Search results for: selective serotonin reuptake inhibitors (SSRIs)

Authors: Cristina Diaz, Lucia Perez, Simone Visigalli, Giuseppe Di Florio, Gonzalo Fuentes, Roberto Canziani, Paolo Gronchi

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During the last 50 years, the selection of materials is one of the main decisions in machine design for different industrial applications. It is due to numerous physical, chemical, mechanical and technological factors to consider in it. Corrosion effects are related with all of these factors and impact in the life cycle, machine incidences and the costs for the life of the machine. Corrosion affects the deterioration or destruction of metals due to the reaction with the environment, generally wet. In food industry, dewatering industry, concrete industry, paper industry, etc. corrosion is an unsolved problem and it might introduce some alterations of some characteristics in the final product. Nowadays, depending on the selected metal, its surface and its environment of work, corrosion prevention might be a change of metal, use a coating, cathodic protection, use of corrosion inhibitors, etc. In the vast majority of the situations, use of a corrosion resistant material or in its defect, a corrosion protection coating is the solution. Stainless steels are widely used in machine design, because of their strength, easily cleaned capacity, corrosion resistance and appearance. Typical used are AISI 304 and AISI 316. However, their benefits don’t fit every application, and some coatings are required against corrosion such as some paintings, galvanizing, chrome plating, SiO₂, TiO₂ or ZrO₂ coatings, etc. In this work, some coatings based in a bilayer made of Titanium-Tantalum, Titanium-Niobium, Titanium-Hafnium or Titanium-Zirconium, have been developed used magnetron sputtering configuration by PVD (Physical Vapor Deposition) technology, for trying to reduce corrosion effects on AISI 304, AISI 316 and comparing it with Titanium alloy substrates. Ti alloy display exceptional corrosion resistance to chlorides, sour and oxidising acidic media and seawater. In this study, Ti alloy (99%) has been included for comparison with coated AISI 304 and AISI 316 stainless steel. Corrosion tests were conducted by a Gamry Instrument under ASTM G5-94 standard, using different electrolytes such as tomato salsa, wine, olive oil, wet compost, a mix of sand and concrete with water and NaCl for testing corrosion in different industrial environments. In general, in all tested environments, the results showed an improvement of corrosion resistance of all coated AISI 304 and AISI 316 stainless steel substrates when they were compared to uncoated stainless steel substrates. After that, comparing these results with corrosion studies on uncoated Ti alloy substrate, it was observed that in some cases, coated stainless steel substrates, reached similar current density that uncoated Ti alloy. Moreover, Titanium-Zirconium and Titanium-Tantalum coatings showed for all substrates in study including coated Ti alloy substrates, a reduction in current density more than two order in magnitude. As conclusion, Ti-Ta, Ti-Zr, Ti-Nb and Ti-Hf coatings have been developed for improving corrosion resistance of AISI 304 and AISI 316 materials. After corrosion tests in several industry environments, substrates have shown improvements on corrosion resistance. Similar processes have been carried out in Ti alloy (99%) substrates. Coated AISI 304 and AISI 316 stainless steel, might reach similar corrosion protection on the surface than uncoated Ti alloy (99%). Moreover, coated Ti Alloy (99%) might increase its corrosion resistance using these coatings.

Keywords: coatings, corrosion, PVD, stainless steel

Procedia PDF Downloads 129

Authors: Tomasz Łęga, Marta Sosnowska, Mirosława Panasiuk, Lilit Hovhannisyan, Beata Gromadzka, Marcin Olszewski, Sabina Zoledowska, Dawid Nidzworski

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Toxic heavy metal ion contamination of industrial wastewater has recently become a significant environmental concern in many regions of the world. Although the majority of heavy metals are naturally occurring elements found on the earth's surface, anthropogenic activities such as mining and smelting, industrial production, and agricultural use of metals and metal-containing compounds are responsible for the majority of environmental contamination and human exposure. The permissible limits (ppm) for heavy metals in food, water and soil are frequently exceeded and considered hazardous to humans, other organisms, and the environment as a whole. Human exposure to highly nickel-polluted environments causes a variety of pathologic effects. In 2008, nickel received the shameful name of “Allergen of the Year” (GILLETTE 2008). According to the dermatologist, the frequency of nickel allergy is still growing, and it can’t be explained only by fashionable piercing and nickel devices used in medicine (like coronary stents and endoprostheses). Effective remediation methods for removing heavy metal ions from soil and water are becoming increasingly important. Among others, methods such as chemical precipitation, micro- and nanofiltration, membrane separation, conventional coagulation, electrodialysis, ion exchange, reverse and forward osmosis, photocatalysis and polymer or carbon nanocomposite absorbents have all been investigated so far. The importance of environmentally sustainable industrial production processes and the conservation of dwindling natural resources has highlighted the need for affordable, innovative biosorptive materials capable of recovering specific chemical elements from dilute aqueous solutions. The use of combinatorial phage display techniques for selecting and recognizing material-binding peptides with a selective affinity for any target, particularly inorganic materials, has gained considerable interest in the development of advanced bio- or nano-materials. However, due to the limitations of phage display libraries and the biopanning process, the accuracy of molecular recognition for inorganic materials remains a challenge. This study presents the isolation, identification and characterisation of metal binding phage clones that preferentially recover nickel.

Keywords: Heavy metal recovery, cleaning water, phage display, nickel

Procedia PDF Downloads 73

Authors: Murad A. Channa, Mehdi Khiadani. Yasir Al-Abdeli

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Considering the severity of water scarcity around the world and its widening at an alarming rate, practical improvements in desalination techniques need to be engineered at the earliest. Atomization is the major aspect of flashing phenomena, yet it has been paid less attention to until now. There is a need to test efficient ways of atomization for the flashing process. Flash evaporation together with reverse osmosis is also a commercially matured desalination technique commonly famous as Multi-stage Flash (MSF). Even though reverse osmosis is massively practical, it is not economical or sustainable compared to flash evaporation. However, flashing evaporation has its drawbacks as well such as lower efficiency of water production per higher consumption of power and time. Flash evaporation is simply the instant boiling of a subcooled liquid which is introduced as droplets in a well-maintained negative environment. This negative pressure inside the vacuum increases the temperature of the liquid droplets far above their boiling point, which results in the release of latent heat, and the liquid droplets turn into vapor which is collected to be condensed back into an impurity-free liquid in a condenser. Atomization is the main difference between pool and spray flash evaporation. Atomization is the heart of the flash evaporation process as it increases the evaporating surface area per drop atomized. Atomization can be categorized into many levels depending on its drop size, which again becomes crucial for increasing the droplet density (drop count) per given flow rate. This review comprehensively summarizes the selective results relating to the methods of atomization and their effectiveness on the evaporation rate from earlier works to date. In addition, the reviewers propose using centrifugal atomization for the flashing application, which brings several advantages viz ultra-fine droplets, uniform droplet density, and the swirling geometry of the spray with kinetically more energetic sprays during their flight. Finally, several challenges of using rotary bell atomizer (RBA) and RBA Sprays inside the chamber have been identified which will be explored in detail. A schematic of rotary bell atomizer (RBA) integration with the chamber has been designed. This powerful centrifugal atomization has the potential to increase potable water production in commercial multi-stage flash evaporators, where it would be preferably advantageous.

Keywords: atomization, desalination, flash evaporation, rotary bell atomizer

Procedia PDF Downloads 51

Authors: Damtew Samson Zerihun

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This paper primarily describes the concept of a hierarchical safety control (HSC) in discrete manufacturing to up-hold productivity with human intervention and machine failures using a systematic approach, through increasing the system availability and using additional knowledge on machines so as to improve the human machine collaboration (HMC). It also highlights the implemented PLC safety algorithm, in applying this generic concept to a concrete pro-duction line using a lab demonstrator called FATIE (Factory Automation Test and Integration Environment). Furthermore, the paper describes a model and provide a systematic representation of human-machine collabora-tion in discrete manufacturing and to this end, the Hierarchical Safety Control concept is proposed. This offers a ge-neric description of human-machine collaboration based on Finite State Machines (FSM) that can be applied to vari-ous discrete manufacturing lines instead of using ad-hoc solutions for each line. With its reusability, flexibility, and extendibility, the Hierarchical Safety Control scheme allows upholding productivity while maintaining safety with reduced engineering effort compared to existing solutions. The approach to the solution begins with a successful partitioning of different zones around the Integrated Manufacturing System (IMS), which are defined by operator tasks and the risk assessment, used to describe the location of the human operator and thus to identify the related po-tential hazards and trigger the corresponding safety functions to mitigate it. This includes selective reduced speed zones and stop zones, and in addition with the hierarchical safety control scheme and advanced safety functions such as safe standstill and safe reduced speed are used to achieve the main goals in improving the safe Human Ma-chine Collaboration and increasing the productivity. In a sample scenarios, It is shown that an increase of productivity in the order of 2.5% is already possible with a hi-erarchical safety control, which consequently under a given assumptions, a total sum of 213 € could be saved for each intervention, compared to a protective stop reaction. Thereby the loss is reduced by 22.8%, if occasional haz-ard can be refined in a hierarchical way. Furthermore, production downtime due to temporary unavailability of safety devices can be avoided with safety failover that can save millions per year. Moreover, the paper highlights the proof of the development, implementation and application of the concept on the lab demonstrator (FATIE), where it is realized on the new safety PLCs, Drive Units, HMI as well as Safety devices in addition to the main components of the IMS.

Keywords: discrete automation, hierarchical safety controller, human machine collaboration, programmable logical controller

Procedia PDF Downloads 350

Authors: Ana Carolina Kogawa, Selma Gutierrez Antonio, Hérida Regina Nunes Salgado

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Rifaximin is an oral antimicrobial, gut - selective and not systemic with adverse effects compared to placebo. It is used for the treatment of hepatic encephalopathy, travelers diarrhea, irritable bowel syndrome, Clostridium difficile, ulcerative colitis and acute diarrhea. The crystalline form present in the rifaximin with minimal systemic absorption is α, being the amorphous form significantly different. Regulators are increasingly attention to polymorphisms. Polymorphs can change the form by altering the drug characteristics compromising the effectiveness and safety of the finished product. International Conference on Harmonization issued the ICH Guidance Q6A, which aim to improve the control of polymorphism in new and existing pharmaceuticals. The objective of this study was to obtain polymorphic forms of rifaximin employing recrystallization processes and characterize them by thermal analysis (thermogravimetry - TG and differential scanning calorimetry - DSC), X-ray diffraction, scanning electron microscopy and solubility test. Six polymorphic forms of rifaximin, designated I to VI were obtained by the crystallization process by evaporation of the solvent. The profiles of the TG curves obtained from polymorphic forms of rifaximin are similar to rifaximin and each other, however, the DTG are different, indicating different thermal behaviors. Melting temperature values of all the polymorphic forms were greater to that shown by the rifaximin, indicating the higher thermal stability of the obtained forms. The comparison of the diffractograms of the polymorphic forms of rifaximin with rifaximin α, β and γ constant in patent indicate that forms III, V and VI are formed by mixing polymorph β and α and form III is formed by polymorph β. The polymorphic form I is formed by polymorph β, but with a significant amount of amorphous material. Already, the polymorphic form II consists of polymorph γ, amorphous. In scanning electron microscope is possible to observe the heterogeneity of morphological characteristics of crystals of polymorphic forms among themselves and with rifaximin. The solubility of forms I and II was greater than the solubility of rifaximin, already, forms III, IV and V presented lower solubility than of rifaximin. Similarly, the bioavailability of the amorphous form of rifaximin is considered significantly higher than the form α, the polymorphic forms obtained in this work can not guarantee the excellent tolerability of the reference medicine. Therefore, studies like these are extremely important and they point to the need for greater requirements by the regulatory agencies competent about polymorphs analysis of the raw materials used in the manufacture of medicines marketed globally. These analyzes are not required in the majority of official compendia. Partnerships between industries, research centers and universities would be a viable way to consolidate researches in this area and contribute to improving the quality of solid drugs.

Keywords: electronic microscopy, polymorphism, rifaximin, solubility, X-ray diffraction

Procedia PDF Downloads 632

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

Procedia PDF Downloads 356

Authors: Lisa Shambare, Jean Mulopo, Sehliselo Ndlovu

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One of the major challenges of sustainable development is promoting an industry which is both ecologically durable and economically viable. This requires processes that are material and energy efficient whilst also being able to limit the production of waste and toxic effluents through effective methods of process synthesis and intensification. In South Africa and globally, both miniaturisation and technological advances have substantially increased the amount of electronic wastes (e-waste) generated annually. Vast amounts of e-waste are being generated yearly with only a minute quantity being recycled officially. The passion for electronic devices cannot ignore the scarcity and cost of mining the noble metal resources which contribute significantly to the efficiency of most electronic devices. It has hence become imperative especially in an African context that sustainable strategies which are environmentally friendly be developed for recycling of the noble metals from e-waste. This paper investigates the recovery of gold, silver and palladium from electronic wastes, which consists of a vast array of metals, using ionic liquids which have the potential of reducing the gaseous and aqueous emissions associated with existing hydrometallurgical and pyrometallurgical technologies while also maintaining the economy of the overall recycling scheme through solvent recovery. The ionic liquids 1-butyl-3-methyl imidazolium hydrogen sulphate (BmimHSO4) which behaves like a protic acid and was used in the present research for the selective leaching of gold and silver from e-waste. Different concentrations of the aqueous ionic liquid were used in the experiments ranging from 10% to 50%. Thiourea was used as the complexing agent in the investigation with Fe3+ as the oxidant. The pH of the reaction was maintained in the range of 0.8 to 1.5. The preliminary investigations conducted were successful in the leaching of silver and palladium at room temperature with optimum results being at 48hrs. The leaching results could not be explained because of the leaching of palladium with the absence of gold. Hence a conclusion could not be drawn and there was the need for further experiments to be run. The leaching of palladium was carried out with hydrogen peroxide as oxidant and 1-butyl-3-methyl imidazolium chloride (BmimCl) as the solvent. The experiments at carried out at a temperature of 60 degrees celsius and a very low pH. The chloride ion was used to complex with palladium metal. From the preliminary results, it could be concluded that pretreatment of the treatment e-waste was necessary to improve the efficiency of the metal recovery process. A conclusion could not be drawn for the leaching experiments.

Keywords: BmimCl, BmimHSO4, gold, palladium, silver

Procedia PDF Downloads 261

Authors: Fernandez liporace, Mercedes Uriel Fabiana

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Academic achievement in high school and college students is currently a matter of concern. National and international assessments show high schoolers as low achievers, and local statistics indicate alarming dropout percentages in this educational level. Even so, 80% of those students intend attending higher education. On the other hand, applications to Public National Universities are free and non-selective by examination procedures. Though initial registrations are massive (307.894 students), only 50% of freshmen pass their first year classes, and 23% achieves a degree. Low performances use to be a common problem. Hence, freshmen adaptation, their adjustment, dropout and low academic achievement arise as topics of agenda. Besides, the hinge between high school and college must be examined in depth, in order to get an integrated and successful path from one educational stratum to the other. Psychology aims at developing two main research lines to analyse the situation. One regarding psychometric scales, designing and/or adapting tests, examining their technical properties and their theoretical validity (e.g., academic motivation, learning strategies, learning styles, coping, perceived social support, parenting styles and parental consistency, paradoxical personality as correlated to creative skills, psychopathological symptomatology). The second research line emphasizes relationships within the variables measured by the former scales, facing the formulation and testing of predictive models of academic achievement, establishing differences by sex, age, educational level (high school vs college), and career. Pursuing these goals, several studies were carried out in recent years, reporting findings and producing assessment technology useful to detect students academically at risk as well as good achievers. Multiple samples were analysed totalizing more than 3500 participants (2500 from college and 1000 from high school), including descriptive, correlational, group differences and explicative designs. A brief on the most relevant results is presented. Providing information to design specific interventions according to every learner’s features and his/her educational environment comes up as a mid-term accomplishment. Furthermore, that information might be helpful to adapt curricula by career, as well as for implementing special didactic strategies differentiated by sex and personal characteristics.

Keywords: academic achievement, higher education, high school, psychological assessment

Procedia PDF Downloads 346

Authors: Maria Sciammarella, Uttam M. Shrestha, Youngho Seo, Grant T. Gullberg, Elias H. Botvinick

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Background: Myocardial perfusion imaging (MPI) is typically performed with static imaging protocols and visually assessed for perfusion defects based on the relative intensity distribution. Dynamic cardiac SPECT, on the other hand, is a new imaging technique that is based on time varying information of radiotracer distribution, which permits quantification of myocardial blood flow (MBF). In this abstract, we report a progress and current status of dynamic cardiac SPECT using conventional gamma camera (Infinia Hawkeye 4, GE Healthcare) for estimation of myocardial blood flow and coronary flow reserve. Methods: A group of patients who had high risk of coronary artery disease was enrolled to evaluate our methodology. A low-dose/high-dose rest/pharmacologic-induced-stress protocol was implemented. A standard rest and a standard stress radionuclide dose of ⁹⁹ᵐTc-tetrofosmin (140 keV) was administered. The dynamic SPECT data for each patient were reconstructed using the standard 4-dimensional maximum likelihood expectation maximization (ML-EM) algorithm. Acquired data were used to estimate the myocardial blood flow (MBF). The correspondence between flow values in the main coronary vasculature with myocardial segments defined by the standardized myocardial segmentation and nomenclature were derived. The coronary flow reserve, CFR, was defined as the ratio of stress to rest MBF values. CFR values estimated with SPECT were also validated with dynamic PET. Results: The range of territorial MBF in LAD, RCA, and LCX was 0.44 ml/min/g to 3.81 ml/min/g. The MBF between estimated with PET and SPECT in the group of independent cohort of 7 patients showed statistically significant correlation, r = 0.71 (p < 0.001). But the corresponding CFR correlation was moderate r = 0.39 yet statistically significant (p = 0.037). The mean stress MBF value was significantly lower for angiographically abnormal than that for the normal (Normal Mean MBF = 2.49 ± 0.61, Abnormal Mean MBF = 1.43 ± 0. 0.62, P < .001). Conclusions: The visually assessed image findings in clinical SPECT are subjective, and may not reflect direct physiologic measures of coronary lesion. The MBF and CFR measured with dynamic SPECT are fully objective and available only with the data generated from the dynamic SPECT method. A quantitative approach such as measuring CFR using dynamic SPECT imaging is a better mode of diagnosing CAD than visual assessment of stress and rest images from static SPECT images Coronary Flow Reserve.

Keywords: dynamic SPECT, clinical SPECT/CT, selective coronary angiograph, ⁹⁹ᵐTc-Tetrofosmin

Procedia PDF Downloads 134

Authors: D. Malouch, M. Berchel, C. Dreanno, S. Stachowski-Haberkorn, P-A. Jaffres

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Biofouling is a complex natural phenomenon that involves biological, physical and chemical properties related to the environment, the submerged surface and the living organisms involved. Bio-colonization of artificial structures can cause various economic and environmental impacts. The increase in costs associated with the over-consumption of fuel from biocolonized vessels has been widely studied. Measurement drifts from submerged sensors, as well as obstructions in heat exchangers, and deterioration of offshore structures are major difficulties that industries are dealing with. Therefore, surfaces that inhibit biocolonization are required in different areas (water treatment, marine paints, etc.) and many efforts have been devoted to produce efficient and eco-compatible antifouling agents. The different steps of surface fouling are widely described in literature. Studying the biofilm and its stages provides a better understanding of how to elaborate more efficient antifouling strategies. Several approaches are currently applied, such as the use of biocide anti-fouling paint (mainly with copper derivatives) and super-hydrophobic coatings. While these two processes are proving to be the most effective, they are not entirely satisfactory, especially in a context of a changing legislation. Nowadays, the challenge is to prevent biofouling with non-biocide compounds, offering a cost effective solution, but with no toxic effects on marine organisms. Since the micro-fouling phase plays an important role in the regulation of the following steps of biofilm formation, it is desired to reduce or delate biofouling of a given surface by inhibiting the micro-fouling at its early stages. In our recent works, we reported that some amphiphilic compounds exhibited bacteriostatic or bactericidal properties at a concentration that did not affect mammalian eukaryotic cells. These remarkable properties invited us to assess this type of bio-inspired phospholipids to prevent the colonization of surfaces by marine bacteria. Of note, other studies reported that amphiphilic compounds interacted with bacteria leading to a reduction of their development. An amphiphilic compound is a molecule consisting of a hydrophobic domain and a polar head (ionic or non-ionic). These compounds appear to have interesting antifouling properties: some ionic compounds have shown antimicrobial activity, and zwitterions can reduce nonspecific adsorption of proteins. Herein, we investigate the potential of amphiphilic compounds as inhibitors of bacterial growth and marine biofilm formation. The aim of this study is to compare the efficacy of four synthetic phospholipids that features a cationic charge or a zwitterionic polar-head group to prevent microfouling with marine bacteria. Toxicity of these compounds was also studied in order to identify the most promising compounds that inhibit biofilm development and show low cytotoxicity on two links representative of coastal marine food webs: phytoplankton and oyster larvae.

Keywords: amphiphilic phospholipids, biofilm, marine fouling, non-toxique assays

Procedia PDF Downloads 113

Authors: Homeira Asadi Kavan, Seyed Nasrollah Sajjadi, Mehrzade Hamidi, Hossein Rajabi, Mahdi Bigdely

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Positioning strategies of a sports brand can create a unique impression in the minds of the fans, sponsors, and other stakeholders. In order to influence potential customer's perception in an effective and positive way, a brands positioning strategy must be unique, credible, and relevant. Many sports clubs in Iran have been struggling to implement and achieve brand positioning accomplishments, due to different reasons such as lack of experience, scarcity of experts in the sports branding, and lack of related researches in this field. This study will provide a comprehensive theoretical framework and action plan for sport managers and marketers to design and implement effective brand positioning and to enable them to be distinguishable from competing brands and sports clubs. The study instrument is interviews with sports marketing and brand experts who have been working in this industry for a minimum of 20 years. Qualitative data analysis was performed using Atlast.ti text mining software version 7 and Open, axial and selective coding were employed to uncover and systematically analyze important and complex phenomena and elements. The findings show 199 effective elements in positioning strategies in Iran Professional Soccer League. These elements are categorized into 23 concepts and sub-categories as follows: Structural prerequisites, Strategic management prerequisites, Commercial prerequisites, Major external prerequisites, Brand personality, Club symbols, Emotional aspects, Event aspects, Fans’ strategies, Marketing information strategies, Marketing management strategies, Empowerment strategies, Executive management strategies, League context, Fans’ background, Market context, Club’s organizational context, Support context, Major contexts, Political-Legal elements, Economic factors, Social factors, and Technological factors. Eventually, the study model was developed by 6 main dimensions of Causal prerequisites, Axial Phenomenon (brand position), Strategies, Context Factors, Interfering Factors, and Consequences. Based on the findings, practical recommendations and strategies are suggested that can help club managers and marketers in developing and improving their respective sport clubs, brand positioning, and activities.

Keywords: brand positioning, soccer club, sport marketing, Iran professional soccer league, brand strategy

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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 43

Authors: Icaro V. Soares, Guilherme L. F. Brandao, Ursula D. C. Resende, Glaucio L. Siqueira

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Electrical energy can be wirelessly transmitted through resonant coupled coils that operate in the near-field region. Once in this region, the field has evanescent character, the efficiency of Resonant Wireless Power Transfer (RWPT) systems decreases proportionally with the inverse cube of distance between the transmitter and receiver coils. The commercially available RWPT systems are restricted to short and mid-range applications in which the distance between coils is lesser or equal to the coil size. An alternative to overcome this limitation is applying metamaterial structures to enhance the coupling between coils, thus reducing the field decay along the distance between them. Metamaterials can be conceived as composite materials with periodic or non-periodic structure whose unconventional electromagnetic behaviour is due to its unit cell disposition and chemical composition. This new kind of material has been used in frequency selective surfaces, invisibility cloaks, leaky-wave antennas, among other applications. However, for RWPT it is mainly applied as superlenses which are lenses that can overcome the optical limitation and are made of left-handed media, that is, a medium with negative magnetic permeability and electric permittivity. As RWPT systems usually operate at wavelengths of hundreds of meters, the metamaterial unit cell size is much smaller than the wavelength. In this case, electric and magnetic field are decoupled, therefore the double negative condition for superlenses are not required and the negative magnetic permeability is enough to produce an artificial magnetic medium. In this work, the influence of the magnetic permeability of a metamaterial slab inserted between two loosely coupled coils is studied in order to find the condition that leads to the maximum transmission efficiency. The metamaterial used is formed by a subwavelength unit cell that consist of a capacitor-loaded split ring with an inner spiral that is designed and optimized using the software Computer Simulation Technology. The unit cell permeability is experimentally characterized by the ratio of the transmission parameters between coils measured with and without the presence of the metamaterial slab. Early measurements results show that the transmission coefficient at the resonant frequency after the inclusion of the metamaterial is about three times higher than with just the two coils, which confirms the enhancement that this structure brings to RWPT systems.

Keywords: electromagnetic lens, loosely coupled coils, magnetic permeability, metamaterials, resonant wireless power transfer, subwavelength unit cells

Procedia PDF Downloads 125

Authors: Manohar Salla, Mark S. Butler, Ruby Pelingon, Geraldine Kaeslin, Daniel E. Croker, Janet C. Reid, Jong Min Baek, Paul V. Bernhardt, Elizabeth M. J. Gillam, Matthew A. Cooper, Avril A. B. Robertson

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MCC950 is a potent and selective inhibitor of the NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome that shows early promise for treatment of inflammatory diseases. The identification of major metabolites of lead molecule is an important step during drug development process. It provides an information about the metabolically labile sites in the molecule and thereby helping medicinal chemists to design metabolically stable molecules. To identify major metabolites of MCC950, the compound was incubated with human liver microsomes and subsequent analysis by (+)- and (−)-QTOF-ESI-MS/MS revealed a major metabolite formed due to hydroxylation on 1,2,3,5,6,7-hexahydro-s-indacene moiety of MCC950. This major metabolite can lose two water molecules and three possible regioisomers were synthesized. Co-elution of major metabolite with each of the synthesized compounds using HPLC-ESI-SRM-MS/MS revealed the structure of the metabolite (±) N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. Subsequent synthesis of individual enantiomers and coelution in HPLC-ESI-SRM-MS/MS using a chiral column revealed the metabolite was R-(+)- N-((1-hydroxy-1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-4-(2-hydroxypropan-2-yl)furan-2-sulfonamide. To study the possible cytochrome P450 enzyme(s) responsible for the formation of major metabolite, MCC950 was incubated with a panel of cytochrome P450 enzymes. The result indicated that CYP1A2, CYP2A6, CYP2B6, CYP2C9, CYP2C18, CYP2C19, CYP2J2 and CYP3A4 are most likely responsible for the formation of the major metabolite. The biological activity of the major metabolite and the other synthesized regioisomers was also investigated by screening for for NLRP3 inflammasome inhibitory activity and cytotoxicity. The major metabolite had 170-fold less inhibitory activity (IC50-1238 nM) than MCC950 (IC50-7.5 nM). Interestingly, one regioisomer had shown nanomolar inhibitory activity (IC50-232 nM). However, no evidence of cytotoxicity was observed with any of these synthesized compounds when tested in human embryonic kidney 293 cells (HEK293) and human liver hepatocellular carcinoma G2 cells (HepG2). These key findings give an insight into the SAR of the hexahydroindacene moiety of MCC950 and reveal a metabolic soft spot which could be blocked by chemical modification.

Keywords: Cytochrome P450, inflammasome, MCC950, metabolite, microsome, NLRP3

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Authors: Yihenew Simegniew Birhan, Hsieh Chih Tsai

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The recent advancements in synthetic chemistry and nanotechnology fostered the development of different nanocarriers for enhanced intracellular delivery of pharmaceutical agents to tumor cells. Polymeric micelles (PMs), characterized by small size, appreciable drug loading capacity (DLC), better accumulation in tumor tissue via enhanced permeability and retention (EPR) effect, and the ability to avoid detection and subsequent clearance by the mononuclear phagocyte (MNP) system, are convenient to improve the poor solubility, slow absorption and non-selective biodistribution of payloads embedded in their hydrophobic cores and hence, enhance the therapeutic efficacy of chemotherapeutic agents. Recently, redox-responsive polymeric micelles have gained significant attention for the delivery and controlled release of anticancer drugs in tumor cells. In this study, we synthesized redox-responsive diselenide bond containing amphiphilic polymer, Bi(mPEG-PLGA)-Se₂ from mPEG-PLGA, and 3,3'-diselanediyldipropanoic acid (DSeDPA) using DCC/DMAP as coupling agents. The successful synthesis of the copolymers was verified by different spectroscopic techniques. Above the critical micelle concentration, the amphiphilic copolymer, Bi(mPEG-PLGA)-Se₂, self-assembled into stable micelles. The DLS data indicated that the hydrodynamic diameter of the micelles (123.9 ± 0.85 nm) was suitable for extravasation into the tumor cells through the EPR effect. The drug loading content (DLC) and encapsulation efficiency (EE) of DOX-loaded micelles were found to be 6.61 wt% and 54.9%, respectively. The DOX-loaded micelles showed initial burst release accompanied by sustained release trend where 73.94% and 69.54% of encapsulated DOX was released upon treatment with 6mM GSH and 0.1% H₂O₂, respectively. The biocompatible nature of Bi(mPEG-PLGA)-Se₂ copolymer was confirmed by the cell viability study. In addition, the DOX-loaded micelles exhibited significant inhibition against HeLa cells (44.46%), at a maximum dose of 7.5 µg/mL. The fluorescent microscope images of HeLa cells treated with 3 µg/mL (equivalent DOX concentration) revealed efficient internalization and accumulation of DOX-loaded Bi(mPEG-PLGA)-Se₂ micelles in the cytosol of cancer cells. In conclusion, the intelligent, biocompatible, and the redox stimuli-responsive behavior of Bi(mPEG-PLGA)-Se₂ copolymer marked the potential applications of diselenide-linked mPEG-PLGA micelles for the delivery and on-demand release of chemotherapeutic agents in cancer cells.

Keywords: anticancer drug delivery, diselenide bond, polymeric micelles, redox-responsive

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Authors: Naomi Sakamoto, Eisuke Fukuma, Mika Nashimoto, Yoshitomo Koshida

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Background: Selective localization of the metastatic lymph node with clip and removal of clipped nodes with sentinel lymph node (SLN), known as targeted axillary dissection (TAD), reduced false-negative rates (FNR) of SLN biopsy (SLNB) after neoadjuvant chemotherapy (NAC). For the patients who achieved nodal pathologic complete response (pCR), accurate staging of axilla by TAD lead to omit axillary lymph node dissection (ALND), decreasing postoperative arm morbidity without a negative effect on overall survival. This study aimed to investigate the ultrasound (US) identification rate and success removal rate of two kinds of ultrasound-visible clips placed in metastatic lymph nodes during TAD procedure. Methods: This prospective study was conducted using patients with clinically T1-3, N1, 2, M0 breast cancer undergoing NAC followed by surgery. A US-visible clip was placed in the suspicious lymph node under US guidance before neoadjuvant chemotherapy. Before surgery, US examination was performed to evaluate the detection rate of clipped node. During the surgery, the clipped node was removed using several localization techniques, including hook-wire localization, dye-injection, or fluorescence technique, followed by a dual-technique SLNB and resection of palpable nodes if present. For the fluorescence technique, after injection of 0.1-0.2 mL of indocyanine green dye (ICG) into the clipped node, ICG fluorescent imaging was performed using the Photodynamic Eye infrared camera (Hamamatsu Photonics k. k., Shizuoka, Japan). For the dye injection method, 0.1-0.2 mL of pyoktanin blue dye was injected into the clipped node. Results: A total of 29 patients were enrolled. Hydromark™ breast biopsy site markers (Hydromark, T3 shape; Devicor Medical Japan, Tokyo, Japan) was used in 15patients, whereas a UltraCor™ Twirl™ breast marker (Twirl; C.R. Bard, Inc, NJ, USA) was placed in 14 patients. US identified the clipped node marked with the UltraCore Twirl in 100% (14/14) and with the Hydromark in 93.3% (14/15, p = ns). Success removal of clipped node marked with the UltraCore Twirl was achieved in 100% (14/14), whereas the node marked with the Hydromark was removed in 80% (12/15) (p = ns). Conclusions: The ultrasound identification rate differed between the two types of ultrasound-visible clips, which also affected the success removal rate of clipped nodes. Labelling the positive node with a US-highly-visible clip allowed successful TAD.

Keywords: breast cancer, neoadjuvant chemotherapy, targeted axillary dissection, breast tissue marker, clip

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Authors: Peter Clutterbuck, Terry Rowlands, Owen Seamons

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In this paper we describe one critical research program within a complex, ongoing multi-year project (2010 to 2014 inclusive) with the overall goal to improve the learning outcomes for first year undergraduate commerce/business students within an Information Systems (IS) subject with very large enrolment. The single research program described in this paper is the analysis of student attitudes and decision making in relation to the availability of formative assessment feedback via Web-based real time conferencing and document exchange software (Adobe Connect). The formative assessment feedback between teaching staff and students is in respect of an authentic problem-based, team-completed assignment. The analysis of student attitudes and decision making is investigated via both qualitative (firstly) and quantitative (secondly) application of the Theory of Planned Behavior (TPB) with a two statistically-significant and separate trial samples of the enrolled students. The initial qualitative TPB investigation revealed that perceived self-efficacy, improved time-management, and lecturer-student relationship building were the major factors in shaping an overall favorable student attitude to online feedback, whilst some students expressed valid concerns with perceived control limitations identified within the online feedback protocols. The subsequent quantitative TPB investigation then confirmed that attitude towards usage, subjective norms surrounding usage, and perceived behavioral control of usage were all significant in shaping student intention to use the online feedback protocol, with these three variables explaining 63 percent of the variance in the behavioral intention to use the online feedback protocol. The identification in this research of perceived behavioral control as a significant determinant in student usage of a specific technology component within a virtual learning environment (VLE) suggests that VLEs could now be viewed not as a single, atomic entity, but as a spectrum of technology offerings ranging from the mature and simple (e.g., email, Web downloads) to the cutting-edge and challenging (e.g., Web conferencing and real-time document exchange). That is, that all VLEs should not be considered the same. The results of this research suggest that tertiary students have the technological sophistication to assess a VLE in this more selective manner.

Keywords: formative assessment feedback, virtual learning environment, theory of planned behavior, perceived behavioral control

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Authors: Binbin Chen, Dennis Y. C. Leung

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Aluminium (Al) -air cell holds a high volumetric capacity density of 8.05 Ah cm-3, benefit from the trivalence of Al ions. Additional benefits of Al-air cell are low price and environmental friendliness. Furthermore, the Al energy conversion process is characterized of 100% recyclability in theory. Along with a large base of raw material reserve, Al attracts considerable attentions as a promising material to be integrated within the global energy system. However, despite the early successful applications in military services, several problems exist that prevent the Al-air cells from widely civilian use. The most serious issue is the parasitic corrosion of Al when contacts with electrolyte. To overcome this problem, super-pure Al alloyed with various traces of metal elements are used to increase the corrosion resistance. Nevertheless, high-purity Al alloys are costly and require high energy consumption during production process. An alternative approach is to add inexpensive inhibitors directly into the electrolyte. However, such additives would increase the internal ohmic resistance and hamper the cell performance. So far these methods have not provided satisfactory solutions for the problem within Al-air cells. For the operation of alkaline Al-air cell, there are still other minor problems. One of them is the formation of aluminium hydroxide in the electrolyte. This process decreases ionic conductivity of electrolyte. Another one is the carbonation process within the gas diffusion layer of cathode, blocking the porosity of gas diffusion. Both these would hinder the performance of cells. The present work optimizes the above problems by building an Al-air cell operation system, consisting of four components. A top electrolyte tank containing fresh electrolyte is located at a high level, so that it can drive the electrolyte flow by gravity force. A mechanical rechargeable Al-air cell is fabricated with low-cost materials including low grade Al, carbon paper, and PMMA plates. An electrolyte waste tank with elaborate channel is designed to separate the hydrogen generated from the corrosion, which would be collected by gas collection device. In the first section of the research work, we investigated the performance of the mechanical rechargeable Al-air cell with a constant flow rate of electrolyte, to ensure the repeatability experiments. Then the whole system was assembled together and the feasibility of operating was demonstrated. During experiment, pure hydrogen is collected by collection device, which holds potential for various applications. By collecting this by-product, high utilization efficiency of aluminum is achieved. Considering both electricity and hydrogen generated, an overall utilization efficiency of around 90 % or even higher under different working voltages are achieved. Fluidic electrolyte could remove aluminum hydroxide precipitate and solve the electrolyte deterioration problem. This operation system provides a low-cost strategy for harvesting energy from the abundant secondary Al. The system could also be applied into other metal-air cells and is suitable for emergency power supply, power plant and other applications. The low cost feature implies great potential for commercialization. Further optimization, such as scaling up and optimization of fabrication, will help to refine the technology into practical market offerings.

Keywords: aluminium-air cell, high efficiency, hydrogen, mechanical recharge

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Authors: Huayuan Lu, Chunfang Yang, Ma Zhu, Baojun Qi, Yaqiong Qiao, Jiangqian Xu

Abstract:

Image geolocalization has great application prospects in fields such as autonomous driving and virtual/augmented reality. In practical application scenarios, the size of the image to be located is not fixed; it is impractical to train different networks for all possible sizes. When its size does not match the size of the input of the descriptor extraction model, existing image geolocalization methods usually directly scale or crop the image in some common ways. This will result in the loss of some information important to the geolocalization task, thus affecting the performance of the image geolocalization method. For example, excessive down-sampling can lead to blurred building contour, and inappropriate cropping can lead to the loss of key semantic elements, resulting in incorrect geolocation results. To address this problem, this paper designs a learnable image resizer and proposes an arbitrary-sized image geolocation method. (1) The designed learnable image resizer employs the self-attention mechanism to enhance the geometric features of the resized image. Firstly, it applies bilinear interpolation to the input image and its feature maps to obtain the initial resized image and the resized feature maps. Then, SKNet (selective kernel net) is used to approximate the best receptive field, thus keeping the geometric shapes as the original image. And SENet (squeeze and extraction net) is used to automatically select the feature maps with strong contour information, enhancing the geometric features. Finally, the enhanced geometric features are fused with the initial resized image, to obtain the final resized images. (2) The proposed image geolocalization method embeds the above image resizer as a fronting layer of the descriptor extraction network. It not only enables the network to be compatible with arbitrary-sized input images but also enhances the geometric features that are crucial to the image geolocalization task. Moreover, the triplet attention mechanism is added after the first convolutional layer of the backbone network to optimize the utilization of geometric elements extracted by the first convolutional layer. Finally, the local features extracted by the backbone network are aggregated to form image descriptors for image geolocalization. The proposed method was evaluated on several mainstream datasets, such as Pittsburgh30K, Tokyo24/7, and Places365. The results show that the proposed method has excellent size compatibility and compares favorably to recently mainstream geolocalization methods.

Keywords: image geolocalization, self-attention mechanism, image resizer, geometric feature

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Authors: Jafar S. Noori, Jan Romano-deGea, Maria Dimaki, John Mortensen, Winnie E. Svendsen

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Pesticides have been intensively used in agriculture to control weeds, insects, fungi, and pest. One of the most commonly used pesticides is glyphosate. Glyphosate has the ability to attach to the soil colloids and degraded by the soil microorganisms. As glyphosate led to the appearance of resistant species, the pesticide was used more intensively. As a consequence of the heavy use of glyphosate, residues of this compound are increasingly observed in food and water. Recent studies reported a direct link between glyphosate and chronic effects such as teratogenic, tumorigenic and hepatorenal effects although the exposure was below the lowest regulatory limit. Today, pesticides are detected in water by complicated and costly manual procedures conducted by highly skilled personnel. It can take up to several days to get an answer regarding the pesticide content in water. An alternative to this demanding procedure is offered by electrochemical measuring techniques. Electrochemistry is an emerging technology that has the potential of identifying and quantifying several compounds in few minutes. It is currently not possible to detect glyphosate directly in water samples, and intensive research is underway to enable direct selective and quantitative detection of glyphosate in water. This study focuses on developing and modifying a sensor chip that has the ability to selectively measure glyphosate and minimize the signal interference from other compounds. The sensor is a silicon-based chip that is fabricated in a cleanroom facility with dimensions of 10×20 mm. The chip is comprised of a three-electrode configuration. The deposited electrodes consist of a 20 nm layer chromium and 200 nm gold. The working electrode is 4 mm in diameter. The working electrodes are modified by creating molecularly imprinted polymers (MIP) using electrodeposition technique that allows the chip to selectively measure glyphosate at low concentrations. The modification included using gold nanoparticles with a diameter of 10 nm functionalized with 4-aminothiophenol. This configuration allows the nanoparticles to bind to the working electrode surface and create the template for the glyphosate. The chip was modified using electrodeposition technique. An initial potential for the identification of glyphosate was estimated to be around -0.2 V. The developed sensor was used on 6 different concentrations and it was able to detect glyphosate down to 0.5 mgL⁻¹. This value is below the accepted pesticide limit of 0.7 mgL⁻¹ set by the US regulation. The current focus is to optimize the functionalizing procedure in order to achieve glyphosate detection at the EU regulatory limit of 0.1 µgL⁻¹. To the best of our knowledge, this is the first attempt to modify miniaturized sensor electrodes with functionalized nanoparticles for glyphosate detection.

Keywords: pesticides, glyphosate, rapid, detection, modified, sensor

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Authors: A. Abdi, A. Abbasi Daloee, A. Barari

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Aim: The adaptations that occur in human body after doing exercises training are a factor to help healthy people stay away from certain diseases. One of the main adaptations is a change in blood circulation, especially in vessels. The increase of capillary density is dependent on the balance between angiogenic and angiostatic factors. Most studies show that the changes made to angiogenic developmental factors resulted from physical exercises indicate the low level of stimulators compared with inhibitors. It is believed that the plasma level of VEGF-A, the important angiogenic factor, is reduced after physical exercise. Findings indicate that the extract of crataegus plant reduces the platelet-derived growth factor receptor (PDGFR) autophosphorylation in human's fibroblast. More importantly, crataegus (1 to 100 mg in liter) clearly leads to the inhibition of PDGFR autophosphorylation in vascular smooth muscle cells (VSMCs). Angiogenesis is a process that can be classified into physiological and pathophysiological forms. collagen XVIII is a part of extracellular protein and heparan sulfate proteoglycans in vascular epithelial and endothelial basement membrane cause the release of endostatin from noncollagenous collagen XVIII. Endostatin inhibits the growth of endothelial cells, inhibits angiogenesis, weakens different types of cancer, and the growth of tumors. The purpose of the current study was to investigate the effect of intensive aerobic running with or without aqueous extraction of black Crataegus elbursensis on Collagen XVIII in male rats. Design: Thirty-two Wistar male rats (4-6 weeks old, 125-135 gr weight) were acquired from the Pasteur's Institute (Amol, Mazandaran), and randomly assigned into control (n = 16) and training (n = 16) groups. Rats were further divided into saline-control (SC) (n=8), saline-training (ST) (n=8), crataegus pentaegyna extraction -control (CPEC) (n=8), and crataegus pentaegyna extraction - training (CPET) (n=8). The control (SC and CPEC) groups remained sedentary; whereas the training groups underwent a high running exercise program. plasma were excised and immediately frozen in liquid nitrogen. Statistical analysis was performed using a one way analysis of variance and Tukey test. Significance was accepted at P = 0.05. Results: The results show that aerobic exercise group had the highest concentration collagen XVIII compared to other groups and then respectively black crataegus, training-crataegus and control groups. Conclusion: In general, researchers in this study concluded that the increase of collagen XVIII (albeit insignificant) as a result of physical activity and consumption of black crataegus extract could possibly serve as a regional inhibitor of angiogenesis and another evidence for the anti-cancer effects of physical activities. Since the research has not managed in this study to measure the amount of plasma endostatin, it is suggested that both indices are measured with important angiogenic factors so that we can have a more accurate interpretation of changes to angiogenic and angiostatic factors resulted from physical exercises.

Keywords: aerobic running, Crataegus elbursensis, Collagen XVIII

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Authors: Hsiang-Ru Lin

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Cholesterol plays an essential role in the regulation of the progression of numerous important diseases including atherosclerosis and Alzheimer disease so the generation of suitable cholesterol-lowering reagents is urgent to develop. Liver X receptor (LXR) is a ligand-activated transcription factor whose natural ligands are cholesterols, oxysterols and glucose. Once being activated, LXR can transactivate the transcription action of various genes including CYP7A1, ABCA1, and SREBP1c, involved in the lipid metabolism, glucose metabolism and inflammatory pathway. Essentially, the upregulation of ABCA1 facilitates cholesterol efflux from the cells and attenuates the production of beta-amyloid (ABeta) 42 in brain so LXR is a promising target to develop the cholesterol-lowering reagents and preventative treatment of Alzheimer disease. Engelhardia roxburghiana is a deciduous tree growing in India, China, and Taiwan. However, its chemical composition is only reported to exhibit antitubercular and anti-inflammatory effects. In this study, four compounds, engelheptanoxides A, C, engelhardiol A, and B isolated from the root of Engelhardia roxburghiana were evaluated for their agonistic activity against LXR by the transient transfection reporter assays in the HepG2 cells. Furthermore, their interactive modes with LXR ligand binding pocket were generated by molecular modeling programs. By using the cell-based biological assays, engelheptanoxides A, C, engelhardiol A, and B showing no cytotoxic effect against the proliferation of HepG2 cells, exerted obvious LXR agonistic effects with similar activity as T0901317, a novel synthetic LXR agonist. Further modeling studies including docking and SAR (structure-activity relationship) showed that these compounds can locate in LXR ligand binding pocket in the similar manner as T0901317. Thus, LXR is one of nuclear receptors targeted by pharmaceutical industry for developing treatments of Alzheimer and atherosclerosis diseases. Importantly, the cell-based assays, together with molecular modeling studies suggesting a plausible binding mode, demonstrate that engelheptanoxides A, C, engelhardiol A, and B function as LXR agonists. This is the first report to demonstrate that the extract of Engelhardia roxburghiana contains LXR agonists. As such, these active components of Engelhardia roxburghiana or subsequent analogs may show important therapeutic effects through selective modulation of the LXR pathway.

Keywords: Liver X receptor (LXR), Engelhardia roxburghiana, CYP7A1, ABCA1, SREBP1c, HepG2 cells

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Authors: Lachin Mikjtarnejad, Mohsen Farzaneh

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Various microbes, such as fungi and bacteria species, are naturally found in the fruit microbiota, and some of them act as a pathogen and result in fruit rot. Among non-pathogenic microbes, yeasts (single-celled microorganisms belonging to the fungi kingdom) can colonize fruit tissues and interact with them without causing any damage to them. Although yeasts are part of the plant microbiota, there is little information about their interactions with plants in comparison with bacteria and filamentous fungi. According to several existing studies, some yeasts can colonize different plant species and have the biological control ability to suppress some of the plant pathogens. It means those specific yeast-colonized plants are more resistant to some plant pathogens. The major objective of the present investigation is to isolate yeast strains from apple fruit and screen their ability to control Penicillium expansum, the causal agent of blue mold of fruits. In the present study, psychrotrophic and epiphytic yeasts were isolated from apple fruits that were stored at low temperatures (0–1°C). Totally, 42 yeast isolates were obtained and identified by molecular analysis based on genomic sequences of the D1/D2 and ITS1/ITS4 regions of their rDNA. All isolated yeasts were primarily screened by' in vitro dual culture assay against P. expansum by measuring the fungus' relative growth inhibition after 10 days of incubation. The results showed that the mycelial growth of P. expansum was reduced between 41–53% when challenged by promising yeast strains. The isolates with the strongest antagonistic activity belonged to Metschnikowia pulcherrima A13, Rhodotorula mucilaginosa A41, Leucosporidium Scottii A26, Aureobasidium pullulans A19, Pichia guilliermondii A32, Cryptococcus flavescents A25, and Pichia kluyveri A40. The results of seven superior isolates to inhibit blue mold decay on fruit showed that isolates A. pullulans A19, L. scottii A26, and Pi. guilliermondii A32 could significantly reduce the fruit rot and decay with 26 mm, 22 mm and 20 mm zone diameter, respectively, compared to the control sample with 43 mm. Our results show Pi. guilliermondii strain A13 was the most effective yeast isolates in inhibiting P. expansum on apple fruits. In addition, various biological control mechanisms of promising biological isolates against blue mold have been evaluated to date, including competition for nutrients and space, production of volatile metabolites, reduction of spore germination, production of siderophores and production of extracellular lytic enzymes such as chitinase and β-1,3-glucanase. However, the competition for nutrients and the ability to inhibit P. expansum spore growth have been introduced as the prevailing mechanisms among them. Accordingly, in our study, isolates A13, A41, A40, A25, A32, A19 and A26 inhibited the germination of P. expansum, whereas isolates A13 and A19 were the strongest inhibitors of P. expansum mycelia growth, causing 89.13% and 81.75 % reduction in the mycelial surface, respectively. All the promising isolates produced chitinase and β-1,3-glucanase after 3, 5 and 7 days of cultivation. Finally, based on our findings, we are proposing that, Pi. guilliermondiias as an effective biocontrol agent and alternative to chemical fungicides to control the blue mold of apple fruit.

Keywords: yeast, yeast enzymes, biocontrol, post harvest diseases

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Authors: Hernando Santamaría-García, Sandra Báez, Pablo Reyes, José Santamaría-García, Diana Matallana, Adolfo García, Agustín Ibañez

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The study of moral emotions (i.e., Schadenfreude and envy) is critical to understand the ecological complexity of everyday interactions between cognitive, affective, and social cognition processes. Most previous studies in this area have used correlational imaging techniques and framed Schadenfreude and envy as monolithic domains. Here, we profit from a relevant neurodegeneration model to disentangle the brain regions engaged in three dimensions of Schadenfreude and envy: deservingness, morality, and legality. We tested 20 patients with behavioral variant frontotemporal dementia (bvFTD), 24 patients with Alzheimer’s disease (AD), as a contrastive neurodegeneration model, and 20 healthy controls on a novel task highlighting each of these dimensions in scenarios eliciting Schadenfreude and envy. Compared with the AD and control groups, bvFTD patients obtained significantly higher scores on all dimensions for both emotions. Interestingly, the legal dimension for both envy and Schadenfreude elicited higher emotional scores than the deservingness and moral dimensions. Furthermore, correlational analyses in bvFTD showed that higher envy and Schadenfreude scores were associated with greater deficits in social cognition, inhibitory control, and behavior. Brain anatomy findings (restricted to bvFTD and controls) confirmed differences in how these groups process each dimension. Schadenfreude was associated with the ventral striatum in all subjects. Also, in bvFTD patients, increased Schadenfreude across dimensions was negatively correlated with regions supporting social-value rewards, mentalizing, and social cognition (frontal pole, temporal pole, angular gyrus and precuneus). In all subjects, all dimensions of envy positively correlated with the volume of the anterior cingulate cortex, a region involved in processing unfair social comparisons. By contrast, in bvFTD patients, the intensified experience of envy across all dimensions was negatively correlated with a set of areas subserving social cognition, including the prefrontal cortex, the parahippocampus, and the amygdala. Together, the present results provide the first lesion-based evidence for the multidimensional nature of the emotional experiences of envy and Schadenfreude. Moreover, this is the first demonstration of a selective exacerbation of envy and Schadenfreude in bvFTD patients, probably triggered by atrophy to social cognition networks. Our results offer new insights into the mechanisms subserving complex emotions and moral cognition in neurodegeneration, paving the way for groundbreaking research on their interaction with other cognitive, social, and emotional processes.

Keywords: social cognition, moral emotions, neuroimaging, frontotemporal dementia

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Authors: Ivette Gonzalez-Rivera, Diana B. Paz-Trejo, Oscar Galicia-Castillo, David N. Velazquez-Martinez, Hugo Sanchez-Castillo

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Prolonged exposure to stress can cause disorders related with dysfunction in the prefrontal cortex such as generalized anxiety and depression. These disorders involve alterations in neurotransmitter systems; the serotonergic system—a target of the drugs that are commonly used as a treatment to these disorders—is one of them. Recent studies suggest that 5-HT1A receptors play a pivotal role in the serotonergic system regulation and in stress responses. In the same way, there is increasing evidence that astrocytes are involved in the pathophysiology of stress. The aim of this study was to examine the effects of 8-OH-DPAT, a selective agonist of 5-HT1A receptors, in the behavioral signs of anxiety and anhedonia as well as in the number of astrocytes in the medial prefrontal cortex (mPFC) after exposure to chronic stress. They used 50 male Wistar rats of 250-350 grams housed in standard laboratory conditions and treated in accordance with the ethical standards of use and care of laboratory animals. A protocol of chronic unpredictable stress was used for 10 consecutive days during which the presentation of stressors such as motion restriction, water deprivation, wet bed, among others, were used. 40 rats were subjected to the stress protocol and then were divided into 4 groups of 10 rats each, which were administered 8-OH-DPAT (Tocris, USA) intraperitoneally with saline as vehicle in doses 0.0, 0.3, 1.0 and 2.0 mg/kg respectively. Another 10 rats were not subjected to the stress protocol or the drug. Subsequently, all the rats were measured in an open field test, a forced swimming test, sucrose consume, and a cero maze test. At the end of this procedure, the animals were sacrificed, the brain was removed and the tissue of the mPFC (Bregma: 4.20, 3.70, 2.70, 2.20) was processed in immunofluorescence staining for astrocytes (Anti-GFAP antibody - astrocyte maker, ABCAM). Statistically significant differences were found in the behavioral tests of all groups, showing that the stress group with saline administration had more indicators of anxiety and anhedonia than the control group and the groups with administration of 8-OH-DPAT. Also, a dose dependent effect of 8-OH-DPAT was found on the number of astrocytes in the mPFC. The results show that 8-OH-DPAT can modulate the effect of stress in both behavioral and anatomical level. Also they indicate that 5-HT1A receptors and astrocytes play an important role in the stress response and may modulate the therapeutic effect of serotonergic drugs, so they should be explored as a fundamental part in the treatment of symptoms of stress and in the understanding of the mechanisms of stress responses.

Keywords: anxiety, prefrontal cortex, serotonergic system, stress

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Authors: Matthew E. Potter, Daniel J. Stewart, Lindsay M. Armstrong, Pier J. A. Sazio, Robert R. Raja

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Rising CO₂ levels in the atmosphere means that CO₂ is a highly desirable feedstock. This requires specific catalysts to be designed to activate this inert molecule, combining a catalytic site tailored for CO₂ transformations with a support that can readily adsorb CO₂. Metal organic frameworks (MOFs) are regularly used as CO₂ sorbents. The organic nature of the linker molecules, connecting the metal nodes, offers many post-synthesis modifications to introduce catalytic active sites into the frameworks. However, the metal nodes may be coordinatively unsaturated, allowing them to bind to organic moieties. Imidazoles have shown promise catalyzing the formation of cyclic carbonates from epoxides with CO₂. Typically, this synthesis route employs toxic reagents such as phosgene, liberating HCl. Therefore an alternative route with CO₂ is highly appealing. In this work we design active sites for CO₂ activation, by tethering substituted-imidazole organocatalytic species to the available Cr3+ metal nodes of a Cr-MIL-101 MOF, for the first time, to create a tailored species for carbon capture utilization applications. Our tailored design strategy combining a CO₂ sorbent, Cr-MIL-101, with an anchored imidazole results in a highly active and selective multifunctional catalyst, achieving turnover frequencies of over 750 hr-1. These findings demonstrate the synergy between the MOF framework and imidazoles for CO₂ utilization applications. Further, the effect of substrate variation has been explored yielding mechanistic insights into this process. Through characterization, we show that the structural and compositional integrity of the Cr-MIL-101 has been preserved on functionalizing the imidazoles. Further, we show the binding of the imidazoles to the Cr3+ metal nodes. This can be seen through our EPR study, where the distortion of the Cr3+ on binding to the imidazole shows the CO₂ binding site is close to the active imidazole. This has a synergistic effect, improving catalytic performance. We believe the combination of MOF support and organocatalyst allows many possibilities to generate new multifunctional catalysts for CO₂ utilisation. In conclusion, we have validated our design procedure, combining a known CO₂ sorbent, with an active imidazole species to create a unique tailored multifunctional catalyst for CO₂ utilization. This species achieves high activity and selectivity for the formation of cyclic carbonates and offers a sustainable alternative to traditional synthesis methods. This work represents a unique design strategy for CO₂ utilization while offering exciting possibilities for further work in characterization, computational modelling, and post-synthesis modification.

Keywords: carbonate, catalysis, MOF, utilisation

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Authors: Y. Teterin, S. Suleymanova, I. Dmitriev, P. Yartcev

Abstract:

Introduction: One of the most common complications after pancreas transplantation are pancreatic fluid collections (PFCs), which are often complicated not only by infection and subsequent disfunction of the pancreatoduodenal graft (PDG), but also with a rather high mortality rate of recipients. Drainage is not always effective and often requires repeated open surgical interventions, which worsens the outcome of the surgery. Percutaneous drainage of PFCs combined with endoscopic stenting of the main pancreatic duct of the pancreatoduodenal graft (MPDPDG) showed high efficiency in the treatment of PFCs. Aims & Methods: From 01.01.2012 to 31.12.2021 at the Sklifosovsky Research Institute for Emergency Medicine were performed 64 transplantations of PDG. In 11 cases (17.2%), the early postoperative period was complicated by the formation of PFCs. Of these, 7 patients underwent percutaneous drainage of pancreonecrosis with high efficiency and did not required additional methods of treatment. In the remaining 4 patients, drainage was ineffective and was an indication for endoscopic stenting of the MPDPDG. They were the ones who made up the study group. Among them were 3 men and 1 woman. The mean age of the patients was 36,4 years.PFCs in these patients formed on days 1, 12, 18, and 47 after PDG transplantation. We used a gastroscope to stent the MPDPDG, due to anatomical features of the location of the duodenoduodenal anastomosis after PDG transplantation. Through the endoscope channel was performed selective catheterization of the MPDPDG, using a catheter and a guidewire, followed by its contrasting with a water-soluble contrast agent. Due to the extravasation of the contrast, was determined the localization of the defect in the PDG duct system. After that, a plastic pancreatic stent with a diameter of 7 Fr. and a length of 7 cm. was installed along guidewire. The stent was installed in such a way that its proximal edge completely covered the defect zone, and the distal one was determined in the intestinal lumen. Results: In all patients PDG pancreaticography revealed extravasation of a contrast in the area of the isthmus and body of the pancreas, which required stenting of the MPDPDG. In 1 (25%) case, the patient had a dislocation of the stent into the intestinal lumen (III degree according to Clavien-Dindo (2009)). This patient underwent repeated endoscopic stenting of the MPDPDG. On average 23 days after endoscopic stenting of the MPDPDG, the drainage tubes were removed and after approximately 40 days all patients were discharged in a satisfactory condition with follow-up endocrinologist and surgeon consultation. Pancreatic stents were removed after 6 months ± 7 days. Conclusion: Endoscopic stenting of the main pancreatic duct of the donor pancreas is by far the most highly effective and minimally invasive method in the treatment of PFCs after transplantation of the pancreatoduodenal complex.

Keywords: pancreas transplantation, endoscopy surgery, diabetes, stenting, main pancreatic duct

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Authors: F. Ghani, T. S. O’Donovan

Abstract:

Today, the global solar thermal market is dominated by two collector types; the flat plate and evacuated tube collector. With regards to the number of installations worldwide, the evacuated tube collector is the dominant variant primarily due to the Chinese market but the flat plate collector dominates both the Australian and European markets. The market share of the evacuated tube collector is, however, growing in Australia due to a common belief that this collector type is ‘more efficient’ and, therefore, the better choice for hot water applications. In this study, we investigate this issue further to assess the validity of this statement. This was achieved by methodically comparing the performance and economics of several solar thermal systems comprising of; a low-performance flat plate collector, a high-performance flat collector, and an evacuated tube collector coupled with a storage tank and pump. All systems were simulated using the commercial software package Polysun for four climate zones in Australia to take into account different weather profiles in the study and subjected to a thermal load equivalent to a household comprising of four people. Our study revealed that the energy savings and payback periods varied significantly for systems operating under specific environmental conditions. Solar fractions ranged between 58 and 100 per cent, while payback periods range between 3.8 and 10.1 years. Although the evacuated tube collector was found to operate with a marginally higher thermal efficiency over the selective surface flat plate collector due to reduced ambient heat loss, the high-performance flat plate collector outperformed the evacuated tube collector on thermal yield. This result was obtained as the flat plate collector possesses a significantly higher absorber to gross collector area ratio over the evacuated tube collector. Furthermore, it was found for Australian regions operating with a high average solar radiation intensity and ambient temperature, the lower performance collector is the preferred choice due to favorable economics and reduced stagnation temperature. Our study has provided additional insight into the thermal performance and economics of the two prevalent solar thermal collectors currently available. A computational investigation has been carried out specifically for the Australian climate due to its geographic size and significant variation in weather. For domestic hot water applications were fluid temperatures between 50 and 60 degrees Celsius are sought, the flat plate collector is both technically and economically favorable over the evacuated tube collector. This research will be useful to system design engineers, solar thermal manufacturers, and those involved in policy to encourage the implementation of solar thermal systems into the hot water market.

Keywords: solar thermal, energy analysis, flat plate, evacuated tube, collector performance

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Authors: Zohar Manber, Ran Elkon

Abstract:

Accumulation of somatic mutations (SMs) in the genome is a major driving force of cancer development. Most SMs in the tumor's genome are functionally neutral; however, some cause damage to critical processes and provide the tumor with a selective growth advantage (termed cancer driver mutations). Current research on functional significance of SMs is mainly focused on finding alterations in protein coding sequences. However, the exome comprises only 3% of the human genome, and thus, SMs in the noncoding genome significantly outnumber those that map to protein-coding regions. Although our understanding of noncoding driver SMs is very rudimentary, it is likely that disruption of regulatory elements in the genome is an important, yet largely underexplored mechanism by which somatic mutations contribute to cancer development. The expression of most human genes is controlled by multiple enhancers, and therefore, it is conceivable that regulatory SMs are distributed across different enhancers of the same target gene. Yet, to date, most statistical searches for regulatory SMs have considered each regulatory element individually, which may reduce statistical power. The first challenge in considering the cumulative activity of all the enhancers of a gene as a single unit is to map enhancers to their target promoters. Such mapping defines for each gene its set of regulating enhancers (termed "set of regulatory elements" (SRE)). Considering multiple enhancers of each gene as one unit holds great promise for enhancing the identification of driver regulatory SMs. However, the success of this approach is greatly dependent on the availability of comprehensive and accurate enhancer-promoter (E-P) maps. To date, the discovery of driver regulatory SMs has been hindered by insufficient sample sizes and statistical analyses that often considered each regulatory element separately. In this study, we analyzed more than 2,500 whole-genome sequence (WGS) samples provided by The Cancer Genome Atlas (TCGA) and The International Cancer Genome Consortium (ICGC) in order to identify such driver regulatory SMs. Our analyses took into account the combinatorial aspect of gene regulation by considering all the enhancers that control the same target gene as one unit, based on E-P maps from three genomics resources. The identification of candidate driver noncoding SMs is based on their recurrence. We searched for SREs of genes that are "hotspots" for SMs (that is, they accumulate SMs at a significantly elevated rate). To test the statistical significance of recurrence of SMs within a gene's SRE, we used both global and local background mutation rates. Using this approach, we detected - in seven different cancer types - numerous "hotspots" for SMs. To support the functional significance of these recurrent noncoding SMs, we further examined their association with the expression level of their target gene (using gene expression data provided by the ICGC and TCGA for samples that were also analyzed by WGS).

Keywords: cancer genomics, enhancers, noncoding genome, regulatory elements

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Authors: Miroslava Cuperlovic-Culf, Lipu Wang, Ketty Boyle, Nadine Makley, Ian Burton, Anissa Belkaid, Mohamed Touaibia, Marc E. Surrette

Abstract:

Metabolic changes are one of the major factors in the development of a variety of diseases in various species. Metabolism of agricultural plants is altered the following infection with pathogens sometimes contributing to resistance. At the same time, pathogens use metabolites for infection and progression. In humans, metabolism is a hallmark of cancer development for example. Quantified metabolomics data combined with other omics or clinical data and analyzed using various unsupervised and supervised methods can lead to better diagnosis and prognosis. It can also provide information about resistance as well as contribute knowledge of compounds significant for disease progression or prevention. In this work, different methods for metabolomics quantification and analysis from Nuclear Magnetic Resonance (NMR) measurements that are used for investigation of disease development in wheat and human cells will be presented. One-dimensional 1H NMR spectra are used extensively for metabolic profiling due to their high reliability, wide range of applicability, speed, trivial sample preparation and low cost. This presentation will describe a new method for metabolite quantification from NMR data that combines alignment of spectra of standards to sample spectra followed by multivariate linear regression optimization of spectra of assigned metabolites to samples’ spectra. Several different alignment methods were tested and multivariate linear regression result has been compared with other quantification methods. Quantified metabolomics data can be analyzed in the variety of ways and we will present different clustering methods used for phenotype determination, network analysis providing knowledge about the relationships between metabolites through metabolic network as well as biomarker selection providing novel markers. These analysis methods have been utilized for the investigation of fusarium head blight resistance in wheat cultivars as well as analysis of the effect of estrogen receptor and carbonic anhydrase activation and inhibition on breast cancer cell metabolism. Metabolic changes in spikelet’s of wheat cultivars FL62R1, Stettler, MuchMore and Sumai3 following fusarium graminearum infection were explored. Extensive 1D 1H and 2D NMR measurements provided information for detailed metabolite assignment and quantification leading to possible metabolic markers discriminating resistance level in wheat subtypes. Quantification data is compared to results obtained using other published methods. Fusarium infection induced metabolic changes in different wheat varieties are discussed in the context of metabolic network and resistance. Quantitative metabolomics has been used for the investigation of the effect of targeted enzyme inhibition in cancer. In this work, the effect of 17 β -estradiol and ferulic acid on metabolism of ER+ breast cancer cells has been compared to their effect on ER- control cells. The effect of the inhibitors of carbonic anhydrase on the observed metabolic changes resulting from ER activation has also been determined. Metabolic profiles were studied using 1D and 2D metabolomic NMR experiments, combined with the identification and quantification of metabolites, and the annotation of the results is provided in the context of biochemical pathways.

Keywords: metabolic biomarkers, metabolic network, metabolomics, multivariate linear regression, NMR quantification, quantified metabolomics, spectral alignment

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