Search results for: scaling inhibition

Authors: William Creighton, Jan Smitheram

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Queer discourse has been tied to a middle-class, urban-centric, white approach to the discussion of queerness. In doing so, the multilayeredness of queer existence has been washed away in favour of palatable queer occupation. This paper uses design to explore a queer anti-urbanist approach to facilitate a more egalitarian architectural occupancy. Scott Herring’s work on queer anti-urbanism is key to this approach. Herring redeploys anti-urbanism from its historical understanding of open hostility, rejection and desire to destroy the city towards a mode of queer critique that counters normative ideals of homonormative metronormative gay lifestyles. He questions how queer identity has been closed down into a more diminutive frame where those who do not fit within this frame are subjected to persecution or silenced through their absence. We extend these ideas through design to ask how a queer anti-urbanist approach facilitates a more egalitarian architectural occupancy. Following a “design as research” methodology, the design outputs allow a vehicle to ask how we might live, otherwise, in architectural space. A design as research methodologically is a process of questioning, designing and reflecting – in a non-linear, iterative approach – establishes itself through three projects, each increasing in scale and complexity. Each of the three scales tackled a different body relationship. The project began exploring the relations between body to body, body to known others, and body to unknown others. Moving through increasing scales was not to privilege the objective, the public and the large scale; instead, ‘intra-scaling’ acts as a tool to re-think how scale reproduces normative ideas of the identity of space. There was a queering of scale. Through this approach, the results were an installation that brings two people together to co-author space where the installation distorts the sensory experience and forces a more intimate and interconnected experience challenging our socialized proxemics: knees might touch. To queer the home, the installation was used as a drawing device, a tool to study and challenge spatial perception, drawing convention, and as a way to process practical information about the site and existing house – the device became a tool to embrace the spontaneous. The final design proposal operates as a multi-scalar boundary-crossing through “private” and “public” to support kinship through communal labour, queer relationality and mooring. The resulting design works to set adrift bodies in a sea of sensations through a mix of pleasure programmes. To conclude, through three design proposals, this design research creates a relationship between queer anti-urbanism and design. It asserts that queering the design process and outcome allows a more inclusive way to consider place, space and belonging. The projects lend to a queer relationality and interdependence by making spaces that support the unsettled, out-of-place, but is it queer enough?

Keywords: queer, queer anti-urbanism, design as research, design

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Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

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Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

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Authors: Syed Dawood Md. Taimur, Md. Hasanur Rahman, Syeda Fahmida Afrin, Farzana Islam

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The concept of myocardial injury, although first recognized from animal studies, is now recognized as a clinical phenomenon that may result in microvascular damage, no-reflow phenomenon, myocardial stunning, myocardial hibernation and ischemic preconditioning. The final consequence of this event is left ventricular (LV) systolic dysfunction leading to increased morbidity and mortality. The typical clinical case of reperfusion injury occurs in acute myocardial infarction (MI) with ST segment elevation in which an occlusion of a major epicardial coronary artery is followed by recanalization of the artery. This may occur either spontaneously or by means of thrombolysis and/or by primary percutaneous coronary intervention (PCI) with efficient platelet inhibition by aspirin (acetylsalicylic acid), clopidogrel and glycoprotein IIb/IIIa inhibitors. In recent years, percutaneous coronary intervention (PCI) has become a well-established technique for the treatment of coronary artery disease. PCI improves symptoms in patients with coronary artery disease and it has been increasing the safety of procedures. However, peri- and post-procedural myocardial injury, including angiographical slow coronary flow, microvascular embolization, and elevated levels of cardiac enzyme, such as creatine kinase and troponin-T and -I, has also been reported even in elective cases. Furthermore, myocardial reperfusion injury at the beginning of myocardial reperfusion, which causes tissue damage and cardiac dysfunction, may occur in cases of the acute coronary syndrome. Because patients with myocardial injury is related to larger myocardial infarction and have a worse long-term prognosis than those without myocardial injury, it is important to prevent myocardial injury during and/or after PCI in patients with coronary artery disease. To date, many studies have demonstrated that adjunctive pharmacological treatment suppresses myocardial injury and increases coronary blood flow during PCI procedures. In this review, we highlight the usefulness of pharmacological treatment in combination with PCI in attenuating myocardial injury in patients with coronary artery disease.

Keywords: coronary artery disease, percutaneous coronary intervention, myocardial injury, pharmacology

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Authors: Yasmin Begum Mohammed

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Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

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Authors: Ming-Yeh Lu, Shiao-Shing Chen, Saikat Sinha Ray, Hung-Te Hsu

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Recently, anaerobic membrane bioreactors (AnMBRs) has been widely utilized, which combines anaerobic biological treatment process and membrane filtration, that can be present an attractive option for wastewater treatment and water reuse. Conventional AnMBR is having several advantages, such as improving effluent quality, compact space usage, lower sludge yield, without aeration and production of energy. However, the removal of nitrogen and phosphorus in the AnMBR permeate was negligible which become the biggest disadvantage. In recent years, forward osmosis (FO) is an emerging technology that utilizes osmotic pressure as driving force to extract clean water without additional external pressure. The pore size of FO membrane is kindly mentioned the pore size, so nitrogen or phosphorus could effectively improve removal of nitrogen or phosphorus. Anaerobic bioreactor with FO membrane (AnOMBR) can retain the concentrate organic matters and nutrients. However, phosphorus is a non-renewable resource. Due to the high rejection property of FO membrane, the high amount of phosphorus could be recovered from the combination of AnMBR and FO. In this study, development of novel submerged anaerobic osmotic membrane bioreactor integrated with periodic microfiltration (MF) extraction for simultaneous phosphorus and clean water recovery from wastewater was evaluated. A laboratory-scale AnOMBR utilizes cellulose triacetate (CTA) membranes with effective membrane area of 130 cm² was fully submerged into a 5.5 L bioreactor at 30-35℃. Active layer-facing feed stream orientation was utilized, for minimizing fouling and scaling. Additionally, a peristaltic pump was used to circulate draw solution (DS) at a cross flow velocity of 0.7 cm/s. Magnesium sulphate (MgSO₄) solution was used as DS. Microfiltration membrane periodically extracted about 1 L solution when the TDS reaches to 5 g/L to recover phosphorus and simultaneous control the salt accumulation in the bioreactor. During experiment progressed, the average water flux was achieved around 1.6 LMH. The AnOMBR process show greater than 95% removal of soluble chemical oxygen demand (sCOD), nearly 100% of total phosphorous whereas only partial removal of ammonia, and finally average methane production of 0.22 L/g sCOD was obtained. Therefore, AnOMBR system periodically utilizes MF membrane extracted for phosphorus recovery with simultaneous pH adjustment. The overall performance demonstrates that a novel submerged AnOMBR system is having potential for simultaneous wastewater treatment and resource recovery from wastewater, and hence, the new concept of this system can be used to replace for conventional AnMBR in the future.

Keywords: anaerobic treatment, forward osmosis, phosphorus recovery, membrane bioreactor

Procedia PDF Downloads 237

Authors: S. K. Ghosh, C. Srivastava, P. K. Limaye, V. Kain

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Electroplated hard chromium is widely known in coatings and surface finishing, automobile and aerospace industries because of its excellent hardness, wear resistance and corrosion properties. However, its precursor, Cr+6 is highly carcinogenic in nature and a consensus has been adopted internationally to eradicate this coating technology with an alternative one. The search for alternate coatings to electroplated hard chrome is continuing worldwide. Various alloys and nanocomposites like Co-W alloys, Ni-Graphene, Ni-diamond nanocomposites etc. have already shown promising results in this regard. Basically, in this study, electroless Ni-P alloys with excellent corrosion resistance was taken as the base matrix and incorporation of tungsten as third alloying element was considered to improve the hardness and wear resistance of the resultant alloy coating. The present work is focused on the preparation of Ni–W–P coatings by electrodeposition with different content of phosphorous and its effect on the electrochemical, mechanical and tribological performances. The results were also compared with Ni-W alloys. Composition analysis by EDS showed deposition of Ni-32.85 wt% W-3.84 wt% P (designated as Ni-W-LP) and Ni-18.55 wt% W-8.73 wt% P (designated as Ni-W-HP) alloy coatings from electrolytes containing of 0.006 and 0.01M sodium hypophosphite respectively. Inhibition of tungsten deposition in the presence of phosphorous was noted. SEM investigation showed cauliflower like growth along with few microcracks. The as-deposited Ni-W-P alloy coating was amorphous in nature as confirmed by XRD investigation and step-wise crystallization was noticed upon annealing at higher temperatures. For all the coatings, the nanohardness was found to increase after heat-treatment and typical nanonahardness values obtained for 400°C annealed samples were 18.65±0.20 GPa, 20.03±0.25 GPa, and 19.17±0.25 for alloy coatings Ni-W, Ni-W-LP and Ni-W-HP respectively. Therefore, the nanohardness data show very promising results. Wear and coefficient of friction data were recorded by applying a different normal load in reciprocating motion using a ball on plate geometry. Post experiment, the wear mechanism was established by detail investigation of wear-scar morphology. Potentiodynamic measurements showed coating with a high content of phosphorous was most corrosion resistant in 3.5wt% NaCl solution.

Keywords: corrosion, electrodeposition, nanohardness, Ni-W-P alloy coating

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Authors: Adeyi Akindele Oluwatosin, Mustapha Kaosarat Keji, Ajisebiola Babafemi Siji, Adeyi Olubisi Esther, Damilohun Samuel Metibemu, Raphael Emuebie Okonji

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Envenoming by Echis ocellatus is potentially life-threatening due to severe hemorrhage, renal failure, and capillary leakage. These effects are attributed to snake venom metalloproteinases (SVMPs). Due to drawbacks in the use of antivenom, natural inhibitors from plants are of interest in studies of new antivenom treatment. Antagonizing effects of bioactive compounds of Moringa oleifera, a known antisnake plant, are yet to be tested against SVMPs of E. ocellatus (SVMP-EO). Ethanol crude extract of M. oleifera was partitioned using n-hexane and ethyl acetate. Each partition was fractionated using column chromatography and tested against SVMP-EO purified through ion-exchange chromatography with EchiTab-PLUS polyvalent anti-venom as control. Phytoconstituents of ethyl acetate fraction were screened against the catalytic site of crystal of BaP1-SVMP, while drug-likeness and ADMET toxicity of compound were equally determined. The molecular weight of isolated SVMP-EO was 43.28 kDa, with a specific activity of 245 U/ml, a percentage yield of 62.83 %, and a purification fold of 0.920. The Vmax and Km values are 2 mg/ml and 38.095 μmol/ml/min, respectively, while the optimal pH and temperature are 6.0 and 40°C, respectively. Polyvalent anti-venom, crude extract, and ethyl acetate fraction of M. oleifera exhibited a complete inhibitory effect against SVMP-EO activity. The inhibitions of the P-1 and P-II metalloprotease’s enzymes by the ethyl acetate fraction are largely due to methanol, 6, 8, 9-trimethyl-4-(2-phenylethyl)-3-oxabicyclo[3.3.1]non-6-en-1-yl)- and paroxypropione, respectively. Both compounds are potential drug candidates with little or no concern of toxicity, as revealed from the in-silico predictions. The inhibitory effects suggest that this compound might be a therapeutic candidate for further exploration for treatment of Ocellatus’ envenoming.

Keywords: Echis ocellatus, Moringa oleifera, anti-venom, metalloproteases, snakebite, molecular docking

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Authors: Meksem Amara Leila, Ferfar Meriem, Meksem Nabila, Djebar Mohammed Reda

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The wheat is the cereal the most consumed in the world. In Algeria, the production of this cereal covers only 20 in 25 % of the needs for the country, the rest being imported. To improve the efficiency and the productivity of the durum wheat, the farmers turn to the use of pesticides: weed-killers, fungicides and insecticides. However this use often entrains losses of products more at least important contaminating the environment and all the food chain. Weed-killers are substances developed to control or destroy plants considered unwanted. That they are natural or produced by the human being (molecule of synthesis), the absorption and the metabolization of weed-killers by plants cause the death of these plants.In this work, we set as goal the evaluation of the effect of a weed-killer sulfonylurea, the CossackOD with various concentrations (0, 2, 4 and 9 µg) on variety of Triticum durum: Cirta. We evaluated the plant growth by measuring the leaves and root length, compared with the witness as well as the content of proline and analyze the level of one of the antioxydative enzymes: catalse, after 14 days of treatment. Sulfonylurea is foliar and root weed-killers inhibiting the acetolactate synthase: a vegetable enzyme essential to the development of the plant. This inhibition causes the ruling of the growth then the death. The obtained results show a diminution of the average length of leaves and roots this can be explained by the fact that the ALS inhibitors are more active in the young and increasing regions of the plant, what inhibits the cellular division and talks a limitation of the foliar and root’s growth. We also recorded a highly significant increase in the proline levels and a stimulation of the catalase activity. As a response to increasing the herbicide concentrations a particular increases in antioxidative mechanisms in wheat cultivar Cirta suggest that the high sensitivity of Cirta to this sulfonylurea herbicide is related to the enhanced production and oxidative damage of reactive oxygen species.

Keywords: sulfonylurea, Triticum durum, oxydative stress, Toxicity

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Authors: Hallal Nouria, Kharoubi Omar

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Wormwood (Artemisia absinthium L.) is a medicinal and aromatic bitter herb, which has been used as a medicine from ancient times. It has traditionally been used as anthelmintic, choleretic, antiseptic, balsamic, depurative, digestive, diuretic, emmenagogue and in treating leukemia and sclerosis. The species was cited to be used externally as cataplasm of crushed leaves for snake and scorpion bites or decoction for wounds and sores applied locally as antiseptic and antifungal. Wormwood extract have high contents of total phenolic compounds and total flavonoids indicating that these compounds contribute to antiradical and antioxidative activity. Most of the degenerative diseases are caused by free radicals. Antioxidants are the agents responsible for scavenging free radicals. The aim of present study was to evaluate the phytochemical and in vitro antioxidant properties of Wormwood extract. DPPH assay and reducing power assay were the method adopted to study antioxidant potentials of extracts. Standard methods were used to screen preliminary phytochemistry and quantitative analysis of tannin, phenolics and flavanoids. Aqueous and alcoholic extracts were showed good antioxidant effect with IC50 ranges from 62 μg/ml for aqueous and 116μg/ml for alcoholic extracts. Phenolic compounds, tannins and flavonoids were the major phytochemicals present in both the extracts. Percentage of inhibition increased with the increased concentration of extracts. The aqueous and alcoholic extract yielded 20, 15& 3, 59 mg/g gallic acid equivalent phenolic content 2, 78 & 1,83 mg/g quercetin equivalent flavonoid and 2, 34 & 6, 40 g tannic acid equivalent tannins respectively. The aqueous and methanol extracts of the aerial parts showed a positive correlation between the total phenolic content and the antioxidant activity measured in the plant samples. The present study provides evidence that both extracts of Artemisia absinthium is a potential source of natural antioxidant.

Keywords: pharmaceutical industries, medicinal and aromatic plant, antioxidants, phenolic compounds, Artemisia absinthium

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Authors: KuiDong Kang, Hye Bin Yim, Su Ah Kim

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Purpose: Tectorigenin is an isoflavone derived from the rhizome of Belamacanda chinensis. In this study, oxygen-induced retinopathy was used to characterize the anti-angiogenic properties of tectorigenin in mice. Methods: ICR neonatal mice were exposed to 75% oxygen from postnatal day P7 until P12 and returned to room air (21% oxygen) for five days (P12 to P17). Mice were subjected to daily intraperitoneal injection of tectorigenin (1 mg/kg, 10 mg/kg) and vehicle from P12 to P17. Retro-orbital injection of FITC-dextran was performed and retinal flat mounts were viewed by fluorescence microscopy. The Central avascular area was quantified from the digital images in a masked fashion using image analysis software (NIH ImageJ). Neovascular tufts were quantified by using SWIFT_NV and neovascular lumens were quantified from a histologic section in a masked fashion. Immunohistochemistry and Western blot analysis were also performed to demonstrate the anti-angiogenic activity of this compound in vivo. Results: In the retina of tectorigenin injected mouse (10mg/kg), the central non-perfusion area was significantly decreased compared to the vehicle injected group (1.76±0.5 mm2 vs 2.85±0.6 mm2, P<0.05). In vehicle-injected group, 33.45 ± 5.51% of the total retinal area was avascular, whereas the retinas of pups treated with high-dose (10 mg/kg) tectorigenin showed avascular retinal areas of 21.25 ±4.34% (P<0.05). High dose of tectorigenin also significantly reduced the number of vascular lumens in the histologic section. Tectorigenin (10 mg/kg) significantly reduced the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), MMP-9, and angiotensin II compared to the vehicle injected group. Tectorigenin did not affect CD31 abundance at any tested dose. Conclusions: Our results show that tectorigenin possesses powerful anti-angiogenic properties and can attenuate new vessel formation in the retina after systemic administration. These results imply that this compound can be considered as a candidate substance for therapeutic inhibition of retinal angiogenesis.

Keywords: tectorigenin, anti-angiogenic, retinopathy, Belamacanda chinensis

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Authors: Eman Abdullah Morsi, Hend Okasha, Heba Abdel Hady, Mortada El-Sayed, Mohamed Abbas Shemis

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Context: Linum usitatissimum (Linn), known as Flaxseed, is one of the most important medicinal plants traditionally used for various health as nutritional purposes. Objective: Estimation of total phenolic and flavonoid contents as well as evaluate the antioxidant using α, α-diphenyl-β-picrylhydrazyl (DPPH), 2-2'azinobis (3-ethylbenzthiazoline-6-sulphonic acid (ABTS) and total antioxidant capacity (TAC) assay and investigation of anti-inflammatory by Bovine serum albumin (BSA) and anticancer activities of hepatocellular carcinoma cell line (HepG2) and breast cancer cell line (MCF7) have been applied on hexane, ethyl acetate, n-butanol and methanol extracts and also, fractions of methonal extract (hexane, ethyl acetate and n-butanol). Materials and Methods: Phenolic and flavonoid contents were detected using spectrophotometric and colorimetric assays. Antioxidant and anti-inflammatory activities were estimated in-vitro. Anticancer activity of extracts and fractions of methanolic extract were tested on (HepG2) and (MCF7). Results: Methanolic extract and its ethyl acetate fraction contain higher contents of total phenols and flavonoids. In addition, methanolic extract had higher antioxidant activity. Butanolic and ethyl acetate fractions yielded higher percent of inhibition of protein denaturation. Meanwhile, ethyl acetate fraction and methanolic extract had anticancer activity against HepG2 and MCF7 (IC50=60 ± 0.24 and 29.4 ± 0.12µg.mL⁻¹) and (IC50=94.7 ± 0.21 and 227 ± 0.48µg.mL⁻¹), respectively. In Gas chromatography-mass spectrometry (GC-MS) analysis, methanolic extract has 32 compounds, whereas; ethyl acetate and butanol fractions contain 40 and 36 compounds, respectively. Conclusion: Flaxseed contains totally different biologically active compounds that have been found to possess good variable activities, which can protect human body against several diseases.

Keywords: phenolic content, flavonoid content, HepG2, MCF7, hemolysis-assay, flaxseed

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Authors: S. K. Thind, Aparjot Kaur

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Heat stress is one of the major environmental factors drastically reducing wheat production. Crop heat tolerance can be enhanced by preconditioning of plants by exogenous application of osmoprotectants. Presently, the effect of trehalose pretreatment (at 1 mM, and 1.5 nM) under heat stress of 35±2˚C (moderate) and 40±2˚ (severe) for four and eight hour was conducted in wheat (Tricticum aestivum L.) genotypes viz. HD2967, PBW 175, PBW 343, PBW 621, and PBW 590. Heat stress affects wide spectrum of physiological processes within plants that are irreversibly damaged by stress. Membrane thermal stability (MTS) and cell viability was significantly decreased under heat stress for eight hours. Pretreatment with trehalose improved MTS and cell viability under stress and this effect was more promotory with higher concentration. Thermal stability of photosynthetic apparatus differed markedly between genotypes and Hill reaction activity was recorded more in PBW621 followed by C306 as compared with others. In all genotypes photolysis of water showed decline with increase in temperature stress. Trehalose pretreatment helped in sustaining Hill reaction activity probably by stabilizing the photosynthetic apparatus against heat-induced photo inhibition. Both plant growth and development were affected by temperature in both shoot and root under heat stress. The reduction was compensated partially by trehalose (1.5 mM) application. Adaption to heat stress is associated with the metabolic adjustment which led to accumulation of soluble sugars including non-reducing and reducing for their role in adaptive mechanism. Higher acid invertase activity in shoot of tolerant genotypes appeared to be a characteristic for stress tolerance. As sucrose synthase play central role in sink strength and in studied wheat genotype was positively related to dry matter accumulation. The duration of heat stress for eight hours had more severe effect on these parameters and trehalose application at 1.5 mM ameliorated it to certain extent.

Keywords: heat stress, Triticum aestivum, trehalose, membrane thermal stability, triphenyl tetrazolium chloride, reduction test, growth, sugar metabolism

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Authors: Farid Khosravikia, Patricia Clayton

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The main objective of this work is to evaluate the advantages and disadvantages of various machine learning techniques in two key steps of seismic hazard and risk assessment of different types of structures. The first step is the development of ground-motion models, which are used for forecasting ground-motion intensity measures (IM) given source characteristics, source-to-site distance, and local site condition for future events. IMs such as peak ground acceleration and velocity (PGA and PGV, respectively) as well as 5% damped elastic pseudospectral accelerations at different periods (PSA), are indicators of the strength of shaking at the ground surface. Typically, linear regression-based models, with pre-defined equations and coefficients, are used in ground motion prediction. However, due to the restrictions of the linear regression methods, such models may not capture more complex nonlinear behaviors that exist in the data. Thus, this study comparatively investigates potential benefits from employing other machine learning techniques as statistical method in ground motion prediction such as Artificial Neural Network, Random Forest, and Support Vector Machine. The results indicate the algorithms satisfy some physically sound characteristics such as magnitude scaling distance dependency without requiring pre-defined equations or coefficients. Moreover, it is shown that, when sufficient data is available, all the alternative algorithms tend to provide more accurate estimates compared to the conventional linear regression-based method, and particularly, Random Forest outperforms the other algorithms. However, the conventional method is a better tool when limited data is available. Second, it is investigated how machine learning techniques could be beneficial for developing probabilistic seismic demand models (PSDMs), which provide the relationship between the structural demand responses (e.g., component deformations, accelerations, internal forces, etc.) and the ground motion IMs. In the risk framework, such models are used to develop fragility curves estimating exceeding probability of damage for pre-defined limit states, and therefore, control the reliability of the predictions in the risk assessment. In this study, machine learning algorithms like artificial neural network, random forest, and support vector machine are adopted and trained on the demand parameters to derive PSDMs for them. It is observed that such models can provide more accurate estimates of prediction in relatively shorter about of time compared to conventional methods. Moreover, they can be used for sensitivity analysis of fragility curves with respect to many modeling parameters without necessarily requiring more intense numerical response-history analysis.

Keywords: artificial neural network, machine learning, random forest, seismic risk analysis, seismic hazard analysis, support vector machine

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Authors: Benlaifa Meriem, Berredjem Hajira, Bouasla Radia, Berredjem Malika, Djebar Med Reda

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Toxoplasmosis is a cosmopolitan infection due to Toxoplasma gondii (T.gondii). It is a significant cause of congenital disease and an important opportunistic pathogen which has become a worldwide increasing problem due to the AIDS epidemic. Current available drugs do not give satisfactory results and often have only a static and several adverse side effects as it is the case of pyrimethamine. So, the need to develop and evaluate new drugs is critical. The purpose of this study is to investigate the in vitro and in vivo effects of the new chiral N-acylsulfonamide bis-oxazolidin-2-ones on T.gondii. In this study, anti-T.gondii RH strain activities, of two new chiral N-acylsulfonamide bis-oxazolidin-2-ones were evaluated in vitro, using a MRC-5 fibroblast tissue cultures to determine the concentration that inhibit parasite multiplication by 50% (IC50) of each drug and in vivo, by PCR detection of the tachyzoites in mice ascites after new molecules treatment, using the 35-fold repetitive B1 gene of T.gondii. The in vitro results demonstrated that the treatment with the tested molecules decreased the amount of tachyzoites in cell culture in a dose-dependent manner. The inhibition was complete for concentrations over 4 mg/ml. The IC50 of Mol 1 and Mol 2 were 1.5 and 3 mg/ml, respectively, and were quite similar to the control one (2 mg/ml). The Mol 1 was highly active against T.gondii in cell cultures than Mol 2; these results were similar to those of sulfadiazine-treated group (p < 0.05). Toxoplasma-specific DNA was demonstrated in all ascites samples from infected mice of the different tested groups. Mol 1 showed better effect than Mol 2, but it did not completely inhibit the parasite proliferation. The intensity of amplification products increased when the treatment started late after infection. These findings suggest continuous parasite replication despite the treatment. In conclusion, our results showed a promising treatment effect of the tested molecules and suggest that in vitro, the Mol 1, and Mol 2 have a dose-dependent effect and a high cytotoxicity on the studied cells. The present study revealed that concentration and duration of tested molecules treatment are major factors that influence the course of Toxoplasma infection in infected mice.

Keywords: cytotoxicity, PCR, sulfonamide, Toxoplasma gondii

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Authors: Aoxue Yang, Weili Tian, Yonghe Wu, Haikun Liu

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Brain tumor stem cells (BTSCs) are resistant to therapy and give rise to recurrent tumors. These rare and elusive cells are likely to disseminate during cancer progression, and some may enter dormancy, remaining viable but not increasing. The identification of dormant BTSCs is thus necessary to design effective therapies for glioblastoma (GBM) patients. Little progress has been made in therapeutic treatment of glioblastoma in the last decade despite rapid progress in molecular understanding of brain tumors1. Here we show that the stress hormone glucocorticoid is essential for the maintenance of brain tumor stem cells (BTSCs), which are resistant to conventional therapy. The glucocorticoid receptor (GR) regulates metabolic plasticity and chemoresistance of the dormant BTSC via controlling expression of GPD1 (glycerol-3-phosphate dehydrogenase 1), which is an essential regulator of lipid metabolism in BTSCs. Genomic, lipidomic and cellular analysis confirm that GR/GPD1 regulation is essential for BTSCs metabolic plasticity and survival. We further demonstrate that the GR agonist dexamethasone (DEXA), which is commonly used to control edema in glioblastoma, abolishes the effect of chemotherapy drug temozolomide (TMZ) by upregulating GPD1 and thus promoting tumor cell dormancy in vivo, this provides a mechanistic explanation and thus settle the long-standing debate of usage of steroid in brain tumor patient edema control. Pharmacological inhibition of GR/GPD1 pathway disrupts metabolic plasticity of BTSCs and prolong animal survival, which is superior to standard chemotherapy. Patient case study shows that GR antagonist mifepristone blocks tumor progression and leads to symptomatic improvement. This study identifies an important mechanism regulating cancer stem cell dormancy and provides a new opportunity for glioblastoma treatment.

Keywords: cancer stem cell, dormancy, glioblastoma, glycerol-3-phosphate dehydrogenase 1, glucocorticoid receptor, dexamethasone, RNA-sequencing, phosphoglycerides.

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Authors: Yevheniia Varyvoda, Douglas Taren

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At the aggregate level, climate variability, the rising number of active violent conflicts, globalization and industrialization of agriculture, the loss in diversity of crop species, the increase in demand for agricultural production, and the adoption of healthy and sustainable dietary patterns are exacerbating factors of food system destabilization. The importance of pseudocereals to fuel and sustain resilient food systems is recognized by leading organizations working to end hunger, particularly for their critical capability to diversify livelihood portfolios and provide plant-sourced healthy nutrition in the face of systemic shocks and stresses. Amaranth, buckwheat, and quinoa are the most promising and used pseudocereals for ensuring food system resilience in the reality of climate change due to their high nutritional profile, good digestibility, palatability, medicinal value, abiotic stress tolerance, pest and disease resistance, rapid growth rate, adaptability to marginal and degraded lands, high genetic variability, low input requirements, and income generation capacity. The study provides the rationale and examples of advancing local and regional food systems' resilience by scaling up the utilization of amaranth, buckwheat, and quinoa along all components of food systems to architect indirect nutrition interventions and climate-smart approaches. Thus, this study aims to explore the drivers for ancient pseudocereal utilization, the potential resilience benefits that can be derived from using them, and the challenges and opportunities for pseudocereal utilization within the food system components. The PSALSAR framework regarding the method for conducting systematic review and meta-analysis for environmental science research was used to answer these research questions. Nevertheless, the utilization of pseudocereals has been slow for a number of reasons, namely the increased production of commercial and major staples such as maize, rice, wheat, soybean, and potato, the displacement due to pressure from imported crops, lack of knowledge about value-adding practices in food supply chain, limited technical knowledge and awareness about nutritional and health benefits, absence of marketing channels and limited access to extension services and information about resilient crops. The success of climate-resilient pathways based on pseudocereal utilization underlines the importance of co-designed activities that use modern technologies, high-value traditional knowledge of underutilized crops, and a strong acknowledgment of cultural norms to increase community-level economic and food system resilience.

Keywords: resilience, pseudocereals, food system, climate change

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Authors: Sukumar Namineni, Tracy O'Connor, Ulrich Kalinke, Percy Knolle, Mathias Heikenwaelder

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The liver is one of the pivotal organs in vertebrate animals, serving a multitude of functions such as metabolism, detoxification and protein synthesis and including a predominant role in innate immunity. The innate immune mechanisms pertaining to liver in controlling viral infections have largely been attributed to the Kupffer cells, the locally resident macrophages. However, all the cells of liver are equipped with innate immune functions including, in particular, the hepatocytes. Hence, our aim in this study was to elucidate the innate immune contribution of hepatocytes in viral clearance using mice lacking Ikkβ specifically in the hepatocytes, termed IkkβΔᴴᵉᵖ mice. Blockade of Ikkβ activation in IkkβΔᴴᵉᵖ mice affects the downstream signaling of canonical NF-κB signaling by preventing the nuclear translocation of NF-κB, an important step required for the initiation of innate immune responses. Interestingly, infection of IkkβΔᴴᵉᵖ mice with lymphocytic choriomeningitis virus (LCMV) led to strongly increased hepatic viral titers – mainly confined in clusters of infected hepatocytes. This was due to reduced interferon stimulated gene (ISG) expression during the onset of infection and a reduced CD8+ T-cell-mediated response. Decreased ISG production correlated with increased liver LCMV protein and LCMV in isolated hepatocytes from IkkβΔᴴᵉᵖ mice. A similar phenotype was found in LCMV-infected mice lacking interferon signaling in hepatocytes (IFNARΔᴴᵉᵖ) suggesting a link between NFkB and interferon signaling in hepatocytes. We also observed a failure of interferon-mediated inhibition of HBV replication in HepaRG cells treated with NF-kB inhibitors corroborating our initial findings with LCMV infections. Collectively, these results clearly highlight a previously unknown and influential role of hepatocytes in the induction of innate immune responses leading to viral clearance during a systemic viral infection with LCMV-WE.

Keywords: CD8+ T cell responses, innate immune mechanisms in the liver, interferon signaling, interferon stimulated genes, NF-kB signaling, viral clearance

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Authors: Andy Sand, Naama Massad – Ivanir, Nadav Nitzan, Elisa Valderrama, Alfred Wegenberger, Koranit Shlosman, Rotem Shemesh, Ester Segal

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Microbial spoilage of food products is of great concern in the food industry due to the direct impact on the shelf life of foods and the risk of foodborne illness. Therefore, food packaging may serve as a crucial contribution to keep the food fresh and suitable for consumption. Active packaging solutions that have the ability to inhibit the development of microorganism in food products attract a lot of interest, and many efforts have been made to engineer and assimilate such solutions on various food products. NanoPack is an EU-funded international project aiming to develop state-of-the-art antimicrobial packaging systems for perishable foods. The project is based on natural essential oils which possess significant antimicrobial activity against many bacteria, yeasts and molds. The essential oils are encapsulated in natural aluminosilicate clays, halloysite nanotubes (HNT's), that serves as a carrier for the volatile essential oils and enable their incorporation into polymer films. During the course of the project, several polyethylene films with diverse essential oils combinations were designed based on the characteristics of their target food products. The antimicrobial activity of the produced films was examined in vitro on a broad spectrum of microorganisms including gram-positive and gram-negative bacteria, aerobic and anaerobic bacteria, yeasts and molds. The films that showed promising in vitro results were successfully assimilated on in vivo active packaging of several food products such as cheese, bread, fruits and raw meat. The results of the in vivo analyses showed significant inhibition of the microbial spoilage, indicating the strong contribution of the NanoPack packaging solutions on the extension of shelf life and reduction of food waste caused by early spoilage throughout the supply chain.

Keywords: food safety, food packaging, essential oils, nanotechnology

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Authors: Bipasa Dey, Varsha Panwar, Tanmay Dutta

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Laccase, a multicopper oxidase (EC 1.10.3.2) have been at the forefront as a superior industrial biocatalyst. They are versatile in terms of bestowing sustainable and ecological catalytic reactions such as polymerisation, xenobiotic degradation and bioremediation of phenolic and non-phenolic compounds. Regardless of the wide biotechnological applications, the critical limiting factors viz. reusability, retrieval, and storage stability still prevail. This can cause an impediment in their applicability. Crosslinked enzyme aggregates (CLEAs) have emerged as a promising technique that rehabilitates these essential facets, albeit at the expense of their enzymatic activity. The carrier free crosslinking method prevails over the carrier-bound immobilisation in conferring high productivity, low production cost owing to the absence of additional carrier and circumvent any non-catalytic ballast which could dilute the volumetric activity. To the best of our knowledge, the ε-amino group of lysyl residue is speculated as the best choice for forming Schiff’s base with glutaraldehyde. Despite being most preferrable, excess glutaraldehyde can bring about disproportionate and undesirable crosslinking within the catalytic site and hence could deliver undesirable catalytic losses. Moreover, the surface distribution of lysine residues in Trametes versicolor laccase is significantly less. Thus, to mitigate the adverse effect of glutaraldehyde in conjunction with scaling down the degradation or catalytic loss of the enzyme, crosslinking with inert substances like gelatine, collagen, Bovine serum albumin (BSA) or excess lysine is practiced. Analogous to these molecules, sugars have been well known as a protein stabiliser. It helps to retain the structural integrity, specifically secondary structure of the protein during aggregation by changing the solvent properties. They are comprehended to avert protein denaturation or enzyme deactivation during precipitation. We prepared crosslinked enzyme aggregates (CLEAs) of laccase from T. versicolor with the aid of sugars. The sugar CLEAs were compared with the classic BSA and glutaraldehyde laccase CLEAs concerning physico-chemical properties. The activity recovery for the fructose CLEAs were found to be ~20% higher than the non-sugar CLEA. Moreover, the 𝐾𝑐𝑎𝑡𝐾𝑚⁄ values of the CLEAs were two and three-fold higher than BSA-CLEA and GACLEA, respectively. The half-life (t1/2) deciphered by sugar-CLEA was higher than the t1/2 of GA-CLEAs and free enzyme, portraying more thermal stability. Besides, it demonstrated extraordinarily high pH stability, which was analogous to BSA-CLEA. The promising attributes of increased storage stability and recyclability (>80%) gives more edge to the sugar-CLEAs over conventional CLEAs of their corresponding free enzyme. Thus, sugar-CLEA prevails in furnishing the rudimentary properties required for a biocatalyst and holds many prospects.

Keywords: cross-linked enzyme aggregates, laccase immobilization, enzyme reusability, enzyme stability

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Authors: Anne M. Denton, Rahul Gomes, David W. Franzen

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High-resolution elevation data are becoming increasingly available, but typical approaches for computing topographic features, like slope and curvature, still assume small sliding windows, for example, of size 3x3. That means that the digital elevation model (DEM) has to be resampled to the scale of the landform features that are of interest. Any higher resolution is lost in this resampling. When the topographic features are computed through regression that is performed at the resolution of the original data, the accuracy can be much higher, and the reported result can be adjusted to the length scale that is relevant locally. Slope and variance are calculated for overlapping windows, meaning that one regression result is computed per raster point. The number of window centers per area is the same for the output as for the original DEM. Slope and variance are computed by performing regression on the points in the surrounding window. Such an approach is computationally feasible because of the additive nature of regression parameters and variance. Any doubling of window size in each direction only takes a single pass over the data, corresponding to a logarithmic scaling of the resulting algorithm as a function of the window size. Slope and variance are stored for each aggregation step, allowing the reported slope to be selected to minimize variance. The approach thereby adjusts the effective window size to the landform features that are characteristic to the area within the DEM. Starting with a window size of 2x2, each iteration aggregates 2x2 non-overlapping windows from the previous iteration. Regression results are stored for each iteration, and the slope at minimal variance is reported in the final result. As such, the reported slope is adjusted to the length scale that is characteristic of the landform locally. The length scale itself and the variance at that length scale are also visualized to aid in interpreting the results for slope. The relevant length scale is taken to be half of the window size of the window over which the minimum variance was achieved. The resulting process was evaluated for 1-meter DEM data and for artificial data that was constructed to have defined length scales and added noise. A comparison with ESRI ArcMap was performed and showed the potential of the proposed algorithm. The resolution of the resulting output is much higher and the slope and aspect much less affected by noise. Additionally, the algorithm adjusts to the scale of interest within the region of the image. These benefits are gained without additional computational cost in comparison with resampling the DEM and computing the slope over 3x3 images in ESRI ArcMap for each resolution. In summary, the proposed approach extracts slope and aspect of DEMs at the lengths scales that are characteristic locally. The result is of higher resolution and less affected by noise than existing techniques.

Keywords: high resolution digital elevation models, multi-scale analysis, slope calculation, window-based regression

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Authors: Bouchiha Hanene, Rouabhi Rachid, Bouchama Khaled, Djebar Berrebbah Houraya, Djebar Mohamed Reda

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Recently, some natural products such as essentials oils (EOs) have been used in the fields as alternative to synthetic compounds, to minimize the negative impacts to the environment. This fact has led to questions about the possible impact of EOs on ecosystems. Currently in toxicology, the use of alternative models can help to understand the mechanisms of toxic action, at different levels of organization of ecosystems. Algae, protozoa and bacteria form the base of the food chain and protozoan cells are used as bioindicators often of pollution in environment. Unicellular organisms offer the possibility of direct study of independent cells with specific characteristics of individual cells and whole organisms at the same time. This unicellular facilitates the study of physiological processes, and effects of pollutants at the cellular level, which makes it widely used to assess the toxic effects of various xenobiotics. This study aimed to verify the effects of EOs of one famous plant used tremendously in our folk medicine, namely Artemisia herba alba in causing acute toxicity (24 hours) and chronic (15 days) toxicity for model cellular (Paramecium sp). To this end, cellular’s of paramecium were exposed to various concentrations (Three doses were chosen) of EOs extracted from plant (Artemisia herba alba). In the first experiment, the cellular s cultures were exposed for 48 hours to different concentrations to determine the median lethal concentration (DL50). We followed the evolution of physiological parameters (growth), biochemical (total proteins, respiratory metabolism), as well as the variations of a bio marker the GSH. Our results highlighted a light inhibition of the growth of the protozoa as well as a disturbance of the contents of total proteins and a reduction in the reduced rate of glutathione. The polarographic study revealed a stimulation of the consumption of O2 and this at the treated cells.

Keywords: essential oils, protozoa, bio indicators, toxicity, Growth, bio marker, proteins, polarographic

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Authors: Anna-Mari Kok, Carel B. Oosthuizen, Namrita Lall

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Tuberculosis (TB) is a disease caused by the bacterial pathogen Mycobacterium tuberculosis. It is associated with high mortality rates in both developing and developed countries. Many higher plants are found that are medicinally associated with tuberculosis infection. Plants belonging to thirteen families were selected, based on their traditional usage for tuberculosis and its associated symptoms. Eight plants showed the best antimycobacterial activities (MIC-value ≤ 500.0 µg/ml) against M. tuberculosis H37Rv. LS was found to have a minimum inhibitory concentration (MIC) of 125 µg/ml whereas, Tulbaghia violacea, Heteromorpha arborescens, Sutherlandia frutescens, Eucalyptus deglupta, and Plectranthus neochilus were found to have a MIC value of 250 µg/ml against M. tuberculosis H37Rv. Cytotoxicity values on U937 and HepG2 cells were obtained and the IC50 values ranged between 40 ±4.30 and > 400 µg/ml for the U937 cell line and 72.4 ±1.50 and > 400 µg/ml for the HepG2 cell line. Heteromorpha arborescens had the lowest IC50 value in both cell lines and therefore showed moderate levels of toxicity. Of the 19 samples that underwent the 2, 2- diphenyl- 1- picrylhydrazyl (DPPH) antioxidant assay, Eucalyptus deglupta and Melianthus major showed significant free radical scavenging activities with concentrations of 1.33 and 1.32 µg/ml respectively for the inhibition of DPPH. Hepatotoxicity induced by acetaminophen identified Searsia lancea with hepatoprotective activity of 59.37% at a ¼ IC50 concentration. Out of the 7 samples that were investigated for their immunomodulatory capabilities, Eucalyptus deglupta produced the most IL-12 with Sutherlandia frutescens also showing positive results for IL-12 production. In the present study, Eucalyptus deglupta showed the most promising results with good activity against M. tuberculosis with an MIC-value of 250 µg/ml. It also has potent antioxidant activity with an IC50 value of 1.33 µg/ml. This sample also stimulated high production of the cytokine, IL-12. Searsia lancea showed moderate antimycobacterial acticvity with an MIC-value of 500 µg/ml. The antioxidant potential also showed promising results with an IC50 value of 4.50 µg/ml. The hepatoprotective capability of Searsia lancea was 59.34% at a ¼ IC50 concentration. Another sample Sutherlandia frutescens showed effective antimycobacterial activity with an MIC-value of 250 µg/ml. It also stimulated production of IL-12 with 13.43 pg/ml produced. These three samples can be considered for further studies for the consideration as adjuvants for current tuberculosis treatment.

Keywords: adjuvant, hepatoprotection, immunomodulation, tuberculosis

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Authors: Govindan Sudha, Mathumitha Subramaniam, Alamelu Govindasamy, Sasikala Gunasekaran

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The aim of this study was to investigate the protective effect of Hypsizygus ulmarius polysaccharides (HUP) on reducing oxidative stress, cognitive impairment and neurotoxicity in D-galactose induced aging mice. Mice were subcutaneously injected with D-galactose (150 mg/kg per day) for 6 weeks and were administered HUP simultaneously. Aged mice receiving vitamin E (100 mg/kg) served as positive control. Chronic administration of D-galactose significantly impaired cognitive performance oxidative defence and mitochondrial enzymes activities as compared to control group. The results showed that HUP (200 and 400 mg/kg) treatment significantly improved the learning and memory ability in Morris water maze test. Biochemical examination revealed that HUP significantly increased the decreased activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), mitochondrial enzymes-NADH dehydrogenase, malate dehydrogenase (MDH), isocitrate dehydrogenase (ICDH), Na+K+, Ca2+, Mg2+ATPase activities, elevated the lowered total anti-oxidation capability (TAOC), glutathione (GSH), vitamin C and decreased the raised acetylcholinesterase (AChE) activities, malondialdehyde (MDA), hydroperoxide (HPO), protein carbonyls (PCO), advanced oxidation protein products (AOPP) levels in brain of aging mice induced by D-gal in a dose-dependent manner. In conclusion, present study highlights the potential role of HUP against D-galactose induced cognitive impairment, biochemical and mitochondrial dysfunction in mice. In vitro studies on the effect of HUP on scavenging DPPH, ABTS, DMPD, OH radicals, reducing power, B-carotene bleaching and lipid peroxidation inhibition confirmed the free radical scavenging and antioxidant activity of HUP. The results suggest that HUP possesses anti-aging efficacy and may have potential in treatment of neurodegenerative diseases.

Keywords: aging, antioxidants, mushroom, neurotoxicity

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Authors: Chinedu F. Anochie

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The deterioration of materials as a result of their interaction with the environment has been a huge challenge to engineering. Many steps have been taking to tackle corrosion and its effects on harmful effects on engineering materials and structures. Corrosion inhibition, coating, passivation, materials selection, and cathodic protection are some of the methods utilized to curtail the rate at which materials corrode. The use of sacrificial anodes (magnesium, aluminum, or zinc) to protect the metal of interest is a widespread technique used to prevent corrosion in underground structures, ship hauls, and other structures susceptible to corrosion attack. However, certain factors, like resistivity, affect the performance of sacrificial anodes. To establish the effect of soil resistivity on the effectiveness of a cathodic protection system, a mild steel specimen was cathodically protected around Workshop 2 area, Federal University of Technology, Owerri, Nigeria. Design calculations showed that one zinc anode was sufficient to protect the pipe. The specimen (mild steel pipe) was coated with white and black polykene tapes and was subsequently buried in a high resistivity soil. The pipe-to-soil potential measurements were obtained using a digital fluke multimeter. The protection potential obtained on installation was higher than the minimum protection criteria. However, the potential results obtained over a fourteen-day intervals continually decreased to a value significantly lower than the minimum protection criteria. This showed that the sacrificial anode (zinc) was rendered ineffective by the high resistivity of the area of installation. It has been shown that the resistivity of the soil has a marked effect on the feasibility of cathodic protection systems. This work justified that zinc anode cannot be used for cathodic protection around Workshop 2 area, Federal University of Technology, Owerri, Nigeria, because of the high resistivity of the area. An experimental data which explains the effectiveness of galvanic anode cathodic protection system on corrosion control of a small steel structure, exposed to a soil of high resistivity has been established.

Keywords: cathodic protection, corrosion, pipe, sacrificial anode

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Authors: Adam M. Pitz, Gillian L. Phillipson, Jayant E. Khanolkar, Andrew M. Middleton

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New emerging evidence suggests that the nose is the predominant route for entry of the SARS-CoV-2 virus into the host. A virucidal suspension test (conforming in principle to the European Standard EN14476) was conducted to determine whether a commercial liquid gel intranasal spray containing 1% of the mucoadhesive hydroxypropyl methylcellulose (HPMC) could inhibit the cellular infectivity of the SARS-CoV-2 coronavirus. Virus was added to the test product samples and to controls in a 1:8 ratio and mixed with one part bovine serum albumin as an interfering substance. The test samples were pre-equilibrated to 34 ± 2°C (representing the temperature of the nasopharynx) with the temperature maintained at 34 ± 2°C for virus contact times of 1, 5 and 10 minutes. Neutralized aliquots were inoculated onto host cells (Vero E6 cells, ATCC CRL-1586). The host cells were then incubated at 36 ± 2°C for a period of 7 days. The residual infectious virus in both test and controls was detected by viral-induced cytopathic effect. The 50% tissue culture infective dose per mL (TCID50/mL) was determined using the Spearman-Karber method with results reported as the reduction of the virus titer due to treatment with test product, expressed as log10. The controls confirmed the validity of the results with no cytotoxicity or viral interference observed in the neutralized test product samples. The HPMC formulation reduced SARS-CoV-2 titer, expressed as log10TCID50, by 2.30 ( ± 0.17), 2.60 ( ± 0.19), and 3.88 ( ± 0.19) with the respective contact times of 1, 5 and 10 minutes. The results demonstrate that this 1% HPMC gel formulation can reduce the cellular infectivity of the SARS-CoV-2 virus with an increasing viral inhibition observed with increasing exposure time. This 1% HMPC gel is well tolerated and can reside, when delivered via nasal spray, for up to one hour in the nasal cavity. We conclude that this intranasal gel spray with 1% HPMC repeat-dosed every few hours may offer an effective preventive or early intervention solution to limit the transmission and impact of the SARS-CoV-2 coronavirus.

Keywords: hydroxypropyl methylcellulose, mucoadhesive nasal spray, respiratory viruses, SARS-CoV-2

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Authors: Sneha Singh, Abhimanyu Dev, Vinod Nigam

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The major issue which decides the impending use of gold nanoparticles (AuNPs) in nanobiotechnological applications is their particle size and stability. Often the AuNPs obtained biomimetically are considered useless owing to their instability in the aqueous medium and thereby limiting the widespread acceptance of this facile green synthesis procedure. So, the use of nontoxic surfactants is warranted to stabilize the biogenic nanoparticles (NPs). But does the surfactant only play a role in stabilizing by being adsorbed to the NPs surface or can it have any other significant contribution in synthesis process and controlling their size as well as shape? Keeping this idea in mind, AuNPs were synthesized by using surfactant treated (lechate) and untreated (cell lysate supernatant) Bacillus licheniformis cell extract. The cell extracts mediated reduction of chloroauric acid (HAuCl 4) in the presence of non-ionic surfactant, Tween 20 (TW20), and its effect on the AuNPs stability was studied. Interestingly, the surfactant used in the study served as potential alternative to harvest cellular enzymes involved in bioreduction process in a hassle free condition. The surfactants ability to solubilize/leach membrane proteins and simultaneously stabilizing the AuNPs could have advantage from process point of view as it will reduce the time and economics involve in the nanofabrication of biogenic NPs. The synthesis was substantiated with UV-Vis spectroscopy, Dynamic light scattering study, FTIR spectroscopy, and Transmission electron microscopy. The Zeta potential of AuNPs solutions was measured routinely to corroborate the stability observations recorded visually. Highly stable, ultra-small AuNPs of 2.6 nm size were obtained from the study. Further, the biological efficacy of the obtained AuNPs as potential antibacterial agent was evaluated against Bacilllus subtilis, Pseudomonas aeruginosa, and Escherichia coli by observing the zone of inhibition. This potential of AuNPs of size < 3 nm as antibacterial agent could pave way for development of new antimicrobials and overcoming the problems of antibiotics resistance

Keywords: antibacterial, bioreduction, nanoparticles, surfactant

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Authors: Sheraz Gul

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The requirements for progressing a compound to clinical trials is well established and relies on the results from in-vitro and in-vivo animal tests to indicate that it is likely to be safe and efficacious when testing in humans. The typical data package required will include demonstrating compound safety, toxicity, bioavailability, pharmacodynamics (potential effects of the compound on body systems) and pharmacokinetics (how the compound is potentially absorbed, distributed, metabolised and eliminated after dosing in humans). If the desired criteria are met and the compound meets the clinical Candidate criteria and is deemed worthy of further development, a submission to regulatory bodies such as the US Food & Drug Administration for an exploratory Investigational New Drug Study can be made. The purpose of this study is to collect data to establish that the compound will not expose humans to unreasonable risks when used in limited, early-stage clinical studies in patients or normal volunteer subjects (Phase I). These studies are also designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on their effectiveness. In order to reach the above goals, we have developed a pre-clinical high throughput Absorption, Distribution, Metabolism and Excretion–Toxicity (ADME–Toxicity) panel of assays to identify compounds that are likely to meet the Lead and Candidate compound acceptance criteria. This panel includes solubility studies in a range of biological fluids, cell viability studies in cancer and primary cell-lines, mitochondrial toxicity, off-target effects (across the kinase, protease, histone deacetylase, phosphodiesterase and GPCR protein families), CYP450 inhibition (5 different CYP450 enzymes), CYP450 induction, cardio-toxicity (hERG) and gene-toxicity. This panel of assays has been applied to multiple compound series developed in a number of projects delivering Lead and clinical Candidates and examples from these will be presented.

Keywords: absorption, distribution, metabolism and excretion–toxicity , drug discovery, food and drug administration , pharmacodynamics

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Authors: Parikshit Gogo, N. N. Dutta

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The oxidative enzymes specially laccase (benzenediol: oxygen oxidoreductase, E.C.1.10.3.2) from bacteria, fungi and plants have been playing an important role in green technologies due to their specific advantageous properties. Laccase from different sources and in different forms was used as a biocatalyst in many oxidation and conjugation reactions starting from phenol to hydrocarbons. Tea polyphenols and its derivatives attract the scientific community because of their potential use as antioxidants in food, pharmaceutical and cosmetic industries. Conjugate of polyphenols emerged as a novel materials which shows better stability and antioxidant properties in applied fields. The conjugation reaction of catechin with poly (allylamine) has been studied using free, immobilized and cross-linked enzyme crystals (CLEC) of laccase from Trametes versicolor with particular emphasis on the effect of pertinent variables and kinetic aspects of the reaction. The stability and antioxidant property of the conjugated product was improved as compared to the unconjugated tea polyphenols. The reaction was studied in 11 different solvents in order to deduce the solvent effect through an attempt to correlate the initial reaction rate with solvent properties such as hydrophobicity (logP), water solubility (logSw), electron pair acceptance (ETN) and donation abilities (DNN), polarisibility and dielectric constant which exhibit reasonable correlations. The study revealed, in general that polar solvents favour the initial reaction rate. The kinetics of the conjugation reaction conformed to the so-called Ping-Pong-Bi-Bi mechanism with catechin inhibition. The stability as well as activity of the CLEC was better than the free enzymes and immobilized laccase for practical application. In case of immobilized laccase system marginal diffusional limitation could be inferred from the experimental data. The kinetic parameters estimated by non-linear regression analysis were found to be KmPAA(mM) = 0.75, 1.8967 and Kmcat (mM) = 11.769, 15.1816 for free and immobilized laccase respectively. An attempt has been made to assess the activity of the laccase for the conjugation reaction in relation to other reactions such as dimerisation of ferulic acids and develop a protocol to enhance polyphenol antioxidant activity.

Keywords: laccase, catechin, conjugation reaction, antioxidant properties

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Authors: Djebbar Atmani, Aghiles Karim Aissat, Nadjet Debbache-Benaida, Nassima Chaher-Bazizi, Dina Atmani-Kilani, Meriem Rahmani-Berboucha, Naima Saidene, Malika Benloukil, Lila Azib

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Medicinal plants are believed to be an important source for the discovery of potential antioxidant, anti-inflammatory and anti-diabetic substances. The present study was designed to investigate the neuroprotective, anti-inflammatory, anti-diabetic and anti-hyperuricemic potential of Pistacia lentiscus, as well as the identification of active compounds. The antioxidant potential of plant extracts against known radicals was measured using various standard in vitro methods. Anti-inflammatory activity was determined using the paw edema model in mice and by measuring the secretion of the pro-inflammatory cytokine, whereas the anti-diabetic effect was assessed in vivo on streptozotocin-induced diabetic rats and in vitro by inhibition of alpha-amylase. The anti-hyperuricemic activity was evaluated using the xanthine oxidase assay, whereas neuroprotective activity was investigated using an Aluminum-induced toxicity test. Pistacia lentiscus extracts and fractions exhibited high scavenging capacity against DPPH, NO. and ABTS+ radicals in a dose-dependent manner and restored blood glucose levels, in vivo, to normal values, in agreement with the in vitro anti-diabetic effect. Oral administration of plant extracts significantly decreased carrageenan-induced mice paw oedema, similar to the standard drug, diclofenac, was effective in reducing IL-1β levels in cell culture and induced a significant increase in urinary volume in mice, associated to a promising anti-hyperuricemic activity. Plant extracts showed good neuroprotection and restoration of cognitive functions in mice. HPLC-MS and NMR analyses allowed the identification of known and new phenolic compounds that could be responsible for the observed activities. Therefore, Pistacia lentiscus could be beneficial in the treatment of inflammatory conditions and diabetes complications and the enhancement of cognitive functions.

Keywords: Pistacia lentiscus, anti-inflammatory, antidiabetic, flavanols, neuroprotective

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Authors: Aadila Cayenne, Hinrich Uellendahl

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Optimization of the anaerobic digestion (AD) process of halophytic plants is essential as the biomass contains a high salt content that can inhibit the AD process. Anaerobic co-digestion, together with manure, can resolve the inhibitory effects of saline biomass in order to dilute the salt concentration and establish favorable conditions for the microbial consortia of the AD process. The present laboratory study investigated the co-digestion of S. ramosissima (Sram), and pig manure (PM) in batch and semi-continuous stirred tank reactors (CSTR) under mesophilic (38oC) conditions. The 0.5L batch reactor experiments were in mono- and co-digestion of Sram: PM using different percent volatile solid (VS) based ratios (0:100, 15:85, 25:75, 35:65, 50:50, 100:0) with an inoculum to substate (I/R) ratio of 2. Two 5L CSTR systems (R1 and R2) were operated for 133 days with a feed of PM in a control reactor (R1) and with a co-digestion feed in an increasing Sram VS ratio of Sram: PM of 15:85, 25:75, 35:65 in reactor R2 at an organic loading rate (OLR) of 2 gVS/L/d and hydraulic retention time (HRT) of 20 days. After a start-up phase of 8 weeks for both reactors R1 and R2 with PM feed alone, the halophyte biomass Sram was added to the feed of R2 in an increasing ratio of 15 – 35 %VS Sram over an 11-week period. The process performance was monitored by pH, total solid (TS), VS, total nitrogen (TN), ammonium-nitrogen (NH4 – N), volatile fatty acids (VFA), and biomethane production. In the batch experiments, biomethane yields of 423, 418, 392, 365, 315, and 214 mL-CH4/gVS were achieved for mixtures of 0:100, 15:85, 25:75, 35:65, 50:50, 100:0 %VS Sram: PM, respectively. In the semi-continuous reactor processes, the average biomethane yields were 235, 387, and 365 mL-CH4/gVS for the phase of a co-digestion feed ratio in R2 of 15:85, 25:75, and 35:65 %VS Sram: PM, respectively. The methane yield of PM alone in R1 was in the corresponding phases on average 260, 388, and 446 mL-CH4/gVS. Accordingly, in the continuous AD process, the methane yield of the halophyte Sram was highest at 386 mL-CH4/gVS in the co-digestion ratio of 25:75%VS Sram: PM and significantly lower at 15:85 %VS Sram: PM (100 mL-CH4/gVS) and at 35:65 %VS Sram (214 mL-CH4/gVS). The co-digestion process showed no signs of inhibition at 2 – 4 g/L NH4 – N, 3.5 – 4.5 g/L TN, and total VFA of 0.45 – 2.6 g/L (based on Acetic, Propionic, Butyric and Valeric acid). This study demonstrates that a stable co-digestion process of S. ramosissima and pig manure can be achieved with a feed of 25%VS Sram at HRT of 20 d and OLR of 2 gVS/L/d.

Keywords: anaerobic co-digestion, biomethane production, halophytes, pig manure, salicornia ramosissima

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