Search results for: dose volume histogram

Authors: Hany M. Fayed, Rehab F. Abdel-Rahman, Alyaa F. Hessin, Hanan A. Ogaly, Gihan F. Asaad, Abeer A. A. Salama, Sahar Abdelrahman, Mahmoud S. Arbid, Marwan Abd Elbaset Mohamed

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Liver fibrosis is a serious global health problem that occurs as a result of a variety of chronic liver disorders. Apigenin, a flavonoid found in many plants, has several pharmacological properties. The aim of this study was to evaluate the antifibrotic efficacy of apigenin (APG) against experimentally induced hepatic fibrosis in rats via using thioacetamide (TAA) and to explore the possible underlying mechanisms. TAA (100 mg/kg, i.p.) was given three times each week for two weeks to induce liver fibrosis. After TAA injections, APG was given orally (5 and 10 mg/kg) daily for two weeks. Biochemical, molecular, histological and immunohistochemical analyses were performed on blood and liver tissue samples. The functioning of the liver, oxidative stress, inflammation, and liver fibrosis indicators were all evaluated. The findings showed that TAA markedly increased the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), as well as the levels of malondialdehyde (MDA), focal adhesion kinase (FAK), hypoxia-inducible factor-1 (HIF-1), nuclear factor-κB (NF-κB), transforming growth factor-beta (TGF-β), tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β) with a reduction in albumin, total protein, A/G ratio, GSH content and interleukin-10 (IL-10). Moreover, TAA elevated the content of collagen I, α -smooth muscle actin (α-SMA), and hydroxyproline in the liver. The treatment with APG in a dose-dependent manner has obviously prevented these alterations and amended the harmful effects induced by TAA. The histopathological and immunohistochemical observations supported this biochemical evidence. The higher dose of APG produced the most significant antifibrotic effect. As a result of these data, APG appears to be a promising antifibrotic drug and could be used as a new herbal medication or dietary supplement in the future for the treatment of liver fibrosis. This effect might be related to the inhibition of the HIF-1/FAK signaling pathway.

Keywords: apigenin, FAK, HIF-1, liver fibrosis, rat, thioacetamide

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Authors: Benjaporn Buranrat, Nootchanat Mairuae

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Cratoxylum formosum (Jack) Dyer (CF) has been used for the traditional medicines in South East Asian and Thailand. Normally, northeast Thai vegetables have proven cytotoxic to many cancer cells. Therefore, the present study aims to explore the molecular mechanisms underlying CF-induced cancer cell death and apoptosis on breast and liver cancer cells. The cytotoxicity and antiproliferative effects of CF on the human breast MCF-7 and liver HepG2 cancer cell lines were evaluated using sulforhodamine B assay and colony formation assay. Cell migration assay was measured using wound healing assay. The apoptosis induction mechanisms were investigated through reactive oxygen species formation, caspase 3 activity, and JC-1 activity. Gene expression by real-time PCR and apoptosis related protein levels by Western blot analysis. CF induced MCF-7 and HepG2 cell death by time- and dose-dependent manner. Furthermore, CF had the greater cytotoxic potency on MCF-7 more than HepG2 cells with IC50 values of 85.70+4.52 μM and 219.03±9.96 μM respectively, at 24 h. Treatment with CF also caused a dose-dependent decrease in colony forming ability and cell migration, especially on MCF-7 cells. CF induced ROS formation, increased caspase 3 activities, and decreased the mitochondrial membrane potential, and causing apoptotic body production and DNA fragmentation. CF significantly decreased expression of the cell cycle regulatory protein RAC1 and downstream proteins, cdk6. Additionally, CF enhanced p21 and reduced cyclin D1 protein levels. CF leaf extract induced cell death, apoptosis, antimigration in both of MCF-7 and HepG2 cells. CF could be useful for developing to anticancer drug candidate for breast and liver cancer therapy.

Keywords: cratoxylum formosum (jack) dyer, breast cancer, liver cancer, cell death

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Authors: Ali Fazeli Moslehabadi

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One of the topics discussed in civil projects, during the execution of the project, which the continuous change of work volumes is usually the characteristics of these types of projects, is how to calculate the volume of done work. The difference in volumes announced by the execution unit with the estimated volume by the technical office unit, has direct effect on the announced progress of the project. This issue can show the progress of the project more or less than actual value and as a result making mistakes for stakeholders and project managers and misleading them. This article intends to introduce some practical methods for calculating the volume of done work in civil projects. It then reviews the strengths and weaknesses of each of them, in order to resolve these contradictions and conflicts.

Keywords: technical skills, systemic skills, communication skills, done work volume calculation techniques

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Authors: Jeng-Shin Sheu, Qi-Xun Zheng

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This paper mainly discusses a method of separating speech when using a microphone array without knowing the number and direction of sound sources. In recent years, there have been many studies on the method of separating signals by using masking, but most of the separation methods must be operated under the condition of a known number of sound sources. Such methods cannot be used for real-time applications. In our method, this paper uses Circular-Integrated-Cross-Spectrum to estimate the statistical histogram distribution of the direction of arrival (DOA) to obtain the number of sound sources and sound in the mixed-signal Source direction. In calculating the relevant parameters of the ring integrated cross-spectrum, the phase (Phase of the Cross-Power Spectrum) and phase rotation factors (Phase Rotation Factors) calculated by the cross power spectrum of each microphone pair are used. In the part of separating speech, it uses the DOA weighting and shielding separation method to calculate the sound source direction (DOA) according to each T-F unit (time-frequency point). The weight corresponding to each T-F unit can be used to strengthen the intensity of each sound source from the T-F unit and reduce the influence of the remaining sound sources, thereby achieving voice separation.

Keywords: real-time, spectrum analysis, sound source localization, sound source separation

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Authors: H. El-Messiry, M. El-Zainy, D. Ghazy

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Diabetes is a metabolic disease that results in a variety of oral health complications. Green tea is a natural antioxidant proved to have powerful effects against diabetes. The aim of this study was to compare between the effect of insulin and green tea on the Parotid gland of streptozotocin induced diabetic Albino rats by using light and transmission electron microscopy. Forty male Albino rats were divided into control group and diabetic groups. The diabetic group received a single injection of 40 mg/kg of streptozotocin intra-peritoneal under anesthesia and was further subdivided into three subgroups: The diabetic untreated subgroup which was untreated for two weeks, the insulin treated subgroup which has received insulin subcutaneously in a daily dose of 5 IU/kg body weight/day for two weeks and a green tea treated subgroup received a daily dose of 1 ml/ 100 gm body weight intragastrically for two weeks. Rats were terminated and parotid glands were dissected and processed for light and transmission electron microscopic examination. Histological examination of the diabetic untreated subgroup revealed acinar cells with pyknotic and hyperchromatic nuclei with cytoplasmic vacuolations. Ultrastructurally, acinar cells showed nuclear pleomorphism, dilated rough endoplasmic reticulum and swollen mitochondria with damaged cristae. Inflammatory cell infiltration was detected both histologically and ultrastructurally. Ducts showed signs of degeneration with loss of their normal outline and stagnated secretion within the lumen. However, insulin and green tea treated subgroups showed minimal degenerative damage and were almost similar to the control with minimal changes. Treatment of the parotid gland of the streptozotocin induced diabetic rats with GT was closely comparable to the traditional insulin therapy in reducing signs of histological and ultrastructural damage.

Keywords: diabetes, green tea, insulin, parotid

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Authors: Abir Mohamed Mohamed Ibrahim, Amina Titouche, Mohamed Hazzit

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Phytotherapy is based on use of plant natural products holding the main sources of drugs with healing properties for the treatment of human, animal or vegetable diseases. With these aims, and to replace chemical preservatives in natural products, we are interested to use essential oils from Algerian endemic plants belonging to the Asteraceae family: Artemisia herba alba Asso, which was undergoes a hydro-distillation after its irradiation by Gamma rays at frequencies: 10, 20, and 30 KGray which gave respectively the following essential oil yields: 1.087%, 1.087%, 1.085%, compared with that of the untreated sample giving a yield of 1.27 %. Evaluation of the antioxidant activity in vitro of essential oil for A. herba alba has been assessed by two different methods: inhibition of DPPH radical and measurement of reducing power. The first method has not revealed a very big difference regardless of the dose of irradiation, the IC50 is about 4000 mg/l, the maximum of inhibition was around 49.4%, likewise, the test of reducing power awarded us a maximum reducing capacity was of 0.76%; both of results were registered by the specimen irradiated at 20 KGy, it has a more better antioxidant power than no irradiated sample but slightly. To combat Fusarium culmorum, causing the wilts and rots, we are focused on the antifungal screening of this aromatic plant. The results obtained, followed by measurements of Minimal Inhibitory Concentrations (MIC); showed promising inhibitory effect against pathogen tested. With a yield superior to l%, the essential oil has shown a remarkable efficiency on the stump, mainly for sample irradiate at 30KGray (MICs= 625 µg/ml; MICc= 1250 µg/ml) with MIC of 2%. These results demonstrate a good antifungal activity, to limit and even to stop the development of the pathogenic microorganism and also the positive effect of dose of irradiation to upgrade this capacity as well, to uphold the antioxidant capacity.

Keywords: artemisia herba alba Asso, essential oil yield, gamma ray, antioxidant activity, antifungal activity

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Authors: Rajesh S. Mony, Vaidyaratnam Oushadhasala

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An attempt is made in this study to evolve a drug development modality based on classical Ayurvedic knowledge base as well as on modern scientific methodology. The present study involves (a) identification of a specific ailment condition, (b) the selection of a polyherbal formulation, (c) deciding suitable extraction procedure, (d) confirming the efficacy of the combination by in-vitro trials and (e) fixing up the recommended dose. The ailment segment selected is arthritic condition. The selected herbal combination is Kunturushka, Vibhitaki, Guggulu, Haridra, Maricha and Nirgundi. They were selected as per Classical Ayurvedic references, Authentified as per API (Ayurvedic Pharmacopeia of India), Extraction of each drug was done by different ratios of Hydroalcoholic menstrums, Invitro assessment of each extract after removing residual solvent for anti-Inflammatory, anti-arthritic activities (by UV-Vis. Spectrophotometer with positive control), Invitro assessment of each extract for COX enzyme inhibition (by UV-Vis. Spectrophotometer with positive control), Selection of the extracts was made having good in-vitro activity, Performed the QC testing of each selected extract including HPTLC, that is the in process QC specifications, h. Decision of the single dose with mixtures of selected extracts was made as per the level of in-vitro activity and available toxicology data, Quantification of major groups like Phenolics, Flavonoids, Alkaloids and Bitters was done with both standard Spectrophotometric and Gravimetric methods, Method for Marker assay was developed and validated by HPTLC and a good resolved HPTLC finger print was developed for the single dosage API (Active Pharmaceutical Ingredient mixture of extracts), Three batches was prepared to fix the in process and API (Active Pharmaceutical Ingredient) QC specifications.

Keywords: drug development, antiinflammatory, quality stardardisation, planar chromatography

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Authors: E. A. Abdel-Hakim

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The corn stemborer Sesamia cretica (Lederer), has been viewed in many parts of the world as a major pest of cultivated maize, graminaceous crops and sugarcane. Its life cycle is comprised of two different phases, one is the growth and developmental phase (non-diapause) and the other is diapause phase which takes place at the last larval instar. Several problems associated with the use of conventional insecticides, have strongly demonstrated the need for applying alternative safe compounds. Prominent among the prototypes of such prospective chemicals are the juvenoids; i.e. the insect (JH) mimics. In fact, the hormonal effect on metabolism has long been viewed as a secondary consequence of its direct action on specific energy-requiring biosynthetic mechanisms. Therefore, the present study was undertaken essentially in a rather systematic fashion as a contribution towards clarifying metabolic and energetic changes taking place during non-diapause wandering larvae as regulated by (JH) mimic. For this purpose, we applied two different doses of JH mimic (Ro 11-0111) in a single (standard) dose of 100µg or in a single dose of 20 µg/g bw in1µl acetone topically at the onset of nondiapause wandering larvae (WL). Energetic data were obtained by indirect calorimetry methods by conversion of respiratory gas exchange volumetric data, as measured manometrically using a Warburg constant respirometer, to caloric units (g-cal/g fw/h). The findings obtained can be given in brief; these treated larvae underwent supernumerary larval moults. However, this potential the wandering larvae proved to possess whereby restoration of larval programming for S. cretica to overcome stresses even at this critical developmental period. The results obtained, particularly with the high dose used, show that 98% wandering larvae were rescued to survive up to one month (vs. 5 days for normal controls), finally the formation of larval-adult intermediates. Also, the solvent controls had resulted in about 22% additional, but stationary moultings. The basal respiratory metabolism (O2 uptake and CO2 output) of the (WL), whether un-treated or larvae not had followed reciprocal U-shaped curves all along of their developmental duration. The lowest points stood nearly to the day of prepupal formation (571±187 µl O2/gfw/h and 553±181 µl CO2/gfw/h) during un-treated in contrast to the larvae treated with JH (210±48 µl O2/gfw/h and 335±81 µl CO2/gfw/h). Un-treated (normal) larvae proved to utilize carbohydrates as the principal source for energy supply; being fully oxidised without sparing any appreciable amount for endergonic conversion to fats. While, the juvenoid-treated larvae and compared with the acetone-treated control equivalents, there existed no distinguishable differences between them; both had been observed utilising carbohydrates as the sole source of energy demand and converting endergonically almost similar percentages to fats. The overall profile, treated and un-treated (WL) utilized carbohydrates as the principal source for energy demand during this stage.

Keywords: juvenile hormone, respiratory metabolism, Sesamia cretica, wandering phase

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Authors: Muhammad Zubair, Maqbool Ahmad, Al-Hafizah Shafia Tehseen Gul, Shujait Ali

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The use of vitamins has significant effects on the reproductive system of mammals. The present study was conducted to investigate the useful effects of vitamin E on reproductive functions of Teddy bucks. For this purpose, 8 adult Teddy bucks were randomly divided into two treatment groups viz; A (control) and B (vitamin E with dose of 200 mg/kg BW/day). These treatments continued for 12 weeks. Semen quality parameters (volume, motility, sperm morphology and sperm DNA integrity) of experimental bucks of each group was evaluated on weekly basis, while testicular measurements (length, scrotal circumference and weights) were recorded at 0 and 12th week of experiment. Serum concentrations of male sex hormones (testosterone, LH, FSH) and cortisol were recorded fortnightly. Similarly, body weights of bucks were also measured fortnightly until completion of the study. The data were subjected to two-way analysis of variance, followed by Duncan test for multiple mean comparisons. Supplementation of vitamin E improved significantly (P<0.05) the semen quality parameter, body weights, testicular measurements and serum levels of sex hormones. However, there was no effect on serum cortisol. It was concluded from the present study that dietary supplementation of vitamin E has beneficial effects on the semen and hormones in male reproductive system.

Keywords: hormones, semen, teddy bucks, testicular measurements

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Authors: Ritu Karwasra, Surender Singh

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Inflammation is an important physiological response of the body’s self-defense system that helps in eliminating and protecting organism from harmful stimuli and in tissue repair. It is a highly regulated protective response which helps in eliminating the initial cause of cell injury, and initiates the process of repair. The present study was designed to evaluate the ameliorative effect of pomegranate rind extract on pain and inflammation. Hydroalcoholic standardized rind extract of pomegranate at doses 50, 100 and 200 mg/kg and indomethacin (3 mg/kg) was tested against eddy’s hot plate induced thermal algesia, carrageenan (acute inflammation) and Complete Freund’s Adjuvant (chronic inflammation) induced models in Wistar rats. Parameters analyzed were inhibition of paw edema, measurement of joint diameter, levels of GSH, TBARS, SOD, TNF-α, radiographic imaging, tissue histology and synovial expression of pro-inflammatory cytokine receptor (TNF-R1). Radiological and light microscopical analysis were carried out to find out the bone damage in CFA-induced chronic inflammatory model. Findings of the present study revealed that pomegranate rind extract at a dose of 200 mg/kg caused a significant (p<0.05) reduction in paw swelling in both the inflammatory models. Nociceptive threshold was also significantly (p<0.05) improved. Immunohistochemical analysis of TNF-R1 in CFA-induced group showed elevated level, whereas reduction in level of TNF-R1 was observed in pomegranate (200 mg/kg). Henceforth, we might say that pomegranate produced a dose-dependent reduction in inflammation and pain along with the reduction in levels of oxidative stress markers and tissue histology, and the effect was found to be comparable to that of indomethacin. Thus, it can be concluded that pomegranate is a potential therapeutic target in the pathogenesis of inflammation and pain, and punicalagin is the major constituents found in rind extract might be responsible for the activity.

Keywords: carrageenan, inflammation, nociceptive-threshold, pomegranate, histopathology

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Authors: Benedict Ofori, Kwabena Sarpong, Stephen Antwi

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Background: Medicinal plants are utilized all around the world and are becoming increasingly important economically. The WHO notes that ‘inappropriate use of traditional medicines or practices can have negative or dangerous effects and that future research is needed to ascertain the efficacy and safety of such practices and medicinal plants used by traditional medicine systems. The poor around the world have limited access to palliative care or pain relief. Pharmacologists have been focused on developing safe and effective anti-inflammatory drugs. Most of the issues related to their use have been linked to the fact that numerous traditional and herbal treatments are classified in different nations as meals or dietary supplements. As a result, there is no need for evidence of the quality, efficacy, or safety of these herbal formulations before they are marketed. The fact that access to drugs meant for pain relief is limited in low-income countries means advanced studies should be done on home drugs meant for inflammation to close the gap. Methods: The ethanolic extracts of the plant were screened for the presence of 10 phytochemicals. The Pierce BCA Protein Assay Kit was used for the determination of the protein concentration of the egg white. The rats were randomly selected and put in 6 groups. The egg white was sub-plantar injected into the right-hand paws of the rats to induce inflammation. The animals were treated with the three plant extracts obtained from the root bark, stem, and leaves of the plant. The control groups were treated with normal saline, while the standard groups were treated with standard drugs indomethacin and celecoxib. Plethysmometer was used to measure the change in paw volume of the animals over the course of the experiment. Results: The results of the phytochemical screening revealed the presence of reducing sugars and saponins. Alkaloids were present in only R.L.S (1:1:1), and phytosterols were found in R.L(1:1) and R.L.S (1:1:1). The estimated protein concentration was found to be 103.75 mg/ml. The control group had an observable increase in paw volume, which indicated that inflammation was induced during the 5 hours. The increase in paw volume for the control group peaked at the 1st hour and decreased gradually throughout the experiment, with minimal changes in the paw volumes. The 2nd and 3rd groups were treated with 20 mg/kg of indomethacin and celecoxib. The anti-inflammatory activities of indomethacin and celecoxib were calculated to be 21.4% and 4.28%, respectively. The remaining 3 groups were treated with 2 dose levels of 200mg/kg plant extracts. R.L.S, R.L, and S.R.L had anti-inflammatory activities of 22.3%, 8.2%, and 12.07%, respectively. Conclusions: Egg albumin-induced paw model in rats can be used to evaluate the anti-inflammatory activity of herbs that might have potential anti-inflammatory activity. Herbal medications have potential anti-inflammatory activities and can be used to manage various inflammatory conditions if their efficacy and side effects are well studied. The three extracts all possessed anti-inflammatory activity, with R.L.S having the highest anti-inflammatory activity.

Keywords: inflammation, capparis erythrocarpos, anti-inflammatory activity, herbal medicine, paw volume, egg albumin

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Authors: Firas S. Azzeh

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Background: Vitamin C is a water soluble vitamin that is necessary for normal growth and development. Hyperuricemia is commonly detected in subjects with abnormal purine metabolism. Prolonged hyperuricemia is an important risk factor for damaged joint and often associated with gout. Objectives: To compare the effect of high dose of vitamin C supplements on uric acid treatment between hyperuricemic and gouty patients in Jeddah, Saudi Arabia, as well as finding out the effect of vitamin C on serum creatinine level and glomerular filtration rate (GFR). Subjects and Methods: This comparative study started on April 2013 and lasted tells March 2014. A convenience sample of 30 adults was recruited in this study from Doctor Abdulrahman Taha Bakhsh Hospital in Jeddah (Saudi Arabia). Eligible persons were assigned into two study groups; hyperuricemic (n=15) and gouty (n=15) groups. Subjects have been accepted for participating in the study after completing the consent form. Each participant consumed 500 mg/day vitamin C chew able tablets. All participants have been followed-up for 2 months. Twelve hours fasting blood samples have been collected 3 times from each participant during the study period; at the beginning before and retested after each month of the study period. Uric acid, serum creatinine and GFR were measured. Results: For gouty group, uric acid increased insignificantly after 2 months by about +0.3 mg/dl. On the other hand, hyperuricemic group showed decrease (P ≤ 0.05) in uric acid after 2 months of study period by about -0.78 mg/dl. Serum creatinine level insignificantly decreased for all participants during the study period, which leaded to insignificant increase in GFR for all participants. Conclusion: Supplementation with 500 mg/day vitamin C for 2 months significantly reduced serum uric acid for hyperuricemic patients and insignificantly increased serum uric acid for gouty patients. The ineffectiveness of vitamin C supplements on patients with established gout could be related to a number of potential reasons.

Keywords: vitamin c, Hyperuricemia, gout, creatinine, GFR

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Authors: Diana Larisa Vladoiu, Vasile Ostafe, Adriana Isvoran

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Molecular docking calculations reveal that pesticides provide favorable interactions with the bacterial chitinases. Pesticides interact with both hydrophilic and aromatic residues involved in the active site of the enzymes, their positions partially overlapping the substrate and the inhibitors locations. Molecular docking outcomes, in correlation with experimental literature data, suggest that the pesticides may be degraded or having an inhibitor effect on the activity of these enzymes, depending of the application dose and rate.

Keywords: chitinases, inhibition, molecular docking, pesticides

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Authors: Khalid Iqbal, Saima Altaf, M. Akram, Muhammad Abdur Rafaye, Saeed Ahmad Buzdar

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Objective: Verification of patient-specific intensity modulated radiation therapy (IMRT) plans using different 2-D detectors has become increasingly popular due to their ease of use and immediate readout of the results. The purpose of this study was to test and compare various 2-D detectors for dosimetric quality assurance (QA) of intensity-modulated radiotherapy (IMRT) with the vision to find alternative QA methods. Material and Methods: Twenty IMRT patients (12 of brain and 8 of the prostate) were planned on Eclipse treatment planning system using Varian Clinac DHX on both energies 6MV and 15MV. Verification plans of all such patients were also made and delivered to Map check2, EPID (Electronic portal imaging device) and Gafchromic EBT3. Gamma index analyses were performed using different criteria to evaluate and compare the dosimetric results. Results: Statistical analysis shows the passing rate of 99.55%, 97.23% and 92.9% for 6MV and 99.53%, 98.3% and 94.85% for 15 MV energy using a criteria of ±5% of 3mm, ±3% of 3mm and ±3% of 2mm respectively for brain, whereas using ±5% of 3mm and ±3% of 3mm gamma evaluation criteria, the passing rate is 94.55% and 90.45% for 6MV and 95.25%9 and 95% for 15 MV energy for the case of prostate using EBT3 film. Map check 2 results shows the passing rates of 98.17%, 97.68% and 86.78% for 6MV energy and 94.87%,97.46% and 88.31% for 15 MV energy respectively for brain using a criteria of ±5% of 3mm, ±3% of 3mm and ±3% of 2mm, whereas using ±5% of 3mm and ±3% of 3mm gamma evaluation criteria gives the passing rate of 97.7% and 96.4% for 6MV and 98.75%9 and 98.05% for 15 MV energy for the case of prostate. EPID 6 MV and gamma analysis shows the passing rate of 99.56%, 98.63% and 98.4% for the brain, 100% and 99.9% for prostate using the same criteria as for map check 2 and EBT 3 film. Conclusion: The results demonstrate excellent passing rates were obtained for all dosimeter when compared with the planar dose distributions for 6 MV IMRT fields as well as for 15 MV. EPID results are better than EBT3 films and map check 2 because it is likely that part of this difference is real, and part is due to manhandling and different treatment set up verification which contributes dose distribution difference. Overall all three dosimeter exhibits results within limits according to AAPM report.120.

Keywords: gafchromic EBT3, radiochromic film dosimetry, IMRT verification, EPID

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Authors: S. A. El-Marasy, S. A. El Awdan, R. M. Abd-Elsalam

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This study aimed to investigate the possible neuroprotective effect of chrysin on thioacetamide (TAA)-induced hepatic encephalopathy in rats. Also, the effect of chrysin on motor impairment, cognitive deficits, oxidative stress, neuroinflammation, apoptosis and histopathological damage was assessed. Male Wistar rats were randomly allocated into five groups. The first group received the vehicle (distilled water) for 21 days and is considered as normal group. While the second one received intraperitoneal dose of TAA (200 mg/kg) at three alternative days during the third week of the experiment to induce HE and is considered as control group. The other three groups were orally administered chrysin for 21 days (25, 50, 100 mg/kg) and starting from day 17; rats received intraperitoneal dose of TAA (200 mg/kg) at three alternative days. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Then behavioral, biochemical, histopathological and immunohistochemical analyses were assessed. Chrysin reversed TAA-induced motor coordination in rotarod test, cognitive deficits in object recognition test (ORT) and attenuated serum ammonia, hepatic liver enzymes, reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), reduced nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) brain contents. Chrysin administration also reduced Toll-4 receptor (TLR-4) gene expression, caspase-3 protein expression, hepatic necrosis and astrocyte swelling. This study depicts that chrysin exerted neuroprotective effect in TAA-induced HE rats, evidenced by improvement of cognitive deficits, motor incoordination and histopathological changes such as astrocyte swelling and vacuolization; hallmarks in HE, via reducing hyperammonemia, ameliorating hepatic function, in addition to its anti-oxidant, inactivation of TLR-4/NF-κB inflammatory pathway, and anti-apoptotic effects.

Keywords: chrysin, hepatic encephalopathy, oxidative stress, rats, thioacetamide, TLR4/NF-κB pathway

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Authors: Yun-Tao Zhang, Jong-Yeop Bae, Whoi-Yul Kim

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Background modeling and subtraction in video analysis has been widely proved to be an effective method for moving objects detection in many computer vision applications. Over the past years, a large number of approaches have been developed to tackle different types of challenges in this field. However, the dynamic background and illumination variations are two of the most frequently occurring issues in the practical situation. This paper presents a new two-layer model based on codebook algorithm incorporated with local binary pattern (LBP) texture measure, targeted for handling dynamic background and illumination variation problems. More specifically, the first layer is designed by block-based codebook combining with LBP histogram and mean values of RGB color channels. Because of the invariance of the LBP features with respect to monotonic gray-scale changes, this layer can produce block-wise detection results with considerable tolerance of illumination variations. The pixel-based codebook is employed to reinforce the precision from the outputs of the first layer which is to eliminate false positives further. As a result, the proposed approach can greatly promote the accuracy under the circumstances of dynamic background and illumination changes. Experimental results on several popular background subtraction datasets demonstrate a very competitive performance compared to previous models.

Keywords: background subtraction, codebook model, local binary pattern, dynamic background, illumination change

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Authors: Julie V. Logan, Preston T. Webster, Kevin B. Woller, Christian P. Morath, Michael P. Short

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Semiconductors, as the base of critical electronic systems, are exposed to damaging radiation while operating in space, nuclear reactors, and particle accelerator environments. What innate property allows some semiconductors to sustain little damage while others accumulate defects rapidly with dose is, at present, poorly understood. This limits the extent to which radiation tolerance can be implemented as a design criterion. To address this problem of determining the driver of semiconductor radiation tolerance, the first step is to generate a dataset of the relative radiation tolerance of a large range of semiconductors (exposed to the same radiation damage and characterized in the same way). To accomplish this, Rutherford backscatter channeling experiments are used to compare the displaced lattice atom buildup in InAs, InP, GaP, GaN, ZnO, MgO, and Si as a function of step-wise alpha particle dose. With this experimental information on radiation-induced incorporation of interstitial defects in hand, hybrid density functional theory electron densities (and their derived quantities) are calculated, and their gradient and Laplacian are evaluated to obtain key fundamental information about the interactions in each material. It is shown that simple, undifferentiated values (which are typically used to describe bond strength) are insufficient to predict radiation tolerance. Instead, the curvature of the electron density at bond critical points provides a measure of radiation tolerance consistent with the experimental results obtained. This curvature and associated forces surrounding bond critical points disfavors localization of displaced lattice atoms at these points, favoring their diffusion toward perfect lattice positions. With this criterion to predict radiation tolerance, simple density functional theory simulations can be conducted on potential new materials to gain insight into how they may operate in demanding high radiation environments.

Keywords: density functional theory, GaN, GaP, InAs, InP, MgO, radiation tolerance, rutherford backscatter channeling

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Authors: S. Valarmathi, P. B. Harathi, R. Sridhar, S. Balasubramanian

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Machine learning tools in medical diagnosis is increasing due to the improved effectiveness of classification and recognition systems to help medical experts in diagnosing breast cancer. In this study, ID3 chooses the splitting attribute with the highest gain in information, where gain is defined as the difference between before the split versus after the split. It is applied for age, location, taluk, stage, year, period, martial status, treatment, heredity, sex, and habitat against Very Serious (VS), Very Serious Moderate (VSM), Serious (S) and Not Serious (NS) to calculate the gain of information. The ranked histogram gives the gain of each field for the breast cancer data. The doctors use TNM staging which will decide the risk level of the breast cancer and play an important decision making field in fuzzy logic for perception based measurement. Spatial risk area (taluk) of the breast cancer is calculated. Result clearly states that Coimbatore (North and South) was found to be risk region to the breast cancer than other areas at 20% criteria. Weighted value of taluk was compared with criterion value and integrated with Map Object to visualize the results. ID3 algorithm shows the high breast cancer risk regions in the study area. The study has outlined, discussed and resolved the algorithms, techniques / methods adopted through soft computing methodology like ID3 algorithm for prognostic decision making in the seriousness of the breast cancer.

Keywords: ID3 algorithm, breast cancer, fuzzy logic, MATLAB

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Authors: Navven Desai, Veena Soraganvi

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Heavy metals such as lead, cadmium and mercury do not have biological significance hence they are known to be extremely toxic heavy metals. Water contains various heavy metals like Cadmium (Cd), Chromium (Cr), Copper (Cu), Nickel (Ni), Arsenic (As), Lead (Pb), and Zinc (Zn) etc., when it gets polluted with industrial waste water. These heavy metals cause various health effects even at low concentration when consumed by humans. Most of the heavy metals are poisonous to living organisms. Heavy metals are non-degradable and are preserved in the environment through bioaccumulation. Therefore removal of heavy metals from water is necessary. In recent years, a great deal of attentions has been focused on to the application of nanosized metal oxides to treat heavy metals, especially titanium oxides, ferric oxides, manganese oxides, aluminium oxides and magnesium oxides as adsorbent and photocatalyst. TiO2 based photocatalysts have attracted continuously increasing attention because of the excellent properties such as high light -conversion efficiency, chemical stability, nontoxic nature, low cost. The catalyst displays high photocatalytic activity because of its large surface area. In this study, the photocatalytic degradation of Lead (Pb) from aqueous solution was investigated in natural sunlight by using TiO2 as Nanomaterial. This study was performed at laboratory scale. All the experiments were carried out in the batch process. The concentration of lead was constant (25mg/lit) in the experiment and effect of titanium dioxide dose and pH were varied to study the removal efficiency of the lead by adsorption. Further study was performed on the dependence of photocatalytic reaction on the reaction temperature. The aqueous solution was prepared by Lead metal powder. TiO2 photo catalyst nanopowder used was Sisco-74629 grade. The heavy metal is analyzed with VARIAN AA 240 atomic adsorption spectrophotometer. The study shows, with increasing TiO2 dose and pH the lead removal increases. According to study, it can be concluded that the utilization of titanium dioxide accounted for higher efficiency in the removal of lead from aqueous solution.

Keywords: adsorption, heavy metals, nanomaterial, photocatalysis

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Authors: Rajesh Kumar Suman, Ipseeta Ray Mohanty, Manjusha K. Borde, Ujjawala maheswari, Y. A. Deshmukh

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Background: Metabolic syndrome encompasses cluster of risk factors for cardiovascular disease which includes abdominal obesity, dyslipidemia, hypertension, and hyperglycemia. The incidence of metabolic syndrome is on the rise globally. Objective: The present study was designed to develop a unique animal model that will mimic the pathological features seen in a large pool of individuals with diabetes and metabolic syndrome; suitable for pharmacological screening of drugs beneficial in this condition. Material and Methods: A combination of high fat diet (HFD) and low dose of streptozotocin (STZ) at 30, 35 and 40 mg/kg was used to induce metabolic syndrome co-existing with diabetes mellitus in Wistar rats. Results: The 40 mg/kg STZ produced sustained hyperglycemia and the dose was thus selected for our study to induce diabetes mellitus. Rat fed HFD (HF-DC) group showed significant (p < 0.001) increase in body weight on 4th and 7th week as compared with NC (Normal Control) group rats. However, the increase in body weight of HF-DC group rats was not sustained at the end of 10th weeks. Various components of metabolic syndrome such as dyslipidemia {(Increased Triglyceride, total Cholesterol, LDL Cholesterol and decreased HDL Cholesterol)}, diabetes mellitus (Blood Glucose, HbA1c, Serum Insulin, C-peptide), hypertension {Systolic Blood pressure (p < 0.001)} were mimicked in the developed model of metabolic syndrome co existing with diabetes mellitus. In addition significant cardiac injury as indicated by CPK-MB levels, artherogenic index, hs-CRP. The decline in hepatic function {(p < 0.01) increase in the level of SGPT (U/L)} and renal function {(increase in creatinine levels (p < 0.01)} when compared to NC group rats. The histopathological assessment confirmed presence of edema, necrosis and inflammation in Heart, Pancreas, Liver and Kidney of HFD-DC group as compared to NC. Conclusion: The present study has developed a unique rodent model of metabolic syndrome; with diabetes as an essential component.

Keywords: diabetes, metabolic syndrome, high fat diet, streptozotocin, rats

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Authors: Miroslava Markovic, Snezana Rajkovic, Ljubinko Rakonjac, Aleksandar Lucic

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Oak powdery mildew is a serious problem on seedlings in nurseries as well as on naturally and artificially introduced progeny. The experiments were set on oak seedlings in two nurseries located in Central Serbia, where control of oak powdery mildew Microsphaera alphitoides Griff. et Maubl. had been conducted through alternative protection measures by means of various dosages of AQ-10 biofungicide, with and without added polymer (which has so far never been used in this country for control of oak powdery mildew). Simultaneous testing was conducted on the efficiency of a chemical sulphur-based preparation (used in this area for many years as a measure of suppression of powdery mildews, without the possibility of developing resistance of the pathogen to the active matter). To date, the Republic of Serbia has registered no fungicides for suppression of pathogens in the forest ecosystems. In order to introduce proper use of new disease-fighting agents into a country, certain relevant principles, requirements and criteria prescribed by the Forest Stewardship Council (FSC) must be observed, primarily with respect to measures of assessment and mitigation of risks, the list of dangerous and highly dangerous pesticides with the possibility of alternative protection. One of the main goals of the research was adjustment of the protective measures to the FSC policy through selection of eco-toxicologically favourable fungicides, given the fact that only preparations named on the list of permitted active matters are approved for use in certified forests. The results of the research have demonstrated that AQ-10 biofungicide can be used as a part of integrated disease management programmes as an alternative, through application of several treatments during vegetation and combination with other active matters registered for these purposes, so as to curtail the use of standard fungicides for control of powdery mildews on oak seedlings in nurseries. The best results in suppression of oak powdery mildew were attained through use of AQ-10 biofungicide (dose 50 or 70g/ha) with added polymer Nu Film-17 (dose 1.0 or 1.5 l/ha). If the treatment is applied at the appropriate time, even fewer number of treatments and smaller doses will be just as efficient.

Keywords: oak powdery mildew, biofungicides, polymers, Microsphaera alphitoides

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Authors: Liyun Chang, Cheng-Hsiang Tsai

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To ensure the radiation precisely delivering to the target of cancer patients, the linear accelerator equipped with the pretreatment on-board imaging system is introduced and through it the patient setup is verified before the daily treatment. New generation radiotherapy using beam-intensity modulation, usually associated the treatment with steep dose gradients, claimed to have achieved both a higher degree of dose conformation in the targets and a further reduction of toxicity in normal tissues. However, this benefit is counterproductive if the beam is delivered imprecisely. To avoid shooting critical organs or normal tissues rather than the target, it is very important to carry out the quality assurance (QA) of this on-board imaging system. The QA of the On-Board Imager® (OBI) system of one Varian Clinac-iX linear accelerator was performed through our procedures modified from a relevant report and AAPM TG142. Two image modalities, 2D radiography and 3D cone-beam computed tomography (CBCT), of the OBI system were examined. The daily and monthly QA was executed for five months in the categories of safety, geometrical accuracy and image quality. A marker phantom and a blade calibration plate were used for the QA of geometrical accuracy, while the Leeds phantom and Catphan 504 phantom were used in the QA of radiographic and CBCT image quality, respectively. The reference images were generated through a GE LightSpeed CT simulator with an ADAC Pinnacle treatment planning system. Finally, the image quality was analyzed via an OsiriX medical imaging system. For the geometrical accuracy test, the average deviations of the OBI isocenter in each direction are less than 0.6 mm with uncertainties less than 0.2 mm, while all the other items have the displacements less than 1 mm. For radiographic image quality, the spatial resolution is 1.6 lp/cm with contrasts less than 2.2%. The spatial resolution, low contrast, and HU homogenous of CBCT are larger than 6 lp/cm, less than 1% and within 20 HU, respectively. All tests are within the criteria, except the HU value of Teflon measured with the full fan mode exceeding the suggested value that could be due to itself high HU value and needed to be rechecked. The OBI system in our facility was then demonstrated to be reliable with stable image quality. The QA of OBI system is really necessary to achieve the best treatment for a patient.

Keywords: CBCT, image quality, quality assurance, OBI

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Authors: R. Fardid, R. Coppes

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Introduction: In mediastinal radiotherapy and to a lesser extend also in total-body irradiation (TBI) radiation exposure may lead to development of cardiac diseases. Radiation-induced heart disease is dose-dependent and it is characterized by a loss of cardiac function, associated with progressive heart cells degeneration. We aimed to determine the in-vivo radiation effects on fibronectin, ColaA1, ColaA2, galectin and TGFb1 gene expression levels in left ventricle heart tissues of rats after irradiation. Material and method: Four non-treatment adult Wistar rats as control group (group A) were selected. In group B, 4 adult Wistar rats irradiated to 20 Gy single dose of 150 Mev proton beam locally in heart only. In heart plus lung irradiate group (group C) 4 adult rats was irradiated by 50% of lung laterally plus heart radiation that mentioned in before group. At 8 weeks after radiation animals sacrificed and left ventricle heart dropped in liquid nitrogen for RNA extraction by Absolutely RNA® Miniprep Kit (Stratagen, Cat no. 400800). cDNA was synthesized using M-MLV reverse transcriptase (Life Technologies, Cat no. 28025-013). We used Bio-Rad machine (Bio Rad iQ5 Real Time PCR) for QPCR testing by relative standard curve method. Results: We found that gene expression of fibronectin in group C significantly increased compared to control group, but it was not showed significant change in group B compared to group A. The levels of gene expressions of Cola1 and Cola2 in mRNA did not show any significant changes between normal and radiation groups. Changes of expression of galectin target significantly increased only in group C compared to group A. TGFb1 expressions in group C more than group B showed significant enhancement compared to group A. Conclusion: In summary we can say that 20 Gy of proton exposure of heart tissue may lead to detectable damages in heart cells and may distribute function of them as a component of heart tissue structure in molecular level.

Keywords: gene expression, heart damage, proton irradiation, radiotherapy

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Authors: Sanjay Singh, Karunanithi Priyanka, Ramoji Kosuru, Raju Prasad Sharma

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Herbal drugs are well known for their mixed pharmacological activities with the benefit of no harmful side effects. The use of herbal drugs is limited because of their higher dose requirement, frequent drug administration, poor bioavailability of phytochemicals and delayed onset of action. Ficus religiosa, a potent anti-oxidant plant useful in the treatment of diabetes and cancer was selected for the study. Solid lipid nanoparticles (SLN) of Ficus religiosa extract was developed for the enhancement in oral bioavailability of stigmasterol and β-sitosterol-d-glucoside, principal components present in the extract. Hot homogenization followed by ultrasonication method was used to develop extract loaded SLN. Developed extract loaded SLN were characterized for particle size, PDI, zeta potential, entrapment efficiency, in vitro drug release and kinetics, fourier transform infra-red spectroscopy, differential scanning calorimetry, powder X-ray diffractrometry and stability studies. Entrapment efficiency of optimized extract loaded SLN was found to be 68.46 % (56.13 % of stigmasterol and 12.33 % of β-sitosteryl-d-glucoside, respectively). RP HPLC method development was done for simultaneous estimation of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract in rat plasma. Bioavailability studies were carried out for extract in suspension form and optimized extract loaded SLN. AUC of stigmasterol and β-sitosterol-d-glucoside were increased by 6.7-folds by 9.2-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Also, Cmax of stigmasterol and β-sitosterol-d-glucoside were increased by 4.3-folds by 3.9-folds, respectively in rats treated with extract loaded SLN compared to extract suspension. Mean residence times (MRT) for stigmasterol were found to be 12.3 ± 0.67 hours from extract and 7.4 ± 2.1 hours from SLN and for β-sitosterol-d-glucoside, 10.49 ± 2.9 hours from extract and 6.4 ± 0.3 hours from SLN. Hence, it was concluded that SLN enhanced the bioavailability and reduced the MRT of stigmasterol and β-sitosterol-d-glucoside in Ficus religiosa extract which in turn may lead to reduction in dose of Ficus religiosa extract, prolonged duration of action and also enhanced therapeutic efficacy.

Keywords: Ficus religiosa, phytosterolins, bioavailability, solid lipid nanoparticles, stigmasterol and β-sitosteryl-d-glucoside

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Authors: P. B. Sob, A. A. Alugongo, T. B. Tengen

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The activation volume of 6082T6 aluminum is investigated at different temperatures on grain size variants. The deformation activation volume was computed on the basis of the relationship between the Boltzmann’s constant k, the testing temperatures, the material strain rate sensitivity and the material yield stress of grain size variants. The material strain rate sensitivity is computed as a function of yield stress and strain rate of grain size variants. The effect of the material strain rate sensitivity and the deformation activation volume of 6082T6 aluminum at different temperatures of 3-D grain are discussed. It is shown that the strain rate sensitivities and activation volume are negative for the grain size variants during the deformation of nanostructured materials. It is also observed that the activation volume vary in different ways with the equivalent radius, semi minor axis radius, semi major axis radius and major axis radius. From the obtained results it is shown that the variation of activation volume increased and decreased with the testing temperature. It was revealed that, increased in strain rate sensitivity led to decrease in activation volume whereas increased in activation volume led to decrease in strain rate sensitivity.

Keywords: nanostructured materials, grain size variants, temperature, yield stress, strain rate sensitivity, activation volume

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Authors: Marilia M. Camargo, Luisa A. Gachet-Barbosa, Rosa C. C. Lintz

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The addition of fibers into concrete matrix can enhance some properties of the composite, such as tensile, flexural and impact strengths, toughness, deformation capacity and post-cracking ductility. Many factors affect the mechanical behavior of fiber reinforced concrete, such as concrete matrix (concrete strength, additions, aggregate diameter, etc.), characteristics of the fiber (geometry, type, aspect ratio, volume, orientation, distribution, strength, stiffness, etc.), specimen (size, geometry, method of preparation and loading rate). This research investigates the effects of fiber volume and orientation on the post-cracking behavior of steel fiber reinforced concrete (SFRC). Hooked-end steel fibers with aspect ratios of 45 were added into concrete with volume of 0,32%, 0,64%, 0,94%. The post-cracking behaviour was assessed by double punch test of cubic specimens and the actual volume and orientation of the fibers were determined by non-destructive tests by means of electromagnetic induction. The results showed that the actual volume of fibers in each sample differs in a small amount from the dosed volume of fibers and that the deformation and toughness of the concrete increase with the increase in the actual volume of fibers. In determining the orientation of the fibers, it was found that they tend to distribute more in the X and Y axes due to the influence of the walls of the mold. In addition, it was concluded that the orientation of the fibers is important in the post-cracking behaviour of FRC when analyzed together with the actual volume of fibers, since the greater the volume of fibers, the greater the number of fibers oriented orthogonally to the application of loadings and, consequently, there is a better mechanical behavior of the composite. These results provide a better understanding of the influence of volume and fiber orientation on the post-cracking behavior of the FRC.

Keywords: fiber reinforced concrete, steel fibers, volume of fibers, orientation of fibers, post-cracking behaviour

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Authors: Zahid Manzoor, Shaukat Hussain Munawar, Zahid Iqbal, Imran Ahmad Khan, Abdul Aziz, Hafiz Muhammad Qasim

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The present study was aimed to investigate the pharmacokinetics behavior and optimal dosage regimen of danofloxacin in 8 adult healthy buffaloes of local breed (Nili Ravi) following single intravenous administration at the dose of 2.5 mg/kg body weight. Plasma drug concentrations at various time intervals were measured by HPLC method. In vitro plasma protein binding was determined employing the ultrafiltration technique. The distribution and elimination of danofloxacin was rapid, as indicated by the values (Mean±SD) of distribution half-life (t1/2α = 0.25±0.09 hours) and elimination half life (t1/2β = 3.26±0.43 hours), respectively. Volume of distribution at steady state (Vss) was 1.14±0.12 L/kg, displaying its extensive distribution into various body fluids and tissues. The high value of AUC (9.80±2.14 µg/ml.hr) reflected the vast area of the body covered by drug concentration. The mean residence time was noted to be 4.78±0.52 hours. On the basis of pharmacokinetic parameters, a suitable intravenous regimen for danofloxacin in adult buffaloes would be 6.5 mg/kg to be repeated after 12 hours intervals. The present study is the foremost pharmacokinetic study of danofloxacin in the local species which would provide the valueable contribution in the local manufacturing of danofloxacin in Pakistan in future.

Keywords: danofloxacin, pharmacokinetics, plasma protein binding, buffaloes, dosage regimen

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Authors: Maria Altamirano, Alfonso Duran

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Biostimulation has recently become important in order to improve the stability and performance of the anaerobic digestion (AD) process. This strategy involves the addition of nutrients or supplements to improve the rate of degradation of a native microbial consortium. With the aim of biostimulate sytrophism between secondary fermenting bacteria and methanogenic archaea, improving metabolite degradation and efficient conversion to methane, the addition of conductive materials, mainly carbon based have been studied. This research seeks to highlight the effect that coconut biochar (CBC) has on the metanogenic conversion of the organic fraction of municipal solid waste (OFMSW), analyzing the surface chemistry properties that give biochar its capacity to serve as a redox mediator in the anaerobic digestion process. The biochar characterization techniques were electrical conductivity (EC) scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), Fourier Transform Infrared Transmission Spectroscopy (FTIR) and Cyclic Voltammetry (CV). Effect of coconut biochar addition was studied using Authomatic Methane Potential Test System (AMPTS II) applying a one-way variance analysis to determine the dose that leads to higher methane performance. The surface chemistry of the CBC could confer properties that enhance the AD process, such as the presence of alkaline and alkaline earth metals and their hydrophobicity that may be related to their buffering capacity and the adsorption of polar and non-polar compounds, such as NH4+ and CO2. It also has aromatic functional groups, just as quinones, whose potential as a redox mediator has been demonstrated and its morphology allows it to form an immobilizing matrix that favors a closer activity among the syntrophic microorganisms, which directly contributed in the oxidation of secondary metabolites and the final reduction to methane, whose yield is increased by 39% compared to controls, with a CBC dose of 1 g/L.

Keywords: anaerobic digestion, biochar, biostimulation, syntrophic metabolism

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Authors: R. Kandiah, K. Miyamoto

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In Sri Lanka, the Jaffna area is a high drought affected area and depends mainly on groundwater aquifers for water needs. Water for daily activities is extracted from wells. As households manually extract water from the wells, it is not drawn from mid evening to early morning. The water inflow at night provides the maximum water level that decreases during the daytime due to extraction. The storage volume of water in wells is limited or at its lowest level during the dry season. This study analyzes the domestic water budget during the dry season in the Jaffna area. In order to evaluate the water inflow rate into wells, storage volume and extraction volume from wells over time, water pressure is measured at the bottom of three wells, which are located in coastal area denoted as well A, in nonspecific area denoted as well B, and agricultural area denoted as well C. The water quality at the wells A, B, and C, are mostly fresh, modest fresh, and saline respectively. From the monitoring, we can find that the daily inflow amount of water into the wells and daily water extraction depend on each other, that is, higher extraction yields higher inflow. And, in the dry season, the daily inflow volume and the daily extraction volume of each well are almost in balance.

Keywords: accessible volume, consumption volume, inflow rate, water budget

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Authors: Benlaifa Meriem, Berredjem Hajira, Bouasla Radia, Berredjem Malika, Djebar Med Reda

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Toxoplasmosis is a cosmopolitan infection due to Toxoplasma gondii (T.gondii). It is a significant cause of congenital disease and an important opportunistic pathogen which has become a worldwide increasing problem due to the AIDS epidemic. Current available drugs do not give satisfactory results and often have only a static and several adverse side effects as it is the case of pyrimethamine. So, the need to develop and evaluate new drugs is critical. The purpose of this study is to investigate the in vitro and in vivo effects of the new chiral N-acylsulfonamide bis-oxazolidin-2-ones on T.gondii. In this study, anti-T.gondii RH strain activities, of two new chiral N-acylsulfonamide bis-oxazolidin-2-ones were evaluated in vitro, using a MRC-5 fibroblast tissue cultures to determine the concentration that inhibit parasite multiplication by 50% (IC50) of each drug and in vivo, by PCR detection of the tachyzoites in mice ascites after new molecules treatment, using the 35-fold repetitive B1 gene of T.gondii. The in vitro results demonstrated that the treatment with the tested molecules decreased the amount of tachyzoites in cell culture in a dose-dependent manner. The inhibition was complete for concentrations over 4 mg/ml. The IC50 of Mol 1 and Mol 2 were 1.5 and 3 mg/ml, respectively, and were quite similar to the control one (2 mg/ml). The Mol 1 was highly active against T.gondii in cell cultures than Mol 2; these results were similar to those of sulfadiazine-treated group (p < 0.05). Toxoplasma-specific DNA was demonstrated in all ascites samples from infected mice of the different tested groups. Mol 1 showed better effect than Mol 2, but it did not completely inhibit the parasite proliferation. The intensity of amplification products increased when the treatment started late after infection. These findings suggest continuous parasite replication despite the treatment. In conclusion, our results showed a promising treatment effect of the tested molecules and suggest that in vitro, the Mol 1, and Mol 2 have a dose-dependent effect and a high cytotoxicity on the studied cells. The present study revealed that concentration and duration of tested molecules treatment are major factors that influence the course of Toxoplasma infection in infected mice.

Keywords: cytotoxicity, PCR, sulfonamide, Toxoplasma gondii

Procedia PDF Downloads 504