Habits and Binds of Mathematics Education in the Anthropocen

<p>(a) A signaling network for cell death regulation [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0165049#pone.0165049.ref011" target="_blank">11</a>]. Cell death is enhanced due to DNA damage while inhibited by the signals transmitted from EGFR. The arrow shape represents activation while a flat-head edge means inhibition. Pink nodes denote the species that have experimental measurements. (b) The simulation results of DNA Damage and Cell Death.</p

Clearance Pathways and Tumor Targeting of Imaging Nanoparticles

A basic understanding of how imaging nanoparticles are removed from the normal organs/tissues but retained in the tumors is important for their future clinical applications in early cancer diagnosis and therapy. In this review, we discuss current understandings of clearance pathways and tumor targeting of small-molecule- and inorganic-nanoparticle-based imaging probes with an emphasis on molecular nanoprobes, a class of inorganic nanoprobes that can escape reticuloendothelial system (RES) uptake and be rapidly eliminated from the normal tissues/organs <i>via</i> kidneys but can still passively target the tumor with high efficiency through the enhanced permeability permeability and retention (EPR) effect. The impact of nanoparticle design (size, shape, and surface chemistry) on their excretion, pharmacokinetics, and passive tumor targeting were quantitatively discussed. Synergetic integration of effective renal clearance and EPR effect offers a promising pathway to design low-toxicity and high-contrast-enhancement imaging nanoparticles that could meet with the clinical translational requirements of regulatory agencies

Number of intra-peptide and inter-peptide salt bridges averaged from the last 5 ns MD simulations.

<p>Number of intra-peptide and inter-peptide salt bridges averaged from the last 5 ns MD simulations.</p

The most populated Aβ dimeric clusters extracted from the condensed areas of principle component analysis maps for (A) MWT0, (B) MWT90, (C) MWT170, (D) DWT25, (E) DWT265, and (F) DWT330.

<p>The most populated Aβ dimeric clusters extracted from the condensed areas of principle component analysis maps for (A) MWT0, (B) MWT90, (C) MWT170, (D) DWT25, (E) DWT265, and (F) DWT330.</p

Residue-residue interaction maps including sidechain contacts (<i>upper left triangular corner</i>) and hydrogen bonds (<i>lower right triangular corner</i>) for (A) MWT0, (B) MWT90, (C) MWT170, (D) MMT0, (E) DWT25, (F) DWT265, (G) DWT330, and (H) DMT25.

<p>A sidechain contact is defined if the center of mass of sidechains between two residues is less than 6.0 Å. A hydrogen bond is defined if donor-acceptor distance is <3.5 Å and accepter-donor-hydrogen angle is >120°.</p

Comparison of secondary structure populations between the initial 5 ns (<i>left column</i>) and final 5 ns (<i>right column</i>) conformations for six wild-types and two mutants of Aβ globulomers.

<p>Comparison of secondary structure populations between the initial 5 ns (<i>left column</i>) and final 5 ns (<i>right column</i>) conformations for six wild-types and two mutants of Aβ globulomers.</p

Comparison of solvent accessible surface area of hydrophobic C-terminal residues Ile31-Ala42, charged/hydrophilic N-terminal residues Leu17-Ser26, and turn residues Asn27-Ala30 between the initial 5 ns (<i>left column</i>) and the final 5 ns (<i>right column</i>) trajectories for all globulomers.

<p>Comparison of solvent accessible surface area of hydrophobic C-terminal residues Ile31-Ala42, charged/hydrophilic N-terminal residues Leu17-Ser26, and turn residues Asn27-Ala30 between the initial 5 ns (<i>left column</i>) and the final 5 ns (<i>right column</i>) trajectories for all globulomers.</p

A three-step assembly procedure for constructing Aβ_17–42 globulomers by using monomer or dimer building blocks.

<p>Step 1: Aβ monomer/dimer aligns parallel to the z axis (i.e. core axis) and then is rotated and replicated to form an annular structure. Step 2: each building block (i.e. monomer or dimer) is self-rotated along its β-strand axis at the center of mass by 5° interval from 0° to 360° to generate 72 candidates. Step 3: each candidate is energy minimized using GBSW implicit solvent model to obtain preliminary energy profiles of monomer-based globulomers (<i>red</i>) and dimer-based globulomers (<i>black</i>). Six lowest-energy globulomers with different peptide packings are preselected as initial conformations for subsequent explicit-solvent MD simulations to examine their structural stability.</p

Number of dimers formed in the Aβ globulomers during 40 ns MD simulations.

<p>Number of dimers formed in the Aβ globulomers during 40 ns MD simulations.</p

Energy decomposition for all globulomers averaged from the last 10 ns simulations.

<p>Energy decomposition for all globulomers averaged from the last 10 ns simulations.</p