Search results for: reactive MgO cement

Authors: Pauline Nyssen, Ange Mouithys-Mickalad, Maryse Hoebeke

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Inflammation is a complex physiological phenomenon involving chemical and enzymatic mechanisms. Polymorphonuclear neutrophil leukocytes (PMNs) play an important role by producing reactive oxygen species (ROS) and releasing myeloperoxidase (MPO), a pro-oxidant enzyme. Released both in the phagolysosome and the extracellular medium, MPO produces during its peroxidase and halogenation cycles oxidant species, including hypochlorous acid, involved in the destruction of pathogen agents, like bacteria or viruses. Inflammatory pathologies, like rheumatoid arthritis, atherosclerosis induce an excessive stimulation of the PMNs and, therefore, an uncontrolled release of ROS and MPO in the extracellular medium, causing severe damages to the surrounding tissues and biomolecules such as proteins, lipids, and DNA. The treatment of chronic inflammatory pathologies remains a challenge. For many years, MPO has been used as a target for the development of effective treatments. Numerous studies have been focused on the design of new drugs presenting more efficient MPO inhibitory properties. However, some designed inhibitors can be toxic. An alternative consists of assessing the potential inhibitory action of clinically-known molecules, having antioxidant activity. Propofol, 2,6-diisopropyl phenol, which is used as an intravenous anesthetic agent, meets these requirements. Besides its anesthetic action employed to induce a sedative state during surgery or in intensive care units, propofol and its injectable form Diprivan indeed present antioxidant properties and act as ROS and free radical scavengers. A study has also evidenced the ability of propofol to inhibit the formation of the neutrophil extracellular traps fibers, which are important to trap pathogen microorganisms during the inflammation process. The aim of this study was to investigate the potential inhibitory action mechanism of propofol and Diprivan on MPO activity. To go into the anti-inflammatory action of propofol in-depth, two of its oxidative derivatives, 2,6-diisopropyl-1,4-p-benzoquinone (PPFQ) and 3,5,3’,5’-tetra isopropyl-(4,4’)-diphenoquinone (PPFDQ), were studied regarding their inhibitory action. Specific immunological extraction followed by enzyme detection (SIEFED) and molecular modeling have evidenced the low anti-catalytic action of propofol. Stopped-flow absorption spectroscopy and direct MPO activity analysis have proved that propofol acts as a reversible MPO inhibitor by interacting as a reductive substrate in the peroxidase cycle and promoting the accumulation of redox compound II. Overall, Diprivan exhibited a weaker inhibitory action than the active molecule propofol. In contrast, PPFQ seemed to bind and obstruct the enzyme active site, preventing the trigger of the MPO oxidant cycles. PPFQ induced a better chlorination cycle inhibition at basic and neutral pH in comparison to propofol. PPFDQ did not show any MPO inhibition activity. The three interest molecules have also demonstrated their inhibition ability on an important step of the inflammation pathway, the PMNs superoxide anions production, thanks to EPR spectroscopy and chemiluminescence. In conclusion, propofol presents an interesting immunomodulatory activity by acting as a reductive substrate in the peroxidase cycle of MPO, slowing down its activity, whereas PPFQ acts more as an anti-catalytic substrate. Although PPFDQ has no impact on MPO, it can act on the inflammation process by inhibiting the superoxide anions production by PMNs.

Keywords: Diprivan, inhibitor, myeloperoxidase, propofol, spectroscopy

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Authors: Sunil Arora, Anitya Kumar Jena, S. A. Ravi

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India is at the cusp of major reforms in the hydrocarbon sector. Oil and gas sector is highly liberalised to attract private investment and to increase domestic production. Major hydrocarbon Exploration & Production (E&P) activity here have been undertaken by Government owned companies but with easing up and reworking of hydro carbon exploration licensing policies private players have also joined the fray towards achieving energy security for India. Government of India has come up with policy and administrative reforms including Hydrocarbon Exploration and Licensing Policy (HELP), Sagarmala (port-led development with coastal connectivity), and Development of Small Discovered Fields, etc. with the intention to make industry friendly conditions for investment, ease of doing business and reduce gestation period. To harness the potential resources of Deep water and Ultra deep water, High Pressure – High Temperature (HP-HT) regions, Coal Bed Methane (CBM), Shale Hydrocarbons besides Gas Hydrates, participation shall be required from both domestic and international players. Companies engaged in E&P activities in India have traditionally been managing through their captive supply base, but with crude prices under hammer, the need is being felt to outsource non-core activities. This necessitates establishment of a robust support services to cater to E&P Industry, which is currently non-existent to meet the bourgeon challenges. This paper outlines an agenda for creating an Integrated Services Hub (ISH) under Special Economic Zone (SEZ) to facilitate complete gamut of non-core support activities of E&P industry. This responsive and proficient multi-usage facility becomes viable with better resource utilization, economies of scale to offer cost effective services. The concept envisages companies to bring-in their core technical expertise leaving complete hardware peripherals outsourced to this ISH. The Integrated Services Hub, complying with the best in class global standards, shall typically provide following Services under Single Window Solution, but not limited to: a) Logistics including supply base operations, transport of manpower and material, helicopters, offshore supply vessels, warehousing, inventory management, sourcing and procurement activities, international freight forwarding, domestic trucking, customs clearance service etc. b) Trained/Experienced pool of competent Manpower (Technical, Security etc.) will be available for engagement by companies on either short or long term basis depending upon the requirements with provisions of meeting any training requirements. c) Specialized Services through tie-up with global best companies for Crisis Management, Mud/Cement, Fishing, Floating Dry-dock besides provision of Workshop, Repair and Testing facilities, etc. d) Tools and Tackles including drill strings, etc. A pre-established Integrated Services Hub shall facilitate an early start-up of activities with substantial savings in time lines. This model can be replicated at other parts of the world to expedite E&P activities.

Keywords: integrated service hub, India, oil gas, offshore supply base

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Authors: R. Verwiebe, L. Seewann, M. Wolf

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This presentation addresses marginalization and discrimination as experienced by young academics with a migrant background in the Austrian labor market. Focusing on second generation academics of Central Eastern European and Turkish descent we explore two major issues. First, we ask whether their career-entry and everyday professional life entails origin-specific barriers. As educational residents, they show competences which, when lacking, tend to be drawn upon to explain discrimination: excellent linguistic skills, accredited high-level training, and networks. Second, we concentrate on how this group reacts to discrimination and overcomes experiences of marginalization. To answer these questions, we utilize recent sociological and social psychological theories that focus on the diversity of individual experiences. This distinguishes us from a long tradition of research that has dealt with the motives that inform discrimination, but has less often considered the effects on those concerned. Similarly, applied coping strategies have less often been investigated, though they may provide unique insights into current problematic issues. Building upon present literature, we follow recent discrimination research incorporating the concepts of ‘multiple discrimination’, ‘subtle discrimination’, and ‘visual social markers’. 21 problem-centered interviews are the empirical foundation underlying this study. The interviewees completed their entire educational career in Austria, graduated in different universities and disciplines and are working in their first post-graduate jobs (career entry phase). In our analysis, we combined thematic charting with a coding method. The results emanating from our empirical material indicated a variety of discrimination experiences ranging from barely perceptible disadvantages to directly articulated and overt marginalization. The spectrum of experiences covered stereotypical suppositions at job interviews, the disavowal of competencies, symbolic or social exclusion by new colleges, restricted professional participation (e.g. customer contact) and non-recruitment due to religious or ethnical markers (e.g. headscarves). In these experiences the role of the academics education level, networks, or competences seemed to be minimal, as negative prejudice on the basis of visible ‘social markers’ operated ‘ex-ante’. The coping strategies identified in overcoming such barriers are: an increased emphasis on effort, avoidance of potentially marginalizing situations, direct resistance (mostly in the form of verbal opposition) and dismissal of negative experiences by ignoring or ironizing the situation. In some cases, the academics drew into their specific competences, such as an intellectual approach of studying specialist literature, focus on their intercultural competences or planning to migrate back to their parent’s country of origin. Our analysis further suggests a distinction between reactive (i.e. to act on and respond to experienced discrimination) and preventative strategies (applied to obviate discrimination) of coping. In light of our results, we would like to stress that the tension between educational and professional success experienced by academics with a migrant background – and the barriers and marginalization they continue to face – are essential issues to be introduced to socio-political discourse. It seems imperative to publicly accentuate the growing social, political and economic significance of this group, their educational aspirations, as well as their experiences of achievement and difficulties.

Keywords: coping strategies, discrimination, labor market, second generation university graduates

Procedia PDF Downloads 192

Authors: Ching-Sung Lee, Wei-Chou Hsu, Han-Yin Liu, Hung-Hsi Huang, Si-Fu Chen, Yun-Jung Yang, Bo-Chun Chiang, Yu-Chuang Chen, Shen-Tin Yang

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AlGaN/GaN high electron mobility transistors (HEMTs) have been intensively studied due to their intrinsic advantages of high breakdown electric field, high electron saturation velocity, and excellent chemical stability. They are also suitable for ultra-violet (UV) photodetection due to the corresponding wavelengths of GaN bandgap. To improve the optical responsivity by decreasing the dark current due to gate leakage problems and limited Schottky barrier heights in GaN-based HEMT devices, various metal-oxide-semiconductor HEMTs (MOS-HEMTs) have been devised by using atomic layer deposition (ALD), molecular beam epitaxy (MBE), metal-organic chemical vapor deposition (MOCVD), liquid phase deposition (LPD), and RF sputtering. The gate dielectrics include MgO, HfO2, Al2O3, La2O3, and TiO2. In order to provide complementary circuit operation, enhancement-mode (E-mode) devices have been lately studied using techniques of fluorine treatment, p-type capper, piezoneutralization layer, and MOS-gate structure. This work reports an Al2O3-dielectric Al0.25Ga0.75N/GaN E-mode MOS-HEMT design by using a cost-effective ozone water oxidization technique. The present ozone oxidization method advantages of low cost processing facility, processing simplicity, compatibility to device fabrication, and room-temperature operation under atmospheric pressure. It can further reduce the gate-to-channel distance and improve the transocnductance (gm) gain for a specific oxide thickness, since the formation of the Al2O3 will consume part of the AlGaN barrier at the same time. The epitaxial structure of the studied devices was grown by using the MOCVD technique. On a Si substrate, the layer structures include a 3.9 m C-doped GaN buffer, a 300 nm GaN channel layer, and a 5 nm Al0.25Ga0.75N barrier layer. Mesa etching was performed to provide electrical isolation by using an inductively coupled-plasma reactive ion etcher (ICP-RIE). Ti/Al/Au were thermally evaporated and annealed to form the source and drain ohmic contacts. The device was immersed into the H2O2 solution pumped with ozone gas generated by using an OW-K2 ozone generator. Ni/Au were deposited as the gate electrode to complete device fabrication of MOS-HEMT. The formed Al2O3 oxide thickness 7 nm and the remained AlGaN barrier thickness is 2 nm. A reference HEMT device has also been fabricated in comparison on the same epitaxial structure. The gate dimensions are 1.2 × 100 µm 2 with a source-to-drain spacing of 5 μm for both devices. The dielectric constant (k) of Al2O3 was characterized to be 9.2 by using C-V measurement. Reduced interface state density after oxidization has been verified by the low-frequency noise spectra, Hooge coefficients, and pulse I-V measurement. Improved device characteristics at temperatures of 300 K-450 K have been achieved for the present MOS-HEMT design. Consequently, Al2O3-dielectric Al0.25Ga0.75N/GaN E-mode MOS-HEMTs by using the ozone water oxidization method are reported. In comparison with a conventional Schottky-gate HEMT, the MOS-HEMT design has demonstrated excellent enhancements of 138% (176%) in gm, max, 118% (139%) in IDS, max, 53% (62%) in BVGD, 3 (2)-order reduction in IG leakage at VGD = -60 V at 300 (450) K. This work is promising for millimeter-wave integrated circuit (MMIC) and three-terminal active UV photodetector applications.

Keywords: MOS-HEMT, enhancement mode, AlGaN/GaN, passivation, ozone water oxidation, gate leakage

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Authors: Elsie M. Nolte, Annie M. Joubert, Roy Lakier, Maryke Etsebeth, Jolene M. Helena, Marcel Verwey, Laurence Lafanechere, Anne E. Theron

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Treatment regimens for breast- and lung cancers may include both radiation- and chemotherapy. Ideally, a pharmaceutical agent which selectively sensitizes cancer cells to gamma (γ)-radiation would allow administration of lower doses of each modality, yielding synergistic anti-cancer benefits and lower metastasis occurrence, in addition to decreasing the side-effect profiles. A range of 2-methoxyestradiol (2-ME) analogues, namely 2-ethyl-3-O-sulphamoyl-estra-1,3,5 (10) 15-tetraene-3-ol-17one (ESE-15-one), 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10),15-tetraen-17-ol (ESE-15-ol) and 2-ethyl-3-O-sulphamoyl-estra-1,3,5(10)16-tetraene (ESE-16) were in silico-designed by our laboratory, with the aim of improving the parent compound’s bioavailability in vivo. The main effect of these compounds is the disruption of microtubule dynamics with a resultant mitotic accumulation and induction of programmed cell death in various cancer cell lines. This in vitro study aimed to determine the cellular responses involved in the radiation sensitization effects of these analogues at low doses in breast- and lung cancer cell lines. The oestrogen receptor positive MCF-7-, oestrogen receptor negative MDA-MB-231- and triple negative BT-20 breast cancer cell lines as well as the A549 lung cancer cell line were used. The minimal compound- and radiation doses able to induce apoptosis were determined using annexin-V and cell cycle progression markers. These doses (cell line dependent) were used to pre-sensitize the cancer cells 24 hours prior to 6 gray (Gy) radiation. Experiments were conducted on samples exposed to the individual- as well as the combination treatment conditions in order to determine whether the combination treatment yielded an additive cell death response. Morphological studies included light-, fluorescence- and transmission electron microscopy. Apoptosis induction was determined by flow cytometry employing annexin V, cell cycle analysis, B-cell lymphoma 2 (Bcl-2) signalling, as well as reactive oxygen species (ROS) production. Clonogenic studies were performed by allowing colony formation for 10 days post radiation. Deoxyribonucleic acid (DNA) damage was quantified via γ-H2AX foci and micronuclei quantification. Amplification of the p53 signalling pathway was determined by western blot. Results indicated that exposing breast- and lung cancer cells to nanomolar concentrations of these analogues 24 hours prior to γ-radiation induced more cell death than the compound- and radiation treatments alone. Hypercondensed chromatin, decreased cell density, a damaged cytoskeleton and an increase in apoptotic body formation were observed in cells exposed to the combination treatment condition. An increased number of cells present in the sub-G1 phase as well as increased annexin-V staining, elevation of ROS formation and decreased Bcl-2 signalling confirmed the additive effect of the combination treatment. In addition, colony formation decreased significantly. p53 signalling pathways were significantly amplified in cells exposed to the analogues 24 hours prior to radiation, as was the amount of DNA damage. In conclusion, our results indicated that pre-treatment of breast- and lung cancer cells with low doses of 2-ME analogues sensitized breast- and lung cancer cells to γ-radiation and induced apoptosis more so than the individual treatments alone. Future studies will focus on the effect of the combination treatment on non-malignant cellular counterparts.

Keywords: cancer, microtubule dynamics, radiation therapy, radiosensitization

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Authors: Sofia N. Gonçalves, Duarte M. S. Albuquerque, José C. F. Pereira

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Microwave technology has been gaining importance in contributing to decarbonization processes in high energy demand industries. Despite the several numerical models presented in the literature, a proper Verification and Validation exercise is still lacking. This is important and required to evaluate the physical process model accuracy and adequacy. Another issue addresses impedance matching, which is an important mechanism used in microwave experiments to increase electromagnetic efficiency. Such mechanism is not available in current computational tools, thus requiring an external numerical procedure. A numerical model was implemented to study the continuous processing of limestone with microwave heating. This process requires the material to be heated until a certain temperature that will prompt a highly endothermic reaction. Both a 2D and 3D model were built in COMSOL Multiphysics to solve the two-way coupling between Maxwell and Energy equations, along with the coupling between both heat transfer phenomena and limestone endothermic reaction. The 2D model was used to study and evaluate the required numerical procedure, being also a benchmark test, allowing other authors to implement impedance matching procedures. To achieve this goal, a controller built in MATLAB was used to continuously matching the cavity impedance and predicting the required energy for the system, thus successfully avoiding energy inefficiencies. The 3D model reproduces realistic results and therefore supports the main conclusions of this work. Limestone was modeled as a continuous flow under the transport of concentrated species, whose material and kinetics properties were taken from literature. Verification and Validation of the coupled model was taken separately from the chemical kinetic model. The chemical kinetic model was found to correctly describe the chosen kinetic equation by comparing numerical results with experimental data. A solution verification was made for the electromagnetic interface, where second order and fourth order accurate schemes were found for linear and quadratic elements, respectively, with numerical uncertainty lower than 0.03%. Regarding the coupled model, it was demonstrated that the numerical error would diverge for the heat transfer interface with the mapped mesh. Results showed numerical stability for the triangular mesh, and the numerical uncertainty was less than 0.1%. This study evaluated limestone velocity, heat transfer, and load influence on thermal decomposition and overall process efficiency. The velocity and heat transfer coefficient were studied with the 2D model, while different loads of material were studied with the 3D model. Both models demonstrated to be highly unstable when solving non-linear temperature distributions. High velocity flows exhibited propensity to thermal runways, and the thermal efficiency showed the tendency to stabilize for the higher velocities and higher filling ratio. Microwave efficiency denoted an optimal velocity for each heat transfer coefficient, pointing out that electromagnetic efficiency is a consequence of energy distribution uniformity. The 3D results indicated the inefficient development of the electric field for low filling ratios. Thermal efficiencies higher than 90% were found for the higher loads and microwave efficiencies up to 75% were accomplished. The 80% fill ratio was demonstrated to be the optimal load with an associated global efficiency of 70%.

Keywords: multiphysics modeling, microwave heating, verification and validation, endothermic reactions modeling, impedance matching, limestone continuous processing

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Authors: Kuladip Jana, Bhaswati Banerjee, Parimal C. Sen

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Benzo(a)pyrene [B(a)P] is an environmental toxicant present mostly in cigarette smoke and car exhaust, is an aryl hydrocarbon receptor (AhR) ligand that exerts its toxic effects on both male and female reproductive systems along with carcinogenesis in skin, prostate, ovary, lung and mammary glands. Our study was focused on elucidating the molecular mechanism of B(a)P induced male reproductive toxicity and its prevention with phytochemical like resveratrol. In this study, the effect of B(a)P at different doses (0.1, 0.25, 0.5, 1 and 5 mg /kg body weight) was studied on male reproductive system of Wistar rat. A significant decrease in cauda epididymal sperm count and motility along with the presence of sperm head abnormalities and altered epididymal and testicular histology were documented following B(a)P treatment. B(a)P treatment resulted apoptotic sperm cells as observed by TUNEL and Annexin V-PI assay with increased Reactive Oxygen Species (ROS), altered sperm mitochondrial membrane potential (ΔΨm) with a simultaneous decrease in the activity of antioxidant enzymes and GSH status. TUNEL positive apoptotic cells also observed in testis as well as isolated germ and Leydig cells following B(a)P exposure. Western Blot analysis revealed the activation of p38 mitogen activated protein kinase (p38MAPK), cytosolic translocation of cytochrome-c, upregulation of Bax and inducible nitric oxide synthase (iNOS) with cleavage of poly ADP ribose polymerase (PARP) and down regulation of BCl2 in testis upon B(a)P treatment. The protein and mRNA levels of testicular key steroidogenesis regulatory proteins like steroidogenic acute regulatory protein (StAR), cytochrome P450 IIA1 (CYPIIA1), 3β hydroxy steroid dehydrogenase (3β HSD), 17β hydroxy steroid dehydrogenase (17β HSD) showed a significant decrease in a dose dependent manner while an increase in the expression of cytochrome P450 1A1 (CYP1A1), Aryl hydrocarbon Receptor (AhR), active caspase- 9 and caspase- 3 following B(a)P exposure. We conclude that exposure of benzo(a)pyrene caused testicular gamatogenic and steroidogenic disorders by induction of oxidative stress, inhibition of StAR and other steroidogenic enzymes along with activation of p38MAPK and initiated caspase-3 mediated germ and Leydig cell apoptosis. Next we investigated the role of resveratrol on B(a)P induced male reproductive toxicity. Our study highlighted that resveratrol co-treatment with B(a)P maintained testicular redox potential, increased serum testosterone level and prevented steroidogenic dysfunction with enhanced expression of major testicular steroidogenic proteins (CYPIIA1, StAR, 3β HSD,17β HSD) relative to treatment with B(a)P only. Resveratrol suppressed B(a)P-induced testicular activation of p38 MAPK, ATF2, iNOS and ROS production; cytosolic translocation of Cytochome c and Caspase 3 activation thereby prevented oxidative stress of testis and inhibited apoptosis. Resveratrol co-treatment also decreased B(a)P-induced AhR protein level, its nuclear translocation and subsequent CYP1A1 promoter activation, thereby decreased protein and mRNA levels of testicular cytochrome P4501A1 (CYP1A1) and prevented BPDE-DNA adduct formation. Our findings cumulatively suggest that resveratrol prevents activation of B(a)P by modulating the transcriptional regulation of CYP1A1 and acting as an antioxidant thus prevents B(a)P-induced oxidative stress and testicular apoptosis.

Keywords: benzo(a)pyrene, resveratrol, testis, apoptosis, cytochrome P450 1A1 (CYP1A1), aryl hydrocarbon receptor (AhR), p38 MAPK/ATF2/iNOS

Procedia PDF Downloads 197

Authors: Shreya Saxena, Felix Miller-Molloy, Phillipa Bowen, Greg Fellows, Elizabeth Bowen

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Background: Complex fluid balance abnormalities are well-established post-neurosurgery and traumatic brain injury (TBI). The triple-phase response requires fluid management strategies reactive to urine output and sodium homeostasis as patients shift between Diabetes Insipidus (DI) and Syndrome of Inappropriate ADH (SIADH). It was observed, at a tertiary paediatric center, a relatively high prevalence of the above complications within a cohort of paediatric post-neurosurgical and TBI patients. An audit of the clinical practice against set institutional guidelines was undertaken and analyzed to understand why this was occurring. Based on those results, new guidelines were developed with structured educational packages for the specialist teams involved. This was then reaudited, and the findings were compared. Methods: Two independent audits were conducted across two time periods, pre and post guideline change. Primary data was collected retrospectively, including both qualitative and quantitative data sets from the CQUIN neurosurgical database and electronic medical records. All paediatric patients post posterior fossa (PFT) or supratentorial surgery or with a TBI were included. A literature review of evidence-based practice, initial audit data, and stakeholder feedback was used to develop new clinical guidelines and nursing standard operation procedures. Compliance against these newly developed guidelines was re-assessed and a thematic, trend-based analysis of the two sets of results was conducted. Results: Audit-1 January2017-June2018, n=80; Audit-2 January2020-June2021, n=30 (reduced operative capacity due to COVID-19 pandemic). Overall, improvements in the monitoring of both fluid balance and electrolyte trends were demonstrated; 51% vs. 77% and 78% vs. 94%, respectively. The number of clear fluid management plans documented postoperatively also increased (odds ratio of 4), leading to earlier recognition and management of evolving fluid-balance abnormalities. The local paediatric endocrine team was involved in the care of all complex cases and notified sooner for those considered to be developing DI or SIADH (14% to 35%). However, significant Na fluctuations (>12mmol in 24 hours) remained similar – 5 vs six patients – found to be due to complex pituitary hypothalamic pathology – and the recommended adaptive fluid management strategy was still not always used. Qualitative data regarding useability and understanding of fluid-balance abnormalities and the revised guidelines were obtained from health professionals via surveys and discussion in the specialist teams providing care. The feedback highlighted the new guidelines provided a more consistent approach to the post-operative care of these patients and was a better platform for communication amongst the different specialist teams involved. The potential limitation to our study would be the small sample size on which to conduct formal analyses; however, this reflects the population that we were investigating, which we cannot control. Conclusion: The revised clinical guidelines, based on audited data, evidence-based literature review and stakeholder consultations, have demonstrated an improvement in understanding of the neuro-endocrine complications that are possible, as well as increased compliance to post-operative monitoring of fluid balance and electrolytes in this cohort of patients. Emphasis has been placed on preventative rather than treatment of DI and SIADH. Consequently, this has positively impacted patient safety for the center and highlighted the importance of educational awareness and multi-disciplinary team working.

Keywords: post-operative, fluid-balance management, neuro-endocrine complications, paediatric

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Authors: Davide Palma, Dimitra Papagiannaki, Marco Minella, Manuel Lai, Rita Binetti, Claire Richard

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Modern analytical technologies allow us to detect water contaminants at trace and ultra-trace concentrations highlighting how a large number of organic compounds is not efficiently abated by most wastewater treatment facilities relying on biological processes; we usually refer to these micropollutants as contaminants of emerging concern (CECs). The availability of reliable end effective technologies, able to guarantee the high standards of water quality demanded by legislators worldwide, has therefore become a primary need. In this context, water plasma stands out among developing technologies as it is extremely effective in the abatement of numerous classes of pollutants, cost-effective, and environmentally friendly. In this work, a custom-built non-thermal pulsed plasma discharge generator was used to abate the concentration of selected CECs in the water samples. Samples were treated in a 50 mL pyrex reactor using two different types of plasma discharge occurring at the surface of the treated solution or, underwater, working with positive polarity. The distance between the tips of the electrodes determined where the discharge was formed: underwater when the distance was < 2mm, at the water surface when the distance was > 2 mm. Peak voltage was in the 100-130kV range with typical current values of 20-40 A. The duration of the pulse was 500 ns, and the frequency of discharge could be manually set between 5 and 45 Hz. Treatment of 100 µM diclofenac solution in MilliQ water, with a pulse frequency of 17Hz, revealed that surface discharge was more efficient in the degradation of diclofenac that was no longer detectable after 6 minutes of treatment. Over 30 minutes were required to obtain the same results with underwater discharge. These results are justified by the higher rate of H₂O₂ formation (21.80 µmolL⁻¹min⁻¹ for surface discharge against 1.20 µmolL⁻¹min⁻¹ for underwater discharge), larger discharge volume and UV light emission, high rate of ozone and NOx production (up to 800 and 1400 ppb respectively) observed when working with surface discharge. Then, the surface discharge was used for the treatment of the three selected perfluoroalkyl compounds, namely, perfluorooctanoic acid (PFOA), perfluorohexanoic acid (PFHxA), and pefluorooctanesulfonic acid (PFOS) both individually and in mixture, in ultrapure and groundwater matrices with initial concentration of 1 ppb. In both matrices, PFOS exhibited the best degradation reaching complete removal after 30 min of treatment (degradation rate 0.107 min⁻¹ in ultrapure water and 0.0633 min⁻¹ in groundwater), while the degradation rate of PFOA and PFHxA was slower of around 65% and 80%, respectively. Total nitrogen (TN) measurements revealed levels up to 45 mgL⁻¹h⁻¹ in water samples treated with surface discharge, while, in analogous samples treated with underwater discharge, TN increase was 5 to 10 times lower. These results can be explained by the significant NOx concentrations (over 1400 ppb) measured above functioning reactor operating with superficial discharge; rapid NOx hydrolysis led to nitrates accumulation in the solution explaining the observed evolution of TN values. Ionic chromatography measures confirmed that the vast majority of TN was under the form of nitrates. In conclusion, non-thermal pulsed plasma discharge, obtained with a custom-built generator, was proven to effectively degrade diclofenac in water matrices confirming the potential interest of this technology for wastewater treatment. The surface discharge was proven to be more effective in CECs removal due to the high rate of formation of H₂O₂, ozone, reactive radical species, and strong UV light emission. Furthermore, nitrates enriched water obtained after treatment could be an interesting added-value product to be used as fertilizer in agriculture. Acknowledgment: This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 765860.

Keywords: CECs removal, nitrogen fixation, non-thermal plasma, water treatment

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Authors: Cory B. Portner, Julie A. Grauert, Lisa M. Stromme, Shelby D. Anderson, Franji H. Mayes

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Introduction: WASHINGTON state in the Pacific Northwest of the United States is internationally known for its technology industry, fisheries, agriculture, and vistas. On January 21, 2020, Washington state also became known as the first state with a confirmed COVID-19 case in the United States, thrusting the state into the international spotlight as the world came to grips with the global threat of this disease presented. Tourism is Washington state’s fourth-largest industry. Tourism to the state generates over 1.8 billion dollars (USD) in local and state tax revenue and employs over 180,000 people. Communicating with residents, stakeholders, and visitors on the status of disease activity, prevention measures, and response updates was vital to stopping the pandemic and increasing compliance and awareness. Significance: In order to communicate vital public health updates, guidance implementation, and safety measures to the public, the Washington State Department of Health established routine live virtual media briefings to reach audiences via social media, internet television, and broadcast television. Through close partnership with regional broadcast news stations and the state public affairs news network, the Washington State Department of Health hosted 95 media briefings from January 2020 through September 2022 and continues to regularly host live virtual media briefings to accommodate the needs of the public and media. Methods: Our methods quickly evolved from hosting briefings in the cement closet of a military base to being able to produce and stream the briefings live from any home-office location. The content was tailored to the hot topic of the day and to the reporter's questions and needs. Virtual media briefings hosted through inexpensive or free platforms online are extremely cost-effective: the only mandatory components are WiFi, a laptop, and a monitor. There is no longer a need for a fancy studio or expensive production software to achieve the goal of communicating credible, reliable information promptly. With minimal investment and a small learning curve, facilitators and panelists are able to host highly produced and engaging media availabilities from their living rooms. Results: The briefings quickly developed a reputation as the best source for local and national journalists to get the latest and most factually accurate information about the pandemic. In the height of the COVID-19 response, 135 unique media outlets logged on to participate in the briefing. The briefings typically featured 4-5 panelists, with as many as 9 experts in attendance to provide information and respond to media questions. Preparation was always a priority: Public Affairs staff for the Washington State Department of Health produced over 170 presenter remarks, including guidance on talking points for 63 expert guest panelists. Implication For Practice: Information is today’s most valuable currency. The ability to disseminate correct information urgently and on a wide scale is the most effective tool in crisis communication. Due to our role as the first state with a confirmed COVID-19 case, we were forced to develop the most accurate and effective way to get life-saving information to the public. The cost-effective, web-based methods we developed can be applied in any crisis to educate and protect communities under threat, ultimately saving lives from a laptop.

Keywords: crisis communications, public relations, media management, news media

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Authors: Hosein Maghsoudi

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Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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Authors: Brennan Lodge

Abstract:

Cybersecurity professionals have long been embroiled in a digital arms race, confronting increasingly sophisticated threats with innovative solutions. The field of cybersecurity is in an unending race against malicious adversaries. As threats evolve in complexity, the tools used to defend against them need to advance even faster. Burdened with a vast arsenal of tools and an expansive scope of threat intelligence, analysts frequently navigate a complex web, trying to discern patterns amidst information overload. Herein lies the potential of Retrieval Augmented Generation (RAG). By combining the capabilities of Large Language Models (LLMs) with a generative AI facet, RAG brings to the table an unparalleled ability for real-time cross-referencing, bridging the gap between raw data and actionable insights. Imagine an analyst named Sarah working at a global Fortune 500 company. Every day, Sarah navigates a maze of diverse knowledge bases, real-time threat intelligence, and her company's vast proprietary data, from network specifics to intricate technical blueprints. One day, she's challenged by a potential breach through a personal device due to the company's global "Bring Your Own Device" policy. With the clock ticking, Sarah has mere minutes to trace the malware's origin, all while considering complex regional regulations. As she races against the benchmark of Mean Time To Resolution (MTTR), she wonders: Could "Cozy Bear" with its notorious malware tactic, HAMMERTOSS, be behind this? Balancing policy intricacies, global network considerations, and ever-emerging cyber threats, Sarah's role epitomizes the intense challenges faced by today's cybersecurity analysts. While analysts grapple with this array of intricate, time-sensitive challenges, the necessity for precision and efficiency is key. RAG technology—a cutting-edge advancement in Gen AI—is a promising solution. Designed to assimilate diverse data sources such as cyber advisory notices, phishing email sentiment, secure and insecure code examples, information security policy documentation, and the MITRE ATT&CK framework, RAG equips analysts with real-time querying capabilities through a vector database and a cross referenced concise response from a Gen AI model. Traditional relational databases often necessitate a tedious process of filtering through numerous entries. Now, with the synergy of vector databases and Gen AI models, analysts can rapidly access both contextually or semantically akin data points. This augmented approach equips analysts with a comprehensive understanding of the prevailing cyber threats, elevating the robustness of cybersecurity defenses and upskilling the analyst and team, too. Vector databases underpin the knowledge translation in Gen AI. They bridge the gap between raw data and translation into meaningful insights, ensuring that analysts are equipped with comprehensive and relevant information. This superior capability of the RAG framework, with its impressive depth and precision, finds application across a broad spectrum of cybersecurity challenges. Let's delve into some use cases where its potential becomes particularly evident: Phishing Email Sentiment Analysis: Phishing remains a predominant vector for cybersecurity breaches. Leveraging RAG's capabilities, analysts can not only assess the potential malevolence of an email but can also understand the context behind it. By cross-referencing patterns from varied data sources in real-time, the detection process evolves from a mere content evaluation to a holistic understanding of attacker tactics, behaviors, and evolving profiles. This allows for the identification of nuanced phishing strategies that might otherwise go undetected. Insecure Code Analysis: Software vulnerabilities form a critical entry point for cyber adversaries. With RAG, the process of code evaluation undergoes a transformation. Instead of manual code reviews, the system pulls insights from vector databases and historical code snippets marked as insecure, enabling detection of vulnerabilities based on historical patterns, emerging threat vectors, and even predictive threat modeling. This ensures that even the most obfuscated or embedded vulnerabilities are identified, and corrective measures can be promptly implemented. Vulnerability and Upskill Advisory: In the fast-paced world of cybersecurity, staying updated is paramount. Through RAG's capabilities, analysts are not only made aware of real-time vulnerabilities but are also guided on the necessary skills and tools needed to combat them. By dynamically sourcing data through vulnerability advisories, news on advanced persistent threats, and tactics to defend, RAG ensures that analysts are not only reactive to threats but are also proactively upskilled, thereby bolstering their defense mechanisms. Information Security Policies for Compliance Teams: Compliance remains at the heart of many organizational cybersecurity strategies. However, with ever-shifting regulatory landscapes, staying compliant becomes a moving target. RAG's ability to source real-time data ensures that compliance teams always have access to the latest policy changes, guidelines, and best practices. This not only facilitates adherence to current standards but also anticipates future shifts, assists with audits, and ensures that organizations remain ahead of the compliance curve. Fusing a RAG architecture with platforms like Slack amplifies its practical utility. Slack, known for its real-time communication prowess, seamlessly evolves into more than just a messaging platform in this context. Cybersecurity analysts can pose intricate queries within Slack and, almost instantaneously, receive comprehensive feedback powered by the harmonious interplay of RAG and Gen AI. This integration effectively transforms Slack into an AI-augmented chatbot-like assistant for cybersecurity professionals, always ready to provide informed insights on-demand, making it an indispensable ally in the ever-evolving cyber battlefield. Navigating the vast landscape of cybersecurity, analysts often encounter unfamiliar terminologies and techniques., analysts require tools that not only detect or inform them of threats, like CISA (U.S Cybersecurity Infrastructure Security Agency) Advisories, but also interpret and communicate them effectively. Consider a junior cybersecurity analyst named Alex, who comes across the term "Kerberoasting" while reviewing a network log. Unfamiliar with its intricacies, Alex turns to Slack to pose a query: "chat explain is Kerberoasting, using CISA." Almost instantaneously, Slack, powered by the harmonious interplay of RAG and Gen AI, provides a detailed response, cross-referencing a recent cyber advisory on the technique. It explains how attackers can exploit the Kerberos Ticket Granting Service to decipher service account passwords, potentially compromising a network. In this dynamic realm of cybersecurity, the blend of RAG and Generative AI represents more than just a technological leap. It embodies a paradigm shift, promising a future where human expertise and AI-driven precision join forces. As cyber threats continue their relentless advance, this synergy ensures that defenders are equipped with an arsenal that's not just reactive, but also profoundly insightful. No longer should analysts be submerged in a deluge of data without direction. Instead, they should be empowered, to discern, act, and preempt with unparalleled clarity and confidence. By harmoniously intertwining human discernment with AI capabilities, we should chart a path towards a future where cybersecurity is not just about defense, but about achieving a strategic advantage, paving the way for a safer, informed and a more secure digital horizon.

Keywords: cybersecurity, gen AI, retrieval augmented generation, cybersecurity defense strategies

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