A compact computational model for cell construct development in perfusion culture

Compact Modeling of Physical Mechanisms Present in the Weak Breakdown Regime of Advanced Si and SiGe Bipolar Transistors

The analytical modeling of nanoscale devices is an important area of computer-aided design for fast and accurate nanoelectronic design and optimization. In the present paper, a new approach for modeling semiconductor devices, nanoscale double gate DG MOSFETs, by use of the gradual channel approximation (GC) approach and genetic algorithm optimization technique (GA) is presented. The proposed approach combines the universal optimization and fitting capability of GA and the cost-effective optimization concept of quantum correction, to achieve reliable, accurate and simple compact models for nanoelectronic circuit simulations. Our compact models give good predictions of the quantum capacitance, threshold voltage shift, quantum inversion charge density and drain current. These models have been verified with 2D self-consistent results from numerical calculations of the coupled Poisson-Schrödinger equations. The developed models can also be incorporated into nanoelectronic circuit simulators to study the nanoscale CMOS-based devices without impact on the computational time and data storage.

In this paper, we amalgamate three-layer hypothesis of compact star models given by Ginzburg (Usp Fiz Nauk 103:393, 1971) with our recent works on core-envelope compact star models (Gedela et al. in Eur Phys J C 79:566, 2019; Pant et al. in Eur Phys J C 79:602, 2019) and propose a three-layered relativistic stellar model endowed with distinct equation of states (EoSs) in the realm of general relativity. Instead of considering core and envelope of a neutron star, we insert an extra layer, namely, an intermediate layer in between the core and envelope to enhance a new conceptual aspect of realistic and accurate modeling of internal structure of stellar objects. The quark core is assumed to satisfy MIT-bag EoS, an intermediate region and a thin envelope of matter are considered with modified Bose–Einstein condensate (BEC) and quadratic EoSs, respectively. Further, respective pairs of interfaces in between stellar objects are matched with Dormois–Israel conditions. We verify almost all physical and geometrical parameters, including anisotropic, radial pressure, compactification factor, energy conditions, and stability conditions using TOV equation are with viable trends and continuous with the smooth variations throughout interior of the stars.

Compact models of semiconductor devices play a crucial role in design and analysis of large circuits. This paper presents a qualitative study of diode compact models including temperature dependency and reverse recovery phenomenon. The comprehensive behaviour of p-n junction diode is captured using Verilog-A language which is compatible to standard SPICE simulators. In this work, three types of diode models have been investigated based on temperature scale. Similar to SPICE compact models, a set of tuneable parameters are defined and presented for each type. In addition, an extensive study of reverse recovery has been done to determine the magnitude of reverse current and to evaluate model parameters like charge storage time and transition time based on input switching and temperature. Simulation results show that the developed model in this work is compatible like standard compact model scalable with area, temperature and intrinsic carrier concentration.

A single nucleotide polymorphism (SNP) identified between caveolin-1 (CAV1) and caveolin-2 (CAV2) on chromosome 7 is associated with glaucoma. One function of CAVs is endocytosis and recycling of extracellular matrix (ECM) components. Here, we generated CAV-silencing lentivirus to evaluate the effects on ECM turnover by trabecular meshwork (TM) cells and to measure the effect on outflow facility in anterior segment perfusion culture. Short hairpin CAV1 and CAV2 silencing and control lentivirus were generated, characterized, and applied to anterior segments in perfusion culture. Colocalization of CAVs with various ECM molecules in TM cells was investigated using immunofluorescence and confocal microscopy. Western immunoblotting and fluorogenic-based enzyme activity assays were used to investigate ECM protein levels and degradation, respectively. Endogenous CAVs colocalized with cortactin at podosome- or invadopodia-like structures (PILS), which are areas of focal ECM degradation. In perfusion culture, outflow rates increased significantly in CAV1-silenced anterior segments, whereas outflow significantly decreased in CAV2-silenced anterior segments. Matrix metalloproteinase (MMP)2 and MMP14, and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4) colocalized with both CAVs in TM cells. Protein levels and enzyme activities of MMP/ADAMTS4, fibronectin protein levels, actin stress fibers, and α-smooth muscle actin were all increased in CAV-silenced cells. Caveolin-mediated endocytosis is one mechanism by which TM cells can alter the physiological catabolism of ECM in order to change the composition of the outflow channels in the TM to regulate aqueous outflow resistance. Dysregulation of CAV function could contribute to the pathological changes in ECM that are observed in glaucoma.

Three-layer viscoelastic model with eddy viscosity effect for flexural-gravity wave propagation through ice cover

Single Event Transient (SET) is an important issue concerning reliability of MOS devices. Lots of experimental and simulation works have already been done [1- 4] but few of them are dealing with compact modelling. In this paper, we develop a physical model which describes the transient current pulse which appears at the electrodes of a Bulk MOSFET after the striking of an ionizing particle in the device. The validation of the model has been done by some confrontations with TCAD simulations. It turned out that the developed model has an innovative aspect for implementation into SPICE simulator.

A compact model is proposed to derive the charge density of the AlInSb/InSb HEMT devices by considering the variation of Fermi level, the first subband, the second subband and sheet carrier charge density with applied gate voltage. The proposed model considers the Fermi level dependence of charge density and vice versa. The analytical results generated by the proposed model are compared and they agree well with the experimental results. The developed model can be used to implement a physics based compact model for an InSb HEMT device in SPICE applications.

For the development of a perfusion culture producing recombinant human protein C, the effects of fetal calf serum and growth factors on cell growth and recombinant protein production were investigated. Although the growth of recombinant cells was stimulated by serum in a dose-dependent manner, a lower concentration of serum (2%) could support both synthesis and post-translational modification of protein C as efficiently as 10% serum. Among the growth factors tested, transferrin enhanced protein C production to the level comparable with 10% serum, while insulin was effective in maintaining cellular metabolism. Based on these results, a perfusion culture for a scale-up production of recombinant protein C was done using an Opticell culture system. A good productivity of the recombinant protein was obtained in low serum or serum-free medium for more than one month.

Bioreactor culture duration of engineered constructs influences bone formation by mesenchymal stem cells.

The continuous increase in the urban population worldwide has exacerbated the intensity of urban land use conversion and spatial consumption. This motivation for a better urban space led to the evolution of sustainable urban development, urban liveability, environmental awareness, inclusivity, and urban governance. Therefore, this research aimed to establish the intricate links between sustainable urban development, urban liveability, and inclusive physical development in selected cities in North-Central Nigeria. The theories examined were Citizen Participation, Dependency, Modernisation, and Infrastructure. The selected cities were Lokoja, Lafia, and Minna, all incidentally equidistant to Abuja, the Federal Capital City of Nigeria. This research employed a mixed-methods approach by collecting both qualitative and quantitative data. These data sets ranged from satellite imageries used for the spatio-temporal analysis and urban growth simulation through ArcGIS, Q-GIS, and the Artificial Neural Network. The extent of infrastructure provision and their methods were appraised using the instrumentality of the nearest neighbour analysis and the partial least square analysis using the SmartPLS. The research also appraised the stakeholders’ perceptions and methods of infrastructure provision through a word cloud analysis using NVivo analytics. In analysing the provision and condition of the infrastructure in North-Central Nigeria, educational infrastructure was found to be inadequate and poorly maintained; inadequate budgetary allocations exacerbated the problem of urban infrastructure overuse; illegal developments often overtook sites reserved for infrastructure; and funding, vandalism, and project continuity were cited as critical factors. The infrastructure that suffered the highest maintenance neglect was the urban water supply, education infrastructure, and the health care facilities. Political motivation and the population played the most significant roles in the region's urban infrastructure or project development. The triad of consumption, access, and equity was used to evaluate Hangwurian City Development's (HCD) proposed sustainable urban infrastructure development plan. Convergent validity was strong in the region, where the AVE was significant at 0.56 or more. A compact development model was found to be a valuable indicator for qualifying the cities. It was found that the challenge of planning regulation and siting of infrastructure could be addressed effectively, however, the public and private sector promoters of projects had to stick to their parts of the bargain. Cities across North-Central Nigeria had to undertake citizen-focused infrastructure planning and development. Therefore, the researcher concluded that city development and urban growth could be moderated through the instrumentality of adequate infrastructure provision and planning to prioritise the needs and desires of residents. This is achievable by adopting the Hangwurian City Development Model, which helps to promote cities without ills.

Background: The tumor microenvironment (TME) is a 3D, dynamic interaction between tumor and stromal cells, extracellular matrix, and soluble factors which can promote tumor progression and resistance to therapy. Significant efforts are being made to develop long-term in vitro TME models to study cancer biology, improve drug development, and guide clinical decisions. We have developed a cost-effective micro-bioreactor culture device which enables a wide variety of dynamic cellular and TME interactions that can be monitored with in situ, label free, and non-lytic microscopic analysis. Using the 3DKUBE™, we developed a 3D breast cancer model composed of MCF-7 cells and fibroblasts in segregated co-culture and identified a highly active PI3K inhibitor that had limited activity in 2D monoculture. Based on a more complex morphologic and functional 3D mammary gland model that incorporates multiple human primary cells including epithelial cells (HuMEC), mammary fibroblasts, and adipocytes, our long-term 3D perfused tri-culture breast cancer model is designed to evaluate drug response continuously using non-lytic analysis. We theorize that different breast cancer epithelial cells will be supported in a standard 3D stromal platform which supports mammary gland function. Herein, we describe the 3DKUBE™ modifications and early optimization of a defined stromal TME which supports HuMECs in 3D perfusion. Materials & Methods: Primary human cells were used to optimize seeding conditions for silk fibroin scaffolds containing Matrigel™/collagen hydrogels, including, media composition, cellular ratios, flow rates, and analytical methods for the 3DKUBE™. Destructive analytical methods included morphology (H&E), phenotype (histology), viability & survival (CyQuant, TUNEL, Ki-67), and ER, PR, and casein expression (RT-PCR). Non-lytic assays included metabolism (resazurin reduction), cytotoxicity (LDH release), soluble biomarker expression (xMAP™), and two-photon emission fluorescence via multiphoton microscopy (MPM). Results: The 3DKUBE™ imaging window (1.25 mm thick with a refractive index of 1.590, transmittance (~90%) at wavelengths >290 nm) was replaced with a No. 1.5 glass, high resolution window allowing non-destructive, in situ microscopic imaging. MPM images obtained provided cellular detail (granularity, nuclear-cytoplasmic ratio, size). Optimization of the media conditions and cell numbers revealed that a tri-culture ratio of 1:1:1 was stable in the silk-Matrigel-collagen scaffold during prolonged static and perfusion culture in mixed media. Differentiation of adipocytes had to be performed separately from the tri-culture due to the cytotoxicity of the differentiation media to the epithelial cells. This was achieved via a serial seeding and differentiation method. Our initial drug studies revealed that cytotoxicity could be monitored over the course of a week by multiple methods, including LDH secretion, Presto blue, and CyQuant. Though non-specific drug binding (CPT-11) was seen in the complex 3D matrix, it did not materially impact total drug concentrations. Conclusions: Our current optimization results indicate our ability to grow a bioengineered 3D human breast tri-culture model under perfusion using the 3DKUBE™ while monitoring tissue structure, function, and drug response through both lytic and non-lytic methods. Future Development: The optimized perfused stroma will be used to develop ex vivo breast microtumors of clinically relevant subtypes (ER+, Her+, triple negative) validated against targeted agents. If validated, these 3D microtumors may be applied as predictive phenotypic screens to improve preclinical and clinical breast cancer drug development. Citation Format: Teresa M. DesRochers, Stephen Shuford, Terri F. Bruce, Matthew R. Gevaert, Chaitra Cheluvaraju, Irene Georgakoudi, David L. Kaplan, Davie E. Orr, Howland E. Crosswell. Development of a perfusion-based 3D human tri-culture breast microtumor. [abstract]. In: Abstracts: AACR Special Conference on Cellular Heterogeneity in the Tumor Microenvironment; 2014 Feb 26-Mar 1; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(1 Suppl):Abstract nr A40. doi:10.1158/1538-7445.CHTME14-A40

Learning portable neural networks is very essential for computer vision for the purpose that pre-trained heavy deep models can be well applied on edge devices such as mobile phones and micro sensors. Most existing deep neural network compression and speed-up methods are very effective for training compact deep models, when we can directly access the training dataset. However, training data for the given deep network are often unavailable due to some practice problems (\eg privacy, legal issue, and transmission), and the architecture of the given network are also unknown except some interfaces. To this end, we propose a novel framework for training efficient deep neural networks by exploiting generative adversarial networks (GANs). To be specific, the pre-trained teacher networks are regarded as a fixed discriminator and the generator is utilized for derivating training samples which can obtain the maximum response on the discriminator. Then, an efficient network with smaller model size and computational complexity is trained using the generated data and the teacher network, simultaneously. Efficient student networks learned using the proposed Data-Free Learning (DFL) method achieve 92.22% and 74.47% accuracies without any training data on the CIFAR-10 and CIFAR-100 datasets, respectively. Meanwhile, our student network obtains an 80.56% accuracy on the CelebA benchmark.

Model-based movement patterns play a crucial role in evaluating the performance of mobility-dependent Personal Communication Service (PCS) strategies. This study proposes a new normal walk model to represent more closely the daily movement patterns of a mobile station (MS) in PCS networks than a conventional random walk model. The proposed walk model uses a drift angle θ to determine the direction in which an MS leaves a hexagonal cell in the next one step. The angle θ is assumed to approach the normal distribution with the parameters: μ = 0° and σ is on the interval [5°; 90°], based on the concept that most trips follow the shortest path, to make the movement patterns more realistic. A compact classification that types cells with side indices is further developed to partition an n-layer cluster of PCS networks into 12 mirror regions; consequently, the number of states can be reduced significantly, and the computational complexity is also reduced in the probability derivation. Two metrics are formulated in experiments to measure the expected and average numbers of steps taken by an MS to move out of an n-layer cluster. Experimental results confirm that for σ = 10°, 30°, 60°, and 90°, the discrepancies between the analytical computations and the simulated values are all within ±0.46%, and most are even within ±0.35%. Moreover, when σ is set to 71°, a normal walk can almost represent, and even replace, a conventional random walk, since the discrepancies between them are all within ±0.71%.

The performance evaluation of fatigue crack propagation is essential for the safe and stable operation of power plants. In this study, the Walker equation is employed, considering the loading ratio effect. The parameters in the Walker equation for AISI 304 L are fitted by a normal probability distribution based on the experimental information . A numerical simulation of the fatigue crack growth is carried out using the extended finite element method with the Walker equation embended in, and verified on a round compact tension model with the loading ratios of R = 0.1, 0.5, and 0.85. Finally, a fatigue crack growth simulation of a vertical centrifugal pump-turbine runner under turbine conditions is conducted with two crack positions. The crack morphology can be captured together with the corresponding fatigue life by using the developed fatigue crack propagation simulation method based on the extended finite element method. The numerical results can be used as guidance for improving the maintenance plan of pump plants.