Search results for: small molecule inhibitor

Authors: Erich Gomes Schaitza, Antônio Francisco Savi, Glaucia Aparecida Prates

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The penetration of renewable energy into the electricity supply in Brazil is high, one of the highest in the World. Centralized hydroelectric generation is the main source of energy, followed by biomass and wind. Surprisingly, mini and micro-generation are negligible, with less than 2,000 connections to the national grid. In 2015, a new regulatory framework was put in place to change this situation. In the agricultural sector, the framework was complemented by the offer of low interest rate loans to in-farm renewable generation. Brazil proposed to more than double its area of planted forests as part of its INDC- Intended Nationally Determined Contributions to the UNFCCC-U.N. Framework Convention on Climate Change (UNFCCC). This is an ambitious target which will be achieved only if forests are attractive to farmers. Therefore, this paper analyses whether planting forests for in-farm energy generation with a with a woodchip gasifier is economically viable for microgeneration under the new framework and at if they could be an economic driver for forest plantation. At first, a static case was analyzed with data from Eucalyptus plantations in five farms. Then, a broader analysis developed with the use of Monte Carlo technique. Planting short rotation forests to generate energy could be a viable alternative and the low interest loans contribute to that. There are some barriers to such systems such as the inexistence of a mature market for small scale equipment and of a reference network of good practices and examples.

Keywords: biomass, distribuited generation, small-scale, Monte Carlo

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Authors: Lubica Muckova, Petr Jost, Jaroslav Pejchal, Daniel Jun

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The development of acetylcholinesterase reactivators, i.e. antidotes against organophosphorus poisoning, is an important goal of defence research. The aim of this study was to compare cytotoxicity and chemical structure of 5 currently available (pralidoxime, trimedoxime, obidoxime, methoxime, and asoxime) and 4 newly developed compounds (K027, K074, K075, and K203). In oximes, there could be at least four important structural factors affecting their toxicity, including the number of oxime groups in the molecule, the position of oxime group(s) on pyridinium ring, the length of carbon linker, and the substitution by oxygen or insertion of the double bond into the connection chain. The cytotoxicity of tested substances was measured using colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay (MTT assay) in SH-SY5Y cell line. Toxicity was expressed as toxicological index IC₅₀. The tested compounds showed different cytotoxicity ranging from 1.5 to 27 mM. K027 was the least, and methoxime was the most toxic reactivator. The lowest toxicity was found in a monopyridinium reactivator and bispyridinium reactivators with simple 3C carbon linker. Shortening of connection chain length to 1C, incorporation of oxygen moiety into 3C compounds, elongation of carbon linker to 4C and insertion of a double bond into 4C substances increase AChE reactivators' cytotoxicity. Acknowledgements: This work was supported by a long-term organization development plan Medical Aspects of Weapons of Mass Destruction of the Faculty of Military Health Sciences, University of Defence.

Keywords: acetylcholinesterase, cytotoxicity, organophosphorus poisoning, reactivators of acetylcholinesterase

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Authors: Gajanan M. Sonwane

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Nowadays, the entire pharmaceutical industry is facing the challenge of increasing efficiency and innovation. The major hurdles are the growing cost of research and development and a concurrent stagnating number of new chemical entities (NCEs). Hence, the challenge is to select the most druggable targets and to search the equivalent drug-like compounds, which also possess specific pharmacokinetic and toxicological properties that allow them to be developed as drugs. The present research work includes the studies of developing new anticancer heterocycles by using molecular modeling techniques. The heterocycles synthesized through such methodology are much effective as various physicochemical parameters have been already studied and the structure has been optimized for its best fit in the receptor. Hence, on the basis of the literature survey and considering the need to develop newer anticancer agents, new phenazinamine derivatives were designed by subjecting the nucleus to molecular modeling, viz., GQSAR analysis and docking studies. Simultaneously, these designed derivatives were subjected to in silico prediction of biological activity through PASS studies and then in silico toxicity risk assessment studies. In PASS studies, it was found that all the derivatives exhibited a good spectrum of biological activities confirming its anticancer potential. The toxicity risk assessment studies revealed that all the derivatives obey Lipinski’s rule. Amongst these series, compounds 4c, 5b and 6c were found to possess logP and drug-likeness values comparable with the standard Imatinib (used for anticancer activity studies) and also with the standard drug methotrexate (used for antimitotic activity studies). One of the most notable mutations is the threonine to isoleucine mutation at codon 315 (T315I), which is known to be resistant to all currently available TKI. Enzyme assay planned for confirmation of target selective activity.

Keywords: drug design, tyrosine kinases, anticancer, Phenazinamine

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Authors: Hideo Sawada

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Fluoroalkyl end-capped oligomers [RF-(M)n-RF; RF = fluoroalkyl groups; M = radical polymerizable monomers] can form nanometre size-controlled self-assembled oligomeric aggregates through the aggregations of end-capped fluoroalkyl groups. Fluoroalkyl end-capped oligomeric aggregates can also interact with guest molecules to afford fluorinated aggregate/guest molecule nanocomposites; although the corresponding non-fluorinated oligomers cannot form such molecular aggregates to interact with guest molecules. For example, silica nanoparticles should act as guest molecules in fluorinated oligomeric aggregate cores to give new fluorinated oligomer-coated silica nanoparticles (fluorinated oligomer/silica nanocomposites). In these fluoroalkyl end-capped oligomers/silica nanocomposites, some fluorinated oligomers/silica nanocomposites were found to exhibit no weight loss behavior corresponding to the contents of oligomers in the silica matrices even after calcination at 800 oC. Fluoroalkyl end-capped vinyltrimethoxysilane oligomer-coated silica nanoparticles can be prepared by the sol-gel reaction of the corresponding fluorinated oligomer under alkaline conditions. The modified glass surface treated with this fluorinated oligomeric nanoparticle exhibited a completely super-hydrophobic characteristic. These fluorinated nanoparticles were also applied to the surface modification possessing a super-oleophobic characteristic. Not only fluoroalkyl end-capped oligomers but also low molecular weight fluorinated surfactants such as perfluoro-1,3-propanedisulfonic acid (PFPS) were applied to the preparation of fluorinated surfactants/silica nanocomposites to give no weight loss in proportion to the content of the surfactants in the nanocomposites even after calcination at 800 oC.

Keywords: fluorinated oligomer, silica nanocomposite, nonflammable characteristic, superamphiphobic chracteristic

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Authors: Yehjune Heo

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Fingerprint Anti-Spoofing approaches have been actively developed and applied in real-world applications. One of the main problems for Fingerprint Anti-Spoofing is not robust to unseen samples, especially in real-world scenarios. A possible solution will be to generate artificial, but realistic fingerprint samples and use them for training in order to achieve good generalization. This paper contains experimental and comparative results with currently popular GAN based methods and uses realistic synthesis of fingerprints in training in order to increase the performance. Among various GAN models, the most popular StyleGAN is used for the experiments. The CNN models were first trained with the dataset that did not contain generated fake images and the accuracy along with the mean average error rate were recorded. Then, the fake generated images (fake images of live fingerprints and fake images of spoof fingerprints) were each combined with the original images (real images of live fingerprints and real images of spoof fingerprints), and various CNN models were trained. The best performances for each CNN model, trained with the dataset of generated fake images and each time the accuracy and the mean average error rate, were recorded. We observe that current GAN based approaches need significant improvements for the Anti-Spoofing performance, although the overall quality of the synthesized fingerprints seems to be reasonable. We include the analysis of this performance degradation, especially with a small number of samples. In addition, we suggest several approaches towards improved generalization with a small number of samples, by focusing on what GAN based approaches should learn and should not learn.

Keywords: anti-spoofing, CNN, fingerprint recognition, GAN

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Authors: Bethany Leake, Samantha Caton, Paul Norman, Jill Edmondson

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With the majority of the UK population residing in urban areas and with the pressures both environmentally and socially on rural agriculture, the role of urban food production, particularly urban horticulture (UH), is increasingly important in the future of UK food security. UH has the potential to provide an important contribution to urban diets and to provide additional benefits to human health and well-being. While allotments are the traditional focus of UH and play an important role, as access to this type of land is limited and unequal across cities, other forms of UH space, such as domestic growing, will need to be utilized to provide a significant contribution to urban diets. It is theorized that this smaller scale of growing may also be a more accessible way of engaging novice growers in UH. A collaborative research project, Urban Harvest, was designed between the University of Sheffield and Sheffield-based food organizations, which aimed to engage inexperienced gardeners in UH by providing them with home food-growing kits (Grow-Kits). Grow-Kits were provided to 189 participants across Sheffield in 2022, 48% of whom had never grown food before. Data collected through surveys and interviews will help us to evaluate the effect of small-scale food growing on health and wellbeing and the potential of this type of scheme to encourage future UH engagement. This data and increasing evidence on the co-benefits of UH have important implications not only for local food security but also for urban health inequalities and the potential use of this activity for preventative healthcare.

Keywords: urban horticulture, health and wellbeing, food security, nutrition

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Authors: Rita Ghosh, Joykrishna Dey

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PEG-based amphiphiles are of tremendous importance for its widespread applications in pharmaceutics, household purposes, and drug delivery. Previously, a number of single PEG-tailed amphiphiles having significant applications have been reported from our group. Therefore, it was of immense interest to explore the properties and application potential of PEG-based double tailed amphiphiles. Herein, for the first time, two novel double PEG-tailed amphiphiles having different PEG chain lengths have been developed. The self-assembly behavior of the newly developed amphiphiles in aqueous buffer (pH 7.0) was thoroughly investigated at 25 oC by a number of techniques including, 1H-NMR, and steady-state and time-dependent fluorescence spectroscopy, dynamic light scattering, transmission electron microscopy, atomic force microscopy, and isothermal titration calorimetry. Despite having two polar PEG chains both molecules were found to have strong tendency to self-assemble in aqueous buffered solution above a very low concentration. Surprisingly, the amphiphiles were shown to form stable vesicles spontaneously at room temperature without any external stimuli. The results of calorimetric measurements showed that the vesicle formation is driven by the hydrophobic effect (positive entropy change) of the system, which is associated with the helix-to-random coil transition of the PEG chain. The spectroscopic data confirmed that the bilayer membrane of the vesicles is constituted by the PEG chains of the amphiphilic molecule. Interestingly, the vesicles were also found to exhibit structural transitions upon addition of salts in solution. These properties of the vesicles enable them as potential candidate for drug delivery.

Keywords: double-tailed amphiphiles, fluorescence, microscopy, PEG, vesicles

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Authors: Evgeny E. Tereshatov, C. M. Folden

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Ionic liquids and deep eutectic mixtures represent so-called non-conventional solvents. The former, composed of discrete ions, is a salt with a melting temperature below 100°С. The latter, consisting of hydrogen bond donors and acceptors, is a mixture of at least two compounds, resulting in a melting temperature depression in comparison with that of the individual moiety. These systems also can be water-immiscible, which makes them applicable for metal extraction. This work will cover interactions of In, Tl, Ir, and Rh in hydrochloric acid media with eutectic mixtures and Er, Ir, and At in a gas phase with chemically modified α-detectors. The purpose is to study chemical systems based on non-conventional solvents in terms of their interaction with metals. Once promising systems are found, the next step is to modify the surface of α-detectors used in the online element production at cyclotrons to get the detector chemical selectivity. Initially, the metal interactions are studied by means of the liquid-liquid extraction technique. Then appropriate molecules are chemisorbed on the surrogate surface first to understand the coating quality. Finally, a detector is covered with the same molecule, and the metal sorption on such detectors is studied in the online regime. It was found that chemical treatment of the surface can result in 99% coverage with a monolayer formation. This surface is chemically active and can adsorb metals from hydrochloric acid solutions. Similarly, a detector surface was modified and tested during cyclotron-based experiments. Thus, a procedure of detectors functionalization has been developed, and this opens an interesting opportunity of studying chemisorption of elements which do not have stable isotopes.

Keywords: mechanism, radioisotopes, solvent extraction, gas phase sorption

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Authors: Tej Varma Y, Debi D. Pant

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Photophysics and rotational dynamics of the fluorescent probe, 6-methoxyquinoline (6MQ) with cationic surfactant, alkyltrimethylammonium bromide (nTAB) micelle solutions have been investigated (n = 12, 14 and 16). Absorption and emission peaks of the dye have been observed to shift at concentrations around critical micellar concentration (cmc) of nTAB compared to that of bulk solutions suggesting probe is in a lower polar environment. The probe senses changes in polarity (ET (30)) brought about by variation of surfactant chain length concentration and is invariably solubilized in the aqueous interface or palisade layer. The order of change in polarity observed was DTAB > CTAB > TTAB. The binding constant study shows that the probe binds strongest with TTAB (is of the order TTAB > CTAB > DTAB) due to deeper penetration into the micelle. The anisotropy decay for the probe in all the nTAB micelles studied have been rationalized based on a two-step model consisting of fast-restricted rotation of the probe and slow lateral diffusion of the probe in the micelle that is coupled to the overall rotation of the micelle. Fluorescence lifetime measurements of probe in the cationic micelles demonstrate the close proximity of the 6MQ to the Br - counterions. The fluorescence lifetimes of TTAB and DTAB are much shorter than in CTAB. These results indicate that 6MQ resides to a substantial degree in the head group region of the micelles. All the changes observed in the steady state fluorescence, microenvironment, fluorescence lifetimes, fluorescence anisotropy, and other calculations are in agreement with each other suggesting binding of the cationic surfactant with the neutral dye molecule.

Keywords: photophysics, chain length, ntaB, micelles

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Authors: Gavin Quibell, Martin Kleynhans, Margot Soler

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The Sendai Framework notes that disaster risk reduction is essential for sustainable development, and Disaster Risk Reduction is included in 3 of the Sustainable Development Goals (SDGs), and 4 of the SDG targets. However, apart from promoting better governance and resourcing of disaster management agencies, little guidance is given how low-income nations can balance investments across the SDGs to achieve sustainable development in an increasingly climate vulnerable world with increasing prevalence of flood and drought disasters. As one of the world’s poorest nations, Malawi must balance investments across all the SDGs. This paper explores how Malawi’s National Guidelines for Community-based Flood Risk Management integrate sustainable development and flood management objectives at different administrative levels. While Malawi periodically suffers from large, widespread flooding, the greatest impacts are felt through the smaller annual floods and flash floods. The Guidelines address this through principles that recognize that while the protection of human life is the most important priority for flood risk management, addressing the impacts of floods on the rural poor and the economy requires different approaches. The National Guidelines are therefore underpinned by the following; 1. In the short-term investments in flood risk management must focus on breaking the poverty – vulnerability cycle; 2. In the long-term investments in the other SDGs will have the greatest flood risk management benefits; 3. If measures are in place to prevent loss of life and protect strategic infrastructure, it is better to protect more people against small and medium size floods than fewer people against larger floods; 4. Flood prevention measures should focus on small (1:5 return period) floods; 5. Flood protection measures should focus on small and medium floods (1:20 return period) while minimizing the risk of failure in larger floods; 6. The impacts of larger floods ( > 1:50) must be addressed through improved preparedness; 7. The impacts of climate change on flood frequencies are best addressed by focusing on growth not overdesign; and 8. Manage floods and droughts conjunctively. The National Guidelines weave these principles into Malawi’s approach to flood risk management through recommendations for planning and implementing flood prevention, protection and preparedness measures at district, traditional authority and village levels.

Keywords: flood risk management in low-income countries, sustainable development, investments in prevention, protection and preparedness, community-based flood risk management, Malawi

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Authors: Mohamed Abdelwahed

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We propose an optimization algorithm for the geometric control of fluid flow. The used approach is based on the topological sensitivity analysis method. It consists in studying the variation of a cost function with respect to the insertion of a small obstacle in the domain. Some theoretical and numerical results are presented in 2D and 3D.

Keywords: sensitivity analysis, topological gradient, shape optimization, stokes equations

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Authors: E. Al-Essa, R. Bello-Mendoza, D. G. Wareham

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Anaerobic batch experiments were conducted to investigate the effect of magnetite-supplementation (7 mM) on methane production from digested sludge undergoing two different microbial growth phases, namely fresh sludge (exponential growth phase) and degassed sludge (endogenous decay phase). Three different particle sizes were assessed: small (50 - 150 nm), medium (168 – 490 nm) and large (800 nm - 4.5 µm) particles. Results show that, in the case of the fresh sludge, magnetite significantly enhanced the methane production rate (up to 32%) and reduced the lag phase (by 15% - 41%) as compared to the control, regardless of the particle size used. However, the cumulative methane produced at the end of the incubation was comparable in all treatment and control bottles. In the case of the degassed sludge, only the medium-sized magnetite particles increased significantly the methane production rate (12% higher) as compared to the control. Small and large particles had little effect on the methane production rate but did result in an extended lag phase which led to significantly lower cumulative methane production at the end of the incubation period. These results suggest that magnetite produces a clear and positive effect on methane production only when an active and balanced microbial community is present in the anaerobic digester. It is concluded that, (i) the effect of magnetite particle size on increasing the methane production rate and reducing lag phase duration is strongly influenced by the initial metabolic state of the microbial consortium, and (ii) the particle size would positively affect the methane production if it is provided within the nanometer size range.

Keywords: anaerobic digestion, iron oxide, methanogenesis, nanoparticle

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Authors: Numfon Rakkhumkaew, Takeru Kawasaki, Makoto Fujie, Takashi Yamada

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Chlorella viruses or chloroviruses contain a gene that encodes a function for chitin synthesis, which is expressed early in viral infection to produce chitin polysaccharide, a polymer of β-1, 4-linked GlcNAc, on the outside of Chlorella cell wall. Interestingly, chlorovirus system is an eco-friendly system which converses CO2 and solar energy from the environment into useful materials. However, infected Chlorella cells are lysed at the final stage of viral infection, and this phenomenon is caused the breaking down of polysaccharide. To postpone the lysing period and prolong the synthesis of chitin polysaccharide on cells, the slow growing virus incorporated with aphidicolin treatment, an inhibitor of DNA synthesis, was investigated. In this study, a total of 25 virus isolates from water samples in Japan region were analyzed for CHS (the gene for CH synthase) gene by PCR (polymerase chain reaction). The accumulation and appearance of chitin polysaccharide on infected cells were detected by biotinylated chitin-binding proteins WGA (wheat germ agglutinin)-biotin for chitin in conjunction with avidin-Cy 2 or Cy 3 and investigated by fluorescence microscopy, observed as green or yellow fluorescence over the cell surface. Among all chlorovirus isolates, cells infected with CNF1 revealed the accumulation of chitin over the cell surface within 30 min p.i. and continued to accumulate on cells until 4 h p.i. before cell lyses which was 1.6 times longer accumulation period than cells infected with CVK2 (prototype virus). Furthermore, addition of aphidicolin could extend the chitin accumulation on cells infected with CNF1 until 8 h p.i. before cell lyses. Whereas, CVK2-infected cells treated with aphidicolin could prolong the chitin synthesis only for 6 h p.i. before cell lyses. Therefore, chitin synthesis by Chlorella-virus system could be prolonged by using slow-growing viral isolates and with aphidicolin.

Keywords: chitin, chlorovirus, Chlorella virus, aphidicolin

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Authors: Hamid Reza Khodaei, Behnaz Mahdavi, Alireza Banitaba

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Nitric oxide (NO) plays an important role in all sexual activities of animals. It is made in body from NO syntheses enzyme and L-arginin molecule. NO can make band with sulfur-iron complexes and due to production of steroid sexual hormones related to enzymes which have this complex, NO can change the activity of these enzymes. NO affects many cells including endothelial cells of veins, macrophages and mast cells. These cells are found in testis leydig cells and therefore are important source of NO in testis tissue. Minimizing damages to sperm at the time of sperm freezing and thawing is really important. The goal of this study was to determine the function of NO before freezing and its effects on quality and viability of sperms after thawing and incubation. 4 Holstein bulls were selected from the age of 4, and artificial insemination was done for 3 weeks (2 times a week). Treatments were 0, 10, 50 and 100 nm of sodium nitroprusside (SNP). Data analysis was performed by SAS98 program. Also, mean comparison was done using Duncan's multiple ranges test (P<0.05). Concentrations used were found to increase motility and viability of spermatozoa at 1, 2 and 3 hours after thawing significantly (P<0.05) but there was no significant difference at zero time. SNP levels reduced the amount of lipid peroxidation in sperm membrane, increased acrosome health and improved samples membranes especially in 50 and 100 nm treatments. According to results, adding SNP to semen diluents increases motility and viability of spermatozoa. Also, it reduces lipid peroxidation in sperm membrane and improves sperm function.

Keywords: sperm motility, nitric oxide, lipid peroxidation, spermatozoa

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Authors: H. T. Le Luong, C. Hénaux, F. Messine, G. Bueno-Mariani, S. Mollov, N. Voyer

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This paper presents a comparative study of different modular brushless wound rotor synchronous machine (MB-WRSM). The goal of the study is to highlight the structure which offers the best fault tolerant capability and the highest output performances. The fundamental winding factor is calculated by using the method based on EMF phasors as a significant criterion to select the preferred number of phases, stator slots, and poles. With the limited number of poles for a small machine (3.67kW/7000rpm), 15 different machines for preferred phase/slot/pole combinations are analyzed using two-dimensional (2-D) finite element method and compared according to three criteria: torque density, torque ripple and efficiency. The 7phase/7slot/6pole machine is chosen with the best compromise of high torque density, small torque ripple (3.89%) and high nominal efficiency (95%). This machine is then compared with a reference design surface permanent magnet synchronous machine (SPMSM). In conclusion, this paper provides an electromagnetic analysis of a new brushless wound-rotor synchronous machine using multiphase non-overlapping fractional slot double layer winding. The simulation results are discussed and demonstrate that the MB-WRSM presents interesting performance features, with overall performance closely matching that of an equivalent SPMSM.

Keywords: finite element method (FEM), machine performance, modular wound rotor synchronous machine, non-overlapping concentrated winding

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Authors: Mewa Singh

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Nanomedicine, a fusion of nanotechnology and medicine, is an emerging technology ideally suited to the targeted therapies. Nanoparticles overcome the low selectivity of anti-cancer drugs toward the tumor as compared to normal tissue and hence result-in less severe side-effects. Our new technology, HYBRID-NANOENGINEERING™, uses a new molecule (MR007) in the creation of nanoparticles that not only helps in nanonizing the medicine but also provides synergy to the medicine. The simplified manufacturing process will result in reduced manufacturing costs. Treatment is made more convenient because hybrid nanomedicines can be produced in oral, injectable or transdermal formulations. The manufacturing process uses no protein, oil or detergents. The particle size is below 180 nm with a narrow distribution of size. Importantly, these properties confer great stability of the structure. The formulation does not aggregate in plasma and is stable over a wide range of pH. The final hybrid formulation is stable for at least 18 months as a powder. More than 97 drugs, including paclitaxel, docetaxel, tamoxifen, doxorubicinm prednisone, and artemisinin have been nanonized in water soluble formulations. Preclinical studies on cell cultures of tumors show promising results. Our HYBRID-NANOENGINEERING™ platform enables the design and development of hybrid nano-pharmaceuticals that combine efficacy with tolerability, giving patients hope for both extended overall survival and improved quality of life. This study would discuss or present this new discovery of HYBRID-NANOENGINEERING™ which targets drug delivery, synergistic, and potentiating effects, and barriers of drug delivery and advanced drug delivery systems.

Keywords: nano-medicine, nano-particles, drug delivery system, pharmaceuticals

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Authors: Francesco Pantano, Marta Fogolari, Michele Iuliani, Sonia Simonetti, Silvia Cavaliere, Marco Russano, Fabrizio Citarella, Bruno Vincenzi, Silvia Angeletti, Giuseppe Tonini

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Background: Although immune checkpoint inhibitors (ICIs) have changed the treatment paradigm of non–small cell lung cancer (NSCLC), these drugs fail to elicit durable responses in the majority of NSCLC patients. The gut microbiota, able to regulate immune responsiveness, is emerging as a promising, modifiable target to improve ICIs response rates. Since the oral microbiome has been demonstrated to be the primary source of bacterial microbiota in the lungs, we investigated its composition as a potential predictive biomarker to identify and select patients who could benefit from immunotherapy. Methods: Thirty-five patients with stage IV squamous and non-squamous cell NSCLC eligible for an anti-PD-1/PD-L1 as monotherapy were enrolled. Saliva samples were collected from patients prior to the start of treatment, bacterial DNA was extracted using the QIAamp® DNA Microbiome Kit (QIAGEN) and the 16S rRNA gene was sequenced on a MiSeq sequencing instrument (Illumina). Results: NSCLC patients were dichotomized as “Responders” (partial or complete response) and “Non-Responders” (progressive disease), after 12 weeks of treatment, based on RECIST criteria. A prevalence of the phylum Candidatus Saccharibacteria was found in the 10 responders compared to non-responders (abundance 5% vs 1% respectively; p-value = 1.46 x 10-7; False Discovery Rate (FDR) = 1.02 x 10-6). Moreover, a higher prevalence of Saccharibacteria Genera Incertae Sedis genus (belonging to the Candidatus Saccharibacteria phylum) was observed in "responders" (p-value = 6.01 x 10-7 and FDR = 2.46 x 10-5). Finally, the patients who benefit from immunotherapy showed a significant abundance of TM7 Phylum Sp Oral Clone FR058 strain, member of Saccharibacteria Genera Incertae Sedis genus (p-value = 6.13 x 10-7 and FDR=7.66 x 10-5). Conclusions: These preliminary results showed a significant association between oral microbiota and ICIs response in NSCLC patients. In particular, the higher prevalence of Candidatus Saccharibacteria phylum and TM7 Phylum Sp Oral Clone FR058 strain in responders suggests their potential immunomodulatory role. The study is still ongoing and updated data will be presented at the congress.

Keywords: oral microbiota, immune checkpoint inhibitors, non-small cell lung cancer, predictive biomarker

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Authors: Edokpa Idemudia Waziri, Salisu S. Umar

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The Hotellng’s T^2 is a well-known statistic for detecting a shift in the mean vector of a multivariate normal distribution. Control charts based on T have been widely used in statistical process control for monitoring a multivariate process. Although it is a powerful tool, the T statistic is deficient when the shift to be detected in the mean vector of a multivariate process is small and consistent. The Multivariate Exponentially Weighted Moving Average (MEWMA) control chart is one of the control statistics used to overcome the drawback of the Hotellng’s T statistic. In this paper, the probability distribution of the Average Run Length (ARL) of the MEWMA control chart when the quality characteristics exhibit substantial cross correlation and when the process is in-control and out-of-control was derived using the Markov Chain algorithm. The derivation of the probability functions and the moments of the run length distribution were also obtained and they were consistent with some existing results for the in-control and out-of-control situation. By simulation process, the procedure identified a class of ARL for the MEWMA control when the process is in-control and out-of-control. From our study, it was observed that the MEWMA scheme is quite adequate for detecting a small shift and a good way to improve the quality of goods and services in a multivariate situation. It was also observed that as the in-control average run length ARL0¬ or the number of variables (p) increases, the optimum value of the ARL0pt increases asymptotically and as the magnitude of the shift σ increases, the optimal ARLopt decreases. Finally, we use the example from the literature to illustrate our method and demonstrate its efficiency.

Keywords: average run length, markov chain, multivariate exponentially weighted moving average, optimal smoothing parameter

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Authors: Supannika Klangphukhiew, Roongnapa Srichana, Rina Patramanon

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Cortisol has been used as a well-known commercial stress biomarker. A homeostasis response to psychological stress is indicated by an increased level of cortisol produced in hypothalamus-pituitary-adrenal (HPA) axis. Chronic psychological stress contributing to the high level of cortisol relates to several health problems. In this study, the cortisol biosensor was fabricated that mimicked the natural receptors. The artificial antibodies were prepared using molecular imprinted polymer technique that can imitate the performance of natural anti-cortisol antibody with high stability. Cortisol-molecular imprinted polymer (cortisol-MIP) was obtained using the multi-step swelling and polymerization protocol with cortisol as a target molecule combining methacrylic acid:acrylamide (2:1) with bisacryloyl-1,2-dihydroxy-1,2-ethylenediamine and ethylenedioxy-N-methylamphetamine as cross-linkers. Cortisol-MIP was integrated to the sensor. It was coated on the disposable screen-printed carbon electrode (SPCE) for portable electrochemical analysis. The physical properties of Cortisol-MIP were characterized by means of electron microscope techniques. The binding characteristics were evaluated via covalent patterns changing in FTIR spectra which were related to voltammetry response. The performance of cortisol-MIP modified SPCE was investigated in terms of detection range, high selectivity with a detection limit of 1.28 ng/ml. The disposable cortisol biosensor represented an application of MIP technique to recognize steroids according to their structures with feasibility and cost-effectiveness that can be developed to use in point-of-care.

Keywords: stress biomarker, cortisol, molecular imprinted polymer, screen-printed carbon electrode

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Authors: Hussain Mustatab Wahedi, Sun You Kim

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Skin acts as a barrier against the harmful environmental factors. Integrity and timely recovery of the skin from injuries and harmful effects of radiations is thus very important. This study aimed to investigate the importance of Sirt1 in the recovery of skin from UVB-induced damage and cutaneous wounds by using natural and synthetic novel Sirt1 activators. Juglone, known as a natural Pin1 inhibitor, and NED416 a novel synthetic Sirt1 activator were checked for their ability to regulate the expression and activity of Sirt1 and hence photo-damage and wound healing in cultured skin cells (NHDF and HaCaT cells) and mouse model by using Sirt1 siRNA knockdown, cell migration assay, GST-Pulldown assay, western blot analysis, tube formation assay, and immunohistochemistry. Interestingly, Sirt1 knockdown inhibited skin cell migration in vitro. Juglone up regulated the expression of Sirt1 in both the cell lines under normal and UVB irradiated conditions, enhanced Sirt1 activity and increased the cell viability by reducing reactive oxygen species synthesis and apoptosis. Juglone promoted wound healing by increasing cell migration and angiogenesis through Cdc42/Rac1/PAK, MAPKs and Smad pathways in skin cells. NED416 upregulated Sirt1 expression in HaCaT and NHDF cells as well as increased Sirt1 activity. NED416 promoted the process of wound healing in early as well as later stages by increasing macrophage recruitment, skin cell migration, and angiogenesis through Cdc42/Rac1 and MAPKs pathways. So, both these compounds activated Sirt1 and promoted the process of wound healing thus pointing towards the possible role of Sirt1 in skin regeneration and wound healing.

Keywords: skin regeneration, wound healing, Sirt1, UVB light

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Authors: Jeni A. Popescu, Sorin G. Tomescu, Valeriu A. Vilag

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The paper focuses on the potential methods of increasing the performance of a microturbine by combining additional elements available for utilization in a cogeneration plant. The activity is carried out within the framework of a project aiming to develop, manufacture and test a microturbine functional model with high potential in energetic industry utilization. The main goal of the analysis is to determine the parameters of the fluid flow passing through each section of the turbine, based on limited data available in literature for the focus output power range or provided by experimental studies, starting from a reference cycle, and considering different cycle options, including simple, intercooled and recuperated options, in order to optimize a small cogeneration plant operation. The studied configurations operate under the same initial thermodynamic conditions and are based on a series of assumptions, in terms of individual performance of the components, pressure/velocity losses, compression ratios, and efficiencies. The thermodynamic analysis evaluates the expected performance of the microturbine cycle, while providing a series of input data and limitations to be included in the development of the experimental plan. To simplify the calculations and to allow a clear estimation of the effect of heat transfer between fluids, the working fluid for all the thermodynamic evolutions is, initially, air, the combustion being modelled by simple heat addition to the system. The theoretical results, along with preliminary experimental results are presented, aiming for a correlation in terms of microturbine performance.

Keywords: cogeneration, microturbine, performance, thermodynamic analysis

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Authors: Ankit Nagar, Dinesh Kumar Nauriyal, Sukhpal Singh

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This paper examines the key determinants of farmers’ access to agricultural extension services, sources of agricultural extension services preferred and accessed by the farmers. An ordered logistic regression model was used to analyse the data of the 360 sample households based on a primary survey conducted in western Uttar Pradesh, India. The study finds that farmers' decision to engage in the agricultural extension programme is significantly influenced by factors such as education level, gender, farming experience, social group, group membership, farm size, credit access, awareness about the extension scheme, farmers' perception, and distance from extension sources. The most intriguing finding of this study is that the progressive farmers, which have long been regarded as a major source of knowledge diffusion, are the most distrusted sources of information as they are suspected of withholding vital information from potential beneficiaries. The positive relationship between farm size and ‘Access’ underlines that the extension services should revisit their strategies for targeting more marginal and small farmers constituting over 85 percent of the agricultural households by incorporating their priorities in their outreach programs. The study suggests that marginal and small farmers' productive potential could still be greatly augmented by the appropriate technology, advisory services, guidance, and improved market access. Also, the perception of poor quality of the public extension services can be corrected by initiatives aimed at building up extension workers' capacity.

Keywords: agriculture, access, extension services, ordered logistic regression

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Authors: Amir Zeb, Shailima Rampogu, Minky Son, Ayoung Baek, Sang H. Yoon, Keun W. Lee

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Neurotoxic insults activate calpain, which in turn produces truncated p25 from p35. p25 forms hyperactivated Cdk5/p25 complex, and thereby induces severe neuropathological aberrations including hyperphosphorylated tau, neuroinflammation, apoptosis, and neuronal death. Inhibition of Cdk5/p25 complex alleviates aberrant phosphorylation of tau to mitigate AD pathology. PHA-793887 and Roscovitine have been investigated as selective inhibitors of Cdk5/p25 with IC50 values 5nM and 160nM, respectively, but their mechanistic studies remain unknown. Herein, computational simulations have explored the binding mode and interaction mechanism of PHA-793887 and Roscovitine with Cdk5/p25. Docking results suggested that PHA-793887 and Rsocovitine have occupied the ATP-binding site of Cdk5 and obtained highest docking (GOLD) score of 66.54 and 84.03, respectively. Furthermore, molecular dynamics (MD) simulation demonstrated that PHA-793887 and Roscovitine established stable RMSD of 1.09 Å and 1.48 Å with Cdk5/p25, respectively. Profiling of polar interactions suggested that each inhibitor formed hydrogen bonds (H-bond) with catalytic residues of Cdk5 and could remain stable throughout the molecular dynamics simulation. Additionally, binding free energy calculation by molecular mechanics/Poisson–Boltzmann surface area (MM/PBSA) suggested that PHA-793887 and Roscovitine had lowest binding free energies of -150.05 kJ/mol and -113.14 kJ/mol, respectively with Cdk5/p25. Free energy decomposition demonstrated that polar energy by H-bond between the Glu81 of Cdk5 and PHA-793887 is the essential factor to make PHA-793887 highly selective towards Cdk5/p25. Overall, this study provided substantial evidences to explore mechanistic interactions of the selective inhibitors of Cdk5/p25 and could be used as fundamental considerations in the development of structure-based selective inhibitors of Cdk5/p25.

Keywords: Cdk5/p25 inhibition, molecular modeling of Cdk5/p25, PHA-793887 and roscovitine, selective inhibition of Cdk5/p25

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Authors: Reza Karimpour

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Ports play a decisive role in the EU's external and internal trade, as about 74% of imports and exports and 37% of exchanges go through ports. Although ports, especially Deep Sea Shipping (DSS) ports, are integral nodes within multimodal logistic flows, Short Sea Shipping (SSS) and inland waterways are not so well integrated. The automated vessels and supply chain optimisations for sustainable shortsea shipping (MOSES) project aims to enhance the short sea shipping component of the European supply chain by addressing the vulnerabilities and strains related to the operation of large containerships. The MOSES concept can be shortly described as a large containership (mother-vessel) approaching a DSS port (or a large container terminal). Upon her arrival, a combined intelligent mega-system consisting of the MOSES Autonomous tugboat swarm for manoeuvring and the MOSES adapted AutoMoor system. Then, container handling processes are ready to start moving containers to their destination via hinterland connections (trucks and/or rail) or to be shipped to destinations near small ports (on the mainland or island). For the first case, containers are stored in a dedicated port area (Storage area), waiting to be moved via trucks and/or rail. For the second case, containers are stacked by existing port equipment near-dedicated berths of the DSS port. They then are loaded on the MOSES Innovative Feeder Vessel, equipped with the MOSES Robotic Container-Handling System that provides (semi-) autonomous (un) feeding of the feeder. The Robotic Container-Handling System is remotely monitored through a Shore Control Centre. When the MOSES innovative Feeder vessel approaches the small port, where her docking is achieved without tugboats, she automatically unloads the containers using the Robotic Container-Handling System on the quay or directly on trucks. As a result, ports with minimal or no available infrastructure may be effectively integrated with the container supply chain. Then, the MOSES innovative feeder vessel continues her voyage to the next small port, or she returns to the DSS port. MOSES exploitation activity mainly aims to exploit research outcomes beyond the project, facilitate utilisation of the pilot results by others, and continue the pilot service after the project ends. By the mid-lifetime of the project, the exploitation plan introduces the reader to the MOSES project and its key exploitable results. It provides a plan for delivering the MOSES innovations to the market as part of the overall exploitation plan.

Keywords: automated vessels, exploitation, shortsea shipping, supply chain

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Authors: Armaghan Eslami, Nasrin Arshadi

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Scarce resources are the inseparable part of organization life. This fact that only small number of the employees can have these resources such as promotion, raise, and recognition can cause competition among employees, which create competitive climate. As well as any other competition, small number wins the reward, and a great number loses, one of the possible emotional reactions to this loss is negative emotions like malicious envy. In this case, the envious person may try to harm the envied person by reducing the prosocial behavior. Prosocial behavior is a behavior that aimed to benefit others. The main propose of this action is to maintain and increase well-being and well-fare of others. Therefore, one of the easiest ways for harming envied one is to suppress prosocial behavior. Prosocial behavior has positive and important implication for organizational efficiency. Our results supported our model and suggested that competitive climate has a significant effect on increasing workplace envy and on the other hand envy has significant negative impact on prosocial behavior. Our result also indicated that envy is the mediator in the relation between competitive climate and prosocial behavior. Organizational competitive climate can cause employees respond envy with negative emotion and hostile and damaging behavior toward envied person. Competition can lead employees to look out for proof of their self-worthiness; and, furthermore, they measure their self-worth, value and respect by the superiority that they gain in competitions. As a result, loss in competitions can harm employee’s self-definition and they try to protect themselves by devaluating envied other and being ‘less friendly’ to them. Some employees may find it inappropriate to engage in the harming behavior, but they may believe there is nothing against withholding the prosocial behavior.

Keywords: competitive climate, mediator, prosocial behavior, workplace envy

Procedia PDF Downloads 362

Authors: Janine Just, Kerstin Meints

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The research aims to compare vocabulary size and grammatical development between US American English- and British English-speaking children at age 2;0. As there is evidence that precocious children with large vocabularies develop grammar skills earlier than their typically developing peers, it was investigated if this also holds true across varieties of English. Thus, if US American children start to produce words earlier than their British counterparts, this could mean that US children are also at an advantage in the early developmental stages of acquiring grammar. This research employs a British English adaptation of the MacArthur-Bates CDI Words and Sentences (Lincoln Toddler CDI) to compare vocabulary and also grammar scores with the updated US Toddler CDI norms. At first, the Lincoln TCDI was assessed for its concurrent validity with the Preschool Language Scale (PLS-5 UK). This showed high correlations for the vocabulary and grammar subscales between the tests. In addition, the frequency of the Toddler CDI’s words was also compared using American and British English corpora of adult spoken and written language. A paired-samples t-test found a significant difference in word frequency between the British and the American CDI demonstrating that the TCDI’s words were indeed of higher frequency in British English. We then compared language and grammar scores between US (N = 135) and British children (N = 96). A two-way between groups ANOVA examined if the two samples differed in terms of SES (i.e. maternal education) by investigating the impact of SES and country on vocabulary and sentence complexity. The two samples did not differ in terms of maternal education as the interaction effects between SES and country were not significant. In most cases, scores were not significantly different between US and British children, for example, for overall word production and most grammatical subscales (i.e. use of words, over- regularizations, complex sentences, word combinations). However, in-depth analysis showed that US children were significantly better than British children at using some noun categories (i.e. people, objects, places) and several categories marking early grammatical development (i.e. pronouns, prepositions, quantifiers, helping words). However, the effect sizes were small. Significant differences for grammar were found for irregular word forms and progressive tense suffixes. US children were more advanced in their use of these grammatical categories, but the effect sizes were small. In sum, while differences exist in terms of vocabulary and grammar ability, favouring US children, effect sizes were small. It can be concluded that most British children are ‘catching up’ with their US American peers at age 2;0. Implications of this research will be discussed.

Keywords: first language acquisition, grammar, parent report instrument, vocabulary

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Authors: S. Chaudhuri, P. A. Bhobe

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Fe₂TiSn is a non-magnetic full Heusler alloy with a small gap (~ 0.07 eV) at the Fermi level. The electronic structure is highly symmetric in both the spin bands and a small percentage of substitution of holes or electrons can push the system towards spin polarization. A stable 100% spin polarization or half-metallicity is very desirable in the field of spintronics, making Fe₂TiSn a highly attractive material. However, this composition suffers from an inherent anti-site disorder between Fe and Ti sites. This paper reports on the method adopted to control the anti-site disorder and the realization of the half-metallic ground state in Fe₂TiSn, achieved by chemical substitution. Here, Sb was substituted at Sn site to obtain Fe₂TiSn₁₋ₓSbₓ compositions with x = 0, 0.1, 0.25, 0.5 and 0.6. All prepared compositions with x ≤ 0.6 exhibit long-range L2₁ ordering and a decrease in Fe – Ti anti-site disorder. The transport and magnetic properties of Fe₂TiSn₁₋ₓSbₓ compositions were investigated as a function of temperature in the range, 5 K to 400 K. Electrical resistivity, magnetization, and Hall voltage measurements were carried out. All the experimental results indicate the presence of the half-metallic ground state in x ≥ 0.25 compositions. However, the value of saturation magnetization is small, indicating the presence of compensated magnetic moments. The observed magnetic moments' values are in close agreement with the Slater–Pauling rule in half-metallic systems. Magnetic interactions in Fe₂TiSn₁₋ₓSbₓ are understood from the local crystal structural perspective using extended X-ray absorption fine structure (EXAFS) spectroscopy. The changes in bond distances extracted from EXAFS analysis can be correlated with the hybridization between constituent atoms and hence the RKKY type magnetic interactions that govern the magnetic ground state of these alloys. To complement the experimental findings, first principle electronic structure calculations were also undertaken. The spin-polarized DOS complies with the experimental results for Fe₂TiSn₁₋ₓSbₓ. Substitution of Sb (an electron excess element) at Sn–site shifts the majority spin band to the lower energy side of Fermi level, thus making the system 100% spin polarized and inducing long-range magnetic order in an otherwise non-magnetic Fe₂TiSn. The present study concludes that a stable half-metallic system can be realized in Fe₂TiSn with ≥ 50% Sb – substitution at Sn – site.

Keywords: antisite disorder, EXAFS, Full Heusler alloy, half metallic ferrimagnetism, RKKY interactions

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Authors: Yeun Sug Jeong, Yeongseon Jang, Rhim Ryoo, Donha Choi, Sung-Suk Lee, Kang-Hyeon Ka

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Broussonetia kazinoki (paper mulberry) is a plant native to Asia, and it grows at the foot of a mountain. Its bark is used as a raw material of Hanji, traditional Korean paper, and fruit is used as a medicinal material. However, inside the bark (woody part) is not used and discarded. We tried to use it for Lentinula edodes (oak mushroom) cultivation. It is commonly cultivated using oak trees and sawdust, but it could be grown with other trees. The woody part of paper mulberry was ground and mixed with oak sawdust by five different ratios. The 1.2 kg cylindrical bag media were prepared and water contents were adjusted to 65%. The media were autoclaved at 100℃ for 60 min and 121℃ for 90 min. Two strains of oak mushroom, NIFoS 2462 and NIFoS 2778 were inoculated and cultivated for 90 days in dark condition, and 40 days in light condition. Compared to the control, the mycelial growth period was long and the hardness of the media was low when paper mulberry sawdust was added. After incubation period, fruiting was stimulated at 18℃ and more than 85% humidity. After each flush, there was a resting period of 2 weeks. In the first flush, mushrooms were small, and a lot of small mushrooms were harvested. On the other hand, no mushrooms of 5 g or less were harvested in the secondary flush. The highest productivity was obtained in a 3:1 ratio of paper mulberry and oak sawdust. The size of NIFoS 2778 was uniform in each condition. On the other hand, NIFoS 2462 had smaller mushrooms in the media containing paper mulberry sawdust, but the appearance was not significantly different. This study showed that paper mulberry wood could be used to grow oak mushrooms and some oak sawdust could be substituted.

Keywords: Broussonetia kazinoki, cultivation, Lentinula edodes, oak mushroom

Procedia PDF Downloads 219

Authors: Outokesh Fatemeh, Jourabchi Keivan, Talebi Maryam, Nikbakht Fatemeh

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Mayamei is a small town in Iran that is located between Shahrud and Sabzevar cities, on the Silk Road. It enjoys a history of approximately 1000 years. An alley entitled ‘Aghayan’ exists in this town that comprises residential buildings of a famous family. Bathhouse, mosque, telegraph center, cistern are all related to this alley. This architectural complex belongs to Sadat Mousavi, who is one of the Mayamei's major grandees and religious household. The alley after construction has been inherited from generation to generation within the family masters. The purpose of this study, which was conducted on Aghayan alley and its associated complex, was to elucidate Iranian vernacular domestic architecture of Qajar era in small towns and villages. We searched for large, medium, and small architectural patterns in the contemplated complex, and tried to elaborate their evolution from past to the present. The other objective of this project was finding a correlation between changes in the lifestyle of the alley’s inhabitants with the form of the building's architecture. Our investigation methods included: literature review especially in regard to historical travelogues, peer site visiting, mapping, interviewing of the elderly people of the Mousavi family (the owners), and examining the available documents especially the 4 meters’ scroll-type testament of 150 years ago. For the analysis of the aforementioned data, an effort was made to discover (1) the patterns of placing of different buildings in respect of the others, (2) finding the relation between function of the buildings with their relative location in the complex, as was considered in the original design, and (3) possible changes of functions of the buildings during the time. In such an investigation, special attention was paid to the chronological changes of lifestyles of the residents. In addition, we tried to take all different activities of the residents into account including their daily life activities, religious ceremonies, etc. By combining such methods, we were able to obtain a picture of the buildings in their original (construction) state, along with a knowledge of the temporal evolution of the architecture. An interesting finding is that the Aghayan complex seems to be a big structure of the horizontal type apartments, which are placed next to each other. The houses made in this way are connected to the adjacent neighbors both by the bifacial rooms and from the roofs.

Keywords: Iran, Qajar period, vernacular domestic architecture, life style, residential complex

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Authors: Mohamed Ahmed M. Azab

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The shortage of fresh water is a major problem in several areas of the world such as arid regions and coastal zones in several countries of Arabian Gulf. Fortunately, arid regions are exposed to high levels of solar irradiation most the year, which makes the utilization of solar energy a promising solution to such problem with zero harmful emission (Green System). The main objective of this work is to conduct a feasibility study of utilizing small autonomous water desalination units powered by photovoltaic modules as a green renewable energy resource to be employed in different isolated zones as a source of drinking water for some scattered societies where the installation of huge desalination stations are discarded owing to the unavailability of electric grid. Yanbu City is chosen as a case study where the Renewable Energy Center exists and equipped with all sensors to assess the availability of solar energy all over the year. The study included two types of available water: the first type is brackish well water and the second type is seawater of coastal regions. In the case of well water, two versions of desalination units are involved in the study: the first version is based on day operation only. While the second version takes into consideration night operation also, which requires energy storage system as batteries to provide the necessary electric power at night. According to the feasibility study results, it is found that utilization of small autonomous desalinations unit is applicable and economically accepted in the case of brackish well water. While in the case of seawater the capital costs are extremely high and the cost of desalinated water will not be economically feasible unless governmental subsidies are provided. In addition, the study indicated that, for the same water production, the utilization of energy storage version (day-night) adds additional capital cost for batteries, and extra running cost for their replacement, which makes the unit price not only incompetent with day-only unit but also with conventional units powered by diesel generator (fossil fuel) owing to the low prices of fuel in the kingdom. However, the cost analysis shows that the price of the produced water per cubic meter of day-night unit is similar to that produced from the day-only unit provided that the day-night unit operates theoretically for a longer period of 50%.

Keywords: solar energy, water desalination, reverse osmosis, arid regions

Procedia PDF Downloads 454