Search results for: proton pump inhibitors

Authors: Zakia Belhadj, Bing He, Hua Zhang, Xueqing Wang, Wenbing Dai, Qiang Zhang

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Mononuclear phagocyte system (MPS) forms an abominable obstacle hampering the tumor delivery efficiency of nanoparticles. Passively targeted nanocarriers have received clinical approval over the past 20 years. However, none of the actively targeted nanocarriers have entered clinical trials. Thus it is important to endue effective targeting ability to actively targeted approaches by overcoming biological barriers to nanoparticle drug delivery. Here, it presents that an Esomeprazole-based preconditioning strategy for regulating nanocarrier-MPS interaction to substantially prolong circulation time and enhance tumor targeting of nanoparticles. In vitro, the clinically approved proton pump inhibitor Esomeprazole “ESO” was demonstrated to reduce interactions between macrophages and subsequently injected targeted vesicles by interfering with their lysosomal trafficking. Of note, in vivo studies demonstrated that ESO pretreatment greatly decreased the liver and spleen uptake of c(RGDm7)-modified vesicles, highly enhanced their tumor accumulation, thereby provided superior therapeutic efficacy of c(RGDm7)-modified vesicles co-loaded with Doxorubicin (DOX) and Gefitinib (GE). This MPS-preconditioning strategy using ESO provides deeper insights into regulating nanoparticles interaction with the phagocytic system and enhancing their cancer cells' accessibility for anticancer therapy.

Keywords: esomeprazole (ESO), mononuclear phagocyte system (MPS), preconditioning strategy, targeted lipid vesicles

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Authors: Maryam Panahi

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Background: Adjuvants such as ketamine, promethazine, and paracetamol could bring up patient's satisfaction and control the harmful effects of opioids besides lessening their needed doses, as seen by the fentanyl/paracetamol and fentanyl/ketamine combination before. The current study is headed to compare paracetamol and ketamine, in addition to fentanyl, applied by infusion pumps in order to pain relief following major surgery. Materials and Methods: Through a double-blinded, randomized clinical trial, patients between18 and 65 with elective surgery for tight or leg fractures with ASA Class 1 and 2 referred to a university hospital in Arak, a town in the central region of Iran, were recruited and used infusion pump for their postoperative pain control. The participants were divided into cases and controls regarding using ketamine/fentanyl (KF) or paracetamol/fentanyl (PF) infusion pumps. Results: The mean pain score was a total of 3.87, with the highest value in KF (5.06) and the lowest in PF (4.50) immediately after finishing the surgery and getting conscious when started using an infusion pump. There was no statistical difference between the groups in this regard. Concerning the side effects of the applied medications, blood pressure and heart rate had no differences comparing the groups. Conclusion: This study showed that paracetamol used in infusion pumps could be brilliant in pain control after major surgeries like those done in lower extremities and joint replacement while lessening opioid use. Although paracetamol was more effective than ketamine in the current trial, more qualified studies at bigger sizes and in other fields of surgery besides orthopedic ones would be useful to support the effects if applicable

Keywords: infusion pump, Ketamine, Paracetamol, pain

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Authors: B.S. Roopa

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Objectives: To investigate the prevalence of concomitant use of GPDs in patients treated with NSAIDs and GPDs in recommended dose and frequency as prophylaxis. And also to know the association between risk factors and prescription of GPDs in patients treated with NSAIDs. Methods: Study was a prospective, observational, cross-sectional survey. Data from patients with prescription of NSAIDs at the out-patient departments of secondary care Hospital, Nilgiris, India were collected in a specially designed proforma for a period of 45 days. Analysis using χ2 tests for discrete variables. Factors that might be associated with prescription of GPD with NSIADs were assessed in multiple logistic regression models. Results: Three hundred and three patients were included in this study, and the rate of GPD prescription was 89.1%. Most of the patients received H2-receptor antagonist, and, to a lesser degree, antacid and proton pump inhibitor. Patients with history of GI ulcer/bleeding were much more likely to be co-prescribed GPD than those who had no history of GI disorders .Compared with patients who were managed in general outpatient clinic, those managed in Secondary care hospital in Nilgrisis, India were more likely to receive GPD. Conclusions: The prescription rate of GPD with NSAIDs is high. Patients were prescribed with H2RA with dose of 150mg twice daily, which are not effective in reducing the risk of NSAIDs induced gastric ulcer. Only the frequency of NSAIDs prescription was considered significant determinant for the co-prescription with GPAs in patients who are < 65 years and ≥ 65 years old.

Keywords: gastro protective agents, non steridol anti inlfammatory agents

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Authors: Ayman A. Al Hayek, Asirvatham A. Robert, Mohamed A. Al Dawish, Rim B. Braham, Hanouf S. Goudeh, Fahad S. Al Sabaan

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Introduction: The aim of this study was to explore the impact of insulin pump therapy on diabetes treatment satisfaction and glycemic control among patients with type 1 diabetes mellitus (T1DM) in Saudi Arabia. Methods: A 6-month, prospective study was conducted among 47 patients (aged17–24 years) with T1DM who attended the Insulin Pump Clinic at Prince Sultan Military Medical City, Riyadh, Saudi Arabia, between April 2014 and November 2014. The respondents were purposively and conveniently selected and were interviewed using the Arabic version of the Diabetes Treatment Satisfaction Questionnaire at baseline, 3, and 6 months. Demographics and clinical variables including hemoglobin A1c (HbA1c) were also collected. Results: The mean (±standard deviation) age of the study cohort was 19.1 ± 1.93 years. Seventeen patients were male (36.2%) and 30 were female (63.8%). Compared to baseline, significant positive differences were found in treatment satisfaction among female patients and patients with long-standing T1DM at 6 months. Frequency of hyperglycemia and hypoglycemia declined significantly in female patient’s at 6 months and in patients who had a shorter duration of T1DM. Furthermore, significant positive differences were found in HbA1c levels among female patients and among those who had a shorter duration of T1DM compared to baseline. Both female and male patients and those with a shorter duration of T1DM showed significant decline in insulin necessity at6months when compared to baseline. Conclusion: Although multiple daily injections is a feasible preference for insulin supply, insulin pumps should also be considered for patients with T1DM as it appears to increase patients’ treatment satisfaction, decrease the frequency of hypoglycemia, hyperglycemia, and reduce HbA1c levels.

Keywords: type 1 diabetes, insulin pump, Saudi Arabia, T1DM

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Authors: Yazan M. Alatrash, Han-ok Kang, Hyun-gi Yoon, Shen Zhang, Juhyeon Yoon

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Flow coastdown phenomena are very important to secure nuclear fuel integrity during loss of off-site power accidents. In this study, primary coolant flow coastdown phenomena are investigated for the Jordan Research and Training Reactor (JRTR) using a simulation software package, Modular Modelling System (MMS). Two MMS models are built. The first one is a simple model to investigate the characteristics of the primary coolant pump only. The second one is a model for a simulation of the Primary Coolant System (PCS) loop, in which all the detailed design data of the JRTR PCS system are modelled, including the geometrical arrangement data. The same design data for a PCS pump are used for both models. Coastdown curves obtained from the two models are compared to study the PCS loop coolant inertia effect on a flow coastdown. Results showed that the loop coolant inertia effect is found to be small in the JRTR PCS loop, i.e., about one second increases in a coastdown half time required to halve the coolant flow rate. The effects of different flywheel inertia on the flow coastdown are also investigated. It is demonstrated that the coastdown half time increases with the flywheel inertia linearly. The designed coastdown half time is proved to be well above the design requirement for the fuel integrity.

Keywords: flow coastdown, loop inertia, modelling, research reactor

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Authors: Eman Alzahrani, Hala M. Abo-Dief, Ashraf T. Mohamed

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The present work is aimed at examining carbon steel oil pipelines corrosion using three natural extracts (Eruca Sativa, Rosell and Mango peels) that are used as inhibitors of different concentrations ranging from 0.05-0.1wt. %. Two sulphur compounds are used as corrosion mediums. Weight loss method was used for measuring the corrosion rate of the carbon steel specimens immersed in technical white oil at 100ºC at various time intervals in absence and presence of the two sulphur compounds. The corroded specimens are examined using the chemical wear test, scratch test and hardness test. The scratch test is carried out using scratch loads from 0.5 Kg to 2.0 Kg. The scratch width is obtained at various scratch load and test conditions. The Brinell hardness test is carried out and investigated for both corroded and inhibited specimens. The results showed that three natural extracts can be used as environmentally friendly corrosion inhibitors.

Keywords: inhibition, natural extract, oil pipelines corrosion, sulphur compounds

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Authors: Wanru Huang, Fujun Wang, Chaoyue Wang, Yuan Tang, Zhifeng Yao, Ruofu Xiao, Xin Chen

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Rotating stall in centrifugal pump is an unsteady flow phenomenon that causes instabilities and high hydraulic losses. It typically occurs at low flow rates due to large flow separation in impeller blade passage. In order to reveal the influence of incoming flow conditions on rotating stall in centrifugal pump, a numerical method for investigating rotating stall was established. This method is based on a modified SST k-ω turbulence model and a fine mesh model was adopted. The calculated flow velocity in impeller by this method was in good agreement with PIV results. The effects of flow rate and sealing-ring leakage on stall characteristics of centrifugal pump were studied by using the proposed numerical approach. The flow structures in impeller under typical flow rates and typical sealing-ring leakages were analyzed. It is found that the stall vortex frequency and circumferential propagation velocity increase as flow rate decreases. With the flow rate decreases from 0.40Qd to 0.30Qd, the stall vortex frequency increases from 1.50Hz to 2.34Hz, the circumferential propagation velocity of the stall vortex increases from 3.14rad/s to 4.90rad/s. Under almost all flow rate conditions where rotating stall is present, there is low frequency of pressure pulsation between 0Hz-5Hz. The corresponding pressure pulsation amplitude increases with flow rate decreases. Taking the measuring point at the leading edge of the blade pressure surface as an example, the flow rate decreases from 0.40Qd to 0.30Qd, the pressure fluctuation amplitude increases by 86.9%. With the increase of leakage, the flow structure in the impeller becomes more complex, and the 8-shaped stall vortex is no longer stable. On the basis of the 8-shaped stall vortex, new vortex nuclei are constantly generated and fused with the original vortex nuclei under large leakage. The upstream and downstream vortex structures of the 8-shaped stall vortex have different degrees of swimming in the flow passage, and the downstream vortex swimming is more obvious. The results show that the proposed numerical approach could capture the detail vortex characteristics, and the incoming flow conditions have significant effects on the stall vortex in centrifugal pumps.

Keywords: centrifugal pump, rotating stall, numerical simulation, flow condition, vortex frequency

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Authors: Dong Liu

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By sending a high-frequency probe wave and a low-frequency pump wave to a specimen, the vibroacoustic method evaluates the defect’s severity according to the modulation index of the received signal. Many studies experimentally proved the significant sensitivity of the modulation index to the tiny contact type defect. However, it has also been found that the modulation index was highly affected by the frequency of probe or pump waves. Therefore, the chirp signal has been introduced to the VAM method since it can assess multiple frequencies in a relatively short time duration, so the robustness of the VAM method could be enhanced. Consequently, the signal processing method needs to be modified accordingly. Various studies utilized different algorithms or combinations of algorithms for processing the VAM signal method by chirp excitation. These signal process methods were compared and used for processing a VAM signal acquired from the steel samples.

Keywords: vibroacoustic modulation, nonlinear acoustic modulation, nonlinear acoustic NDT&E, signal processing, structural health monitoring

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Authors: Aysun Sezer

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Magnetic Resonance Imaging (MRI) is one of the advanced diagnostic tools for evaluating shoulder pathologies. Proton Density (PD)-weighted MRI sequences prove highly effective in detecting edema. However, they are deficient in the anatomical identification of bones due to a trauma-induced decrease in signal-to-noise ratio and blur in the traumatized cortices. Computer-based diagnostic systems require precise segmentation, identification, and localization of anatomical regions in medical imagery. Deep learning-based object detection algorithms exhibit remarkable proficiency in real-time object identification and localization. In this study, the YOLOv8 model was employed to detect humeral head and scapular regions in 665 axial PD-weighted MR images. The YOLOv8 configuration achieved an overall success rate of 99.60% and 89.90% for detecting the humeral head and scapula, respectively, with an intersection over union (IoU) of 0.5. Our findings indicate a significant promise of employing YOLOv8-based detection for the humerus and scapula regions, particularly in the context of PD-weighted images affected by both noise and intensity inhomogeneity.

Keywords: YOLOv8, object detection, humerus, scapula, IRM

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Authors: Nigar Kantarci Carsibasi

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Coarse-grained elastic network models, namely Gaussian network model (GNM) and Anisotropic network model (ANM), are utilized in order to investigate the fluctuation dynamics of Murine Double Minute 2 (MDM2), which is the native inhibitor of p53. Conformational dynamics of MDM2 are elucidated in unbound, p53 bound, and non-peptide small molecule inhibitor bound forms. With this, it is aimed to gain insights about the alterations brought to global dynamics of MDM2 by native peptide inhibitor p53, and two small molecule inhibitors (HDM201 and NVP-CGM097) that are undergoing clinical stages in cancer studies. MDM2 undergoes significant conformational changes upon inhibitor binding, carrying pieces of evidence of induced-fit mechanism. Small molecule inhibitors examined in this work exhibit similar fluctuation dynamics and characteristic mode shapes with p53 when complexed with MDM2, which would shed light on the design of novel small molecule inhibitors for cancer therapy. The results showed that residues Phe 19, Trp 23, Leu 26 reside in the minima of slowest modes of p53, pointing to the accepted three-finger binding model. Pro 27 displays the most significant hinge present in p53 and comes out to be another functionally important residue. Three distinct regions are identified in MDM2, for which significant conformational changes are observed upon binding. Regions I (residues 50-77) and III (residues 90-105) correspond to the binding interface of MDM2, including (α2, L2, and α4), which are stabilized during complex formation. Region II (residues 77-90) exhibits a large amplitude motion, being highly flexible, both in the absence and presence of p53 or other inhibitors. MDM2 exhibits a scattered profile in the fastest modes of motion, while binding of p53 and inhibitors puts restraints on MDM2 domains, clearly distinguishing the kinetically hot regions. Mode shape analysis revealed that the α4 domain controls the size of the cleft by keeping the cleft narrow in unbound MDM2; and open in the bound states for proper penetration and binding of p53 and inhibitors, which points to the induced-fit mechanism of p53 binding. P53 interacts with α2 and α4 in a synchronized manner. Collective modes are shifted upon inhibitor binding, i.e., second mode characteristic motion in MDM2-p53 complex is observed in the first mode of apo MDM2; however, apo and bound MDM2 exhibits similar features in the softest modes pointing to pre-existing modes facilitating the ligand binding. Although much higher amplitude motions are attained in the presence of non-peptide small molecule inhibitor molecules as compared to p53, they demonstrate close similarity. Hence, NVP-CGM097 and HDM201 succeed in mimicking the p53 behavior well. Elucidating how drug candidates alter the MDM2 global and conformational dynamics would shed light on the rational design of novel anticancer drugs.

Keywords: cancer, drug design, elastic network model, MDM2

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Authors: Jung-Feng Hsieh, Chu Ze Chen

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Curcumin is the main active compound of turmeric that can inhibit the activities of α-glucosidase and xanthine oxidase (XO). α-Glucosidase and XO inhibitors are widely used to treat patients with diabetes mellitus and gout, respectively; therefore, the objective of this research was to evaluate the inhibitory activities of curcumin and its analogs against α-glucosidase and XO. Our results demonstrated that CM-F had the strongest antioxidant activity with a half-maximal effective concentration (EC50) of 9.39 ± 0.16 μM, which was superior to vitamin E (EC50=17.03 ± 0.09 μM). CM-F also exhibited potent inhibitory activity against XO with an IC50 value of 6.14 ± 0.38 μM and enzyme kinetic results revealed competitive inhibition of XO. We also found that CM-1 and CM-2 inhibited α-glucosidase with IC50 values of 21.06 ± 0.92 μM and 5.95 ± 0.09 μM, respectively, and kinetic studies indicated that both CM-1 and CM-2 are mixed competitive inhibitors of α-glucosidase. Furthermore, docking simulation identified five hydrogen bonds between XO and CM-F; however, only one and two hydrogen bonds are involved in CM-1 and CM-2 binding to α-glucosidase, respectively. Accordingly, curcumin and its analogs have the potential to be used in the treatment of patients with diabetes mellitus and gout.

Keywords: curcumin, α-glucosidase, inhibitor, xanthine oxidase

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Authors: B. Dehghan, T. Toppi, M. Aprile, M. Motta

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The environmental concerns related to global warming and ozone layer depletion along with the growing worldwide demand for heating and cooling have brought an increasing attention toward ecological and efficient Heating, Ventilation, and Air Conditioning (HVAC) systems. Furthermore, since space heating accounts for a considerable part of the European primary/final energy use, it has been identified as one of the sectors with the most challenging targets in energy use reduction. Heat pumps are commonly considered as a technology able to contribute to the achievement of the targets. Current research focuses on the full load operation and seasonal performance assessment of three gas-driven absorption heat pump cycles. To do this, investigations of the gas-driven air-source ammonia-water absorption heat pump systems for small-scale space heating applications are presented. For each of the presented cycles, both full-load under various temperature conditions and seasonal performances are predicted by means of numerical simulations. It has been considered that small capacity appliances are usually equipped with fixed geometry restrictors, meaning that the solution mass flow rate is driven by the pressure difference across the associated restrictor valve. Results show that gas utilization efficiency (GUE) of the cycles varies between 1.2 and 1.7 for both full and partial loads and vapor exchange (VX) cycle is found to achieve the highest efficiency. It is noticed that, for typical space heating applications, heat pumps operate over a wide range of capacities and thermal lifts. Thus, partially, the novelty introduced in the paper is the investigation based on a seasonal performance approach, following the method prescribed in a recent European standard (EN 12309). The overall result is a modest variation in the seasonal performance for analyzed cycles, from 1.427 (single-effect) to 1.493 (vapor-exchange).

Keywords: absorption cycles, gas utilization efficiency, heat pump, seasonal performance, vapor exchange cycle

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Authors: Yanqin Chen, Chao Jiang, Chongdu Cho

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This research presents the three-dimensional mechanical characteristics of a commercial gas diffusion layer by experiment and simulation results. Although the mechanical performance of gas diffusion layers has attracted much attention, its reliability and accuracy are still a major challenge. With the help of simulation analysis methods, it is beneficial to the gas diffusion layer’s extensive commercial development and the overall stress analysis of proton electrolyte membrane fuel cells during its pre-production design period. Therefore, in this paper, a three-dimensional constitutive model of a commercial gas diffusion layer, including its material stiffness matrix parameters, is developed and coded, in the user-defined material model of a commercial finite element method software for simulation. Then, the model is validated by comparing experimental results as well as simulation outcomes. As a result, both the experimental data and simulation results show a good agreement with each other, with high accuracy.

Keywords: gas diffusion layer, proton electrolyte membrane fuel cell, stiffness matrix, three-dimensional mechanical characteristics, user-defined material model

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Authors: Bhuvanesh Baniya

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Alzheimer disease is illnesses that are responsible for neuronal cell death and resulting in lifelong cognitive problems. Due to their unclear mechanism, there are no effective drugs available for the treatment. For a long time, herbal drugs have been used as a role model in the field of the drug discovery process. Holy basil in the Indian medicinal system (Ayurveda) is used for several neuronal disorders like insomnia and memory loss for decades. This study aims to identify active components of holy basil as potential inhibitors for the treatment of Alzheimer disease. To fulfill this objective, the Network pharmacology approach, gene ontology, pharmacokinetics analysis, molecular docking, and molecular dynamics simulation (MDS) studies were performed. A total of 7 active components in holy basil, 12 predicted neurodegenerative targets of holy basil, and 8063 Alzheimer-related targets were identified from different databases. The network analysis showed that the top ten targets APP, EGFR, MAPK1, ESR1, HSPA4, PRKCD, MAPK3, ABL1, JUN, and GSK3B were found as significant target related to Alzheimer disease. On the basis of gene ontology and topology analysis results, APP was found as a significant target related to Alzheimer’s disease pathways. Further, the molecular docking results to found that various compounds showed the best binding affinities. Further, MDS top results suggested could be used as potential inhibitors against APP protein and could be useful for the treatment of Alzheimer’s disease.

Keywords: holy basil, network pharmacology, neurodegeneration, active phytochemicals, molecular docking and simulation

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Authors: Rui-Xiong Han, Rui Ge, Shao-Peng Li, Lin Bian, Liang-Rui Sun, Min-Jing Sang, Rui Ye, Ya-Ping Liu, Xiang-Zhen Zhang, Jie-Hao Zhang, Zhuo Zhang, Jian-Qing Zhang, Miao-Fu Xu

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The Chinese Accelerator Driven Sub-critical system (C-ADS) uses a high-energy proton beam to bombard the metal target and generate neutrons to deal with the nuclear waste. The Chinese ADS proton linear has two 0~10 MeV injectors and one 10~1500 MeV superconducting linac. Injector-I is studied by the Institute of High Energy Physics (IHEP) under construction in the Beijing, China. The linear accelerator consists of two accelerating cryomodules operating at the temperature of 2 Kelvin. This paper describes the structure and thermal performances analysis of the cryomodule. The analysis takes into account all the main contributors (support posts, multilayer insulation, current leads, power couplers, and cavities) to the static and dynamic heat load at various cryogenic temperature levels. The thermal simulation analysis of the cryomodule is important theory foundation of optimization and commissioning.

Keywords: C-ADS, cryomodule, structure, thermal simulation, static heat load, dynamic heat load

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Authors: Paweł Stączek, Tomasz Plech, Aleksandra Strzelczyk, Katarzyna Dzitko, Monika Wujec, Edyta Kuśmierz, Piotr Paneth, Agata Paneth

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In this contribution, we will describe the inhibitory potency of nine thiosemicarbazide derivatives against bacterial type IIA topoisomerases, their antibacterial profile, and molecular modeling evaluation. We have found that one of the tested compounds, 4-benzoyl-1-(2-methyl-furan-3-ylcarbonyl) thiosemicarbazide, remarkably inhibits the activity of S. aureus DNA gyrase with the IC50 below 5 μM. Besides, this compound displays antibacterial activity on Staphylococcus spp. and E. faecalis at non-cytotoxic concentrations in mammalian cells, with minimal inhibitory concentrations (MICs) values at 25 μg/mL. Based on the enzymatic and molecular modeling studies we propose two factors, i.e. geometry of molecule and hydrophobic/hydrophilic balance as important molecular properties for developing thiosemicarbazide derivatives as potent Staphylococcus aureus DNA gyrase inhibitors.

Keywords: bioactivity, drug design, topoisomerase, molecular modeling

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Authors: Nashwa A. Mohamed

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Introduction: Omeprazole is a proton pump inhibitor used commonly in the treatment of acid-peptic disorders. Although omeprazole is generally well tolerated, serious adverse effects such as renal failure have been reported. Ginger is an antioxidant that could play a protective role in models of experimentally induced nephropathies. Aim of the work: The aim of this work was to study the possible histological changes induced by omeprazole on renal cortex and evaluate the possible protective effect of ginger on omeprazole-induced renal damage in adult male albino rats. Materials and methods: Twenty-four adult male albino rats divided into four groups (six rats each) were used in this study. Group I served as the control group. Rats of group II received only an aqueous extract of ginger daily for 3 months through a gastric tube. Rats of group III were received omeprazole orally through a gastric tube for 3 months. Rats of group IV were given both ginger and omeprazole at the same doses and through the same routes as the previous two groups. At the end of the experiment, the rats were sacrificed. Renal tissue samples were processed for light, immunohistochemical and electron microscopic examination. The obtained results were analysed morphometrically and statistically. Results: Omeprazole caused several histological changes in the form of loss of normal appearance of renal cortex with degenerative changes in the renal corpuscle and tubules. Cellular infilteration was also observed. The filteration barrier was markedly affected. Ginger ameliorated the omeprazole-induced histological changes. Conclusion: Omeprazole induced injurious effects on renal cortex. Coadministration of ginger can ameliorate the histological changes induced by omeprazole.

Keywords: ginger, kidney, omeprazole, rat

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Authors: Tomasz Frączek, Agata Paneth, Rafał Kamiński, Agnieszka Krakowiak, Piotr Paneth

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Azoles are a promising class of the new generation of HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs). From thousands of reported compounds, many possess the same basic structure of an aryl substituted azole ring linked by a thioglycolamide chain with another aromatic ring. To find novel extensions for this primary scaffold, we explored the 5-position substitution of triazole NNRTIs using molecular docking followed by synthesis of selected compounds. We discovered that heterocyclic substituents in 5-position of the triazole ring are detrimental to the inhibitory activity of compounds with 4-membered thioglycolamide linker. This substitution seems to be viable only for compounds with a shorter 2-membered linker such as in derivatives of 4‐benzyl‐3‐(benzyl-sulfanyl)‐5‐(thiophen‐2‐yl)‐4H‐1,2,4‐triazole reported earlier. A new scaffold of 2‐[(4‐benzyl‐5‐methyl‐4H‐1,2,4‐triazol‐3‐yl)sulfanyl]‐N‐phenylacetamide has been identified in this study.

Keywords: docking, molecular modeling, drug design, novel scaffolds

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Authors: Tarcisio F. Leao, Bruno Utiyama, Jeison Fonseca, Eduardo Bock, Aron Andrade

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This work presents a blood flow estimator based in Look-Up-Table (LUT) for control of Left Ventricular Assist Device (LVAD). This device has been used as bridge to transplantation or as destination therapy to treat patients with heart failure (HF). Destination Therapy application requires a high performance LVAD; thus, a stable control is important to keep adequate interaction between heart and device. LVAD control provides an adequate cardiac output while sustaining an appropriate flow and pressure blood perfusion, also described as physiologic control. Because thrombus formation and system reliability reduction, sensors are not desirable to measure these variables (flow and pressure blood). To achieve this, control systems have been researched to estimate blood flow. LVAD used in the study is composed by blood centrifugal pump, control, and power supply. This technique used pump and actuator (motor) parameters of LVAD, such as speed and electric current. Estimator relates electromechanical torque (motor or actuator) and hydraulic power (blood pump) via LUT. An in vitro Mock Loop was used to evaluate deviations between blood flow estimated and actual. A solution with glycerin (50%) and water was used to simulate the blood viscosity with hematocrit 45%. Tests were carried out with variation hematocrit: 25%, 45% and 58% of hematocrit, or 40%, 50% and 60% of glycerin in water solution, respectively. Test with bovine blood was carried out (42% hematocrit). Mock Loop is composed: reservoir, tubes, pressure and flow sensors, and fluid (or blood), beyond LVAD. Estimator based in LUT is patented, number BR1020160068363, in Brazil. Mean deviation is 0.23 ± 0.07 L/min for mean flow estimated. Larger mean deviation was 0.5 L/min considering hematocrit variation. This estimator achieved deviation adequate for physiologic control implementation. Future works will evaluate flow estimation performance in control system of LVAD.

Keywords: blood pump, flow estimator, left ventricular assist device, look-up-table

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Authors: Joshua Chew, Vesa Cheng, David Thomson

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Background: Hereditary angioedema (HAE) or C1 esterase deficiency is a relatively rare entity that has a potential for significant anesthetic complications. Methods: A literature review was performed of published cases of surgery in patients with HAE. Results were limited to English language only and cases were examined for management strategies and successful prevention of acute attacks. Results: The literature revealed the successful use of C1 esterase inhibitors as the most common agent in surgical prophylaxis therapy. Other therapeutic targets described included kallikrein inhibitors and bradykinin B2 receptor antagonists. Conclusions: Therapeutic targets that exist for the management of acute attacks in HAE have been successfully employed in the setting of surgery. The data is currently limited and could not be used as a firm evidence base, but the limited outcomes seen are positive and reassuring for the prospective anesthetic management of this potentially fatal condition.

Keywords: anesthesia, C1 esterase deficiency, hereditary angioedema, surgical prophylaxis

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Authors: Filipa Vasconcelos

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The administration of endoplasmic reticulum amino peptidases (ERAP1 or ERAP2) inhibitors can be used for therapeutic approaches against cancer and auto-immune diseases. However, one of the main shortcomings of drug delivery systems (DDS) is associated with the drug off-target distribution, which can lead to an increase in its side effects on the patient’s body. To overcome such limitations, the encapsulation of four representative compounds of ERAP inhibitors into Polycaprolactone (PCL), Polyvinyl-alcohol (PVA), crosslinked PVA, and PVA with nanoparticles (liposomes) electrospun fibrous meshes is proposed as a safe and controlled drug release system. The use of electrospun fibrous meshes as a DDS allows efficient solvent evaporation giving limited time to the encapsulated drug to recrystallize, continuous delivery of the drug while the fibers degrade, prevention of initial burst release (sustained release), tunable dosages, and the encapsulation of other agents. This is possible due to the fibers' small diameters and resemblance to the extracellular matrix (confirmed by scanning electron microscopy results), high specific surface area, and good mechanical strength/stability. Furthermore, release studies conducted on PCL, PVA, crosslinked PVA, and PVA with nanoparticles (liposomes) electrospun fibrous meshes with each of the ERAP compounds encapsulated demonstrated that they were capable of releasing >60%, 50%, 40%, and 45% of the total ERAP concentration, respectively. Fibrous meshes with ERAP_E compound encapsulated achieved higher released concentrations (75.65%, 62.41%, 56.05%, and 65.39%, respectively). Toxicity studies of fibrous meshes with encapsulated compounds are currently being accessed in vitro, as well as pharmacokinetics and dynamics studies. The last step includes the implantation of the drug-loaded fibrous meshes in vivo.

Keywords: drug delivery, electrospinning, ERAP inhibitors, liposomes

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Authors: Mohamed Hassan Gundu, Jaeseung Lee, Muhammad Faizan Chinannai, Hyunchul Ju

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In this study, we present the effects of bipolar plate design to control the temperature of the cell and ensure effective water management under an excessive amount of air flow and low humidification conditions in the proton exchange membrane fuel cell (PEMFC). The PEMFC model developed and applied to consider a three type of bipolar plate that is defined by ratio of inlet channel width to outlet channel width. Simulation results show that the design which has narrow gas inlet channel and wide gas outlet channel width (wide coolant inlet channel and narrow coolant outlet channel width) make the relative humidity and water concentration increase in the channel and the catalyst layer. Therefore, this study clearly demonstrates that the dehydration phenomenon can be decreased by using design of bipolar plate with narrow gas inlet channel and wide gas outlet channel width (wide coolant inlet channel and narrow coolant outlet channel width).

Keywords: PEMFC, air-cooling, relative humidity, water management, water concentration, oxygen concentration

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Authors: Esma Kocaoglu, Oktay Talaz, Huseyin Cavdar, Murat Senturk, Deniz Eki̇nci̇

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Glutathione reductase (GR) is a crucial antioxidant enzyme which is responsible for the maintenance of the antioxidant GSH (glutathione) molecule. Antimalarial effects of some chemical molecules are attributed to their inhibition of GR; thus inhibitors of this enzyme are expected to be promising candidates for the treatment of malaria. In this work, GR inhibitory properties of N-Methylpyrrole derivatives are reported. Firstly, GR was purified by means of affinity chromatography using 2’,5’-ADP-Sepharose 4B as ligand. Enzymatic activity was measured by Beutler’s method. Synthesis of the compounds was approved by thin layer chromatography and column chromatography. Different inhibitor concentrations were used and all compounds were tested in triplicate at each concentration used. It was found that all compounds have better inhibitory activity than the strong GR inhibitor N,N-bis(2-chloroethyl)-N-nitrosourea, especially three molecules, 8m, 8n, and 8q, are the best among them with low micromolar I₅₀ values. Findings of our study indicate that these Schiff base derivatives are strong GR inhibitors which can be used as leads for designation of novel antimalaria candidates.

Keywords: glutathione reductase, antimalaria, inhibitor, enzyme

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Authors: Mirza Popovac

Abstract:

This paper investigates the application of the vortex tubes towards increasing the efficiency of high temperature heat pumps based on natural refrigerants, by recovering a part of the expansion work within the refrigerant cycle. To this purpose the 3D Navier-Stokes solver is used to perform a set of numerical simulations, investigating the vortex tube performance. Firstly, the fluid flow and heat transfer characteristics are analyzed for standard configurations of vortex tubes, and the obtained results are validated against the experimental and numerical data available in literature. Subsequently, different geometry specifications are analyzed, as well as the interplay between relevant heat pump operating conditions and the properties of natural refrigerants. Finally, the characteristic curve of performance will be derived for investigated vortex tubes specifications when used within high temperature heat pumps.

Keywords: heat pump, vortex tube, CFD, natural refrigerant

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Authors: Michael Dole, Pierre Ninin, Denis Raffourt

Abstract:

Most of the CERN’s facilities hosting particle accelerators are large, underground and radioactive areas. All fire detection systems installed in such areas, shall be carefully studied to cope with the particularities of this stringent environment. The detection equipment usually chosen by CERN to secure these underground facilities are based on air sampling technology. The electronic equipment is located in non-radioactive areas whereas air sampling networks are deployed in radioactive areas where fire detection is required. The air sampling technology provides very good detection performances and prevent the "radiation-to-electronic" effects. In addition, it reduces the exposure to radiations of maintenance workers and is permanently available during accelerator operation. In order to protect the Super Proton Synchrotron and its 7 km tunnels, a specific long distance aspirating smoke detector has been developed to detect smoke at up to 700 meters between electronic equipment and the last air sampling hole. This paper describes the architecture, performances and return of experience of the long distance fire detection system developed and installed to secure the CERN Super Proton Synchrotron tunnels.

Keywords: air sampling, fire detection, long distance, radioactive areas

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Authors: J. M. Counsell, Y. Khalid, M. J. Stewart

Abstract:

Achieving nearly zero carbon heating continues to be identified by UK government analysis as an important feature of any lowest cost pathway to reducing greenhouse gas emissions. Heat currently accounts for 48% of UK energy consumption and approximately one third of UK’s greenhouse gas emissions. Heat Networks are being promoted by UK investment policies as one means of supporting hybrid heat pump based solutions. To this effect the RISE (Renewable Integrated and Sustainable Electric) heating system project is investigating how an all-electric heating sourceshybrid configuration could play a key role in long-term decarbonisation of heat.  For the purposes of this study, hybrid systems are defined as systems combining the technologies of an electric driven air source heat pump, electric powered thermal storage, a thermal vessel and micro-heat network as an integrated system.  This hybrid strategy allows for the system to store up energy during periods of low electricity demand from the national grid, turning it into a dynamic supply of low cost heat which is utilized only when required. Currently a prototype of such a system is being tested in a modern house integrated with advanced controls and sensors. This paper presents the virtual performance analysis of the system and its design for a micro heat network with multiple dwelling units. The results show that the RISE system is controllable and can reduce carbon emissions whilst being competitive in running costs with a conventional gas boiler heating system.

Keywords: gas boilers, heat pumps, hybrid heating and thermal storage, renewable integrated and sustainable electric

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Authors: Nicolas Giraudo, Peter Thissen

Abstract:

In this paper we bring up new aspects of the metal proton exchange reaction (MPER, also called early stage hydration): (1) its dependence of the number of protons consumed by the preferential exchanged cations on the pH value applied at the water/wollastonite interface and (2) strong anisotropic characteristics detected in atomic force microscopy (AFM) and low energy ion scattering spectroscopy measurements (LEIS). First we apply density functional theory (DFT) calculations to compare the kinetics of the reaction on different wollastonite surfaces, and combine it with ab initio thermodynamics to set up a model describing (1) the release of Ca in exchange with H coming from the water/wollastonite interface, (2) the dependence of the MPER on the chemical potential of protons. In the second part of the paper we carried out in-situ AFM and inductive coupled plasma atomic emission spectroscopy (ICP-OES) measurements in order to evaluate the predicted values. While a good agreement is found in the basic and neutral regime (pH values from 14-4), an increasing mismatch appears in the acidic regime (pH value lower 4). This is finally explained by non-equilibrium etching, dominating over the MPER in the very acidic regime.

Keywords: anisotropy, calcium silicate, cement, density functional theory, hydration

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Authors: Hadjer Didouh, Izzaddine Sameut Bouhaik, Mohammed Hadj Meliani

Abstract:

This research delves into the intricate dynamics of biofilm adhesion on surfaces, particularly focusing on the widely employed X52 surface in oil and gas industry pipelines. Biofilms, characterized by microorganisms within a self-produced matrix, pose significant challenges due to their detrimental impact on surfaces. Our study integrates advanced molecular techniques and cutting-edge microscopy, such as scanning electron microscopy (SEM), to identify microbial communities and visually assess biofilm adhesion. Simultaneously, we concentrate on the X52 surface, utilizing impedance spectroscopy and potentiodynamic polarization to gather electrochemical responses under various conditions. In conjunction with the broader investigation, we propose a novel approach to mitigate biofilm-induced corrosion challenges. This involves environmentally friendly inhibitors derived from plants, offering a sustainable alternative to conventional chemical treatments. Our inquiry screens and selects inhibitors based on their efficacy in hindering biofilm formation and reducing corrosion rates on the X52 surface. This study contributes valuable insights into the interplay between electrochemical processes and biofilm attachment on the X52 surface. Furthermore, the outcomes of this research have broader implications for the oil and gas industry, where biofilm-related corrosion is a persistent concern. The exploration of eco-friendly inhibitors not only holds promise for corrosion control but also aligns with environmental considerations and sustainability goals. The comprehensive nature of this research aims to enhance our understanding of biofilm dynamics, provide effective strategies for corrosion mitigation, and contribute to sustainable practices in pipeline management within the oil and gas sector.

Keywords: bio-corrosion, biofilm, attachment, X52, metal/bacteria interface

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Authors: Mohanapriya Subramanian, V. Raj

Abstract:

Direct methanol fuel cells (DMFCs) are considered to be one of the most promising candidates for portable and stationary applications in the view of their advantages such as high energy density, easy manipulation, high efficiency and they operate with liquid fuel which could be used without requiring any fuel-processing units. Electrolyte membrane of DMFC plays a key role as a proton conductor as well as a separator between electrodes. Increasing concern over environmental protection, biopolymers gain tremendous interest owing to their eco-friendly bio-degradable nature. Pectin is a natural anionic polysaccharide which plays an essential part in regulating mechanical behavior of plant cell wall and it is extracted from outer cells of most of the plants. The aim of this study is to develop and demonstrate pectin based polymer composite membranes as methanol impermeable polymer electrolyte membranes for DMFCs. Pectin based nanocomposites membranes are prepared by solution-casting technique wherein pectin is blended with chitosan followed by the addition of optimal amount of sulphonic acid modified Titanium dioxide nanoparticle (S-TiO2). Nanocomposite membranes are characterized by Fourier Transform-Infra Red spectroscopy, Scanning electron microscopy, and Energy dispersive spectroscopy analyses. Proton conductivity and methanol permeability are determined into order to evaluate their suitability for DMFC application. Pectin-chitosan blends endow with a flexible polymeric network which is appropriate to disperse rigid S-TiO2 nanoparticles. Resulting nanocomposite membranes possess adequate thermo-mechanical stabilities as well as high charge-density per unit volume. Pectin-chitosan natural polymeric nanocomposite comprising optimal S-TiO2 exhibits good electrochemical selectivity and therefore desirable for DMFC application.

Keywords: biopolymers, fuel cells, nanocomposite, methanol crossover

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Authors: Jean Paul M. Milambo

Abstract:

Purpose: Aromatase inhibitors (AIs) are indicated in the treatment of hormone-receptive breast cancer in postmenopausal women in various settings. Studies have shown cardiovascular events in some developed countries. To date the data is sparce for evidence-based recommendations in African clinical settings due to lack of cancer registries, capacity building and surveillance systems. Therefore, this study was conducted to assess the feasibility of HyBeacon® probe genotyping adjunctive to standard care for timely prediction and diagnosis of Aromatase inhibitors (AIs) associated adverse events in breast cancer survivors in Africa. Methods: Cross sectional study was conducted to assess the knowledge of POCT among six African countries using online survey and telephonically contacted. Incremental cost effectiveness ratio (ICER) was calculated, using diagnostic accuracy study. This was based on mathematical modeling. Results: One hundred twenty-six participants were considered for analysis (mean age = 61 years; SD = 7.11 years; 95%CI: 60-62 years). Comparison of genotyping from HyBeacon® probe technology to Sanger sequencing showed that sensitivity was reported at 99% (95% CI: 94.55% to 99.97%), specificity at 89.44% (95% CI: 87.25 to 91.38%), PPV at 51% (95%: 43.77 to 58.26%), and NPV at 99.88% (95% CI: 99.31 to 100.00%). Based on the mathematical model, the assumptions revealed that ICER was R7 044.55. Conclusion: POCT using HyBeacon® probe genotyping for AI-associated adverse events maybe cost effective in many African clinical settings. Integration of preventive measures for early detection and prevention guided by different subtype of breast cancer diagnosis with specific clinical, biomedical and genetic screenings may improve cancer survivorship. Feasibility of POCT was demonstrated but the implementation could be achieved by improving the integration of POCT within primary health cares, referral cancer hospitals with capacity building activities at different level of health systems. This finding is pertinent for a future envisioned implementation and global scale-up of POCT-based initiative as part of risk communication strategies with clear management pathways.

Keywords: breast cancer, diagnosis, point of care, South Africa, aromatase inhibitors

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