Search results for: high protein and energy diet

Authors: A. Y. Tsidulko, T. M. Pankova, E. V. Grigorieva

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High-grade gliomas are the most frequent and most aggressive brain tumors which are characterized by active invasion of tumor cells into the surrounding brain tissue, where the extracellular matrix (ECM) plays a crucial role. Disruption of ECM can be involved in anticancer drugs effectiveness, side-effects and also in tumor relapses. The anti-inflammatory agent dexamethasone is a common drug used during high-grade glioma treatment for alleviating cerebral edema. Although dexamethasone is widely used in the clinic, its effects on normal brain tissue ECM remain poorly investigated. It is known that proteoglycans (PGs) are a major component of the extracellular matrix in the central nervous system. In our work, we studied the effects of dexamethasone on the ECM proteoglycans (syndecan-1, glypican-1, perlecan, versican, brevican, NG2, decorin, biglican, lumican) using RT-PCR in the experimental animal model. It was shown that proteoglycans in rat brain have age-specific expression patterns. In early post-natal rat brain (8 days old rat pups) overall PGs expression was quite high and mainly expressed PGs were biglycan, decorin, and syndecan-1. The overall transcriptional activity of PGs in adult rat brain is 1.5-fold decreased compared to post-natal brain. The expression pattern was changed as well with biglycan, decorin, syndecan-1, glypican-1 and brevican becoming almost equally expressed. PGs expression patterns create a specific tissue microenvironment that differs in developing and adult brain. Dexamethasone regimen close to the one used in the clinic during high-grade glioma treatment significantly affects proteoglycans expression. It was shown that overall PGs transcription activity is 1.5-2-folds increased after dexamethasone treatment. The most up-regulated PGs were biglycan, decorin, and lumican. The PGs expression pattern in adult brain changed after treatment becoming quite close to the expression pattern in developing brain. It is known that microenvironment in developing tissues promotes cells proliferation while in adult tissues proliferation is usually suppressed. The changes occurring in the adult brain after dexamethasone treatment may lead to re-activation of cell proliferation due to signals from changed microenvironment. Taken together obtained data show that dexamethasone treatment significantly affects the normal brain ECM, creating the appropriate microenvironment for tumor cells proliferation and thus can reduce the effectiveness of anticancer treatment and promote tumor relapses. This work has been supported by a Russian Science Foundation (RSF Grant 16-15-10243)

Keywords: dexamthasone, extracellular matrix, glioma, proteoglycan

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Authors: Minho Kwak, Suhwan Yun, Choonsoo Park

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Nose shape optimizations of high-speed train are performed for the improvement of aerodynamic characteristics. Based on the commercial train, KTX-Sancheon, multi-objective optimizations are conducted for the improvement of the side wind stability and the micro-pressure wave following the optimization for the reduction of aerodynamic drag. 3D nose shapes are modelled by the Vehicle Modeling Function. Aerodynamic drag and side wind stability are calculated by three-dimensional compressible Navier-Stokes solver, and micro pressure wave is done by axi-symmetric compressible Navier-Stokes solver. The Maxi-min Latin Hypercube Sampling method is used to extract sampling points to construct the approximation model. The kriging model is constructed for the approximation model and the NSGA-II algorithm was used as the multi-objective optimization algorithm. Nose length, nose tip height, and lower surface curvature are design variables. Because nose length is a dominant variable for aerodynamic characteristics of train nose, two optimization processes are progressed respectively with and without the design variable, nose length. Each pareto set was obtained and each optimized nose shape is selected respectively considering Honam high-speed rail line infrastructure in South Korea. Through the optimization process with the nose length, when compared to KTX Sancheon, aerodynamic drag was reduced by 9.0%, side wind stability was improved by 4.5%, micro-pressure wave was reduced by 5.4% whereas aerodynamic drag by 7.3%, side wind stability by 3.9%, micro-pressure wave by 3.9%, without the nose length. As a result of comparison between two optimized shapes, similar shapes are extracted other than the effect of nose length.

Keywords: aerodynamic characteristics, design variable, multi-objective optimization, train nose shape

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Authors: Tamás Hartványi, Ferenc Tóth

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European telecommunication distribution center performance is measured by service lead time and quality. Operation model is CTO (customized to order) namely, a high mix customization of telecommunication network equipment and parts. CTO operation contains material receiving, warehousing, network and server assembly to order and configure based on customer specifications. Variety of the product and orders does not support mass production structure. One of the success factors to satisfy customer is to have a proper aggregated planning method for the operation in order to have optimized human resources and highly efficient asset utilization. Research will investigate several methods and find proper way to have an order book simulation where practical optimization problem may contain thousands of variables and the simulation running times of developed algorithms were taken into account with high importance. There are two operation research models that were developed, customer demand is given in orders, no change over time, customer demands are given for product types, and changeover time is constant.

Keywords: CTO, aggregated planning, demand simulation, changeover time

Procedia PDF Downloads 254

Authors: Ahmad Abu-Akel, Emilie De Montpellier, Sophie Von Bentivegni, Lyn Luechinger, Alessandro Ishii, Christine Mohr

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Convergent and divergent thinking are two main components of creativity that have been viewed as complementary. While divergent thinking refers to the fluency and flexibility of generating new ideas, convergent thinking refers to the ability to systematically apply rules and knowledge to arrive at the optimal solution or idea. These creativity components have been shown to be susceptible to variation in subclinical expressions of autistic and schizotypal traits within the general population. Research, albeit inconclusively, mainly linked positive schizotypal traits with divergent thinking and autistic traits with convergent thinking. However, cumulative evidence suggests that these trait dimensions can co-occur in the same individual more than would be expected by chance and that their concurrent effect can be diametric and even interactive. The current study aimed at investigating the concurrent effect of these trait dimensions on tasks assessing convergent and divergent thinking abilities. We predicted that individuals with high positive schizotypal traits alone would perform particularly well on the divergent thinking task, whilst those with high autistic traits alone would perform particularly well on the convergent thinking task. Crucially, we also predicted that individuals who are high on both autistic and positive schizotypal traits would perform particularly well on both the divergent and convergent thinking tasks. This was investigated in a non-clinical sample of 142 individuals (Males = 45%; Mean age = 21.45, SD = 2.30), sufficient to minimally observe an effect size f² ≥ .10. Divergent thinking was evaluated using the Alternative Uses Task, and convergent thinking with the Anagrams Task. Autistic and schizotypal traits were respectively assessed with the Autism Quotient Questionnaire (AQ) and the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE). Regression analyses revealed that the positive association of autistic traits with convergent thinking scores was qualified with an interaction with positive schizotypal traits. Specifically, positive schizotypal traits were negatively associated with convergent thinking scores when AQ scores were relatively low, but this trend was reversed when AQ scores were high. Conversely, the positive effect of AQ scores on convergent thinking progressively increased with increasing positive schizotypal traits. The results of divergent thinking task are currently being analyzed and will be reported at the conference. The association of elevated autistic and positive schizotypal traits with convergent thinking may represent a unique profile of creative thinkers who are able to simultaneously draw on trait-specific advantages conferred by autistic and positively schizotypal traits such as local and global processing. This suggests that main-effect models can tell an incomplete story regarding the effect of autistic and positive schizotypal traits on creativity-related processes. Future creativity research should consider their interaction and the benefits conferred by their co-presence.

Keywords: autism, schizotypy, convergent thinking, divergent thinking, comorbidity

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Authors: Rukia Yosuf

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Diabetes is a national healthcare crisis related to both macrovascular and microvascular complications. We hypothesized that higher levels of physical activity are associated with lower total and visceral fat mass, lower systolic blood pressure, and increased insulin sensitivity. Participant inclusion criteria: 21-50 years old, BMI ≥ 30 kg/m2, hemoglobin A1C 5.7-6.4, fasting glucose 100-125 mg/dL, and HOMA IR ≥ 2.5. Exclusion criteria: history of diabetes, hypertension, HIV, renal disease, hearing loss, alcoholic intake over four drinks daily, use of organic nitrates or PDE5 inhibitors, and decreased cardiac function. Total physical activity was measured using accelerometers, body composition using DXA, and insulin resistance via fsIVGTT. Clinical and biochemical cardiometabolic risk factors, blood pressure and heart rate were obtained using a calibrated sphygmomanometer. Anthropometric measures, fasting glucose, insulin, lipid profile, C-reactive protein, and BMP were analyzed using standard procedures. Within our study, we found correlations between levels of physical activity in a heterogeneous group of prediabetic adults. Patients with more physical activity had a higher degree of insulin sensitivity, lower blood pressure, total visceral adipose tissue, and overall lower total mass. Total physical activity levels showed small, but significant correlations with systolic blood pressure, visceral fat, lean mass and insulin sensitivity. After normalizing for the race, age, and gender using multiple regression, these associations were no longer significant considering our small sample size. More research into prediabetes will decrease the population of diabetics overall. In the future, we could increase sample size and conduct cross sectional and longitudinal studies in various populations with prediabetes.

Keywords: diabetes, kidney disease, nephrology, prediabetes

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Authors: Aline Giardin, Maria Rosa Chitolina, Maria Catarina Zanini

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In this paper, we analyze the conceptions of high school students about mental health issues, and discuss the creation of mental basic health programs in schools. We base our findings in a quantitative survey carried out by us with 156 high school students of CTISM (Colégio Técnico Industrial de Santa Maria) school, located in Santa Maria city, Brazil. We have found that: (a) 28 students relate the subject ‘mental health’ with psychiatric hospitals and lunatic asylums; (b) 28 students have relatives affected by mental diseases; (c) 76 students believe that mental patients, if treated, can live a healthy life; (d) depression, schizophrenia and bipolar disorder are the most cited diseases; (e) 84 students have contact with mental patients, but know nothing about the disease; (f) 123 students have never been instructed about mental diseases while in the school; and (g) 135 students think that a mental health program would be important in the school. We argue that these numbers reflect a vision of mental health that can be related to the reductionist education still present in schools and to the lack of integration between health professionals, sciences teachers, and students. Furthermore, this vision can also be related to a stigmatization process, which interferes with the interactions and with the representations regarding mental disorders and mental patients in society.

Keywords: mental health, schools, mental illness, conception

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Authors: Benoît Mary, Thibaut Gras, Gaëtan Fagot, Yvon Goth, Ilyes Mnassri-Cetim

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A Gerotor pump is composed of an external and internal gear with conjugate cycloidal profiles. From suction to delivery ports, the fluid is transported inside cavities formed by teeth and driven by the shaft. From a geometric and conceptional side it is worth to note that the internal gear has one tooth less than the external one. Simcenter Amesim v.16 includes a new submodel for modelling the hydraulic Gerotor pumps behavior (THCDGP0). This submodel considers leakages between teeth tips using Poiseuille and Couette flows contributions. From the 3D CAD model of the studied pump, the “CAD import” tool takes out the main geometrical characteristics and the submodel THCDGP0 computes the evolution of each cavity volume and their relative position according to the suction or delivery areas. This module, based on international publications, presents robust results up to 6 000 rpm for pressure greater than atmospheric level. For higher rotational speeds or lower pressures, oil aeration and cavitation effects are significant and highly drop the pump’s performance. The liquid used in hydraulic systems always contains some gas, which is dissolved in the liquid at high pressure and tends to be released in a free form (i.e. undissolved as bubbles) when pressure drops. In addition to gas release and dissolution, the liquid itself may vaporize due to cavitation. To model the relative density of the equivalent fluid, modified Henry’s law is applied in Simcenter Amesim v.16 to predict the fraction of undissolved gas or vapor. Three parietal pressure sensors have been set up upstream from the pump to estimate the sound speed in the oil. Analytical models have been compared with the experimental sound speed to estimate the occluded gas content. Simcenter Amesim v.16 model was supplied by these previous analyses marks which have successfully improved the simulations results up to 14 000 rpm. This work provides a sound foundation for designing the next Gerotor pump generation reaching high rotation range more than 25 000 rpm. This improved module results will be compared to tests on this new pump demonstrator.

Keywords: gerotor pump, high speed, numerical simulations, aeronautic, aeration, cavitation

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Authors: Li Qingjian, Li Ke, He Chun, Huang Yong

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In this paper, the method of combining the Pohl Seidman's deep belief network with the self-organizing neural network is proposed to classify the target. This method is mainly aimed at the high nonlinearity of the hyperspectral image, the high sample dimension and the difficulty in designing the classifier. The main feature of original data is extracted by deep belief network. In the process of extracting features, adding known labels samples to fine tune the network, enriching the main characteristics. Then, the extracted feature vectors are classified into the self-organizing neural network. This method can effectively reduce the dimensions of data in the spectrum dimension in the preservation of large amounts of raw data information, to solve the traditional clustering and the long training time when labeled samples less deep learning algorithm for training problems, improve the classification accuracy and robustness. Through the data simulation, the results show that the proposed network structure can get a higher classification precision in the case of a small number of known label samples.

Keywords: DBN, SOM, pattern classification, hyperspectral, data compression

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Authors: Emilio A. Berny-Brandt, Sonia E. Ruiz

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Steel tubular towers serving as support structures for large wind turbines are subject to several hundred million stress cycles arising from the turbulent nature of the wind. This causes high-cycle fatigue which can govern tower design. The practice of maintaining the support structure after wind turbines reach its typical 20-year design life have become common, but without quantifying the changes in the reliability on the tower. There are several studies on this topic, but most of them are based on the S-N curve approach using the Miner’s rule damage summation method, the de-facto standard in the wind industry. However, the qualitative nature of Miner’s method makes desirable the use of fracture mechanics to measure the effects of fatigue in the capacity curve of the structure, which is important in order to evaluate the integrity and reliability of these towers. Temporal and spatially varying wind speed time histories are simulated based on power spectral density and coherence functions. Simulations are then applied to a SAP2000 finite element model and step-by-step analysis is used to obtain the stress time histories for a range of representative wind speeds expected during service conditions of the wind turbine. Rainflow method is then used to obtain cycle and stress range information of each of these time histories and a statistical analysis is performed to obtain the distribution parameters of each variable. Monte Carlo simulation is used here to evaluate crack growth over time in the tower base using the Paris-Erdogan equation. A nonlinear static pushover analysis to assess the capacity curve of the structure after a number of years is performed. The capacity curves are then used to evaluate the changes in reliability of a steel tower located in Oaxaca, Mexico, where wind energy facilities are expected to grow in the near future. Results show that fatigue on the tower base can have significant effects on the structural capacity of the wind turbine, especially after the 20-year design life when the crack growth curve starts behaving exponentially.

Keywords: crack growth, fatigue, Monte Carlo simulation, structural reliability, wind turbines

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Authors: Mehmet Akköse

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Concern about seismic safety of concrete dams have been growing around the world, partly because the population at risk in locations downstream of major dams continues to expand and also because it is increasingly evident that the seismic design concepts in use at the time most existing dams were built were inadequate. Most of the investigations in the past have been conducted on large dams, typically above 100m high. A large number of concrete dams in our country and in other parts of the world are less than 50m high. Most of these dams were usually designed using pseudo-static methods, ignoring the dynamic characteristics of the structure as well as the characteristics of the ground motion. Therefore, it is important to carry out investigations on seismic behavior this category of dam in order to assess and evaluate the safety of existing dams and improve the knowledge for different high dams to be constructed in the future. In this study, size effects on structural performance of concrete gravity dams subjected to near and far-fault ground motions are investigated including dam-water-foundation interaction. For this purpose, a benchmark problem proposed by ICOLD (International Committee on Large Dams) is chosen as a numerical application. Structural performance of the dam having five different heights is evaluated according to damage criterions in USACE (U.S. Army Corps of Engineers). It is decided according to their structural performance if non-linear analysis of the dams requires or not. The linear elastic dynamic analyses of the dams to near and far-fault ground motions are performed using the step-by-step integration technique. The integration time step is 0.0025 sec. The Rayleigh damping constants are calculated assuming 5% damping ratio. The program NONSAP modified for fluid-structure systems with the Lagrangian fluid finite element is employed in the response calculations.

Keywords: concrete gravity dams, Lagrangian approach, near and far-fault ground motion, USACE damage criterions

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Authors: Goodarzvand Fatemeh, Soori Rahman, Effatpanah Mohammad, Ajbarnejad Ali

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Attention deficit hyperactivity disorder (ADHD) is characterized by a pervasive pattern of developmentally inappropriate inattentive, impulsive and hyperactive behaviors that typically begin during the preschool ages and often persist into adulthood. This disorder is related to autism and schizophrenia and other psychological disorders and clinical conditions such as insulin resistance and they may operate through common pathways, and treatments used exclusively for one of these conditions may prove beneficial for the others. While ADHD is not fully understood as developmental disorder with an etiopathogeny, but studies show that core symptom of disorder was associated with and increased by the interleukins IL-13, where relation of IL-13 with inattention was notable. Regular exercise improves functions associated with attention deficit hyperactivity disorder (ADHD). However, the impact of exercise on cytokines associated with the disease activity remains relatively unexplored. The aim of this study was to examine the effects of 6 weeks high intensity by intervals training (HIIT) on IL-13 levels and insulin resistance in boys with ADHD. Twenty eight boys with ADHD disease in a range of 12-18 year of old participated in this study as the subject. Subjects were divided into control group (n=10) and training group (n=18) randomly. The training group performed progressive HIIT program, 3 days a week for 6 weeks. The control group was in absolute rest at the same time. The results showed that after six weeks of HIIT, IL-13 decreased in the exercise group and these changes achieved (p= 0.002) statistical significance (p < 0.005). The results suggest HIIT with specific intensity and duration utilized in this study had not significant effect on insulin resistance levels in female patients with ADHD (p=0.39), while the difference in the average control and case group was decreased.

Keywords: attention deficit hyperactivity disorder, interleukin 13, insulin resistance, high intensity by intervals training

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Authors: L. Pu, C. Unluer

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MgO cements have the potential to sequester CO2 in construction products, and can be partial or complete replacement of PC in concrete. Construction block is a promising application for reactive MgO cements. Main advantages of blocks are: (i) suitability for sequestering CO2 due to their initially porous structure; (ii) lack of need for in-situ treatment as carbonation can take place during fabrication; and (iii) high potential for commercialization. Both strength gain and carbon sequestration of MgO cements depend on carbonation process. Fly ash and ground granulated blast-furnace slag (GGBS) are pozzolanic material and are proved to improve many of the performance characteristics of the concrete, such as strength, workability, permeability, durability and corrosion resistance. A very limited amount of work has been reported on the production of MgO blocks on a large scale so far. A much more extensive study, wherein blocks with different mix design is needed to verify the feasibility of commercial production. The changes in the performance of the samples were evaluated by compressive strength testing. The properties of the carbonation products were identified by X-ray diffraction (XRD) and scanning electron microscopy (SEM)/ field emission scanning electron microscopy (FESEM), and the degree of carbonation was obtained by thermogravimetric analysis (TGA), XRD and energy dispersive X-ray (EDX). The results of this study enabled the understanding the relationship between lab-scale samples and scale-up blocks based on their mechanical performance and microstructure. Results indicate that for both scaled-up and lab-scale samples, MgO samples always had the highest strength results, followed by MgO-fly ash samples and MgO-GGBS had relatively lowest strength. The lower strength of MgO with fly ash/GGBS samples at early stage is related to the relatively slow hydration process of pozzolanic materials. Lab-scale cubic samples were observed to have higher strength results than scaled-up samples. The large size of the scaled-up samples made it more difficult to let CO2 to reach inner part of the samples and less carbonation products formed. XRD, TGA and FESEM/EDX results indicate the existence of brucite and HMCs in MgO samples, M-S-H, hydrotalcite in the MgO-fly ash samples and C-S-H, hydrotalctie in the MgO-GGBS samples. Formation of hydration products (M-S-H, C-S-H, hydrotalcite) and carbonation products (hydromagnecite, dypingite) increased with curing duration, which is the reason of increasing strength. This study verifies the advantage of large-scale MgO blocks over common PC blocks and the feasibility of commercial production of MgO blocks.

Keywords: reactive MgO, fly ash, ground granulated blast-furnace slag, carbonation, CO₂

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Authors: Azieva A. M., Yastremsky E. V., Kirillova D. A., Patsaev T. D., Sharikov R. V., Kamyshinsky R. A., Lukanina K. I., Sharikova N. A., Grigoriev T. E., Vasiliev A. L.

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Adhesive properties of scaffolds, which predominantly depend on the chemical and structural features of their surface, play the most important role in tissue engineering. The basic requirements for such scaffolds are biocompatibility, biodegradation, high cell adhesion, which promotes cell proliferation and differentiation. In many cases, synthetic polymers scaffolds have proven advantageous because they are easy to shape, they are tough, and they have high tensile properties. The regeneration of nerve tissue still remains a big challenge for medicine, and neural stem cells provide promising therapeutic potential for cell replacement therapy. However, experiments with stem cells have their limitations, such as low level of cell viability and poor control of cell differentiation. Whereas the study of already differentiated neuronal cell culture obtained from newborn mouse brain is limited only to cell adhesion. The growth and implantation of neuronal culture requires proper scaffolds. Moreover, the polymer scaffolds implants with neuronal cells could demand specific morphology. To date, it has been proposed to use numerous synthetic polymers for these purposes, including polystyrene, polylactic acid (PLA), polyglycolic acid, and polylactide-glycolic acid. Tissue regeneration experiments demonstrated good biocompatibility of PLA scaffolds, despite the hydrophobic nature of the compound. Problem with poor wettability of the PLA scaffold surface could be overcome in several ways: the surface can be pre-treated by poly-D-lysine or polyethyleneimine peptides; roughness and hydrophilicity of PLA surface could be increased by plasma treatment, or PLA could be combined with natural fibers, such as collagen or chitosan. This work presents a study of adhesion of both induced pluripotent stem cells (iPSCs) and mouse primary neuronal cell culture on the polylactide scaffolds of various types: oriented and non-oriented fibrous nonwoven materials and sponges – with and without the effect of plasma treatment and composites with collagen and chitosan. To evaluate the effect of different types of PLA scaffolds on the neuronal differentiation of iPSCs, we assess the expression of NeuN in differentiated cells through immunostaining. iPSCs more effectively differentiate into neurons on PLA scaffolds with high adhesive properties for primary neuronal cells.

Keywords: PLA scaffold, neurons, neuronal differentiation, stem cells, polylactid

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Authors: Jitendra Sharma

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Here a Homogeneous Charge is used as in a spark-ignited engine, but the charge is compressed to auto ignition as in a diesel. The main difference compared with the Spark Ignition (SI) engine is the lack of flame propagation and hence the independence from turbulence. Compared with the diesel engine. HCCI has a homogeneous charge and have no problems associated with soot and Nox but HC and CO were higher than in SI mode. It was not possible to achieve high IMEP (Indicated Mean Effective Pressure) values with HCCI. The Homogeneous charge compression ignition (HCCI) is an attractive technology because of its high efficiency and low emissions. However, HCCI lakes a direct combustion trigger making control of combustion timing challenging, especially during transients. To aid in HCCI engine control we present a simple model of the HCCI combustion process valid over a range of intake pressures, intake temperatures, equivalence ratios and engine speeds. HCCI a new combustion technology that may develop as an alternative to diesel engines with high efficiency and low Knox and particulate matter emissions. The homogenous charge compression ignition (HCCI) is a promising new engine technology that combines elements of the diesel and gasoline engine operating cycles. HCCI as a way to increase the efficiency of the gasoline engine. The attractive properties are increased fuel efficiency due to reduced throttling losses, increased expansion ratio and higher thermodynamic efficiency. With the advantages there are some mechanical limitations to the operation of the HCCI engine. The implementation of homogenous charge compression ignition (HCCI) to gasoline engines is constrained by many factors. The main drawback of HCCI is the absence of direct combustion timing control. Therefore all the right conditions for auto ignition have to be set before combustion starts. This paper describes the past and current research done on HCCI engine. Many research got considerable success in doing detailed modeling of HCCI combustion. This paper aims at studying the fundamentals of HCCI combustion, the strategy to control the limitation of HCCI engine.

Keywords: HCCI, diesel engine, combustion, elementary investigation

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Authors: Sergio Luiz da Costa Junior, Carolina Fofonka Palomino, Paulo Cesar Lodi

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The use of light landfills is an effective solution for road works in soft ground sites, such as Rio de Janeiro (RJ) and Santos (SP) - the Southeastern Brazilian coast. The technique consists in replacing the topsoil by expandable polystyrene (EPS) geofoam, lined with geomembrane to prevent the attack of chemical products.Thus, knowing the interface shear strength of those materials is important in projects to avoid rupturing the system. The purpose of this paper is to compare the shear strength in the geomembrane-EPS interfaces by the direct shear test. The tests were performed under the dry and saturated condition, and four kind of high-density polyethylene (HDPE) 2,00mm geomembranes were used, smooth and texturized - manufactured in the flat die and blown film process. It was found that the shear strength is directly influenced by the roughness of the geomembrane, showed higher friction angle in the textured geomembrane. The direct shear test, in the saturated condition, also showed smaller friction angle than the now-wetted test.

Keywords: geofoam, geomembrane, soft ground, strength shear

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Authors: Wei-Ju Huang, Hung-Pin Hsu

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[Background] In congestive heart failure (CHF), it has always been the principle of clinical treatment to control the water retention mechanism in the body to prevent excessive fluid retention. Early control of sympathetic nerves, Renin-Angiotensin-Aldosterone system (RAA system, RAAS), or strengthening of Atrial Natriuretic Peptide (ANP) was the point. In RAA system, related hormones, such as angiotensin, or enzymes in the pathway, such as ACE-I, can be used with corresponding inhibitors to reduce water content.[Aim] In recent years, clinical studies have pointed out that if different mechanisms are combined, the control effect seems to be better. For example, recent studies showed that ENTRESTO, a combination of Sacubitril and Valsartan, is a good new drug for CHF. Sacubitril is a prodrug. After activation, it can inhibit neprilysin and act as a neprilysin inhibitor (ARNI) to reduce the breakdown of natriuretic peptides(ANP). Valsartan is a kind of angiotensin receptor blocker (ARB), both of which are used to treat heart failure at the same time, have excellent curative effects.[Materials and Methods] Considering the side effects of this drug, coughing and a few cases of diarrhea were observed. However, the effect of this drug on the patient's intestinal tract has not been confirmed. On the other hand, studies have pointed out that ANP supplement can improve the CHF and increase the inhibitory effect on cancer cells. Therefore, the purpose of this study is to use a special microbial detection method to prove that whether oral drugs have an effect on microorganisms.The experimental method uses Nissui Compact Dry to observe the situation in different types of microorganisms. After the drug is dissolved in water, it is implanted in a petri dish, and the presence of different microorganisms is detected through different antibody reactions to confirm whether the drug has some toxicology in the gut.[Results and Discussion]From the above experimental results, it can be known that among the effects of Sacubitril and Valsartan on the basic microbial flora of the human body, low doses had no significant effect on Escherichia coli or intestinal bacteria. If Sacubitril or Valsartan with a high concentration of 3mg/ml is used alone or under the stimulation of a high concentration of the two drugs, it has a significant inhibitory effect on Escherichia coli. However, in terms of the effect on intestinal bacteria, high concentration of Sacubitril has a more significant inhibitory effect on intestinal bacteria, while high concentration of Valsartan has a less significant inhibitory effect on intestinal bacteria. The inhibitory effect of the combination of the two drugs on intestinal bacteria is also less significant.[Conclusion]The results of this study can be used as a further reference for the possible side effects of the clinical use of Sacubitril and Valsartan on the intestinal tract of patients,

Keywords: sacubitril, valsartan, entresto, congestive heart failure (CHF)

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Authors: Mohamed Moustafa Mahmoud Sedky

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The double-fed induction generator wind turbine has recently received a great attention. The steady state performance and response of double fed induction generator (DFIG) based wind turbine are now well understood. This paper presents the analysis of stator and rotor flux linkage dq models operation of DFIG under different faults and at different locations.

Keywords: double fed induction motor, wind energy, flux linkage, short circuit

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Authors: Claudia Matassa, Matthias Hohne, Dominic Ormerod, Yamini Satyawali

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Chiral amines integrate the backbone of several active pharmaceutical ingredients (APIs) used in modern medicine for the treatment of a vast range of diseases. Despite the demand, their synthesis remains challenging. Besides a range of chemicals and enzymatical methods, chiral amine synthesis using transaminases (EC 2.6.1.W) represents a useful alternative to access this important class of compounds. Even though transaminases exhibit excellent stereo and regioselectivity and the potential for high yield, the reaction suffers from a number of challenges, including the thermodynamic equilibrium, product inhibition, and low substrate solubility. In this work, we demonstrate a membrane assisted strategy for addressing these challenges. It involves the use of high molecular weight (HMW) amine donors for the transaminase-catalyzed synthesis of 4-phenyl-2-butylamine in both aqueous and organic solvent media. In contrast to common amine donors such as alanine or isopropylamine, these large molecules, provided in excess for thermodynamic equilibrium shifting, are easily retained by commercial nanofiltration membranes; thus a selective permeation of the desired smaller product amine is possible. The enzymatic transamination in aqueous media, combined with selective product removal shifted the equilibrium enhancing substrate conversion by an additional 25% compared to the control reaction. Along with very efficient amine product removal, there was undesirable loss of ketone substrate and low product concentration was achieved. The system was therefore further improved by performing the reaction in organic solvent (n-heptane). Coupling the reaction system with membrane-assisted product removal resulted in a highly concentrated and relatively pure ( > 97%) product solution. Moreover, a product yield of 60% was reached, compared to 15% without product removal.

Keywords: amine donor, chiral amines, in situ product removal, transamination

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Authors: Pawan Kumar Gupta, Sumana Ghosh

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Parkinson's Disease (PD) is a long-term neurodegenerative movement disorder of the central nervous system with vast symptoms related to the motor system. The common symptoms of PD are tremor, rigidity, bradykinesia/akinesia, and postural instability, but the clinical symptom includes other motor and non‐motor issues. The motor symptoms of the disease are consequence of death of the neurons in a region of the midbrain known as substantia nigra pars compacta, leading to decreased level of a neurotransmitter known as dopamine. The cause of this neuron death is not clearly known but involves formation of Lewy bodies, an abnormal aggregation or clumping of the protein alpha-synuclein in the neurons. Unfortunately, there is no cure for PD, and the management of this disease is challenging. Therefore, it is critical for a patient to be diagnosed at early stages. A limited choice of drugs is available to improve the symptoms, but those become less and less effective over time. Apart from that, with rapid growth in the field of science and technology, other methods such as multi-area brain stimulation are used to treat patients. In order to develop advanced techniques and to support drug development for treating PD patients, an accurate mathematical model is needed to explain the underlying relationship of dopamine secretion in the brain with the hand tremors. There has been a lot of effort in the past few decades on modeling PD tremors and treatment effects from a computational point of view. These models can effectively save time as well as the cost of drug development for the pharmaceutical industry and be helpful for selecting appropriate treatment mechanisms among all possible options. In this review paper, an effort is made to investigate studies on PD modeling and analysis and to highlight some of the key advances in the field over the past centuries with discussion on the current challenges.

Keywords: Parkinson's disease, deep brain stimulation, tremor, modeling

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Authors: Abdel-Monem Sayed Mohamed

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Egypt rapidly growing development is accompanied by increasing levels of standard living particular in its urban areas. However, there is a limited experience in quantifying the sources of risk management in Egypt and in designing efficient strategies to keep away serious impacts of earthquakes. From the historical point of view and recent instrumental records, there are some seismo-active regions in Egypt, where some significant earthquakes had occurred in different places. The special tectonic features in Egypt: Aswan, Greater Cairo, Red Sea and Sinai Peninsula regions are the territories of a high seismic risk, which have to be monitored by up-to date technologies. The investigations of the seismic events and interpretations led to evaluate the seismic hazard for disaster prevention and for the safety of the dense populated regions and the vital national projects as the High Dam. In addition to the monitoring of the recent crustal movements, the most powerful technique of satellite geodesy GPS are used where geodetic networks are covering such seismo-active regions. The results from the data sets are compared and combined in order to determine the main characteristics of the deformation and hazard estimation for specified regions. The final compiled output from the seismological and geodetic analysis threw lights upon the geodynamical regime of these seismo-active regions and put Aswan and Greater Cairo under the lowest class according to horizontal crustal strains classifications. This work will serve a basis for the development of so-called catastrophic models and can be further used for catastrophic risk management. Also, this work is trying to evaluate risk of large catastrophic losses within the important regions including the High Dam, strategic buildings and archeological sites. Studies on possible scenarios of earthquakes and losses are a critical issue for decision making in insurance as a part of mitigation measures.

Keywords: b-value, Gumbel distribution, seismic and GPS data, strain parameters

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Authors: Zinhle Cindi, Collet Dandara, Mpiko Ntsekhe, Edson Makambwa, Miguel Larceda

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Background: Warfarin is the most commonly used drug in the management of thromboembolic disease. However, there is a huge variability in the time, number of doses or starting doses for patients to achieve the required international normalised ratio (INR) which is compounded by a narrow therapeutic index. Many genetic-association studies have reported on European and Asian populations which have led to the designing of specific algorithms that are now being used to assist in warfarin dosing. However, very few or no studies have looked at the pharmacogenetics of warfarin in African populations, yet, huge differences in dosage requirements to reach the same INR have been observed. Objective: We set out to investigate the distribution of 3 SNPs CYP4F2 c.1347C > T, VKORC1 g.-1639G > A and VKORC1 c.1173C > T among South African Mixed Ancestry (MA) and Black African patients. Methods: DNA was extracted from 383 participants and subsequently genotyped using PCR/RFLP for the CYP4F2 c.1347 (V433M) (rs2108622), VKORC1 g.-1639 (rs9923231) and VKORC1 c.1173 (rs9934438) SNPs. Results: Comparing the Black and MA groups, significant differences were observed in the distribution of the following genotypes; CYP4F2 c.1347C/T (23% vs. 39% p=0.03). All VKORC1 g.-1639G > A genotypes (p < 0.006) and all VKORC1 c.1173C > T genotypes (p < 0.007). Conclusion: CYP4F2 c.1347T (V433M) reduces CYP4F2 protein levels and therefore expected to affect the amount of warfarin needed to block vitamin k recycling. The VKORC1 g-1639A variant alters transcriptional regulation therefore affecting the function of vitamin k epoxide reductase in vitamin k production. The VKORC1 c.1173T variant reduces the enzyme activity of VKORC1 consequently enhancing the effectiveness of warfarin. These are preliminary results; more genetic characterization is required to understand all the genetic determinants affecting how patients respond to warfarin.

Keywords: algorithms, pharmacogenetics, thromboembolic disease, warfarin

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Authors: Chukwuka Justus Iwegbu, Monye Christopher Prayer

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Propeller aircraft engines, and more generally engines with a large rotating part (turboprops, high bypass ratio turbojets, etc.) are widely used in the industry and are subject to numerous developments in order to reduce their fuel consumption. In this context, unconventional architectures such as open rotors or distributed propulsion appear, and it is necessary to consider the influence of these systems on the aircraft's stability in flight. Indeed, the tendency to lengthen the blades and wings on which these propulsion devices are fixed increases their flexibility and accentuates the risk of whirl flutter. This phenomenon of aeroelastic instability is due to the precession movement of the axis of rotation of the propeller, which changes the angle of attack of the flow on the blades and creates unsteady aerodynamic forces and moments that can amplify the motion and make it unstable. The whirl flutter instability can ultimately lead to the destruction of the engine. We note the existence of a critical speed of the incident flow. If the flow velocity is lower than this value, the motion is damped and the system is stable, whereas beyond this value, the flow provides energy to the system (negative damping) and the motion becomes unstable. A simple model of whirl flutter is based on the work of Houbolt & Reed who proposed an analytical expression of the aerodynamic load on a rigid blade propeller whose axis orientation suffers small perturbations. Their work considered a propeller subjected to pitch and yaw movements, a flow undisturbed by the blades and a propeller not generating any thrust in the absence of precession. The unsteady aerodynamic forces were then obtained using the thin airfoil theory and the strip theory. In the present study, the unsteady aerodynamic loads are expressed for a general movement of the propeller (not only pitch and yaw). The acceleration and rotation of the flow by the propeller are modeled using a Blade Element Momentum Theory (BEMT) approach, which also enable to take into account the thrust generated by the blades. It appears that the thrust has a stabilizing effect. The aerodynamic model is further developed using Theodorsen theory. A reduced order model of the aerodynamic load is finally constructed in order to perform linear stability analysis.

Keywords: advancing, entrepreneurial, knowledge, industralization

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Authors: Anung Style Bukhori, Ani Dijah Rahajoe

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Poverty poses a significant challenge in Indonesia, requiring an effective analytical approach to understand and address this issue. In this research, we applied the Naïve Bayes classification method to examine and classify poverty data in Indonesia. The main focus is on classifying data using RapidMiner, a powerful data analysis platform. The analysis process involves data splitting to train and test the classification model. First, we collected and prepared a poverty dataset that includes various factors such as education, employment, and health..The experimental results indicate that the Naïve Bayes classification model can provide accurate predictions regarding the risk of poverty. The use of RapidMiner in the analysis process offers flexibility and efficiency in evaluating the model's performance. The classification produces several values to serve as the standard for classifying poverty data in Indonesia using Naive Bayes. The accuracy result obtained is 40.26%, with a moderate recall result of 35.94%, a high recall result of 63.16%, and a low recall result of 38.03%. The precision for the moderate class is 58.97%, for the high class is 17.39%, and for the low class is 58.70%. These results can be seen from the graph below.

Keywords: poverty, classification, naïve bayes, Indonesia

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Authors: M. K. Benhaoua, A. K. Singh, A. E. H. Benyamina

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In this paper, we propose heuristic for dynamic communications mapping that considers the placement of communications in order to optimize the overall performance. The mapping technique uses a newly proposed Algorithm to place communications between the tasks. The placement we propose of the communications leads to a better optimization of several performance metrics (time and energy consumption). Experimental results show that the proposed mapping approach provides significant performance improvements when compared to those using static routing.

Keywords: Multi-Processor Systems-on-Chip (MPSoCs), Network-on-Chip (NoC), heterogeneous architectures, dynamic mapping heuristics

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Authors: Amr A. El Hanafy, Muhammad I. Qureshi, Jamal Sabir, Mohamed Mutawakil, Mohamed M. Ahmed, Hassan El Ashmaoui, Hassan Ramadan, Mohamed Abou-Alsoud, Mahmoud Abdel Sadek

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β-Lactoglobulin (β-LG) is the dominant non-casein whey protein found in bovine milk and of most ruminants. The amino acid sequence of β-LG along with its 3-dimensional structure illustrates linkage with the lipocalin superfamily. Preliminary studies in goats indicated that milk yield can be influenced by polymorphism in genes coding for whey proteins. The aim of this study is to identify and evaluate the incidence of functional polymorphisms in the exonic and intronic portions of β-LG gene in native Saudi goat breeds (Ardi, Habsi, and Harri). Blood samples were collected from 300 animals (100 for each breed) and genomic DNA was extracted using QIAamp DNA extraction Kit. A fragment of the β-LG gene from exon 7 to 3’ flanking region was amplified with pairs of specific primers. Subsequent digestion with Sac II restriction endonuclease revealed two alleles (A and B) and three different banding patterns or genotypes i.e. AA, AB and BB. The statistical analysis showed that β-LG AA genotype had higher milk yield than β-LG AB and β-LG BB genotypes. Nucleotide sequencing of the selected β-LG fragments was done and submitted to GenBank NCBI (Accession No. KJ544248, KJ588275, KJ588276, KJ783455, KJ783456 and KJ874959). Two already established SNPs in exon 7 (+4601 and +4603) and one fresh SNP in the 3’ UTR region were detected in the β-LG fragments with designated AA genotype. The polymorphisms in exon 7 did not produce any amino acid change. Phylogenetic analysis on the basis of nucleotide sequences of native Saudi goats indicated evolutional similarity with the GenBank reference sequences of goat, Bubalus bubalis and Bos taurus.

Keywords: β-Lactoglobulin, Saudi goats, PCR-RFLP, functional polymorphism, nucleotide sequencing, phylogenetic analysis

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Authors: Sabina-Adriana Floria, Marius Gavrilescu, Florin Leon, Silvia Curteanu, Costel Anton

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Neuroevolution is a subfield of artificial intelligence used to solve various problems in different application areas. Specifically, neuroevolution is a technique that applies biologically inspired methods to generate neural network architectures and optimize their parameters automatically. In this paper, we use different biologically inspired optimization algorithms in an ensemble strategy with the aim of training multilayer perceptron neural networks, resulting in regression models used to simulate the industrial chemical process of obtaining bricks from silicone-based materials. Installations in the raw ceramics industry, i.e., bricks, are characterized by significant energy consumption and large quantities of emissions. In addition, the initial conditions that were taken into account during the design and commissioning of the installation can change over time, which leads to the need to add new mixes to adjust the operating conditions for the desired purpose, e.g., material properties and energy saving. The present approach follows the study by simulation of a process of obtaining bricks from silicone-based materials, i.e., the modeling and optimization of the process. Optimization aims to determine the working conditions that minimize the emissions represented by nitrogen monoxide. We first use a search procedure to find the best values for the parameters of various biologically inspired optimization algorithms. Then, we propose an adaptive ensemble strategy that uses only a subset of the best algorithms identified in the search stage. The adaptive ensemble strategy combines the results of selected algorithms and automatically assigns more processing capacity to the more efficient algorithms. Their efficiency may also vary at different stages of the optimization process. In a given ensemble iteration, the most efficient algorithms aim to maintain good convergence, while the less efficient algorithms can improve population diversity. The proposed adaptive ensemble strategy outperforms the individual optimizers and the non-adaptive ensemble strategy in convergence speed, and the obtained results provide lower error values.

Keywords: optimization, biologically inspired algorithm, neuroevolution, ensembles, bricks, emission minimization

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Authors: Ziyad S. Haidar

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Background: Saliva plays a major role in maintaining oral and dental health (consequently, general health and well-being). Where it normally bathes the oral cavity and acts as a clearing agent. This becomes more apparent when the amount and quality of salivare significantly reduced due to medications, salivary gland neoplasms, disorders such as Sjögren’s syndrome, and especially ionizing radiation therapy for tumors of the head and neck, the fifth most common malignancy worldwide, during which the salivary glands are included within the radiation field or zone. Clinically, patients affected by salivary gland dysfunction often opt to terminate their radiotherapy course prematurely because they become malnourished and experience a significant decrease in their quality of life. Accordingly, the development of an alternative treatment to restore or regenerate damaged salivary gland tissue is eagerly awaited. Likewise, the formulation of a radioprotection modality and early damage prevention strategy is also highly desirable. Objectives: To assess the pre-clinical radio-protective effect as well as the reparative/regenerative potential of layer-by-layer self-assembled lipid-polymer-based core-shell nanocapsules designed and fine-tuned in this experimental work for the sequential (ordered) release of dual cytokines, following a single local administration (direct injection) into a murine sub-mandibular salivary gland model of irradiation. Methods: The formulated core-shell nanocapsules were characterized by physical-chemical-mechanically pre-/post-loading with the drugs (in solution and powder formats), followed by optimizing the pharmaco-kinetic profile. Then, nanosuspensions were administered directly into the salivary glands, 24hrs pre-irradiation (PBS, un-loaded nanocapsules, and individual and combined vehicle-free cytokines were injected into the control glands for an in-depth comparative analysis). External irradiation at an elevated dose of 18Gy (revised from our previous 15Gy model) was exposed to the head-and-neck region of C57BL/6 mice. Salivary flow rate (un-stimulated) and salivary protein content/excretion were regularly assessed using an enzyme-linked immunosorbent assay (3-month period). Histological and histomorphometric evaluation and apoptosis/proliferation analysis followed by local versus systemic bio-distribution and immuno-histochemical assays were then performed on all harvested major organs (at the distinct experimental end-points). Results: Monodisperse, stable, and cytocompatible nanocapsules capable of maintaining the bioactivity of the encapsulant within the different compartments with the core and shell and with controlled/customizable pharmaco-kinetics, resulted, as is illustrated in the graphical abstract (Figure) below. The experimental animals demonstrated a significant increase in salivary flow rates when compared to the controls. Herein, salivary protein content was comparable to the pre-irradiation (baseline) level. Histomorphometry further confirmed the biocompatibility and localization of the nanocapsules, in vivo, into the site of injection. Acinar cells showed fewer vacuoles and nuclear aberration in the experimental group, while the amount of mucin was higher in controls. Overall, fewer apoptotic activities were detected by a Terminal deoxynucleotidyl Transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay and proliferative rates were similar to the controls, suggesting an interesting reparative and regenerative potential of irradiation-damaged/-dysfunctional salivary glands. The Figure below exemplifies some of these findings. Conclusions: Biocompatible, reproducible, and customizable self-assembling layer-by-layer core-shell delivery system is formulated and presented. Our findings suggest that localized sequential bioactive delivery of dual cytokines (in specific dose and order) can prevent irradiation-induced damage via reducing apoptosis and also has the potential to promote in situ proliferation of salivary gland cells; maxSALIVA is scalable (Good Manufacturing Practice or GMP production for human clinical trials) and patent-pending.

Keywords: saliva, head and neck cancer, nanotechnology, controlled drug delivery, xerostomia, mucositis, biopolymers, innovation

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Authors: Houda Mnif Sellami, Toshi Umehara, Yuriko Yamazaki, Reie Matoba, Anna Sakashita, Yoshimi Abe, Hiroyuki Otake, Satoko Morita, Yoshitaka Akiyama, Chieko Morisawa, Eiji Omura, Masako Yazawa, Yoshie Koike, Mitsugu Tokunaga, Seiki Wada, Shinya Minagawa, Masafumi Matsuda

Abstract:

Childhood obesity has been, for decades, a very serious public health problem worldwide. Some Asian countries have already reached alarming rates, as lifestyle changed dramatically in this part of the world. In many concerned countries, strategies including educational, promotional and awareness-raising activities have been established to combat obesity within kids. Objective: To estimate the obesity and also the underweight trends of Japanese kids from 5 to 17 years, by single year of age and by gender, over the last decade. Methods We used the data from the cross-sectional annual Nationwide surveys (National Nutrition Survey, Japan, Ministry of education, culture, sports, science and technology) conducted from 2007 to 2016. We compared trajectories of obesity prevalence, with the data on sex and age groups. We also analyzed energy and macronutrients intakes of Japanese kids using Ministry of Health, Labor and Welfare-Japan annual data, from 2007 to 2014. Results: From 2007 to 2016, Boys obesity was higher than Girls obesity for the over 6 YO participants. Both Boys and Girls obesity trends had 2 peaks of prevalence at (11-13 YO) and then at (15-16 YO). From 2007 to 2012, Kids obesity decreased considerably in both sex and all year of age; then obesity decline was more modest till 2016.On the other side, Kids underweight prevalence increased in both sexes. The macronutrients analyze couldn’t show an evident association between obesity trends and foods intake. Conclusion: Japanese kids’ obesity has been decreased since 2007, in opposition to some other countries reports. We didn’t find an observed association with food intake using Health Ministry data; we need further investigation to estimate energy intake, lifestyle and physical activity by year of age to know whether there is any possible relation.

Keywords: childhood, Japan, obesity, underweight

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Authors: WonSun Chen, James Boylan, Erwin Muharemovic, Denny Meyer

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In Australia, drivers aged between 18 and 24 remained at high risk of road fatality over the last decade. Despite the successful implementation of the Graduated Licensing System (GLS) that supports young drivers in their early phases of driving, the road fatality statistics for these drivers remains high. In response to these statistics, studies conducted in Australia prior to the start of the COVID-19 pandemic have demonstrated the benefits of using telematics devices for improving driving behaviour, However, the impact of COVID-19 lockdown on young drivers’ driving behaviour has emerged as a global concern. Therefore, this naturalistic study aimed to evaluate and compare the driving behaviour(such as acceleration, braking, speeding, etc.) of young drivers with the adoption of in-vehicle telematics devices. Forty-two drivers aged between 18 and 30 and residing in the Australian state of Victoria participated in this study during the period of May to October 2022. All participants drove with the telematics devices during the first 30-day. At the start of the second 30-day, twenty-one participants were randomised to an intervention group where they were provided with an additional telematics ray device that provided visual feedback to the drivers, especially when they committed to aggressive driving behaviour. The remaining twenty-one participants remined their driving journeys without the extra telematics ray device (control group). Such trustworthy data enabled the assessment of changes in the driving behaviour of these young drivers using a machine learning approach in Python. Results are expected to show participants from the intervention group will show improvements in their driving behaviour compared to those from the control group.Furthermore, the telematics data enable the assessment and quantification of such improvements in driving behaviour. The findings from this study are anticipated to shed some light in guiding the development of customised campaigns and interventions to further address the high road fatality among young drivers in Australia.

Keywords: driving behaviour, naturalistic study, telematics data, young drivers

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Authors: Ruolan Zhang, Ryo Imai, Naoko Senda, Tomoyuki Sakai

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Enzymes have attracted increasing attentions in industrial manufacturing for their applicability in catalyzing complex chemical reactions under mild conditions. Directed evolution has become a powerful approach to optimize enzymes and exploit their full potentials under the circumstance of insufficient structure-function knowledge. With the incorporation of cell-free synthetic biotechnology, rapid enzyme synthesis can be realized because no cloning procedure such as transfection is needed. Its open environment also enables direct enzyme measurement. These properties of cell-free biotechnology lead to excellent throughput of enzymes generation. However, the capabilities of current screening methods have limitations. Fluorescence-based assay needs applicable fluorescent label, and the reliability of acquired enzymatic activity is influenced by fluorescent label’s binding affinity and photostability. To acquire the natural activity of an enzyme, another method is to combine pre-screening step and high-performance liquid chromatography (HPLC) measurement. But its throughput is limited by necessary time investment. Hundreds of variants are selected from libraries, and their enzymatic activities are then identified one by one by HPLC. The turn-around-time is 30 minutes for one sample by HPLC, which limits the acquirable enzyme improvement within reasonable time. To achieve the real high-throughput enzyme screening, i.e., obtain reliable enzyme improvement within reasonable time, a widely applicable high-throughput measurement of enzymatic reactions is highly demanded. Here, a high-throughput screening method using broadband coherent anti-Stokes Raman spectroscopy (CARS) was proposed. CARS is one of coherent Raman spectroscopy, which can identify label-free chemical components specifically from their inherent molecular vibration. These characteristic vibrational signals are generated from different vibrational modes of chemical bonds. With the broadband CARS, chemicals in one sample can be identified from their signals in one broadband CARS spectrum. Moreover, it can magnify the signal levels to several orders of magnitude greater than spontaneous Raman systems, and therefore has the potential to evaluate chemical's concentration rapidly. As a demonstration of screening with CARS, alcohol dehydrogenase, which converts ethanol and nicotinamide adenine dinucleotide oxidized form (NAD+) to acetaldehyde and nicotinamide adenine dinucleotide reduced form (NADH), was used. The signal of NADH at 1660 cm⁻¹, which is generated from nicotinamide in NADH, was utilized to measure the concentration of it. The evaluation time for CARS signal of NADH was determined to be as short as 0.33 seconds while having a system sensitivity of 2.5 mM. The time course of alcohol dehydrogenase reaction was successfully measured from increasing signal intensity of NADH. This measurement result of CARS was consistent with the result of a conventional method, UV-Vis. CARS is expected to have application in high-throughput enzyme screening and realize more reliable enzyme improvement within reasonable time.

Keywords: Coherent Anti-Stokes Raman Spectroscopy, CARS, directed evolution, enzyme screening, Raman spectroscopy

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