Search results for: double injection
Commenced in January 2007
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Edition: International
Paper Count: 2073

Search results for: double injection

243 Comparative Analysis of Costs and Well Drilling Techniques for Water, Geothermal Energy, Oil and Gas Production

Authors: Thales Maluf, Nazem Nascimento

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The development of society relies heavily on the total amount of energy obtained and its consumption. Over the years, there has been an advancement on energy attainment, which is directly related to some natural resources and developing systems. Some of these resources should be highlighted for its remarkable presence in world´s energy grid, such as water, petroleum, and gas, while others deserve attention for representing an alternative to diversify the energy grid, like geothermal sources. Therefore, because all these resources can be extracted from the underground, drilling wells is a mandatory activity in terms of exploration, and it involves a previous geological study and an adequate preparation. It also involves a cleaning process and an extraction process that can be executed by different procedures. For that reason, this research aims the enhancement of exploration processes through a comparative analysis of drilling costs and techniques used to produce them. The analysis itself is based on a bibliographical review based on books, scientific papers, schoolwork and mainly explore drilling methods and technologies, equipment used, well measurements, extraction methods, and production costs. Besides techniques and costs regarding the drilling processes, some properties and general characteristics of these sources are also compared. Preliminary studies show that there are some major differences regarding the exploration processes, mostly because these resources are naturally distinct. Water wells, for instance, have hundreds of meters of length because water is stored close to the surface, while oil, gas, and geothermal production wells can reach thousands of meters, which make them more expensive to be drilled. The drilling methods present some general similarities especially regarding the main mechanism of perforation, but since water is a resource stored closer to the surface than the other ones, there is a wider variety of methods. Water wells can be drilled by rotary mechanisms, percussion mechanisms, rotary-percussion mechanisms, and some other simpler methods. Oil and gas production wells, on the other hand, require rotary or rotary-percussion drilling with a proper structure called drill rig and resistant materials for the drill bits and the other components, mostly because they´re stored in sedimentary basins that can be located thousands of meters under the ground. Geothermal production wells also require rotary or rotary-percussion drilling and require the existence of an injection well and an extraction well. The exploration efficiency also depends on the permeability of the soil, and that is why it has been developed the Enhanced Geothermal Systems (EGS). Throughout this review study, it can be verified that the analysis of the extraction processes of energy resources is essential since these resources are responsible for society development. Furthermore, the comparative analysis of costs and well drilling techniques for water, geothermal energy, oil, and gas production, which is the main goal of this research, can enable the growth of energy generation field through the emergence of ideas that improve the efficiency of energy generation processes.

Keywords: drilling, water, oil, Gas, geothermal energy

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242 Characterization of β-Lactamases Resistance amongst Acinetobacter Baumannii Isolated from Clinical Samples, Egypt

Authors: Amal Saafan, Kareem Al Sofy, Sameh AbdelGhani, Magdy Amin

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Background: Acinetobacter spp. resistance towards β-lactam antibiotics is mediated mainly by different classes of β-lactamases production; detection of some genes responsible for production of β-lactamases is the objective of the study. Methods: One hundred fifty bacterial isolates were recovered from blood, sputum, and urine specimens from different hospitals in Egypt. Sixty-nine isolate were identified as Acinetobacter baumannii using traditional biochemical tests, CHROM agar, MicroScan and PCR amplification of blaoxa-51like gene. Acinetobacterbaumannii isolates were grouped into carbapenem resistant group (GP1), cefotaxime, ceftazidime and cefoxitin resistant group (GP2) and carbapenem and cephalosporin non-resistant group (GP3). Carbapenemase activity was screened using modified Hodge test (MHT) for GP1.Metallo-β-lactamases screening was performed for MHT positive isolates using double disk synergy test (DDST) and combined disk test (CDT). Amp C activity was screened using Amp C disk test with Tris-EDTA, DDST, and CDT for GP2. Finally, PCR amplification of blaoxa-51like, blaoxa-23like, blaIMP-like, blaVIM-like, and blaADC-like genes was performed for isolates that showed, at least, two positive results of three for both AmpC and carbapenemases phenotypic screening tests (obvious activity), in addition to GP3 (for comparison). Detection of blaoxa-51like and blaADC-like genes preceded by ISAba1 was also performed. Results: Antibiogram of 69 pure Acinetobacter baumannii isolates resulted in 57, 64, and 2 isolates enrolled into GP1, GP2, and GP3, respectively. Carbapenemase activity was shown by 49(85.9%) isolate using MHT. Metallo-β-lactamases screening revealed 32(65.3%) and 35(71.4%) using DDST and CDT, respectively.AmpC activity was shown by 43(67.2%) and 50 (78.1%) isolates using AmpC disk test with Tris-EDTA, and both DDST and CDT, respectively. Twenty-seven isolates showed obvious activity, all of them (100%) were harboring blaoxa-51like and blaADC-like genes, while blaoxa-23like, blaIMP-like andblaVIM-like genes were harbored by 23(85.2%), 9 (33.%) and no isolate respectively. Only 12 (44.4%) isolates harbored blaoxa-51like and blaADC-like genes preceded by ISAba1. GP3 isolates showed only positive blaoxa-51like and blaADC-like genes. Conclusion: It is not possible to correlate resistance with presence of blaoxa-51like and blaADC-like genes and presence of ISAba1 was immediate as transcriptional promoter. A blaoxa-23like gene played an important role in carbapenem resistance when compared with blaIMP-like and blaVIM-like gene.

Keywords: acinetobacter, beta-lactams, resistance, antimicrobial agents

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241 Study on Co-Relation of Prostate Specific Antigen with Metastatic Bone Disease in Prostate Cancer on Skeletal Scintigraphy

Authors: Muhammad Waleed Asfandyar, Akhtar Ahmed, Syed Adib-ul-Hasan Rizvi

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Objective: To evaluate the ability of serum concentration of prostate specific antigen between two cutting points considering it as a predictor of skeletal metastasis on bone scintigraphy in men with prostate cancer. Settings: This study was carried out in department of Nuclear Medicine at Sindh Institute of Urology and Transplantation (SIUT) Karachi, Pakistan. Materials and Method: From August 2013 to November 2013, forty two (42) consecutive patients with prostate cancer who underwent technetium-99m methylene diphosphonate (Tc-99mMDP) whole body bone scintigraphy were prospectively analyzed. The information was collected from the scintigraphic database at a Nuclear medicine department Sindh institute of urology and transplantation Karachi Pakistan. Patients who did not have a serum PSA concentration available within 1 month before or after the time of performing the Tc-99m MDP whole body bone scintigraphy were excluded from this study. A whole body bone scintigraphy scan (from the toes to top of the head) was performed using a whole-body Moving gamma camera technique (anterior and posterior) 2–4 hours after intravenous injection of 20 mCi of Tc-99m MDP. In addition, all patients necessarily have a pathological report available. Bony metastases were determined from the bone scan studies and no further correlation with histopathology or other imaging modalities were performed. To preserve patient confidentiality, direct patient identifiers were not collected. In all the patients, Prostate specific antigen values and skeletal scintigraphy were evaluated. Results: The mean age, mean PSA, and incidence of bone metastasis on bone scintigraphy were 68.35 years, 370.51 ng/mL and 19/42 (45.23%) respectively. According to PSA levels, patients were divided into 5 groups < 10ng/mL (10/42), 10-20 ng/mL (5/42), 20-50 ng/mL (2/42), 50-100 (3/42), 100- 500ng/mL (3/42) and more than 500ng/mL (0/42) presenting negative bone scan. The incidence of positive bone scan (%) for bone metastasis for each group were O1 patient (5.26%), 0%, 03 patients (15.78%), 01 patient (5.26%), 04 patients (21.05%), and 10 patients (52.63%) respectively. From the 42 patients 19 (45.23%) presented positive scintigraphic examination for the presence of bone metastasis. 1 patient presented bone metastasis on bone scintigraphy having PSA level less than 10ng/mL, and in only 1 patient (5.26%) with bone metastasis PSA concentration was less than 20 ng/mL. therefore, when the cutting point adopted for PSA serum concentration was 10ng/mL, a negative predictive value for bone metastasis was 95% with sensitivity rates 94.74% and the positive predictive value and specificities of the method were 56.53% and 43.48% respectively. When the cutting point of PSA serum concentration was 20ng/mL the observed results for Positive predictive value and specificity were (78.27% and 65.22% respectively) whereas negative predictive value and sensitivity stood (100% and 95%) respectively. Conclusion: Results of our study allow us to conclude that serum PSA concentration of higher than 20ng/mL was the most accurate cutting point than a serum concentration of PSA higher than 10ng/mL to predict metastasis in radionuclide bone scintigraphy. In this way, unnecessary cost can be avoided, since a considerable part of prostate adenocarcinomas present low serum PSA levels less than 20 ng/mL and for these cases radionuclide bone scintigraphy could be unnecessary.

Keywords: bone scan, cut off value, prostate specific antigen value, scintigraphy

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240 Getting to Know ICU Nurses and Their Duties

Authors: Masih Nikgou

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ICU nurses or intensive care nurses are highly specialized and trained healthcare personnel. These nurses provide nursing care for patients with life-threatening illnesses or conditions. They provide the experience, knowledge and specialized skills that patients need to survive and recover. Intensive care nurses (ICU) are trained to make momentary decisions and act quickly when the patient's condition changes. Their primary work environment is in the hospital in intensive care units. Typically, ICU patients require a high level of care. ICU nurses work in challenging and complex fields in their nursing profession. They have the primary duty of caring for and saving patients who are fighting for their lives. Intensive care (ICU) nurses are highly trained to provide exceptional care to patients who depend on 24/7 nursing care. A patient in the ICU is often equipped with a ventilator, intubated and connected to several life support machines and medical equipment. Intensive Care Nurses (ICU) have full expertise in considering all aspects of bringing back their patients. Some of the specific responsibilities of ICU nurses include (a) Assessing and monitoring the patient's progress and identifying any sudden changes in the patient's medical condition. (b) Administration of drugs intravenously by injection or through gastric tubes. (c) Provide regular updates on patient progress to physicians, patients, and their families. (d) According to the clinical condition of the patient, perform the approved diagnostic or treatment methods. (e) In case of a health emergency, informing the relevant doctors. (f) To determine the need for emergency interventions, evaluate laboratory data and vital signs of patients. (g) Caring for patient needs during recovery in the ICU. (h) ICU nurses often provide emotional support to patients and their families. (i) Regulating and monitoring medical equipment and devices such as medical ventilators, oxygen delivery devices, transducers, and pressure lines. (j) Assessment of pain level and sedation needs of patients. (k) Maintaining patient reports and records. As the name suggests, critical care nurses work primarily in ICU health care units. ICUs are completely healthy and have proper lighting with strict adherence to health and safety from medical centers. ICU nurses usually move between the intensive care unit, the emergency department, the operating room, and other special departments of the hospital. ICU nurses usually follow a standard shift schedule that includes morning, afternoon, and night schedules. There are also other relocation programs depending on the hospital and region. Nurses who are passionate about data and managing a patient's condition and outcomes typically do well as ICU nurses. An inquisitive mind and attention to processes are equally important. ICU nurses are completely compassionate and are not afraid to advocate for their patients and family members. who are distressed.

Keywords: nursing, intensive care unit, pediatric intensive care unit, mobile intensive care unit, surgical intensive care unite

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239 Internal Mercury Exposure Levels Correlated to DNA Methylation of Imprinting Gene H19 in Human Sperm of Reproductive-Aged Man

Authors: Zhaoxu Lu, Yufeng Ma, Linying Gao, Li Wang, Mei Qiang

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Mercury (Hg) is a well-recognized environmental pollutant known by its toxicity of development and neurotoxicity, which may result in adverse health outcomes. However, the mechanisms underlying the teratogenic effects of Hg are not well understood. Imprinting genes are emerging regulators for fetal development subject to environmental pollutants impacts. In this study, we examined the association between paternal preconception Hg exposures and the alteration of DNA methylation of imprinting genes in human sperm DNA. A total of 618 men aged from 22 to 59 was recruited from the Reproductive Medicine Clinic of Maternal and Child Care Service Center and the Urologic Surgery Clinic of Shanxi Academy of Medical Sciences during April 2015 and March 2016. Demographic information was collected using questionnaires. Urinary Hg concentrations were measured using a fully-automatic double-channel hydride generation atomic fluorescence spectrometer. And methylation status in the DMRs of imprinting genes H19, Meg3 and Peg3 of sperm DNA were examined by bisulfite pyrosequencing in 243 participants. Spearman’s rank and multivariate regression analysis were used for correlation analysis between sperm DNA methylation status of imprinting genes and urinary Hg levels. The median concentration of Hg for participants overall was 9.09μg/l (IQR: 5.54 - 12.52μg/l; range = 0 - 71.35μg/l); no significant difference was found in median concentrations of Hg among various demographic groups (p > 0.05). The proportion of samples that a beyond intoxication criterion (10μg/l) for urinary Hg was 42.6%. Spearman’s rank correlation analysis indicates a negative correlation between urinary Hg concentrations and average DNA methylation levels in the DMRs of imprinted genes H19 (rs=﹣0.330, p = 0.000). However, there was no such a correlation found in genes of Peg3 and Meg3. Further, we analyzed of correlation between methylation level at each CpG site of H19 and Hg level, the results showed that three out of 7 CpG sites on H19 DMR, namely CpG2 (rs =﹣0.138, p = 0.031), CpG4 (rs =﹣0.369, p = 0.000) and CpG6 (rs=﹣0.228, p = 0.000), demonstrated a significant negative correlation between methylation levels and the levels of urinary Hg. After adjusting age, smoking, drinking, intake of aquatic products and education by multivariate regression analysis, the results have shown a similar correlation. In summary, mercury nonoccupational environmental exposure in reproductive-aged men associated with altered DNA methylation outcomes at DMR of imprinting gene H19 in sperm, implicating the susceptibility of the developing sperm for environmental insults.

Keywords: epigenetics, genomic imprinting gene, DNA methylation, mercury, transgenerational effects, sperm

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238 The Relationship Between Exposure to Traumatic Events in the Delivery Room, Post-Traumatic Stress Symptoms, Personal Resilience, Organizational Commitment, and Professional Quality of Life Among Midwives

Authors: Kinneret Segal

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Background: The work of a midwife is emotionally challenging, both positively and negatively. Midwives share moments of joy when a baby is welcomed into the world and also attend difficult events of loss and trauma. The relationship that develops with the maternity is the essence of the midwife's care, and it is a fundamental source of motivation and professional satisfaction. This close relationship with the maternity may be used as a double-edged sword in cases of exposure to traumatic events at birth. Birth problems, exposure to emergencies and traumatic events, and loss can affect the professional quality of life and the Compassion satisfaction of the midwife. It seems that the issue of traumatic experiences in the work of midwives has not been sufficiently explored. Aim: The present study examined the associations between exposure to traumatic events, personal resilience and post-traumatic symptoms, professional quality of life, and organizational commitment among midwifery nurses in Israeli hospitals. Methods: 131 midwives from three hospitals in the country's center in Israel participated in this study. The data were collected during 2021 using a self-report questionnaire that examined sociodemographic characteristics, the degree of exposure to traumatic events in the delivery room, personal resilience, post-traumatic symptoms, professional quality of life, and organizational commitment. Results: The three most difficult traumatic events for the midwives were death or fear of death of a newborn, death or fear of the death of a mother, and a quiet birth. The higher the frequency of exposure to traumatic events, the more numerous and intense the onset of post-trauma symptoms. The more numerous and powerful the post-trauma symptoms, the higher the level of professional burnout and/or compassion fatigue, and the lower the level of compassion satisfaction. High levels of compassion satisfaction and/or low professional burnout were expressed in a heightened sense of organizational commitment. Personal resilience, country of birth, traumatic symptoms, and organizational commitment predicted satisfaction from compassion. Conclusions: Midwives are exposed to traumatic events associated with dissatisfaction and impairment of the professional quality of life that accompanies burnout and compassion fatigue. Exposure to traumatic events leads to the appearance of traumatic symptoms, a decrease in organizational commitment, and psychological and mental well-being. The issue needs to be addressed by implementing training programs, organizational support, and policies to improving well-being and quality of care among midwives.

Keywords: organizational commitment, traumatic experiences, personal resilience, quality of life

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237 Stilbenes as Sustainable Antimicrobial Compounds to Control Vitis Vinifera Diseases

Authors: David Taillis, Oussama Becissa, Julien Gabaston, Jean-Michel Merillon, Tristan Richard, Stephanie Cluzet

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Nowadays, there is a strong pressure to reduce the phytosanitary inputs of synthetic chemistry in vineyards. It is, therefore, necessary to find viable alternatives in order to protect the vine against its major diseases. For this purpose, we suggest the use of a plant extract enriched in antimicrobial compounds. Being produced from vine trunks and roots, which are co-products of wine production, the extract produced is part of a circular economy. The antimicrobial molecules present in this plant material are polyphenols and, more particularly, stilbenes, which are derived from a common base, the resveratrol unit, and that are well known vine phytoalexins. The stilbenoids were extracted from trunks and roots (30/70, w/w) by a double extraction with ethyl acetate followed by enrichment by liquid-liquid extraction. The produced extract was characterized by UHPLC-MS, then its antimicrobial activities were tested on Plasmopara viticola and Botrytis cinerea in the laboratory and/or in greenhouse and in vineyard. The major compounds were purified, and their antimicrobial activity was evaluated on B. cinerea. Moreover, after its spraying, the effect of the stilbene extract on the plant defence status was evaluated by analysis of defence gene expression. UHPLC-MS analysis revealed that the extract contains 50% stilbenes with resveratrol, ε-viniferin and r-viniferin as major compounds. The extract showed antimicrobial activities on P. viticola with IC₅₀ and IC₁₀₀ respectively of 90 and 300 mg/L in the laboratory. In addition, it inhibited 40% of downy mildew development in greenhouse. However, probably because of the sensitivity of stilbenes to the environment, such as UV degradation, no activity has been observed in vineyard towards P. viticola development. For B. cinerea, the extract IC50 was 123 mg/L, with resveratrol and ε-viniferin being the most active stilbenes (IC₅₀ of 88 and 142 mg/L, respectively). The analysis of the expression of defence genes revealed that the extract can induce the expression of some defence genes 24, 48, and 72 hours after treatment, meaning that the extract has a defence-stimulating effect at least for the first three days after treatment. In conclusion, we produced a plant extract enriched in stilbenes with antimicrobial properties against two major grapevine pathogenic agents P. viticola and B. cinerea. In addition, we showed that this extract displayed eliciting activity of plant defences. This extract can therefore represent, after formulation development, a viable eco-friendly alternative for vineyard protection. Subsequently, the effect of the stilbenoid extract on primary metabolism will be evaluated by quantitative NMR.

Keywords: antimicrobial, bioprotection, grapevine, Plasmopara viticola, stilbene

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236 Characterization of a Lipolytic Enzyme of Pseudomonas nitroreducens Isolated from Mealworm's Gut

Authors: Jung-En Kuan, Whei-Fen Wu

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In this study, a symbiotic bacteria from yellow mealworm's (Tenebrio molitor) mid-gut was isolated with characteristics of growth on minimal-tributyrin medium. After a PCR-amplification of its 16s rDNA, the resultant nucleotide sequences were then analyzed by schemes of the phylogeny trees. Accordingly, it was designated as Pseudomonas nitroreducens D-01. Next, by searching the lipolytic enzymes in its protein data bank, one of those potential lipolytic α/β hydrolases was identified, again using PCR-amplification and nucleotide-sequencing methods. To construct an expression of this lipolytic gene in plasmids, the target-gene primers were then designed, carrying the C-terminal his-tag sequences. Using the vector pET21a, a recombinant lipolytic hydrolase D gene with his-tag nucleotides was successfully cloned into it, of which the lipolytic D gene is under a control of the T7 promoter. After transformation of the resultant plasmids into Eescherichia coli BL21 (DE3), an IPTG inducer was used for the induction of the recombinant proteins. The protein products were then purified by metal-ion affinity column, and the purified proteins were found capable of forming a clear zone on tributyrin agar plate. Shortly, its enzyme activities were determined by degradation of p-nitrophenyl ester(s), and the substantial yellow end-product, p-nitrophenol, was measured at O.D.405 nm. Specifically, this lipolytic enzyme efficiently targets p-nitrophenyl butyrate. As well, it shows the most reactive activities at 40°C, pH 8 in potassium phosphate buffer. In thermal stability assays, the activities of this enzyme dramatically drop when the temperature is above 50°C. In metal ion assays, MgCl₂ and NH₄Cl induce the enzyme activities while MnSO₄, NiSO₄, CaCl₂, ZnSO₄, CoCl₂, CuSO₄, FeSO₄, and FeCl₃ reduce its activities. Besides, NaCl has no effects on its enzyme activities. Most organic solvents decrease the activities of this enzyme, such as hexane, methanol, ethanol, acetone, isopropanol, chloroform, and ethyl acetate. However, its enzyme activities increase when DMSO exists. All the surfactants like Triton X-100, Tween 80, Tween 20, and Brij35 decrease its lipolytic activities. Using Lineweaver-Burk double reciprocal methods, the function of the enzyme kinetics were determined such as Km = 0.488 (mM), Vmax = 0.0644 (mM/min), and kcat = 3.01x10³ (s⁻¹), as well the total efficiency of kcat/Km is 6.17 x10³ (mM⁻¹/s⁻¹). Afterwards, based on the phylogenetic analyses, this lipolytic protein is classified to type IV lipase by its homologous conserved region in this lipase family.

Keywords: enzyme, esterase, lipotic hydrolase, type IV

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235 Targeted Delivery of Docetaxel Drug Using Cetuximab Conjugated Vitamin E TPGS Micelles Increases the Anti-Tumor Efficacy and Inhibit Migration of MDA-MB-231 Triple Negative Breast Cancer

Authors: V. K. Rajaletchumy, S. L. Chia, M. I. Setyawati, M. S. Muthu, S. S. Feng, D. T. Leong

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Triple negative breast cancers (TNBC) can be classified as one of the most aggressive with a high rate of local recurrences and systematic metastases. TNBCs are insensitive to existing hormonal therapy or targeted therapies such as the use of monoclonal antibodies, due to the lack of oestrogen receptor (ER) and progesterone receptor (PR) and the absence of overexpression of human epidermal growth factor receptor 2 (HER2) compared with other types of breast cancers. The absence of targeted therapies for selective delivery of therapeutic agents into tumours, led to the search for druggable targets in TNBC. In this study, we developed a targeted micellar system of cetuximab-conjugated micelles of D-α-tocopheryl polyethylene glycol succinate (vitamin E TPGS) for targeted delivery of docetaxel as a model anticancer drug for the treatment of TNBCs. We examined the efficacy of our micellar system in xenograft models of triple negative breast cancers and explored the effect of the micelles on post-treatment tumours in order to elucidate the mechanism underlying the nanomedicine treatment in oncology. The targeting micelles were found preferentially accumulated in tumours immediately after the administration of the micelles compare to normal tissue. The fluorescence signal gradually increased up to 12 h at the tumour site and sustained for up to 24 h, reflecting the increases in targeted micelles (TPFC) micelles in MDA-MB-231/Luc cells. In comparison, for the non-targeting micelles (TPF), the fluorescence signal was evenly distributed all over the body of the mice. Only a slight increase in fluorescence at the chest area was observed after 24 h post-injection, reflecting the moderate uptake of micelles by the tumour. The successful delivery of docetaxel into tumour by the targeted micelles (TPDC) exhibited a greater degree of tumour growth inhibition than Taxotere® after 15 days of treatment. The ex vivo study has demonstrated that tumours treated with targeting micelles exhibit enhanced cell cycle arrest and attenuated proliferation compared with the control and with those treated non-targeting micelles. Furthermore, the ex vivo investigation revealed that both the targeting and non-targeting micellar formulations shows significant inhibition of cell migration with migration indices reduced by 0.098- and 0.28-fold, respectively, relative to the control. Overall, both the in vivo and ex vivo data increased the confidence that our micellar formulations effectively targeted and inhibited EGF-overexpressing MDA-MB-231 tumours.

Keywords: biodegradable polymers, cancer nanotechnology, drug targeting, molecular biomaterials, nanomedicine

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234 An Assessment of Redevelopment of Cessed Properties in the Island City of Mumbai, India

Authors: Palak Patel

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Mumbai is one of the largest cities of the country with a population of 12.44 million over 437 Sq.km, and it is known as financial hub of India. In early 20th century, with the expansion of industrialization and growth of port, a huge demand for housing was created. In response to this, government enacted rent controls. Over a period of time, due to rent controls, the existing rental housing stock has deteriorated. Therefore, in last 25 years, government has been focusing on redevelopment of these rental buildings, also called ‘Cessed buildings’, in order to provide better standard of living to the tenants and also, to supply new housing units in the market. In India, developers are the main players in the housing market as they are the supplier of maximum dwelling units in the market. Hence, government attempts are inclined toward facilitating developers for the cessed building redevelopment projects by incentivizing them through making special provisions in the development control regulations. This research focuses on the entire process of redevelopment by the developers and issues faced by the related stakeholders in the same to reduce the stress on housing. It also highlights the loopholes in the current system and inefficient functioning of the process. The research was carried out by interviewing various developers, tenants and landlords in the island city who have already gone through redevelopment. From the case studies, it is very evident that redevelopment is undoubtedly a huge profit making business. In some cases, developers make profit of almost double the amount of the investment. But yet, satisfactory results are not seen on ground. It clearly indicates that there are some issues faced by developers which have not been addressed. Some of these issues include cumbersome legal procedures, negotiations with landlords and tenants, congestion and narrow roads, small size of the plots, informal practicing of ‘Pagdi system’ and financial viability of the project. This research recommends the up gradation of the existing cessed buildings by sharing the repairing and maintenance cost between landlords and tenants and also, income levels of tenants can be traced and housing vouchers or incentives can be provided to those who actual need it so that landlord does not have to subsidize the tenants. For redevelopment, the current interventions are generalized in nature as it does not take on ground issues into the consideration. There is need to identify local issues and give area specific solutions. And also, government should play a role of mediator to ensure all the stakeholders are satisfied and project gets completed on time.

Keywords: cessed buildings, developers, government’s interventions, redevelopment, rent controls, tenants

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233 Study of the Kinetics of Formation of Carboxylic Acids Using Ion Chromatography during Oxidation Induced by Rancimat of the Oleic Acid, Linoleic Acid, Linolenic Acid, and Biodiesel

Authors: Patrícia T. Souza, Marina Ansolin, Eduardo A. C. Batista, Antonio J. A. Meirelles, Matthieu Tubino

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Lipid oxidation is a major cause of the deterioration of the quality of the biodiesel, because the waste generated damages the engines. Among the main undesirable effects are the increase of viscosity and acidity, leading to the formation of insoluble gums and sediments which cause the blockage of fuel filters. The auto-oxidation is defined as the spontaneous reaction of atmospheric oxygen with lipids. Unsaturated fatty acids are usually the components affected by such reactions. They are present as free fatty acids, fatty esters and glycerides. To determine the oxidative stability of biodiesels, through the induction period, IP, the Rancimat method is used, which allows continuous monitoring of the induced oxidation process of the samples. During the oxidation of the lipids, volatile organic acids are produced as byproducts, in addition, other byproducts, including alcohols and carbonyl compounds, may be further oxidized to carboxylic acids. By the methodology developed in this work using ion chromatography, IC, analyzing the water contained in the conductimetric vessel, were quantified organic anions of carboxylic acids in samples subjected to oxidation induced by Rancimat. The optimized chromatographic conditions were: eluent water:acetone (80:20 v/v) with 0.5 mM sulfuric acid; flow rate 0.4 mL min-1; injection volume 20 µL; eluent suppressor 20 mM LiCl; analytical curve from 1 to 400 ppm. The samples studied were methyl biodiesel from soybean oil and unsaturated fatty acids standards: oleic, linoleic and linolenic. The induced oxidation kinetics curves were constructed by analyzing the water contained in the conductimetric vessels which were removed, each one, from the Rancimat apparatus at prefixed intervals of time. About 3 g of sample were used under the conditions of 110 °C and air flow rate of 10 L h-1. The water of each conductimetric Rancimat measuring vessel, where the volatile compounds were collected, was filtered through a 0.45 µm filter and analyzed by IC. Through the kinetic data of the formation of the organic anions of carboxylic acids, the formation rates of the same were calculated. The observed order of the rates of formation of the anions was: formate >>> acetate > hexanoate > valerate for the oleic acid; formate > hexanoate > acetate > valerate for the linoleic acid; formate >>> valerate > acetate > propionate > butyrate for the linolenic acid. It is possible to suppose that propionate and butyrate are obtained mainly from linolenic acid and that hexanoate is originated from oleic and linoleic acid. For the methyl biodiesel the order of formation of anions was: formate >>> acetate > valerate > hexanoate > propionate. According to the total rate of formation these anions produced during the induced degradation of the fatty acids can be assigned the order of reactivity: linolenic acid > linoleic acid >>> oleic acid.

Keywords: anions of carboxylic acids, biodiesel, ion chromatography, oxidation

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232 From the Perspective of a Veterinarian: The Future of Plant Raw Materials Used in the Feeding of Farm Animals

Authors: Ertuğrul Yılmaz

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One of the most important occupational groups in the food chain from farm to fork is a veterinary medicine. This occupational group, which has important duties in the prevention of many zoonotic diseases and in public health, takes place in many critical control points from soil to our kitchen. It has important duties from mycotoxins transmitted from the soil to slaughterhouses or milk processing facilities. Starting from the soil, which constitutes 70% of mycotoxin contamination, up to the TMR made from raw materials obtained from the soil, there are all critical control points from feeding to slaughterhouses and milk production enterprises. We can take the precaution of mycotoxins such as Aflatoxin B1, Ochratoxin, Zearalenone, and Fumonisin, which we encounter on farms while in the field. It has been reported that aflatoxin B1 is a casenerogen and passes into milk in studies. It is likely that many mycotoxins pose significant threats to public health and will turn out to be even more dangerous over time. Even raw material storage and TMR preparation are very important for public health. The danger of fumonisin accumulating in the liver will be understood over time. Zoonotic diseases are also explained with examples. In this study, how important veterinarians are in terms of public health is explained with examples. In the two-year mycotoxin screenings, fumonisin mycotoxin was found to be very high in corn and corn by-products, and it was determined that it accumulated in the liver for a long time and remained cornic in animals. It has been determined that mycotoxins are present in all livestock feeds, poultry feeds, and raw materials, not alone, but in double-triple form. Starting from the end, mycotoxin scans should be carried out from feed to raw materials and from raw materials to soil. In this way, we prevent the transmission of mycotoxins to animals and from animals to humans. Liver protectors such as toxin binders, beta-glucan, mannan oligosaccharides, activated carbon, prebiotics, and silymarin were used in certain proportions in the total mixed ratio, and positive results were obtained. Humidity and temperature controls of raw material silos were made at certain intervals. Necropsy was performed on animals that died as a result of mycotoxicosis, and macroscopic photographs were taken of the organs. We have determined that the mycotoxin screening in experimental animals and the feeds made without detecting the presence and amount of bacterial factors affect the results of the project to be made. For this, a series of precautionary plans have been created, starting from the production processes.

Keywords: mycotoxins, feed safety, processes, public health

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231 Development of a Stable RNAi-Based Biological Control for Sheep Blowfly Using Bentonite Polymer Technology

Authors: Yunjia Yang, Peng Li, Gordon Xu, Timothy Mahony, Bing Zhang, Neena Mitter, Karishma Mody

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Sheep flystrike is one of the most economically important diseases affecting the Australian sheep and wool industry (>356M/annually). Currently, control of Lucillia cuprina relies almost exclusively on chemicals controls and the parasite has developed resistance to nearly all control chemicals used in the past. It is therefore critical to develop an alternative solution for the sustainable control and management of flystrike. RNA interference (RNAi) technologies have been successfully explored in multiple animal industries for developing parasites controls. This research project aims to develop a RNAi based biological control for sheep blowfly. Double-stranded RNA (dsRNA) has already proven successful against viruses, fungi and insects. However, the environmental instability of dsRNA is a major bottleneck for successful RNAi. Bentonite polymer (BenPol) technology can overcome this problem, as it can be tuned for the controlled release of dsRNA in the gut challenging pH environment of the blowfly larvae, prolonging its exposure time to and uptake by target cells. To investigate the potential of BenPol technology for dsRNA delivery, four different BenPol carriers were tested for their dsRNA loading capabilities, and three of them were found to be capable of affording dsRNA stability under multiple temperatures (4°C, 22°C, 40°C, 55°C) in sheep serum. Based on stability results, dsRNA from potential targeted genes was loaded onto BenPol carriers and tested in larvae feeding assays, three genes resulting in knockdowns. Meanwhile, a primary blowfly embryo cell line (BFEC) derived from L. cuprina embryos was successfully established, aim for an effective insect cell model for testing RNAi efficacy for preliminary assessments and screening. The results of this study establish that the dsRNA is stable when loaded on BenPol particles, unlike naked dsRNA rapidly degraded in sheep serum. The stable nanoparticle delivery system offered by BenPol technology can protect and increase the inherent stability of dsRNA molecules at higher temperatures in a complex biological fluid like serum, providing promise for its future use in enhancing animal protection.

Keywords: flystrike, RNA interference, bentonite polymer technology, Lucillia cuprina

Procedia PDF Downloads 61
230 Synthetic Classicism: A Machine Learning Approach to the Recognition and Design of Circular Pavilions

Authors: Federico Garrido, Mostafa El Hayani, Ahmed Shams

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The exploration of the potential of artificial intelligence (AI) in architecture is still embryonic, however, its latent capacity to change design disciplines is significant. 'Synthetic Classism' is a research project that questions the underlying aspects of classically organized architecture not just in aesthetic terms but also from a geometrical and morphological point of view, intending to generate new architectural information using historical examples as source material. The main aim of this paper is to explore the uses of artificial intelligence and machine learning algorithms in architectural design while creating a coherent narrative to be contained within a design process. The purpose is twofold: on one hand, to develop and train machine learning algorithms to produce architectural information of small pavilions and on the other, to synthesize new information from previous architectural drawings. These algorithms intend to 'interpret' graphical information from each pavilion and then generate new information from it. The procedure, once these algorithms are trained, is the following: parting from a line profile, a synthetic 'front view' of a pavilion is generated, then using it as a source material, an isometric view is created from it, and finally, a top view is produced. Thanks to GAN algorithms, it is also possible to generate Front and Isometric views without any graphical input as well. The final intention of the research is to produce isometric views out of historical information, such as the pavilions from Sebastiano Serlio, James Gibbs, or John Soane. The idea is to create and interpret new information not just in terms of historical reconstruction but also to explore AI as a novel tool in the narrative of a creative design process. This research also challenges the idea of the role of algorithmic design associated with efficiency or fitness while embracing the possibility of a creative collaboration between artificial intelligence and a human designer. Hence the double feature of this research, both analytical and creative, first by synthesizing images based on a given dataset and then by generating new architectural information from historical references. We find that the possibility of creatively understand and manipulate historic (and synthetic) information will be a key feature in future innovative design processes. Finally, the main question that we propose is whether an AI could be used not just to create an original and innovative group of simple buildings but also to explore the possibility of fostering a novel architectural sensibility grounded on the specificities on the architectural dataset, either historic, human-made or synthetic.

Keywords: architecture, central pavilions, classicism, machine learning

Procedia PDF Downloads 116
229 Building on Previous Microvalving Approaches for Highly Reliable Actuation in Centrifugal Microfluidic Platforms

Authors: Ivan Maguire, Ciprian Briciu, Alan Barrett, Dara Kervick, Jens Ducrèe, Fiona Regan

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With the ever-increasing myriad of applications of which microfluidic devices are capable, reliable fluidic actuation development has remained fundamental to the success of these microfluidic platforms. There are a number of approaches which can be taken in order to integrate liquid actuation on microfluidic platforms, which can usually be split into two primary categories; active microvalves and passive microvalves. Active microvalves are microfluidic valves which require a physical parameter change by external, or separate interaction, for actuation to occur. Passive microvalves are microfluidic valves which don’t require external interaction for actuation due to the valve’s natural physical parameters, which can be overcome through sample interaction. The purpose of this paper is to illustrate how further improvements to past microvalve solutions can largely enhance systematic reliability and performance, with both novel active and passive microvalves demonstrated. Covered within this scope will be two alternative and novel microvalve solutions for centrifugal microfluidic platforms; a revamped pneumatic-dissolvable film active microvalve (PAM) strategy and a spray-on Sol-Gel based hydrophobic passive microvalve (HPM) approach. Both the PAM and the HPM mechanisms were demonstrated on a centrifugal microfluidic platform consisting of alternating layers of 1.5 mm poly(methyl methacrylate) (PMMA) (for reagent storage) sheets and ~150 μm pressure sensitive adhesive (PSA) (for microchannel fabrication) sheets. The PAM approach differs from previous SOLUBON™ dissolvable film methods by introducing a more reliable and predictable liquid delivery mechanism to microvalve site, thus significantly reducing premature activation. This approach has also shown excellent synchronicity when performed in a multiplexed form. The HPM method utilises a new spray-on and low curing temperature (70°C) sol-gel material. The resultant double layer coating comprises a PMMA adherent sol-gel as the bottom layer and an ultra hydrophobic silica nano-particles (SNPs) film as the top layer. The optimal coating was integrated to microfluidic channels with varying cross-sectional area for assessing microvalve burst frequencies consistency. It is hoped that these microvalving solutions, which can be easily added to centrifugal microfluidic platforms, will significantly improve automation reliability.

Keywords: centrifugal microfluidics, hydrophobic microvalves, lab-on-a-disc, pneumatic microvalves

Procedia PDF Downloads 168
228 Date Palm Fruits from Oman Attenuates Cognitive and Behavioral Defects and Reduces Inflammation in a Transgenic Mice Model of Alzheimer's Disease

Authors: M. M. Essa, S. Subash, M. Akbar, S. Al-Adawi, A. Al-Asmi, G. J. Guillemein

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Transgenic (tg) mice which contain an amyloid precursor protein (APP) gene mutation, develop extracellular amyloid beta (Aβ) deposition in the brain, and severe memory and behavioral deficits with age. These mice serve as an important animal model for testing the efficacy of novel drug candidates for the treatment and management of symptoms of Alzheimer's disease (AD). Several reports have suggested that oxidative stress is the underlying cause of Aβ neurotoxicity in AD. Date palm fruits contain very high levels of antioxidants and several medicinal properties that may be useful for improving the quality of life in AD patients. In this study, we investigated the effect of dietary supplementation of Omani date palm fruits on the memory, anxiety and learning skills along with inflammation in an AD mouse model containing the double Swedish APP mutation (APPsw/Tg2576). The experimental groups of APP-transgenic mice from the age of 4 months were fed custom-mix diets (pellets) containing 2% and 4% Date palm fruits. We assessed spatial memory and learning ability, psychomotor coordination, and anxiety-related behavior in Tg and wild-type mice at the age of 4-5 months and 18-19 months using the Morris water maze test, rota rod test, elevated plus maze test, and open field test. Further, inflammatory parameters also analyzed. APPsw/Tg2576 mice that were fed a standard chow diet without dates showed significant memory deficits, increased anxiety-related behavior, and severe impairment in spatial learning ability, position discrimination learning ability and motor coordination along with increased inflammation compared to the wild type mice on the same diet, at the age of 18-19 months In contrast, PPsw/Tg2576 mice that were fed a diet containing 2% and 4% dates showed a significant improvements in memory, learning, locomotor function, and anxiety with reduced inflammatory markers compared to APPsw/Tg2576 mice fed the standard chow diet. Our results suggest that dietary supplementation with dates may slow the progression of cognitive and behavioral impairments in AD. The exact mechanism is still unclear and further extensive research needed.

Keywords: Alzheimer's disease, date palm fruits, Oman, cognitive decline, memory loss, anxiety, inflammation

Procedia PDF Downloads 402
227 Investigation of the Effects of 10-Week Nordic Hamstring Exercise Training and Subsequent Detraining on Plasma Viscosity and Oxidative Stress Levels in Healthy Young Men

Authors: H. C. Ozdamar , O. Kilic-Erkek, H. E. Akkaya, E. Kilic-Toprak, M. Bor-Kucukatay

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Nordic hamstring exercise (NHE) is used to increase hamstring muscle strength, prevent injuries. The aim of this study was to reveal the acute, long-term effects of 10-week NHE, followed by 5, 10-week detraining on anthropometric measurements, flexibility, anaerobic power, muscle architecture, damage, fatigue, oxidative stress, plasma viscosity (PV), blood lactate levels. 40 sedentary, healthy male volunteers underwent 10 weeks of progressive NHE followed by 5, 10 weeks of detraining. Muscle architecture was determined by ultrasonography, stiffness by strain elastography. Anaerobic power was assessed by double-foot standing, long jump, vertical jump, flexibility by sit-lie, hamstring flexibility tests. Creatine kinase activity, oxidant/antioxidant parameters were measured from venous blood by a commercial kit, whereas PV was determined using a cone-plate viscometer. The blood lactate level was measured from the fingertip. NHE allowed subjects to lose weight, this effect was reversed by detraining for 5 weeks. Exercise caused an increase in knee angles measured by a goniometer, which wasn’t affected by detraining. 10-week NHE caused a partially reversed increase in anaerobic performance upon detraining. NHE resulted in increment of biceps femoris long head (BFub) area, pennation angle, which was reversed by detraining of 10-weeks. Blood lactate levels, muscle pain, fatigue were increased after each exercise session. NHE didn’t change oxidant/antioxidant parameters; 5-week detraining resulted in an increase in total oxidant capacity (TOC) and oxidative stress index (OSI). Detraining of 10 weeks caused a reduction of these parameters. Acute exercise caused a reduction in PV at 1 to 10 weeks. Pre-exercise PV measured on the 10th week was lower than the basal value. Detraining caused the increment of PV. The results may guide the selection of the exercise type to increase performance and muscle strength. Knowing how much of the gains will be lost after a period of detraining can contribute to raising awareness of the continuity of the exercise. This work was supported by PAU Scientific Research Projects Coordination Unit (Project number: 2018SABE034)

Keywords: anaerobic power, detraining, Nordic hamstring exercise, oxidative stress, plasma viscosity

Procedia PDF Downloads 102
226 The Effect of Acute Consumption of a Nutritional Supplement Derived from Vegetable Extracts Rich in Nitrate on Athletic Performance

Authors: Giannis Arnaoutis, Dimitra Efthymiopoulou, Maria-Foivi Nikolopoulou, Yannis Manios

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AIM: Nitrate-containing supplements have been used extensively as ergogenic in many sports. However, extract fractions from plant-based nutritional sources high in nitrate and their effect on athletic performance, has not been systematically investigated. The purpose of the present study was to examine the possible effect of acute consumption of a “smart mixture” from beetroot and rocket on exercise capacity. MATERIAL & METHODS: 12 healthy, nonsmoking, recreationally active, males (age: 25±4 years, % fat: 15.5±5.7, Fat Free Mass: 65.8±5.6 kg, VO2 max: 45.46.1 mL . kg -1 . min -1) participated in a double-blind, placebo-controlled trial study, in a randomized and counterbalanced order. Eligibility criteria for participation in this study included normal physical examination, and absence of any metabolic, cardiovascular, or renal disease. All participants completed a time to exhaustion cycling test at 75% of their maximum power output, twice. The subjects consumed either capsules containing 360 mg of nitrate in total or placebo capsules, in the morning, under fasted state. After 3h of passive recovery the performance test followed. Blood samples were collected upon arrival of the participants and 3 hours after the consumption of the corresponding capsules. Time until exhaustion, pre- and post-test lactate concentrations, and rate of perceived exertion for the same time points were assessed. RESULTS: Paired-sample t-test analysis found a significant difference in time to exhaustion between the trial with the nitrate consumption versus placebo [16.1±3.0 Vs 13.5±2.6 min, p=0.04] respectively. No significant differences were observed for the concentrations of lactic acid as well as for the values in the Borg scale between the two trials (p>0.05). CONCLUSIONS: Based on the results of the present study, it appears that a nutritional supplement derived from vegetable extracts rich in nitrate, improves athletic performance in recreationally active young males. However, the precise mechanism is not clear and future studies are needed. Acknowledgment: This research has been co‐financed by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH – CREATE – INNOVATE (project code:T2EDK-00843).

Keywords: sports performance, ergogenic supplements, nitrate, extract fractions

Procedia PDF Downloads 43
225 Substitutional Inference in Poetry: Word Choice Substitutions Craft Multiple Meanings by Inference

Authors: J. Marie Hicks

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The art of the poetic conjoins meaning and symbolism with imagery and rhythm. Perhaps the reader might read this opening sentence as 'The art of the poetic combines meaning and symbolism with imagery and rhythm,' which holds a similar message, but is not quite the same. The reader understands that these factors are combined in this literary form, but to gain a sense of the conjoining of these factors, the reader is forced to consider that these aspects of poetry are not simply combined, but actually adjoin, abut, skirt, or touch in the poetic form. This alternative word choice is an example of substitutional inference. Poetry is, ostensibly, a literary form where language is used precisely or creatively to evoke specific images or emotions for the reader. Often, the reader can predict a coming rhyme or descriptive word choice in a poem, based on previous rhyming pattern or earlier imagery in the poem. However, there are instances when the poet uses an unexpected word choice to create multiple meanings and connections. In these cases, the reader is presented with an unusual phrase or image, requiring that they think about what that image is meant to suggest, and their mind also suggests the word they expected, creating a second, overlying image or meaning. This is what is meant by the term 'substitutional inference.' This is different than simply using a double entendre, a word or phrase that has two meanings, often one complementary and the other disparaging, or one that is innocuous and the other suggestive. In substitutional inference, the poet utilizes an unanticipated word that is either visually or phonetically similar to the expected word, provoking the reader to work to understand the poetic phrase as written, while unconsciously incorporating the meaning of the line as anticipated. In other words, by virtue of a word substitution, an inference of the logical word choice is imparted to the reader, while they are seeking to rationalize the word that was actually used. There is a substitutional inference of meaning created by the alternate word choice. For example, Louise Bogan, 4th Poet Laureate of the United States, used substitutional inference in the form of homonyms, malapropisms, and other unusual word choices in a number of her poems, lending depth and greater complexity, while actively engaging her readers intellectually with her poetry. Substitutional inference not only adds complexity to the potential interpretations of Bogan’s poetry, as well as the poetry of others, but provided a method for writers to infuse additional meanings into their work, thus expressing more information in a compact format. Additionally, this nuancing enriches the poetic experience for the reader, who can enjoy the poem superficially as written, or on a deeper level exploring gradations of meaning.

Keywords: poetic inference, poetic word play, substitutional inference, word substitution

Procedia PDF Downloads 203
224 Continuous Glucose Monitoring Systems and the Improvement in Hypoglycemic Awareness Post-Islet Transplantation: A Single-Centre Cohort Study

Authors: Clare Flood, Shareen Forbes

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Background: Type 1 diabetes mellitus (T1DM) is an autoimmune disorder affecting >400,000 people in the UK alone, with the global prevalence expected to double in the next decade. Islet transplant offers a minimally-invasive procedure with very low morbidity and almost no mortality, and is now as effective as whole pancreas transplant. The procedure was introduced to the UK in 2011 for patients with the most severe type 1 diabetes mellitus (T1DM) – those with unstable blood glucose, frequently occurring episodes of severe hypoglycemia and impaired awareness of hypoglycemia (IAH). Objectives: To evaluate the effectiveness of islet transplantation in improving glycemic control, reducing the burden of hypoglycemia and improving awareness of hypoglycemia through a single-centre cohort study at the Royal Infirmary of Edinburgh. Glycemic control and degree of hypoglycemic awareness will be determined and monitored pre- and post-transplantation to determine effectiveness of the procedure. Methods: A retrospective analysis of data collected over three years from the 16 patients who have undergone islet transplantation in Scotland. Glycated haemoglobin (HbA1c) was measured and continuous glucose monitoring systems (CGMS) were utilised to assess glycemic control, while Gold and Clarke score questionnaires tested IAH. Results: All patients had improved glycemic control following transplant, with optimal control seen visually at 3 months post-transplant. Glycemic control significantly improved, as illustrated by percentage time in hypoglycemia in the months following transplant (p=0.0211) and HbA1c (p=0.0426). Improved Clarke (p=0.0034) and Gold (p=0.0001) scores indicate improved glycemic awareness following transplant. Conclusion: While the small sample of islet transplant recipients at the Royal Infirmary of Edinburgh prevents definitive conclusions being drawn, it is indicated that through our retrospective, single-centre cohort study of 16 patients, islet transplant is capable of improving glycemic control, reducing the burden of hypoglycemia and IAH post-transplant. Data can be combined with similar trials at other centres to increase statistical power but from research in Edinburgh, it can be suggested that the minimally invasive procedure of islet transplantation offers selected patients with extremely unstable T1DM the incredible opportunity to regain control of their condition and improve their quality of life.

Keywords: diabetes, islet, transplant, CGMS

Procedia PDF Downloads 247
223 The Connection between De Minimis Rule and the Effect on Trade

Authors: Pedro Mario Gonzalez Jimenez

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The novelties introduced by the last Notice on agreements of minor importance tighten the application of the ‘De minimis’ safe harbour in the European Union. However, the undetermined legal concept of effect on trade between the Member States becomes importance at the same time. Therefore, the current analysis that the jurist should carry out in the European Union to determine if an agreement appreciably restrict competition under Article 101 of the Treaty on the Functioning of the European Union is double. Hence, it is necessary to know how to balance the significance in competition and the significance in effect on trade between the Member States. It is a crucial issue due to the negative delimitation of restriction of competition affects the positive one. The methodology of this research is rather simple. Beginning with a historical approach to the ‘De Minimis Rule’, their main problems and uncertainties will be found. So, after the analysis of normative documents and the jurisprudence of the Court of Justice of the European Union some proposals of ‘Lege ferenda’ will be offered. These proposals try to overcome the contradictions and questions that currently exist in the European Union as a consequence of the current legal regime of agreements of minor importance. The main findings of this research are the followings: Firstly, the effect on trade is another way to analyze the importance of an agreement different from the ‘De minimis rule’. In point of fact, this concept is singularly adapted to go through agreements that have as object the prevention, restriction or distortion of competition, as it is observed in the most famous European Union case-law. Thanks to the effect on trade, as long as the proper requirements are met there is no a restriction of competition under article 101 of the Treaty on the Functioning of the European Union, even if the agreement had an anti-competitive object. These requirements are an aggregate market share lower than 5% on any of the relevant markets affected by the agreement and turnover lower than 40 million of Euros. Secondly, as the Notice itself says ‘it is also intended to give guidance to the courts and competition authorities of the Member States in their application of Article 101 of the Treaty, but it has no binding force for them’. This reality makes possible the existence of different statements among the different Member States and a confusing perception of what a restriction of competition is. Ultimately, damage on trade between the Member States could be observed for this reason. The main conclusion is that the significant effect on trade between Member States is irrelevant in agreements that restrict competition because of their effects but crucial in agreements that restrict competition because of their object. Thus, the Member States should propose the incorporation of a similar concept in their legal orders in order to apply the content of the Notice. Otherwise, the significance of the restrictive agreement on competition would not be properly assessed.

Keywords: De minimis rule, effect on trade, minor importance agreements, safe harbour

Procedia PDF Downloads 152
222 Tuberculosis (TB) and Lung Cancer

Authors: Asghar Arif

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Lung cancer has been recognized as one of the greatest common cancers, causing the annual mortality rate of about 1.2 million people in the world. Lung cancer is the most prevalent cancer in men and the third-most common cancer among women (after breast and digestive cancers).Recent evidences have shown the inflammatory process as one of the potential factors of cancer. Tuberculosis (TB), pneumonia, and chronic bronchitis are among the most important inflammation-inducing factors in the lungs, among which TB has a more profound role in the emergence of cancer.TB is one of the important mortality factors throughout the world, and 205,000 death cases are reported annually due to this disease. Chronic inflammation and fibrosis due to TB can induce genetic mutation and alternations. Parenchyma tissue of lung is involved in both diseases of TB and lung cancer, and continuous cough in lung cancer, morphological vascular variations, lymphocytosis processes, and generation of immune system mediators such as interleukins, are all among the factors leading to the hypothesis regarding the role of TB in lung cancer Some reports have shown that the induction of necrosis and apoptosis or TB reactivation, especially in patients with immune-deficiency, may result in increasing IL-17 and TNF_α, which will either decrease P53 activity or increase the expression of Bcl-2, decrease Bax-T, and cause the inhibition of caspase-3 expression due to decreasing the expression of mitochondria cytochrome oxidase. It has been also indicated that following the injection of BCG vaccine, the host immune system will be reinforced, and in particular, the rates of gamma interferon, nitric oxide, and interleukin-2 are increased. Therefore, CD4 + lymphocyte function will be improved, and the person will be immune against cancer.Numerous prospective studies have so far been conducted on the role of TB in lung cancer, and it seems that this disease is effective in that particular cancer.One of the main challenges of lung cancer is its correct and timely diagnosis. Unfortunately, clinical symptoms (such as continuous cough, hemoptysis, weight loss, fever, chest pain, dyspnea, and loss of appetite) and radiological images are similar in TB and lung cancer. Therefore, anti-TB drugs are routinely prescribed for the patients in the countries with high prevalence of TB, like Pakistan. Regarding the similarity in clinical symptoms and radiological findings of lung cancer, proper diagnosis is necessary for TB and respiratory infections due to nontuberculousmycobacteria (NTM). Some of the drug resistive TB cases are, in fact, lung cancer or NTM lung infections. Acid-fast staining and histological study of phlegm and bronchial washing, culturing and polymerase chain reaction TB are among the most important solutions for differential diagnosis of these diseases. Briefly, it is assumed that TB is one of the risk factors for cancer. Numerous studies have been conducted in this regard throughout the world, and it has been observed that there is a significant relationship between previous TB infection and lung cancer. However, to prove this hypothesis, further and more extensive studies are required. In addition, as the clinical symptoms and radiological findings of TB, lung cancer, and non-TB mycobacteria lung infections are similar, they can be misdiagnosed as TB.

Keywords: TB and lung cancer, TB people, TB servivers, TB and HIV aids

Procedia PDF Downloads 49
221 The Evaluation of a Novel Cardiac Index derived from Anthropometric and Biochemical Parameters in Pediatric Morbid Obesity and Metabolic Syndrome

Authors: Mustafa Metin Donma

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Metabolic syndrome (MetS) components are noteworthy among children with obesity and morbid obesity because they point out the cases with MetS, which have the great tendency to severe health problems such as cardiovascular diseases both in childhood and adulthood. In clinical practice, considerable efforts are being observed to bring into the open the striking differences between morbid obese cases and those with MetS findings. The most privileged aspect is concerning cardiometabolic features. The aim of this study was to derive an index which behaves different in children with and without MetS from the cardiac point of view. For the purpose, aspartate transaminase (AST), a cardiac enzyme still being used independently to predict cardiac-related problems, was used. One hundred and twenty four children were recruited from the outpatient clinic of Department of Pediatrics in Tekirdag Namik Kemal University, Faculty of Medicine. Forty-three children with normal body mass index, forty-one and forty morbid obese (MO) children with MetS and without the characteristic features of MetS, respectively, were included in the study. Weight, height, waist circumference (WC), hip C (HC), head C (HdC), neck C (NC), systolic and diastolic blood pressure values were measured and recorded. Body mass index and anthropometric ratios were calculated. Fasting blood glucose (FBG), insulin (INS), triglycerides (TRG), high density lipoprotein cholesterol (HDL-C) analyses were performed. The values for AST, alanin transaminase (ALT) and AST/ALT were obtained. Advanced Donma cardiac index (ADCI) values were calculated. The formula for the index was [(TRG/HDL-C) * (INS/FBG)] * [(WC+HC)/Height] * [(HdC+NC)/Height]. Statistical evaluations including correlation analysis were done by a statistical package program. The statistical significance degree was accepted as p<0.05. The index, ADCI, was developed from both anthropometric and biochemical parameters. All anthropometric measurements except weight were included in the equation. Besides all biochemical parameters concerning MetS components were also added. This index was tested in each of three groups. Its performance was compared with the performance of cardiometabolic index (CMI). It was also checked whether it was compatible with AST activity. The performance of ADCI was better than that of CMI. Instead of double increase, the increase of three times was observed in children with MetS compared to MO children. The index was correlated with AST in MO group and with AST/ALT in MetS group. In conclusion, this index was superior in discovering cardiac problems in MO and in diagnosing MetS in MetS groups. It was also arbiter to point out cardiovascular and MetS aspects among the groups.

Keywords: aspartate transaminase, cardiac, children, index, obesity

Procedia PDF Downloads 37
220 Mannose-Functionalized Lipopolysaccharide Nanoparticles for Macrophage-Targeted Dual Delivery of Rifampicin and Isoniazid

Authors: Mumuni Sumaila, Viness Pillay, Yahya E. Choonara, Pradeep Kumar, Pierre P. Kondiah

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Tuberculosis (TB) remains a serious challenge to public health globally, despite every effort put together to curb the disease. Current TB therapeutics available have proven to be inefficient due to a multitude of drawbacks that range from serious adverse effects/drug toxicity to inconsistent bioavailability, which ultimately contributes to the emergence of drug-resistant TB. An effective ‘cargo’ system designed to cleverly deliver therapeutic doses of anti-TB drugs to infection sites and in a sustained-release manner may provide a better therapeutic choice towards winning the war against TB. In the current study, we investigated mannose-functionalized lipopolysaccharide hybrid nanoparticles for safety and efficacy towards macrophage-targeted simultaneous delivery of the two first-line anti-TB drugs, rifampicin (RF) and isoniazid (IS). RF-IS-loaded lipopolysaccharide hybrid nanoparticles were fabricated using the solvent injection technique (SIT), incorporating soy lecithin (SL) and low molecular weight chitosan (CS) as the lipid and polysaccharide components, respectively. Surface-functionalized nanoparticles were obtained through the reaction of the aldehyde group of mannose with free amine functionality present at the surface of the nanoparticles. The functionalized nanocarriers were spherical with average particle size and surface charge of 107.83 nm and +21.77 mV, respectively, and entrapment efficiencies (EE) were 53.52% and 69.80% for RF and IS, respectively. FTIR spectrum revealed high-intensity bands between 1663 cm⁻¹ and 1408 cm⁻¹ wavenumbers (absent in non-functionalized nanoparticles), which could be attributed to the C=N stretching vibration produced by the formation of Schiff’s base (–N=CH–) during the mannosylation reaction. In vitro release studies showed a sustained-release profile for RF and IS, with less than half of the total payload released over a 48-hour period. The nanocarriers were biocompatible and safe, with more than 80% cell viability achieved when incubated with RAW 264.7 cells at concentrations 30 to 500 μg/mL over a 24-hour period. Cellular uptake studies (after a 24-hour incubation period with the murine macrophage cells, RAW 264.7) revealed a 13- and a 9-fold increase in intracellular accumulation of RF and IS, respectively, when compared with the unformulated RF+IS solution. A 6- and a 3-fold increase in intracellular accumulation of RF and IS, respectively, were observed when compared with the non-functionalized nanoparticles. Furthermore, fluorescent microscopy images showed nanoparticle internalization and accumulation within the RAW 264.7 cells, which was more significant in the mannose-functionalized system compared to the non-functionalized nanoparticles. The overall results suggested that the fabricated mannose-functionalized lipopolysaccharide nanoparticles are a safe and promising platform for macrophage-targeted delivery of anti-TB therapeutics. However, in vivo pharmacokinetic/pharmacodynamics studies are required to further substantiate the therapeutic efficacy of the nanosystem.

Keywords: anti-tuberculosis therapeutics, hybrid nanosystem, lipopolysaccharide nanoparticles, macrophage-targeted delivery

Procedia PDF Downloads 144
219 Layer-By-Layer Deposition of Poly (Amidoamine) and Poly (Acrylic Acid) on Grafted-Polylactide Nonwoven with Different Surface Charge

Authors: Sima Shakoorjavan, Mahdieh Eskafi, Dawid Stawski, Somaye Akbari

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In this study, poly (amidoamine) dendritic material (PAMAM) and poly (acrylic acid) (PAA) as polycation and polyanion were deposited on surface charged polylactide (PLA) nonwoven to study the relationship of dye absorption capacity of layered-PLA with the number of deposited layers. To produce negatively charged-PLA, acrylic acid (AA) was grafted on the PLA surface (PLA-g-AA) through a chemical redox reaction with the strong oxidizing agent. Spectroscopy analysis, water contact measurement, and FTIR-ATR analysis confirm the successful grafting of AA on the PLA surface through the chemical redox reaction method. In detail, an increase in dye absorption percentage by 19% and immediate absorption of water droplets ensured hydrophilicity of PLA-g-AA surface; and the presence of new carbonyl bond at 1530 cm-¹ and a wide peak of hydroxyl between 3680-3130 cm-¹ confirm AA grafting. In addition, PLA as linear polyester can undergo aminolysis, which is the cleavage of ester bonds and replacement with amid bonds when exposed to an aminolysis agent. Therefore, to produce positively charged PLA, PAMAM as amine-terminated dendritic material was introduced to PLA molecular chains at different conditions; (1) at 60 C for 0.5, 1, 1.5, 2 hours of aminolysis and (2) at room temperature (RT) for 1, 2, 3, and 4 hours of aminolysis. Weight changes and spectrophotometer measurements showed a maximum in weight gain graph and K/S value curve indicating the highest PAMAM attachment at 60 C for 1 hour and RT for 2 hours which is considered as an optimum condition. Also, the emerging new peak around 1650 cm-1 corresponding to N-H bending vibration and double wide peak at around 3670-3170 cm-1 corresponding to N-H stretching vibration confirm PAMAM attachment in selected optimum condition. In the following, regarding the initial surface charge of grafted-PLA, lbl deposition was performed and started with PAA or PAMAM. FTIR-ATR results confirm chemical changes in samples due to deposition of the first layer (PAA or PAMAM). Generally, spectroscopy analysis indicated that an increase in layer number costed dye absorption capacity. It can be due to the partial deposition of a new layer on the previously deposited layer; therefore, the available PAMAM at the first layer is more than the third layer. In detail, in the case of layer-PLA starting lbl with negatively charged, having PAMAM as the first top layer (PLA-g-AA/PAMAM) showed the highest dye absorption of both cationic and anionic model dye.

Keywords: surface modification, layer-by-layer technique, dendritic materials, PAMAM, dye absorption capacity, PLA nonwoven

Procedia PDF Downloads 61
218 Response of Caldeira De Tróia Saltmarsh to Sea Level Rise, Sado Estuary, Portugal

Authors: A. G. Cunha, M. Inácio, M. C. Freitas, C. Antunes, T. Silva, C. Andrade, V. Lopes

Abstract:

Saltmarshes are essential ecosystems both from an ecological and biological point of view. Furthermore, they constitute an important social niche, providing valuable economic and protection functions. Thus, understanding their rates and patterns of sedimentation is critical for functional management and rehabilitation, especially in an SLR scenario. The Sado estuary is located 40 km south of Lisbon. It is a bar built estuary, separated from the sea by a large sand spit: the Tróia barrier. Caldeira de Tróia is located on the free edge of this barrier, and encompasses a salt marsh with ca. 21,000 m². Sediment cores were collected in the high and low marshes and in the mudflat area of the North bank of Caldeira de Tróia. From the low marsh core, fifteen samples were chosen for ²¹⁰Pb and ¹³⁷Cs determination at University of Geneva. The cores from the high marsh and the mudflat are still being analyzed. A sedimentation rate of 2.96 mm/year was derived from ²¹⁰Pb using the Constant Flux Constant Sedimentation model. The ¹³⁷Cs profile shows a peak in activity (1963) between 15.50 and 18.50 cm, giving a 3.1 mm/year sedimentation rate for the past 53 years. The adopted sea level rise scenario was based on a model built with the initial rate of SLR of 2.1 mm/year in 2000 and an acceleration of 0.08 mm/year². Based on the harmonic analysis of Setubal-Tróia tide gauge of 2005 data, the tide model was estimated and used to build the tidal tables to the period 2000-2016. With these tables, the average mean water levels were determined for the same time span. A digital terrain model was created from LIDAR scanning with 2m horizontal resolution (APA-DGT, 2011) and validated with altimetric data obtained with a DGPS-RTK. The response model calculates a new elevation for each pixel of the DTM for 2050 and 2100 based on the sedimentation rates specific of each environment. At this stage, theoretical values were chosen for the high marsh and the mudflat (respectively, equal and double the low marsh rate – 2.92 mm/year). These values will be rectified once sedimentation rates are determined for the other environments. For both projections, the total surface of the marsh decreases: 2% in 2050 and 61% in 2100. Additionally, the high marsh coverage diminishes significantly, indicating a regression in terms of maturity.

Keywords: ¹³⁷Cs, ²¹⁰Pb, saltmarsh, sea level rise, response model

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217 Chinese Acupuncture: A Potential Treatment for Autism Rat Model via Improving Synaptic Function

Authors: Sijie Chen, Xiaofang Chen, Juan Wang, Yingying Zhang, Yu Hong, Wanyu Zhuang, Xinxin Huang, Ping Ou, Longsheng Huang

Abstract:

Purpose: Autistic symptom improvement can be observed in children treated with acupuncture, but the mechanism is still being explored. In the present study, we used scalp acupuncture to treat autism rat model, and then their improvement in the abnormal behaviors and specific mechanisms behind were revealed by detecting animal behaviors, analyzing the RNA sequencing of the prefrontal cortex(PFC), and observing the ultrastructure of PFC neurons under the transmission electron microscope. Methods: On gestational day 12.5, Wistar rats were given valproic acid (VPA) by intraperitoneal injection, and their offspring were considered to be reliable rat models of autism. They were randomized to VPA or VPA-acupuncture group (n=8). Offspring of Wistar pregnant rats that were simultaneously injected with saline were randomly selected as the wild-type group (WT). VPA_acupuncture group rats received acupuncture intervention at 23 days of age for 4 weeks, and the other two groups followed without intervention. After the intervention, all experimental rats underwent behavioral tests. Immediately afterward, they were euthanized by cervical dislocation, and their prefrontal cortex was isolated for RNA sequencing and transmission electron microscopy. Results: The main results are as follows: 1. Animal behavioural tests: VPA group rats showed more anxiety-like behaviour and repetitive, stereotyped behaviour than WT group rats. While VPA group rats showed less spatial exploration ability, activity level, social interaction, and social novelty preference than WT group rats. It was gratifying to observe that acupuncture indeed improved these abnormal behaviors of autism rat model. 2. RNA-sequencing: The three groups of rats differed in the expression and enrichment pathways of multiple genes related to synaptic function, neural signal transduction, and circadian rhythm regulation. Our experiments indicated that acupuncture can alleviate the major symptoms of ASD by improving these neurological abnormalities. 3. Under the transmission electron microscopy, several lysosomes and mitochondrial structural abnormalities were observed in the prefrontal neurons of VPA group rats, which were manifested as atrophy of the mitochondrial membran, blurring or disappearance of the mitochondrial cristae, and even vacuolization. Moreover, the number of synapses and synaptic vesicles was relatively small. Conversely, the mitochondrial structure of rats in the WT group and VPA_acupuncture was normal, and the number of synapses and synaptic vesicles was relatively large. Conclusion: Acupuncture effectively improved the abnormal behaviors of autism rat model and the ultrastructure of the PFC neurons, which might worked by improving their abnormal synaptic function, synaptic plasticity and promoting neuronal signal transduction.

Keywords: autism spectrum disorder, acupuncture, animal behavior, RNA sequencing, transmission electron microscope

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216 Heat Transfer Performance of a Small Cold Plate with Uni-Directional Porous Copper for Cooling Power Electronics

Authors: K. Yuki, R. Tsuji, K. Takai, S. Aramaki, R. Kibushi, N. Unno, K. Suzuki

Abstract:

A small cold plate with uni-directional porous copper is proposed for cooling power electronics such as an on-vehicle inverter with the heat generation of approximately 500 W/cm2. The uni-directional porous copper with the pore perpendicularly orienting the heat transfer surface is soldered to a grooved heat transfer surface. This structure enables the cooling liquid to evaporate in the pore of the porous copper and then the vapor to discharge through the grooves. In order to minimize the cold plate, a double flow channel concept is introduced for the design of the cold plate. The cold plate consists of a base plate, a spacer, and a vapor discharging plate, totally 12 mm in thickness. The base plate has multiple nozzles of 1.0 mm in diameter for the liquid supply and 4 slits of 2.0 mm in width for vapor discharging, and is attached onto the top surface of the porous copper plate of 20 mm in diameter and 5.0 mm in thickness. The pore size is 0.36 mm and the porosity is 36 %. The cooling liquid flows into the porous copper as an impinging jet flow from the multiple nozzles, and then the vapor, which is generated in the pore, is discharged through the grooves and the vapor slits outside the cold plate. A heated test section consists of the cold plate, which was explained above, and a heat transfer copper block with 6 cartridge heaters. The cross section of the heat transfer block is reduced in order to increase the heat flux. The top surface of the block is the grooved heat transfer surface of 10 mm in diameter at which the porous copper is soldered. The grooves are fabricated like latticework, and the width and depth are 1.0 mm and 0.5 mm, respectively. By embedding three thermocouples in the cylindrical part of the heat transfer block, the temperature of the heat transfer surface ant the heat flux are extrapolated in a steady state. In this experiment, the flow rate is 0.5 L/min and the flow velocity at each nozzle is 0.27 m/s. The liquid inlet temperature is 60 °C. The experimental results prove that, in a single-phase heat transfer regime, the heat transfer performance of the cold plate with the uni-directional porous copper is 2.1 times higher than that without the porous copper, though the pressure loss with the porous copper also becomes higher than that without the porous copper. As to the two-phase heat transfer regime, the critical heat flux increases by approximately 35% by introducing the uni-directional porous copper, compared with the CHF of the multiple impinging jet flow. In addition, we confirmed that these heat transfer data was much higher than that of the ordinary single impinging jet flow. These heat transfer data prove high potential of the cold plate with the uni-directional porous copper from the view point of not only the heat transfer performance but also energy saving.

Keywords: cooling, cold plate, uni-porous media, heat transfer

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215 A Galectin from Rock Bream Oplegnathus fasciatus: Molecular Characterization and Immunological Properties

Authors: W. S. Thulasitha, N. Umasuthan, G. I. Godahewa, Jehee Lee

Abstract:

In fish, innate immune defense is the first immune response against microbial pathogens which consists of several antimicrobial components. Galectins are one of the carbohydrate binding lectins that have the ability to identify pathogen by recognition of pathogen associated molecular patterns. Galectins play a vital role in the regulation of innate and adaptive immune responses. Rock bream Oplegnathus fasciatus is one of the most important cultured species in Korea and Japan. Considering the losses due to microbial pathogens, present study was carried out to understand the molecular and functional characteristics of a galectin in normal and pathogenic conditions, which could help to establish an understanding about immunological components of rock bream. Complete cDNA of rock bream galectin like protein B (rbGal like B) was identified from the cDNA library, and the in silico analysis was carried out using bioinformatic tools. Genomic structure was derived from the BAC library by sequencing a specific clone and using Spidey. Full length of rbGal like B (contig14775) cDNA containing 517 nucleotides was identified from the cDNA library which comprised of 435 bp in the open reading frame encoding a deduced protein composed of 145 amino acids. The molecular mass of putative protein was predicted as 16.14 kDa with an isoelectric point of 8.55. A characteristic conserved galactose binding domain was located from 12 to 145 amino acids. Genomic structure of rbGal like B consisted of 4 exons and 3 introns. Moreover, pairwise alignment showed that rock bream rbGal like B shares highest similarity (95.9 %) and identity (91 %) with Takifugu rubripes galectin related protein B like and lowest similarity (55.5 %) and identity (32.4 %) with Homo sapiens. Multiple sequence alignment demonstrated that the galectin related protein B was conserved among vertebrates. A phylogenetic analysis revealed that rbGal like B protein clustered together with other fish homologs in fish clade. It showed closer evolutionary link with Takifugu rubripes. Tissue distribution and expression patterns of rbGal like B upon immune challenges were performed using qRT-PCR assays. Among all tested tissues, level of rbGal like B expression was significantly high in gill tissue followed by kidney, intestine, heart and spleen. Upon immune challenges, it showed an up-regulated pattern of expression with Edwardsiella tarda, rock bream irido virus and poly I:C up to 6 h post injection and up to 24 h with LPS. However, In the presence of Streptococcus iniae rbGal like B showed an up and down pattern of expression with the peak at 6 - 12 h. Results from the present study revealed the phylogenetic position and role of rbGal like B in response to microbial infection in rock bream.

Keywords: galectin like protein B, immune response, Oplegnathus fasciatus, molecular characterization

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214 Pentosan Polysulfate Sodium: A Potential Treatment to Improve Bone and Joint Manifestations of Mucopolysaccharidosis I

Authors: Drago Bratkovic, Curtis Gravance, David Ketteridge, Ravi Krishnan, Michael Imperiale

Abstract:

The mucopolysaccharidoses (MPSs) are a group of lysosomal storage diseases that have a common defect in the catabolism of glycosaminoglycans (GAGs). MPS I is the most common of the MPS diseases. Manifestations of MPS I include coarsening of facial features, corneal clouding, developmental delay, short stature, skeletal manifestations, hearing loss, cardiac valve disease, hepatosplenomegaly, and umbilical and inguinal hernias. Treatments for MPS I restore or activate the missing or deficient enzyme in the case of enzyme replacement therapy (ERT) and haematopoietic stem cell transplantation (HSCT). Pentosan polysulfate sodium (PPS) is a potential treatment to improve bone and joint manifestations of MPS I. The mechanisms of action of PPS that are relevant to the treatment of MPS I are the ability to: (i) Reduce systemic and accumulated GAG, (ii) Reduce inflammatory effects via the inhibition of NF-kB, resulting in the reduction in pro-inflammatory mediators. (iii) Reduce the expression of the pain mediator nerve growth factor in osteocytes from degenerating joints. (iv) Inhibit the cartilage degrading enzymes related to joint dysfunction in MPS I. PPS is being evaluated as an adjunctive therapy to ERT and/or HSCT in an open-label, single-centre, phase 2 study. Patients are ≥ 5 years of age with a diagnosis of MPS I and previously received HSCT and/or ERT. Three white, female, patients with MPS I-Hurler, ages 14, 15, and 19 years, and one, white male patient aged 15 years are enrolled. All were diagnosed at ≤2 years of age. All patients received HSCT ≤ 6 months after diagnosis. Two of the patients were treated with ERT prior to HSCT, and 1 patient received ERT commencing 3 months prior to HSCT. Two patients received 0.75mg/kg and 2 patients received 1.5mg/kg of PPS. PPS was well tolerated at doses of 0.75 and 1.5 mg/kg to 47 weeks of continuous dosing. Of the 19 adverse events (AEs), 2 were related to PPS. One AE was moderate (pre-syncope) and 1 was mild (injection site bruising), experienced in the same patient. All AEs were reported as mild or moderate. There have been no SAEs. One subject experienced a COVID-19 infection and PPS was interrupted. The MPS I signature GAG fragments, sulfated disaccharide and UA-HNAc S, tended to decrease in 3 patients from baseline through Week 25. Week 25 GAG data are pending for the 4th patient. Overall, most biomarkers (inflammatory, cartilage degeneration, and bone turnover) evaluated in the 3 patients with 25-week assessments have indicated either no change or a reduction in levels compared to baseline. In 3 patients, there was a trend toward improvement in the 2MWT from baseline to Week 48 with > 100% increase in 1 patient (01-201). In the 3 patients that had Week 48 assessments, patients and proxies reported improvement in PGIC, including “worthwhile difference” (n=1), or “made all the difference” (n=2).

Keywords: MPS I, pentosan polysulfate sodium, clinical study, 2MWT, QoL

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