Search results for: protein design

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: Narjis Zehra

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After automobile revolution 1.0, we have automobile revolution 2.0 standing at the horizon, Autonomous Vehicles (AVs). While the technology is developing into more adaptable form, the conversations around its impact on our cities have already started on multiple scales, from academic institutions and community town halls, to the offices of mayors. In order to explore more the AVs impact on Urban transformation, we first inquire if cities can be redesigned or rebuilt. Secondly, we discuss expectation management for the public and policy in terms of what people think/believe AV technology will deliver, and what the current technological evidence suggests the technology and its adoption will look like. Thirdly, based on these discussions, we take Pittsburgh, PA, as a case study to extrapolate what other cities might need to do in order to prepare themselves for the upcoming technological revolution, that may impact more than just the research institutes. Finally, we conclude by suggesting a political way forward to embed urban design with AV technology for equitable cities of tomorrow.

Keywords: urban design, autonomous vehicles, transformation, policy

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Authors: Irena Kostovska, Katerina Tosheska Trajkovska, Svetlana Cekovska, Julijana Brezovska Kavrakova, Hristina Ampova, Sonja Topuzovska, Ognen Kostovski, Goce Spasovski, Danica Labudovic

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Background: Proteinuria is an important feature of secondary nephropathies. The quantitative and qualitative analysis of proteinuria plays an important role in determining the types of proteinuria (glomerular, tubular and mixed), in the diagnosis and prognosis of secondary nephropathies. The damage of the glomerular basement membrane is responsible for a proteinuria characterized by the presence of large amounts of protein with high molecular weights such as albumin (69 kilo Daltons-kD), transferrin (78 kD) and immunoglobulin G (150 kD). An insufficiency of proximal tubular function is the cause of a proteinuria characterized by the presence of proteins with low molecular weight (LMW), such as retinol binding protein (21 kD) and α1-microglobulin (31 kD). In some renal diseases, a mixed glomerular and tubular proteinuria is frequently seen. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) is the most widely used method of analyzing urine proteins for clinical purposes. The main aim of the study is to determine the type of proteinuria in the most common secondary nephropathies such as diabetic, hypertensive nephropathy and preeclampsia. Material and methods: In this study were included 90 subjects: subjects with diabetic nephropathy (n=30), subjects with hypertensive nephropahty (n=30) and pregnant women with preeclampsia (n=30). We divided all subjects according to UM/CR into three subgroups: macroalbuminuric (UM/CR >300 mg/g), microalbuminuric (UM/CR 30-300 mg/g) and normolabuminuric (UM/CR<30 mg/g). In all subjects, we measured microalbumin and creatinine in urine with standard biochemical methods. Separation of urinary proteins was performed by SDS-PAGE, in several stages: linear gel preparation (4-22%), treatment of urinary samples before their application on the gel, electrophoresis, gel fixation, coloring with Coomassie blue, and identification of the separated protein fractions based on standards with exactly known molecular weight. Results: According to urinary microalbumin/creatinin ratio in group of subject with diabetic nephropathy, nine patients were macroalbuminuric, while 21 subject were microalbuminuric. In group of subjects with hypertensive nephropathy, we found macroalbuminuria (n=4), microalbuminuria (n=20) and normoalbuminuria (n=6). All pregnant women with preeclampsia were macroalbuminuric. Electrophoretic separation of urinary proteins showed that in macroalbuminric patients with diabetic nephropathy 56% have mixed proteinuria, 22% have glomerular proteinuria and 22% have tubular proteinuria. In subgroup of subjects with diabetic nephropathy and microalbuminuria, 52% have glomerular proteinuria, 8% have tubular proteinuria, and 40% of subjects have normal electrophoretic findings. All patients with maroalbuminuria and hypertensive nephropathy have mixed proteinuria. In subgroup of patients with microalbuminuria and hypertensive nephropathy, we found: 32% with mixed proteinuria, 27% with normal findings, 23% with tubular, and 18% with glomerular proteinuria. In all normoalbuminruic patiens with hypertensive nephropathy, we detected normal electrophoretic findings. In group of subjects pregnant women with preeclampsia, we found: 81% with mixed proteinuria, 13% with glomerular, and 8% with tubular proteinuria. Conclusion: By SDS PAGE method, we detected that in patients with secondary nephropathies the most common type of proteinuria is mixed proteinuria, indicating both loss of glomerular permeability and tubular function. We can conclude that SDS PAGE is high sensitive method for detection of renal impairment in patients with secondary nephropathies.

Keywords: diabetic nephropathy, preeclampsia, hypertensive nephropathy, SDS PAGE

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Authors: Ahmad Idris, Armaya`u Suleiman Labo, Ado Yusuf Abdulfatah, Murtala Umar

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Super pave is the short form of Superior Performing Asphalt Pavement and represents a basis for specifying component materials, asphalt mixture design and analysis, and pavement performance prediction. This new technology is the result of long research projects conducted by the strategic Highway Research program (SHRP) of the Federal Highway Administration. This research was aimed at examining the suitability of Aggregates found in Kano for used in super pave design method. Aggregates samples were collected from different sources in Kano Nigeria and their Engineering properties, as they relate to the SUPERPAVE design requirements were determined. The average result of Coarse Aggregate Angularity in Kano was found to be 87% and 86% of one fractured face and two or more fractured faces respectively with a standard of 80% and 85% respectively. Fine Aggregate Angularity average result was found to be 47% with a requirement of 45% minimum. A flat and elongated particle which was found to be 10% has a maximum criterion of 10%. Sand equivalent was found to be 51% with the criteria of 45% minimum. Strength tests were also carried out, and the results reflect the requirements of the standards. The tests include Impact value test, Aggregate crushing value and Aggregate Abrasion tests and the results are 27.5%, 26.7% and 13% respectively with a maximum criteria of 30%. Specific gravity was also carried out and the result was found to have an average value of 2.52 with a criterion of 2.6 to 2.9 and Water absorption was found to be 1.41% with maximum criteria of 0.6%. From the study, the result of the tests indicated that the aggregates properties have met the requirements of Super pave design method based on the specifications of ASTMD 5821, ASTM D 4791, AASHTO T176, AASHTO T33 and BS815.

Keywords: aggregates, construction, road design, super pave

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Authors: Ryadi Adityavarman

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The study is an analysis by using the postcolonial theoretical lens on the search for a distinctive architectural identity by architect Maclaine Pont in Indonesia in the early twentieth century. Influenced by progressive architectural thinking and enlightened humanism at the time, Pont applied the fundamental principles of Structural Rationalism by using a creative combination of traditional Indonesian architectural typology and innovative structural application. The interpretive design strategy also celebrated creative use of local building materials with sensible tropical climate design response. Moreover, his holistic architectural scheme, including inclusion of local custom of building construction, represents the notion of Gesamkunstwerk. By using such hybrid strategy, Maclaine Pont intended to preserve the essential cultural identity and vernacular architecture of the indigenous. The study will chronologically investigate the evolution of Structural Rationalism architecture philosophy of Viollet-le-Duc to Hendrik Berlage’s influential design thinking in the Dutch modern architecture, and subsequently to the Maclaine Pont’s innovative design in Indonesia. Consequently, the morphology analysis on his exemplary design works of ITB campus (1923) and Pohsarang Church (1936) is to understand the evolutionary influence of Structural Rationalism theory. The postmodern analysis method is to highlight the validity of Pont’s idea in the contemporary Indonesian architecture within the culture of globalism era.

Keywords: Indonesian modern architecture, postcolonial, structural rationalism, critical regionalism

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Authors: Nonhlanhla Nkosi, Kulsum Kondiah

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The toxicological manifestation of heavy metals motivates interest towards the development of a reliable, eco-friendly biosorption process. With that being said, the aim of the current study was to characterise the EPS from heavy-metal resistant bacteria isolated from acid mine decant on the West Rand, Gauteng, South Africa. To achieve this, six exopolysaccharide (EPS) producing, metal resistant strains (Pb101, Pb102, Pb103, Pb204, Co101, and Ni101) were identified as Bacillus safensis strain NBRC 100820, Bacillus proteolyticus, Micrococcus luteus, Enterobacter sp. Pb204, Bacillus wiedmannii and Bacillus zhangzhouensis, respectively with 16S rRNA sequencing. Thereafter, EPS was extracted using chemical (formaldehyde/NaOH) and physical (ultrasonification) methods followed by physicochemical characterisation of carbohydrate, DNA, and protein contents using chemical assays and spectroscopy (FTIR- Fourier transformed infrared and 3DEEM- three-dimensional excitation-emission matrix fluorescence spectroscopy). EPS treated with formaldehyde/NaOH showed better recovery of macromolecules than ultrasonification. The results of the present study showed that carbohydrates were more abundant than proteins, with carbohydrate and protein concentrations of 8.00 mg/ml and 0.22 mg/ml using chemical method in contrast to 5.00 mg/ml and 0.77 mg/ml using physical method, respectively. The FTIR spectroscopy results revealed that the extracted EPS contained hydroxyl, amide, acyl, and carboxyl groups that corresponded to the aforementioned chemical analysis results, thus asserting the presence of carbohydrates, DNA, polysaccharides, and proteins in the EPS. These findings suggest that identified functional groups of EPS form surface charges, which serve as the binding sites for suspended particles, thus possibly mediating adsorption of divalent cations and heavy metals. Using the extracted EPS in the development of a cost-effective biosorption solution for industrial wastewater treatment is attainable.

Keywords: biosorbent, exopolysaccharides, heavy metals, wastewater treatment

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Authors: Mareli Hattingh, I. Jaco Van der Walt, Frans B. Waanders

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A waste-to-energy plasma system was designed by Necsa for commercial use to create electricity from unsorted municipal waste. Fly ash particles must be removed from the syngas stream at operating temperatures of 1000 °C and recycled back into the reactor for complete combustion. A 2D2D high efficiency cyclone separator was chosen for this purpose. During this study, two cyclone design methods were explored: The Classic Empirical Method (smaller cyclone) and the Flow Characteristics Method (larger cyclone). These designs were optimized with regard to efficiency, so as to remove at minimum 90% of the fly ash particles of average size 10 μm by 50 μm. Wood was used as feed source at a concentration of 20 g/m³ syngas. The two designs were then compared at room temperature, using Perspex test units and three feed gases of different densities, namely nitrogen, helium and air. System conditions were imitated by adapting the gas feed velocity and particle load for each gas respectively. Helium, the least dense of the three gases, would simulate higher temperatures, whereas air, the densest gas, simulates a lower temperature. The average cyclone efficiencies ranged between 94.96% and 98.37%, reaching up to 99.89% in individual runs. The lowest efficiency attained was 94.00%. Furthermore, the design of the smaller cyclone proved to be more robust, while the larger cyclone demonstrated a stronger correlation between its separation efficiency and the feed temperatures. The larger cyclone can be assumed to achieve slightly higher efficiencies at elevated temperatures. However, both design methods led to good designs. At room temperature, the difference in efficiency between the two cyclones was almost negligible. At higher temperatures, however, these general tendencies are expected to be amplified so that the difference between the two design methods will become more obvious. Though the design specifications were met for both designs, the smaller cyclone is recommended as default particle separator for the plasma system due to its robust nature.

Keywords: Cyclone, design, plasma, renewable energy, solid separation, waste processing

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Authors: Daniel Aberdam

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Haploinsufficiency of PAX6 in humans is the main cause of congenital aniridia, a rare eye disease characterized by reduced visual acuity. Patients have also progressive disorders including cataract, glaucoma and corneal abnormalities making their condition very challenging to manage. Aniridia-related keratopathy (ARK), caused by a combination of factors including limbal stem-cell deficiency, impaired healing response, abnormal differentiation, and infiltration of conjunctival cells onto the corneal surface, affects up to 95% of patients. It usually begins in the first decade of life resulting in recurrent corneal erosions, sub-epithelial fibrosis with corneal decompensation and opacification. Unfortunately, current treatment options for aniridia patients are currently limited. Although animal models partially recapitulate this disease, there is no in vitro cellular model of AKT needed for drug/therapeutic tools screening and validation. We used genome editing (CRISPR/Cas9 technology) to introduce a nonsense mutation found in patients into one allele of the PAX6 gene into limbal stem cells. Resulting mutated clones, expressing half of the amount of PAX6 protein and thus representative of haploinsufficiency were further characterized. Sequencing analysis showed that no off-target mutations were induced. The mutated cells displayed reduced cell proliferation and cell migration but enhanced cell adhesion. Known PAX6 targets expression was also reduced. Remarkably, addition of soluble recombinant PAX6 protein into the culture medium was sufficient to activate endogenous PAX6 gene and, as a consequence, rescue the phenotype. It strongly suggests that our in vitro model recapitulates well the epithelial defect and becomes a powerful tool to identify drugs that could rescue the corneal defect in patients. Furthermore, we demonstrate that the homeotic transcription factor Pax6 is able to be uptake naturally by recipient cells to function into the nucleus.

Keywords: Pax6, crispr/cas9, limbal stem cells, aniridia, gene therapy

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Authors: Kalyan Deepak Kolla, Ketan Paua, Rajkumar Bhagate

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Transmission dynamics occupy major role in customer perception of the product in both senses of touch and quality of sound. The quantity and quality of sound perceived is more concerned with the whine noise of the gears engaged. Whine noise is tonal in nature and tonal noises cause fatigue and irritation to customers, which in turn affect the quality of the product. Transmission error is the usual suspect for whine noise, which can be caused due to misalignments, tolerances, manufacturing variabilities. In-cabin noise is also more sensitive to the gear design. As the details of the gear tooth design and manufacturing are in microns, anything out of the tolerance zone, either in design or manufacturing, will cause a whine noise. This will also cause high variation in stress and deformation due to change in the load and leads to the fatigue failure of the gears. Hence gear design and development take priority in the transmission development process. This paper aims to study such variability by considering five pairs of helical spur gears and their effect on the transmission error, contact pattern and vibration level on the transmission.

Keywords: gears, whine noise, manufacturing variability, mount vibration variability

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Authors: Valery A. Aurov, Maria D. Bausheva, Elena V. Uliyanova

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The problems of sustainability of contemporary high-rise buildings now demand an altogether new approach, which corresponds with the laws of dialectics. We should imply the principle “going from mega-object to the so called mezzo-object.” So the scientists have arrived at the conclusion that a contemporary “skyscraper” must not increase in height but develop horizontal space axes which unite a complex of high-rise buildings into a single composition. This is necessary both for safety issues and increasing skyscrapers’ functioning qualities. As a result, architects single out a quality unit in a dominating group of high-rise constructions and make a conclusion about the influence of visual fields on the designing parameters of this group.

Keywords: design, high-rise buildings, skyscrapers, sustainability, visual fields, dominating group, regulations, design recommendations

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Authors: Parul Kulshreshtha, Subrata Sinha, Rakesh Bhatnagar

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This study was conducted by taking B. anthracis as a model pathogen. On infecting a host, B. anthracis secretes three proteins, namely, protective antigen (PA, 83kDa), edema factor (EF, 89 kDa) and lethal factor (LF, 90 kDa). These three proteins are the components of two anthrax toxins. PA binds to the cell surface receptors, namely, tumor endothelial marker (TEM) 8 and capillary morphogenesis protein (CMG) 2. TEM8 and CMG2 interact with LDL-receptor related protein (LRP) 6 for endocytosis of EF and LF. On entering the cell, EF acts as a calmodulin-dependent adenylate cyclase that causes a prolonged increase of cytosolic cyclic adenosine monophosphate (cAMP). LF is a metalloprotease that cleaves most isoforms of mitogen-activated protein kinase kinases (MAPKK/MEK) close to their N-terminus. By secreting these two toxins, B.anthracis ascertains death of the host. Once the systemic levels of the toxins rise, antibiotics alone cannot save the host. Therefore, toxin-specific inhibitors have to be developed. In this wake, monoclonal antibodies have been developed for the neutralization of toxic effects of anthrax toxins. We created hybridomas by using spleen of mice that were actively immunized with rLFn (recombinant N-terminal domain of lethal factor of B. anthracis) to obtain anti-toxin antibodies. Later on, separate group of mice were immunized with rLFn to obtain a polyclonal control for passive immunization studies of monoclonal antibodies. This led to the identification of one cohort of rLFn-immunized mice that harboured disease-enhancing polyclonal antibodies. At the same time, the monoclonal antibodies from all the hybridomas were being tested. Two hybridomas secreted monoclonal antibodies (H8 and H10) that were cross-reactive with EF (edema factor) and LF (lethal factor), while the other two hybridomas secreted LF-specific antibodies (H7 and H11). The protective efficacy of H7, H8, H10 and H11 was investigated. H7, H8 and H10 were found to be protective. H11 was found to have disease enhancing characteristics in-vitro and in mouse model of challenge with B. anthracis. In this study the disease enhancing character of H11 monoclonal antibody and anti-rLFn polyclonal sera was investigated. Combination of H11 with protective monoclonal antibodies (H8 and H10) reduced its disease enhancing nature both in-vitro and in-vivo. But combination of H11 with LETscFv (an scFv with VH and VL identical to H10 but lacking Fc region) could not abrogate the disease-enhancing character of H11 mAb. Therefore it was concluded that for suppression of disease enhancement, Fc portion was absolutely essential for interaction of H10 with H11. Our study indicates that the protective potential of an antibody depends equally on its idiotype/ antigen specificity and its isotype. A number of monoclonal and engineered antibodies are being explored as immunotherapeutics but it is absolutely essential to characterize each one for their individual and combined protective potential. Although new in the sphere of toxin-based diseases, it is extremely important to characterize the disease-enhancing nature of polyclonal as well as monoclonal antibodies. This is because several anti-viral therapeutics and vaccines have failed in the face of this phenomenon. The passive –immunotherapy thus needs to be well formulated to avoid any contraindications.

Keywords: immunotherapy, polyclonal, monoclonal, antibody-dependent disease enhancement

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Authors: Dalia Atallah, Lamiaa Ahmed, Hala Zaki, Mahmoud Khattab

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Background: Isoprenaline (ISO) administration induces myocardial damage via oxidative stress and endothelial dysfunction. Atorvastatin (ATV) treatment improves both oxidative stress and endothelial dysfunction yet recent studies have reported a pro-oxidant effect upon ATV administration on both clinical and experimental studies. The present study was directed to investigate the effect of ATV pre-treatment and treatment on ISO-induced myocardial damage. Methods: Male rats were divided into five groups (n = 10). Rats were given ISO (5mg/kg/day, i.p.) for one week with or without ATV (10mg/kg/day, p.o.). ATV was given either as pre-treatment for one week before its co-administration with ISO for another week or as a treatment for two weeks at the end of the ISO administration. At the end of the experiment, the electrocardiographic examination was done and blood was isolated for the estimation of plasma creatine kinase MB (CK-MB) activity. Rats were then sacrificed and the whole ventricles were isolated for histological examination and the estimation of lipid peroxides as malondialdehyde (MDA) level, reduced glutathione (GSH) level, catalase activity, total nitrate-nitrite (NOx), as well as the estimation of both endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) protein expression. Results: ISO-induced myocardial damage showed a significant elevation in ST segment, an increase in CK-MB activity, as well as increased oxidative stress biomarkers. Also, ISO-treated rats showed a significant decrease in myocardial NOx level and eNOS as well as degeneration in the myocardium. ATV pre-treatment didn’t show any protection to ISO-treated rats. On the other hand, ATV treatment showed a significant decrease in both the elevated ST wave and CK-MB activity. Moreover, ATV Treatment succeeded to improve oxidative stress biomarkers, tissue NOx, and eNOS protein expression, as well as amelioration of the histological alterations. Conclusion: Pre-treatment with ATV failed to protect against ISO-induced damage. This might suggest a synergistic pro-oxidant effect upon administration of the pro-oxidant ISO along with ATV as demonstrated by the increased oxidative stress and endothelial dysfunction. On the other side, ATV treatment succeeded to significantly improve oxidative stress biomarkers, endothelial dysfunction and myocardial degeneration.

Keywords: atorvastatin, endothelial dysfunction, isoprenaline, oxidative stress

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Authors: Azzah Aldeghather, Sara Alkhodair

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In the modern urban planning and architecture landscape, with western ideologies and styles becoming the mainstay of experience and definitions globally, the Islamic world requires a methodology that defines its expression, which transcends cultural, societal, and national styles. This paper will propose a methodology as an objective system to define, evaluate and apply traditional Islamic knowledge to Islamic urban planning and architecture, providing the Islamic world with a system to manifest its approach to design. The methodology is expressed as Four Pillars which are based on traditional meanings of Arab words roughly translated as Pillar One: The Principles (Al Mabade’), Pillar Two: The Foundations (Al Asas), Pillar Three: The Purpose (Al Ghaya), Pillar Four: Presence (Al Hadara). Pillar One: (The Principles) expresses the unification (Tawheed) pillar of Islam: “There is no God but God” and is comprised of seven principles listed as: 1. Human values (Qiyam Al Insan), 2. Universal language as sacred geometry, 3. Fortitude© and Benefitability©, 4. Balance and Integration: conjoining the opposites, 5. Man, time, and place, 6. Body, mind, spirit, and essence, 7. Unity of design expression to achieve unity, harmony, and security in design. Pillar Two: The Foundations is based on two foundations: “Muhammad is the Prophet of God” and his relationship to the renaming of Medina City as a prototypical city or place, which defines a center space for collection conjoined by an analysis of the Medina Charter as a base for the humanistic design. Pillar Three: The Purpose (Al Ghaya) is comprised of four criteria: The naming of the design as a title, the intention of the design as an end goal, the reasoning behind the design, and the priorities of expression. Pillar Four: Presence (Al Hadara) is usually translated as a civilization; in Arabic, the root of Hadara is to be present. This has five primary definitions utilized to express the act of design: Wisdom (Hikma) as a philosophical concept, Identity (Hawiya) of the form, and Dialogue (Hiwar), which are the requirements of the project vis-a-vis what the designer wishes to convey, Expression (Al Ta’abeer) the designer wishes to apply, and Resources (Mawarid) available. The Proposal will provide examples, where applicable, of past and present designs that exemplify the manifestation of the Pillars. The proposed methodology endeavors to return Islamic urban planning and architecture design to its a priori position as a leading design expression adaptable to any place, time, and cultural expression while providing a base for analysis that transcends the concept of style and external form as a definition and expresses the singularity of the esoteric “Spiritual” aspects in a rational, principled, and logical manner clearly addressed in Islam’s essence.

Keywords: Islamic architecture, Islamic design, Islamic urban planning, principles of Islamic design

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Authors: Dian Hartiningsih, Miranda Diponegoro, Evita Eddie Singgih

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In facing the 21st century, children need to be prepared in reaching their optimum development level which encompasses all aspect of growth and to achieve the learning goals which include not only knowledge and skill, but also disposition and feeling. Teachers as the forefront of education need to be equipped with the understanding and skill of a learning method which can prepare the children to face this 21st century challenge. Project approach is an approach which utilizes active learning which is beneficial for the children. Subject to this research are kindergarten teachers at Dwi Matra Kindergarten and Kirana Preschool. This research is a quantitative research using before and after study design. The result suggest that through preliminary training program on learning with project approach, the kindergarten teachers ability to explain project approach including understanding, benefit and stages of project approach have increased significantly, the teachers ability to design learning with project approach have also improved significantly. The result of learning design that the teachers had made shows a remarkable result for the first stage of the project approach; however the second and third design result was not as optimal. Challenges faced in the research will be elaborated further in the research discussion.

Keywords: project approach, teacher training, learning method, kindergarten

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Authors: Salma A. El-Marasy, Rehab F. Abdel-Rahman, Reham M. Abd-Elsalam

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The burden of stroke is intensely increasing worldwide. Brain injury following transient or permanent focal cerebral ischemia develops ischemic stroke as a consequence of a complex series of pathophysiological events. The aim of this study is to evaluate the possible neuroprotective effect of a dipeptidyl peptidase-4 inhibitor, vildagliptin, independent on its insulinotropic properties in non-diabetic rats subjected to cerebral ischemia. Anaesthetized Wistar rats were subjected to either left middle cerebral artery occlusion (MCAO) or sham operation followed by reperfusion after 30 min of MCAO. The other three groups were orally administered vildagliptin at 3 dose levels (2.5, 5, 10 mg/kg) for 3 successive weeks before subjected to left focal cerebral ischemia/reperfusion and till the end of the study. Neurological deficit scores and motor activity were assessed 24h following reperfusion. 48h following reperfusion, rats were euthanized and their left brain hemispheres were harvested and used in the biochemical, histopathological, and immunohistochemical investigations. Vildagliptin pretreatment improved neurological score deficit, locomotor activity and motor coordination in MCAO rats. Moreover, vildagliptin reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), phosphotylinosital 3 kinase (PI3K), phosphorylated of protein kinase B (p-AKT), and mechanistic target of rapamycin (mTOR) brain contents in addition to reducing protein expression of caspase-3. Also, vildagliptin showed a dose-dependent attenuation in neuronal cell loss and histopathological alterations in MCAO rats. This study proves that vildagliptin exerted the neuroprotective effect in a dose-dependent manner as shown in amelioration of neuronal cell loss and histopathological damage in MCAO rats, which may be mediated by attenuating neuronal and motor deficits, it’s anti-oxidant property, activation of PI3K/AKT/mTOR pathway and its anti-apoptotic effect.

Keywords: caspase-3, cerebral ischemia, dipeptidyl peptidase-4 inhibitor, oxidative stress, PI3K/AKT/mTOR pathway, rats, vildagliptin

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Authors: Idris Elfeituri

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In the current study, energy and exergy analysis of a 65 MW steam power plant was carried out. This study investigated the effect of variations of overall conductance of the super heater on the performance of an existing steam power plant located in Derna, Libya. The performance of the power plant was estimated by a mathematical modelling which considers the off-design operating conditions of each component. A fully interactive computer program based on the mass, energy and exergy balance equations has been developed. The maximum exergy destruction has been found in the steam generation unit. A 50% reduction in the design value of overall conductance of the super heater has been achieved, which accordingly decreases the amount of the net electrical power that would be generated by at least 13 MW, as well as the overall plant exergy efficiency by at least 6.4%, and at the same time that would cause an increase of the total exergy destruction by at least 14 MW. The achieved results showed that the super heater design and operating conditions play an important role on the thermodynamics performance and the fuel utilization of the power plant. Moreover, these considerations are very useful in the process of the decision that should be taken at the occasions of deciding whether to replace or renovate the super heater of the power plant.

Keywords: Exergy, Super-heater, Fouling; Steam power plant; Off-design., Fouling;, Super-heater, Steam power plant

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Authors: Idan Chiyanzu, Maruping Mangena

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Crude glycerol, a major by-product from the transesterification of triacylglycerides with alcohol to biodiesel, is known to have a broad range of applications. For example, its bioconversion can afford a wide range of chemicals including alcohols, organic acids, hydrogen, solvents and intermediate compounds. In bacteria, the 2-oxoglutarate dioxygenase (2-OGD) enzymes are widely found among the Pseudomonas syringae species and have been recognized with an emerging importance in ethylene formation. However, the use of optimized enzyme function in recombinant systems for crude glycerol conversion to ethylene is still not been reported. The present study investigated the production of ethylene from crude glycerol using engineered E. coli MG1655 and JM109 strains. Ethylene production with an optimized expression system for 2-OGD in E. coli using a codon optimized construct of the ethylene-forming gene was studied. The codon-optimization resulted in a 20-fold increase of protein production and thus an enhanced production of the ethylene gas. For a reliable bioreactor performance, the effect of temperature, fermentation time, pH, substrate concentration, the concentration of methanol, concentration of potassium hydroxide and media supplements on ethylene yield was investigated. The results demonstrate that the recombinant enzyme can be used for future studies to exploit the conversion of low-priced crude glycerol into advanced value products like light olefins, and tools including recombineering techniques for DNA, molecular biology, and bioengineering can be used to allowing unlimited the production of ethylene directly from the fermentation of crude glycerol. It can be concluded that recombinant E.coli production systems represent significantly secure, renewable and environmentally safe alternative to thermochemical approach to ethylene production.

Keywords: crude glycerol, bioethylene, recombinant E. coli, optimization

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Authors: Kika Ioannou Kazamia

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This paper examines the action research cycle of the second phase of longitudinal research on sustainable interior design practices, between two groups of stakeholders, designers and clients. During this phase of the action research, the second step - the change stage - of Lewin’s change management model has been utilized to change values, approaches, and attitudes toward sustainable design practices among the participants. Affective domain learning theory is utilized to attach new values. Learning with the use of information technology, collaborative learning, and problem-based learning are the learning methods implemented toward the acquisition of the objectives. Learning methods, and aims, require the design of interventions with participants' involvement in activities that would lead to the acknowledgment of the benefits of sustainable practices. Interventions are steered to measure participants’ decisions for the worth and relevance of ideas, and experiences; accept or commit to a particular stance or action. The data collection methods used in this action research are observers’ reports, participants' questionnaires, and interviews. The data analyses use both quantitative and qualitative methods. The main beneficial aspect of the quantitative method was to provide the means to separate many factors that obscured the main qualitative findings. The qualitative method allowed data to be categorized, to adapt the deductive approach, and then examine for commonalities that could reflect relevant categories or themes. The results from the data indicate that during the second phase, designers and clients' participants altered their behaviours.

Keywords: design, change, sustainability, learning, practices

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Authors: Tamas Hartvanyi, Zoltan Andras Nagy, Miklos Szabo

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The dynamic and static capacity are two opposing aspect of warehouse design. Static capacity optimization aims to maximize the space-usage for goods storing, while dynamic capacity needs more free place to handling them. They are opposing by the building structure and the area utilization. According to Pareto principle: the 80% of the goods are the 20% of the variety. From the origin of this statement, it worth to store the big amount of same products by fulfill the space with minimal corridors, meanwhile the rest 20% of goods have the 80% variety of the whole range, so there is more important to be fast-reachable instead of the space utilizing, what makes the space fulfillment numbers worse. The warehouse design decisions made in present practice by intuitive and empiric impressions, the planning method is formed to one selected technology, making this way the structure of the warehouse homogeny. Of course the result can’t be optimal for the inhomogeneous demands. A new innovative model based on our research will be introduced in this paper to describe the technic capacities, what makes possible to define optimal cluster of technology. It is able to optimize the space fulfillment and the dynamic operation together with this cluster application.

Keywords: warehouse, warehouse capacity, warehouse design method, warehouse optimization

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Authors: Ehsan Sadie

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Today, the cost of repair and maintenance of structures is very important and by studying the behavior of reinforced concrete structures Will become specified several factors such as : Design and calculation errors, lack of proper implementation of structural changes, the damage caused by the introduction of random loads, concrete corrosion and environmental conditions reduce durability of the structures . Meanwhile building codes alteration also cause changes in the assessment and review of the design and structure rather if necessary will be improved and strengthened in the future.

Keywords: concrete building , expandable cement, honeycombed surface , reinforcement corrosion

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Authors: Amna B. Medani, M. A. Elbadwi Samia, Hassan A. Khalid

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In our study, nine Nubian goat kids were obtained, allotted into three groups, and healthily adapted in pens within the premises of the Veterinary Teaching Hospital, University of Khartoum to be given the oral doses of the dried herb shoots at daily doses of 1 and 5 gm/kg/day with drinking water, while the kids of the control group were left undosed. All goats were slaughtered,if not died, after 35 days. S. argel at the given doses caused signs of arched posture, ruffled hair, shivering and paralysis of limbs. On post mortem, lesions were seen to be hepatic fatty changes, renal necrosis, congested lungs and inflamed intestines. Serum chemistry investigations revealed significant increase (P< 0.05-0.01) in the activities of ALP(alkaline phosphates) and AST( aspartate-aminotransferase) in goats dosed with 5 gm /kg/ day. Also observed were significant increases in inorganic phosphorus and urea concentrations (P < 0.05-0.01) in both dosed goat groups. .Other investigations including the activity of GGT( gamma glutamyltransferase), creatinine, calcium, total protein and albumin illustrated no significant difference from that of the undosed controls. On haematological evaluation , the goat kids dosed with 5 gm/kg/dayshowed a decrease in haemoglobin concentration and red blood cells count of (P < 0.05-0.01).Both groups of dosed goats showed a higher packed cell volume values of (P < 0.05) when compared to the control goats .Mean corpuscular haemoglobin values were not different from those of the control kids. S. argel at the given doses caused signs of arched posture, ruffled hair, shivering and paralysis of limbs. On post mortem, lesions were seen to be hepatic fatty changes, renal necrosis, congested lungs and inflamed intestines. Serum chemistry investigations revealed significant increase (P < 0.05-0.01) in the activities of ALP(alkaline phosphates) and AST( aspartate-aminotransferase) in goats dosed with 5 gm /kg/ day. Also observed were significant increases in inorganic phosphorus and urea concentrations (P < 0.05-0.01) in both dosed goat groups. .Other investigations including the activity of GGT( gamma-glutamyltransferase), creatinine, calcium, total protein and albumin illustrated no significant difference from that of the undosed controls. calcium, total protein and albumin illustrated no significant difference from that of the undosed controls. On haematological evaluation , the goat kids dosed with 5 gm/kg/dayshowed a decrease in haemoglobin concentration and red blood cells count of (P < 0.05-0.01).Both groups of dosed goats showed a higher packed cell volume values of (P < 0.05) when compared to the control goats .Mean corpuscular haemoglobin values were not different from those of the control kids. Data obtained were then discussed to find S. argel irritable to intestines , toxic to the kidney and liver and a haematological mild toxin.Suggestions for future were forwarded.

Keywords: hargal, nubian goats, solenstemma argel, toxicity

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Authors: Yasemin İlkay

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Street is not only a crucial spatial unit in urban design and planning discipline but also the context of walking practice in urban space. Moreover, psychogeography concentrates on both ‘walking’ and, therefore, the differentiated forms of (urban) streets to examine the influence of the built environment on the feelings and attitudes of human beings. This paper focuses on ‘walking practice’ in university campuses with reference to spatial appropriation forms via a psychogeographic lens on the phenomenon of alle in two different cities of Turkey, Ankara, the capital city, and Van, in the eastern part of the country. Alle, as an extension of ‘street’ in university campuses, is the constructive spatial structure in university campuses, and as a result, it should be the (both physical and mental) spine of design policy while conceiving and constructing a university campus. The main question of the paper is: How does the interrelation of ‘campus design’ and ‘walking practice’ on alle penetrate reciprocally on the spatial representations of citizens within their urban daily lives. The body contacts with and at urban space (with other objects and subjects) via its movements and stops; this interaction occurs through the spatial pattern of occupancy and vacancy. Walking practice leads to a set of cognitive mental representations in relation to the repertoire of place attachment and spatial appropriation. University campuses are autonomous and fruitful urban spaces to investigate such an interaction. There are both physical/real and psychogeographic representations of the same urban spaces and urban spatial practices. This separation would indicate the invisible dimensions of the difference between ‘what is conceived’ and ‘what is perceived.’ This study aims to compare and contrast the role of alle in both campus design and spatial appropriation via walking at two differentiated university campuses by collecting the mental representations, doing in-depth interviews, and attending walks with the interviewees by psychogeographic techniques. Campus design and spatial appropriation will be compared [with reference to the conception and perception of alle] in three scales: (1) the historical spatial development stories and design approaches of university campuses, (2) the spatial pattern of campuses on the basis of alle, and (3) sub-behavioral regions of the alle in campuses in relation with mental representations and psychogeographic attentive walks. The sub-questions of the research are: [1] How and why do the design approaches differentiate in two university campuses in Turkey, [2] How the interrelation among alle design and spatial appropriation differs in these two cases, and [3] What do the differentiated gaps among real and psychographic maps indicate about the design and spatial appropriation interrelation. METU, as a well-designed, readable campus with its alle, promise a rich walking practice with in-depth and fruitful spatial appropriation regions; however, Van YYÜ limits both the practice and place attachment with its partial design with an alle which is later added to the campus. This research both displays the role of alle in the campus design, walking practice and spatial appropriation and opens a new methodological path to discover hidden knowledge within urban spaces.

Keywords: alle, campus design, cognitive geography, psychogeography, spatial appropriation, Turkey

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Authors: Jenin Zidan

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This research paper investigates how planning, urban design, and architectural decisions affect the long-term environmental sustainability of residential buildings. The study, which focuses on the Al-Malaz District in Riyadh, Saudi Arabia, looks into how strategic planning, innovative urban design, and sustainable architectural practices might help mitigate environmental concerns and promote sustainable development in rapidly growing cities. This study attempts to shed light on the interplay of urban planning, design, and architecture in constructing sustainable residential environments by conducting a thorough examination of case studies and empirical data.

Keywords: urban planning, sustainable architecture, urban environmental challenge, residential buildings, villa house type

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Authors: Ian Campbell, Gillian Mitchell, Paul James, Na Li, Ella Thompson

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The genetic cause of the majority of multiple-case breast cancer families remains unresolved. Next generation sequencing has emerged as an efficient strategy for identifying predisposing mutations in individuals with inherited cancer. We are conducting whole exome sequence analysis of germ line DNA from multiple affected relatives from breast cancer families, with the aim of identifying rare protein truncating and non-synonymous variants that are likely to include novel cancer predisposing mutations. Data from more than 200 exomes show that on average each individual carries 30-50 protein truncating mutations and 300-400 rare non-synonymous variants. Heterogeneity among our exome data strongly suggest that numerous moderate penetrance genes remain to be discovered, with each gene individually accounting for only a small fraction of families (~0.5%). This scenario marks validation of candidate breast cancer predisposing genes in large case-control studies as the rate-limiting step in resolving the missing heritability of breast cancer. The aim of this study is to screen genes that are recurrently mutated among our exome data in a larger cohort of cases and controls to assess the prevalence of inactivating mutations that may be associated with breast cancer risk. We are using the Agilent HaloPlex Target Enrichment System to screen the coding regions of 168 genes in 1,000 BRCA1/2 mutation-negative familial breast cancer cases and 1,000 cancer-naive controls. To date, our interim analysis has identified 21 genes which carry an excess of truncating mutations in multiple breast cancer families versus controls. Established breast cancer susceptibility gene PALB2 is the most frequently mutated gene (13/998 cases versus 0/1009 controls), but other interesting candidates include NPSR1, GSN, POLD2, and TOX3. These and other genes are being validated in a second cohort of 1,000 cases and controls. Our experience demonstrates that beyond PALB2, the prevalence of mutations in the remaining breast cancer predisposition genes is likely to be very low making definitive validation exceptionally challenging.

Keywords: predisposition, familial, exome sequencing, breast cancer

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Authors: Zhehao Zhang

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Walking has become an indispensable and sustainable way of travel for college students in their daily lives; campus street is an important carrier for students to walk and take part in a variety of activities, improving the walkability of campus streets plays an important role in optimizing the quality of campus space environment, promoting the campus walking system and inducing multiple walking behaviors. The purpose of this paper is to explore the effect of campus layout, facility distribution, and location site selection on the walkability of campus streets, and assess the street design qualities from the elements of imageability, enclosure, complexity, transparency, and human scale, and further examines the relationship between street-level urban design perceptual qualities and walkability and its effect on walking behavior in the campus. Taking Tianjin University as the research object, this paper uses the optimized walk score method based on walking frequency, variety, and distance to evaluate the walkability of streets from a macro perspective and measures the urban design qualities in terms of the calculation of street physical environment characteristics, as well as uses behavior annotation and street image data to establish temporal and spatial behavior database to analyze walking activity from the microscopic view. In addition, based on the conclusions, the improvement and design strategy will be presented from the aspects of the built walking environment, street vitality, and walking behavior.

Keywords: walkability, streetscapes, pedestrian activity, walk score

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Authors: Yan Wang, Wei Wu

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In recent years, with the gradual change of Chinese urban development mode from 'incremental development' to 'stock-based renewal', the urban design method of ‘grand scene’ in the past could only cope with the planning and construction of incremental spaces such as new towns and new districts, while the problems involved in the renewal of the stock lands such as historic blocks of ancient cities are more complex. 'Simplified' large-scale demolition and construction may lead to the damage of the ancient city's texture and the overall cultural atmosphere; thus it is necessary to re-explore the urban design path of historical blocks in the conservation context of the ancient city. Through the study of the cultural context of the ancient city of Suzhou in China and the interpretation of its current characteristics, this paper explores the methods and paths for the renewal of historical and cultural blocks in the ancient city. It takes No. 12 and No. 13 historical blocks in the ancient city of Suzhou as examples, coordinating the spatial layout and the landscape and shaping the regional characteristics to improve the quality of the ancient city's life. This paper analyses the idea of conservation and regeneration from the aspects of culture, life, business form, and transport. Guided by the planning concept of ‘block repair and cultural infiltration’, it puts forward the urban design path of ‘conservation priority, activation and utilization, organic renewal and strengthening guidance’, with a view to continuing the cultural context and stimulating the vitality of ancient city, so as to realize the integration of history, modernity, space and culture. As a rare research on urban design in the scope of Suzhou ancient city, the paper expects to explore the concepts and methods of urban design for the historic blocks on the basis of the conservation of the history, space, and culture and provides a reference for other similar types of urban construction.

Keywords: historical block, Suzhou ancient city, stock-based renewal, urban design

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Authors: Ying Yu, Wen-Chi Kuo, Tung-Jung Sung

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The Product-Service System (PSS) has received widespread attention due to the increasing global competition in manufacturing and service markets. Today’s smart products and services are driven by Internet of things (IoT) technologies which will promote the transformation from traditional PSS to smart PSS. Although the smart PSS has some of technological achievements in businesses, it often ignores the real demands of target users when using products and services. Therefore, designers should know and learn the User Experience (UX) of smart products, services and systems. However, both of academia and industry still lack relevant development experience of smart PSS since it is an emerging field. In doing so, this is a case study of Xiaomi’s Chunmi, the largest IoT platform in the world, and addresses the two major issues: (1) why Chunmi should develop smart PSS strategies with UX; and (2) how Chunmi could successfully implement the strategic objectives of smart PSS through the design. The case study results indicated that: (1) the smart PSS can distinguish competitors by their unique UX which is difficult to duplicate; (2) early user engagement is crucial for the success of smart PSS; and (3) interaction, expectation, and enjoyment can be treated as a three-dimensional evaluation of UX design for smart PSS innovation. In conclusion, the smart PSS can gain competitive advantages through good UX design in the market.

Keywords: design, smart PSS, user experience, user engagement

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Authors: Boudjedra Abderrahim, Toumi Salah, Boutalbi Mostefa, Frihi Mohammed

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Nowadays, using the advancement of technology in semiconductor device fabrication, many transistors can be integrated to a single chip (VLSI). Although the growth chip density potentially eases systems-on-chip (SoCs) integrating thousands of processing element (PE) such as memory, processor, interfaces cores, system complexity, high-performance interconnect and scalable on-chip communication architecture become most challenges for many digital and embedded system designers. Networks-on-chip (NoCs) becomes a new paradigm that makes possible integrating heterogeneous devices and allows many communication constraints and performances. In this paper, we are interested for good performance and low area for implementation and a behavioral modeling of network on chip mesh topology design using VHDL hardware description language with performance evaluation and FPGA implementation results.

Keywords: design, implementation, communication system, network on chip, VHDL

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

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

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

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Authors: Mark Bezner, Shani Deri, Tom Trigano, Kfir Ben-Harush

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Intermediate filament (IF) proteins-based fibers are among the toughest fibers in nature, as was shown by native hagfish slime threads and by synthetic fibers that are based on type V IF-proteins, the nuclear lamins. It is assumed that their mechanical performance stems from two major factors: (1) the transition from elastic -helices to stiff-sheets during tensile load; and (2) the specific organization of the coiled-coil proteins into a hierarchical network of nano-filaments. Here, we investigated the interrelationship between these two factors by using wet-spun fibers based on C. elegans (Ce) lamin. We found that Ce-lamin fibers, whether assembled in aqueous or alcoholic solutions, had the same nonlinear mechanical behavior, with the elastic region ending at ~5%. The pattern of the transition was, however, different: the ratio between -helices and -sheets/random coils was relatively constant until a 20% strain for fibers assembled in an aqueous solution, whereas for fibers assembled in 70% ethanol, the transition ended at a 6% strain. This structural phenomenon in alcoholic solution probably occurred through the transition between compacted and extended conformation of the random coil, and not between -helix and -sheets, as cycle analyses had suggested. The different transition pattern can also be explained by the different higher order organization of Ce-lamins in aqueous or alcoholic solutions, as demonstrated by introducing a point mutation in conserved residue in Ce-lamin gene that alter the structure of the Ce-lamins’ nano-fibrils. In addition, biomimicking the layered structure of silk and hair fibers by coating the Ce-lamin fiber with a hydrophobic layer enhanced fiber toughness and lead to a reversible transition between -helix and the extended conformation. This work suggests that different hierarchical structures, which are formed by specific assembly conditions, lead to diverse secondary structure transitions patterns, which in turn affect the fibers’ mechanical properties.

Keywords: protein-based fibers, intermediate filaments (IF) assembly, toughness, structure-property relationships

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