Search results for: selective permeability

Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

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The recent advancements in synthetic chemistry and nanotechnology fostered the development of different nanocarriers for enhanced intracellular delivery of pharmaceutical agents to tumor cells. Polymeric micelles (PMs), characterized by small size, appreciable drug loading capacity (DLC), better accumulation in tumor tissue via enhanced permeability and retention (EPR) effect, and the ability to avoid detection and subsequent clearance by the mononuclear phagocyte (MNP) system, are convenient to improve the poor solubility, slow absorption and non-selective biodistribution of payloads embedded in their hydrophobic cores and hence, enhance the therapeutic efficacy of chemotherapeutic agents. Recently, redox-responsive polymeric micelles have gained significant attention for the delivery and controlled release of anticancer drugs in tumor cells. In this study, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA, and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. The successful synthesis of the copolymers was verified by different spectroscopic techniques. Above the critical micelle concentration, the amphiphilic copolymer, Bi(mPEG-PLGA)-Se₂, self-assembled into stable micelles. The DLS data indicated that the hydrodynamic diameter of the micelles (123.9 ± 0.85 nm) was suitable for extravasation into the tumor cells through the EPR effect. The drug loading content (DLC) and encapsulation efficiency (EE) of DOX-loaded micelles were found to be 6.61 wt% and 54.9%, respectively. The DOX-loaded micelles showed initial burst release accompanied by sustained release trend where 73.94% and 69.54% of encapsulated DOX was released upon treatment with 6mM GSH and 0.1% H₂O₂, respectively. The biocompatible nature of Bi(mPEG-PLGA)-Se₂ copolymer was confirmed by the cell viability study. In addition, the DOX-loaded micelles exhibited significant inhibition against HeLa cells (44.46%), at a maximum dose of 7.5 µg/mL. The fluorescent microscope images of HeLa cells treated with 3 µg/mL (equivalent DOX concentration) revealed efficient internalization and accumulation of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles in the cytosol of cancer cells. In conclusion, the intelligent, biocompatible, and the redox stimuli-responsive behavior of Bi(mPEG-PLGA)-Se₂ copolymer marked the potential applications of diselenide-linked mPEG-PLGA micelles for the delivery and on-demand release of chemotherapeutic agents in cancer cells.

Keywords: anticancer drug delivery, diselenide bond, polymeric micelles, redox-responsive

Procedia PDF Downloads 89

Authors: Yuanxia Zheng, Min Zhong, Cong Xin, Guoxiong Liu, Liqi Zhu

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Trust is a critical foundation of social interaction and development, playing a significant role in the physical and mental well-being of children, as well as their social participation. Previous research has demonstrated that young children do not blindly trust others but make selective trust judgments based on available information. The characteristics of speakers can influence children’s trust judgments. According to Mayer et al.’s model of trust, these characteristics of speakers, including ability, benevolence, and integrity, can influence children’s trust judgments. While previous research has focused primarily on the effects of ability and benevolence, there has been relatively little attention paid to integrity, which refers to individuals’ adherence to promises, fairness, and justice. This study focuses specifically on how keeping/breaking promises affects young children’s trust judgments. The paradigm of selective trust was employed in two experiments. A sample size of 100 children was required for an effect size of w = 0.30，α = 0.05，1-β = 0.85, using G*Power 3.1. This study employed a 2×2 within-subjects design to investigate the effects of moral valence of promises (within-subjects factor: moral vs. immoral promises), and fulfilment of promises (within-subjects factor: kept vs. broken promises) on children’s trust judgments (divided into declarative and promising contexts). In Experiment 1 adapted binary choice paradigms, presenting 118 preschoolers (62 girls, Mean age = 4.99 years, SD = 0.78) with four conflict scenarios involving the keeping or breaking moral/immoral promises, in order to investigate children’s trust judgments. Experiment 2 utilized single choice paradigms, in which 112 preschoolers (57 girls, Mean age = 4.94 years, SD = 0.80) were presented four stories to examine their level of trust. The results of Experiment 1 showed that preschoolers selectively trusted both promisors who kept moral promises and those who broke immoral promises, as well as their assertions and new promises. Additionally, the 5.5-6.5-year-old children are more likely to trust both promisors who keep moral promises and those who break immoral promises more than the 3.5- 4.5-year-old children. Moreover, preschoolers are more likely to make accurate trust judgments towards promisor who kept moral promise compared to those who broke immoral promises. The results of Experiment 2 showed significant differences of preschoolers’ trust degree: kept moral promise > broke immoral promise > broke moral promise ≈ kept immoral promise. This study is the first to investigate the development of trust judgement in moral promise among preschoolers aged 3.5-6.5. The results show that preschoolers can consider both valence and fulfilment of promises when making trust judgments. Furthermore, as preschoolers mature, they become more inclined to trust promisors who keep moral promises and those who break immoral promises. Additionally, the study reveals that preschoolers have the highest level of trust in promisors who kept moral promises, followed by those who broke immoral promises. Promisors who broke moral promises and those who kept immoral promises are trusted the least. These findings contribute valuable insights to our understanding of moral promises and trust judgment.

Keywords: promise, trust, moral judgement, preschoolers

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Authors: Nompumelelo P. Mathebula, Roger A. Sheldon, Daniel P. Pienaar, Moira L. Bode

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The preparation of enantiopure Morita-Baylis-Hillman (MBH) adducts remains a challenge in organic chemistry. MBH adducts are highly functionalised compounds which act as key intermediates in the preparation of compounds of medicinal importance. MBH adducts are prepared in racemic form by reacting various aldehydes and activated alkenes in the presence of DABCO. Enantiopure MBH adducts can be obtained by employing Enzymatic kinetic resolution (EKR). This technique has been successfully demonstrated in our group, amongst others, using lipases in either hydrolysis or transesterification reactions. As these methods only allow 50% of each enantiomer to be obtained, our interest grew in exploring other enzymatic methods for the synthesis of enantiopure MBH adducts where, theoretically, 100% of the desired enantiomer could be obtained.Dehydrogenase enzymes can be employed on prochiral substrates to obtain optically pure compounds by reducing carbon-carbon double bonds or carbonyl groups of ketones. Ketoreductases have been used historically to obtain enantiopure secondary alcohols on an industrial scale. Ketoreductases are NAD(P)H-dependent enzymes and thus require nicotinamide as a cofactor. This project focuses on employing ketoreductase enzymes to selectively reduce ketones derived from Morita-Baylis-Hillman (MBH) adducts in order to obtain these adducts in enantiopure form.Results obtained from this study will be reported. Good enantioselectivity was observed using a range of different ketoreductases, however, reactions were complicated by the formation of an unexpected by-product, which was characterised employing single crystal x-ray crystallography techniques. Methods to minimise by-product formation are currently being investigated.

Keywords: ketoreductase, morita-baylis-hillman, selective reduction, x-ray crystallography

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Authors: Michael Huber, Maximilian J. Poller, Jens Tochtermann, Wolfgang Korth, Andreas Jess, Jakob Albert

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Aside from the desulfurisation, the denitrogenation of fuels is of great importance to minimize the environmental impact of transport emissions. The oxidative reaction pathway of organic nitrogen in the catalytic oxidative denitrogenation could be successfully elucidated. This is the first time such a pathway could be traced in detail in non-microbial systems. It was found that the organic nitrogen is first oxidized to nitrate, which is subsequently reduced to molecular nitrogen via nitrous oxide. Hereby, the organic substrate serves as a reducing agent. The discovery of this pathway is an important milestone for the further development of fuel denitrogenation technologies. The United Nations aims to counteract global warming with Net Zero Emissions (NZE) commitments; however, it is not yet foreseeable when crude oil-based fuels will become obsolete. In 2021, more than 50 million barrels per day (mb/d) were consumed for the transport sector alone. Above all, heteroatoms such as sulfur or nitrogen produce SO₂ and NOx during combustion in the engines, which is not only harmful to the climate but also to health. Therefore, in refineries, these heteroatoms are removed by hy-drotreating to produce clean fuels. However, this catalytic reaction is inhibited by the basic, nitrogenous reactants (e.g., quinoline) as well as by NH3. The ion pair of the nitrogen atom forms strong pi-bonds to the active sites of the hydrotreating catalyst, which dimin-ishes its activity. To maximize the desulfurization and denitrogenation effectiveness in comparison to just extraction and adsorption, selective oxidation is typically combined with either extraction or selective adsorption. The selective oxidation produces more polar compounds that can be removed from the non-polar oil in a separate step. The extraction step can also be carried out in parallel to the oxidation reaction, as a result of in situ separation of the oxidation products (ECODS; extractive catalytic oxidative desulfurization). In this process, H8PV5Mo7O40 (HPA-5) is employed as a homogeneous polyoxometalate (POM) catalyst in an aqueous phase, whereas the sulfur containing fuel components are oxidized after diffusion from the organic fuel phase into the aqueous catalyst phase, to form highly polar products such as H₂SO₄ and carboxylic acids, which are thereby extracted from the organic fuel phase and accumulate in the aqueous phase. In contrast to the inhibiting properties of the basic nitrogen compounds in hydrotreating, the oxidative desulfurization improves with simultaneous denitrification in this system (ECODN; extractive catalytic oxidative denitrogenation). The reaction pathway of ECODS has already been well studied. In contrast, the oxidation of nitrogen compounds in ECODN is not yet well understood and requires more detailed investigations.

Keywords: oxidative reaction pathway, denitrogenation of fuels, molecular catalysis, polyoxometalate

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Authors: Malay K. Das, Bhanu P. Sahu

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Furosemide is a weakly acidic diuretic indicated for treatment of edema and hypertension. It has very poor solubility but high permeability through stomach and upper gastrointestinal tract (GIT). Due to its limited solubility it has poor and variable oral bioavailability of 10-90%. The aim of this study was to enhance the oral bioavailability of furosemide by preparation of nanosuspensions. The nanosuspensions were prepared by nanoprecipitation with sonication using DMSO (dimethyl sulfoxide) as a solvent and water as an antisolvent (NA). The prepared nanosuspensions were sterically stabilized with polyvinyl acetate (PVA).These were characterized for particle size, ζ potential, polydispersity index, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) pattern and release behavior. The effect of nanoprecipitation on oral bioavailability of furosemide nanosuspension was studied by in vitro dissolution and in vivo absorption study in rats and compared to pure drug. The stable nanosuspension was obtained with average size range of the precipitated nanoparticles between 150-300 nm and was found to be homogenous showing a narrow polydispersity index of 0.3±0.1. DSC and XRD studies indicated that the crystalline furosemide drug was converted to amorphous form upon precipitation into nanoparticles. The release profiles of nanosuspension formulation showed up to 81.2% release in 4 h. The in vivo studies on rats revealed a significant increase in the oral absorption of furosemide in the nanosuspension compared to pure drug. The AUC0→24 and Cmax values of nanosuspension were approximately 1.38 and 1.68-fold greater than that of pure drug, respectively. Furosemide nanosuspension showed 20.06±0.02 % decrease in systolic blood pressure compared to 13.37±0.02 % in plain furosemide suspension, respectively. The improved oral bioavailability and pharmacodynamics effect of furosemide may be due to the improved dissolution of furosemide in simulated gastric fluid which results in enhanced oral systemic absorption of furosemide from stomach region where it has better permeability.

Keywords: furosemide, nanosuspension, bioavailability enhancement, nanoprecipitation, oral drug delivery

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Authors: A. Newman-Tancredi, R. Depoortère, P. Gruca, E. Litwa, M. Lason, M. Papp

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The N-methyl-D-aspartic acid (NMDA) receptor antagonist, ketamine, can elicit rapid-acting antidepressant (RAAD) effects in treatment-resistant patients, but it requires parenteral co-administration with a classical antidepressant under medical supervision. In addition, ketamine can also produce serious side effects that limit its long-term use, and there is much interest in identifying RAADs based on ketamine’s mechanism of action but with safer profiles. Ketamine elicits GABAergic interneuron inhibition, glutamatergic neuron stimulation, and, notably, activation of serotonin 5-HT1A receptors in the prefrontal cortex (PFC). Direct activation of the latter receptor subpopulation with selective ‘biased agonists’ may therefore be a promising strategy to identify novel RAADs and, consistent with this hypothesis, the prototypical cortical biased agonist, NLX-101, exhibited robust RAAD-like activity in the chronic mild stress model of depression (CMS). The present study compared the effects of a novel, selective 5-HT1A receptor-biased agonist, NLX-204, with those of ketamine and NLX-101. Materials and methods: CMS procedure was conducted on Wistar rats; drugs were administered either intraperitoneally (i.p.) or by bilateral intracortical microinjection. Ketamine: 10 mg/kg i.p. or 10 µg/side in PFC; NLX-204 and NLX-101: 0.08 and 0.16 mg/kg i.p. or 16 µg/side in PFC. In addition, interaction studies were carried out with systemic NLX-204 or NLX-101 (each at 0.16 mg/kg i.p.) in combination with intracortical WAY-100635 (selective 5-HT1A receptor antagonist; 2 µg/side) or muscimol (GABA-A receptor agonist, 12.5 ng/side). Anhedonia was assessed by CMS-induced decrease in sucrose solution consumption; anxiety-like behavior was assessed using the Elevated Plus Maze (EPM), and cognitive impairment was assessed by the Novel Object Recognition (NOR) test. Results: A single administration of NLX-204 was sufficient to reverse the CMS-induced deficit in sucrose consumption, similarly to ketamine and NLX-101. NLX-204 also reduced CMS-induced anxiety in the EPM and abolished CMS-induced NOR deficits. These effects were maintained (EPM and NOR) or enhanced (sucrose consumption) over a subsequent 2-week period of treatment. The anti-anhedonic response of the drugs was also maintained for several weeks Following treatment discontinuation, suggesting that they had sustained effects on neuronal networks. A single PFC administration of NLX-204 reversed deficient sucrose consumption, similarly to ketamine and NLX-101. Moreover, the anti-anhedonic activities of systemic NLX-204 and NLX 101 were abolished by coadministration with intracortical WAY-100635 or muscimol. Conclusions: (i) The antidepressant-like activity of NLX-204 in the rat CMS model was as rapid as that of ketamine or NLX-101, supporting targeting cortical 5-HT1A receptors with selective, biased agonists to achieve RAAD effects. (ii)The anti-anhedonic activity of systemic NLX-204 was mimicked by local administration of the compound in the PFC, confirming the involvement of cortical circuits in its RAAD-like effects. (iii) Notably, the effects of systemic NLX-204 and NLX-101 were abolished by PFC administration of muscimol, indicating that they act by (indirectly) eliciting a reduction in cortical GABAergic neurotransmission. This is consistent with ketamine’s mechanism of action and suggests that there are converging NMDA and 5-HT1A receptor signaling cascades in PFC underlying the RAAD-like activities of ketamine and NLX-204. Acknowledgements: The study was financially supported by NCN grant no. 2019/35/B/NZ7/00787.

Keywords: depression, ketamine, serotonin, 5-HT1A receptor, chronic mild stress

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Authors: Morlu Stevens, Bareki Batlokwa

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The use of treated wastewater is widely employed to compensate for the scarcity of safe and uncontaminated freshwater. However, the existence of toxic heavy metal ions in the wastewater pose a health hazard to animals and the environment, hence, the importance for an effective technique to tackle the challenge. A multi-templated ion imprinted sorbent (Fe,Ni,Cu-IIP) for the simultaneous removal of heavy metal ions from waste water was synthesised employing molecular imprinting technology (MIT) via thermal free radical bulk polymerization technique. Methacrylic acid (MAA) was employed as the functional monomer, and ethylene glycol dimethylacrylate (EGDMA) as cross-linking agent, azobisisobutyronitrile (AIBN) as the initiator, Fe, Ni, Cu ions as template ions, and 1,10-phenanthroline as the complexing agent. The template ions were exhaustively washed off the synthesized polymer by solvent extraction in several washing steps, while periodically increasing solvent (HCl) concentration from 1.0 M to 10.0 M. The physical and chemical properties of the sorbents were investigated using Fourier Transform Infrared Spectroscopy (FT-IR), X-ray Diffraction (XRD) and Atomic Force Microscopy (AFM) were employed. Optimization of operational parameters such as time, pH and sorbent dosage to evaluate the effectiveness of sorbents were investigated and found to be 15 min, 7.5 and 666.7 mg/L respectively. Selectivity of ion-imprinted polymers and competitive sorption studies between the template and similar ions were carried out and showed good selectivity towards the targeted metal ion by removing 90% - 98% of the templated ions as compared to 58% - 62% of similar ions. The sorbents were further applied for the selective removal of Fe, Ni and Cu from real wastewater samples and recoveries of 92.14 ± 0.16% - 106.09 ± 0.17% and linearities of R2 = 0.9993 - R2 = 0.9997 were achieved.

Keywords: ion imprinting, ion imprinted polymers, heavy metals, wastewater

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Authors: Bruna C. Brasileiro, José Alberto S. Sá, Brigida R. P. Rocha

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The Amazon region development was related to large-scale projects associated with economic cycles. Economic cycles were originated from policies implemented by successive governments that exploited the resources and have not yet been able to improve the local population's quality of life. These implanted development strategies were based on vertical planning centered on State that didn’t know and showed no interest in know the local needs and potentialities. The future of this region is a challenge that depends on a model of development based on human progress associated to intelligent, selective and environmentally safe exploitation of natural resources settled in renewable and no-polluting energy generation sources – a differential factor of attraction of new investments in a context of global energy and environmental crisis. In this process the planning and support of Brazilian State, local government, and selective international partnership are essential. Residual biomass utilization allows the sustainable development by the integration of production chain and energy generation process which could improve employment condition and income of riversides. Therefore, this research discourses how the use of local residual biomass (açaí lumps) could be an important instrument of sustainable development for isolated communities located at Alcobaça Sustainable Development Reserve (SDR), Tucuruí, Pará State, since in this region the energy source more accessible for who can pay are the fossil fuels that reaches about 54% of final energy consumption by the integration between the açaí productive chain and the use of renewable energy source besides it can promote less environmental impact and decrease the use of fossil fuels and carbon dioxide emissions.

Keywords: Amazon, biomass, renewable energy, sustainability

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Authors: Heiko Scholz

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When feeding high qualitysilagetoheifersfromthe age of two, there is a riskofenergyoversupply. Depending on the feeding valueorscarceavailability ofsilageorcorn silage diets withhighproportionsof straw is often incorporated. Foran energetically standardized young cattle supply of strawproportion can be more than 20% of dry matter. It was investigated whether the grinding of straw with the strawmillselective feeding significantly limits. The investigation has been carried out with young cattle in the second year. 78 animals were kept and fed under similar conditions in two groups. The experimental group (EG) consisted of cattle 12 to 15 months, and in the control group (CG), the cattle were 15 to 20 months old. The experimental feeding took place in five days of feed distribution, and residual feed were weighed. The ration of EG contained ground with the straw mill straw, and CG was further fed rotor-cut pressed straw. To determine the selective seizure samples of feed distributionandtheremainingfood with the particle separator boxandthecrude protein-and energy-content have been determined. The grinding of the straw increased the daily feed intake.IntheEGan increase infeed intakewas observedby grinding of the straw. Feed intakedirectlyon the day for changing the dietoflongonground straw increased by more than 2.0 kgofDMper animal. In the following days, the feed intakewasincreasedby 0.9kg DMper animal and day on average (7.4 vs. 8.3 kg DM per day). The results of the screen distribution of residual feed point to a differentiated feeding behavior between the groups. In the EG, the particle length of the residual feed to a large extent with the template matches. The acid-base-balance (NSBA)valuesofEGarewithin normal limits. Ifstrawsharesof25% and more are federations to young cattle (heifers), the theparticlelengthof straw has significant impact ontheselectivefeeding behavior. Aparticlelength of 1.5cmcompared to7.5 cmlongpreventedstrawcertainly discarding of the straw on the feeding barn. The feed intake increases whenshortstrawis mixed into theTMR.

Keywords: straw mill, heifer, feed selection, dry matter intake

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Authors: Asis Kumar Khan, Rajeev Kumar Goel

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Recent infrastructure growth all around the world lead to increase in demand for concrete day by day. Cement being binding material for concrete the usage of cement also gone up significantly. Cement manufacturing utilizes abundant natural resources and causes environment pollution by releasing a huge quantity of CO₂ into the atmosphere. So, it is high time to look for alternates to reduce the cement consumption in concrete. Geopolymer concrete is one such material which utilizes the industrial waste such as fly ash, ground granulated blast furnace slag and low-cost alkaline liquids such as sodium hydroxide and sodium silicate to produce the concrete. On the other side, river sand is becoming very expensive due to its large-scale depletion at source and the high cost of transportation. In this view, river sand is replaced by crushed sand in this study. In this work, an attempt has been made to understand the durability parameters of geopolymer concrete by partially replacing fly ash with cement. Fly ash is replaced by cement at various levels e.g., from 0 to 50%. Concrete cubes of 100x100x100mm were used for investigating different durability parameters. The various parameters studied includes compressive strength, split tensile strength, drying shrinkage, sodium sulphate attack resistance, sulphuric acid attack resistance and chloride permeability. Highest compressive strength & highest split tensile strength is observed in 30% replacement level. Least drying is observed with 30% replacement level. Very good resistance for sulphuric acid & sodium sulphate is found with 30% replacement. However, it was not possible to find out the chloride permeability due to the high conductivity of geopolymer samples of all replacement levels.

Keywords: crushed sand, compressive strength, drying shrinkage, geopolymer concrete, split tensile strength, sodium sulphate attack resistance, sulphuric acid attack resistance

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Authors: Poojan Kothari, Yash Madhani, Chayan Jani, Bharti Saini

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The requirements for quality drinking and industrial water are increasing and water resources are depleting. Moreover large amount of wastewater is being generated and dumped into water bodies without treatment. These have made improvement in water treatment efficiency and its reuse, an important agenda. Membrane technology for wastewater treatment is an advanced process and has become increasingly popular in past few decades. There are many traditional methods for tertiary treatment such as chemical coagulation, adsorption, etc. However recent developments in membrane technology field have led to manufacturing of better quality membranes at reduced costs. This along with the high costs of conventional treatment processes, high separation efficiency and relative simplicity of the membrane treatment process has made it an economically viable option for municipal and industrial purposes. Ultrafiltration polymeric membranes can be used for wastewater treatment and drinking water applications. The proposed work focuses on preparation of one such UF membrane - Polyvinylidene fluoride (PVDF) doped with LiBr for wastewater treatment. Majorly all polymeric membranes are hydrophobic in nature. This property leads to repulsion of water and hence solute particles occupy the pores, decreasing the lifetime of a membrane. Thus modification of membrane through addition of small amount of salt such as LiBr helped us attain certain characteristics of membrane, which can then be used for wastewater treatment. The membrane characteristics are investigated through measuring its various properties such as porosity, contact angle and wettability to find out the hydrophilic nature of the membrane and morphology (surface as well as structure). Pure water flux, solute rejection and permeability of membrane is determined by permeation experiments. A study of membrane characteristics with various concentration of LiBr helped us to compare its effectivity.

Keywords: Lithium bromide (LiBr), morphology, permeability, Polyvinylidene fluoride (PVDF), solute rejection, wastewater treatment

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Authors: Sotirios Longinos, Anna Loskutova, Assel Tolegenova, Assem Imanzhussip, Lei Wang

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Hot, dry rock (HDR) has substantial potential as a thermal energy source. It has been exploited by hydraulic fracturing to extract heat and generate electricity, which is a well-developed technique known for creating the enhanced geothermal systems (EGS). These days, LN2 is being tested as an environmental friendly fracturing fluid to generate densely interconnected crevices to augment heat exchange efficiency and production. This study examines experimentally the efficacy of LN2 cryogenic fracturing for granite samples in Kazakhstan with immersion method. A comparison of two different experimental models is carried out. The first mode is rock heating along with liquid nitrogen treatment (heating with freezing time), and the second mode is multiple times of heating along with liquid nitrogen treatment (heating with LN2 freezing-thawing cycles). The experimental results indicated that with multiple heating and LN2-treatment cycles, the permeability of granite first ameliorates with increasing number of cycles and later reaches a plateau after a certain number of cycles. On the other hand, density, P-wave velocity, uniaxial compressive strength, elastic modulus, and tensile strength indicate a downward trend with increasing heating and treatment cycles. The thermal treatment cycles do not seem to have an obvious effect on the Poisson’s ratio. The changing rate of granite rock properties decreases as the number of cycles increases. The deterioration of granite primarily happens within the early few cycles. The heating temperature during the cycles shows an important influence on the deterioration of granite. More specifically, mechanical deterioration and permeability amelioration become more remarkable as the heating temperature increases.LN2 fracturing generates many positives compared to conventional fracturing methods such as little water consumption, requirement of zero chemical additives, lessening of reservoir damage, and so forth. Based on the experimental observations, LN2 can work as a promising waterless fracturing fluid to stimulate hot, dry rock reservoirs.

Keywords: granite, hydraulic fracturing, liquid nitrogen, Kazakhstan

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Authors: P. Raajeswari, S. M. Devatha, R. Pragatheeswari

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The edible packaging is a new trendsetter in the era of modern packaging. The researchers and food scientist recognise edible packaging as a useful alternative or addition to conventional packaging to reduce waste and to create novel applications for improving product stability. Starch was extracted from different sources that contains abundantly like potato, tapioca, rice, wheat, and corn. The starch based edible films and cutleries are developed as an alternative for conventional packages providing the nutritional benefit when consumed along with the food. The development of starch based edible films by the extraction of starch from various raw ingredients at lab scale level. The films are developed by the employment of plasticiser at different concentrations of 1.5ml and 2ml. The films developed using glycerol as a plasticiser in filmogenic solution to increase the flexibility and plasticity of film. It reduces intra and intermolecular forces in starch, and it increases the mobility of starch based edible films. The films developed are tested for its functional properties such as thickness, tensile strength, elongation at break, moisture permeability, moisture content, and puncture strength. The cutleries like spoons and cups are prepared by making dough and rolling the starch along with water. The overall results showed that starch based edible films absorbed less moisture, and they also contributed to the low moisture permeability with high tensile strength. Food colorants extracted from red onion peel, pumpkin, and red amaranth adds on the nutritive value, colour, and attraction when incorporated in edible cutleries, and it doesn’t influence the functional properties. Addition of a low quantity of glycerol in edible films and colour extraction from onion peel, pumpkin, and red amaranth enhances biodegradability and provides a good quantity of nutrients when consumed. Therefore, due to its multiple advantages, food starch can serve as the best response for eco-friendly industrial products aimed to replace single use plastics at low cost.

Keywords: edible films, edible cutleries, plasticizer, glycerol, starch, functional property

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Authors: Waldir Roque, Gustavo Oliveira, Moises Santos, Tatiana Simoes

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Increasing the oil recovery factor of an oil reservoir has been a concern of the oil industry. Usually, the production placement zones are defined after some analysis of geological and petrophysical parameters, being the rock porosity, permeability and oil saturation of fundamental importance. In this context, the determination of hydraulic flow units (HFUs) renders an important step in the process of reservoir characterization since it may provide specific regions in the reservoir with similar petrophysical and fluid flow properties and, in particular, techniques supporting the placement of production zones that favour the tracing of directional wells. A HFU is defined as a representative volume of a total reservoir rock in which petrophysical and fluid flow properties are internally consistent and predictably distinct of other reservoir rocks. Technically, a HFU is characterized as a rock region that exhibit flow zone indicator (FZI) points lying on a straight line of the unit slope. The goal of this paper is to provide a trustful indication for oil production placement zones for the best-fit HFUs. The FZI cloud of points can be obtained from the reservoir quality index (RQI), a function of effective porosity and permeability. Considering log and core data the HFUs are identified and using the discrete rock type (DRT) classification, a set of connected cell clusters can be found and by means a graph centrality metric, the maximum closeness (MaxC) cell is obtained for each cluster. Considering the MaxC cells as production zones, an extensive analysis, based on several oil recovery factor and oil cumulative production simulations were done for the SPE Model 2 and the UNISIM-I-D synthetic fields, where the later was build up from public data available from the actual Namorado Field, Campos Basin, in Brazil. The results have shown that the MaxC is actually technically feasible and very reliable as high performance production placement zones.

Keywords: hydraulic flow unit, maximum closeness centrality, oil production simulation, production placement zone

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Authors: Azad Jarrahian, Ehsan Heidaryan

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Matrix acidizing treatments can yield impressive production increase if properly applied. In this study, carbonate samples taken from Ahwaz Oilfield have undergone static solubility, sludge, emulsion, and core flooding tests. In each test interaction of acid and rock is reported and at the end it has been shown that how initial permeability and type of acid affects the overall treatment efficiency.

Keywords: carbonate acidizing, organic acids, spending rate, acid penetration, incomplete spending.

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Authors: Waqas Ashraf, Yasir Nawab, Haritham Khan, Habib Awais, Shahbaz Ahmad

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Seersucker is a popular lightweight fabric widely used in men’s and women’s suiting, casual wear, children’s clothing, house robes, bed spreads and for spring and summer wear. The puckered effect generates air spaces between body and the fabric, keeping the wearer cool in hot conditions. The aim of this work was to develop knitted seersucker fabric on single cylinder weft knitting machine using plain jersey structure. Core spun cotton yarn and cotton spun yarn of same linear density were used. Core spun cotton yarn, contains cotton fiber in the sheath and elastase filament in the core. The both yarn were fed at regular interval to feeders on the machine. The loop length and yarn tension were kept constant at each feeder. The samples were then scoured and bleached. After wet processing, the fabric samples were washed and tumble dried. Parameters like loop length, stitch density and areal density were measured after conditioning these samples for 24 hours in Standard atmospheric condition. Produced sample has a regular puckering stripe along the width of the fabric with same height. The stitch density of both the flat and puckered area of relaxed fabric was found to be different .Air permeability and moisture management tests were performed. The results indicated that the knitted seersucker fabric has better wicking and moisture management properties as the flat area contact, whereas puckered area held away from the skin. Seersucker effect in knitted fabric was achieved by the difference of contraction of both sets of courses produced from different types of yarns. The seer sucker fabric produce by knitting technique is less expensive as compared to woven seer sucker fabric as there is no need of yarn preparation. The knitted seersucker fabric is more practicable for summer dresses, skirts, blouses, shirts, trousers and shorts.

Keywords: air permeability, knitted structure, moisture management, seersucker

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Authors: Valeriy M. Kondratev, Ekaterina A. Vyacheslavova, Talgat Shugabaev, Alexander S. Gudovskikh, Alexey D. Bolshakov

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Modern sensorics imposes strict requirements on the biosensors characteristics, especially technological feasibility, and selectivity. There is a growing interest in the analysis of human health biological markers, which indirectly testifying the pathological processes in the body. Such markers are acids and alkalis produced by the human, in particular - ammonia and hydrochloric acid, which are found in human sweat, blood, and urine, as well as in gastric juice. Biosensors based on modern nanomaterials, especially low dimensional, can be used for this markers detection. Most classical adsorption sensors based on metal and silicon oxides are considered non-selective, because they identically change their electrical resistance (or impedance) under the action of adsorption of different target analytes. This work demonstrates a feasible frequency-resistive method of electrical impedance spectroscopy data analysis. The approach allows to obtain of selectivity in adsorption sensors of a resistive type. The method potential is demonstrated with analyzis of impedance spectra of silicon nanowires in the presence of NH3 and HCl vapors with concentrations of about 125 mmol/L (2 ppm) and water vapor. We demonstrate the possibility of unambiguous distinction of the sensory signal from NH3 and HCl adsorption. Moreover, the method is found applicable for analysis of the composition of ammonia and hydrochloric acid vapors mixture without water cross-sensitivity. Presented silicon sensor can be used to find diseases of the gastrointestinal tract by the qualitative and quantitative detection of ammonia and hydrochloric acid content in biological samples. The method of data analysis can be directly translated to other nanomaterials to analyze their applicability in the field of biosensory.

Keywords: electrical impedance spectroscopy, spectroscopy data analysis, selective adsorption sensor, nanotechnology

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Authors: Daniel Monsalve, Takafumi Noguchi

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Mycelium-based composites (MBC) are made by growing living mycelium on lignocellulosic fibres to create a porous composite material which can be lightweight, and biodegradable, making them suitable as a sustainable thermal insulation. Thus, they can help to reduce material extraction while improving the energy efficiency of buildings, especially when agricultural by-products are used. However, as MBC are hygroscopic materials, moisture can reduce their thermal insulation efficiency. It is known that surface growth, or “mycelium skin”, can form a natural coating due to the hydrophobic properties in the mycelium cell wall. Therefore, this research aims to biofabricate a homogeneous mycelium skin and measure its influence on the final composite material by testing material properties such as thermal conductivity, vapour permeability and water absorption by partial immersion over 24 hours. In addition, porosity, surface morphology and chemical composition were also analyzed. The white-rot fungi species Pleurotus ostreatus, Ganoderma lucidum, and Trametes versicolor were grown on 10 mm hemp fibres (Cannabis sativa), and three different biofabrication protocols were used during incubation, varying the time and surface treatment, including the addition of pre-colonised sawdust. The results indicate that density can be reduced by colonisation time, which will favourably impact thermal conductivity but will negatively affect vapour and liquid water control. Additionally, different fungi can exhibit different resistance to prolonged water absorption, and due to osmotic sensitivity, mycelium skin may also diminish moisture control. Finally, a collapse in the mycelium network after water immersion was observed through SEM, indicating how the microstructure is affected, which is also dependent on fungi species and the type of skin achieved. These results help to comprehend the differences and limitations of three of the most common species used for MBC fabrication and how precise engineering is needed to effectively control the material output.

Keywords: mycelium, thermal conductivity, vapor permeability, water absorption

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Authors: Shimayali Kaushal, Nitesh Priyadarshi, Nitin Kumar Singhal

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Food borne bacterial species have been identified as major pathogens in most of the severe pathogen-related diseases among humans which result in great loss to human health and food industry. Conventional methods like plating and enzyme-linked immune sorbent assay (ELISA) are time-consuming, laborious and require specialized instruments. Nanotechnology has emerged as a great field in case of rapid detection of pathogens in recent years. The AuNRs material has good electro-optical properties due to its larger light absorption band and scattering in surface plasmon resonance wavelength regions. By exploiting the sugar-based adhesion properties of microorganism, we can use the glycoconjugates capped gold nanorods as a potential nanobiosensor to detect the foodborne pathogen. In the present study, polyethylene glycol (PEG) coated gold nanorods (AuNRs) were prepared and functionalized with different types of carbohydrates and further characterized by UV-Visible spectrophotometry, dynamic light scattering (DLS), transmission electron microscopy (TEM). The reactivity of above said nano-biosensor was probed by lectin binding assay and also by different strains of foodborne bacteria by using spectrophotometric and microscopic techniques. Due to the specific interaction of probe with foodborne bacteria (Escherichia coli, Pseudomonas aeruginosa), our nanoprobe has shown significant and selective ablation of targeted bacteria. Our findings suggest that our nanoprobe can be an ideal candidate for selective optical detection of food pathogens and can reduce loss to the food industry.

Keywords: glyco-conjugates, gold nanorods, nanobiosensor, nanoprobe

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Authors: Riaz A. Agha, Alexander J. Fowler, Seon-Young Lee, Buket Gundogan, Katharine Whitehurst, Harkiran K. Sagoo, Kyung Jin Lee Jeong, Douglas G. Altman, Dennis P. Orgill

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Introduction: Case Series are an important and common study type. Currently, no guideline exists for reporting case series and there is evidence of key data being missed from such reports. We propose to develop a reporting guideline for case series using a methodologically robust technique. The first step in this process is a systematic review of literature relevant to the reporting deficiencies of case series. Methods: A systematic review of methodological and reporting quality in surgical case series was performed. The electronic search strategy was developed by an information specialist and included MEDLINE, EMBASE, Cochrane Methods Register, Science Citation index and Conference Proceedings Citation index, from the start of indexing until 5th November 2014. Independent screening, eligibility assessments and data extraction was performed. Included articles were analyzed for five areas of deficiency: failure to use standardized definitions missing or selective data transparency or incomplete reporting whether alternate study designs were considered. Results: The database searching identified 2,205 records. Through the process of screening and eligibility assessments, 92 articles met inclusion criteria. Frequency of methodological and reporting issues identified was a failure to use standardized definitions (57%), missing or selective data (66%), transparency, or incomplete reporting (70%), whether alternate study designs were considered (11%) and other issues (52%). Conclusion: The methodological and reporting quality of surgical case series needs improvement. Our data shows that clear evidence-based guidelines for the conduct and reporting of a case series may be useful to those planning or conducting them.

Keywords: case series, reporting quality, surgery, systematic review

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Authors: Lidya Hailu, Ramesh Duraisamy, Masood Akhtar Khan, Belete Yilma

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Disposable food packaging is a single-use plastics that can include any disposable plastic item which could be designed and use only once. In this context, this study aimed to prepare and evaluate bioplastic food packaging material from avocado seed starch and sugarcane bagasse cellulose and to characterise avocado seed starch. Performed the physicomechanical, structural, thermal properties, and biodegradability of raw materials and readily prepared bioplastic using the universal tensile testing machine, FTIR, UV-Vis spectroscopy, TGA, XRD, and SEM. Results have shown that an increasing amount of glycerol (3-5 mL) resulted in increases in water absorption, density, water vapor permeability, and elongation at the break of prepared bioplastic. However, it causes decreases in % transmittance, thermal degradation, and the tensile strength of prepared bioplastic. Likewise, the addition of cellulose fiber (0-15 %) increases % transmittance ranged (91.34±0.12-63.03±0.05 %), density (0.93±0.04-1.27±0.02 g/cm3), thermal degradation (310.01-321.61°C), tensile strength (2.91±6.18-4.21±6.713 MPa) of prepared bioplastic. On the other hand, it causes decreases in water absorption (14.4±0.25-9.40±0.007 %), water vapor permeability (9.306x10-12±0.3-3.57x10-12±0.15 g•s−1•m−1•Pa−1) and elongation at break (34.46±3.37-27.63±5.67 %) of prepared bioplastic. All the readily prepared bioplastic films rapidly degraded in the soil in the first 6 days and decompose within 12 days with a diminutive leftover and completely degraded within 15 days under an open soil atmosphere. Studied results showed starch derived bioplastic reinforced with 15 % cellulose fiber that plasticized with 3 mL of glycerol had improved results than other combinations of glycerol and bagasse cellulose with avocado seed starch. Thus, biodegradable disposable food packaging cup has been successfully produced in the lab-scale level using the studied approach. Biodegradable disposable food packaging materials have been successfully produced by employing avocado seed starch and sugarcane bagasse cellulose. The future study should be done on nano scale production since this study was done at the micro level.

Keywords: avocado seed, food packaging, glycerol, sugarcane bagasse

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Authors: Blaga Alexandra Cristina, Kloetzer Lenuta, Bompa Amalia Stela, Galaction Anca Irina, Cascaval Dan

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Vitamin B9 is an important member of vitamins B group, being a growth factor, important for making genetic material as DNA and RNA, red blood cells, for building muscle tissues, especially during periods of infancy, adolescence and pregnancy. Its production by biosynthesis is based on the high metabolic potential of mutant Bacillus subtilis, due to a superior biodisponibility compared to that obtained by chemical pathways. Pertraction, defined as the extraction and transport through liquid membranes consists in the transfer of a solute between two aqueous phases of different pH-values, phases that are separated by a solvent layer of various sizes. The pertraction efficiency and selectivity could be significantly enhanced by adding a carrier in the liquid membrane, such as organophosphoric compounds, long chain amines or crown-ethers etc., the separation process being called facilitated pertraction. The aim of the work is to determine the impact of the presence of two extractants/carriers in the bulk liquid membrane, i.e. di(2-ethylhexyl) phosphoric acid (D2EHPA) and lauryltrialkylmetilamine (Amberlite LA2) on the transport kinetics of vitamin B9. The experiments have been carried out using two pertraction equipments for a free liquid membrane or bulk liquid membrane. One pertraction cell consists on a U-shaped glass pipe (used for the dichloromethane membrane) and the second one is an H-shaped glass pipe (used for h-heptane), having 45 mm inner diameter of the total volume of 450 mL, the volume of each compartment being of 150 mL. The aqueous solutions are independently mixed by means of double blade stirrers with 6 mm diameter and 3 mm height, having the rotation speed of 500 rpm. In order to reach high diffusional rates through the solvent layer, the organic phase has been mixed with a similar stirrer, at a similar rotation speed (500 rpm). The area of mass transfer surface, both for extraction and for reextraction, was of 1.59x10-³ m2. The study on facilitated pertraction with the mixture of two carriers, namely D2EHPA and Amberlite LA-2, dissolved in two solvents with different polarities: n-heptane and dichloromethane, indicated the possibility to obtain the synergic effect. The synergism has been analyzed by considering the vitamin initial and final mass flows, as well as the permeability factors through liquid membrane. The synergic effect has been observed at low D2EHPA concentrations and high Amberlite LA-2 concentrations, being more important for the low-polar solvent (n-heptane). The results suggest that the mechanism of synergic pertraction consists on the reaction between the organophosphoric carrier and vitamin B9 at the interface between the feed and membrane phases, while the aminic carrier enhances the hydrophobicity of this compound by solvation. However, the formation of this complex reduced the reextraction rate and, consequently, affects the synergism related to the final mass flows and permeability factor. For describing the influences of carriers concentrations on the synergistic coefficients, some equations have been proposed by taking into account the vitamin mass flows or permeability factors, with an average deviations between 4.85% and 10.73%.

Keywords: pertraction, synergism, vitamin B9, Amberlite LA-2, di(2-ethylhexyl) phosphoric acid

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Authors: Claudia Matassa, Matthias Hohne, Dominic Ormerod, Yamini Satyawali

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Chiral amines integrate the backbone of several active pharmaceutical ingredients (APIs) used in modern medicine for the treatment of a vast range of diseases. Despite the demand, their synthesis remains challenging. Besides a range of chemicals and enzymatical methods, chiral amine synthesis using transaminases (EC 2.6.1.W) represents a useful alternative to access this important class of compounds. Even though transaminases exhibit excellent stereo and regioselectivity and the potential for high yield, the reaction suffers from a number of challenges, including the thermodynamic equilibrium, product inhibition, and low substrate solubility. In this work, we demonstrate a membrane assisted strategy for addressing these challenges. It involves the use of high molecular weight (HMW) amine donors for the transaminase-catalyzed synthesis of 4-phenyl-2-butylamine in both aqueous and organic solvent media. In contrast to common amine donors such as alanine or isopropylamine, these large molecules, provided in excess for thermodynamic equilibrium shifting, are easily retained by commercial nanofiltration membranes; thus a selective permeation of the desired smaller product amine is possible. The enzymatic transamination in aqueous media, combined with selective product removal shifted the equilibrium enhancing substrate conversion by an additional 25% compared to the control reaction. Along with very efficient amine product removal, there was undesirable loss of ketone substrate and low product concentration was achieved. The system was therefore further improved by performing the reaction in organic solvent (n-heptane). Coupling the reaction system with membrane-assisted product removal resulted in a highly concentrated and relatively pure ( > 97%) product solution. Moreover, a product yield of 60% was reached, compared to 15% without product removal.

Keywords: amine donor, chiral amines, in situ product removal, transamination

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Authors: Antoifi Abdoulhalik, Ashraf Ahmed

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Saltwater intrusion (SWI) in coastal aquifers has become a growing threat for many countries around the world. While various control measures have been suggested to mitigate SWI, the construction of subsurface physical barriers remains one of the most effective solutions for this problem. In this work, we used laboratory experiments and numerical simulations to investigate the effectiveness of subsurface dams in heterogeneous layered coastal aquifer with different layering patterns. Four different cases were investigated, including a homogeneous (case H), and three heterogeneous cases in which a low permeability (K) layer was set in the top part of the system (case LH), in the middle part of the system (case HLH) and the bottom part of the system (case HL). Automated image analysis technique was implemented to quantify the main SWI parameters under high spatial and temporal resolution. The method also provides transient salt concentration maps, allowing for the first time clear visualization of the spillage of saline water over the dam (advancing wedge condition) as well as the flushing of residual saline water from the freshwater area (receding wedge condition). The SEAWAT code was adopted for the numerical simulations. The results show that the presence of an overlying layer of low permeability enhanced the ability of the dam to retain the saline water. In such conditions, the rate of saline water spillage and inland extension may considerably be reduced. Conversely, the presence of an underlying low K layer led to a faster increase of saltwater volume on the seaward side of the wall, therefore considerably facilitating the spillage. The results showed that a complete removal of the residual saline water eventually occurred in all the investigated scenarios, with a rate of removal strongly affected by the hydraulic conductivity of the lower part of the aquifer. The data showed that the addition of the underlying low K layer in case HL caused the complete flushing to be almost twice longer than in the homogeneous scenario.

Keywords: heterogeneous coastal aquifers, laboratory experiments, physical barriers, seawater intrusion control

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Authors: Sara Franco Ortega, Alina Goldberg Cavalleri, Nawaporn Onkokesung, Richard Dale, Melissa Brazier-Hicks, Robert Edwards

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Safeners are agrochemicals that enhance the selective chemical control of wild grasses by increasing the ability of the crop to metabolise the herbicide. Although these compounds are widely used, their mode of action is not well understood. It is known that safeners enhance the metabolism of herbicides, by up-regulating the associated detoxification system we have termed the xenome. The xenome proteins involved in herbicide metabolism have been previously divided into four different phases, with cytochrome P450s (CYPs) playing a key role in phase I metabolism by catalysing hydroxylation and dealkylation reactions. Subsequently, glutathione S-transferases (GSTs) and UDP-glucosyltransferases lead to the formation of Phase II conjugates prior to their transport into the vacuole by ABCs transporters (Phase III). Maize (Zea mays), was been treated with different safeners to explore the selective induction of xenome proteins, with a special interest in the regulation of the CYP superfamily. Transcriptome analysis enabled the identification of key safener-inducible CYPs that were then functionally assessed to determine their role in herbicide detoxification. In order to do that, CYP’s were codon optimised, synthesised and inserted into the yeast expression vector pYES3 using in-fusion cloning. CYP’s expressed as recombinant proteins in a strain of yeast engineered to contain the P450 co-enzyme (cytochrome P450 reductase) from Arabidopsis. Microsomes were extracted and treated with herbicides of different chemical classes in the presence of the cofactor NADPH. The reaction products were then analysed by LCMS to identify any herbicide metabolites. The results of these studies will be presented with the key CYPs identified in maize used as the starting point to find orthologs in other crops and weeds to better understand their roles in herbicide selectivity and safening.

Keywords: CYPs, herbicide detoxification, LCMS, RNA-Seq, safeners

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Authors: Viktoriia Burkina, Vladimir Zlabek, Galia Zamaratskaia

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Cytochromes P450 (CYP) are important family of enzymes in Phase I metabolism. Environmental pollutants often act as inducers of the gene expression and activities CYP1A1 and CYP3A-like isoforms in fish. The activities are generally measured in the fish liver or gills, and less is known about tissue distribution of expression. In present study, the CYP1A1 and CYP3A-like activities were measured in rainbow trout liver, gill, intestine, heart, brain and gonads. The activities of CYP1A1 and CYP3A-like proteins were estimated as the rates of 7-ethoxyresorufin-O-deethylation (EROD) and benzyloxy-4-trifluoromethylcoumarin-O-debenzyloxylation (BFCOD), respectively. The CYP1A1 and CYP3A-like activities were detectable in all investigated fish tissues, with the highest activity in hepatic tissue followed by heart > brain > gill > intestine > gonads. To confirm the presence of CYP1A1 in different tissues, EROD activity was measured in presence of the selective inhibitors ellipticine (CYP1A1), ketoconazole (CYP3A), 8-methoxypsoralen (human CYP2A) and diallyl sulphide (CYP2E1). It was found that ellipticine, ketoconazole and 8-methoxypsoralen inhibited hepatic EROD activity by 88-98%. Ellipticine inhibited gill, intestine, and gonad EROD activity by 50%. In conclusion, EROD and BFCOD activities were detected in rainbow trout liver, gill, intestine, heart, brain and gonads. Further studies are needed to fully identify all CYP450 isoforms responsible for these activities. Acknowledgement: The study was financially supported by the Ministry of Education, Youth and Sports of the Czech Republic - projects „CENAKVA “(No. CZ.1.05/2.1.00/01.0024), “CENAKVA Center Development “(No. CZ.1.05/2.1.00/19.0380), “CENAKVA II “(No. LO1205 under the NPU I program), and "Development of USB - International mobility (No. CZ.02.2.69/0.0/0.0/16_027/0008364).

Keywords: BFCOD, EROD, fish, phase I metabolism, selective inhibitors

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Authors: Natalia V. Beloglazova, Pieterjan Lenain, Martin Hedstrom, Dietmar Knopp, Sarah De Saeger

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In recent years polycyclic aromatic hydrocarbons (PAHs), which represent a hazard to humans and entire ecosystem, have been receiving an increased interest due to their mutagenic, carcinogenic and endocrine disrupting properties. They are formed in all incomplete combustion processes of organic matter and, as a consequence, ubiquitous in the environment. Benzo(a)pyrene (BaP) is on the priority list published by the Environmental Agency (US EPA) as the first PAH to be identified as a carcinogen and has often been used as a marker for PAHs contamination in general. It can be found in different types of water samples, therefore, the European Commission set up a limit value of 10 ng L–1 (10 ppt) for BAP in water intended for human consumption. Generally, different chromatographic techniques are used for PAHs determination, but these assays require pre-concentration of analyte, create large amounts of solvent waste, and are relatively time consuming and difficult to perform on-site. An alternative robust, stand-alone, and preferably cheap solution is needed. For example, a sensing unit which can be submerged in a river to monitor and continuously sample BaP. An affinity sensor based on capacitive transduction was developed. Natural antibodies or their synthetic analogues can be used as ligands. Ideally the sensor should operate independently over a longer period of time, e.g. several weeks or months, therefore the use of molecularly imprinted polymers (MIPs) was discussed. MIPs are synthetic antibodies which are selective for a chosen target molecule. Their robustness allows application in environments for which biological recognition elements are unsuitable or denature. They can be reused multiple times, which is essential to meet the stand-alone requirement. BaP is a highly lipophilic compound and does not contain any functional groups in its structure, thus excluding non-covalent imprinting methods based on ionic interactions. Instead, the MIPs syntheses were based on non-covalent hydrophobic and π-π interactions. Different polymerization strategies were compared and the best results were demonstrated by the MIPs produced using electropolymerization. 4-vinylpyridin (VP) and divinylbenzene (DVB) were used as monomer and cross-linker in the polymerization reaction. The selectivity and recovery of the MIP were compared to a non-imprinted polymer (NIP). Electrodes were functionalized with natural receptor (monoclonal anti-BaP antibody) and with MIPs selective towards BaP. Different sets of electrodes were evaluated and their properties such as sensitivity, selectivity and linear range were determined and compared. It was found that both receptor can reach the cut-off level comparable to the established ML, and despite the fact that the antibody showed the better cross-reactivity and affinity, MIPs were more convenient receptor due to their ability to regenerate and stability in river till 7 days.

Keywords: antibody, benzo(a)pyrene, capacitive sensor, MIPs, river water

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Authors: A. Aslihan Gokaltun, Martin L. Yarmush, Ayse Asatekin, O. Berk Usta

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Poly(dimethylsiloxane) (PDMS) is one of the most widely used materials in the fabrication of microfluidic devices. It is easily patterned and can replicate features down to nanometers. Its flexibility, gas permeability that allows oxygenation, and low cost also drive its wide adoption. However, a major drawback of PDMS is its hydrophobicity and fast hydrophobic recovery after surface hydrophilization. This results in significant non-specific adsorption of proteins as well as small hydrophobic molecules such as therapeutic drugs limiting the utility of PDMS in biomedical microfluidic circuitry. While silicon, glass, and thermoplastics have been used, they come with problems of their own such as rigidity, high cost, and special tooling needs, which limit their use to a smaller user base. Many strategies to alleviate these common problems with PDMS are lack of general practical applicability, or have limited shelf lives in terms of the modifications they achieve. This restricts large scale implementation and adoption by industrial and research communities. Accordingly, we aim to tailor biocompatible PDMS surfaces by developing a simple and one step bulk modification approach with novel smart materials to reduce non-specific molecular adsorption and to stabilize long-term cell analysis with PDMS substrates. Smart polymers that blended with PDMS during device manufacture, spontaneously segregate to surfaces when in contact with aqueous solutions and create a < 1 nm layer that reduces non-specific adsorption of organic and biomolecules. Our methods are fully compatible with existing PDMS device manufacture protocols without any additional processing steps. We have demonstrated that our modified PDMS microfluidic system is effective at blocking the adsorption of proteins while retaining the viability of primary rat hepatocytes and preserving the biocompatibility, oxygen permeability, and transparency of the material. We expect this work will enable the development of fouling-resistant biomedical materials from microfluidics to hospital surfaces and tubing.

Keywords: cell culture, microfluidics, non-specific protein adsorption, PDMS, smart polymers

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Authors: Bahar Tunctan, Sefika Pinar Kucukkavruk, Meryem Temiz-Resitoglu, Demet Sinem Guden, Ayse Nihal Sari, Seyhan Sahan-Firat

Abstract:

We hypothesized that rexinoids such as bexarotene, a selective retinoid X receptor α (RXRα) agonist, may be beneficial for preventing mortality due to inflammation associated with increased expression/activity of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS). Therefore, we investigated effects of bexarotene on the changes in circulating protein levels of iNOS (an index for systemic iNOS expression), myeloperoxidase (MPO) (an index for systemic inflammation), and lactate dehydrogenase (LDH) (an index for systemic tissue injury) in LPS-induced systemic inflammation model resulting in septic shock in rats. Rats were injected with saline (4 ml/kg; i.p.), LPS (10 mg/kg; i.p.), dimethylsulphoxide (4 ml/kg, 0.1%; s.c.) at time 0. Mean arterial blood pressure and heart rate were measured using a tail-cuff device. Bexarotene (0.03, 0.1, 0.3, and 1 mg/kg; s.c.) was administered to separate groups of rats 1 h after injection of saline or LPS. The rats were sacrificed 4 h after saline or LPS injection and blood was collected for measurement of serum iNOS, MPO, and LDH protein levels. Blood pressure decreased by 31 mmHg and heart rate increased by 63 bpm in the LPS-treated rats. Bexarotene at 0.3 and 1 mg/kg doses caused 20% mortality 4 h after LPS injection. In the LPS-treated rats, serum iNOS, MPO, and LDH protein levels were increased. Bexarotene only at 0.1 mg/kg dose prevented the LPS-induced hypotension and increased in iNOS, MPO, and LDH protein levels. These data are consistent with the view that a decrease in systemic iNOS levels contributes to the beneficial effect of bexarotene to prevent the hypotension associated with inflammation and tissue injury during rat endotoxemia. [This work was financially supported by The Scientific and Technological Research Council of Turkey (SBAG-109S121)].

Keywords: bexarotene, inflammation, iNOS, lipopolisaccharide, RXRa

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Authors: Yang Yang, Luciana Magalhães Rebelo Alencar, Martha Sahylí Ortega Pijeira, Beatriz da Silva Batista, Alefe Roger Silva França, Erick Rafael Dias Rates, Ruana Cardoso Lima, Sara Gemini-Piperni, Ralph Santos-Oliveira

Abstract:

Radium-²²³ dichloride ([²²³Rₐ]RₐCl₂) is an alpha particle-emitting radiopharmaceutical currently approved for the treatment of patients with castration-resistant prostate cancer, symptomatic bone metastases, and no known visceral metastatic disease. [²²³Rₐ]RₐCl₂ is bone-seeking calcium mimetic that bonds into the newly formed bone stroma, especially osteoblastic or sclerotic metastases, killing the tumor cells by inducing DNA breaks in a potent and localized manner. Nonetheless, the successful therapy of osteosarcoma as primary bone tumors is still a challenge. Nanomicelles are colloidal nanosystems widely used in drug development to improve blood circulation time, bioavailability, and specificity of therapeutic agents, among other applications. In addition, the enhanced permeability and retention effect of the nanosystems, and the renal excretion of the nanomicelles reported in most cases so far, are very attractive to achieve selective and increased accumulation in tumor site as well as to increase the safety of [²²³Rₐ]RₐCl₂ in the clinical routine. In the present work, [²²³Rₐ]RₐCl₂ nanomicelles were produced, characterized, in vitro evaluated, and compared with pure [²²³Rₐ]RₐCl2 solution using SAOS2 osteosarcoma cells. The [²²³Rₐ]RₐCl₂ nanomicelles were prepared using the amphiphilic copolymer Pluronic F127. The dynamic light scattering analysis of freshly produced [²²³Rₐ]RₐCl₂ nanomicelles demonstrated a mean size of 129.4 nm with a polydispersity index (PDI) of 0.303. After one week stored in the refrigerator, the mean size of the [²²³Rₐ]RₐCl₂ nanomicelles increased to 169.4 with a PDI of 0.381. Atomic force microscopy analysis of [223Rₐ]RₐCl₂ nanomicelles exhibited spherical structures whose heights reach 1 µm, suggesting the filling of 127-Pluronic nanomicelles with [²²³Rₐ]RₐCl₂. The viability assay with [²²³Rₐ]RₐCl₂ nanomicelles displayed a dose-dependent response as it was observed using pure [²²³Rₐ]RₐCl2. However, at the same dose, [²²³Rₐ]RₐCl₂ nanomicelles were 20% higher efficient in killing SAOS2 cells when compared with pure [²²³Rₐ]RₐCl₂. These findings demonstrated the effectiveness of the nanosystem validating the application of nanotechnology in targeted alpha therapy with [²²³Ra]RₐCl₂. In addition, the [²²³Rₐ]RaCl₂nanomicelles may be decorated and incorporated with a great variety of agents and compounds (e.g., monoclonal antibodies, aptamers, peptides) to overcome the limited use of [²²³Ra]RₐCl₂.

Keywords: nanomicelles, osteosarcoma, radium dichloride, targeted alpha therapy

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