Search results for: titanium oxide nanoparticles

Authors: Deepak Loura

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Climate change is considered one of the major environmental problems of the 21st century and a lasting change in the statistical distribution of weather patterns over periods ranging from decades to millions of years. Agriculture and climate change are internally correlated with each other in various aspects, as the threat of varying global climate has greatly driven the attention of scientists, as these variations are imparting a negative impact on global crop production and compromising food security worldwide. The fast pace of development and industrialization and indiscriminate destruction of the natural environment, more so in the last century, have altered the concentration of atmospheric gases that lead to global warming. Carbon dioxide (CO₂), methane (CH₄), and nitrous oxide (NO) are important biogenic greenhouse gases (GHGs) from the agricultural sector contributing to global warming and their concentration is increasing alarmingly. Agricultural productivity can be affected by climate change in 2 ways: first, directly, by affecting plant growth development and yield due to changes in rainfall/precipitation and temperature and/or CO₂ levels, and second, indirectly, there may be considerable impact on agricultural land use due to snow melt, availability of irrigation, frequency and intensity of inter- and intra-seasonal droughts and floods, soil organic matter transformations, soil erosion, distribution and frequency of infestation by insect pests, diseases or weeds, the decline in arable areas (due to submergence of coastal lands), and availability of energy. An increase in atmospheric CO₂ promotes the growth and productivity of C3 plants. On the other hand, an increase in temperature, can reduce crop duration, increase crop respiration rates, affect the equilibrium between crops and pests, hasten nutrient mineralization in soils, decrease fertilizer- use efficiencies, and increase evapotranspiration among others. All these could considerably affect crop yield in long run. Climate resilient agriculture consisting of adaptation, mitigation, and other agriculture practices can potentially enhance the capacity of the system to withstand climate-related disturbances by resisting damage and recovering quickly. Climate resilient agriculture turns the climate change threats that have to be tackled into new business opportunities for the sector in different regions and therefore provides a triple win: mitigation, adaptation, and economic growth. Improving the soil organic carbon stock of soil is integral to any strategy towards adapting to and mitigating the abrupt climate change, advancing food security, and improving the environment. Soil carbon sequestration is one of the major mitigation strategies to achieve climate-resilient agriculture. Climate-smart agriculture is the only way to lower the negative impact of climate variations on crop adaptation before it might affect global crop production drastically. To cope with these extreme changes, future development needs to make adjustments in technology, management practices, and legislation. Adaptation and mitigation are twin approaches to bringing resilience to climate change in agriculture.

Keywords: climate change, global warming, crop production, climate resilient agriculture

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Authors: Pamela Chia, Tay Yoong Chuan

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Introduction: Severe pulmonary hypertension (PH) patients requiring non-cardiac surgery risk have increased mortality rates ranging. These patients are plagued with cardiorespiratory failure, dysrhythmias and anticoagulation potentially with concurrent sepsis and renal insufficiency, perioperative morbidity. We present a deaf-mute patient with severe idiopathic PH emergently prepared for ruptured ectopic laparotomy. Case Report: A 20 year-old female, 62kg (BMI 25 kg/m2) with severe idiopathic PH (2DE Ejection Fraction was 41%, Pulmonary Artery Systolic Pressure (PASP) 105 mmHg, Right ventricle strain and hypertrophy) and selective mutism was rushed in for emergency laparotomy after presenting to the emergency department for abdominal pain. The patient had an NYHA Class II with room air SpO2 93-95%. While awaiting lung transplant, the patient takes warfarin, Sildanefil, Macitentan and even Selexipag for rising PASP. At presentation, vital signs: BP 95/63, HR 119 SpO2 88% (room air). Despite decreasing haemoglobin 14 to 10g/dL, INR 2.59 was reversed with prothrombin concentrate, and Vitamin K. ECG revealed Right Bundle Branch Block with right ventricular strain and x-ray showed cardiomegaly, dilated Right Ventricle, Pulmonary Arteries, basal atelectasis. Arterial blood gas showed compensated metabolic acidosis pH 7.4 pCO2 32 pO2 53 HCO3 20 BE -4 SaO2 88%. The cardiothoracic surgeon concluded no role for Extracorporeal Membrane Oxygenation (ECMO). We inserted invasive arterial and central venous lines with blood transfusion via an 18G cannula before the patient underwent a midline laparotomy, haemostasis of ruptured ovarian cyst with 2.4L of clots under general anesthesia and FloTrac cardiac output monitoring. Rapid sequence induction was done with Midazolam/Propofol, remifentanil infusion, and rocuronium. The patient was maintained on Desflurane. Blood products and colloids were transfused for further 1.5L blood loss. Postoperatively, the patient was transferred to the intensive care unit and was extubated uneventfully 7hours later. The patient went home a week later. Discussion: Emergency hemostasis laparotomy in anticoagulated WHO Class I PH patient awaiting lung transplant with no ECMO backup poses tremendous stress on the deaf-mute patient and the anesthesiologist. Balancing hemodynamics avoiding hypotension while awaiting hemostasis in the presence of pulmonary arterial dilators and anticoagulation requires close titration of volatiles, which decreases RV contractility. We review the contraindicated anesthetic agents (ketamine, N2O), choice of vasopressors in hypotension to maintain Aortic-right ventricular pressure gradients and nitric oxide use perioperatively. Conclusion: Interdisciplinary communication with a deaf-mute moribund patient and anesthesia considerations pose many rare challenges worth sharing.

Keywords: pulmonary hypertension, case report, warfarin reversal, emergency surgery

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Authors: Angelos Evangelou, Katerina Loizou, Loukas Koutsokeras, Orestes Marangos, Giorgos Constantinides, Stylianos Yiatros, Katerina Sofocleous, Vasileios Drakonakis

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Owing to their outstanding strength to weight properties, carbon fiber reinforced polymer (CFRPs) composites have attracted significant attention finding use in various fields (sports, automotive, transportation, etc.). The current momentum indicates that there is an increasing demand for their employment in high value bespoke applications such as avionics and electronic casings, damage sensing structures, EMI (electromagnetic interference) structures that dictate the use of materials with increased electrical conductivity both in-plane and through the thickness. Several efforts by research groups have focused on enhancing the through-thickness electrical conductivity of FRPs, in an attempt to combine the intrinsically high relative strengths exhibited with improved z-axis electrical response as well. However, only a limited number of studies deal with printing of nano-enhanced polymer inks to produce a pattern on dry fabric level that could be used to fabricate CFRPs with improved through thickness electrical conductivity. The present study investigates the employment of screen-printing process on technical dry fabrics using nano-reinforced polymer-based inks to achieve the required through thickness conductivity, opening new pathways for the application of fiber reinforced composites in niche products. Commercially available inks and in-house prepared inks reinforced with electrically conductive nanoparticles are employed, printed in different patterns. The aim of the present study is to investigate both the effect of the nanoparticle concentration as well as the droplet patterns (diameter, inter-droplet distance and coverage) to optimize printing for the desired level of conductivity enhancement in the lamina level. The electrical conductivity is measured initially at ink level to pinpoint the optimum concentrations to be employed using a “four-probe” configuration. Upon printing of the different patterns, the coverage of the dry fabric area is assessed along with the permeability of the resulting dry fabrics, in alignment with the fabrication of CFRPs that requires adequate wetting by the epoxy matrix. Results demonstrated increased electrical conductivities of the printed droplets, with increase of the conductivity from the benchmark value of 0.1 S/M to between 8 and 10 S/m. Printability of dense and dispersed patterns has exhibited promising results in terms of increasing the z-axis conductivity without inhibiting the penetration of the epoxy matrix at the processing stage of fiber reinforced composites. The high value and niche prospect of the resulting applications that can stem from CFRPs with increased through thickness electrical conductivities highlights the potential of the presented endeavor, signifying screen printing as the process to to nano-enable z-axis electrical conductivity in composite laminas. This work was co-funded by the European Regional Development Fund and the Republic of Cyprus through the Research and Innovation Foundation (Project: ENTERPRISES/0618/0013).

Keywords: CFRPs, conductivity, nano-reinforcement, screen-printing

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Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

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Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

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Authors: Ankita Jadon, Sidi Souvi, Nathalie Girault, Denis Petitprez

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Safety requirements for Generation IV nuclear reactor designs, especially the new generation sodium-cooled fast reactors (SFR) require a risk-informed approach to model severe accidents (SA) and their consequences in case of outside release. In SFRs, aerosols are produced during a core disruptive accident when primary system sodium is ejected into the containment and burn in contact with the air; producing sodium aerosols. One of the key aspects of safety evaluation is the in-containment sodium aerosol behavior and their interaction with fission products. The study of the effects of sodium fires is essential for safety evaluation as the fire can both thermally damage the containment vessel and cause an overpressurization risk. Besides, during the fire, airborne fission product first dissolved in the primary sodium can be aerosolized or, as it can be the case for fission products, released under the gaseous form. The objective of this work is to study the interactions between sodium aerosols and fission products (Iodine, toxic and volatile, being the primary concern). Sodium fires resulting from an SA would produce aerosols consisting of sodium peroxides, hydroxides, carbonates, and bicarbonates. In addition to being toxic (in oxide form), this aerosol will then become radioactive. If such aerosols are leaked into the environment, they can pose a danger to the ecosystem. Depending on the chemical affinity of these chemical forms with fission products, the radiological consequences of an SA leading to containment leak tightness loss will also be affected. This work is split into two phases. Firstly, a method to theoretically understand the kinetics and thermodynamics of the heterogeneous reaction between sodium aerosols and fission products: I2 and HI are proposed. Ab-initio, density functional theory (DFT) calculations using Vienna ab-initio simulation package are carried out to develop an understanding of the surfaces of sodium carbonate (Na2CO3) aerosols and hence provide insight on its affinity towards iodine species. A comprehensive study of I2 and HI adsorption, as well as bicarbonate formation on the calculated lowest energy surface of Na2CO3, was performed which provided adsorption energies and description of the optimized configuration of adsorbate on the stable surface. Secondly, the heterogeneous reaction between (I2)g and Na2CO3 aerosols were investigated experimentally. To study this, (I2)g was generated by heating a permeation tube containing solid I2, and, passing it through a reaction chamber containing Na2CO3 aerosol deposit. The concentration of iodine was then measured at the exit of the reaction chamber. Preliminary observations indicate that there is an effective uptake of (I2)g on Na2CO3 surface, as suggested by our theoretical chemistry calculations. This work is the first step in addressing the gaps in knowledge of in-containment and atmospheric source term which are essential aspects of safety evaluation of SFR SA. In particular, this study is aimed to determine and characterize the radiological and chemical source term. These results will then provide useful insights for the developments of new models to be implemented in integrated computer simulation tool to analyze and evaluate SFR safety designs.

Keywords: iodine adsorption, sodium aerosols, sodium cooled reactor, DFT calculations, sodium carbonate

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Authors: Shah Rucksana Akhter Urme

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Agriculture is the main source of food for human consumption and feeding the world huge population, the pressure of food supply is increasing day by day. Undoubtedly, quality strain, improved plantation, farming technology, synthetic fertilizer, readily available irrigation, insecticides and harvesting technology are the main factors those to meet up the huge demand of food consumption all over the world. However, depended on this limited resources and excess amount of consuming lands, water, fertilizers leads to the end of the resources and severe climate effects has been left for our future generation. Agriculture is the most responsible to global warming, emitting more greenhouse gases than all other vehicles largely from nitrous oxide released by from fertilized fields, and carbon dioxide from the cutting of rain forests to grow crops . Farming is the thirstiest user of our precious water supplies and a major polluter, as runoff from fertilizers disrupts fragile lakes, rivers, and coastal ecosystems across the globe which accelerates the loss of biodiversity, crucial habitat and a major driver of wildlife extinction. It is needless to say that we have to more concern on how we can save the nutrients of the soil, storage of the water and avoid excessive depends on synthetic fertilizer and insecticides. In this case, eco- friendly cultivation could be a potential alternative solution to minimize effects of agriculture in our environment. The objective of this review paper is about organic cultivation following in particular biotechnological process focused on bio-fertilizer and bio-pesticides. Intense practice of chemical pesticides, insecticides has severe effect on both in human life and biodiversity. This cultivation process introduces farmer an alternative way which is nonhazardous, cost effective and ecofriendly. Organic fertilizer such as tea residue, ashes might be the best alternative to synthetic fertilizer those play important role in increasing soil nutrient and fertility. Ashes contain different essential and non-essential mineral contents that are required for plant growth. Organic pesticide such as neem spray is beneficial for crop as it is toxic for pest and insects. Recycled and composted crop wastes and animal manures, crop rotation, green manures and legumes etc. are suitable for soil fertility which is free from hazardous chemicals practice. Finally water hyacinth and algae are potential source of nutrients even alternative to soil for cultivation along with storage of water for continuous supply. Inorganic practice of agriculture, consuming fruits and vegetables becomes a threat for both human life and eco-system and synthetic fertilizer and pesticides are responsible for it. Farmers that practice eco-friendly farming have to implement steps to protect the environment, particularly by severely limiting the use of pesticides and avoiding the use of synthetic chemical fertilizers, which are necessary for organic systems to experience reduced environmental harm and health risk.

Keywords: organic farming, biopesticides, organic nutrients, water storage, global warming

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Authors: Grzegorz Raniszewski, Zbigniew Kolacinski, Lukasz Szymanski, Slawomir Wiak, Lukasz Pietrzak, Dariusz Koza

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One of the most promising area for carbon nanotubes (CNTs) application is medicine. One of the most devastating diseases is cancer. Carbon nanotubes may be used as carriers of a slowly released drug. It is possible to use of electromagnetic waves to destroy cancer cells by the carbon nanotubes (CNTs). In our research we focused on thermal ablation by ferromagnetic carbon nanotubes (Fe-CNTs). In the cancer cell hyperthermia functionalized carbon nanotubes are exposed to radio frequency electromagnetic field. Properly functionalized Fe-CNTs join the cancer cells. Heat generated in nanoparticles connected to nanotubes warm up nanotubes and then the target tissue. When the temperature in tumor tissue exceeds 316 K the necrosis of cancer cells may be observed. Several techniques can be used for Fe-CNTs synthesis. In our work, we use high-temperature methods where arc-discharge is applied. Low-temperature systems are microwave plasma with assisted chemical vapor deposition (MPCVD) and hybrid physical-chemical vapor deposition (HPCVD). In the arc discharge system, the plasma reactor works with a pressure of He up to 0,5 atm. The electric arc burns between two graphite rods. Vapors of carbon move from the anode, through a short arc column and forms CNTs which can be collected either from the reactor walls or cathode deposit. This method is suitable for the production of multi-wall and single-wall CNTs. A disadvantage of high-temperature methods is a low purification, short length, random size and multi-directional distribution. In MPCVD system plasma is generated in waveguide connected to the microwave generator. Then containing carbon and ferromagnetic elements plasma flux go to the quartz tube. The additional resistance heating can be applied to increase the reaction effectiveness and efficiency. CNTs nucleation occurs on the quartz tube walls. It is also possible to use substrates to improve carbon nanotubes growth. HPCVD system involves both chemical decomposition of carbon containing gases and vaporization of a solid or liquid source of catalyst. In this system, a tube furnace is applied. A mixture of working and carbon-containing gases go through the quartz tube placed inside the furnace. As a catalyst ferrocene vapors can be used. Fe-CNTs may be collected then either from the quartz tube walls or on the substrates. Low-temperature methods are characterized by higher purity product. Moreover, carbon nanotubes from tested CVD systems were partially filled with the iron. Regardless of the method of Fe-CNTs synthesis the final product always needs to be purified for applications in medicine. The simplest method of purification is an oxidation of the amorphous carbon. Carbon nanotubes dedicated for cancer cell thermal ablation need to be additionally treated by acids for defects amplification on the CNTs surface what facilitates biofunctionalization. Application of ferromagnetic nanotubes for cancer treatment is a promising method of fighting with cancer for the next decade. Acknowledgment: The research work has been financed from the budget of science as a research project No. PBS2/A5/31/2013

Keywords: arc discharge, cancer, carbon nanotubes, CVD, thermal ablation

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Authors: Noor S. Nasri, Eric C. A. Tatt, Usman D. Hamza, Jibril Mohammed, Husna M. Zain

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Climate change has becoming a global environmental issue that may trigger irreversible changes in the environment with catastrophic consequences for human, animals and plants on our planet. Methane, carbon dioxide and nitrous oxide are the greenhouse gases (GHG) and as the main factor that significantly contributes to the global warming. Mainly carbon dioxide be produced and released to atmosphere by thermal industrial and power generation sectors. Methane is dominant component of natural gas releases significant of thermal heat, and the gaseous pollutants when homogeneous thermal combustion takes place at high temperature. Heterogeneous catalytic Combustion (HCC) principle is promising technologies towards environmental friendly energy production should be developed to ensure higher yields with lower pollutants gaseous emissions and perform complete combustion oxidation at moderate temperature condition as comparing to homogeneous high thermal combustion. Hence the principle has become a very interesting alternative total oxidation for the treatment of pollutants gaseous emission especially NOX product formation. Noble metals are dispersed on a support-porous HCC such as γ- Al2O3, TiO2 and ThO2 to increase thermal stability of catalyst and to increase to effectiveness of catalytic combustion. Support-porous HCC material to be selected based on factors of the surface area, porosity, thermal stability, thermal conductivity, reactivity with reactants or products, chemical stability, catalytic activity, and catalyst life. γ- Al2O3 with high catalytic activity and can last longer life of catalyst, is commonly used as the support for Pd catalyst at low temperatures. Sustainable and renewable support-material of bio-mass char was derived from agro-industrial waste material and used to compare with those the conventional support-porous material. The abundant of biomass wastes generated in palm oil industries is one potential source to convert the wastes into sustainable material as replacement of support material for catalysts. Objective of this study was to compare the kinetic rate of reaction the combustion of methane on Palladium (Pd) based catalyst with Al2O3 support and bio-char (Bc) support derived from shell kernel. The 2wt% Pd was prepared using incipient wetness impregnation method and the HCC performance was accomplished using tubular quartz reactor with gas mixture ratio of 3% methane and 97% air. Material characterization was determined using TGA, SEM, and BET surface area. The methane porous-HCC conversion was carried out by online gas analyzer connected to the reactor that performed porous-HCC. BET surface area for prepared 2 wt% Pd/Bc is smaller than prepared 2wt% Pd/ Al2O3 due to its low porosity between particles. The order of catalyst activity based on kinetic rate on reaction of catalysts in low temperature is prepared 2wt% Pd/Bc > calcined 2wt% Pd/ Al2O3 > prepared 2wt% Pd/ Al2O3 > calcined 2wt% Pd/Bc. Hence the usage of agro-industrial bio-mass waste material can enhance the sustainability principle.

Keywords: catalytic-combustion, environmental, support-bio-char material, sustainable and renewable material

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Authors: Viktor D. Dubrovin, Masoud Mollaee, Jie Zong, Xiushan Zhu, Nasser Peyghambarian

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Glasses doped with high rare-earth (RE) elements concentration attracted considerable attention since the middle of the 20th century due to their particular magneto-optical properties. Such glasses exhibit the Faraday effect in which the polarization plane of a linearly polarized light beam is rotated by the interaction between the incident light and the magneto-optical material. That effect found application in optical isolators that are useful for laser systems, which can prevent back reflection of light into lasers or optical amplifiers and reduce signal instability and noise. Glasses are of particular interest since they are cost-effective and can be formed into fibers, thus breaking the limits of traditional bulk optics requiring optical coupling for use with fiber-optic systems. The advent of high-power fiber lasers operating near 2µm revealed a necessity in the development of all fiber isolators for this region. Ce³⁺, Pr³⁺, Dy³⁺, and Tb³⁺ ions provide the biggest contribution to the Verdet constant value of optical materials among the RE. It is known that Pr³⁺ and Tb³⁺ ions have strong absorption bands near 2 µm, thus making Dy³⁺ and Ce³⁺ the only prospective candidates for fiber isolator operating in that region. Due to the high tendency of Ce³⁺ ions pass to Ce⁴⁺ during the synthesis, glasses with high cerium content usually suffers from Ce⁴⁺ ions absorption extending from visible to IR. Additionally, Dy³⁺ (₆H¹⁵/²) same as Ho³⁺ (⁵I₈) ions, have the largest effective magnetic moment (µeff = 10.6 µB) among the RE ions that starts to play the key role if the operating region is far from 4fⁿ→ 4fⁿ⁻¹5 d¹ electric-dipole transition relevant to the Faraday Effect. Considering the high effective magnetic moment value of Er³⁺ ions (µeff = 9.6 µB) that is 3rd after Dy³⁺/ Ho³⁺ and Tb³⁺, it is possible to assume that Er³⁺ doped glasses should exhibit Verdet constant value near 2µm that is comparable with one of Dy doped glasses. Thus, partial replacement of Dy³⁺ on Er³⁺ ions has been performed, keeping the overall concentration of Re₂O₃ equal to 70 wt.% (30.6 mol.%). Al₂O₃-B₂O₃-SiO₂-30.6RE₂O₃ (RE= Er, Dy) glasses had been synthesized, and their thermal, spectral, optical, structural, and magneto-optical properties had been studied. Glasses synthesis had been conducted in Pt crucibles for 3h at 1500 °C. The obtained melt was poured into preheated up to 400 °C mold and annealed from 800 oC to room temperature for 12h with 1h dwell. The mass of obtained glass samples was about 200g. Shown that the difference between crystallization and glass transition temperature is about 150 oC, even taking into account the fact that high content of RE₂O₃ leads to glass network depolymerization. Verdet constant of Al₂O₃-B₂O₃-SiO₂-30.6RE₂O₃ glasses for wavelength 1950 nm can reach more than 5.9 rad/(T*m), which is among the highest number reported for a paramagnetic glass at this wavelength. The refractive index value was found to be equal to 1.7545 at 633 nm. Our experimental results show that Al₂O₃-B₂O₃-SiO₂-30.6RE₂O₃ glasses with high Dy₂O₃ content are expected to be promising material for use as highly effective Faraday isolators and modulators of electromagnetic radiation in the 2μm region.

Keywords: oxide glass, magneto-optical, dysprosium, erbium, Faraday rotator, boron-aluminosilicate system

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Authors: Maryam Hajrezaie, Mahmood Ameen Abdulla, Nazia Abdul Majid, Hapipa Mohd Ali, Pouya Hassandarvish, Maryam Zahedi Fard

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Background: Colon cancer is one of the most prevalent cancers in the world and is the third leading cause of death among cancers in both males and females. The incidence of colon cancer is ranked fourth among all cancers but varies in different parts of the world. Cancer chemoprevention is defined as the use of natural or synthetic compounds capable of inducing biological mechanisms necessary to preserve genomic fidelity. Andrographolide is the major labdane diterpenoidal constituent of the plant Andrographis paniculata (family Acanthaceae), used extensively in the traditional medicine. Extracts of the plant and their constituents are reported to exhibit a wide spectrum of biological activities of therapeutic importance. Laboratory animal model studies have provided evidence that Andrographolide play a role in inhibiting the risk of certain cancers. Objective: Our aim was to evaluate the chemopreventive efficacy of the Andrographolide in the AOM induced rat model. Methods: To evaluate inhibitory properties of andrographolide on colonic aberrant crypt foci (ACF), five groups of 7-week-old male rats were used. Group 1 (control group) were fed with 10% Tween 20 once a day, Group 2 (cancer control) rats were intra-peritoneally injected with 15 mg/kg Azoxymethan, Gropu 3 (drug control) rats were injected with 15 mg/kg azoxymethan and 5-Flourouracil, Group 4 and 5 (experimental groups) were fed with 10 and 20 mg/kg andrographolide each once a day. After 1 week, the treatment group rats received subcutaneous injections of azoxymethane, 15 mg/kg body weight, once weekly for 2 weeks. Control rats were continued on Tween 20 feeding once a day and experimental groups 10 and 20 mg/kg andrographolide feeding once a day for 8 weeks. All rats were sacrificed 8 weeks after the azoxymethane treatment. Colons were evaluated grossly and histopathologically for ACF. Results: Administration of 10 mg/kg and 20 mg/kg andrographolide were found to be effectively chemoprotective, as evidenced microscopily and biochemically. Andrographolide suppressed total colonic ACF formation up to 40% to 60%, respectively, when compared with control group. Pre-treatment with andrographolide, significantly reduced the impact of AOM toxicity on plasma protein and urea levels as well as on plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and gamma-glutamyl transpeptidase (GGT) activities. Grossly, colorectal specimens revealed that andrographolide treatments decreased the mean score of number of crypts in AOM-treated rats. Importantly, rats fed andrographolide showed 75% inhibition of foci containing four or more aberrant crypts. The results also showed a significant increase in glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO), and Prostaglandin E2 (PGE2) activities and a decrease in malondialdehyde (MDA) level. Histologically all treatment groups showed a significant decrease of dysplasia as compared to control group. Immunohistochemical staining showed up-regulation of Hsp70 and down-regulation of Bax proteins. Conclusion: The current study demonstrated that Andrographolide reduce the number of ACF. According to these data, Andrographolide might be a promising chemoprotective activity, in a model of AOM-induced in ACF.

Keywords: chemopreventive, andrographolide, colon cancer, aberrant crypt foci (ACF)

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Authors: T. N. Tran Thi, J. Morse, C. Detlefs, P. K. Cook, C. Yıldırım, A. C. Jakobsen, T. Zhou, J. Hartwig, V. Zurbig, D. Caliste, B. Fernandez, D. Eon, O. Loto, M. L. Hicks, A. Pakpour-Tabrizi, J. Baruchel

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The ability to grow boron-doped diamond epilayers of high crystalline quality is a prerequisite for the fabrication of diamond power electronic devices, in particular high voltage diodes and metal-oxide-semiconductor (MOS) transistors. Boron and intrinsic diamond layers are homoepitaxially overgrown by microwave assisted chemical vapour deposition (MWCVD) on single crystal high pressure, high temperature (HPHT) grown bulk diamond substrates. Various epilayer thicknesses were grown, with dopant concentrations ranging from 1021 atom/cm³ at nanometer thickness in the case of 'delta doping', up 1016 atom/cm³ and 50µm thickness or high electric field drift regions. The crystalline quality of these overgrown layers as regards defects, strain, distortion… is critical for the device performance through its relation to the final electrical properties (Hall mobility, breakdown voltage...). In addition to the optimization of the epilayer growth conditions in the MWCVD reactor, other important questions related to the crystalline quality of the overgrown layer(s) are: 1) what is the dependence on the bulk quality and surface preparation methods of the HPHT diamond substrate? 2) how do defects already present in the substrate crystal propagate into the overgrown layer; 3) what types of new defects are created during overgrowth, what are their growth mechanisms, and how can these defects be avoided? 4) how can we relate in a quantitative manner parameters related to the measured crystalline quality of the boron doped layer to the electronic properties of final processed devices? We describe synchrotron-based techniques developed to address these questions. These techniques allow the visualization of local defects and crystal distortion which complements the data obtained by other well-established analysis methods such as AFM, SIMS, Hall conductivity…. We have used Grazing Incidence X-ray Diffraction (GIXRD) at the ID01 beamline of the ESRF to study lattice parameters and damage (strain, tilt and mosaic spread) both in diamond substrate near surface layers and in thick (10–50 µm) overgrown boron doped diamond epi-layers. Micro- and nano-section topography have been carried out at both the BM05 and ID06-ESRF) beamlines using rocking curve imaging techniques to study defects which have propagated from the substrate into the overgrown layer(s) and their influence on final electronic device performance. These studies were performed using various commercially sourced HPHT grown diamond substrates, with the MWCVD overgrowth carried out at the Fraunhofer IAF-Germany. The synchrotron results are in good agreement with low-temperature (5°K) cathodoluminescence spectroscopy carried out on the grown samples using an Inspect F5O FESEM fitted with an IHR spectrometer.

Keywords: synchrotron X-ray diffaction, crystalline quality, defects, diamond overgrowth, rocking curve imaging

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Authors: Asmat Nawaz, Ceylan Zafer, Ali K. Erdinc, Kaiying Wang, M. Nadeem Akram

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Hybrid halide Perovskites with the general formula ABX₃, where X = Cl, Br or I, are considered as an ideal candidates for the preparation of photovoltaic devices. The most commonly and successfully used hybrid halide perovskite for photovoltaic applications is CH₃NH₃PbI₃ and its analogue prepared from lead chloride, commonly symbolized as CH₃NH₃PbI₃_ₓClₓ. Some researcher groups are using lead free (Sn replaces Pb) and mixed halide perovskites for the fabrication of the devices. Both mesoporous and planar structures have been developed. By Comparing mesoporous structure in which the perovskite materials infiltrate into mesoporous metal oxide scaffold, the planar architecture is much simpler and easy for device fabrication. In a typical perovskite solar cell, a perovskite absorber layer is sandwiched between the hole and electron transport. Upon the irradiation, carriers are created in the absorber layer that can travel through hole and electron transport layers and the interface in between. We fabricated inverted planar heterojunction structure ITO/PEDOT/ Perovskite/PCBM/Al, based solar cell via two-step spin coating method. This is also called Sequential deposition method. A small amount of cheap additive H₂O was added into PbI₂/DMF to make a homogeneous solution. We prepared four different solution such as (W/O H₂O, 1% H₂O, 2% H₂O, 3% H₂O). After preparing, the whole night stirring at 60℃ is essential for the homogenous precursor solutions. We observed that the solution with 1% H₂O was much more homogenous at room temperature as compared to others. The solution with 3% H₂O was precipitated at once at room temperature. The four different films of PbI₂ were formed on PEDOT substrates by spin coating and after that immediately (before drying the PbI₂) the substrates were immersed in the methyl ammonium iodide solution (prepared in isopropanol) for the completion of the desired perovskite film. After getting desired films, rinse the substrates with isopropanol to remove the excess amount of methyl ammonium iodide and finally dried it on hot plate only for 1-2 minutes. In this study, we added H₂O in the PbI₂/DMF precursor solution. The concept of additive is widely used in the bulk- heterojunction solar cells to manipulate the surface morphology, leading to the enhancement of the photovoltaic performance. There are two most important parameters for the selection of additives. (a) Higher boiling point w.r.t host material (b) good interaction with the precursor materials. We observed that the morphology of the films was improved and we achieved a denser, uniform with less cavities and almost full surface coverage films but only using precursor solution having 1% H₂O. Therefore, we fabricated the complete perovskite solar cell by sequential deposition technique with precursor solution having 1% H₂O. We concluded that with the addition of additives in the precursor solutions one can easily be manipulate the morphology of the perovskite film. In the sequential deposition method, thickness of perovskite film is in µm and the charge diffusion length of PbI₂ is in nm. Therefore, by controlling the thickness using other deposition methods for the fabrication of solar cells, we can achieve the better efficiency.

Keywords: methylammonium lead iodide, perovskite solar cell, precursor composition, sequential deposition

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Authors: Alex B. Cusick

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The objective of this study is to improve upon the current ²³⁸PuO₂ fuel technology for space and defense applications. Modern RTGs (radioisotope thermoelectric generators) utilize the heat generated from the radioactive decay of ²³⁸Pu to create heat and electricity for long term and remote missions. Application of RTG technology is limited by the scarcity and expense of producing the isotope, as well as the power output which is limited to only a few hundred watts. The scarcity and expense make the efficient use of ²³⁸Pu absolutely necessary. By utilizing the decay of ²³⁸Pu, not only to produce heat directly but to also indirectly induce fission in ²³⁹Pu (which is already present within currently used fuel), it is possible to see large increases in temperature which allows for a more efficient conversion to electricity and a higher power-to-weight ratio. This concept can reduce the quantity of ²³⁸Pu necessary for these missions, potentially saving millions on investment, while yielding higher power output. Current work investigating radioisotope power systems have focused on improving efficiency of the thermoelectric components and replacing systems which produce heat by virtue of natural decay with fission reactors. The technical feasibility of utilizing (α,n) reactions to induce fission within current radioisotopic fuels has not been investigated in any appreciable detail, and our study aims to thoroughly investigate the performance of many such designs, develop those with highest capabilities, and facilitate experimental testing of these designs. In order to determine the specific design parameters that maximize power output and the efficient use of ²³⁸Pu for future RTG units, MCNP6 simulations have been used to characterize the effects of modifying fuel composition, geometry, and porosity, as well as introducing neutron moderating, reflecting, and shielding materials to the system. Although this project is currently in the preliminary stages, the final deliverables will include sophisticated designs and simulation models that define all characteristics of multiple novel RTG fuels, detailed enough to allow immediate fabrication and testing. Preliminary work has consisted of developing a benchmark model to accurately represent the ²³⁸PuO₂ pellets currently in use by NASA; this model utilizes the alpha transport capabilities of MCNP6 and agrees well with experimental data. In addition, several models have been developed by varying specific parameters to investigate their effect on (α,n) and (n,fi ssion) reaction rates. Current practices in fuel processing are to exchange out the small portion of naturally occurring ¹⁸O and ¹⁷O to limit (α,n) reactions and avoid unnecessary neutron production. However, we have shown that enriching the oxide in ¹⁸O introduces a sufficient (α,n) reaction rate to support significant fission rates. For example, subcritical fission rates above 10⁸ f/cm³-s are easily achievable in cylindrical ²³⁸PuO₂ fuel pellets with a ¹⁸O enrichment of 100%, given an increase in size and a ⁹Be clad. Many viable designs exist and our intent is to discuss current results and future endeavors on this project.

Keywords: radioisotope thermoelectric generators (RTG), Pu-238, subcritical reactors, (alpha, n) reactions

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Authors: Renata Gerhardt, Detlev Belder

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Raman spectroscopy has attracted much attention as a structurally descriptive and label-free detection method. It is particularly suited for chemical analysis given as it is non-destructive and molecules can be identified via the fingerprint region of the spectra. In this work possibilities are investigated how to integrate Raman spectroscopy as a detection method for chip-based chromatography, making use of a droplet interface. A demanding task in lab-on-a-chip applications is the specific and sensitive detection of low concentrated analytes in small volumes. Fluorescence detection is frequently utilized but restricted to fluorescent molecules. Furthermore, no structural information is provided. Another often applied technique is mass spectrometry which enables the identification of molecules based on their mass to charge ratio. Additionally, the obtained fragmentation pattern gives insight into the chemical structure. However, it is only applicable as an end-of-the-line detection because analytes are destroyed during measurements. In contrast to mass spectrometry, Raman spectroscopy can be applied on-chip and substances can be processed further downstream after detection. A major drawback of Raman spectroscopy is the inherent weakness of the Raman signal, which is due to the small cross-sections associated with the scattering process. Enhancement techniques, such as surface enhanced Raman spectroscopy (SERS), are employed to overcome the poor sensitivity even allowing detection on a single molecule level. In SERS measurements, Raman signal intensity is improved by several orders of magnitude if the analyte is in close proximity to nanostructured metal surfaces or nanoparticles. The main gain of lab-on-a-chip technology is the building block-like ability to seamlessly integrate different functionalities, such as synthesis, separation, derivatization and detection on a single device. We intend to utilize this powerful toolbox to realize Raman detection in chip-based chromatography. By interfacing on-chip separations with a droplet generator, the separated analytes are encapsulated into numerous discrete containers. These droplets can then be injected with a silver nanoparticle solution and investigated via Raman spectroscopy. Droplet microfluidics is a sub-discipline of microfluidics which instead of a continuous flow operates with the segmented flow. Segmented flow is created by merging two immiscible phases (usually an aqueous phase and oil) thus forming small discrete volumes of one phase in the carrier phase. The study surveys different chip designs to realize coupling of chip-based chromatography with droplet microfluidics. With regards to maintaining a sufficient flow rate for chromatographic separation and ensuring stable eluent flow over the column different flow rates of eluent and oil phase are tested. Furthermore, the detection of analytes in droplets with surface enhanced Raman spectroscopy is examined. The compartmentalization of separated compounds preserves the analytical resolution since the continuous phase restricts dispersion between the droplets. The droplets are ideal vessels for the insertion of silver colloids thus making use of the surface enhancement effect and improving the sensitivity of the detection. The long-term goal of this work is the first realization of coupling chip based chromatography with droplets microfluidics to employ surface enhanced Raman spectroscopy as means of detection.

Keywords: chip-based separation, chip LC, droplets, Raman spectroscopy, SERS

Procedia PDF Downloads 245

Authors: komal verma, V. S. Moholkar

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In this current study, the challenge of effectively treating and mineralizing industrial wastewater prior to its discharge into natural water bodies, such as rivers and lakes, is being addressed. Particularly, the focus is on the wastewater produced by chemical process industries, including refineries, petrochemicals, fertilizer, pharmaceuticals, pesticides, and dyestuff industries. These wastewaters often contain stubborn organic pollutants that conventional techniques, such as microbial processes cannot efficiently degrade. To tackle this issue, a ternary hybrid technique comprising of adsorption, heterogeneous Fenton process, and sonication has been employed. The study aims to evaluate the effectiveness of this approach for treating and mineralizing wastewater from a fertilizer industry located in Northeast India. The study comprises several key components, starting with the synthesis of the Fe3O4@AC nanocomposite using the co-precipitation method. The nanocomposite is then subjected to comprehensive characterization through various standard techniques, including FTIR, FE-SEM, EDX, TEM, BET surface area analysis, XRD, and magnetic property determination using VSM. Next, the process parameters of wastewater treatment are statistically optimized, focusing on achieving a high level of COD (Chemical Oxygen Demand) removal as the response variable. The Fe3O4@AC nanocomposite's adsorption characteristics and kinetics are also assessed in detail. The remarkable outcome of this study is the successful application of the ternary hybrid technique, combining adsorption, Fenton process, and sonication. This approach proves highly effective, leading to nearly complete mineralization (or TOC removal) of the fertilizer industry wastewater. The results highlight the potential of the Fe3O4@AC nanocomposite and the ternary hybrid technique as a promising solution for tackling challenging wastewater pollutants from various chemical process industries. This paper reports investigations in the mineralization of industrial wastewater (COD = 3246 mg/L, TOC = 2500 mg/L) using a ternary (ultrasound + Fenton + adsorption) hybrid advanced oxidation process. Fe3O4 decorated activated charcoal (Fe3O4@AC) nanocomposites (surface area = 538.88 m2/g; adsorption capacity = 294.31 mg/g) were synthesized using co-precipitation. The wastewater treatment process was optimized using central composite statistical design. At optimum conditions, viz. pH = 4.2, H2O2 loading = 0.71 M, adsorbent dose = 0.34 g/L, reduction in COD and TOC of wastewater were 94.75% and 89%, respectively. This result results from synergistic interactions among the adsorption of pollutants onto activated charcoal and surface Fenton reactions induced due to the leaching of Fe2+/Fe3+ ions from the Fe3O4 nanoparticles. Micro-convection generated due to sonication assisted faster mass transport (adsorption/desorption) of pollutants between Fe3O4@AC nanocomposite and the solution. The net result of this synergism was high interactions and reactions among and radicals and pollutants that resulted in the effective mineralization of wastewater. The Fe3O4@AC showed excellent recovery (> 90 wt%) and reusability (> 90% COD removal) in 5 successive cycles of treatment. LC-MS analysis revealed effective (> 50%) degradation of more than 25 significant contaminants (in the form of herbicides and pesticides) after the treatment with ternary hybrid AOP. Similarly, the toxicity analysis test using the seed germination technique revealed ~ 60% reduction in the toxicity of the wastewater after treatment.

Keywords: chemical oxygen demand (cod), fe3o4@ac nanocomposite, kinetics, lc-ms, rsm, toxicity

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Authors: Nikolaus Wilke, Boaz Paz

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Museum staff, conservators, restorers, curators, registrars, art handlers but potentially also museum visitors are often exposed to the harmful effects of biocides, which have been applied to collections in the past for the protection and preservation of cultural heritage. Due to stable light, moisture, and temperature conditions, the biocidal active ingredients were preserved for much longer than originally assumed by chemists, pest controllers, and museum scientists. Given the requirements to minimize the use and handling of toxic substances and the obligations of employers regarding safe working environments for their employees, but also for visitors, the museum sector worldwide needs adequate decontamination solutions. Today there are millions of contaminated objects in museums. This paper introduces the results of a systematic investigation into the reduction rate of biocide contamination in various organic materials that were treated with the humidity and temperature controlled ICM (Integrated Contamination Management) method. In the past, collections were treated with a wide range, at times even with a combination of toxins, either preventively or to eliminate active insect or fungi infestations. It was only later that most of those toxins were recognized as CMR (cancerogenic mutagen reprotoxic) substances. Among them were numerous chemical substances that are banned today because of their toxicity. While the biocidal effect of inorganic salts such as arsenic (arsenic(III) oxide), sublimate (mercury(II) chloride), copper oxychloride (basic copper chloride) and zinc chloride was known very early on, organic tar distillates such as paradichlorobenzene, carbolineum, creosote and naphthalene were increasingly used from the 19th century onwards, especially as wood preservatives. With the rapid development of organic synthesis chemistry in the 20th century and the development of highly effective warfare agents, pesticides and fungicides, these substances were replaced by chlorogenic compounds (e.g. γ-hexachlorocyclohexane (lindane), dichlorodiphenyltrichloroethane (DDT), pentachlorophenol (PCP), hormone-like derivatives such as synthetic pyrethroids (e.g., permethrin, deltamethrin, cyfluthrin) and phosphoric acid esters (e.g., dichlorvos, chlorpyrifos). Today we know that textile artifacts (costumes, uniforms, carpets, tapestries), wooden objects, herbaria, libraries, archives and historical wall decorations made of fabric, paper and leather were also widely treated with toxic inorganic and organic substances. The migration (emission) of pollutants from the contaminated objects leads to continuous (secondary) contamination and accumulation in the indoor air and dust. It is important to note that many of mentioned toxic substances are also material-damaging; they cause discoloration and corrosion. Some, such as DDT, form crystals, which in turn can cause micro tectonic, destructive shifting, for example, in paint layers. Museums must integrate sustainable solutions to address the residual biocide problems already in the planning phase. Gas and dust phase measurements and analysis must become standard as well as methods of decontamination.

Keywords: biocides, decontamination, museum collections, toxic substances in museums

Procedia PDF Downloads 114

Authors: M. Balordi, G. Santucci de Magistris, F. Pini, P. Marcacci

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The increasing of extreme meteorological events represents the most important causes of damages and blackouts of the whole electric system. In particular, the icing on ground-wires and overheads lines, due to snowstorms or harsh winter conditions, very often gives rise to the collapse of cables and towers both in cold and warm climates. On the other hand, the high concentration of contaminants in the air, due to natural and/or antropic causes, is reflected in high levels of pollutants layered on glass and ceramic insulators, causing frequent and unpredictable flashover events. Overheads line and insulator failures lead to blackouts, dangerous and expensive maintenances and serious inefficiencies in the distribution service. Inducing superhydrophobic (SHP) properties to conductors, ground-wires and insulators, is one of the ways to face all these problems. Indeed, in some cases, the SHP surface can delay the ice nucleation time and decrease the ice nucleation temperature, preventing ice formation. Besides, thanks to the low surface energy, the adhesion force between ice and a superhydrophobic material are low and the ice can be easily detached from the surface. Moreover, it is well known that superhydrophobic surfaces can have self-cleaning properties: these hinder the deposition of pollution and decrease the probability of flashover phenomena. Here this study presents three different studies to impart superhydrophobicity to aluminum, zinc and glass specimens, which represent the main constituent materials of conductors, ground-wires and insulators, respectively. The route to impart the superhydrophobicity to the metallic surfaces can be summarized in a three-step process: 1) sandblasting treatment, 2) chemical-hydrothermal treatment and 3) coating deposition. The first step is required to create a micro-roughness. In the chemical-hydrothermal treatment a nano-scale metallic oxide (Al or Zn) is grown and, together with the sandblasting treatment, bring about a hierarchical micro-nano structure. By coating an alchilated or fluorinated siloxane coating, the surface energy decreases and gives rise to superhydrophobic surfaces. In order to functionalize the glass, different superhydrophobic powders, obtained by a sol-gel synthesis, were prepared. Further, the specimens were covered with a commercial primer and the powders were deposed on them. All the resulting metallic and glass surfaces showed a noticeable superhydrophobic behavior with a very high water contact angles (>150°) and a very low roll-off angles (<5°). The three optimized processes are fast, cheap and safe, and can be easily replicated on industrial scales. The anti-icing and self-cleaning properties of the surfaces were assessed with several indoor lab-tests that evidenced remarkable anti-icing properties and self-cleaning behavior with respect to the bare materials. Finally, to evaluate the anti-snow properties of the samples, some SHP specimens were exposed under real snow-fall events in the RSE outdoor test-facility located in Vinadio, western Alps: the coated samples delay the formation of the snow-sleeves and facilitate the detachment of the snow. The good results for both indoor and outdoor tests make these materials promising for further development in large scale applications.

Keywords: superhydrophobic coatings, anti-icing, self-cleaning, anti-snow, overheads lines

Procedia PDF Downloads 183

Authors: Zuzana Tatarkova, Ivana Pilchova, Michal Cibulka, Martin Kolisek, Peter Racay, Peter Kaplan

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Introduction: Normal functioning of mitochondria is crucial for cardiac performance. Mitochondria undergo mitophagy and biogenesis, and mitochondrial proteins are subject to extensive post-translational modifications. The state of mitochondrial homeostasis reflects overall cellular fitness and longevity. Perturbed mitochondria produce less ATP, release greater amounts of reactive molecules, and are more prone to apoptosis. Therefore mitochondrial turnover is an integral aspect of quality control in which dysfunctional mitochondria are selectively eliminated through mitophagy. Currently, the progressive deterioration of physiological functions is seen as accumulation of modified/damaged proteins with limiting regenerative ability and disturbance of such affected protein-protein communication throughout aging in myocardial cells. Methodologies: For our study was used immunohistochemistry, biochemical methods: spectrophotometry, western blotting, immunodetection as well as more sophisticated 2D electrophoresis and mass spectrometry for evaluation protein-protein interactions and specific post-translational modification. Results and Discussion: Mitochondrial stress response to reactive species was evaluated as electron transport chain (ETC) complexes, redox-active molecules, and their possible communication. Protein-protein interactions revealed a strong linkage between age and ETC protein subunits. Redox state was strongly affected in senescent mitochondria with shift in favor of more pro-oxidizing condition within cardiomyocytes. Acute myocardial ischemia and ischemia-reperfusion (IR) injury affected ETC complexes I, II and IV with no change in complex III. Ischemia induced decrease in total antioxidant capacity, MnSOD, GSH and catalase activity with recovery in some extent during reperfusion. While MnSOD protein content was higher in IR group, activity returned to 95% of control. Nitric oxide is one of the biological molecules that can out compete MnSOD for superoxide and produce peroxynitrite. This process is faster than dismutation and led to the 10-fold higher production of nitrotyrosine after IR injury in adult with higher protection in senescent ones. 2D protein profiling revealed 140 mitochondrial proteins, 12 of them with significant changes after IR injury and 36 individual nitrotyrosine-modified proteins further identified by mass spectrometry. Linking these two groups, 5 proteins were altered after IR as well as nitrated, but only one showed massive nitration per lowering content of protein after IR injury in adult. Conclusions: Senescent cells have greater proportion of protein content, which might be modulated by several post-translational modifications. If these protein modifications are connected to functional consequences and protein-protein interactions are revealed, link may lead to the solution. Assume all together, dysfunctional proteostasis can play a causative role and restoration of protein homeostasis machinery is protective against aging and possibly age-related disorders. This work was supported by the project VEGA 1/0018/18 and by project 'Competence Center for Research and Development in the field of Diagnostics and Therapy of Oncological diseases', ITMS: 26220220153, co-financed from EU sources.

Keywords: aging heart, mitochondria, proteomics, redox state

Procedia PDF Downloads 167

Authors: Şeyma Dombaycıoğlu, Hilal Köse, Ali Osman Aydın, Hatem Akbulut

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Rechargeable lithium ion batteries (LIBs) have been considered as one of the most attractive energy storage choices for laptop computers, electric vehicles and cellular phones owing to their high energy and power density. Compared with conventional carbonaceous materials, transition metal oxides (TMOs) have attracted great interests and stand out among versatile novel anode materials due to their high theoretical specific capacity, wide availability and good safety performance. ZnO, as an anode material for LIBs, has a high theoretical capacity of 978 mAh g-1, much higher than that of the conventional graphite anode (∼370 mAhg-1). However, several major problems such as poor cycleability, resulting from the severe volume expansion and contraction during the alloying-dealloying cycles with Li+ ions and the associated charge transfer process, the pulverization and the agglomeration of individual particles, which drastically reduces the total entrance/exit sites available for Li+ ions still hinder the practical use of ZnO powders as an anode material for LIBs. Therefore, a great deal of effort has been devoted to overcome these problems, and many methods have been developed. In most of these methods, it is claimed that carbon nanotubes (CNTs) will radically improve the performance of batteries, because their unique structure may especially enhance the kinetic properties of the electrodes and result in an extremely high specific charge compared with the theoretical limits of graphitic carbon. Due to outstanding properties of CNTs, MWCNT buckypaper substrate is considered a buffer material to prevent mechanical disintegration of anode material during the battery applications. As the bridge connecting the positive and negative electrodes, the electrolyte plays a critical role affecting the overall electrochemical performance of the cell including rate, capacity, durability and safety. Commercial electrolytes for Li-ion batteries normally consist of certain lithium salts and mixed organic linear and cyclic carbonate solvents. Most commonly, LiPF6 is attributed to its remarkable features including high solubility, good ionic conductivity, high dissociation constant and satisfactory electrochemical stability for commercial fabrication. Besides LiPF6, LiBF4 is well known as a conducting salt for LIBs. LiBF4 shows a better temperature stability in organic carbonate based solutions and less moisture sensitivity compared to LiPF6. In this work, free standing zinc oxide (ZnO) and multiwalled carbon nanotube (MWCNT) nanocomposite materials were prepared by a sol gel technique giving a high capacity anode material for lithium ion batteries. Electrolyte solutions (including 1 m Li+ ion) were prepared with different Li salts in glove box. For this purpose, LiPF6 and LiBF4 salts and also mixed of these salts were solved in EC:DMC solvents (1:1, w/w). CR2016 cells were assembled by using these prepared electrolyte solutions, the ZnO/MWCNT buckypaper nanocomposites as working electrodes, metallic lithium as cathode and polypropylene (PP) as separator. For investigating the effect of different Li salts on the electrochemical performance of ZnO/MWCNT nanocomposite anode material electrochemical tests were performed at room temperature.

Keywords: anode, electrolyte, Li-ion battery, ZnO/MWCNT

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Authors: Miguel A. Figueroa, José A. Lara-Ramos, Miguel A. Mueses

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Pharmaceutical residues are a section of emerging contaminants of anthropogenic origin that are present in a myriad of waters with which human beings interact daily and are starting to affect the ecosystem directly. Conventional waste-water treatment systems are not capable of degrading these pharmaceutical effluents because their designs cannot handle the intermediate products and biological effects occurring during its treatment. That is why it is necessary to hybridize conventional waste-water systems with non-conventional processes. In the specific case of an ozonation process, its efficiency highly depends on a perfect dispersion of ozone, long times of interaction of the gas-liquid phases and the size of the ozone bubbles formed through-out the reaction system. In order to increase the efficiency of these parameters, the use of a modified flotation cell has been proposed recently as a reactive system, which is used at an industrial level to facilitate the suspension of particles and spreading gas bubbles through the reactor volume at a high rate. The objective of the present work is the development of a mathematical model that can closely predict the kinetic rates of reactions taking place in the flotation cell at an experimental scale by means of identifying proper reaction mechanisms that take into account the modified chemical and hydrodynamic factors in the FeO-catalyzed Ozonation of Diclofenac aqueous solutions in a flotation cell. The methodology is comprised of three steps: an experimental phase where a modified flotation cell reactor is used to analyze the effects of ozone concentration and loading catalyst over the degradation of Diclofenac aqueous solutions. The performance is evaluated through an index of utilized ozone, which relates the amount of ozone supplied to the system per milligram of degraded pollutant. Next, a theoretical phase where the reaction mechanisms taking place during the experiments must be identified and proposed that details the multiple direct and indirect reactions the system goes through. Finally, a kinetic model is obtained that can mathematically represent the reaction mechanisms with adjustable parameters that can be fitted to the experimental results and give the model a proper physical meaning. The expected results are a robust reaction rate law that can simulate the improved results of Diclofenac mineralization on water using the modified flotation cell reactor. By means of this methodology, the following results were obtained: A robust reaction pathways mechanism showcasing the intermediates, free-radicals and products of the reaction, Optimal values of reaction rate constants that simulated Hatta numbers lower than 3 for the system modeled, degradation percentages of 100%, TOC (Total organic carbon) removal percentage of 69.9 only requiring an optimal value of FeO catalyst of 0.3 g/L. These results showed that a flotation cell could be used as a reactor in ozonation, catalytic ozonation and photocatalytic ozonation processes, since it produces high reaction rate constants and reduces mass transfer limitations (Ha > 3) by producing microbubbles and maintaining a good catalyst distribution.

Keywords: advanced oxidation technologies, iron oxide, emergent contaminants, AOTS intensification

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Authors: Mohammed S. Razali, Kamel Khimeche, Dahah Hichem, Ammar Boudjellal, Djamel E. Kaderi, Nourddine Ramdani

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The use of additive manufacturing technologies has revolutionized various aspects of our daily lives. In particular, 3D printing has greatly advanced biomedical applications. While fused filament fabrication (FFF) technologies have made it easy to produce or prototype various medical devices, it is crucial to minimize the risk of contamination. New materials with antibacterial properties, such as those containing compounded silver nanoparticles, have emerged on the market. In a previous study, we prepared a newly sintered seashell filler (SSh) from bio-based seashells found along the Mediterranean coast using a suitable heat treatment process. We then prepared a series of polylactic acid (PLA) and polybutylene succinate (PBS) biocomposites filled with these SSh particles using a melt mixing technique with a twin-screw extruder to use them as feedstock filaments for 3D printing. The study consisted of two parts: evaluating the antibacterial activity of newly prepared biocomposites made of PLA and PBS reinforced with a sintered seashell in the first part and experimental and modeling analysis of the non-isothermal crystallization kinetics of these biocomposites in the second part. In the first part, the bactericidal activity of the biocomposites against three different bacteria, including Gram-negative bacteria such as (E. coli and Pseudomonas aeruginosa), as well as Gram-positive bacteria such as (Staphylococcus aureus), was examined. The PLA-based biocomposite containing 20 wt.% of SSh particles exhibited an inhibition zone with radial diameters of 8mm and 6mm against E. coli and Pseudo. Au, respectively, while no bacterial activity was observed against Staphylococcus aureus. In the second part, the focus was on investigating the effect of the sintered seashell filler particles on the non-isothermal crystallization kinetics of PLA and PBS 3D-printing composite materials. The objective was to understand the impact of the filler particles on the crystallization mechanism of both PLA and PBS during the cooling process of a melt-extruded filament in (FFF) to manage the dimensional accuracy and mechanical properties of the final printed part. We conducted a non-isothermal melt crystallization kinetic study of a series of PLA-SS and PBS-SS composites using differential scanning calorimetry at various cooling rates. We analyzed the obtained kinetic data using different crystallization kinetic models such as modified Avrami, Ozawa, and Mo's methods. Dynamic mode describes the relative crystallinity as a function of temperature; it found that time half crystallinity (t1/2) of neat PLA decreased from 17 min to 7.3 min for PLA+5 SSh and the (t1/2) of virgin PBS was reduced from 3.5 min to 2.8 min for the composite containing 5wt.% of SSh. We found that the coated SS particles with stearic acid acted as nucleating agents and had a nucleation activity, as observed through polarized optical microscopy. Moreover, we evaluated the effective energy barrier of the non-isothermal crystallization process using the Iso conversional methods of Flynn-Wall-Ozawa (F-W-O) and Kissinger-Akahira-Sunose (K-A-S). The study provides significant insights into the crystallization behavior of PLA and PBS biocomposites.

Keywords: avrami model, bio-based reinforcement, dsc, gram-negative bacteria, gram-positive bacteria, isoconversional methods, non-isothermal crystallization kinetics, poly(butylene succinate), poly(lactic acid), antbactirial activity

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Authors: Rabindranath Bag, Surjeet Singh

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Materials in which the electrons are strongly correlated provide some of the most challenging and exciting problems in condensed matter physics today. After the discovery of high critical temperature superconductivity in layered or two-dimensional copper oxides, many physicists got attention in cuprates and it led to an upsurge of interest in the synthesis and physical properties of copper-oxide based material. The quest to understand superconducting mechanism in high-temperature cuprates, drew physicist’s attention to somewhat simpler compounds consisting of spin-chains or one-dimensional lattice of coupled spins. Low-dimensional quantum magnets are of huge contemporary interest in basic sciences as well emerging technologies such as quantum computing and quantum information theory, and heat management in microelectronic devices. Spin ladder is an example of quasi one-dimensional quantum magnets which provides a bridge between one and two dimensional materials. One of the examples of quasi one-dimensional spin-ladder compounds is Sr14Cu24O41, which exhibits a lot of interesting and exciting physical phenomena in low dimensional systems. Very recently, the ladder compound Sr14Cu24O41 was shown to exhibit long-distance quantum entanglement crucial to quantum information theory. Also, it is well known that hole-compensation in this material results in very high (metal-like) anisotropic thermal conductivity at room temperature. These observations suggest that Sr14Cu24O41 is a potential multifunctional material which invites further detailed investigations. To investigate these properties one must needs a large and high quality of single crystal. But these systems are showing incongruently melting behavior, which brings many difficulties to grow a large and quality of single crystals. Hence, we are using TSFZ (Travelling Solvent Floating Zone) method to grow the high quality of single crystals of the low dimensional magnets. Apart from this, it has unique crystal structure (alternating stacks of plane containing edge-sharing CuO2 chains, and the plane containing two-leg Cu2O3 ladder with intermediate Sr layers along the b- axis), which is also incommensurate in nature. It exhibits abundant physical phenomenon such as spin dimerization, crystallization of charge holes and charge density wave. The maximum focus of research so far involved in introducing defects on A-site (Sr). However, apart from the A-site (Sr) doping, there are only few studies in which the B-site (Cu) doping of polycrystalline Sr14Cu24O41 have been discussed and the reason behind this is the possibility of two doping sites for Cu (CuO2 chain and Cu2O3 ladder). Therefore, in our present work, the crystals (pristine and Cu-site doped) were grown by using TSFZ method by tuning the growth parameters. The Laue diffraction images, optical polarized microscopy and Scanning Electron Microscopy (SEM) images confirm the quality of the grown crystals. Here, we report the single crystal growth, magnetic and transport properties of Sr14Cu24O41 and its lightly doped variants (magnetic and non-magnetic) containing less than 1% of Co, Ni, Al and Zn impurities. Since, any real system will have some amount of weak disorder, our studies on these ladder compounds with controlled dilute disorder would be significant in the present context.

Keywords: low-dimensional quantum magnets, single crystal, spin-ladder, TSFZ technique

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Authors: Avdhesh K. Sharma

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Key, in the development of energy-efficient micro-scale heat exchanger devices, is to select large heat transfer surface to volume ratio without much expanse on re-circulated pumps. The increased interest in short heat exchanger (SHE) is due to accessibility of advanced technologies for manufacturing of micro-tubes in range of 1 micron m - 1 mm. Such SHE using micro-tubes are highly effective for high flux heat transfer technologies. Nanofluids, are used to enhance the thermal conductivity of re-circulated coolant and thus enhances heat transfer rate further. Higher viscosity associated with nanofluid expands more pumping power. Thus, there is a trade-off between heat transfer rate and pressure drop with geometry of micro-tubes. Herein, a novel design of short counter flow heat exchanger (SCFHE) using non-circular micro-tubes flooded with CuO-water nanofluid is conceptualized by varying the ratio of surface area to cross-sectional area of micro-tubes. A framework for comparative analysis of SCFHE using micro-tubes non-circular shape flooded by CuO-water nanofluid is presented. In SCFHE concept, micro-tubes having various geometrical shapes (viz., triangular, rectangular and trapezoidal) has been arranged row-wise to facilitate two aspects: (1) allowing easy flow distribution for cold and hot stream, and (2) maximizing the thermal interactions with neighboring channels. Adequate distribution of rows for cold and hot flow streams enables above two aspects. For comparative analysis, a specific volume or cross-section area is assigned to each elemental cell (which includes flow area and area corresponds to half wall thickness). A specific volume or cross-section area is assumed to be constant for each elemental cell (which includes flow area and half wall thickness area) and variation in surface area is allowed by selecting different geometry of micro-tubes in SCFHE. Effective thermal conductivity model for CuO-water nanofluid has been adopted, while the viscosity values for water based nanofluids are obtained empirically. Correlations for Nusselt number (Nu) and Poiseuille number (Po) for micro-tubes have been derived or adopted. Entrance effect is accounted for. Thermal and hydrodynamic performances of SCFHE are defined in terms of effectiveness and pressure drop or pumping power, respectively. For defining the overall performance index of SCFHE, two links are employed. First one relates heat transfer between the fluid streams q and pumping power PP as (=qj/PPj); while another link relates effectiveness eff and pressure drop dP as (=effj/dPj). For analysis, the inlet temperatures of hot and cold streams are varied in usual range of 20dC-65dC. Fully turbulent regime is seldom encountered in micro-tubes and transition of flow regime occurs much early (i.e., ~Re=1000). Thus, Re is fixed at 900, however, the uncertainty in Re due to addition of nanoparticles in base fluid is quantified by averaging of Re. Moreover, for minimizing error, volumetric concentration is limited to range 0% to ≤4% only. Such framework may be helpful in utilizing maximum peripheral surface area of SCFHE without any serious severity on pumping power and towards developing advanced short heat exchangers.

Keywords: CuO-water nanofluid, non-circular micro-tubes, performance index, short counter flow heat exchanger

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Authors: Michal Kielbik, Izabela Szulc-Kielbik, Anna Brzostek, Jaroslaw Dziadek, Magdalena Klink

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The goal of many research groups in the world is to find new components that are important for survival of mycobacteria in the host cells. Mycobacterium tuberculosis (Mtb) possesses a number of enzymes degrading cholesterol that are considered to be an important factor for its survival and persistence in host macrophages. One of them - cholesterol oxidase (ChoD), although not being essential for cholesterol degradation, is discussed as a virulence compound, however its involvement in macrophages’ response to Mtb is still not sufficiently determined. The recognition of tubercle bacilli antigens by pathogen recognition receptors is crucial for the initiation of the host innate immune response. An important receptor that has been implicated in the recognition and/or uptake of Mtb is Toll-like receptor type 2 (TLR2). Engagement of TLR2 results in the activation and phosphorylation of intracellular signaling proteins including IRAK-1 and -4, TRAF-6, which in turn leads to the activation of target kinases and transcription factors responsible for bactericidal and pro-inflammatory response of macrophages. The aim of these studies was a detailed clarification of the role of Mtb cholesterol oxidase as a virulence factor affecting the TLR2 signaling pathway in human macrophages. As human macrophages the THP-1 differentiated cells were applied. The virulent wild-type Mtb strain (H37Rv), its mutant lacking a functional copy of gene encoding cholesterol oxidase (∆choD), as well as complimented strain (∆choD–choD) were used. We tested the impact of Mtb strains on the expression of TLR2-depended signaling proteins (mRNA level, cytosolic level and phosphorylation status). The cytokine and bactericidal response of THP-1 derived macrophages infected with Mtb strains in relation to TLR2 signaling pathway dependence was also determined. We found that during the 24-hours of infection process the wild-type and complemented Mtb significantly reduced the cytosolic level and phosphorylation status of IRAK-4 and TRAF-6 proteins in macrophages, that was not observed in the case of ΔchoD mutant. Decreasement of TLR2-dependent signaling proteins, induced by wild-type Mtb, was not dependent on the activity of proteasome. Blocking of TLR2 expression, before infection, effectively prevented the induced by wild-type strain reduction of cytosolic level and phosphorylation of IRAK-4. None of the strains affected the surface expression of TLR2. The mRNA level of IRAK-4 and TRAF-6 genes were significantly increased in macrophages 24 hours post-infection with either of tested strains. However, the impact of wild-type Mtb strain on both examined genes was significantly stronger than its ΔchoD mutant. We also found that wild-type strain stimulated macrophages to release high amount of immunosuppressive IL-10, accompanied by low amount of pro-inflammatory IL-8 and bactericidal nitric oxide in comparison to mutant lacking cholesterol oxidase. The influence of wild-type Mtb on this type of macrophages' response strongly dependent on fully active IRAK-1 and IRAK-4 signaling proteins. In conclusion, Mtb using cholesterol oxidase causes the over-activation of TLR2 signaling proteins leading to the reduction of their cytosolic level and activity resulting in the modulation of macrophages response to allow its intracellular survival. Supported by grant: 2014/15/B/NZ6/01565, National Science Center, Poland

Keywords: Mycobacterium tuberculosis, cholesterol oxidase, macrophages, TLR2-dependent signaling pathway

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Authors: Ankit Khurana

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The sufficient heat storage capacity or ability to dissipate heat is the most decisive parameter to have an effective and efficient functioning of Friction-based Brake Disc systems. The primary aim of the research was to analyse the effect of multiple coatings on lightweight disk rotors surface which not only alleviates the mass of vehicle & also, augments heat transfer. This research is projected to aid the automobile fraternity with an enunciated view over the thermal aspects in a braking system. The results of the project indicate that with the advent of modern coating technologies a brake system’s thermal curtailments can be removed and together with forced convection, heat transfer processes can see a drastic improvement leading to increased lifetime of the brake rotor. Other advantages of modifying the surface of a lightweight rotor substrate will be to reduce the overall weight of the vehicle, decrease the risk of thermal brake failure (brake fade and fluid vaporization), longer component life, as well as lower noise and vibration characteristics. A mathematical model was constructed in MATLAB which encompassing the various thermal characteristics of the proposed coatings and substrate materials required to approximate the heat flux values in a free and forced convection environment; resembling to a real-time braking phenomenon which could easily be modelled into a full cum scaled version of the alloy brake rotor part in ABAQUS. The finite element of a brake rotor was modelled in a constrained environment such that the nodal temperature between the contact surfaces of the coatings and substrate (Wrought Aluminum alloy) resemble an amalgamated solid brake rotor element. The initial results obtained were for a Plasma Electrolytic Oxidized (PEO) substrate wherein the Aluminum alloy gets a hard ceramic oxide layer grown on its transitional phase. The rotor was modelled and then evaluated in real-time for a constant ‘g’ braking event (based upon the mathematical heat flux input and convective surroundings), which reflected the necessity to deposit a conducting coat (sacrificial) above the PEO layer in order to inhibit thermal degradation of the barrier coating prematurely. Taguchi study was then used to bring out certain critical factors which may influence the maximum operating temperature of a multi-coated brake disc by simulating brake tests: a) an Alpine descent lasting 50 seconds; b) an Autobahn stop lasting 3.53 seconds; c) a Six–high speed repeated stop in accordance to FMVSS 135 lasting 46.25 seconds. Thermal Barrier coating thickness and Vane heat transfer coefficient were the two most influential factors and owing to their design and manufacturing constraints a final optimized model was obtained which survived the 6-high speed stop test as per the FMVSS -135 specifications. The simulation data highlighted the merits for preferring Wrought Aluminum alloy 7068 over Grey Cast Iron and Aluminum Metal Matrix Composite in coherence with the multiple coating depositions.

Keywords: lightweight brakes, surface modification, simulated braking, PEO, aluminum

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Authors: K. Ghosh, S. N. Tripathi, Manish Joshi, Y. S. Mayya, Arshad Khan, B. K. Sapra

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We have developed a CFD coupled aerosol microphysics model in the context of aerosol generation from a glowing wire. The governing equations can be solved implicitly for mass, momentum, energy transfer along with aerosol dynamics. The computationally efficient framework can simulate temporal behavior of total number concentration and number size distribution. This formulation uniquely couples standard K-Epsilon scheme with boundary layer model with detailed aerosol dynamics through residence time. This model uses measured temperatures (wire surface and axial/radial surroundings) and wire compositional data apart from other usual inputs for simulations. The model predictions show that bulk fluid motion and local heat distribution can significantly affect the aerosol behavior when the buoyancy effect in momentum transfer is considered. Buoyancy generated turbulence was found to be affecting parameters related to aerosol dynamics and transport as well. The model was validated by comparing simulated predictions with results obtained from six controlled experiments performed with a laboratory-made hot wire nanoparticle generator. Condensation particle counter (CPC) and scanning mobility particle sizer (SMPS) were used for measurement of total number concentration and number size distribution at the outlet of reactor cell during these experiments. Our model-predicted results were found to be in reasonable agreement with observed values. The developed model is fast (fully implicit) and numerically stable. It can be used specifically for applications in the context of the behavior of aerosol particles generated from glowing wire technique and in general for other similar large scale domains. Incorporation of CFD in aerosol microphysics framework provides a realistic platform to study natural convection driven systems/ applications. Aerosol dynamics sub-modules (nucleation, coagulation, wall deposition) have been coupled with Navier Stokes equations modified to include buoyancy coupled K-Epsilon turbulence model. Coupled flow-aerosol dynamics equation was solved numerically and in the implicit scheme. Wire composition and temperature (wire surface and cell domain) were obtained/measured, to be used as input for the model simulations. Model simulations showed a significant effect of fluid properties on the dynamics of aerosol particles. The role of buoyancy was highlighted by observation and interpretation of nucleation zones in the planes above the wire axis. The model was validated against measured temporal evolution, total number concentration and size distribution at the outlet of hot wire generator cell. Experimentally averaged and simulated total number concentrations were found to match closely, barring values at initial times. Steady-state number size distribution matched very well for sub 10 nm particle diameters while reasonable differences were noticed for higher size ranges. Although tuned specifically for the present context (i.e., aerosol generation from hotwire generator), the model can also be used for diverse applications, e.g., emission of particles from hot zones (chimneys, exhaust), fires and atmospheric cloud dynamics.

Keywords: nanoparticles, k-epsilon model, buoyancy, CFD, hot wire generator, aerosol dynamics

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Authors: Ekta Yadav, Sukanta Bhattacharya, Brijesh Yadav, Ariel Hus, Jagjit Yadav

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Background and Significance: Respiratory exposure to toxicants (chemicals or particulates) causes disruption of lung homeostasis leading to lung toxicity/injury manifested as pulmonary inflammation, edema, and/or other effects depending on the type and extent of exposure. This emphasizes the need for investigating toxicant type-specific mechanisms to understand therapeutic targets. Aquaporins, aka water channels, are known to play a role in lung homeostasis. Particularly, the two major lung aquaporins AQP5 and AQP1 expressed in alveolar epithelial and vasculature endothelia respectively allow for movement of the fluid between the alveolar air space and the associated vasculature. In view of this, the current study is focused on understanding the regulation of lung aquaporins and other targets during inhalation exposure to toxic chemicals (Cigarette smoke chemicals) versus toxic particles (Carbon nanoparticles) or co-exposures to understand their relevance as markers of injury and intervention. Methodologies: C57BL/6 mice (5-7 weeks old) were used in this study following an approved protocol by the University of Cincinnati Institutional Animal Care and Use Committee (IACUC). The mice were exposed via oropharyngeal aspiration to multiwall carbon nanotube (MWCNT) particles suspension once (33 ugs/mouse) followed by housing for four weeks or to Cigarette smoke Extract (CSE) using a daily dose of 30µl/mouse for four weeks, or to co-exposure using the combined regime. Control groups received vehicles following the same dosing schedule. Lung toxicity/injury was assessed in terms of homeostasis changes in the lung tissue and lumen. Exposed lungs were analyzed for transcriptional expression of specific targets (AQPs, surfactant protein A, Mucin 5b) in relation to tissue homeostasis. Total RNA from lungs extracted using TRIreagent kit was analyzed using qRT-PCR based on gene-specific primers. Total protein in bronchoalveolar lavage (BAL) fluid was determined by the DC protein estimation kit (BioRad). GraphPad Prism 5.0 (La Jolla, CA, USA) was used for all analyses. Major findings: CNT exposure alone or as co-exposure with CSE increased the total protein content in the BAL fluid (lung lumen rinse), implying compromised membrane integrity and cellular infiltration in the lung alveoli. In contrast, CSE showed no significant effect. AQP1, required for water transport across membranes of endothelial cells in lungs, was significantly upregulated in CNT exposure but downregulated in CSE exposure and showed an intermediate level of expression for the co-exposure group. Both CNT and CSE exposures had significant downregulating effects on Muc5b, and SP-A expression and the co-exposure showed either no significant effect (Muc5b) or significant downregulating effect (SP-A), suggesting an increased propensity for infection in the exposed lungs. Conclusions: The current study based on the lung toxicity mouse model showed that both toxicant types, particles (CNT) versus chemicals (CSE), cause similar downregulation of lung innate defense targets (SP-A, Muc5b) and mostly a summative effect when presented as co-exposure. However, the two toxicant types show differential induction of aquaporin-1 coinciding with the corresponding differential damage to alveolar integrity (vascular permeability). Interestingly, this implies the potential of AQP1 as a differential marker of toxicant type-specific lung injury.

Keywords: aquaporin, gene expression, lung injury, toxicant exposure

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Authors: Tom S. Owens, Tom A. Calverley, Benjamin S. Stacey, Christopher J. Marley, George Rose, Lewis Fall, Gareth L. Jones, Priscilla Williams, John P. R. Williams, Martin Steggall, Damian M. Bailey

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Introduction and aims: Sports-related concussion (SRC) represents a significant and growing public health concern in rugby union, yet remains one of the least understood injuries facing the health community today. Alongside increasing SRC incidence rates, there is concern that prior recurrent concussion may contribute to long-term neurologic sequelae in later-life. This may be due to an accelerated decline in cerebral perfusion, a major risk factor for neurocognitive decline and neurodegeneration, though the underlying mechanisms remain to be established. The present study hypothesised that recurrent concussion in current professional rugby union players would result in elevated systemic oxidative-nitrosative stress, reflected by a free radical-mediated reduction in nitric oxide (NO) bioavailability and impaired cerebrovascular and cognitive function. Methodology: A longitudinal study design was adopted across the 2017-2018 rugby union season. Ethical approval was obtained from the University of South Wales Ethics Committee. Data collection is ongoing, and therefore the current report documents result from the pre-season and first half of the in-season data collection. Participants were initially divided into two subgroups; 23 professional rugby union players (aged 26 ± 5 years) and 22 non-concussed controls (27 ± 8 years). Pre-season measurements were performed for cerebrovascular function (Doppler ultrasound of middle cerebral artery velocity (MCAv) in response to hypocapnia/normocapnia/hypercapnia), cephalic venous concentrations of the ascorbate radical (A•-, electron paramagnetic resonance spectroscopy), NO (ozone-based chemiluminescence) and cognition (neuropsychometric tests). Notational analysis was performed to assess contact in the rugby group throughout each competitive game. Results: 1001 tackles and 62 injuries, including three concussions were observed across the first half of the season. However, no associations were apparent between number of tackles and any injury type (P > 0.05). The rugby group expressed greater oxidative stress as indicated by increased A•- (P < 0.05 vs. control) and a subsequent decrease in NO bioavailability (P < 0.05 vs. control). The rugby group performed worse in the Ray Auditory Verbal Learning Test B (RAVLT-B, learning, and memory) and the Grooved Pegboard test using both the dominant and non-dominant hands (visuomotor coordination, P < 0.05 vs. control). There were no between-group differences in cerebral perfusion at baseline (MCAv: 54 ± 13 vs. 59 ± 12, P > 0.05). Likewise, no between-group differences in CVRCO2Hypo (2.58 ± 1.01 vs. 2.58 ± 0.75, P > 0.05) or CVRCO2Hyper (2.69 ± 1.07 vs. 3.35 ± 1.28, P > 0.05) were observed. Conclusion: The present study identified that the rugby union players are characterized by impaired cognitive function subsequent to elevated systemic-oxidative-nitrosative stress. However, this appears to be independent of any functional impairment in cerebrovascular function. Given the potential long-term trajectory towards accelerated cognitive decline in populations exposed to SRC, prophylaxis to increase NO bioavailability warrants consideration.

Keywords: cognition, concussion, mild traumatic brain injury, rugby

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Authors: Amandeep Thakur, Yi-Hsuan Chu, Chun-Hsu Pan, Kunal Nepali

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The transfer of ADP-ribose residues onto target substrates from nicotinamide adenine dinucleotide (NAD) (PARylation) is catalyzed by Poly (ADP-ribose) polymerases (PARPs). Amongst the PARP family members, the DNA damage response in cancer is majorly regulated by PARP1 and PARP2. The blockade of DNA repair by PARP inhibitors leads to the progression of DNA single-strand breaks (induced by some triggering factors) to double-strand breaks. Notably, PARP inhibitors are remarkably effective in cancers with defective homologous recombination repair (HRR). In particular, cancer cells with BRCA mutations are responsive to therapy with PARP inhibitors. The aforementioned requirement for PARP inhibitors to be effective confers a narrow activity spectrum to PARP inhibitors, which hinders their clinical applicability. Thus, the quest to expand the application horizons of PARP inhibitors beyond BRCA mutations is the need of the hour. Literature precedents reveal that HDAC inhibition induces BRCAness in cancer cells and can broaden the therapeutic scope of PARP inhibitors. Driven by such disclosures, dual inhibitors targeting both PARP and HDAC enzymes were designed by our research group to extend the efficacy of PARP inhibitors beyond BRCA-mutated cancers to cancers with induced BRCAness. The design strategy involved the installation of Veliparib, an investigational PARP inhibitor, as a surface recognition part in the HDAC inhibitor pharmacophore model. The chemical architecture of veliparib was deemed appropriate as a starting point for the generation of dual inhibitors by virtue of its size and structural flexibility. A validatory docking study was conducted at the outset to predict the binding mode of the designed dual modulatory chemical architectures. Subsequently, the designed chemical architectures were synthesized via a multistep synthetic route and evaluated for antitumor efficacy. Delightfully, one compound manifested impressive anti-leukemic effects (HL-60 cell lines) mediated via dual inhibition of PARP and class I HDACs. The outcome of the western blot analysis revealed that the compound could downregulate the expression levels of PARP1 and PARP2 and the HDAC isoforms (HDAC1, 2, and 3). Also, the dual PARP-HDAC inhibitor upregulated the protein expression of the acetyl histone H3, confirming its abrogation potential for class I HDACs. In addition, the dual modulator could arrest the cell cycle at the G0/G1 phase and induce autophagy. Further, polymer-based nanoformulation of the dual inhibitor was furnished to afford targeted delivery of the dual inhibitor at the cancer site. Transmission electron microscopy (TEM) results indicate that the nanoparticles were monodispersed and spherical. Moreover, the polymeric nanoformulation exhibited an appropriate particle size. Delightfully, pH-sensitive behavior was manifested by the polymeric nanoformulation that led to selective antitumor effects towards the HL-60 cell lines. In light of the magnificent anti-leukemic profile of the identified dual PARP-HDAC inhibitor, in-vivo studies (pharmacokinetics and pharmacodynamics) are currently being conducted. Notably, the optimistic findings of the aforementioned study have spurred our research group to initiate several medicinal chemistry campaigns to create bifunctional small molecule inhibitors addressing PARP as the primary target.

Keywords: PARP inhibitors, HDAC inhibitors, BRCA mutations, leukemia

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Authors: Kuladip Jana

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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased ROS, altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38MAPK, cytosolic translocation of cytochrome-c, up-regulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of PARP and down-regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like StAR, cytochrome P450 IIA1 (CYPIIA1), 3β HSD, 17β HSD showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis.The possible protective role of naturally occurring phytochemicals against B(a)P induced testicular toxicity needs immediate consideration. Curcumin and resveratrol separately were found to protect against B(a)P induced germ cell apoptosis, and their combinatorial effect was more significant. Our present study in isolated testicular germ cell population from adult male Wistar rats, highlighted their synergistic protective effect against B(a)P induced germ cell apoptosis. Curcumin-resveratrol co-treatment decreased the expression of pro-apoptotic proteins like cleaved caspase 3,8,9, cleaved PARP, Apaf1, FasL, tBid. Curcumin-resveratrol co-treatment decreased Bax/Bcl2 ratio, mitochondria to cytosolic translocation of cytochrome c and activated the survival protein Akt. Curcumin-resveratrol decreased the expression of p53 dependent apoptotic genes like Fas, FasL, Bax, Bcl2, Apaf1.Curcumin-resveratrol co-treatment thus prevented B(a)P induced germ cell apoptosis. B(a)P induced testicular ROS generation and oxidative stress were significantly ameliorated with curcumin and resveratrol. Curcumin-resveratrol co-treatment prevented B(a)P induced nuclear translocation of AhR and CYP1A1 production. The combinatorial treatment significantly inhibited B(a)P induced ERK 1/2, p38 MAPK and JNK 1/2 activation. B(a)P treatment increased the expression of p53 and its phosphorylation (p53 ser 15). Curcumin-resveratrol co-treatment significantly decreased p53 level and its phosphorylation (p53 ser 15). The study concludes that curcumin-resveratrol synergistically modulated MAPKs and p53, prevented oxidative stress, regulated the expression of pro and anti-apoptotic proteins as well as the proteins involved in B(a)P metabolism thus protected germ cells from B(a)P induced apoptosis.

Keywords: benzo(a)pyrene, germ cell, apoptosis, oxidative stress, resveratrol, curcumin

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