Search results for: interface treatment form

Authors: M. R. Vijayakumar, Sanjay Kumar Singh, Lakshmi, Hithesh Dewangan, Sanjay Singh

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Trans resveratrol (RES) is a natural molecule proved for cancer preventive and therapeutic activities devoid of any potential side effects. However, the therapeutic application of RES in disease management is limited because of its rapid elimination from blood circulation thereby low biological half life in mammals. Therefore, the main objective of this study is to enhance the circulation as well as therapeutic efficacy using PEGylated liposomes. D-α-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) is applied as steric surface decorating agent to prepare RES liposomes by thin film hydration method. The prepared nanoparticles were evaluated by various state of the art techniques such as dynamic light scattering (DLS) technique for particle size and zeta potential, TEM for shape, differential scanning calorimetry (DSC) for interaction analysis and XRD for crystalline changes of drug. Encapsulation efficiency and invitro drug release were determined by dialysis bag method. Cancer cell viability studies were performed by MTT assay, respectively. Pharmacokinetic studies were performed in sprague dawley rats. The prepared liposomes were found to be spherical in shape. Particle size and zeta potential of prepared formulations varied from 64.5±3.16 to 262.3±7.45 nm and -2.1 to 1.76 mV, respectively. DSC study revealed absence of potential interaction. XRD study revealed presence of amorphous form in liposomes. Entrapment efficiency was found to be 87.45±2.14 % and the drug release was found to be controlled up to 24 hours. Minimized MEC in MTT assay and tremendous enhancement in circulation time of RES PEGylated liposomes than its pristine form revealed that the stearic stabilized PEGylated liposomes can be an alternative tool to commercialize this molecule for chemopreventive and therapeutic applications in cancer.

Keywords: trans resveratrol, cancer nanotechnology, long circulating liposomes, bioavailability enhancement, liposomes for cancer therapy, PEGylated liposomes

Procedia PDF Downloads 589

Authors: Judith Stein, Elfriede Friedmann

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The injection of a drug into the vitreous body for the treatment of retinal diseases like wet aged-related macular degeneration (AMD) is the most common medical intervention worldwide. We develop mathematical models for drug transport in the vitreous body of a human eye to analyse the impact of different rheological models of the vitreous on drug distribution. In addition to the convection diffusion equation characterizing the drug spreading, we use porous media modeling for the healthy vitreous with a dense collagen network and include the steady permeating flow of the aqueous humor described by Darcy's law driven by a pressure drop. Additionally, the vitreous body in a healthy human eye behaves like a viscoelastic gel through the collagen fibers suspended in the network of hyaluronic acid and acts as a drug depot for the treatment of retinal diseases. In a completely liquefied vitreous, we couple the drug diffusion with the classical Navier-Stokes flow equations. We prove the global existence and uniqueness of the weak solution of the developed initial-boundary value problem describing the drug distribution in the healthy vitreous considering the permeating aqueous humor flow in the realistic three-dimensional setting. In particular, for the drug diffusion equation, results from the literature are extended from homogeneous Dirichlet boundary conditions to our mixed boundary conditions that describe the eye with the Galerkin's method using Cauchy-Schwarz inequality and trace theorem. Because there is only a small effective drug concentration range and higher concentrations may be toxic, the ability to model the drug transport could improve the therapy by considering patient individual differences and give a better understanding of the physiological and pathological processes in the vitreous.

Keywords: coupled PDE systems, drug diffusion, mixed boundary conditions, vitreous body

Procedia PDF Downloads 137

Authors: Soha A Soliman, Yasser A Ahmed, Mohamed A Khalaf

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Although the enormous literature describing the histology of the stomach of different avian species during the posthatching development, the available literature on the pre-hatching development of quail stomach development is scanty. Thus, the current study was undertaken to provide a careful description of the main histological events during the embryonic development of quail stomach. To achieve this aim, daily histological specimens from the stomach of quail of 4 days post-incubation till the day 17 (few hours before hatching) were examined with light microscopy. The current study showed that the primitive gut tube of the embryonic quail appeared at the 4th day post incubation, and both parts of stomach (proventriculus and gizzard) were similar in structure and composed of endodermal epithelium of pseudostratified type surrounded by undifferentiated mesenchymal tissue. The sequences of the developmental events in the gut tube were preceded in a cranio-caudal pattern. By the 5th day, the endodermal covering of the primitive proventriculus gave rise to sac-like invaginations. The primitive gizzard was distinguished into thick-walled bodies and thin-walled sacs. In the 6th day, the prospective proventricular glandular epithelium became canalized and the muscular layer was developed in the cranial part of the proventriculus, whereas the primitive muscular coat of the gizzard was represented by a layer of condensed mesenchyme. In the 7th day, the proventricular glandular epithelial invaginations increased in depth and number, while, the muscularis mucosa and the muscular layer began to be distinguished. In the 8th day, the myoblasts differentiated into spindle shaped smooth muscle fibers. In the 10th day, branching of the proventricular glands began. The branching continued later on. The surface and the glandular epithelium were transformed into simple columnar type in the 12th day. The epithelial covering of the gizzard gave rise to tubular invaginations lined by simple cuboidal epithelium and the surface epithelium became simple columnar. Canalization of the tubular glands was recognized in the 14th day. In the 15th day, the proventricular surface epithelium invaginated in an concentric manner around a central cavity to form immature secretory units. The central cavity was lined by eosinophilic cells which form the ductal epithelia. The peripheral lamellae were lined by basophilic cells; the undifferentiated oxyntico-peptic cells. Entero-endocrine cells stained positive for silver impregnation in the proventricular glands. The mucosal folding in the gizzard appeared in the 15th day to form the plicae and the sulci. The wall of the proventriculus and gizzard in the 17th day acquired the main histological features of post-hatching birds, but neither the surface nor the ductal epithelium were differentiated to mucous producing cells. The current results shoed be considered in the molecular developmental studies.

Keywords: quail, proventriculus, gizzard, pre-hatching, histology

Procedia PDF Downloads 616

Authors: Muhammad Badruzzaman, Alif Hasan, Md. Shahjahan

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Propiconazole is a triazole fungicide extensively used in agriculture which can harm to non-target organisms in aquatic environment through runoff. Chronic exposure to environmental pesticides turn to behavioral impairment in vertebrates including teleosts. However, the potential effect of this fungicide on neurobehavioral impairment and release from it in vertebrates has not been fully explored. In this work, we examined the role of melatonin to rescue fungicide induced neurobehavioral and reproductive alternation and its connection with changes in dopaminergic activity in the brain of Mystus cavasius. After fish were exposed to water containing propiconazole at 0, 0.1, 5, and 250 µg/L for 3 days, significant increases of DA, 3,4-dihydroxyphenylacetic acid (DOPAC; a DA metabolite), and their ratio (DOPAC/DA) were observed in whole brain at 250 µg/L concentration. When fish were treated with propiconazole at 250 µg/L for 3 days, there was a significant elevation of DA, DOPAC and DOPAC/DA in diencephalon and pituitary, and only DA in the telencephalon, compared with control fish. Besides, it induced a reduction in extracellular serotonin and had an anxiolytic-like effect, supported by a decrease in cortisol production. Increased locomotor activity, anxiety and aggressiveness, decreased gonadosomatic index with few vitellogenic oocytes in ovaries after propiconazole treatment. When fish were treated with melatonin, D1 (SCH-23390) or D2 (Haloperidol) dopamine receptor antagonists and combined of melatonin and D1/D2 receptor antagonist and was observed melatonin + D2 receptor antagonist rescued fungicide induced all behavioral changes in fish. These results indicate that propiconazole increases locomotor activity, anxiety and aggressiveness and decreases reproductive activity, which was rescued by combined treatment of melatonin and dopamine receptor antagonist.

Keywords: behavior, catfish, dopamine, fungicide, melatonin

Procedia PDF Downloads 115

Authors: Sadia H. Syeda, Zain H. Malik

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As systems continue to become more complex and the interdependencies of processes and sub-systems continue to grow and transform, the need for a comprehensive method of tracking and linking the lifecycle of the systems in a digital form becomes ever more critical. Digital Engineering (DE) provides an approach to managing an authoritative data source that links, tracks, and updates system data as it evolves and grows throughout the system development lifecycle. DE enables the developing, tracking, and sharing system data, models, and other related artifacts in a digital environment accessible to all necessary stakeholders. The DE environment provides an integrated electronic repository that enables traceability between design, engineering, and sustainment artifacts. The DE activities' primary objective is to develop a set of integrated, coherent, and consistent system models for the program. It is envisioned to provide a collaborative information-sharing environment for various stakeholders, including operational users, acquisition personnel, engineering personnel, and logistics and sustainment personnel. Examining the processes that DE can support in the systems engineering life cycle (SELC) is a primary step in the DE adoption and implementation journey. Through an analysis of the U.S Department of Defense’s (DoD) Office of the Secretary of Defense (OSD’s) Digital Engineering Strategy and their implementation, examples of DE implementation by the industry and technical organizations, this paper will provide descriptions of the current DE processes and best practices of implementing DE across an enterprise. This will help identify the capabilities, environment, and infrastructure needed to develop a potential roadmap for implementing DE practices consistent with its business strategy. A capability maturity matrix will be provided to assess the organization’s DE maturity emphasizing how all the SELC elements interlink to form a cohesive ecosystem. If implemented, DE can increase efficiency and improve the systems engineering processes' quality and outcomes.

Keywords: digital engineering, digital environment, digital maturity model, single source of truth, systems engineering life-cycle

Procedia PDF Downloads 92

Authors: Ying Li, Rui Hu, Shizhen Chen, Xin Zhou, Yunhuang Yang

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Prostate cancer is one of the leading causes of cancer-related death among men. Prostate-specific antigen (PSA), a specific product of prostatic epithelial cells, is an important indicator of prostate cancer. Though PSA is not a specific serum biomarker for the screening of prostate cancer, it is recognized as an indicator for prostate cancer recurrence and response to therapy for patient’s post-prostatectomy. Since radical prostatectomy eliminates the source of PSA production, serum PSA levels fall below 50 pg/mL, and may be below the detection limit of clinical immunoassays (current clinical immunoassay lower limit of detection is around 10 pg/mL). Many clinical studies have shown that intervention at low PSA levels was able to improve patient outcomes significantly. Therefore, ultra-sensitive and precise assays that can accurately quantify extremely low levels of PSA (below 1-10 pg/mL) will facilitate the assessment of patients for the possibility of early adjuvant or salvage treatment. Currently, the commercially available ultra-sensitive ELISA kit (not used clinically) can only reach a detection limit of 3-10 pg/mL. Other platforms developed by different research groups could achieve a detection limit as low as 0.33 pg/mL, but they relied on sophisticated instruments to get the final readout. Herein we report a microfluidic platform for point-of-care (POC) detection of PSA with a detection limit of 0.5 pg/mL and without the assistance of any equipment. This platform is based on a previously reported volumetric-bar-chart chip (V-Chip), which applies platinum nanoparticles (PtNPs) as the ELISA probe to convert the biomarker concentration to the volume of oxygen gas that further pushes the red ink to form a visualized bar-chart. The length of each bar is used to quantify the biomarker concentration of each sample. We devised a long reading channel V-Chip (LV-Chip) in this work to achieve a wide detection window. In addition, LV-Chip employed a unique enzyme-free ELISA probe that enriched PtNPs significantly and owned 500-fold enhanced catalytic ability over that of previous V-Chip, resulting in a significantly improved detection limit. LV-Chip is able to complete a PSA assay for five samples in 20 min. The device was applied to detect PSA in 50 patient serum samples, and the on-chip results demonstrated good correlation with conventional immunoassay. In addition, the PSA levels in finger-prick whole blood samples from healthy volunteers were successfully measured on the device. This completely stand-alone LV-Chip platform enables convenient POC testing for patient follow-up in the physician’s office and is also useful in resource-constrained settings.

Keywords: point-of-care detection, microfluidics, PSA, ultra-sensitive

Procedia PDF Downloads 110

Authors: H. Hadjeris, R. B. Ghoul, Lekhlaf, M. Nebbal

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Introduction: Adenoid cystic carcinomas of the lacrimal gland or orbital cylindroma constitute the second cause of epithelial tumors of this gland. It is a malignant tumor usually developed at the expense of the salivary glands; its orbital location is exceptional. It is a rare clinical entity, formidable by its malignancy and local aggressiveness; the recurrence rate is high. Materials and methods: Clinical case: 63 years old woman who presents with irreducible no pulsatile painful left exophthalmos with inflammatory chemosis and a decrease in visual acuity with a moderate intracranial hypertension syndrome that has been evolving for 03 months. Antecedent; a biopsy of the tumor was made; the histological examination was in favor of an adenoid cystic carcinoma of the lacrimal gland. Lesion assessment: computed tomography and brain MRI: show an intra and extra-conical mass; with sinus (ethmoido-frontal) and cerebral (left frontal) extension strongly enhanced after injection of contrast product surrounded by edema around the lesion, associated with left frontal bone lysis extension assessment: unremarkable treatment: Patient operated by left frontotemporal approach, a total exenteration was performed with macroscopically complete excision of the frontal lesion and wide frontal craniectomy with craniofacial reconstruction, followed by complementary radiotherapy. Results: The patient was seen again after 3 months in consultation; she does not present any signs in favor of a recurrence. Conclusion: Adenoid cystic carcinomas of the lacrimal gland are rare malignant tumors; they are very infiltrating and invasive. The prognosis is strongly linked to the treatment time.

Keywords: adenoid cystic, lacrimal gland, orbital location, fronto-temporal approac

Procedia PDF Downloads 71

Authors: Ehsan Ahmadifar

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In this research, the effects of different levels (control group (T0), (T1)1, (T2)2 and (T3)3 gr Inulin per Kg diet) of prebiotic Inulin as nutritional supplement on Danio rerio were investigated for 4 month. Since the beginning of feeding larvae until adult (average weight: 67.1 g, length: 4.5 cm) were fed with experimental diets. The survival rate of fish had no significant effect on rate survival (P > 0.05). The highest food conversion ratio (FCR) was in control group and the lowest was observed in T3. Treatment of T3 significantly caused the best feed conversion ratio in Zebra fish (P < 0.05). By increasing the inulin diet during the experiment, specific growth rate increased. The highest and the lowest body weight gain and condition factor were observed in T3 and control, respectively (P < 0.05). Adding 3 gr inulin in Zebra fish diet can improve the performance of the growth indices and final biomass, also this prebiotic can be considered as a suitable supplement for Cyprinidae diet. In the first sampling stage for feeding fish, fat and muscle protein was significantly higher than the second sampling stage (P < 0.05). Given that the second stage fish were full sexual maturity, the amount of fat in muscle decreased (P < 0.05). Moisture and ash levels were significantly (P < 0.05) higher in the second stage sampling than the first stage. Overall, different stage of living affected on muscle chemical composition muscle. Reproductive performance in treatment T2 and T3 were significantly higher than other treatments (P < 0.05). According to the results, the prebiotic inulin does not have a significant impact on the sex ratio in zebrafish (P > 0.05). Based on histology of the gonads, the use of dietary inulin accelerates the process of gonad development in zebrafish.

Keywords: inulin, zebrafish, reproduction, histology

Procedia PDF Downloads 305

Authors: Ngonidzashe Moyo, Mmaditshaba Rapatsa

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The primary objective of this study was to determine heavy metal contamination in the water, sediment, grass and fish in Sand River, South Africa. This river passes through an urban area and sewage effluent is discharged into it. Water from the Sand river is subsequently used for irrigation downstream of the sewage treatment works. The suitability of this water and the surrounding boreholes for irrigation was determined. This study was undertaken between January, 2014 and January, 2015. Monthly samples were taken from four sites. Sites 1 was upstream of the Polokwane Wastewater Treatment Plant, sites 2, 3 and 4 were downstream. Ten boreholes in the vicinity of the Sand River were randomly selected and the water was tested for heavy metal contamination. The concentration of heavy metals in Sand River water followed the order Mn>Fe>Pb>Cu≥Zn≥Cd. Manganese concentration averaged 0.34 mg/L. Heavy metal concentration in the sediment, grass and fish followed the order Fe>Mn>Zn>Cu>Pb>Cd. The bioaccumulation factor from grass to fish was highest in manganese (19.25), followed by zinc (16.39) and iron (14.14). Soil permeability index (PI) and sodium adsorption ratio (SAR) were used to determine the suitability of Sand River and borehole water for irrigation. The PI index for Sand River water was 75.1% and this indicates that Sand River water is suitable for irrigation of crops. The PI index for the borehole water ranged from 65.8-72.8% and again this indicates suitability of borehole water for crop irrigation. The sodium adsorption ratio also indicated that both Sand River and borehole water were suitable for irrigation. A risk assessment study is recommended to determine the suitability of the fish for human consumption.

Keywords: bioaccumulation, bioavailability, heavy metals, sodium adsorption ratio

Procedia PDF Downloads 223

Authors: Chanya Inprasit, Yi-Wen Lin

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Inflammation causes changes of peripheral and central nervous system properties, affecting both neuronal and non-neuronal cells, resulting in inflammatory pain. Acupoint injection (AI) was developed in the 1950s and has been widely used for relieving pain. It is an acupoint-stimulating technique that utilizes anatomically based meridians derived from Chinese medicine theory. AI has been accepted as an effective treatment and is thought to display superior results when compared to traditional acupuncture methods. However, the mechanism of AI needs to be ratified by more scientific evidence in order to support the theory and its therapeutic development. In this study, we explored the effect of AI on the comorbidity of chronic pain and depression. Mice hindpaw was injected by complete Freund’s adjuvant (CFA) to induce the condition of chronic pain. Measurements of mechanical and thermal hyperalgesia and depression-like behavior were analyzed. The results indicated a positive tendency to AI treatment. The comorbidity of chronic pain and depression was investigated with relation to transient receptor potential V1 (TRPV1) mechanism through the use of TRPV1 gene deletion. The expression of nociceptors such as voltage-gated sodium channels (Navs) or TRPV1, was significantly down-regulated by AI. The expression of inflammation-activated molecules: astrocytic marker glial fibrillary acidic protein (GFAP), the microglial marker Iba-1, S100B, and related kinases, were reversed by AI in both the peripheral and central nervous system. Taken together, these data provided a detailed molecular mechanism of AI-induced analgesia and anti-inflammatory properties. This finding may be utilized for clinical practice to treat chronic pain and depression comorbidity.

Keywords: inflammatory pain, acupoint injection, TRPV1, GFAP, S100B

Procedia PDF Downloads 149

Authors: Devadrita Dey Sarkar

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Oxidosqualene cyclase is a membrane bound enzyme in which helps in the formation of steroid scaffold in higher organisms. In a highly selective cyclization reaction oxidosqualene cyclase forms LANOSTEROL with seven chiral centres starting from the linear substrate 2,3-oxidosqualene. In humans OSC in cholesterol biosynthesis it represents a target for the discovery of novel anticholesteraemic drugs that could complement the widely used statins. The enzyme oxidosqualene: lanosterol cyclase (OSC) represents a novel target for the treatment of hypercholesterolemia. OSC catalyzes the cyclization of the linear 2,3-monoepoxysqualene to lanosterol, the initial four-ringed sterol intermediate in the cholesterol biosynthetic pathway. OSC also catalyzes the formation of 24(S), 25-epoxycholesterol, a ligand activator of the liver X receptor. Inhibition of OSC reduces cholesterol biosynthesis and selectively enhances 24(S),25-epoxycholesterol synthesis. Through this dual mechanism, OSC inhibition decreases plasma levels of low-density lipoprotein (LDL)-cholesterol and prevents cholesterol deposition within macrophages. The recent crystallization of OSC identifies the mechanism of action for this complex enzyme, setting the stage for the design of OSC inhibitors with improved pharmacological properties for cholesterol lowering and treatment of atherosclerosis. While studying and designing the inhibitor of oxidosqulene cyclase, I worked on the pdb id of 1w6k which was the most worked on pdb id and I used several methods, techniques and softwares to identify and validate the top most molecules which could be acting as an inhibitor for oxidosqualene cyclase. Thus, by partial blockage of this enzyme, both an inhibition of lanosterol and subsequently cholesterol formation as well as a concomitant effect on HMG-CoA reductase can be achieved. Both effects complement each other and lead to an effective control of cholesterol biosynthesis. It is therefore concluded that 2,3-oxidosqualene cyclase plays a crucial role in the regulation of intracellular cholesterol homeostasis. 2,3-Oxidosqualene cyclase inhibitors offer an attractive approach for novel lipid-lowering agents.

Keywords: anticholesteraemic, crystallization, statins, homeostasis

Procedia PDF Downloads 351

Authors: P. Donnelly, G. Mitchell

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Traumatic Brain Injury (TBI) is a major contributor to the global burden of disease; despite its ubiquity, there is significant variation in diagnosis, prognosis, and treatment between clinicians. This study aims to examine the spectrum of approaches that currently exist at a Level 1 Trauma Centre in Australasia by surveying Emergency Physicians and Neurosurgeons on those aspects of mTBI. A pilot survey of 17 clinicians (Neurosurgeons, Emergency Physicians, and others who manage patients with mTBI) at a Level 1 Trauma Centre in Brisbane, Australia, was conducted. The objective of this study was to examine the importance these clinicians place on various elements in their approach to the diagnosis, prognostication, and treatment of mTBI. The data were summarised, and the descriptive statistics reported. Loss of consciousness and post-traumatic amnesia were rated as the most important signs or symptoms in diagnosing mTBI (median importance of 8). MRI was the most important imaging modality in diagnosing mTBI (median importance of 7). ‘Number of the Previous TBIs’ and Intracranial Injury on Imaging’ were rated as the most important elements for prognostication (median importance of 9). Education and reassurance were rated as the most important modality for treating mTBI (median importance of 7). There was a statistically insignificant variation between the specialties as to the importance they place on each of these components. In this Australian tertiary trauma center, there appears to be variation in how clinicians approach mTBI. This study is underpowered to state whether this is between clinicians within a specialty or a trend between specialties. This variation is worthwhile in investigating as a step toward a unified approach to diagnosing, prognosticating, and treating this common pathology.

Keywords: mild traumatic brain injury, adult, clinician, survey

Procedia PDF Downloads 130

Authors: Mouna Baassi, Mohamed Moussaoui, Hatim Soufi, Sanchaita RajkhowaI, Ashwani Sharma, Subrata Sinha, Said Belaaouad

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Human Immunodeficiency Virus type 1 protease (HIV-1 PR) is one of the most challenging targets of antiretroviral therapy used in the treatment of AIDS-infected people. The performance of protease inhibitors (PIs) is limited by the development of protease mutations that can promote resistance to the treatment. The current study was carried out using statistics and bioinformatics tools. A series of thirty-three compounds with known enzymatic inhibitory activities against HIV-1 protease was used in this paper to build a mathematical model relating the structure to the biological activity. These compounds were designed by software; their descriptors were computed using various tools, such as Gaussian, Chem3D, ChemSketch and MarvinSketch. Computational methods generated the best model based on its statistical parameters. The model’s applicability domain (AD) was elaborated. Furthermore, one compound has been proposed as efficient against HIV-1 protease with comparable biological activity to the existing ones; this drug candidate was evaluated using ADMET properties and Lipinski’s rule. Molecular Docking performed on Wild Type and Mutant Type HIV-1 proteases allowed the investigation of the interaction types displayed between the proteases and the ligands, Darunavir (DRV) and the new drug (ND). Molecular dynamics simulation was also used in order to investigate the complexes’ stability, allowing a comparative study of the performance of both ligands (DRV & ND). Our study suggested that the new molecule showed comparable results to that of Darunavir and may be used for further experimental studies. Our study may also be used as a pipeline to search and design new potential inhibitors of HIV-1 proteases.

Keywords: QSAR, ADMET properties, molecular docking, molecular dynamics simulation.

Procedia PDF Downloads 40

Authors: Ramesh Chinnasamy, Srishti Semalty, Vishnu S. Nair, Thirumurugan Vedagiri, Mahesh Ganeshan, Gautam Talukdar, Karthy Sivapushanam, Abhijit Das

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Snakes form an integral component of ecological systems. Human population explosion and associated acceleration of habitat destruction and degradation, has led to a rapid increase in human-snake encounters. The study aims at understanding the level of awareness, knowledge, and attitude of the people towards human-snake negative interaction and role of awareness programmes in the Moyar river valley, Tamil Nadu. The study area is part of the Mudumalai and the Sathyamangalam Tiger Reserves, which are significant wildlife corridors between the Western Ghats and the Eastern Ghats in the Nilgiri Biosphere Reserve. The data was collected using questionnaire covering 644 respondents spread across 18 villages between 2018 and 2019. The study revealed that 86.5% of respondents had strong negative perceptions towards snakes which were propelled by fear, superstitions, and threat of snakebite which was common and did not vary among different villages (F=4.48; p = <0.05) and age groups (X2 = 1.946; p = 0.962). Cobra 27.8% (n = 294) and rat snake 21.3% (n = 225) were the most sighted species and most snake encounter occurred during the monsoon season i.e., July 35.6 (n = 218), June 19.1% (n = 117) and August 18.4% (n = 113). At least 1 out of 5 respondents was reportedly bitten by snakes during their lifetime. The most common species of snakes that were the cause of snakebite were Saw scaled viper (32.6%, n = 42) followed by Cobra 17.1% (n = 22). About 21.3% (n = 137) people reported livestock loss due to pythons and other snakes 21.3% (n = 137). Most people, preferred medical treatment for snakebite (87.3%), whereas 12.7%, still believed in traditional methods. The majority (82.3%) used precautionary measure by keeping traditional items such as garlic, kerosene, and snake plant to avoid snakes. About 30% of the respondents expressed need for technical and monetary support from the forest department that could aid in reducing the human-snake conflict. It is concluded that the general perception in the study area is driven by fear and negative attitude towards snakes. Though snakes such as Cobra were widely worshiped in the region, there are still widespread myths and misconceptions that have led to the irrational killing of snakes. Awareness and innovative education programs rooted in the local context and language should be integrated at the village level, to minimize risk and the associated threat of snakebite among the people. Results from this study shall help policy makers to devise appropriate conservation measures to reduce human-snake conflicts in India.

Keywords: Envenomation, Health-Education, Human-Wildlife Conflict, Neglected Tropical Disease, Snakebite Mitigation, Traditional Practitioners

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Authors: Ahmed A. D. Sarhan, M. Sayuti, M. Hamdi

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Due to rapid consumption of world's fossil fuel resources and impracticality of large-scale application and production of renewable energy, the significance of energy efficiency improvement of current available energy modes has been widely realized by both industry and academia. In the CNC machining field, the key solution for this issue is by increasing the effectiveness of the existing lubrication systems as it could reduce the power required to overcome the friction component in machining process. For more improvement, introducing the nanolubrication could produce much less power consumption as the rolling action of billions units of nanoparticle in the tool chip interface could reduce the cutting forces significantly. In this research, the possibility of using carbon onion nanolubrication with DLC cutting tool is investigated to reduce the machining power consumption. Carbon onion nanolubrication has been successfully developed with high tribology performance and mixed with ordinary mineral oil. The proper sonification method is used to provide a way to mix and suspend the particles thoroughly and efficiently. Furthermore, Diamond-Like Carbon (DLC) cutting tool is used and expected to play significant role in reducing friction and cutting forces and increasing abrasion resistance. The results showed significant reduction of the cutting force and the working power compared with the other conditions of using carbon black and normal lubrication systems.

Keywords: carbon onion, nanolubrication, machining power consumption, DLC cutting tool

Procedia PDF Downloads 433

Authors: R. Botrugno, S Basyuni, G. Nugent, I. Jenkyn, A. Ferro, H. Bennett, C. Hjalmarsson, J. Chu, V. Santhanam

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This trainee led randomised controlled trial (RCT) aims to assess various outcomes for resorbable versus non-resorbable sutures for traumatic lacerations to the face. Within this trial of resorbable versus non-resorbable sutures for traumatic lacerations of the face (TORNFace), patient recruitment was facilitated by trainees who were employed at an NHS University Teaching Hospital in the United Kingdom. The trainees received appropriate training prior to recruiting patients for the trial. This included the completion of a national research e-learning module and face-to-face training that was provided locally. The locally delivered training provided an understanding of the eligibility criteria for the trial and the consent process. Existing trainee skills were utilised involving clinical photography to record baseline data and delivering the intervention based on the treatment arm selected. Eligible patients who required primary closure of traumatic lacerations of the face were randomised into one of two treatment arms. These comprised of resorbable (vicryl rapide) or non-resorbable sutures (ethilon). Primarily the cosmetic outcome was assessed. Secondary outcomes included: complications rates, health care economics, and patient-reported outcomes. Remote follow-up of recruited patients utilised photographs of the facial laceration which had received the intervention. These took place at 1 week, 3 months and 6 months post-intervention. This study aims to demonstrate an example of trainee-led research within the specialty of oral and maxillofacial surgery. The available data for the randomised controlled trial will also be presented.

Keywords: laceration, suture, trauma, trial

Procedia PDF Downloads 137

Authors: Joshi Manisha, Shivaram, Anand Vinekar, Tanya Susan Mathews, Yeshaswini Nagaraj

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Retinopathy of prematurity (ROP) is abnormal blood vessel development in the retina of the eye in a premature infant. The principal object of the invention is to provide a technique for detecting demarcation line and ridge detection for a given ROP image that facilitates early detection of ROP in stage 1 and stage 2. The demarcation line is an indicator of Stage 1 of the ROP and the ridge is the hallmark of typically Stage 2 ROP. Thirty Retcam images of Asian Indian infants obtained during routine ROP screening have been used for the analysis. A graphical user interface has been developed to detect demarcation line/ridge and to extract ground truth. This novel algorithm uses multilevel vessel enhancement to enhance tubular structures in the digital ROP images. It has been observed that the orientation of the demarcation line/ridge is normal to the direction of the blood vessels, which is used for the identification of the ridge/ demarcation line. Quantitative analysis has been presented based on gold standard images marked by expert ophthalmologist. Image based analysis has been based on the length and the position of the detected ridge. In image based evaluation, average sensitivity and positive predictive value was found to be 92.30% and 85.71% respectively. In pixel based evaluation, average sensitivity, specificity, positive predictive value and negative predictive value achieved were 60.38%, 99.66%, 52.77% and 99.75% respectively.

Keywords: ROP, ridge, multilevel vessel enhancement, biomedical

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Authors: Zerzouri Nora, Benalia Nadia, Bensiali Nadia

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This paper presents a grid-connected wind power generation scheme using Doubly Fed Induction Generator (DFIG). This can supply power at constant voltage and constant frequency with the rotor speed varying. This makes it suitable for variable speed wind energy application. The DFIG system consists of wind turbine, asynchronous wound rotor induction generator, and inverter with Space Vector Modulation (SVM) controller. In which the stator is connected directly to the grid and the rotor winding is in interface with rotor converter and grid converter. The use of back-to-back SVM converter in the rotor circuit results in low distortion current, reactive power control and operate at variable speed. Mathematical modeling of the DFIG is done in order to analyze the performance of the systems and they are simulated using MATLAB. The simulation results for the system are obtained and hence it shows that the system can operate at variable speed with low harmonic current distortion. The objective is to track and extract maximum power from the wind energy system and transfer it to the grid for useful work.

Keywords: Doubly Fed Induction Generator, Wind Energy Conversion Systems, Space Vector Modulation, distortion harmonics

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Authors: Simin Shahvazi, Sepideh Soltani, Seyed Mehdi Ahmadi, Russell J. De Souza, Amin Salehi-Abargouei

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Background and Objectives: Vitamin D has received attention for its potential to disrupt cancer processes such as attenuating cell proliferation and exacerbating differentiation and apoptosis. However, whether there exists a role for vitamin D in the treatment of prostate cancer specifically remains controversial. We systematically review the literature to assess whether supplementation with vitamin D influences PSA response and overall survival in patients with prostate cancer. Methods: We searched PubMed, Scopus, ISI Web of Science and Google scholar from inception through up to 10 September 2017 for both before-and-after and randomized trials that evaluated the effect of vitamin D supplementation on the prostate specific antigen (PSA) response rate in participants with prostate cancer. The DerSimonian and Laird, inverse-weighted random-effects model was used to pool effect estimates from the studies. Heterogeneity and potential publication bias were evaluated. Subgroup analyses were also performed. Results: Twenty-two studies (16 before-after and 6 randomized controlled trials) were found and included in meta-analysis. The analysis on controlled clinical trials revealed that PSA change from baseline [weighted mean difference (WMD) = -1.66 ng/ml, 95%CI: -0.69, 0.36, P= 0.543)], PSA response (RR=1.18, 95%CI: 0.97, 1.45, P=0.104) and mortality rate (risk ratio (RR) = 1.05, 95% CI: 0.81-1.36; P=0.713) was not significantly different between vitamin D supplementation and placebo groups. Single arm trials revealed that vitamin D supplementation had had a modest effect on PSA response rate: 19% of those enrolled had at least a 50% reduction in PSA by the end of treatment (95% CI: 7% to 31%; p=0.002). Conclusion: We found that vitamin D modestly increases the PSA response rate in single arm studies. No effect on serum PSA levels, PSA response and mortality was seen in randomized controlled clinical trials. It does not seem patients with prostate cancer benefit from vitamin D supplementation.

Keywords: mortality, prostatic neoplasms, PSA response, vitamin D

Procedia PDF Downloads 195

Authors: Mardiati Zain, Yetti Marlida, Elihasridas Elihasridas, Erpomen Erpomen, Andri Andri

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Background: Livestock productivity is greatly influenced by the energy and protein balance in diet. This study aimed to determine the energy and protein balance of male Simenthal cattle diet with protein and energy levels. The experimental design used was a randomized block design (RBD) 2x3x3 factorial design. There are two factors namely A level of energy diet that is 65% and 70% TDN. Factor B is a protein level of diet used were 10, 12 and 14% and each treatment is repeated three times. The weight of Simenthal cattle used ranged between 240 - 300 kg. Diet consisted of ammoniated rice straw and concentrated with ratio 40:60. Concentrate consisted of palm kernel cake, rice brain, cassava, mineral, and urea. The variables measured were digestibility of dry matter, organic matter and fiber, dry matter intake, daily gain, feed efficiency and blood characteristic. Results: There was no interaction between protein and energy level of diet on the nutrients intake (DM intake, OM intake, CP intake), weight gain and efficiency (P < 0.01). There was an interaction between protein and energy level of diet on digestibility (DM, OM, CP and allantoin urine (P > 0.01) Nutrients intake decreases with increasing levels of energy and protein diet, while nutrient digestibility, Avarage daily gain and feed efficiency increases with increasing levels of energy and protein diet. Conclusions: The result can be concluded that the best treatment was A2B1 which is energy level 70% TDN and protein 10%, where are dry matter intake 7.66 kg/d, daily gain 1.25 kg/d, feed efficiency 16.12%, and dry matter and organic matter digestibility 64.08 and 69.42% respectively.

Keywords: energy and protein ratio, simenthal cattle, rice straw ammoniated, digestibility

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Authors: Mohamad Kazem Zamani, Meldi Suhatril

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Soil improvement is one of the main concerns of each civil engineer who is working at soil mechanics and geotechnics. Grouting has been used as a powerful treatment for soil improving. In this paper, we have tried to review the grouting application base on grouts which is used and also we have tried to give a general view of grout applications and where and when can be used.

Keywords: cementious grouting, chemical grouting, soil improvement, civil engineering

Procedia PDF Downloads 518

Authors: S. Ben-Shabat, T. Turgeman, O. Leubinski, N. Roth-Bejerano, V. Kagan-Zur, Y. Sitrit

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The ectomycorrhizal (ECM) desert truffle Terfezia boudieri produces edible fruit bodies and forms symbiosis with its host plant Helianthemum sessiliflorum (Cistaceae) in the Negev desert of Israel. The symbiosis is vital for both partners' survival under desert conditions. Under desert habitat conditions, ECMs must form symbiosis before entering the dry season. To secure a successful encounter, in the course of evolution, both partners have responded by evolving special signals exchange that facilitates recognition. Members of the Cistaceae family serve as host plants for many important truffles. Conceivably, during evolution a common molecule present in Cistaceae plants was recruited to facilitate successful encounter with ectomycorrhizas. Arbuscular vesicular fungi (AM) are promiscuous in host preferences, in contrast, ECM fungi show specificity to host plants. Accordingly, we hypothesize that H. sessiliflorum secretes a chemotrophic-signaling, which is common to plants hosting ECM fungi belonging to the Pezizales. However, thus far no signaling molecules have been identified in ECM fungi. We developed a bioassay for chemotrophic activity. Fractionation of root exudates revealed a substance with chemotrophic activity and molecular mass of 534. Following the above concept, screening the transcriptome of Terfezia, grown under chemoattraction, discovered genes showing high homology to G proteins-coupled receptors of plant pathogens involved in positive chemotaxis and chemotaxis suppression. This study aimed to identify the active molecule using analytical methods (LC-MS, NMR etc.). This should contribute to our understanding of how ECM fungi communicate with their hosts in the rhizosphere. In line with the ability of Terfezia to form also endomycorrhizal symbiosis like AM fungi, analysis of the mechanisms may likewise be applicable to AM fungi. Developing methods to manipulate fungal growth by the chemoattractant can open new ways to improve inoculation of plants.

Keywords: chemotrophic signal, Helianthemum sessiliflorum, Terfezia boudieri, ECM

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Authors: E. M. Hoballah, M. Saber, A. Turky, N. Awad, A. M. Zaghloul

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Remediation of cultivated sewage soils in Egypt become an important aspect in last decade for having healthy crops and saving the human health. In this respect, a greenhouse experiment was conducted where contaminated sewage soil was treated with modified forms of 2% bentonite (T1), 2% kaolinite (T2), 1% bentonite+1% kaolinite (T3), 2% probentonite (T4), 2% prokaolinite (T5), 1% bentonite + 0.5% kaolinite + 0.5% rock phosphate (RP) (T6), 2% iron oxide (T7) and 1% iron oxide + 1% RP (T8). These materials were applied as remediative materials. Untreated soil was also used as a control. All soil samples were incubated for 2 months at 25°C at field capacity throughout the whole experiment. Carbon dioxide (CO2) efflux from both treated and untreated soils as a biomass indicator was measured through the incubation time and kinetic parameters of the best fitted models used to describe the phenomena were taken to evaluate the succession of sewaged soils remediation. The obtained results indicated that according to the kinetic parameters of used models, CO2 effluxes from remediated soils was significantly decreased compared to control treatment with variation in rate values according to type of remediation material applied. In addition, analyzed microbial biomass parameter showed that Ni and Zn were the most potential toxic elements (PTEs) that influenced the decreasing order of microbial activity in untreated soil. Meanwhile, Ni was the only influenced pollutant in treated soils. Although all applied materials significantly decreased the hazards of PTEs in treated soil, modified bentonite was the best treatment compared to other used materials. This work discussed different mechanisms taking place between applied materials and PTEs founded in the studied sewage soil.

Keywords: remediation, potential toxic elements, soil biomass, sewage

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Authors: A. Zaidi, F. Khelifi, R. Masmoudi, M. Bouhicha

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5 In order to eradicate the degradation of reinforced concrete structures due to the steel corrosion, professionals in constructions suggest using fiber reinforced polymers (FRP) for their excellent properties. Nevertheless, high temperatures may affect the bond between FRP bar and concrete, and consequently the serviceability of FRP-reinforced concrete structures. This paper presents a nonlinear numerical investigation using ADINA software to investigate the effect of the spacing between glass FRP (GFRP) bars embedded in concrete on circumferential thermal deformations and the distribution of radial thermal cracks in reinforced concrete beams submitted to high temperature variations up to 60 °C for asymmetrical problems. The thermal deformations predicted from nonlinear finite elements model, at the FRP bar/concrete interface and at the external surface of concrete cover, were established as a function of the ratio of concrete cover thickness to FRP bar diameter (c/d_b) and the ratio of spacing between FRP bars in concrete to FRP bar diameter (e/d_b). Numerical results show that the circumferential thermal deformations at the external surface of concrete cover are linear until cracking thermal load varied from 32 to 55 °C corresponding to the ratio of e/d_b varied from 1.3 to 2.3, respectively. However, for ratios e/d_b >2.3 and c/d_b >1.6, the thermal deformations at the external surface of concrete cover exhibit linear behavior without any cracks observed on the specified surface. The numerical results are compared to those obtained from analytical models validated by experimental tests.

Keywords: concrete beam, FRP bars, spacing effect, thermal deformation

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Authors: Ekramul Hoque, Zinat Ara Eakut Zarin, Ershad Ali

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The growth and development of explants is governed by the effect of nutrient medium. Ammonium nitrate (NH4NO3) as a major salt of stock solution-1 for the preparation of tissue culture medium. But, it has several demerits on human civilization. It is use for the preparation of bomb and other destructive activities. Hence, it is totally ban in our country. A new chemical was identified as a substitute of ammonium nitrate. The concentrations of the other ingredients of major and minor salt were modified from the MS medium. The formulation of new medium is totally different from the MS nutrient composition. The most widely use MS medium composition was used as first check treatment and MS powder (Duchefa Biocheme, The Netherland) was used as second check treatment. The experiments were carried out at the Department of Biotechnology, Sher-e-Bangla Agricultural University, Dhaka, Bangladesh. Two potato varieties viz. Diamant and Asterix were used as experimental materials. The regeneration potentiality of potato onto new medium was best as compare with the two check treatments. The traits -node number, leaf number, shoot length, root lengths were highest in new medium. The plantlets were healthy, robust and strong as compare to plantlets regenerated from check treatments. Three subsequent sub-cultures were made in the new medium to observe the growth pattern of plantlet. It was also showed the best performance in all the parameter under studied. The regenerated plantlet produced good quality minituber under field condition. Hence, it is concluded that, a new plant tissue culture medium as discovered from the Department of Biotechnology, Sher-e-Bangla Agricultural University, Dhaka, Bangladesh under the leadership of Professor Dr. Md. Ekramul Hoque.

Keywords: new medium, potato, regeneration, ammonium nitrate

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Authors: El Hadji Mamadou Sonko, Mbaye Mbéguéré, Cheikh Diop, Linda Strande

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In new approaches that are being developed for the treatment of sludge, the valorization of by-product is increasingly encouraged. In this perspective, Echinochloa pyramidalis has been successfully tested in Cameroon. Echinochloa pyramidalis is an efficient forage plant in the treatment of faecal sludge. It provides high removal rates and biosolids of high agronomic value. Thus in order to advise the use of this plant in planted drying beds in Senegal its comparison with the plants long been used in the field deserves to be carried out. That is the aim of this study showing the influence of the nature of the plants on the drainage, the purifying performances and the quality of the biosolids. Echinochloa pyramidalis, Typha australis, and Phragmites australis are the three macrophytes used in this study. The drainage properties of the beds were monitored through the frequency of clogging, the percentage of recovered leachate and the dryness of the accumulated sludge. The development of plants was followed through the measurement of the density. The purification performances were evaluated from the incoming raw sludge flows and the outflows of leachate for parameters such as Total Solids (TS), Total Suspended Solids (TSS), Total Volatile Solids (TVS), Chemical Oxygen Demand (COD), Total Kjeldahl Nitrogen (TKN), Ammonia (NH₄⁺), Nitrate (NO₃⁻), Total Phosphorus (TP), Orthophosphorus (PO₄³⁻) and Ascaris eggs. The quality of the biosolids accumulated on the beds was measured after 3 months of maturation for parameters such as dryness, C/N ratio NH₄⁺/NO₃⁻ ratio, ammonia, Ascaris eggs. The results have shown that the recovered leachate volume is about 40.4%; 45.6% and 47.3%; the dryness about 41.7%; 38.7% and 28.7%, and clogging frequencies about 6.7%; 8.2% and 14.2% on average for the beds planted with Echinochloa pyramidalis, Typha australis and Phragmites australis respectively. The plants of Echinochloa pyramidalis (198.6 plants/m²) and Phragmites australis (138 plants/m²) have higher densities than Typha australis (90.3 plants/m²). The nature of the plants has no influence on the purification performance with reduction percentages around 80% or more for all the parameters followed whatever the nature of the plants. However, the concentrations of these various leachate pollutants are above the limit values of the Senegalese standard NS 05-061 for the release into the environment. The biosolids harvested after 3 months of maturation are all mature with C/N ratios around 10 for all the macrophytes. The NH₄⁺/NO₃⁻ ratio is lower than 1 except for the biosolids originating from the Echinochloa pyramidalis beds. The ammonia is also less than 0.4 g/kg except for biosolids from Typha australis beds. Biosolids are also rich in mineral elements. Their concentrations of Ascaris eggs are higher than the WHO recommendations despite a percentage of inactivation around 80%. These biosolids must be stored for an additional time or composted. From these results, the use of Echinochloa pyramidalis as the main macrophyte can be recommended in the various drying beds planted in sub-Saharan climate conditions.

Keywords: faecal sludge, nature of plants, quality of biosolids, treatment performances

Procedia PDF Downloads 170

Authors: Abdul-Nasser El-Kassar, Walid Elgammal, Hisham Jawhar

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This paper studies the determinants of the dividends payout ratio. The factors affecting the dividends payout ratio are to be identified. The study focuses only on the cement and construction industry within the MENA region in an attempt to isolate any incoherent behavior. The factors under consideration are: sales growth, ROE, ROA, ROS, debt to equity ratio, firm size, and free cash flow. Data were collected from official stock exchange markets in addition to annual reports. The study considered all firms that paid dividend in each of the three consecutive years starting from 2010 till 2012. Out of the 123 listed firms that work in cement and construction industry in MENA region, only 19 paid dividends in the three consecutive years 2010-12. Our sample consists of the 19 firms (57 observations) which are selected according to purposive sampling. Moreover, the study uses the homogeneous subcategory within the purposive sampling since only similar firms in the construction industry had been examined. The outcome of the study provides a vital insight into the determinants of dividends payout ratio of companies in MENA region. The results showed that the dividend payout ratio has a strong and positive relationship with return on assets and strong but negative relationship with return on equity. On the other hand, the results detected weak relationships between dividend payout ratio and sale growth, debt to equity ratio, firm size, and free cash flow. The study suggests that board of directors tend to compensate shareholders and minimize the agency cost by distributing a high portion of profits in form of dividends whenever return on equity decreases. Also, when the performance of the firm improves, and hence return on assets increases, boards of directors are more generous in distributing profits.

Keywords: dividends payout ratio, profitability firm size, free cashflow, debt to equity ratio

Procedia PDF Downloads 364

Authors: Jose R. Garcia, Lexi Frankel, Amalia Ardeljan, Sergio Medina, Ali Yasback, Omar Rashid

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Background: Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that affects nearly half of the population worldwide and humans serve as the principal reservoir. Infection rates usually follow an inverse relationship with hygiene practices and are higher in developing countries than developed countries. Incidence varies significantly by geographic area, race, ethnicity, age, and socioeconomic status. H. pylori is primarily associated with conditions of the gastrointestinal tract such as atrophic gastritis and duodenal peptic ulcers. Infection is also associated with an increased risk of carcinogenesis as there is evidence to show that H. pylori infection may lead to gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT) lymphoma. It is suggested that H. pylori infection may be considered as a systemic condition, leading to various novel associations with several different neoplasms such as colorectal cancer, pancreatic cancer, and lung cancer, although further research is needed. Emerging evidence suggests that H. pylori infection may offer protective effects against Mycobacterium tuberculosis as a result of non-specific induction of interferon- γ (IFN- γ). Similar methods of enhanced immunity may affect the development of bronchogenic carcinoma due to the antiproliferative, pro-apoptotic and cytostatic functions of IFN- γ. The purpose of this study was to evaluate the correlation between Helicobacter pylori infection and the incidence of bronchogenic carcinoma. Methods: The data was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to evaluate the patients infected versus patients not infected with H. pylori using ICD-10 and ICD-9 codes. Access to the database was granted by the Holy Cross Health, Fort Lauderdale for the purpose of academic research. Standard statistical methods were used. Results:-Between January 2010 and December 2019, the query was analyzed and resulted in 163,224 in both the infected and control group, respectively. The two groups were matched by age range and CCI score. The incidence of bronchogenic carcinoma was 1.853% with 3,024 patients in the H. pylori group compared to 4.785% with 7,810 patients in the control group. The difference was statistically significant (p < 2.22x10-16) with an odds ratio of 0.367 (0.353 - 0.383) with a confidence interval of 95%. The two groups were matched by treatment and incidence of cancer, which resulted in a total of 101,739 patients analyzed after this match. The incidence of bronchogenic carcinoma was 1.929% with 1,962 patients in the H. pylori and treatment group compared to 4.618% with 4,698 patients in the control group with treatment. The difference was statistically significant (p < 2.22x10-16) with an odds ratio of 0.403 (0.383 - 0.425) with a confidence interval of 95%.

Keywords: bronchogenic carcinoma, helicobacter pylori, lung cancer, pathogen-associated molecular patterns

Procedia PDF Downloads 183

Authors: Evanka Madan, Madhu Puri, Dan Zilberstein, Rohini Muthuswami, Rentala Madhubala

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The extensive interaction between the host and pathogen metabolic networks decidedly shapes the outcome of infection. Utilization of arginine by the host and pathogen is critical for determining the outcome of pathogenic infection. Infections with L. donovani, an intracellular parasite, will lead to an extensive competition of arginine between the host and the parasite donovani infection. One of the major amino acid (AA) sensing signaling pathways in mammalian cells are the mammalian target of rapamycin complex I (mTORC1) pathway. mTORC1, as a sensor of nutrient, controls numerous metabolic pathways. Arginine is critical for mTORC1 activation. SLC38A9 is the arginine sensor for the mTORC1, being activated during arginine sufficiency. L. donovani transport arginine via a high-affinity transporter (LdAAP3) that is rapidly up-regulated by arginine deficiency response (ADR) in intracellular amastigotes. This study, to author’s best knowledge, investigates the interaction between two arginine sensing systems that act in the same compartment, the lysosome. One is important for macrophage defense, and the other is essential for pathogen virulence. We hypothesize that the latter modulates lysosome arginine to prevent host defense response. The work presented here identifies an upstream regulatory role of LdAAP3 in regulating the expression of SLC38A9-mTORC1 pathway, and consequently, their function in L. donovani infected THP-1 cells cultured in 0.1 mM and 1.5 mM arginine. It was found that in physiological levels of arginine (0.1 mM), infecting THP-1 with Leishmania leads to increased levels of SLC38A9 and mTORC1 via an increase in the expression of RagA. However, the reversal was observed with LdAAP3 mutants, reflecting the positive regulatory role of LdAAP3 on the host SLC38A9. At the molecular level, upon infection, mTORC1 and RagA were found to be activated at the surface of phagolysosomes which was found to form a complex with phagolysosomal localized SLC38A9. To reveal the relevance of SLC38A9 under physiological levels of arginine, endogenous SLC38A9 was depleted and a substantial reduction in the expression of host mTORC1, its downstream active substrate, p-P70S6K1 and parasite LdAAP3, was observed, thereby showing that silencing SLC38A9 suppresses ADR. In brief, to author’s best knowledge, these results reveal an upstream regulatory role of LdAAP3 in manipulating SLC38A9 arginine sensing in host macrophages. Our study indicates that intra-macrophage survival of L. donovani depends on the availability and transport of extracellular arginine. An understanding of the sensing pathway of both parasite and host will open a new perspective on the molecular mechanism of host-parasite interaction and consequently, as a treatment for Leishmaniasis.

Keywords: arginine sensing, LdAAP3, L. donovani, mTORC1, SLC38A9, THP-1

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Authors: Amokrane Boufares, Elise Provost, Veronique Osswald, Pascal Clain, Anthony Delahaye, Laurence Fournaison, Didier Dalmazzone

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Gas hydrates have long been considered as problematic for flow assurance in natural gas and oil transportation. On the other hand, they are now seen as future promising materials for various applications (i.e. desalination of seawater, natural gas and hydrogen storage, gas sequestration, gas combustion separation and cold storage and transport). Nonetheless, a better understanding of the crystallization mechanism of gas hydrate and of their formation kinetics is still needed for a better comprehension and control of the process. To that purpose, measuring the real-time evolution of the dissolved gas concentration in the aqueous phase during hydrate formation is required. In this work, CO₂ hydrates were formed in a stirred reactor equipped with an Attenuated Total Reflection (ATR) probe coupled to a Fourier Transform InfraRed (FTIR) spectroscopy analyzer. A method was first developed to continuously measure in-situ the CO₂ concentration in the liquid phase during solubilization, supersaturation, hydrate crystallization and dissociation steps. Thereafter, the measured concentration data were compared with those of equilibrium concentrations. It was observed that the equilibrium is instantly reached in the liquid phase due to the fast consumption of dissolved gas by the hydrate crystallization. Consequently, it was shown that hydrate crystallization kinetics is limited by the gas transfer at the gas-liquid interface. Finally, we noticed that the liquid-hydrate equilibrium during the hydrate crystallization is governed by the temperature of the experiment under the tested conditions.

Keywords: gas hydrate, dissolved gas, crystallization, infrared spectroscopy

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