Search results for: time of release

Authors: Animesh Pan, Geoffrey D. Bothun

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With the development of nanotechnology, research in multifunctional delivery systems has a new pace and dimension. An incipient challenge is to design an all-in-one delivery system that can be used for multiple purposes, including tumor targeting therapy, radio-frequency (RF-), near-infrared (NIR-), light-, or pH-induced controlled release, photothermal therapy (PTT), photodynamic therapy (PDT), and medical diagnosis. In this regard, various inorganic nanoparticles (NPs) are known to show great potential as the 'functional components' because of their fascinating and tunable physicochemical properties and the possibility of multiple theranostic modalities from individual NPs. Magnetic, luminescent, and plasmonic properties are the three most extensively studied and, more importantly biomedically exploitable properties of inorganic NPs. Although successful attempts of combining any two of them above mentioned functionalities have been made, integrating them in one system has remained challenge. Keeping those in mind, controlled designs of complex colloidal nanoparticle system are one of the most significant challenges in nanoscience and nanotechnology. Therefore, systematic and planned studies providing better revelation are demanded. We report a multifunctional delivery platform-based liposome loaded with drug, iron-oxide magnetic nanoparticles (MNPs), and a gold shell on the surface of liposomes, were synthesized using a lipid with polyelectrolyte (layersomes) templating technique. MNPs and the anti-cancer drug doxorubicin (DOX) were co-encapsulated inside liposomes composed by zwitterionic phophatidylcholine and anionic phosphatidylglycerol using reverse phase evaporation (REV) method. The liposomes were coated with positively charge polyelectrolyte (poly-L-lysine) to enrich the interface with gold anion, exposed to a reducing agent to form a gold nanoshell, and then capped with thio-terminated polyethylene glycol (SH-PEG2000). The core-shell nanostructures were characterized by different techniques like; UV-Vis/NIR scanning spectrophotometer, dynamic light scattering (DLS), transmission electron microscope (TEM). This multifunctional system achieves a variety of functions, such as radiofrequency (RF)-triggered release, chemo-hyperthermia, and NIR laser-triggered for photothermal therapy. Herein, we highlight some of the remaining major design challenges in combination with preliminary studies assessing therapeutic objectives. We demonstrate an efficient loading and delivery system to significant cell death of human cancer cells (A549) with therapeutic capabilities. Coupled with RF and NIR excitation to the doxorubicin-loaded core-shell nanostructure helped in securing targeted and controlled drug release to the cancer cells. The present core-shell multifunctional system with their multimodal imaging and therapeutic capabilities would be eminent candidates for cancer theranostics.

Keywords: cancer thernostics, multifunctional nanostructure, photothermal therapy, radiofrequency targeting

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Authors: Mohit Wadhawan, Sushma Rathaur

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Lymphatic filariasis, also called elephantiasis is a tropical disease afflicting over 120 million people in 81 countries worldwide. Existing anti filarial drugs are effective against the larval stages of filarial parasites which call for an urgent need of drugs which are macrofilaricidal. Identification of molecular targets crucial for survival of filarial parasites is a prerequisite for drug designing. Prolyl oligopeptidase (POP) is one such crucial enzyme involved in the maturation and degradation of neuropeptides and peptide hormones. We have identified this peptidase in the bovine filarial parasite, Setaria cervi. Effect of inhibition of POP on the proteome profile of filarial parasite has been discussed in this study. Filarial parasites were exposed to Z-pro-prolinal (ZPP), a specific POP inhibitor for 8 h and the motility and viability of the parasites was observed. It significantly reduced the motility and viability of the parasites. To study the proteome profile, the cytosolic, endoplasmic reticulum (ER) and mitochondrial extracts of the adult female parasites were subjected to 2-dimensional electrophoresis. As analyzed by the PD-Quest software, the ZPP caused the alteration in the different subcellular proteins, and the significantly altered proteins were identified using MALDI-MS/MS spectrometry. The major proteins identified were found to play important role in diverse biological functions like signaling, redox regulation, energy metabolism, stress response, and cytoskeleton formation. Moreover, we found upregulation in the calcium binding proteins such as calreticulin, calponin, and calpain-6 suggesting that POP inhibition regulates calcium release. This relates to earlier reports that POP plays non-catalytic role in inositol 1,4,5-trisphosphate (IP3) signaling inducing release of calcium from ER. Taken together, the data demonstrated that inhibition of prolyl oligopeptidase alter the overall proteome signifying its role in survival of the filarial parasites. Thus this study provides a basis for the use of POP as a chemotherapeutic target for the treatment of lymphatic filariasis.

Keywords: lymphatic filariasis, setaria cervi, prolyl oligopeptidase, proteomics

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Authors: Jamuna Konda, Umamaheswara Reddy Karumuri, Sriramya Muthugi, Varun Pishati, Ravi Shakya,

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This paper investigates the challenges involved in mathematical modeling of plant simulation models ensuring the performance of the plant models much closer to the real time physical model. The paper includes the analysis performed and investigation on different methods of modeling, design and development for plant model. Issues which impact the design time, model accuracy as real time model, tool dependence are analyzed. The real time hardware plant would be a combination of multiple physical models. It is more challenging to test the complete system with all possible test scenarios. There are possibilities of failure or damage of the system due to any unwanted test execution on real time.

Keywords: model based design (MBD), MATLAB, Simulink, stateflow, plant model, real time model, real-time workshop (RTW), target language compiler (TLC)

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Authors: Yasmin Begum Mohammed

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Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

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Authors: Rawia M. Khalil, Ahmed A. Abd El Rahman, Mahfouz A. Kassem, Mohamed S. El Ridi, Mona M. Abou Samra, Ghada E. A. Awad, Soheir S. Mansy

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Solid lipid nanoparticles (SLNs) have gained great attention for the topical treatment of skin associated fungal infection as they facilitate the skin penetration of loaded drugs. Our work deals with the preparation of nystatin loaded solid lipid nanoparticles (NystSLNs) using the hot homogenization and ultrasonication method. The prepared NystSLNs were characterized in terms of entrapment efficiency, particle size, zeta potential, transmission electron microscopy, differential scanning calorimetry, rheological behavior and in vitro drug release. A stability study for 6 months was performed. A microbiological study was conducted in male rats infected with Candida albicans, by counting the colonies and examining the histopathological changes induced on the skin of infected rats. The results showed that SLNs dispersions are spherical in shape with particle size ranging from 83.26±11.33 to 955.04±1.09 nm. The entrapment efficiencies are ranging from 19.73±1.21 to 72.46±0.66% with zeta potential ranging from -18.9 to -38.8 mV and shear-thinning rheological Behavior. The stability studies done for 6 months showed that nystatin (Nyst) is a good candidate for topical SLN formulations. A least number of colony forming unit/ ml (cfu/ml) was recorded for the selected NystSLN compared to the drug solution and the commercial Nystatin® cream present in the market. It can be fulfilled from this work that SLNs provide a good skin targeting effect and may represent promising carrier for topical delivery of Nyst offering the sustained release and maintaining the localized effect, resulting in an effective treatment of cutaneous fungal infection.

Keywords: candida infections, hot homogenization, nystatin, solid lipid nanoparticles, stability, topical delivery

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Authors: Makda Aamir, Sood Aayushi, Syed Omar, Nihan Khuld, Iskander Peter, Ijaz Naeem, Sharma Nishant

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Introduction:Glycogen Storage Disease Type-1 (GSD-1) is a rare phenomenon primarily affecting the liver and kidney. Excessive accumulation of glycogen and fat in liver, kidney, and intestinal mucosa is noted in patients with deficiency of Glucose-6-phosphatase deficiency. Patients with GSD-1 have a wide spectrum of symptoms, including hepatomegaly, hypoglycemia, lactic acidemia, hyperlipidemia, hyperuricemia, and growth retardation. Age of onset, rate of disease progression and its severity is variable in this disease.Case:An 18-year-old male with GSD-1a, Von Gierke’s disease, hyperuricemia, and hypertension presented to the hospital with nausea and vomiting. The patient followed an hourly cornstarch regimen during the day and overnight through infusion via a PEG tube. The complaints started at work, where he was unable to tolerate oral cornstarch. He washemodynamically stable on arrival. ABG showed pH 7.372, PaCO2 30.3, and PaO2 92.2. WBC 16.80, K+ 5.8, HCO3 13, BUN 28, Cr 2.2, Glucose 60, AST 115, ALT 128, Cholesterol 352, Triglycerides >1000, Uric Acid 10.6, Lactic Acid 11.8 which trended down to 8.0. CT abdomen showed hepatomegaly and fatty infiltration with the PEG tube in place.He was admitted to the ICU and started on D5NS for hypoglycemia and lactic acidosis. Per request by the patient’s pediatrician, he was transitioned to IV D10/0.45NS at 110mL/Hr to maintain blood glucose above 75 mg/L. Frequent accuchecks were done till he could tolerate his dietary regimen with cornstarch. Lactic acid downtrend to 2.9, and accuchecks ranged between 100-110. Cr improved to 1.3, and his home medications (Allopurinol and Lisinopril) were resumed. He was discharged in stable condition with plans for further genetic therapy work up.Discussion:Mainstay therapy for Von Gierke’s Disease is the prevention of metabolic derangements for which dietary and lifestyle changes are recommended. A low fructose and sucrose diet is recommended by limiting the intake of galactose and lactose to one serving per day. Hypoglycemia treatment in such patients is two-fold, utilizing both quick and stable release sources. Cornstarch has been one such therapy since the 1980s; its slow digestion provides a steady release of glucose over a longer period of time as compared with other sources of carbohydrates. Dosing guidelines vary from age to age and person to person, but it is highly recommended to check BG levels frequently to maintain a BG > 70 mg/dL. Associated high levels of triglycerides and cholesterol can be treated with statins, fibrates, etc. Conclusion:The management of hypoglycemia in GSD 1 disease presents various obstacles which could prove to be fatal. Due to the deficiency of G6P, treatment with a specialized hypoglycemic regimen is warranted. A D10 ½ NS infusion can be used to maintain blood sugar levels as well as correct metabolic or lactate imbalances. Infusion should be gradually weaned off after the patient can tolerate oral feeds as this can help prevent the risk of hypoglycemia and other derangements. Further research is needed in regards to these patients for more sustainable regimens.

Keywords: von gierke, glycogen storage disease, hypoglycemia, genetic disease

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Authors: Mohan H., C. Elajchet Senni

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In the present of high energy consumption in every sphere of life, renewable energy sources are emerging as alternative to conventional fuels for energy security, mitigating green house gas emission and climate change. There has been a world wide interest in searching for alternatives to petroleum derived fuels due to their depletion as well as due to the concern for the environment. Vegetable oils have capability to solve this problem because they are renewable and lead to reduction in environmental pollution. But high smoke emission and lower thermal efficiency are the main problems associated with the use of neat vegetable oils in diesel engines. In the present work, performance, combustion and emission characteristics of CI engine fuelled with 20% by vol. methyl esters mixed with Karanja seed Oil, and Fuel injection pressures of 200 bar and 240 bar, injection timings (21°,23° and 25° BTDC) and Proportion B20 diesel respectively. Vegetable oils have capability to solve this problem because they are renewable and lead to reduction in environmental pollution. But, high smoke emission and lower thermal efficiency are the main problems associated with the use of neat vegetable oils in diesel engines. In the present work, performance, combustion and emission characteristics of CI engine fuelled with 20% by vol. methyl esters mixed with Karanja seed Oil, and Fuel injection pressures of 200 bar and 240 bar ,Injection timings (21°,23° and 25° BTDC) and Proportion B20 diesel respectively. Various performance, combustion and emission characteristics such as thermal efficiency, and brake specific fuel consumption, maximum cylinder pressure, instantaneous heat release, cumulative heat release with respect to crank angle, ignition lag, combustion duration, HC, NOx, CO, exhaust temperature and smoke intensity were measured.

Keywords: karanja oil, injection pressure, injection timing, karanja oil methyl ester

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Authors: Abdul Rahman Chamseddine

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Tawfiq al-Hakim remains one of the most prominent playwrights in his native in Egypt, and in the broader Arab world. His works, at the time of their release, drew international attention and acclaim. His first 1933 masterpiece Ahl al-Kahf (The People of the Cave) especially, garnered fame and recognition in both Europe and the Arab world. Borrowing its title from the Qur’anic Sura, al-Hakim’s play relays the untold story of the life of those 'three saints' after they wake up from their prolonged sleep. The playwright’s selection of topics upon which to base his works displays a deep appreciation of Arabic and Islamic heritage. Al-Hakim was clearly influenced by Islam, to such a degree that he wrote the biography of the Prophet Muhammad in 1936 very early in his career. Knowing that Al-Hakim was preceded by many poets and creative writers in writing the Prophet Muhammad’s biography. Notably like Al-Barudi, Ahmad Shawqi, Haykal, Al-‘Aqqad, and Taha Husayn who have had their own ways in expressing their views of the Prophet Muhammad. The attempt to understand the concern of all those renaissance men and others in the person of the Prophet would be indispensable in this study. This project will examine the reasons behind al-Hakim’s choice to draw upon these particular texts, embedded as they are in the context of Arabic and Islamic heritage, and how the use of traditional texts serves his contemporary goals. The project will also analyze the image of Islam in al-Hakim’s imagination. Elsewhere, he envisions letters or conversations between God and himself, which offers a window into understanding the powerful impact of the Divine on Tawfiq al-Hakim, one that informs his literature and merits further scholarly attention. His works occupying a major rank in Arabic literature, does not reveal Al-Hakim solely but the unquestioned assumptions operative in the life of his community, its mental make-up and its attitudes. Furthermore, studying the reception of works that touch on sensitive issues, like writing a letter to God, in Al-Hakim’s historical context would be of a great significance in the process of comprehending the mentality of the Muslim community at that time.

Keywords: Arabic language, Arabic literature, Arabic theology, modern Arabic literature

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Authors: Mohammad Zafar-ul Islam

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The breeding programme of Houbara bustard was started in Saudi Arabia in 1986 to undertake the restoration of native species such as Houbara through a programme of re-introduction, involving the release of captive-bred birds in the wild. Two sites were selected for houbara re-introduction, i.e., Mahazat as-Sayd and Saja Umm Ar-Rimth protected areas in 1988 and 1998 respectively. Both the areas are fenced fairly level, sandy plain with a few rock outcrops. Captive bred houbara have been released in Mahazat since 1992 by NWRC and those birds have been successfully breeding since then. The nesting season of the houbara at Mahazat recorded from February to May and on an average 20-25 nests are located each year but no nesting recorded in Saja. Houbara are monitored using radio transmitters through aerial tracking technique and also a vehicle for terrestrial tracking. Total population of houbara in Mahazat is roughly estimated around 300-400 birds, using the following: N = n1+n2+n3+n4+n5 (n1 = released or wild-born, radio, regularly monitored/checked; n2 = radio tagged missing; n3 = wild born chicks not recorded; n4 = wild born chicks, recorded but not tagged; n5 = immigrants). However, in Saja only 4-7 individuals of houbara have been survived since 2001 because most of the birds are predated immediately after the release. The mean annual home was also calculated using Kernel and Convex polygons methods with Range VII software. The minimum density of houbara was also calculated. In order to know the houbara movement or their migration to other regions, two captive-reared male houbara that were released into the wild and one wild born female were fitted with Platform Transmitter Terminals (PTT). The home range shows that wild-born female has larger movement than two males. More areas need to be selected for reintroduction programme to establish the network of sites to provide easy access to move these birds and mingle with the wild houbara. Some potential sites have been proposed which require more surveys to check the habitat suitability.

Keywords: re-introduction, survival rate, home range, Saudi Arabia

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Authors: Tsegaye Adane Birhan

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Recently, rapid industrialization has led to the excessive release of heavy metals such as Cr (VI) into the environment. Exposure to chromium (VI) can cause kidney and liver damage, depressed immune systems, and a variety of cancers. Therefore, treatment of Cr (VI) containing wastewater is mandatory. This study aims to optimize the removal of Cr (VI) from an aqueous solution using locally available Teff husk-activated carbon adsorbent. The laboratory-based study was conducted on the optimization of Cr (VI) removal efficiency of Teff husk-activated carbon from aqueous solution. A central composite design was used to examine the effect of the interaction of process parameters and to optimize the process using Design Expert version 7.0 software. The optimized removal efficiency of Teff husk activated carbon (95.597%) was achieved at 1.92 pH, 87.83mg/L initial concentration, 20.22g/L adsorbent dose and 2.07Hrs contact time. The adsorption of Cr (VI) on Teff husk-activated carbon was found to be best fitted with pseudo-second-order kinetics and Langmuir isotherm model of the adsorption. Teff husk-activated carbon can be used as an efficient adsorbent for the removal of chromium (VI) from contaminated water. Column adsorption needs to be studied in the future.

Keywords: batch adsorption, chromium (VI), teff husk activated carbon, response surface methodology, tannery wastewater

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Authors: Kamal Tolani, Sandeep Kumar, Rohit Luthra, Ankit Dadhania, Krishnaprasad K., Ram Gupta, Deepa Joshi

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Background: Post-operative analgesia remains a clinical challenge, with central and peripheral sensitization playing a pivotal role in treatment-related complications and impaired quality of life. Centrally acting opioids offer poor risk benefit profile with increased intensity of gastrointestinal or central side effects and slow onset of clinical analgesia. The objective of this study was to assess the clinical feasibility of induction and maintenance therapy with Tapentadol Nasal Spray (NS) in moderate to severe acute post-operative pain. Methods: Phase III, randomized, active-controlled, non-inferiority clinical trial involving 294 cases who had undergone surgical procedures under general anesthesia or regional anesthesia. Post-surgery patients were randomized to receive either Tapentadol NS 45 mg or Tramadol 100mg IV as a bolus and subsequent 50 mg or 100 mg dose over 2-3 minutes. The frequency of administration of NS was at every 4-6 hours. At the end of 24 hrs, patients in the tramadol group who had a pain intensity score of ≥4 were switched to oral tramadol immediate release 100mg capsule until the pain intensity score reduced to <4. All patients who had achieved pain intensity ≤ 4 were shifted to a lower dose of either Tapentadol NS 22.5 mg or oral Tramadol immediate release 50mg capsule. The statistical analysis plan was envisaged as a non-inferiority trial involving comparison with Tramadol for Pain intensity difference at 60 minutes (PID60min), Sum of Pain intensity difference at 60 minutes (SPID60min), and Physician Global Assessment at 24 hrs (PGA24 hrs). Results: The per-protocol analyses involved 255 hospitalized cases undergoing surgical procedures. The median age of patients was 38.0 years. For the primary efficacy variables, Tapentadol NS was non-inferior to Inj/Oral Tramadol in relief of moderate to severe post-operative pain. On the basis of SPID60min, no clinically significant difference was observed between Tapentadol NS and Tramadol IV (1.73±2.24 vs. 1.64± 1.92, -0.09 [95% CI, -0.43, 0.60]). In the co-primary endpoint PGA24hrs, Tapentadol NS was non–inferior to Tramadol IV (2.12 ± 0.707 vs. 2.02 ±0.704, - 0.11[95% CI, -0.07, 0.28). However, on further assessment at 48hr, 72 hrs, and 120hrs, clinically superior pain relief was observed with the Tapentadol NS formulation that was statistically significant (p <0.05) at each of the time intervals. Secondary efficacy measures, including the onset of clinical analgesia and TOTPAR, showed non-inferiority to Tramadol. The safety profile and need for rescue medication were also similar in both the groups during the treatment period. The most common concomitant medications were anti-bacterial (98.3%). Conclusion: Tapentadol NS is a clinically feasible option for improved compliance as induction and maintenance therapy while offering a sustained and persistent patient response that is clinically meaningful in post-surgical settings.

Keywords: tapentadol nasal spray, acute pain, tramadol, post-operative pain

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Authors: P. Narrima, C. Y. Looi, M. A. Mohd, H. M. Ali

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Persea declinata (Bl.) Kosterm is a member of the Lauraceae family, widely distributed in Southeast Asia. It is from the same genus with avocado (Persea americana Mill), which is widely consumed as food and for medicinal purposes. In the present study, we examined the anticancer properties of Persea declinata (Bl.) Kosterm bark methanolic crude extract (PDM). PDM exhibited a potent antiproliferative effect in MCF-7 human breast cancer cells, with an IC50 value of 16.68 µg/mL after 48h of treatment. We observed that PDM caused cell cycle arrest and subsequent apoptosis in MCF-7 cells, as exhibited by increased population at G0/G1 phase, higher lactate dehydrogenase (LDH) release, and DNA fragmentation. Mechanistic studies showed that PDM caused significant elevation in ROS production, leading to perturbation of mitochondrial membrane potential, cell permeability, and activation of caspases-3/7. On the other hand, real-time PCR and Western blot analysis showed that PDM treatment increased the expression of the proapoptotic molecule, Bax, but decreased the expression of prosurvival proteins, Bcl-2 and Bcl-xL, in a dose-dependent manner. These findings imply that PDM could inhibit proliferation in MCF-7 cells via cell cycle arrest and apoptosis induction, indicating its potential as a therapeutic agent worthy of further development.

Keywords: antiproliferative, apoptosis, MCF-7 human breast cancer, Persea declinata

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Authors: Victoria I. Michailova, Denitsa B. Momekova, Hristiana A. Velichkova, Evgeni H. Ivanov

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The aim of this work is to design and develop thermo-responsive nanosized drug delivery systems based on poly(N-isopropylacrylamide)-g-poly(ethylene oxide) (PNIPAM-g-PEO) double hydrophilic graft copolymers. The PNIPAM-g-PEO copolymers are able to self-assemble in water into nanoparticles above the LCST of the thermo-responsive PNIPAM backbone and to disassemble and rapidly release the entrapped drugs upon cooling. However, their drug delivery applications are often hindered by their low loading capacity as the drugs to be encapsulated do not dissolve in water. In order to overcome this limitation, here we applied a low-temperature procedure with ethanol as an alternative route to the formation and loading a model hydrophobic drug, Indomethacin (IMC), into PNIPAM-g-PEO nanoparticles. The rationale for this approach was that ethanol dissolves both IMC and the copolymer and its mixing with water may induce micellization of PNIPAM-g-PEO at temperatures lower than the LCST. The influence of the volume fraction of ethanol and the temperature on the aggregation characteristics of PNIPAM-g-PEO copolymers (2.7 mol% PEO) was investigated by means of DLS, TEM and rheological dynamic oscillatory tests. The studies showed rich phase behavior at T < LCST, incl. the formation of highly solvated 500-1000 nm complex structures, 30-70 nm micelles and polymersomes as well as giant polymersomes, as the fraction of added ethanol increased. We believe that the PNIPAM-g-PEO self-assembly is favored due to the different solvation of its constituting blocks in ethanol-water mixtures. The incorporation of IMC led to alteration of the physicochemical and morphological characteristics of the blank nanoparticles. In this case, only monodisperse polymersomes and micelles were observed in the solutions with an average diameter less than 65 nm and substantial drug loading (DLC ~117 – 146 wt%). Indomethacin release from the nanoparticles was responsive to temperature changes, being much faster at a temperature of 42oC compared to that of 37oC under otherwise the same conditions. The results obtained suggest that these PNIPAM-g-PEO nanoparticles could be potential in mild hyper-thermic delivery of nonsteroidal anti-inflammatory drugs.

Keywords: drug delivery, nanoparticles, poly(N-isopropylacryl amide)-g-poly(ethylene oxide), thermo-responsive

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Authors: Umut Tac, Leyla Tavacioglu, Pelin Bolat

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Human factor has been one of the elements that cause vulnerabilities which can be resulted with accidents in maritime transportation. When the roots of human factor based accidents are analyzed, gaps in performing cognitive abilities (reaction time, attention, memory…) are faced as the main reasons for the vulnerabilities in complex environment of maritime systems. Thus cognitive processes in maritime systems have arisen important subject that should be investigated comprehensively. At this point, neurocognitive tests such as reaction time analysis tests have been used as coherent tools that enable us to make valid assessments for cognitive status. In this respect, the aim of this study is to evaluate the reaction time (response time or latency) of seafarers due to their occupational experience and age. For this study, reaction time for different maneuverers has been taken while the participants were performing a sea voyage through a simulator which was run up with a certain scenario. After collecting the data for reaction time, a statistical analyze has been done to understand the relation between occupational experience and cognitive abilities.

Keywords: cognitive abilities, human factor, neurocognitive test battery, reaction time

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Authors: Amelia J. McFarland, Andrew K. Davey, Shailendra Anoopkumar-Dukie

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Microglia are the resident macrophage population of the central nervous system (CNS), contributing to both innate and adaptive immune response, and brain homeostasis. Activation of microglia occurs in response to a multitude of pathogenic stimuli in their microenvironment; this induces morphological and functional changes, resulting in a state of acute neuroinflammation which facilitates injury resolution. Adequate microglial function is essential for the health of the neuroparenchyma, with microglial dysfunction implicated in numerous CNS pathologies. Given the critical role that these macrophage-derived cells play in CNS homeostasis, there is a high demand for microglial models suitable for use in neuroscience research. The isolation of primary human microglia, however, is both difficult and costly, with microglial activation an unwanted but inevitable result of the extraction process. Consequently, there is a need for the development of alternative experimental models which exhibit morphological, biochemical and functional characteristics of human microglia without the difficulties associated with primary cell lines. In this study, our aim was to evaluate whether THP-1 human peripheral blood monocytes would display microglial-like qualities following an induced differentiation, and, therefore, be suitable for use as surrogate microglia. To achieve this aim, THP-1 human peripheral blood monocytes from acute monocytic leukaemia were differentiated with a range of phorbol 12-myristate 13-acetate (PMA) concentrations (50-200 nM) using two different protocols: a 5-day continuous PMA exposure or a 3-day continuous PMA exposure followed by a 5-day rest in normal media. In each protocol and at each PMA concentration, microglial-like cell morphology was assessed through crystal violet staining and the presence of CD-14 microglial / macrophage cell surface marker. Lipopolysaccharide (LPS) from Escherichia coli (055: B5) was then added at a range of concentrations from 0-10 mcg/mL to activate the PMA-differentiated THP-1 cells. Functional microglial-like behavior was evaluated by quantifying the release of prostaglandin (PG)-E2 and pro-inflammatory cytokines interleukin (IL)-1β and tumour necrosis factor (TNF)-α using mediator-specific ELISAs. Furthermore, production of global reactive oxygen species (ROS) and nitric oxide (NO) were determined fluorometrically using dichlorodihydrofluorescein diacetate (DCFH-DA) and diaminofluorescein diacetate (DAF-2-DA) respectively. Following PMA-treatment, it was observed both differentiation protocols resulted in cells displaying distinct microglial morphology from 10 nM PMA. Activation of differentiated cells using LPS significantly augmented IL-1β, TNF-α and PGE2 release at all LPS concentrations under both differentiation protocols. Similarly, a significant increase in DCFH-DA and DAF-2-DA fluorescence was observed, indicative of increases in ROS and NO production. For all endpoints, the 5-day continuous PMA treatment protocol yielded significantly higher mediator levels than the 3-day treatment and 5-day rest protocol. Our data, therefore, suggests that the differentiation of THP-1 human monocyte cells with PMA yields a homogenous microglial-like population which, following stimulation with LPS, undergo activation to release a range of pro-inflammatory mediators associated with microglial activation. Thus, the use of PMA-differentiated THP-1 cells represents a suitable microglial model for in vitro research.

Keywords: differentiation, lipopolysaccharide, microglia, monocyte, neuroscience, THP-1

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Authors: G. Lei, P. C. Dong, X. Q. Cen, S. Y. Mo

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One of the most significant parameters, describing the effect of water flooding in porous media, is flood-response time, and it is an important index in oilfield development. The responding time in low permeability reservoir is usually calculated by the method of stable state successive substitution neglecting the effect of medium deformation. Numerous studies show that the media deformation has an important impact on the development for low permeability reservoirs and can not be neglected. On the base of streamline tube model, we developed a method to interpret responding time with medium deformation factor. The results show that: the media deformation factor, threshold pressure gradient and well spacing have a significant effect on the flood response time. The greater the media deformation factor, threshold pressure gradient or well spacing is, the lower the flood response time is. The responding time of different streamlines varies. As the angle with the main streamline increases, the water flooding response time delays as a "parabola" shape.

Keywords: low permeability, flood-response time, threshold pressure gradient, medium deformation

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Authors: Ankit Agarwal

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Background: To develop a fully indigenous equipment which is an innovation in critical care, which can effectively scavenge contaminated ICU ventilator air. Objectives: Infection control in ICUs is a concern the world over. Various modalities from simple hand hygiene to costly antibiotics exist. However, one simple and scientific fact has been unnoticed till date, that the air exhaled by patients harboring MDR and other microorganisms, is released by ventilators into ICU atmosphere itself. This increases infection in ICU atmosphere and poses risk to other patients. Material and Methods: Some parts of the ventilator are neither disposable nor sterilizable. Over time, microorganisms accumulate in ventilator and act as a source of infection and also contaminate ICU air. This was demonstrated by exposing microbiological culture plates to air from expiratory port of ventilator, whereby dense growth of pathogenic microorganisms was observed. The present prototype of the equipment is totally self-made. It has a mechanism of controlled negative pressure, active and passive systems and various alarms and is versatile to be used with any ventilator. Results: This equipment captures the whole of contaminated exhaled air from the expiratory port of the ventilator and directs it out of the ICU space. Thus, it does not allow contaminated ventilator air to release into the ICU atmosphere. Therefore, there is no chance of exposure of other patients to contaminated air. Conclusion: The equipment is first of its kind the world over and is already under patent process. It has rightly been called ICU Ventilator Air Removal System (ICU VARS). It holds a chance that this technique will gain widespread acceptance shall find use in all the ventilators in most of the ICUs throughout the world.

Keywords: innovative, ICU Infection Control, microorganism, negative pressure

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Authors: Vineetha Bettaiah, Heggere S. Ranganath

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This paper presents a Hierarchical Piecewise Linear Approximation (HPLA) for the representation of time series data in which the time series is treated as a curve in the time-amplitude image space. The curve is partitioned into segments by choosing perceptually important points as break points. Each segment between adjacent break points is recursively partitioned into two segments at the best point or midpoint until the error between the approximating line and the original curve becomes less than a pre-specified threshold. The HPLA representation achieves dimensionality reduction while preserving prominent local features and general shape of time series. The representation permits course-fine processing at different levels of details, allows flexible definition of similarity based on mathematical measures or general time series shape, and supports time series data mining operations including query by content, clustering and classification based on whole or subsequence similarity.

Keywords: data mining, dimensionality reduction, piecewise linear representation, time series representation

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Authors: Ian Walmsley

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The aim of this paper is to explore the influence of time and temporality on the experience of coming off heroin in prison. The presentation draws on qualitative data collected during a small-scale pilot study of the role of self-care in the process of coming off drugs in prison. Time and temporality emerged as a key theme in the interview transcripts. Drug dependent prisoners experience of time in prison has not been recognized in the research literature. Instead, the literature on prison time typically views prisoners as a homogenous group or tends to focus on the influence of aging and gender on prison time. Furthermore, there is a tendency in the literature on prison drug treatment and recovery to conceptualize drug dependent prisoners as passive recipients of prison healthcare, rather than active agents. In building on these gaps, this paper argues that drug dependent prisoners experience multiple temporalities which involve an interaction between the body-times of the drug dependent prisoner and the economy of time in prison. One consequence of this interaction is the feeling that they are doing, at this point in their prison sentence, double prison time. The second part of the argument is that time and temporality were a means through which they governed their withdrawing bodies. In addition, this paper will comment on the challenges of prison research in England.

Keywords: heroin withdrawal, time and temporality, prison, body

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Authors: Sara Salehi, Ka Yu Cheng, Anna Heitz, Maneesha Ginige

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This study investigated the efficiency of granular sludge for phosphorous (P) recovery from wastewater. A laboratory scale sequencing batch reactor (SBR) was operated under alternating aerobic/anaerobic conditions to enrich a P accumulating granular biomass. This study showed that an overall 45-fold increase in P concentration could be achieved by reducing the volume of the P capturing liquor by 5-fold in the anaerobic P release phase. Moreover, different fractions of the granular biomass have different individual contributions towards generating a concentrated stream of P.

Keywords: granular sludge, PAOs, P recovery, SBR

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Authors: Nagmani Lnu

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Test automation is a vital requirement of any organization to release products faster to their customers. In most cases, an organization has an approach to developing automation but struggles to maintain it. It results in an increased number of Flaky Tests, reducing return on investments and stakeholders’ confidence. Challenges grow in multiple folds when automation is for UI behaviors. This paper describes the approaches taken to identify the root cause of automation instability in an extensive payments application and the best practices to address that using processes, tools, and technologies, resulting in a 75% reduction of effort.

Keywords: automation stability, test stability, Flaky Test, test quality, test automation quality

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Authors: A. Hakimiyan, H. Namazi

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Human behavior is defined as a range of behaviors exhibited by humans who are influenced by different internal or external sources. Human behavior is the subject of much research in different areas of psychology and neuroscience. Despite some advances in studies related to forecasting of human behavior, there are not many researches which consider the effect of the time delay between the presence of stimulus and the related human response. Analysis of EEG signal as a fractal time series is one of the major tools for studying the human behavior. In the other words, the human brain activity is reflected in his EEG signal. Artificial Neural Network has been proved useful in forecasting of different systems’ behavior especially in engineering areas. In this research, a time delay neural network is trained and tested in order to forecast the human EEG signal and subsequently human behavior. This neural network, by introducing a time delay, takes care of the lagging time between the occurrence of the stimulus and the rise of the subsequent action potential. The results of this study are useful not only for the fundamental understanding of human behavior forecasting, but shall be very useful in different areas of brain research such as seizure prediction.

Keywords: human behavior, EEG signal, time delay neural network, prediction, lagging time

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Authors: Syeda Kiran Shahzadi, Nasir Mahmood, Muhammad Abdul Qadir

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In the current research, three recombinant human interferon alpha-2b proteins (two modified and one normal form) were produced and Pegylated with an aim to produce more effective drugs against viral infections and cancers. The modified recombinant human interferon alpha-2b proteins were produced by site-directed modifications of interferon alpha 2b gene, targeting the amino acids at positions ‘R23’ and ‘H34’. The resulting chemically modified and unmodified forms of human interferon alpha 2b were conjugated with methoxy-polyethylene glycol propanealdehyde (400 KDa) and methoxy-polyethylene glycol succinimidyl succinate (400 KDa). Pegylation of normal and modified forms of Interferon alpha-2b prolong their release time and enhance their efficacy. The conjugation of PEG with modified and unmodified human interferon alpha 2b protein drugs was also characterized with 1H-NMR, HPLC, and SDS-PAGE. Antiproliferative assays of modified and unmodified forms of drugs were performed in cell based bioassays using MDBK cell lines. The results indicated that experimentally produced recombinant human interferon alpha-2b proteins were biologically active and resulted in significant inhibition of cell growth.

Keywords: protein refolding, antiproliferative activities, biomedical applications, human interferon alpha-2b, pegylation, mPEG-propionaldehyde, site directed mutagenesis, E. coli expression

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Authors: Imtisal-e-Noor, Andrew Martin, Olli Dahl

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Chemical Mechanical Polishing (CMP) has developed as a chosen planarization technique in nano-electronics industries for fabrication of the integrated circuits (ICs). These CMP processes release a huge amount of wastewater that contains oxides of nano-particles (silica, alumina, and ceria) and oxalic acid. Since, this wastewater has high solid content (TS), chemical oxygen demand (COD), and turbidity (NTU); therefore, in order to fulfill the environmental regulations, it needs to be treated up to the local and international standards. The present study proposed a unique CMP wastewater treatment method called Membrane Distillation (MD). MD is a non-isothermal membrane separation process, which allows only volatiles, i.e., water vapors to permeate through the membrane and provides 100% contaminants rejection. The performance of the MD technology is analyzed in terms of total organic carbon (TOC), turbidity, TS, COD, and residual oxide concentration in permeate/distilled water while considering different operating conditions (temperature, flow rate, and time). The results present that high-quality permeate has been recovered after removing 99% of the oxide particles and oxalic acid. The distilled water depicts turbidity < 1 NTU, TOC < 3 mg/L, TS < 50 mg/L, and COD < 100 mg/L. These findings clearly show that the MD treated water can be reused further in industrial processes or allowable to discharge in any water body under the stringent environmental regulations.

Keywords: chemical mechanical polishing, environmental regulations, membrane distillation, wastewater treatment

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Authors: Douglas MacCutcheon, Florian Pausch, Robert Ljung, Lorna Halliday, Stuart Rosen

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Contemporary classrooms are increasingly inclusive of children with mild to moderate disabilities and children from different language backgrounds (bilinguals, multilinguals), but classroom environments and standards have not yet been adapted adequately to meet these challenges brought about by this inclusivity. Additionally, classrooms are becoming noisier as a learner-centered as opposed to teacher-centered teaching paradigm is adopted, which prioritizes group work and peer-to-peer learning. Challenging listening conditions with distracting sound sources and background noise are known to have potentially negative effects on children, particularly those that are prone to struggle with speech perception in noise. Therefore, this research investigates two groups vulnerable to these environmental effects, namely children with a mild to moderate hearing loss (MMHLs) and sequential bilinguals learning in their second language. In the MMHL study, this group was assessed on speech-in-noise perception, and a number of receptive language and cognitive measures (auditory working memory, auditory attention) and correlations were evaluated. Speech reception thresholds were found to be predictive of language and cognitive ability, and the nature of correlations is discussed. In the bilinguals study, sequential bilingual children’s listening comprehension, speech-in-noise perception, listening effort and release from masking was evaluated under a number of different ecologically valid acoustic scenarios in order to pinpoint the extent of the ‘native language benefit’ for Swedish children learning in English, their second language. Scene manipulations included target-to-distractor ratios and introducing spatially separated noise. This research will contribute to the body of findings from which educational institutions can draw when designing or adapting educational environments in inclusive schools.

Keywords: sequential bilinguals, classroom acoustics, mild to moderate hearing loss, speech-in-noise, release from masking

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Authors: Kruti Jaruriya

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Distribution of arsenic (As) and its compound and related toxicology are serious concerns. This is particularly so since millions worldwide are suffering from toxicity due to drinking of As-contaminated groundwater. The Bengal delta plain, formed by the Ganga– Padma–Meghna–Brahmaputra river basin, covering several districts of West Bengal, India and Bangladesh is considered as the worst As affected alluvial basin. However, some equally affected, if not more, areas are emerging in upper Brahmaputra plains. The present study was carried out to examine As contamination trends in the worst affected part of Assam, India. Arsenic (As) mobilization to the groundwater of Brahmaputra floodplains was investigated in Titabor, Jorhat District, located in the North Eastern part of India. The groundwater and the aquifer geochemistry were characterized. The groundwater is characterized by high dissolved Fe, Mn, and HCO-3 and low concentrations of NO-3 and SO2-4 indicating anoxic conditions prevailing in the groundwater. Fifty groundwater samples collected from shallow and deep tubewells of Titabor, Jorhat district (Assam) were examined. Along with total As, examination of concentration levels of other key parameters, viz., pH, EC, Fe, Mn , Mg2+, Ca2+, Na+, K+, PO43- , HCO-3 , NO3- ,Cl - and SO42- was also carried out. In respect to the permissible guideline of World Health Organization (WHO: As 0.01 ppm, Fe 1.0 ppm, and Mn 0.3 ppm for potable water), the range of As concentration in the groundwater varied from 0.014 to 0.604 mg/L with mean concentration 0.184 mg/L. The present study showed that out of the 50 groundwater samples,100%, 54%, and 42% were found contaminated with higher metal contents (for total As, Fe, and Mn, respectively). The results of hydrogeochemical study revealed that the reductive dissolution of MnOOH and FeOOH represents an important mechanism of arsenic release in the study area along with major cations playing an important role in leaching of As into the groundwater. Arsenic released by oxidation of pyrite, as water levels are drawn down and air enters the aquifer, contributes negligibly to the problem of As pollution. Identification of the mechanism of As release to groundwater helps to provide a framework to guide the placement of new water wells so that they will have acceptable concentrations of As.

Keywords: arsenic, assam, brahmaputra floodplain, groundwater, hydrogeochemistry

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Authors: Mahsa Ahmadi, Mehdi Mehdikhani-Nahrkhalaji, Jaleh Varshosaz, Shadi Farsaei

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Gelatin and hyaluronic acid are commonly used in skin tissue engineering scaffolds, but because of their low mechanical properties and high biodegradation rate, adding a synthetic polymer such as polycaprolactone could improve the scaffold properties. Therefore, we developed a gelatin-hyaluronic acid-polycaprolactone scaffold, containing 0.5 % atorvastatin loaded nanostructured lipid carriers (NLCs) for skin tissue engineering. The atorvastatin loaded NLCs solution was prepared by solvent evaporation method and freeze drying process. Synthesized atorvastatin loaded NLCs was added to the gelatin and hyaluronic acid solution, and a membrane was fabricated with solvent evaporation method. Thereafter it was coated by a thin layer of polycaprolactone via spine coating set. The resulting scaffolds were characterized by scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) analyses. Moreover, mechanical properties, in vitro degradation in 7 days period, and in vitro drug release of scaffolds were also evaluated. SEM images showed the uniform distributed NLCs with an average size of 100 nm in the scaffold structure. Mechanical test indicated that the scaffold had a 70.08 Mpa tensile modulus which was twofold of tensile modulus of normal human skin. A Franz-cell diffusion test was performed to investigate the scaffold drug release in phosphate buffered saline (pH=7.4) medium. Results showed that 72% of atorvastatin was released during 5 days. In vitro degradation test demonstrated that the membrane was degradated approximately 97%. In conclusion, suitable physicochemical and biological properties of membrane indicated that the developed gelatin-hyaluronic acid-polycaprolactone nanocomposite scaffold containing 0.5 % atorvastatin loaded NLCs could be used as a good candidate for skin tissue engineering applications.

Keywords: atorvastatin, gelatin, hyaluronic acid, nano lipid carriers (NLCs), polycaprolactone, skin tissue engineering, solvent casting, solvent evaporation

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Authors: S. Pesina, T. Solonchak

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Phenomenological analysis is not based on natural language, but ideal language which is able to be a carrier of ideal meanings – eidos representing typical structures or essences. For this purpose, it’s necessary to release from the spatio-temporal definiteness of a subject and then state its noetic essence (eidos) by means of free fantasy generation. Herewith, as if a totally new objectness is created - the universal, confirming the thesis that thinking process takes place in generalizations passing by numerous means through the specific to the general and from the general through the specific to the singular.

Keywords: lexical eidos, phenomenology, noema, polysemantic word, semantic core

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Authors: Alexsandro Bayestorff da Cunha, Dpebora Caline de Mello, Camila Alves Corrêa

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In the production of fiberboards, an adhesive based on urea-formaldehyde resin is used, which has the advantages of low cost, homogeneity of distribution, solubility in water, high reactivity in an acid medium, and high adhesion to wood. On the other hand, as a disadvantage, there is low resistance to humidity and the release of formaldehyde. The objective of the study was to determine the viability of adding industrial boiler ash to the urea formaldehyde-based adhesive for the production of medium-density fiberboard. The raw material used was composed of Pinus spp fibers, urea-formaldehyde resin, paraffin emulsion, ammonium sulfate, and boiler ash. The experimental plan, consisting of 8 treatments, was completely randomized with a factorial arrangement, with 0%, 1%, 3%, and 5% ash added to the adhesive, with and without the application of a catalyst. In each treatment, 4 panels were produced with density of 750 kg.m⁻³, dimensions of 40 x 40 x 1,5 cm, 12% urea formaldehyde resin, 1% paraffin emulsion and hot pressing at a temperature of 180ºC, the pressure of 40 kgf/cm⁻² for a time of 10 minutes. The different compositions of the adhesive were characterized in terms of viscosity, pH, gel time and solids, and the panels by physical and mechanical properties, in addition to evaluation using the IMAL DPX300 X-ray densitometer and formaldehyde emission by the perforator method. The results showed a significant reduction of all adhesive properties with the use of the catalyst, regardless of the treatment; while the percentage increase of ashes provided an increase in the average values of viscosity, gel time, and solids and a reduction in pH for the panels with a catalyst; for panels without catalyst, the behavior was the opposite, with the exception of solids. For the physical properties, the results of the variables of density, compaction ratio, and thickness were equivalent and in accordance with the standard, while the moisture content was significantly reduced with the use of the catalyst but without the influence of the percentage of ash. The density profile for all treatments was characteristic of medium-density fiberboard, with more compacted and dense surfaces when compared to the central layer. For thickness, the swelling was not influenced by the catalyst and the use of ash, presenting average values within the normalized parameters. For mechanical properties, the influence of ashes on the adhesive was negatively observed in the modulus of rupture from 1% and in the traction test from 3%; however, only this last property, in the percentages of 3% and 5%, were below the minimum limit of the norm. The use of catalyst and ashes with percentages of 3% and 5% reduced the formaldehyde emission of the panels; however, only the panels that used adhesive with catalyst presented emissions below 8mg of formaldehyde / 100g of the panel. In this way, it can be said that boiler ash can be added to the adhesive with a catalyst without impairing the technological properties by up to 1%.

Keywords: reconstituted wood panels, formaldehyde emission, technological properties of panels, perforator

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Authors: Marcin Dębowski, Marcin Zieliński, Mirosław Krzemieniewski

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As methane fermentation is a complex series of successive biochemical transformations, its subsequent stages are determined, to a various extent, by physical and chemical factors. A specific state of equilibrium is being settled in the functioning fermentation system between environmental conditions and the rate of biochemical reactions and products of successive transformations. In the case of physical factors that influence the effectiveness of methane fermentation transformations, the key significance is ascribed to temperature and intensity of biomass agitation. Among the chemical factors, significant are pH value, type, and availability of the culture medium (to put it simply: the C/N ratio) as well as the presence of toxic substances. One of the important elements which influence the effectiveness of methane fermentation is the pre-treatment of organic substrates and the mode in which the organic matter is made available to anaerobes. Out of all known and described methods for organic substrate pre-treatment before methane fermentation process, the ultrasound disintegration is one of the most interesting technologies. Investigations undertaken on the ultrasound field and the use of installations operating on the existing systems result principally from very wide and universal technological possibilities offered by the sonication process. This physical factor may induce deep physicochemical changes in ultrasonicated substrates that are highly beneficial from the viewpoint of methane fermentation processes. In this case, special role is ascribed to disintegration of biomass that is further subjected to methane fermentation. Once cell walls are damaged, cytoplasm and cellular enzymes are released. The released substances – either in dissolved or colloidal form – are immediately available to anaerobic bacteria for biodegradation. To ensure the maximal release of organic matter from dead biomass cells, disintegration processes are aimed to achieve particle size below 50 μm. It has been demonstrated in many research works and in systems operating in the technical scale that immediately after substrate supersonication the content of organic matter (characterized by COD, BOD5 and TOC indices) was increasing in the dissolved phase of sedimentation water. This phenomenon points to the immediate sonolysis of solid substances contained in the biomass and to the release of cell material, and consequently to the intensification of the hydrolytic phase of fermentation. It results in a significant reduction of fermentation time and increased effectiveness of production of gaseous metabolites of anaerobic bacteria. Because disintegration of Virginia fanpetals biomass via ultrasounds applied in order to intensify its conversion is a novel technique, it is often underestimated by exploiters of agri-biogas works. It has, however, many advantages that have a direct impact on its technological and economical superiority over thus far applied methods of biomass conversion. As for now, ultrasound disintegrators for biomass conversion are not produced on the mass-scale, but by specialized groups in scientific or R&D centers. Therefore, their quality and effectiveness are to a large extent determined by their manufacturers’ knowledge and skills in the fields of acoustics and electronic engineering.

Keywords: ultrasound disintegration, biomass, methane fermentation, biogas, Virginia fanpetals

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