Dysregulations in the inflammatory response of body to pathogens could progress toward a hyperinflammatory condition amplified by positive feedback loops and associated with increased severity mortality. Hence, there is need for identifying therapeutic targets modulate this pathological immune response. Here, we propose single cell-based computational methodology predicting proteins dysregulated based on reconstruction analysis functional cell-cell communication networks physiological...

Oscillatory regulatory networks have been discovered in many cellular pathways. An especially challenging area is studying dynamics of oscillators interacting with one another a population. Synchronization only and the simplest outcome such interaction. It suggested that depends on structure network. Phase-attractive (synchronizing) phase-repulsive coupling structures were distinguished for oscillators. In this paper, we question separation. We study an example two repressilators (artificial...

We model the dynamics of synthetic genetic oscillator Repressilator equipped with quorum sensing. In addition to a circuit 3 genes repressing each other in unidirectional manner, includes phase-repulsive type coupling module implemented as production small diffusive molecule—autoinducer (AI). show that autoinducer (which stimulates transcription target gene) is responsible for disappearance limit cycle (LC) through infinite period bifurcation and formation stable steady state (SSS)...

The molecular underpinnings of the uncontrolled release proinflammatory cytokines and chemokines ('cytokine storm'), which can cause organ damage even mortality, are not completely understood. Furthermore, targeted therapeutic options to dampen such hyperinflammation scarce. Here, we highlight ways in technological advances have set stage for a new age synergy between experimental computational researchers guide discovery novel targets modulating hyperinflammation. Hyperinflammation, or...

We studied the behaviour of repressilator at 28 °C, 30 33 and 37 °C. From fluorescence in each cell over time, we determined period oscillations, functionality (fraction cells exhibiting oscillations) robustness expected oscillations that occur) this circuit. show oscillatory dynamics differs with temperature. Functionality is maximized Robustness decreases beyond as most exhibit 'failed' oscillations. These failures cause distribution periods to become bimodal, an 'apparent period' minimal...

<ja:p>We introduce a general procedure to match stochastic functional-structural tree model (here LIGNUM augmented with rules) real structures depicted by quantitative structure models (QSMs) based on terrestrial laser scanning. The matching is done iteratively finding the maximum correspondence between measured and choices of algorithm. First, we analyze synthetic data (generated itself), where target values parameters be estimated are known in advance, show that algorithm converges...

We study complex scaling properties of RR and QT intervals electrocardiograms (ECGs) with their equivalences at the cellular level, that is, inter-beat (IBI) field potential durations (FPD) spontaneously beating human-induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) aggregates. Our detrended fluctuation analysis Poincaré plots reveal remarkable similarities between ECG hiPSC-CM data. In particular, no statistically significant difference was found in short- long-term exponents...

We study the dynamics of a model stochastic two-gene switch at nucleotide and codon levels. First, we show that its stability, mean lifetime noisy attractors, differs from where transcription translation elongation are modeled as single-step delayed events, indicating need detailed models to switches. Next, vary coupling between two genes by varying affinity repressor proteins promoters measure mutual information times series. find there is degree maximizes propagation genes. This explained...

Abstract The relation between the electrical properties of heart and beating rate is essential for functioning. This central when calculating “corrected QT interval” — an important measure risk potentially lethal arrhythmias. We use transfer entropy method from information theory to quantitatively study mutual dynamics ventricular action potential duration (the interval) length beat-to-beat (RR) interval. show that healthy individuals there a strong asymmetry in transfer: flow RR dominates...

Abstract Detailed and realistic tree form generators have numerous applications in ecology forestry. For example, the varying morphology of trees contributes differently to formation landscapes, natural habitats species, eco-physiological characteristics biosphere. Here, we present an algorithm for generating morphological “clones” based on detailed reconstruction laser scanning data, statistical measure similarity, a plant growth model with simple stochastic rules. The is designed produce...

The assumption of the fast binding transcription factors (TFs) to promoters is a typical point in studies synthetic genetic circuits functioning bacteria. Although effective for simplifying models, it becomes questionable light vivo measurements times TF spends searching its cognate DNA sites. We investigated dynamics full idealized model paradigmatic oscillator, repressilator, using deterministic mathematical modelling and stochastic simulations. found (using experimentally approved...

Sauna sessions and winter swimming are traditional popular recreational activities in certain countries.Their positive effects on health relaxation, both as separate combined activities, commonly reported.However, systematic studies of these relatively scarce, especially regarding the nonlinear analysis physiological measurements heart activity.We performed Multi-Scale Entropy (MSE) Detrended Fluctuation (DFA) analyses inter-beat time series (about 72 h long) 21 healthy volunteers studied...

Abstract Programmed cell death mechanisms are important for the regulation of tumor development and progression. Evasion resistance to apoptosis significant factors in tumorigenesis drug resistance. Bypassing apoptotic pathways eliciting another form regulated death, namely necroptosis, an immunogenic (ICD), may override Here, we present mechanistic rationale combining tolinapant, antagonist inhibitor proteins (IAP), with decitabine, a hypomethylating agent (HMA), T-cell lymphoma (TCL)....

&lt;p&gt;Figure S2. Additional viability and cytokine data from each TCL CRISPR clone experiment. (Refers to Figure 1)&lt;/p&gt;

&lt;p&gt;Table S1. Details of primary antibodies used in Western blots this study (Figures 1,2,4,6 &amp; S1).&lt;/p&gt;

&lt;div&gt;Abstract&lt;p&gt;Programmed cell death mechanisms are important for the regulation of tumor development and progression. Evasion resistance to apoptosis significant factors in tumorigenesis drug resistance. Bypassing apoptotic pathways eliciting another form regulated death, namely necroptosis, an immunogenic (ICD), may override Here, we present mechanistic rationale combining tolinapant, antagonist inhibitor proteins (IAP), with decitabine, a hypomethylating agent (HMA), T-cell...

&lt;p&gt;Measurement of gene expression changes in TCL cell lines after treatment with decitabine &lt;i&gt;in vitro&lt;/i&gt;. &lt;b&gt;A,&lt;/b&gt; Western blots human (H9 and Karpas-299) mouse (BW5147 CT26) lysates prepared for 4 days (human) or 2 (mouse). Dotted indicate a cropped blot presentation purposes. &lt;b&gt;B,&lt;/b&gt; Bisulfite pyrosequencing data from four lines, showing basal (untreated) levels RIPK3 promoter methylation (top left), concentration-dependent decrease all...

&lt;p&gt;Synergistic interaction between decitabine and tolinapant in reducing viability of TCL cell lines &lt;i&gt;in vitro.&lt;/i&gt; Viability data obtained using CTG H9 cells (&lt;b&gt;A&lt;/b&gt; &lt;b&gt;B&lt;/b&gt;) BW5147 (&lt;b&gt;C&lt;/b&gt; &lt;b&gt;D&lt;/b&gt;) after 3 days treatment with a combination (A C) raw (B D) HSA score from ComBenefit synergy analysis. &lt;b&gt;E,&lt;/b&gt; Heat map showing change AUC measurements 3-day assays five different human lines, testing the (for...

&lt;p&gt;Table S1. Details of primary antibodies used in Western blots this study (Figures 1,2,4,6 &amp; S1).&lt;/p&gt;

&lt;p&gt;Figure S9. Analysis of tumor and plasma samples from EL4-Parental EL4-C8KO syngeneic model PD studies (Refers to Figure 6)&lt;/p&gt;

&lt;p&gt;Figure S8. Additional EL4 &amp; EL4-C8KO model in vivo efficacy data. (Refers to Figure 6)&lt;/p&gt;

&lt;p&gt;Figure S8. Additional EL4 &amp; EL4-C8KO model in vivo efficacy data. (Refers to Figure 6)&lt;/p&gt;