Search results for: cone contrast sensitivity

Authors: Natalia C. E. S. Nascimento, Mercia L. Oliveira, Fernando R. A. Lima, Leonardo T. C. do Nascimento, Marina B. Silveira, Brigida G. A. Schirmer, Andrea V. Ferreira, Carlos Malamut, Juliana B. da Silva

Abstract:

Tissue hypoxia is a common characteristic of solid tumors leading to decreased sensitivity to radiotherapy and chemotherapy. In the clinical context, tumor hypoxia assessment employing the positron emission tomography (PET) tracer ¹⁸F-fluoromisonidazole ([¹⁸F]FMISO) is helpful for physicians for planning and therapy adjusting. The aim of this work was to implement the synthesis of 18F-FMISO in a TRACERlab® MXFDG module and also to establish the quality control procedure. [¹⁸F]FMISO was synthesized at Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN/Brazil) using an automated synthesizer (TRACERlab® MXFDG, GE) adapted for the production of [¹⁸F]FMISO. The FMISO chemical standard was purchased from ABX. 18O- enriched water was acquired from Center of Molecular Research. Reagent kits containing eluent solution, acetonitrile, ethanol, 2.0 M HCl solution, buffer solution, water for injections and [¹⁸F]FMISO precursor (dissolved in 2 ml acetonitrile) were purchased from ABX. The [¹⁸F]FMISO samples were purified by Solid Phase Extraction method. The quality requirements of [¹⁸F]FMISO are established in the European Pharmacopeia. According to that reference, quality control of [¹⁸F]FMISO should include appearance, pH, radionuclidic identity and purity, radiochemical identity and purity, chemical purity, residual solvents, bacterial endotoxins, and sterility. The duration of the synthesis process was 53 min, with radiochemical yield of (37.00 ± 0.01) % and the specific activity was more than 70 GBq/µmol. The syntheses were reproducible and showed satisfactory results. In relation to the quality control analysis, the samples were clear and colorless at pH 6.0. The spectrum emission, measured by using a High-Purity Germanium Detector (HPGe), presented a single peak at 511 keV and the half-life, determined by the decay method in an activimeter, was (111.0 ± 0.5) min, indicating no presence of radioactive contaminants, besides the desirable radionuclide (¹⁸F). The samples showed concentration of tetrabutylammonium (TBA) < 50μg/mL, assessed by visual comparison to TBA standard applied in the same thin layer chromatographic plate. Radiochemical purity was determined by high performance liquid chromatography (HPLC) and the results were 100%. Regarding the residual solvents tested, ethanol and acetonitrile presented concentration lower than 10% and 0.04%, respectively. Healthy female mice were injected via lateral tail vein with [¹⁸F]FMISO, microPET imaging studies (15 min) were performed after 2 h post injection (p.i), and the biodistribution was analyzed in five-time points (30, 60, 90, 120 and 180 min) after injection. Subsequently, organs/tissues were assayed for radioactivity with a gamma counter. All parameters of quality control test were in agreement to quality criteria confirming that [¹⁸F]FMISO was suitable for use in non-clinical and clinical trials, following the legal requirements for the production of new radiopharmaceuticals in Brazil.

Keywords: automatic radiosynthesis, hypoxic tumors, pharmacopeia, positron emitters, quality requirements

Procedia PDF Downloads 170

Authors: Aurica P. Chiriac, Vera Balan, Mihai Asandulesa, Elena Butnaru, Nita Tudorachi, Elena Stoleru, Loredana E. Nita, Iordana Neamtu, Alina Diaconu, Liliana Mititelu-Tartau

Abstract:

The interest for studying ‘smart’ materials is entirely justified and in this context were realized investigations on poly(2-hydroxyethylmethacrylate-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane), which is a macromolecular compound with sensibility at pH and temperature, gel formation capacity, binding properties, amphilicity, good oxidative and thermal stability. Physico-chemical characteristics in terms of the molecular weight, temperature-sensitive abilities and thermal stability, as well rheological, dielectric and spectroscopic properties were evaluated in correlation with further coupling capabilities. Differential scanning calorimetry investigation indicated Tg at 36.6 °C and a melting point at Tm=72.8°C, for the studied copolymer, and up to 200oC two exothermic processes (at 99.7°C and 148.8°C) were registered with losing weight of about 4 %, respective 19.27%, which indicate just processes of thermal decomposition (and not phenomena of thermal transition) owing to scission of the functional groups and breakage of the macromolecular chains. At the same time, the rheological studies (rotational tests) confirmed the non-Newtonian shear-thinning fluid behavior of the copolymer solution. The dielectric properties of the copolymer have been evaluated in order to investigate the relaxation processes and two relaxation processes under Tg value were registered and attributed to localized motions of polar groups from side chain macromolecules, or parts of them, without disturbing the main chains. According to literature and confirmed as well by our investigations, β-relaxation is assigned with the rotation of the ester side group and the γ-relaxation corresponds to the rotation of hydroxy- methyl side groups. The fluorescence spectroscopy confirmed the copolymer structure, the spiroacetal moiety getting an axial conformation, more stable, with lower energy, able for specific interactions with molecules from environment, phenomena underlined by different shapes of the emission spectra of the copolymer. Also, the copolymer was used as template for indomethacin incorporation as model drug, and the biocompatible character of the complex was confirmed. The release behavior of the bioactive compound was dependent by the copolymer matrix composition, the increasing of 3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane comonomer amount attenuating the drug release. At the same time, the in vivo studies did not show significant differences of leucocyte formula elements, GOT, GPT and LDH levels, nor immune parameters (OC, PC, and BC) between control mice group and groups treated just with copolymer samples, with or without drug, data attesting the biocompatibility of the polymer samples. The investigation of the physico-chemical characteristics of poly(2-hydrxyethyl methacrylate-co-3, 9-divinyl-2, 4, 8, 10-tetraoxaspiro (5.5) undecane) in terms of temperature-sensitive abilities, rheological and dielectrical properties, are bringing useful information for further specific use of this polymeric compound.

Keywords: bioapplications, dielectric and spectroscopic properties, dual sensitivity at pH and temperature, smart materials

Procedia PDF Downloads 259

Authors: Ippei Sato, Naonori Shibata, Tetsuya Saruwatari, Naruhito Matsumoto

Abstract:

Friction stir welding (FSW) has been widely used in the automotive, aerospace, and high-tech industries due to its superiority in mechanical properties after joining. In order to achieve a good quality joint by friction stir welding (FSW), it is necessary to secure an advanced angle (usually 3 to 5 degrees) using a dedicated FSW machine and to join on a highly rigid machine. On the other hand, although recently, a new combined machine that combines the cutting function of a conventional machining center with the FSW function has appeared on the market, its joining process window is small, so joining defects easily occur, and it lacks reproducibility, which limits its application to the automotive industry, where control accuracy is required. This has limited the use of FSW machines in the automotive industry, where control accuracy is required. FSW-only machines or hybrid equipment that combines FSW and cutting machines require high capital investment costs, which is one of the reasons why FSW itself has not penetrated the market. Synchronized stir welding, a next-generation joining technology developed by our company, requires no tilt angle and is a very cost-effective method of welding. It is a next-generation joining technology that does not require a tilt angle, does not require a complicated spindle mechanism, and minimizes the load and vibration on the spindle, temperature during joining, and shoulder diameter, thereby enabling a wide range of joining conditions and high-strength, high-speed joining with no joining defects. In synchronized stir welding, the tip of the joining tool is "driven by microwaves" in both the rotational and vertical directions of the tool. The tool is synchronized and stirred in the direction and at the speed required by the material to be stirred in response to the movement required by the material to be welded, enabling welding that exceeds conventional concepts. Conventional FSW is passively stirred by an external driving force, resulting in low joining speeds and high heat input due to the need for a large shoulder diameter. In contrast, SSW is characterized by the fact that materials are actively stirred in synchronization with the direction and speed in which they are to be stirred, resulting in a high joining speed and a small shoulder diameter, which allows joining to be completed with low heat input. The advantages of synchronized stir welding technology in terms of basic mechanical properties are described. The superiority of the basic mechanical properties of SSW over FSW was evaluated as a comparison of the strength of the joint cross section in the comparison between FSW and SSW. SSW, compared to FSW, has tensile strength; base metal 242 MPa/217 MPa after FSW 89%, base metal 242 MPa/225 MPa after SSW 93%. Vickers hardness; base metal 75.0HV/FSW; 57.5HV 76% SSW; 66.0HV 88% (weld center), showing excellent results. In the tensile test, the material used was aluminum (A5052-H112) plate 5 mm thick, and the specimen was dumbbell-shaped, 2 mm thick, 4 mm wide, and 60 mm long. Measurements were made at a loading speed of 20%/min (in accordance with Z 2241:2022). Tensile testing machine: INSTRON Japan, model: INSTRON 5982. Vickers hardness was measured on a 5 mm thick specimen of A5052 tempered H112 with a width of 15 mm at 0.3 pitch (in accordance with JIS Z 2244:2020). Vickers tester: FUTURE-TECH Model: FM-300.

Keywords: SSW, synchronized stir welding, high speed welding, low temperature welding, high strength

Procedia PDF Downloads 25

Authors: M. Shahab Uddin, Pennung Warnitchai

Abstract:

Currently more than half of the world’s populations are living in cities, and the number and sizes of cities are growing faster than ever. Cities rely on the effective functioning of complex and interdependent critical infrastructures networks to provide public services, enhance the quality of life, and save the community from hazards and disasters. In contrast, complex connectivity and interdependency among the urban critical infrastructures bring management challenges and make the urban system prone to the domino effect. Unplanned rapid growth, increased connectivity, and interdependency among the infrastructures, resource scarcity, and many other socio-political factors are affecting the typical state of an urban system and making it susceptible to numerous sorts of diversion. In addition to internal vulnerabilities, urban systems are consistently facing external threats from natural and manmade hazards. Cities are not just complex, interdependent system, but also makeup hubs of the economy, politics, culture, education, etc. For survival and sustainability, complex urban systems in the current world need to manage their vulnerabilities and hazardous incidents more wisely and more interactively. Coordinated management in such systems makes for huge potential when it comes to absorbing negative effects in case some of its components were to function improperly. On the other hand, ineffective management during a similar situation of overall disorder from hazards devastation may make the system more fragile and push the system to an ultimate collapse. Following the quantum, the current research hypothesizes that a hazardous event starts its journey as an emergency, and the system’s internal vulnerability and response capacity determine its destination. Connectivity and interdependency among the urban critical infrastructures during this stage may transform its vulnerabilities into dynamic damaging force. An emergency may turn into a disaster in the absence of effective management; similarly, mismanagement or lack of management may lead the situation towards a catastrophe. Situation awareness and factual decision-making is the key to win a battle. The current research proposed a contextual decision support system for an urban critical infrastructure system while integrating three different models: 1) Damage cascade model which demonstrates damage propagation among the infrastructures through their connectivity and interdependency, 2) Restoration model, a dynamic restoration process of individual infrastructure, which is based on facility damage state and overall disruptions in surrounding support environment, and 3) Optimization model that ensures optimized utilization and distribution of available resources in and among the facilities. All three models are tightly connected, mutually interdependent, and together can assess the situation and forecast the dynamic outputs of every input. Moreover, this integrated model will hold disaster managers and decision makers responsible when it comes to checking all the alternative decision before any implementation, and support to produce maximum possible outputs from the available limited inputs. This proposed model will not only support to reduce the extent of damage cascade but will ensure priority restoration and optimize resource utilization through adaptive and collaborative management. Complex systems predictably fail but in unpredictable ways. System understanding, situation awareness, and factual decisions may significantly help urban system to survive and sustain.

Keywords: disaster prevention, decision support system, emergency response, urban critical infrastructure system

Procedia PDF Downloads 195

Authors: Ekta Yadav, Sukanta Bhattacharya, Brijesh Yadav, Ariel Hus, Jagjit Yadav

Abstract:

Background and Significance: Respiratory exposure to toxicants (chemicals or particulates) causes disruption of lung homeostasis leading to lung toxicity/injury manifested as pulmonary inflammation, edema, and/or other effects depending on the type and extent of exposure. This emphasizes the need for investigating toxicant type-specific mechanisms to understand therapeutic targets. Aquaporins, aka water channels, are known to play a role in lung homeostasis. Particularly, the two major lung aquaporins AQP5 and AQP1 expressed in alveolar epithelial and vasculature endothelia respectively allow for movement of the fluid between the alveolar air space and the associated vasculature. In view of this, the current study is focused on understanding the regulation of lung aquaporins and other targets during inhalation exposure to toxic chemicals (Cigarette smoke chemicals) versus toxic particles (Carbon nanoparticles) or co-exposures to understand their relevance as markers of injury and intervention. Methodologies: C57BL/6 mice (5-7 weeks old) were used in this study following an approved protocol by the University of Cincinnati Institutional Animal Care and Use Committee (IACUC). The mice were exposed via oropharyngeal aspiration to multiwall carbon nanotube (MWCNT) particles suspension once (33 ugs/mouse) followed by housing for four weeks or to Cigarette smoke Extract (CSE) using a daily dose of 30µl/mouse for four weeks, or to co-exposure using the combined regime. Control groups received vehicles following the same dosing schedule. Lung toxicity/injury was assessed in terms of homeostasis changes in the lung tissue and lumen. Exposed lungs were analyzed for transcriptional expression of specific targets (AQPs, surfactant protein A, Mucin 5b) in relation to tissue homeostasis. Total RNA from lungs extracted using TRIreagent kit was analyzed using qRT-PCR based on gene-specific primers. Total protein in bronchoalveolar lavage (BAL) fluid was determined by the DC protein estimation kit (BioRad). GraphPad Prism 5.0 (La Jolla, CA, USA) was used for all analyses. Major findings: CNT exposure alone or as co-exposure with CSE increased the total protein content in the BAL fluid (lung lumen rinse), implying compromised membrane integrity and cellular infiltration in the lung alveoli. In contrast, CSE showed no significant effect. AQP1, required for water transport across membranes of endothelial cells in lungs, was significantly upregulated in CNT exposure but downregulated in CSE exposure and showed an intermediate level of expression for the co-exposure group. Both CNT and CSE exposures had significant downregulating effects on Muc5b, and SP-A expression and the co-exposure showed either no significant effect (Muc5b) or significant downregulating effect (SP-A), suggesting an increased propensity for infection in the exposed lungs. Conclusions: The current study based on the lung toxicity mouse model showed that both toxicant types, particles (CNT) versus chemicals (CSE), cause similar downregulation of lung innate defense targets (SP-A, Muc5b) and mostly a summative effect when presented as co-exposure. However, the two toxicant types show differential induction of aquaporin-1 coinciding with the corresponding differential damage to alveolar integrity (vascular permeability). Interestingly, this implies the potential of AQP1 as a differential marker of toxicant type-specific lung injury.

Keywords: aquaporin, gene expression, lung injury, toxicant exposure

Procedia PDF Downloads 154

Authors: Hsien-Te Lin

Abstract:

The purpose of this paper is to introduce the BCFES (building carbon footprint evaluation system), which is a LCA (life cycle assessment) tool developed by the Low Carbon Building Alliance (LCBA) in Taiwan. A qualified BCFES for the building industry should fulfill the function of evaluating carbon footprint throughout all stages in the life cycle of building projects, including the production, transportation and manufacturing of materials, construction, daily energy usage, renovation and demolition. However, many existing BCFESs are too complicated and not very designer-friendly, creating obstacles in the implementation of carbon reduction policies. One of the greatest obstacle is the misapplication of the carbon footprint inventory standards of PAS2050 or ISO14067, which are designed for mass-produced goods rather than building projects. When these product-oriented rules are applied to building projects, one must compute a tremendous amount of data for raw materials and the transportation of construction equipment throughout the construction period based on purchasing lists and construction logs. This verification method is very cumbersome by nature and unhelpful to the promotion of low carbon design. With a view to provide an engineer-oriented BCFE with pre-diagnosis functions, a component input/output (I/O) database system and a scenario simulation method for building energy are proposed herein. Most existing BCFESs base their calculations on a product-oriented carbon database for raw materials like cement, steel, glass, and wood. However, data on raw materials is meaningless for the purpose of encouraging carbon reduction design without a feedback mechanism, because an engineering project is not designed based on raw materials but rather on building components, such as flooring, walls, roofs, ceilings, roads or cabinets. The LCBA Database has been composited from existing carbon footprint databases for raw materials and architectural graphic standards. Project designers can now use the LCBA Database to conduct low carbon design in a much more simple and efficient way. Daily energy usage throughout a building's life cycle, including air conditioning, lighting, and electric equipment, is very difficult for the building designer to predict. A good BCFES should provide a simplified and designer-friendly method to overcome this obstacle in predicting energy consumption. In this paper, the author has developed a simplified tool, the dynamic Energy Use Intensity (EUI) method, to accurately predict energy usage with simple multiplications and additions using EUI data and the designed efficiency levels for the building envelope, AC, lighting and electrical equipment. Remarkably simple to use, it can help designers pre-diagnose hotspots in building carbon footprint and further enhance low carbon designs. The BCFES-LCBA offers the advantages of an engineer-friendly component I/O database, simplified energy prediction methods, pre-diagnosis of carbon hotspots and sensitivity to good low carbon designs, making it an increasingly popular carbon management tool in Taiwan. To date, about thirty projects have been awarded BCFES-LCBA certification and the assessment has become mandatory in some cities.

Keywords: building carbon footprint, life cycle assessment, energy use intensity, building energy

Procedia PDF Downloads 119

Authors: Asim Abbasi, Muhammad Sufyan, Iqra, Hafiza Javaria Ashraf

Abstract:

The share of vector-borne diseases (VBDs) in the global burden of infectious diseases is almost 17%. The advent of new drugs and latest research in medical science helped mankind to compete with these lethal diseases but still diseases transmitted by different mosquito species, including filariasis, malaria, viral encephalitis and dengue are serious threats for people living in disease endemic areas. Injudicious and repeated use of pesticides posed selection pressure on mosquitoes leading to development of resistance. Hence biological control agents are under serious consideration of scientific community to be used in vector control programmes. Fish have a history of predating immature stages of different aquatic insects including mosquitoes. The noteworthy examples in Africa and Asia includes, Aphanius discolour and a fish in the Panchax group. Moreover, common mosquito fish, Gambusia affinis predates mostly on temporary water mosquitoes like anopheline as compared to permanent water breeders like culicines. Mosquitoes belonging to genus Toxorhynchites have a worldwide distribution and are mostly associated with the predation of other mosquito larvae habituating with them in natural and artificial water containers. These species are harmless to humans as their adults do not suck human blood but feeds on floral nectar. However, their activity is mostly temperature dependent as Toxorhynchites brevipalpis consume 359 Aedes aegypti larvae at 30-32 ºC in contrast to 154 larvae at 20-26 ºC. Although many bacterial species were isolated from mosquito cadavers but those belonging to genus Bacillus are found highly pathogenic against them. The successful species of this genus include Bacillus thuringiensis and Bacillus sphaericus. The prime targets of B. thuringiensis are mostly the immatures of genus Aedes, Culex, Anopheles and Psorophora while B. sphaericus is specifically toxic against species of Culex, Psorophora and Culiseta. The entomopathogenic nematodes belonging to family, mermithidae are also pathogenic to different mosquito species. Eighty different species of mosquitoes including Anopheles, Aedes and Culex proved to be highly vulnerable to the attack of two mermithid species, Romanomermis culicivorax and R. iyengari. Cytoplasmic polyhedrosis virus was the first described pathogenic virus, isolated from the cadavers of mosquito specie, Culex tarsalis. Other viruses which are pathogenic to culicine includes, iridoviruses, cytopolyhedrosis viruses, entomopoxviruses and parvoviruses. Protozoa species belonging to division microsporidia are the common pathogenic protozoans in mosquito populations which kill their host by the chronic effects of parasitism. Moreover, due to their wide prevalence in anopheline mosquitoes and transversal and horizontal transmission from infected to healthy host, microsporidia of the genera Nosema and Amblyospora have received much attention in various mosquito control programmes. Fungal based mycopesticides are used in biological control of insect pests with 47 species reported virulent against different stages of mosquitoes. These include both aquatic fungi i.e. species of Coelomomyces, Lagenidium giganteum and Culicinomyces clavosporus, and the terrestrial fungi Metarhizium anisopliae and Beauveria bassiana. Hence, it was concluded that the integrated use of all these biological control agents can be a healthy contribution in mosquito control programmes and become a dire need of the time to avoid repeated use of pesticides.

Keywords: entomopathogenic nematodes, protozoa, Toxorhynchites, vector-borne

Procedia PDF Downloads 239

Authors: Mariia V. Efremova, Iana O. Tcareva, Anastasia D. Blokhina, Ivan S. Grebennikov, Anastasia S. Garanina, Maxim A. Abakumov, Yury I. Golovin, Alexander G. Savchenko, Alexander G. Majouga, Natalya L. Klyachko

Abstract:

During last decades magnetite nanoparticles (NPs) attract a deep interest of scientists due to their potential application in therapy and diagnostics. However, magnetite nanoparticles are toxic and non-stable in physiological conditions. To solve these problems, we decided to create two types of hybrid systems based on magnetite and gold which is inert and biocompatible: gold as a shell material (first type) and gold as separate NPs interfacially bond to magnetite NPs (second type). The synthesis of the first type hybrid nanoparticles was carried out as follows: Magnetite nanoparticles with an average diameter of 9±2 nm were obtained by co-precipitation of iron (II, III) chlorides then they were covered with gold shell by iterative reduction of hydrogen tetrachloroaurate with hydroxylamine hydrochloride. According to the TEM, ICP MS and EDX data, final nanoparticles had an average diameter of 31±4 nm and contained iron even after hydrochloric acid treatment. However, iron signals (K-line, 7,1 keV) were not localized so we can’t speak about one single magnetic core. Described nanoparticles covered with mercapto-PEG acid were non-toxic for human prostate cancer PC-3/ LNCaP cell lines (more than 90% survived cells as compared to control) and had high R2-relaxivity rates (>190 mМ-1s-1) that exceed the transverse relaxation rate of commercial MRI-contrasting agents. These nanoparticles were also used for chymotrypsin enzyme immobilization. The effect of alternating magnetic field on catalytic properties of chymotrypsin immobilized on magnetite nanoparticles, notably the slowdown of catalyzed reaction at the level of 35-40 % was found. The synthesis of the second type hybrid nanoparticles also involved two steps. Firstly, spherical gold nanoparticles with an average diameter of 9±2 nm were synthesized by the reduction of hydrogen tetrachloroaurate with oleylamine; secondly, they were used as seeds during magnetite synthesis by thermal decomposition of iron pentacarbonyl in octadecene. As a result, so-called dumbbell-like structures were obtained where magnetite (cubes with 25±6 nm diagonal) and gold nanoparticles were connected together pairwise. By HRTEM method (first time for this type of structure) an epitaxial growth of magnetite nanoparticles on gold surface with co-orientation of (111) planes was discovered. These nanoparticles were transferred into water by means of block-copolymer Pluronic F127 then loaded with anti-cancer drug doxorubicin and also PSMA-vector specific for LNCaP cell line. Obtained nanoparticles were found to have moderate toxicity for human prostate cancer cells and got into the intracellular space after 45 minutes of incubation (according to fluorescence microscopy data). These materials are also perspective from MRI point of view (R2-relaxivity rates >70 mМ-1s-1). Thereby, in this work magnetite-gold hybrid nanoparticles, which have a strong potential for biomedical application, particularly in targeted drug delivery and magnetic resonance imaging, were synthesized and characterized. That paves the way to the development of special medicine types – theranostics. The authors knowledge financial support from Ministry of Education and Science of the Russian Federation (14.607.21.0132, RFMEFI60715X0132). This work was also supported by Grant of Ministry of Education and Science of the Russian Federation К1-2014-022, Grant of Russian Scientific Foundation 14-13-00731 and MSU development program 5.13.

Keywords: drug delivery, magnetite-gold, MRI contrast agents, nanoparticles, toxicity

Procedia PDF Downloads 354

Authors: Rajeswari Raguraman, Sowmya Parameswaran, Krishnakumar Subramanian, Jagat Kanwar, Rupinder Kanwar

Abstract:

Background: Tumor microenvironment has been implicated in several cancers to regulate cell growth, invasion and metastasis culminating in outcome of therapy. Tumor stroma consists of multiple cell types that are in constant cross-talk with the tumor cells to favour a pro-tumorigenic environment. Not much is known about the existence of tumor microenvironment in the pediatric intraocular malignancy, Retinoblastoma (RB). In the present study, we aim to understand the multiple stromal cellular subtypes and tumor stromal interactions expressed in RB tumors. Materials and Methods: Immunohistochemistry for stromal cell markers CD31, CD68, alpha-smooth muscle (α-SMA), vimentin and glial fibrillary acidic protein (GFAP) was performed on formalin fixed paraffin embedded tissues sections of RB (n=12). The differential expression of stromal target molecules; fibroblast activation protein (FAP), tenascin-C (TNC), osteopontin (SPP1), bone marrow stromal antigen 2 (BST2), stromal derived factor 2 and 4 (SDF2 and SDF4) in primary RB tumors (n=20) and normal retina (n=5) was studied by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting. The differential expression was correlated with the histopathological features of RB. The interaction between RB cell lines (Weri-Rb-1, NCC-RbC-51) and Bone marrow stromal cells (BMSC) was also studied using direct co-culture and indirect co-culture methods. The functional effect of the co-culture methods on the RB cells was evaluated by invasion and proliferation assays. Global gene expression was studied by using Affymetrix 3’ IVT microarray. Pathway prediction was performed using KEGG and the key molecules were validated using qRT-PCR. Results: The immunohistochemistry revealed the presence of several stromal cell types such as endothelial cells (CD31+;Vim+/-); macrophages (CD68+;Vim+/-); Fibroblasts (Vim+; CD31-;CD68- );myofibroblasts (α-SMA+/ Vim+) and invading retinal astrocytes/ differentiated retinal glia (GFAP+; Vim+). A characteristic distribution of these stromal cell types was observed in the tumor microenvironment, with endothelial cells predominantly seen in blood vessels and macrophages near actively proliferating tumor or necrotic areas. Retinal astrocytes and glia were predominant near the optic nerve regions in invasive tumors with sparse distribution in tumor foci. Fibroblasts were widely distributed with rare evidence of myofibroblasts in the tumor. Both gene and protein expression revealed statistically significant (P<0.05) up-regulation of FAP, TNC and BST2 in primary RB tumors compared to the normal retina. Co-culture of BMSC with RB cells promoted invasion and proliferation of RB cells in direct and indirect contact methods respectively. Direct co-culture of RB cell lines with BMSC resulted in gene expression changes in ECM-receptor interaction, focal adhesion, IL-8 and TGF-β signaling pathways associated with cancer. In contrast, various metabolic pathways such a glucose, fructose and amino acid metabolism were significantly altered under the indirect co-culture condition. Conclusion: The study suggests that the close interaction between RB cells and the stroma might be involved in RB tumor invasion and progression which is likely to be mediated by ECM-receptor interactions and secretory factors. Targeting the tumor stroma would be an attractive option for redesigning treatment strategies for RB.

Keywords: gene expression profiles, retinoblastoma, stromal cells, tumor microenvironment

Procedia PDF Downloads 358

Authors: Rana Mohamed, Ahmed E. Gomaa, Gehan Safwat, Ayman Diab

Abstract:

Background: Bio-fabrication is a multidisciplinary research field that combines several principles, fabrication techniques, and protocols from different fields. The open-source-software movement is a movement that supports the use of open-source licenses for some or all software as part of the broader notion of open collaboration. Additive manufacturing is the concept of 3D printing, where it is a manufacturing method through adding layer-by-layer using computer-aided designs (CAD). There are several types of AM system used, and they can be categorized by the type of process used. One of these AM technologies is Digital light processing (DLP) which is a 3D printing technology used to rapidly cure a photopolymer resin to create hard scaffolds. DLP uses a projected light source to cure (Harden or crosslinking) the entire layer at once. Current applications of DLP are focused on dental and medical applications. Other developments have been made in this field, leading to the revolutionary field 3D bioprinting. The open-source movement was started to spread the concept of open-source software to provide software or hardware that is cheaper, reliable, and has better quality. Objective: Modification of desktop 3D printer into 3D bio-printer and the integration of DLP technology and bio-fabrication to produce an antibacterial dental model. Method: Modification of a desktop 3D printer into a 3D bioprinter. Gelatin hydrogel and sodium alginate hydrogel were prepared with different concentrations. Rhizome of Zingiber officinale, Flower buds of Syzygium aromaticum, and Bulbs of Allium sativum were extracted, and extractions were selected on different levels (Powder, aqueous extracts, total oils, and Essential oils) prepared for antibacterial bioactivity. Agar well diffusion method along with the E. coli have been used to perform the sensitivity test for the antibacterial activity of the extracts acquired by Zingiber officinale, Syzygium aromaticum, and Allium sativum. Lastly, DLP printing was performed to produce several dental models with the natural extracted combined with hydrogel to represent and simulate the Hard and Soft tissues. Result: The desktop 3D printer was modified into 3D bioprinter using open-source software Marline and modified custom-made 3D printed parts. Sodium alginate hydrogel and gelatin hydrogel were prepared at 5% (w/v), 10% (w/v), and 15%(w/v). Resin integration with the natural extracts of Rhizome of Zingiber officinale, Flower buds of Syzygium aromaticum, and Bulbs of Allium sativum was done following the percentage 1- 3% for each extract. Finally, the Antimicrobial dental model was printed; exhibits the antimicrobial activity, followed by merging with sodium alginate hydrogel. Conclusion: The open-source movement was successful in modifying and producing a low-cost Desktop 3D Bioprinter showing the potential of further enhancement in such scope. Additionally, the potential of integrating the DLP technology with bioprinting is a promising step toward the usage of the antimicrobial activity using natural products.

Keywords: 3D printing, 3D bio-printing, DLP, hydrogel, antibacterial activity, zingiber officinale, syzygium aromaticum, allium sativum, panax ginseng, dental applications

Procedia PDF Downloads 65

Authors: Alok Bapatla, Pamela Lutting, Mariastella Serrano

Abstract:

Background: Irritable Bowel Syndrome (IBS) is a functional gastrointestinal disorder characterized by abdominal pain associated with altered bowel habits in the absence of an underlying organic cause. Although the exact etiology of IBS is not fully understood, one of the leading theories postulates a pathology within the Brain-Gut Axis that leads to an overall increase in gastrointestinal sensitivity and pejorative changes in gastrointestinal motility. Research and clinical practice have shown that Gut Directed Hypnotherapy (GDH) has a beneficial clinical role in improving Mind-Gut control and thereby comorbid conditions such as anxiety, abdominal pain, constipation, and diarrhea. Aims: This study presents a 17-year old male with underlying anxiety and a one-year history of IBS-Constipation Predominant Subtype (IBS-C), who has demonstrated impressive improvement of symptoms following GDH treatment following refractory trials with medications including bisacodyl, senna, docusate, magnesium citrate, lubiprostone, linaclotide. Method: The patient was referred to a licensed clinical psychologist specializing in clinical hypnosis and cognitive-behavioral therapy (CBT), who implemented “The Standardized Hypnosis Protocol for IBS” developed by Dr. Olafur S. Palsson, Psy.D at the University of North Carolina at Chapel Hill. The hypnotherapy protocol consisted of a total of seven weekly 45-minute sessions supplemented with a 20-minute audio recording to be listened to once daily. Outcome variables included the GAD-7, PHQ-9 and DCI-2, as well as self-ratings (ranging 0-10) for pain (intensity and frequency), emotional distress about IBS symptoms, and overall emotional distress. All variables were measured at intake prior to administration of the hypnosis protocol and at the conclusion of the hypnosis treatment. A retrospective IBS Questionnaire (IBS Severity Scoring System) was also completed at the conclusion of the GDH treatment for pre-and post-test ratings of clinical symptoms. Results: The patient showed improvement in all outcome variables and self-ratings, including abdominal pain intensity, frequency of abdominal pain episodes, emotional distress relating to gut issues, depression, and anxiety. The IBS Questionnaire showed a significant improvement from a severity score of 400 (defined as severe) prior to GDH intervention compared to 55 (defined as complete resolution) at four months after the last session. IBS Questionnaire subset questions that showed a significant score improvement included abdominal pain intensity, days of pain experienced per 10 days, satisfaction with bowel habits, and overall interference of life affected by IBS symptoms. Conclusion: This case supports the existing research literature that GDH has a significantly beneficial role in improving symptoms in patients with IBS. Emphasis is placed on the numerical results of the IBS Questionnaire scoring, which reflects a patient who initially suffered from severe IBS with failed response to multiple medications, who subsequently showed full and sustained resolution

Keywords: pediatrics, constipation, irritable bowel syndrome, hypnotherapy, gut-directed hypnosis

Procedia PDF Downloads 169

Authors: Vitaliy Petrov, Natalia Shusharina, Vitaliy Kasymov, Maksim Patrushev, Evgeny Bogdanov

Abstract:

The leading worldwide death reasons are ischemic heart disease and other cardiovascular illnesses. Generally, the common symptom is high blood pressure. Long-time blood pressure control is very important for the prophylaxis, correct diagnosis and timely therapy. Non-invasive methods which are based on Korotkoff sounds are impossible to apply often and for a long time. Implantable devices can combine longtime monitoring with high accuracy of measurements. The main purpose of this work is to create a real-time monitoring system for decreasing the death rate from cardiovascular diseases. These days implantable electronic devices began to play an important role in medicine. Usually implantable devices consist of a transmitter, powering which could be wireless with a special made battery and measurement circuit. Common problems in making implantable devices are short lifetime of the battery, big size and biocompatibility. In these work, blood pressure measure will be the focus because it’s one of the main symptoms of cardiovascular diseases. Our device will consist of three parts: the implantable pressure sensor, external transmitter and automated workstation in a hospital. The Implantable part of pressure sensors could be based on piezoresistive or capacitive technologies. Both sensors have some advantages and some limitations. The Developed circuit is based on a small capacitive sensor which is made of the technology of microelectromechanical systems (MEMS). The Capacitive sensor can provide high sensitivity, low power consumption and minimum hysteresis compared to the piezoresistive sensor. For this device, it was selected the oscillator-based circuit where frequency depends from the capacitance of sensor hence from capacitance one can calculate pressure. The external device (transmitter) used for wireless charging and signal transmission. Some implant devices for these applications are passive, the external device sends radio wave signal on internal LC circuit device. The external device gets reflected the signal from the implant and from a change of frequency is possible to calculate changing of capacitance and then blood pressure. However, this method has some disadvantages, such as the patient position dependence and static using. Developed implantable device doesn’t have these disadvantages and sends blood pressure data to the external part in real-time. The external device continuously sends information about blood pressure to hospital cloud service for analysis by a physician. Doctor’s automated workstation at the hospital also acts as a dashboard, which displays actual medical data of patients (which require attention) and stores it in cloud service. Usually, critical heart conditions occur few hours before heart attack but the device is able to send an alarm signal to the hospital for an early action of medical service. The system was tested with wireless charging and data transmission. These results can be used for ASIC design for MEMS pressure sensor.

Keywords: MEMS sensor, RF power, wireless data, oscillator-based circuit

Procedia PDF Downloads 559

Authors: Yujie Yuan, Yiyang Fan, Hong Fan

Abstract:

Objective: The RNA methylation recognition protein Aly/REF export factor (ALYREF) is considered one type of “reader” protein acting as a recognition protein of m5C, has been reported involved in several biological progresses including cancer initiation and progression. 5-methylcytosine (m5C) is a conserved and prevalent RNA modification in all species, as accumulating evidence suggests its role in the promotion of tumorigenesis. It has been claimed that ALYREF mediates nuclear export of mRNA with m5C modification and regulates biological effects of cancer cells. However, the systematical regulatory pathways of ALYREF in cancer tissues have not been clarified, yet. Methods: The expression level of ALYREF in pan-cancer and their normal tissues was compared through the data acquired from The Cancer Genome Atlas (TCGA). The University of Alabama at Birmingham Cancer data analysis Portal UALCAN was used to analyze the relationship between ALYREF and clinical pathological features. The relationship between the expression level of ALYREF and prognosis of pan-cancer, and the correlation genes of ALYREF were figured out by using Gene Expression Correlation Analysis database GEPIA. Immune related genes were obtained from TISIDB (an integrated repository portal for tumor-immune system interactions). Immune-related research was conducted by using Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) and TIMER. Results: Based on the data acquired from TCGA, ALYREF has an obviously higher-level expression in various types of cancers compared with relevant normal tissues excluding thyroid carcinoma and kidney chromophobe. The immunohistochemical images on The Human Protein Atlas showed that ALYREF can be detected in cytoplasm, membrane, but mainly located in nuclear. In addition, a higher expression level of ALYREF in tumor tissue generates a poor prognosis in majority of cancers. According to the above results, cancers with a higher expression level of ALYREF compared with normal tissues and a significant correlation between ALYREF and prognosis were selected for further analysis. By using TISIDB, we found that portion of ALYREF co-expression genes (such as BIRC5, H2AFZ, CCDC137, TK1, and PPM1G) with high Pearson correlation coefficient (PCC) were involved in anti-tumor immunity or affect resistance or sensitivity to T cell-mediated killing. Furthermore, based on the results acquired from GEPIA, there was significant correlation between ALYREF and PD-L1. It was exposed that there is a negative correlation between the expression level of ALYREF and ESTIMATE score. Conclusion: The present study indicated that ALYREF plays a vital and universal role in cancer initiation and progression of pan-cancer through regulating mitotic progression, DNA synthesis and metabolic process, and RNA processing. The correlation between ALYREF and PD-L1 implied ALYREF may affect the therapeutic effect of immunotherapy of tumor. More evidence revealed that ALYREF may play an important role in tumor immunomodulation. The correlation between ALYREF and immune cell infiltration level indicated that ALYREF can be a potential therapeutic target. Exploring the regulatory mechanism of ALYREF in tumor tissues may expose the reason for poor efficacy of immunotherapy and offer more directions of tumor treatment.

Keywords: ALYREF, pan-cancer, immunotherapy, PD-L1

Procedia PDF Downloads 39

Authors: Andreia Garrido, Artur Conde, Ana Cunha, Ric De Vos

Abstract:

Climate changes predictions point to increases in abiotic stress for crop plants in Portugal, like pronounced temperature variation and decreased precipitation, which will have negative impact on grapevine physiology and consequently, on grape berry and wine quality. Short-term mitigation strategies have, therefore, been implemented to alleviate the impacts caused by adverse climatic periods. These strategies include foliar application of kaolin, an inert mineral, which has radiation reflection proprieties that decreases stress from excessive heat/radiation absorbed by its leaves, as well as smart irrigation strategies to avoid water stress. However, little is known about the influence of these mitigation measures on grape berries, neither on the photosynthetic activity nor on the photosynthesis-related metabolic profiles of its various tissues. Moreover, the role of fruit photosynthesis on berry quality is poorly understood. The main objective of our work was to assess the effects of kaolin and irrigation treatments on the photosynthetic activity of grape berry tissues (exocarp and seeds) and on their global metabolic profile, also investigating their possible relationship. We therefore collected berries of field-grown plants of the white grape variety Alvarinho from two distinct microclimates, i.e. from clusters exposed to high light (HL, 150 µmol photons m⁻² s⁻¹) and low light (LL, 50 µmol photons m⁻² s⁻¹), from both kaolin and non-kaolin (control) treated plants at three fruit developmental stages (green, véraison and mature). Plant irrigation was applied after harvesting the green berries, which also enabled comparison of véraison and mature berries from irrigated and non-irrigated growth conditions. Photosynthesis was assessed by pulse amplitude modulated chlorophyll fluorescence imaging analysis, and the metabolite profile of both tissues was assessed by complementary metabolomics approaches. Foliar kaolin application resulted in, for instance, an increased photosynthetic activity of the exocarp of LL-grown berries at green developmental stage, as compared to the control non-kaolin treatment, with a concomitant increase in the levels of several lipid-soluble isoprenoids (chlorophylls, carotenoids, and tocopherols). The exocarp of mature berries grown at HL microclimate on kaolin-sprayed non-irrigated plants had higher total sugar levels content than all other treatments, suggesting that foliar application of this mineral results in an increased accumulation of photoassimilates in mature berries. Unbiased liquid chromatography-mass spectrometry-based profiling of semi-polar compounds followed by ASCA (ANOVA simultaneous component analysis) and ANOVA statistical analysis indicated that kaolin had no or inconsistent effect on the flavonoid and phenylpropanoid composition in both seed and exocarp at any developmental stage; in contrast, both microclimate and irrigation influenced the level of several of these compounds depending on berry ripening stage. Overall, our study provides more insight into the effects of mitigation strategies on berry tissue photosynthesis and phytochemistry, under contrasting conditions of cluster light microclimate. We hope that this may contribute to develop sustainable management in vineyards and to maintain grape berries and wines with high quality even at increasing abiotic stress challenges.

Keywords: climate change, grape berry tissues, metabolomics, mitigation strategies

Procedia PDF Downloads 92

Authors: Vinodhini Elangovan, Jen Heng Pek

Abstract:

Background: An ectopic pregnancy is defined as any pregnancy implanted outside of the endometrial cavity. Cornual pregnancy, a rare variety of ectopic pregnancies, is seen in about 2-4% of ectopic pregnancies. It develops in the interstitial portion of the fallopian tube and invades through the uterine wall. This case describes a third-trimester cornual pregnancy that resulted in a uterine rupture. Case: A 38-year old Chinese lady was brought to the Emergency Department (ED) as a standby case for hypotension. She was 30+6 weeks pregnant (Gravida 3, Parous 1). Her past obstetric history included a live birth delivered via lower segment Caesarean section due to non-reassuring fetal status in 2002 and a miscarriage in 2012. She developed generalized abdominal pain. There was no per vaginal bleeding or leaking liquor. There was also no fever, nausea, vomiting, constipation, diarrhea, or urinary symptoms. On arrival in the ED, she was pale, diaphoretic, and lethargic. She had generalized tenderness with guarding and rebound over her abdomen. Point of care ultrasound was performed and showed a large amount of intra-abdominal free fluid, and the fetal heart rate was 170 beats per minute. The point of care hemoglobin was 7.1 g/dL, and lactate was 6.8 mmol/L. The patient’s blood pressure dropped precipitously to 50/36 mmHg, and her heart rate went up to 141 beats per minute. The clinical impression was profound shock secondary to uterine rupture. Intra-operatively, there was extensive haemoperitoneum, and the fetus was seen in the abdominal cavity. The fetus was delivered immediately and handed to the neonatal team. On exploration of the uterus, the point of rupture was at the left cornual region where the placenta was attached to. Discussion: Cornual pregnancies are difficult to diagnose pre-operatively with low ultrasonographic sensitivity and hence are commonly confused with normal intrauterine pregnancies. They pose a higher risk of rupture and hemorrhage compared to other types of ectopic pregnancies. In very rare circumstances, interstitial pregnancies can result in a viable fetus. Uterine rupture resulting in hemorrhagic shock is a true obstetric emergency that can result in significant morbidity and mortality for the patient and the fetus, and early diagnosis in the emergency department is crucial. The patient in this case presented with known risk factors of multiparity, advanced maternal age, and previous lower segment cesarean section, which increased the suspicion of uterine rupture. Ultrasound assessment may be beneficial to any patient who presents with symptoms and a history of uterine surgery to assess the possibility of uterine dehiscence or rupture. Management of a patient suspected of uterine rupture should be systematic in the emergency department and follow an ABC approach. Conclusion: This case demonstrates the importance for an emergency physician to maintain the suspicion for ectopic pregnancy even at advanced gestational ages. It also highlights how even though all emergency physicians may not be qualified to do a detailed pelvic ultrasound, it is essential for them to be competent with a point of care ultrasound to make a prompt diagnosis of conditions such as uterine rupture.

Keywords: cornual ectopic , ectopic pregnancy, emergency medicine, obstetric emergencies

Procedia PDF Downloads 97

Authors: Serap Durkut, A. Eser Elcin, Y. Murat Elcin

Abstract:

Stimuli-sensitive polymeric hydrogels have received extensive attention in the biomedical field due to their sensitivity to physical and chemical stimuli (temperature, pH, ionic strength, light, etc.). This study describes the rheological properties of a novel thermoresponsive poly(N-vinylcaprolactam)-g-collagen hydrogel. In the study, we first synthesized a facile and novel synthetic carboxyl group-terminated thermo-responsive poly(N-vinylcaprolactam)-COOH (PNVCL-COOH) via free radical polymerization. Further, this compound was effectively grafted with native collagen, by utilizing the covalent bond between the carboxylic acid groups at the end of the chains and amine groups of the collagen using cross-linking agent (EDC/NHS), forming PNVCL-g-Col. Newly-formed hybrid hydrogel displayed novel properties, such as increased mechanical strength and thermoresponsive characteristics. PNVCL-g-Col showed low critical solution temperature (LCST) at 38ºC, which is very close to the body temperature. Rheological studies determine structural–mechanical properties of the materials and serve as a valuable tool for characterizing. The rheological properties of hydrogels are described in terms of two dynamic mechanical properties: the elastic modulus G′ (also known as dynamic rigidity) representing the reversible stored energy of the system, and the viscous modulus G″, representing the irreversible energy loss. In order to characterize the PNVCL-g-Col, the rheological properties were measured in terms of the function of temperature and time during phase transition. Below the LCST, favorable interactions allowed the dissolution of the polymer in water via hydrogen bonding. At temperatures above the LCST, PNVCL molecules within PNVCL-g-Col aggregated due to dehydration, causing the hydrogel structure to become dense. When the temperature reached ~36ºC, both the G′ and G″ values crossed over. This indicates that PNVCL-g-Col underwent a sol-gel transition, forming an elastic network. Following temperature plateau at 38ºC, near human body temperature the sample displayed stable elastic network characteristics. The G′ and G″ values of the PNVCL-g-Col solutions sharply increased at 6-9 minute interval, due to rapid transformation into gel-like state and formation of elastic networks. Copolymerization with collagen leads to an increase in G′, as collagen structure contains a flexible polymer chain, which bestows its elastic properties. Elasticity of the proposed structure correlates with the number of intermolecular cross-links in the hydrogel network, increasing viscosity. However, at 8 minutes, G′ and G″ values sharply decreased for pure collagen solutions due to the decomposition of the elastic and viscose network. Complex viscosity is related to the mechanical performance and resistance opposing deformation of the hydrogel. Complex viscosity of PNVCL-g-Col hydrogel was drastically changed with temperature and the mechanical performance of PNVCL-g-Col hydrogel network increased, exhibiting lesser deformation. Rheological assessment of the novel thermo-responsive PNVCL-g-Col hydrogel, exhibited that the network has stronger mechanical properties due to both permanent stable covalent bonds and physical interactions, such as hydrogen- and hydrophobic bonds depending on temperature.

Keywords: poly(N-vinylcaprolactam)-g-collagen, thermoresponsive polymer, rheology, elastic modulus, stimuli-sensitive

Procedia PDF Downloads 219

Authors: Albert W. K. Tan

Abstract:

This research consolidates a comprehensive array of publications from peer-reviewed journals, case studies, and seminar reports focused on reverse logistics and network design. By synthesizing this secondary knowledge, our objective is to identify and articulate key decision factors crucial to reverse logistics network design for e-commerce. Through this exploration, we aim to present a refined mathematical model that offers valuable insights for companies seeking to optimize their reverse logistics operations. The primary goal of this research endeavor is to develop a comprehensive framework tailored to advising organizations and companies on crafting effective networks for their reverse logistics operations, thereby facilitating the achievement of their organizational goals. This involves a thorough examination of various network configurations, weighing their advantages and disadvantages to ensure alignment with specific business objectives. The key objectives of this research include: (i) Identifying pivotal factors pertinent to network design decisions within the realm of reverse logistics across diverse supply chains. (ii) Formulating a structured framework designed to offer informed recommendations for sound network design decisions applicable to relevant industries and scenarios. (iii) Propose a mathematical model to optimize its reverse logistics network. A conceptual framework for designing a reverse logistics network has been developed through a combination of insights from the literature review and information gathered from company websites. This framework encompasses four key stages in the selection of reverse logistics operations modes: (1) Collection, (2) Sorting and testing, (3) Processing, and (4) Storage. Key factors to consider in reverse logistics network design: I) Centralized vs. decentralized processing: Centralized processing, a long-standing practice in reverse logistics, has recently gained greater attention from manufacturing companies. In this system, all products within the reverse logistics pipeline are brought to a central facility for sorting, processing, and subsequent shipment to their next destinations. Centralization offers the advantage of efficiently managing the reverse logistics flow, potentially leading to increased revenues from returned items. Moreover, it aids in determining the most appropriate reverse channel for handling returns. On the contrary, a decentralized system is more suitable when products are returned directly from consumers to retailers. In this scenario, individual sales outlets serve as gatekeepers for processing returns. Considerations encompass the product lifecycle, product value and cost, return volume, and the geographic distribution of returns. II) In-house vs. third-party logistics providers: The decision between insourcing and outsourcing in reverse logistics network design is pivotal. In insourcing, a company handles the entire reverse logistics process, including material reuse. In contrast, outsourcing involves third-party providers taking on various aspects of reverse logistics. Companies may choose outsourcing due to resource constraints or lack of expertise, with the extent of outsourcing varying based on factors such as personnel skills and cost considerations. Based on the conceptual framework, the authors have constructed a mathematical model that optimizes reverse logistics network design decisions. The model will consider key factors identified in the framework, such as transportation costs, facility capacities, and lead times. The authors have employed mixed LP to find the optimal solutions that minimize costs while meeting organizational objectives.

Keywords: reverse logistics, supply chain management, optimization, e-commerce

Procedia PDF Downloads 8

Authors: Daniela Stephanie Kuenstle

Abstract:

Complex industries such as banking or insurance experience slow growth in mobile sales. While today’s mobile applications are sophisticated and enable location based and personalized services, consumers prefer online or even face-to-face services to complete complex transactions. A possible reason for this reluctance is that the provided service within transactional mobile applications (apps) does not adequately correspond to users’ needs. Therefore, this paper examines the impact of the user context on mobile service (m-service) in m-commerce. Motivated by the potential which context-sensitive m-services hold for the future, the impact of temporal variations as a dimension of user context, on m-service design is examined. In particular, the research question asks: Does consumer urgency function as a determinant of m-service composition in transactional apps by moderating the relation between m-service type and m-service success? Thus, the aim is to explore the moderating influence of urgency on m-service types, which includes Technology Mediated Service and Technology Generated Service. While mobile applications generally comprise features of both service types, this thesis discusses whether unexpected urgency changes customer preferences for m-service types and how this consequently impacts the overall m-service success, represented by purchase intention, loyalty intention and service quality. An online experiment with a random sample of N=1311 participants was conducted. Participants were divided into four treatment groups varying in m-service types and urgency level. They were exposed to two different urgency scenarios (high/ low) and two different app versions conveying either technology mediated or technology generated service. Subsequently, participants completed a questionnaire to measure the effectiveness of the manipulation as well as the dependent variables. The research model was tested for direct and moderating effects of m-service type and urgency on m-service success. Three two-way analyses of variance confirmed the significance of main effects, but demonstrated no significant moderation of urgency on m-service types. The analysis of the gathered data did not confirm a moderating effect of urgency between m-service type and service success. Yet, the findings propose an additive effects model with the highest purchase and loyalty intention for Technology Generated Service and high urgency, while Technology Mediated Service and low urgency demonstrate the strongest effect for service quality. The results also indicate an antagonistic relation between service quality and purchase intention depending on the level of urgency. Although a confirmation of the significance of this finding is required, it suggests that only service convenience, as one dimension of mobile service quality, delivers conditional value under high urgency. This suggests a curvilinear pattern of service quality in e-commerce. Overall, the paper illustrates the complex interplay of technology, user variables, and service design. With this, it contributes to a finer-grained understanding of the relation between m-service design and situation dependency. Moreover, the importance of delivering situational value with apps depending on user context is emphasized. Finally, the present study raises the demand to continue researching the impact of situational variables on m-service design in order to develop more sophisticated m-services.

Keywords: mobile consumer behavior, mobile service design, mobile service success, self-service technology, situation dependency, user-context sensitivity

Procedia PDF Downloads 248

Authors: Ruolan Zhang, Ryo Imai, Naoko Senda, Tomoyuki Sakai

Abstract:

Enzymes have attracted increasing attentions in industrial manufacturing for their applicability in catalyzing complex chemical reactions under mild conditions. Directed evolution has become a powerful approach to optimize enzymes and exploit their full potentials under the circumstance of insufficient structure-function knowledge. With the incorporation of cell-free synthetic biotechnology, rapid enzyme synthesis can be realized because no cloning procedure such as transfection is needed. Its open environment also enables direct enzyme measurement. These properties of cell-free biotechnology lead to excellent throughput of enzymes generation. However, the capabilities of current screening methods have limitations. Fluorescence-based assay needs applicable fluorescent label, and the reliability of acquired enzymatic activity is influenced by fluorescent label’s binding affinity and photostability. To acquire the natural activity of an enzyme, another method is to combine pre-screening step and high-performance liquid chromatography (HPLC) measurement. But its throughput is limited by necessary time investment. Hundreds of variants are selected from libraries, and their enzymatic activities are then identified one by one by HPLC. The turn-around-time is 30 minutes for one sample by HPLC, which limits the acquirable enzyme improvement within reasonable time. To achieve the real high-throughput enzyme screening, i.e., obtain reliable enzyme improvement within reasonable time, a widely applicable high-throughput measurement of enzymatic reactions is highly demanded. Here, a high-throughput screening method using broadband coherent anti-Stokes Raman spectroscopy (CARS) was proposed. CARS is one of coherent Raman spectroscopy, which can identify label-free chemical components specifically from their inherent molecular vibration. These characteristic vibrational signals are generated from different vibrational modes of chemical bonds. With the broadband CARS, chemicals in one sample can be identified from their signals in one broadband CARS spectrum. Moreover, it can magnify the signal levels to several orders of magnitude greater than spontaneous Raman systems, and therefore has the potential to evaluate chemical's concentration rapidly. As a demonstration of screening with CARS, alcohol dehydrogenase, which converts ethanol and nicotinamide adenine dinucleotide oxidized form (NAD+) to acetaldehyde and nicotinamide adenine dinucleotide reduced form (NADH), was used. The signal of NADH at 1660 cm⁻¹, which is generated from nicotinamide in NADH, was utilized to measure the concentration of it. The evaluation time for CARS signal of NADH was determined to be as short as 0.33 seconds while having a system sensitivity of 2.5 mM. The time course of alcohol dehydrogenase reaction was successfully measured from increasing signal intensity of NADH. This measurement result of CARS was consistent with the result of a conventional method, UV-Vis. CARS is expected to have application in high-throughput enzyme screening and realize more reliable enzyme improvement within reasonable time.

Keywords: Coherent Anti-Stokes Raman Spectroscopy, CARS, directed evolution, enzyme screening, Raman spectroscopy

Procedia PDF Downloads 103

Authors: I. Martinez-Conesa, E. Garcia-Meca, M. Barradas-Quiroz

Abstract:

The objective of this study is to assess the impact on earnings management of latest two Hofstede cultural dimensions: long-term orientation and indulgence. Long-term orientation represents the alignment of a society towards the future and indulgence expresses the extent to which a society exhibits willingness, or restrain, to realise their impulses. Additionally, this paper tests if there are relevant differences by testing the moderating role of the legal tradition, Continental versus Anglo-Saxon. Our sample comprises 15 countries: Belgium, Canada, Germany, Spain, France, Great Britain, Hong Kong, India, Japan, Korea, Netherlands, Philippines, Portugal, Sweden, and Thailand, with a total of 12,936 observations from 2003 to 2013. Our results show that managers in countries with high levels of long-term orientation reduce their levels of discretionary accruals. The findings do not confirm the effect of indulgence on earnings management. In addition, our results confirm previous literature regarding the effect of individualism, noting that firms in countries with high levels of collectivism might be more inclined to use earnings discretion to protect the welfare of the collective group of firm stakeholders. Uncertainty avoidance results in downwards earnings management as well as high disclosure, suggesting that less manipulation takes place when transparency is higher. Indulgence is the cultural dimension that confronts wellbeing versus survival; dimension is formulated including happiness, the perception of live control and the importance of leisure. Indulgence shows a weak negative correlation with power distance indicating a slight tendency for more hierarchical societies to be less indulgent. Anglo-Saxon countries are a positive effect of individualism and a negative effect of masculinity, uncertainty avoidance, and disclosure. With respect to continental countries, we can see a significant and positive effect of individualism and a significant and negative effect of masculinity, long-term orientation, and indulgence. Therefore, we observe the negative effect on earnings management provoked by higher disclosure and uncertainty avoidance only happens in Anglo-Saxon countries. Meanwhile, the improvement in reporting quality motivated by higher long-term orientation and higher indulgence is dominant in Continental countries. Our results confirm that there is a moderating effect of the legal system in the association between culture and earnings management. This effect is especially relevant in the dimensions related to uncertainty avoidance, long term orientation, indulgence, and disclosure. The negative effect of long-term orientation on earnings management only happens in those countries set in continental legal systems because of the Anglo-Saxon legal systems is supported by the decisions of the courts and the traditions, so it already has long-term orientation. That does not occur in continental systems, depending mainly of contend of the law. Sensitivity analysis used with Jones modified CP model, Jones Standard model and Jones Standard CP model confirm the robustness of these results. This paper collaborates towards a better understanding on how earnings management, culture and legal systems relate to each other, and contribute to previous literature by examining the influence of the two latest Hofstede’s dimensions not previously studied in papers.

Keywords: Hofstede, long-term-orientation, earnings management, indulgence

Procedia PDF Downloads 206

Authors: Pauline Nyssen, Ange Mouithys-Mickalad, Maryse Hoebeke

Abstract:

Inflammation is a complex physiological phenomenon involving chemical and enzymatic mechanisms. Polymorphonuclear neutrophil leukocytes (PMNs) play an important role by producing reactive oxygen species (ROS) and releasing myeloperoxidase (MPO), a pro-oxidant enzyme. Released both in the phagolysosome and the extracellular medium, MPO produces during its peroxidase and halogenation cycles oxidant species, including hypochlorous acid, involved in the destruction of pathogen agents, like bacteria or viruses. Inflammatory pathologies, like rheumatoid arthritis, atherosclerosis induce an excessive stimulation of the PMNs and, therefore, an uncontrolled release of ROS and MPO in the extracellular medium, causing severe damages to the surrounding tissues and biomolecules such as proteins, lipids, and DNA. The treatment of chronic inflammatory pathologies remains a challenge. For many years, MPO has been used as a target for the development of effective treatments. Numerous studies have been focused on the design of new drugs presenting more efficient MPO inhibitory properties. However, some designed inhibitors can be toxic. An alternative consists of assessing the potential inhibitory action of clinically-known molecules, having antioxidant activity. Propofol, 2,6-diisopropyl phenol, which is used as an intravenous anesthetic agent, meets these requirements. Besides its anesthetic action employed to induce a sedative state during surgery or in intensive care units, propofol and its injectable form Diprivan indeed present antioxidant properties and act as ROS and free radical scavengers. A study has also evidenced the ability of propofol to inhibit the formation of the neutrophil extracellular traps fibers, which are important to trap pathogen microorganisms during the inflammation process. The aim of this study was to investigate the potential inhibitory action mechanism of propofol and Diprivan on MPO activity. To go into the anti-inflammatory action of propofol in-depth, two of its oxidative derivatives, 2,6-diisopropyl-1,4-p-benzoquinone (PPFQ) and 3,5,3’,5’-tetra isopropyl-(4,4’)-diphenoquinone (PPFDQ), were studied regarding their inhibitory action. Specific immunological extraction followed by enzyme detection (SIEFED) and molecular modeling have evidenced the low anti-catalytic action of propofol. Stopped-flow absorption spectroscopy and direct MPO activity analysis have proved that propofol acts as a reversible MPO inhibitor by interacting as a reductive substrate in the peroxidase cycle and promoting the accumulation of redox compound II. Overall, Diprivan exhibited a weaker inhibitory action than the active molecule propofol. In contrast, PPFQ seemed to bind and obstruct the enzyme active site, preventing the trigger of the MPO oxidant cycles. PPFQ induced a better chlorination cycle inhibition at basic and neutral pH in comparison to propofol. PPFDQ did not show any MPO inhibition activity. The three interest molecules have also demonstrated their inhibition ability on an important step of the inflammation pathway, the PMNs superoxide anions production, thanks to EPR spectroscopy and chemiluminescence. In conclusion, propofol presents an interesting immunomodulatory activity by acting as a reductive substrate in the peroxidase cycle of MPO, slowing down its activity, whereas PPFQ acts more as an anti-catalytic substrate. Although PPFDQ has no impact on MPO, it can act on the inflammation process by inhibiting the superoxide anions production by PMNs.

Keywords: Diprivan, inhibitor, myeloperoxidase, propofol, spectroscopy

Procedia PDF Downloads 123

Authors: Vittorio Astarita, Giuseppe Guido, Vincenzo Pasquale Giofre, Alessandro Vitale

Abstract:

Traffic microsimulation has been used extensively to evaluate consequences of different traffic planning and control policies in terms of travel time delays, queues, pollutant emissions, and every other common measured performance while at the same time traffic safety has not been considered in common traffic microsimulation packages as a measure of performance for different traffic scenarios. Vehicle conflict techniques that were introduced at intersections in the early traffic researches carried out at the General Motor laboratory in the USA and in the Swedish traffic conflict manual have been applied to vehicles trajectories simulated in microscopic traffic simulators. The concept is that microsimulation can be used as a base for calculating the number of conflicts that will define the safety level of a traffic scenario. This allows engineers to identify unsafe road traffic maneuvers and helps in finding the right countermeasures that can improve safety. Unfortunately, most commonly used indicators do not consider conflicts between single vehicles and roadside obstacles and barriers. A great number of vehicle crashes take place with roadside objects or obstacles. Only some recent proposed indicators have been trying to address this issue. This paper introduces a new procedure based on the simulation of potential crash events for the evaluation of safety levels in microsimulation traffic scenarios, which takes into account also potential crashes with roadside objects and barriers. The procedure can be used to define new conflict indicators. The proposed simulation procedure generates with the random perturbation of vehicle trajectories a set of potential crashes which can be evaluated accurately in terms of DeltaV, the energy of the impact, and/or expected number of injuries or casualties. The procedure can also be applied to real trajectories giving birth to new surrogate safety performance indicators, which can be considered as “simulation-based”. The methodology and a specific safety performance indicator are described and applied to a simulated test traffic scenario. Results indicate that the procedure is able to evaluate safety levels both at the intersection level and in the presence of roadside obstacles. The procedure produces results that are expressed in the same unity of measure for both vehicle to vehicle and vehicle to roadside object conflicts. The total energy for a square meter of all generated crash can be used and is shown on the map, for the test network, after the application of a threshold to evidence the most dangerous points. Without any detailed calibration of the microsimulation model and without any calibration of the parameters of the procedure (standard values have been used), it is possible to identify dangerous points. A preliminary sensitivity analysis has shown that results are not dependent on the different energy thresholds and different parameters of the procedure. This paper introduces a specific new procedure and the implementation in the form of a software package that is able to assess road safety, also considering potential conflicts with roadside objects. Some of the principles that are at the base of this specific model are discussed. The procedure can be applied on common microsimulation packages once vehicle trajectories and the positions of roadside barriers and obstacles are known. The procedure has many calibration parameters and research efforts will have to be devoted to make confrontations with real crash data in order to obtain the best parameters that have the potential of giving an accurate evaluation of the risk of any traffic scenario.

Keywords: road safety, traffic, traffic safety, traffic simulation

Procedia PDF Downloads 111

Authors: Stephanie Al Otaiba, Kyle Roberts

Abstract:

Background and Significance Globally far too many students read below grade level; thus improving literacy outcomes is vital. Research suggests that non-cognitive factors, including Social and Emotional Learning (SEL) are linked to success in literacy outcomes. Converging evidence exists that early interventions are more effective than later remediation; therefore teachers need strategies to support early literacy while developing students’ SEL and their vocabulary, or language, for learning. This presentation describe findings from a US federally-funded project that trained teachers to provide an evidence-based read-aloud program for young children, using commercially available books with multicultural characters and themes to help their students “GROW”. The five GROW SEL themes include: “I can name my feelings”, “I can learn from my mistakes”, “I can persist”, “I can be kind to myself and others”, and “I can work toward and achieve goals”. Examples of GROW vocabulary (from over 100 words taught across the 5 units) include: emotions, improve, resilient, cooperate, accomplish, responsible, compassion, adapt, achieve, analyze. Methodology This study used a mixed methods research design, with qualitative methods to describe data from teacher feedback surveys (regarding satisfaction, feasibility), observations of fidelity of implementation, and with quantitative methods to assess the effect sizes for student vocabulary growth. GROW Intervention and Teacher Training Procedures Researchers trained classroom teachers to implement GROW. Each thematic unit included four books, vocabulary cards with images of the vocabulary words, and scripted lessons. Teacher training included online and in-person training; researchers incorporated virtual reality videos of instructors with child avatars to model lessons. Classroom teachers provided 2-3 20 min lessons per week ranging from short-term (8 weeks) to longer-term trials for up to 16 weeks. Setting and Participants The setting for the study included two large urban charter schools in the South. Data was collected across two years; during the first year, participants included 7 kindergarten teachers and 108 and the second year involved an additional set of 5 kindergarten and first grade teachers and 65 students. Initial Findings The initial qualitative findings indicate teachers reported the lessons to be feasible to implement and they reported that students enjoyed the books. Teachers found the vocabulary words to be challenging and important. They were able to implement lessons with fidelity. Quantitative analyses of growth for each taught word suggest that students’ growth on taught words ranged from large (ES = .75) to small (<.20). Researchers will contrast the effects for more and less successful books within the GROW units. Discussion and Conclusion It is feasible for teachers of young students to effectively teach SEL vocabulary and themes during shared book reading. Teachers and students enjoyed the books and students demonstrated growth on taught vocabulary. Researchers will discuss implications of the study and about the GROW program for researchers in learning sciences, will describe some limitations about research designs that are inherent in school-based research partnerships, and will provide some suggested directions for future research and practice.

Keywords: early literacy, learning science, language and vocabulary, social and emotional learning, multi-cultural

Procedia PDF Downloads 21

Authors: Michelle Maurer, Antonia Last, Mark S. Gresnigt, Bernhard Hube, Alexander S. Mosig

Abstract:

The intestinal epithelium forms an essential barrier to prevent translocation of microorganisms, toxins or other potentially harmful molecules into the bloodstream. In particular, dendritic cells of the intestinal epithelium orchestrate an adapted response of immune tolerance to commensals and immune defense against invading pathogens. Systemic inflammation is typically associated with a dysregulation of this adapted immune response and is accompanied by a disruption of the epithelial and endothelial gut barrier which enables dissemination of pathogens within the human body. To understand the pathophysiological mechanisms underlying the inflammation-associated gut barrier breakdown, it is crucial to elucidate the complex interplay of the host and the intestinal microbiome. A microfluidically perfused three-dimensional intestine-on-chip model was established to emulate these processes in the presence of immune cells, commensal bacteria, and facultative pathogens. Multi-organ tissue flow (MOTiF) biochips made from polystyrene were used for microfluidic perfusion of the intestinal tissue model. The biochips are composed of two chambers separated by a microporous membrane. Each chamber is connected to inlet and outlet channels allowing independent perfusion of the individual channels and application of microfluidic shear stress. Human umbilical vein endothelial cells (HUVECs), monocyte-derived macrophages and intestinal epithelial cells (Caco-2) were assembled on the biochip membrane. Following 7 – 14 days of growth in the presence of physiological flow conditions, the epithelium was colonized with the commensal bacterium Lactobacillus rhamnosus, while the endothelium was perfused with peripheral blood mononuclear cells (PBMCs). Additionally, L. rhamnosus was co-cultivated with the opportunistic fungal pathogen Candida albicans. Within one week of perfusion, the epithelial cells formed self-organized and well-polarized villus- and crypt-like structures that resemble essential morphological characteristics of the human intestine. Dendritic cells were differentiated in the epithelial tissue that specifically responds to bacterial lipopolysaccharide (LPS) challenge. LPS is well-tolerated at the luminal epithelial side of the intestinal model without signs of tissue damage or induction of an inflammatory response, even in the presence of circulating PBMC at the endothelial lining. In contrast, LPS stimulation at the endothelial side of the intestinal model triggered the release of pro-inflammatory cytokines such as TNF, IL-1β, IL-6, and IL-8 via activation of macrophages residing in the endothelium. Perfusion of the endothelium with PBMCs led to an enhanced cytokine release. L. rhamnosus colonization of the model was tolerated in the immune competent tissue model and was demonstrated to reduce damage induced by C. albicans infection. A microfluidic intestine-on-chip model was developed to mimic a systemic infection with a dysregulated immune response under physiological conditions. The model facilitates the colonization of commensal bacteria and co-cultivation with facultative pathogenic microorganisms. Both, commensal bacteria alone and facultative pathogens controlled by commensals, are tolerated by the host and contribute to cell signaling. The human intestine-on-chip model represents a promising tool to mimic microphysiological conditions of the human intestine and paves the way for more detailed in vitro studies of host-microbiota interactions under physiologically relevant conditions.

Keywords: host-microbiota interaction, immune tolerance, microfluidics, organ-on-chip

Procedia PDF Downloads 107

Authors: Christiane H. Kellner, Sarah Reker

Abstract:

The UN-Convention on the Rights of Persons with Disabilities, which Germany also ratified, postulates the necessity of user-centred design, especially when it comes to evaluating the individual needs and wishes of all citizens. Therefore, a multidimensional approach is required. Based on this insight, the structure of the town-like centre in Schönbrunn - a large residential complex and service provider for persons with disabilities in the outskirts of Munich - will be remodelled to open up the community to all people as well as transform social space. This strategy should lead to more equal opportunities and open the way for a much more diverse community. The research project “Index for participation development and quality of life for persons with disabilities” (TeLe-Index, 2014-2016), which is anchored at the Technische Universität München in Munich and at the Franziskuswerk Schönbrunn supports this transformation process called “Vision 2030”. In this context, we have provided academic supervision and support for three projects (the construction of a new school, inclusive housing for children and teenagers with disabilities and the professionalization of employees using person-centred planning). Since we cannot present all the issues of the umbrella-project within the conference framework, we will be focusing on one sub-project more in-depth, namely “The Person-Centred Think Tank” [Arbeitskreis Personenzentriertes Denken; PZD]. In the context of person-centred thinking (PCT), persons with disabilities are encouraged to (re)gain or retain control of their lives through the development of new choice options and the validation of individual lifestyles. PCT should thus foster and support both participation and quality of life. The project aims to establish PCT as a fundamental approach for both employees and persons with disabilities in the institution through in-house training for the staff and, subsequently, training for users. Hence, for the academic support and supervision team, the questions arising from this venture can be summed up as follows: (1) has PCT already gained a foothold at the Franziskuswerk Schönbrunn? And (2) how does it affect the interaction with persons with disabilities and how does it influence the latter’s everyday life? According to the holistic approach described above, the target groups for this study are both the staff and the users of the institution. Initially, we planned to implement the group discussion method for both target-groups. However, in the course of a pretest with persons with intellectual disabilities, it became clear that this type of interview, with hardly any external structuring, provided only limited feedback. In contrast, when the discussions were moderated, there was more interaction and dialogue between the interlocutors. Therefore, for this target-group, we introduced structured group interviews. The insights we have obtained until now will enable us to present the intermediary results of our evaluation. We analysed and evaluated the group interviews and discussions with the help of qualitative content analysis according to Mayring in order to obtain information about users’ quality of life. We sorted out the statements relating to quality of life obtained during the group interviews into three dimensions: subjective wellbeing, self-determination and participation. Nevertheless, the majority of statements were related to subjective wellbeing and self-determination. Thus, especially the limited feedback on participation clearly demonstrates that the lives of most users do not take place beyond the confines of the institution. A number of statements highlighted the fact that PCT is anchored in the everyday interactions within the groups. However, the implementation and fostering of PCT on a broader level could not be detected and thus remain further aims of the project. The additional interviews we have planned should validate the results obtained until now and open up new perspectives.

Keywords: person-centered thinking, research with persons with disabilities, residential complex and service provider, participation, self-determination.

Procedia PDF Downloads 298

Authors: C. Bel, J. Nevado, F. Ciceri, M. Ropacki, T. Hoffmann, P. Lapunzina, C. Buesa

Abstract:

Background: The Phelan-McDermid syndrome (PMS) is a genetic disorder caused by the deletion of the terminal region of chromosome 22 or mutation of the SHANK3 gene. Shank3 disruption in mice leads to dysfunction of synaptic transmission, which can be restored by epigenetic regulation with both Lysine Specific Demethylase 1 (LSD1) inhibitors. PMS subjects result in a variable degree of intellectual disability, delay or absence of speech, autistic spectrum disorders symptoms, low muscle tone, motor delays and epilepsy. Vafidemstat is an LSD1 inhibitor in Phase II clinical development with a well-established and favorable safety profile, and data supporting the restoration of memory and cognition defects as well as reduction of agitation and aggression in several animal models and clinical studies. Therefore, vafidemstat has the potential to become a first-in-class precision medicine approach to treat PMS patients. Aims: The goal of this research is to perform an observational trial to psychometrically characterize individuals carrying deletions in SHANK3 and build a foundation for subsequent precision psychiatry clinical trials with vafidemstat. Methodology: This study is characterizing the clinical profile of 20 to 40 subjects, > 16-year-old, with genotypically confirmed PMS diagnosis. Subjects will complete a battery of neuropsychological scales, including the Repetitive Behavior Questionnaire (RBQ), Vineland Adaptive Behavior Scales, Escala de Observación para el Diagnostico del Autismo (Autism Diagnostic Observational Scale) (ADOS)-2, the Battelle Developmental Inventory and the Behavior Problems Inventory (BPI). Results: By March 2021, 19 patients have been enrolled. Unsupervised hierarchical clustering of the results obtained so far identifies 3 groups of patients, characterized by different profiles of cognitive and behavioral scores. The first cluster is characterized by low Battelle age, high ADOS and low Vineland, RBQ and BPI scores. Low Vineland, RBQ and BPI scores are also detected in the second cluster, which in contrast has high Battelle age and low ADOS scores. The third cluster is somewhat in the middle for the Battelle, Vineland and ADOS scores while displaying the highest levels of aggression (high BPI) and repeated behaviors (high RBQ). In line with the observation that female patients are generally affected by milder forms of autistic symptoms, no male patients are present in the second cluster. Dividing the results by gender highlights that male patients in the third cluster are characterized by a higher frequency of aggression, whereas female patients from the same cluster display a tendency toward higher repetitive behavior. Finally, statistically significant differences in deletion sizes are detected comparing the three clusters (also after correcting for gender), and deletion size appears to be positively correlated with ADOS and negatively correlated with Vineland A and C scores. No correlation is detected between deletion size and the BPI and RBQ scores. Conclusions: Precision medicine may open a new way to understand and treat Central Nervous System disorders. Epigenetic dysregulation has been proposed to be an important mechanism in the pathogenesis of schizophrenia and autism. Vafidemstat holds exciting therapeutic potential in PMS, and this study will provide data regarding the optimal endpoints for a future clinical study to explore vafidemstat ability to treat shank3-associated psychiatric disorders.

Keywords: autism, epigenetics, LSD1, personalized medicine

Procedia PDF Downloads 139

Authors: Laura Norfolk, Georgina Zimbitas, Jan Sefcik, Sarah Staniland

Abstract:

Magnetite nanoparticles (MNP) have been an area of increasing research interest due to their extensive applications in industry, such as in carbon capture, water purification, and crucially, the biomedical industry. The use of MNP in the biomedical industry is rising, with studies on their effect as Magnetic resonance imaging contrast agents, drug delivery systems, and as hyperthermic cancer treatments becoming prevalent in the nanomaterial research community. Particles used for biomedical purposes must meet stringent criteria; the particles must have consistent shape and size between particles. Variation between particle morphology can drastically alter the effective surface area of the material, making it difficult to correctly dose particles that are not homogeneous. Particles of defined shape such as octahedral and cubic have been shown to outperform irregular shaped particles in some applications, leading to the need to synthesize particles of defined shape. In nature, highly homogeneous MNP are found within magnetotactic bacteria, a unique bacteria capable of producing magnetite nanoparticles internally under ambient conditions. Biomineralisation proteins control the properties of the MNPs, enhancing their homogeneity. One of these proteins, Mms6, has been successfully isolated and used in vitro as an additive in room-temperature co-precipitation reactions (RTCP) to produce particles of defined mono-dispersed size & morphology. When considering future industrial scale-up it is crucial to consider the costs and feasibility of an additive, as an additive that is not readily available or easily synthesized at a competitive price will not be sustainable. As such, additives selected for this research are inspired by the functional groups of biomineralisation proteins, but cost-effective, environmentally friendly, and compatible with scale-up. Diethylenetriamine (DETA), triethylenetetramine (TETA), tetraethylenepentamine (TEPA), and pentaethylenehexamine (PEHA) have been successfully used in RTCP to modulate the properties of particles synthesized, leading to the formation of octahedral nanoparticles with no use of organic solvents, heating, or toxic precursors. By extending this principle to a fluidic system, ongoing research will reveal whether the amine additives can also exert morphological control in an environment which is suited toward higher particle yield. Two fluidic systems have been employed; a peristaltic turbulent flow mixing system suitable for the rapid production of MNP, and a macrofluidic system for the synthesis of tailored nanomaterials under a laminar flow regime. The presence of the amine additives in the turbulent flow system in initial results appears to offer similar morphological control as observed under RTCP conditions, with higher proportions of octahedral particles formed. This is a proof of concept which may pave the way to green synthesis of tailored MNP on an industrial scale. Mms6 and amine additives have been used in the macrofluidic system, with Mms6 allowing magnetite to be synthesized at unfavourable ferric ratios, but no longer influencing particle size. This suggests this synthetic technique while still benefiting from the addition of additives, may not allow additives to fully influence the particles formed due to the faster timescale of reaction. The amine additives have been tested at various concentrations, the results of which will be discussed in this paper.

Keywords: bioinspired, green synthesis, fluidic, magnetite, morphological control, scale-up

Procedia PDF Downloads 97

Authors: C. Fernandez-Plaza, I. Abad, E. Diaz, I. Diaz

Abstract:

Births occurring before the 37th week of gestation are considered preterm births. A threat of preterm is defined as the beginning of regular uterine contractions, dilation and cervical effacement between 23 and 36 gestation weeks. To author's best knowledge, the factors that determine the beginning of the birth are not completely defined yet. In particular, the incidence of sleep habits on preterm births is weekly studied. The aim of this study is to develop a model to predict the factors affecting premature delivery on pregnancy, based on the above potential risk factors, including those derived from sleep habits and light exposure at night (introduced as 12 variables obtained by a telephone survey using two questionnaires previously used by other authors). Thus, three groups of variables were included in the study (maternal, fetal and sleep habits). The study was approved by Research Ethics Committee of the Principado of Asturias (Spain). An observational, retrospective and descriptive study was performed with 481 births between January 1, 2015 and May 10, 2016 in the University Central Hospital of Asturias (Spain). A statistical analysis using SPSS was carried out to compare qualitative and quantitative variables between preterm and term delivery. Chi-square test qualitative variable and t-test for quantitative variables were applied. Statistically significant differences (p < 0.05) between preterm vs. term births were found for primiparity, multi-parity, kind of conception, place of residence or premature rupture of membranes and interruption during nights. In addition to the statistical analysis, machine learning methods to look for a prediction model were tested. In particular, tree based models were applied as the trade-off between performance and interpretability is especially suitable for this study. C5.0, recursive partitioning, random forest and tree bag models were analysed using caret R-package. Cross validation with 10-folds and parameter tuning to optimize the methods were applied. In addition, different noise reduction methods were applied to the initial data using NoiseFiltersR package. The best performance was obtained by C5.0 method with Accuracy 0.91, Sensitivity 0.93, Specificity 0.89 and Precision 0.91. Some well known preterm birth factors were identified: Cervix Dilation, maternal BMI, Premature rupture of membranes or nuchal translucency analysis in the first trimester. The model also identifies other new factors related to sleep habits such as light through window, bedtime on working days, usage of electronic devices before sleeping from Mondays to Fridays or change of sleeping habits reflected in the number of hours, in the depth of sleep or in the lighting of the room. IF dilation < = 2.95 AND usage of electronic devices before sleeping from Mondays to Friday = YES and change of sleeping habits = YES, then preterm is one of the predicting rules obtained by C5.0. In this work a model for predicting preterm births is developed. It is based on machine learning together with noise reduction techniques. The method maximizing the performance is the one selected. This model shows the influence of variables related to sleep habits in preterm prediction.

Keywords: machine learning, noise reduction, preterm birth, sleep habit

Procedia PDF Downloads 113

Authors: Mary Isobelle Mullaney

Abstract:

The maxim "an unexamined life is not worth living," attributed to Socrates, prompts a contemplative reflection spanning over 32 years as a teacher educator in the Republic of Ireland. Taking time to contemplate the changes that have occurred and the current landscape provides valuable insights into the dynamic terrain of teacher preparation. The reflective journey traverses the impacts of global and societal shifts, responding to challenges, embracing advancements, and navigating the delicate balance between responsiveness to the world and the active shaping of it. The transformative events of the COVID-19 pandemic spotlighted the indispensable role of teachers in Ireland, reinforcing the critical nature of education for the well-being of pupils. Research solidifies the understanding that teachers matter and so it is worth exploring the pivotal role of the teacher educator. This reflective piece examines the changes in teacher education and explores the juxtapositions that have emerged in response to three decades of profound change. The attractiveness of teaching as a career is juxtaposed against the reality of the demands of the job, with conditions for public servants in Ireland undergoing a shift. High-level strategic discussions about increasing teacher numbers now contrast with a previous oversupply. The delicate balance between the imperative to increase enrolment (getting "bums on seats") and the gatekeeper role of teacher educators is explored, raising questions about maintaining high standards amid changing student profiles. Another poignant dichotomy involves the high demand for teachers versus the hurdles candidates face in becoming teachers. The rising cost and duration of teacher education courses raise concerns about attracting quality candidates. The perceived attractiveness of teaching as a career contends with the reality of increased demands on educators. One notable juxtaposition centres around the rapid evolution of Irish initial teacher education versus the potential risk of change overload. The Teaching Council of Ireland has spearheaded considerable changes, raising questions about the timing and evaluation of these changes. This reflection contemplates the vision of a professional teaching council versus its evolving reality and the challenges posed by the value placed on school placement in teacher preparation. The juxtapositions extend to the classroom, where theory may not seamlessly align with the lived experience. Inconsistencies between college expectations and the classroom reality prompt reflection on the effectiveness of teacher preparation programs. Addressing the changing demographic landscape of society and schools, there is a persistent incongruity between the diversity of Irish society and the profile of second-level teachers. As education undergoes a digital revolution, the enduring philosophies of education confront technological advances. This reflection highlights the tension between established practices and contemporary demands, acknowledging the irreplaceable value of face-to-face interaction while integrating technology into teacher training programs. In conclusion, this reflective journey encapsulates the intricate web of juxtapositions in Irish Initial Teacher Education. It emphasises the enduring commitment to fostering education, recognising the profound influence educators wield, and acknowledging the challenges and gratifications inherent in shaping the minds and futures of generations to come.

Keywords: Irish post primary teaching, juxtapositions, reflection, teacher education

Procedia PDF Downloads 21

Authors: Dong Yue, Hua Chen

Abstract:

The study region Xihu Harbor in Xiangshan County, Ningbo City is located in the central coast of Zhejiang Province. Concerning the wave dispating issue, Ningbo government firstly introduced Spartina alterniflora in 1980s. In the 1990s, S. alterniflora spread so rapidly thus a ‘grassland’ in the sea has been created nowadays. It has become the most important invasive plant of China’s coastal tidal flats. Although S. alterniflora had some ecological and economic functions, it has also brought series of hazards. It has ecological hazards on many aspects, including biomass and biodiversity, hydrodynamic force and sedimentation process, nutrient cycling of tidal flat, succession sequence of soil and plants and so on. On engineering, it courses problems of poor drainage and channel blocking. On economy, the hazard mainly reflected in the threat on aquaculture industry. The purpose of this study is to explore an ecological, feasible and economical way to manage Spartina alterniflora and use the land formed by it, taking Xihu Harbor in Xiangshan County as a case. Comparison method, mathematical modeling, qualitative and quantitative analysis are utilized to proceed the study. Main outcomes are as follows. By comparing a series of S. alterniflora managing methods which include the combination of mechanical cutting and hydraulic reclamation, waterlogging, herbicide and biological substitution from three standpoints – ecology, engineering and economy. It is inferred that the combination of mechanical cutting and hydraulic reclamation is among the top rank of S. alternifora managing methods. The combination of mechanical cutting and hydraulic reclamation means using large-scale mechanical equipment like large screw seagoing dredger to excavate the S. alterniflora with root and mud together. Then the mix of mud and grass was blown off nearby coastal tidal zone transported by pipelines, which can cushion the silt of tidal zone to form a land. However, as man-made land by coast, the reclamation area’s ecological sensitivity is quite high and will face high possibility of flood threat. Therefore, the reclamation area has many reasonability requirements, including ones on location, specific scope, water surface rate, direction of main watercourse, site of water-gate, the ratio of ecological land to urban construction land. These requirements all became important basis when the planning was being made. The water system planning, green space system planning, road structure and land use all need to accommodate the ecological requests. Besides, the profits from the formed land is the managing project’s source of funding, so how to utilize land efficiently is another considered point in the planning. It is concluded that by aiming at managing a large area of S. alterniflora, the combination of mechanical cutting and hydraulic reclamation is an ecological, feasible and economical method. The planning of reclamation area should fully respect the natural environment and possible disasters. Then the planning which makes land use efficient, reasonable, ecological will promote the development of the area’s city construction.

Keywords: ecological management, ecological planning method, reclamation area, Spartina alternifora, Xihu harbor

Procedia PDF Downloads 287