Search results for "MULT"

Drug metabolism by cultured human hepatocytes: how far are we from the in vivo reality?

2004

The investigation of metabolism is an important milestone in the course of drug development. Drug metabolism is a determinant of drug pharmacokinetics variability in human beings. Fundamental to this are phenotypic differences, as well as genotypic differences, in the expression of the enzymes involved in drug metabolism. Genotypic variability is easy to identify by means of polymerase chain reaction-based or DNA chip-based methods, whereas phenotypic variability requires direct measurement of enzyme activities in liver, or, indirectly, measurement of the rate of metabolism of a given compound in vivo. There is a great deal of phenotypic variability in human beings, only a minor part being…

Kinase Inhibitors in Multitargeted Cancer Therapy

2017

The old-fashioned anticancer approaches, aiming in arresting cancer cell proliferation interfering with non-specific targets (e.g. DNA), have been replaced, in the last decades, by more specific target oriented ones. Nonetheless, single-target approaches have not always led to optimal outcomes because, for its complexity, cancer needs to be tackled at various levels by modulation of several targets. Although at present, combinations of individual single-target drugs represent the most clinically practiced therapeutic approaches, the modulation of multiple proteins by a single drug, in accordance with the polypharmacological strategy, has become more and more appealing. In the perspective of…

Drugs Polypharmacology by in Silico Methods: New Opportunities in Drug Discovery

2016

Background Polypharmacology, defined as the modulation of multiple proteins rather than a single target to achieve a desired therapeutic effect, has been gaining increasing attention since 1990s, when industries had to withdraw several drugs due to their adverse effects, leading to permanent injuries or death, with multi-billiondollar legal damages. Therefore, if up to then the "one drug one target" paradigm had seen many researchers interest focused on the identification of selective drugs, with the strong expectation to avoid adverse drug reactions (ADRs), very recently new research strategies resulted more appealing even as attempts to overcome the decline in productivity of the drug dis…

A deeper look into natural sciences with physics-based and data-driven measures

2021

Summary With the development of machine learning in recent years, it is possible to glean much more information from an experimental data set to study matter. In this perspective, we discuss some state-of-the-art data-driven tools to analyze latent effects in data and explain their applicability in natural science, focusing on two recently introduced, physics-motivated computationally cheap tools—latent entropy and latent dimension. We exemplify their capabilities by applying them on several examples in the natural sciences and show that they reveal so far unobserved features such as, for example, a gradient in a magnetic measurement and a latent network of glymphatic channels from the mous…

Early ERK1/2 activation promotes DRP1-dependent mitochondrial fission necessary for cell reprogramming.

2016

During the process of reprogramming to induced pluripotent stem (iPS) cells, somatic cells switch from oxidative to glycolytic metabolism, a transition associated with profound mitochondrial reorganization. Neither the importance of mitochondrial remodelling for cell reprogramming, nor the molecular mechanisms controlling this process are well understood. Here, we show that an early wave of mitochondrial fragmentation occurs upon expression of reprogramming factors. Reprogramming-induced mitochondrial fission is associated with a minor decrease in mitochondrial mass but not with mitophagy. The pro-fission factor Drp1 is phosphorylated early in reprogramming, and its knockdown and inhibition…

EGFL7 - a potential therapeutic target for multiple sclerosis?

2018

Analysis of normal human retinal vascular network architecture using multifractal geometry

2017

AIM To apply the multifractal analysis method as a quantitative approach to a comprehensive description of the microvascular network architecture of the normal human retina. METHODS Fifty volunteers were enrolled in this study in the Ophthalmological Clinic of Cluj-Napoca, Romania, between January 2012 and January 2014. A set of 100 segmented and skeletonised human retinal images, corresponding to normal states of the retina were studied. An automatic unsupervised method for retinal vessel segmentation was applied before multifractal analysis. The multifractal analysis of digital retinal images was made with computer algorithms, applying the standard box-counting method. Statistical analyse…

Inferring causation from time series in earth system sciences

2019

The heart of the scientific enterprise is a rational effort to understand the causes behind the phenomena we observe. In large-scale complex dynamical systems such as the Earth system, real experiments are rarely feasible. However, a rapidly increasing amount of observational and simulated data opens up the use of novel data-driven causal methods beyond the commonly adopted correlation techniques. Here, we give an overview of causal inference frameworks and identify promising generic application cases common in Earth system sciences and beyond. We discuss challenges and initiate the benchmark platform causeme.net to close the gap between method users and developers.

Mixed topological semimetals driven by orbital complexity in two-dimensional ferromagnets

2018

The concepts of Weyl fermions and topological semimetals emerging in three-dimensional momentum space are extensively explored owing to the vast variety of exotic properties that they give rise to. On the other hand, very little is known about semimetallic states emerging in two-dimensional magnetic materials, which present the foundation for both present and future information technology. Here, we demonstrate that including the magnetization direction into the topological analysis allows for a natural classification of topological semimetallic states that manifest in two-dimensional ferromagnets as a result of the interplay between spin-orbit and exchange interactions. We explore the emerg…

Long-range vortex transfer in superconducting nanowires

2019

Under high-enough values of perpendicularly-applied magnetic feld and current, a type-II superconductor presents a fnite resistance caused by the vortex motion driven by the Lorentz force. To recover the dissipation-free conduction state, strategies for minimizing vortex motion have been intensely studied in the last decades. However, the non-local vortex motion, arising in areas depleted of current, has been scarcely investigated despite its potential application for logic devices. Here, we propose a route to transfer vortices carried by non-local motion through long distances (up to 10 micrometers) in 50nm-wide superconducting WC nanowires grown by Ga+ Focused Ion Beam Induced Deposition.…