An in vitro model of tumor heterogeneity resolves genetic, epigenetic, and stochastic sources of cell state variability.

Tumor heterogeneity is a primary cause of treatment failure and acquired resistance in cancer patients. Even in cancers driven by a single mutated oncogene, variability in response to targeted therapies is well known. The existence of additional genomic alterations among tumor cells can only partially explain this variability.

Experimental Validation of an Inductive System for Magnesium Level Detection in a Titanium Reduction Reactor.

In order to precisely determine the magnesium level in a titanium reduction retort by inductive methods, many interfering influences have to be considered. By using a look-up-table method, the magnesium level can be reliably identified by taking into account the interfering effects of the titanium sponge rings forming at the walls with their unknown geometrical and electrical parameters. This new method uses a combination of numerical simulations and measurements, whereby the simulation model is calibrated so that it represents the experimental setup as closely as possible.

Local Heating Test for Detection of Microcirculation Abnormalities in Patients with Diabetes-Related Foot Complications.

Objective: In this study, authors used a wavelet analysis of skin temperature (WAST) to assess the mechanisms of microvascular tone regulation during the local heating test in patients with diabetic foot syndrome (DFS).

Participants: The participants included control subjects and 36 hospitalized patients with DFS between 52 and 79 years old (68 ± 8 years old). They were distributed among 5 groups: 15 control subjects, 8 patients with DFS who did not develop ulcerative or necrotic disorders, 10 patients who developed the neuroischemic form of DFS complicated by foot ulceration, 12 patients with DFS complicated by toe necrosis, and 6 patients with DFS and foot gangrene.

Early differential diagnosis of the severity of acute pancreatitis.

There is a great need for early verification of the severity of acute pancreatitis (AP). The early stage of pathogenesis of AP is characterized by endothelial dysfunction which could be determined by wavelet analysis of skin temperature (WAST) technique. The aim is to investigate whether the dysregulation of microvascular tone caused by endothelial dysfunction and detected by WAST can be a significant indicator in early differential diagnosis of AP severity.

Relationship of oscillating and average components of laser Doppler flowmetry signal.

Signals from laser Doppler flowmeters widely used in intravital studies of skin blood flow include, along with a slowly varying average component, an oscillating part. However, in most clinical studies, pulsations are usually smoothed by data preprocessing and only the mean blood flow is analyzed. To reveal the relationship between average and oscillating perfusion components measured by a laser Doppler flowmeter, we examined the microvascular response to the contralateral cold pressor test recorded at two different sites of the hand: dorsal part of the arm and finger pad.

Detection of Endothelial Dysfunction Using Skin Temperature Oscillations Analysis During Local Heating in Patients With Peripheral Arterial Disease.

Objective: The purpose of this study was to examine correlations between laboratory markers of ED and the degree of endothelium-dependent vasodilation using WAST during a local heating test in patients with PAD.

Materials And Methods: The study population consisted of 17 healthy subjects and 38 patients with PAD. The ST on the plantar surface of the first toe was measured during the test, and the inverse wavelet transform was applied to reconstruct the ST signals in three frequency bands corresponding to myogenic, neurogenic, and endothelial mechanisms of vascular tone regulation.

An unbiased metric of antiproliferative drug effect in vitro.

In vitro cell proliferation assays are widely used in pharmacology, molecular biology, and drug discovery. Using theoretical modeling and experimentation, we show that current metrics of antiproliferative small molecule effect suffer from time-dependent bias, leading to inaccurate assessments of parameters such as drug potency and efficacy. We propose the drug-induced proliferation (DIP) rate, the slope of the line on a plot of cell population doublings versus time, as an alternative, time-independent metric.

Skin blood flow and temperature oscillations during cold pressor test.

We study the relationship between the blood flow and skin temperature variations under a cold pressor test (CPT). The simultaneous laser Doppler flowmetry (LDF) and skin temperature (ST) measurements were carried out for 8 healthy subjects on the skin surface of the distal phalanx of the second (LDF) and third (ST) fingers. The skin blood perfusion decreases stepwise about twice during contralateral CPT for all 8 subjects.

Hindered Energy Cascade in Highly Helical Isotropic Turbulence.

The conventional approach to the turbulent energy cascade, based on Richardson-Kolmogorov phenomenology, ignores the topology of emerging vortices, which is related to the helicity of the turbulent flow. It is generally believed that helicity can play a significant role in turbulent systems, e.g.

Quantifying the correlation between photoplethysmography and laser Doppler flowmetry microvascular low-frequency oscillations.

Photoplethysmography (PPG) and laser Doppler flowmetry (LDF) are two recognized optical techniques that can track low-frequency perfusion changes in microcirculation. The aim of this study was to determine, in healthy subjects, the correlation between the techniques for specific low-frequency bands previously defined for microcirculation. Twelve healthy male subjects (age range 18 to 50 years) were studied, with PPG and LDF signals recorded for 20 min from their right and left index (PPG) and middle (LDF) fingers.

Quantifying heterogeneity and dynamics of clonal fitness in response to perturbation.

The dynamics of heterogeneous clonal lineages within a cell population, in aggregate, shape both normal and pathological biological processes. Studies of clonality typically relate the fitness of clones to their relative abundance, thus requiring long-term experiments and limiting conclusions about the heterogeneity of clonal fitness in response to perturbation. We present, for the first time, a method that enables a dynamic, global picture of clonal fitness within a mammalian cell population.

Fractional proliferation: a method to deconvolve cell population dynamics from single-cell data.

We present an integrated method that uses extended time-lapse automated imaging to quantify the dynamics of cell proliferation. Cell counts are fit with a quiescence-growth model that estimates rates of cell division, entry into quiescence and death. The model is constrained with rates extracted experimentally from the behavior of tracked single cells over time.

Turbulent viscosity and turbulent magnetic diffusivity in a decaying spin-down flow of liquid sodium.

The free decay of a strong flow of liquid sodium (at Reynolds number defined via the maximal mean velocity and the radius of the channel cross section up to Re≈3×10(60) and the corresponding magnetic Reynolds number up to Rm≈30) generated by the sudden stop of a rapidly rotating toroidal channel is studied experimentally. The toroidal and poloidal components of velocity are measured using a potential probe. We describe the onset of motion, the evolution of strongly anisotropic fluctuations, and the homogenization and decay of turbulence in the final period.

Direct measurement of effective magnetic diffusivity in turbulent flow of liquid sodium.

The first direct measurements of effective magnetic diffusivity in turbulent flow of electroconductive fluids (the so-called β effect) under the magnetic Reynolds number Rm≫1 are reported. The measurements are performed in a nonstationary turbulent flow of liquid sodium, generated in a closed toroidal channel. The peak level of the Reynolds number reached Re≈3×10(6), which corresponds to the magnetic Reynolds number Rm≈30.

Wavelet-based correlations of skin temperature and blood flow oscillations.

The wavelet transform-based correlation analysis has been used to study skin temperature fluctuations caused by periodic changes in blood flow resulting from oscillations in vasomotor smooth muscle tone. We considered two cases, one in which temperature measurements and blood flow recordings by laser Doppler flowmetry are made simultaneously and another in which two temperature signals are measured concurrently. Twelve healthy subjects participated in our study.

Large- and small-scale interactions and quenching in an alpha2-dynamo.

The evolution of the large-scale magnetic field in a turbulent flow of conducting fluid is considered in the framework of a multiscale alpha2-dynamo model, which includes the poloidal and the toroidal components for the large-scale magnetic field and a shell model for the small-scale magnetohydrodynamical turbulence. The conjugation of the mean-field description for the large-scale field and the shell formalism for the small-scale turbulence is based on strict conformity to the conservation laws. The model displays a substantial magnetic contribution to the alpha effect.

Screw dynamo in a time-dependent pipe flow.

The kinematic dynamo problem is investigated for the flow of a conducting fluid in a cylindrical, periodic tube with conducting walls. The methods used are an eigenvalue analysis of the steady regime, and the three-dimensional solution of the time-dependent induction equation. The configuration and parameters considered here are close to those of a dynamo experiment planned in Perm, which will use a torus-shaped channel.

Interaction of the growth hormone receptor with cytokine-induced Src homology domain 2 protein in rat adipocytes.

GH stimulates the phosphorylation of tyrosine residues in the GH receptor (GHR), Janus kinase 2 (JAK2), and other signaling proteins in a transient manner that subsides within 1 h. To assess the possible roles of cytokine-induced Src homology domain 2 (SH2) (CIS/SOCS) proteins in these transient responses, we studied the expression and disposition of CIS/SOCS proteins in rat adipocytes, a physiological target of GH action. A tyrosine-phosphorylated protein that appears to be the GHR was coprecipitated from extracts of GH-treated adipocytes with alpha-CIS.