352 research outputs found

    Testing Nonlinear New Economic Geography Models

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    We test a New Economic Geography (NEG) model for U.S. counties, employing a new strategy that allows us to bring the full NEG model to the data, and to assess selected elements of this model separately. We find no empirical support for the full NEG model. Regional wages in the U.S. do not respond to local wage shocks in the way predicted by the model. We show that the main reason for this is that the model does not predict either the migration patterns induced by local wage shocks or the repercussions of this migration for regional wages correctly.New economic geography, spatial econometrics

    Functional characterization of extraocular muscle in transgenic mouse models

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    Extraocular muscles (EOMs) are among the fastest and most fatigue resistant skeletal muscles; they are categorized as a separate group of muscles or ‘allotype’ since they represent a unique group of highly specialized muscles anatomically and physiologically different from other skeletal muscles. The distinct origin and innervation of EOMs are probably responsible for their different gene and protein expression. This also applies for the excitation–contraction coupling (ECC) and the calcium handling in EOMs. The main goal of this thesis is to establish methods to study the ECC in mouse EOMs and apply these new techniques on different mouse models. Calcium is an ubiquitous second messenger mediating numerous physiological processes, including muscle contraction and neuronal excitability. Ca2+ is stored in the ER/SR and is released into the cytoplasm via the opening of intracellular inositol trisphosphate receptor and ryanodine receptor calcium channels. Whereas in skeletal muscle, isoform 1 of the RYR is the main channel mediating calcium release from the SR leading to muscle contraction, the function of ubiquitously expressed ryanodine receptor 3 (RyR3) is far from clear. The previous finding of our group, that RyR3 is highly expressed in EOMs versus limb muscles (Sekulic-Jablanovic et al., 2015) is the basis of the first paper entitled “Extraocular muscle function is impaired in ryr3−/− mice”. By using the RyR3 KO mouse we were able to show that RyR3 is an essential factor for normal vision, which is the first real functional role of this channel. In detail, the loss of RyR3 reduced the peak force and altered the twitch kinetic of isolated EOMs. Additionally, we found altered calcium transient kinetic in isolated single EOM fibers. Mutations in the RYR1 gene are associated with neuromuscular disorders and patients with recessive mutations are severely affected and characteristically display ptosis and/or ophthalmoplegia. Previously we constructed a compound heterozygous RyR1p.Q1970fsX16+p.A4329D (DKI) mutant mice based on a patient biopsy (Klein et al., 2012) and characterized the skeletal muscles (Elbaz et al., 2019b; a). In order to gain insight into the mechanism leading to extraocular muscle involvement, we investigated the biochemical, structural and physiological properties of EOMs from this mouse model. We also investigated the properties of EOMS of heterozygous single mutation carriers as well as mice carrying the homozygous mutation. These studies constitute the second paper entitled “Molecular basis of impaired extraocular muscle function in a mouse model of congenital myopathy due to compound heterozygous RYR1 mutations”. In this paper we were able to show a significant reduction in the ex vivo force of the DKI mouse, while the other lines do not show any changes. These findings were constant with a reduction in the peak calcium transients and in several ECC involved proteins. Interestingly, we also found a tremendous reduction in the specific MyHC-EO isoform. To sum it up, our results shows that the combination of a reduced content of ryanodine and dihydropyridine receptors, changes in the calcium release units and reduced MyHC-EO leads to impaired vision. The methods and findings in this thesis will be the start of further investigation into EOM specific disorders or neuromuscular disorders which where EOMs are spared or heavy affected

    Double ionization of a three-electron atom: Spin correlation effects

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    We study the effects of spin degrees of freedom and wave function symmetries on double ionization in three-electron systems. Each electron is assigned one spatial degree of freedom. The resulting three-dimensional Schr\"odinger equation is integrated numerically using grid-based Fourier transforms. We reveal three-electron effects on the double ionization yield by comparing signals for different ionization channels. We explain our findings by the existence of fundamental differences between three-electronic and truly two-electronic spin-resolved ionization schemes. We find, for instance, that double ionization from a three-electron system is dominated by electrons that have the opposite spin

    Restricted space ab initio models for double ionization by strong laser pulses

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    Double electron ionisation process occurs when an intense laser pulse interacts with atoms or molecules. Exact {\it ab initio} numerical simulation of such a situation is extremely computer resources demanding, thus often one is forced to apply reduced dimensionality models to get insight into the physics of the process. The performance of several algorithms for simulating double electron ionization by strong femtosecond laser pulses are studied. The obtained ionization yields and the momentum distributions of the released electrons are compared, and the effects of the model dimensionality on the ionization dynamics discussed

    Role of the JP45-Calsequestrin Complex on Calcium Entry in Slow Twitch Skeletal Muscles

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    We exploited a variety of mouse models to assess the roles of JP45-CASQ1 (CASQ, calsequestrin) and JP45-CASQ2 on calcium entry in slow twitch muscles. In flexor digitorum brevis (FDB) fibers isolated from JP45-CASQ1-CASQ2 triple KO mice, calcium transients induced by tetanic stimulation rely on calcium entry via La3+- and nifedipine-sensitive calcium channels. The comparison of excitation-coupled calcium entry (ECCE) between FDB fibers from WT, JP45KO, CASQ1KO, CASQ2KO, JP45-CASQ1 double KO, JP45-CASQ2 double KO, and JP45-CASQ1-CASQ2 triple KO shows that ECCE enhancement requires ablation of both CASQs and JP45. Calcium entry activated by ablation of both JP45-CASQ1 and JP45-CASQ2 complexes supports tetanic force development in slow twitch soleus muscles. In addition, we show that CASQs interact with JP45 at Ca2+ concentrations similar to those present in the lumen of the sarcoplasmic reticulum at rest, whereas Ca2+ concentrations similar to those present in the SR lumen after depolarization-induced calcium release cause the dissociation of JP45 from CASQs. Our results show that the complex JP45-CASQs is a negative regulator of ECCE and that tetanic force development in slow twitch muscles is supported by the dynamic interaction between JP45 and CASQs

    Iron-based pre-catalyst supported on polyformamidine for C-C bond formation

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    Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG geförderten) Allianz- bzw. Nationallizenz frei zugĂ€nglich.This publication is with permission of the rights owner freely accessible due to an Alliance licence and a national licence (funded by the DFG, German Research Foundation) respectively.In the present study the incorporation of iron into an organic polymer, composed of formamidine subunits [R–N[double bond, length as m-dash]C(H)–NH–R], has been examined. The catalytic ability of the recyclable material was investigated in the iron-catalyzed formation of C–C bonds. After optimization of the reaction conditions, excellent yields and chemoselectivities were feasible.DFG, EXC 314, Unifying Concepts in Catalysi

    Quantitative proteomic analysis of skeletal muscles from wild type and transgenic mice carrying recessive Ryr1 mutations linked to congenital myopathies

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    Skeletal muscle is a highly structured and differentiated tissue responsible for voluntary movement and metabolic regulation. Muscles however, are heterogeneous and depending on their location, speed of contraction, fatiguability and function, can be broadly subdivided into fast and slow twitch as well as subspecialized muscles, with each group expressing common as well as specific proteins. Congenital myopathies are a group of non-inflammatory non-dystrophic muscle diseases caused by mutations in a number of genes, leading to a weak muscle phenotype. In most cases specific muscles types are affected, with preferential involvement of fast twitch muscles as well as extraocular and facial muscles. Here we performed relative and absolute quantitative proteomic analysis of EDL, soleus and extraocular muscles from wild type and transgenic mice carrying compound heterozygous mutations in Ryr1 identified in a patient with a severe congenital myopathy. Our quantitative proteomic study shows that recessive Ryr1 mutations not only decrease the content of RyR1 protein in muscle, but also impact the content of many other proteins; in addition, we provide important insight into the pathological mechanism of congenital myopathies linked to mutations in other genes encoding components of the excitation contraction coupling molecular complex

    Singular continuous spectra in a pseudo-integrable billiard

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    The pseudo-integrable barrier billiard invented by Hannay and McCraw [J. Phys. A 23, 887 (1990)] -- rectangular billiard with line-segment barrier placed on a symmetry axis -- is generalized. It is proven that the flow on invariant surfaces of genus two exhibits a singular continuous spectral component.Comment: 4 pages, 2 figure

    Elliptic Quantum Billiard

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    The exact and semiclassical quantum mechanics of the elliptic billiard is investigated. The classical system is integrable and exhibits a separatrix, dividing the phasespace into regions of oscillatory and rotational motion. The classical separability carries over to quantum mechanics, and the Schr\"odinger equation is shown to be equivalent to the spheroidal wave equation. The quantum eigenvalues show a clear pattern when transformed into the classical action space. The implication of the separatrix on the wave functions is illustrated. A uniform WKB quantization taking into account complex orbits is shown to be adequate for the semiclassical quantization in the presence of a separatrix. The pattern of states in classical action space is nicely explained by this quantization procedure. We extract an effective Maslov phase varying smoothly on the energy surface, which is used to modify the Berry-Tabor trace formula, resulting in a summation over non-periodic orbits. This modified trace formula produces the correct number of states, even close to the separatrix. The Fourier transform of the density of states is explained in terms of classical orbits, and the amplitude and form of the different kinds of peaks is analytically calculated.Comment: 33 pages, Latex2e, 19 figures,macros: epsfig, amssymb, amstext, submitted to Annals of Physic

    Polymer transport in random flow

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    The dynamics of polymers in a random smooth flow is investigated in the framework of the Hookean dumbbell model. The analytical expression of the time-dependent probability density function of polymer elongation is derived explicitly for a Gaussian, rapidly changing flow. When polymers are in the coiled state the pdf reaches a stationary state characterized by power-law tails both for small and large arguments compared to the equilibrium length. The characteristic relaxation time is computed as a function of the Weissenberg number. In the stretched state the pdf is unstationary and exhibits multiscaling. Numerical simulations for the two-dimensional Navier-Stokes flow confirm the relevance of theoretical results obtained for the delta-correlated model.Comment: 28 pages, 6 figure
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