Search results for: bearing fault prognostics

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

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

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

Procedia PDF Downloads 344

Authors: Lola T. Alimkhodjaeva, Lola T. Zakirova, Soniya S. Ziyavidenova

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Background: Breast cancer (BC) is still one of the urgent oncology problems. The essential obstacle to the full anti-tumor therapy implementation is drug resistance development. Taking into account the fact that chemotherapy is main antitumor treatment in BC patients, the important task is to improve treatment results. Certain success in overcoming this situation has been associated with the use of methods of extracorporeal blood treatment (ECBT), plasmapheresis. Materials and Methods: We examined 129 women with resistant BC stages 3-4, aged between 56 to 62 years who had previously received 2 courses of CAF chemotherapy. All patients additionally underwent 2 courses of CAF chemotherapy but against the background ECBT with ultrasonic exposure. We studied the following parameters: 1. The highlights of peripheral blood before and after therapy. 2. The state of cellular immunity and identification of activation markers CD23 +, CD25 +, CD38 +, CD95 + on lymphocytes was performed using monoclonal antibodies. Evaluation of humoral immunity was determined by the level of main classes of immunoglobulins IgG, IgA, IgM in serum. 3. The degree of tumor regression was assessed by WHO recommended 4 gradations. (complete - 100%, partial - more than 50% of initial size, process stabilization–regression is less than 50% of initial size and tumor advance progressing). 4. Medical pathomorphism in the tumor was determined by Lavnikova. 5. The study of immediate and remote results, up to 3 years and more. Results and Discussion: After performing extracorporeal blood treatment anemia occurred in 38.9%, leukopenia in 36.8%, thrombocytopenia in 34.6%, hypolymphemia in 26.8%. Studies of immunoglobulin fractions in blood serum were able to establish a certain relationship between the classes of immunoglobulin A, G, M and their functions. The results showed that after treatment the values of main immunoglobulins in patients’ serum approximated to normal. Analysis of expression of activation markers CD25 + cells bearing receptors for IL-2 (IL-2Rα chain) and CD95 + lymphocytes that were mediated physiological apoptosis showed the tendency to increase, which apparently was due to activation of cellular immunity cytokines allocated by ultrasonic treatment. To carry out ECBT on the background of ultrasonic treatment improved the parameters of the immune system, which were expressed in stimulation of cellular immunity and correcting imbalances in humoral immunity. The key indicator of conducted treatment efficiency is the immediate result measured by the degree of tumor regression. After ECBT performance the complete regression was 10.3%, partial response - 55.5%, process stabilization - 34.5%, tumor advance progressing no observed. Morphological investigations of tumor determined therapeutic pathomorphism grade 2 in 15%, in 25% - grade 3 and therapeutic pathomorphism grade 4 in 60% of patients. One of the main criteria for the effect of conducted treatment is to study the remission terms in the postoperative period (up to 3 years or more). The remission terms up to 3 years with ECBT was 34.5%, 5-year survival was 54%. Carried out research suggests that a comprehensive study of immunological and clinical course of breast cancer allows the differentiated approach to the choice of methods for effective treatment.

Keywords: breast cancer, immunoglobulins, extracorporeal blood treatment, chemotherapy

Procedia PDF Downloads 243

Authors: U.K. Sarkar, G. Karnatak, P. Mishal, Lianthuamluaia, S. Kumari, S.K. Das, B.K. Das

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Inland open water fisheries provide food, income, livelihood and nutritional security to millions of fishers across the globe. However, the open water ecosystem and fisheries are threatened due to climate change and anthropogenic pressures, which are more visible in the recent six decades, making the resources vulnerable. Understanding the interaction between meteorological parameters and inland fisheries is imperative to develop mitigation and adaptation strategies. As per IPCC 5th assessment report, the earth is warming at a faster rate in recent decades. Global mean surface temperature (GMST) for the decade 2006–2015 (0.87°C) was 6 times higher than the average over the 1850–1900 period. The direct and indirect impacts of climatic parameters on the ecology of fisheries ecosystem have a great bearing on fisheries due to alterations in fish physiology. The impact of meteorological factors on ecosystem health and fish food organisms brings about changes in fish diversity, assemblage, reproduction and natural recruitment. India’s average temperature has risen by around 0.7°C during 1901–2018. The studies show that the mean air temperature in the Ganga basin has increased in the range of 0.20 - 0.47 °C and annual rainfall decreased in the range of 257-580 mm during the last three decades. The studies clearly indicate visible impacts of climatic and environmental factors on inland open water fisheries. Besides, a significant reduction in-depth and area (37.20–57.68% reduction), diversity of natural indigenous fish fauna (ranging from 22.85 to 54%) in wetlands and progression of trophic state from mesotrophic to eutrophic were recorded. In this communication, different applications of biometeorology in inland fisheries management with special reference to the assessment of ecosystem and species vulnerability to climatic variability and change have been discussed. Further, the paper discusses the impact of climate anomaly and extreme climatic events on inland fisheries and emphasizes novel modeling approaches for understanding the impact of climatic and environmental factors on reproductive phenology for identification of climate-sensitive/resilient fish species for the adoption of climate-smart fisheries in the future. Adaptation and mitigation strategies to enhance fish production and the role of culture-based fisheries and enclosure culture in converting sequestered carbon into blue carbon have also been discussed. In general, the type and direction of influence of meteorological parameters on fish biology in open water fisheries ecosystems are not adequately understood. The optimum range of meteorological parameters for sustaining inland open water fisheries is yet to be established. Therefore, the application of biometeorology in inland fisheries offers ample scope for understanding the dynamics in changing climate, which would help to develop a database on such least, addressed research frontier area. This would further help to project fisheries scenarios in changing climate regimes and develop adaptation and mitigation strategies to cope up with adverse meteorological factors to sustain fisheries and to conserve aquatic ecosystem and biodiversity.

Keywords: biometeorology, inland fisheries, aquatic ecosystem, modeling, India

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Authors: Mark McGuire, Eric Shannon, John Parmigiani

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Timber harvesting increasingly involves mechanized equipment. This has increased the efficiency of harvesting, but has also introduced worker-safety concerns. One such concern arises from the use of harvesters. During operation, harvesters subject saw chain to large dynamic mechanical stresses. These stresses can, under certain conditions, cause the saw chain to fracture. The high speed of harvester saw chain can cause the resulting open chain loop to fracture a second time due to the dynamic loads placed upon it as it travels through space. If a second fracture occurs, it can result in a projectile consisting of one-to-several chain links. This projectile is referred to as a chain shot. It has speeds similar to a bullet but typically has greater mass and is a significant safety concern. Numerous examples exist of chain shots penetrating bullet-proof barriers and causing severe injury and death. Improved harvester-cab barriers can help prevent injury however a comprehensive scientific understanding of chain shot is required to consistently reduce or prevent it. Obtaining this understanding requires a test machine with the capability to cause chain shot to occur under carefully controlled conditions and accurately measure the response. Worldwide few such test machine exist. Those that do focus on validating the ability of barriers to withstand a chain shot impact rather than obtaining a scientific understanding of the chain shot event itself. The purpose of this paper is to describe the design, fabrication, and use of a test machine capable of a comprehensive scientific investigation of chain shot. The capabilities of this machine are to test all commercially-available saw chains and bars at chain tensions and speeds meeting and exceeding those typically encountered in harvester use and accurately measure the corresponding key technical parameters. The test machine was constructed inside of a standard shipping container. This provides space for both an operator station and a test chamber. In order to contain the chain shot under any possible test conditions, the test chamber was lined with a base layer of AR500 steel followed by an overlay of HDPE. To accommodate varying bar orientations and fracture-initiation sites, the entire saw chain drive unit and bar mounting system is modular and capable of being located anywhere in the test chamber. The drive unit consists of a high-speed electric motor with a flywheel. Standard Ponsse harvester head components are used to bar mounting and chain tensioning. Chain lubrication is provided by a separate peristaltic pump. Chain fracture is initiated through ISO standard 11837. Measure parameters include shaft speed, motor vibration, bearing temperatures, motor temperature, motor current draw, hydraulic fluid pressure, chain force at fracture, and high-speed camera images. Results show that the machine is capable of consistently causing chain shot. Measurement output shows fracture location and the force associated with fracture as a function of saw chain speed and tension. Use of this machine will result in a scientific understanding of chain shot and consequently improved products and greater harvester operator safety.

Keywords: chain shot, safety, testing, timber harvesters

Procedia PDF Downloads 123

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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Authors: Emily Moore, Andrew Gaukroger, Matthew Solan, Lucy Bailey, Alexandra Boxall, Andrew Carne, Chintu Gadamsetty, Charlotte Morley, Katy Western, Iwona Kolodziejczyk

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Introduction: Rupture of the Achilles tendon is common and has a long recovery period. Most cases are managed non-operatively. Foot and Ankle Surgeons advise an ultrasound scan to check the gap between the torn ends. A large gap (with the ankle in equinus) is a relative indication for surgery. The definitive decision regarding surgical versus non-operative management can only be made once an ultrasound scan is undertaken and the patient is subsequently reviewed by a Foot and Ankle surgeon. To get to this point, the patient journey involves several hospital departments. In nearby trusts, patients reattend for a scan and go to the plaster room both before and after the ultrasound for removal and re-application of the cast. At a third visit to the hospital, the surgeon and patient discuss options for definitive treatment. It may take 2-3 weeks from the initial Emergency Department visit before the final treatment decision is made. This “wasted time” is ultimately added to the recovery period for the patient. In this hospital, Achilles rupture patients are seen in a weekly multidisciplinary OneStop Heel Pain clinic. This pathway was already efficient but subject to occasional frustrating delays if a key staff member was absent. A new pathway was introduced with the goal to reduce delays to a definitive treatment plan. Method: A retrospective series of Achilles tendon ruptures managed according to the 2019 protocol was identified. Time taken from the Emergency Department to have both an ultrasound scan and specialist Foot and Ankle surgical review were calculated. 30 consecutive patients were treated with our new pathway and prospectively followed. The time taken for a scan and for specialist review were compared to the 30 consecutive cases from the 2019 (pre-COVID) cohort. The new pathway includes 1. A new contoured splint applied to the front of the injured limb held with a bandage. This can be removed and replaced (unlike a plaster cast) in the ultrasound department, removing the need for plaster room visits. 2. Urgent triage to a Foot and Ankle specialist. 3. Ultrasound scan for assessment of rupture gap and deep vein thrombosis check. 4. Early decision regarding surgery. Transfer to weight bearing in a prosthetic boot in equinuswithout waiting for the once-a-week clinic. 5. Extended oral VTE prophylaxis. Results: The time taken for a patient to have both an ultrasound scan and specialist review fell > 50%. All patients in the new pathway reached a definitive treatment decision within one week. There were no significant differences in patient demographics or rates of surgical vs non-operative treatment. The mean time from Emergency Department visit to specialist review and ultrasound scan fell from 8.7 days (old protocol) to 2.9 days (new pathway). The maximum time for this fell from 23 days (old protocol) to 6 days (new pathway). Conclusion: Teamwork and innovation have improved the experience for patients with an Achilles tendon rupture. The new pathway brings many advantages - reduced time in the Emergency Department, fewer hospital visits, less time using crutches and reduced overall recovery time.

Keywords: orthopaedics, achilles rupture, ultrasound, innovation

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Authors: Ennios Eros Giogos, Nefeli Katsarou, Giota Mantziorou, Elena Panou, Nikolaos Kourniatis, Socratis Giannoudis

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In the context of the postgraduate course Productive Design, Department of Interior Architecture of the University of West Attica in Athens, under the guidance of Professors Nikolaos Koyrniatis and Socratis Giannoudis, kinetic mechanisms with parametric models were examined for their further application in the design of objects. In the first phase, the students studied a motion mechanism that they chose from daily experience and then analyzed its geometric structure in relation to the geometric transformations that exist. In the second phase, the students tried to design it through a parametric model in Grasshopper3d for Rhino algorithmic processor and plan the design of its application in an everyday object. For the project presented, our team began by studying the movement of living beings, specifically the snake. By studying the snake and the role that the environment has in its movement, four basic typologies were recognized: serpentine, concertina, sidewinding and rectilinear locomotion, as well as its ability to perform spiral formations. Most typologies are characterized by ripples, a series of sinusoidal curves. For the application of the snake movement in a polymorphic space divider, the use of a coil-type joint was studied. In the Grasshopper program, the simulation of the desired motion for the polymorphic surface was tested by applying a coil on a sinusoidal curve and a spiral curve. It was important throughout the process that the points corresponding to the nodes of the real object remain constant in number, as well as the distances between them and the elasticity of the construction had to be achieved through a modular movement of the coil and not some elastic element (material) at the nodes. Using mesh (repeating coil), the whole construction is transformed into a supporting body and combines functionality with aesthetics. The set of elements functions as a vertical spatial network, where each element participates in its coherence and stability. Depending on the positions of the elements in terms of the level of support, different perspectives are created in terms of the visual perception of the adjacent space. For the implementation of the model on the scale (1:3), (0.50m.x2.00m.), the load-bearing structure that was studied has aluminum rods for the basic pillars Φ6mm and Φ 2.50 mm, for the secondary columns. Filling elements and nodes are of similar material and were made of MDF surfaces. During the design process, four trapezoidal patterns were picketed, which function as filling elements, while in order to support their assembly, a different engraving facet was done. The nodes have holes that can be pierced by the rods, while their connection point with the patterns has a half-carved recess. The patterns have a corresponding recess. The nodes are of two different types depending on the column that passes through them. The patterns and knots were designed to be cut and engraved using a Laser Cutter and attached to the knots using glue. The parameters participate in the design as mechanisms that generate complex forms and structures through the repetition of constantly changing versions of the parts that compose the object.

Keywords: polymorphic, locomotion, sinusoidal curves, parametric

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Authors: Ram Sharma, Esha Chatterjee, Santosh Kumar Guru, Kunal Nepali

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A tractable anti-lung cancer agent was identified via the installation of a Ring C expanded synthetic analogue of the alkaloid vasicinone [7,8,9,10-tetrahydroazepino[2,1-b] quinazolin-12(6H)-one (TAZQ)] as a surface recognition part in the HDAC inhibitory three-component model. Noteworthy to mention that the candidature of TAZQ was deemed suitable for accommodation in HDAC inhibitory pharmacophore as per the results of the fragment recruitment process conducted by our laboratory. TAZQ was pinpointed through the fragment screening program as a synthetically flexible fragment endowed with some moderate cell growth inhibitory activity against the lung cancer cell lines, and it was anticipated that the use of the aforementioned fragment to generate hydroxamic acid functionality (zinc-binding motif) bearing HDAC inhibitors would boost the antitumor efficacy of TAZQ. Consistent with our aim of applying epigenetic targets to the treatment of lung cancer, a strikingly potent anti-lung cancer scaffold (compound 6) was pinpointed through a series of in-vitro experiments. Notably, the compounds manifested a magnificent activity profile against KRAS and EGFR mutant lung cancer cell lines (IC50 = 0.80 - 0.96 µM), and the effects were found to be mediated through preferential HDAC6 inhibition (IC50 = 12.9 nM). In addition to HDAC6 inhibition, the compounds also elicited HDAC1 and HDAC3 inhibitory activity with an IC50 value of 49.9 nM and 68.5 nM, respectively. The HDAC inhibitory ability of compound 6 was also confirmed from the results of the western blot experiment that revealed its potential to decrease the expression levels of HDAC isoforms (HDAC1, HDAC3, and HDAC6). Noteworthy to mention that complete downregulation of the HDAC6 isoform was exerted by compound 6 at 0.5 and 1 µM. Moreover, in another western blot experiment, treatment with hydroxamic acid 6 led to upregulation of H3 acK9 and α-Tubulin acK40 levels, ascertaining its inhibitory activity toward both the class I HDACs and Class II B HDACs. The results of other assays were also encouraging as treatment with compound 6 led to the suppression of the colony formation ability of A549 cells, induction of apoptosis, and increase in autophagic flux. In silico studies led us to rationalize the results of the experimental assay, and some key interactions of compound 6 with the amino acid residues of HDAC isoforms were identified. In light of the impressive activity spectrum of compound 6, a pH-responsive nanocarrier (hyaluronic acid-compound 6 nanoparticles) was prepared. The dialysis bag approach was used for the assessment of the nanoparticles under both normal and acidic circumstances, and the pH-sensitive nature of hyaluronic acid-compound 6 nanoparticles was confirmed. Delightfully, the nanoformulation was devoid of cytotoxicity against the L929 mouse fibroblast cells (normal settings) and exhibited selective cytotoxicity towards the A549 lung cancer cell lines. In a nutshell, compound 6 appears to be a promising adduct, and a detailed investigation of this compound might yield a therapeutic for the treatment of lung cancer.

Keywords: HDAC inhibitors, lung cancer, scaffold, hyaluronic acid, nanoparticles

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Authors: Kirsten Techmer, Jan-Erik Rybak, Simon Rudolph

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Natural formed pyrites (FeS2) are frequent sulfides in sedimentary and metamorphic rocks. Growth textures of idiomorphic pyrite assemblages reflect the conditions during their formation in the geologic sequence, furtheron the local texture analyses of the growth patterns of pyrite assemblages by EBSD reveal the possibility to resolve the growth conditions during the formation of pyrite at the micron scale. The spatial resolution of local texture measurements in the Scanning Electron Microscope used can be in the nanomete scale. Orientation contrasts resulting from domains of smaller misorientations within larger pyrite crystals can be resolved as well. The electron optical studies have been carried out in a Field-Emission Scanning Electron Microscope (FEI Quanta 200) equipped with a CCD camera to study the orientation contrasts along the surfaces of pyrite. Idiomorphic cubic single crystals of pyrite, polycrystalline assemblages of pyrite, spherically grown spheres of pyrite as well as pyrite-bearing ammonites have been studied by EBSD in the Scanning Electron Microscope. Samples were chosen to show no or minor secondary deformation and an idiomorphic 3D crystal habit, so the local textures of pyrite result mainly from growth and minor from deformation. The samples studied derived from Navajun (Spain), Chalchidiki (Greece), Thüringen (Germany) and Unterkliem (Austria). Chemical analyses by EDAX show pyrite with minor inhomogeneities e.g., single crystals of galena and chalcopyrite along the grain boundaries of larger pyrite crystals. Intergrowth between marcasite and pyrite can be detected in one sample. Pyrite may form intense growth twinning lamellae on {011}. Twinning, e.g., contact twinning is abundant within the crystals studied and the individual twinning lamellaes can be resolved by EBSD. The ammonites studied show a replacement of the shale by newly formed pyrite resulting in an intense intergrowth of calcite and pyrite. EBSD measurements indicate a polycrystalline microfabric of both minerals, still reflecting primary surface structures of the ammonites e.g, the Septen. Discs of pyrite (“pyrite dollar”) as well as pyrite framboids show growth patterns comprising a typical microfabric. EBSD studies reveal an equigranular matrix in the inner part of the discs of pyrite and a fiber growth with larger misorientations in the outer regions between the individual segments. This typical microfabric derived from a formation of pyrite crystals starting at a higher nucleation rate and followed by directional crystal growth. EBSD studies show, that the growth texture of pyrite in the samples studied reveals a correlation between nucleation rate and following growth rate of the pyrites, thus leading to the characteristic crystal habits. Preferential directional growth at lower nucleation rates may lead to the formation of 3D framboids of pyrite. Crystallographic misorientations between the individual fibers are similar. In ammonites studied, primary anisotropies of the substrates like e.g., ammonitic sutures, influence the nucleation, crystal growth and habit of the newly formed pyrites along the surfaces.

Keywords: Electron Back Scatter Diffraction (EBSD), growth pattern, Fe-sulfides (pyrite), texture analyses

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Authors: Komal K., Cleary F., Wells J S.G., Bennett L

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Smart fabric garments enable various monitoring applications across sectors such as healthcare, sports and fitness, and the military. Healthcare smart garments monitoring EEG, EMG, and ECG rely on the use of electrodes (dry or wet). However, such electrodes, when used for long-term monitoring, can cause discomfort and skin irritation for the wearer because of their inflexible structure and weight. Ongoing research has been investigating textile-based electrodes (textrodes) in order to provide more comfortable and usable fabric-based electrodes capable of providing intuitive biopotential monitoring. Progress has been made in this space, but they still face a critical design challenge in maintaining consistent skin contact, which directly impacts signal quality. Furthermore, there is a lack of an ISO-based testing framework to validate the electrode design and assess its ability to achieve enhanced performance, strength, usability, and durability. This study proposes the development and evaluation of an ISO-compliant testing framework for standard 2D and advanced 3D embroidered textrodes designs that have a unique structure in order to establish enhanced skin contact for the wearer. This testing framework leverages ISO standards: ISO 13934-1:2013 for tensile and zone-wise strength tests; ISO 13937-2 for tear tests; and ISO 6330 for washing, validating the textrode's performance, a necessity for wearables health parameter monitoring applications. Five textrodes (C1-C5) were designed using EPC win digitization software. Varying patterns such as running stitches, lock stitches, back-to-back stitches, and moss stitches were used to create various embroidered tetrodes samples using Madeira HC12 conductive thread with a resistivity of 100 ohm/m. The textrode designs were then fabricated using a ZSK technical embroidery machine. A comparative analysis was conducted based on a series of laboratory tests adhering to ISO compliance requirements. Tests focusing on the application of strain were applied to the textrodes, and these included: (1) analysis of the electrode's overall surface area strength; (2) assessment of the robustness of the textrodes boundaries; and (3) the assignment of fault test zones to each textrode, where vertical and horizontal slits of 3mm were applied to evaluate the performance of textrodes and its durability. Specific ISO-compliant tests linked to washing were conducted multiple times on each textrode sample to assess both mechanical and chemical damage. Additionally, abrasion and pilling tests were performed to evaluate mechanical damage on the surface of the textrodes and to compare it with the washing test. Finally, the textrodes were assessed based on morphological and surface resistance changes. Results demonstrate that textrode C4, featuring a 3-D layered structure consisting of foam, fabric, and conductive thread layers, significantly enhances skin-electrode contact for biopotential recording. The inclusion of a 3D foam layer was particularly effective in maintaining the shape of the electrode during strain tests, making it the top-performing textrode sample. Therefore, the layered 3D design structure of textrode C4 ranks highest when tested for durability, reusability, and washability. The ISO testing framework established in this study will support future research, validating the durability and reliability of textrodes for a wide range of applications.

Keywords: smart fabric, textrodes, testing framework, ISO compliant

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Authors: Raha Bahreini

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This paper discusses the roll-back of women’s sexual and reproductive rights in the Islamic Republic of Iran, which has come in the wake of a striking shift in the country’s official population policies. Since the late 1980s, Iran has won worldwide praise for its sexual and reproductive health and services, which have contributed to a steady decline in the country’s fertility rate–from 7.0 births per women in 1980 to 5.5 in 1988, 2.8 in 1996 and 1.85 in 2014. This is owed to a significant increase in the voluntary use of modern contraception in both rural and urban areas. In 1976, only 37 per cent of women were using at least one method of contraception; by 2014 this figure had reportedly risen to a high of nearly 79 per cent for married girls and women living in urban areas and 73.78 per cent for those living in rural areas. Such progress may soon be halted. In July 2012, Iran’s Supreme Leader Ayatollah Sayed Ali Khamenei denounced Iran’s family planning policies as an imitation of Western lifestyle. He exhorted the authorities to increase Iran’s population to 150 to 200 million (from around 78.5 million), including by cutting subsidies for contraceptive methods and dismantling the state’s Family and Population Planning Programme. Shortly thereafter, Iran’s Minister of Health and Medical Education announced the scrapping of the budget for the state-funded Family and Population Planning Programme. Iran’s Parliament subsequently introduced two bills; the Comprehensive Population and Exaltation of Family Bill (Bill 315), and the Bill to Increase Fertility Rates and Prevent Population Decline (Bill 446). Bill 446 outlaws voluntary tubectomies, which are believed to be the second most common method of modern contraception in Iran, and blocks access to information about contraception, denying women the opportunity to make informed decisions about the number and spacing of their children. Coupled with the elimination of state funding for Iran’s Family and Population Programme, the move would undoubtedly result in greater numbers of unwanted pregnancies, forcing more women to seek illegal and unsafe abortions. Bill 315 proposes various discriminatory measures in the areas of employment, divorce, and protection from domestic violence in order to promote a culture wherein wifedom and child-bearing is seen as women’s primary duty. The Bill, for example, instructs private and public entities to prioritize, in sequence, men with children, married men without children and married women with children when hiring for certain jobs. It also bans the recruitment of single individuals as family law lawyers, public and private school teachers and members of the academic boards of universities and higher education institutes. The paper discusses the consequences of these initiatives which would, if continued, set the human rights of women and girls in Iran back by decades, leaving them with a future shaped by increased inequality, discrimination, poor health, limited choices and restricted freedoms, in breach of Iran’s international human rights obligations.

Keywords: family planning and reproductive health, gender equality and empowerment of women, human rights, population growth

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Authors: Mohammad H. Yarmohammadian, Fatemeh Rezaei

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Introduction: Improving patient safety in health systems is one of the main priorities in healthcare systems, so clinical risk management in organizations has become increasingly significant. Although several tools have been developed for clinical risk management, each has its own limitations. Aims: This study aims to develop a comprehensive tool that can complete the limitations of each risk assessment and management tools with the advantage of other tools. Methods: Procedure was determined in two main stages included development of an initial model during meetings with the professors and literature review, then implementation and verification of final model. Subjects and Methods: This study is a quantitative − qualitative research. In terms of qualitative dimension, method of focus groups with inductive approach is used. To evaluate the results of the qualitative study, quantitative assessment of the two parts of the fourth phase and seven phases of the research was conducted. Purposive and stratification sampling of various responsible teams for the selected process was conducted in the operating room. Final model verified in eight phases through application of activity breakdown structure, failure mode and effects analysis (FMEA), healthcare risk priority number (RPN), root cause analysis (RCA), FT, and Eindhoven Classification model (ECM) tools. This model has been conducted typically on patients admitted in a day-clinic ward of a public hospital for surgery in October 2012 to June. Statistical Analysis Used: Qualitative data analysis was done through content analysis and quantitative analysis done through checklist and edited RPN tables. Results: After verification the final model in eight-step, patient's admission process for surgery was developed by focus discussion group (FDG) members in five main phases. Then with adopted methodology of FMEA, 85 failure modes along with its causes, effects, and preventive capabilities was set in the tables. Developed tables to calculate RPN index contain three criteria for severity, two criteria for probability, and two criteria for preventability. Tree failure modes were above determined significant risk limitation (RPN > 250). After a 3-month period, patient's misidentification incidents were the most frequent reported events. Each RPN criterion of misidentification events compared and found that various RPN number for tree misidentification reported events could be determine against predicted score in previous phase. Identified root causes through fault tree categorized with ECM. Wrong side surgery event was selected by focus discussion group to purpose improvement action. The most important causes were lack of planning for number and priority of surgical procedures. After prioritization of the suggested interventions, computerized registration system in health information system (HIS) was adopted to prepare the action plan in the final phase. Conclusion: Complexity of health care industry requires risk managers to have a multifaceted vision. Therefore, applying only one of retrospective or prospective tools for risk management does not work and each organization must provide conditions for potential application of these methods in its organization. The results of this study showed that the integrated clinical risk management model can be used in hospitals as an efficient tool in order to improve clinical governance.

Keywords: failure modes and effective analysis, risk management, root cause analysis, model

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Authors: Irakli Javakhishvili, Tamara Tsutsunava, Giorgi Beridze

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The Caucasus is a component of the Mediterranean collision belt. The Dizi series is situated within the Greater Caucasian region of the Caucasus and crops out in the core of the Svaneti anticlinorium. The series was formed in the continental slope conditions on the southern passive margin of the small ocean basin. The Dizi series crops out on about 560 square km with the thickness 2000-2200 m. The rocks are faunally dated from the Devonian to the Triassic inclusive. The series is composed of terrigenous phyllitic schists, sandstones, quartzite aleurolites and lenses and interlayers of marbleized limestones. During the early Cimmerian orogeny, they underwent regional metamorphism of chlorite-sericite subfacies of greenschist facies. Typical minerals of metapelites are chlorite, sericite, augite, quartz, and tourmaline, but of basic rocks - actinolite, fibrolite, prehnite, calcite, and chlorite are developed. Into the Dizi series, polyphase intrusions of gabbros, diorites, quartz-diorites, syenite-diorites, syenites, and granitoids are intruded. Their K-Ar age dating (176-165Ma) points out that their formation corresponds to the Bathonian orogeny. The Dizi series is well-studied geologically, but very complicated processes of its regional and contact metamorphisms are insufficiently investigated. The aim of the authors was a detailed study of contact metamorphism processes of the series rocks. Investigations were accomplished applying the following methodologies: finding of key sections, a collection of material, microscopic study of samples, microprobe and structural analysis of minerals and X-ray determination of elements. The Dizi series rocks formed under the influence of the Bathonian magmatites on metapelites and carbonate-enriched rocks. They are represented by quartz, biotite, sericite, graphite, andalusite, muscovite, plagioclase, corundum, cordierite, clinopyroxene, hornblende, cummingtonite, actinolite, and tremolite bearing hornfels, marbles, and skarns. The contact metamorphism aureole reaches 350 meters. Biotite is developed only in contact-metamorphosed rocks and is a rather informative index mineral. In metapelites, biotite is formed as a result of the reaction between phengite, chlorite, and leucoxene, but in basites, it replaces actinolite or actinolite-hornblende. To study the compositional regularities of biotites, they were investigated from both - metapelites and metabasites. In total, biotite from the basites is characterized by an increased of titanium in contrast to biotite from metapelites. Biotites from metapelites are distinguished by an increased amount of aluminum. In biotites an increased amount of titanium and aluminum is observed as they approximate the contact, while their magnesia content decreases. Metapelite biotites are characterized by an increased amount of alumina in aluminum octahedrals, in contrast to biotite of the basites. In biotites of metapelites, the amount of tetrahedric aluminum is 28–34%, octahedral - 15–26%, and in basites tetrahedral aluminum is 28–33%, and octahedral 7–21%. As a result of the study of minerals, including biotite, from the contact-metamorphosed rocks of the Dizi series three exocontact zones with corresponding mineral assemblages were identified. It was established that contact metamorphism in the aureole of the Dizi series intrusions is going on at a significantly higher temperature and lower pressure than the regional metamorphism preceding the contact metamorphism.

Keywords: biotite, contact metamorphism, Dizi series, the Greater Caucasus

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Authors: Milica B. Veljković, Milica B. Simović, Marija M. Ćorović, Ana D. Milivojević, Anja I. Petrov, Katarina M. Banjanac, Dejan I. Bezbradica

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In recent decades, the scientific community has recognized the growing importance of prebiotics, and therefore, numerous studies are focused on their economic production due to their low presence in natural resources. It has been confirmed that prebiotics is a source of energy for probiotics in the gastrointestinal tract (GIT) and enable their proliferation, consequently leading to the normal functioning of the intestinal microbiota. Also, products of their fermentation are short-chain fatty acids (SCFA), which play a key role in maintaining and improving the health not only of the GIT but also of the whole organism. Among several confirmed prebiotics, fructooligosaccharides (FOS) are considered interesting candidates for use in a wide range of products in the food industry. They are characterized as low-calorie and non-cariogenic substances that represent an adequate sugar substitute and can be considered suitable for use in products intended for diabetics. The subject of this research will be the production of FOS by transforming sucrose using a fructosyltransferase (FTase) present in commercial preparation Pectinex® Ultra SP-L, with special emphasis on the development of adequate FTase immobilization method that would enable selective isolation of the enzyme responsible for the synthesis of FOS from the complex enzymatic mixture. This would lead to considerable enzyme purification and allow its direct incorporation into different sucrose-based products without the fear that the action of the other hydrolytic enzymes may adversely affect the products' functional characteristics. Accordingly, the possibility of selective immobilization of the enzyme using support with primary amino groups, Purolite® A109, which was previously activated and modified using glutaraldehyde (GA), was investigated. In the initial phase of the research, the effects of individual immobilization parameters such as pH, enzyme concentration, and immobilization time were investigated to optimize the process using support chemically activated with 15% and 0.5% GA to form dimers and monomers, respectively. It was determined that highly active immobilized preparations (371.8 IU/g of support - dimer and 213.8 IU/g of support – monomer) were achieved under acidic conditions (pH 4) provided that an enzyme concentration was 50 mg/g of support after 7 h and 3 h, respectively. Bearing in mind the obtained results of the expressed activity, it is noticeable that the formation of dimers showed higher reactivity compared to the form of monomers. Also, in the case of support modification using 15% GA, the value of the ratio of FTase and pectinase (as dominant enzyme mixture component) activity immobilization yields was 16.45, indicating the high feasibility of selective immobilization of FTase on modified polystyrene resin. After obtaining immobilized preparations of satisfactory features, they were tested in a reaction of FOS synthesis under determined optimal conditions. The maximum FOS yields of approximately 50% of total carbohydrates in the reaction mixture were recorded after 21 h. Finally, it can be concluded that the examined immobilization method yielded highly active, stable and, more importantly, refined enzyme preparation that can be further utilized on a larger scale for the development of continual processes for FOS synthesis, as well as for modification of different sucrose-based mediums.

Keywords: chemical modification, fructooligosaccharides, glutaraldehyde, immobilization of fructosyltransferase

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Authors: Chung Yan Natalia Yeung, Man Kit Indy Ho, Kin Yu Stan Chan, Ho Pui Kipper Lam, Man Wah Genie Tong, Tze Chung Jim Luk

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Excessive foot pronation is a well-known risk factor of knee and foot injuries such as patellofemoral pain, patellar and Achilles tendinopathy, and plantar fasciitis. Low-Dye taping (LDT) application is not uncommon for basketball players to control excessive foot pronation for pain control and injury prevention. The primary potential benefits of using LDT include providing additional supports to medial longitudinal arch and restricting the excessive midfoot and subtalar motion in weight-bearing activities such as running and landing. Meanwhile, restrictions provided by the rigid tape may also potentially limit functional joint movements and sports performance. Coaches and athletes need to weigh the potential benefits and harmful effects before making a decision if applying LDT technique is worthwhile or not. However, the influence of using LDT on basketball-related performance such as explosive and reactive strength is not well understood. Therefore, the purpose of this study was to investigate the change of drop jump (DJ) and countermovement jump (CMJ) performance before and after LDT application for collegiate male basketball players. In this within-subject crossover study, 12 healthy male basketball players (age: 21.7 ± 2.5 years) with at least 3-year regular basketball training experience were recruited. Navicular drop (ND) test was adopted as the screening and only those with excessive pronation (ND ≥ 10mm) were included. Participants with recent lower limb injury history were excluded. Recruited subjects were required to perform both ND, DJ (on a platform of 40cm height) and CMJ (without arms swing) tests in series during taped and non-taped conditions in the counterbalanced order. Reactive strength index (RSI) was calculated by using the flight time divided by the ground contact time measured. For DJ and CMJ tests, the best of three trials was used for analysis. The difference between taped and non-taped conditions for each test was further calculated through standardized effect ± 90% confidence intervals (CI) with clinical magnitude-based inference (MBI). Paired samples T-test showed significant decrease in ND (-4.68 ± 1.44mm; 95% CI: -3.77, -5.60; p < 0.05) while MBI demonstrated most likely beneficial and large effect (standardize effect: -1.59 ± 0.27) in LDT condition. For DJ test, significant increase in both flight time (25.25 ± 29.96ms; 95% CI: 6.22, 44.28; p < 0.05) and RSI (0.22 ± 0.22; 95% CI: 0.08, 0.36; p < 0.05) were observed. In taped condition, MBI showed very likely beneficial and moderate effect (standardized effect: 0.77 ± 0.49) in flight time, possibly beneficial and small effect (standardized effect: -0.26 ± 0.29) in ground contact time and very likely beneficial and moderate effect (standardized effect: 0.77 ± 0.42) in RSI. No significant difference in CMJ was observed (95% CI: -2.73, 2.08; p > 0.05). For basketball players with pes planus, applying LDT could substantially support the foot by elevating the navicular height and potentially provide acute beneficial effects in reactive strength performance. Meanwhile, no significant harmful effect on CMJ was observed. Basketball players may consider applying LDT before the game or training to enhance the reactive strength performance. However since the observed effects in this study could not generalize to other players without excessive foot pronation, further studies on players with normal foot arch or navicular height are recommended.

Keywords: flight time, pes planus, pronated foot, reactive strength index

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Authors: Pedro Felgueiras, Ana Miguel, Nélson Almeida, Raquel Silva

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Objective: Through the study of a clinical case of delusional somatic disorder secondary to phantogeusia, we aim to highlight the importance of considering psychosomatic conditions in differential diagnosis, as well as to emphasize the complexity of its comprehension, treatment, and respective impact on patients’ functioning. Methods: Bearing this in mind, we conducted a critical analysis of a case series based on patient observations, clinical data, and complementary diagnostic methods, as well as a non-systematic review of the literature on the subject. Results: A 61-year-old female patient with no history of psychiatric conditions. Family psychiatric history of mood disorder (depression), with psychotic features found in her mother. Medical history of many comorbidities affecting different organ systems (endocrine, gastrointestinal, genitourinary, ophthalmological). Documented neuroticism traits of personality. The patient’s family described a persistent concern about several physical symptoms across her life, with a continuous effort to obtain explanations about any sensation out of her normal perception. Since being subjected to endoscopy in 2018, she started complaints of persistent phantogeusia (acid taste) and developed excessive thoughts, feelings, and behaviors associated with this somatic symptom. The patient was evaluated by several medical specialties, and an extensive panel of medical exams was carried out, excluding any disease. Besides all the investigation and with no evidence of disease signs, acute anxiety, time, and energy dispended to this symptom culminated in severe psychosocial impairment. The patient was admitted to a psychiatric ward for investigation and treatment of this clinical picture, leading to the diagnosis of the delusional somatic disorder. In order to exclude the acute organic etiology of this psychotic disorder, an analytic panel was carried out with no abnormal results. In the context of a psychotic clinical picture, a CT scan was performed, which revealed a right cortical vascular lesion. Neuropsychological evaluation was made, with the description of cognitive functioning being globally normative. During treatment with an antipsychotic (pimozide), a complete remission of the somatic delusion was associated with the disappearance of gustative perception disturbance. In follow-up, a relapse of gustative sensation was documented, and her thoughts and speech were dominated by concerns about multiple somatic symptoms. Conclusion: In terms of abnormal bodily sensations, the oral cavity is one of the frequent sites of delusional disorder. Patients with these gustatory perception distortions complain about unusual sensations without corresponding abnormal findings in the oral area. Its pathophysiology has not been fully elucidated yet. In terms of its comprehensive psychopathology, this case was hypothesized as a paranoid development of a delusional somatic disorder triggered by a post-invasive procedure phantogeusia (which is described as a possible side effect of an endoscopy) in a patient with an anankastic personality. This case presents interesting psychopathology, reinforcing the complexity of psychosomatic disorders in terms of their etiopathogenesis, clinical treatment, and long-term prognosis.

Keywords: psychosomatics, delusional somatic disorder, phantogeusia, paranoid development

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Authors: Maryam Mohammad Hadi, Heather Nesbitt, Hamzah Masood, Hashim Ahmed, Mark Emberton, John Callan, Alexander MacRobert, Anthony McHale, Nikolitsa Nomikou

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Sonodynamic therapy (SDT) utilises ultrasound in combination with sensitizers, such as porphyrins, for the production of cytotoxic reactive oxygen species (ROS) and the confined ablation of tumours. Ultrasound can be applied locally, and the acoustic waves, at frequencies between 0.5-2 MHz, are transmitted efficiently through tissue. SDT does not require highly toxic agents, and the cytotoxic effect only occurs upon ultrasound exposure at the site of the lesion. Therefore, this approach is not associated with adverse side effects. Further highlighting the benefits of SDT, no cancer cell population has shown resistance to therapy-triggered ROS production or their cytotoxic effects. This is particularly important, given the as yet unresolved issues of radiation and chemo-resistance, to the authors’ best knowledge. Another potential future benefit of this approach – considering its non-thermal mechanism of action – is its possible role as an adjuvant to immunotherapy. Substantial pre-clinical studies have demonstrated the efficacy and targeting capability of this therapeutic approach. However, SDT has yet to be fully characterised and appropriately exploited for the treatment of cancer. In this study, a formulation based on multistimulus-responsive sensitizer-containing nanoparticles that can accumulate in advanced prostate tumours and increase the therapeutic efficacy of SDT has been developed. The formulation is based on a polyglutamate-tyrosine (PGATyr) co-polymer carrying hematoporphyrin. The efficacy of SDT in this study was demonstrated using prostate cancer as the translational exemplar. The formulation was designed to respond to the microenvironment of advanced prostate tumours, such as the overexpression of the proteolytic enzymes, cathepsin-B and prostate-specific membrane antigen (PSMA), that can degrade the nanoparticles, reduce their size, improving both diffusions throughout the tumour mass and cellular uptake. The therapeutic modality was initially tested in vitro using LNCaP and PC3 cells as target cell lines. The SDT efficacy was also examined in vivo, using male SCID mice bearing LNCaP subcutaneous tumours. We have demonstrated that the PGATyr co-polymer is digested by cathepsin B and that digestion of the formulation by cathepsin-B, at tumour-mimicking conditions (acidic pH), leads to decreased nanoparticle size and subsequent increased cellular uptake. Sonodynamic treatment, at both normoxic and hypoxic conditions, demonstrated ultrasound-induced cytotoxic effects only for the nanoparticle-treated prostate cancer cells, while the toxicity of the formulation in the absence of ultrasound was minimal. Our in vivo studies in immunodeficient mice, using the hematoporphyrin-containing PGATyr nanoparticles for SDT, showed a 50% decrease in LNCaP tumour volumes within 24h, following IV administration of a single dose. No adverse effects were recorded, and body weight was stable. The results described in this study clearly demonstrate the promise of SDT to revolutionize cancer treatment. It emphasizes the potential of this therapeutic modality as a fist line treatment or in combination treatment for the elimination or downstaging of difficult to treat cancers, such as prostate, pancreatic, and advanced colorectal cancer.

Keywords: sonodynamic therapy, nanoparticles, tumour ablation, ultrasound

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Authors: Shlomit Paz, Meir Broza

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Cholera is an acute intestinal infection caused by ingestion of food or water contaminated with the bacterium Vibrio cholerae. It has a short incubation period and produces an enterotoxin that causes copious, painless, watery diarrhoea that can quickly lead to severe dehydration and death if treatment is not promptly given. In an epidemic, the source of the contamination is usually the feces of an infected person. The disease can spread rapidly in areas with poor treatment of sewage and drinking water. Cholera remains a global threat and is one of the key indicators of social development. An estimated 3-5 million cases and over 100,000 deaths occur each year around the world. The relevance of climatic events as causative factors for cholera epidemics is well known. However, the examination of the involvement of winds in intra-continental disease distribution is new. The study explore the hypothesis that the spreading of cholera epidemics may be related to the dominant wind direction over land by presenting the influence of the wind direction on windborn dissemination by flying insects, which may serve as vectors. Chironomids ("non-biting midges“) exist in the majority of freshwater aquatic habitats, especially in estuarine and organic-rich water bodies typical to Vibrio cholerae. Chironomid adults emerge into the air for mating and dispersion. They are highly mobile, huge in number and found frequently in the air at various elevations. The huge number of chironomid egg masses attached to hard substrate on the water surface, serve as a reservoir for the free-living Vibrio bacteria. Both male and female, while emerging from the water, may carry the cholera bacteria. In experimental simulation, it was demonstrated that the cholera-bearing adult midges are carried by the wind, and transmit the bacteria from one body of water to another. In our previous study, the geographic diffusions of three cholera outbreaks were examined through their linkage with the wind direction: a) the progress of Vibrio cholerae O1 biotype El Tor in Africa during 1970–1971 and b) again in 2005–2006; and c) the rapid spread of Vibrio cholerae O139 over India during 1992–1993. Using data and map of cholera dissemination (WHO database) and mean monthly SLP and geopotential data (NOAA NCEP-NCAR database), analysis of air pressure data at sea level and at several altitudes over Africa, India and Bangladesh show a correspondence between the dominant wind direction and the intra-continental spread of cholera. The results support the hypothesis that aeroplankton (the tiny life forms that float in the air and that may be caught and carried upward by the wind, landing far from their origin) carry the cholera bacteria from one body of water to an adjacent one. In addition to these findings, the current follow-up study will present new results regarding the possible involvement of winds in the spreading of cholera in recent outbreaks (2010-2013). The findings may improve the understanding of how climatic factors are involved in the rapid distribution of new strains throughout a vast continental area. Awareness of the aerial transfer of Vibrio cholerae may assist health authorities by improving the prediction of the disease’s geographic dissemination.

Keywords: cholera, Vibrio cholerae, wind direction, Vibrio cholerae dissemination

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Authors: Sami El Khatib, Agnès Leroux, Jean-Louis Merlin, François Guillemin, Marie-Ange D’Hallewin

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Photodynamic therapy (PDT) is a treatment modality based on the cytotoxic effect occurring on the target tissues by interaction of a photosensitizer with light in the presence of oxygen. One of the major advances in PDT can be attributed to the use of topical aminolevulinic (ALA) to induce Protoporphyrin IX (PpIX) for the treatment of early stage cancers as well as diagnosis. ALA is a precursor of the heme synthesis pathway. Locally delivered to the target tissue ALA overcomes the negative feedback exerted by heme and promotes the transient formation of PpIX in situ to reach critical effective levels in cells and tissue. Whereas early steps of the heme pathway occur in the cytosol, PpIX synthesis is shown to be held in the mitochondrial membranes and PpIX fluorescence is expected to accumulate in close vicinity of the initial building site and to progressively diffuse to the neighboring cytoplasmic compartment or other lipophylic organelles. PpIX is known to be highly reactive and will be degraded when irradiated with light. PpIX photobleaching is believed to be governed by a singlet oxygen mediated mechanism in the presence of oxidized amino acids and proteins. PpIX photobleaching and subsequent spectral phototransformation were described widely in tumor cells incubated in vitro with ALA solution, or ex vivo in human and porcine mucosa superfused with hexylaminolevulinate (hALA). PpIX photobleaching was also studied in vivo, using animal models such as normal or tumor mice skin and orthotopic rat bladder model. Hexyl aminolevulinate a more potent lipophilic derivative of ALA was proposed as an adjunct to standard cystoscopy in the fluorescence diagnosis of bladder cancer and other malignancies. We have previously reported the effectiveness of hALA mediated PDT of rat bladder cancer. Although normal and tumor bladder epithelium exhibit similar fluorescence intensities after intravesical instillation of two hALA concentrations (8 and 16 mM), the therapeutic response at 8mM and 20J/cm2 was completely different from the one observed at 16mM irradiated with the same light dose. Where the tumor is destroyed, leaving the underlying submucosa and muscle intact after an 8 mM instillation, 16mM sensitization and subsequent illumination results in the complete destruction of the underlying bladder wall but leaves the tumor undamaged. The object of the current study is to try to unravel the underlying mechanism for this apparent contradiction. PpIX extraction showed identical amounts of photosensitizer in tumor bearing bladders at both concentrations. Photobleaching experiments revealed mono-exponential decay curves in both situations but with a two times faster decay constant in case of 16mM bladders. Fluorescence microscopy shows an identical fluorescence pattern for normal bladders at both concentrations and tumor bladders at 8mM with bright spots. Tumor bladders at 16 mM exhibit a more diffuse cytoplasmic fluorescence distribution. The different response to PDT with regard to the initial pro-drug concentration can thus be attributed to the different cellular localization.

Keywords: bladder cancer, hexyl-aminolevulinate, photobleaching, confocal fluorescence microscopy

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Authors: Abouchouaib Belahmira, Joerg W. Schneider, Hafid Saber, Sara Akboub

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The lithofacies analyzed herein were reported from the interbedded fluvial and lacustrine deposits of the Oued Issene and El Menizla formations. These formations are part of the sedimentary fill of the Carboniferous (Stephanian) submontaneous Souss basin. The latter is situated in the western High Atlas Mountains, south-central Morocco, about 50km east of Agadir. The Souss basin started as a single basin but was separated into sub-basins called Ida Ou Zal and Ida Ou Ziki by sinistral displacement along the west branch of the Tizi N'Test Fault during the end of the Mauritanid phase of the Variscan orogeny in Morocco, after the early Stephanian (Kasimovian) and before the late middle Permian (Capitanian). The studied succession is a monotonous finning-upward sequence of 1800 m thick. It consists of fine-grained sandstone, finely bedded siltstone and thinly laminated claystone, and black shale. Herein we provide a detailed characterization of lithofacies of the upper El Menizla and Oued Issène formations, with a focus on the prevailing overbank to flood plain fine-grained lithofacies. The studied facies are capping the Stephanian alluvial fan basal clast-supported conglomerates that are intercalated bedded coarse-grained sandstones of Ikhourba Formation in the Ou Zal subbasin and Tajgaline Formation in the Ida Ou Ziki subbasin, respectively. Within the fluvial elements, only two main facies have been observed. It comprises channel-fill and channel-bar deposits, mostly occur as lenticular –shape sand bodies or sheet-like sand greenish to gray fine-to medium (Fm), massive internally structureless, or very locally exhibits a medium to large scale trough-cross bedding medium to coarse sandstone (St), observable in relatively thicker bed. These facies are laterally extensive, with a thickness varying from a few to several meters. Finer-grained sediments such as mud can be present as drapes over bedforms. Whilst the fluvial association FA1, the overbank elements are represented by a relatively wide range of 5 facies. This exhibit mostly a cm scale horizontally bedded greenish fine- to medium sand and silt, and mm scale fossiliferous thinly laminated dark gray- black Corganic-rich clays to siltstone associated with black shale. Thus, FA2 includes flood plain fines (Fh, R) associated with the paleosols and back swamp coaly clay facies (C). The floodplain lake element comprises only laminated organic-rich dark gray facies of claystone, black shale, and graded siltstone. Bedsets are dm to several meters thick (typically < 1 m thick). They are intercalated between several m-thick fluvial sandstone, extend over a few meters, and are poorly bioturbated. The lacustrine facies described in this study have been divided into two sub-facies (Fl, B) based on field observations that indicate differing environmental conditions of formation. Thus, the thorough analysis of the lithofacies of the Souss basin units allows us to reconstruct the original environment that was interpreted as a typical fluvial-dominated braided to anastomosing wide distributary channel system and surrounding deep to shallow freshwater floodplain lakes and back swamps.

Keywords: Souss, carboniferous, facies, depositional setting

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Authors: A. Casale, J. Alessi, C. N. Bianchi, G. Bozzini, M. Brunoldi, V. Cappanera, P. Corvisiero, G. Fanciulli, D. Grosso, N. Magnoli, A. Mandich, C. Melchiorre, C. Morri, P. Povero, N. Stasi, M. Taiuti, G. Viano, M. Wurtz

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This work describes a real-time algorithm for detecting, tracking and classifying single motorboats, developed using the acoustic data recorded by a hydrophone array within the framework of EU LIFE + project ARION (LIFE09NAT/IT/000190). The project aims to improve the conservation status of bottlenose dolphins through a real-time simultaneous monitoring of their population and surface ship traffic. A Passive Acoustic Monitoring (PAM) system is installed on two autonomous permanent marine buoys, located close to the boundaries of the Marine Protected Area (MPA) of Portofino (Ligurian Sea- Italy). Detecting surface ships is also a necessity in many other sensible areas, such as wind farms, oil platforms, and harbours. A PAM system could be an effective alternative to the usual monitoring systems, as radar or active sonar, for localizing unauthorized ship presence or illegal activities, with the advantage of not revealing its presence. Each ARION buoy consists of a particular type of structure, named meda elastica (elastic beacon) composed of a main pole, about 30-meter length, emerging for 7 meters, anchored to a mooring of 30 tons at 90 m depth by an anti-twist steel wire. Each buoy is equipped with a floating element and a hydrophone tetrahedron array, whose raw data are send via a Wi-Fi bridge to a ground station where real-time analysis is performed. Bottlenose dolphin detection algorithm and ship monitoring algorithm are operating in parallel and in real time. Three modules were developed and commissioned for ship monitoring. The first is the detection algorithm, based on Time Difference Of Arrival (TDOA) measurements, i.e., the evaluation of angular direction of the target respect to each buoy and the triangulation for obtaining the target position. The second is the tracking algorithm, based on a Kalman filter, i.e., the estimate of the real course and speed of the target through a predictor filter. At last, the classification algorithm is based on the DEMON method, i.e., the extraction of the acoustic signature of single vessels. The following results were obtained; the detection algorithm succeeded in evaluating the bearing angle with respect to each buoy and the position of the target, with an uncertainty of 2 degrees and a maximum range of 2.5 km. The tracking algorithm succeeded in reconstructing the real vessel courses and estimating the speed with an accuracy of 20% respect to the Automatic Identification System (AIS) signals. The classification algorithm succeeded in isolating the acoustic signature of single vessels, demonstrating its temporal stability and the consistency of both buoys results. As reference, the results were compared with the Hilbert transform of single channel signals. The algorithm for tracking multiple targets is ready to be developed, thanks to the modularity of the single ship algorithm: the classification module will enumerate and identify all targets present in the study area; for each of them, the detection module and the tracking module will be applied to monitor their course.

Keywords: acoustic-noise, bottlenose-dolphin, hydrophone, motorboat

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Authors: Tugba Altin

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In an era where the impacts of climate change resonate more pronouncedly than ever, communities globally grapple with events bearing both tangible and intangible ramifications. Situating this within the evolving landscapes of Psychological and Behavioral Sciences, this research probes the profound psychological and behavioral responses evoked by such events. The Lytton Creek Fire of 2021 epitomizes these challenges. While tangible destruction is immediate and evident, the intangible repercussions—emotional distress, disintegration of cultural landscapes, and disruptions in place attachment (PA)—require meticulous exploration. PA, emblematic of the emotional and cognitive affiliations individuals nurture with their environments, emerges as a cornerstone for comprehending how environmental cataclysms influence cultural identity and bonds to land. This study, harmonizing the core tenets of an interpretive phenomenological approach with a hermeneutic framework, underscores the pivotal nature of this attachment. It delves deep into the realm of individuals' experiences post the Lytton Creek Fire, unraveling the intricate dynamics of PA amidst such calamity. The study's methodology deviates from conventional paradigms. Instead of traditional interview techniques, it employs walking audio sessions and photo elicitation methods, granting participants the agency to immerse, re-experience, and vocalize their sentiments in real-time. Such techniques shed light on spatial narratives post-trauma and capture the otherwise elusive emotional nuances, offering a visually rich representation of place-based experiences. Central to this research is the voice of the affected populace, whose lived experiences and testimonies form the nucleus of the inquiry. As they renegotiate their bonds with transformed environments, their narratives reveal the indispensable role of cultural landscapes in forging place-based identities. Such revelations accentuate the necessity of integrating both tangible and intangible trauma facets into community recovery strategies, ensuring they resonate more profoundly with affected individuals. Bridging the domains of environmental psychology and behavioral sciences, this research accentuates the intertwined nature of tangible restoration with the imperative of emotional and cultural recuperation post-environmental disasters. It advocates for adaptation initiatives that are rooted in the lived realities of the affected, emphasizing a holistic approach that recognizes the profundity of human connections to landscapes. This research advocates the interdisciplinary exchange of ideas and strategies in addressing post-disaster community recovery strategies. It not only enriches the climate change discourse by emphasizing the human facets of disasters but also reiterates the significance of an interdisciplinary approach, encompassing psychological and behavioral nuances, for fostering a comprehensive understanding of climate-induced traumas. Such a perspective is indispensable for shaping more informed, empathetic, and effective adaptation strategies.

Keywords: place attachment, community recovery, disaster response, restorative landscapes, sensory response, visual methodologies

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Authors: Fouzia Arif, Arif S. Mohammad, Hifsa Altaf, Lubna Raees

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Introduction: The term "disability", refers to any condition that impedes the completion of daily tasks using traditional methods. In developing countries like Pakistan, disable population is usually excluded from the mainstream. In squatter settlements the situation is more critical. Sultanabad is one of the squatter settlements of Karachi. Purpose of case study is to improve the health of disabled children’s, and create awareness among the parents and community. Through a household visit, Shiraz, a young disabled boy of 15.5 years old was identified. Her mother articulated that her son was living normally and happily with his parents two years back. When he was 13 years old and student of class 8th, both his legs were traumatized in a Railway Train Accident while playing cricket. He got both femoral shaft fractured severely. He was taken to Jinnah Post Graduate Medical Centre (JPMC) where his left leg was amputated at above knee level and right leg was opened & fixed by reduction internally, luckily bone healed moderately with the passage of time. Methods: In Squatter settlements of Karachi Sultanabad, a survey was conducted in two sectors. Disability screening questionnaire was developed, collaboration with community through household visits, outreach sessions 23cases of disabled were identified who were socialized through sports, Musical program and get-together was organized with stockholder for creating awareness among community and parent’s. Collaboration was established with different NGOs, Government, stakeholders and community support for establishment of Physiotherapy Center. During home visit it was identified that Shiraz was on bed since last 1 year, his family could not afforded cost of physiotherapist and medical consultation due to poverty. Parents counseling was done mentioning that Shiraz needed to take treatment. After motivation his parents agreed for treatment. He was consulted by an orthopedic surgeon in AKUH, Who referred to DMC University of Health Science for rehabilitation service. There he was assessed and referred for Community Based Physiotherapy Centre Sultanabad. Physiotherapist visited home along with Coordinator for Special children and assessed him regularly, planned Physiotherapy treatment for abdominal, high muscles strutting exercise foot muscles strengthening exercise, knee mobilization weight bearing from partial to full weight gradually, also strengthen exercise were given for residual limb as the boy was dependent on it. He was also provided by an artificial leg and training was done. Result: Shiraz is now fully mobile, he can walk independently even out of home, functional ability progress improved and dependency factors reduced. It was difficult but not impossible. We all have sympathy but if we have empathy then we can rehabilitate the community in a better way. His parents are very happy and also the community is surprised to see him in such better condition. Conclusion: Combined efforts of physiotherapist, Coordinator of special children, community and parents made a drastic change in Shiraz’s case by continuously motivating him for better outcome. He is going to school regularly without support. Since he belongs to a poor family he faces financial constraints for education and clinical follow ups regularly.

Keywords: femoral shaft fracture, trauma, orthopedic surgeon, physiotherapy treatment

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Authors: E. Locatelli, I. Monaco, R. C. Martin, Y. Li, R. Pini, M. Chiariello, M. Comes Franchini

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Despite the many advantages of application of nanomaterials in the field of nanomedicine, increasing concerns have been expressed on their potential adverse effects on human health. There is urgency for novel green strategies toward novel materials with enhanced biocompatibility using safe reagents. Photothermal ablation therapy, which exploits localized heat increase of a few degrees to kill cancer cells, has appeared recently as a non-invasive and highly efficient therapy against various cancer types; anyway new agents able to generate hyperthermia when irradiated are needed and must have precise biocompatibility in order to avoid damage to healthy tissues and prevent toxicity. Recently, there has been increasing interest in magnesium as a biomaterial: it is the fourth most abundant cation in the human body, and it is essential for human metabolism. However magnesium nanoparticles (Mg NPs) have had limited diffusion due to the high reduction potential of magnesium cations, which makes NPs synthesis challenging. Herein, we report the synthesis of Mg NPs and their surface functionalization for the obtainment of a stable and biocompatible nanomaterial suitable for photothermal ablation therapy against cancer. We synthesized the Mg crystals by reducing MgCl2 with metallic lithium and exploiting naphthalene as an electron carrier: the lithium–naphthalene complex acts as the real reducing agent. Firstly, the nanocrystal particles were coated with the ligand 12-ethoxy ester dodecanehydroxamic acid, and then entrapped into water-dispersible polymeric micelles (PMs) made of the FDA-approved PLGA-b-PEG-COOH copolymer using the oil-in-water emulsion technique. Lately, we developed a more straightforward methodology by introducing chitosan, a highly biocompatible natural product, at the beginning of the process, simultaneously using lithium–naphthalene complex, thus having a one-pot procedure for the formation and surface modification of MgNPs. The obtained MgNPs were purified and fully characterized, showing diameters in the range of 50-300 nm. Notably, when coated with chitosan the particles remained stable as dry powder for more than 10 months. We proved the possibility of generating a temperature rise of a few to several degrees once MgNPs were illuminated using a 810 nm diode laser operating in continuous wave mode: the temperature rise resulted significant (0-15 °C) and concentration dependent. We then investigated potential cytotoxicity of the MgNPs: we used HN13 epithelial cells, derived from a head and neck squamous cell carcinoma and the hepa1-6 cell line, derived from hepatocellular carcinoma and very low toxicity was observed for both nanosystems. Finally, in vivo photothermal therapy was performed on xenograft hepa1-6 tumor bearing mice: the animals were treated with MgNPs coated with chitosan and showed no sign of suffering after the injection. After 12 hours the tumor was exposed to near-infrared laser light. The results clearly showed an extensive damage to tumor tissue after only 2 minutes of laser irradiation at 3Wcm-1, while no damage was reported when the tumor was treated with the laser and saline alone in control group. Despite the lower photothermal efficiency of Mg with respect to Au NPs, we consider MgNPs a promising, safe and green candidate for future clinical translations.

Keywords: chitosan, magnesium nanoparticles, nanomedicine, photothermal therapy

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Authors: Casey Keenan Joiner, Shayna Tayloe

Abstract:

Classical voice training for the novice singer has long relied on the guidance and instruction of vocalise collections, such as those written and compiled by Marchesi, Lütgen, Vaccai, and Lamperti. These vocalise collections purport to encourage healthy vocal habits and instill technical longevity in both aspiring and established singers, though their scope has long been somewhat confined to the classical idiom. For pedagogues and students specializing in other vocal genres, such as musical theatre and CCM (contemporary commercial music,) low-impact and pertinent vocal training aids are in short supply, and much of the suggested literature derives from classical methodology. While the tenants of healthy vocal production remain ubiquitous, specific stylistic needs and technical emphases differ from genre to genre and may require a specified extension of vocal acuity. As musical theatre continues to grow in popularity at both the professional and collegiate levels, the need for specialized training grows as well. Pedagogical literature geared specifically towards musical theatre (MT) singing and vocal production, while relatively uncommon, is readily accessible to the contemporary educator. Practitioners such as Norman Spivey, Mary Saunders Barton, Claudia Friedlander, Wendy Leborgne, and Marci Rosenberg continue to publish relevant research in the field of musical theatre voice pedagogy and have successfully identified many common MT vocal faults, their subsequent diagnoses, and their eventual corrections. Where classical methodology would suggest specific vocalises or training exercises to maintain corrected vocal posture following successful fault diagnosis, musical theatre finds itself without a relevant body of work towards which to transition. By analyzing the existing vocalise literature by means of a specialized set of parameters, including but not limited to melodic variation, rhythmic complexity, vowel utilization, and technical targeting, we have composed a set of vocalises meant specifically to address the training and conditioning of adult musical theatre voices. These vocalises target many pedagogical tenants in the musical theatre genre, including but not limited to thyroarytenoid-dominant production, twang resonance, lateral vowel formation, and “belt-mix.” By implementing these vocalises in the musical theatre voice studio, pedagogues can efficiently communicate proper musical theatre vocal posture and kinesthetic connection to their students, regardless of age or level of experience. The composition of these vocalises serves MT pedagogues on both a technical level as well as a sociological one. MT is a relative newcomer on the collegiate stage and the academization of musical theatre methodologies has been a slow and arduous process. The conflation of classical and MT techniques and training methods has long plagued the world of voice pedagogy and teachers often find themselves in positions of “cross-training,” that is, teaching students of both genres in one combined voice studio. As MT continues to establish itself on academic platforms worldwide, genre-specific literature and focused studies are both rare and invaluable. To ensure that modern students receive exacting and definitive training in their chosen fields, it becomes increasingly necessary for genres such as musical theatre to boast specified literature and a collection of musical theatre-specific vocalises only aids in this effort. This collection of musical theatre vocalises is the first of its kind and provides genre-specific studios with a basis upon which to grow healthy, balanced voices built for the harsh conditions of the modern theatre stage.

Keywords: voice pedagogy, targeted methodology, musical theatre, singing

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Authors: Vishal Kumar, Soumitra Satapathi

Abstract:

Föster Resonance Energy Transfer (FRET) is a powerful technique used to probe close-range molecular interactions. Physically, the FRET phenomenon manifests as a dipole–dipole interaction between closely juxtaposed fluorescent molecules (10–100 Å). Our effort is to employ this FRET technique to make a prototype device for highly sensitive detection of environment pollutant. Among the most common environmental pollutants, nitroaromatic compounds (NACs) are of particular interest because of their durability and toxicity. That’s why, sensitive and selective detection of small amounts of nitroaromatic explosives, in particular, 2,4,6-trinitrophenol (TNP), 2,4-dinitrotoluene (DNT) and 2,4,6-trinitrotoluene (TNT) has been a critical challenge due to the increasing threat of explosive-based terrorism and the need of environmental monitoring of drinking and waste water. In addition, the excessive utilization of TNP in several other areas such as burn ointment, pesticides, glass and the leather industry resulted in environmental accumulation, and is eventually contaminating the soil and aquatic systems. To the date, high number of elegant methods, including fluorimetry, gas chromatography, mass, ion-mobility and Raman spectrometry have been successfully applied for explosive detection. Among these efforts, fluorescence-quenching methods based on the mechanism of FRET show good assembly flexibility, high selectivity and sensitivity. Here, we report a FRET-based sensor system for the highly selective detection of NACs, such as TNP, DNT and TNT. The sensor system is composed of a copolymer Poly [(N,N-dimethylacrylamide)-co-(Boc-Trp-EMA)] (RP) bearing tryptophan derivative in the side chain as donor and dansyl tagged copolymer P(MMA-co-Dansyl-Ala-HEMA) (DCP) as an acceptor. Initially, the inherent fluorescence of RP copolymer is quenched by non-radiative energy transfer to DCP which only happens once the two molecules are within Förster critical distance (R0). The excellent spectral overlap (Jλ= 6.08×10¹⁴ nm⁴M⁻¹cm⁻¹) between donors’ (RP) emission profile and acceptors’ (DCP) absorption profile makes them an exciting and efficient FRET pair i.e. further confirmed by the high rate of energy transfer from RP to DCP i.e. 0.87 ns⁻¹ and lifetime measurement by time correlated single photon counting (TCSPC) to validate the 64% FRET efficiency. This FRET pair exhibited a specific fluorescence response to NACs such as DNT, TNT and TNP with 5.4, 2.3 and 0.4 µM LODs, respectively. The detection of NACs occurs with high sensitivity by photoluminescence quenching of FRET signal induced by photo-induced electron transfer (PET) from electron-rich FRET pair to electron-deficient NAC molecules. The estimated stern-volmer constant (KSV) values for DNT, TNT and TNP are 6.9 × 10³, 7.0 × 10³ and 1.6 × 104 M⁻¹, respectively. The mechanistic details of molecular interactions are established by time-resolved fluorescence, steady-state fluorescence and absorption spectroscopy confirmed that the sensing process is of mixed type, i.e. both dynamic and static quenching as lifetime of FRET system (0.73 ns) is reduced to 0.55, 0.57 and 0.61 ns DNT, TNT and TNP, respectively. In summary, the simplicity and sensitivity of this novel FRET sensor opens up the possibility of designing optical sensor of various NACs in one single platform for developing multimodal sensor for environmental monitoring and future field based study.

Keywords: FRET, nitroaromatic, stern-Volmer constant, tryptophan and dansyl tagged copolymer

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Authors: Jun Wang, Chenglei Diao, Emanuele Pagone, Jialuo Ding, Stewart Williams

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As a crucial component in aircraft, landing gear systems are responsible for supporting the plane during parking, taxiing, takeoff, and landing. Given the need for high load-bearing capacity over extended periods, 300M ultra-high strength steel (UHSS) is often the material of choice for crafting these systems due to its exceptional strength, toughness, and fatigue resistance. In the quest for cost-effective and sustainable manufacturing solutions, Wire Arc Additive Manufacturing (WAAM) emerges as a promising alternative for fabricating 300M UHSS landing gears. This is due to its advantages in near-net-shape forming of large components, cost-efficiency, and reduced lead times. Cranfield University has conducted an extensive preliminary study on WAAM 300M UHSS, covering feature deposition, interface analysis, and post-heat treatment. Both Gas Metal Arc (GMA) and Plasma Transferred Arc (PTA)-based WAAM methods were explored, revealing their feasibility for defect-free manufacturing. However, as-deposited 300M features showed lower strength but higher ductility compared to their forged counterparts. Subsequent post-heat treatments were effective in normalising the microstructure and mechanical properties, meeting qualification standards. A 300M UHSS landing gear demonstrator was successfully created using PTA-based WAAM, showcasing the method's precision and cost-effectiveness. The demonstrator, measuring Ф200mm x 700mm, was completed in 16 hours, using 7 kg of material at a deposition rate of 1.3kg/hr. This resulted in a significant reduction in the Buy-to-Fly (BTF) ratio compared to traditional manufacturing methods, further validating WAAM's potential for this application. A "cradle-to-gate" environmental impact assessment, which considers the cumulative effects from raw material extraction to customer shipment, has revealed promising outcomes. Utilising Wire Arc Additive Manufacturing (WAAM) for landing gear components significantly reduces the need for raw material extraction and refinement compared to traditional subtractive methods. This, in turn, lessens the burden on subsequent manufacturing processes, including heat treatment, machining, and transportation. Our estimates indicate that the carbon footprint of the component could be halved when switching from traditional machining to WAAM. Similar reductions are observed in embodied energy consumption and other environmental impact indicators, such as emissions to air, water, and land. Additionally, WAAM offers the unique advantage of part repair by redepositing only the necessary material, a capability not available through conventional methods. Our research shows that WAAM-based repairs can drastically reduce environmental impact, even when accounting for additional transportation for repairs. Consequently, WAAM emerges as a pivotal technology for reducing environmental impact in manufacturing, aiding the industry in its crucial and ambitious journey towards Net Zero. This study paves the way for transformative benefits across the aerospace industry, as we integrate manufacturing into a hybrid solution that offers substantial savings and access to more sustainable technologies for critical component production.

Keywords: WAAM, aircraft landing gear, microstructure, mechanical performance, life cycle assessment

Procedia PDF Downloads 121

Authors: Mary-Ann N. Jallad, Dalal F. Jaber, Alexander M. Abdelnoor

Abstract:

Introduction: Current evidence confirms that both innate and adaptive immune systems are capable of recognizing and abolishing malignant cells. The emergence of cancerous tumors in patients is, therefore, an indication that certain cancer cells can resist elimination by the immune system through a process known as “immune evasion”. In fact, cancer cells often exploit regulatory mechanisms to escape immunity. Such mechanisms normally exist to control the immune responses and prohibit exaggerated or autoimmune reactions. Recently, immunotherapies have shown promising yet limited results. Therefore this study investigates several immunotherapeutic combinations and devises a triple immunotherapy which harnesses the innate and acquired immune responses towards the annihilation of malignant cells through overcoming their ability of immune evasion, consequently hampering malignant progression and eliminating established tumors. The aims of the study are to rule out acute/chronic toxic effects of the proposed treatment combinations, to assess the effect of these combinations on tumor growth and survival rates, and to investigate potential mechanisms underlying the phenotypic results through analyzing serum levels of anti-tumor cytokines, angiogenic factors and tumor progression indicator, and the tumor-infiltrating immune-cells populations. Methodology: For toxicity analysis, cancer-free C57BL/6 mice are randomized into 9 groups: Group 1 untreated, group 2 treated with sterile saline (solvent of used treatments), group 3 treated with Monophosphoryl-lipid-A, group 4 with anti-CTLA4-antibodies, group 5 with 1-Methyl-Tryptophan (Indolamine-Dioxygenase-1 inhibitor), group 6 with both MPLA and anti-CTLA4-antibodies, group 7 with both MPLA and 1-MT, group 8 with both anti-CTLA4-antibodies and 1-MT, and group 9 with all three: MPLA, anti-CTLA4-antibodies and 1-MT. Mice are monitored throughout the treatment period and for three following months. At that point, histological sections from their main organs are assessed. For tumor progression and survival analysis, a murine melanoma model is generated by injecting analogous mice with B16F10 melanoma cells. These mice are segregated into the listed nine groups. Their tumor size and survival are monitored. For a depiction of underlying mechanisms, melanoma-bearing mice from each group are sacrificed at several time-points. Sera are tested to assess the levels of Interleukin-12 (IL-12), Vascular-Endothelial-Growth Factor (VEGF), and S100B. Furthermore, tumors are excised for analysis of infiltrated immune cell populations including T-cells, macrophages, natural killer cells and immune-regulatory cells. Results: Toxicity analysis shows that all treated groups present no signs of neither acute nor chronic toxicity. Their appearance and weights were comparable to those of control groups throughout the treatment period and for the following 3 months. Moreover, histological sections from their hearts, kidneys, lungs, and livers were normal. Work is ongoing for completion of the remaining study aims. Conclusion: Toxicity was the major concern for the success of the proposed comprehensive combinational therapy. Data generated so far ruled out any acute or chronic toxic effects. Consequently, ongoing work is quite promising and may significantly contribute to the development of more effective immunotherapeutic strategies for the treatment of cancer patients.

Keywords: cancer immunotherapy, check-point blockade, combination therapy, melanoma

Procedia PDF Downloads 92

Authors: Mehmet Salih Bayraktutan

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Geomechanical properties of Rock Salt Deposits in Tuzluca Salt Mine Area (Eastern Turkey) are studied for modeling the operation- excavation strategy. The purpose of this research focused on calculating the critical value of span height- which will meet the safety requirements. The Mine Site Tuzluca Hills consist of alternating parallel bedding of Salt ( NaCl ) and Gypsum ( CaS04 + 2 H20) rocks. Rock Salt beds are more resistant than narrow Gypsum interlayers. Rock Salt beds formed almost 97 percent of the total height of the Hill. Therefore, the geotechnical safety of Galleries depends on the mechanical criteria of Rock Salt Cores. General deposition of Tuzluca Basin was finally completed by Tuzluca Evaporites, as for the uppermost stratigraphic unit. They are currently running mining operations performed by classic mechanical excavation, room and pillar method. Rooms and Pillars are currently experiencing an initial stage of fracturing in places. Geotechnical safety of the whole mining area evaluated by Rock Mass Rating (RMR), Rock Quality Designation (RQD) spacing of joints, and the interaction of groundwater and fracture system. In general, bedded rock salt Show large lateral deformation capacity (while deformation modulus stays in relative small values, here E= 9.86 GPa). In such litho-stratigraphic environments, creep is a critical mechanism in failure. Rock Salt creep rate in steady-state is greater than interbedding layers. Under long-lasted compressive stresses, creep may cause shear displacements, partly using bedding planes. Eventually, steady-state creep in time returns to accelerated stages. Uniaxial compression creep tests on specimens were performed to have an idea of rock salt strength. To give an idea, on Rock Salt cores, average axial strength and strain are found as 18 - 24 MPa and 0.43-0.45 %, respectively. Uniaxial Compressive strength of 26- 32 MPa, from bedded rock salt cores. Elastic modulus is comparatively low, but lateral deformation of the rock salt is high under the uniaxial compression stress state. Poisson ratio = 0.44, break load = 156 kN, cohesion c= 12.8 kg/cm2, specific gravity SG=2.17 gr/cm3. Fracture System; spacing of fractures, joints, faults, offsets are evaluated under acting geodynamic mechanism. Two sand beds, each 4-6 m thick, exist near to upper level and at the top of the evaporating sequence. They act as aquifers and keep infiltrated water on top for a long duration, which may result in the failure of roofs or pillars. Two major active seismic ( N30W and N70E ) striking Fault Planes and parallel fracture strands have seismically triggered moderate risk of structural deformation of rock salt bedding sequence. Earthquakes and Floods are two prevailing sources of geohazards in this region—the seismotectonic activity of the Mine Site based on the crossing framework of Kagizman Faults and Igdir Faults. Dominant Hazard Risk sources include; a) Weak mechanical properties of rock salt, gypsum, anhydrite beds-creep. b) Physical discontinuities cutting across the thick parallel layers of Evaporite Mass, c) Intercalated beds of weak cemented or loose sand, clayey sandy sediments. On the other hand, absorbing the effects of salt-gyps parallel bedded deposits on seismic wave amplitudes has a reducing effect on the Rock Mass.

Keywords: bedded rock salt, creep, failure mechanism, geotechnical safety

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Authors: Zeynep Busra Velioglu, Deniz Pulat, Beril Demirbakan, Burak Ozcan, Ece Bayrak, Cevat Erisken

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Bone tissue has the ability to perform a wide array of functions including providing posture, load-bearing capacity, protection for the internal organs, initiating hematopoiesis, and maintaining the homeostasis of key electrolytes via calcium/phosphate ion storage. The most common cause for bone defects is extensive trauma and subsequent infection. Bone tissue has the self-healing capability without a scar tissue formation for the majority of the injuries. However, some may result with delayed union or fracture non-union. Such cases include reconstruction of large bone defects or cases of compromised regenerative process as a result of avascular necrosis and osteoporosis. Several surgical methods exist to treat bone defects, including Ilizarov method, Masquelete technique, growth factor stimulation, and bone replacement. Unfortunately, these are technically demanding and come with noteworthy disadvantages such as lengthy treatment duration, adverse effects on the patient’s psychology, repeated surgical procedures, and often long hospitalization times. These limitations associated with surgical techniques make bone substitutes an attractive alternative. Here, it was hypothesized that a 3D printed scaffold will mimic trabecular bone in terms of biomechanical properties and that such scaffolds will support cell attachment and survival. To test this hypothesis, this study aimed at fabricating poly(lactic acid), PLA, structures using 3D printing technology for trabecular bone defects, characterizing the scaffolds and comparing with bovine trabecular bone. Capacity of scaffolds on human bone marrow stem cell (hBMSC) attachment and survival was also evaluated. Cubes with a volume of 1 cm³ having pore sizes of 0.50, 1.00 and 1.25 mm were printed. The scaffolds/grafts were characterized in terms of porosity, contact angle, compressive mechanical properties as well cell response. Porosities of the 3D printed scaffolds were calculated based on apparent densities. For contact angles, 50 µl distilled water was dropped over the surface of scaffolds, and contact angles were measured using ‘Image J’ software. Mechanical characterization under compression was performed on scaffolds and native trabecular bone (bovine, 15 months) specimens using a universal testing machine at a rate of 0.5mm/min. hBMSCs were seeded onto the 3D printed scaffolds. After 3 days of incubation with fully supplemented Dulbecco’s modified Eagle’s medium, the cells were fixed using 2% formaldehyde and glutaraldehyde mixture. The specimens were then imaged under scanning electron microscopy. Cell proliferation was determined by using EZQuant dsDNA Quantitation kit. Fluorescence was measured using microplate reader Spectramax M2 at the excitation and emission wavelengths of 485nm and 535nm, respectively. Findings suggested that porosity of scaffolds with pore dimensions of 0.5mm, 1.0mm and 1.25mm were not affected by pore size, while contact angle and compressive modulus decreased with increasing pore size. Biomechanical characterization of trabecular bone yielded higher modulus values as compared to scaffolds with all pore sizes studied. Cells attached and survived in all surfaces, demonstrating higher proliferation on scaffolds with 1.25mm pores as compared with those of 1mm. Collectively, given lower mechanical properties of scaffolds as compared to native bone, and biocompatibility of the scaffolds, the 3D printed PLA scaffolds of this study appear as candidate substitutes for bone repair and regeneration.

Keywords: 3D printing, biomechanics, bone repair, stem cell

Procedia PDF Downloads 151