130 research outputs found
Poly-Sarcosine and Poly(ethylene-glycol) interactions with proteins investigated using molecular dynamics simulations
Nanoparticles coated with hydrophilic polymers often show a reduction in
unspecific interactions with the biological environment, which improves their
biocompatibility. The molecular determinants of this reduction are not very
well understood yet, and their knowledge may help improving nanoparticle
design. Here we address, using molecular dynamics simulations, the interactions
of human serum albumin, the most abundant serum protein, with two promising
hydrophilic polymers used for the coating of therapeutic nanoparticles,
poly(ethylene-glycol) and poly-sarcosine. By simulating the protein immersed in
a polymer-water mixture, we show that the two polymers have a very similar
affinity for the protein surface, both in terms of the amount of polymer
adsorbed and also in terms of the type of amino acids mainly involved in the
interactions. We further analyze the kinetics of adsorption and how it affects
the polymer conformations. Minor differences between the polymers are observed
in the thickness of the adsorption layer, that are related to the different
degree of flexibility of the two molecules. In comparison poly-alanine, an
isomer of poly-sarcosine known to self-aggregate and induce protein
aggregation, shows a significantly larger affinity for the protein surface than
PEG and PSar, which we show to be related not to a different patterns of
interactions with the protein surface, but to the different way the polymer
interacts with water
Towards Automatic Identification of Elephants in the Wild
Identifying animals from a large group of possible individuals is very
important for biodiversity monitoring and especially for collecting data on a
small number of particularly interesting individuals, as these have to be
identified first before this can be done. Identifying them can be a very
time-consuming task. This is especially true, if the animals look very similar
and have only a small number of distinctive features, like elephants do. In
most cases the animals stay at one place only for a short period of time during
which the animal needs to be identified for knowing whether it is important to
collect new data on it. For this reason, a system supporting the researchers in
identifying elephants to speed up this process would be of great benefit. In
this paper, we present such a system for identifying elephants in the face of a
large number of individuals with only few training images per individual. For
that purpose, we combine object part localization, off-the-shelf CNN features,
and support vector machine classification to provide field researches with
proposals of possible individuals given new images of an elephant. The
performance of our system is demonstrated on a dataset comprising a total of
2078 images of 276 individual elephants, where we achieve 56% top-1 test
accuracy and 80% top-10 accuracy. To deal with occlusion, varying viewpoints,
and different poses present in the dataset, we furthermore enable the analysts
to provide the system with multiple images of the same elephant to be
identified and aggregate confidence values generated by the classifier. With
that, our system achieves a top-1 accuracy of 74% and a top-10 accuracy of 88%
on the held-out test dataset.Comment: Presented at the AI for Wildlife Conservation (AIWC) 2018 workshop in
Stockholm (https://sites.google.com/a/usc.edu/aiwc/home
How ill-defined constituents produce well-defined nanoparticles: Effect of polymer dispersity on the uniformity of copolymeric micelles
We investigate the effect of polymer length dispersity on the properties of
self-assembled micelles in solution by self-consistent field calculations.
Polydispersity stabilizes micelles by raising the free energy barriers of
micelle formation and dissolution. Most importantly, it significantly reduces
the size fluctuations of micelles: Block copolymers of moderate polydispersity
form more uniform particles than their monodisperse counterparts. We attribute
this to the fact that the packing of the solvophobic monomers in the core can
be optimized if the constituent polymers have different length.Comment: 4 main figures and 4 supplementary figures. Manuscript accepted for
publication in Physical Review Material
Bell-state measurement exceeding 50% success probability with linear optics
Bell-state projections serve as a fundamental basis for most quantum
communication and computing protocols today. However, with current Bell-state
measurement schemes based on linear optics, only two of four Bell states can be
identified, which means that the maximum success probability of this vital step
cannot exceed . Here, we experimentally demonstrate a scheme that amends
the original measurement with additional modes in the form of ancillary
photons, which leads to a more complex measurement pattern, and ultimately a
higher success probability of . Experimentally, we achieve a success
probability of , a significant improvement over the
conventional scheme. With the possibility of extending the protocol to a larger
number of ancillary photons, our work paves the way towards more efficient
realisations of quantum technologies based on Bell-state measurements
Trendbericht Makromolekulare Chemie
Biopolymere und biomedizinische Anwendung von Polymeren: Selbstorganisation DNA‐basierter Architekturen, mit denen sich komplexe Nanostrukturen herstellen lassen. Polymeranalytik: Superauflösungsfluoreszenzmikroskopie verrät die Vernetzungsstruktur von Mikrogelen und korreliert die Struktur mit den Eigenschaften. Polymerhybride und Kompositmaterialien: lokal kontrollierte Polymeranlagerung an Silicapartikeln. Synthesestrategien: lebende One‐Pot‐ Reaktionen, die chemische Funktionalitäten einbinden oder definierte Blockcopolymere liefern. Außerdem: mizellare photonische Kristalle
Efficient Shielding of Polyplexes Using Heterotelechelic Polysarcosines
Shielding agents are commonly used to shield polyelectrolyte complexes, e.g., polyplexes, from agglomeration and precipitation in complex media like blood, and thus enhance their in vivo circulation times. Since up to now primarily poly(ethylene glycol) (PEG) has been investigated to shield non-viral carriers for systemic delivery, we report on the use of polysarcosine (pSar) as a potential alternative for steric stabilization. A redox-sensitive, cationizable lipo-oligomer structure (containing two cholanic acids attached via a bioreducible disulfide linker to an oligoaminoamide backbone in T-shape configuration) was equipped with azide-functionality by solid phase supported synthesis. After mixing with small interfering RNA (siRNA), lipopolyplexes formed spontaneously and were further surface-functionalized with polysarcosines. Polysarcosine was synthesized by living controlled ring-opening polymerization using an azide-reactive dibenzo-aza-cyclooctyne-amine as an initiator. The shielding ability of the resulting formulations was investigated with biophysical assays and by near-infrared fluorescence bioimaging in mice. The modification of similar to 100 nm lipopolyplexes was only slightly increased upon functionalization. Cellular uptake into cells was strongly reduced by the pSar shielding. Moreover, polysarcosine-shielded polyplexes showed enhanced blood circulation times in bioimaging studies compared to unshielded polyplexes and similar to PEG-shielded polyplexes. Therefore, polysarcosine is a promising alternative for the shielding of non-viral, lipo-cationic polyplexes
Zebrafish embryos allow prediction of nanoparticle circulation times in mice and facilitate quantification of nanoparticle-cell interactions
The zebrafish embryo is a vertebrate well suited for visualizing nanoparticles at high resolution in live animals. Its optical transparency and genetic versatility allow noninvasive, real-time observations of vascular flow of nanoparticles and their interactions with cells throughout the body. As a consequence, this system enables the acquisition of quantitative data that are difficult to obtain in rodents. Until now, a few studies using the zebrafish model have only described semiquantitative results on key nanoparticle parameters. Here, a MACRO dedicated to automated quantitative methods is described for analyzing important parameters of nanoparticle behavior, such as circulation time and interactions with key target cells, macrophages, and endothelial cells. Direct comparison of four nanoparticle (NP) formulations in zebrafish embryos and mice reveals that data obtained in zebrafish can be used to predict NPs' behavior in the mouse model. NPs having long or short blood circulation in rodents behave similarly in the zebrafish embryo, with low circulation times being a consequence of NP uptake into macrophages or endothelial cells. It is proposed that the zebrafish embryo has the potential to become an important intermediate screening system for nanoparticle research to bridge the gap between cell culture studies and preclinical rodent models such as the mouse
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Myeloid Zinc Finger 1 (Mzf1) Differentially Modulates Murine Cardiogenesis by Interacting with an Nkx2.5 Cardiac Enhancer
Vertebrate heart development is strictly regulated by temporal and spatial expression of growth and transcription factors (TFs). We analyzed nine TFs, selected by in silico analysis of an Nkx2.5 enhancer, for their ability to transactivate the respective enhancer element that drives, specifically, expression of genes in cardiac progenitor cells (CPCs). Mzf1 showed significant activity in reporter assays and bound directly to the Nkx2.5 cardiac enhancer (Nkx2.5 CE) during murine ES cell differentiation. While Mzf1 is established as a hematopoietic TF, its ability to regulate cardiogenesis is completely unknown. Mzf1 expression was significantly enriched in CPCs from in vitro differentiated ES cells and in mouse embryonic hearts. To examine the effect of Mzf1 overexpression on CPC formation, we generated a double transgenic, inducible, tetOMzf1-Nkx2.5 CE eGFP ES line. During in vitro differentiation an early and continuous Mzf1 overexpression inhibited CPC formation and cardiac gene expression. A late Mzf1 overexpression, coincident with a second physiological peak of Mzf1 expression, resulted in enhanced cardiogenesis. These findings implicate a novel, temporal-specific role of Mzf1 in embryonic heart development. Thereby we add another piece of puzzle in understanding the complex mechanisms of vertebrate cardiac development and progenitor cell differentiation. Consequently, this knowledge will be of critical importance to guide efficient cardiac regenerative strategies and to gain further insights into the molecular basis of congenital heart malformations
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