Метод лабораторного определения параметров устройства гидроимпульсного воздействия

Дана стаття описує лабораторний метод, що визначає: мету, умови, обсяг і порядок проведення досліджень параметрів пристрою гідроімпульсної дії.This article describes the laboratory method that defines: the purpose, conditions, effort and procedure of the researching the device settings of hydroimpulsive impact

When Noisy Neighbors Are a Blessing: Analysis of Gene Expression Noise Identifies Coregulated Genes

In this issue of Molecular Cell, Stewart-Ornstein et al. (2012) use systematic pair-wise correlation analysis of expression noise in a large number of yeast genes to identify clusters of functionally related genes and signaling pathways responsible for elevated noise

An analytical approach to modeling the stochastic behavior of visco-elastic materials

Stochastic fluctuations of material properties, i.e. the elastic constants, result in stochastic fluctuations of the material's response to mechanical loading, i.e. the stresses. In this contribution, we present an analytical approach to the time-efficient and mathematically accurate modeling of the stochastic behavior of visco-elastic materials. The material behavior is modeled using a viscous strain as an internal variable whose evolution is described by a differential equation. Since the stochastic material properties enter the evolution equation, a stochastic differential equation has to be treated which renders the problem rather uncomfortable. However, we present a precise investigation of the problem that yields a treatment similar to the deterministic case but resulting in the analytical estimation both of the expectation value and the variance (and standard deviation) of the stresses. A numerical comparison to Monte Carlo simulations proves the reliability of our approach

Single-molecule force spectroscopy distinguishes target binding modes of calmodulin

The eukaryotic signaling protein calmodulin (CaM) can bind to more than 300 known target proteins to regulate numerous functions in our body in a calcium-dependent manner. How CaM distinguishes between these various targets is still largely unknown. Here, we investigate fluctuations of the complex formation of CaM and its target peptide sequences using single-molecule force spectroscopy by AFM. By applying mechanical force, we can steer a single CaM molecule through its folding energy landscape from the fully unfolded state to the native target-bound state revealing equilibrium fluctuations between numerous intermediate states. We find that the prototypical CaM target sequence skMLCK, a fragment from skeletal muscle myosin light chain kinase, binds to CaM in a highly cooperative way, while only a lower degree of interdomain binding cooperativity emerges for CaMKK, a target peptide from CaM-dependent kinase kinase. We identify minimal binding motifs for both of these peptides, confirming that affinities of target peptides are not exclusively determined by their pattern of hydrophobic anchor residues. Our results reveal an association mode for CaMKK in which the peptide binds strongly to only partially Ca2+-saturated CaM. This binding mode might allow for a fine-tuning of the intracellular response to changes in Ca2+ concentration

Time-separated stochastic mechanics for simulating the visco-elastic response of construction parts

In a series of papers, we investigated the problem of efficiently analyzing visco-elastic materials with stochastic material properties. The related evolution equation could be solved analytically which allowed for a stochastic series expansion around the mean for the internal variable. This, in turn, gave access to analytical expressions for the stochastic stress and reaction force in a finite element setting such that expectation and variation could be expressed in terms of simple formulas. Consequently, our analysis separated the stochastic properties of the material from any boundary problem and any loads, i.e., the stochastic behavior was separated from all time-dependent conditions such that we referred our method as time-separated stochastic mechanics. Numerical results of our formulas were in excellent agreement to representative Monte-Carlo (MC) simulations. This holds true for both material point computations as well as finite element simulations. Particularly for finite element simulations, the time consumption for our approach is smaller by orders of magnitude. In this contribution, we recall the basic aspects of our works and present a brief overview. After presenting the key idea of the TSM, we recall the numerical treatment and present several examples which we compare to Monte-Carlo results. Our results show a similar quality as the reference solution but at a computational effort that is orders of magnitude smaller

Patched Receptors Sense, Interpret, and Establish an Epidermal Hedgehog Signaling Gradient

By using the sensitivity of single-molecule fluorescent in situ hybridization, we have precisely quantified the levels and defined the temporal and spatial distribution of Hedgehog signaling activity during embryonic skin development and discovered that there is a Hedgehog signaling gradient along the proximal-distal axis of developing hair follicles. To explore the contribution of Hedgehog receptors Ptch1 and Ptch2 in establishing the epidermal signaling gradient, we quantitated the level of pathway activity generated in Ptch1- and Ptch1;Ptch2-deficient skin and defined the contribution of each receptor to regulation of the levels of Hedgehog signaling identified in wild-type skin. Moreover, we show that both the cellular phenotype and level of pathway activity featured in Ptch1;Ptch2-deficient cells faithfully recapitulates the Peak level of endogenous Hedgehog signaling detected at the base of developing follicles, where the concentration of endogenous Shh is predicted to be highest. Taken together, these data show that both Ptch1 and Ptch2 play a crucial role in sensing the concentration of Hedgehog ligand and regulating the appropriate dose-dependent response

Spatio-temporal mRNA tracking in the early zebrafish embryo

Early stages of embryogenesis are known to depend on subcellular localization and transport of maternal mRNA, but systematic analyses have been hindered by a lack of methods for tracking of RNA. Here the authors combine spatially-resolved transcriptomics and single-cell RNA labeling to perform a spatio-temporal analysis of the transcriptome during early zebrafish development, revealing insights into this process