Cellular Array Research Articles

A Biologically-Motivated Synchronization Problem in Cellular Automata

We study a biologically-motivated synchronization problem that gives a finite-state protocol for synchronizing cellular automata. The synchronization in cellular automata has been known as firing squad synchronization problem since its development, in which it was originally proposed by J. Myhill in the book edited by Moore [1964] to synchronize all/some parts of self-reproducing cellular automata. The problem has been studied extensively for more than fifty years. It is defined as follows: given a one-dimensional array of n identical cellular automata, including a general at one end that is activated at time t = 0 , we want to design the automata such that, at some future time , all the cells will simultaneously and, for the first time , enter a special firing state. The problem has been referred to as achieving a macro-synchronization in micro-synchronization system and realizing a global synchronization using only local information exchange. In this paper, we present a survey on recent developments in designing optimum- and non-optimum-time synchronization algorithms and their implementations for one- and two-dimensional cellular arrays. Several simple, state-efficient mapping schemes are proposed for embedding one-dimensional firing squad synchronization algorithms onto two-dimensional arrays. The discussions are made from a viewpoint of biological systems, including fault-tolerance, self-replication, self-reproduction, self-repairing and growing nature-based systems. [1] E. F. Moore: The firing squad synchronization problem. in Sequential Machines, Selected Papers, E. F. Moore, ed., Addison-Wesley, Reading MA.,(1964), pp. 213-214. [2] H. Umeo: Firing squad synchronization problem in cellular automata. In Encyclopedia of Complexity and System Science , R. A. Meyers (Ed.), Springer, Vol.4(2009), pp.3537-3574.

Characterization of Polyphenols from Lycium ruthenicum Fruit by UPLC-Q-TOF/MS(E) and Their Antioxidant Activity in Caco-2 Cells.

The fruit of Lycium ruthenicum Murr. (LRF) has long been used in folk medicine. Nevertheless, detailed information related to its polyphenol compositions remains scarce. In this study, we confirmed that the total phenolic and anthocyanin contents of LRF fruit extracts (LRFEs) were 4906.5 ± 60.6 mg of gallic acid equivalents/100 g DW and 787.6 ± 34.1 mg of cyanindin-3-glucoside equivalents/100 g DW, respectively. A characterization of LRFEs was performed by ultrahigh performance liquid chromatography/quadrupole time-of-flight mass spectrometry using an MS(E) data acquisition. A total of 26 polyphenols were tentatively identified, of which 19 represent the first reports of these polyphenols in LRFEs. Furthermore, the cellular antioxidant array showed that LRFEs could protect Caco-2 cells against H2O2-induced oxidative damage based on microscopic fluorometric imaging.

Input-driven languages are linear conjunctive

Linear conjunctive grammars define the same family of languages as one-way real-time cellular automata (A. Okhotin, “On the equivalence of linear conjunctive grammars to trellis automata”, RAIRO ITA, 2004), and this family is known to be incomparable with the context-free languages (V. Terrier, “On real-time one-way cellular array”, Theoret. Comput. Sci., 1995). This paper demonstrates the containment of the languages accepted by input-driven pushdown automata (a.k.a. visibly pushdown automata) in the family of linear conjunctive languages, which is established by a direct simulation of an input-driven automaton by a one-way real-time cellular automaton. On the other hand, it is shown that the language families defined by the unambiguous grammars, the LR(k) grammars and the LL(k) grammars are incomparable with the linear conjunctive languages.

Dynamically reconfigurable evolutionary multi-context robust cellular array design

This paper presents a novel dynamically reconfigurable evolutionary design of multi-context multi-output near real-time functions for implementation using a 2D cellular array structure. A genetic algorithm generates solutions that reuse the cells in the cellular array to implement multiple multi-output functions, thereby minimising the area overhead and power consumed. Further constraints are introduced to yield solutions that are resilient to single cell failure. Test vectors to identify the faulty cell are presented. The experimental validation and results of the proposed approach is demonstrated on a 5 × 5 cellular array to implement context-specific arithmetic functions under fault-free and faulty cell scenarios. The upper and lower bounds for the total time delay in the reconfigurable 2D array is derived.

A Multi-Modality CMOS Sensor Array for Cell-Based Assay and Drug Screening.

In this paper, we present a fully integrated multi-modality CMOS cellular sensor array with four sensing modalities to characterize different cell physiological responses, including extracellular voltage recording, cellular impedance mapping, optical detection with shadow imaging and bioluminescence sensing, and thermal monitoring. The sensor array consists of nine parallel pixel groups and nine corresponding signal conditioning blocks. Each pixel group comprises one temperature sensor and 16 tri-modality sensor pixels, while each tri-modality sensor pixel can be independently configured for extracellular voltage recording, cellular impedance measurement (voltage excitation/current sensing), and optical detection. This sensor array supports multi-modality cellular sensing at the pixel level, which enables holistic cell characterization and joint-modality physiological monitoring on the same cellular sample with a pixel resolution of 80 μm × 100 μm. Comprehensive biological experiments with different living cell samples demonstrate the functionality and benefit of the proposed multi-modality sensing in cell-based assay and drug screening.

PTPS-02FOXR2: AN ONCOGENE IN MEDULLOBLASTOMA

Medulloblastoma is the most common malignant brain tumor in children. There continues to be significant morbidity associated with current therapy, which includes surgery, chemotherapy and radiation. More knowledge about drivers of this tumor will allow development of more targeted therapies. Our lab has previously identified FOXR2 as a driver for MB using Sleeping Beauty insertional mutagenesis. We have begun to examine the role of FOXR2 in the role of medulloblastoma formation by over expression and transcription activator like effector nuclease mediated knock-out in cellular models, RNA sequencing and reverse phase protein array (RPPA) of these cells, and allograft mouse models. Overexpression of FOXR2 in a non-tumor forming, immortalized mouse cerebellar cell line (C17.2) results in significantly increased soft agar colony formation but no differences in proliferation. This is similar to the Koso et al, 2014 findings that examined the effects of FOXR2 overexpression in granule neuron progenitor cells. RNA sequencing of the C17.2 cells with foxr2 overexpression have identified upstream regulators which are activated such as HIF1A, IFG1, TP53, ERRB and MYC that have previously been identified to be upregulated in medulloblastoma. The exact mechanism of FOXR2 has yet to be elucidated and additional RNA sequencing of the knock out cell lines in comparison to the wild type will be conducted to further our understanding. RPPA has also been completed and analysis is being carried out currently. In addition to our in vitro findings we have examined the level of expression of 45 human medulloblastoma samples via staining of tissue microarray and from those samples there appears to be a subset of patients in the SHH subgroup which express FOXR2 at high levels. Our findings support that FOXR2 is an oncogene in a number of patients with SHH subtype medulloblastoma and may be a target for development of therapeutic targets.

Application of the pMHC Array to Characterise Tumour Antigen Specific T Cell Populations in Leukaemia Patients at Disease Diagnosis.

Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms’ Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8–1.4 x 106). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1126-134 (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1950-958 epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients.

Oscillatory cellular patterns in three-dimensional directional solidification.

We present a phase-field study of oscillatory breathing modes observed during the solidification of three-dimensional cellular arrays in microgravity. Directional solidification experiments conducted onboard the International Space Station have allowed us to observe spatially extended homogeneous arrays of cells and dendrites while minimizing the amount of gravity-induced convection in the liquid. In situ observations of transparent alloys have revealed the existence, over a narrow range of control parameters, of oscillations in cellular arrays with a period ranging from about 25 to 125 min. Cellular patterns are spatially disordered, and the oscillations of individual cells are spatiotemporally uncorrelated at long distance. However, in regions displaying short-range spatial ordering, groups of cells can synchronize into oscillatory breathing modes. Quantitative phase-field simulations show that the oscillatory behavior of cells in this regime is linked to a stability limit of the spacing in hexagonal cellular array structures. For relatively high cellular front undercooling (i.e., low growth velocity or high thermal gradient), a gap appears in the otherwise continuous range of stable array spacings. Close to this gap, a sustained oscillatory regime appears with a period that compares quantitatively well with experiment. For control parameters where this gap exists, oscillations typically occur for spacings at the edge of the gap. However, after a change of growth conditions, oscillations can also occur for nearby values of control parameters where this gap just closes and a continuous range of spacings exists. In addition, sustained oscillations at to the opening of this stable gap exhibit a slow periodic modulation of the phase-shift among cells with a slower period of several hours. While long-range coherence of breathing modes can be achieved in simulations for a perfect spatial arrangement of cells as initial condition, global disorder is observed in both three-dimensional experiments and simulations from realistic noisy initial conditions. In the latter case, erratic tip-splitting events promoted by large-amplitude oscillations contribute to maintaining the long-range array disorder, unlike in thin-sample experiments where long-range coherence of oscillations is experimentally observable.

Removable damping treatments for use in sheet metal fabrication

Many industrial fabrication processes on metallic structures generate a great deal of work place noise. For example, riveting and chiseling on light-weight, stiff aerospace structures such as fusalage components and flight surfaces subject the workpiece to repeated impacts and consequent noise generation. Many such structures may be lightly damped. Many damping treatments are targeted toward permanent installation on a structure, but if the treatments are considered to be removable, one has design freedoms including placement on a structure, as well as mass and damping means, that might not otherwise exist if the treatment had to remain in place. A shot-mass or particle-impact damper configured in an elastic, cellular array is shown to provide high loss factors and mass loading, which, along with ease of placement and removal, may provide significant reduction in component vibration during fabrication and consequent reduction in noise in the work place. The concept applied to an example aircraft panel when subjected to riveting operations yields more than 10 dB of noise reduction.

Panmictic and Clonal Evolution on a Single Patchy Resource Produces Polymorphic Foraging Guilds.

We develop a stochastic, agent-based model to study how genetic traits and experiential changes in the state of agents and available resources influence individuals’ foraging and movement behaviors. These behaviors are manifest as decisions on when to stay and exploit a current resource patch or move to a particular neighboring patch, based on information of the resource qualities of the patches and the anticipated level of intraspecific competition within patches. We use a genetic algorithm approach and an individual’s biomass as a fitness surrogate to explore the foraging strategy diversity of evolving guilds under clonal versus hermaphroditic sexual reproduction. We first present the resource exploitation processes, movement on cellular arrays, and genetic algorithm components of the model. We then discuss their implementation on the Nova software platform. This platform seamlessly combines the dynamical systems modeling of consumer-resource interactions with agent-based modeling of individuals moving over a landscapes, using an architecture that lays transparent the following four hierarchical simulation levels: 1.) within-patch consumer-resource dynamics, 2.) within-generation movement and competition mitigation processes, 3.) across-generation evolutionary processes, and 4.) multiple runs to generate the statistics needed for comparative analyses. The focus of our analysis is on the question of how the biomass production efficiency and the diversity of guilds of foraging strategy types, exploiting resources over a patchy landscape, evolve under clonal versus random hermaphroditic sexual reproduction. Our results indicate greater biomass production efficiency under clonal reproduction only at higher population densities, and demonstrate that polymorphisms evolve and are maintained under random mating systems. The latter result questions the notion that some type of associative mating structure is needed to maintain genetic polymorphisms among individuals exploiting a common patchy resource on an otherwise spatially homogeneous landscape.

Development of configurations for lookup table–based Embryonics using graphic mapping: A case study

This article presents the development of configurations for bio-inspired self-healing cellular arrays known as Embryonics (embryonic electronics). In the Embryonics design, the configurations are employed to define the functionality and connections of each cell. However, developing configurations of the Embryonics is a time-consuming and challenging work due to lack of effective tools. In this article, an approach is proposed to develop configurations using graphic mapping, which also optimizes the length of configurations for the Embryonics. Using metric embedding, the problem of configurations is exactly formulated to binary quadratic assignment problem and routing problem with constraint of the Embryonics architecture. Since binary quadratic assignment problem is nondeterministic polynomial-time hard, a genetic algorithm is used to tackle this problem for achieving high-quality placement. Due to the limitation of communication bandwidth, how to resolve congestion is also an important issue. An improved ant colony algorithm is presented to realize routing of the Embryonics based on the result of placement. Configurations of the Embryonics are formed according to the result of placement and routing. Experimental result on a [Formula: see text] multiplier demonstrates that developing configurations for lookup table–based Embryonics using graphic mapping can lower the difficulty of the Embryonics design and optimize placement and routing of Embryonics.

Effect of Core Geometry on Shear Moduli in Cellular Core Sandwich Structures

Cellular structures are lightweight structures with appropriate stiffness properties. Usually these cells are in the form of a honeycomb but various cell geometries can be considered as well, for special applications. Because of the repetitive nature of the cellular array the core can be considered as a homogeneous but anisotropic medium. In present study by changing in the number and positions of nodes, the number of cell walls and changing in size of RVE (Representative Volume Element), and also using homogenization method, the shear components of the elasticity tensor are obtained for heterogeneous geometries by assuming unconstraint core. The results show that the effect of these changes in geometry, increase the quality of shear stiffness and weight reduction for some core geometries of sandwich panels that have not been evaluated yet. Soar effect of rearrangement of walls and their located for transverse shear applications is the main characteristic of present study that results obtained have confirmed these claims. Advantage of the present study is providing new pattern applied for sandwich panels core those shear properties that have higher priority..

Trigger-Wave Asynchronous Cellular Logic Array for Fast Binary Image Processing

This paper presents the design and the VLSI implementation of an asynchronous cellular logic array for fast binary image processing. The proposed processor array employs trigger-wave propagation and collision detection mechanisms for binary image skeletonization, and Voronoi tessellation. Low power, low area, and high processing speed are achieved using full custom dynamic logic design. The prototype array consisting of 64 $\times$ 96 cells is fabricated in a standard 90 nm CMOS technology. The experimental results confirm the fast operation of the array, capable of extracting up to $2.78\times 10^{6}$ skeletons per second, consuming less than 1 nJ/skeleton. The asynchronous operation enables circular wave contours, which improves the quality of the extracted skeletons. The proposed asynchronous processing module consists of 24 MOS transistors and occupies $5.5 \mu{\rm m}\times 7.4 \mu{\rm m}$ area. Such array can be used as a co-processing unit aiding global binary image processing in standard pixel-parallel SIMD architectures in vision chips.

Integrated simulation of active carbon nanotube forest growth and mechanical compression

Carbon nanotube (CNT) forests are CNT populations that self-assemble into vertically oriented cellular arrays during growth. The anisotropic and inhomogeneous morphology of forests arises from complex mechanical interactions between CNTs during their collective growth and influences many forest properties. A time-resolved simulation is developed to model actively growing CNT populations having distributed properties and growth characteristics. The model considers van der Waals (vdW) attraction between neighboring CNTs and allows the growing and deforming CNTs to interact and react based on a balance of forces. Parametric variations of growth rate distribution and CNT occupation density generate variable CNT forest morphology in manners consistent with experimental observations. The forces opposing vdW bonding between contacting CNTs during forest growth are found to diminish with distance from the growth substrate and are proportional to CNT bending stiffness. Axial and transverse compression of simulated forests capture experimentally observed phenomena of coordinated axial buckling, transverse densification, and the foam-like force–displacement response that is typical of CNT forests. This new paradigm in CNT forest modeling may be used as an analytical tool to examine CNT forest growth kinetics, multi-physics CNT forest performance, and the post-synthesis processing and forming of CNT forest microstructures.

Concise Review: Modeling Multiple Sclerosis With Stem Cell Biological Platforms: Toward Functional Validation of Cellular and Molecular Phenotypes in Inflammation-Induced Neurodegeneration

In recent years, tremendous progress has been made in identifying novel mechanisms and new medications that regulate immune cell function in multiple sclerosis (MS). However, a significant unmet need is the identification of the mechanisms underlying neurodegeneration, because patients continue to manifest brain atrophy and disability despite current therapies. Neural and mesenchymal stem cells have received considerable attention as therapeutic candidates to ameliorate the disease in preclinical and phase I clinical trials. More recently, progress in somatic cell reprogramming and induced pluripotent stem cell technology has allowed the generation of human "diseased" neurons in a patient-specific setting and has provided a unique biological tool that can be used to understand the cellular and molecular mechanisms of neurodegeneration. In the present review, we discuss the application and challenges of these technologies, including the generation of neurons, oligodendrocytes, and oligodendrocyte progenitor cells (OPCs) from patients and novel stem cell and OPC cellular arrays, in the discovery of new mechanistic insights and the future development of MS reparative therapies.

Magnetic thin-film insulator with ultra-low spin wave damping for coherent nanomagnonics.

Wave control in the solid state has opened new avenues in modern information technology. Surface-acoustic-wave-based devices are found as mass market products in 100 millions of cellular phones. Spin waves (magnons) would offer a boost in today's data handling and security implementations, i.e., image processing and speech recognition. However, nanomagnonic devices realized so far suffer from the relatively short damping length in the metallic ferromagnets amounting to a few 10 micrometers typically. Here we demonstrate that nm-thick YIG films overcome the damping chasm. Using a conventional coplanar waveguide we excite a large series of short-wavelength spin waves (SWs). From the data we estimate a macroscopic of damping length of about 600 micrometers. The intrinsic damping parameter suggests even a record value about 1 mm allowing for magnonics-based nanotechnology with ultra-low damping. In addition, SWs at large wave vector are found to exhibit the non-reciprocal properties relevant for new concepts in nanoscale SW-based logics. We expect our results to provide the basis for coherent data processing with SWs at GHz rates and in large arrays of cellular magnetic arrays, thereby boosting the envisioned image processing and speech recognition.

Microfluidics-based laser cell-micropatterning system

The ability to place individual cells into an engineered microenvironment in a cell-culture model is critical for the study of in vivo relevant cell–cell and cell–extracellular matrix interactions. Microfluidics provides a high-throughput modality to inject various cell types into a microenvironment. Laser guided systems provide the high spatial and temporal resolution necessary for single-cell micropatterning. Combining these two techniques, the authors designed, constructed, tested and evaluated (1) a novel removable microfluidics-based cell-delivery biochip and (2) a combined system that uses the novel biochip coupled with a laser guided cell-micropatterning system to place individual cells into both two-dimensional (2D) and three-dimensional (3D) arrays. Cell-suspensions of chick forebrain neurons and glial cells were loaded into their respective inlet reservoirs and traversed the microfluidic channels until reaching the outlet ports. Individual cells were trapped and guided from the outlet of a microfluidic channel to a target site on the cell-culture substrate. At the target site, 2D and 3D pattern arrays were constructed with micron-level accuracy. Single-cell manipulation was accomplished at a rate of 150 μm s−1 in the radial plane and 50 μm s−1 in the axial direction of the laser beam. Results demonstrated that a single-cell can typically be patterned in 20–30 s, and that highly accurate and reproducible cellular arrays and systems can be achieved through coupling the microfluidics-based cell-delivery biochip with the laser guided system.

A class of time-optimum FSSP algorithms for multi-dimensional cellular arrays

The firing squad synchronization problem (FSSP) on cellular automata has been studied extensively for more than fifty years, and a rich variety of synchronization algorithms has been proposed not only for one-dimensional arrays but also for two-dimensional arrays. In the present paper, we propose a new class of time-optimum FSSP algorithms for multi-dimensional cellular arrays. The algorithm is based on a simple recursive-halving marking schema and it can synchronize any two-dimensional (2D) rectangular arrays of size m×n with a general at one corner in m+n+max(m,n)-3 optimum-steps. The algorithm is a natural expansion of the well-known one-dimensional (1D) FSSP algorithms proposed by Balzer (1967), Gerken (1987), and Waksman (1966) and it can be easily expanded to three-dimensional (3D) arrays, even to multi-dimensional arrays. The algorithm proposed is isotropic concerning the side-lengths of multi-dimensional arrays and this isotropic property yields algorithmic correctness and easy verification for the multi-dimensional time-optimum FSSP algorithms designed.

Research on the Design Method of Self-Repairing Digital Integrated Circuit Based on Embryonic Cellular Array

A digital circuit with self-repairing characteristic based on embryonic cellular array, which attempts to draw inspiration from the biological process of ontogeny, to implement novel digital computing machines endowed with better hardware fault-tolerant capabilities is researched in this paper. The Self-repairing Digital Circuit (SDC) consists of the two-dimensional electronic cellular array, the SDC's structure and the self-repairing mechanism are expounded, and the design of the cellular circuit based on LUT (look-up table) is proposed. Then, a multiplication circuit is presented as an example of the application of the SDC, the function and self-repairing ability of the multiplication circuit by SDC are demonstrated by the simulation results.

Inflatable shape changing colonies assembling versatile smart space structures

Various plants have the ability to follow the sun with their flowers or leaves during the course of a day via a mechanism known as heliotropism. This mechanism is characterised by the introduction of pressure gradients between neighbouring motor cells in the plant׳s stem, enabling the stem to bend. By adapting this bio-inspired mechanism to mechanical systems, a new class of smart structures can be created. The developed overall structure is made up of a number of cellular colonies, each consisting of a central pressure source surrounded by multiple cells. After launch, the cellular arrays are deployed in space and are either preassembled or alternatively are attached together during their release or afterwards. A central pressure source is provided by a high-pressure storage unit with an integrated valve, which provides ingress gas flow to the system; the gas is then routed through the system via a sequence of valve operations and cellular actuations, allowing for any desired shape to be achieved within the constraints of the deployed array geometry. This smart structure consists of a three dimensional adaptable cellular array with fluid controlling Micro Electromechanical Systems (MEMS) components enabling the structure to change its global shape. The proposed MEMS components include microvalves, pressure sensors, mechanical interconnect structures, and electrical routing. This paper will also give an overview of the system architecture and shows the feasibility and shape changing capabilities of the proposed design with multibody dynamic simulations. Example applications of this lightweight shape changing structure include concentrators, mirrors, and communications antennas that are able to dynamically change their focal point, as well as substructures for solar sails that are capable of steering through solar winds by altering the sails׳ subjected area.