Search results for: Magnetic resonance imaging

Authors: Langhit Kurar, Loren Charles

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Introduction: In light of recent BOAST 12 (August 2016) published guidance on management of ankle fractures, the project aimed to highlight key discrepancies throughout the care trajectory from admission to point of discharge at a district general hospital. Wide breadth of data covering three key domains: accident and emergency, radiology, and orthopaedic surgery were subsequently stratified and recommendations on note documentation, and outpatient follow up were made. Methods: A retrospective twelve month audit was conducted reviewing results of ankle fracture management in 37 patients. Inclusion criterion involved all patients seen at Darent Valley Hospital (DVH) emergency department with radiographic evidence of an ankle fracture. Exclusion criterion involved all patients managed solely by nursing staff or having sustained purely ligamentous injury. Medical notes, including discharge summaries and the PACS online radiographic tool were used for data extraction. Results: Cross-examination of the A & E domain revealed limited awareness of the BOAST 12 recent publication including requirements to document skin integrity and neurovascular assessment. This had direct implications as this would have changed the surgical plan for acutely compromised patients. The majority of results obtained from the radiographic domain were satisfactory with appropriate X-rays taken in over 95% of cases. However, due to time pressures within A & E, patients were often left without a post manipulation XRAY in a backslab. Poorly reduced fractures were subsequently left for a long period resulting in swollen ankles and a time-dependent lag to surgical intervention. This had knocked on implications for prolonged inpatient stay resulting in hospital-acquired co-morbidity including pressure sores. Discussion: The audit has highlighted several areas of improvement throughout the disease trajectory from review in the emergency department to follow up as an outpatient. This has prompted the creation of an algorithm to ensure patients with significant fractures presenting to the emergency department are seen promptly and treatment expedited as per recent guidance. This includes timing for X-rays taken in A & E. Re-audit has shown significant improvement in both documentation at time of presentation and appropriate follow-up strategies. Within the orthopedic domain, we are in the process of creating an ankle fracture pathway to ensure imaging and weight bearing status are made clear to the consulting clinicians in an outpatient setting. Significance/Clinical Relevance: As a result of the ankle fracture algorithm we have adapted the BOAST 12 guidance to shape an intrinsic pathway to not only improve patient management within the emergency department but also create a standardised format for follow up.

Keywords: ankle, fracture, BOAST, radiology

Procedia PDF Downloads 153

Authors: D. Ficai, A. Ficai, D. Gudovan, I. A. Gudovan, I. Ardelean, R. Trusca, E. Andronescu, V. Mitran, A. Cimpean

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In the last years, scientists struggled hardly to mimic bone structures to develop implants and biostructures which present higher biocompatibility and reduced rejection rate. One way to obtain this goal is to use similar materials as that of bone, namely collagen/hydroxyapatite composite materials. However, it is very important to tailor both compositions but also the microstructure of the bone that would ensure both the optimal osteointegartion and the mechanical properties required by the application. In this study, new collagen/hydroxyapatites composite materials doped with Cu, Li, Mn, Zn were successfully prepared. The synthesis method is described below: weight the Ca(OH)₂ mass, i.e., 7,3067g, and ZnCl₂ (0.134g), CuSO₄ (0.159g), LiCO₃ (0.133g), MnCl₂.4H₂O (0.1971g), and suspend in 100ml distilled water under magnetic stirring. The solution thus obtained is added a solution of NaH₂PO₄*H2O (8.247g dissolved in 50ml distilled water) under slow dropping of 1 ml/min followed by adjusting the pH to 9.5 with HCl and finally filter and wash until neutral pH. The as-obtained slurry was dried in the oven at 80°C and then calcined at 600°C in order to ensure a proper purification of the final product of organic phases, also inducing a proper sterilization of the mixture before insertion into the collagen matrix. The collagen/hydroxyapatite composite materials are tailored from morphological point of view to optimize their biocompatibility and bio-integration against mechanical properties whereas the addition of the dopants is aimed to improve the biological activity of the samples. The addition of transitional metals can improve the biocompatibility and especially the osteoblasts adhesion (Mn²⁺) or to induce slightly better osteoblast differentiation of the osteoblast, Zn²⁺ being a cofactor for many enzymes including those responsible for cell differentiation. If the amount is too high, the final material can become toxic and lose all of its biocompatibility. In order to achieve a good biocompatibility and not reach the cytotoxic effect, the amount of transitional metals added has to be maintained at low levels (0.5% molar). The amount of transitional metals entering into the elemental cell of HA will be verified using inductively-coupled plasma mass spectrometric system. This highly sensitive technique is necessary, because, at such low levels of transitional metals, the difference between biocompatible and cytotoxic is a very thin line, thus requiring proper and thorough investigation using a precise technique. In order to determine the structure and morphology of the obtained composite materials, IR spectroscopy, X-Ray diffraction (XRD), scanning electron microscopy (SEM), and Energy Dispersive X-Ray Spectrometry (EDS) were used. Acknowledgment: The present work was possible due to the EU-funding grant POSCCE-A2O2.2.1-2013-1, Project No. 638/12.03.2014, code SMIS-CSNR 48652. The financial contribution received from the national project “Biomimetic porous structures obtained by 3D printing developed for bone tissue engineering (BIOGRAFTPRINT), No. 127PED/2017 is also highly acknowledged.

Keywords: collagen, composite materials, hydroxyapatite, bone tissue engineering

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Authors: Poojan Gharat, Haridas Pal, Sharmistha Dutta Choudhury

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Tuning photophysical properties of guest dyes through host-guest interactions involving macrocyclic hosts are the attractive research areas since past few decades, as these changes can directly be implemented in chemical sensing, molecular recognition, fluorescence imaging and dye laser applications. Excited state intramolecular proton transfer (ESIPT) is an intramolecular prototautomerization process display by some specific dyes. The process is quite amenable to tunability by the presence of different macrocyclic hosts. The present study explores the interesting effect of p-sulfonatocalix[n]arene (SCXn) and cyclodextrin (CD) hosts on the excited-state prototautomeric equilibrium of Chrysazine (CZ), a model antitumour drug. CZ exists exclusively in its normal form (N) in the ground state. However, in the excited state, the excited N* form undergoes ESIPT along with its pre-existing intramolecular hydrogen bonds, giving the excited state prototautomer (T*). Accordingly, CZ shows a single absorption band due to N form, but two emission bands due to N* and T* forms. Facile prototautomerization of CZ is considerably inhibited when the dye gets bound to SCXn hosts. However, in spite of lower binding affinity, the inhibition is more profound with SCX6 host as compared to SCX4 host. For CD-CZ system, while prototautomerization process is hindered by the presence of β-CD, it remains unaffected in the presence of γCD. Reduction in the prototautomerization process of CZ by SCXn and βCD hosts is unusual, because T* form is less dipolar in nature than the N*, hence binding of CZ within relatively hydrophobic hosts cavities should have enhanced the prototautomerization process. At the same time, considering the similar chemical nature of two CD hosts, their effect on prototautomerization process of CZ would have also been similar. The atypical effects on the prototautomerization process of CZ by the studied hosts are suggested to arise due to the partial inclusion or external binding of CZ with the hosts. As a result, there is a strong possibility of intermolecular H-bonding interaction between CZ dye and the functional groups present at the portals of SCXn and βCD hosts. Formation of these intermolecular H-bonds effectively causes the pre-existing intramolecular H-bonding network within CZ molecule to become weak, and this consequently reduces the prototautomerization process for the dye. Our results suggest that rather than the binding affinity between the dye and host, it is the orientation of CZ in the case of SCXn-CZ complexes and the binding stoichiometry in the case of CD-CZ complexes that play the predominant role in influencing the prototautomeric equilibrium of the dye CZ. In the case of SCXn-CZ complexes, the results obtained through experimental findings are well supported by quantum chemical calculations. Similarly for CD-CZ systems, binding stoichiometries obtained through geometry optimization studies on the complexes between CZ and CD hosts correlate nicely with the experimental results. Formation of βCD-CZ complexes with 1:1 stoichiometry while formation of γCD-CZ complexes with 1:1, 1:2 and 2:2 stoichiometries are revealed from geometry optimization studies and these results are in good accordance with the observed effects by the βCD and γCD hosts on the ESIPT process of CZ dye.

Keywords: intermolecular proton transfer, macrocyclic hosts, quantum chemical studies, photophysical studies

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Authors: Radik D. Aglyamov, Alexander K. Naumov, Alexey A. Shavelev, Oleg A. Morozov, Arsenij D. Shishkin, Yury P.Brodnikovsky, Alexander A.Karabutov, Alexander A. Oraevsky, Vadim V. Semashko

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The development of medical optoacoustic tomography with the using human blood as endogenic contrast agent is constrained by the lack of reliable, easy-to-use and inexpensive sources of high-power pulsed laser radiation in the spectral region of 750-900 nm [1-2]. Currently used titanium-sapphire, alexandrite lasers or optical parametric light oscillators do not provide the required and stable output characteristics, they are structurally complex, and their cost is up to half the price of diagnostic optoacoustic systems. Here we are developing the lasers based on Cr:LiCaAlF6 crystals which are free of abovementioned disadvantages and provides intensive ten’s ns-range tunable laser radiation at specific absorption bands of oxy- (~840 nm) and -deoxyhemoglobin (~757 nm) in the blood. Cr:LiCAF (с=3 at.%) crystals were grown in Kazan Federal University by the vertical directional crystallization (Bridgman technique) in graphite crucibles in a fluorinating atmosphere at argon overpressure (P=1500 hPa) [3]. The laser elements have cylinder shape with the diameter of 8 mm and 90 mm in length. The direction of the optical axis of the crystal was normal to the cylinder generatrix, which provides the π-polarized laser action correspondent to maximal stimulated emission cross-section. The flat working surfaces of the active elements were polished and parallel to each other with an error less than 10”. No any antireflection coating was applied. The Q-switched master oscillator-power amplifiers laser system (MOPA) with the dual-Xenon flashlamp pumping scheme in diffuse-reflectivity close-coupled head were realized. A specially designed laser cavity, consisting of dielectric highly reflective reflectors with a 2 m-curvature radius, a flat output mirror, a polarizer and Q-switch sell, makes it possible to operate sequentially in a circle (50 ns - laser one pulse after another) at wavelengths of 757 and 840 nm. The programmable pumping system from Tomowave Laser LLC (Russia) provided independent to each pulses (up to 250 J at 180 μs) pumping to equalize the laser radiation intensity at these wavelengths. The MOPA laser operates at 10 Hz pulse repetition rate with the output energy up to 210 mJ. Taking into account the limitations associated with physiological movements and other characteristics of patient tissues, the duration of laser pulses and their energy allows molecular and functional high-contrast imaging to depths of 5-6 cm with a spatial resolution of at least 1 mm. Highly likely the further comprehensive design of laser allows improving the output properties and realizing better spatial resolution of medical multispectral optoacoustic tomography systems.

Keywords: medical optoacoustic, endogenic contrast agent, multiwavelength tunable pulse lasers, MOPA laser system

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Authors: Sardorbek Numonov, Hyohun Kim, Dongwha Shin, Yeonseok Kim, Ji-Su Ahn, Dongeun Choi, Byung-Woo Hong

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The detection of curvilinear structures often plays an important role in the analysis of images. In particular, it is considered as a crucial step for the diagnosis of chronic respiratory diseases to localize the fissures in chest CT imagery where the lung is divided into five lobes by the fissures that are characterized by linear features in appearance. However, the characteristic linear features for the fissures are often shown to be subtle due to the high intensity variability, pathological deformation or image noise involved in the imaging procedure, which leads to the uncertainty in the quantification of anatomical or functional properties of the lung. Thus, it is desired to enhance the linear features present in the chest CT images so that the distinctiveness in the delineation of the lobe is improved. We propose a recursive diffusion process that prefers coherent features based on the analysis of structure tensor in an anisotropic manner. The local image features associated with certain scales and directions can be characterized by the eigenanalysis of the structure tensor that is often regularized via isotropic diffusion filters. However, the isotropic diffusion filters involved in the computation of the structure tensor generally blur geometrically significant structure of the features leading to the degradation of the characteristic power in the feature space. Thus, it is required to take into consideration of local structure of the feature in scale and direction when computing the structure tensor. We apply an anisotropic diffusion in consideration of scale and direction of the features in the computation of the structure tensor that subsequently provides the geometrical structure of the features by its eigenanalysis that determines the shape of the anisotropic diffusion kernel. The recursive application of the anisotropic diffusion with the kernel the shape of which is derived from the structure tensor leading to the anisotropic scale-space where the geometrical features are preserved via the eigenanalysis of the structure tensor computed from the diffused image. The recursive interaction between the anisotropic diffusion based on the geometry-driven kernels and the computation of the structure tensor that determines the shape of the diffusion kernels yields a scale-space where geometrical properties of the image structure are effectively characterized. We apply our recursive anisotropic diffusion algorithm to the detection of curvilinear structure in the chest CT imagery where the fissures present curvilinear features and define the boundary of lobes. It is shown that our algorithm yields precise detection of the fissures while overcoming the subtlety in defining the characteristic linear features. The quantitative evaluation demonstrates the robustness and effectiveness of the proposed algorithm for the detection of fissures in the chest CT in terms of the false positive and the true positive measures. The receiver operating characteristic curves indicate the potential of our algorithm as a segmentation tool in the clinical environment. This work was supported by the MISP(Ministry of Science and ICT), Korea, under the National Program for Excellence in SW (20170001000011001) supervised by the IITP(Institute for Information and Communications Technology Promotion).

Keywords: anisotropic diffusion, chest CT imagery, chronic respiratory disease, curvilinear structure, fissure detection, structure tensor

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Authors: Kumari Sweta, Ajanta Goswami, Abhilasha Dixit

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Landslide is a geomorphic process that plays an essential role in the evolution of the hill-slope and long-term landscape evolution. But its abrupt nature and the associated catastrophic forces of the process can have undesirable socio-economic impacts, like substantial economic losses, fatalities, ecosystem, geomorphologic and infrastructure disturbances. The estimated fatality rate is approximately 1person /100 sq. Km and the average economic loss is more than 550 crores/year in the Himalayan belt due to landslides. This study presents a comparative performance of a statistical bivariate method and a machine learning technique for landslide susceptibility mapping in and around Dharamshala, Himachal Pradesh. The final produced landslide susceptibility maps (LSMs) with better accuracy could be used for land-use planning to prevent future losses. Dharamshala, a part of North-western Himalaya, is one of the fastest-growing tourism hubs with a total population of 30,764 according to the 2011 census and is amongst one of the hundred Indian cities to be developed as a smart city under PM’s Smart Cities Mission. A total of 209 landslide locations were identified in using high-resolution linear imaging self-scanning (LISS IV) data. The thematic maps of parameters influencing landslide occurrence were generated using remote sensing and other ancillary data in the GIS environment. The landslide causative parameters used in the study are slope angle, slope aspect, elevation, curvature, topographic wetness index, relative relief, distance from lineaments, land use land cover, and geology. LSMs were prepared using information value (Info Val), and Fuzzy Expert System (FES) models. Info Val is a statistical bivariate method, in which information values were calculated as the ratio of the landslide pixels per factor class (Si/Ni) to the total landslide pixel per parameter (S/N). Using this information values all parameters were reclassified and then summed in GIS to obtain the landslide susceptibility index (LSI) map. The FES method is a machine learning technique based on ‘mean and neighbour’ strategy for the construction of fuzzifier (input) and defuzzifier (output) membership function (MF) structure, and the FR method is used for formulating if-then rules. Two types of membership structures were utilized for membership function Bell-Gaussian (BG) and Trapezoidal-Triangular (TT). LSI for BG and TT were obtained applying membership function and if-then rules in MATLAB. The final LSMs were spatially and statistically validated. The validation results showed that in terms of accuracy, Info Val (83.4%) is better than BG (83.0%) and TT (82.6%), whereas, in terms of spatial distribution, BG is best. Hence, considering both statistical and spatial accuracy, BG is the most accurate one.

Keywords: bivariate statistical techniques, BG and TT membership structure, fuzzy expert system, information value method, machine learning technique

Procedia PDF Downloads 101

Authors: Kyoungrean Kim

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Importance of deep-sea mineral resources is dramatically increasing due to the depletion of land mineral resources corresponding to increasing human’s economic activities. Korea has acquired exclusive exploration licenses at four areas which are the Clarion-Clipperton Fracture Zone in the Pacific Ocean (2002), Tonga (2008), Fiji (2011) and Indian Ocean (2014). The preparation for commercial mining of Nautilus minerals (Canada) and Lockheed martin minerals (USA) is expected by 2020. The London Protocol 1996 (LP) under International Maritime Organization (IMO) and International Seabed Authority (ISA) will set environmental guidelines for deep-sea mining until 2020, to protect marine environment. In this research, the applicability of washing/extraction treatment for the remediation of deep-sea mining tailings was mainly evaluated in order to present preliminary data to develop practical remediation technology in near future. Polymetallic nodule samples were collected at the Clarion-Clipperton Fracture Zone in the Pacific Ocean, then stored at room temperature. Samples were pulverized by using jaw crusher and ball mill then, classified into 3 particle sizes (> 63 µm, 63-20 µm, < 20 µm) by using vibratory sieve shakers (Analysette 3 Pro, Fritsch, Germany) with 63 µm and 20 µm sieve. Only the particle size 63-20 µm was used as the samples for investigation considering the lower limit of ore dressing process which is tens to 100 µm. Rhamnolipid and sodium alginate as biosurfactant and aluminum sulfate which are mainly used as flocculant were used as environmentally friendly additives. Samples were adjusted to 2% liquid with deionized water then mixed with various concentrations of additives. The mixture was stirred with a magnetic bar during specific reaction times and then the liquid phase was separated by a centrifugal separator (Thermo Fisher Scientific, USA) under 4,000 rpm for 1 h. The separated liquid was filtered with a syringe and acrylic-based filter (0.45 µm). The extracted heavy metals in the filtered liquid were then determined using a UV-Vis spectrometer (DR-5000, Hach, USA) and a heat block (DBR 200, Hach, USA) followed by US EPA methods (8506, 8009, 10217 and 10220). Polymetallic nodule was mainly composed of manganese (27%), iron (8%), nickel (1.4%), cupper (1.3 %), cobalt (1.3%) and molybdenum (0.04%). Based on remediation standards of various countries, Nickel (Ni), Copper (Cu), Cadmium (Cd) and Zinc (Zn) were selected as primary target materials. Throughout this research, the use of rhamnolipid was shown to be an effective approach for removing heavy metals in samples originated from manganese nodules. Sodium alginate might also be one of the effective additives for the remediation of deep-sea mining tailings such as polymetallic nodules. Compare to the use of rhamnolipid and sodium alginate, aluminum sulfate was more effective additive at short reaction time within 4 h. Based on these results, sequencing particle separation, selective extraction/washing, advanced filtration of liquid phase, water treatment without dewatering and solidification/stabilization may be considered as candidate technologies for the remediation of deep-sea mining tailings.

Keywords: deep-sea mining tailings, heavy metals, remediation, extraction, additives

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Authors: J. Martin, A. Nominé, T. Czerwiec, G. Henrion, T. Belmonte

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The plasma electrolytic oxidation (PEO) is a particular electrochemical process to produce protective oxide ceramic coatings on light-weight metals (Al, Mg, Ti). When applied to aluminum alloys, the resulting PEO coating exhibit improved wear and corrosion resistance because thick, hard, compact and adherent crystalline alumina layers can be achieved. Several investigations have been carried out to improve the efficiency of the PEO process and one particular way consists in tuning the suitable electrical regime. Despite the considerable interest in this process, there is still no clear understanding of the underlying discharge mechanisms that make possible metal oxidation up to hundreds of µm through the ceramic layer. A key parameter that governs the PEO process is the numerous short-lived micro-discharges (micro-plasma in liquid) that occur continuously over the processed surface when the high applied voltage exceeds the critical dielectric breakdown value of the growing ceramic layer. By using a bipolar pulsed current to supply the electrodes, we previously observed that micro-discharges are delayed with respect to the rising edge of the anodic current. Nevertheless, explanation of the origin of such phenomena is still not clear and needs more systematic investigations. The aim of the present communication is to identify the relationship that exists between this delay and the mechanisms responsible of the oxide growth. For this purpose, the delay of micro-discharges ignition is investigated as the function of various electrical parameters such as the current density (J), the current pulse frequency (F) and the anodic to cathodic charge quantity ratio (R = Qp/Qn) delivered to the electrodes. The PEO process was conducted on Al2214 aluminum alloy substrates in a solution containing potassium hydroxide [KOH] and sodium silicate diluted in deionized water. The light emitted from micro-discharges was detected by a photomultiplier and the micro-discharge parameters (number, size, life-time) were measured during the process by means of ultra-fast video imaging (125 kfr./s). SEM observations and roughness measurements were performed to characterize the morphology of the elaborated oxide coatings while XRD was carried out to evaluate the amount of corundum -Al203 phase. Results show that whatever the applied current waveform, the delay of micro-discharge appearance increases as the process goes on. Moreover, the delay is shorter when the current density J (A/dm2), the current pulse frequency F (Hz) and the ratio of charge quantity R are high. It also appears that shorter delays are associated to stronger micro-discharges (localized, long and large micro-discharges) which have a detrimental effect on the elaborated oxide layers (thin and porous). On the basis of the results, a model for the growth of the PEO oxide layers will be presented and discussed. Experimental results support that a mechanism of electrical charge accumulation at the oxide surface / electrolyte interface takes place until the dielectric breakdown occurs and thus until micro-discharges appear.

Keywords: aluminium, micro-discharges, oxidation mechanisms, plasma electrolytic oxidation

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Authors: Ting Lu, Ya-Ru Diao, Fei Fan, Ye Xue, Lei Shi, Xian-e Tang, Meng-jun Zhan, Zhen-hua Deng

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Accurate adult age estimation (AAE) is a significant and challenging task in forensic and archeology fields. Attempts have been made to explore optimal adult age metrics, and the rib is considered a potential age marker. The traditional way is to extract age-related features designed by experts from macroscopic or radiological images followed by classification or regression analysis. Those results still have not met the high-level requirements for practice, and the limitation of using feature design and manual extraction methods is loss of information since the features are likely not designed explicitly for extracting information relevant to age. Deep learning (DL) has recently garnered much interest in imaging learning and computer vision. It enables learning features that are important without a prior bias or hypothesis and could be supportive of AAE. This study aimed to develop DL models for AAE based on CT images and compare their performance to the manual visual scoring method. Chest CT data were reconstructed using volume rendering (VR). Retrospective data of 2500 patients aged 20.00-69.99 years were obtained between December 2019 and September 2021. Five-fold cross-validation was performed, and datasets were randomly split into training and validation sets in a 4:1 ratio for each fold. Before feeding the inputs into networks, all images were augmented with random rotation and vertical flip, normalized, and resized to 224×224 pixels. ResNeXt was chosen as the DL baseline due to its advantages of higher efficiency and accuracy in image classification. Mean absolute error (MAE) was the primary parameter. Independent data from 100 patients acquired between March and April 2022 were used as a test set. The manual method completely followed the prior study, which reported the lowest MAEs (5.31 in males and 6.72 in females) among similar studies. CT data and VR images were used. The radiation density of the first costal cartilage was recorded using CT data on the workstation. The osseous and calcified projections of the 1 to 7 costal cartilages were scored based on VR images using an eight-stage staging technique. According to the results of the prior study, the optimal models were the decision tree regression model in males and the stepwise multiple linear regression equation in females. Predicted ages of the test set were calculated separately using different models by sex. A total of 2600 patients (training and validation sets, mean age=45.19 years±14.20 [SD]; test set, mean age=46.57±9.66) were evaluated in this study. Of ResNeXt model training, MAEs were obtained with 3.95 in males and 3.65 in females. Based on the test set, DL achieved MAEs of 4.05 in males and 4.54 in females, which were far better than the MAEs of 8.90 and 6.42 respectively, for the manual method. Those results showed that the DL of the ResNeXt model outperformed the manual method in AAE based on CT reconstruction of the costal cartilage and the developed system may be a supportive tool for AAE.

Keywords: forensic anthropology, age determination by the skeleton, costal cartilage, CT, deep learning

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Authors: Chetna Dhand, Venkatesh Mayandi, Silvia Marrero Diaz, Roger W. Beuerman, Seeram Ramakrishna, Rajamani Lakshminarayanan

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Sturdy Insect Cuticle Sclerotization, Incredible Substrate independent Mussel’s bioadhesion, Tanning of Leather are some of catechol(amine)s mediated natural processes. Chemical contemplation spots toward a mechanism instigated with the formation of the quinone moieties from the respective catechol(amine)s, via oxidation, followed by the nucleophilic addition of the amino acids/proteins/peptides to this quinone leads to the development of highly strong, cross-linked and water-resistant proteinacious structures. Inspired with this remarkable catechol(amine)s chemistry towards amino acids/proteins/peptides, we attempted to design highly stable and water-resistant antifungal wound dressing mats with exceptional durability using collagen (protein), dopamine (catecholamine) and antifungal drugs (Amphotericin B and Caspofungin) as the key materials. Electrospinning technique has been used to fabricate desired nanofibrous mat including Collagen (COLL), COLL/Dopamine (COLL/DP) and calcium incorporated COLL/DP (COLL-DP-Ca2+). The prepared protein-based scaffolds have been studied for their microscopic investigations (SEM, TEM, and AFM), structural analysis (FT-IR), mechanical properties, water wettability characteristics and aqueous stability. Biocompatibility of these scaffolds has been analyzed for dermal fibroblast cells using MTS assay, Cell TrackerTM Green CMFDA and confocal imaging. Being the winner sample, COLL-DP-Ca2+ scaffold has been selected for incorporating two antifungal drugs namely Caspofungin (Peptide based) and Amphotericin B (Non-Peptide based). Antifungal efficiency of the designed mats has been evaluated for eight diverse fungal strains employing different microbial assays including disc diffusion, cell-viability assay, time kill kinetics etc. To confirm the durability of these mats, in term of their antifungal activity, drug leaching studies has been performed and monitored using disc diffusion assay each day. Ex-vivo fungal infection model has also been developed and utilized to validate the antifungal efficacy of the designed wound dressings. Results clearly reveal dopamine mediated crosslinking within COLL-antifungal scaffolds that leads to the generation of highly stable, mechanical tough, biocompatible wound dressings having the zone of inhabitation of ≥ 2 cm for almost all the investigated fungal strains. Leaching studies and Ex-vivo model has confirmed the durability of these wound dressing for more than 3 weeks and certified their suitability for commercialization. A model has also been proposed to enlighten the chemical mechanism involved for the development of these antifungal wound dressings with exceptional robustness.

Keywords: catecholamine chemistry, electrospinning technique, antifungals, wound dressings, collagen

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Authors: Igor B. Sivaev

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Design of molecular machines is an extraordinary growing and very important area of research that it was recognized by awarding Sauvage, Stoddart and Feringa the Nobel Prize in Chemistry in 2016 'for the design and synthesis of molecular machines'. Based on the type of motion being performed, molecular machines can be divided into two main types: molecular motors and molecular switches. Molecular switches are molecules or supramolecular complexes having bistability, i.e., the ability to exist in two or more stable forms, among which may be reversible transitions under external influence (heating, lighting, changing the medium acidity, the action of chemicals, exposure to magnetic or electric field). Molecular switches are the main structural element of any molecular electronics devices. Therefore, the design and the study of molecules and supramolecular systems capable of performing mechanical movement is an important and urgent problem of modern chemistry. There is growing interest in molecular switches and other devices of molecular electronics based on transition metal complexes; therefore choice of suitable stable organometallic unit is of great importance. An example of such unit is bis(dicarbollide) complexes of transition metals [3,3’-M(1,2-C₂B₉H₁₁)₂]ⁿ⁻. The control on the ligand rotation in such complexes can be reached by introducing substituents which could provide stabilization of certain rotamers due to specific interactions between the ligands, on the one hand, and which can participate as Lewis bases in complex formation with external metals resulting in a change in the rotation angle of the ligands, on the other hand. A series of isomeric methyl sulfide derivatives of cobalt bis(dicarbollide) complexes containing methyl sulfide substituents at boron atoms in different positions of the pentagonal face of the dicarbollide ligands [8,8’-(MeS)₂-3,3’-Co(1,2-C₂B₉H₁₀)₂]⁻, rac-[4,4’-(MeS)₂-3,3’-Co(1,2-C₂B₉H₁₀)₂]⁻ and meso-[4,7’-(MeS)₂-3,3’-Co(1,2-C₂B₉H₁₀)₂]⁻ were synthesized by the reaction of CoCl₂ with the corresponding methyl sulfide carborane derivatives [10-MeS-7,8-C₂B₉H₁₁)₂]⁻ and [10-MeS-7,8-C₂B₉H₁₁)₂]⁻. In the case of asymmetrically substituted cobalt bis(dicarbollide) complexes the corresponding rac- and meso-isomers were successfully separated by column chromatography as the tetrabutylammonium salts. The compounds obtained were studied by the methods of ¹H, ¹³C, and ¹¹B NMR spectroscopy, single crystal X-ray diffraction, cyclic voltammetry, controlled potential coulometry and quantum chemical calculations. It was found that in the solid state, the transoid- and gauche-conformations of the 8,8’- and 4,4’-isomers are stabilized by four intramolecular CH···S(Me)B hydrogen bonds each one (2.683-2.712 Å and 2.709-2.752 Å, respectively), whereas gauche-conformation of the 4,7’-isomer is stabilized by two intramolecular CH···S hydrogen bonds (2.699-2.711 Å). The existence of the intramolecular CH·S(Me)B hydrogen bonding in solutions was supported by the 1H NMR spectroscopy. These data are in a good agreement with results of the quantum chemical calculations. The corresponding iron and nickel complexes were synthesized as well. The reaction of the methyl sulfide derivatives of cobalt bis(dicarbollide) with various labile transition metal complexes results in rupture of intramolecular hydrogen bonds and complexation of the methyl sulfide groups with external metal. This results in stabilization of other rotational conformation of cobalt bis(dicarbollide) and can be used in design of molecular switches. This work was supported by the Russian Science Foundation (16-13-10331).

Keywords: molecular switches, NMR spectroscopy, single crystal X-ray diffraction, transition metal bis(dicarbollide) complexes, quantum chemical calculations

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Authors: Richard Levy, Peter Dawson

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Ft. Conger, located in the Canadian Arctic was one of the most remote 19th-century scientific stations. Established in 1881 on Ellesmere Island, a wood framed structure established a permanent base from which to conduct scientific research. Under the charge of Lt. Greely, Ft. Conger was one of 14 expeditions conducted during the First International Polar Year (FIPY). Our research project “From Science to Survival: Using Virtual Exhibits to Communicate the Significance of Polar Heritage Sites in the Canadian Arctic” focused on the creation of a virtual museum website dedicated to one of the most important polar heritage site in the Canadian Arctic. This website was developed under a grant from Virtual Museum of Canada and enables visitors to explore the fort’s site from 1875 to the present, http://fortconger.org. Heritage sites are often viewed as static places. A goal of this project was to present the change that occurred over time as each new group of explorers adapted the site to their needs. The site was first visited by British explorer George Nares in 1875 – 76. Only later did the United States government select this site for the Lady Franklin Bay Expedition (1881-84) with research to be conducted under the FIPY (1882 – 83). Still later Robert Peary and Matthew Henson attempted to reach the North Pole from Ft. Conger in 1899, 1905 and 1908. A central focus of this research is on the virtual reconstruction of the Ft. Conger. In the summer of 2010, a Zoller+Fröhlich Imager 5006i and Minolta Vivid 910 laser scanner were used to scan terrain and artifacts. Once the scanning was completed, the point clouds were registered and edited to form the basis of a virtual reconstruction. A goal of this project has been to allow visitors to step back in time and explore the interior of these buildings with all of its artifacts. Links to text, historic documents, animations, panorama images, computer games and virtual labs provide explanations of how science was conducted during the 19th century. A major feature of this virtual world is the timeline. Visitors to the website can begin to explore the site when George Nares, in his ship the HMS Discovery, appeared in the harbor in 1875. With the emergence of Lt Greely’s expedition in 1881, we can track the progress made in establishing a scientific outpost. Still later in 1901, with Peary’s presence, the site is transformed again, with the huts having been built from materials salvaged from Greely’s main building. Still later in 2010, we can visit the site during its present state of deterioration and learn about the laser scanning technology which was used to document the site. The Science and Survival at Fort Conger project represents one of the first attempts to use virtual worlds to communicate the historical and scientific significance of polar heritage sites where opportunities for first-hand visitor experiences are not possible because of remote location.

Keywords: 3D imaging, multimedia, virtual reality, arctic

Procedia PDF Downloads 389

Authors: Till Fehlauer, Blanche Collin, Bernard Angeletti, Andrea Somogyi, Claire Lallemand, Perrine Chaurand, Cédric Dentant, Clement Levard, Jerome Rose

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Over the last decades, yttrium (Y) has gained importance in high-tech applications. It is an essential part of alloys and compounds used for lasers, displays, or cell phones, for example. Due to its chemical similarities with the lanthanides, Y is often considered a rare earth element (REE). Despite their increased usage, the environmental behavior of REEs remains poorly understood. Especially regarding their interactions with plants, many uncertainties exist. On the one hand, Y is known to have a negative effect on root development and germination, but on the other hand, it appears to promote plant growth at low concentrations. In order to understand these phenomena, a precise knowledge is necessary about how Y is absorbed by the plant and how it is handled once inside the organism. Contradictory studies exist, stating that due to a similar ionic radius, Y and the other REEs might be absorbed through Ca²⁺-channels, while others suspect that Y has a shared pathway with Al³⁺. In this study, laser ablation coupled ICP-MS, and synchrotron-based micro-X-ray fluorescence (µXRF, beamline Nanoscopium, SOLEIL, France) have been used in order to localize Y within the plant tissue and identify associated elements. The plant used in this study is Saxifraga paniculata, a rugged alpine plant that has shown an affinity for Y in previous studies (in prep.). Furthermore, Saxifraga paniculata performs guttation, which means that it possesses phloem sap secreting openings on the leaf surface that serve to regulate root pressure. These so-called hydathodes could provide special insights in elemental transport in plants. The plants have been grown on Y doped soil (500mg/kg DW) for four months. The results showed that Y was mainly concentrated in the roots of Saxifraga paniculata (260 ± 85mg/kg), and only a small amount was translocated to the leaves (10 ± 7.8mg/kg). µXRF analysis indicated that within the root transects, the majority of Y remained in the epidermis and hardly penetrated the stele. Laser ablation coupled ICP-MS confirmed this finding and showed a positive correlation in the roots between Y, Fe, Al, and to a lesser extent Ca. In the stem transect, Y was mainly detected in a hotspot of approximately 40µm in diameter situated in the endodermis area. Within the stem and especially in the hotspot, Y was highly colocalized with Al and Fe. Similar-sized Y hotspots have been detected in/on the leaves. All of them were strongly colocalized with Al and Fe, except for those situated within the hydathodes, which showed no colocalization with any of the measured elements. Accordingly, a relation between Y and Ca during root uptake remains possible, whereas a correlation to Fe and Al appears to be dominant in the aerial parts, suggesting common storage compartments, the formation of complexes, or a shared pathway during translocation.

Keywords: laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), Phytoaccumulation, Rare earth elements, Saxifraga paniculata, Synchrotron-based micro-X-ray fluorescence, Yttrium

Procedia PDF Downloads 122

Authors: Charlotte K. Lee, Henrique R. N. Aguiar, Ralph Smith, James Baldock, Sam Botchey

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Background: Femoral neck stress fractures (FNSF) are uncommon, making up 1 to 7.2% of stress fractures in healthy subjects. FNSFs are prevalent in young women, military recruits, endurance athletes, and individuals with energy deficiency syndrome or female athlete triad. Presentation is often non-specific and is often misdiagnosed following the initial examination. There is limited research addressing the return–to–activity time after FNSF. Previous studies have demonstrated prognostic time predictions based on various imaging techniques. Here, (1) OxSport clinic FNSF practice standards are retrospectively reviewed, (2) FNSF cohort demographics are examined, (3) Regression models were used to predict return–to–activity prognosis and consequently determine bone stress risk factors. Methods: Patients with a diagnosis of FNSF attending Oxsport clinic between 01/06/2020 and 01/01/2020 were selected from the Rheumatology Assessment Database Innovation in Oxford (RhADiOn) and OxSport Stress Fracture Database (n = 14). (1) Clinical practice was audited against five criteria based on local and National Institute for Health Care Excellence guidance, with a 100% standard. (2) Demographics of the FNSF cohort were examined with Student’s T-Test. (3) Lastly, linear regression and Random Forest regression models were used on this patient cohort to predict return–to–activity time. Consequently, an analysis of feature importance was conducted after fitting each model. Results: OxSport clinical practice met standard (100%) in 3/5 criteria. The criteria not met were patient waiting times and documentation of all bone stress risk factors. Importantly, analysis of patient demographics showed that of the population with complete bone stress risk factor assessments, 53% were positive for modifiable bone stress risk factors. Lastly, linear regression analysis was utilized to identify demographic factors that predicted return–to–activity time [R2 = 79.172%; average error 0.226]. This analysis identified four key variables that predicted return-to-activity time: vitamin D level, total hip DEXA T value, femoral neck DEXA T value, and history of an eating disorder/disordered eating. Furthermore, random forest regression models were employed for this task [R2 = 97.805%; average error 0.024]. Analysis of the importance of each feature again identified a set of 4 variables, 3 of which matched with the linear regression analysis (vitamin D level, total hip DEXA T value, and femoral neck DEXA T value) and the fourth: age. Conclusion: OxSport clinical practice could be improved by more comprehensively evaluating bone stress risk factors. The importance of this evaluation is demonstrated by the population found positive for these risk factors. Using this cohort, potential bone stress risk factors that significantly impacted return-to-activity prognosis were predicted using regression models.

Keywords: eating disorder, bone stress risk factor, femoral neck stress fracture, vitamin D

Procedia PDF Downloads 155

Authors: komal verma, V. S. Moholkar

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In this current study, the challenge of effectively treating and mineralizing industrial wastewater prior to its discharge into natural water bodies, such as rivers and lakes, is being addressed. Particularly, the focus is on the wastewater produced by chemical process industries, including refineries, petrochemicals, fertilizer, pharmaceuticals, pesticides, and dyestuff industries. These wastewaters often contain stubborn organic pollutants that conventional techniques, such as microbial processes cannot efficiently degrade. To tackle this issue, a ternary hybrid technique comprising of adsorption, heterogeneous Fenton process, and sonication has been employed. The study aims to evaluate the effectiveness of this approach for treating and mineralizing wastewater from a fertilizer industry located in Northeast India. The study comprises several key components, starting with the synthesis of the Fe3O4@AC nanocomposite using the co-precipitation method. The nanocomposite is then subjected to comprehensive characterization through various standard techniques, including FTIR, FE-SEM, EDX, TEM, BET surface area analysis, XRD, and magnetic property determination using VSM. Next, the process parameters of wastewater treatment are statistically optimized, focusing on achieving a high level of COD (Chemical Oxygen Demand) removal as the response variable. The Fe3O4@AC nanocomposite's adsorption characteristics and kinetics are also assessed in detail. The remarkable outcome of this study is the successful application of the ternary hybrid technique, combining adsorption, Fenton process, and sonication. This approach proves highly effective, leading to nearly complete mineralization (or TOC removal) of the fertilizer industry wastewater. The results highlight the potential of the Fe3O4@AC nanocomposite and the ternary hybrid technique as a promising solution for tackling challenging wastewater pollutants from various chemical process industries. This paper reports investigations in the mineralization of industrial wastewater (COD = 3246 mg/L, TOC = 2500 mg/L) using a ternary (ultrasound + Fenton + adsorption) hybrid advanced oxidation process. Fe3O4 decorated activated charcoal (Fe3O4@AC) nanocomposites (surface area = 538.88 m2/g; adsorption capacity = 294.31 mg/g) were synthesized using co-precipitation. The wastewater treatment process was optimized using central composite statistical design. At optimum conditions, viz. pH = 4.2, H2O2 loading = 0.71 M, adsorbent dose = 0.34 g/L, reduction in COD and TOC of wastewater were 94.75% and 89%, respectively. This result results from synergistic interactions among the adsorption of pollutants onto activated charcoal and surface Fenton reactions induced due to the leaching of Fe2+/Fe3+ ions from the Fe3O4 nanoparticles. Micro-convection generated due to sonication assisted faster mass transport (adsorption/desorption) of pollutants between Fe3O4@AC nanocomposite and the solution. The net result of this synergism was high interactions and reactions among and radicals and pollutants that resulted in the effective mineralization of wastewater. The Fe3O4@AC showed excellent recovery (> 90 wt%) and reusability (> 90% COD removal) in 5 successive cycles of treatment. LC-MS analysis revealed effective (> 50%) degradation of more than 25 significant contaminants (in the form of herbicides and pesticides) after the treatment with ternary hybrid AOP. Similarly, the toxicity analysis test using the seed germination technique revealed ~ 60% reduction in the toxicity of the wastewater after treatment.

Keywords: chemical oxygen demand (cod), fe3o4@ac nanocomposite, kinetics, lc-ms, rsm, toxicity

Procedia PDF Downloads 37

Authors: Riadh Zorgati, Thomas Triboulet

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In quite diverse application areas such as astronomy, medical imaging, geophysics or nondestructive evaluation, many problems related to calibration, fitting or estimation of a large number of input parameters of a model from a small amount of output noisy data, can be cast as inverse problems. Due to noisy data corruption, insufficient data and model errors, most inverse problems are ill-posed in a Hadamard sense, i.e. existence, uniqueness and stability of the solution are not guaranteed. A wide class of inverse problems in physics relates to the Fredholm equation of the first kind. The ill-posedness of such inverse problem results, after discretization, in a very ill-conditioned linear system of equations, the condition number of the associated matrix can typically range from 109 to 1018. This condition number plays the role of an amplifier of uncertainties on data during inversion and then, renders the inverse problem difficult to handle numerically. Similar problems appear in other areas such as numerical optimization when using interior points algorithms for solving linear programs leads to face ill-conditioned systems of linear equations. Devising efficient solution approaches for such system of equations is therefore of great practical interest. Efficient iterative algorithms are proposed for solving a system of linear equations. The approach is based on a preconditioning of the initial matrix of the system with an approximation of a generalized inverse leading to a stochastic preconditioned matrix. This approach, valid for non-negative matrices, is first extended to hermitian, semi-definite positive matrices and then generalized to any complex rectangular matrices. The main results obtained are as follows: 1) We are able to build a generalized inverse of any complex rectangular matrix which satisfies the convergence condition requested in iterative algorithms for solving a system of linear equations. This completes the (short) list of generalized inverse having this property, after Kaczmarz and Cimmino matrices. Theoretical results on both the characterization of the type of generalized inverse obtained and the convergence are derived. 2) Thanks to its properties, this matrix can be efficiently used in different solving schemes as Richardson-Tanabe or preconditioned conjugate gradients. 3) By using Lp norms, we propose generalized Kaczmarz’s type matrices. We also show how Cimmino's matrix can be considered as a particular case consisting in choosing the Euclidian norm in an asymmetrical structure. 4) Regarding numerical results obtained on some pathological well-known test-cases (Hilbert, Nakasaka, …), some of the proposed algorithms are empirically shown to be more efficient on ill-conditioned problems and more robust to error propagation than the known classical techniques we have tested (Gauss, Moore-Penrose inverse, minimum residue, conjugate gradients, Kaczmarz, Cimmino). We end on a very early prospective application of our approach based on stochastic matrices aiming at computing some parameters (such as the extreme values, the mean, the variance, …) of the solution of a linear system prior to its resolution. Such an approach, if it were to be efficient, would be a source of information on the solution of a system of linear equations.

Keywords: conditioning, generalized inverse, linear system, norms, stochastic matrix

Procedia PDF Downloads 106

Authors: C. Virgilio, J. Carlier, P. Campistron, M. Toubal, P. Garnier, L. Broussous, V. Thomy, B. Nongaillard

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Wetting efficiency of microstructures or nanostructures patterned on Si wafers is a real challenge in integrated circuits manufacturing. In fact, bad or non-uniform wetting during wet processes limits chemical reactions and can lead to non-complete etching or cleaning inside the patterns and device defectivity. This issue is more and more important with the transistors size shrinkage and concerns mainly high aspect ratio structures. Deep Trench Isolation (DTI) structures enabling pixels’ isolation in imaging devices are subject to this phenomenon. While low-frequency acoustic reflectometry principle is a well-known method for Non Destructive Test applications, we have recently shown that it is also well suited for nanostructures wetting characterization in a higher frequency range. In this paper, we present a high-frequency acoustic reflectometry characterization of DTI wetting through a confrontation of both experimental and modeling results. The acoustic method proposed is based on the evaluation of the reflection of a longitudinal acoustic wave generated by a 100 µm diameter ZnO piezoelectric transducer sputtered on the silicon wafer backside using MEMS technologies. The transducers have been fabricated to work at 5 GHz corresponding to a wavelength of 1.7 µm in silicon. The DTI studied structures, manufactured on the wafer frontside, are crossing trenches of 200 nm wide and 4 µm deep (aspect ratio of 20) etched into a Si wafer frontside. In that case, the acoustic signal reflection occurs at the bottom and at the top of the DTI enabling its characterization by monitoring the electrical reflection coefficient of the transducer. A Finite Difference Time Domain (FDTD) model has been developed to predict the behavior of the emitted wave. The model shows that the separation of the reflected echoes (top and bottom of the DTI) from different acoustic modes is possible at 5 Ghz. A good correspondence between experimental and theoretical signals is observed. The model enables the identification of the different acoustic modes. The evaluation of DTI wetting is then performed by focusing on the first reflected echo obtained through the reflection at Si bottom interface, where wetting efficiency is crucial. The reflection coefficient is measured with different water / ethanol mixtures (tunable surface tension) deposited on the wafer frontside. Two cases are studied: with and without PFTS hydrophobic treatment. In the untreated surface case, acoustic reflection coefficient values with water show that liquid imbibition is partial. In the treated surface case, the acoustic reflection is total with water (no liquid in DTI). The impalement of the liquid occurs for a specific surface tension but it is still partial for pure ethanol. DTI bottom shape and local pattern collapse of the trenches can explain these incomplete wetting phenomena. This high-frequency acoustic method sensitivity coupled with a FDTD propagative model thus enables the local determination of the wetting state of a liquid on real structures. Partial wetting states for non-hydrophobic surfaces or low surface tension liquids are then detectable with this method.

Keywords: wetting, acoustic reflectometry, gigahertz, semiconductor

Procedia PDF Downloads 301

Authors: Maria Zulema Morquecho Vega, Fabiola CarolinaMiranda Castro, Rafael Verdugo Miranda, Ignacio Yocupicio Villegas, Ana lidia Barron Raygoza, Martin enrique MArquez Cordova, Jose Alberto Duarte Moller

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Background: Anemopsis californica, also called (tame grass) belongs to the Saururaceae family small, green plant. The blade is long and wide. Gives a white flower. The plant population is only found in humid, swampy habitats, it grows where there is water, along the banks of streams and water holes. In the winter, it dries up. The leaves, rhizomes, or roots of this plant have been used to treat a range of diseases. Some of its healing properties are used to treat wounds, cold and flu symptoms, spasmodic cough, infection, pain and inflammation, burns, swollen feet, as well as lung ailments, asthma, circulatory problems (varicose veins), rheumatoid arthritis, purifies blood, helps in urinary and digestive tract diseases, sores and healing, for headache, sore throat, diarrhea, kidney pain. The tea made from the leaves and roots is used to treat uterine cancer, womb cancer, relieves menstrual pain and stops excessive bleeding after childbirth. It is also used as a gynecological treatment for infections, hemorrhoids, candidiasis and vaginitis. Objective: To study the cytotoxicity of gels prepared with silver nanoparticles in AC extract combined with chitosan, collagen and hyaluronic acid as an alternative therapy for skin conditions. Methods: The Ag NPs were synthesized according to the following method. A 0.3 mg/mL solution is prepared in 10 ml of deionized water, adjust to pH 12 with NaOH, stirring is maintained constant magnetic and a temperature of 80 °C. Subsequently, 100 ul of a 0.1 M AgNO3 solution and kept stirring constantly for 15 min. Once the reaction is complete, measurements are performed by UV-Vis. A gel was prepared in a 5% solution of acetic acid with the respective nanoparticles and AC extract of silver in the extract of AC. Chitosan is added until the process begins to occur gel. At that time, collagen will be added in a ratio of 3 to 5 drops, and later, hyaluronic acid in 2% of the total compound formed. Finally, after resting for 24 hours, the cytotoxic effect of the gels was studied. in the presence of highly positive bacteria Staphylococcus aureus and highly negative for Escherichia coli. Cultures will be incubated for 24 hours in the presence of the compound and compared with the reference. Results: Silver nanoparticles obtained had a spherical shape and sizes among 20 and 30 nm. UV-Vis spectra confirm the presence of silver nanoparticles showing a surface plasmon around 420 nm. Finally, the test in presence of bacteria yield a good antibacterial property of this nanocompound and tests in people were successful. Conclusion: Gel prepared by biogenic synthesis shown beneficious effects in severe acne, acne vulgaris and wound healing with diabetic patients.

Keywords: anemopsis californica, nanomedicina, biotechnology, biomedicine

Procedia PDF Downloads 63

Authors: G. Cunningham, E. Cantor, X. Wu, F. Shen, G. Jiang, S. Philips, C. Bales, Y. Xiao, T. R. Cummins, J. C. Fehrenbacher, B. P. Schneider

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Background: Taxane-induced peripheral neuropathy (TIPN) is the most devastating survivorship issue for patients receiving therapy. Dose reductions due to TIPN in the curative setting lead to inferior outcomes for African American patients, as prior research has shown that this group is more susceptible to developing severe neuropathy. The mechanistic underpinnings of TIPN, however, have not been entirely elucidated. While it would be appealing to use primary tissue to study the development of TIPN, procuring nerves from patients is not realistically feasible, as nerve biopsies are painful and may result in permanent damage. Therefore, our laboratory has investigated paclitaxel-induced neuronal morphological and molecular changes using an ex vivo model of human-induced pluripotent stem cell (iPSC)-derived neurons. Methods: iPSCs are undifferentiated and endlessly dividing cells that can be generated from a patient’s somatic cells, such as peripheral blood mononuclear cells (PBMCs). We successfully reprogrammed PBMCs into iPSCs using the Erythroid Progenitor Reprograming Kit (STEMCell Technologiesᵀᴹ); pluripotency was verified by flow cytometry analysis. iPSCs were then induced into neurons using a differentiation protocol that bypasses the neural progenitor stage and uses selected small-molecule modulators of key signaling pathways (SMAD, Notch, FGFR1 inhibition, and Wnt activation). Results: Flow cytometry analysis revealed expression of core pluripotency transcription factors Nanog, Oct3/4 and Sox2 in iPSCs overlaps with commercially purchased pluripotent cell line UCSD064i-20-2. Trilineage differentiation of iPSCs was confirmed with immunofluorescent imaging with germ-layer-specific markers; Sox17 and ExoA2 for ectoderm, Nestin, and Pax6 for mesoderm, and Ncam and Brachyury for endoderm. Sensory neuron markers, β-III tubulin, and Peripherin were applied to stain the cells for the maturity of iPSC-derived neurons. Patch-clamp electrophysiology and calcitonin gene-related peptide (CGRP) release data supported the functionality of the induced neurons and provided insight into the timing for which downstream assays could be performed (week 4 post-induction). We have also performed a cell viability assay and fluorescence-activated cell sorting (FACS) using four cell-surface markers (CD184, CD44, CD15, and CD24) to select a neuronal population. At least 70% of the cells were viable in the isolated neuron population. Conclusion: We have found that these iPSC-derived neurons recapitulate mature neuronal phenotypes and demonstrate functionality. Thus, this represents a patient-derived ex vivo neuronal model to investigate the molecular mechanisms of clinical TIPN.

Keywords: chemotherapy, iPSC-derived neurons, peripheral neuropathy, taxane, paclitaxel

Procedia PDF Downloads 95

Authors: Ana L. M. Pavan, Guilherme Giacomini, Allan F. F. Alves, Marcela De Oliveira, Fernando A. B. Neto, Maria E. D. Rosa, Andre P. Trindade, Diana R. De Pina

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Mammography is a worldwide image modality used to diagnose breast cancer, even in asymptomatic women. Due to its large availability, mammograms can be used to measure breast density and to predict cancer development. Women with increased mammographic density have a four- to sixfold increase in their risk of developing breast cancer. Therefore, studies have been made to accurately quantify mammographic breast density. In clinical routine, radiologists perform image evaluations through BIRADS (Breast Imaging Reporting and Data System) assessment. However, this method has inter and intraindividual variability. An automatic objective method to measure breast density could relieve radiologist’s workload by providing a first aid opinion. However, pectoral muscle is a high density tissue, with similar characteristics of fibroglandular tissues. It is consequently hard to automatically quantify mammographic breast density. Therefore, a pre-processing is needed to segment the pectoral muscle which may erroneously be quantified as fibroglandular tissue. The aim of this work was to develop an automatic algorithm to segment and extract pectoral muscle in digital mammograms. The database consisted of thirty medio-lateral oblique incidence digital mammography from São Paulo Medical School. This study was developed with ethical approval from the authors’ institutions and national review panels under protocol number 3720-2010. An algorithm was developed, in Matlab® platform, for the pre-processing of images. The algorithm uses image processing tools to automatically segment and extract the pectoral muscle of mammograms. Firstly, it was applied thresholding technique to remove non-biological information from image. Then, the Hough transform is applied, to find the limit of the pectoral muscle, followed by active contour method. Seed of active contour is applied in the limit of pectoral muscle found by Hough transform. An experienced radiologist also manually performed the pectoral muscle segmentation. Both methods, manual and automatic, were compared using the Jaccard index and Bland-Altman statistics. The comparison between manual and the developed automatic method presented a Jaccard similarity coefficient greater than 90% for all analyzed images, showing the efficiency and accuracy of segmentation of the proposed method. The Bland-Altman statistics compared both methods in relation to area (mm²) of segmented pectoral muscle. The statistic showed data within the 95% confidence interval, enhancing the accuracy of segmentation compared to the manual method. Thus, the method proved to be accurate and robust, segmenting rapidly and freely from intra and inter-observer variability. It is concluded that the proposed method may be used reliably to segment pectoral muscle in digital mammography in clinical routine. The segmentation of the pectoral muscle is very important for further quantifications of fibroglandular tissue volume present in the breast.

Keywords: active contour, fibroglandular tissue, hough transform, pectoral muscle

Procedia PDF Downloads 321

Authors: Arfanara Najnin, Michael W. Roach, Jr., Dr. Jianhong Cecilia Xia

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The SkyCar Rapid Transit System (SRT) is an innovative intelligent transport system for the sustainable urban transport system. This system will increase the urban area network connectivity and decrease urban area traffic congestion. The SRT system is designed as a suspended Personal Rapid Transit (PRT) system that travels under a guideway 5m above the ground. A driver-less passenger is via pod-cars that hang from slender beams supported by columns that replace existing lamp posts. The beams are setup in a series of interconnecting loops providing non-stop travel from beginning to end to assure journey time. The SRT forward movement is effected by magnetic motors built into the guideway. Passenger stops are at either at line level 5m above the ground or ground level via a spur guideway that curves off the main thoroughfare. The main objective of this paper is to propose an integrated Automated Transit Network (ATN) technology for the future intelligent transport system in the urban built environment. To fulfil the objective a 4D simulated model in the urban built environment has been proposed by using the concept of SRT-ATN system. The methodology for the design, construction and testing parameters of a Technology Demonstrator (TD) for proof of concept and a Simulator (S) has been demonstrated. The completed TD and S will provide an excellent proving ground for the next development stage, the SRT Prototype (PT) and Pilot System (PS). This paper covered by a 4D simulated model in the virtual built environment is to effectively show how the SRT-ATN system works. OpenSim software has been used to develop the model in a virtual environment, and the scenario has been simulated to understand and visualize the proposed SkyCar Rapid Transit Network model. The SkyCar system will be fabricated in a modular form which is easily transported. The system would be installed in increasingly congested city centers throughout the world, as well as in airports, tourist resorts, race tracks and other special purpose for the urban community. This paper shares the lessons learnt from the proposed innovation and provides recommendations on how to improve the future transport system in urban built environment. Safety and security of passengers are prime factors to be considered for this transit system. Design requirements to meet the safety needs to be part of the research and development phase of the project. Operational safety aspects would also be developed during this period. The vehicles, the track and beam systems and stations are the main components that need to be examined in detail for safety and security of patrons. Measures will also be required to protect columns adjoining intersections from errant vehicles in vehicular traffic collisions. The SkyCar Rapid Transit takes advantage of all current disruptive technologies; batteries, sensors and 4G/5G communication and solar energy technologies which will continue to reduce the costs and make the systems more profitable. SkyCar's energy consumption is extremely low compared to other transport systems.

Keywords: SkyCar, rapid transit, Intelligent Transport System (ITS), Automated Transit Network (ATN), urban built environment, 4D Visualization, smart city

Procedia PDF Downloads 185

Authors: Ahmad Kayvani Fard, Yehia Manawi

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Qatar’s primary source of fresh water is through seawater desalination. Amongst the major processes that are commercially available on the market, the most common large scale techniques are Multi-Stage Flash distillation (MSF), Multi Effect distillation (MED), and Reverse Osmosis (RO). Although commonly used, these three processes are highly expensive down to high energy input requirements and high operating costs allied with maintenance and stress induced on the systems in harsh alkaline media. Beside that cost, environmental footprint of these desalination techniques are significant; from damaging marine eco-system, to huge land use, to discharge of tons of GHG and huge carbon footprint. Other less energy consuming techniques based on membrane separation are being sought to reduce both the carbon footprint and operating costs is membrane distillation (MD). Emerged in 1960s, MD is an alternative technology for water desalination attracting more attention since 1980s. MD process involves the evaporation of a hot feed, typically below boiling point of brine at standard conditions, by creating a water vapor pressure difference across the porous, hydrophobic membrane. Main advantages of MD compared to other commercially available technologies (MSF and MED) and specially RO are reduction of membrane and module stress due to absence of trans-membrane pressure, less impact of contaminant fouling on distillate due to transfer of only water vapor, utilization of low grade or waste heat from oil and gas industries to heat up the feed up to required temperature difference across the membrane, superior water quality, and relatively lower capital and operating cost. To achieve the objective of this study, state of the art flat-sheet cross-flow DCMD bench scale unit was designed, commissioned, and tested. The objective of this study is to analyze the characteristics and morphology of the membrane suitable for DCMD through SEM imaging and contact angle measurement and to study the water quality of distillate produced by DCMD bench scale unit. Comparison with available literature data is undertaken where appropriate and laboratory data is used to compare a DCMD distillate quality with that of other desalination techniques and standards. Membrane SEM analysis showed that the PTFE membrane used for the study has contact angle of 127º with highly porous surface supported with less porous and bigger pore size PP membrane. Study on the effect of feed solution (salinity) and temperature on water quality of distillate produced from ICP and IC analysis showed that with any salinity and different feed temperature (up to 70ºC) the electric conductivity of distillate is less than 5 μS/cm with 99.99% salt rejection and proved to be feasible and effective process capable of consistently producing high quality distillate from very high feed salinity solution (i.e. 100000 mg/L TDS) even with substantial quality difference compared to other desalination methods such as RO and MSF.

Keywords: membrane distillation, waste heat, seawater desalination, membrane, freshwater, direct contact membrane distillation

Procedia PDF Downloads 201

Authors: Sergio A. Bernal-Chavez, Sergio Alcalá-Alcalá, Doris A. Cerecedo-Mercado, Adriana Ganem-Rondero

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The prevalence of people with chronic wounds has increased dramatically by many factors including smoking, obesity and chronic diseases, such as diabetes, that can slow the healing process and increase the risk of becoming chronic. Because of this situation, the improvement of chronic wound treatments is a necessity, which has led to the scientific community to focus on improving the effectiveness of current therapies and the development of new treatments. The wound formation is a physiological complex process, which is characterized by an inflammatory stage with the presence of proinflammatory cells that create a proteolytic microenvironment during the healing process, which includes the degradation of important growth factors and cytokines. This decrease of growth factors and cytokines provides an interesting strategy for wound healing if they are administered externally. The use of nanometric drug delivery systems, such as polymer nanoparticles (NP), also offers an interesting alternative around dermal systems. An interesting strategy would be to propose a formulation based on a thermosensitive hydrogel loaded with polymeric nanoparticles that allows the inclusion and application of a platelet lysate (PL) on damaged skin, with the aim of promoting wound healing. In this work, NP were prepared by a double emulsion-solvent evaporation technique, using polylactic-co-glycolic acid (PLGA) as biodegradable polymer. Firstly, an aqueous solution of PL was emulsified into a PLGA organic solution, previously prepared in dichloromethane (DCM). Then, this disperse system (W/O) was poured into a polyvinyl alcohol (PVA) solution to get the double emulsion (W/O/W), finally the DCM was evaporated by magnetic stirring resulting in the NP formation containing PL. Once the NP were obtained, these systems were characterized by morphology, particle size, Z-potential, encapsulation efficiency (%EE), physical stability, infrared spectrum, calorimetric studies (DSC) and in vitro release profile. The optimized nanoparticles were included in a thermosensitive gel formulation of Pluronic® F-127. The gel was prepared by the cold method at 4 °C and 20% of polymer concentration. Viscosity, sol-gel phase transition, time of no flow solid-gel at wound temperature, changes in particle size by temperature-effect using dynamic light scattering (DLS), occlusive effect, gel degradation, infrared spectrum and micellar point by DSC were evaluated in all gel formulations. PLGA NP of 267 ± 10.5 nm and Z-potential of -29.1 ± 1 mV were obtained. TEM micrographs verified the size of NP and evidenced their spherical shape. The %EE for the system was around 99%. Thermograms and in infrared spectra mark the presence of PL in NP. The systems did not show significant changes in the parameters mentioned above, during the stability studies. Regarding the gel formulation, the transition sol-gel occurred at 28 °C with a time of no flow solid-gel of 7 min at 33°C (common wound temperature). Calorimetric, DLS and infrared studies corroborated the physical properties of a thermosensitive gel, such as the micellar point. In conclusion, the thermosensitive gel described in this work, contains therapeutic amounts of PL and fulfills the technological properties to be used in damaged skin, with potential application in wound healing and tissue regeneration.

Keywords: growth factors, polymeric nanoparticles, thermosensitive hydrogels, tissue regeneration

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Authors: S. S. Kharintsev, E. A. Chernykh, S. K. Saikin, A. I. Fishman, S. G. Kazarian

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Recent advances in improving information storage performance are inseparably linked with circumvention of fundamental constraints such as the supermagnetic limit in heat assisted magnetic recording, charge loss tolerance in solid-state memory and the Abbe’s diffraction limit in optical storage. A substantial breakthrough in the development of nonvolatile storage devices with dimensional scaling has been achieved due to phase-change chalcogenide memory, which nowadays, meets the market needs to the greatest advantage. A further progress is aimed at the development of versatile nonvolatile high-speed memory combining potentials of random access memory and archive storage. The well-established properties of light at the nanoscale empower us to use them for recording optical information with ultrahigh density scaled down to a single molecule, which is the size of a pit. Indeed, diffraction-limited optics is able to record as much information as ~1 Gb/in2. Nonlinear optical effects, for example, two-photon fluorescence recording, allows one to decrease the extent of the pit even more, which results in the recording density up to ~100 Gb/in2. Going beyond the diffraction limit, due to the sub-wavelength confinement of light, pushes the pit size down to a single chromophore, which is, on average, of ~1 nm in length. Thus, the memory capacity can be increased up to the theoretical limit of 1 Pb/in2. Moreover, the field confinement provides faster recording and readout operations due to the enhanced light-matter interaction. This, in turn, leads to the miniaturization of optical devices and the decrease of energy supply down to ~1 μW/cm². Intrinsic features of light such as multimode, mixed polarization and angular momentum in addition to the underlying optical and holographic tools for writing/reading, enriches the storage and encryption of optical information. In particular, the finite extent of the near-field penetration, falling into a range of 50-100 nm, gives the possibility to perform 3D volume (layer-to-layer) recording/readout of optical information. In this study, we demonstrate a comprehensive evidence of isotropic-to-homeotropic phase transition of the azobenzene-functionalized polymer thin film exposed to light and dc electric field using near-field optical microscopy and scanning capacitance microscopy. We unravel a near-field Raman dichroism of a sub-10 nm thick epoxy-based side-chain azo-polymer films with polarization-controlled tip-enhanced Raman scattering. In our study, orientation of azo-chromophores is controlled with a bias voltage gold tip rather than light polarization. Isotropic in-plane and homeotropic out-of-plane arrangement of azo-chromophores in glassy environment can be distinguished with transverse and longitudinal optical near-fields. We demonstrate that both phases are unambiguously visualized by 2D mapping their local dielectric properties with scanning capacity microscopy. The stability of the polar homeotropic phase is strongly sensitive to the thickness of the thin film. We make an analysis of α-transition of the azo-polymer by detecting a temperature-dependent phase jump of an AFM cantilever when passing through the glass temperature. Overall, we anticipate further improvements in optical storage performance, which approaches to a single molecule level.

Keywords: optical memory, azo-dye, near-field, tip-enhanced Raman scattering

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Authors: Diane Ghanem, Arjun Gupta, Rohan Vijayan, Ali Uneri, Babar Shafiq

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Introduction: Ankle sprains and fractures often result in syndesmosis injuries. Unstable syndesmotic injuries result from relative motion between the distal ends of the tibia and fibula, anatomic juncture which should otherwise be rigid, and warrant operative management. Clinical and radiological evaluations of intraoperative syndesmosis stability remain a challenging task as traditional 2D fluoroscopy is limited to a uniplanar translational displacement. The purpose of this pilot cadaveric study is to compare the 2D fluoroscopy and 3D cone beam computed tomography (CBCT) stress-induced syndesmosis displacements. Methods: Three fresh-frozen lower legs underwent 2D fluoroscopy and 3D CIOS CBCT to measure syndesmosis position before dissection. Syndesmotic injury was simulated by resecting the (1) anterior inferior tibiofibular ligament (AITFL), the (2) posterior inferior tibiofibular ligament (PITFL) and the inferior transverse ligament (ITL) simultaneously, followed by the (3) interosseous membrane (IOM). Manual external rotation and Cotton stress test were performed after each of the three resections and 2D and 3D images were acquired. Relevant 2D and 3D parameters included the tibiofibular overlap (TFO), tibiofibular clear space (TCS), relative rotation of the fibula, and anterior-posterior (AP) and medial-lateral (ML) translations of the fibula relative to the tibia. Parameters were measured by two independent observers. Inter-rater reliability was assessed by intraclass correlation coefficient (ICC) to determine measurement precision. Results: Significant mismatches were found in the trends between the 2D and 3D measurements when assessing for TFO, TCS and AP translation across the different resection states. Using 3D CBCT, TFO was inversely proportional to the number of resected ligaments while TCS was directly proportional to the latter across all cadavers and ‘resection + stress’ states. Using 2D fluoroscopy, this trend was not respected under the Cotton stress test. 3D AP translation did not show a reliable trend whereas 2D AP translation of the fibula was positive under the Cotton stress test and negative under the external rotation. 3D relative rotation of the fibula, assessed using the Tang et al. ratio method and Beisemann et al. angular method, suggested slight overall internal rotation with complete resection of the ligaments, with a change < 2mm - threshold which corresponds to the commonly used buffer to account for physiologic laxity as per clinical judgment of the surgeon. Excellent agreement (>0.90) was found between the two independent observers for each of the parameters in both 2D and 3D (overall ICC 0.9968, 95% CI 0.995 - 0.999). Conclusions: The 3D CIOS CBCT appears to reliably depict the trend in TFO and TCS. This might be due to the additional detection of relevant rotational malpositions of the fibula in comparison to the standard 2D fluoroscopy which is limited to a single plane translation. A better understanding of 3D imaging may help surgeons identify the precise measurements planes needed to achieve better syndesmosis repair.

Keywords: 2D fluoroscopy, 3D computed tomography, image processing, syndesmosis injury

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Authors: Jatinder Pal Singh, Harpreet Singh, Gagandeep Singh Digra, Mandeep Kaur Sidhu, Pawan Kumar

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Introduction: Ganglion cyst is a benign condition in which there is a cystic lesion in relation to a joint or a tendon sheath arising from myxoid degeneration of fibrous connective tissue. These can be unilocular or multilocular. In rare cases, there may be multiple ganglion cysts, known as cystic ganglionosis. They can occur at any age but are commonly seen in adults. Clinically they may be asymptomatic or present as swelling or mass effect in adjacent structures. These are common in extremities such as hands and feet. Case Presentation: 11-year-old female child presented with slowly progressive painless swelling of her right hand since the age of 4. Antenatal and perinatal history was unremarkable. Her family history was negative. She denies fever, malaise, morning stiffness, weight loss, fatigue, restriction of joint movements, or any sensory and motor deficit. Lab parameters were negative for inflammatory or infectious etiology. No other joint or extremity involvement was present. On physical examination, the swelling was present on the dorsum and palmer aspect of the right hand and wrist. They were non-tender on palpation without any motor or sensory deficit. MRI hand revealed multiple well-defined fluid signal intensity cystic appearing lesions in periarticular/intraarticular locations in relation to distal radio-ulnar, radio-carpal, intercarpal, carpometacarpal, metacarpophalangeal and interphalangeal joints as well as peritendinous location around flexor tendons more so in the region of wrist, palm, 1st and 5th digit and along extensor tendons in the region of wrist, largest one noted along flexor pollicis longus tendon in thenar region and along 1st digit measuring approx. 4.6 x 1.2 x 1.2 centimeter. Pressure erosions and bone remodelling were noted in the bases of the 2nd to 5th metacarpals, capitate, trapezoid, the distal shaft of 1st metacarpal, and proximal phalanx of 1st digit. Marrow edema was noted in the base and proximal shaft of the 4th metacarpal and proximal shaft of the 3rd metacarpal – likely stress or pressure related. The patient was advised of aspiration, but the family refused the procedure. Therefore the patient was kept on conservative treatment. Conclusion: Cystic ganglionosis is a rare condition with very few cases reported in the medical literature. Its prevalence and association are not known because of the rarity of this condition. It should be considered as an important differential in patients presenting with soft tissue swelling in extremities. Treatment option includes conservative management, aspiration, and surgery. Aspiration has a high recurrence rate. Although surgery has a low recurrence rate, it carries a high rate of complications. Imaging with MRI is essential for confirmation of the cystic nature of lesions and their relation with the joint capsules or tendons. This helps in differentiating from other soft tissue lesions and presurgical planning.

Keywords: radiology, rare, cystic ganglionosis, child

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Authors: Ricardo Alberto Chiong Zevallos, Eduardo Moraes Rego Reis

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Pancreatic adenocarcinoma (PDAC) patients have a less than 10% 5-year survival rate. PDAC has no defined diagnostic and prognostic biomarkers. Gemcitabine is the first-line drug in PDAC and several other cancers. Long non-coding RNAs (lncRNAs) contribute to the tumorigenesis and are potential biomarkers for PDAC. Although lncRNAs aren’t translated into proteins, they have important functions. LncRNAs can decoy or recruit proteins from the epigenetic machinery, act as microRNA sponges, participate in protein translocation through different cellular compartments, and even promote chemoresistance. The chromatin remodeling enzyme EZH2 is a histone methyltransferase that catalyzes the methylation of histone 3 at lysine 27, silencing local expression. EZH2 is ambivalent, it can also activate gene expression independently of its histone methyltransferase activity. EZH2 is overexpressed in several cancers and interacts with lncRNAs, being recruited to a specific locus. EZH2 can be recruited to activate an oncogene or silence a tumor suppressor. The lncRNAs misregulation in cancer can result in the differential recruitment of EZH2 and in a distinct epigenetic landscape, promoting chemoresistance. The relevance of the EZH2-lncRNAs interaction to chemoresistant PDAC was assessed by Real Time quantitative PCR (RT-qPCR) and RNA Immunoprecipitation (RIP) experiments with naïve and gemcitabine-resistant PDAC cells. The expression of several lncRNAs and EZH2 gene targets was evaluated contrasting naïve and resistant cells. Selection of candidate genes was made by bioinformatic analysis and literature curation. Indeed, the resistant cell line showed higher expression of chemoresistant-associated lncRNAs and protein coding genes. RIP detected lncRNAs interacting with EZH2 with varying intensity levels in the cell lines. During RIP, the nuclear fraction of the cells was incubated with an antibody for EZH2 and with magnetic beads. The RNA precipitated with the beads-antibody-EZH2 complex was isolated and reverse transcribed. The presence of candidate lncRNAs was detected by RT-qPCR, and the enrichment was calculated relative to INPUT (total lysate control sample collected before RIP). The enrichment levels varied across the several lncRNAs and cell lines. The EZH2-lncRNA interaction might be responsible for the regulation of chemoresistance-associated genes in multiple cancers. The relevance of the lncRNA-EZH2 interaction to PDAC was assessed by siRNA knockdown of a lncRNA, followed by the analysis of the EZH2 target expression by RT-qPCR. The chromatin immunoprecipitation (ChIP) of EZH2 and H3K27me3 followed by RT-qPCR with primers for EZH2 targets also assess the specificity of the EZH2 recruitment by the lncRNA. This is the first report of the interaction of EZH2 and lncRNAs HOTTIP and PVT1 in chemoresistant PDAC. HOTTIP and PVT1 were described as promoting chemoresistance in several cancers, but the role of EZH2 is not clarified. For the first time, the lncRNA LINC01133 was detected in a chemoresistant cancer. The interaction of EZH2 with LINC02577, LINC00920, LINC00941, and LINC01559 have never been reported in any context. The novel lncRNAs-EZH2 interactions regulate chemoresistant-associated genes in PDAC and might be relevant to other cancers. Therapies targeting EZH2 alone weren’t successful, and a combinatorial approach also targeting the lncRNAs interacting with it might be key to overcome chemoresistance in several cancers.

Keywords: epigenetics, chemoresistance, long non-coding RNAs, pancreatic cancer, histone modification

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Authors: Yusuf Hesham Mohamed

Abstract:

Introduction: Three-dimensional printing technology includes multiple procedures that fabricate three-dimensional objects through consecutively layering two-dimensional cross-sections on top of each other. 3D bioprinting is a promising field of 3D printing, which fabricates tissues and organs by accurately controlling the proper arrangement of diverse biological components. 3D bioprinting uses software and prints biological materials and their supporting components layer-by-layer on a substrate or in a tissue culture plate to produce complex live tissues and organs. 3D food printing is an emerging field of 3D bioprinting in which the 3D printed products are food products that are cheap, require less effort to produce, and have more desirable traits. The Aim of the Study is the development of an affordable 3D bioprinter by altering a locally made CNC instrument with an open-source platform to suit the 3D bio-printer purposes. Later, we went through applying the prototype in several applications regarding food technology and drug testing, including the organ-On-Chip. Materials and Methods: An off-the-shelf 3D printer was modified by designing and fabricating the syringe unit, which was designed on the basis of the Milli-fluidics system. Sodium alginate and gelatin hydrogels were prepared, followed by leaf cell suspension preparation from narrow sections of Fragaria’s viable leaves. The desired 3D structure was modeled, and 3D printing preparations took place. Cell-free and cell-laden hydrogels were printed at room temperature under sterile conditions. Post printing curing process was performed. The printed structure was further studied. Results: Positive results have been achieved using the altered 3D bioprinter where a 3D hydrogel construct of two layers made of the combination of sodium alginate to gelatin (15%: 0.5%) has been printed. DLP 3D printer was used to design the syringe component with a transparent PLA-Pro resin for the creation of a microfluidics system having two channels altered to the double extruder. The hydrogel extruder’s design was based on peristaltic pumps, which utilized a stepper motor. The design and fabrication were made using DIY-3D printed parts. Hard plastic PLA was the material utilized for printing. SEM was used to carry out the porous 3D construct imaging. Multiple physical and chemical tests were performed in order to ensure that the cell line was suitable for hosting. Fragaria plant was developed by suspending Fragaria’s cells from its leaves using the 3D bioprinter. Conclusion: 3D bioprinting is considered to be an emerging scientific field that can facilitate and improve many scientific tests and studies. Thus, having a 3D bioprinter in labs is considered to be an essential requirement. 3D bioprinters are very expensive; however, the fabrication of a 3D printer into a 3D bioprinter can lower the cost of the bioprinter. The 3D bioprinter implemented made use of peristaltic pumps instead of syringe-based pumps in order to extend the ability to print multiple types of materials and cells.

Keywords: scaffold, eco on chip, 3D bioprinter, DLP printer

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

Abstract:

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

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

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Authors: Haohua Zong, Marios Kotsonis

Abstract:

Plasma synthetic jet actuator (PSJA) is a new concept of zero net mass flow actuator which utilizes pulsed arc/spark discharge to rapidly pressurize gas in a small cavity under constant-volume conditions. The unique combination of high exit jet velocity (>400 m/s) and high actuation frequency (>5 kHz) provides a promising solution for high-speed high-Reynolds-number flow control. This paper focuses on the performance of PSJA in repetitive working mode which is more relevant to future flow control applications. A two-electrodes PSJA (cavity volume: 424 mm3, orifice diameter: 2 mm) together with a capacitive discharge circuit (discharge energy: 50 mJ-110 mJ) is designed to enable repetitive operation. Time-Resolved Particle Imaging Velocimetry (TR-PIV) system working at 10 kHz is exploited to investigate the influence of discharge frequency on performance of PSJA. In total, seven cases are tested, covering a wide range of discharge frequencies (20 Hz-560 Hz). The pertinent flow features (shock wave, vortex ring and jet) remain the same for single shot mode and repetitive working mode. Shock wave is issued prior to jet eruption. Two distinct vortex rings are formed in one cycle. The first one is produced by the starting jet whereas the second one is related with the shock wave reflection in cavity. A sudden pressure rise is induced at the throat inlet by the reflection of primary shock wave, promoting the shedding of second vortex ring. In one cycle, jet exit velocity first increases sharply, then decreases almost linearly. Afterwards, an alternate occurrence of multiple jet stages and refresh stages is observed. By monitoring the dynamic evolution of exit velocity in one cycle, some integral performance parameters of PSJA can be deduced. As frequency increases, the jet intensity in steady phase decreases monotonically. In the investigated frequency range, jet duration time drops from 250 µs to 210 µs and peak jet velocity decreases from 53 m/s to approximately 39 m/s. The jet impulse and the expelled gas mass (0.69 µN∙s and 0.027 mg at 20 Hz) decline by 48% and 40%, respectively. However, the electro-mechanical efficiency of PSJA defined by the ratio of jet mechanical energy to capacitor energy doesn’t show significant difference (o(0.01%)). Fourier transformation of the temporal exit velocity signal indicates two dominant frequencies. One corresponds to the discharge frequency, while the other accounts for the alternation frequency of jet stage and refresh stage in one cycle. The alternation period (300 µs approximately) is independent of discharge frequency, and possibly determined intrinsically by the actuator geometry. A simple analytical model is established to interpret the alternation of jet stage and refresh stage. Results show that the dynamic response of exit velocity to a small-scale disturbance (jump in cavity pressure) can be treated as a second-order under-damping system. Oscillation frequency of the exit velocity, namely alternation frequency, is positively proportional to exit area, but inversely proportional to cavity volume and throat length. Theoretical value of alternation period (305 µs) agrees well with the experimental value.

Keywords: plasma, synthetic jet, actuator, frequency effect

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