203 research outputs found
Taxation and capital structure choice: evidence from a panel of German multinationals
This paper analyzes the impact of taxes and lending conditions on the financial structure of multinationals? foreign affiliates. The empirical analysis employs a large panel of affiliates of German multinationals in 26 countries in the period from 1996 until 2003. In accordance with the theoretical predictions, the effect of local taxes on leverage is positive for both types of debt. Moreover, while adverse local credit market conditions are found to reduce external borrowing, internal debt is increasing, supporting the view that the two channels of debt finance are substitutes. --Corporate Income Tax,Multinationals,Capital Structure,Firm-Level Data
The Impact of Thin-Capitalization Rules on Multinationals’ Financing and Investment Decisions
This paper analyzes the role of Thin-Capitalization rules for capital structure choice and investment decisions of multinationals. A theoretical analysis shows that the imposition of such rules tends to affect not only the leverage and the level of investment but also their tax-sensitivity. An empirical investigation of leverage and investment reported for affiliates of German multinationals in 24 countries in the period between 1996 and 2004 offers some support for the theoretical predictions. While Thin-Capitalization rules are found to be effective in restricting debt finance, investment is found to be more sensitive to taxes if debt finance is restricted.corporate income tax, multinationals, leverage, Thin-Capitalization rules, firm-level data
The impact of thin-capitalization rules on multinationals' financing and investment decisions
This paper analyzes the effectiveness of thin-capitalization rules in preventing debt finance by intercompany loans and explores their consequences for corporate decisions. A theoretical discussion emphasizes that limitations of the deduction of interest owed to foreign affiliates would not only affect multinationals' capital structure choice but also investment. An empirical investigation exploits a large firm-level panel dataset of multinationals in order to analyze the impact of thin-capitalization rules on capital structure choice and investment in the OECD and some further European countries in the time period between 1996 and 2004. The results indicate that thin-capitalization rules are effective in curbing tax planning via intercompany loans. However, investment is found to be adversely affected. --Corporate Income Tax,Multinationals,Leverage,Thin-Capitalization Rules,Firm-Level Data
A model-based theory on the origin of downbeat nystagmus
The pathomechanism of downbeat nystagmus (DBN), an ocular motor sign typical for vestibulo-cerebellar lesions, remains unclear. Previous hypotheses conjectured various deficits such as an imbalance of central vertical vestibular or smooth pursuit pathways to be causative for the generation of spontaneous upward drift. However, none of the previous theories explains the full range of ocular motor deficits associated with DBN, i.e., impaired vertical smooth pursuit (SP), gaze evoked nystagmus, and gravity dependence of the upward drift. We propose a new hypothesis, which explains the ocular motor signs of DBN by damage of the inhibitory vertical gaze-velocity sensitive Purkinje cells (PCs) in the cerebellar flocculus (FL). These PCs show spontaneous activity and a physiological asymmetry in that most of them exhibit downward on-directions. Accordingly, a loss of vertical floccular PCs will lead to disinhibition of their brainstem target neurons and, consequently, to spontaneous upward drift, i.e., DBN. Since the FL is involved in generation and control of SP and gaze holding, a single lesion, e.g., damage to vertical floccular PCs, may also explain the associated ocular motor deficits. To test our hypothesis, we developed a computational model of vertical eye movements based on known ocular motor anatomy and physiology, which illustrates how cortical, cerebellar, and brainstem regions interact to generate the range of vertical eye movements seen in healthy subjects. Model simulation of the effect of extensive loss of floccular PCs resulted in ocular motor features typically associated with cerebellar DBN: (1) spontaneous upward drift due to decreased spontaneous PC activity, (2) gaze evoked nystagmus corresponding to failure of the cerebellar loop supporting neural integrator function, (3) asymmetric vertical SP deficit due to low gain and asymmetric attenuation of PC firing, and (4) gravity-dependence of DBN caused by an interaction of otolith-ocular pathways with impaired neural integrator functio
An Information-Theoretic Approach for Evaluating Probabilistic Tuning Functions of Single Neurons
Neuronal tuning functions can be expressed by the conditional probability of observing a spike given any combination of explanatory variables. However, accurately determining such probabilistic tuning functions from experimental data poses several challenges such as finding the right combination of explanatory variables and determining their proper neuronal latencies. Here we present a novel approach of estimating and evaluating such probabilistic tuning functions, which offers a solution for these problems. By maximizing the mutual information between the probability distributions of spike occurrence and the variables, their neuronal latency can be estimated, and the dependence of neuronal activity on different combinations of variables can be measured. This method was used to analyze neuronal activity in cortical area MSTd in terms of dependence on signals related to eye and retinal image movement. Comparison with conventional feature detection and regression analysis techniques shows that our method offers distinct advantages, if the dependence does not match the regression model
qPCR in gastrointestinal stromal tumors: Evaluation of reference genes and expression analysis of KIT and the alternative receptor tyrosine kinases FLT3, CSF1-R, PDGFRB, MET and AXL
<p>Abstract</p> <p>Background</p> <p>Gastrointestinal stromal tumors (GIST) represent the most common mesenchymal tumors of the gastrointestinal tract. About 85% carry an activating mutation in the <it>KIT </it>or <it>PDGFRA </it>gene. Approximately 10% of GIST are so-called wild type GIST (wt-GIST) without mutations in the hot spots. In the present study we evaluated appropriate reference genes for the expression analysis of formalin-fixed, paraffin-embedded and fresh frozen samples from gastrointestinal stromal tumors. We evaluated the gene expression of <it>KIT </it>as well as of the alternative receptor tyrosine kinase genes <it>FLT3</it>, <it>CSF1-R</it>, <it>PDGFRB</it>, <it>AXL </it>and <it>MET </it>by qPCR. wt-GIST were compared to samples with mutations in <it>KIT </it>exon 9 and 11 and <it>PDGFRA </it>exon 18 in order to evaluate whether overexpression of these alternative RTK might contribute to the pathogenesis of wt-GIST.</p> <p>Results</p> <p>Gene expression variability of the pooled cDNA samples is much lower than the single reverse transcription cDNA synthesis. By combining the lowest variability values of fixed and fresh tissue, the genes <it>POLR2A</it>, <it>PPIA</it>, <it>RPLPO </it>and <it>TFRC </it>were chosen for further analysis of the GIST samples. Overexpression of <it>KIT </it>compared to the corresponding normal tissue was detected in each GIST subgroup except in GIST with <it>PDGFRA </it>exon 18 mutation. Comparing our sample groups, no significant differences in the gene expression levels of <it>FLT3</it>, <it>CSF1R </it>and <it>AXL </it>were determined. An exception was the sample group with <it>KIT </it>exon 9 mutation. A significantly reduced expression of <it>CSF1R</it>, <it>FLT3 </it>and <it>PDGFRB </it>compared to the normal tissue was detected. GIST with mutations in <it>KIT </it>exon 9 and 11 and in <it>PDGFRA </it>exon 18 showed a significant <it>PDGFRB </it>downregulation.</p> <p>Conclusions</p> <p>As the variability of expression levels for the reference genes is very high comparing fresh frozen and formalin-fixed tissue there is a strong need for validation in each tissue type. None of the alternative receptor tyrosine kinases analyzed is associated with the pathogenesis of wild-type or mutated GIST. It remains to be clarified whether an autocrine or paracrine mechanism by overexpression of receptor tyrosine kinase ligands is responsible for the tumorigenesis of wt-GIST.</p
Dissecting the knee - Air shower measurements with KASCADE
Recent results of the KASCADE air shower experiment are presented in order to
shed some light on the astrophysics of cosmic rays in the region of the knee in
the energy spectrum. The results include investigations of high-energy
interactions in the atmosphere, the analysis of the arrival directions of
cosmic rays, the determination of the mean logarithmic mass, and the unfolding
of energy spectra for elemental groups
Cosmic Ray Energy Spectra and Mass Composition at the Knee - Recent Results from KASCADE -
Recent results from the KASCADE experiment on measurements of cosmic rays in
the energy range of the knee are presented. Emphasis is placed on energy
spectra of individual mass groups as obtained from an two-dimensional unfolding
applied to the reconstructed electron and truncated muon numbers of each
individual EAS. The data show a knee-like structure in the energy spectra of
light primaries (p, He, C) and an increasing dominance of heavy ones (A > 20)
towards higher energies. This basic result is robust against uncertainties of
the applied interaction models QGSJET and SIBYLL which are used in the shower
simulations to analyse the data. Slight differences observed between
experimental data and EAS simulations provide important clues for further
improvements of the interaction models. The data are complemented by new limits
on global anisotropies in the arrival directions of CRs and by upper limits on
point sources. Astrophysical implications for discriminating models of maximum
acceleration energy vs galactic diffusion/drift models of the knee are
discussed based on this data.Comment: 8 pages, 7 figures, to appear in Nuclear Physics B, Proceedings
Supplements, as part of the volume for the CRIS 2004, Cosmic Ray
International Seminar: GZK and Surrounding
Expression of cell cycle regulators and frequency of TP53 mutations in high risk gastrointestinal stromal tumors prior to adjuvant imatinib treatment
Despite of multitude investigations no reliable prognostic immunohistochemical biomarkers in GIST have been established so far with added value to predict the recurrence risk of high risk GIST besides mitotic count, primary location and size. In this study, we analyzed the prognostic relevance of eight cell cycle and apoptosis modulators and of TP53 mutations for prognosis in GIST with high risk of recurrence prior to adjuvant treatment with imatinib. In total, 400 patients with high risk for GIST recurrence were randomly assigned for adjuvant imatinib either for one or for three years following laparotomy. 320 primary tumor samples with available tumor tissue were immunohistochemically analyzed prior to treatment for the expression of cell cycle regulators and apoptosis modulators cyclin D1, p21, p16, CDK4, E2F1, MDM2, p53 and p-RB1. TP53 mutational analysis was possible in 245 cases. A high expression of CDK4 was observed in 32.8% of all cases and was associated with a favorable recurrence free survival (RFS), whereas high expression of MDM2 (12.2%) or p53 (35.3%) was associated with a shorter RFS. These results were independent from the primary KIT or PDGFRA mutation. In GISTs with higher mitotic counts was a significantly increased expression of cyclin D1, p53 and E2F1. The expression of p16 and E2F1 significantly correlated to a non-gastric localization. Furthermore, we observed a significant higher expression of p21 and E2F1 in KIT mutant GISTs compared to PDGFRA mutant and wt GISTs. The overall frequency of TP53 mutations was low (n = 8; 3.5%) and could not be predicted by the immunohistochemical expression of p53. In summary, mutation analysis in TP53 plays a minor role in the subgroup of high-risk GIST before adjuvant treatment with imatinib. Strong expression of MDM2 and p53 correlated with a shorter recurrence free survival, whereas a strong expression of CDK4 correlated to a better recurrence free survival.Peer reviewe
Entanglement and correlation in anisotropic quantum spin systems
Analytical expressions for the entanglement measures concurrence,
i-concurrence and 3-tangle in terms of spin correlation functions are derived
using general symmetries of the quantum spin system. These relations are
exploited for the one-dimensional XXZ-model, in particular the concurrence and
the critical temperature for disentanglement are calculated for finite systems
with up to six qubits. A recent NMR quantum error correction experiment is
analyzed within the framework of the proposed theoretical approach.Comment: 8 pages, 3 figure
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