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We present a magnetic activity study of GJ 436 using spectroscopic data from HARPS, spanning over 14 years, and additional data from NARVAL, falling within the HARPS observations. We study the CaII H&K, HeID3, NaI doublet, H$\alpha$ and CaII IRT triplets lines and explore linear correlations between them. Using the full HARPS dataset, we found indices H$\alpha$ vs CaII H&K & H$\alpha$ vs HeI to correlate positively. From the NARVAL dataset, covering one observing epoch, we found CaII IRT$_{3}$ vs CaII IRT$_{2}$ & CaII IRT$_{3}$ vs H$\alpha$ index to correlate negatively. We investigate long and short-term periodicity in these index variations using the Generalised Lomb-Scargle periodogram. For CaII H&K, NaI and H$\alpha$ indices, we detect long-term periods of 2470.7d (~ 6.8 years), 1861.6d (~ 5.1 years) and 2160.9d (~ 5.9 years) respectively, consistent with GJ 436's photometric cycle of ~ 7.4 years. Applying the "Pooled Variance" technique to H$\alpha$ & NaI indices, we found ~ 2500d to be the period of an activity cycle mechanism, in good agreement with the detected 2470.7d period. For CaII H&K and H$\alpha$ indices, we detect short-term periods of $39.47^{+0.11}_{-0.15}$d and $40.46^{+0.44}_{-0.52}$d respectively, identified as the stellar rotation period. The stellar rotation is detected after prewhitening the long-term periodicity. It is detected as well in the analysis of individual observing epochs., Comment: Accepted for publication in MNRAS. 13 pages, with additional online material

Freshwater is the main natural resource used for various forms of activities in our daily routines such as drinking, as well as for various developmental uses. Increasing the degree of contamination leads to disruption of our natural world which harms both the physical environments and the living organisms existing in the ecosystem. In the present paper, we studied water source samples taken from six spring water wells (Bas Cheliff Oued-Rhiou, Jdiouia, H'madna) located in rural areas of the Wilaya of Relizane, Algeria in the duration between January and December 2018. In accordance with the Algerian Bureau of Standards (IANOR) and the adopted World Health Organization (WHO), optimal guidelines for drinking water are tested, matched and validated for the characteristics of physical criteria and the bacterial load received. In addition, supplies of water have been tested for selected physical and chemical properties including temperature, acidity (pH), electrical conductivity (EC), ammonium, potassium, nitrate, phosphate, sulfate, copper concentration, and bacteriological well analyses for fecal bacillus contamination. The obtained results show that the mean parameter EC (526.25 μc/cm and 1293.92 μc/cm) was not substantially different because of the high concentration of total solids dissolved in water due to fertilizers dissolved used in agriculture. Insignificant variations of pH were found(6

Current communication candidly explicates the incremental aspect of generated entropy in apermeablesquare enclosure. Porosity aspects are mathematically formulated by Darcy-Forchheimer model, whereas the Lorentz force law is manifested to enclose magnetic field effectiveness. Water is capitalized as base fluid and nanoparticles composed of silver with different nanoparticles volume fractions are obliged. Thermal buoyancy is generated within the flow domain by provision of heat to left boundary. Description about physical modeling of the problem is manipulated in the form of PDEs with boundary constraints. Finite element procedure is used as a solution procedure to sort out the characteristics of flow problem. Variation in thermophysical attributes is presented through stream patterns, isothermal plots against flow contributing variables. Convective heat transfer through boundaries is measured through Nusselt number calculations.

Dengue virus (DENV) is a disease-causing agent normally transmitted from person to person through the bite of an infected mosquito. In addition to mosquito-borne cases of dengue, there are instances of transmission of dengue after receipt of blood products or donor organs or tissue. To improve blood safety, we developed a quantitative risk assessment model to estimate the dengue risk of transmission to blood transfusion recipients from preclinical and subclinical blood donors. We derived predictive coefficients from model simulations for predicting the risk outcomes such as monthly infectious blood units and transfusion-transmitted DENV cases based on the rate of reported clinical cases. The model was validated with a previous study where donor blood samples from the 2012 dengue transmission season in Rio de Janeiro, Brazil were tested for DENV RNA by a transcription-mediated amplification (TMA) assay. In that study, about 69·4% of donations were tested by the TMA assay and 78 samples were found positive, indicating that 112 DENV RNA-positive donations would have been detected if testing screening had been performed on all donations. Our model estimated a mean of 93 (2.5–97.5th%ile: 47–186) infected units among the donations, which was consistent with the reported numbers.

International audience; The French nuclear community is highly active in the field of earthquake engineering and more precisely, regarding seismic risk assessment. Among the existing safety-oriented frameworks, there is one which involves not only nuclear operators such as Electricité de France (EDF), the French Sustainable Energies and Atomic Energy Commission (CEA) and FRAMATOME, but also the French technical support organization which is the Institute for Radiological Protection and Nuclear Safety (IRSN). Within this framework, research activities are conducted, aiming to enhance knowledge in order to improve nuclear safety of either existing or new facilities. These activities deal with topics and challenging issues that appear to be significant in the seismic risk assessment process. More precisely, they aim to better assess the seismic margins when available, to better understand the beyond-design behavior of nuclear buildings or related equipment and to improve the necessary knowledge to produce robust seismic hazard assessment studies. The main objective of this paper is to give an overview of the past, ongoing, and future joint activities carried out by CEA-EDF-FRAMATOME-IRSN and will especially highlight main findings and future challenges and opportunities in the field of seismic safety of nuclear facilities. To reach the objective, technical focus will be made during the presentation.

FDA limited N-nitrosodimethylamine (NDMA) - a carcinogenic impurity formed during metformin (MET) tablets manufacturing - level to 96 ng/day; a step which led to recall of MET products. This work aims to investigate the root cause of NDMA formation during MET tablets manufacturing.We focused on three main contributing causes: use of water and heat during intra-granulation, and the nitrite/nitrate quantities in excipients. Thirteen MET tablet formulations (immediate or sustained-release) were manufactured, on batch level. Each batch was manufactured using one excipient and excluding one cause at a time and NDMA level was assayed.NDMA traces were undetectable in MET tablets manufactured using polyvinyl pyrrolidone or hydroxypropyl cellulose SSL, even when water and/or heat were employed during intra-granulation. Levels of NDMA in MET tablets with hydroxypropyl methyl cellulose (HPMC) E5 or carboxymethyl cellulose sodium 4000 were 67.08 ± 2.3 and 66.21 ± 2.5 ng/day, in the presence of water and/or heat. No impact of employing extra-granular PolyoxWater, heat, and excipients' nitrite and nitrate levels are the key players, which should collectively exist, to cause NDMA formation during MET tablets manufacturing.

Fatma Mohamed Elsenosy,1 Ghada Ahmed Abdelbary,2 Ahmed Hassen Elshafeey,2 Ibrahim Elsayed,2,3 Ahmed Roshdy Fares2 1Department of Clinical Pharmacy, Children’s Cancer Hospital, Cairo57357, Egypt; 2Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt; 3Department of Pharmaceutical Sciences, College of Pharmacy and Thumbay Research Institute for Precision Medicine, Gulf Medical University, Ajman, United Arab EmiratesCorrespondence: Ahmed Roshdy FaresDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Kasr El Aini Street, Cairo 11562, EgyptTel +20 12 88285866Email ahmed.roshdy@pharma.cu.edu.egPurpose: Duloxetine (DLX) is dual serotonin and norepinephrine reuptake inhibitor suffering from limited bioavailability (≈ 40%) due to extensive hepatic metabolism. This work aims to formulate and evaluate DLX intranasal thermoreversible cubosomal gels to enhance its bioavailability and ensure efficient brain targeting.Materials and Methods: Cubo-gels were prepared by 33 central composite design with three independent factors, lipid ratio (glycerol monooleate: glycerol tripalmitate), Pluronic F127%, and Pluronic F68%. The prepared formulations were evaluated for their particle size (PS), gelling temperature (GT), entrapment efficiency (EE%), and in vitro release. The cubo-gel with the highest desirability (0.88) was chosen as the optimized formulation. DLX cubo-gel was evaluated using differential scanning calorimetry, Fourier-transform infrared spectroscopy, X-ray powder diffraction, and transmission electron microscopy. Cytotoxicity study, ex vivo permeation study and in vivo bio-distribution study were conducted to evaluate the safety and efficacy of brain targeting.Results: The optimum cubo-gel was composed of 3.76 lipid ratio, 20% w/v PF127, and 5% w/v PF68. It had PS of 265.13 ± 9.85 nm, GT of 32 ± 0.05°C, EE% of 98.13 ± 0.50%, and showed controlled release behavior where 33% DLX was released within 6 hrs. The plain in situ cubo-gel had a significantly higher IC50 compared to DLX solution and DLX-loaded in situ cubo-gel. The ex vivo permeation study showed 1.27 enhancement in the drug permeation from DLX in situ cubo-gel. According to the in vivo bio-distribution study in plasma and brain, the intranasal DLX in situ cubo-gel showed a 1.96 fold improvement in brain bioavailability compared to the intranasal solution. Its BTE% and DTP% were 137.77 and 10.5, respectively, indicating efficient brain targeting after intranasal administration.Conclusion: Accordingly, intranasal DLX in situ cubo-gel can be considered as an innovative nano-carrier delivery system for bioavailability enhancement and efficient brain targeting of DLX to maximize its effect.Keywords: duloxetine, central composite design, cubosomes, thermoreversible in situ gel, intranasal, brain targeting

Today combination drugs are widely used to treat acute intestinal infections (AII). Acute intestinal infections requiring comprehensive treatment with antimicrobial drugs, enterosorbents, pro- and prebiotics and immune drugs. We have developed the composition and technology of drug wchich contain nifuroxazide and plant substance plantaglucid. This combination is a modern treatment of AII, because it combination has high efficiency, safety, availability and comfortable use.The purpose of the research was development of composition and technological scheme of the original combined drug in the form of capsules “Diaplant” for the complex treatment AII and the study of its pharmacoeconomic aspects.Results and discussion. The combination of nifuroxazide with plantaglucid, which has additional microbiological and pharmacological effects, was justified. To develop of the composition and technology this combined drug, the technology of separate preparation of masses for encapsulation with using excipients of different groups was used. The technological scheme of production of “Diaplant” capsules is developed and the specification for quality control of capsules is made. ATC/DDD-methodology showed that the cost for DDD of “Diaplant” was 14,54 UAH. The total cost of the average recommended daily doses of separate drugs (nifuroxazide and Plantaglucidum) ranged from 22,13 to 38,05 UAH. The use of “Diaplant” in clinical practice allows reducing the cost of pharmacotherapy of AII from 152 to 262 %.Conclusion. The technological scheme of production of the domestic drug in capsules “Diaplant” that contains nifuroxazide and Plantaglucidum was developed for pharmacotherapy of acute intestinal infections. The developed drug “Diaplant” has high antimicrobial, anti-inflammatory, antispasmodic and detoxic activity, normalizes intestinal motility and helps to restore the intestinal microflora.

This study aims at preparing electrospun PVA NFs incorporating simvastatin/chitosan nanoparticles (SIM CS NPs) as a controlled drug eluting scaffold for bone regeneration. Optimization was performed by Design Expert® software through establishing two factor, three level factorial design, where the independent variables were the applied voltage, flow rate and PVA solution/SIM CS NPs ratio. Formulation variables values for the optimized formula were 18KV, 0.5 mL/h, and 3:1 respectively. NFs diameter and mesh pore size were chosen as the dependent variables. The optimized NFs were evaluated morphologically, chemically, and physically. Additionally, in-vitro SIM release from the scaffolds was investigated along 24 days. Optimum NFs possessed 136 nm diameter size and 6.5 nm porosity. Also, they showed sustained SIM release for 24 days to achieve the desired goal in bone regeneration. The optimized NFs were implanted within induced bone defects in rabbits. In-vivo assessments were performed through cone beam computed tomography 3D images, bone density measurements, histological analysis and bone morphogenetic protein 2 (BMP 2) level. The obtained results proved the high potential of the optimized NFs in promoting bone regeneration compared to untreated group, non-medicated NFs group, free SIM group and NFs loaded with SIM group after 6 weeks of implantation.

Magnetic interactions between stars and close-in planets may lead to a detectable signal on the stellar disk. HD 189733 is one of the key exosystems thought to harbor magnetic interactions, which may have been detected in August 2013. We present a set of twelve wind models at that period, covering the possible coronal states and coronal topologies of HD 189733 at that time. We assess the power available for the magnetic interaction and predict its temporal modulation. By comparing the predicted signal with the observed signal, we find that some models could be compatible with an interpretation based on star-planet magnetic interactions. We also find that the observed signal can be explained only with a stretch-and-break interaction mechanism, while that the Alfv\'en wings scenario cannot deliver enough power. We finally demonstrate that the past observational cadence of HD 189733 leads to a detection rate of only between 12 to 23%, which could explain why star-planet interactions have been hard to detect in past campaigns. We conclude that the firm confirmation of their detection will require dedicated spectroscopic observations covering densely the orbital and rotation period, combined with scarcer spectropolarimetric observations to assess the concomitant large-scale magnetic topology of the star., Comment: 16 pages, 8 figures, 4 tables, accepted for publication in MNRAS

Curcumin or turmeric is the active constituent of Curcuma longa L. It has marvelous medicinal applications in many diseases. When the skin integrity is compromised due to either acute or chronic wounds, the body initiates several steps leading to tissue healing and skin barrier function restoration. Curcumin has very strong antibacterial and antifungal activities with powerful wound healing ability owing to its antioxidant activity. Nevertheless, its poor oral bioavailability, low water solubility and rapid metabolism limit its medical use. Tailoring suitable drug delivery systems for carrying curcumin improves its pharmaceutical and pharmacological effects. This review summarizes the most recent reported curcumin-loaded delivery systems for wound healing purposes, chiefly hydrogels, films, wafers, and sponges. In addition, curcumin nanoformulations such as nanohydrogels, nanoparticles and nanofibers are also presented, which offer better solubility, bioavailability, and sustained release to augment curcumin wound healing effects through stimulating the different healing phases by the aid of the small carrier.

Glaucoma is a chronic eye disease characterized by elevated intraocular pressure (IOP) which causes severe complications to the eyes and may lead to vision loss. The effective treatment of such diseases motivated the search for novel and unique drugs and delivery systems. It has been reported that, nifedipine (NF) is effective in reducing the elevated IOP due to vasodilatation of eye vascular smooth muscles. NF loaded thermo-sensitive in situ gels were prepared by the cold method using poloxamer 407 (P407) and hydroxypropyl methyl cellulose (HPMC) polymers adopting Box-Behnken experimental design. All the prepared formulae were tested for homogeneity, clarity, pH, isotonicity, gelling capacity, rheological behavior, in vitro drug release and were tested in vivo on rabbits. The prepared in situ gels were homogenous, transparent, having a pH ranged from 5 to 5.5 and undergo sol-gel transition within few seconds physiological temperature. The in situ gels showed sustained in vitro release of NF where about 76% of the loaded drug was released over 12 h. NF loaded in situ gels showed a 45.83 ± 2.91% reduction in the IOP, with no sign of toxicity or irritation to the eye in rabbits. The current investigations clarified the efficiency of this novel and unique NF loaded in situ gel for the control of the IOP compared to the conventional ophthalmic dosage forms.

In this work, sucrose acetate isobutyrate (SAIB) and polylactic co-glycolic acid (PLGA) were used alone or in combination as a matrix-former (MF) to prepare long-acting injectable rivastigmine (RV) in situ-forming microparticles (ISM). RV-ISM were prepared by the emulsification of an internal phase, containing the drug and the matrix former(s), into an external oily phase containing a stabilizer. The statistical design, Central Composite Design (CCD), was adopted as a quality by design (QbD) approach to optimize the formulation of RV-ISM systems. The fabricated RV-ISM systems was designed to minimize the initial burst drug release and maximize the sustainment of RV release from the ISM and ease of injection. The influence of critical formulation variables such as the matrix-former to drug (MF/D) ratio and SAIB to PLGA (S/P) ratio in the internal phase with respect to critical quality attributes (CQAs), such as the percentage drug release within the first day (Q1), the time required for 50% drug release (T50%) and the rate of injection, were studied using the CCD. The optimal RV-ISM system with the highest desirability value (0.74) was predicted to have an MF/D ratio of 11.7:1 (w/w) and an S/P ratio of 1.64:1 (w/w). The optimal RV-ISM system was assessed for its release profile, injectability, rheological properties, morphology, effect on cell viability, tolerance to γ-sterilization and in vivo performance in male albino rabbits. In vitro release studies revealed that the optimal RV-ISM system released 100% of its drug content throughout a release period of 30 days with only 15.5% drug release within the first day (Q1) and T50% of 13.09 days. Moreover, the optimal system showed a high injection rate of 1.012 mL/min, pseudoplastic flow, uniform spherical globules with homogenous particle size, minimal cytotoxicity and high tolerability to γ-sterilization. In vivo pharmacokinetic (PK) studies revealed that the rate of absorption of RV from the optimal RV-ISM system was controlled compared to a drug solution following either intramuscular (IM) or subcutaneous (SC) injection. Furthermore, the optimal RV-ISM was found to follow flip-flop PK with poor correlation between in vitro release and in vivo findings. These findings suggest that the optimal RV-ISM is a promising tool to achieve a sustained release therapy for RV; however, further investigation is still required to optimize the in vivo performance of RV-ISM.

Background: Intraarticular corticosteroid injection is an adjunct to core treatments for relief of moderate-to-severe pain in osteoarthritis (OA) patients. This randomized controlled trial was conducted to determine the effect of dexamethasone phonophoresis (DxPh) on knee OA. Patients and Methods: Forty six female patients with knee OA were randomized into two equal groups. The study group received DxPh over the medial side of the knee, transcutaneous electrical nerve stimulation (TENS), and quadriceps strengthening exercises. Control group received ultrasound therapy and the same TENS and exercise program. Pain was assessed using the visual analog scale (VAS) and the pain subscale of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pre- and posttreatment. Functional mobility was assessed by the Timed Up and Go (TUG) test, total WOMAC, and the joint stiffness and physical function subscales of WOMAC. The minimal clinically identifiable difference was used to calculate treatment effect sizes of both modalities, which was compared to intraarticular steroid injections. Results: The VAS, TUG, and WOMAC scores improved with both modalities. Pain intensity improved by 50.6%–58.0% in the study group (VAS and pain subscale of WOMAC, respectively) compared to 17.8%–28.6% for the control group. Functional mobility showed a higher rate of improvement in the DxPh group compared to control (37.7 vs. 17.5% for TUG and 53.2 vs. 23.0 and 56.1 vs. 26.4% for the joint stiffness and physical function subscales of WOMAC, respectively). Posttreatment results revealed statistically and clinically significant improvement in pain intensity and functional mobility in the DxPh group. Conclusion: DxPh resulted in a greater improvement in pain and function in patients with knee OA than therapeutic ultrasound combined with exercise and TENS. The effect size of phonophoresis was clinically significant and higher than that reported for intraarticular steroid injection from pooled data in the literature.

This study aims at preparing and optimizing lacidipine (LCDP) polymeric micelles using thin film hydration technique in order to overcome LCDP solubility-limited oral bioavailability. A two-factor three-level central composite face-centered design (CCFD) was employed to optimize the formulation variables to obtain LCDP polymeric micelles of high entrapment efficiency and small and uniform particle size (PS). Formulation variables were: Pluronic to drug ratio (A) and Pluronic P123 percentage (B). LCDP polymeric micelles were assessed for entrapment efficiency (EE%), PS and polydispersity index (PDI). The formula with the highest desirability (0.959) was chosen as the optimized formula. The values of the formulation variables (A and B) in the optimized polymeric micelles formula were 45% and 80%, respectively. Optimum LCDP polymeric micelles had entrapment efficiency of 99.23%, PS of 21.08 nm and PDI of 0.11. Optimum LCDP polymeric micelles formula was physically characterized using transmission electron microscopy. LCDP polymeric micelles showed saturation solubility approximately 450 times that of raw LCDP in addition to significantly enhanced dissolution rate. Bioavailability study of optimum LCDP polymeric micelles formula in rabbits revealed a 6.85-fold increase in LCDP bioavailability compared to LCDP oral suspension.

We developed the new сomplex drug diaplant in capsules for pharmacotherapy of acute intestinal infections. Diaplant consist of the nifuroxazide 200 mg and pantaglucidum 200 mg (leaf extract of Plantago major). Antiexudative activity of diaplant was established on the model of carrageenan edema. A comparative drug for the dynamics of antiexudative activity was sodium diclofenac in tablets («Novartis pharma», Sweden). As a result of the experiment, the maximum activity was on the third hour and was 43.1 % in diaplant, and was 64.4 % for sodium diclofenac. Spasmolytic activity of diaplant was studied by the method of «carbon labels». It has been found the identity of indicators for capsules diaplant with comparative drug plantaglucid (Zdorovye, Ukraine).

In this study the selection of in vivo predictive in vitro dissolution experimental set-ups using a multivariate analysis approach, in line with the Quality by Design (QbD) principles, is explored. The dissolution variables selected using a design of experiments (DoE) were the dissolution apparatus [USP1 apparatus (basket) and USP2 apparatus (paddle)], the rotational speed of the basket/or paddle, the operator conditions (dissolution apparatus brand and operator), the volume, the pH, and the ethanol content of the dissolution medium. The dissolution profiles of two nifedipine capsules (poorly soluble compound), under conditions mimicking the intake of the capsules with i. water, ii. orange juice and iii. an alcoholic drink (orange juice and ethanol) were analysed using multiple linear regression (MLR). Optimised dissolution set-ups, generated based on the mathematical model obtained via MLR, were used to build predicted in vitro-in vivo correlations (IVIVC). IVIVC could be achieved using physiologically relevant in vitro conditions mimicking the intake of the capsules with an alcoholic drink (orange juice and ethanol). The multivariate analysis revealed that the concentration of ethanol used in the in vitro dissolution experiments (47% v/v) can be lowered to less than 20% v/v, reflecting recently found physiological conditions.

International audience

The proposed solution addresses a security implementation for denial of service (DoS) attacks on software-defined networks (SDN) for which a combination of two technologies deployed on traditional networks that have been adapted to the SDN architecture is used. Implementing an intrusion prevention system (IPS) in an OpenFlow environment has emerged to enhance network security by analyzing data that travels through its structure and, together with this tool, the honeynet feature, executed through the command of an SDN controller. which orders packets identified as different from predefined transmission patterns to be forwarded to address a possible DoS attack.

The aim of this study was to incorporate methotrexate (MTX) into ultra-permeable niosomal vesicles, containing cremophor RH40 as an edge activator (EA) and polyvinyl alcohol (PVA) as a stabilizer to enhance the drug permeation. Formulae were prepared by ethanol injection method following a Box-Behnken design in order to optimize the formulation variables (EA%, stabilizer %, and sonication time). To investigate the role of both cremophor RH40 and PVA, conventional MTX niosomes and MTX niosomes containing PVA only were fabricated. Drug entrapment efficiency percent (EE%), particle size (PS) analysis, zeta potential (ZP) measurements, and transmission electron microscopy (TEM) were conducted to characterize the vesicles. Cell viability studies and ex vivo permeation experiments of the optimized formula were conducted. Lastly, in vivo skin deposition of MTX from both the optimized formula and MTX solution was performed in rats. Besides, histopathological changes in rat skin were assessed. The optimized MTX ultra-permeable niosomal formula demonstrated spherical morphology, with an EE% of 65.16% and a PS of 453.6 nm. The optimized formula showed better physical stability in comparison with that of the same composition but lacking PVA. The cell viability studies verified the superior cytotoxicity of the optimized formula, and the ex vivo permeation studies revealed its ability to improve the drug permeation. The optimized formula demonstrated a significant deposition of MTX in rat dorsal skin, and histopathological evaluation confirmed the tolerability of the optimized formula in rats upon topical application. Accordingly, ultra-permeable noisomes, as a stable nanosystem, could be promising for effective delivery of MTX.

This work consists of a description of the laminar flow of a nanoliquid in a trapezoidal cavity, In addition to measuring convective exchanges that take place there. The cavity in question is geometrically trapezoidal at right angles containing a hybrid Cu-Al2O3/Water nanofluid. The enclosure with the zigzagged wall is under the action of an external magnetic field and uniform at an angle of inclination γ. The Darcy-Forchheimer model has been used for the permeable domain. The impact due to Hartmann number (0 ≤ Ha ≤ 100), rotation speed (−4000 ≤ ω ≤ 4000), magnetic field inclination angle (0°≤γ ≤90°), Rayleigh number (103 ≤ Ra ≤ 105), cylinder radius (5 × 10−2 ≤ r ≤ 0.2), various N and volumetric fraction (0 ≤ ϕ ≤ 0.08) are investigated. Numerical results in Nusselt's number terms are validated with those in the literature. The obtained findings indicate that the flow of the nanofluid is strongly influenced through the application of a magnetic field, and the thermal performance of the cavity is improved with the augmentation of the Ra and Hartmann numbers. As well as the nanoparticles (NPs) improve heat transport, their rise in the volume fraction augments the total entropy generation with or without the application of the magnetic field and zigzags number (N). However, their contribution to improving heat transfer becomes less convincing with the rise in the Ha.

This study aims to formulate and optimize simvastatin loaded chitosan-tripolyphosphate nanoparticles (SIM CS-TPP NPs) using ionic gelation method to provide a local delivery system that controls and sustains the release of simvastatin in the desired dose to promote bone regeneration. Box-Behnken design was adopted for optimization of the formulation variables of the prepared nanoparticles namely, CS percentage, TPP percentage and homogenization time. The optimized formula was selected and characterized by transmission electronic microscopy, in-vitro release, swelling index and storage stability. The ability of the optimum formula to stimulate bone regeneration upon implantation in bone defect generated in rabbits was also evaluated. The optimum SIM CS-TPP NPs had particle size of 106 nm, zeta potential of 43.3 mv, polydispersity index of 0.295 and entrapment efficiency of 98.78% and also showed good storage stability over the first month in addition to controlled and steady release over 2 weeks that effectively delivered simvastatin in a therapeutic dose needed for bone regeneration. Cone beam computed tomography 3D images, bone density measurements and histopathological analysis confirmed the high potential of SIM CS-TPP NPs in promoting bone regeneration in the generated defects compared to both the non-medicated formula and untreated groups after 6 weeks of implantation.

The environmental assessment of the industrial effluents generated by the mineral fertilizer factory complex, Fertial (ARZEW), which discharges into the seacoast its liquid effluents loaded with organic and inorganic pollutants without adequate treatment [1] have revealed concentrations intense of suspended mater (SM). Wastewater treatment is a multi-step process to remove contaminants. In the first place, large solid particles are removed by sedimentation, flotation and filtration. In a second step, the biological treatment aggregates the smaller particles, forming so-called flocs. These flocs can be easily removed by sedimentation. This investigation investigates the separation of flocs from water in a circular secondary decanter. A mixing model is used to model the multiphase turbulent flow in the reservoir.

This work aims to prepare sustained release buccal mucoadhesive tablets of buspirone hydrochloride (BH) to improve its systemic bioavailability. The tablets were prepared according to 5×3 factorial design where polymer type was set at five levels (carbopol, hydroxypropyl methylcellulose, sodium alginate, sodium carboxymethyl cellulose and guar gum), and polymer to drug ratio at three levels (1:1, 2:1 and 3:1). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h) and time for release of 50% BH (T(₅₀%)) were chosen as dependent variables. Additional BH cup and core buccal tablets were prepared to optimize BH release profile and make it uni-directional along with the tablets mucoadhesion. Tablets were evaluated in terms of content uniformity, weight variation, thickness, diameter, hardness, friability, swelling index, surface pH, mucoadhesion strength and time and in vitro release. Cup and core formula (CA10) was able to adhere to the buccal mucosa for 8h, showed the highest Q8h (97.91%) and exhibited a zero order drug release profile. Pharmacokinetic study of formula CA10 in human volunteers revealed a 5.6 fold increase in BH bioavailability compared to the oral commercial Buspar® tablets. Conducting level A in vitro/in vivo correlation showed good correlation (r²=0.9805) between fractions dissolved in vitro and fractions absorbed in vivo.

The impact of hydrodynamics and media composition on nifedipine dissolution profile from IR (immediate release) soft capsules was investigated using dissolution apparatus USP1, USP2, USP3 and USP4 (United State Pharmacopoeia). Media composition was varied in terms of pH and content, to mimic the dosage form intake with water or non-alcoholic beverages (orange juice) and alcoholic beverages (orange juice/ethanol mixture (47% v/v)). Through construction of in vitro–in vivo correlations (IVIVC) with corresponding in vivo data from the literature, it was possible to evaluate the in vitro conditions that are likely to simulate the in vivo formulation behaviour. Both linear and nonlinear correlations were obtained depending on experimental set-ups. Testing of 20 mg nifedipine capsules in FaSSGFst (Fasted State Simulated Gastric Fluid pH 1.6; water administration) produced IVIVC with the USP3 (after time scaling) and USP4 apparatus. IVIVC were obtained for USP2, USP3 and USP4 in FaSSGFoj (Fasted State Simulated Gastric Fluid pH 3.4; orange juice administration). Linear and nonlinear correlations were obtained with the USP1, USP2 and USP3 apparatus when testing the capsules in FaSSGFoj/EtOH (orange juice/ethanol administration). This study highlighted that selection of physiologically relevant dissolution set-ups is critical for predicting the in vivo impact of formulations co-administration with water, non-alcoholic and alcoholic beverages.

This work aims to prepare sustained release buccal mucoadhesive lyophilized chitosan sponges of buspirone hydrochloride (BH) to improve its systemic bioavailability. Chitosan sponges were prepared using simple casting/freeze-drying technique according to 3(2) factorial design where chitosan grade was set at three levels (low, medium, and high molecular weight), and concentration of chitosan solution at three levels (0.5, 1, and 2%). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h), and time for release of 50% BH (T50%) were chosen as dependent variables. Additional BH cup and core buccal chitosan sponge were prepared to achieve uni-directional BH release toward the buccal mucosa. Sponges were evaluated in terms of drug content, surface pH, scanning electron microscopy, swelling index, mucoadhesion strength, ex vivo mucoadhesion time, and in vitro drug release. Cup and core sponge (HCH 0.5E) were able to adhere to the buccal mucosa for 8 h. It showed Q8h of 68.89% and exhibited a uni-directional drug release profile following Higuchi diffusion model.

The application of dispersion models in estimating the concentration levels of a solute, or a pollutant constituent, resulting from discharging waste into reservoirs and natural streams is presented. For the reservoir case, the mass balance principle of the aggregated dead zone (ADZ) model is employed, from which a general formulation for the dispersion of a pollutant constituent is derived. A hypothetical case is presented where an accidental spillage of a chemical discharge into a reservoir is considered. The prediction of the transient change in the concentration levels is analytically derived for the general case of reservoirs of arbitrary volumes and of various influx rates and duration. For the case of natural streams, the classic version of the Fickian diffusion model is modified, from which an expression for quantifying the coefficient of dispersion is proposed. The proposed dispersion model has been applied to a case study carried out on Waikato River, in New Zealand, where a dye is released in the river for the purpose of providing information about flushing rates at low steady flows. It has been demonstrated that the proposed dispersion model gives a more realistic estimation of the concentration profiles than those obtained from other existing models. Reasonably good comparisons were obtained with the measured concentration levels in the river at both the near-field and the far-field locations from the injection site.

The development of a quasi two-dimensional model for simulating the transverse and longitudinal energy gradient effects on the streamwise flow regime in meandering river channels is reported. The mathematical formulation of the curved flow is based on the principle of minimum stream power, where the total flow energy rate was divided into two components; longitudinal and transverse energy components. The mechanisms by which the energy is dissipated has been formulated on the basis of boundary resistance (longitudinal and transverse), internal turbulent friction and secondary circulation. The resulting increase of the lateral energy dissipation rate in the flow is emphasised. A direct relationship between the lateral energy dissipation rate and the ensuing excess boundary resistance to flow is proposed. The procedure used in the numerical calculations is described in detail. The model has been applied successfully to channels with rigid boundaries and found to give accurate predictions for the velocity and shear stress distributions. Finally, the model has been applied to two different case studies representing quasi river channel situations; a water supply canal and a curved channel with mobile bed. On the basis of the good comparisons obtained with measurements, it can be concluded that the model can be applied successfully to flow situations in river systems.

The development of a quasi two-dimensional computational model for simulating the transient variations of bed topography profiles in alluvial river channels is reported. The formulation of the model is based on combining the longitudinal flow momentum with the continuity principle of the sediment bed load. The Engelund-Hansen formula is employed in estimating the total sediment bed load along the reach of a river channel. The lateral bed load contribution from the total load is calculated in the same way as in calculating the lateral secondary currents from the main flow velocities. The numerical scheme and the computational procedure used in the study are described in detail. The simulated bed level profiles are verified through comparisons with experimental and field measurements taken from case studies in the literature for different flow conditions, channel characteristics, and sediment properties. The correlation between flow discharge, bed load, boundary friction, and channel slope is discussed. On the basis of the reasonably good comparisons with field data, it may be deduced that the model can be used for predicting the bottom topography variations in river channels.Key words: meandering rivers, bottom topography, sediment transport, bed load, boundary roughness, field measurements, experimental data, computational modelling, finite difference method.

The Stokes equation with the varying viscosity is considered in a thin tube structure, i.e. in a connected union of thin rectangles with heights of order $\varepsilon<, 22 pages, 20 figures

We study the nonsteady Stokes flow in a thin tube structure composed by two thin rectangles with lateral elastic boundaries which are connected by a domain with rigid boundaries. After a variational approach of the problem which gives us existence, uniqueness, regularity results, and somea prioriestimates, we construct an asymptotic solution. The existence of a junction region between the two rectangles imposes to consider, as part of the asymptotic solution, some boundary layer correctors that correspond to this region. We present and solve the problems for all the terms of the asymptotic expansion. For two different cases, we describe the order of steps of the algorithm of solving the problem and we construct the main term of the asymptotic expansion. By means of thea prioriestimates, we justify our asymptotic construction, by obtaining a small error between the exact and the asymptotic solutions.

The Stokes equation with the nonconstant viscosity is considered in a thin tube structure, i.e., in a connected union of thin rectangles with heights of order e ≪ 1 and bases of order 1 with smoothened boundary. An asymptotic expansion of the solution is constructed. In the case of random perturbations of the constant viscosity, we prove that the leading term for the velocity is deterministic, while for the pressure it is random, but the expectations of the pressure satisfies the deterministic Darcy equation. Estimates for the difference between the exact solution and its asymptotic approximation are proved. Bibliography: 11 titles. Illustrations: 3 figures.

The assignment of the absolute configuration of novel anti-inflammatory pyrrole derivatives has been accomplished by a combined strategy based on independent physical methods. The key step of our stereochemical characterization approach is the production at mg-scale of enantiomerically pure forms by HPLC on Chiralpak IA stationary phase.

Aims. We aim to investigate the long-term temporal evolution of the magnetic field of the solar-type star \xi Bootis A, both from direct magnetic field measurements and from the simultaneous estimate of indirect activity indicators. Methods. We obtained seven epochs of high-resolution, circularly-polarized spectra from the NARVAL spectropolarimeter between 2007 and 2011, for a total of 76 spectra. Using approximately 6,100 photospheric spectral lines covering the visible domain, we employed a cross-correlation procedure to compute a mean polarized line profile from each spectrum. The large-scale photospheric magnetic field of the star was then modelled by means of Zeeman-Doppler Imaging, allowing us to follow the year-to-year evolution of the reconstructed magnetic topology. Simultaneously, we monitored the width of several magnetically sensitive spectral lines, the radial velocity, the line asymmetry of intensity line profiles, and the chromospheric emission in the cores of the Ca II H and Halpha lines. Results. During the highest observed activity states, in 2007 and 2011, the large-scale field of \xi Boo A is almost completely axisymmetric and is dominated by its toroidal component. The magnetic topologies reconstructed for these activity maxima are very similar, suggesting a form of short cyclicity in the large-scale field distribution. Correlated temporal evolution, due to both rotational modulation and seasonal variability, is observed between the Ca II emission, the Halpha emission and the width of magnetically sensitive lines. When measurable, the differential rotation reveals a strong latitudinal shear in excess of 0.2 rad/d., Comment: 16 pages, 8 figures, accepted for publication in A&A, abstract shortened to respect the 1920 characters required

The effect of chronic cyanide exposure in the electroplating sections of three factories employing 36 workers was studied and compared with a control group. The concentration of cyanides to which the workers were exposed was measured. The regression line showing the relationship between thiocyanates in urine and the concentration of cyanides in the air was plotted. Increased percentages of haemoglobin and lymphocyte count were present in all exposed workers, in addition to punctate basophilia in 28 workers. Cyanmethaemoglobin was found to be characteristic. Apart from other complaints, two men with psychosis similar to one case reported in therapeutic thiocyanate intoxication were found. Twenty of the workers had thyroid enlargements to a variable degree and consistency, in two of whom it resembled lymphadenoid goitre. Thyroid 131I uptakes at 4 and 24 hours were significantly higher than in the controls, while 131PBI was unchanged. The reason for this iodine deficiency-like action is discussed.

A field survey in a village was carried out to study child health in a rural area. The vaccination scheme was found to be inadequate and the value of health education is stressed. Parasitic infestation was found to be higher than urban areas but significantly lower than 1959 and the latter is attributed to a safer water supply. Growth and development lagged behing the whole national standards particularly during the 1 - 6 years age period. Health care for the pre-school age, taking advantage of co-operation from medical faculties and local health authorities, is recommended.

One of the main problems encountered by the surgeon are visceral adhesions after abdominal surgery. This problem was studied in animal experiments by inducing peritoneal adhesions in 30 albino rats. The anti-inflammatory, resp. anti-adhesive effect of corticosteroids and antihistamines was tested by application of these drugs before, resp. after surgery. Anti-inflammatory proteolytic enzymes (Wobe-Mugos) were applied pre-, resp. postoperatively in two other groups. A fifth group served as controls. A modified cotton-pellet technique was used for the experiments. The best results were achieved when "Wobe-Mugos" was applied after surgery.