Search results for: magnetoelastically induced perpendicular magnetic anisotropy

Authors: Ross Calvert, Colin Whittaker, Alison Raby, Alistair G. L. Borthwick, Ton S. van den Bremer

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Large concentrations of plastic have polluted the seas in the last half century, with harmful effects on marine wildlife and potentially to human health. Plastic pollution will have lasting effects because it is expected to take hundreds or thousands of years for plastic to decay in the ocean. The question arises how waves transport plastic in the ocean. The predominant motion induced by waves creates ellipsoid orbits. However, these orbits do not close, resulting in a drift. This is defined as Stokes drift. If a particle is infinitesimally small and the same density as water, it will behave exactly as the water does, i.e., as a purely Lagrangian tracer. However, as the particle grows in size or changes density, it will behave differently. The particle will then have its own inertia, the fluid will exert drag on the particle, because there is relative velocity, and it will rise or sink depending on the density and whether it is on the free surface. Previously, plastic pollution has all been considered to be purely Lagrangian. However, the steepness of waves in the ocean is small, normally about α = k₀a = 0.1 (where k₀ is the wavenumber and a is the wave amplitude), this means that the mean drift flows are of the order of ten times smaller than the oscillatory velocities (Stokes drift is proportional to steepness squared, whilst the oscillatory velocities are proportional to the steepness). Thus, the particle motion must have the forces of the full motion, oscillatory and mean flow, as well as a dynamic buoyancy term to account for the free surface, to determine whether inertia is important. To track the motion of a floating inertial particle under wave action requires the fluid velocities, which form the forcing, and the full equations of motion of a particle to be solved. Starting with the equation of motion of a sphere in unsteady flow with viscous drag. Terms can added then be added to the equation of motion to better model floating plastic: a dynamic buoyancy to model a particle floating on the free surface, quadratic drag for larger particles and a slope sliding term. Using perturbation methods to order the equation of motion into sequentially solvable parts allows a parametric equation for the transport of inertial finite-sized floating particles to be derived. This parametric equation can then be validated using numerical simulations of the equation of motion and flume experiments. This paper presents a parametric equation for the transport of inertial floating finite-size particles by ocean waves. The equation shows an increase in Stokes drift for larger, less dense particles. The equation has been validated using numerical solutions of the equation of motion and laboratory flume experiments. The difference in the particle transport equation and a purely Lagrangian tracer is illustrated using worlds maps of the induced transport. This parametric transport equation would allow ocean-scale numerical models to include inertial effects of floating plastic when predicting or tracing the transport of pollutants.

Keywords: perturbation methods, plastic pollution transport, Stokes drift, wave flume experiments, wave-induced mean flow

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Authors: I. Georgousopoulou, S. Vouyiouka, C. Papaspyrides

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The hydrolytic degradation of poly(butylene succinate) (PBS) was investigated when exposed to different humidity-temperature environments. To this direction different PBS grades were submitted to hydrolysis runs. Results indicated that the increment of hydrolysis temperature and relative humidity induced significant decrease in the molecular weight and thermal properties of the bioplastic. Τhe derived data can be considered to construct degradation kinetics based on carboxyl content variation versus time.

Keywords: hydrolytic degradation, physical ageing, poly(butylene succinate), polyester

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Authors: Nura Lawal, Lawal Suleiman Bilbis, Rabiu Aliyu Umar, Anas A. Sabir

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Metabolic syndrome (MS) a high-risk condition involving obesity, dyslipidemia, hypertension, and diabetes mellitus is prevalent in Nigeria. The study aims to formulate an antioxidant-rich nutraceutical from locally available foodstuff (onion, garlic, ginger, tomato, lemon, palm oil, watermelon seeds) and investigate their effects on blood pressure, body weight, serum glucose, lipid profile, insulin and oxidative stress markers in salt-induced rats. The rats were placed on 8% salt diet for 6 weeks and then supplementation and treatment with nutraceutical and nifedipine in the presence of salt diet for additional 4 weeks. Feeding rats with salt diet for 6 weeks increased blood pressure and body weight of the salt-loaded rats relative to control. Significant (P < 0.001) increase in serum blood glucose and lipid profile, and the decrease in high-density lipoprotein-cholesterol (HDL-C) was observed in salt-loaded rats as compared with control. Both supplementation and treatment (nifedipine) lowered the blood pressure but the only supplementation lowered the body weight. Supplementation with nutraceutical resulted in significant (P < 0.001) decrease in the serum blood glucose, lipid profile, malonyldialdehyde (MDA), insulin levels, insulin resistance, and increased HDL-C and antioxidant indices. The percentage protection against atherogenesis was 76.5±2.13%. There is strong positive correlation between blood pressure, body weight and serum blood glucose, lipid profile, markers of oxidative stress and strong negative correlation with HDL-C and antioxidant status. The results suggest that the nutraceuticals are useful in reversing most of the component of metabolic syndrome and might be beneficial in the treatment of patients with metabolic syndrome.

Keywords: metabolic syndrome, hypertension, diabetes mallitus, obesity

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Authors: Alain Rousseau, Alfred Aragones, Gilles Rougier

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The study is based on lightning and surge standards mainly the EN series 62305 for facility protection, EN series 61643 for Low Voltage Surge Protective Devices, High Voltage surge arrester standard en 60099-4 and the traction arrester standards namely EN 50526-1 and 50526-1 dealing respectively with railway applications fixed installations D.C. surge arresters and voltage limiting devices. The more severe stress for tramways installations is caused by direct lightning on the catenary line. In such case, the surge current propagates towards the various poles and sparkover the insulators leading to a lower stress. If the impact point is near enough, a significant surge current will flow towards the traction surge arrester that is installed on the catenary at the location the substation is connected. Another surge arrester can be installed at the entrance of the substation or even inside the rectifier to avoid insulation damages. In addition, surge arresters can be installed between + and – to avoid damaging sensitive circuits. Based on disturbances encountered in a substation following a lighting event, the engineering department of RATP has decided to investigate the cause of such damage and more generally to question the efficiency of the various possible protection means. Based on the example of a recent tramway line the paper present the result of a lightning study based on direct lightning strikes. As a matter of fact, the induced surges on the catenary are much more frequent but much less damaging. First, a lightning risk assessment is performed for the substations that takes into account direct lightning and induced lightning both on the substation and its connected lines such as the catenary. Then the paper deals with efficiency of the various surge arresters is discussed based on field experience and calculations. The efficiency of the earthing system used at the bottom of the pole is also addressed based on high frequency earthing measurement. As a conclusion, the paper is making recommendations for an enhanced efficiency of existing protection means.

Keywords: surge arrester, traction, lightning, risk, surge protective device

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Authors: Wei-Wen Hu, Yong-Zhi Zhong

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Depositing conductive polypyrrole (PPy) onto elastic polydimethylsiloxane (PDMS) substrate can obtain a highly stretchable conductive film, which can be used to construct a bioreactor to cyclically stretch and electrically stimulate surface cells. However, how to completely harvest these stimulated muscle tissue to repair damaged muscle is a challenge. To address this concern, N-isopropylacrylamide (NIPAAm), a monomer of temperature-sensitive polymer, was added during the polymerization of pyrrole on PDMS so that the resulting P(Py-co-NIPAAm)/PDMS should own both conductivity and thermo-sensitivity. Therefore, cells after stimulation can be completely harvested as cell sheets by reducing temperature. Mouse skeletal myoblast, C2C12 cells, were applied to examine our hypothesis. In electrical stimulation, C2C12 cells on P(Py-co-NIPAAm)/PDMS demonstrated the best myo-differentiation under the electric field of 1 V/cm. Regarding cyclic stretching, the strain equal to or higher than 9% can highly align C2C12 perpendicular to the stretching direction. The Western blotting experiments demonstrated that the cell sheets harvested by cooling reserved more extracellular matrix (ECM) than cells collected by the traditional trypsin digestion method. Immunostaining of myosin heavy chain protein (MHC) indicated that both mechanical and electrical stimuli effectively increased the number of myotubes and the differentiation ratio, and the myotubes can be aligned by cyclic stretching. Stimulated cell sheets can be harvested by cooling, and the alignment of myotubes was still maintained. These results suggested that the deposition of P(Py-co-NIPAAm) on PDMS can be applied to harvest intact cell sheets after cyclic stretching and electrical stimulation, which increased the feasibility of bioreactor for the application of tissue engineering and regenerative medicine.

Keywords: bioreactor, cell sheet, conductive polymer, cyclic stretching, electrical stimulation, muscle tissue engineering, myogenesis, thermosensitive hydrophobicity

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Authors: Natalia V. Naryzhnaya, Alexandr V. Mukhomedzyanov, Ivan A. Derkachev, Boris K. Kurbatov, Leonid N. Maslov

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Background: Techniques of adaptation to hypoxia and remote postconditioning (RPost) have great prospects for use in the clinic. However, recent studies have shown low efficacy of remote postconditioning in patients with AMI. We hypothesize that the reasons for this inefficiency may be metabolic disorders, which are very common, especially in patients with cardiovascular disease, and age of patients. The purpose of the study was to reveal the effectiveness of adaptation to chronic hypoxia and RPost. To determine the possible relationship between the decrease in the effectiveness of projective impacts and disorders of carbohydrate and lipid metabolism. Design: The study was carried out on Wistar rats 60 day old. MetS was induced by high-carbohydrate, high-fat diet (HСHFD). Modeling MS led to the formation of obesity, hypertension, impaired lipid and carbohydrate metabolism, hyperleptinemia, and moderate stress. Groups with adaptation to chronic hypoxia were subjected to hypoxia for 21 days at 12% O2 and 0.3% CO2 after complete of HСHFD. All animals were subjected to 45 min coronary occlusion and 120 min reperfusion. Groups with RPost, immediately after the end of ischemia, tourniquets were applied to the hind limbs in the area of the hip joint (3 times in the mode of 5 min ischemia, 5 min reperfusion). Results: RPost led to a twofold reduction of infarct size in rats with intact metabolism (р < 0.0001), while in rats with MetS, a decrease in infarct size during RPost was 25 % (p = 0.00003). A direct correlation was found between of infarct size during RPost and the serum leptin level of rats with MetC (r = 0.85). The presented data suggested that a decrease in the efficiency of remote postconditioning in rats with diet-induced metabolic syndrome depends on serum leptin. Chronic hypoxia resulted in a 38% reduced in infarct size in metabolically intact rats. The decrease of cardioprotection was observed in rats with chronic hypoxia and MetS. Infarct size showed a direct correlation with impaired glucose tolerance (AUC, glucose tolerance test, r = 0.034) and serum triglyceride levels (r = 0.39). Our study showed the dependence of cardioprotection in rats with metabolic syndrome during chronic hypoxia and DPost on opioids in the blood serum and myocardium, protein kinase C and NO synthase activity. Conclusion: The results obtained showed that the infarct-limiting efficiency of adaptation to hypoxia and remote postconditioning is reduced or completely absent in animals with metabolic syndrome. The increase in the infarction, in this case, directly depends on the disturbances in carbohydrate. lipid metabolism and opioids signaling. Funding: Investigation of effectiveness of chronic hypoxia at the metabolic syndrome was carried out within the support of Russian Science Foundation Grant 22-15-00048. Studies of the mechanisms of arterial hypertension in induced metabolic syndrome were carried out within the framework of the state assignment (122020300042-4). The work was performed using the Center for Collective Use "Medical Genomics".

Keywords: chronic hypoxia, opioids, remote postconditioning, metabolic syndrome

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Authors: Kuan Yu Lin, Shih Chih Chen

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This study focuses on the Al/HfO₂/Si/Al structure to explore the electrical properties of the structure. This experiment uses a radio frequency magnetron sputtering system to deposit high dielectric materials on p-type silicon substrates of 1~10 Ω-cm (100). Consider the hafnium dioxide film as a dielectric layer. Post-deposition annealing at 750°C in nitrogen atmosphere. Electron beam evaporation of metallic aluminum is then used to complete the top/bottom electrodes. The metal is post-annealed at 450°C for 20 minutes in a nitrogen environment to complete the MOS component. Its dielectric constant, equivalent oxide layer thickness, oxide layer defects, and leakage current mechanism are discussed. At PDA 750°C-5s, the maximum k value was found to be 21.2, and the EOT was 3.68nm.

Keywords: high-k gate dielectrics, HfO₂, post deposition annealing, RF magnetic

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Authors: Eitan Yefenof

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Glucocorticoid (GC) hormones, e.g. Dexamethasone and Prednisone, are widely used in the therapy of leukemia and lymphoma owing to their apoptogenic effect on lymphoid cells. However, the emergence of GC resistant cells during therapy is a major cause for treatment failure, urging the need for novel strategies that maintain leukemia sensitivity to the pro-apoptotic activity of GCs. GCs act by binding to the GC receptor (GR), which, in its inactive state, is sequestered in the cytosol by a multi-subunit complex of heat shock proteins. Upon ligand binding, the complex dissociates, allowing GR activation and translocation to the nucleus, where it regulates transcription of multiple genes. We demonstrated that in addition to gene expression, GR also regulates microRNA (miR) expression. Deep-sequencing analysis revealed 14 miRs that are regulated in GC-sensitive but resistant leukemias upon treatment with GC. GC up-regulates miR-103, miR-15~16 and miR-30e/d, while down-regulates miR-17, mir-18a, miR-19a, miR-19b, miR-20a and miR-92a (members of the miR-17∼92a multi-cistron). Upon transfection, miR-103 confers GC apoptotic sensitivity to otherwise GC-resistant cell. Furthermore, knocking down miR-103 expression reduces the GC apoptotic response of sensitive cells. miR-103 abrogates c-Myc expression, an oncogenic transcription factor which is deregulated in many cancers. In addition, miR-103 up-regulates Bim, a pro-apoptotic protein crucial for GC-induced death. Activated glycogen synthase kinase 3 (GSK3) is also crucial for GC-induced apoptosis. GSK3 is active in GC-sensitive but not in GC-resistant cells. We found that GSK3 associates with the GR multi-subunit complex. Upon GC exposure, it dissociates from the GR and interacts with Bim to enable activation of the mitochondrial apoptosis pathway. miR-103 mediated c-Myc ablation is followed by down-regulation of the multi-cistron miR-17~92a, in particular miR-18a and miR-20a. miR-18a targets GR for degradation whereas miR-20a targets Bim degradation. Hence, miR-103 acts, in concert with Bim and GR, as a "tumor suppressor" that leads to reduced proliferation, cell-cycle arrest and cell death. We suggest that miR-103 can provide a diagnostic tool that predicts the sensitivity of leukemia to GC based therapy. Furthermore, exosomal delivery of miR-103 or up-regulation of the endogenous miR-103 could confer apoptotic sensitivity to resistant cells at the outset, thus becoming a useful therapeutic tool combined with GCs.

Keywords: apoptosis, leukemia, micro-RNA, steroids

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Authors: Mahendran Ganesan, Sanjeet Kumar Verma, Zafar Iqbal, Ashish Chandran, Zakir Husain, Shama Afroz, Sana Shahid, Laiq Ur Rahman

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Highly efficient in vitro regeneration system has been developed for Swertia chirayita (Roxb. ex Fleming) H. Karst, a high prized traditional medicinal plant to treat numerous ailments such as liver disorders, malaria and diabetes and are reported to have a wide spectrum of pharmacological properties. Its medicinal usage is well-documented in Indian pharmaceutical codex, the British and the American pharmacopeias, and in different traditional medicine such as the Ayurveda, Unani and Siddha medical systems. Nodal explants were cultured on MS medium supplemented with various phytohormones for multiple shoot induction. The nodal segments failed to respond in growth regulator free medium. All the concentrations of BAP, Kin and TDZ facilitated shoot bud break and multiple shoot induction. Among the various cytokinins tested, BAP was found to be more effective with respect to initiation and subsequent development of shoots. Of the various concentrations BAP tested, BAP at 4.0 mg/L showed the higher average number of shoot regeneration (10.80 shoots per explant). Kin at 4 mg/L and TDZ at 4 mg/L induced 5.70 and 04.5+0 shoots per explant, respectively. Further increase in concentration did not favour an increase in the number of shoots. However, these shoots failed to elongate further. Hence, addition of GA₃ (1 mg/L) was added to the above medium. This treatment resulted in the elongation of shoots (2.50 cm) and a further increase in the number of microshoots (34.20 shoots/explant). Roots were also induced in the same medium containing BAP (4 mg/L) + GA₃ (1 mg/L) + NAA (0.5 mg/L). In vitro derived plantlets with well-developed roots were transferred to the potting media containing garden soil: sand: vermicompost (2:1:1). Plantlets were covered with a polyethylene bag and irrigated with water. The pots were maintained at 25 ± 2ºC, and then the polyethylene cover was gradually loosened, thus dropping the humidity (65–70%). This procedure subsequently resulted in in vitro hardening of the plantlet.

Keywords: micropropagation, nodal explant, plant growth regulators, Swertia chirayita

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Authors: Artur Cichowicz

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The last active mine in the Central Rand Goldfields area (50 km x 15 km) ceased operations in 2008. This resulted in the closure of the pumping stations, which previously maintained the underground water level in the mining voids. As a direct consequence of the water being allowed to flood the mine voids, seismic activity has increased directly beneath the populated area of Johannesburg. Monitoring of seismicity in the area has been on-going for over five years using the network of 17 strong ground motion sensors. The objective of the project is to improve strategies for mine closure. The evolution of the seismicity pattern was investigated in detail. Special attention was given to seismic source parameters such as magnitude, scalar seismic moment and static stress drop. Most events are located within historical mine boundaries. The seismicity pattern shows a strong relationship between the presence of the mining void and high levels of seismicity; no seismicity migration patterns were observed outside the areas of old mining. Seven years after the pumping stopped, the evolution of the seismicity has indicated that the area is not yet in equilibrium. The level of seismicity in the area appears to not be decreasing over time since the number of strong events, with Mw magnitudes above 2, is still as high as it was when monitoring began over five years ago. The average rate of seismic deformation is 1.6x1013 Nm/year. Constant seismic deformation was not observed over the last 5 years. The deviation from the average is in the order of 6x10^13 Nm/year, which is a significant deviation. The variation of cumulative seismic moment indicates that a constant deformation rate model is not suitable. Over the most recent five year period, the total cumulative seismic moment released in the Central Rand Basin was 9.0x10^14 Nm. This is equivalent to one earthquake of magnitude 3.9. This is significantly less than what was experienced during the mining operation. Characterization of seismicity triggered by a rising water level in the area can be achieved through the estimation of source parameters. Static stress drop heavily influences ground motion amplitude, which plays an important role in risk assessments of potential seismic hazards in inhabited areas. The observed static stress drop in this study varied from 0.05 MPa to 10 MPa. It was found that large static stress drops could be associated with both small and large events. The temporal evolution of the inter-event time provides an understanding of the physical mechanisms of earthquake interaction. Changes in the characteristics of the inter-event time are produced when a stress change is applied to a group of faults in the region. Results from this study indicate that the fluid-induced source has a shorter inter-event time in comparison to a random distribution. This behaviour corresponds to a clustering of events, in which short recurrence times tend to be close to each other, forming clusters of events.

Keywords: inter-event time, fluid induced seismicity, mine closure, spectral parameters of seismic source

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Authors: Rajish Shil, Amal Alduhoori, Vipin Thomachan, Jamal Teir, Radhakrishnan Renganathan

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Background: Antiphospholipid antibody syndrome (APS) has a broad spectrum of thrombotic and non-thrombotic clinical manifestations. We present a case of APS presenting with seizure, stroke, and atrial mass. Case Description: A 38-year-old male presented with headache of 10 days duration and tonic-clonic seizure. The neurological examination was normal. Magnetic resonance imaging of brain showed small acute right cerebellar infarct. Magnetic resonance angiography of brain and neck showed a focal narrowing in the origin of the internal carotid artery bilaterally. Electroencephalogram was normal. He was started on aspirin, atorvastatin, and carbamazepine. Transthoracic and trans-esophageal echocardiography showed a pedunculated and lobular atrial mass, measuring 1 X 1.5 cm, which was freely mobile across mitral valve opening across the left ventricular inflow. Autoimmune screening showed positive Antiphospholipid antibodies in high titer (Cardiolipin IgG > 120 units/ml, B2 glycoprotein IgG 90 units/mL). Anti-nuclear antibody was negative. Erythrocyte sedimentation rate and C-reactive protein levels were normal. Platelet count was low (111 x 109/L). The patient underwent successful surgical removal of the mass, which looked like a thrombotic clot, and Histopathological analysis confirmed it as a fibrinous clot, with no evidence of tumor cells. The patient was started on full anticoagulation treatment and was followed up regularly in the clinic, where our patient did not have any further complications from the disease. Discussion: Our patient was diagnosed to have APS based on the features of high positive anticardiolipin antibody IgG and B2 glycoprotein IgG levels, Stroke, thrombocytopenia, and abnormal echo findings. Thrombotic vegetation can mimic an atrial myxoma on echo. Conclusion: APS can present with neurological and cardiac manifestations, and therefore a high index of suspicion is necessary for a diagnosis of the disease as it can affect both short and long term treatment plans and prognosis. Therefore, in patients presenting with neurological symptoms like seizures, weakness and radiological diagnosis of stroke in a young patient, where atrial masses could be thought to be the cause of stroke, they should be screened for any concomitant findings of thrombocytopenia and/or activated partial thromboplastin time prolongation, which should raise the suspicion of vasculitis, specifically APS to be the primary cause of the clinical presentation.

Keywords: antiphospholipid syndrome, seizures, atrial mass, stroke

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Authors: Richa Shri, Varinder Singh, Kundan Singh Bora, Abhishek Bhanot, Rahul Kumar, Amit Kumar, Ravinder Kaur

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The term ‘neuroprotection’ means preserving/salvaging function and structure of neurons. Neuroprotection is an adjunctive treatment option for neurodegenerative disorders. Oxidative stress is considered a major culprit in neurodegenerative disorders; hence, management strategies include use of antioxidants. Our search for a neuroprotective agent began with Allium cepa L. or onions, (family Amaryllidaceae) - a potent antioxidant. We have investigated the neuroprotective potential of onions in experimental models of ischemic stroke, diabetic neuropathy, neuropathic pain, and dementia. In pre and post-ischemic stroke model, the methanol extract of outer scales of onion bulbs (MEOS) prevented memory loss and motor in-coordination; reduced oxidative stress and cerebral infarct size. This also prevented and ameliorated diabetic neuropathy in mice. The MEOS was fractionated to yield a flavonoid rich fraction (FRF) that successfully reversed ischemia-reperfusion induced neuronal damage, thereby demonstrating that the flavonoids are responsible for the activity. The FRF effectively ameliorated chronic constriction induced neuropathic pain in rats. The FRF was subjected to bioactivity-guided fractionated. It was seen that FRF is more effective as compared to the isolated components probably due to synergism among the constituents (i.e., quercetin and quercetin glucosides) in the FRF. The outer scales of onion bulbs have great potential for prevention as well as for treatment of neuronal disorders. Red onions, with higher amounts of flavonoids as compared to the white onions, produced more significant neuroprotection. Thus, the standardized FRF from the waste material of a commonly used vegetable, especially the red variety, may be developed as a valuable neuroprotective agent.

Keywords: Allium cepa, antioxidant activity, flavonoid rich fraction, neuroprotection

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Authors: Gideon Baffoe, Hirotaka Matsuda

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Rural livelihood systems are known to be inherently vulnerable. Attempt to reduce vulnerability is linked to developing resilience to both internal and external shocks, thereby increasing the overall sustainability of livelihood systems. The shocks and stresses could be induced by natural processes such as the climate and/or by social dynamics such as institutional failure. In this wise, livelihood vulnerability is understood as a combined effect of biophysical, economic, and social processes. However, previous empirical studies on livelihood vulnerability in the context of rural areas across the globe have tended to focus more on climate-induced vulnerability assessment with few studies empirically partially considering the multiple dimensions of livelihood vulnerability. This has left a gap in our understanding of the subject. Using the Livelihood Vulnerability Index (LVI), this study aims to comprehensively assess the livelihood vulnerability level of rural households using Ehiamenkyene, a community in the forest zone of Eastern Ghana as a case study. Though the present study adopts the LVI approach, it differs from the original framework in two respects; (1) it introduces institutional influence into the framework and (2) it appreciates the gender differences in livelihood vulnerability. The study utilized empirical data collected from 110 households’ in the community. The overall study results show a high livelihood vulnerability situation in the community with male-headed households likely to be more vulnerable than their female counterparts. Out of the seven subcomponents assessed, only two (socio-demographic profile and livelihood strategies) recorded low vulnerability scores of less than 0.5 with the remaining five (health status, food security, water accessibility, institutional influence and natural disasters and climate variability) recording scores above 0.5, with institutional influence being the component with the highest impact score. The results suggest that to improve the livelihood conditions of the people; there is the need to prioritize issues related to the operations of both internal and external institutions, health status, food security, water and climate variability in the community.

Keywords: assessment, gender, livelihood, rural, vulnerability

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Authors: Yi Hu, Chun-Chi Lin, Shau-En Yeh, Shin Lee

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In this study, p–n heterojunctions with La0.5Sr0.5CoO3 (LSCO) and W-doped VO2 thin films were fabricated by the radio frequency (r.f.) magnetron sputtering technique and sol-gel process, respectively. The thickness of VO2 and LSCO thin films are about 40 nm and 400 nm, respectively. Good crystalline match between LSCO and VO2 films was observed from the SEM. The built-in voltages for the junction are about 1.1 V and 2.3 V for the sample in the metallic and insulating state, respectively. The sample can undergo the current induced MIT during applying field when the sample was heated at 40 and 50ºC. This is in agreement with the value obtained from the difference in the work functions of LSCO and VO2. The band structure of the heterojunction was proposed based on the results of analysis.

Keywords: hetrojection, Mott transition, switching , VO2

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Authors: Mathew Saxon A, Aneeh Rajan, Sajeev P

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Many fluid flow applications employ different types of orifices to control the flow rate or to reduce the pressure. Discharge coefficients generally vary from 0.6 to 0.95 depending on the type of the orifice. The tabulated value of discharge coefficients of various types of orifices available can be used in most common applications. The upstream and downstream flow condition of an orifice is hardly considered while choosing the discharge coefficient of an orifice. But literature shows that the discharge coefficient can be affected by the presence of cross flow. Cross flow is defined as the condition wherein; a fluid is injected nearly perpendicular to a flowing fluid. Most researchers have worked on water being injected into a cross-flow of water. The present work deals with water to gas systems in which water is injected in a normal direction into a flowing stream of gas. The test article used in the current work is called thermal regulator, which is used in a liquid rocket engine to reduce the temperature of hot gas tapped from the gas generator by injecting water into the hot gas so that a cooler gas can be supplied to the turbine. In a thermal regulator, water is injected through an orifice in a normal direction into the hot gas stream. But the injection orifice had been calibrated under backpressure by maintaining a stagnant gas medium at the downstream. The motivation of the present study aroused due to the observation of a lower Cd of the orifice in flight compared to the calibrated Cd. A systematic experimental investigation is carried out in this paper to study the effect of cross-flow on the discharge coefficient of an orifice in water to a gas system. The study reveals that there is an appreciable reduction in the discharge coefficient with cross flow compared to that without cross flow. It is found that the discharge coefficient greatly depends on the ratio of momentum of water injected to the momentum of the gas cross flow. The effective discharge coefficient of different orifices was normalized using the discharge coefficient without cross-flow and it is observed that normalized curves of effective discharge coefficient of different orifices with momentum ratio collapsing into a single curve. Further, an equation is formulated using the test data to predict the effective discharge coefficient with cross flow using the calibrated Cd value without cross flow.

Keywords: cross flow, discharge coefficient, orifice, momentum ratio

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Authors: Siddhant Sethi, Yasuharu Takashima, Shigetaka Nakamura, Kenzo Fujimoto

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Site-directed mutagenesis is a renowned technique to introduce specific mutations in the genome. To achieve site-directed mutagenesis, many chemical and enzymatic approaches have been reported in the past like disulphite induced genome editing, CRISPR-Cas9, TALEN etc. The chemical methods are invasive whereas the enzymatic approaches are time-consuming and expensive. Most of these techniques are unusable in the cellular application due to their toxicity and other limitations. Photo-chemical cytosine deamination, introduced in 2010, is one of the major technique for enzyme-free single-point mutation of cytosine to uracil in DNA and RNA, wherein, 3-cyanovinylcarbazole nucleoside (CNVK) containing oligodeoxyribonucleotide (ODN) having CNVK at -1 position to that of target cytosine is reversibly crosslinked to target DNA strand using 366 nm and then incubated at 90ºC to accommodate deamination. This technique is superior to enzymatic methods of site-directed mutagenesis but has a disadvantage that it requires the use of high temperature for the deamination step which restricts its applicability in the in vivo applications. This study has been focused on improving the technique by reducing the temperature required for deamination. Firstly, the photo-cross-linker, CNVK has been modified by replacing cyano group attached to vinyl group with methyl ester (OMeVK), amide (NH2VK), and carboxylic acid (OHVK) to observe the acceleration in the deamination of target cytosine cross-linked to vinylcarbazole derivative. Among the derivatives, OHVK has shown 2 times acceleration in deamination reaction as compared to CNVK, while the other two derivatives have shown deceleration towards deamination reaction. The trend of rate of deamination reaction follows the same order as that of hydrophilicity of the vinylcarbazole derivatives. OHVK being most hydrophilic has shown highest acceleration while OMeVK is least hydrophilic has proven to be least active for deamination. Secondly, in the related study, the counter-base of the target cytosine, guanine has been replaced by inosine, 2-aminopurine, nebularine, and 5-nitroindole having distinct hydrogen bonding patterns with target cytosine. Among the ODNs with these counter bases, ODN with inosine has shown 12 fold acceleration towards deamination of cytosine cross-linked to CNVK at physiological conditions as compared to guanosine. Whereas, when 2-aminopurine, nebularine, and 5-nitroindole were used, no deamination reaction took place. It can be concluded that inosine has potential to be used as the counter base of target cytosine for the CNVK mediated photo-cross-linking induced deamination of cytosine. The increase in rate of deamination reaction has been attributed to pattern and number of hydrogen bonding between the cytosine and counter base. One of the important factor is presence of hydrogen bond between exo-cyclic amino group of cytosine and the counter base. These results will be useful for development of more efficient technique for site-directed mutagenesis for C → U transformations in the DNA/RNA which might be used in the living system for treatment of various genetic disorders and genome engineering for making designer and non-native proteins.

Keywords: C to U transformation, DNA editing, genome engineering, ultra-fast photo-cross-linking

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Authors: Jihede Haj Messaoud, Hamdi Omar, Hela Fakhfakh Ben Jemia, Chokri Yaich

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The Upper Lutetian alternating marl–limestone succession of Reineche Member was deposited over a warm shallow carbonate platform that permits Nummulites proliferation. High-resolution studies of 30 meters thick Nummulites-bearing Reineche Member, cropping out in Central Tunisia (Jebel Siouf), have been undertaken, regarding pronounced cyclical sedimentary sequences, in order to investigate the periodicity of cycles and their related orbital-scale oceanic and climatic changes. The palaeoenvironmental and palaeoclimatic data are preserved in several proxies obtainable through high-resolution sampling and laboratories measurement and analysis as magnetic susceptibility (MS) and carbonates contents in conjunction with a wireline logging tools. The time series analysis of proxies permits to establish cyclicity orders present in the studied intervals which could be linked to the orbital cycles. MS records provide high-resolution proxies for relative sea level change in Late Lutetian strata. The spectral analysis of MS fluctuations confirmed the orbital forcing by the presence of the complete suite of orbital frequencies in the precession of 23 ka, the obliquity of 41 ka, and notably the two modes of eccentricity of 100 and 405 ka. Regarding the two periodic sedimentary cycles detected by wavelet analysis of proxy fluctuations which coincide with the long-term 405 ka eccentricity cycle, the Reineche Member spanned 0,8 Myr. Wireline logging tools as gamma ray and sonic were used as a proxies to decipher cyclicity and trends in sedimentation and contribute to identifying and correlate units. There are used to constraint the highest frequency cyclicity modulated by a long term wavelength cycling apparently controlled by clay content. Interpreted as a result of variations in carbonate productivity, it has been suggested that the marl-limestone couplets, represent the sedimentary response to the orbital forcing. The calculation of cycle durations through Reineche Member, is used as a geochronometer and permit the astronomical calibration of the geologic time scale. Furthermore, MS coupled with carbonate contents, and fossil occurrences provide strong evidence for combined detrital inputs and marine surface carbonate productivity cycles. These two synchronous processes were driven by the precession index and ‘fingerprinted’ in the basic marl–limestone couplets, modulated by orbital eccentricity.

Keywords: magnetic susceptibility, cyclostratigraphy, orbital forcing, spectral analysis, Lutetian

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Authors: Kamsiah Jaarin, Yusof Kamisah, Faizah Othman Nurul Akmal Muhammad, Zakiah Jubri, Qodriyah Mohd Saad, Srijit Das

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Forty (40) normotensive adult male Sprague-Dawley rats aged three months weighing 180-200 g were divided into 4 groups with 10 rats per group: (1) normotensive control; (2) hypertensive rats; (3) hypertensive rats treated with Nigella sativa (2.5 ml/kg/day); and (4) hypertensive rats treated with nicardipine (5 mg/kg/day). After acclimatization, the hypertensive rats of the group 2, 3 and 4 were induced to be hypertensive by giving NW–nitro-L-arginine methyl ester (L-NAME; 30 mg/kg/day) in their drinking water for consecutive 7 days. After one week, rats in the group 3 were given a daily oral dose of 2.5 ml/kg/day of Nigella sativa (NS) by oral gavage. Rats in the group 4 were given nicardipine (5 mg/kg/day) via oral gavages. All rats in this study received L-NAME continuously throughout the treatment duration. The blood pressure will be measured pre-treatment and weekly for 8 weeks using power lab. Blood was taken before and at the end of study for measurement of nitric oxide. At the end of 8 weeks, the rats are sacrificed and descending thoracic aorta was disserted for measurement of vascular reactivity, and intracellular adhesion molecules (ICAM-1) and vascular cell adhesion molecules (VCAM-1). Nigella sativa reduced both systolic and diastolic BP compared to control and L-name group. The BP lowering effect of NS was comparable to nicardipine a calcium antagonist. The blood pressure lowering effect of NS was accompanied with an increasing relaxation response to nitroprusside and acetylcholine and reducing vasoconstriction response to epinephrine. L-NAME and nicardipine on the other hand, reduced plasma nitric oxide concentration. In contrast, NS increased NO concentration. However, Nigella sativa had no significant effect on aortic VCAM- 1 and ICAM-1 expression. In conclusion; Nigella sativa oil reduces both systolic and diastolic blood pressure in L-NAME treated rats. The antihypertensive effect of NS was comparable to nicardipine. The BP lowering effect may be mediated via stimulating nitric oxide release from vascular endothelium.

Keywords: Nigella sativa, ICAM, VCAM, blood pressure, vascular reactivity

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Authors: Omolola R. Ayepola, Nicole L. Brooks, Oluwafemi O. Oguntibeju

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The liver plays an important role in the regulation of blood glucose and is a target organ of hyperglycaemia. Hyperglycemia plays a crucial role in the onset of various liver diseases and may culminate into hepatopathy if untreated. Alteration in antioxidant defense and increase in oxidative stress that results in tissue injury is characteristic of diabetes. We evaluated the protective effects of kolaviron-a biflavonoid complex, on hepatic antioxidants, lipid peroxidation and apoptosis in the liver of diabetic rats. To induce type I diabetes, rats were injected with streptozotocin intraperitoneally at a single dose of 50 mg/kg. Oral treatment of diabetic rats with kolaviron (100 mg/kg) started on the 6th day after diabetes induction and continued for 6 weeks (5 times weekly). Diabetic rats exhibited a significant increase in the peroxidation of hepatic lipids as observed from the elevated level of malondialdehyde (MDA) estimated by High-Performance Liquid Chromatography. In addition, Oxygen Radical Absorbance Capacity (ORAC), ratio of reduced to oxidized glutathione (GSH/GSSG) and catalase (CAT) activity was decreased in the liver of diabetic rats. TUNEL assay revealed increased apoptotic cell death in the liver of diabetic rats. Examination of Pancreatic beta-cells by immunohistochemical methods revealed beta cell degeneration and reduction in beta cell/ islet area in the diabetic controls. Kolaviron-treatment increased the area of insulin immunoreactive beta-cells significantly. Kolaviron attenuated lipid peroxidation and apoptosis in the liver of diabetic rats, increased CAT activity GSH levels and the resultant GSH: GSSG. The ORAC of kolaviron-treated diabetic liver was restored to near-normal values. Kolaviron protects the liver against oxidative and apoptotic damage induced by hyperglycemia. The antidiabetic effect of kolaviron may also be related to its beneficial effects on beta-cell function.

Keywords: diabetes mellitus, kolaviron, oxidative stress, liver, apoptosis

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Authors: Dong Zhao

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Even though the recent claim of room temperature superconductivity by LK-99 was confirmed an unsuccessful attempt, this work reawakened people’s century striving to get applicable superconductors with Tc of room temperature or higher and under ambient pressure. One of the efforts was focusing on exploring the thorium salts. This is because certain thorium compounds revealed an unusual property of having both high electrical conductivity and diamagnetism or the so-called “coexistence of high electrical conductivity and diamagnetism.” It is well known that this property of the coexistence of high electrical conductivity and diamagnetism is held by superconductors because of the electron pairings. Consequently, the likelihood for these thorium compounds to have superconducting properties becomes great. However, as a surprise, these thorium salts possess this property at room temperature and atmosphere pressure. This gives rise to solid evidence for these thorium compounds to be room-temperature superconductors without a need for external pressure. Among these thorium compound superconductors claimed in that work, thorium di-iodide (ThI₂) is a unique one and has received comprehensive discussion. ThI₂ was synthesized and structurally analyzed by the single crystal diffraction method in the 1960s. Its special property of coexistence of high electrical conductivity and diamagnetism was revealed. Because of this unique property, a special molecular configuration was sketched. Except for an ordinary oxidation of +2 for the thorium cation, the thorium’s oxidation state in ThI₂ is +4. According to the experimental results, ThI₂‘s actual molecular configuration was determined as an unusual one of [Th4+(e-)2](I-)2. This means that the ThI₂ salt’s cation is composed of a [Th4+(e-)2]2+ cation core. In other words, the cation of ThI₂ is constructed by combining an oxidation state +4 of the thorium atom and a pair of electrons or an electron lone pair located on the thorium atom. This combination of the thorium atom and the electron lone pair leads to an oxidation state +2 for the [Th4+(e-)2]2+ cation core. This special construction of the thorium cation is very distinctive, which is believed to be the factor that grants ThI₂ the room temperature superconductivity. Actually, the key for ThI₂ to become a room-temperature superconductor is this characteristic electron lone pair residing on the thorium atom along with the formation of a network constructed by the thorium atoms. This network specializes in a way that allows the electron lone pairs to hop over it and, thus, to generate the supercurrent. This work will discuss, in detail, the special electrical and magnetic properties of ThI₂ as well as its structural features at ambient conditions. The exploration of how the electron pairing in combination with the structurally specialized network works together to bring ThI₂ into a superconducting state. From the experimental results, strong evidence has definitely pointed out that the ThI₂ should be a superconductor, at least at room temperature and under atmosphere pressure.

Keywords: co-existence of high electrical conductivity and diamagnetism, electron lone pair, room temperature superconductor, special molecular configuration of thorium di-iodide ThI₂

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Authors: Pintusorn Hansakul, Ruchilak Rattarom, Arunporn Itharat

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Background: Benjakul, a Thai traditional herbal formulation, comprises of five plants: Piper chaba, Piper sarmentosum, Piper interruptum, Plumbago indica, and Zingiber officinale. It has been widely used to treat cancer patients in the context of folk medicine in Thailand. This study aimed to investigate the cytotoxic effect of the ethanol extract of Benjakul against three non-small cell lung cancer (NSCLC) cell lines (NCI-H226, A549, COR-L23), small cell lung cancer (SCLC) cell line NCI-H1688 and normal lung fibroblast cell line MRC-5. The study further examined the molecular mechanisms underlying its cytotoxicity via induction of apoptosis in NCI-H226 cells. Methods: The cytotoxic effect of Benjakul was determined by SRB assay. The effect of Benjakul on cell cycle distribution was assessed by flow cytometric analysis. The apoptotic effects of Benjakul were determined by sub-G1 quantitation and Annexin V-FITC/PI flow cytometric analyses as well as by changes in caspase-3 activity. Results: Benjakul exerted potent cytotoxicity on NCI-H226 and A549 cells but lower cytotoxicity on COR-L23 and NCI-H1688 cells without any cytotoxic effect on normal cells. Molecular studies showed that Benjakul extract induced G2/M phase arrest in human NCI-H226 cells in a dose-dependent manner. The highest concentration of Benjakul (150 μg/ml) led to the highest increase in the G2/M population at 12 h, followed by the highest increase in the sub-G1 population (apoptotic cells) at 60 h. Benjakul extract also induced early apoptosis (AnnexinV +/PI−) in NCI-H226 cells in a dose- and time- dependent manner. Moreover, treatment with 150 μg/ml Benjakul extract for 36 h markedly increased caspase-3 activity by 3.5-fold, and pretreatment with the general caspase inhibitor z-VAD-fmk completely abolished such activity. Conclusions: This study reveals for the first time the regulation of apoptosis in human lung cancer NCI-H226 cells through caspase-dependent mechanism by Benjakul extract.

Keywords: apoptosis, Benjakul, caspase activation, cytotoxicity

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Authors: R. Sumalatha, M. V. Subramanyam

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In medical image processing the quality of the image is degraded in the presence of noise. Especially in ultra sound imaging and Magnetic resonance imaging the data was corrupted by signal dependent noise known as salt and pepper noise. Removal of noise from the medical images is a critical issue for researchers. In this paper, a new type of technique Adaptive Spatial Mask Filter (ASMF) has been proposed. The proposed filter is used to increase the quality of MRI and ultra sound images. Experimental results show that the proposed filter outperforms the implementation of mean, median, adaptive median filters in terms of MSE and PSNR.

Keywords: salt and pepper noise, ASMF, PSNR, MSE

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Authors: Chakrapani Pullagummi, Arun Jyothi Bheemagani, B. Chandra Sekhar Singh, Prem Kumar, A. Roja Rani

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Diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion and its action. The objective of present study was alloxan induced diabetes in S.D (Sprague Dawley) rats, treated with leaf extract of Andrographis paniculata and bark extract of Erythrina indica. Plant extract treated rats were analyzed biochemically and molecularly. on normal and diabetic rats. The changes in MDA (lipid peroxidation) and glucose (by GOD method) levels in blood of both normal and diabetic rat were analyzed. Diabetes induced rats were treated with methanolic extracts of Andrographis paniculata leaf and Erythrina indica bark which are of medicinal importance. Later after inducing diabetes the rats were treated with medicinal plant extracts, Andrographis paniculata leaf and Erythrina indica bark which are well known for their anti diabetic and antioxidative property in order to control the glucose and MDA levels. The blood plasma of diabetic and normal rats was analyzed for the levels of MDA (lipid peroxidation) and glucose levels. Results of this study suggested that the Andrographis paniculata leaf and Erythrina indica can be used as a potential natural antidiabetic agent for treating and postponing the appearance of complications that arise due to Diabetes. Molecular study deals with the analysis of binding mechanism of 2 selected natural compounds from Andrographis and Erythrina extracts against the novel target for type T2D namely PPAR-γ compared with Rosiglitazone (standard compound). The results revealed that most of the selected herbal lead compounds were effective targets against the receptors. These compounds showed favorable interactions with the amino acid residues thereby substantiating their proven efficacy as anti-diabetic compounds.

Keywords: andrographis paniculata, erythrina indica, alloxan, lipid peroxidation, blood glucose level, PPAR-γ

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Authors: Madhu Sarwan, Ritu Dubey, Sadhna Singh

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We have investigated the structural phase transition from Zinc-Blende (ZB) to Rock-Salt (RS) structure of TlxGa1-xAs by using Interaction Potential Model (IPM). The IPM consists of Coulomb interaction, Three-Body Interaction (TBI), Van Der Wall (vdW) interaction and overlap repulsive short range interaction. The structural phase transition has been computed by using the vegard’s law. The volume collapse is also computed for this alloy. We have also investigated the second order elastic constants with composition for the alloy TlxGa1-xAs.

Keywords: III-V alloy, elastic moduli, phase transition, semiconductors

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Authors: Mostafa Rajabi, Kazem Mahanpoor

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Performances of the methyl red (MR) dye adsorption on poly(methyl methacrylate)/graphene oxide (PMMA/GO) and poly(methyl methacrylate)/graphene oxide-Fe3O4 (PMMA/GO-Fe3O4) nanocomposites as adsorbents were investigated. Our results showed that for adsorption of MR dye on PMMA/GO-Fe3O4 and PMMA/GO nanocomposites, 80 minutes, 298 K, and pH 2 were the best contact time, temperature and pH value for process, respectively, because the optimum adsorption of the MR dye with both nanocomposite adsorbents were observed in these values of the parameters. The equilibrium study results showed that PMMA/GO-Fe3O4 and PMMA/GO were suitable adsorbents for MR dye removing and were best in agreement with the Langmuir isotherm model.

Keywords: adsorption, isotherm, methyl methacrylate, methyl red, nanocomposite, nano magnetic Fe3O4

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Authors: Surbhi Surbhi, Andrea Erni, Gunter Meister, Harold Cremer, Christophe Beclin

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MicroRNAs (miRNAs) are short 20-23 nucleotide long non-coding RNAs; there are 2605 miRNA in humans and 1936 miRNA in mouse in total (miRBase). The nervous system expresses the most abundant miRNA and most diverse. MiRNAs play a role in many steps during neurogenesis, like cell proliferation, differentiation, neural patterning, axon pathfinding, etc. Moreover, in vitro studies suggested a role in the regulation of local translation at the synapse, thus controlling neuronal plasticity. However, due to the specific structure of miRNA molecules, an in-vivo confirmation of the general role of miRNAs in the control of neuronal plasticity is still pending. For example, their small size and their high level of sequence homology make difficult the analysis of their cellular and sub-cellular localization in-vivo by in-situ hybridization. Moreover, it was found that only 40% of the expressed miRNA molecules in a cell are included in RNA-Induced Silencing Complexes (RISC) and, therefore, involved in inhibitory interactions while the rest is silent. Definitively, the development of new tools is needed to have a better understanding of the cellular function of miRNAs, in particular their role in neuronal plasticity. Here we describe a new technique called in-vivo AGO-APP designed to investigate miRNA expression and function in-vivo. This technique is based on the expression of a small peptide derived from the human RISC-complex protein TNRC6B, called T6B, which binds all known Argonaute (Ago) proteins with high affinity allowing the efficient immunoprecipitation of AGO-bound miRNAs. We have generated two transgenic mouse lines conditionally expressing T6B either ubiquitously in the cell or targeted at the synapse. A comparison of the repertoire of miRNAs immuno-precipitated from mature neurons of both mouse lines will provide us with a list of miRNAs showing a specific activity at the synapse. The physiological role of these miRNAs will be subsequently addressed through gain and loss of function experiments.

Keywords: RNA-induced silencing complexes, TNRC6B, miRNA, argonaute, synapse, neuronal plasticity, neurogenesis

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Authors: Katarzyna Palus, Jarosław Całka

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Gastrointestinal disorders, especially acid-related diseases, including peptic and duodenal ulcers, gastroesophageal reflux disease, upper GI bleeding or stress-related mucosal disease, are currently serious health issues encountered very frequently in patients worldwide. However, to date, the response of sympathetic neurons to gastric mucosal injury and local inflammation following hyperacidity is unknown. Thus, the present study was designed to determine possible changes in expression of galanin (GAL) in the CSMG neurons supplying the prepyloric area of the porcine stomach in a physiological state and following experimentally-induced hyperacidity by using combined retrograde tracing and double-labelling immunohistochemistry. The choice of the domestic pig as an experimental model in the present study is not accidental and is justified by the high degree of physiological and anatomical similarity to human digestive system functions. In this experiment ten juvenile female pigs of the Large White Polish breed were used. The animals were divided into two groups: control and animals with hydrochloric acid infusion (HCl). The neuronal retrograde marker Fast Blue (FB) was injected into the anterior prepyloric wall of the stomach of all animals. After 23 days, animals of the HCl-group were reintroduced into a state of general anesthesia and intragastrically given 5 ml/kg of body weight of 0.25 M aqueous solution of hydrochloric acid. On the 28th day, all animals were euthanized. The CSMG complexes were then collected and the CSMG cryostat sections were stained immunocytochemically for GAL and TH (tyrosine hydroxylase). Immunohistochemistry revealed that in the control group 8.40 ± 0.53 % out of 200 FB-positive CSMG neurons contained GAL. In HCl group upregulation of the GAL-IR neurons to 22.52 ± 1.18 % were observed. All GAL-IR neurons in both groups showed the simultaneously TH immunoreactivity. Increase in the expression of GAL in FB-positive neurons of the HCL group may suggest its participation in the protective mechanisms of neurons in different pathological processes, such as gastric hyperacidity.

Keywords: coeliac-superior mesenteric ganglion complex, gastric innervation, hyperacidity, immunohistochemistry

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Authors: Morgane Chatard, Clémentine Puech, Nathalie Perek, Frédéric Roche

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Several neurological disorders are linked to repeated hypoxia. The impact of such repeated hypoxic stress, on endothelial cells function of the blood-brain barrier (BBB) is little studied in the literature. Indeed, the study of hypoxic stress in cellular pathways is complex using hypoxia exposure because HIF 1α (factor induced by hypoxia) has a short half life. Our study presents an innovative induction method of repeated hypoxic stress, more reproducible, which allows us to study its impacts on an in vitro contact co-culture BBB model. Repeated hypoxic stress was induced by hydralazine (a mimetic agent of hypoxia pathway) during two hours and repeated during 24 hours. Then, BBB integrity was assessed by permeability measurements (transendothelial electrical resistance and membrane permeability), tight junction protein expressions (cell-ELISA and confocal microscopy) and by studying expression and activity of efflux transporters. First, this study showed that repeated hypoxic stress leads to a BBB’s dysfunction illustrated by a significant increase in permeability. This loss of membrane integrity was linked to a significant decrease of tight junctions’ protein expressions, facilitating a possible transfer of potential cytotoxic compounds in the brain. Secondly, we demonstrated that brain microvascular endothelial cells had set-up defence mechanism. These endothelial cells significantly increased the activity of their efflux transporters which was associated with a significant increase in their expression. In conclusion, repeated hypoxic stress lead to a loss of BBB integrity with a decrease of tight junction proteins. In contrast, endothelial cells increased the expression of their efflux transporters to fight against cytotoxic compounds brain crossing. Unfortunately, enhanced efflux activity could also lead to reducing pharmacological drugs delivering to the brain in such hypoxic conditions.

Keywords: BBB model, efflux transporters, repeated hypoxic stress, tigh junction proteins

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Authors: Anna Höfer, Johannes Herrmann, Patrick Meybohm, Christopher Lotz

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Mitochondria are pivotal for energy supply and regulation of cellular functions. Deficiencies of mitochondrial metabolism have been implicated in diverse stressful conditions including infections. Platelets are key mediators for thrombo-inflammation during development and resolution of acute respiratory distress syndrome (ARDS). Previous data point to an exhausted platelet phenotype in critically-ill patients with coronavirus 19 disease (COVID-19) impacting the course of disease. The objective of this work was to characterize platelet mitochondrial metabolism in patients suffering from COVID-19 ARDSA longitudinal analysis of platelet mitochondrial metabolism in 24 patients with COVID-19 induced ARDS compared to 35 healthy controls (ctrl) was performed. Blood samples were analyzed at two time points (t1=day 1; t2=day 5-7 after study inclusion). The activity of mitochondrial citrate synthase was photometrically measured. The impact of oxidative stress on mitochondrial permeability was assessed by a photometric calcium-induced swelling assay and the activity of superoxide dismutase (SOD) by a SOD assay kit. The amount of protein carbonylation and the activity of mitochondria complexes I-IV were photometrically determined. Levels of interleukins (IL)-1α, IL-1β and tumor necrosis factor (TNF-) α were measured by a Multiplex assay kit. Median age was 54 years, 63 % were male and BMI was 29.8 kg/m2. SOFA (12; IQR: 10-15) and APACHE II (27; IQR: 24-30) indicated critical illness. Median Murray Score was 3.4 (IQR: 2.8-3.4), 21/24 (88%) required mechanical ventilation and V-V ECMO support in 14/24 (58%). Platelet counts in ARDS did not change during ICU stay (t1: 212 vs. t2: 209 x109/L). However, mean platelet volume (MPV) significantly increased (t1: 10.6 vs. t2: 11.9 fL; p<0.0001). Citrate synthase activity showed no significant differences between ctrl and ARDS patients. Calcium induced swelling was more pronounced in patients at t1 compared to t2 and to ctrl (50µM; t1: 0.006 vs. ctrl: 0.016 ΔOD; p=0.001). The amount of protein carbonylation as marker for irreversible proteomic modification constantly increased during ICU stay and compared to ctrl., without reaching significance. In parallel, superoxid dismutase activity gradually declined during ICU treatment vs. ctrl (t2: - 29 vs. ctrl.: - 17 %; p=0.0464). Complex I analysis revealed significantly stronger activity in ARDS vs. ctrl. (t1: 0.633 vs. ctrl.: 0.415 ΔOD; p=0.0086). There were no significant differences in complex II, III or IV activity in platelets from ARDS patients compared to ctrl. IL-18 constantly increased during the observation period without reaching significance. IL-1α and TNF-α did not differ from ctrl. However, IL-1β levels were significantly elevated in ARDS (t1: 16.8; t2: 16.6 vs. ctrl.: 12.4 pg/mL; p1=0.0335, p2=0.0032). This study reveals new insights in platelet mitochondrial metabolism during COVID-19 caused ARDS. it data point towards enhanced platelet activity with a pronounced turnover rate. We found increased activity of mitochondria complex I and evidence for enhanced oxidative stress. In parallel, protective mechanisms against oxidative stress were narrowed with elevated levels of IL-1β likely causing a pro-apoptotic environment. These mechanisms may contribute to platelet exhaustion in ARDS.

Keywords: acute respiratory distress syndrome (ARDS), coronavirus 19 disease (COVID-19), oxidative stress, platelet mitochondrial metabolism

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Authors: Inom S. Normatov, Abulqosim Muminov, Parviz I. Normatov

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Problems of food security and the preservation of reserved zones in the region of Central Asia under the conditions of the climate change induced by the placement and construction of large reservoirs are considered. The criteria for the optimum placement and construction of reservoirs that entail the minimum impact on the environment are established. The need for the accounting of climatic parameters is shown by the calculation of the water quantity required for the irrigation of agricultural lands.

Keywords: adaptation, biodiversity, food security, water reservoir, risk

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