362 research outputs found
Measurement of the Proton and Deuteron Spin Structure Function g_1 in the Resonance Region
We have measured the proton and deuteron spin structure functions g_1^p and
g_1^d in the region of the nucleon resonances for W^2 < 5 GeV^2 and and GeV^2 by inelastically scattering 9.7 GeV polarized
electrons off polarized and targets. We observe
significant structure in g_1^p in the resonance region. We have used the
present results, together with the deep-inelastic data at higher W^2, to
extract . This is the first
information on the low-Q^2 evolution of Gamma toward the Gerasimov-Drell-Hearn
limit at Q^2 = 0.Comment: 7 pages, 2 figure
Timed inhibition of CDC7 increases CRISPR-Cas9 mediated templated repair.
Repair of double strand DNA breaks (DSBs) can result in gene disruption or gene modification via homology directed repair (HDR) from donor DNA. Altering cellular responses to DSBs may rebalance editing outcomes towards HDR and away from other repair outcomes. Here, we utilize a pooled CRISPR screen to define host cell involvement in HDR between a Cas9 DSB and a plasmid double stranded donor DNA (dsDonor). We find that the Fanconi Anemia (FA) pathway is required for dsDonor HDR and that other genes act to repress HDR. Small molecule inhibition of one of these repressors, CDC7, by XL413 and other inhibitors increases the efficiency of HDR by up to 3.5 fold in many contexts, including primary T cells. XL413 stimulates HDR during a reversible slowing of S-phase that is unexplored for Cas9-induced HDR. We anticipate that XL413 and other such rationally developed inhibitors will be useful tools for gene modification
Set optimization - a rather short introduction
Recent developments in set optimization are surveyed and extended including
various set relations as well as fundamental constructions of a convex analysis
for set- and vector-valued functions, and duality for set optimization
problems. Extensive sections with bibliographical comments summarize the state
of the art. Applications to vector optimization and financial risk measures are
discussed along with algorithmic approaches to set optimization problems
Precision measurement of the deuteron spin structure function
We report on a high-statistics measurement of the deuteron spin structure function g[sup d][sub 1] at a beam energy of 29 GeV in the kinematic range 0.029 < x < 0.8 and 1 < Q2 < 10 (GeV/c)2. The integral Gamma [sup d][sub 1] = (integral)[sup 1][sub 0]g[sup d][sub 1]dx evaluated at fixed Q2 = 3 (GeV/c)2 gives 0.042 ± 0.003(stat) ± 0.004(syst). Combining this result with our earlier measurement of g[sup p][sub 1], we find Gamma [sup p][sub 1]- Gamma [sup n][sub 1] = 0.163 ± 0.010(stat) ± 0.016(syst), which agrees with the prediction of the Bjorken sum rule with O( alpha [sup 3][sub s]) corrections, Gamma [sup p][sub 1]- Gamma [sup n][sub 1] = 0.171 ± 0.008. We find the quark contribution to the proton helicity to be Delta q = 0.30 ± 0.06
Machine layout and performance
The Large Hadron Collider (LHC) is one of the largest scientific instruments ever built. Since opening up a new
energy frontier for exploration in 2010, it has gathered a global user community of about 7,000 scientists working
in fundamental particle physics and the physics of hadronic matter at extreme temperature and density. To sustain
and extend its discovery potential, the LHC will need a major upgrade in the 2020s. This will increase its luminosity
(rate of collisions) by a factor of five beyond the original design value and the integrated luminosity (total
collisions created) by a factor ten. The LHC is already a highly complex and exquisitely optimised machine so this
upgrade must be carefully conceived and will require about ten years to implement. The new configuration, known
as High Luminosity LHC (HL-LHC), will rely on a number of key innovations that push accelerator technology
beyond its present limits. Among these are cutting-edge 11-12 tesla superconducting magnets, compact superconducting
cavities for beam rotation with ultra-precise phase control, new technology and physical processes
for beam collimation and 300 metre-long high-power superconducting links with negligible energy dissipation.
The present document describes the technologies and components that will be used to realise the project and is
intended to serve as the basis for the detailed engineering design of HL-LHC
Upregulation of α7 Nicotinic Receptors by Acetylcholinesterase C-Terminal Peptides
BACKGROUND: The alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR) is well known as a potent calcium ionophore that, in the brain, has been implicated in excitotoxicity and hence in the underlying mechanisms of neurodegenerative disorders such as Alzheimer's disease. Previous research implied that the activity of this receptor may be modified by exposure to a peptide fragment derived from the C-terminal region of the enzyme acetylcholinesterase. This investigation was undertaken to determine if the functional changes observed could be attributed to peptide binding interaction with the alpha7-nAChR, or peptide modulation of receptor expression. METHODOLOGY/PRINCIPAL FINDINGS: This study provides evidence that two peptides derived from the C-terminus of acetylcholinesterase, not only selectively displace specific bungarotoxin binding at the alpha7-nAChR, but also alter receptor binding properties for its familiar ligands, including the alternative endogenous agonist choline. Of more long-term significance, these peptides also induce upregulation of alpha7-nAChR mRNA and protein expression, as well as enhancing receptor trafficking to the plasma membrane. CONCLUSIONS/SIGNIFICANCE: The results reported here demonstrate a hitherto unknown relationship between the alpha7-nAChR and the non-enzymatic functions of acetylcholinesterase, mediated independently by its C-terminal domain. Such an interaction may prove valuable as a pharmacological tool, prompting new approaches for understanding, and combating, the process of neurodegeneration
Upregulation of α7 Nicotinic Receptors by Acetylcholinesterase C-Terminal Peptides
BACKGROUND: The alpha-7 nicotinic acetylcholine receptor (alpha7-nAChR) is well known as a potent calcium ionophore that, in the brain, has been implicated in excitotoxicity and hence in the underlying mechanisms of neurodegenerative disorders such as Alzheimer's disease. Previous research implied that the activity of this receptor may be modified by exposure to a peptide fragment derived from the C-terminal region of the enzyme acetylcholinesterase. This investigation was undertaken to determine if the functional changes observed could be attributed to peptide binding interaction with the alpha7-nAChR, or peptide modulation of receptor expression. METHODOLOGY/PRINCIPAL FINDINGS: This study provides evidence that two peptides derived from the C-terminus of acetylcholinesterase, not only selectively displace specific bungarotoxin binding at the alpha7-nAChR, but also alter receptor binding properties for its familiar ligands, including the alternative endogenous agonist choline. Of more long-term significance, these peptides also induce upregulation of alpha7-nAChR mRNA and protein expression, as well as enhancing receptor trafficking to the plasma membrane. CONCLUSIONS/SIGNIFICANCE: The results reported here demonstrate a hitherto unknown relationship between the alpha7-nAChR and the non-enzymatic functions of acetylcholinesterase, mediated independently by its C-terminal domain. Such an interaction may prove valuable as a pharmacological tool, prompting new approaches for understanding, and combating, the process of neurodegeneration
Measurements of R=sigma_L/sigma_T for 0.03<x<0.1 and Fit to World Data
Measurements were made at SLAC of the cross section for scattering 29 GeV
electrons from carbon at a laboratory angle of 4.5 degrees, corresponding to
0.03<x<0.1 and 1.3<Q^2<2.7 GeV^2. Values of R=sigma_L/sigma_T were extracted in
this kinematic range by comparing these data to cross sections measured at a
higher beam energy by the NMC collaboration. The results are in reasonable
agreement with pQCD calculations and with extrapolations of the R1990
parameterization of previous data. A new fit is made including these data and
other recent results.Comment: 8 pages, 4 figures, late
LICSTER -- A Low-cost ICS Security Testbed for Education and Research
Unnoticed by most people, Industrial Control Systems (ICSs) control entire
productions and critical infrastructures such as water distribution, smart grid
and automotive manufacturing. Due to the ongoing digitalization, these systems
are becoming more and more connected in order to enable remote control and
monitoring. However, this shift bears significant risks, namely a larger attack
surface, which can be exploited by attackers. In order to make these systems
more secure, it takes research, which is, however, difficult to conduct on
productive systems, since these often have to operate twenty-four-seven.
Testbeds are mostly very expensive or based on simulation with no real-world
physical process. In this paper, we introduce LICSTER, an open-source low-cost
ICS testbed, which enables researchers and students to get hands-on experience
with industrial security for about 500 Euro. We provide all necessary material
to quickly start ICS hacking, with the focus on low-cost and open-source for
education and research
The Role of Host Genetics in Susceptibility to Influenza: A Systematic Review
Background: The World Health Organization has identified studies of the role of host genetics on susceptibility to severe influenza as a priority. A systematic review was conducted to summarize the current state of evidence on the role of host genetics in susceptibility to influenza (PROSPERO registration number: CRD42011001380). Methods and Findings: PubMed, Web of Science, the Cochrane Library, and OpenSIGLE were searched using a pre-defined strategy for all entries up to the date of the search. Two reviewers independently screened the title and abstract of 1,371 unique articles, and 72 full text publications were selected for inclusion. Mouse models clearly demonstrate that host genetics plays a critical role in susceptibility to a range of human and avian influenza viruses. The Mx genes encoding interferon inducible proteins are the best studied but their relevance to susceptibility in humans is unknown. Although the MxA gene should be considered a candidate gene for further study in humans, over 100 other candidate genes have been proposed. There are however no data associating any of these candidate genes to susceptibility in humans, with the only published study in humans being under-powered. One genealogy study presents moderate evidence of a heritable component to the risk of influenza-associated death, and while the marked familial aggregation of H5N1 cases is suggestive of host genetic factors, this remains unproven. Conclusion: The fundamental question ‘‘Is susceptibility to severe influenza in humans heritable?’ ’ remains unanswered. No
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