Networks : On the relation of bi- and multivariate measures

Date of Acceptance: 28/04/2015 Acknowledgement The article processing charge was funded by the German Research Foundation (DFG) and the Albert Ludwigs University Freiburg in the funding programme Open Access PublishingPeer reviewedPublisher PD

A numerically efficient implementation of the expectation maximization algorithm for state space models

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Assessing the strength of directed influences among neural signals : An approach to noisy data

Acknowledgements This work was supported by the German Science Foundation (Ti315/4-2), the German Federal Ministry of Education and Research (BMBF grant 01GQ0420), and the Excellence Initiative of the German Federal and State Governments. B.S. is indebted to the Kosterlitz Centre for the financial support of this research project.Peer reviewedPreprin

Investigation of the applicability of Cu–Fe–Mn–Ni based high entropy and compositionally complex alloys as metal matrix composites for cobalt free hot-pressed diamond tools

Due to the rising demand and carcinogenic effect of cobalt, alternative metal matrixes need to be developed for hot-pressed diamond tools. Due to this reason High-Entropy alloys without cobalt were calculated via phase fraction diagrams. Three alloys of the Al–Cu–Fe–Mn–Ni system Al30Cu30Fe5Mn25Ni10, Al11.25Cu35Fe5Mn20Ni28.75 and Al5Cu20Fe25Mn25Ni25 were chosen due to their different crystal structures ranging from pure bcc, eutectic fcc-bcc to pure fcc crystal structure. Cr5Cu20Fe25Mn25Ni25 was chosen to verify the change of one element on the consolidation properties. The alloys were mechanically alloyed and hot-pressed at 800 °C for 3 min without and at 900 °C for 3 min with diamonds. Porosity increased with the fraction of bcc solid solution in the investigated alloys of the Al–Cu–Fe–Mn–Ni system. Samples consisting of Cr5Cu20Fe25Mn25Ni25 showed the lowest porosity, which was attributed to precipitation of a second copper-rich fcc solid solution around the remaining pores. At a process temperature of 800 °C and 3 min isothermal hold the samples featured a porosity of only 2.72%. Within the XRD patterns and SEM images of the hot-pressed samples with diamonds no graphitization or formation of carbides could be observed. Therefore, Cr5Cu20Fe25Mn25Ni25 was identified as a promising cobalt free metal-matrix candidate for diamond tools

Application of the eutectic high entropy alloy Nb0.73CoCrFeNi2.1 for high temperature joints

The eutectic high entropy alloy Nb0.73CoCrFeNi2.1 was manufactured by means of arc smelting and the obtained ingots were cut into 300-μm-thick foils, which were used as filler alloys to braze Crofer 22 APU to Hf-metallized yttria-stabilized zirconia (3YSZ). The brazing process was conducted in a vacuum furnace at 1200 °C for 5 min at a vacuum of 4.3·10–4 mbar. In order to minimize the intense diffusion and erosion of the steel substrate, a heating and cooling rate of 50 K/min was applied. Sound joints without any pores or flaws were obtained. The microstructure of the joints consisted of an HfO2 reaction layer at the ceramic interface and the same eutectic structure consisting of a Laves phase and a solid solution that was already detected in the smelted foil. The average hardness of the microstructure in the joint seam amounted to 352 ± 17 HV0.01 and the joints reached strength values up to 97 ± 7 MPa while the fracture area was always located at the ceramic interface in the HfO2 layer. Comparable joints, with AgCuTi3 as filler metal, brazed at 920 °C, only reached a shear strength of ~ 52 ± 2 MPa

Dynamic Modeling, Parameter Estimation, and Uncertainty Analysis in R

In a wide variety of research fields, dynamic modeling is employed as an instrument to learn and understand complex systems. The differential equations involved in this process are usually non-linear and depend on many parameters whose values determine the characteristics of the emergent system. The inverse problem, i.e., the inference or estimation of parameter values from observed data, is of interest from two points of view. First, the existence point of view, dealing with the question whether the system is able to reproduce the observed dynamics for any parameter values. Second, the identifiability point of view, investigating invariance of the prediction under change of parameter values, as well as the quantification of parameter uncertainty. In this paper, we present the R package dMod providing a framework for dealing with the inverse problem in dynamic systems modeled by ordinary differential equations. The uniqueness of the approach taken by dMod is to provide and propagate accurate derivatives computed from symbolic expressions wherever possible. This derivative information highly supports the convergence of optimization routines and enhances their numerical stability, a requirement for the applicability of sophisticated uncertainty analysis methods. Computational efficiency is achieved by automatic generation and execution of C code. The framework is object-oriented (S3) and provides a variety of functions to set up ordinary differential equation models, observation functions and parameter transformations for multi-conditional parameter estimation. The key elements of the framework and the methodology implemented in dMod are highlighted by an application on a three-compartment transporter model

Zebrafish Pou5f1-dependent transcriptional networks in temporal control of early development

Time-resolved transcriptome analysis of early pou5f1 mutant zebrafish embryos identified groups of developmental regulators, including SoxB1 genes, that depend on Pou5f1 activity, and a large cluster of differentiation genes which are prematurely expressed.Pou5f1 represses differentiation genes indirectly via activation of germlayer-specific transcriptional repressor genes, including her3, which may mediate in part Pou5f1-dependent repression of neural genes.A dynamic mathematical model is established for Pou5f1 and SoxB1 activity-dependent temporal behaviour of downstream transcriptional regulatory networks. The model predicts that Pou5f1-dependent increase in SoxB1 activity significantly contributes to developmental timing in the early gastrula.Comparison to mouse Pou5f1/Oct4 reveals evolutionary conserved targets. We show that Pou5f1 developmental function is also conserved by demonstrating rescue of Pou5f1 mutant zebrafish embryos by mouse POU5F1/OCT4

Network modulation during complex syntactic processing

Complex sentence processing is supported by a left-lateralized network including inferior frontal cortex and posterior superior temporal cortex. This study investigates the pattern of connectivity and information flow within this network. We used fMRI BOLD data derived from 12 healthy participants reported in and earlier study (Thompson, C. K., Den Ouden, D. B., Bonakdarpour, B., Garibaldi, K. & Parrish, T. B. (2010b). Neural plasticity and treatment-induced recovery of sentence processing in agrammatism. Neuropsychologia, 48(11), 3211-3227) to identify activation peaks associated with object-cleft over syntactically less complex subject-cleft processing. Directed Partial Correlation Analysis was conducted on time series extracted from participant-specific activation peaks and showed evidence of functional connectivity between four regions, linearly between premotor cortex, inferior frontal gyrus, posterior superior temporal sulcus and anterior middle temporal gyrus. This pattern served as the basis for Dynamic Causal Modeling of networks with a driving input to posterior superior temporal cortex, which likely supports thematic role assignment, and networks with a driving input to inferior frontal cortex, a core region associated with syntactic computation. The optimal model was determined through both frequentist and Bayesian model selection and turned out to reflect a network with a primary drive from inferior frontal cortex and modulation of the connection between inferior frontal and posterior superior temporal cortex by complex sentence processing. The winning model also showed a substantive role for a feedback mechanism from posterior superior temporal cortex back to inferior frontal cortex. We suggest that complex syntactic processing is driven by word-order analysis, supported by inferior frontal cortex, in an interactive relation with posterior superior temporal cortex, which supports verb argument structure processing

Allergen-induced asthmatic responses modified by a GATA3-specific DNAzyme

BACKGROUND : The most prevalent phenotype of asthma is characterized by eosinophil-dominated inflammation that is driven by a type 2 helper T cell (Th2). Therapeutic targeting of GATA3, an important transcription factor of the Th2 pathway, may be beneficial. We evaluated the safety and efficacy of SB010, a novel DNA enzyme (DNAzyme) that is able to cleave and inactivate GATA3 messenger RNA (mRNA). METHODS : We conducted a randomized, double-blind, placebo-controlled, multicenter clinical trial of SB010 involving patients who had allergic asthma with sputum eosinophilia and who also had biphasic early and late asthmatic responses after laboratory-based allergen provocation. A total of 40 patients could be evaluated; 21 were assigned to receive 10 mg of SB010, and 19 were assigned to receive placebo, with each study drug administered by means of inhalation once daily for 28 days. An allergen challenge was performed before and after the 28-day period. The primary end point was the late asthmatic response as quantified by the change in the area under the curve (AUC) for forced expiratory volume in 1 second (FEV1). RESULTS : After 28 days, SB010 attenuated the mean late asthmatic response by 34%, as compared with the baseline response, according to the AUC for FEV1, whereas placebo was associated with a 1% increase in the AUC for FEV1 (P = 0.02). The early asthmatic response with SB010 was attenuated by 11% as measured by the AUC for FEV1, whereas the early response with placebo was increased by 10% (P = 0.03). Inhibition of the late asthmatic response by SB010 was associated with attenuation of allergen-induced sputum eosinophilia and with lower levels of tryptase in sputum and lower plasma levels of interleukin-5. Allergen-induced levels of fractional exhaled nitric oxide and airway hyperresponsiveness to methacholine were not affected by either SB010 or placebo. CONCLUSIONS : Treatment with SB010 significantly attenuated both late and early asthmatic responses after allergen provocation in patients with allergic asthma. Biomarker analysis showed an attenuation of Th2-regulated inflammatory responses

“A very orderly retreat”: Democratic transition in East Germany, 1989-90

East Germany's 1989-90 democratisation is among the best known of East European transitions, but does not lend itself to comparative analysis, due to the singular way in which political reform and democratic consolidation were subsumed by Germany's unification process. Yet aspects of East Germany's democratisation have proved amenable to comparative approaches. This article reviews the comparative literature that refers to East Germany, and finds a schism between those who designate East Germany's transition “regime collapse” and others who contend that it exemplifies “transition through extrication”. It inquires into the merits of each position and finds in favour of the latter. Drawing on primary and secondary literature, as well as archival and interview sources, it portrays a communist elite that was, to a large extent, prepared to adapt to changing circumstances and capable of learning from “reference states” such as Poland. Although East Germany was the Soviet state in which the positions of existing elites were most threatened by democratic transition, here too a surprising number succeeded in maintaining their position while filing across the bridge to market society. A concluding section outlines the alchemy through which their bureaucratic power was transmuted into property and influence in the “new Germany”