2,352 research outputs found
Exploring the Relationship between BODIPY Structure and Spectroscopic Properties to Design Fluorophores for Bioimaging
Designing chromophores for biological applications requires a fundamental understanding of how the chemical structure of a chromophore influences its photophysical properties. We here describe the synthesis of a library of BODIPY dyes, exploring diversity at various positions around the BODIPY core. The results show that the nature and position of substituents have a dramatic effect on the spectroscopic properties. Substituting in a heavy atom or adjusting the size and orientation of a conjugated system provides a means of altering the spectroscopic profiles with high precision. The insight from the structureâactivity relationship was applied to devise a new BODIPY dye with rationally designed photochemical properties including absorption towards the nearâinfrared region. The dye also exhibited switchâon fluorescence to enable visualisation of cells with high signalâtoânoise ratio without washingâout of unbound dye. The BODIPYâbased probe is nonâcytotoxic and compatible with staining procedures including cell fixation and immunofluorescence microscopy
Purification of Nanoparticles by Size and Shape
Producing monodisperse nanoparticles is essential to ensure consistency in biological experiments and to enable a smooth translation into the clinic. Purification of samples into discrete sizes and shapes may not only improve sample quality, but also provide us with the tools to understand which physical properties of nanoparticles are beneficial for a drug delivery vector. In this study, using polymersomes as a model system, we explore four techniques for purifying pre-formed nanoparticles into discrete fractions based on their size, shape or density. We show that these techniques can successfully separate polymersomes into monodisperse fractions
Rapamycin Combined with Anti-CD45RB mAb and IL-10 or with G-CSF Induces Tolerance in a Stringent Mouse Model of Islet Transplantation
Background: A large pool of preexisting alloreactive effector T cells can cause allogeneic graft rejection following transplantation. However, it is possible to induce transplant tolerance by altering the balance between effector and regulatory T (Treg) cells. Among the various Treg-cell types, Foxp3 +Treg and IL-10-producing T regulatory type 1 (Tr1) cells have frequently been associated with tolerance following transplantation in both mice and humans. Previously, we demonstrated that rapamycin+IL-10 promotes Tr1-cell-associated tolerance in Balb/c mice transplanted with C57BL/6 pancreatic islets. However, this same treatment was unsuccessful in C57BL/6 mice transplanted with Balb/c islets (classified as a stringent transplant model). We accordingly designed a protocol that would be effective in the latter transplant model by simultaneously depleting effector T cells and fostering production of Treg cells. We additionally developed and tested a clinically translatable protocol that used no depleting agent. Methodology/Principal Findings: Diabetic C57BL/6 mice were transplanted with Balb/c pancreatic islets. Recipient mice transiently treated with anti-CD45RB mAb+rapamycin+IL-10 developed antigen-specific tolerance. During treatment, Foxp3 +Treg cells were momentarily enriched in the blood, followed by accumulation in the graft and draining lymph node, whereas CD4 +IL-10 +IL-4 - T (i.e., Tr1) cells localized in the spleen. In long-term tolerant mice, only CD4 +IL-10 +IL-4 - T cells remained enriched in the spleen and IL-10 was key in the maintenance of tolerance. Alternatively, recipient mice were treated with two compounds routinely used in the clinic (namely, rapamycin and G-CSF); this drug combination promoted tolerance associated with CD4 +IL-10 +IL-4 - T cells. Conclusions/Significance: The anti-CD45RB mAb+rapamycin+IL-10 combined protocol promotes a state of tolerance that is IL-10 dependent. Moreover, the combination of rapamycin+G-CSF induces tolerance and such treatment could be readily translatable into the clinic. © 2011 Gagliani et al
Linking dwarf galaxies to halo building blocks with the most metal-poor star in Sculptor
Current cosmological models indicate that the Milky Way's stellar halo was
assembled from many smaller systems. Based on the apparent absence of the most
metal-poor stars in present-day dwarf galaxies, recent studies claimed that the
true Galactic building blocks must have been vastly different from the
surviving dwarfs. The discovery of an extremely iron-poor star (S1020549) in
the Sculptor dwarf galaxy based on a medium-resolution spectrum cast some doubt
on this conclusion. However, verification of the iron-deficiency and
measurements of additional elements, such as the alpha-element Mg, are
mandatory for demonstrating that the same type of stars produced the metals
found in dwarf galaxies and the Galactic halo. Only then can dwarf galaxy stars
be conclusively linked to early stellar halo assembly. Here we report
high-resolution spectroscopic abundances for 11 elements in S1020549,
confirming the iron abundance of less than 1/4000th that of the Sun, and
showing that the overall abundance pattern mirrors that seen in low-metallicity
halo stars, including the alpha-elements. Such chemical similarity indicates
that the systems destroyed to form the halo billions of years ago were not
fundamentally different from the progenitors of present-day dwarfs, and
suggests that the early chemical enrichment of all galaxies may be nearly
identical.Comment: 16 pages, including 2 figures. Accepted for publication in Nature. It
is embargoed for discussion in the press until formal publication in Natur
Diagnosing Spin at the LHC via Vector Boson Fusion
We propose a new technique for determining the spin of new massive particles
that might be discovered at the Large Hadron Collider. The method relies on
pair-production of the new particles in a kinematic regime where the vector
boson fusion production mechanism is enhanced. For this regime, we show that
the distribution of the leading jets as a function of their relative azimuthal
angle can be used to distinguish spin-0 from spin-1/2 particles. We illustrate
this effect by considering the particular cases of (i) strongly-interacting,
stable particles and (ii) supersymmetric particles carrying color charge. We
argue that this method should be applicable in a wide range of new physics
scenarios.Comment: 5 pages, 4 figure
Photon Management in Two-Dimensional Disordered Media
Elaborating reliable and versatile strategies for efficient light coupling
between free space and thin films is of crucial importance for new technologies
in energy efficiency. Nanostructured materials have opened unprecedented
opportunities for light management, notably in thin-film solar cells. Efficient
coherent light trapping has been accomplished through the careful design of
plasmonic nanoparticles and gratings, resonant dielectric particles and
photonic crystals. Alternative approaches have used randomly-textured surfaces
as strong light diffusers to benefit from their broadband and wide-angle
properties. Here, we propose a new strategy for photon management in thin films
that combines both advantages of an efficient trapping due to coherent optical
effects and broadband/wide-angle properties due to disorder. Our approach
consists in the excitation of electromagnetic modes formed by multiple light
scattering and wave interference in two-dimensional random media. We show, by
numerical calculations, that the spectral and angular responses of thin films
containing disordered photonic patterns are intimately related to the in-plane
light transport process and can be tuned through structural correlations. Our
findings, which are applicable to all waves, are particularly suited for
improving the absorption efficiency of thin-film solar cells and can provide a
novel approach for high-extraction efficiency light-emitting diodes
The HIV Tat protein affects processing of ribosomal RNA precursor
<p>Abstract</p> <p>Background</p> <p>Inside the cell, the HIV Tat protein is mainly found in the nucleus and nucleolus. The nucleolus, the site of ribosome biogenesis, is a highly organized, non-membrane-bound sub-compartment where proteins with a high affinity for nucleolar components are found. While it is well known that Tat accumulates in the nucleolus via a specific nucleolar targeting sequence, its function in this compartment it still unknown.</p> <p>Results</p> <p>To clarify the significance of the Tat nucleolar localization, we induced the expression of the protein during oogenesis in <it>Drosophila melanogaster </it>strain transgenic for HIV-<it>tat </it>gene. Here we show that Tat localizes in the nucleoli of <it>Drosophila </it>oocyte nurse cells, where it specifically co-localizes with fibrillarin. Tat expression is accompanied by a significant decrease of cytoplasmic ribosomes, which is apparently related to an impairment of ribosomal rRNA precursor processing. Such an event is accounted for by the interaction of Tat with fibrillarin and U3 snoRNA, which are both required for pre-rRNA maturation.</p> <p>Conclusion</p> <p>Our data contribute to understanding the function of Tat in the nucleolus, where ribosomal RNA synthesis and cell cycle control take place. The impairment of nucleolar pre-rRNA maturation through the interaction of Tat with fibrillarin-U3snoRNA complex suggests a process by which the virus modulates host response, thus contributing to apoptosis and protein shut-off in HIV-uninfected cells.</p
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Inflation and Dark Energy from spectroscopy at z > 2
The expansion of the Universe is understood to have accelerated during two
epochs: in its very first moments during a period of Inflation and much more
recently, at z < 1, when Dark Energy is hypothesized to drive cosmic
acceleration. The undiscovered mechanisms behind these two epochs represent
some of the most important open problems in fundamental physics. The large
cosmological volume at 2 < z < 5, together with the ability to efficiently
target high- galaxies with known techniques, enables large gains in the
study of Inflation and Dark Energy. A future spectroscopic survey can test the
Gaussianity of the initial conditions up to a factor of ~50 better than our
current bounds, crossing the crucial theoretical threshold of
of order unity that separates single field and
multi-field models. Simultaneously, it can measure the fraction of Dark Energy
at the percent level up to , thus serving as an unprecedented test of
the standard model and opening up a tremendous discovery space
The stellar halo of the Galaxy
Stellar halos may hold some of the best preserved fossils of the formation
history of galaxies. They are a natural product of the merging processes that
probably take place during the assembly of a galaxy, and hence may well be the
most ubiquitous component of galaxies, independently of their Hubble type. This
review focuses on our current understanding of the spatial structure, the
kinematics and chemistry of halo stars in the Milky Way. In recent years, we
have experienced a change in paradigm thanks to the discovery of large amounts
of substructure, especially in the outer halo. I discuss the implications of
the currently available observational constraints and fold them into several
possible formation scenarios. Unraveling the formation of the Galactic halo
will be possible in the near future through a combination of large wide field
photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes.
Full-resolution version available at
http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd
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