571 research outputs found
Correction: Meta-Analysis of the Relationship between Multiple Sclerosis and Migraine.
This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.PMCID: PMC3613438PMCID: PMC3613438PMCID: PMC3613438PMCID: PMC3613438[This corrects the article on p. e45295 in vol. 7.]
Age Problem in the Holographic Dark Energy Model
In this note, we test the original holographic dark energy model with some
old high redshift objects. The main idea is very simple: the universe cannot be
younger than its constituents. We find that the original holographic dark
energy model can be ruled out, unless a lower Hubble constant is taken.Comment: 12 pages, 3 tables, 3 figures, revtex4; v2: accepted for publication
in Phys. Rev. D; v3: published versio
Focused Ion Microbeam Irradiation Induces Clustering of DNA Double-Strand Breaks in Heterochromatin Visualized by Nanoscale-Resolution Electron Microscopy
Background: Charged-particle radiotherapy is an emerging treatment modality for radioresistant tumors. The enhanced effectiveness of high-energy particles (such as heavy ions) has been
related to the spatial clustering of DNA lesions due to highly localized energy deposition. Here, DNA
damage patterns induced by single and multiple carbon ions were analyzed in the nuclear chromatin
environment by different high-resolution microscopy approaches. Material and Methods: Using the
heavy-ion microbeam SNAKE, fibroblast monolayers were irradiated with defined numbers of carbon
ions (1/10/100 ions per pulse, ipp) focused to micrometer-sized stripes or spots. Radiation-induced
lesions were visualized as DNA damage foci (ÎłH2AX, 53BP1) by conventional fluorescence and stimulated emission depletion (STED) microscopy. At micro- and nanoscale level, DNA double-strand
breaks (DSBs) were visualized within their chromatin context by labeling the Ku heterodimer. Single
and clustered pKu70-labeled DSBs were quantified in euchromatic and heterochromatic regions at
0.1 h, 5 h and 24 h post-IR by transmission electron microscopy (TEM). Results: Increasing numbers
of carbon ions per beam spot enhanced spatial clustering of DNA lesions and increased damage
complexity with two or more DSBs in close proximity. This effect was detectable in euchromatin, but
was much more pronounced in heterochromatin. Analyzing the dynamics of damage processing, our
findings indicate that euchromatic DSBs were processed efficiently and repaired in a timely manner.
In heterochromatin, by contrast, the number of clustered DSBs continuously increased further over
the first hours following IR exposure, indicating the challenging task for the cell to process highly
clustered DSBs appropriately. Conclusion: Increasing numbers of carbon ions applied to sub-nuclear
chromatin regions enhanced the spatial clustering of DSBs and increased damage complexity, this
being more pronounced in heterochromatic regions. Inefficient processing of clustered DSBs may
explain the enhanced therapeutic efficacy of particle-based radiotherapy in cancer treatment
Nogo receptor is involved in the adhesion of dendritic cells to myelin
BACKGROUND: Nogo-66 receptor NgR1 and its structural homologue NgR2 are binding proteins for a number of myelin-associated inhibitory factors. After neuronal injury, these inhibitory factors are responsible for preventing axonal outgrowth via their interactions with NgR1 and NgR2 expressed on neurons. In vitro, cells expressing NgR1/2 are inhibited from adhering to and spreading on a myelin substrate. Neuronal injury also results in the presence of dendritic cells (DCs) in the central nervous system, where they can come into contact with myelin debris. The exact mechanisms of interaction of immune cells with CNS myelin are, however, poorly understood.
METHODS: Human DCs were differentiated from peripheral blood monocytes and mouse DCs were differentiated from wild type and NgR1/NgR2 double knockout bone marrow precursors. NgR1 and NgR2 expression were determined with quantitative real time PCR and immunoblot, and adhesion of cells to myelin was quantified.
RESULTS: We demonstrate that human immature myeloid DCs express NgR1 and NgR2, which are then down-regulated upon maturation. Human mature DCs also adhere to a much higher extent to a myelin substrate than immature DCs. We observe the same effect when the cells are plated on Nogo-66-His (binding peptide for NgR1), but not on control proteins. Mature DCs taken from Ngr1/2 knockout mice adhere to a much higher extent to myelin compared to wild type mouse DCs. In addition, Ngr1/2 knockout had no effect on in vitro DC differentiation or phenotype.
CONCLUSIONS: These results indicate that a lack of NgR1/2 expression promotes the adhesion of DCs to myelin. This interaction could be important in neuroinflammatory disorders such as multiple sclerosis in which peripheral immune cells come into contact with myelin debris
A Single Dose of Neuron-Binding Human Monoclonal Antibody Improves Spontaneous Activity in a Murine Model of Demyelination
Our laboratory demonstrated that a natural human serum antibody, sHIgM12, binds to neurons in vitro and promotes neurite outgrowth. We generated a recombinant form, rHIgM12, with identical properties. Intracerebral infection with Theiler's Murine Encephalomyelitis Virus (TMEV) of susceptible mouse strains results in chronic demyelinating disease with progressive axonal loss and neurologic dysfunction similar to progressive forms of multiple sclerosis. To study the effects of rHIgM12 on the motor function of TMEV-infected mice, we monitored spontaneous nocturnal activity over many weeks. Nocturnal behavior is a sensitive measure of rodent neurologic function because maximal activity changes are expected to occur during the normally active night time monitoring period. Mice were placed in activity boxes eight days prior to treatment to collect baseline spontaneous activity. After treatment, activity in each group was continuously recorded over 8 weeks. We chose a long 8-week monitoring period for two reasons: (1) we previously demonstrated that IgM induced remyelination is present by 5 weeks post treatment, and (2) TMEV-induced demyelinating disease in this strain progresses very slowly. Due to the long observation periods and large data sets, differences among treatment groups may be difficult to appreciate studying the original unfiltered recordings. To clearly delineate changes in the highly fluctuating original data we applied three different methods: (1) binning, (2) application of Gaussian low-pass filters (GF) and (3) polynomial fitting. Using each of the three methods we showed that compared to control IgM and saline, early treatment with rHIgM12 induced improvement in both horizontal and vertical motor function, whereas later treatment improved only horizontal activity. rHIgM12 did not alter activity of normal, uninfected mice. This study supports the hypothesis that treatment with a neuron-binding IgM not only protects neurons in vitro, but also influences functional motor improvement
The unusual planetary nebula nucleus in the Galactic open cluster M37 and six further hot white dwarf candidates
Planetary nebulae in Galactic open star clusters are rare objects; only three
are known to date. They are of particular interest because their distance can
be determined with high accuracy, allowing one to characterize the physical
properties of the planetary nebula and its ionizing central star with high
confidence. Here we present the first quantitative spectroscopic analysis of a
central star in an open cluster, namely the faint nucleus of IPHASX
J055226.2323724 in M37. This cluster contains 14 confirmed white dwarf
members, which were previously used to study the initial-to-final-mass relation
of white dwarfs, and six additional white dwarf candidates. We performed an
atmosphere modeling of spectra taken with the 10m Gran Telescopio Canarias. The
central star is a hot hydrogen-deficient white dwarf with an effective
temperature of 90,000 K and spectral type PG1159 (helium- and carbon-rich). We
know it is about to transform into a helium-rich DO white dwarf because the
relatively low atmospheric carbon abundance indicates ongoing gravitational
settling of heavy elements. The star belongs to a group of hot white dwarfs
that exhibit ultrahigh-excitation spectral lines possibly emerging from
shock-heated material in a magnetosphere. We find a relatively high stellar
mass of M. This young white dwarf is
important for the semi-empirical initial-final mass relation because any
uncertainty related to white-dwarf cooling theory is insignificant with respect
to the pre-white-dwarf timescale. Its post-asymptotic-giant-branch age of
yr suggests that the extended planetary nebula is
extraordinarily old. We also performed a spectroscopic analysis of the six
other white dwarf candidates of M37, confirming one as a cluster member.Comment: Accepted for publication in A&
Meta-Analysis of the Relationship between Multiple Sclerosis and Migraine
BACKGROUND: Studies investigating a proposed association between multiple sclerosis (MS) and migraine have produced conflicting results and a great range in the prevalence rate of migraine in MS patients. By meta-analysing all available data we aimed to establish an overall estimate of any association in order to more accurately inform clinicians and care-givers about a potential association between MS and migraine. METHODS: Pubmed and EMBASE were searched to identify suitable studies. Studies were included if they were a case-control study or cohort study in which controls were not reported to have another neurological condition, were available in English, and specified migraine as a headache sub-type. The odds ratio (OR) of migraine in MS patients vs. controls was calculated using the inverse variance with random effects model in Review Manager 5.1. RESULTS: Eight studies were selected for inclusion, yielding a total of 1864 MS patients and 261563 control subjects. We found a significant association between migraine and MS (ORâ=â2.60, 95% CI 1.12-6.04), although there was significant heterogeneity. Sensitivity analysis showed that migraine without aura was associated with MS ORâ=â2.29 (95% CI 1.14-4.58), with no significant heterogeneity. CONCLUSIONS: MS patients are more than twice as likely to report migraine as controls. Care providers should be alerted to ask MS patients about migraine in order to treat it and potentially improve quality of life. Future work should further investigate the temporal relationship of this association and relationship to the clinical characteristics of MS
Materials Screening for Disorder-Controlled Chalcogenide Crystals for Phase-Change Memory Applications
Tailoring the degree of disorder in chalcogenide phase-change materials (PCMs) plays an essential role in nonvolatile memory devices and neuro-inspired computing. Upon rapid crystallization from the amorphous phase, the flagship GeâSbâTe PCMs form metastable rocksalt-like structures with an unconventionally high concentration of vacancies, which results in disordered crystals exhibiting Anderson-insulating transport behavior. Here, ab initio simulations and transport experiments are combined to extend these concepts to the parent compound of GeâSbâTe alloys, viz., binary Sb2Te3, in the metastable rocksalt-type modification. Then a systematic computational screening over a wide range of homologous, binary and ternary chalcogenides, elucidating the critical factors that affect the stability of the rocksalt structure is carried out. The findings vastly expand the family of disorder-controlled main-group chalcogenides toward many more compositions with a tunable bandgap size for demanding phase-change applications, as well as a varying strength of spinâorbit interaction for the exploration of potential topological Anderson insulators
Exploring CEvNS with NUCLEUS at the Chooz Nuclear Power Plant
Coherent elastic neutrino-nucleus scattering (CENS) offers a unique way
to study neutrino properties and to search for new physics beyond the Standard
Model. Nuclear reactors are promising sources to explore this process at low
energies since they deliver large fluxes of (anti-)neutrinos with typical
energies of a few MeV. In this paper, a new-generation experiment to study
CENS is described. The NUCLEUS experiment will use cryogenic detectors
which feature an unprecedentedly low energy threshold and a time response fast
enough to be operated in above-ground conditions. Both sensitivity to
low-energy nuclear recoils and a high event rate tolerance are stringent
requirements to measure CENS of reactor antineutrinos. A new experimental
site, denoted the Very-Near-Site (VNS) at the Chooz nuclear power plant in
France is described. The VNS is located between the two 4.25 GW
reactor cores and matches the requirements of NUCLEUS. First results of on-site
measurements of neutron and muon backgrounds, the expected dominant background
contributions, are given. In this paper a preliminary experimental setup with
dedicated active and passive background reduction techniques is presented.
Furthermore, the feasibility to operate the NUCLEUS detectors in coincidence
with an active muon-veto at shallow overburden is studied. The paper concludes
with a sensitivity study pointing out the promising physics potential of
NUCLEUS at the Chooz nuclear power plant
WD + MS systems as the progenitor of SNe Ia
We show the initial and final parameter space for SNe Ia in a () plane and find that the positions of some famous
recurrent novae, as well as a supersoft X-ray source (SSS), RX J0513.9-6951,
are well explained by our model. The model can also explain the space velocity
and mass of Tycho G, which is now suggested to be the companion star of Tycho's
supernova. Our study indicates that the SSS, V Sge, might be the potential
progenitor of supernovae like SN 2002ic if the delayed dynamical-instability
model due to Han & Podsiadlowski (2006) is appropriate. Following the work of
Meng, Chen & Han (2009), we found that the SD model (WD + MS) with an optically
thick wind can explain the birth rate of supernovae like SN 2006X and reproduce
the distribution of the color excess of SNe Ia. The model also predicts that at
least 75% of all SNe Ia may show a polarization signal in their spectra.Comment: 6 pages, 2 figures, accepted for publication in Astrophysics & Space
Science (Proceeding of the 4th Meeting on Hot Subdwarf Stars and Related
Objects, edited by Zhanwen Han, Simon Jeffery & Philipp Podsiadlowski
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