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Tumor-infiltrating immune cells (TIICs) have become an important source of markers for predicting the clinical outcomes of cancer patients. However, measurements of cellular heterogeneity vary due to the frequently updated reference genomes and gene annotations. In this study, we systematically collected and evaluated the infiltration pattern of 65 immune cells. We constructed the Immune Cell Pair (ICP) score based on the cell pair algorithm in 3,715 samples and across 12 independent cancer types, among which, the ICP score from six cancer types was further validated in 2,228 GEO samples. An extensive tumorigenic and immunogenomic analysis was subsequently conducted. As a result, the ICP score showed a robust reliability and efficacy in predicting the survival of patients with gliomas, in pan-cancer samples, and six independent cancer types. Notably, the ICP score was correlated with the genomic alteration features in gliomas. Moreover, the ICP score exhibited a remarkable association with multiple immunomodulators that could potentially mediate immune escape. Finally, the ICP score predicted immunotherapeutic responses with a high sensitivity, allowing a useful tool for predicting the overall survival and guiding immunotherapy for cancer patients.

Contact inhibition of locomotion (CIL), in which cells repolarize and move away from contact, is now established as a fundamental driving force in development, repair, and disease biology. Much of what we know of CIL stems from studies on two-dimensional (2D) substrates that do not provide an essential biophysical cue—the curvature of extracellular matrix fibers. We discover rules controlling outcomes of cell–cell collisions on suspended nanofibers and show them to be profoundly different from the stereotyped CIL behavior on 2D substrates. Two approaching cells attached to a single fiber do not repolarize upon contact but rather usually migrate past one another. Fiber geometry modulates this behavior; when cells attach to two fibers, reducing their freedom to reorient, only one cell repolarizes on contact, leading to the cell pair migrating as a single unit. CIL outcomes also change when one cell has recently divided and moves with high speed—cells more frequently walk past each other. Our computational model of CIL in fiber geometries reproduces the core qualitative results of the experiments robustly to model parameters. Our model shows that the increased speed of postdivision cells may be sufficient to explain their increased walk-past rate. We also identify cell–cell adhesion as a key mediator of collision outcomes. Our results suggest that characterizing cell–cell interactions on flat substrates, channels, or micropatterns is not sufficient to predict interactions in a matrix—the geometry of the fiber can generate entirely new behaviors.

Whilst reverse electrodialysis (RED) has been extensively characterised for saline gradient energy from seawater/river water (0.5 M/0.02 M), less is known about RED stack design for high concentration salinity gradients (4 M/0.02 M), important to closed loop applications (e.g. thermal-to-electrical, energy storage). This study therefore focuses on the scale-up of RED stacks for high concentration salinity gradients. Higher velocities were required to attain a maximum Open Circuit Voltage (OCV) for 4 M/0.02 M, which gives a measure of the electrochemical potential of the cell. The experimental OCV was also much below the theoretical OCV, due to the greater boundary layer resistance observed, which is distinct from 0.5 M/0.02 M. However, negative net power density (net produced electrical power divided by total membrane area) was demonstrated with 0.5 M/0.02 M for larger stacks using shorter residence times (three stack sizes tested: 10 × 10cm, 10 × 20cm and 10 × 40cm). In contrast, the highest net power density was observed at the shortest residence time for the 4 M/0.02 M concentration gradient, as the increased ionic flux compensated for the pressure drop. Whilst comparable net power densities were determined for the 10 × 10cm and 10 × 40cm stacks using the 4 M/0.02 M concentration gradient, the osmotic and ionic transport mechanisms are distinct. Increasing cell pair number improved maximum current density. This subsequently increased power density, due to the reduction in boundary layer resistance, and may therefore be used to improve thermodynamic efficiency and power density from RED for high concentrations. Although comparable power densities may be achieved for small and large stacks, large stacks maybe preferred for high concentration salinity gradients due to the comparative benefit in thermodynamic efficiency in single pass. The greater current achieved by large stacks may also be complemented by an increase in cell pair number and current density optimisation to increase power density and reduce exergy losses., Graphical abstract Image 1, Highlights • RED for energy generation from high concentration salinity gradients in studied. • Boundary layer effects require higher velocities to achieve maximum OCV. • Highest power at short residence time with larger stack contrasting sea/riverwater. • Same power density for small and large stacks, but higher current in large stack. • More cell pairs lowers boundary layer resistance and improves power density.

A defect-based bridge fault represents the faulty behavior of an interconnect short defect obtained by SPICE-simulating the two shorted cells with the short defect injected. In this paper, we have developed a framework to automatically extract defect-based bridge faults and utilize commercial ATPG to generate corresponding test patterns for a given design. Defect-based bridge fault model can not only describe the faulty behavior of a short defect precisely but also result in collapsible faults at one shorted cell pair. As a result, using defect-based bridge fault model for ATPG can lead to a significantly smaller bridge-fault test set when compared to conventional 4-way dominance bridge fault model, where four non-collapsible faults at one shorted cell pair are considered for ATPG. Also, some short defects can only be detected by the test set for defect-based bridge faults but not by the test set for 4-way dominance bridge faults with more test patterns. The experimental result based on industrial designs has demonstrated the effectiveness of using defect-based bridge faults for ATPG while showing an affordable runtime on extracting defect-based bridge faults.

Variations in functional parameters strongly affect the performance of the electrodialysis process, a promising approach for desalinating brackish water. Although the effects of operational factors have been qualitatively investigated in previously published works, the simultaneous effects of three important operational factors, applied voltage, superficial velocity, and temperature, have not yet been quantitatively described or presented in the form of a mathematical model. Therefore, the simultaneous effects of these operational parameters have not been shown in functional form in the previously published works. In this research, a laboratory-scale electrodialysis setup was used to qualitatively and quantitatively study the effects of operational factors by employing a set of full-factorial experiments with three replications at different levels of applied voltage per cell pair, superficial velocity, temperature, and feedwater composition. The nonlinear power-law functions were found for the effects of superficial velocity, applied voltage per cell pair, and initial feed concentration, while an Arrhenius-type function was found for the effect of temperature.

Engineered nanomaterials (ENMs) are increasingly used in consumer products due to their unique physicochemical properties, but the specific hazards they pose to the structural and functional integrity of endothelial barriers remain elusive. When assessing the effects of ENMs on vascular barrier function, endothelial cell monolayers are commonly used as in vitro models. Monolayer models, however, do not offer a granular understanding of how the structure–function relationships between endothelial cells and tissues are disrupted due to ENM exposure. To address this issue, we developed a micropatterned endothelial cell pair model to quantitatively evaluate the effects of 10 ENMs (8 metal/metal oxides and 2 organic ENMs) on multiple cellular parameters and determine how these parameters correlate to changes in vascular barrier function. This minimalistic approach showed concerted changes in endothelial cell morphology, intercellular junction formation, and cytoskeletal organization due to ENM exposure, which were then quantified and compared to unexposed pairs using a “similarity scoring” method. Using the cell pair model, this study revealed dose-dependent changes in actin organization and adherens junction formation following exposure to representative ENMs (Ag, TiO2 and cellulose nanocrystals), which exhibited trends that correlate with changes in tissue permeability measured using an endothelial monolayer assay. Together, these results demonstrate that we can quantitatively evaluate changes in endothelial architecture emergent from nucleo-cytoskeletal network remodeling using micropatterned cell pairs. The endothelial pair model therefore presents potential applicability as a standardized assay for systematically screening ENMs and other test agents for their cellular-level structural effects on vascular barriers.

Pairs of corresponding cytotoxic drug sensitive and resistant cell lines are powerful tools to develop treatment strategies. Developing cytotoxic drug resistant cell lines is a well-established method in cancer research. In more than fifty years of sulfur mustard (SM) resistant research such a cell pair has never been produced. Hereinafter we describe the first successful approach to develop a SM resistant keratinocyte cell line. Starting with the SM sensitive keratinocyte cell line HaCaT we used a strategy of continuous exposure with gradually increased concentrations. Cells were cultured in total for more than 40 months starting with an initial concentration of 0.07 μM SM twice a week up to a final concentration of 7.2 μM SM. The achieved cell line HaCaT/SM had an LC50 resistance increase of 4.7-fold and an LC90 increase of 8.2-fold. Hereinafter we demonstrate the production of the first sulfur mustard (SM) resistant cell line. The new achieved cell line called HaCaT/SM is able to tolerate a continuous exposure of an SM concentration, which is associated with an inhibitory effect of 93% within the original HaCaT cells, which were used as starting point.

Electrodialysis has been used for treating toxic substances such as heavy metals and minimizing secondary environmental pollution problems effectively. However, electrodialysis depends on the operating parameters as well as fluid dynamics and electrical properties. This study provides design elements for the treatment of heavy metal-containing wastewater by electrodialysis. We found that the limiting current density (LCD) is proportional but not completely linear to the diluate concentration over a threshold value. In contrast, it is linear to the linear flow velocity for the whole range. As the number of cell pairs increases, because linear flow velocity and LCD increase, the removal efficiency of heavy metals also increases. Therefore, for highly concentrated wastewater, increasing the linear flow velocity, the applied voltage, and the number of cell pairs can effectively improve removal efficiency. It was found that the current efficiency is as low as 17% when the removal efficiency of heavy metals exceeds 95%. Thus, it is necessary to select an operating range that optimizes the operating and initial investment costs for the effective removal of heavy metals using electrodialysis.

Automated tracking of cells in time-lapse live-imaging datasets of developing multicellular tissues is gaining popularity in developmental biology for understanding the cell growth dynamics. The tracking of plant cells across noisy microscopy image sequences is very challenging, because plant cells in noisy region cannot be correctly segmented and cause serious errors in subsequent cell tracking procedure. In this paper, we present to track plant cells across noisy images using a tracking method which is based on Faster R-CNN and dynamic local graph matching. Faster R-CNN is employed to detect cells in noisy images, and it is improved by cell characteristic prior bounding box design and soft non-maximum suppression strategies. Then a dynamic local graph matching model is proposed to track the detected plant cells, by exploiting the cells’ tight spatial and temporal contextual information. It tends to prevent the cell matching error accumulation by selecting the most similar cell pair in the dynamically growing neighbor set of matched cells. Compared with the existing tracking methods for plant cells, the experimental results show that the proposed method can greatly improve the tracking accuracy.

Early embryonic cell cycles usually progress with S and M phases without any gap phase. How the gap phases are introduced spatiotemporally over development remains poorly defined. To establish the cell-specific introduction of gap phases in embryo, we generate multiple fluorescence ubiquitin cell cycle indicators (FUCCI) in C. elegans. Time-lapse 3D imaging followed by lineal expression profiling reveals sharp and differential dynamics of the FUCCI reporters, allowing the precise demarcation of cell cycle phases throughout embryogenesis. Surprisingly, most cells divide with S and M phase only until they have completed their last round of division, after which they arrest in the G0 or G1 phase with two exceptions. Only a single cell pair divides with full cycle and the E2 and E4 cells temporarily acquire the G2 phase. In summary, we provide a first global picture of gap phase introduction in a metazoan embryo with the newly developed FUCCI reporters.

High purity ultrapure water is required in the electronics and pharmaceutical industries. Herein, we report production of high purity ultrapure water (18.5 L/h) by electrodeionization (EDI) technique in a laboratory scale EDI unit (effective membrane area 24 cm × 6 cm) using polyethylene interpolymer based ion-exchange membranes. The ultrapure water also prepared by EDI process in the same EDI unit using two different types of commercial membranes (Ionsep and Fujifilm type II). The resistance of ultrapure water was 18.2 MΩ cm with the interpolymer based membranes at 25 V/cell pair applied potential, whereas with commercial Ionsep and Fujifilm type II membranes the final resistance of ultrapure water was 15 MΩ cm and 17.1 MΩ cm respectively at 30 V/cell pair applied potential. The power consumption (W) and current efficiency (CE) values were 0.324 KWhkg–1 and 58.86% respectively for interpolymer based ion-exchange membranes, whereas for Ionsep and Fujifilm type II membranes, W and CE values were 0.658 and ...

Microbial desalination cells (MDCs) are being developed as a low-energy desalination technology. Most MDCs in the previous studies contained one cell pair (CP, a pair of cation and anion exchange membranes) and very few had multiple CPs (

Analysis of surface textures of physiographic features extracted from multiscale digital elevation models via grey level co-occurrence matrix This paper is aimed at employing grey level co-occurrence matrix (GLCM) to analyse the surface textures of physiographic features extracted from multiscale digital elevation models (DEMs). Four GLCM parameters, energy, contrast, autocorrelation and entropy, are computed for horizontal (0°), vertical (90°) and diagonal (45 and 135°) cell pair orientations. For the respective DEMs and physiographic features, varying patterns are observed in the plots of the GLCM parameters due to varying surface profiles and the changes that occur over the scales. Due to the smoothing of the terrain during multiscaling, the features have increasing values of energy and entropy, and decreasing values of contrast and entropy, indicating decreasing roughness. Mountains have the highest roughness as compared to the other features over the scales, while basins have the lowest roughness. For each parameter, similar trends are observed in the plots for the four different cell pair orientations, indicating similar trends of change of surface texture in the different orientations over the scales. However, varying values are observed for the different orientations, depending on textural uniformity in the corresponding orientations. The results obtained demonstrate that GLCM can be an appropriate tool for classifying landforms from multiscale DEMs based on the different texture characteristics of the landforms.

The application of bipolar electrodialysis (BPED) for the simultaneous removal of inhibitory acetate and pH control during E. coli fermentation was investigated. A two cell pair electrodialysis module, consisting of cation exchange, anion exchange and bipolar membranes with working area of 100 cm(2) each, was integrated with a standard 7 l stirred tank bioreactor. Results showed that BPED was beneficial in terms of in situ removal of inhibitory acetate and a reduction in the amount NH(4)OH used for pH control. In batch and fed-batch BPED fermentations, base additions were decreased by up to 50% in both cases compared to electrodialysis (ED) fermentations with pH controlled at 6.7 +/- 0.1. Consequently, the final biomass (34.2 g DCW l(-1)) and recombinant protein (5.5 g l(-1)) concentrations obtained were increased by up to 37 and 20%, respectively.

Plants from the genus Vernonia produce a variety of flavonoids and bitter sesquiterpene lactones important for agriculture and human health. Leaf glandular trichomes of Vernonia galamensis ssp. galamensis var. ethiopica Gilbert (VGAE) were investigated for ultrastructural development and content composition because sesquiterpene lactones that impart a bitter taste to the leaves have been associated with the presence of these glands. Trichome ultrastructure was examined using LM, SEM, and TEM. Glands were removed from the leaf surface, and the chemical composition of gland contents was determined using HPLC and high‐resolution mass spectrometry. Immature and mature 10‐celled peltate biseriate glandular trichomes were present only at the abaxial side of the leaf. A large subcuticular space (head) developed from the most distal cell pair of the mature trichome and gradually filled with an osmiophillic substance. Mass spectrometry analysis revealed that the peltate trichome is a major source of prevernocistif...

In most tissues of vertebrates, gap junctions control the exchange of ions and small molecules between adjacent cells, thus co-ordinating the cellular activities. The application of the dual voltage-clamp method to cell pair preparations enables one to elucidate the electrical properties of gap junctions and gap junction channels. The conductive and kinetic data obtained at the multichannel and single channel level led to a generalised concept for the operation of gap junction channels. Based on the biological data gained in this way, a mathematical model has been developed. This model is versatile and allows to simulate the electrophysiological behaviour of different types of vertebrate gap junctions.

Mathematical modeling of the electric activity of pairs of true (central) and latent (peripheral) sinoatrial pacemaker cells coupled through gap junctions revealed that attenuation of coupling conductance increases the beat phase shift; below a critical conductance there is no synchronization. The phase difference also depends on the type of interacting cells, being maximal for a “central”-“peripheral” cell pair.

Mobility Robustness Optimization (MRO) is a use-case of Self-Organizing Networks (SON) for LTE that aims to optimize handover performance automatically. Conventional MRO algorithms tune handover parameters based on counts of handover failures and handover events. The algorithm requires many handovers per cell pair (e.g. 1000) to trigger a reliable adjustment. Thus it can result in a slow adaptation to changes that improve or deteriorate handover performance, such as network loading or UE speed. In this paper, we propose a new MRO algorithm taking into account soft metrics, such as handover command transmission time, derived both from failed and successful handovers. The proposed algorithm provides a faster reaction and lower failure rate than the conventional method, with no deterioration in the handover count.

The crisp organization of the "firing bumps" of entorhinal grid cells and conjunctive cells leads to the notion that the entorhinal cortex may compute linear navigation routes. Specifically, we propose a process, termed "linear look-ahead," by which a stationary animal could compute a series of locations in the direction it is facing. We speculate that this computation could be achieved through learned patterns of connection strengths among entorhinal neurons. This paper has three sections. First, we describe the minimal grid cell properties that will be built into our network. Specifically, the network relies on "rigid modules" of neurons, where all members have identical grid scale and orientation, but differ in spatial phase. Additionally, these neurons must be densely interconnected with synapses that are modifiable early in the animal's life. Second, we investigate whether plasticity during short bouts of locomotion could induce patterns of connections amongst grid cells or conjunctive cells. Finally, we run a simulation to test whether the learned connection patterns can exhibit linear look-ahead. Our results are straightforward. A simulated 30-min walk produces weak strengthening of synapses between grid cells that do not support linear look-ahead. Similar training in a conjunctive cell module produces a small subset of very strong connections between cells. These strong pairs have three properties: the pre- and post-synaptic cells have similar heading direction. The cell pairs have neighboring grid bumps. Finally, the spatial offset of firing bumps of the cell pair is in the direction of the common heading preference. Such a module can produce strong and accurate linear look-ahead starting in any location and extending in any direction. We speculate that this process may: (1) compute linear paths to goals; (2) update grid cell firing during navigation; and (3) stabilize the rigid modules of grid cells and conjunctive cells.

A key enabler for the construction of large-scale intelligent surveillance systems is the accurate estimation of activity topology graphs. An activity topology graph describes the relationships between the fields of view of the cameras in a surveillance network. An accurate activity topology estimate allows higher-level processing such as network-wide tracking to be localised within neighbourhoods defined by the topology, and thus to scale. The camera overlap graph is an important special case of the general activity topology, in which edges represent overlap between cameras’ fields of view. We describe a family of pairwise occupancy overlap estimators, which are the only approaches proven to scale to networks with thousands of cameras. A distributed implementation is described, which enables the estimator to scale beyond the limits achievable by centralised implementations, and supports growth of the network whilst it remains online. Formulae are derived to describe the memory and network bandwidth requirements of the distributed implementation, which are verified by empirical results. Finally, the efficacy of the overlap estimators is demonstrated using results from their application in higher-level processing, specifically to network-wide tracking, which becomes feasible within the topology oriented architecture.

The repeating unit consisting of a cell pair of one concentrate and one feed compartment of an electropermutation stack is modeled. Both the feed and the concentrate compartments are filled with an ...

Early after depolarizations (EADs) induce triggered activity in Purkinje (P) fibers that can initiate ventricular (V) arrhythmias. However, it is unclear whether PV interactions suppress or induce EAD formation at the discrete Purkinje-ventricular junctions (PVJs). Using a PV cell pair approach based on the Tan and Joyner coupling circuit, we determined the extent to which EADs initiated in P myocytes were suppressed by coupling to V cells. Our results suggest that PV interactions tend to suppress EAD formation at the PVJ except under pathological conditions (e.g., infarction) in which the V mass is severely reduced.

In the normal heart, most of the individual cardiac cells are well coupled to adjacent cells through gap junctions. Because of this, the myocardium is referred to as an electrical syncytium such that excitation occurring at any location is able to spread throughout all parts of the heart which are not refractory to stimulation. The process of action potential propagation in the heart has generally been considered as a multi-dimensional analog of the continuous one-dimensional propagation observed in unmyelinated nerve fibers.

In Hydra vulgaris at the level of dissociated single cells endodermal cells adhere to each other more readily than to ectodermal cells at the initial adhesion. The time required for adhesion to occur between two adjacent cells is shorter for both endodermal and ectodermal homotypic cell adhesions once the initial adhesion of the first pair of cells has been established. It is confirmed that contact of an aggregated pair with additional homotypic cells facilitates the occurrence of homotypic adhesions; heterotypic adhesions are discouraged. This suggests that adhesion of homotypic cells contributes to an increased readiness for subsequent homotypic cells to adhere.

The idea that the junctional conductance might be modulated was verified in the 1970’s (1, 2). It is known since Engelmann (3) that "the death of a cardiac cell does not result in the death of the apposing cells" ("der Tod schreitet nicht von Zelle auf Zelle for"). This important conclusion was based on the observation that the injury potential induced by lesion of cardiac muscle soon vanishes (healing-over) — a phenomenon that was not related to the depolarization of the surface cell membrane because a new lesion applied near the previous one re-established the injury potential (8).

Cell pairs isolated from adult rat and guinea pig ventricles were used to study the transfer of action potentials from cell to cell and to assess the electrical properties of cardiac gap junctions. An attempt was made to correlate the impulse transfer with the conductance of the gap junction membrane and the number of operational gap junction channels.