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Simic-Krstic J.B.,University of Belgrade | Kalauzi A.J.,University of Belgrade | Ribar S.N.,University of Belgrade | Matija L.R.,University of Belgrade | Misevic G.N.,Gimmune GmbH
Experimental Gerontology | Year: 2014

A non-invasive bioimpedance spectroscopy (BIS) and Cole-Cole impedance model parameters (R0, R∞, τ and α) were used to analyze electrical properties of intact and stripped human skin for both gender subjects divided into younger and older age groups. R0, R∞ and τ significantly increased while α significantly decreased with age in stripped skin for both genders (p<0.031). Using pooled data with respect to age, gender and skin stripping, R0, R∞ and τ values were shown to increase with age (p<0.0034), R0, τ and α were different between genders (p<0.024) and R0, R∞ and τ decreased with skin stripping (p<0.000008). All of four Cole-Cole parameters were age dependent with specific differences observed for genders and intact and stripped skin layers. Therefore, Cole-Cole parameters, obtained by non-invasive BIS measurements, are a new type of age dependent biomarkers. © 2014 Elsevier Inc.

Vosika Z.B.,University of Belgrade | Lazovic G.M.,University of Belgrade | Misevic G.N.,Gimmune GmbH | Simic-Krstic J.B.,University of Belgrade
PLoS ONE | Year: 2013

Fractional calculus is a mathematical approach dealing with derivatives and integrals of arbitrary and complex orders. Therefore, it adds a new dimension to understand and describe basic nature and behavior of complex systems in an improved way. Here we use the fractional calculus for modeling electrical properties of biological systems. We derived a new class of generalized models for electrical impedance and applied them to human skin by experimental data fitting. The primary model introduces new generalizations of: 1) Weyl fractional derivative operator, 2) Cole equation, and 3) Constant Phase Element (CPE). These generalizations were described by the novel equation which presented parameter (β) related to remnant memory and corrected four essential parameters (R0,R∞,α,τα) We further generalized single generalized element by introducing specific partial sum of Maclaurin series determined by parameters (β*, γ, δ ...). We defined individual primary model elements and their serial combination models by the appropriate equations and electrical schemes. Cole equation is a special case of our generalized class of models for β* =γ=δ=...= 0. Previous bioimpedance data analyses of living systems using basic Cole and serial Cole models show significant imprecisions. Our new class of models considerably improves the quality of fitting, evaluated by mean square errors, for bioimpedance data obtained from human skin. Our models with new parameters presented in specific partial sum of Maclaurin series also extend representation, understanding and description of complex systems electrical properties in terms of remnant memory effects. © 2013 Vosika et al.

Misevic G.N.,Gimmune GmbH | Misevic N.,University of Bremen | Popescu O.,Babes - Bolyai University | Popescu O.,Romanian Academy of Sciences
Advances in Experimental Medicine and Biology | Year: 2012

The goal of this chapter is to make a specific contribution about glyconectin glycan as the self-assembling nano-molecular-velcro system mediating initial steps of self-nonself recognition and cell adhesion in Porifera, the first descendants of the most simple primordial multicellular organisms. Two original findings will be described: (i) Velcro like concept based on highly polyvalent and specific intermolecular glycan to glycan associations with extremely low affinity of the single binding site and (ii) novel structures of the large and newly emerging family of glyconectin like glycan molecules. The emphasis will be put on the interdisciplinary approach for studying structure to function relationship at the different size scale levels by combining the knowledge and technologies (instrumentation and methods) of physics, chemistry, biology and mathematics. Applying such strategy which is crossing the boundaries of different science disciplines enabled us to develop a new Atomic Force Microscopy (AFM) based nano-bio-technology and perform the first quantitative measurements of intermolecular binding forces at the single molecular level under physiological conditions. We propose that nano-velcro systems of the glyconectin glycans, which are the constituents on the cell surface that are the most exposed to the environment, were responsible for the molecular self-nonself recognition and adhesion processes that underpinned the emergence of multicellular life forms. © 2012 Landes Bioscience and Springer Science+Business Media.

Misevic G.N.,Gimmune GmbH | Benassayag G.,French National Center for Scientific Research | Rasser B.,Orsay Physics | Sales P.,French National Center for Scientific Research | And 3 more authors.
Journal of Molecular Structure | Year: 2014

Single cell 'omics' requires a technological platform with reliable and high throughput single cell analyses with single molecular detection and quantification. Presently available options are to either to detect many different macromolecules and metabolites extracted from many cells, thus obtaining partial 'omics' of an average cell or to study only few single cells and be limited to semi-quantitative analyses and detection of a few abundant molecules. Here we present a new design and prototype proof of concept construction of high throughput nano-electrophoretic separation (NEA) device and nano in micro array (NiMA) affinity probe device for a complete single cell 'omics' single bio-molecule polymers detection and quantification analyses. Prototype devices were constructed using gallium ion Focus Ion Beam (FIB), Gas Injection System (GIS) and Scanning Electron Microscope (SEM) crossbeam instruments. The NEA device accommodates 100 different cell samplings per 1 cm2 chip with arrays of open nano-electrophoretic guides. The NiMA bio-sensor device on 1 cm2 can accommodate 2500 cells in a micro-well array which consists of 250,000 probe markers in nano-well array located in each micro-well. Using Secondary Ion Mass Spectrometry (SIMS) we have demonstrated the direct detection of a single protein molecule and proved the feasibility of single bio-molecular detection and quantification concept for NEA and NIMA. Our concept validates high throughput and complete and quantitative single cell 'omics' with single molecular detection analyses without labeling. Thus, it is superior to commonly used microfluidics, capillary electrophoresis and micro-arrays using mass spectrometry and fluorescent labeling for molecular detection. © 2014 Elsevier B.V. All rights reserved.

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