Search results for: PAMAM magnetic nanoparticles

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: 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: N. Reza Pour, S. Chuah, T. Vo

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Background: Vertebral artery dissection (VAD) is a rare complication of pregnancy. It can occur spontaneously or following a traumatic event. The pathogenesis is unclear. Predisposing factors include chronic hypertension, Marfan’s syndrome, fibromuscular dysplasia, vasculitis and cystic medial necrosis. Physiological changes of pregnancy have also been proposed as potential mechanisms of injury to the vessel wall. The clinical presentation varies and it can present as a headache, neck pain, diplopia, transient ischaemic attack, or an ischemic stroke. Isolated cases of VAD in pregnancy and puerperium have been reported in the literature. One case was found to have posterior circulation stroke as a result of bilateral VAD and labour was induced at 37 weeks gestation for preeclampsia. Another patient at 38 weeks with severe neck pain that persisted after induction for elevated blood pressure and arteriography showed right VAD postpartum. A single case of lethal VAD in pregnancy with subsequent massive subarachnoid haemorrhage has been reported which was confirmed by the autopsy. Case Presentation: We report two cases of vertebral artery dissection in pregnancy. The first patient was a 32-year-old primigravida presented at the 38th week of pregnancy with the onset of early labour and blood pressure (BP) of 130/70 on arrival. After 2 hours, the patient developed a severe headache with blurry vision and BP was 238/120. Despite treatment with an intravenous antihypertensive, she had eclamptic fit. Magnesium solfate was started and Emergency Caesarean Section was performed under the general anaesthesia. On the second day after the operation, she developed left-sided neck pain. Magnetic Resonance Imaging (MRI) angiography confirmed a short segment left vertebral artery dissection at the level of C3. The patient was treated with aspirin and remained stable without any neurological deficit. The second patient was a 33-year-old primigavida who was admitted to the hospital at 36 weeks gestation with BP of 155/105, constant headache and visual disturbances. She was medicated with an oral antihypertensive agent. On day 4, she complained of right-sided neck pain. MRI angiogram revealed a short segment dissection of the right vertebral artery at the C2-3 level. Pregnancy was terminated on the same day with emergency Caesarean Section and anticoagulation was started subsequently. Post-operative recovery was complicated by rectus sheath haematoma requiring evacuation. She was discharged home on Aspirin without any neurological sequelae. Conclusion: Because of collateral circulation, unilateral vertebral artery dissections may go unrecognized and may be more common than suspected. The outcome for most patients is benign, reflecting the adequacy of the collateral circulation in young patients. Spontaneous VAD is usually treated with anticoagulation or antiplatelet therapy for a minimum of 3-6 months to prevent future ischaemic events, allowing the dissection to heal on its own. We had two cases of VAD in the context of hypertensive disorders of pregnancy with an acceptable outcome. A high level of vigilance is required particularly with preeclamptic patients presenting with head/neck pain to allow an early diagnosis. This is as we hypothesize, early and aggressive management of vertebral artery dissection may potentially prevent further complications.

Keywords: eclampsia, preeclampsia, pregnancy, Vertebral Artery Dissection

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Authors: K. Ghosh, S. N. Tripathi, Manish Joshi, Y. S. Mayya, Arshad Khan, B. K. Sapra

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We have developed a CFD coupled aerosol microphysics model in the context of aerosol generation from a glowing wire. The governing equations can be solved implicitly for mass, momentum, energy transfer along with aerosol dynamics. The computationally efficient framework can simulate temporal behavior of total number concentration and number size distribution. This formulation uniquely couples standard K-Epsilon scheme with boundary layer model with detailed aerosol dynamics through residence time. This model uses measured temperatures (wire surface and axial/radial surroundings) and wire compositional data apart from other usual inputs for simulations. The model predictions show that bulk fluid motion and local heat distribution can significantly affect the aerosol behavior when the buoyancy effect in momentum transfer is considered. Buoyancy generated turbulence was found to be affecting parameters related to aerosol dynamics and transport as well. The model was validated by comparing simulated predictions with results obtained from six controlled experiments performed with a laboratory-made hot wire nanoparticle generator. Condensation particle counter (CPC) and scanning mobility particle sizer (SMPS) were used for measurement of total number concentration and number size distribution at the outlet of reactor cell during these experiments. Our model-predicted results were found to be in reasonable agreement with observed values. The developed model is fast (fully implicit) and numerically stable. It can be used specifically for applications in the context of the behavior of aerosol particles generated from glowing wire technique and in general for other similar large scale domains. Incorporation of CFD in aerosol microphysics framework provides a realistic platform to study natural convection driven systems/ applications. Aerosol dynamics sub-modules (nucleation, coagulation, wall deposition) have been coupled with Navier Stokes equations modified to include buoyancy coupled K-Epsilon turbulence model. Coupled flow-aerosol dynamics equation was solved numerically and in the implicit scheme. Wire composition and temperature (wire surface and cell domain) were obtained/measured, to be used as input for the model simulations. Model simulations showed a significant effect of fluid properties on the dynamics of aerosol particles. The role of buoyancy was highlighted by observation and interpretation of nucleation zones in the planes above the wire axis. The model was validated against measured temporal evolution, total number concentration and size distribution at the outlet of hot wire generator cell. Experimentally averaged and simulated total number concentrations were found to match closely, barring values at initial times. Steady-state number size distribution matched very well for sub 10 nm particle diameters while reasonable differences were noticed for higher size ranges. Although tuned specifically for the present context (i.e., aerosol generation from hotwire generator), the model can also be used for diverse applications, e.g., emission of particles from hot zones (chimneys, exhaust), fires and atmospheric cloud dynamics.

Keywords: nanoparticles, k-epsilon model, buoyancy, CFD, hot wire generator, aerosol dynamics

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Authors: Yury S. Shpanskiy, Boris V. Kuteev

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Development of a fusion-fission hybrid facility based on superconducting conventional tokamak DEMO-FNS runs in Russia since 2013. The main design goal is to reach the technical feasibility and outline prospects of industrial hybrid technologies providing the production of neutrons, fuel nuclides, tritium, high-temperature heat, electricity and subcritical transmutation in Fusion-Fission Hybrid Systems. The facility should operate in a steady-state mode at the fusion power of 40 MW and fission reactions of 400 MW. Major tokamak parameters are the following: major radius R=3.2 m, minor radius a=1.0 m, elongation 2.1, triangularity 0.5. The design provides the neutron wall loading of ~0.2 MW/m², the lifetime neutron fluence of ~2 MWa/m², with the surface area of the active cores and tritium breeding blanket ~100 m². Core plasma modelling showed that the neutron yield ~10¹⁹ n/s is maximal if the tritium/deuterium density ratio is 1.5-2.3. The design of the electromagnetic system (EMS) defined its basic parameters, accounting for the coils strength and stability, and identified the most problematic nodes in the toroidal field coils and the central solenoid. The EMS generates toroidal, poloidal and correcting magnetic fields necessary for the plasma shaping and confinement inside the vacuum vessel. EMC consists of eighteen superconducting toroidal field coils, eight poloidal field coils, five sections of a central solenoid, correction coils, in-vessel coils for vertical plasma control. Supporting structures, the thermal shield, and the cryostat maintain its operation. EMS operates with the pulse duration of up to 5000 hours at the plasma current up to 5 MA. The vacuum vessel (VV) is an all-welded two-layer toroidal shell placed inside the EMS. The free space between the vessel shells is filled with water and boron steel plates, which form the neutron protection of the EMS. The VV-volume is 265 m³, its mass with manifolds is 1800 tons. The nuclear blanket of DEMO-FNS facility was designed to provide functions of minor actinides transmutation, tritium production and enrichment of spent nuclear fuel. The vertical overloading of the subcritical active cores with MA was chosen as prospective. Analysis of the device neutronics and the hybrid blanket thermal-hydraulic characteristics has been performed for the system with functions covering transmutation of minor actinides, production of tritium and enrichment of spent nuclear fuel. A study of FNS facilities role in the Russian closed nuclear fuel cycle was performed. It showed that during ~100 years of operation three FNS facilities with fission power of 3 GW controlled by fusion neutron source with power of 40 MW can burn 98 tons of minor actinides and 198 tons of Pu-239 can be produced for startup loading of 20 fast reactors. Instead of Pu-239, up to 25 kg of tritium per year may be produced for startup of fusion reactors using blocks with lithium orthosilicate instead of fissile breeder blankets.

Keywords: fusion-fission hybrid system, conventional tokamak, superconducting electromagnetic system, two-layer vacuum vessel, subcritical active cores, nuclear fuel cycle

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Authors: Dagmara Malina, Katarzyna Bialik-Wąs, Klaudia Pluta

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The growing significance of transdermal systems, in which skin is a route for systemic drug delivery, has generated a considerable amount of data which has resulted in a deeper understanding of the mechanisms of transport across the skin in the context of the controlled and prolonged release of active substances. One of such solutions may be the use of carrier systems based on intelligent polymers with different physicochemical properties. In these systems, active substances, e.g. drugs, can be conjugated (attached), immobilized, or encapsulated in a polymer matrix that is sensitive to specific environmental conditions (e.g. pH or temperature changes). Intelligent polymers can be divided according to their sensitivity to specific environmental stimuli such as temperature, pH, light, electric, magnetic, sound, or electromagnetic fields. Materials & methods—The first stage of the presented research concerned the synthesis of pH-sensitive polymeric carriers by a radical polymerization reaction. Then, the selected active substance (hydrocortisone) was introduced into polymeric carriers. In a further stage, bio-hybrid sodium alginate/poly(vinyl alcohol) – SA/PVA-based hydrogel matrices modified with various carrier-drug systems were prepared with the chemical cross-linking method. The conducted research included the assessment of physicochemical properties of obtained materials i.e. degree of hydrogel swelling and degradation studies as a function of pH in distilled water and phosphate-buffered saline (PBS) at 37°C in time. The gel fraction represents the insoluble gel fraction as a result of inter-molecule cross-linking formation was also measured. Additionally, the chemical structure of obtained hydrogels was confirmed using FT-IR spectroscopic technique. The dynamic light scattering (DLS) technique was used for the analysis of the average particle size of polymer-carriers and carrier-drug systems. The nanocarriers morphology was observed using SEM microscopy. Results & Discussion—The analysis of the encapsulated polymeric carriers showed that it was possible to obtain the time-stable empty pH-sensitive carrier with an average size 479 nm and the encapsulated system containing hydrocortisone with an average 543 nm, which was introduced into hydrogel structure. Bio-hybrid hydrogel matrices are stable materials, and the presence of an additional component: pH-sensitive carrier – hydrocortisone system, does not reduce the degree of cross-linking of the matrix nor its swelling ability. Moreover, the results of swelling tests indicate that systems containing higher concentrations of the drug have a slightly higher sorption capacity in each of the media used. All analyzed materials show stable and statically changing swelling values in simulated body fluids - there is no sudden fluid uptake and no rapid release from the material. The analysis of FT-IR spectra confirms the chemical structure of the obtained bio-hybrid hydrogel matrices. In the case of modifications with a pH-sensitive carrier, a much more intense band can be observed in the 3200-3500 cm⁻¹ range, which most likely originates from the strong hydrogen interactions that occur between individual components.

Keywords: hydrogels, polymer nanocarriers, sodium alginate/poly(vinyl alcohol) matrices, wound dressings.

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Authors: Alberto Fina, Samuele Colonna, Maria del Mar Bernal, Orietta Monticelli, Mauro Tortello, Renato Gonnelli, Julio Gomez, Chiara Novara, Guido Saracco

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Thermally conductive polymer nanocomposites are of high interest for several applications including low-temperature heat recovery, heat exchangers in a corrosive environment and heat management in electronics and flexible electronics. In this paper, the preparation of thermally conductive nanocomposites exploiting graphene-related materials is addressed, along with their thermal characterization. In particular, correlations between 1- chemical and physical features of the nanoflakes and 2- processing conditions with the heat conduction properties of nanocomposites is studied. Polymers are heat insulators; therefore, the inclusion of conductive particles is the typical solution to obtain a sufficient thermal conductivity. In addition to traditional microparticles such as graphite and ceramics, several nanoparticles have been proposed, including carbon nanotubes and graphene, for the use in polymer nanocomposites. Indeed, thermal conductivities for both carbon nanotubes and graphenes were reported in the wide range of about 1500 to 6000 W/mK, despite such property may decrease dramatically as a function of the size, number of layers, the density of topological defects, re-hybridization defects as well as on the presence of impurities. Different synthetic techniques have been developed, including mechanical cleavage of graphite, epitaxial growth on SiC, chemical vapor deposition, and liquid phase exfoliation. However, the industrial scale-up of graphene, defined as an individual, single-atom-thick sheet of hexagonally arranged sp2-bonded carbons still remains very challenging. For large scale bulk applications in polymer nanocomposites, some graphene-related materials such as multilayer graphenes (MLG), reduced graphene oxide (rGO) or graphite nanoplatelets (GNP) are currently the most interesting graphene-based materials. In this paper, different types of graphene-related materials were characterized for their chemical/physical as well as for thermal properties of individual flakes. Two selected rGOs were annealed at 1700°C in vacuum for 1 h to reduce defectiveness of the carbon structure. Thermal conductivity increase of individual GNP with annealing was assessed via scanning thermal microscopy. Graphene nano papers were prepared from both conventional RGO and annealed RGO flakes. Characterization of the nanopapers evidenced a five-fold increase in the thermal diffusivity on the nano paper plane for annealed nanoflakes, compared to pristine ones, demonstrating the importance of structural defectiveness reduction to maximize the heat dissipation performance. Both pristine and annealed RGO were used to prepare polymer nanocomposites, by melt reactive extrusion. Thermal conductivity showed two- to three-fold increase in the thermal conductivity of the nanocomposite was observed for high temperature treated RGO compared to untreated RGO, evidencing the importance of using low defectivity nanoflakes. Furthermore, the study of different processing paremeters (time, temperature, shear rate) during the preparation of poly (butylene terephthalate) nanocomposites evidenced a clear correlation with the dispersion and fragmentation of the GNP nanoflakes; which in turn affected the thermal conductivity performance. Thermal conductivity of about 1.7 W/mK, i.e. one order of magnitude higher than for pristine polymer, was obtained with 10%wt of annealed GNPs, which is in line with state of the art nanocomposites prepared by more complex and less upscalable in situ polymerization processes.

Keywords: graphene, graphene-related materials, scanning thermal microscopy, thermally conductive polymer nanocomposites

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Authors: Saif Al Ghafri, Thomas Hughes, Armand Karimi, Kumarini Seneviratne, Jordan Oakley, Michael Johns, Eric F. May

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Knowledge of the thermophysical properties of complex mixtures at extreme conditions of pressure and temperature have always been essential to the Liquefied Natural Gas (LNG) industry’s evolution because of the tremendous technical challenges present at all stages in the supply chain from production to liquefaction to transport. Each stage is designed using predictions of the mixture’s properties, such as density, viscosity, surface tension, heat capacity and phase behaviour as a function of temperature, pressure, and composition. Unfortunately, currently available models lead to equipment over-designs of 15% or more. To achieve better designs that work more effectively and/or over a wider range of conditions, new fundamental property data are essential, both to resolve discrepancies in our current predictive capabilities and to extend them to the higher-pressure conditions characteristic of many new gas fields. Furthermore, innovative experimental techniques are required to measure different thermophysical properties at high pressures and over a wide range of temperatures, including near the mixture’s critical points where gas and liquid become indistinguishable and most existing predictive fluid property models used breakdown. In this work, we present a wide range of experimental measurements made for different binary and ternary mixtures relevant to LNG processing, with a particular focus on viscosity, surface tension, heat capacity, bubble-points and density. For this purpose, customized and specialized apparatus were designed and validated over the temperature range (200 to 423) K at pressures to 35 MPa. The mixtures studied were (CH4 + C3H8), (CH4 + C3H8 + CO2) and (CH4 + C3H8 + C7H16); in the last of these the heptane contents was up to 10 mol %. Viscosity was measured using a vibrating wire apparatus, while mixture densities were obtained by means of a high-pressure magnetic-suspension densimeter and an isochoric cell apparatus; the latter was also used to determine bubble-points. Surface tensions were measured using the capillary rise method in a visual cell, which also enabled the location of the mixture critical point to be determined from observations of critical opalescence. Mixture heat capacities were measured using a customised high-pressure differential scanning calorimeter (DSC). The combined standard relative uncertainties were less than 0.3% for density, 2% for viscosity, 3% for heat capacity and 3 % for surface tension. The extensive experimental data gathered in this work were compared with a variety of different advanced engineering models frequently used for predicting thermophysical properties of mixtures relevant to LNG processing. In many cases the discrepancies between the predictions of different engineering models for these mixtures was large, and the high quality data allowed erroneous but often widely-used models to be identified. The data enable the development of new or improved models, to be implemented in process simulation software, so that the fluid properties needed for equipment and process design can be predicted reliably. This in turn will enable reduced capital and operational expenditure by the LNG industry. The current work also aided the community of scientists working to advance theoretical descriptions of fluid properties by allowing to identify deficiencies in theoretical descriptions and calculations.

Keywords: LNG, thermophysical, viscosity, density, surface tension, heat capacity, bubble points, models

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Authors: Glykeria A. Visvini, George Ν. Mathioudakis, Amaia Soto Beobide, George A. Voyiatzis

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Polymer nanocomposites are materials in which a polymer matrix is reinforced with nanoscale inclusions, such as nanoparticles, nanoplates, or nanofibers. These nanoscale inclusions can significantly enhance the mechanical, thermal, electrical, and other properties of the polymer matrix, making them attractive for a wide range of industrial applications. These properties can be tailored by adjusting the type and the concentration of the nanoinclusions, which provides a high degree of flexibility in their design and development. An important property that polymeric membranes can exhibit is water vapor permeability (WVP). This can be accomplished by various methods, including the incorporation of micro/nano-fillers into the polymer matrix. In this way, a micro/nano-pore network can be formed, allowing water vapor to permeate through the membrane. At the same time, the membrane can be stretched uni- or bi-axially, creating aligned or cross-linked micropores in the composite, respectively, which can also increase the WVP. Nowadays, in industry, stretched films reinforced with CaCO3 develop micro-porosity sufficient to give them breathability characteristics. Carbon-based nanomaterials, such as graphene oxide (GO), are tentatively expected to be able to effectively improve the WVP of corresponding composite polymer films. The presence in the GO structure of various functional oxidizing groups enhances its ability to attract and channel water molecules, exploiting the unique large surface area of graphene that allows the rapid transport of water molecules. Polypropylene (PP) is widely used in various industrial applications due to its desirable properties, including good chemical resistance, excellent thermal stability, low cost, and easy processability. The specific properties of PP are highly influenced by its crystalline behavior, which is determined by its processing conditions. The development of the β-crystalline phase in PP, in combination with stretching, is anticipating improving the microporosity of the polymer matrix, thereby enhancing its WVP. The aim of present study is to create breathable PP composite membranes using carbon-based nanomaterials, such as graphene oxide (GO), reduced graphene oxide (rGO), and graphene nanoplatelets (GNPs). Unlike traditional methods that rely on the drawing process to enhance the WVP of PP, this study intents to develop a low-cost approach using melt mixing with β-nucleating agents and carbon fillers to create highly breathable PP composite membranes. The study aims to investigate how the concentration of these additives affects the water vapor transport properties of the resulting PP films/membranes. The presence of β-nucleating agents and carbon fillers is expected to enhance β-phase growth in PP, while an alternation between β- and α-phase is expected to lead to improved microporosity and WVP. Our ambition is to develop highly breathable PP composite films with superior performance and at a lower cost compared to the benchmark. Acknowledgment: This research has been co‐financed by the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call «Special Actions "AQUACULTURE"-"INDUSTRIAL MATERIALS"-"OPEN INNOVATION IN CULTURE"» (project code: Τ6YBP-00337)

Keywords: carbon based nanomaterials, nanocomposites, nucleating agent, polypropylene, water vapor permeability

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

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

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

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Authors: Anita Conti, Riccardo Ossanna, Lindsey A. Quintero, Giamaica Conti, Andrea Sbarbati

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Ischemia/reperfusion (IR) injury induces muscle fiber atrophy and skeletal muscle fiber death with subsequently functionality loss. The heterogeneous pool of cells, especially mesenchymal stem cells, contained in the stromal vascular fraction (SVF) of adipose tissue could promote muscle fiber regeneration. To prevent SVF dispersion, it has been proposed the use of injectable biopolymers that work as cells carrier. A significant element of the extracellular matrix is hyaluronic acid (HA), which has been widely used in regenerative medicine as a cell scaffold given its biocompatibility, degradability, and the possibility of chemical functionalization. Connective tissue micro-fragments enriched with SVF obtained from mechanical disaggregation of adipose tissue were evaluated for IR muscle injury regeneration using low molecular weight HA as a scaffold. IR induction. Hindlimb ischemia was induced in 9 athymic nude mice through the clamping of the right quadriceps using a plastic band. Reperfusion was induced by cutting the plastic band after 3 hours of ischemic period. Contralateral (left) muscular tissue was used as healthy control. Treatment. Twenty-four hours after the IR induction, animals (n=3) were intramuscularly injected with 100 µl of SVF mixed with HA (SVF-HA). Animals treated with 100 µl of HA (n=3) and 100 µl saline solution (n=3) were used as control. Treatment monitoring. All animals were in vivo monitored by magnetic resonance imaging (MRI) at 5, 7, 14 and 18 days post-injury (dpi). High-resolution morphological T2 weighed, quantitative T2 map and Dynamic Contrast-Enhanced (DCE) images were acquired in order to assess the regenerative potential of SVF-HA treatment. Ex vivo evaluation. After 18 days from IR induction, animals were sacrificed, and the muscles were harvested for histological examination. At 5 dpi T2 high-resolution MR images clearly reveal the presence of an extensive edematous area due to IR damage for all groups identifiable as an increase of signal intensity (SI) of muscular and surrounding tissue. At 7 dpi, animals of the SVF-HA group showed a reduction of SI, and the T2relaxation time of muscle tissue of the HA-SVF group was 29±0.5ms, comparable with the T2relaxation time of contralateral muscular tissue (30±0.7ms). These suggest a reduction of edematous overflow and swelling. The T2relaxation time at 7dpi of HA and saline groups were 84±2ms and 90±5ms, respectively, which remained elevated during the rest of the study. The evaluation of vascular regeneration showed similar results. Indeed, DCE-MRI analysis revealed a complete recovery of muscular tissue perfusion after 14 dpi for the SVF-HA group, while for the saline and HA group, controls remained in a damaged state. Finally, the histological examination of SVF-HA treated animals exhibited well-defined and organized fibers morphology with a lateralized nucleus, similar to contralateral healthy muscular tissue. On the contrary, HA and saline-treated animals presented inflammatory infiltrates, with HA slightly improving the diameter of the fibers and less degenerated tissue. Our findings show that connective tissue micro-fragments enriched with SVF induce higher muscle homeostasis and perfusion restoration in contrast to control groups.

Keywords: ischemia/reperfusion injury, regenerative medicine, resonance imaging, stromal vascular fraction

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Authors: Zeyu Zhou, Ziyu Zhao, Xiaochen Yang, Ling AI, Heng Zhai, Stuart Holmes

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As a promising sustainable alternative to traditional fossil fuels, fuel cell technology is highly favoured due to its enhanced working efficiency and reduced emissions. In the context of high-temperature fuel cells (operating above 100 °C), the most commonly used proton exchange membrane (PEM) is the Polybenzimidazole (PBI) doped phosphoric acid (PA) membrane. Grafting is a promising strategy to advance PA-doped PBI PEM technology. The existing grafting modification on PBI PEMs mainly focuses on grafting phosphate-containing or alkaline groups onto the PBI molecular chains. However, quaternary ammonium-based grafting approaches face a common challenge. To initiate the N-alkylation reaction, deacidifying agents such as NaH, NaOH, KOH, K2CO3, etc., can lead to ionic crosslinking between the quaternary ammonium group and PBI. Polyvinylpyrrolidone (PVP) is another widely used polymer, the N-heterocycle groups within PVP endow it with a significant ability to absorb PA. Recently, PVP has attracted substantial attention in the field of fuel cells due to its reduced environmental impact and impressive fuel cell performance. However, due to the the poor compatibility of PVP in PBI, few research apply PVP in PA-doped PBI PEMs. This work introduces an innovative strategy to graft PVP onto PBI to form a network-like polymer. Due to the absence of quaternary ammonium groups, PVP does not pose issues related to crosslinking with PBI. Moreover, the nitrogen-containing functional groups on PVP provide PBI with a robust phosphoric acid retention ability. The nuclear magnetic resonance (NMR) hydrogen spectrum analysis results indicate the successful completion of the grafting reaction where N-alkylation reactions happen on both sides of the grafting agent 1,4-bis(chloromethyl)benzene. On one side, the reaction takes place with the hydrogen atoms on the imidazole groups of PBI, while on the other side, it reacts with the terminal amino group of PVP. The XPS results provide additional evidence from the perspective of the element. On synthesized PBI-g-PVP surfaces, there is an absence of chlorine (chlorine in grafting agent 1,4-bis(chloromethyl)benzene is substituted) element but a presence of sulfur element (sulfur element in terminal amino PVP appears in PBI), which demonstrates the occurrence of the grafting reaction and PVP is successfully grafted onto PBI. Prepare these modified membranes into MEA. It was found that during the fuel cell operation, all the grafted membranes showed substantial improvement in maximum current density and peak power density compared to unmodified one. For PBI-g-PVP 30, with a grafting degree of 22.4%, the peak power density reaches 1312 mW cm⁻², marking a 59.6% enhancement compared to the pristine PBI membrane. The improvement is caused by the improved PA binding ability of the membrane after grafting. The AST test result shows that the grafting membranes have better long-term durability and performance than unmodified membranes attributed to the presence of added PA binding sites, which can effectively prevent the PA leaching caused by proton migration. In conclusion, the test results indicate that grafting PVP onto PBI is a promising strategy which can effectively improve the fuel cell performance.

Keywords: fuel cell, grafting modification, PA doping ability, PVP

Procedia PDF Downloads 78

Authors: Shereen Ismail Fawaz, Shin-Ichi Izumi, Nouran Mohamed Salah, Heba G. Saber, Ibrahim Mohamed Roushdi

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Background: Multiple sclerosis (MS) is a chronic, inflammatory, mainly demyelinating disease of the central nervous system, more common in young adults. Cerebellar involvement is one of the most disabling lesions in MS and is usually a sign of disease progression. It plays a major role in the planning, initiation, and organization of movement via its influence on the motor cortex and corticospinal outputs. Therefore, it contributes to controlling movement, motor adaptation, and motor learning, in addition to its vast connections with other major pathways controlling balance, such as the cerebellopropriospinal pathways and cerebellovestibular pathways. Hence, trying to stimulate the cerebellum by facilitatory protocols will add to our motor control and balance function. Non-invasive brain stimulation, both repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), has recently emerged as effective neuromodulators to influence motor and nonmotor functions of the brain. Anodal tDCS has been shown to improve motor skill learning and motor performance beyond the training period. Similarly, rTMS, when used at high frequency (>5 Hz), has a facilitatory effect on the motor cortex. Objective: Our aim was to determine the effect of high-frequency rTMS over the cerebellum in improving balance and functional ambulation of multiple sclerosis patients with Ataxia. Patients and methods: This was a randomized single-blinded placebo-controlled prospective trial on 40 patients. The active group (N=20) received real rTMS sessions, and the control group (N=20) received Sham rTMS using a placebo program designed for this treatment. Both groups received 12 sessions of high-frequency rTMS over the cerebellum, followed by an intensive exercise training program. Sessions were given three times per week for four weeks. The active group protocol had a frequency of 10 Hz rTMS over the cerebellar vermis, work period 5S, number of trains 25, and intertrain interval 25s. The total number of pulses was 1250 pulses per session. The control group received Sham rTMS using a placebo program designed for this treatment. Both groups of patients received an intensive exercise program, which included generalized strengthening exercises, endurance and aerobic training, trunk abdominal exercises, generalized balance training exercises, and task-oriented training such as Boxing. As a primary outcome measure the Modified ICARS was used. Static Posturography was done with: Patients were tested both with open and closed eyes. Secondary outcome measures included the expanded Disability Status Scale (EDSS) and 8 Meter walk test (8MWT). Results: The active group showed significant improvements in all the functional scales, modified ICARS, EDSS, and 8-meter walk test, in addition to significant differences in static Posturography with open eyes, while the control group did not show such differences. Conclusion: Cerebellar high-frequency rTMS could be effective in the functional improvement of balance in MS patients with ataxia.

Keywords: brain neuromodulation, high frequency rTMS, cerebellar stimulation, multiple sclerosis, balance rehabilitation

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Authors: Amandeep Thakur, Yi-Hsuan Chu, Chun-Hsu Pan, Kunal Nepali

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The transfer of ADP-ribose residues onto target substrates from nicotinamide adenine dinucleotide (NAD) (PARylation) is catalyzed by Poly (ADP-ribose) polymerases (PARPs). Amongst the PARP family members, the DNA damage response in cancer is majorly regulated by PARP1 and PARP2. The blockade of DNA repair by PARP inhibitors leads to the progression of DNA single-strand breaks (induced by some triggering factors) to double-strand breaks. Notably, PARP inhibitors are remarkably effective in cancers with defective homologous recombination repair (HRR). In particular, cancer cells with BRCA mutations are responsive to therapy with PARP inhibitors. The aforementioned requirement for PARP inhibitors to be effective confers a narrow activity spectrum to PARP inhibitors, which hinders their clinical applicability. Thus, the quest to expand the application horizons of PARP inhibitors beyond BRCA mutations is the need of the hour. Literature precedents reveal that HDAC inhibition induces BRCAness in cancer cells and can broaden the therapeutic scope of PARP inhibitors. Driven by such disclosures, dual inhibitors targeting both PARP and HDAC enzymes were designed by our research group to extend the efficacy of PARP inhibitors beyond BRCA-mutated cancers to cancers with induced BRCAness. The design strategy involved the installation of Veliparib, an investigational PARP inhibitor, as a surface recognition part in the HDAC inhibitor pharmacophore model. The chemical architecture of veliparib was deemed appropriate as a starting point for the generation of dual inhibitors by virtue of its size and structural flexibility. A validatory docking study was conducted at the outset to predict the binding mode of the designed dual modulatory chemical architectures. Subsequently, the designed chemical architectures were synthesized via a multistep synthetic route and evaluated for antitumor efficacy. Delightfully, one compound manifested impressive anti-leukemic effects (HL-60 cell lines) mediated via dual inhibition of PARP and class I HDACs. The outcome of the western blot analysis revealed that the compound could downregulate the expression levels of PARP1 and PARP2 and the HDAC isoforms (HDAC1, 2, and 3). Also, the dual PARP-HDAC inhibitor upregulated the protein expression of the acetyl histone H3, confirming its abrogation potential for class I HDACs. In addition, the dual modulator could arrest the cell cycle at the G0/G1 phase and induce autophagy. Further, polymer-based nanoformulation of the dual inhibitor was furnished to afford targeted delivery of the dual inhibitor at the cancer site. Transmission electron microscopy (TEM) results indicate that the nanoparticles were monodispersed and spherical. Moreover, the polymeric nanoformulation exhibited an appropriate particle size. Delightfully, pH-sensitive behavior was manifested by the polymeric nanoformulation that led to selective antitumor effects towards the HL-60 cell lines. In light of the magnificent anti-leukemic profile of the identified dual PARP-HDAC inhibitor, in-vivo studies (pharmacokinetics and pharmacodynamics) are currently being conducted. Notably, the optimistic findings of the aforementioned study have spurred our research group to initiate several medicinal chemistry campaigns to create bifunctional small molecule inhibitors addressing PARP as the primary target.

Keywords: PARP inhibitors, HDAC inhibitors, BRCA mutations, leukemia

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Authors: Parag Katira, Frederika Rentzeperis, Zuzanna Nowicka, Giada Fiandaca, Thomas Veith, Jack Farinhas, Noemi Andor

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Resource limitations shape the outcome of competitions between genetically heterogeneous pre-malignant cells. One example of such heterogeneity is in the ploidy (DNA content) of pre-malignant cells. A whole-genome duplication (WGD) transforms a diploid cell into a tetraploid one and has been detected in 28-56% of human cancers. If a tetraploid subclone expands, it consistently does so early in tumor evolution, when cell density is still low, and competition for nutrients is comparatively weak – an observation confirmed for several tumor types. WGD+ cells need more resources to synthesize increasing amounts of DNA, RNA, and proteins. To quantify resource limitations and how they relate to ploidy, we performed a PAN cancer analysis of WGD, PET/CT, and MRI scans. Segmentation of >20 different organs from >900 PET/CT scans were performed with MOOSE. We observed a strong correlation between organ-wide population-average estimates of Oxygen and the average ploidy of cancers growing in the respective organ (Pearson R = 0.66; P= 0.001). In-vitro experiments using near-diploid and near-tetraploid lineages derived from a breast cancer cell line supported the hypothesis that DNA content influences Glucose- and Oxygen-dependent proliferation-, death- and migration rates. To model how subpopulations with variable DNA content compete in the resource-limited environment of the human brain, we developed a stochastic state-space model of the brain (S3MB). The model discretizes the brain into voxels, whereby the state of each voxel is defined by 8+ variables that are updated over time: stiffness, Oxygen, phosphate, glucose, vasculature, dead cells, migrating cells and proliferating cells of various DNA content, and treat conditions such as radiotherapy and chemotherapy. Well-established Fokker-Planck partial differential equations govern the distribution of resources and cells across voxels. We applied S3MB on sequencing and imaging data obtained from a primary GBM patient. We performed whole genome sequencing (WGS) of four surgical specimens collected during the 1ˢᵗ and 2ⁿᵈ surgeries of the GBM and used HATCHET to quantify its clonal composition and how it changes between the two surgeries. HATCHET identified two aneuploid subpopulations of ploidy 1.98 and 2.29, respectively. The low-ploidy clone was dominant at the time of the first surgery and became even more dominant upon recurrence. MRI images were available before and after each surgery and registered to MNI space. The S3MB domain was initiated from 4mm³ voxels of the MNI space. T1 post and T2 flair scan acquired after the 1ˢᵗ surgery informed tumor cell densities per voxel. Magnetic Resonance Elastography scans and PET/CT scans informed stiffness and Glucose access per voxel. We performed a parameter search to recapitulate the GBM’s tumor cell density and ploidy composition before the 2ⁿᵈ surgery. Results suggest that the high-ploidy subpopulation had a higher Glucose-dependent proliferation rate (0.70 vs. 0.49), but a lower Glucose-dependent death rate (0.47 vs. 1.42). These differences resulted in spatial differences in the distribution of the two subpopulations. Our results contribute to a better understanding of how genomics and microenvironments interact to shape cell fate decisions and could help pave the way to therapeutic strategies that mimic prognostically favorable environments.

Keywords: tumor evolution, intra-tumor heterogeneity, whole-genome doubling, mathematical modeling

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Authors: Andreea Campu, Ilinica Muresan, Simona Cainap, Simion Astilean, Monica Focsan

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Acute myocardial infarction (AMI) is the most severe cardiovascular disease, which has threatened human lives for decades, thus a continuous interest is directed towards the detection of cardiac biomarkers such as cardiac troponin I (cTnI) in order to predict risk and, implicitly, fulfill the early diagnosis requirements in AMI settings. Microfluidics is a major technology involved in the development of efficient sensing devices with real-time fast responses and on-site applicability. Microfluidic devices have gathered a lot of attention recently due to their advantageous features such as high sensitivity and specificity, miniaturization and portability, ease-of-use, low-cost, facile fabrication, and reduced sample manipulation. The integration of gold nanoparticles into the structure of microfluidic sensors has led to the development of highly effective detection systems, considering the unique properties of the metallic nanostructures, specifically the Localized Surface Plasmon Resonance (LSPR), which makes them highly sensitive to their microenvironment. In this scientific context, herein, we propose the implementation of a novel detection device, which successfully combines the efficiency of gold bipyramids (AuBPs) as signal transducers and thermal generators with the sample-driven advantages of the microfluidic channels into a miniaturized, portable, low-cost, specific, and sensitive test for the dual LSPR-thermographic cTnI detection. Specifically, AuBPs with longitudinal LSPR response at 830 nm were chemically synthesized using the seed-mediated growth approach and characterized in terms of optical and morphological properties. Further, the colloidal AuBPs were deposited onto pre-treated silanized glass substrates thus, a uniform nanoparticle coverage of the substrate was obtained and confirmed by extinction measurements showing a 43 nm blue-shift of the LSPR response as a consequence of the refractive index change. The as-obtained plasmonic substrate was then integrated into a microfluidic “Y”-shaped polydimethylsiloxane (PDMS) channel, fabricated using a Laser Cutter system. Both plasmonic and microfluidic elements were plasma treated in order to achieve a permanent bond. The as-developed microfluidic plasmonic chip was further coupled to an automated syringe pump system. The proposed biosensing protocol implicates the successive injection inside the microfluidic channel as follows: p-aminothiophenol and glutaraldehyde, to achieve a covalent bond between the metallic surface and cTnI antibody, anti-cTnI, as a recognition element, and target cTnI biomarker. The successful functionalization and capture of cTnI was monitored by LSPR detection thus, after each step, a red-shift of the optical response was recorded. Furthermore, as an innovative detection technique, thermal determinations were made after each injection by exposing the microfluidic plasmonic chip to 785 nm laser excitation, considering that the AuBPs exhibit high light-to-heat conversion performances. By the analysis of the thermographic images, thermal curves were obtained, showing a decrease in the thermal efficiency after the anti-cTnI-cTnI reaction was realized. Thus, we developed a microfluidic plasmonic chip able to operate as both LSPR and thermal sensor for the detection of the cardiac troponin I biomarker, leading thus to the progress of diagnostic devices.

Keywords: gold nanobipyramids, microfluidic device, localized surface plasmon resonance detection, thermographic detection

Procedia PDF Downloads 128

Authors: Tahani Mashikhi

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Countries worldwide rely on electric power as a critical economic growth and progress factor. Renewable energy sources, often referred to as alternative energy sources, such as wind, solar energy, geothermal energy, biomass, and hydropower, have garnered significant interest in response to the rising consumption of fossil fuels. Dye-sensitized solar cells (DSSCs) are a highly promising alternative for energy production as they possess numerous advantages compared to traditional silicon solar cells and thin-film solar cells. These include their low cost, high flexibility, straightforward preparation methodology, ease of production, low toxicity, different colors, semi-transparent quality, and high power conversion efficiency. A solar cell, also known as a photovoltaic cell, is a device that converts the energy of light from the sun into electrical energy through the photovoltaic effect. The Gratzel cell is the initial dye-sensitized solar cell made from colloidal titanium dioxide. The operational mechanism of DSSCs relies on various key elements, such as a layer composed of wide band gap semiconducting oxide materials (e.g. titanium dioxide [TiO₂]), as well as a photosensitizer or dye that absorbs sunlight to inject electrons into the conduction band, the electrolyte utilizes the triiodide/iodide redox pair (I− /I₃−) to regenerate dye molecules and a counter electrode made of carbon or platinum facilitates the movement of electrons across the circuit. Electrospray deposition permits the deposition of fragile, non-volatile molecules in a vacuum environment, including dye sensitizers, complex molecules, nanoparticles, and biomolecules. Surface science techniques, particularly X-ray photoelectron spectroscopy, are employed to examine dye-sensitized solar cells. This study investigates the possible application of electrospray deposition to build high-quality layers in situ in a vacuum. Two distinct categories of dyes can be employed as sensitizers in DSSCs: organometallic semiconductor sensitizers and purely organic dyes. Most organometallic dyes, including Ru533, RuC, and RuP, contain a ruthenium atom, which is a rare element. This ruthenium atom enhances the efficiency of dye-sensitized solar cells (DSSCs). These dyes are characterized by their high cost and typically appear as dark purple powders. On the other hand, organic dyes, such as SQ2, RK1, D5, SC4, and R6, exhibit reduced efficacy due to the lack of a ruthenium atom. These dyes appear in green, red, orange, and blue powder-colored. This study will specifically concentrate on metal-organic dyes. The adsorption of dye molecules onto the rutile TiO₂ (110) surface has been deposited in situ under ultra-high vacuum conditions by combining an electrospray deposition method with X-ray photoelectron spectroscopy. The X-ray photoelectron spectroscopy (XPS) technique examines chemical bonds and interactions between molecules and TiO₂ surfaces. The dyes were deposited at varying times, from 5 minutes to 40 minutes, to achieve distinct layers of coverage categorized as sub-monolayer, monolayer, few layers, or multilayer. Based on the O 1s photoelectron spectra data, it can be observed that the monolayer establishes a strong chemical bond with the Ti atoms of the oxide substrate by deprotonating the carboxylic acid groups through 2M-bidentate bridging anchors. The C 1s and N 1s photoelectron spectra indicate that the molecule remains intact at the surface. This can be due to the existence of all functional groups and a ruthenium atom, where the binding energy of Ru 3d is consistent with Ru2+.

Keywords: deposit, dye, electrospray, TiO₂, XPS

Procedia PDF Downloads 43

Authors: Merrick Lopez, Aashish Abraham, Melissa Egge, Marissa Hood, Jui Shah

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A 3 year old male with unknown medical history presented initially with encephalopathy, intubated for respiratory failure, and admitted to the pediatric intensive care unit (PICU) with refractory shock. During resuscitation in the emergency department, he was found to be in severe metabolic acidosis with a pH of 7.03 and escalated on vasopressor drips for hypotension. His initial sodium was 174. He was noted to have burn injuries to his scalp, forehead, right axilla, bilateral arm creases and lower legs. He had rhabdomyolysis (initial creatinine kinase 5,430 U/L with peak levels of 62,340 normal <335 U/L), cardiac injury (initial troponin 88 ng/L with peak at 145 ng/L, normal <15ng/L), hypernatremia (peak 174, normal 140), hypocalcemia, liver injury, acute kidney injury, and neuronal loss on magnetic resonance imaging (MRI). Soft restraints and a shock collar were found in the home. He was critically ill for 8 days, but was gradually weaned off drips, extubated, and started on feeds. Discussion Electrical injury, specifically lightning injury is an uncommon but devastating cause of injury in pediatric patients. This patient with suspected abusive use of a dog shock collar presented similar to a lightning strike. Common entrance points include the hands and head, similar to our patient with linear wounds on his forehead. When current enters, it passes through tissues with the least resistance. Nerves, blood vessels, and muscles, have high fluid and electrolyte content and are commonly affected. Exit points are extremities: our child who had circumferential burns around his arm creases and ankles. Linear burns preferentially follow areas of high sweat concentration, and are thought to be due to vaporization of water on the skin’s surface. The most common cause of death from a lightning strike is due to cardiopulmonary arrest. The massive depolarization of the myocardium can result in arrhythmias and myocardial necrosis. The patient presented in cardiogenic shock with evident cardiac damage. Electricity going through vessels can lead to vaporization of intravascular water. This can explain his severe hypernatremia. He also sustained other internal organ injuries (adrenal glands, pancreas, liver, and kidney). Electrical discharge also leads to direct skeletal muscle injury in addition to prolonged muscular spasm. Rhabdomyolysis, the acute damage of muscle, leads to release of potentially toxic components into the circulation which could lead to acute renal failure. The patient had severe rhabdomyolysis and renal injury. Early hypocalcemia has been consistently demonstrated in patients with rhabdomyolysis. This was present in the patient and led to increased vasopressor needs. Central nervous system injuries are also common which can include encephalopathy, hypoxic injury, and cerebral infarction. The patient had evidence of brain injury as seen on MRI. Conclusion Electrical injuries due to lightning strikes and abusive use of a dog shock collar are rare, but can both present in similar ways with respiratory failure, shock, hypernatremia, rhabdomyolysis, brain injury, and multiorgan damage. Although rare, it is essential for early identification and prompt management for acute and chronic complications in these children.

Keywords: cardiogenic shock, dog shock collar, lightning strike, rhabdomyolysis

Procedia PDF Downloads 86

Authors: Wellemans Isabelle, Remmelink Myriam, Foucart Annick, Rusu Stefan, Compère Christophe

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Primary pulmonary meningioma (PPM) is a very rare tumor, and its occurrence has been reported only sporadically. Multiple PPMs are even more exceptional, and herein, we report, to the best of our knowledge, the fourth case, focusing on the clinicopathological features of the tumor. Moreover, the possible relationship between the use of progesterone–only contraceptives and the development of these neoplasms will be discussed. Case Report: We report a case of a 51-year-old female presenting three solid pulmonary nodules, with the following localizations: right upper lobe, middle lobe, and left lower lobe, described as incidental findings on computed tomography (CT) during a pre-bariatric surgery check-up. The patient revealed no drinking or smoking history. The physical exam was unremarkable except for the obesity. The lesions ranged in size between 6 and 24 mm and presented as solid nodules with lobulated contours. The largest lesion situated in the middle lobe had mild fluorodeoxyglucose (FDG) uptake on F-18 FDG positron emission tomography (PET)/CT, highly suggestive of primary lung neoplasm. For pathological assessment, video-assisted thoracoscopic middle lobectomy and wedge resection of the right upper nodule was performed. Histological examination revealed relatively well-circumscribed solid proliferation of bland meningothelial cells growing in whorls and lobular nests, presenting intranuclear pseudo-inclusions and psammoma bodies. No signs of anaplasia were observed. The meningothelial cells expressed diffusely Vimentin, focally Progesterone receptors and were negative for epithelial (cytokeratin (CK) AE1/AE3, CK7, CK20, Epithelial Membrane Antigen (EMA)), neuroendocrine markers (Synaptophysin, Chromogranin, CD56) and Estrogenic receptors. The proliferation labelling index Ki-67 was low (<5%). Metastatic meningioma was ruled out by brain and spine magnetic resonance imaging (MRI) scans. The third lesion localized in the left lower lobe was followed-up and resected three years later because of its slow but significant growth (14 mm to 16 mm), alongside two new infra centimetric lesions. Those three lesions showed a morphological and immunohistochemical profile similar to previously resected lesions. The patient was disease-free one year post-last surgery. Discussion: Although PPMs are mostly benign and slow-growing tumors with an excellent prognosis, they do not present specific radiological characteristics, and it is difficult to differentiate it from other lung tumors, histopathologic examination being essential. Aggressive behavior is associated with atypical or anaplastic features (WHO grades II–III) The etiology is still uncertain and different mechanisms have been proposed. A causal connection between sexual hormones and meningothelial proliferation has long been suspected and few studies examining progesterone only contraception and meningioma risk have all suggested an association. In line with this, our patient was treated with Levonorgestrel, a progesterone agonist, intra-uterine device (IUD). Conclusions: PPM, defined by the typical histological and immunohistochemical features of meningioma in the lungs and the absence of central nervous system lesions, is an extremely rare neoplasm, mainly solitary and associating, and indolent growth. Because of the unspecific radiologic findings, it should always be considered in the differential diagnosis of lung neoplasms. Regarding multiple PPM, only three cases are reported in the literature, and this is the first described in a woman treated by a progesterone-only IUD to the best of our knowledge.

Keywords: pulmonary meningioma, multiple meningioma, meningioma, pulmonary nodules

Procedia PDF Downloads 112

Authors: Patrizia Firmani, Sara Perucchini, Irene Rapone, Raffella Borrelli, Stefano Chiaberge, Manuela Grande, Rosamaria Marrazzo, Alberto Savoini, Andrea Siviero, Silvia Spera, Fabio Vago, Davide Deriu, Sergio Fanutti, Alessandro Oldani

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According to the Renewable Energy Directive II, the use of palm oil in diesel will be gradually reduced from 2023 and should reach zero in 2030 due to the deforestation caused by its production. Eni aims at finding alternative feedstocks for its biorefineries to eliminate the use of palm oil by 2023. Therefore, the ideal vegetable oils to be used in bio-refineries are those obtainable from plants that grow in marginal lands and with low impact on food-and-feed chain; hence, Eni research is studying the possibility of using oleaginous seeds, such as castor, croton, and cotton, to extract the oils to be exploited as feedstock in bio-refineries. To verify their suitability for the upgrading processes, an analytical protocol for their characterization has been drawn up and applied. The analytical characterizations include a step of water and ashes content determination, elemental analysis (CHNS analysis, X-Ray Fluorescence, Inductively Coupled Plasma - Optical Emission Spectroscopy, ICP– Mass Spectrometry), and total acid number determination. Gas chromatography coupled to flame ionization detector (GC-FID) is used to quantify the lipid content in terms of free fatty acids, mono-, di- and triacylglycerols, and fatty acids composition. Eventually, Nuclear Magnetic Resonance and Fourier Transform-Infrared spectroscopies are exploited with GC-MS and Fourier Transform-Ion Cyclotron Resonance to study the composition of the oils. This work focuses on the GC-FID analysis of the lipid fraction of these oils, as the main constituent and of greatest interest for bio-refinery processes. Specifically, the lipid component of the extracted oil was quantified after sample silanization and transmethylation: silanization allows the elution of high-boiling compounds and is useful for determining the quantity of free acids and glycerides in oils, while transmethylation leads to a mixture of fatty acid esters and glycerol, thus allowing to evaluate the composition of glycerides in terms of Fatty Acids Methyl Esters (FAME). Cotton oil was extracted from cotton oilcake, croton oil was obtained by seeds pressing and seeds and oilcake ASE extraction, while castor oil comes from seed pressing (not performed in Eni laboratories). GC-FID analyses reported that the cotton oil is 90% constituted of triglycerides and about 6% diglycerides, while free fatty acids are about 2%. In terms of FAME, C18 acids make up 70% of the total and linoleic acid is the major constituent. Palmitic acid is present at 17.5%, while the other acids are in low concentration (<1%). Both analyzes show the presence of non-gas chromatographable compounds. Croton oils from seed pressing and extraction mainly contain triglycerides (98%). Concerning FAME, the main component is linoleic acid (approx. 80%). Oilcake croton oil shows higher abundance of diglycerides (6% vs ca 2%) and a lower content of triglycerides (38% vs 98%) compared to the previous oils. Eventually, castor oil is mostly constituted of triacylglycerols (about 69%), followed by diglycerides (about 10%). About 85.2% of total FAME is ricinoleic acid, as a constituent of triricinolein, the most abundant triglyceride of castor oil. Based on the analytical results, these oils represent feedstocks of interest for possible exploitation as advanced biofuels.

Keywords: analytical protocol, biofuels, biorefinery, gas chromatography, vegetable oil

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Authors: Sajeli A. Begum, Ameer Basha, Kirti Hira, Rukaiyya Khan

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Cyclic dipeptides are simple diketopiperazine derivatives being investigated by several scientists for their biological effects which include anticancer, antimicrobial, haematological, anticonvulsant, immunomodulatory effect, etc. They are potentially active microbial metabolites having been synthesized too, for developing into drug candidates. Cultures of Pseudomonas species have earlier been reported to produce cyclic dipeptides, helping in quorum sensing signals and bacterial–host colonization phenomena during infections, causing cell anti-proliferation and immunosuppression. Fluorescing Pseudomonas species have been identified to secrete lipid derivatives, peptides, pyrroles, phenazines, indoles, aminoacids, pterines, pseudomonic acids and some antibiotics. In the present work, results of investigation on the cyclic dipeptide metabolites secreted by the culture broth of Pseudomonas species as potent pro-inflammatory cytokine inhibitors are discussed. The bacterial strain was isolated from the rhizospheric soil of groundnut crop and identified as Pseudomonas aeruginosa by 16S rDNA sequence (GenBank Accession No. KT625586). Culture broth of this strain was prepared by inoculating into King’s B broth and incubating at 30 ºC for 7 days. The ethyl acetate extract of culture broth was prepared and lyophilized to get a dry residue (EEPA). Lipopolysaccharide (LPS)-induced ELISA assay proved the inhibition of tumor necrosis factor-alpha (TNF-α) secretion in culture supernatant of RAW 264.7 cells by EEPA (IC50 38.8 μg/mL). The effect of oral administration of EEPA on plasma TNF-α level in rats was tested by ELISA kit. The LPS mediated plasma TNF-α level was reduced to 45% with 125 mg/kg dose of EEPA. Isolation of the chemical constituents of EEPA through column chromatography yielded ten cyclic dipeptides, which were characterized using nuclear magnetic resonance and mass spectroscopic techniques. These cyclic dipeptides are biosynthesized in microorganisms by multifunctional assembly of non-ribosomal peptide synthases and cyclic dipeptide synthase. Cyclo (Gly-L-Pro) was found to be more potentially (IC50 value 4.5 μg/mL) inhibiting TNF-α production followed by cyclo (trans-4-hydroxy-L-Pro-L-Phe) (IC50 value 14.2 μg/mL) and the effect was equal to that of standard immunosuppressant drug, prednisolone. Further, the effect was analyzed by determining mRNA expression of TNF-α in LPS-stimulated RAW 264.7 macrophages using quantitative real-time reverse transcription polymerase chain reaction. EEPA and isolated cyclic dipeptides demonstrated diminution of TNF-α mRNA expression levels in a dose-dependent manner under the tested conditions. Also, they were found to control the expression of other pro-inflammatory cytokines like IL-1β and IL-6, when tested through their mRNA expression levels in LPS-stimulated RAW 264.7 macrophages under LPS-stimulated conditions. In addition, significant inhibition effect was found on Nitric oxide production. Further all the compounds exhibited weak toxicity to LPS-induced RAW 264.7 cells. Thus the outcome of the study disclosed the effectiveness of EEPA and the isolated cyclic dipeptides in down-regulating key cytokines involved in pathophysiology of autoimmune diseases.In another study led by the investigators, microbial cyclic dipeptides were found to exhibit excellent antimicrobial effect against Fusarium moniliforme which is an important causative agent of Sorghum grain mold disease. Thus, cyclic dipeptides are emerging small molecular drug candidates for various autoimmune diseases.

Keywords: cyclic dipeptides, cytokines, Fusarium moniliforme, Pseudomonas, TNF-alpha

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Authors: Yasar Samet Gokceoglu, Ayse Nur Incesu, Furkan Okatar, Berk Nimetoglu, Serkan Bayram, Turgut Akgul

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Ankle syndesmosis injuries pose a significant challenge in orthopedic practice due to their potential for prolonged recovery and chronic ankle dysfunction. Accurate diagnosis and management of these injuries are essential for achieving optimal patient outcomes. The use of radiological methods, such as X-ray, computed tomography (CT), and magnetic resonance imaging (MRI), plays a vital role in the accurate diagnosis of syndesmosis injuries in the context of ankle fractures. Treatment options for ankle syndesmosis injuries vary, with surgical interventions such as screw fixation and suture-button implantation being commonly employed. The choice of treatment is influenced by the severity of the injury and the presence of associated fractures. Additionally, the mechanism of injury, such as pure syndesmosis injury or specific fracture types, can impact the stability and management of syndesmosis injuries. Ankle fractures with syndesmosis injury present a complex clinical scenario, requiring accurate diagnosis, appropriate reduction, and tailored management strategies. The interplay between the mechanism of injury, associated fractures, and treatment modalities significantly influences the outcomes of these challenging injuries. The long-term outcomes and patient satisfaction following ankle fractures with syndesmosis injury are crucial considerations in the field of orthopedics. Patient-reported outcome measures, such as the Foot and Ankle Outcome Score (FAOS), provide essential information about functional recovery and quality of life after these injuries. When diagnosing syndesmosis injuries, standard measurements, such as the medial clear space, tibiofibular overlap, tibiofibular clear space, anterior tibiofibular ratio (ATFR), and the anterior-posterior tibiofibular ratio (APTF), are assessed through radiographs and computed tomography (CT) scans. These parameters are critical in evaluating the presence and severity of syndesmosis injuries, enabling clinicians to choose the most appropriate treatment approach. Despite advancements in diagnostic imaging, challenges remain in accurately diagnosing and treating ankle syndesmosis injuries. Traditional diagnostic parameters, while beneficial, may not capture the full extent of the injury or provide sufficient information to guide therapeutic decisions. This gap highlights the need for exploring additional diagnostic parameters that could enhance the accuracy of syndesmosis injury diagnoses and inform treatment strategies more effectively. The primary goal of this research is to evaluate the usefulness of traditional radiographic measurements in comparison to new CT-based measurements for diagnosing ankle syndesmosis injuries. Specifically, this study aims to assess the accuracy of conventional parameters, including medial clear space, tibiofibular overlap, tibiofibular clear space, ATFR, and APTF, in contrast with the recently proposed CT-based measurements such as the delta and gamma angles. Moreover, the study intends to explore the relationship between these diagnostic parameters and functional outcomes, as measured by the Foot and Ankle Outcome Score (FAOS). Establishing a correlation between specific diagnostic measurements and FAOS scores will enable us to identify the most reliable predictors of functional recovery following syndesmosis injuries. This comparative analysis will provide valuable insights into the accuracy and dependability of CT-based measurements in diagnosing ankle syndesmosis injuries and their potential impact on predicting patient outcomes. The results of this study could greatly influence clinical practices by refining diagnostic criteria and optimizing treatment planning for patients with ankle syndesmosis injuries.

Keywords: ankle syndesmosis injury, diagnostic accuracy, computed tomography, radiographic measurements, Tibiofibular syndesmosis distance

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Authors: Nino Kupatadze, Tamar Memanishvili, Natia Ochkhikidze, David Tugushi, Zaal Kokaia, Ramaz Katsarava

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Amino acid-based Biodegradable poly(ester-amide)s (PEAs) have gained considerable interest as a promising materials for numerous biomedical applications. These polymers reveal a high biocompatibility and easily form small particles suitable for delivery various biological, as well as elastic bio-erodible films serving as matrices for constructing antibacterial coatings. In the present work we have demonstrated a potential of the PEAs for two applications: 1. cell therapy for stroke as vehicles for delivery and sustained release of growth factors, 2. bactericidal coating as prevention biofilm and applicable in infected wound management. Stroke remains the main cause of adult disability with limited treatment options. Although stem cell therapy is a promising strategy, it still requires improvement of cell survival, differentiation and tissue modulation. .Recently, microspheres (MPs) made of biodegradable polymers have gained significant attention for providing necessary support of transplanted cells. To investigate this strategy in the cell therapy of stroke, MPs loaded with transcription factors Wnt3A/BMP4 were prepared. These proteins have been shown to mediate the maturation of the cortical neurons. We have suggested that implantation of these materials could create a suitable microenvironment for implanted cells. Particles with spherical shape, porous surface, and 5-40 m in size (monitored by scanning electron microscopy) were made on the basis of the original PEA composed of adipic acid, L-phenylalanine and 1,4-butanediol. After 4 months transplantation of MPs in rodent brain, no inflammation was observed. Additionally, factors were successfully released from MPs and affected neuronal cell differentiation in in vitro. The in vivo study using loaded MPs is in progress. Another severe problem in biomedicine is prevention of surgical devices from biofilm formation. Antimicrobial polymeric coatings are most effective “shields” to protect surfaces/devices from biofilm formation. Among matrices for constructing the coatings preference should be given to bio-erodible polymers. Such types of coatings will play a role of “unstable seating” that will not allow bacteria to occupy the surface. In other words, bio-erodible coatings would be discomfort shelter for bacteria that along with releasing “killers of bacteria” should prevent the formation of biofilm. For this purpose, we selected an original biodegradable PEA composed of L-leucine, 1,6-hexanediol and sebacic acid as a bio-erodible matrix, and nanosilver (AgNPs) as a bactericidal agent (“killer of bacteria”). Such nanocomposite material is also promising in treatment of superficial wound and ulcer. The solubility of the PEA in ethanol allows to reduce AgNO3 to NPs directly in the solution, where the solvent served as a reductive agent, and the PEA served as NPs stabilizer. The photochemical reduction was selected as a basic method to form NPs. The obtained AgNPs were characterized by UV-spectroscopy, transmission electron microscope (TEM), and dynamic light scattering (DLS). According to the UV-data and TEM data the photochemical reduction resulted in spherical AgNPs with wide particle size distribution with a high contribution of the particles below 10 nm that are known as responsible for bactericidal activity of AgNPs. DLS study showed that average size of nanoparticles formed after photo-reduction in ethanol solution ranged within ca. 50 nm.

Keywords: biodegradable polymers, microparticles, nanocomposites, stem cell therapy, stroke

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Authors: Katerina Zaharieva, Katya Milenova, Zara Cherkezova-Zheleva, Alexander Eliyas, Boris Kunev, Ivan Mitov

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The synthesized nanosized manganese ferrite-type of samples have been tested as photocatalysts in the reaction of oxidative degradation of model contaminant Reactive Black 5 (RB5) dye in aqueous solutions under UV irradiation. As it is known this azo dye is applied in the textile-coloring industry and it is discharged into the waterways causing pollution. The co-precipitation procedure has been used for the synthesis of manganese ferrite-type of materials: Sample 1 - Mn0.25Fe2.75O4, Sample 2 - Mn0.5Fe2.5O4 and Sample 3 - MnFe2O4 from 0.03M aqueous solutions of MnCl2•4H2O, FeCl2•4H2O and/or FeCl3•6H2O and 0.3M NaOH in appropriate amounts. The mechanochemical activation of co-precipitated ferrite-type of samples has been performed in argon (Samples 1 and 2) or in air atmosphere (Sample 3) for 2 hours at a milling speed of 500 rpm. The mechano-chemical treatment has been carried out in a high energy planetary ball mill type PM 100, Retsch, Germany. The mass ratio between balls and powder was 30:1. As a result mechanochemically activated Sample 4 - Mn0.25Fe2.75O4, Sample 5 - Mn0.5Fe2.5O4 and Sample 6 - MnFe2O4 have been obtained. The synthesized manganese ferrite-type photocatalysts have been characterized by X-ray diffraction method and Moessbauer spectroscopy. The registered X-ray diffraction patterns and Moessbauer spectra of co-precipitated ferrite-type of materials show the presence of manganese ferrite and additional akaganeite phase. The presence of manganese ferrite and small amounts of iron phases is established in the mechanochemically treated samples. The calculated average crystallite size of manganese ferrites varies within the range 7 – 13 nm. This result is confirmed by Moessbauer study. The registered spectra show superparamagnetic behavior of the prepared materials at room temperature. The photocatalytic investigations have been made using polychromatic UV-A light lamp (Sylvania BLB, 18 W) illumination with wavelength maximum at 365 nm. The intensity of light irradiation upon the manganese ferrite-type photocatalysts was 0.66 mW.cm-2. The photocatalytic reaction of oxidative degradation of RB5 dye was carried out in a semi-batch slurry photocatalytic reactor with 0.15 g of ferrite-type powder, 150 ml of 20 ppm dye aqueous solution under magnetic stirring at rate 400 rpm and continuously feeding air flow. The samples achieved adsorption-desorption equilibrium in the dark period for 30 min and then the UV-light was turned on. After regular time intervals aliquot parts from the suspension were taken out and centrifuged to separate the powder from solution. The residual concentrations of dye were established by a UV-Vis absorbance single beam spectrophotometer CamSpec M501 (UK) measuring in the wavelength region from 190 to 800 nm. The photocatalytic measurements determined that the apparent pseudo-first-order rate constants calculated by linear slopes approximating to first order kinetic equation, increase in following order: Sample 3 (1.1х10-3 min-1) < Sample 1 (2.2х10-3 min-1) < Sample 2 (3.3 х10-3 min-1) < Sample 4 (3.8х10-3 min-1) < Sample 6 (11х10-3 min-1) < Sample 5 (15.2х10-3 min-1). The mechanochemically activated manganese ferrite-type of photocatalyst samples show significantly higher degree of oxidative degradation of RB5 dye after 120 minutes of UV light illumination in comparison with co-precipitated ferrite-type samples: Sample 5 (92%) > Sample 6 (91%) > Sample 4 (63%) > Sample 2 (53%) > Sample 1 (42%) > Sample 3 (15%). Summarizing the obtained results we conclude that the mechanochemical activation leads to a significant enhancement of the degree of oxidative degradation of the RB5 dye and photocatalytic activity of tested manganese ferrite-type of catalyst samples under our experimental conditions. The mechanochemically activated Mn0.5Fe2.5O4 ferrite-type of material displays the highest photocatalytic activity (15.2х10-3 min-1) and degree of oxidative degradation of the RB5 dye (92%) compared to the other synthesized samples. Especially a significant improvement in the degree of oxidative degradation of RB5 dye (91%) has been determined for mechanochemically treated MnFe2O4 ferrite-type of sample with the highest extent of substitution of iron ions by manganese ions than in the case of the co-precipitated MnFe2O4 sample (15%). The mechanochemically activated manganese ferrite-type of samples show good photocatalytic properties in the reaction of oxidative degradation of RB5 azo dye in aqueous solutions and it could find potential application for dye removal from wastewaters originating from textile industry.

Keywords: nanostructured manganese ferrite-type materials, photocatalytic activity, Reactive Black 5, water treatment

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Authors: Claire Harrison, Raajit K. Rampal, Vikas Gupta, Srdan Verstovsek, Moshe Talpaz, Jean-Jacques Kiladjian, Ruben Mesa, Andrew Kuykendall, Alessandro Vannucchi, Francesca Palandri, Sebastian Grosicki, Timothy Devos, Eric Jourdan, Marielle J. Wondergem, Haifa Kathrin Al-Ali, Veronika Buxhofer-Ausch, Alberto Alvarez-Larrán, Sanjay Akhani, Rafael Muñoz-Carerras, Yury Sheykin, Gozde Colak, Morgan Harris, John Mascarenhas

Abstract:

Myelofibrosis (MF) is characterized by bone marrow fibrosis, anemia, splenomegaly and constitutional symptoms. Progressive bone marrow fibrosis results from aberrant megakaryopoeisis and expression of proinflammatory cytokines, both of which are heavily influenced by bromodomain and extraterminal domain (BET)-mediated gene regulation and lead to myeloproliferation and cytopenias. Pelabresib (CPI-0610) is an oral small-molecule investigational inhibitor of BET protein bromodomains currently being developed for the treatment of patients with MF. It is designed to downregulate BET target genes and modify nuclear factor kappa B (NF-κB) signaling. MANIFEST-2 was initiated based on data from Arm 3 of the ongoing Phase 2 MANIFEST study (NCT02158858), which is evaluating the combination of pelabresib and ruxolitinib in Janus kinase inhibitor (JAKi) treatment-naïve patients with MF. Primary endpoint analyses showed splenic and symptom responses in 68% and 56% of 84 enrolled patients, respectively. MANIFEST-2 (NCT04603495) is a global, Phase 3, randomized, double-blind, active-control study of pelabresib and ruxolitinib versus placebo and ruxolitinib in JAKi treatment-naïve patients with primary MF, post-polycythemia vera MF or post-essential thrombocythemia MF. The aim of this study is to evaluate the efficacy and safety of pelabresib in combination with ruxolitinib. Here we report updates from a recent protocol amendment. The MANIFEST-2 study schema is shown in Figure 1. Key eligibility criteria include a Dynamic International Prognostic Scoring System (DIPSS) score of Intermediate-1 or higher, platelet count ≥100 × 10^9/L, spleen volume ≥450 cc by computerized tomography or magnetic resonance imaging, ≥2 symptoms with an average score ≥3 or a Total Symptom Score (TSS) of ≥10 using the Myelofibrosis Symptom Assessment Form v4.0, peripheral blast count <5% and Eastern Cooperative Oncology Group performance status ≤2. Patient randomization will be stratified by DIPSS risk category (Intermediate-1 vs Intermediate-2 vs High), platelet count (>200 × 10^9/L vs 100–200 × 10^9/L) and spleen volume (≥1800 cm^3 vs <1800 cm^3). Double-blind treatment (pelabresib or matching placebo) will be administered once daily for 14 consecutive days, followed by a 7 day break, which is considered one cycle of treatment. Ruxolitinib will be administered twice daily for all 21 days of the cycle. The primary endpoint is SVR35 response (≥35% reduction in spleen volume from baseline) at Week 24, and the key secondary endpoint is TSS50 response (≥50% reduction in TSS from baseline) at Week 24. Other secondary endpoints include safety, pharmacokinetics, changes in bone marrow fibrosis, duration of SVR35 response, duration of TSS50 response, progression-free survival, overall survival, conversion from transfusion dependence to independence and rate of red blood cell transfusion for the first 24 weeks. Study recruitment is ongoing; 400 patients (200 per arm) from North America, Europe, Asia and Australia will be enrolled. The study opened for enrollment in November 2020. MANIFEST-2 was initiated based on data from the ongoing Phase 2 MANIFEST study with the aim of assessing the efficacy and safety of pelabresib and ruxolitinib in JAKi treatment-naïve patients with MF. MANIFEST-2 is currently open for enrollment.

Keywords: CPI-0610, JAKi treatment-naïve, MANIFEST-2, myelofibrosis, pelabresib

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Authors: Ali Kadir, S. R. Mishra, M. Shamshuddin, O. Anwar Beg

Abstract:

Motivation- Rotating disk bio-reactors are fundamental to numerous medical/biochemical engineering processes including oxygen transfer, chromatography, purification and swirl-assisted pumping. The modern upsurge in biologically-enhanced engineering devices has embraced new phenomena including bioconvection of micro-organisms (photo-tactic, oxy-tactic, gyrotactic etc). The proven thermal performance superiority of nanofluids i.e. base fluids doped with engineered nanoparticles has also stimulated immense implementation in biomedical designs. Motivated by these emerging applications, we present a numerical thermofluid dynamic simulation of the transport phenomena in bioconvection nanofluid rotating disk bioreactor flow. Methodology- We study analytically and computationally the time-dependent three-dimensional viscous gyrotactic bioconvection in swirling nanofluid flow from a rotating disk configuration. The disk is also deformable i.e. able to extend (stretch) in the radial direction. Stefan blowing is included. The Buongiorno dilute nanofluid model is adopted wherein Brownian motion and thermophoresis are the dominant nanoscale effects. The primitive conservation equations for mass, radial, tangential and axial momentum, heat (energy), nanoparticle concentration and micro-organism density function are formulated in a cylindrical polar coordinate system with appropriate wall and free stream boundary conditions. A mass convective condition is also incorporated at the disk surface. Forced convection is considered i.e. buoyancy forces are neglected. This highly nonlinear, strongly coupled system of unsteady partial differential equations is normalized with the classical Von Karman and other transformations to render the boundary value problem (BVP) into an ordinary differential system which is solved with the efficient Adomian decomposition method (ADM). Validation with earlier Runge-Kutta shooting computations in the literature is also conducted. Extensive computations are presented (with the aid of MATLAB symbolic software) for radial and circumferential velocity components, temperature, nanoparticle concentration, micro-organism density number and gradients of these functions at the disk surface (radial local skin friction, local circumferential skin friction, Local Nusselt number, Local Sherwood number, motile microorganism mass transfer rate). Main Findings- Increasing radial stretching parameter decreases radial velocity and radial skin friction, reduces azimuthal velocity and skin friction, decreases local Nusselt number and motile micro-organism mass wall flux whereas it increases nano-particle local Sherwood number. Disk deceleration accelerates the radial flow, damps the azimuthal flow, decreases temperatures and thermal boundary layer thickness, depletes the nano-particle concentration magnitudes (and associated nano-particle species boundary layer thickness) and furthermore decreases the micro-organism density number and gyrotactic micro-organism species boundary layer thickness. Increasing Stefan blowing accelerates the radial flow and azimuthal (circumferential flow), elevates temperatures of the nanofluid, boosts nano-particle concentration (volume fraction) and gyrotactic micro-organism density number magnitudes whereas suction generates the reverse effects. Increasing suction effect reduces radial skin friction and azimuthal skin friction, local Nusselt number, and motile micro-organism wall mass flux whereas it enhances the nano-particle species local Sherwood number. Conclusions - Important transport characteristics are identified of relevance to real bioreactor nanotechnological systems not discussed in previous works. ADM is shown to achieve very rapid convergence and highly accurate solutions and shows excellent promise in simulating swirling multi-physical nano-bioconvection fluid dynamics problems. Furthermore, it provides an excellent complement to more general commercial computational fluid dynamics simulations.

Keywords: bio-nanofluids, rotating disk bioreactors, Von Karman swirling flow, numerical solutions

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