Search results for: triple negative breast cancer
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 6994

Search results for: triple negative breast cancer

5074 Large Herbivores Benefit Plant Growth via Diverse and Indirect Pathways in a Temperate Grassland

Authors: Xiaofei Li, Zhiwei Zhong, Deli Wang

Abstract:

Large herbivores affect plant growth not only through their direct, consumptive effects, but also through indirect effects that alter species interactions. Indirect effects can be either positive or negative, therefore having the potential to mitigate or enhance the direct impacts of herbivores. However, until recently, we know considerably less about the indirect effects than the direct effects of large herbivores on plants, and few studies have explored multiple indirect pathways simultaneously. Here, we investigated how large domestic herbivores, cattle (Bos taurus), can shape population growth of an intermediately preferred forb species, Artemsisa scoparia, through diverse pathways in a temperate grassland of northeast China. We found that, although exposure to direct consumption of cattle, A. scoparia growth was not inhibited, but rather showed a significant increase in the grazed than ungrazed areas. This unexpected result was due to grazing-induced multiple indirect, positive effects overwhelmed the direct, negative consumption effects of cattle on plant growth. The much more intensive consumption on the dominant Leymus chinensis grass, ground litter removal, and increases in ant nest abundance induced by cattle, exerted significant indirect, positive effects on A. scoparia growth. These pathways benefited A.scoparia growth by lessening interspecific competition, mitigating negative effects of litter accumulation, and increasing soil nutrient availability, respectively. Our results highlight the need to integrate indirect effects into the traditional food web theory, which is based primary on direct, trophic linkages, to fully understand community organization and dynamics. Large herbivores are important conservation and management targets, our results suggest that these mammals should be managed with the understanding that they can affect primary producers through diverse paths.

Keywords: grasslands, large herbivores, plant growth, indirect effects

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5073 Depression and Suicide Risk among HIV/AIDS Positive Individuals Attending an Out Patient HIV/AIDS Clinic in a Nigerian Tertiary Health Institution

Authors: Onyebueke Godwin, Okwarafor Friday

Abstract:

Introduction: Persons with HIV/AIDS disease are predisposed to mental health disorders such as depression and suicide. HIV/AIDS, being a chronic medical illness with antecedent stigmatization ostracization, leads to low mood, low self-esteem, and a tendency to kill oneself due to the burden of the disease in terms of cost and disability. The aim of one study was to examine the prevalence of depression and risk of suicide among HIV/AIDS patients compared to negative persons. Instruments: The Major Depressive Episode and Suicidality modules of the MINI-Neuropsychiatric inventory were used to screen the attendees. Report: The prevalence of depression and risk of suicide were 27.8% and 7.8%, respectively, for the HIV positive subjects, but 1208% and 2.2%, respectively, for negative subjects. Conclusion and Significance: Persons with HIV/AIDS usually present with mental health symptoms, but the attending physicians usually pay attention to physical symptoms. The symptoms of the disease or the side effects of the medication may mask the mental health disease. Recommendation: There is need to screen HIV/AIDS patents for mental health disorders during clinic visits.

Keywords: depression, HIV/AIDS, suicidality

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5072 Knowledge and Attitude towards Helicobacter pylori: Awareness about Health Impacts of H. pylori Gastric Ulcer and Its Carcinogenic Potential among Adults in Sharjah

Authors: Abdullah Malek, Muzn Al Khaldi, Lian Odeh, Atheer Tariq, Mohammad Al Fardan, Hiba Barqawi

Abstract:

H. pylori bacterium is a known underlying agent for gastritis, peptic ulcer disease, and gastric cancer and is believed to infect half of the world’s population. Even with the ubiquity of H. pylori bacterium, there is lack of knowledge regarding its modes of transmission, associated diseases, carcinogenic effect and means of prevention; especially in the UAE. A cross sectional study of 500 participants, of which 58% (n= 289) of the respondents were female, and 42% (n=210) were male, was conducted in Sharjah to assess the knowledge, and explore the attitudes and practices among UAE residents towards Helicobacter Pylori and its associated PUD as well as its carcinogenic nature. A structured self-administered questionnaire was distributed to the target population to establish their demographic background and selected aspects of their lifestyle. General knowledge about H. Pylori was poor, only 24.6% stated they have heard of H. pylori. Attitudes towards prevention and practices were relatively poor as well. Subjects who suffered from severe symptoms (ALARM symptoms) had significantly lower habit scores than those with mild and moderate symptoms (p=0.0078**). To the authours’ knowledge, no previous studies were conducted in the United Arab Emirates regarding the epidemiology of the infection to detect the extent of H. Pylori’s impact on the public health. The results of this study can be used to draw conclusions about the average knowledge of the UAE population regarding H. pylori. It can also be a starting point to devise new education programs and campaigns that raise awareness of this health issue which could be easily avoided with early diagnosis and antibiotic treatment.

Keywords: chronic gastritis, community health, gastric cancer, Helicobacter pylori, peptic ulcers

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5071 Non-Melanoma Skin Cancer of Cephalic Extremity – Clinical and Histological Aspects

Authors: Razvan Mercut, Mihaela Ionescu, Vlad Parvanescu, Razvan Ghita, Tudor-Gabriel Caragea, Cristina Simionescu, Marius-Eugen Ciurea

Abstract:

Introduction: Over the past years, the incidence of non-melanoma skin cancer (NMSC) has continuously increased, being one of the most commonly diagnosed carcinomasofthe cephalic extremity. NMSC regroups basal cell carcinoma (BCC), squamous cell carcinoma (SCC), Merkel cell carcinoma, cutaneous lymphoma, and sarcoma. The most common forms are BCC and SCC, both still implying a significant level of morbidity due to local invasion (especially BCC), even if the overall death rates are declining. The objective of our study was the evaluation of clinical and histological aspects of NMSC for a group of patients with BCC and SCC, from Craiova, a south-western major city in Romania. Materialand method: Our study lot comprised 65 patients, with an almost equal distribution of sexes, and ages between 23-91 years old (mean value±standard deviation62.61±16.67), all treated within the Clinic of Plastic Surgery and Reconstructive Microsurgery, Clinical Emergency County Hospital Craiova, Romania, between 2019-2020. In order to determine the main morphological characteristics of both studied cancers, we used paraffin embedding techniques, with various staining methods:hematoxylin-eosin, Masson's trichrome stain with aniline blue, and Periodic acid-schiffAlcian Blue. The statistical study was completed using Microsoft Excel (Microsoft Corp., Redmond, WA, USA), with XLSTAT (Addinsoft SARL, Paris, France). Results: The overall results of our study indicate that BCC accounts for 67.69% of all NMSC forms; SCC covers 27.69%, while 4.62% are representedby other forms. The most frequent site is the nose for BCC (27.69%, 18 patients), being followed by preauricular regions, forehead, and periorbital areas. For patients with SCC, tumors were mainly located at lips level (66.67%, 12 patients). The analysis of NMSC histological forms indicated that nodular BCC is predominant (45.45%, 20 patients), as well as ulcero-vegetant SCC (38.89%, 7 patients). We have not identified any topographic characteristics or NMSC forms significantly related to age or sex. Conclusions: The most frequent NMSC form identified for our study lot was BCC. The preferred location was the nose for BCC. For SCC, the oral cavity is the most frequent anatomical site, especially the lips level. Nodular BCC and ulcero-vegetant SCC were the most commonly identified histological types. Our findings emphasize the need for periodic screening, in order to improve prevention and early treatment for these malignancies.

Keywords: non-melanoma skin cancer, basal cell carcinoma, squamous cell carcinoma, histological

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5070 Creating Bridges: The Importance of Intergenerational Experiences in the Educational Context

Authors: A. Eiguren-Munitis, N. Berasategi, J. M. Correa

Abstract:

Changes in family structures, immigration, economic crisis, among others, hinder the connection between different generations. This situation gives rise to a greater lack of social protection of the groups in vulnerable situations, such as the elderly and children. There is a growing need to search for shared spaces where different generations manage to break negative stereotypes and interact with each other. The school environment provides a favourable context in which the approach of different generations can be worked on. The intergenerational experiences that take place within the school context help to introduce the educational ideology for a lifetime. This induces bilateral learning, which encourages citizen participation. For this reason, the general objective of this research is to deepen the impact that intergenerational experiences have on participating students. The research is carried out based on mixed methods. The qualitative and quantitative evaluation included pre-test and post-test questionnaires (n=148) and group interviews (n=43). The results indicate that the intergenerational experiences influence different levels, on the one hand, help to promote school motivation and on the other hand, help to reduce negative stereotypes towards older people thus contributing to greater social cohesion.

Keywords: intergenerational learning, school, stereotypes, social cohesion

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5069 Evaluation of Antibiotic Resistance and Extended-Spectrum β-Lactamases Production Rates of Gram Negative Rods in a University Research and Practice Hospital, 2012-2015

Authors: Recep Kesli, Cengiz Demir, Onur Turkyilmaz, Hayriye Tokay

Abstract:

Objective: Gram-negative rods are a large group of bacteria, and include many families, genera, and species. Most clinical isolates belong to the family Enterobacteriaceae. Resistance due to the production of extended-spectrum β-lactamases (ESBLs) is a difficulty in the handling of Enterobacteriaceae infections, but other mechanisms of resistance are also emerging, leading to multidrug resistance and threatening to create panresistant species. We aimed in this study to evaluate resistance rates of Gram-negative rods bacteria isolated from clinical specimens in Microbiology Laboratory, Afyon Kocatepe University, ANS Research and Practice Hospital, between October 2012 and September 2015. Methods: The Gram-negative rods strains were identified by conventional methods and VITEK 2 automated identification system (bio-Mérieux, Marcy l’etoile, France). Antibiotic resistance tests were performed by both the Kirby-Bauer disk-diffusion and automated Antimicrobial Susceptibility Testing (AST, bio-Mérieux, Marcy l’etoile, France) methods. Disk diffusion results were evaluated according to the standards of Clinical and Laboratory Standards Institute (CLSI). Results: Of the totally isolated 1.701 Enterobacteriaceae strains 1434 (84,3%) were Klebsiella pneumoniae, 171 (10%) were Enterobacter spp., 96 (5.6%) were Proteus spp., and 639 Nonfermenting gram negatives, 477 (74.6%) were identified as Pseudomonas aeruginosa, 135 (21.1%) were Acinetobacter baumannii and 27 (4.3%) were Stenotrophomonas maltophilia. The ESBL positivity rate of the totally studied Enterobacteriaceae group were 30.4%. Antibiotic resistance rates for Klebsiella pneumoniae were as follows: amikacin 30.4%, gentamicin 40.1%, ampicillin-sulbactam 64.5%, cefepime 56.7%, cefoxitin 35.3%, ceftazidime 66.8%, ciprofloxacin 65.2%, ertapenem 22.8%, imipenem 20.5%, meropenem 20.5 %, and trimethoprim-sulfamethoxazole 50.1%, and for 114 Enterobacter spp were detected as; amikacin 26.3%, gentamicin 31.5%, cefepime 26.3%, ceftazidime 61.4%, ciprofloxacin 8.7%, ertapenem 8.7%, imipenem 12.2%, meropenem 12.2%, and trimethoprim-sulfamethoxazole 19.2 %. Resistance rates for Proteus spp. were: 24,3% meropenem, 26.2% imipenem, 20.2% amikacin 10.5% cefepim, 33.3% ciprofloxacin and levofloxacine, 31.6% ceftazidime, 20% ceftriaxone, 15.2% gentamicin, 26.6% amoxicillin-clavulanate, and 26.2% trimethoprim-sulfamethoxale. Resistance rates of P. aeruginosa was found as follows: Amikacin 32%, gentamicin 42 %, imipenem 43%, merpenem 43%, ciprofloxacin 50%, levofloxacin 52%, cefepim 38%, ceftazidim 63%, piperacillin/tacobactam 85%, for Acinetobacter baumannii; Amikacin 53.3%, gentamicin 56.6 %, imipenem 83%, merpenem 86%, ciprofloxacin 100%, ceftazidim 100%, piperacillin/tacobactam 85 %, colisitn 0 %, and for S. malthophilia; levofloxacin 66.6 % and trimethoprim/sulfamethoxozole 0 %. Conclusions: This study showed that resistance in Gram-negative rods was a serious clinical problem in our hospital and suggested the need to perform typification of the isolated bacteria with susceptibility testing regularly in the routine laboratory procedures. This application guided to empirical antibiotic treatment choices truly, as a consequence of the reality that each hospital shows different resistance profiles.

Keywords: antibiotic resistance, gram negative rods, ESBL, VITEK 2

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5068 A Comparative Time-Series Analysis and Deep Learning Projection of Innate Radon Gas Risk in Canadian and Swedish Residential Buildings

Authors: Selim M. Khan, Dustin D. Pearson, Tryggve Rönnqvist, Markus E. Nielsen, Joshua M. Taron, Aaron A. Goodarzi

Abstract:

Accumulation of radioactive radon gas in indoor air poses a serious risk to human health by increasing the lifetime risk of lung cancer and is classified by IARC as a category one carcinogen. Radon exposure risks are a function of geologic, geographic, design, and human behavioural variables and can change over time. Using time series and deep machine learning modelling, we analyzed long-term radon test outcomes as a function of building metrics from 25,489 Canadian and 38,596 Swedish residential properties constructed between 1945 to 2020. While Canadian and Swedish properties built between 1970 and 1980 are comparable (96–103 Bq/m³), innate radon risks subsequently diverge, rising in Canada and falling in Sweden such that 21st Century Canadian houses show 467% greater average radon (131 Bq/m³) relative to Swedish equivalents (28 Bq/m³). These trends are consistent across housing types and regions within each country. The introduction of energy efficiency measures within Canadian and Swedish building codes coincided with opposing radon level trajectories in each nation. Deep machine learning modelling predicts that, without intervention, average Canadian residential radon levels will increase to 176 Bq/m³ by 2050, emphasizing the importance and urgency of future building code intervention to achieve systemic radon reduction in Canada.

Keywords: radon health risk, time-series, deep machine learning, lung cancer, Canada, Sweden

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5067 Characterization of Herberine Hydrochloride Nanoparticles

Authors: Bao-Fang Wen, Meng-Na Dai, Gao-Pei Zhu, Chen-Xi Zhang, Jing Sun, Xun-Bao Yin, Yu-Han Zhao, Hong-Wei Sun, Wei-Fen Zhang

Abstract:

A drug-loaded nanoparticles containing berberine hydrochloride (BH/FA-CTS-NPs) was prepared. The physicochemical characterizations of BH/FA-CTS-NPs and the inhibitory effect on the HeLa cells were investigated. Folic acid-conjugated chitosan (FA-CTS) was prepared by amino reaction of folic acid active ester and chitosan molecules; BH/FA-CTS-NPs were prepared using ionic cross-linking technique with BH as a model drug. The morphology and particle size were determined by Transmission Electron Microscope (TEM). The average diameters and polydispersity index (PDI) were evaluated by Dynamic Light Scattering (DLS). The interaction between various components and the nanocomplex were characterized by Fourier Transform Infrared Spectroscopy (FT-IR). The entrapment efficiency (EE), drug-loading (DL) and in vitro release were studied by UV spectrophotometer. The effect of cell anti-migratory and anti-invasive actions of BH/FA-CTS-NPs were investigated using MTT assays, wound healing assays, Annexin-V-FITC single staining assays, and flow cytometry, respectively. HeLa nude mice subcutaneously transplanted tumor model was established and treated with different drugs to observe the effect of BH/FA-CTS-NPs in vivo on HeLa bearing tumor. The BH/FA-CTS-NPs prepared in this experiment have a regular shape, uniform particle size, and no aggregation phenomenon. The results of DLS showed that mean particle size, PDI and Zeta potential of BH/FA-CTS NPs were (249.2 ± 3.6) nm, 0.129 ± 0.09, 33.6 ± 2.09, respectively, and the average diameter and PDI were stable in 90 days. The results of FT-IR demonstrated that the characteristic peaks of FA-CTS and BH/FA-CTS-NPs confirmed that FA-CTS cross-linked successfully and BH was encapsulated in NPs. The EE and DL amount were (79.3 ± 3.12) % and (7.24 ± 1.41) %, respectively. The results of in vitro release study indicated that the cumulative release of BH/FA-CTS NPs was (89.48±2.81) % in phosphate-buffered saline (PBS, pH 7.4) within 48h; these results by MTT assays and wund healing assays indicated that BH/FA-CTS NPs not only inhibited the proliferation of HeLa cells in a concentration and time-dependent manner but can induce apoptosis as well. The subcutaneous xenograft tumor formation rate of human cervical cancer cell line HeLa in nude mice was 98% after inoculation for 2 weeks. Compared with BH group and BH/CTS-NPs group, the xenograft tumor growth of BH/FA-CTS-NPs group was obviously slower; the result indicated that BH/FA-CTS-NPs could significantly inhibit the growth of HeLa xenograft tumor. BH/FA-CTS NPs with the sustained release effect could be prepared successfully by the ionic crosslinking method. Considering these properties, block proliferation and impairing the migration of the HeLa cell line, BH/FA-CTS NPs could be an important compound for consideration in the treatment of cervical cancer.

Keywords: folic-acid, chitosan, berberine hydrochloride, nanoparticles, cervical cancer

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5066 Development of Nanoparticulate Based Chimeric Drug Delivery System Using Drug Bioconjugated Plant Virus Capsid on Biocompatible Nanoparticles

Authors: Indu Barwal, Shloka Thakur, Subhash C. Yadav

Abstract:

The plant virus capsid protein based nanoparticles are extensively studied for their application in biomedical research for development of nanomedicines and drug delivery systems. We have developed a chimeric drug delivery system by controlled in vitro assembly of separately bioconjugated fluorescent dye (as reporting molecule), folic acid (as receptor binding biomolecule for targeted delivery) and doxorubicin (as anticancer drug) using modified EDC NHS chemistry on heterologously overexpressed (E. coli) capsid proteins of cowpea chlorotic mottle virus (CCMV). This chimeric vehicle was further encapsidated on gold nanoparticles (20nm) coated with 5≠ thiolated DNA probe to neutralize the positive charge of capsid proteins. This facilitates the in vitro assembly of modified capsid subunits on the gold nanoparticles to develop chimeric GNPs encapsidated targeted drug delivery system. The bioconjugation of functionalities, number of functionality on capsid subunits as well as virus like nanoparticles, structural stability and in vitro assembly were confirmed by SDS PAGE, relative absorbance, MALDI TOF, ESI-MS, Circular dichroism, intrinsic tryptophan fluorescence, zeta particle size analyzer and TEM imaging. This vehicle was stable at pH 4.0 to 8.0 suitable for many organelles targeting. This in vitro assembled chimeric plant virus like particles could be suitable for ideal drug delivery vehicles for subcutaneous cancer treatment and could be further modified for other type of cancer treatment by conjugating other functionalities (targeting, drug) on capsids.

Keywords: chimeric drug delivery vehicles, bioconjugated plant, virus, capsid

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5065 Emotions and Message Sharing on the Chinese Microblog

Authors: Yungeng Xie, Cong Liu, Yi Liu, Xuanao Wan

Abstract:

The study aims to explore microblog users’ emotion expression and sharing behaviors on the Chinese microblog (Weibo). The first theme of study analyzed whether microblog emotions impact readers’ message sharing behaviors, specifically, how the strength of emotion (positive and negative) in microblog messages facilitate/inhibit readers’ sharing behaviors. The second theme compared the differences among the three types of microblog users (i.e., verified enterprise users, verified individual users and unverified users) in terms of their profiles and microblog behaviors. A total of 7114 microblog messages about 24 hot public events in China were sampled from Sina Weibo. The first study results show that strength of negative emotions that microblog messages carry significantly increase the possibility of the message being shared. The second study results indicate that there are significant differences across the three types of users in terms of their emotion expression and its influence on microblog behaviors.

Keywords: emotion expression, information diffusion, microblog, sharing

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5064 Comparison of Meshing Stiffness of Altered Tooth Sum Spur Gear Tooth with Different Pressure Angles

Authors: H. K. Sachidananda, K. Raghunandana, B. Shivamurthy

Abstract:

The estimation of gear tooth stiffness is important for finding the load distribution between the gear teeth when two consecutive sets of teeth are in contact. Based on dynamic model a C-program has been developed to compute mesh stiffness. By using this program position dependent mesh stiffness of spur gear tooth for various profile shifts have been computed for a fixed center distance and altering tooth-sum gearing (100 by ± 4%). It is found that the C-program using dynamic model is one of the rapid soft computing technique which helps in design of gears. The mesh tooth stiffness along the path of contact is studied for both 20° and 25° pressure angle gears at various profile shifts. Better tooth stiffness is noticed in case of negative alteration tooth-sum gears compared to standard and positive alteration tooth-sum gears. Also, in case of negative alteration tooth-sum gearing better mesh stiffness is noticed in 20° pressure angle when compared to 25°.

Keywords: altered tooth-sum gearing, bending fatigue, mesh stiffness, spur gear

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5063 A Shift in the Structure of Economy and Synergy of University: Developing Potential Through Research and Development Center of SMEs in Jember

Authors: Muhamad Nugraha

Abstract:

Economic growth always correlate positively with the magnitude of the unemployment rate. This is caused by labor which one of important variable to keep growth in the real sector of the region. Meanwhile, the economic structure in districts of Jember showed an increase of economic activity began to shift towards the industrial sector and some other economic sectors, so they have an affects to considerations for policy makers to increase economic growth in Jember as an autonomous region in East Java Province. At the fact, SMEs is among the factors driving economic growth in the region. This is shown by the high amount of SMEs. However, employment in the sector grew slightly slowed. It is caused by a lack of productivity in SMEs. Through the analysis of the transformation of economic structure theory, and the theory of Triple Helix using descriptive analytical method Location Quotient and Shift - Share, found that the results of the economic structure in Jember slowly shifting from the agricultural sector to the industrial sector, because it is dominated by trade sector, hotel and restaurant sector. In addition, SMEs is the potential sector of economic growth in Jember. While to maximizing role and functions of the institution's Research and Development Center of SMEs, there are three points to be known, that are Business Landscape, Business Architecture and Value Added.

Keywords: economic growth, SMEs, labor, Research and Development Center of SMEs

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5062 Recent Climate Variability and Crop Production in the Central Highlands of Ethiopia

Authors: Arragaw Alemayehu, Woldeamlak Bewket

Abstract:

The aim of this study was to understand the influence of current climate variability on crop production in the central highlands of Ethiopia. We used monthly rainfall and temperature data from 132 points each representing a pixel of 10×10 km. The data are reconstructions based on station records and meteorological satellite observations. Production data of the five major crops in the area were collected from the Central Statistical Agency for the period 2004-2013 and for the main cropping season, locally known as Meher. The production data are at the Enumeration Area (EA ) level and hence the best available dataset on crop production. The results show statistically significant decreasing trends in March–May (Belg) rainfall in the area. However, June – September (Kiremt) rainfall showed increasing trends in Efratana Gidim and Menz Gera Meder which the latter is statistically significant. Annual rainfall also showed positive trends in the area except Basona Werana where significant negative trends were observed. On the other hand, maximum and minimum temperatures showed warming trends in the study area. Correlation results have shown that crop production and area of cultivation have positive correlation with rainfall, and negative with temperature. When the trends in crop production are investigated, most crops showed negative trends and below average production was observed. Regression results have shown that rainfall was the most important determinant of crop production in the area. It is concluded that current climate variability has a significant influence on crop production in the area and any unfavorable change in the local climate in the future will have serious implications for household level food security. Efforts to adapt to the ongoing climate change should begin from tackling the current climate variability and take a climate risk management approach.

Keywords: central highlands, climate variability, crop production, Ethiopia, regression, trend

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5061 Computer-Aided Diagnosis System Based on Multiple Quantitative Magnetic Resonance Imaging Features in the Classification of Brain Tumor

Authors: Chih Jou Hsiao, Chung Ming Lo, Li Chun Hsieh

Abstract:

Brain tumor is not the cancer having high incidence rate, but its high mortality rate and poor prognosis still make it as a big concern. On clinical examination, the grading of brain tumors depends on pathological features. However, there are some weak points of histopathological analysis which can cause misgrading. For example, the interpretations can be various without a well-known definition. Furthermore, the heterogeneity of malignant tumors is a challenge to extract meaningful tissues under surgical biopsy. With the development of magnetic resonance imaging (MRI), tumor grading can be accomplished by a noninvasive procedure. To improve the diagnostic accuracy further, this study proposed a computer-aided diagnosis (CAD) system based on MRI features to provide suggestions of tumor grading. Gliomas are the most common type of malignant brain tumors (about 70%). This study collected 34 glioblastomas (GBMs) and 73 lower-grade gliomas (LGGs) from The Cancer Imaging Archive. After defining the region-of-interests in MRI images, multiple quantitative morphological features such as region perimeter, region area, compactness, the mean and standard deviation of the normalized radial length, and moment features were extracted from the tumors for classification. As results, two of five morphological features and three of four image moment features achieved p values of <0.001, and the remaining moment feature had p value <0.05. Performance of the CAD system using the combination of all features achieved the accuracy of 83.18% in classifying the gliomas into LGG and GBM. The sensitivity is 70.59% and the specificity is 89.04%. The proposed system can become a second viewer on clinical examinations for radiologists.

Keywords: brain tumor, computer-aided diagnosis, gliomas, magnetic resonance imaging

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5060 Fiscal Size and Composition Effects on Growth: Empirical Evidence from Asian Economies

Authors: Jeeban Amgain

Abstract:

This paper investigates the impact of the size and composition of government expenditure and tax on GDP per capita growth in 36 Asian economies over the period of 1991-2012. The research employs the technique of panel regression; Fixed Effects and Generalized Method of Moments (GMM) as well as other statistical and descriptive approaches. The finding concludes that the size of government expenditure and tax revenue are generally low in this region. GDP per capita growth is strongly negative in response to Government expenditure, however, no significant relationship can be measured in case of size of taxation although it is positively correlated with economic growth. Panel regression of decomposed fiscal components also shows that the pattern of allocation of expenditure and taxation really matters on growth. Taxes on international trade and property have a significant positive impact on growth. In contrast, a major portion of expenditure, i.e. expenditure on general public services, health and education are found to have significant negative impact on growth, implying that government expenditures are not being productive in the Asian region for some reasons. Comparatively smaller and efficient government size would enhance the growth.

Keywords: government expenditure, tax, GDP per capita growth, composition

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5059 Mechanisms and Regulation of the Bi-directional Motility of Mitotic Kinesin Nano-motors

Authors: Larisa Gheber

Abstract:

Mitosis is an essential process by which duplicated genetic information is transmitted from mother to daughter cells. Incorrect chromosome segregation during mitosis can lead to genetic diseases, chromosome instability and cancer. This process is mediated by a dynamic microtubule-based intracellular structure, the mitotic spindle. One of the major factors that govern the mitotic spindle dynamics are the kinesin-5 biological nano motors that were believed to move unidirectionally on the microtubule filaments, using ATP hydrolysis, thus performing essential functions in mitotic spindle dynamics. Surprisingly, several reports from our and other laboratories have demonstrated that some kinesin-5 motors are bi-directional: they move in minus-end direction on the microtubules as single-molecules and can switch directionality under a number of conditions. These findings broke a twenty-five-years old dogma regarding kinesin directionality (1, 2). The mechanism of this bi-directional motility and its physiological significance remain unclear. To address this unresolved problem, we apply an interdisciplinary approach combining live cell imaging, biophysical single molecule, and structural experiments to examine the activity of these motors and their mutated variants in vivo and in vitro. Our data shows that factors such as protein phosphorylation (3, 4), motor clustering on the microtubules (5, 6) and structural elements (7, 8) regulate the bi-directional motility of kinesin motors. We also show, using Cryo-EM, that bi-directional kinesin motors obtain non-canonical microtubule binding, which is essential to their special motile properties and intracellular functions. We will discuss the implication of these findings to mechanism bi-directional motility and physiological roles in mitosis.

Keywords: mitosis, cancer, kinesin, microtubules, biochemistry, biophysics

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5058 Action Plans to Prevent Negative Attitudes Towards Gay and Lesbian Parents: A Systemic Analysis of Health-Care Interventions in Belgium

Authors: Therese Scali

Abstract:

Over the years, the European Union has continued to extend its action on lesbian, gay men, bisexual and transgender (LGBT) rights to a range of areas including access to justice, asylum, freedom of expression and assembly, parenting, and mutual recognition of civil status within the EU. The European Parliament has been a driving force behind such action adopting a range of resolutions calling for continued progress in this field. In particular, Belgium has been one of the first countries to legalize same-sex parenting and to create a general framework for action against negative attitudes towards gay and lesbian parents. The present paper aims at highlighting public healthcare workers’ attitudes towards different types of same-sex headed families in Belgium, and the content of their interventions in schools. Results revealed that attitudes can go from supportive to unsupportive, and participants do not show the same degree of support towards the different types of same-sex parenting. This contribution highlights work’s implication for public policy by understanding the resources and challenges that health-care professionals face in their work.

Keywords: attitudes, gay and lesbian parents, health-care workers, homophobia, prevention

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5057 Management of Pressure Ulcer with a Locally Constructed Negative Pressure Device (NPD) in Traumatic Paraplegia Patients: A Randomized Controlled Clinical Trial

Authors: Mukesh K. Dwivedi, Rajeshwar N. Srivastava, Amit K. Bhagat, Saloni Raj

Abstract:

Introduction: Management of Pressure Ulcer (PU) is an ongoing clinical challenge particularly in traumatic paraplegia patients in developing countries where socio economic conditions often dictate treatment modalities. When negative pressure wound therapy (NPWT) was introduced, there were a series of devices (V.A.C., KCI, San Antonio, TX) manufactured. These devices for NPWT are costly and hard to afford by patients in developing countries like India. Considering this limitation, this study was planned to design an RCT to compare NPWT by an indigenized locally constructed NPD and conventional gauze dressing for the treatment of PU. Material and Methods: This RCT (CTRI/2014/09/0050) was conducted in the Department of Orthopaedic Surgery at King George’s Medical University (KGMU), India. Thirty-four (34) subjects of traumatic paraplegia having PU of stage 3 or 4, were enrolled and randomized in two treatment groups (NPWT Group & Conventional dressing group). The outcome measures of this study were surface area and depth of PU, exudates, microorganisms and matrix metalloproteinase-8 (MMP-8) during 0 to 9 weeks follow-ups. Levels of MMP-8 were analyzed in the tissues of PU at week 0, 3, 6 and week 9 by Enzyme Linked Immuno Sorbent Assay (ELISA). Results: Significantly reduced length of PU in NPWT group was observed at week 6 (p=0.04) which further reduced at week 9 (p=0.001) as compared to conventionally treated group. Similarly significant reduction of width and depth of PU was observed in NPWT at week 9 (p<0.05). The exudate became significantly (p=0.001) lower in NPWT group as compared with conventionally treated group from 6th to 9th week. Clearance and conversion of slough into red granulation tissue was significantly higher in NPWT group (p=0.001). At week 9, the wound culture was negative in all the subjects of NPWT group, while it was positive in 10 (41⋅6%) subjects of conventional group. Significantly lower level of MMP-8 was observed in subjects of NPWT group at week 6 (0.006**), and continually more reduction was observed at week 9 (<0.0001**) as compared to the conventional group. Conclusion: NPWT by locally constructed NPD is better wound care procedure for management of PU. Our device gave similar results as commercially available devices. Reduction of level of MMP-8 and increased rate of healing was achieved by negative pressure wound therapy (NPWT) as compared to conventional dressing.

Keywords: NPWT, NPD, MMP8, ELISA

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5056 The 'Cornaro Family Tree' as a Tool for Identifying Cornaro Family Portraits

Authors: Rachel Healy

Abstract:

This paper builds on the speaker’s recent identification of an early sixteenth-century painting in the National Gallery of Ireland as containing rare portraits of Giorgio Cornaro (brother of Caterina, Queen of Cyprus) and his son Cardinal Francesco. It resolves similar long-standing confusion regarding the identities of sitters in related works by Titian, Raphael and Bernini, in works such as the Cornaro Triple Portrait in the National Gallery of Art, Washington DC, Man with a Falcon in The Joslyn Art Museum, Omaha, Head of a Cardinal, Wilton House, Wiltshire and The Cornaro Chapel, Santa Maria della Vittoria, Rome, by using an overlooked seventeenth-century painted Cornaro family tree, from Palazzo Corner-Mocenigo, as a tool for identifying these and other sitters in disputed portraits of one of Renaissance Venice’s wealthiest and most influential patrician families. In so doing, it will cast new light on Titian’s development as a portraitist and the extent to which important paintings commissioned by the Cornaro survived fires at two family palaces in Venice in the 1530s. It will also showcase the associations Raphael had with the Cornaro cardinal and will present new evidence relating to the likenesses Bernini fashioned for the Cornaro Chapel in 1647-52.

Keywords: Venice, portraits, titian, genealogy, Bernini, family tree, Raphael, venetian family, cornaro, sixteenth century Venice, portraiture

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5055 Direct Phoenix Identification and Antimicrobial Susceptibility Testing from Positive Blood Culture Broths

Authors: Waad Al Saleemi, Badriya Al Adawi, Zaaima Al Jabri, Sahim Al Ghafri, Jalila Al Hadhramia

Abstract:

Objectives: Using standard lab methods, a positive blood culture requires a minimum of two days (two occasions of overnight incubation) to obtain a final identification (ID) and antimicrobial susceptibility results (AST) report. In this study, we aimed to evaluate the accuracy and precision of identification and antimicrobial susceptibility testing of an alternative method (direct method) that will reduce the turnaround time by 24 hours. This method involves the direct inoculation of positive blood culture broths into the Phoenix system using serum separation tubes (SST). Method: This prospective study included monomicrobial-positive blood cultures obtained from January 2022 to May 2023 in SQUH. Blood cultures containing a mixture of organisms, fungi, or anaerobic organisms were excluded from this study. The result of the new “direct method” under study was compared with the current “standard method” used in the lab. The accuracy and precision were evaluated for the ID and AST using Clinical and Laboratory Standards Institute (CLSI) recommendations. The categorical agreement, essential agreement, and the rates of very major errors (VME), major errors (ME), and minor errors (MIE) for both gram-negative and gram-positive bacteria were calculated. Passing criteria were set according to CLSI. Result: The results of ID and AST were available for a total of 158 isolates. Of 77 isolates of gram-negative bacteria, 71 (92%) were correctly identified at the species level. Of 70 isolates of gram-positive bacteria, 47(67%) isolates were correctly identified. For gram-negative bacteria, the essential agreement of the direct method was ≥92% when compared to the standard method, while the categorical agreement was ≥91% for all tested antibiotics. The precision of ID and AST were noted to be 100% for all tested isolates. For gram-positive bacteria, the essential agreement was >93%, while the categorical agreement was >92% for all tested antibiotics except moxifloxacin. Many antibiotics were noted to have an unacceptable higher rate of very major errors including penicillin, cotrimoxazole, clindamycin, ciprofloxacin, and moxifloxacin. However, no error was observed in the results of vancomycin, linezolid, and daptomycin. Conclusion: The direct method of ID and AST for positive blood cultures using SST is reliable for gram negative bacteria. It will significantly decrease the turnaround time and will facilitate antimicrobial stewardship.

Keywords: bloodstream infection, oman, direct ast, blood culture, rapid identification, antimicrobial susceptibility, phoenix, direct inoculation

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5054 Mathematical Modelling of Blood Flow with Magnetic Nanoparticles as Carrier for Targeted Drug Delivery in a Stenosed Artery

Authors: Sreeparna Majee, G. C. Shit

Abstract:

A study on targeted drug delivery is carried out in an unsteady flow of blood infused with magnetic NPs (nanoparticles) with an aim to understand the flow pattern and nanoparticle aggregation in a diseased arterial segment having stenosis. The magnetic NPs are supervised by the magnetic field which is significant for therapeutic treatment of arterial diseases, tumor and cancer cells and removing blood clots. Coupled thermal energy have also been analyzed by considering dissipation of energy because of the application of the magnetic field and the viscosity of blood. Simulation technique used to solve the mathematical model is vorticity-stream function formulations in the diseased artery. An elevation in SLP (Specific loss power) is noted in the aortic bloodstream when the agglomeration of nanoparticles is higher. This phenomenon has potential application in the treatment of hyperthermia. The study focuses on the lowering of WSS (Wall Shear Stress) with increasing particle concentration at the downstream of the stenosis which depicts the vigorous flow circulation zone. These low shear stress regions prolong the residing time of the nanoparticles carrying drugs which soaks up the LDL (Low Density Lipoprotein) deposition. Moreover, an increase in NP concentration enhances the Nusselt number which marks the increase of heat transfer from the arterial wall to the surrounding tissues to destroy tumor and cancer cells without affecting the healthy cells. The results have a significant influence in the study of medicine, to treat arterial diseases such as atherosclerosis without the need for surgery which can minimize the expenditures on cardiovascular treatments.

Keywords: magnetic nanoparticles, blood flow, atherosclerosis, hyperthermia

Procedia PDF Downloads 141
5053 Manifestation of Behavioral and Emotional Disturbances in News Reporters Covering Traumatic Events

Authors: Misbah Shahzadi

Abstract:

The present study was conducted to identify the emotional and behavioral disturbances among the News Reporters covering Traumatic events. In the present study, a sample of 50 News Reporters belonging to the national and the local news agencies were selected from Rawalpindi and Islamabad who had covered any traumatic event in the past one year. Rotter’s Incomplete Sentence Blank (RISB) and Impact of Event Scale interpretations were used to assess a variety of emotional and behavioral patterns of News Reporters. Results showed that some of the frequent emotional and behavioral reactions exhibited by individuals like withdrawal, anxiety\depression, aggression, hyperarousal and avoidance behavior whereas gender-based comparisons indicated that there is no significant gender difference in the News Reporters in manifestations of behavioral and emotional disturbances. It is concluded that significant negative emotional and behavioral reactions are exhibited by the News Reporters who cover traumatic events. The study identifies the negative emotional and behavioral reactions/disturbances after trauma, which can be helpful for identifying problematic areas for counseling and therapeutic interventions for these News Reporters.

Keywords: behavioural disturbance, emotional disturbance, news reporters, traumatic events

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5052 Effective Leadership in the Engineering, Technology, and Construction Industry

Authors: David W. Farler, Perry Haan

Abstract:

This paper explores what effective leadership is being employed in the engineering, technology, and construction (ETC) industry. Organizations need to understand what character traits are being used and what leadership styles work to promote sustainability and improve the triple bottom line. This paper looks at multiple publications on leadership and character traits effective for managers and leaders in the ETC industry. The ETC industry is a trillion-dollar industry, and understanding ways to improve leadership is vital for organizations' successful outcomes. With improvements to the managerial and leadership, there could be ways for organizations to profit more and cut down on cost costs. Finding ways to improve motivation can help organizations improve safety, improve culture, and increase employee motivation. From the research, this paper has found that situational leadership, transformational, and transactional are the most effective leadership styles that individuals can use in the ETC industry for leadership. Character traits that are the most effective have been identified in this research paper. This research has contributed to the ways individuals who start in the engineering and technology industry can improve upon their leadership skills as they are promoted into managerial and leadership roles. The need for managerial positions in the ETC industry, such as project and construction managers, to improve is vital for successful outcomes and creating a high-level performance. The study helps provide a gap in the limited research available to improve ETC leadership for all organizations' present and future.

Keywords: construction, effective leadership, engineering, technology

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5051 The Influence of Water and Salt Crystals Content on Thermal Conductivity Coefficient of Red Clay Brick

Authors: Dalia Bednarska, Marcin Koniorczyk

Abstract:

This paper presents results of experiments aimed at studying hygro-thermal properties of red clay brick. The main objective of research was to investigate the relation between thermal conductivity coefficient of brick and its water or Na2SO4 solution content. The research was conducted using stationary technique for the totally dried specimens, as well as the ones 25%, 50%, 75% and 100% imbued with water or sodium sulfate solution. Additionally, a sorption isotherm test was conducted for seven relative humidity levels. Furthermore the change of red clay brick pore structure before and after imbuing with water and salt solution was investigated by multi-cycle mercury intrusion test. The experimental results confirm negative influence of water or sodium sulphate on thermal properties of material. The value of thermal conductivity coefficient increases along with growth of water or Na₂SO₄ solution content. The study shows that the presence of Na₂SO₄ solution has less negative influence on brick’s thermal conductivity coefficient than water.

Keywords: building materials, red clay brick, sodium sulfate, thermal conductivity coefficient

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5050 Study of Silent Myocardial Ischemia in Type 2 Diabeic Males: Egyptian Experience

Authors: Ali Kassem, Yhea Kishik, Ali Hassan, Mohamed Abdelwahab

Abstract:

Introduction: Accelerated coronary and peripheral vascular atherosclerosis is one of the most common and chronic complications of diabetes mellitus. A recent aspect of coronary artery disease in this condition is its silent nature. The aim of the work: Detection of the prevalence of silent myocardial ischemia (SMI) in Upper Egypt type 2 diabetic males and to select male diabetic population who should be screened for SMI. Patients and methods: 100 type 2 diabetic male patients with a negative history of angina or anginal equivalent symptoms and 30 healthy control were included. Full medical history and thorough clinical examination were done for all participants. Fasting and post prandial blood glucose level, lipid profile, (HbA1c), microalbuminuria, and C-reactive protein were done for all participants Resting ECG, trans-thoracic echocardiography, treadmill exercise ECG, myocardial perfusion imaging were done for all participants and patients positive for one or more NITs were subjected for coronary angiography. Results Twenty nine patients (29%) were positive for one or more NITs in the patients group compared to only one case (3.3%) in the controls. After coronary angiography, 20 patients were positive for significant coronary artery stenosis in the patients group, while it was refused to be done by the patient in the controls. There were statistical significant difference between the two groups regarding, hypertension, dyslipidemia and obesity, family history of DM and IHD with higher levels of microalbuminuria, C-reactive protein, total lipids in patient group versus controls According to coronary angiography, patients were subdivided into two subgroups, 20 positive for SMI (positive for coronary angiography) and 80 negative for SMI (negative for coronary angiography). No statistical difference regarding family history of DM and type of diabetic therapy was found between the two subgroups. Yet, smoking, hypertension, obesity, dyslipidemia and family history of IHD were significantly higher in diabetics positive versus those negative for SMI. 90% of patients in subgroup positive for SMI had two or more cardiac risk factors while only two patients had one cardiac risk factor (10%). Uncontrolled DM was detected more in patients positive for SMI. Diabetic complications were more prevalent in patients positive for SMI versus those negative for SMI. Most of the patients positive for SMI have DM more than 5 years duration. Resting ECG and resting Echo detected only 6 and 11 cases, respectively, of the 20 positive cases in group positive for SMI compared to treadmill exercise ECG and myocardial perfusion imaging that detected 16 and 18 cases respectively, Conclusion: Type 2 diabetic male patients should be screened for detection of SMI when aged above 50 years old, diabetes duration is more than 5 years, presence of two or more cardiac risk factors and/or patients suffering from one or more of the chronic diabetic complications. CRP, is an important parameter for selection of type 2 diabetic male patients who should be screened for SMI. Non invasive cardiac tests are reliable for screening of SMI in these patients in our locality.

Keywords: C-reactive protein, Silent myocardial ischemia, Stress tests, type 2 DM

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5049 Efficient of Technology Remediation Soil That Contaminated by Petroleum Based on Heat without Combustion

Authors: Gavin Hutama Farandiarta, Hegi Adi Prabowo, Istiara Rizqillah Hanifah, Millati Hanifah Saprudin, Raden Iqrafia Ashna

Abstract:

The increase of the petroleum’s consumption rate encourages industries to optimize and increase the activity in processing crude oil into petroleum. However, although the result gives a lot of benefits to humans worldwide, it also gives negative impact to the environment. One of the negative impacts of processing crude oil is the soil will be contaminated by petroleum sewage sludge. This petroleum sewage sludge, contains hydrocarbon compound and it can be calculated by Total Petroleum Hydrocarbon (TPH).Petroleum sludge waste is accounted as hazardous and toxic. The soil contamination caused by the petroleum sludge is very hard to get rid of. However, there is a way to manage the soil that is contaminated by petroleum sludge, which is by using heat (thermal desorption) in the process of remediation. There are several factors that affect the success rate of the remediation with the help of heat which are temperature, time, and air pressure in the desorption column. The remediation process using the help of heat is an alternative in soil recovery from the petroleum pollution which highly effective, cheap, and environmentally friendly that produces uncontaminated soil and the petroleum that can be used again.

Keywords: petroleum sewage sludge, remediation soil, thermal desorption, total petroleum hydrocarbon (TPH)

Procedia PDF Downloads 247
5048 Laparoscopic Curative Resection for Right-Sided Colonic Tumours: Initial Experience from a Cancer Hospital of a Developing Country

Authors: Awais Naeem, Osama Shakeel, Aamir Ali Syed, Shahid Khattak

Abstract:

Introduction: Laparoscopic right hemicolectomy is an advanced cancer surgery in today's era. The aim of this study was to evaluate the surgical and initial oncological outcomes after curative, laparoscopic resection of right sided colonic tumors. Also to compare our results with those of previous randomized trials. Methods And Procedures: We retrospectively analyzed the medical record files of all the patients who presented to our hospital with the diagnosis of right sided colon carcinoma from January 2012 to December 2017 and underwent laparoscopic right hemicolectomy. Demographics, operative findings and histopathological reports were all recorded on a preformed data sheet. All the analysis was performed on SPSS 20. Results: Total of 48 patients were included. There were 37 male and 11 female patients with mean age of 49.7 (range from 25 – 82). Mean hospital stay was 8.25 ± 3.17 days. Blood loss was 80mls and operative mean time was 240 minutes. Eighteen patients had extended right hemicolectomy. Median length of the specimen retrieved was 31cm (range, 14-59cm). Mean size of tumor was 6.44cm + 2.53. Total number of lymph nodes removed was 20.5 + 8.3. All had R0 resection. Post-operatively 2 patients had pelvic collection and there was no 30 day mortality. In 33 patients there was T3 disease, 5 had T2 and 10 had T4 disease. There was distant recurrence in 4 patients with peritoneal metastasis in 3 and liver metastasis in 1 patient. Forty-six patients are still alive and 44 are disease free. The mean follow-up period was 25.31 (12 to 60) months. Conclusion: Our early experience with Laparascopic Right hemicolectomy as a safe and oncologically feasible surgical option. We attained comparable surgical results with curative intent.

Keywords: right hemicolectomy, right sided colonic tumors, laparoscopic, curative intent

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5047 Flexible Feedstock Concept in Gasification Process for Carbon-Negative Energy Technology: A Case Study in Malaysia

Authors: Zahrul Faizi M. S., Ali A., Norhuda A. M.

Abstract:

Emission of greenhouse gases (GHG) from solid waste treatment and dependency on fossil fuel to produce electricity are the major concern in Malaysia as well as global. Innovation in downdraft gasification with combined heat and power (CHP) systems has the potential to minimize solid waste and reduce the emission of anthropogenic GHG from conventional fossil fuel power plants. However, the efficiency and capability of downdraft gasification to generate electricity from various alternative fuels, for instance, agriculture residues (i.e., woodchip, coconut shell) and municipal solid waste (MSW), are still controversial, on top of the toxicity level from the produced bottom ash. Thus this study evaluates the adaptability and reliability of the 20 kW downdraft gasification system to generate electricity (while considering environmental sustainability from the bottom ash) using flexible local feedstock at 20, 40, and 60% mixed ratio of MSW: agriculture residues. Feedstock properties such as feed particle size, moisture, and ash contents are also analyzed to identify optimal characteristics for the combination of feedstock (feedstock flexibility) to obtain maximum energy generation. Results show that the gasification system is capable to flexibly accommodate different feedstock compositions subjected to specific particle size (less than 2 inches) at a moisture content between 15 to 20%. These values exhibit enhance gasifier performance and provide a significant effect to the syngas composition utilizes by the internal combustion engine, which reflects energy production. The result obtained in this study is able to provide a new perspective on the transition of the conventional gasification system to a future reliable carbon-negative energy technology. Subsequently, promoting commercial scale-up of the downdraft gasification system.

Keywords: carbon-negative energy, feedstock flexibility, gasification, renewable energy

Procedia PDF Downloads 135
5046 Unpowered Knee Exoskeleton with Compliant Joints for Stair Descent Assistance

Authors: Pengfan Wu, Xiaoan Chen, Ye He, Tianchi Chen

Abstract:

This paper introduces the design of an unpowered knee exoskeleton to assist human walking by redistributing the moment of the knee joint during stair descent (SD). Considering the knee moment varying with the knee joint angle and the work of the knee joint is all negative, the custom-built spring was used to convert negative work into the potential energy of the spring during flexion, and the obtained energy work as assistance during extension to reduce the consumption of lower limb muscles. The human-machine adaptability problem was left by traditional rigid wearable due to the knee involves sliding and rotating without a fixed-axis rotation, and this paper designed the two-direction grooves to follow the human-knee kinematics, and the wire spring provides a certain resistance to the pin in the groove to prevent extra degrees of freedom. The experiment was performed on a normal stair by healthy young wearing the device on both legs with the surface electromyography recorded. The results show that the quadriceps (knee extensor) were reduced significantly.

Keywords: unpowered exoskeleton, stair descent, knee compliant joint, energy redistribution

Procedia PDF Downloads 125
5045 Structural Characterization of TIR Domains Interaction

Authors: Sara Przetocka, Krzysztof Żak, Grzegorz Dubin, Tadeusz Holak

Abstract:

Toll-like receptors (TLRs) play central role in the innate immune response and inflammation by recognizing pathogen-associated molecular patterns (PAMPs). A fundamental basis of TLR signalling is dependent upon the recruitment and association of adaptor molecules that contain the structurally conserved Toll/interleukin-1 receptor (TIR) domain. MyD88 (myeloid differentiation primary response gene 88) is the universal adaptor for TLRs and cooperates with Mal (MyD88 adapter-like protein, also known as TIRAP) in TLR4 response which is predominantly used in inflammation, host defence and carcinogenesis. Up to date two possible models of MyD88, Mal and TLR4 interactions have been proposed. The aim of our studies is to confirm or abolish presented models and accomplish the full structural characterisation of TIR domains interaction. Using molecular cloning methods we obtained several construct of MyD88 and Mal TIR domain with GST or 6xHis tag. Gel filtration method as well as pull-down analysis confirmed that recombinant TIR domains from MyD88 and Mal are binding in complexes. To examine whether obtained complexes are homo- or heterodimers we carried out cross-linking reaction of TIR domains with BS3 compound combined with mass spectrometry. To investigate which amino acid residues are involved in this interaction the NMR titration experiments were performed. 15N MyD88-TIR solution was complemented with non-labelled Mal-TIR. The results undoubtedly indicate that MyD88-TIR interact with Mal-TIR. Moreover 2D spectra demonstrated that simultaneously Mal-TIR self-dimerization occurs which is necessary to create proper scaffold for Mal-TIR and MyD88-TIR interaction. Final step of this study will be crystallization of MyD88 and Mal TIR domains complex. This crystal structure and characterisation of its interface will have an impact in understanding the TLR signalling pathway and possibly will be used in development of new anti-cancer treatment.

Keywords: cancer, MyD88, TIR domains, Toll-like receptors

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