1,304 research outputs found
Momentum dependence in the dynamically assisted Sauter-Schwinger effect
Recently it has been found that the superposition of a strong and slow
electric field with a weaker and faster pulse can significantly enhance the
probability for non-perturbative electron-positron pair creation out of the
vacuum -- the dynamically assisted Sauter-Schwinger effect. Via the WKB method,
we estimate the momentum dependence of the pair creation probability and
compare it to existing numerical results. Besides the theoretical interest, a
better understanding of this pair creation mechanism should be helpful for the
planned experiments aiming at its detection.Comment: 4 pages RevTeX, 1 figur
Polyubiquitin chain assembly and organization determine the dynamics of protein activation and degradation
Protein degradation via ubiquitination is a major proteolytic mechanism in cells. Once a protein is destined for degradation, it is tagged by multiple ubiquitin (Ub) molecules. The synthesized polyubiquitin chains can be recognized by the 26S proteosome where proteins are degraded. These chains form through multiple ubiquitination cycles that are similar to multi-site phosphorylation cycles. As kinases and phosphatases, two opposing enzymes (E3 ligases and deubiquitinases DUBs) catalyze (de)ubiquitination cycles. Although multi-ubiquitination cycles are fundamental mechanisms of controlling protein concentrations within a cell, their dynamics have never been explored. Here, we fill this knowledge gap. We show that under permissive physiological conditions, the formation of polyubiquitin chain of length greater than two and subsequent degradation of the ubiquitinated protein, which is balanced by protein synthesis, can display bistable, switch-like responses. Interestingly, the occurrence of bistability becomes pronounced, as the chain grows, giving rise to “all-or-none” regulation at the protein levels. We give predictions of protein distributions under bistable regime awaiting experimental verification. Importantly, we show for the first time that sustained oscillations can robustly arise in the process of formation of ubiquitin chain, largely due to the degradation of the target protein. This new feature is opposite to the properties of multi-site phosphorylation cycles, which are incapable of generating oscillation if the total abundance of interconverted protein forms is conserved. We derive structural and kinetic constraints for the emergence of oscillations, indicating that a competition between different substrate forms and the E3 and DUB is critical for oscillation. Our work provides the first detailed elucidation of the dynamical features brought about by different molecular setups of the polyubiquitin chain assembly process responsible for protein degradation
Heat shock-induced phosphorylation of TAR DNA-binding protein 43 (TDP-43) by MAPK/ERK kinase regulates TDP-43 function
TAR DNA-binding protein (TDP-43) is a highly conserved and essential DNA- and RNA-binding protein that controls gene expression through RNA processing, in particular, regulation of splicing. Intracellular aggregation of TDP-43 is a hallmark of amyotrophic lateral sclerosis and ubiquitin-positive frontotemporal lobar degeneration. This TDP-43 pathology is also present in other types of neurodegeneration including Alzheimer's disease. We report here that TDP-43 is a substrate of MEK, a central kinase in the MAPK/ERK signaling pathway. TDP-43 dual phosphorylation by MEK, at threonine 153 and tyrosine 155 (p-T153/Y155), was dramatically increased by the heat shock response (HSR) in human cells. HSR promotes cell survival under proteotoxic conditions by maintaining protein homeostasis and preventing protein misfolding. MEK is activated by HSR and contributes to the regulation of proteome stability. Phosphorylated TDP-43 was not associated with TDP-43 aggregation, and p-T153/Y155 remained soluble under conditions that promote protein misfolding. We found that active MEK significantly alters TDP-43-regulated splicing and that phosphomimetic substitutions at these two residues reduce binding to GU-rich RNA. Cellular imaging using a phospho-specific p-T153/Y155 antibody showed that phosphorylated TDP-43 was specifically recruited to the nucleoli, suggesting that p-T153/Y155 regulates a previously unappreciated function of TDP-43 in the processing of nucleolar-associated RNA. These findings highlight a new mechanism that regulates TDP-43 function and homeostasis through phosphorylation and, therefore, may contribute to the development of strategies to prevent TDP-43 aggregation and to uncover previously unexplored roles of TDP-43 in cell metabolism
The distance to a star forming region in the Outer arm of the Galaxy
We performed astrometric observations with the VLBA of WB89-437, an H2O maser
source in the Outer spiral arm of the Galaxy. We measure an annual parallax of
0.167 +/- 0.006 mas, corresponding to a heliocentric distance of 6.0 +/- 0.2
kpc or a Galactocentric distance of 13.4 +/- 0.2 kpc. This value for the
heliocentric distance is considerably smaller than the kinematic distance of
8.6 kpc. This confirms the presence of a faint Outer arm toward l = 135
degrees. We also measured the full space motion of the object and find a large
peculiar motion of ~20 km/s toward the Galactic center. This peculiar motion
explains the large error in the kinematic distance estimate. We also find that
WB89-437 has the same rotation speed as the LSR, providing more evidence for a
flat rotation curve and thus the presence of dark matter in the outer Galaxy.Comment: The Astrophysical Journal, accepted, 16 pages, 4 Figure
Expansion of the ligand knowledge base for chelating P,P-donor ligands (LKB-PP)
[Image: see text] We have expanded the ligand knowledge base for bidentate P,P- and P,N-donor ligands (LKB-PP, Organometallics2008, 27, 1372–1383) by 208 ligands and introduced an additional steric descriptor (nHe(8)). This expanded knowledge base now captures information on 334 bidentate ligands and has been processed with principal component analysis (PCA) of the descriptors to produce a detailed map of bidentate ligand space, which better captures ligand variation and has been used for the analysis of ligand properties
Monitoring ethnic minorities in the Netherlands
Item does not contain fulltextThe article first summarises the history of ethnic minority policy in the Netherlands and the development of the ‘ethnic minority’ and ‘allochthonous’ categories, which are peculiar in comparative perspective in emphasising socio-economic disadvantage as a constitutive dimension of minority status and in setting the minority question within the broader Dutch political principle of ‘pillarisation’. The article then examines the use of statistics in public policy, in a context where the national census has been discontinued since 1971, focusing more specifically on the case of education, where major statistical efforts have been devoted to identifying patterns of disadvantage and integration. Finally, the article briefly examines current debates on the situation of ethnic minorities in the Netherlands in the context of growing questioning of established Dutch models of minority policy.13 p
Astrometric Positions and Proper Motions of 19 Radio Stars
We have used the Very Large Array, linked with the Pie Town Very Long
Baseline Array antenna, to determine astrometric positions of 19 radio stars in
the International Celestial Reference Frame (ICRF). The positions of these
stars were directly linked to the positions of distant quasars through phase
referencing observations. The positions of the ICRF quasars are known to 0.25
mas, thus providing an absolute reference at the angular resolution of our
radio observations. Average values for the errors in our derived positions for
all sources were 13 mas and 16 mas in R.A. and declination respectively, with
accuracies approaching 1-2 mas for some of the stars observed. Differences
between the ICRF positions of the 38 quasars, and those measured from our
observations showed no systematic offsets, with mean values of -0.3 mas in R.A.
and -1.0 mas in declination. Standard deviations of the quasar position
differences of 17 mas and 11 mas in R.A. and declination respectively, are
consistent with the mean position errors determined for the stars. Our measured
positions were combined with previous Very Large Array measurements taken from
1978-1995 to determine the proper motions of 15 of the stars in our list. With
mean errors of approximately 1.6 mas/yr, the accuracies of our proper motions
approach those derived from Hipparcos, and for a few of the stars in our
program, are better than the Hipparcos values. Comparing the positions of our
radio stars with the Hipparcos catalog, we find that at the epoch of our
observations, the two frames are aligned to within formal errors of
approximately 3 mas. This result confirms that the Hipparcos frame is inertial
at the expected level.Comment: 20 pages, 9 figures Accepted by the Astronomical Journal, 2003 March
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VLBI for Gravity Probe B. V. Proper Motion and Parallax of the Guide Star, IM Pegasi
We present the principal astrometric results of the very-long-baseline
interferometry (VLBI) program undertaken in support of the Gravity Probe B
(GP-B) relativity mission. VLBI observations of the GP-B guide star, the RS CVn
binary IM Pegasi (HR 8703), yielded positions at 35 epochs between 1997 and
2005. We discuss the statistical assumptions behind these results and our
methods for estimating the systematic errors. We find the proper motion of IM
Peg in an extragalactic reference frame closely related to the International
Celestial Reference Frame 2 (ICRF2) to be -20.83 +- 0.03 +- 0.09 mas/yr in
right ascension and -27.27 +- 0.03 +- 0.09 mas/yr in declination. For each
component the first uncertainty is the statistical standard error and the
second is the total standard error (SE) including plausible systematic errors.
We also obtain a parallax of 10.37 +- 0.07 mas (distance: 96.4 +- 0.7 pc), for
which there is no evidence of any significant contribution of systematic error.
Our parameter estimates for the ~25-day-period orbital motion of the stellar
radio emission have SEs corresponding to ~0.10 mas on the sky in each
coordinate. The total SE of our estimate of IM Peg's proper motion is ~30%
smaller than the accuracy goal set by the GP-B project before launch: 0.14
mas/yr for each coordinate of IM Peg's proper motion. Our results ensure that
the uncertainty in IM Peg's proper motion makes only a very small contribution
to the uncertainty of the GP-B relativity tests.Comment: Accepted for publication in the Astrophysical Journal Supplement
Serie
Competence of graph convolutional network in anti-money laundering in Bitcoin Blockchain
Graph networks are extensively used as an essential framework to analyse the interconnections between transactions and capture illicit behaviour in Bitcoin blockchain. Due to the complexity of Bitcoin transaction graph, the prediction of illicit transactions has become a challenging problem to unveil illicit services over the network. Graph Convolutional Network, a graph neural network based spectral approach, has recently emerged and gained much attention regarding graph-structured data. Previous research has highlighted the degraded performance of the latter approach to predict illicit transactions using, a Bitcoin transaction graph, so-called Elliptic data derived from Bitcoin blockchain. Motivated by the previous work, we seek to explore graph convolutions in a novel way. For this purpose, we present a novel approach that is modelled using the existing Graph Convolutional Network intertwined with linear layers. Concisely, we concatenate node embeddings obtained from graph convolutional layers with a single hidden layer derived from the linear transformation of the node feature matrix and followed by Multi-layer Perceptron. Our approach is evaluated using Elliptic data, wherein efficient accuracy is yielded. The proposed approach outperforms the original work of same data set
dictyBase, the model organism database for Dictyostelium discoideum
dictyBase () is the model organism database (MOD) for the social amoeba Dictyostelium discoideum. The unique biology and phylogenetic position of Dictyostelium offer a great opportunity to gain knowledge of processes not characterized in other organisms. The recent completion of the 34 MB genome sequence, together with the sizable scientific literature using Dictyostelium as a research organism, provided the necessary tools to create a well-annotated genome. dictyBase has leveraged software developed by the Saccharomyces Genome Database and the Generic Model Organism Database project. This has reduced the time required to develop a full-featured MOD and greatly facilitated our ability to focus on annotation and providing new functionality. We hope that manual curation of the Dictyostelium genome will facilitate the annotation of other genomes
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