141 research outputs found
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Beam Interaction Measurements with a Retarding Field Analyzer in a High-Current High-Vacuum Positively-Charged Particle Accelerator
A Retarding Field Analyzer (RFA) was inserted in a drift region of a magnetic transport section of the high-current experiment (HCX) that is at high-vacuum to measure ions and electrons resulting from beam interaction with background gas and walls. The ions are expelled during the beam by the space-charge potential and the electrons are expelled mainly at the end of the beam, when the beam potential decays. The ion energy distribution shows the beam potential of {approx} 2100 V and the beam-background gas total cross-section of 1.6x10{sup -20} m{sup 2}. The electron energy distribution reveals that the expelled electrons are mainly desorbed from the walls and gain {approx} 22 eV from the beam potential decaying with time before entering the RFA. Details of the RFA design and of the measured energy distributions are presented and discussed
Structural basis for potency differences between GDF8 and GDF11.
BACKGROUND: Growth/differentiation factor 8 (GDF8) and GDF11 are two highly similar members of the transforming growth factor β (TGFβ) family. While GDF8 has been recognized as a negative regulator of muscle growth and differentiation, there are conflicting studies on the function of GDF11 and whether GDF11 has beneficial effects on age-related dysfunction. To address whether GDF8 and GDF11 are functionally identical, we compared their signaling and structural properties. RESULTS: Here we show that, despite their high similarity, GDF11 is a more potent activator of SMAD2/3 and signals more effectively through the type I activin-like receptor kinase receptors ALK4/5/7 than GDF8. Resolution of the GDF11:FS288 complex, apo-GDF8, and apo-GDF11 crystal structures reveals unique properties of both ligands, specifically in the type I receptor binding site. Lastly, substitution of GDF11 residues into GDF8 confers enhanced activity to GDF8. CONCLUSIONS: These studies identify distinctive structural features of GDF11 that enhance its potency, relative to GDF8; however, the biological consequences of these differences remain to be determined
Simulations of lattice animals and trees
The scaling behaviour of randomly branched polymers in a good solvent is
studied in two to nine dimensions, using as microscopic models lattice animals
and lattice trees on simple hypercubic lattices. As a stochastic sampling
method we use a biased sequential sampling algorithm with re-sampling, similar
to the pruned-enriched Rosenbluth method (PERM) used extensively for linear
polymers. Essentially we start simulating percolation clusters (either site or
bond), re-weigh them according to the animal (tree) ensemble, and prune or
branch the further growth according to a heuristic fitness function. In
contrast to previous applications of PERM, this fitness function is {\it not}
the weight with which the actual configuration would contribute to the
partition sum, but is closely related to it. We obtain high statistics of
animals with up to several thousand sites in all dimension 2 <= d <= 9. In
addition to the partition sum (number of different animals) we estimate
gyration radii and numbers of perimeter sites. In all dimensions we verify the
Parisi-Sourlas prediction, and we verify all exactly known critical exponents
in dimensions 2, 3, 4, and >= 8. In addition, we present the hitherto most
precise estimates for growth constants in d >= 3. For clusters with one site
attached to an attractive surface, we verify the superuniversality of the
cross-over exponent at the adsorption transition predicted by Janssen and
Lyssy. Finally, we discuss the collapse of animals and trees, arguing that our
present version of the algorithm is also efficient for some of the models
studied in this context, but showing that it is {\it not} very efficient for
the `classical' model for collapsing animals.Comment: 17 pages RevTeX, 29 figures include
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Absolute Measurement of Electron Cloud Density
Beam interaction with background gas and walls produces ubiquitous clouds of stray electrons that frequently limit the performance of particle accelerator and storage rings. Counterintuitively we obtained the electron cloud accumulation by measuring the expelled ions that are originated from the beam-background gas interaction, rather than by measuring electrons that reach the walls. The kinetic ion energy measured with a retarding field analyzer (RFA) maps the depressed beam space-charge potential and provides the dynamic electron cloud density. Clearing electrode current measurements give the static electron cloud background that complements and corroborates with the RFA measurements, providing an absolute measurement of electron cloud density during a 5 {micro}s duration beam pulse in a drift region of the magnetic transport section of the High-Current Experiment (HCX) at LBNL
Radiative-capture cross sections for the La139(n,γ) reaction using thermal neutrons and structural properties of La140
A set of prompt partial γ-ray production cross sections from thermal neutron capture were measured for the 139La (n,γ) reaction using a guided beam of subthermal (thermal and cold) neutrons incident on a nat La2O3 target at the Prompt Gamma Activation Analysis facility of the Budapest Research Reactor. Absolute 140La cross sections were determined relative to the well-known comparator 35Cl(n,γ) cross sections from the irradiation of a stoichiometric nat LaCl3 sample. The total cross section for radiative thermal neutron capture on 139La from the sum of experimentally measured cross sections observed to directly feed the 140 La ground state was determined to be σ0 = 8.58(50) b. To assess completeness of the decay scheme and as a consistency check, the measured cross sections for transitions feeding the ground state from levels below a critical energy of Ec = 285 keV were combined with a modeled contribution accounting for ground-state feeding from the quasi continuum to arrive at a total cross section of σ0 = 9.36(74) b. In addition, a neutron-separation energy of Sn = 5161.001(21) keV was determined from a least-squares fit of the measured primary γ-ray energies to the low-lying levels of the 140La decay scheme. Furthermore, several nuclear structure improvements are proposed for the decay scheme. The measured cross-section and separation-energy results are comparable to earlier measurements of these quantities
National records of 3000 European bee and hoverfly species: A contribution to pollinator conservation
Pollinators play a crucial role in ecosystems globally, ensuring the seed production of most flowering plants. They are threatened by global changes and knowledge of their distribution at the national and continental levels is needed to implement efficient conservation actions, but this knowledge is still fragmented and/or difficult to access. As a step forward, we provide an updated list of around 3000 European bee and hoverfly species, reflecting their current distributional status at the national level (in the form of present, absent, regionally extinct, possibly extinct or non-native). This work was attainable by incorporating both published and unpublished data, as well as knowledge from a large set of taxonomists and ecologists in both groups. After providing the first National species lists for bees and hoverflies for many countries, we examine the current distributional patterns of these species and designate the countries with highest levels of species richness. We also show that many species are recorded in a single European country, highlighting the importance of articulating European and national conservation strategies. Finally, we discuss how the data provided here can be combined with future trait and Red List data to implement research that will further advance pollinator conservation
Updated S2 K guidelines for the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (EADV).
BACKGROUND
Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo-like lesions, and eczematous and/or urticarial erythematous lesions. The disease, which is significantly associated with neurological disorders, has high morbidity and severely impacts the quality of life.
OBJECTIVES AND METHODOLOGY
The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology sought to update the guidelines for the management of BP based on new clinical information, and new evidence on diagnostic tools and interventions. The recommendations are either evidence-based or rely on expert opinion. The degree of consent among all task force members was included.
RESULTS
Treatment depends on the severity of BP and patients' comorbidities. High-potency topical corticosteroids are recommended as the mainstay of treatment whenever possible. Oral prednisone at a dose of 0.5 mg/kg/day is a recommended alternative. In case of contraindications or resistance to corticosteroids, immunosuppressive therapies, such as methotrexate, azathioprine, mycophenolate mofetil or mycophenolate acid, may be recommended. The use of doxycycline and dapsone is controversial. They may be recommended, in particular, in patients with contraindications to oral corticosteroids. B-cell-depleting therapy and intravenous immunoglobulins may be considered in treatment-resistant cases. Omalizumab and dupilumab have recently shown promising results. The final version of the guideline was consented to by several patient organizations.
CONCLUSIONS
The guidelines for the management of BP were updated. They summarize evidence- and expert-based recommendations useful in clinical practice
Novel missense mutations in the glycine receptor β subunit gene (GLRB) in startle disease
Startle disease is a rare, potentially fatal neuromotor disorder characterized by exaggerated startle reflexes and hypertonia in response to sudden unexpected auditory, visual or tactile stimuli. Mutations in the GlyR alpha(1) subunit gene (GLRA1) are the major cause of this disorder, since remarkably few individuals with mutations in the GlyR beta subunit gene (GLRB) have been found to date. Systematic DNA sequencing of GLRB in individuals with hyperekplexia revealed new missense mutations in GLRB, resulting in M177R, L285R and W310C substitutions. The recessive mutation M177R results in the insertion of a positively-charged residue into a hydrophobic pocket in the extracellular domain, resulting in an increased EC50 and decreased maximal responses of alpha(1)beta GlyRs. The de novo mutation L285R results in the insertion of a positively-charged side chain into the pore-lining 9' position. Mutations at this site are known to destabilize the channel closed state and produce spontaneously active channels. Consistent with this, we identified a leak conductance associated with spontaneous GlyR activity in cells expressing alpha(1)beta(L285R) GlyRs. Peak currents were also reduced for alpha(1)beta(L285R) GlyRs although glycine sensitivity was normal. W310C was predicted to interfere with hydrophobic side-chain stacking between M1, M2 and M3. We found that W310C had no effect on glycine sensitivity, but reduced maximal currents in alpha(1)beta GlyRs in both homozygous (alpha(1)beta(W310C)) and heterozygous (alpha(1)beta beta(W310C)) stoichiometries. Since mild startle symptoms were reported in W310C carriers, this may represent an example of incomplete dominance in startle disease, providing a potential genetic explanation for the 'minor' form of hyperekplexia. (C) 2012 Elsevier Inc. All rights reserved
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