868 research outputs found
Improved diamond coring bits developed for dry and chip-flush drilling
Two rotary diamond bit designs, one operating with a chip-flushing fluid, the second including auger section to remove drilled chips, enhance usefulness of tool for exploratory and industrial core-drilling of hard, abrasive mineral deposits and structural masonry
Structural and chemical embrittlement of grain boundaries by impurities: a general theory and first principles calculations for copper
First principles calculations of the Sigma 5 (310)[001] symmetric tilt grain
boundary in Cu with Bi, Na, and Ag substitutional impurities provide evidence
that in the phenomenon of Bi embrittlement of Cu grain boundaries electronic
effects do not play a major role; on the contrary, the embrittlement is mostly
a structural or "size" effect. Na is predicted to be nearly as good an
embrittler as Bi, whereas Ag does not embrittle the boundary in agreement with
experiment. While we reject the prevailing view that "electronic" effects
(i.e., charge transfer) are responsible for embrittlement, we do not exclude
the role of chemistry. However numerical results show a striking equivalence
between the alkali metal Na and the semi metal Bi, small differences being
accounted for by their contrasting "size" and "softness" (defined here). In
order to separate structural and chemical effects unambiguously if not
uniquely, we model the embrittlement process by taking the system of grain
boundary and free surfaces through a sequence of precisely defined gedanken
processes; each of these representing a putative mechanism. We thereby identify
three mechanisms of embrittlement by substitutional impurities, two of which
survive in the case of embrittlement or cohesion enhancement by interstitials.
Two of the three are purely structural and the third contains both structural
and chemical elements that by their very nature cannot be further unravelled.
We are able to take the systems we study through each of these stages by
explicit computer simulations and assess the contribution of each to the nett
reduction in intergranular cohesion. The conclusion we reach is that
embrittlement by both Bi and Na is almost exclusively structural in origin;
that is, the embrittlement is a size effect.Comment: 13 pages, 5 figures; Accepted in Phys. Rev.
2018 Ottawa consensus statement : Selection and recruitment to the healthcare professions
Acknowledgments: The authors thank Tom Kinirons and Sarah Stott of Work Psychology Group for supporting the consensus group discussions and workshops, and in preparing the final manuscript. We also gratefully acknowledge Professor Lambert Schuwirth for his helpful comments on an earlier draft of this paperPeer reviewedPostprin
Conformation-dependent GAD65 autoantibodies in diabetes
Aims/hypothesis. Conformation-dependent autoantibodies directed against GAD65 are markers of Type 1 diabetes. In this study we aimed to determine whether the substitution of GAD65 with GAD67 amino acids would affect the binding of conformation-dependent GAD65 autoantibodies. Methods. We used PCR-based site-directed mutagenesis to generate a series of mutated GAD65 cDNA constructs in which specific GAD65 coding sequences for regions of the protein critical for autoantibody binding were replaced with GAD67 coding sequences. Results. The introduction of a point mutation at position 517, substituting glutamic acid with proline, markedly reduced the binding of disease-associated GAD65 antibodies. The binding of GAD65 antibodies to the E517P mutant was reduced in the sera of all newly diagnosed Type 1 diabetes patients (n=85) by a mean of 72% (p<0.0001) compared with binding to wild-type GAD65. Patients with latent autoimmune diabetes in adults (n=24) showed a similar reduction in binding (79% reduction, p<0.0001). First-degree relatives who subsequently progressed to Type 1 diabetes (n=12) showed a reduction in binding of 80% compared with a reduction of only 65% among relatives who had not progressed to disease (n=38; p=0.025). In healthy GAD65Ab-positive individuals who did not progress to diabetes during a 9-year follow-up period (n=51), binding to GAD65-E517P was reduced by only 28% compared with binding to wild-type GAD65. Conclusions/interpretation. Differences in autoantibody binding to wild-type GAD65 versus GAD65-E517P may provide predictive information about Type 1 diabetes risk beyond that provided by the presence or absence of GAD65 autoantibodies. Lack of binding to mutant GAD65-E517P defines GAD65-positive individuals who are at higher risk of developing diabetes
Mutual Zonated Interactions of Wnt and Hh Signaling Are Orchestrating the Metabolism of the Adult Liver in Mice and Human
The Hedgehog (Hh) and Wnt/β-Catenin (Wnt) cascades are morphogen pathways whose pronounced influence on adult liver metabolism has been identified in recent years. How both pathways communicate and control liver metabolic functions are largely unknown. Detecting core components of Wnt and Hh signaling and mathematical modeling showed that both pathways in healthy liver act largely complementary to each other in the pericentral (Wnt) and the periportal zone (Hh) and communicate mainly by mutual repression. The Wnt/Hh module inversely controls the spatiotemporal operation of various liver metabolic pathways, as revealed by transcriptome, proteome, and metabolome analyses. Shifting the balance to Wnt (activation) or Hh (inhibition) causes pericentralization and periportalization of liver functions, respectively. Thus, homeostasis of the Wnt/Hh module is essential for maintaining proper liver metabolism and to avoid the development of certain metabolic diseases. With caution due to minor species-specific differences, these conclusions may hold for human liver as well
ABC Effect in Basic Double-Pionic Fusion --- Observation of a new resonance?
We report on a high-statistics measurement of the basic double pionic fusion
reaction over the energy region of the so-called ABC
effect, a pronounced low-mass enhancement in the -invariant mass
spectrum. The measurements were performed with the WASA detector setup at COSY.
The data reveal the ABC effect to be associated with a Lorentzian shaped energy
dependence in the integral cross section. The observables are consistent with a
resonance with in both and systems.
Necessary further tests of the resonance interpretation are discussed
Long-Lived Plasma Cells and Memory B Cells Produce Pathogenic Anti-GAD65 Autoantibodies in Stiff Person Syndrome
Stiff person syndrome (SPS) is a rare, neurological disorder characterized by sudden cramps and spasms. High titers of enzyme-inhibiting IgG autoantibodies against the 65 kD isoform of glutamic acid decarboxylase (GAD65) are a hallmark of SPS, implicating an autoimmune component in the pathology of the syndrome. Studying the B cell compartment and the anti-GAD65 B cell response in two monozygotic twins suffering from SPS, who were treated with the B cell-depleting monoclonal anti-CD20 antibody rituximab, we found that the humoral autoimmune response in SPS is composed of a rituximab-sensitive part that is rapidly cleared after treatment, and a rituximab-resistant component, which persists and acts as a reservoir for autoantibodies inhibiting GAD65 enzyme activity. Our data show that these potentially pathogenic anti-GAD65 autoantibodies are secreted by long-lived plasma cells, which may either be persistent or develop from rituximab-resistant memory B lymphocytes. Both subsets represent only a fraction of anti-GAD65 autoantibody secreting cells. Therefore, the identification and targeting of this compartment is a key factor for successful treatment planning of SPS and of similar autoimmune diseases
Climate change and outdoor regional living plant collections: an example from mainland Portugal
Original PaperClimate change threatens not only plant species occurring naturally, but also
impacts on regional living plant collections, which play an important role in ex situ
conservation strategies. In the last few years, several global circulation models have been
used to predict different global climate change scenarios. Due to their coarse resolutions,
and while more detailed regional approaches are not available, downscaling techniques
have been proposed, as a very simple first approach to increase detail. We analysed seven
sites on mainland Portugal with potential for species conservation (four botanic gardens
and three universities), in the light of downscaled climate change scenarios, using an
environmental envelope approach and a predefined bioclimatic neighbourhood for each
site. Thresholds for the bioclimatic neighbourhood were based on Rivas-Martı´nez’s Bioclimatic
Classification of the Earth. For each site, the expected geographical shift of its
original bioclimatic neighbourhood (1950–2000) was mapped for 2020, 2050 and 2080.
Analysing those shifts enabled us to delineate knowledge-transfer paths between sites,
according to the analysed scenarios. We concluded that, according to the Intergovernmental
Panel on Climate Change A2 scenario, all considered sites will be outside the
predefined bioclimatic neighbourhood by 2080, while according to the B2 scenario all of
them will be inside that neighbourhood, although sometimes marginally so. Therefore, the
implementation of global sustainability measures as considered in the B2 scenario family
can be of great importance in order to delay significantly the impacts of climate change,
giving extra time for the adaptation of the outdoor regional living plant collectionsinfo:eu-repo/semantics/publishedVersio
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