scholarly journals Metastable Regimes and Tipping Points of Biochemical Networks with Potential Applications in Precision Medicine

2019 ◽  
pp. 269-295 ◽  
Author(s):  
Satya Swarup Samal ◽  
Jeyashree Krishnan ◽  
Ali Hadizadeh Esfahani ◽  
Christoph Lüders ◽  
Andreas Weber ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Biochemical Networks ◽  
Tipping Points ◽  
Potential Applications

scholarly journals Synchrony and pattern formation of coupled genetic oscillators on a chip of artificial cells

2017 ◽  
Vol 114 (44) ◽  
pp. 11609-11614 ◽  
Author(s):  
Alexandra M. Tayar ◽  
Eyal Karzbrun ◽  
Vincent Noireaux ◽  
Roy H. Bar-Ziv
Keyword(s):  
Pattern Formation ◽  
Large Scale ◽  
Reaction Diffusion ◽  
Biochemical Networks ◽  
Artificial Cells ◽  
Diffusion Dynamics ◽  
Oscillatory Reactions ◽  
Potential Applications ◽  
On Chip ◽  
Genetic Oscillators

Understanding how biochemical networks lead to large-scale nonequilibrium self-organization and pattern formation in life is a major challenge, with important implications for the design of programmable synthetic systems. Here, we assembled cell-free genetic oscillators in a spatially distributed system of on-chip DNA compartments as artificial cells, and measured reaction–diffusion dynamics at the single-cell level up to the multicell scale. Using a cell-free gene network we programmed molecular interactions that control the frequency of oscillations, population variability, and dynamical stability. We observed frequency entrainment, synchronized oscillatory reactions and pattern formation in space, as manifestation of collective behavior. The transition to synchrony occurs as the local coupling between compartments strengthens. Spatiotemporal oscillations are induced either by a concentration gradient of a diffusible signal, or by spontaneous symmetry breaking close to a transition from oscillatory to nonoscillatory dynamics. This work offers design principles for programmable biochemical reactions with potential applications to autonomous sensing, distributed computing, and biomedical diagnostics.

scholarly journals Metastable regimes and tipping points of biochemical networks with potential applications in precision medicine

2018 ◽  
Author(s):  
Satya Swarup Samal ◽  
Jeyashree Krishnan ◽  
Ali Hadizadeh Esfahani ◽  
Christoph Lüders ◽  
Andreas Weber ◽  
...  
Keyword(s):  
Invariant Manifolds ◽  
Tropical Geometry ◽  
Cell Types ◽  
Biochemical Networks ◽  
Model Parameters ◽  
Tipping Points ◽  
Cancer Disease ◽  
Cell Alterations ◽  
Low Dimensional ◽  
Sensitive Parameters

AbstractThe concept of attractor of dynamic biochemical networks has been used to explain cell types and cell alterations in health and disease. We have recently proposed an extension of the notion of attractor to take into account metastable regimes, defined as long lived dynamical states of the network. These regimes correspond to slow dynamics on low dimensional invariant manifolds of the biochemical networks. Methods based on tropical geometry allow to compute the metastable regimes and represent them as polyhedra in the space of logarithms of the species concentrations. We are looking for sensitive parameters and tipping points of the networks by analyzing how these polyhedra depend on the model parameters. Using the coupled MAPK and PI3K/Akt signaling networks as an example, we test the idea that large changes of the metastable states can be associated to cancer disease specific alterations of the network. In particular, we show that for model parameters representing protein concentrations, the protein differential level between tumors of different types is reasonably reflected in the sensitivity scores, with sensitive parameters corresponding to differential proteins.

DNA damage assessment and potential applications in laboratory diagnostics and precision medicine

2018 ◽  
Vol 3 ◽  
pp. 31-31 ◽  
Author(s):  
Annika Reddig ◽  
Claudia E. Rübe ◽  
Stefan Rödiger ◽  
Peter Schierack ◽  
Dirk Reinhold ◽  
...  
Keyword(s):  
Dna Damage ◽  
Precision Medicine ◽  
Damage Assessment ◽  
Laboratory Diagnostics ◽  
Potential Applications

scholarly journals Sepsis Biomarkers

2019 ◽  
Vol 08 (01) ◽  
pp. 011-016 ◽  
Author(s):  
Hector Wong
Keyword(s):  
At Risk ◽  
Precision Medicine ◽  
Systemic Inflammation ◽  
Poor Outcome ◽  
Potential Applications ◽  
Diagnostic Applications

AbstractSepsis-related biomarkers have a variety of potential applications. The most well-known application is to differentiate patients with signs of systemic inflammation caused by infection, from those with systemic inflammation due to a non-infectious cause. This application is important for timely and judicious prescription of antibiotics. Apart from diagnostic applications, biomarkers can also be used to identify patients with sepsis who are at risk for poor outcome and to subgroup patients with sepsis based on biological commonalities. The latter two applications embody the concepts of prognostic and predictive enrichment, which are fundamental to precision medicine. This review will elaborate on these concepts, provide relevant examples, and discuss important considerations in the process of biomarkers discovery and development.

scholarly journals Approaching Sites of Action of Temozolomide for Pharmacological and Clinical Studies in Glioblastoma

Biomedicines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 1
Author(s):  
Margaux Fresnais ◽  
Sevin Turcan ◽  
Dirk Theile ◽  
Johannes Ungermann ◽  
Yasmin Abou Zeed ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Mode Of Action ◽  
Standard Of Care ◽  
Biological Action ◽  
Mass Spectrometric ◽  
Spectrometric Analysis ◽  
Therapeutic Approaches ◽  
Potential Applications ◽  
Sites Of Action ◽  
Novel Therapeutic

Temozolomide (TMZ), together with bulk resection and focal radiotherapy, is currently a standard of care for glioblastoma. Absorption, distribution, metabolism, and excretion (ADME) parameters, together with the mode of action of TMZ, make its biochemical and biological action difficult to understand. Accurate understanding of the mode of action of TMZ and the monitoring of TMZ at its anatomical, cellular, and molecular sites of action (SOAs) would greatly benefit precision medicine and the development of novel therapeutic approaches in combination with TMZ. In the present perspective article, we summarize the known ADME parameters and modes of action of TMZ, and we review the possible methodological options to monitor TMZ at its SOAs. We focus our descriptions of methodologies on mass spectrometry-based approaches, and all related considerations are taken into account regarding the avoidance of artifacts in mass spectrometric analysis during sampling, sample preparation, and the evaluation of results. Finally, we provide an overview of potential applications for precision medicine and drug development.

An in situ and ex situ TEM study of the formation of thin cobalt silicide films by molecular beam epitaxy on the silicon (100) surface

1988 ◽  
Vol 46 ◽  
pp. 884-885
Author(s):  
D. Loretto ◽  
J. M. Gibson ◽  
S. M. Yalisove ◽  
R. T. Tung
Keyword(s):  
Molecular Beam Epitaxy ◽  
Molecular Beam ◽  
Defect Density ◽  
High Vacuum ◽  
Ultra High Vacuum ◽  
Ex Situ ◽  
Metal Base ◽  
In Situ Experiments ◽  
Potential Applications

The cobalt disilicide/silicon system has potential applications as a metal-base and as a permeable-base transistor. Although thin, low defect density, films of CoSi2 on Si(111) have been successfully grown, there are reasons to believe that Si(100)/CoSi2 may be better suited to the transmission of electrons at the silicon/silicide interface than Si(111)/CoSi2. A TEM study of the formation of CoSi2 on Si(100) is therefore being conducted. We have previously reported TEM observations on Si(111)/CoSi2 grown both in situ, in an ultra high vacuum (UHV) TEM and ex situ, in a conventional Molecular Beam Epitaxy system.The procedures used for the MBE growth have been described elsewhere. In situ experiments were performed in a JEOL 200CX electron microscope, extensively modified to give a vacuum of better than 10-9 T in the specimen region and the capacity to do in situ sample heating and deposition. Cobalt was deposited onto clean Si(100) samples by thermal evaporation from cobalt-coated Ta filaments.

Microstructure of laser-irradiated, conducting Kapton polyimide

1995 ◽  
Vol 53 ◽  
pp. 502-503
Author(s):  
D. L. Callahan ◽  
Z. Ball ◽  
H. M. Phillips ◽  
R. Sauerbrey
Keyword(s):  
Electron Microscopy ◽  
Phase Transition ◽  
Transmission Electron Microscopy ◽  
Cross Section ◽  
Film Surface ◽  
Cross Sectional ◽  
General Utility ◽  
Transmission Electron ◽  
Considerable Debate ◽  
Potential Applications

Ultraviolet laser-irradiation can be used to induce an insulator-to-conductor phase transition on the surface of Kapton polyimide. Such structures have potential applications as resistors or conductors for VLSI applications as well as general utility electrodes. Although the percolative nature of the phase transformation has been well-established, there has been little definitive work on the mechanism or extent of transformation. In particular, there has been considerable debate about whether or not the transition is primarily photothermal in nature, as we propose, or photochemical. In this study, cross-sectional optical microscopy and transmission electron microscopy are utilized to characterize the nature of microstructural changes associated with the laser-induced pyrolysis of polyimide.Laser-modified polyimide samples initially 12 μm thick were prepared in cross-section by standard ultramicrotomy. Resulting contraction in parallel to the film surface has led to distortions in apparent magnification. The scale bars shown are calibrated for the direction normal to the film surface only.

Fabrication and characterization - by High Resolution Electron Microscopy and atom probe microanalysis - of Co-based metallic multilayer films

1990 ◽  
Vol 48 (4) ◽  
pp. 772-773
Author(s):  
Amanda K. Petford-Long ◽  
A. Cerezo ◽  
M.G. Hetherington
Keyword(s):  
Electron Microscopy ◽  
High Resolution ◽  
High Resolution Electron Microscopy ◽  
Atom Probe ◽  
Multilayer Films ◽  
Interface Roughness ◽  
Probe Field ◽  
Resolution Electron ◽  
Potential Applications ◽  
Field Ion Microscope

The fabrication of multilayer films (MLF) with layer thicknesses down to one monolayer has led to the development of materials with unique properties not found in bulk materials. The properties of interest depend critically on the structure and composition of the films, with the interfacial regions between the layers being of particular importance. There are a number of magnetic MLF systems based on Co, several of which have potential applications as perpendicular magnetic (e.g Co/Cr) or magneto-optic (e.g. Co/Pt) recording media. Of particular concern are the effects of parameters such as crystallographic texture and interface roughness, which are determined by the fabrication conditions, on magnetic properties and structure.In this study we have fabricated Co-based MLF by UHV thermal evaporation in the prechamber of an atom probe field-ion microscope (AP). The multilayers were deposited simultaneously onto cobalt field-ion specimens (for AP and position-sensitive atom probe (POSAP) microanalysis without exposure to atmosphere) and onto the flat (001) surface of oxidised silicon wafers (for subsequent study in cross-section using high-resolution electron microscopy (HREM) in a JEOL 4000EX. Deposi-tion was from W filaments loaded with material in the form of wire (Co, Fe, Ni, Pt and Au) or flakes (Cr). The base pressure in the chamber was around 8×10−8 torr during deposition with a typical deposition rate of 0.05 - 0.2nm/s.

Progress and perspectives on halide lithium conductors for all-solid-state lithium batteries

2020 ◽  
Vol 13 (5) ◽  
pp. 1429-1461 ◽  
Author(s):  
Xiaona Li ◽  
Jianwen Liang ◽  
Xiaofei Yang ◽  
Keegan R. Adair ◽  
Changhong Wang ◽  
...  
Keyword(s):  
Energy Storage ◽  
Solid State ◽  
Lithium Batteries ◽  
Electrochemical Stability ◽  
Superionic Conductors ◽  
Fundamental Understanding ◽  
Potential Applications ◽  
Synthesis Routes

This review focuses on fundamental understanding, various synthesis routes, chemical/electrochemical stability of halide-based lithium superionic conductors, and their potential applications in energy storage as well as related challenges.

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