Search results for: receptor diffusion

Authors: Ripon Sarkar, Kabita Chaterjee, Ananya Barui

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Smoking is one of the leading causes of oral cancer. Cigarette smoke affects various cellular parameters and alters molecular metabolism of cells. Epithelial cells losses their cytoskeleton structure, membrane integrity, cellular polarity that subsequently initiates the process of epithelial cells to mesenchymal transition due to long exposure of cigarette smoking. It changes the normal cellular metabolic activity which induces oxidative stress and enhances the reactive oxygen spices (ROS) formation. Excessive ROS and associated oxidative stress are considered to be a driving force in alteration in cellular phenotypes, polarity distribution and mitochondrial metabolism. Noninvasive assessment of such parameters plays essential role in development of routine screening system for early diagnosis of oral cancer. Electrical cell-substrate impedance sensing (ECIS) is one of such method applied for detection of cellular membrane impedance which can be correlated to cell membrane integrity. Present study intends to explore the alteration in cellular impedance along with the expression of cellular polarity molecules and cytoskeleton distributions in oral epithelial cells of habitual smokers and to correlate the outcome to that of clinically diagnosed oral leukoplakia and oral squamous cell carcinoma patients. Total 80 subjects were categorized into four study groups: nonsmoker (NS), cigarette smoker (CS), oral leukoplakia (OLPK) and oral squamous cell carcinoma (OSCC). Cytoskeleton distribution was analyzed by staining of actin filament and generation of ROS was measured using assay kit using standard protocol. Cell impedance was measured through ECIS method at different frequencies. Expression of E-cadherin and protease-activated receptor (PAR) proteins were observed through immune-fluorescence method. Distribution of actin filament is well organized in NS group however; distribution pattern was grossly varied in CS, OLPK and OSCC. Generation of ROS was low in NS which subsequently increased towards OSCC. Expressions of E-cadherin and change in cellular electrical impedance in different study groups indicated the hallmark of cancer progression from NS to OSCC. Expressions of E-cadherin, PAR protein, and cell impedance were decreased from NS to CS and farther OSCC. Generally, the oral epithelial cells exhibit apico-basal polarity however with cancer progression these cells lose their characteristic polarity distribution. In this study expression of polarity molecule and ECIS observation indicates such altered pattern of polarity among smoker group. Overall the present study monitored the alterations in intracellular ROS generation and cell metabolic function, membrane integrity in oral epithelial cells in cigarette smokers. Present study thus has clinical significance, and it may help in developing a noninvasive technique for early diagnosis of oral cancer amongst susceptible individuals.

Keywords: cigarette smoking, early oral cancer detection, electric cell-substrate impedance sensing, noninvasive screening

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Authors: Recep Kesli, Gulşah Asik, Cengiz Demir, Onur Turkyilmaz

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Objective: Acinetobacter baumannii (A. baumannii) can cause health-care associated infections, such as bacteremia, urinary tract and wound infections, endocarditis, meningitis, and pneumonia, particularly in intensive care unit patients. In this study, we aimed to evaluate A. baumannii production in sputum and bronchoalveolar lavage and susceptibilities for antibiotics in a 24 months period. Methods: Between October 2013 and September 2015, Acinetobacter baumannii isolated from respiratory tract speciments were evaluated retrospectively. The strains were isolated from the different intensive care units patients. A. baumannii strains were identified by both the conventional methods and aoutomated identification system -VITEK 2 (bio-Merieux, Marcy l’etoile, France). Antibiotic resistance testing was performed by Kirby-Bauer disc diffusion method according to CLSI criteria. Results: All the ninety isolates included in the study were from respiratory tract specimens. While of all the isolated 90 Acinetobacter baumannii strains were found to be resistant (100%), against ceftriaxone, ceftazidime, ciprofloxacin and piperacillin/ tazobactam, resistance rates against other tested antibiotics found as follows; meropenem 77, 86%, imipenem 75, 83%, trimethoprim-sulfamethoxazole (TMP-STX) 69, 76,6%, gentamicin 51, 56,6% and amikacin 48, 53,3%. Colistin was found as the most effective antibiotic against Acinetobacter baumannii, and there were not found any resistant (0%) strain against colistin. Conclusion: This study demonstrated that the no resistance was found in Acinetobacter baumannii against to colistin. High rates of resistance to carbapenems (imipenem and meropenem) and other tested antibiotics (ceftiaxone, ceftazidime, ciprofloxacine, piperacilline-tazobactam, TMP-STX gentamicin and amikacin) also have remarkable resistance rates. There was a significant relationship between demographic features of patients such as age, undergoing mechanical ventilation, length of hospital stay with resistance rates. High resistance rates against antibiotics require implementation of the infection control program and rational use of antibiotics. In the present study, while there were not found colistin resistance, panresistance were found against to ceftriaxone, ceftazidime, ciprofloxacin and piperacillin/ tazobactam.

Keywords: acinetobacter baumannii, antibiotic resistance, multi drug resistance, intensive care unit

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Authors: Ariel Vilchez, Francisca Acevedo, Rodrigo Navia

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The wound healing process can be accelerated and improved by the action of antioxidants such as curcumin (Cur) over the tissues; however, the efficacy of curcumin used through the digestive system is not enough to exploit its benefits. Electrospinning presents an alternative to carry curcumin directly to the wounds, and polyhydroxybutyrate (PHB) is proposed as the matrix to load curcumin owing to its biodegradable and biocompatible properties. PHB is among 150 types of Polyhydroxyalkanoates (PHAs) identified, it is a natural thermoplastic polyester produced by microbial fermentation obtained from microorganisms. The proposed objective is to develop electrospun bacterial PHB-based microfibers containing curcumin for possible biomedical applications. Commercial PHB was solved in Chloroform: Dimethylformamide (4:1) to a final concentration of 7% m/V. Curcumin was added to the polymeric solution at 1%, and 7% m/m regarding PHB. The electrospinning equipment (NEU-BM, China) with a rotary collector was used to obtain Cur-PHB fibers at different voltages and flow rate of the polymeric solution considering a distance of 20 cm from the needle to the collector. Scanning electron microscopy (SEM) was used to determine the diameter and morphology of the obtained fibers. Thermal stability was obtained from Thermogravimetric (TGA) analysis, and Fourier Transform Infrared Spectroscopy (FT-IR) was carried out in order to study the chemical bonds and interactions. A preliminary curcumin release to Phosphate Buffer Saline (PBS) pH = 7.4 was obtained in vitro and measured by spectrophotometry. PHB fibers presented an intact chemical composition regarding the original condition (dust) according to FTIR spectra, the diameter fluctuates between 0.761 ± 0.123 and 2.157 ± 0.882 μm, with different qualities according to their morphology. The best fibers in terms of quality and diameter resulted in sample 2 and sample 6, obtained at 0-10kV and 0.5 mL/hr, and 0-10kV and 1.5 mL/hr, respectively. The melting temperature resulted near 178 °C, according to the bibliography. The crystallinity of fibers decreases while curcumin concentration increases for the studied interval. The curcumin release reaches near 14% at 37 °C at 54h in PBS adjusted to a quasi-Fickian Diffusion. We conclude that it is possible to load curcumin in PHB to obtain continuous, homogeneous, and solvent-free microfibers by electrospinning. Between 0% and 7% of curcumin, the crystallinity of fibers decreases as the concentration of curcumin increases. Thus, curcumin enhances the flexibility of the obtained material. HPLC should be used in further analysis of curcumin release.

Keywords: antioxidant, curcumin, polyhydroxybutyrate, wound healing

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Authors: Hammad Majeed, Hanna Knuutila, Magne Hillestad, Hallvard F. Svendsen

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Formation of aerosols can cause serious complications in industrial exhaust gas CO2 capture processes. SO3 present in the flue gas can cause aerosol formation in an absorption based capture process. Small mist droplets and fog formed can normally not be removed in conventional demisting equipment because their submicron size allows the particles or droplets to follow the gas flow. As a consequence of this aerosol based emissions in the order of grams per Nm3 have been identified from PCCC plants. In absorption processes aerosols are generated by spontaneous condensation or desublimation processes in supersaturated gas phases. Undesired aerosol development may lead to amine emissions many times larger than what would be encountered in a mist free gas phase in PCCC development. It is thus of crucial importance to understand the formation and build-up of these aerosols in order to mitigate the problem. Rigorous modelling of aerosol dynamics leads to a system of partial differential equations. In order to understand mechanics of a particle entering an absorber an implementation of the model is created in Matlab. The model predicts the droplet size, the droplet internal variable profiles and the mass transfer fluxes as function of position in the absorber. The Matlab model is based on a subclass method of weighted residuals for boundary value problems named, orthogonal collocation method. The model comprises a set of mass transfer equations for transferring components and the essential diffusion reaction equations to describe the droplet internal profiles for all relevant constituents. Also included is heat transfer across the interface and inside the droplet. This paper presents results describing the basic simulation tool for the characterization of aerosols formed in CO2 absorption columns and gives examples as to how various entering droplets grow or shrink through an absorber and how their composition changes with respect to time. Below are given some preliminary simulation results for an aerosol droplet composition and temperature profiles.

Keywords: absorption columns, aerosol formation, amine emissions, internal droplet profiles, monoethanolamine (MEA), post combustion CO2 capture, simulation

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Authors: Joan Edwards, J. Lawlor

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Technological innovation is frequently defined in terms of bringing a new invention to market through a relatively straightforward process of diffusion. In reality, this process is complex and non-linear in nature, and includes social and cognitive factors that influence the development of an emerging technology and its related market or environment. As recent studies contend technological trajectory is part of technological paradigms, which arise from the expectations and desires of industry agents and results in co-evolution, it may be realised that social factors play a major role in the development of a technology. It is conjectured that collective social behaviour is fuelled by individual motivations and expectations, which inform the possibilities and uses for a new technology. The individual outlook highlights the issues present at the micro-level of developing a technology. Accordingly, this may be zoomed out to realise how these embedded social structures, influence activities and expectations at a macro level and can ultimately strategically shape the development and use of a technology. These social factors rely on communication to foster the innovation process. As innovation may be defined as the implementation of inventions, technological change results from the complex interactions and feedback occurring within an extended environment. The framework presented in this paper, recognises that social mechanisms provide the basis for an iterative dialogue between an innovator, a new technology, and an environment - within which social and cognitive ‘identity-shaping’ elements of the innovation process occur. Identity-shaping characteristics indicate that an emerging technology has a performative nature that transforms, alters, and ultimately configures the environment to which it joins. This identity–shaping quality is termed as ‘performative’. This paper examines how technologies evolve within a socio-technological sphere and how 'performativity' facilitates the process. A framework is proposed that incorporates the performative elements which are identified as feedback, iteration, routine, expectations, and motivations. Additionally, the concept of affordances is employed to determine how the role of the innovator and technology change over time - constituting a more conducive environment for successful innovation.

Keywords: affordances, framework, performativity, strategic innovation

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Authors: Huang Hao, Li Weiwen

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Global biodiversity continues to decline as a result of global climate change and various human activities, such as habitat destruction, pollution, introduction of alien species and overfishing. Although there are connections between global marine organisms more or less, it is better to have clear geographical boundaries in order to facilitate the assessment and management of different biogeographical zones. And so area based management tools (ABMT) are considered as the most effective means for the conservation and sustainable use of marine biodiversity. On a large scale, the geographical gap (or barrier) is the main factor to influence the connectivity, diffusion, ecological and evolutionary process of marine organisms, which results in different distribution patterns. On a small scale, these factors include geographical location, geology, and geomorphology, water depth, current, temperature, salinity, etc. Therefore, the analysis on geographic and environmental factors is of great significance in the study of biodiversity characteristics. This paper summarizes the marine spatial classification and ABMTs used in coastal area, open oceans and deep sea. And analysis principles and methods of marine spatial classification based on biogeographic related factors, and take China Near Sea (CNS) area as case study, and select key biogeographic related factors, carry out marine spatial classification at biological region scale, ecological regionals scale and biogeographical scale. The research shows that CNS is divided into 5 biological regions by climate and geographical differences, the Yellow Sea, the Bohai Sea, the East China Sea, the Taiwan Straits, and the South China Sea. And the bioregions are then divided into 12 ecological regions according to the typical ecological and administrative factors, and finally the eco-regions are divided into 98 biogeographical units according to the benthic substrate types, depth, coastal types, water temperature, and salinity, given the integrity of biological and ecological process, the area of the biogeographical units is not less than 1,000 km². This research is of great use to the coastal management and biodiversity conservation for local and central government, and provide important scientific support for future spatial planning and management of coastal waters and sustainable use of marine biodiversity.

Keywords: spatial classification, marine biodiversity, bio-geographical, conservation

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Authors: Md. Samsuddin Ansari, Ashish Arora

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Every year 10 million people fall ill with one of the oldest diseases known as tuberculosis, caused by Mycobacterium tuberculosis. The success of M. tuberculosis as a pathogen is because of its ability to persist in host tissues. Multidrug resistance (MDR) mycobacteria cases increase every day, which is associated with efflux pumps controlled at the level of transcription. The transcription regulators of MDR transporters in bacteria belong to one of the following four regulatory protein families: AraC, MarR, MerR, and TetR. Phenolic acid decarboxylase repressor (PadR), like a family of transcription regulators, is closely related to the MarR family. Phenolic acid decarboxylase repressor (PadR) was first identified as a transcription factor involved in the regulation of phenolic acid stress response in various microorganisms (including Mycobacterium tuberculosis H37Rv). Recently research has shown that the PadR family transcription factors are global, multifunction transcription regulators. Rv0047c is a PadR subfamily-1 protein. We are exploring the biophysical and structural characterization of Rv0047c. The Rv0047 gene was amplified by PCR using the primers containing EcoRI and HindIII restriction enzyme sites cloned in pET-NH6 vector and overexpressed in DH5α and BL21 (λDE3) cells of E. coli following purification with Ni2+-NTA column and size exclusion chromatography. We did DSC to know the thermal stability; the Tm (transition temperature) of protein is 55.29ºC, and ΔH (enthalpy change) of 6.92 kcal/mol. Circular dichroism to know the secondary structure and conformation and fluorescence spectroscopy for tertiary structure study of protein. To understand the effect of pH on the structure, function, and stability of Rv0047c we employed spectroscopy techniques such as circular dichroism, fluorescence, and absorbance measurements in a wide range of pH (from pH-2.0 to pH-12). At low and high pH, it shows drastic changes in the secondary and tertiary structure of the protein. EMSA studies showed the specific binding of Rv0047c with its own 30-bp promoter region. To determine the effect of complex formation on the secondary structure of Rv0047c, we examined the CD spectra of the complex of Rv0047c with promoter DNA of rv0047. The functional role of Rv0047c was characterized by over-expressing the Rv0047c gene under the control of hsp60 promoter in Mycobacterium tuberculosis H37Rv. We have predicted the three-dimensional structure of Rv0047c using the Swiss Model and Modeller, with validity checked by the Ramachandra plot. We did molecular docking of Rv0047c with dnaA, through PatchDock following refinement through FireDock. Through this, it is possible to easily identify the binding hot-stop of the receptor molecule with that of the ligand, the nature of the interface itself, and the conformational change undergone by the protein pattern. We are using X-crystallography to unravel the structure of Rv0047c. Overall the studies show that Rv0047c may have transcription regulation along with providing an insight into the activity of Rv0047c in the pH range of subcellular environment and helps to understand the protein-protein interaction, a novel target to kill dormant bacteria and potential strategy for tuberculosis control.

Keywords: mycobacterium tuberculosis, phenolic acid decarboxylase repressor, Rv0047c, Circular dichroism, fluorescence spectroscopy, docking, protein-protein interaction

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Authors: Saeidreza Radpour, Md. Ahiduzzaman, Amit Kumar

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Alberta’s mining sector consumed 871.3 PJ in 2012, which is 67.1% of the energy consumed in the industry sector and about 40% of all the energy consumed in the province of Alberta. Natural gas, petroleum products, and electricity supplied 55.9%, 20.8%, and 7.7%, respectively, of the total energy use in this sector. Oil sands mining and upgrading to crude oil make up most of the mining energy sector activities in Alberta. Crude oil is produced from the oil sands either by in situ methods or by the mining and extraction of bitumen from oil sands ore. In this research, the factors affecting oil sands production have been assessed and a framework has been developed for market penetration of new efficient technologies in this sector. Oil sands production amount is a complex function of many different factors, broadly categorized into technical, economic, political, and global clusters. The results of developed and implemented statistical analysis in this research show that the importance of key factors affecting on oil sands production in Alberta is ranked as: Global energy consumption (94% consistency), Global crude oil price (86% consistency), and Crude oil export (80% consistency). A framework for modeling oil sands energy technologies’ market penetration (OSETMP) has been developed to cover related technical, economic and environmental factors in this sector. It has been assumed that the impact of political and social constraints is reflected in the model by changes of global oil price or crude oil price in Canada. The market share of novel in situ mining technologies with low energy and water use are assessed and calculated in the market penetration framework include: 1) Partial upgrading, 2) Liquid addition to steam to enhance recovery (LASER), 3) Solvent-assisted process (SAP), also called solvent-cyclic steam-assisted gravity drainage (SC-SAGD), 4) Cyclic solvent, 5) Heated solvent, 6) Wedge well, 7) Enhanced modified steam and Gas push (emsagp), 8) Electro-thermal dynamic stripping process (ET-DSP), 9) Harris electro-magnetic heating applications (EMHA), 10) Paraffin froth separation. The results of the study will show the penetration profile of these technologies over a long term planning horizon.

Keywords: appliances efficiency improvement, diffusion models, market penetration, residential sector

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Authors: Parul Kulshreshtha, Subrata Sinha, Rakesh Bhatnagar

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This study was conducted by taking B. anthracis as a model pathogen. On infecting a host, B. anthracis secretes three proteins, namely, protective antigen (PA, 83kDa), edema factor (EF, 89 kDa) and lethal factor (LF, 90 kDa). These three proteins are the components of two anthrax toxins. PA binds to the cell surface receptors, namely, tumor endothelial marker (TEM) 8 and capillary morphogenesis protein (CMG) 2. TEM8 and CMG2 interact with LDL-receptor related protein (LRP) 6 for endocytosis of EF and LF. On entering the cell, EF acts as a calmodulin-dependent adenylate cyclase that causes a prolonged increase of cytosolic cyclic adenosine monophosphate (cAMP). LF is a metalloprotease that cleaves most isoforms of mitogen-activated protein kinase kinases (MAPKK/MEK) close to their N-terminus. By secreting these two toxins, B.anthracis ascertains death of the host. Once the systemic levels of the toxins rise, antibiotics alone cannot save the host. Therefore, toxin-specific inhibitors have to be developed. In this wake, monoclonal antibodies have been developed for the neutralization of toxic effects of anthrax toxins. We created hybridomas by using spleen of mice that were actively immunized with rLFn (recombinant N-terminal domain of lethal factor of B. anthracis) to obtain anti-toxin antibodies. Later on, separate group of mice were immunized with rLFn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. This led to the identification of one cohort of rLFn-immunized mice that harboured disease-enhancing polyclonal antibodies. At the same time, the monoclonal antibodies from all the hybridomas were being tested. Two hybridomas secreted monoclonal antibodies (H8 and H10) that were cross-reactive with EF (edema factor) and LF (lethal factor), while the other two hybridomas secreted LF-specific antibodies (H7 and H11). The protective efficacy of H7, H8, H10 and H11 was investigated. H7, H8 and H10 were found to be protective. H11 was found to have disease enhancing characteristics in-vitro and in mouse model of challenge with B. anthracis. In this study the disease enhancing character of H11 monoclonal antibody and anti-rLFn polyclonal sera was investigated. Combination of H11 with protective monoclonal antibodies (H8 and H10) reduced its disease enhancing nature both in-vitro and in-vivo. But combination of H11 with LETscFv (an scFv with VH and VL identical to H10 but lacking Fc region) could not abrogate the disease-enhancing character of H11 mAb. Therefore it was concluded that for suppression of disease enhancement, Fc portion was absolutely essential for interaction of H10 with H11. Our study indicates that the protective potential of an antibody depends equally on its idiotype/ antigen specificity and its isotype. A number of monoclonal and engineered antibodies are being explored as immunotherapeutics but it is absolutely essential to characterize each one for their individual and combined protective potential. Although new in the sphere of toxin-based diseases, it is extremely important to characterize the disease-enhancing nature of polyclonal as well as monoclonal antibodies. This is because several anti-viral therapeutics and vaccines have failed in the face of this phenomenon. The passive –immunotherapy thus needs to be well formulated to avoid any contraindications.

Keywords: immunotherapy, polyclonal, monoclonal, antibody-dependent disease enhancement

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Authors: B. Atika, S. Lehmann, E. Wimmer

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The defense strategy is very common in the insect world. Defensive substances play a wide variety of functions for beetles, such as repellents, toxicants, insecticides, and antimicrobics. Beetles react to predators, invaders, and parasitic microbes with the release of toxic and repellent substances. Defensive substances are directed against a large array of potential target organisms or may function for boiling bombardment or as surfactants. Usually, Coleoptera biosynthesize and store their defensive compounds in a complex secretory organ, known as odoriferous defensive stink glands. The red flour beetle, Tribolium castaneum (Coleoptera: Tenebrionidae), uses these glands to produce antimicrobial p-benzoquinones and 1-alkenes. In the past, the morphology of stink gland has been studied in detail in tenebrionid beetles; however, very little is known about the genes that are involved in the production of gland secretion. In this study, we studied a subset of genes that are essential for the benzoquinone production in red flour beetle. In the first phase, we selected 74 potential candidate genes from a genome-wide RNA interference (RNAi) knockdown screen named 'iBeetle.' All these 74 candidate genes were functionally characterized by RNAi-mediated gene knockdown. Therefore, they were selected for a subsequent gas chromatography-mass spectrometry (GC-MS) analysis of secretion volatiles in respective RNAi knockdown glands. 33 of them were observed to alter the phenotype of stink gland. In the GC-MS analysis, 7 candidate genes were noted to display a strongly altered gland, in terms of secretion color and chemical composition, upon knockdown, showing their key role in the biosynthesis of gland secretion. Morphologically altered stink glands were found for odorant receptor and protein kinase superfamily. Subsequent GC-MS analysis of secretion volatiles revealed reduced benzoquinone levels in LIM domain, PDZ domain, PBP/GOBP family knockdowns and a complete lack of benzoquinones in the knockdown of sulfatase-modifying factor enzyme 1, sulfate transporter family. Based on stink gland transcriptome data, we analyzed the function of sulfatase-modifying factor enzyme 1 and sulfate transporter family via RNAi-mediated gene knockdowns, GC-MS, in situ hybridization, and enzymatic activity assays. Morphologically altered stink glands were noted in knockdown of both these genes. Furthermore, GC-MS analysis of secretion volatiles showed a complete lack of benzoquinones in the knockdown of these two genes. In situ hybridization showed that these two genes are expressed around the vesicle of certain subgroup of secretory stink gland cells. Enzymatic activity assays on stink gland tissue showed that these genes are involved in p-benzoquinone biosynthesis. These results suggest that sulfatase-modifying factor enzyme 1 and sulfate transporter family play a role specifically in benzoquinone biosynthesis in red flour beetles.

Keywords: Red Flour Beetle, defensive stink gland, benzoquinones, sulfate transporter, sulfatase-modifying factor enzyme 1

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Authors: Kei Kamada, Rikito Murakami, Masahiko Ito, Mototaka Arakawa, Yasuhiro Shoji, Toshiyuki Ueno, Masao Yoshino, Akihiro Yamaji, Shunsuke Kurosawa, Yuui Yokota, Yuji Ohashi, Akira Yoshikawa

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Techniques of energy harvesting y have been widely developed in recent years, due to high demand on the power supply for ‘Internet of things’ devices such as wireless sensor nodes. In these applications, conversion technique of mechanical vibration energy into electrical energy using magnetostrictive materials n have been brought to attention. Among the magnetostrictive materials, Fe-Ga and Fe-Al alloys are attractive materials due to the figure of merits such price, mechanical strength, high magnetostrictive constant. Up to now, bulk crystals of these alloys are produced by the Bridgman–Stockbarger method or the Czochralski method. Using these method big bulk crystal up to 2~3 inch diameter can be grown. However, non-uniformity of chemical composition along to the crystal growth direction cannot be avoid, which results in non-uniformity of magnetostriction constant and reduction of the production yield. The micro-pulling down (μ-PD) method has been developed as a shaped crystal growth technique. Our group have reported shaped crystal growth of oxide, fluoride single crystals with different shape such rod, plate tube, thin fiber, etc. Advantages of this method is low segregation due to high growth rate and small diffusion of melt at the solid-liquid interface, and small kerf loss due to near net shape crystal. In this presentation, we report the shaped long plate crystal growth of Fe-Ga and Fe-Al alloys using the μ-PD method. Alloy crystals were grown by the μ-PD method using calcium oxide crucible and induction heating system under the nitrogen atmosphere. The bottom hole of crucibles was 5 x 1mm² size. A <100> oriented iron-based alloy was used as a seed crystal. 5 x 1 x 320 mm³ alloy crystal plates were successfully grown. The results of crystal growth, chemical composition analysis, magnetostrictive properties and a prototype vibration energy harvester are reported. Furthermore, continuous crystal growth using powder supply system will be reported to minimize the chemical composition non-uniformity along the growth direction.

Keywords: crystal growth, micro-pulling-down method, Fe-Ga, Fe-Al

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Authors: Nicholas Mavrogiannis, Francesca Crivellari, Zachary Gagnon

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Development of low-cost, rapid, sensitive and portable biosensing systems are important for the detection and prevention of disease in developing countries, biowarfare/antiterrorism applications, environmental monitoring, point-of-care diagnostic testing and for basic biological research. Currently, the most established commercially available and widespread assays for portable point of care detection and disease testing are paper-based dipstick and lateral flow test strips. These paper-based devices are often small, cheap and simple to operate. The last three decades in particular have seen an emergence in these assays in diagnostic settings for detection of pregnancy, HIV/AIDS, blood glucose, Influenza, urinary protein, cardiovascular disease, respiratory infections and blood chemistries. Such assays are widely available largely because they are inexpensive, lightweight, and portable, are simple to operate, and a few platforms are capable of multiplexed detection for a small number of sample targets. However, there is a critical need for sensitive, quantitative and multiplexed detection capabilities for point-of-care diagnostics and for the detection and prevention of disease in the developing world that cannot be satisfied by current state-of-the-art paper-based assays. For example, applications including the detection of cardiac and cancer biomarkers and biothreat applications require sensitive multiplexed detection of analytes in the nM and pM range, and cannot currently be satisfied with current inexpensive portable platforms due to their lack of sensitivity, quantitative capabilities and often unreliable performance. In this talk, inexpensive label-free biomolecular detection at liquid interfaces using a newly discovered electrokinetic phenomenon known as fluidic dielectrophoresis (fDEP) is demonstrated. The electrokinetic approach involves exploiting the electrical mismatches between two aqueous liquid streams forced to flow side-by-side in a microfluidic T-channel. In this system, one fluid stream is engineered to have a higher conductivity relative to its neighbor which has a higher permittivity. When a “low” frequency (< 1 MHz) alternating current (AC) electrical field is applied normal to this fluidic electrical interface the fluid stream with high conductivity displaces into the low conductive stream. Conversely, when a “high” frequency (20MHz) AC electric field is applied, the high permittivity stream deflects across the microfluidic channel. There is, however, a critical frequency sensitive to the electrical differences between each fluid phase – the fDEP crossover frequency – between these two events where no fluid deflection is observed, and the interface remains fixed when exposed to an external field. To perform biomolecular detection, two streams flow side-by-side in a microfluidic T-channel: one fluid stream with an analyte of choice and an adjacent stream with a specific receptor to the chosen target. The two fluid streams merge and the fDEP crossover frequency is measured at different axial positions down the resulting liquid

Keywords: biodetection, fluidic dielectrophoresis, interfacial polarization, liquid interface

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Authors: Emmanuel Jaluchimike Iloputaife, Kelechi Nkechinyere Mbah-Omeje

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This study was designed to determine the antimicrobial activities and minimum inhibitory concentration of three different batches (Fresh, Oven dried and Sundried) of Ass Hay extracted with water, ethanol and methanolagainst selected human pathogenic microorganisms (Escherichia coli, Klebsiella Pneumonia, Staphylococcus aureus, Aspergillus niger and Candidaalbicans). All extracts were reconstituted with peptone water and tested for antimicrobial activity. The antimicrobial activity, the Minimum Inhibitory Concentration and Minimum Bactericidal/Fungicidal concentrations were determined by agar well diffusion methodagainst test organismsin which aseptic conditions were observed. The antimicrobial activities of the different batches of Ass Hay on the test organisms varied considerably. The highest inhibition zone diameter at 200 mg/ml for the different batches of Ass Hay was recorded by sundried methanol extract against Escherichia coli at 36.4 ± 0.2 mm while fresh methanol extract inhibited Klebsiela pneumonia with the least inhibition zone diameter at 20.1 ± 0.1mm. At 100 mg/ml the highest inhibition zone diameter was recorded by oven dried water extract against Escherichia coli at 30.3 ± 0.3 mm while sun dried water extract inhibited Staphylococcus aureus with the least inhibition zone diameter at 15.1 ± 0.1 mm. At 50mg/ml, the highest inhibition zone diameter was recorded by fresh water extract against Escherichia coli at 25.9 ± 0.1 mm while oven dried water extract inhibited Klebsiela pneumonia with least inhibition zone diameter at 12.1 ± 0.2 mm. At 25mg/ml, the highest inhibition zone diameter was recorded by fresh water extract against Escherichia coli at 18.3 ± 0.2 mm while sun dried ethanol extract inhibited Escherichia coli with least inhibition zone diameter at 10.1 ± 0.1 mm. The MIC and MBC result of ethanol extract of fresh Ass Hay showed a uniform value of 6.25 mg/ml and 12.5 mg/ml respectively for all test bacterial isolates. The Minimum Inhibitory concentration and Minimum bactericidal concentration results of Oven dried ethanol Ass Hay extract showed a uniform value of 3.125 mg/ml and 6.25 mg/ml respectively for all test bacterial isolates and Minimum fungicidal concentration value of 12.5 mg/ml for Aspergillus niger. Statistical analysis showed there is significant difference in mean zone inhibition diameter of the products at p < 0.05, p = 0.019. This study has shown there is antimicrobial potential in Ass Hay and at such there is need to further exploit Donkey Ass Hay in order to maximize the potential.

Keywords: microorganisms, Ass Hay, antimicrobial activity, extracts

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Authors: Emma O’ Keeffe, Helen Hughes, Peter McLoughlin, Shiau Pin Tan, Nick McCarthy

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Biosecurity is emerging as one of the most important issues facing the agricultural and forestry community. This is as a result of increased invasion from new pests and diseases with the main protocol for dealing with these species being the use of synthetic pesticides. However, these chemicals have been shown to exhibit negative effects on the environment. Seaweeds represent a vast untapped resource of bio-molecules with a broad range of biological activities including pesticidal. This project investigated both the antifungal and antibacterial activity of seaweed species against two problematic root rot fungi, Armillaria mellea and Heterobasidion annosum and ten quarantine bacterial plant pathogens including Xanthomonas arboricola, Xanthomonas fragariae, and Erwinia amylovora. Four seaweed species were harvested from the South-East coast of Ireland including brown, red and green varieties. The powdered seaweeds were extracted using four different solvents by liquid extraction. The poisoned food technique was employed to establish the antifungal efficacy, and the standard disc diffusion assay was used to assess the antibacterial properties of the seaweed extracts. It was found that extracts of the green seaweed exhibited antifungal activity against H. annosum, with approximately 50% inhibition compared to the negative control. The protectant activities of the active extracts were evaluated on disks of Picea sitchensis, a plant species sensitive to infection from H. annosum and compared to the standard chemical control product urea. The crude extracts exhibited very similar activity to the 10% and 20% w/v concentrations of urea, demonstrating the ability of seaweed extracts to compete with commercially available products. Antibacterial activity was exhibited by a number of seaweed extracts with the red seaweed illustrating the strongest activity, with a zone of inhibition of 15.83 ± 0.41 mm exhibited against X. arboricola whilst the positive control (10 μg/disk of chloramphenicol) had a zone of 26.5 ± 0.71 mm. These results highlight the potential application of seaweed extracts in the forestry and agricultural industries for use as biopesticides. Further work is now required to identify the bioactive molecules that are responsible for this antifungal and antibacterial activity in the seaweed extracts, including toxicity studies to ensure the extracts are non-toxic to plants and humans.

Keywords: antibacterial, antifungal, biopesticides, seaweeds

Procedia PDF Downloads 173

Authors: Berengere Vire, Nicolas Salvetat, Yoann Lannay, Guillaume Marcellin, Siem Van Der Laan, Franck Molina, Dinah Weissmann

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Predicting suicidal behaviors is one of the most complex challenges of daily psychiatric practices. Today, suicide risk prediction using biological tools is not validated and is only based on subjective clinical reports of the at-risk individual. Therefore, there is a great need to identify biomarkers that would allow early identification of individuals at risk of suicide. Alterations of adenosine-to-inosine (A-to-I) RNA editing of neurotransmitter receptors and other proteins have been shown to be involved in etiology of different psychiatric disorders and linked to suicidal behavior. RNA editing is a co- or post-transcriptional process leading to a site-specific alteration in RNA sequences. It plays an important role in the epi transcriptomic regulation of RNA metabolism. On postmortem human brain tissue (prefrontal cortex) of depressed suicide victims, Alcediag found specific alterations of RNA editing activity on the mRNA coding for the serotonin 2C receptor (5-HT2cR). Additionally, an increase in expression levels of ADARs, the RNA editing enzymes, and modifications of RNA editing profiles of prime targets, such as phosphodiesterase 8A (PDE8A) mRNA, have also been observed. Interestingly, the PDE8A gene is located on chromosome 15q25.3, a genomic region that has recurrently been associated with the early-onset major depressive disorder (MDD). In the current study, we examined whether modifications in RNA editing profile of prime targets allow identifying disease-relevant blood biomarkers and evaluating suicide risk in patients. To address this question, we performed a clinical study to identify an RNA editing signature in blood of depressed patients with and without the history of suicide attempts. Patient’s samples were drawn in PAXgene tubes and analyzed on Alcediag’s proprietary RNA editing platform using next generation sequencing technology. In addition, gene expression analysis by quantitative PCR was performed. We generated a multivariate algorithm comprising various selected biomarkers to detect patients with a high risk to attempt suicide. We evaluated the diagnostic performance using the relative proportion of PDE8A mRNA editing at different sites and/or isoforms as well as the expression of PDE8A and the ADARs. The significance of these biomarkers for suicidality was evaluated using the area under the receiver-operating characteristic curve (AUC). The generated algorithm comprising the biomarkers was found to have strong diagnostic performances with high specificity and sensitivity. In conclusion, we developed tools to measure disease-specific biomarkers in blood samples of patients for identifying individuals at the greatest risk for future suicide attempts. This technology not only fosters patient management but is also suitable to predict the risk of drug-induced psychiatric side effects such as iatrogenic increase of suicidal ideas/behaviors.

Keywords: blood biomarker, next-generation-sequencing, RNA editing, suicide

Procedia PDF Downloads 259

Authors: Bernice Jeanne Lottering, Yi-Wen Lin

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Introduction: Chronic pain has a definitive lack of objective parameters in the measurement and treatment efficacy of diseases such as Fibromyalgia (FM). Persistent widespread pain and generalized tenderness are the characteristic symptoms affecting a large majority of the global population, particularly females. This disease has indicated a refractory tendency to conventional treatment ventures, largely resultant from a lack of etiological and pathogenic understanding of the disease development. Emerging evidence indicates that the central nervous system (CNS) plays a critical role in the amplification of pain signals and the neurotransmitters associated therewith. Various stimuli have been found to activate the channels existent on nociceptor terminals, thereby actuating nociceptive impulses along the pain pathways. The transient receptor potential vanalloid 1 (TRPV1) channel functions as a molecular integrator for numerous sensory inputs, such as nociception, and was explored in the current study. Current intervention approaches face a multitude challenges, ranging from effective therapeutic interventions to the limitation of pathognomonic criteria resultant from incomplete understanding and partial evidence on the mechanisms of action of FM. It remains unclear whether electroacupuncture (EA) plays an integral role in the functioning of the TRPV1 pathway, and whether or not it can reduce the chronic pain induced by FM. Aims: The aim of this study was to explore the mechanisms underlying the activation and modulation of the TRPV1 channel pathway in a cold stress model of FM applied to a murine model. Furthermore, the effect of EA in the treatment of mechanical and thermal pain, as expressed in FM was also to be investigated. Methods: 18 C57BL/6 wild type and 6 TRPV1 knockout (KO) mice, aged 8-12 weeks, were exposed to an intermittent cold stress-induced fibromyalgia-like pain model, with or without EA treatment at ZusanLi ST36 (2Hz/20min) on day 3 to 5. Von Frey and Hargreaves behaviour tests were implemented in order to analyze the mechanical and thermal pain thresholds on day 0, 3 and 5 in control group (C), FM group (FM), FM mice with EA treated group (FM + EA) and FM in KO group. Results: An increase in mechanical and thermal hyperalgesia was observed in the FM, EA and KO groups when compared to the control group. This initial increase was reduced in the EA group, which directs focus at the treatment efficacy of EA in nociceptive sensitization, and the analgesic effect EA has attenuating FM associated pain. Discussion: An increase in the nociceptive sensitization was observed through higher withdrawal thresholds in the von Frey mechanical test and the Hargreaves thermal test. TRPV1 function in mice has been scientifically associated with these nociceptive conduits, and the increased behaviour test results suggest that TRPV1 upregulation is central to the FM induced hyperalgesia. This data was supported by the decrease in sensitivity observed in results of the TRPV1 KO group. Moreover, the treatment of EA showed a decrease in this FM induced nociceptive sensitization, suggesting TRPV1 upregulation and overexpression can be attenuated by EA at bilateral ST36. This evidence compellingly implies that the analgesic effect of EA is associated with TRPV1 downregulation.

Keywords: fibromyalgia, electroacupuncture, TRPV1, nociception

Procedia PDF Downloads 139

Authors: Chiara Magliacane

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This project aims to analyse the relationship between the post-conflict Northern Irish environment and youth trauma in deprived areas. Using an anthropological perspective and methodology, the study investigates the possible contribution that a socio-cultural perspective can give to the current research on the field, with a special focus on the role of transgenerational trauma. The recognition of the role that socio-economic determinants have on health is usually a challenge for social researchers. In post-conflict Northern Ireland, the overall lack of research about connections between the social context and youth trauma opens the way to the present project. Anthropological studies on social implications of mental disorders have achieved impressive results in many societies; they show how conditions of sufferance and poverty are not intrinsically given, but are the products of historical processes and events. The continuum of violence and the politics of victimhood sustains a culture of silence and fear in deprived areas; this implies the need of investigating the structural and symbolic violence that lies behind the diffusion of mental suffering. The project refers to these concepts from Medical Anthropology and looks at connections between trauma and social, political and economic structures. Accordingly, the study considers factors such as poverty, unemployment, social inequality and gender and class perspectives. At the same time, the project problematises categories such as youth and trauma. 'Trauma' is currently debated within the social sciences since the 'invention' of the Post-Traumatic Stress Disorder (PTSD) in 1980. Current critics made to its clinical conception show how trauma has been mainly analysed as a memory of the past. On the contrary, medical anthropological research focuses on wider perspectives on society and its structures; this is a new and original approach to the study of youth trauma considering that, to author’s best knowledge, there is no research of this kind regarding Northern Ireland. Methods: Qualitative interviews, participant observation. Expected Impact: Local Northern Ireland organizations, i.e. specific charities that provide mental health support. Ongoing and present connections will ensure they will hear about this research.

Keywords: health and social inequalities, Northern Ireland, structural violence, youth

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Authors: Aleksander Ejsmont, Aleksandra Galarda, Joanna Goscianska

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Smart porous carriers with defined structure and physicochemical properties are required for releasing the therapeutic drug with precise control of delivery time and location in the body. Due to their non-toxicity, ordered structure, chemical, and thermal stability, mesoporous carbons can be considered as modern carriers for active pharmaceutical ingredients (APIs) whose effectiveness needs frequent dosing algorithms. Such an API-carrier system, if programmed precisely, may stabilize the pharmaceutical and increase its dissolution leading to enhanced bioavailability. The substance conjugated with the material, through its prior adsorption, can later be successfully applied internally to the organism, as well as externally if the API release is feasible under these conditions. In the present study, ordered mesoporous carbons of different morphologies and structures, prepared by hard template method, were applied as carriers in the adsorption and controlled release of active pharmaceutical ingredients. In the first stage, the carbon materials were synthesized and functionalized with carboxylic groups by chemical oxidation using ammonium persulfate solution and then with amine groups. Materials obtained were thoroughly characterized with respect to morphology (scanning electron microscopy), structure (X-ray diffraction, transmission electron microscopy), characteristic functional groups (FT-IR spectroscopy), acid-base nature of surface groups (Boehm titration), parameters of the porous structure (low-temperature nitrogen adsorption) and thermal stability (TG analysis). This was followed by a series of tests of adsorption and release of paracetamol, benzocaine, and losartan potassium. Drug release experiments were performed in the simulated gastric fluid of pH 1.2 and phosphate buffer of pH 7.2 or 6.8 at 37.0 °C. The XRD patterns in the small-angle range and TEM images revealed that functionalization of mesoporous carbons with carboxylic or amine groups leads to the decreased ordering of their structure. Moreover, the modification caused a considerable reduction of the carbon-specific surface area and pore volume, but it simultaneously resulted in changing their acid-base properties. Mesoporous carbon materials exhibit different morphologies, which affect the host-guest interactions during the adsorption process of active pharmaceutical ingredients. All mesoporous carbons show high adsorption capacity towards drugs. The sorption capacity of materials is mainly affected by BET surface area and the structure/size matching between adsorbent and adsorbate. Selected APIs are linked to the surface of carbon materials mainly by hydrogen bonds, van der Waals forces, and electrostatic interactions. The release behavior of API is highly dependent on the physicochemical properties of mesoporous carbons. The release rate of APIs could be regulated by the introduction of functional groups and by changing the pH of the receptor medium. Acknowledgments—This research was supported by the National Science Centre, Poland (project SONATA-12 no: 2016/23/D/NZ7/01347).

Keywords: ordered mesoporous carbons, sorption capacity, drug delivery, carbon nanocarriers

Procedia PDF Downloads 176

Authors: Ricardo Godoy, Herbert Venthur, Hector Jimenez, Andres Quiroz, Ana Mutis

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In agriculture, grape production has great economic importance at global level, considering that in 2013 it reached 7.4 million hectares (ha) covered by plantations of this fruit worldwide. Chile is the number one exporter in the world with 800,000 tons. However, these values have been threatened by the attack of the grapevine moth, Lobesia botrana (Denis & Schiffermuller) (Lepidoptera: Tortricidae), since its detection in 2008. Nowadays, the use of semiochemicals, in particular the major component of the sex pheromone, (E,Z)-7.9-dodecadienil acetate, are part of mating disruption methods to control L. botrana. How insect pests can recognize these molecules, is being part of huge efforts to deorphanize their olfactory mechanism at molecular level. Thus, an interesting group of proteins has been identified in the antennae of insects, where odorant-binding proteins (OBPs) are known by transporting molecules to odorant receptors (ORs) and a co-receptor (ORCO) causing a behavioral change in the insect. Other proteins such as chemosensory proteins (CSPs), ionotropic receptors (IRs), odorant degrading enzymes (ODEs) and sensory neuron membrane proteins (SNMPs) seem to be involved, but few studies have been performed so far. The above has led to an increasing interest in insect communication at a molecular level, which has contributed to both a better understanding of the olfaction process and the design of new pest management strategies. To date, it has been reported that the ORs can detect one or a small group of odorants in a specific way. Therefore, the objective of this study is the identification of genes that encode these ORs using the antennal transcriptome of L. botrana. Total RNA was extracted for females and males of L. botrana, and the antennal transcriptome sequenced by Next Generation Sequencing service using an Illumina HiSeq2500 platform with 50 million reads per sample. Unigenes were assembled using Trinity v2.4.0 package and transcript abundance was obtained using edgeR. Genes were identified using BLASTN and BLASTX locally installed in a Unix system and based on our own Tortricidae database. Those Unigenes related to ORs were characterized using ORFfinder and protein Blastp server. Finally, a phylogenetic analysis was performed with the candidate amino acid sequences for LbotORs including amino acid sequences of other moths ORs, such as Bombyx mori, Cydia pomonella, among others. Our findings suggest 61 genes encoding ORs and one gene encoding an ORCO in both sexes, where the greatest difference was found in the OR6 because of the transcript abundance according to the value of FPKM in females and males was 1.48 versus 324.00. In addition, according to phylogenetic analysis OR6 is closely related to OR1 in Cydia pomonella and OR6, OR7 in Epiphyas postvittana, which have been described as pheromonal receptors (PRs). These results represent the first evidence of ORs present in the antennae of L. botrana and a suitable starting point for further functional studies with selected ORs, such as OR6, which is potentially related to pheromonal recognition.

Keywords: antennal transcriptome, lobesia botrana, odorant receptors (ORs), phylogenetic analysis

Procedia PDF Downloads 200

Authors: A. Hakem, Y. Bouafia

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Characterization of materials used for various mechanical components is of great importance in their design. Several studies were conducted by various authors in order to improve their physical and/or chemical properties in general and mechanical or metallurgical properties in particular. The foundry alloy AlSi7Zn3Cu2Mg is one of the main components constituting the various mechanisms for the implementation of applications and various industrial projects. Obtaining a reliable product is not an easy task; several results proposed by different authors show sometimes results that can contradictory. Due to their high mechanical characteristics, these alloys are widely used in engineering. Silicon improves casting properties and magnesium allows heat treatment. It is thus possible to obtain various degrees of hardening and therefore interesting compromise between tensile strength and yield strength, on one hand, and elongation, on the other hand. These mechanical characteristics can be further enhanced by a series of mechanical treatments or heat treatments. Their light weight coupled with high mechanical characteristics, aluminum alloys are very much used in cars and aircraft industry. The present study is focused on the influence of heat treatments which cause significant micro structural changes, usually hardening by variation of annealing temperatures by increments of 10°C and 20°C on the evolution of the main elastic characteristics, the resistance, the ductility and the structural characteristics of AlSi7Zn3Cu2Mg foundry alloy cast in sand by gravity. These elastic properties are determined in three directions for each specimen of dimensions 200x150x20 mm³ by the ultrasonic method based on acoustic or elastic waves. The hardness, the micro hardness and the structural characteristics are evaluated by a non-destructive method. The aim of this work is to study the hardening ability of AlSi7Zn3Cu2Mg alloy by considering ten states. To improve the mechanical properties obtained with the raw casting, one should use heat treatment for structural hardening; the addition of magnesium is necessary to increase the sensitivity to this specific heat treatment: Treatment followed by homogenization which generates a diffusion of atoms in a substitution solid solution inside a hardening furnace at 500°C during 8h, followed immediately by quenching in water at room temperature 20 to 25°C, then an ageing process for 17h at room temperature and at different annealing temperature (150, 160, 170, 180, 190, 240, 200, 220 and 240°C) for 20h in an annealing oven. The specimens were allowed to cool inside the oven.

Keywords: aluminum, foundry alloy, magnesium, mechanical characteristics, silicon

Procedia PDF Downloads 264

Authors: Esther Friedlander, Philip Friedlander

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The use of immunotherapy that inhibits programmed death-1 (PD-1) or its ligand PD-L1 confers survival benefits in patients with non-small cell lung cancer (NSCLC). However, approximately 45% of patients experience primary treatment resistance, necessitating the development of strategies to improve efficacy. While the renin-angiotensin system (RAS) has systemic hemodynamic effects, tissue-specific regulation exists along with modulation of immune activity in part through regulation of myeloid cell activity, leading to the hypothesis that RAS inhibition may improve anti-PD-1/L-1 efficacy. A retrospective analysis was conducted that included 173 advanced solid tumor cancer patients treated at Valley Hospital, a community Hospital in New Jersey, USA, who were treated with a PD-1/L-1 inhibitor in a defined time period showing a statistically significant relationship between RAS pathway inhibition (RASi through concomitant treatment with an ACE inhibitor or angiotensin receptor blocker) and positive efficacy to the immunotherapy that was independent of age, gender and cancer type. Subset analysis revealed strong numerical benefit for efficacy in both patients with squamous and nonsquamous NSCLC as determined by documented clinician assessment of efficacy and by duration of therapy. A PUBMED literature search was now conducted to identify studies assessing the effect of RAS pathway inhibition on anti-PD-1/L1 efficacy in advanced solid tumor patients and compare these findings to those seen in the Valley Hospital retrospective study with a focus on NSCLC specifically. A total of 11 articles were identified assessing the effects of RAS pathway inhibition on the efficacy of checkpoint inhibitor immunotherapy in advanced cancer patients. Of the 11 studies, 10 assessed the effect on survival of RASi in the context of treatment with anti-PD-1/PD-L1, while one assessed the effect on CTLA-4 inhibition. Eight of the studies included patients with NSCLC, while the remaining 2 were specific to genitourinary malignancies. Of the 8 studies, two were specific to NSCLC patients, with the remaining 6 studies including a range of cancer types, of which NSCLC was one. Of these 6 studies, only 2 reported specific survival data for the NSCLC subpopulation. Patient characteristics, multivariate analysis data and efficacy data seen in the 2 NSLCLC specific studies and in the 2 basket studies, which provided data on the NSCLC subpopulation, were compared to that seen in the Valley Hospital retrospective study supporting a broader effect of RASi on anti-PD-1/L1 efficacy in advanced NSLCLC with the majority of studies showing statistically significant benefit or strong statistical trends but with one study demonstrating worsened outcomes. This comparison of studies extends published findings to the community hospital setting and supports prospective assessment through randomized clinical trials of efficacy in NSCLC patients with pharmacodynamic components to determine the effect on immune cell activity in tumors and on the composition of the tumor microenvironment.

Keywords: immunotherapy, cancer, angiotensin, efficacy, PD-1, lung cancer, NSCLC

Procedia PDF Downloads 69

Authors: H. Bhuyan, S. Mändl, M. Favre, M. Cisternas, A. Henriquez, E. Wyndham, M. Walczak, D. Manova

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The 470 Li-24 Cr and 460Li-21 Cr are two alloys belonging to the next generation of super-ferritic nickel free stainless steel grades, containing titanium (Ti), niobium (Nb) and small percentage of carbon (C) and nitrogen (N). The addition of Ti and Nb improves in general the corrosion resistance while the low interstitial content of C and N assures finer precipitates and greater ductility compared to conventional ferritic grades. These grades are considered an economic alternative to AISI 316L and 304 due to comparable or superior corrosion. However, since 316L and 304 can be nitrided to improve the mechanical surface properties like hardness and wear; it is hypothesize that the tribological properties of these super-ferritic stainless steels grades can also be improved by plasma nitriding. Thus two sets of plasma immersion ion implantation experiments have been carried out, one with a high pressure capacitively coupled radio frequency plasma at PUC Chile and the other using a low pressure microwave plasma at IOM Leipzig, in order to explore further improvements in the mechanical properties of 470 Li-24 Cr and 460Li-21 Cr steel. Nitrided and unnitrided substrates have been subsequently investigated using different surface characterization techniques including secondary ion mass spectroscopy, scanning electron microscopy, energy dispersive x-ray analysis, Vickers hardness, wear resistance, as well as corrosion test. In most of the characterizations no major differences have been observed for nitrided 470 Li-24 Cr and 460Li-21 Cr. Due to the ion bombardment, an increase in the surface roughness is observed for higher treatment temperature, independent of the steel types. The formation of chromium nitride compound takes place only at a treatment temperature around 4000C-4500C, or above. However, corrosion properties deteriorate after treatment at higher temperatures. The physical characterization results show up to 25 at.% of nitrogen for a diffusion zone of 4-6 m, and a 4-5 times increase in hardness for different experimental conditions. The samples implanted with temperature higher than 400 °C presented a wear resistance around two orders of magnitude higher than the untreated substrates. The hardness is apparently affected by the different roughness of the samples and their different profile of nitrogen.

Keywords: ion implantation, plasma, RF and microwave plasma, stainless steel

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Authors: Satwik Majumder, Dongyun Jung, Jennifer Ronholm, Saji George

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Bovine mastitis is the most common infectious disease in dairy cattle, with major economic implications for the dairy industry worldwide. Continuous monitoring for the emergence of antimicrobial resistance (AMR) among bacterial isolates from dairy farms is vital not only for animal husbandry but also for public health. In this study, the prevalence of AMR in 113 Escherichia coli isolates from cases of bovine clinical mastitis in Canada was investigated. Kirby-Bauer disk diffusion test with 18 antibiotics and microdilution method with three heavy metals (copper, zinc, and silver) was performed to determine the antibiotic and heavy-metal susceptibility. Resistant strains were assessed for efflux and ß-lactamase activities besides assessing biofilm formation and hemolysis. Whole-genome sequences for each of the isolates were examined to detect the presence of genes corresponding to the observed AMR and virulence factors. Phenotypic analysis revealed that 32 isolates were resistant to one or more antibiotics, and 107 showed resistance against at least one heavy metal. Quinolones and silver were the most efficient against the tested isolates. Among the AMR isolates, AcrAB-TolC efflux activity and ß-lactamase enzyme activities were detected in 13 and 14 isolates, respectively. All isolates produced biofilm but with different capacities, and 33 isolates showed α-hemolysin activity. A positive correlation (Pearson r = +0.89) between efflux pump activity and quantity of biofilm was observed. Genes associated with aggregation, adhesion, cyclic di-GMP, quorum sensing were detected in the AMR isolates, corroborating phenotype observations. This investigation showed the prevalence of AMR in E. coli isolates from bovine clinical mastitis. The results also suggest the inadequacy of antimicrobials with a single mode of action to curtail AMR bacteria with multiple mechanisms of resistance and virulence factors. Therefore, it calls for combinatorial therapy for the effective management of AMR infections in dairy farms and combats its potential transmission to the food supply chain through milk and dairy products.

Keywords: antimicrobial resistance, E. coli, bovine mastitis, antibiotics, heavy-metals, efflux pump, ß-lactamase enzyme, biofilm, whole-genome sequencing

Procedia PDF Downloads 216

Authors: Pampita Chakraborty, Sukumar Mukherjee

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Diabetes Mellitus (DM) is commonly encountered metabolic disorder in clinical practice. An estimated 25 percent of DM patients develop foot problems. Foot ulceration and infection are one of the major causes of morbidity, hospitalization or even amputation. Objective: To isolate and identify bacterial pathogens in Diabetic Foot Ulcer (DFU) and to observe its antimicrobial sensitivity pattern. Methodology: A prospective study was conducted for a period of 9 months at the Department of Microbiology, GD Hospital & Diabetes Institute, Kolkata. 75 DFU patients were recruited in the study. Specimens for microbiological studies obtained from ulcer base were examined as gram stained smear and was cultured aerobically on Nutrient agar, Blood agar and MacConkey agar plates. Antimicrobial sensitivity test was performed by disc diffusion techniques according to CLSI guidelines. Result: In this study out of 75cases, 73% (55/75) were male and 27% (20/75) were females with mean (SD) age of 51.11(±10) years. Out of 75 pus cultures, 63(84%) showed growth of microorganism making total of 81 bacterial isolates with 71.42% of monomicrobial infection and 28.57% of polymicrobial infection. Out of 81 isolates 53(65.43%) were gram negative and 21(25.92%) were gram positive. E.coli was relatively common isolate 21(26%) followed by Staphylococcus aureus 15(18.5%), Klebsiella pneumonia 14(17.28%), Pseudomonas aeruginosa 12 (14.81%), Proteus spp. 3 (3.70%), and Enterococcus faecalis 6 (7.40%). 75% of Gram-negative microorganism were extended Beta-lactamase enzyme (ESBL) producer and around 20 % of Klebsiella and Proteus spp. were carbapenemase enzyme producer. Among Gram positive, around 50% of S.aureus was MRSA, sensitive only to Vancomycin, Teicoplanin & Linezolid. Conclusion: More prevalence of monomicrobial gram-negative bacteria than gram-positive bacteria in DFU was observed. This study emphasizes that Beta-Lactam group of antibiotics should not be the empirical treatment of choice for Gram-negative isolates; instead alternatives like Carbapenems, Amikacin could be a better option. On the other hand, Vancomycin and Linezolid are preferred for most of the infection with gram-positive aerobes. Continuous surveillance of resistant bacteria is required for empiric therapy.

Keywords: antibiotic resistant, antimicrobial susceptibility, diabetic foot ulcer, surveillance

Procedia PDF Downloads 369

Authors: Ade O. Oyewole, Sunday O. Okoh, Ruth O. Ishola, Adenike D. Odusote, Chima C. Igwe, Gloria N. Elemo, Anthony I. Okoh

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Azadirachta indica (Neem tree) also referred to as an all-purpose tree is used in a wide range of medical preparations in tropical and subtropical countries for prevention and management of various livestock, crops products and human diseases. In Nigeria however, the potentials of this plant have not been fully exploited thus it causes an environmental nuisance during the fruiting season. With a rise in the demand for herbal personal care products globally extracts from different parts of the neem plant were used as the bio-active ingredients in the formulation of personal care products. In this study, formulated neem soap, body cream, lotion, toothpaste and shampoo are analyzed to determine their antibacterial, antifungal, and toxicity properties. The efficacies of these products for management of infectious diseases, both oral and dermal, were also investigated in vitro. Oil from the neem seeds obtained using a mechanical press and acetone extracts of both the neem bark and leaves obtained by the maceration method were used in the formulation and production of the neem personal care products. The antimicrobial and toxicity properties of these products were investigated by agar diffusion, and haemolytic methods respectively. The five neem products (NPs) exhibited strong antibacterial activities against four multi–drug resistant pathogenic and three none pathogenic bacterial strains (Escherichia coli (180), Listeria ivanovii, Staphylococcus aureus, Enterobacter cloacae, Vibro spp., Streptococcus uberis, Mycobacterium smegmatis), except the neem lotion with insignificant activity against E. coli and S. aureus. The minimum inhibitory concentration (MIC) range was between 0.20-0.40 mg/ mL. The 5 NPs demonstrated moderate activity against three clinical dermatophytes isolates (Tinea corporis, Tinea capitis, and Tinea cruiz) as well as one fungal strain (Candida albican) with the MIC ranging between 0.30 - 0.50 mg/ mL and 0.550 mg/mL respectively. The soap and shampoo were the most active against test bacteria and fungi. The haemolytic analysis results on the 5 NPs indicated none toxicity at 0.50 mg/ mL in sheep red blood cells (SRBC).

Keywords: antimicrobial, Azadirachta indica, multi–drug resistant pathogenic bacteria, personal care products

Procedia PDF Downloads 270

Authors: Rammah Abdlbagi, Egmen Tazcan, Kiriti Tripathi, Vinayagam Sudhakar, Thomas Swallow, Aakash Pai

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Introduction and Objectives: MRI has an increasing role in the diagnosis and staging of prostate cancer. Multiparametric MRI includes multiple sequences, including T2 weighting, diffusion weighting, and dynamic contrast enhancement (DCE). Administration of DCE is expensive, time-consuming, and requires medical supervision due to the risk of anaphylaxis. Biparametric MRI (bpMRI), without DCE, overcomes many of these issues; however, there is conflicting data on its accuracy. Furthermore, data on the concordance between bpMRI lesion and pathology specimen, as well as the rates of cancer stage upgrading after surgery, is limited within the available literature. This study aims to examine the diagnostic test accuracy of bpMRI in the diagnosis of prostate cancer and radiological assessment of prostate cancer staging. Specifically, we aimed to evaluate the ability of bpMRI to accurately localise malignant lesions to better understand its accuracy and application in MRI-targeted biopsies. Materials and Methods: One hundred and forty patients who underwent bpMRI prior to radical prostatectomy (RP) were retrospectively reviewed from a single institution. Histological grade from the prostate biopsy was compared with surgical specimens from RP. Clinically significant prostate cancer (csPCa) was defined as Gleason grade group ≥2. bpMRI staging was compared with RP histology. Results: Overall sensitivity of bpMRI in diagnosing csPCa independent of location and staging was 98.87%. Of the 140 patients, 29 (20.71%) had their prostate biopsy histology upgraded at RP. 61 (43.57%) patients had csPca noted on RP specimens in areas that were not identified on the bpMRI. 55 (39.29%) had upstaging after RP from the original staging with bpMRI. Conclusions: Whilst the overall sensitivity of bpMRI in predicting any clinically significant cancer was good, there was notably poor concordance in the location of the tumour between bpMRI and eventual RP specimen. The results suggest that caution should be exercised when using bpMRI for targeted prostate biopsies and validates the continued role of systemic biopsies. Furthermore, a significant number of patients were upstaged at RP from their original staging with bpMRI. Based on these findings, bpMRI results should be interpreted with caution and can underestimate TNM stage, requiring careful consideration of treatment strategy.

Keywords: biparametric MRI, Ca prostate, staging, post prostatectomy histology

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Authors: Autumn Rooms Cypres, Barbara Driver

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The purpose of this study is to extend discussions about innovations and career politics. Research questions that grounded this effort were: How does an academic learn the unspoken rules of the academy? What happens politically to an academic’s career when their research speaks against the grain of society? Do professors perceive signals that it is time to move on to another institution or even to another career? Epistemology and Methods: This qualitative investigation was focused on examining perceptions of academics. Therefore an open-ended field study, based on Grounded Theory, was used. This naturalistic paradigm (Lincoln & Guba,1985) was selected because it tends to understand information in terms of whole, of patterns, and in relations to the context of the environment. The technique for gathering data was the process of semi-structured, in-depth interviewing. Twenty five academics across the United States were interviewed relative to their career trajectories and the politics and opportunities they have encountered in relation to their research efforts. Findings: The analysis of interviews revealed four themes: Academics are beholden to 2 specific networks of power that influence their sense of job security; the local network based on their employing university and the national network of scholars who share the same field of research. The fights over what counts as research can and does drift from the intellectual to the political, and personal. Academic were able to identify specific instances of shunning and or punishment from their colleagues related directly to the dissemination of research that spoke against the grain of the local or national networks. Academics identified specific signals from both of these networks indicating that their career was flourishing or withering. Implications: This research examined insights from those who persevered when the fights over what and who counts drifted from the intellectual to the political, and the personal. Considerations of why such drifts happen were offered in the form of a socio-political construct called Fit, which included thoughts on hegemony, discourse, and identity. This effort reveals the importance of understanding what professional capital is relative to job security. It also reveals that fear is an enmeshed and often unspoken part of the culture of Academia. Further research to triangulate these findings would be helpful within international contexts.

Keywords: politics, academia, job security, context

Procedia PDF Downloads 321

Authors: Niklas Ravn-Boess, Nainita Bhowmick, Takamitsu Hattori, Shohei Koide, Christopher Park, Dimitris Placantonakis

Abstract:

Background: Glioblastoma (GBM) is the most common and deadly primary brain malignancy in adults. Tumor propagation, brain invasion, and resistance to therapy critically depend on GBM stem-like cells (GSCs); however, the mechanisms that regulate GSC self-renewal are incompletely understood. Given the aggressiveness and poor prognosis of GBM, it is imperative to find biomarkers that could also translate into novel drug targets. Along these lines, we have identified a cell surface antigen, CD97 (ADGRE5), an adhesion G protein-coupled receptor (GPCR), that is expressed on GBM cells but is absent from non-neoplastic brain tissue. CD97 has been shown to promote invasiveness, angiogenesis, and migration in several human cancers, but its frequency of expression and functional role in regulating GBM growth and survival, and its potential as a therapeutic target has not been investigated. Design: We assessed CD97 mRNA and protein expression in patient derived GBM samples and cell lines using publicly available RNA-sequencing datasets and flow cytometry, respectively. To assess CD97 function, we generated shRNA lentiviral constructs that target a sequence in the CD97 extracellular domain (ECD). A scrambled shRNA (scr) with no predicted targets in the genome was used as a control. We evaluated CD97 shRNA lentivirally transduced GBM cells for Ki67, Annexin V, and DAPI. We also tested CD97 KD cells for their ability to self-renew using clonogenic tumorsphere formation assays. Further, we utilized synthetic Abs (sAbs) generated against the ECD of CD97 to test for potential antitumor effects using patient-derived GBM cell lines. Results: CD97 mRNA expression was expressed at high levels in all GBM samples available in the TCGA cohort. We found high levels of surface CD97 protein expression in 6/6 patient-derived GBM cell cultures, but not human neural stem cells. Flow cytometry confirmed downregulation of CD97 in CD97 shRNA lentivirally transduced cells. CD97 KD induced a significant reduction in cell growth in 3 independent GBM cell lines representing mesenchymal and proneural subtypes, which was accompanied by reduced (~20%) Ki67 staining and increased (~30%) apoptosis. Incubation of GBM cells with sAbs (20 ug/ ml) against the ECD of CD97 for 3 days induced GSC differentiation, as determined by the expression of GFAP and Tubulin. Using three unique GBM patient derived cultures, we found that CD97 KD attenuated the ability of GBM cells to initiate sphere formation by over 300 fold, consistent with an impairment in GSC self-renewal. Conclusion: Loss of CD97 expression in patient-derived GBM cells markedly decreases proliferation, induces cell death, and reduces tumorsphere formation. sAbs against the ECD of CD97 reduce tumorsphere formation, recapitulating the phenotype of CD97 KD, suggesting that sAbs that inhibit CD97 function exhibit anti-tumor activity. Collectively, these findings indicate that CD97 is necessary for the proliferation and survival of human GBM cells and identify CD97 as a promising therapeutically targetable vulnerability in GBM.

Keywords: adhesion GPCR, CD97, GBM stem cell, glioblastoma

Procedia PDF Downloads 137

Authors: Kubilay Kurtulus Bastas

Abstract:

Bacterial diseases are very destructive and cause economic losses on pears. Promising plant extracts for the management of plant diseases are environmentally safe, long-lasting and extracts of certain plants contain alkaloids, tannins, quinones, coumarins, phenolic compounds, and phytoalexins. In this study, bacteria were isolated from different parts of pear exhibiting characteristic symptoms of bacterial diseases from the Central Anatolia, Turkey. Pathogenic bacteria were identified by morphological, physiological, biochemical and molecular methods as fire blight (Erwinia amylovora (39%)), bacterial blossom blast and blister bark (Pseudomonas syringae pv. syringae (22%)), crown gall (Rhizobium radiobacter (1%)) from different pear cultivars, and determined virulence levels of the pathogens with pathogenicity tests. The air-dried 25 plant material was ground into fine powder and extraction was performed at room temperature by maceration with 80% (v/v) methanol/distilled water. The minimum inhibitory concentration (MIC) values were determined by using modified disc diffusion method at five different concentrations and streptomycin sulphate was used as control chemical. Bacterial suspensions were prepared as 108 CFU ml⁻¹ densities and 100 µl bacterial suspensions were spread to TSA medium. Antimicrobial activity was evaluated by measuring the inhibition zones in reference to the test organisms. Among the tested plants, Origanum vulgare, Hedera helix, Satureja hortensis, Rhus coriaria, Eucalyptus globulus, Rosmarinus officinalis, Ocimum basilicum, Salvia officinalis, Cuminum cyminum and Thymus vulgaris showed a good antibacterial activity and they inhibited the growth of the pathogens with inhibition zone diameter ranging from 7 to 27 mm at 20% (w/v) in absolute methanol in vitro conditions. In vivo, the highest efficacy was determined as 27% on reducing tumor formation of R. radiobacter, and 48% and 41% on reducing shoot blight of E. amylovora and P. s. pv. syringae on pear seedlings, respectively. Obtaining data indicated that some plant extracts may be used against the bacterial diseases on pome fruits within sustainable and organic management programs.

Keywords: bacteria, eco-friendly management, organic, pear, plant extract

Procedia PDF Downloads 335

Authors: Habtamu Garoma Debela, Gemechis File Duressa

Abstract:

In this work, our primary interest is to provide ε-uniformly convergent numerical techniques for solving singularly perturbed semilinear boundary value problems with non-local boundary condition. These singular perturbation problems are described by differential equations in which the highest-order derivative is multiplied by an arbitrarily small parameter ε (say) known as singular perturbation parameter. This leads to the existence of boundary layers, which are basically narrow regions in the neighborhood of the boundary of the domain, where the gradient of the solution becomes steep as the perturbation parameter tends to zero. Due to the appearance of the layer phenomena, it is a challenging task to provide ε-uniform numerical methods. The term 'ε-uniform' refers to identify those numerical methods in which the approximate solution converges to the corresponding exact solution (measured to the supremum norm) independently with respect to the perturbation parameter ε. Thus, the purpose of this work is to develop, analyze, and improve the ε-uniform numerical methods for solving singularly perturbed problems. These methods are based on nonstandard fitted finite difference method. The basic idea behind the fitted operator, finite difference method, is to replace the denominator functions of the classical derivatives with positive functions derived in such a way that they capture some notable properties of the governing differential equation. A uniformly convergent numerical method is constructed via nonstandard fitted operator numerical method and numerical integration methods to solve the problem. The non-local boundary condition is treated using numerical integration techniques. Additionally, Richardson extrapolation technique, which improves the first-order accuracy of the standard scheme to second-order convergence, is applied for singularly perturbed convection-diffusion problems using the proposed numerical method. Maximum absolute errors and rates of convergence for different values of perturbation parameter and mesh sizes are tabulated for the numerical example considered. The method is shown to be ε-uniformly convergent. Finally, extensive numerical experiments are conducted which support all of our theoretical findings. A concise conclusion is provided at the end of this work.

Keywords: nonlocal boundary condition, nonstandard fitted operator, semilinear problem, singular perturbation, uniformly convergent

Procedia PDF Downloads 143