Search results for: explosive detection devices

Authors: Irina Veselova, Maria Makedonskaya, Olga Eremina, Alexandr Sidorov, Eugene Goodilin, Tatyana Shekhovtsova

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Such catecholamines as dopamine, norepinephrine, and epinephrine are the principal neurotransmitters in the sympathetic nervous system. Catecholamines and their metabolites are considered to be important markers of socially significant diseases such as atherosclerosis, diabetes, coronary heart disease, carcinogenesis, Alzheimer's and Parkinson's diseases. Currently, neurotransmitters can be studied via electrochemical and chromatographic techniques that allow their characterizing and quantification, although these techniques can only provide crude spatial information. Besides, the difficulty of catecholamine determination in biological materials is associated with their low normal concentrations (~ 1 nM) in biomaterials, which may become even one more order lower because of some disorders. In addition, in blood they are rapidly oxidized by monoaminooxidases from thrombocytes and, for this reason, the determination of neurotransmitter metabolism indicators in an organism should be very rapid (15—30 min), especially in critical states. Unfortunately, modern instrumental analysis does not offer a complex solution of this problem: despite its high sensitivity and selectivity, HPLC-MS cannot provide sufficiently rapid analysis, while enzymatic biosensors and immunoassays for the determination of the considered analytes lack sufficient sensitivity and reproducibility. Fluorescent and SERS-sensors remain a compelling technology for approaching the general problem of selective neurotransmitter detection. In recent years, a number of catecholamine sensors have been reported including RNA aptamers, fluorescent ribonucleopeptide (RNP) complexes, and boronic acid based synthetic receptors and the sensor operated in a turn-off mode. In this work we present the fluorescent and SERS turn-on sensor systems based on the bio- or chemorecognizing nanostructured films {chitosan/collagen-Tb/Eu/Cu-nanoparticles-indicator reagents} that provide the selective recognition, visualization, and sensing of the above mentioned catecholamines on the level of nanomolar concentrations in biomaterials (cell cultures, tissue etc.). We have (1) developed optically transparent porous films and gels of chitosan/collagen; (2) ensured functionalization of the surface by molecules-'recognizers' (by impregnation and immobilization of components of the indicator systems: biorecognizing and auxiliary reagents); (3) performed computer simulation for theoretical prediction and interpretation of some properties of the developed materials and obtained analytical signals in biomaterials. We are grateful for the financial support of this research from Russian Foundation for Basic Research (grants no. 15-03-05064 a, and 15-29-01330 ofi_m).

Keywords: biomaterials, fluorescent and SERS-recognition, neurotransmitters, solid-phase turn-on sensor system

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Authors: Simon Caba, Raja Abou Ackl, Svend Rasmussen, Nicholas E. Pedersen

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It is a challenge to directly monitor cavitation in a pump application during operation because of a lack of visual access to validate the presence of cavitation and its form of appearance. In this work, experimental investigations are carried out in an inline single-stage centrifugal pump with optical access. Hence, it gives the opportunity to enhance the value of CFD tools and standard cavitation measurements. Experiments are conducted using two impellers running in the same volute at 3000 rpm and the same flow rate. One of the impellers used is optimized for lower NPSH₃% by its blade design, whereas the other one is manufactured using a standard casting method. The cavitation is detected by pump performance measurements, vibration measurements and high-speed image recordings. The head drop and the pump casing vibration caused by cavitation are correlated with the visual appearance of the cavitation. The vibration data is recorded in an axial direction of the impeller using accelerometers recording at a sample rate of 131 kHz. The vibration frequency domain data (up to 20 kHz) and the time domain data are analyzed as well as the root mean square values. The high-speed recordings, focusing on the impeller suction side, are taken at 10,240 fps to provide insight into the flow patterns and the cavitation behavior in the rotating impeller. The videos are synchronized with the vibration time signals by a trigger signal. A clear correlation between cloud collapses and abrupt peaks in the vibration signal can be observed. The vibration peaks clearly indicate cavitation, especially at higher NPSHA values where the hydraulic performance is not affected. It is also observed that below a certain NPSHA value, the cavitation started in the inlet bend of the pump. Above this value, cavitation occurs exclusively on the impeller blades. The impeller optimized for NPSH₃% does show a lower NPSH₃% than the standard impeller, but the head drop starts at a higher NPSHA value and is more gradual. Instabilities in the head drop curve of the optimized impeller were observed in addition to a higher vibration level. Furthermore, the cavitation clouds on the suction side appear more unsteady when using the optimized impeller. The shape and location of the cavitation are compared to 3D fluid flow simulations. The simulation results are in good agreement with the experimental investigations. In conclusion, these investigations attempt to give a more holistic view on the appearance of cavitation by comparing the head drop, vibration spectral data, vibration time signals, image recordings and simulation results. Data indicates that a criterion for cavitation detection could be derived from the vibration time-domain measurements, which requires further investigation. Usually, spectral data is used to analyze cavitation, but these investigations indicate that the time domain could be more appropriate for some applications.

Keywords: cavitation, centrifugal pump, head drop, high-speed image recordings, pump vibration

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Authors: Michael Brave, Mark Kroll, Steven Karch, Charles Wetli, Michael Graham, Sebastian Kunz, Dorin Panescu

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Background: Conducted electrical weapons (CEW) are now used in 107 countries and are a common law enforcement less-lethal force practice in the United Kingdom (UK), United States of America (USA), Canada, Australia, New Zealand, and others. Use of these devices is rarely temporally associated with the occurrence of sudden arrest-related deaths (ARD). Because such deaths are uncommon, few Medical Examiners (MEs) ever encounter one, and even fewer offices have established comprehensive investigative protocols. Without sufficient scientific data, the role, if any, played by a CEW in a given case is largely supplanted by conjecture often defaulting to a CEW-induced fatal cardiac arrhythmia. In addition to the difficulty in investigating individual deaths, the lack of information also detrimentally affects being able to define and evaluate the ARD cohort generally. More comprehensive, better information leads to better interpretation in individual cases and also to better research. The purpose of this presentation is to provide MEs with a comprehensive evidence-based checklist to assist in the assessment of CEW-ARD cases. Methods: PUBMED and Sociology/Criminology data bases were queried to find all medical, scientific, electrical, modeling, engineering, and sociology/criminology peer-reviewed literature for mentions of CEW or synonymous terms. Each paper was then individually reviewed to identify those that discussed possible bioelectrical mechanisms relating CEW to ARD. A Naranjo-type pharmacovigilance algorithm was also employed, when relevant, to identify and quantify possible direct CEW electrical myocardial stimulation. Additionally, CEW operational manuals and training materials were reviewed to allow incorporation of CEW-specific technical parameters. Results: Total relevant PUBMED citations of CEWs were less than 250, and reports of death extremely rare. Much relevant information was available from Sociology/Criminology data bases. Once the relevant published papers were identified, and reviewed, we compiled an annotated checklist of data that we consider critical to a thorough CEW-involved ARD investigation. Conclusion: We have developed an evidenced-based checklist that can be used by MEs and their staffs to assist them in identifying, collecting, documenting, maintaining, and objectively analyzing the role, if any, played by a CEW in any specific case of sudden death temporally associated with the use of a CEW. Even in cases where the collected information is deemed by the ME as insufficient for formulating an opinion or diagnosis to a reasonable degree of medical certainty, information collected as per the checklist will often be adequate for other stakeholders to use as a basis for informed decisions. Having reviewed the appropriate materials in a significant number of cases careful examination of the heart and brain is likely adequate. Channelopathy testing should be considered in some cases, however it may be considered cost prohibitive (aprox $3000). Law enforcement agencies may want to consider establishing a reserve fund to help manage such rare cases. The expense may stay the enormous costs associated with incident-precipitated litigation.

Keywords: ARD, CEW, police, TASER

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Authors: Monika Soni, Chandra Bhattacharya, Siraj Ahmed Ahmed, Prafulla Dutta

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Dengue is now a globally important arboviral disease. Extensive vector surveillance has already established A.aegypti as a primary vector, but A.albopictus is now accelerating the situation through gradual adaptation to human surroundings. Global destabilization and gradual climatic shift with rising in temperature have significantly expanded the geographic range of these species These versatile vectors also host Chikungunya, Zika, and yellow fever virus. Biggest challenge faced by endemic countries now is upsurge in co-infection reported with multiple serotypes and virus co-circulation. To foster vector control interventions and mitigate disease burden, there is surge for knowledge on vector susceptibility and viral tolerance in response to multiple infections. To address our understanding on transmission dynamics and reproductive fitness, both the vectors were exposed to single and dual combinations of all four dengue serotypes by artificial feeding and followed up to third generation. Artificial feeding observed significant difference in feeding rate for both the species where A.albopictus was poor artificial feeder (35-50%) compared to A.aegypti (95-97%) Robust sequential screening of viral antigen in mosquitoes was followed by Dengue NS1 ELISA, RT-PCR and Quantitative PCR. To observe viral dissemination in different mosquito tissues Indirect immunofluorescence assay was performed. Result showed that both the vectors were infected initially with all dengue(1-4)serotypes and its co-infection (D1 and D2, D1 and D3, D1 and D4, D2 and D4) combinations. In case of DENV-2 there was significant difference in the peak titer observed at 16th day post infection. But when exposed to dual infections A.aegypti supported all combinations of virus where A.albopictus only continued single infections in successive days. There was a significant negative effect on the fecundity and fertility of both the vectors compared to control (PANOVA < 0.001). In case of dengue 2 infected mosquito, fecundity in parent generation was significantly higher (PBonferroni < 0.001) for A.albopicus compare to A.aegypti but there was a complete loss of fecundity from second to third generation for A.albopictus. It was observed that A.aegypti becomes infected with multiple serotypes frequently even at low viral titres compared to A.albopictus. Possible reason for this could be the presence of wolbachia infection in A.albopictus or mosquito innate immune response, small RNA interference etc. Based on the observations it could be anticipated that transovarial transmission may not be an important phenomenon for clinical disease outcome, due to the absence of viral positivity by third generation. Also, Dengue NS1 ELISA can be used for preliminary viral detection in mosquitoes as more than 90% of the samples were found positive compared to RT-PCR and viral load estimation.

Keywords: co-infection, dengue, reproductive fitness, viral quantification

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Authors: Sofia Papadimitriou

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INTRODUCTION: The differential diagnosis between acute viral and bacterial infections is an important cost-effectiveness parameter at the stage of the treatment process in order to achieve the maximum benefits in therapeutic intervention by combining the minimum cost to ensure the proper use of antibiotics.The discovery of sensitive and robust molecular diagnostic tests in response to the role of the host in infections has enhanced the accurate diagnosis and differentiation of infections. METHOD: The study used a sample of six independent blood samples (total=756) which are associated with human proteins-proteins, each of which at the transcription stage expresses a different response in the host network between viral and bacterial infections.Τhe individual blood samples are subjected to a sequence of computer filters that identify a gene panel corresponding to an autonomous diagnostic score. The data set and the correspondence of the gene panel to the diagnostic patents a new Bangalore -Viral Bacterial (BL-VB). FINDING: We use a biomarker based on the blood of 10 genes(Panel-VB) that are an important prognostic value for the detection of viruses from bacterial infections with a weighted average AUROC of 0.97(95% CL:0.96-0.99) in eleven independent samples (sets n=898). We discovered a base with a patient score (VB 10 ) according to the table, which is a significant diagnostic value with a weighted average of AUROC 0.94(95% CL: 0.91-0.98) in 2996 patient samples from 56 public sets of data from 19 different countries. We also studied VB 10 in a new cohort of South India (BL-VB,n=56) and found 97% accuracy in confirmed cases of viral and bacterial infections. We found that VB 10 (a)accurately identifies the type of infection even in unspecified cases negative to the culture (b) shows its clinical condition recovery and (c) applies to all age groups, covering a wide range of acute bacterial and viral infectious, including non-specific pathogens. We applied our VB 10 rating to publicly available COVID 19 data and found that our rating diagnosed viral infection in patient samples. RESULTS: Τhe results of the study showed the diagnostic power of the biomarker VB 10 as a diagnostic test for the accurate diagnosis of acute infections in recovery conditions. We look forward to helping you make clinical decisions about prescribing antibiotics and integrating them into your policies management of antibiotic stewardship efforts. CONCLUSIONS: Overall, we are developing a new property of the RNA-based biomarker and a new blood test to differentiate between viral and bacterial infections to assist a physician in designing the optimal treatment regimen to contribute to the proper use of antibiotics and reduce the burden on antimicrobial resistance, AMR.

Keywords: acute infections, antimicrobial resistance, biomarker, blood transcriptome, systems biology, classifier diagnostic score

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Authors: A. Gonzalez Aguna, J. M. Santamaria Garcia, J. L. Gomez Gonzalez, R. Barchino Plata, M. Fernandez Batalla, S. Herrero Jaen

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Background: Computer Science is a field that transcends other disciplines of knowledge because it allows to support all kinds of physical and mental tasks. Health centres have a greater number and complexity of technological devices and the population consume and demand services derived from technology. Also, nursing education plans have included competencies related to and, even, courses about new technologies are offered to health professionals. However, nurses still limit their performance to the use and evaluation of products previously built. Objective: Develop a teaching-learning methodology for acquiring skills on designing applications for care. Methodology: Blended learning teaching with a group of graduate nurses through official training within a Master's Degree. The study sample was selected by intentional sampling without exclusion criteria. The study covers from 2015 to 2017. The teaching sessions included a four-hour face-to-face class and between one and three tutorials. The assessment was carried out by written test consisting of the preparation of an IEEE 830 Standard Specification document where the subject chosen by the student had to be a problem in the area of care. Results: The sample is made up of 30 students: 10 men and 20 women. Nine students had a degree in nursing, 20 diploma in nursing and one had a degree in Computer Engineering. Two students had a degree in nursing specialty through residence and two in equivalent recognition by exceptional way. Except for the engineer, no subject had previously received training in this regard. All the sample enrolled in the course received the classroom teaching session, had access to the teaching material through a virtual area and maintained at least one tutoring. The maximum of tutorials were three with an hour in total. Among the material available for consultation was an example of a document drawn up based on the IEEE Standard with an issue not related to care. The test to measure competence was completed by the whole group and evaluated by a multidisciplinary teaching team of two computer engineers and two nurses. Engineers evaluated the correctness of the characteristics of the document and the degree of comprehension in the elaboration of the problem and solution elaborated nurses assessed the relevance of the chosen problem statement, the foundation, originality and correctness of the proposed solution and the validity of the application for clinical practice in care. The results were of an average grade of 8.1 over 10 points, a range between 6 and 10. The selected topic barely coincided among the students. Examples of care areas selected are care plans, family and community health, delivery care, administration and even robotics for care. Conclusion: The applied methodology of learning-teaching for the design of technologies demonstrates the success in the training of nursing professionals. The role of expert is essential to create applications that satisfy the needs of end users. Nursing has the possibility, the competence and the duty to participate in the process of construction of technological tools that are going to impact in care of people, family and community.

Keywords: care, learning, nursing, technology

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Authors: Catelyn Coyle, Helena Kwakwa

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Objective: As novel and better tolerated therapies become available, effective HCV testing and care models become increasingly necessary to not only identify individuals with active infection but also link them to HCV providers for medical evaluation and treatment. Our aim is to describe an effective HCV testing and linkage to care model piloted in a network of five community health centers located in Philadelphia, PA. Methods: In October 2012, National Nursing Centers Consortium piloted a routine opt-out HCV testing model in a network of community health centers, one of which treats HCV, HIV, and co-infected patients. Key aspects of the model were medical assistant initiated testing, the use of laboratory-based reflex test technology, and electronic medical record modifications to prompt, track, report and facilitate payment of test costs. Universal testing on all adult patients was implemented at health centers serving patients at high-risk for HCV. The other sites integrated high-risk based testing, where patients meeting one or more of the CDC testing recommendation risk factors or had a history of homelessness were eligible for HCV testing. Mid-course adjustments included the integration of dual HIV testing, development of a linkage to care coordinator position to facilitate the transition of HIV and/or HCV-positive patients from primary to specialist care, and the transition to universal HCV testing across all testing sites. Results: From October 2012 to June 2015, the health centers performed 7,730 HCV tests and identified 886 (11.5%) patients with a positive HCV-antibody test. Of those with positive HCV-antibody tests, 838 (94.6%) had an HCV-RNA confirmatory test and 590 (70.4%) progressed to current HCV infection (overall prevalence=7.6%); 524 (88.8%) received their RNA-positive test result; 429 (72.7%) were referred to an HCV care specialist and 271 (45.9%) were seen by the HCV care specialist. The best linkage to care results were seen at the test and treat the site, where of the 333 patients were current HCV infection, 175 (52.6%) were seen by an HCV care specialist. Of the patients with active HCV infection, 349 (59.2%) were unaware of their HCV-positive status at the time of diagnosis. Since the integration of dual HCV/HIV testing in September 2013, 9,506 HIV tests were performed, 85 (0.9%) patients had positive HIV tests, 81 (95.3%) received their confirmed HIV test result and 77 (90.6%) were linked to HIV care. Dual HCV/HIV testing increased the number of HCV tests performed by 362 between the 9 months preceding dual testing and first 9 months after dual testing integration, representing a 23.7% increment. Conclusion: Our HCV testing model shows that integrated routine testing and linkage to care is feasible and improved detection and linkage to care in a primary care setting. We found that prevalence of current HCV infection was higher than that seen in locally in Philadelphia and nationwide. Intensive linkage services can increase the number of patients who successfully navigate the HCV treatment cascade. The linkage to care coordinator position is an important position that acts as a trusted intermediary for patients being linked to care.

Keywords: HCV, routine testing, linkage to care, community health centers

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Authors: Uchenna Nkiruka Umeononihu, Adenike Kuku, Oludele Odekanyin, Olubunmi Babalola, Femi Agboola, Rapheal Okonji

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In this study, a lectin from the bulb of Dioscorea bulbifera was purified, characterised, and its acute and sub-acute toxicity was investigated with a view to evaluate its toxic effects in mice. The protein from the bulb was extracted by homogenising 50 g of the bulb in 500 ml of phosphate buffered saline (0.025 M) of pH 7.2, stirred for 3 hr, and centrifuged at the speed of 3000 rpm. Blood group and sugar specificity assays of the crude extract were determined. The lectin was purified in a two-step procedure- gel filtration on Sephadex G-75 and affinity chromatography on Sepharose 4-B arabinose. The degree of purity of the purified lectin was ascertained by SDS-polyacrylamide gel electrophoresis. Detection of covalently bound carbohydrate was carried out with Periodic Acid-Schiffs (PAS) reagent staining technique. Effects of temperature, pH, and EDTA on the lectin were carried out using standard methods. This was followed by acute toxicity studies via oral and subcutaneous routes using mice. The animals were monitored for mortality and signs of toxicity. The sub-acute toxicity studies were carried out using rats. Different concentrations of the lectin were administered twice daily for 5 days via the subcutaneous route. The animals were sacrificed on the sixth day; blood samples and liver tissues were collected. Biochemical assays (determination of total protein, direct bilirubin, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), catalase (CAT), and superoxide dismutase (SOD)) were carried out on the serum and liver homogenates. The collected organs (heart, liver, kidney, and spleen) were subjected to histopathological analysis. The results showed that lectin from the bulbs of Dioscorea bulbifera agglutinated non-specifically the erythrocytes of the human ABO system as well as rabbit erythrocytes. The haemagglutinating activity was strongly inhibited by arabinose and dulcitol with minimum inhibitory concentrations of 0.781 and 6.25, respectively. The lectin was purified to homogeneity with native and subunit molecular weights of 56,273 and 29,373 Daltons, respectively. The lectin was thermostable up to 30 0C and lost 25 %, 33.3 %, and 100 % of its heamagglutinating activity at 40°C, 50°C, and 60°C, respectively. The lectin was maximally active at pH 4 and 5 but lost its total activity at pH eight, while EDTA (10 mM) had no effect on its haemagglutinating activity. PAS reagent staining showed that the lectin was not a glycoprotein. The sub-acute studies on rats showed elevated levels of ALT, AST, serum bilirubin, total protein in serum and liver homogenates suggesting damage to liver and spleen. The study concluded that the aerial bulb of D. bulbifera lectin was non-specific in its heamagglutinating activity and dimeric in its structure. The lectin shared some physicochemical characteristics with lectins from other Dioscorecea species and was moderately toxic to the liver and spleen of treated animals.

Keywords: Dioscorea bulbifera, heamagglutinin, lectin, toxicity

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Authors: Hamdan Hamood Aldumaini, Amjad Hussein Meqdam, Shamsaldeen kassim Ali, Hamed Mohammed Al-Yousefi, Haron Ahmed Al-Badawi

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Background: Autism Spectrum Disorder (ASD) is a complex developmental challenge characterized by significant impairments in social interaction, communication, and behavioral patterns. Diagnosing ASD is challenging due to the lack of definitive medical tests, making early identification crucial. Therefore, increasing people's awareness about autism leads to early diagnosis and better prognosis. Objective: Our study aims to identify the initial symptoms prompting families to seek medical advice, determine the timeline between symptom onset and formal diagnosis, and explore methods for assessing the severity of ASD. Subjects and Methods: The study design employed was a descriptive cross-sectional design, which was suitable for the nature of the research. The data collection took place from March 5, 2022, to April 5, 2022, in Autism Rehabilitation Centers in Sana'a, Yemen. The study population consisted of all children who were diagnosed with autism and visited Autism rehabilitation centers in Sana'a city. The sample size was determined using Epi info version 7, and a total population of 587 autistic children attending the treatment was calculated, but only 250 children were included in this study (176 were male vs. 74 female). Result: In terms of sociability problems, it was found that a significant proportion of Yemeni children with autism experienced difficulties in this area. Specifically, 39.6% were classified as having severe sociability problems, while 28.4% were classified as having moderate issues. Sensory-cognitive awareness problems were also prevalent among the respondents, with 29.6% exhibiting severe difficulties in this domain. Health and physical problems were identified as significant concerns for Yemeni children with autism. The results indicated that 38.4% of the participants experienced severe health and physical issues. Identifying the first symptoms of autism is crucial for early detection and intervention. According to the study, speech delay was the most commonly observed first abnormality, reported by 71.3% of parents. Communication difficulties with others were the second most noticed abnormality, reported by 54.9% of parents. Repetitive movements were the third most commonly observed abnormality, reported by 18% of parents. Regarding the awareness among parents of ASD, our study showed that a significant portion (62%) of parents lack awareness about Autism Spectrum Disorder (ASD) and its causes. Surprisingly, a majority of these parents (over 80%) believe that autism is a curable condition. Additionally, more than half (51.2%) of the parents surveyed reported insufficient knowledge about medication options available to support therapy and rehabilitation for their autistic children.

Keywords: autism characteristics, rehabilitation centres, yemen, children

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Authors: Yifan Qiao, Huanying Sun, Shimeng Hao

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Objective: This study aims to investigate the therapeutic benefits of comprehensive street renovations and their individual components from a multisensory perspective, identifying key factors that enhance the multisensory experience in urban public spaces. Method: The study employed a combination of physiological measurements and subjective ratings to investigate the healing effects of street renovations from three sensory perspectives: visual, auditory (single soundscape vs. mixed soundscape), and olfactory (single scent vs. mixed scents). Forty university students (balanced gender) were recruited and randomly assigned to three independent groups to experience different stimuli: (1) Visual only group (N=14); (2) Visual and auditory group (N=13); (3) Visual, auditory, and olfactory group (N=13). Each group experienced three VR scenarios in sequence: Visual - current scenario; Auditory - single bird song (sparrow); Olfactory - single scent (bush). Visual - pavement and seating renovation scenario (adding bike lanes, shallow grass ditches, seats, changing ground pavement); Auditory - two bird songs (sparrow, blackbird); Olfactory - two scents (bush, grass). Visual - increased plant configuration scenario (peach tree, rose); Auditory - three bird songs (sparrow, blackbird, and blue-throated); Olfactory - three scents (bush, grass, rose, and peach tree). Participants wore devices to monitor physiological data (EEG, GSR, and HRV), used the Perceived Restorativeness Scale (PRS) to assess recovery effects, and a self-made sensory evaluation scale to evaluate indicators such as sensory pleasure and richness. Results: Physiological measurements indicated that renovated scenarios (pavement and seating renovation and increased plant configuration) had better relaxation effects. In the visual-only group, emotional healing increased with renovations, but this trend weakened when auditory elements were added, especially in the visual, auditory, and olfactory groups. Subjective evaluations of all sensory combinations showed a significant increase with renovation improvements. The sensory evaluation scale revealed that positive olfactory evaluations enhanced visual and auditory sensory ratings, and floral scents effectively countered the negative impacts of adverse auditory factors. Conclusion: Overall, renovated streets demonstrated greater restorative potential than before the renovation. The multisensory combination after renovation (visual, auditory, and olfactory) showed the highest recovery scores. Participants preferred visually biodiverse environments, which induced pleasure and a sense of safety. However, overly diverse auditory and olfactory stimuli could lead to sensory overload and discomfort. This study demonstrates that the healing effects of multisensory combinations are closely related to sensory pleasure, sensory coordination, and sensory overload, providing valuable insights for future street renovation designs and multisensory urban design strategies.

Keywords: multisensory integration, street renovation, urban landscape, sensory healing, visual enhancement

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Authors: Syed Asif Hassan, Tabrej Khan

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Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

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Authors: N. Naz, A. D. Domenico, M. N. Huda

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Soft Robotics is a rapidly growing multidisciplinary field where robots are fabricated using highly deformable materials motivated by bioinspired designs. The high dexterity and adaptability to the external environments during contact make soft robots ideal for applications such as gripping delicate objects, locomotion, and biomedical devices. The actuation system of soft robots mainly includes fluidic, tendon-driven, and smart material actuation. Among them, Soft Pneumatic Actuator, also known as SPA, remains the most popular choice due to its flexibility, safety, easy implementation, and cost-effectiveness. However, at present, most of the fabrication of SPA is still based on traditional molding and casting techniques where the mold is 3d printed into which silicone rubber is cast and consolidated. This conventional method is time-consuming and involves intensive manual labour with the limitation of repeatability and accuracy in design. Recent advancements in direct 3d printing of different soft materials can significantly reduce the repetitive manual task with an ability to fabricate complex geometries and multicomponent designs in a single manufacturing step. The aim of this research work is to design and analyse the Soft Pneumatic Actuator (SPA) utilizing both conventional casting and modern direct 3d printing technologies. The mold of the SPA for traditional casting is 3d printed using fused deposition modeling (FDM) with the polylactic acid (PLA) thermoplastic wire. Hyperelastic soft materials such as Ecoflex-0030/0050 are cast into the mold and consolidated using a lab oven. The bending behaviour is observed experimentally with different pressures of air compressor to ensure uniform bending without any failure. For direct 3D-printing of SPA fused deposition modeling (FDM) with thermoplastic polyurethane (TPU) and stereolithography (SLA) with an elastic resin are used. The actuator is modeled using the finite element method (FEM) to analyse the nonlinear bending behaviour, stress concentration and strain distribution of different hyperelastic materials after pressurization. FEM analysis is carried out using Ansys Workbench software with a Yeon-2nd order hyperelastic material model. FEM includes long-shape deformation, contact between surfaces, and gravity influences. For mesh generation, quadratic tetrahedron, hybrid, and constant pressure mesh are used. SPA is connected to a baseplate that is in connection with the air compressor. A fixed boundary is applied on the baseplate, and static pressure is applied orthogonally to all surfaces of the internal chambers and channels with a closed continuum model. The simulated results from FEM are compared with the experimental results. The experiments are performed in a laboratory set-up where the developed SPA is connected to a compressed air source with a pressure gauge. A comparison study based on performance analysis is done between FDM and SLA printed SPA with the molded counterparts. Furthermore, the molded and 3d printed SPA has been used to develop a three-finger soft pneumatic gripper and has been tested for handling delicate objects.

Keywords: finite element method, fused deposition modeling, hyperelastic, soft pneumatic actuator

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Authors: Vladimir Smirnov, Roman Tominov, Vadim Avilov, Oleg Ageev

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The creation of a new generation micro- and nanoelectronics elements opens up unlimited possibilities for electronic devices parameters improving, as well as developing neuromorphic computing systems. Interest in the latter is growing up every year, which is explained by the need to solve problems related to the unstructured classification of data, the construction of self-adaptive systems, and pattern recognition. However, for its technical implementation, it is necessary to fulfill a number of conditions for the basic parameters of electronic memory, such as the presence of non-volatility, the presence of multi-bitness, high integration density, and low power consumption. Several types of memory are presented in the electronics industry (MRAM, FeRAM, PRAM, ReRAM), among which non-volatile resistive memory (ReRAM) is especially distinguished due to the presence of multi-bit property, which is necessary for neuromorphic systems manufacturing. ReRAM is based on the effect of resistive switching – a change in the resistance of the oxide film between low-resistance state (LRS) and high-resistance state (HRS) under an applied electric field. One of the methods for the technical implementation of neuromorphic systems is cross-bar structures, which are ReRAM cells, interconnected by cross data buses. Such a structure imitates the architecture of the biological brain, which contains a low power computing elements - neurons, connected by special channels - synapses. The choice of the ReRAM oxide film material is an important task that determines the characteristics of the future neuromorphic system. An analysis of literature showed that many metal oxides (TiO2, ZnO, NiO, ZrO2, HfO2) have a resistive switching effect. It is worth noting that the manufacture of nanocomposites based on these materials allows highlighting the advantages and hiding the disadvantages of each material. Therefore, as a basis for the neuromorphic structures manufacturing, it was decided to use ZnₓTiᵧHfzOᵢ nanocomposite. It is also worth noting that the ZnₓTiᵧHfzOᵢ nanocomposite does not need an electroforming, which degrades the parameters of the formed ReRAM elements. Currently, this material is not well studied, therefore, the study of the effect of resistive switching in forming-free ZnₓTiᵧHfzOᵢ nanocomposite is an important task and the goal of this work. Forming-free nanocomposite ZnₓTiᵧHfzOᵢ thin film was grown by pulsed laser deposition (Pioneer 180, Neocera Co., USA) on the SiO2/TiN (40 nm) substrate. Electrical measurements were carried out using a semiconductor characterization system (Keithley 4200-SCS, USA) with W probes. During measurements, TiN film was grounded. The analysis of the obtained current-voltage characteristics showed a resistive switching from HRS to LRS resistance states at +1.87±0.12 V, and from LRS to HRS at -2.71±0.28 V. Endurance test shown that HRS was 283.21±32.12 kΩ, LRS was 1.32±0.21 kΩ during 100 measurements. It was shown that HRS/LRS ratio was about 214.55 at reading voltage of 0.6 V. The results can be useful for forming-free nanocomposite ZnₓTiᵧHfzOᵢ films in neuromorphic systems manufacturing. This work was supported by RFBR, according to the research project № 19-29-03041 mk. The results were obtained using the equipment of the Research and Education Center «Nanotechnologies» of Southern Federal University.

Keywords: nanotechnology, nanocomposites, neuromorphic systems, RRAM, pulsed laser deposition, resistive switching effect

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Authors: Wu Liching

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Aim This case aims to discuss the pathogenesis, clinical manifestations and medical treatment of strokes caused by mitochondrial gene mutations. Methods Diagnosis of ischemic stroke caused by mitochondrial gene defect by means of "next-generation sequencing mitochondrial DNA gene variation detection", imaging examination, neurological examination, and medical history; this study took samples from the neurology ward of a medical center in northern Taiwan cases diagnosed with acute cerebral infarction as the research objects. Result This case is a 49-year-old married woman with a rare disease, mitochondrial gene mutation inducing ischemic stroke. She has severe hearing impairment and needs to use hearing aids, and has a history of diabetes. During the patient’s hospitalization, the blood test showed that serum Lactate: 7.72 mmol/L, Lactate (CSF) 5.9 mmol/L. Through the collection of relevant medical history, neurological evaluation showed changes in consciousness and cognition, slow response in language expression, and brain magnetic resonance imaging examination showed subacute bilateral temporal lobe infarction, which was an atypical type of stroke. The lineage DNA gene has m.3243A>G known pathogenic mutation point, and its heteroplasmic level is 24.6%. This pathogenic point is located in MITOMAP and recorded as Mitochondrial Encephalopathy, Lactic Acidosis, and Stroke-like episodes (MELAS) , Leigh Syndrome and other disease-related pathogenic loci, this mutation is located in ClinVar and recorded as Pathogenic (dbSNP: rs199474657), so it is diagnosed as a case of stroke caused by a rare disease mitochondrial gene mutation. After medical treatment, there was no more seizure during hospitalization. After interventional rehabilitation, the patient's limb weakness, poor language function, and cognitive impairment have all improved significantly. Conclusion Mitochondrial disorders can also be associated with abnormalities in psychological, neurological, cerebral cortical function, and autonomic functions, as well as problems with internal medical diseases. Therefore, the differential diagnoses cover a wide range and are not easy to be diagnosed. After neurological evaluation, medical history collection, imaging and rare disease serological examination, atypical ischemic stroke caused by rare mitochondrial gene mutation was diagnosed. We hope that through this case, the diagnosis of rare disease mitochondrial gene variation leading to cerebral infarction will be more familiar to clinical medical staff, and this case report may help to improve the clinical diagnosis and treatment for patients with similar clinical symptoms in the future.

Keywords: acute stroke, MELAS, lactic acidosis, mitochondrial disorders

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Authors: Kari Björn

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Introduction of games has expanded the application area of computer-aided learning tools to wide variety of age groups of learners. Serious games engage the learners into a real-world -type of simulation and potentially enrich the learning experience. Institutional background of a Bachelor’s level engineering program in Information and Communication Technology is introduced, with detailed focus on one of its majors, Health Technology. As part of a Customer Oriented Software Application thematic semester, one particular course of “eHealth Business and Solutions” is described and reflected in a gamified framework. Learning a consistent view into vast literature of business management, strategies, marketing and finance in a very limited time enforces selection of topics relevant to the industry. Health Technology is a novel and growing industry with a growing sector in consumer wearable devices and homecare applications. The business sector is attracting new entrepreneurs and impatient investor funds. From engineering education point of view the sector is driven by miniaturizing electronics, sensors and wireless applications. However, the market is highly consumer-driven and usability, safety and data integrity requirements are extremely high. When the same technology is used in analysis or treatment of patients, very strict regulatory measures are enforced. The paper introduces a course structure using gamification as a tool to learn the most essential in a new market: customer value proposition design, followed by a market entry game. Students analyze the existing market size and pricing structure of eHealth web-service market and enter the market as a steering group of their company, competing against the legacy players and with each other. The market is growing but has its rules of demand and supply balance. New products can be developed with an R&D-investment, and targeted to market with unique quality- and price-combinations. Product cost structure can be improved by investing to enhanced production capacity. Investments can be funded optionally by foreign capital. Students make management decisions and face the dynamics of the market competition in form of income statement and balance sheet after each decision cycle. The focus of the learning outcome is to understand customer value creation to be the source of cash flow. The benefit of gamification is to enrich the learning experience on structure and meaning of financial statements. The paper describes the gamification approach and discusses outcomes after two course implementations. Along the case description of learning challenges, some unexpected misconceptions are noted. Improvements of the game or the semi-gamified teaching pedagogy are discussed. The case description serves as an additional support to new game coordinator, as well as helps to improve the method. Overall, the gamified approach has helped to engage engineering student to business studies in an energizing way.

Keywords: engineering education, integrated curriculum, learning experience, learning outcomes

Procedia PDF Downloads 223

Authors: John Doe

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This paper presents the research project “Escape Through Culture”, which is co-funded by the European Union and national resources through the Operational Programme “Competitiveness, Entrepreneurship and Innovation” 2014-2020 and the Single RTDI State Aid Action "RESEARCH - CREATE - INNOVATE". The project implementation is assumed by three partners, (1) the Computer Technology Institute and Press "Diophantus" (CTI), experienced with the design and implementation of serious games, natural language processing and ICT in education, (2) the Laboratory of Environmental Communication and Audiovisual Documentation (LECAD), part of the University of Thessaly, Department of Architecture, which is experienced with the study of creative transformation and reframing of the urban and environmental multimodal experiences through the use of AR and VR technologies, and (3) “Apoplou”, an IT Company with experience in the implementation of interactive digital applications. The research project proposes the design of innovative infrastructure of digital educational escape games for mobile devices and computers, with the use of Virtual Reality and Augmented Reality for the promotion of Greek cultural heritage in Greece and abroad. In particular, the project advocates the combination of Greek cultural heritage and literature, digital technologies advancements and the implementation of innovative gamifying practices. The cultural experience of the players will take place in 3 layers: (1) In space: the digital games produced are going to utilize the dual character of the space as a cultural landscape (the real space - landscape but also the space - landscape as presented with the technologies of augmented reality and virtual reality). (2) In literary texts: the selected texts of Greek writers will support the sense of place and the multi-sensory involvement of the user, through the context of space-time, language and cultural characteristics. (3) In the philosophy of the "escape game" tool: whether played in a computer environment, indoors or outdoors, the spatial experience is one of the key components of escape games. The innovation of the project lies both in the junction of Augmented/Virtual Reality with the promotion of cultural points of interest, as well as in the interactive, gamified practices of literary texts. The digital escape game infrastructure will be highly interactive, integrating the projection of Greek landscape cultural elements and digital literary text analysis, supporting the creation of escape games, establishing and highlighting new playful ways of experiencing iconic cultural places, such as Elefsina, Skiathos etc. The literary texts’ content will relate to specific elements of the Greek cultural heritage depicted by prominent Greek writers and poets. The majority of the texts will originate from Greek educational content available in digital libraries and repositories developed and maintained by CTI. The escape games produced will be available for use during educational field trips, thematic tourism holidays, etc. In this paper, the methodology adopted for infrastructure development will be presented. The research is based on theories of place, gamification, gaming development, making use of corpus linguistics concepts and digital humanities practices for the compilation and the analysis of literary texts.

Keywords: escape games, cultural landscapes, gamification, digital humanities, literature

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Authors: K. Power, M. White, B. Dunleavey, E. Comerford, C. Doherty, N. Delanty, R. Corbridge, M. Fitzsimons

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Introduction: Providing people with access to their own healthcare information and engaging them as co-authors of their health record can promote better transparency, trust, and inclusivity in the healthcare system. With the advent of electronic health records, there is a move towards involving patients as partners in their healthcare by providing them with access to their own health data via electronic patient portals (ePortal). For example, a recently developed ePortal to the Irish National Epilepsy Electronic Patient Record (EPR) provides access to summary medical records, tools for Patient Reported Outcomes (PROM), health goal-setting and preparation for clinical appointments. Aim: To determine what people with epilepsy (their families/carers) value about the Irish epilepsy ePortal. Methods: A socio-technical process was employed recruiting 30 families of people with epilepsy who also have an intellectual disability (ID). Family members who are a care partner of the person with epilepsy (PWE) were invited to co-design, develop and implement the ePortal. Family members engaged in usability and utility testing which involved a face to face meeting to learn about the ePortal, register for a user account and evaluate its structure and content. Family members were instructed to login to the portal on at least two separate occasions following the meeting and to complete a self-report evaluation tool during this time. The evaluation tool, based on a Usability Questionnaire (Lewis, 1993), consists of a short assessment of comfort using technology, instructions for using the ePortal and some tasks to complete. Tasks included validating summary record details, assessing ePortal ease of use, evaluation of information presented. Participants were asked for suggestions on how to improve the portal and make it more applicable to PWE who also have an ID. Results: Family members responded positively to the ePortal and valued the ability to share information between clinicians and care partners; use the ePortal as a passport between different healthcare settings (e.g., primary care to hospital). In the context of elderly parents of PWE, the ePortal is valued as a tool for supporting shared care between family members. Participants welcomed the facility to log lists of questions and goals to discuss with the clinician at the next clinical appointment as a means of improving quality of care. Participants also suggested further enhancements to the ePortal such as access to clinic letters which can provide an aide memoir in terms of the careplan agreed with the clinical team. For example, through the ePortal, people could see what investigations or therapies are scheduled. Conclusion: The Epilepsy Patient Portal is accessible via a range of devices such as smartphones and tablets. ePortals have the potential to help personalise care, improve patient involvement in clinical decision making, engage them as quality and safety partners, and help clinicians be more responsive to patient needs. Acknowledgement: The epilepsy ePortal project is part of PISCES, a Lighthouse Project funded by eHealth Ireland and HSE to help build an understanding of the benefits of eHealth technologies in the Irish Healthcare System.

Keywords: electronic patient portal, electronic patient record, epilepsy, intellectual disability, usability testing

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Authors: Mishak Rahul, Naveen Kumar, Bharath Kumar

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Conceived as a high-end engine to revolutionise sustainable agri-food production, the intelligent crop circle (ICC) aims to incorporate the Internet of Things (IoT), blockchain technology and artificial intelligence (AI) to bolster resource efficiency and prevent waste, increase the volume of production and bring about sustainable solutions with long-term ecosystem conservation as the guiding principle. The operating principle of the ICC relies on bringing together multidisciplinary bottom-up collaborations between producers, researchers and consumers. Key elements of the framework include IoT-based smart sensors for sensing soil moisture, temperature, humidity, nutrient and air quality, which provide short-interval and timely data; blockchain technology for data storage on a private chain, which maintains data integrity, traceability and transparency; and AI-based predictive analysis, which actively predicts resource utilisation, plant growth and environment. This data and AI insights are built into the ICC platform, which uses the resulting DSS (Decision Support System) outlined as help in decision making, delivered through an easy-touse mobile app or web-based interface. Farmers are assumed to use such a decision-making aid behind the power of the logic informed by the data pool. Building on existing data available in the farm management systems, the ICC platform is easily interoperable with other IoT devices. ICC facilitates connections and information sharing in real-time between users, including farmers, researchers and industrial partners, enabling them to cooperate in farming innovation and knowledge exchange. Moreover, ICC supports sustainable practice in agriculture by integrating gamification techniques to stimulate farm adopters, deploying VR technologies to model and visualise 3D farm environments and farm conditions, framing the field scenarios using VR headsets and Real-Time 3D engines, and leveraging edge technologies to facilitate secure and fast communication and collaboration between users involved. And through allowing blockchain-based marketplaces, ICC offers traceability from farm to fork – that is: from producer to consumer. It empowers informed decision-making through tailor-made recommendations generated by means of AI-driven analysis and technology democratisation, enabling small-scale and resource-limited farmers to get their voice heard. It connects with traditional knowledge, brings together multi-stakeholder interactions as well as establishes a participatory ecosystem to incentivise continuous growth and development towards more sustainable agro-ecological food systems. This integrated approach leverages the power of emerging technologies to provide sustainable solutions for a resilient food system, ensuring sustainable agriculture worldwide.

Keywords: blockchain, internet of things, artificial intelligence, decision support system, virtual reality, gamification, traceability, sustainable agriculture

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Authors: Joana Pimenta, Lorena Coelho, José Silva, Vanessa Miranda, Jorge Laranjeira, Rui Soares

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In this paper, the results of R&D on an innovative food package for increased shelf-life are presented. SAP4MA aims at the development of a printed active device that enables smart packaging solutions for food preservation, targeting the extension of the shelf-life of the packed food through the controlled release of active natural antioxidant agents at the onset of the food degradation process. To do so, SAP4MA focuses on the development of active devices such as printed heaters and batteries/supercapacitors in a label format to be integrated on packaging lids during its injection molding process, promoting the passive release of natural antioxidants after the product is packed, during transportation and in the shelves, and actively when the end-user activates the package, just prior to consuming the product at home. When the active device present on the lid is activated, the release of the natural antioxidants embedded in the inner layer of the packaging lid in direct contact with the headspace atmosphere of the food package starts. This approach is based on the use of active functional coatings composed of nano encapsulated active agents (natural antioxidants species) in the prevention of the oxidation of lipid compounds in food by agents such as oxygen. Thus keeping the product quality during the shelf-life, not only when the user opens the packaging, but also during the period from food packaging up until the purchase by the consumer. The active systems that make up the printed smart label, heating circuit, and battery were developed using screen-printing technology. These systems must operate under the working conditions associated with this application. The printed heating circuit was studied using three different substrates and two different conductive inks. Inks were selected, taking into consideration that the printed circuits will be subjected to high pressures and temperatures during the injection molding process. The circuit must reach a homogeneous temperature of 40ºC in the entire area of the lid of the food tub, promoting a gradual and controlled release of the antioxidant agents. In addition, the circuit design involves a high level of study in order to guarantee maximum performance after the injection process and meet the specifications required by the control electronics component. Furthermore, to characterize the different heating circuits, the electrical resistance promoted by the conductive ink and the circuit design, as well as the thermal behavior of printed circuits on different substrates, were evaluated. In the injection molding process, the serpentine-shaped design developed for the heating circuit was able to resolve the issues connected to the injection point; in addition, the materials used in the support and printing had high mechanical resistance against the pressure and temperature inherent to the injection process. Acknowledgment: This research has been carried out within the Project “Smart and Active Packing for Margarine Product” (SAP4MA) running under the EURIPIDES Program being co-financed by COMPETE 2020 – the Operational Programme for Competitiveness and Internationalization and under Portugal 2020 through the European Regional Development Fund (ERDF).

Keywords: smart package, printed heat circuits, printed batteries, flexible and printed electronic

Procedia PDF Downloads 87

Authors: Swapnil Kumar Singh

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Gamma-ray bursts (GRB's), short and intense pulses of low-energy γ rays, have fascinated astronomers and astrophysicists since their unexpected discovery in the late sixties. GRB'sare accompanied by long-lasting afterglows, and they are associated with core-collapse supernovae. The detection of delayed emission in X-ray, optical, and radio wavelength, or "afterglow," following a γ-ray burst can be described as the emission of a relativistic shell decelerating upon collision with the interstellar medium. While it is fair to say that there is strong diversity amongst the afterglow population, probably reflecting diversity in the energy, luminosity, shock efficiency, baryon loading, progenitor properties, circumstellar medium, and more, the afterglows of GRBs do appear more similar than the bursts themselves, and it is possible to identify common features within afterglows that lead to some canonical expectations. After an initial flash of gamma rays, a longer-lived "afterglow" is usually emitted at longer wavelengths (X-ray, ultraviolet, optical, infrared, microwave, and radio). It is a slowly fading emission at longer wavelengths created by collisions between the burst ejecta and interstellar gas. In X-ray wavelengths, the GRB afterglow fades quickly at first, then transitions to a less-steep drop-off (it does other stuff after that, but we'll ignore that for now). During these early phases, the X-ray afterglow has a spectrum that looks like a power law: flux F∝ E^β, where E is energy and beta is some number called the spectral index. This kind of spectrum is characteristic of synchrotron emission, which is produced when charged particles spiral around magnetic field lines at close to the speed of light. In addition to the outgoing forward shock that ploughs into the interstellar medium, there is also a so-called reverse shock, which propagates backward through the ejecta. In many ways," reverse" shock can be misleading; this shock is still moving outward from the restframe of the star at relativistic velocity but is ploughing backward through the ejecta in their frame and is slowing the expansion. This reverse shock can be dynamically important, as it can carry comparable energy to the forward shock. The early phases of the GRB afterglow still provide a good description even if the GRB is highly collimated since the individual emitting regions of the outflow are not in causal contact at large angles and so behave as though they are expanding isotropically. The majority of afterglows, at times typically observed, fall in the slow cooling regime, and the cooling break lies between the optical and the X-ray. Numerous observations support this broad picture for afterglows in the spectral energy distribution of the afterglow of the very bright GRB. The bluer light (optical and X-ray) appears to follow a typical synchrotron forward shock expectation (note that the apparent features in the X-ray and optical spectrum are due to the presence of dust within the host galaxy). We need more research in GRB and Particle Physics in order to unfold the mysteries of afterglow.

Keywords: GRB, synchrotron, X-ray, isotropic energy

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Authors: Lalit Ahuja, Nancy Das, Yashas Shetty

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LED lighting has been increasingly adopted for vehicles in both domestic and foreign automotive markets. Although this miniaturized technology gives the best light output, low energy consumption, and cost-efficient solutions for driving, the same is the need of the hour. In this paper, we present a methodology for driving the highest class two-wheeler headlamp with regulator and rectifier (RR) output. Unlike usual LED headlamps, which are driven by a battery, regulator, and rectifier (RR) driven, a low-cost and highly efficient LED Driver Module (LDM) is proposed. The positive half of magneto output is regulated and used to charge batteries used for various peripherals. While conventionally, the negative half was used for operating bulb-based exterior lamps. But with advancements in LED-based headlamps, which are driven by a battery, this negative half pulse remained unused in most of the vehicles. Our system uses negative half-wave rectified DC output from RR to provide constant light output at all RPMs of the vehicle. With the negative rectified DC output of RR, we have the advantage of pulsating DC input which periodically goes to zero, thus helping us to generate a constant DC output equivalent to the required LED load, and with a change in RPM, additional active thermal bypass circuit help us to maintain the efficiency and thermal rise. The methodology uses the negative half wave output of the RR along with a linear constant current driver with significantly higher efficiency. Although RR output has varied frequency and duty cycles at different engine RPMs, the driver is designed such that it provides constant current to LEDs with minimal ripple. In LED Headlamps, a DC-DC switching regulator is usually used, which is usually bulky. But with linear regulators, we’re eliminating bulky components and improving the form factor. Hence, this is both cost-efficient and compact. Presently, output ripple-free amplitude drivers with fewer components and less complexity are limited to lower-power LED Lamps. The focus of current high-efficiency research is often on high LED power applications. This paper presents a method of driving LED load at both High Beam and Low Beam using the negative half wave rectified pulsating DC from RR with minimum components, maintaining high efficiency within the thermal limitations. Linear regulators are significantly inefficient, with efficiencies typically about 40% and reaching as low as 14%. This leads to poor thermal performance. Although they don’t require complex and bulky circuitry, powering high-power devices is difficult to realise with the same. But with the input being negative half wave rectified pulsating DC, this efficiency can be improved as this helps us to generate constant DC output equivalent to LED load minimising the voltage drop on the linear regulator. Hence, losses are significantly reduced, and efficiency as high as 75% is achieved. With a change in RPM, DC voltage increases, which can be managed by active thermal bypass circuitry, thus resulting in better thermal performance. Hence, the use of bulky and expensive heat sinks can be avoided. Hence, the methodology to utilize the unused negative pulsating DC output of RR to optimize the utilization of RR output power and provide a cost-efficient solution as compared to costly DC-DC drivers.

Keywords: class D LED headlamp, regulator and rectifier, pulsating DC, low cost and highly efficient, LED driver module

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Authors: Panagiotis Gkekas, Christos Sougles, Dionysios Kehagias, Dimitrios Tzovaras

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This paper presents the architecture of the “Intelligent cooperative integrated system for road safety and road infrastructure maintenance towards 2020” (ODOS2020) advanced infrastructure, which implements a number of cooperative ITS applications based on Internet of Things and Infrastructure-to-Vehicle (V2I) technologies with the purpose to enhance the active road safety level of vehicles through the provision of a fully automated V2I environment. The primary objective of the ODOS2020 project is to contribute to increased road safety but also to the optimization of time for maintenance of road infrastructure. The integrated technological solution presented in this paper addresses all types of vehicles and requires minimum vehicle equipment. Thus, the ODOS2020 comprises a low-cost solution, which is one of its main benefits. The system architecture includes an integrated notification system to transmit personalized information on road, traffic, and environmental conditions, in order for the drivers to receive real-time and reliable alerts concerning upcoming critical situations. The latter include potential dangers on the road, such as obstacles or road works ahead, extreme environmental conditions, etc., but also informative messages, such as information on upcoming tolls and their charging policies. At the core of the system architecture lies an integrated sensorial network embedded in special road infrastructures (strips) that constantly collect and transmit wirelessly information about passing vehicles’ identification, type, speed, moving direction and other traffic information in combination with environmental conditions and road wear monitoring and predictive maintenance data. Data collected from sensors is transmitted by roadside infrastructure, which supports a variety of communication technologies such as ITS-G5 (IEEE-802.11p) wireless network and Internet connectivity through cellular networks (3G, LTE). All information could be forwarded to both vehicles and Traffic Management Centers (TMC) operators, either directly through the ITS-G5 network, or to smart devices with Internet connectivity, through cloud-based services. Therefore, through its functionality, the system could send personalized notifications/information/warnings and recommendations for upcoming events to both road users and TMC operators. In the course of the ODOS2020 project pilot operation has been conducted to allow drivers of both C-ITS equipped and non-equipped vehicles to experience the provided added value services. For non-equipped vehicles, the provided information is transmitted to a smartphone application. Finally, the ODOS2020 system and infrastructure is appropriate for installation on both urban, rural, and highway environments. The paper presents the various parts of the system architecture and concludes by outlining the various challenges that had to be overcome during its design, development, and deployment in a real operational environment. Acknowledgments: Work presented in this paper was co-financed by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation (call RESEARCH–CREATE–INNOVATE) under contract no. Τ1EDK-03081 (project ODOS2020).

Keywords: infrastructure to vehicle, intelligent transportation systems, internet of things, road safety

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Authors: Natia Jalagonia, Tinatin Kuchukhidze

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Polymer electrolytes (PE) play an important part in electrochemical devices such as batteries and fuel cells. To achieve optimal performance, the PE must maintain a high ionic conductivity and mechanical stability at both high and low relative humidity. The polymer electrolyte also needs to have excellent chemical stability for long and robustness. According to the prevailing theory, ionic conduction in polymer electrolytes is facilitated by the large-scale segmental motion of the polymer backbone, and primarily occurs in the amorphous regions of the polymer electrolyte. Crystallinity restricts polymer backbone segmental motion and significantly reduces conductivity. Consequently, polymer electrolytes with high conductivity at room temperature have been sought through polymers which have highly flexible backbones and have largely amorphous morphology. The interest in polymer electrolytes was increased also by potential applications of solid polymer electrolytes in high energy density solid state batteries, gas sensors and electrochromic windows. Conductivity of 10-3 S/cm is commonly regarded as a necessary minimum value for practical applications in batteries. At present, polyethylene oxide (PEO)-based systems are most thoroughly investigated, reaching room temperature conductivities of 10-7 S/cm in some cross-linked salt in polymer systems based on amorphous PEO-polypropylene oxide copolymers.. It is widely accepted that amorphous polymers with low glass transition temperatures Tg and a high segmental mobility are important prerequisites for high ionic conductivities. Another necessary condition for high ionic conductivity is a high salt solubility in the polymer, which is most often achieved by donors such as ether oxygen or imide groups on the main chain or on the side groups of the PE. It is well established also that lithium ion coordination takes place predominantly in the amorphous domain, and that the segmental mobility of the polymer is an important factor in determining the ionic mobility. Great attention was pointed to PEO-based amorphous electrolyte obtained by synthesis of comb-like polymers, by attaching short ethylene oxide unit sequences to an existing amorphous polymer backbone. The aim of presented work is to obtain of solid polymer electrolyte membranes using PMHS as a matrix. For this purpose the hydrosilylation reactions of α,ω-bis(trimethylsiloxy)methyl¬hydrosiloxane with allyl triethylene-glycol mo¬nomethyl ether and vinyltriethoxysilane at 1:28:7 ratio of initial com¬pounds in the presence of Karstedt’s catalyst, platinum hydrochloric acid (0.1 M solution in THF) and platinum on the carbon catalyst in 50% solution of anhydrous toluene have been studied. The synthesized olygomers are vitreous liquid products, which are well soluble in organic solvents with specific viscosity ηsp ≈ 0.05 - 0.06. The synthesized olygomers were analysed with FTIR, 1H, 13C, 29Si NMR spectroscopy. Synthesized polysiloxanes were investigated with wide-angle X-ray, gel-permeation chromatography, and DSC analyses. Via sol-gel processes of doped with lithium trifluoromethylsulfonate (triflate) or lithium bis¬(trifluoromethylsulfonyl)¬imide polymer systems solid polymer electrolyte membranes have been obtained. The dependence of ionic conductivity as a function of temperature and salt concentration was investigated and the activation energies of conductivity for all obtained compounds are calculated

Keywords: synthesis, PMHS, membrane, electrolyte

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Authors: Ipsita Biswas, Arnab Sarkar, Ashikur Rahaman, Gopeswar Mukherjee, Subhrangsu Chatterjee, Shamee Bhattacharjee, Deba Prasad Mandal

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One of the major reasons for the high mortality rate of lung cancer is the substantial delays in disease detection at late metastatic stages. It is of utmost importance to understand the detailed molecular signaling and detect the molecular markers that can be used for the early diagnosis of cancer. Several studies explored the emerging roles of long noncoding RNAs (lncRNAs) in various cancers as well as lung cancer. A long non-coding RNA LINC00273 was recently discovered to promote cancer cell migration and invasion, and its positive correlation with the pathological stages of metastasis may prove it to be a potential target for inhibiting cancer cell metastasis. Comparing real-time expression of LINC00273 in various human clinical cancer tissue samples with normal tissue samples revealed significantly higher expression in cancer tissues. This long intergenic noncoding RNA was found to be highly expressed in human liver tumor-initiating cells, human gastric adenocarcinoma AGS cell line, as well as human non-small cell lung cancer A549 cell line. SiRNA and shRNA-induced knockdown of LINC00273 in both in vitro and in vivo nude mice significantly subsided AGS and A549 cancer cell migration and invasion. LINC00273 knockdown also reduced TGF-β induced SNAIL, SLUG, VIMENTIN, ZEB1 expression, and metastasis in A549 cells. Plenty of reports have suggested the role of microRNAs of the miR200 family in reversing epithelial to mesenchymal transition (EMT) by inhibiting ZEB transcription factors. In this study, hsa-miR-200a-3p was predicted via IntaRNA-Freiburg RNA tools to be a potential target of LINC00273 with a negative free binding energy of −8.793 kcal/mol, and this interaction was verified as a confirmed target of LINC00273 by RNA pulldown, real-time PCR and luciferase assay. Mechanistically, LINC00273 accelerated TGF-β induced EMT by sponging hsa-miR-200a-3p which in turn liberated ZEB1 and promoted prometastatic functions in A549 cells in vitro as verified by real-time PCR and western blotting. The similar expression patterns of these EMT regulatory pathway molecules, viz. LINC00273, hsa-miR-200a-3p, ZEB1 and TGF-β, were also detected in various clinical samples like breast cancer tissues, oral cancer tissues, lung cancer tissues, etc. Overall, this LINC00273 mediated EMT regulatory signaling can serve as a potential therapeutic target for the prevention of lung cancer metastasis.

Keywords: epithelial to mesenchymal transition, long noncoding RNA, microRNA, non-small-cell lung carcinoma

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Authors: B. S. Muddukrishna, Karthik Aithal, Aravind Pai

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Introduction: Preparation of binary cocrystals of Etraverine (ETR) by using Tartaric Acid (TAR) as a conformer was the main focus of this study. Etravirine is a Class IV drug, as per the BCS classification system. Methods: Cocrystals were prepared by slow evaporation technique. A mixture of total 500mg of ETR: TAR was weighed in molar ratios of 1:1 (371.72mg of ETR and 128.27mg of TAR). Saturated solution of Etravirine was prepared in Acetone: Methanol (50:50) mixture in which tartaric acid is dissolved by sonication and then this solution was stirred using a magnetic stirrer until the solvent got evaporated. Shimadzu FTIR – 8300 system was used to acquire the FTIR spectra of the cocrystals prepared. Shimadzu thermal analyzer was used to achieve DSC measurements. X-ray diffractometer was used to obtain the X-ray powder diffraction pattern. Shake flask method was used to determine the equilibrium dynamic solubility of pure, physical mixture and cocrystals of ETR. USP buffer (pH 6.8) containing 1% of Tween 80 was used as the medium. The pure, physical mixture and the optimized cocrystal of ETR were accurately weighed sufficient to maintain the sink condition and were filled in hard gelatine capsules (size 4). Electrolab-Tablet Dissolution tester using basket apparatus at a rotational speed of 50 rpm and USP phosphate buffer (900 mL, pH = 6.8, 37 ˚C) + 1% Tween80 as a media, was used to carry out dissolution. Shimadzu LC-10 series chromatographic system was used to perform the analysis with PDA detector. An Hypersil BDS C18 (150mm ×4.6 mm ×5 µm) column was used for separation with mobile phase comprising of a mixture of ace¬tonitrile and phosphate buffer 20mM, pH 3.2 in the ratio 60:40 v/v. The flow rate was 1.0mL/min and column temperature was set to 30°C. The detection was carried out at 304 nm for ETR. Results and discussions: The cocrystals were subjected to various solid state characterization and the results confirmed the formation of cocrystals. The C=O stretching vibration (1741cm-1) in tartaric acid was disappeared in the cocrystal and the peak broadening of primary amine indicates hydrogen bond formation. The difference in the melting point of cocrystals when compared to pure Etravirine (265 °C) indicates interaction between the drug and the coformer which proves that first ordered transformation i.e. melting endotherm has disappeared. The difference in 2θ values of pure drug and cocrystals indicates the interaction between the drug and the coformer. Dynamic solubility and dissolution studies were also conducted by shake flask method and USP apparatus one respectively and 3.6 fold increase in the dynamic solubility were observed and in-vitro dissolution study shows four fold increase in the solubility for the ETR: TAR (1:1) cocrystals. The ETR: TAR (1:1) cocrystals shows improved solubility and dissolution as compared to the pure drug which was clearly showed by solid state characterization and dissolution studies.

Keywords: dynamic solubility, Etraverine, in vitro dissolution, slurry method

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Authors: Thiago E. Goto, Carla C. Lopes, Helena B. Nader, Anielle C. A. Silva, Noelio O. Dantas, José R. Siqueira Jr., Luciano Caseli

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Quantum dots (QD) are semiconductor nanocrystals that can be employed in biological research as a tool for fluorescence imagings, having the potential to expand in vivo and in vitro analysis as cancerous cell biomarkers. Particularly, cadmium selenide (CdSe) magic-sized quantum dots (MSQDs) exhibit stable luminescence that is feasible for biological applications, especially for imaging of tumor cells. For these facts, it is interesting to know the mechanisms of action of how such QDs mark biological cells. For that, simplified models are a suitable strategy. Among these models, Langmuir films of lipids formed at the air-water interface seem to be adequate since they can mimic half a membrane. They are monomolecular films formed at liquid-gas interfaces that can spontaneously form when organic solutions of amphiphilic compounds are spread on the liquid-gas interface. After solvent evaporation, the monomolecular film is formed, and a variety of techniques, including tensiometric, spectroscopic and optic can be applied. When the monolayer is formed by membrane lipids at the air-water interface, a model for half a membrane can be inferred where the aqueous subphase serve as a model for external or internal compartment of the cell. These films can be transferred to solid supports forming the so-called Langmuir-Blodgett (LB) films, and an ampler variety of techniques can be additionally used to characterize the film, allowing for the formation of devices and sensors. With these ideas in mind, the objective of this work was to investigate the specific interactions of CdSe MSQDs with tumorigenic and non-tumorigenic cells using Langmuir monolayers and LB films of lipids and specific cell extracts as membrane models for diagnosis of cancerous cells. Surface pressure-area isotherms and polarization modulation reflection-absorption spectroscopy (PM-IRRAS) showed an intrinsic interaction between the quantum dots, inserted in the aqueous subphase, and Langmuir monolayers, constructed either of selected lipids or of non-tumorigenic and tumorigenic cells extracts. The quantum dots expanded the monolayers and changed the PM-IRRAS spectra for the lipid monolayers. The mixed films were then compressed to high surface pressures and transferred from the floating monolayer to solid supports by using the LB technique. Images of the films were then obtained with atomic force microscopy (AFM) and confocal microscopy, which provided information about the morphology of the films. Similarities and differences between films with different composition representing cell membranes, with or without CdSe MSQDs, was analyzed. The results indicated that the interaction of quantum dots with the bioinspired films is modulated by the lipid composition. The properties of the normal cell monolayer were not significantly altered, whereas for the tumorigenic cell monolayer models, the films presented significant alteration. The images therefore exhibited a stronger effect of CdSe MSQDs on the models representing cancerous cells. As important implication of these findings, one may envisage for new bioinspired surfaces based on molecular recognition for biomedical applications.

Keywords: biomembrane, langmuir monolayers, quantum dots, surfaces

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Authors: José Manuel Palma, Paula Pereira, Margarida Tomás

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Foreseen the future: Human factors integration in European Horizon Projects The development of new technology as artificial intelligence, smart sensing, robotics, cobotics or intelligent machinery must integrate human factors to address the need to optimize systems and processes, thereby contributing to the creation of a safe and accident-free work environment. Human Factors Integration (HFI) consistently pose a challenge for organizations when applied to daily operations. AGILEHAND and FORTIS projects are grounded in the development of cutting-edge technology - industry 4.0 and 5.0. AGILEHAND aims to create advanced technologies for autonomously sort, handle, and package soft and deformable products, whereas FORTIS focuses on developing a comprehensive Human-Robot Interaction (HRI) solution. Both projects employ different approaches to explore HFI. AGILEHAND is mainly empirical, involving a comparison between the current and future work conditions reality, coupled with an understanding of best practices and the enhancement of safety aspects, primarily through management. FORTIS applies HFI throughout the project, developing a human-centric approach that includes understanding human behavior, perceiving activities, and facilitating contextual human-robot information exchange. it intervention is holistic, merging technology with the physical and social contexts, based on a total safety culture model. In AGILEHAND we will identify safety emergent risks, challenges, their causes and how to overcome them by resorting to interviews, questionnaires, literature review and case studies. Findings and results will be presented in “Strategies for Workers’ Skills Development, Health and Safety, Communication and Engagement” Handbook. The FORTIS project will implement continuous monitoring and guidance of activities, with a critical focus on early detection and elimination (or mitigation) of risks associated with the new technology, as well as guidance to adhere correctly with European Union safety and privacy regulations, ensuring HFI, thereby contributing to an optimized safe work environment. To achieve this, we will embed safety by design, and apply questionnaires, perform site visits, provide risk assessments, and closely track progress while suggesting and recommending best practices. The outcomes of these measures will be compiled in the project deliverable titled “Human Safety and Privacy Measures”. These projects received funding from European Union’s Horizon 2020/Horizon Europe research and innovation program under grant agreement No101092043 (AGILEHAND) and No 101135707 (FORTIS).

Keywords: human factors integration, automation, digitalization, human robot interaction, industry 4.0 and 5.0

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Authors: Varun Kumar, Chandra Shakher

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Micro-optical components such as microlenses and microlens array have numerous engineering and industrial applications for collimation of laser diodes, imaging devices for sensor system (CCD/CMOS, document copier machines etc.), for making beam homogeneous for high power lasers, a critical component in Shack-Hartmann sensor, fiber optic coupling and optical switching in communication technology. Also micro-optical components have become an alternative for applications where miniaturization, reduction of alignment and packaging cost are necessary. The compliance with high-quality standards in the manufacturing of micro-optical components is a precondition to be compatible on worldwide markets. Therefore, high demands are put on quality assurance. For quality assurance of these lenses, an economical measurement technique is needed. For cost and time reason, technique should be fast, simple (for production reason), and robust with high resolution. The technique should provide non contact, non-invasive and full field information about the shape of micro- optical component under test. The interferometric techniques are noncontact type and non invasive and provide full field information about the shape of the optical components. The conventional interferometric technique such as holographic interferometry or Mach-Zehnder interferometry is available for characterization of micro-lenses. However, these techniques need more experimental efforts and are also time consuming. Digital holography (DH) overcomes the above described problems. Digital holographic microscopy (DHM) allows one to extract both the amplitude and phase information of a wavefront transmitted through the transparent object (microlens or microlens array) from a single recorded digital hologram by using numerical methods. Also one can reconstruct the complex object wavefront at different depths due to numerical reconstruction. Digital holography provides axial resolution in nanometer range while lateral resolution is limited by diffraction and the size of the sensor. In this paper, Mach-Zehnder based digital holographic interferometric microscope (DHIM) system is used for the testing of transparent microlenses. The advantage of using the DHIM is that the distortions due to aberrations in the optical system are avoided by the interferometric comparison of reconstructed phase with and without the object (microlens array). In the experiment, first a digital hologram is recorded in the absence of sample (microlens array) as a reference hologram. Second hologram is recorded in the presence of microlens array. The presence of transparent microlens array will induce a phase change in the transmitted laser light. Complex amplitude of object wavefront in presence and absence of microlens array is reconstructed by using Fresnel reconstruction method. From the reconstructed complex amplitude, one can evaluate the phase of object wave in presence and absence of microlens array. Phase difference between the two states of object wave will provide the information about the optical path length change due to the shape of the microlens. By the knowledge of the value of the refractive index of microlens array material and air, the surface profile of microlens array is evaluated. The Sag of microlens and radius of curvature of microlens are evaluated and reported. The sag of microlens agrees well within the experimental limit as provided in the specification by the manufacturer.

Keywords: micro-optics, microlens array, phase map, digital holographic interferometric microscopy

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Authors: Zélia Maria Da Costa Ludwig, Maria José Valenzuela Bell, Geraldo Henriques Da Silva, Thales Alves Faraco, Victor Rocha Da Silva, Daniel Rotmeister Teixeira, Vírgilio De Carvalho Dos Anjos, Valdemir Ludwig

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Advances in telecommunications grow with the development of optical amplifiers based on rare earth ions. The focus has been concentrated in silicate glasses although their amplified spontaneous emission is limited to a few tens of nanometers (~ 40nm). Recently, phosphate glasses have received great attention due to their potential application in optical data transmission, detection, sensors and laser detector, waveguide and optical fibers, besides its excellent physical properties such as high thermal expansion coefficients and low melting temperature. Compared with the silica glasses, phosphate glasses provide different optical properties such as, large transmission window of infrared, and good density. Research on the improvement of physical and chemical durability of phosphate glass by addition of heavy metals oxides in P2O5 has been performed. The addition of Na2O further improves the solubility of rare earths, while increasing the Al2O3 links in the P2O5 tetrahedral results in increased durability and aqueous transition temperature and a decrease of the coefficient of thermal expansion. This work describes the structural and spectroscopic characterization of a phosphate glass matrix doped with different Er (Erbium) concentrations. The phosphate glasses containing Er3+ ions have been prepared by melt technique. A study of the optical absorption, luminescence and lifetime was conducted in order to characterize the infrared emission of Er3+ ions at 1540 nm, due to the radiative transition 4I13/2 → 4I15/2. Our results indicate that the present glass is a quite good matrix for Er3+ ions, and the quantum efficiency of the 1540 nm emission was high. A quenching mechanism for the mentioned luminescence was not observed up to 2,0 mol% of Er concentration. The Judd-Ofelt parameters, radiative lifetime and quantum efficiency have been determined in order to evaluate the potential of Er3+ ions in new phosphate glass. The parameters follow the trend as Ω2 > Ω4 > Ω6. It is well known that the parameter Ω2 is an indication of the dominant covalent nature and/or structural changes in the vicinity of the ion (short range effects), while Ω4 and Ω6 intensity parameters are long range parameters that can be related to the bulk properties such as viscosity and rigidity of the glass. From the PL measurements, no red or green upconversion was measured when pumping the samples with laser excitation at 980 nm. As future prospects: Synthesize this glass system with silver in order to determine the influence of silver nanoparticles on the Er3+ ions.

Keywords: phosphate glass, erbium, luminescence, glass system

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Authors: Paula I. Buonfiglio, Carlos David Bruque, Lucia Salatino, Vanesa Lotersztein, Sebastián Menazzi, Paola Plazas, Ana Belén Elgoyhen, Viviana Dalamón

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Hearing loss (HL) is the most prevalent sensorineural disorder affecting about 10% of the global population, with more than half due to genetic causes. About 1 in 500-1000 newborns present congenital HL. Most of the patients are non-syndromic with an autosomal recessive mode of inheritance. To date, more than 100 genes are related to HL. Therefore, the Whole-exome sequencing (WES) technique has become a cost-effective alternative approach for molecular diagnosis. Nevertheless, new challenges arise from the detection of novel variants, in particular missense changes, which can lead to a spectrum of genotype-to-phenotype correlations, which is not always straightforward. In this work, we aimed to identify the genetic causes of HL in isolated and familial cases by designing a multistep approach to analyze target genes related to hearing impairment. Moreover, we performed in silico and in vivo analyses in order to further study the effect of some of the novel variants identified in the hair cell function using the zebrafish model. A total of 650 patients were studied by Sanger Sequencing and Gap-PCR in GJB2 and GJB6 genes, respectively, diagnosing 15.5% of sporadic cases and 36% of familial ones. Overall, 50 different sequence variants were detected. Fifty of the undiagnosed patients with moderate HL were tested for deletions in STRC gene by Multiplex ligation-dependent probe amplification technique (MLPA), leading to 6% of diagnosis. After this initial screening, 50 families were selected to be analyzed by WES, achieving diagnosis in 44% of them. Half of the identified variants were novel. A missense variant in MYO6 gene detected in a family with postlingual HL was selected to be further analyzed. A protein modeling with AlphaFold2 software was performed, proving its pathogenic effect. In order to functionally validate this novel variant, a knockdown phenotype rescue assay in zebrafish was carried out. Injection of wild-type MYO6 mRNA in embryos rescued the phenotype, whereas using the mutant MYO6 mRNA (carrying c.2782C>A variant) had no effect. These results strongly suggest the deleterious effect of this variant on the mobility of stereocilia in zebrafish neuromasts, and hence on the auditory system. In the present work, we demonstrated that our algorithm is suitable for the sequential multigenic approach to HL in our cohort. These results highlight the importance of a combined strategy in order to identify candidate variants as well as the in silico and in vivo studies to analyze and prove their pathogenicity and accomplish a better understanding of the mechanisms underlying the physiopathology of the hearing impairment.

Keywords: diagnosis, genetics, hearing loss, in silico analysis, in vivo analysis, WES, zebrafish

Procedia PDF Downloads 71