Search results for: cellular adaptation
Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 1749

Search results for: cellular adaptation

1479 Adjustment and Scale-Up Strategy of Pilot Liquid Fermentation Process of Azotobacter sp.

Authors: G. Quiroga-Cubides, A. Díaz, M. Gómez

Abstract:

The genus Azotobacter has been widely used as bio-fertilizer due to its significant effects on the stimulation and promotion of plant growth in various agricultural species of commercial interest. In order to obtain significantly viable cellular concentration, a scale-up strategy for a liquid fermentation process (SmF) with two strains of A. chroococcum (named Ac1 and Ac10) was validated and adjusted at laboratory and pilot scale. A batch fermentation process under previously defined conditions was carried out on a biorreactor Infors®, model Minifors of 3.5 L, which served as a baseline for this research. For the purpose of increasing process efficiency, the effect of the reduction of stirring speed was evaluated in combination with a fed-batch-type fermentation laboratory scale. To reproduce the efficiency parameters obtained, a scale-up strategy with geometric and fluid dynamic behavior similarities was evaluated. According to the analysis of variance, this scale-up strategy did not have significant effect on cellular concentration and in laboratory and pilot fermentations (Tukey, p > 0.05). Regarding air consumption, fermentation process at pilot scale showed a reduction of 23% versus the baseline. The percentage of reduction related to energy consumption reduction under laboratory and pilot scale conditions was 96.9% compared with baseline.

Keywords: Azotobacter chroococcum, scale-up, liquid fermentation, fed-batch process

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1478 Spatial Organization of Organelles in Living Cells: Insights from Mathematical Modelling

Authors: Congping Lin

Abstract:

Intracellular transport in fungi has a number of important roles in, e.g., filamentous fungal growth and cellular metabolism. Two basic mechanisms for intracellular transport are motor-driven trafficking along microtubules (MTs) and diffusion. Mathematical modelling has been actively developed to understand such intracellular transport and provide unique insight into cellular complexity. Based on live-cell imaging data in Ustilago hyphal cells, probabilistic models have been developed to study mechanism underlying spatial organization of molecular motors and organelles. In particular, anther mechanism - stochastic motility of dynein motors along MTs has been found to contribute to half of its accumulation at hyphal tip in order to support early endosome (EE) recycling. The EE trafficking not only facilitates the directed motion of peroxisomes but also enhances their diffusive motion. Considering the importance of spatial organization of early endosomes in supporting peroxisome movement, computational and experimental approaches have been combined to a whole-cell level. Results from this interdisciplinary study promise insights into requirements for other membrane trafficking systems (e.g., in neurons), but also may inform future 'synthetic biology' studies.

Keywords: intracellular transport, stochastic process, molecular motors, spatial organization

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1477 An Ultrasonic Signal Processing System for Tomographic Imaging of Reinforced Concrete Structures

Authors: Edwin Forero-Garcia, Jaime Vitola, Brayan Cardenas, Johan Casagua

Abstract:

This research article presents the integration of electronic and computer systems, which developed an ultrasonic signal processing system that performs the capture, adaptation, and analog-digital conversion to later carry out its processing and visualization. The capture and adaptation of the signal were carried out from the design and implementation of an analog electronic system distributed in stages: 1. Coupling of impedances; 2. Analog filter; 3. Signal amplifier. After the signal conditioning was carried out, the ultrasonic information was digitized using a digital microcontroller to carry out its respective processing. The digital processing of the signals was carried out in MATLAB software for the elaboration of A-Scan, B and D-Scan types of ultrasonic images. Then, advanced processing was performed using the SAFT technique to improve the resolution of the Scan-B-type images. Thus, the information from the ultrasonic images was displayed in a user interface developed in .Net with Visual Studio. For the validation of the system, ultrasonic signals were acquired, and in this way, the non-invasive inspection of the structures was carried out and thus able to identify the existing pathologies in them.

Keywords: acquisition, signal processing, ultrasound, SAFT, HMI

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1476 Integrated Decision Support for Energy/Water Planning in Zayandeh Rud River Basin in Iran

Authors: Safieh Javadinejad

Abstract:

In order to make well-informed decisions respecting long-term system planning, resource managers and policy creators necessitate to comprehend the interconnections among energy and water utilization and manufacture—and also the energy-water nexus. Planning and assessment issues contain the enhancement of strategies for declining the water and energy system’s vulnerabilities to climate alteration with also emissions of decreasing greenhouse gas. In order to deliver beneficial decision support for climate adjustment policy and planning, understanding the regionally-specific features of the energy-water nexus, and the history-future of the water and energy source systems serving is essential. It will be helpful for decision makers understand the nature of current water-energy system conditions and capacity for adaptation plans for future. This research shows an integrated hydrology/energy modeling platform which is able to extend water-energy examines based on a detailed illustration of local circumstances. The modeling links the Water Evaluation and Planning (WEAP) and the Long Range Energy Alternatives Planning (LEAP) system to create full picture of water-energy processes. This will allow water managers and policy-decision makers to simply understand links between energy system improvements and hydrological processing and realize how future climate change will effect on water-energy systems. The Zayandeh Rud river basin in Iran is selected as a case study to show the results and application of the analysis. This region is known as an area with large integration of both the electric power and water sectors. The linkages between water, energy and climate change and possible adaptation strategies are described along with early insights from applications of the integration modeling system.

Keywords: climate impacts, hydrology, water systems, adaptation planning, electricity, integrated modeling

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1475 Improving System Performance through User's Resource Access Patterns

Authors: K. C. Wong

Abstract:

This paper demonstrates a number of examples in the hope to shed some light on the possibility of designing future operating systems in a more adaptation-based manner. A modern operating system, we conceive, should possess the capability of 'learning' in such a way that it can dynamically adjust its services and behavior according to the current status of the environment in which it operates. In other words, a modern operating system should play a more proactive role during the session of providing system services to users. As such, a modern operating system is expected to create a computing environment, in which its users are provided with system services more matching their dynamically changing needs. The examples demonstrated in this paper show that user's resource access patterns 'learned' and determined during a session can be utilized to improve system performance and hence to provide users with a better and more effective computing environment. The paper also discusses how to use the frequency, the continuity, and the duration of resource accesses in a session to quantitatively measure and determine user's resource access patterns for the examples shown in the paper.

Keywords: adaptation-based systems, operating systems, resource access patterns, system performance

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1474 An Optimized Method for 3D Magnetic Navigation of Nanoparticles inside Human Arteries

Authors: Evangelos G. Karvelas, Christos Liosis, Andreas Theodorakakos, Theodoros E. Karakasidis

Abstract:

In the present work, a numerical method for the estimation of the appropriate gradient magnetic fields for optimum driving of the particles into the desired area inside the human body is presented. The proposed method combines Computational Fluid Dynamics (CFD), Discrete Element Method (DEM) and Covariance Matrix Adaptation (CMA) evolution strategy for the magnetic navigation of nanoparticles. It is based on an iteration procedure that intents to eliminate the deviation of the nanoparticles from a desired path. Hence, the gradient magnetic field is constantly adjusted in a suitable way so that the particles’ follow as close as possible to a desired trajectory. Using the proposed method, it is obvious that the diameter of particles is crucial parameter for an efficient navigation. In addition, increase of particles' diameter decreases their deviation from the desired path. Moreover, the navigation method can navigate nanoparticles into the desired areas with efficiency approximately 99%.

Keywords: computational fluid dynamics, CFD, covariance matrix adaptation evolution strategy, discrete element method, DEM, magnetic navigation, spherical particles

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1473 Spatial Distribution of Cellular Water in Pear Fruit: An Experimental Investigation

Authors: Md. Imran H. Khan, T. Farrell, M. A. Karim

Abstract:

Highly porous and hygroscopic characteristics of pear make it complex to understand the cellular level water distribution. In pear tissue, water is mainly distributed in three different spaces namely, intercellular water, intracellular water, and cell wall water. Understanding of these three types of water in pear tissue is crucial for predicting actual heat and mass transfer during drying. Therefore, the aim of the present study was to investigate the proportion of intercellular water, intracellular water, and cell wall water inside the pear tissue. During this study, Green Anjou Pear was taken for the investigation. The experiment was performed using 1H-NMR- T2 relaxometry. Various types of water component were calculated by using multi-component fits of the T2 relaxation curves. The experimental result showed that in pear tissue 78-82% water exist in intracellular space; 12-16% water in intercellular space and only 2-4% water exist in the cell wall space. The investigated results quantify different types of water in plant-based food tissue. The highest proportion of water exists in intracellular spaces. It was also investigated that the physical properties of pear and the proportion of the different types of water has a strong relationship. Cell wall water depends on the proportion of solid in the sample tissue whereas free water depends on the porosity of the material.

Keywords: intracellular water, intercellular water, cell wall water, physical property, pear

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1472 A Next Generation Multi-Scale Modeling Theatre for in silico Oncology

Authors: Safee Chaudhary, Mahnoor Naseer Gondal, Hira Anees Awan, Abdul Rehman, Ammar Arif, Risham Hussain, Huma Khawar, Zainab Arshad, Muhammad Faizyab Ali Chaudhary, Waleed Ahmed, Muhammad Umer Sultan, Bibi Amina, Salaar Khan, Muhammad Moaz Ahmad, Osama Shiraz Shah, Hadia Hameed, Muhammad Farooq Ahmad Butt, Muhammad Ahmad, Sameer Ahmed, Fayyaz Ahmed, Omer Ishaq, Waqar Nabi, Wim Vanderbauwhede, Bilal Wajid, Huma Shehwana, Muhammad Tariq, Amir Faisal

Abstract:

Cancer is a manifestation of multifactorial deregulations in biomolecular pathways. These deregulations arise from the complex multi-scale interplay between cellular and extracellular factors. Such multifactorial aberrations at gene, protein, and extracellular scales need to be investigated systematically towards decoding the underlying mechanisms and orchestrating therapeutic interventions for patient treatment. In this work, we propose ‘TISON’, a next-generation web-based multiscale modeling platform for clinical systems oncology. TISON’s unique modeling abstraction allows a seamless coupling of information from biomolecular networks, cell decision circuits, extra-cellular environments, and tissue geometries. The platform can undertake multiscale sensitivity analysis towards in silico biomarker identification and drug evaluation on cellular phenotypes in user-defined tissue geometries. Furthermore, integration of cancer expression databases such as The Cancer Genome Atlas (TCGA) and Human Proteome Atlas (HPA) facilitates in the development of personalized therapeutics. TISON is the next-evolution of multiscale cancer modeling and simulation platforms and provides a ‘zero-code’ model development, simulation, and analysis environment for application in clinical settings.

Keywords: systems oncology, cancer systems biology, cancer therapeutics, personalized therapeutics, cancer modelling

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1471 In Vivo Investigation of microRNA Expression and Function at the Mammalian Synapse by AGO-APP

Authors: Surbhi Surbhi, Andrea Erni, Gunter Meister, Harold Cremer, Christophe Beclin

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MicroRNAs (miRNAs) are short 20-23 nucleotide long non-coding RNAs; there are 2605 miRNA in humans and 1936 miRNA in mouse in total (miRBase). The nervous system expresses the most abundant miRNA and most diverse. MiRNAs play a role in many steps during neurogenesis, like cell proliferation, differentiation, neural patterning, axon pathfinding, etc. Moreover, in vitro studies suggested a role in the regulation of local translation at the synapse, thus controlling neuronal plasticity. However, due to the specific structure of miRNA molecules, an in-vivo confirmation of the general role of miRNAs in the control of neuronal plasticity is still pending. For example, their small size and their high level of sequence homology make difficult the analysis of their cellular and sub-cellular localization in-vivo by in-situ hybridization. Moreover, it was found that only 40% of the expressed miRNA molecules in a cell are included in RNA-Induced Silencing Complexes (RISC) and, therefore, involved in inhibitory interactions while the rest is silent. Definitively, the development of new tools is needed to have a better understanding of the cellular function of miRNAs, in particular their role in neuronal plasticity. Here we describe a new technique called in-vivo AGO-APP designed to investigate miRNA expression and function in-vivo. This technique is based on the expression of a small peptide derived from the human RISC-complex protein TNRC6B, called T6B, which binds all known Argonaute (Ago) proteins with high affinity allowing the efficient immunoprecipitation of AGO-bound miRNAs. We have generated two transgenic mouse lines conditionally expressing T6B either ubiquitously in the cell or targeted at the synapse. A comparison of the repertoire of miRNAs immuno-precipitated from mature neurons of both mouse lines will provide us with a list of miRNAs showing a specific activity at the synapse. The physiological role of these miRNAs will be subsequently addressed through gain and loss of function experiments.

Keywords: RNA-induced silencing complexes, TNRC6B, miRNA, argonaute, synapse, neuronal plasticity, neurogenesis

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1470 Governance Models of Higher Education Institutions

Authors: Zoran Barac, Maja Martinovic

Abstract:

Higher Education Institutions (HEIs) are a special kind of organization, with its unique purpose and combination of actors. From the societal point of view, they are central institutions in the society that are involved in the activities of education, research, and innovation. At the same time, their societal function derives complex relationships between involved actors, ranging from students, faculty and administration, business community and corporate partners, government agencies, to the general public. HEIs are also particularly interesting as objects of governance research because of their unique public purpose and combination of stakeholders. Furthermore, they are the special type of institutions from an organizational viewpoint. HEIs are often described as “loosely coupled systems” or “organized anarchies“ that implies the challenging nature of their governance models. Governance models of HEIs describe roles, constellations, and modes of interaction of the involved actors in the process of strategic direction and holistic control of institutions, taking into account each particular context. Many governance models of the HEIs are primarily based on the balance of power among the involved actors. Besides the actors’ power and influence, leadership style and environmental contingency could impact the governance model of an HEI. Analyzing them through the frameworks of institutional and contingency theories, HEI governance models originate as outcomes of their institutional and contingency adaptation. HEIs tend to fit to institutional context comprised of formal and informal institutional rules. By fitting to institutional context, HEIs are converging to each other in terms of their structures, policies, and practices. On the other hand, contingency framework implies that there is no governance model that is suitable for all situations. Consequently, the contingency approach begins with identifying contingency variables that might impact a particular governance model. In order to be effective, the governance model should fit to contingency variables. While the institutional context creates converging forces on HEI governance actors and approaches, contingency variables are the causes of divergence of actors’ behavior and governance models. Finally, an HEI governance model is a balanced adaptation of the HEIs to the institutional context and contingency variables. It also encompasses roles, constellations, and modes of interaction of involved actors influenced by institutional and contingency pressures. Actors’ adaptation to the institutional context brings benefits of legitimacy and resources. On the other hand, the adaptation of the actors’ to the contingency variables brings high performance and effectiveness. HEI governance models outlined and analyzed in this paper are collegial, bureaucratic, entrepreneurial, network, professional, political, anarchical, cybernetic, trustee, stakeholder, and amalgam models.

Keywords: governance, governance models, higher education institutions, institutional context, situational context

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1469 Small and Medium-Sized Enterprises in West African Semi-Arid Lands Facing Climate Change

Authors: Mamadou Diop, Florence Crick, Momadou Sow, Kate Elizabeth Gannon

Abstract:

Understanding SME leaders’ responses to climate is essential to cope with ongoing changes in temperature and rainfall. This study analyzes the response of SME leaders to the adverse effects of climate change in semi-arid lands (SAL) in Senegal. Based on surveys administrated to 161 SME leaders, this research shows that 91% of economic units are affected by climatic conditions, although 70% do not have a plan to deal with climate risks. Economic actors have striven to take measures to adapt. However, their efforts are limited by various obstacles accentuated by a lack of support from public authorities. In doing so, substantial political, institutional and financial efforts at national and local levels are needed to promote an enabling environment for economic actors to adapt. This will focus on information and training about the threats and opportunities related to global warming, the creation of an adaptation support fund to support local initiatives and the improvement of the institutional, regulatory and political framework.

Keywords: small and medium-sized enterprises, climate change, adaptation, semi-arid lands

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1468 Reduction of the Cellular Infectivity of SARS-CoV-2 by a Mucoadhesive Nasal Spray

Authors: Adam M. Pitz, Gillian L. Phillipson, Jayant E. Khanolkar, Andrew M. Middleton

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New emerging evidence suggests that the nose is the predominant route for entry of the SARS-CoV-2 virus into the host. A virucidal suspension test (conforming in principle to the European Standard EN14476) was conducted to determine whether a commercial liquid gel intranasal spray containing 1% of the mucoadhesive hydroxypropyl methylcellulose (HPMC) could inhibit the cellular infectivity of the SARS-CoV-2 coronavirus. Virus was added to the test product samples and to controls in a 1:8 ratio and mixed with one part bovine serum albumin as an interfering substance. The test samples were pre-equilibrated to 34 ± 2°C (representing the temperature of the nasopharynx) with the temperature maintained at 34 ± 2°C for virus contact times of 1, 5 and 10 minutes. Neutralized aliquots were inoculated onto host cells (Vero E6 cells, ATCC CRL-1586). The host cells were then incubated at 36 ± 2°C for a period of 7 days. The residual infectious virus in both test and controls was detected by viral-induced cytopathic effect. The 50% tissue culture infective dose per mL (TCID50/mL) was determined using the Spearman-Karber method with results reported as the reduction of the virus titer due to treatment with test product, expressed as log10. The controls confirmed the validity of the results with no cytotoxicity or viral interference observed in the neutralized test product samples. The HPMC formulation reduced SARS-CoV-2 titer, expressed as log10TCID50, by 2.30 ( ± 0.17), 2.60 ( ± 0.19), and 3.88 ( ± 0.19) with the respective contact times of 1, 5 and 10 minutes. The results demonstrate that this 1% HPMC gel formulation can reduce the cellular infectivity of the SARS-CoV-2 virus with an increasing viral inhibition observed with increasing exposure time. This 1% HMPC gel is well tolerated and can reside, when delivered via nasal spray, for up to one hour in the nasal cavity. We conclude that this intranasal gel spray with 1% HPMC repeat-dosed every few hours may offer an effective preventive or early intervention solution to limit the transmission and impact of the SARS-CoV-2 coronavirus.

Keywords: hydroxypropyl methylcellulose, mucoadhesive nasal spray, respiratory viruses, SARS-CoV-2

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1467 Psychological Resilience Factors Associated with Climate Change Adaptations by Subsistence Farmers in a Rural Community, South Africa

Authors: Kgopa Bontle, Tholen Sodi

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Climate change poses a major threat to the well-being of both people and the environment, with subsistence farmers most affected as they rely on local supply systems that are sensitive to climate variation. This study documented psychological resilience factors associated with climate change adaptations by subsistence farmers in Maruleng Municipality, Limpopo Province. A qualitative study was conducted to examine the notions of climate change by subsistence farmers, the psychological resilience factors, the strategies to cope with climate change, adaptation methods, and the development of subsistence farmers’ psychological resilience factors model. Data were collected through direct interactions with participants using a grounded theory research design. An open-ended interview was used to collect data with a sample of 15 participants selected through theoretical sampling in Maruleng Municipality. The participants were both Sepedi and Xitsonga speaking from 2 villages, mostly unemployed, pensioners and dependent on social grants. The study included both males and females who were predominately the elderly. The research findings indicate that farmers have limited knowledge of what climate change is and what causes it. Furthermore, the research reflects that although their responses were non-scientific but sensible enough to know what they were dealing with. They mentioned extreme weather, which includes hot days and less rainfall and changes in seasons, as some of the impacts brought by climate change. The results also indicated that participants have learned to adapt through several adaptation strategies, including mulching, changes in irrigation time slots and being innovative. The resilience factors that emerged from the study were a passion for farming, hope, enthusiasm, courage, acceptance/tolerance, livelihood and belief systems. Looking at the socio-economic factors of the current study setting argumentation leads to the conclusion that it is important that government should assist the subsistence farmers as it was observed from the participants that they felt neglected by the government and policymakers as they are small scale farmers and are not included like commercial farmers.

Keywords: climate change, psychological resilience factors, human adaptation, subsistence farmers

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1466 Climate Change Adaptation Success in a Low Income Country Setting, Bangladesh

Authors: Tanveer Ahmed Choudhury

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Background: Bangladesh is one of the largest deltas in the world, with high population density and high rates of poverty and illiteracy. 80% of the country is on low-lying floodplains, leaving the country one of the most vulnerable to the adverse effects of climate change: sea level rise, cyclones and storms, salinity intrusion, rising temperatures and heavy monsoon downpours. Such climatic events already limit Economic Development in the country. Although Bangladesh has had little responsibility in contributing to global climatic change, it is vulnerable to both its direct and indirect impacts. Real threats include reduced agricultural production, worsening food security, increased incidence of flooding and drought, spreading disease and an increased risk of conflict over scarce land and water resources. Currently, 8.3 million Bangladeshis live in cyclone high risk areas. However, by 2050 this is expected to grow to 20.3 million people, if proper adaptive actions are not taken. Under a high emissions scenario, an additional 7.6 million people will be exposed to very high salinity by 2050 compared to current levels. It is also projected that, an average of 7.2 million people will be affected by flooding due to sea level rise every year between 2070-2100 and If global emissions decrease rapidly and adaptation interventions are taken, the population affected by flooding could be limited to only about 14,000 people. To combat the climate change adverse effects, Bangladesh government has initiated many adaptive measures specially in infrastructure and renewable energy sector. Government is investing huge money and initiated many projects which have been proved very success full. Objectives: The objective of this paper is to describe some successful measures initiated by Bangladesh government in its effort to make the country a Climate Resilient. Methodology: Review of operation plan and activities of different relevant Ministries of Bangladesh government. Result: The following initiative projects, programs and activities are considered as best practices for Climate Change adaptation successes for Bangladesh: 1. The Infrastructure Development Company Limited (IDCOL); 2. Climate Change and Health Promotion Unit (CCHPU); 3. The Climate Change Trust Fund (CCTF); 4. Community Climate Change Project (CCCP); 5. Health, Population, Nutrition Sector Development Program (HPNSDP, 2011-2016)- "Climate Change and Environmental Issues"; 6. Ministry of Health and Family Welfare, Bangladesh and WHO Collaboration; - National Adaptation Plan. -"Building adaptation to climate change in health in least developed countries through resilient WASH". 7. COP-21 “Climate and health country profile -2015 Bangladesh. Conclusion: Due to a vast coastline, low-lying land and abundance of rivers, Bangladesh is highly vulnerable to climate change. Having extensive experience with facing natural disasters, Bangladesh has developed a successful adaptation program, which led to a significant reduction in casualties from extreme weather events. In a low income country setting, Bangladesh had successfully adapted various projects and initiatives to combat future Climate Change challenges.

Keywords: climate, change, success, Bangladesh

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1465 Role of Community Forestry to Address Climate Change in Nepal

Authors: Laxmi Prasad Bhattarai

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Climate change is regarded as one of the most fundamental threats to sustainable livelihood and global development. There is a growing global concern in linking community-managed forests as potential climate change mitigation projects. This study was conducted to explore local people’s perception on climate change and the role of community forestry (CF) to combat climate change impacts. Two active community forest user groups (CFUGs) from Kaski and Syangja Districts in Nepal were selected as study sites, and various participatory tools were applied to collect primary data. Although most of the respondents were unaware about the words “Climate Change” in study sites, they were quite familiar with the irregularities in rainfall season and other weather extremities. 60% of the respondents had the idea that, due to increase in precipitation, there is a frequent occurrence of erosion, floods, and landslide. Around 85% of the people agreed that community forests help in stabilizing soil, reducing the natural hazards like erosion, landslide. Biogas as an alternative source of cooking energy, and changes in crops and their varieties are the common adaptation measures that local people start practicing in both CFUGs in Nepal.

Keywords: community forestry, climate change, global warming, adaptation, Nepal

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1464 Evaluation of the Cytotoxicity and Cellular Uptake of a Cyclodextrin-Based Drug Delivery System for Cancer Therapy

Authors: Caroline Mendes, Mary McNamara, Orla Howe

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Drug delivery systems are proposed for use in cancer treatment to specifically target cancer cells and deliver a therapeutic dose without affecting normal cells. For that purpose, the use of folate receptors (FR) can be considered a key strategy, since they are commonly over-expressed in cancer cells. In this study, cyclodextrins (CD) have being used as vehicles to target FR and deliver the chemotherapeutic drug, methotrexate (MTX). CDs have the ability to form inclusion complexes, in which molecules of suitable dimensions are included within their cavities. Here, β-CD has been modified using folic acid so as to specifically target the FR. Thus, this drug delivery system consists of β-CD, folic acid and MTX (CDEnFA:MTX). Cellular uptake of folic acid is mediated with high affinity by folate receptors while the cellular uptake of antifolates, such as MTX, is mediated with high affinity by the reduced folate carriers (RFCs). This study addresses the gene (mRNA) and protein expression levels of FRs and RFCs in the cancer cell lines CaCo-2, SKOV-3, HeLa, MCF-7, A549 and the normal cell line BEAS-2B, quantified by real-time polymerase chain reaction (real-time PCR) and flow cytometry, respectively. From that, four cell lines with different levels of FRs, were chosen for cytotoxicity assays of MTX and CDEnFA:MTX using the MTT assay. Real-time PCR and flow cytometry data demonstrated that all cell lines ubiquitously express moderate levels of RFC. These experiments have also shown that levels of FR protein in CaCo-2 cells are high, while levels in SKOV-3, HeLa and MCF-7 cells are moderate. A549 and BEAS-2B cells express low levels of FR protein. FRs are highly expressed in all the cancer cell lines analysed when compared to the normal cell line BEAS-2B. The cell lines CaCo-2, MCF-7, A549 and BEAS-2B were used in the cell viability assays. 48 hours treatment with the free drug and the complex resulted in IC50 values of 93.9 µM ± 15.2 and 56.0 µM ± 4.0 for CaCo-2 for free MTX and CDEnFA:MTX respectively, 118.2 µM ± 16.8 and 97.8 µM ± 12.3 for MCF-7, 36.4 µM ± 6.9 and 75.0 µM ± 10.5 for A549 and 132.6 µM ± 16.1 and 288.1 µM ± 26.3 for BEAS-2B. These results demonstrate that free MTX is more toxic towards cell lines expressing low levels of FR, such as the BEAS-2B. More importantly, these results demonstrate that the inclusion complex CDEnFA:MTX showed greater cytotoxicity than the free drug towards the high FR expressing CaCo-2 cells, indicating that it has potential to target this receptor, enhancing the specificity and the efficiency of the drug. The use of cell imaging by confocal microscopy has allowed visualisation of FR targeting in cancer cells, as well as the identification of the interlisation pathway of the drug. Hence, the cellular uptake and internalisation process of this drug delivery system is being addressed.

Keywords: cancer treatment, cyclodextrins, drug delivery, folate receptors, reduced folate carriers

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1463 Root System Architecture Analysis of Sorghum Genotypes and Its Effect on Drought Adaptation

Authors: Hailemariam Solomon, Taye Tadesse, Daniel Nadew, Firezer Girma

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Sorghum is an important crop in semi-arid regions and has shown resilience to drought stress. However, recurrent drought is affecting its productivity. Therefore, it is necessary to explore genes that contribute to drought stress adaptation to increase sorghum productivity. The aim of this study is to evaluate and determine the effect of root system traits, specifically root angle, on drought stress adaptation and grain yield performance in sorghum genotypes. A total of 428 sorghum genotypes from the Ethiopian breeding program were evaluated in three drought-stress environments. Field trials were conducted using a row-column design with three replications. Root system traits were phenotyped using a high-throughput phenotyping platform and analyzed using a row-column design with two replications. Data analysis was performed using R software and regression analysis. The study found significant variations in root system architecture among the sorghum genotypes. Non-stay-green genotypes had a grain yield ranging from 1.63 to 3.1 tons/ha, while stay-green genotypes had a grain yield ranging from 2.4 to 2.9 tons/ha. The analysis of root angle showed that non-stay-green genotypes had an angle ranging from 8.0 to 30.5 degrees, while stay-green genotypes had an angle ranging from 12.0 to 29.0 degrees. Improved varieties exhibited angles between 14.04 and 19.50 degrees. Positive and significant correlations were observed between leaf areas and shoot dry weight, as well as between leaf width and shoot dry weight. Negative correlations were observed between root angle and leaf area, as well as between root angle and root length. This research highlights the importance of root system architecture, particularly root angle traits, in enhancing grain yield production in drought-stressed conditions. It also establishes an association between root angle and grain yield traits for maximizing sorghum productivity.

Keywords: roor sysytem architecture, root angle, narrow root angle, wider root angle, drought

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1462 Cellular Targeting to Dual Gaseous Microenvironments by Polydimethylsiloxane Microchip

Authors: Samineh Barmaki, Ville Jokinen, Esko Kankuri

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We report a microfluidic chip that can be used to modify the gaseous microenvironment of a cell-culture in ambient atmospheric conditions. The aim of the study is to show the cellular response to nitric oxide (NO) under hypoxic (oxygen < 5%) condition. Simultaneously targeting to hypoxic and nitric oxide will provide an opportunity for NO‑based therapeutics. Studies on cellular responses to lowered oxygen concentration or to gaseous mediators are usually carried out under a specific macro environment, such as hypoxia chambers, or with specific NO donor molecules that may have additional toxic effects. In our study, the chip consists of a microfluidic layer and a cell culture well, separated by a thin gas permeable polydimethylsiloxane (PDMS) membrane. The main design goal is to separate the gas oxygen scavenger and NO donor solutions, which are often toxic, from the cell media. Two different types of gas exchangers, titled 'pool' and 'meander' were tested. We find that the pool design allows us to reach a higher level of oxygen depletion than meander (24.32 ± 19.82 %vs -3.21 ± 8.81). Our microchip design can make the cells culture more simple and makes it easy to adapt existing cell culture protocols. Our first application is utilizing the chip to create hypoxic conditions on targeted areas of cell culture. In this study, oxygen scavenger sodium sulfite generates hypoxia and its effect on human embryonic kidney cells (HEK-293). The PDMS membrane was coated with fibronectin before initiating cell cultures, and the cells were grown for 48h on the chips before initiating the gas control experiments. The hypoxia experiments were performed by pumping of O₂-depleted H₂O into the microfluidic channel with a flow-rate of 0.5 ml/h. Image-iT® reagent as an oxygen level responser was mixed with HEK-293 cells. The fluorescent signal appears on cells stained with Image-iT® hypoxia reagent (after 6h of pumping oxygen-depleted H₂O through the microfluidic channel in pool area). The exposure to different levels of O₂ can be controlled by varying the thickness of the PDMS membrane. Recently, we improved the design of the microfluidic chip, which can control the microenvironment of two different gases at the same time. The hypoxic response was also improved from the new design of microchip. The cells were grown on the thin PDMS membrane for 30 hours, and with a flowrate of 0.1 ml/h; the oxygen scavenger was pumped into the microfluidic channel. We also show that by pumping sodium nitroprusside (SNP) as a nitric oxide donor activated under light and can generate nitric oxide on top of PDMS membrane. We are aiming to show cellular microenvironment response of HEK-293 cells to both nitric oxide (by pumping SNP) and hypoxia (by pumping oxygen scavenger solution) in separated channels in one microfluidic chip.

Keywords: hypoxia, nitric oxide, microenvironment, microfluidic chip, sodium nitroprusside, SNP

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1461 Translation and Adaptation of the Assessment Instrument “Kiddycat” for European Portuguese

Authors: Elsa Marta Soares, Ana Rita Valente, Cristiana Rodrigues, Filipa Gonçalves

Abstract:

Background: The assessment of feelings and attitudes of preschool children in relation to stuttering is crucial. Negative experiences can lead to anxiety, worry or frustration. To avoid the worsening of attitudes and feelings related to stuttering, it is important the early detection in order to intervene as soon as possible through an individualized intervention plan. Then it is important to have Portuguese instruments that allow this assessment. Aims: The aim of the present study is to realize the translation and adaptation of the Communication Attitude Test for Children in Preschool Age and Kindergarten (KiddyCat) for EP. Methodology: For the translation and adaptation process, a methodological study was carried out with the following steps: translation, back translation, assessment by a committee of experts and pre-test. This abstract describes the results of the first two phases of this process. The translation was accomplished by two bilingual individuals without experience in health and any knowledge about the instrument. One of them was an English teacher and the other one a Translator. The back-translation was conducted by two Senior Class Teachers that live in United Kingdom without any knowledge in health and about the instrument. Results and Discussion: In translation there were differences in semantic equivalences of various expressions and concepts. A discussion between the two translators, mediated by the researchers, allowed to achieve the consensus version of the translated instrument. Taking into account the original version of KiddyCAT the results demonstrated that back-translation versions were similar to the original version of this assessment instrument. Although the back-translators used different words, they were synonymous, maintaining semantic and idiomatic equivalences of the instrument’s items. Conclusion: This project contributes with an important resource that can be used in the assessment of feelings and attitudes of preschool children who stutter. This was the first phase of the research; expert panel and pretest are being developed. Therefore, it is expected that this instrument contributes to an holistic therapeutic intervention, taking into account the individual characteristics of each child.

Keywords: assessment, feelings and attitudes, preschool children, stuttering

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1460 Communication Anxiety in Nigerian Students Studying English as a Foreign Language: Evidence from Colleges of Education Sector

Authors: Yasàlu Haruna

Abstract:

In every transaction, the use of language is central regardless of form or complexity if any meaning is expected to be harvested therefrom. Students constituting a population group in the learning landscape of Nigeria occupy a central position with a propensity to excel or otherwise in the context of communication, especially in the learning process and social interaction. The nature or quantum of anxiety or confidence in speaking a second language is not only peculiar to societies where the second language is not an official language but to a degree, the linguistic gap created by adoption and adaptation syndrome manifests in created anxiety or lack of confidence especially where mastery of a spoken language becomes a major challenge. This paper explores the manner in which linguistic complexity and cultural barriers combine to widen the adaptation and adoption gap. In much the same way, typical issues of pronouncement, intonation and accent difficulties are vital variables that explain the root cause of anxiety. Using a combination of primary and secondary sources of data expressed in questionnaires, key informant interviews and other available data, the paper concludes that the non-integration of anxiety possibility into the education delivery framework has left a lot to be needed in cultivating second language speakers among students of Nigerian Colleges of Education. In addition, cultural barriers and the absence of integration interfaces in the course of learning within and outside the classroom contribute to further widening the gap. Again, colleagues/mates/conversation partners' mastery of a second language remains a contributory factor largely due to the quality of the preparatory school system in many parts of the country. The paper recommends that national policies and frameworks must be reviewed to consider integration windows where culture and conversation partner deficiencies can be remedied through educational events such as debates, quizzes and symposia; improvements can be attained while commercial advertisements are tailored towards seeking for adoption of second language in commerce and major cultural activities.

Keywords: cultural barriers, integration, college of education and adaptation, second language

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1459 Farmers’ Perception and Response to Climate Change Across Agro-ecological Zones in Conflict-Ridden Communities in Cameroon

Authors: Lotsmart Fonjong

Abstract:

The livelihood of rural communities in the West African state of Cameroon, which is largely dictated by natural forces (rainfall, temperatures, and soil), is today threatened by climate change and armed conflict. This paper investigates the extent to which rural communities are aware of climate change, how their perceptions of changes across different agro-ecological zones have impacted farming practices, output, and lifestyles, on the one hand, and the extent to which local armed conflicts are confounding their efforts and adaptation abilities. The paper is based on a survey conducted among small farmers in selected localities within the forest and savanna ecological zones of the conflict-ridden Northwest and Southwest Cameroon. Attention is paid to farmers’ gender, scale, and type of farming. Farmers’ perception of/and response to climate change are analysed alongside local rainfall and temperature data and mobilization for climate justice. Findings highlight the fact that farmers’ perception generally corroborates local climatic data. Climatic instability has negatively affected farmers’ output, food prices, standards of living, and food security. However, the vulnerability of the population varies across ecological zones, gender, and crop types. While these factors also account for differences in local response and adaptation to climate change, ongoing armed conflicts in these regions have further complicated opportunities for climate-driven agricultural innovations, inputs, and exchange of information among farmers. This situation underlines how poor communities, as victims, are forced into many complex problems outsider their making. It is therefore important to mainstream farmers’ perceptions and differences into policy strategies that consider both climate change and Anglophone conflict as national security concerns foe sustainable development in Cameroon.

Keywords: adaptation policies, climate change, conflict, small farmers, cameroon

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1458 The Role of Community Forestry to Combat Climate Change Impacts in Nepal

Authors: Ravi Kumar Pandit

Abstract:

Climate change is regarded as one of the most fundamental threats to sustainable livelihood and global development. There is growing a global concern in linking community-managed forests as potential climate change mitigation projects. This study was conducted to explore the local people’s perception on climate change and the role of community forestry (CF) to combat climate change impacts. Two active community forest user groups (CFUGs) from Kaski and Syangja Districts in Nepal were selected as study sites, and various participatory tools were applied to collect primary data. Although most of the respondents were unaware about the words “Climate Change” in study sites, they were quite familiar with the irregularities in rainfall season and other weather extremities. 60% of the respondents had the idea that, due to increase in precipitation, there is a frequent occurrence of erosion, floods and landslide. Around 85% of the people agreed that community forests help in stabilizing soil, reducing the natural hazards like erosion, landslide. Biogas as an alternative source of cooking energy, and changes in crops and their varieties are the common adaptation measures that local people start practicing in both CFUGs in Nepal.

Keywords: climate change, community forestry, global warming, adaptation in Nepal

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1457 Liver Regeneration of Small in situ Injury

Authors: Ziwei Song, Junjun Fan, Jeremy Teo, Yang Yu, Yukun Ma, Jie Yan, Shupei Mo, Lisa Tucker-Kellogg, Peter So, Hanry Yu

Abstract:

Liver is the center of detoxification and exposed to toxic metabolites all the time. It is highly regenerative after injury, with the ability to restore even after 70% partial hepatectomy. Most of the previous studies were using hepatectomy as injury models for liver regeneration study. There is limited understanding of small-scale liver injury, which can be caused by either low dose drug consumption or hepatocyte routine metabolism. Although these small in situ injuries do not cause immediate symptoms, repeated injuries will lead to aberrant wound healing in liver. Therefore, the cellular dynamics during liver regeneration is critical for our understanding of liver regeneration mechanism. We aim to study the liver regeneration of small-scale in situ liver injury in transgenic mice labeling actin (Lifeact-GFP). Previous studies have been using sample sections and biopsies of liver, which lack real-time information. In order to trace every individual hepatocyte during the regeneration process, we have developed and optimized an intravital imaging system that allows in vivo imaging of mouse liver for consecutive 5 days, allowing real-time cellular tracking and quantification of hepatocytes. We used femtosecond-laser ablation to make controlled and repeatable liver injury model, which mimics the real-life small in situ liver injury. This injury model is the first case of its kind for in vivo study on liver. We found that small-scale in situ liver injury is repaired by the coordination of hypertrophy and migration of hepatocytes. Hypertrophy is only transient at initial phase, while migration is the main driving force to complete the regeneration process. From cellular aspect, Akt/mTOR pathway is activated immediately after injury, which leads to transient hepatocyte hypertrophy. From mechano-sensing aspect, the actin cable, formed at apical surface of wound proximal hepatocytes, provides mechanical tension for hepatocyte migration. This study provides important information on both chemical and mechanical signals that promote liver regeneration of small in situ injury. We conclude that hypertrophy and migration play a dominant role at different stages of liver regeneration.

Keywords: hepatocyte, hypertrophy, intravital imaging, liver regeneration, migration

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1456 Rasagiline Improves Metabolic Function and Reduces Tissue Injury in the Substantia Nigra in Parkinson's Disease: A Longitudinal In-Vivo Advanced MRI Study

Authors: Omar Khan, Shana Krstevska, Edwin George, Veronica Gorden, Fen Bao, Christina Caon, NP-C, Carla Santiago, Imad Zak, Navid Seraji-Bozorgzad

Abstract:

Objective: To quantify cellular injury in the substantia nigra (SN) in patients with Parkinson's disease (PD) and to examine the effect of rasagiline of tissue injury in the SN in patients with PD. Background: N-acetylaspartate (NAA) quantified with MRS is a reliable marker of neuronal metabolic function. Fractional anisotropy (FA) and mean diffusivity (MD) obtained with DTI, characterize tissue alignment and integrity. Rasagline, has been shown to exert anti-apototic effect. We applied these advanced MRI techniques to examine: (i) the effect of rasagiline on cellular injury and metabolism in patients with early PD, and (ii) longitudinal changes seen over time in PD. Methods: We conducted a prospective longitudinal study in patients with mild PD, naive to dopaminergic treatment. The imaging protocol included multi-voxel proton-MRS and DTI of the SN, acquired on a 3T scanner. Scans were performed at baseline and month 3, during which the patient was on no treatment. At that point, rasagiline 1 mg orally daily was initiated and MRI scans are were obtained at 6 and 12 months after starting rasagiline. The primary objective was to compare changes during the 3-month period of “no treatment” to the changes observed “on treatment” with rasagiline at month 12. Age-matched healthy controls were also imaged. Image analysis was performed blinded to treatment allocation and period. Results: 25 patients were enrolled in this study. Compared to the period of “no treatment”, there was significant increase in the NAA “on treatment” period (-3.04 % vs +10.95 %, p= 0.0006). Compared to the period of “no treatment”, there was significant increase in following 12 month in the FA “on treatment” (-4.8% vs +15.3%, p<0.0001). The MD increased during “no treatment” and decreased in “on treatment” (+2.8% vs -7.5%, p=0.0056). Further analysis and clinical correlation are ongoing. Conclusions: Advanced MRI techniques quantifying cellular injury in the SN in PD is a feasible approach to investigate dopaminergic neuronal injury and could be developed as an outcome in exploratory studies. Rasagiline appears to have a stabilizing effect on dopaminergic cell loss and metabolism in the SN in PD, that warrants further investigation in long-term studies.

Keywords: substantia nigra, Parkinson's disease, MRI, neuronal loss, biomarker

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1455 The Cellular Internalization Mechanisms of Cationic Niosomes/DNA Complex in HeLa Cells

Authors: Orapan Paecharoenchai, Tanasait Ngawhirunpat, Theerasak Rojanarata, Auayporn Apirakaramwong, Praneet Opanasopit

Abstract:

Cationic niosomes formulated with Span20, cholesterol and novel synthesized spermine-cationic lipids (2-hydrocarbon tail and 4- hydrocarbon tail) in a molar ratio of 2.5:2.5:1 can mediate high gene transfection in vitro. However, the uptake mechanisms of these systems are not well clarified. In the present study, effect of endocytic inhibitors on the transfection efficiency of niosomes/DNA complexes was determined on a human cervical carcinoma cell line (HeLa cells) using the inhibitors of macropinocytosis (wortmannin), clathrin- and caveolae-mediated endocytosis (methyl-β-cyclodextrin), clathrin-mediated endocytosis (chlorpromazine), caveolae-mediated endocytosis (genistein and filipin), cytosolic transfer (ammonium chloride) and microtubules polymerization (nocodazole). The transfection of niosomes with 2-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride and filipin, respectively, whereas, the transfection of niosomes with 4-hydrocarbon tail lipid was blocked by nocodazole, genistein, ammonium chloride, methyl-β-cyclodextrin and filipin, respectively. It can be concluded that these niosomes/DNA complexes were internalized predominantly by endocytosis via clathrin and caveolae-independent pathway.

Keywords: cellular internalization, cationic niosomes, gene carriers, spermine-cationic lipids

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1454 An Algorithm Based on Control Indexes to Increase the Quality of Service on Cellular Networks

Authors: Rahman Mofidi, Sina Rahimi, Farnoosh Darban

Abstract:

Communication plays a key role in today’s world, and to support it, the quality of service has the highest priority. It is very important to differentiate between traffic based on priority level. Some traffic classes should be a higher priority than other classes. It is also necessary to give high priority to customers who have more payment for better service, however, without influence on other customers. So to realize that, we will require effective quality of service methods. To ensure the optimal performance of the network in accordance with the quality of service is an important goal for all operators in the mobile network. In this work, we propose an algorithm based on control parameters which it’s based on user feedback that aims at minimizing the access to system transmit power and thus improving the network key performance indicators and increasing the quality of service. This feedback that is known as channel quality indicator (CQI) indicates the received signal level of the user. We aim at proposing an algorithm in control parameter criterion to study improving the quality of service and throughput in a cellular network at the simulated environment. In this work we tried to parameter values have close to their actual level. Simulation results show that the proposed algorithm improves the system throughput and thus satisfies users' throughput and improves service to set up a successful call.

Keywords: quality of service, key performance indicators, control parameter, channel quality indicator

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1453 Culturable Microbial Diversity and Adaptation Strategy in the Jutulsessen and Ahlmannryggen of Western Dronning Maud Land, Antarctica

Authors: Shiv Mohan Singh, Gwyneth Matcher

Abstract:

To understand the culturable microbial composition and diversity patterns, soil samples were collected from inland nunataks of Jutulsessen and Ahlmannryggen ranges in Dronning Maud Land, Antarctica. 16S rRNA, ITS and the D1/D2 domain sequencing techniques were used for characterization of microbial communities of these geographical areas. The total 37 species of bacteria such as Arthrobacter agilis, Acinetobacter baumannii, Arthrobacter flavus, Arthrobacter ginsengisoli, Arthrobacter oxydans, Arthrobacter oryzae, Arthrobacter polychromogenes, Arthrobacter sulfonivorans, Bacillus altitudinis, Bacillus cereus, Bacillus paramycoides, Brevundimonas vesicularis, Brachybacterium rhamnosum, Curtobacterium luteum, Dermacoccus nishinomiyaensis, Dietzia aerolata, Janibacter indicus, Knoellia subterranean, Kocuria palustris, Kytococcus aerolatus, Lysinibacillus sphaericus, Microbacterium phyllosphaerae, Micrococcus yunnanensis, Methylobacterium rhodesianum, Moraxella osloensis, Paracoccus acridae, Pontibacter amylolyticus, Pseudomonas hunanensis, Pseudarthrobacter siccitolerans, Pseudarthrobacter phenanthrenivorans, Rhodococcus aerolatus, Rhodococcus sovatensis, Sphingomonas daechungensis, Sphingomonas sanguinis, Stenotrophomonas pavanii, Staphylococcus gallinarum, Staphylococcus arlettae and 9 species of fungi such as Candida davisiana, Cosmospora arxii, Geomyces destructans, Lecanicillium muscarium, Memnoniella humicola, Paecilomyces lilacinus, Pseudogymnoascus verrucosus, Phaeophlebiopsis ignerii and Thyronectria caraganae were recorded. Fatty acid methyl esters (FAME) analyses of representative species of each genus have shown predominance branched and unsaturated fatty acids indicate its adaptation strategy in Antarctic cold environment. To the best of our knowledge, this is the first record of culturable bacterial communities from Jutulsessen and Ahlmannryggen ranges in Western Dronning Maud Land, Antarctica.

Keywords: antarctica, microbe, adaptation, polar

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1452 Strategies Used by the Saffron Producers of Taliouine (Morocco) to Adapt to Climate Change

Authors: Aziz Larbi, Widad Sadok

Abstract:

In Morocco, the mountainous regions extend over about 26% of the national territory where 30% of the total population live. They contain opportunities for agriculture, forestry, pastureland and mining. The production systems in these zones are characterised by crop diversification. However, these areas have become vulnerable to the effects of climate change. To understand these effects in relation to the population living in these areas, a study was carried out in the zone of Taliouine, in the Anti-Atlas. The vulnerability of crop productions to climate change was analysed and the different ways of adaptation adopted by farmers were identified. The work was done on saffron, the most profitable crop in the target area even though it requires much water. Our results show that the majority of the farmers surveyed had noticed variations in the climate of the region: irregularity of precipitation leading to a decrease in quantity and an uneven distribution throughout the year; rise in temperature; reduction in the cold period and less snow. These variations had impacts on the cropping system of saffron and its productivity. To cope with these effects, the farmers adopted various strategies: better management and use of water; diversification of agricultural activities; increase in the contribution of non-agricultural activities to their gross income; and seasonal migration.

Keywords: climate change, Taliouine, saffron, perceptions, adaptation strategies

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1451 Engineering a Tumor Extracellular Matrix Towards an in vivo Mimicking 3D Tumor Microenvironment

Authors: Anna Cameron, Chunxia Zhao, Haofei Wang, Yun Liu, Guang Ze Yang

Abstract:

Since the first publication in 1775, cancer research has built a comprehensive understanding of how cellular components of the tumor niche promote disease development. However, only within the last decade has research begun to establish the impact of non-cellular components of the niche, particularly the extracellular matrix (ECM). The ECM, a three-dimensional scaffold that sustains the tumor microenvironment, plays a crucial role in disease progression. Cancer cells actively deregulate and remodel the ECM to establish a tumor-promoting environment. Recent work has highlighted the need to further our understanding of the complexity of this cancer-ECM relationship. In vitro models use hydrogels to mimic the ECM, as hydrogel matrices offer biological compatibility and stability needed for long term cell culture. However, natural hydrogels are being used in these models verbatim, without tuning their biophysical characteristics to achieve pathophysiological relevance, thus limiting their broad use within cancer research. The biophysical attributes of these gels dictate cancer cell proliferation, invasion, metastasis, and therapeutic response. Evaluating the three most widely used natural hydrogels, Matrigel, collagen, and agarose gel, the permeability, stiffness, and pore-size of each gel were measured and compared to the in vivo environment. The pore size of all three gels fell between 0.5-6 µm, which coincides with the 0.1-5 µm in vivo pore size found in the literature. However, the stiffness for hydrogels able to support cell culture ranged between 0.05 and 0.3 kPa, which falls outside the range of 0.3-20,000 kPa reported in the literature for an in vivo ECM. Permeability was ~100x greater than in vivo measurements, due in large part to the lack of cellular components which impede permeation. Though, these measurements prove important when assessing therapeutic particle delivery, as the ECM permeability decreased with increasing particle size, with 100 nm particles exhibiting a fifth of the permeability of 10 nm particles. This work explores ways of adjusting the biophysical characteristics of hydrogels by changing protein concentration and the trade-off, which occurs due to the interdependence of these factors. The global aim of this work is to produce a more pathophysiologically relevant model for each tumor type.

Keywords: cancer, extracellular matrix, hydrogel, microfluidic

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1450 Cellular Uptake and Endocytosis of Doxorubicin Loaded Methoxy Poly (Ethylene Glycol)-Block-Poly (Glutamic Acid) [DOX/mPEG-b-PLG] Nanoparticles against Human Breast Cancer Cell Lines

Authors: Zaheer Ahmad, Afzal Shah

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pH responsive block copolymers consist of mPEG and glutamic acid units were syntheiszed in different formulations. The synthesized polymers were structurally investigated. Doxorubicin Hydrocholide (DOX-HCl) as a chemotherapy medication for the treatment of cancer was selected. DOX-HCl was loaded and their drug loading content and drug loading efficiency were determined. The nanocarriers were obtained in small size, well shaped and slightly negative surface charge. The release study was carried out both at pH 7.4 and 5.5 and it was revealed that the release was sustained and in controlled manner and there was no initial burst release. The in vitro release study was further carried out for different formulations with different glutamic acid moieties. Time dependent cell proliferation inhibition of the free drug and drug loaded nanoparticles against human breast cancer cell lines MCF-7 and Zr-75-30 was observed. Cellular uptakes and endocytosis were investigated by confocal laser scanning microscopy (CLSM) and flow cytometery. The biocompatibility, optimum size, shape and surface charge of the developed nanoparticles make the nanoparticles an efficient drug delivery carrier.

Keywords: doxorubicin, glutamic acid, cell proliferation inhibition, breast cancer cell

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