Search results for: protein design

Authors: Ahlam H. Mahmoud, Samir F. Zohny, Ibrahim H. Boraia, Faten S. Bayoumic, Eman Eissa

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Hepatocellular carcinoma is one of the most common cancers worldwide and is known to be resistant to conventional chemotherapy. Therefore, we aimed to assess the Salsola inermis extract as a novel chemopreventive and/or therapeutic agent against N-nitrosodiethylamine (DNE)/phenobarbital (PB)-induced hepatocarcinogenesis in rats. Adult male Wistar albino rats were divided into five groups: group1 rats were served as normal controls; group 2 rats were injected intraperitoneally with S. inermis extract (100 mg/kg body weight/day) for 20 weeks; group 3 rats were subjected to two-phase hepatocarcinogenic regimen (initiation of hepatocarcinogenesis was performed by a single intraperitoneal injection of DEN at a dose of 200 mg/kg body weight, 2 weeks later, the carcinogenic effect was promoted by supplementation of rats with 0.05% PB for 16 weeks); group 4 rats were injected intraperitoneally with S. inermis extract 2 weeks prior to the injection of DEN, the daily injection of S. inermis extract was then continued for 18 weeks along with two-phase hepatocarcinogenic regimen (chemoprevention group); and group 5 rats were subjected to the two-phase hepatocarcinogenic regimen, and then, the animals were injected intraperitoneally with S. inermis extract for 4 weeks (treatment group). The activities of serum liver enzymes and levels of total bilirubin, conjugated bilirubin, α-fetoprotein, vascular endothelial growth factor (VEGF) and soluble intercellular adhesion molecule-1 (sICAM-1) in serum were decreased in chemopreventive and treated rats compared with DEN/PB-administered rats. Interestingly, the serum levels of total protein and albumin were normalized in chemopreventive and treated rats. Moreover, the majority of chemopreventive and treated rats showed an almost normal histological pattern of liver. In conclusion, S. inermis extract possessed chemopreventive and therapeutic activities against hepatocarcinogenesis in rats partially through the inhibition of VEGF and sICAM-1.

Keywords: Salsola inermis extract, hepatocarcinogenesis, α–fetoprotein, VEGF, sICAM-1

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Authors: Gloria Pinilla, Jose Manuel Baena, Patricia Gálvez-Martín, Juan Antonio Marchad

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Cartilage is a dense connective tissue with limited self-repair properties. Currently, the therapeutic use of autologous or allogenic chondrocytes makes up an alternative therapy to the pharmacological treatment. The design of a bioprinted 3D cartilage with chondrocytes and biodegradable biomaterials offers a new therapeutic alternative able of bridging the limitations of current therapies in the field. We have developed an enhanced printing processes-Injection Volume Filling (IVF) to increase the viability and survival of the cells when working with high-temperature thermoplastics without the limitation of the scaffold geometry in contact with cells. We have demonstrated the viability of the printing process using chondrocytes for cartilage regeneration. This development will accelerate the clinical uptake of the technology and overcomes the current limitation when using thermoplastics as scaffolds. An alginate-based hydrogel combined with human chondrocytes (isolated from osteoarthritis patients) was formulated as bioink-A and the polylactic acid as bioink-B. The bioprinting process was carried out with the REGEMAT V1 bioprinter (Regemat 3D, Granada-Spain) through a IVF. The printing capacity of the bioprinting plus the viability and cell proliferation of bioprinted chondrociytes was evaluated after five weeks by confocal microscopy and Alamar Blue Assay (Biorad). Results showed that the IVF process does not decrease the cell viability of the chondrocytes during the printing process as the cells do not have contact with the thermoplastic at elevated temperatures. The viability and cellular proliferation of the bioprinted artificial 3D cartilage increased after 5 weeks. In conclusion, this study demonstrates the potential use of Regemat V1 for 3D bioprinting of cartilage and the viability of bioprinted chondrocytes in the scaffolds for application in regenerative medicine.

Keywords: cartilage regeneration, bioprinting, bioink, scaffold, chondrocyte

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Authors: Jenan Abu Qadourah

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With the depletion of traditional fossil resources and the growing human population, it is now more important than ever to reduce our energy usage and harmful emissions. In the Mediterranean region, the intense solar radiation contributes to summertime overheating, which raises energy costs and building carbon footprints, alternatively making it suitable for the installation of solar energy systems. In urban settings, where multi-story structures predominate and roof space is limited, photovoltaic integrated shading devices (PVSD) are a clean solution for building designers. However, incorporating photovoltaic (PV) systems into a building's envelope is a complex procedure that, if not executed correctly, might result in the PV system failing. As a result, potential PVSD design solutions must be assessed based on their overall energy performance from the project's early design stage. Therefore, this paper aims to investigate and compare the possible impact of various PVSDs on the energy performance of new apartments in the Mediterranean region, with a focus on Amman, Jordan. To achieve the research aim, computer simulations were performed to assess and compare the energy performance of different PVSD configurations. Furthermore, an energy index was developed by taking into account all energy aspects, including the building's primary energy demand and the PVSD systems' net energy production. According to the findings, the PVSD system can meet 12% to 43% of the apartment building's electricity needs. By highlighting the potential interest in PVSD systems, this study aids the building designer in producing more energy-efficient buildings and encourages building owners to install PV systems on the façade of their buildings.

Keywords: photovoltaic integrated shading device, solar energy, architecture, energy performance, simulation, overall energy index, Jordan

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Authors: H. Haryati, A. Nor Azura

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Over the turn of the century, the advertising landscape has evolved significantly, from print media to digital media. In line with the shift to the advanced science and technology dramatically shake the framework of societies Fifth Industrial Revolution (IR5.0), technological endeavors have increased exponentially, which influenced user interaction more inspiring through online advertising that intentionally leads to buying behavior. Users are more accustomed to interactive content that responds to their actions. Thus, immersive experience has transformed into a new engagement experience To centennials. The purpose of this paper is to investigate pleasure and arousal as the fundamental elements of consumer emotions and affective responses to marketing stimuli. A quasi-experiment procedure will be adopted in the research involving 40 undergraduate students in Nilai, Malaysia. This study employed a 2 (celebrity endorser vs. Social media influencer) X 2 (high and low visual complexity) factorial between-subjects design. Participants will be exposed to a printed version depicting a fashion product endorsed by a celebrity and social media influencers, presented in high and low levels of visual complexity. While the questionnaire will be Distributing during the lab test session is used to control their honesty, real feedback, and responses through the latest Instagram design and engagement. Therefore, the research aims to define the immersive experience on Instagram and the interaction between pleasure and arousal. An advertisement that evokes pleasure and arousal will be likely getting more attention from the target audience. This is one of the few studies comparing the endorses in Instagram advertising. Also, this research extends the existing knowledge about the immersive visual complexity in the context of social media advertising.

Keywords: immersive visual experience, instagram, pleasure, arousal

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Authors: Atikah Nurhayati, Asep A. Handaka

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Indonesia is a world’s major fish producer which can feed not only its citizens but also the people of the world. Currently, the total annual production is 11 tons and expected to double by the year of 2050. Given the potential, fishery has been an important part of the national food security system in Indonesia. Despite such a potential, a big challenge is facing the Indonesians in making fish the reliable source for their food, more specifically source of protein intake. The long geographic distance between the fish production centers and the consumer concentrations has prevented effective supply chain from producers to consumers and therefore demands a good logistic system. This paper is based on our research, which aimed at analyzing the fish supply chain and is to suggest relevant improvement to the chain. The research was conducted in the Year of 2016 in selected locations of Java Island, where intensive transaction on fishery commodities occur. Data used in this research comprises secondary data of time series reports on production and distribution and primary data regarding distribution aspects which were collected through interviews with purposively selected 100 respondents representing fishers, traders and processors. The data were analyzed following the supply chain management framework and processed following logistic regression and validity tests. The main findings of the research are as follows. Firstly, it was found that improperly managed connectivity and logistic chain is the main cause for insecurity of availability and affordability for the consumers. Secondly, lack of quality of most local processed products is a major obstacle for improving affordability and connectivity. The paper concluded with a number of recommended strategies to tackle the problem. These include rationalization of the length of the existing supply chain, intensification of processing activities, and improvement of distribution infrastructure and facilities.

Keywords: fishery, food security, logistic, supply chain

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Authors: Emmanuel Mkambankhani, Tiwonge Manda

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Software platform architecture includes system components, their relationships, and design, as well as evolution principles. Software architecture and documentation affect a platform's customizability and openness to external innovators, thus affecting developer productivity. Malawi Point of Care (POC) Electronic Medical Records System (EMRS) follows some architectural design standards, but it lacks third-party innovators and is difficult to customize as compared to CommCare and District Health Information System 2 (DHIS2). Improving software architecture and documentation for the Malawi POC will increase productivity and third-party contributions. A conceptual framework based on Generativity and Boundary Resource Model (BRM) was used to compare the three platforms. Interviews, observations, and document analysis were used to collect primary and secondary data. Themes were found by analyzing qualitative and quantitative data, which led to the following results. Configurable, flexible, and cross-platform software platforms and the availability of interfaces (Boundary Resources) that let internal and external developers interact with the platform's core functionality, hence boosting developer productivity. Furthermore, documentation increases developer productivity, while its absence inhibits the use of resources. The study suggests that the architecture and openness of the Malawi POC EMR software platform will be improved by standardizing web application program interfaces (APIs) and making interfaces that can be changed by the user. In addition, increasing the availability of documentation and training will improve the use of boundary resources, thus improving internal and third-party development productivity.

Keywords: health systems, configurable platforms, software architecture, software documentation, software development productivity

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Authors: Xavier Bertrand, Alexandre Cayrel

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The early phase of an aircraft development is instrumental as it really drives the potential of a new concept. Any weakness in the high-level design (wing planform, moveable surfaces layout etc.) will be extremely difficult and expensive to recover later in the aircraft development process. Aerodynamic evaluation in this very early development phase is driven by two main criteria: a short lead-time to allow quick iterations of the geometrical design, and a high quality of the calculations to get an accurate & reliable assessment of the current status. These two criteria are usually quite contradictory. Actually, short lead time of a couple of hours from end-to-end can be obtained with very simple tools (semi-empirical methods for instance) although their accuracy is limited, whereas higher quality calculations require heavier/more complex tools, which obviously need more complex inputs as well, and a significantly longer lead time. At this point, the choice has to be done between accuracy and lead-time. A brand new approach has been developed within Airbus, aiming at obtaining quickly high quality evaluations of the aerodynamic of an aircraft. This methodology is based on a joint use of Surrogate Modelling and a lifting line code. The Surrogate Modelling is used to get the wing sections characteristics (e.g. lift coefficient vs. angle of attack), whatever the airfoil geometry, the status of the moveable surfaces (aileron/spoilers) or the high-lift devices deployment. From these characteristics, the lifting line code is used to get the 3D effects on the wing whatever the flow conditions (low/high Mach numbers etc.). This methodology has been applied successfully to a concept of medium range aircraft.

Keywords: aerodynamics, lifting line, surrogate model, CFD

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Authors: C. M. Nur Syazwani, M. K. Ahmad Imran, Rizal E. M. Nasir

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The study on BWB UV begins in UiTM since 2005 and three designs have been studied and published. The latest designs are Baseline-III and inspired by birds that have features and aerodynamics behaviour of cruising birds without flapping capability. The aircraft featuring planform and configuration are similar to the bird. Baseline-III has major flaws particularly in its low lift-to-drag ratio, stability and issues regarding limited controllability. New design known as Baseline-IV replaces straight, swept wing to delta wing and have a broader tail compares to the Baseline-III’s. The objective of the study is to investigate aerodynamics of Baseline-IV bird-inspired BWB aircraft. This will be achieved by theoretical calculation and wind tunnel experiments. The result shows that both theoretical and wind tunnel experiments of Baseline-IV graph of CL and CD versus alpha are quite similar to each other in term of pattern of graph slopes and values. Baseline-IV has higher lift coefficient values at wide range of angle of attack compares to Baseline-III. Baseline-IV also has higher maximum lift coefficient, higher maximum lift-to-drag and lower parasite drag. It has stable pitch moment versus lift slope but negative moment at zero lift for zero angle-of-attack tail setting. At high angle of attack, Baseline-IV does not have stability reversal as shown in Baseline-III. Baseline-IV is proven to have improvements over Baseline-III in terms of lift, lift-to-drag ratio and pitch moment stability at high angle-of-attack.

Keywords: blended wing-body, bird-inspired blended wing-body, aerodynamic, stability

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Authors: Azin Shakibabarough, Mojtaba Valinejadshoubi, Ashutosh Bagchi

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Catastrophic bridge failure happens due to the lack of inspection, lack of design and extreme events like flooding, an earthquake. Bridge Management System (BMS) is utilized to diminish such an accident with proper design and frequent inspection. Visual inspection cannot detect any subsurface defects, so using Non-Destructive Evaluation (NDE) techniques remove these barriers as far as possible. Among all NDE techniques, Ground Penetrating Radar (GPR) has been proved as a highly effective device for detecting internal defects in a reinforced concrete bridge deck. GPR is used for detecting rebar location and rebar corrosion in the reinforced concrete deck. GPR profile is composed of hyperbola series in which sound hyperbola denotes sound rebar and blur hyperbola or signal attenuation shows corroded rebar. Interpretation of GPR images is implemented by numerical analysis or visualization. Researchers recently found that interpretation through visualization is more precise than interpretation through numerical analysis, but visualization is time-consuming and a highly subjective process. Automating the interpretation of GPR image through visualization can solve these problems. After interpretation of all scans of a bridge, condition assessment is conducted based on the generated corrosion map. However, this such a condition assessment is not objective and precise. Condition assessment based on structural integrity and strength parameters can make it more objective and precise. The main purpose of this study is to present an automated interpretation method of a reinforced concrete bridge deck through a visualization technique. In the end, the combined analysis of the structural condition in a bridge is implemented.

Keywords: bridge condition assessment, ground penetrating radar, GPR, NDE techniques, visualization

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Authors: Sutapa Som Chaudhury, Chitrangada Das Mukhopadhyay

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Alzheimer’s disease is a well-known form of dementia since its discovery in 1906. Current Food and Drug Administration approved medications e.g. cholinesterase inhibitors, memantine offer modest symptomatic relief but do not play any role in disease modification or recovery. In last three decades many small molecules, chaperons, synthetic peptides, partial β-secretase enzyme blocker have been tested for the development of a drug against Alzheimer though did not pass the 3rd clinical phase trials. Here in this study, we designed a PEGylated, aminogenic, tripeptidic polymer with two different molecular weights based on the aggregation prone amino acid sequence 17-20 in amyloid beta (Aβ) 1-42. Being conjugated with poly-ethylene glycol (PEG) which self-assembles into hydrophilic nanoparticles, these PEGylated tripeptides constitute a very good drug delivery system crossing the blood brain barrier while the peptide remains protected from proteolytic degradation and non-specific protein interactions. Moreover, being completely aminogenic they would not raise any side effects. These peptide inhibitors were evaluated for their effectiveness against Aβ42 fibrillation at an early stage of oligomer to fibril formation as well as preformed fibril clearance via Thioflavin T (ThT) assay, dynamic light scattering analyses, atomic force microscopy and scanning electron microscopy. The inhibitors were proved to be safe at a higher concentration of 20µM by the reduction assay of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye. Moreover, SHSY5Y neuroblastoma cells have shown a greater survivability when treated with the inhibitors following Aβ42 fibril and oligomer treatment as compared with the control Aβ42 fibril and/or oligomer treated neuroblastoma cells. These make the peptidic inhibitors a promising compound in the aspect of the discovery of alternative medication for Alzheimer’s disease.

Keywords: Alzheimer’s disease, alternative medication, amyloid beta, PEGylated peptide

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Authors: Aditya Arya, Hairin Taha, Ataul Karim Khan, Nayiar Shahid, Hapipah Mohd Ali, Mustafa Ali Mohd

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This study has investigated the antidiabetic and antioxidant potential of Pseudovaria macrophylla bark extract on streptozotocin–nicotinamide induced type 2 diabetic rats. LCMS-QTOF and NMR experiments were done to determine the chemical composition in the methanolic bark extract. For in vivo experiments, the STZ (60 mg/kg/b.w, 15 min after 120 mg/kg/1 nicotinamide, i.p.) induced diabetic rats were treated with methanolic extract of Pseuduvaria macrophylla (200 and 400 mg/kg∙bw) and glibenclamide (2.5 mg/kg) as positive control respectively. Biochemical parameters were assayed in the blood samples of all groups of rats. The pro-inflammatory cytokines, antioxidant status and plasma transforming growth factor βeta-1 (TGF-β1) were evaluated. The histological study of the pancreas was examined and its expression level of insulin was observed by immunohistochemistry. In addition, the expression of glucose transporters (GLUT 1, 2 and 4) were assessed in pancreas tissue by western blot analysis. The outcomes of the study displayed that the bark methanol extract of Pseuduvaria macrophylla has potentially normalized the elevated blood glucose levels and improved serum insulin and C-peptide levels with significant increase in the antioxidant enzyme, reduced glutathione (GSH) and decrease in the level of lipid peroxidation (LPO). Additionally, the extract has markedly decreased the levels of serum pro-inflammatory cytokines and transforming growth factor beta-1 (TGF-β1). Histopathology analysis demonstrated that Pseuduvaria macrophylla has the potential to protect the pancreas of diabetic rats against peroxidation damage by downregulating oxidative stress and elevated hyperglycaemia. Furthermore, the expression of insulin protein, GLUT-1, GLUT-2 and GLUT-4 in pancreatic cells was enhanced. The findings of this study support the anti-diabetic claims of Pseudovaria macrophylla bark.

Keywords: diabetes mellitus, Pseuduvaria macrophylla, alkaloids, caffeic acid

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Authors: Paria Saadatjoo

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Given that HVAC systems are the main sources of carbon dioxide producers, developing ways to reduce dependence on these systems and making use of natural resources is too important to achieve environmentally friendly buildings. A major part of building potential in terms of using natural energy resources depends on its physical features. So architectural decisions at the first step of the design process can influence the building's energy efficiency significantly. Implementation of semi-open spaces into solid apartment blocks inspired by the concept of courtyard in ancient buildings as a passive cooling strategy is currently enjoying great popularity. However, the analysis of these features and their effect on wind behavior at initial design steps is a difficult task for architects. The main objective of this research was to investigate the influence of semi-open to closed space ratio on airflow patterns in and around midrise buildings and introduce the best ratio in terms of harnessing natural ventilation. The main strategy of this paper was semi-experimental, and the research methodology was descriptive statistics. At the first step, by changing the terrace area, 6 models with various open to closed space ratios were created. These forms were then transferred to CFD software to calculate the primary indicators of natural ventilation potentials such as wind force coefficient, air flow rate, age of air distribution, etc. Investigations indicated that modifying the terrace area and, in other words, the open to closed space ratio influenced the wind force coefficient, airflow rate, and age of air distribution.

Keywords: natural ventilation, wind, midrise, open space, energy

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Authors: Magarò Floriana, Zinno Raffaele

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Since 2009, with the coming into force of the January 14, 2008 Ministerial Decree "New technical standards for construction", and the explanatory ministerial circular N°.617 of February 2, 2009, the question of seismic hazard and the design of seismic-resistant structures in Italy has acquired increasing importance. One of the most discussed aspects in recent Italian and international scientific literature concerns the dynamic interaction between land and structure, and the effects which dynamic coupling may have on individual buildings. In effect, from systems dynamics, it is well known that resonance can have catastrophic effects on a stimulated system, leading to a response that is not compatible with the previsions in the design phase. The method used in this study to estimate the frequency of oscillation of the structure is as follows: the analysis of HVSR (Horizontal to Vertical Spectral Ratio) relations. This allows for evaluation of very simple oscillation frequencies for land and structures. The tool used for data acquisition is an experimental digital tromograph. This is an engineered development of the experimental Languamply RE 4500 tromograph, equipped with an engineered amplification circuit and improved electronically using extremely small electronic components (size of each individual amplifier 16 x 26 mm). This tromograph is a modular system, completely "free" and "open", designed to interface Windows, Linux, OSX and Android with the outside world. It an amplifier designed to carry out microtremor measurements, yet which will also be useful for seismological and seismic measurements in general. The development of single amplifiers of small dimension allows for a very clean signal since being able to position it a few centimetres from the geophone eliminates cable “antenna” phenomena, which is a necessary characteristic in seeking to have signals which are clean at the very low voltages to be measured.

Keywords: microtremor, HVSR, tromograph, structural engineering

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Authors: Nonso Ochinanwata, Patrick Oseloka Ezepue

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This paper explores challenges and prospects in Nigerian higher education. The paper develops an integrated business model that aimed to innovate Nigeria higher education system. A survey and semi-structured interview among Nigerian higher education academics, students and graduates are used to explore the challenges and prospects. The study provides a comparison between lecturers, students and graduates opinions to evaluate challenges and prospects in Nigerian higher institutions. The study found to achieve efficient and effectiveness innovation in Nigerian higher education, there is a need for higher institutions to collaborate with industry professionals and other stakeholders such as company management, and government policy makers in designing higher education institutions curricula. The study found that the curriculum design and delivery need to blend theoretical understanding and real-life experience from industry, and with social cultural influences related to Nigerian environment. This will enable lecturers to organise their teaching and assessments such that students can learn around theoretical and practical study themes. The curriculum design and delivery need to link the core ideas to challenging problems in society, nationally and globally. Hence, this approach will support business start-ups and social entrepreneurship which resolve key societal problems. The study suggests that higher education executives, directors, deans, head of departments, and even individual academics need to emulate innovative business managers to create value-adding products and services from innovative research and academic work.

Keywords: higher education, curriculum innovation, business model innovation, teaching and research excellence, economic development

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Authors: Pramod Jagtap, Kisan Jadhav, Neha Dand

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Risperidone (RISP) is an antipsychotic agent and has low water solubility and nontargeted delivery results in numerous side effects. Hence, an attempt was made to develop SLNs hydrogel for intranasal delivery of RISP to achieve maximum bioavailability and reduction of side effects. RISP loaded SLNs composed of 1.65% (w/v) lipid mass were produced by high shear homogenization (HSH) coupled ultrasound (US) method using glyceryl monostearate (GMS) or Imwitor 900K (solid lipid). The particles were loaded with 0.2% (w/v) of the RISP & surface-tailored with a 2.02% (w/v) non-ionic surfactant Tween® 80. Optimization was done using 32 factorial design using Design Expert® software. The prepared SLNs dispersion incorporated into Polycarbophil AA1 hydrogel (0.5% w/v). The final gel formulation was evaluated for entrapment efficiency, particle size, rheological properties, X ray diffraction, in vitro diffusion, ex vivo permeation using sheep nasal mucosa and histopathological studies for nasocilliary toxicity. The entrapment efficiency of optimized SLNs was found to be 76 ± 2 %, polydispersity index <0.3., particle size 278 ± 5 nm. This optimized batch was incorporated into hydrogel. The pH was found to be 6.4 ± 0.14. The rheological behaviour of hydrogel formulation revealed no thixotropic behaviour. In histopathology study, there was no nasocilliary toxicity observed in nasal mucosa after ex vivo permeation. X-ray diffraction data shows drug was in amorphous form. Ex vivo permeation study shows controlled release profile of drug.

Keywords: ex vivo, particle size, risperidone, solid lipid nanoparticles

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Authors: Yun-Chin Chung, Nileema Divate, Gen-Hung Chen, Pei-Ru Huang, Rupesh Divate

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Many environmental factors, such as glucose concentration, ethanol, temperature, osmotic pressure and pH, decrease the production rate of ethanol using yeast as a starter. Fermentation starters with high tolerance to various stresses are always demanded for brewing industry. Trehalose, a storage carbohydrate in cell wall of yeast, plays an important role in tolerance of environmental stress by preserving integrity of plasma membrane and stabilizing proteins. Furan aldehydes are toxic to yeast and the growth rate of yeast is significantly reduced if furan aldehydes were present in the fermentation medium. In yeast, aldehyde reductase is involved in the detoxification of reactive aldehydes and consequently the growth of yeast is improved. The aims of this study were to construct a genetic recombinant Saccharomyces cerevisiae or Pichia pastoris with furfural and HMF degrading and high ethanol tolerance capacities. Yeast strains were engineered by genetic recombination for overexpression of trehalose-6-phosphate synthase gene (tps1) and aldehyde reductase gene (ari1). TPS1 gene was cloned from S. cerevisiae by reverse transcription-polymerase chain reaction (RT-PCR) and then ligated with pGAPZαC vector. The constructed vector, pGAPZC-tps1, was transformed to recombinant yeasts strain with overexpression of ari1. The transformants with pGAPZC-tps1-ari1 were generated called STA (S. cerevisiae) and PTA (P. pastoris) with overexpression of tps1, ari1. PCR with tps1-specific primers and western blot with his-tag confirmed the gene insertion and protein expression of tps1 in the transformants, respectively. The neutral trehalase gene (nth1) of STA was successfully deleted and the novel strain STAΔN will be used for further study, including the measurement of trehalose concentration and ethanol, furfural tolerance assay.

Keywords: genetic recombinant, yeast, ethanol tolerance, trehalase, aldehyde reductase

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Authors: Merve Sagiroglu

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The earthquake-resistant steel structure design is required taking into account the behavior of beam-column connections besides the basic properties of the structure such as material and geometry. Beam-column connections play an important role in the behavior of frame systems. Taking into account the behaviour of connection in analysis and design of steel frames is important due to presenting the actual behavior of frames. So, the behavior of the connections should be well known. The most important force which transmitted by connections in the structural system is the moment. The rotational deformation is customarily expressed as a function of the moment in the connection. So, the moment-rotation curves are the best expression of behaviour of the beam-to-column connections. The designed connections form various moment-rotation curves according to the elements of connection and the shape of placement. The only way to achieve this curve is with real-scale experiments. The experiments of some connections have been carried out partially and are formed in the databank. It has been formed the models using this databank to express the behavior of connection. In this study, theoretical studies have been carried out to model a real behavior of the top and seat angles connections with angles. Two stiffeners in the top and seat angle to increase the stiffness of the connection, and two stiffeners in the beam web to prevent local buckling are used in this beam-to-column connection. Mathematical models have been performed using the database of the beam-to-column connection experiments previously by authors. Using the data of the tests, it has been aimed that analytical expressions have been developed to obtain the moment-rotation curve for the connection details whose test data are not available. The connection has been dimensioned in various shapes and the effect of the dimensions of the connection elements on the behavior has been examined.

Keywords: top and seat angle connection, stiffener, moment-rotation curves, analytical study

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Authors: Neelma Ashraf

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Actinomycetes, particularly genus Streptomyces is of great importance due to their role in the discovery of new natural products, particularly antimicrobial secondary metabolites in the medicinal science and biotechnology industry. Different Streptomyces strains were isolated from Helianthus annuus plants and tested for antibacterial and antifungal activities. The most promising five strains were chosen for further investigation, and growth conditions for antibiotic synthesis were optimised. The supernatants were extracted in different solvents, and the extracted products were analyzed using liquid chromatography-mass spectrometry (LC-MS) and biological testing. From one of the potent strains Streptomyces globusus sp. BR123, a compound lavendamycin was identified using these analytical techniques. In addition, this potent strain also produces a strong antifungal polyene compound with a quasimolecular ion of 2072. Streptomyces sp. BR123 was genome sequenced because of its promising antimicrobial potential in order to identify the gene cluster responsible for analyzed compound “lavendamycin”. The genome analysis yielded candidate genes responsible for the production of this potent compound. The genome sequence of 8.15 Mb of Streptomyces sp. isolate BR123 with a GC content of 72.63% and 8103 protein coding genes was attained. Many antimicrobial, antiparasitic, and anticancerous compounds were detected through multiple biosynthetic gene clusters predicted by in-Silico analysis. Though, the novelty of metabolites was determined through the insignificant resemblance with known biosynthetic gene clusters. The current study gives insight into the bioactive potential of Streptomyces sp. isolate BR123 with respect to the synthesis of bioactive secondary metabolites through genomic and spectrometric analysis. Moreover, the comparative genome study revealed the connection of isolate BR123 with other Streptomyces strains, which could expand the knowledge of this genus and the mechanism involved in the discovery of new antimicrobial metabolites.

Keywords: streptomyces, secondary metabolites, genome, biosynthetic gene clusters, high performance liquid chromatography, mass spectrometry

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Authors: Thilini Kananke

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Culinary herbs have long been considered as significant dietary sources of many potential health-promoting compounds. The present research focused on analysis of antimicrobial, antioxidant and physicochemical properties in selected four culinary herbs namely Murraya koenigii (Curry leaves), Pandanus amaryllifolius (Pandan leaves), Cymbopogon citrates (Lemon grass leaves), and Mentha Piperita (Minchi leaves) obtained from several market sites in Ratnapura District, Sri Lanka. The antimicrobial activity of ethanolic, chloroform and distilled water extracts of culinary herbs were evaluated against the strains of Staphylococcus aureus, Salmonella typhi and Shigella spp. Total phenolic content and the radical scavenging activity (using DPPH assay) of culinary herbs were determined. Four heavy metals (Cu, Cd, Pb and Fe) were analyzed in the selected culinary herbs using the atomic absorption spectroscopy (AAS). Proximate compositions of the selected herbs were analyzed using AOAC official methods. Antimicrobial activity of all selected culinary herbs showed relativity high inhibition zones against S. aureus. Pandan leaves showed the least antimicrobial activity against selected bacterial strains compared with other culinary herbs. Both the highest radical scavenging activity (lower IC50 value) and the total phenolic content (25.57 ±3.54µg GAE/100g) were reported in Mentha piperita extract. The highest concentrations of Cu, Fe and Cd were reported in Curry leaves (29.15 mg/kg), Lemon grass leaves (257.98 mg/kg) and Pandan leaves (6.05 mg/kg) respectively. The heavy metal contents detected in all culinary herbs were below the permitted limits set by WHO/FAO, except Cd. The highest moisture (85.00±0.00%) and fiber (10.66± 2.00%) contents were found in Pandan leaves, while the highest protein (8.94±0.29%), fat (12.3± 2.52%) and ash (3.50± 0.17%) contents were reported in curry leaves. The information obtained from this study highlights the importance of further investigation of other antioxidant, antimicrobial and health promoting compounds of culinary herbs available in Sri Lanka for a detailed comparison.

Keywords: antimicrobial, antioxidant, culinary herbs, proximate analysis

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Authors: E. A. Amao, O. D. Amao, Z. O. Buzari, T. M. Adelegan, W. A. Tiamiyu, M. O. Yunus

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Signals from in vivo as well as in vitro studies shows that botanicals play notable roles in the treatment, prevention and management of diseases. Use of natural compounds in botanicals has been suggested as potential alternative to conventional therapeutic options. Therefore this study aimed to evaluate the effect of varying levels of turmeric powder (Curcuma longa) on semen characteristics and haematological indices of cocks. Turmeric (C. longa) was obtained from a local market in Saki in Oyo State, Nigeria, in March 2023. The rhizomes were washed, its skin scraped and air-dried for about 10 h, and further oven-dried at 40◦C for 12 h. afterwards, the dried turmeric was ground into powder using a blender. The product was kept in an air-tight container until the period of usage. The experimental material was drenched in cocks (60 cocks assigned into four treatments with three replicates) at 0.0g (T1), 0.05g (T2), 1.00g (T3) and 1.5g (T4) after 2 weeks of acclimatization. Semen volume, sperm cell progressive motility, sperm cell liveability, acrosome integrity, sperm cell concentration and normal sperm cell were evaluated for semen characteristics. Haematological parameters measured were: PCV, RBC, WBC Hb, MCV, MCH and MCHC. Data obtained were subjected to one-way analysis of variance. Semen volume (0.34 – 0.37ml), sperm cell progressive motility (68.33 – 80%), sperm cell liveability (46.66 – 85.00%), acrosome integrity (50.00 – 85%) and normal sperm cell (66.66 – 90%) shows significant difference (p<0.05) in favour cocks on higher level of turmeric powder. While sperm cell concentration (28.33 -40.00 X109/ml) shows no significant difference (p>0.05). PCV (36.00 – 40.33%), RBC (3.55 – 3.74 X106/ml), WBC (19.01 – 19.71 X109/ml), Hb (11.66 – 13.00 dl), MCV (100.53 – 109.53 ⴄ), MCH (32.57 – 35.31pg) and MCHC (32.00 – 32.37%) shows no significant difference (p>0.05). all serum biochemical indices showed significant difference (p<0.05) with animals on the test ingredient showed higher values in respect of the increase in turmeric powder.

Keywords: semen volume, total protein, packed cell volume, turmeric powder, albumin

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Authors: F. Clara Fang, Hernan Castaneda

Abstract:

The Connecticut Department of Transportation (ConnDOT) has constructed four roundabouts in the State of Connecticut within the past ten years. VISSIM traffic simulation software was utilized to analyze these roundabouts during their design phase. The queue length and level of service observed in the field appear to be better than predicted by the VISSIM model. The objectives of this project are to: identify VISSIM input variables most critical to accurate modeling; recommend VISSIM calibration factors; and, provide other recommendations for roundabout traffic operations modeling. Traffic data were collected at these roundabouts using Miovision Technologies. Cameras were set up to capture vehicle circulating activity and entry behavior for two weekdays. A large sample size of filed data was analyzed to achieve accurate and statistically significant results. The data extracted from the videos include: vehicle circulating speed; critical gap estimated by Maximum Likelihood Method; peak hour volume; follow-up headway; travel time; and, vehicle queue length. A VISSIM simulation of existing roundabouts was built to compare both queue length and travel time predicted from simulation with measured in the field. The research investigated a variety of simulation parameters as calibration factors for describing driver behaviors at roundabouts. Among them, critical gap is the most effective calibration variable in roundabout simulation. It has a significant impact to queue length, particularly when the volume is higher. The results will improve the design of future roundabouts in Connecticut and provide decision makers with insights on the relationship between various choices and future performance.

Keywords: driver critical gap, roundabout analysis, simulation, VISSIM modeling

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Authors: Adrien Cornille, Sylvain Caillol, Bernard Boutevon

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The development of polyurethanes began in 1937 at I. G. Farbenindustrie where Bayer with coworkers discovered the addition polymerization reaction between diisocyanates and diols. Since their discovery, the demand in PU has continued to increase and it will attain in 2016 a production of 18 million tons. However, isocyanates compounds are harmful to human and environment. Methylene diphenyl 4,4’-diisocyanate (MDI) and toluene diisocyanate (TDI), the most widely used isocyanates in PU industry, are classified as CMR (Carcinogen, Mutagen, and Reprotoxic). In order to design isocyanate-free materials, an interesting alternative is the use of Polyhydroxyurethanes (PHUs) by reaction between cyclic carbonate and polyfunctional amines. The main problem concerning PHUs synthesis relates to the low reactivity of carbonate/amine reaction. To solve this issue, many studies in the literature have been conducted to design PHU from more reactive cyclic-carbonates, bearing electro-withdrawing substituent or by using six-membered, seven-membered or thio-cyclic carbonate. The main drawback of all these systems remains the low molar masses obtained for the synthesized PHUs, which hinders their use for material applications. Therefore, we developed another strategy to afford new hybrid PHU with high conversion. This very innovative two-step approach consists in the first step in the synthesis of aminotelechelic PHU oligomers with different chain length from bis-cyclic carbonate with different excess of primary amine functions. In the second step, these aminotelechelic PHU oligomers were used in formulation with biobased epoxy monomers (from cashew nut shell liquid and tannins) to synthesize hybrid polyepoxyurethane polymers. These materials were then characterized by thermal and mechanical analyses.

Keywords: polyurethane, polyhydroxyurethane, aminotelechelic NIPU oligomers, carbonates, epoxy, amine, epoxyurethane polymers, hybrid polymers

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Authors: Rajwanlop Kumpoopong, Sukit Yindeesuk, Pornchai Silarom

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On May 5, 2014, an earthquake of magnitude 6.3 Richter hit the Northern part of Thailand. The epicenter was in Phan District, Chiang Rai Province. This earthquake or the so-called 2014-Chiang Rai Earthquake is the strongest ground shaking that Thailand has ever been experienced in her modern history. The 2014-Chiang Rai Earthquake confirms the geological evidence, which has previously been ignored by most engineers, that earthquakes of considerable magnitudes 6 to 7 Richter can occurr within the country. This promptly stimulates authorized agencies to pay more attention at the safety of their assets and promotes the comprehensive review of seismic resistance design of their building structures. The focus of this paper is to summarize the damages of highway bridges as a result of the 2014-Chiang Rai ground shaking, the remedy actions, and the research needs. The 2014-Chiang Rai Earthquake caused considerable damages to nearby structures such as houses, schools, and temples. The ground shaking, however, caused damage to only one highway bridge, Mae Laos Bridge, located several kilometers away from the epicenter. The damage of Mae Laos Bridge was in the form of concrete spalling caused by pounding of cap beam on the deck structure. The damage occurred only at the end or abutment span. The damage caused by pounding is not a surprise, but the pounding by only one bridge requires further investigation and discussion. Mae Laos Bridge is a river crossing bridge with relatively large approach structure. In as much, the approach structure is confined by strong retaining walls. This results in a rigid-like approach structure which vibrates at the acceleration approximately equal to the ground acceleration during the earthquake and exerts a huge force to the abutment causing the pounding of cap beam on the deck structure. Other bridges nearby have relatively small approach structures, and therefore have no capability to generate pounding. The effect of mass of the approach structure on pounding of cap beam on the deck structure is also evident by the damage of one pedestrian bridge in front of Thanthong Wittaya School located 50 meters from Mae Laos Bridge. The width of the approach stair of this bridge is wider than the typical one to accommodate the stream of students during pre- and post-school times. This results in a relatively large mass of the approach stair which in turn exerts a huge force to the pier causing pounding of cap beam on the deck structure during ground shaking. No sign of pounding was observed for a typical pedestrian bridge located at another end of Mae Laos Bridge. Although pounding of cap beam on the deck structure of the above mentioned bridges does not cause serious damage to bridge structure, this incident promotes the comprehensive review of seismic resistance design of highway bridges in Thailand. Given a proper mass and confinement of the approach structure, the pounding of cap beam on the deck structure can be easily excited even at the low to moderate ground shaking. In as much, if the ground shaking becomes stronger, the pounding is certainly more powerful. This may cause the deck structure to be unseated and fall off in the case of unrestrained bridge. For the bridge with restrainer between cap beam and the deck structure, the restrainer may prevent the deck structure from falling off. However, preventing free movement of the pier by the restrainer may damage the pier itself. Most highway bridges in Thailand have dowel bars embedded connecting cap beam and the deck structure. The purpose of the existence of dowel bars is, however, not intended for any seismic resistance. Their ability to prevent the deck structure from unseating and their effect on the potential damage of the pier should be evaluated. In response to this expected situation, Thailand Department of Highways (DOH) has set up a team to revise the standard practices for the seismic resistance design of highway bridges in Thailand. In addition, DOH has also funded the research project 'Seismic Resistance Evaluation of Pre- and Post-Design Modifications of DOH’s Bridges' with the scope of full-scale tests of single span bridges under reversed cyclic static loadings for both longitudinal and transverse directions and computer simulations to evaluate the seismic performance of the existing bridges and the design modification bridges. The research is expected to start in October, 2015.

Keywords: earthquake, highway bridge, Thailand, damage, pounding, seismic resistance

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Authors: Okan Cakir, Okan Tatli

Abstract:

Acute motor and sensory axonal neuropathy (AMSAN) syndrome usually occurs following a postviral infection in two to four weeks and is a polyneuropathy characterized by axonal and sensorial degeneration as a rare variant of Gullian-Barre syndrome. In our case, we wanted to mention that a rare case of AMSAN Syndrome due to prior surgery. A 61-year-old male case admitted to emergency department with complaints of weakness in feet, numbness and incapability to walk. In his history, it was learned that endovascular aneurysm repair (EVAR) had applied for abdominal aort aneurysm two weeks ago before admission, his complaints had been for a couple of days increasingly and bilaterally, and there had been no infection disease history for four weeks. In physical examination, general status was good, vital signs were stable, and there was a mild paresis in dorsal flexion of feet in bilaterally lower extremities. No nuchal rigidity was determined. Other system examinations were normal. Urea:52 mg/dL (normal range: 15-44 mg/dL), creatinine: 1,05 mg/dL (normal range: 0,81-1,4 mg/dL), potassium: 3,68 mmol/L (normal range: 3,5-5,5 mmol/L), glycaemia: 142 mg/dL, calcium: 9,71 mg/dL (normal range: 8,5-10,5 mg/dL), erythrocyte sedimentation rate (ESR): 74 mm/h (normal range: 0-15 mm/h) were determined in biochemical tests. The case was consulted to neurology department and hospitalized. In performing electromyography, it was reported as a bilateral significant axonal degeneration with sensory-motor polyneuropathy. Normal ranges of glycaemia and protein levels were detected in lumbal punction. Viral markers and bucella, toxoplasma, and rubella markers were in normal range. Intravenous immunoglobulin (IVIG) was applied as a treatment, physical treatment programme was planned and the case discharged from neurology department. In our case, we mentioned that it should be considered polyneuropathy as an alternative diagnosis in cases admitting symptoms like weakness and numbness had a history of prior surgery.

Keywords: AMSAN Syndrome, emergency department, prior surgery, weakness

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Authors: Mauricio Cruz, Andrés Díaz García, Martha Isabel Gómez, Juan Carlos Serrato Bermúdez

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The disadvantages of using natural substrates in SSF processes have been well recognized and mainly are associated to gradual decomposition of the substrate, formation of agglomerates and decrease of porosity bed generating limitations in the mass and heat transfer. Additionally, in several cases, materials with a high agricultural value such as sour milk, beets, rice, beans and corn have been used. Thus, the use of economic inert supports (natural or synthetic) in combination with a nutrient suspension for the production of biocontrol microorganisms is a good alternative in SSF processes, but requires further studies in the fields of modeling and optimization. Therefore, the aim of this work is to compare the performance of two inert supports, a synthetic (polyurethane foam) and a natural one (rice husk), identifying the factors that have the major effects on the productivity of T. asperellum Th204 and the maximum specific growth rate in a PROPHYTA L05® fixed bed bioreactor. For this, the six factors C:N ratio, temperature, inoculation rate, bed height, air moisture content and airflow were evaluated using a fractional design. The factors C:N and air flow were identified as significant on the productivity (expressed as conidia/dry substrate•h). The polyurethane foam showed higher maximum specific growth rate (0.1631 h-1) and productivities of 3.89 x107 conidia/dry substrate•h compared to rice husk (2.83x106) and natural substrate based on rice (8.87x106) used as control. Finally, a quadratic model was generated and validated, obtaining productivities higher than 3.0x107 conidia/dry substrate•h with air flow at 0.9 m3/h and C:N ratio at 18.1.

Keywords: bioprocess, scale up, fractional design, C:N ratio, air flow

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Authors: Magdalena Rusady Goey, Gordon Strathdee, Neil Perkins

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Background: Acute lymphoblastic leukaemia (ALL) is the most frequent type of childhood malignancy, accounting for 25% of all cases. TWIST2, a basic helix-loop-helix transcription factor, has been implicated in ALL development. Prior studies found that TWIST2 undergoes epigenetic silencing in more than 50% cases of ALL through promoter hypermethylation and suggested that re-expression of TWIST2 may inhibit cell growth/survival of leukaemia cell lines. TWIST2 has also been implicated as a regulator of NF-kappaB activity, which is constitutively active in leukaemia. Here, we use a lentiviral transductions system to confirm the importance of TWIST2 in controlling leukaemia cell growth and to investigate whether this is achieved through altered regulation of NF-kappaB activity. Method: Re-expression of TWIST2 in leukaemia cell lines was achieved using lentiviral-based transduction. The lentiviral vector also expresses enhanced green fluorescent protein (eGFP), allowing transduced cells to be tracked using flow cytometry. Analysis of apoptosis and cell proliferation were done using annexinV and VPD450 staining, respectively. Result and Discussion: TWIST2-expressing cells were rapidly depleted from a mixed population in ALL cell lines (NALM6 and Reh), indicating that TWIST2 inhibited cell growth/survival of ALL cells. In contrast, myeloid cell lines (HL60 and K562) were comparatively insensitive to TWIST2 re-expression. Analysis of apoptosis and cell proliferation found no significant induction of apoptosis, but did find a rapid induction of proliferation arrest in TWIST2-expressing Reh and NALM6 cells. Initial experiment with NF-kappaB inhibitor demonstrated that inhibition of NF-kappaB has similar impact on cell proliferation in the ALL cell lines, suggesting that TWITST2 may induce cell proliferation arrest through inhibition of NF-kappaB. Conclusion: The results of this study suggest that epigenetic inactivation of TWIST2 in primary ALL leads to increased proliferation, potentially by altering the regulation of NF-kappaB.

Keywords: leukaemia, acute lymphoblastic leukaemia, NF-kappaB, TWIST2, lentivirus

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Authors: Victor William Harris

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Objective. This study examined the impact of the Positive Behavioral Management Skills (PBMS) online educational program on participants (n = 624) in a Southeastern region of the United States. The PBMS program incorporates established positive psychology behavioral management principles with new research-based practices designed to promote healthy and satisfying relationships between adults and children while constructively managing and preventing problematic behavior. Additionally, the PBMS program assists parents and teachers in recognizing the motivations behind a wide range of misbehaviors. The program also offers to forewarn some of the most common mistakes (or “parent traps”) in child behavioral management and describes how they can be avoided. It also describes how to recognize and capitalize on “teachable moments,” which are indispensable in the developmental process. Design. A retrospective-pre-test-then-post-test design was used to reduce response shift bias when assessing knowledge and skill intervention outcomes for twenty-two behavioral management variables. Results. The PBMS program was shown to be effective for increasing knowledge and skills related to managing misbehavior while reinforcing interpersonal relationships and fostering a sense of responsibility and capability within the child. Large standardized mean effect size changes from before to after program intervention was documented for PBMS participants on all twenty-two variables studied. Conclusion. The PBMS program showed initial positive outcomes to assist participants in the sample studied to increase their knowledge and skills in managing child behavior successfully. Implications for parents, educators and practitioners are discussed.

Keywords: behavioral management, discipline, parent education, positive parenting, positive psychology-parenting

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Authors: Ayub Khan, Net Ram Garg, Geeta Jain

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In this paper, backstepping method is proposed to synchronize two fractional-order systems. The simulation results show that this method can effectively synchronize two chaotic systems.

Keywords: backstepping method, fractional order, synchronization, chaotic system

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Authors: Ali Bayram, Remzi Yiğiter

Abstract:

Objective: Alzheimer's disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease. At present, diagnosis of AD is rather late in the disease. Therefore, we attempted to find peripheral biomarkers for the early diagnosis of AD. Herein, we conducted a study to investigate the unc-51 like autophagy activating kinase-1 (ULK1) mRNA expression levels in human peripheral blood mononuclear cells from patients with Alzheimer's disease. Method: To determine whether ULK1 gene expression are altered in AD patients, we measured their gene expression in human peripheral blood cell in 50 patients with AD and 50 age and gender matched healthy controls by quantitative real-time PCR technique. Results: We found that both ULK1 gene expression in peripheral blood cell were significantly decreased in patients with AD as compared with controls (p <0.05). Lower levels of ULK1 gene expression were significantly associated with the increased risk for AD. Conclusions: Serine/threonine-protein kinase involved in autophagy in response to starvation. Acts upstream of phosphatidylinositol 3-kinase PIK3C3 to regulate the formation of autophagophores, the precursors of autophagosomes. Part of regulatory feedback loops in autophagy: acts both as a downstream effector and negative regulator of mammalian target of rapamycin complex 1 (mTORC1) via interaction with RPTOR. Activated via phosphorylation by AMPK and also acts as a regulator of AMPK by mediating phosphorylation of AMPK subunits PRKAA1, PRKAB2, and PRKAG1, leading to negatively regulate AMPK activity. May phosphorylate ATG13/KIAA0652 and RPTOR; however such data need additional evidences. Plays a role early in neuronal differentiation and is required for granule cell axon formation. Alzheimer is the most common neurodegenerative disease. Our results provide useful information that the ULK1 gene expression is decreased in the neurodegeneration and AD patients with, indicating their possible systemic involvement in AD.

Keywords: Alzheimer’s sisease, ULK1, mRNA expression, RT-PCR

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Authors: Reihane Mehrparvar

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Human age could exceed further by altering gene expression through food intaking, although as a consequence of recent century eating patterns, human life-span getting shorter by emerging irregulating in autophagy mechanism, insulin, leptin, gut microbiota which are important etiological factors of type-2 diabetes, obesity, infertility, cancer, metabolic and autoimmune diseases. However, restricted calorie intake and vigorous exercise might be beneficial for losing weight and metabolic regulation in a short period but could not be implementable in the long term as a way of life. Therefore, the lack of a dietary program that is compatible with the genes of the body is essential. Sweet and high-glycemic-index (HGI) foods were associated with type-2 diabetes and cancer morbidity. The neuropsychological perspective characterizes the inclination of sweet and HGI-food consumption as addictive behavior; hence this process engages preference of gut microbiota, neural node, and dopaminergic functions. Moreover, meal composition is not the only factor that affects body hemostasis. In this narrative review, it is believed to attempt to investigate how the body responded to different food intakes and represent an accurate model based on current evidence. Eating frequently and ingesting unassimilable protein and carbohydrates may not be compatible with human genes and could cause impairments in the self-renovation mechanism. This trajectory indicates our body is more adapted to starvation and eating animal meat and marrow. Here has been recommended a model that takes into account three important factors: frequent eating, meal composition, and circadian rhythm, which may offer a promising intervention for obesity, inflammation, cardiovascular, autoimmune disorder, type-2 diabetes, insulin resistance, infertility, and cancer through intensifying autophagy-mechanism and eliminate medical costs.

Keywords: metabolic disease, anti-aging, type-2 diabetes, autophagy

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