Search results for: selective serotonin reuptake inhibitors (SSRIs)

Authors: Michella Alnajjar, Frederic Christien, Krzysztof Wolski, Cedric Bosch

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Additive manufacturing (AM) has gained more interest in the past few years because it allows 3D parts often having a complex geometry to be directly fabricated, layer by layer according to a CAD model. One of the AM techniques is the selective laser melting (SLM) which is based on powder bed fusion. In this work, the corrosion resistance of 17-4 PH steel obtained by SLM is investigated. Wrought 17-4 PH steel is a martensitic precipitation hardenable stainless steel. It is widely used in a variety of applications such as aerospace, medical and food industries, due to its high strength and relatively good corrosion resistance. However, the combined findings of X-Ray diffraction and electron backscatter diffraction (EBSD) proved that SLM-ed 17-4 PH steel has a fully ferritic microstructure, more specifically δ ferrite. The microstructure consists of coarse ferritic grains elongated along the build direction, with a pronounced solidification crystallographic texture. These results were associated with the high cooling and heating rates experienced throughout the SLM process (10⁵-10⁶ K/s) that suppressed the austenite formation and produced a 'by-passing' phenomenon of this phase during the numerous thermal cycles. Furthermore, EDS measurements revealed a uniform distribution of elements without any dendritic structure. The extremely high cooling kinetics induced a diffusionless solidification, resulting in a homogeneous elemental composition. Consequently, the corrosion properties of this steel are altered from that of conventional ones. By using electrochemical means, it was found that SLM-ed 17-4 PH is more resistant to general corrosion than the wrought steel. However, the SLM-ed material exhibits metastable pitting due to its high porosity density. In addition, the hydrogen embrittlement of SLM-ed 17-4 PH steel is investigated, and a correlation between its behavior and the observed microstructure is made.

Keywords: corrosion resistance, 17-4 PH stainless steel, selective laser melting, hydrogen embrittlement

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Authors: Merve Akca

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Retrieval-induced forgetting (RIF) refers to the phenomenon that selective retrieval of some information impairs memory for related, but not previously retrieved information. Despite age differences in retrieval-induced forgetting regarding retrospective memory being documented, this research aimed to highlight age differences in RIF of the prospective memory tasks for the first time. By using retrieval-practice paradigm, this study comparatively examined RIF effects in retrospective memory and event-based prospective memory in young and old adults. In this experimental study, a mixed factorial design with age group (Young, Old) as a between-subject variable, and memory type (Prospective, Retrospective) and item type (Practiced, Non-practiced) as within-subject variables was employed. Retrieval-induced forgetting was observed in the retrospective but not in the prospective memory task. Therefore, the results indicated that selective retrieval of past events led to suppression of other related past events in both age groups but not the suppression of memory for future intentions.

Keywords: prospective memory, retrieval-induced forgetting, retrieval inhibition, retrospective memory

Procedia PDF Downloads 287

Authors: Aniket Kumar, Jacob Peedicayil

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Major depressive disorder (MDD) is a common and important psychiatric disorder. Several clinical features of MDD suggest an epigenetic basis for its pathogenesis. Since epigenetics (heritable changes in gene expression not involving changes in DNA sequence) may underlie the pathogenesis of MDD, epigenetic drugs such as DNA methyltransferase inhibitors (DNMTi) and histone deactylase inhibitors (HDACi) may be useful for treating MDD. The available literature indexed in Pubmed on preclinical drug trials of epigenetic drugs for the treatment of MDD was investigated. The search terms we used were ‘depression’ or ‘depressive’ and ‘HDACi’ or ‘DNMTi’. Among epigenetic drugs, it was found that there were 3 preclinical trials using HDACi and 3 using DNMTi for the treatment of MDD. All the trials were conducted on rodents (mice or rats). The animal models of depression that were used were: learned helplessness-induced animal model, forced swim test, open field test, and the tail suspension test. One study used a genetic rat model of depression (the Flinders Sensitive Line). The HDACi that were tested were: sodium butyrate, compound 60 (Cpd-60), and valproic acid. The DNMTi that were tested were: 5-azacytidine and decitabine. Among the three preclinical trials using HDACi, all showed an antidepressant effect in animal models of depression. Among the 3 preclinical trials using DNMTi also, all showed an antidepressant effect in animal models of depression. Thus, epigenetic drugs, namely, HDACi and DNMTi, may prove to be useful in the treatment of MDD and merit further investigation for the treatment of this disorder.

Keywords: DNA methylation, drug discovery, epigenetics, major depressive disorder

Procedia PDF Downloads 155

Authors: Srinivasa Reddy Mallampati, Chi-Hyeon Lee, Nguyen Thi Thanh Truc, Byeong-Kyu Lee

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In the present study, feasibility of the selective surface hydrophilization of polyvinyl chloride (PVC) by microwave treatment was evaluated to facilitate the separation from automotive shredder residue (ASR), by the froth flotation. The combination of 60 sec microwave treatment with PAC, a sharp and significant decrease about 16.5° contact angle of PVC was observed in ASR plastic compared with other plastics. The microwave treatment with the addition of PAC resulted in a synergetic effect for the froth flotation, which may be a result of the 90% selective separation of PVC from ASR plastics, with 82% purity. While, simple mixing with a nanometallic Ca/CaO/PO4 dispersion mixture immobilized 95-100% of heavy metals in ASR soil/residues. The quantity of heavy metals leached from thermal residues after treatment by nanometallic Ca/CaO/PO4 was lower than the Korean standard regulatory limit for hazardous waste landfills. Microwave treatment can be a simple and effective method for PVC separation from ASR plastics.

Keywords: automotive shredder residue, chlorinated plastics, hazardous waste, heavy metals, immobilization, separation

Procedia PDF Downloads 484

Authors: Lindsey Carruthers, Alexandra Willis, Rory MacLean

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Introduction: It has been proposed that distractibility, a key diagnostic criterion of Attention Deficit Hyperactivity Disorder (ADHD), may be associated with higher creativity levels in some individuals. Anecdotal and empirical evidence has shown that ADHD is therefore beneficial to creative problem-solving, and the generation of new ideas and products. Previous studies have only used one or two measures of attention, which is insufficient given that it is a complex cognitive process. The current study aimed to determine in which ways performance on creative problem-solving tasks and a range of attention tests may be related, and if performance differs between adults with and without ADHD. Methods: 150 adults, 47 males and 103 females (mean age=28.81 years, S.D.=12.05 years), were tested at Edinburgh Napier University. Of this set, 50 participants had ADHD, and 100 did not, forming the control group. Each participant completed seven attention tasks, assessing focussed, sustained, selective, and divided attention. Creative problem-solving was measured using divergent thinking tasks, which require multiple original solutions for one given problem. Two types of divergent thinking task were used: verbal (requires written responses) and figural (requires drawn responses). Each task is scored for idea originality, with higher scores indicating more creative responses. Correlational analyses were used to explore relationships between attention and creative problem-solving, and t-tests were used to study the between group differences. Results: The control group scored higher on originality for figural divergent thinking (t(148)= 3.187, p< .01), whereas the ADHD group had more original ideas for the verbal divergent thinking task (t(148)= -2.490, p < .05). Within the control group, figural divergent thinking scores were significantly related to both selective (r= -.295 to -.285, p < .01) and divided attention (r= .206 to .290, p < .05). Alternatively, within the ADHD group, both selective (r= -.390 to -.356, p < .05) and divided (r= .328 to .347, p < .05) attention are related to verbal divergent thinking. Conclusions: Selective and divided attention are both related to divergent thinking, however the performance patterns are different between each group, which may point to cognitive variance in the processing of these problems and how they are managed. The creative differences previously found between those with and without ADHD may be dependent on task type, which to the author’s knowledge, has not been distinguished previously. It appears that ADHD does not specifically lead to higher creativity, but may provide explanation for creative differences when compared to those without the disorder.

Keywords: ADHD, attention, creativity, problem-solving

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Authors: Hasan Al Bashar Abul Ulayee, AKM Saifun Nabi, MD Mesbah-Ul-Awal

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Alert system for disaster management is common now a day and can play a vital role reducing devastation and saves lives and costs. An alert in right time can save thousands of human life, help to take shelter, manage other assets including live stocks and above all, a right time alert will help to take preparation to face and early recovery of the situation. In a country like Bangladesh where populations is more than 170 million and always facing different types of natural calamities and disasters, an early right time alert is very effective and implementation of alert system is challenging. The challenge comes from the time constraint of alerting the huge number of population. The other method of existing disaster management pre alert is traditional, sequential and non-selective so efficiency is not good enough. This paper describes a way by which alert can be provided to maximum number of people within the short time bound using parallel processing as well as random selection of selective target audience.

Keywords: alert system, Bangladesh, disaster management, parallel processing, SMS

Procedia PDF Downloads 443

Authors: Tiziana Biasutti, Daniela Rigamonti, Lorenzo Palmiotti, Adelaide Nespoli, Paolo Bettini

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Aerospace industry is based on the continuous development of new technologies and solutions that allows constant improvement of the systems. Shape Memory Alloys are smart materials that can be used as dampers due to their pseudoelastic effect. The purpose of the research was to design a passive damper in Nitinol, manufactured by Selective Laser Melting, for space applications to reduce vibration between different structural parts in space structures. The powder is NiTi (50.2 at.% of Ni). The structure manufactured by additive technology allows us to eliminate the presence of joint and moving parts and to have a compact solution with high structural strength. The designed dampers had single or double cell structures with three different internal angles (30°, 45° and 60°). This particular shape has damping properties also without the pseudoelastic effect. For this reason, the geometries were reproduced in different materials, SS316L and Ti6Al4V, to test the geometry loss factor. The mechanical performances of these specimens were compared to the ones of NiTi structures, pointing out good damping properties of the designed structure and the highest performances of the NiTi pseudoelastic effect. The NiTi damper was mechanically characterized by static and dynamic tests and with DSC and microscope observations. The experimental results were verified with numerical models and with some scaled steel specimens in which optical fibers were embedded. The realized structure presented good mechanical and damping properties. It was observed that the loss factor and the dissipated energy increased with the angles of the cells.

Keywords: additive manufacturing, damper, nitinol, pseudo elastic effect, selective laser melting, shape memory alloys

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Authors: Nadia El Alami El Hassani, Soukaina Motia, Benachir Bouchikhi, Nezha El Bari

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Doxycycline (DXy) is a cycline antibiotic, most frequently prescribed to treat bacterial infections in veterinary medicine. However, its broad antimicrobial activity and low cost, lead to an intensive use, which can seriously affect human health. Therefore, its spread in the food products has to be monitored. The scope of this work was to synthetize a sensitive and very selective molecularly imprinted polymer (MIP) for DXy detection in honey samples. Firstly, the synthesis of this biosensor was performed by casting a layer of carboxylate polyvinyl chloride (PVC-COOH) on the working surface of a gold screen-printed electrode (Au-SPE) in order to bind covalently the analyte under mild conditions. Secondly, DXy as a template molecule was bounded to the activated carboxylic groups, and the formation of MIP was performed by a biocompatible polymer by the mean of polyacrylamide matrix. Then, DXy was detected by measurements of differential pulse voltammetry (DPV). A non-imprinted polymer (NIP) prepared in the same conditions and without the use of template molecule was also performed. We have noticed that the elaborated biosensor exhibits a high sensitivity and a linear behavior between the regenerated current and the logarithmic concentrations of DXy from 0.1 pg.mL⁻¹ to 1000 pg.mL⁻¹. This technic was successfully applied to determine DXy residues in honey samples with a limit of detection (LOD) of 0.1 pg.mL⁻¹ and an excellent selectivity when compared to the results of oxytetracycline (OXy) as analogous interfering compound. The proposed method is cheap, sensitive, selective, simple, and is applied successfully to detect DXy in honey with the recoveries of 87% and 95%. Considering these advantages, this system provides a further perspective for food quality control in industrial fields.

Keywords: doxycycline, electrochemical sensor, food control, gold nanoparticles, honey, molecular imprinted polymer

Procedia PDF Downloads 287

Authors: Mona Lisa M. Oliveira, Nara A. Policarpo, Ana Luiza B. P. Barros, Carla A. Silva

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Selective catalytic reduction systems for nitrogen oxides reduction by ammonia has been the chosen technology by most of diesel vehicle (i.e. bus and truck) manufacturers in Brazil, as also in Europe. Furthermore, at some conditions, over-stoichiometric ammonia availability is also needed that increases the NH₃ slips even more. Ammonia (NH₃) by this vehicle exhaust aftertreatment system provides a maximum efficiency of NOx removal if a significant amount of NH₃ is stored on its catalyst surface. In the other words, the practice shows that slightly less than 100% of the NOx conversion is usually targeted, so that the aqueous urea solution hydrolyzes to NH₃ via other species formation, under relatively low temperatures. This paper presents a model based on neural networks integrated with a road vehicle simulator that allows to estimate NH₃-slip emission factors for different driving conditions and patterns. The proposed model generates high NH₃slips which are not also limited in Brazil, but more efforts needed to be made to elucidate the contribution of vehicle-emitted NH₃ to the urban atmosphere.

Keywords: ammonia slip, neural-network, vehicles emissions, SCR-NOx

Procedia PDF Downloads 182

Authors: Tanusree Moitra, Garga Chatterjee, Diganta Mukherjee, Anjali Ghosh

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Stroop task is considered to be an important measure of selective attention. However, the color – word Stroop task cannot be administered to the illiterate population. Some of the participants in the present study are illiterate, therefore, object – color Stroop task was used among male juvenile delinquents of India and Bangladesh citizenship (IC & BC), housed in delinquent home in India. The purpose of the study is to test the hypothesis that over - selective attention is present among juvenile delinquents across both the countries. Eighty juvenile delinquents and matched control of 12 – 18 years (50 IC juvenile delinquents, 30 BC juvenile delinquents and 50 Indian control) were shown 24 familiar objects in both typical (e.g. a red apple) and atypical (e.g. a blue apple) color. Repeated – measure factorial ANOVA was used and it was found that all the three groups have taken longer response time in the atypical condition compared to the typical condition. However, contrary to the over - selective attention hypothesis, both groups of juvenile delinquents displayed higher Stroop interference in comparison to the matched control group. The findings of the study can be explained on the basis of anxiety score. IC and BC juvenile delinquents have high anxiety score compared to the control group which indicates that increased anxiety is correlated with the interference produced by the atypical color object stimuli when compared with the typical object stimuli. Funding acknowledgement: Authors acknowledge Department of Science and Technology, Government of India for financial support to the first author of the paper vide Reference no. SR/CSRI/PDF -01/2013 under Cognitive Science Research Initiative (CSRI) to carry out this work.

Keywords: Bangladesh, India, male juvenile delinquent, objects - color Stroop task

Procedia PDF Downloads 315

Authors: Xi Quan Cheng, Yan Chao Xu, Xu Jiang, Lu Shao, Cher Hon Lau

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A hydrophilic thin-film-composite (TFC) nanofiltration (NF) membrane has been developed through the interfacial polymerization (IP) of amino-functional polyethylene glycol (PEG) and trimesoyl chloride. The selective layer is formed on a polyethersulfone (PES) support that is characterized using FTIR, XPS and SEM, and is dependent on monomer immersion duration, and the concentration of monomers and additives. The higher hydrophilicity alongside the larger pore size of the PEG-based selective layer is the key to a high water flux of 66.0 L m-2 h-1 at 5.0 bar. With mean pore radius of 0.42 nm and narrow pore size distribution, the MgSO4 rejections of the PEG based PA TFC NF membranes can reach up to 80.2 %. The hydrophilic PEG based membranes shows positive charged since the isoelectric points range from pH=8.9 to pH=9.1 and the rejection rates for different salts of the novel membranes are in the order of R(MgCl2)>R(MgSO4)>R(NaCl)>R(Na2SO4). The pore sizes and water permeability of these membranes are tailored by varying the molecular weight and molecular architecture of amino-functional PEG. Due to the unique structure of the selective layer of the PEG based membranes consisting of saturated aliphatic construction unit (CH2-CH2-O), the membranes demonstrate dual resistance to fouling and chlorine. The membranes maintain good salt rejections and high water flux of PEG based membranes after treatment by 2000 ppm NaClO for 24 hours. Interestingly, the PEG based membranes exhibit excellent fouling resistance with a water flux recovery of 90.2 % using BSA as a model molecule. More importantly, the hydrophilic PEG based NF membranes have been exploited to separate several water soluble antibiotics (such as tobramycin, an aminoglycoside antibiotic applied in the treatment of various types of bacterial infections), showing excellent performance in concentration or removal of antibioics.

Keywords: nanofiltration, antibiotic separation, hydrophilic membrane, high flux

Procedia PDF Downloads 292

Authors: Adebisi Adunola Demehin, Wanlaya Thamnarak, Jaruwan Chatwichien, Chatchakorn Eurtivong, Kiattawee Choowongkomon, Somsak Ruchirawat, Nopporn Thasana

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The epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein involved in cellular signalling processes and, its aberrant activity is crucial in the development of many cancers such as lung cancer. Selaginellaceae are fern allies that have long been used in Chinese traditional medicine to treat various cancer types, especially lung cancer. Biflavonoids, the major secondary metabolites in Selaginellaceae, have numerous pharmacological activities, including anti-cancer and anti-inflammatory. For instance, amentoflavone induces a cytotoxic effect in the human NSCLC cell line via the inhibition of PARP-1. However, to the best of our knowledge, there are no studies on biflavonoids as EGFR inhibitors. Thus, this study aims to investigate the EGFR inhibitory activities of biflavonoids isolated from Selaginella siamensis and Selaginella bryopteris. Amentoflavone, tetrahydroamentoflavone, sciadopitysin, robustaflavone, robustaflavone-4-methylether, delicaflavone, and chrysocauloflavone were isolated from the ethyl-acetate extract of the whole plants. The structures were determined using NMR spectroscopy and mass spectrometry. In vitro study was conducted to evaluate their cytotoxicity against A549, HEPG2, and T47D human cancer cell lines using the MTT assay. In addition, a target-based assay was performed to investigate their EGFR inhibitory activity using the kinase inhibition assay. Finally, a molecular docking study was conducted to predict the binding modes of the compounds. Robustaflavone-4-methylether and delicaflavone showed the best cytotoxic activity on all the cell lines with IC50 (µM) values of 18.9 ± 2.1 and 22.7 ± 3.3 on A549, respectively. Of these biflavonoids, delicaflavone showed the most potent EGFR inhibitory activity with an 84% relative inhibition at 0.02 nM using erlotinib as a positive control. Robustaflavone-4-methylether showed a 78% inhibition at 0.15 nM. The docking scores obtained from the molecular docking study correlated with the kinase inhibition assay. Robustaflavone-4-methylether and delicaflavone had a docking score of 72.0 and 86.5, respectively. The inhibitory activity of delicaflavone seemed to be linked with the C2”=C3” and 3-O-4”’ linkage pattern. Thus, this study suggests that the structural features of these compounds could serve as a basis for developing new EGFR-TK inhibitors.

Keywords: anticancer, biflavonoids, EGFR, molecular docking, Selaginellaceae

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Authors: Faisal A. Salih, V. V. Egorov

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Verapamil is a drug used in medicine for arrhythmia, angina, and hypertension as a calcium channel blocker. In this study, a Verapamil-selective electrode was prepared, and the concentrations of the components in the membrane were as follows: PVC (32.8 wt %), O-NPhOE (66.6 wt %), and KTPClPB (0.6 wt % or approximately 0.01 M). The inner solution containing verapamil hydrochloride 1 x 10⁻³ M was introduced, and the electrodes were conditioned overnight in 1 x 10⁻³ M verapamil hydrochloride solution in 1 x 10⁻³ M orthophosphoric acid. These studies have demonstrated that O-NPhOE and KTPClPB are the best plasticizers and ion exchangers, while both direct potentiometry and potentiometric titration methods can be used for the determination of verapamil hydrochloride in tablets and injection solutions. Normalized weights of verapamil per tablet (80.4±0.2, 80.7±0.2, 81.0±0.4 mg) were determined by direct potentiometry and potentiometric titration, respectively. Weights of verapamil per average tablet weight determined by the methods of direct potentiometry and potentiometric titration were" 80.4±0.2, 80.7±0.2 mg determined for the same set of tablets, respectively. The masses of verapamil in solutions for injection, determined by direct potentiometry for two ampoules from one set, were (5.00±0.015, 5.004±0.006) mg. In all cases, good reproducibility and excellent correspondence with the declared quantities were observed.

Keywords: verapamil, potentiometry, ion-selective electrode, lipophilic physiologically active amines

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Authors: Harish Rajak, Preeti Patel

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The application of histone deacetylase inhibitors is a well-known strategy in prevention of cancer which shows acceptable preclinical antitumor activity due to its ability of growth inhibition and apoptosis induction of cancer cell. Molecular docking were performed using Histone Deacetylase protein (PDB ID:1t69) and prepared series of hydroxamic acid based HDACIs. On the basis of docking study, it was predicted that compound 1 has significant binding interaction with HDAC protein and three hydrogen bond interactions takes place, which are essential for antitumor activity. On docking, most of the compounds exhibited better glide score values between -8 to -10 which is close to the glide score value of suberoylanilide hydroxamic acid. The pharmacophore hypotheses were developed using e-pharmacophore script and phase module. The 3D-QSAR models provided a good correlation between predicted and actual anticancer activity. Best QSAR model showed Q2 (0.7974), R2 (0.9200) and standard deviation (0.2308). QSAR visualization maps suggest that hydrogen bond acceptor groups at carbonyl group of cap region and hydrophobic groups at ortho, meta, para position of R9 were favorable for HDAC inhibitory activity. We established structure activity correlation using docking, pharmacophore modeling and atom based 3D QSAR model for hydroxamic acid based HDACIs.

Keywords: HDACIs, QSAR, e-pharmacophore, docking, suberoylanilide hydroxamic acid

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Authors: Sidra Shaw, Sarenna Shaw, Chae Joon Lee, Irimpan Mathews, Eric Koehn

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One of the biggest public health concerns of our time is increasing antimicrobial resistance. As of 2019, the CDC has documented more than 2.8 million serious antibiotic resistant infections in the United States. Currently, antibiotic resistant infections are directly implicated in over 750,000 deaths per year globally. On our current trajectory, British economist Jim O’Neill predicts that by 2050, an additional 10 million people (about half the population of New York) will die annually due to drug resistant infections. As a result, new biochemical pathways must be targeted to generate next generation antibiotic drugs that will be effective against drug resistant bacteria. One enticing target is the biosynthesis of DNA within bacteria, as few drugs interrupt this essential life process. Thymidylate synthase enzymes are essential for life as they catalyze the synthesis of a DNA building block, 2′-deoxythymidine-5′-monophosphate (dTMP). In humans, the thymidylate synthase enzyme (TSase) has been shown to be distinct from the flavin-dependent thymidylate synthase (FDTS) produced by many pathogenic bacteria. TSase and FDTS have distinct structures and mechanisms of catalysis, which should allow selective inhibition of FDTS over human TSase. Currently, C. diff is one of the most antibiotic resistant bacteria, and no drugs that target thymine biosynthesis exist for C. diff. Here we present the initial biochemical characterization of FDTS from C. diff. Specifically, we examine enzyme kinetics and binding features of this enzyme to determine the nature of interaction with ligands/inhibitors and understand the molecular mechanism of catalysis. This research will provide more insight into the targetability of the C. diff FDTS enzyme for novel antibiotic drugs.

Keywords: flavin-dependent thymidylate synthase, FDTS, clostridioides difficile, C. diff, antibiotic resistance, DNA synthesis, enzyme kinetics, binding features

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Authors: Yee-Ting Lee, Jyun-Rong Zhuang, Wen-Hsin Hsieh, An-Shik Yang

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Additive manufacturing (AM) is increasingly crucial in biomedical and aerospace industries. As a recently developed AM technique, selective laser melting (SLM) has become a commercial method for various manufacturing processes. However, the molten pool configuration during SLM of metal powders is a decisive issue for the product quality. It is very important to investigate the heat transfer characteristics during the laser heating process. In this work, the finite element method (FEM) software ANSYS^® (work bench module 16.0) was used to predict the unsteady temperature distribution for resolving molten pool dimensions with consideration of temperature-dependent thermal physical properties of TiAl6V4 at different laser powers and scanning speeds. The simulated results of the temperature distributions illustrated that the ratio of laser power to scanning speed can greatly influence the size of molten pool of titanium alloy powder for SLM development.

Keywords: additive manufacturing, finite element method, molten pool dimensions, selective laser melting

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Authors: Ncoza Dlova, Tivani Mashamba-Thompson

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Garcinia livingstonei (Clusiaceae) extracts, morelloflavone- 7″- sulphate and sargaol were shown to be effective against hyper-pigmentation through inhibition of tyrosinase enzyme, in vitro . The aim of this study is to elucidate the structural mechanism through which morelloflavone- 7″- sulphate and sargaol binds human tyrosinase. Implementing a homology model to construct a tyrosinase model using the crystal structure of a functional unit from Octopus hemocyanin (PDB: 1JS8) as a reference template enabled us to create a human tyrosinase model. Molecular dynamics and binding free energy calculations were optimized to enable molecular dynamics simulation of the copper dependent inhibitors. Results show the importance of the hydrogen bond formation morelloflavone- 7″- sulphate and sargaol between compound and active site residues. Both complexes demonstrated the metallic coordination between compound and arginine residue as well as copper ions within the active site. The comprehensive molecular insight gained from this study should be vital in understanding the binding mechanism morelloflavone- 7″- sulphate and sargaol. Moreover, these results will assist in the design of novel of metal ion dependent enzyme inhibitors as potential anti-hyper-pigmentation disorder therapies.

Keywords: hyper-pigmentation disorders, dyschromia African skin, morelloflavone- 7″- sulphate, sagoal

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Authors: Horia Păunescu

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Purpose: The study aimed to assess the depressant or antidepressant effects of several Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) in mice: the selective cyclooxygenase-2 (COX-2) inhibitor meloxicam, and the non-selective COX-1 and COX-2 inhibitors lornoxicam, sodium metamizole, and ketorolac. The current literature data regarding such effects of these agents are scarce. Materials and methods: The study was carried out on NMRI mice weighing 20-35 g, kept in a standard laboratory environment. The study was approved by the Ethics Committee of the University of Medicine and Pharmacy „Carol Davila”, Bucharest. The study agents were injected intraperitoneally, 10 mL/kg body weight (bw) 1 hour before the assessment of the locomotor activity by cage testing (n=10 mice/ group) and 2 hours before the forced swimming tests (n=15). The study agents were dissolved in normal saline (meloxicam, sodium metamizole), ethanol 11.8% v/v in normal saline (ketorolac), or water (lornoxicam), respectively. Negative and positive control agents were also given (amitryptilline in the forced swimming test). The cage floor used in the locomotor activity assessment was divided into 20 equal 10 cm squares. The forced swimming test involved partial immersion of the mice in cylinders (15/9cm height/diameter) filled with water (10 cm depth at 28C), where they were left for 6 minutes. The cage endpoint used in the locomotor activity assessment was the number of treaded squares. Four endpoints were used in the forced swimming test (immobility latency for the entire 6 minutes, and immobility, swimming, and climbing scores for the final 4 minutes of the swimming session), recorded by an observer that was "blinded" to the experimental design. The statistical analysis used the Levene test for variance homogeneity, ANOVA and post-hoc analysis as appropriate, Tukey or Tamhane tests.Results: No statistically significant increase or decrease in the number of treaded squares was seen in the locomotor activity assessment of any mice group. In the forced swimming test, amitryptilline showed an antidepressant effect in each experiment, at the 10 mg/kg bw dosage. Sodium metamizole was depressant at 100 mg/kg bw (increased the immobility score, p=0.049, Tamhane test), but not in lower dosages as well (25 and 50 mg/kg bw). Ketorolac showed an antidepressant effect at the intermediate dosage of 5 mg/kg bw, but not so in the dosages of 2.5 and 10 mg/kg bw, respectively (increased the swimming score, p=0.012, Tamhane test). Meloxicam and lornoxicam did not alter the forced swimming endpoints at any dosage level. Discussion: 1) Certain NSAIDs caused changes in the forced swimming patterns without interfering with locomotion. 2) Sodium metamizole showed a depressant effect, whereas ketorolac proved antidepressant. Conclusion: NSAID-induced mood changes are not class effects of these agents and apparently are independent of the type of inhibited cyclooxygenase (COX-1 or COX-2). Disclosure: This paper was co-financed from the European Social Fund, through the Sectorial Operational Programme Human Resources Development 2007-2013, project number POSDRU /159 /1.5 /S /138907 "Excellence in scientific interdisciplinary research, doctoral and postdoctoral, in the economic, social and medical fields -EXCELIS", coordinator The Bucharest University of Economic Studies.

Keywords: antidepressant, depressant, forced swim, NSAIDs

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Authors: Ye Jiang

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To examine how the relationships among multiple institutional logics vary over time and the factors that may impact this process, we conducted a 15-year in-depth longitudinal case study of a Higher Education Institution to examine its exploration in college student management. By employing constructive grounded theory, we developed a four-stage process model comprising separation, formalization, selective bridging, and embeddedness that showed how two contradictory logics become complementary, and finally become a new hybridized logic. We argue that selective bridging is an important step in changing inter-logic relations. We also found that ambidextrous leadership and situational sensemaking are two key factors that drive this process. Our contribution to the literature is threefold. First, we enhance the literature on the changing relationships among multiple institutional logics and our findings advance the understanding of relationships between multiple logics through a dynamic view. While most studies have tended to assume that the relationship among logics is static and persistently in a contentious state, we contend that the relationships among multiple institutional logics can change over time. Competitive logics can become complementary, and a new hybridized logic can emerge therefrom. The four-stage logic hybridization process model offers insights on the logic hybridization process, which is underexplored in the literature. Second, our research reveals that selective bridging is important in making conflicting logics compatible, and thus constitutes a key step in creating new hybridized logic dynamics. Our findings suggest that the relations between multiple logics are manageable and can thus be manipulated for organizational innovation. Finally, the factors influencing the variations in inter-logic relations enrich the understanding of the antecedents of these dynamics.

Keywords: institutional theory, institutional logics, ambidextrous leadership, situational sensemaking

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Authors: Malek Y. S. Ibrahim, Jeffrey A. Bennett, Milad Abolhasani

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Despite the potential of hydrogen (H2) storage in liquid organic carriers to achieve carbon neutrality, the energy required for H2 release and the cost of catalyst recycling has hindered its large-scale adoption. In response, a photo flow reactor packed with rhodium (Rh)/titania (TiO2) photocatalyst was reported for the continuous and selective acceptorless dehydrogenation of 1,2,3,4-tetrahydroquinoline to H2 gas and quinoline under visible light irradiation at room temperature. The tradeoff between the reactor pressure drop and its photocatalytic surface area was resolved by selective in-situ photodeposition of Rh in the photo flow reactor post-packing on the outer surface of the TiO2 microparticles available to photon flux, thereby reducing the optimal Rh loading by 10 times compared to a batch reactor, while facilitating catalyst reuse and regeneration. An example of using quinoline as a hydrogen acceptor to lower the energy of the hydrogen production step was demonstrated via the water-gas shift reaction.

Keywords: hydrogen storage, flow chemistry, photocatalysis, solar hydrogen

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Authors: Abd El-Aziz Said

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In this study, natural silica was used as an active, selective, reusable and eco-friendly catalyst for the liquid phase synthesis of iso-amyl, benzyl and cinnamyl esters. The original and calcined natural silica were characterized by TG-DTA, XRF, XRD, FTIR, SEM, and N2-sorption analysis. The surface acidity of the catalysts was determined using isopropanol dehydration and the strength of available acid sites was measured using chemisorption of pyridine (PY) and dimethyl pyridine (DMPY). The results of acidity specified that the acidic sites are of Brönsted type, while PY-TPD demonstrated that almost of the acidic sites over the surface of natural silica are of weak and intermediate strength. The catalytic activity of natural silica towards esterification of acetic acid with alcohols was extensively studied. The results revealed that natural silica had high catalytic activity with 100% selectivity to all targeted esters. In addition, the yields obtained in batch methods were 83, 81, and 80%, respectively, whereas these yields after simple distillation were improved 97, 99.5, and 90%, respectively.

Keywords: liquid-phase esterification, natural silica, acidity esters, characterization

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Authors: Shijie Liu, Jehnming Lin

Abstract:

This study mainly discussed the mechanical properties of selective laser sintered 304L stainless steel powder specimen. According to a single layer specimen sintering, the microstructure and porosity were observed to find out the proper sintering parameters. A multi-layer sintering experiment was conducted. Based on the microstructure and the integration between layers, the suitable parameters were found out. Finally, the sintered specimens were examined by metallographical inspection, hardness test, tensile test, and surface morphology measurement. The structure of the molten powder coated with unmelted powder was found in metallographic test. The hardness of the sintered stainless steel powder is greater than the raw material. The tensile strength is less than the raw material, and it is corresponding to different scanning paths. The specimen will have different patterns of cracking. It was found that the helical scanning path specimen will have a warpage deformation at the edge of the specimen. The S-scan path specimen surface is relatively flat.

Keywords: laser sintering, sintering path, microstructure, mechanical properties

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Authors: Bing–Jing Zhao, Chang-Kui Liu, Hong Wang, Min Hu

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Electron beam rapid manufacturing (EBRM) or Selective laser melting is an additive manufacturing process that uses 3D CAD data as a digital information source and energy in the form of a high-power laser beam or electron beam to create three-dimensional metal parts by fusing fine metallic powders together.Object:The present study was conducted to evaluate the mechanical properties ,the phase transformation,the corrosivity and the biocompatibility of Ti-6Al-4V by EBRM,SLM and forging technique.Method: Ti-6Al-4V alloy standard test pieces were manufactured by EBRM, SLM and forging technique according to AMS4999,GB/T228 and ISO 10993.The mechanical properties were analyzed by universal test machine. The phase transformation was analyzed by X-ray diffraction and scanning electron microscopy. The corrosivity was analyzed by electrochemical method. The biocompatibility was analyzed by co-culturing with mesenchymal stem cell and analyzed by scanning electron microscopy (SEM) and alkaline phosphatase assay (ALP) to evaluate cell adhesion and differentiation, respectively. Results: The mechanical properties, the phase transformation, the corrosivity and the biocompatibility of Ti-6Al-4V by EBRM、SLM were similar to forging and meet the mechanical property requirements of AMS4999 standard. a­phase microstructure for the EBM production contrast to the a’­phase microstructure of the SLM product. Mesenchymal stem cell adhesion and differentiation were well. Conclusion: The property of the Ti-6Al-4V alloy manufactured by EBRM and SLM technique can meet the medical standard from this study. But some further study should be proceeded in order to applying well in clinical practice.

Keywords: 3D printing, Electron Beam Rapid Manufacturing (EBRM), Selective Laser Melting (SLM), Computer Aided Design (CAD)

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Authors: Ahmad N. Abu-Baker

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This study investigated the corrosion of a group of heritage silver-copper alloy coins and their conservation treatment by potentiostatic methods. The corrosion products of the coins were characterized by a combination of scanning electron microscopy/ energy-dispersive X-ray spectroscopy (SEM/EDX) and X-ray diffraction (XRD) analyses. Cathodic polarization curves, measured by linear sweep voltammetry (LSV), also identified the corrosion products and the working conditions to treat the coins using a potentiostatic reduction method, which was monitored by chronoamperometry. The corrosion products showed that the decay mechanisms were dominated by selective attack on the copper-rich phases of the silver-copper alloys, which is consistent with an internal galvanic corrosion phenomenon, which leads to the deposition of copper corrosion products on the surface of the coins. Silver chloride was also detected on the coins, which reflects selective corrosion of the silver-rich phases under different chemical environments. The potentiostatic treatment showed excellent effectiveness in determining treatment parameters and monitoring the reduction process of the corrosion products on the coins, which helped to preserve surface details in the cleaning process and to prevent over-treatment.

Keywords: silver alloys, corrosion, conservation, heritage

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Authors: Faisal A. Salih

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Vinpocetine (Vin) is an ethyl ester of apovincamic acid and is a semisynthetic derivative of vincamine, an alkaloid from plants of the genus Periwinkle (plant) vinca minor. It was found that this compound stimulates cerebral metabolism: it increases the uptake of glucose and oxygen, as well as the consumption of these substances by the brain tissue. Vinpocetine enhances the flow of blood in the brain and has a vasodilating, antihypertensive, and antiplatelet effect. Vinpocetine seems to improve the human ability to acquire new memories and restore memories that have been lost. This drug has been clinically used for the treatment of cerebrovascular disorders such as stroke and dementia memory disorders, as well as in ophthalmology and otorhinolaryngology. It has no side effects, and no toxicity has been reported when using vinpocetine for a long time. For the quantitative determination of Vin in dosage forms, the HPLC methods are generally used. A promising alternative is potentiometry with Vin- selective electrode, which does not require expensive equipment and materials. Another advantage of the potentiometric method is that the pills and solutions for injections can be used directly without separation from matrix components, which reduces both analysis time and cost. In this study, it was found that the choice of a good plasticizer an electrode with the following membrane composition: PVC (32.8 wt.%), ortho-nitrophenyl octyl ether (66.6 wt.%), tetrakis-4-chlorophenyl borate (0.6 wt.%) exhibits excellent analytical performance: lower detection limit (LDL) 1.2•10⁻⁷ M, linear response range (LRR) 1∙10⁻³–3.9∙10⁻⁶ M, the slope of the electrode function 56.2±0.2 mV/decade). Vin masses per average tablet weight determined by direct potentiometry (DP) and potentiometric titration (PT) methods for the two different sets of 10 tablets were (100.35±0.2–100.36±0.1) mg for two sets of blister packs. The mass fraction of Vin in individual tablets, determined using DP, was (9.87 ± 0.02–10.16 ±0.02) mg, while the RSD was (0.13–0.35%). The procedure has very good reproducibility, and excellent compliance with the declared amounts was observed.

Keywords: vinpocetine, potentiometry, ion selective electrode, pharmaceutical analysis

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Authors: B. Makhlouf, O. Bouchhida, M. Nibouche, K. Laidi

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A variety of methods for selective harmonics elimination pulse width modulation have been developed, the most frequently used for real-time implementation based on look-up tables method. To address real-time requirements based in modified carrier signal is proposed in the presented work, with a general formulation to real-time harmonics control/elimination in switched inverters. Firstly, the proposed method has been demonstrated for a single value of the modulation index. However, in reality, this parameter is variable as a consequence of the voltage (amplitude) variability. In this context, a simple interpolation method for calculating the modified sine carrier signal is proposed. The method allows a continuous adjustment in both amplitude and frequency of the fundamental. To assess the performance of the proposed method, software simulations and hardware experiments have been carried out in the case of a single-phase inverter. Obtained results are very satisfactory.

Keywords: harmonic elimination, Particle Swarm Optimisation (PSO), polynomial interpolation, pulse width modulation, real-time harmonics control, voltage inverter

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Authors: Mike Wei, Nebu Koshy, Koen van Besien, Giorgio Inghirami, Steven M. Horwitz

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T-cell prolymphocytic leukemia (T-PLL) is a rare hematologic disease characterized by a T-cell phenotype, rapid progression, and poor prognosis with median survival of less than a year. Alemtuzumab-based chemotherapy has increased the rate of complete remissions but these are often short-lived, and allogeneic transplant is considered the only curative therapy. In recent studies, JAK3 activating mutations have been identified in T-cell cancers, with T-PLL having the highest rate of JAK3 mutations (30 – 42%). As such, T-PLL is a model disease for evaluating the utility of JAK3 inhibitors. We present a case of a 64-year-old man with relapsed-refractory T-PLL. He was initially treated with alemtuzumab and obtained complete response and was consolidated with matched unrelated donor stem cell transplant. His disease stayed in remission for approximately 1.5 years before relapse, which was then treated with a clinical trial of romidepsin-lenalidomide (partial responses then progression at 6 months) and later alemtuzumab. Due to complications of myelosuppression and CMV reactivation, his treatment was interrupted leading to disease progression. The doubling time of lymphocyte count was approximately 20 days and over a span of 60 days the lymphocyte count rose from 8 x 109/L to 68 x 109/L. Exon sequencing showed a JAK3 mutation. The patient consented to and was treated with FDA-approved tofacitinib (initially 5 mg BID, increased to 10 mg BID after 15 days of treatment). An initial decrease in lymphocyte count was followed by progression. In vitro treatment of the patient’s cells showed modest effects of tofacitinib and ruxolitinib as single agents, in the range of doxorubicin, but synergy between the agents. After 40 days of treatment with tofacitinib and with a lymphocyte count of 150 x 109/L, ruxolitinib (5mg BID) was added. Over the 60 days since dual inhibition was started, the lymphocyte count has stabilized. The patient has remained completely asymptomatic during treatment with tofacitinib and ruxolitinib. Neutrophil count has remained normal. Platelet count and hemoglobin have however declined from ~50 x109/L to ~30 x109/L and from 11 g/dL to 8.1 g/dL respectively, since the introduction of ruxolitinib. The stabilization in lymphocyte count confirms the clinical activity of JAK inhibitors in T-PLL as suggested by the presence of JAK3 mutations and by in-vitro assays. It also suggests clinical synergy between ruxolitinib and tofacitinib in this setting. Prospective studies of JAK inhibitors in PLL patients with formal dose-finding studies are needed.

Keywords: tofacitinib, ruxolitinib, T-cell prolymphocytic leukemia, JAK3

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Authors: John Hang Leung, Shyh-Yau Wang, Hei-Tung Yip, Fion, Ho Tsung-chin, Agnes LF Chan

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Objectives: Platinum-resistant ovarian cancer has a short overall survival of 9–12 months and limited treatment options. The combination of immunotherapy and targeted therapy appears to be a promising treatment option for patients with ovarian cancer, particularly to patients with platinum-resistant recurrent ovarian cancer (PRrOC). However, there are no direct head-to-head clinical trials comparing their efficacy and toxicity. We, therefore, used a network to directly and indirectly compare seven newer immunotherapies or targeted therapies combined with chemotherapy in platinum-resistant relapsed ovarian cancer, including antibody-drug conjugates, PD-1 (Programmed death-1) and PD-L1 (Programmed death-ligand 1), PARP (Poly ADP-ribose polymerase) inhibitors, TKIs (Tyrosine kinase inhibitors), and antiangiogenic agents. Methods: We searched PubMed (Public/Publisher MEDLINE), EMBASE (Excerpta Medica Database), and the Cochrane Library electronic databases for phase II and III trials involving PRrOC patients treated with immunotherapy or targeted therapy plus chemotherapy. The quality of included trials was assessed using the GRADE method. The primary outcomes compared were progression-free survival, the secondary outcomes were overall survival and safety. Results: Seven randomized controlled trials involving a total of 2058 PRrOC patients were included in this analysis. Bevacizumab plus chemotherapy showed statistically significant differences in PFS (Progression-free survival) but not OS (Overall survival) for all interested targets and immunotherapy regimens; however, according to the heatmap analysis, bevacizumab plus chemotherapy had a statistically significant risk of ≥grade 3 SAEs (Severe adverse effects), particularly hematological severe adverse events (neutropenia, anemia, leukopenia, and thrombocytopenia). Conclusions: Bevacizumab plus chemotherapy resulted in better PFS as compared with all interested regimens for the treatment of PRrOC. However, statistical differences in SAEs as bevacizumab plus chemotherapy is associated with a greater risk for hematological SAE.

Keywords: platinum-resistant recurrent ovarian cancer, network meta-analysis, immune checkpoint inhibitors, target therapy, antiangiogenic agents

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Authors: L. Kloetzer, M. Poştaru, A. I. Galaction, D. Caşcaval

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Gentamicin is an aminoglycoside antibiotic industrially obtained by biosynthesis of Micromonospora purpurea or echinospora, the product being a complex mixture of components with very similar structures. Among them, three exhibit the most important biological activity: gentamicins C1, C1a, C2, and C2a. The separation of gentamicin from the fermentation broths at industrial scale is rather difficult and it does not allow the fractionation of the complex mixture of gentamicins in order to increase the therapeutic activity of the product. The aim of our experiments is to analyze the possibility to selectively separate the less active gentamicin, namely gentamicin C1, from the biosynthetic mixture by reactive extraction with di-(2-ethylhexyl) phosphoric acid (D2EHPA) dissolved in dichloromethane, followed selective re-extraction of the most active gentamicins C1a, C2, and C2a. The experiments on the reactive extraction of gentamicins indicated the possibility to separate selectively the gentamicin C1 from the mixture obtained by biosynthesis. The extraction selectivity is positively influenced by increasing the pH-value of an aqueous solution and by using a D2EHPA concentration in organic phase closer to the value needed for an equimolecular ratio between the extractant and this gentamicin. For quantifying the selectivity of separation, the selectivity factor, calculated as the ratio between the degree of reactive extraction of gentamicin C1 and the overall extraction degree of gentamicins were used. The possibility to remove the gentamicin C1 at an extractant concentration of 10 g l-1 and pH = 8 is presented. In these conditions, it was obtained the maximum value of the selectivity factor of 2.14, which corresponds to the modification of the gentamicin C1 concentration from 31.92% in the biosynthetic mixture to 72% in the extract. The re-extraction of gentamicins C1, C1a, C2, and C2a with sulfuric acid from the extract previously obtained by reactive extraction (mixture A – extract obtained by non-selective reactive extraction; mixture B – extract obtained by selective reactive extraction) allows for separating selectively the most active gentamicins C1a, C2, and C2a. For recovering only the active gentamicins C1a, C2, and C2a, the re-extraction must be carried out at very low acid concentrations, far below those corresponding to the stoichiometry of its chemical reactions with these gentamicins. Therefore, the mixture resulted by re-extraction contained 92.6% gentamicins C1a, C2, and C2a. By bringing together the aqueous solutions obtained by reactive extraction and re-extraction, the overall content of the active gentamicins in the final product becomes 89%, their loss reaching 0.3% related to the initial biosynthetic product.

Keywords: di-(2-ethylhexyl) phosphoric acid, gentamicin, reactive extraction, selectivity factor

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Authors: Felicia Segeth, Florian G. Klein, Lea Berger, Andreas Kolk, Per S. Holm

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The entry of oncolytic viruses (OVs) into clinical application opens groundbreaking changes in current and future treatment regimens. However, despite their potent anti-cancer activity in vitro, clinical studies revealed limitations of OVs as monotherapy. The same applies to CDK 4/6 inhibitors (CDK4/6i) targeting cell cycle as well as bromodomain and extra-terminal domain inhibitors (BETi) targeting gene expression. In this study, the anti-tumoral effect of XVir-N-31, an YB-1 dependent oncolytic adenovirus, was evaluated in combination with Ribociclib, a CDK4/6i, and JQ1, a BETi. The head and neck squamous cell carcinoma (HNSCC) cell lines Fadu, SAS, and Cal-33 were used. DNA replication and gene expression of XVir-N-31 was measured by RT-qPCR, protein expression by western blotting, and cell lysis by SRB assays. Treatment with CDK4/6i and BETi increased viral gene expression, viral DNA replication, and viral particle formation. The data show that the combination of oncolytic adenovirus XVir-N-31 with CDK4/6i & BETi acts highly synergistic in cancer cell lysis. Furthermore, additional molecular analyses on this subject demonstrate that the positive transcription elongation factor P-TEFb plays a decisive role in this regard, indicating an influence of the combinational therapy on gene transcription control. The combination of CDK4/6i & BETi and XVir-N-31 is an attractive strategy to achieve substantial cancer cell killing and is highly suitable for clinical testing.

Keywords: adenovirus, BET, CDK4/6, HNSCC, P-TEFb, YB-1

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