Search results for: damage measures
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 5796

Search results for: damage measures

4686 Pioglitazone Ameliorates Methotrexate-Induced Renal Endothelial Dysfunction via Amending Detrimental Changes in Antioxidant Profile, Systemic Cytokines and Apoptotic Factors

Authors: Sahar M. El-Gowilly, Mai M. Helmy, Hanan M. El-Gowelli

Abstract:

Methotrexate (MTX) is widely used in treatment of cancers and autoimmune diseases. However, nephrotoxicity is one of the most important side effects of MTX. The peroxisome proliferator-activated receptor gamma agonist, pioglitazone (PIO), is known to exert anti-inflammatory and reno-protective effects in various kidney injuries. The purpose of this study was to investigate the potential involvement of endothelial damage in MTX-induced renal injury and to elaborate the possible protective effect of PIO against MTX-induced nephropathy. Compared with saline-treated rats, treatment with MTX (7 mg/kg for 3 day) caused significant elevations in serum levels of urea and creatinine, increased renal nitrate/nitrite level and impaired renovascular responsiveness of isolated perfused kidney to endothelium-dependent vasodilations induced by acetylcholine (0.01-2.43 nmol) and isoprenaline (1µmol). These effects were abolished by concurrent treatment with PIO (2.5 mg/kg, for 5 days starting two days before MTX). Alternatively, MTX treatment did not affect endothelium-independent renovascular relaxation induced by sodium nitroprusside (1-30 μmole). The possibility that alterations in renal antioxidants, circulating cytokine and apoptotic factor (Fas) levels contributed to MTX-PIO interaction was assessed. PIO treatment abrogated renal oxidative stress (decreased reduced glutathione and catalase activity and increased malondialdehyde), elevated serum cytokine (interleukin-6, interleukin-10, tumor necrosis factor-alpha and transforming growth factor-beta1) and Fas induced by MTX. Histologically, MTX caused defused tubular cells swelling and vacuolization associated with endothelial damage in renal arterioles. These effects disappeared upon co-treated with PIO. Collectively, PIO abolished MTX-induced endothelium dysfunction and nephrotoxicity via ameliorating oxidative stress and rectifying cytokines and Fas abnormalities caused by MTX.

Keywords: methotrexate, pioglitazone, endothelium, kidney

Procedia PDF Downloads 297
4685 Analysis of Cell Cycle Status in Radiation Non-Targeted Hepatoma Cells Using Flow Cytometry: Evidence of Dose Dependent Response

Authors: Sharmi Mukherjee, Anindita Chakraborty

Abstract:

Cellular irradiation incites complex responses including arrest of cell cycle progression. This article accentuates the effects of radiation on cell cycle status of radiation non-targeted cells. Human Hepatoma HepG2 cells were exposed to increasing doses of γ radiations (1, 2, 4, 6 Gy) and their cell culture media was transferred to non-targeted HepG2 cells cultured in other Petri plates. These radiation non-targeted cells cultured in the ICCM (Irradiated cell conditioned media) were the bystander cells on which cell cycle analysis was performed using flow cytometry. An apparent decrease in the distribution of bystander cells at G0/G1 phase was observed with increased radiation doses upto 4 Gy representing a linear relationship. This was accompanied by a gradual increase in cellular distribution at G2/M phase. Interestingly the number of cells in G2/M phase at 1 and 2 Gy irradiation was not significantly different from each other. However, the percentage of G2 phase cells at 4 and 6 Gy doses were significantly higher than 2 Gy dose indicating the IC50 dose to be between 2 and 4 Gy. Cell cycle arrest is an indirect indicator of genotoxic damage in cells. In this study, bystander stress signals through the cell culture media of irradiated cells disseminated the radiation induced DNA damages in the non-targeted cells which resulted in arrest of the cell cycle progression at G2/M phase checkpoint. This implies that actual radiation biological effects represent a penumbra with effects encompassing a larger area than the actual beam. This article highlights the existence of genotoxic damages as bystander effects of γ rays in human Hepatoma cells by cell cycle analysis and opens up avenues for appraisal of bystander stress communications between tumor cells. Contemplation of underlying signaling mechanisms can be manipulated to maximize damaging effects of radiation with minimum dose and thus has therapeutic applications.

Keywords: bystander effect, cell cycle, genotoxic damage, hepatoma

Procedia PDF Downloads 172
4684 Analyzing the Factors That Influence Students' Professional Identity Using Hierarchical Regression Analysis to Ease Higher Education Transition

Authors: Alba Barbara-i-Molinero, Rosalia Cascon Pereira, Ana Beatriz Hernandez Lara

Abstract:

Our general motivation in undertaking this study is to propose alternative measures to lighten students experienced tensions during the transitions from high school to higher education based on the concept of professional identity strength. In order to do so, we measured the influence that three different factors external motivational conditionals, educational experience conditionals and personal motivation conditionals exerted over students’ professional identity strength and proposed the measures considering the obtained results. By using hierarchical regression analysis we addressed this issue, across disciplines and bachelor degrees, allowing us to gain also deeper insight into first-year university students PID. Our findings suggest that students’ from the different disciplines are influenced by personal motivational conditionals; while students from sciences are also influenced by external motivational conditionals. Based on the obtained results we propose three different alternative educational and recruitment strategies which aim to increase students’ professional identity strength and reduce the tensions generated during high school-university transitions. From this study theoretical contributions regarding the differences in the influence of these factors on students from different bachelor degrees arise; and practical implications for universities, derived from the proposed strategies.

Keywords: professional identity, transitions, higher education, strategies

Procedia PDF Downloads 162
4683 Rosuvastatin Improves Endothelial Progenitor Cells in Rheumatoid Arthritis

Authors: Ashit Syngle, Nidhi Garg, Pawan Krishan

Abstract:

Background: Endothelial Progenitor Cells (EPCs) are depleted and contribute to increased cardiovascular (CV) risk in rheumatoid arthritis (RA). Statins exert a protective effect in CAD partly by promoting EPC mobilization. This vasculoprotective effect of statin has not yet been investigated in RA. We aimed to investigate the effect of rosuvastatin on EPCs in RA. Methods: 50 RA patients were randomized to receive 6 months of treatment with rosuvastatin (10 mg/day, n=25) and placebo (n=25) as an adjunct to existing stable antirheumatic drugs. EPCs (CD34+/CD133+) were quantified by Flow Cytometry. Inflammatory measures included DAS28, CRP and ESR were measured at baseline and after treatment. Lipids and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1) were estimated at baseline and after treatment. Results: At baseline, inflammatory measures and pro-inflammatory cytokines were elevated and EPCs depleted among both groups. At baseline, EPCs inversely correlated with DAS28 and TNF-α in both groups. EPCs increased significantly (p < 0.01) after treatment with rosuvastatin but did not show significant change with placebo. Rosuvastatin exerted positive effect on lipid spectrum: lowering total cholesterol, LDL, non HDL and elevation of HDL as compared with placebo. At 6 months, DAS28, ESR, CRP, TNF-α and IL-6 improved significantly in rosuvastatin group. Significant negative correlation was observed between EPCs and DAS28, CRP, TNF-α, and IL-6 after treatment with rosuvastatin. Conclusion: First study to show that rosuvastatin improves inflammation and EPC biology in RA possibly through its anti-inflammatory and lipid lowering effect. This beneficial effect of rosuvastatin may provide a novel strategy to prevent cardiovascular events in RA.

Keywords: RA, Endothelial Progenitor Cells, rosuvastatin, cytokines

Procedia PDF Downloads 246
4682 Design of a New Architecture of IDS Called BiIDS (IDS Based on Two Principles of Detection)

Authors: Yousef Farhaoui

Abstract:

An IDS is a tool which is used to improve the level of security.In this paper we present different architectures of IDS. We will also discuss measures that define the effectiveness of IDS and the very recent works of standardization and homogenization of IDS. At the end, we propose a new model of IDS called BiIDS (IDS Based on the two principles of detection).

Keywords: intrusion detection, architectures, characteristic, tools, security

Procedia PDF Downloads 449
4681 Pioglitazone Ameliorates Methotrexate-Induced Renal Endothelial Dysfunction via Amending Detrimental Changes in Antioxidant Profile, Systemic Cytokines and Fas Production

Authors: Sahar M. El-Gowilly, Mai M. Helmy, Hanan M. El-Gowelli

Abstract:

Methotrexate (MTX) is widely used in treatment of cancers and autoimmune diseases. However, nephrotoxicity is one of its most important side effects. The peroxisome proliferator-activated receptor gamma agonist, pioglitazone, is known to exert antiinflammatory and reno-protective effects in various kidney injuries. The purpose of this study was to investigate the potential involvement of endothelial damage in MTX-induced renal injury and to elaborate the possible protective effect of pioglitazone against MTX-induced endothelial impairment. Compared with saline-treated rats, treatment with MTX (7 mg/kg for 3 day) caused significant elevations in serum levels of urea and creatinine, increased renal nitrate/nitrite level and impaired renovascular responsiveness of isolated perfused kidney to endothelium-dependent vasodilations induced by acetylcholine (0.01-2.43 nmol) and isoprenaline (1µmol). These effects were abolished by concurrent treatment with pioglitazone (2.5 mg/kg, for 5 days starting two days before MTX). Alternatively, MTX treatment did not affect endothelium-independent renovascular relaxation induced by sodium nitroprusside (0.001-10 μmole). The possibility that alterations in renal antioxidants, circulating cytokine and apoptotic factor (Fas) levels contributed to MTX-pioglitazone interaction was assessed. Pioglitazone treatment abrogated renal oxidative stress (decreased reduced glutathione and catalase activity and increased malondialdehyde), elevated serum cytokine (interleukin-6, interleukin-10, tumor necrosis factor-alpha and transforming growth factor-beta1) and Fas induced by MTX. Histologically, MTX caused defused tubular cells swelling and vacuolization associated with endothelial damage in renal arterioles. These effects disappeared upon co-treated with pioglitazone. Collectively, pioglitazone abolished MTX-induced endothelium dysfunction and nephrotoxicity via ameliorating oxidative stress and rectifying cytokines and Fas abnormalities caused by MTX.

Keywords: methotrexate, pioglitazone, endothelium, kidney

Procedia PDF Downloads 485
4680 Mediating Role of 'Investment Recovery' and 'Competitiveness' on the Impact of Green Supply Chain Management Practices over Firm Performance: An Empirical Study Based on Textile Industry of Pakistan

Authors: Mehwish Jawaad

Abstract:

Purpose: The concept of GrSCM (Green Supply Chain Management) in the academic and research field is still thought to be in the development stage especially in Asian Emerging Economies. The purpose of this paper is to contribute significantly to the first wave of empirical investigation on GrSCM Practices and Firm Performance measures in Pakistan. The aim of this research is to develop a more holistic approach towards investigating the impact of Green Supply Chain Management Practices (Ecodesign, Internal Environmental Management systems, Green Distribution, Green Purchasing and Cooperation with Customers) on multiple dimensions of Firm Performance Measures (Economic Performance, Environmental Performance and Operational Performance) with a mediating role of Investment Recovery and Competitiveness. This paper also serves as an initiative to identify if the relationship between Investment Recovery and Firm Performance Measures is mediated by Competitiveness. Design/ Methodology/Approach: This study is based on survey Data collected from 272, ISO (14001) Certified Textile Firms Based in Lahore, Faisalabad, and Karachi which are involved in Spinning, Dyeing, Printing or Bleaching. A Theoretical model was developed incorporating the constructs representing Green Activities and Firm Performance Measures of a firm. The data was analyzed using Partial Least Square Structural Equation Modeling. Senior and Mid-level managers provided the data reflecting the degree to which their organizations deal with both internal and external stakeholders to improve the environmental sustainability of their supply chain. Findings: Of the 36 proposed Hypothesis, 20 are considered valid and significant. The statistics result reveal that GrSCM practices positively impact Environmental Performance followed by Economic and Operational Performance. Investment Recovery acts as a strong mediator between Intra organizational Green activities and performance outcomes. The relationship of Reverse Logistics influencing outcomes is significantly mediated by Competitiveness. The pressure originating from customers exert significant positive influence on the firm to adopt Green Practices consequently leading to higher outcomes. Research Contribution/Originality: Underpinning the Resource dependence theory and as a first wave of investigating the impact of Green Supply chain on performance outcomes in Pakistan, this study intends to make a prominent mark in the field of research. Investment and Competitiveness together are tested as a mediator for the first time in this arena. Managerial implications: Practitioner is provided with a framework for assessing the synergistic impact of GrSCM practices on performance. Upgradation of Accreditations and Audit Programs on regular basis are the need of the hour. Making the processes leaner with the sale of excess inventories and scrap helps the firm to work more efficiently and productively.

Keywords: economic performance, environmental performance, green supply chain management practices, operational performance, sustainability, a textile sector of Pakistan

Procedia PDF Downloads 206
4679 Glaucoma with Normal IOP, Is It True Normal Tension glaucoma or Something Else!

Authors: Sushma Tejwani, Shoruba Dinakaran, Kushal Kacha, K. Bhujang Shetty

Abstract:

Introduction and aim: It is not unusual to find patients with glaucomatous damage and normal intraocular pressure, and to label a patient as Normal tension glaucoma (NTG) majority of clinicians depend on office Intraocular pressures (IOP) recordings; hence, the concern is that whether we are missing the late night or early morning spikes in this group of patients. Also, ischemia to the optic nerve is one of the presumed causes of damage in these patients, however demonstrating the same has been a challenge. The aim of this study was to evaluate IOP variations and patterns in a series of patients with open angles, glaucomatous discs or fields but normal office IOP, and in addition to identify ischemic factors for true NTG patients. Materials & Methods: This was an observational cross- sectional study from a tertiary care centre. The patients that underwent full day DVT from Jan 2012 to April 2014 were studied. All patients underwent IOP measurement on Goldmann applanation tonometry every 3 hours for 24 hours along with a recording of the blood pressure (BP). Further patients with normal IOP throughout the 24- hour period were evaluated with a cardiologist for echocardiography and carotid Doppler. Results: There were 47 patients and a maximum number of patients studied was in the age group of 50-70 years. A biphasic IOP peak was noted for almost all the patients. Out of the 47 patients, 2 were excluded from analysis as they were on treatment.20 patients (42%) were diagnosed on DVT to have an IOP spike and were then diagnosed as open angle glaucoma and another 25 (55%) were diagnosed to have normal tension glaucoma and were subsequently advised a carotid Doppler and a cardiologists consult. Another interesting finding was that 9 patients had a nocturnal dip in their BP and 3 were found to have carotid artery stenosis. Conclusion: A continuous 24-hour monitoring of the IOP and BP is a very useful albeit mildly cumbersome tool which provides a wealth of information in cases of glaucoma presenting with normal office pressures. It is of great value in differentiating between normal tension glaucoma patients & open angle glaucoma patients. It also helps in timely diagnosis & possible intervention due to referral to a cardiologist in cases of carotid artery stenosis.

Keywords: carotid artery disease in NTG, diurnal variation of IOP, ischemia in glaucoma, normal tension glaucoma

Procedia PDF Downloads 269
4678 Climate Change: A Critical Analysis on the Relationship between Science and Policy

Authors: Paraskevi Liosatou

Abstract:

Climate change is considered to be of global concern being amplified by the fact that by its nature, cannot be spatially limited. This fact makes necessary the intergovernmental decision-making procedures. In the intergovernmental level, the institutions such as the United Nations Framework Convention on Climate Change and the Intergovernmental Panel on Climate Change develop efforts, methods, and practices in order to plan and suggest climate mitigation and adaptation measures. These measures are based on specific scientific findings and methods making clear the strong connection between science and policy. In particular, these scientific recommendations offer a series of practices, methods, and choices mitigating the problem by aiming at the indirect mitigation of the causes and the factors amplifying climate change. Moreover, modern production and economic context do not take into consideration the social, political, environmental and spatial dimensions of the problem. This work studies the decision-making process working in international and European level. In this context, this work considers the policy tools that have been implemented by various intergovernmental organizations. The methodology followed is based mainly on the critical study of standards and process concerning the connections and cooperation between science and policy as well as considering the skeptic debates developed. The finding of this work focuses on the links between science and policy developed by the institutional and scientific mechanisms concerning climate change mitigation. It also analyses the dimensions and the factors of the science-policy framework; in this way, it points out the causes that maintain skepticism in current scientific circles.

Keywords: climate change, climate change mitigation, climate change skepticism, IPCC, skepticism

Procedia PDF Downloads 124
4677 Crop Losses, Produce Storage and Food Security, the Nexus: Attaining Sustainable Maize Production in Nigeria

Authors: Charles Iledun Oyewole, Harira Shuaib

Abstract:

While fulfilling the food security of an increasing population like Nigeria remains a major global concern, more than one-third of crop harvested is lost or wasted during harvesting or in postharvest operations. Reducing the harvest and postharvest losses, especially in developing countries, could be a sustainable solution to increase food availability, eliminate hunger and improve farmers’ livelihoods. Nigeria is one of the countries in sub-Saharan Africa with insufficient food production and high food import bill, which has had debilitating effects on the country’s economy. One of the goals of Nigeria’s agricultural development policy is to ensure that, the nation produces enough food and be less dependent on importation so as to ensure adequate and affordable food for all. Maize could fill the food gap in Nigeria’s effort to beat hunger and food insecurity. Maize is the most important cereal after rice and its production contributes immensely to food availability on the tables of many Nigerians. Maize grains constitute primary source of food for large percentage of the Nigerian populace, thus a considerable waste of this valuable food pre and post-harvest constitutes such a major agricultural bottleneck; that the reduction of pre and post-harvest losses is now a common food security strategy. In surveys conducted, as much as 60% maize outputs can be lost on the field and during the storage stage due to technical inefficiency. Field losses due to rodent damage alone can account for between 10% - 60% grain losses depending on the location. While the use of scientific storage methods can reduce losses below 2% in storage, timely harvesting of crop can check losses on the fields resulting from rodent damage or pest infestation. A push for increased crop production must be complemented by available and affordable post-harvest technologies that will reduce losses on farmers’ fields as well as in storage.

Keywords: government policy, maize, population increase, storage, sustainable food production, yield, yield losses

Procedia PDF Downloads 125
4676 Effects of Continuous Training on Anthropometric Characteristics of Adolescents in Kano, Nigeria

Authors: Emmanuel S. Adeyanju

Abstract:

This study assessed the effects of continuous training on anthropometric characteristics of adolescents in Kano, Nigeria. The anthropometric measures of per cent body fat (%BF), body mass index (BMI), conicity index (CI) and waist-to-hip ratio (WHR) were selected because of their roles in increased adiposity and favourable cardiovascular disease (CVD) factor profiles in children and adolescence. The international standards and procedures were followed in all the measurements. A total of thirty (30) subjects (M=15; F=15), selected at random, were divided into two groups; one training (M=10; F=10) and the other control (M=5; F=5). Both groups were tested before training, at six (6) and 12 weeks in all the listed variables. The training group had 12 weeks continuous training which involved running round the standard 400 m track of the college following standard procedures; while the control group did not. The findings revealed significant sex-specific reductions in %BF (F=610.482 ˂ 0.05), BMI (F=73.860 ˂ 0.05), WHR (F=49.756 ˂ 0.05); however, no significant training effect on CI (F=1.855 ˃ 0.05) and WHR (F=1.956 ˃ 0.05) was found. Greater modifications found in females than in males (except in CI and WHR) due to training were probably related to their initial level of fitness and enzymatic modifications at subcellular level during training. The result also revealed significant relationship between the modifications in %BF, BMI and WHR but failed to establish any between CI and other adiposity measures. Thus, to avert the consequences of obesity and overweight, the declining fitness level of adolescents should be checked by ensuring they engaged in regular moderate-to-vigorous physical activity (MVPA) programmes. Such a childhood habit of exercise developed early in life will have a carry-over value into adult life and improve the quality of adult population.

Keywords: adiposity, anthropometry, conicity, continuous training

Procedia PDF Downloads 439
4675 Comparative Parametric Analysis on the Dynamic Response of Fibre Composite Beams with Debonding

Authors: Indunil Jayatilake, Warna Karunasena

Abstract:

Fiber Reinforced Polymer (FRP) composites enjoy an array of applications ranging from aerospace, marine and military to automobile, recreational and civil industry due to their outstanding properties. A structural glass fiber reinforced polymer (GFRP) composite sandwich panel made from E-glass fiber skin and a modified phenolic core has been manufactured in Australia for civil engineering applications. One of the major mechanisms of damage in FRP composites is skin-core debonding. The presence of debonding is of great concern not only because it severely affects the strength but also it modifies the dynamic characteristics of the structure, including natural frequency and vibration modes. This paper deals with the investigation of the dynamic characteristics of a GFRP beam with single and multiple debonding by finite element based numerical simulations and analyses using the STRAND7 finite element (FE) software package. Three-dimensional computer models have been developed and numerical simulations were done to assess the dynamic behavior. The FE model developed has been validated with published experimental, analytical and numerical results for fully bonded as well as debonded beams. A comparative analysis is carried out based on a comprehensive parametric investigation. It is observed that the reduction in natural frequency is more affected by single debonding than the equally sized multiple debonding regions located symmetrically to the single debonding position. Thus it is revealed that a large single debonding area leads to more damage in terms of natural frequency reduction than isolated small debonding zones of equivalent area, appearing in the GFRP beam. Furthermore, the extents of natural frequency shifts seem mode-dependent and do not seem to have a monotonous trend of increasing with the mode numbers.

Keywords: debonding, dynamic response, finite element modelling, novel FRP beams

Procedia PDF Downloads 105
4674 90-Day Strength Training Intervention Decreases Incidence of Sarcopenia: A Pre- and Posttest Pilot Study of Older Adults in a Skilled Nursing Facility

Authors: Donna-Marie Phyllis Lanton

Abstract:

Sarcopenia is a well-known geriatric syndrome characterized by the progressive and generalized loss of muscle quantity or quality. The incidence of sarcopenia increases with age and is associated with adverse outcomes such as the increased risk of falls, cognitive impairment, loss of independence, diminished quality of life, increased health costs, need for care in a skilled nursing facility, and increased mortality. Physical activity, including resistance training, is the most prevalent recommendation for treating and preventing sarcopenia. Residents (N = 23) of a skilled nursing facility in East Orlando, Florida, participated in a 90-day strength training program designed using the PARIHS framework to improve measures of muscle mass, muscle strength, physical performance, and quality of life. Residents engaged in both resistance and balance exercises for 1 hour two times a week. Baseline data were collected and compared to data at Days 30, 60, and 90. T tests indicated significant gains on all measures from baseline to 90 days: muscle mass increased by 1.2 (t[22] = 2.85, p = .009), grip strength increased by 4.02 (t[22] = 8.15, p < .001), balance increased by 2.13 (t[22] = 18.64, p < .001), gait speed increased by 1.83 (t[22] = 17.84, p < .001), chair speed increased 1.87 (t[22] = 16.36, p < .001), and quality of life score increased by 17.5 (t[22] = 19.26, p < .001). For residents with sarcopenia in skilled nursing facilities, a 90-day strength training program with resistance and balance exercises may provide an option for decreasing the incidence of sarcopenia among that population

Keywords: muscle mass, muscle strength, older adults, PARIHS framework

Procedia PDF Downloads 76
4673 Tuning of Fixed Wing Micro Aerial Vehicles Using Tethered Setup

Authors: Shoeb Ahmed Adeel, Vivek Paul, K. Prajwal, Michael Fenelon

Abstract:

Techniques have been used to tether and stabilize a multi-rotor MAV but carrying out the same process to a fixed wing MAV is a novel method which can be utilized in order to reduce damage occurring to the fixed wing MAVs while conducting flight test trials and PID tuning. A few sensors and on board controller is required to carry out this experiment in horizontal and vertical plane of the vehicle. Here we will be discussing issues such as sensitivity of the air vehicle, endurance and external load of the string acting on the vehicle.

Keywords: MAV, PID tuning, tethered flight, UAV

Procedia PDF Downloads 621
4672 Spatial and Temporal Analysis of Forest Cover Change with Special Reference to Anthropogenic Activities in Kullu Valley, North-Western Indian Himalayan Region

Authors: Krisala Joshi, Sayanta Ghosh, Renu Lata, Jagdish C. Kuniyal

Abstract:

Throughout the world, monitoring and estimating the changing pattern of forests across diverse landscapes through remote sensing is instrumental in understanding the interactions of human activities and the ecological environment with the changing climate. Forest change detection using satellite imageries has emerged as an important means to gather information on a regional scale. Kullu valley in Himachal Pradesh, India is situated in a transitional zone between the lesser and the greater Himalayas. Thus, it presents a typical rugged mountainous terrain with moderate to high altitude which varies from 1200 meters to over 6000 meters. Due to changes in agricultural cropping patterns, urbanization, industrialization, hydropower generation, climate change, tourism, and anthropogenic forest fire, it has undergone a tremendous transformation in forest cover in the past three decades. The loss and degradation of forest cover results in soil erosion, loss of biodiversity including damage to wildlife habitats, and degradation of watershed areas, and deterioration of the overall quality of nature and life. The supervised classification of LANDSAT satellite data was performed to assess the changes in forest cover in Kullu valley over the years 2000 to 2020. Normalized Burn Ratio (NBR) was calculated to discriminate between burned and unburned areas of the forest. Our study reveals that in Kullu valley, the increasing number of forest fire incidents specifically, those due to anthropogenic activities has been on a rise, each subsequent year. The main objective of the present study is, therefore, to estimate the change in the forest cover of Kullu valley and to address the various social aspects responsible for the anthropogenic forest fires. Also, to assess its impact on the significant changes in the regional climatic factors, specifically, temperature, humidity, and precipitation over three decades, with the help of satellite imageries and ground data. The main outcome of the paper, we believe, will be helpful for the administration for making a quantitative assessment of the forest cover area changes due to anthropogenic activities and devising long-term measures for creating awareness among the local people of the area.

Keywords: Anthropogenic Activities, Forest Change Detection, Normalized Burn Ratio (NBR), Supervised Classification

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4671 Philippine National Police Strategies in the Implementation of 'Peace and Order Agenda for Transformation and Upholding of the Rule-Of-Law' Plan 2030

Authors: Ruby A. L. Espineli

Abstract:

The study assessed the Philippine National Police strategies in the implementation of ‘Peace and Order Agenda for Transformation and Upholding of the Rule-of-Law’ P.A.T.R.O.L Plan 2030. Its operational roadmap presents four perspectives which include resource management, learning and growth, process excellence; and community. Focused group discussion, observation, and distribution of survey questionnaire to selected PNP officers and community members were done to identify and describe the implementation, problems encountered and measures to address the problems of the PNP P.A.T.R.O.L Plan 2030. In resource management, PNP allocates most sufficient funds in providing service firearms, patrol vehicle, and internet connections. In terms of learning and growth, the attitude of PNP officers is relatively higher than their knowledge and skills. Moreover, in terms of process excellence, the PNP use several crime preventions and crime solution strategies to deliver an immediate response to calls of the community. As regards, community perspective, PNP takes effort in establishing partnership with community. It is also interesting to note that PNP officers and community were both undecided on the existence of problems encountered in the implementation of P.A.T.R.O.L Plan 2030. But, they had proactive behavior as they agreed on all the specified measures to address the problems encountered in implementation of PNP P.A.T.R.O.L. Plan 2030. A strategic framework, based on the findings was formulated in this study that could improve and entrench the harmonious working relationship between the PNP and stakeholders in the enhancement of the implementation of PNP P.A.T.R.O.L. Plan 2030.

Keywords: community perspectives, learning and growth, process excellence, resource management

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4670 Morphology Analysis of Apple-Carrot Juice Treated by Manothermosonication (MTS) and High Temperature Short Time (HTST) Processes

Authors: Ozan Kahraman, Hao Feng

Abstract:

Manothermosonication (MTS), which consists of the simultaneous application of heat and ultrasound under moderate pressure (100-700 kPa), is one of the technologies which destroy microorganisms and inactivates enzymes. Transmission electron microscopy (TEM) is a microscopy technique in which a beam of electrons is transmitted through an ultra-thin specimen, interacting with the specimen as it passes through it. The environmental scanning electron microscope or ESEM is a scanning electron microscope (SEM) that allows for the option of collecting electron micrographs of specimens that are "wet," uncoated. These microscopy techniques allow us to observe the processing effects on the samples. This study was conducted to investigate the effects of MTS and HTST treatments on the morphology of apple-carrot juices by using TEM and ESEM microscopy. Apple-carrot juices treated with HTST (72 0C, 15 s), MTS 50 °C (60 s, 200 kPa), and MTS 60 °C (30 s, 200 kPa) were observed in both ESEM and TEM microscopy. For TEM analysis, a drop of the solution dispersed in fixative solution was put onto a Parafilm ® sheet. The copper coated side of the TEM sample holder grid was gently laid on top of the droplet and incubated for 15 min. A drop of a 7% uranyl acetate solution was added and held for 2 min. The grid was then removed from the droplet and allowed to dry at room temperature and presented into the TEM. For ESEM analysis, a critical point drying of the filters was performed using a critical point dryer (CPD) (Samdri PVT- 3D, Tousimis Research Corp., Rockville, MD, USA). After the CPD, each filter was mounted onto a stub and coated with gold/palladium with a sputter coater (Desk II TSC Denton Vacuum, Moorestown, NJ, USA). E.Coli O157:H7 cells on the filters were observed with an ESEM (Philips XL30 ESEM-FEG, FEI Co., Eindhoven, The Netherland). ESEM (Environmental Scanning Electron Microscopy) and TEM (Transmission Electron Microscopy) images showed extensive damage for the samples treated with MTS at 50 and 60 °C such as ruptured cells and breakage on cell membranes. The damage was increasing with increasing exposure time.

Keywords: MTS, HTST, ESEM, TEM, E.COLI O157:H7

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4669 Living with a Partner with Depression: The Role of Dispositional Empathy in Psychological Resilience

Authors: Elizabeth O'Brien, Raegan Murphy

Abstract:

Research suggests that high levels of empathy in individuals with partners with mental health difficulties can lead to improved outcomes for their partner while compromising their own mental health. Specifically, it is proposed that the affective dimension of empathy diminishes resilience to the distress of a partner, whereas cognitive empathy (CE) enhances it. The relationship between different empathy dimensions and psychological resilience measures has not been investigated in partners of people with depression. Psychological inflexibility (PI) is a construct that can be understood as distress intolerance and is suggested to be an important feature of psychological resilience. The current study, therefore, aimed to investigate the differential role of dispositional empathy dimensions in PI for people living with a partner with depression. A cross-sectional design was employed in which 148 participants living with a partner with depression and 45 participants for a comparison sample were recruited using online platforms. Participants completed online surveys with measures relating to demographics, empathy, and PI. Scores were compared between the study and comparison samples. The study sample scored significantly lower for CE and affective empathy (AE) and significantly higher for PI than the comparison sample. Exploratory and regression analyses were run to examine associations between variables within the study sample. Analyses revealed that CE predicted the resilience outcome whilst AE did not. These results suggest that interventions for partners of people with depression that bolster the CE dimension alone may improve mental health outcomes for both members of the couple relationship.

Keywords: affective empathy, cognitive empathy, depression, partners, psychological inflexibility

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4668 Profiling of the Cell-Cycle Related Genes in Response to Efavirenz, a Non-Nucleoside Reverse Transcriptase Inhibitor in Human Lung Cancer

Authors: Rahaba Marima, Clement Penny

Abstract:

The Health-related quality of life (HRQoL) for HIV positive patients has improved since the introduction of the highly active antiretroviral treatment (HAART). However, in the present HAART era, HIV co-morbidities such as lung cancer, a non-AIDS (NAIDS) defining cancer have been documented to be on the rise. Under normal physiological conditions, cells grow, repair and proliferate through the cell-cycle as cellular homeostasis is important in the maintenance and proper regulation of tissues and organs. Contrarily, the deregulation of the cell-cycle is a hallmark of cancer, including lung cancer. The association between lung cancer and the use of HAART components such as Efavirenz (EFV) is poorly understood. This study aimed at elucidating the effects of EFV on the cell-cycle genes’ expression in lung cancer. For this purpose, the human cell-cycle gene array composed of 84 genes was evaluated on both normal lung fibroblasts (MRC-5) cells and adenocarcinoma (A549) lung cells, in response to 13µM EFV or 0.01% vehicle. The ±2 up or down fold change was used as a basis of target selection, with p < 0.05. Additionally, RT-qPCR was done to validate the gene array results. Next, In-silico bio-informatics tools, Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Reactome, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Ingenuity Pathway Analysis (IPA) were used for gene/gene interaction studies as well as to map the molecular and biological pathways influenced by the identified targets. Interestingly, the DNA damage response (DDR) pathway genes such as p53, Ataxia telangiectasia mutated and Rad3 related (ATR), Growth arrest and DNA damage inducible alpha (GADD45A), HUS1 checkpoint homolog (HUS1) and Role of radiation (RAD) genes were shown to be upregulated following EFV treatment, as revealed by STRING analysis. Additionally, functional enrichment analysis by the KEGG pathway revealed that most of the differentially expressed gene targets function at the cell-cycle checkpoint such as p21, Aurora kinase B (AURKB) and Mitotic Arrest Deficient-Like 2 (MAD2L2). Core analysis by IPA revealed that p53 downstream targets such as survivin, Bcl2, and cyclin/cyclin dependent kinases (CDKs) complexes are down-regulated, following exposure to EFV. Furthermore, Reactome analysis showed a significant increase in cellular response to stress genes, DNA repair genes, and apoptosis genes, as observed in both normal and cancerous cells. These findings implicate the genotoxic effects of EFV on lung cells, provoking the DDR pathway. Notably, the constitutive expression of this pathway (DDR) often leads to uncontrolled cell proliferation and eventually tumourigenesis, which could be the attribute of HAART components’ (such as EFV) effect on human cancers. Targeting the cell-cycle and its regulation holds a promising therapeutic intervention to the potential HAART associated carcinogenesis, particularly lung cancer.

Keywords: cell-cycle, DNA damage response, Efavirenz, lung cancer

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4667 Dynamic Analysis of Turbine Foundation

Authors: Mogens Saberi

Abstract:

This paper presents different design approaches for the design of turbine foundations. In the design process, several unknown factors must be considered such as the soil stiffness at the site. The main static and dynamic loads are presented and the results of a dynamic simulation are presented for a turbine foundation that is currently being built. A turbine foundation is an important part of a power plant since a non-optimal behavior of the foundation can damage the turbine itself and thereby stop the power production with large consequences.

Keywords: dynamic turbine design, harmonic response analysis, practical turbine design experience, concrete foundation

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4666 Understanding the Fundamental Driver of Semiconductor Radiation Tolerance with Experiment and Theory

Authors: Julie V. Logan, Preston T. Webster, Kevin B. Woller, Christian P. Morath, Michael P. Short

Abstract:

Semiconductors, as the base of critical electronic systems, are exposed to damaging radiation while operating in space, nuclear reactors, and particle accelerator environments. What innate property allows some semiconductors to sustain little damage while others accumulate defects rapidly with dose is, at present, poorly understood. This limits the extent to which radiation tolerance can be implemented as a design criterion. To address this problem of determining the driver of semiconductor radiation tolerance, the first step is to generate a dataset of the relative radiation tolerance of a large range of semiconductors (exposed to the same radiation damage and characterized in the same way). To accomplish this, Rutherford backscatter channeling experiments are used to compare the displaced lattice atom buildup in InAs, InP, GaP, GaN, ZnO, MgO, and Si as a function of step-wise alpha particle dose. With this experimental information on radiation-induced incorporation of interstitial defects in hand, hybrid density functional theory electron densities (and their derived quantities) are calculated, and their gradient and Laplacian are evaluated to obtain key fundamental information about the interactions in each material. It is shown that simple, undifferentiated values (which are typically used to describe bond strength) are insufficient to predict radiation tolerance. Instead, the curvature of the electron density at bond critical points provides a measure of radiation tolerance consistent with the experimental results obtained. This curvature and associated forces surrounding bond critical points disfavors localization of displaced lattice atoms at these points, favoring their diffusion toward perfect lattice positions. With this criterion to predict radiation tolerance, simple density functional theory simulations can be conducted on potential new materials to gain insight into how they may operate in demanding high radiation environments.

Keywords: density functional theory, GaN, GaP, InAs, InP, MgO, radiation tolerance, rutherford backscatter channeling

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4665 Development of a Practical Screening Measure for the Prediction of Low Birth Weight and Neonatal Mortality in Upper Egypt

Authors: Prof. Ammal Mokhtar Metwally, Samia M. Sami, Nihad A. Ibrahim, Fatma A. Shaaban, Iman I. Salama

Abstract:

Objectives: Reducing neonatal mortality by 2030 is still a challenging goal in developing countries. low birth weight (LBW) is a significant contributor to this, especially where weighing newborns is not possible routinely. The present study aimed to determine a simple, easy, reliable anthropometric measure(s) that can predict LBW) and neonatal mortality. Methods: A prospective cohort study of 570 babies born in districts of El Menia governorate, Egypt (where most deliveries occurred at home) was examined at birth. Newborn weight, length, head, chest, mid-arm, and thigh circumferences were measured. Follow up of the examined neonates took place during their first four weeks of life to report any mortalities. The most predictable anthropometric measures were determined using the statistical package of SPSS, and multiple Logistic regression analysis was performed.: Results: Head and chest circumferences with cut-off points < 33 cm and ≤ 31.5 cm, respectively, were the significant predictors for LBW. They carried the best combination of having the highest sensitivity (89.8 % & 86.4 %) and least false negative predictive value (1.4 % & 1.7 %). Chest circumference with a cut-off point ≤ 31.5 cm was the significant predictor for neonatal mortality with 83.3 % sensitivity and 0.43 % false negative predictive value. Conclusion: Using chest circumference with a cut-off point ≤ 31.5 cm is recommended as a single simple anthropometric measurement for the prediction of both LBW and neonatal mortality. The predicted measure could act as a substitute for weighting newborns in communities where scales to weigh them are not routinely available.

Keywords: low birth weight, neonatal mortality, anthropometric measures, practical screening

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4664 Understanding Tourism Innovation through Fuzzy Measures

Authors: Marcella De Filippo, Delio Colangelo, Luca Farnia

Abstract:

In recent decades, the hyper-competition of tourism scenario has implicated the maturity of many businesses, attributing a central role to innovative processes and their dissemination in the economy of company management. At the same time, it has defined the need for monitoring the application of innovations, in order to govern and improve the performance of companies and destinations. The study aims to analyze and define the innovation in the tourism sector. The research actions have concerned, on the one hand, some in-depth interviews with experts, identifying innovation in terms of process and product, digitalization, sustainability policies and, on the other hand, to evaluate the interaction between these factors, in terms of substitutability and complementarity in management scenarios, in order to identify which one is essential to be competitive in the global scenario. Fuzzy measures and Choquet integral were used to elicit Experts’ preferences. This method allows not only to evaluate the relative importance of each pillar, but also and more interestingly, the level of interaction, ranging from complementarity to substitutability, between pairs of factors. The results of the survey are the following: in terms of Shapley values, Experts assert that Innovation is the most important factor (32.32), followed by digitalization (31.86), Network (20.57) and Sustainability (15.25). In terms of Interaction indices, given the low degree of consensus among experts, the interaction between couples of criteria on average could be ignored; however, it is worth to note that the factors innovations and digitalization are those in which experts express the highest degree of interaction. However for some of them, these factors have a moderate level of complementarity (with a pick of 57.14), and others consider them moderately substitutes (with a pick of -39.58). Another example, although outlier is the interaction between network and digitalization, in which an expert consider them markedly substitutes (-77.08).

Keywords: innovation, business model, tourism, fuzzy

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4663 The Use of Five Times Sit-To-Stand Test in Ambulatory People with Spinal Cord Injury When Tested with or without Hands

Authors: Lalita Khuna, Sugalya Amatachaya, Pipatana Amatachaya, Thiwabhorn Thaweewannakij, Pattra Wattanapan

Abstract:

The five times sit-to-stand test (FTSST) has been widely used to quantify lower extremity motor strength (LEMS), dynamic balance ability, and risk of falls in many individuals. Recently, it has been used in ambulatory patients with spinal cord injury (SCI) but variously using with or without hands according to patients’ ability. This difference might affect the validity of the test in these individuals. Thus, this study assessed the concurrent validity of the FTSST in ambulatory individuals with SCI, separately for those who could complete the test with or without hands using LEMS and standard functional measures as gold standards. Moreover, the data of the tests from those who completed the FTSST with and without hands were compared. A total of 56 ambulatory participants with SCI who could complete sit-to-stand with or without hands were assessed for the time to complete the FTSST according to their ability. Then they were assessed for their LEMS scores and functional abilities, including the 10-meter walk test (10MWT), the walking index for spinal cord injury II (WISCI II), the timed up and go test (TUGT), and the 6-minute walk test (6MWT). The Mann-Whitney U test was used to compare the different findings between the participants who performed the FTSST with and without hands. The Spearman rank correlation coefficient (ρ) was applied to analyze the levels of correlation between the FTSST and standard tests (LEMS scores and functional measures). There were significant differences in the data between the participants who performed the test with and without hands (p < 0.01). The time to complete the FTSST of the participants who performed the test without hands showed moderate to strong correlation with total LEMS scores and all functional measures (ρ = -0.71 to 0.69, p < 0.001). On the contrary, the FTSST data of those who performed the test with hands were significantly correlated only with the 10MWT, TUGT, and 6MWT (ρ = -0.47 to 0.57, p < 0.01). The present findings confirm the concurrent validity of the FTSST when performed without hands for LEMS and functional mobility necessary for the ability of independence and safety of ambulatory individuals with SCI. However, the test using hands distort the ability of the outcomes to reflect LEMS and WISCI II that reflect lower limb functions. By contrast, the 10MWT, TUGT, and 6MWT allowed upper limb contribution in the tests. Therefore, outcomes of these tests showed a significant correlation to the outcomes of FTSST when assessed using hands. Consequently, the use of FTSST with or without hands needs to consider the clinical application of the outcomes, i.e., to reflect lower limb functions or mobility of the patients.

Keywords: mobility, lower limb muscle strength, clinical test, rehabilitation

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4662 Microstructure Dependent Fatigue Crack Growth in Aluminum Alloy

Authors: M. S. Nandana, K. Udaya Bhat, C. M. Manjunatha

Abstract:

In this study aluminum alloy 7010 was subjected to three different ageing treatments i.e., peak ageing (T6), over-ageing (T7451) and retrogression and re ageing (RRA) to study the influence of precipitate microstructure on the fatigue crack growth rate behavior. The microstructural modification was studied by using transmission electron microscope (TEM) to examine the change in the size and morphology of precipitates in the matrix and on the grain boundaries. The standard compact tension (CT) specimens were fabricated and tested under constant amplitude fatigue crack growth tests to evaluate the influence of heat treatment on the fatigue crack growth rate properties. The tests were performed in a computer-controlled servo-hydraulic test machine applying a load ratio, R = 0.1 at a loading frequency of 10 Hz as per ASTM E647. The fatigue crack growth was measured by adopting compliance technique using a CMOD gauge attached to the CT specimen. The average size of the matrix precipitates were found to be of 16-20 nm in T7451, 5-6 nm in RRA and 2-3 nm in T6 conditions respectively. The grain boundary precipitate which was continuous in T6, was disintegrated in RRA and T7451 condition. The PFZ width was lower in RRA compared to T7451 condition. The crack growth rate was higher in T7451 and lowest in RRA treated alloy. The RRA treated alloy also exhibits an increase in threshold stress intensity factor range (∆Kₜₕ). The ∆Kₜₕ measured was 11.1, 10.3 and 5.7 MPam¹/² in RRA, T6 and T7451 alloys respectively. The fatigue crack growth rate in RRA treated alloy was nearly 2-3 times lower than that in T6 and was one order lower than that observed in T7451 condition. The surface roughness of RRA treated alloy was more pronounced when compared to the other conditions. The reduction in fatigue crack growth rate in RRA alloy was majorly due to the increase in roughness and partially due to increase in spacing between the matrix precipitates. The reduction in crack growth rate and increase in threshold stress intensity range is expected to benefit the damage tolerant capability of aircraft structural components under service loads.

Keywords: damage tolerance, fatigue, heat treatment, PFZ, RRA

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4661 Climate Change Based Frontier Research in Landscape Architecture

Authors: Xiaoyan Wang, Zhongde Wang

Abstract:

The issue of climate change, which originated in the middle of the twentieth century, has become a focus of international political, academic, and non-governmental organizations and public attention. In order to address the problems caused by climate change, the Chinese government has proposed a dual-carbon target and taken some national measures, such as ecological priority and green low-carbon development. These goals and measures are highly aligned with the values of the landscape architecture industry. This is an opportunity for the architectural discipline and the landscape architecture industry, so it is very necessary to summarize and analyze the hotspots related to climate change in the field of building science in China, which can assist the landscape architecture industry and related organizations in formulating more rational professional goals and taking actions that contribute to the betterment of societal, environmental development. Through the study, it is found as follows: firstly, after 20 years of rapid development, the research on climate change in the major architectural disciplines has shown a trend of diversification of research perspectives, interdisciplinary cross-cutting, and broadening of content; secondly, the research contents of landscape architecture focuses on the strategies to adapt to climate change, such as selection of urban tree species, the urban green infrastructure space layout, and the resilient city. Finally, in the future, climate change-based landscape architecture research will make the content system more diversified, but at the same time, it is still necessary to further deepen the research on quantitative methodology and construct scale systematic planning and design methods.

Keywords: climate change, landscape architecture, knowledge mapping, cites-pace

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4660 Investigation of Bird Impact on Tailplane

Authors: Reza Hedayati, Meysam Jahanbakhshi

Abstract:

The typical airplane stabilizer structures consist of two main similar segments (outer and inner parts), one of them a little larger than the other. In this study, bird impact on four different spots of the stabilizer structure: (a) between two ribs of smaller segment, (b) between two ribs of larger segment, (c) on the rib connecting the two segments, and (d) on a middle rib of the smaller segment, is investigated and their results are compared by means of energy absorption, displacement, and bird’s mass diagrams as well as visible damage induced on the stabilizer structure.

Keywords: airplane, bird strike, LS-DYNA, stabilizer

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4659 Air Dispersion Model for Prediction Fugitive Landfill Gaseous Emission Impact in Ambient Atmosphere

Authors: Moustafa Osman Mohammed

Abstract:

This paper will explore formation of HCl aerosol at atmospheric boundary layers and encourages the uptake of environmental modeling systems (EMSs) as a practice evaluation of gaseous emissions (“framework measures”) from small and medium-sized enterprises (SMEs). The conceptual model predicts greenhouse gas emissions to ecological points beyond landfill site operations. It focuses on incorporation traditional knowledge into baseline information for both measurement data and the mathematical results, regarding parameters influence model variable inputs. The paper has simplified parameters of aerosol processes based on the more complex aerosol process computations. The simple model can be implemented to both Gaussian and Eulerian rural dispersion models. Aerosol processes considered in this study were (i) the coagulation of particles, (ii) the condensation and evaporation of organic vapors, and (iii) dry deposition. The chemical transformation of gas-phase compounds is taken into account photochemical formulation with exposure effects according to HCl concentrations as starting point of risk assessment. The discussion set out distinctly aspect of sustainability in reflection inputs, outputs, and modes of impact on the environment. Thereby, models incorporate abiotic and biotic species to broaden the scope of integration for both quantification impact and assessment risks. The later environmental obligations suggest either a recommendation or a decision of what is a legislative should be achieved for mitigation measures of landfill gas (LFG) ultimately.

Keywords: air pollution, landfill emission, environmental management, monitoring/methods and impact assessment

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4658 Involvement of Nrf2 in Kolaviron-Mediated Attenuation of Behavioural Incompetence and Neurodegeneration in a Murine Model of Parkinson's Disease

Authors: Yusuf E. Mustapha, Inioluwa A Akindoyeni, Oluwatoyin G. Ezekiel, Ifeoluwa O. Awogbindin, Ebenezer O. Farombi

Abstract:

Background: Parkinson's disease (PD) is the most prevalent motor disorder. Available therapies are palliative with no effect on disease progression. Kolaviron (KV), a natural anti-inflammatory and antioxidant agent, has been reported to possess neuroprotective effects in Parkinsonian flies and rats. Objective: The present study investigates the neuroprotective effect of KV, focusing on the DJ1/Nrf2 signaling pathway. Methodology: All-trans retinoic acid (ATRA, 10 mg/kg, i.p.) was used to inhibit Nrf2. Murine model of PD was established with four doses of MPTP (20 mg/kg i.p.) at 2 hours interval. MPTP mice were pre-treated with either KV (200 mg/kg/day p.o), ATRA, or both conditions for seven days before PD induction. Motor behaviour was evaluated, and markers of oxidative stress/damage and its regulators were assessed with immunofluorescence and ELISA techniques. Results: MPTP-treated mice covered less distance with reduced numbers of anticlockwise rotations, heightened freezing, and prolonged immobility when compared to control. However, KV significantly attenuated these deficits. Pretreatment of MPTP mice with KV upregulated Nrf2 expression beyond MPTP level with a remarkable reduction in Keap1 expression and marked elevation of DJ-1 level, whereas co-administration with ATRA abrogated these effects. KV treatment restored MPTP-mediated depletion of endogenous antioxidant, striatal oxidative stress, oxidative damage, and inhibition of acetylcholinesterase activity. However, ATRA treatment potentiated acetylcholinesterase inhibition and attenuated the protective effect of KV on the level of nitric oxide and activities of catalase and superoxide dismutase. Conclusion: Kolaviron protects Parkinsonian mice by stabilizing and activating the Nrf2 signaling pathway. Thus, kolaviron can be explored as a pharmacological lead in PD management.

Keywords: Garcinia kola, Kolaviron, Parkinson Disease, Nrf2, behavioral incompetence, neurodegeneration

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4657 Targeting Mre11 Nuclease Overcomes Platinum Resistance and Induces Synthetic Lethality in Platinum Sensitive XRCC1 Deficient Epithelial Ovarian Cancers

Authors: Adel Alblihy, Reem Ali, Mashael Algethami, Ahmed Shoqafi, Michael S. Toss, Juliette Brownlie, Natalie J. Tatum, Ian Hickson, Paloma Ordonez Moran, Anna Grabowska, Jennie N. Jeyapalan, Nigel P. Mongan, Emad A. Rakha, Srinivasan Madhusudan

Abstract:

Platinum resistance is a clinical challenge in ovarian cancer. Platinating agents induce DNA damage which activate Mre11 nuclease directed DNA damage signalling and response (DDR). Upregulation of DDR may promote chemotherapy resistance. Here we have comprehensively evaluated Mre11 in epithelial ovarian cancers. In clinical cohort that received platinum- based chemotherapy (n=331), Mre11 protein overexpression was associated with aggressive phenotype and poor progression free survival (PFS) (p=0.002). In the ovarian cancer genome atlas (TCGA) cohort (n=498), Mre11 gene amplification was observed in a subset of serous tumours (5%) which correlated highly with Mre11 mRNA levels (p<0.0001). Altered Mre11 levels was linked with genome wide alterations that can influence platinum sensitivity. At the transcriptomic level (n=1259), Mre11 overexpression was associated with poor PFS (p=0.003). ROC analysis showed an area under the curve (AUC) of 0.642 for response to platinum-based chemotherapy. Pre-clinically, Mre11 depletion by gene knock down or blockade by small molecule inhibitor (Mirin) reversed platinum resistance in ovarian cancer cells and in 3D spheroid models. Importantly, Mre11 inhibition was synthetically lethal in platinum sensitive XRCC1 deficient ovarian cancer cells and 3D-spheroids. Selective cytotoxicity was associated with DNA double strand break (DSB) accumulation, S-phase cell cycle arrest and increased apoptosis. We conclude that pharmaceutical development of Mre11 inhibitors is a viable clinical strategy for platinum sensitization and synthetic lethality in ovarian cancer.

Keywords: MRE11; XRCC1, ovarian cancer, platinum sensitization, synthetic lethality

Procedia PDF Downloads 109