Search results for: Heyd–Scuseria–Ernzerhof screened hybrid functional
Commenced in January 2007
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Paper Count: 4874

Search results for: Heyd–Scuseria–Ernzerhof screened hybrid functional

284 Company-Independent Standardization of Timber Construction to Promote Urban Redensification of Housing Stock

Authors: Andreas Schweiger, Matthias Gnigler, Elisabeth Wieder, Michael Grobbauer

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Especially in the alpine region, available areas for new residential development are limited. One possible solution is to exploit the potential of existing settlements. Urban redensification, especially the addition of floors to existing buildings, requires efficient, lightweight constructions with short construction times. This topic is being addressed in the five-year Alpine Building Centre. The focus of this cooperation between Salzburg University of Applied Sciences and RSA GH Studio iSPACE is on transdisciplinary research in the fields of building and energy technology, building envelopes and geoinformation, as well as the transfer of research results to industry. One development objective is a system of wood panel system construction with a high degree of prefabrication to optimize the construction quality, the construction time and the applicability for small and medium-sized enterprises. The system serves as a reliable working basis for mastering the complex building task of redensification. The technical solution is the development of an open system in timber frame and solid wood construction, which is suitable for a maximum two-story addition of residential buildings. The applicability of the system is mainly influenced by the existing building stock. Therefore, timber frame and solid timber construction are combined where necessary to bridge large spans of the existing structure while keeping the dead weight as low as possible. Escape routes are usually constructed in reinforced concrete and are located outside the system boundary. Thus, within the framework of the legal and normative requirements of timber construction, a hybrid construction method for redensification created. Component structure, load-bearing structure and detail constructions are developed in accordance with the relevant requirements. The results are directly applicable in individual cases, with the exception of the required verifications. In order to verify the practical suitability of the developed system, stakeholder workshops are held on the one hand, and the system is applied in the planning of a two-storey extension on the other hand. A company-independent construction standard offers the possibility of cooperation and bundling of capacities in order to be able to handle larger construction volumes in collaboration with several companies. Numerous further developments can take place on the basis of the system, which is under open license. The construction system will support planners and contractors from design to execution. In this context, open means publicly published and freely usable and modifiable for own use as long as the authorship and deviations are mentioned. The companies are provided with a system manual, which contains the system description and an application manual. This manual will facilitate the selection of the correct component cross-sections for the specific construction projects by means of all component and detail specifications. This presentation highlights the initial situation, the motivation, the approach, but especially the technical solution as well as the possibilities for the application. After an explanation of the objectives and working methods, the component and detail specifications are presented as work results and their application.

Keywords: redensification, SME, urban development, wood building system

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283 Rheological Properties of Thermoresponsive Poly(N-Vinylcaprolactam)-g-Collagen Hydrogel

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

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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

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282 Design, Fabrication and Analysis of Molded and Direct 3D-Printed Soft Pneumatic Actuators

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

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

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

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281 Stable Time Reversed Integration of the Navier-Stokes Equation Using an Adjoint Gradient Method

Authors: Jurriaan Gillissen

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This work is concerned with stabilizing the numerical integration of the Navier-Stokes equation (NSE), backwards in time. Applications involve the detection of sources of, e.g., sound, heat, and pollutants. Stable reverse numerical integration of parabolic differential equations is also relevant for image de-blurring. While the literature addresses the reverse integration problem of the advection-diffusion equation, the problem of numerical reverse integration of the NSE has, to our knowledge, not yet been addressed. Owing to the presence of viscosity, the NSE is irreversible, i.e., when going backwards in time, the fluid behaves, as if it had a negative viscosity. As an effect, perturbations from the perfect solution, due to round off errors or discretization errors, grow exponentially in time, and reverse integration of the NSE is inherently unstable, regardless of using an implicit time integration scheme. Consequently, some sort of filtering is required, in order to achieve a stable, numerical, reversed integration. The challenge is to find a filter with a minimal adverse affect on the accuracy of the reversed integration. In the present work, we explore an adjoint gradient method (AGM) to achieve this goal, and we apply this technique to two-dimensional (2D), decaying turbulence. The AGM solves for the initial velocity field u0 at t = 0, that, when integrated forward in time, produces a final velocity field u1 at t = 1, that is as close as is feasibly possible to some specified target field v1. The initial field u0 defines a minimum of a cost-functional J, that measures the distance between u1 and v1. In the minimization procedure, the u0 is updated iteratively along the gradient of J w.r.t. u0, where the gradient is obtained by transporting J backwards in time from t = 1 to t = 0, using the adjoint NSE. The AGM thus effectively replaces the backward integration by multiple forward and backward adjoint integrations. Since the viscosity is negative in the adjoint NSE, each step of the AGM is numerically stable. Nevertheless, when applied to turbulence, the AGM develops instabilities, which limit the backward integration to small times. This is due to the exponential divergence of phase space trajectories in turbulent flow, which produces a multitude of local minima in J, when the integration time is large. As an effect, the AGM may select unphysical, noisy initial conditions. In order to improve this situation, we propose two remedies. First, we replace the integration by a sequence of smaller integrations, i.e., we divide the integration time into segments, where in each segment the target field v1 is taken as the initial field u0 from the previous segment. Second, we add an additional term (regularizer) to J, which is proportional to a high-order Laplacian of u0, and which dampens the gradients of u0. We show that suitable values for the segment size and for the regularizer, allow a stable reverse integration of 2D decaying turbulence, with accurate results for more then O(10) turbulent, integral time scales.

Keywords: time reversed integration, parabolic differential equations, adjoint gradient method, two dimensional turbulence

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280 Approach on Conceptual Design and Dimensional Synthesis of the Linear Delta Robot for Additive Manufacturing

Authors: Efrain Rodriguez, Cristhian Riano, Alberto Alvares

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In recent years, robots manipulators with parallel architectures are used in additive manufacturing processes – 3D printing. These robots have advantages such as speed and lightness that make them suitable to help with the efficiency and productivity of these processes. Consequently, the interest for the development of parallel robots for additive manufacturing applications has increased. This article deals with the conceptual design and dimensional synthesis of the linear delta robot for additive manufacturing. Firstly, a methodology based on structured processes for the development of products through the phases of informational design, conceptual design and detailed design is adopted: a) In the informational design phase the Mudge diagram and the QFD matrix are used to aid a set of technical requirements, to define the form, functions and features of the robot. b) In the conceptual design phase, the functional modeling of the system through of an IDEF0 diagram is performed, and the solution principles for the requirements are formulated using a morphological matrix. This phase includes the description of the mechanical, electro-electronic and computational subsystems that constitute the general architecture of the robot. c) In the detailed design phase, a digital model of the robot is drawn on CAD software. A list of commercial and manufactured parts is detailed. Tolerances and adjustments are defined for some parts of the robot structure. The necessary manufacturing processes and tools are also listed, including: milling, turning and 3D printing. Secondly, a dimensional synthesis method applied on design of the linear delta robot is presented. One of the most important key factors in the design of a parallel robot is the useful workspace, which strongly depends on the joint space, the dimensions of the mechanism bodies and the possible interferences between these bodies. The objective function is based on the verification of the kinematic model for a prescribed cylindrical workspace, considering geometric constraints that possibly lead to singularities of the mechanism. The aim is to determine the minimum dimensional parameters of the mechanism bodies for the proposed workspace. A method based on genetic algorithms was used to solve this problem. The method uses a cloud of points with the cylindrical shape of the workspace and checks the kinematic model for each of the points within the cloud. The evolution of the population (point cloud) provides the optimal parameters for the design of the delta robot. The development process of the linear delta robot with optimal dimensions for additive manufacture is presented. The dimensional synthesis enabled to design the mechanism of the delta robot in function of the prescribed workspace. Finally, the implementation of the robotic platform developed based on a linear delta robot in an additive manufacturing application using the Fused Deposition Modeling (FDM) technique is presented.

Keywords: additive manufacturing, delta parallel robot, dimensional synthesis, genetic algorithms

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279 Magneto-Luminescent Biocompatible Complexes Based on Alloyed Quantum Dots and Superparamagnetic Iron Oxide Nanoparticles

Authors: A. Matiushkina, A. Bazhenova, I. Litvinov, E. Kornilova, A. Dubavik, A. Orlova

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Magnetic-luminescent complexes based on superparamagnetic iron oxide nanoparticles (SPIONs) and semiconductor quantum dots (QDs) have been recognized as a new class of materials that have high potential in modern medicine. These materials can serve for theranostics of oncological diseases, and also as a target agent for drug delivery. They combine the qualities characteristic of magnetic nanoparticles, that is, magneto-controllability and the ability to local heating under the influence of an external magnetic field, as well as phosphors, due to luminescence of which, for example, early tumor imaging is possible. The complexity of creating complexes is the energy transfer between particles, which quenches the luminescence of QDs in complexes with SPIONs. In this regard, a relatively new type of alloyed (CdₓZn₁₋ₓSeᵧS₁₋ᵧ)-ZnS QDs is used in our work. The presence of a sufficiently thick gradient semiconductor shell in alloyed QDs makes it possible to reduce the probability of energy transfer from QDs to SPIONs in complexes. At the same time, Forster Resonance Energy Transfer (FRET) is a perfect instrument to confirm the formation of complexes based on QDs and different-type energy acceptors. The formation of complexes in the aprotic bipolar solvent dimethyl sulfoxide is ensured by the coordination of the carboxyl group of the stabilizing QD molecule (L-cysteine) on the surface iron atoms of the SPIONs. An analysis of the photoluminescence (PL) spectra has shown that a sequential increase in the SPIONs concentration in the samples is accompanied by effective quenching of the luminescence of QDs. However, it has not confirmed the formation of complexes yet, because of a decrease in the PL intensity of QDs due to reabsorption of light by SPIONs. Therefore, a study of the PL kinetics of QDs at different SPIONs concentrations was made, which demonstrates that an increase in the SPIONs concentration is accompanied by a symbatic reduction in all characteristic PL decay times. It confirms the FRET from QDs to SPIONs, which indicates the QDs/SPIONs complex formation, rather than a spontaneous aggregation of QDs, which is usually accompanied by a sharp increase in the percentage of the QD fraction with the shortest characteristic PL decay time. The complexes have been studied by the magnetic circular dichroism (MCD) spectroscopy that allows one to estimate the response of magnetic material to the applied magnetic field and also can be useful to check SPIONs aggregation. An analysis of the MCD spectra has shown that the complexes have zero residual magnetization, which is an important factor for using in biomedical applications, and don't contain SPIONs aggregates. Cell penetration, biocompatibility, and stability of QDs/SPIONs complexes in cancer cells have been studied using HeLa cell line. We have found that the complexes penetrate in HeLa cell and don't demonstrate cytotoxic effect up to 25 nM concentration. Our results clearly demonstrate that alloyed (CdₓZn₁₋ₓSeᵧS₁₋ᵧ)-ZnS QDs can be successfully used in complexes with SPIONs reached new hybrid nanostructures, which combine bright luminescence for tumor imaging and magnetic properties for targeted drug delivery and magnetic hyperthermia of tumors. Acknowledgements: This work was supported by the Ministry of Science and Higher Education of Russian Federation, goszadanie no. 2019-1080 and was financially supported by Government of Russian Federation, Grant 08-08.

Keywords: alloyed quantum dots, magnetic circular dichroism, magneto-luminescent complexes, superparamagnetic iron oxide nanoparticles

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278 The Use of Rotigotine to Improve Hemispatial Neglect in Stroke Patients at the Charing Cross Neurorehabilitation Unit

Authors: Malab Sana Balouch, Meenakshi Nayar

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Hemispatial Neglect is a common disorder primarily associated with right hemispheric stroke, in the acute phase of which it can occur up to 82% of the time. Such individuals fail to acknowledge or respond to people and objects in their left field of vision due to deficits in attention and awareness. Persistent hemispatial neglect significantly impedes post-stroke recovery, leading to longer hospital stays post-stroke, increased functional dependency, longer-term disability in ADLs and increased risk of falls. Recently, evidence has emerged for the use of dopamine agonist Rotigotine in neglect. The aim of our Quality Improvement Project (QIP) is to evaluate and better the current protocols and practice in assessment, documentation and management of neglect and rotigotine use at the Neurorehabilitation unit at Charing Cross Hospital (CNRU). In addition, it brings light to rotigotine use in the management of hemispatial neglect and paves the way for future research in the field. Our QIP was based in the CNRU. All patients admitted to the CNRU suffering from a right-sided stroke from 2nd of February 2018 to the 2nd of February 2021 were included in the project. Each patient’s multidisciplinary team report and hospital notes were searched for information, including bio-data, fulfilment of the inclusion criteria (having hemispatial neglect) and data related to rotigotine use. This includes whether or not the drug was administered, any contraindications to drug in patients that did not receive it, and any therapeutic benefits(subjective or objective improvement in neglect) in those that did receive the rotigotine. Data was simultaneously entered into excel sheet and further statistical analysis was done on SPSS 20.0. Out of 80 patients suffering from right sided strokes, 72.5% were infarcts and 27.5% were hemorrhagic strokes, with vast majority of both types of strokes were in the middle cerebral artery territory (MCA). A total of 31 (38.8%) of our patients were noted to have hemispatial neglect, with the highest number of cases being associated with MCA strokes. Almost half of our patients with MCA strokes suffered from neglect. Neglect was more common in male patients. Out of the 31 patients suffering from visuospatial neglect, only 16% actually received rotigotine and 80% of them were noted to have an objective improvement in their neglect tests and 20% revealed subjective improvement. After thoroughly going through neglect-associated documentation, the following recommendations/plans were put in place for the future. We plan to liaise with the occupational therapy team at our rehab unit to set a battery of tests that would be done on all patients presenting with neglect and recommend clear documentation of outcomes of each neglect screen under it. Also to create two proformas; one for the therapy team to aid in systematic documentation of neglect screens done prior to and after rotigotine administration and a second proforma for the medical team with clear documentation of rotigotine use, its benefits and any contraindications if not administered.

Keywords: hemispatial Neglect, right hemispheric stroke, rotigotine, neglect, dopamine agonist

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277 Outcome of Naive SGLT2 Inhibitors Among ICU Admitted Acute Stroke with T2DM Patients a Prospective Cohort Study in NCMultispecialty Hospital, Biratnagar, Nepal

Authors: Birendra Kumar Bista, Rhitik Bista, Prafulla Koirala, Lokendra Mandal, Nikrsh Raj Shrestha, Vivek Kattel

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Introduction: Poorly controlled diabetes is associated with cause and poor outcome of stroke. High blood sugar reduces cerebral blood flow, increases intracranial pressure, cerebral edema and neuronal death, especially among patients with poorly controlled diabetes.1 SGLT2 inhibitors are associated with 50% reduction in hemorrhagic stroke compared with placebo. SGLT2 inhibitors decrease cardiovascular events via reducing glucose, blood pressure, weight, arteriosclerosis, albuminuria and reduction of atrial fibrillation.2,3 No study has been documented in low income countries to see the role of post stroke SGLT2 inhibitors on diabetic patients at and after ICU admission. Aims: The aim of the study was to measure the 12 months outcome of diabetic patients with acute stroke admitted in ICU set up with naïve SGLT2 inhibitors add on therapy. Method: It was prospective cohort study carried out in a 250 bedded tertiary neurology care hospital at the province capital Biratnagar Nepal. Diabetic patient with acute stroke admitted in ICU from 1st January 2022 to 31st December 2022 who were not under SGLT2 inhibitors were included in the study. These patients were managed as per hospital protocol. Empagliflozin was added to the alternate enrolled patients. Empagliflozin was continued at the time of discharged and during follow up unless contraindicated. These patients were followed up for 12 months. Outcome measured were mortality, morbidity requiring readmission or hospital visit other than regular follow up, SGLT2 inhibitors related adverse events, neuropsychiatry comorbidity, functional status and biochemical parameters. Ethical permission was taken from hospital administration and ethical board. Results: Among 147 diabetic cases 68 were not treated with empagliflozin whereas 67 cases were started the SGLT2 inhibitors. HbA1c level and one year mortality was significantly low among patients on empaglifozin arm. Over a period of 12 months 427 acute stroke patients were admitted in the ICU. Out of them 44% were female, 61% hypertensive, 34% diabetic, 57% dyslipidemia, 26% smoker and with median age of 45 years. Among 427 cases 4% required neurosurgical interventions and 76% had hemorrhagic CVA. The most common reason for ICU admission was GCS<8 (51%). The median ICU stay was 5 days. ICU mortality was 21% whereas 1 year mortality was 41% with most common reason being pneumonia. Empaglifozin related adverse effect was seen in 11% most commonly lower urinary tract infection in 6%. Conclusion: Empagliflozin can safely be started among acute stroke with better Hba1C control and low mortality outcome compared to treatment without SGLT2 inhibitor.

Keywords: diabetes, ICU, mortality, SGLT2 inhibitors, stroke

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276 Synergistic Effect of Chondroinductive Growth Factors and Synovium-Derived Mesenchymal Stem Cells on Regeneration of Cartilage Defects in Rabbits

Authors: M. Karzhauov, А. Mukhambetova, M. Sarsenova, E. Raimagambetov, V. Ogay

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Regeneration of injured articular cartilage remains one of the most difficult and unsolved problems in traumatology and orthopedics. Currently, for the treatment of cartilage defects surgical techniques for stimulation of the regeneration of cartilage in damaged joints such as multiple microperforation, mosaic chondroplasty, abrasion and microfractures is used. However, as shown by clinical practice, they can not provide a full and sustainable recovery of articular hyaline cartilage. In this regard, the current high hopes in the regeneration of cartilage defects reasonably are associated with the use of tissue engineering approaches to restore the structural and functional characteristics of damaged joints using stem cells, growth factors and biopolymers or scaffolds. The purpose of the present study was to investigate the effects of chondroinductive growth factors and synovium-derived mesenchymal stem cells (SD-MSCs) on the regeneration of cartilage defects in rabbits. SD-MSCs were isolated from the synovium membrane of Flemish giant rabbits, and expanded in complete culture medium α-MEM. Rabbit SD-MSCs were characterized by CFU-assay and by their ability to differentiate into osteoblasts, chondrocytes and adipocytes. The effects of growth factors (TGF-β1, BMP-2, BMP-4 and IGF-I) on MSC chondrogenesis were examined in micromass pellet cultures using histological and biochemical analysis. Articular cartilage defect (4mm in diameter) in the intercondylar groove of the patellofemoral joint was performed with a kit for the mosaic chondroplasty. The defect was made until subchondral bone plate. Delivery of SD-MSCs and growth factors was conducted in combination with hyaloronic acid (HA). SD-MSCs, growth factors and control groups were compared macroscopically and histologically at 10, 30, 60 and 90 days aftrer intra-articular injection. Our in vitro comparative study revealed that TGF-β1 and BMP-4 are key chondroinductive factors for both the growth and chondrogenesis of SD-MSCs. The highest effect on MSC chondrogenesis was observed with the synergistic interaction of TGF-β1 and BMP-4. In addition, biochemical analysis of the chondrogenic micromass pellets also revealed that the levels of glycosaminoglycans and DNA after combined treatment with TGF-β1 and BMP-4 was significantly higher in comparison to individual application of these factors. In vivo study showed that for complete regeneration of cartilage defects with intra-articular injection of SD-MSCs with HA takes time 90 days. However, single injection of SD-MSCs in combiantion with TGF-β1, BMP-4 and HA significantly promoted regeneration rate of the cartilage defects in rabbits. In this case, complete regeneration of cartilage defects was observed in 30 days after intra-articular injection. Thus, our in vitro and in vivo study demonstrated that combined application of rabbit SD-MSC with chondroinductive growth factors and HA results in strong synergistic effect on the chondrogenesis significantly enhancing regeneration of the damaged cartilage.

Keywords: Mesenchymal stem cells, synovium, chondroinductive factors, TGF-β1, BMP-2, BMP-4, IGF-I

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275 To Smile or Not to Smile: How Engendered Facial Cues affect Hiring Decisions

Authors: Sabrina S. W. Chan, Emily Schwartzman, Nicholas O. Rule

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Past literature showed mixed findings on how smiling affects a person’s chance of getting hired. On one hand, smiling suggests enthusiasm, cooperativeness, and enthusiasm, which can elicit positive impressions. On the other hand, smiling can suggest weaker professionalism or a filler to hide nervousness, which can lower a candidate’s perceived competence. Emotion expressions can also be perceived differently depending on the person’s gender and can activate certain gender stereotypes. Women especially face a double bind with respect to hiring decisions and smiling. Because women are socially expected to smile more, those who do not smile will be considered stereotype incongruent. This becomes a noisy signal to employers and may lower their chance of being hired. However, women’s smiling as a formality may also be an obstacle. They are more likely to put on fake smiles; but if they do, they are also likely to be perceived as inauthentic and over-expressive. This paper sought to investigate how smiling affects hiring decisions, and whether this relationship is moderated by gender. In Study 1, participants were shown a series of smiling and emotionally neutral face images, incorporated into fabricated LinkedIn profiles. Participants were asked to rate how hireable they thought that candidate was. Results showed that participants rated smiling candidates as more hireable than nonsmiling candidates, and that there was no difference in gender. Moreover, individuals who did not study business were more biased in their perceptions than those who did. Since results showed a trending favoritism over female targets, in suspect of desirability bias, a second study was conducted to collect implicit measures behind the decision-making process. In Study 2, a mouse-tracking design was adopted to explore whether participants’ implicit attitudes were different from their explicit responses on hiring. Participants asked to respond whether they would offer an interview to a candidate. Findings from Study 1 was replicated in that smiling candidates received more offers than neutral-faced candidates. Results also showed that female candidates received significantly more offers than male candidates but was associated with higher attractiveness ratings. There were no significant findings in reaction time or change of decisions. However, stronger hesitation was detected for responses made towards neutral targets when participants perceived the given position as masculine, implying a conscious attempt of making situational judgments (e.g., considering candidate’s personality and job fit) to override automatic processing (evaluations based on attractiveness). Future studies would look at how these findings differ for positions which are stereotypically masculine (e.g., surgeons) and stereotypically feminine (e.g., kindergarten teachers). Current findings have strong implications for developing bias-free hiring policies in workplace, especially for organizations who maintain online/hybrid working arrangements in the post-pandemic era. This also bridges the literature gap between face perception and gender discrimination, highlighting how engendered facial cues can affect individual’s career development and organization’s success in diversity and inclusion.

Keywords: engendered facial cues, face perception, gender stereotypes, hiring decisions, smiling, workplace discrimination

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274 Attention and Memory in the Music Learning Process in Individuals with Visual Impairments

Authors: Lana Burmistrova

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Introduction: The influence of visual impairments on several cognitive processes used in the music learning process is an increasingly important area in special education and cognitive musicology. Many children have several visual impairments due to the refractive errors and irreversible inhibitors. However, based on the compensatory neuroplasticity and functional reorganization, congenitally blind (CB) and early blind (EB) individuals use several areas of the occipital lobe to perceive and process auditory and tactile information. CB individuals have greater memory capacity, memory reliability, and less false memory mechanisms are used while executing several tasks, they have better working memory (WM) and short-term memory (STM). Blind individuals use several strategies while executing tactile and working memory n-back tasks: verbalization strategy (mental recall), tactile strategy (tactile recall) and combined strategies. Methods and design: The aim of the pilot study was to substantiate similar tendencies while executing attention, memory and combined auditory tasks in blind and sighted individuals constructed for this study, and to investigate attention, memory and combined mechanisms used in the music learning process. For this study eight (n=8) blind and eight (n=8) sighted individuals aged 13-20 were chosen. All respondents had more than five years music performance and music learning experience. In the attention task, all respondents had to identify pitch changes in tonal and randomized melodic pairs. The memory task was based on the mismatch negativity (MMN) proportion theory: 80 percent standard (not changed) and 20 percent deviant (changed) stimuli (sequences). Every sequence was named (na-na, ra-ra, za-za) and several items (pencil, spoon, tealight) were assigned for each sequence. Respondents had to recall the sequences, to associate them with the item and to detect possible changes. While executing the combined task, all respondents had to focus attention on the pitch changes and had to detect and describe these during the recall. Results and conclusion: The results support specific features in CB and EB, and similarities between late blind (LB) and sighted individuals. While executing attention and memory tasks, it was possible to observe the tendency in CB and EB by using more precise execution tactics and usage of more advanced periodic memory, while focusing on auditory and tactile stimuli. While executing memory and combined tasks, CB and EB individuals used passive working memory to recall standard sequences, active working memory to recall deviant sequences and combined strategies. Based on the observation results, assessment of blind respondents and recording specifics, following attention and memory correlations were identified: reflective attention and STM, reflective attention and periodic memory, auditory attention and WM, tactile attention and WM, auditory tactile attention and STM. The results and the summary of findings highlight the attention and memory features used in the music learning process in the context of blindness, and the tendency of the several attention and memory types correlated based on the task, strategy and individual features.

Keywords: attention, blindness, memory, music learning, strategy

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273 Enhanced Anti-Inflammatory and Antioxidant Activities of Perna canaliculus Oil Extract and Low Molecular Weight Fucoidan from Undaria pinnatifida

Authors: Belgheis Ebrahimi, Jun Lu

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In recent years, there has been a growing recognition of the potential of marine-based functional foods and combination therapies in promoting a healthy lifestyle and exploring their effectiveness in preventing or treating diseases. The combination of marine bioactive compounds or extracts offers synergistic or enhancement effects through various mechanisms, including multi-target actions, improved bioavailability, enhanced bioactivity, and mitigation of potential adverse effects. Both the green-lipped mussel (GLM) and fucoidan derived from brown seaweed are rich in bioactivities. These two, mussel and fucoidan, have not been previously formulated together. This study aims to combine GLM oil from Perna canaliculus with low molecular weight fucoidan (LMWF) extracted from Undaria pinnatifida to investigate the unique mixture’s anti-inflammatory and antioxidant properties. The cytotoxicity of individual compounds and combinations was assessed using the MTT assay in (THP-1 and RAW264.7) cell lines. The anti-inflammatory activity of mussel-fucoidan was evaluated by treating LPS-stimulated human monocyte and macrophage (THP1-1) cells. Subsequently, the inflammatory cytokines released into the supernatant of these cell lines were quantified via ELISA. Antioxidant activity was determined by using the free radical scavenging assay (DPPH). DPPH assay demonstrated that the radical scavenging activity of the combinations, particularly at concentrations exceeding 1 mg/ml, showed a significantly higher percentage of inhibition when compared to the individual component. This suggests an enhancement effect when the two compounds are combined, leading to increased antioxidant activity. In terms of immunomodulatory activity, the individual compounds exhibited distinct behaviors. GLM oil displayed a higher ability to suppress the cytokine TNF- compared to LMWF. Interestingly, the LMWF fraction, when used individually, did not demonstrate TNF- suppression. However, when combined with GLM, the TNF- suppression (anti-inflammatory) activity of the combination was better than GLM or LWMF alone. This observation underscores the potential for enhancement interactions between the two components in terms of anti-inflammatory properties. This study revealed that each individual compound, LMWF, and GLM, possesses unique and notable bioactivity. The combination of these two individual compounds results in an enhancement effect, where the bioactivity of each is enhanced, creating a superior combination. This suggests that the combination of LMWF and GLM has the potential to offer a more potent and multifaceted therapeutic effect, particularly in the context of antioxidant and anti-inflammatory activities. These findings hold promise for the development of novel therapeutic interventions or supplements that harness the enhancement effects.

Keywords: combination, enhancement effect, perna canaliculus, undaria pinnatifida

Procedia PDF Downloads 63
272 Improving Preconception Health and Lifestyle Behaviours through Digital Health Intervention: The OptimalMe Program

Authors: Bonnie R. Brammall, Rhonda M. Garad, Helena J. Teede, Cheryce L. Harrison

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Introduction: Reproductive aged women are at high-risk for accelerated weight gain and obesity development, with pregnancy recognised as a critical contributory life phase. Healthy lifestyle interventions during the preconception and antenatal period improve maternal and infant health outcomes. Yet, interventions from preconception through to postpartum and translation and implementation into real-world healthcare settings remain limited. OptimalMe is a randomised, hybrid implementation effectiveness study of evidence-based healthy lifestyle intervention. Here, we report engagement, acceptability of the intervention during preconception, and self-reported behaviour change outcomes as a result of the preconception phase of the intervention. Methods: Reproductive aged women who upgraded their private health insurance to include pregnancy and birth cover, signalling a pregnancy intention, were invited to participate. Women received access to an online portal with preconception health and lifestyle modules, goal-setting and behaviour change tools, monthly SMS messages, and two coaching sessions (randomised to video or phone) prior to pregnancy. Results: Overall n=527 expressed interest in participating. Of these, n=33 did not meet inclusion criteria, n=8 were not contactable for eligibility screening, and n=177 failed to engage after the screening, leaving n=309 who were enrolled in OptimalMe and randomised to intervention delivery method. Engagement with coaching sessions dropped by 25% for session two, with no difference between intervention groups. Women had a mean (SD) age of 31.7 (4.3) years and, at baseline, a self-reported mean BMI of 25.7 (6.1) kg/m², with 55.8% (n=172) of a healthy BMI. Behaviour was sub-optimal with infrequent self-weighing (38.1%), alcohol consumption prevalent (57.1%), sub-optimal pre-pregnancy supplementation (61.5%), and incomplete medical screening. Post-intervention 73.2% of women reported engagement with a GP for preconception care and improved lifestyle behaviour (85.5%), since starting OptimalMe. Direct pre-and-post comparison of individual participant data showed that of 322 points of potential change (up-to-date cervical screening, elimination of high-risk behaviours [alcohol, drugs, smoking], uptake of preconception supplements and improved weighing habits) 158 (49.1%) points of change were achieved. Health coaching sessions were found to improve accountability and confidence, yet further personalisation and support were desired. Engagement with video and phone sessions was comparable, having similar impacts on behaviour change, and both methods were well accepted and increased women's accountability. Conclusion: A low-intensity digital health and lifestyle program with embedded health coaching can improve the uptake of preconception care and lead to self-reported behaviour change. This is the first program of its kind to reach an otherwise healthy population of women planning a pregnancy. Women who were otherwise healthy showed divergence from preconception health and lifestyle objectives and benefited from the intervention. OptimalMe shows promising results for population-based behaviour change interventions that can improve preconception lifestyle habits and increase engagement with clinical health care for pregnancy preparation.

Keywords: preconception, pregnancy, preventative health, weight gain prevention, self-management, behaviour change, digital health, telehealth, intervention, women's health

Procedia PDF Downloads 78
271 The Impact of Encapsulated Raspberry Juice on the Surface Colour of Enriched White Chocolate

Authors: Ivana Loncarevic, Biljana Pajin, Jovana Petrovic, Aleksandar Fistes, Vesna Tumbas Saponjac, Danica Zaric

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Chocolate is a complex rheological system usually defined as a suspension consisting of non-fat particles dispersed in cocoa butter as a continuous fat phase. Dark chocolate possesses polyphenols as major constituents whose dietary consumption has been associated with beneficial effects. Milk chocolate is formulated with a lower percentage of cocoa bean liquor than dark chocolate and it often contains lower amounts of polyphenols, while in white chocolate the fat-free cocoa solids are left out completely. Following the current trend of development of functional foods, there is an idea to create enriched white chocolate with the addition of encapsulated bioactive compounds from berry fruits. The aim of this study was to examine the surface colour of enriched white chocolate with the addition of 6, 8, and 10% of raspberry juice encapsulated in maltodextrins, in order to preserve the stability, bioactivity, and bioavailability of the active ingredients. The surface color of samples was measured by MINOLTA Chroma Meter CR-400 (Minolta Co., Ltd., Osaka, Japan) using D 65 lighting, a 2º standard observer angle and an 8-mm aperture in the measuring head. The following CIELab color coordinates were determined: L* – lightness, a* – redness to greenness and b* – yellowness to blueness. The addition of raspberry encapsulates led to the creation of new type of enriched chocolate. Raspberry encapsulate changed the values of the lightness (L*), a* (red tone) and b* (yellow tone) measured on the surface of enriched chocolate in accordance with applied concentrations. White chocolate has significantly (p < 0.05) highest L* (74.6) and b* (20.31) values of all samples indicating the bright surface of the white chocolate, as well as a high share of a yellow tone. At the same time, white chocolate has the negative a* value (-1.00) on its surface which includes green tones. Raspberry juice encapsulate has the darkest surface with significantly (p < 0.05) lowest value of L* (42.75), where increasing of its concentration in enriched chocolates decreases their L* values. Chocolate with 6% of encapsulate has significantly (p < 0.05) highest value of L* (60.56) in relation to enriched chocolate with 8% of encapsulate (53.57), and 10% of encapsulate (51.01). a* value measured on the surface of white chocolate is negative (-1.00) tending towards green tones. Raspberry juice encapsulates increases red tone in enriched chocolates in accordance with the added amounts (23.22, 30.85, and 33.32 in enriched chocolates with 6, 8, and 10% encapsulated raspberry juice, respectively). The presence of yellow tones in enriched chocolates significantly (p < 0.05) decreases with the addition of E (with b* value 5.21), from 10.01 in enriched chocolate with a minimal amount of raspberry juice encapsulates to 8.91 in chocolate with a maximum concentration of raspberry juice encapsulate. The addition of encapsulated raspberry juice to white chocolate led to the creation of new type of enriched chocolate with attractive color. The research in this paper was conducted within the project titled ‘Development of innovative chocolate products fortified with bioactive compounds’ (Innovation Fund Project ID 50051).

Keywords: color, encapsulated raspberry juice, polyphenols, white chocolate

Procedia PDF Downloads 160
270 Removal of Heavy Metal Ions from Aqueous Solution by Polymer Enhanced Ultrafiltration Using Unmodified Starch as Biopolymer

Authors: Nurul Huda Baharuddin, Nik Meriam Nik Sulaiman, Mohammed Kheireddine Aroua

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The effects of pH, polymer concentration, and metal ions feed concentration for four selected heavy metals Zn (II), Pb (II), Cr (III) and Cr (VI) were tested by using Polymer Enhanced Ultrafiltration (PEUF). An alternative biopolymer namely unmodified starch is proposed as a binding reagent in consequences, as compared to commonly used water-soluble polymers namely polyethylene glycol (PEG) and polyethyleneimine (PEI) in the removal of selected four heavy metal ions. The speciation species profiles of four selected complexes ions namely Zn (II), Pb (II), Cr (III) and Cr (VI) and the present of hydroxides ions (OH-) in variously charged ions were investigated by available software at certain pH range. In corresponds to identify the potential of complexation behavior between metal ion-polymers, potentiometric titration studies were obtained at first before carried out experimental works. Experimental works were done using ultrafiltration systems obtained by laboratory ultrafiltration bench scale equipped with 10 kDa polysulfone hollow fiber membrane. Throughout the laboratory works, the rejection coefficient and permeate flux were found to be significantly affected by the main operating parameter, namely the effects of pH, polymer composition and metal ions concentrations. The interaction of complexation between two binding polymers namely unmodified starch and PEG were occurred due to physical attraction of metal ions to the polymer on the molecular surface with high possibility of chemical occurrence. However, these selected metal ions are mainly complexes by polymer functional groups whenever there is interaction with PEI polymer. For study of single metal ions solutions, Zn (II) ions' rejections approaching over 90% were obtained at pH 7 for each tested polymer. This behavior was similar to Pb (II), Cr (III) and Cr (VI); where the rejections were obtained at lower acidic pH and increased at neutral pH of 7. Different behavior was found by Cr (VI) ions where a high rejection was only achieved at acidic pH region with PEI. Polymer concentration and metal ions concentration are found to have a significant effect on rejections. For mixed metal ion solutions, the behavior of metal ion rejections was similar to single metal ion solutions for investigation on the effects of pH. Rejection values were high at pH 7 for Zn (II) pH 7 for Zn (II) and Cr (III) ions, corresponding to higher rejections with unmodified starch. Pb (II) ions obtained high rejections when tested with PEG whenever carried out in mixed metal ion solutions. High Cr (VI) ions' rejection was found with PEI in single and mixed metal ions solutions at neutral pH range. The influence of starch’s granule structure towards the rejections of these four selected metal ions is found to be attracted in a non-ionic manner. No significant effects on permeate flux were obtained when tested at different pH ranges, polymer concentrations and metal ions feed either by single or mixtures metal ions solutions. Canizares Model was employed as the theoretical model to predict permeate flux and metal ions retention on the study of heavy metal ions removal.

Keywords: polyethyleneimine, polyethylene glycol, polymer-enhanced ultrafiltration, unmodified starch

Procedia PDF Downloads 148
269 Satellite Connectivity for Sustainable Mobility

Authors: Roberta Mugellesi Dow

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

Keywords: sustainability, connectivity, mobility, satellites

Procedia PDF Downloads 110
268 Comparing the Knee Kinetics and Kinematics during Non-Steady Movements in Recovered Anterior Cruciate Ligament Injured Badminton Players against an Uninjured Cohort: Case-Control Study

Authors: Anuj Pathare, Aleksandra Birn-Jeffery

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Background: The Anterior Cruciate Ligament(ACL) helps stabilize the knee joint minimizing tibial anterior translation. Anterior Cruciate Ligament (ACL) injury is common in racquet sports and often occurs due to sudden acceleration, deceleration or changes of direction. This mechanism in badminton most commonly occurs during landing after an overhead stroke. Knee biomechanics during dynamic movements such as walking, running and stair negotiation, do not return to normal for more than a year after an ACL reconstruction. This change in the biomechanics may lead to re-injury whilst performing non-steady movements during sports, where these injuries are most prevalent. Aims: To compare if the knee kinetics and kinematics in ACL injury recovered athletes return to the same level as those from an uninjured cohort during standard movements used for clinical assessment and badminton shots. Objectives: The objectives of the study were to determine: Knee valgus during the single leg squat, vertical drop jump, net shot and drop shot; Degree of internal or external rotation during the single leg squat, vertical drop jump, net shot and drop shot; Maximum knee flexion during the single leg squat, vertical drop jump and net shot. Methods: This case-control study included 14 participants with three ACL injury recovered athletes and 11 uninjured participants. The participants performed various functional tasks including vertical drop jump, single leg squat; the forehand net shot and the forehand drop shot. The data was analysed using the two-way ANOVA test, and the reliability of the data was evaluated using the Intra Class Coefficient. Results: The data showed a significant decrease in the range of knee rotation in ACL injured participants as compared to the uninjured cohort (F₇,₅₅₆=2.37; p=0.021). There was also a decrease in the maximum knee flexion angles and an increase in knee valgus angles in ACL injured participants although they were not statistically significant. Conclusion: There was a significant decrease in the knee rotation angles in the ACL injured participants which could be a potential cause for re-injury in these athletes in the future. Although the results for decrease in maximum knee flexion angles and increase in knee valgus angles were not significant, this may be due to a limited sample of ACL injured participants; there is potential for it to be identified as a variable of interest in the rehabilitation of ACL injuries. These changes in the knee biomechanics could be vital in the rehabilitation of ACL injured athletes in the future, and an inclusion of sports based tasks, e.g., Net shot along with standard protocol movements for ACL assessment would provide a better measure of the rehabilitation of the athlete.

Keywords: ACL, biomechanics, knee injury, racquet sport

Procedia PDF Downloads 158
267 Comparison between the Quadratic and the Cubic Linked Interpolation on the Mindlin Plate Four-Node Quadrilateral Finite Elements

Authors: Dragan Ribarić

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We employ the so-called problem-dependent linked interpolation concept to develop two cubic 4-node quadrilateral Mindlin plate finite elements with 12 external degrees of freedom. In the problem-independent linked interpolation, the interpolation functions are independent of any problem material parameters and the rotation fields are not expressed in terms of the nodal displacement parameters. On the contrary, in the problem-dependent linked interpolation, the interpolation functions depend on the material parameters and the rotation fields are expressed in terms of the nodal displacement parameters. Two cubic 4-node quadrilateral plate elements are presented, named Q4-U3 and Q4-U3R5. The first one is modelled with one displacement and two rotation degrees of freedom in every of the four element nodes and the second element has five additional internal degrees of freedom to get polynomial completeness of the cubic form and which can be statically condensed within the element. Both elements are able to pass the constant-bending patch test exactly as well as the non-zero constant-shear patch test on the oriented regular mesh geometry in the case of cylindrical bending. In any mesh shape, the elements have the correct rank and only the three eigenvalues, corresponding to the solid body motions are zero. There are no additional spurious zero modes responsible for instability of the finite element models. In comparison with the problem-independent cubic linked interpolation implemented in Q9-U3, the nine-node plate element, significantly less degrees of freedom are employed in the model while retaining the interpolation conformity between adjacent elements. The presented elements are also compared to the existing problem-independent quadratic linked-interpolation element Q4-U2 and to the other known elements that also use the quadratic or the cubic linked interpolation, by testing them on several benchmark examples. Simple functional upgrading from the quadratic to the cubic linked interpolation, implemented in Q4-U3 element, showed no significant improvement compared to the quadratic linked form of the Q4-U2 element. Only when the additional bubble terms are incorporated in the displacement and rotation function fields, which complete the full cubic linked interpolation form, qualitative improvement is fulfilled in the Q4-U3R5 element. Nevertheless, the locking problem exists even for the both presented elements, like in all pure displacement elements when applied to very thin plates modelled by coarse meshes. But good and even slightly better performance can be noticed for the Q4-U3R5 element when compared with elements from the literature, if the model meshes are moderately dense and the plate thickness not extremely thin. In some cases, it is comparable to or even better than Q9-U3 element which has as many as 12 more external degrees of freedom. A significant improvement can be noticed in particular when modeling very skew plates and models with singularities in the stress fields as well as circular plates with distorted meshes.

Keywords: Mindlin plate theory, problem-independent linked interpolation, problem-dependent interpolation, quadrilateral displacement-based plate finite elements

Procedia PDF Downloads 299
266 Computational Investigation on Structural and Functional Impact of Oncogenes and Tumor Suppressor Genes on Cancer

Authors: Abdoulie K. Ceesay

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Within the sequence of the whole genome, it is known that 99.9% of the human genome is similar, whilst our difference lies in just 0.1%. Among these minor dissimilarities, the most common type of genetic variations that occurs in a population is SNP, which arises due to nucleotide substitution in a protein sequence that leads to protein destabilization, alteration in dynamics, and other physio-chemical properties’ distortions. While causing variations, they are equally responsible for our difference in the way we respond to a treatment or a disease, including various cancer types. There are two types of SNPs; synonymous single nucleotide polymorphism (sSNP) and non-synonymous single nucleotide polymorphism (nsSNP). sSNP occur in the gene coding region without causing a change in the encoded amino acid, while nsSNP is deleterious due to its replacement of a nucleotide residue in the gene sequence that results in a change in the encoded amino acid. Predicting the effects of cancer related nsSNPs on protein stability, function, and dynamics is important due to the significance of phenotype-genotype association of cancer. In this thesis, Data of 5 oncogenes (ONGs) (AKT1, ALK, ERBB2, KRAS, BRAF) and 5 tumor suppressor genes (TSGs) (ESR1, CASP8, TET2, PALB2, PTEN) were retrieved from ClinVar. Five common in silico tools; Polyphen, Provean, Mutation Assessor, Suspect, and FATHMM, were used to predict and categorize nsSNPs as deleterious, benign, or neutral. To understand the impact of each variation on the phenotype, Maestro, PremPS, Cupsat, and mCSM-NA in silico structural prediction tools were used. This study comprises of in-depth analysis of 10 cancer gene variants downloaded from Clinvar. Various analysis of the genes was conducted to derive a meaningful conclusion from the data. Research done indicated that pathogenic variants are more common among ONGs. Our research also shows that pathogenic and destabilizing variants are more common among ONGs than TSGs. Moreover, our data indicated that ALK(409) and BRAF(86) has higher benign count among ONGs; whilst among TSGs, PALB2(1308) and PTEN(318) genes have higher benign counts. Looking at the individual cancer genes predisposition or frequencies of causing cancer according to our research data, KRAS(76%), BRAF(55%), and ERBB2(36%) among ONGs; and PTEN(29%) and ESR1(17%) among TSGs have higher tendencies of causing cancer. Obtained results can shed light to the future research in order to pave new frontiers in cancer therapies.

Keywords: tumor suppressor genes (TSGs), oncogenes (ONGs), non synonymous single nucleotide polymorphism (nsSNP), single nucleotide polymorphism (SNP)

Procedia PDF Downloads 73
265 Cycle-Oriented Building Components and Constructions Made from Paper Materials

Authors: Rebecca Bach, Evgenia Kanli, Nihat Kiziltoprak, Linda Hildebrand, Ulrich Knaack, Jens Schneider

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The building industry has a high demand for resources and at the same time is responsible for a significant amount of waste created worldwide. Today's building components need to contribute to the protection of natural resources without creating waste. This is defined in the product development phase and impacts the product’s degree of being cycle-oriented. Paper-based materials show advantage due to their renewable origin and their ability to incorporate different functions. Besides the ecological aspects like renewable origin and recyclability the main advantages of paper materials are its light-weight but stiff structure, the optimized production processes and good insulation values. The main deficits from building technology’s perspective are the material's vulnerability to humidity and water as well as inflammability. On material level, those problems can be solved by coatings or through material modification. On construction level intelligent setup and layering of a building component can improve and also solve these issues. The target of the present work is to provide an overview of developed building components and construction typologies mainly made from paper materials. The research is structured in four parts: (1) functions and requirements, (2) preselection of paper-based materials, (3) development of building components and (4) evaluation. As part of the research methodology at first the needs of the building sector are analyzed with the aim to define the main areas of application and consequently the requirements. Various paper materials are tested in order to identify to what extent the requirements are satisfied and determine potential optimizations or modifications, also in combination with other construction materials. By making use of the material’s potentials and solving the deficits on material and on construction level, building components and construction typologies are developed. The evaluation and the calculation of the structural mechanics and structural principals will show that different construction typologies can be derived. Profiles like paper tubes can be used at best for skeleton constructions. Massive structures on the other hand can be formed by plate-shaped elements like solid board or honeycomb. For insulation purposes corrugated cardboard or cellulose flakes have the best properties, while layered solid board can be applied to prevent inner condensation. Enhancing these properties by material combinations for instance with mineral coatings functional constructions mainly out of paper materials were developed. In summary paper materials offer a huge variety of possible applications in the building sector. By these studies a general base of knowledge about how to build with paper was developed and is to be reinforced by further research.

Keywords: construction typologies, cycle-oriented construction, innovative building material, paper materials, renewable resources

Procedia PDF Downloads 262
264 Sequential Pulsed Electric Field and Ultrasound Assisted Extraction of Bioactive Enriched Fractions from Button Mushroom Stalks

Authors: Bibha Kumari, Nigel P. Brunton, Dilip K. Rai, Brijesh K. Tiwari

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Edible mushrooms possess numerous functional components like homo- and hetero- β-glucans [β(1→3), β(1→4) and β(1→6) glucosidic linkages], chitins, ergosterols, bioactive polysaccharides and peptides imparting health beneficial properties to mushrooms. Some of the proven biological activities of mushroom extracts are antioxidant, antimicrobial, immunomodulatory, cholesterol lowering activity by inhibiting a key cholesterol metabolism enzyme i.e. 3-hydroxy-3-methyl-glutaryl CoA reductase (HMGCR), angiotensin I-converting enzyme (ACE) inhibition. Application of novel extraction technologies like pulsed electric field (PEF) and high power ultrasound offers clean, green, faster and efficient extraction alternatives with enhanced and good quality extracts. Sequential PEF followed by ultrasound assisted extraction (UAE) were applied to recover bioactive enriched fractions from industrial white button mushroom (Agaricus bisporus) stalk waste using environmentally friendly and GRAS solvents i.e. water and water/ethanol combinations. The PEF treatment was carried out at 60% output voltage, 2 Hz frequency for 500 pulses of 20 microseconds pulse width, using KCl salt solution of 0.6 mS/cm conductivity by the placing 35g of chopped fresh mushroom stalks and 25g of salt solution in the 4x4x4cm3 treatment chamber. Sequential UAE was carried out on the PEF pre-treated samples using ultrasonic-water-bath (USB) of three frequencies (25 KHz, 35 KHz and 45 KHz) for various treatment times (15-120 min) at 80°C. Individual treatment using either PEF or UAE were also investigation to compare the effect of each treatment along with the combined effect on the recovery and bioactivity of the crude extracts. The freeze dried mushroom stalk powder was characterised for proximate compositional parameters (dry weight basis) showing 64.11% total carbohydrate, 19.12% total protein, 7.21% total fat, 31.2% total dietary fiber, 7.9% chitin (as glucosamine equivalent) and 1.02% β-glucan content. The total phenolic contents (TPC) were determined by the Folin-Ciocalteu procedure and expressed as gallic-acid-equivalents (GAE). The antioxidant properties were ascertained using DPPH and FRAP assays and expressed as trolox-equivalents (TE). HMGCR activity and molecular mass of β-glucans will be measured using the commercial HMG-CoA Reductase Assay kit (Sigma-Aldrich) and size exclusion chromatography (HPLC-SEC), respectively. Effects of PEF, UAE and their combination on the antioxidant capacity, HMGCR inhibition and β-glucans content will be presented.

Keywords: β-glucan, mushroom stalks, pulsed electric field (PEF), ultrasound assisted extraction (UAE)

Procedia PDF Downloads 273
263 A Kunitz-Type Serine Protease Inhibitor from Rock Bream, Oplegnathus fasciatus Involved in Immune Responses

Authors: S. D. N. K. Bathige, G. I. Godahewa, Navaneethaiyer Umasuthan, Jehee Lee

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Kunitz-type serine protease inhibitors (KTIs) are identified in various organisms including animals, plants and microbes. These proteins shared single or multiple Kunitz inhibitory domains link together or associated with other types of domains. Characteristic Kunitz type domain composed of around 60 amino acid residues with six conserved cysteine residues to stabilize by three disulfide bridges. KTIs are involved in various physiological processes, such as ion channel blocking, blood coagulation, fibrinolysis and inflammation. In this study, two Kunitz-type domain containing protein was identified from rock bream database and designated as RbKunitz. The coding sequence of RbKunitz encoded for 507 amino acids with 56.2 kDa theoretical molecular mass and 5.7 isoelectric point (pI). There are several functional domains including MANEC superfamily domain, PKD superfamily domain, and LDLa domain were predicted in addition to the two characteristic Kunitz domain. Moreover, trypsin interaction sites were also identified in Kunitz domain. Homology analysis revealed that RbKunitz shared highest identity (77.6%) with Takifugu rubripes. Completely conserved 28 cysteine residues were recognized, when comparison of RbKunitz with other orthologs from different taxonomical groups. These structural evidences indicate the rigidity of RbKunitz folding structure to achieve the proper function. The phylogenetic tree was constructed using neighbor-joining method and exhibited that the KTIs from fish and non-fish has been evolved in separately. Rock bream was clustered with Takifugu rubripes. The SYBR Green qPCR was performed to quantify the RbKunitz transcripts in different tissues and challenged tissues. The mRNA transcripts of RbKunitz were detected in all tissues (muscle, spleen, head kidney, blood, heart, skin, liver, intestine, kidney and gills) analyzed and highest transcripts level was detected in gill tissues. Temporal transcription profile of RbKunitz in rock bream blood tissues was analyzed upon LPS (lipopolysaccharide), Poly I:C (Polyinosinic:polycytidylic acid) and Edwardsiella tarda challenge to understand the immune responses of this gene. Compare to the unchallenged control RbKunitz exhibited strong up-regulation at 24 h post injection (p.i.) after LPS and E. tarda injection. Comparatively robust expression of RbKunits was observed at 3 h p.i. upon Poly I:C challenge. Taken together all these data indicate that RbKunitz may involve into to immune responses upon pathogenic stress, in order to protect the rock bream.

Keywords: Kunitz-type, rock bream, immune response, serine protease inhibitor

Procedia PDF Downloads 362
262 Obtaining Composite Cotton Fabric by Cyclodextrin Grafting

Authors: U. K. Sahin, N. Erdumlu, C. Saricam, I. Gocek, M. H. Arslan, H. Acikgoz-Tufan, B. Kalav

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Finishing is an important part of fabric processing with which a wide range of features are imparted to greige or colored fabrics for various end-uses. Especially, by the addition or impartation of nano-scaled particles to the fabric structure composite fabrics, a kind of composite materials can be acquired. Composite materials, generally shortened as composites or in other words composition materials, are engineered or naturally occurring materials made from two or more component materials with significantly different physical, mechanical or chemical characteristics remaining separate and distinctive at the macroscopic or microscopic scale within the end product structure. Therefore, the technique finishing which is one of the fundamental methods to be applied on fabrics for obtainment of composite fabrics with many functionalities was used in the current study with the same purpose. However, regardless of the finishing materials applied, the efficient life of finished product on offering desired feature is low, since the durability of finishes on the material is limited. Any increase in durability of these finishes on textiles would enhance the life of use for textiles, which will result in happier users. Therefore, in this study, since higher durability was desired for the finishing materials fixed on the fabrics, nano-scaled hollow structured cyclodextrins were chemically imparted by grafting to the structure of conventional cotton fabrics by the help of finishing technique in order to be fixed permanently. By this way, a processed and functionalized base fabric having potential to be treated in the subsequent processes with many different finishing agents and nanomaterials could be obtained. Henceforth, this fabric can be used as a multi-functional fabric due to the encapturing ability of cyclodextrins to molecules/particles via physical/chemical means. In this study, scoured and rinsed woven bleached plain weave 100% cotton fabrics were utilized because textiles made of cotton are the most demanded textile products in the textile market by the textile consumers in daily life. Cotton fabric samples were immersed in treating baths containing β-cyclodextrin and 1,2,3,4-butanetetracarboxylic acid and to reduce the curing temperature the catalyst sodium hypophosphite monohydrate was used. All impregnated fabric samples were pre-dried. The reaction of grafting was performed in dry state. The treated and cured fabric samples were rinsed with warm distilled water and dried. The samples were dried for 4 h and weighed before and after finishing and rinsing. Stability and durability of β-cyclodextrins on fabric surface against external factors such as washing as well as strength of functionalized fabric in terms of tensile and tear strength were tested. Presence and homogeneity of distribution of β-cyclodextrins on fabric surface were characterized.

Keywords: cotton fabric, cyclodextrine, improved durability, multifunctional composite textile

Procedia PDF Downloads 275
261 Land Transfer for New Township and Its Impact from Dwellers' Point of View: A Case Study of New Town Kolkata

Authors: Subhra Chattopadhyay

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New Towns are usually built up at city-periphery with an eye to accommodate overspill population and functions of the city. ‘New towns are self-sufficient planned towns having a full range of urban economic and social activities, so it can provide employments for all of its inhabitants as well as a balanced self-content social community could be maintained’. In 3rd world countries New towns often emerge from scratch i.e on the area having no urban background and therefore, it needs a massive land conversion from rural to urban. This paper aims to study the implication of such land title transfer into rural sustainability with a case study at Jatragachi, New Town Kolkata. Broad objectives of this study are to understand 1. new changes in this area like i)changes in land use, ii) demographic changes, iii) occupational changes of the local people and 2.their view about new town planning. Major observations are stated below. The studied area was completely rural till recent years and is now at the heart of New Town Kolkata. Though this area is now under the jurisdiction of New Town Kolkata Development Authority (NKDA), it is still administrated by rural self-government.It creates administrative confusion and misuse of public capital. It is observed in this study that cultivation was the mainstay of livelihood for the majority of residents till recent past. There was a dramatic rise in irrigated area in the decade of 90’s pointing out agricultural prosperity.The area achieved the highest productivity of rice in the District. Percentage of marginal workers dropped significantly.In addition to it, ascending women’s literacy rate as found in this rural Mouza obviously indicates a constant social progress .Through land conversion, this flourishing agricultural land has been transformed into urban area with highly sophisticated uses. Such development may satisfy educated urban elite but the dwellers of the area suffer a lot. They bear the cost of new town planning through loss of their assured food and income as well as their place identity. The number of marginal workers increases abruptly. The growth of female literacy drops down. The area loses its functional linkages with its surroundings and fails to prove its actual growth potentiality. The physical linkages( like past roads and irrigation infrastructure) which had developed through time to support the economy become defunct. The ecological services which were provided by the agricultural field are denied. The historicity of this original site is demolished. Losses of the inhabitants of the area who have been evicted are also immense and cannot be materially compensated. Therefore, the ethos of such new town planning in stake of rural sustainability is under question. Need for an integrated approach for rural and urban development planning is felt in this study.

Keywords: new town, sustainable development, growth potentiality, land transfer

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260 The M Health Paradigm for the Chronic Care Management of Obesity: New Opportunities in Clinical Psychology and Medicine

Authors: Gianluca Castelnuovo, Gian Mauro Manzoni, Giada Pietrabissa, Stefania Corti, Emanuele Giusti, Roberto Cattivelli, Enrico Molinari, Susan Simpson

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Obesity is currently an important public health problem of epidemic proportions (globesity). Moreover Binge Eating Disorder (BED) is typically connected with obesity, even if not occurring exclusively in conjunction with overweight conditions. Typically obesity with BED requires a longer term treatment in comparison with simple obesity. Rehabilitation interventions that aim at improving weight-loss, reducing obesity-related complications and changing dysfunctional behaviors, should ideally be carried out in a multidisciplinary context with a clinical team composed of psychologists, dieticians, psychiatrists, endocrinologists, nutritionists, physiotherapists, etc. Long-term outpatient multidisciplinary treatments are likely to constitute an essential aspect of rehabilitation, due to the growing costs of a limited inpatient approach. Internet-based technologies can improve long-term obesity rehabilitation within a collaborative approach. The new m health (m-health, mobile health) paradigm, defined as clinical practices supported by up to date mobile communication devices, could increase compliance- engagement and contribute to a significant cost reduction in BED and obesity rehabilitation. Five psychological components need to be considered for successful m Health-based obesity rehabilitation in order to facilitate weight-loss.1) Self-monitoring. Portable body monitors, pedometers and smartphones are mobile and, therefore, can be easily used, resulting in continuous self-monitoring. 2) Counselor feedback and communication. A functional approach is to provide online weight-loss interventions with brief weekly or monthly counselor or psychologist visits. 3) Social support. A group treatment format is typically preferred for behavioral weight-loss interventions. 4) Structured program. Technology-based weight-loss programs incorporate principles of behavior therapy and change with structured weekly protocolos including nutrition, exercise, stimulus control, self-regulation strategies, goal-setting. 5) Individually tailored program. Interventions specifically designed around individual’s goals typically record higher rates of adherence and weight loss. Opportunities and limitations of m health approach in clinical psychology for obesity and BED are discussed, taking into account future research directions in this promising area.

Keywords: obesity, rehabilitation, out-patient, new technologies, tele medicine, tele care, m health, clinical psychology, psychotherapy, chronic care management

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259 Efficient Synthesis of Highly Functionalized Biologically Important Spirocarbocyclic Oxindoles via Hauser Annulation

Authors: Kanduru Lokesh, Venkitasamy Kesavan

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The unique structural features of spiro-oxindoles with diverse biological activities have made them privileged structures in new drug discovery. The key structural characteristic of these compounds is the spiro ring fused at the C-3 position of the oxindole core with varied heterocyclic motifs. Structural diversification of heterocyclic scaffolds to synthesize new chemical entities as pharmaceuticals and agrochemicals is one of the important goals of synthetic organic chemists. Nitrogen and oxygen containing heterocycles are by far the most widely occurring privileged structures in medicinal chemistry. The structural complexity and distinct three-dimensional arrangement of functional groups of these privileged structures are generally responsible for their specificity against biological targets. Structurally diverse compound libraries have proved to be valuable assets for drug discovery against challenging biological targets. Thus, identifying a new combination of substituents at C-3 position on oxindole moiety is of great importance in drug discovery to improve the efficiency and efficacy of the drugs. The development of suitable methodology for the synthesis of spiro-oxindole compounds has attracted much interest often in response to the significant biological activity displayed by the both natural and synthetic compounds. So creating structural diversity of oxindole scaffolds is need of the decade and formidable challenge. A general way to improve synthetic efficiency and also to access diversified molecules is through the annulation reactions. Annulation reactions allow the formation of complex compounds starting from simple substrates in a single transformation consisting of several steps in an ecologically and economically favorable way. These observations motivated us to develop the annulation reaction protocol to enable the synthesis of a new class of spiro-oxindole motifs which in turn would enable the enhancement of molecular diversity. As part of our enduring interest in the development of novel, efficient synthetic strategies to enable the synthesis of biologically important oxindole fused spirocarbocyclic systems, We have developed an efficient methodology for the construction of highly functionalized spirocarbocyclic oxindoles through [4+2] annulation of phthalides via Hauser annulation. functionalized spirocarbocyclic oxindoles was accomplished for the first time in the literature using Hauser annulation strategy. The reaction between methyleneindolinones and arylsulfonylphthalides catalyzed by cesium carbonate led to the access of new class of biologically important spiro[indoline-3,2'-naphthalene] derivatives in very good yields. The synthetic utility of the annulated product was further demonstrated by fluorination Using NFSI as a fluorinating agent to furnish corresponding fluorinated product.

Keywords: Hauser-Kraus annulation, spiro carbocyclic oxindoles, oxindole-ester, fluoridation

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258 Poly(ε-Caprolactone)-Based Bilayered Scaffolds Prepared by Electrospinning for Tissue Engineering of Small-Diameter Vascular Grafts

Authors: Mohammed Fayez Al Rez

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Nowadays, there is an unmet clinical need for new small-diameter vascular grafts to overcome the drawbacks of traditional methods used for treatment of widespread cardiovascular diseases. Vascular tissue engineering (VTE) is a promising approach that can be utilized to develop viable vascular grafts by in vitro seeding of functional cells onto a scaffold allowing them to attach, proliferate and differentiate. To achieve this purpose, the scaffold should provide cells with the initial necessary extracellular matrix environment and structure until being able to reconstruct the required vascular tissue. Therefore, producing scaffolds with suitable features is crucial for guiding cells properly to develop the desired tissue-engineered vascular grafts for clinical applications. The main objective of this work is fabrication and characterization of tubular small-diameter ( < 6 mm) bilayered scaffolds for VTE. The scaffolds were prepared via mixing electrospinning approach of biodegradable poly(ε-caprolactone) (PCL) polymer – due to its favorable physicochemical properties – to mimic the natural environment-extracellular matrix. Firstly, tubular nanofibrous construct with inner diameter of 3, 4 or 5 mm was electrospun as inner layer, and secondly, microfibrous construct was electrospun as outer layer directly on the first produced inner layer. To improve the biological properties of PCL, a group of the electrospun scaffolds was immersed in type-1 collagen solution. The morphology and structure of the resulting fibrous scaffolds were investigated by scanning electron microscope. The electrospun nanofibrous inner layer contained fibers measuring 219±35 nm in diameter, while the electrospun microfibrous outer layer contained fibers measuring 1011 ± 150 nm. Furthermore, mechanical, thermal and physical tests were conducted with both electrospun bilayered scaffold types where revealed improved properties. Biological investigations using endothelial, smooth muscle and fibroblast cell line showed good biocompatibility of both tested electrospun scaffolds. Better attachment and proliferation were obviously found when cells were cultured on the scaffolds immersed with collagen due to increasing the hydrophilicity of the PCL. The easy, inexpensive and versatile electrospinning approach used in this work was able to successfully produce double layered tubular elastic structures containing both nanofibers and microfibers to imitate the native vascular structure. The PCL – as a suitable and approved biomaterial for many biomedical and tissue engineering applications – can ensure favorable mechanical properties of scaffolds used for VTE. The VTE approach using electrospun bilayered scaffolds offers optimal solutions and holds significant promises for treatment of many cardiovascular diseases.

Keywords: electrospinning, poly(ε-caprolactone) (PCL), tissue-engineered vascular graft, tubular bilayered scaffolds, vascular cells

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257 Bio-Oil Compounds Sorption Enhanced Steam Reforming

Authors: Esther Acha, Jose Cambra, De Chen

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Hydrogen is considered an important energy vector for the 21st century. Nowadays there are some difficulties for hydrogen economy implantation, and one of them is the high purity required for hydrogen. This energy vector is still being mainly produced from fuels, from wich hydrogen is produced as a component of a mixture containing other gases, such as CO, CO2 and H2O. A forthcoming sustainable pathway for hydrogen is steam-reforming of bio-oils derived from biomass, e.g. via fast pyrolysis. Bio-oils are a mixture of acids, alcohols, aldehydes, esters, ketones, sugars phenols, guaiacols, syringols, furans, multi-functional compounds and also up to a 30 wt% of water. The sorption enhanced steam reforming (SESR) process is attracting a great deal of attention due to the fact that it combines both hydrogen production and CO2 separation. In the SESR process, carbon dioxide is captured by an in situ sorbent, which shifts the reversible reforming and water gas shift reactions to the product side, beyond their conventional thermodynamic limits, giving rise to a higher hydrogen production and lower cost. The hydrogen containing mixture has been obtained from the SESR of bio-oil type compounds. Different types of catalysts have been tested. All of them contain Ni at around a 30 wt %. Two samples have been prepared with the wet impregnation technique over conventional (gamma alumina) and non-conventional (olivine) supports. And a third catalysts has been prepared over a hydrotalcite-like material (HT). The employed sorbent is a commercial dolomite. The activity tests were performed in a bench-scale plant (PID Eng&Tech), using a stainless steel fixed bed reactor. The catalysts were reduced in situ in the reactor, before the activity tests. The effluent stream was cooled down, thus condensed liquid was collected and weighed, and the gas phase was analysed online by a microGC. The hydrogen yield, and process behavior was analysed without the sorbent (the traditional SR where a second purification step will be needed but that operates in steady state) and the SESR (where the purification step could be avoided but that operates in batch state). The influence of the support type and preparation method will be observed in the produced hydrogen yield. Additionally, the stability of the catalysts is critical, due to the fact that in SESR process sorption-desorption steps are required. The produced hydrogen yield and hydrogen purity has to be high and also stable, even after several sorption-desorption cycles. The prepared catalysts were characterized employing different techniques to determine the physicochemical properties of the fresh-reduced and used (after the activity tests) materials. The characterization results, together with the activity results show the influence of the catalysts preparation method, calcination temperature, or can even explain the observed yield and conversion.

Keywords: CO2 sorbent, enhanced steam reforming, hydrogen

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256 Approaching a Tat-Rev Independent HIV-1 Clone towards a Model for Research

Authors: Walter Vera-Ortega, Idoia Busnadiego, Sam J. Wilson

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Introduction: Human Immunodeficiency Virus type 1 (HIV-1) is responsible for the acquired immunodeficiency syndrome (AIDS), a leading cause of death worldwide infecting millions of people each year. Despite intensive research in vaccine development, therapies against HIV-1 infection are not curative, and the huge genetic variability of HIV-1 challenges to drug development. Current animal models for HIV-1 research present important limitations, impairing the progress of in vivo approaches. Macaques require a CD8+ depletion to progress to AIDS, and the maintenance cost is high. Mice are a cheaper alternative but need to be 'humanized,' and breeding is not possible. The development of an HIV-1 clone able to replicate in mice is a challenging proposal. The lack of human co-factors in mice impedes the function of the HIV-1 accessory proteins, Tat and Rev, hampering HIV-1 replication. However, Tat and Rev function can be replaced by constitutive/chimeric promoters, codon-optimized proteins and the constitutive transport element (CTE), generating a novel HIV-1 clone able to replicate in mice without disrupting the amino acid sequence of the virus. By minimally manipulating the genomic 'identity' of the virus, we propose the generation of an HIV-1 clone able to replicate in mice to assist in antiviral drug development. Methods: i) Plasmid construction: The chimeric promoters and CTE copies were cloned by PCR using lentiviral vectors as templates (pCGSW and pSIV-MPCG). Tat mutants were generated from replication competent HIV-1 plasmids (NHG and NL4-3). ii) Infectivity assays: Retroviral vectors were generated by transfection of human 293T cells and murine NIH 3T3 cells. Virus titre was determined by flow cytometry measuring GFP expression. Human B-cells (AA-2) and Hela cells (TZMbl) were used for infectivity assays. iii) Protein analysis: Tat protein expression was determined by TZMbl assay and HIV-1 capsid by western blot. Results: We have determined that NIH 3T3 cells are able to generate HIV-1 particles. However, they are not infectious, and further analysis needs to be performed. Codon-optimized HIV-1 constructs are efficiently made in 293T cells in a Tat and Rev independent manner and capable of packaging a competent genome in trans. CSGW is capable of generating infectious particles in the absence of Tat and Rev in human cells when 4 copies of the CTE are placed preceding the 3’LTR. HIV-1 Tat mutant clones encoding different promoters are functional during the first cycle of replication when Tat is added in trans. Conclusion: Our findings suggest that the development of an HIV-1 Tat-Rev independent clone is challenging but achievable aim. However, further investigations need to be developed prior presenting our HIV-1 clone as a candidate model for research.

Keywords: codon-optimized, constitutive transport element, HIV-1, long terminal repeats, research model

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255 Multimodal Ophthalmologic Evaluation Can Detect Retinal Injuries in Asymptomatic Patients With Primary Antiphospholipid Syndrome

Authors: Taurino S. R. Neto, Epitácio D. S. Neto, Flávio Signorelli, Gustavo G. M. Balbi, Alex H. Higashi, Mário Luiz R. Monteiro, Eloisa Bonfá, Danieli C. O. Andrade, Leandro C. Zacharias

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Purpose: To perform a multimodal evaluation, including the use of Optical Coherence Angiotomography (OCTA), in patients with primary antiphospholipid syndrome (PAPS) without ocular complaints and to compare them with healthy individuals. Methods: A complete structural and functional ophthalmological evaluation using OCTA and microperimetry (MP) exam in patients with PAPS, followed at a tertiary rheumatology outpatient clinic, was performed. All ophthalmologic manifestations were recorded and then statistical analysis was performed for comparative purposes; p <0.05 was considered statistically significant. Results: 104 eyes of 52 subjects (26 patients with PAPS without ocular complaints and 26 healthy individuals) were included. Among PAPS patients, 21 were female (80.8%) and 21 (80.8%) were Caucasians. Thrombotic PAPS was the main clinical criteria manifestation (100%); 65.4% had venous and 34.6% had arterial thrombosis. Obstetrical criteria were present in 34.6% of all thrombotic PAPS patients. Lupus anticoagulant was present in all patients. 19.2% of PAPS patients presented ophthalmologic findings against none of the healthy individuals. The most common retinal change was paracentral acute middle maculopathy (PAMM) (3 patients, 5 eyes), followed by drusen-like deposits (1 patient, 2 eyes) and pachychoroid pigment epitheliopathy (1 patient, 1 eye). Systemic hypertension and hyperlipidaemia were present in 100% of the PAPS patients with PAMM, while only six patients (26.1%) with PAPS without PAMM presented these two risk factors together. In the quantitative OCTA evaluation, we found significant differences between PAPS patients and controls in both the superficial vascular complex (SVC) and deep vascular complex (DVC) in the high-speed protocol, as well as in the SVC in the high-resolution protocol. In the analysis of the foveal avascular zone (FAZ) parameters, the PAPS group had a larger area of FAZ in the DVC using the high-speed method compared to the control group (p=0.047). In the quantitative analysis of the MP, the PAPS group had lower central (p=0.041) and global (p<0.001) retinal sensitivity compared to the control group, as well as in the sector analysis, with the exception of the inferior sector. In the quantitative evaluation of fixation stability, there was a trend towards worse stability in the PAPS subgroup with PAMM in both studied methods. Conclusions: PAMM was observed in 11.5% of PAPS patients with no previous ocular complaints. Systemic hypertension concomitant with hyperlipidemia was the most commonly associated risk factor for PAMM in patients with PAPS. PAPS patients present lower vascular density and retinal sensitivity compared to the control group, even in patients without PAMM.

Keywords: antiphospholipid syndrome, optical coherence angio tomography, optical coherence tomography, retina

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