2D Platform Research Articles

4168 Understanding ECM-Based Drug Resistivity in Breast Cancer

OBJECTIVES/GOALS: Cell-cell (CC) and cell-matrix interactions (CM) are known to affect drug sensitivity of cancer cells, but are not effectively recapitulated using 2D platforms. This research aims to determine how cell and matrix interactions confer drug resistivity in 3 distinct culturing models: 2D (no CM/limited CC), 3D spheroids (CC) and 3D fibronectin (both). METHODS/STUDY POPULATION: We examined four breast cancer cell types. The cells were derived from a nonmetastatic primary tumor (HMLE-E2) or overt bone-metastasis (BM). Transglutaminase 2 (TGM2), a matrix crosslinking protein, is overexpressed in metastatic bone tumors and may play a key role in matrix-conferred drug resistivity. In a gain-of-function model, TGM2 was upregulated in HMLE-E2 cells and compared to shTGM2 knockdown BM cells. Growth rates were analyzed using metabolic activity over 8 days, and drug sensitivity to Neratinib (0-1000 nM) was analyzed via cell titer. To account for the different transport properties of the 3 distinct culture environments, we developed a mathematical model for each condition, allowing us to normalize the drug sensitivity results across models to effectively compare true biological resistivity. RESULTS/ANTICIPATED RESULTS: We observed that increased cellular levels of TGM2 significantly increase the growth rate and drug resistivity of cells on fibronectin matrices. Interestingly, in 2D cultures, TGM2 expression was correlated with higher Neratinib resistivity but did not affect growth rates. In spheroid models without a significant matrix component, that rely solely on cell-cell junctions, high levels of TGM2 were correlated with lower survival rates. Lower levels of TGM2 are correlated with a more epithelial phenotype, and using our mathematical model we have identified significant transport differences between high and low TGM2 spheroids. We theorize that the low TGM2 spheroids have denser packing, which lowers the rate of diffusion and, thus reduces the effective concentration of the drug to the majority of the cells. DISCUSSION/SIGNIFICANCE OF IMPACT: Our studies indicate that the cellular response to drugs can be altered by changes in both transport properties of the tissue and the CM interactions. By systematically investigating the effects of CC interactions and CM interactions, we can use mathematical models to delineate physical means of drug resistivity from a biologically driven resistance.

Establishment of a primary cell culture of bone metastasis from urothelial carcinoma.

e17030 Background: Urothelial carcinoma (UC) accounts for 90% of cases of bladder cancer. In advanced UC diagnosis, skeletal involvement is frequent. Here we report the establishment of a primary culture of bone metastasis (BM) from High Grade UC derived from 81 years-old patient with a previous diagnosis of papillary urothelial cancer in 2016. After 2 years, patient relapsed to bone and visceral sites and because of poor clinical condition, patient underwent palliative best supportive care. Methods: Patient-derived bone metastatic cell culture was obtained from a surgical specimen. Tumor cells were isolated by collagenase digestion. Cells were seeded on in vitro 2D plates or into 3D collagen scaffolds composed of bovine collagen type I. The establishment of tumor cell isolation was confirmed through the evaluation of cytomorphologic features and positive pan-citokeratin staining. Then, drug treatments was performed and cell survival was evaluated. The study was approved by Ethical Committee and patient signed an informed consent. Results: After a long-term culture, we were able to isolate from a 3D scaffold a tumor clone that successfully growth until passage 20. Stabilized cells generate spheroid-like aggregates, recreating acinar-structures typical of the primary papillary urothelial tumor. Next, we treated cells with: Gemcitabine (Gem), Carboplatin (Carbo), Docetaxel, Carbo+Gem and Bone targeted drugs (Zoledronic Acid and Denosumab). The most effective treatment was Gem+Carbo, in particular 24% of survival in 2D platform and 87% on 3D collagen scaffold. For all treatments, cells cultured on 3D scaffold were more resistant to drugs, mimicking more closely the in-vivo condition. Conclusions: We were able to isolate and establish a BM primary culture from UC using a 3D in-vitro collagen scaffold. This system can recreate microenvironmental conditions more similar to in-vivo ones and it promoted the isolation of tumor cell clones from stromal components of the heterogeneous primary culture. This cell line could be useful to investigate the molecular and genetic profile in order to identify promising molecular targets and to better understard the natural history of BM from UC.

A scalable and xeno-free bioreactor system for biomanufacturing of hUC-MSCs

Background & Aim Mesenchymal stem/stromal cells (MSCs) are a prominent cell type in cellular therapies with over 900 registered clinical trials. A critical bottleneck in using MSCs, however, is generating the large number of cells required for both clinical trials and commercial therapies. Many commercial therapies will require 100’s of millions to billions of cells. While 2D cell culture may be able to generate sufficient cells for development and early clinical trials, later clinical trials and commercial therapies will require 3D bioreactors in a scalable manufacturing platform. Thus for consistency in the therapeutic product from the development stage through clinical trials and commercial therapies, it is necessary that the state of the cells be comparable across the transition from 2D to 3D culture and then maintained with scale-up in 3D. Here, we establish a scalable 3D manufacturing process using MSCs isolated from human umbilical cord tissue (hUC-MSCs) to generate cells at a consistent PDL that maintain comparable critical quality attributes (CQAs) to 2D flask culture. Methods, Results & Conclusion hUC-MSCs were isolated from the perivascular region of human umbilical cords. Using a xeno-free culture system (medium, reagents and materials), cells were cryopreserved to create a Working Cell Bank (WCB). WCB vials were expanded either in 2D cell stacks or on microcarriers in a small-scale (0.1L) or larger scale (15L) bioreactor. Cells were then assessed for CQAs: final PDL, typical MSC surface marker expression (positive for CD90 and CD166, negative for CD34 and CD45), trilineage differentiation potential (osteogenesis, adipogenesis, and chondrogenesis), and functional properties including IDO secretion and angiogenic cytokine secretion (VEGF, IL-8, bFGF, HGF, TIMP1 and TIMP2). hUC-MSCs were successfully expanded in 2D flasks, a 0.1L bioreactor, and a 15L bioreactor. Cells maintained all the tested CQAs across both 2D and 3D manufacturing platforms as well as with increases in scale in 3D. Therefore, this study establishes a scalable xeno-free manufacturing paradigm to reproducibly generate populations of hUC-MSCs that have consistent properties. Repeatedly generating cell populations with similar attributes is critical for well-designed studies during the development of cellular therapy approaches and as these approaches move towards clinical trials and commercial therapies.

Artificial Intelligence Based Game Levelling

The game development process is becoming a more detailed structure every day. The applications of artificial intelligence (AI), which is a comprehensive information technology, have been closely related to game technologies. In this study, the levelling process of a 2-dimensional (2D) platform game was investigated. The game developed and called “Renga” has a basic gameplay. Game data has been processed through an artificial neural network (ANN), k-nearest neighbour, decision and random tree algorithms and deep learning model that is trained with gameplay and user information. The classification process with the output data provides results for the next game level. In this way, the most effective playability impression that the developers offer to the game users has been created according to game. Furthermore, the variety of difficulty calculated with dynamic data by the user is provided by Renga, in which new sections/levels are created with user-specific assets. Thus, the most efficient gaming experience has been transferred to the users.

On-chip trans-dimensional plasmonic router

Abstract Plasmons, as emerging optical diffraction-unlimited information carriers, promise the high-capacity, high-speed, and integrated photonic chips. The on-chip precise manipulations of plasmon in an arbitrary platform, whether two-dimensional (2D) or one-dimensional (1D), appears demanding but non-trivial. Here, we proposed a meta-wall, consisting of specifically designed meta-atoms, that allows the high-efficiency transformation of propagating plasmon polaritons from 2D platforms to 1D plasmonic waveguides, forming the trans-dimensional plasmonic routers. The mechanism to compensate the momentum transformation in the router can be traced via a local dynamic phase gradient of the meta-atom and reciprocal lattice vector. To demonstrate such a scheme, a directional router based on phase-gradient meta-wall is designed to couple 2D SPP to a 1D plasmonic waveguide, while a unidirectional router based on grating metawall is designed to route 2D SPP to the arbitrarily desired direction along the 1D plasmonic waveguide by changing the incident angle of 2D SPP. The on-chip routers of trans-dimensional SPP demonstrated here provide a flexible tool to manipulate propagation of surface plasmon polaritons (SPPs) and may pave the way for designing integrated plasmonic network and devices.

Silver nanoparticles embedded on mesoporous-silica modified reduced graphene-oxide nanosheets for SERS detection of uremic toxins and parathyroid hormone

Silver nanoparticles (AgNPs) were successfully immobilized onto mesoporous silica (MPS)-modified reduced graphene oxide (mrGO) nanosheets to form AgNPs@mrGO surface-enhanced Raman scattering (SERS)-active substrates for bio-detection. Using the highly porous structure of MPS with the beneficial Raman enhancement of rGO nanosheets as templates, the homogeneous dispersion of AgNPs was self-assembled on a floating 2D platform of mrGO nanosheets. These were evaluated by transmission electron microscopy, X-ray diffraction, and UV–Vis spectroscopy. The pore-channels (~5 nm) of mrGO could be applied as templates to manipulate the interparticle gaps and particle size of AgNPs to obtain uniform nanoparticle arrays. Compared with AgNPs@mrGO and AgNPs@rGO (rGO substrate without MPS), the signal-to-background ratio (S/B ratio) was enhanced 6.9 times by mrGO addition. This indicates that the increase in SERS intensity and reduction in the background by using the template of the mrGO. AgNPs@mrGO SERS-active substrate can be exploited for rapid and sensitive detection of uremic toxins (creatinine, uric acid, and urea) and parathyroid hormone (PTH) for chronic kidney disease. The rapid, reproducible, and ultrasensitive detection of uremic toxins (<10−6 M of uric acid) and PTH (<0.2 ng/mL) could be achieved without labeling.

Embedded carbon nanowire in black phosphorene and C-doping: the rule to control electronic properties

Tuning the properties of black phosphorene such as structural, electronic and transport are explored via substitutional C-doping. We employed density functional theory calculations in combination with the non-equilibrium Green’s function for modeling the systems. Our results revealed that substitutional C-doped phosphorene is energetically favorable and ruled by the exothermic process. We also found that C-doping induces a change of the electric properties, such as a semiconductor-to-metal transition for the most lower concentration and zig-zag C-wire. Furthermore, for an armchair C-wire at the highest concentration, the semiconductor character is kept, meanwhile direct-to-indirect transitions are observed in the band gap nature. The band structures show that there exists a dependence of the electronic charge transport with the directional character of the C-doped configuration. The findings demonstrate that the directional doping could play a key role for the conductance of a 2D platform.

Hanoman adventure game based on Android

The use of smartphones to play mobile games is increasingly being used by everyone from children to adults. Along with the rapid development of the game industry, game engine software is now popping up, one of which is Construct 2. Construct 2 is an HTML5-based game maker software that is devoted to the 2D platform. Games can be a medium for cultural preservation in a country. One of them is Indonesian culture that needs to be preserved is wayang culture. This adventure game will raise a cultural puppet character named Hanoman, Hanoman is a figure in the form of a white monkey who acts as a character in helping Rama to save Shinta. This Hanoman adventure game in carrying out missions on each level will face the enemy characters who must be defeated to be able to open the next level. In this game, there are 3 levels where each level has different difficulties so that it can provide challenges for its users.

Recent Advances on Black Phosphorus Based Electrocatalysts for Water‐Splitting

AbstractHydrogen from electrocatalytic water splitting is a clean and renewable source of sustainable energy. Highly efficient electrocatalyst is of great importance for the low‐cost and large‐scale production of hydrogen. Effective electrocatalysts made of earth abundant elements such as element P have attracted extensive interest. Due to the attractive properties of black phosphorus (BP) including tunable physicochemical characteristics, unique in‐plane anisotropic structure, high charge‐carrier mobility, and large specific surface area, make it stand out from four allotropes. And the breakthrough in BP exfoliation enables it to be a promising 2D platform for designing flexible and versatile BP‐based materials. This review summarizes all these bulk BP, BP nanosheets, BP quantum dots (QDs) as well as BP‐based materials as efficient electrocatalysts in the last several years, with their synthesis methods and electrocatalytic properties for water splitting. Furthermore, some challenges and perspectives for the future development of BP‐based electrocatalysts have been briefly offered.

On Fundamental Principles for Thermal-Aware Design on Periodic Real-Time Multi-Core Systems

With the exponential rise of the transistor count in one chip, the thermal problem has become a pressing issue in computing system design. While there have been extensive methods and techniques published for design optimization with thermal awareness, there is a need for more rigorous and formal thermal analysis in designing real-time systems and applications that demand a strong exception guarantee. In this article, we analytically prove a series of fundamental properties and principles concerning the RC thermal model, peak temperature identification, and peak temperature reduction for periodic real-time systems, which are general enough to be applied on 2D and 3D multi-core platforms. These findings enhance the worst-case temperature predictability in runtime scenarios, as well as help to develop more effective thermal management policy, which is key to thermal-constrained periodic real-time system design.

Pulsed electromagnetic fields potentiate the paracrine function of mesenchymal stem cells for cartilage regeneration

BackgroundThe mesenchymal stem cell (MSC) secretome, via the combined actions of its plethora of biologically active factors, is capable of orchestrating the regenerative responses of numerous tissues by both eliciting and amplifying biological responses within recipient cells. MSCs are “environmentally responsive” to local micro-environmental cues and biophysical perturbations, influencing their differentiation as well as secretion of bioactive factors. We have previously shown that exposures of MSCs to pulsed electromagnetic fields (PEMFs) enhanced MSC chondrogenesis. Here, we investigate the influence of PEMF exposure over the paracrine activity of MSCs and its significance to cartilage regeneration.MethodsConditioned medium (CM) was generated from MSCs subjected to either 3D or 2D culturing platforms, with or without PEMF exposure. The paracrine effects of CM over chondrocytes and MSC chondrogenesis, migration and proliferation, as well as the inflammatory status and induced apoptosis in chondrocytes and MSCs was assessed.ResultsWe show that benefits of magnetic field stimulation over MSC-derived chondrogenesis can be partly ascribed to its ability to modulate the MSC secretome. MSCs cultured on either 2D or 3D platforms displayed distinct magnetic sensitivities, whereby MSCs grown in 2D or 3D platforms responded most favorably to PEMF exposure at 2 mT and 3 mT amplitudes, respectively. Ten minutes of PEMF exposure was sufficient to substantially augment the chondrogenic potential of MSC-derived CM generated from either platform. Furthermore, PEMF-induced CM was capable of enhancing the migration of chondrocytes and MSCs as well as mitigating cellular inflammation and apoptosis.ConclusionsThe findings reported here demonstrate that PEMF stimulation is capable of modulating the paracrine function of MSCs for the enhancement and re-establishment of cartilage regeneration in states of cellular stress. The PEMF-induced modulation of the MSC-derived paracrine function for directed biological responses in recipient cells or tissues has broad clinical and practical ramifications with high translational value across numerous clinical applications.

Unravelling the interfacial charge migration pathway at atomic level in 2D/2D interfacial Schottky heterojunction for visible-light-driven molecular oxygen activation

Visible-light-driven molecular oxygen activation (MOA) is deemed as the potential route to enhance oxidation capacity of molecular oxygen, while activation efficiency is significantly impeded thanks to the deficient charge carrier separation and transfer. In this work, an atomic scale 2D/2D Schottky heterojunction is prepared using titanium carbide as 2D platform for in situ growth of 2D ultrathin bismuth molybdate nanosheet through anaerobically hydrothermal conditions. This 2D/2D Schottky heterojunction displays high performance for MOA, which is 5.56-fold higher than pristine one. The excellent activation efficiency is originated from ultrahigh charge carrier transfer channel, in which the surface charge transfer efficiency is enhanced (30.73 % vs 18.45 %) and the surface recombination constant is decreased (0.0019 s−1 vs 0.0031 s−1) compared to pristine one. The mechanism of photocatalytic MOA is unearthed based on experiment results and various characterizations. This study shows the great potential of atomic scale 2D/2D Schottky heterojunction in photocatalytic MOA.

Galactose-Grafted 2D Nanosheets from the Self-Assembly of Amphiphilic Janus Dendrimers for the Capture and Agglutination of Escherichia coli.

High aspect ratio, sugar-decorated 2D nanosheets are ideal candidates for the capture and agglutination of bacteria. Herein, the design and synthesis of two carbohydrate-based Janus amphiphiles that spontaneously self-assemble into high aspect ratio 2D sheets are reported. The unique structural features of the sheets include the extremely high aspect ratio and dense display of galactose on the surface. These structural characteristics allow the sheet to act as a supramolecular 2D platform for the capture and agglutination of E. coli through specific multivalent noncovalent interactions, which significantly reduces the mobility of the bacteria and leads to the inhibition of their proliferation. Our results suggest that the design strategy demonstrated here can be applied as a general approach for the crafting of biomolecule-decorated 2D nanosheets, which can perform as 2D platforms for their interaction with specific targets.

Difficulty Adjustment Using Player's Performance and Electroencephalographic Data

For high skilled players, an easy game might become boring and for low skilled players, a difficult game might become frustrating. The purpose of this research was to create new and better ways to offer players with different skills, an appropriate experience. We focused on adapting the difficulty levels of a simple 2D platform game, designing and building levels automatically. The proposed method consists of Dynamic Difficulty Adjustment (DDA) and Rhythm-Group Theory (a procedural content generation method), combined with levels of attention obtained from Electroencephalographic (EEG) data. Experiments were designed in the way that players had to clear five different levels that were created automatically using the player's performance and EEG data obtained from a biosensor while playing. Results showed that the method successfully adapts the level difficulty according to the player's status. In addition, the designed method calculates difficulty using values computed in real time to decide the shape and structure of the levels. The method designed in this research can be implemented not only in platformers but also in other genres that involve elements of rhythm, additionally, it could be used by game developers as a tool for playtesting in order to improve the game design, receive quantitative and numerical feedback from players and create an overall better experience for their players.

Penerapan Algoritma Backpropagation Pada Game Pengenalan Nahwu Di Mi Darul Falah Jepara

Nahwu is a science that studies Arabic grammar. Nevertheless, the interest of students in learning nahwu is currently decreasing. It happens because the technological advancement vastly develops but the way of learning it is still conventional and tends to be boring. Based on the school data for the academic year of 2017/2018 at MI Darul Falah Sirahan Cluwak Pati, there were only 20 students able to undestand nahwu well out of 60 students who started learning nahwu in class IV. Technological development has brought many changes to things around us. One of the most developed at the meantime is game. Lately games have become something very fast developing. Using the game to be used as a secondary learning media for students in learning nahwu is considered quite effective. The method used in designing this game was Backpropagation meaning an algorithm based on artificial neural networks which is used to determine and take decision that is used to determine scores and levels in the Nahwu Introduction Game. The tools used in this game-making are construct 2, an HTML5-based game maker specifically for the 2d platform. The results of this study were an Android-based Nahwu Introduction Game.

Few-Layer PbI2 Nanoparticle: A 2D Semiconductor with Lateral Quantum Confinement.

Inspired by the superior optoelectronic performances of various 2D semiconductors, their new compositions and structures are being actively pursued in order to foster novel fundamental physics and device applications. As a layered semiconductor with a direct bandgap, few-layer PbI2 should have drawn much research attention due to their capability of emitting photons at short wavelengths of the visible spectrum. Here we chemically synthesize few-layer PbI2 flakes and nanoparticles, which demonstrate unique exciton properties that have rare counterparts in other 2D semiconductors. For three layers and more, the single PbI2 flakes can be utilized to show how the bandgap energy of a 2D semiconductor evolves with the changing layer thickness. The single PbI2 nanoparticles are associated with an ultranarrow photoluminescence line width of ∼1 meV, thus reflecting the influence of lateral quantum confinement on the energy-level structures of a 2D semiconductor. The above findings mark the emergence of a potent 2D platform that is more than complementary to well-studied transition-metal dichalcogenide monolayers.

PY-RATE ADVENTURES: A 2D Platform Serious Game for Learning the Basic Concepts of Programming With Python

Background. Learning programming is a cognitively demanding field of study accompanied with various difficulties. Although there is a high demand in the market for programmers, software analysts and engineers, a high dropout rate is recorded in relevant fields of study. Serious games are a promising means of engaging students in learning programming by giving them more incentives and making the process of learning programming concepts and languages more entertaining. Aim. This article introduces a new serious game called PY-RATE ADVENTURES, which aims to assist young students in their introduction to the basic programming concepts using Python. The game does not have any prerequisites and is suitable for players with no previous knowledge of programming. This article aims to present important information regarding the analysis, design and pilot evaluation of PY-RATE ADVENTURES. Method. The game was evaluated by 31 people that had recently graduated or were students of an Interdepartmental Programme of Postgraduate Studies in Information Systems. The participants voluntarily played the game and answered a questionnaire based on the MEEGA+ model, after their hands on experience with the game. This questionnaire’s purpose was to evaluate PY-RATE ADVENTURES in terms of perceived player experience and short-term learning. Results. The participants positively evaluated the game almost in all the elements of player experience. Furthermore, the majority of the users consider that the game helped them to learn basic programming concepts in Python and stated that they would prefer to learn programming with this game rather than other teaching methods. Conclusion. The positive results of the pilot evaluation give us the motivation to proceed and evaluate the game with students in secondary education, in order to extract stronger and generalisable conclusions regarding the impact of the game as an educational tool for learning programming concepts.

Application of the Finite State Machine Algorithm on 2D Platformer Rabbit Games vs Zombies

This research develops Android games by applying the FSM Algorithm (Finite State Machine) for the movement of NPC (Non-Player Character) to produce dynamic movements. The popular and legendary game with the appearance of side scroller is Super Mario Bross and Shovel Knight, the game is the most preferred game of its time to the present, but the game does not apply AI (Artificial Intelligence) so the game seems less challenging. The game is a concept game that is currently rarely used. Based on this, a side scroller-based survival game was created by implementing AI on NPCs on the Android platform. The AI used is the FSM Algorithm which functions to regulate enemy movements. The method used in developing multimedia products of this game uses MDLC (Multimedia Development Life Cycle). Based on the tests that have been carried out, the alpha test results are functionally appropriate and the results of beta testing using UserAcceptence Test (UAT) obtained a value of 86.40% which is declared feasible to use and can be developed. The advantages of this game are the presence of shock elements in the form of landslides, bursts of water, rock rain, and attacks by eagles

Programmable Electrofluidics for Ionic Liquid Based Neuromorphic Platform.

Due to the limit in computing power arising from the Von Neumann bottleneck, computational devices are being developed that mimic neuro-biological processing in the brain by correlating the device characteristics with the synaptic weight of neurons. This platform combines ionic liquid gating and electrowetting for programmable placement/connectivity of the ionic liquid. In this platform, both short-term potentiation (STP) and long-term potentiation (LTP) are realized via electrostatic and electrochemical doping of the amorphous indium gallium zinc oxide (aIGZO), respectively, and pulsed bias measurements are demonstrated for lower power considerations. While compatible with resistive elements, we demonstrate a platform based on transitive amorphous indium gallium zinc oxide (aIGZO) pixel elements. Using a lithium based ionic liquid, we demonstrate both potentiation (decrease in device resistance) and depression (increase in device resistance), and propose a 2D platform array that would enable a much higher pixel count via Active Matrix electrowetting.

Pore-scale hydrodynamics influence the spatial evolution of bacterial biofilms in a microfluidic porous network.

Bacteria occupy heterogeneous environments, attaching and growing within pores in materials, living hosts, and matrices like soil. Systems that permit high-resolution visualization of dynamic bacterial processes within the physical confines of a realistic and tractable porous media environment are rare. Here we use microfluidics to replicate the grain shape and packing density of natural sands in a 2D platform to study the flow-induced spatial evolution of bacterial biofilms underground. We discover that initial bacterial dispersal and grain attachment is influenced by bacterial transport across pore space velocity gradients, a phenomenon otherwise known as rheotaxis. We find that gravity-driven flow conditions activate different bacterial cell-clustering phenotypes depending on the strain’s ability to product extracellular polymeric substances (EPS). A wildtype, biofilm-producing bacteria formed compact, multicellular patches while an EPS-defective mutant displayed a linked-cell phenotype in the presence of flow. These phenotypes subsequently influenced the overall spatial distribution of cells across the porous media network as colonies grew and altered the fluid dynamics of their microenvironment.