scholarly journals Bridging cell-scale simulations and radiologic images to explain short-time intratumoral oxygen fluctuations

2021 ◽  
Vol 17 (7) ◽  
pp. e1009206
Author(s):  
Jessica L. Kingsley ◽  
James R. Costello ◽  
Natarajan Raghunand ◽  
Katarzyna A. Rejniak

Radiologic images provide a way to monitor tumor development and its response to therapies in a longitudinal and minimally invasive fashion. However, they operate on a macroscopic scale (average value per voxel) and are not able to capture microscopic scale (cell-level) phenomena. Nevertheless, to examine the causes of frequent fast fluctuations in tissue oxygenation, models simulating individual cells’ behavior are needed. Here, we provide a link between the average data values recorded for radiologic images and the cellular and vascular architecture of the corresponding tissues. Using hybrid agent-based modeling, we generate a set of tissue morphologies capable of reproducing oxygenation levels observed in radiologic images. We then use these in silico tissues to investigate whether oxygen fluctuations can be explained by changes in vascular oxygen supply or by modulations in cellular oxygen absorption. Our studies show that intravascular changes in oxygen supply reproduce the observed fluctuations in tissue oxygenation in all considered regions of interest. However, larger-magnitude fluctuations cannot be recreated by modifications in cellular absorption of oxygen in a biologically feasible manner. Additionally, we develop a procedure to identify plausible tissue morphologies for a given temporal series of average data from radiology images. In future applications, this approach can be used to generate a set of tissues comparable with radiology images and to simulate tumor responses to various anti-cancer treatments at the tissue-scale level.

2021 ◽  
Author(s):  
Jessica L. Kingsley ◽  
James R. Costello ◽  
Natarajan Raghunand ◽  
Katarzyna A. Rejniak

AbstractRadiologic images provide a way to monitor tumor development and its response to therapies in a longitudinal and minimally invasive fashion. However, they operate on a macroscopic scale (average value per voxel) and are not able to capture microscopic scale (cell level) phenomena. Nevertheless, to examine the causes of frequent fast fluctuations in tissue oxygenation, the models simulating individual cells’ behavior are needed. Here, we provided a link between the average data value recorded for radiologic image voxels and the cellular and vascular architecture of the tissue that fills these voxels. Using hybrid agent-based modeling, we generated a set of tissue morphologies capable of reproducing tissue oxygenation levels observed in radiologic images. We applied this approach to investigate whether oxygen fluctuations can be explained by changes in vascular oxygen supply or by modulations in cellular oxygen absorption. Our studies showed that intravascular changes in oxygen supply can reproduce the observed fluctuations in tissue oxygenation in all considered regions of interest. However, large magnitude fluctuations cannot be recreated by modifications in cellular absorption of oxygen in biologically feasible manner. Additionally, we developed a procedure to identify plausible tissue morphologies for a given temporal series of average data from radiology images. In future applications this approach can be used to generate a set of tissues representative for radiology images and to simulate tumor response to various anti-cancer treatments on the tissue-scale level.Authors SummaryLow levels of oxygen, called hypoxia, are observable in many solid tumors. They are associated with more aggressive malignant cells which are resistant to chemo-, radio- and immunotherapies. Recently developed imaging techniques provide a way to measure the magnitude of frequent short-term oxygen fluctuation, however they operate on a macro-scale voxel level. To examine the causes of rapid oxygen fluctuations on the cell level, we developed a hybrid agent-based mathematical model. We tested two different mechanisms that could be responsible for these cyclic effects in tissue oxygenation: variations in vascular influx of oxygen and modulations in cellular oxygen absorption. Additionally, we developed a procedure to identify plausible tissue morphologies from data collected from radiological images. This will also provide a bridge between the micro-scale simulations with individual cells and the longitudinal medical images containing average voxel values. In the future applications, this approach can be used to generate a set of tissues representative of radiology images and to simulate tumor response to various anticancer treatments on the cell-scale level.


1953 ◽  
Vol 26 (3) ◽  
pp. 655-673 ◽  
Author(s):  
A. G. Veith

Abstract The nonrubber content of typical samples of all grades of technically classified rubber has been determined. It is found that the nonrubber content increases in the order: red, yellow, and blue. The chemical analyses performed to determine the nonrubber content were as follows: per cent ash, per cent nitrogen, per cent acetone extract, and per cent fatty acid. The pH of both a slurry of the ash and the aqueous digest indicates that blue rubber is more basic in these respects than are red and yellow rubbers. The measurement of the cure rate of these samples of technically classified rubber has been carried out by means of (1) conventional stress-strain testing, (2) the present ASTM method utilizing the Mooney viscometer, (3) the National Bureau of Standards strain test, (4) a new and more quantitative approach developed by Gee and coworkers, and (5) a utilization of the Mooney viscometer to determine two of the parameters of Gee's equation which gives the time dependence of modulus. All of these methods place the rubbers in the same relative order. The use of the viscometer to determine two of the parameters of Gee's equation was prompted by the degree of correlation between the rate parameter obtained with the present ASTM method and the rate constant k calculated by Gee's methods. As a result of a preliminary investigation as to the causes of viscosity increases at curing temperatures, it was found that, within limits of experimental error, all of the viscosity increase is due to the formation of a cross-linked network, with a linear relationship existing between viscosity increase ΔVc and modulus (at 100 per cent elongation) f. The results of a comparison of the rate constants obtained by the viscometer and by Gee's method indicate that for MBT mixes at 260° F there is good agreement between the methods. Statistical analysis shows that the samples employed for this study are significantly different in their rate of cure. The variance, range, and mean of some of the parameters obtained with the viscometer over a 10-week period are also given. It is suggested that the Mooney viscometer be employed to classify natural rubber according to its cure rate. If this is done, it will be necessary to define the degree of accuracy desired. To determine accurately the cure rate, it is necessary that the viscometer be used in conjunction with a press cure for the estimation of the parameter f∞. If it is not feasible to carry out press cures, an average value for f∞ can be assumed, and then only a short time test with the viscometer is required.


Author(s):  
Raja Al-Jaljouli ◽  
Jemal H. Abawajy

E-negotiation handles negotiation over the Internet without human supervision and has shown effectiveness in concluding verifiable and more favorable agreements in a reasonably short time. In this chapter, the authors discuss the negotiation system and its components with particular emphasis on negotiation strategies. A negotiation strategy defines strategic tactics, which advise on the proper action to select from a set of possible actions that optimizes negotiation outcomes. A strategy should integrate negotiation goals and reactive attitudes. Usually, a fixed strategy is implemented during the course of negotiation regardless of significant decision-making factors including market status, opponent’s profile, or eagerness for a negotiated goods/service. The chapter presents the main negotiation strategies and outlines the different decision-making factors that should be considered. A strategy uses a utility function to evaluate the offer of an opponent and advises on the generation of a counter offer or the best interaction. The authors finally discuss different utility functions presented in the literature.


2003 ◽  
Vol 13 (1) ◽  
pp. 51-54 ◽  
Author(s):  
P. Vedanthan

Yoga Breathing techniques (YBT) have been in vogue as an adjunct treatment in the management of asthma. The current study was done to determine the value of YBT in patients with COPD. Eleven patients (6 male, 5 female) in the age range 61–82 years (mean age 72) with an established diagnosis of COPD volunteered to participate in the study. Written consents were obtained prior to start of the study. All subjects were taught the YBT and relaxation techniques by a senior Yoga teacher. The procedure for YBT used in this group was modified to accommodate the limited physical capabilities of the participants due to their age as well as the severity of their COPD. The techniques involved breathing exercises with hand stretching, guided relaxation,sectional breathing, and meditation. All the participants received recorded audiotapes so that they could practice these techniques at home for a period of one week prior to the study. All the subjects were on continuous supplemental oxygen 1–3 liters per minute via nasal prongs. On the study day, baseline vital signs (blood pressure,pulse rate) were taken, a physical examination was done, and spirometry and oximetry were performed and readings recorded. The supplemental oxygen supply was stopped and subjects were asked to perform the YBT off oxygen. The subjects were closely watched and supervised by the Yoga teacher, as well as by the principal physician investigator, during this procedure. Continuous oximetry readings were taken and readings were recorded at baseline, 10 minutes, and 20 minutes during the performance of the YBT. Pre- and post-Yoga spirometry also was performed and recorded. All the subjects were requested to write down their impressions of the effect of YBT. Results: Oxygen saturation dropped to an average value of 87% (range: 82%–92%) immediately after the oxygen supply was discontinued. The oximetry values rose at 10 minutes to 92% and at 20 minutes to 94% during theYBT session on room air alone (without the use of supplemental oxygen). Ten out of 11 subjects felt subjectively better and relaxed overall. One subject could not tolerate being off oxygen, but still felt better subjectively during YBT. Spirometry values before and after YBT did not show any significant change. Conclusion:YBT seems to offer some benefit to patients with COPD and emphysema.


1997 ◽  
Vol 12 (2) ◽  
pp. 332-337 ◽  
Author(s):  
Toshihiro Kasuga ◽  
Koichi Nakamura ◽  
Tetsuji Hattori ◽  
Yoshihiro Abe

The melt of Bi–Sr–Ca–Cu–O (BSCCO) was quenched by splatting using iron plates, resulting in formation of the glassy plates (0.3–0.7 mm thickness). The plates were converted into superconductors by reheating in air. The critical temperature, Tc, depends on the thickness. The change in Tc is discussed in terms of the difference in the amount of oxygen absorption and in crystallization behavior of the glassy plate during the reheating process between the glassy phase in the interior and that around the surface. It was found that high-Tc glass-ceramic thin plates can be prepared by controlling the amount or the rate of oxygen supply.


2021 ◽  
Vol 14 (12) ◽  
pp. 1295
Author(s):  
Thabang Calvin Lebepe ◽  
Sundararajan Parani ◽  
Vuyelwa Ncapayi ◽  
Rodney Maluleke ◽  
Grace It Mwad Mbaz ◽  
...  

The cancer mortality rate has increased, and conventional cancer treatments are known for having many side effects. Therefore, it is imperative to find a new therapeutic agent or modify the existing therapeutic agents for better performance and efficiency. Herein, a synergetic phototherapeutic agent based on a combination of photothermal and photodynamic therapy is proposed. The phototherapeutic agent consists of water-soluble cationic porphyrin (5,10,15,20-tetrakis(N-methylpyridinium-3-yl)porphyrin, TMePyP), and gold nanorods (AuNRs) anchored on graphene-oxide (GO) sheet. The TMePyP was initially synthesized by Adler method, followed by methylation, while GO and AuNRs were synthesized using Hummer’s and seed-mediated methods, respectively. The structural and optical properties of TMePyP were confirmed using UV-Vis, zeta analyzer, PL, FTIR and NMR. The formation of both GO and AuNRs was confirmed by UV-Vis-NIR, FTIR, TEM and zeta analyzer. TMePyP and AuNRs were anchored on GO to form GO@AuNRs-TMePyP nanocomposite. The as-synthesized nanocomposite was stable in RPMI and PBS medium, and, on irradiation, produced high heat than the bare AuNRs, with high photothermal efficiency. In addition, the nanocomposite produced higher singlet oxygen than TMePyP with high biocompatibility in the absence of light. These results indicated that the as-synthesized nanocomposite is a promising dual photodynamic and photothermal agent for cancer therapy.


2021 ◽  
Vol 22 (17) ◽  
pp. 9191
Author(s):  
Diego Rodriguez ◽  
Deepika Watts ◽  
Diana Gaete ◽  
Sundary Sormendi ◽  
Ben Wielockx

Every cell in the body requires oxygen for its functioning, in virtually every animal, and a tightly regulated system that balances oxygen supply and demand is therefore fundamental. The vascular network is one of the first systems to sense oxygen, and deprived oxygen (hypoxia) conditions automatically lead to a cascade of cellular signals that serve to circumvent the negative effects of hypoxia, such as angiogenesis associated with inflammation, tumor development, or vascular disorders. This vascular signaling is driven by central transcription factors, namely the hypoxia inducible factors (HIFs), which determine the expression of a growing number of genes in endothelial cells and pericytes. HIF functions are tightly regulated by oxygen sensors known as the HIF-prolyl hydroxylase domain proteins (PHDs), which are enzymes that hydroxylate HIFs for eventual proteasomal degradation. HIFs, as well as PHDs, represent attractive therapeutic targets under various pathological settings, including those involving vascular (dys)function. We focus on the characteristics and mechanisms by which vascular cells respond to hypoxia under a variety of conditions.


2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Manish Gupta ◽  
Jyotsna Mishra ◽  
K. S. Pitre

A study has been made on the mechanism of corrosion of mild steel and the effect of nitrilo trimethylene phosphonic (NTMP) acid as a corrosion inhibitor in acidic medium, that is, 10% HC1 using the weight loss method and electrochemical techniques, that is, potentiodynamic and galvanostatic polarization measurements. Although corrosion is a long-time process, but it takes place at a faster rate in the beginning which goes on decreasing with due course of time. The above-mentioned methods of corrosion rate determination furnish an average value for a long-time interval. Looking at the versatility and minimum detection limit of the voltammetric method, the authors have developed a new voltammetric method for the determination of corrosion rate at short-time intervals. The results of corrosion of mild steel in 10% HC1 solution with and without NTMP inhibitor at short-time intervals have been reported. The corrosion inhibition efficiency of NTMP is 93% after 24 h.


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