2,681 research outputs found
Accelerating Monte Carlo simulations with an NVIDIA® graphics processor
Modern graphics cards, commonly used in desktop computers, have evolved beyond a simple interface between processor and display to incorporate sophisticated calculation engines that can be applied to general purpose computing. The Monte Carlo algorithm for modelling photon transport in turbid media has been implemented on an NVIDIA® 8800gt graphics card using the CUDA toolkit. The Monte Carlo method relies on following the trajectory of millions of photons through the sample, often taking hours or days to complete. The graphics-processor implementation, processing roughly 110 million scattering events per second, was found to run more than 70 times faster than a similar, single-threaded implementation on a 2.67 GHz desktop computer
Stages of neuronal network formation
Graph theoretical approaches have become a powerful tool for
investigating the architecture and dynamics of complex networks. The topology
of network graphs revealed small-world properties for very different real
systems among these neuronal networks. In this study, we observed the early
development of mouse retinal ganglion cell (RGC) networks in vitro using timelapse
video microscopy. By means of a time-resolved graph theoretical analysis
of the connectivity, shortest path length and the edge length, we were able to
discover the different stages during the network formation. Starting from single
cells, at the first stage neurons connected to each other ending up in a network
with maximum complexity. In the further course, we observed a simplification of
the network which manifested in a change of relevant network parameters such
as the minimization of the path length. Moreover, we found that RGC networks
self-organized as small-world networks at both stages; however, the optimization
occurred only in the second stage
Ligand Mediated Sequestering of Integrins in Raft-Mimicking Lipid Mixtures: The Role of Bilayer Asymmetry and Cholesterol Content
poster abstractLipid microdomains play an important functional role in plasma membranes. However, the small size and
transient nature of lipid/membrane heterogeneities in the plasma membrane make characterization of
microdomains and microdomain-related membrane processes quite challenging. To address this issue, we
recently introduced a powerful model membrane system that allows the investigation of membrane
protein sequestering and oligomerization in raft-mimicking lipid mixtures using combined confocal
fluorescence spectroscopy, photon counting histogram (PCH), and epifluorescence microscopy. Our
experiments on bilayer-spanning domains showed that αvβ3 and α5β1 integrins predominantly exist as
monomers and sequester preferentially to the liquid-disordered (ld) phase in the absence of ligands.
Notably, addition of vitronectin (αvβ3) and fibronectin (α5β1) caused substantial translocations of integrins
into the liquid-ordered (lo) phase without altering receptor oligomerization state. Here we expand our
previous studies and report on the sequestering and oligomerization state of αvβ3 and α5β1 in asymmetric
bilayer compositions containing coexisting lo and ld phases located exclusively in the top leaflet of the
bilayer (bottom leaflet shows only ld phase). Remarkably, in such a membrane environment, both
integrins show a higher affinity for the top leaflet-restricted lo domains in the absence of their respective
ligands. A slight change in the integrin sequestration was observed after addition of their respective
ligands. We also present experimental findings, which show that cholesterol content has a substantial
influence on integrin sequestering and oligomerization in raft-mimicking lipid mixtures. The described
experimental results highlight the potential importance of membrane asymmetry and lipid composition in
the sequestering of membrane proteins in biological membranes
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Nonspherical Nanoparticle Shape Stability Is Affected by Complex Manufacturing Aspects: Its Implications for Drug Delivery and Targeting
The shape of nanoparticles is known recently as an important design parameter influencing considerably the fate of nanoparticles with and in biological systems. Several manufacturing techniques to generate nonspherical nanoparticles as well as studies on in vitro and in vivo effects thereof have been described. However, nonspherical nanoparticle shape stability in physiological-related conditions and the impact of formulation parameters on nonspherical nanoparticle resistance still need to be investigated. To address these issues, different nanoparticle fabrication methods using biodegradable polymers are explored to produce nonspherical nanoparticles via the prevailing film-stretching method. In addition, systematic comparisons to other nanoparticle systems prepared by different manufacturing techniques and less biodegradable materials (but still commonly utilized for drug delivery and targeting) are conducted. The study evinces that the strong interplay from multiple nanoparticle properties (i.e., internal structure, Young's modulus, surface roughness, liquefaction temperature [glass transition (Tg) or melting (Tm)], porosity, and surface hydrophobicity) is present. It is not possible to predict the nonsphericity longevity by merely one or two factor(s). The most influential features in preserving the nonsphericity of nanoparticles are existence of internal structure and low surface hydrophobicity (i.e., surface-free energy (SFE) > ≈55 mN m−1, material–water interfacial tension 10 nm), porous (>1 m2 g−1), and in possession of low bulk liquefaction temperature (<100 °C). Interestingly, low surface hydrophobicity of nanoparticles can be obtained indirectly by the significant presence of residual stabilizers. Therefore, it is strongly suggested that nonsphericity of particle systems is highly dependent on surface chemistry but cannot be appraised separately from other factors. These results and reviews allot valuable guidelines for the design and manufacturing of nonspherical nanoparticles having adequate shape stability, thereby appropriate with their usage purposes. Furthermore, they can assist in understanding and explaining the possible mechanisms of nonspherical nanoparticles effectivity loss and distinctive material behavior at the nanoscale. © 2019 The Authors. Published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinhei
Neural coding of image structure and contrast polarity of Cartesian, hyperbolic and polar gratings in the primary and secondary visual cortex of the tree shrew
We comprehensively characterize spiking and visual evoked potential (VEP) activity in tree shrew V1 and V2 using Cartesian, hyperbolic and polar gratings. Neural selectivity to structure of Cartesian gratings was higher than other grating classes in both visual areas. From V1 to V2, structure selectivity of spiking activity increased, while corresponding VEP values tended to decrease, suggesting that single neuron coding of Cartesian grating attributes improved while the cortical columnar organization of these neurons became less precise from V1 to V2. We observed that neurons in V2 generally exhibited similar selectivity for polar and Cartesian gratings, suggesting that structure of polar-like stimuli might be encoded as early as in V2. This hypothesis is supported by the preference shift from V1 to V2 toward polar gratings of higher spatial frequency, consistent with the notion that V2 neurons encode visual scene borders and contours. Neural sensitivity to modulations of polarity of hyperbolic gratings was highest among all grating classes and closely related to the visual receptive field (RF) organization of ON- and OFF- dominated subregions. We show that spatial RF reconstructions depend strongly on grating class, suggesting that intracortical contributions to RF structure are strongest for Cartesian and polar gratings. Hyperbolic gratings tend to recruit least cortical elaboration such that the RF maps are similar to those generated by sparse noise, which most closely approximate feed-forward inputs. Our findings complement previous literature in primates, rodents and carnivores and highlight novel aspects of shape representation and coding occurring in mammalian early visual cortex
Effects of UV-B and water deficit on aroma precursors in grapes and flavor release during wine micro-vinification and consumption
UV-B radiation and water availability can affect amino acids(AAs) concentration in berries, resulting in the evolution of aroma compounds during alcoholic fermentation. This study investigated the effects of UV-B exposure and water availability on wine aroma compounds in Pinot noir, focusing on the role of AAs in the process.Enhanced UV-B radiation significantly decreased total AA concentrations and most individual AAs in berries and wines, while water deficit increased some individual AAs in wines. Higher alcohols, fatty acids, esters, monoterpenes, and C₁₃-norisoprenoids were affected by UV-B interaction with water deficit in wines. These results suggested individual or combined UV-B exposure and water deficit had direct effects on fruit AAs, leading to significant differences in some wine aroma compounds
Conjugates of Superoxide Dismutase 1 with Amphiphilic Poly(2-oxazoline) Block Copolymers for Enhanced Brain Delivery: Synthesis, Characterization and Evaluation in Vitro and in Vivo
Superoxide dismutase 1 (SOD1) efficiently catalyzes dismutation of superoxide but its poor delivery to the target sites in the body, such as brain, hinders its use as a therapeutic agent for superoxide-associated disorders. Here to enhance the delivery of SOD1 across the blood brain barrier (BBB) and in neurons the enzyme was conjugated with poly(2-oxazoline) (POx) block copolymers, P(MeOx-b-BuOx) or P(EtOx-b-BuOx), comprised of 1) hydrophilic 2-methyl-2-oxazoline (MeOx) or 2-ethyl-2-oxazoline (EtOx) and 2) hydrophobic 2-butyl-2-oxazoline (BuOx) repeating units. The conjugates contained from 2 to 3 POx chains joining the protein amino groups via cleavable -(ss)- or non-cleavable –(cc)- linkers at the BuOx block terminus. They retained 30% to 50% of initial SOD1 activity, were conformationally and thermally stable and assembled in 8 or 20 nm aggregates in aqueous solution. They had little if any toxicity to CATH.a neurons and displayed enhanced uptake in these neurons as compared to native or PEGylated SOD1. Of the two conjugates, SOD1-(cc)-P(MeOx-b-BuOx) and SOD1-(cc)-P(EtOx-b-BuOx) compared, the latter was entering cells 4 to 7 times faster and at 6 h colocalized predominantly with endoplasmic reticulum (41 ± 3%) and mitochondria (21 ± 2%). Colocalization with endocytosis markers and pathway inhibition assays suggested that it was internalized through lipid raft/caveolae, also employed by the P(EtOx-b-BuOx) copolymer. The SOD activity in cell lysates and ability to attenuate angiotensin II (Ang II)-induced superoxide in live cells were increased for this conjugate compared to SOD1 and PEG-SOD1. Studies in mice showed that SOD1-POx had ca. 1.75 times longer half-life in blood than native SOD1 (28.4 vs 15.9 min) and after i.v. administration penetrated the BBB significantly faster than albumin to accumulate in brain parenchyma. The conjugate maintained high stability both in serum and in brain (77% vs. 84% at 1 h post injection). Its amount taken up by the brain reached a maximum value of 0.08%ID/g (percent of the injected dose taken up per gram of brain) 4 h post injection. The entry of SOD1-(cc)-P(EtOx-b-BuOx) to the brain was mediated by a non-saturable mechanism. Altogether, SOD1-POx conjugates are promising candidates as macromolecular antioxidant therapies for superoxide-associated diseases such as Ang II induced neuro-cardiovascular diseases
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Polymer brushes on graphitic carbon nitride for patterning and as a SERS active sensing layer via incorporated nanoparticles
Graphitic carbon nitride (gCN) has a broad range of promising applications, from energy harvesting and storage to sensing. However, most of the applications are still restricted due to gCN poor dispersibility and limited functional groups. Herein, a direct photografting of gCN using various polymer brushes with tailorable functionalities via UV photopolymerization at ambient conditions is demonstrated. The systematic study of polymer brush-functionalized gCN reveals that the polymerization did not alter the inherent structure of gCN. Compared to the pristine gCN, the gCN-polymer composites show good dispersibility in various solvents such as water, ethanol, and tetrahydrofuran (THF). Patterned polymer brushes on gCN can be realized by employing photomask and microcontact printing technology. The polymer brushes with incorporated silver nanoparticles (AgNPs) on gCN can act as a multifunctional recyclable active sensing layer for surface-enhanced Raman spectroscopy (SERS) detection and photocatalysis. This multifunctionality is shown in consecutive cycles of SERS and photocatalytic degradation processes that can be applied to in situ monitor pollutants, such as dyes or pharmaceutical waste, with high chemical sensitivity as well as to water remediation. This dual functionality provides a significant advantage to our AgNPs/polymer-gCN with regard to state-of-the-art systems reported so far that only allow SERS pollutant detection but not their decomposition. These results may provide a new methodology for the covalent functionalization of gCN and may enable new applications in the field of catalysis, biosensors, and, most interestingly, environmental remediation
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Polymerization driven monomer passage through monolayer chemical vapour deposition graphene
Mass transport through graphene is receiving increasing attention due to the potential for molecular sieving. Experimental studies are mostly limited to the translocation of protons, ions, and water molecules, and results for larger molecules through graphene are rare. Here, we perform controlled radical polymerization with surface-anchored self-assembled initiator monolayer in a monomer solution with single-layer graphene separating the initiator from the monomer. We demonstrate that neutral monomers are able to pass through the graphene (via native defects) and increase the graphene defects ratio (Raman ID/IG) from ca. 0.09 to 0.22. The translocations of anionic and cationic monomers through graphene are significantly slower due to chemical interactions of monomers with the graphene defects. Interestingly, if micropatterned initiator-monolayers are used, the translocations of anionic monomers apparently cut the graphene sheet into congruent microscopic structures. The varied interactions between monomers and graphene defects are further investigated by quantum molecular dynamics simulations
Individualized targeted treatment in a case of a rare TFG::ROS1 fusion positive inflammatory myofibroblastic tumor (IMT)
Background
Inflammatory myofibroblastic tumor (IMTs) are rare mesenchymal neoplasms with slow growth. Resection is considered as therapeutic standard, with chemotherapy being insufficiently effective in advanced disease. ALK translocations are present in 50% of cases, ROS1 fusions (YWHAE::ROS1, TFG::ROS1) are extremely rare. Here, we present a case with TFG::ROS1 fusion and highlight the significance of molecular tumor boards (MTBs) in clinical precision oncology for post-last-line therapy.
Case Presentation
A 32-year-old woman presented with IMT diagnosed at age 27 for biopsy and treatment evaluation. Previous treatments included multiple resections and systemic therapy with vinblastine, cyclophosphamide, and methotrexate. A computed tomography scan showed extensive tumor infiltration of the psoas muscles and the posterior abdomen. Next generation sequencing revealed an actionable ROS1 fusion (TFG::ROS1) with breakpoints at exon 4/35 including the kinase domain and activating the RAS-pathway. TFG, the Trk-fused gene, exerts functions such as intracellular trafficking and exhibits high sequence homology between species. Based on single reports about efficacy of ROS1-targeting in ROS1 translocation positive IMTs the patient was started on crizotinib, an ATP-competitive small molecule c-MET, ALK and ROS1-inhibitor. With a follow-up of more than 9 months, the patient continues to show a profound response with major tumor regression, improved quality of life and no evidence for severe adverse events.
Conclusion
This case underscores the importance of the availability of modern molecular diagnostics and interdisciplinarity in precision oncology to identify rare, disease-defining genotypes that make an otherwise difficult-to-treat disease targetable
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