Search results for: receptor activator of nuclear factor kappa-B ligand

Authors: Huafeng Wei

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Failures of developing new drugs primarily based on the amyloid pathology hypothesis after decades of efforts internationally lead to changes of focus targeting alternative pathways of pathology in Alzheimer’s disease (AD). Disruption of intracellular Ca2+ homeostasis, especially the pathological and excessive Ca2+ release from the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) Ca2+ channels, has been considered an upstream pathology resulting in major AD pathologies, such as amyloid and Tau pathology, mitochondria damage and inflammation, etc. Therefore, dantrolene, an inhibitor of RyRs that reduces the pathological Ca2+ release from ER and a clinically available drug for the treatment of malignant hyperthermia and muscle spasm, is expected to ameliorate AD multiple pathologies synapse and cognitive dysfunction. Our own studies indicated that dantrolene ameliorated impairment of neurogenesis and synaptogenesis in neurons developed from induced pluripotent stem cells (iPSCs) originated from skin fibroblasts of either familiar (FAD) or sporadic (SAD) AD by restoring intracellular Ca2+ homeostasis. Intranasal administration of dantrolene significantly increased its passage across the blood-brain barrier (BBB) and, therefore its brain concentrations and durations. This can render dantrolene a more effective therapeutic drug with fewer side effects for chronic AD treatment. This review summarizes the potential therapeutic and side effects of dantrolene and repurposes intranasal dantrolene as a disease-modifying drug for future AD treatment.

Keywords: Alzheimer's disease, calcium, drug development, dementia, neurodegeneration, neurogenesis

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Authors: Francesca La Rosa , Marina Saresella, Mario Clerici, Michael Heneka

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Neuroinflammation plays a key role in the modulation of the pathogenesis of neurodegenerative disorder such as Alzheimer's Disease (AD). Microglia, the main immune effector of the brain, are able to migrate to sites of Amyloid-beta (Aβ) deposition to eliminate Aβ phagocytosis upon activation by multiple receptors: Toll like receptors and scavenger receptors. The issue of whether microglia are able to eliminate pathological lesions such as neurofibrillary tangles or senile plaques from AD brain still remains the matter of controversy. Recent data suggest that the Nod Like Receptor 3 (NLRP3), multiprotein inflammasome complexes, plays a role in AD, as its activation in the microglia by Aβ triggers. IL-1β is produced as a biologically inactive pro-form and requires caspase-1 for activation and secretion. Caspase-1 activity is controlled by inflammasomes. We investigate about the importance of inflammasomes complex in the Aβ phagocytosis and its degradation. The preliminary results of phagocytosis assay and immunofluorescent experiment on primary Microglia cells to lipopolysaccharide (LPS) an Aβ exposure show that a previous treatment with LPS reduce Aβ phagocytosis. Different results were obtained in Primary Microglia wild type, NLRP3 and ASC Knockout suggesting a real inflammasomes involvement in Alzheimer's pathology. Inflammasomes inactivation reduces the production of inflammatory cytokines prolonging the protective activity of microglia and Aβ clearance, featuring a typical microglia phenotype of the early stage of AD disease.

Keywords: Alzheimer disease, innate immunity, neuroinflammation, NLRP3

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Authors: Jing Yu Pan, Dahai Liu

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Airlines in the US have taken protective measures to battle the COVID-19 pandemic, with a mask mandate being the most important one, especially in the aircraft cabin. As the industry is recovering from the pandemic, mask-wearing will eventually become a personal choice during flight. Nevertheless, COVID-19 will continue to create uncertainty for a long time into the future, making it necessary to understand the attitude and voluntary use of masks by air travelers on airplanes even after masks are no longer mandatory. This study aimed to understand the relationship between demographic characteristics and mask-wearing intention in the US. For age, gender, income, educational, and ethnicity groups, this study examined three factors – subjective norms, risk avoidance, and information seeking and their influence on the mask-wearing intention onboard airplanes during COVID-19 and whether or not attitude toward masks was an important mediator. The results show that all demographic factors except gender could help to explain the group variations in factor impact and the mediating effect in mask-wearing intentions. In particular, Asian travelers had mask-wearing intentions that were not affected by attitude either directly or indirectly. These findings provide useful implications to enhance the health and safety of air travelers, especially in the US, where opposing views toward mask-wearing still widely exist.

Keywords: COVID-19, passenger demographics, aircraft cabin, mask-wearing intention, attitude as mediator

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Authors: Masaki Yamaguchi, Daimei Sasayama, Shinsuke Washizuka

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The goal of this study was to examine the possibility of salivary cytokines for the screening of attention deficit hyperactivity disorder (ADHD) in children. We carried out a case-control study, including 19 children with ADHD and 17 healthy children (controls). A multiplex bead array immunoassay was used to conduct a multi-analysis of 27 different salivary cytokines. Six salivary cytokines (interleukin (IL)-1β, IL-8, IL12p70, granulocyte colony-stimulating factor (G-CSF), interferon gamma (IFN-γ), and vascular endothelial growth factor (VEGF)) were significantly associated with the presence of ADHD (p < 0.05). An informative salivary cytokine panel was developed using VEGF by logistic regression analysis (odds ratio: 0.251). Receiver operating characteristic analysis revealed that assessment of a panel using VEGF showed “good” capability for discriminating between ADHD patients and controls (area under the curve: 0.778). ADHD has been hypothesized to be associated with reduced cerebral blood flow in the frontal cortex, due to reduced VEGF levels. Our study highlights the possibility of utilizing differential salivary cytokine levels for point-of-care testing (POCT) of biomarkers in children with ADHD.

Keywords: cytokine, saliva, attention deficit hyperactivity disorder, child

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Authors: M.J. Seddighi, Moradchelleh, M. Keyvan

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The ultimate goal in building a city is to provide pleasant, comfortable and nurturing environment as a context of public life. City environment establishes strong connection with people and their surrounding habitant, acting as relevance in social interactions between citizens itself. Urban environment and appropriate municipal facilities are the only way for proper communication between city and citizens and also citizens themselves.There is a need for complement elements between buildings and constructions to settling city life through which the move, comfort, reactions and anxiety will adjust and reflect the spirit to the city. In the surging development of society, urban’ spaces are encountered evolution, sometimes causing the symbols to fade and waste, and as a result, leading to destroy belongs among humans and their physical liquidate. Houses and living spaces exhibit materialistic reflection of life style. In the other words, way of life makes the symbolic essence of living spaces. In addition, it is of sociocultural factor of lifestyle, consisting the concepts and culture, morality, worldview, and national character. Culture is responsible for some crucial meaningful needs which can be wide because they depend on various causes such as perception and interpretation of believes, philosophy of life, interaction with neighbors and protection against climate and enemies. The bi-lateral relationship between human and nature is the main factor that needs to be properly addressed. It is because of the fact that the approach which is taken against landscape and nature has a pertinent influence on creation and shaping the structure of a house. The first response of human in tackling the environment is to build a “shelter” and place as dwelling. This has been a crucial factor in all time periods. In the proposed study, dwelling in Khorasgan’ Stream, as an area located in one of the important historical city of Iran, has been studied. Khorasgan’ Stream is the basic constituent elements of the present architectural form of Isfahan. The influence of Islamic spiritual culture and neighborhood with the historical elements on the dwelling of the selected location, subsequently on other regions of the town are presented.

Keywords: dwelling, neighborhood, historical, Islamic, architectural elements

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Authors: Jameson McFarlane, Thorne J. McFarlane, Leon Bernard

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Social network sites (SNS) is an emerging phenomenon that is here to stay. The popularity and the ubiquity of the SNS technology are undeniable. Because most SNS are free and easy to use people from all walks of life and from almost any age are attracted to that technology. College age students are by far the largest segment of the population using SNS. Since most SNS have been adapted for mobile devices, not only do you find students using this technology in their study, while working on labs or on projects, a substantial number of students have been found to use SNS even while listening to lectures. This study found that SNS use has a significant negative impact on the grade point average of college students particularly in the first semester. However, this negative impact is greatly diminished by the end of the third semester partly because the students have adjusted satisfactorily to the challenges of college or because they have learned how to adequately manage their time. It was established that the kinds of activities the students are engaged in during the SNS use are the leading factor affecting academic performance. Of those activities, using SNS during a lecture or while studying is the foremost contributing factor to lower academic performance. This is due to “cognitive” or “information” bottleneck, a condition in which the students find it very difficult to multitask or to switch between resources leading to inefficiency in information retention and thus, educational performance.

Keywords: social network sites, social network analysis, regression coefficient, psychological engagement

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Authors: Rami S. Alasmari, Abdullah Al Zahrani, Hattan A. Hassani, Hattan A. Hassani, Nawwaf A. Almalky, Abdullah F. Bokhari, Alwalied A. Hafez

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Diabetes mellitus type 2 (DMT2) is a major chronic condition that is considered common among elderly people, with multiple potential complications that could contribute to falls. However, this concept is not well understood, thus, the aim of this study is to determine whether diabetes is an independent risk factor for falls in elderly. In this observational cross-sectional study, 309 diabetic patients aged 60 or more who visited the primary healthcare centers of the Ministry of National Guard Health Affairs in Jeddah were chosen via convenience sampling method. To collect the data, Semi-structured Fall Risk Assessment questionnaire and Fall Efficacy Score scale were used. The mean age of the participants was estimated to be 68.5 (SD:7.4) years. Among the participants, 48.2% experienced falling before, and 63.1% of them suffered falls in the past 12-months. The results showed that gait problems were independently associated with a higher likelihood of fall among the elderly patients (OR = 1.98, 95%CI, 1.08 to 3.62, p = 0.026. This paper suggests that diabetes mellitus is an independent fall risk factor among elderly. Therefore, identifying such patients as being at higher risk and prompt referral to a specialist falls clinic is recommended.

Keywords: diabetes, fall, elderly, risk factors

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Authors: Tery Nehemia Nugraha Joseph, J. D. P. Wisnubroto

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Thyroid cancer is a healthcare problem with high morbidity and mortality. Follicular adenoma and follicular carcinoma are thyroid tumors from the thyroid follicular cells differentiation with a microfollicular pattern that consists of follicular cuboidal cells. vascular endothelial growth factor (VEGF) is a potent and powerful mitogen for endothelial cells and increases vascular permeability. Therefore, due to an increase in thyroid-stimulating hormone (TSH), VEGF production is activated in the thyroid that leads to the end of mitogenic TSH stimulation and initiation of angiogenesis. The differences in VEGF levels in the follicular carcinoma of thyroid tissue with follicular adenoma thyroid can be used as a basis in differentiating the two types of neoplasms. This study aims to analyze VEGF in the serum so that it can be used to differentiate the types of thyroid carcinoma before surgery. This study uses a cross-sectional research design. Samples were carried out by taking serum samples, and the VEGF levels were calculated. Data were analyzed using the Mann-Whitney test. The results found a significant difference between VEGF levels in the follicular carcinoma thyroid group and VEGF levels in the follicular adenoma thyroid group with a value of p = 0.007 (p < 0.05). The results obtained are 560,427 ± 160,506 ng/mL in the type of follicular carcinoma thyroid and 320.943 ± 134.573 ng/mL in the type of follicular adenoma thyroid. VEGF levels between follicular adenoma and follicular carcinoma are different. VEGF levels are higher in follicular carcinoma thyroid than follicular adenoma thyroid.

Keywords: follicular adenoma thyroid, follicular carcinoma thyroid, thyroid, VEGF

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Authors: Hatem A. El-Mezayen, Hossam Darwesh

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Background/Aim: Hepatocellular carcinoma (HCC) is often diagnosed at advanced stage where effective therapies are lacking. Identification of new scoring system is needed to discriminate HCC patients from those with chronic liver disease. Based on the link between vascular endothelial growth factor (VEGF) and HCC progression, we aimed to develop a novel score based on combination of VEGF and routine laboratory tests for early prediction of HCC. Methods: VEGF was assayed for HCC group (123), liver cirrhosis group (210) and control group (50) by Enzyme Linked Immunosorbent Assay (ELISA). Data from all groups were retrospectively analyzed including α feto protein (AFP), international normalized ratio (INR), albumin and platelet count, transaminases, and age. Areas under ROC curve were used to develop the score. Results: A novel index named hepatocellular carcinoma-vascular endothelial growth factor score (HCC-VEGF score)=1.26 (numerical constant) + 0.05 ×AFP (U L-1)+0.038 × VEGF(ng ml-1)+0.004× INR –1.02 × Albumin (g l-1)–0.002 × Platelet count × 109 l-1 was developed. HCC-VEGF score produce area under ROC curve of 0.98 for discriminating HCC patients from liver cirrhosis with sensitivity of 91% and specificity of 82% at cut-off 4.4 (ie less than 4.4 considered cirrhosis and greater than 4.4 considered HCC). Conclusion: Hepatocellular carcinoma-VEGF score could replace AFP in HCC screening and follow up of cirrhotic patients.

Keywords: Hepatocellular carcinoma, cirrhosis, HCV, diagnosis, tumor markers

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Authors: Aram Yakoby, Yossef H. Hatzor, Shmulik Pinkert

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This work presents an applied engineering method for evaluating the stability of underground openings under conditions of uncertainty. The developed method is demonstrated by a comprehensive parametric study on a case of large-diameter vertical borehole stability analysis, with uncertainties regarding the in-situ stress distribution. To this aim, a safety factor analysis is performed for the stability of both supported and unsupported boreholes. In the analysis, we used analytic geomechanical calculations and advanced numerical modeling to evaluate the estimated stress field. In addition, the work presents the development of a boundary condition for the numerical model that fits the nature of the problem and yields excellent accuracy. The borehole stability analysis is studied in terms of (1) the stress ratio in the vertical and horizontal directions, (2) the mechanical properties and geometry of the support system, and (3) the parametric sensitivity. The method's results are studied in light of a real case study of an underground waste disposal site. The conclusions of this study focus on the developed method for capturing the parametric uncertainty, the definition of critical geological depths, the criteria for implementing structural support, and the effectiveness of further in-situ investigations.

Keywords: borehole stability, in-situ stress, parametric study, factor of safety

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Authors: Temur Chilachava

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In work the new nonlinear mathematical model describing assimilation of the people (population) with some less widespread language by two states with two various widespread languages, taking into account demographic factor is offered. In model three subjects are considered: the population and government institutions with the widespread first language, influencing by means of state and administrative resources on the third population with some less widespread language for the purpose of their assimilation; the population and government institutions with the widespread second language, influencing by means of state and administrative resources on the third population with some less widespread language for the purpose of their assimilation; the third population (probably small state formation, an autonomy), exposed to bilateral assimilation from two rather powerful states. Earlier by us it was shown that in case of zero demographic factor of all three subjects, the population with less widespread language completely assimilates the states with two various widespread languages, and the result of assimilation (redistribution of the assimilated population) is connected with initial quantities, technological and economic capabilities of the assimilating states. In considered model taking into account demographic factor natural decrease in the population of the assimilating states and a natural increase of the population which has undergone bilateral assimilation is supposed. At some ratios between coefficients of natural change of the population of the assimilating states, and also assimilation coefficients, for nonlinear system of three differential equations are received the two first integral. Cases of two powerful states assimilating the population of small state formation (autonomy), with different number of the population, both with identical and with various economic and technological capabilities are considered. It is shown that in the first case the problem is actually reduced to nonlinear system of two differential equations describing the classical model "predator - the victim", thus, naturally a role of the victim plays the population which has undergone assimilation, and a predator role the population of one of the assimilating states. The population of the second assimilating state in the first case changes in proportion (the coefficient of proportionality is equal to the relation of the population of assimilators in an initial time point) to the population of the first assimilator. In the second case the problem is actually reduced to nonlinear system of two differential equations describing type model "a predator – the victim", with the closed integrated curves on the phase plane. In both cases there is no full assimilation of the population to less widespread language. Intervals of change of number of the population of all three objects of model are found. The considered mathematical models which in some approach can model real situations, with the real assimilating countries and the state formations (an autonomy or formation with the unrecognized status), undergone to bilateral assimilation, show that for them the only possibility to avoid from assimilation is the natural demographic increase in population and hope for natural decrease in the population of the assimilating states.

Keywords: nonlinear mathematical model, bilateral assimilation, demographic factor, first integrals, result of assimilation, intervals of change of number of the population

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Authors: Ahmed Sami Hammami, Mohamed Jellazi

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Background: The aim of the study is to evaluate the magnitude of different psychological outcomes among Tunisian health care professionals (HCP) during the COVID-19 pandemic and to identify the associated factors. Methods: HCP completed a cross-sectional questionnaire from April 4th to April, 28th 2020. The survey collected demographic information, factors that may interfere with the psychological outcomes, behavior changes and mental health measurements. The latter was assessed through 3 scales; the 7-item questions Insomnia Severity Index, the 2-item Patient Health Questionnaire and the 2-item Generalized Anxiety Disorder. Multivariable logistic regression was conducted to identify factors associated with psychological outcomes. Results: A total of 503 HCP successfully completed the survey; among those, n=493 consented to enroll in the study, 411 [83.4%] were physicians, 323 [64.2%] were women and 271 [55%] had a second-line working position. A significant proportion of HCP had anxiety 35.7%, depression 35.1% and insomnia 23.7%. Females, those with psychiatric history and those using public transport exhibited the highest proportions for overall symptoms compared to other groups e.g., depression among females vs. males: 44,9% vs. 18,2%, P=0.00. Those with a previous medical history and nurses, had more anxiety and insomnia compared to other groups e.g. anxiety among nurses vs. interns/residents vs. attending 45,1% vs 36,1% vs 27,5%; p=0.04. Multivariable logistic regression showed that female gender was a risk factor for all psychological outcomes e.g. female sex increased the odds of anxiety by 2.86; 95% confidence interval [CI], 1, 78-4, 60; P=0.00, whereas having a psychiatric history was a risk factor for both anxiety and insomnia. (e.g. for insomnia OR=2,86; 95% [CI], 1,78-4,60; P=0.00), Having protective equipment was associated with lower risk for depression (OR=0,41; 95% CI, 0,27-0,62; P=0.00) and anxiety. Physical activity was also protective against depression and anxiety (OR=0,41, 95% CI, 0,25-0,67, P=0.00). Conclusion: Psychological symptoms are usually undervalued among HCP, though the COVID-19 pandemic played a major role in exacerbating this burden. Prompt psychological support should be endorsed and simple measures such as physical activity and ensuring the necessary protection are paramount to improve mental health outcomes and the quality of care provided to patients.

Keywords: COVID-19 pandemic, health care professionals, mental health, protective factors, psychological symptoms, risk factors

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Authors: Mariane G. Tadros, Shahira M. Ezzat, Maha M. Salama, Mohamed A. Farag

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In this study, the in vitro anticholinesterase activity of the volatile oils of both O. basilicum and O. africanum was investigated and both samples showed significant activity. As a result, the major constituents of the two oils were isolated using several column chromatography. Linalool, 1,8-cineol and eugenol were isolated from the volatile oil of O. basilicum and camphor was isolated from the volatile oil of O. africanum. The anticholinesterase activity of the isolated compounds were also evaluated where 1,8-cineol showed the highest inhibitory activity followed by camphor. To confirm these activities, learning and memory enhancing effects were tested in mice. Memory impairment was induced by scopolamine, a cholinergic muscarinic receptor antagonist. Anti-amnesic effects of both volatile oils and their terpenoids were investigated by the passive avoidance task in mice. We also examined their effects on brain acetylcholinesterase activity. Results showed that scopolamine-induced cognitive dysfunction was significantly attenuated by administration of the volatile oils and their terpenoids, eugenol and camphor, in the passive avoidance task and inhibited brain acetylcholinesterase activity. These results suggest that O. basilicum and O. africanum volatile oils can be good candidates for further studies on Alzheimer’s disease via their acetylcholinesterase inhibitory actions.

Keywords: Ocimum baselicum, Ocimum africanum, GC/MS analysis, anticholinesterase

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Authors: Omar Amoudi, Latifa Al Brashdi

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Construction projects are always subject to risks and uncertainties due to its unique and dynamic nature, outdoor work environment, the wide range of skills employed, various parties involved in addition to situation of construction business environment at large. Altogether, these risks and uncertainties affect projects objectives and lead to cost overruns, delay, and poor quality. Construction projects in Oman often experience cost overruns and delay. Managing these risks and reducing their impacts on construction cost requires firstly identifying these risks, and then analyzing their severity on project cost to obtain deep understanding about these risks. This in turn will assist construction managers in managing and tacking these risks. This paper aims to investigate the main risk factors that affect construction projects cost in the Sultanate of Oman. In order to achieve the main aim, literature review was carried out to identify the main risk factors affecting construction cost. Thirty-three risk factors were identified from the literature. Then, a questionnaire survey was designed and distributed among construction professionals (i.e., client, contractor and consultant) to obtain their opinion toward the probability of occurrence for each risk factor and its possible impact on construction project cost. The collected data was analyzed based on qualitative aspects and in several ways. The severity of each risk factor was obtained by multiplying the probability occurrence of a risk factor with its impact. The findings of this study reveal that the most significant risk factors that have high severity impact on construction project cost are: Change of Oil Price, Delay of Materials and Equipment Delivery, Changes in Laws and Regulations, Improper Budgeting, and Contingencies, Lack of Skilled Workforce and Personnel, Delays Caused by Contractor, Delays of Owner Payments, Delays Caused by Client, and Funding Risk. The results can be used as a basis for construction managers to make informed decisions and produce risk response procedures and strategies to tackle these risks and reduce their negative impacts on construction project cost.

Keywords: construction cost, construction projects, Oman, risk factors, risk management

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Authors: Anushka Naidoo, Veron Ramsuran, Maxwell Chirehwa, Paolo Denti, Kogieleum Naidoo, Helen McIlleron, Nonhlanhla Yende-Zuma, Ravesh Singh, Sinaye Ngcapu, Nesri Padayatachi

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Background: Despite efforts to introduce new drugs and shorter drug regimens for drug-susceptible tuberculosis (TB), the standard first-line treatment has not changed in over 50 years. Rifampicin, isoniazid, and pyrazinamide are critical components of the current standard treatment regimens. Some studies suggest that microbiologic failure and acquired drug resistance are primarily driven by low drug concentrations that result from pharmacokinetic (PK) variability independent of adherence to treatment. Wide between-patient pharmacokinetic variability for rifampin, isoniazid, and pyrazinamide has been reported in prior studies. There may be several reasons for this variability. However, genetic variability in genes coding for drug metabolizing and transporter enzymes have been shown to be a contributing factor for variable tuberculosis drug exposures. Objective: We describe the pharmacokinetics of first-line TB drugs rifampicin, isoniazid, and pyrazinamide and assess the effect of genetic variability in relevant selected drug metabolizing and transporter enzymes on pharmacokinetic parameters of isoniazid and rifampicin. Methods: We conducted the randomized-controlled Improving retreatment success TB trial in Durban, South Africa. The drug regimen included rifampicin, isoniazid, and pyrazinamide. Drug concentrations were measured in plasma, and concentration-time data were analysed using nonlinear-mixed-effects models to quantify the effects of relevant covariates and single nucleotide polymorphisms (SNP’s) of drug metabolizing and transporter genes on rifampicin, isoniazid and pyrazinamide exposure. A total of 25 SNP’s: four NAT2 (used to determine acetylator status), four SLCO1B1, three Pregnane X receptor (NR1), six ABCB1 and eight UGT1A, were selected for analysis in this study. Genotypes were determined for each of the SNP’s using a TaqMan® Genotyping OpenArray™. Results: Among fifty-eight patients studied; 41 (70.7%) were male, 97% black African, 42 (72.4%) HIV co-infected and 40 (95%) on efavirenz-based ART. Median weight, fat-free mass (FFM), and age at baseline were 56.9 kg (interquartile range, IQR: 51.1-65.2), 46.8 kg (IQR: 42.5-50.3) and 37 years (IQR: 31-42), respectively. The pharmacokinetics of rifampicin and pyrazinamide was best described using one-compartment models with first-order absorption and elimination, while for isoniazid two-compartment disposition was used. The median (interquartile range: IQR) AUC (h·mg/L) and Cmax (mg/L) for rifampicin, isoniazid, and pyrazinamide were; 25.62 (23.01-28.53) and 4.85 (4.36-5.40), 10.62 (9.20-12.25) and 2.79 (2.61-2.97), 345.74 (312.03-383.10) and 28.06 (25.01-31.52), respectively. Eighteen percent of patients were classified as rapid acetylators, and 34% and 43% as slow and intermediate acetylators, respectively. Rapid and intermediate acetylator status based on NAT 2 genotype resulted in 2.3 and 1.6 times higher isoniazid clearance than slow acetylators. We found no effects of the SLCO1B1 genotypes on rifampicin pharmacokinetics. Conclusion: Plasma concentrations of rifampicin, isoniazid, and pyrazinamide were low overall in our patients. Isoniazid clearance was high overall and as expected higher in rapid and intermediate acetylators resulting in lower drug exposures. In contrast to reports from previous South African or Ugandan studies, we did not find any effects of the SLCO1B1 or other genotypes tested on rifampicin PK. However, our findings are in keeping with more recent studies from Malawi and India emphasizing the need for geographically diverse and adequately powered studies. The clinical relevance of the low tuberculosis drug concentrations warrants further investigation.

Keywords: rifampicin, isoniazid pharmacokinetics, genetics, NAT2, SLCO1B1, tuberculosis

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Authors: Nouri, K., Ghassem Alaskari, M., K., Amiri Hazaveh, A., Nabi Bidhendi, M.

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Pore pressure is one on the key Petrophysical parameter in exploration discussion and survey on hydrocarbon reservoir. Determination of pore pressure in various levels of drilling and integrity of drilling mud and high pressure zones in order to restrict blow-out and following damages are significant. The pore pressure is obtained by seismic and well logging data. In this study the pore pressure and over burden pressure through the matrix stress and Tarzaqi equation and other related formulas are calculated. By making a comparison on variation of density log in over normal pressure zones with change of sonic impedance under influence of compressional, shear, and Stonely waves, the correlation level of sonic impedance with density log is studied. The level of correlation and variation trend is recorded in sonic impedance under influence Stonely wave with density log that key factor in recording of over burden pressure and pore pressure in Tarzaqi equation is high. The transition time is in divert relation with porosity and fluid type in the formation and as a consequence to the pore pressure. The density log is a key factor in determination of pore pressure therefore sonic impedance under Stonley wave is denotes well the identification of high pressure besides other used factors.

Keywords: pore pressure, stonely wave, density log, sonic impedance, high pressure zone

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Authors: Martin Juhas, Bohuslava Juhasova, Igor Halenar, Andrej Elias

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This article deals with the possibility of increasing efficiency, reliability and safety of the system for teledosimetric data collection management and their evaluation as a part of complex study for activity “Research of data collection, their measurement and evaluation with mobile and autonomous units” within project “Research of monitoring and evaluation of non-standard conditions in the area of nuclear power plants”. Possible weaknesses in existing system are identified. A study of available cluster solutions with possibility of their deploying to analysed system is presented.

Keywords: teledosimetric data, efficiency, reliability, safety, cluster solution

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Authors: Zainal Arifin, Mohammad Saeri

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The purpose of this study is to determine the efficiency of irrigation use on the growth and yield of two varieties of rice. Water management research on rainfed lowland rice was carried out in dry season (DS I) 2016 in an area of 10,000 m2 in Bunbarat Village, Rubaru Subdistrict, Sumenep Regency. The research was randomized block design factorial with 8 treatments and repeated 3 times, ie Factor I (varieties): (a) Inpago 9, and (b) Sidenuk; factor II (irrigation): (a) Alternate Wetting and Drying, (b) intermittent, (c) submerged, and (d) inundated. The results showed that dominant weed species such as purslane (Portulaca oleraceae L.) and barnyard grass (Echinochloa crusgalli) were mostly found in rice cultivation with Alternate Wetting and Drying, intermittent and submerged irrigation treatment, while the lowest was inundated irrigation. The use of Sidenuk variety with Alternate Wetting and Drying irrigation yielded 5.7 t/ha dry grain harvest (dgh) and was not significantly different from the inundated watering using the Sidenuk variety (6.2 t/ha dgh). With Alternate Wetting and Drying irrigation technique, water use is more efficient as much as 1,503 m3/ha so as to produce 1 kg of grain, it needs 459 liters of water compared to inundated irrigation (665 liters/kg of grain). Results of analysis of rice farming Sidenuk variety with Alternate Wetting and Drying irrigation has the highest B/C ratio (2.56) so that economically feasible.

Keywords: water management, varieties, rice, dry season, rainfed lowland

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Authors: R. Noorani, K. Peerless, J. Mandrell, A. Lopez, R. Dalberto, M. Alzebaq

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Rapid prototyping (RP) is an additive manufacturing technology used in industry that works by systematically depositing layers of working material to construct larger, computer-modeled parts. A key challenge associated with this technology is that RP parts often feature undesirable levels of surface roughness for certain applications. To combat this phenomenon, an experimental technique called Design of Experiments (DOE) can be employed during the growth procedure to statistically analyze which RP growth parameters are most influential to part surface roughness. Utilizing DOE to identify such factors is important because it is a technique that can be used to optimize a manufacturing process, which saves time, money, and increases product quality. In this study, a four-factor/two level DOE experiment was performed to investigate the effect of temperature, layer thickness, infill percentage, and infill speed on the surface roughness of RP prototypes. Samples were grown using the sixteen different possible growth combinations associated with a four-factor/two level study, and then the surface roughness data was gathered for each set of factors. After applying DOE statistical analysis to these data, it was determined that layer thickness played the most significant role in the prototype surface roughness.

Keywords: rapid prototyping, surface roughness, design of experiments, statistical analysis, factors and levels

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Authors: Tahsin Shameem, Chowdhury Sadman Jahan, Mohammad Alam

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Interest about Net Zero Energy Buildings have gained traction in recent years following the need to sustain energy consumption with generations on site and to reduce dependence on grid supplied energy from large plants using fossil fuel. With this end in view, building integrated photovoltaics are being studied attempting to utilize all exterior facades of a building to generate power. In this paper, we have looked at the physical parameters defining a dye sensitized solar cell (DSSC) and discussed their impact on energy harvest. Following our discussion and experimental data obtained from literature, we have attempted to optimize these physical parameters accordingly so as to allow maximum light absorption for a given active layer thickness. We then modified a planer DSSC design with our optimized properties to allow adequate light transmission which demonstrated a high fill factor and an External Quantum Efficiency (EQE) of greater than 9% by computer aided design and simulation. In conclusion, a DSSC based solar window with such high output values even after such high light transmission through it definitely flags a promising future for this technology and our work elicits the need for further study and practical experimentation.

Keywords: net zero energy building, integrated photovoltaics, dye sensitized solar cell, fill factor, External Quantum Efficiency

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Authors: Marko Živanović, Jovana Bjekić, Maša Vukčević Marković

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Professionals and volunteers involved in refugee protection and support are on a daily basis faced with people who have experienced numerous traumatic experiences and, as such, are subjected to secondary traumatization (ST). The aim of this study was to provide insight into risk factors for ST in helpers working with refugees in Serbia. A total of 175 participants working with refugees fulfilled: Secondary Traumatization Questionnaire, checklist of refugees’ traumatic experiences, Hopkins Symptoms Checklist (HSCL) assessing depression and anxiety symptoms, quality of life questionnaire (MANSA), HEXACO personality inventory, and COPE assessing coping mechanisms. In addition, participants provided information on work-related problems. Qualitative analysis of answers to the question about most difficult part of their job has shown that burnout-related issues are clustered around three recurrent topics that can be considered as the most prominent generators of stress, namely: ‘lack of organization and cooperation’, ‘not been able to do enough’, and ‘hard to take it and to process it’. Factor analysis (Maximum likelihood extraction, Promax rotation) have shown that ST comprises of two correlated factors (r = .533, p < .01), namely Psychological deficits and Intrusions. Results have shown that risk factor for ST could be find in three interrelated sources: 1) work-related problems; 2) personality-related risk factors and 3) clients’ traumatic experiences. Among personality related factors, it was shown that risk factor for Intrusions could be find in – high Emotionality (β = .221, p < .05), and Altruism (β = .322, p < .01), while low Extraversion (β = -.365, p < .01) represents risk factor for Psychological deficits. In addition, usage of maladaptive coping mechanisms –mental disengagement (r = .253, p < .01), behavioral disengagement (r = .274, p < .01), focusing on distress and venting of emotions (r = .220, p < .05), denial (r = .164, p < .05), and substance use (r = .232, p < .01) correlate with Psychological deficits while Intrusions corelate with Mental disengagement (r = .251, p < .01) and denial (r = .183, p < .05). Regarding clients’ traumatic experiences it was shown that both quantity of traumatic events in country of origin (for Deficits r = .226, p < .01; for Intrusions r = .174, p < .05) and in transit (for Deficits r = .288, p < .01), as well as certain content-related features of such experiences (especially experiences which are severely dislocated from ‘everyday reality’) are related to ST. In addition, Psychological deficits and Intrusions have shown to be accompanied by symptoms of depression (r = .760, p < .01; r = .552, p < .01) and anxiety (r = .740, p < .01; r = .447, p < .01) and overall lower life quality (r = -.454, p < .01; r = .256, p < .01). Results indicate that psychological vulnerability of persons who are working with traumatized individuals can be found in certain personality traits, and usage of maladaptive coping mechanisms, which disable one to deal with work-related issues, and to cope with quantity and quality of traumatic experiences they were faced with, affecting ones’ psychological well-being. Acknowledgement: This research was funded by IRC Serbia.

Keywords: mental health, refugees, secondary traumatization, traumatic experiences

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Authors: Rida Kanwal, Wang Yuhui, Song Weiguo

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Wildfires are one of the most prominent threats to ecosystems, human health, and economic activities, with wind acting as a critical driving factor. This study combines machine learning (ML) and remote sensing (RS) to assess the effects of wind on wildfires in Chongqing Province from August 16-23, 2022. Landsat 8 satellite images were used to estimate the difference normalized burn ratio (dNBR), representing prefire and postfire vegetation conditions. Wind data was analyzed through geographic information system (GIS) mapping. Correlation analysis between wind speed and fire radiative power (FRP) revealed a significant relationship. An autoregressive integrated moving average (ARIMA) model was developed for wind forecasting, and linear regression was applied to determine the effect of wind speed on FRP. The results identified high wind speed as a key factor contributing to the surge in FRP. Wind-rose plots showed winds blowing to the northwest (NW), aligning with the wildfire spread. This model was further validated with data from other provinces across China. This study integrated ML, RS, and GIS to analyze wildfire behavior, providing effective strategies for prediction and management.

Keywords: wildfires, machine learning, remote sensing, wind speed, GIS, wildfire behavior

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Authors: Mastaneh Safarnejad Shad, Wim Dehaen, Steven De Jonghe

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Since CXCR4 is the main coreceptor of HIV-1 and plays an important role in human immunodeficiency virus (HIV) entry, numerous efforts were directed towards the discovery of new classes of small molecules that act as CXCR4 antagonists. In addition, CXCR4 antagonists are potentially useful in the treatment of several other disorders, such as cancer cell metastasis, leukemia cell proliferation, rheumatoid arthritis, and pulmonary fibrosis. Since AMD3100 (plerixafor) is the only CXCR4 antagonist which obtained approval by the Food and Drug Administration (FDA), we were motivated to investigate a new category of molecules as CXCR4 antagonists. Most of the scaffolds which have been studied so far as CXCR4 antagonists are based on the tetrahydroquinoline (THQ) moiety in which AMD11070 (mavorixafor), GSK-812394, and TIQ15 displayed the most potent CXCR4 antagonism. Due to the high potency of these scaffolds, two different series of compounds were prepared in this work. In the first set, the THQ moiety is coupled to an amine chain and various isoquinoline derivatives (prepared by an in-house developed triazolization strategy), of which the upper part of molecules is identical to AMD11070 and TIQ15. In the second category of compounds, the THQ moiety was simplified by the synthesis of a substituted pyridine moiety. In order to investigate if CXCR4 antagonism requires the presence of an isoquinoline moiety, the corresponding pyridine analogues were also prepared. In both series of compounds, potent CXCR4 antagonism was noticed.

Keywords: CXCR4 coreceptor, CXCR4 antagonists, HIV inhibitor, tetrahydroquinoline

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Authors: Kyung Min Kwom, Young Joo Lee

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Purpose: Up to 90% of pancreatic cancer patient suffer from neuropathic pain. In palliative care setting, pain control in a pancreatic cancer patient is one of the major goals. Ketamine is a NMDA receptor antagonist effective in neuropathic pain. Also, there have been studies about opioid sparing effect of ketamine. This study was held in palliative care unit among pancreatic cancer patients to find out the factors related to ketamine use and the opioid sparing effect. Methods: Medical records of pancreatic cancer patients admitted to St. Mary’s hospital palliative care unit from 2013.1 to 2014.12 were reviewed. Patients were divided into two categories according to ketamine use. Also, opioid use before and after ketamine use was compared in ketamine group. Results: Compared to non ketamine use group, patients in ketamine group required a higher dose of opioid. Total opioid dose, daily opioid dose, number of daily rescue medication, daily average rescue dose were statistically significantly higher in ketamine group. Opioid requirement was increased after ketamine administration. Conclusion: In this study, ketamine group required more opioid. Ketamine is frequently considered in patients with severe pain, requiring high amount of opioid. Also, ketamine did not have an opioid sparing effect. Future studies about palliative use of ketamine in a larger number of patients are required.

Keywords: ketamine, opioid sparing, palliative care, pancreatic cancer

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Authors: Jannes Quer, Amir Niknejad, Marcus Weber

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Computational Drug Design is often based on Molecular Dynamics simulations of molecular systems. Molecular Dynamics can be used to simulate, e.g., the binding and unbinding event of a small drug-like molecule with regard to the active site of an enzyme or a receptor. However, the time-scale of the overall binding event is many orders of magnitude longer than the time-scale of simulation. Thus, there is a need to speed-up molecular simulations. In order to speed up simulations, the molecular dynamics trajectories have to be ”steared” out of local minimizers of the potential energy surface – the so-called metastabilities – of the molecular system. Increasing the kinetic energy (temperature) is one possibility to accelerate simulated processes. However, with temperature the entropy of the molecular system increases, too. But this kind ”stearing” is not directed enough to stear the molecule out of the minimum toward the saddle point. In this article, we give a new mathematical idea, how a potential energy surface can be changed in such a way, that entropy is kept under control while the trajectories are still steared out of the metastabilities. In order to compute the unsteared transition behaviour based on a steared simulation, we propose to use extrapolation methods. In the end we mathematically show, that our method accelerates the simulations along the direction, in which the curvature of the potential energy surface changes the most, i.e., from local minimizers towards saddle points.

Keywords: extrapolation, Eyring-Kramers, metastability, multilevel sampling

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Authors: Sarah Elsayed Mohammed, Lamiaa Ahmed Ahmed, Mahmoud Mohammed Khattab

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Aim: The aim of the present study was to investigate whether combined nicorandil and bone marrow-derived mesenchymal stem cells (BMDMSC) treatment could offer an additional benefit in ameliorating isoproterenol (ISO)-induced heart failure in rats. Methods: ISO (85 and 170 mg/kg/day) was injected subcutaneously for 2 successive days, respectively. By day 3, electrocardiographic changes were recorded and serum was separated for determination of CK-MB level for confirmation of myocardial damage. Nicorandil (3 mg/kg/day) was then given orally with or without a single i.v. BMDMSC administration. Electrocardiography and echocardiography were recorded 2 weeks after beginning of treatment. Rats were then sacrificed and ventricles were isolated for estimation of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-α) and transforming growth factor-beta (TGF-β) contents, caspase-3 activity as well as inducible nitric oxide synthase (iNOS) and connexin-43 protein expressions. Moreover, histological analysis of myocardial fibrosis was performed and cryosections were done for estimation of homing of BMDMSC. Results: ISO induced a significant increase in ventricles/body weight ratio, left ventricular end diastolic (LVEDD) and systolic dimensions (LVESD), ST segment and QRS duration. Moreover, myocardial fibrosis as well as VEGF, TNF-α and TGF-β contents were significantly increased. On the other hand, connexin-43 protein expression was significantly decreased, while caspase-3 and iNOS protein expressions were significantly increased. Combined therapy provided additional improvement compared to cell treatment alone towards reducing cardiac hypertrophy, fibrosis and inflammation. Furthermore, combined therapy induced significant increase in angiogenesis and BMDMSC homing and prevented ISO induced changes in iNOS, connexin-43 and caspase-3 protein expressions. Conclusion: Combined nicorandil/BMDMSC treatment was superior to BMDMSC alone towards preventing ISO-induced heart failure in rats.

Keywords: fibrosis, isoproterenol, mesenchymal stem cells, nicorandil

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Authors: Ali Alavi, Owen Nguyen, Jiangang Fei, Jafar Sayareh

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The main purpose of this research is to propose a conceptual framework to analyze port logistics integration in general and for the Iranian port sector in particular, including consideration of the challenges, outcomes, and opportunities in implementing port logistics integration. First, a literature review of studies on logistics integration in seaports and terminals is conducted. Second, a new conceptual framework for port logistics integration is proposed to incorporate the role of the new variables emerging from the recent developments in the global business environment. The literature review has found the logistics process and operations, information integration, value-added services, and logistics practices, organizational activities, resource sharing and institutional support being influential to logistics integration. The study used survey method to test the proposed conceptual framework. Both online and self-administrative survey have been used to collect data from ‎port official staffs in Iranian seaports and their associations (internal port ‎stakeholders) as well ‎as other experts in various actors. In the study, the questionnaire was first validated using exploratory factor analysis (EFA) and then by confirmatory factor analysis (CFA). The results of the EFA and CFA confirmed the finding from the literature review. Research results and conceptual framework shed the lights on port logistics integration concept and suggest guidelines and procedures improve port logistics integration.

Keywords: maritime logistics, logistics integration, port management, EFA, CFA

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Authors: S. Ghammamy, M. Mirzaabdollahiha

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Quantum mechanical calculations of energies, geometries, and vibrational wavenumbers of fluorous 1,3-dion compounds are carried out using density functional theory (DFT/B3LYP) method with LANL2DZ basis sets. The calculated HOMO and LUMO energies show that charge transfer occurs in the molecules. The thermodynamic functions of fluorous 1,3-dion compounds have been performed at B3LYP/LANL2DZ basis sets. The theoretical spectrograms for F NMR spectra of fluorous 1,3-dion compounds have also been constructed. The F NMR nuclear shieldings of fluoride ligands in fluorous 1,3-dion compounds have been studied quantum chemical.

Keywords: density function theory, natural bond orbital, HOMO, LOMO, fluorous

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Authors: Mohamad Najari, Gilbert Grondin, Marwan El-Rich

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Design trucks in standard codes are selected based on the amount of damage they cause on structures-specifically bridges- and roads to represent the real traffic loads. Some limited numbers of trucks are run on a bridge one at a time and the damage on the bridge is recorded for each truck. One design track is also run on the same bridge “n” times -“n” is the number of trucks used previously- to calculate the damage of the design truck on the same bridge. To make these damages equal a reduction factor is needed for that specific design truck in the codes. As the limited number of trucks cannot be the exact representative of real traffic through the life of the structure, these reduction factors are not accurately calculated and they should be modified accordingly. Started on July 2004, the vehicle load data were collected in six weigh in motion (WIM) sites owned by Alberta Transportation for eight consecutive years. This database includes more than 200 million trucks. Having these data gives the opportunity to compare the effect of any standard fatigue trucks weigh and the real traffic load on the fatigue life of the bridges which leads to a modification for the fatigue truck factor in the code. To calculate the damage for each truck, the truck is run on the bridge, moment history of the detail under study is recorded, stress range cycles are counted, and then damage is calculated using available S-N curves. A 2000 lines FORTRAN code has been developed to perform the analysis and calculate the damages of the trucks in the database for all eight fatigue categories according to Canadian Institute of Steel Construction (CSA S-16). Stress cycles are counted using rain flow counting method. The modification factors for design truck (CL-625) are calculated for two different bridge configurations and ten span lengths varying from 1 m to 200 m. The two considered bridge configurations are single-span bridge and four span bridge. This was found to be sufficient and representative for a simply supported span, positive moment in end spans of bridges with two or more spans, positive moment in interior spans of three or more spans, and the negative moment at an interior support of multi-span bridges. The moment history of the mid span is recorded for single-span bridge and, exterior positive moment, interior positive moment, and support negative moment are recorded for four span bridge. The influence lines are expressed by a polynomial expression obtained from a regression analysis of the influence lines obtained from SAP2000. It is found that for design truck (CL-625) fatigue truck factor is varying from 0.35 to 0.55 depending on span lengths and bridge configuration. The detail results will be presented in the upcoming papers. This code can be used for any design trucks available in standard codes.

Keywords: bridge, fatigue, fatigue design truck, rain flow analysis, FORTRAN

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Authors: Phutthiwat Waiyawuththanapoom

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This study has only one objective which is to identify the different in factors of choosing the distributor for food and non-food OTOP entrepreneur in Thailand. In this research, the types of OTOP product will be divided into two groups which are food and non-food. The sample for the food type OTOP product was the processed fruit and vegetable from Nakorn Pathom province and the sample for the non-food type OTOP product was the court doll from Ang Thong province. The research was divided into 3 parts which were a study of the distribution pattern and how to choose the distributor of the food type OTOP product, a study of the distribution pattern and how to choose the distributor of the non-food type OTOP product and a comparison between 2 types of products to find the differentiation in the factor of choosing distributor. The data and information was collected by using the interview. The populations in the research were 5 producers of the processed fruit and vegetable from Nakorn Pathom province and 5 producers of the court doll from Ang Thong province. The significant factor in choosing the distributor of the food type OTOP product is the material handling efficiency and on-time delivery but for the non-food type OTOP product is focused on the channel of distribution and cost of the distributor.

Keywords: distributor, OTOP, food and non-food, selection

Procedia PDF Downloads 355