10,468 research outputs found
Silver Nanoparticle Aggregates as Highly Efficient Plasmonic Antennas for Fluorescence Enhancement
The enhanced local fields around plasmonic structures can lead to enhancement of the excitation and modification of the emission quantum yield of fluorophores. So far, high enhancement of fluorescence intensity from dye molecules was demonstrated using bow-tie gap antenna made by e-beam lithography. However, the high manufacturing cost and the fact that currently there are no effective ways to place fluorophores only at the gap prevent the use of these structures for enhancing fluorescence-based biochemical assays. We report on the simultaneous modification of fluorescence intensity and lifetime of dye-labeled DNA in the presence of aggregated silver nanoparticles. The nanoparticle aggregates act as efficient plasmonic antennas, leading to more than 2 orders of magnitude enhancement of the average fluorescence. This is comparable to the best-reported fluorescence enhancement for a single molecule but here applies to the average signal detected from all fluorophores in the system. This highlights the remarkable efficiency of this system for surface-enhanced fluorescence. Moreover, we show that the fluorescence intensity enhancement varies with the plasmon resonance position and measure a significant reduction (300×) of the fluorescence lifetime. Both observations are shown to be in agreement with the electromagnetic model of surface-enhanced fluorescence
DNA-encoded nucleosome occupancy is associated with transcription levels in the human malaria parasite Plasmodium falciparum.
BackgroundIn eukaryotic organisms, packaging of DNA into nucleosomes controls gene expression by regulating access of the promoter to transcription factors. The human malaria parasite Plasmodium falciparum encodes relatively few transcription factors, while extensive nucleosome remodeling occurs during its replicative cycle in red blood cells. These observations point towards an important role of the nucleosome landscape in regulating gene expression. However, the relation between nucleosome positioning and transcriptional activity has thus far not been explored in detail in the parasite.ResultsHere, we analyzed nucleosome positioning in the asexual and sexual stages of the parasite's erythrocytic cycle using chromatin immunoprecipitation of MNase-digested chromatin, followed by next-generation sequencing. We observed a relatively open chromatin structure at the trophozoite and gametocyte stages, consistent with high levels of transcriptional activity in these stages. Nucleosome occupancy of genes and promoter regions were subsequently compared to steady-state mRNA expression levels. Transcript abundance showed a strong inverse correlation with nucleosome occupancy levels in promoter regions. In addition, AT-repeat sequences were strongly unfavorable for nucleosome binding in P. falciparum, and were overrepresented in promoters of highly expressed genes.ConclusionsThe connection between chromatin structure and gene expression in P. falciparum shares similarities with other eukaryotes. However, the remarkable nucleosome dynamics during the erythrocytic stages and the absence of a large variety of transcription factors may indicate that nucleosome binding and remodeling are critical regulators of transcript levels. Moreover, the strong dependency between chromatin structure and DNA sequence suggests that the P. falciparum genome may have been shaped by nucleosome binding preferences. Nucleosome remodeling mechanisms in this deadly parasite could thus provide potent novel anti-malarial targets
Identification of parameters in amplitude equations describing coupled wakes
We study the flow behind an array of equally spaced parallel cylinders. A
system of Stuart-Landau equations with complex parameters is used to model the
oscillating wakes. Our purpose is to identify the 6 scalar parameters which
most accurately reproduce the experimental data of Chauve and Le Gal [{Physica
D {\bf 58}}, pp 407--413, (1992)]. To do so, we perform a computational search
for the minimum of a distance \calj. We define \calj as the sum-square
difference of the data and amplitudes reconstructed using coupled equations.
The search algorithm is made more efficient through the use of a partially
analytical expression for the gradient . Indeed
can be obtained by the integration of a dynamical system propagating backwards
in time (a backpropagation equation for the Lagrange multipliers). Using the
parameters computed via the backpropagation method, the coupled Stuart-Landau
equations accurately predicted the experimental data from Chauve and Le Gal
over a correlation time of the system. Our method turns out to be quite robust
as evidenced by using noisy synthetic data obtained from integrations of the
coupled Stuart-Landau equations. However, a difficulty remains with
experimental data: in that case the several sets of identified parameters are
shown to yield equivalent predictions. This is due to a strong discretization
or ``round-off" error arising from the digitalization of the video images in
the experiment. This ambiguity in parameter identification has been reproduced
with synthetic data subjected to the same kind of discretization.Comment: 25 pages uuencoded compressed PostScript file (58K) with 13 figures
(155K in separated file) Submitted to Physica
Business Capability Models : current landscape and next steps for the EUNIS community
Publisher Copyright: © 2022, EasyChair. All rights reserved.This paper takes a policy perspective on the development and governance of Business Capability Models in Higher Education. In particular, we look at the next steps in international collaboration around the Higher Education Reference Model (HERM) launched in 2021. The motivation is to highlight the European challenges and contributions to this concept. To do so, the paper draws on insights from the EUNIS EA SIG community. The paper also argues that ongoing work in the domain of interoperability underscores the importance of a common framework such as HERM. At the same time, EUNIS can build upon those experiences when collaborating on the development of HERM. The main recommendation of the paper is that EUNIS in general and the EA SIG, in particular, should actively engage in the future development of HERM. More specifically, we see a need to focus on the implications of translating the model into the broader European context.Peer reviewe
Asymptotically optimal quantum channel reversal for qudit ensembles and multimode Gaussian states
We investigate the problem of optimally reversing the action of an arbitrary
quantum channel C which acts independently on each component of an ensemble of
n identically prepared d-dimensional quantum systems. In the limit of large
ensembles, we construct the optimal reversing channel R* which has to be
applied at the output ensemble state, to retrieve a smaller ensemble of m
systems prepared in the input state, with the highest possible rate m/n. The
solution is found by mapping the problem into the optimal reversal of Gaussian
channels on quantum-classical continuous variable systems, which is here solved
as well. Our general results can be readily applied to improve the
implementation of robust long-distance quantum communication. As an example, we
investigate the optimal reversal rate of phase flip channels acting on a
multi-qubit register.Comment: 17 pages, 3 figure
Complete analysis of the B-cell response to a protein antigen, from in vivo germinal centre formation to 3-D modelling of affinity maturation
Somatic hypermutation of immunoglobulin variable region genes occurs within germinal centres (GCs) and is the process responsible for affinity maturation of antibodies during an immune response. Previous studies have focused almost exclusively on the immune response to haptens, which may be unrepresentative of epitopes on protein antigens. In this study, we have exploited a model system that uses transgenic B and CD4<sup>+</sup> T cells specific for hen egg lysozyme (HEL) and a chicken ovalbumin peptide, respectively, to investigate a tightly synchronized immune response to protein antigens of widely differing affinities, thus allowing us to track many facets of the development of an antibody response at the antigen-specific B cell level in an integrated system <i>in</i> <i>vivo</i>. Somatic hypermutation of immunoglobulin variable genes was analysed in clones of transgenic B cells proliferating in individual GCs in response to HEL or the cross-reactive low-affinity antigen, duck egg lysozyme (DEL). Molecular modelling of the antibody–antigen interface demonstrates that recurring mutations in the antigen-binding site, selected in GCs, enhance interactions of the antibody with DEL. The effects of these mutations on affinity maturation are demonstrated by a shift of transgenic serum antibodies towards higher affinity for DEL in DEL-cOVA immunized mice. The results show that B cells with high affinity antigen receptors can revise their specificity by somatic hypermutation and antigen selection in response to a low-affinity, cross-reactive antigen. These observations shed further light on the nature of the immune response to pathogens and autoimmunity and demonstrate the utility of this novel model for studies of the mechanisms of somatic hypermutation
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Reassessment of the evolution of wheat chromosomes 4A, 5A, and 7B.
Key messageComparison of genome sequences of wild emmer wheat and Aegilops tauschii suggests a novel scenario of the evolution of rearranged wheat chromosomes 4A, 5A, and 7B. Past research suggested that wheat chromosome 4A was subjected to a reciprocal translocation T(4AL;5AL)1 that occurred in the diploid progenitor of the wheat A subgenome and to three major rearrangements that occurred in polyploid wheat: pericentric inversion Inv(4AS;4AL)1, paracentric inversion Inv(4AL;4AL)1, and reciprocal translocation T(4AL;7BS)1. Gene collinearity along the pseudomolecules of tetraploid wild emmer wheat (Triticum turgidum ssp. dicoccoides, subgenomes AABB) and diploid Aegilops tauschii (genomes DD) was employed to confirm these rearrangements and to analyze the breakpoints. The exchange of distal regions of chromosome arms 4AS and 4AL due to pericentric inversion Inv(4AS;4AL)1 was detected, and breakpoints were validated with an optical Bionano genome map. Both breakpoints contained satellite DNA. The breakpoints of reciprocal translocation T(4AL;7BS)1 were also found. However, the breakpoints that generated paracentric inversion Inv(4AL;4AL)1 appeared to be collocated with the 4AL breakpoints that had produced Inv(4AS;4AL)1 and T(4AL;7BS)1. Inv(4AS;4AL)1, Inv(4AL;4AL)1, and T(4AL;7BS)1 either originated sequentially, and Inv(4AL;4AL)1 was produced by recurrent chromosome breaks at the same breakpoints that generated Inv(4AS;4AL)1 and T(4AL;7BS)1, or Inv(4AS;4AL)1, Inv(4AL;4AL)1, and T(4AL;7BS)1 originated simultaneously. We prefer the latter hypothesis since it makes fewer assumptions about the sequence of events that produced these chromosome rearrangements
Fourier Magnetic Imaging with Nanoscale Resolution and Compressed Sensing Speed-up using Electronic Spins in Diamond
Optically-detected magnetic resonance using Nitrogen Vacancy (NV) color
centres in diamond is a leading modality for nanoscale magnetic field imaging,
as it provides single electron spin sensitivity, three-dimensional resolution
better than 1 nm, and applicability to a wide range of physical and biological
samples under ambient conditions. To date, however, NV-diamond magnetic imaging
has been performed using real space techniques, which are either limited by
optical diffraction to 250 nm resolution or require slow, point-by-point
scanning for nanoscale resolution, e.g., using an atomic force microscope,
magnetic tip, or super-resolution optical imaging. Here we introduce an
alternative technique of Fourier magnetic imaging using NV-diamond. In analogy
with conventional magnetic resonance imaging (MRI), we employ pulsed magnetic
field gradients to phase-encode spatial information on NV electronic spins in
wavenumber or k-space followed by a fast Fourier transform to yield real-space
images with nanoscale resolution, wide field-of-view (FOV), and compressed
sensing speed-up.Comment: 31 pages, 10 figure
Positive Outcomes of HAART at 24 Months in HIV-Infected Patients in Cambodia.
OBJECTIVES: African and Asian cohort studies have demonstrated the feasibility and efficacy of HAART in resource-poor settings. The long-term virological outcome and clinico-immunological criteria of success remain important questions. We report the outcomes at 24 months of antiretroviral therapy (ART) in patients treated in a Médecins Sans Frontières/Ministry of Health programme in Cambodia. METHODS: Adults who started HAART 24 +/- 2 months ago were included. Plasma HIV-RNA levels were assessed by real-time polymerase chain reaction. Factors associated with virological failure were analysed using logistic regression. RESULTS: Of 416 patients, 59.2% were men; the median age was 33.6 years. At baseline, 95.2% were ART naive, 48.9% were at WHO stage IV, and 41.6% had a body mass index less than 18 kg/m. The median CD4 cell count was 11 cells/microl. A stavudine-lamivudine-efavirenz-containing regimen was initiated predominantly (81.0%). At follow-up (median 23.8 months), 350 (84.1%) were still on HAART, 53 (12.7%) had died, six (1.4%) were transferred, and seven (1.7%) were lost to follow-up. Estimates of survival were 85.5% at 24 months. Of 346 tested patients, 259 (74.1%) had CD4 cell counts greater than 200 cells/microl and 306 (88.4%) had viral loads of less than 400 copies/ml. Factors associated with virological failure at 24 months were non-antiretroviral naive, an insufficient CD4 cell gain of less than 350 cells/microl or a low trough plasma ART concentration. In an intention-to-treat analysis, 73.6% of patients were successfully treated. CONCLUSION: Positive results after 2 years of advanced HIV further demonstrate the efficacy of HAART in the medium term in resource-limited settings
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