Cell Radius Research Articles

Calculation of alpha particle single-event spectra using a neural network.

A neural network was trained to accurately predict the entire single-event specific energy spectra for use in alpha-particle microdosimetry calculations. The network consisted of 4 inputs and 21 outputs and was trained on data calculated using Monte Carlo simulation where input parameters originated both from previously published data as well as randomly generated parameters that fell within a target range. The 4 inputs consisted of the source-target configuration (consisting of both cells in suspension and in tissue-like geometries), alpha particle energy (3.97-8.78 MeV), nuclei radius (2-10 μm), and cell radius (2.5-20 μm). The 21 output values consisted of the maximum specific energy (zmax), and 20 values of the single-event spectra, which were expressed as fractional values of zmax. The neural network consisted of two hidden layers with 10 and 26 nodes, respectively, with the loss function characterized as the mean square error (MSE) between the actual and predicted values for zmax and the spectral outputs. For the final network, the root mean square error (RMSE) values of zmax for training, validation and testing were 1.57 x10-2, 1.51 x 10-2 and 1.35 x 10-2, respectively. Similarly, the RMSE values of the spectral outputs were 0.201, 0.175 and 0.199, respectively. The correlation coefficient, R2, was > 0.98 between actual and predicted values from the neural network. In summary, the network was able to accurately reproduce alpha-particle single-event spectra for a wide range of source-target geometries.

CYTOSKELETON DYNAMICS AND SPATIAL ORGANIZATION DURING EPITHELIAL-TO-MESENCHYMAL TRANSITION

Epithelial-to-mesenchymal transition (EMT) is a crucial process that occurs during normal development, such as embryogenesis and organ formation. If it is inappropriately activated, it can lead to pathological processes like metastasis. Although EMT is well studied at the morphological and transcriptome level, cytoskeleton changes during this process are less understood. In our work we aimed to describe the morphological changes that occurred in MCF-7, A-549 and HaCaT cells after EMT, analyze microtubule dynamics, spatial distribution and its contribution to cell motility, identify changes in actin filament organization and study focal adhesion turnover in the cells after EMT. We hypothesized that the dynamics of microtubules in cells undergoing EMT might change. Cells undergoing EMT were expected to have more dynamic microtubules. Also, cells undergoing EMT are expected to adhere more efficiently to diverse substrates, and therefore spread and move more easily. Focal contacts in cells undergoing EMT were expected to be more pronounced and dynamic than in cells that not undergoing EMT. The research methods used in the study included inducing EMT in modified MCF-7 cells through an inserted inducible Tet-on system and stimulation of EMT in A-549 and HaCaT cells using TGF-β. The cells were observed using bright field microscopy, and immunofluorescence analysis was conducted to visualize microtubules and actin filaments. Transfection with EB-3–RFP protein was done to describe and measure microtubule dynamics, while transduction with Talin-RFP and transient transfection with Ptag-RFP-vinculin was done to visualize focal adhesions. Time-lapse fluorescent microscopy was used to record films, and the Fiji Image J program was used to analyze the data. All statistical analysis was performed using GraphPad Prism (Dotmatics, USA), and a nonparametric Mann-Whitney U test or parametric t-test with Welch correction. The actin filament measurements were completed using Matlab scripts. The major research findings: In all three-cell models after EMT, cell morphology changed. Cells increased in size. MCF-7 and HaCaT became spread out, while A-549 became elongated. Some of the cells lost cell-cell contacts. All three cell models after EMT had alterations in microtubule organization and dynamics. MCF-7 and HaCaT cells showed more frequently individual MTs at cell edges, while A-549 had less covered nucleus by MTs after EMT. Microtubule dynamics (growth velocity) increased, and the length of microtubule growth tracks became longer. The average angle of MT growth trajectories to cell radius decreased. Actin fibers rearranged into more pronounced stress fibers after EMT. Alterations in the focal adhesion behaviors were different in three models used. These results indicate that cytoskeletal changes during EMT mainly include increased microtubule dynamics.

Incorporating boron distribution variations in microdosimetric kinetic model-based relative biological effectiveness calculations for boron neutron capture therapy.

This study introduces the MKM_B model, an approach derived from the MKM model, designed to evaluate the biological effectiveness of Boron Neutron Capture Therapy (BNCT) in the face of challenges from varying microscopic boron distributions. The model introduces a boron compensation factor, allowing for the assessment of compound Biological Effectiveness (CBE) values for different boron distributions. Utilizing the TOPAS simulation platform, the lineal energy spectrum of particles in BNCT was simulated, and the sensitivity of the MKM_B model to parameter variations and the influence of cell size on the model were thoroughly investigated. The CBE values for 10B-boronphenylalanine (BPA) and 10B-sodium (BSH) were determined to be 3.70 and 1.75, respectively. These calculations were based on using the nucleus radius of 2.5 μm and the cell radius of 5 μm while considering a 50% surviving fraction. It was observed that as cell size decreased, the CBE values for both BPA and BSH increased. Additionally, the model parameter rd was identified as having the most significant impact on CBE, with other parameters showing moderate effects. The development of the MKM_B model enables the accurate prediction of CBE under different boron distributions in BNCT. This model offers a promising approach to optimize treatment planning by providing increased accuracy in biological effectiveness.

Evaluation of Scatterer Parameters From Ultrasound Scattering Models Taking Into Account Scattering From Nuclei and Cells of Cell-Pellet Biophantoms and Ex Vivo Tumors.

The Quantitative Ultrasound backscatter coefficient provides the capability to evaluate tissue microstructure parameters. Tissue-based scatterer parameters are extracted using ultrasound scattering models. It is challenging to correlate ultrasound scatterer parameters of tissue structures from optical-measured histology, possibly because of inappropriate scattering models or the presence of multiple scatterers. The objective of this study is to pursue the quantification of pertinent scatterer parameters with scattering models that consider ultrasound scattering from nuclei and cells. The concentric sphere model (CSM) and the structure factor model adapted for two types of scatterers (SFM2) are evaluated for cell-pellet biophantoms and ex vivo tumors of four cell lines: 4T1, JC, LMTK, and MAT. The structure factor model (SFM) was used for comparison. CSM and SFM2 provided scatterer parameters closer to histology (lower relative errors) for nucleus and cell radii and volume fractions than SFM but were not always accompanied by lower dispersion of the scatterer distribution (lower coefficient of variation). CSM and SFM2 quantified cell and nucleus radius and volume fraction parameters with lower relative error compared to SFM. For tumors, CSM provided better results than SFM2.

Assessment of 3D printed mechanical metamaterials for prosthetic liners.

This study focuses on novel design and evaluation of Elastic 50A (EL50) mechanical metamaterials with open-cell patterns for its potential application to lower limb residuum/socket interfaces, specifically that of a transtibial (TT) amputee. Mechanical characteristics, that is, effective Young's modulus (E), was tuned by altering metamaterial porosity, which was experimentally verified. Specifically, pore radius of the unit cell was varied to achieve a range of E-values (0.05-1.71 MPa) for these 3D printed metamaterials. Finite Element Analysis (FEA) was conducted to evaluate pressure distribution across key load-bearing anatomical sites of a TT residuum. Using designed metamaterials for homogeneous liners, pressure profiles were studied and compared with a silicone liner case. Additionally, a custom metamaterial liner was designed by assigning appropriate metamaterials to four load-sensitive and tolerant anatomical sites of the TT residuum. The results suggest that lowest pressure variation (PV), as a measure of pressure distribution levels and potential comfort for amputees, was achieved by the custom metamaterial liner compared to any of the homogeneous liners included in this study. It is envisaged that this work may aid future design and development of custom liners using now commonly available 3D printing technologies and available elastomer materials to maximise comfort, tissue safety and overall rehabilitation outcomes for lower limb amputees.

An anisotropic PRS for squinting the radiation pattern with gain improvement of MIMO system

This work presents the design and analysis of a new anisotropic Partial Reflective Surface (PRS) to address beam squinting as well as gain improvement, using the phase gradient property of periodic structure in a 3-port Multiple Input Multiple Output (MIMO) system. An angular tilt of 30° is obtained relative to the boresight direction by manipulating the transmission properties. Additionally, the gain is improved by utilizing a homogenous PRS. Gradation constant is realized by changing the radius of adjacent unit cells in a dielectric host structure, ensuring a continuous variation in PRS properties. The formation of a Fabry-Perot antenna reduces the overlap between the adjacent beams, improving field correlation and isolation performance, in addition to gain enhancement. Furthermore, two 1 × 5 absorbers are strategically placed between the radiating elements to minimize the surface currents and achieve high port isolation. This combination of PRS and absorber leads to reduced field-to-field coupling and port-to-port coupling, thus achieving high signal isolation and beam squinting accuracy. The effectiveness of the proposed approach is validated through simulations, which are further supported by an equivalent circuit model. Experimental validation is also conducted to verify the results obtained.

Abstract C018: Spatial profiling of tumor associated cells expressing endoplasmic reticulum stress proteins predicts poor outcomes in pancreatic cancer patients

Abstract The crosstalk between pancreatic cancer (PC) cells and cells of the tumor microenvironment (TME), such as immune cells and cancer associated fibroblasts (CAFs), has important implications for tumor progression. It is evident that the expression of endoplasmic reticulum (ER) stress proteins (e.g., BiP or CHOP) in tumor cells has survival implications for patients. For example, high BiP expression in tumor cells is correlated with poor survival in PC patients. However, the effect of these proteins in TME cells is currently unknown. We have employed quantitative multiplex immunofluorescence on a tumor microarray cohort of 259 treatment naive pancreatic cancer patient samples and 41 normal pancreas samples. We investigated the impact of expression of ER stress proteins BiP or CHOP in CAFS (α-SMA+), immune cells (CD45+), endothelial cells (CD31+) and tumor cells (PanCK+). HALO AI (Indica Labs) was used to conduct cell/tissue classifications and spatial proximity analysis. Notably, the proportion of CAFs and endothelial cells expressing BiP or CHOP was significantly (p<0.01-0.0001) increased in tumor sections compared to non-tumor sections. When considering the tumor sections, increased BiP expression in CAFs and endothelial cells was found to be correlated with vascular invasion (p=0.0388 and p=0.0318 respectively). Interestingly, there was also a positive correlation between the percent of total CAFs and the percent of BiP positive cells (p=0.0037, r=0.293) or CHOP positive cells (p=0.0001, r=0.235), suggesting that ER stress could be associated with activation of CAFs. Spatial analysis was next utilized to explore the distribution of cells expressing BiP or CHOP within the TME. Remarkably, when examining the average distance in a 500 μm radius, our findings showed that immune cells expressing BiP or CHOP were located significantly (p<0.0001) closer to tumor cells compared to non-expressing immune cells. Interestingly, increased distance of CHOP expressing immune cells to tumor cells was negatively correlated (p=0.037, r=-0.137) with tumor size. We next examined these cells within a 20 μm radius of tumor cells, as it represents a physiologically feasible distance for direct cell-cell contact. Increased numbers of CHOP CD45 cells within the 20 μm radius was correlated with poorer overall survival (p=0.0062) and event free survival (p=0.046). Similarly, in CAFS, BiP expressing cells were found on average closer to tumor cells (p<0.0001), although this was not associated with patient survival. The observed correlation between elevated ER stress in TME cells with adverse patient outcomes indicates the importance of BiP or CHOP as potential therapeutic targets. Furthermore, the spatial analysis results provide insights into the organization of TME cells, shedding light on the significance of ER stress in the TME. These findings contribute to our understanding of the complex interplay between ER stress, tumor biology, and patient outcomes in PC. Citation Format: Georgia M. Porter, Murray Norris, Minoti Apte, Angelica Merlot. Spatial profiling of tumor associated cells expressing endoplasmic reticulum stress proteins predicts poor outcomes in pancreatic cancer patients [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C018.

Weakly nonlinear stability analysis of non-isothermal parallel flow in a vertical porous annulus

The study examines the stability of parallel airflow within a tall vertical coaxial circular annulus filled with a highly permeable porous medium under stable stratification. The linear stability theory predicts that the least unstable mode can be either axisymmetric or non-axisymmetric, depending on the values of the governing parameters. The curvature parameter, defined as the gap between coaxial circular cylinders, contributes to the stabilization of the flow. Depending on various controlling parameter values, the stably stratified non-isothermal annular parallel flow (SNAPF) can manifest three instability modes: thermal-shear, thermal-buoyant, and mixed or interactive. The instability type can change abruptly with Reynolds number, curvature parameter, and media permeability. A finite-amplitude instability analysis is examined using weakly nonlinear stability theory. The analysis demonstrates both subcritical and supercritical bifurcations near the instability boundary. The range of Reynolds numbers for subcritical bifurcation expands when switching from axisymmetric to non-axisymmetric disturbance. Bifurcation transitions between supercritical and subcritical occur due to changes in the least stable azimuthal mode. The study also investigates the equilibrium/threshold amplitude within the supercritical/subcritical instability regime, and it verifies the existence of subcritical/supercritical bifurcation through nonlinear kinetic energy balance. Furthermore, the finite-amplitude analysis anticipates that the lower critical Rayleigh number increases as the Reynolds number, curvature parameter, or media permeability decreases. An increase in the Reynolds number shifts the point of inflection in the velocity profile toward the inner cylinder, which subsequently leads to a reduction in the size of the core vortex region. In the subcritical instability regime, the radius of the primary vortex cell decreased significantly as the Rayleigh number increased. When the curvature is altered, a structural transition occurs in the isotherms from multicellular to unicellular.

Handoff performance analysis of PMIPv6‐based distributed mobility management protocol‐urban scenario

SummaryMobility management allows the networks to track down a mobile user's location for sending datagrams and to retain the connection when the user changes its location points repeatedly. Whenever a node switches between one base station and another, the connectivity is maintained through a process called handoff management. For real‐time traffic implementations in wireless network communications, handover performance is essential. A mobile node is blocked from transmitting and receiving a datagram for a longer time as the handover delay increases. Unacceptable handover delays are common in real‐time communication services. To guarantee smooth connectivity and continuous provision of services, effective handoff methods are required. The handoff efficiency of network‐based distributed mobility management (DMM) is studied extensively in this article, along with a comparison to PMIPv6. We specifically investigate how handover delay, session recovery, and packet loss are influenced by cell radius. From the analytical and simulation findings this paper concludes that network‐based DMM performs better than PMIPv6.

Analyzing battery thermal management systems: A comparative study of hydrogel and various PCMs in different configurations and convection conditions

No comprehensive analysis has been conducted to compare the performance of hydrogel- and phase change materials (PCMs)-based approaches for cooling lithium-ion batteries in the literature. The present study addresses this gap by comparing the effectiveness of hydrogel and various PCMs in two pack configurations: a fully-filled pack (Pack I) and a partially-filled pack (Pack II) in different convection conditions. While PCM-filled packs show no significant decrease in the cell temperature as a function of the distance between the cells, hydrogel-based cooling results in a significant decrease of 5.27 °C in the maximum temperature of the pack (Tmax) with increasing the distance from the cell radius to twice the cell radius. The study also finds that the effectiveness of latent heat in reducing the cell temperature decreases at higher melting temperatures. Among Packs I with small cell distances, n-Octadecane with the melting temperature of 28°C performs best with Tmax of 45.1 °C at the end of the cycles. However, for large cell distances (twice the cell radius), the hydrogel pack outperforms other cooling methods with a Tmax of 36.1 °C. In Packs II, at all cell distances, n-Octadecane is preferred. For hydrogel, at the end of the cycles, Tmax of Pack I is 3.0°C lower than that of Pack II under natural convection conditions. The study also reveals that Packs II with forced convection conditions are more effective than Packs I. Finally, the research shows that dispersing graphene nano-plates in n-Octadecane has an insignificant effect on the thermal behavior of the battery packs.

Regional differences in extracellular volume increase arrhythmia vulnerability in aortic stenosis patients with and without diffuse fibrosis: a computational study

Abstract Background Extracellular volume (ECV) determined by magnetic resonance imaging (MRI) is considered a marker of myocardial fibrosis and a predictor of mortality. In addition to diffuse fibrosis, aortic stenosis (AS) patients present increased ECV. However, the impact of regional ECV differences on arrhythmia vulnerability in AS patients has not been assessed. Purpose To investigate regional ECV differences in AS patients and to determine their impact on ventricular arrhythmia vulnerability. Methods MRI was performed in 51 AS patients (32 males, 19 females) before and 3 months after aortic valve replacement (AVR). Regional differences in ECV were measured between mid-ventricular and basal planes. To investigate their impact on arrhythmia vulnerability, a computational biventricular model was developed from MRI data of the patient who presented the highest ECV difference between the planes in absence of a scar determined by late gadolinium enhancement (male 75y, post-AVR, ECV mid 25.5%, ECV base 31.3%, Figure A). The model was divided in two regions and extracellular conductivities (GE) were adjusted in each region as described previously (1), with additional GE reduction in the high ECV region representing increased interstitial fibrosis. This approach resulted in GE being 26.4% lower for ECV of 31.3% when compared to ECV of 25.5%. A model with uniform ECV of 25.5% was used as a control. Myocardial tissue was modelled with a cell radius of 16 micrometers, as reported in AS patients (2). The right ventricular apex was paced with S1=750 ms for 10 beats, followed by rapid pacing with different cycle lengths spanning the 20 ms window before the loss of stimulus capture to test arrhythmia inducibility. The simulations were repeated with an additional GE reduction by 30% and 60% in both regions to mimic conduction delays from diffuse fibrosis. Results Cardiac MRI showed significantly higher ECV in the basal plane of AS patients when compared to the mid-ventricular plane, both before and after AVR (Figure B), with the largest ECV found after AVR (mid-ventricular: p<0.0001; basal: p=0.0011). No sex-specific differences were found. Simulations in the model with patient-derived ECV showed slightly longer QRS and lower CV than the model with uniform ECV (Table). By contrast, myocardial fibrosis had a larger impact on CV slowing. Arrhythmia was inducible when either diffuse fibrosis was present or ECV at the ventricular base was increased (Table). Conclusion Regional differences in ECV were found in the ventricles of AS patients. Computer simulations suggest that these differences have a minimal effect on ventricular conduction when compared to diffuse fibrosis. However, they might increase arrhythmia vulnerability even in the absence of diffuse fibrosis. Additional studies are necessary to investigate the effects of each on arrhythmia maintenance and cardiac mechanics.

Performance Enhancement of Indoor Cellular Visible Light Communication through Cell Size and Wavelength Reuse Pattern

The emerging technology of visible light communication (VLC) has become a promising solution for the requirements of wide-bandwidth, high-speed, and infinite-capacity wireless communication networks. A novel design of high-performance multi-user indoor visible light communication (VLC) based on hexagonal-cell arrangement is introduced in the present paper. The wavelength division multiple access (WDMA) is used to enable multiple users to communicate through the network of access point (APs) by assigning a unique wavelength division channel (WDC) to each user. A wavelength reuse scheme is utilized to increase the maximum number of users in the system and to enhance the VLC system capacity. The on–off keying (OOK) is used as the modulation technique for light signaling. The intercell interference (ICI) caused by the wavelength reuse is evaluated and its dependence on the cell radius and the wavelength reuse pattern size is numerically investigated. Both the received power density and the ICI at the location of the moving user are evaluated and the resulting signal-to-ICI ratio (SICIR) is calculated at every point over the indoor area. The VLC system capacity is evaluated and its dependence on the design parameters including the cell radius, the size of the wavelength reuse pattern, and the user data rate is numerically investigated. A design procedure is proposed to minimize the bit-error rate (BER) resulting from the ICI and to maximize the system capacity and the maximum allowable number of users in the system by selecting the optimal radius of the hexagonal cells and the most appropriate size of the frequency reuse pattern. The effect of the data rate per user on the system capacity is numerically investigated. It is shown that a SICR of greater than 21 dB and BER of less than 1 × 10−15 is achieved. Also, a system capacity of more than 4 bps/Hz is achieved by the application of the proposed VLC design optimization procedure.

Molecular Imaging with Aquaporin-Based Reporter Genes: Quantitative Considerations from Monte Carlo Diffusion Simulations.

Aquaporins provide a unique approach for imaging genetic activity in deep tissues by increasing the rate of cellular water diffusion, which generates a magnetic resonance contrast. However, distinguishing aquaporin signals from the tissue background is challenging because water diffusion is influenced by structural factors, such as cell size and packing density. Here, we developed a Monte Carlo model to analyze how cell radius and intracellular volume fraction quantitatively affect aquaporin signals. We demonstrated that a differential imaging approach based on subtracting signals at two diffusion times can improve specificity by unambiguously isolating aquaporin signals from the tissue background. We further used Monte Carlo simulations to analyze the connection between diffusivity and the percentage of cells engineered to express aquaporin and established a mapping that accurately determined the volume fraction of aquaporin-expressing cells in mixed populations. The quantitative framework developed in this study will enable a broad range of applications in biomedical synthetic biology, requiring the use of aquaporins to noninvasively monitor the location and function of genetically engineered devices in live animals.

Influence of cell specific parameters in a dielectric spectroscopy conversion model used to monitor viable cell density in bioreactors.

In the biopharmaceutical industry, the use of mammalian cells to produce therapeutic proteins is becoming increasingly widespread. Monitoring of these cultures via different analysis techniques is essential to ensure a good quality product while respecting good manufacturing practice (GMP) regulations. PAT (Process Analytical Technologies) tools provide real-time measurements of the physiological state of the culture and enable process automation. Dielectric spectroscopy is a PAT that can be used to monitor the viable cell concentration of living cells (VCC) after processing raw permittivity data. Several modeling approaches exist and estimate biomass with different accuracy. The accuracy of the Cole-Cole and Maxwell Wagner's equations are studied here in the determination of the VCC and cell radius in Chinese hamster ovary (CHO) culture. A sensitivity analysis performed on the parameters entering the equations highlighted the importance of the cell specific parameters such as internal conductivity (σi ) and membrane capacitance (Cm ) in the accuracy of the estimation of VCC and cell radius. The most accurate optimization method found to improve the accuracy involves in-process adjustments of Cm and σi in the model equations with samplings from the bioreactor. This combination of offline and in situ data improved the estimation precision of the viable cell concentration by 69% compared to a purely mechanistic model without offline adjustments. This article is protected by copyright. All rights reserved.

A three-dimensional compression-torsion metamaterial based on the three-period minimum surface theory

This paper proposes a novel design for a three-dimensional compression-torsion mechanical metamaterial based on the three-period minimal surface (TPMS) theory. Unlike the conventional approach of utilizing chiral or diagonal rod structures to achieve compressive-torsional properties in metamaterials, this paper employs a two-dimensional level of TPMS theory and the synergistic effect of a re-entrant structure to achieve compressive-torsional properties. Theoretical, experimental, and numerical methods were employed to investigate the deformation characteristics and mechanical properties of the proposed structure. The paper investigates the impact of the periodic value of the TPMS on the torsion direction, as well as the influence of unit cell radius r on the deformation characteristics, torsion angle, and Poisson's ratio of the lattice structure. The length of radius r can be appropriately selected to control the torsion angle and negative Poisson's ratio (NPR) effect of the structure. Furthermore, by adjusting the period values of the TPMS, the torsion direction of the structure can be controlled. Finally, the torsion angle, Poisson's ratio, stiffness and specific energy absorption (SEA) were compared with the structure with a diagonal rod microstructure (SDRM). The findings indicate that the proposed structure exhibits superior torsion performance and NPR effect compared to the previously proposed three-dimensional compression-torsion material. This design concept has significant implications for the development of smart devices, aerospace engineering, and conservation engineering applications.

Calculation of the DNA damage yield and relative biological effectiveness in boron neutron capture therapy via the Monte Carlo track structure simulation.

Objective.Boron neutron capture therapy (BNCT) is an advanced cellular-level hadron therapy that has exhibited remarkable therapeutic efficacy in the treatment of locally invasive malignancies. Despite its clinical success, the intricate nature of relative biological effectiveness (RBE) and mechanisms responsible for DNA damage remains elusive. This work aims to quantify the RBE of compound particles (i.e. alpha and lithium) in BNCT based on the calculation of DNA damage yields via the Monte Carlo track structure (MCTS) simulation.Approach. The TOPAS-nBio toolkit was employed to conduct MCTS simulations. The calculations encompassed four steps: determination of the angle and energy spectra on the nuclear membrane, quantification of the database containing DNA damage yields for ions with specific angle and energy, accumulation of the database and spectra to obtain the DNA damage yields of compound particles, and calculation of the RBE by comparison yields of double-strand break (DSB) with the reference gamma-ray. Furthermore, the impact of cell size and microscopic boron distribution was thoroughly discussed.Main results. The DSB yields induced by compound particles in three types of spherical cells (radius equal to 10, 8, and 6μm) were found to be 13.28, 17.34, 22.15 Gy Gbp-1for boronophenylalanine (BPA), and 1.07, 3.45, 8.32 Gy Gbp-1for sodium borocaptate (BSH). The corresponding DSB-based RBE values were determined to be 1.90, 2.48, 3.16 for BPA and 0.15, 0.49, 1.19 for BSH. The calculated DSB-based RBE showed agreement with experimentally values of compound biological effectiveness for melanoma and gliosarcoma. Besides, the DNA damage yield and DSB-based RBE value exhibited an increasing trend as the cell radius decreased. The impact of the boron concentration ratio on RBE diminished once the drug enrichment surpasses a certain threshold.Significance. This work is potential to provide valuable guidance for accurate biological-weighted dose evaluation in BNCT.

Schlesinger Nailed It! Assessing a Key Primary Pharmacodynamic Property of Phages for Phage Therapy: Virion Encounter Rates with Motionless Bacterial Targets.

Bacteriophages (phages) are viruses of bacteria and have been used as antibacterial agents now for over one-hundred years. The primary pharmacodynamics of therapeutic phages can be summed up as follows: phages at a certain concentration can reach bacteria at a certain rate, attach to bacteria that display appropriate receptors on their surfaces, infect, and (ideally) kill those now-adsorbed bacteria. Here, I consider the rate at which phages reach bacteria, during what can be dubbed as an 'extracellular search'. This search is driven by diffusion and can be described by what is known as the phage adsorption rate constant. That constant in turn is thought to be derivable from knowledge of bacterial size, virion diffusion rates, and the likelihood of phage adsorption given this diffusion-driven encounter with a bacterium. Here, I consider only the role of bacterial size in encounter rates. In 1932, Schlesinger hypothesized that bacterial size can be described as a function of cell radius (, or ), as based on the non-phage-based theorizing of Smoluchowski (1917). The surface area of a cell-what is actually encountered-varies however instead as a function . Here, I both provide and review evidence indicating that Schlesinger's assertion seems to have been correct.

Intelligent Resource Allocation in Backscatter-NOMA Networks: A Soft Actor Critic Framework

With the use of power domain non-orthogonal multiple access (NOMA) and backscatter communication (BAC), future sixth-generation ultra massive machine-type communications networks are expected to connect large-scale internet of things (IoT) devices. However, due to NOMA co-channel interference, the power allocation to large-scale IoT devices becomes critical. The existing convex optimization-based solutions are highly complex, and therefore it is difficult to find the optimal solution to the resource allocation problem in a highly dynamic environment. To alleviate this problem, this work develops an efficient model-free BAC approach with a NOMA system to assist the base station with complex resource scheduling tasks in a dynamic BAC-NOMA IoT network. The objective is to increase the sum rate of uplink backscatter devices. More specifically, we jointly optimize the transmit power of downlink IoT users and the reflection coefficient of uplink backscatter devices using a reinforcement learning algorithm, namely, the soft-actor critic (SAC) algorithm. With the advantage of entropy regularization, the SAC agent learns to explore and exploit the dynamic BAC-NOMA network efficiently. The proposed algorithm ensures the quality of service (QoS) requirements of downlink users while enhancing the sum rate of uplink backscatter devices. Numerical results reveal the superiority of the proposed algorithm over the conventional optimization (benchmark) approach in terms of the average sum rate of uplink backscatter devices. We show that the network with multiple downlink users obtained a higher reward with respect to a large number of iterations compared to episodes with a lower number of iterations. Moreover, the proposed algorithm outperforms the benchmark scheme and BAC with orthogonal multiple access in terms of the average sum rate with the different number of backscatter devices. Additionally, we show that our proposed algorithm enhances sum rate efficiency with respect to different self-interference coefficients and different noise levels. Finally, we evaluate and show the sum rate efficiency of the proposed algorithm with different QoS requirements and cell radii.

Intercellular mechanical signalling in a 3D nonlinear fibrous network model

The extracellular matrix (ECM) consists of a network of polymeric fibres in which cells are embedded and interact with each other. The nonlinear elasticity of the ECM aids in directing the transmission of cell-induced mechanical loads over long distances, thereby facilitating mechanical communication between cells that are not in direct contact. Previous computational models have established the role of compression-buckling of the ECM fibres in increasing the propagation range of mechanical loads and fibre remodelling, however, most of them are two-dimensional (2D). Here, we generate a more realistic, 3D finite-element simulation of two cells contracting within the ECM by means of two contractile spheres embedded within a network of beam elements. We explore the effects of the mechanical behaviour of the fibres (linear-elastic, compression-bucklable), network connectivity (3.7, 8, 12) and intercellular distance (1–5 cell radii) on the structural remodelling and mechanical loads occurring on the cell surface and within the intercellular region of the ECM. When cells were embedded in a matrix of bucklable rather than linear-elastic fibres, contraction-induced loads were more directed towards the neighbouring cell, and the fibre rearrangement in the intercellular ECM was more eminent up to an intercellular distance of ∼2.5–5 cell radii. Our 3D discrete model highlights the role of the ECM nonlinear elasticity in the efficient transfer of mechanical signals between cells, a mechanism governing numerous multicellular processes such as tissue morphogenesis, wound healing, angiogenesis and cancer metastasis. The findings reemphasise the importance of using nonlinear elastic gels in in vitro cellular models.

Mathematical model for force and energy of virion-cell interactions during full engulfment in HIV: Impact of virion maturation and host cell morphology.

Viral endocytosis involves elastic cell deformation, driven by chemical adhesion energy, and depends on physical interactions between the virion and cell membrane. These interactions are not easy to quantify experimentally. Hence, this study aimed to develop a mathematical model of the interactions of HIV particles with host cells and explore the effects of mechanical and morphological parameters during full virion engulfment. The invagination force and engulfment energy were described as viscoelastic and linear-elastic functions of radius and elastic modulus of virion and cell, ligand-receptor energy density and engulfment depth. The influence of changes in the virion-cell contact geometry representing different immune cells and ultrastructural membrane features and the decrease in virion radius and shedding of gp120 proteins during maturation on invagination force and engulfment energy was investigated. A low invagination force and high ligand-receptor energy are associated with high virion entry ability. The required invagination force was the same for immune cells of different sizes but lower for a local convex geometry of the cell membrane at the virion length scale. This suggests that localized membrane features of immune cells play a role in viral entry ability. The available engulfment energy decreased during virion maturation, indicating the involvement of additional biological or biochemical changes in viral entry. The developed mathematical model offers potential for the mechanobiological assessment of the invagination of enveloped viruses towards improving the prevention and treatment of viral infections.