Electrocardiographic Consequences Of Electrical And Anatomical Remodeling In Diabetic And Obese Humans

Background. Diabetes and obesity are two major risk factors for cardiovascular disease. Both can cause changes due to cardiac sources in body-surface potentials: BSPs), that is, in electrocardiograms: ECGs). By identifying the major effects of diabetes and obesity on BSPs, we hope to reveal the electrical phenotype of diabetes in body-surface ECGs in the presence of obesity. Methods. A Bidomain Platform was constructed to link heart-surface transmembrane potentials: TMPs) and BSPs. The Forward-Problem Module of the platform calculates BSPs from a bidomain-model of myocyte TMPs and torso anatomy. The platform also contains a Cardio-myocyte TMP Estimation Module in which an innovative method, named regularized waveform identification: RWI), was developed. It is a new approach used to reconstruct the TMPs from BSPs, that is, solving the electrocardiographic inverse bidomain problem. Using normal TMPs, BSPs were simulated on obese torsos and compared to BSPs on a normal torso to determine ECG changes that might accompany certain obese habitus. BSPs on a normal torso were also simulated with both normal TMPs and TMPs whose duration was increased in a manner expected to occur in the diabetic. In addition, BSPs were measured, heart and torso models were found on two adult male subjects: one normal and one obese diabetic. BSPs and estimated TMPs in these subjects, found by using the RWI method, were compared to identify ECG changes that might be found in the obese diabetic in a clinical setting. Results. Forward-problem solutions found for obese heart-torso models with normal TMPs compared to normal had relative errors: RE) of 12, 30, and 68\% for 20\% left-ventricular hypertrophy, 16\% abdomen extension, and displaced heart, respectively. These results suggest that standard 12-lead ECG measurement could be significantly affected by the anatomical changes associated with obesity. Simulation results also showed diabetic electrical remodeling may have a strong impact on BSPs. An RE of 125\% was observed between normal and diabetic BSPs due to prolongation of recovery that might accompany diabetes. Energy reduction of BSPs was found in both simulated and measured BSPs with obesity. Although QT interval prolongation found in simulated BSPs was not seen in the ECGs recorded from the obese diabetic subject, QT dispersion(QTd) was found increased in diabetic in both simulated and measure ECGs. Obviously, no statistical conclusions can be reached with our limited data set, but the suggestive results call for further clinical observations. TMPs were estimated in realistic, normal heart-torso model simulations using the RWI method. REs of about 15\% were found for up to 10\% noise added to BSPs; and for errors in heart size of 10\% and heart location of $\pm 1$ cm, which were significant improvements over conventional regularization methods alone. Conclusions. In this study, we characterized electrical changes with diabetes and anatomical changes with obesity; then independently evaluated their influences on body surface potentials: BSPs). These results suggest that standard 12-lead ECG measurements could be strongly influenced by the anatomical changes associated with obesity. Body-surface maps and inverse solutions to the heart-surface that minimize volume-conductor effects are likely to be more useful in investigating the influence of diabetic electrical remodeling among obese diabetic patients. Simulation results showed that the RWI inverse solution performed much better than traditional regularization methods alone and is robust in the presence of noise and geometric error. By incorporating temporal information, in the form of the basic TMP wave shape, estimation accuracy was enhanced while maintaining computational simplicity

Gas-liquid two-phase flows in double inlet cyclones for natural gas separation

The gas-liquid two-phase flow within a double inlet cyclone for natural gas separation was numerically simulated using the discrete phase model. The numerical approach was validated with the experimental data, and the comparison results agreed well with each other. The simulation results showed that the strong swirling flow produced a high centrifugal force to remove the particles from the gas mixture. The larger particles moved downward on the internal surface and were removed due to the outer vortex near the wall. Most of the tiny particles went into the inner vortex zones and escaped from the up-outlet. The swirling flow was concentric due to the design of the double inlet for the cyclonic separator, which greatly improved the separating efficiency. The separating efficiency was greater than 90% with the particle diameter of more than 100 μm

On Six Solutions for m

Under the assumption of two coupled parallel subsuper solutions, the existence of at least six solutions for a kind of second-order m-point differential equations system is obtained using the fixed point index theory. As an application, an example to demonstrate our result is given

A hybrid performance evaluation approach for urban logistics using extended cross-efficiency with prospect theory and OWA operator

Urban logistics performance evaluation can provide reference for further improving its level. However, most performance evaluation for urban logistics premises that decision-makers (DMs) are completely rational, which may not conform to the actual situation. Therefore, this article aims to consider the DMs’ psychological factors in the performance evaluation of urban logistics. Specifically, the cross-efficiency evaluation (CEE) method with the DMs’ psychological factors is used to measure the urban logistics efficiency in the central area of Yangtze River Delta (YRD) urban agglomeration in China in 2019. The main contributions in this article are to propose a hybrid CEE method with prospect theory and ordered weighted average (OWA) operator for urban logistics industry and to expand the evaluation perspectives of urban logistics performance. The main conclusions are obtained: (1) The DMs’ optimism level can indeed affect the efficiency value and ranking of urban logistics. (2) The aggregation based on the OWA operator is fair and reasonable because it can make all self-evaluation efficiencies play the same role. (3) To make the efficiencies and rankings of urban logistics in the central area of the YRD have credibility and discrimination, the DMs’ optimism level range is best between 0.8 and 0.8177

Bayesian Inference of Phenotypic Plasticity of Cancer Cells Based on Dynamic Model for Temporal Cell Proportion Data

Mounting evidence underscores the prevalent hierarchical organization of cancer tissues. At the foundation of this hierarchy reside cancer stem cells, a subset of cells endowed with the pivotal role of engendering the entire cancer tissue through cell differentiation. In recent times, substantial attention has been directed towards the phenomenon of cancer cell plasticity, where the dynamic interconversion between cancer stem cells and non-stem cancer cells has garnered significant interest. Since the task of detecting cancer cell plasticity from empirical data remains a formidable challenge, we propose a Bayesian statistical framework designed to infer phenotypic plasticity within cancer cells, utilizing temporal data on cancer stem cell proportions. Our approach is grounded in a stochastic model, adept at capturing the dynamic behaviors of cells. Leveraging Bayesian analysis, we explore the moment equation governing cancer stem cell proportions, derived from the Kolmogorov forward equation of our stochastic model. With improved Euler method for ordinary differential equations, a new statistical method for parameter estimation in nonlinear ordinary differential equations models is developed, which also provides novel ideas for the study of compositional data. Extensive simulations robustly validate the efficacy of our proposed method. To further corroborate our findings, we apply our approach to analyze published data from SW620 colon cancer cell lines. Our results harmonize with \emph{in situ} experiments, thereby reinforcing the utility of our method in discerning and quantifying phenotypic plasticity within cancer cells

Pročišćavanje i karakterizacija fibrinolitičkog enzima iz plijesni Rhizopus microsporus var. tuberosus

Extracellular fibrinolytic enzyme from Rhizopus microsporus var. tuberosus was purified and characterised. The microorganism was isolated in a distillery from daqu, a fermentative agent used in the production of Chinese liquor and vinegar at diff erent temperatures. The fibrinolytic enzyme was partially purifi ed by ammonium sulphate precipitation, dialysis, DEAE Sepharose® Fast Flow ion exchange chromatography and Sephadex G-75 gel filtration chromatography. The molecular mass of the fi brinolytic enzyme was estimated to be 24.5 kDa by SDS-PAGE. The purified enzyme showed optimal activity at pH=7.0 and 37 °C by fibrin plate method. It showed stronger resistance to the inhibition by trypsin and was stable at 37 °C retaining 96.1 % residual activity aft er 4 h of incubation. The fibrinolytic activity of the enzyme was enhanced by Na+, Ca2+, Mg2+ and Mn2+. Conversely, Zn2+ and Cu2+ partly inhibited enzymatic activity. Using fibrin plate method, we found that the enzyme not only degrades fibrin directly, but also activates plasminogen into plasmin to degrade fibrin. The results indicate that the pure enzyme has a potential in dissolving blood clot, and the possibility for application in the treatment of thrombosis.U radu je pročišćen i ispitan izvanstanični fibrinolitički enzim iz plijesni Rhizopus microsporus var. tuberosus. Mikroorganizam je izoliran u distileriji iz starter kulture koja se koristi za fermentaciju tradicionalnog kineskog likera i octa pri različitim temperaturama, tzv. daqu. Fibrinolitički je enzim djelomično pročišćen taloženjem pomoću amonijevog sulfata, dijalizom, ionskom kromatografijom na koloni DEAE Sepharose Fast Flow i gel-filtracijskom kromatografijom na koloni Sephadex G-7. Molekularna masa fibrinolitičkog enzima, određena pomoću SDS-PAGE, iznosila je 24,5 kDa. Optimalni uvjeti za aktivnost pročišćenog enzima bili su pH=7,0 i 37 °C. Enzim je bio otporan na inhibiciju tripsinom, stabilan pri 37 °C, te je zadržao 96,1 % aktivnosti nakon 4 sata inkubacije. Fibrinolitička se aktivnost enzima pojačala u prisutnosti iona Na+, Ca2+, Mg2+ i Mn2+, dok su ioni Zn2+ i Cu2+ djelomično inhibirali njegovu aktivnost. Utvrđeno je da enzim izravno razgrađuje fibrin, i aktivira plazminogen, pri čemu nastali plazmin razgrađuje fibrin. Rezultati pokazuju da se pročišćeni enzim može primijeniti u liječenju tromboze, jer ima sposobnost razgradnje krvnih ugrušaka

MeDReaders: a database for transcription factors that bind to methylated DNA

Understanding the molecular principles governing interactions between transcription factors (TFs) and DNA targets is one of the main subjects for transcriptional regulation. Recently, emerging evidence demonstrated that some TFs could bind to DNA motifs containing highly methylated CpGs both in vitro and in vivo. Identification of such TFs and elucidation of their physiological roles now become an important stepping-stone toward understanding the mechanisms underlying the methylation-mediated biological processes, which have crucial implications for human disease and disease development. Hence, we constructed a database, named as MeDReaders, to collect information about methylated DNA binding activities. A total of 731 TFs, which could bind to methylated DNA sequences, were manually curated in human and mouse studies reported in the literature. In silico approaches were applied to predict methylated and unmethylated motifs of 292 TFs by integrating whole genome bisulfite sequencing (WGBS) and ChIP-Seq datasets in six human cell lines and one mouse cell line extracted from ENCODE and GEO database. MeDReaders database will provide a comprehensive resource for further studies and aid related experiment designs. The database implemented unified access for users to most TFs involved in such methylation-associated binding actives. The website is available at http://medreader.org/

Mitochondrial Glycerol Phosphate Acyltransferase Directs the Incorporation of Exogenous Fatty Acids into Triacylglycerol

The mitochondrial isoform of glycerol-3-phosphate acyltransferase (GPAT), the first step in glycerolipid synthesis, is up-regulated by insulin and by high carbohydrate feeding via SREBP-1c, suggesting that it plays a role in triacylglycerol synthesis. To test this hypothesis, we overexpressed mitochondrial GPAT in Chinese hamster ovary (CHO) cells. When GPAT was overexpressed 3.8-fold, triacylglycerol mass was 2.7-fold higher than in control cells. After incubation with trace [14C]oleate (∼3 μM), control cells incorporated 4.7-fold more label into phospholipid than triacylglycerol, but GPAT-overexpressing cells incorporated equal amounts of label into phospholipid and triacylglycerol. In GPAT-overexpressing cells, the incorporation of label into phospholipid, particularly phosphatidylcholine, decreased 30%, despite normal growth rate and phospholipid content, suggesting that exogenous oleate was directed primarily toward triacylglycerol synthesis. Transiently transfected HEK293 cells that expressed a 4.4-fold increase in GPAT activity incorporated 9.7-fold more [14C]oleate into triacylglycerol compared with control cells, showing that the effect of GPAT overexpression was similar in two different cell types that had been transfected by different methods. When the stable, GPAT-overexpressing CHO cells were incubated with 100 μM oleate to stimulate triacylglycerol synthesis, they incorporated 1.9-fold more fatty acid into triacylglycerol than did the control cells. Confocal microscopy of CHO and HEK293 cells transfected with the GPAT-FLAG construct showed that GPAT was located correctly in mitochondria and was not present elsewhere in the cell. These studies indicate that overexpressed mitochondrial GPAT directs incorporation of exogenous fatty acid into triacylglycerol rather than phospholipid and imply that (a) mitochondrial GPAT and lysophosphatidic acid acyltransferase produce a separate pool of lysophosphatidic acid and phosphatidic acid that must be transported to the endoplasmic reticulum where the terminal enzymes of triacylglycerol synthesis are located, and (b) this pool remains relatively separate from the pool of lysophosphatidic acid and phosphatidic acid that contributes to the synthesis of the major phospholipid species.Instituto de Investigaciones Bioquímicas de La Plat