Search results for: nano-scale microenvironment
183 On-Chip Aging Sensor Circuit Based on Phase Locked Loop Circuit
Authors: Ararat Khachatryan, Davit Mirzoyan
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In sub micrometer technology, the aging phenomenon starts to have a significant impact on the reliability of integrated circuits by bringing performance degradation. For that reason, it is important to have a capability to evaluate the aging effects accurately. This paper presents an accurate aging measurement approach based on phase-locked loop (PLL) and voltage-controlled oscillator (VCO) circuit. The architecture is rejecting the circuit self-aging effect from the characteristics of PLL, which is generating the frequency without any aging phenomena affects. The aging monitor is implemented in low power 32 nm CMOS technology, and occupies a pretty small area. Aging simulation results show that the proposed aging measurement circuit improves accuracy by about 2.8% at high temperature and 19.6% at high voltage.Keywords: aging effect, HCI, NBTI, nanoscale
Procedia PDF Downloads 359182 Impact of Fin Cross Section Shape on Potential Distribution of Nanoscale Trapezoidal FinFETs
Authors: Ahmed Nassim Moulai Khatir
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Fin field effect transistors (FinFETs) deliver superior levels of scalability than the classical structure of MOSFETs by offering the elimination of short channel effects. Modern FinFETs are 3D structures that rise above the planar substrate, but some of these structures have inclined surfaces, which results in trapezoidal cross sections instead of rectangular sections usually used. Fin cross section shape of FinFETs results in some device issues, like potential distribution performance. This work analyzes that impact with three-dimensional numeric simulation of several triple-gate FinFETs with various top and bottom widths of fin. Results of the simulation show that the potential distribution and the electrical field in the fin depend on the sidewall inclination angle.Keywords: FinFET, cross section shape, SILVACO, trapezoidal FinFETs
Procedia PDF Downloads 47181 GE as a Channel Material in P-Type MOSFETs
Authors: S. Slimani, B. Djellouli
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Novel materials and innovative device structures has become necessary for the future of CMOS. High mobility materials like Ge is a very promising material due to its high mobility and is being considered to replace Si in the channel to achieve higher drive currents and switching speeds .Various approaches to circumvent the scaling limits to benchmark the performance of nanoscale MOSFETS with different channel materials, the optimized structure is simulated within nextnano in order to highlight the quantum effects on DG MOSFETs when Si is replaced by Ge and SiO2 is replaced by ZrO2 and HfO2as the gate dielectric. The results have shown that Ge MOSFET have the highest mobility and high permittivity oxides serve to maintain high drive current. The simulations show significant improvements compared with DGMOSFET using SiO2 gate dielectric and Si channel.Keywords: high mobility, high-k, quantum effects, SOI-DGMOSFET
Procedia PDF Downloads 367180 Ancelim: Health System Restoration Protocol for Cancer Patients
Authors: Mark Berry
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A number of studies have identified several factors involved in the malignant progression of cancer cells. The Primary modulator in driving inflammation to these transformed cells has been identified as the transcription factor known as nuclear factor-κB. This essential regulator of inflammation and the development of cancer, combined with a microenvironment of inflammation and signaling molecules, plays a major role in the malignant progression of cancer, and this progression is the result of the mutagenic predisposition of persistent substances that combat infection at tumor sites and other areas of chronic inflammation. Inflammation-induced tumors, and their inflammatory cells and regulators may be the primary source of metastasis of tumor cells through angiogenesis. Previous research on cytokines and chemokines, including their downstream targets, has been the focus of the cancer/inflammation connection. The identification of the biological mechanisms of other proteins vital to the inflammation cascade and their interactions are crucial to novel and effective therapeutic protocols for the treatment of inflammation-induced cancers. The Ancelim HSRP Protocol is just such a therapeutic intervention.Keywords: ancelim, cancer, inflammation, tumor
Procedia PDF Downloads 545179 High Frequency Sonochemistry: A New Field of Cavitation‐Free Acoustic Materials Synthesis and Manipulation
Authors: Amgad Rezk, Heba Ahmed, Leslie Yeo
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Ultrasound presents a powerful means for material synthesis. In this talk, we showcase a new field demonstrating the possibility for harnessing sound energy sources at considerably higher frequencies (10 MHz to 1 GHz) compared to conventional ultrasound (kHz and up to ~2 MHz) for crystalising and manipulating a variety of nanoscale materials. At these frequencies, cavitation—which underpins most sonochemical processes—is largely absent, suggesting that altogether fundamentally different mechanisms are at dominant. Examples include the crystallization of highly oriented structures, quasi-2D metal-organic frameworks and nanocomposites. These fascinating examples reveal how the highly nonlinear electromechanical coupling associated with high-frequency surface vibration gives rise to molecular ordering and assembly on the nano and microscale.Keywords: high-frequency acoustics, microfluidics, crystallisation, composite nanomaterials
Procedia PDF Downloads 121178 Two-Dimensional WO₃ and TiO₂ Semiconductor Oxides Developed by Atomic Layer Deposition with Controllable Nano-Thickness on Wafer-Scale
Authors: S. Zhuiykov, Z. Wei
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Conformal defect-free two-dimensional (2D) WO₃ and TiO₂ semiconductors have been developed by the atomic layer deposition (ALD) technique on wafer scale with unique approach to the thickness control with precision of ± 10% from the monolayer of nanomaterial (less than 1.0 nm thick) to the nano-layered 2D structures with thickness of ~3.0-7.0 nm. Developed 2D nanostructures exhibited unique, distinguishable properties at nanoscale compare to their thicker counterparts. Specifically, 2D TiO₂-Au bilayer demonstrated improved photocatalytic degradation of palmitic acid under UV and visible light illumination. Improved functional capabilities of 2D semiconductors would be advantageous to various environmental, nano-energy and bio-sensing applications. The ALD-enabled approach is proven to be versatile, scalable and applicable to the broader range of 2D semiconductors.Keywords: two-dimensional (2D) semiconductors, ALD, WO₃, TiO₂, wafer scale
Procedia PDF Downloads 153177 Mathematical Modeling of Avascular Tumor Growth and Invasion
Authors: Meitham Amereh, Mohsen Akbari, Ben Nadler
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Cancer has been recognized as one of the most challenging problems in biology and medicine. Aggressive tumors are a lethal type of cancers characterized by high genomic instability, rapid progression, invasiveness, and therapeutic resistance. Their behavior involves complicated molecular biology and consequential dynamics. Although tremendous effort has been devoted to developing therapeutic approaches, there is still a huge need for new insights into the dark aspects of tumors. As one of the key requirements in better understanding the complex behavior of tumors, mathematical modeling and continuum physics, in particular, play a pivotal role. Mathematical modeling can provide a quantitative prediction on biological processes and help interpret complicated physiological interactions in tumors microenvironment. The pathophysiology of aggressive tumors is strongly affected by the extracellular cues such as stresses produced by mechanical forces between the tumor and the host tissue. During the tumor progression, the growing mass displaces the surrounding extracellular matrix (ECM), and due to the level of tissue stiffness, stress accumulates inside the tumor. The produced stress can influence the tumor by breaking adherent junctions. During this process, the tumor stops the rapid proliferation and begins to remodel its shape to preserve the homeostatic equilibrium state. To reach this, the tumor, in turn, upregulates epithelial to mesenchymal transit-inducing transcription factors (EMT-TFs). These EMT-TFs are involved in various signaling cascades, which are often associated with tumor invasiveness and malignancy. In this work, we modeled the tumor as a growing hyperplastic mass and investigated the effects of mechanical stress from surrounding ECM on tumor invasion. The invasion is modeled as volume-preserving inelastic evolution. In this framework, principal balance laws are considered for tumor mass, linear momentum, and diffusion of nutrients. Also, mechanical interactions between the tumor and ECM is modeled using Ciarlet constitutive strain energy function, and dissipation inequality is utilized to model the volumetric growth rate. System parameters, such as rate of nutrient uptake and cell proliferation, are obtained experimentally. To validate the model, human Glioblastoma multiforme (hGBM) tumor spheroids were incorporated inside Matrigel/Alginate composite hydrogel and was injected into a microfluidic chip to mimic the tumor’s natural microenvironment. The invasion structure was analyzed by imaging the spheroid over time. Also, the expression of transcriptional factors involved in invasion was measured by immune-staining the tumor. The volumetric growth, stress distribution, and inelastic evolution of tumors were predicted by the model. Results showed that the level of invasion is in direct correlation with the level of predicted stress within the tumor. Moreover, the invasion length measured by fluorescent imaging was shown to be related to the inelastic evolution of tumors obtained by the model.Keywords: cancer, invasion, mathematical modeling, microfluidic chip, tumor spheroids
Procedia PDF Downloads 111176 Evolution of Microstructure through Phase Separation via Spinodal Decomposition in Spinel Ferrite Thin Films
Authors: Nipa Debnath, Harinarayan Das, Takahiko Kawaguchi, Naonori Sakamoto, Kazuo Shinozaki, Hisao Suzuki, Naoki Wakiya
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Nowadays spinel ferrite magnetic thin films have drawn considerable attention due to their interesting magnetic and electrical properties with enhanced chemical and thermal stability. Spinel ferrite magnetic films can be implemented in magnetic data storage, sensors, and spin filters or microwave devices. It is well established that the structural, magnetic and transport properties of the magnetic thin films are dependent on microstructure. Spinodal decomposition (SD) is a phase separation process, whereby a material system is spontaneously separated into two phases with distinct compositions. The periodic microstructure is the characteristic feature of SD. Thus, SD can be exploited to control the microstructure at the nanoscale level. In bulk spinel ferrites having general formula, MₓFe₃₋ₓ O₄ (M= Co, Mn, Ni, Zn), phase separation via SD has been reported only for cobalt ferrite (CFO); however, long time post-annealing is required to occur the spinodal decomposition. We have found that SD occurs in CoF thin film without using any post-deposition annealing process if we apply magnetic field during thin film growth. Dynamic Aurora pulsed laser deposition (PLD) is a specially designed PLD system through which in-situ magnetic field (up to 2000 G) can be applied during thin film growth. The in-situ magnetic field suppresses the recombination of ions in the plume. In addition, the peak’s intensity of the ions in the spectra of the plume also increases when magnetic field is applied to the plume. As a result, ions with high kinetic energy strike into the substrate. Thus, ion-impingement occurred under magnetic field during thin film growth. The driving force of SD is the ion-impingement towards the substrates that is induced by in-situ magnetic field. In this study, we report about the occurrence of phase separation through SD and evolution of microstructure after phase separation in spinel ferrite thin films. The surface morphology of the phase separated films show checkerboard like domain structure. The cross-sectional microstructure of the phase separated films reveal columnar type phase separation. Herein, the decomposition wave propagates in lateral direction which has been confirmed from the lateral composition modulations in spinodally decomposed films. Large magnetic anisotropy has been found in spinodally decomposed nickel ferrite (NFO) thin films. This approach approves that magnetic field is also an important thermodynamic parameter to induce phase separation by the enhancement of up-hill diffusion in thin films. This thin film deposition technique could be a more efficient alternative for the fabrication of self-organized phase separated thin films and employed in controlling of the microstructure at nanoscale level.Keywords: Dynamic Aurora PLD, magnetic anisotropy, spinodal decomposition, spinel ferrite thin film
Procedia PDF Downloads 366175 Theoretical Analysis of Performance Parameters of a Microchannel Heat Exchanger
Authors: Shreyas Kotian, Nishant Jainm, Nachiket Methekar
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The increase in energy demands in various industrial sectors has called for devices small in size with high heat transfer rates. Microchannel heat exchangers (MCHX) have thus been studied and applied in various fields such as thermal engineering, aerospace engineering and nanoscale heat transfer. They have been a case of investigation due to their augmented thermal characteristics and low-pressure drop. The goal of the current investigation is to analyze the thermohydraulic performance of the heat exchanger analytically. Studies are done for various inlet conditions and flow conditions. At Thi of 90°C, the effectiveness increased by about 22% for an increase in Re from 1000 to 5000 of the cold fluid. It was also observed that at Re = 5000 for the hot fluid, the heat recovered by the hot fluid increases by about 69% for an increase in inlet temperature of the hot fluid from 50°C to 70°C.Keywords: theoretical analysis, performance parameters, microchannel heat exchanger, Reynolds number
Procedia PDF Downloads 152174 Stroma-Providing Activity of Adipose Derived Mesenchymal Stromal Cells in Tissue-Related O2 Microenvironment
Authors: P. I. Bobyleva, E. R. Andreeva, I. V. Andrianova, E. V. Maslova, L. B. Buravkova
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This work studied the ability of adipose tissue-derived mesenchymal stromal cells (MSCs) to form stroma for expansion of cord blood hematopoietic cells. We showed that 72-hour interaction of MSCs with cord blood mononuclear cells (MNCs) in vitro at atmospheric (20%) and low (5%) O2 conditions increased the expression of ICAM-1, HCAM (at the beginning of interaction) on MSCs. Viability of MSCs and MNCs were maintained at high level. Adhesion of MNCs to MSCs was faster at 20% O2. MSCs promoted the proliferation of adhered MNCs to form the suspension containing great number of hematopoietic colony-forming units, and this effect was more pronounced at 5% O2. Thus, adipose-derived MSCs supplied sufficient stromal support to cord blood MNCs both at 20% and 5% О2, providing their adhesion with further expansion of new generation of different hematopoietic lineages.Keywords: hematopoietic stem and progenitor cells, mesenchymal stromal cells, tissue-related oxygen, adipose tissue
Procedia PDF Downloads 418173 Structure and Properties of Intermetallic NiAl-Based Coatings Produced by Magnetron Sputtering Technique
Authors: Tatiana S. Ogneva
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Aluminum and nickel-based intermetallic compounds have attracted the attention of scientific community as promising materials for heat-resistant and wear-resistant coatings in such manufacturing areas as microelectronics, aircraft and rocket building and chemical industries. Magnetron sputtering makes possible to coat materials without formation of liquid phase and improves the mechanical and functional properties of nickel aluminides due to the possibility of nanoscale structure formation. The purpose of the study is the investigation of structure and properties of intermetallic coatings produced by magnetron sputtering technique. The feature of this work is the using of composite targets for sputtering, which were consisted of two semicircular sectors of cp-Ni and cp-Al. Plates of alumina, silicon, titanium and steel alloys were used as substrates. To estimate sputtering conditions on structure of intermetallic coatings, a series of samples were produced and studied in detail using scanning and transition electron microcopy and X-Ray diffraction. Besides, nanohardness and scratching tests were carried out. The varying parameters were the distance from the substrate to the target, the duration and the power of the sputtering. The thickness of the obtained intermetallic coatings varied from 0.05 to 0.5 mm depending on the sputtering conditions. The X-ray diffraction data indicated that the formation of intermetallic compounds occurred after sputtering without additional heat treatment. Sputtering at a distance not closer than 120 mm led to the formation of NiAl phase. Increase in the power of magnetron from 300 to 900 W promoted the increase of heterogeneity of the phase composition and the appearance of intermetallic phases NiAl, Ni₂Al₃, NiAl₃, and Al under the aluminum side, and NiAl, Ni₃Al, and Ni under the nickel side of the target. A similar trend is observed with increasing the distance of sputtering from 100 to 60 mm. The change in the phase composition correlates with the changing of the atomic composition of the coatings. Scanning electron microscopy revealed that the coatings have a nanoscale grain structure. In this case, the substrate material and the distance from the substrate to the magnetron have a significant effect on the structure formation process. The size of nanograins differs from 10 to 83 nm and depends not only on the sputtering modes but also on material of a substrate. Nanostructure of the material influences the level of mechanical properties. The highest level of nanohardness of the coatings deposited during 30 minutes on metallic substrates at a distance of 100 mm reached 12 GPa. It was shown that nanohardness depends on the grain size of the intermetallic compound. Scratching tests of the coatings showed a high level of adhesion of the coating to substrate without any delamination and cracking. The results of the study showed that magnetron sputtering of composite targets consisting of nickel and aluminum semicircles makes it possible to form intermetallic coatings with good mechanical properties directly in the process of sputtering without additional heat treatment.Keywords: intermetallic coatings, magnetron sputtering, mechanical properties, structure
Procedia PDF Downloads 121172 Dicarbonyl Methylglyoxal Induces Structural Perturbations, Aggregation and Immunogenicity in IgG with Implications in Auto-Immune Response in Diabetes
Authors: Sidra Islam, Moin Uddin, Mir A. Rouf
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A wide variety of pathological disorders owing to hyperglycemic conditions involves structural rearrangements and condensations of proteins. The implication of methylglyoxal (MG) modified immunoglobulin G (IgG) in the onset and progression of diabetes type 2 (T2DM) is studied in the present study. Using biophysical and biochemical approaches MG was found to perturb the structure of IgG, effect its microenvironment and leads to aggregate formation. Furthermore, MG-IgG was found to be highly immunogenic inducing high titre antibodies in female rabbits. Clinical studies revealed the presence of circulating anti-MG-IgG antibodies as analyzed by direct binding ELISA. The circulating auto antibodies were highly specific for MG-IgG as revealed by inhibition ELISA. Thus it can be concluded that MG is a powerful agent with a high damaging potential. To IgG. It is highly capable of generating immune response that contributes to the immunopathology associated with diabetes. Dicarbonyl adducts may emerge as potential biomarkers for T2DM.Keywords: immunogenicity, Immunoglobulin G, methylglyoxal, Type 2 Diabetes Mellitus
Procedia PDF Downloads 270171 An Approach for Modeling CMOS Gates
Authors: Spyridon Nikolaidis
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A modeling approach for CMOS gates is presented based on the use of the equivalent inverter. A new model for the inverter has been developed using a simplified transistor current model which incorporates the nanoscale effects for the planar technology. Parametric expressions for the output voltage are provided as well as the values of the output and supply current to be compatible with the CCS technology. The model is parametric according the input signal slew, output load, transistor widths, supply voltage, temperature and process. The transistor widths of the equivalent inverter are determined by HSPICE simulations and parametric expressions are developed for that using a fitting procedure. Results for the NAND gate shows that the proposed approach offers sufficient accuracy with an average error in propagation delay about 5%.Keywords: CMOS gate modeling, inverter modeling, transistor current mode, timing model
Procedia PDF Downloads 423170 Torsional Vibration of Carbon Nanotubes via Nonlocal Gradient Theories
Authors: Mustafa Arda, Metin Aydogdu
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Carbon nanotubes (CNTs) have many possible application areas because of their superior physical properties. Nonlocal Theory, which unlike the classical theories, includes the size dependency. Nonlocal Stress and Strain Gradient approaches can be used in nanoscale static and dynamic analysis. In the present study, torsional vibration of CNTs was investigated according to nonlocal stress and strain gradient theories. Effects of the small scale parameters to the non-dimensional frequency were obtained. Results were compared with the Molecular Dynamics Simulation and Lattice Dynamics. Strain Gradient Theory has shown more weakening effect on CNT according to the Stress Gradient Theory. Combination of both theories gives more acceptable results rather than the classical and stress or strain gradient theory according to Lattice Dynamics.Keywords: torsional vibration, carbon nanotubes, nonlocal gradient theory, stress, strain
Procedia PDF Downloads 389169 Electrospun Zinc Oxide Nanowires as Highly Sensitive Piezoelectric Transduction Elements for Nano-Scale Devices
Authors: K. Brince Paul, Nagendra Pratap Singh, Shiv Govind Singh, Siva Rama Krishna Vanjari
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In this paper, we report optimized procedure for synthesizing highly oriented, horizontally aligned, Zinc oxide (ZnO) nanowires targeted towards developing highly sensitive piezoelectric transduction elements. The synthesis was carried out using Electrospinning technique, a facile, robust, low cost technique for producing nanowires. The as-synthesized ZnO nanowires were characterized by X-ray powder diffraction (XRD), Field Emission scanning electron microscopy (FESEM) and Energy-dispersive X-ray spectroscopy (EDX).The Piezoelectric behavior of these nanowires was characterized using Peizoelectric Force microscopy (PFM). A very high d33 coefficient of 23.1 pm/V obtained through the PFM measurements is an indicative of its potential application towards developing miniaturized piezoelectric transduction elements for nanoscale devices.Keywords: electrospinning, piezoelectric, technique, zinc oxide
Procedia PDF Downloads 405168 Exploiting the Tumour Microenvironment in Order to Optimise Sonodynamic Therapy for Cancer
Authors: Maryam Mohammad Hadi, Heather Nesbitt, Hamzah Masood, Hashim Ahmed, Mark Emberton, John Callan, Alexander MacRobert, Anthony McHale, Nikolitsa Nomikou
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Sonodynamic therapy (SDT) utilises ultrasound in combination with sensitizers, such as porphyrins, for the production of cytotoxic reactive oxygen species (ROS) and the confined ablation of tumours. Ultrasound can be applied locally, and the acoustic waves, at frequencies between 0.5-2 MHz, are transmitted efficiently through tissue. SDT does not require highly toxic agents, and the cytotoxic effect only occurs upon ultrasound exposure at the site of the lesion. Therefore, this approach is not associated with adverse side effects. Further highlighting the benefits of SDT, no cancer cell population has shown resistance to therapy-triggered ROS production or their cytotoxic effects. This is particularly important, given the as yet unresolved issues of radiation and chemo-resistance, to the authors’ best knowledge. Another potential future benefit of this approach – considering its non-thermal mechanism of action – is its possible role as an adjuvant to immunotherapy. Substantial pre-clinical studies have demonstrated the efficacy and targeting capability of this therapeutic approach. However, SDT has yet to be fully characterised and appropriately exploited for the treatment of cancer. In this study, a formulation based on multistimulus-responsive sensitizer-containing nanoparticles that can accumulate in advanced prostate tumours and increase the therapeutic efficacy of SDT has been developed. The formulation is based on a polyglutamate-tyrosine (PGATyr) co-polymer carrying hematoporphyrin. The efficacy of SDT in this study was demonstrated using prostate cancer as the translational exemplar. The formulation was designed to respond to the microenvironment of advanced prostate tumours, such as the overexpression of the proteolytic enzymes, cathepsin-B and prostate-specific membrane antigen (PSMA), that can degrade the nanoparticles, reduce their size, improving both diffusions throughout the tumour mass and cellular uptake. The therapeutic modality was initially tested in vitro using LNCaP and PC3 cells as target cell lines. The SDT efficacy was also examined in vivo, using male SCID mice bearing LNCaP subcutaneous tumours. We have demonstrated that the PGATyr co-polymer is digested by cathepsin B and that digestion of the formulation by cathepsin-B, at tumour-mimicking conditions (acidic pH), leads to decreased nanoparticle size and subsequent increased cellular uptake. Sonodynamic treatment, at both normoxic and hypoxic conditions, demonstrated ultrasound-induced cytotoxic effects only for the nanoparticle-treated prostate cancer cells, while the toxicity of the formulation in the absence of ultrasound was minimal. Our in vivo studies in immunodeficient mice, using the hematoporphyrin-containing PGATyr nanoparticles for SDT, showed a 50% decrease in LNCaP tumour volumes within 24h, following IV administration of a single dose. No adverse effects were recorded, and body weight was stable. The results described in this study clearly demonstrate the promise of SDT to revolutionize cancer treatment. It emphasizes the potential of this therapeutic modality as a fist line treatment or in combination treatment for the elimination or downstaging of difficult to treat cancers, such as prostate, pancreatic, and advanced colorectal cancer.Keywords: sonodynamic therapy, nanoparticles, tumour ablation, ultrasound
Procedia PDF Downloads 138167 Artificial Intelligence Based Method in Identifying Tumour Infiltrating Lymphocytes of Triple Negative Breast Cancer
Authors: Nurkhairul Bariyah Baharun, Afzan Adam, Reena Rahayu Md Zin
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Tumor microenvironment (TME) in breast cancer is mainly composed of cancer cells, immune cells, and stromal cells. The interaction between cancer cells and their microenvironment plays an important role in tumor development, progression, and treatment response. The TME in breast cancer includes tumor-infiltrating lymphocytes (TILs) that are implicated in killing tumor cells. TILs can be found in tumor stroma (sTILs) and within the tumor (iTILs). TILs in triple negative breast cancer (TNBC) have been demonstrated to have prognostic and potentially predictive value. The international Immune-Oncology Biomarker Working Group (TIL-WG) had developed a guideline focus on the assessment of sTILs using hematoxylin and eosin (H&E)-stained slides. According to the guideline, the pathologists use “eye balling” method on the H&E stained- slide for sTILs assessment. This method has low precision, poor interobserver reproducibility, and is time-consuming for a comprehensive evaluation, besides only counted sTILs in their assessment. The TIL-WG has therefore recommended that any algorithm for computational assessment of TILs utilizing the guidelines provided to overcome the limitations of manual assessment, thus providing highly accurate and reliable TILs detection and classification for reproducible and quantitative measurement. This study is carried out to develop a TNBC digital whole slide image (WSI) dataset from H&E-stained slides and IHC (CD4+ and CD8+) stained slides. TNBC cases were retrieved from the database of the Department of Pathology, Hospital Canselor Tuanku Muhriz (HCTM). TNBC cases diagnosed between the year 2010 and 2021 with no history of other cancer and available block tissue were included in the study (n=58). Tissue blocks were sectioned approximately 4 µm for H&E and IHC stain. The H&E staining was performed according to a well-established protocol. Indirect IHC stain was also performed on the tissue sections using protocol from Diagnostic BioSystems PolyVue™ Plus Kit, USA. The slides were stained with rabbit monoclonal, CD8 antibody (SP16) and Rabbit monoclonal, CD4 antibody (EP204). The selected and quality-checked slides were then scanned using a high-resolution whole slide scanner (Pannoramic DESK II DW- slide scanner) to digitalize the tissue image with a pixel resolution of 20x magnification. A manual TILs (sTILs and iTILs) assessment was then carried out by the appointed pathologist (2 pathologists) for manual TILs scoring from the digital WSIs following the guideline developed by TIL-WG 2014, and the result displayed as the percentage of sTILs and iTILs per mm² stromal and tumour area on the tissue. Following this, we aimed to develop an automated digital image scoring framework that incorporates key elements of manual guidelines (including both sTILs and iTILs) using manually annotated data for robust and objective quantification of TILs in TNBC. From the study, we have developed a digital dataset of TNBC H&E and IHC (CD4+ and CD8+) stained slides. We hope that an automated based scoring method can provide quantitative and interpretable TILs scoring, which correlates with the manual pathologist-derived sTILs and iTILs scoring and thus has potential prognostic implications.Keywords: automated quantification, digital pathology, triple negative breast cancer, tumour infiltrating lymphocytes
Procedia PDF Downloads 116166 Catalytic Nanomaterials for Energy Conversion and Storage
Authors: Yijin Kang
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Chemical-electrical energy conversion and storage are greatly attractive for the development of sustainable energy. Catalytic processes are heavily involved in such energy conversion and storage. Development of high-performance catalyst nanomaterials relies on tuning material structures at nanoscale. This is in particular manifested in the design of catalysts demanding both high activity and durability. Here, a research system will be presented that connects fundamental investigation on well-defined extended surfaces (e.g. single crystal surfaces), extrapolation onto nanocrystals with highly controlled shape and size, exploration of interfacial interaction using novel nanocrystal superlattices as platform, and finally design of high performance catalysts in which all the possible beneficial properties from complex functional structures are implemented. Using recently published results, it will be demonstrated that optimal and fine balanced activity and durability, as well as tunable functionality, can be achieved by carefully tailoring the nanostructure of catalytic nanomaterials.Keywords: energy, nanomaterials, catalysis, electrocatalysis
Procedia PDF Downloads 235165 Investigation on Morphologies, Forming Mechanism, Photocatalytic and Electronic Properties of Co-Zn Ferrite Nanostructure Grown on the Reduced Graphene Oxide Support
Authors: Qinglei Liu, Ali Charkhesht, Tiva Sharifi, Ashkan Bahadoran
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Graphene sheets are promising nanoscale building blocks as a support material for the dispersion of nanoparticles. In this work, a solvothermal method employed to directly grow Co1-xZnxFe2O4 ferrite nanospheres on graphene oxide support that is subsequently reduced to graphene. The samples morphology, structure and crystallography were investigated using field-emission scanning electron microscopy (FE-SEM) and powder X-ray diffraction (XRD). The influences of the Zn2+ content on photocatalytic activity, electrical conductivity and magnetic property of the samples are also investigated. The results showed that Co1-x Znx Fe2 O4 nanoparticles are dispersed on graphene sheets and obtained nanocomposites are soft magnetic materials. In addition the samples showed excellent photocatalytic activity under visible light irradiation.Keywords: reduced graphene oxide, ferrite, magnetic nanocomposite, photocatalytic activity, solvothermal method
Procedia PDF Downloads 249164 Mechanical Properties of Carbon Nanofiber Reinforced Polymer Composites-Molecular Dynamics Approach
Authors: Sumit Sharma, Rakesh Chandra, Pramod Kumar, Navin Kumar
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Molecular dynamics (MD) simulation has been used to study the effect of carbon nanofiber (CNF) volume fraction (Vf) and aspect ratio (l/d) on mechanical properties of CNF reinforced polypropylene (PP) composites. Materials Studio 5.5 has been used as a tool for finding the modulus and damping in composites. CNF composition in PP was varied by volume from 0 to 16%. Aspect ratio of CNF was varied from l/d=5 to l/d=100. To the best of the knowledge of the authors, till date there is no study, either experimental or analytical, which predict damping for CNF-PP composites at the nanoscale. Hence, this will be a valuable addition in the area of nanocomposites. Results show that with only 2% addition by volume of CNF in PP, E11 increases 748%. Increase in E22 is very less in comparison to the increase in E11. With increase in CNF aspect ratio (l/d) till l/d=60, the longitudinal loss factor (η11) decreases rapidly. Results of this study have been compared with those available in literature.Keywords: carbon nanofiber, elasticity, mechanical properties, molecular dynamics
Procedia PDF Downloads 485163 Carbon Nanotubes (CNTs) as Multiplex Surface Enhanced Raman Scattering Sensing Platforms
Authors: Pola Goldberg Oppenheimer, Stephan Hofmann, Sumeet Mahajan
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Owing to its fingerprint molecular specificity and high sensitivity, surface-enhanced Raman scattering (SERS) is an established analytical tool for chemical and biological sensing capable of single-molecule detection. A strong Raman signal can be generated from SERS-active platforms given the analyte is within the enhanced plasmon field generated near a noble-metal nanostructured substrate. The key requirement for generating strong plasmon resonances to provide this electromagnetic enhancement is an appropriate metal surface roughness. Controlling nanoscale features for generating these regions of high electromagnetic enhancement, the so-called SERS ‘hot-spots’, is still a challenge. Significant advances have been made in SERS research, with wide-ranging techniques to generate substrates with tunable size and shape of the nanoscale roughness features. Nevertheless, the development and application of SERS has been inhibited by the irreproducibility and complexity of fabrication routes. The ability to generate straightforward, cost-effective, multiplex-able and addressable SERS substrates with high enhancements is of profound interest for miniaturised sensing devices. Carbon nanotubes (CNTs) have been concurrently, a topic of extensive research however, their applications for plasmonics has been only recently beginning to gain interest. CNTs can provide low-cost, large-active-area patternable substrates which, coupled with appropriate functionalization capable to provide advanced SERS-platforms. Herein, advanced methods to generate CNT-based SERS active detection platforms will be discussed. First, a novel electrohydrodynamic (EHD) lithographic technique will be introduced for patterning CNT-polymer composites, providing a straightforward, single-step approach for generating high-fidelity sub-micron-sized nanocomposite structures within which anisotropic CNTs are vertically aligned. The created structures are readily fine-tuned, which is an important requirement for optimizing SERS to obtain the highest enhancements with each of the EHD-CNTs individual structural units functioning as an isolated sensor. Further, gold-functionalized VACNTFs are fabricated as SERS micro-platforms. The dependence on the VACNTs’ diameters and density play an important role in the Raman signal strength, thus highlighting the importance of structural parameters, previously overlooked in designing and fabricating optimized CNTs-based SERS nanoprobes. VACNTs forests patterned into predesigned pillar structures are further utilized for multiplex detection of bio-analytes. Since CNTs exhibit electrical conductivity and unique adsorption properties, these are further harnessed in the development of novel chemical and bio-sensing platforms.Keywords: carbon nanotubes (CNTs), EHD patterning, SERS, vertically aligned carbon nanotube forests (VACNTF)
Procedia PDF Downloads 331162 Surface Sensing of Atomic Behavior of Polymer Nanofilms via Molecular Dynamics Simulation
Authors: Ling Dai
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Surface-sensing devices such as atomic force microscope have been widely used to characterize the surface structure and properties of nanoscale polymer films. However, using molecular dynamics simulations, we show that there is intrinsic and unavoidable inelastic deformation at polymer surfaces induced by the sensing tip. For linear chain polymers like perfluoropolyether, such tip-induced deformation derives from the differences in the atomic interactions which are atomic specie-based Van der Waals interactions, and resulting in atomic shuffling and causing inelastic alternation in both molecular structures and mechanical properties at the regions of the polymer surface. For those aromatic chain polymers like epoxy, the intrinsic deformation is depicted as the intra-chain rotation of aromatic rings and kinking of linear atomic connections. The present work highlights the need to reinterpret the data obtained from surface-sensing tests by considering this intrinsic inelastic deformation occurring at polymer surfaces.Keywords: polymer, surface, nano, molecular dynamics
Procedia PDF Downloads 356161 Study of Early Diagnosis of Oral Cancer by Non-invasive Saliva-On-Chip Device: A Microfluidic Approach
Authors: Ragini Verma, J. Ponmozhi
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The oral cavity is home to a wide variety of microorganisms that lead to various diseases and even oral cancer. Despite advancements in the diagnosis and detection at the initial phase, the situation hasn’t improved much. Saliva-on-a-chip is an innovative point-of-care platform for early diagnosis of oral cancer and other oral diseases in live and dead cells using a microfluidic device with a current perspective. Some of the major challenges, like real-time imaging of the oral cancer microbes, high throughput values, obtaining a high spatiotemporal resolution, etc. were faced by the scientific community. Integrated microfluidics and microscopy provide powerful approaches to studying the dynamics of oral pathology, microbe interaction, and the oral microenvironment. Here we have developed a saliva-on-chip (salivary microbes) device to monitor the effect on oral cancer. Adhesion of cancer-causing F. nucleatum; subsp. Nucleatum and Prevotella intermedia in the device was observed. We also observed a significant reduction in the oral cancer growth rate when mortality and morbidity were induced. These results show that this approach has the potential to transform the oral cancer and early diagnosis study.Keywords: microfluidic device, oral cancer microbes, early diagnosis, saliva-on-chip
Procedia PDF Downloads 101160 Effect of Plasticizer Additives on the Mechanical Properties of Cement Composite: A Molecular Dynamics Analysis
Authors: R. Mohan, V. Jadhav, A. Ahmed, J. Rivas, A. Kelkar
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Cementitious materials are an excellent example of a composite material with complex hierarchical features and random features that range from nanometer (nm) to millimeter (mm) scale. Multi-scale modeling of complex material systems requires starting from fundamental building blocks to capture the scale relevant features through associated computational models. In this paper, molecular dynamics (MD) modeling is employed to predict the effect of plasticizer additive on the mechanical properties of key hydrated cement constituent calcium-silicate-hydrate (CSH) at the molecular, nanometer scale level. Due to complexity, still unknown molecular configuration of CSH, a representative configuration widely accepted in the field of mineral Jennite is employed. The effectiveness of the Molecular Dynamics modeling to understand the predictive influence of material chemistry changes based on molecular/nanoscale models is demonstrated.Keywords: cement composite, mechanical properties, molecular dynamics, plasticizer additives
Procedia PDF Downloads 454159 Electrospun Nanofibrous Scaffolds Modified with Collagen-I and Fibronectin with LX-2 Cells to Study Liver Fibrosis in vitro
Authors: Prativa Das, Lay Poh Tan
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Three-dimensional microenvironment is a need to study the event cascades of liver fibrosis in vitro. Electrospun nanofibers modified with essential extracellular matrix proteins can closely mimic the random fibrous structure of native liver extracellular matrix (ECM). In this study, we fabricate a series of 3D electrospun scaffolds by wet electrospinning process modified with different ratios of collagen-I to fibronectin to achieve optimized distribution of these two ECM proteins on the fiber surface. A ratio of 3:1 of collagen-I to fibronectin was found to be optimum for surface modification of electrospun poly(lactic-co-glycolic acid) (PLGA) fibers by chemisorption process. In 3:1 collagen-I to fibronectin modified scaffolds the total protein content increased by ~2 fold compared to collagen-I modified and ~1.5 fold compared to 1:1/9:1 collagen-I to fibronectin modified scaffolds. We have cultured LX-2 cells on this scaffold over 14 days and found that LX-2 cells acquired more quiescent phenotype throughout the culture period and shown significantly lower expression of alpha smooth muscle actin and collagen-I. Thus, this system can be used as a model to study liver fibrosis by using different fibrogenic mediators in vitro.Keywords: electrospinning, collagen-I and fibronectin, surface modification of fiber, LX-2 cells, liver fibrosis
Procedia PDF Downloads 126158 Impact of Simulated Brain Interstitial Fluid Flow on the Chemokine CXC-Chemokine-Ligand-12 Release From an Alginate-Based Hydrogel
Authors: Wiam El Kheir, Anais Dumais, Maude Beaudoin, Bernard Marcos, Nick Virgilio, Benoit Paquette, Nathalie Faucheux, Marc-Antoine Lauzon
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The high infiltrative pattern of glioblastoma multiforme cells (GBM) is the main cause responsible for the actual standard treatments failure. The tumor high heterogeneity, the interstitial fluid flow (IFF) and chemokines guides GBM cells migration in the brain parenchyma resulting in tumor recurrence. Drug delivery systems emerged as an alternative approach to develop effective treatments for the disease. Some recent studies have proposed to harness the effect CXC-lchemokine-ligand-12 to direct and control the cancer cell migration through delivery system. However, the dynamics of the brain environment on the delivery system remains poorly understood. Nanoparticles (NPs) and hydrogels are known as good carriers for the encapsulation of different agents and control their release. We studied the release of CXCL12 (free or loaded into NPs) from an alginate-based hydrogel under static and indirect perfusion (IP) conditions. Under static conditions, the main phenomena driving CXCL12 release from the hydrogel was diffusion with the presence of strong interactions between the positively charged CXCL12 and the negatively charge alginate. CXCL12 release profiles were independent from the initial mass loadings. Afterwards, we demonstrated that the release could tuned by loading CXCL12 into Alginate/Chitosan-Nanoparticles (Alg/Chit-NPs) and embedded them into alginate-hydrogel. The initial burst release was substantially attenuated and the overall cumulative release percentages of 21%, 16% and 7% were observed for initial mass loadings of 0.07, 0.13 and 0.26 µg, respectively, suggesting stronger electrostatic interactions. Results were mathematically modeled based on Fick’s second law of diffusion framework developed previously to estimate the effective diffusion coefficient (Deff) and the mass transfer coefficient. Embedding the CXCL12 into NPs decreased the Deff an order of magnitude, which was coherent with experimental data. Thereafter, we developed an in-vitro 3D model that takes into consideration the convective contribution of the brain IFF to study CXCL12 release in an in-vitro microenvironment that mimics as faithfully as possible the human brain. From is unique design, the model also allowed us to understand the effect of IP on CXCL12 release in respect to time and space. Four flow rates (0.5, 3, 6.5 and 10 µL/min) which may increase CXCL12 release in-vivo depending on the tumor location were assessed. Under IP, cumulative percentages varying between 4.5-7.3%, 23-58.5%, 77.8-92.5% and 89.2-95.9% were released for the three initial mass loadings of 0.08, 0.16 and 0.33 µg, respectively. As the flow rate increase, IP culture conditions resulted in a higher release of CXCL12 compared to static conditions as the convection contribution became the main driving mass transport phenomena. Further, depending on the flow rate, IP had a direct impact on CXCL12 distribution within the simulated brain tissue, which illustrates the importance of developing such 3D in-vitro models to assess the efficiency of a delivery system targeting the brain. In future work, using this very model, we aim to understand the impact of the different phenomenon occurring on GBM cell behaviors in response to the resulting chemokine gradient subjected to various flow while allowing them to express their invasive characteristics in an in-vitro microenvironment that mimics the in-vivo brain parenchyma.Keywords: 3D culture system, chemokines gradient, glioblastoma multiforme, kinetic release, mathematical modeling
Procedia PDF Downloads 84157 Nanotechnology as a Futuristic Approach to Architecture with Special Reference to Chandigarh
Authors: Chaudhary Archana, Dhingra Poshika
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The architecture of the world is at a crossroads with the advent of new technology. The issues of energy efficiency and global warming are getting important with the coming times. New technologies are making their mark. For the architecture profession, nanotechnology will greatly impact construction materials and their properties. Nanotechnology, the understanding and control of matter at a scale of one to one hundred billions of a meter, is bringing incredible changes to the materials and processes of buildings. Materials will behave in many different ways as we are able to more precisely control their properties at the nanoscale. It is precisely called the next industrial revolution. We live in an age where scientific progress continues to transform human lifestyle. This is evermore true when it comes to the progress being made in the field of nanotechnology. This science stands to change and advance the practice of design in a multitude of ways – where architectural progress is being made at the molecular level. The nanotechnology has already been adopted in various buildings across the world. What an impact it shall have on the futuristic architecture in Chandigarh, India shall be discussed in the paper. But before we hurtle off toward a nano-utopia, we need to step back and ask ourselves whether this is a direction in which we really want to go.Keywords: building materials, energy efficiency, nanotechnology, sustainability
Procedia PDF Downloads 459156 Modified Surface Morphology, Structure and Enhanced Weathering Performance of Polyester-Urethane/Organoclay Nanocomposite Coatings
Authors: Gaurav Verma
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Organoclay loaded (0-5 weight %) polyester-urethane (PU) coatings were prepared with a branched hydroxyl-bearing polyester and an aliphatic poly-isocyanate. TEM micrographs show partial exfoliation and intercalation of clay platelets in organoclay-polyester dispersions. AFM surface images reveals that the PU hard domains tend to regularise and also self-organise into spherical shapes of sizes 50 nm (0 wt %), 60 nm (2 wt %) and 190 nm (4 wt %) respectively. IR analysis shows that PU chains have increasing tendency to interact with exfoliated clay platelets through hydrogen bonding. This interaction strengthens inter-chain linkages in PU matrix and hence improves anti-ageing properties. 1000 hours of accelerated weathering was evaluated by ATR spectroscopy, while yellowing and overall discoloration was quantified by the Δb* and ΔE* values of the CIELab colour scale. Post-weathering surface properties also showed improvement as the loss of thickness and reduction in gloss in neat PU was 25% and 42%; while it was just 3.5% and 14% respectively for the 2 wt% nanocomposite coating. This work highlights the importance of modifying surface and bulk properties of PU coatings at nanoscale, which led to improved performance in accelerated weathering conditions.Keywords: coatings, AFM, ageing, spectroscopy
Procedia PDF Downloads 454155 Nanoscale Photo-Orientation of Azo-Dyes in Glassy Environments Using Polarized Optical Near-Field
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
Procedia PDF Downloads 177154 PD-L1 Expression in Papillary Thyroid Carcinoma Arising Denovo or on Top of Autoimmune Thyroiditis
Authors: Dalia M. Abouelfadl, Noha N. Yassen, Marwa E. Shabana
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Background: The evolution of immune therapy motivated many to study the relation between immune response and progression of cancer. Little is known about expression of PD-L1 (a newly evolving immunotherapeutic drug) in papillary thyroid carcinoma (PTC) arising de-novo and PTC arising on top of autoimmune thyroiditis (Hashimoto's (HT) and lymphocytic thyroiditis (LT)). The aim of this work is to study the alteration of expression of PD-L1 in PTCs arising from de-novo or on top of HT OR LT using immunohistochemistry and image analyser system. Method: 100 paraffin blocks for PTC cases were collected retrospectively for staining using PD-L1 rabbit monoclonal antibody (BIOCARE-ACI 3171 A, C). The antibody expression is measured digitally using Image Analyzer Leica Qwin 3000, and the membranous and cytoplasmic expression of PD-L1 in tumor cells was considered positive. The results were correlated with tumor grade, size, and LN status. Results: The study samples consisted of 41 cases of PTC arising De novo, 36 cases on top of HT, and 23 on top of LT. Expression of PD-L1 was highest among the PTC-HL group (25 case-69%) followed by PTC-TL group (14 case-60.8%) then de-novo PTC (19 case-46%) with P Value < 0.05. PD-L1 expression correlated with nodal metastasis and was not relevant to tumor size or grade. Conclusion: The severity of the immune response in tumor microenvironment directly influences PTC prognosis. The anti PD-L1 Ab can be a very successful therapeutic agent for PTC arising on top of HT.Keywords: carcinoma, Hashimoto's, lymphocytic, papillary, PD-L1, thyroiditis
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