Molecular dynamics study of taxadiene synthase catalysis

Molecular dynamics (MD) simulations have been performed to study the dynamic behavior of noncovalent enzyme carbocation complexes involved in the cyclization of geranylgeranyl diphosphate to taxadiene catalyzed by taxadiene synthase (TXS). Taxadiene and the observed four side products originate from the deprotonation of carbocation intermediates. The MD simulations of the TXS carbocation complexes provide insights into potential deprotonation mechanisms of such carbocations. The MD results do not support a previous hypothesis that carbocation tumbling is a key factor in the deprotonation of the carbocations by pyrophosphate. Instead water bridges are identified which may allow the formation of side products via multiple proton transfer reactions. A novel reaction path for taxadiene formation is proposed on the basis of the simulations

Strain and composition dependence of the orbital polarization in nickelate superlattices

A combined analysis of x-ray absorption and resonant reflectivity data was used to obtain the orbital polarization profiles of superlattices composed of four-unit-cell-thick layers of metallic LaNiO3 and layers of insulating RXO3 (R=La, Gd, Dy and X=Al, Ga, Sc), grown on substrates that impose either compressive or tensile strain. This superlattice geometry allowed us to partly separate the influence of epitaxial strain from interfacial effects controlled by the chemical composition of the insulating blocking layers. Our quantitative analysis reveal orbital polarizations up to 25%. We further show that strain is the most effective control parameter, whereas the influence of the chemical composition of the blocking layers is comparatively small.Comment: 9 pages, 8 figure

Concurrent axon and myelin destruction differentiates X-linked adrenoleukodystrophy from multiple sclerosis

Cerebral disease manifestation occurs in about two thirds of males with X-linked adrenoleukodystrophy (CALD) and is fatally progressive if left untreated. Early histopathologic studies categorized CALD as an inflammatory demyelinating disease, which led to repeated comparisons to multiple sclerosis (MS). The aim of this study was to revisit the relationship between axonal damage and myelin loss in CALD. We applied novel immunohistochemical tools to investigate axonal damage, myelin loss and myelin repair in autopsy brain tissue of eight CALD and 25 MS patients. We found extensive and severe acute axonal damage in CALD already in prelesional areas defined by microglia loss and relative myelin preservation. In contrast to MS, we did not observe selective phagocytosis of myelin, but a concomitant decay of the entire axon-myelin unit in all CALD lesion stages. Using a novel marker protein for actively remyelinating oligodendrocytes, breast carcinoma-amplified sequence (BCAS) 1, we show that repair pathways are activated in oligodendrocytes in CALD. Regenerating cells, however, were affected by the ongoing disease process. We provide evidence that—in contrast to MS—selective myelin phagocytosis is not characteristic of CALD. On the contrary, our data indicate that acute axonal injury and permanent axonal loss are thus far underestimated features of the disease that must come into focus in our search for biomarkers and novel therapeutic approaches

Differential systems associated with tableaux over Lie algebras

We give an account of the construction of exterior differential systems based on the notion of tableaux over Lie algebras as developed in [Comm. Anal. Geom 14 (2006), 475-496; math.DG/0412169]. The definition of a tableau over a Lie algebra is revisited and extended in the light of the formalism of the Spencer cohomology; the question of involutiveness for the associated systems and their prolongations is addressed; examples are discussed.Comment: 16 pages; to appear in: "Symmetries and Overdetermined Systems of Partial Differential Equations" (M. Eastwood and W. Miller, Jr., eds.), IMA Volumes in Mathematics and Its Applications, Springer-Verlag, New Yor

Equilibrium susceptibilities of superparamagnets: longitudinal & transverse, quantum & classical

The equilibrium susceptibility of uniaxial paramagnets is studied in a unified framework which permits to connect traditional results of the theory of quantum paramagnets, \Sm=1/2, 1, 3/2, ..., with molecular magnetic clusters, \Sm\sim5, 10, 20, all the way up, \Sm=30, 50, 100,... to the theory of classical superparamagnets. This is done using standard tools of quantum statistical mechanics and linear response theory (the Kubo correlator formalism). Several features of the temperature dependence of the susceptibility curves (crossovers, peaks, deviations from Curie law) are studied and their scalings with \Sm identified and characterized. Both the longitudinal and transverse susceptibilities are discussed, as well as the response of the ensemble with anisotropy axes oriented at random. For the latter case a simple approximate formula is derived too, and its range of validity assessed, so it could be used in modelization of experiments.Comment: 32 pages, 5 figures. Submitted to J.Phys.Condens.Matte

Thermodynamic analysis of the Quantum Critical behavior of Ce-lattice compounds

A systematic analysis of low temperature magnetic phase diagrams of Ce compounds is performed in order to recognize the thermodynamic conditions to be fulfilled by those systems to reach a quantum critical regime and, alternatively, to identify other kinds of low temperature behaviors. Based on specific heat ($C_m$) and entropy ($S_m$) results, three different types of phase diagrams are recognized: i) with the entropy involved into the ordered phase ($S_{MO}$) decreasing proportionally to the ordering temperature ($T_{MO}$), ii) those showing a transference of degrees of freedom from the ordered phase to a non-magnetic component, with their $C_m(T_{MO})$ jump ($\Delta C_m$) vanishing at finite temperature, and iii) those ending in a critical point at finite temperature because their $\Delta C_m$ do not decrease with $T_{MO}$ producing an entropy accumulation at low temperature. Only those systems belonging to the first case, i.e. with $S_{MO}\to 0$ as $T_{MO}\to 0$, can be regarded as candidates for quantum critical behavior. Their magnetic phase boundaries deviate from the classical negative curvature below $T\approx 2.5$\,K, denouncing frequent misleading extrapolations down to T=0. Different characteristic concentrations are recognized and analyzed for Ce-ligand alloyed systems. Particularly, a pre-critical region is identified, where the nature of the magnetic transition undergoes significant modifications, with its $\partial C_m/\partial T$ discontinuity strongly affected by magnetic field and showing an increasing remnant entropy at $T\to 0$. Physical constraints arising from the third law at $T\to 0$ are discussed and recognized from experimental results

Orbital reflectometry

The occupation of d-orbitals controls the magnitude and anisotropy of the inter-atomic electron transfer in transition metal oxides and hence exerts a key influence on their chemical bonding and physical properties. Atomic-scale modulations of the orbital occupation at surfaces and interfaces are believed to be responsible for massive variations of the magnetic and transport properties, but could thus far not be probed in a quantitative manner. Here we show that it is possible to derive quantitative, spatially resolved orbital polarization profiles from soft x-ray reflectivity data, without resorting to model calculations. We demonstrate that the method is sensitive enough to resolve differences of 3 % in the occupation of Ni e_g orbitals in adjacent atomic layers of a LaNiO3-LaAlO3 superlattice, in good agreement with ab-initio electronic-structure calculations. The possibility to quantitatively correlate theory and experiment on the atomic scale opens up many new perspectives for orbital physics in d-electron materials

Institutional legacies and HRM: similarities and differences in HRM practices in Portugal and Mozambique

This is a study of institutional change and continuity, comparing the trajectories followed by Mozambique and its formal colonial power Portugal in HRM, based on two surveys of firm level practices. The colonial power sought to extend the institutions of the metropole in the closing years of its rule, and despite all the adjustments and shocks that have accompanied Mozambique’s post-independence years, the country continues to retain institutional features and associated practices from the past. This suggests that there is a post-colonial impact on human resource management. The implications for HRM theory are that ambitious attempts at institutional substitution may have less dramatic effects than is commonly assumed. Indeed, we encountered remarkable similarities between the two countries in HRM practices, implying that features of supposedly fluid or less mature institutional frameworks (whether in Africa or the Mediterranean world) may be sustained for protracted periods of time, pressures to reform notwithstanding. This highlights the complexities of continuities which transcend formal rules; as post-colonial theories alert us, informal conventions and embedded discourse may result in the persistence of informal power and subordination, despite political and legal changes

DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology