Search results for: automated delivery cabinets

Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Mehboob Alam

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The development of efficient delivery systems remains a major concern in cancer chemotherapy as many efficacious anticancer drugs are hydrophobic and difficult to formulate. Nanomedicines based on drug-loaded amphiphilic glycol chitosan micelles offer potential advantages for the formulation of drugs such as etoposide that may improve the pharmacokinetics and reduce the formulation-related adverse effects observed with current formulations. Amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxysuccinimide and quaternization to glycol chitosan backbone. To this end, a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternization, yielding a 13 kDa amphiphilic polymer. Micelles prepared from this amphiphilic polymer had a size of 162nm and were able to encapsulate up to 3 mg/ml etoposide. Pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drugs after intravenous administration. AUC 0.5-24h showed statistically significant difference in ETP-GCPQ vs. Commercial preparation in liver (25 vs.70, p<0.001), spleen (27 vs.36, p<0.05), lungs (42 vs.136,p<0.001),kidneys(25 vs.70,p< 0.05),and brain(19 vs.9,p<0.001). ETP-GCPQ crossed the blood-brain barrier, and 4, 3.5, 2.6, 1.8, 1.7, 1.5, and 2.5 fold higher levels of etoposide were observed at 0.5, 1, 2, 4, 6, 12, and 24hrs; respectively suggesting these systems could deliver hydrophobic anticancer drugs such as etoposide to tumors but also increased their transport through the biological barriers, thus making it a good delivery system

Keywords: glycol chitosan, micelles, pharmacokinetics, tissue distribution

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Authors: Joanne Joyce-McCoach

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Short courses are an integral part of the higher education sector, providing a pathway into tertiary qualifications. Recently, the Australian government has implemented a range of initiatives to support the development of short courses and micro-credentials designed to upskill the labor market and meet the needs of the healthcare workforce. While short courses have been an ongoing component of Australian nursing continuing professional development, there is an immediate need for more education opportunities as a response to the workforce shortages. However, despite the support for short courses, there are identified challenges for learners undertaking these courses online. As a result of restrictions to face-to-face classes and limited access to health services caused by the pandemic, education providers have had to transition to an online delivery requiring the redesign of skills acquisition. This paper will outline the transition of an immunisation short course to a fully online format, including the redesign of classes, content and assessment. Concurrently the enrolments for the immunisation short course substantially increased in direct response to the demand for nurse immunisers. In addition to providing a description of the curriculum changes implemented, an analysis of learners’ feedback on their experience of the new format will be discussed. Furthermore, it will explore the principles identified in the transition process for improving the short course design and learning activities. Finally, it will propose recommendations to integrate into the delivery of online short courses and to meet the learners' needs.

Keywords: nurse, immunisation, short course, micro-credential, continuing professional development, online design

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Authors: Emily Purdom, Rachel Robinson

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As the number of students worldwide requiring speech-language therapy, occupational therapy and mental health services during their school day increases, innovation is becoming progressively more important to meet the demand. Telepractice can be used to reach a greater number of students requiring specialized therapy while maintaining the highest quality of care. It can be provided in a way that is not only effective but ultimately more convenient for student, teacher and therapist without the added burden of travel. Teletherapy eradicates many hurdles to traditional on-site service delivery and helps to solve the pervasive shortage of certified professionals. Because location is no longer a barrier to specialized education plans for students with disabilities when teletherapy is conducted, there are many advantages that can be deployed. Increased frequency of engagement is possible along with students receiving specialized care from a clinician that may not be in their direct area. Educational teams, including parents, can work together more easily and engage in face-to-face, student-centered collaboration through videoconference. Practical strategies will be provided for connecting students with qualified therapists without the typical in-person dynamic. In most cases, better therapy outcomes are going to be achieved when treatment is most convenient for the student and educator. This workshop will promote discussion in the field of education to increase advocacy for remote service delivery. It will serve as a resource for those wanting to expand their knowledge of options for students with special needs afforded through innovation.

Keywords: education technology, innovation, student support services, telepractice

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Authors: Jeffrey Ansloos

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International trauma education in low and emerging economies requires innovative methods for capacity building in existing social service infrastructures. This study details the findings of a program evaluation used to assess the learning outcomes and community impact of an international trauma-focused graduate degree program in Guyana. Through a collaborative partnership between Lesley University, the Government of Guyana, and UNICEF, a 2-year low-residency masters degree graduate program in trauma-focused assessment, intervention, and treatment was piloted with a cohort of Guyanese mental health professionals. Through an analytical review of the program development, as well as qualitative data analysis of participant interviews and focus-groups, this study will address the efficacy of the programming in terms of preparedness of professionals to understand, evaluate and implement trauma-informed practices across various child, youth, and family mental health service settings. Strengths and limitations of this international trauma-education delivery model will be discussed with particular emphasis on the role of capacity-building interventions, community-based participatory curriculum development, innovative technological delivery platforms, and interdisciplinary education. Implications for further research and subsequent program development will be discussed.

Keywords: mental health promotion, global health promotion, trauma education, innovations in education, child, youth, mental health education

Procedia PDF Downloads 367

Authors: Yun Chen, Qihang Liu, Catherine Ticehurst, Chandrama Sarker, Fazlul Karim, Dave Penton, Ashmita Sengupta

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The application of ICESAT-2 altimetry data in river hydrology critically depends on the accuracy of the mean water surface elevation (WSE) at a virtual station (VS) where satellite observations intersect with water. The ICESAT-2 track generates multiple VSs as it crosses the different water bodies. The difficulties are particularly pronounced in large river basins where there are many tributaries and meanders often adjacent to each other. One challenge is to split photon segments along a beam to accurately partition them to extract only the true representative water height for individual elements. As far as we can establish, there is no automated procedure to make this distinction. Earlier studies have relied on human intervention or river masks. Both approaches are unsatisfactory solutions where the number of intersections is large, and river width/extent changes over time. We describe here an automated approach called “auto-segmentation”. The accuracy of our method was assessed by comparison with river water level observations at 10 different stations on 37 different dates along the Lower Murray River, Australia. The congruence is very high and without detectable bias. In addition, we compared different outlier removal methods on the mean WSE calculation at VSs post the auto-segmentation process. All four outlier removal methods perform almost equally well with the same R2 value (0.998) and only subtle variations in RMSE (0.181–0.189m) and MAE (0.130–0.142m). Overall, the auto-segmentation method developed here is an effective and efficient approach to deriving accurate mean WSE at river VSs. It provides a much better way of facilitating the application of ICESAT-2 ATL13 altimetry to rivers compared to previously reported studies. Therefore, the findings of our study will make a significant contribution towards the retrieval of hydraulic parameters, such as water surface slope along the river, water depth at cross sections, and river channel bathymetry for calculating flow velocity and discharge from remotely sensed imagery at large spatial scales.

Keywords: lidar sensor, virtual station, cross section, mean water surface elevation, beam/track segmentation

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Authors: Nafiseh Mirabdolhosseini, Jerry Zhou, Vincent Ho

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The dramatic global rise in acid reflux has also led to oesophageal adenocarcinoma (OAC) becoming the fastest-growing cancer in developed countries. While gastroscopy with biopsy is used to diagnose OAC patients, this labour-intensive and expensive process is not suitable for population screening. This study aims to design, develop, and implement a minimally invasive system to capture optical data of the distal oesophagus for rapid screening of potential abnormalities. To develop the system and understand user requirements, a user-centric approach was employed by utilising co-design strategies. Target users’ segments were identified, and 38 patients and 14 health providers were interviewed. Next, the technical requirements were developed based on consultations with the industry. A minimally invasive optical system was designed and developed considering patient comfort. This system consists of the sensing catheter, controller unit, and analysis program. Its procedure only takes 10 minutes to perform and does not require cleaning afterward since it has a single-use catheter. A prototype system was evaluated for safety and efficacy for both laboratory and clinical performance. This prototype performed successfully when submerged in simulated gastric fluid without showing evidence of erosion after 24 hours. The system effectively recorded a video of the mid-distal oesophagus of a healthy volunteer (34-year-old male). The recorded images were used to develop an automated program to identify abnormalities in the distal oesophagus. Further data from a larger clinical study will be used to train the automated program. This system allows for quick visual assessment of the lower oesophagus in primary care settings and can serve as a screening tool for oesophageal adenocarcinoma. In addition, this system is able to be coupled with 24hr ambulatory pH monitoring to better correlate oesophageal physiological changes with reflux symptoms. It also can provide additional information on lower oesophageal sphincter functions such as opening times and bolus retention.

Keywords: endoscopy, MedTech, oesophageal adenocarcinoma, optical system, screening tool

Procedia PDF Downloads 88

Authors: Philipp Galkin

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Government policy is a critical factor in the understanding of energy markets. Regardless, it is rarely approached systematically from a research perspective. Gaining a precise understanding of what policies exist, their intended outcomes, geographical extent, duration, evolution, etc. would enable the research community to answer a variety of questions that, for now, are either oversimplified or ignored. Policy, on its surface, also seems a rather unstructured and qualitative undertaking. There may be quantitative components, but incorporating the concept of policy analysis into quantitative analysis remains a challenge. The KAPSARC Energy Policy Database (KEPD) is intended to address these two energy policy research limitations. Our approach is to represent policies within a quantitative library of the specific policy measures contained within a set of legal documents. Each of these measures is recorded into the database as a single entry characterized by a set of qualitative and quantitative attributes. Initially, we have focused on the major laws at the national level that regulate coal in China. However, KAPSARC is engaged in various efforts to apply this methodology to other energy policy domains. To ensure scalability and sustainability of our project, we are exploring semantic processing using automated computer algorithms. Automated coding can provide a more convenient input data for human coders and serve as a quality control option. Our initial findings suggest that the methodology utilized in KEPD could be applied to any set of energy policies. It also provides a convenient tool to facilitate understanding in the energy policy realm enabling the researcher to quickly identify, summarize, and digest policy documents and specific policy measures. The KEPD captures a wide range of information about each individual policy contained within a single policy document. This enables a variety of analyses, such as structural comparison of policy documents, tracing policy evolution, stakeholder analysis, and exploring interdependencies of policies and their attributes with exogenous datasets using statistical tools. The usability and broad range of research implications suggest a need for the continued expansion of the KEPD to encompass a larger scope of policy documents across geographies and energy sectors.

Keywords: China, energy policy, policy analysis, policy database

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Authors: Djeddi Khaled, Houssou Hind, Miloudi Abdellatif, Rabah Siham

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In the field of veterinary medicine, there is a growing application of artificial intelligence (AI) for diagnosing bovine mastitis, a prevalent inflammatory disease in dairy cattle. AI technologies, such as automated milking systems, have streamlined the assessment of key metrics crucial for managing cow health during milking and identifying prevalent diseases, including mastitis. These automated milking systems empower farmers to implement automatic mastitis detection by analyzing indicators like milk yield, electrical conductivity, fat, protein, lactose, blood content in the milk, and milk flow rate. Furthermore, reports highlight the integration of somatic cell count (SCC), thermal infrared thermography, and diverse systems utilizing statistical models and machine learning techniques, including artificial neural networks, to enhance the overall efficiency and accuracy of mastitis detection. According to a review of 15 publications, machine learning technology can predict the risk and detect mastitis in cattle with an accuracy ranging from 87.62% to 98.10% and sensitivity and specificity ranging from 84.62% to 99.4% and 81.25% to 98.8%, respectively. Additionally, machine learning algorithms and microarray meta-analysis are utilized to identify mastitis genes in dairy cattle, providing insights into the underlying functional modules of mastitis disease. Moreover, AI applications can assist in developing predictive models that anticipate the likelihood of mastitis outbreaks based on factors such as environmental conditions, herd management practices, and animal health history. This proactive approach supports farmers in implementing preventive measures and optimizing herd health. By harnessing the power of artificial intelligence, the diagnosis of bovine mastitis can be significantly improved, enabling more effective management strategies and ultimately enhancing the health and productivity of dairy cattle. The integration of artificial intelligence presents valuable opportunities for the precise and early detection of mastitis, providing substantial benefits to the dairy industry.

Keywords: artificial insemination, automatic milking system, cattle, machine learning, mastitis

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Authors: B. Tiseo, V. Quaranta, G. Bruno, G. Sisinni

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There is an increasing demand of nano-satellite development among universities, small companies, and emerging countries. Low-cost and fast-delivery are the main advantages of such class of satellites achieved by the extensive use of commercial-off-the-shelf components. On the other side, the loss of reliability and the poor success rate are limiting the use of nano-satellite to educational and technology demonstration and not to the commercial purpose. Standardization of nano-satellite environmental testing by tailoring the existing test standard for medium/large satellites is then a crucial step for their market growth. Thus, it is fundamental to find the right trade-off between the improvement of reliability and the need to keep their low-cost/fast-delivery advantages. This is particularly even more essential for satellites of CubeSat family. Such miniaturized and standardized satellites have 10 cm cubic form and mass no more than 1.33 kilograms per 1 unit (1U). For this class of nano-satellites, the qualification process is mandatory to reduce the risk of failure during a space mission. This paper reports the description and results of the space qualification test campaign performed on Endurosat’s CubeSat nano-satellite and modules. Mechanical and environmental tests have been carried out step by step: from the testing of the single subsystem up to the assembled CubeSat nano-satellite. Functional tests have been performed during all the test campaign to verify the functionalities of the systems. The test duration and levels have been selected by tailoring the European Space Agency standard ECSS-E-ST-10-03C and GEVS: GSFC-STD-7000A.

Keywords: CubeSat, nano-satellite, shock, testing, vibration

Procedia PDF Downloads 186

Authors: Funda Erdem Şahnali, Ş. Özgür Atayılmaz, Tolga N. Aynur

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Almost all of the domestic refrigerators operate on the principle of the vapor compression refrigeration cycle and removal of heat from the refrigerator cabinets is done via one of the two methods: natural convection or forced convection. In this study, airflow and temperature distributions inside a 375L no-frost type larder cabinet, in which cooling is provided by forced convection, are evaluated both experimentally and numerically. Airflow rate, compressor capacity and temperature distribution in the cooling chamber are known to be some of the most important factors that affect the cooling performance and energy consumption of a refrigerator. The objective of this study is to evaluate the original temperature distribution in the larder cabinet, and investigate for better temperature distribution solutions throughout the refrigerator domain via system optimizations that could provide uniform temperature distribution. The flow visualization and airflow velocity measurements inside the original refrigerator are performed via Stereoscopic Particle Image Velocimetry (SPIV). In addition, airflow and temperature distributions are investigated numerically with Ansys Fluent. In order to study the heat transfer inside the aforementioned refrigerator, forced convection theories covering the following cases are applied: closed rectangular cavity representing heat transfer inside the refrigerating compartment. The cavity volume has been represented with finite volume elements and is solved computationally with appropriate momentum and energy equations (Navier-Stokes equations). The 3D model is analyzed as transient, with k-ε turbulence model and SIMPLE pressure-velocity coupling for turbulent flow situation. The results obtained with the 3D numerical simulations are in quite good agreement with the experimental airflow measurements using the SPIV technique. After Computational Fluid Dynamics (CFD) analysis of the baseline case, the effects of three parameters: compressor capacity, fan rotational speed and type of shelf (glass or wire) are studied on the energy consumption; pull down time, temperature distributions in the cabinet. For each case, energy consumption based on experimental results is calculated. After the analysis, the main effective parameters for temperature distribution inside a cabin and energy consumption based on CFD simulation are determined and simulation results are supplied for Design of Experiments (DOE) as input data for optimization. The best configuration with minimum energy consumption that provides minimum temperature difference between the shelves inside the cabinet is determined.

Keywords: air distribution, CFD, DOE, energy consumption, experimental, larder cabinet, refrigeration, uniform temperature

Procedia PDF Downloads 109

Authors: S. Yesmin, N. F.Rahman, R. Akther, T. Begum, T. Tahmid, T. Chowdury, S. Afrin, J. D. Hamadani

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Abstract: Maternal depression is one of the risk factors of developmental delay in young children in low-income countries. Maternal depressions during pregnancy are rarely reported in Bangladesh. Objectives: The purpose of the present study was to examine the efficacy of a community based psychosocial intervention on women with mild to moderate depressive illness during the perinatal period and on their children from birth to 12 months on mothers’ mental status and their infants’ growth and development. Methodology: The study followed a prospective longitudinal approach with a randomized controlled design. Total 250 pregnant women aged between 15 and 40 years were enrolled in their third trimester of pregnancy of which 125 women were in the intervention group and 125 in the control group. Women in the intervention group received the “Thinking Healthy (CBT based) program” at their home setting, from their last month of pregnancy till 10 months after delivery. Their children received psychosocial stimulation from birth till 12 months. The following instruments were applied to get the outcome information- Bangla version of Edinburgh Postnatal Depression Scale (BEPDS), Prenatal Attachment Inventory (PAI), Maternal Attachment Inventory (MAI), Bayley Scale of Infant Development-Third version (Bayley–III) and Family Care Indicator (FCI). In addition, sever morbidity; breastfeeding, immunization, socio-economic and demographic information were collected. Data were collected at three time points viz. baseline, midline (6 months after delivery) and endline (12 months after delivery). Results: There was no significant difference between any of the socioeconomic and demographic variables at baseline. A very preliminary analysis of the data shows an intervention effect on Socioemotional behaviour of children at endline (p<0.001), motor development at midline (p=0.016) and at endline (p=0.065), language development at midline (p=0.004) and at endline (p=0.023), cognitive development at midline (p=0.008) and at endline (p=0.002), and quality of psychosocial stimulation at midline (p=0.023) and at endline (p=0.010). EPDS at baseline was not different between the groups (p=0.419), but there was a significant improvement at midline (p=0.027) and at endline (p=0.024) between the groups following the intervention. Conclusion: Psychosocial intervention is found effective in reducing women’s low and moderate depressive illness to cope with mental health problem and improving development of young children in Bangladesh.

Keywords: mental health, maternal depression, infant development, CBT, EPDS

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Authors: Zhiyong Li, Hiroshi Katayama

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Since 1990s, e-commerce and internet business have been grown gradually over the word and customers tend to express their demand attributes in terms of specification requirement on parts, component, product structure etc. This paper deals with designing effective decoupling points for build to order systems under e-commerce environment, which can be realized through tradeoff relation analysis between two major criteria, customer order lead time and value of work in progress. These KPIs are critical for successful BTO business, namely time-based service effectiveness on coping with customer requirements for the first issue and cost effective ness with risk aversive operations for the second issue. Approach of this paper consists of investigation of successful business standing for BTO scheme, manufacturing model development of this scheme, quantitative evaluation of proposed models by calculation of two KPI values under various decoupling point distributions and discussion of the results brought by pattern of decoupling point distribution, where some cases provide the pareto optimum performances. To extract the relevant trade-off relation between considered KPIs among 2-dimensional resultant performance, useful logic developed by former research work, i.e. Katayama and Fonseca, is applied. Obtained characteristics are evaluated as effective information for managing BTO manufacturing businesses.

Keywords: build-to-order (BTO), decoupling point, e-commerce, order-to-delivery lead time (ODLT), work in progress (WIP)

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Authors: Roberta Mugellesi Dow

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As the climate crisis becomes unignorable, it is imperative that new services are developed addressing not only the needs of customers but also taking into account its impact on the environment. The Telecommunication and Integrated Application (TIA) Directorate of ESA is supporting the green transition with particular attention to the sustainable mobility.“Accelerating the shift to sustainable and smart mobility” is at the core of the European Green Deal strategy, which seeks a 90% reduction in related emissions by 2050 . Transforming the way that people and goods move is essential to increasing mobility while decreasing environmental impact, and transport must be considered holistically to produce a shared vision of green intermodal mobility. The use of space technologies, integrated with terrestrial technologies, is an enabler of smarter traffic management and increased transport efficiency for automated and connected multimodal mobility. Satellite connectivity, including future 5G networks, and digital technologies such as Digital Twin, AI, Machine Learning, and cloud-based applications are key enablers of sustainable mobility.SatCom is essential to ensure that connectivity is ubiquitously available, even in remote and rural areas, or in case of a failure, by the convergence of terrestrial and SatCom connectivity networks, This is especially crucial when there are risks of network failures or cyber-attacks targeting terrestrial communication. SatCom ensures communication network robustness and resilience. The combination of terrestrial and satellite communication networks is making possible intelligent and ubiquitous V2X systems and PNT services with significantly enhanced reliability and security, hyper-fast wireless access, as well as much seamless communication coverage. SatNav is essential in providing accurate tracking and tracing capabilities for automated vehicles and in guiding them to target locations. SatNav can also enable location-based services like car sharing applications, parking assistance, and fare payment. In addition to GNSS receivers, wireless connections, radar, lidar, and other installed sensors can enable automated vehicles to monitor surroundings, to ‘talk to each other’ and with infrastructure in real-time, and to respond to changes instantaneously. SatEO can be used to provide the maps required by the traffic management, as well as evaluate the conditions on the ground, assess changes and provide key data for monitoring and forecasting air pollution and other important parameters. Earth Observation derived data are used to provide meteorological information such as wind speed and direction, humidity, and others that must be considered into models contributing to traffic management services. The paper will provide examples of services and applications that have been developed aiming to identify innovative solutions and new business models that are allowed by new digital technologies engaging space and non space ecosystem together to deliver value and providing innovative, greener solutions in the mobility sector. Examples include Connected Autonomous Vehicles, electric vehicles, green logistics, and others. For the technologies relevant are the hybrid satcom and 5G providing ubiquitous coverage, IoT integration with non space technologies, as well as navigation, PNT technology, and other space data.

Keywords: sustainability, connectivity, mobility, satellites

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Authors: Swapnila V. Shinde, Hemant P. Joshi, Sumit R. Dhas, Dhananjaysingh B. Rajput

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The objective of the present study is to develop hydro-dynamically balanced system for atenolol, β-blocker as a single unit floating tablet. Atenolol shows pH dependent solubility resulting into a bioavailability of 36%. Thus, site specific oral controlled release floating drug delivery system was developed. Formulation includes novice use of rate controlling polymer such as locust bean gum (LBG) in combination of HPMC K4M and gas generating agent sodium bicarbonate. Tablet was prepared by direct compression method and evaluated for physico-mechanical properties. The statistical method was utilized to optimize the effect of independent variables, namely amount of HPMC K4M, LBG and three dependent responses such as cumulative drug release, floating lag time, floating time. Graphical and mathematical analysis of the results allowed the identification and quantification of the formulation variables influencing the selected responses. To study the gastrointestinal transit of the optimized gastro-retentive formulation, in vivo gamma scintigraphy was carried out in six healthy rabbits, after radio labeling the formulation with 99mTc. The transit profiles demonstrated that the dosage form was retained in the stomach for more than 5 hrs. The study signifies the potential of the developed system for stomach targeted delivery of atenolol with improved bioavailability.

Keywords: floating tablet, factorial design, gamma scintigraphy, antihypertensive model drug, HPMC, locust bean gum

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Authors: P. Vanichkobchinda

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The Logistics Transportation techniques, Open Vehicle Routing (OVR) is an approach toward transportation cost reduction, especially for long distance pickup and delivery nodes. The outstanding characteristic of OVR is that the route starting node and ending node are not necessary the same as in typical vehicle routing problems. This advantage enables the routing to flow continuously and the vehicle does not always return to its home base. This research aims to develop a heuristic for the open vehicle routing problem with pickup and delivery under time window and loading capacity constraints to minimize the total distance. The proposed heuristic is developed based on the Insertion method, which is a simple method and suitable for the rapid calculation that allows insertion of the new additional transportation requirements along the original paths. According to the heuristic analysis, cost comparisons between the proposed heuristic and companies are using method, nearest neighbor method show that the insertion heuristic. Moreover, the proposed heuristic gave superior solutions in all types of test problems. In conclusion, the proposed heuristic can effectively and efficiently solve the open vehicle routing. The research indicates that the improvement of new transport's calculation and the open vehicle routing with "Insertion Heuristic" represent a better outcome with 34.3 percent in average. in cost savings. Moreover, the proposed heuristic gave superior solutions in all types of test problems. In conclusion, the proposed heuristic can effectively and efficiently solve the open vehicle routing.

Keywords: business competitiveness, cost reduction, SMEs, logistics transportation, VRP

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Authors: Paresh Patel, Priya Patel, Vaidehi Sorathiya, Navin Sheth

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The aim of present work was to fabricate Salmeterol Xinafoate (SX) metered dose inhaler (MDI) for asthma and to evaluate the SX loaded solid lipid nanoparticles (SLNs) for pulmonary delivery. Solid lipid nanoparticles can be used to deliver particles to the lungs via MDI. A modified solvent emulsification diffusion technique was used to prepare Salmeterol Xinafoate loaded solid lipid nanoparticles by using compritol 888 ATO as lipid, tween 80 as surfactant, D-mannitol as cryoprotecting agent and L-leucine was used to improve aerosolization behaviour. Box-Behnken design was applied with 17 runs. 3-D surface response plots and contour plots were drawn and optimized formulation was selected based on minimum particle size and maximum % EE. % yield, in vitro diffusion study, scanning electron microscopy, X-ray diffraction, DSC, FTIR also characterized. Particle size, zeta potential analyzed by Zetatrac particle size analyzer and aerodynamic properties was carried out by cascade impactor. Pre convulsion time was examined for control group, treatment group and compare with marketed group. MDI was evaluated for leakage test, flammability test, spray test and content per puff. By experimental design, particle size and % EE found to be in range between 119-337 nm and 62.04-76.77% by solvent emulsification diffusion technique. Morphologically, particles have spherical shape and uniform distribution. DSC & FTIR study showed that no interaction between drug and excipients. Zeta potential shows good stability of SLNs. % respirable fraction found to be 52.78% indicating reach to the deep part of lung such as alveoli. Animal study showed that fabricated MDI protect the lungs against histamine induced bronchospasm in guinea pigs. MDI showed sphericity of particle in spray pattern, 96.34% content per puff and non-flammable. SLNs prepared by Solvent emulsification diffusion technique provide desirable size for deposition into the alveoli. This delivery platform opens up a wide range of treatment application of pulmonary disease like asthma via solid lipid nanoparticles.

Keywords: salmeterol xinafoate, solid lipid nanoparticles, box-behnken design, solvent emulsification diffusion technique, pulmonary delivery

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Authors: Vahid Bairami Rad

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The intelligentization of agricultural fields can control the temperature, humidity, and variables affecting the growth of agricultural products online and on a mobile phone or computer. Smarting agricultural fields and gardens is one of the best and best ways to optimize agricultural equipment and has a 100 percent direct effect on the growth of plants and agricultural products and farms. Smart farms are the topic that we are going to discuss today, the Internet of Things and artificial intelligence. Agriculture is becoming smarter every day. From large industrial operations to individuals growing organic produce locally, technology is at the forefront of reducing costs, improving results and ensuring optimal delivery to market. A key element to having a smart agriculture is the use of useful data. Modern farmers have more tools to collect intelligent data than in previous years. Data related to soil chemistry also allows people to make informed decisions about fertilizing farmland. Moisture meter sensors and accurate irrigation controllers have made the irrigation processes to be optimized and at the same time reduce the cost of water consumption. Drones can apply pesticides precisely on the desired point. Automated harvesting machines navigate crop fields based on position and capacity sensors. The list goes on. Almost any process related to agriculture can use sensors that collect data to optimize existing processes and make informed decisions. The Internet of Things (IoT) is at the center of this great transformation. Internet of Things hardware has grown and developed rapidly to provide low-cost sensors for people's needs. These sensors are embedded in IoT devices with a battery and can be evaluated over the years and have access to a low-power and cost-effective mobile network. IoT device management platforms have also evolved rapidly and can now be used securely and manage existing devices at scale. IoT cloud services also provide a set of application enablement services that can be easily used by developers and allow them to build application business logic. Focus on yourself. These development processes have created powerful and new applications in the field of Internet of Things, and these programs can be used in various industries such as agriculture and building smart farms. But the question is, what makes today's farms truly smart farms? Let us put this question in another way. When will the technologies associated with smart farms reach the point where the range of intelligence they provide can exceed the intelligence of experienced and professional farmers?

Keywords: food security, IoT automation, wireless communication, hybrid lifestyle, arduino Uno

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Authors: Haile F. Darge, Hsieh C. Tsai

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The tumor microenvironment affects the therapeutic outcomes of cancer disease. In a malignant tumor, overexpression of vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks. This results in a hostile tumor environment that hinders anti-cancer drug activities and profoundly fuels tumor progression. In this study, we develop a strategy of sequential sustain release of the anti-angiogenic drug: Bevacizumab(BVZ), and anti-cancer drug: Doxorubicin(DOX) which had a synergistic effect on cancer treatment. Poly (D, L-Lactide)- Poly (ethylene glycol) –Poly (D, L-Lactide) (PDLLA-PEG-PDLLA) thermo-sensitive hydrogel was used as a vehicle for local delivery of drugs in a single platform. The in vitro release profiles of the drugs were investigated and confirmed a relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) for a prolonged period. The cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. The in vivo study on Hela xenograft nude mice verified that hydrogel co-loaded with BVZ and DOX displayed the highest tumor suppression efficacy for up to 36 days with pronounce anti-angiogenic effect of BVZ and with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drugs by the hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.

Keywords: anti-angiogenesis, chemotherapy, controlled release, thermo-sensitive hydrogel

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Authors: Nicolay Zarutskiy, Roman Bulkin

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The paper deals with the existing methods of force-torque sensor calibration with a number of components from one to six, analyzed their advantages and disadvantages, the necessity of introduction of a calibration method. Calibration method and its constructive realization are also described here. A calibration method allows performing automated force-torque sensor calibration both with selected components of the main vector of forces and moments and with complex loading. Thus, two main advantages of the proposed calibration method are achieved: the automation of the calibration process and universality.

Keywords: automation, calibration, calibration device, calibration method, force-torque sensors

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Authors: Mohd Noah A. Rahman, Armandurni Abd Rahman, Afzaal H. Seyal, Md Rizal Md Hendry

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The article reports an automated student attendance system modeled and developed for use at a Vocational school. This project focuses on developing an application using a QR code utilizing the Reed-Solomon error correction code using a smartphone scanned through a webcam. This system enables us to speed up the process of taking attendance and would save us valuable teaching time. This is planned to help students avoid consequences that may result from poor attendances which will eventually penalize them from sitting their final examination as required.

Keywords: QR code, Reed-Solomon, error correction, system design.

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Authors: Nurkhairul Bariyah Baharun, Afzan Adam, Reena Rahayu Md Zin

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Tumor microenvironment (TME) in breast cancer is mainly composed of cancer cells, immune cells, and stromal cells. The interaction between cancer cells and their microenvironment plays an important role in tumor development, progression, and treatment response. The TME in breast cancer includes tumor-infiltrating lymphocytes (TILs) that are implicated in killing tumor cells. TILs can be found in tumor stroma (sTILs) and within the tumor (iTILs). TILs in triple negative breast cancer (TNBC) have been demonstrated to have prognostic and potentially predictive value. The international Immune-Oncology Biomarker Working Group (TIL-WG) had developed a guideline focus on the assessment of sTILs using hematoxylin and eosin (H&E)-stained slides. According to the guideline, the pathologists use “eye balling” method on the H&E stained- slide for sTILs assessment. This method has low precision, poor interobserver reproducibility, and is time-consuming for a comprehensive evaluation, besides only counted sTILs in their assessment. The TIL-WG has therefore recommended that any algorithm for computational assessment of TILs utilizing the guidelines provided to overcome the limitations of manual assessment, thus providing highly accurate and reliable TILs detection and classification for reproducible and quantitative measurement. This study is carried out to develop a TNBC digital whole slide image (WSI) dataset from H&E-stained slides and IHC (CD4+ and CD8+) stained slides. TNBC cases were retrieved from the database of the Department of Pathology, Hospital Canselor Tuanku Muhriz (HCTM). TNBC cases diagnosed between the year 2010 and 2021 with no history of other cancer and available block tissue were included in the study (n=58). Tissue blocks were sectioned approximately 4 µm for H&E and IHC stain. The H&E staining was performed according to a well-established protocol. Indirect IHC stain was also performed on the tissue sections using protocol from Diagnostic BioSystems PolyVue™ Plus Kit, USA. The slides were stained with rabbit monoclonal, CD8 antibody (SP16) and Rabbit monoclonal, CD4 antibody (EP204). The selected and quality-checked slides were then scanned using a high-resolution whole slide scanner (Pannoramic DESK II DW- slide scanner) to digitalize the tissue image with a pixel resolution of 20x magnification. A manual TILs (sTILs and iTILs) assessment was then carried out by the appointed pathologist (2 pathologists) for manual TILs scoring from the digital WSIs following the guideline developed by TIL-WG 2014, and the result displayed as the percentage of sTILs and iTILs per mm² stromal and tumour area on the tissue. Following this, we aimed to develop an automated digital image scoring framework that incorporates key elements of manual guidelines (including both sTILs and iTILs) using manually annotated data for robust and objective quantification of TILs in TNBC. From the study, we have developed a digital dataset of TNBC H&E and IHC (CD4+ and CD8+) stained slides. We hope that an automated based scoring method can provide quantitative and interpretable TILs scoring, which correlates with the manual pathologist-derived sTILs and iTILs scoring and thus has potential prognostic implications.

Keywords: automated quantification, digital pathology, triple negative breast cancer, tumour infiltrating lymphocytes

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Authors: Inês N. Peça , A. Bicho, Rui Gardner, M. Margarida Cardoso

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Inorganic/organic nanocomplexes offer tremendous scope for future biomedical applications, including imaging, disease diagnosis and drug delivery. The combination of Fe3O4 with biocompatible polymers to produce smart drug delivery systems for use in pharmaceutical formulation present a powerful tool to target anti-cancer drugs to specific tumor sites through the application of an external magnetic field. In the present study, we focused on the evaluation of the effect of the magnetic field application time on the rate of drug release from iron oxide polymeric nanoparticles. Doxorubicin, an anticancer drug, was selected as the model drug loaded into the nanoparticles. Nanoparticles composed of poly(d-lactide-co-glycolide (PLGA), a biocompatible polymer already approved by FDA, containing iron oxide nanoparticles (MNP) for magnetic targeting and doxorubicin (DOX) were synthesized by the o/w solvent extraction/evaporation method and characterized by scanning electron microscopy (SEM), by dynamic light scattering (DLS), by inductively coupled plasma-atomic emission spectrometry and by Fourier transformed infrared spectroscopy. The produced particles yielded smooth surfaces and spherical shapes exhibiting a size between 400 and 600 nm. The effect of the magnetic doxorubicin loaded PLGA nanoparticles produced on cell viability was investigated in mammalian CHO cell cultures. The results showed that unloaded magnetic PLGA nanoparticles were nontoxic while the magnetic particles without polymeric coating show a high level of toxicity. Concerning the therapeutic activity doxorubicin loaded magnetic particles cause a remarkable enhancement of the cell inhibition rates compared to their non-magnetic counterpart. In vitro drug release studies performed under a non-permanent magnetic field show that the application time and the on/off cycle duration have a great influence with respect to the final amount and to the rate of drug release. In order to determine the mechanism of drug release, the data obtained from the release curves were fitted to the semi-empirical equation of the the Korsmeyer-Peppas model that may be used to describe the Fickian and non-Fickian release behaviour. Doxorubicin release mechanism has shown to be governed mainly by Fickian diffusion. The results obtained show that the rate of drug release from the produced magnetic nanoparticles can be modulated through the magnetic field time application.

Keywords: drug delivery, magnetic nanoparticles, PLGA nanoparticles, controlled release rate

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Authors: Rita Ghosh, Joykrishna Dey

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PEG-based amphiphiles are of tremendous importance for its widespread applications in pharmaceutics, household purposes, and drug delivery. Previously, a number of single PEG-tailed amphiphiles having significant applications have been reported from our group. Therefore, it was of immense interest to explore the properties and application potential of PEG-based double tailed amphiphiles. Herein, for the first time, two novel double PEG-tailed amphiphiles having different PEG chain lengths have been developed. The self-assembly behavior of the newly developed amphiphiles in aqueous buffer (pH 7.0) was thoroughly investigated at 25 oC by a number of techniques including, 1H-NMR, and steady-state and time-dependent fluorescence spectroscopy, dynamic light scattering, transmission electron microscopy, atomic force microscopy, and isothermal titration calorimetry. Despite having two polar PEG chains both molecules were found to have strong tendency to self-assemble in aqueous buffered solution above a very low concentration. Surprisingly, the amphiphiles were shown to form stable vesicles spontaneously at room temperature without any external stimuli. The results of calorimetric measurements showed that the vesicle formation is driven by the hydrophobic effect (positive entropy change) of the system, which is associated with the helix-to-random coil transition of the PEG chain. The spectroscopic data confirmed that the bilayer membrane of the vesicles is constituted by the PEG chains of the amphiphilic molecule. Interestingly, the vesicles were also found to exhibit structural transitions upon addition of salts in solution. These properties of the vesicles enable them as potential candidate for drug delivery.

Keywords: double-tailed amphiphiles, fluorescence, microscopy, PEG, vesicles

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Authors: Yong Zhang

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Light has proven to be useful in a wide range of biomedical applications such as fluorescence imaging, photoacoustic imaging, optogenetics, photodynamic therapy, photothermal therapy, and light controlled drug/gene delivery. Taking photodynamic therapy (PDT) as an example, PDT has been proven clinically effective in early lung cancer, bladder cancer, head, and neck cancer and is the primary treatment for skin cancer as well. However, clinical use of PDT is severely constrained by the low penetration depth of visible light through thick tissue, limiting its use to target regions only a few millimeters deep. One way to enhance the range is to use invisible near-infrared (NIR) light within the optical window (700–1100nm) for biological tissues, extending the depth up to 1cm with no observable damage to the intervening tissue. We have demonstrated use of NIR-to-visible upconversion fluorescent nanoparticles (UCNPs), emitting visible fluorescence when excited by a NIR light at 980nm, as a nanotransducer for PDT to convert deep tissue-penetrating NIR light to visible light suitable for activating photosensitizers. The unique optical properties of UCNPs enable the upconversion wavelength to be tuned and matched to the activation absorption wavelength of the photosensitizer. At depths beyond 1cm, however, tissue remains inaccessible to light even within the NIR window, and this critical depth limitation renders existing phototherapy ineffective against most deep-seated cancers. We have demonstrated some new treatment modalities for deep-seated cancers based on UCNP hydrogel implants and miniaturized, wirelessly powered optoelectronic devices for light delivery to deep tissues.

Keywords: upconversion, fluorescent, nanoparticle, bioimaging, photodynamic therapy

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Authors: Kyou Hee Shim, Hwa Sung Shin

Abstract:

When a thrombolysis agent is administered to treat ischemic stroke, excessive reactive oxygen species are generated due to a sudden provision of oxygen and occurs secondary damage cell necrosis. Thus, it is necessary to administrate adjuvant as well as thrombolysis agent to protect and reduce damaged tissue. As cerebral blood vessels have specific structure called blood-brain barrier (BBB), it is not easy to transfer substances from blood to tissue. Therefore, development of a drug carrier is required to increase drug delivery efficiency to brain tissue. In this study, cyanobacterial pigment from the blue-green algae known for having neuroprotective effect as well as antioxidant effect was nasally administrated for bypassing BBB. In order to deliver cyanobacterial pigment efficiently, the nano-sized liposome was used as a carrier. Liposomes were coated with a positive charge of chitosan since negative residues are present at the nasal mucosa the first gateway of nasal administration. Characteristics of liposome including morphology, size and zeta potential were analyzed by transmission electron microscope (TEM) and zeta analyzer. As a result of cytotoxic test, the liposomes were not harmful. Also, being administered a drug to the ischemic stroke animal model, we could confirm that the pharmacological effect of the pigment delivered by chitosan coated liposome was enhanced compared to that of non-coated liposome. Consequently, chitosan coated liposome could be considered as an optimized drug delivery system for the treatment of acute ischemic stroke.

Keywords: ischemic stroke, cyanobacterial pigment, liposome, chitosan, nasal administration

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Authors: Saradiya Mukherjee

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Background: Indian Muslims, compared to their counterparts in other religions, generally do not fare well on many yardsticks related to socio-economic progress and the same is true with maternal health care utilization. Due to low age at marriage a major percentage of child birth is ascribed to young (15-24 years) Muslim mothers in, which pose serious concerns on the maternal health care of Young Married Muslim women (YMMW). A thorough search of past literature on Muslim women’s health and health care reveals that studies in India have mainly focused on religious differences in fertility levels and contraceptive use while the research on the determinants of maternal health care utilization among Muslim women are lacking in India. Data and Methods: Retrieving data from the National Family Health Survey -3 (2005-06) this study attempts to assess the level of utilization and factors effecting three key maternal health indicators (full ANC, safe delivery and PNC) among YMMW (15-24 years) in India. The key socio-economic and demographic variables taken as independent or predictor variables in the study was guided by existing literature particularly for India. Bi-variate analysis and chi square test was applied and variables which were found to be significant were further included in binary logistic regression. Results: The findings of the study reveal abysmally low levels of utilization for all three indicators i.e. full ANC, safe delivery and PNC of maternal health care included in the study. Mother’s education, mass media exposure, women’s autonomy, birth order, economic status wanted status of child and region of residence were found to be significant variables effecting maternal health care utilization among YMMW. Multivariate analysis reveals that no mass media exposure, lower autonomy, education, poor economic background, higher birth order and unintended pregnancy are some of the reasons behind low maternal health care utilization. Conclusion: Considering the low level of safe maternal health care utilization and its proximate determinants among YMMW the study suggests educating Muslim girls, promoting family planning use, involving media and collaboration between religious leader and health care system could be some important policy level interventions to address the unmet need of maternity services among YMMW.

Keywords: young Muslim women, religion, socio-economic condition, antenatal care, delivery, post natal care

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Authors: Jane E. A. Lewis, Paul Williams, Jane H. Davies

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Introduction: There is, at present, a clear and recognized need to optimize the diagnosis of peripheral arterial disease (PAD), particularly in non-specialist settings such as primary care, and this arises from several key facts. Firstly, PAD is a highly prevalent condition. In 2010, it was estimated that globally, PAD affected more than 202 million people and furthermore, this prevalence is predicted to further escalate. The disease itself, although frequently asymptomatic, can cause considerable patient suffering with symptoms such as lower limb pain, ulceration, and gangrene which, in worse case scenarios, can necessitate limb amputation. A further and perhaps the most eminent consequence of PAD arises from the fact that it is a manifestation of systemic atherosclerosis and therefore is a powerful predictor of coronary heart disease and cerebrovascular disease. Objective: This cross sectional study aimed to individually and cumulatively compare sensitivity and specificity of the (i) ankle brachial index (ABI) and (ii) pulse volume waveform (PVW) recorded by the same automated device, with the presence or absence of peripheral arterial disease (PAD) being verified by an Ultrasound Duplex Scan (UDS). Methods: Patients (n = 205) referred for lower limb arterial assessment underwent an ABI and PVW measurement using volume plethysmography followed by a UDS. Presence of PAD was recorded for ABI if < 0.9 (noted if > 1.30) if PVW was graded as 2, 3 or 4 or a hemodynamically significant stenosis > 50% with UDS. Outcome measure was agreement between measured ABI and interpretation of the PVW for PAD diagnosis, using UDS as the reference standard. Results: Sensitivity of ABI was 80%, specificity 91%, and overall accuracy 88%. Cohen’s kappa revealed good agreement between ABI and UDS (k = 0.7, p < .001). PVW sensitivity 97%, specificity 81%, overall accuracy 84%, with a good level of agreement between PVW and UDS (k = 0.67, p < .001). The combined sensitivity of ABI and PVW was 100%, specificity 76%, and overall accuracy 85% (k = 0.67, p < .001). Conclusions: Combing these two diagnostic modalities within one device provided a highly accurate method of ruling out PAD. Such a device could be utilized within the primary care environment to reduce the number of unnecessary referrals to secondary care with concomitant cost savings, reduced patient inconvenience, and prioritization of urgent PAD cases.

Keywords: ankle brachial index, peripheral arterial disease, pulse volume waveform, ultrasound duplex scan

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Authors: Saroj Bijarnia, Preety Singh

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We propose a simple and effective biometrics system based on face verification across aging using a new variant of texture feature, Pyramid Binary Pattern. This employs Local Binary Pattern along with its hierarchical information. Dimension reduction of generated texture feature vector is done using Principal Component Analysis. Support Vector Machine is used for classification. Our proposed method achieves an accuracy of 92:24% and can be used in an automated age-invariant face verification system.

Keywords: biometrics, age invariant, verification, support vector machine

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Authors: Anurag Gaur Nidhi

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Targeted drug delivery is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. Targeted drug delivery seeks to concentrate the medication in the tissues of interest while reducing the relative concentration of the medication in the remaining tissues. This improves efficacy of the while reducing side effects. In the present work, we investigate the effect of magnetic field, flow rate and particle concentration on the capturing of magnetic particles transported in a stent implanted fluidic channel. Iron oxide magnetic nanoparticles (Fe3O4) nanoparticles were synthesized via co-precipitation method. The synthesized Fe3O4 nanoparticles were added in the de-ionized (DI) water to prepare the Fe3O4 magnetic particle suspended fluid. This fluid is transported in a cylindrical tube of diameter 8 mm with help of a peristaltic pump at different flow rate (25-40 ml/min). A ferromagnetic coil of SS 430 has been implanted inside the cylindrical tube to enhance the capturing of magnetic nanoparticles under magnetic field. The capturing of magnetic nanoparticles was observed at different magnetic magnetic field, flow rate and particle concentration. It is observed that capture efficiency increases from 47-67 % at magnetic field 2-5kG, respectively at particle concentration 0.6 mg/ml and at flow rate 30 ml/min. However, the capture efficiency decreases from 65 to 44 % by increasing the flow rate from 25 to 40 ml/min, respectively. Furthermore, it is observed that capture efficiency increases from 51 to 67 % by increasing the particle concentration from 0.3 to 0.6 mg/ml, respectively.

Keywords: capture efficiency, implant assisted-Magnetic drug targeting (IA-MDT), magnetic nanoparticles, In-vitro study

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Authors: Ernest Moles, Patricia Urbán, María Belén Jiménez-Díaz, Sara Viera-Morilla, Iñigo Angulo-Barturen, Maria Antònia Busquets, Xavier Fernàndez-Busquets

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Bearing in mind the absence of an effective vaccine against malaria and its severe clinical manifestations causing nearly half a million deaths every year, this disease represents nowadays a major threat to life. Besides, the basic rationale followed by currently marketed antimalarial approaches is based on the administration of drugs on their own, promoting the emergence of drug-resistant parasites owing to the limitation in delivering drug payloads into the parasitized erythrocyte high enough to kill the intracellular pathogen while minimizing the risk of causing toxic side effects to the patient. Such dichotomy has been successfully addressed through the specific delivery of immunoliposome (iLP)-encapsulated antimalarials to Plasmodium falciparum-infected red blood cells (pRBCs). Unfortunately, this strategy has not progressed towards clinical applications, whereas in vitro assays rarely reach drug efficacy improvements above 10-fold. Here, we show that encapsulation efficiencies reaching >96% can be achieved for the weakly basic drugs chloroquine (CQ) and primaquine using the pH gradient active loading method in liposomes composed of neutrally charged, saturated phospholipids. Targeting antibodies are best conjugated through their primary amino groups, adjusting chemical crosslinker concentration to retain significant antigen recognition. Antigens from non-parasitized RBCs have also been considered as targets for the intracellular delivery of drugs not affecting the erythrocytic metabolism. Using this strategy, we have obtained unprecedented nanocarrier targeting to early intraerythrocytic stages of the malaria parasite for which there is a lack of specific extracellular molecular tags. Polyethylene glycol-coated liposomes conjugated with monoclonal antibodies specific for the erythrocyte surface protein glycophorin A (anti-GPA iLP) were capable of targeting 100% RBCs and pRBCs at the low concentration of 0.5 μM total lipid in the culture, with >95% of added iLPs retained into the cells. When exposed for only 15 min to P. falciparum in vitro cultures synchronized at early stages, free CQ had no significant effect over parasite viability up to 200 nM drug, whereas iLP-encapsulated 50 nM CQ completely arrested its growth. Furthermore, when assayed in vivo in P. falciparum-infected humanized mice, anti-GPA iLPs cleared the pathogen below detectable levels at a CQ dose of 0.5 mg/kg. In comparison, free CQ administered at 1.75 mg/kg was, at most, 40-fold less efficient. Our data suggest that this significant improvement in drug antimalarial efficacy is in part due to a prophylactic effect of CQ found by the pathogen in its host cell right at the very moment of invasion.

Keywords: immunoliposomal nanoparticles, malaria, prophylactic-therapeutic polyvalent activity, targeted drug delivery

Procedia PDF Downloads 375