Showing papers by "Humboldt University of Berlin published in 2005"

Working memory span tasks: A methodological review and user’s guide

Abstract: Working memory (WM) span tasks—and in particular, counting span, operation span, and reading span tasks—are widely used measures of WM capacity. Despite their popularity, however, there has never been a comprehensive analysis of the merits of WM span tasks as measurement tools. Here, we review the genesis of these tasks and discuss how and why they came to be so influential. In so doing, we address the reliability and validity of the tasks, and we consider more technical aspects of the tasks, such as optimal administration and scoring procedures. Finally, we discuss statistical and methodological techniques that have commonly been used in conjunction with WM span tasks, such as latent variable analysis and extreme-groups designs.

Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL): A consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis

Abstract: We undertook this study to develop uniformly accepted criteria for the definition of organ involvement and response for patients on treatment protocols for immunoglobulin light-chain amyloidosis (AL). A consensus panel was convened comprising 13 specialists actively involved in the treatment of patients with amyloidosis. Institutional criteria were submitted from each, and a consensus was developed defining each organ involved and the criteria for response. Specific criteria have been developed with agreed on definitions of organ and hematologic response as a result of discussions at the 10th International Symposium on Amyloid and Amyloidosis held in Tours, France, April 2004. These criteria now form the working definition of involvement and response for the purposes of future data collection and reporting. We report criteria that centers can now use to define organ involvement and uniform response criteria for reporting outcomes in patients with light-chain AL.

The Topological Vertex

Abstract: We construct a cubic field theory which provides all genus amplitudes of the topological A-model for all non-compact toric Calabi-Yau threefolds. The topology of a given Feynman diagram encodes the topology of a fixed Calabi-Yau, with Schwinger parameters playing the role of Kahler classes of the threefold. We interpret this result as an operatorial computation of the amplitudes in the B-model mirror which is the quantum Kodaira-Spencer theory. The only degree of freedom of this theory is an unconventional chiral scalar on a Riemann surface. In this setup we identify the B-branes on the mirror Riemann surface as fermions related to the chiral boson by bosonization.

Central nervous system injury-induced immune deficiency syndrome

Abstract: Infections are a leading cause of morbidity and mortality in patients with acute CNS injury. It has recently become clear that CNS injury significantly increases susceptibility to infection by brain-specific mechanisms: CNS injury induces a disturbance of the normally well balanced interplay between the immune system and the CNS. As a result, CNS injury leads to secondary immunodeficiency - CNS injury-induced immunodepression (CIDS) - and infection. CIDS might serve as a model for the study of the mechanisms and mediators of brain control over immunity. More importantly, understanding CIDS will allow us to work on developing effective therapeutic strategies, with which the outcome after CNS damage by a host of diseases could be improved by eliminating a major determinant of poor recovery.

Experimental autoimmune encephalomyelitis repressed by microglial paralysis.

Abstract: Although microglial activation occurs in inflammatory, degenerative and neoplastic central nervous system (CNS) disorders, its role in pathogenesis is unclear. We studied this question by generating CD11b-HSVTK transgenic mice, which express herpes simplex thymidine kinase in macrophages and microglia. Ganciclovir treatment of organotypic brain slice cultures derived from CD11b-HSVTK mice abolished microglial release of nitrite, proinflammatory cytokines and chemokines. Systemic ganciclovir administration to CD11b-HSVTK mice elicited hematopoietic toxicity, which was prevented by transfer of wild-type bone marrow. In bone marrow chimeras, ganciclovir blocked microglial activation in the facial nucleus upon axotomy and repressed the development of experimental autoimmune encephalomyelitis. We conclude that microglial paralysis inhibits the development and maintenance of inflammatory CNS lesions. The microglial compartment thus provides a potential therapeutic target in inflammatory CNS disorders. These results validate CD11b-HSVTK mice as a tool to study the impact of microglial activation on CNS diseases in vivo.

Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious disease

Abstract: Summary Toll-like receptors (TLRs) play an important part in the innate immune recognition of invading microorganisms, initiating sufficient immune responses. Growing amounts of data suggest that the ability of certain individuals to respond properly to TLR ligands may be impaired by single nucleotide polymorphisms (SNPs) within TLR genes, resulting in an altered susceptibility to, or course of, infectious or inflammatory disease. Most studies have focused on two cosegregating SNPs—Asp299Gly and Thr399Ile—within the gene encoding TLR4, the receptor for bacterial lipopolysaccharide. These SNPs are present in approximately 10% of white individuals, and have been found to be positively correlated with several infectious diseases. However, these SNPs seem to protect from atherosclerosis and related diseases, which is reviewed in this article also. Meanwhile, SNPs of genes encoding other TLRs—eg, TLR2, which recognises a wide variety of microbial ligands—have been reported, and preliminary studies indicate an impact on susceptibility to infectious and inflammatory diseases as well. This review summarises and discusses the results obtained, and draws conclusions from these data.

Fast noninvasive activation and inhibition of neural and network activity by vertebrate rhodopsin and green algae channelrhodopsin.

Abstract: Techniques for fast noninvasive control of neuronal excitability will be of major importance for analyzing and understanding neuronal networks and animal behavior. To develop these tools we demonstrated that two light-activated signaling proteins, vertebrate rat rhodopsin 4 (RO4) and the green algae channelrhodospin 2 (ChR2), could be used to control neuronal excitability and modulate synaptic transmission. Vertebrate rhodopsin couples to the Gi/o, pertussis toxin-sensitive pathway to allow modulation of G protein-gated inward rectifying potassium channels and voltage-gated Ca2+ channels. Light-mediated activation of RO4 in cultured hippocampal neurons reduces neuronal firing within ms by hyperpolarization of the somato-dendritic membrane and when activated at presynaptic sites modulates synaptic transmission and paired-pulse facilitation. In contrast, somato-dendritic activation of ChR2 depolarizes neurons sufficiently to induce immediate action potentials, which precisely follow the ChR2 activation up to light stimulation frequencies of 20 Hz. To demonstrate that these constructs are useful for regulating network behavior in intact organisms, embryonic chick spinal cords were electroporated with either construct, allowing the frequency of episodes of spontaneous bursting activity, known to be important for motor circuit formation, to be precisely controlled. Thus light-activated vertebrate RO4 and green algae ChR2 allow the antagonistic control of neuronal function within ms to s in a precise, reversible, and noninvasive manner in cultured neurons and intact vertebrate spinal cords.

Involvement of Foxo transcription factors in angiogenesis and postnatal neovascularization

Abstract: Forkhead box O (Foxo) transcription factors are emerging as critical transcriptional integrators among pathways regulating differentiation, proliferation, and survival, yet the role of the distinct Foxo family members in angiogenic activity of endothelial cells and postnatal vessel formation has not been studied. Here, we show that Foxo1 and Foxo3a are the most abundant Foxo isoforms in mature endothelial cells and that overexpression of constitutively active Foxo1 or Foxo3a, but not Foxo4, significantly inhibits endothelial cell migration and tube formation in vitro. Silencing of either Foxo1 or Foxo3a gene expression led to a profound increase in the migratory and sprout-forming capacity of endothelial cells. Gene expression profiling showed that Foxo1 and Foxo3a specifically regulate a nonredundant but overlapping set of angiogenesis- and vascular remodeling–related genes. Whereas angiopoietin 2 (Ang2) was exclusively regulated by Foxo1, eNOS, which is essential for postnatal neovascularization, was regulated by Foxo1 and Foxo3a. Consistent with these findings, constitutively active Foxo1 and Foxo3a repressed eNOS protein expression and bound to the eNOS promoter. In vivo, Foxo3a deficiency increased eNOS expression and enhanced postnatal vessel formation and maturation. Thus, our data suggest an important role for Foxo transcription factors in the regulation of vessel formation in the adult.

Privacy in e-commerce: stated preferences vs. actual behavior

Abstract: In times of ubiquitous electronic communication and increasing industry pressure for standard electronic authentication, the maintenance of privacy, or "the right to be left alone" becomes a subject of increasing concern. The possibility of a "transparent human," whose vital information is up for grabs, can most easily be envisioned in the realm of e-commerce, due in part to the large amounts of data available, and in part to the high payoffs expected from using this data for marketing purposes.

Integrative model of the response of yeast to osmotic shock

Abstract: Integration of experimental studies with mathematical modeling allows insight into systems properties, prediction of perturbation effects and generation of hypotheses for further research. We present a comprehensive mathematical description of the cellular response of yeast to hyperosmotic shock. The model integrates a biochemical reaction network comprising receptor stimulation, mitogen-activated protein kinase cascade dynamics, activation of gene expression and adaptation of cellular metabolism with a thermodynamic description of volume regulation and osmotic pressure. Simulations agree well with experimental results obtained under different stress conditions or with specific mutants. The model is predictive since it suggests previously unrecognized features of the system with respect to osmolyte accumulation and feedback control, as confirmed with experiments. The mathematical description presented is a valuable tool for future studies on osmoregulation in yeast and—with appropriate modifications—other organisms. It also serves as a starting point for a comprehensive description of cellular signaling.

Conditional and Dynamic Convex Risk Measures

Abstract: We extend the definition of a convex risk measure to a conditional framework where additional information is available. We characterize these risk measures through the associated acceptance sets and prove a representation result in terms of conditional expectations. A suitable regularity property of conditional risk measures is defined and discussed. Finally, we introduce the concept of a dynamic convex risk measure as a family of successive conditional convex risk measures and characterize those satisfying some natural time consistency properties. As a reference example, illustrating all the proposed developments, we introduce a suitably defined dynamic version of the class of entropic risk measures.

Safety analyses of adalimumab (HUMIRA) in global clinical trials and US postmarketing surveillance of patients with rheumatoid arthritis

Abstract: Objective: To assess the safety of adalimumab in global clinical trials and postmarketing surveillance among patients with rheumatoid arthritis (RA). Methods: Safety data for adalimumab treated patients from randomised controlled trials, open label extensions, and two phase IIIb open label trials were analysed. In addition, postmarketing spontaneous reports of adverse events in the United States were collected following Food and Drug Administration approval of adalimumab on 31 December 2002. Results: As of 15 April 2005, the RA clinical trial safety database analysed covered 10 050 patients, representing 12 506 patient-years (PYs) of adalimumab exposure. The rate of serious infections, 5.1/100 PYs, was comparable to that reported on 31 August 2002 (4.9/100 PYs), and to published reports of RA populations naive to anti-tumour necrosis factor (TNF) therapy. Following implementation of tuberculosis (TB) screening in clinical trials, the rate of TB decreased. There were 34 cases of TB as of this analysis (0.27/100 PYs). The standardised incidence ratio for lymphoma was 3.19 (95% CI 1.78 to 5.26), consistent with the observed increased incidence in the general RA population. As of 30 June 2005, there were an estimated 78 522 PYs of exposure to adalimumab in the US postmarketing period. Seventeen TB cases were spontaneously reported (0.02/100 PYs) from the US. Rates of other postmarketing events of interest, such as congestive heart failure, systemic lupus erythematosus, opportunistic infections, blood dyscrasias, lymphomas, and demyelinating disease, support observations from clinical trials. Conclusion: Analyses of these data demonstrate that long term adalimumab treatment is generally safe and well tolerated in patients with RA.

Discovery of very high energy gamma rays associated with an x-ray binary.

Abstract: X-ray binaries are composed of a normal star in orbit around a neutron star or stellar-mass black hole. Radio and x-ray observations have led to the presumption that some x-ray binaries called microquasars behave as scaled-down active galactic nuclei. Microquasars have resolved radio emission that is thought to arise from a relativistic outflow akin to active galactic nuclei jets, in which particles can be accelerated to large energies. Very high energy γ-rays produced by the interactions of these particles have been observed from several active galactic nuclei. Using the High Energy Stereoscopic System, we find evidence for gamma-ray emission of >100 gigaelectron volts from a candidate microquasar, LS 5039, showing that particles are also accelerated to very high energies in these systems.

Dopamine depletion increases the power and coherence of beta-oscillations in the cerebral cortex and subthalamic nucleus of the awake rat.

Abstract: Local field potentials (LFPs) recorded from the subthalamic nucleus (STN) of untreated patients implanted with stimulation electrodes for the treatment of Parkinson's disease (PD) demonstrate strong coherence with the cortical electroencephalogram over the beta-frequency range (15-30 Hz). However, studies in animal models of PD emphasize increased temporal coupling in cortico-basal ganglia circuits at substantially lower frequencies, undermining the potential usefulness of these models. Here we show that 6-hydroxydopamine (6-OHDA) lesions of midbrain dopamine neurons are associated with significant increases in the power and coherence of beta-frequency oscillatory activity present in LFPs recorded from frontal cortex and STN of awake rats, as compared with the healthy animal. Thus, the pattern of synchronization between population activity in the STN and cortex in the 6-OHDA-lesioned rodent model of PD closely parallels that seen in the parkinsonian human. The peak frequency of coherent activity in the beta-frequency range was increased in lesioned animals during periods of spontaneous and sustained movement. Furthermore, administration of the dopamine receptor agonist apomorphine to lesioned animals suppressed beta-frequency oscillations, and increased coherent activity at higher frequencies in the cortex and STN, before producing the rotational behaviour indicative of successful lesion. Taken together, these results support a crucial role for dopamine in the modulation of population activity in cortico-basal ganglia circuits, whereby dopaminergic mechanisms effectively filter out synchronized, rhythmic activity at beta-frequencies at the systems level, and shift temporal couplings in these circuits to higher frequencies. These changes may be important in regulating movement.

Working Memory and Intelligence—Their Correlation and Their Relation: Comment on Ackerman, Beier, and Boyle (2005)

Abstract: Onthebasisofameta-analysisofpairwisecorrelationsbetweenwork- ing memory tasks and cognitive ability measures, P. L. Ackerman, M. E. Beier, and M. O. Boyle (2005) claimed that working memory capacity (WMC) shares less than 25% of its variance with general intelligence (g) and with reasoning ability. In this comment, the authors argue that this is an underestimation because of several methodological shortcomings and biases. A reanalysis of the data reported in Ack- erman et al. using the correct statistical procedures demonstrates that g and WMC are very highly correlated. On a conceptual level, the authors point out that WMC should be regarded as an explanatory construct for intellectual abilities. Theories of working memory do not claim that WMC is isomorphic with intelligence factors but that it is a very strong predictor of reasoning ability and also predicts general fluid intelligence and g.

Discovery of the Binary Pulsar PSR B1259-63 in Very-High-Energy Gamma Rays around Periastron with H.E.S.S

Abstract: We report the discovery of very-high-energy (VHE) γ-ray emission of the binary system PSR B1259−63/SS 2883 of a radio pulsar orbiting a massive, luminous Be star in a highly eccentric orbit. The observations around the 2004 periastron passage of the pulsar were performed with the four 13 m Cherenkov telescopes of the HESS experiment, recently installed in Namibia and in full operation since December 2003. Between February and June 2004, a γ-ray signal from the binary system was detected with a total significance above 13σ. The flux was found to vary significantly on timescales of days which makes PSR B1259−63 the first variable galactic source of VHE γ-rays observed so far. Strong emission signals were observed in pre- and post-periastron phases with a flux minimum around periastron, followed by a gradual flux decrease in the months after. The measured time-averaged energy spectrum above a mean threshold energy of 380 GeV can be fitted by a simple power law F0(E/ 1T eV) −Γ with a photon index Γ= 2.7 ± 0.2stat ± 0.2sys and flux normalisation F0 = (1.3 ± 0.1stat ± 0.3sys) × 10 −12 TeV −1 cm −2 s −1 .T his detection of VHE γ-rays provides unambiguous evidence for particle acceleration to multi-TeV energies in the binary system. In combination with coeval observations of the X-ray synchrotron emission by the RXTE and INTEGRAL instruments, and assuming the VHE γ-ray emission to be produced by the inverse Compton mechanism, the magnetic field strength can be directly estimated to be of the order of 1 G.

High-throughput generation of small antibacterial peptides with improved activity.

Abstract: Cationic antimicrobial peptides are able to kill a broad variety of Gram-negative and Gram positive bacteria and thus are good candidates for a new generation of antibiotics to treat multidrug-resistant bacteria. Here we describe a high-throughput method to screen large numbers of peptides for improved antimicrobial activity. The method relies on peptide synthesis on a cellulose support and a Pseudomonas aeruginosa strain that constitutively expresses bacterial luciferase. A complete substitution library of 12-amino-acid peptides based on a linearized variant (RLARIVVIRVAR-NH(2)) of the bovine peptide bactenecin was screened and used to determine which substitutions at each position of the peptide chain improved activity. By combining the most favorable substitutions, we designed optimized 12-mer peptides showing broad spectrum activities with minimal inhibitory concentrations (MIC) as low as 0.5 microg/ml against Escherichia coli. Similarly, we generated an 8-mer substituted peptide that showed broad spectrum activity, with an MIC of 2 microg/ml, against E. coli and Staphylococcus aureus.

From diffusion to anomalous diffusion: A century after Einstein’s Brownian motion

Abstract: Einstein’s explanation of Brownian motion provided one of the cornerstones which underlie the modern approaches to stochastic processes. His approach is based on a random walk picture and is valid for Markovian processes lacking long-term memory. The coarse-grained behavior of such processes is described by the diffusion equation. However, many natural processes do not possess the Markovian property and exhibit anomalous diffusion. We consider here the case of subdiffusive processes, which correspond to continuous-time random walks in which the waiting time for a step is given by a probability distribution with a diverging mean value. Such a process can be considered as a process subordinated to normal diffusion under operational time which depends on this pathological waiting-time distribution. We derive two different but equivalent forms of kinetic equations, which reduce to known fractional diffusion or Fokker–Planck equations for waiting-time distributions following a power law. For waiting time distributions which are not pure power laws one or the other form of the kinetic equation is advantageous, depending on whether the process slows down or accelerates in the course of time.

Slow feature analysis yields a rich repertoire of complex cell properties.

Abstract: In this study we investigate temporal slowness as a learning principle for receptive fields using slow feature analysis, a new algorithm to determine functions that extract slowly varying signals from the input data. We find a good qualitative and quantitative match between the set of learned functions trained on image sequences and the population of complex cells in the primary visual cortex (V1). The functions show many properties found also experimentally in complex cells, such as direction selectivity, non-orthogonal inhibition, end-inhibition, and side-inhibition. Our results demonstrate that a single unsupervised learning principle can account for such a rich repertoire of receptive field properties.

Social Innovation and Civil Society in Urban Governance: Strategies for an Inclusive City

Abstract: Processes of socioeconomic polarisation and social exclusion mark contemporary cities. In many countries, welfare states are in crisis, suffering from post-Fordist transformations. In cities, new ways of governance are needed to overcome the consequences of economic, social and political restructuring. This article seeks to explore the role of civil society in new urban governance arrangements that will hopefully contribute to counter the trends towards social exclusion. While aware of the ambiguity of civil society's role in rebuilding governance relationships, it is argued that, under certain conditions, civil society is found to be a valuable contributor towards more cohesive cities and governance arrangements that promote them. Such conditions involve the existence of a multiscalar democratic governance regime that favours public deliberation and social economy initiatives.

WHO/EORTC classification of cutaneous lymphomas 2005: histological and molecular aspects.

Abstract: The new WHO/EORTC classification for cutaneous lymphomas comprises mature T-cell and natural killer (NK)-cell neoplasms, mature B-cell neoplasms, and immature hematopoietic malignancies. It reflects the unique features of lymphoproliferative diseases of the skin, and at the same time it is as compatible as possible with the concepts underlying the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. This article reviews the histological, phenotypical, and molecular genetic features of the various nosological entities included in this new classification. These findings always have to be interpreted in the context of the clinical features and biologic behavior

Transforming BPEL to petri nets

Abstract: We present a Petri net semantics for the Business Process Execution Language for Web Services (BPEL) Our semantics covers the standard behaviour of BPEL as well as the exceptional behaviour (eg faults, events, compensation) The semantics is implemented as a parser that translates BPEL specifications into the input language of the Petri net model checking tool LoLA We demonstrate that the semantics is well suited for computer aided verification purposes

Imputation Rules to Improve the Education Variable in the Iab Employment Subsample

Abstract: The education variable in the IAB employment subsample has two shortcomings: missing values and inconsistencies with the reporting rule We propose several deductive imputation procedures to improve the variable They mainly use the multiple education information available in the data because the employees' education is reported at least once a year We compare the improved data from the different procedures and the original data in typical applications in labor economics: educational composition of employment, wage inequality, and wage regression We find, that correcting the education variable: (i) shows the educational attainment of the male labor force to be higher than measured with the original data, (ii) gives different values for some measures of wage inequality, and (iii) does not change the estimates in wage regressions much