Search results for: gaseous agent
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1687

Search results for: gaseous agent

1267 The Effect of Filter Cake Powder on Soil Stability Enhancement in Active Sand Dunes, In the Long and Short Term

Authors: Irit Rutman Halili, Tehila Zvulun, Natali Elgabsi, Revaya Cohen, Shlomo Sarig

Abstract:

Active sand dunes (ASD) may cause significant damage to field crops and livelihood, and therefore, it is necessary to find a treatment that would enhance ADS soil stability. Biological soil crusts (biocrusts) contain microorganisms on the soil surface. Metabolic polysaccharides secreted by biocrust cyanobacteria glue the soil particles into aggregates, thereby stabilizing the soil surface. Filter cake powder (FCP) is a waste by-product in the final stages of the production of sugar from sugarcane, and its disposal causes significant environmental pollution. FCP contains high concentrations of polysaccharides and has recently been shown to be soil stability enhancing agent in ASD. It has been reported that adding FCP to the ASD soil surface by dispersal significantly increases the level of penetration resistance of soil biocrust (PRSB) nine weeks after a single treatment. However, it was not known whether a similar effect could be obtained by administering the FCP in liquid form by means of spraying. It has now been found that spraying a water solution of FCP onto the ASD soil surface significantly increased the level of penetration resistance of soil biocrust (PRSB) three weeks after a single treatment. These results suggest that FCP spraying can be used as a short-term soil stability-enhancing agent for ASD, while administration by dispersal might be more efficient over the long term. Finally, an additional benefit of using FCP as a soil stabilizer, either by dispersal or by spraying, is the reduction in environmental pollution that would otherwise result from the disposal of FCP solid waste.

Keywords: active sand dunes, filter cake powder, biological soil crusts, penetration resistance of soil biocrust

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1266 Topochemical Synthesis of Epitaxial Silicon Carbide on Silicon

Authors: Andrey V. Osipov, Sergey A. Kukushkin, Andrey V. Luk’yanov

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A method is developed for the solid-phase synthesis of epitaxial layers when the substrate itself is involved into a topochemical reaction and the reaction product grows in the interior of substrate layer. It opens up new possibilities for the relaxation of the elastic energy due to the attraction of point defects formed during the topochemical reaction in anisotropic media. The presented method of silicon carbide (SiC) formation employs a topochemical reaction between the single-crystalline silicon (Si) substrate and gaseous carbon monoxide (CO). The corresponding theory of interaction of point dilatation centers in anisotropic crystals is developed. It is eliminated that the most advantageous location of the point defects is the direction (111) in crystals with cubic symmetry. The single-crystal SiC films with the thickness up to 200 nm have been grown on Si (111) substrates owing to the topochemical reaction with CO. Grown high-quality single-crystal SiC films do not contain misfit dislocations despite the huge lattice mismatch value of ~20%. Also the possibility of growing of thick wide-gap semiconductor films on these templates SiC/Si(111) and, accordingly, its integration into Si electronics, is demonstrated. Finally, the ab initio theory of SiC formation due to the topochemical reaction has been developed.

Keywords: epitaxy, silicon carbide, topochemical reaction, wide-bandgap semiconductors

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1265 Applications of Evolutionary Optimization Methods in Reinforcement Learning

Authors: Rahul Paul, Kedar Nath Das

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The paradigm of Reinforcement Learning (RL) has become prominent in training intelligent agents to make decisions in environments that are both dynamic and uncertain. The primary objective of RL is to optimize the policy of an agent in order to maximize the cumulative reward it receives throughout a given period. Nevertheless, the process of optimization presents notable difficulties as a result of the inherent trade-off between exploration and exploitation, the presence of extensive state-action spaces, and the intricate nature of the dynamics involved. Evolutionary Optimization Methods (EOMs) have garnered considerable attention as a supplementary approach to tackle these challenges, providing distinct capabilities for optimizing RL policies and value functions. The ongoing advancement of research in both RL and EOMs presents an opportunity for significant advancements in autonomous decision-making systems. The convergence of these two fields has the potential to have a transformative impact on various domains of artificial intelligence (AI) applications. This article highlights the considerable influence of EOMs in enhancing the capabilities of RL. Taking advantage of evolutionary principles enables RL algorithms to effectively traverse extensive action spaces and discover optimal solutions within intricate environments. Moreover, this paper emphasizes the practical implementations of EOMs in the field of RL, specifically in areas such as robotic control, autonomous systems, inventory problems, and multi-agent scenarios. The article highlights the utilization of EOMs in facilitating RL agents to effectively adapt, evolve, and uncover proficient strategies for complex tasks that may pose challenges for conventional RL approaches.

Keywords: machine learning, reinforcement learning, loss function, optimization techniques, evolutionary optimization methods

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1264 Molecular Epidemiology of Circulating Adenovirus Types in Acute Conjunctivitis Cases in Chandigarh, North India

Authors: Mini P. Singh, Jagat Ram, Archit Kumar, Tripti Rungta, Jasmine Khurana, Amit Gupta, R. K. Ratho

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Introduction: Human adenovirus is the most common agent involved in viral conjunctivitis. The clinical manifestations vary with different serotypes. The identification of the circulating strains followed by phylogenetic analysis can be helpful in understanding the origin and transmission of the disease. The present study aimed to carry out molecular epidemiology of the adenovirus types in the patients with conjunctivitis presenting to the eye centre of a tertiary care hospital in North India. Materials and Methods: The conjunctival swabs were collected from 23 suspected adenoviral conjunctivitis patients between April-August, 2014 and transported in viral transport media. The samples were subjected to nested PCR targeting hexon gene of human adenovirus. The band size of 956bp was eluted and 8 representative positive samples were subjected to sequencing. The sequences were analyzed by using CLUSTALX2.1 and MEGA 5.1 software. Results: The male: female ratio was found to be 3.6:1. The mean age of presenting patients was 43.95 years (+17.2). Approximately 52.1% (12/23) of patients presented with bilateral involvement while 47.8% (11/23) with unilateral involvement of the eye. Human adenovirus DNA could be detected in 65.2% (15/23) of the patients. The phylogenetic analysis revealed presence of serotype 8 in 7 patients and serotype 4 in one patient. The serotype 8 sequences showed 99-100% identity with Tunisian, Indian and Japanese strains. The adenovirus serotype 4 strains had 100% identity with strains from Tunisia, China and USA. Conclusion: Human adenovirus was found be an important etiological agent for conjunctivitis in our set up. The phylogenetic analysis showed that the predominant circulating strains in our epidemic keratoconjunctivitis were serotypes 8 and 4.

Keywords: conjunctivitis, human adenovirus, molecular epidemiology, phylogenetics

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1263 Bionaut™: A Microrobotic Drug-Device Platform for the Local Treatment of Brainstem Gliomas

Authors: Alex Kiselyov, Suehyun Cho, Darrell Harrington; Florent Cros, Olin Palmer, John Caputo, Michael Kardosh, Eran Oren, William Loudon, Michael Shpigelmacher

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Despite the most aggressive surgical and adjuvant therapeutic strategies, treatment of both pediatric and adult brainstem tumors remains problematic. Novel strategies, including targeted biologics, immunotherapy, and specialized delivery systems such as convection-enhanced delivery (CED), have been proposed. While some of these novel treatments are entering phase I trials, the field is still in need of treatment(s) that exhibits dramatically enhanced potency with optimal therapeutic ratio. Bionaut Labs has developed a modular microrobotic platform for performing localized delivery of diverse therapeutics in vivo. Our biocompatible particles (Bionauts™) are externally propelled and visualized in real-time. Bionauts™ are specifically designed to enhance the effect of radiation therapy via anatomically precise delivery of a radiosensitizing agent, as exemplified by temozolomide (TMZ) and Avastin™ to the brainstem gliomas of diverse origin. The treatment protocol is designed to furnish a better therapeutic outcome due to the localized (vs systemic) delivery of the drug to the neoplastic lesion(s) for use as a synergistic combination of radiation and radiosensitizing agent. In addition, the procedure is minimally invasive and is expected to be appropriate for both adult and pediatric patients. Current progress, including platform optimization, selection of the lead radiosensitizer as well as in vivo safety studies of the Bionauts™ in large animals, specifically the spine and the brain of porcine and ovine models, will be discussed.

Keywords: Bionaut, brainstem, glioma, local delivery, micro-robot, radiosensitizer

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1262 Cement Bond Characteristics of Artificially Fabricated Sandstones

Authors: Ashirgul Kozhagulova, Ainash Shabdirova, Galym Tokazhanov, Minh Nguyen

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The synthetic rocks have been advantageous over the natural rocks in terms of availability and the consistent studying the impact of a particular parameter. The artificial rocks can be fabricated using variety of techniques such as mixing sand and Portland cement or gypsum, firing the mixture of sand and fine powder of borosilicate glass or by in-situ precipitation of calcite solution. In this study, sodium silicate solution has been used as the cementing agent for the quartz sand. The molded soft cylindrical sandstone samples are placed in the gas-tight pressure vessel, where the hardening of the material takes place as the chemical reaction between carbon dioxide and the silicate solution progresses. The vessel allows uniform disperse of carbon dioxide and control over the ambient gas pressure. Current paper shows how the bonding material is initially distributed in the intergranular space and the surface of the sand particles by the usage of Electron Microscopy and the Energy Dispersive Spectroscopy. During the study, the strength of the cement bond as a function of temperature is observed. The impact of cementing agent dosage on the micro and macro characteristics of the sandstone is investigated. The analysis of the cement bond at micro level helps to trace the changes to particles bonding damage after a potential yielding. Shearing behavior and compressional response have been examined resulting in the estimation of the shearing resistance and cohesion force of the sandstone. These are considered to be main input values to the mathematical prediction models of sand production from weak clastic oil reservoir formations.

Keywords: artificial sanstone, cement bond, microstructure, SEM, triaxial shearing

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1261 Spectrum and Prevalence of Candida Infection in Diabetic Foot Ulcers

Authors: Seyed Reza Aghili, Tahereh Shokohi, Lotfollah Davoodi, Zahra Kashi, Azam Moslemi, Mahdi Abastabar, Iman Haghani, Sabah Mayahi, Asoudeh A.

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Introduction: In diabetic foot ulcers, if fungal agents such as Candida species penetrate into the cutaneous or depth of ulcer, can increase the degree of the wound and cause Candia infection and make it more difficult to heal. Material & Methods: A cross-sectional study was performed on 100 diabetic foot ulcer patients in 2020 in Sari, Iran. patient's data and wound grade were recorded in a questionnaire. Candida infection was diagnosed with direct microscopic examination and culture of samples. Colony-PCR molecular method was used for ITS region of DNA and then PCR-RFLP with Msp1 enzyme and using HWP1 specific gene to determine species of Candida agent. Results: Of 100 patients, the mean age 62.1 ± 10.8 years, 95% type 2 diabetes, 83%>10 years duration diabetes, 59% male, 66%> poor education level, 99% married, 52% rural, 95% neuropathic symptoms, 88% using antibiotics, 69%HbA1C >9%, and mean ulcer degree 2.6±1.05 were. Candida infection was seen in 13% of the deep tissue of the wound and 7% cutaneous around the wound. The predominant Candida isolated was C. parapsilosis (71.5%), C .albicans (14.3%). Fungal infections caused by mold fungi were not detected. There was a statistically significant relationship between yeast infection and gender, rural, HbA1C and ulcer degree. Conclusion: Mycological evaluations often are ignored. Candida parapsilosis is the most common infectious agent in these patients and may require specific treatment. Therefore, more attention of physicians to Candida infections particularly, early diagnosis and effective treatment can help faster recovery and prevent amputation.

Keywords: diabetic foot ulcer, candida infection, risk factors, c. parapsilosis

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1260 Widely Diversified Macroeconomies in the Super-Long Run Casts a Doubt on Path-Independent Equilibrium Growth Model

Authors: Ichiro Takahashi

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One of the major assumptions of mainstream macroeconomics is the path independence of capital stock. This paper challenges this assumption by employing an agent-based approach. The simulation results showed the existence of multiple "quasi-steady state" equilibria of the capital stock, which may cast serious doubt on the validity of the assumption. The finding would give a better understanding of many phenomena that involve hysteresis, including the causes of poverty. The "market-clearing view" has been widely shared among major schools of macroeconomics. They understand that the capital stock, the labor force, and technology, determine the "full-employment" equilibrium growth path and demand/supply shocks can move the economy away from the path only temporarily: the dichotomy between the short-run business cycles and the long-run equilibrium path. The view then implicitly assumes the long-run capital stock to be independent of how the economy has evolved. In contrast, "Old Keynesians" have recognized fluctuations in output as arising largely from fluctuations in real aggregate demand. It will then be an interesting question to ask if an agent-based macroeconomic model, which is known to have path dependence, can generate multiple full-employment equilibrium trajectories of the capital stock in the super-long run. If the answer is yes, the equilibrium level of capital stock, an important supply-side factor, would no longer be independent of the business cycle phenomenon. This paper attempts to answer the above question by using the agent-based macroeconomic model developed by Takahashi and Okada (2010). The model would serve this purpose well because it has neither population growth nor technology progress. The objective of the paper is twofold: (1) to explore the causes of long-term business cycle, and (2) to examine the super-long behaviors of the capital stock of full-employment economies. (1) The simulated behaviors of the key macroeconomic variables such as output, employment, real wages showed widely diversified macro-economies. They were often remarkably stable but exhibited both short-term and long-term fluctuations. The long-term fluctuations occur through the following two adjustments: the quantity and relative cost adjustments of capital stock. The first one is obvious and assumed by many business cycle theorists. The reduced aggregate demand lowers prices, which raises real wages, thereby decreasing the relative cost of capital stock with respect to labor. (2) The long-term business cycles/fluctuations were synthesized with the hysteresis of real wages, interest rates, and investments. In particular, a sequence of the simulation runs with a super-long simulation period generated a wide range of perfectly stable paths, many of which achieved full employment: all the macroeconomic trajectories, including capital stock, output, and employment, were perfectly horizontal over 100,000 periods. Moreover, the full-employment level of capital stock was influenced by the history of unemployment, which was itself path-dependent. Thus, an experience of severe unemployment in the past kept the real wage low, which discouraged a relatively costly investment in capital stock. Meanwhile, a history of good performance sometimes brought about a low capital stock due to a high-interest rate that was consistent with a strong investment.

Keywords: agent-based macroeconomic model, business cycle, hysteresis, stability

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1259 Current Status of Scaled-Up Synthesis/Purification and Characterization of a Potentially Translatable Tantalum Oxide Nanoparticle Intravenous CT Contrast Agent

Authors: John T. Leman, James Gibson, Peter J. Bonitatibus

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There have been no potential clinically translatable developments of intravenous CT contrast materials over decades, and iodinated contrast agents (ICA) remain the only FDA-approved media for CT. Small molecule ICA used to highlight vascular anatomy have weak CT signals in large-to-obese patients due to their rapid redistribution from plasma into interstitial fluid, thereby diluting their intravascular concentration, and because of a mismatch of iodine’s K-edge and the high kVp settings needed to image this patient population. The use of ICA is also contraindicated in a growing population of renally impaired patients who are hypersensitive to these contrast agents; a transformative intravenous contrast agent with improved capabilities is urgently needed. Tantalum oxide nanoparticles (TaO NPs) with zwitterionic siloxane polymer coatings have high potential as clinically translatable general-purpose CT contrast agents because of (1) substantially improved imaging efficacy compared to ICA in swine/phantoms emulating medium-sized and larger adult abdomens and superior thoracic vascular contrast enhancement of thoracic arteries and veins in rabbit, (2) promising biological safety profiles showing near-complete renal clearance and low tissue retention at 3x anticipated clinical dose (ACD), and (3) clinically acceptable physiochemical parameters as concentrated bulk solutions(250-300 mgTa/mL). Here, we review requirements for general-purpose intravenous CT contrast agents in terms of patient safety, X-ray attenuating properties and contrast-producing capabilities, and physicochemical and pharmacokinetic properties. We report the current status of a TaO NP-based contrast agent, including chemical process technology developments and results of newly defined scaled-up processes for NP synthesis and purification, yielding reproducible formulations with appropriate size and concentration specifications. We discuss recent results of recent pre-clinical in vitro immunology, non-GLP high dose tolerability in rats (10x ACD), non-GLP long-term biodistribution in rats at 3x ACD, and non-GLP repeat dose in rats at ACD. We also include a discussion of NP characterization, in particular size-stability testing results under accelerated conditions (37C), and insights into TaO NP purity, surface structure, and bonding of the zwitterionic siloxane polymer coating by multinuclear (1H, 13C, 29Si) and multidimensional (2D) solution NMR spectroscopy.

Keywords: nanoparticle, imaging, diagnostic, process technology, nanoparticle characterization

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1258 Micro-Cantilever Tests on Hydride Blister and Zirconium Matrix of Zircaloy-4 Cladding Tube

Authors: Ho-A Kim, Jae-Soo Noh

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During reactor operation, hydride blister can occur in spent nuclear fuel (SNF) claddings, and it could worsen the integrity of the claddings locally. Hydride blister can be critical when a pinch-type load is applied in the process of SNF handling and transportation. Micro-cantilever tests were performed to evaluate the risk of local hydride blister by comparing the fracture toughness of local hydride blister and pre-hydrided Zr alloy matrix of SNF cladding on a microscale. Hydride blister was generated by a gaseous charging procedure to simulate an SNF cladding. Micro-cantilevers and pre-cracks were ion-milled with the Ga+ ion beam of FEI Helios 600 at 30kV acceleration voltage. Micro-cantilever tests were conducted using PI 85 pico-indenter (HYSTRON) with for sided conductive diamond flat tip (1 μm x 1 μm) at a speed of 5 nm/sec. The results show that the hydride blister specimen could be fractured in the elastic deformation region, and the fracture toughness of the hydride blister specimen could drop up to 60% of that of the pre-hydrided Zr alloy matrix. Therefore, local hydride blister can degrade the integrity of SNF cladding, and the effect of hydride blister should be taken into account when evaluating failure criteria of claddings during handling, storage, and transportation of SNF.

Keywords: fracture toughness, hydride blister, micro-cantilever test, spent nuclear fuel cladding.

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1257 Evaluating the Prominence of Chemical Phenomena in Chemistry Courses

Authors: Vanessa R. Ralph, Leah J. Scharlott, Megan Y. Deshaye, Ryan L. Stowe

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Given the traditions of chemistry teaching, one may not question whether chemical phenomena play a prominent role. Yet, the role of chemical phenomena in an introductory chemistry course may define the extent to which the course is introductory, chemistry, and equitable. Picture, for example, the classic Ideal Gas Law problem. If one envisions a prompt wherein students are tasked with calculating a missing variable, then one envisions a prompt that relies on chemical phenomena as a context rather than as a model to understand the natural world. Consider a prompt wherein students are tasked with applying molecular models of gases to explain why the vapor pressure of a gaseous solution of water differs from that of carbon dioxide. Here, the chemical phenomenon is not only the context but also the subject of the prompt. Deliveries of general and organic chemistry were identified as ranging wildly in the integration of chemical phenomena. The more incorporated the phenomena, the more equitable the assessment task was for students of varying access to pre-college math and science preparation. How chemical phenomena are integrated may very well define whether courses are chemistry, are introductory, and are equitable. Educators of chemistry are invited colleagues to discuss the role of chemical phenomena in their courses and consider the long-lasting impacts of replicating tradition for tradition’s sake.

Keywords: equitable educational practices, chemistry curriculum, content organization, assessment design

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1256 Seaweed as a Future Fuel Option: Potential and Conversion Technologies

Authors: Muhammad Rizwan Tabassum, Ao Xia, Jerry D. Murphy

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The purpose of this work is to provide a comprehensive overview of seaweed as the alternative feedstock for biofuel production and key conversion technologies. Resource depletion and climate change are the driving forces to hunt for renewable sources of energy. Macroalgae can be preferred over land based crops for biofuel production because they are not in competition with food crops for arable land, high growth rates and low lignin contents which require less energy-intensive pre-treatments. However, some disadvantages, such as high moisture content, seasonal variation in chemical composition and process inhibition limit its economic feasibility. Seaweed can be converted into gaseous and liquid fuel by different conversion technologies, but biogas via anaerobic digestion from seaweed is attracting increased attention due to its dual benefit of an economic source of bio-fuel and environment-friendly technology. Biodiesel and bioethanol conversion technologies from seaweed are still under development. A selection of high yielding seaweed species, optimal harvesting season and process optimization make them economically feasible for the alternative source of renewable and sustainable feedstock for biofuel in future.

Keywords: anaerobic digestion, biofuel, bio-methane, conversion technologies, seaweed

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1255 Time Series Analysis of Air Pollution in Suceava County ( Nord- East of Romania)

Authors: Lazurca Liliana Gina

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Different time series analysis of yearly air pollution at Suceava County, Nord-East of Romania, has been performed in this study. The trends in the atmospheric concentrations of the main gaseous and particulate pollutants in urban, industrial and rural environments across Suceava County were estimated for the period of 2008-2014. The non-parametric Mann-Kendall test was used to determine the trends in the annual average concentrations of air pollutants (NO2, NO, NOx, SO2, CO, PM10, O3, C6H6). The slope was estimated using the non-parametric Sen’s method. Trend significance was assumed at the 5% significance level (p < 0.05) in the current study. During the 7 year period, trends in atmospheric concentrations may not have been monotonic, in some instances concentrations of species increased and subsequently decreased. The trend in Suceava County is to keep a low concentration of pollutants in ambient air respecting the limit values.All the results that we obtained show that Romania has taken a lot of regulatory measures to decrease the concentrations of air pollutants in the last decade, in Suceava County the air quality monitoring highlight for the most part of the analyzed pollutants decreasing trends. For the analyzed period we observed considerable improvements in background air in Suceava County.

Keywords: pollutant, trend, air quality monitoring, Mann-Kendall

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1254 The Effect of Pregabalin on Postoperative Pain after Anterior Cruciate Ligament Reconstruction: A Systematic Review of Randomized Clinical Trials

Authors: Emad Kouhestani

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Background: Despite the enormous success of anterior cruciate ligament (ACL) reconstruction, acute neuropathic pain can develop postoperatively and is both distressing and difficult to treat once established. Pregabalin, as an anticonvulsant agent that selectively affects the nociceptive process, has been used as a pain relief agent. The purpose of this systematic review of randomized controlled trials (RCTs) was to evaluate the pain control effect of pregabalin versus placebo after ACL reconstruction. Method: A search of the literature was performed from inception to June 2022, using PubMed, Scopus, Google Scholar, Web of Science, Cochrane, and EBSCO. Studies considered for inclusion were RCTs that reported relevant outcomes (postoperative pain scores, or cumulative opioid consumption, adverse events) following the administration of pregabalin in patients undergoing ACL reconstruction. Result: Five placebo-controlled RCTs involving 272 participants met the inclusion criteria. 75 mg and 150 mg of oral pregabalin were used in included trials. Two studies used a single dose of pregabalin one hour before anesthesia induction. Two studies used pregabalin 1 hour before anesthesia induction and 12 hours after. One study used daily pregabalin 7 days before and 7 days after surgery. Out of five papers, three papers found significantly lower pain intensity and cumulative opioid consumption in the pregabalin group compared with the placebo group. However, a decrease in pain scores was found in all trials. Pregabalin administration was associated with dizziness and nausea. Conclusion: The use of pregabalin may be a valuable asset in pain management after ACL reconstruction. However, future studies with larger sample sizes and longer follow-up periods are required.

Keywords: pregabalin, anterior cruciate ligament, postoperative pain, clinical trial

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1253 Therapeutic Challenges in Treatment of Adults Bacterial Meningitis Cases

Authors: Sadie Namani, Lindita Ajazaj, Arjeta Zogaj, Vera Berisha, Bahrije Halili, Luljeta Hasani, Ajete Aliu

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Background: The outcome of bacterial meningitis is strongly related to the resistance of bacterial pathogens to the initial antimicrobial therapy. The objective of the study was to analyze the initial antimicrobial therapy, the resistance of meningeal pathogens and the outcome of adults bacterial meningitis cases. Materials/methods: This prospective study enrolled 46 adults older than 16 years of age, treated for bacterial meningitis during the years 2009 and 2010 at the infectious diseases clinic in Prishtinë. Patients are categorized into specific age groups: > 16-26 years of age (10 patients), > 26-60 years of age (25 patients) and > 60 years of age (11 patients). All p-values < 0.05 were considered statistically significant. Data were analyzed using Stata 7.1 and SPSS 13. Results: During the two year study period 46 patients (28 males) were treated for bacterial meningitis. 33 patients (72%) had a confirmed bacterial etiology; 13 meningococci, 11 pneumococci, 7 gram-negative bacilli (Ps. aeruginosa 2, Proteus sp. 2, Acinetobacter sp. 2 and Klebsiella sp. 1 case) and 2 staphylococci isolates were found. Neurological complications developed in 17 patients (37%) and the overall mortality rate was 13% (6 deaths). Neurological complications observed were: cerebral abscess (7/46; 15.2%), cerebral edema (4/46; 8.7%); haemiparesis (3/46; 6.5%); recurrent seizures (2/46; 4.3%), and single cases of thrombosis sinus cavernosus, facial nerve palsy and decerebration (1/46; 2.1%). The most common meningeal pathogens were meningococcus in the youngest age group, gram negative-bacilli in second age group and pneumococcus in eldery age group. Initial single-agent antibiotic therapy (ceftriaxone) was used in 17 patients (37%): in 60% of patients in the youngest age group and in 44% of cases in the second age group. 29 patients (63%) were treated with initial dual-agent antibiotic therapy; ceftriaxone in combination with vancomycin or ampicillin. Ceftriaxone and ampicillin were the most commonly used antibiotics for the initial empirical therapy in adults > 50 years of age. All adults > 60 years of age were treated with the initial dual-agent antibiotic therapy as in this age group was recorded the highest mortality rate (M=27%) and adverse outcome (64%). Resistance of pathogens to antimicrobics was recorded in cases caused by gram-negative bacilli and was associated with greater risk for developing neurological complications (p=0.09). None of the gram-negative bacilli were resistant to carbapenems; all were resistant to ampicillin while 5/7 isolates were resistant to cefalosporins. Resistance of meningococci and pneumococci to beta-lactams was not recorded. There were no statistical differences in the occurrence of neurological complications (p > 0.05), resistance of meningeal pathogens to antimicrobics (p > 0.05) and the inital antimicrobial therapy (one vs. two antibiotics) concerning group-ages in adults. Conclusions: The initial antibiotic therapy with ceftriaxone alone or in combination with vancomycin or ampicillin did not cover cases caused by gram-negative bacilli.

Keywords: adults, bacterial meningitis, outcomes, therapy

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1252 Fluidized-Bed Combustion of Biomass with Elevated Alkali Content: A Comparative Study between Two Alternative Bed Materials

Authors: P. Ninduangdee, V. I. Kuprianov

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Palm kernel shell is an important bioenergy resource in Thailand. However, due to elevated alkali content in biomass ash, this oil palm residue shows high tendency to bed agglomeration in a fluidized-bed combustion system using conventional bed material (silica sand). In this study, palm kernel shell was burned in the conical fluidized-bed combustor (FBC) using alumina and dolomite as alternative bed materials to prevent bed agglomeration. For each bed material, the combustion tests were performed at 45kg/h fuel feed rate with excess air within 20–80%. Experimental results revealed rather weak effects of the bed material type but substantial influence of excess air on the behaviour of temperature, O2, CO, CxHy, and NO inside the reactor, as well as on the combustion efficiency and major gaseous emissions of the conical FBC. The optimal level of excess air ensuring high combustion efficiency (about 98.5%) and acceptable level of the emissions was found to be about 40% when using alumina and 60% with dolomite. By using these alternative bed materials, bed agglomeration can be prevented when burning the shell in the proposed conical FBC. However, both bed materials exhibited significant changes in their morphological, physical and chemical properties in the course of the time.

Keywords: palm kernel shell, fluidized-bed combustion, alternative bed materials, combustion and emission performance, bed agglomeration prevention

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1251 The Optimization of Topical Antineoplastic Therapy Using Controlled Release Systems Based on Amino-functionalized Mesoporous Silica

Authors: Lacramioara Ochiuz, Aurelia Vasile, Iulian Stoleriu, Cristina Ghiciuc, Maria Ignat

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Topical administration of chemotherapeutic agents (eg. carmustine, bexarotene, mechlorethamine etc.) in local treatment of cutaneous T-cell lymphoma (CTCL) is accompanied by multiple side effects, such as contact hypersensitivity, pruritus, skin atrophy or even secondary malignancies. A known method of reducing the side effects of anticancer agent is the development of modified drug release systems using drug incapsulation in biocompatible nanoporous inorganic matrices, such as mesoporous MCM-41 silica. Mesoporous MCM-41 silica is characterized by large specific surface, high pore volume, uniform porosity, and stable dispersion in aqueous medium, excellent biocompatibility, in vivo biodegradability and capacity to be functionalized with different organic groups. Therefore, MCM-41 is an attractive candidate for a wide range of biomedical applications, such as controlled drug release, bone regeneration, protein immobilization, enzymes, etc. The main advantage of this material lies in its ability to host a large amount of the active substance in uniform pore system with adjustable size in a mesoscopic range. Silanol groups allow surface controlled functionalization leading to control of drug loading and release. This study shows (I) the amino-grafting optimization of mesoporous MCM-41 silica matrix by means of co-condensation during synthesis and post-synthesis using APTES (3-aminopropyltriethoxysilane); (ii) loading the therapeutic agent (carmustine) obtaining a modified drug release systems; (iii) determining the profile of in vitro carmustine release from these systems; (iv) assessment of carmustine release kinetics by fitting on four mathematical models. Obtained powders have been described in terms of structure, texture, morphology thermogravimetric analysis. The concentration of the therapeutic agent in the dissolution medium has been determined by HPLC method. In vitro dissolution tests have been done using cell Enhancer in a 12 hours interval. Analysis of carmustine release kinetics from mesoporous systems was made by fitting to zero-order model, first-order model Higuchi model and Korsmeyer-Peppas model, respectively. Results showed that both types of highly ordered mesoporous silica (amino grafted by co-condensation process or post-synthesis) are thermally stable in aqueous medium. In what regards the degree of loading and efficiency of loading with the therapeutic agent, there has been noticed an increase of around 10% in case of co-condensation method application. This result shows that direct co-condensation leads to even distribution of amino groups on the pore walls while in case of post-synthesis grafting many amino groups are concentrated near the pore opening and/or on external surface. In vitro dissolution tests showed an extended carmustine release (more than 86% m/m) both from systems based on silica functionalized directly by co-condensation and after synthesis. Assessment of carmustine release kinetics revealed a release through diffusion from all studied systems as a result of fitting to Higuchi model. The results of this study proved that amino-functionalized mesoporous silica may be used as a matrix for optimizing the anti-cancer topical therapy by loading carmustine and developing prolonged-release systems.

Keywords: carmustine, silica, controlled, release

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1250 Recycling of Polymers in the Presence of Nanocatalysts: A Green Approach towards Sustainable Environment

Authors: Beena Sethi

Abstract:

This work involves the degradation of plastic waste in the presence of three different nanocatalysts. A thin film of LLDPE was formed with all three nanocatalysts separately in the solvent. Thermo Gravimetric Analysis (TGA) and Differential Scanning Calorimetric (DSC) analysis of polymers suggest that the presence of these catalysts lowers the degradation temperature and the change mechanism of degradation. Gas chromatographic analysis was carried out for two films. In gas chromatography (GC) analysis, it was found that degradation of pure polymer produces only 32% C3/C4 hydrocarbons and 67.6% C5/C9 hydrocarbons. In the presence of these catalysts, more than 80% of polymer by weight was converted into either liquid or gaseous hydrocarbons. Change in the mechanism of degradation of polymer was observed therefore more C3/C4 hydrocarbons along with valuable feedstock are produced. Adjustment of dose of nanocatalyst, use of nano-admixtures and recycling of catalyst can make this catalytic feedstock recycling method a good tool to get sustainable environment. The obtained products can be utilized as fuel or can be transformed into other useful products. In accordance with the principles of sustainable development, chemical recycling i.e. tertiary recycling of polymers along with the reuse (zero order recycling) of plastics can be the most appropriate and promising method in this direction. The tertiary recycling is attracting much attention from the viewpoint of the energy resource.

Keywords: degradation, differential scanning calorimetry, feedstock recycling, gas chromatography, thermogravimetric analysis

Procedia PDF Downloads 411
1249 Effect of Modification and Expansion on Emergence of Cooperation in Demographic Multi-Level Donor-Recipient Game

Authors: Tsuneyuki Namekata, Yoko Namekata

Abstract:

It is known that the mean investment evolves from a very low initial value to some high level in the Continuous Prisoner's Dilemma. We examine how the cooperation level evolves from a low initial level to a high level in our Demographic Multi-level Donor-Recipient situation. In the Multi-level Donor-Recipient game, one player is selected as a Donor and the other as a Recipient randomly. The Donor has multiple cooperative moves and one defective move. A cooperative move means the Donor pays some cost for the Recipient to receive some benefit. The more cooperative move the Donor takes, the higher cost the Donor pays and the higher benefit the Recipient receives. The defective move has no effect on them. Two consecutive Multi-level Donor-Recipient games, one as a Donor and the other as a Recipient, can be viewed as a discrete version of the Continuous Prisoner's Dilemma. In the Demographic Multi-level Donor-Recipient game, players are initially distributed spatially. In each period, players play multiple Multi-level Donor-Recipient games against other players. He leaves offspring if possible and dies because of negative accumulated payoff of him or his lifespan. Cooperative moves are necessary for the survival of the whole population. There is only a low level of cooperative move besides the defective move initially available in strategies of players. A player may modify and expand his strategy by his recent experiences or practices. We distinguish several types of a player about modification and expansion. We show, by Agent-Based Simulation, that introducing only the modification increases the emergence rate of cooperation and introducing both the modification and the expansion further increases it and a high level of cooperation does emerge in our Demographic Multi-level Donor-Recipient Game.

Keywords: agent-based simulation, donor-recipient game, emergence of cooperation, spatial structure, TFT, TF2T

Procedia PDF Downloads 356
1248 Experimental Investigation of Hybrid Rocket Motor: Ignition, Throttling and Re-Ignition Phenomena

Authors: A. El-S. Makled, M. K. Al-Tamimi

Abstract:

Ignition phenomena are of great interest area over the past many years, and it has a direct impact on many propulsion and combustion applications. The direct goal of the paper is to realize and evaluate a functioning ignition method, shut-off, throttling and re-start operations for the hybrid rocket motor. A small-scale hybrid rocket motor (SSHRM) is designed, manufactured, demonstrated at various operating conditions and finally equipped for laboratory firing tests with high level of safety. Various solid fuel grains as Polymethyle-methacrylate (PMMA) and Polyethylene (PE) are selected, and it is decided to use the commercial gaseous oxygen (GO2) for its availability and low cost. Examine different types of ignition methods, pyrotechnic charge, fuse wire, heat wire and finally hot oxidizer method by using the heat exchanger, which are proposed as very safe ignition methods. Finally; recognize phenomena of throttling and re-start operations. Ignition by hot GO2 impingement is proved to be a very attractive ignition method for laboratory SSHRM, for its high safety, reliability and acceptable delay time. Finally; the throttling and re-start operations are demonstrated several times and can be carried out more easily with hot air ignition method.

Keywords: hybrid rocket motor, ignition system, re-start phenomena, throttling

Procedia PDF Downloads 293
1247 Real Time Monitoring and Control of Proton Exchange Membrane Fuel Cell in Cognitive Radio Environment

Authors: Prakash Thapa, Gye Choon Park, Sung Gi Kwon, Jin Lee

Abstract:

The generation of electric power from a proton exchange membrane (PEM) fuel cell is influenced by temperature, pressure, humidity, flow rate of reactant gaseous and partial flooding of membrane electrode assembly (MEA). Among these factors, temperature and cathode flooding are the most affecting parameters on the performance of fuel cell. This paper describes the detail design and effect of these parameters on PEM fuel cell. Performance of all parameters was monitored, analyzed and controlled by using 5KWatt PEM fuel cell. In the real-time data communication for remote monitoring and control of PEM fuel cell, a normalized least mean square algorithm in cognitive radio environment is used. By the use of this method, probability of energy signal detection will be maximum which solved the frequency shortage problem. So the monitoring system hanging out and slow speed problem will be solved. Also from the control unit, all parameters are controlled as per the system requirement. As a result, PEM fuel cell generates maximum electricity with better performance.

Keywords: proton exchange membrane (PEM) fuel cell, pressure, temperature and humidity sensor (PTH), efficiency curve, cognitive radio network (CRN)

Procedia PDF Downloads 447
1246 The Effect of the Combination of Methotrexate Nanoparticles and TiO2 on Breast Cancer

Authors: Nusaiba Al-Nemrawi, Belal Al-Husein

Abstract:

Methotrexate (MTX) is a stoichiometric inhibitor of dihydrofolate reductase, which is essential for DNA synthesis. MTX is a chemotherapeutic agent used for treating many types of cancer cells. However, cells’ resistant to MTX is very common and its pharmacokinetic behavior is highly problematic. of MTX within tumor cells, we propose encapsulation of antitumor drugs in nanoparticulated systems. Chitosan (CS) is a naturally occurring polymer that is biocompatibe, biodegradable, non-toxic, cationic and bioadhesive. CS nanoparticles (CS-NPs) have been used as drug carrier for targeted delivery. Titanium dioxide (TiO2), a natural mineral oxide, which is used in biomaterials due to its high stability and antimicrobial and anticorrosive properties. TiO2 showed a potential as a tumor suppressor. In this study a new formulation of MTX loaded in CS NPs (CS-MTX NPs) and coated with Titanium oxide (TiO2) was prepared. The mean particle size, zeta potential, polydispersity index were measured. The interaction between CS NPs and TiO2 NPs was confirmed using FTIR and XRD. CS-MTX NPs was studied in vitro using the tumor cell line MCF-7 (human breast cancer). The results showed that CS-MTX has a size around 169 nm and as they were coated with TiO2, the size ranged between and depending on the ratio of CS-MTX to TiO2 ratio used in the preparation. All NPs (uncoated and coated carried positive charges and were monodispersed. The entrapment efficacy was around 65%. Both FTIR and XRD proved that TiO2 interacted with CS-MTX NPs. The drug invitro release was controlled and sustained over days. Finally, the studied in vitro using the tumor cell line MCF-7 suggested that combining nanomaterials with anticancer drugs CS-MTX NPs may be more effective than free MTX for cancer treatment. In conclusion, the combination of CS-MTX NPs and TiO2 NPs showed excellent time-dependent in vitro antitumor behavior, therefore, can be employed as a promising anticancer agent to attain efficient results towards MCF-7 cells.

Keywords: Methotrexate, Titanium dioxide, Chitosan nanoparticles, cancer

Procedia PDF Downloads 89
1245 Numerical Study on the Performance of Upgraded Victorian Brown Coal in an Ironmaking Blast Furnace

Authors: Junhai Liao, Yansong Shen, Aibing Yu

Abstract:

A 3D numerical model is developed to simulate the complicated in-furnace combustion phenomena in the lower part of an ironmaking blast furnace (BF) while using pulverized coal injection (PCI) technology to reduce the consumption of relatively expensive coke. The computational domain covers blowpipe-tuyere-raceway-coke bed in the BF. The model is validated against experimental data in terms of gaseous compositions and coal burnout. Parameters, such as coal properties and some key operational variables, play an important role on the performance of coal combustion. Their diverse effects on different combustion characteristics are examined in the domain, in terms of gas compositions, temperature, and burnout. The heat generated by the combustion of upgraded Victorian brown coal is able to meet the heating requirement of a BF, hence making upgraded brown coal injected into BF possible. It is evidenced that the model is suitable to investigate the mechanism of the PCI operation in a BF. Prediction results provide scientific insights to optimize and control of the PCI operation. This model cuts the cost to investigate and understand the comprehensive combustion phenomena of upgraded Victorian brown coal in a full-scale BF.

Keywords: blast furnace, numerical study, pulverized coal injection, Victorian brown coal

Procedia PDF Downloads 232
1244 A Smart Monitoring System for Preventing Gas Risks in Indoor

Authors: Gyoutae Park, Geunjun Lyu, Yeonjae Lee, Jaheon Gu, Sanguk Ahn, Hiesik Kim

Abstract:

In this paper, we propose a system for preventing gas risks through the use of wireless communication modules and intelligent gas safety appliances. Our system configuration consists of an automatic extinguishing system, detectors, a wall-pad, and a microcomputer controlled micom gas meter to monitor gas flow and pressure as well as the occurrence of earthquakes. The automatic fire extinguishing system checks for both combustible gaseous leaks and monitors the environmental temperature, while the detector array measures smoke and CO gas concentrations. Depending on detected conditions, the micom gas meter cuts off an inner valve and generates a warning, the automatic fire-extinguishing system cuts off an external valve and sprays extinguishing materials, or the sensors generate signals and take further action when smoke or CO are detected. Information on intelligent measures taken by the gas safety appliances and sensors are transmitted to the wall-pad, which in turn relays this as real time data to a server that can be monitored via an external network (BcN) connection to a web or mobile application for the management of gas safety. To validate this smart-home gas management system, we field-tested its suitability for use in Korean apartments under several scenarios.

Keywords: gas sensor, leak, gas safety, gas meter, gas risk, wireless communication

Procedia PDF Downloads 406
1243 Egyptian Soil Isolate Shows Promise as a Source of a New Broad-spectrum Antimicrobial Agent Against Multidrug-resistant Pathogens

Authors: Norhan H. Mahdally, Bathini Thissera Riham A. ElShiekh, Noha M. Elhosseiny, Mona T. Kashef, Ali M. El Halawany, Mostafa E. Rateb, Ahmed S. Attia

Abstract:

Multidrug-resistant (MDR) pathogens pose a global threat to healthcare settings. The exhaustion of the current antibiotic arsenal and the scarcity of new antimicrobials in the pipeline aggravate this threat and necessitate a prompt and effective response. This study focused on two major pathogens that can cause serious infections: carbapenem-resistant Acinetobacter baumannii (CRAB) and methicillin-resistant Staphylococcus aureus (MRSA). Multiple soil isolates were collected from several locations throughout Egypt and screened for their conventional and non-conventional antimicrobial activities against MDR pathogens. One isolate exhibited potent antimicrobial activity and was subjected to multiple rounds of fractionation. After fermentation and bio-guided fractionation, we identified pure microbial secondary metabolites with two scaffolds that exhibited promising effects against CRAB and MRSA. Scaling up and chemical synthesis of derivatives of the identified metabolite resulted in obtaining a more potent derivative, which we designated as 2HP. Cytotoxicity studies indicated that 2HP is well-tolerated by human cells. Ongoing work is focusing on formulating the new compound into a nano-formulation to enhance its delivery. Also, to have a better idea about how this compound works, a proteomic approach is currently underway. Our findings suggest that 2HP is a potential new broad-spectrum antimicrobial agent. Further studies are needed to confirm these findings and to develop 2HP into a safe and effective treatment for MDR infections.

Keywords: broad-spectrum antimicrobials, carbapenem-resistant acinetobacter baumannii, drug discovery, methicillin-resistant staphylococcus aureus, multidrug-resistant, natural products

Procedia PDF Downloads 66
1242 In Vitro Effects of Azadirachta indica Leaves Extract Against Albugo Candida, the Causative Agent of White Blisters Disease of Brassica Oleraceae L., Var. Italica

Authors: Affiah D. U., Katuri I. P., Emefiene M. E., Amienyo C. A.

Abstract:

Broccoli (Brassica oleraceae L., var. italica) is one of the most important vegetables that is high in nutrients and bioactive compounds. It easily grown on a wide range of soil types and is adaptable to many different climatic conditions. This study was carried out within Jos North and environs in vitro to evaluate Neem (Azadirachta indica) leaves extract against Albugo candida, the causative agent of white blisters disease of broccoli. Through the survey, prevalence and incidence were accessed and a fluffy white growth symptom on the underside of leaves was also observed on the field. Infected leaves samples were collected from three different farms namely: Farin Gada, Naraguta, and Juth and the organism associated with the disease was isolated. Pathogenicity test carried out revealed the fungal isolate Albugo candida to be responsible for the disease. Antimicrobial susceptibility test was performed using agar well diffusion method to determine the minimum inhibitory concentrations of two extract of Azadirachta indica leaves against the organism. Ethanolic extract had the highest antifungal activities of 3.30±0.21 - 17.61± 0.11 while aqueous extract had the least antifungal activities of 0.00±0.00 - 13.23±0.12. The minimum inhibitory concentration of aqueous was 100 mg/ml while its minimum fungicidal concentration was at 200 mg/ml. For ethanol, the minimum inhibitory concentration was 50 mg/ml while its minimum fungicidal concentration was 100 mg/ml. Plants being less toxic in usage over synthetic or inorganic chemicals makes them easy to handle, easily accessible and renewable. Due to the biosafety of plant extracts and its availability since the plant-based extracts of the two different solvents were found to be effective against the test organism hence, it is recommended for in-depth research to make it readily available for control of other pathogens and pests.

Keywords: antifungal, biocontrol, broccoli, fungi

Procedia PDF Downloads 56
1241 The Study of Heat and Mass Transfer for Ferrous Materials' Filtration Drying

Authors: Dmytro Symak

Abstract:

Drying is a complex technologic, thermal and energy process. Energy cost of drying processes in many cases is the most costly stage of production, and can be over 50% of total costs. As we know, in Ukraine over 85% of Portland cement is produced moist, and the finished product energy costs make up to almost 60%. During the wet cement production, energy costs make up over 5500 kJ / kg of clinker, while during the dry only 3100 kJ / kg, that is, switching to a dry Portland cement will allow result into double cutting energy costs. Therefore, to study raw materials drying process in the manufacture of Portland cement is very actual task. The fine ferrous materials drying (small pyrites, red mud, clay Kyoko) is recommended to do by filtration method, that is one of the most intense. The essence of filtration method drying lies in heat agent filtering through a stationary layer of wet material, which is located on the perforated partition, in the "layer-dispersed material - perforated partition." For the optimum drying purposes, it is necessary to establish the dependence of pressure loss in the layer of dispersed material, and the values of heat and mass transfer, depending on the speed of the gas flow filtering. In our research, the experimentally determined pressure loss in the layer of dispersed material was generalized based on dimensionless complexes in the form and coefficients of heat exchange. We also determined the relation between the coefficients of mass and heat transfer. As a result of theoretic and experimental investigations, it was possible to develop a methodology for calculating the optimal parameters for the thermal agent and the main parameters for the filtration drying installation. The comparison of calculated by known operating expenses methods for the process of small pyrites drying in a rotating drum and filtration method shows to save up to 618 kWh per 1,000 kg of dry material and 700 kWh during filtration drying clay.

Keywords: drying, cement, heat and mass transfer, filtration method

Procedia PDF Downloads 249
1240 Development of a Humanized Anti-CEA Antibody for the Near Infrared Optical Imaging of Cancer

Authors: Paul J Yazaki, Michael Bouvet, John Shively

Abstract:

Surgery for solid gastrointestinal (GI) cancers such as pancreatic, colorectal, and gastric adenocarcinoma remains the mainstay of curative therapy. Complete resection of the primary tumor with negative margins (R0 resection), its draining lymph nodes, and distant metastases offers the optimal surgical benefit. Real-time fluorescence guided surgery (FGS) promises to improve GI cancer outcomes and is rapidly advancing with tumor-specific antibody conjugated fluorophores that can be imaged using near infrared (NIR) technology. Carcinoembryonic Antigen (CEA) is a non-internalizing tumor antigen validated as a surface tumor marker expressed in >95% of colorectal, 80% of gastric, and 60% of pancreatic adenocarcinomas. Our humanized anti-CEA hT84.66-M5A (M5A) monoclonal antibody (mAb)was conjugated with the NHS-IRDye800CW fluorophore and shown it can rapidly and effectively NIRoptical imageorthotopically implanted human colon and pancreatic cancer in mouse models. A limitation observed is that these NIR-800 dye conjugated mAbs have a rapid clearance from the blood, leading to a narrow timeframe for FGS and requiring high doses for effective optical imaging. We developed a novel antibody-fluorophore conjugate by incorporating a PEGylated sidearm linker to shield or mask the IR800 dye’s hydrophobicity which effectively extended the agent’s blood circulation half-life leading to increased tumor sensitivity and lowered normal hepatic uptake. We hypothesized that our unique anti-CEA linked to the fluorophore, IR800 by PEGylated sidewinder, M5A-SW-IR800 will become the next generation optical imaging agent, safe, effective, and widely applicable for intraoperative image guided surgery in CEA expressing GI cancers.

Keywords: optical imaging, anti-CEA, cancer, fluorescence-guided surgery

Procedia PDF Downloads 138
1239 Switchable Lipids: From a Molecular Switch to a pH-Sensitive System for the Drug and Gene Delivery

Authors: Jeanne Leblond, Warren Viricel, Amira Mbarek

Abstract:

Although several products have reached the market, gene therapeutics are still in their first stages and require optimization. It is possible to improve their lacking efficiency by the use of carefully engineered vectors, able to carry the genetic material through each of the biological barriers they need to cross. In particular, getting inside the cell is a major challenge, because these hydrophilic nucleic acids have to cross the lipid-rich plasmatic and/or endosomal membrane, before being degraded into lysosomes. It takes less than one hour for newly endocytosed liposomes to reach highly acidic lysosomes, meaning that the degradation of the carried gene occurs rapidly, thus limiting the transfection efficiency. We propose to use a new pH-sensitive lipid able to change its conformation upon protonation at endosomal pH values, leading to the disruption of the lipidic bilayer and thus to the fast release of the nucleic acids into the cytosol. It is expected that this new pH-sensitive mechanism promote endosomal escape of the gene, thereby its transfection efficiency. The main challenge of this work was to design a preparation presenting fast-responding lipidic bilayer destabilization properties at endosomal pH 5 while remaining stable at blood pH value and during storage. A series of pH-sensitive lipids able to perform a conformational switch upon acidification were designed and synthesized. Liposomes containing these switchable lipids, as well as co-lipids were prepared and characterized. The liposomes were stable at 4°C and pH 7.4 for several months. Incubation with siRNA led to the full entrapment of nucleic acids as soon as the positive/negative charge ratio was superior to 2. The best liposomal formulation demonstrated a silencing efficiency up to 10% on HeLa cells, very similar to a commercial agent, with a lowest toxicity than the commercial agent. Using flow cytometry and microscopy assays, we demonstrated that drop of pH was required for the transfection efficiency, since bafilomycin blocked the transfection efficiency. Additional evidence was brought by the synthesis of a negative control lipid, which was unable to switch its conformation, and consequently exhibited no transfection ability. Mechanistic studies revealed that the uptake was mediated through endocytosis, by clathrin and caveolae pathways, as reported for previous lipid nanoparticle systems. This potent system was used for the treatment of hypercholesterolemia. The switchable lipids were able to knockdown PCSK9 expression on human hepatocytes (Huh-7). Its efficiency is currently evaluated on in vivo mice model of PCSK9 KO mice. In summary, we designed and optimized a new cationic pH-sensitive lipid for gene delivery. Its transfection efficiency is similar to the best available commercial agent, without the usually associated toxicity. The promising results lead to its use for the treatment of hypercholesterolemia on a mice model. Anticancer applications and pulmonary chronic disease are also currently investigated.

Keywords: liposomes, siRNA, pH-sensitive, molecular switch

Procedia PDF Downloads 195
1238 Versatile Variation of Fischer Indolization in Green Synthesis of Nitro Substituted Tetrahydrocarbazole

Authors: Zubi Sadiq, Ghazala Yaqub, Almas Hamid

Abstract:

We wish to report herein a very stimulating variation in Fischer indole reaction by adopting solvent and catalyst free conditions. A concise synthesis of dinitro tetrahydrocarbazole derivative 3 was introduced without the use of any accelerating agent at ambient temperature with fairly good yield. Product was fully corroborated by UV, FTIR, 1H NMR, 13C NMR, MS, and CHN analysis.

Keywords: fischer indole reaction, neutral medium, solvent free synthesis, tetrahydrocarbazole

Procedia PDF Downloads 343