Search results for: stem cell fate decision

Authors: Julio Jesus Salazar, Julio Jesus De Lama

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the fundamental objective of hydrological studies applied to the engineering field is to determine the statistically consistent volumes or water flows that, in each case, allow us to size or design a series of elements or structures to effectively manage and develop a river basin. To determine these values, there are several ways of working within the framework of traditional hydrology: (1) Study each of the factors that influence the hydrological cycle, (2) Study the historical behavior of the hydrology of the area, (3) Study the historical behavior of hydrologically similar zones, and (4) Other studies (rain simulators or experimental basins). Of course, this range of studies in a certain basin is very varied and complex and presents the difficulty of collecting the data in real time. In this complex space, the study of variables can only be overcome by collecting and transmitting data to decision centers through the Internet of things and artificial intelligence. Thus, this research work implemented the learning project of the sub-basin of the Shullcas river in the Andean basin of the Mantaro river in Peru. The sensor firmware to collect and communicate hydrological parameter data was programmed and tested in similar basins of the European Union. The Machine Learning applications was programmed to choose the algorithms that direct the best solution to the determination of the rainfall-runoff relationship captured in the different polygons of the sub-basin. Tests were carried out in the mountains of Europe, and in the sub-basins of the Shullcas river (Huancayo) and the Yauli river (Jauja) with heights close to 5000 m.a.s.l., giving the following conclusions: to guarantee a correct communication, the distance between devices should not pass the 15 km. It is advisable to minimize the energy consumption of the devices and avoid collisions between packages, the distances oscillate between 5 and 10 km, in this way the transmission power can be reduced and a higher bitrate can be used. In case the communication elements of the devices of the network (internet of things) installed in the basin do not have good visibility between them, the distance should be reduced to the range of 1-3 km. The energy efficiency of the Atmel microcontrollers present in Arduino is not adequate to meet the requirements of system autonomy. To increase the autonomy of the system, it is recommended to use low consumption systems, such as the Ashton Raggatt McDougall or ARM Cortex L (Ultra Low Power) microcontrollers or even the Cortex M; and high-performance direct current (DC) to direct current (DC) converters. The Machine Learning System has initiated the learning of the Shullcas system to generate the best hydrology of the sub-basin. This will improve as machine learning and the data entered in the big data coincide every second. This will provide services to each of the applications of the complex system to return the best data of determined flows.

Keywords: hydrology, internet of things, machine learning, river basin

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Authors: Mihaela Beregoi, Horia Iovu, Cristina Busuioc, Alexandru Evanghelidis, Elena Matei, Monica Enculescu, Ionut Enculescu

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Nanomaterials field is very attractive for all researchers who are attempting to develop new devices with the same or improved properties than the micro-sized ones, while reducing the reagents and power consumptions. In this way, a wide range of nanomaterials were fabricated and integrated in applications for electronics, optoelectronics, solar cells, tissue reconstruction and drug delivery. Obviously, the most appealing ones are those dedicated to the medical domain. Different types of nano-sized materials, such as particles, fibers, films etc., can be synthesized by using physical, chemical or electrochemical methods. One of these techniques is electrospinning, which enable the production of fibers with nanometric dimensions by pumping a polymeric solution in a high electric field; due to the electrostatic charging and solvent evaporation, the precursor mixture is converted into nonwoven meshes with different fiber densities and mechanical properties. Moreover, polyaniline is a conducting polymer with interesting optical properties, suitable for displays and electrochromic windows. Otherwise, polyaniline is an electroactive polymer that can contract/expand by applying electric stimuli, due to the oxidation/reduction reactions which take place in the polymer chains. These two main properties can be exploited in order to synthesize smart materials that change their dimensions, exhibiting in the same time good electrochromic properties. In the context aforesaid, a poly(methyl metacrylate) solution was spun to get webs composed of fibers with diameter values between 500 nm and 1 µm. Further, the polymer meshes were covered with a gold layer in order to make them conductive and also appropriate as working electrode in an electrochemical cell. The gold shell was deposited by DC sputtering. Such metalized fibers can be transformed into smart materials by covering them with a thin layer of conductive polymer. Thus, the webs were coated with a polyaniline film by the electrochemical route, starting from and aqueous solution of aniline and sulfuric acid, where sulfuric acid acts as oxidant agent. For the polymerization of aniline, a saturated calomel electrode was employed as reference, a platinum plate as counter electrode and the gold covered webs as working electrode. Chronoamperometry was selected as deposition method for polyaniline, by modifying the deposition time. Metalized meshes with different fiber densities were used, the transmission ranging between 70 and 80 %. The morphological investigation showed that polyaniline layer has a granular structure for all deposition experiments. As well, some preliminary optical tests were done by using sulfuric acid as electrolyte, which revealed the modification of polyaniline colour from green to dark blue when applying a voltage. In conclusion, new multilayered materials were obtained by a simple approach: the merge of the electrospinning method benefits with polyaniline chemistry. This synthesis method allows the fabrication of structures with reproducible characteristics, suitable for display or tissue substituents.

Keywords: electrospinning, fibers, smart materials, polyaniline

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

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

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

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Authors: Olugbenga S. Alebiosu, Olusola H. Adekanmbi, Oluwatoyin T. Ogundipe

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Pollen and spores have been identified as major airborne bio-particles inducing respiratory disorders such as asthma, allergic rhinitis and atopic dermatitis among hypersensitive individuals. An aeropalynological study was conducted within a one year sampling period with a view to investigating the monthly depositional rate of atmospheric pollen and spores; influence of the immediate vegetation on airborne pollen distribution; allergenic potentials of dominant atmospheric pollen types at selected study locations in Bauchi and Taraba states, Northwestern Nigeria. A tauber-like pollen trap was employed in aerosampling with the sampler positioned at a height of 5 feet above the ground, followed by a monthly collection of the recipient solution for the sampling period. The collected samples were subjected to acetolysis treatment, examined microscopically with the identification of pollen grains and spores using reference materials and published photomicrographs. Plants within the surrounding vegetation were enumerated. Crude protein contents extracted from pollen types found to be commonly dominant at both study locations; Senna siamea, Terminalia cattapa, Panicum maximum and Zea mays were used to sensitize Musmusculus. Histopathological studies of bronchi and lung sections from certain dead M.musculus in the test groups was conducted. Blood samples were collected from the pre-orbital vein of M.musculus and processed for serological and haematological (differential and total white blood cell counts) studies. ELISA was used in determining the levels of serological parameters: IgE and cytokines (TNF-, IL-5, and IL-13). Statistical significance was observed in the correlation between the levels of serological and haematological parameters elicited by each test group, differences between the levels of serological and haematological parameters elicited by each test group and those of the control, as well as at varying sensitization periods. The results from this study revealed dominant airborne pollen types across the study locations; Syzygiumguineense, Tridaxprocumbens, Elaeisguineensis, Mimosa sp., Borreria sp., Terminalia sp., Senna sp. and Poaceae. Nephrolepis sp., Pteris sp. and a trilete fern also produced spores. This study also revealed that some of the airborne pollen types were produced by local plants at the study locations. Bronchi sections of M.musculus after first and second sensitizations, as well as lung section after first sensitization with Senna siamea, showed areas of necrosis. Statistical significance was recorded in the correlation between the levels of some serological and haematological parameters produced by each test group and those of the control, as well as at certain sensitization periods. The study revealed some candidate pollen allergens at the study locations allergy sufferers and also established a complexity of interaction between immune cells, IgE and cytokines at varied periods of mice sensitization and forming a paradigm of human immune response to different pollen allergens. However, it is expedient that further studies should be conducted on these candidate pollen allergens for their allergenicity potential in humans within their immediate environment.

Keywords: airborne, hypersensitive, mus musculus, pollen allergens, respiratory, tauber-like

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Authors: Anda-veronica Gherman, Dimitrios Varthalitis

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Neurosurgery, like many surgical specialties, undoubtedly exhibits a significant gender gap, particularly in leadership positions. While increasing women representation in neurosurgery is important, it is crucial to increase their presence in leadership positions. Across the globe and Europe there are concerning trends of only 4% of all neurosurgical departments being chaired by women. This study aims to explore the situation regarding gender disparities in leadership in the United Kingdom and to identify possible contributing factors as well as discussing future strategies to bridge this gap. Methods: A literature review was conducted utilising PubMed as main database with search keywords including ‘female neurosurgeon’, ‘women neurosurgeon’, ‘gender disparity’, ‘leadership’ and ‘UK’. Additionally, a manual search of all neurosurgical departments in the UK was performed to identify the current female department leads and training director leads. Results: The literature search identified a paucity of literature addressing specifically leadership in female neurosurgeons within the UK, with very few published papers specifically on this topic. Despite more than half of medical students in the UK being female, only a small proportion pursue a surgical career, with neurosurgery being one of the least represented specialties. Only 27% of trainee neurosurgeons are female, and numbers are even lower at a consultant level, where women represent just 8%.Findings from published studies indicated that only 6.6% of leadership positions in neurosurgery are occupied by women in the UK. Furthermore, our manual searches across UK neurosurgical departments revealed that around 5% of department lead positions are currently held by women. While this figure is slightly higher than the European average of 4%, it remains lower compared to figures of 10% in other North-West European countries. The situation is slightly more positive looking at the training directors, with 15% being female. Discussion: The findings of this study highlight a significant gender disparity in leadership positions within neurosurgery in the UK, which may have important implications, perpetuating the lack of diversity on the decision-making process, limiting the career advancement opportunities of women and depriving the neurosurgical field from the voices, opinions and talents of women. With women representing half of the population, there is an undeniable need for more female leaders at the policy-making level. There are many barriers that can contribute to these numbers, including bias, stereotypes, lack of mentorship and work-like balance. A few solutions to overcome these barriers can be training programs addressing bias and impostor syndrome, leadership workshops tailored for female needs, better workplace policies, increased in formal mentorship and increasing the visibility of women in neurosurgery leadership positions through media, speaking opportunities, conferences, awards etc. And lastly, more research efforts should focus on the leadership and mentorship of women in neurosurgery, with an increased number of published papers discussing these issues.

Keywords: female neurosurgeons, female leadership, female mentorship, gender disparities

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Authors: Iman Farasat, Howard M. Salis

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Engineered genetic circuits reprogram cellular behavior to act as living computers with applications in detecting cancer, creating self-controlling artificial tissues, and dynamically regulating metabolic pathways. Phenemenological models are often used to simulate and design genetic circuit behavior towards a desired behavior. While such models assume that each circuit component’s function is modular and independent, even small changes in a circuit (e.g. a new promoter, a change in transcription factor expression level, or even a new media) can have significant effects on the circuit’s function. Here, we use statistical thermodynamics to account for the several factors that control transcriptional regulation in bacteria, and experimentally demonstrate the model’s accuracy across 825 measurements in several genetic contexts and hosts. We then employ our first principles model to design, experimentally construct, and characterize a family of signal amplifying genetic circuits (genetic OpAmps) that expand the dynamic range of cell sensors. To develop these models, we needed a new approach to measuring the in vivo binding free energies of transcription factors (TFs), a key ingredient of statistical thermodynamic models of gene regulation. We developed a new high-throughput assay to measure RNA polymerase and TF binding free energies, requiring the construction and characterization of only a few constructs and data analysis (Figure 1A). We experimentally verified the assay on 6 TetR-homolog repressors and a CRISPR/dCas9 guide RNA. We found that our binding free energy measurements quantitatively explains why changing TF expression levels alters circuit function. Altogether, by combining these measurements with our biophysical model of translation (the RBS Calculator) as well as other measurements (Figure 1B), our model can account for changes in TF binding sites, TF expression levels, circuit copy number, host genome size, and host growth rate (Figure 1C). Model predictions correctly accounted for how these 8 factors control a promoter’s transcription rate (Figure 1D). Using the model, we developed a design framework for engineering multi-promoter genetic circuits that greatly reduces the number of degrees of freedom (8 factors per promoter) to a single dimensionless unit. We propose the Ptashne (Pt) number to encapsulate the 8 co-dependent factors that control transcriptional regulation into a single number. Therefore, a single number controls a promoter’s output rather than these 8 co-dependent factors, and designing a genetic circuit with N promoters requires specification of only N Pt numbers. We demonstrate how to design genetic circuits in Pt number space by constructing and characterizing 15 2-repressor OpAmp circuits that act as signal amplifiers when within an optimal Pt region. We experimentally show that OpAmp circuits using different TFs and TF expression levels will only amplify the dynamic range of input signals when their corresponding Pt numbers are within the optimal region. Thus, the use of the Pt number greatly simplifies the genetic circuit design, particularly important as circuits employ more TFs to perform increasingly complex functions.

Keywords: transcription factor, synthetic biology, genetic circuit, biophysical model, binding energy measurement

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Authors: Mehrnaz Mostafavi

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The assessment and categorization of incidental lung nodules present a considerable challenge in healthcare, often necessitating resource-intensive multiple computed tomography (CT) scans for growth confirmation. This research addresses this issue by introducing a distinct computational approach leveraging radiomics and deep-learning methods. However, understanding local services is essential before implementing these advancements. With diverse tracking methods in place, there is a need for efficient and accurate identification approaches, especially in the context of managing lung nodules alongside pre-existing cancer scenarios. This study explores the integration of text-based algorithms in medical data curation, indicating their efficacy in conjunction with machine learning and deep-learning models for identifying lung nodules. Combining medical images with text data has demonstrated superior data retrieval compared to using each modality independently. While deep learning and text analysis show potential in detecting previously missed nodules, challenges persist, such as increased false positives. The presented research introduces a Structured-Query-Language (SQL) algorithm designed for identifying pulmonary nodules in a tertiary cancer center, externally validated at another hospital. Leveraging natural language processing (NLP) and machine learning, the algorithm categorizes lung nodule reports based on sentence features, aiming to facilitate research and assess clinical pathways. The hypothesis posits that the algorithm can accurately identify lung nodule CT scans and predict concerning nodule features using machine-learning classifiers. Through a retrospective observational study spanning a decade, CT scan reports were collected, and an algorithm was developed to extract and classify data. Results underscore the complexity of lung nodule cohorts in cancer centers, emphasizing the importance of careful evaluation before assuming a metastatic origin. The SQL and NLP algorithms demonstrated high accuracy in identifying lung nodule sentences, indicating potential for local service evaluation and research dataset creation. Machine-learning models exhibited strong accuracy in predicting concerning changes in lung nodule scan reports. While limitations include variability in disease group attribution, the potential for correlation rather than causality in clinical findings, and the need for further external validation, the algorithm's accuracy and potential to support clinical decision-making and healthcare automation represent a significant stride in lung nodule management and research.

Keywords: lung cancer diagnosis, structured-query-language (SQL), natural language processing (NLP), machine learning, CT scans

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Authors: Mehdi Boukri, Mohammed Naboussi Farsi, Mounir Naili, Omar Amellal, Mohamed Belazougui, Ahmed Mebarki, Nabila Guessoum, Brahim Mezazigh, Mounir Ait-Belkacem, Nacim Yousfi, Mohamed Bouaoud, Ikram Boukal, Aboubakr Fettar, Asma Souki

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The seismic risk to which the urban centres are more and more exposed became a world concern. A co-operation on an international scale is necessary for an exchange of information and experiments for the prevention and the installation of action plans in the countries prone to this phenomenon. For that, the 1990s was designated as 'International Decade for Natural Disaster Reduction (IDNDR)' by the United Nations, whose interest was to promote the capacity to resist the various natural, industrial and environmental disasters. Within this framework, it was launched in 1996, the RADIUS project (Risk Assessment Tools for Diagnosis of Urban Areas Against Seismic Disaster), whose the main objective is to mitigate seismic risk in developing countries, through the development of a simple and fast methodological and operational approach, allowing to evaluate the vulnerability as well as the socio-economic losses, by probable earthquake scenarios in the exposed urban areas. In this paper, we will present the adaptation and application of this methodology to the Algerian context for the seismic risk evaluation in urban areas potentially exposed to earthquakes. This application consists to perform an earthquake scenario in the urban centre of Constantine city, located at the North-East of Algeria, which will allow the building seismic damage estimation of this city. For that, an inventory of 30706 building units was carried out by the National Earthquake Engineering Research Centre (CGS). These buildings were digitized in a data base which comprises their technical information by using a Geographical Information system (GIS), and then they were classified according to the RADIUS methodology. The study area was subdivided into 228 meshes of 500m on side and Ten (10) sectors of which each one contains a group of meshes. The results of this earthquake scenario highlights that the ratio of likely damage is about 23%. This severe damage results from the high concentration of old buildings and unfavourable soil conditions. This simulation of the probable seismic damage of the building and the GIS damage maps generated provide a predictive evaluation of the damage which can occur by a potential earthquake near to Constantine city. These theoretical forecasts are important for decision makers in order to take the adequate preventive measures and to develop suitable strategies, prevention and emergency management plans to reduce these losses. They can also help to take the adequate emergency measures in the most impacted areas in the early hours and days after an earthquake occurrence.

Keywords: seismic risk, mitigation, RADIUS, urban areas, Algeria, earthquake scenario, Constantine

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Authors: László L. Lippai

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In addition to the fact that mental health bears great significance to a particular individual, it can also be regarded as an organizational, community and societal resource. Within the Szeged Health Promotion Research Group, we conducted mental health surveys on two levels: The inhabitants of a medium-sized Hungarian town and students of a Hungarian university with a relatively big headcount were requested to participate in surveys whose goals were to define local government priorities and organization-level health promotion programmes, respectively. To facilitate professional decision-making, we defined three, pragmatically relevant, groups of the target population: the mentally healthy, the vulnerable and the endangered. In order to determine which group a person actually belongs to, we designed a simple and quick measurement tool, which could even be utilised as a smoothing method, the Mental State Questionnaire validity of the above three categories was verified by analysis of variance against psychological quality of life variables. We demonstrate the pragmatic significance of our method via the analyses of the scores of our two mental health surveys. On town level, during our representative survey in Hódmezővásárhely (N=1839), we found that 38.7% of the participants was mentally healthy, 35.3% was vulnerable, while 16.3% was considered as endangered. We were able to identify groups that were in a dramatic state in terms of mental health. For example, such a group consisted of men aged 45 to 64 with only primary education qualification and the ratios of the mentally healthy, vulnerable and endangered were 4.5, 45.5 and 50%, respectively. It was also astonishing to see to what a little extent qualification prevailed as a protective factor in the case of women. Based on our data, the female group aged 18 to 44 with primary education—of whom 20.3% was mentally healthy, 42.4% vulnerable and 37.3% was endangered—as well as the female group aged 45 to 64 with university or college degree—of whom 25% was mentally healthy, 51.3 vulnerable and 23.8% endangered—are to be handled as priority intervention target groups in a similarly difficult position. On organizational level, our survey involving the students of the University of Szeged, N=1565, provided data to prepare a strategy of mental health promotion for a university with a headcount exceeding 20,000. When developing an organizational strategy, it was important to gather information to estimate the proportions of target groups in which mental health promotion methods; for example, life management skills development, detection, psychological consultancy, psychotherapy, would be applied. Our scores show that 46.8% of the student participants were mentally healthy, 42.1% were vulnerable and 11.1% were endangered. These data convey relevant information as to the allocation of organizational resources within a university with a considerable headcount. In conclusion, The Mental State Questionnaire, as a valid smoothing method, is adequate to describe a community in a plain and informative way in the terms of mental health. The application of the method can promote the preparation, design and implementation of mental health promotion interventions. 

Keywords: health promotion, mental health promotion, mental state questionnaire, psychological well-being

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Authors: O. Squillace, R. L. Thompson

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Migration of small molecules to, and across the surface of polymer matrices is a little-studied problem with important industrial applications. Tackifiers in adhesives, flavors in foods and binding agents in paints all present situations where the function of a product depends on the ability of small molecules to migrate through a polymer matrix to achieve the desired properties such as softness, dispersion of fillers, and to deliver an effect that is felt (or tasted) on a surface. It’s been shown that the chemical and molecular structure, surface free energies, phase behavior, close environment and compatibility of the system, influence the migrants’ motion. When differences in behavior, such as occurrence of segregation to the surface or not, are observed it is then of crucial importance to identify and get a better understanding of the driving forces involved in the process of molecular migration. In this aim, experience is meant to be allied with theory in order to deliver a validated theoretical and computational toolkit to describe and predict these phenomena. The systems that have been chosen for this study aim to address the effect of polarity mismatch between the migrants and the polymer matrix and that of a second migrant over the first one. As a non-polar resin polymer, polyvinyl acetate is used as the material to which more or less polar migrants (sorbitol, carvone, octanoic acid (OA), triacetin) are to be added. Through contact angle measurement a surface excess is seen for sorbitol (polar) mixed with PVAc as the surface energy is lowered compare to the one of pure PVAc. This effect is increased upon the addition of carvon or triacetin (non-polars). Surface micro-structures are also evidenced by atomic force microscopy (AFM). Ion beam analysis (Nuclear Reaction Analysis), supplemented by neutron reflectometry can accurately characterize the self-organization of surfactants, oligomers, aromatic molecules in polymer films in order to relate the macroscopic behavior to the length scales that are amenable to simulation. The nuclear reaction analysis (NRA) data for deuterated OA 20% shows the evidence of a surface excess which is enhanced after annealing. The addition of 10% triacetin, as a second migrant, results in the formation of an underlying layer enriched in triacetin below the surface excess of OA. The results show that molecules in polarity mismatch with the matrix tend to segregate to the surface, and this is favored by the addition of a second migrant of the same polarity than the matrix. As studies have been restricted to materials that are model supported films under static conditions in a first step, it is also wished to address the more challenging conditions of materials under controlled stress or strain. To achieve this, a simple rig and PDMS cell have been designed to stretch the material to a defined strain and to probe these mechanical effects by ion beam analysis and atomic force microscopy. This will make a significant step towards exploring the influence of extensional strain on surface segregation, flavor release in cross-linked rubbers.

Keywords: polymers, surface segregation, thin films, molecular migration

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Authors: Vrushali Guhe, Shailza Singh

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Cutaneous leishmaniasis is neglected tropical disease present worldwide caused by the protozoan parasite Leishmania major, the therapeutic armamentarium for leishmaniasis are showing several limitations as drugs are showing toxic effects with increasing resistance by a parasite. Thus identification of novel therapeutic targets is of paramount importance. Previous studies have shown that autophagy, a cellular process, can either facilitate infection or aid in the elimination of the parasite, depending on the specific parasite species and host background in leishmaniasis. In the present study, our objective was to target the essential autophagy protein ATG8, which plays a crucial role in the survival, infection dynamics, and differentiation of the Leishmania parasite. ATG8 in Leishmania major and its homologue, LC3, in Homo sapiens, act as autophagic markers. Present study manifested the crucial role of ATG8 protein as a potential target for combating Leishmania major infection. Through bioinformatics analysis, we identified non-conserved motifs within the ATG8 protein of Leishmania major, which are not present in LC3 of Homo sapiens. Against these two non-conserved motifs, we generated a peptide library of 60 peptides on the basis of physicochemical properties. These peptides underwent a filtering process based on various parameters, including feasibility of synthesis and purification, compatibility with Selective Reaction Monitoring (SRM)/Multiple reaction monitoring (MRM), hydrophobicity, hydropathy index, average molecular weight (Mw average), monoisotopic molecular weight (Mw monoisotopic), theoretical isoelectric point (pI), and half-life. Further filtering criterion shortlisted three peptides by using molecular docking and molecular dynamics simulations. The direct interaction between ATG8 and the shortlisted peptides was confirmed through Surface Plasmon Resonance (SPR) experiments. Notably, these peptides exhibited the remarkable ability to penetrate the parasite membrane and exert profound effects on Leishmania major. The treatment with these peptides significantly impacted parasite survival, leading to alterations in the cell cycle and morphology. Furthermore, the peptides were found to modulate autophagosome formation, particularly under starved conditions, suggesting their involvement in disrupting the regulation of autophagy within Leishmania major. In vitro, studies demonstrated that the selected peptides effectively reduced the parasite load within infected host cells. Encouragingly, these findings were corroborated by in vivo experiments, which showed a reduction in parasite burden upon peptide administration. Additionally, the peptides were observed to affect the levels of LC3II within host cells. In conclusion, our findings highlight the efficacy of these novel peptides in targeting Leishmania major’s ATG8 and disrupting parasite survival. These results provide valuable insights into the development of innovative therapeutic strategies against leishmaniasis via targeting autophagy protein ATG8 of Leishmania major.

Keywords: ATG8, leishmaniasis, surface plasmon resonance, MD simulation, molecular docking, peptide designing, therapeutics

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Authors: John Zanetich

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Due to their positive associations with student learning and retention, certain undergraduate opportunities are designated ‘high-impact.’ High-Impact Practices (HIPs) such as, learning communities, community based projects, research, internships, study abroad and culminating senior experience, share several traits bin common: they demand considerable time and effort, learning occurs outside of the classroom, and they require meaningful interactions between faculty and students, they encourage collaboration with diverse others, and they provide frequent and substantive feedback. As a result of experiential learning in these practices, participation in these practices can be life changing. High impact learning helps individuals locate tacit knowledge, and build mental models that support the accumulation of knowledge. On-going learning from experience and knowledge conversion provides the individual with a way to implicitly organize knowledge and share knowledge over a lifetime. Knowledge conversion is a knowledge management component which focuses on the explication of the tacit knowledge that exists in the minds of students and that knowledge which is embedded in the process and relationships of the classroom educational experience. Knowledge conversion is required when working with tacit knowledge and the demand for a learner to align deeply held beliefs with the cognitive dissonance created by new information. Knowledge conversion and tacit knowledge result from the fact that an individual's way of knowing, that is, their core belief structure, is considered generalized and tacit instead of explicit and specific. As a phenomenon, tacit knowledge is not readily available to the learner for explicit description unless evoked by an external source. The development of knowledge–related capabilities such as Aggressive Development of Tacit Knowledge (ADTK) can be used in experiential educational programs to enhance knowledge, foster behavioral change, improve decision making, and overall performance. ADTK allows the student in HIPs to use their existing knowledge in a way that allows them to evaluate and make any necessary modifications to their core construct of reality in order to amalgamate new information. Based on the Lewin/Schein Change Theory, the learner will reach for tacit knowledge as a stabilizing mechanism when they are challenged by new information that puts them slightly off balance. As in word association drills, the important concept is the first thought. The reactionary outpouring to an experience is the programmed or tacit memory and knowledge of their core belief structure. ADTK is a way to help teachers design their own methods and activities to unfreeze, create new learning, and then refreeze the core constructs upon which future learning in a subject area is built. This paper will explore the use of ADTK as a technique for knowledge conversion in the classroom in general and in HIP programs specifically. It will focus on knowledge conversion in curriculum development and propose the use of one-time educational experiences, multi-session experiences and sequential program experiences focusing on tacit knowledge in educational programs.

Keywords: tacit knowledge, knowledge management, college programs, experiential learning

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Authors: Julia Ive, Lucia Specia

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Understanding and detecting toxicity is an important problem to support safer human interactions online. Our work focuses on the important problem of contextual toxicity detection, where automated classifiers are tasked with determining whether a short textual segment (usually a sentence) is toxic within its conversational context. We use “toxicity” as an umbrella term to denote a number of variants commonly named in the literature, including hate, abuse, offence, among others. Detecting toxicity in context is a non-trivial problem and has been addressed by very few previous studies. These previous studies have analysed the influence of conversational context in human perception of toxicity in controlled experiments and concluded that humans rarely change their judgements in the presence of context. They have also evaluated contextual detection models based on state-of-the-art Deep Learning and Natural Language Processing (NLP) techniques. Counterintuitively, they reached the general conclusion that computational models tend to suffer performance degradation in the presence of context. We challenge these empirical observations by devising better contextual predictive models that also rely on NLP data augmentation techniques to create larger and better data. In our study, we start by further analysing the human perception of toxicity in conversational data (i.e., tweets), in the absence versus presence of context, in this case, previous tweets in the same conversational thread. We observed that the conclusions of previous work on human perception are mainly due to data issues: The contextual data available does not provide sufficient evidence that context is indeed important (even for humans). The data problem is common in current toxicity datasets: cases labelled as toxic are either obviously toxic (i.e., overt toxicity with swear, racist, etc. words), and thus context does is not needed for a decision, or are ambiguous, vague or unclear even in the presence of context; in addition, the data contains labeling inconsistencies. To address this problem, we propose to automatically generate contextual samples where toxicity is not obvious (i.e., covert cases) without context or where different contexts can lead to different toxicity judgements for the same tweet. We generate toxic and non-toxic utterances conditioned on the context or on target tweets using a range of techniques for controlled text generation(e.g., Generative Adversarial Networks and steering techniques). On the contextual detection models, we posit that their poor performance is due to limitations on both of the data they are trained on (same problems stated above) and the architectures they use, which are not able to leverage context in effective ways. To improve on that, we propose text classification architectures that take the hierarchy of conversational utterances into account. In experiments benchmarking ours against previous models on existing and automatically generated data, we show that both data and architectural choices are very important. Our model achieves substantial performance improvements as compared to the baselines that are non-contextual or contextual but agnostic of the conversation structure.

Keywords: contextual toxicity detection, data augmentation, hierarchical text classification models, natural language processing

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Authors: Bagireanu Astrid, Bros-Williamson Julio, Duncheva Mila, Currie John

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The Architecture, Engineering, and Construction (AEC) sector plays a critical role in the global transition toward sustainable and net-zero built environments. However, the industry faces unique challenges in planning for net-zero while struggling with low productivity, cost overruns and overall resistance to change. Traditional practices fall short due to their inability to meet the requirements for systemic change, especially as governments increasingly demand transformative approaches. Working in silos and rigid hierarchies and a short-term, client-centric approach prioritising immediate gains over long-term benefit stands in stark contrast to the fundamental requirements for the realisation of net-zero objectives. These practices have limited capacity to effectively integrate AEC stakeholders and promote the essential knowledge sharing required to address the multifaceted challenges of achieving net-zero. In the context of built environment, procurement may be described as the method by which a project proceeds from inception to completion. Collaborative procurement methods under the Integrated Practices (IP) umbrella have the potential to align more closely with net-zero objectives. This paper explores the synergies between collaborative procurement principles and the pursuit of net zero in the AEC sector, drawing upon the shared values of cross-disciplinary collaboration, Early Supply Chain involvement (ESI), use of standards and frameworks, digital information management, strategic performance measurement, integrated decision-making principles and contractual alliancing. To investigate the role of collaborative procurement in advancing net-zero objectives, a structured research methodology was employed. First, the study focuses on a systematic review on the application of collaborative procurement principles in the AEC sphere. Next, a comprehensive analysis is conducted to identify common clusters of these principles across multiple procurement methods. An evaluative comparison between traditional procurement methods and collaborative procurement for achieving net-zero objectives is presented. Then, the study identifies the intersection between collaborative procurement principles and the net-zero requirements. Lastly, an exploration of key insights for AEC stakeholders focusing on the implications and practical applications of these findings is made. Directions for future development of this research are recommended. Adopting collaborative procurement principles can serve as a strategic framework for guiding the AEC sector towards realising net-zero. Synergising these approaches overcomes fragmentation, fosters knowledge sharing, and establishes a net-zero-centered ecosystem. In the context of the ongoing efforts to amplify project efficiency within the built environment, a critical realisation of their central role becomes imperative for AEC stakeholders. When effectively leveraged, collaborative procurement emerges as a powerful tool to surmount existing challenges in attaining net-zero objectives.

Keywords: collaborative procurement, net-zero, knowledge sharing, architecture, built environment

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Authors: E. Mosiniewicz-Szablewska, P. Suchocki, P. C. Morais

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Despite the significant progress in cancer treatment, there is a need to search for new therapeutic methods in order to minimize side effects. Chemotherapy, the main current method of treating cancer, is non-selective and has a number of limitations. Toxicity to healthy cells is undoubtedly the biggest problem limiting the use of many anticancer drugs. The problem of how to kill cancer without harming a patient can be solved by using organic selenium (IV) compounds. Organic selenium (IV) compounds are a new class of materials showing a strong anticancer activity. They are first organic compounds containing selenium at the +4 oxidation level and therefore they eliminate the multidrug-resistance for all tumor cell lines tested so far. These materials are capable of selectively killing cancer cells without damaging the healthy ones. They are obtained by the incorporation of selenous acid (H2SeO3) into molecules of fatty acids of sunflower oil and therefore, they are inexpensive to manufacture. Attaching these compounds to magnetic carriers enables their precise delivery directly to the tumor area and the simultaneous application of the magnetic hyperthermia, thus creating a huge opportunity to effectively get rid of the tumor without any side effects. Polylactic-co-glicolic acid (PLGA) nanocapsules loaded with maghemite (-Fe2O3) nanoparticles and organic selenium (IV) compounds are successfully prepared by nanoprecipitation method. In vitro antitumor activity of the nanocapsules were evidenced using murine melanoma (B16-F10), oral squamos carcinoma (OSCC) and murine (4T1) and human (MCF-7) breast lines. Further exposure of these cells to an alternating magnetic field increased the antitumor effect of nanocapsules. Moreover, the nanocapsules presented antitumor effect while not affecting normal cells. Magnetic properties of the nanocapsules were investigated by means of dc magnetization, ac susceptibility and electron spin resonance (ESR) measurements. The nanocapsules presented a typical superparamagnetic behavior around room temperature manifested itself by the split between zero field-cooled/field-cooled (ZFC/FC) magnetization curves and the absence of hysteresis on the field-dependent magnetization curve above the blocking temperature. Moreover, the blocking temperature decreased with increasing applied magnetic field. The superparamagnetic character of the nanocapsules was also confirmed by the occurrence of a maximum in temperature dependences of both real ′(T) and imaginary ′′ (T) components of the ac magnetic susceptibility, which shifted towards higher temperatures with increasing frequency. Additionally, upon decreasing the temperature the ESR signal shifted to lower fields and gradually broadened following closely the predictions for the ESR of superparamagnetoc nanoparticles. The observed superparamagnetic properties of nanocapsules enable their simple manipulation by means of magnetic field gradient, after introduction into the blood stream, which is a necessary condition for their use as magnetic drug carriers. The observed anticancer and superparamgnetic properties show that the magnetic nanocapsules loaded with organic selenium (IV) compounds should be considered as an effective material system for magnetic drug delivery and magnetohyperthermia inductor in antitumor therapy.

Keywords: cancer treatment, magnetic drug delivery system, nanomaterials, nanotechnology

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Authors: Priyanka Jain, Ashish K. Sharma, Esha Shukla, K. J. Mukherjee

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We propose a paradigm shift in our approach to design improved platforms for recombinant protein production, by addressing system level issues rather than the individual steps associated with recombinant protein synthesis like transcription, translation, etc. We demonstrate that by controlling and modulating the cellular stress response (CSR), which is responsible for feedback control of protein synthesis, we can generate hyper-producing strains. We did transcriptomic profiling of post-induction cultures, expressing different types of protein, to analyze the nature of this cellular stress response. We found significant down-regulation of substrate utilization, translation, and energy metabolism genes due to generation CSR inside the host cell. However, transcription profiling has also shown that many genes are up-regulated post induction and their role in modulating the CSR is unclear. We hypothesized that these up-regulated genes trigger signaling pathways, generating the CSR and concomitantly reduce the recombinant protein yield. To test this hypothesis, we knocked out the up-regulated genes, which did not have any downstream regulatees, and analyzed their impact on cellular health and recombinant protein expression. Two model proteins i.e., GFP and L-Asparaginase were chosen for this analysis. We observed a significant improvement in expression levels, with some knock-outs showing more than 7-fold higher expression compared to control. The 10 best single knock-outs were chosen to make 45 combinations of all possible double knock-outs. A further increase in expression was observed in some of these double knock- outs with GFP levels being highest in a double knock-out ΔyhbC + ΔelaA. However, for L-Asparaginase which is a secretory protein, the best results were obtained using a combination of ΔelaA+ΔcysW knock-outs. We then tested all the knock outs for their ability to enhance the expression of a 'difficult-to-express' protein. The Rubella virus E1 protein was chosen and tagged with sfGFP at the C-terminal using a linker peptide for easy online monitoring of expression of this fusion protein. Interestingly, the highest increase in Rubella-sGFP levels was obtained in the same double knock-out ΔelaA + ΔcysW (5.6 fold increase in expression yield compared to the control) which gave the highest expression for L-Asparaginase. However, for sfGFP alone, the ΔyhbC+ΔmarR knock-out gave the highest level of expression. These results indicate that there is a fair degree of commonality in the nature of the CSR generated by the induction of different proteins. Transcriptomic profiling of the double knock out showed that many genes associated with the translational machinery and energy biosynthesis did not get down-regulated post induction, unlike the control where these genes were significantly down-regulated. This confirmed our hypothesis of these genes playing an important role in the generation of the CSR and allowed us to design a strategy for making better expression hosts by simply knocking out key genes. This strategy is radically superior to the previous approach of individually up-regulating critical genes since it blocks the mounting of the CSR thus preventing the down-regulation of a very large number of genes responsible for sustaining the flux through the recombinant protein production pathway.

Keywords: cellular stress response, GFP, knock-outs, up-regulated genes

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Authors: Xabier Barandiaran, Igone Guerra

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The economic and financial crisis that hit European countries in 2008 revealed the inability of governments to respond unilaterally to the so-called “wicked” problems that affect our societies. Closely linked to this, the increasing disaffection of citizens towards politics has resulted in growing distrust of the citizenry not only in the institutions in general but also in the political system, in particular. Precisely, these two factors provoked the action of the local government of Gipuzkoa (Basque Country) to move from old ways of “doing politics” to a new way of “thinking politics” based on a collaborative approach, in which innovative modes of public decision making are prominent. In this context, in 2015, the initiative Etorkizuna Eraikiz (Building the Future), a contemporary form of networked governance, was launched by the Provincial Government. The paper focuses on the Etorkizuna Eraikiz initiative, a sound commitment from a local government to build jointly with the citizens the future of the territory. This paper will present preliminary results obtained from three different experiences of co-creation developed within Etorkizuna Eraikiz in which the formulation of networked governance is a mandatory pre-requisite. These experiences show how the network building approach among the different agents of the territory as well as the co-creation of public policies is the cornerstone of this challenging mission. Through the analysis of the information and documentation gathered during the four years of Etorkizuna-Eraikiz, and, specifically by delving into the strategy promoted by the initiative, some emerging analytical conclusions resulting from the promotion of this collaborative culture will be presented. For example, some preliminary results have shown a significant positive relationship between shared leadership and the formulation of the public good. In the period 2016-2018, a total of 73 projects were launched and funding by the Provincial Government of Gipuzkoa within the Etorkizuna Eraikiz initiative, that indicates greater engagement of the citizenry in the process of policy-making and therefore improving, somehow, the quality of the public policies. These statements have been supported by the last survey about the perspectives of the citizens toward politics and policies. Some of the more prominent results show us that there is still a high level of distrust in Politics (78,9% of respondents) but a greater trust in institutions such the Political Government of Gipuzkoa (40,8% of respondents declared as “good” the performance of this provincial institution). Regarding the Etorkizuna Eraikiz Initiative, it is being more readily recognized by citizens over this period of time (25,4% of the respondents in June 2018 agreed to know about the initiative giving it a mark of 5,89 ) and thus build trust and a sense of ownership. Although, there is a clear requirement for further research on the linkages between collaborative governance and level of trust, the paper, based on these findings, will provide some managerial and theoretical implications for collaborative governance in the territory.

Keywords: network governance, collaborative governance, public sector innovation, citizen participation, trust

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Authors: Nutcha Taneepanichskul, Helen C. Hailes, Mark Miodownik

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Plastic waste has emerged as a critical global environmental challenge, primarily driven by the prevalent use of conventional plastics derived from petrochemical refining and manufacturing processes in modern packaging. While these plastics serve vital functions, their persistence in the environment post-disposal poses significant threats to ecosystems. Addressing this issue necessitates approaches, one of which involves the development of biodegradable plastics designed to degrade under controlled conditions, such as industrial composting facilities. It is imperative to note that compostable plastics are engineered for degradation within specific environments and are not suited for uncontrolled settings, including natural landscapes and aquatic ecosystems. The full benefits of compostable packaging are realized when subjected to industrial composting, preventing environmental contamination and waste stream pollution. Therefore, effective sorting technologies are essential to enhance composting rates for these materials and diminish the risk of contaminating recycling streams. In this study, it leverage hyperspectral imaging technology (HSI) coupled with advanced machine learning algorithms to accurately identify various types of plastics, encompassing conventional variants like Polyethylene terephthalate (PET), Polypropylene (PP), Low density polyethylene (LDPE), High density polyethylene (HDPE) and biodegradable alternatives such as Polybutylene adipate terephthalate (PBAT), Polylactic acid (PLA), and Polyhydroxyalkanoates (PHA). The dataset is partitioned into three subsets: a training dataset comprising uncontaminated conventional and biodegradable plastics, a validation dataset encompassing contaminated plastics of both types, and a testing dataset featuring real-world packaging items in both pristine and contaminated states. Five distinct machine learning algorithms, namely Partial Least Squares Discriminant Analysis (PLS-DA), Support Vector Machine (SVM), Convolutional Neural Network (CNN), Logistic Regression, and Decision Tree Algorithm, were developed and evaluated for their classification performance. Remarkably, the Logistic Regression and CNN model exhibited the most promising outcomes, achieving a perfect accuracy rate of 100% for the training and validation datasets. Notably, the testing dataset yielded an accuracy exceeding 80%. The successful implementation of this sorting technology within recycling and composting facilities holds the potential to significantly elevate recycling and composting rates. As a result, the envisioned circular economy for plastics can be established, thereby offering a viable solution to mitigate plastic pollution.

Keywords: biodegradable plastics, sorting technology, hyperspectral imaging technology, machine learning algorithms

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Authors: Krzysztof Gwozdzinski, Janusz Mazur

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Bory Tucholskie (Tucholskie Forest) is one of the largest pine forest complexes in Poland. It occupies approx. 3,000 square kilometers of Sandr in the Brda and Wda basin and the Tuchola Plain and the Charzykowskie Plain. Since 2010 it has transformed into The Bory Tucholskie Biosphere Reserve, according to the UNESCO decision. The area of the Bory Tucholskie National Park (BTNP), the park area, has been designated in 1996. There is little data on the presence of heavy metals in the Park's lakes. Concentration of heavy metals in the water of 19 lakes in the BTNP was examined. The lakes were divided into two groups: subglacial channel lakes of Struga Siedmiu Jezior (the Seven Lakes Stream) and other lakes. Heavy metals (transition metals) belong to d-block of elements. The part of these metals plays an important role in the function of living organisms as metalloproteins (enzymes, hemoproteins, vitamins, etc.). However, heavy metals are also typical; heavy metals are typical anthropogenic pollutants. Water samples were collected at the deepest points of lakes during spring and during summer stagnation. The analysis of metals was performed in an atomic absorption spectrophotometer Varian Spectra A300/400 in electric atomizer (GTA 96) in graphite cuvette. In the waters of the Seven Lakes Stream (Ostrowite, Zielone, Jelen, Belczak, Glowka, Plesno, Skrzynka, Mielnica) the increase in the concentration of the manganese and iron from outflow to inflow of Charzykowskie lake was found, while the concentration of copper (approx. 4 μg dm⁻³) and cadmium ( < 0.5 μg dm⁻³) was similar in all lakes. The concentration of the lead also varied within 2.1-3.6 μg dm⁻³. The concentration of nickel was approx. 3-fold higher in Ostrowite lake than other lakes of Struga. In turn the waters of the lakes Ostrowite, Jelen and Belczak were rich in zinc. The lowest level of heavy metals was observed in Zielone lake. In the second group of lakes, i.e., Krzywce Wielkie and Krzywce Male the heavy metal concentrations were lower than in the waters of Struga but higher than in oligotrophic lakes, i.e., Nierybno, Gluche, Kociol, Gacno Wielkie, Gacno Mae, Dlugie, Zabionek, and Sosnowek. The concentration of cadmium was below 0.5 μg dm⁻³ in all the studied lakes from this group. In the group of oligotrophic lakes the highest concentrations of metals such as manganese, iron, zinc and nickel in Gacno Male and Gacno Wielkie were observed. The high level of manganese in Sosnowek and Gacno Wielkie lakes was found. The lead level was also high in Nierybno lake and nickel in Gacno Wielkie lake. The lower level of heavy metals was in oligotrophic lakes such as Kociol, Dlugie, Zabionek and α-mesotrophic lake, Krzywce Wielkie. Generally, the level of heavy metals in studied lakes situated in Bory Tucholskie National Park was lower than in other lakes of Bory Tucholskie Biosphere Reserve.

Keywords: Bory Tucholskie Biosphere Reserve, Bory Tucholskie National Park, heavy metals, lakes

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Authors: Wenfa Yu, Thuva Gnanasampanthan, John Finlay, Jessica Clarke, Charlotte Anderson, Tony Clare, Axel Rosenhahn

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Marine biofouling is a worldwide problem at vast economic and ecological costs. Historically it was combated with toxic coatings such as tributyltin. As those coatings being banned nowadays, finding environmental friendly antifouling solution has become an urgent topic. In this study antifouling coatings consisted of natural occurring polysaccharides hyaluronic acid (HA), alginic acid (AA), chitosan (Ch) and polyelectrolyte polyethylenimine (PEI) are constructed into polyelectrolyte multilayers (PEMs) in a Layer-by-Layer (LbL) method. LbL PEM construction is a straightforward way to assemble biomacromolecular coatings on surfaces. Advantages about PEM include ease of handling, highly diverse PEM composition, precise control over the thickness and so on. PEMs have been widely employed in medical application and there are numerous studies regarding their protein adsorption, elasticity and cell adhesive properties. With the adjustment of coating composition, termination layer charge, coating morphology and cross-linking method, it is possible to prepare low marine biofouling coatings with PEMs. In this study, using spin coating technology, PEM construction was achieved at smooth multilayers with roughness as low as 2nm rms and highly reproducible thickness around 50nm. To obtain stability in sea water, the multilayers were covalently cross-linked either thermally or chemically. The cross-linking method affected surface energy, which was reflected in water contact angle, thermal cross-linking led to hydrophobic surfaces and chemical cross-linking generated hydrophilic surfaces. The coatings were then evaluated regarding its protein resistance and biological species resistance. While the hydrophobic thermally cross-linked PEM had low resistance towards proteins, the resistance of chemically cross-linked PEM strongly depended on the PEM termination layer and the charge of the protein, opposite charge caused high adsorption and same charge low adsorption, indicating electrostatic interaction plays a crucial role in the protein adsorption processes. Ulva linza was chosen as the biological species for antifouling performance evaluation. Despite of the poor resistance towards protein adsorption, thermally cross-linked PEM showed good resistance against Ulva spores settlement, the chemically cross-linked multilayers showed poor resistance regardless of the termination layer. Marine species adhesion is a complex process, although it involves proteins as bioadhesives, protein resistance its own is not a fully indicator for its antifouling performance. The species will pre select the surface, responding to cues like surface energy, chemistry, or charge and so on. Thus making it difficult for one single factors to determine its antifouling performance. Preparing PEM coating is a comprehensive work involving choosing polyelectrolyte combination, determining termination layer and the method for cross-linking. These decisions will affect PEM properties such as surface energy, charge, which is crucial, since biofouling is a process responding to surface properties in a highly sensitive and dynamic way.

Keywords: hyaluronic acid, polyelectrolyte multilayers, protein resistance, Ulva linza zoospores

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Authors: David Abrahams

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In October 2016 South Africa deposited its ‘instrument of withdrawal’ from the Rome Statute of the International Criminal Court, with the Secretary-General of the United Nations. The Rome Statute is the founding document of the treaty-based International Criminal Court (ICC). The ICC has jurisdiction to hear cases where crimes against humanity, war crimes and genocide have been committed, on the basis of individual criminal responsibility. It is therefore not surprising that one of the ICCs mandates is to ensure that the sufferings, due to gross human rights violations towards the civilian population is, in principle, brought to an end by punishing those individuals responsible, thus providing justice to the victims. The ICC is unable to effectively fulfill its mandate and thus depends, in part on the willingness of states to assist the Court in its functions. This requires states to ratify the Statute and to domesticate its provisions, depending on whether it is a monist or dualist state. South Africa ratified the Statute in November 2000, and domesticated the Statute in 2002 by virtue of the Implementation of the Rome Statute of the International Criminal Court Act 27 of 2002. South Africa thus remains under an obligation to cooperate with the ICC until the final date of withdrawal, which is October 2017. An AU Summit was hosted by South Africa during June 2015. Omar Al-Bashir, whom the prosecutor of the ICC has indicted on two separate occasions, was invited to the summit. South Africa made an agreement with the AU that it will honour its obligations in terms of its Diplomatic and Immunities Privileges Act of 2001, by granting immunity to all heads of state, including that of Sudan. This decision by South Africa has raised a plethora of questions regarding the status and hierarchy of international laws versus regional laws versus domestic laws. In particular, this paper explores whether a state’s international law treaty obligations may be suspended in favour of, firstly, regional peace (thus safeguarding the security of the civilian population against further atrocities and other gross violations of human rights), and secondly, head of state immunity. This paper also reflects on the effectiveness of the trias politca in South Africa in relation the manner in which South African courts have confirmed South Africa’s failure in fulfilling its obligations in terms of the Rome Statute. A secondary question which will also be explored, is whether the Rome Statute is currently an effective tool in dealing with gross violations of human rights, particularly in a regional African context, given the desire by a number of African states currently party to the Statute, to engage in a mass exodus from the Statute. Finally, the paper concludes with a proposal that there can be no justice for victims of gross human rights violations unless states are serious in playing an instrumental role in bringing an end to impunity in Africa, and that withdrawing from the ICC without an alternative, effective system in place, will simply perpetuate impunity.

Keywords: African Union, diplomatic immunity, impunity, international criminal court, South Africa

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Authors: Welder A. Baldassini, Jon J. Ramsey, Marcos R. Chiaratti, Amália S. Chaves, Renata H. Branco, Sarah F. M. Bonilha, Dante P. D. Lanna

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With increased production costs there is a need for animals that are more efficient in terms of meat production. In this context, the role of mitochondrial DNA (mtDNA) on physiological processes in liver, muscle and adipose tissues may account for inter-animal variation in energy expenditures and heat production. The purpose this study was to investigate if the amounts of mtDNA in liver, muscle and adipose tissue (subcutaneous and visceral depots) of Nellore bulls are associated with residual feed intake (RFI) and estimated heat production (EHP). Eighteen animals were individually fed in a feedlot for 90 days. RFI values were obtained by regression of dry matter intake (DMI) in relation to average daily gain (ADG) and mid-test metabolic body weight (BW). The animals were classified into low (more efficient) and high (less efficient) RFI groups. The bulls were then randomly distributed in individual pens where they were given excess feed twice daily to result in 5 to 10% orts for 90 d with diet containing 15% crude protein and 2.7 Mcal ME/kg DM. The heart rate (HR) of bulls was monitored for 4 consecutive days and used for calculation of EHP. Electrodes were fitted to bulls with stretch belts (POLAR RS400; Kempele, Finland). To calculate oxygen pulse (O2P), oxygen consumption was obtained using a facemask connected to the gas analyzer (EXHALYZER, ECOMedics, Zurich, Switzerland) and HR were simultaneously measured for 15 minutes period. Daily oxygen (O2) consumption was calculated by multiplying the volume of O2 per beat by total daily beats. EHP was calculated multiplying O2P by the average HR obtained during the 4 days, assuming 4.89 kcal/L of O2 to measure daily EHP that was expressed in kilocalories/day/kilogram metabolic BW (kcal/day/kg BW0.75). Blood samples were collected between days 45 and 90th after the beginning of the trial period in order to measure the concentration of hemoglobin and hematocrit. The bulls were slaughtered in an experimental slaughter house in accordance with current guidelines. Immediately after slaughter, a section of liver, a portion of longissimus thoracis (LT) muscle, plus a portion of subcutaneous fat (surrounding LT muscle) and portions of visceral fat (kidney, pelvis and inguinal fat) were collected. Samples of liver, muscle and adipose tissues were used to quantify mtDNA copy number per cell. The number of mtDNA copies was determined by normalization of mtDNA amount against a single copy nuclear gene (B2M). Mean of EHP, hemoglobin and hematocrit of high and low RFI bulls were compared using two-sample t-tests. Additionally, the one-way ANOVA was used to compare mtDNA quantification considering the mains effects of RFI groups. We found lower EHP (83.047 vs. 97.590 kcal/day/kgBW0.75; P < 0.10), hemoglobin concentration (13.533 vs. 15.108 g/dL; P < 0.10) and hematocrit percentage (39.3 vs. 43.6 %; P < 0.05) in low compared to high RFI bulls, respectively, which may be useful traits to identify efficient animals. However, no differences were observed between the mtDNA content in liver, muscle and adipose tissue of Nellore bulls with high and low RFI.

Keywords: bioenergetics, Bos indicus, feed efficiency, mitochondria

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Authors: Baha Eddine Aissou, Aichouche Belhadj Aissa

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Light detection and ranging (LiDAR) is an active remote sensing technology used for several applications. Airborne LiDAR is becoming an important technology for the acquisition of a highly accurate dense point cloud. A classification of airborne laser scanning (ALS) point cloud is a very important task that still remains a real challenge for many scientists. Support vector machine (SVM) is one of the most used statistical learning algorithms based on kernels. SVM is a non-parametric method, and it is recommended to be used in cases where the data distribution cannot be well modeled by a standard parametric probability density function. Using a kernel, it performs a robust non-linear classification of samples. Often, the data are rarely linearly separable. SVMs are able to map the data into a higher-dimensional space to become linearly separable, which allows performing all the computations in the original space. This is one of the main reasons that SVMs are well suited for high-dimensional classification problems. Only a few training samples, called support vectors, are required. SVM has also shown its potential to cope with uncertainty in data caused by noise and fluctuation, and it is computationally efficient as compared to several other methods. Such properties are particularly suited for remote sensing classification problems and explain their recent adoption. In this poster, the SVM classification of ALS LiDAR data is proposed. Firstly, connected component analysis is applied for clustering the point cloud. Secondly, the resulting clusters are incorporated in the SVM classifier. Radial basic function (RFB) kernel is used due to the few numbers of parameters (C and γ) that needs to be chosen, which decreases the computation time. In order to optimize the classification rates, the parameters selection is explored. It consists to find the parameters (C and γ) leading to the best overall accuracy using grid search and 5-fold cross-validation. The exploited LiDAR point cloud is provided by the German Society for Photogrammetry, Remote Sensing, and Geoinformation. The ALS data used is characterized by a low density (4-6 points/m²) and is covering an urban area located in residential parts of the city Vaihingen in southern Germany. The class ground and three other classes belonging to roof superstructures are considered, i.e., a total of 4 classes. The training and test sets are selected randomly several times. The obtained results demonstrated that a parameters selection can orient the selection in a restricted interval of (C and γ) that can be further explored but does not systematically lead to the optimal rates. The SVM classifier with hyper-parameters is compared with the most used classifiers in literature for LiDAR data, random forest, AdaBoost, and decision tree. The comparison showed the superiority of the SVM classifier using parameters selection for LiDAR data compared to other classifiers.

Keywords: classification, airborne LiDAR, parameters selection, support vector machine

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Authors: Pierobon Enrico, Missiaggia Marta, Castelluzzo Michele, Tommasino Francesco, Ricci Leonardo, Scifoni Emanuele, Vincezo Monaco, Boscardin Maurizio, La Tessa Chiara

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Clinical outcomes collected over the past three decades have suggested that ion therapy has the potential to be a treatment modality superior to conventional radiation for several types of cancer, including recurrences, as well as for other diseases. Although the results have been encouraging, numerous treatment uncertainties remain a major obstacle to the full exploitation of particle radiotherapy. To overcome therapy uncertainties optimizing treatment outcome, the best possible radiation quality description is of paramount importance linking radiation physical dose to biological effects. Microdosimetry was developed as a tool to improve the description of radiation quality. By recording the energy deposition at the micrometric scale (the typical size of a cell nucleus), this approach takes into account the non-deterministic nature of atomic and nuclear processes and creates a direct link between the dose deposited by radiation and the biological effect induced. Microdosimeters measure the spectrum of lineal energy y, defined as the energy deposition in the detector divided by most probable track length travelled by radiation. The latter is provided by the so-called “Mean Chord Length” (MCL) approximation, and it is related to the detector geometry. To improve the characterization of the radiation field quality, we define a new quantity replacing the MCL with the actual particle track length inside the microdosimeter. In order to measure this new quantity, we propose a two-stage detector consisting of a commercial Tissue Equivalent Proportional Counter (TEPC) and 4 layers of Low Gain Avalanche Detectors (LGADs) strips. The TEPC detector records the energy deposition in a region equivalent to 2 um of tissue, while the LGADs are very suitable for particle tracking because of the thickness thinnable down to tens of micrometers and fast response to ionizing radiation. The concept of HDM has been investigated and validated with Monte Carlo simulations. Currently, a dedicated readout is under development. This two stages detector will require two different systems to join complementary information for each event: energy deposition in the TEPC and respective track length recorded by LGADs tracker. This challenge is being addressed by implementing SoC (System on Chip) technology, relying on Field Programmable Gated Arrays (FPGAs) based on the Zynq architecture. TEPC readout consists of three different signal amplification legs and is carried out thanks to 3 ADCs mounted on a FPGA board. LGADs activated strip signal is processed thanks to dedicated chips, and finally, the activated strip is stored relying again on FPGA-based solutions. In this work, we will provide a detailed description of HDM geometry and the SoC solutions that we are implementing for the readout.

Keywords: particle tracking, ion therapy, low gain avalanche diode, tissue equivalent proportional counter, microdosimetry

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Authors: Yuan-Jye Tseng, Jia-Shu Li

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To design a product with the given product requirement and design objective, there can be alternative ways to propose the detailed design specifications of the product. In the design modeling stage, alternative design cases with detailed specifications can be modeled to fulfill the product requirement and design objective. Therefore, in the design evaluation stage, it is required to perform an evaluation of the alternative design cases for deciding the final design. The purpose of this research is to develop a product evaluation model for evaluating the alternative design cases by integrated evaluating the criteria of functional design, Kansei design, and design for supply chain. The criteria in the functional design group include primary function, expansion function, improved function, and new function. The criteria in the Kansei group include geometric shape, dimension, surface finish, and layout. The criteria in the design for supply chain group include material, manufacturing process, assembly, and supply chain operation. From the point of view of value and cost, the criteria in the functional design group and Kansei design group represent the design value of the product. The criteria in the design for supply chain group represent the supply chain and manufacturing cost of the product. It is required to evaluate the design value and the supply chain cost to determine the final design. For the purpose of evaluating the criteria in the three criteria groups, a fuzzy analytic network process (FANP) method is presented to evaluate a weighted index by calculating the total relational values among the three groups. A method using the technique for order preference by similarity to ideal solution (TOPSIS) is used to compare and rank the design alternative cases according to the weighted index using the total relational values of the criteria. The final decision of a design case can be determined by using the ordered ranking. For example, the design case with the top ranking can be selected as the final design case. Based on the criteria in the evaluation, the design objective can be achieved with a combined and weighted effect of the design value and manufacturing cost. An example product is demonstrated and illustrated in the presentation. It shows that the design evaluation model is useful for integrated evaluation of functional design, Kansei design, and design for supply chain to determine the best design case and achieve the design objective.

Keywords: design for supply chain, design evaluation, functional design, Kansei design, fuzzy analytic network process, technique for order preference by similarity to ideal solution

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Authors: Hamed Delrobai Ghoochan Atigh

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Androgenic alopecia (AGA) is a common form of hair loss, impacting approximately 50% of females, which leads to reduced self-esteem and quality of life. It causes progressive follicular miniaturization in genetically predisposed individuals. Mesotherapy -- a minimally invasive procedure, topical 2% minoxidil, and oral finasteride have emerged as popular treatment options in the realm of cosmetics. However, the efficacy of mesotherapy compared to other options remains unclear. This study aims to assess the effectiveness of mesotherapy when it is added to topical 2% minoxidil treatment on female androgenic alopecia. Mesotherapy, also known as intradermotherapy, is a technique that entails administering multiple intradermal injections of a carefully composed mixture of compounds in low doses, applied at various points in close proximity to or directly over the affected areas. This study involves a randomized controlled trial with 100 female participants diagnosed with androgenic alopecia. The subjects were randomly assigned to two groups: Group A used topical 2% minoxidil twice daily and took Finastride oral tablet. For Group B, 10 mesotherapy sessions were added to the prior treatment. The injections were administered every week in the first month of treatment, every two weeks in the second month, and after that the injections were applied monthly for four consecutive months. The response assessment was made at baseline, the 4th session, and finally after 6 months when the treatment was complete. Clinical photographs, 7-point Likert scale patient self-evaluation, and 7-point Likert scale assessment tool were used to measure the effectiveness of the treatment. During this evaluation, a significant and visible improvement in hair density and thickness was observed. The study demonstrated a significant increase in treatment efficacy in Group B compared to Group A post-treatment, with no adverse effects. Based on the findings, it appears that mesotherapy offers a significant improvement in female AGA over minoxidil. Hair loss was stopped in Group B after one month and improvement in density and thickness of hair was observed after the third month. The findings from this study provide valuable insights into the efficacy of mesotherapy in treating female androgenic alopecia. Our evaluation offers a detailed assessment of hair growth parameters, enabling a better understanding of the treatments' effectiveness. The potential of this promising technique is significantly enhanced when carried out in a medical facility, guided by appropriate indications and skillful execution. An interesting observation in our study is that in areas where the hair had turned grey, the newly regrown hair does not retain its original grey color; instead, it becomes darker. The results contribute to evidence-based decision-making in dermatological practice and offer different insights into the treatment of female pattern hair loss.

Keywords: androgenic alopecia, female hair loss, mesotherapy, topical 2% minoxidil

Procedia PDF Downloads 102

Authors: Stefan Fuchs

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Against the backdrop of the proliferation of shopping malls in Japan during the last two decades, this paper presents the results of an ethnography conducted at a recently built suburban shopping mall in Western Tokyo. Through the analysis of the lived experiences of local residents, mall customers and the mall management this paper evaluates the benefits and disadvantages of the Business Improvement District (BID) model, which was implemented as urban redevelopment strategy in the area surrounding the shopping mall. The results of this research project show that while the BID model has in some respects contributed to the economic prosperity and to the perceived convenience of the area, it has led to gentrification and the redevelopment shows some deficiencies with regard to the inclusion of the elderly population as well as to the democratization of the decision-making process within the area. In Japan, shopping malls have been steadily growing both in size and number since a series of deregulation policies was introduced in the year 2000 in an attempt to push the domestic economy and to rejuvenate urban landscapes. Shopping malls have thereby become defining spaces of the built environment and are arguably important places of social interaction. Notwithstanding the vital role they play as factors of urban transformation, they have been somewhat overlooked in the research on Japan; especially with respect to their meaning for people’s everyday lives. By examining the ways, people make use of space in a shopping mall the research project presented in this paper addresses this gap in the research. Moreover, the research site of this research project is one of the few BIDs of Japan and the results presented in this paper can give indication on the scope of the future applicability of this urban redevelopment model. The data presented in this research was collected during a nine-months ethnographic fieldwork in and around the shopping mall. This ethnography includes semi-structured interviews with ten key informants as well as direct and participant observations examining the lived experiences and perceptions of people living, shopping or working at the shopping mall. The analysis of the collected data focused on recurring themes aiming at ultimately capturing different perspectives on the same aspects. In this manner, the research project documents the social agency of different groups within one communal network. The analysis of the perceptions towards the urban redevelopment around the shopping mall has shown that mainly the mall customers and large businesses benefit from the BID redevelopment model. While local residents benefit to some extent from their neighbourhood becoming more convenient for shopping they perceive themselves as being disadvantaged by changing demographics due to rising living expenses, the general noise level and the prioritisation of a certain customer segment or age group at the shopping mall. Although the shopping mall examined in this research project is just an example, the findings suggest that in future urban redevelopment politics have to provide incentives for landowners and developing companies to think of other ways of transforming underdeveloped areas.

Keywords: business improvement district, ethnography, shopping mall, urban redevelopment

Procedia PDF Downloads 137

Authors: Anatoliy A. Alabugin, Nikolay K. Topuzov, Sergei V. Aliukov

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It is well known, that while we do a quantitative evaluation of the quality control of some economic processes (in particular, resource saving) with help innovation factors, there are three groups of problems: high uncertainty of indicators of the quality management, their considerable ambiguity, and high costs to provide a large-scale research. These problems are defined by the use of contradictory objectives of enhancing of the quality control in accordance with innovation factors and preservation of economic stability of the enterprise. The most acutely, such factors are felt in the countries lagging behind developed economies of the world according to criteria of innovativeness and effectiveness of management of the resource saving. In our opinion, the following two methods for reconciling of the above-mentioned objectives and reducing of conflictness of the problems are to solve this task most effectively: 1) the use of paradigms and concepts of evolutionary improvement of quality of resource-saving management in the cycle "from the project of an innovative product (technology) - to its commercialization and update parameters of customer value"; 2) the application of the so-called integrative-cyclical approach which consistent with complexity and type of the concept, to studies allowing to get quantitative assessment of the stages of achieving of the consistency of these objectives (from baseline of imbalance, their compromise to achievement of positive synergies). For implementation, the following mathematical tools are included in the integrative-cyclical approach: index-factor analysis (to identify the most relevant factors); regression analysis of relationship between the quality control and the factors; the use of results of the analysis in the model of fuzzy sets (to adjust the feature space); method of non-parametric statistics (for a decision on the completion or repetition of the cycle in the approach in depending on the focus and the closeness of the connection of indicator ranks of disbalance of purposes). The repetition is performed after partial substitution of technical and technological factors ("hard") by management factors ("soft") in accordance with our proposed methodology. Testing of the proposed approach has shown that in comparison with the world practice there are opportunities to improve the quality of resource-saving management using innovation factors. We believe that the implementation of this promising research, to provide consistent management decisions for reducing the severity of the above-mentioned contradictions and increasing the validity of the choice of resource-development strategies in terms of parameters of quality management and sustainability of enterprise, is perspective. Our existing experience in the field of quality resource-saving management and the achieved level of scientific competence of the authors allow us to hope that the use of the integrative-cyclical approach to the study and evaluation of the resulting and factor indicators will help raise the level of resource-saving characteristics up to the value existing in the developed economies of post-industrial type.

Keywords: integrative-cyclical approach, quality control, evaluation, innovation factors. economic sustainability, innovation cycle of management, disbalance of goals of development

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Authors: Tomohiko Utsuki, Kyoka Sato

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In emergency medicine, it is recognized that brain resuscitation is very important for the reduction of mortality rate and neurological sequelae. Especially, the control of brain temperature (BT), intracranial pressure (ICP), and cerebral blood flow (CBF) are most required for stabilizing brain’s physiological state in the treatment for such as brain injury, stroke, and encephalopathy. However, the manual control of BT, ICP, and CBF frequently requires the decision and operation of medical staff, relevant to medication and the setting of therapeutic apparatus. Thus, the integration and the automation of the control of those is very effective for not only improving therapeutic effect but also reducing staff burden and medical cost. For realizing such integration and automation, a mathematical model of brain physiological state is necessary as the controlled object in simulations, because the performance test of a prototype of the control system using patients is not ethically allowed. A model of cerebral blood circulation has already been constructed, which is the most basic part of brain physiological state. Also, a migration model of extracellular fluid in brain has been constructed, however the condition that the total volume of intracranial cavity is almost changeless due to the hardness of cranial bone has not been considered in that model. Therefore, in this research, the dynamic migration model of extracellular fluid in brain was constructed on the consideration of the changelessness of intracranial cavity’s total volume. This model is connectable to the cerebral blood circulation model. The constructed model consists of fourteen compartments, twelve of which corresponds to perfused area of bilateral anterior, middle and posterior cerebral arteries, the others corresponds to cerebral ventricles and subarachnoid space. This model enable to calculate the migration of tissue fluid from capillaries to gray matter and white matter, the flow of tissue fluid between compartments, the production and absorption of cerebrospinal fluid at choroid plexus and arachnoid granulation, and the production of metabolic water. Further, the volume, the colloid concentration, and the tissue pressure of/in each compartment are also calculable by solving 40-dimensional non-linear simultaneous differential equations. In this research, the obtained model was analyzed for its validation under the four condition of a normal adult, an adult with higher cerebral capillary pressure, an adult with lower cerebral capillary pressure, and an adult with lower colloid concentration in cerebral capillary. In the result, calculated fluid flow, tissue volume, colloid concentration, and tissue pressure were all converged to suitable value for the set condition within 60 minutes at a maximum. Also, because these results were not conflict with prior knowledge, it is certain that the model can enough represent physiological state of brain under such limited conditions at least. One of next challenges is to integrate this model and the already constructed cerebral blood circulation model. This modification enable to simulate CBF and ICP more precisely due to calculating the effect of blood pressure change to extracellular fluid migration and that of ICP change to CBF.

Keywords: dynamic model, cerebral extracellular migration, brain resuscitation, automatic control

Procedia PDF Downloads 156

Authors: Ezekiel Olukayode Akintunde

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There is a high level of inadequate methods at all levels of food supply in the global food industry. The inadequacies have led to vast wastages of food. Hence there is a need to curb the wastages that can later affect natural resources, water resources, and energy to avoid negative impacts on the climate and the environment. There is a need to engage multifaceted engineering packaging approaches for a sustainable food chain to ensure active packaging, intelligent packaging, new packaging materials, and a sustainable packaging system. Packaging can be regarded as an indispensable component approach that can be applied to solve major problems of sustainable food consumption globally; this is about controlling the environmental impact of packed food. The creative innovation will ensure that packaged foods are free from food-borne diseases and food chemical pollution. This paper evaluates the key shortcomings that must be addressed by innovative food packaging to ensure a safe, natural environment that will preserve energy and sustain water resources. Certain solutions, including fabricating microbial biodegradable chemical compounds/polymers from agro-food waste remnants, appear a bright path to ensure a strong and innovative waste-based food packaging system. Over the years, depletion in the petroleum reserves has brought about the emergence of biodegradable polymers as a proper replacement for traditional plastics; moreover, the increase in the production of traditional plastics has raised serious concerns about environmental threats. Biodegradable polymers have proven to be biocompatible, which can also be processed for other useful applications. Therefore, this study will showcase a workable guiding framework for designing a sustainable food packaging system that will not constitute a danger to our present society and that will surely preserve natural water resources. Various assessment methods will be deployed at different stages of the packaging design to enhance the package's sustainability. Every decision that will be made must be facilitated with methods that will be engaged per stage to allow for corrective measures throughout the cycle of the design process. Basic performance appraisal of packaging innovations. Food wastage can result in inimical environmental impacts, and ethical practices must be carried out for food loss at home. An examination in West Africa quantified preventable food wastage over the entire food value chain at almost 180kg per person per year. That is preventable food wastage, 35% of which originated at the household level. Many food losses reported, which happened at the harvesting, storage, transportation, and processing stages, are not preventable and are without much environmental impact because such wastage can be used for feeding. Other surveys have shown that 15%-20% of household food losses can be traced to food packaging. Therefore, new innovative packaging systems can lessen the environmental effect of food wastage to extend shelf‐life to lower food loss in the process distribution chain and at the household level.

Keywords: food packaging, biodegradable polymer, intelligent packaging, shelf-life

Procedia PDF Downloads 57