scholarly journals Nonlinear active control of a cancerous tumour

2018 ◽  
Vol 7 (2.21) ◽  
pp. 72 ◽  
Author(s):  
Bhabani Shankar Dey ◽  
Manas Kumar Bera ◽  
Binoy Krishna Roy
Keyword(s):  
Active Control ◽  
Immune Cells ◽  
Normal Cell ◽  
Tumour Growth ◽  
Three Dimensional ◽  
Tumour Cells ◽  
Host Cells ◽  
Cancer Model ◽  
Control Objective ◽  
Simulation Results

This paper deals with the control of a cancerous tumour growth. The model used is a Three-Dimensional Cancer Model (TDCM). The competition terms include tumour cells, healthy cells, and immune cells. Nature of the competition among the populations of tumour cells, healthy host cells, and immune cells results in a chaotic behaviour. In this paper, a nonlinear active control has been used to control the growth of a tumour. Effect of chemotherapy drug on the different cell populations has been studied. Our control objective is to control the tumour growth and minimize its population to a small value which can be considered as harmless.Along with the above objective, the normal cell population is also be maintained at a particular level. This work has been done completely inin-sillico environment. The simulation results are shown extensively to support the theoretical analysis and confirmed that the preliminary objectives of the paper are attained.  

scholarly journals A Bioengineered Three-Dimensional Cell Culture Platform Integrated with Microfluidics To Address Antimicrobial Resistance in Tuberculosis

mBio ◽  
2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Magdalena K. Bielecka ◽  
Liku B. Tezera ◽  
Robert Zmijan ◽  
Francis Drobniewski ◽  
Xunli Zhang ◽  
...  
Keyword(s):  
Antimicrobial Resistance ◽  
Immune Cells ◽  
Three Dimensional ◽  
Host Cells ◽  
Bacterial Survival ◽  
Dimensional Matrix ◽  
Concentration Changes ◽  
Model Drug ◽  
Global Threat ◽  
New Treatments

ABSTRACT Antimicrobial resistance presents one of the most significant threats to human health, with the emergence of totally drug-resistant organisms. We have combined bioengineering, genetically modified bacteria, longitudinal readouts, and fluidics to develop a transformative platform to address the drug development bottleneck, utilizing Mycobacterium tuberculosis as the model organism. We generated microspheres incorporating virulent reporter bacilli, primary human cells, and an extracellular matrix by using bioelectrospray methodology. Granulomas form within the three-dimensional matrix, and mycobacterial stress genes are upregulated. Pyrazinamide, a vital first-line antibiotic for treating human tuberculosis, kills M. tuberculosis in a three-dimensional culture but not in a standard two-dimensional culture or Middlebrook 7H9 broth, demonstrating that antibiotic sensitivity within microspheres reflects conditions in patients. We then performed pharmacokinetic modeling by combining the microsphere system with a microfluidic plate and demonstrated that we can model the effect of dynamic antibiotic concentrations on mycobacterial killing. The microsphere system is highly tractable, permitting variation of cell content, the extracellular matrix, sphere size, the infectious dose, and the surrounding medium with the potential to address a wide array of human infections and the threat of antimicrobial resistance. IMPORTANCE Antimicrobial resistance is a major global threat, and an emerging concept is that infection should be studied in the context of host immune cells. Tuberculosis is a chronic infection that kills over a million people every year and is becoming progressively more resistant to antibiotics. Recent major studies of shorter treatment or new vaccination approaches have not been successful, demonstrating that transformative technologies are required to control tuberculosis. We have developed an entirely new system to study the infection of host cells in a three-dimensional matrix by using bioengineering. We showed that antibiotics that work in patients are effective in this microsphere system but not in standard infection systems. We then combined microspheres with microfluidics to model drug concentration changes in patients and demonstrate the effect of increasing antibiotic concentrations on bacterial survival. This system can be widely applied to address the threat of antimicrobial resistance and develop new treatments. IMPORTANCE Antimicrobial resistance is a major global threat, and an emerging concept is that infection should be studied in the context of host immune cells. Tuberculosis is a chronic infection that kills over a million people every year and is becoming progressively more resistant to antibiotics. Recent major studies of shorter treatment or new vaccination approaches have not been successful, demonstrating that transformative technologies are required to control tuberculosis. We have developed an entirely new system to study the infection of host cells in a three-dimensional matrix by using bioengineering. We showed that antibiotics that work in patients are effective in this microsphere system but not in standard infection systems. We then combined microspheres with microfluidics to model drug concentration changes in patients and demonstrate the effect of increasing antibiotic concentrations on bacterial survival. This system can be widely applied to address the threat of antimicrobial resistance and develop new treatments.

scholarly journals Complement Inactivation Strategy of Staphylococcus aureus Using Decay-Accelerating Factor and the Response of Infected HaCaT Cells

2021 ◽  
Vol 22 (8) ◽  
pp. 4015
Author(s):  
Kyoung Ok Jang ◽  
Youn Woo Lee ◽  
Hangeun Kim ◽  
Dae Kyun Chung
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Cells ◽  
Respiratory Infections ◽  
Food Poisoning ◽  
Surface Expression ◽  
Host Cells ◽  
Hacat Cells ◽  
Decay Accelerating Factor ◽  
Ligand Expression ◽  
The Complement System

Staphylococcus aureus is a species of Gram-positive staphylococcus. It can cause sinusitis, respiratory infections, skin infections, and food poisoning. Recently, it was discovered that S. aureus infects epithelial cells, but the interaction between S. aureus and the host is not well known. In this study, we confirmed S. aureus to be internalized by HaCaT cells using the ESAT-6-like protein EsxB and amplified within the host over time by escaping host immunity. S. aureus increases the expression of decay-accelerating factor (CD55) on the surfaces of host cells, which inhibits the activation of the complement system. This mechanism makes it possible for S. aureus to survive in host cells. S. aureus, sufficiently amplified within the host, is released through the initiation of cell death. On the other hand, the infected host cells increase their surface expression of UL16 binding protein 1 to inform immune cells that they are infected and try to be eliminated. These host defense systems seem to involve the alteration of tight junctions and the induction of ligand expression to activate immune cells. Taken together, our study elucidates a novel aspect of the mechanisms of infection and immune system evasion for S. aureus.

scholarly journals D936Y and Other Mutations in the Fusion Core of the SARS-CoV-2 Spike Protein Heptad Repeat 1: Frequency, Geographical Distribution, and Structural Effect

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2622
Author(s):  
Romina Oliva ◽  
Abdul Rajjak Shaikh ◽  
Andrea Petta ◽  
Anna Vangone ◽  
Luigi Cavallo
Keyword(s):  
Three Dimensional ◽  
Salt Bridge ◽  
Structural Effect ◽  
Host Cells ◽  
Heptad Repeat ◽  
Genomic Sequences ◽  
Strong Interactions ◽  
Virus Infectivity ◽  
S Protein ◽  
Global Threat

The crown of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is constituted by its spike (S) glycoprotein. S protein mediates the SARS-CoV-2 entry into the host cells. The “fusion core” of the heptad repeat 1 (HR1) on S plays a crucial role in the virus infectivity, as it is part of a key membrane fusion architecture. While SARS-CoV-2 was becoming a global threat, scientists have been accumulating data on the virus at an impressive pace, both in terms of genomic sequences and of three-dimensional structures. On 15 February 2021, from the SARS-CoV-2 genomic sequences in the GISAID resource, we collected 415,673 complete S protein sequences and identified all the mutations occurring in the HR1 fusion core. This is a 21-residue segment, which, in the post-fusion conformation of the protein, gives many strong interactions with the heptad repeat 2, bringing viral and cellular membranes in proximity for fusion. We investigated the frequency and structural effect of novel mutations accumulated over time in such a crucial region for the virus infectivity. Three mutations were quite frequent, occurring in over 0.1% of the total sequences. These were S929T, D936Y, and S949F, all in the N-terminal half of the HR1 fusion core segment and particularly spread in Europe and USA. The most frequent of them, D936Y, was present in 17% of sequences from Finland and 12% of sequences from Sweden. In the post-fusion conformation of the unmutated S protein, D936 is involved in an inter-monomer salt bridge with R1185. We investigated the effect of the D936Y mutation on the pre-fusion and post-fusion state of the protein by using molecular dynamics, showing how it especially affects the latter one.

Design of finite-time guidance law based on observer and head-pursuit theory

2021 ◽  
pp. 095441002098456
Author(s):  
Chenqi Zhu
Keyword(s):  
Finite Time ◽  
Three Dimensional ◽  
Hypersonic Vehicle ◽  
Two Dimensional ◽  
Dimensional Model ◽  
Reaching Law ◽  
Guidance Law ◽  
Fast Power ◽  
Simulation Results ◽  
Guidance Laws

In order to improve the guiding accuracy in intercepting the hypersonic vehicle, this article presents a finite-time guidance law based on the observer and head-pursuit theory. First, based on a two-dimensional model between the interceptor and target, this study applies the fast power reaching law to head-pursuit guidance law so that it can alleviate the chattering phenomenon and ensure the convergence speed. Second, target maneuvers are considered as system disturbances, and the head-pursuit guidance law based on an observer is proposed. Furthermore, this method is extended to a three-dimensional case. Finally, comparative simulation results further verify the superiority of the guidance laws designed in this article.

Direct simulation of evolution and control of three-dimensional instabilities in attachment-line boundary layers

1995 ◽  
Vol 291 ◽  
pp. 369-392 ◽  
Author(s):  
Ronald D. Joslin
Keyword(s):  
Boundary Layer ◽  
Stokes Equations ◽  
Three Dimensional ◽  
Plate Boundary ◽  
Navier Stokes ◽  
Two Dimensional ◽  
Computationally Efficient ◽  
Simulation Results ◽  
Dimensional Simulation ◽  
Attachment Line

The spatial evolution of three-dimensional disturbances in an attachment-line boundary layer is computed by direct numerical simulation of the unsteady, incompressible Navier–Stokes equations. Disturbances are introduced into the boundary layer by harmonic sources that involve unsteady suction and blowing through the wall. Various harmonic-source generators are implemented on or near the attachment line, and the disturbance evolutions are compared. Previous two-dimensional simulation results and nonparallel theory are compared with the present results. The three-dimensional simulation results for disturbances with quasi-two-dimensional features indicate growth rates of only a few percent larger than pure two-dimensional results; however, the results are close enough to enable the use of the more computationally efficient, two-dimensional approach. However, true three-dimensional disturbances are more likely in practice and are more stable than two-dimensional disturbances. Disturbances generated off (but near) the attachment line spread both away from and toward the attachment line as they evolve. The evolution pattern is comparable to wave packets in flat-plate boundary-layer flows. Suction stabilizes the quasi-two-dimensional attachment-line instabilities, and blowing destabilizes these instabilities; these results qualitatively agree with the theory. Furthermore, suction stabilizes the disturbances that develop off the attachment line. Clearly, disturbances that are generated near the attachment line can supply energy to attachment-line instabilities, but suction can be used to stabilize these instabilities.

Key Technologies Research on Color Contour Map of 3D Injection Molding Simulation Results

2012 ◽  
Vol 217-219 ◽  
pp. 1998-2001
Author(s):  
Tie Geng ◽  
Qing Hai Ren ◽  
Wei Qing Tu ◽  
Dan Dan Liu
Keyword(s):  
Injection Molding ◽  
Color Image ◽  
Three Dimensional ◽  
Physical Field ◽  
Contour Map ◽  
Image Rendering ◽  
Color Range ◽  
Key Technologies ◽  
Injection Molding Simulation ◽  
Simulation Results

According to the color contour map of the 3D injection molding simulation results, the commonly used color contour map drawing algorithm was researched, and a three-dimensional color image rendering algorithm which based on the "physical field values and color range mapping" was given too. And the key technologies of the algorithm which was used to draw 3D color contour map were introduced in detail. In the end, an example was given.

scholarly journals A study about signal variation with minor receiver displacement in a meeting room at 60 GHz: measurements and simulations

2021 ◽  
Vol 2021 (1) ◽  
Author(s):  
Muhammad Usman Sheikh ◽  
Kalle Ruttik ◽  
Riku Jäntti ◽  
Jyri Hämäläinen
Keyword(s):  
Power Level ◽  
Three Dimensional ◽  
60 Ghz ◽  
System Configuration ◽  
Conference Room ◽  
Channel Characteristics ◽  
Received Power ◽  
Simulation Results ◽  
Small Change ◽  
The Impact

AbstractThe aim of this work is to study the impact of small receiver displacement on a signal propagation in a typical conference room environment at a millimeter wave frequency of 60 GHz. While channel measurements provide insights on the propagation phenomena, their use for the wireless system performance evaluation is challenging. Whereas, carefully executed three-dimensional ray tracing (RT) simulations represent a more flexible option. Nevertheless, a careful validation of simulation methodology is needed. The first target of this article is to highlight the benefits of an in-house built three-dimensional RT tool at 60 GHz and shows the effectiveness of simulations in predicting different characteristics of the channel. To validate the simulation results against the measurements, two different transmitter (Tx) positions and antenna types along with ten receiver (Rx) positions are considered in a typical conference room. In first system configuration, an omnidirectional antenna is placed in the middle of the table, while in the second system configuration a directed horn antenna is located in the corner of the meeting room. After validating the simulation results with the measurement data, in the second part of this work, the impact of a small change, i.e., 20 cm in the receiver position, is studied. To characterize the impact, we apply as performance indicators the received power level, root mean square delay spread (RMS-DS) and RMS angular spread (RMS-AS) in azimuth plane. The channel characteristics are considered with respect to the direct orientation (DO), i.e., the Rx antenna is directed toward the strongest incoming path. Different antenna configurations at the Tx and Rx side are applied to highlight the role of antenna properties on the considered channel characteristics. Especially, in the second system configuration the impact of different antenna half power beamwidth on different considered channel characteristics is highlighted through acquired simulation results. The validation of results shows the RMS error of only 2–3 dB between the measured and simulated received power levels for different Tx configurations in the direction of DO. Results indicate that only a small change of the Rx position may result a large difference in the received power level even in the presence of line-of-sight between the Tx and Rx. It is found that the STD of received power level across the room increases with the decrease in HPBW of the antenna. As can be expected, directed antennas offer lower value of RMS-DS and RMS-AS compared with isotropic antenna.

Abstract 1772: Cardiomyocyte Damage-Released S100A1 Protein Evokes A Proinflammatory Phenotype In Cardiac Fibroblasts

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
David Rohde ◽  
Melanie Boerries ◽  
Herzog Nicole ◽  
Gang Qiu ◽  
Philipp Ehlermann ◽  
...  
Keyword(s):  
Western Blotting ◽  
Immune Cells ◽  
Nuclear Translocation ◽  
Cardiac Fibroblasts ◽  
Innate Immune ◽  
Host Cells ◽  
Boyden Chamber ◽  
Innate Immune Cells ◽  
Danger Signal

Background: S100A1, a cardiomyocyte specific inotropic calcium sensor protein, is released from infarcted human myocardium in the extracellular environment and circulation, reaching peak serum levels (1–2 μM) 8–9 hours after clinical onset. As growing evidence indicates that S100 proteins can act as pre-existing danger signals triggering the innate immune system into action upon release from injured host cells, we hypothesized that damage-released S100A1 can act as a cardiac danger signal alerting innate immune cells. Methods and Results: Here we report for the first time that necrotic cardiomyocytes release S100A1 protein in vitro, which is exclusively internalized by cardiac fibroblasts (CFs) in a clathrin- and caveolin-independent manner as shown by IF. Internalized S100A1 specifically activated MAPKs/SAPKs (p38, ERK1/2 and JNK) resulting in nuclear translocation of p65 (NF-kB) as assessed by Western blotting, EMSA and IF. In turn, S100A1 triggered an inflammatory gene program in CFs including enhanced expression of adhesion molecules, integrins, chemokines and cytokines including I-CAM, V-CAM, CD11b/18, IL1-alpha, MCP-1, TNF-alpha, SDF-1 among others as obtained by RT-PCR, Western blotting and ELISA. This resulted in enhanced chemoattraction and adhesion of monocytotic and stem cells to S100A1-activated CF as shown by Boyden-chamber and adhesion assays. In line with their proinflammatory transition, S100A1-activated CFs exhibited decreased collagen-1/-3 expression and de-novo collagen production, enhanced collagenolytic MMP-9 abundance and activity and increased levels of the antiangiogenic matricellular factor thrombospondin-2 reflecting extracellular matrix net degradation. Importantly, the immun-modulatory and antifibrotic actions of S100A1 protein in vitro were restricted to CFs, RAGE independent and occurred at concentrations (0.1–1 μM) that were found in patients after AMI. Conclusion: Our in vitro results indicate that S100A1 has the properties of a pre-exisiting endogenous cardiomyocyte danger signal transforming cardiac fibroblasts into immunmodulatory cells that might recruit innate immune cells to the site of cardiac injury and link cardiomyocyte damage to post-MI inflammation.

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