Role of the exchange and correlation potential into calculating the x-ray absorption spectra of half-metallic alloys: the case of Mn and Cu K-edge XANES in Cu2_2MnM (M = Al, Sn, In) Heusler alloys

This work reports a theoretical study of the x-ray absorption near-edge structure spectra at both the Cu and the Mn K-edge in several Cu$_2$MnM (M= Al, Sn and In) Heusler alloys. Our results show that {\it ab-initio} single-channel multiple-scattering calculations are able of reproducing the experimental spectra. Moreover, an extensive discussion is presented concerning the role of the final state potential needed to reproduce the experimental data of these half-metallic alloys. In particular, the effects of the cluster-size and of the exchange and correlation potential needed in reproducing all the experimental XANES features are discussed.Comment: 15 pages, 5 figure

Feasible combinatorial matrix theory

We show that the well-known Konig's Min-Max Theorem (KMM), a fundamental result in combinatorial matrix theory, can be proven in the first order theory \LA with induction restricted to $\Sigma_1^B$ formulas. This is an improvement over the standard textbook proof of KMM which requires $\Pi_2^B$ induction, and hence does not yield feasible proofs --- while our new approach does. \LA is a weak theory that essentially captures the ring properties of matrices; however, equipped with $\Sigma_1^B$ induction \LA is capable of proving KMM, and a host of other combinatorial properties such as Menger's, Hall's and Dilworth's Theorems. Therefore, our result formalizes Min-Max type of reasoning within a feasible framework

Preparation and structural properties of thin films and multilayers of the Heusler compounds Cu2MnAl, Co2MnSn, Co2MnSi and Co2MnGe

We report on the preparation of thin films and multilayers of the intermetallic Heusler compound CuMnAl, Co2MnSn, Co2MnSi and Co2MnGe by rf-sputtering on MgO and Al2O3 substrates. Cu2MnAl can be grown epitaxially with (100)-orientation on MgO (100) and in (110)-orientation on Al2O3 a-plane. The Co based Heusler alloys need metallic seedlayers to induce high quality textured growth. We also have prepared multilayers with smooth interfaces by combining the Heusler compounds with Au and V. An analysis of the ferromagnetic saturation magnetization of the films indicates that the Cu2MnAl-compound tends to grow in the disordered B2-type structure whereas the Co-based Heusler alloy thin films grow in the ordered L21 structure. All multilayers with thin layers of the Heusler compounds exhibit a definitely reduced ferromagnetic magnetization indicating substantial disorder and intermixing at the interfaces.Comment: 21 pages, 8 figure

Magnetic phase separation in ordered alloys

We present a lattice model to study the equilibrium phase diagram of ordered alloys with one magnetic component that exhibits a low temperature phase separation between paramagnetic and ferromagnetic phases. The model is constructed from the experimental facts observed in Cu$_{3-x}$AlMn$_{x}$ and it includes coupling between configurational and magnetic degrees of freedom which are appropriated for reproducing the low temperature miscibility gap. The essential ingredient for the occurrence of such a coexistence region is the development of ferromagnetic order induced by the long-range atomic order of the magnetic component. A comparative study of both mean-field and Monte Carlo solutions is presented. Moreover, the model may enable the study of the structure of the ferromagnetic domains embedded in the non-magnetic matrix. This is relevant in relation to phenomena such as magnetoresistance and paramagnetism.Comment: 12 pages, 11 figures, accepted in Phys. Rev.

Upwelling events, coastal offshore exchange, links to biogeochemical processes - Highlights from the Baltic Sea Sciences Congress at Rostock University, Germany, 19-22 March 2007

The Baltic Sea Science Congress was held at Rostock University, Germany, from 19 to 22 March 2007. In the session entitled"Upwelling events, coastal offshore exchange, links to biogeochemical processes" 20 presentations were given,including 7 talks and 13 posters related to the theme of the session.This paper summarises new findings of the upwelling-related studies reported in the session. It deals with investigationsbased on the use of in situ and remote sensing measurements as well as numerical modelling tools. The biogeochemicalimplications of upwelling are also discussed.Our knowledge of the fine structure and dynamic considerations of upwelling has increased in recent decades with the advent ofhigh-resolution modern measurement techniques and modelling studies. The forcing and the overall structure, duration and intensity ofupwelling events are understood quite well. However, the quantification of related transports and the contribution to the overall mixingof upwelling requires further research. Furthermore, our knowledge of the links between upwelling and biogeochemical processes is stillincomplete. Numerical modelling has advanced to the extent that horizontal resolutions of c. 0.5 nautical miles can now be applied,which allows the complete spectrum of meso-scale features to be described. Even the development of filaments can be describedrealistically in comparison with high-resolution satellite data.But the effect of upwelling at a basin scale and possible changes under changing climatic conditions remain open questions

Studies of viomycin, an anti-tuberculosis antibiotic: Copper(II) coordination, DNA degradation and the impact on delta ribozyme cleavage activity

Viomycin is a basic peptide antibiotic, which is among the most effective agents against multidrug-resistant tuberculosis. In this paper we provide the characteristics of its acid base properties, coordination preferences towards the Cu(II) ions, as well as the reactivity of the resulting complexes against plasmid DNA and HDV ribozyme. Careful coordination studies throughout the wide pH range allow for the characterisation of all the Cu(II)-viomycin complex species. The assignment of proton chemical shifts was achieved by NMR experiments, while the DTF level of theory was applied to support molecular structures of the studied complexes. The experiments with the plasmid DNA reveal that at the physiological levels of hydrogen peroxide the Cu(II)-viomycin complex is more aggressive against DNA than uncomplexed metal ions. Moreover, the degradation of DNA by viomycin can be carried out without the presence of transition metal ions. In the studies of antigenomic delta ribozyme catalytic activity, viomycin and its complex are shown to modulate the ribozyme functioning. The molecular modelling approach allows the indication of two different locations of viomycin binding sites to the ribozyme

Mitochondrial targeting adaptation of the hominoid-specific glutamate dehydrogenase driven by positive Darwinian selection

Many new gene copies emerged by gene duplication in hominoids, but little is known with respect to their functional evolution. Glutamate dehydrogenase (GLUD) is an enzyme central to the glutamate and energy metabolism of the cell. In addition to the single, GLUD-encoding gene present in all mammals (GLUD1), humans and apes acquired a second GLUD gene (GLUD2) through retroduplication of GLUD1, which codes for an enzyme with unique, potentially brain-adapted properties. Here we show that whereas the GLUD1 parental protein localizes to mitochondria and the cytoplasm, GLUD2 is specifically targeted to mitochondria. Using evolutionary analysis and resurrected ancestral protein variants, we demonstrate that the enhanced mitochondrial targeting specificity of GLUD2 is due to a single positively selected glutamic acid-to-lysine substitution, which was fixed in the N-terminal mitochondrial targeting sequence (MTS) of GLUD2 soon after the duplication event in the hominoid ancestor ~18–25 million years ago. This MTS substitution arose in parallel with two crucial adaptive amino acid changes in the enzyme and likely contributed to the functional adaptation of GLUD2 to the glutamate metabolism of the hominoid brain and other tissues. We suggest that rapid, selectively driven subcellular adaptation, as exemplified by GLUD2, represents a common route underlying the emergence of new gene functions

Activation of Type 1 Cannabinoid Receptor (CB1R) promotes neurogenesis in murine subventricular zone cell cultures

The endocannabinoid system has been implicated in the modulation of adult neurogenesis. Here, we describe the effect of type 1 cannabinoid receptor (CB1R) activation on self-renewal, proliferation and neuronal differentiation in mouse neonatal subventricular zone (SVZ) stem/progenitor cell cultures. Expression of CB1R was detected in SVZ-derived immature cells (Nestin-positive), neurons and astrocytes. Stimulation of the CB1R by (R)-(+)-Methanandamide (R-m-AEA) increased self-renewal of SVZ cells, as assessed by counting the number of secondary neurospheres and the number of Sox2+/+ cell pairs, an effect blocked by Notch pathway inhibition. Moreover, R-m-AEA treatment for 48 h, increased proliferation as assessed by BrdU incorporation assay, an effect mediated by activation of MAPK-ERK and AKT pathways. Surprisingly, stimulation of CB1R by R-m-AEA also promoted neuronal differentiation (without affecting glial differentiation), at 7 days, as shown by counting the number of NeuN-positive neurons in the cultures. Moreover, by monitoring intracellular calcium concentrations ([Ca2+](i)) in single cells following KCl and histamine stimuli, a method that allows the functional evaluation of neuronal differentiation, we observed an increase in neuronal-like cells. This proneurogenic effect was blocked when SVZ cells were co-incubated with R-m-AEA and the CB1R antagonist AM 251, for 7 days, thus indicating that this effect involves CB1R activation. In accordance with an effect on neuronal differentiation and maturation, R-m-AEA also increased neurite growth, as evaluated by quantifying and measuring the number of MAP2-positive processes. Taken together, these results demonstrate that CB1R activation induces proliferation, self-renewal and neuronal differentiation from mouse neonatal SVZ cell cultures.Fundacao para a Ciencia e a Tecnologia - Portugal [POCTI/SAU-NEU/68465/2006, PTDC/SAU-NEU/104415/2008, PTDC/SAU-NEU/101783/2008, POCTI/SAU-NEU/110838/2009]; Fundacao Calouste Gulbenkian [96542]; Fundacao para a Ciencia e Tecnologiainfo:eu-repo/semantics/publishedVersio

CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis

BACKGROUND: Transthyretin amyloidosis, also called ATTR amyloidosis, is a life-threatening disease characterized by progressive accumulation of misfolded transthyretin (TTR) protein in tissues, predominantly the nerves and heart. NTLA-2001 is an in vivo gene-editing therapeutic agent that is designed to treat ATTR amyloidosis by reducing the concentration of TTR in serum. It is based on the clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease (CRISPR-Cas9) system and comprises a lipid nanoparticle encapsulating messenger RNA for Cas9 protein and a single guide RNA targeting TTR. METHODS: After conducting preclinical in vitro and in vivo studies, we evaluated the safety and pharmacodynamic effects of single escalating doses of NTLA-2001 in six patients with hereditary ATTR amyloidosis with polyneuropathy, three in each of the two initial dose groups (0.1 mg per kilogram and 0.3 mg per kilogram), within an ongoing phase 1 clinical study. RESULTS: Preclinical studies showed durable knockout of TTR after a single dose. Serial assessments of safety during the first 28 days after infusion in patients revealed few adverse events, and those that did occur were mild in grade. Dose-dependent pharmacodynamic effects were observed. At day 28, the mean reduction from baseline in serum TTR protein concentration was 52% (range, 47 to 56) in the group that received a dose of 0.1 mg per kilogram and was 87% (range, 80 to 96) in the group that received a dose of 0.3 mg per kilogram. CONCLUSIONS: In a small group of patients with hereditary ATTR amyloidosis with polyneuropathy, administration of NTLA-2001 was associated with only mild adverse events and led to decreases in serum TTR protein concentrations through targeted knockout of TTR. (Funded by Intellia Therapeutics and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT04601051. opens in new tab.