Search results for: pan drug resistance

Authors: Azza H. El-Medany, Hanan H. Hagar, Omnia A. Nayel, Jamila H. El-Medany

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In search for drugs that can target cancer cell micro-environment in as much as being able to halt malignant cellular transformation, the natural dietary phytochemical curcumin was currently assessed in DMH-induced colorectal cancer rat model. The study enrolled 50 animals divided into a control group (n=10) and DMH-induced colorectal cancer control group (n=20) (20mg/kg-body weight for 28 weeks) versus curcumin-treated group (n=20) (160 mg/kg suspension daily oral for further 8 weeks). Treatment by curcumin succeeded to significantly decrease the percent of ACF and tended to normalize back the histological changes retrieved in adenomatous and stromal cells induced by DMH. The drug also significantly elevated GSH and significantly reduced most of the accompanying biochemical elevations (namely MDA, TNF-α, TGF-β and COX2) observed in colonic carcinomatous tissue, induced by DMH, thus succeeding to revert that of MDA, COX2 and TGF-β back to near normal as justified by being non-significantly altered as compared to normal controls. The only exception was PAF that was insignificantly altered by the drug. When taken together, it could be concluded that curcumin possess the potentiality to halt some of the orchestrated cross-talk between cancerous transformation and its micro-environmental niche that contributes to cancer initiation, progression and metastasis in this experimental cancer colon model. Envisioning these merits to a drug with already known safety preferentiality, awaits final results of current ongoing clinical trials, before curcumin can be added to the new therapeutic armamentarium of anticancer therapy.

Keywords: curcumin, dimethyl hydralazine, aberrant crypt foci, malondialdehyde, reduced glutathione, cyclooxygenase-2, tumour necrosis factor-alpha, transforming growth factor-beta, platelet activating factor

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Authors: Kalaumari Mayoral-Peña, Ana I. Montejano-Montelongo, Josué Reyes-Muñoz, Gonzalo A. Ortiz-Mancilla, Mayrin Rodríguez-Cruz, Víctor Hernández-Villalobos, Jesús A. Guzmán-López, Santiago García-Jacobo, Iván Licona-Vázquez, Grisel Fierros-Romero, Rosario Flores-Vallejo

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The group B-lactamic antibiotics include some of the most frequently used small drug molecules against bacterial infections. Nevertheless, an alarming decrease in their efficacy has been reported due to the emergence of antibiotic-resistant bacteria. Infections caused by bacteria expressing extended Spectrum B-lactamases (ESBLs) are difficult to treat and account for higher morbidity and mortality rates, delayed recovery, and high economic burden. According to the Global Report on Antimicrobial Resistance Surveillance, it is estimated that mortality due to resistant bacteria will ascend to 10 million cases per year worldwide. These facts highlight the importance of developing low-cost and readily accessible detection methods of drug-resistant ESBLs bacteria to prevent their spread and promote accurate and fast diagnosis. Bacterial detection is commonly done using molecular diagnostic techniques, where PCR stands out for its high performance. However, this technique requires specialized equipment not available everywhere, is time-consuming, and has a high cost. Loop-Mediated Isothermal Amplification (LAMP) is an alternative technique that works at a constant temperature, significantly decreasing the equipment cost. It yields double-stranded DNA of several lengths with repetitions of the target DNA sequence as a product. Although positive and negative results from LAMP can be discriminated by colorimetry, fluorescence, and turbidity, there is still a large room for improvement in the point-of-care implementation. DNA origami is a technique that allows the formation of 3D nanometric structures by folding a large single-stranded DNA (scaffold) into a determined shape with the help of short DNA sequences (staples), which hybridize with the scaffold. This research aimed to generate DNA origami structures using LAMP products as scaffolds to improve the sensitivity to detect ESBLs in point-of-care diagnosis. For this study, the coding sequence of the CTM-X-15 ESBL of E. coli was used to generate the LAMP products. The set of LAMP primers were designed using PrimerExplorerV5. As a result, a target sequence of 200 nucleotides from CTM-X-15 ESBL was obtained. Afterward, eight different DNA origami structures were designed using the target sequence in the SDCadnano and analyzed with CanDo to evaluate the stability of the 3D structures. The designs were constructed minimizing the total number of staples to reduce costs and complexity for point-of-care applications. After analyzing the DNA origami designs, two structures were selected. The first one was a zig-zag flat structure, while the second one was a wall-like shape. Given the sequence repetitions in the scaffold sequence, both were able to be assembled with only 6 different staples each one, ranging between 18 to 80 nucleotides. Simulations of both structures were performed using scaffolds of different sizes yielding stable structures in all the cases. The generation of the LAMP products were tested by colorimetry and electrophoresis. The formation of the DNA structures was analyzed using electrophoresis and colorimetry. The modeling of novel detection methods through bioinformatics tools allows reliable control and prediction of results. To our knowledge, this is the first study that uses LAMP products and DNA-origami in combination to delect ESBL-producing bacterial strains, which represent a promising methodology for diagnosis in the point-of-care.

Keywords: beta-lactamases, antibiotic resistance, DNA origami, isothermal amplification, LAMP technique, molecular diagnosis

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Authors: Nehal Adel Khalil, Amel Foad Ketat, Fairouz Elsayed Mohamed Ali, Nahla Abdelmoneim Hamid, Hazem Farag Manaa

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Background: Chronic myeloid leukemia (CML) represents 15% of adult leukemias. Imatinib Mesylate (IM) is the gold standard treatment for new cases of CML. Treatment with IM results in improvement of the majority of cases. However, about 25% of cases may develop resistance. Sensitive and specific early predictors of IM resistance in CML patients have not been established to date. Aim: To investigate the value of miR-451 in CML as an early predictor for IM resistance in Egyptian CML patients. Methods: The study employed Real time Polymerase Reaction (qPCR) technique to investigate the leucocytic expression of miR-451 in fifteen newly diagnosed CML patients (group I), fifteen IM responder CML patients (group II), fifteen IM resistant CML patients (group III) and fifteen healthy subjects of matched age and sex as a control group (group IV). The response to IM was defined as < 10% BCR-ABL transcript level after 3 months of therapy. The following parameters were assessed in subjects of all the studied groups: 1- Complete blood count (CBC). 2- Measurement of plasma level of miRNA 451 using real-time Polymerase Chain Reaction (qPCR). 3- Detection of BCR-ABL gene mutation in CML using qPCR. Results: The present study revealed that miR-451 was significantly down-regulated in leucocytes of newly diagnosed CML patients as compared to healthy subjects. IM responder CML patients showed an up-regulation of miR- 451 compared with IM resistant CML patients. Conclusion: According to the data from the present study, it can be concluded that leucocytic miR- 451 expression is a useful additional follow-up marker for the response to IM and a promising prognostic biomarker for CML.

Keywords: chronic myeloid leukemia, imatinib resistance, microRNA 451, Polymerase Chain Reaction

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Authors: Merzak Laribi, Abdelmadjid Kasser

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Thermal spraying processes are widely used to produce coatings on original constructions as well as in repair and maintenance of long standing structures. A lot of efforts forwarding to develop thermal spray coatings technology have been focused on improving mechanical characteristics, minimizing residual stress level and reducing porosity of the coatings. The specific aim of this paper is to determine either residual stresses distribution or wear resistance of stainless steel coating thermally sprayed on a carbon steel substrate. Internal stresses determination was performed using an extensometric method in combination with a simultaneous progressive electrolytic polishing. The procedure consists of measuring micro-deformations using a bi-directional extensometric gauges glued on the substrate side of the materials. Very thin layers of the deposits are removed by electrochemical polishing across the sample surface. Micro-deformations are instantaneously measured, leading to residual stresses calculation after each removal. Wear resistance of the coating has been determined using a ball-on-plate tribometer. Friction coefficient is instantaneously measured during the tribological test. Attention was particularly focused on the influence of a post-annealing at 850 °C for one hour in vacuum either on the residual stresses distribution or on the wear resistance behavior under specific wear and lubrication conditions. The obtained results showed that the microstructure of the obtained arc sprayed stainless steel coating is classical. It is homogeneous and contains un-melted particles, metallic oxides and also pores and micro-cracks. The internal stresses are in compression in the coating. They are more or less scattered between -50 and -270 MPa on the surface and decreased more at the interface. The value at the surface of the substrate is about –700 MPa, partially due to the molten particles impact with the substrate. The post annealing has reduced the residual stresses in both coating and surface of the steel substrate so that the hole material becomes more relaxed. Friction coefficient has an average value of 0.3 and 0.4 respectively for non annealed and annealed specimen. It is rather oil lubrication which is really benefit so that friction coefficient is decreased to about 0.06.

Keywords: residual stresses, wear resistance, stainless steel, coating, thermal spraying, annealing, lubrication

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Authors: Ahmed Jibrin Uttu, Maimuna Waziri

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The root bark of Glossonema boveanum (Decne), a member of Apocynaceae family, is used by traditional medicine practitioner to treat urinary and respiratory tract infections, bacteremia, typhoid fever, bacillary dysentery, diarrhea and stomach pain. This present study aims to validate the medicinal claims ascribed to the root bark of the plant. Preliminary phytochemical study of the root bark extracts (n-hexane, ethyl acetate, chloroform and methanol extracts) showed the presence of alkaloids, carbohydrates, steroids, triterpenes, cardiac glycosides, saponins, tannins and flavonoids. Antimicrobial study of the extracts showed activities against Staphylococus aureus, Bacillus subtilis, Salmonella typhii, Shigella dysenteriae, Escherichia coli, Enterobacter cloacae, Streptococcus agalactiae and Candida albicans while Micrococcus luteus, Pseudomonas aeruginosa and Klebsiella Pneumoniae showed resistance to all the extracts. The inhibitory effect was compared with the standard drug ciprofloxacin and fluconazole. MIC and MBC for both extracts were also determined using the tube dilution method. This study concluded that the root bark of G. boveanum, used traditionally as a medicinal plant, has antimicrobial activities against some causative organisms.

Keywords: Glossonema boveanum (Decne.), phytochemical, antimicrobial, minimum inhibitory concentration, minimum bactericidal concentration

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Authors: Faraz Zarghami, Elham Anari, Nosratollah Zarghami, Yones Pilehvar-Soltanahmadi, Abolfazl Akbarzadeh, Sepideh Jalilzadeh-Tabrizi

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The development of nanotherapy has presented a new method of drug delivery targeted directly to the neoplasmic tissues, to maximize the action with fewer dose requirements. In the past two decades, poly(lactic-co-glycolic acid) (PLGA) has frequently been investigated by many researchers and is a popular polymeric candidate, due to its biocompatibility and biodegradability, exhibition of a wide range of erosion times, tunable mechanical properties, and most notably, because it is a FDA-approved polymer. Chrysin is a natural flavonoid which has been reported to have some significant biological effects on the processes of chemical defense, nitrogen fixation, inflammation, and oxidation. However, the low solubility in water decreases its bioavailability and consequently disrupts the biomedical benefits. Being loaded with PLGA-PEG increases chrysin solubility and drug tolerance, and decreases the discordant effects of the drug. The well-structured chrysin efficiently accumulates in the breast cancer cell line (T47D). In the present study, the structure and chrysin loading were delineated using proton nuclear magnetic resonance (HNMR), Fourier-transform infrared spectroscopy (FT-IR), and scanning electron microscopy (SEM), and the in vitro cytotoxicity of pure and nanochrysin was studied by the MTT assay. Next, the RNA was exploited and the cytotoxic effects of chrysin were studied by real-time PCR. In conclusion, the nanochrysin therapy developed is a novel method that could increase cytotoxicity to cancer cells without damaging the normal cells, and would be promising in breast cancer therapy.

Keywords: MTT assay, chrysin, flavonoids, nanotherapy

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Authors: Ralph Gruber, Martina Hafner, Theresia Greunz, Christian Reisecker, David Stifter

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The application of dry lubricant on aluminium for automotive industry is indispensable for a high-quality forming behaviour. To provide a short production time those forming aids will not be removed during the joining step. The aim of this study was the characterization of the influence of dry lubricants on the bond strength and the corrosion resistance of an 6xxx aluminium alloy for automotive applications. For this purpose, samples with a well-defined surface were lubricated with 1 g/m² dry lubricant and joined with a commercial thermosetting 1K-epoxy structural adhesive. The bond strength was characterized by means of lap shear test. To evaluate the corrosion resistance of the adhered aluminium samples an immersion test in 5 w% NaCl-solution was used. Based on fracture pattern analysis, the corrosion behaviour could be described. Dissolved corrosion products were examined using ICP-MS and NMR. By means of SEM/EDX the elementary composition of precipitated solids was determined. The results showed a dry lubricant independent bond strength for standard testing conditions. However, a significant effect of the forming aid, regarding the corrosion resistance of adhered aluminium samples against corrosive infiltration of the metal-adhesive-interface, was observed

Keywords: aluminium alloys, dry film lubricants, automotive industry, adhesive bonding, corrosion

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Authors: Mhaned Oubounyt, Jan Baumbach

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Differences in co-expression networks between two or multiple cells (sub)types across conditions is a pressing problem in single-cell RNA sequencing (scRNA-seq). A key challenge is to define those co-variations that differ between or among cell types and/or conditions and phenotypes to examine small regulatory networks that can explain mechanistic differences. To this end, we developed SCANet, an all-in-one Python package that uses state-of-the-art algorithms to facilitate the workflow of a combined single-cell GCN (Gene Correlation Network) and GRN (Gene Regulatory Networks) pipeline, including inference of gene co-expression modules from scRNA-seq, followed by trait and cell type associations, hub gene detection, co-regulatory networks, and drug-gene interactions. In an example case, we illustrate how SCANet can be applied to identify regulatory drivers behind a cytokine storm associated with mortality in patients with acute respiratory illness. SCANet is available as a free, open-source, and user-friendly Python package that can be easily integrated into systems biology pipelines.

Keywords: single-cell, co-expression networks, drug-gene interactions, co-regulatory networks

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Authors: J. S. P. Barbosa, L. C. Pereira, K. R. Garcia, P. C. P. Bouchardet, S. C. T. Vieira, A. O. Gomes, S. S. Funghetto, M. G. O. Kanikowski

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For this population, height seems to be a good predictor of strength and body composition. This increase in life expectancy of the Brazilian's population is associated with sociodemographic variables, but also to more access to health services in the prevention and better living conditions. With the growth of elderly population, a problem that has been a concern to health's professionals and public health at all is the use of psychoactive substances. The purpose of this study was to identify the sociodemographic profile of the elderly people who was attended at the Center of Psychosocial Care of alcohol and other drugs in the Federal District of Brazil. 408 medical records of people aged 60 years or over were evaluated, and it is possible to know that most of them were males (85.3%), with a mean age of 64 years (DP ± 4.16), 60 and 84 years and a mean age of 64 years (DP ± 4.42); 88.2% have some family ties, are married and have children, with relatives living in masonry housing. The educational level of drug users was considered low with more emphasis on those who had elementary education being the majority retired or unemployed. Regarding the street situation, there was no significance (p = 0.084), and the women (OR = 2.98) had few chances of street situations compared to men (OR = 0.89). As for substance consumption, the highest quantity of drug consumption bids in relation to the number of illicit. It did not present significant statistical value, and there is a greater probability of consumption/abuse of legal and/or illicit drugs for both sexes (OR = 0.96) for men and (OR = 1.32) for women. In relation to the use of multiple drugs, there was no significant difference between the sexes, (OR = 1.1) male sex and (OR = 0.74) female sex. Based on the results found in the present study, it was concluded that alcohol consumption is the main agent that causes vulnerability in the elderly and predisposes the latter to the consumption of other associated drugs.

Keywords: centers of attention psychosocial alcohol and drugs, elderly, mental disorder due to drug use, street situations

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Authors: Cynthia K. Burzell

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Aequor's Founder, a Marine and Medical Microbiologist, discovered novel, non-toxic chemicals in the ocean that uniquely remove biofilm in minutes and prevent its formation for days. These chemicals and over 70 synthesized analogs that Aequor developed can replace thousands of toxic biocides used in consumer and industrial products and, as new drug candidates, kill biofilm-forming bacteria and fungi Superbugs -the antimicrobial-resistant (AMR) pathogens for which there is no cure. Cynthia Burzell, PhD., is a Marine and Medical Microbiologist studying natural mechanisms that inhibit biofilm formation on surfaces in contact with water. In 2002, she discovered a new genus and several new species of marine microbes that produce small molecules that remove biofilm in minutes and prevent its formation for days. The molecules include new antimicrobials that can replace thousands of toxic biocides used in consumer and industrial products and can be developed into new drug candidates to kill the biofilm-forming bacteria and fungi -- including the antimicrobial-resistant (AMR) Superbugs for which there is no cure. Today, Aequor has over 70 chemicals that are divided into categories: (1) Novel natural chemicals. Lonza validated that the primary natural chemical removed biofilm in minutes and stated: "Nothing else known can do this at non-toxic doses." (2) Specialty chemicals. 25 of these structural analogs are already approved under the U.S. Environmental Protection Agency (EPA)'s Toxic Substances Control Act, certified as "green" and available for immediate sale. These have been validated for the following agro-industrial verticals: (a) Surface cleaners: The U.S. Department of Agriculture validated that low concentrations of Aequor's formulations provide deep cleaning of inert, nano and organic surfaces and materials; (b) Water treatments: NASA validated that one dose of Aequor's treatment in the International Space Station's water reuse/recycling system lasted 15 months without replenishment. DOE validated that our treatments lower energy consumption by over 10% in buildings and industrial processes. Future validations include pilot projects with the EPA to test efficacy in hospital plumbing systems. (c) Algae cultivation and yeast fermentation: The U.S. Department of Energy (DOE) validated that Aequor's treatment boosted biomass of renewable feedstocks by 40% in half the time -- increasing the profitability of biofuels and biobased co-products. DOE also validated increased yields and crop protection of algae under cultivation in open ponds. A private oil and gas company validated decontamination of oilfield water. (3) New structural analogs. These kill Gram-negative and Gram-positive bacteria and fungi alone, in combinations with each other, and in combination with low doses of existing, ineffective antibiotics (including Penicillin), "potentiating" them to kill AMR pathogens at doses too low to trigger resistance. Both the U.S. National Institutes for Health (NIH) and Department of Defense (DOD) has executed contracts with Aequor to provide the pre-clinical trials needed for these new drug candidates to enter the regulatory approval pipelines. Aequor seeks partners/licensees to commercialize its specialty chemicals and support to evaluate the optimal methods to scale-up of several new structural analogs via activity-guided fractionation and/or biosynthesis in order to initiate the NIH and DOD pre-clinical trials.

Keywords: biofilm, potentiation, prevention, removal

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Authors: Takuya Suzuki, Atsushi Shirai, Takashi Seki

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Acupuncture therapy is one of the treatments in traditional Chinese medicine. Recently, some reports have shown the effectiveness of acupuncture. However, its full acceptance has been hindered by the lack of understanding on mechanism of the therapy. Acupuncture applied to Zusanli (ST-36) enhances blood flow volume in superior mesenteric artery (SMA), yielding peripheral vascular resistance – regulated blood flow of SMA dominated by the parasympathetic system and inhibition of sympathetic system. In this study, a lumped-parameter approximation model of blood flow in the systemic arteries was developed. This model was extremely simple, consisting of the aorta, carotid arteries, arteries of the four limbs and SMA, and their peripheral vascular resistances. Here, the individual artery was simplified to a tapered tube and the resistances were modelled by a linear resistance. We numerically investigated contribution of the peripheral vascular resistance of SMA to the systemic blood distribution using this model. In addition to the upstream end of the model, which correlates with the left ventricle, two types of boundary condition were applied; mean left ventricular pressure which correlates with blood pressure (BP) and mean cardiac output which corresponds to cardiac index (CI). We examined it to reproduce the experimentally obtained hemodynamic change, in terms of the ratio of the aforementioned hemodynamic parameters from their initial values before the acupuncture, by regulating the peripheral vascular resistances and the upstream boundary condition. First, only the peripheral vascular resistance of SMA was changed to show contribution of the resistance to the change in blood flow volume in SMA, expecting reproduction of the experimentally obtained change. It was found, however, this was not enough to reproduce the experimental result. Then, we also changed the resistances of the other arteries together with the value given at upstream boundary. Here, the resistances of the other arteries were changed simultaneously in the same amount. Consequently, we successfully reproduced the hemodynamic change to find that regulation of the upstream boundary condition to the value experimentally obtained after the stimulation is necessary for the reproduction, though statistically significant changes in BP and CI were not observed in the experiment. It is generally known that sympathetic and parasympathetic tones take part in regulation of whole the systemic circulation including the cardiac function. The present result indicates that stimulation to ST-36 could induce vasodilation of peripheral circulation of SMA and vasoconstriction of that of other arteries. In addition, it implies that experimentally obtained small changes in BP and CI induced by the acupuncture may be involved in the therapeutic response.

Keywords: acupuncture, hemodynamics, lumped-parameter approximation, modeling, systemic vascular resistance

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Authors: Amlan Kumar Das, Avinash Marwal, Vikram Pareek

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Liposome plays an important role in medical and pharmaceutical science as e.g. nano scale drug carriers. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment. Magnet-driven liposome used for the targeted delivery of drugs to organs and tissues1. These liposome preparations contain encapsulated drug components and finely dispersed magnetic particles. Liposomes are vesicles of varying size consisting of a spherical lipid bilayer and an aqueous inner compartment that are generated in vitro. These are useful in terms of biocompatibility, biodegradability, and low toxicity, and can control biodistribution by changing the size, lipid composition, and physical characteristics2. Furthermore, liposomes can entrap both hydrophobic and hydrophilic drugs and are able to continuously release the entrapped substrate, thus being useful drug carriers. Magnetic liposomes (MLs) are phospholipid vesicles that encapsulate magneticor paramagnetic nanoparticles. They are applied as contrast agents for magnetic resonance imaging (MRI)3. The biological synthesis of nanoparticles using plant extracts plays an important role in the field of nanotechnology4. Green-synthesized magnetite nanoparticles-protein hybrid has been produced by treating Iron (III)/Iron(II) chloride with the leaf extract of Dhatura Inoxia. The phytochemicals present in the leaf extracts act as a reducing as well stabilizing agents preventing agglomeration, which include flavonoids, phenolic compounds, cardiac glycosides, proteins and sugars. The magnetite nanoparticles-protein hybrid has been trapped inside the aqueous core of the liposome prepared by reversed phase evaporation (REV) method using oleic and linoleic acid which has been shown to be driven under magnetic field confirming the formation magnetic liposome (ML). Chemical characterization of stealth magnetic liposome has been performed by breaking the liposome and release of magnetic nanoparticles. The presence iron has been confirmed by colour complex formation with KSCN and UV-Vis study using spectrophotometer Cary 60, Agilent. This magnet driven liposome using nanoparticles-protein hybrid can be a smart vesicles for the targeted drug delivery.

Keywords: nanoparticles-protein hybrid, magnetic liposome, medical, pharmaceutical science

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Authors: Ravi R. Patel, Vasudev R. Thakkar

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Use of plant growth-promoting rhizobacteria (PGPR) to increase the production and decrees disease occurrence is a recent method in agriculture. An RA2 rhizospheric culture was isolated from peanut rhizosphere from Junagadh region of Gujarat, India and showed different direct and indirect plant growth promoting activity like indole acetic acid, gibberellic acid, siderophore, hydrogen cyanide, Ammonia and (1-Aminocyclopropane-1-Carboxylate) deaminase production, N2 fixation, phosphate and potassium solubilization in vitro. RA2 was able to protect peanut germinating seedling from A. niger infection and reduce collar rot disease incidence 60-35% to 72-41% and increase germination percentage from 70-82% to 75-97% in two varieties GG20 and GG2 of peanut. RA2 was found to induce resistance in A. hypogaea L. seedlings via induction of different defense-related enzymes like phenylalanine ammonia lyase, peroxidase, polyphenol oxidase, lipoxygenase and pathogenesis related protein like chitinase, ß – 1,3- glucanase. Jasmonic acid one of the major signaling molecules of inducing systemic resistance was also found to induced due to RA2 treatments. RA2 bacterium was also promoting peanut growth and reduce A. niger infection in pot studies. 16S rDNA sequence of RA2 showed 99 % homology to Azotobacter species.

Keywords: plant growth promoting rhizobacteria, peanut, aspergillus niger, induce systemic resistance

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Authors: N. Khursheed, M. Fatima, S. Jamal, A. Raza, S. Rattani, Q. Ahsan, A. Rasheed, M. Jawed

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Introduction: Antibiotics are among the commonly prescribed medicines to treat bacterial infections. Their misuse intensifies resistance, and overuse incurs heavy losses to the healthcare system in terms of increased treatment costs and enhanced disease burden. Studies show that 40% of empirically used antibiotics are irrationally utilized. The objective of this study was to evaluate prescribing pattern of antibiotics at six public sector tertiary care hospitals across Pakistan. Methods: A multicenter cross-sectional point prevalence survey (PPS) was conducted in selected wards of six public sector tertiary care hospitals in Pakistan as part of the Clinical Engagement program by Fleming Fund Country Grant Pakistan in collaboration with Indus Hospital & Health Network (IHHN) from February to March 2021, these included Jinnah Postgraduate Medical Center and Dr. Ruth K. M. Pfau Civil Hospital from Karachi, Sheikh Zayed Hospital Lahore, Nishtar Medical University Hospital Multan, Medical Teaching Institute Hayatabad Medical Complex Peshawar, and Provincial Headquarters Hospital Gilgit. WHO PPS methodology was used for data collection (Hospital, ward, and patient level data was collected). Data was entered into the open-source Kobo Collect application and was analyzed using SPSS (version 22.0). Findings: Medical records of 837 in-patients were surveyed, of which the prevalence of antibiotics use was 78.5%. The most commonly prescribed antimicrobial was Ceftriaxone (21.7%) which is categorized in the Watch group of WHO AWaRe Classification, followed by Metronidazole (17.3%), Cefoperazone/Sulbactam (8.4%), Co-Amoxiclav (6.3%) and Piperacillin/Tazobactam (5.9%). The antibiotics were prescribed largely for surgical prophylaxis (36.7%), followed by community-acquired infections (24.7%). One antibiotic was prescribed to 46.7%, two to 39.9%, and three or more to 12.5 %. Two of six (30%) hospitals had functional drug and therapeutic committees, three (50%) had infection prevention and control committees, and one facility had an antibiotic formulary. Conclusion: Findings demonstrate high consumption of broad-spectrum antimicrobials and emphasizes the importance of expanding the antimicrobial stewardship program. Mentoring clinical teams will help to rationalize antimicrobial use.

Keywords: antimicrobial resistance, antimicrobial stewardship, point prevalence survey, antibiotics

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Authors: Frank Jaksoni Mweta, Nozomu Adachi, Yoshikazu Todaka, Hirokazu Sato, Yuta Sato, Hiromi Miura, Masakazu Kobayashi, Chihiro Watanabe, Yoshiteru Aoyagi

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Advances in the consumption of hydrogen fuel increase demands of high strength steel pipes and storage tanks. However, high strength steels are highly sensitive to hydrogen embrittlement. Because the introduction of hydrogen into steel during the fabrication process or from the environment is unavoidable, it is essential to improve hydrogen embrittlement resistance of high strength steels through microstructural control. In the present study, the heterogeneous nanostructure with a tensile strength of about 1.8 GPa and the homogeneous nanostructure with a tensile strength of about 2.0 GPa of 316LN steels were generated after 92% heavy cold rolling and high-pressure torsion straining, respectively. The heterogeneous nanostructure is composed of twin domains, shear bands, and lamellar grains. The homogeneous nanostructure is composed of uniformly distributed ultrafine nanograins. The influence of heterogeneous and homogenous nanostructures on the hydrogen embrittlement resistance was investigated. The specimen for each nanostructure was electrochemically charged with hydrogen for 3, 6, 12, and 24 hours, respectively. Under the same hydrogen charging time, both nanostructures show almost the same concentration of the diffusible hydrogen based on the thermal desorption analysis. The tensile properties of the homogenous nanostructure were severely affected by the diffusible hydrogen. However, the diffusible hydrogen shows less impact on the tensile properties of the heterogeneous nanostructure. The difference in embrittlement behavior between the heterogeneous and homogeneous nanostructures was elucidated based on the mechanism of the cracks' growth observed in the tensile fractography. The hydrogen embrittlement was suppressed in the heterogeneous nanostructure because the twin domain became an obstacle for crack growth. The homogeneous nanostructure was not consisting an obstacle such as a twin domain; thus, the crack growth resistance was low in this nanostructure.

Keywords: diffusible hydrogen, heterogeneous nanostructure, homogeneous nanostructure, hydrogen embrittlement

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Authors: Farrokh Taherkhani, Thomas Pinger, Max Gündel

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The total economic damage caused by corrosion in Germany is estimated to be more than 3% of the GDP per year. Additionally, corrosion and suitable corrosion protection systems are also significant factors in the consideration of life cycle costs for steel hydraulic structures. In addition to classic coating systems (for example, epoxy resin or polyurethane), zinc and its alloys offer effective and very durable corrosion protection for steels. As a protective layer, hot-dip galvanizing prevents the corrosive media from penetrating into the steel matrix and acts as a sacrificial anode, which corrodes in preference to the steel. However, hot-dip galvanizing as a corrosion protection system has not yet been approved by the relevant authority, the Federal Waterways Engineering and Research Institute (BAW) in Germany. In order to make hot-dip galvanizing usable as a corrosion protection system for steel hydraulic structures in the future, different factors must be considered. These factors are (i) corrosion protection type, (ii) resistance to mechanical stress (i.e., abrasion resistance), (iii) combinability with cathodic corrosion protection, (iv) environmental effects and (v) the crack formation and propagation during hot-dip galvanizing. In this work, hot-dip galvanizing as a corrosion protection system for steel hydraulic steel structures, as well as open questions, are discussed. This paper is based on initial long-term exposure tests with corrosion protection systems consisting of hot-dip galvanizing and duplex systems.

Keywords: steel hydraulic structure, hot-dip galvanizing, corrosion, corrosion resistance, zinc coating, organic coating, duplex sytems

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Authors: A. Zatir, A. Mokhtari, A. Foufa, S. Zatir

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The city of Oran, like any other region of northern Algeria, is subject to frequent seismic activity, the study presented in this work will be based on an analysis of urban and architectural context of the city of Oran before the date of the earthquake of 1790, and then try to deduce the differences between the old city before and after the earthquake. The analysis developed as a specific objective to tap into the seismic history of the city of Oran parallel to its urban history. The example of the citadel of Oran indicates that constructions presenting the site of the old citadel, may present elements of resistance for face to seismic effects. Removed in city observations of these structures, showed the ingenuity of the techniques used by the ancient builders, including the good performance of domes and arches in resistance to seismic forces.

Keywords: earthquake, citadel, performance, traditional techniques, constructions

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Authors: Ping Ren, Mao Wen, Kan Zhang, Weitao Zheng

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The improvement of comprehensive properties including hardness, toughness, wear, and corrosion resistance in the transition metal carbides/nitrides TMCN films, especially avoiding the trade-off between hardness and toughness, is strongly required to adapt to various applications. Although incorporating ductile metal DM phase into the TMCN via thermally-induced phase separation has been emerged as an effective approach to toughen TMCN-based films, the DM is just limited to some soft ductile metal (i.e. Cu, Ag, Au immiscibility with the TMCN. Moreover, hardness is highly sensitive to soft DM content and can be significantly worsened. Hence, a novel preparation method should be attempted to broaden the DM selection and assemble much more ordered nanocomposite structure for improving the comprehensive properties. Here, we provide a new strategy, by activating solid-state dewetting during layered deposition, to accomplish the self-assembly of ordered TaC@Ta core-shell-like nanocomposite film consisting of TaC nanocrystalline encapsulated with thin pseudocrystal Ta tissue. That results in the superhard (~45.1 GPa) dominated by Orowan strengthening mechanism and high toughness attributed to indenter-induced phase transformation from the pseudocrystal to body-centered cubic Ta, together with the drastically enhanced wear and corrosion resistance. Furthermore, very thin pseudocrystal Ta encapsulated layer (~1.5 nm) in the TaC@Ta core-shell-like structure helps for promoting the formation of lubricious TaOₓ Magnéli phase during sliding, thereby further dropping the coefficient of friction. Apparently, solid-state dewetting may provide a new route to construct ordered TMC(N)@TM core-shell-like nanocomposite capable of combining superhard, high toughness, low friction, superior wear with corrosion resistance.

Keywords: corrosion, nanocomposite film, solid-state dewetting, tribology

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Authors: Tamrat Girma Biru

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Multidrug-resistant tuberculosis (MDR-TB) is defined as resistant to at least Refampicin and Isoniazed: the most two power full TB drugs. It is a leading cause of high rates of morbidity and mortality, and increasing psychosocial challenges to patients, especially when co-infected with Human Immunodeficiency Virus (HIV). Ethiopia faces the highest rates of MDR-TB infection in the world. Objectives: The main objective of this study was to identify the psychosocial challenges of MDR-TB patients, to investigate the extent of the psychosocial challenges on (self-esteem, depression, and stigma) that MDR-TB patients encounter, to examine whether there is a sex difference in experiencing psychosocial challenges and assess the counseling needs of MDR-TB patients. Methodology: A cross-sectional study was conducted at St. Peter TB Specialized Hospital, Addis Ababa on 40 patients (25 males and 15 females) who are hospitalized for treatment. The patients were identified by using purposive sampling and made fill a questionnaire measuring their level of self-esteem, depression and stigma. Besides, data were collected from 16 participants, 28 care providers and 8 guardians, using semi-structured interview. The obtained data were analyzed using SPSS statistical program, descriptive statistics, independent t-test, and qualitative description. Results and Discussion: The results of the study showed that the majority (80%) of the respondents had suffered psychological challenges and social discriminations. Thus, the significance of MDR-TB and its association with HIV/AIDS problems is considered. Besides the psychosocial challenges, various aggravating factors such as length of treatment, drug burden and insecurity in economy together highly challenges the life of patients. In addition, 60% of participants showed low level of self-esteem. The patients also reported that they experienced high self-stigma and stigma by other members of the society. The majority of the participants (75%) showed moderate and severe level of depression. In terms of sex there is no difference between the mean scores of males and females in the level of depression and stigmatization by others and by themselves. But females showed lower level of self-esteem than males. The analysis of the t-test also shows that there were no statistically significant sex difference on the level of depression and stigma. Based on the qualitative data MDR-TB patients face various challenges in their life sphere such as: Psychological (depression, low self value, lowliness, anxiety), social (stigma, isolation from social relations, self-stigmatization,) and medical (drug side effect, drug toxicity, drug burden, treatment length, hospital stays). Recommendations: Based on the findings of this study possible recommendations were forwarded: develop and extend MDR-TB disease awareness creation through by media (printing and electronic), school net TB clubs, and door to door community education. Strengthen psychological wellbeing and social relationship of MDR-TB patients using proper and consistent psychosocial support and counseling. Responsible bodies like Ministry of Health (MOH) and its stakeholders and Non Governmental Organizations (NGOs) need to assess the challenges of patients and take measures on this pressing issue.

Keywords: psychosocial challenges, counseling, multi-drug resistant tuberculosis (MDR-TB), tuberculosis therapy

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Authors: Josie West

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This paper focuses on the conflicts and utility of Marxist Feminist frames for sex work research, drawing on findings uncovered through in-depth interviews with online sex workers, alongside critical discourse analysis of media and political commentary. It brings the critical perspective of women into digital workerism and gig economy dialogue who, despite their significant presence within online work, have been overlooked. The autonomist Marxist concept of class composition is adopted to unpack the social, technical and political composition of this often-invisible segment of the service sector. Autonomism makes visible the perspective of workers engaged in processes of mobilization and demobilizaiton. This allows researchers to find everyday forms of resistance which occur within and outside trade unions. On the other hand, Marxist feminist arguments about invisibility politics can generate unhelpful allegories about sex work as domestic labour within the reproductive sphere. Nick Srnicek’s development of Marx’s notion of infrastructure rents helps theorize experiences of unpaid labour within online sex work. Moreover, debates about anti-work politics can cause conflict among sex workers fighting for the labour movement and those rejecting the capitalist work ethic. This illuminates’ tensions caused by white privilege and differing experiences of sex work. The monopolistic and competitive nature of sex work platforms within platform capitalism, and the vulnerable position of marginalised workers within stigmatized/criminalised markets, complicates anti-work politics further. This paper is situated within the feminist sex wars and the intensely divisive question of whether sex workers are victims of the patriarchy or symbols of feminist resistance. Camgirls are shown to engage in radical tactics of resistance against their technical composition on popular sex work platforms. They also engage in creative acts of resistance through performance art, in an attempt to draw attention to stigma and anti-criminalization politics. This sector offers a fascinating window onto grassroots class-action, alongside education about ‘whorephobia.’ A case study of resistance against Only Fans, and a small workers co-operative which emerged during the pandemic, showcases how workers engage in socialist and political acts without the aid of unions. Workers are victims of neoliberalism and simultaneous adopters of neoliberal strategies of survival. The complex dynamics within unions are explored, including tensions with grass-roots resistance, financial pressures and intersecting complications of class, gender and race.

Keywords: autonomist marxism, digital labor, feminism, neoliberalism, sex work, platform capitalism

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Authors: Soroosh Torabi, Brad Berron, Ren Xu, Christine Trinkle

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Microfluidics integrated with 3D cell culture is a powerful technology to mimic cellular environment, and can be used to study cell activities such as proliferation, migration and response to drugs. This technology has gained more attention in cancer studies over the past years, and many organ-on-a-chip systems have been developed to study cancer cell behaviors in an ex-vivo tumor microenvironment. However, there are still some barriers to adoption which include low throughput, complexity in 3D cell culture integration and limitations on non-optical analysis of cells. In this study, a user-friendly microfluidic multi-well plate was developed to mimic the in vivo tumor microenvironment. The microfluidic platform feeds multiple 3D cell culture sites at the same time which enhances the throughput of the system. The platform uses hydrophobic Cassie-Baxter surfaces created by microchannels to enable convenient loading of hydrogel/cell suspensions into the device, while providing barrier free placement of the hydrogel and cells adjacent to the fluidic path. The microchannels support convective flow and diffusion of nutrients to the cells and a removable lid is used to enable further chemical and physiological analysis on the cells. Different breast cancer cell lines were cultured in the device and then monitored to characterize nutrient delivery to the cells as well as cell invasion and proliferation. In addition, the drug response of breast cancer cell lines cultured in the device was compared to the response in xenograft models to the same drugs to analyze relevance of this platform for use in future drug-response studies.

Keywords: microfluidics, multi-well 3d cell culture, tumor microenvironment, tumor-on-a-chip

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Authors: Tadele Araya, Tsehaye Asmelash, Girmatsion Fiseha

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Background: Hepatitis B virus (HBV), Hepatitis C virus (HCV) and Human Immunodeficiency Virus (HIV) constitute serious healthcare problems worldwide. Blood-borne pathogens HBV, HCV and HIV are commonly associated with infections among substance or Injection Drug Users (IDUs). The objective of this study was to determine the prevalence of HBV, HCV, and HIV infections among substance users in Mekelle Substance users Treatment and Rehabilitation Centers. Methods: A cross-sectional study design was used from Dec 2020 to Sep / 2021 to conduct the study. A total of 600 substance users were included. Data regarding the socio-demographic, clinical and sexual behaviors of the substance users were collected using a structured questionnaire. For laboratory analysis, 5-10 ml of venous blood was taken from the substance users. The laboratory analysis was performed by Enzyme-Linked Immunosorbent Assay (ELISA) at Mekelle University, Department of Medical Microbiology and Immunology Research Laboratory. The Data was analyzed using SPSS and Epi-data. The association of variables with HBV, HCV and HIV infections was determined using multivariate analysis and a P value < 0.05 was considered statistically significant. Result: The overall prevalence rate of HBV, HCV and HIV infections were 10%, 6.6%, and 7.5%, respectively. The mean age of the study participants was 28.12 ± 6.9. A higher prevalence of HBV infection was seen in participants who were users of drug injections and in those who were infected with HIV. HCV was comparatively higher in those who had a previous history of unsafe surgical procedures than their counterparts. Homeless participants were highly exposed to HCV and HIV infections than their counterparts. The HBV/HIV Co-infection prevalence was 3.5%. Those doing unprotected sexual practices [P= 0.03], Injection Drug users [P= 0.03], those who had an HBV-infected person in their family [P=0.02], infected with HIV [P= 0.025] were statistically associated with HBV infection. HCV was significantly associated with Substance users and previous history of unsafe surgical procedures [p=0.03, p=0.04), respectively. HIV was significantly associated with unprotected sexual practices and being homeless [p=0.045, p=0.05) respectively. Conclusion-The highly prevalent viral infection was HBV compared to others. There was a High prevalence of HBV/HIV co-infection. The presence of HBV-infected persons in a family, unprotected sexual practices and sharing of needles for drug injection were the risk factors associated with HBV, HIV, and HCV. Continuous health education and screening of the viral infection coupled with medical and psychological treatment is mandatory for the prevention and control of the infections.

Keywords: hepatitis b virus, hepatitis c virus, HIV, substance users

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Authors: Antônio P. de Araújo Neto, Ruy D. A. da Silva Neto, Juliana R. de Souza, Salete K. P. de Medeiros, João T. N. de Medeiros

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The tribological test with Pin-On-Disc configuration measures friction and wear properties in dry or lubricated sliding surfaces of a variety of materials and coatings. Polymeric matrix composites loaded with mineral filler were used, 1%, 3%, 10%, 30%, and 50% mass percentage of filler, to reduce the material cost by using mineral tailings. Using a pin-on-disc tribometer to quantify coefficient of friction and wear resistance of the specimens. The parameters known to performing the test were 300 rpm rotation, normal load of 16N and duration of 33.5 minutes. The composite with 10% mineral filler performed better, considering that the wear resistance was good when compared to the other compositions and an average low coefficient of friction, in the order of μ ≤ 0.15.

Keywords: microcomposites, microparticles tailings of scheelite, PTFE, tribology

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Authors: Yantao Li, Jun Zheng

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Food poison caused by consumption of contaminated food, especially seafood, is one of most serious public health threats worldwide. Vibrio parahaemolyticus is emerging bacterial pathogen and the leading cause of human gastroenteritis associated with food poison, especially in the southern coastal region of China. To successfully cause disease in host, bacterial pathogens need to overcome the host-derived stresses encountered during infection. One of the toxic chemical species elaborated by the host is nitric oxide (NO). NO is generated by acidified nitrite in the stomach and by enzymes of the inducible NO synthase (iNOS) in the host cell, and is toxic to bacteria. Bacterial pathogens have evolved some mechanisms to battle with this toxic stress. Such mechanisms include genes to sense NO produced from immune system and activate others to detoxify NO toxicity, and genes to repair the damage caused by toxic reactive nitrogen species (RNS) generated during NO toxic stress. However, little is known about the NO resistance in V. parahaemolyticus. In this study, a transposon coupled with next generation sequencing (Tn-seq) technology will be utilized to identify genes for NO resistance in V. parahaemolyticus. Our strategy will include construction the saturating transposon insertion library, transposon library challenging with NO, next generation sequencing (NGS), bioinformatics analysis and verification of the identified genes in vitro and in vivo.

Keywords: vibrio parahaemolyticus, nitric oxide, tn-seq, virulence

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Authors: Seyed Abbas Tabatabaei, Afshin Ghanbarzadeh, Mehdi Abidizadeh

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Nowadays the subject of road traffic accidents and the high social and economic costs due to them is the most fundamental problem that experts and providers of transport and traffic brought to a challenge. One of the most effective measures is to enhance the skid resistance of road surface. This research aims to study the intersection of one case in Ahwaz and the effect of increasing the skid resistance in reducing pedestrian injuries in accidents at intersections. In this research the device was developed to measure the coefficient of friction and tried the rules and practices of it have a high similarity with the Locked Wheel Trailer. This device includes a steel frame, wheels, hydration systems, and force gauge. The output of the device is that the force gauge registers. By investigate this data and applying the relationships relative surface coefficient of friction is obtained. Friction coefficient data for the current state and the state of the new pavement are obtained and plotted on the graphs based on the graphs we can compare the two situations and speed at the moment of collision between the two modes are compared. The results show that increasing the coefficient of friction to what extent can be effective on the severity and number of accidents.

Keywords: intersection, coefficient of friction, skid resistance, locked wheels, accident, pedestrian

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Authors: Jae-Chang Kwak, Yong-Seo Koo

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The high efficiency power management IC (PMIC) with switching device is presented in this paper. PMIC is controlled with PFM control method in order to have high power efficiency at high current level. Dynamic Threshold voltage CMOS (DT-CMOS) with low on-resistance is designed to decrease conduction loss. The threshold voltage of DT-CMOS drops as the gate voltage increase, resulting in a much higher current handling capability than standard MOSFET. PFM control circuits consist of a generator, AND gate and comparator. The generator is made to have 1.2MHz oscillation voltage. The DC-DC converter based on PFM control circuit and low on-resistance switching device is presented in this paper.

Keywords: DT-CMOS, PMIC, PFM, DC-DC converter

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Authors: Yaowaporn Sangsen, Kittisak Likhitwitayawuid, Boonchoo Sritularak, Kamonthip Wiwattanawongsa, Ruedeekorn Wiwattanapatapee

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Novel solid lipid nanoparticles (SLNs) were developed to improve oral bioavailability of oxyresveratrol (OXY). The SLNs were prepared by a high speed homogenization technique, at an effective speed and time, using Compritol® 888 ATO (5% w/w) as the solid lipid. The appropriate weight proportions (0.3% w/w) of OXY affected the physicochemical properties of blank SLNs. The effects of surfactant types on the properties of the formulations such as particle size and entrapment efficacy were also investigated. Conclusively, Tween 80 combined with soy lecithin was the most appropriate surfactant to stabilize OXY-loaded SLNs. The mean particle size of the optimized formulation was 134.40 ± 0.57 nm. In vitro drug release study, the selected S2 formulation showed a retarded release profile for OXY with no initial burst release compared to OXY suspension in the simulated gastrointestinal fluids. Therefore, these SLNs could provide a suitable system to develop for the oral OXY delivery.

Keywords: solid lipid nanoparticles, physicochemical properties, in vitro drug release, oxyresveratrol

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Authors: Christian Gaigl, Martin Mensinger

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Once a fire resistance rating is necessary, it has to be proofed that the load bearing behavior of a steel construction under the exposure of fire still fits the static demands. High costs of passive fire protection, which satisfies the requirements, frequently result in a concrete solution. To optimize these expenses, one method is to determine the critical temperature according to the Eurocode DIN EN 1993-1-2. For this purpose, positive effects of hot-dip galvanized surface layers on the temperature development of steel members in the accidental situation of fire exposure has been investigated. The test results show a significant better heating behavior of hot-dip galvanized steel components compared to normal steel specimen. This leads in many cases to a R30 (30 minutes of ISO-fire) fire protection requirement of unprotected steel members and therefore to an economic added value.

Keywords: fire resistance, hot-dip galvanizing, steel constructions, R30 requirement, emissivity

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Authors: Asma Salman, Brian Gabbitas, Peng Cao, Deliang Zhang

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The performance of a coating is strongly dependent upon its microstructure, which in turn is dependent on the characteristics of the feedstock powder. This study involves the evaluation and performance of a titanium-based composite coating produced by the HVOF (high-velocity oxygen fuel) spraying method. The feedstock for making the composite coating was produced using high energy mechanical milling of TiO2 and Al powders followed by a combustion reaction. The characteristics of the feedstock powder were improved by treating it with an organic binder. Two types of coatings were produced using treated and untreated feedstock powders. The microstructures and characteristics of both types of coatings were studied, and their thermal shock resistance was accessed by dipping into molten aluminum. The results of this study showed that feedstock treatment did not have a significant effect on the microstructure of the coatings. However, it did affect the uniformity, thickness and surface roughness of the coating on the steel substrate. A coating produced by an untreated feedstock showed better thermal shock resistance in molten aluminum compared with the one produced by PVA (polyvinyl alcohol) treatment.

Keywords: coating, feedstock, powder processing, thermal shock resistance, thermally spraying

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Authors: Chrysavgi Papagianni

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The tension between global and local has been a usual topic in discussions regarding globalization. Instead of reproducing the usual ‘gloom and doom’ arguments surrounding many of these discussions, the present paper will focus on Emirati film production and more particularly on the work of the acclaimed director Nojoom Alghanem, in order to highlight how local culture can, in fact, become a force of resistance, or else a medium of localization. As a matter of fact, Alghanem’s films, especially Sounds of the Sea, Hamama and Nearby Sky are apt examples of a localizing force in action as they tap into the audience’s dormant memories of the pre-oil past, in a country that has been swept by unprecedented development and globalization in the last 60 years. What becomes evident is that the remediation of memories in Alghanem’s films makes them more ‘mobile’ and thus allows them to circulate better in today’s network society.

Keywords: culture, film, globalization, identity

Procedia PDF Downloads 279