Search results for: Haifa Tounsi

Authors: Ayal Siegel, Moshe Inbar, Amatzya Peled

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This study examined the characteristic runoff coefficient in different urban areas. The main area studied is located in the city of Haifa, northern Israel. Haifa spreads out eastward from the Mediterranean seacoast to the top of the Carmel Mountain range with an elevation of 300 m. above sea level. For this research project, four watersheds were chosen, each characterizing a different part of the city; 1) Upper Hadar, a spacious suburb on the upper mountain side; 2) Qiryat Eliezer, a crowded suburb on a level plane of the watershed; 3) Technion, a large technical research university which is located halfway between the top of the mountain range and the coast line. 4) Keret, a remote suburb, on the southwestern outskirts of Haifa. In all of the watersheds found suitable, instruments were installed to continuously measure the water level flowing in the channels. Three rainfall gauges scattered in the study area complete the hydrological requirements for this research project. The runoff coefficient C in peak discharge events was determined by the Rational Formula. The main research finding is the significant relationship between the intensity of rainfall, and the impervious area which is connected to the drainage system of the watershed. For less intense rainfall, the full potential of the connected impervious area will not be exploited. As a result, the runoff coefficient value decreases as do the peak discharge rate and the runoff yield from the storm event. The research results will enable application to other areas by means of hydrological model to be be set up on GIS software that will make it possible to estimate the runoff coefficient of any given city watershed.

Keywords: runoff coefficient, rational method, time of concentration, connected impervious area.

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Authors: Hichem Sebai, Mohamed Amine Jabri, Kais Rtibi, Haifa Tounsi, Lamjed Marzouki

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Artemisia campestris has been widely used in Tunisian traditional medicine for its health beneficial effects. However, the present study aims at evaluating the antiulcer effects of Artemisia campestris aqueous extract (ACAE) as well as the mechanism of action involved in such gastroprotection. In this respect, male Wistar rats were divided into seven groups: control, aspirin (ASPR), ASPR + various doses of ACAE (100, 200 and 400 mg/kg, b.w.), ASPR+ famotidine and ASPR+ caffeic acid. Animals were pre-treated with ACAE extract during 10 days. We firstly showed that aspirin administration was accompanied by an oxidative stress status assessed by an increase of malondialdehyde (MDA) level, a decrease of sulfhydryl -(SH) groups content and depletion of antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Pre-treatment with ACAE protected against aspirin-induced gastric oxidative stress. More importantly, aspirin administration increased plasma and tissue hydrogen peroxide (H₂O₂), free iron and calcium levels while the ACAE pre-treatment reversed all aspirin-induced intracellular mediators disturbance. The results of the present study clearly indicated that AEAC gastroprotection might be related, at least in part, to its antioxidant properties as well as to various gastric mucosal defense mechanisms, including the protection of gastric sulfhydryls and an opposite effect on some intracellular mediators such as free iron, hydrogen peroxide, and calcium. However, our data confirm the use of Artemisia campestris extracts in the Tunisian traditional folk medicine for the treatment of gastrointestinal diseases.

Keywords: gastric ulcer, Artemisia campestris, oxidative stress, sulfhydryl groups, Fenton reaction, rat

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Authors: Hamid Merzouk, D. T. Talantikite, H. Haddad, Amel Tounsi

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ZnS is an important II-VI binary compound with large band-gap energy at room temperature. We present in this work preparation and characterization of ZnS and Cu doped ZnS thin films. The depositions are performed by a simple chemical bath deposition route. Structural properties are carried out by X-ray diffraction (XRD) and scanning electron microscopy (SEM). Optical transmittance is investigated by the UV-visible spectroscopy at room temperature.

Keywords: chemical, bath, method, Cu, doped, ZnS, thin, films

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Authors: Hamid Merzouk, Dajhida Talantikite, Amel Tounsi

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Thin films of ZnS have been deposited by chemical route into acidic medium. The deposition time fixed at 5 hours, and the bath temperature varied from 80° C to 95°C with an interval of 5°C. The X-ray diffraction (XRD), UV/ visible spectrophotometry, Fourier Transform Infrared spectroscopy (FTIR) have been used to study the effect of temperature on the structural and optical properties of ZnS thin films. The XRD spectrum of the ZnS layer obtained shows an increase of peaks intensity of ZnS with increasing bath temperature. The study of optical properties exhibit good transmittance (60–80% in the visible region), and the band gap energy of the ZnS thin film decrease from 3.71 eV to 3.64 eV while the refractive index (n) increase with increasing temperature bath. The FTIR analyze confirm our studies and show characteristics bands of vibration of Zn-S.

Keywords: ZnS thin films, XRD spectra, optical gap, XRD

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Authors: Merbouha Barka, K. H. Benrahou, A. Fakrar, A. Tounsi, E. A. Adda Bedia

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This paper presents an analytical investigation on the buckling and postbuckling behaviors of thick functionally graded plates subjected to thermal load .Material properties are assumed to be temperature dependent, and graded in the thickness direction according to a simple power law distribution in terms of the volume fractions of constituents. The formulations are based on first order shear deformation plate theory taking into account Von Karman nonlinearity and initial geometrical imperfection. By applying Galerkin method, closed-form relations of postbuckling equilibrium paths for simply supported plates are determined. Analysis is carried out to show the effects of material and geometrical properties, in-plane boundary restraint, and imperfection on the buckling and postbuckling loading capacity of the plates.

Keywords: functionally graded materials, postbuckling, first order shear deformation theory, imperfection

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Authors: S. Meguenni, A. Djahbar, K. Tounsi

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Electric railway traction systems are complex; they have electrical couplings, magnetic and solid mechanics. These couplings impose several constraints that complicate the modeling and analysis of these systems. An example of drive systems, which combine the advantages of the use of multiphase machines, power electronics and computing means, is mono convert isseur multi-machine system which can control a fully decoupled so many machines whose electric windings are connected in series. In this approach, our attention especially on modeling and independent control of two five phase synchronous machine with permanent magnet connected in series and fed by a matrix converter application to the rail traction (bogie of a locomotive BB 36000).

Keywords: synchronous machine, vector control Multi-machine/ Multi-inverter, matrix inverter, Railway traction

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Authors: Tayeb Bensattalah, Mohamed Zidour, Mohamed Ait Amar Meziane, Tahar Hassaine Daouadji, Abdelouahed Tounsi

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In this paper, the Differential Transform Method (DTM) is employed to predict and to analysis the non-local critical buckling loads of carbon nanotubes with various end conditions and the non-local Timoshenko beam described by single differential equation. The equation differential of buckling of the nanobeams is derived via a non-local theory and the solution for non-local critical buckling loads is finding by the DTM. The DTM is introduced briefly. It can easily be applied to linear or nonlinear problems and it reduces the size of computational work. Influence of boundary conditions, the chirality of carbon nanotube and aspect ratio on non-local critical buckling loads are studied and discussed. Effects of nonlocal parameter, ratios L/d, the chirality of single-walled carbon nanotube, as well as the boundary conditions on buckling of CNT are investigated.

Keywords: boundary conditions, buckling, non-local, differential transform method

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Authors: Sabrina Boutaleb, Fouad Bourad, Kouider Halim Benrahou, Abdelouahed Tounsi

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In the present work, the dynamic analysis of the functionally graded rectangular nanoplates is studied. The theory of nonlocal elasticity based on the quasi 3D high shear deformation theory (quasi 3D HSDT) has been employed to determine the natural frequencies of the nanosized FG plate. In HSDT, a cubic function is employed in terms of thickness coordinates to introduce the influence of transverse shear deformation and stretching thickness. The theory of nonlocal elasticity is utilized to examine the impact of the small scale on the natural frequency of the FG rectangular nanoplate. The equations of motion are deduced by implementing Hamilton’s principle. To demonstrate the accuracy of the proposed method, the calculated results in specific cases are compared and examined with available results in the literature, and a good agreement is observed. Finally, the influence of the various parameters, such as the nonlocal coefficient, the material indexes, the aspect ratio, and the thickness-to-length ratio, on the dynamic properties of the FG nanoplates is illustrated and discussed in detail.

Keywords: nonlocal elasticity theory, FG nanoplate, free vibration, refined theory, elastic foundation

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Authors: Sabrina Boutaleb, Kouider Halim Benrahou, François Schosseler, Abdelouahed Tounsi, El Abbas Adda Bedia

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The use of polyurethane in different areas becomes more frequent. This is due to significant advantages they have including their lightness and resistance. However, their use requires a mastery of their mechanical performance. We will present in this work, a COAPUR 6050 which can be used to develop composite materials. COAPUR 6050 is an associative polyurethane thickener allowing fine rheological adjustment of flat or semi-gloss paints. COAPUR 6050 is characterised by its thickening efficiency at low shear rate. It is a solvent-free liquid product. It promotes good paint pick up, while maintaining a low yield point after shearing, and consequently a good levelling. We will then determine its rheological behaviour experimentally using different annular gaps. The rheological properties of COAPUR 6050 were researched by rotational rheometer (Rheometer-Mars III) using different annular gaps. There is the influence of the size of the annular gap on the behaviour as well as on the rheological parameters of the COAPUR 6050. The rheological properties data of COAPUR 6050 were regressed by nonlinear regression method and their rheological models were established, are characterized by yield pseudoplastic model. In this case, it is essential to make a viscometric correction. The latter was developed and presented in the experimental results.

Keywords: COAPUR 6050, flow’s couette, polyurethane, rheological behaviours

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Authors: Redha Yeghnem, Laid Boulefrakh, Sid Ahmed Meftah, Abdelouahed Tounsi, El Abbas Adda Bedia

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In this study, the time-dependent behavior of damaged reinforced concrete shear wall structures strengthened with composite plates having variable fibers spacing was investigated to analyze their seismic response. In the analytical formulation, the adherent and the adhesive layers are all modeled as shear walls, using the mixed finite element method (FEM). The anisotropic damage model is adopted to describe the damage extent of the RC shear walls. The phenomenon of creep and shrinkage of concrete has been determined by Eurocode 2. Large earthquakes recorded in Algeria (El-Asnam and Boumerdes) have been tested to demonstrate the accuracy of the proposed method. Numerical results are obtained for non uniform distributions of carbon fibers in epoxy matrices. The effects of damage extent and the delay mechanism creep and shrinkage of concrete are highlighted. Prospects are being studied.

Keywords: RC shear wall structures, composite plates, creep and shrinkage, damaged reinforced concrete structures, finite element method

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Authors: Chirine Aouichaoui, Mohamed Tounsi, Ines Mrizak, Zouhair Tabka, Yassine Trabelsi

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The aim of this study was to provide percentile values for vertical jumping performances and anthropometric characteristics for athletic Tunisian children. One thousand and fifty-five athletic Tunisian children and adolescents (643 boys and 412 girls) aged 7-18 years were randomly selected to participate in our study. They were asked to perform squat jumps and countermovement jumps. For each measurement, a least square regression model with high order polynomials was fitted to predict mean and standard deviation of vertical jumping parameters and anthropometric variables. Smoothed percentile curves and percentile values for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles are presented for boys and girls. In conclusion, percentiles values of vertical jumping performances and anthropometric characteristics are provided. The new Tunisian reference charts obtained can be used as a screening tool to determine growth disorders and to estimate the proportion of adolescents with high or low muscular strength levels. This study may help in verifying the effectiveness of a specific training program and detecting highly talented athletes.

Keywords: percentile values, jump height, leg muscle power, athletes, anthropometry

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Authors: N. Boutaghane, F. Z. Tounsi

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Many physical and technological factors degrade the SPECT images, both qualitatively and quantitatively. For this, it is not always put into leading technological advances to improve the performance of tomographic gamma camera in terms of detection, collimation, reconstruction and correction of tomographic images methods. We have to master firstly the choice of various acquisition and reconstruction parameters, accessible to clinical cases and using the attenuation and scatter correction methods to always optimize quality image and minimized to the maximum dose received by the patient. In this work, an evaluation of qualitative and quantitative tomographic images is performed based on the acquisition parameters (counts per projection) and reconstruction parameters (filter type, associated cutoff frequency). In addition, methods for correcting physical effects such as attenuation and scatter degrading the image quality and preventing precise quantitative of the reconstructed slices are also presented. Two approaches of attenuation and scatter correction are implemented: the attenuation correction by CHANG method with a filtered back projection reconstruction algorithm and scatter correction by the subtraction JASZCZAK method. Our results are considered as such recommandation, which permits to determine the origin of the different artifacts observed both in quality control tests and in clinical images.

Keywords: attenuation, scatter, reconstruction filter, image quality, acquisition and reconstruction parameters, SPECT

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Authors: R. Bennai, H. Ait Atmane, Jr., A. Tounsi

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In this work, a new analytical approach using a refined theory of hyperbolic shear deformation of a beam was developed to study the free vibration of graduated sandwiches beams under different boundary conditions. The effects of transverse shear strains and the transverse normal deformation are considered. The constituent materials of the beam are supposed gradually variable depending the height direction based on a simple power distribution law in terms of the volume fractions of the constituents; the two materials with which we worked are metals and ceramics. The core layer is taken homogeneous and made of an isotropic material; while the banks layers consist of FGM materials with a homogeneous fraction compared to the middle layer. Movement equations are obtained by the energy minimization principle. Analytical solutions of free vibration and buckling are obtained for sandwich beams under different support conditions; these conditions are taken into account by incorporating new form functions. In the end, illustrative examples are presented to show the effects of changes in different parameters such as (material graduation, the stretching effect of the thickness, boundary conditions and thickness ratio - length) on the vibration free and buckling of an FGM sandwich beams.

Keywords: functionally graded sandwich beam, refined shear deformation theory, stretching effect, free vibration

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Authors: Yeghnem Redha, Guerroudj Hicham Zakaria, Hanifi Hachemi Amar Lemiya, Meftah Sid Ahmed, Tounsi Abdelouahed, Adda Bedia El Abbas

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Creep deformation of concrete is often responsible for excessive deflection at service loads which can compromise the performance of elements within a structure. Although laboratory test may be undertaken to determine the deformation properties of concrete, these are time-consuming, often expensive and generally not a practical option. Therefore, relatively simple empirically design code models are relied to predict the creep strain. This paper reviews the accuracy of creep and shrinkage predictions of reinforced concrete (RC) shear walls structures strengthened with carbon fibre reinforced polymer (CFRP) sheets, which is characterized by a widthwise varying fibre volume fraction. This review is yielded by CEB-FIB MC90 model. The time-dependent behavior was investigated to analyze their static behavior. In the numerical formulation, the adherents and the adhesives are all modelled as shear wall elements, using the mixed finite element method. Several tests were used to dem¬onstrate the accuracy and effectiveness of the proposed method. Numerical results from the present analysis are presented to illustrate the significance of the time-dependency of the lateral displacements.

Keywords: RC shear walls strengthened, CFRP sheets, creep and shrinkage, CEB-FIP MC90 model, finite element method, static behavior

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Authors: H. Sebai, M. A. Jabria, D. Wannes, H. Tounsi, L. Marzouki

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We aimed in the present study to investigate the protective effects of Tunisian Rosa canina aqueous extract (RCAE) against ethanol-induced gastric ulceration and oxidative stress in a rat model. In this respect, adult male Wistar rats were used and divided into six groups of ten each: control, EtOH, EtOH plus various doses of RCAE, EtOH plus famotidine and EtOH + gallic acid. Phytochemical and biochemical analysis were performed using colorimetric methods. We found that RCAE is rich in total polyphenols, total flavonoids, and condensed tannins, and exhibited an importance in vitro antioxidant activity on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. In vivo, the results showed that oral administration of EtOH caused macroscopic and histological changes in gastric mucosa. These injuries are accompanied by an oxidative stress status as assessed by an increase of lipid peroxidation as well as a decrease of antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Alcohol intoxication also induced intracellular mediators deregulation as assessed by an increase of hydrogen peroxide (H2O2), calcium and free iron levels in gastric mucosa. More, importantly, RCAE pretreatment reversed all macroscopic, histological and biochemical changes induced by EtOH administration. In conclusion, we suggest that RCAE has potent protective effects on acute ethanol-induced gastric ulceration related in part in part its antioxidant properties and its opposite effect on intracellular mediators. Indeed, Rosa canina can be offered as a food additive to protect against alcohol consumption-induced gastric and oxidative damage.

Keywords: alcohol, antioxidant properties, food additive, gastric ulceration, rat model, Rosa canina

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Authors: U. Harel, E. Carmeli

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The Purpose was to measure differences in activity patterns between major league adult and U-21 soccer players. Four U-21 players and four adult team players were evaluated using a repeated measures technique. All eight players were affiliated with the Maccabi Haifa soccer club from the Israeli professional and U-21major leagues, depending on the player’s age. GPS sensors were attached to the players during five consecutive games to identify patterns regarding running distance and speed according to the field positions. There was no significant difference in the total running distances covered by two age groups. When measuring running speed, an advantage was observed in the adult group when comparing two players from different age groups that played the same position. Differences in activity patterns were evident between adult and U-21 major league soccer players. Furthermore, differences in within group activity pattern emerged between the positions under investigation. These findings provide valuable knowledge that may serve the principle of training specificity.

Keywords: physical fitness, soccer, positional differences, GPS, training specificity

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Authors: Haifa Ben Saber, Mourad Elloumi

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In a number of domains, like in DNA microarray data analysis, we need to cluster simultaneously rows (genes) and columns (conditions) of a data matrix to identify groups of constant rows with a group of columns. This kind of clustering is called biclustering. Biclustering algorithms are extensively used in DNA microarray data analysis. More effective biclustering algorithms are highly desirable and needed. We introduce a new algorithm called, Enumerative tree (EnumTree) for biclustering of binary microarray data. is an algorithm adopting the approach of enumerating biclusters. This algorithm extracts all biclusters consistent good quality. The main idea of ​​EnumLat is the construction of a new tree structure to represent adequately different biclusters discovered during the process of enumeration. This algorithm adopts the strategy of all biclusters at a time. The performance of the proposed algorithm is assessed using both synthetic and real DNA micryarray data, our algorithm outperforms other biclustering algorithms for binary microarray data. Biclusters with different numbers of rows. Moreover, we test the biological significance using a gene annotation web tool to show that our proposed method is able to produce biologically relevent biclusters.

Keywords: DNA microarray, biclustering, gene expression data, tree, datamining.

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Authors: Haïfa Ben Mna, Ayed Added

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To evaluate the trace metals contamination status in the Gulf of Tunis, forty one sediment samples were analyzed using different approaches. According to certain contamination and ecological risk indices (Contamination Factor, Geoaccumulation index and Ecological risk index), Hg has the highest contamination level while pollution by Ni, Pb, Cd and Cr was absent. The highest concentrations of trace metals were found in sediments collected from the offshore and coastal areas located opposite the main exchange points with the gulf particularly, the Mejerda and Meliane Rivers, the Khalij Channel, Ghar El Melh and El Malah lagoons, Tunis Lake and Sebkhat Ariana. However, further ecological indices (Potential ecological risk index, Toxic unit and Mean effect-range median quotient) and comparison with sediment quality guidelines suggest that in addition to Mercury, Cr, Pb and Ni concentrations are detrimental to biota in both the offshore and areas near to the exchange points with the gulf. Moreover, in these areas the results from sequential extraction and individual contamination factor calculation pointed to the mobility and bioavailability of Cr, Pb and Ni.

Keywords: sediment, trace metals, contamination assessment, ecological risk, Tunis gulf

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Authors: Riam Abu-Much, Muhamad Hugerat

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Nanoscience has become one of the main science fields in the world; its importance is reflected in both society and industry; therefore, it is very important to intensify educational programs among teachers and students that aim to introduce "Nano Concepts" to them. Two different lab activities were developed for demonstrating the importance of nanoscale materials using unique points of view. In the first, electrical conductive films made of silver nanoparticles were fabricated. The silver nanoparticles were protected against aggregation using electrical conductive polypyrrole, which acts also as conductive bridge between them. The experiments show a simpler way for fabricating conductive thin film than the much more complicated and costly conventional method. In the second part, the participants could produce emulsions of liposome structures using Phosphatidylcholine as a surfactant, and following by minimizing the size of it from micro-scale to nanometer scale (400 nm), using simple apparatus called Mini-Extruder, in that way the participants could realize the change in solution transparency, and the effect of Tyndall when the size of the liposomes is reduced. Freshmen students from the Academic Arab College for Education in Haifa, Israel, who are studying to become science teachers, participated in this lab activity as part of the course "Chemistry in the Lab". These experiments are appropriate for teachers, high school and college students.

Keywords: case study, colloid, emulsion, liposome, surfactant

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Authors: Haifa El-Sadi, Maria Elektorowicz, Reed Rushing, Ammar Badawieh, Asif Chaudry

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Clay soils have particular properties that affect the assessment and remediation of contaminated sites. In clay soils, electro-kinetic transport of heavy metals has been carried out. The transport of these metals is predicated on maintaining a low pH throughout the cell, which, in turn, keeps the metals in the pore water phase where they are accessible to electro-kinetic transport. Supercritical fluid extraction and acid digestion were used for the analysis of heavy metals concentrations after the completion of electro-kinetic experimentation. Supercritical fluid (carbon dioxide) extraction is a new technique used to extract the heavy metal (lead, nickel, calcium and potassium) from clayey soil. The comparison between supercritical extraction and acid digestion of different metals was carried out. Supercritical fluid extraction, using ethylenediaminetetraacetic acid (EDTA) as a modifier, proved to be efficient and a safer technique than acid digestion technique in extracting metals from clayey soil. Mixing time of soil with EDTA before extracting heavy metals from clayey soil was investigated. The optimum and most practical shaking time for the extraction of lead, nickel, calcium and potassium was two hours.

Keywords: clay soil, heavy metals, supercritical fluid extraction, acid digestion

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Authors: Haifa Saleh, Kamiran Abduka, Robin Kalfat, Riadh Al-Mahaidi

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The effectiveness of using pre-stressing steel bars for shear strengthening of high strength reinforced concrete (RC) slabs was assessed. Two large-scale RC slabs were tested, one without shear reinforcement and the second strengthened against punching shear failure using pre-stressing steel bars. The two slabs had the same dimensions, flexural reinforcement ratio, loading and support arrangements. The experimental program including the method of strengthening, set up and instrumentation are described in this paper. The experimental results are analyzed and discussed in terms of the structural behavior of the RC slabs, the performance of pre-stressing steel bolts and failure modes. The results confirmed that the shear strengthening technique increased the shear capacity, ductility and yield capacity of the slab by up to 15%, 44%, and 22%, respectively compared to the unstrengthened slab. The strengthening technique also successfully contributed to changing the failure mode from a brittle punching shear mode to ductile flexural failure mode. Vic3D digital image correlation system (photogrammetry) was also used in this research. This technique holds several advantages over traditional contact instrumentations including that it is inexpensive, it produces results that are simple to analyze and it is remote visualization technique. The displacement profile along the span of the slab and rotation has been found and compared with the results obtained from traditional sensors. The performance of the photogrammetry technique was very good and the results of both measurements were in very close agreement.

Keywords: flat slab, photogrammetry, punching shear, strengthening

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Authors: Ada Yurman

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Social reactions to deviant groups with political goals follow two central patterns; one that associates personal characteristics with deviant behavior, and the other that claims that society is to be blamed for deviant behavior. The establishment usually tends towards the former notion and thus disclaims any responsibility for the distress of the underprivileged, while it is usually those who oppose government policies who believe that the fault lies with society. The purpose of the present research was to examine social reactions to the Wadi Salib riots that occurred in Haifa in 1959. These riots represented the first ethnic protest within Israeli society with its ideology of the ingathering of the exiles. The central question was whether this ideology contributed to the development of a different reaction when compared to reactions to similar events abroad. This question was examined by means of analyzing articles in the Israeli press of that period. The Israeli press representing the views of the establishment was at pains to point out that the rioters were criminals, their object being to obstruct the development of society. Opposition party leaders claimed that the rioters lived in poor circumstances, which constituted a direct result of government policies. An analysis of press reports on the Wadi Salib riots indicates a correspondence between the reaction to these events and similar events abroad. Nevertheless, the reaction to the Wadi Salib riots did not only express a conflict between different political camps, but also different symbolic universes. Each group exploited the events at Wadi Salib to prove that their ideology was the legitimate one.

Keywords: riots, media, political deviance, symbolic universe

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Authors: Yael Shai, Dror L. Angel, Dror Zurel, Peleg Astrahan, Maxim Rubin-Blum, Eyal Rahav

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The high demand for oil and its by-products is symptomatic of the 21st century and occasionally leads to oil spills and pollution of coastal waters. Marine oil pollution may originate from a variety of sources -urban runoff, tanker cleaning, drilling activities, and oil spills. These events may release large amounts of highly toxic polycyclic aromatic hydrocarbons (PAHs) and other pollutants to coastal water, thereby threatening local marine life. Here, we investigated the effects of crude oil on the temporal dynamics of phytoplankton and heterotrophic bacteria in Israeli coastal waters. To this end, we added crude oil (500 µm thick layer, with and without additional nutrients; NO₃ and PO₄) to mesocosms (1m³ bags) containing oligotrophic surface coastal water collected near Haifa during summer and winter. Changes in phytoplankton biomass, activity and diversity were monitored daily for 5-6 days. Our results demonstrate that crude oil addition resulted in a pronounced decrease in phytoplankton biomass and production rates, while heterotrophic bacterial production increased significantly. Importantly, a few days post addition we found that the oil-degrading bacteria, Oleibacter sp. and Oleispira sp. appeared in the mesocosms and that the addition of nutrients (along with the crude oil) further increased this trend. This suggests that oil-degrading bacteria may be NO₃ and PO₄ limited in Israeli coastal waters. The results of this study should enable us to establish improved science-based environmental policy with respect to handling crude oil pollution in this region.

Keywords: heterotrophic bacteria, nutrients, mesocosm, oil pollution, oligotrophic, phytoplankton

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Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

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Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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