Supravital fluorometric apoptosis detection in a single mouse embryo using lab-on-a-chip

Detection of apoptosis is one of the main criteria of preimplantation embryo growth potential assessment. Recent developments in lab-on-a-chip techniques has led to apoptosis detection and monitoring on a single cell or embryo level. However, single embryo apoptosis detection without a change in embryo developmental competence and post-examination "recovery" still remains a challenge. In this paper we present a lab-on-a-chip, co-working with miniaturized optical instrumentation, which allows supravital examination of single embryos for the presence of apoptotic blastomers with full after lab-on-a-chip study "recovery" and maintenance of their further developmental capacity.     

On typically real functions which are generated by a fixed typically real function

Let T be the family of all typically real functions, i.e. functions that are analytic in the unit disk Δ:= {z ∈ ℂ: |z| < 1}, normalized by f(0) = f′(0) − 1 = 0 and such that Imz Im f(z) ⩾ 0 for z ∈ Δ.     

History-dependent subdifferential inclusions and hemivariational inequalities in contact mechanics

We consider a class of subdifferential inclusions involving a history-dependent term for which we provide an existence and uniqueness result. The proof is based on arguments on pseudomonotone operators and fixed point. Then we specialize this result in the study of a class of history-dependent hemivariational inequalities. Such kind of problems arises in a large number of mathematical models which describe quasistatic processes of contact between a deformable body and an obstacle, the so-called foundation. To provide an example we consider a viscoelastic problem in which the frictional contact is modeled with subdifferential boundary conditions. We prove that this problem leads to a history-dependent hemivariational inequality in which the unknown is the velocity field. Then we apply our abstract result in order to prove the unique weak solvability of the corresponding contact problem.     

Strong immersion is a well-quasi-ordering for semicomplete digraphs

We prove that the strong immersion order is a well-quasi-ordering on the class of semicomplete digraphs, thereby strengthening a result of Chudnovsky and Seymour (2011, J. Comb. Theory, Series B, 101, 47–53) that this holds for the class of tournaments.     

Differential Tests for Plurisubharmonic Functions and Koch Curves

Potential Analysis - We study minimum sets of singular plurisubharmonic functions and their relation to upper contact sets. In particular we develop an algorithm checking when a naturally...     

Geometric properties of F-normed Orlicz spaces

Aequationes mathematicae - The paper deals with F-normed functions and sequence spaces. First, some general results on such spaces are presented. But most of the results in this paper concern...     

Phase transformation in shape memory alloys: a numerical approach for thermomechanical modeling via peridynamics

Meccanica - The work is devoted to the numerical aspects of the modeling tool elaborated to simulate the phenomenon of solid phase transformation in shape memory alloys. Particularly, a nonlocal...     

Quasi-arithmetic-type invariant means on probability space

Aequationes mathematicae - For a family $$(\mathscr {A}_x)_{x \in (0,1)}$$ of integral quasi-arithmetic means satisfying certain measurability-type assumptions we search for an integral mean K such...     

5-(Indol-2-yl)pyrazolo[3,4-b]pyridines as a New Family of TASK-3 Channel Blockers: A Pharmacophore-Based Regioselective Synthesis

TASK channels belong to the two-pore-domain potassium (K_2P) channels subfamily. These channels modulate cellular excitability, input resistance, and response to synaptic stimulation. TASK-channel inhibition led to membrane depolarization. TASK-3 is expressed in different cancer cell types and neurons. Thus, the discovery of novel TASK-3 inhibitors makes these bioactive compounds very appealing to explore new cancer and neurological therapies. TASK-3 channel blockers are very limited to date, and only a few heterofused compounds have been reported in the literature. In this article, we combined a pharmacophore hypothesis with molecular docking to address for the first time the rational design, synthesis, and evaluation of 5-(indol-2-yl)pyrazolo[3,4-b]pyridines as a novel family of human TASK-3 channel blockers. Representative compounds of the synthesized library were assessed against TASK-3 using Fluorometric imaging plate reader—Membrane Potential assay (FMP). Inhibitory properties were validated using two-electrode voltage-clamp (TEVC) methods. We identified one active hit compound (MM-3b) with our systematic pipeline, exhibiting an IC₅₀ ≈ 30 μM. Molecular docking models suggest that compound MM-3b binds to TASK-3 at the bottom of the selectivity filter in the central cavity, similar to other described TASK-3 blockers such as A1899 and PK-THPP. Our in silico and experimental studies provide a new tool to predict and design novel TASK-3 channel blockers.