Search results for: dose calculation

Authors: Adnan Bekhit, Eskedar Lodebo, Ariaya Hymete, Hanan Ragab, Alaa El-Din Bekhit

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Malaria and leishmaniasis have emerged as serious universal health problems throughout history of mankind. According to the WHO 2008 malarial report, half of the world population is at risk of malarial infection with an estimate of 1 million deaths occurring annually mainly in the African region. Furthermore, 12-15 million people are infected with Leishmaniasis worldwide. Despite the continuous introduction of a large number of agents for the treatment of malaria, there is still unmet medical needs due to the emergence of resistance. Resistance has occurred for almost all therapeutic agents approved for the treatment of malaria. Accordingly, it was the aim of this work to design and synthesis a group of antimalarial-antileshmanial agents that would show inhibitory activity against chloroquine-resistant strain of Plasmodium falciparum. The synthesized compounds were designed to contain a pyrazolylpyrazoline moiety having an aromatic group (p-tolyl or p-chlorophenyl) at N1-position of one pyrazoline ring due to the reports of promising activities of such compounds. A formyl or acyl substituent was introduced at the N1-position of the other pyrazoline ring, to investigate the effect of bulkiness of acyl substituents at this position. The synthesized compounds were evaluated for their in-vivo antimalarial activity against Plasmodium berghei infected mice at dose levels of 20 and 30 mg/Kg. the two most active compounds were evaluated for their antimalarial activity against chloroquin-resistant strain (RKL9) of Plasmodium falciparum. In addition, the synthesized compounds were tested for their in-vitro antileshmanial activity against Leishmania aethiopica promastigotes and amastigotes. For both antimalarial and antileishmanial activities, compounds having an N1-p-tolyl group at the first pyrazoline ring did not require bulkiness at the second pyrazoline ring nitrogen where the compound bearing an acetyl group proved to be the most active of the whole series. On the other hand, bulkiness at the N1-position of the second pyazoline ring was necessary in case of compounds carrying the p-chlorophenyl group, where the two derivatives having an N1-butanoyl and an N1-benzoyl moieties at the second pyrazoline showed the best activity. Furthermore, the toxicity of the active compounds were tested and were proved to be non-toxic at 125, 250 and 500 mg/Kg. In addition, docking of the most active compound (having a p-tolyl group at the first pyrazoline-N and an acetyl moiety on the other pyrazoline-N) was performed against dihydrofolate reductase enzyme.

Keywords: pyrazoline derivatives, in-vivo antimalarial activity, docking, dihydrofolate reductase

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Authors: Choon Seong Ng, P. Petrick, C. L. Lau

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Background: Carbapenem-resistant isolates have been increasingly reported recently. Carbapenem stewardship is designed to optimize its usage particularly among medical wards with high prevalence of carbapenem prescriptions to combat such emerging resistance. Carbapenem stewardship programmes (CSP) can reduce antibiotic use but clinical outcome of such measures needs further evaluation. We examined this in a prospective manner using feedback mechanism. Methods: Our single-center prospective cohort study involved all carbapenem prescriptions across the medical wards (including medical patients admitted to intensive care unit) in a tertiary university hospital setting. The impact of such stewardship was analysed according to the accepted and the rejected groups. The primary endpoint was safety. Safety measure applied in this study was the death at 1 month. Secondary endpoints included length of hospitalisation and readmission. Results: Over the 19 months’ period, input from 144 carbapenem prescriptions was analysed on the basis of acceptance of our CSP recommendations on the use of carbapenems. Recommendations made were as follows : de-escalation of carbapenem; stopping the carbapenem; use for a short duration of 5-7 days; required prolonged duration in the case of carbapenem-sensitive Extended Spectrum Beta-Lactamases bacteremia; dose adjustment; and surgical intervention for removal of septic foci. De-escalation, shorten duration of carbapenem and carbapenem cessation comprised 79% of the recommendations. Acceptance rate was 57%. Those who accepted CSP recommendations had no increase in mortality (p = 0.92), had a shorter length of hospital stay (LOS) and had cost-saving. Infection-related deaths were found to be higher among those in the rejected group. Moreover, three rejected cases (6%) among all non-indicated cases (n = 50) were found to have developed carbapenem-resistant isolates. Lastly, Pitt’s bacteremia score appeared to be a key element affecting the carbapenem prescription’s behaviour in this trial. Conclusions: Carbapenem stewardship program in the medical wards not only saves money, but most importantly it is safe and does not harm the patients with added benefits of reducing the length of hospital stay. However, more time is needed to engage the primary clinical teams by formal clinical presentation and immediate personal feedback by senior Infectious Disease (ID) personnel to increase its acceptance.

Keywords: audit and feedback, carbapenem stewardship, medical wards, university hospital

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Authors: Virag Vass, Ilona Bereczki, Erzsebet Szabo, Nora Debreczeni, Aniko Borbas, Pal Herczegh, Arpad Tosaki

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Hydrogen sulfide (H₂S) is a toxic gas, but it is produced by certain tissues in a small quantity. According to earlier studies, ibuprofen and H₂S has a protective effect against damaging heart tissue caused by ischemia-reperfusion. Recently, we have been investigating the effect of a new water-soluble H₂S releasing ibuprofen molecule administered after artificially generated ischemia-reperfusion on isolated rat hearts. The H₂S releasing property of the new ibuprofen derivative was investigated in vitro in medium derived from heart endothelial cell isolation at two concentrations. The ex vivo examinations were carried out on rat hearts. Rats were anesthetized with an intraperitoneal injection of ketamine, xylazine, and heparin. After thoracotomy, hearts were excised and placed into ice-cold perfusion buffer. Perfusion of hearts was conducted in Langendorff mode via the cannulated aorta. In our experiments, we studied the dose-effect of the H₂S releasing molecule in Langendorff-perfused hearts with the application of gradually increasing concentration of the compound (0- 20 µM). The H₂S releasing ibuprofen derivative was applied before the ischemia for 10 minutes. H₂S concentration was measured with an H₂S detecting electrochemical sensor from the coronary effluent solution. The 10 µM concentration was chosen for further experiments when the treatment with this solution was occurred after the ischemia. The release of H₂S is occurred by the hydrolyzing enzymes that are present in the heart endothelial cells. The protective effect of the new H₂S releasing ibuprofen molecule can be confirmed by the infarct sizes of hearts using the Triphenyl-tetrazolium chloride (TTC) staining method. Furthermore, we aimed to define the effect of the H₂S releasing ibuprofen derivative on autophagic and apoptotic processes in damaged hearts after investigating the molecular markers of these events by western blotting and immunohistochemistry techniques. Our further studies will include the examination of LC3I/II, p62, Beclin1, caspase-3, and other apoptotic molecules. We hope that confirming the protective effect of new H₂S releasing ibuprofen molecule will open a new possibility for the development of more effective cardioprotective agents with exerting fewer side effects. Acknowledgment: This study was supported by the grants of NKFIH- K-124719 and the European Union and the State of Hungary co- financed by the European Social Fund in the framework of GINOP- 2.3.2-15-2016-00043.

Keywords: autophagy, hydrogen sulfide, ibuprofen, ischemia, reperfusion

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Authors: Olumuyiwa Olusola Falowo

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One of the objectives of the Millennium Development Goals is to have sustainable access to safe drinking water and basic sanitation. In line with this objective, an assessment of groundwater quality was carried out in Odigbo Local Government Area of Ondo State in November – February, 2019 to assess the drinking, domestic and irrigation uses of the water. Samples from 30 randomly selected ground water sources; 16 shallow wells and 14 from boreholes and analyzed using American Public Health Association method for the examination of water and wastewater. Water quality index calculation, and diagrams such as Piper diagram, Gibbs diagram and Wilcox diagram have been used to assess the groundwater in conjunction with irrigation indices such as % sodium, sodium absorption ratio, permeability index, magnesium ratio, Kelly ratio, and electrical conductivity. In addition statistical Principal component analysis were used to determine the homogeneity and source(s) influencing the chemistry of the groundwater. The results show that all the parameters are within the permissible limit of World Health Organization. The physico-chemical analysis of groundwater samples indicates that the dominant major cations are in decreasing order of Na+, Ca2+, Mg2+, K+ and the dominant anions are HCO-3, Cl-, SO-24, NO-3. The values of water quality index varies suggest a Good water (WQI of 50-75) accounts for 70% of the study area. The dominant groundwater facies revealed in this study are the non-carbonate alkali (primary salinity) exceeds 50% (zone 7); and transition zone with no one cation-anion pair exceeds 50% (zone 9), while evaporation; rock–water interaction, and precipitation; and silicate weathering process are the dominant processes in the hydrogeochemical evolution of the groundwater. The study indicates that waters were found within the permissible limits of irrigation indices adopted, and plot on excellent category on Wilcox plot. In conclusion, the water in the study area are good/suitable for drinking, domestic and irrigation purposes with low equivalent salinity concentrate and moderate electrical conductivity.

Keywords: equivalent salinity concentration, groundwater quality, hydrochemical facies, principal component analysis, water-rock interaction

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Authors: Sourabh Jain, Parul Madan

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Traffic noise pollution has become a challenging problem for all metro cities of India due to rapid urbanization, growing population and rising number of vehicles and transport development. In Delhi the prime source of noise pollution is vehicular traffic. In Delhi it is found that the ambient noise level (Leq) is exceeding the standard permissible value at all the locations. Noise barriers or enclosures are definitely useful in obtaining effective deduction of traffic noise disturbances in urbanized areas. US’s Federal Highway Administration Model (FHWA) and Calculation of Road Traffic Noise (CORTN) of UK are used to develop spread sheets for noise prediction. Spread sheets are also developed for evaluating effectiveness of existing boundary walls abutting houses in mitigating noise, redesigning them as noise barriers. Study was also carried out to examine the changes in noise level due to designed noise barrier by using both models FHWA and CORTN respectively. During the collection of various data it is found that receivers are located far away from road at Rithala and Moolchand sites and hence extra barrier height needed to meet prescribed limits was less as seen from calculations and most of the noise diminishes by propagation effect.On the basis of overall study and data analysis, it is concluded that FHWA and CORTN models under estimate noise levels. FHWA model predicted noise levels with an average percentage error of -7.33 and CORTN predicted with an average percentage error of -8.5. It was observed that at all sites noise levels at receivers were exceeding the standard limit of 55 dB. It was seen from calculations that existing walls are reducing noise levels. Average noise reduction due to walls at Rithala was 7.41 dB and at Panchsheel was 7.20 dB and lower amount of noise reduction was observed at Friend colony which was only 5.88. It was observed from analysis that Friends colony sites need much greater height of barrier. This was because of residential buildings abutting the road. At friends colony great amount of traffic was observed since it is national highway. At this site diminishing of noise due to propagation effect was very less.As FHWA and CORTN models were developed in excel programme, it eliminates laborious calculations of noise. There was no reflection correction in FHWA models as like in CORTN model.

Keywords: IFHWA, CORTN, Noise Sources, Noise Barriers

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Authors: Damien Gondre, Hatem Ben Maad, Abdelkrim Trabelsi, Frédéric Kuznik, Joseph Virgone

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The use of a radiant cooling solution would enable to lower cooling needs which is of great interest when the demand is initially high (hot climate). But, radiant systems are not naturally compatibles with humid climates since a low-temperature surface leads to condensation risks as soon as the surface temperature is close to or lower than the dew point temperature. A radiant cooling system combined to a dehumidification system would enable to remove humidity for the space, thereby lowering the dew point temperature. The humidity removal needs to be especially effective near the cooled surface. This requirement could be fulfilled by a system using a single desiccant fluid for the removal of both excessive heat and moisture. This task aims at providing an estimation of the specification requirements of such system in terms of cooling power and dehumidification rate required to fulfill comfort issues and to prevent any condensation risk on the cool panel surface. The present paper develops a preliminary study on the specification requirements, performances and behavior of a combined dehumidifier/cooling ceiling panel for different operating conditions. This study has been carried using the TRNSYS software which allows nodal calculations of thermal systems. It consists of the dynamic modeling of heat and vapor balances of a 5m x 3m x 2.7m office space. In a first design estimation, this room is equipped with an ideal heating, cooling, humidification and dehumidification system so that the room temperature is always maintained in between 21^◦C and 25^◦C with a relative humidity in between 40% and 60%. The room is also equipped with a ventilation system that includes a heat recovery heat exchanger and another heat exchanger connected to a heat sink. Main results show that the system should be designed to meet a cooling power of 42W.m⁻² and a desiccant rate of 45 g_H2O.h⁻¹. In a second time, a parametric study of comfort issues and system performances has been achieved on a more realistic system (that includes a chilled ceiling) under different operating conditions. It enables an estimation of an acceptable range of operating conditions. This preliminary study is intended to provide useful information for the system design.

Keywords: dehumidification, nodal calculation, radiant cooling panel, system sizing

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Authors: Ali Kamal M. Sami, Safa Almukhtar, Alaa Al-Krush, Ismael Hama-Amin Akha Weas, Ruqaya Ahmed Alqais

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Introduction and Objectives Lower urinary tract symptoms (LUTS) are common among men with benign prostatic hyperplasia (BPH). The combination of 5 alpha-reductase inhibitors and alpha-blockers has been used as a conservative treatment of male LUTS secondary to BPH. Nanotechnology structured water magnalife is a type of water that is produced by modulators and specific frequency and energy fields that transform ordinary water into this Nanowater. In this study, we evaluated the use of Nano-water with the conservative treatment and to see if it improves the outcome and gives better results in those patients with LUTS/BPH. Material and methods For a period of 3 months, 200 men with International Prostate Symptom Score (IPSS)≥13, maximum flow rate (Qmax)≤ 15ml/s, and prostate volume > 30 and <80 ccs were randomly divided into two groups. Group A 100 men were given Nano-water with the (tamsulosindutasteride) and group B 100 men were given ordinary bottled water with the (tamsulosindutasteride). The water bottles were unlabeled and were given in a daily dose of 20ml/kg body weight. Dutasteride 0.5mg and tamsulosin 0.4 mg daily doses. Both groups were evaluated for the IPSS, Qmax, Residual Urine (RU), International Index of Erectile Function–Erectile Function (IIEF-EF) domain at the beginning (baseline data), and at the end of the 3 months. Results Of the 200 men with LUTS who were included in this study, 193 men were followed, and 7 men dropped out of the study for different reasons. In group A which included 97 men with LUTS, IPSS decreased by 16.82 (from 20.47 to 6.65) (P<0.00001) and Qmax increased by 5.73 ml/s (from 11.71 to 17.44) (P<0.00001) and RU <50 ml in 88% of patients (P<0.00001) and IIEF-EF increased to 26.65 (from 16.85) (P<0.00001). While in group B, 96 men with LUTS, IPSS decreased by 8.74(from 19.59 to 10.85)(P<0.00001) and Qmax increased by 4.67 ml/s(from 10.74 to 15.41)(P<0.00001), RU<50 ml in 75% of patients (P<0.00001), and IIEF-EF increased to 21(from 15.87)(P<0.00001). Group A had better results than group B. IPSS in group A decreased to 6.65 vs 10.85 in group B(P<0.00001), also Qmax increased to 17.44 in group A vs 15.41 in group B(P<0.00001), group A had RU <50 ml in 88% of patients vs 75% of patients in group B(P<0.00001).Group A had better IIEF-EF which increased to 26.65 vs 21 in group B(P<0.00001). While the differences between the baseline data of both groups were statistically not significant. Conclusion The use of nanotechnology structured water magnalife gives a better result in terms of LUTS and scores in patients with BPH. This combination is showing improvements in IPSS and even in erectile function in those men after 3 months.

Keywords: nano water, lower urinary tract symptoms, benign prostatic hypertrophy, erectile dysfunction

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Authors: Vivek Kumar Gupta, Kripi Vohra, Monika Gupta

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Pulses have been a vital ingredient of the balanced human diet in India. Lentil (Lens culinaris Medikus or Lens esculenta Moench.) is a common legume known since biblical times. Lentil seeds, with or without hulls, are cooked as dhal and this has been the main dish for millennia in the South Asian region. Oxidative stress can damage lipids, proteins, enzymes, carbohydrates and DNA in cells and tissues, resulting in membrane damage, fragmentation or random cross linking of molecules like DNA, enzymes and structural proteins and even lead to cell death induced by DNA fragmentation and lipid peroxidation. These consequences of oxidative stress construct the molecular basis in the development of cancer, neurodegenerative disorders, cardiovascular diseases, diabetes and autoimmune. The aim of the present work is to assess the antioxidant potential of the peteroleum ether, acetone, methanol and water extract of the Lens esculenta seeds. In vitro antioxidant assessment of the extracts was carried out using 1,1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging activity, hydroxyl radical scavenging activity, reducing power assay. The quantitative estimation of total phenolic content, total flavonoid content in extracts and in plant material, total saponin content, total alkaloid content, crude fibre content, total volatile content, fat content and mucilage content in drug material was also carried out. Though all the extracts exhibited dose dependent reducing power activity the acetone extract was found to possess significant hydrogen donating ability in DPPH (45.83%-93.13%) and hydroxyl radical scavenging system (28.7%-46.41%) than the peteroleum ether, methanol and water extracts. Total phenolic content in the acetone and methanol extract was found to be 608 and 188 mg gallic acid equivalent of phenol/g of sample respectively. Total flavonoid content of acetone and methanol extract was found to be 128 and 30.6 mg quercetin equivalent/g of sample respectively. It is evident that acetone extract of Lentil seeds possess high levels of polyphenolics and flavonoids that could be utilized as antioxidants and neutraceuticals.

Keywords: antioxidant, flavanoids, Lens esculenta, polyphenols

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Authors: Boris Nemzer, Tania Reyes-Izquierdo, Zbigniew Pietrzkowski

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Glucosinolate is a family of glucosides that can be found in a family of brassica vegetables. Upon the damage of the plant, glucosinolate breakdown by an internal enzyme myrosinase (thioglucosidase; EC 3.2.3.1) into isothiocyanates, such as sulforaphane. Sulforaphane is formed by glucoraphanin cleaving the sugar off by myrosinase and rearranged. Sulforaphane nitrile is formed in the same reaction as sulforaphane with the active of epithiospecifier protein (ESP). Most common food processing procedure would break the plant and mix the glucoraphanin and myrosinase together, and the formed sulforaphane would be further degraded. The purpose of this study is to understand the glucoraphanin/sulforaphane and the myrosinase activity of broccoli seeds germinated at a different time and technological processing conditions that keep the activity of the enzyme to form sulforaphane. Broccoli seeds were germinated in the house. Myrosinase activities were tested as the glucose content using glucose assay kit and measured UV-Vis spectrophotometer. Glucosinolates were measured by HPLC/DAD. Sulforaphane was measured using HPLC-DAD and GC/MS. The 6 hr germinated sprouts have a myrosinase activity 32.2 mg glucose/g, which is comparable with 12 and 24 hour germinated seeds and higher than dry seeds. The glucoraphanin content in 6 hour germinated sprouts is 13935 µg/g which is comparable to 24 hour germinated seeds and lower than the dry seeds. GC/MS results show that the amount of sulforaphane is higher than the amount of sulforaphane nitrile in seeds, 6 hour and 24 hour germinated seeds. The ratio of sulforaphane and sulforaphane nitrile is high in 6 hour germinated seeds, which indicates the inactivated ESP in the reaction. After evaluating the results, the short time germinated seeds can be used as the source of glucoraphanin and myrosinase supply to form potential higher sulforaphane content. Broccoli contains glucosinolates, glucoraphanin (4-methylsulfinylbutyl glucosinolate), which is an important metabolite with health-promoting effects. In the pilot clinical study, we observed the effects of a glucosinolates/glucoraphanin-rich extract from short time germinated broccoli seeds on blood adenosine triphosphate (ATP), reactive oxygen species (ROS) and lactate levels. A single dose of 50 mg of broccoli sprouts extract increased blood levels of ATP up to 61% (p=0.0092) during the first 2 hours after the ingestion. Interestingly, this effect was not associated with an increase in blood ROS or lactate. When compared to the placebo group, levels of lactate were reduced by 10% (p=0.006). These results indicate that broccoli germinated seed extract may positively affect the generation of ATP in humans. Due to the preliminary nature of this work and promising results, larger clinical trials are justified.

Keywords: broccoli glucosinolates, glucoraphanin, germinated seeds, myrosinase, adenosine triphosphate

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Authors: Bashair Al Riyami

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Background: Acylation stimulating protein (ASP) is a small basic protein that was isolated based on its function as a potent lipogenic factor. The role of ASP in lipid metabolism has been described in numerous studies. Several association studies suggest that ASP may play a prominent role in female fat metabolism and distribution. Progesterone is established as a female lipogenic hormone, however the mechanisms by which progesterone exert its effects are not fully understood. AIM: Since ASP is an established potent lipogenic factor with a known mechanism of action, in this study we aim to investigate acute effects of different hormone treatments on ASP levels in vivo after a fat load. Methods: This is a longitudinal study including 24 female wister rats that were randomly divided into 4 groups including controls (n=6). The rats were ovariectomized, and fourteen days later the fasting rats were injected subcutaneously with a single dose of different hormone treatments (progesterone, estrogen and testosterone). An hour later, olive was administered by oral gavage, and plasma blood samples were collected at several time points after oil administration for ASP and triglyceride measurements. Area under the curve (TG-AUC) was calculated to represent TG clearance Results: RM-ANCOVA and post-analysis showed that only the progesterone treated group had a significant postprandial ASP increase at two hours compared to basal levels and to the controls (439.8± 62.4 vs 253.45± 59.03 ug/ml), P= 0.04. Interestingly, increased postprandial ASP levels coordinated negatively with corresponding TG levels and TG-AUC across the postprandial period most apparent in the progesterone and testosterone treated groups that behaved in an opposite manner. ASP levels were 3-fold higher in the progesterone compared to the testosterone treated group, whereas TG-AUC was significantly lower in the progesterone treated group compared to the testosterone treated group. Conclusion: These findings suggest that progesterone treatment enhances ASP production and TG clearance in a simultaneous manner. The strong association of postprandial ASP levels and TG clearance in the progesterone treated group support the notion of a stimulatory role for progesterone on ASP mediated TG clearance. This is the first functional study to demonstrate a cause-effect relationship between hormone treatment and ASP levels in vivo. These findings are promising and may contribute to further understanding the mechanism of progesterone function as a female lipogenic hormone through enhancing ASP production and plasma levels.

Keywords: ASP, lipids, sex hormones, wister rats

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Authors: Amela Ajanovic, Reinhard Haas

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Electric vehicles (EVs) are considered as an important means to cope with current environmental problems in transport. However, their high capital costs and limited driving ranges state major barriers to a broader market penetration. The core objective of this paper is to investigate the future market prospects of various types of EVs from an economic and ecological point of view. Our method of approach is based on the calculation of total cost of ownership of EVs in comparison to conventional cars and a life-cycle approach to assess the environmental benignity. The most crucial parameters in this context are km driven per year, depreciation time of the car and interest rate. The analysis of future prospects it is based on technological learning regarding investment costs of batteries. The major results are the major disadvantages of battery electric vehicles (BEVs) are the high capital costs, mainly due to the battery, and a low driving range in comparison to conventional vehicles. These problems could be reduced with plug-in hybrids (PHEV) and range extenders (REXs). However, these technologies have lower CO₂ emissions in the whole energy supply chain than conventional vehicles, but unlike BEV they are not zero-emission vehicles at the point of use. The number of km driven has a higher impact on total mobility costs than the learning rate. Hence, the use of EVs as taxis and in car-sharing leads to the best economic performance. The most popular EVs are currently full hybrid EVs. They have only slightly higher costs and similar operating ranges as conventional vehicles. But since they are dependent on fossil fuels, they can only be seen as energy efficiency measure. However, they can serve as a bridging technology, as long as BEVs and fuel cell vehicle do not gain high popularity, and together with PHEVs and REX contribute to faster technological learning and reduction in battery costs. Regarding the promotion of EVs, the best results could be reached with a combination of monetary and non-monetary incentives, as in Norway for example. The major conclusion is that to harvest the full environmental benefits of EVs a very important aspect is the introduction of CO₂-based fuel taxes. This should ensure that the electricity for EVs is generated from renewable energy sources; otherwise, total CO₂ emissions are likely higher than those of conventional cars.

Keywords: costs, mobility, policy, sustainability,

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Authors: Dipanshu Sur, Ratnabali Chakravorty, Rimi Pal, Siddhartha Chatterjee, Joyshree Chaterjee, Amal Mallik

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Background: Polycystic ovary syndrome (PCOS) is a common endocrine disease in reproductive women with a complex hormonal disturbance that affects the menstrual cycle and leads to metabolic consequences in later life. Hyperandrogenaemia is noticeable features of PCOS and influence the process of folliculogenesis in women. The levels of Antimüllerian Hormone (AMH) reflect the number of pre-antral follicles and thus are a marker of oocyte pool – germinal reserve of the ovary for reproduction. Besides its utilization in IVF (In-vitro fertilization), determination of AMH may serve as an additional marker in the diagnostics of PCOS, where increased AMH levels reflect the severity of the disease. The positive correlation of serum AMH with the number of antral follicles was found also in patients with PCOS. Objective: The objective of this study was to investigate the relationship between AMH androgens and whether AMH contributes to altered folliculogenesis in non-obese women with PCOS. Methods: We designed a prospective study which included a total of 65 IVF individuals. It enrolled 26 cases of PCOS based on 2003 Rotterdam criteria and 39 ovulatory normal- non PCOS, healthy, age-matched controls. AMH levels and ovarian morphology were assessed. The relationships between AMH and androgenaemia in patients with and without PCOS were studied. Results: Mean age of PCOS patients were slightly higher than controls (32±4 and 28±3 years, respectively). AMH generally increased with antral follicle count (AFC) [P=0.001], testosterone, and luteinising hormone, and decreased with age, and serum sex hormone binding globulin (SHBG). No significant relationships were found between circulating AMH levels and BMI between PCOS and non-PCOS patients. The calculation of AMH production per antral follicle (AMH/AF) showed that there was a significant difference in median AMH/AF between PCOS and non-PCOS (P =0.001). Both PCOS and non-PCOS groups showed a very similar increase in AMH with increases in AFC, but the PCOS patients had consistently higher AMH across all AFC levels. Conclusions: These observations indicate that there is a connection between AMH and androgens levels between PCOS and non-PCOS East Indian women. Excessive granulosa cell activity may be implicated in the abnormal follicular dynamic of the syndrome. They are higher in women with PCOS and, on the other hand, very low in women with an ovarian failure.

Keywords: anti-Mullerian hormone, polycystic ovary syndrome, antral follicle count, androgens

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Authors: Iva Blazkova, Amitava Moulick, Vedran Milosavljevic, Pavel Kopel, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

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Doxorubicin is one of the most commonly used and the most effective chemotherapeutic drugs. This antracycline drug isolated from the bacteria Streptomyces peuceticus var. caesius is sold under the trade name Adriamycin (hydroxydaunomycin, hydroxydaunorubicin). Doxorubicin is used in single therapy to treat hematological malignancies (blood cancers, leukaemia, lymphoma), many types of carcinoma (solid tumors) and soft tissue sarcomas. It has many serious side effects like nausea and vomiting, hair lost, myelosupression, oral mucositis, skin reactions and redness, but the most serious one is the cardiotoxicity. Because of the risk of heart attack and congestive heart failure, the total dose administered to patients has to be accurately monitored. With the aim to lower the side effects and to targeted delivery of doxorubicin into the tumor tissue, the different nanoparticles are studied. The drug can be bound on a surface of nanoparticle, encapsulated in the inner cavity, or incorporated into the structure of nanoparticle. Among others, carbon nanoparticles (graphene, carbon nanotubes, fullerenes) are highly studied. Besides the number of inorganic nanoparticles, a great potential exhibit also organic ones mainly lipid-based and polymeric nanoparticle. The aim of this work was to perform a toxicity study of free doxorubicin compared to doxorubicin conjugated with various nanotransporters. The effect of liposomes, fullerenes, graphene, and carbon nanotubes on the toxicity was analyzed. As a first step, the binding efficacy of between doxorubicin and the nanotransporter was determined. The highest efficacy was detected in case of liposomes (85% of applied drug was encapsulated) followed by graphene, carbon nanotubes and fullerenes. For the toxicological studies, the chicken embryos incubated under controlled conditions (37.5 °C, 45% rH, rotation every 2 hours) were used. In 7th developmental day of chicken embryos doxorubicin or doxorubicin-nanotransporter complex was applied on the chorioallantoic membrane of the eggs and the viability was analyzed every day till the 17th developmental day. Then the embryos were extracted from the shell and the distribution of doxorubicin in the body was analyzed by measurement of organs extracts using laser induce fluorescence detection. The chicken embryo mortality caused by free doxorubicin (30%) was significantly lowered by using the conjugation with nanomaterials. The highest accumulation of doxorubicin and doxorubicin nanotransporter complexes was observed in the liver tissue

Keywords: doxorubicin, chicken embryos, nanotransporters, toxicity

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Authors: Thayse Marques Passos, Brid Quilty, Mary Pryce

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The interest in developing alternative techniques to obtain safe water, free from pathogens and hazardous substances, is growing in recent times. The photodynamic inactivation of microorganisms (PDI) is a promising ecologically-friendly and multi-target approach for water disinfection. It uses visible light as an energy source combined with a photosensitiser (PS) to transfer energy/electrons to a substrate or molecular oxygen generating reactive oxygen species, which cause cidal effects towards cells. PDI has mainly been used in clinical studies and investigations on its application to disinfect water is relatively recent. The majority of studies use planktonic cells. However, in their natural environments, bacteria quite often do not occur as freely suspended cells (planktonic) but in cell aggregates that are either freely floating or attached to surfaces as biofilms. Microbes can form aggregates and biofilms as a strategy to protect them from environmental stress. As aggregates, bacteria have a better metabolic function, they communicate more efficiently, and they are more resistant to biocide compounds than their planktonic forms. Among the bacteria that are able to form aggregates are members of the genus Pseudomonas, they are a very diverse group widely distributed in the environment. Pseudomonas species can form aggregates/biofilms in water and can cause particular problems in water distribution systems. The aim of this study was to evaluate the effectiveness of photodynamic inactivation in killing a range of planktonic cells including Escherichia coli DSM 1103, Staphylococcus aureus DSM 799, Shigella sonnei DSM 5570, Salmonella enterica and Pseudomonas putida DSM 6125, and aggregating cells of Pseudomonas fluorescens DSM 50090, Pseudomonas aeruginosa PAO1. The experiments were performed in glass Petri dishes, containing the bacterial suspension and the photosensitiser, irradiated with a multi-LED (wavelengths 430nm and 660nm) for different time intervals. The responses of the cells were monitored using the pour plate technique and confocal microscopy. The study showed that bacteria belonging to Pseudomonads group tend to be more tolerant to PDI. While E. coli, S. aureus, S. sonnei and S. enterica required a dosage ranging from 39.47 J/cm2 to 59.21 J/cm2 for a 5 log reduction, Pseudomonads needed a dosage ranging from 78.94 to 118.42 J/cm2, a higher dose being required when the cells aggregated.

Keywords: bacterial aggregation, photoinactivation, Pseudomonads, water disinfection

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Authors: Chia-Yu Lin, Yu-Hsiang Shen, Cing-Ciao Ke, Chia-Hao Chang, Fan-Pin Tseng, Yu-Ching Ni, Sheng-Pin Tseng

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Tomosynthesis is an imaging system that generates a 3D image by scanning in a limited angular range. It could provide more depth information than traditional 2D X-ray single projection. Radiation dose in tomosynthesis is less than computed tomography (CT). Because of limited angular range scanning, there are many properties depending on scanning direction. Therefore, non-coplanar imaging technique was developed to improve image quality in traditional tomosynthesis. The purpose of this study was to establish the non-coplanar imaging technique of tomosynthesis system and evaluate this technique by the reconstructed image. INER prototype tomosynthesis system contains an X-ray tube, a flat panel detector, and a motion machine. This system could move X-ray tube in multiple directions during the acquisition. In this study, we investigated three different imaging techniques that were 2D X-ray single projection, traditional tomosynthesis, and non-coplanar tomosynthesis. An anthropopathic chest phantom was used to evaluate the image quality. It contained three different size lesions (3 mm, 5 mm and, 8 mm diameter). The traditional tomosynthesis acquired 61 projections over a 30 degrees angular range in one scanning direction. The non-coplanar tomosynthesis acquired 62 projections over 30 degrees angular range in two scanning directions. A 3D image was reconstructed by iterative image reconstruction algorithm (ML-EM). Our qualitative method was to evaluate artifacts in tomosynthesis reconstructed image. The quantitative method was used to calculate a peak-to-valley ratio (PVR) that means the intensity ratio of the lesion to the background. We used PVRs to evaluate the contrast of lesions. The qualitative results showed that in the reconstructed image of non-coplanar scanning, anatomic structures of chest and lesions could be identified clearly and no significant artifacts of scanning direction dependent could be discovered. In 2D X-ray single projection, anatomic structures overlapped and lesions could not be discovered. In traditional tomosynthesis image, anatomic structures and lesions could be identified clearly, but there were many artifacts of scanning direction dependent. The quantitative results of PVRs show that there were no significant differences between non-coplanar tomosynthesis and traditional tomosynthesis. The PVRs of the non-coplanar technique were slightly higher than traditional technique in 5 mm and 8 mm lesions. In non-coplanar tomosynthesis, artifacts of scanning direction dependent could be reduced and PVRs of lesions were not decreased. The reconstructed image was more isotropic uniformity in non-coplanar tomosynthesis than in traditional tomosynthesis. In the future, scan strategy and scan time will be the challenges of non-coplanar imaging technique.

Keywords: image reconstruction, non-coplanar imaging technique, tomosynthesis, X-ray imaging

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Authors: Michal Biały, Konrad Pietrykowski, Rafal Sochaczewski

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The kinematics and dynamics analysis of crank-piston system of aircraft engine. The object of the study was the high power aircraft engine ASz 62-IR. This engine is produced by a Polish company WSK "PZL-KALISZ" S.A.". All analyzes were performed numerically using CAD and CAE environment. Three-dimensional model of the crank-piston system was developed based on real engine located in the Laboratory of Centre of Innovation and Advanced Technologies of Lublin University of Technology. During the development of the model, the technique of reverse engineering - 3D scanning was used. ASz 62-IR engine is characterized by a radial type of crank-piston system. In this system the cylinders are arranged radially around the circle. This crank-piston system consists of a main connecting rod and eight additional connecting rods. In addition, three-dimensional model consists of a piston pins, pistons and piston rings. As a result of the specific engine design, characteristics of the piston individual movement are slightly different from each other. But the model assumes that they are the same during the analysis. Three-dimensional model of the engine was implemented into the MSC Adams software. The environment of MSC Adams allows for multibody simulation of the dynamic phenomena. This determines the state parameters of the moving elements, among which the load or force distribution on each kinematic node can be distinguished. Materials and characteristic materials parameters were adopted on the basis of commonly used materials for engine parts. The mass values of individual elements were adopted on the basis of real engine parts. The piston gas forces were replaced by calculation of pressure variations recorded during engine tests on the engine test bench. The research the changes of forces acting in the individual kinematic pairs of crank-piston system. The model allows to determine the load on the crankshaft main bearings. This gives the possibility for the main supports forces analysis The model allows for testing and simulation of kinematics and dynamics of a radial aircraft engine. This is the first stage of the work, which aims to numerical simulation of vibration of multi-cylinder aircraft engine. This work has been financed by the Polish National Centre for Research and Development, INNOLOT, under Grant Agreement No. INNOLOT/I/1/NCBR/2013.

Keywords: aircraft engine, CAD, CAE, dynamics, kinematics, MSC Adams, numerical simulation

Procedia PDF Downloads 366

Authors: Stig H. Jørgensen, Trond Nordfjærn, Øyvind Teige Hedenstrøm, Torbjørn Rundmo

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The aim of the paper is to estimate and forecast road traffic injuries in the coming 10-15 years given new targets in urban transport policy and shifts of mode of transport, including injury cross-effects of mode changes. The paper discusses possibilities and limitations in measuring and quantifying possible injury reductions. Injury data (killed and seriously injured road users) from six urban areas in Norway from 1998-2012 (N= 4709 casualties) form the basis for estimates of changing injury patterns. For the coming period calculation of number of injuries and injury rates by type of road user (categories of motorized versus non-motorized) by sex, age and type of road are made. A prognosticated population increase (25 %) in total population within 2025 in the six urban areas will curb the proceeded fall in injury figures. However, policy strategies and measures geared towards a stronger modal shift from use of private vehicles to safer public transport (bus, train) will modify this effect. On the other side will door to door transport (pedestrians on their way to/from public transport nodes) imply a higher exposure for pedestrians (bikers) converting from private vehicle use (including fall accidents not registered as traffic accidents). The overall effect is the sum of these modal shifts in the increasing urban population and in addition diminishing return to the majority of road safety countermeasures has also to be taken into account. The paper demonstrates how uncertainties in the various estimates (prediction factors) on increasing injuries as well as decreasing injury figures may partly offset each other. The paper discusses road safety policy and welfare consequences of transport mode shift, including reduced use of private vehicles, and further environmental impacts. In this regard, safety and environmental issues will as a rule concur. However pursuing environmental goals (e.g. improved air quality, reduced co2 emissions) encouraging more biking may generate more biking injuries. The study was given financial grants from the Norwegian Research Council’s Transport Safety Program.

Keywords: road injuries, forecasting, reduced private care use, urban, Norway

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Authors: Francisco J. García-de-Quirós, Gianmarco Radice

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When considering small robots working in a cooperative community for Moon surface exploration, navigation and inter-nodes communication aspects become a critical issue for the mission success. For this approach to succeed, it is necessary however to deploy the required infrastructure for the robotic community to achieve efficient self-localization as well as relative positioning and communications between nodes. In this paper, an exploration mission concept in which two cooperative robotic systems co-exist is presented. This paradigm hinges on a community of reference agents that provide support in terms of communication and navigation to a second agent community tasked with exploration goals. The work focuses on the role of the agent community in charge of the overall support and, more specifically, will focus on the positioning and navigation methods implemented in RF microwave bands, which are combined with the communication services. An analysis of the different methods for range and position calculation are presented, as well as the main limiting factors for precision and resolution, such as phase and frequency noise in RF reference carriers and drift mechanisms such as thermal drift and random walk. The effects of carrier frequency instability due to phase noise are categorized in different contributing bands, and the impact of these spectrum regions are considered both in terms of the absolute position and the relative speed. A mission scenario is finally proposed, and key metrics in terms of mass and power consumption for the required payload hardware are also assessed. For this purpose, an application case involving an RF communication network in UHF Band is described, in coexistence with a communications network used for the single agents to communicate within the both the exploring agents as well as the community and with the mission support agents. The proposed approach implements a substantial improvement in planetary navigation since it provides self-localization capabilities for robotic agents characterized by very low mass, volume and power budgets, thus enabling precise navigation capabilities to agents of reduced dimensions. Furthermore, a common and shared localization radiofrequency infrastructure enables new interaction mechanisms such as spatial arrangement of agents over the area of interest for distributed sensing.

Keywords: cooperative robotics, localization, robot navigation, surface exploration

Procedia PDF Downloads 274

Authors: Y. Landkocz, P. Gosset, A. Héliot, C. Corbière, C. Vendeville, V. Keravec, S. Billet, A. Verdin, C. Monteil, D. Préterre, J-P. Morin, F. Sichel, T. Douki, P. J. Martin

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Air Pollution produced by automobile traffic is one of the main sources of pollutants in urban atmosphere and is largely due to exhausts of the diesel engine powered vehicles. The International Agency for Research on Cancer, which is part of the World Health Organization, classified in 2012 diesel engine exhaust as carcinogenic to humans (Group 1), based on sufficient evidence that exposure is associated with an increased risk for lung cancer. Amongst the strategies aimed at limiting exhausts in order to take into consideration the health impact of automobile pollution, filtration of the emissions and use of biofuels are developed, but their toxicological impact is largely unknown. Diesel exhausts are indeed complex mixtures of toxic substances difficult to study from a toxicological point of view, due to both the necessary characterization of the pollutants, sampling difficulties, potential synergy between the compounds and the wide variety of biological effects. Here, we studied the potential indirect genotoxicity of emission of Diesel engines through on-line exposure of rats in inhalation chambers to a subchronic high but realistic dose. Following exposure to standard gasoil +/- rapeseed methyl ester either upstream or downstream of a particle filter or control treatment, rats have been sacrificed and their lungs collected. The following indirect genotoxic parameters have been measured: (i) telomerase activity and telomeres length associated with rTERT and rTERC gene expression by RT-qPCR on frozen lungs, (ii) γH2AX quantification, representing double-strand DNA breaks, by immunohistochemistry on formalin fixed-paraffin embedded (FFPE) lung samples. These preliminary results will be then associated with global cellular response analyzed by pan-genomic microarrays, monitoring of oxidative stress and the quantification of primary DNA lesions in order to identify biological markers associated with a potential pro-carcinogenic response of diesel or biodiesel, with or without filters, in a relevant system of in vivo exposition.

Keywords: diesel exhaust exposed rats, γH2AX, indirect genotoxicity, lung carcinogenicity, telomerase activity, telomeres length

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Authors: Arefeh Arabaninezhad, Ali Fakher

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Since the deterministic analysis methods fail to take system uncertainties into account, probabilistic and non-probabilistic methods are suggested. Geotechnical analyses are used to determine the stress and deformation caused by construction; accordingly, many input variables which depend on ground behavior are required for geotechnical analyses. The Random Set approach is an applicable reliability analysis method when comprehensive sources of information are not available. Using Random Set method, with relatively small number of simulations compared to fully probabilistic methods, smooth extremes on system responses are obtained. Therefore random set approach has been proposed for reliability analysis in geotechnical problems. In the present study, the application of random set method in reliability analysis of deep excavations is investigated through three deep excavation projects which were monitored during the excavating process. A finite element code is utilized for numerical modeling. Two expected ranges, from different sources of information, are established for each input variable, and a specific probability assignment is defined for each range. To determine the most influential input variables and subsequently reducing the number of required finite element calculations, sensitivity analysis is carried out. Input data for finite element model are obtained by combining the upper and lower bounds of the input variables. The relevant probability share of each finite element calculation is determined considering the probability assigned to input variables present in these combinations. Horizontal displacement of the top point of excavation is considered as the main response of the system. The result of reliability analysis for each intended deep excavation is presented by constructing the Belief and Plausibility distribution function (i.e. lower and upper bounds) of system response obtained from deterministic finite element calculations. To evaluate the quality of input variables as well as applied reliability analysis method, the range of displacements extracted from models has been compared to the in situ measurements and good agreement is observed. The comparison also showed that Random Set Finite Element Method applies to estimate the horizontal displacement of the top point of deep excavation. Finally, the probability of failure or unsatisfactory performance of the system is evaluated by comparing the threshold displacement with reliability analysis results.

Keywords: deep excavation, random set finite element method, reliability analysis, uncertainty

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Authors: Grace Fangmin Tan, Elaine Yiling Tay, Elizabeth Huiwen Tham, Andrea Wei Ching Yeo

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Background: While accidental poisonings in children may seem unavoidable, knowledge of circumstances surrounding such incidents and identification of risk factors is important in the development of secondary prevention strategies. Some risk factors include age of the child, lack of adequate supervision and improper storage of substances. The aim of this study is to assess risk factors and circumstances influencing outcomes in these children. Methodology: A retrospective medical record review of all accidental poisoning cases presenting to the Children’s Emergency at National University Hospital (NUH), Singapore between January 2014 and December 2015 was conducted. Information on demographics, poisoning circumstances and clinical outcomes were collected. Results: Ninety-nine of a total of 186 poisoning cases were accidental ingestions, with a mean age of 4.7 (range 0.4 to 18.3 years). The gender distribution is rather equal with 52(52.5%) females and 47(47.5%) males. Seventy-nine (79.8%) were self-administered by the child and in 20 cases (20.2%), the substance was administered erroneously by caregivers 12/20 (60.0%) of whom were given the wrong drug dose while 8/20 (40.0%) were given the wrong substance. Self-administration was associated with presentation to the ED within 12 hours (p=0.027, OR 6.65, 95% CI 1.24-35.72). Notably, 94.9% of the cases involved substances kept within reach of the child. Sixty-nine (82.1%) had the substance kept in the original container, 3(3.6%) in food containers, 8(9.5%) in other containers and 4(4.8%) without a container. Of the 50 cases with information on labelling, 40/50(80.0%) were accurately labelled, 2/50 (4.0%) wrongly labelled, and 8/50 (16.0%) were unlabelled. Implicated substances included personal care products (11.1%), household cleaning products (3.0%), and different classes of drugs such as paracetamol (22.2%), antihistamines (17.2%) and sympathomimetics (8.1%). Children < 3 years of age were 4.8 times more likely to be poisoned by household substances than children >3 years of age (p=0.009, 95% CI 1.48-15.77). Prehospital interventions were more likely to have been done in poisoning with household substances (p=0.005, OR 6.12 95% CI 1.73-21.68). Fifty-nine (59.6%) were asymptomatic, 34 (34.3%) had a Poisoning Severity Score (PSS) grade of 1 (minor) and 6 (6.1%) grade 2 (moderate). Older children were 9.3 times more likely to be symptomatic (p<0.001, 95% CI 3.15-27.25). Thirty (32%) required admission. Conclusion: A significant proportion of accidental poisoning cases were due to medication administration errors by caregivers, which should be preventable. Risk factors for accidental poisoning included lack of adequate caregiver supervision, improper labelling and young age of the child. There is an urgent need to improve caregiver counselling during medication dispensing as well as to educate caregivers on basic child safety measures in the home to prevent future accidental poisonings.

Keywords: accidental, caregiver, paediatrics, poisoning

Procedia PDF Downloads 197

Authors: Lalita Subedi, Jae Kyoung Chae, Yong Un Park, Cho Kyo Hee, Lee Jae Hyuk, Kang Min Cheol, Sun Yeou Kim

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Neuroinflammation may mediate the relationship between low levels of estrogens and neurodegenerative disease. Estrogens are neuroprotective and anti-inflammatory in neurodegenerative disease models. Due to the long term side effects of estrogens, researches have been focused on finding an effective phytoestrogens for biological activities. Daidzein present in soybeans and its active metabolite equol (7-hydroxy-3-(4'-hydroxyphenyl)-chroman) bears strong antioxidant and anticancer showed more potent anti-inflammatory and neuroprotective role in neuroinflammatory model confirmed its in vitro activity with molecular mechanism through NF-κB pathway. Three major CNS cells Microglia (BV-2), Astrocyte (C6), Neuron (N2a) were used to find the effect of equol in inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), MAPKs signaling proteins, apoptosis related proteins by western blot analysis. Nitric oxide (NO) and prostaglandin E2 (PGE2) was measured by the Gries method and ELISA, respectively. Cytokines like tumor necrosis factor-α (TNF-α) and IL-6 were also measured in the conditioned medium of LPS activated cells with or without equol. Equol inhibited the NO production, PGE-2 production and expression of COX-2 and iNOS in LPS-stimulated microglial cells at a dose dependent without any cellular toxicity. At the same time Equol also showed promising effect in modulation of MAPK’s and nuclear factor kappa B (NF-κB) expression with significant inhibition of the production of proinflammatory cytokine like interleukin -6 (IL-6), and tumor necrosis factor -α (TNF-α). Additionally, it inhibited the LPS activated microglia-induced neuronal cell death by downregulating the apoptotic phenomenon in neuronal cells. Furthermore, equol increases the production of neurotrophins like NGF and increase the neurite outgrowth as well. In conclusion the natural daidzein metabolite equol are more active than daidzein, which showed a promising effectiveness as an anti-neuroinflammatory and neuroprotective agent via downregulating the LPS stimulated microglial activation and neuronal apoptosis. This work was supported by Brain Korea 21 Plus project and High Value-added Food Technology Development Program 114006-4, Ministry of Agriculture, Food and Rural Affairs.

Keywords: apoptosis, equol, neuroinflammation, phytoestrogen

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Authors: V. Radulescu, S. Dumitru

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Introduction: Determination of the temperature field inside a fluid in motion has many practical issues, especially in the case of turbulent flow. The phenomenon is greater when the solid walls have a different temperature than the fluid. The turbulent heat and mass transfer have an essential role in case of the thermal pollution, as it was the recorded during the damage of the Thermoelectric Power-plant Oradea (closed even today). Basic Methods: Solving the theoretical turbulent thermal pollution represents a particularly difficult problem. By using the semi-empirical theories or by simplifying the made assumptions, based on the experimental measurements may be assured the elaboration of the mathematical model for further numerical simulations. The three zones of flow are analyzed separately: the vicinity of the solid wall, the turbulent transition zone, and the turbulent core. For each area are determined the distribution law of temperature. It is determined the dependence of between the Stanton and Prandtl numbers with correction factors, based on measurements experimental. Major Findings/Results: The limitation of the laminar thermal substrate was determined based on the theory of Landau and Levice, using the assumption that the longitudinal component of the velocity pulsation and the pulsation’s frequency varies proportionally with the distance to the wall. For the calculation of the average temperature, the formula is used a similar solution as for the velocity, by an analogous mediation. On these assumptions, the numerical modeling was performed with a gradient of temperature for the turbulent flow in pipes (intact or damaged, with cracks) having 4 different diameters, between 200-500 mm, as there were in the Thermoelectric Power-plant Oradea. Conclusions: It was made a superposition between the molecular viscosity and the turbulent one, followed by addition between the molecular and the turbulent transfer coefficients, necessary to elaborate the theoretical and the numerical modeling. The concept of laminar boundary layer has a different thickness when it is compared the flow with heat transfer and that one without a temperature gradient. The obtained results are within the margin of error of 5%, between the semi-empirical classical theories and the developed model, based on the experimental data. Finally, it is obtained a general correlation between the Stanton number and the Prandtl number, for a specific flow (with associated Reynolds number).

Keywords: experimental measurements, numerical correlations, thermal pollution through pipelines, turbulent thermal flow

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Authors: Mohd Shazad, K. K. Gupta

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Vector borne diseases are a serious global concern. Aedes aegypti, the primary vector for viruses that cause dengue fever, dengue haemorrhagic fever, chikungunya and yellow fever is widespread over large areas of the tropics and subtropics. In last decade, diseases transmitted by Aedes aegypti are of serious concern. In past decade, number of cases of dengue fever, dengue hemorrhagic fever, and chikungunya has increased multifold. Present research work focused on impact of ethanol extract of Ocimum sanctum on dengue vector Aedes aegypti. 0-24 hr. old fourth instar larvae of lab-bred population of Aedes aegypti were exposed to ethanol leaf extract of Ocimum with concentrations ranging from 50 ppm to 400 ppm. Survival and development and the treated larvae and reproductive behaviour of the adults emerged from the treated larvae was evaluated. Our results indicated larvicidal potential of the leaf ethanol extract. The influence of the extract was dose dependent. 77.2% mortality was observed in the larvae exposed to 400 ppm for 24 hr. Treatment at lower concentrations revealed delayed toxicity. The larvae survived after treatment showed severe developmental anomalies. Consequently, there was the significant increase in duration of fourth instar larva. The L4 treated with 400-ppm extract moulted after 4.6 days; this was in sharp contrast to control where the larval period of the fourth instar lasts three days. The treated fourth instar larvae in many cases transformed into larva-pupa intermediates with the combination of larva, pupa characters. The larva-pupa intermediates had reduced life span and failed to moult successfully. The adults emerged from the larvae treated with lower doses had reduced reproductive potential. The females exhibited longer preoviposition period, reduced oviposition rate, abnormal oviposition behaviour and decreased fertility. Our studies indicated the possibility of the presence of JH mimic or JH analogue in the leaf ethanol extract of Ocimum. The present research work explored the potentials of Ocimum sanctum, also known as the queen of herbs, in integrated vector management programme of Aedes aegypti, which is a serious threat to human health.

Keywords: Aedes aegypti, development, mortality, Ocimum sanctum reproduction

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Authors: Mike Wei, Nebu Koshy, Koen van Besien, Giorgio Inghirami, Steven M. Horwitz

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T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived, and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 – 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64-year-old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romidepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression. The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient’s cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents. After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed.

Keywords: tofacitinib, ruxolitinib, T-cell prolymphocytic leukemia, JAK3

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Authors: A. Mohammad Abdul Motalib Momin, B. Sheikh Mohammad Adil Uddin, C. Md Mamunur Rashid, D. Sheikh Arman Mahbub, E. Mohammad Sazzad Rahman, F. Abdullah Faruque

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The present study was designed to investigate the antioxidant and cytotoxicity potential of methanol and pet ether extracts of the Lagenaria siceraria (LM, LP), Cucumis sativus (CSM, CSP), Cucurbita maxima (CMM, CMP) plants. For the phytochemical screening, crude extract was tested for the presence of different chemical groups. In Lagenaria siceraria the following groups were identified: alkaloids, steroids, glycosides and saponins for methanol extract and alkaloids, steroids, glycosides, tannins and saponins are for pet ether extract. Glycosides, steroids, alkaloids, saponins and tannins are present in the methanol extract of Cucumis sativus; the pet ether extract has the alkaloids, steroids and saponins. Glycosides, steroids, alkaloids, saponins and tannins are present in both the methanolic and pet ether extract of Cucurbita maxima. In vitro antioxidant activity of the extracts were performed using DPPH radical scavenging, nitric oxide (NO) scavenging, total antioxidant capacity, total phenol content, total flavonoid content, and Cupric Reducing Antioxidant Capacity assays. The most prominent antioxidant activity was observed with the CSM in the DPPH free radical scavenging test with an IC50 value of 1667.23±11.00271 μg/ml as opposed to that of standard ascorbic acid (IC50 value of 15.707± 1.181 μg/ml.) In total antioxidant capacity method, CMP showed the highest activity (427.81±11.4 mg ascorbic acid/g). The total phenolic and flavonoids content were determined by Folin-Ciocalteu Reagent and aluminium chloride colorimetric method, respectively. The highest total phenols and total flavonoids content were found in CMM and LP with the value of 79.06±16.06 mg gallic acid/g & 119.0±1.41 mg quercetin/g, respectively. In nitric oxide (NO) scavenging the most prominent antioxidant activity was observed in CMM with an IC50 value of 8.119± 0.0036 μg/ml. The Cupric reducing capacity of the extracts was strong and dose dependent manner and CSM showed lowest reducing capacity. The cytotoxicity was determined by Brine shrimp lethality test and among these extracts most potent cytotoxicity was shown by CMM with LC50 value 16.98 µg/ml. The obtained results indicate that the investigated plants could be potential sources of natural antioxidants and can be used for various types of diseases.

Keywords: antioxidant, cytotoxicity, methanol, petroleum ether

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Authors: Dean A. McCorkle, Ed W. Hellman, Rebekka M. Dudensing, Dan D. Hanselka

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The motivation for this study centers on the labor- and cost-intensive nature of wine and table grape production in the U.S., and the potential opportunities for precision mechanization using robotics to augment those production tasks that are labor-intensive. The objectives of this study are to evaluate the economic viability of grape production in five U.S. states under current operating conditions, identify common production challenges and tasks that could be augmented with new technology, and quantify a maximum price for new technology that growers would be able to pay. Wine and table grape production is primed for precision mechanization technology as it faces a variety of production and labor issues. Methodology: Using a grower panel process, this project includes the development of a representative wine grape vineyard in five states and a representative table grape vineyard in California. The panels provided production, budget, and financial-related information that are typical for vineyards in their area. Labor costs for various production tasks are of particular interest. Using the data from the representative budget, 10-year projected financial statements have been developed for the representative vineyard and evaluated using a stochastic simulation model approach. Labor costs for selected vineyard production tasks were evaluated for the potential of new precision mechanization technology being developed. These tasks were selected based on a variety of factors, including input from the panel members, and the extent to which the development of new technology was deemed to be feasible. The net present value (NPV) of the labor cost over seven years for each production task was derived. This allowed for the calculation of a maximum price for new technology whereby the NPV of labor costs would equal the NPV of purchasing, owning, and operating new technology. Expected Results: The results from the stochastic model will show the projected financial health of each representative vineyard over the 2015-2024 timeframe. Investigators have developed a preliminary list of production tasks that have the potential for precision mechanization. For each task, the labor requirements, labor costs, and the maximum price for new technology will be presented and discussed. Together, these results will allow technology developers to focus and prioritize their research and development efforts for wine and table grape vineyards, and suggest opportunities to strengthen vineyard profitability and long-term viability using precision mechanization.

Keywords: net present value, robotic technology, stochastic simulation, wine and table grapes

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Authors: Deborah Eric, Abbas Ahmad Khan

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Lead halide perovskites quantum dots have attracted immense scientific and technological interest for successful photovoltaic applications because of their remarkable optoelectronic properties. In this paper, we have simulated CsMAPbI3-xBrx based quantum dots to implement their use in intermediate band solar cells (IBSC). These types of materials exhibit optical and electrical properties distinct from their bulk counterparts due to quantum confinement. The conceptual framework provides a route to analyze the electronic properties of quantum dots. This layer of quantum dots optimizes the position and bandwidth of IB that lies in the forbidden region of the conventional bandgap. A three-dimensional MAPbI3 quantum dot (QD) with geometries including spherical, cubic, and conical has been embedded in the CsPbBr3 matrix. Bound energy wavefunction gives rise to miniband, which results in the formation of IB. If there is more than one miniband, then there is a possibility of having more than one IB. The optimization of QD size results in more IBs in the forbidden region. One band time-independent Schrödinger equation using the effective mass approximation with step potential barrier is solved to compute the electronic states. Envelope function approximation with BenDaniel-Duke boundary condition is used in combination with the Schrödinger equation for the calculation of eigen energies and Eigen energies are solved for the quasi-bound states using an eigenvalue study. The transfer matrix method is used to study the quantum tunneling of MAPbI3 QD through neighbor barriers of CsPbI3. Electronic states are computed using Schrödinger equation with effective mass approximation by considering quantum dot and wetting layer assembly. Results have shown the varying the quantum dot size affects the energy pinning of QD. Changes in the ground, first, second state energies have been observed. The QD is non-zero at the center and decays exponentially to zero at boundaries. Quasi-bound states are characterized by envelope functions. It has been observed that conical quantum dots have maximum ground state energy at a small radius. Increasing the wetting layer thickness exhibits energy signatures similar to bulk material for each QD size.

Keywords: perovskite, intermediate bandgap, quantum dots, miniband formation

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Authors: Turban Kar, Maitree Bhattacharyya

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Curcumin, a dietary antioxidant has been identified as a wonder molecule to possess therapeutic properties protecting the cellular macromolecules from oxidative damage. In our experimental study, we have explored the effectiveness of curcumin in protecting the structural paradigm of Human Serum Albumin (HSA) when exposed to gamma irradiation. HSA, being an important transport protein of the circulatory system, is involved in binding of variety of metabolites, drugs, dyes and fatty acids due to the presence of hydrophobic pockets inside the structure. HSA is also actively involved in the transportation of drugs and metabolites to their targets, because of its long half-life and regulation of osmotic blood pressure. Gamma rays, in its increasing concentration, results in structural alteration of the protein and superoxide radical generation. Curcumin, on the other hand, mitigates the damage, which has been evidenced in the following experiments. Our study explores the possibility for protection by curcumin during the molecular and conformational changes of HSA when exposed to gamma irradiation. We used a combination of spectroscopic methods to probe the conformational ensemble of the irradiated HSA and finally evaluated the extent of restoration by curcumin. SDS - PAGE indicated the formation of cross linked aggregates as a consequence of increasing exposure of gamma radiation. CD and FTIR spectroscopy inferred significant decrease in alpha helix content of HSA from 57% to 15% with increasing radiation doses. Steady state and time resolved fluorescence studies complemented the spectroscopic measurements when lifetime decay was significantly reduced from 6.35 ns to 0.37 ns. Hydrophobic and bityrosine study showed the effectiveness of curcumin for protection against radiation induced free radical generation. Moreover, bityrosine and hydrophobic profiling of gamma irradiated HSA in presence and absence of curcumin provided light on the formation of ROS species generation and the protective (magical) role of curcumin. The molecular mechanism of curcumin protection to HSA from gamma irradiation is yet unknown, though a possible explanation has been proposed in this work using Thioflavin T assay. It was elucidated, that when HSA is irradiated at low dose of gamma radiation in presence of curcumin, it is capable of retaining the native characteristic properties to a greater extent indicating stabilization of molecular structure. Thus, curcumin may be utilized as a therapeutic strategy to protect cellular proteins.

Keywords: Bityrosine content, conformational change, curcumin, gamma radiation, human serum albumin

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Authors: Sharat Chandra, Zilong Wang, Ru-Rong Ji, Andrey Bortsov

Abstract:

Chronic pain (CP) therapeutic approaches have limited efficacy. As a result, doctors are prescribing opioids for chronic pain, leading to opioid overuse, abuse, and addiction epidemic. Therefore, the development of effective and safe CP drugs remains an unmet medical need. Voltage-gated sodium (Nav) channels act as cardiovascular and neurological disorder’s molecular targets. Nav channels selective inhibitors are hard to design because there are nine closely-related isoforms (Nav1.1-1.9) that share the protein sequence segments. We are targeting the Nav1.7 found in the peripheral nervous system and engaged in the perception of pain. The objective of this project was to screen a 1.5 million compound library for identification of inhibitors for Nav1.7 with analgesic effect. In this study, we designed a protocol for identification of isoform-selective inhibitors of Nav1.7, by utilizing the prior information on isoform-selective antagonists. First, a similarity search was performed; then the identified hits were docked into a binding site on the fourth voltage-sensor domain (VSD4) of Nav1.7. We used the FTrees tool for similarity searching and library generation; the generated library was docked in the VSD4 domain binding site using FlexX and compounds were shortlisted using a FlexX score and SeeSAR hyde scoring. Finally, the top 25 compounds were tested with molecular dynamics simulation (MDS). We reduced our list to 9 compounds based on the MDS root mean square deviation plot and obtained them from a vendor for in vitro and in vivo validation. Whole-cell patch-clamp recordings in HEK-293 cells and dorsal root ganglion neurons were conducted. We used patch pipettes to record transient Na⁺ currents. One of the compounds reduced the peak sodium currents in Nav1.7-HEK-293 stable cell line in a dose-dependent manner, with IC50 values at 0.74 µM. In summary, our computer-aided analgesic discovery approach allowed us to develop pre-clinical analgesic candidate with significant reduction of time and cost.

Keywords: chronic pain, voltage-gated sodium channel, isoform-selective antagonist, similarity search, virtual screening, analgesics development

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