Search results for: free surface sloshing

Authors: Aiman Mazhar Qureshi, Ahmed Rachid

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Extreme heat events are emerging human environmental health concerns in dense urban areas due to anthropogenic activities. High spatial and temporal resolution heat maps are important for urban heat adaptation and mitigation, helping to indicate hotspots that are required for the attention of city planners. The Heat Vulnerability Index (HVI) is the important approach used by decision-makers and urban planners to identify heat-vulnerable communities and areas that require heat stress mitigation strategies. Amiens is a medium-sized French city, where the average temperature has been increasing since the year 2000 by +1°C. Extreme heat events are recorded in the month of July for the last three consecutive years, 2018, 2019 and 2020. Poor air quality, especially ground-level ozone, has been observed mainly during the same hot period. In this study, we evaluated the HVI in Amiens during extreme heat days recorded last three years (2018,2019,2020). The Principal Component Analysis (PCA) technique is used for fine-scale vulnerability mapping. The main data we considered for this study to develop the HVI model are (a) socio-economic and demographic data; (b) Air pollution; (c) Land use and cover; (d) Elderly heat-illness; (e) socially vulnerable; (f) Remote sensing data (Land surface temperature (LST), mean elevation, NDVI and NDWI). The output maps identified the hot zones through comprehensive GIS analysis. The resultant map shows that high HVI exists in three typical areas: (1) where the population density is quite high and the vegetation cover is small (2) the artificial surfaces (built-in areas) (3) industrial zones that release thermal energy and ground-level ozone while those with low HVI are located in natural landscapes such as rivers and grasslands. The study also illustrates the system theory with a causal diagram after data analysis where anthropogenic activities and air pollution appear in correspondence with extreme heat events in the city. Our suggested index can be a useful tool to guide urban planners and municipalities, decision-makers and public health professionals in targeting areas at high risk of extreme heat and air pollution for future interventions adaptation and mitigation measures.

Keywords: heat vulnerability index, heat mapping, heat health-illness, remote sensing, urban heat mitigation

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Authors: Johannes Günther

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Time Sensitive Networking (TSN), standardized in the IEEE 802.1 standard, has been lent increasing attention in the context of mission critical systems. Such mission critical systems, e.g., in the automotive domain, aviation, industrial, and smart factory domain, are responsible for coordinating complex functionalities in real time. In many of these contexts, a reliable data exchange fulfilling hard time constraints and quality of service (QoS) conditions is of critical importance. TSN standards are able to provide guarantees for deterministic communication behaviour, which is in contrast to common best-effort approaches. Therefore, the superior QoS guarantees of TSN may aid in the development of new technologies, which rely on low latencies and specific bandwidth demands being fulfilled. TSN extends existing Ethernet protocols with numerous standards, providing means for synchronization, management, and overall real-time focussed capabilities. These additional QoS guarantees, as well as management mechanisms, lead to an increased attack surface for potential malicious attackers. As TSN guarantees certain deadlines for priority traffic, an attacker may degrade the QoS by delaying a packet beyond its deadline or even execute a denial of service (DoS) attack if the delays lead to packets being dropped. However, thus far, security concerns have not played a major role in the design of such standards. Thus, while TSN does provide valuable additional characteristics to existing common Ethernet protocols, it leads to new attack vectors on networks and allows for a range of potential attacks. One answer to these security risks is to deploy defense mechanisms according to a moving target defense (MTD) strategy. The core idea relies on the reduction of the attackers' knowledge about the network. Typically, mission-critical systems suffer from an asymmetric disadvantage. DoS or QoS-degradation attacks may be preceded by long periods of reconnaissance, during which the attacker may learn about the network topology, its characteristics, traffic patterns, priorities, bandwidth demands, periodic characteristics on links and switches, and so on. Here, we implemented and tested several MTD-like defense strategies against different attacker models of varying capabilities and budgets, as well as collaborative attacks of multiple attackers within a network, all within the context of TSN networks. We modelled the networks and tested our defense strategies on an OMNET++ testbench, with networks of different sizes and topologies, ranging from a couple dozen hosts and switches to significantly larger set-ups.

Keywords: network security, time sensitive networking, moving target defense, cyber security

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Authors: Katerina Zaharieva, Vicente Rives, Martin Tsvetkov, Raquel Trujillano, Boris Kunev, Ivan Mitov, Maria Milanova, Zara Cherkezova-Zheleva

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The nanostructured cobalt ferrite-type materials Sample A - Co0.25Fe2.75O4, Sample B - Co0.5Fe2.5O4, and Sample C - CoFe2O4 were prepared by co-precipitation in our previous investigations. The co-precipitated Sample B and Sample C were mechanochemically activated in order to produce Sample D - Co0.5Fe2.5O4 and Sample E- CoFe2O4. The PXRD, Moessbauer and FTIR spectroscopies, specific surface area determination by the BET method, thermal analysis, element chemical analysis and temperature-programmed reduction were used to investigate the prepared nano-sized samples. The changes of the Malachite green dye concentration during reaction of the photocatalytic decolorization using nanostructured cobalt ferrite-type catalysts with different chemical composition are included. The photocatalytic results show that the increase in the degree of incorporation of cobalt ions in the magnetite host structure for co-precipitated cobalt ferrite-type samples results in an increase of the photocatalytic activity: Sample A (4 х10-3 min-1) < Sample B (5 х10-3 min-1) < Sample C (7 х10-3 min-1). Mechanochemically activated photocatalysts showed a higher activity than the co-precipitated ferrite materials: Sample D (16 х10-3 min-1) > Sample E (14 х10-3 min-1) > Sample C (7 х10-3 min-1) > Sample B (5 х10-3 min-1) > Sample A (4 х10-3 min-1). On decreasing the degree of substitution of iron ions by cobalt ones a higher sorption ability of the dye after the dark period for the co-precipitated cobalt ferrite materials was observed: Sample C (72 %) < Sample B (78 %) < Sample A (80 %). Mechanochemically treated ferrite catalysts and co-precipitated Sample B possess similar sorption capacities, Sample D (78 %) ~ Sample E (78 %) ~ Sample B (78 %). The prepared nano-sized cobalt ferrite-type materials demonstrate good photocatalytic and sorption properties. Mechanochemically activated Sample D - Co0.5Fe2.5O4 (16х10-3 min-1) and Sample E-CoFe2O4 (14х10-3 min-1) possess higher photocatalytic activity than that of the most common used UV-light catalyst Degussa P25 (12х10-3 min-1). The dependence of the photo-catalytic activity and sorption properties on the preparation method and different degree of substitution of iron ions by cobalt ions in synthesized cobalt ferrite samples is established. The mechanochemical activation leads to formation of nano-structured cobalt ferrite-type catalysts (Sample D and Sample E) with higher rate constants than those of the ferrite materials (Sample A, Sample B, and Sample C) prepared by the co-precipitation procedure. The increase in the degree of substitution of iron ions by cobalt ones leads to improved photocatalytic properties and lower sorption capacities of the co-precipitated ferrite samples. The good sorption properties between 72 and 80% of the prepared ferrite-type materials show that they could be used as potential cheap absorbents for purification of polluted waters.

Keywords: nanodimensional cobalt ferrites, photocatalyst, synthesis, mechanochemical activation

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Authors: Rachid Essamoud, Abdelkrim Afenzar, Ahmed Belqadi

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During the Early Mesozoic, the northwestern part of the African continent was affected by initial fracturing associated with the early stages of the opening of the Central Atlantic (Atlantic Rift). During this rifting phase, the Moroccan Meseta experienced an extensive tectonic regime. This extension favored the formation of a set of rift-type basins, including the Mohammedia-Benslimane-ElGara-Berrechid basin. Thus, it is essential to know the nature of the deposits in this basin and their evolution over time as well as their relationship with the basaltic effusion of the Central Atlantic Magmatic Province (CAMP). These deposits are subdivided into two large series: The Lower clay-salt series attributed to the Triassic and the Upper clay-salt series attributed to the Liassic. The two series are separated by the Upper Triassic-Lower Liassic basaltic complex. The detailed sedimentological analysis made it possible to characterize four mega-sequences, fifteen types of facies and eight architectural elements and facies associations in the Triassic series. A progressive decrease observed in paleo-slope over time led to the evolution of the paleoenvironment from a proximal system of alluvial fans to a braided fluvial style, then to an anastomosed system. These environments eventually evolved into an alluvial plain associated with a coastal plain where playa lakes, mudflats and lagoons had developed. The pure and massive halitic facies at the top of the series probably indicate an evolution of the depositional environment towards a shallow subtidal environment. The presence of these evaporites indicates a climate that favored their precipitation, in this case, a fairly hot and humid climate. The sedimentological analysis of the supra-basaltic part shows that during the Lower Liassic, the paleopente after basaltic effusion remained weak with distal environments. The faciological analysis revealed the presence of four major sandstone, silty, clayey and evaporitic lithofacies organized in two mega-sequences: the sedimentation of the first rock-salt mega-sequence took place in a brine depression system free, followed by saline mudflats under continental influences. The upper clay mega-sequence displays facies documenting sea level fluctuations from the final transgression of the Tethys or the opening Atlantic. Saliferous sedimentation is therefore favored from the Upper Triassic, but experienced a sudden rupture by the emission of basaltic flows which are interstratified in the azoic salt clays of very shallow seas. This basaltic emission which belongs to the CAMP would come from a fissural volcanism probably carried out through transfer faults located in the NW and SE of the basin. Their emplacement is probably subaquatic to subaerial. From a chronological and paleogeographic point of view, this main volcanism, dated between the Upper Triassic and the Lower Liassic (180-200 MA), is linked to the fragmentation of Pangea and managed by a progressive expansion triggered in the West in close relation with the initial phases of Central Atlantic rifting and seems to coincide with the major mass extinction at the Triassic-Jurassic boundary.

Keywords: Basalt, CAMP, Liassic, sedimentology, Triassic, Morocco

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Authors: Fatemeh Abbasi, Arne Hofemeier, Timo Betz

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Muscle growth and regeneration critically depend on satellite cells (SCs) which are muscle stem cells located between the basal lamina and myofibres. Upon damage, SCs become activated, enter the cell cycle, and give rise to myoblasts that form new myofibres, while a sub-population self-renew and re-populate the muscle stem cell niche. In aged muscle as well as in certain muscle diseases such as muscular dystrophy, some of the SCs lose their regenerative ability. Although it is demonstrated that the chemical composition of SCs quiescent niche is different from the activated niche, the mechanism initially activated in the SCs remains unknown. While extensive research efforts focused on potential chemical activation, no such factor has been identified to the author’s best knowledge. However, it is substantiated that niche mechanics affects SCs behaviors, such as stemness and engraftment. We hypothesize that mechanical stress in the healthy niche (homeostasis) is different from the regenerative niche and that this difference could serve as an early signal activating SCs upon fiber damage. To investigate this hypothesis, we develop a biomimetic system to reconstitute both, the mechanical and the chemical environment of the SC niche. Cells will be confined between two elastic polyacrylamide (PAA) hydrogels with controlled elastic moduli and functionalized surface chemistry. By controlling the distance between the PAA hydrogel surfaces, we vary the compression forces exerted by the substrates on the cells, while the lateral displacement of the upper hydrogel will create controlled shear forces. To establish such a system, a simplified system is presented. We engineered a sandwich-like configuration of two elastic PAA layer with stiffnesses between 1 and 10 kPa and confined a precursor myoblast cell line (C2C12) in between these layers. Our initial observations in this sandwich model indicate that C2C12 cells show different behaviors under mechanical compression if compared to a control one-layer gel without compression. Interestingly, this behavior is stiffness-dependent. While the shape of C2C12 cells in the sandwich consisting of two stiff (10 kPa) layers was much more elongated, showing almost a neuronal phenotype, the cell shape in a sandwich situation consisting of one stiff and one soft (1 kPa) layer was more spherical. Surprisingly, even in proliferation medium and at very low cell density, the sandwich situation stimulated cell differentiation with increased striation and myofibre formation. Such behavior is commonly found for confluent cells in differentiation medium. These results suggest that mechanical changes in stiffness and applied pressure might be a relevant stimulation for changes in muscle cell behavior.

Keywords: C2C12 cells, compression, force, satellite cells, skeletal muscle

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Authors: Anna Wolowicz, Katarzyna Staszak, Zbigniew Hubicki

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Nowadays heavy metal ions as well as surfactants are widely used throughout the world due to their useful properties. The consequence of such widespread use is their significant production. On the other hand, the increasing demand for surfactants and heavy metal ions results in production of large amounts of wastewaters which are discharged to the environment from mining, metal plating, pharmaceutical, cosmetic, fertilizer, paper, pesticide and electronic industries, pigments producing, petroleum refining and from autocatalyst, fibers, food, polymer industries etc. Heavy metal ions are non-biodegradable in the environment, cable of accumulation in living organisms and organs, toxic and carcinogenic. On the other hand, not only heavy metal ions but also surfactants affect the purity of water and soils. Some of surfactants are also toxic, harmful and dangerous because they are able to penetrate into surface waters causing foaming, blocked diffusion of oxygen from the atmosphere and act as emulsifiers of hydrophobic substances and increase solubility of many the dangerous pollutants. Among surfactants the anionic ones dominate and their share in the global production of surfactants is around 50 ÷ 60%. Due to the negative impact of heavy metals and surfactants on aquatic ecosystems and living organisms, removal and monitoring of their concentration in the environment is extremely important. Surfactants and heavy metal ions removal can be achieved by different biological and physicochemical methods. The adsorption as well as the ion-exchange methods play here a significant role. The aim of this study was heavy metal ions removal from aqueous solutions using different types of ion exchangers in the presence of anionic surfactants. Preliminary studies of copper(II), nickel(II), zinc(II) and cobalt(II) removal from acidic solutions using ion exchangers (Lewatit MonoPlus TP 220, Lewatit MonoPlus SR 7, Purolite A 400 TL, Purolite A 830, Purolite S 984, Dowex PSR 2, Dowex PSR3, Lewatit AF-5) allowed to select the most effective ones for the above mentioned sorbates and then to checking their removal efficiency in the presence of anionic surfactants. As it was found out Lewatit MonoPlus TP 220 of the chelating type, show the highest sorption capacities for copper(II) ions in comparison with the other ion exchangers under discussion, e.g. 9.98 mg/g (0.1 M HCl); 9.12 mg/g (6 M HCl). Moreover, cobalt(II) removal efficiency was the highest in 0.1 M HCl using also Lewatit MonoPlus TP 220 (6.9 mg/g) similar to zinc(II) (9.1 mg/g) and nickiel(II) (6.2 mg/g). As the anionic surfactant sodium dodecyl sulphate (SDS) was used and surfactant parameters such as viscosity (η), density (ρ) and critical micelle concentration (CMC) were obtained: η = 1.13 ± 0,01 mPa·s; ρ = 999.76 mg/cm3; CMC = 2.26 g/cm3. The studies of copper(II) removal from acidic solutions in the presence of SDS of different concentration show negligible effects on copper(II) removal efficiency. The sorption capacity of Cu(II) from 0.1 M acidic solution of 500 mg/L initial concentration was equal to 46.8 mg/g whereas in the presence of SDS 45.3 mg/g (0.1 mg SDS/L), 47.1 mg/g (0.5 mg SDS/L), 46.6 mg/g (1 mg SDS/L).

Keywords: anionic surfactant, heavy metal ions, ion exchanger, removal

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Authors: I. Nitoi, P. Oancea, M. Raileanu, M. Crisan, L. Constantin, I. Cristea

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Hazardous organic compounds like nitroaromatics are frequently found in chemical and petroleum industries discharged effluents. Due to their bio-refractory character and high chemical stability cannot be efficiently removed by classical biological or physical-chemical treatment processes. In the past decades, semiconductor photocatalysis has been frequently applied for the advanced degradation of toxic pollutants. Among various semiconductors titania was a widely studied photocatalyst, due to its chemical inertness, low cost, photostability and nontoxicity. In order to improve optical absorption and photocatalytic activity of TiO2 many attempts have been made, one feasible approach consists of doping oxide semiconductor with metal. The degradation of dinitrobenzene (DNB) and dinitrotoluene (DNT) from aqueous solution under UVA-VIS irradiation using heavy metal (0.5% Fe, 1%Co, 1%Ni ) doped titania was investigated. The photodegradation experiments were carried out using a Heraeus laboratory scale UV-VIS reactor equipped with a medium-pressure mercury lamp which emits in the range: 320-500 nm. Solutions with (0.34-3.14) x 10-4 M pollutant content were photo-oxidized in the following working conditions: pH = 5-9; photocatalyst dose = 200 mg/L; irradiation time = 30 – 240 minutes. Prior to irradiation, the photocatalyst powder was added to the samples, and solutions were bubbled with air (50 L/hour), in the dark, for 30 min. Dopant type, pH, structure and initial pollutant concentration influence on the degradation efficiency were evaluated in order to set up the optimal working conditions which assure substrate advanced degradation. The kinetics of nitroaromatics degradation and organic nitrogen mineralization was assessed and pseudo-first order rate constants were calculated. Fe doped photocatalyst with lowest metal content (0.5 wt.%) showed a considerable better behaviour in respect to pollutant degradation than Co and Ni (1wt.%) doped titania catalysts. For the same working conditions, degradation efficiency was higher for DNT than DNB in accordance with their calculated adsobance constants (Kad), taking into account that degradation process occurs on catalyst surface following a Langmuir-Hinshalwood model. The presence of methyl group in the structure of DNT allows its degradation by oxidative and reductive pathways, while DNB is converted only by reductive route, which also explain the highest DNT degradation efficiency. For highest pollutant concentration tested (3 x 10-4 M), optimum working conditions (0.5 wt.% Fe doped –TiO2 loading of 200 mg/L, pH=7 and 240 min. irradiation time) assures advanced nitroaromatics degradation (ηDNB=89%, ηDNT=94%) and organic nitrogen mineralization (ηDNB=44%, ηDNT=47%).

Keywords: hazardous organic compounds, irradiation, nitroaromatics, photocatalysis

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Authors: Olga V. Chervyakova, Elmira T. Tailakova, Vitaliy M. Strochkov, Kulyaisan T. Sultankulova, Nurlan T. Sandybayev, Lev G. Nemchinov, Rosemarie W. Hammond

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Sheep pox is a highly contagious infection that OIE regards to be one of the most dangerous animal diseases. It causes enormous economic losses because of death and slaughter of infected animals, lower productivity, cost of veterinary and sanitary as well as quarantine measures. To control spread of sheep pox infection the attenuated vaccines are widely used in the Republic of Kazakhstan and other Former Soviet Union countries. In spite of high efficiency of live vaccines, the possible presence of the residual virulence, potential genetic instability restricts their use in disease-free areas that leads to necessity to exploit new approaches in vaccine development involving recombinant DNA technology. Vaccines on the basis of recombinant proteins are the newest generation of prophylactic preparations. The main advantage of these vaccines is their low reactogenicity and this fact makes them widely used in medical and veterinary practice for vaccination of humans and farm animals. The objective of the study is to produce recombinant immunogenic proteins for development of the high-performance means for sheep pox prophylaxis. The SPV proteins were chosen for their homology with the known immunogenic vaccinia virus proteins. Assay of nucleotide and amino acid sequences of the target SPV protein genes. It has been shown that four proteins SPPV060 (ortholog L1), SPPV074 (ortholog H3), SPPV122 (ortholog A33) and SPPV141 (ortholog B5) possess transmembrane domains at N- or C-terminus while in amino acid sequences of SPPV095 (ortholog А 4) and SPPV117 (ortholog А 27) proteins these domains were absent. On the basis of these findings the primers were constructed. Target genes were amplified and subsequently cloned into the expression vector рЕТ26b(+) or рЕТ28b(+). Six constructions (pSPPV060ΔТМ, pSPPV074ΔТМ, pSPPV095, pSPPV117, pSPPV122ΔТМ and pSPPV141ΔТМ) were obtained for expression of the SPV genes under control of T7 promoter in Escherichia coli. To purify and detect recombinant proteins the amino acid sequences were modified by adding six histidine molecules at C-terminus. Induction of gene expression by IPTG was resulted in production of the proteins with molecular weights corresponding to the estimated values for SPPV060, SPPV074, SPPV095, SPPV117, SPPV122 and SPPV141, i.e. 22, 30, 20, 19, 17 and 22 kDa respectively. Optimal protocol of expression for each gene that ensures high yield of the recombinant protein was identified. Assay of cellular lysates by western blotting confirmed expression of the target proteins. Recombinant proteins bind specifically with antibodies to polyhistidine. Moreover all produced proteins are specifically recognized by the serum from experimentally SPV-infected sheep. The recombinant proteins SPPV060, SPPV074, SPPV117, SPPV122 and SPPV141 were also shown to induce formation of antibodies with virus-neutralizing activity. The results of the research will help to develop a new-generation high-performance means for specific sheep pox prophylaxis that is one of key moments in animal health protection. The research was conducted under the International project ISTC # K-1704 “Development of methods to construct recombinant prophylactic means for sheep pox with use of transgenic plants” and under the Grant Project RK MES G.2015/0115RK01983 "Recombinant vaccine for sheep pox prophylaxis".

Keywords: prophylactic preparation, recombinant protein, sheep pox virus, subunit vaccine

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Authors: Yudo Prasetyo, Hana Sugiastu Firdaus, Diyanah Diyanah

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The phenomenon of the lack of clean water supply in several big cities in Indonesia is a major problem in the development of urban areas. Moreover, in the city of Semarang, the population density and growth of physical development is very high. Continuous and large amounts of underground water (aquifer) exposure can result in a drastically aquifer supply declining in year by year. Especially, the intensity of aquifer use in the fulfilment of household needs and industrial activities. This is worsening by the land subsidence phenomenon in some areas in the Semarang city. Therefore, special research is needed to know the spatial correlation of the impact of decreasing aquifer capacity on the land subsidence phenomenon. This is necessary to give approve that the occurrence of land subsidence can be caused by loss of balance of pressure on below the land surface. One method to observe the correlation pattern between the two phenomena is the application of remote sensing technology based on radar and optical satellites. Implementation of Differential Interferometric Synthetic Aperture Radar (DINSAR) or Small Baseline Area Subset (SBAS) method in SENTINEL-1A satellite image acquisition in 2014-2017 period will give a proper pattern of land subsidence. These results will be spatially correlated with the aquifer-declining pattern in the same time period. Utilization of survey results to 8 monitoring wells with depth in above 100 m to observe the multi-temporal pattern of aquifer change capacity. In addition, the pattern of aquifer capacity will be validated with 2 underground water cavity maps from observation of ministries of energy and natural resources (ESDM) in Semarang city. Spatial correlation studies will be conducted on the pattern of land subsidence and aquifer capacity using overlapping and statistical methods. The results of this correlation will show how big the correlation of decrease in underground water capacity in influencing the distribution and intensity of land subsidence in Semarang city. In addition, the results of this study will also be analyzed based on geological aspects related to hydrogeological parameters, soil types, aquifer species and geological structures. The results of this study will be a correlation map of the aquifer capacity on the decrease in the face of the land in the city of Semarang within the period 2014-2017. So hopefully the results can help the authorities in spatial planning and the city of Semarang in the future.

Keywords: aquifer, differential interferometric synthetic aperture radar (DINSAR), land subsidence, small baseline area subset (SBAS)

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Authors: Sara R. Knigge, Sugat R. Tuladhar, Hans-Klaus HöFfler, Tobias Schilling, Tim Kaufeld, Axel Haverich

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Tissue engineered (TE) heart valves based on degradable electrospun fiber scaffold represent a promising approach to overcome the known limitations of mechanical or biological prostheses. But the mechanical stress in the high-pressure system of the human circulation is a severe challenge for the delicate materials. Hence, the prediction of the scaffolds` in vivo degradation kinetics must be as accurate as possible to prevent fatal events in future animal or even clinical trials. Therefore, this study investigates whether long-term testing in full blood provides more meaningful results regarding the degradation behavior than conventional tests in simulated body fluids (SBF) or Phosphate Buffered Saline (PBS). Fiber mats were produced from a polycaprolactone (PCL)/tetrafluoroethylene solution by electrospinning. The morphology of the fiber mats was characterized via scanning electron microscopy (SEM). A maximum physiological degradation environment utilizing a test set-up with porcine full blood was established. The set-up consists of a reaction vessel, an oxygenator unit, and a roller pump. The blood parameters (pO2, pCO2, temperature, and pH) were monitored with an online test system. All tests were also carried out in the test circuit with SBF and PBS to compare conventional degradation media with the novel full blood setting. The polymer's degradation is quantified by SEM picture analysis, differential scanning calorimetry (DSC), and Raman spectroscopy. Tensile and cyclic loading tests were performed to evaluate the mechanical integrity of the scaffold. Preliminary results indicate that PCL degraded slower in full blood than in SBF and PBS. The uptake of water is more pronounced in the full blood group. Also, PCL preserved its mechanical integrity longer when degraded in full blood. Protein absorption increased during the degradation process. Red blood cells, platelets, and their aggregates adhered on the PCL. Presumably, the degradation led to a more hydrophilic polymeric surface which promoted the protein adsorption and the blood cell adhesion. Testing degradable implants in full blood allows for developing more reliable scaffold materials in the future. Material tests in small and large animal trials thereby can be focused on testing candidates that have proven to function well in an in-vivo-like setting.

Keywords: Electrospun scaffold, full blood degradation test, long-term polymer degradation, tissue engineered aortic heart valve

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Authors: Sulalit Bandyopadhyay, Muhammad Awais Ashfaq Alvi, Anuvansh Sharma, Wilhelm R. Glomm

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Release of drugs from nanogels and nanogel-based systems can occur under the influence of external stimuli like temperature, pH, magnetic fields and so on. pNIPAm-AAc nanogels respond to the combined action of both temperature and pH, the former being mostly determined by hydrophilic-to-hydrophobic transitions above the volume phase transition temperature (VPTT), while the latter is controlled by the degree of protonation of the carboxylic acid groups. These nanogels based systems are promising candidates in the field of drug delivery. Combining nanogels with magneto-plasmonic nanoparticles (NPs) introduce imaging and targeting modalities along with stimuli-response in one hybrid system, thereby incorporating multifunctionality. Fe@Au core-shell NPs possess optical signature in the visible spectrum owing to localized surface plasmon resonance (LSPR) of the Au shell, and superparamagnetic properties stemming from the Fe core. Although there exist several synthesis methods to control the size and physico-chemical properties of pNIPAm-AAc nanogels, yet, there is no comprehensive study that highlights the dependence of incorporation of one or more layers of NPs to these nanogels. In addition, effective determination of volume phase transition temperature (VPTT) of the nanogels is a challenge which complicates their uses in biological applications. Here, we have modified the swelling-collapse properties of pNIPAm-AAc nanogels, by combining with Fe@Au NPs using different solution based methods. The hydrophilic-hydrophobic transition of the nanogels above the VPTT has been confirmed to be reversible. Further, an analytical method has been developed to deduce the average VPTT which is found to be 37.3°C for the nanogels and 39.3°C for nanogel coated Fe@Au NPs. An opposite swelling –collapse behaviour is observed for the latter where the Fe@Au NPs act as bridge molecules pulling together the gelling units. Thereafter, Cyt C, a model protein drug and L-Dopa, a drug used in the clinical treatment of Parkinson’s disease were loaded separately into the nanogels and nanogel coated Fe@Au NPs, using a modified breathing-in mechanism. This gave high loading and encapsulation efficiencies (L Dopa: ~9% and 70µg/mg of nanogels, Cyt C: ~30% and 10µg/mg of nanogels respectively for both the drugs. The release kinetics of L-Dopa, monitored using UV-vis spectrophotometry was observed to be rather slow (over several hours) with highest release happening under a combination of high temperature (above VPTT) and acidic conditions. However, the release of L-Dopa from nanogel coated Fe@Au NPs was the fastest, accounting for release of almost 87% of the initially loaded drug in ~30 hours. The chemical structure of the drug, drug incorporation method, location of the drug and presence of Fe@Au NPs largely alter the drug release mechanism and the kinetics of these nanogels and Fe@Au NPs coated with nanogels.

Keywords: controlled release, nanogels, volume phase transition temperature, l-dopa

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Authors: Evanka Madan, Madhu Puri, Dan Zilberstein, Rohini Muthuswami, Rentala Madhubala

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The extensive interaction between the host and pathogen metabolic networks decidedly shapes the outcome of infection. Utilization of arginine by the host and pathogen is critical for determining the outcome of pathogenic infection. Infections with L. donovani, an intracellular parasite, will lead to an extensive competition of arginine between the host and the parasite donovani infection. One of the major amino acid (AA) sensing signaling pathways in mammalian cells are the mammalian target of rapamycin complex I (mTORC1) pathway. mTORC1, as a sensor of nutrient, controls numerous metabolic pathways. Arginine is critical for mTORC1 activation. SLC38A9 is the arginine sensor for the mTORC1, being activated during arginine sufficiency. L. donovani transport arginine via a high-affinity transporter (LdAAP3) that is rapidly up-regulated by arginine deficiency response (ADR) in intracellular amastigotes. This study, to author’s best knowledge, investigates the interaction between two arginine sensing systems that act in the same compartment, the lysosome. One is important for macrophage defense, and the other is essential for pathogen virulence. We hypothesize that the latter modulates lysosome arginine to prevent host defense response. The work presented here identifies an upstream regulatory role of LdAAP3 in regulating the expression of SLC38A9-mTORC1 pathway, and consequently, their function in L. donovani infected THP-1 cells cultured in 0.1 mM and 1.5 mM arginine. It was found that in physiological levels of arginine (0.1 mM), infecting THP-1 with Leishmania leads to increased levels of SLC38A9 and mTORC1 via an increase in the expression of RagA. However, the reversal was observed with LdAAP3 mutants, reflecting the positive regulatory role of LdAAP3 on the host SLC38A9. At the molecular level, upon infection, mTORC1 and RagA were found to be activated at the surface of phagolysosomes which was found to form a complex with phagolysosomal localized SLC38A9. To reveal the relevance of SLC38A9 under physiological levels of arginine, endogenous SLC38A9 was depleted and a substantial reduction in the expression of host mTORC1, its downstream active substrate, p-P70S6K1 and parasite LdAAP3, was observed, thereby showing that silencing SLC38A9 suppresses ADR. In brief, to author’s best knowledge, these results reveal an upstream regulatory role of LdAAP3 in manipulating SLC38A9 arginine sensing in host macrophages. Our study indicates that intra-macrophage survival of L. donovani depends on the availability and transport of extracellular arginine. An understanding of the sensing pathway of both parasite and host will open a new perspective on the molecular mechanism of host-parasite interaction and consequently, as a treatment for Leishmaniasis.

Keywords: arginine sensing, LdAAP3, L. donovani, mTORC1, SLC38A9, THP-1

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Authors: Clementine Colpaert, Boris L. Nikitenko

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The Upper Jurassic foraminiferal assemblages of the East European Platform have been strongly investigated through the 20th century with biostratigraphical and in smaller degree palaeoecological and palaeobiogeographical purposes. Over the Late Jurassic, the platform was a shallow epicontinental sea that extended from Tethys to the Artic through the Pechora Sea and further toward the northeast in the West Siberian Sea. Foraminiferal assemblages of the Russian Sea were strongly affected by sea-level changes and were controlled by alternated Boreal to Peritethyan influences. The central part of the East European Platform displays very rich and diverse foraminiferal assemblages. Two sections have been analyzed; the Makar'yev Section in the Moscow Depression and the Gorodishi Section in the Yl'yanovsk Depression. Based on the evolution of foraminiferal assemblages, palaeoenvironment has been reconstructed, and sea-level changes have been refined. The aim of this study is to understand palaeoceanographical changes throughout the Oxfordian – Kimmeridgian of the central part of the Russian Sea. The Oxfordian was characterized by a general transgressive event with intermittency of small regressive phases. The platform was connected toward the south with Tethys and Peritethys. During the Middle Oxfordian, opening of a pathway of warmer water from the North-Tethys region to the Boreal Realm favoured the migration of planktonic foraminifera and the appearance of new benthic taxa. It is associated with increased temperature and primary production. During the Late Oxfordian, colder water inputs associated with the microbenthic community crisis may be a response to the closure of this warm-water corridor and the disappearance of planktonic foraminifera. The microbenthic community crisis is probably due to the increased sedimentation rate in the transition from the maximum flooding surface to a second-order regressive event, increasing productivity and inputs of organic matter along with sharp decrease of oxygen into the sediment. It is following during the Early Kimmeridgian by a replacement of foraminiferal assemblages. The almost all Kimmeridgian is characterized by the abundance of many common with Boreal and Subboreal Realm. Connections toward the South began again dominant after a small regressive event recorded during the Late Kimmeridgian and associated with the abundance of many common taxa with Subboreal Realm and Peritethys such as Crimea and Caucasus taxa. Foraminiferal assemblages of the East European Platform are strongly affected by palaeoecological changes and may display a very good model for biofacies typification under Boreal and Subboreal environments. The East European Platform appears to be a key area for the understanding of Upper Jurassic big scale palaeoceanographical changes, being connected with Boreal to Peritethyan basins.

Keywords: foraminifera, palaeoceanography, palaeoecology, upper jurassic

Procedia PDF Downloads 223

Authors: Sevdenur Onger, Ali Asram Sagiroglu

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Hyperpigmentation is a cosmetically unappealing skin problem caused by an overabundance of melanin in the skin. Its pathophysiology is caused by melanocytes being exposed to paracrine melanogenic stimuli, which can upregulate melanogenesis-related enzymes (such as tyrosinase) and cause melanosome formation. Tyrosinase is linked to the development of melanosomes biochemically, and it is the main target of hyperpigmentation treatment. therefore, decreasing tyrosinase activity to reduce melanosomes has become the main target of hyperpigmentation treatment. Niacinamide (NA) is a natural chemical found in a variety of plants that is used as a skin-whitening ingredient in cosmetic formulations. NA decreases melanogenesis in the skin by inhibiting melanosome transfer from melanocytes to covering keratinocytes. Furthermore, NA protects the skin from reactive oxygen species and acts as a main barrier with the skin, reducing moisture loss by increasing ceramide and fatty acid synthesis. However, it is very difficult for hydrophilic compounds such as NA to penetrate deep into the skin. Furthermore, because of the nicotinic acid in NA, it is an irritant. As a result, we've concentrated on strategies to increase NA skin permeability while avoiding its irritating impacts. Since nanotechnology can affect drug penetration behavior by controlling the release and increasing the period of permanence on the skin, it can be a useful technique in the development of whitening formulations. Liposomes have become increasingly popular in the cosmetics industry in recent years due to benefits such as their lack of toxicity, high penetration ability in living skin layers, ability to increase skin moisture by forming a thin layer on the skin surface, and suitability for large-scale production. Therefore, liposomes containing NA were developed for this study. Different formulations were prepared by varying the amount of phospholipid and cholesterol and examined in terms of particle sizes, polydispersity index (PDI) and pH values. The pH values of the produced formulations were determined to be suitable with the pH value of the skin. Particle sizes were determined to be smaller than 250 nm and the particles were found to be of homogeneous size in the formulation (pdi<0.30). Despite the important advantages of liposomal systems, they have low viscosity and stability for topical use. For these reasons, in this study, liposomal cream formulations have been prepared for easy topical application of liposomal systems. As a result, liposomal cream formulations containing NA have been successfully prepared and characterized. Following the in-vitro release and ex-vivo diffusion studies to be conducted in the continuation of the study, it is planned to test the formulation that gives the most appropriate result on the volunteers after obtaining the approval of the ethics committee.

Keywords: delivery systems, hyperpigmentation, liposome, niacinamide

Procedia PDF Downloads 97

Authors: Adewale O. Adegbenjo, Elsie Nsiah-Baafi, Mxolisi B. Shongwe, Mercy Ramakokovhu, Peter A. Olubambi

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The sintering step in powder metallurgy (P/M) processes is very sensitive as it determines to a large extent the properties of the final component produced. Spark plasma sintering over the past decade has been extensively used in consolidating a wide range of materials including metallic alloy powders. This novel, non-conventional sintering method has proven to be advantageous offering full densification of materials, high heating rates, low sintering temperatures, and short sintering cycles over conventional sintering methods. Ti6Al4V has been adjudged the most widely used α+β alloy due to its impressive mechanical performance in service environments, especially in the aerospace and automobile industries being a light metal alloy with the capacity for fuel efficiency needed in these industries. The P/M route has been a promising method for the fabrication of parts made from Ti6Al4V alloy due to its cost and material loss reductions and the ability to produce near net and intricate shapes. However, the use of this alloy has been largely limited owing to its relatively poor hardness and wear properties. The effect of sintering temperature on the densification, hardness, and wear behaviors of spark plasma sintered Ti6Al4V powders was investigated in this present study. Sintering of the alloy powders was performed in the 650–850°C temperature range at a constant heating rate, applied pressure and holding time of 100°C/min, 50 MPa and 5 min, respectively. Density measurements were carried out according to Archimedes’ principle and microhardness tests were performed on sectioned as-polished surfaces at a load of 100gf and dwell time of 15 s. Dry sliding wear tests were performed at varied sliding loads of 5, 15, 25 and 35 N using the ball-on-disc tribometer configuration with WC as the counterface material. Microstructural characterization of the sintered samples and wear tracks were carried out using SEM and EDX techniques. The density and hardness characteristics of sintered samples increased with increasing sintering temperature. Near full densification (99.6% of the theoretical density) and Vickers’ micro-indentation hardness of 360 HV were attained at 850°C. The coefficient of friction (COF) and wear depth improved significantly with increased sintering temperature under all the loading conditions examined, except at 25 N indicating better mechanical properties at high sintering temperatures. Worn surface analyses showed the wear mechanism was a synergy of adhesive and abrasive wears, although the former was prevalent.

Keywords: hardness, powder metallurgy, spark plasma sintering, wear

Procedia PDF Downloads 247

Authors: T. Garlan, I. Gabelotaud, S. Lucas, E. Marchès

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Production of a global sedimentological seabed map has been initiated in 1995 to provide the necessary tool for searches of aircraft and boats lost at sea, to give sedimentary information for nautical charts, and to provide input data for acoustic propagation modelling. This original approach had already been initiated one century ago when the French hydrographic service and the University of Nancy had produced maps of the distribution of marine sediments of the French coasts and then sediment maps of the continental shelves of Europe and North America. The current map of the sediment of oceans presented was initiated with a UNESCO's general map of the deep ocean floor. This map was adapted using a unique sediment classification to present all types of sediments: from beaches to the deep seabed and from glacial deposits to tropical sediments. In order to allow good visualization and to be adapted to the different applications, only the granularity of sediments is represented. The published seabed maps are studied, if they present an interest, the nature of the seabed is extracted from them, the sediment classification is transcribed and the resulted map is integrated in the world map. Data come also from interpretations of Multibeam Echo Sounder (MES) imagery of large hydrographic surveys of deep-ocean. These allow a very high-quality mapping of areas that until then were represented as homogeneous. The third and principal source of data comes from the integration of regional maps produced specifically for this project. These regional maps are carried out using all the bathymetric and sedimentary data of a region. This step makes it possible to produce a regional synthesis map, with the realization of generalizations in the case of over-precise data. 86 regional maps of the Atlantic Ocean, the Mediterranean Sea, and the Indian Ocean have been produced and integrated into the world sedimentary map. This work is permanent and permits a digital version every two years, with the integration of some new maps. This article describes the choices made in terms of sediment classification, the scale of source data and the zonation of the variability of the quality. This map is the final step in a system comprising the Shom Sedimentary Database, enriched by more than one million punctual and surface items of data, and four series of coastal seabed maps at 1:10,000, 1:50,000, 1:200,000 and 1:1,000,000. This step by step approach makes it possible to take into account the progresses in knowledge made in the field of seabed characterization during the last decades. Thus, the arrival of new classification systems for seafloor has improved the recent seabed maps, and the compilation of these new maps with those previously published allows a gradual enrichment of the world sedimentary map. But there is still a lot of work to enhance some regions, which are still based on data acquired more than half a century ago.

Keywords: marine sedimentology, seabed map, sediment classification, world ocean

Procedia PDF Downloads 213

Authors: Mohamed K. Khalil, Mohamed S. Ragab

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Atomizers are used in many engineering applications including diesel engines, petrol engines and spray combustion in furnaces as well as gas turbine engines. These atomizers are used to increase the specific surface area of the fuel, which achieve a high rate of fuel mixing and evaporation. In all combustion systems reduction in mean drop size is a challenge which has many advantages since it leads to rapid and easier ignition, higher volumetric heat release rate, wider burning range and lower exhaust concentrations of the pollutant emissions. Pressure atomizers have a different configuration for design such as swirl atomizer (simplex), dual orifice, spill return, plain orifice, duplex and fan spray. Simplex pressure atomizers are the most common type of all. Among all types of atomizers, pressure swirl types resemble a special category since they differ in quality of atomization, the reliability of operation, simplicity of construction and low expenditure of energy. But, the disadvantages of these atomizers are that they require very high injection pressure and have low discharge coefficient owing to the fact that the air core covers the majority of the atomizer orifice. To overcome these problems, dual orifice atomizer was designed. This paper proposes a detailed mathematical model design procedure for both pressure swirl atomizer (Simplex) and dual orifice atomizer, examines the effects of varying fuel type and makes a clear comparison between the two types. Using five types of fuel (JP-5, JA1, JP-4, Diesel and Bio-Diesel) as a case study, reveal the effect of changing fuel type and its properties on atomizers design and spray characteristics. Which effect on combustion process parameters; Sauter Mean Diameter (SMD), spray cone angle and sheet thickness with varying the discharge coefficient from 0.27 to 0.35 during takeoff for high bypass turbofan engines. The spray atomizer performance of the pressure swirl fuel injector was compared to the dual orifice fuel injector at the same differential pressure and discharge coefficient using Excel. The results are analyzed and handled to form the final reliability results for fuel injectors in high bypass turbofan engines. The results show that the Sauter Mean Diameter (SMD) in dual orifice atomizer is larger than Sauter Mean Diameter (SMD) in pressure swirl atomizer, the film thickness (h) in dual orifice atomizer is less than the film thickness (h) in pressure swirl atomizer. The Spray Cone Angle (α) in pressure swirl atomizer is larger than Spray Cone Angle (α) in dual orifice atomizer.

Keywords: gas turbine engines, atomization process, Sauter mean diameter, JP-5

Procedia PDF Downloads 146

Authors: Aprajeeta Jha, Punyadarshini P. Tripathy

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Drying technologies for various food processing operations shares an inevitable linkage with energy, cost and environmental sustainability. Hence, solar drying of food grains has become imperative choice to combat duo challenges of meeting high energy demand for drying and to address climate change scenario. But performance and reliability of solar dryers depend hugely on sunshine period, climatic conditions, therefore, offer a limited control over drying conditions and have lower efficiencies. Solar drying technology, supported by Photovoltaic (PV) power plant and hybrid type solar air collector can potentially overpower the disadvantages of solar dryers. For development of such robust hybrid dryers; to ensure quality and shelf-life of paddy grains the optimization of process parameter becomes extremely critical. Investigation of the moisture distribution profile within the grains becomes necessary in order to avoid over drying or under drying of food grains in hybrid solar dryer. Computational simulations based on finite element modeling can serve as potential tool in providing a better insight of moisture migration during drying process. Hence, present work aims at optimizing the process parameters and to develop a 3-dimensional (3D) finite element model (FEM) for predicting moisture profile in paddy during solar drying. COMSOL Multiphysics was employed to develop a 3D finite element model for predicting moisture profile. Furthermore, optimization of process parameters (power level, air velocity and moisture content) was done using response surface methodology in design expert software. 3D finite element model (FEM) for predicting moisture migration in single kernel for every time step has been developed and validated with experimental data. The mean absolute error (MAE), mean relative error (MRE) and standard error (SE) were found to be 0.003, 0.0531 and 0.0007, respectively, indicating close agreement of model with experimental results. Furthermore, optimized process parameters for drying paddy were found to be 700 W, 2.75 m/s at 13% (wb) with optimum temperature, milling yield and drying time of 42˚C, 62%, 86 min respectively, having desirability of 0.905. Above optimized conditions can be successfully used to dry paddy in PV integrated solar dryer in order to attain maximum uniformity, quality and yield of product. PV-integrated hybrid solar dryers can be employed as potential and cutting edge drying technology alternative for sustainable energy and food security.

Keywords: finite element modeling, moisture migration, paddy grain, process optimization, PV integrated hybrid solar dryer

Procedia PDF Downloads 126

Authors: Rosie Cooper, Tracey Chantler, Ellen Pringle, Sadie Bell, Emily Edmundson, Heidi Nielsen, Sheila Roberts, Michael Edelstein, Sandra Mounier Jack

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Introduction: In line with the National Health Service’s (NHS) long-term plan, the NHS is looking to implement more digital health interventions. This study explores a case study in this area: a digital intervention used by NHS Trusts in London to consent adolescents for Human Papilloma Virus (HPV) immunisation. Methods: The electronic consent intervention was implemented in 14 secondary schools in inner city, London. These schools were statistically matched with 14 schools from the same area that were consenting using paper forms. Schools were matched on deprivation and English as an additional language. Consent form return rates and HPV vaccine uptake were compared quantitatively between intervention and matched schools. Data from observations of immunisation sessions and school feedback forms were analysed thematically. Individual and group interviews were undertaken with implementers parents and adolescents and a focus group with adolescents were undertaken and analysed thematically. Results: Twenty-eight schools (14 e-consent schools and 14 paper consent schools) comprising 3219 girls (1733 in paper consent schools and 1486 in e-consent schools) were included in the study. The proportion of pupils eligible for free school meals, with English as an additional language and students' ethnicity profile, was similar between the e-consent and paper consent schools. Return of consent forms was not increased by the implementation of the e-consent intervention. There was no difference in the proportion of pupils that were vaccinated at the scheduled vaccination session between the paper (n=14) and e-consent (n=14) schools (80.6% vs. 81.3%, p=0.93). The transition to using the system was not straightforward, whilst schools and staff understood the potential benefits, they found it difficult to adapt to new ways of working which removed some level or control from schools. Part of the reason for lower consent form return in e-consent schools was that some parents found the intervention difficult to use due to limited access to the internet, finding it hard to open the weblink, language barriers, and in some cases, the system closed a few days prior to sessions. Adolescents also highlighted the potential for e-consent interventions to by-pass their information needs. Discussion: We would advise caution against dismissing the e-consent intervention because it did not achieve its goal of increasing the return of consent forms. Given the problems embedding a news service, it was encouraging that HPV vaccine uptake remained stable. Introducing change requires stakeholders to understand, buy in, and work together with others. Schools and staff understood the potential benefits of using e-consent but found the new ways of working removed some level of control from schools, which they found hard to adapt to, possibly suggesting implementing digital technology will require an embedding process. Conclusion: The future direction of the NHS will require implementation of digital technology. Obtaining electronic consent from parents could help streamline school-based adolescent immunisation programmes. Findings from this study suggest that when implementing new digital technologies, it is important to allow for a period of embedding to enable them to become incorporated in everyday practice.

Keywords: consent, digital, immunisation, prevention

Procedia PDF Downloads 118

Authors: A. T. Perez Fontenla, S. Sgobba, A. Bartkowska, Y. Askar, M. Dalemir Celuch, A. Newborough, M. Karppinen, H. Haalien, S. Deleval, S. Larcher, C. Charvet, L. Bruno, R. Trant

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The present study investigates the corrosion behavior of copper (Cu) based conducts predominantly brazed with Sil-Fos (self-fluxing copper-based filler with silver and phosphorus) within various cooling circuits of demineralized water across different particle accelerator components at CERN. The study covers a range of sample service time, from a few months to fifty years, and includes various accelerator components such as quadrupoles, dipoles, and bending magnets. The investigation comprises the established sample extraction procedure, examination methodology including non-destructive testing, evaluation of the corrosion phenomena, and identification of commonalities across the studied components as well as analysis of the environmental influence. The systematic analysis included computed microtomography (CT) of the joints that revealed distributed defects across all brazing interfaces. Some defects appeared to result from areas not wetted by the filler during the brazing operation, displaying round shapes, while others exhibited irregular contours and radial alignment, indicative of a network or interconnection. The subsequent dry cutting performed facilitated access to the conduct's inner surface and the brazed joints for further inspection through light and electron microscopy (SEM) and chemical analysis via Energy Dispersive X-ray spectroscopy (EDS). Brazing analysis away from affected areas identified the expected phases for a Sil-Fos alloy. In contrast, the affected locations displayed micrometric cavities propagating into the material, along with selective corrosion of the bulk Cu initiated at the conductor-braze interface. Corrosion product analysis highlighted the consistent presence of sulfur (up to 6 % in weight), whose origin and role in the corrosion initiation and extension is being further investigated. The importance of this study is paramount as it plays a crucial role in comprehending the underlying factors contributing to recently identified water leaks and evaluating the extent of the issue. Its primary objective is to provide essential insights for the repair of impacted brazed joints when accessibility permits. Moreover, the study seeks to contribute to the improvement of design and manufacturing practices for future components, ultimately enhancing the overall reliability and performance of magnet systems within CERN accelerator facilities.

Keywords: accelerator facilities, brazed copper conducts, demineralized water, magnets

Procedia PDF Downloads 28

Authors: Monika Dmitrzak-Weglarz, Aleksandra Rajewska-Rager, Maria Skibinska, Natalia Lepczynska, Piotr Sibilski, Joanna Pawlak, Pawel Kapelski, Joanna Hauser

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Epidermal growth factor (EGF) is a well-known neurotrophic factor that involves in neuronal growth and synaptic plasticity. The proteomic research provided in order to identify novel candidate biological markers for mood disorders focused on elevated EGF serum level in patients during depression episode. However, the EGF association with mood disorder spectrum among adolescents and young adults has not been studied extensively. In this study, we aim to investigate the serum levels of EGF in adolescents and young adults during hypo/manic, depressive episodes and in remission compared to healthy control group. In our study, we involved 80 patients aged 12-24 years in 2-year follow-up study with a primary diagnosis of mood disorder spectrum, and 35 healthy volunteers matched by age and gender. Diagnoses were established according to DSM-IV-TR criteria using structured clinical interviews: K-SADS for child and adolescents, and SCID for young adults. Clinical and biological evaluations were made at baseline and euthymic mood (at 3th or 6th month of treatment and after 1 and 2 years). The Young Mania Rating Scale and Hamilton Rating Scale for Depression were used for assessment. The study protocols were approved by the relevant ethics committee. Serum protein concentration was determined by Enzyme-Linked Immunosorbent Assays (ELISA) method. Human EGF (cat. no DY 236) DuoSet ELISA kit was used (R&D Systems). Serum EGF levels were analysed with following variables: age, age under 18 and above 18 years old, sex, family history of affective disorders, drug-free vs. medicated. Shapiro-Wilk test was used to test the normality of the data. The homogeneity of variance was calculated with Levene’s test. EGF levels showed non-normal distribution and the homogeneity of variance was violated. Non-parametric tests: Mann-Whitney U test, Kruskall-Wallis ANOVA, Friedman’s ANOVA, Wilcoxon signed rank test, Spearman correlation coefficient was applied in the analyses The statistical significance level was set at p<0.05. Elevated EGF level at baseline (p=0.001) and at month 24 (p=0.02) was detected in study subjects compared with controls. Increased EGF level in women at month 12 (p=0.02) compared to men in study group have been observed. Using Wilcoxon signed rank test differences in EGF levels were detected: decrease from baseline to month 3 (p=0.014) and increase comparing: month 3 vs. 24 (p=0.013); month 6 vs. 12 (p=0.021) and vs. 24 (p=0.008). EGF level at baseline was negatively correlated with depression and mania occurrence at 24 months. EGF level at 24 months was positively correlated with depression and mania occurrence at 12 months. No other correlations of EGF levels with clinical and demographical variables have been detected. The findings of the present study indicate that EGF serum level is significantly elevated in the study group of patients compared to the controls. We also observed fluctuations in EGF levels during two years of disease observation. EGF seems to be useful as an early marker for prediction of diagnosis, course of illness and treatment response in young patients during first episode od mood disorders, which requires further investigation. Grant was founded by National Science Center in Poland no 2011/03/D/NZ5/06146.

Keywords: biological marker, epidermal growth factor, mood disorders, prediction

Procedia PDF Downloads 167

Authors: Nafisa Mahbub, Hajo Ribberink

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Electrification of long-haul trucks has been in discussion as a potential strategy to decarbonization. These trucks will require large batteries because of their weight and long daily driving distances. Around 245 million battery electric vehicles are predicted to be on the road by the year 2035. This huge increase in the number of electric vehicles (EVs) will require intensive mining operations for metals and other materials to manufacture millions of batteries for the EVs. These operations will add significant environmental burdens and there is a significant risk that the mining sector will not be able to meet the demand for battery materials, leading to higher prices. Since the battery is the most expensive component in the EVs, technologies that can enable electrification with smaller batteries sizes have substantial potential to reduce the material usage and associated environmental and cost burdens. One of these technologies is an ‘electrified road’ (eroad), where vehicles receive power while they are driving, for instance through an overhead catenary (OC) wire (like trolleybuses and electric trains), through wireless (inductive) chargers embedded in the road, or by connecting to an electrified rail in or on the road surface. This study assessed the total material use and associated life cycle GHG emissions of two types of eroads (overhead catenary and in-road wireless charging) for long-haul trucks in Canada and compared them to electrification using stationary plug-in fast charging. As different electrification technologies require different amounts of materials for charging infrastructure and for the truck batteries, the study included the contributions of both for the total material use. The study developed a bottom-up approach model comparing the three different charging scenarios – plug in fast chargers, overhead catenary and in-road wireless charging. The investigated materials for charging technology and batteries were copper (Cu), steel (Fe), aluminium (Al), and lithium (Li). For the plug-in fast charging technology, different charging scenarios ranging from overnight charging (350 kW) to megawatt (MW) charging (2 MW) were investigated. A 500 km of highway (1 lane of in-road charging per direction) was considered to estimate the material use for the overhead catenary and inductive charging technologies. The study considered trucks needing an 800 kWh battery under the plug-in charger scenario but only a 200 kWh battery for the OC and inductive charging scenarios. Results showed that overall the inductive charging scenario has the lowest material use followed by OC and plug-in charger scenarios respectively. The materials use for the OC and plug-in charger scenarios were 50-70% higher than for the inductive charging scenarios for the overall system including the charging infrastructure and battery. The life cycle GHG emissions from the construction and installation of the charging technology material were also investigated.

Keywords: charging technology, eroad, GHG emissions, material use, overhead catenary, plug in charger

Procedia PDF Downloads 32

Authors: Bistra Kunovska, Kremena Ivanova, Jana Djounova, Desislava Djunakova, Zdenka Stojanovska

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The carcinogenic effects of radon as a radioactive noble gas have been studied and show a strong correlation between radon exposure and lung cancer occurrence, even in the case of low radon levels. The major part of the natural radiation dose in humans is received by inhaling radon and its progenies, which originates from the decay chain of U-238. Indoor radon poses a substantial threat to human health when build-up occurs in confined spaces such as homes, mines and caves and the risk increases with the duration of radon exposure and is proportional to both the radon concentration and the time of exposure. Tourist caves are a case of special environmental conditions that may be affected by high radon concentration. Tourist caves are a recognized danger in terms of radon exposure to cave workers (guides, employees working in shops built above the cave entrances, etc.), but due to the sensitive nature of the cave environment, high concentrations cannot be easily removed. Forced ventilation of the air in the caves is considered unthinkable due to the possible harmful effects on the microclimate, flora and fauna. The risks to human health posed by exposure to elevated radon levels in caves are not well documented. Various studies around the world often detail very high concentrations of radon in caves and exposure of employees but without a follow-up assessment of the overall impact on human health. This study was developed in the implementation of a national project to assess the potential health effects caused by exposure to elevated levels of radon in buildings with public access under the National Science Fund of Bulgaria, in the framework of grant No КП-06-Н23/1/07.12.2018. The purpose of the work is to assess the radon level in Bulgarian caves and the exposure of the visitors and workers. The number of caves (sampling size) was calculated for simple random selection from total available caves 65 (sampling population) are 13 caves with confidence level 95 % and confidence interval (margin of error) approximately 25 %. A measurement of the radon concentration in air at specific locations in caves was done by using CR-39 type nuclear track-etch detectors that were placed by the participants in the research team. Despite the fact that all of the caves were formed in karst rocks, the radon levels were rather different from each other (97–7575 Bq/m3). An assessment of the influence of the orientation of the caves in the earth's surface (horizontal, inclined, vertical) on the radon concentration was performed. Evaluation of health hazards and radon risk exposure causing by inhaling the radon and its daughter products in each surveyed caves was done. Reducing the time spent in the cave has been recommended in order to decrease the exposure of workers.

Keywords: tourist caves, radon concentration, exposure, Bulgaria

Procedia PDF Downloads 167

Authors: Chau-Kuang Chen, Juanita Buford, Colette Davis, Raisha Allen, John Hughes, James Tyus, Dexter Samuels

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During the post-Civil War era, the city of Nashville, Tennessee, had the highest mortality rate in the country. The elevated death and disease among ex-slaves were attributable to the unavailability of healthcare. To address the paucity of healthcare services, the College, an institution with the mission of educating minority professionals and serving the under served population, was established in 1876. This study was designed to assess if the College has accomplished its mission of serving under served communities and contributed to the elimination of health disparities in the United States. The study objective was to quantify the impact of socioeconomic status and adverse health outcomes on primary care professionals serving disadvantaged communities, which, in turn, was significantly associated with a health professional shortage score partly designated by the U.S. Department of Health and Human Services. Various statistical methods were used to analyze the alumni data in years 1975 – 2013. K-means cluster analysis was utilized to identify individual medical and dental graduates into the cluster groups of the practice communities (Disadvantaged or Non-disadvantaged Communities). Discriminant analysis was implemented to verify the classification accuracy of cluster analysis. The independent t test was performed to detect the significant mean differences for clustering and criterion variables between Disadvantaged and Non-disadvantaged Communities, which confirms the “content” validity of cluster analysis model. Chi-square test was used to assess if the proportion of cluster groups (Disadvantaged vs Non-disadvantaged Communities) were consistent with that of practicing specialties (primary care vs. non-primary care). Finally, the partial least squares (PLS) path model was constructed to explore the “construct” validity of analytics model by providing the magnitude effects of socioeconomic status and adverse health outcome on primary care professionals serving disadvantaged community. The social ecological theory along with statistical models mentioned was used to establish the relationship between medical and dental graduates (primary care professionals serving disadvantaged communities) and their social environments (socioeconomic status, adverse health outcome, health professional shortage score). Based on social ecological framework, it was hypothesized that the impact of socioeconomic status and adverse health outcomes on primary care professionals serving disadvantaged communities could be quantified. Also, primary care professionals serving disadvantaged communities related to a health professional shortage score can be measured. Adverse health outcome (adult obesity rate, age-adjusted premature mortality rate, and percent of people diagnosed with diabetes) could be affected by the latent variable, namely socioeconomic status (unemployment rate, poverty rate, percent of children who were in free lunch programs, and percent of uninsured adults). The study results indicated that approximately 83% (3,192/3,864) of the College’s medical and dental graduates from 1975 to 2013 were practicing in disadvantaged communities. In addition, the PLS path modeling demonstrated that primary care professionals serving disadvantaged community was significantly associated with socioeconomic status and adverse health outcome (p < .001). In summary, the majority of medical and dental graduates from the College provide primary care services to disadvantaged communities with low socioeconomic status and high adverse health outcomes, which demonstrate that the College has fulfilled its mission.

Keywords: disadvantaged community, K-means cluster analysis, PLS path modeling, primary care

Procedia PDF Downloads 534

Authors: G. Bravo, D. Lopez, A. Iriarte

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Several organizations and governments have created a demand for information about the environmental impacts of agricultural products. Today, the export oriented fruit sector in Chile is being challenged to quantify and reduce their environmental impacts. Chile is the largest southern hemisphere producer and exporter of sweet cherry fruit. Chilean sweet cherry production reached a volume of 80,000 tons in 2012. The main destination market for the Chilean cherry in 2012 was Asia (including Hong Kong and China), taking in 69% of exported volume. Another important market was the United States with 16% participation, followed by Latin America (7%) and Europe (6%). Concerning geographical distribution, the Chilean conventional cherry production is focused in the center-south area, between the regions of Maule and O’Higgins; both regions represent 81% of the planted surface. The Life Cycle Assessment (LCA) is widely accepted as one of the major methodologies for assessing environmental impacts of products or services. The LCA identifies the material, energy, material, and waste flows of a product or service, and their impact on the environment. There are scant studies that examine the impacts of sweet cherry cultivation, such as acidification and eutrophication. Within this context, the main objective of this study is to evaluate, using the LCA, the acidification and eutrophication impacts of sweet cherry production in Chile. The additional objective is to identify the agricultural inputs that contributed significantly to the impacts of this fruit. The system under study included all the life cycle stages from the cradle to the farm gate (harvested sweet cherry). The data of sweet cherry production correspond to nationwide representative practices and are based on technical-economic studies and field information obtained in several face-to-face interviews. The study takes into account the following agricultural inputs: fertilizers, pesticides, diesel consumption for agricultural operations, machinery and electricity for irrigation. The results indicated that the mineral fertilizers are the most important contributors to the acidification and eutrophication impacts of the sheet cherry cultivation. Improvement options are suggested for the hotspot in order to reduce the environmental impacts. The results allow planning and promoting low impacts procedures across fruit companies, as well as policymakers, and other stakeholders on the subject. In this context, this study is one of the first assessments of the environmental impacts of sweet cherry production. New field data or evaluation of other life cycle stages could further improve the knowledge on the impacts of this fruit. This study may contribute to environmental information in other countries where there is similar agricultural production for sweet cherry.

Keywords: acidification, eutrophication, life cycle assessment, sweet cherry production

Procedia PDF Downloads 252

Authors: Farwa Rizvi, Joanne Williams, Humaira Maheen, Elizabeth Hoban

Abstract:

There is an increase in risky sexual behavior and unsafe sex in adolescent girls and young women aged 15 to 24 years in Cambodia, which negatively affects their reproductive health by increasing the risk of contracting sexually transmitted infections and unintended pregnancies. Risky sexual behavior includes ‘having sex at an early age, having multiple sexual partners, having sex while under the influence of alcohol or drugs, and unprotected sexual behaviors’. A systematic review of quantitative research conducted in Cambodia was undertaken, using the theoretical framework of the Social Ecological Model to identify the personal, social and cultural factors associated with risky sexual behavior and unsafe sex in young Cambodian women. PRISMA guidelines were used to search databases including Medline Complete, PsycINFO, CINAHL Complete, Academic Search Complete, Global Health, and Social Work Abstracts. Additional searches were conducted in Science Direct, Google Scholar and in the grey literature sources. A risk-of-bias tool developed explicitly for the systematic review of cross-sectional studies was used. Summary item on the overall risk of study bias after the inter-rater response showed that the risk-of-bias was high in two studies, moderate in one study and low in one study. The search strategy included a combination of subject terms and free text terms. The medical subject headings (MeSH) terms included were; contracept* or ‘birth control’ or ‘family planning’ or pregnan* or ‘safe sex’ or ‘protected intercourse’ or ‘unprotected intercourse’ or ‘protected sex’ or ‘unprotected sex’ or ‘risky sexual behaviour*’ or ‘abort*’ or ‘planned parenthood’ or ‘unplanned pregnancy’ AND ( barrier* or obstacle* or challenge* or knowledge or attitude* or factor* or determinant* or choic* or uptake or discontinu* or acceptance or satisfaction or ‘needs assessment’ or ‘non-use’ or ‘unmet need’ or ‘decision making’ ) AND Cambodia*. Initially, 300 studies were identified by using key words and finally, four quantitative studies were selected based on the inclusion criteria. The four studies were published between 2010 and 2016. The study participants ranged in age from 10-24 years, single or married, with 3 to 10 completed years of education. The mean age at sexual debut was reported to be 18 years. Using the perspective of the Social Ecological Model, risky sexual behavior was associated with individual-level factors including young age at sexual debut, low education, unsafe sex under the influence of alcohol and substance abuse, multiple sexual partners or transactional sex. Family level factors included living away from parents, orphan status and low levels of family support. Peer and partner level factors included peer delinquency and lack of condom use. Low socioeconomic status at the society level was also associated with risky sexual behaviour. There is scant research on sexual and reproductive health of adolescent girls and young women in Cambodia. Individual, family and social factors were significantly associated with risky sexual behaviour. More research is required to inform potential preventive strategies and policies that address young women’s sexual and reproductive health.

Keywords: adolescents, high-risk sex, sexual activity, unplanned pregnancies

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Authors: Zhe Li, Tao Ju, Liguo Zhang, Zehong Zhang, Baoshun Zhang

Abstract:

In-grow stacking-faults (IGSFs) in 4H-SiC epilayers can cause increased leakage current and reduce the blocking voltage of 4H-SiC power devices. Double Shockley stacking fault (2SSF) is a common type of IGSF with double slips on the basal planes. In this study, a 2SSF in the 4H-SiC epilayer grown by chemical vaper deposition (CVD) is characterized. The nucleation site of the 2SSF is discussed, and a model for the 2SSF nucleation is proposed. Homo-epitaxial 4H-SiC is grown on a commercial 4 degrees off-cut substrate by a home-built hot-wall CVD. Defect-selected-etching (DSE) is conducted with melted KOH at 500 degrees Celsius for 1-2 min. Room temperature cathodoluminescence (CL) is conducted at a 20 kV acceleration voltage. Low-temperature photoluminescence (LTPL) is conducted at 3.6 K with the 325 nm He-Cd laser line. In the CL image, a triangular area with bright contrast is observed. Two partial dislocations (PDs) with a 20-degree angle in between show linear dark contrast on the edges of the IGSF. CL and LTPL spectrums are conducted to verify the IGSF’s type. The CL spectrum shows the maximum photoemission at 2.431 eV and negligible bandgap emission. In the LTPL spectrum, four phonon replicas are found at 2.468 eV, 2.438 eV, 2.420 eV and 2.410 eV, respectively. The Egx is estimated to be 2.512 eV. A shoulder with a red-shift to the main peak in CL, and a slight protrude at the same wavelength in LTPL are verified as the so called Egx- lines. Based on the CL and LTPL results, the IGSF is identified as a 2SSF. Back etching by neutral loop discharge and DSE are conducted to track the origin of the 2SSF, and the nucleation site is found to be a threading screw dislocation (TSD) in this sample. A nucleation mechanism model is proposed for the formation of the 2SSF. Steps introduced by the off-cut and the TSD on the surface are both suggested to be two C-Si bilayers height. The intersections of such two types of steps are along [11-20] direction from the TSD, while a four-bilayer step at each intersection. The nucleation of the 2SSF in the growth is proposed as follows. Firstly, the upper two bilayers of the four-bilayer step grow down and block the lower two at one intersection, and an IGSF is generated. Secondly, the step-flow grows over the IGSF successively, and forms an AC/ABCABC/BA/BC stacking sequence. Then a 2SSF is formed and extends by the step-flow growth. In conclusion, a triangular IGSF is characterized by CL approach. Base on the CL and LTPL spectrums, the estimated Egx is 2.512 eV and the IGSF is identified to be a 2SSF. By back etching, the 2SSF nucleation site is found to be a TSD. A model for the 2SSF nucleation from an intersection of off-cut- and TSD- introduced steps is proposed.

Keywords: cathodoluminescence, defect-selected-etching, double Shockley stacking fault, low-temperature photoluminescence, nucleation model, silicon carbide

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Authors: Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Kogieleum Naidoo, Helen McIlleron, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Nesri Padayatachi

Abstract:

Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation.

Keywords: rifampicin, isoniazid pharmacokinetics, genetics, NAT2, SLCO1B1, tuberculosis

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Authors: H. Jamili, S. Shakiba

Abstract:

Today, one of the main concerns of human beings is facing the unpleasant changes of the environment. Buildings are responsible for a significant amount of natural resources consumption and carbon emissions production. In such a situation, this thought comes to mind that changing each building into a phenomenon of benefit to the environment. A change in a way that each building functions as an element that supports the environment, and construction, in addition to answering the need of humans, is encouraged, the way planting a tree is, and it is no longer seen as a threat to alive beings and the planet. Prospect: Today, different ideas of developing materials that can smartly function are realizing. For instance, Programmable Materials, which in different conditions, can respond appropriately to the situation and have features of modification in shape, size, physical properties and restoration, and repair quality. Studies are to progress having this purpose to plan for these materials in a way that they are easily available, and to meet this aim, there is no need to use expensive materials and high technologies. In these cases, physical attributes of materials undertake the role of sensors, wires and actuators then materials will become into robots itself. In fact, we experience robotics without robots. In recent decades, AI and technology advances have dramatically improving the performance of materials. These achievements are a combination of software optimizations and physical productions such as multi-materials 3D printing. These capabilities enable us to program materials in order to change shape, appearance, and physical properties to interact with different situations. nIt is expected that further achievements like Memory Materials and Self-learning Materials are also added to the Smart Materials family, which are affordable, available, and of use for a variety of applications and industries. From the architectural standpoint, the building skin is significantly considered in this research, concerning the noticeable surface area the buildings skin have in urban space. The purpose of this research would be finding a way that the programmable materials be used in building skin with the aim of having an effective and positive interaction. A Pixel Façade would be a solution for programming a building skin. The Pixel Facadeincludes components that contain a series of attributes that help buildings for their needs upon their environmental criteria. A PIXEL contains series of smart materials and digital controllers together. It not only benefits its physical properties, such as control the amount of sunlight and heat, but it enhances building performance by providing a list of features, depending on situation criteria. The features will vary depending on locations and have a different function during the daytime and different seasons. The primary role of a PIXEL FAÇADE can be defined as filtering pollutions (for inside and outside of the buildings) and providing clean energy as well as interacting with other PIXEL FACADES to estimate better reactions.

Keywords: building skin, environmental crisis, pixel facade, programmable materials, smart materials

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Authors: Iulianna Taritsa, Kuldeep Neote, Eric Fossel

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Lysosome-induced immunogenic cell death (LIICD) is a powerful mechanism of targeting cancer cells that kills circulating malignant cells and primes the host’s immune cells against future remission. Current immunotherapies for cancer are limited in preventing recurrence – a gap that can be bridged by training the immune system to recognize cancer neoantigens. Lysosomal leakage can be induced therapeutically to traffic antigens from dying cells to dendritic cells, which can later present those tumorigenic antigens to T cells. Previous research has shown that oxidative agents administered in the tumor microenvironment can initiate LIICD. We generated a fusion protein between an oxidative agent known as xanthine oxidase (XO) and a mini-antibody specific for EGFR/HER2-sensitive breast tumor cells. The anti-EGFR single domain antibody fragment is uniquely sourced from llama, which is functional without the presence of a light chain. These llama micro-antibodies have been shown to be better able to penetrate tissues and have improved physicochemical stability as compared to traditional monoclonal antibodies. We demonstrate that the fusion protein created is stable and can induce early markers of immunogenic cell death in an in vitro human breast cancer cell line (SkBr3). Specifically, we measured overall cell death, as well as surface-expressed calreticulin, extracellular ATP release, and HMGB1 production. These markers are consensus indicators of ICD. Flow cytometry, luminescence assays, and ELISA were used respectively to quantify biomarker levels between treated versus untreated cells. We also included a positive control group of SkBr3 cells dosed with doxorubicin (a known inducer of LIICD) and a negative control dosed with cisplatin (a known inducer of cell death, but not of the immunogenic variety). We looked at each marker at various time points after cancer cells were treated with the XO/antibody fusion protein, doxorubicin, and cisplatin. Upregulated biomarkers after treatment with the fusion protein indicate an immunogenic response. We thus show the potential for this fusion protein to induce an anticancer effect paired with an adaptive immune response against EGFR/HER2+ cells. Our research in human cell lines here provides evidence for the success of the same therapeutic method for patients and serves as the gateway to developing a new treatment approach against breast cancer.

Keywords: apoptosis, breast cancer, immunogenic cell death, lysosome

Procedia PDF Downloads 182