Search results for: irradiation fluence

Authors: Sajmina Khatun, Monika Pebam, Aravind Kumar Rengan

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Photothermal therapy, a subset of nanomedicine, takes advantage of light-absorbing agents to generate localized heat, selectively eradicating cancer cells. This innovative approach minimizes damage to healthy tissues and offers a promising avenue for targeted cancer treatment. Unlike conventional therapies, photothermal therapy harnesses the power of light to combat malignancies precisely and effectively, showcasing its potential to revolutionize cancer treatment paradigms. The combined strengths of nanomedicine and photothermal therapy signify a transformative shift toward more effective, targeted, and tolerable cancer treatments in the medical landscape. Utilizing natural products becomes instrumental in formulating diverse bioactive medications owing to their various pharmacological properties attributed to the existence of phenolic structures, triterpenoids, and similar compounds. Hyptis suaveolens, commonly known as pignut, stands as an aromatic herb within the Lamiaceae family and represents a valuable therapeutic plant. Flourishing in swamps and alongside tropical and subtropical roadsides, these noxious weeds impede the development of adjacent plants. Hyptis suaveolens ranks among the most globally distributed alien invasive species. The present investigation revealed that a versatile, biodegradable liposome nanosystem (HIL NPs), incorporating bioactive molecules from Hyptis suaveolens, exhibits effective bioavailability to cancer cells, enabling tumor ablation upon near-infrared (NIR) laser exposure. The components within the nanosystem, specifically the bioactive molecules from Hyptis, function as anticancer agents, aiding in the photothermal ablation of highly metastatic lung cancer cells. Despite being a prolific weed impeding neighboring plant growth, Hyptis suaveolens showcases therapeutic benefits through its bioactive compounds. The obtained HIL NPs, characterized as a photothermally active liposome nanosystem, demonstrate a pronounced fluorescence absorption peak in the NIR range and achieve a high photothermal conversion efficiency under NIR laser irradiation. Transmission electron microscopy (TEM) and particle size analysis reveal that HIL NPs possess a spherical shape with a size of 141 ± 30 nm. Moreover, in vitro assessments of HIL NPs against lung cancer cell lines (A549) indicate effective anticancer activity through a combined cytotoxic effect and hyperthermia. Tumor ablation is facilitated by apoptosis induced by the overexpression of ɣ-H2AX, arresting cancer cell proliferation. Consequently, the multifunctional and biodegradable nanosystem (HIL NPs), incorporating bioactive compounds from Hyptis, provides valuable perspectives for developing an innovative therapeutic strategy originating from a challenging weed. This approach holds promise for potential applications in both bioimaging and the combined use of phyto-photothermal therapy for cancer treatment.

Keywords: bioactive liposome, hyptis suaveolens, photothermal therapy, lung cancer

Procedia PDF Downloads 53

Authors: Chris J. Boreham, Dianne S. Edwards, Amber Jarrett, Justin Davies, Robert Poreda, Alex Sessions, John Eiler

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The origins of natural gases in the Amadeus Basin have been assessed using molecular and stable isotope (C, H, N, He) systematics. A dominant end-member thermogenic, oil-associated gas is considered for the Ordovician Pacoota−Stairway sandstones of the Mereenie gas and oil field. In addition, an abiogenic end-member is identified in the latest Proterozoic lower Arumbera Sandstone of the Dingo gasfield, being most likely associated with radiolysis of methane with polymerisation to wet gases. The latter source assignment is based on a similar geochemical fingerprint derived from the laboratory gamma irradiation experiments on methane. A mixed gas source is considered for the Palm Valley gasfield in the Ordovician Pacoota Sandstone. Gas wetness (%∑C₂−C₅/∑C₁−C₅) decreases in the order Mereenie (19.1%) > Palm Valley (9.4%) > Dingo (4.1%). Non-produced gases at Magee-1 (23.5%; Late Proterozoic Heavitree Quartzite) and Mount Kitty-1 (18.9%; Paleo-Mesoproterozoic fractured granitoid basement) are very wet. Methane thermometry based on clumped isotopes of methane (¹³CDH₃) is consistent with the abiogenic origin for the Dingo gas field with methane formation temperature of 254ᵒC. However, the low methane formation temperature of 57°C for the Mereenie gas suggests either a mixed thermogenic-biogenic methane source or there is no thermodynamic equilibrium between the methane isotopomers. The shallow reservoir depth and present-day formation temperature below 80ᵒC would support microbial methanogenesis, but there is no accompanying alteration of the C- and H-isotopes of the wet gases and CO₂ that is typically associated with biodegradation. The Amadeus Basin gases show low to extremely high inorganic gas contents. Carbon dioxide is low in abundance (< 1% CO₂) and becomes increasing depleted in ¹³C from the Palm Valley (av. δ¹³C 0‰) to the Mereenie (av. δ¹³C -6.6‰) and Dingo (av. δ¹³C -14.3‰) gas fields. Although the wide range in carbon isotopes for CO₂ is consistent with multiple origins from inorganic to organic inputs, the most likely process is fluid-rock alteration with enrichment in ¹²C in the residual gaseous CO₂ accompanying progressive carbonate precipitation within the reservoir. Nitrogen ranges from low−moderate (1.7−9.9% N₂) abundance (Palm Valley av. 1.8%; Mereenie av. 9.1%; Dingo av. 9.4%) to extremely high abundance in Magee-1 (43.6%) and Mount Kitty-1 (61.0%). The nitrogen isotopes for the production gases have δ¹⁵N = -3.0‰ for Mereenie, -3.0‰ for Palm Valley and -7.1‰ for Dingo, suggest all being mixed inorganic and thermogenic nitrogen sources. Helium (He) abundance varies over a wide range from a low of 0.17% to one of the world’s highest at 9% (Mereenie av. 0.23%; Palm Valley av. 0.48%, Dingo av. 0.18%, Magee-1 6.2%; Mount Kitty-1 9.0%). Complementary helium isotopes (R/Ra = ³He/⁴Hesample / ³He/⁴Heair) range from 0.013 to 0.031 R/Ra, indicating a dominant crustal origin for helium with a sustained input of radiogenic 4He from the decomposition of U- and Th-bearing minerals, effectively diluting any original mantle helium input. The high helium content in the non-produced gases compared to the shallower producing wells most likely reflects their stratigraphic position relative to the Tonian Bitter Springs Group with the former below and the latter above an effective carbonate-salt seal.

Keywords: amadeus gas, thermogenic, abiogenic, C, H, N, He isotopes

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Authors: Kuan Lun Pan, Moo Been Chang

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Volatile organic compounds (VOCs) are one of major air contaminants, and they can react with nitrogen oxides (NOx) in atmosphere to form ozone (O3) and peroxyacetyl nitrate (PAN) with solar irradiation, leading to environmental hazards. In addition, some VOCs are toxic at low concentration levels and cause adverse effects on human health. How to effectively reduce VOCs emission has become an important issue. Thermal catalysis is regarded as an effective way for VOCs removal because it provides oxidation route to successfully convert VOCs into carbon dioxide (CO2) and water (H2O(g)). Single perovskite-type catalysts are promising for VOC removal, and they are of good potential to replace noble metals due to good activity and high thermal stability. Single perovskites can be generally described as ABO3 or A2BO4, where A-site is often a rare earth element or an alkaline. Typically, the B-site is transition metal cation (Fe, Cu, Ni, Co, or Mn). Catalytic properties of perovskites mainly rely on nature, oxidation states and arrangement of B-site cation. Interestingly, single perovskites could be further synthesized to form double perovskite-type catalysts which can simply be represented by A2B’B”O6. Likewise, A-site stands for an alkaline metal or rare earth element, and the B′ and B′′ are transition metals. Double perovskites possess unique surface properties. In structure, three-dimensional of B-site with ordered arrangement of B’O6 and B”O6 is presented alternately, and they corner-share octahedral along three directions of the crystal lattice, while cations of A-site position between the void of octahedral. It has attracted considerable attention due to specific arrangement of alternating B-site structure. Therefore, double perovskites may have more variations than single perovskites, and this greater variation may promote catalytic performance. It is expected that activity of double perovskites is higher than that of single perovskites toward VOC removal. In this study, double perovskite-type catalyst (La2CoMnO6) is prepared and evaluated for VOC removal. Also, single perovskites including LaCoO3 and LaMnO3 are tested for the comparison purpose. Toluene (C7H8) is one of the important VOCs which are commonly applied in chemical processes. In addition to its wide application, C7H8 has high toxicity at a low concentration. Therefore, C7H8 is selected as the target compound in this study. Experimental results indicate that double perovskite (La2CoMnO6) has better activity if compared with single perovskites. Especially, C7H8 can be completely oxidized to CO2 at 300oC as La2CoMnO6 is applied. Characterization of catalysts indicates that double perovskite has unique surface properties and is of higher amounts of lattice oxygen, leading to higher activity. For durability test, La2CoMnO6 maintains high C7H8 removal efficiency of 100% at 300oC and 30,000 h-1, and it also shows good resistance to CO2 (5%) and H2O(g) (5%) of gas streams tested. For various VOCs including isopropyl alcohol (C3H8O), ethanal (C2H4O), and ethylene (C2H4) tested, as high as 100% efficiency could be achieved with double perovskite-type catalyst operated at 300℃, indicating that double perovskites are promising catalysts for VOCs removal, and possible mechanisms will be elucidated in this paper.

Keywords: volatile organic compounds, Toluene (C7H8), double perovskite-type catalyst, catalysis

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Authors: Asmat Nawaz, Ceylan Zafer, Ali K. Erdinc, Kaiying Wang, M. Nadeem Akram

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Hybrid halide Perovskites with the general formula ABX₃, where X = Cl, Br or I, are considered as an ideal candidates for the preparation of photovoltaic devices. The most commonly and successfully used hybrid halide perovskite for photovoltaic applications is CH₃NH₃PbI₃ and its analogue prepared from lead chloride, commonly symbolized as CH₃NH₃PbI₃_ₓClₓ. Some researcher groups are using lead free (Sn replaces Pb) and mixed halide perovskites for the fabrication of the devices. Both mesoporous and planar structures have been developed. By Comparing mesoporous structure in which the perovskite materials infiltrate into mesoporous metal oxide scaffold, the planar architecture is much simpler and easy for device fabrication. In a typical perovskite solar cell, a perovskite absorber layer is sandwiched between the hole and electron transport. Upon the irradiation, carriers are created in the absorber layer that can travel through hole and electron transport layers and the interface in between. We fabricated inverted planar heterojunction structure ITO/PEDOT/ Perovskite/PCBM/Al, based solar cell via two-step spin coating method. This is also called Sequential deposition method. A small amount of cheap additive H₂O was added into PbI₂/DMF to make a homogeneous solution. We prepared four different solution such as (W/O H₂O, 1% H₂O, 2% H₂O, 3% H₂O). After preparing, the whole night stirring at 60℃ is essential for the homogenous precursor solutions. We observed that the solution with 1% H₂O was much more homogenous at room temperature as compared to others. The solution with 3% H₂O was precipitated at once at room temperature. The four different films of PbI₂ were formed on PEDOT substrates by spin coating and after that immediately (before drying the PbI₂) the substrates were immersed in the methyl ammonium iodide solution (prepared in isopropanol) for the completion of the desired perovskite film. After getting desired films, rinse the substrates with isopropanol to remove the excess amount of methyl ammonium iodide and finally dried it on hot plate only for 1-2 minutes. In this study, we added H₂O in the PbI₂/DMF precursor solution. The concept of additive is widely used in the bulk- heterojunction solar cells to manipulate the surface morphology, leading to the enhancement of the photovoltaic performance. There are two most important parameters for the selection of additives. (a) Higher boiling point w.r.t host material (b) good interaction with the precursor materials. We observed that the morphology of the films was improved and we achieved a denser, uniform with less cavities and almost full surface coverage films but only using precursor solution having 1% H₂O. Therefore, we fabricated the complete perovskite solar cell by sequential deposition technique with precursor solution having 1% H₂O. We concluded that with the addition of additives in the precursor solutions one can easily be manipulate the morphology of the perovskite film. In the sequential deposition method, thickness of perovskite film is in µm and the charge diffusion length of PbI₂ is in nm. Therefore, by controlling the thickness using other deposition methods for the fabrication of solar cells, we can achieve the better efficiency.

Keywords: methylammonium lead iodide, perovskite solar cell, precursor composition, sequential deposition

Procedia PDF Downloads 212

Authors: Taboka Motlhabane, Pradeep Sahoo

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The global demand for cooling has grown exponentially over the past century to meet economic development and social needs, accounting for approximately 10% of the global electricity consumption. As global temperatures continue to rise, the demand for cooling and heating, ventilation and air-conditioning (HVAC) equipment is set to rise with it. The increased use of HVAC equipment has significantly contributed to the growth of greenhouse gas (GHG) emissions which aid the climate crisis- one of the biggest challenges faced by the current generation. The need to address emissions caused directly by HVAC equipment and electricity generated to meet the cooling or heating demand is ever more pressing. Currently, developed countries account for the largest cooling and heating demand, however developing countries are anticipated to experience a huge increase in population growth in 10 years, resulting in a shift in energy demand. Developing countries, which are projected to account for nearly 60% of the world's GDP by 2030, are rapidly building infrastructure and economies to meet their growing needs and meet these projections. Cooling, a very energy-intensive process that can account for 20 % to 75% of a building's energy, depending on the building's use. Solar photovoltaic (PV) driven air-conditioning offers a great cost-effective alternative for adoption in both residential and non-residential buildings to offset grid electricity, particularly in countries with high irradiation, such as Botswana. This research paper explores the potential of a grid-connected solar photovoltaic vapor-compression air-conditioning system for the Peter-Smith herbarium at the Okavango Research Institute (ORI) University of Botswana campus in Maun, Botswana. The herbarium plays a critical role in the collection and preservation of botanical data, dating back over 100 years, with pristine collection from the Okavango Delta, a UNESCO world heritage site and serves as a reference and research site. Due to the herbarium’s specific needs, it operates throughout the day and year in an attempt to maintain a constant herbarium temperature of 16°?. The herbarium model studied simulates a variable-air-volume HVAC system with a system rating of 30 kW. Simulation results show that the HVAC system accounts for 68.9% of the building's total electricity at 296 509.60 kWh annually. To offset the grid electricity, a 175.1 kWp nominal power rated PV system requiring 416 modules to match the required power, covering an area of 928 m2 is used to meet the HVAC system annual needs. An economic assessment using PVsyst found that for an installation priced with average solar PV prices in Botswana totalled to be 787 090.00 BWP, with annual operating costs of 30 500 BWP/year. With self-project financing, the project is estimated to have recouped its initial investment within 6.7 years. At an estimated project lifetime of 20 years, the Net Present Value is projected at 1 565 687.00 BWP with a ROI of 198.9%, with 74 070.67 tons of CO2 saved at the end of the project lifetime. This study investigates the performance of the HVAC system to meet the indoor air comfort requirements, the annual PV system performance, and the building model has been simulated using DesignBuilder Software.

Keywords: vapor compression refrigeration, solar cooling, renewable energy, herbarium

Procedia PDF Downloads 101

Authors: S. Thomet, S. De-Paoli, F. Ghaffari, J. M. Daveau, P. Roche, O. Romain

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In this paper, we present a hardware module dedicated to understanding the fail reason of a System on Chip (SoC) exposed to a particle beam. Impact of Single-Event Effects (SEE) on processor-based SoCs is a concern that has increased in the past decade, particularly for terrestrial applications with automotive safety increasing requirements, as well as consumer and industrial domains. The SEE created by the impact of a particle on an SoC may have consequences that can end to instability or crashes. Specific hardening techniques for hardware and software have been developed to make such systems more reliable. SoC is then qualified using cosmic ray Accelerated Soft-Error Rate (ASER) to ensure the Soft-Error Rate (SER) remains in mission profiles. Understanding where errors are occurring is another challenge because of the complexity of operations performed in an SoC. Common techniques to monitor an SoC running under a beam are based on non-intrusive debug, consisting of recording the program counter and doing some consistency checking on the fly. To detect and understand SEE, we have developed a module embedded within the SoC that provide support for recording probes, hardware watchpoints, and a memory mapped register bank dedicated to software usage. To identify CPU failure modes and the most important resources to probe, we have carried out a fault injection campaign on the RTL model of the SoC. Probes are placed on generic CPU registers and bus accesses. They highlight the propagation of errors and allow identifying the failure modes. Typical resulting errors are bit-flips in resources creating bad addresses, illegal instructions, longer than expected loops, or incorrect bus accesses. Although our module is processor agnostic, it has been interfaced to a RISC-V by probing some of the processor registers. Probes are then recorded in a ring buffer. Associated hardware watchpoints are allowing to do some control, such as start or stop event recording or halt the processor. Finally, the module is also providing a bank of registers where the firmware running on the SoC can log information. Typical usage is for operating system context switch recording. The module is connected to a dedicated debug bus and is interfaced to a remote controller via a debugger link. Thus, a remote controller can interact with the monitoring module without any intrusiveness on the SoC. Moreover, in case of CPU unresponsiveness, or system-bus stall, the recorded information can still be recovered, providing the fail reason. A preliminary version of the module has been integrated into a test chip currently being manufactured at ST in 28-nm FDSOI technology. The module has been triplicated to provide reliable information on the SoC behavior. As the primary application domain is automotive and safety, the efficiency of the module will be evaluated by exposing the test chip under a fast-neutron beam by the end of the year. In the meantime, it will be tested with alpha particles and electromagnetic fault injection (EMFI). We will report in the paper on fault-injection results as well as irradiation results.

Keywords: fault injection, SoC fail reason, SoC soft error rate, terrestrial application

Procedia PDF Downloads 199

Authors: Sree Bash Chandra Debnath, Didier Tonneau, Carole Fauquet, Agnes Tallet, Julien Darreon

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Purpose: Inorganic scintillating dosimetry is the most recent promising technique to solve several dosimetric issues and provide quality assurance in radiation therapy. Despite several advantages, the major issue of using scintillating detectors is the Cerenkov effect, typically induced in the visible emission range. In this context, the purpose of this research work is to evaluate the performance of a novel infrared inorganic scintillator detector (IR-ISD) in the radiation therapy treatment to ensure Cerenkov free signal and the best matches between the delivered and prescribed doses during treatment. Methods: A simple and small-scale infrared inorganic scintillating detector of 100 µm diameter with a sensitive scintillating volume of 2x10-6 mm3 was developed. A prototype of the dose verification system has been introduced based on PTIR1470/F (provided by Phosphor Technology®) material used in the proposed novel IR-ISD. The detector was tested on an Elekta LINAC system tuned at 6 MV/15MV and a brachytherapy source (Ir-192) used in the patient treatment protocol. The associated dose rate was measured in count rate (photons/s) using a highly sensitive photon counter (sensitivity ~20ph/s). Overall measurements were performed in IBATM water tank phantoms by following international Technical Reports series recommendations (TRS 381) for radiotherapy and TG43U1 recommendations for brachytherapy. The performance of the detector was tested through several dosimetric parameters such as PDD, beam profiling, Cerenkov measurement, dose linearity, dose rate linearity repeatability, and scintillator stability. Finally, a comparative study is also shown using a reference microdiamond dosimeter, Monte-Carlo (MC) simulation, and data from recent literature. Results: This study is highlighting the complete removal of the Cerenkov effect especially for small field radiation beam characterization. The detector provides an entire linear response with the dose in the 4cGy to 800 cGy range, independently of the field size selected from 5 x 5 cm² down to 0.5 x 0.5 cm². A perfect repeatability (0.2 % variation from average) with day-to-day reproducibility (0.3% variation) was observed. Measurements demonstrated that ISD has superlinear behavior with dose rate (R2=1) varying from 50 cGy/s to 1000 cGy/s. PDD profiles obtained in water present identical behavior with a build-up maximum depth dose at 15 mm for different small fields irradiation. A low dimension of 0.5 x 0.5 cm² field profiles have been characterized, and the field cross profile presents a Gaussian-like shape. The standard deviation (1σ) of the scintillating signal remains within 0.02% while having a very low convolution effect, thanks to lower sensitive volume. Finally, during brachytherapy, a comparison with MC simulations shows that considering energy dependency, measurement agrees within 0.8% till 0.2 cm source to detector distance. Conclusion: The proposed scintillating detector in this study shows no- Cerenkov radiation and efficient performance for several radiation therapy measurement parameters. Therefore, it is anticipated that the IR-ISD system can be promoted to validate with direct clinical investigations, such as appropriate dose verification and quality control in the Treatment Planning System (TPS).

Keywords: IR-Scintillating detector, dose measurement, micro-scintillators, Cerenkov effect

Procedia PDF Downloads 153

Authors: Pomozova Kseniia, Gorlachev Gennadiy, Chernyaev Aleksandr, Golanov Andrey

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In clinical practice, and especially in stereotactic radiosurgery planning, the significance of diffusion-weighted imaging (DWI) is growing. This makes the existence of software capable of quickly processing and reliably visualizing diffusion data, as well as equipped with tools for their analysis in terms of different tasks. We are developing the «MRDiffusionImaging» software on the standard C++ language. The subject part has been moved to separate class libraries and can be used on various platforms. The user interface is Windows WPF (Windows Presentation Foundation), which is a technology for managing Windows applications with access to all components of the .NET 5 or .NET Framework platform ecosystem. One of the important features is the use of a declarative markup language, XAML (eXtensible Application Markup Language), with which you can conveniently create, initialize and set properties of objects with hierarchical relationships. Graphics are generated using the DirectX environment. The MRDiffusionImaging software package has been implemented for processing diffusion magnetic resonance imaging (dMRI), which allows loading and viewing images sorted by series. An algorithm for "masking" dMRI series based on T2-weighted images was developed using a deformable surface model to exclude tissues that are not related to the area of interest from the analysis. An algorithm of distortion correction using deformable image registration based on autocorrelation of local structure has been developed. Maximum voxel dimension was 1,03 ± 0,12 mm. In an elementary brain's volume, the diffusion tensor is geometrically interpreted using an ellipsoid, which is an isosurface of the probability density of a molecule's diffusion. For the first time, non-parametric intensity distributions, neighborhood correlations, and inhomogeneities are combined in one segmentation of white matter (WM), grey matter (GM), and cerebrospinal fluid (CSF) algorithm. A tool for calculating the coefficient of average diffusion and fractional anisotropy has been created, on the basis of which it is possible to build quantitative maps for solving various clinical problems. Functionality has been created that allows clustering and segmenting images to individualize the clinical volume of radiation treatment and further assess the response (Median Dice Score = 0.963 ± 0,137). White matter tracts of the brain were visualized using two algorithms: deterministic (fiber assignment by continuous tracking) and probabilistic using the Hough transform. The proposed algorithms test candidate curves in the voxel, assigning to each one a score computed from the diffusion data, and then selects the curves with the highest scores as the potential anatomical connections. White matter fibers were visualized using a Hough transform tractography algorithm. In the context of functional radiosurgery, it is possible to reduce the irradiation volume of the internal capsule receiving 12 Gy from 0,402 cc to 0,254 cc. The «MRDiffusionImaging» will improve the efficiency and accuracy of diagnostics and stereotactic radiotherapy of intracranial pathology. We develop software with integrated, intuitive support for processing, analysis, and inclusion in the process of radiotherapy planning and evaluating its results.

Keywords: diffusion-weighted imaging, medical imaging, stereotactic radiosurgery, tractography

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Authors: Elvin P. Chizenga, Heidi Abrahamse

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Cancer cell resistance to therapy is the main cause of treatment failures and the poor prognosis of cancer convalescence. The progression of cervical cancer to other parts of the genitourinary system and the reported recurrence rates are overwhelming. Current treatments, including surgery, chemo and radiation have been inefficient in eradicating the tumor cells. These treatments are also associated with poor prognosis and reduced quality of life, including fertility loss. This has inspired the need for the development of new treatment modalities to eradicate cervical cancer successfully. Photodynamic Therapy (PDT) is a modern treatment modality that induces cell death by photochemical interactions of light and a photosensitizer, which in the presence of molecular oxygen, yields a set of chemical reactions that generate Reactive Oxygen Species (ROS) and other free radical species causing cell damage. Enhancing PDT using modified drug delivery can increase the concentration of the photosensitizer in the tumor cells, and this has the potential to maximize its therapeutic efficacy. In cervical cancer, all infected cells constitutively express genes of the E6 and E7 HPV viral oncoproteins, resulting in high concentrations of E6 and E7 in the cytoplasm. This provides an opportunity for active targeting of cervical cancer cells using immune-mediated drug delivery to maximize therapeutic efficacy. The use of nanoparticles in PDT has also proven effective in enhancing therapeutic efficacy. Gold nanoparticles (AuNps) in particular, are explored for their use in biomedicine due to their biocompatibility, low toxicity, and enhancement of drug uptake by tumor cells. In this present study, a biomolecule comprising of AuNPs, anti-E6 monoclonal antibodies, and Aluminium Phthalocyanine photosensitizer was synthesized for use in targeted PDT of cervical cancer. The AuNp-Anti-E6-Sulfonated Aluminium Phthalocyanine mix (AlPcSmix) photosensitizing biomolecule was synthesized by coupling AuNps and anti-E6 monoclonal antibodies to the AlPcSmix via Polyethylene Glycol (PEG) chemical links. The final product was characterized using Transmission Electron Microscope (TEM), Zeta Potential, Uv-Vis Spectrophotometry, Fourier Transform Infrared Spectroscopy (FTIR), and X-ray diffraction (XRD), to confirm its chemical structure and functionality. To observe its therapeutic role in treating cervical cancer, cervical cancer cells, HeLa cells were seeded in 3.4 cm² diameter culture dishes at a concentration of 5x10⁵ cells/ml, in vitro. The cells were treated with varying concentrations of the photosensitizing biomolecule and irradiated using a 673.2 nm wavelength of laser light. Post irradiation cellular responses were performed to observe changes in morphology, viability, proliferation, cytotoxicity, and cell death pathways induced. Dose-Dependent response of the cells to treatment was demonstrated as significant morphologic changes, increased cytotoxicity, and decreased cell viability and proliferation This study presented a synthetic biomolecule for targeted PDT of cervical cancer. The study suggested that PDT using this AuNp- Anti-E6- AlPcSmix photosensitizing biomolecule is a very effective treatment method for the eradication of cervical cancer cells, in vitro. Further studies in vivo need to be conducted to support the use of this biomolecule in treating cervical cancer in clinical settings.

Keywords: anti-E6 monoclonal antibody, cervical cancer, gold nanoparticles, photodynamic therapy

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Authors: Mazaher Yarmohamadi-Vasel, Ali Reza Modarresi-Alama, Sahar Shabzendedara

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Purpose/Objectives: The first purpose was synthesize Poly(N-(sulfophenyl)aniline) nanoflowers (PSANFLs) and Poly(N-(sulfophenyl)aniline) nanofibers/titanium dioxide nanoparticles ((PSANFs/TiO2NPs) by a solid-state mechano-chemical reaction and template-free method and use them in hybrid solar cell. Also, our second aim was to increase the solubility and the processability of conjugated nanomaterials in water through polar functionalized materials. poly[N-(4-sulfophenyl)aniline] is easily soluble in water because of the presence of polar groups of sulfonic acid in the polymer chain. Materials/Methods: Iron (III) chloride hexahydrate (FeCl3∙6H2O) were bought from Merck Millipore Company. Titanium oxide nanoparticles (TiO2, <20 nm, anatase) and Sodium diphenylamine-4-sulfonate (99%) were bought from Sigma-Aldrich Company. Titanium dioxide nanoparticles paste (PST-20T) was prepared from Sharifsolar Co. Conductive glasses coated with indium tin oxide (ITO) were bought from Xinyan Technology Co (China). For the first time we used the solid-state mechano-chemical reaction and template-free method to synthesize Poly(N-(sulfophenyl)aniline) nanoflowers. Moreover, for the first time we used the same technique to synthesize nanocomposite of Poly(N-(sulfophenyl)aniline) nanofibers and titanium dioxide nanoparticles (PSANFs/TiO2NPs) also for the first time this nanocomposite was synthesized. Examining the results of electrochemical calculations energy gap obtained by CV curves and UV–vis spectra demonstrate that PSANFs/TiO2NPs nanocomposite is a p-n type material that can be used in photovoltaic cells. Doctor blade method was used to creat films for three kinds of hybrid solar cells in terms of different patterns like ITO│TiO2NPs│Semiconductor sample│Al. In the following, hybrid photovoltaic cells in bilayer and bulk heterojunction structures were fabricated as ITO│TiO2NPs│PSANFLs│Al and ITO│TiO2NPs│PSANFs /TiO2NPs│Al, respectively. Fourier-transform infrared spectra, field emission scanning electron microscopy (FE-SEM), ultraviolet-visible spectra, cyclic voltammetry (CV) and electrical conductivity were the analysis that used to characterize the synthesized samples. Results and Conclusions: FE-SEM images clearly demonstrate that the morphology of the synthesized samples are nanostructured (nanoflowers and nanofibers). Electrochemical calculations of band gap from CV curves demonstrated that the forbidden band gap of the PSANFLs and PSANFs/TiO2NPs nanocomposite are 2.95 and 2.23 eV, respectively. I–V characteristics of hybrid solar cells and their power conversion efficiency (PCE) under 100 mWcm−2 irradiation (AM 1.5 global conditions) were measured that The PCE of the samples were 0.30 and 0.62%, respectively. At the end, all the results of solar cell analysis were discussed. To sum up, PSANFLs and PSANFLs/TiO2NPs were successfully synthesized by an affordable and straightforward mechanochemical reaction in solid-state under the green condition. The solubility and processability of the synthesized compounds have been improved compared to the previous work. We successfully fabricated hybrid photovoltaic cells of synthesized semiconductor nanostructured polymers and TiO2NPs as different architectures. We believe that the synthesized compounds can open inventive pathways for the development of other Poly(N-(sulfophenyl)aniline based hybrid materials (nanocomposites) proper for preparing new generation solar cells.

Keywords: mechanochemical synthesis, PSANFLs, PSANFs/TiO2NPs, solar cell

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

Abstract:

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

Keywords: chitosan, magnesium nanoparticles, nanomedicine, photothermal therapy

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Authors: Dmitriy Berillo, Areej K. A. Al-Jwaid, Jonathan L. Caplin, Andrew Cundy, Irina Savina

Abstract:

Chlorophenols (CPs) are used as a precursor in the production of higher CPs and dyestuffs, and as a preservative. Contamination by CPs of the ground water is located in the range from 0.15-100mg/L. The EU has set maximum concentration limits for pesticides and their degradation products of 0.1μg/L and 0.5μg/L, respectively. People working in industries which produce textiles, leather products, domestic preservatives, and petrochemicals are most heavily exposed to CPs. The International Agency for Research on Cancers categorized CPs as potential human carcinogens. Existing multistep water purification processes for CPs such as hydrogenation, ion exchange, liquid-liquid extraction, adsorption by activated carbon, forward and inverse osmosis, electrolysis, sonochemistry, UV irradiation, and chemical oxidation are not always cost effective and can cause the formation of even more toxic or mutagenic derivatives. Bioremediation of CPs derivatives utilizing microorganisms results in 60 to 100% decontamination efficiency and the process is more environmentally-friendly compared with existing physico-chemical methods. Microorganisms immobilized onto a substrate show many advantages over free bacteria systems, such as higher biomass density, higher metabolic activity, and resistance to toxic chemicals. They also enable continuous operation, avoiding the requirement for biomass-liquid separation. The immobilized bacteria can be reused several times, which opens the opportunity for developing cost-effective processes for wastewater treatment. In this study, we develop a bioremediation system for CPs based on macroporous materials, which can be efficiently used for wastewater treatment. Conditions for the preparation of the macroporous material from specific bacterial strains (Pseudomonas mendocina and Rhodococus koreensis) were optimized. The concentration of bacterial cells was kept constant; the difference was only the type of cross-linking agents used e.g. glutaraldehyde, novel polymers, which were utilized at concentrations of 0.5 to 1.5%. SEM images and rheology analysis of the material indicated a monolithic macroporous structure. Phenol was chosen as a model system to optimize the function of the cryogel material and to estimate its enzymatic activity, since it is relatively less toxic and harmful compared to CPs. Several types of macroporous systems comprising live bacteria were prepared. The viability of the cross-linked bacteria was checked using Live/Dead BacLight kit and Laser Scanning Confocal Microscopy, which revealed the presence of viable bacteria with the novel cross-linkers, whereas the control material cross-linked with glutaraldehyde(GA), contained mostly dead cells. The bioreactors based on bacteria were used for phenol degradation in batch mode at an initial concentration of 50mg/L, pH 7.5 and a temperature of 30°C. Bacterial strains cross-linked with GA showed insignificant ability to degrade phenol and for one week only, but a combination of cross-linking agents illustrated higher stability, viability and the possibility to be reused for at least five weeks. Furthermore, conditions for CPs degradation will be optimized, and the chlorophenol degradation rates will be compared to those for phenol. This is a cutting-edge bioremediation approach, which allows the purification of waste water from sustainable compounds without a separation step to remove free planktonic bacteria. Acknowledgments: Dr. Berillo D. A. is very grateful to Individual Fellowship Marie Curie Program for funding of the research.

Keywords: bioremediation, cross-linking agents, cross-linked microbial cell, chlorophenol degradation

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Authors: Michael R. Shurin, Galina Shurin, Vladimir A. Kirichenko

Abstract:

Background. Visibility of hepatic malignancies is poor on non-contrast imaging for daily verification of liver malignancies prior to radiation therapy on MRI-guided Linear Accelerators (MR-Linac). Ferumoxytol® (Feraheme, AMAG Pharmaceuticals, Waltham, MA) is a SPION agent that is increasingly utilized off-label as hepatic MRI contrast. This agent has the advantage of providing a functional assessment of the liver based upon its uptake by hepatic Kupffer cells proportionate to vascular perfusion, resulting in strong T1, T2 and T2* relaxation effects and enhanced contrast of malignant tumors, which lack Kupffer cells. The latter characteristic has been recently utilized for MRI-guided radiotherapy planning with precision targeting of liver malignancies. However potential radiotoxicity of SPION has never been addressed for its safe use as an MRI-contrast agent during liver radiotherapy on MRI-Linac. This study defines the radiomodulating properties of SPIONs in vitro on human monocyte and macrophage cell lines exposed to 60Go gamma-rays within clinical radiotherapy dose range. Methods. Human monocyte and macrophages cell line in cultures were loaded with a clinically relevant concentration of Ferumoxytol (30µg/ml) for 2 and 24 h and irradiated to 3Gy, 5Gy and 10Gy. Cells were washed and cultured for additional 24 and 48 h prior to assessing their phenotypic activation by flow cytometry and function, including viability (Annexin V/PI assay), proliferation (MTT assay) and cytokine expression (Luminex assay). Results. Our results reveled that SPION affected both human monocytes and macrophages in vitro. Specifically, iron oxide nanoparticles decreased radiation-induced apoptosis and prevented radiation-induced inhibition of human monocyte proliferative activity. Furthermore, Ferumoxytol protected monocytes from radiation-induced modulation of phenotype. For instance, while irradiation decreased polarization of monocytes to CD11b+CD14+ and CD11bnegCD14neg phenotype, Ferumoxytol prevented these effects. In macrophages, Ferumoxytol counteracted the ability of radiation to up-regulate cell polarization to CD11b+CD14+ phenotype and prevented radiation-induced down-regulation of expression of HLA-DR and CD86 molecules. Finally, Ferumoxytol uptake by human monocytes down-regulated expression of pro-inflammatory chemokines MIP-1α (Macrophage inflammatory protein 1α), MIP-1β (CCL4) and RANTES (CCL5). In macrophages, Ferumoxytol reversed the expression of IL-1RA, IL-8, IP-10 (CXCL10) and TNF-α, and up-regulates expression of MCP-1 (CCL2) and MIP-1α in irradiated macrophages. Conclusion. SPION agent Ferumoxytol increases resistance of human monocytes to radiation-induced cell death in vitro and supports anti-inflammatory phenotype of human macrophages under radiation. The effect is radiation dose-dependent and depends on the duration of Feraheme uptake. This study also finds strong evidence that SPIONs reversed the effect of radiation on the expression of pro-inflammatory cytokines involved in initiation and development of radiation-induced liver damage. Correlative translational work at our institution will directly assess the cyto-protective effects of Ferumoxytol on human Kupfer cells in vitro and ex vivo analysis of explanted liver specimens in a subset of patients receiving Feraheme-enhanced MRI-guided radiotherapy to the primary liver tumors as a bridge to liver transplant.

Keywords: superparamagnetic iron oxide nanoparticles, radioprotection, magnetic resonance imaging, liver

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Authors: Irina Alexandra Paun, Mona Mihailescu, Marian Zamfirescu, Catalin Romeo Luculescu, Adriana Maria Acasandrei, Cosmin Catalin Mustaciosu, Roxana Cristina Popescu, Maria Dinescu

Abstract:

A major concern in bone tissue engineering is to develop complex 3D architectures that mimic the natural cells environment, facilitate the cells growth in a defined manner and allow the flow transport of nutrients and metabolic waste. In particular, porous structures of controlled pore size and positioning are indispensable for growing human-like bone structures. Another concern is to monitor both the structures and the seeded cells with high spatial resolution and without interfering with the cells natural environment. The present approach relies on laser-based technologies employed for fabricating porous biomimetic structures that support the growth of osteoblast-like cells and for their non-invasive 3D imaging. Specifically, the porous structures were built by two photon polymerization –direct writing (2PP_DW) of the commercially available photoresists IL-L780, using the Photonic Professional 3D lithography system. The structures consist of vertical tubes with micrometer-sized heights and diameters, in a honeycomb-like spatial arrangement. These were fabricated by irradiating the IP-L780 photoresist with focused laser pulses with wavelength centered at 780 nm, 120 fs pulse duration and 80 MHz repetition rate. The samples were precisely scanned in 3D by piezo stages. The coarse positioning was done by XY motorized stages. The scanning path was programmed through a writing language (GWL) script developed by Nanoscribe. Following laser irradiation, the unexposed regions of the photoresist were washed out by immersing the samples in the Propylene Glycol Monomethyl Ether Acetate (PGMEA). The porous structures were seeded with osteoblast like MG-63 cells and their osteogenic potential was tested in vitro. The cell-seeded structures were analyzed in 3D using the digital holographic microscopy technique (DHM). DHM is a marker free and high spatial resolution imaging tool, where the hologram acquisition is performed non-invasively i.e. without interfering with the cells natural environment. Following hologram recording, a digital algorithm provided a 3D image of the sample, as well as information about its refractive index, which is correlated with the intracellular content. The axial resolution of the images went down to the nanoscale, while the temporal scales ranged from milliseconds up to hours. The hologram did not involve sample scanning and the whole image was available in one frame recorded going over 200μm field of view. The digital holograms processing provided 3D quantitative information on the porous structures and allowed a quantitative analysis of the cellular response in respect to the porous architectures. The cellular shape and dimensions were found to be influenced by the underlying micro relief. Furthermore, the intracellular content gave evidence on the beneficial role of the porous structures in promoting osteoblast differentiation. In all, the proposed laser-based protocol emerges as a promising tool for the fabrication and non-invasive imaging of porous constructs for bone tissue engineering. Acknowledgments: This work was supported by a grant of the Romanian Authority for Scientific Research and Innovation, CNCS-UEFISCDI, project PN-II-RU-TE-2014-4-2534 (contract 97 from 01/10/2015) and by UEFISCDI PN-II-PT-PCCA no. 6/2012. A part of this work was performed in the CETAL laser facility, supported by the National Program PN 16 47 - LAPLAS IV.

Keywords: biomimetic, holography, laser, osteoblast, two photon polymerization

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