Search results for: magnetoelastically induced perpendicular magnetic anisotropy

Authors: Alex B. Cusick

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The objective of this study is to improve upon the current ²³⁸PuO₂ fuel technology for space and defense applications. Modern RTGs (radioisotope thermoelectric generators) utilize the heat generated from the radioactive decay of ²³⁸Pu to create heat and electricity for long term and remote missions. Application of RTG technology is limited by the scarcity and expense of producing the isotope, as well as the power output which is limited to only a few hundred watts. The scarcity and expense make the efficient use of ²³⁸Pu absolutely necessary. By utilizing the decay of ²³⁸Pu, not only to produce heat directly but to also indirectly induce fission in ²³⁹Pu (which is already present within currently used fuel), it is possible to see large increases in temperature which allows for a more efficient conversion to electricity and a higher power-to-weight ratio. This concept can reduce the quantity of ²³⁸Pu necessary for these missions, potentially saving millions on investment, while yielding higher power output. Current work investigating radioisotope power systems have focused on improving efficiency of the thermoelectric components and replacing systems which produce heat by virtue of natural decay with fission reactors. The technical feasibility of utilizing (α,n) reactions to induce fission within current radioisotopic fuels has not been investigated in any appreciable detail, and our study aims to thoroughly investigate the performance of many such designs, develop those with highest capabilities, and facilitate experimental testing of these designs. In order to determine the specific design parameters that maximize power output and the efficient use of ²³⁸Pu for future RTG units, MCNP6 simulations have been used to characterize the effects of modifying fuel composition, geometry, and porosity, as well as introducing neutron moderating, reflecting, and shielding materials to the system. Although this project is currently in the preliminary stages, the final deliverables will include sophisticated designs and simulation models that define all characteristics of multiple novel RTG fuels, detailed enough to allow immediate fabrication and testing. Preliminary work has consisted of developing a benchmark model to accurately represent the ²³⁸PuO₂ pellets currently in use by NASA; this model utilizes the alpha transport capabilities of MCNP6 and agrees well with experimental data. In addition, several models have been developed by varying specific parameters to investigate their effect on (α,n) and (n,fi ssion) reaction rates. Current practices in fuel processing are to exchange out the small portion of naturally occurring ¹⁸O and ¹⁷O to limit (α,n) reactions and avoid unnecessary neutron production. However, we have shown that enriching the oxide in ¹⁸O introduces a sufficient (α,n) reaction rate to support significant fission rates. For example, subcritical fission rates above 10⁸ f/cm³-s are easily achievable in cylindrical ²³⁸PuO₂ fuel pellets with a ¹⁸O enrichment of 100%, given an increase in size and a ⁹Be clad. Many viable designs exist and our intent is to discuss current results and future endeavors on this project.

Keywords: radioisotope thermoelectric generators (RTG), Pu-238, subcritical reactors, (alpha, n) reactions

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Authors: Inna Kornienko, Svetlana Guryeva, Anatoly Shekhter, Elena Petersen

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Transplantation is an effective treatment option for patients suffering from different end-stage diseases. However, it is plagued by a constant shortage of donor organs and the subsequent need of a lifelong immunosuppressive therapy for the patient. Currently some researchers look towards using of pig organs to replace human organs for transplantation since the matrix derived from porcine organs is a convenient substitute for the human matrix. As an initial step to create a new ex vivo tissue engineered model, optimized protocols have been created to obtain organ-specific acellular matrices and evaluated their potential as tissue engineered scaffolds for culture of normal cells and tumor cell lines. These protocols include decellularization by perfusion in a bioreactor system and immersion-agitation on an orbital shaker with use of various detergents (SDS, Triton X-100) and freezing. Complete decellularization – in terms of residual DNA amount – is an important predictor of probability of immune rejection of materials of natural origin. However, the signs of cellular material may still remain within the matrix even after harsh decellularization protocols. In this regard, the matrices obtained from tissues of low-immunogenic pigs with α3Galactosyl-tranferase gene knock out (GalT-KO) may be a promising alternative to native animal sources. The research included a study of induced effect of frozen and fresh fragments of GalT-KO skin on healing of full-thickness plane wounds in 80 rats. Commercially available wound dressings (Ksenoderm, Hyamatrix and Alloderm) as well as allogenic skin were used as a positive control and untreated wounds were analyzed as a negative control. The results were evaluated on the 4th day after grafting, which corresponds to the time of start of normal wound epithelization. It has been shown that a non-specific immune response in models treated with GalT-Ko pig skin was milder than in all the control groups. Research has been performed to measure technical skin characteristics: stiffness and elasticity properties, corneometry, tevametry, and cutometry. These metrics enabled the evaluation of hydratation level, corneous layer husking level, as well as skin elasticity and micro- and macro-landscape. These preliminary data may contribute to development of personalized transplantable organs from GalT-Ko pigs with significantly limited potential of immune rejection. By applying growth factors to a decellularized skin sample it is possible to achieve various regenerative effects based on the particular situation. In this particular research BMP2 and Heparin-binding EGF-like growth factor have been used. Ideally, a bioengineered organ must be biocompatible, non-immunogenic and support cell growth. Porcine organs are attractive for xenotransplantation if severe immunologic concerns can be bypassed. The results indicate that genetically modified pig tissues with knock-outed α3Galactosyl-tranferase gene may be used for production of low-immunogenic matrix suitable for transplantation.

Keywords: decellularization, low-immunogenic, matrix, scaffolds, transplants

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Authors: Manta Nowbuth, Marie Anais Kimberley Therese

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The vulnerability of coastal areas to storm surges stands as a critical global concern. The increasing frequency and intensity of extreme weather events have increased the risks faced by communities living along the coastlines Worldwide. Small Island developing states (SIDS) stands out as being exceptionally vulnerable, coastal regions, ecosystems of human habitation and natural forces, bear witness to the frontlines of climate-induced challenges, and the intensification of storm surges underscores the urgent need for a comprehensive understanding of coastal vulnerability. With limited landmass, low-lying terrains, and resilience on coastal resources, SIDS face an amplified vulnerability to the consequences of storm surges, the delicate balance between human activities and environmental dynamics in these island nations increases the urgency of tailored strategies for assessing and mitigating coastal vulnerability. This research uses an approach to evaluate the vulnerability of coastal communities in Mauritius. The Satellite imagery analysis makes use of sentinel satellite imageries, modified normalised difference water index, classification techniques and the DSAS add on to quantify the extent of shoreline erosion or accumulation, providing a spatial perspective on coastal vulnerability. The coastal Vulnerability Index (CVI) is applied by Gonitz et al Formula, this index considers factors such as coastal slope, sea level rise, mean significant wave height, and tidal range. Weighted assessments identify regions with varying levels of vulnerability, ranging from low to high. The study was carried out in a Village Located in the south of Mauritius, namely Rivière des Galets, with a population of about 500 people over an area of 60,000m². The Village of Rivière des Galets being located in the south, and the southern coast of Mauritius being exposed to the open Indian ocean, is vulnerable to swells, The swells generated by the South east trade winds can lead to large waves and rough sea conditions along the Southern Coastline which has an impact on the coastal activities, including fishing, tourism and coastal Infrastructures, hence, On the one hand, the results highlighted that from a stretch of 123km of coastline the linear rate regression for the 5 –year span varies from-24.1m/yr. to 8.2m/yr., the maximum rate of change in terms of eroded land is -24m/yr. and the maximum rate of accretion is 8.2m/yr. On the other hand, the coastal vulnerability index varies from 9.1 to 45.6 and it was categorised into low, moderate, high and very high risks zones. It has been observed that region which lacks protective barriers and are made of sandy beaches are categorised as high risks zone and hence it is imperative to high risk regions for immediate attention and intervention, as they will most likely be exposed to coastal hazards and impacts from climate change, which demands proactive measures for enhanced resilience and sustainable adaptation strategies.

Keywords: climate change, coastal vulnerability, disaster management, remote sensing, satellite imagery, storm surge

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Authors: S. N. T. I. Sampath, J. M. S. Jayasinghe, A. P. Attanayake, V. Karunaratne

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Diabetes mellitus is one of the major public health posers throughout the world today that incidence and associated with increasing mortality. Insufficient regulation of the blood glucose level might be serious effects for health and its necessity to identify new therapeutics that have ability to reduce hyperglycaemic condition in the human body. Even though synthetic antidiabetic drugs are more effective to control diabetes mellitus, there are considerable side effects have been reported. Thus, there is an increasing demand for searching new natural products having high antidiabetic activity with lesser side effects. The purposes of the present study were to evaluate different physical parameters and in-vitro and in-vivo antidiabetic potential of the selected combined medicinal plant extracts mixture composed of leaves of Murraya koenigii, cloves of Allium sativum, fruits of Garcinia queasita and seeds of Piper nigrum. The selected plants parts were mixed and ground together and extracted sequentially into the hexane, ethyl acetate and methanol. Solvents were evaporated and they were further dried by freeze-drying to obtain a fine powder of each extract. Various physical parameters such as moisture, total ash, acid insoluble ash and water soluble ash were evaluated using standard test procedures. In-vitro antidiabetic activity of combined plant extracts mixture was screened using enzyme assays such as α-amylase inhibition assay and α-glucosidase inhibition assay. The acute anti-hyperglycaemic activity was performed using oral glucose tolerance test for the streptozotocin induced diabetic Wistar rats to find out in-vivo antidiabetic activity of combined plant extracts mixture and it was assessed through total oral glucose tolerance curve (TAUC) values. The percentage of moisture content, total ash content, acid insoluble ash content and water soluble ash content were ranged of 7.6-17.8, 8.1-11.78, 0.019-0.134 and 6.2-9.2 respectively for the plant extracts and those values were less than standard values except the methanol extract. The hexane and ethyl acetate extracts exhibited highest α-amylase (IC50 = 25.7 ±0.6; 27.1 ±1.2 ppm) and α-glucosidase (IC50 = 22.4 ±0.1; 33.7 ±0.2 ppm) inhibitory activities than methanol extract (IC50 = 360.2 ±0.6; 179.6 ±0.9 ppm) when compared with the acarbose positive control (IC50 = 5.7 ±0.4; 17.1 ±0.6 ppm). The TAUC values for hexane, ethyl acetate, and methanol extracts and glibenclamide (positive control) treated rats were 8.01 ±0.66; 8.05 ±1.07; 8.40±0.50; 5.87 ±0.93 mmol/L.h respectively, whereas in diabetic control rats the TAUC value was 13.22 ±1.07 mmol/L.h. Administration of plant extracts treated rats significantly suppressed (p<0.05) the rise in plasma blood glucose levels compared to control rats but less significant than glibenclamide. The obtained results from in-vivo and in-vitro antidiabetic study showed that the hexane and ethyl acetate extracts of selected combined plant mixture might be considered as a potential source to isolate natural antidiabetic agents and physical parameters of hexane and ethyl acetate extracts will helpful to develop antidiabetic drug with further standardize properties.

Keywords: diabetes mellitus, in-vitro antidiabetic assays, medicinal plants, standardization

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Authors: Dario Milani, Guido Morgenthal

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Fluid dynamic computation of wind caused forces on bluff bodies e.g light flexible civil structures or high incidence of ground approaching airplane wings, is one of the major criteria governing their design. For such structures a significant dynamic response may result, requiring the usage of small scale devices as guide-vanes in bridge design to control these effects. The focus of this paper is on the numerical simulation of the bluff body problem involving multiscale phenomena induced by small scale devices. One of the solution methods for the CFD simulation that is relatively successful in this class of applications is the Vortex Particle Method (VPM). The method is based on a grid free Lagrangian formulation of the Navier-Stokes equations, where the velocity field is modeled by particles representing local vorticity. These vortices are being convected due to the free stream velocity as well as diffused. This representation yields the main advantages of low numerical diffusion, compact discretization as the vorticity is strongly localized, implicitly accounting for the free-space boundary conditions typical for this class of FSI problems, and a natural representation of the vortex creation process inherent in bluff body flows. When the particle resolution reaches the Kolmogorov dissipation length, the method becomes a Direct Numerical Simulation (DNS). However, it is crucial to note that any solution method aims at balancing the computational cost against the accuracy achievable. In the classical VPM method, if the fluid domain is discretized by Np particles, the computational cost is O(Np2). For the coupled FSI problem of interest, for example large structures such as long-span bridges, the aerodynamic behavior may be influenced or even dominated by small structural details such as barriers, handrails or fairings. For such geometrically complex and dimensionally large structures, resolving the complete domain with the conventional VPM particle discretization might become prohibitively expensive to compute even for moderate numbers of particles. It is possible to reduce this cost either by reducing the number of particles or by controlling its local distribution. It is also possible to increase the accuracy of the solution without increasing substantially the global computational cost by computing a correction of the particle-particle interaction in some regions of interest. In this paper different strategies are presented in order to extend the conventional VPM method to reduce the computational cost whilst resolving the required details of the flow. The methods include temporal sub stepping to increase the accuracy of the particles convection in certain regions as well as dynamically re-discretizing the particle map to locally control the global and the local amount of particles. Finally, these methods will be applied on a test case and the improvements in the efficiency as well as the accuracy of the proposed extension to the method are presented. The important benefits in terms of accuracy and computational cost of the combination of these methods will be thus presented as long as their relevant applications.

Keywords: adaptation, fluid dynamic, remeshing, substepping, vortex particle method

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Authors: Aleksandra Bylinska, Samantha Slight-Webb, Kevin Thomas, Miles Smith, Susan Macwana, Nicolas Dominguez, Eliza Chakravarty, Joan T. Merrill, Judith A. James, Joel M. Guthridge

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Background: Systemic Lupus Erythematosus (SLE) is an interferon-related autoimmune disease characterized by B cell dysfunction. One of the main hallmarks is a loss of tolerance to self-antigens leading to increased levels of autoantibodies against nuclear components (ANAs). However, up to 20% of healthy ANA+ individuals will not develop clinical illness. SLE is more prevalent among women and minority populations (African, Asian American and Hispanics). Moreover, African Americans have a stronger interferon (IFN) signature and develop more severe symptoms. The exact mechanisms involved in ethnicity-dependent B cell dysregulation and the progression of autoimmune disease from ANA+ healthy individuals to clinical disease remains unclear. Methods: Peripheral blood mononuclear cells (PBMCs) from African (AA) and European American (EA) ANA- (n=12), ANA+ (n=12) and SLE (n=12) individuals were assessed by multimodal scRNA-Seq/CITE-Seq methods to examine differential gene signatures in specific B cell subsets. Library preparation was done with a 10X Genomics Chromium according to established protocols and sequenced on Illumina NextSeq. The data were further analyzed for distinct cluster identification and differential gene signatures in the Seurat package in R and pathways analysis was performed using Ingenuity Pathways Analysis (IPA). Results: Comparing all subjects, 14 distinct B cell clusters were identified using a community detection algorithm and visualized with Uniform Manifold Approximation Projection (UMAP). The proportion of each of those clusters varied by disease status and ethnicity. Transitional B cells trended higher in ANA+ healthy individuals, especially in AA. Ribonucleoprotein high population (HNRNPH1 elevated, heterogeneous nuclear ribonucleoprotein, RNP-Hi) of proliferating Naïve B cells were more prevalent in SLE patients, specifically in EA. Interferon-induced protein high population (IFIT-Hi) of Naive B cells are increased in EA ANA- individuals. The proportion of memory B cells and plasma cells clusters tend to be expanded in SLE patients. As anticipated, we observed a higher signature of cytokine-related pathways, especially interferon, in SLE individuals. Pathway analysis among AA individuals revealed an NRF2-mediated Oxidative Stress response signature in the transitional B cell cluster, not seen in EA individuals. TNFR1/2 and Sirtuin Signaling pathway genes were higher in AA IFIT-Hi Naive B cells, whereas they were not detected in EA individuals. Interferon signaling was observed in B cells in both ethnicities. Oxidative phosphorylation was found in age-related B cells (ABCs) for both ethnicities, whereas Death Receptor Signaling was found only in EA patients in these cells. Interferon-related transcription factors were elevated in ABCs and IFIT-Hi Naive B cells in SLE subjects of both ethnicities. Conclusions: ANA+ healthy individuals have altered gene expression pathways in B cells that might drive apoptosis and subsequent clinical autoimmune pathogenesis. Increases in certain regulatory pathways may delay progression to SLE. Further, AA individuals have more elevated activation pathways that may make them more susceptible to SLE.

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Procedia PDF Downloads 175

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

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Authors: D. Heinemann, S. Schramm, S. Knabner, D. Baumgarten

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Purpose: Applying solder paste to printed circuit boards (PCB) with stencils has been the method of choice over the past years. A new method uses a jet printer to deposit tiny droplets of solder paste through an ejector mechanism onto the board. This allows for more flexible PCB layouts with smaller components. Due to the viscosity of the solder paste, air blisters can be trapped in the cartridge. This can lead to missing solder joints or deviations in the applied solder volume. Therefore, a built-in and real-time inspection of the printing process is needed to minimize uncertainties and increase the efficiency of the process by immediate correction. The objective of the current study is the design of an optimal imaging system and the development of an automatic algorithm for the detection of applied solder joints from optical from the captured images. Methods: In a first approach, a camera module connected to a microcomputer and LED strips are employed to capture images of the printed circuit board under four different illuminations (white, red, green and blue). Subsequently, an improved system including a ring light, an objective lens, and a monochromatic camera was set up to acquire higher quality images. The obtained images can be divided into three main components: the PCB itself (i.e., the background), the reflections induced by unsoldered positions or screw holes and the solder joints. Non-uniform illumination is corrected by estimating the background using a morphological opening and subtraction from the input image. Image sharpening is applied in order to prevent error pixels in the subsequent segmentation. The intensity thresholds which divide the main components are obtained from the multimodal histogram using three probability density functions. Determining the intersections delivers proper thresholds for the segmentation. Remaining edge gradients produces small error areas which are removed by another morphological opening. For quantitative analysis of the segmentation results, the dice coefficient is used. Results: The obtained PCB images show a significant gradient in all RGB channels, resulting from ambient light. Using different lightings and color channels 12 images of a single PCB are available. A visual inspection and the investigation of 27 specific points show the best differentiation between those points using a red lighting and a green color channel. Estimating two thresholds from analyzing the multimodal histogram of the corrected images and using them for segmentation precisely extracts the solder joints. The comparison of the results to manually segmented images yield high sensitivity and specificity values. Analyzing the overall result delivers a Dice coefficient of 0.89 which varies for single object segmentations between 0.96 for a good segmented solder joints and 0.25 for single negative outliers. Conclusion: Our results demonstrate that the presented optical imaging system and the developed algorithm can robustly detect solder joints on printed circuit boards. Future work will comprise a modified lighting system which allows for more precise segmentation results using structure analysis.

Keywords: printed circuit board jet-printing, inspection, segmentation, solder paste detection

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Authors: Ayoti Banerjee, Meenakshi Banerjee

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The study of metamorphic reaction textures is important in contributing to our understanding of the evolution of metamorphic terranes. Where preserved, they provide information on changes in the P-T conditions during the metamorphic history of the rock, and thus allow us to speculate on the P-T-t evolution of the terrane. Mafic dykes have attracted the attention of petrologists because they act as window to mantle. This rock represents a mafic dyke of doleritic composition. It is fine to medium grained in which clinopyroxene are enclosed by the lath shaped plagioclase grains to form spectacular ophitic texture. At places, sub ophitic texture was also observed. Grains of pyroxene and plagioclase show very less deformation typically plagioclase showing deformed lamella along with plagioclase-clinopyroxene-phyric granoblastic fabric within a groundmass of feldspar microphenocrysts and Fe–Ti oxides. Both normal and reverse zoning were noted in the plagioclase laths. The clinopyroxene grains contain exsolved phases such as orthopyroxene, plagioclase, magnetite, ilmenite along the cleavage traces and the orthopyroxene lamella form granules in the periphery of the clinopyroxene grains. Garnet corona also develops preferentially around plagioclase at the contact of clinopyroxene, ilmenite or magnetite. Tiny quartz and K-fs grains showed symplectic intergrowth with garnet at a few places. The product quartz formed along with garnet rims the coronal garnet and the reacting clinopyroxene. Thin amphibole corona formed along the periphery of deformed plagioclase and clinopyroxene occur as patches over the magmatic minerals. The amphibole coronas cannot be assigned to a late magmatic stage and are interpreted as reactive being restricted to the contact between clinopyroxene and plagioclase, thus postdating the crystallization of both. The amphibole and garnet do not share grain boundary in the entire rock and is thus pointing towards simultaneous crystallization. Olivine is absent. Spectacular myrmekitic growth of orthoclase and quartz rimming the plagioclase is consistent with the potash metasomatic effects that is also found in other rocks of this region. These textural features are consistent with a phase of fluid induced metamorphism (retrogression). But the appearance of coronal garnet and amphibole exclusive of each other reflects the participation if Ti as the prime reason. Presence of Ti as a reactant phase is a must for amphibole forming reactions whereas it is not so in case of garnet forming reactions although the reactants are the same plagioclase and clinopyroxene in both cases. These findings are well validated by petrographical and textural analysis. In order to obtain balanced chemical reactions that explain formation of amphibole and garnet in the mafic dyke rocks a matrix operation technique called Singular Value Decomposition (SVD) was adopted utilizing the measured chemical compositions of the minerals. The computer program C-Space was used for this purpose and the required compositional matrix. Data fed to C-Space was after doing cation-calculation of the oxide percentages obtained from EPMA analysis. The Garnet-Clinopyroxene geothermometer yielded a temperature of 650 degrees Celsius. The Garnet-Clinopyroxene-Plagioclase geobarometer and Al-in amphibole yielded roughly 7.5 kbar pressure.

Keywords: corona, dolerite, geothermometer, metasomatism, metamorphic reaction texture, retrogression

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Authors: Bijit Kalita, K. V. N. Surendra

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The pulley works under both compressive loading due to contacting belt in tension and central torque due to cause rotation. In a power transmission system, the belt pulley assemblies offer a contact problem in the form of two mating cylindrical parts. In this work, we modeled a pulley as a heavy two-dimensional circular disk. Stress analysis due to contact loading in the pulley mechanism is performed. Finite element analysis (FEA) is conducted for a pulley to investigate the stresses experienced on its inner and outer periphery. In most of the heavy-duty applications, most frequently used mechanisms to transmit power in applications such as automotive engines, industrial machines, etc. is Belt Drive. Usually, very heavy circular disks are used as pulleys. A pulley could be entitled as a drum and may have a groove between two flanges around the circumference. A rope, belt, cable or chain can be the driving element of a pulley system that runs over the pulley inside the groove. A pulley is experienced by normal and shear tractions on its contact region in the process of motion transmission. The region may be belt-pulley contact surface or pulley-shaft contact surface. In 1895, Hertz solved the elastic contact problem for point contact and line contact of an ideal smooth object. Afterward, this hypothesis is generally utilized for computing the actual contact zone. Detailed stress analysis in such contact region of such pulleys is quite necessary to prevent early failure. In this paper, the results of the finite element analyses carried out on the compressed disk of a belt pulley arrangement using fracture mechanics concepts are shown. Based on the literature on contact stress problem induced in the wide field of applications, generated stress distribution on the shaft-pulley and belt-pulley interfaces due to the application of high-tension and torque was evaluated in this study using FEA concepts. Finally, the results obtained from ANSYS (APDL) were compared with the Hertzian contact theory. The study is mainly focused on the fatigue life estimation of a rotating part as a component of an engine assembly using the most famous Paris equation. Digital Image Correlation (DIC) analyses have been performed using the open-source software. From the displacement computed using the images acquired at a minimum and maximum force, displacement field amplitude is computed. From these fields, the crack path is defined and stress intensity factors and crack tip position are extracted. A non-linear least-squares projection is used for the purpose of the estimation of fatigue crack growth. Further study will be extended for the various application of rotating machinery such as rotating flywheel disk, jet engine, compressor disk, roller disk cutter etc., where Stress Intensity Factor (SIF) calculation plays a significant role on the accuracy and reliability of a safe design. Additionally, this study will be progressed to predict crack propagation in the pulley using maximum tangential stress (MTS) criteria for mixed mode fracture.

Keywords: crack-tip deformations, contact stress, stress concentration, stress intensity factor

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Authors: Aberdam Edith, Sangari Linda, Petit Isabelle, Aberdam Daniel

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Background and Rationale: Transparent avascularised cornea is essential for normal vision and depends on limbal stem cells (LSC) that reside between the cornea and the conjunctiva. Ocular burns or injuries may destroy the limbus, causing limbal stem cell deficiency (LSCD). The cornea becomes vascularised by invaded conjunctival cells, the stroma is scarring, resulting in corneal opacity and loss of vision. Grafted autologous limbus or cultivated autologous LCS can restore the vision, unless the two eyes are affected. Alternative cellular sources have been tested in the last decades, including oral mucosa or hair follicle epithelial cells. However, only partial success has been achieved by the use of these cells since they were not able to uniformly commit into corneal epithelial cells. Human pluripotent stem cells (iPSC) display both unlimited growth capacity and ability to differentiate into any cell type. Our goal was to design a standardized and reproducible protocol to produce transplantable autologous LSC from patients through cell reprogramming technology. Methodology: First, keratinocyte primary culture was established from a small number of plucked hair follicles of healthy donors. The resulting epithelial cells were reprogrammed into induced pluripotent stem cells (iPSCs) and further differentiate into corneal epithelial cells (CEC), according to a robust protocol that recapitulates the main step of corneal embryonic development. qRT-PCR analysis and immunofluorescent staining during the course of differentiation confirm the expression of stage specific markers of corneal embryonic lineage. First appear ectodermal progenitor-specific cytokeratins K8/K18, followed at day 7 by limbal-specific PAX6, TP63 and cytokeratins K5/K14. At day 15, K3/K12+-corneal cells are present. To amplify the iPSC-derived LSC (named COiPSC), intact small epithelial colonies were detached and cultivated in limbal cell-specific medium. In that culture conditions, the COiPSC can be frozen and thaw at any passage, while retaining their corneal characteristics for at least eight passages. To evaluate the potential of COiPSC as an alternative ocular toxicity model, COiPSC were treated at passage P0 to P4 with increasing amounts of SDS and Benzalkonium. Cell proliferation and apoptosis of treated cells was compared to LSC and the SV40-immortalized human corneal epithelial cell line (HCE) routinely used by cosmetological industrials. Of note, HCE are more resistant to toxicity than LSC. At P0, COiPSC were systematically more resistant to chemical toxicity than LSC and even to HCE. Remarkably, this behavior changed with passage since COiPSC at P2 became identical to LSC and thus closer to physiology than HCE. Comparative transcriptome analysis confirmed that COiPSC from P2 are similar to a mixture of LSC and CEC. Finally, by organotypic reconstitution assay, we demonstrated the ability of COiPSC to produce a 3D corneal epithelium on a stromal equivalent made of keratocytes. Conclusion: COiPSC could become valuable for two main applications: (1) an alternative robust tool to perform, in a reproducible and physiological manner, toxicity assays for cosmetic products and pharmacological tests of drugs. (2). COiPSC could become an alternative autologous source for cornea transplantation for LSCD.

Keywords: Limbal stem cell deficiency, iPSC, cornea, limbal stem cells

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

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

Keywords: sonodynamic therapy, nanoparticles, tumour ablation, ultrasound

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Authors: Chethana V. Casiker, Jagadishakumara B., Sunil G. M., Chaithra K., M. Soubadra Devy

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A majority of the world’s food crops depends on insects for pollination, among which bees are the most dominant taxon. Bees pollinate vegetables, fruits and oilseeds which are rich in essential micronutrients. Besides being a prerequisite for a nutritionally secure diet, agrarian economies such as India depend heavily on pollination for good yield and quality of the product. As cities all over the world expand rapidly, large tracts of green spaces are being built up. This, along with high usage of agricultural chemicals has reduced floral diversity and shrunk bee habitats. Indeed, pollinator decline is being reported from various parts of the world. Further, the FAO has reported a huge increase in the area of land under cultivation of pollinator-dependent crops. In the light of increasing demand for pollination and disappearing natural habitats, it is critical to understand whether and how urban spaces can support pollinators. To this end, this study investigates the influence of landscape and local habitat quality on bee community dynamics. To capture the dynamics of expanding cityscapes, the study employs a space for time substitution, wherein a transect along the gradient of urbanization substitutes a timeframe of increasing urbanization. This will help understand how pollinators would respond to changes induced by increasing intensity of urbanization in the future. Bengaluru, one of the fastest growing cities of Southern India, is an excellent site to study impacts associated with urbanization. With sites moving away from the Bengaluru’s centre and towards its peripheries, this study captures the changes in bee species diversity and richness along a gradient of urbanization. Bees were sampled under different land use types as well as in different types of vegetation, including plantations, croplands, fallow land, parks, lake embankments, and private gardens. The relationship between bee community metrics and key drivers such as a percentage of built-up area, land use practices, and floral resources was examined. Additionally, data collected using questionnaire interviews were used to understand people’s perceptions towards and level of dependence on pollinators. Our results showed that urban areas are capable of supporting bees. In fact, a greater diversity of bees was recorded in urban sites compared to adjoining rural areas. This suggests that bees are able to seek out patchy resources and survive in small fragments of habitat. Bee abundance and species richness correlated positively with floral abundance and richness, indicating the role of vegetation in providing forage and nesting sites which are crucial to their survival. Bee numbers were seen to decrease with increase in built-up area demonstrating that impervious surfaces could act as deterrents. Findings from this study challenge the popular notion of cities being biodiversity-bare spaces. There is indeed scope for conserving bees in urban landscapes, provided that there are city-scale planning and local initiative. Bee conservation can go hand in hand with efforts such as urban gardening and terrace farming that could help cities urbanize sustainably.

Keywords: bee, landscape ecology, urbanization, urban pollination

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Authors: Maria Lazari, Lorenzo Sanavia

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Mechanics of unsaturated soils has been an active field of research in the last decades. Efficient constitutive models that take into account the partial saturation of soil are necessary to solve a number of engineering problems e.g. instability of slopes and cuts due to heavy rainfalls. A large number of constitutive models can now be found in the literature that considers fundamental issues associated with the unsaturated soil behaviour, like the volume change and shear strength behaviour with suction or saturation changes. Partially saturated soils may either expand or collapse upon wetting depending on the stress level, and it is also possible that a soil might experience a reversal in the volumetric behaviour during wetting. Shear strength of soils also changes dramatically with changes in the degree of saturation, and a related engineering problem is slope failures caused by rainfall. There are several states of the art reviews over the last years for studying the topic, usually providing a thorough discussion of the stress state, the advantages, and disadvantages of specific constitutive models as well as the latest developments in the area of unsaturated soil modelling. However, only a few studies focused on the coupling between partial saturation states and time effects on the behaviour of geomaterials. Rate dependency is experimentally observed in the mechanical response of granular materials, and a viscoplastic constitutive model is capable of reproducing creep and relaxation processes. Therefore, in this work an elasto-viscoplastic constitutive model for unsaturated soils is proposed and validated on the basis of experimental data. The model constitutes an extension of an existing elastoplastic strain-hardening constitutive model capable of capturing the behaviour of variably saturated soils, based on energy conjugated stress variables in the framework of superposed continua. The purpose was to develop a model able to deal with possible mechanical instabilities within a consistent energy framework. The model shares the same conceptual structure of the elastoplastic laws proposed to deal with bonded geomaterials subject to weathering or diagenesis and is capable of modelling several kinds of instabilities induced by the loss of hydraulic bonding contributions. The novelty of the proposed formulation is enhanced with the incorporation of density dependent stiffness and hardening coefficients in order to allow the modeling of the pycnotropy behaviour of granular materials with a single set of material constants. The model has been implemented in the commercial FE platform PLAXIS, widely used in Europe for advanced geotechnical design. The algorithmic strategies adopted for the stress-point algorithm had to be revised to take into account the different approach adopted by PLAXIS developers in the solution of the discrete non-linear equilibrium equations. An extensive comparison between models with a series of experimental data reported by different authors is presented to validate the model and illustrate the capability of the newly developed model. After the validation, the effectiveness of the viscoplastic model is displayed by numerical simulations of a partially saturated slope failure of the laboratory scale and the effect of viscosity and degree of saturation on slope’s stability is discussed.

Keywords: PLAXIS software, slope, unsaturated soils, Viscoplasticity

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Authors: Adenike Adesanya, Nonthaphat Wong, Xiang-Yun Lan, Shea Ping Yip, Chien-Ling Huang

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Background: The most challenging mutation of the oncokinase BCR-ABL protein T315I, which is commonly known as the “gatekeeper” mutation and is notorious for its strong resistance to almost all tyrosine kinase inhibitors (TKIs), especially imatinib. Therefore, this study aims to identify T315I-dependent downstream microRNA (miRNA) pathways associated with drug resistance in chronic myeloid leukemia (CML) for prognostic and therapeutic purposes. Methods: T315I-carrying K562 cell clones (K562-T315I) were generated by the CRISPR-Cas9 system. Imatinib-treated K562-T315I cells were subjected to small RNA library preparation and next-generation sequencing. Putative lncRNA-miRNA-mRNA networks were analyzed with (i) DESeq2 to extract differentially expressed miRNAs, using Padj value of 0.05 as cut-off, (ii) STarMir to obtain potential miRNA response element (MRE) binding sites of selected miRNAs on lncRNA H19, (iii) miRDB, miRTarbase, and TargetScan to predict mRNA targets of selected miRNAs, (iv) IntaRNA to obtain putative interactions between H19 and the predicted mRNAs, (v) Cytoscape to visualize putative networks, and (vi) several pathway analysis platforms – Enrichr, PANTHER and ShinyGO for pathway enrichment analysis. Moreover, mitochondria isolation and transcript quantification were adopted to determine the new mechanism involved in T315I-mediated resistance of CML treatment. Results: Verification of the CRISPR-mediated mutagenesis with digital droplet PCR detected the mutation abundance of ≥80%. Further validation showed the viability of ≥90% by cell viability assay, and intense phosphorylated CRKL protein band being detected with no observable change for BCR-ABL and c-ABL protein expressions by Western blot. As reported by several investigations into hematological malignancies, we determined a 7-fold increase of H19 expression in K562-T315I cells. After imatinib treatment, a 9-fold increment was observed. DESeq2 revealed 171 miRNAs were differentially expressed K562-T315I, 112 out of these miRNAs were identified to have MRE binding regions on H19, and 26 out of the 112 miRNAs were significantly downregulated. Adopting the seed-sequence analysis of these identified miRNAs, we obtained 167 mRNAs. 6 hub miRNAs (hsa-let-7b-5p, hsa-let-7e-5p, hsa-miR-125a-5p, hsa-miR-129-5p, and hsa-miR-372-3p) and 25 predicted genes were identified after constructing hub miRNA-target gene network. These targets demonstrated putative interactions with H19 lncRNA and were mostly enriched in pathways related to cell proliferation, senescence, gene silencing, and pluripotency of stem cells. Further experimental findings have also shown the up-regulation of mitochondrial transcript and lncRNA MALAT1 contributing to the lncRNA-miRNA-mRNA networks induced by BCR-ABL T315I mutation. Conclusions: Our results have indicated that lncRNA-miRNA regulators play a crucial role not only in leukemogenesis but also in drug resistance, considering the significant dysregulation and interactions in the K562-T315I cell model generated by CRISPR-Cas9. In silico analysis has further shown that lncRNAs H19 and MALAT1 bear several complementary miRNA sites. This implies that they could serve as a sponge, hence sequestering the activity of the target miRNAs.

Keywords: chronic myeloid leukemia, imatinib resistance, lncRNA-miRNA-mRNA, T315I mutation

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Authors: Erica Cochran Hameen, Bobuchi Ken-Opurum, Mounica Guturu

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The United Stated (U.S.) populous spends the majority of their time indoors in spaces where building codes and voluntary sustainability standards provide clear Indoor Environmental Quality (IEQ) metrics. The existing sustainable building standards and codes are aimed towards improving IEQ, health of occupants, and reducing the negative impacts of buildings on the environment. While they address the post-occupancy stage of buildings, there are fewer standards on the pre-occupancy stage thereby placing a large labor population in environments much less regulated. Construction personnel are often exposed to a variety of uncomfortable and unhealthy elements while on construction sites, primarily thermal, visual, acoustic, and air quality related. Construction site power generators, equipment, and machinery generate on average 9 decibels (dBA) above the U.S. OSHA regulations, creating uncomfortable noise levels. Research has shown that frequent exposure to high noise levels leads to chronic physiological issues and increases noise induced stress, yet beyond OSHA no other metric focuses directly on the impacts of noise on contractors’ well-being. Research has also associated natural light with higher productivity and attention span, and lower cases of fatigue in construction workers. However, daylight is not always available as construction workers often perform tasks in cramped spaces, dark areas, or at nighttime. In these instances, the use of artificial light is necessary, yet lighting standards for use during lengthy tasks and arduous activities is not specified. Additionally, ambient air, contaminants, and material off-gassing expelled at construction sites are one of the causes of serious health effects in construction workers. Coupled with extreme hot and cold temperatures for different climate zones, health and productivity can be seriously compromised. This research evaluates the impact of existing green building metrics on construction and risk management, by analyzing two codes and nine standards including LEED, WELL, and BREAM. These metrics were chosen based on the relevance to the U.S. construction industry. This research determined that less than 20% of the sustainability context within the standards and codes (texts) are related to the pre-occupancy building sector. The research also investigated the impact of construction personnel’s health and well-being on construction management through two surveys of project managers and on-site contractors’ perception of their work environment on productivity. To fully understand the risks of limited Environmental and Health Quality metrics for contractors (EHQ) this research evaluated the connection between EHQ factors such as inefficient lighting, on construction workers and investigated the correlation between various site coping strategies for comfort and productivity. Outcomes from this research are three-pronged. The first includes fostering a discussion about the existing conditions of EQH elements, i.e. thermal, lighting, ergonomic, acoustic, and air quality on the construction labor force. The second identifies gaps in sustainability standards and codes during the pre-occupancy stage of building construction from ground-breaking to substantial completion. The third identifies opportunities for improvements and mitigation strategies to improve EQH such as increased monitoring of effects on productivity and health of contractors and increased inclusion of the pre-occupancy stage in green building standards.

Keywords: construction contractors, health and well-being, environmental quality, risk management

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Authors: Daniel Puciato, Piotr Oleśniewicz, Julita Markiewicz-Patkowska, Krzysztof Widawski, Michał Rozpara, Władysław Mynarski, Agnieszka Gawlik, Małgorzata Dębska, Soňa Jandová

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Physical activity as a part of people’s everyday life reduces the risk of many diseases, including those induced by lifestyle, e.g. obesity, type 2 diabetes, osteoporosis, coronary heart disease, degenerative arthritis, and certain types of cancer. That refers particularly to professionally active people, including the early senior group working on non-manual positions. The aim of the study is to evaluate the relationship between physical activity and the socio-economic status of non-manual workers from Wroclaw—one of the biggest cities in Poland, a model setting for such investigations in this part of Europe. The crucial problem in the research is to find out the percentage of respondents who meet the health-related recommendations of the World Health Organization (WHO) concerning the volume, frequency, and intensity of physical activity, as well as to establish if the most important socio-economic factors, such as gender, age, education, marital status, per capita income, savings and debt, determine the compliance with the WHO physical activity recommendations. During the research, conducted in 2013, 1,170 people (611 women and 559 men) aged 21–60 years were examined. A diagnostic poll method was applied to collect the data. Physical activity was measured with the use of the short form of the International Physical Activity Questionnaire with extended socio-demographic questions, i.e. concerning gender, age, education, marital status, income, savings or debts. To evaluate the relationship between physical activity and selected socio-economic factors, logistic regression was used (odds ratio statistics). Statistical inference was conducted on the adopted ex ante probability level of p<0.05. The majority of respondents met the volume of physical effort recommended for health benefits. It was particularly noticeable in the case of the examined men. The probability of compliance with the WHO physical activity recommendations was highest for workers aged 21–30 years with secondary or higher education who were single, received highest incomes and had savings. The results indicate the relations between physical activity and socio-economic status in the examined women and men. People with lower socio-economic status (e.g. manual workers) are physically active primarily at work, whereas those better educated and wealthier implement physical effort primarily in their leisure time. Among the investigated subjects, the youngest group of non-manual workers have the best chances to meet the WHO standards of physical activity. The study also confirms that secondary education has a positive effect on the public awareness on the role of physical activity in human life. In general, the analysis of the research indicates that there is a relationship between physical activity and some socio-economic factors of the respondents, such as gender, age, education, marital status, income per capita, and the possession of savings. Although the obtained results cannot be applied for the general population, they show some important trends that will be verified in subsequent studies conducted by the authors of the paper.

Keywords: IPAQ, nonmanual workers, physical activity, socioeconomic factors, WHO

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Authors: Zuzana Tatarkova, Ivana Pilchova, Michal Cibulka, Martin Kolisek, Peter Racay, Peter Kaplan

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Introduction: Normal functioning of mitochondria is crucial for cardiac performance. Mitochondria undergo mitophagy and biogenesis, and mitochondrial proteins are subject to extensive post-translational modifications. The state of mitochondrial homeostasis reflects overall cellular fitness and longevity. Perturbed mitochondria produce less ATP, release greater amounts of reactive molecules, and are more prone to apoptosis. Therefore mitochondrial turnover is an integral aspect of quality control in which dysfunctional mitochondria are selectively eliminated through mitophagy. Currently, the progressive deterioration of physiological functions is seen as accumulation of modified/damaged proteins with limiting regenerative ability and disturbance of such affected protein-protein communication throughout aging in myocardial cells. Methodologies: For our study was used immunohistochemistry, biochemical methods: spectrophotometry, western blotting, immunodetection as well as more sophisticated 2D electrophoresis and mass spectrometry for evaluation protein-protein interactions and specific post-translational modification. Results and Discussion: Mitochondrial stress response to reactive species was evaluated as electron transport chain (ETC) complexes, redox-active molecules, and their possible communication. Protein-protein interactions revealed a strong linkage between age and ETC protein subunits. Redox state was strongly affected in senescent mitochondria with shift in favor of more pro-oxidizing condition within cardiomyocytes. Acute myocardial ischemia and ischemia-reperfusion (IR) injury affected ETC complexes I, II and IV with no change in complex III. Ischemia induced decrease in total antioxidant capacity, MnSOD, GSH and catalase activity with recovery in some extent during reperfusion. While MnSOD protein content was higher in IR group, activity returned to 95% of control. Nitric oxide is one of the biological molecules that can out compete MnSOD for superoxide and produce peroxynitrite. This process is faster than dismutation and led to the 10-fold higher production of nitrotyrosine after IR injury in adult with higher protection in senescent ones. 2D protein profiling revealed 140 mitochondrial proteins, 12 of them with significant changes after IR injury and 36 individual nitrotyrosine-modified proteins further identified by mass spectrometry. Linking these two groups, 5 proteins were altered after IR as well as nitrated, but only one showed massive nitration per lowering content of protein after IR injury in adult. Conclusions: Senescent cells have greater proportion of protein content, which might be modulated by several post-translational modifications. If these protein modifications are connected to functional consequences and protein-protein interactions are revealed, link may lead to the solution. Assume all together, dysfunctional proteostasis can play a causative role and restoration of protein homeostasis machinery is protective against aging and possibly age-related disorders. This work was supported by the project VEGA 1/0018/18 and by project 'Competence Center for Research and Development in the field of Diagnostics and Therapy of Oncological diseases', ITMS: 26220220153, co-financed from EU sources.

Keywords: aging heart, mitochondria, proteomics, redox state

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Authors: Jagmeet S. Kanwal, Julia F. Langley

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Music can heal the body, but a mechanistic understanding of this phenomenon is lacking. This study explores the effects of music presentation on neurologic and physiologic responses leading to metabolic changes in the human body. The mind and body co-exist in a corporeal entity and within this framework, sickness ensues when the mind-body balance goes awry. It is further hypothesized that music has the capacity to directly reset this balance. Two lines of inquiry taken together can provide a mechanistic understanding of this phenomenon 1) Empirical evidence for a sound-sensitive pressure sensor system in the body, and 2) The notion of a “healing center” within the brain that is activated by specific patterns of sounds. From an acoustics perspective, music is spatially distributed as pressure waves ranging from a few cm to several meters in wavelength. These waves interact and propagate in three-dimensions in unique ways, depending on the wavelength. Furthermore, music creates dynamically changing wave-fronts. Frequencies between 200 Hz and 1 kHz generate wavelengths that range from 5'6" to 1 foot. These dimensions are in the range of the body size of most people making it plausible that these pressure waves can geometrically interact with the body surface and create distinct patterns of pressure stimulation across the skin surface. For humans, short wavelength, high frequency (> 200 Hz) sounds are best received via cochlear receptors. For low frequency (< 200 Hz), long wavelength sound vibrations, however, the whole body may act as an ideal receiver. A vast array of highly sensitive pressure receptors (Pacinian corpuscles) is present just beneath the skin surface, as well as in the tendons, bones, several organs in the abdomen, and the sexual organs. Per the available empirical evidence, these receptors contribute to music perception by allowing the whole body to function as a sound receiver, and knowledge of how they function is essential to fully understanding the therapeutic effect of music. Neuroscientific studies have established that music stimulates the limbic system that can trigger states of anxiety, arousal, fear, and other emotions. These emotional states of brain activity play a crucial role in filtering top-down feedback from thoughts and bottom-up sensory inputs to the autonomic system, which automatically regulates bodily functions. Music likely exerts its pleasurable and healing effects by enhancing functional and effective connectivity and feedback mechanisms between brain regions that mediate reward, autonomic, and cognitive processing. Stimulation of pressure receptors under the skin by low-frequency music-induced sensations can activate multiple centers in the brain, including the amygdala, the cingulate cortex, and nucleus accumbens. Melodies in music in the low (< 600 Hz) frequency range may augment auditory inputs after convergence of the pressure-sensitive inputs from the vagus nerve onto emotive processing regions within the limbic system. The integration of music-generated auditory and somato-visceral inputs may lead to a synergistic input to the brain that promotes healing. Thus, music can literally heal humans through “touch” as it energizes the brain’s autonomic system for restoring homeostasis.

Keywords: acoustics, brain, music healing, pressure receptors

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

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

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

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Authors: Natalia Hordynska, Magdalena Szechynska-Hebda, Miroslaw Sobczak, Elzbieta Rozanska, Joanna Troczynska, Zofia Banaszak, Maria Wedzony

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Albinism is a common problem encountered in wheat and triticale breeding programs, which require in vitro culture steps e.g. generation of doubled haploids via androgenesis process. Genetic factor is a major determinant of albinism, however, environmental conditions such as temperature and media composition influence the frequency of albino plant formation. Cold incubation of wheat and triticale spikes induced a switch from gametophytic to sporophytic development. Further, androgenic structures formed from anthers of the genotypes susceptible to androgenesis or treated with cold stress, had a pool of structurally primitive plastids, with small starch granules or swollen thylakoids. High temperature was a factor inducing andro-genesis of wheat and triticale, but at the same time, it was a factor favoring the formation of albino plants. In genotypes susceptible to albinism or after heat stress conditions, cells formed from anthers were vacuolated, and plastids were eliminated. Partial or complete loss of chlorophyll pigments and incomplete differentiation of chloroplast membranes result in formation of tissues or whole plant unable to perform photosynthesis. Indeed, susceptibility to the andro-genesis process was associated with an increase of total concentration of photosynthetic pigments in anthers, spikes and regenerated plants. The proper balance of the synthesis of various pigments, was the starting point for their proper incorporation into photosynthetic membranes. In contrast, genotypes resistant to the androgenesis process and those treated with heat, contained 100 times lower content of photosynthetic pigments. In particular, the synthesis of violaxanthin, zeaxanthin, lutein and chlorophyll b was limited. Furthermore, deregulation of starch and lipids synthesis, which led to the formation of very complex starch granules and an increased number of oleosomes, respectively, correlated with the reduction of the efficiency of androgenesis. The content of other sugars varied depending on the genotype and the type of stress. The highest content of various sugars was found for genotypes susceptible to andro-genesis, and highly reduced for genotypes resistant to androgenesis. The most important sugars seem to be glucose and fructose. They are involved in sugar sensing and signaling pathways, which affect the expression of various genes and regulate plant development. Sucrose, on the other hand, seems to have minor effect at each stage of the androgenesis. The sugar metabolism was related to metabolic activity of microspores. The genotypes susceptible to androgenesis process had much faster mitochondrium- and chloroplast-dependent energy conversion and higher heat production by tissues. Thus, the effectiveness of metabolic processes, their balance and the flexibility under the stress was a factor determining the direction of microspore development, and in the later stages of the androgenesis process, a factor supporting the induction of androgenic structures, chloroplast formation and the regeneration of green plants. The work was financed by Ministry of Agriculture and Rural Development within Program: ‘Biological Progress in Plant Production’, project no HOR.hn.802.15.2018.

Keywords: androgenesis, chloroplast, metabolism, temperature stress

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Authors: Agata Migdalska, Joanna Berczynska, Ewa Bieniek, Jacek Sterna

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Muscle relaxation is considered important during general anesthesia for spine stabilization. In a presented case peripherally acting muscle relaxant was applied during general anesthesia for spine stabilization surgery. The patient was a dog, 11-years old, 26 kg, male, mix breed. Spine fracture was situated between Th13-L1-L2, probably due to the car accident. Preanesthetic physical examination revealed no sign underlying health issues. The dog was premedicated with midazolam 0.2 mg IM and butorphanol 2.4 mg IM. General anesthesia was induced with propofol IV. After the induction, the dog was intubated with an endotracheal tube and connected to an open-ended rebreathing system and maintained with the use of inhalation anesthesia with isoflurane in oxygen. 0,5 mg/ kg of rocuronium was given IV. Use of muscle relaxant was accompanied by an assessment of the degree of neuromuscular blockade by peripheral nerve stimulator. Electrodes were attached to the skin overlying at the peroneal nerve at the lateral cranial tibia. Four electrical pulses were applied to the nerve over a 2 second period. When satisfying nerve block was detected dog was prepared for the surgery. No further monitoring of the effectiveness of blockade was performed during surgery. Mechanical ventilation was kept during anesthesia. During surgery dog maintain stable, and no anesthesiological complication occur. Intraoperatively surgeon claimed that neuromuscular blockade results in a better approach to the spine and easier muscle manipulation which was helpful in order to see the fracture and replace bone fragments. Finally, euthanasia was performed intraoperatively as a result of vast myelomalacia process of the spinal cord. This prevented examination of the recovering process. Neuromuscular blocking agents act at the neuromuscular junction to provide profound muscle relaxation throughout the body. Muscle blocking agents are neither anesthetic nor analgesic; therefore inappropriately used may cause paralysis in fully conscious and feeling pain patient. They cause paralysis of all skeletal muscles, also diaphragm and intercostal muscles when given in higher doses. Intraoperative management includes maintaining stable physiological conditions, which involves adjusting hemodynamic parameters, ensuring proper ventilation, avoiding variations in temperature, maintain normal blood flow to promote proper oxygen exchange. Neuromuscular blocking agent can cause many side effects like residual paralysis, anaphylactic or anaphylactoid reactions, delayed recovery from anesthesia, histamine release, recurarization. Therefore reverse drug like neostigmine (with glikopyrolat) or edrofonium (with atropine) should be used in case of a life-threatening situation. Another useful drug is sugammadex, although the cost of this drug strongly limits its use. Muscle relaxant improves surgical conditions during spinal surgery, especially in heavily muscled individuals. They are also used to facilitate the replacement of dislocated joints as they improve conditions during fracture reduction. It is important to emphasize that in a patient with muscle weakness neuromuscular blocking agents may result in intraoperative and early postoperative cardiovascular and respiratory complications, as well as prolonged recovery from anesthesia. This should not appear in patients with recent spine fracture or luxation. Therefore it is believed that neuromuscular blockers could be useful during spine stabilization procedures.

Keywords: anesthesia, dog, neuromuscular block, spine surgery

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Authors: Joshua Kaufman, Felix Tan, Morgan Monroe, Ayman Abouraddy

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Textiles and clothing have been a staple of human existence for millennia, yet the basic structure and functionality of textile fibers and yarns has remained unchanged. While color and appearance are essential characteristics of a textile, an advancement in the fabrication of yarns that allows for user-controlled dynamic changes to the color or appearance of a garment has been lacking. Touch-activated and photosensitive pigments have been used in textiles, but these technologies are passive and cannot be controlled by the user. The technology described here allows the owner to control both when and in what pattern the fabric color-change takes place. In addition, the manufacturing process is compatible with mass-producing the user-controlled, color-changing yarns. The yarn fabrication utilizes a fiber spinning system that can produce either monofilament or multifilament yarns. For products requiring a more robust fabric (backpacks, purses, upholstery, etc.), larger-diameter monofilament yarns with a coarser weave are suitable. Such yarns are produced using a thread-coater attachment to encapsulate a 38-40 AWG metal wire inside a polymer sheath impregnated with thermochromic pigment. Conversely, products such as shirts and pants requiring yarns that are more flexible and soft against the skin comprise multifilament yarns of much smaller-diameter individual fibers. Embedding a metal wire in a multifilament fiber spinning process has not been realized to date. This research has required collaboration with Hills, Inc., to design a liquid metal-injection system to be combined with fiber spinning. The new system injects molten tin into each of 19 filaments being spun simultaneously into a single yarn. The resulting yarn contains 19 filaments, each with a tin core surrounded by a polymer sheath impregnated with thermochromic pigment. The color change we demonstrate is distinct from garments containing LEDs that emit light in various colors. The pigment itself changes its optical absorption spectrum to appear a different color. The thermochromic color-change is induced by a temperature change in the inner metal wire within each filament when current is applied from a small battery pack. The temperature necessary to induce the color change is near body temperature and not noticeable by touch. The prototypes already developed either use a simple push button to activate the battery pack or are wirelessly activated via a smart-phone app over Wi-Fi. The app allows the user to choose from different activation patterns of stripes that appear in the fabric continuously. The power requirements are mitigated by a large hysteresis in the activation temperature of the pigment and the temperature at which there is full color return. This was made possible by a collaboration with Chameleon International to develop a new, customized pigment. This technology enables a never-before seen capability: user-controlled, dynamic color and pattern change in large-area woven and sewn textiles and fabrics with wide-ranging applications from clothing and accessories to furniture and fixed-installation housing and business décor. The ability to activate through Wi-Fi opens up possibilities for the textiles to be part of the ‘Internet of Things.’ Furthermore, this technology is scalable to mass-production levels for wide-scale market adoption.

Keywords: activation, appearance, color, manufacturing

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Authors: Hannah R. Devens, Phillip L. Davidson, Dione Deaker, Kathryn E. Smith, Gregory A. Wray, Maria Byrne

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Marine invertebrate species with calcifying larvae are especially vulnerable to ocean acidification (OA) caused by rising atmospheric CO₂ levels. Acidic conditions can delay development, suppress metabolism, and decrease the availability of carbonate ions in the ocean environment for skeletogenesis. These stresses often result in increased larval mortality, which may lead to significant ecological consequences including alterations to the larval settlement, population distribution, and genetic connectivity. Importantly, many of these physiological and developmental effects are caused by genetic and molecular level changes. Although many studies have examined the effect of near-future oceanic pH levels on gene expression in marine invertebrates, little is known about the impact of OA on gene expression in a developmental context. Here, we performed mRNA-sequencing to investigate the impact of environmental acidity on gene expression across three developmental stages in the sea urchin Heliocidaris erythrogramma. We collected RNA from gastrula, early larva, and 1-day post-metamorphic juvenile sea urchins cultured at present-day and predicted future oceanic pH levels (pH 8.1 and 7.7, respectively). We assembled an annotated reference transcriptome encompassing development from egg to ten days post-metamorphosis by combining these data with datasets from two previous developmental transcriptomic studies of H. erythrogramma. Differential gene expression and time course analyses between pH conditions revealed significant alterations to developmental transcription that are potentially associated with pH stress. Consistent with previous investigations, genes involved in biomineralization and ion transport were significantly upregulated under acidic conditions. Differences in gene expression between the two pH conditions became more pronounced post-metamorphosis, suggesting a development-dependent effect of OA on gene expression. Furthermore, many differences in gene expression later in development appeared to be a result of broad downregulation at pH 7.7: of 539 genes differentially expressed at the juvenile stage, 519 of these were lower in the acidic condition. Time course comparisons between pH 8.1 and 7.7 samples also demonstrated over 500 genes were more lowly expressed in pH 7.7 samples throughout development. Of the genes exhibiting stage-dependent expression level changes, over 15% of these diverged from the expected temporal pattern of expression in the acidic condition. Through these analyses, we identify novel candidate genes involved in development, metabolism, and transcriptional regulation that are possibly affected by pH stress. Our results demonstrate that pH stress significantly alters gene expression dynamics throughout development. A large number of genes differentially expressed between pH conditions in juveniles relative to earlier stages may be attributed to the effects of acidity on transcriptional regulation, as a greater proportion of mRNA at this later stage has been nascent transcribed rather than maternally loaded. Also, the overall downregulation of many genes in the acidic condition suggests that OA-induced developmental delay manifests as suppressed mRNA expression, possibly from lower transcription rates or increased mRNA degradation in the acidic environment. Further studies will be necessary to determine in greater detail the extent of OA effects on early developing marine invertebrates.

Keywords: development, gene expression, ocean acidification, RNA-sequencing, sea urchins

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Authors: Osman Adiguzel

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Shape-memory alloys are a new class of functional materials with a peculiar property known as shape memory effect. These alloys return to a previously defined shape on heating after deformation in low temperature product phase region and take place in a class of functional materials due to this property. The origin of this phenomenon lies in the fact that the material changes its internal crystalline structure with changing temperature. Shape memory effect is based on martensitic transitions, which govern the remarkable changes in internal crystalline structure of materials. Martensitic transformation, which is a solid state phase transformation, occurs in thermal manner in material on cooling from high temperature parent phase region. This transformation is governed by changes in the crystalline structure of the material. Shape memory alloys cycle between original and deformed shapes in bulk level on heating and cooling, and can be used as a thermal actuator or temperature-sensitive elements due to this property. Martensitic transformations usually occur with the cooperative movement of atoms by means of lattice invariant shears. The ordered parent phase structures turn into twinned structures with this movement in crystallographic manner in thermal induced case. The twinned martensites turn into the twinned or oriented martensite by stressing the material at low temperature martensitic phase condition. The detwinned martensite turns into the parent phase structure on first heating, first cycle, and parent phase structures turn into the twinned and detwinned structures respectively in irreversible and reversible memory cases. On the other hand, shape memory materials are very important and useful in many interdisciplinary fields such as medicine, pharmacy, bioengineering, metallurgy and many engineering fields. The choice of material as well as actuator and sensor to combine it with the host structure is very essential to develop main materials and structures. Copper based alloys exhibit this property in metastable beta-phase region, which has bcc-based structures at high temperature parent phase field, and these structures martensitically turn into layered complex structures with lattice twinning following two ordered reactions on cooling. Martensitic transition occurs as self-accommodated martensite with inhomogeneous shears, lattice invariant shears which occur in two opposite directions, <110 > -type directions on the {110}-type plane of austenite matrix which is basal plane of martensite. This kind of shear can be called as {110}<110> -type mode and gives rise to the formation of layered structures, like 3R, 9R or 18R depending on the stacking sequences on the close-packed planes of the ordered lattice. In the present contribution, x-ray diffraction and transmission electron microscopy (TEM) studies were carried out on two copper based alloys which have the chemical compositions in weight; Cu-26.1%Zn 4%Al and Cu-11%Al-6%Mn. X-ray diffraction profiles and electron diffraction patterns reveal that both alloys exhibit super lattice reflections inherited from parent phase due to the displacive character of martensitic transformation. X-ray diffractograms taken in a long time interval show that locations and intensities of diffraction peaks change with the aging time at room temperature. In particular, some of the successive peak pairs providing a special relation between Miller indices come close each other.

Keywords: Shape memory effect, martensite, twinning, detwinning, self-accommodation, layered structures

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Authors: Turky Al-Qahtani, Roustem Miftahof

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Introduction: Under common assumptions of excitabi-lity, morphological (cellular) homogeneity, and spatial structural anomalies added as required, it has been shown that biological systems are able to display travelling wave dynamics. Being not self-sustainable, existence depends on the electrophysiological state of transmembrane ion channels and it requires an extrinsic/intrinsic periodic source. However, organs in the body are highly multicellular, heterogeneous, and their functionality is the outcome of electro-mechanical conjugation, rather than excitability only. Thus, peristalsis in the gut relies on spatiotemporal myoelectrical pattern formations between the mechanical, represented by smooth muscle cells (SM), and the control, comprised of a chain of primary sensory and motor neurones, components. Synaptically linked through the afferent and efferent pathways, they form a functional unit (FU) of the gut. Aims: These are: i) to study numerically the complex dynamics, and ii) to investigate the possibility of self-sustained myoelectrical activity in the FU. Methods: The FU recreates the following sequence of physiological events: deformation of mechanoreceptors of located in SM; generation and propagation of electrical waves of depolarisation - spikes - along the axon to the soma of the primary neurone; discharge of the primary neurone and spike propagation towards the motor neurone; burst of the motor neurone and transduction of spikes to SM, subsequently producing forces of contraction. These are governed by a system of nonlinear partial and ordinary differential equations being a modified version of the Hodgkin-Huxley model and SM fibre mechanics. In numerical experiments; the source of excitation is mechanical stretches of SM at a fixed amplitude and variable frequencies. Results: Low frequency (0.5 < v < 2 Hz) stimuli cause the propagation of spikes in the neuronal chain and, finally, the generation of active forces by SM. However, induced contractions are not sufficient to initiate travelling wave dynamics in the control system. At frequencies, 2 < v < 4 Hz, multiple low amplitude and short-lasting contractions are observed in SM after the termination of stretching. For frequencies (0.5 < v < 4 Hz), primary and sensory neurones demonstrate strong connectivity and coherent electrical activity. Significant qualitative and quantitative changes in dynamics of myoelectical patterns with a transition to a self-organised mode are recorded with the high degree of stretches at v = 4.5 Hz. Increased rates of deformation lead to the production of high amplitude signals at the mechanoreceptors with subsequent self-sustained excitation within the neuronal chain. Remarkably, the connection between neurones weakens resulting in incoherent firing. Further increase in a frequency of stimulation (v > 4.5 Hz) has a detrimental effect on the system. The mechanical and control systems become disconnected and exhibit uncoordinated electromechanical activity. Conclusion: To our knowledge, the existence of periodic activity in a multicellular, functionally heterogeneous biological system with mechano-electrical dynamics, such as the FU, has been demonstrated for the first time. These findings support the notion of possible peristalsis in the gut even in the absence of intrinsic sources - pacemaker cells. Results could be implicated in the pathogenesis of intestinal dysrythmia, a medical condition associated with motor dysfunction.

Keywords: complex dynamics, functional unit, the gut, dysrythmia

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Authors: Tugba Altin

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

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

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Authors: Ashleigh Williams

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Micro- and nanoplastics’ (MNLPs) omnipresence and ecological accumulation is evident when surveying recent environmental impact studies. For example, in 2014 it was estimated that at least 52.3 trillion plastic microparticles are floating at sea, and scientists have even found plastics present remote Arctic ice and snow (5,6). Plastics have even found their way into precipitation, with more than 1000 tons of microplastic rain precipitating onto the Western United States in 2020. Even more recent studies evaluating the chemical safety of reusable plastic bottles found that hundreds of chemicals leached into the control liquid in the bottle (ddH2O, ph = 7) during a 24-hour time period. A consequence of the increased abundance in plastic waste in the air, land, and water every year is the bioaccumulation of MNLPs in ecosystems and trophic niches of the animal food chain, which could potentially cause increased direct and indirect exposure of humans to MNLPs via inhalation, ingestion, and dermal contact. Though the detrimental, toxic effects of MNLPs have been established in marine biota, much less is known about the potentially hazardous health effects of chronic MNLP ingestion in humans. Recent data indicate that long-term exposure to MNLPs could cause possible inflammatory and dysbiotic effects. However, toxicity seems to be largely dose-, as well as size-dependent. In addition, the transcytotic uptake of MNLPs through the intestinal epithelia in humans remain relatively unknown. To this point, the goal of the current study was to investigate the mechanisms of micro- and nanoplastic uptake and transcytosis of Polystyrene (PE) in human stem-cell derived, physiologically relevant in vitro intestinal model systems, and to compare the relative effect of particle size (30 nm, 100 nm, 500 nm and 1 µm), and concentration (0 µg/mL, 250 µg/mL, 500 µg/mL, 1000 µg/mL) on polystyrene MNLP uptake, transcytosis and intestinal epithelial model integrity. Observational and quantitative data obtained from confocal microscopy, immunostaining, transepithelial electrical resistance (TEER) measurements, cryosectioning, and ELISA cytokine assays of the proinflammatory cytokines Interleukin-6 and Interleukin-8 were used to evaluate the localization and transcytosis of polystyrene MNPs and its impact on epithelial integrity in human-derived intestinal in vitro model systems. The effect of Microfold (M) cell induction on polystyrene micro- and nanoparticle (MNP) uptake, transcytosis, and potential inflammation was also assessed and compared to samples grown under standard conditions. Microfold (M) cells, link the human intestinal system to the immune system and are the primary cells in the epithelium responsible for sampling and transporting foreign matter of interest from the lumen of the gut to underlying immune cells. Given the uptake capabilities of Microfold cells to interact both specifically and nonspecific to abiotic and biotic materials, it was expected that M- cell induced in vitro samples would have increased binding, localization, and potentially transcytosis of Polystyrene MNLPs across the epithelial barrier. Experimental results of this study would not only help in the evaluation of the plastic toxicity, but would allow for more detailed modeling of gut inflammation and the intestinal immune system.

Keywords: nanoplastics, enteroids, intestinal barrier, tissue engineering, microfold (M) cells

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Authors: Georges F. Hatoum, Thomas H. Temple, Silvio Garcia, Xiaodong Wu

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Soft Tissue Sarcomas (STS) represent a diverse group of malignancies with heterogeneous clinical and pathological features. The treatment of extremity STS aims to achieve optimal local tumor control, improved survival, and preservation of limb function. The National Comprehensive Cancer Network guidelines, based on the cumulated clinical data, recommend radiation therapy (RT) in conjunction with limb-sparing surgery for large, high-grade STS measuring greater than 5 cm in size. Such treatment strategy can offer a cure for patients. However, when recurrence occurs (in nearly half of patients), the prognosis is poor, with a median survival of 12 to 15 months and with only palliative treatment options available. The spatially-fractionated-radiotherapy (SFRT), with a long history of treating bulky tumors as a non-mainstream technique, has gained new attention in recent years due to its unconventional therapeutic effects, such as bystander/abscopal effects. Combining single fraction of GRID, the original form of SFRT, with conventional RT was shown to have marginally increased the rate of pathological necrosis, which has been recognized to have a positive correlation to overall survival. In an effort to consistently increase the pathological necrosis rate over 90%, multiple fractions of Lattice RT (LRT), a newer form of 3D SFRT, interdigitated with the standard RT as neoadjuvant therapy was conducted in a preliminary clinical setting. With favorable results of over 95% of necrosis rate in a small cohort of patients, a Phase I/II clinical study was proposed to exam the safety and feasibility of this new strategy. Herein the design of the clinical study is presented. In this single-arm, two-stage phase I/II clinical trial, the primary objectives are >80% of the patients achieving >90% tumor necrosis and to evaluation the toxicity; the secondary objectives are to evaluate the local control, disease free survival and overall survival (OS), as well as the correlation between clinical response and the relevant biomarkers. The study plans to accrue patients over a span of two years. All patient will be treated with the new neoadjuvant RT regimen, in which one of every five fractions of conventional RT is replaced by a LRT fraction with vertices receiving dose ≥10Gy while keeping the tumor periphery at or close to 2 Gy per fraction. Surgical removal of the tumor is planned to occur 6 to 8 weeks following the completion of radiation therapy. The study will employ a Pocock-style early stopping boundary to ensure patient safety. The patients will be followed and monitored for a period of five years. Despite much effort, the rarity of the disease has resulted in limited novel therapeutic breakthroughs. Although a higher rate of treatment-induced tumor necrosis has been associated with improved OS, with the current techniques, only 20% of patients with large, high-grade tumors achieve a tumor necrosis rate exceeding 50%. If this new neoadjuvant strategy is proven effective, an appreciable improvement in clinical outcome without added toxicity can be anticipated. Due to the rarity of the disease, it is hoped that such study could be orchestrated in a multi-institutional setting.

Keywords: lattice RT, necrosis, SFRT, soft tissue sarcoma

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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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