zeylanicum. Water extracts of ginger were prepared and the essential oil from Ceylon cinnamon bark was extracted using steam distillation method. Since the essential oil is not soluble in water, 0.1µl of cinnamon bark oil was mixed with 0.1µl of Triton X-100 emulsifier and 5.00 ml of water. The effect of each inhibitor on the PPO activity was investigated using catechol (0.1 mol dm-3) as the substrate and two samples of enzyme extracts prepared. The dosages of the prepared Cinnamon bark oil, and ginger (2 samples) which were used to measure the activity were 0.0035 g/ml, 0.091 g/ml and 0.087 g/ml respectively. The measurements of the inhibitory activity were obtained at a wavelength of 525 nm using the UV-visible spectrophotometer. The results evaluated thus revealed that % inhibition observed with cinnamon bark oil, and ginger for Annona muricata was 51.97%, and 60.90% respectively. The effects of cinnamon bark oil, and ginger extract on PPO activity of Musa acuminata were 49.51%, and 48.10%. The experimental findings thus revealed that Cinnamomum zeylanicum bark oil was a more effective inhibitor for PPO enzyme present in Musa acuminata and ginger was effective for PPO enzyme present in Annona muricata. Overall both the inhibitors were proven to be more effective towards the activities of PPO enzyme present in both samples. These inhibitors can thus be corroborated as effective, natural, non-toxic, anti-browning extracts, which when added to the above fruit and vegetable will increase the shelf life and also the acceptance of the product by the consumers.

Keywords: anti-browning agent, enzymatic browning, inhibitory activity, polyphenol oxidase

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Authors: Rajesh A. Rane, Shital S. Naphade, Rajshekhar Karpoormath

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Thiozolidin-4-one, a mimic of thiazolobenzimidazole (TBZ) has drawn many attentions due to its potent and selective inhibition against the HIV-1 and low toxicity by binding to the allosteric site of the reverse transcriptase (RT) as a non-nucleoside RT inhibitor (NNRTI). Similarly, marine bromopyrrole alkaloids are well known for their diverse array of anti-infective properties. Hence, we have reported synthesis and in vitro HIV-1 RT inhibitory activity of a series of 4-thiazolidinone-bromopyrrole alkaloid hybrids tethered with amide linker. The results of in vitro HIV-1 RT kit assay showed that some of the compounds, such as 4c, 4d, and 4i could effectively inhibit RT activity. Among them, compounds 4c having 4-chlorophenyl substituted 4-thiazolidione ring was the best one with the IC50 value of 0.26 µM. The sturdy emerges with key structure-activity relationship that pyrrole-NH-free core benefited inhibition against HIV-1 RT inhibition. This study identified conjugate 4c with potent activity and selectivity as promising compound for further drug development to HIV.

Keywords: antiviral drugs, bromopyrrole alkaloids, HIV-1 RT inhibition, 4-thiazolidinone

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Authors: Vivian Uchechi Okpala

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Background: Millions of workers die every year as a result of occupational hazards, accidents and injuries, which are as a result of non- compliance to the laws or legislations guiding the health, safety and welfare of workers in the industries. This and many more lead to the assessment of implementation of the health and safety contents of the Nigerian Factories Act (NFA) by small and medium scale industries in Anambra State. Objectives: The study is aimed at achieving the following specific objectives; to assess the extent of implementation of Part-II Health and Part -III Safety (General Provisions), implementation of Part II Health and Part -III Safety (General Provisions Nigerian Factories Acts based on the age of the industries, locations of the industries and level of education of the workers of the small and medium scale industries Methods: the research design that was used for this study was descriptive survey research design, Area of this study was Anambra state, The population for this study comprised 180 chairmen/presidents of union workers of manufacturing industries in Anambra State, The instrument used for this study was structured questionnaire titled ‘assessment of implementation of NFA health and safety contents by small and medium scale industries, results: From the analysis, the following findings were made: Results: The medium scale industries implemented the Part-II Health and Part III Safety (General provisions) better than the small scale industries in Anambra state, the age of the industries, location of the industries and the level of education of the workers in the industries significantly influenced the implementation of the Part III Safety (General Provisions) of NFA, the location of the industries significantly influenced the implementation of the Part II-Health (General Provisions) of NFA. Conclusion: there was generally a certain level of implementation of the factories Act, there is need for more improvement, strict inspection by the regulatory agencies. Implications of the study were highlighted and several suggestions for further studies were made. Based on the findings, several recommendations were made including that the Ministry of Labour and Productivity and the Ministry of Health should strengthen planned information, strict policies to sanction the offenders. Keywords: Occupational Health and Safety, Nigerian Factories Act

Keywords: occupational health and safety, Nigerian factories act, workers, welfare

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Authors: Davinder Singh, Jaimal Singh Khamba, Tarun Nanda

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Growth of the Indian economy has accelerated to 8% and efforts are on to further propel it to 10%. Undoubtedly, all the segments of the economy, viz. agriculture, industry and services have to improve their contribution to the economy. Growth of Micro-small and medium enterprises (MSMEs) is a sine qua non for the growth of industry, exports and other segments of the economy. Furthermore, promotion of entrepreneurship is also vital for sustenance and upward movement of the current growth trajectory of the economy. The MSME sector acts as a catalyst in upholding and encouraging the creation of the innovative spirit and entrepreneurship in the economy, thereby helping in laying the foundation for rapid industrial development. In this competitive world, they need to be able to confront the increasing competition from developed and emerging economies and to plug into the new market opportunities.

Keywords: characteristics, management, MSMEs, technology infrastructure

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Authors: P. S. Dhananjaya Swamy, B. Chinnappa, G. B. Ramesh, Naveen P. Kumar

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Kodagu district is one of the most densely forested districts in the India as around sixty five per cent of geographical areas under tree cover. Nearly 53 per cent of the flora of Kodagu is endemic. The district is also a hotspot of endemic orchids found mainly in the Thadiandamol. Shade grown, eco-friendly coffee farms are perhaps a selected few places on this planet where nature runs wild. The Kodagu accounts for more than 8.8 per cent of floral diversity of Karnataka state. Estimation of unit cost of cultivation plays a vital role in determining the governmental program their market intervention policies. On an average, planters incurred around Rs. 17041 per acre. The extent of production risk was highest among small category of planters (66 %) compared to other two exhibiting production instability. The result shows that, the coffee productivity in medium plantations was 1051.2 kg per acre as against 758.5 and 789.2 kg in the case of small and large plantations. An annual net return per acre was highest in the case of medium planters (Rs. 26109.3) as against Rs. 20566.7 and Rs. 18572.7 in the case of small and large planters. Cost of production was lowest in the case of small planters (Rs. 18.9 per kg of output) followed by medium planters (Rs. 21.2 per kg of output) and large planters (Rs. 22.5 per kg of output). The productivity of coffee is less whenever it is grown under high shade and native tree cover; it is around 6 quintals per acre when compared with low shade conditions, which is around 8.9 quintals per acre, without a significant difference in the amount invested for growing coffee. Net gain was lower by Rs. 15.5 per kg for the planters growing under high shade and native trees cover when compared with low shade and exotic trees cover.

Keywords: coffee, cultivation, economics, Kodagu

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Authors: Paramita Banerjee, K. R. S. Chandrakumar, G. P. Das

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Bulk MgH2 has drawn much attention for the purpose of hydrogen storage because of its high hydrogen storage capacity (~7.7 wt %) as well as low cost and abundant availability. However, its practical usage has been hindered because of its high hydrogen desorption enthalpy (~0.8 eV/H2 molecule), which results in an undesirable desorption temperature of 3000C at 1 bar H2 pressure. To surmount the limitations of bulk MgH2 for the purpose of hydrogen storage, a detailed first-principles density functional theory (DFT) based study on the structure and stability of neutral (Mgm) and positively charged (Mgm+) Mg nanoclusters of different sizes (m = 2, 4, 8 and 12), as well as their interaction with molecular hydrogen (H2), is reported here. It has been found that due to the absence of d-electrons within the Mg atoms, hydrogen remained in molecular form even after its interaction with neutral and charged Mg nanoclusters. Interestingly, the H2 molecules do not enter into the interstitial positions of the nanoclusters. Rather, they remain on the surface by ornamenting these nanoclusters and forming new structures with a gravimetric density higher than 15 wt %. Our observation is that the inclusion of Grimme’s DFT-D3 dispersion correction in this weakly interacting system has a significant effect on binding of the H2 molecules with these nanoclusters. The dispersion corrected interaction energy (IE) values (0.1-0.14 eV/H2 molecule) fall in the right energy window, that is ideal for hydrogen storage. These IE values are further verified by using high-level coupled-cluster calculations with non-iterative triples corrections i.e. CCSD(T), (which has been considered to be a highly accurate quantum chemical method) and thereby confirming the accuracy of our ‘dispersion correction’ incorporated DFT calculations. The significance of the polarization and dispersion energy in binding of the H2 molecules are confirmed by performing energy decomposition analysis (EDA). A total of 16, 24, 32 and 36 H2 molecules can be attached to the neutral and charged nanoclusters of size m = 2, 4, 8 and 12 respectively. Ab-initio molecular dynamics (AIMD) simulation shows that the outermost H2 molecules are desorbed at a rather low temperature viz. 150 K (-1230C) which is expected. However, complete dehydrogenation of these nanoclusters occur at around 1000C. Most importantly, the host nanoclusters remain stable up to ~500 K (2270C). All these results on the adsorption and desorption of molecular hydrogen with neutral and charged Mg nanocluster systems indicate towards the possibility of reducing the dehydrogenation temperature of bulk MgH2 by designing new Mg-based nano materials which will be able to adsorb molecular hydrogen via this weak Mg-H2 interaction, rather than the strong Mg-H bonding. Notwithstanding the fact that in practical applications, these interactions will be further complicated by the effect of substrates as well as interactions with other clusters, the present study has implications on our fundamental understanding to this problem.

Keywords: density functional theory, DFT, hydrogen storage, molecular dynamics, molecular hydrogen adsorption, nanoclusters, physisorption

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Authors: Susumu Fukita, Hiromi Kawasaki, Satoko Yamasaki, Kotomi Yamashita, Tomoko Iki

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The increase in the number of workers with mental health problems has become an issue. Many workers work in small- and medium-sized enterprises, which often support local employment and economy, especially in underpopulated mountainous areas. It is important for managers to take mental health measures for employees since there is no budget to hire health staff in small- and medium-sized enterprises. It is necessary to understand the manager's attitude toward the mental health of employees and to publicly support the manager in promoting mental health measures for employees. The purpose of this study was to study the awareness of managers of small- and medium-sized enterprises regarding the mental health of employees and to consider support for managers to take measures for the mental health of employees. Semi-structured interviews were conducted with six managers of small- and medium-sized enterprises in underpopulated mountainous areas in November 2019. Managers were asked about their awareness of the mental health of their employees. Qualitative descriptive analysis was used, and subcategories and categories were extracted. Four categories emerged. Regarding the mental health of employees, the managers acknowledged that if the appearance and behavior of the employees do not interfere with their lives, the manager judges that the employees’ mental health is normal. It was also found that the managers acknowledged that there is a comfortable working environment due to the characteristics of the underpopulated mountainous area. On the other hand, the managers acknowledged that employees are dissatisfied with salaries and management systems. In addition, it was found the manager acknowledged that some employees retire due to mental health problems. Although managers recognized that employees may be dissatisfied with salaries, they also recognized that there was a comfortable working environment due to the characteristics of the areas, with good interpersonal relationships. Economic challenges are difficult to solve in underpopulated mountainous areas. It is useful to consider measures that take advantage of the characteristics of the areas where it is easy to work because of good relations with each other, for example, to create a family-like workplace culture where managers and employees can engage in daily conversation. The managers judged that the employees were in good health if there was no interference with their lives. However, it is too late to take measures at the stage when it becomes an obstacle to life. Therefore, it is necessary to provide training for managers to learn observation techniques by which they quickly notice changes in the situation of employees and give appropriate responses; and to set up a contact point for managers to consult. Local governments should actively provide public support such as training for managers and establishing consultation desks to maintain valuable employment and local economics in underpopulated mountainous areas.

Keywords: employer, mental health, small- and medium- sized enterprises, underpopulated areas

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Authors: Opeyemi Elujulo, Aderonke Okoya, Kehinde Awokoya

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Molecularly imprinted polymers (MIP) for the adsorption of pyridine (PYD) was obtained from PYD (the template), styrene (the functional monomer), divinyl benzene (the crosslinker), benzoyl peroxide (the initiator), and water (the porogen). When the template was removed by solvent extraction, imprinted binding sites were left in the polymer material that are capable of selectively rebinding the target molecule. The material was characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. Batch adsorption experiments were performed to study the adsorption of the material in terms of adsorption kinetics, isotherms, and thermodynamic parameters. The results showed that the imprinted polymer exhibited higher affinity for PYD compared to non-imprinted polymer (NIP).

Keywords: molecularly imprinted polymer, bulk polymerization, environmental pollutant, adsorption

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Authors: Man Kyu Kim, Hansu Shin

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This study is an analysis on gravel of sand-gravel bar that stretches variously in the Duchon and Naechon stream basins, which are situated on Hong-Cheon River (a well-developed sand-gravel bar in upstream river) basins in Korea. Naechon stream mostly flows through granite zone but Duchon stream mostly flows through gneiss zone. The characteristics of gravel in the sand-gravel bar of these two branches in the upper Hongcheon River were analyzed in this study in order to understand the geomorphic development of streams depending on the differences of bedrock. Through the analysis on the roundness and flatness of gravel, we figured out an irregular trend following the increase in supply of granite gravel and gneiss gravel as we traveled downstream. The result shows that the two basins have uppermost small basin condition reflecting the mountain valley environment although it may be difficult to do an equivalent comparison to other roundness researches in Korea or in Europe. This study conducted an analysis on gravels found in small scale streams unlike the previous studies trend which mostly studies large rivers. The research provides an opportunity to offer basic data for continuous comparison research on various small basins.

Keywords: flatness, geology, roundness, sand-gravel bar

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Authors: Heiko Jessen, Laura Tanus, Slobodan Ruzicic

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Objectives: The efficacy of Stribild®, an integrase strand transfer inhibitor (INSTI) -based STR, has been evaluated in randomized clinical trials and it has demonstrated durable capability in terms of achieving sustained suppression of HIV-1 RNA-levels. However, differences in monitoring frequency, existing selection bias and profile of patients enrolled in the trials, may all result in divergent efficacy of this regimen in routine clinical settings. The aim of this study was to assess the virologic outcomes, safety and tolerability profile of Stribild® in a routine clinical setting. Methods: This was a retrospective monocentric analysis on HIV-1-infected patients, who started with or were switched to Stribild®. Virological failure (VF) was defined as confirmed HIV-RNA>50 copies/ml. The minimum time of follow-up was 24 weeks. The percentage of patients remaining free of therapeutic failure was estimated using the time-to-loss-of-virologic-response (TLOVR) algorithm, by intent-to-treat analysis. Results: We analyzed the data of 197 patients (56 ART-naïve and 141 treatment-experienced patients), who fulfilled the inclusion criteria. Majority (95.9%) of patients were male. The median time of HIV-infection at baseline was 2 months in treatment-naïve and 70 months in treatment-experienced patients. Median time [IQR] under ART in treatment-experienced patients was 37 months. Among the treatment-experienced patients 27.0% had already been treated with a regimen consisting of two NRTIs and one INSTI, whereas 18.4% of them experienced a VF. The median time [IQR] of virological suppression prior to therapy with Stribild® in the treatment-experienced patients was 10 months [0-27]. At the end of follow-up (median 33 months), 87.3% (95% CI, 83.5-91.2) of treatment-naïve and 80.3% (95% CI, 75.8-84.8) of treatment-experienced patients remained free of therapeutic failure. Considering only treatment-experienced patients with baseline VL<50 copies/ml, 83.0% (95% CI, 78.5-87.5) remained free of therapeutic failure. A total of 17 patients stopped treatment with Stribild®, 5.4% (3/56) of them were treatment-naïve and 9.9% (14/141) were treatment-experienced patients. The Stribild® therapy was discontinued in 2 (1.0%) because of VF, loss to follow-up in 4 (2.0%), and drug-drug interactions in 2 (1.0%) patients. Adverse events were in 7 (3.6%) patients the reason to switch from therapy with Stribild® and further 2 (1.0%) patients decided personally to switch. The most frequently observed adverse events were gastrointestinal side effects (20.0%), headache (8%), rash events (7%) and dizziness (6%). In two patients we observed an emergence of novel resistances in integrase-gene. The N155H evolved in one patient and resulted in VF. In another patient S119R evolved either during or shortly upon switch from therapy with Stribild®. In one further patient with VF two novel mutations in the RT-gene were observed when compared to historical genotypic test result (V106I/M and M184V), whereby it is not clear whether they evolved during or already before the switch to Stribild®. Conclusions: Effectiveness of Stribild® for treatment-naïve patients was consistent with data obtained in clinical trials. The safety and tolerability profile as well as resistance development confirmed clinical efficacy of Stribild® in a daily practice setting.

Keywords: ART, HIV, integrase inhibitor, stribild

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Authors: Hiba Mezaache

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The current study aimed to know the impact of using information and communication technology on the process of re-engineering small and medium enterprises, as the world witnessed the speed development of the latter in its field of work and the diversity of its objectives and programs, that also made its process important for the growth and development of the institution and also gaining the flexibility to face the changes that may occur in the environment of work, so in order to know the impact of information and communication technology on the success of this process, we prepared an electronic questionnaire that included (70) items, and we also used the SPSS statistical calendar to analyze the data obtained. In the end of our study, our conclusion was that there was a positive correlation between the four dimensions of information and communication technology, i.e., hardware and equipment, software, communication networks, databases, and the re-engineering process, in addition to the fact that the studied institutions attach great importance to formal communication, for its positive advantages that it achieves in reducing time and effort and costs in performing the business. We could also say that communication technology contributes to the process of formulating objectives related to the re-engineering strategy. Finally, we recommend the necessity of empowering workers to use information technology and communication more in enterprises, and to integrate them more into the activity of the enterprise by involving them in the decision-making process, and also to keep pace with the development in the field of software, hardware, and technological equipment.

Keywords: information and communication technology, re-engineering, small and medium enterprises, the impact

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Authors: Harche Rima, Laoufi Nadia Aicha

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The present work consists of studying the behavior of steel, copper, and aluminum vis-à-vis the corrosion in an aqueous medium in the presence of the antifreeze COOLELF MDX -26°C. For this, we have studied the influence of the temperature and the different concentrations of the antifreeze on the corrosion of these three metals, this will last for two months by the polarization method and weight loss. In the end, we investigated the samples with the optic microscope to know their surface state. The aim of this work is the protection of contraptions. The use of antifreeze in ordinary water has a high efficiency against steel corrosion, as demonstrated by electrochemical tests (potential monitoring as a function of time and tracing polarization curves). The inhibition rate is greater than 99% for different volume concentrations, ranging from 40% to 60%. The speeds are in turn low in the order of 10-4 mm/year. On the other hand, the addition of antifreeze to ordinary water increases the corrosion potential of steel by more than 400 mV.

Keywords: corrosion and prevention, steel, copper, aluminum, corrosion inhibitor, anti-cooling

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Authors: Nuhi Arslani, Aleks Brumec

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Adhesive small bowel obstruction (ASBO) accounts for 20% of emergency surgical procedures and intraabdominal adhesions account for 65% of such cases. In a 10-year post-operative period of abdominal surgery patients, around 35% of them will be readmitted because of ASBO. The first step in approaching ASBOs is using the Bologna guidelines, which include a thorough initial evaluation to diagnose or rule out an ASBO and then proceed with either further imaging studies or emergency surgery, which can be either open or laparoscopic. The contraindications for a laparoscopic approach include hemodynamic instability of the patient and infections in the peritoneum or port sites. Studies have shown that a laparoscopic approach to adhesiolysis is linked with a significantly smaller risk of readmissions and reoperations as well as with faster recovery time and fewer postoperative infections, but has a higher risk of bowel injuries, so a careful selection of patients is required. Although studies favor a laparoscopic approach, many countries still prefer a laparotomy, often because a laparoscopic approach requires surgeons to be highly skilled in the procedure. In the US and UK, between 50 and 60% of surgeons would approach an ASBO with laparoscopy, while in Italy, this number is around 15% and it is most likely similar in Slovenia. We believe that in the right cases and in the right patients, a laparoscopic approach can be equally feasible for treating ASBOs and is associated with fewer intraoperative and postoperative complications.

Keywords: adhesive small bowel obstruction, laparoscopy, adhesions, adhesiolysis

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Authors: Mansa Radhakrishnan, Anwar Ali, Muhammad Rizwan Mughal

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Many universities around the world are working on modular and low budget architecture of small spacecraft to reduce the development cost of the overall system. This paper focuses on the design of a modular solar power harvesting system for a hexagonal-shaped small satellite. The designed solar power harvesting systems are composed of solar panels and power converter subsystems. The solar panel is composed of solar cells mounted on the external face of the printed circuit board (PCB), while the electronic components of power conversion are mounted on the interior side of the same PCB. The solar panel with dimensions 16.5cm × 99cm is composed of 36 solar cells (each solar cell is 4cm × 7cm) divided into four parallel banks where each bank consists of 9 solar cells. The output voltage of a single solar cell is 2.14V, and the combined output voltage of 9 series connected solar cells is around 19.3V. The output voltage of the solar panel is boosted to the satellite power distribution bus voltage level (28V) by a boost converter working on a constant voltage maximum power point tracking (MPPT) technique. The solar panel module is an eight-layer PCB having embedded coil in 4 internal layers. This coil is used to control the attitude of the spacecraft, which consumes power to generate a magnetic field and rotate the spacecraft. As power converter and distribution subsystem components are mounted on the PCB internal layer, therefore it is mandatory to do thermal analysis in order to ensure that the overall module temperature is within thermal safety limits. The main focus of the overall design is on compactness, miniaturization, and efficiency enhancement.

Keywords: small satellites, power subsystem, efficiency, MPPT

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Authors: Meghdad Payan, Kostas Senetakis, Arman Khoshghalb, Nasser Khalili

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Dynamic properties of soils, especially at the range of very small strains, are of particular interest in geotechnical engineering practice for characterization of the behavior of geo-structures subjected to a variety of stress states. This study reports on the small-strain dynamic properties of sand-silt mixtures with particular emphasis on the effect of non-plastic fines content on the small strain shear modulus (Gmax), Young’s Modulus (Emax), material damping (Ds,min) and Poisson’s Ratio (v). Several clean sands with a wide range of grain size characteristics and particle shape are mixed with variable percentages of a silica non-plastic silt as fines content. Prepared specimens of sand-silt mixtures at different initial void ratios are subjected to sequential torsional and flexural resonant column tests with elastic dynamic properties measured along an isotropic stress path up to 800 kPa. It is shown that while at low percentages of fines content, there is a significant difference between the dynamic properties of the various samples due to the different characteristics of the sand portion of the mixtures, this variance diminishes as the fines content increases and the soil behavior becomes mainly silt-dominant, rendering no significant influence of sand properties on the elastic dynamic parameters. Indeed, beyond a specific portion of fines content, around 20% to 30% typically denoted as threshold fines content, silt is controlling the behavior of the mixture. Using the experimental results, new expressions for the prediction of small-strain dynamic properties of sand-silt mixtures are developed accounting for the percentage of silt and the characteristics of the sand portion. These expressions are general in nature and are capable of evaluating the elastic dynamic properties of sand-silt mixtures with any types of parent sand in the whole range of silt percentage. The inefficiency of skeleton void ratio concept in the estimation of small-strain stiffness of sand-silt mixtures is also illustrated.

Keywords: damping ratio, Poisson’s ratio, resonant column, sand-silt mixture, shear modulus, Young’s modulus

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Authors: Mirna Febriani

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The use of stainless steel wires in the field of dentistry is widely used, especially for orthodontic and prosthodontic treatment using stainless steel wire. The oral cavity is the ideal environment for corrosion, which can be caused by saliva. Prevention of corrosion on stainless steel wires can be done by using an organic or non-organic corrosion inhibitor. One of the organic inhibitors that can be used to prevent corrosion is the leaves of breadfruit. The method used for this research using Atomic Absorption Spectrophotometric test. The results showed that the difference of chromium ion releases on soaking in saliva and breadfruit leaf extracts on days 1, 3, 7 and 14. Statically calculation with independent T-test with p < 0,05 showed the significant difference. The conclusion of this study shows that breadfruit leaf extract can inhibit the corrosion rate of stainless steel wires.

Keywords: chromium ion, stainless steel, artificial saliva, breadfruit leaf

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Authors: Sundaram Arulmozhiraja, Kanade Shimizu, Yuta Yamamoto, Satoshi Ichikawa, Maenaka Katsumi, Hiroaki Tokiwa

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Drug discovery is shifting from small molecule based drugs targeting local active site to middle molecules (MM) targeting large, flat, and groove-shaped binding sites, for example, protein-protein interface because at least half of all targets assumed to be involved in human disease have been classified as “difficult to drug” with traditional small molecules. Hence, MMs such as peptides, natural products, glycans, nucleic acids with various high potent bioactivities become important targets for drug discovery programs in the recent years as they could be used for ‘undruggable” intracellular targets. Cell membrane permeability is one of the key properties of pharmacodynamically active MM drug compounds and so evaluating this property for the potential MMs is crucial. Computational prediction for cell membrane permeability of molecules is very challenging; however, recent advancement in the molecular dynamics simulations help to solve this issue partially. It is expected that MMs with high membrane permeability will enable drug discovery research to expand its borders towards intracellular targets. Further to understand the chemistry behind the permeability of MMs, it is necessary to investigate their conformational changes during the permeation through membrane and for that their interactions with the membrane field should be studied reliably because these interactions involve various non-bonding interactions such as hydrogen bonding, -stacking, charge-transfer, polarization dispersion, and non-classical weak hydrogen bonding. Therefore, parameters-based classical mechanics calculations are hardly sufficient to investigate these interactions rather, quantum mechanical (QM) calculations are essential. Fragment molecular orbital (FMO) method could be used for such purpose as it performs ab initio QM calculations by dividing the system into fragments. The present work is aimed to study the cell permeability of middle molecules using molecular dynamics simulations and FMO-QM calculations. For this purpose, a natural compound syringolin and its analogues were considered in this study. Molecular simulations were performed using NAMD and Gromacs programs with CHARMM force field. FMO calculations were performed using the PAICS program at the correlated Resolution-of-Identity second-order Moller Plesset (RI-MP2) level with the cc-pVDZ basis set. The simulations clearly show that while syringolin could not permeate the membrane, its selected analogues go through the medium in nano second scale. These correlates well with the existing experimental evidences that these syringolin analogues are membrane-permeable compounds. Further analyses indicate that intramolecular -stacking interactions in the syringolin analogues influenced their permeability positively. These intramolecular interactions reduce the polarity of these analogues so that they could permeate the lipophilic cell membrane. Conclusively, the cell membrane permeability of various middle molecules with potent bioactivities is efficiently studied using molecular dynamics simulations. Insight of this behavior is thoroughly investigated using FMO-QM calculations. Results obtained in the present study indicate that non-bonding intramolecular interactions such as hydrogen-bonding and -stacking along with the conformational flexibility of MMs are essential for amicable membrane permeation. These results are interesting and are nice example for this theoretical calculation approach that could be used to study the permeability of other middle molecules. This work was supported by Japan Agency for Medical Research and Development (AMED) under Grant Number 18ae0101047.

Keywords: fragment molecular orbital theory, membrane permeability, middle molecules, molecular dynamics simulation

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Authors: Cornellia Ayu, Putrianti Herni, Saptoto Robertus

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In the context of global tourism and creative economies, digital maturity has become a crucial factor for the sustainable development of small and medium enterprises (SMEs). This paper explores the journey toward digital maturity among SMEs in Sleman, Yogyakarta, Indonesia, focusing on their empowerment to foster sustainable tourism and creative economy growth. The study adopts a mixed-methods approach, integrating qualitative interviews with SME owners and quantitative surveys to assess their digital capabilities and readiness. Data were collected from a diverse sample of SMEs engaged in various sectors, including crafts and culinary services. Findings reveal significant gaps in digital literacy and infrastructure, impeding the full realization of digital benefits. However, targeted interventions, such as digital training programs and the provision of affordable technology, have shown promise in bridging these gaps. The study concludes that enhancing digital maturity among SMEs is vital for their competitiveness and sustainability in the modern economy. The insights gained can inform policymakers and stakeholders aiming to bolster the digital transformation of SMEs in similar contexts.

Keywords: digital maturity, small medium enterprises, digital literacy, sustainable tourism, creative economy

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Authors: B. Roopa Sri, Y Lakshmi Naidu

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Chemical Graph Theory (CGT) is the branch of mathematical chemistry in which molecules are modeled to study their physicochemical properties using molecular descriptors. Amongst these descriptors, topological indices play a vital role in predicting the properties by defining the graph topology of the molecule. Recently, the bond-additive topological index known as the Mostar index has been proposed. In this paper, we compute the Mostar-type indices of octane isomers and use the data obtained to perform QSPR analysis. Furthermore, we show the correlation between the Mostar type indices and the properties.

Keywords: chemical graph theory, mostar type indices, octane isomers, qspr analysis, topological index

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Authors: Delphine Morales, Florian Lombart, Agathe Truchot, Pauline Maire, Pascale Vigneron, Antoine Galmiche, Catherine Lok, Muriel Vayssade

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Targeted therapy molecules are used as a first-line treatment for metastatic melanoma with B-Raf mutation. Nevertheless, these molecules can cause side effects to patients and are efficient on 50 to 60 % of them. Indeed, melanoma cell sensitivity to targeted therapy molecules is dependent on tumor microenvironment (cell-cell and cell-extracellular matrix interactions). To better unravel factors modulating cell sensitivity to B-Raf inhibitor, we have developed and compared several melanoma models: from metastatic melanoma cells cultured as monolayer (2D) to a co-culture in a 3D dermal equivalent. Cell response was studied in different melanoma cell lines such as SK-MEL-28 (mutant B-Raf (V600E), sensitive to Vemurafenib), SK-MEL-3 (mutant B-Raf (V600E), resistant to Vemurafenib) and a primary culture of dermal human fibroblasts (HDFn). Assays have initially been performed in a monolayer cell culture (2D), then a second time on a 3D dermal equivalent (dermal human fibroblasts embedded in a collagen gel). All cell lines were treated with Vemurafenib (a B-Raf inhibitor) for 48 hours at various concentrations. Cell sensitivity to treatment was assessed under various aspects: Cell proliferation (cell counting, EdU incorporation, MTS assay), MAPK signaling pathway analysis (Western-Blotting), Apoptosis (TUNEL), Cytokine release (IL-6, IL-1α, HGF, TGF-β, TNF-α) upon Vemurafenib treatment (ELISA) and histology for 3D models. In 2D configuration, the inhibitory effect of Vemurafenib on cell proliferation was confirmed on SK-MEL-28 cells (IC50=0.5 µM), and not on the SK-MEL-3 cell line. No apoptotic signal was detected in SK-MEL-28-treated cells, suggesting a cytostatic effect of the Vemurafenib rather than a cytotoxic one. The inhibition of SK-MEL-28 cell proliferation upon treatment was correlated with a strong expression decrease of phosphorylated proteins involved in the MAPK pathway (ERK, MEK, and AKT/PKB). Vemurafenib (from 5 µM to 10 µM) also slowed down HDFn proliferation, whatever cell culture configuration (monolayer or 3D dermal equivalent). SK-MEL-28 cells cultured in the dermal equivalent were still sensitive to high Vemurafenib concentrations. To better characterize all cell population impacts (melanoma cells, dermal fibroblasts) on Vemurafenib efficacy, cytokine release is being studied in 2D and 3D models. We have successfully developed and validated a relevant 3D model, mimicking cutaneous metastatic melanoma and tumor microenvironment. This 3D melanoma model will become more complex by adding a third cell population, keratinocytes, allowing us to characterize the epidermis influence on the melanoma cell sensitivity to Vemurafenib. In the long run, the establishment of more relevant 3D melanoma models with patients’ cells might be useful for personalized therapy development. The authors would like to thank the Picardie region and the European Regional Development Fund (ERDF) 2014/2020 for the funding of this work and Oise committee of "La ligue contre le cancer".

Keywords: 3D human skin model, melanoma, tissue engineering, vemurafenib efficiency

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