92 research outputs found

    Ueber eine neue Synthese der Propionsäure

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    Spectroscopy of free radicals and radical containing entrance-channel complexes in superfluid helium nano-droplets

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    The spectroscopy of free radicals and radical containing entrance-channel complexes embedded in superfluid helium nano-droplets is reviewed. The collection of dopants inside individual droplets in the beam represents a micro-canonical ensemble, and as such each droplet may be considered an isolated cryo-reactor. The unique properties of the droplets, namely their low temperature (0.4 K) and fast cooling rates (1016\sim10^{16} K s1^{-1}) provides novel opportunities for the formation and high-resolution studies of molecular complexes containing one or more free radicals. The production methods of radicals are discussed in light of their applicability for embedding the radicals in helium droplets. The spectroscopic studies performed to date on molecular radicals and on entrance / exit-channel complexes of radicals with stable molecules are detailed. The observed complexes provide new information on the potential energy surfaces of several fundamental chemical reactions and on the intermolecular interactions present in open-shell systems. Prospects of further experiments of radicals embedded in helium droplets are discussed, especially the possibilities to prepare and study high-energy structures and their controlled manipulation, as well as the possibility of fundamental physics experiments.Comment: 25 pages, 12 figures, 4 tables (RevTeX

    Effects of boundary conditions on magnetization switching in kinetic Ising models of nanoscale ferromagnets

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    Magnetization switching in highly anisotropic single-domain ferromagnets has been previously shown to be qualitatively described by the droplet theory of metastable decay and simulations of two-dimensional kinetic Ising systems with periodic boundary conditions. In this article we consider the effects of boundary conditions on the switching phenomena. A rich range of behaviors is predicted by droplet theory: the specific mechanism by which switching occurs depends on the structure of the boundary, the particle size, the temperature, and the strength of the applied field. The theory predicts the existence of a peak in the switching field as a function of system size in both systems with periodic boundary conditions and in systems with boundaries. The size of the peak is strongly dependent on the boundary effects. It is generally reduced by open boundary conditions, and in some cases it disappears if the boundaries are too favorable towards nucleation. However, we also demonstrate conditions under which the peak remains discernible. This peak arises as a purely dynamic effect and is not related to the possible existence of multiple domains. We illustrate the predictions of droplet theory by Monte Carlo simulations of two-dimensional Ising systems with various system shapes and boundary conditions.Comment: RevTex, 48 pages, 13 figure

    Robust Inverse Modeling of Growing Season Net Ecosystem Exchange in a Mountainous Peatland: Influence of Distributional Assumptions on Estimated Parameters and Total Carbon Fluxes

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    While boreal lowland bogs have been extensively studied using the eddy‐covariance (EC) technique, less knowledge exists on mountainous peatlands. Hence, half‐hourly CO2 fluxes of an ombrotrophic peat bog in the Harz Mountains, Germany, were measured with the EC technique during a growing season with exceptionally dry weather spells. A common biophysical process model for net ecosystem exchange was used to describe measured CO2 fluxes and to fill data gaps. Model parameters and uncertainties were estimated by robust inverse modelling in a Bayesian framework using a population‐based Markov Chain Monte Carlo sampler. The focus of this study was on the correct statistical description of error, i.e. the differences between the measured and simulated carbon fluxes, and the influence of distributional assumptions on parameter estimates, cumulative carbon fluxes, and uncertainties. We tested the Gaussian, Laplace, and Student's t distribution as error models. The t‐distribution was identified as best error model by the deviance information criterion. Its use led to markedly different parameter estimates, a reduction of parameter uncertainty by about 40%, and, most importantly, to a 5% higher estimated cumulative CO2 uptake as compared to the commonly assumed Gaussian error distribution. As open‐path measurement systems have larger measurement error at high humidity, the standard deviation of the error was modeled as a function of measured vapor pressure deficit. Overall, this paper demonstrates the importance of critically assessing the influence of distributional assumptions on estimated model parameters and cumulative carbon fluxes between the land surface and the atmosphere

    Adaptor protein-2 sigma subunit mutations causing familial hypocalciuric hypercalcaemia type 3 (FHH3) demonstrate genotype-phenotype correlations, codon bias and dominant-negative effects

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    The adaptor protein-2 sigma subunit (AP2σ2) is pivotal for clathrin-mediated endocytosis of plasma membrane constituents such as the calcium-sensing receptor (CaSR). Mutations of the AP2σ2 Arg15 residue result in familial hypocalciuric hypercalcaemia type 3 (FHH3), a disorder of extracellular calcium (Ca(2+) o) homeostasis. To elucidate the role of AP2σ2 in Ca(2+) o regulation, we investigated 65 FHH probands, without other FHH-associated mutations, for AP2σ2 mutations, characterized their functional consequences and investigated the genetic mechanisms leading to FHH3. AP2σ2 mutations were identified in 17 probands, comprising 5 Arg15Cys, 4 Arg15His and 8 Arg15Leu mutations. A genotype-phenotype correlation was observed with the Arg15Leu mutation leading to marked hypercalcaemia. FHH3 probands harboured additional phenotypes such as cognitive dysfunction. All three FHH3-causing AP2σ2 mutations impaired CaSR signal transduction in a dominant-negative manner. Mutational bias was observed at the AP2σ2 Arg15 residue as other predicted missense substitutions (Arg15Gly, Arg15Pro and Arg15Ser), which also caused CaSR loss-of-function, were not detected in FHH probands, and these mutations were found to reduce the numbers of CaSR-expressing cells. FHH3 probands had significantly greater serum calcium (sCa) and magnesium (sMg) concentrations with reduced urinary calcium to creatinine clearance ratios (CCCR) in comparison with FHH1 probands with CaSR mutations, and a calculated index of sCa × sMg/100 × CCCR, which was ≥ 5.0, had a diagnostic sensitivity and specificity of 83 and 86%, respectively, for FHH3. Thus, our studies demonstrate AP2σ2 mutations to result in a more severe FHH phenotype with genotype-phenotype correlations, and a dominant-negative mechanism of action with mutational bias at the Arg15 residue

    Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

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    A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

    Expression profiles of switch-like genes accurately classify tissue and infectious disease phenotypes in model-based classification

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    <p>Abstract</p> <p>Background</p> <p>Large-scale compilation of gene expression microarray datasets across diverse biological phenotypes provided a means of gathering a priori knowledge in the form of identification and annotation of bimodal genes in the human and mouse genomes. These switch-like genes consist of 15% of known human genes, and are enriched with genes coding for extracellular and membrane proteins. It is of interest to determine the prediction potential of bimodal genes for class discovery in large-scale datasets.</p> <p>Results</p> <p>Use of a model-based clustering algorithm accurately classified more than 400 microarray samples into 19 different tissue types on the basis of bimodal gene expression. Bimodal expression patterns were also highly effective in differentiating between infectious diseases in model-based clustering of microarray data. Supervised classification with feature selection restricted to switch-like genes also recognized tissue specific and infectious disease specific signatures in independent test datasets reserved for validation. Determination of "on" and "off" states of switch-like genes in various tissues and diseases allowed for the identification of activated/deactivated pathways. Activated switch-like genes in neural, skeletal muscle and cardiac muscle tissue tend to have tissue-specific roles. A majority of activated genes in infectious disease are involved in processes related to the immune response.</p> <p>Conclusion</p> <p>Switch-like bimodal gene sets capture genome-wide signatures from microarray data in health and infectious disease. A subset of bimodal genes coding for extracellular and membrane proteins are associated with tissue specificity, indicating a potential role for them as biomarkers provided that expression is altered in the onset of disease. Furthermore, we provide evidence that bimodal genes are involved in temporally and spatially active mechanisms including tissue-specific functions and response of the immune system to invading pathogens.</p

    The Antimicrobial Peptide Histatin-5 Causes a Spatially Restricted Disruption on the Candida albicans Surface, Allowing Rapid Entry of the Peptide into the Cytoplasm

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    Antimicrobial peptides play an important role in host defense against microbial pathogens. Their high cationic charge and strong amphipathic structure allow them to bind to the anionic microbial cell membrane and disrupt the membrane bilayer by forming pores or channels. In contrast to the classical pore-forming peptides, studies on histatin-5 (Hst-5) have suggested that the peptide is transported into the cytoplasm of Candida albicans in a non-lytic manner, and cytoplasmic Hst-5 exerts its candicidal activities on various intracellular targets, consistent with its weak amphipathic structure. To understand how Hst-5 is internalized, we investigated the localization of FITC-conjugated Hst-5. We find that Hst-5 is internalized into the vacuole through receptor-mediated endocytosis at low extracellular Hst-5 concentrations, whereas under higher physiological concentrations, Hst-5 is translocated into the cytoplasm through a mechanism that requires a high cationic charge on Hst-5. At intermediate concentrations, two cell populations with distinct Hst-5 localizations were observed. By cell sorting, we show that cells with vacuolar localization of Hst-5 survived, while none of the cells with cytoplasmic Hst-5 formed colonies. Surprisingly, extracellular Hst-5, upon cell surface binding, induces a perturbation on the cell surface, as visualized by an immediate and rapid internalization of Hst-5 and propidium iodide or rhodamine B into the cytoplasm from the site using time-lapse microscopy, and a concurrent rapid expansion of the vacuole. Thus, the formation of a spatially restricted site in the plasma membrane causes the initial injury to C. albicans and offers a mechanism for its internalization into the cytoplasm. Our study suggests that, unlike classical channel-forming antimicrobial peptides, action of Hst-5 requires an energized membrane and causes localized disruptions on the plasma membrane of the yeast. This mechanism of cell membrane disruption may provide species-specific killing with minimal damage to microflora and the host and may be used by many other antimicrobial peptides

    Molecules with ALMA at planet-forming scales (MAPS). IV. Emission surfaces and vertical distribution of molecules

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    The Molecules with ALMA at Planet-forming Scales (MAPS) Large Program provides a unique opportunity to study the vertical distribution of gas, chemistry, and temperature in the protoplanetary disks around IM Lup, GM Aur, AS 209, HD 163296, and MWC 480. By using the asymmetry of molecular line emission relative to the disk major axis, we infer the emission height (z) above the midplane as a function of radius (r). Using this method, we measure emitting surfaces for a suite of CO isotopologues, HCN, and C2H. We find that 12CO emission traces the most elevated regions with z/r > 0.3, while emission from the less abundant 13CO and C18O probes deeper into the disk at altitudes of z/r ≲ 0.2. C2H and HCN have lower opacities and signal-to-noise ratios, making surface fitting more difficult, and could only be reliably constrained in AS 209, HD 163296, and MWC 480, with z/r ≲ 0.1, i.e., relatively close to the planet-forming midplanes. We determine peak brightness temperatures of the optically thick CO isotopologues and use these to trace 2D disk temperature structures. Several CO temperature profiles and emission surfaces show dips in temperature or vertical height, some of which are associated with gaps and rings in line and/or continuum emission. These substructures may be due to local changes in CO column density, gas surface density, or gas temperatures, and detailed thermochemical models are necessary to better constrain their origins and relate the chemical compositions of elevated disk layers with those of planet-forming material in disk midplanes. This paper is part of the MAPS special issue of the Astrophysical Journal Supplement. © 2021. The American Astronomical Society. All rights reserved.Immediate accessThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
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