399 research outputs found
Quantitative localized proton-promoted dissolution kinetics of calcite using scanning electrochemical microscopy (SECM)
Scanning electrochemical microscopy (SECM) has been used to determine quantitatively the kinetics of proton-promoted dissolution of the calcite (101̅4) cleavage surface (from natural “Iceland Spar”) at the microscopic scale. By working under conditions where the probe size is much less than the characteristic dislocation spacing (as revealed from etching), it has been possible to measure kinetics mainly in regions of the surface which are free from dislocations, for the first time. To clearly reveal the locations of measurements, studies focused on cleaved “mirror” surfaces, where one of the two faces produced by cleavage was etched freely to reveal defects intersecting the surface, while the other (mirror) face was etched locally (and quantitatively) using SECM to generate high proton fluxes with a 25 μm diameter Pt disk ultramicroelectrode (UME) positioned at a defined (known) distance from a crystal surface. The etch pits formed at various etch times were measured using white light interferometry to ascertain pit dimensions. To determine quantitative dissolution kinetics, a moving boundary finite element model was formulated in which experimental time-dependent pit expansion data formed the input for simulations, from which solution and interfacial concentrations of key chemical species, and interfacial fluxes, could then be determined and visualized. This novel analysis allowed the rate constant for proton attack on calcite, and the order of the reaction with respect to the interfacial proton concentration, to be determined unambiguously. The process was found to be first order in terms of interfacial proton concentration with a rate constant k = 6.3 (± 1.3) × 10–4 m s–1. Significantly, this value is similar to previous macroscopic rate measurements of calcite dissolution which averaged over large areas and many dislocation sites, and where such sites provided a continuous source of steps for dissolution. Since the local measurements reported herein are mainly made in regions without dislocations, this study demonstrates that dislocations and steps that arise from such sites are not needed for fast proton-promoted calcite dissolution. Other sites, such as point defects, which are naturally abundant in calcite, are likely to be key reaction sites
Single Spin Superconductivity: Formulation and Ginzburg-Landau Theory
We describe a novel superconducting phase that arises due to a pairing
instability of the half-metallic antiferromagnetic (HM AFM) normal state. This
single spin superconducting (SSS) phase contains broken time reversal symmetry
in addition to broken gauge symmetry, the former due to the underlying magnetic
order in the normal state. A classification of normal state symmetries leads to
the conclusion that the HM AFM normal phase whose point group contains the
inversion operator contains the least symmetry possible which still allows for
a zero momentum pairing instability. The Ginzburg-Landau free energy for the
superconducting order parameter is constructed consistent with the symmetry of
the normal phase, electromagnetic gauge invariance and the crystallographic
point group symmetry including inversion. For cubic, hexagonal and tetragonal
point groups, the possible symmetries of the superconducting phase are
classified, and the free energy is used to construct a generalized phase
diagram. We identify the leading candidate out of the possible SSS phases for
each point group. The symmetry of the superconducting phase is used to
determine the cases where the gap function has generic zeros (point or line
nodes) on the Fermi surface. Such nodes always occur, hence thermodynamic
properties will have power-law behavior at low temperature.Comment: 39 pages, RevTeX, 4 PostScript figures included, submitted to Phys.
Rev.
Evidence for significant projectile–target nucleus scattering in single ionization of helium
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A conserved fungal glycosyltransferase facilitates pathogenesis of plants by enabling hyphal growth on solid surfaces
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Pathogenic fungi must extend filamentous hyphae across solid surfaces to cause diseases of plants. However, the full inventory of genes which support this is incomplete and many may be currently concealed due to their essentiality for the hyphal growth form. During a random T-DNA mutagenesis screen performed on the pleomorphic wheat (Triticum aestivum) pathogen Zymoseptoria tritici, we acquired a mutant unable to extend hyphae specifically when on solid surfaces. In contrast “yeast-like” growth, and all other growth forms, were unaffected. The inability to extend surface hyphae resulted in a complete loss of virulence on plants. The affected gene encoded a predicted type 2 glycosyltransferase (ZtGT2). Analysis of >800 genomes from taxonomically diverse fungi highlighted a generally widespread, but discontinuous, distribution of ZtGT2 orthologues, and a complete absence of any similar proteins in non-filamentous ascomycete yeasts. Deletion mutants of the ZtGT2 orthologue in the taxonomically un-related fungus Fusarium graminearum were also severely impaired in hyphal growth and non-pathogenic on wheat ears. ZtGT2 expression increased during filamentous growth and electron microscopy on deletion mutants (ΔZtGT2) suggested the protein functions to maintain the outermost surface of the fungal cell wall. Despite this, adhesion to leaf surfaces was unaffected in ΔZtGT2 mutants and global RNAseq-based gene expression profiling highlighted that surface-sensing and protein secretion was also largely unaffected. However, ΔZtGT2 mutants constitutively overexpressed several transmembrane and secreted proteins, including an important LysM-domain chitin-binding virulence effector, Zt3LysM. ZtGT2 likely functions in the synthesis of a currently unknown, potentially minor but widespread, extracellular or outer cell wall polysaccharide which plays a key role in facilitating many interactions between plants and fungi by enabling hyphal growth on solid matrices
Common methodological pitfalls in ICI pneumonitis risk prediction studies
BackgroundPneumonitis is one of the most common adverse events induced by the use of immune checkpoint inhibitors (ICI), accounting for a 20% of all ICI-associated deaths. Despite numerous efforts to identify risk factors and develop predictive models, there is no clinically deployed risk prediction model for patient risk stratification or for guiding subsequent monitoring. We believe this is due to systemic suboptimal approaches in study designs and methodologies in the literature. The nature and prevalence of different methodological approaches has not been thoroughly examined in prior systematic reviews.MethodsThe PubMed, medRxiv and bioRxiv databases were used to identify studies that aimed at risk factor discovery and/or risk prediction model development for ICI-induced pneumonitis (ICI pneumonitis). Studies were then analysed to identify common methodological pitfalls and their contribution to the risk of bias, assessed using the QUIPS and PROBAST tools.ResultsThere were 51 manuscripts eligible for the review, with Japan-based studies over-represented, being nearly half (24/51) of all papers considered. Only 2/51 studies had a low risk of bias overall. Common bias-inducing practices included unclear diagnostic method or potential misdiagnosis, lack of multiple testing correction, the use of univariate analysis for selecting features for multivariable analysis, discretization of continuous variables, and inappropriate handling of missing values. Results from the risk model development studies were also likely to have been overoptimistic due to lack of holdout sets.ConclusionsStudies with low risk of bias in their methodology are lacking in the existing literature. High-quality risk factor identification and risk model development studies are urgently required by the community to give the best chance of them progressing into a clinically deployable risk prediction model. Recommendations and alternative approaches for reducing the risk of bias were also discussed to guide future studies
Chandra Cluster Cosmology Project III: Cosmological Parameter Constraints
Chandra observations of large samples of galaxy clusters detected in X-rays
by ROSAT provide a new, robust determination of the cluster mass functions at
low and high redshifts. Statistical and systematic errors are now sufficiently
small, and the redshift leverage sufficiently large for the mass function
evolution to be used as a useful growth of structure based dark energy probe.
In this paper, we present cosmological parameter constraints obtained from
Chandra observations of 36 clusters with =0.55 derived from 400deg^2 ROSAT
serendipitous survey and 49 brightest z=~0.05 clusters detected in the All-Sky
Survey. Evolution of the mass function between these redshifts requires
Omega_Lambda>0 with a ~5sigma significance, and constrains the dark energy
equation of state parameter to w0=-1.14+-0.21, assuming constant w and flat
universe. Cluster information also significantly improves constraints when
combined with other methods. Fitting our cluster data jointly with the latest
supernovae, WMAP, and baryonic acoustic oscillations measurements, we obtain
w0=-0.991+-0.045 (stat) +-0.039 (sys), a factor of 1.5 reduction in statistical
uncertainties, and nearly a factor of 2 improvement in systematics compared to
constraints that can be obtained without clusters. The joint analysis of these
four datasets puts a conservative upper limit on the masses of light neutrinos,
Sum m_nu<0.33 eV at 95% CL. We also present updated measurements of Omega_M*h
and sigma_8 from the low-redshift cluster mass function.Comment: ApJ, in press (Feb 10, 2009 issue
Current position of 5HT3 antagonists and the additional value of NK1 antagonists; a new class of antiemetics
The advent of the 5HT3 receptor antagonists (5HT3 antagonists) in the 1990s and the combination with dexamethasone has resulted in acute emesis protection in 70% of patients receiving highly emetogenic chemotherapy. Despite complete protection in the acute phase, however, 40% of patients as yet have symptoms in the delayed phase, 5HT3 antagonists and dexamethasone are only modestly effective in this delayed phase. Moreover, the antiemetic protection over repeated cycles is not sustained. Neurokinine 1 receptor antagonists (NK1 antagonists) belong to a new class of antiemetic agents that specifically target the NK1 receptor, which is involved in both the acute and, particularly, the delayed phase of emesis. Clinical studies have demonstrated that the addition of NK1 antagonists to dual therapy with a 5HT3 antagonist plus dexamethasone improves the acute emesis protection by a further 10-15%. In the delayed phase, the proportion of patients remaining free of emesis increases by even 20-30%. Since the effectiveness of this triplet combination was found to be sustained over six cycles of chemotherapy, the chance for an individual patient to remain completely protected during both the acute and the delayed phase over six chemotherapy cycles is nearly doubled
Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial
Background
Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy
Re-Annotation Is an Essential Step in Systems Biology Modeling of Functional Genomics Data
One motivation of systems biology research is to understand gene functions and interactions from functional genomics data such as that derived from microarrays. Up-to-date structural and functional annotations of genes are an essential foundation of systems biology modeling. We propose that the first essential step in any systems biology modeling of functional genomics data, especially for species with recently sequenced genomes, is gene structural and functional re-annotation. To demonstrate the impact of such re-annotation, we structurally and functionally re-annotated a microarray developed, and previously used, as a tool for disease research. We quantified the impact of this re-annotation on the array based on the total numbers of structural- and functional-annotations, the Gene Annotation Quality (GAQ) score, and canonical pathway coverage. We next quantified the impact of re-annotation on systems biology modeling using a previously published experiment that used this microarray. We show that re-annotation improves the quantity and quality of structural- and functional-annotations, allows a more comprehensive Gene Ontology based modeling, and improves pathway coverage for both the whole array and a differentially expressed mRNA subset. Our results also demonstrate that re-annotation can result in a different knowledge outcome derived from previous published research findings. We propose that, because of this, re-annotation should be considered to be an essential first step for deriving value from functional genomics data
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